TW201233333A - Improved tolerance in a low calorie infant formula - Google Patents

Abstract

The present disclosure is directed to low calorie infant formulas, and in particular, low calorie infant formulas that have a low buffering capacity, exhibit an increased rate of protein hydrolysis and digestion, and have an improved tolerance, as compared to full calorie infant formulas. Also disclosed are low calorie liquid infant formulas that have a reduced (i.e., ''low'') micronutrient content on a per volume basis, and exhibit an overall improvement in the physical properties of the formula, as compared to low calorie liquid infant formulas having a higher micronutrient content.

Description

201233333 六、發明說明： 【發明所屬之技術領域】 本發明係關於低熱量嬰兒配方，且詳言之，與全熱量嬰 兒配方相比具有低緩衝能力、呈現增加之蛋白質水解及消 化率且具有改良之耐受性之低熱量嬰兒配方。亦揭示與具 有較高微量營養素含量之低熱量液體嬰兒配方相比具有降 低（亦即「低」）之以單位體積計之微量營養素含量且配方 之物理性質呈現整體改良（包括顏色較淺及穩定性改良）之 低熱置液體嬰兒配方。 本申凊案主張2010年12月30日申請之美國臨時申請案第 61/428,833號之權利，其揭示内容以全文引用的方式併入 本文中。 【先前技術】 存在多種類型之熟知且廣泛可用之嬰兒營養配方。該等 嬰兒配方包含多種經設計以滿足嬰兒生長之營養需要的營 養物，且通常包括脂肪、碳水化合物、蛋白質、維生素、 礦物質及其他有助於最佳化嬰兒生長及發育之營養物。 然而，通常認為母乳為新生兒之最佳營養源。已知人類 母乳向母乳餵養嬰兒提供優良免疫學利益。因此，大部分 嬰兒配方經設計以在組成及功能方面與母乳更接近。 亦已知人類母乳之組成在嬰兒分娩後最初數週内發生變 化。人類母乳在出生後最初5天期間稱為初乳在出生後 第6天至第Η天期間稱為過渡乳且隨後稱為成熟乳。在各 泌乳階段期間’相應人類母乳組成顯著不同。舉例而言， 161200.doc 201233333 初乳及過渡乳與成熟乳相比具有較低熱量密度以及較高蛋 白質及較低％水化合物濃度。三種定義之人乳分組中之維 生素及礦物質濃度亦不同》 一些市售嬰兒配方在組成上與成熟人類母乳類似但不相 同’且用於新生兒以及較大嬰兒。先前已公認新生兒之餵 養應以促進嬰兒生長為重點進行，且可藉由用具有與成熟 乳類似之營養物及能量含量之市售嬰兒配方餵養嬰兒來最 佳地實現該生長。 近來，已嘗試調配用於新生兒之具有較低能量含量且因 此與用習知全熱量嬰兒配方餵養提供之熱量相比在生命之 最初數週或數月期間提供較少熱量之嬰兒配方。先前對調 配具有低能量含量之嬰兒配方之嘗試涉及以單位體積計降 低或多種常量營養素（例如蛋白質、脂肪、碳水化合物） 之含量同時保持微量營養素含量與可見於全熱量嬰兒配方 中之含量類似。然而’常量營養素減少與高微量營養素之 組合可產生具有弱物理屬性之配方。舉例而言，該等配方 通常純較深，沈降問題增加且與全熱量配方相比在存放 期期間更易於分離。 此外些嬰兒配方餵養之新生兒可經歷腸胃道（GI)不 耐受性問冑，包括軟便、放屁及咳吐。Gig受性問題可 P刀地歸因於嬰兒之營養物（例如蛋白質）消化及吸收 為解決此不耐受性問題’一些嬰兒配方排除乳糖作 2分，而其他嬰兒配方則用水解蛋白置換完整乳蛋白以 '咸輕嬰兒消化系統負擔。 161200.doc 201233333 一些配方傲養之嬰兒與母乳餵養嬰兒相比亦可能經歷更 多的腸胃道感染事件。對此現象之一種解釋可為人類母乳 之緩衝能力較低。已知人類母乳與牛乳及以牛乳為基礎之 嬰兒配方相比具有較低酸緩衝性質。人類母乳之低緩衝能 力可使嬰兒之天然胃液酸度更有效使經口攝取之病原體失 活。 因此需要提供與先前已知的低熱量嬰兒配方相比具有改 良之物理屬性（諸如顏色較淺及穩定性改良）之低熱量液體 嬰兒配方。亦需要提供具有低緩衝能力（與母乳類似）且亦 具有增加之蛋白質水解及消化率及優良耐受性以提供嬰兒 其他利益之嬰兒配方。 【發明内容】 本發明係關於具有改良之物理屬性之低熱量液體嬰兒配 方。該等配方與具有較高微量營養素含量之低熱量液體嬰 兒配方相比具有降低（亦即「低」）之以單位體積計之微量 營養素含量且產品之物理性質呈現整體改良（包括顏色較 淺及穩定性改良）。亦揭示與習知全熱量嬰兒配方相比具 有低緩衝能力，呈現增加之蛋白質水解及消化率及/或具 有改良之配方耐受性的低熱量液體及粉末嬰兒配方。本發 明之低熱量配方在生命之最初數週期間投與新生兒時提供 充足的用於新生兒生長及發展之營養。 因此，在一個實施例中，本發明亦係關於改良嬰兒之嬰 兒配方耐交性之方法。該方法包含投與嬰兒具有約200至 小於600千卡/公升配方之能量含量的嬰兒配方。 161200.doc 201233333 在另一實施例中，本發明亦係關於改良嬰兒之嬰兒配方 耐受性之方法。該方法包含投與嬰兒低微量營養素嬰兒配 方，其包含微量營養素及至少一種選自由蛋白質、碳水化 合物、脂肪及其組合組成之群之常量營養素且具有約2〇〇 至小於600千卡/公升配方之能量含量。以單位體積計，至 少65%微量營養素以習知相應微量營養素量之約3〇%至約 80%之量包括於嬰兒配方中。 在另一實施例中’本發明亦係關於改良嬰兒之嬰兒配方 耐受性之方法◎該方法包含投與嬰兒低微量營養素嬰兒配 方’其包含微量營養素及至少―種選自由蛋白質、碳水化 合物、脂肪及其組合組成之群之常量營養素且具有約2〇〇 至約3 60千卡/公升配方之能量含量。以單位體積計，至少 45 /。微量營養素以習知相應微量營養素量之約3。至約 65%之量包括於嬰兒配方中。 在另實施例中’本發明亦係關於改良嬰兒之嬰兒配方 耐觉性之方法。該方法包含投與嬰兒低微量營養素嬰兒配 方，其包含微量營養素及至少一種選自由蛋白質、碳水化 合物、脂肪及其組合組成之群之常量營養素且具有約36〇 至小於600千卡/公升配方之能量含量。以單位體積計至 / 30/〇微量營養素以習知相應微量營養素量之約至約 80%之量包括於嬰兒配方中。 在另一實施例中，本發明係關於抑制嬰兒胃食道逆流之 方法。該方法包含投與嬰兒能量含量為約2〇〇至小於6〇〇千 卡/公升配方之嬰兒配方。 161200.doc • 6 · 201233333 在另一實施例中’本發明係關於抑制嬰兒胃食道逆流之 方法。該方法包含投與嬰兒低微量營養素嬰兒配方，其包 含微量營養素及至少一種選自由蛋白質、碳水化合物、脂 肪及其組合組成之群之常量營養素且具有約2〇〇至小於6〇〇 千卡/公升配方之能量含量。以單位體積計，至少6 5 %微量 營養素以習知相應微量營養素量之約3〇%至約8〇%之量包 括於嬰兒配方中。 在另一實施例中，本發明係關於抑制嬰兒胃食道逆流之 方法。該方法包含投與嬰兒低微量營養素嬰兒配方，其包 含微量營養素及至少—種選自由蛋白質、碳水化合物、脂 肪及其組合組成之群之常量營養素且具有約2〇〇至約360千 卡/公升配方之能量含量。以單位體積計，至少45%微量營 養素以習知相應微量營養素量之約3〇%至約65%之量包括 於嬰兒配方中。 在另一實施例中，本發明係關於抑制嬰兒胃食道逆流之 方法。該方法包含投與嬰兒低微量營養素嬰兒配方，其包 含微量營養素及至少—種選自由蛋白質、碳水化合物、脂 肪及其組合組成之群之常量營養素且具有約3 6〇至小於6〇〇 千卡/公升配方之能量含量。以單位體積計，至少3〇%微量 呂養素以$知相應微量營養素量之約55%至約之量包 括於嬰兒配方中。 現意外發現絲熱量配方中足夠量的—或多種微量營養 素以每千卡計而非以單位體積計與全熱量配方中之微量營 養素大體上匹配’則可調配具有改良之物理屬性之低熱量 161200.doc 201233333 液體嬰兒配方。因此該等配方與具有較高微量營養素含量 之低熱量液體嬰兒配方相比具有降低（亦即「低」）之以單 位體積計之微量營養素含量且產品之物理性質呈現整體改 良（包括顏色較淺及穩定性改良）。 亦發現低熱量液體或粉末嬰兒配方與習知全熱量嬰兒配 方相比具有較低緩衝能力’且在一些實施例中，其緩衝能 力低於人乳。因此本發明之低熱量嬰兒配方可用於調節嬰 兒之胃液酸度、減少嬰兒腸胃道中病原微生物生長及促進 有益微生物生長。亦發現本發明之低熱量嬰兒配方與習知 全熱量嬰兒配方相比呈現增加之蛋白質水解及消化率，且 因此具有改良之配方耐受性》 【實施方式】 本文中揭示之低熱量液體嬰兒配方與具有較高微量營養 素含量之習知嬰兒配方相比可具有低微量營養素含量（以 單位體積計）及改良之物理屬性。此外，本發明之方法利 用低熱量液體及粉末嬰兒配方調節嬰兒之胃液酸度，減少 嬰兒腸胃道中病原微生物生長且促進有益微生物生長，提 高蛋白質水解及消化率且改良配方耐受性。下文中詳細描 述本發明之嬰兒配方及方法之該等及其他及視情況可選特 徵以及一些多種其他視情況可選變化及添加。 本文中術語「殺菌釜（retort)」與「殺菌釜滅菌（ret〇rt sterilized)」可互換使用，且除非另有說明，否則係指用 營養液體（諸如液體嬰兒配方）填充容器（最通常為金屬罐或 其他類似封裝）且接著使填充有液體之封裝經歷必要加熱 161200.doc 201233333 滅菌步驟以形成殺菌蒼殺菌签·滅菌之營養液體產品之常用 操作。 本文中術語「無菌（aseptic)」與「無菌滅菌（aseptic sterilized)」可互換使用，且除非另有說明，否則係指不 依靠上述殺菌釜滅菌封裝步驟製造封裝產品，其中在填充 之前獨立地對營養液體及封裝進行滅菌，且接著在滅菌或 無菌加工條件下組合以形成經滅菌、無菌封裝之營養液體 產品。 如本文中所用術語「營養配方」或「營養產品」或 養組合物」可互換使用且除非另有說明，否則係指營養液 體、營養半液體、營養固體、營養半固體、營養粉末、營 養補充物及此項技術中已知的任何其他營養食品。營養固 體及粉末可經復原以形成營養液體，其均包含脂肪、蛋白 質及碳水化合物中之一或多者，且適用於由人類口服食 用。營養配方可包括嬰兒配方。 除非另有說明，否則如本文中所用術語「營養液體」係 指呈即飲型液體形式、濃縮形式之營養產品及藉由在使用 前復原本文中所描述之營養粉末產生之營養液體。 匕除非另有說明’否則如本文中所用術語「營養粉末」係 指呈可流動或可g取形式之營養產品，其可在食用前用水 種水性液體復原且包括噴霧乾燥及乾燥混合/乾燥 摻合粉末。 =另有說明，否則如本文中所用術語「營養半液體」 μ性質（諸如流動性質）介於液體與固體之間的形式，其 161200.doc 201233333 實例包括奶昔（thick shakes)及液體凝膠。 除非另有說明，否則如本文中所用術語「營養半固體」 係私性質（諸如剛性）介於固體與液體之間的形式，其實例 包括布丁、明膠及麵團。201233333 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a low-calorie infant formula, and in particular, has a low buffering capacity, exhibits increased protein hydrolysis and digestibility, and is improved compared to a full-calorie infant formula. Tolerant low calorie infant formula. It also reveals a reduced (ie, "low") micronutrient content per unit volume compared to a low calorie liquid infant formula with a higher micronutrient content and an overall improvement in the physical properties of the formulation (including lighter color and stability) Sexual improvement) low-calorie liquid infant formula. The present application claims the benefit of U.S. Provisional Application No. 61/428,833, filed on Dec. 30, 2010, the disclosure of which is hereby incorporated by reference. [Prior Art] There are many types of well-known and widely available infant nutrition formulas. These infant formulas contain a variety of nutrients designed to meet the nutritional needs of infant growth and typically include fats, carbohydrates, proteins, vitamins, minerals, and other nutrients that help optimize the growth and development of the baby. However, breast milk is generally considered to be the best source of nutrition for newborns. Human breast milk is known to provide excellent immunological benefits to breastfed infants. Therefore, most infant formulas are designed to be closer to breast milk in terms of composition and function. It is also known that the composition of human breast milk changes during the first few weeks after delivery of the baby. Human breast milk is called colostrum during the first 5 days after birth and is called transitional milk from day 6 to day after birth and is then called mature milk. The corresponding human breast milk composition was significantly different during each lactation phase. For example, 161200.doc 201233333 Colostrum and transition milk have lower caloric density and higher protein and lower % water compound concentrations than mature milk. The vitamins and mineral concentrations in the three defined human milk groups are also different. Some commercial infant formulas are similar in composition but different from mature human breast milk and are used in newborns and older infants. It has previously been recognized that feeding of newborns should be focused on promoting infant growth and that growth can be best achieved by feeding the infant with a commercial infant formula having nutrient and energy content similar to mature milk. Recently, attempts have been made to formulate infant formulas for newborns that have lower energy content and therefore provide less calories during the first weeks or months of life compared to the heat provided by conventional full calorie infant formula feeding. Previous attempts to formulate infant formulas with low energy content involved reducing the amount of macronutrients (e.g., protein, fat, carbohydrates) per unit volume while maintaining micronutrient levels similar to those found in whole calorie infant formulas. However, the combination of macronutrient reduction and high micronutrients produces formulations with weak physical properties. For example, such formulations are generally purely deep, have increased settling problems and are easier to separate during the shelf life than full heat formulations. In addition, infant formula-fed newborns can experience gastrointestinal intolerance (GI) intolerance, including soft stools, fart, and cough. Gig's sexual problems can be attributed to the digestion and absorption of nutrients (such as protein) in infants to solve this intolerance problem. Some infant formulas exclude lactose by 2 points, while other infant formulas are completely replaced with hydrolyzed proteins. Milk protein is burdened by the 'salty light infant's digestive system. 161200.doc 201233333 Some formula-raising babies may also experience more gastrointestinal infections than breast-fed babies. One explanation for this phenomenon is the low buffering capacity of human breast milk. Human breast milk is known to have lower acid buffering properties than cow's milk and infant formula based on cow's milk. The low buffering capacity of human breast milk allows the infant's natural gastric acidity to be more effective in inactivating pathogens that are orally ingested. There is therefore a need to provide a low calorie liquid infant formula having improved physical properties (such as lighter color and improved stability) than previously known low calorie infant formulas. It is also desirable to provide infant formulas that have low buffering capacity (similar to breast milk) and that also have increased protein hydrolysis and digestibility and excellent tolerance to provide other benefits to the infant. SUMMARY OF THE INVENTION The present invention is directed to a low calorie liquid infant formula having improved physical properties. These formulations have a reduced (ie, "low") micronutrient content per unit volume compared to a low calorie liquid infant formula with a higher micronutrient content and the overall physical properties of the product are improved (including lighter colors and Stability improvement). It also discloses low calorie liquid and powder infant formulas that have low buffering capacity, exhibit increased protein hydrolysis and digestibility, and/or improved formulation tolerance compared to conventional full calorie infant formulas. The low calorie formula of the present invention provides sufficient nutrients for the growth and development of the newborn during the first few weeks of life. Thus, in one embodiment, the invention is also directed to a method of improving the tolerance of infant formula in infants. The method comprises administering to an infant an infant formula having an energy content of from about 200 to less than 600 kcal/liter of formula. 161200.doc 201233333 In another embodiment, the invention is also directed to a method of improving the tolerance of an infant's infant formula. The method comprises administering to a baby low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, and having a formula of from about 2 to less than 600 kcal/liter Energy content. At least 65% of the micronutrients are included in the infant formula in an amount of from about 3% to about 80% by weight of the conventional micronutrient, per unit volume. In another embodiment, the invention is also directed to a method for improving infant formula tolerance in an infant. ◎ The method comprises administering to a baby a low micronutrient infant formula comprising micronutrients and at least one selected from the group consisting of proteins, carbohydrates, A macronutrient of a group of fats and combinations thereof having an energy content of from about 2 〇〇 to about 3 60 kcal/liter of formula. At least 45 / per unit volume. The micronutrients are about 3 times the amount of the corresponding micronutrients. Up to about 65% of the amount is included in the infant formula. In another embodiment, the invention is also directed to a method of improving the tolerance of an infant's infant formula. The method comprises administering an infant low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, and having a formulation of from about 36 〇 to less than 600 kcal/liter Energy content. The micronutrient per unit volume is included in the infant formula in an amount of from about 80% by weight of the conventional micronutrient. In another embodiment, the invention is directed to a method of inhibiting gastric esophageal reflux in a baby. The method comprises administering an infant formula having an infant energy content of from about 2 inches to less than 6 kilocalories per liter. 161200.doc • 6 · 201233333 In another embodiment, the present invention relates to a method of inhibiting gastric esophageal reflux in infants. The method comprises administering to an infant low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, and having from about 2 to less than 6 kcal/ The energy content of the liter formula. At least 65% of the micronutrients are included in the infant formula in an amount of from about 3% to about 8% by weight of the conventional micronutrient amount per unit volume. In another embodiment, the invention is directed to a method of inhibiting gastric esophageal reflux in a baby. The method comprises administering to an infant low micronutrient infant formula comprising micronutrients and at least one selected from the group consisting of macronutrients consisting of proteins, carbohydrates, fats, and combinations thereof, and having from about 2 to about 360 kcal per liter The energy content of the formula. At least 45% of the micronutrient is included in the infant formula in an amount of from about 3% to about 65% by weight of the conventional micronutrient, per unit volume. In another embodiment, the invention is directed to a method of inhibiting gastric esophageal reflux in a baby. The method comprises administering to an infant low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof, and having from about 36 to less than 6 kilocalories / liter formula energy content. At least 3% by weight of luciferin per unit volume is included in the infant formula in an amount of from about 55% to about the amount of the corresponding micronutrient. It has now been surprisingly found that a sufficient amount of the silk calorie formula - or multiple micronutrients to be substantially matched to the micronutrients in the full calorie formula per kilocalories rather than in unit volume - can be formulated with low calorie with improved physical properties 161200 .doc 201233333 Liquid infant formula. Therefore, these formulations have a reduced (ie, "low") micronutrient content per unit volume compared to a low calorie liquid infant formula with a higher micronutrient content and the overall physical properties of the product are improved (including lighter colors) And stability improvement). It has also been found that low calorie liquid or powder infant formulas have a lower buffering capacity' than in conventional full calorie infant formula' and in some embodiments, have a lower buffering capacity than human milk. Thus, the low calorie infant formula of the present invention can be used to adjust the gastric acidity of infants, reduce the growth of pathogenic microorganisms in the gastrointestinal tract of infants, and promote the growth of beneficial microorganisms. It has also been found that the low calorie infant formula of the present invention exhibits increased protein hydrolysis and digestibility compared to conventional full calorie infant formula, and thus has improved formulation tolerance. [Embodiment] The low calorie liquid infant formula disclosed herein has The conventional infant formula with higher micronutrient content can have a lower micronutrient content (in terms of unit volume) and improved physical properties. In addition, the method of the present invention utilizes a low-calorie liquid and powdered infant formula to adjust the gastric acidity of the infant, reduce the growth of pathogenic microorganisms in the gastrointestinal tract of the infant and promote the growth of beneficial microorganisms, improve protein hydrolysis and digestibility, and improve formulation tolerance. These and other and optionally optional features of the infant formula and method of the present invention, as well as a variety of other optional variations and additions, are described in detail below. The term "retort" and "ret〇rt sterilized" are used interchangeably herein and, unless otherwise indicated, are meant to fill a container with a nutrient liquid (such as a liquid infant formula) (most commonly A metal can or other similar package) and then subject the liquid-filled package to the usual operation of the sterilization process to form a sterilized sterilized sterilized nutritional liquid product. As used herein, the terms "aseptic" and "aseptic sterilized" are used interchangeably and, unless otherwise indicated, means that the packaged product is manufactured without relying on the sterilization sterilization step described above, wherein the individual is independently prior to filling. The nutritional liquids and packages are sterilized and then combined under sterile or aseptic processing conditions to form a sterilized, aseptically packaged nutritional liquid product. The terms "nutritional formula" or "nutritional product" or nutrient composition as used herein are used interchangeably and refer to nutrient liquids, nutrient semi-liquids, nutritive solids, nutrient semi-solids, nutrient powders, nutritional supplements, unless otherwise indicated. And any other nutritious food known in the art. The nutritional solids and powders can be reconstituted to form a nutritional liquid, each of which contains one or more of fats, proteins, and carbohydrates, and is suitable for oral consumption by humans. The nutritional formula can include an infant formula. The term "nutritional liquid" as used herein, unless otherwise indicated, refers to a ready-to-drink liquid form, a concentrated form of a nutritional product, and a nutritional liquid produced by restoring the nutritional powder described herein prior to use.匕 Unless otherwise stated, the term "nutritional powder" as used herein refers to a nutritional product in a flowable or removable form that can be reconstituted with an aqueous liquid prior to consumption and includes spray drying and dry mixing/drying. Powder. = otherwise stated, otherwise the term "nutrient semi-liquid" as used herein, μ property (such as flow properties) is between liquid and solid, 161200.doc 201233333 Examples include thick shakes and liquid gels . The term "nutrient semi-solid" as used herein, unless otherwise indicated, is a form in which the private property (such as rigidity) is between a solid and a liquid, examples of which include pudding, gelatin, and dough.

除非另有說明’否則如本文中所用術語「嬰兒」係指U 月齡或12月齡以下的孩子。如本文中所用術語「早產兒」 ，指在36週妊娠期之前出生之嬰兒。如本文中所用術;吾 足月兒」係指在36週枉娠期時或36週姓娠期後出生之嬰 兒。 除非另有說明，否則如本文中所用術語「新生兒」係指 年齡小於約3個月之嬰兒，包括年齡為零至約2週之嬰兒。 新生兒可為足月兒或早產兒。 除非另有說明，否則如本文中所用術語「嬰兒配方」係 指適於由嬰兒食用之液體及固體營養產品。除非本文中另 有說明，否則術語「嬰兒配方」意欲涵蓋足月兒配方及早 產兒配方。 除非另有說明’否則如本文中所用術語「早產兒配方」 係指適於由早產兒食用之液體及固體營養產品。 如本文中所用術語「微量營養素」係指生物體所需之少 量必要物質。非限制性實例包括維生素、礦物質及其類似 物。 如本文中所用術語「全熱量嬰兒配方」係指其中配方之 熱量密度或能量含量與嬰兒配方中習知包括之熱量密度或 能量含量相比未減少之嬰兒配方。通常，全熱量嬰兒配方 161200.doc 201233333 之能量含量將為至少60〇 kcal/L，或甚至至少660 kca丨/L， 且更通常為至少676 kcal/L，包括600 kcal/L至800 kcal/L。 如本文中所用術語「低熱量嬰兒配方」係指以單位體積 計之能量含量低於全熱量嬰兒配方之嬰兒配方。 當參考嬰兒配方之微量營養素含量時，術語「高微量營 養素」或「高微量營養素含量」意謂嬰兒配方中至少8〇0/〇 微量營養素以與嬰兒配方中習知包括之微量營養素量幾乎 相同之量（對於大部分微量營養素，通常在約82%内）存 在0 除非另有說明，否則如本文中所用之所有百分 及比率均以組合物總重量計。除非另有說明，否則所有該 等重里（當其係關於所列舉成分時）均基於活性物含量且因 此不包括市售物質中可能包括之溶劑或副產物。 無論是否特定揭示’如本文中所用之數值範圍均意欲包 括該範圍内之每—數值及數值子集。此外，該等數值範圍 應視為對針㈣範_料數值或數值+ #之纟張提供支 持。舉例而言’說明H0應視為支持2至8、3至7、K 6、1至9、3.6至4·ό、3·5至9·9等之範圍。 有有說明或與產生參考之上下文明顯矛盾’否則所 =本發明之單數特徵或限制之參考均應包括相應複 徵或限制，且反之亦然。 ， 除非另有說明或與產生參考組合之上下文 則可以任何次序進行如本文中所用之方法或過程步二： 161200.doc 201233333 有組合。 本發明之嬰兒配方之多種實施例亦可實質上不含任何本 文中所播述之視情況選用或所選成分或特徵，限制條件為 其餘嬰兒配方仍含有本文_所描述之所有所需成分或特 徵。在此情形下且除非另有說明，否則術語「實質上不 含」意謂所選嬰兒配方含有小於功能性量之視情況選用之 成分，通常為小於1重量％(包括小於〇·5重量％，包括小於 〇. 1重量％且亦包括0重量％)該視情況選用或所選成分。 本發明之嬰兒配方及方法可包含本文中所描述之產品及 方法之要素以及本文中所描述或以其他方式適用於營養嬰 兒配方應用之任何其他或視情況選用之要素、由本文中所 描述之產品及方法之要素以及本文中所描述或以其他方式 適用於營養嬰兒配方應用之任何其他或視情況選用之要素 組成或基本上由本文中所描述之產品及方法之要素以及本 文中所描述或以其他方式適用於營養嬰兒配方應用之任何 其他或視情況選用之要素組成》 產品形式 本發明之嬰兒配方可以任何已知或其他適當口服產品形 式調配及投與。任何固體、半固體、液體、半液體或粉末 形式（包括其組合或變化）均適用於本發明，限制條件為該 等形式可安全及有效經口傳遞亦於本文中定義之必要成分 至個體。 適用於本文中揭示之產品及方法之產品形式之特定非限 制性實例包括例如液體及粉末早產兒配方、液體及粉末足 161200.doc -12- 201233333 月兒配方以及液體及粉末元素及半元素配方。 本發明之嬰兒配方較佳調配為膳食產品形式，其於本文 中定義為包含本發明之必要成分且呈含有脂肪、蛋白質及 碳水化合物令之至少一者之產品形式之實施例。 可用足夠種類及數量營養物調配嬰兒配方以提供唯一、 主要或附加營養源，或提供用於罹患特定疾病或病狀之嬰 兒之特定營養產品或提供目標營養效益。 本發明之嬰兒配方需要經調配以用於新生兒，包括足月 新生兒及早產新生兒。嬰兒配方較佳經調配以用於在出生 後最初數週内飯養新生兒’且更佳用於顧養〇至2週齡之新 生兒。在一個實施例中’嬰兒配方經調配以用於在出生後 頭兩天饒養新生兒。本文中將該配方稱為「第U天配 方」或「第1-2天嬰兒配方」。在其他實施例中，嬰兒配方 經調配以用於在出生後第3-9天期間餵養新生兒。本文中 將該配方稱為「第3_9天配方」或「第3_9天嬰兒配方」。應 理解投與本發明之第1-2天嬰兒配方不限於僅在出生後頭 兩天期間投與’而在一些實施例中亦可投與較大嬰兒。類 似地’投與第3_9天嬰兒配方不限於僅在出生後第3_9天期 間投與’而在一些實施例中亦可投與其他年齡之嬰兒。 營養液體 營養液體包括濃縮營養液體及即食型營養液體。該等營 養液體最通常調配為懸浮液、乳液或澄清或實質上澄清液 體0 適用營養乳液可為包含蛋白質、脂肪及碳水化合物之水 161200.doc -13· 201233333 性乳液。該等乳液通常在約rc至約25t:下為可流動或可 飲用液體且通常呈水包油、油包水或複合物水性乳液形 式但忒等乳液最通常呈具有連續水相及不連續油相之水 包油乳液形式。 呂養液體可為且通常為可穩定儲存。營養液體通常含有 以營養液體重量計至多約95重量％水，約5〇重量％至約％ 重量％，亦包括約60重量〇/❶至約90重量％，且亦包括約7〇 重量。/。至約85重量％水。營養液體可具有多種產品密度， 但其密度最通常大於約丨.03 g/mL，包括大於約丨 g/mL ’包括大於約！ 〇55 g/mL，包括約丨％咖l至約1 η g/mL ,且亦包括約 1.085 g/mL·至約 1.1〇 g/mL。 營養液體之pH值可在約3_5至約8範圍内，但最佳在約 4.5至約7.5範圍内，包括在約55至約73範圍内，包括在約 6.2至約7.2範圍内。 ’但典型食 ，或甚至至 mL至約300 mL至約250 儘管營養液體之食用量可視多種變數而不同 用量通常為至少約2毫升，或甚至至少約5毫升 少約10 mL，或甚至至少約25 mL，包括約2 mL之範圍，包括約1〇〇 mL至約3〇〇 、約4 約10 mL至約240 mL及約190 mL、約 150 mL至約 250 mL· mL 至約 240 mL。 營養粉末 營養粉末呈可流動或實質上可流動顆粒組合物形式，或 至呈顆粒組合物形式。尤其合適營養粉末形式包括喷霧 乾燥、聚結或乾燥摻合粉末組合物或其組合，或由其他合 \sm0.doc 201233333 適方法製備之粉末。組合物可易於用匙子或其他類似裝置 舀取及量測，其中組合物可易於用合適水性液體（通常為 水）復原以形成營養液體（諸如嬰兒配方）以用於即刻經口或 經腸使用。在此情形下，「即刻」使用通常意謂在復原後 約48小時内使用，最通常在約24小時内使用，較佳在復原 後立即使用或在復原後20分鐘内使用。 能量含量 本發明之嬰兒配方與習知足月及早產兒配方相比具有低 能量含量（在本文中可與術語「熱量密度」互換使用）。明 確言之，本發明之嬰兒配方提供約200 kcal/L至小於600 kcal/L(包括約200 kcal/L至約500 kcal/L，且更特定言之約 250 kcal/L至約500 kcal/L)之熱量密度或能量含量。本發明 之第1-2天嬰兒配方提供約200 kcal/L至約360 kcal/L(包括 約 200 kcal/L至約 350 kcal/L，亦包括約 250 kcal/L至約 350 kcal/L、約25 0 kcal/L至約310 kcal/L，且更特定言之約250 kcal/L或約270 kcal/L)之熱量密度或能量含量。本發明之 第3-9天嬰兒配方提供約360 kcal/L至小於600 kcal/L(包括 約370 kcal/L至小於600 kcal/L，亦包括約360 kcal/L至約 500 kcal/L、約 390 kcal/L至約 470 kcal/L，且更特定言之 約406 kcal/L或約410 kcal/L)之熱量密度或能量含量。與本 發明之嬰兒配方相比，習知足月及早產兒配方（本文中亦 稱為「全熱量嬰兒配方」）之熱量密度或能量含量顯著較 高，通常在600 kcal/L至880 kcal/L範圍内。 當本發明之嬰兒配方呈粉末形式時，則意欲在使用前對 161200.doc •15- 201233333 粉末進行復原以獲得上述熱量密度及本文中所描述之其他 營養需求量。同樣地，當本發明之嬰兒配方呈濃縮液體形 式時，則意欲在使用之前稀釋濃縮物以獲得所需熱量密度 及營養需求量。嬰兒配方亦可調配為已具有所需熱量密度 及營養需求量之即食型液體。 本發明之嬰兒配方需要根據本文中詳細描述之方法投與 嬰兒’且詳言之新生兒。該等方法可包括根據本文中所描 述之每日配方攝取量餵食嬰兒配方。 嬰兒配方之能量組分最通常由脂肪、蛋白質及碳水化合 物營養物之組合提供。蛋白質可包含約4%至約4〇%總熱 量，包括約10%以約30%，亦包括約15%至約25% ;碳水化 合物可包含小於40%總熱量，包括約5%至約37%，亦包括 小於約36。/。’且亦包括約20%至約33% ;且脂肪可包含其 餘配方熱量，最通常小於約60%熱量，包括約3〇%至約 60%。其他例示性量闡述於下文中。 微量營養素 在一些實施例中，除低能量含量外，本發明之嬰兒配方 亦由低微量營養素含量（以單位體積計）表徵。 如本文中所描述’先前對調配具有低能量含量之嬰兒配 方之嘗試涉及降低一或多種常量營養素(例如蛋白f '脂 肪、碳水化合物)之含量同時保持微量營養素含量與可見 :全熱量嬰兒配方中之含量近似(以單位體積計”舉例而 。’與1公升全熱量配方相比，i公升該低熱量配方中之一 或多種常量營養素量降低’但其微量營養素量與可見於ι 161200.doc •16· 201233333 公升全熱量配方中者大致相同（對於大部分微量營養素， 通常在至少約82%内然而，常量營養素減少與高微量營 養素之組合可產生具有弱物理屬性之配方。舉例而言，該 等配方通常顏色較深，沈降問題增加且與全熱量配方相比 在產品存放期期間更易於分離。 現意外發現若低熱量配方中之微量營養素量以每千卡 (kcal)計而非以單位體積計而大體上可符合全熱量配方中 者時’則可調配具有改良之物理屬性之低熱量液體嬰兒配 方。舉例而言，100 kcal低熱量配方將包含與可見於1〇〇 kcal全熱量配方中者大致相同量（對於大部分微量營養素， 通常在約80°/。内）之微量營養素。在此實例中，將以ι〇〇 kcal計調配低熱量配方之微量營養素含量。以每kcal計調 配之低熱量液體嬰兒配方具有降低（亦即「低」）之微量營 養素含量（以單位體積計，亦即與相同體積全熱量配方相 比）’且配方之物理外觀呈現整體改良，包括顏色較淺及 穩定性改良。 因此，在一些實施例中，本發明係關於低熱量、低微量 營養素嬰兒配方。如本文中所用，當提及嬰兒配方時，術 語「低微量營養素」或「低微量營養素含量」意謂嬰兒配 方中所包括之至少一部分微量營養素量低於嬰兒配方中習 知包括之相應微量營養素量（以單位體積計應理解，嬰 兒配方中所包括之所有微量營養素之量不一定均需低於習 知相應微量營養素量（以單位體積計）即可達成嬰兒配方視 為低微量營養素嬰兒配方之目的。與習知以單位體積計之 161200.doc 17 201233333 量相比減少嬰兒配方中一部分微量營養素即足夠。 「嬰兒配方中習知包括之」微量營養素量或「習知量」 微量營養素係指業界認可之嬰兒配方中包含之用於實現嬰 兒之適當生長及發育所需之標準微量營養素量（以單位體 積計）。可包括於嬰兒配方中之習知所選微量營養素量（以 單位體積計）闡述於以下表A(即食型配方）及表B(復原粉末 配方）中。 表A :即食型配方 微量營養素 最小量 (每公升） 最大量 (每公升） 殺菌釜滅菌 配方之典型 量(每公升） 無菌滅菌配 方之典型量 (每公升） 維生素A(IU) 2030 4400 3110 3890 維生素D(IU) 406 642 526 506 維生素E(IU) 10.2 15.0 13.3 11.8 維生素Κ(μ8) 54.1 410 125 106 維生素Β1 (μβ) 676 4060 1220 1420 維生素Β2 (Riboflavin) (μκ) 1010 4000 2500 2590 維生素Β6 (pg) 406 556 476 495 維生素B12&g) 1.69 14.0 4.7 5.4 菸酸⑽） 7100 21000 9730 9680 葉酸(gg) 101 600 193 212 泛酸&g) 3040 14400 6220 6710 生物素(pg) 29.7 169 56.1 67.2 維生素C (mg) 60.8 800 416 352 膽驗(mg) 109 203 127 120 肌醇(mg) 31.8 130 39.8 39.9 鈣(mg) 528 620 585 581 磷(mg) 284 398 349 341 鎂(mg) 40.6 71.5 55.7 55.0 161200.doc •18· 201233333 微量營養素 最小量 (每公升） 最大量 (每公升） 殺菌釜滅菌 配方之典型 量(每公升） 無菌滅菌配 方之典型量 (每公升） 鐵(mg) 12.2 15.6 13.4 13.7 .鋅(mg) 5.07 14.0 6.46 6.67 锰㈣ 33.8 235 84.4 87.8 銅㈣ 609 1484 676 728 碘㈣ 40.2 474 118 140 鈉(mg) 163 245 190 189 鉀(mg) 710 1196 946 942 氣化物(mg) 440 551 474 504 氟化物(pg) ·· ... 168 143 硒(Rg) 12.3 36.1 24.9 24.3 表B :復原粉末配方 微量營養素 最小量(每公升） 最大量(每公升） 典型量(每公升） 維生素A(IU) 2030 4820 3583 維生素D(IU) 406 642 563 維生素E(IU) 10.1 15.0 12.6 維生素Κ(μ8) 54.1 410 137 維生素B1 ^g) 676 4060 1560 維生素B2 &g) 1010 4000 1500 維生素B6 &g) 406 556 467 維生素Β12(μ§) 1.69 14.0 5.85 於酸(pg) 7100 21000 9400 葉酸(Rg) 101 600 209 泛酸㈣） 3040 14400 6750 生物素(pg) 29.7 169 63.8 維生素C (mg) 60.8 670 170 膽驗(mg) 108 203 123 肌醇(mg) 31.8 130 41.0 鈣(mg) 536 637 580 磷(mg) 289 408 332 鎂(mg) 40.6 73.3 53.7 161200.doc -19- 201233333 微量營養素 最小量(每公升） 最大量(每公升） 典型量(每公升） 鐵(mg) 12.4 16.1 13.9. 鋅(mg) 5.15 14.4 6.69 猛㈣ 34.3 148 89.7 銅㈣ 618 1519 720 碘㈣ 41.0 489 126 鈉(mg) 165 251 201 鉀(mg) 721 1235 1039 氯化物(mg) 446 565 486 氟化物(pg) ·_— — 116 硒㈣ 12.4 37.0 25.6 可包括於習知嬰兒配方中之例示性非限制性微量營養素 包括維生素A、維生素D、維生素E、維生素K、維生素 B1、維生素B2、維生素B6、維生素B12、菸酸、葉酸、泛 酸、生物素、維生素C、膽鹼、肌醇、鈣、磷、鎂、鐵、 鋅、猛、銅、磁、納、卸、氣化物、氟化物、砸及其組 合。一些例示性習知嬰兒配方可包括銅、填、鐵、弼及鋅 之組合。一些其他例示性習知嬰兒配方可包括銅、鐵及磷 之組合。 在一個特定實施例中，銅、填、鐵、弼及辞中之至少兩 者以比以上表A及B中闡述之量小約5%、或甚至小約 10%，或甚至小約20%，或甚至小約30%，或甚至小約 50%，或甚至小約75%，或甚至小約80%，或甚至小約90% 的量存在於低微量營養素配方中。在另一特定實施例中， 鐵及銅以比以上表A及B中闡述之量小約5%、或甚至小約 10%，或甚至小約20%，或甚至小約30%，或甚至小約 50%，或甚至小約75%，或甚至小約80%，或甚至小約90% 161200.doc -20- 201233333 的量存在於低微量營養素配方中β 應理解’表Α及Β不含本發明之嬰兒配方中可包括之合 適微量營養素之完全清單。此外，本發明之低微量營養素 嬰兒配方無需包含表A&B中列舉之每一微量營養素。本 發明涵蓋包含表A及B中列舉之微量營養素及/或此項技術 中已知適於包含於嬰兒配方中之其他微量營養素中之一或 多者之任何組合的嬰兒配方。可容易地參考歐洲及/或美 國嬰兒配方規則及標準確定該等及其他微量營養素之標準 或習知含量（以每100 kcal計）。 當判定嬰兒配方中之微量營養素含量（以單位體積計）與 習知含量相比是否較低時’應比較「相應微量營養素」之 量。在此情況下，「相應微量營養素」係指所評估之嬰兒 配方中存在之相同微量營養素。舉例而言，若嬰兒配方包 含微量營養素鈣、磷及鎂，則應分別比較嬰兒配方中該等 微量營養素之量與嬰兒配方中習知包括之約、鱗及鎂之量 以判定嬰兒配方中該等微量營養素之量是否較「低」。 本發明之低微量營養素嬰兒配方中所包括之微量營養素 量可表示為以單位體積計之習知相應微量營養素量百分 比。舉例而言，在本發明之一些實施例中，提供低微量營 養素嬰兒配方，其中微量營養素以習知相應微量營養素量 之約30%至約80%之量包括於嬰兒配方中（以單位體積 °十）包括習知相應微量營養素量之約30%至約65%、約 55%至約80%、約4〇%至約7〇%、約4〇%至約5〇%及約6〇% 至約70 /。（均以單位體積計）。通常，本發明之低微量營養 161200.doc •21 · 201233333 素嬰兒配方中至少65%微量營養素，包括至少75%、至少 80%、至少90°/。及100%微量營養素以習知相應微量營養素 量之約30%至約80%之量包括於嬰兒配方中（以單位體積 計）。 在一些實施例中’提供低微量營養素嬰兒配方，其中微 量營養素以習知相應微量營養素量之約30%至約65%之量 包括於嬰兒配方中（以單位體積計），包括習知相應微量營 養素量之約35°/。至約60%、約40%至約50%、約40%至約 45。/。且尤其約40°/。（均以單位體積計）。在該等實施例中， 低微量營養素嬰兒配方中通常至少45%微量營養素，包括 至少50%、至少60°/❶、至少75。/〇、至少80%、至少90%及 100%微量營養素以習知相應微量營養素量之約35%至約 6〇0/。之量包括於嬰兒配方中（以單位體積計在其他實施 例中’低微量營養素嬰兒配方中至少丨〇%微量營養素，包 括至少25%、至少50%、至少6〇%、至少75%及至少8〇%微 量營養素以習知相應微量營養素量之約4〇%至約5 〇%之量 包括於嬰兒配方中（以單位體積計該等低微量營養素嬰 兒配方可包括例如第1_2天嬰兒配方。 在其他實施例中’提供低微量營養素嬰兒配方，其中微 量呂養素以習知相應微量營養素量之約55%至約80%之量 匕括於嬰兒配方中（以單位體積計），包括習知相應微量營 養素量之約6〇%至約75%、約6〇%至約7〇%、約至約 65%且尤其約6〇%(均以單位體積計p在該等實施例中， 低微量營養素嬰兒配方中通常至少30°/。微量營養素，包括 161200.doc -22· 201233333 至夕50/。、至少6〇%、至少75%、至少、至少及 100%微量營養素以習知相應微量營養素量之約55%至約 8〇%之量包括於嬰兒配方中(以單位體積計）。在其他實施 例中’低微量營養素嬰兒配方中至少1()%微量營養素，包 括至/ 25%、至少5G%、至少6()%、至少75%及至少微 量營養素以習知相應微量營養素量之約60%至約70%之量 包括於嬰兒配方中（以單位體積計）。該等低微量營養素嬰 兒配方可包括例如第3-9天嬰兒配方。 在其中微量營養素包括礦物質之一些實施例中，礦物質 以習知相應礦物質的量之約3G%至約祕之量包括於低微 量營養素嬰兒配方中（以單位體積計），包括f知相應礦物 質的量之約30%至約65%、約55%至約8〇%、約4〇%至約 70%、約40%至約50%及約6〇%至約7〇%(均以單位體積 计）通常，本發明之低微量營養素嬰兒配方中至少丨〇% , 包括至少45%、至少50% '至少6〇%、至少7〇%、至少 75%、至少8G%、至少9Q%及⑽％礦物f以習知相應礦物 質的量之約30%至約80%之量包括於嬰兒配方中（以單位體 積計）。 在其他實施例中，礦物質以習知相應礦物質的量之約 30。/。至約65%之量包括於低微量營#素嬰絲方巾（以單位 體積計），包括習知相應礦物質的量之約35%至約6〇%、約 40〇/。至約50%、約40%至約45%且尤其約4〇%(均以單位體積 計）》在該等實施例中，低微量營養素嬰兒配方中通常至 少1〇%礦物質，包括至少25。/。、至少5〇%、至少6〇%、至少 161200.doc -23· 201233333 75%、至少80%、至少90%及100%礦物質以習知相應礦物 質的量之約30%至約65°/。之量包括於嬰兒配方中（以單位體 積計）。在其他實施例中，低微量營養素嬰兒配方中至少 10%，包括至少25°/。、至少50%、至少60%、至少75%、至 少80%、至少90%及100%礦物質以習知相應礦物質的量之 約40%至約50°/。之量包括於嬰兒配方中（以單位體積計）。 該等低微量營養素嬰兒配方可包括例如第1 ·2天嬰兒配 方。 在其他實施例中’礦物質以習知相應礦物質的量之約 55%至約80 %之量包括於低微量營養素嬰兒配方中（以單位 體積計）’包括習知相應礦物質的量之約60%至約75%、約 60%至約70%、約60%至約65°/◦且尤其約6〇%(均以單位體積 計）。在該等實施例中，低微量營養素嬰兒配方中通常至 少10/0’包括至少25%、至少50%、至少60%、至少75%、 至少80。/。、至少90%及100%礦物質以習知相應礦物質的量 之約55°/。至約80¾之量包括於嬰兒配方中（以單位體積 «十）。在其他貫施例中，低微量營養素嬰兒配方中至少 10%，包括至少25%、至少50。/。、至少6〇%、至少75%、至 少80%、至少90%及100%礦物質以習知相應礦物質的量之 約6 0 %至約7 〇 %之量包括於嬰兒配方中（以單位體積計）。 s亥等低微量營養素嬰兒配方可包括例如第3_9天嬰兒配 方。 在其中微量營養素包括維生素之一些實施例中，維生素 以習知相應維生素量之約30%至約8〇%之量包括於低微量 161200.doc -24- 201233333 營養素嬰兒配方中（以單位體積計）’包括習知相應維生素 量之約30°/。至約65°/。、約55%至約80%、約40%至約70%、 約40%至約50%及約60%至約70%(均以單位體積計）。通 常，本發明之低微量營養素嬰兒配方中至少45%，包括至 少50%、至少60%、至少70%、至少8〇%、至少85%、至少 90°/。及1〇〇。/。維生素以習知相應維生素量之約3〇%至約8〇0/〇 之量包括於嬰兒配方中（以單位體積計）。 耷其他實施例中，維生素以習知相應維生素量之約3〇0/〇 至約6 5 %之量包括於低微量營養素嬰兒配方中（以單位體積 计）’包括習知相應維生素量之約3 5%至約60%、約40%至 約50°/。、約40%至約45%且尤其約40%(均以單位體積計）。 在該等實施例中，低微量營養素嬰兒配方中通常至少1〇% 維生素’包括至少25%、至少50%、至少60%、至少75%、 至少80°/。、至少90%及100°/。維生素以習知相應維生素量之 約30%至約65%之量包括於嬰兒配方中（以單位體積計）。 在其他實施例中，低微量營養素嬰兒配方中至少〗〇%維生 素，包括至少25%、至少50%、至少60%、至少75%及至少 80%維生素以習知相應維生素量之約4〇%至約5〇%之量包 括於嬰兒配方中（以單位體積計）。該等低微量營養素嬰兒 配方可包括例如第1 _2天嬰兒配方。 在其他實施例中，維生素以習知相應維生素量之約55〇/〇 至約80%之量包括於低微量營養素嬰兒配方中（以單位體積 计）’包括習知相應維生素量之約6〇%至約75%、約6〇〇/〇至 約70%、約60%至約65%且尤其約6〇%(均以單位體積計p 161200.doc -25- 201233333 在該等實施例中，低微量營養素嬰兒配方中通常至少 10% ’包括至少25%、至少50%、至少60%、至少75%、至 少80%、至少90%及100%維生素以習知相應維生素量之約 55%至約80%之量包括於嬰兒配方中（以單位體積計在 其他實施例中’低微量營養素嬰兒配方中至少1 〇%，包括 至少25°/。、至少50%、至少60%、至少75%、至少80%及至 少90°/。維生素以習知相應維生素量之約6〇%至約7〇%之量 包括於嬰兒配方中（以單位體積計）。該等低微量營養素嬰 兒配方可包括例如第3-9天嬰兒配方。 可包含於本發明之嬰兒配方中之合適微量營養素包括維 生素或相關營養物、礦物質及其組合。合適維生素之非限 制性實例包括維生素A、維生素D、維生素e、維生素κ、 維生素B1、維生素B2、吡哆醇、維生素B5、維生素B6、 維生素B12、菸酸、葉酸、泛酸、生物素、維生素c、膽 驗、肌醇、抗壞血酸、其鹽及衍生物以及其組合。 可包括於本發明之嬰兒配方中之合適礦物質之非限制性 實例包括鈣、磷、鎂、鐵、鋅、錳、鋼、碘、納、钟、 翻、鉻、氯化物、氟化物、ί西及其組合。 任何嬰兒配方均可經調配具有本文中揭示之低微量營養 素含量’包括殺菌爸滅菌及無菌滅菌即食型營養液體、濃 縮營養液體及營養粉末。 常量營養素 除本文中所描述之微量營養素外’本發明之嬰兒配方亦 可包含一或多種常量營養素。常量營養素包括蛋白質、脂 161200.doc • 26· 201233333 肪、碳水化合物及其組合。適用於本文中之常量營養素包 括任何已知或以其他方式適用於口服營養產品中之蛋白 質、脂肪、碳水化合物或其來源，限制條件為常量營養素 可安全且有效經口投與嬰兒且以其他方式與嬰兒配方中其 他成分相容。 儘管蛋白質、月曰肪及奴水化合物之總濃度或量可視產品 形式（例如粉末或即食型液體）及所欲使用者之目標腾食需 要不同’但該等濃度或里通常屬於下表中描述之具體範圍 中之一者内（各數值前均加上術語「約」），包括本文中所 描述之任何其他必需脂肪、蛋白質及/或碳水化合物成 分。對於粉末實施例，下表中之含量為粉末復原後之含 量。 表c 營養物(g/100 mL) 實例A 實例B 0.6 至 0.9 蛋白質 0.55.1.0 脂肪 1.25.2.5 1.4 至 2.3 碳水化合物 2.75.6.5 3.1 至 6.1 蛋白質、知肪及被水化合物之總濃度或量亦可視嬰兒配 方是為第1-2天配方還是為第3-9天配方而不同。第1_2天配 方及第3-9天配方中蛋白質、脂肪及碳水化合物之濃度最 通常經調配屬於下表中描述之具體範圍中之任一者内（各 數值前均加上術語「約」），包括本文中所描述之任何其 他必需脂肪、蛋白質及/或碳水化合物成分。對於粉末實 施例’下表中之含量為復原後之含量。 161200.doc •27- 201233333Unless otherwise stated, the term "infant" as used herein refers to a child who is U months old or under 12 months of age. The term "preterm infant" as used herein refers to an infant born before the 36-week gestation period. As used herein, "sufficient month" refers to an infant born after 36 weeks of gestation or after 36 weeks of gestation. The term "neonatal" as used herein, unless otherwise indicated, refers to an infant who is younger than about 3 months, including infants from zero to about two weeks old. Newborns can be term infants or premature babies. The term "infant formula" as used herein, unless otherwise indicated, refers to liquid and solid nutritional products suitable for consumption by infants. Unless otherwise stated herein, the term "infant formula" is intended to cover both full term formula and preterm formula. Unless otherwise stated, the term "preterm formula" as used herein refers to liquid and solid nutritional products suitable for consumption by premature infants. The term "micronutrient" as used herein refers to a small amount of essential material required by an organism. Non-limiting examples include vitamins, minerals, and the like. The term "full calorie infant formula" as used herein refers to an infant formula in which the caloric density or energy content of the formulation is not reduced compared to the heat density or energy content conventionally included in infant formulas. Typically, the full calorie infant formula 161200.doc 201233333 will have an energy content of at least 60〇kcal/L, or even at least 660 kca丨/L, and more typically at least 676 kcal/L, including 600 kcal/L to 800 kcal/ L. The term "low calorie infant formula" as used herein refers to an infant formula that has a lower energy content per unit volume than a full calorie infant formula. When referring to the micronutrient content of an infant formula, the term "high micronutrient" or "high micronutrient content" means at least 8 〇 0 / 〇 micronutrients in the infant formula to be almost the same as the amount of micronutrients conventionally included in infant formula. The amount (usually within about 82% for most micronutrients) is present. Unless otherwise indicated, all percentages and ratios as used herein are based on the total weight of the composition. All such weights, when referring to the recited ingredients, are based on the active level and therefore do not include solvents or by-products that may be included in the commercially available materials, unless otherwise stated. Whether or not a particular disclosure is used as used herein is intended to include a range of values and a subset of the values. In addition, these numerical ranges should be considered as support for the needle (four) model value or value + #纟. For example, 'H0' should be considered to support the range of 2 to 8, 3 to 7, K 6, 1 to 9, 3.6 to 4, 3, 3.5 to 9. 9 and the like. There is a description or a conflict with the context in which the reference is made. Otherwise, references to the singular features or limitations of the present invention should include the corresponding singular or limitation, and vice versa. Unless otherwise stated or in combination with the context in which the reference is made, the method or process as used herein may be performed in any order. Step 2: 161200.doc 201233333 There are combinations. The various embodiments of the infant formula of the present invention may also be substantially free of any optional ingredients or features selected as described herein, with the proviso that the remaining infant formula still contains all of the desired ingredients described herein or feature. In this case and unless otherwise stated, the term "substantially free" means that the selected infant formula contains less than 1% by weight (including less than 〇 5% by weight) of the optional ingredients, which are less than the functional amount. , including less than 0.1% by weight and also including 0% by weight, depending on the selected or selected ingredients. The infant formula and method of the present invention may comprise the elements of the products and methods described herein as well as any other or optionally selected elements described herein or otherwise suitable for use in a nutritional infant formula application, as described herein. The elements of the products and methods, as well as any other or optional elements described herein or otherwise suitable for use in a nutritional infant formula application, consist essentially of or consist essentially of the elements of the products and methods described herein and or described herein or Any other or optional elemental composition that is otherwise suitable for use in nutritional infant formula applications. Product Form The infant formula of the present invention can be formulated and administered in any known or other suitable oral product form. Any solid, semi-solid, liquid, semi-liquid or powder form, including combinations or variations thereof, is suitable for use in the present invention, provided that such forms are safe and effective for oral delivery of the essential ingredients as defined herein to the individual. Specific non-limiting examples of product forms suitable for use in the products and methods disclosed herein include, for example, liquid and powder preterm formulas, liquid and powdered feet, 161200.doc -12-201233333, and liquid and powder elements and semi-element formulas. . The infant formula of the present invention is preferably formulated in the form of a dietary product, which is defined herein as an embodiment comprising the essential ingredients of the present invention and in the form of a product comprising at least one of a fat, a protein and a carbohydrate. Infant formula can be formulated with sufficient types and amounts of nutrients to provide a unique, primary or additional source of nutrients, or to provide specific nutritional products for infants suffering from a particular disease or condition or to provide targeted nutritional benefits. The infant formula of the present invention needs to be formulated for use in newborns, including term newborns and premature newborns. Infant formulas are preferably formulated for use in raising newborns during the first few weeks of life and are better for newborns up to 2 weeks of age. In one embodiment, the infant formula is formulated for feeding the newborn in the first two days after birth. This formula is referred to herein as "U Day Formulation" or "Day 1-2 Infant Formulation". In other embodiments, the infant formula is formulated for feeding the newborn during the 3-9th day after birth. This formula is referred to herein as "3rd-9th Formula" or "3rd-9th Infant Formula". It is to be understood that the infant formula formulated on Days 1-2 of the present invention is not limited to being administered only during the first two days after birth. In some embodiments, larger infants may also be administered. Similarly, the administration of the 3rd-9th infant formula is not limited to being administered only during the 3rd-9th day after birth. In some embodiments, infants of other ages may also be administered. Nutrient Liquids Nutrient liquids include concentrated nutrient liquids and ready-to-eat nutrient liquids. These nutrient liquids are most often formulated as suspensions, emulsions or as clear or substantially clear liquids. 0 Suitable nutritional emulsions can be water containing proteins, fats and carbohydrates 161200.doc -13· 201233333 Sexual emulsion. The emulsions are typically in the form of a flowable or potable liquid at about rc to about 25 t: and are typically in the form of an oil-in-water, water-in-oil or complex aqueous emulsion. The emulsions such as hydrazine are most often in the form of continuous aqueous and discontinuous oils. In the form of an oil-in-water emulsion. The Lvyang liquid can be and is usually stable for storage. The nutritional liquid typically contains up to about 95% by weight water, from about 5% by weight to about % by weight, based on the weight of the nutritional liquid, also including from about 60 weights 〇/❶ to about 90% by weight, and also includes about 7 重量 by weight. /. Up to about 85% by weight water. The nutritional liquid can have a variety of product densities, but its density is most typically greater than about 丨.03 g/mL, including greater than about 丨 g/mL 'including greater than about! 〇 55 g/mL, including from about 1% to about 1 η g/mL, and also including from about 1.085 g/mL· to about 1.1 〇 g/mL. The pH of the nutritional liquid may range from about 3 to about 5, but is preferably in the range of from about 4.5 to about 7.5, including from about 55 to about 73, including from about 6.2 to about 7.2. 'Although typical foods, or even up to about 300 mL to about 250, although the amount of nutrient liquid consumed can vary from at least about 2 ml, or even at least about 5 ml, to about 10 mL, or even at least about 25 mL, including a range of about 2 mL, includes from about 1 mL to about 3 Torr, from about 4 to about 10 mL to about 240 mL, and from about 190 mL, from about 150 mL to about 250 mL·mL to about 240 mL. Nutritional Powder The nutritional powder is in the form of a flowable or substantially flowable particulate composition, or in the form of a particulate composition. Particularly suitable nutritional powder forms include spray-dried, coalesced or dry-blended powder compositions or combinations thereof, or powders prepared by other suitable methods of sm.doc 201233333. The composition can be easily taken and measured with a spoon or other similar device, wherein the composition can be easily reconstituted with a suitable aqueous liquid (usually water) to form a nutritional liquid (such as an infant formula) for immediate oral or enteral use. . In this case, "immediate" use generally means use within about 48 hours of recovery, most typically within about 24 hours, preferably immediately after recovery or within 20 minutes of recovery. Energy Content The infant formula of the present invention has a low energy content compared to conventional full-term and preterm formulas (as used herein interchangeably with the term "caloric density"). In particular, the infant formula of the present invention provides from about 200 kcal/L to less than 600 kcal/L (including from about 200 kcal/L to about 500 kcal/L, and more specifically from about 250 kcal/L to about 500 kcal/ L) The heat density or energy content. The infant formula of Days 1-2 of the present invention provides from about 200 kcal/L to about 360 kcal/L (including from about 200 kcal/L to about 350 kcal/L, also including from about 250 kcal/L to about 350 kcal/L, A heat density or energy content of from about 25 kcal/L to about 310 kcal/L, and more specifically about 250 kcal/L or about 270 kcal/L. The 3-9 day infant formula of the present invention provides from about 360 kcal/L to less than 600 kcal/L (including from about 370 kcal/L to less than 600 kcal/L, also including from about 360 kcal/L to about 500 kcal/L, A heat density or energy content of from about 390 kcal/L to about 470 kcal/L, and more specifically about 406 kcal/L or about 410 kcal/L. Compared to the infant formula of the present invention, the conventional full-term and preterm formula (also referred to herein as "full calorie infant formula") has a significantly higher caloric density or energy content, typically in the range of 600 kcal/L to 880 kcal/L. Inside. When the infant formula of the present invention is in powder form, it is intended to recover the 161200.doc •15-201233333 powder prior to use to achieve the above caloric density and other nutritional requirements as described herein. Similarly, when the infant formula of the present invention is in the form of a concentrated liquid, it is intended to dilute the concentrate prior to use to achieve the desired caloric density and nutritional requirements. Infant formulas can also be formulated as ready-to-feed liquids that have the required caloric density and nutritional requirements. The infant formula of the present invention requires the administration of a baby' and a detailed newborn according to the methods described in detail herein. The methods can include feeding the infant formula according to the daily formula intake described herein. The energy component of an infant formula is most often provided by a combination of fat, protein and carbohydrate nutrients. The protein may comprise from about 4% to about 4% total calories, including about 10% to about 30%, and also about 15% to about 25%; the carbohydrate may comprise less than 40% total calories, including from about 5% to about 37% %, also includes less than about 36. /. And also includes from about 20% to about 33%; and the fat may comprise the remainder of the formula, most typically less than about 60%, including from about 3% to about 60%. Other illustrative amounts are set forth below. Micronutrients In some embodiments, in addition to low energy content, the infant formula of the present invention is also characterized by a low micronutrient content (in terms of unit volume). As previously described, 'previous attempts to formulate infant formulas with low energy content involve reducing the content of one or more macronutrients (eg, protein f 'fat, carbohydrate) while maintaining micronutrient content and visible: in a full calorie infant formula The content is approximated (in terms of unit volume). 'Compared to 1 liter of full-calorie formula, i liters of this low-calorie formula reduces the amount of one or more macronutrients', but its micronutrient content can be seen in ι 161200.doc • 16· 201233333 liters of all-calorie formula are roughly the same (for most micronutrients, usually at least about 82%, however, the combination of macronutrient reduction and high micronutrients can produce formulations with weak physical properties. For example, These formulations are usually darker in color, have increased settling problems and are easier to separate during the product shelf life than the full calorie formula. It has been surprisingly found that if the amount of micronutrients in a low calorie formula is in kilocalories instead of When the unit volume is used to substantially conform to the total heat formula, then the modified physical genus can be adjusted. Low calorie liquid infant formula. For example, a 100 kcal low calorie formula will contain approximately the same amount as found in a 1 kcal full calorie formula (for most micronutrients, typically within about 80°/.) Micronutrients. In this example, the micronutrient content of the low calorie formula will be formulated in ι〇〇kcal. The low calorie liquid infant formula formulated per kcal has a reduced (ie, "low") micronutrient content (in terms of The unit volume, that is, compared to the same volume of the full heat formula) and the physical appearance of the formulation presents an overall improvement, including lighter color and improved stability. Thus, in some embodiments, the present invention relates to low heat, low Micronutrient Infant Formulation As used herein, the term "low micronutrient" or "low micronutrient content" when referring to an infant formula means that at least a portion of the micronutrient content included in the infant formula is lower than in infant formula. The amount of corresponding micronutrients included (in terms of unit volume, all micronutrients included in the infant formula are understood The amount may not necessarily be lower than the conventional micronutrient amount (in terms of unit volume) to achieve the purpose of the infant formula as a low micronutrient infant formula. It is known to be 161200.doc 17 201233333 by unit volume. It is sufficient to reduce a portion of the micronutrients in the infant formula. “The amount of micronutrients or “negative amounts” that are commonly included in infant formulas. Micronutrient refers to the appropriate growth and development of infants included in the industry-approved infant formula. The amount of standard micronutrients required (in terms of unit volume). The amount of micronutrients selected in the infant formula (in terms of unit volume) is described in Table A below (ie, diet formulation) and Table B (reconstituted powder). In the formula) Table A: Instant formula Minimal nutrient minimum (per liter) Maximum amount (per liter) Typical amount of sterilization kit (per liter) Typical amount of sterile sterilization formula (per liter) Vitamin A (IU) 2030 4400 3110 3890 Vitamin D (IU) 406 642 526 506 Vitamin E (IU) 10.2 15.0 13.3 11.8 Vitamin Κ (μ8) 54.1 410 125 106 Dimensions Prime 1 (μβ) 676 4060 1220 1420 Vitamin Β 2 (Riboflavin) (μκ) 1010 4000 2500 2590 Vitamin Β 6 (pg) 406 556 476 495 Vitamin B12 & g) 1.69 14.0 4.7 5.4 Niacin (10)) 7100 21000 9730 9680 Folic acid (gg 101 600 193 212 Pantothenic acid & g) 3040 14400 6220 6710 Biotin (pg) 29.7 169 56.1 67.2 Vitamin C (mg) 60.8 800 416 352 Biliary test (mg) 109 203 127 120 Inositol (mg) 31.8 130 39.8 39.9 Calcium (mg) 528 620 585 581 Phosphorus (mg) 284 398 349 341 Magnesium (mg) 40.6 71.5 55.7 55.0 161200.doc •18· 201233333 Minimum amount of micronutrients (per liter) Maximum amount (per liter) Sterilization formula Typical amount (per liter) Typical amount of sterile sterile formulation (per liter) Iron (mg) 12.2 15.6 13.4 13.7. Zinc (mg) 5.07 14.0 6.46 6.67 Manganese (4) 33.8 235 84.4 87.8 Copper (4) 609 1484 676 728 Iodine (4) 40.2 474 118 140 Sodium (mg) 163 245 190 189 Potassium (mg) 710 1196 946 942 Vapor (mg) 440 551 474 504 Fluoride (pg) ·· ... 168 143 Selenium (Rg) 12.3 36.1 24.9 24.3 Table B: Recovery Powder formula micronutrient minimum amount (per liter) Large amount (per liter) Typical amount (per liter) Vitamin A (IU) 2030 4820 3583 Vitamin D (IU) 406 642 563 Vitamin E (IU) 10.1 15.0 12.6 Vitamin Κ (μ8) 54.1 410 137 Vitamin B1 ^g) 676 4060 1560 Vitamin B2 &g) 1010 4000 1500 Vitamin B6 &g) 406 556 467 Vitamin Β12 (μ§) 1.69 14.0 5.85 Acid (pg) 7100 21000 9400 Folic acid (Rg) 101 600 209 Pantothenic acid (iv) 3040 14400 6750 Prime (pg) 29.7 169 63.8 Vitamin C (mg) 60.8 670 170 Gallstone (mg) 108 203 123 Inositol (mg) 31.8 130 41.0 Calcium (mg) 536 637 580 Phosphorus (mg) 289 408 332 Magnesium (mg) 40.6 73.3 53.7 161200.doc -19- 201233333 Minimum amount of micronutrients (per liter) Maximum amount (per liter) Typical amount (per liter) Iron (mg) 12.4 16.1 13.9. Zinc (mg) 5.15 14.4 6.69 Meng (4) 34.3 148 89.7 Copper (iv) 618 1519 720 Iodine (iv) 41.0 489 126 Sodium (mg) 165 251 201 Potassium (mg) 721 1235 1039 Chloride (mg) 446 565 486 Fluoride (pg) ·_- — 116 Selenium (4) 12.4 37.0 25.6 May be included Illustrative non-limiting micronutrients in infant formula include vitamin A, Vitamin D, vitamin E, vitamin K, vitamin B1, vitamin B2, vitamin B6, vitamin B12, niacin, folic acid, pantothenic acid, biotin, vitamin C, choline, inositol, calcium, phosphorus, magnesium, iron, zinc , violent, copper, magnetic, nano, unloading, vapor, fluoride, antimony and combinations thereof. Some exemplary conventional infant formulas may include a combination of copper, filler, iron, strontium, and zinc. Some other exemplary conventional infant formulas may include a combination of copper, iron, and phosphorus. In a particular embodiment, at least two of copper, fill, iron, tantalum, and rhetoric are about 5% less, or even about 10% smaller, or even about 20% smaller than the amounts set forth in Tables A and B above. , or even about 30% smaller, or even about 50% smaller, or even about 75% smaller, or even about 80% smaller, or even about 90% smaller in the low micronutrient formulation. In another particular embodiment, the iron and copper are about 5% less, or even about 10% smaller, or even about 20% smaller, or even about 30% smaller, or even less than 30%, or even less than the amounts set forth in Tables A and B above. About 50% smaller, or even about 75% smaller, or even about 80% smaller, or even about 90% smaller. 161200.doc -20- 201233333 The amount is present in low micronutrient formulas. β should be understood. A complete list of suitable micronutrients that may be included in the infant formula of the present invention. In addition, the low micronutrient infant formula of the present invention need not contain each of the micronutrients listed in Tables A & B. The present invention encompasses infant formulas comprising any of the micronutrients listed in Tables A and B and/or any combination of one or more of the other micronutrients known in the art to be included in an infant formula. Standards or known levels of these and other micronutrients (in terms of 100 kcal) can be readily determined by reference to European and/or US infant formula rules and standards. When it is determined whether the micronutrient content (in terms of unit volume) in the infant formula is lower than the conventional content, the amount of the corresponding micronutrient should be compared. In this case, "corresponding micronutrient" means the same micronutrients present in the infant formula being evaluated. For example, if the infant formula contains micronutrients such as calcium, phosphorus, and magnesium, the amount of the micronutrients in the infant formula and the amount of the scale, scale, and magnesium conventionally included in the infant formula should be compared to determine the infant formula. Is the amount of micronutrients less "lower"? The micronutrient amount included in the low micronutrient infant formula of the present invention can be expressed as a percentage of the conventional corresponding micronutrient amount per unit volume. For example, in some embodiments of the invention, a low micronutrient infant formula is provided wherein the micronutrient is included in the infant formula in an amount of from about 30% to about 80% of the amount of the corresponding micronutrient (in unit volume) 10) comprising from about 30% to about 65%, from about 55% to about 80%, from about 4% to about 7%, from about 4% to about 5% and about 6% of the amount of the corresponding micronutrient. To about 70 /. (both in unit volume). Typically, the low micronutrient of the present invention comprises at least 65% micronutrients in the infant formula, including at least 75%, at least 80%, at least 90°/. And 100% micronutrients are included in the infant formula (in unit volume) in amounts ranging from about 30% to about 80% of the corresponding micronutrient. In some embodiments, 'providing a low micronutrient infant formula, wherein the micronutrients are included in the infant formula (in unit volume) in an amount from about 30% to about 65% of the amount of the corresponding micronutrient, including conventionally corresponding micronutrients The amount of nutrients is about 35°/. To about 60%, from about 40% to about 50%, from about 40% to about 45. /. And especially about 40°/. (both in unit volume). In such embodiments, the low micronutrient infant formula typically comprises at least 45% micronutrient, including at least 50%, at least 60°/❶, at least 75. / 〇, at least 80%, at least 90% and 100% of the micronutrients are known to be about 35% of the corresponding micronutrient amount to about 6 〇 0 /. The amount is included in the infant formula (in the other embodiments, at least 丨〇% micronutrient in the low micronutrient infant formula, including at least 25%, at least 50%, at least 6%, at least 75%, and at least The 8 5% micronutrient is included in the infant formula in an amount from about 4% to about 5% by weight of the corresponding micronutrient (the low micronutrient infant formula per unit volume may include, for example, the 1st-2 day infant formula. In other embodiments, 'providing a low micronutrient infant formula, wherein the amount of luciferin is included in the infant formula (in unit volume) in an amount from about 55% to about 80% of the amount of the corresponding micronutrient, including conventionally corresponding From about 6% to about 75%, from about 6% to about 7%, from about 6% to about 65%, and especially from about 6% by weight of the micronutrient (both in unit volume, p in the examples, low traces) The nutrient infant formula is usually at least 30°/. Micronutrients, including 161200.doc -22· 201233333 to 50%, at least 6〇%, at least 75%, at least, at least 100% micronutrient, known micronutrients Approximately 55% of the amount to about 8〇 The amount of % is included in the infant formula (in unit volume). In other embodiments, at least 1 (%) micronutrient in the low micronutrient infant formula, including to / 25%, at least 5G%, at least 6 ()% At least 75% and at least the micronutrient is included in the infant formula (in unit volume) in an amount from about 60% to about 70% of the amount of the corresponding micronutrient. The low micronutrient infant formula may include, for example, the third 9-day infant formula. In some embodiments in which the micronutrients include minerals, the minerals are included in the low micronutrient infant formula (in terms of unit volume, from about 3G% to about the amount of the known minerals). And the amount of the corresponding minerals is from about 30% to about 65%, from about 55% to about 8%, from about 4% to about 70%, from about 40% to about 50%, and from about 6% to About 7% by weight (both in unit volume) Typically, at least 丨〇% of the low micronutrient infant formula of the present invention comprises at least 45%, at least 50% 'at least 6%, at least 7%, at least 75%, At least 8 G%, at least 9 Q%, and (10)% of the mineral f is included in an amount of from about 30% to about 80% of the amount of the corresponding mineral. In infant formula (in terms of unit volume). In other embodiments, the mineral is included in the low micro-battalion #素婴丝巾(s) in an amount of about 30% to about 65% of the amount of the corresponding mineral. In terms of unit volume, including from about 35% to about 6%, from about 40% to about 50%, from about 40% to about 45%, and especially about 4% by weight of the corresponding minerals. Unit volume) In these examples, the low micronutrient infant formula typically comprises at least 1% minerals, including at least 25%, at least 5%, at least 6%, at least 161200.doc -23. 201233333 75%, at least 80%, at least 90%, and 100% minerals are from about 30% to about 65°/ of the amount of the corresponding mineral. The amount is included in the infant formula (in terms of unit volume). In other embodiments, at least 10% of the low micronutrient infant formula comprises at least 25°/. At least 50%, at least 60%, at least 75%, at least 80%, at least 90% and 100% of the minerals are from about 40% to about 50% of the amount of the corresponding mineral. The amount is included in the infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, Day 1-2 baby formula. In other embodiments, the amount of minerals included in the low micronutrient infant formula (in terms of unit volume) is from about 55% to about 80% of the amount of the corresponding mineral, including the amount of the corresponding mineral. From about 60% to about 75%, from about 60% to about 70%, from about 60% to about 65°/◦ and especially about 6% by weight (both in unit volume). In such embodiments, the low micronutrient infant formula typically comprises at least 25%, at least 50%, at least 60%, at least 75%, at least 80. /. At least 90% and 100% of the minerals are about 55°/of the amount of the corresponding mineral. The amount to about 803⁄4 is included in the infant formula (in units of volume «10). In other embodiments, at least 10% of the low micronutrient infant formula includes at least 25% and at least 50. /. , at least 6%, at least 75%, at least 80%, at least 90%, and 100% of the minerals are included in the infant formula in an amount of from about 60% to about 7% by weight of the corresponding minerals (in units) Volume meter). Low micronutrient infant formulas such as shai may include, for example, Day 3-9 infant formula. In some embodiments wherein the micronutrient comprises a vitamin, the vitamin is included in the low amount of 16200.doc -24 - 201233333 nutrient infant formula (in terms of unit volume) in an amount of from about 30% to about 8% by weight of the corresponding vitamin. ) 'includes about 30 ° / of the corresponding vitamin amount. Up to about 65°/. From about 55% to about 80%, from about 40% to about 70%, from about 40% to about 50%, and from about 60% to about 70% (both in unit volume). Typically, at least 45% of the low micronutrient infant formula of the present invention comprises at least 50%, at least 60%, at least 70%, at least 8%, at least 85%, at least 90°. And 1〇〇. /. The vitamin is included in the infant formula (in unit volume) in an amount from about 3% to about 8〇0/〇 of the conventional vitamin amount. In other embodiments, the vitamin is included in the low micronutrient infant formula (in terms of unit volume) in an amount of from about 3 〇0/〇 to about 650 % of the conventional vitamin amount, including the amount of the corresponding corresponding vitamin amount. 3 5% to about 60%, about 40% to about 50°/. From about 40% to about 45% and especially about 40% (both in unit volume). In such embodiments, at least 1% of the vitamins in the low micronutrient infant formula typically comprise at least 25%, at least 50%, at least 60%, at least 75%, at least 80°/. At least 90% and 100°/. The vitamin is included in the infant formula (in unit volume) in an amount from about 30% to about 65% of the conventional vitamin amount. In other embodiments, at least 〇% of the vitamins in the low micronutrient infant formula, including at least 25%, at least 50%, at least 60%, at least 75%, and at least 80% of the vitamins are about 4% by weight of the conventional vitamins. An amount of up to about 5% is included in the infant formula (in unit volume). Such low micronutrient infant formulas may include, for example, Day 1-2 infant formula. In other embodiments, the vitamin is included in the low micronutrient infant formula (in unit volume) in an amount of from about 55 〇/〇 to about 80% of the conventional vitamin amount, including about 6 习 of the corresponding vitamin amount. % to about 75%, from about 6 〇〇 / 〇 to about 70%, from about 60% to about 65% and especially about 6% by weight (both in units of volume p 161200.doc -25 - 201233333 in these embodiments) Typically, at least 10% of low micronutrient infant formulas include at least 25%, at least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100% of the vitamins are about 55% of the conventional vitamins. Up to about 80% of the amount is included in the infant formula (in other embodiments, at least 1% in the low micronutrient infant formula, including at least 25°/., at least 50%, at least 60%, at least 75 %, at least 80% and at least 90°. The vitamin is included in the infant formula (in unit volume) in an amount from about 6% to about 7% by weight of the corresponding vitamin. The low micronutrient infant formula can be Includes, for example, Day 3-9 Infant Formula. Suitable microbatches that can be included in the infant formula of the present invention. The hormone includes vitamins or related nutrients, minerals and combinations thereof. Non-limiting examples of suitable vitamins include vitamin A, vitamin D, vitamin E, vitamin κ, vitamin B1, vitamin B2, pyridoxine, vitamin B5, vitamin B6, Vitamin B12, niacin, folic acid, pantothenic acid, biotin, vitamin C, gallstones, inositol, ascorbic acid, salts and derivatives thereof, and combinations thereof. Non-limiting, suitable minerals that may be included in the infant formula of the present invention Examples include calcium, phosphorus, magnesium, iron, zinc, manganese, steel, iodine, sodium, bell, turn, chromium, chloride, fluoride, ί, and combinations thereof. Any infant formula can be formulated with the disclosure disclosed herein. Low micronutrient content 'includes sterilized dad sterilization and aseptically sterilized ready-to-eat nutrient liquids, concentrated nutrient liquids, and nutritional powders. Macronutrients In addition to the micronutrients described herein, the infant formula of the present invention may also comprise one or more macronutrients. Macronutrients include protein and lipids 161200.doc • 26· 201233333 Fat, carbohydrates and combinations thereof. The macronutrients in the formula include any protein, fat, carbohydrate or source thereof known or otherwise suitable for use in oral nutritional products, the restriction being that the macronutrient can be safely and effectively administered orally to the infant and otherwise formulated with the infant. The other ingredients are compatible. Although the total concentration or amount of protein, moon fat and slave compound may be different depending on the product form (eg powder or ready-to-feed liquid) and the desired user's target for the sake of food, 'but the concentration or amount Usually within one of the specific ranges described in the table below (each term is preceded by the term "about"), including any other essential fat, protein and/or carbohydrate component described herein. For the powder examples, the content in the table below is the amount after the powder is reconstituted. Table c Nutrients (g/100 mL) Example A Example B 0.6 to 0.9 Protein 0.55.1.0 Fat 1.25.2.5 1.4 to 2.3 Carbohydrate 2.75.6.5 3.1 to 6.1 The total concentration or amount of protein, fat and water compound It can be seen whether the infant formula is for the 1-2 day formula or the 3-9 day formula. The concentrations of protein, fat and carbohydrate in Formulations 1 - 2 and Days 3-9 are most often formulated in any of the specific ranges described in the table below (the terms "about" are added before each value) , including any other essential fat, protein, and/or carbohydrate components described herein. For the powder embodiment, the content in the table below is the content after recovery. 161200.doc •27- 201233333

表D 第1-2天配方 第3-9天配方 營養物(g/100 mL) 實例C 實例D 實例E 實例F 蛋白質 0.50 至 0.75 0.58 至 0.72 0.76 至 1.0 0.85 至 0.98 脂肪 1.25.1.7 1.4 至 1.6 1.8 至 2.5 2.0 至 2.2 碳水化合物 2.7 至 4.0 2.9 至 3.6 4.1 至 6.5 4.9 至 6.3 或者或另外，嬰兒配方（無論粉末配方或即食型液體或 濃縮液體）中碳水化合物、脂肪及蛋白質之含量或量亦可 表徵為嬰兒配方中之總熱量百分比。本發明之嬰兒配方中 之該等常量營養素最通常經調配屬於下表中描述熱量範圍 中之任一者内（各數值前均加上術語「約」）。Table D Day 1-2 Formulation Day 3-9 Formula Nutrient (g/100 mL) Example C Example D Example E Example F Protein 0.50 to 0.75 0.58 to 0.72 0.76 to 1.0 0.85 to 0.98 Fat 1.25.1.7 1.4 to 1.6 1.8 to 2.5 2.0 to 2.2 Carbohydrates 2.7 to 4.0 2.9 to 3.6 4.1 to 6.5 4.9 to 6.3 or alternatively, the amount or amount of carbohydrates, fats and proteins in infant formula (whether in powder formula or ready-to-feed liquid or concentrated liquid) It can be characterized as the percentage of total calories in the infant formula. The macronutrients in the infant formula of the present invention are most often formulated in any of the ranges of calories described in the table below (each term is preceded by the term "about").

表E 營養物(總熱量％) 實例G 實例Η 實例I 碳水化合物 2至96 10 至 75 30 至 50 蛋白質 2至96 5至70 15 至 35 脂肪 2至96 20 至 85 35 至 55 實例J 實例Κ 實例L 碳水化合物 25 至 50 25 至 50 35 至 50 蛋白質 10 至 30 5至30 7.5 至 25 脂肪 1至20 2至20 30 至 60 蛋白質 除本文中所描述之微量營養素外，本發明之嬰兒配方亦 可包含蛋白質。本發明之嬰兒配方中可包括任何已知或其 他適用之蛋白質或蛋白質源，限制條件為該等蛋白質適用 於傲養嬰兒且尤其為新生兒。 用於嬰兒配方中之合適蛋白質或其來源之非限制性實例 包括水解、部分水解或非水解蛋白質或蛋白質源，其可來 161200.doc -28· 201233333 源於任何已知或其他合適來源、，諸如乳（例如路蛋白、乳 清）、動物（例如肉、魚）、榖類（例如稻、玉蜀黍）、.植物（例 如大丑）或其組合。該等蛋白質之非限制性實例包括如本 文中所描述之乳蛋白分離物、乳蛋白濃縮物、酪蛋白分離 物、同度水解酪蛋白、乳清蛋白、酪蛋白鈉或酪蛋白鈣、 全脂牛乳、部分或完全脫脂乳、大豆蛋白分離物、大豆蛋 白濃縮物等。本文中使用之蛋白質亦可包括已知用於營養 產品中之游離胺基酸或完全或部分地由已知用於營養產品 中之游離胺基酸替代，該等游離胺基酸之非限制性實例包 括L-丙胺酸、L-天冬胺酸、l·麵胺酸、甘胺酸、l-組胺 酸、L•異白胺酸、L_白胺酸、L-***酸、L-脯胺酸、L-絲胺酸、L-蘇胺酸、纈胺酸、L_色胺酸、L_麵醯胺酸、 L-酪胺酸、L-甲硫胺酸、L_半胱胺酸、牛磺酸、L_精胺 酸' L-肉驗及其組合。 脂肪 除本文中所描述之微量營養素外，本發明之嬰兒配方亦 可包含脂肪源。用於本文中揭示之嬰兒配方中之合適脂肪 源包括任何適用於口服營養產品中且與該等產品之要素及 特徵相容之脂肪或脂肪源，限制條件為該等脂肪適用於餵 養嬰兒。 用於本文中所描述之嬰兒配方中之合適脂肪或其來源之 非限制性實例包括椰子油、分餾椰子油、大豆油、玉米 油、撖欖油、紅花子油、高油酸紅花子油、高GLA紅花子 油、油酸、MCT油（中鏈三酸甘油酯）、葵花籽油、高油酸 161200.doc -29- 201233333 葵花籽油、結構化三酸甘油酯、棕櫚油及棕櫚仁油、棕櫚 油精（palm olein)、菜籽油、亞麻籽油、琉璃苣籽油、月見 草油、黑醋栗籽油、轉殖基因油來源、水產油（例如金槍 魚、沙丁魚）、魚油、真菌油、海藻油棉籽油及其組 合。在-個實施例中，合適脂肪或其來源包括油及油換合 物，包括長鏈多不飽和脂肪酸（lc_pufa)。可包含之一些 非限制性特定多不飽和酸包括例如二十二碳六烯酸 (DHA)、一十奴四烯酸（ARA)、二十碳五烯酸（EpA)、亞麻 油酸（LA)及其類似物。非限制性二十碳四烯酸及二十二碳 六稀酸之來源包括水產油、來源於蛋類之油、冑菌油、海 藻油及其組合。 碳水化合物 本發明之嬰兒配方可包含任何適用於口服營養產品（諸 如嬰兒配方）中且與該等產品之要素及特徵相容之碳水化 合物。 適用於本文中所描述之嬰兒配方中之碳水化合物或其來 源之非限制性實例可包括麥芽糊精；水解、完整或改質之 殿粉或玉米殿粉；葡萄糖聚合物；玉米㈣；玉米糖裝固 體’來源於稻米之碳水化合物；稻米糖漿；來源於豌豆之 碳水化合物；來源於馬铃薯之碳水化合物；木薯；蔗糖； 葡萄糖；果糖；乳糖；高果糖玉米糖毁；蜂蜜；糖醇（例 如麥芽糖醇、赤藻糖醇、山梨糖醇）；人工甜味劑（例如蔗 糖素、乙醯磺胺酸鉀、甜菊）；冑消化寡醣，諸如果寡醣 (FOS)，及其組合。在一個實施例中，碳水化合物可包括 161200.doc 201233333 DE值小於20之麥芽糊精。 其他視情況可選成分 本發明之嬰兒配方亦可進一步包含可改良產品之物理、 化學、美學或加工特徵或在用於目標群體時充當醫藥或其 他營養組分之其他視情況選用之成分。多種該等視情況選 用之成分為已知或以其他方式適用於醫藥食品或其他營養 產品或醫藥劑型中且亦可用於本文中之組合物申，限制條 件為該等視情況選用之成分可安全經口投與且與所選產品 形式中之必需及其他成分相容。 該4視情況選用之成分之非限制性實例包括防腐劑、抗 氧化劑、乳化劑、緩衝劑、果寡醣、半乳募醣、人乳寡醣 及其他益菌助生質（prebi〇tic)、醫藥活性物、本文中所描 述之其他營養物、著色劑、香料、增稠劑及穩定劑、乳化 劑、潤滑劑、類胡蘿蔔素（例如β_胡蘿蔔素、玉米黃素、葉 黃素、番茄紅素）等及其組合。 本文中所描述之粉末嬰兒配方可包括流動劑或抗結塊劑 以延緩粉末隨時間推移而凝塊或結塊且使粉末實施例易於 自其容器流動。任何已知或以其他方式適用於營養粉末或 產品形式中之流動劑或抗結塊劑均可適用於本文中其非 限制實例包括磷酸三鈣、矽酸鹽及其組合。營養產品中流 動劑或抗結塊劑之濃度視產品形式、其他所選成分、所需 流動性質等不同，但最通常在營養產品之約〇ι重量。/。至約 4重量°/。範圍内’包括約〇5重量％至約2重量％。 嬰兒配方中亦可包括穩定劑。任何已知或以其他方式適 161200.doc •31· 201233333 用於營養產。〇中之穩定劑亦適用於本文中’其一些非限制 性實例包括樹膠，諸如三仙膠。穩定劑可占嬰兒配方之約 0.1重量％至約5.0重量％，包括約〇 5重量％至約3重量0/〇， 包括約0.7重量％至約1 · 5重量〇/0。 穩定性 本發明之低熱量、低微量營養素液體嬰兒配方與低熱 量、高微量營養素配方相比有利地呈現物理屬性改良，包 括穩定性改良。液體嬰兒配方之物理穩定性問題通常在配 方於使用前長期儲存時出現。在此期間，配方之組分（例 如脂肪）通常與水性組分分離。嬰兒配方之組分亦可能自 懸浮液沈降’從而在配方容器底部形成沈降物。儘管可藉 由搖動配方以再混合配方組分來矯正此相分離及沈降，但 該相分離及沈降通常引起消費者對產品之接受度極大降 低。 現發現低熱量液體嬰兒配方之微量營養素含量可影響嬰 兒配方之穩定性。詳言之，本發明之低熱量、低微量營養 素液體嬰兒配方與低熱量、高微量營養素配方相比在配方 存放期期間有利地呈現較少沈降及較少分離。 蛋白質負載 可使用多種量測法驗證液體嬰兒配方之穩定性。舉例而 言’一種方法為可藉由量測蛋白質負載量來測定液體嬰兒 配方之穩定性。蛋白質負載量可表示為對嬰兒配方進行高 速離心後形成之乳油層之蛋白質百分比（每100公克乳膏劑 層中蛋白質公克數）。適用於測定蛋白質負載量之技術詳 161200.doc •32· 201233333 細描述於本揭示案之實例中。 液體嬰兒配方乳液之穩定性通常隨蛋白質負載量增加而 增加。現發現低熱量、低微量營養素殺菌釜滅菌液體嬰兒 配方與低熱量、高微量營養素殺菌爸滅菌液體嬰兒配方相 比具有較高蛋白質負載量。在第天殺菌蚤滅菌嬰兒配 方及第3-9天殺菌爸滅菌嬰兒配方中均發現此情況。 因此’在一個態樣中’本發明係關於低熱量、低微量營 養素液體嬰兒配方’其與低熱量、高微量營養素嬰兒配方 相比蛋白質負載量增加。低熱量、低微量營養素液體嬰兒 配方較佳為殺菌釜滅菌之即食型（RTF)配方。在其中低熱 量、低微量營養素液體嬰兒配方為第1·2天嬰兒配方之實 施例中’嬰兒配方之蛋白質負載量將通常為至少約5.0%， 包括約5.0%至約7.0%、約5.5%至約6.5%、約5.7%至約 6.1%且尤其為約5.9%。 在其中低熱量、低微量營養素液體嬰兒配方為第3-9天 嬰兒配方之實施例中，嬰兒配方之蛋白質負載值將通常為 至少約6.0%，包括約6_0%至約8.0%、約6.5%至約7.5%、 約6.7°/。至約7.1%且尤其為約6.9%。低熱量、低微量營養素 液體嬰兒配方較佳經殺菌釜滅菌。 粒徑 另一種可用於驗證液體嬰兒配方之穩定性的量測法為存 在於嬰兒配方中顆粒之粒徑分佈及平均粒徑。可使用此項 技術中已知的任何技術測定粒徑分佈及平均粒徑。本揭示 案之實例中描述之一種技術涉及使用光散射機器（例如 16l200.doc • 33- 201233333Table E Nutrients (% of total calories) Example G Example 实例 Example I Carbohydrate 2 to 96 10 to 75 30 to 50 Protein 2 to 96 5 to 70 15 to 35 Fat 2 to 96 20 to 85 35 to 55 Example J Example Example L Carbohydrate 25 to 50 25 to 50 35 to 50 Protein 10 to 30 5 to 30 7.5 to 25 Fat 1 to 20 2 to 20 30 to 60 Protein In addition to the micronutrients described herein, the infant formula of the present invention is also May contain protein. Any known or otherwise suitable source of protein or protein may be included in the infant formula of the present invention with the proviso that such proteins are suitable for use in babies and especially in newborns. Non-limiting examples of suitable proteins or sources thereof for use in an infant formula include hydrolyzed, partially hydrolyzed or non-hydrolyzed protein or protein sources, which may be derived from any known or other suitable source, 161200.doc -28 - 201233333, Such as milk (such as road protein, whey), animals (such as meat, fish), mites (such as rice, maize), plants (such as large ugly) or a combination thereof. Non-limiting examples of such proteins include milk protein isolates, milk protein concentrates, casein isolates, homozygous casein, whey proteins, casein sodium or casein calcium, full fats as described herein. Milk, partially or completely skimmed milk, soy protein isolate, soy protein concentrate, and the like. The protein used herein may also include free amino acids known for use in nutritional products or may be replaced, in whole or in part, by free amino acids known for use in nutritional products, such non-limiting free amino acids. Examples include L-alanine, L-aspartic acid, l- faceamine, glycine, l-histamine, L•isoleucine, L-leucine, L-phenylalanine, L- Proline, L-serine, L-threonine, valine, L_tryptophan, L-facial acid, L-tyrosine, L-methionine, L-cysteine Amino acid, taurine, L_arginine 'L-meat test and combinations thereof. Fat In addition to the micronutrients described herein, the infant formula of the present invention may also comprise a source of fat. Suitable fat sources for use in the infant formula disclosed herein include any fat or fat source suitable for use in oral nutritional products and compatible with the elements and characteristics of such products, with the proviso that such fats are suitable for feeding infants. Non-limiting examples of suitable fats or sources thereof for use in the infant formulas described herein include coconut oil, fractionated coconut oil, soybean oil, corn oil, eucalyptus oil, safflower oil, high oleic safflower oil, High GLA safflower oil, oleic acid, MCT oil (medium chain triglyceride), sunflower oil, high oleic acid 161200.doc -29- 201233333 sunflower oil, structured triglyceride, palm oil and palm kernel Oil, palm olein, rapeseed oil, linseed oil, borage seed oil, evening primrose oil, blackcurrant seed oil, source of genetic oil, aquatic oil (eg tuna, sardines), fish oil, fungi Oil, seaweed oilseed oil and combinations thereof. In one embodiment, suitable fats or sources thereof include oils and oils, including long chain polyunsaturated fatty acids (lc_pufa). Some non-limiting specific polyunsaturated acids which may be included include, for example, docosahexaenoic acid (DHA), decenoic acid (ARA), eicosapentaenoic acid (EpA), linoleic acid (LA). ) and its analogues. Sources of non-limiting eicosatetraenoic acid and docosahexaenoic acid include aquaculture oils, oils derived from eggs, sputum oils, algae oils, and combinations thereof. Carbohydrates The infant formula of the present invention may comprise any carbohydrate compound suitable for use in oral nutritional products, such as infant formulas, and compatible with the elements and characteristics of such products. Non-limiting examples of carbohydrates or sources thereof suitable for use in the infant formulas described herein may include maltodextrin; hydrolyzed, intact or modified temple flour or corn house flour; glucose polymer; corn (four); corn Sugar-loaded solids 'from carbohydrates of rice; rice syrup; carbohydrates derived from peas; carbohydrates derived from potato; cassava; sucrose; glucose; fructose; lactose; high fructose corn sugar; honey; (eg, maltitol, erythritol, sorbitol); artificial sweeteners (eg, sucralose, potassium sulfamate, stevia); digestible oligosaccharides, oligosaccharides (FOS), and combinations thereof. In one embodiment, the carbohydrate may comprise 161200.doc 201233333 maltodextrin having a DE value of less than 20. Other Optional Ingredients The infant formula of the present invention may further comprise other optional ingredients which modify the physical, chemical, aesthetic or processing characteristics of the product or act as a pharmaceutical or other nutrient component when used in the target population. A plurality of such optional ingredients are known or otherwise suitable for use in pharmaceutical or other nutritional products or pharmaceutical dosage forms and may also be used in the compositions herein, with the proviso that the ingredients selected as such may be safe. It is administered orally and is compatible with the necessary and other ingredients in the selected product form. Non-limiting examples of such optional ingredients include preservatives, antioxidants, emulsifiers, buffers, fructooligosaccharides, galacto-sugar, human milk oligosaccharides, and other prebi〇tic, Pharmaceutical actives, other nutrients, colorants, fragrances, thickeners and stabilizers, emulsifiers, lubricants, carotenoids (eg, beta-carotene, zeaxanthin, lutein, tomato) described herein Red pigment) and the like. The powdered infant formula described herein can include a flow or anti-caking agent to delay the agglomeration or agglomeration of the powder over time and to facilitate the flow of the powder embodiment from its container. Any flow or anti-caking agent known or otherwise suitable for use in a nutritional powder or product form may be suitable for use herein, non-limiting examples of which include tricalcium phosphate, citrate, and combinations thereof. The concentration of the fluid or anti-caking agent in the nutritional product will vary depending on the product form, other selected ingredients, the desired flow properties, etc., but is most typically about the weight of the nutritional product. /. Up to about 4 weights /. Within the range 'includes from about 5% by weight to about 2% by weight. Stabilizers may also be included in the infant formula. Any known or otherwise suitable 161200.doc •31· 201233333 for nutritional production. Stabilizers in sputum are also suitable for use herein' some non-limiting examples include gums such as sinica. The stabilizer may comprise from about 0.1% to about 5.0% by weight of the infant formula, including from about 5% by weight to about 3% by weight, including from about 0.7% by weight to about 1.7% by weight. Stability The low calorie, low micronutrient liquid infant formula of the present invention advantageously exhibits improved physical properties, including improved stability, as compared to low heat, high micronutrient formulations. Physical stability issues with liquid infant formulas usually occur when the formulation is stored for long periods of time prior to use. During this time, components of the formulation, such as fat, are usually separated from the aqueous component. The components of the infant formula may also settle from the suspension' to form a sediment at the bottom of the formula container. Although this phase separation and sinking can be corrected by shaking the formulation to remix the formulation components, the phase separation and sinking typically cause the consumer's acceptance of the product to be greatly reduced. It has been found that the micronutrient content of low calorie liquid infant formula can affect the stability of infant formula. In particular, the low calorie, low micronutrient liquid infant formula of the present invention advantageously exhibits less sedimentation and less separation during the formulation shelf life than the low calorie, high micronutrient formulation. Protein Loading A variety of measurements can be used to verify the stability of a liquid infant formula. By way of example, one method is to determine the stability of a liquid infant formula by measuring the protein loading. The protein loading can be expressed as the percentage of protein in the cream layer formed by high speed centrifugation of the infant formula (grams of protein per 100 grams of cream layer). Technical details applicable to the determination of protein loading are detailed in the examples of this disclosure. 161200.doc • 32· 201233333. The stability of liquid infant formula emulsions generally increases with increasing protein loading. It has been found that low-calorie, low-micronutrient sterilizing liquid sterilized liquid infant formula has a higher protein load than low-calorie, high-micronutrient sterilized dad sterilized liquid infant formula. This was observed in the first day of sterilized sterilized infant formula and the 3rd-9th sterilized dad sterilized infant formula. Thus, 'in one aspect, the present invention relates to a low calorie, low micronutrient liquid infant formula' which has an increased protein loading compared to a low calorie, high micronutrient infant formula. The low-calorie, low-micronutrient liquid infant formula is preferably a sterilized, ready-to-eat (RTF) formulation. In embodiments where the low calorie, low micronutrient liquid infant formula is a Day 1 2 infant formula, the protein loading of the infant formula will typically be at least about 5.0%, including from about 5.0% to about 7.0%, about 5.5%. To about 6.5%, from about 5.7% to about 6.1% and especially about 5.9%. In embodiments wherein the low calorie, low micronutrient liquid infant formula is a 3-9 day infant formula, the infant formula will typically have a protein loading value of at least about 6.0%, including from about 6% to about 8.0%, about 6.5%. To about 7.5%, about 6.7 ° /. To about 7.1% and especially about 6.9%. Low-calorie, low-micronutrient liquid infant formula is preferably sterilized by autoclave. Particle Size Another measure that can be used to verify the stability of a liquid infant formula is the particle size distribution and average particle size of the particles present in the infant formula. The particle size distribution and average particle size can be determined using any technique known in the art. One technique described in the examples of the present disclosure relates to the use of light scattering machines (e.g., 16l200.doc • 33-201233333)

Beckman Coulter LS 13 320) ’其使用多波長光源量測懸浮 於液體嬰兒配方樣品中之顆粒之粒徑分佈。亦可使用其他 合適技術。 液體嬰兒配方乳液之穩定性通常隨粒徑減小而增加。現 發現本發明之低熱量、低微量營養素第天殺菌釜滅菌 液體嬰兒配方與低熱量、咼微量營養素第1-2天殺菌爸滅 菌液體嬰兒配方相比具有更多數目的小顆粒且存在於配方 中顆粒之平均粒徑較小。 因此，在一個態樣中，本發明係關於低熱量、低微量營 養素液體嬰兒配方，其與低熱量、高微量營養素液體嬰兒 配方相比存在於配方中顆粒之平均粒徑較小。低熱量、低 微量營養素液體嬰兒配方較佳為殺菌釜滅菌RTF配方，且 更佳為第1-2天殺菌釜滅菌液體嬰兒配方。在其中低熱 量、低微量營養素液體嬰兒配方為第1_2天嬰兒配方之實 施例中’存在於嬰兒配方中顆粒之平均粒徑將通常為約 0.1 μιη至約 1.0 μπι’ 包括約 0.15 μηι至約 〇.8 μιη及約 0.15 μηι至約 0.7 μιη。 通常’對於本發明之低熱量、低微量營養素第天液 體嬰兒配方，存在於嬰兒配方中之至少約5〇%(包括約50〇/〇 至約100%及約50%至約70%)顆粒之粒徑（直徑）將為約〇· 15 μιη至約 0.8 μιη。 乳油分離速度（Creaming Velocity) 另一種可用於驗證液體嬰兒配方之穩定性的量測法為乳 油分離速度。乳油分離速度量測液體樣品（在此情況下， 161200.doc •34· 201233333 嬰兒配方）中顆粒移動之速率且可預示嬰兒配方在長期靜 置或離心後形成乳油層之能力。可使用以下方程式計算乳 油分離速度： 2 PflukBeckman Coulter LS 13 320) ' uses a multi-wavelength source to measure the particle size distribution of particles suspended in a liquid infant formula sample. Other suitable techniques can also be used. The stability of liquid infant formula emulsions generally increases with decreasing particle size. It has been found that the low-calorie, low-micronutrient-free sterilized liquid infant formula of the present invention has a larger number of small particles and is present in the formula than the low-calorie, bismuth micronutrient 1-2 day sterilization sterilized liquid infant formula. The average particle size of the medium particles is small. Thus, in one aspect, the present invention is directed to a low calorie, low micronutrient liquid infant formula that has a smaller average particle size in the formulation than a low calorie, high micronutrient liquid infant formula. The low-calorie, low-micronutrient liquid infant formula is preferably a sterilization-sterilized RTF formulation, and more preferably a 1-2 day sterilization-sterilized liquid infant formula. In embodiments wherein the low calorie, low micronutrient liquid infant formula is a 1st day infant formula, the average particle size of the particles present in the infant formula will typically range from about 0.1 μιη to about 1.0 μπιη including about 0.15 μηι to about 〇 .8 μιη and about 0.15 μηι to about 0.7 μιη. Typically, for the low calorie, low micronutrient day liquid infant formula of the present invention, at least about 5% (including from about 50 〇 to about 100% and from about 50% to about 70%) of the granules present in the infant formula The particle size (diameter) will be from about 15 μm to about 0.8 μm. Creaming Velocity Another measure that can be used to verify the stability of a liquid infant formula is the rate of cream separation. The emulsification separation rate measures the rate at which the liquid sample moves (in this case, 161200.doc •34·201233333 infant formula) and predicts the ability of the infant formula to form a cream layer after long periods of standing or centrifugation. The separation rate can be calculated using the following equation: 2 Pfluk

Pparticle ^^2 7 其中：Pparticle ^^2 7 where:

Vcream為乳油分離速度 Pfluid為配方在"'度 P p a r t i c 1 e為顆粒祖度 η為配方黏度 R為平均粒徑 g為重力加速度。 液體嬰兒配方乳液之穩定性通常隨乳油分離速度降低而 增加。現發現本發明之低熱量、低微量營養素第1_2天殺 菌爸滅菌液體嬰兒配方與低熱量、高微量營養素第1_2天 殺菌釜滅菌液體嬰兒配方相比具有較低乳油分離速度。 因此，在一個態樣中’本發明係關於低熱量、低微量營 養素液體嬰兒配方，其與低熱量、高微量營養素嬰兒配方 相比具有低乳油分離速度。低熱量、低微量營養素液體嬰 兒配方較佳為殺菌爸滅菌RTF配方，且更佳為第1 _2天殺菌 爸滅菌液體嬰兒配方。在其中低熱量、低微量營養素液體 嬰兒配方為第1-2天嬰兒配方之實施例中，嬰兒配方之乳 油分離速度將通常為約5.0公分/天或5.0公分/天以下，包括 約1.0公分/天至約5.0公分/天、約3·〇公分/天至約3 5公分/ 天且尤其為約3·2公分/天。 161200.doc •35· 201233333 顏色 本發明之低熱量、低微量營養素液體嬰兒配方與低熱 量、高微量營養素配方相比亦有利地呈現顏色改良。 液體嬰兒配方含有多種營養物，其在調配、加工及儲存 期間可能相互作用。該等相互作用可使配方顏色扭曲為灰 色、米色或其他類似變色。該等變色通常引起消費者對產 品之接受度極大降低，消費者通常偏愛光亮、發白色的產 品。 一種可用於評估嬰兒配方之顏色特徵之技術為艾格壯顏 色計分（Agtron color score)。本文中所用艾格壯計分係使 用 Agtron 45分光光度計（可自 Agtron Inc·，Reno，Nevada獲 得）藉由習知技術量測。艾格壯計分為自各嬰兒配方之表 面反射之能量（光）百分比之量測值。配方表面顏色反射性 越強或越亮’則艾格壯計分越高。該等計分在〇(黑色）至 100(白色）範圍内。 現發現低熱量液體嬰兒配方之微量營養素含量可影響配 方顏色。詳言之，本發明之低熱量、低微量營養素液體嬰 兒配方與低熱量、高微量營養素配方相比具有更亮、更白 的顏色（如由艾格壯計分定義）。在殺菌釜滅菌及無菌滅菌 - 低熱量、低微量營養素液體配方中均發現此情況。亦不僅 ·_ 在剛調配後’且亦在長時間後（在一些情況下，產品調配 後至少9個月）觀測到低熱量、低微量營養素液體嬰兒配方 之顏色改良。 因此，在一個態樣中，本發明係關於低熱量、低微量營 161200.doc -36 · 201233333 養素第w天液體嬰兒配方，其調配後(調配…天内)之艾 格壯計分為至少約45，包括約45至約6〇及約47至約55。配 方較佳為殺菌爸滅菌RTF配方。在其他實施例中，配方在 調配後兩個月之艾格壯計分為至少約4〇，包括約4〇至約 50 ;在調配後四個月之艾格壯計分為至少約37，包括約利 至約50;在調配後六個月之艾格壯計分為至少約37，包括 約37至約50;且在調配後九個月之艾格壯計分為至少約 35，包括約35至約45。 在另一態樣中，本發明係關於低熱量、低微量營養素第 3-9天液體殺菌釜滅菌嬰兒配方，其調配後之艾格壯計分 為至少約42，包括約42至約55及約45至約52。在其他實施 例中，配方在調配後三個月之艾格壯計分為至少約4〇，包 括約40至約50 ;且在調配後六個月之艾格壯計分為至少約 4〇，包括約40至約50。 在另一態樣中’本發明係關於低熱量、低微量營養素第 3-9天液體無菌滅菌嬰兒配方，其調配後之艾格壯計分為 至少約58 ’包括約58至約65及約60至約62。在其他實施例 中’配方在調配後兩個月之艾格壯計分為至少約55，包括 約55至約62 ;在調配後六個月之艾格壯計分為至少約55， 包括約55至約60 ;且在調配後九個月之艾格壯計分為至少 約52，包括約52至約55。 緩衝能力 本發明之低熱量嬰兒配方（具有高或低微量營養素含量） 與全熱量配方相比亦有利地呈現改良之緩衝能力。 161200.doc .37· 201233333 咸信人類母乳含有某些促進有利腸細菌群落（明確言 之，雙又桿菌發育之因子，雙又桿菌可 阻止病原微生物增殖。咸信嬰兒腸道中雙又桿菌之生長係 由人類母乳之物理化學性質（尤其其高乳糖含量（其為雙叉 才干菌之受質）、其低蛋白含量及其低緩衝能力）促進。此 外，人乳之低緩衝能力可使嬰兒腸胃道（GI)中之天然酸度 更有效地使經口攝取之病原體失活。在一些情況下，嬰兒 配方可具有相對較高緩衝能力，其可能不完全有利於雙又 桿菌之生長且可能潛在影響嬰兒腸胃道之天然酸度。因 此，一些配方飯養之嬰兒與母乳飯養嬰兒相比可能經歷更 多的腸胃道感染事件。 現發現嬰兒配方之緩衝能力與配方之能量含量有關。明 確s之，已發現嬰兒配方之緩衝能力隨能量含量降低而降 低。因此本發明之低熱量嬰兒配方與全熱量嬰兒配方相比 有利地具有改良（亦即較低）之緩衝能力，且在一些實施例 中’其緩衝能力低於人乳。因此，本發明之低熱量嬰兒配 方可用於調節嬰兒且尤其新生兒之胃液酸度，減少嬰兒腸 胃道中病原微生物生長、促進有益微生物（諸如雙又桿菌） 生長且提高使經口攝取之病原體失活之有效性。 緩衝能力通常係指液體抵抗pH值變化之能力。用於表示 本發明嬰兒配方之緩衝能力的量度有很多種。舉例而言， 嬰兒配方之緩衝能力可表示為在向嬰兒配方（或向粉末嬰 兒配方實施例之復原配方）中添加鹽酸（HC1)後氫離子漢度 ([H+])之增加量。明確言之，緩衝能力係以向1〇〇 mL配方 161200.doc • 38 · 201233333 中添加5mm〇丨hci後[H+]之增加量表示，或以向丨⑽爪^己 方中添加5.5。mm<)1 HC1(或向5。社配方中添加2 75腿〇1 HC1)後[H+]之增加量表示。 本發明之低熱量嬰兒配方之緩衝能力（以向1〇〇 配方 中添加5 mmol Ha後之[H+]表示）可為至少約2〇 mM，包 括至少約5.0 mM、至少約7·〇 mM、至少約1〇.〇 mM、至少 約13.0 及至少約17.〇 mM，及/或約2 〇 mM至約25 〇 mM，包括約5·〇 mM至約21 〇 mM及約i〇 〇 至約21 〇 mM。嬰兒配方可為復原粉末配方（殺菌釜滅菌或無菌滅 菌）且可為第1_2天或第3·9天配方。在―個實施例中，低熱 量嬰兒配方為第3-9天配方且其緩衝能力（表示為向丨〇() m]L 配方中添加5 mmol HC1後之[H+])為至少約2.0 mM，包括 至少約5.0 mM、至少約7·〇福及至少約9〇碰，及/或約 2.0 mM至約13.0 mM，包括約8·〇 mM至約n 〇 mM。在另 一實施例中，低熱量嬰兒配方為第丨_2天配方且其緩衝能 力（表示為向100 mL配方中添加5 mm〇1 Ηα後之[H+])為至 〉、約8.0 mM，包括至少約1〇 〇 mM、至少約13 〇 、至 少約17·〇 mM及至少約20.0 mM，及/或約8 〇 mM至約25 〇 mM，包括約8.〇 mM至約21 〇 mM，約13 〇爪以至約2〇 〇 mM及約 17.0 mM至約 20.0 mM。 或者，嬰兒配方之緩衝能力可表示為在向嬰兒配方（或 向粉末嬰兒配方實施例之復原配方）中添加配方之pH 值之降低。明確言之，緩衝能力可表示為向1〇〇 mL配方中 添加5.5〇 mmol HC1(或向5〇 mL配方中添加2 75麵〇1 HC1) 161200.doc -39- 201233333 後之pH值之降低。 因此’在一個實施例中，本發明之低熱量嬰兒配方為粉 末嬰兒配方且其在復原後之緩衝能力（表示為向1〇〇 mL復 原配方中添加5.50 mmol HC1後配方之pH值之降低）為至少 約4.20，包括至少約冬5〇及至少約4 8〇。在其中低熱量嬰 兒配方為殺菌釜滅菌RTF配方之另一實施例中，緩衝能力 (表示為向50 mL配方中添加2.75 mmol HC1後配方之pH值 之降低）為至少約4.20，包括至少約4.30 »在其中低熱量嬰 兒配方為無菌滅菌RTF配方之又一實施例中，緩衝能力（表 示為向100 mL配方中添加5.50 mmol HC1後配方之pH值之 降低）為至少約4.60，包括至少約4.70。 緩衝能力之另一量度為緩衝劑強度。除非另有說明，否 則本發明之嬰兒配方之緩衝強度可表示為使50 mL配方（或 粉末嬰兒配方實施例之復原配方）之pH值自起始pH值（例如 6.0)降至pH 3.0所需之0.1 M HC1之體積。如本文中所用， 術語「低緩衝強度」係指緩衝強度為約1 8 mL或18 mL以 下。緩衝強度（當指示時）在本文中亦表示為使100 mL配方 之pH值自6.0降至3.0所需之HC1之毫莫耳量及使50 mL配方 之pH值自6.0降至3.0所需之HC1之毫莫耳量。 本發明之低熱量嬰兒配方之緩衝強度（表示為使50 mL配 方（或粉末嬰兒配方實施例之復原配方）之pH值自起始pH值 降至pH 3.0所需之0.1 M HC1之毫升量）為約18 mL或18 mL 以下，包括約14 mL或14 mL以下，及/或包括約9 mL至約 1 8 mL，包括約10 mL至約14 mL及約14 mL至約18 mL。在 161200.doc •40· 201233333 一個實施例中，低熱量嬰兒配方為第3_9天配方且其緩衝 強度為約18 mL或18 mL以下’包括約14 mL至約18 mL及 約16 mL至約17 mL。在另一實施例中，低熱量嬰兒配方為 第1-2天配方且其緩衝強度為約14 mL或14 mL以下，包括 約9 mL至約14 mL及約10 mL至約11 mL。人乳之緩衝強度 通常在9 mL至18 mL範圍内。本發明之低熱量嬰兒配方有 利地具有與人乳相當或低於人乳之緩衝強度。 蛋白質水解及消化 本發明之低熱量嬰兒配方（具有高或低微量營養素含量） 與全熱量配方相比亦有利地呈現較快蛋白質水解及消化 率〇 確定食品蛋白質之營養品質之兩種因素為消化率及生物 可用性。通常，嬰兒配方之蛋白質含量高於可見於母乳中 之蛋白質含量。嬰兒配方通常製備為具有較高蛋白質含量 以解決假定的蛋白質消化率較低問題。 此外，在一些情況下，嬰兒配方製備期間使用之方法可 月色在營養方面造成潛在影響，諸如使配方中蛋白質之溶解 度及/或消化率降低。舉例而言，在一些情況下，一些用 於製備濃縮液體及即食型嬰兒配方之長時間熱處理可能潛 在地降低蛋白質消化率。由於暴露於熱，蛋白質變性或聚 集，在一些情況下可能改變其消化率。在高溫下處理乳品 亦可能増加胺基酸與糖之反應，稱為梅納反應（MaiiiaU reaction)。在一些情況下，該等反應可因限制蛋白分解酶 接近而降低胺基酸之生物可用性。因此，一些配方餵養之 161200.doc 201233333 嬰兒可能經歷一些營養物（且尤其為蛋白質）吸收不全。因 此，具有改良之蛋白質消化之嬰兒配方將對已知消化酶 (諸如胃蛋白酶及腸胰酶）含量低於較大嬰兒及成年人之新 生兒尤其有益。 現已發現嬰兒配方中蛋白質之消化（本文中可與術語 「水解」互換使用）之程度（本文中可與術語「速率」互換 使用）與配方之能量含量有關。明確言之，已發現存在於 嬰兒配方中之蛋白質之消化率隨配方之能量含量降低而增 加《本發明之低熱量嬰兒配方與全熱量嬰兒配方相比有利 地具有改良（例如更快）之蛋白質消化率。此可改良嬰兒對 嬰兒配方之耐受性及改良營養物（且尤其為蛋白質）之吸 收。 用於表不蛋白質消化率或程度之量度有許多種。舉例而 言，本發明之嬰兒配方中蛋白質之消化率或程度係以使用 月蛋白_及胰酶（澱粉酶/蛋白酶/脂肪酶）進行活體外腸胃 /肖化或活體外胰酶消化後蛋白質之中值分子量（Mw)表 示。蛋白質MW中值降低表示消化率較快及消化程度增 加。用於該等消化之程序闡述於實例中。 在一些實施例中，本發明之低熱量嬰兒配方之蛋白質消 化率或程度（表示為在如本文中所描述進行活體外腸胃消 化後之蛋白質MW中值）為約950道爾頓（Da)或95〇道爾頓以 下，包括約925 Da或925 Da以下、約85〇 〇&或85〇 Da以 下、約800 Da或800 Da以下及約790 Da479() Da以下。對 於本發明之第3-9天配方，蛋白質消化率或程度（表示為在 161200.doc -42- 201233333 如本文中所描述進行活體外腸胃消化後之蛋白質Mw中值） 通常為約700 Da至約950 Da。對於第u天配方，蛋白質消 化率或程度（表不為在如本文中所描述進行活體外腸胃消 化後之蛋白質MW中值）通常為約825 !^或825 Da以下，包 括約800 Da或800 Da以下、約780 D478〇Da以下、約75〇 Da或750 Da以下及約720 !^或72〇 Da以下。第卜2天配方 之蛋白質消化率或程度通常為約7〇〇Da至約8〇〇Da。 對於第3-9天配方，本發明之低熱量嬰兒配方之蛋白質 消化率或程度（表示為在如本文中所描述進行了丨分鐘活體 外胰酶消化後之蛋白質肘冒中值）為約8〇〇 〇&或8〇() Da# 下，包括約775 Da或775 Da以下及約75〇 〇3或75() Da以 下，且尤其為約725 Da至約775 Da。對於第^天配方，蛋 白質/肖化率或程度（表示為在如本文中所描述進行分鐘 活體外胰酶消化後之蛋白質MW中值）通常為約75〇 或 750 Da以下，包括約725 Da或725仏以下約7〇〇以或7〇〇 Da以下及約690 Da469〇 Da以下，且尤其為約675 〇&或 675 Da以下至約7〇〇 Da或700 Da以下。 本發明之低熱量嬰兒配方之蛋白質消化率或程度（表示 為在如本文中所描述進行60分鐘活體外胰酶消化後之蛋白 質MW中值）為約10〇〇 D41〇〇〇 Da以下，包括約95〇以或 950 Da以下、約900 〇&或9〇〇 Da以下、約85〇 ^或以 以下、約825 Da或825 Da以下及約810 Da或810 Da以下， 且尤其為約775 Da至約825 Da。 蛋白質消化率或程度亦可表示為在本文中所描述之活體 161200.doc 43- 201233333 外腸胃消化或活體外胰酶消化後Mw大於5〇〇〇 Da之總蛋白 百分比。百分比較小表示消化率較快及消化程度增加。對 於粉末配方，本發明之低熱量嬰兒配方之蛋白質消化率或 程度（表示為在如本文中所描述進行活體外腸胃消化後鮮 大於5000 Da之總蛋白百分比）為約13 5%或13 5%以下包 括約以下、約11〇%或11〇%以下約9 〇〇/〇 或9.0%以下及約6.0%或6〇%以下’且尤其為約5爲至約 13.5。/。。在其中嬰兒配方經殺菌釜滅菌之實施例中，蛋白 質消化率或程度（表示為在如本文中所描述進行活體外腸 胃消化後MW大於5000以之總蛋白百分比）為約8〇%或 U%以下，包括約7.〇%%或7〇%以下約6〇%或6〇%以 下、約5.0%或5.0%以下、約4〇%或4〇%以下及約3 〇%或 3·〇%以下，且進一步包括約2.0°/。至約0.0%。在其中嬰兒配 方經無菌滅菌之實施例中，&白質消化率或程度(表示為 在如本文中所描述進行活體外腸胃消化後MW大於5〇〇〇 之總蛋白百分比）為約9.0%或9.0%以下，包括約7〇%%或 7.〇%以下、約6·0%或6.〇°/❶以下、約5.0%或5.0%以下、約 3.0%或3.0。/。以下’且進一步包括約2〇%至約5〇%。 蛋白質消化率或程度亦可由在如本文中所描述進行活體 外腸胃消化後存在於嬰兒配方中之不可溶蛋白質的量表 示。用於測定不可溶蛋白質含量之技術闡述於本發明之實 例中。不可溶蛋白質量較小表示消化率較快及消化程度增 加0 本發明之低熱量嬰兒配方之蛋白質消化率或程度（表示 161200.doc 201233333 為在如本文t所描述進行活體外腸胃消化後存在於配方中 之不可溶蛋白質的量）為約15〇mg/L或l5〇mg/L以下，包括 約 110 mg/L或110 mg/L 以下、約 75 mg/L或 75 mg/L以下、 約50 mg/L或50 mg/L以下及約25 mg/L或25 mg/L以下，且 尤其為約20 mg/L至約11〇 mg/L。 如本文中所論述，加工嬰兒配方且尤其在高溫下處理乳 產品可增加胺基酸與糖之反應，稱為梅納反應。該等反應 藉由限制蛋白分解酶之可接近性來降低胺基酸之生物可用 性。現已發現與全熱量配方相比，本發明之低熱量嬰兒配 方中梅納反應進行程度較低。此可由測定消化後嬰兒配方 t梅納反應標記物含量說明。明確言之，已發現在如本文 中所描述進行活體外腸胃消化後’本發明之低熱量嬰兒配 方之梅納反應標記物糠胺酸之含量低於全熱量配方。 因此，在一個態樣中，本發明提供嬰兒配方，其在如本 文中所描述進行活體外腸胃消化後包含約2.5或2·5以下， 包括約1.5或1.5以下，約1.〇或ι·〇以下及約〇_9〇或〇_9〇以下 且尤其為約0.7至約1. 〇之量（毫克/丨〇 〇公克產品）的梅納反應 標記物糠胺酸。 製備方法 可由任何已知或其他有效用於製備所選產品固體或液體 形式之製備技術製備本發明之嬰兒配方。已知多種該等技 術用於任何既定產品形式（諸如營養液體或粉末）且可由一 般熟習此項技術者容易地應用於本文中所描述之嬰兒配 方。 161200.doc •45· 201233333 因此本發明之嬰兒配方可由多種已知或其他有效調配或 製備方法中之心種製備。舉例而言，在-種合適製備方 法中，製備至少兩種獨立漿料，隨後將其摻合在一起，進 行...、處理，標準化且最終經滅菌以形成殺菌爸滅菌嬰兒配 方或經無菌處理且填充以形成無菌滅菌嬰兒配方。或者， 漿料可摻合在一起，經熱處理，標準化，第二次熱處理， 蒸發以移除水且噴霧乾燥以形成粉末嬰兒配方。 所形成漿料可包括碳水化合物-礦物質（CH〇_MIN)漿料 及油包蛋白質（protein_in_oil/PIO)漿料。最初’藉由使所 選碳水化合物（例如乳糖、半乳寡醣等）在攪拌下溶解於熱 水中’接著添加礦物質（例如檸檬酸鉀、氣化鎂、氯化 卸氣化鈉、氯化膽驗等）來形成CHO-ΜΙΝ。所得CHOPIN 毁料 保持在 持續加 熱及適 度攪拌 下直至 其隨後 與其他 製備之漿料摻合在一起。 藉由加熱及混合油（例如高油酸紅花子油、大豆油、椰 子油、單甘油酸酯等）及乳化劑（例如大豆卵磷脂），且接著 在持續加熱及授拌下添加油溶性維生素、混合類胡蘿萄 素、蛋白質（例如乳蛋白濃縮物、乳蛋白水解產物等）、角 又菜穋（若存在）、碳酸辦或填酸三約（若存在）以及Ar a油 及DHA油（在一些實施例中）來形成PI〇漿料。所得ρι〇漿料 保持在持續加熱及適度搜拌下直至其隨後與其他製備之聚 料摻合在一起》 加熱水且接著在充分攪拌下與CHO-MIN漿料、脫脂乳 (若存在）及PIO漿料合併。調節所得摻合物之pH值至6.6- 161200.doc -46- 201233333 7·〇 ’且摻合物保持在適度加熱攪拌下。在一些實施例 中’在此階段下添加ARA油及DHA油。 接著組合物經高溫短時（HTST)加工，其間組合物經熱處 理，乳化及均質化，且接著冷卻。添加水溶性維生素及抗 壞血酸，必要時調節pH值至所需範圍，添加香料（若存在） 且添加水以獲得所需總固體含量。對於無菌滅菌嬰兒配 方’乳液經無菌處理器接受第二次熱處理，冷卻且接著無 菌封裝入合適容器中。對於殺菌釜滅菌嬰兒配方，乳液封 裝入合適谷器中且最終滅菌。在一些實施例中，乳液可視 情況進一步經稀釋，熱處理，且封裝以形成所需即食型或 濃縮液體，或可經熱處理且接著處理且封裝為可復原粉末 (例如喷霧乾燥、乾燥混合、聚結）。 可藉由適用於製備及調配營養粉末之任何已知或其他有 效技術集纟製備噴霧乾燥粉末嬰兒配方或乾燥混合粉末嬰 兒配方。舉例而言’當粉末嬰兒配方為喷霧乾燥營養粉末 時’噴霧乾燥步驟可類似地包括任何已知或以纟他方式適 用於製備營養时之噴霧乾燥技術。已知多種;?；同噴霧乾 燥方法及技術用於營養學領域中，其均適用於製備本文中 之喷霧乾燥粉末嬰兒配方。在乾燥後，成品粉末 合適容器中。 使用方法 本發明之低熱量嬰兒配方可經口投與嬰兒，包括足月 兒、早產兒及’或新生兒。低熱量嬰兒配方可投與早產 兒及/或新生兒作為嬰兒營養源及/或可用於解決 161200.doc -47- 201233333 一或多種本文中所論述之疾病或病狀，或可用於提供一或 .多種本文巾所描述之效益1群組巾之任—者可能實際羅 患疾病或病狀，或可能具有罹患疾病或病狀之風險（歸因 於家族史，等），可對疾病或病狀敏感，或可能需要治療/ 控制/減輕某-疾病或病狀。將通常以適用於嬰兒年齡之 攝取量每日投與嬰兒配方^因此 因為本文_揭示之—些 方法實施例係關於嬰兒之某些子群或子類(例如需要治療 或控制錢或病狀之嬰兒）且通常並錢關於標準嬰兒群 體’因此並非所有嬰兒均可自本文中揭示之所有方法實施 例獲益。 舉例而言’本發明之方法可包括以本文中所描述之平均 攝取量投與嬰兒-或多種本發明之低熱量配方。在一些實 施例中，在生命最減週_提供新生兒遞增之配方量。 該等量最通常在生命之約第一天期間在平均至多約1〇〇毫 升/天範@内，在三個月新生兒飯養期之其餘時間期間為 平均至多約200至約毫升/天，包括約細至約繼毫升/ 天且亦包括約250至約500毫升/天。然而應理解，該等量 可視特定新生兒及其在生命最初&週或數月期間的獨特營 養需要以及所投與嬰兒配方之衫營養物及熱量密度而顯 著不同。 在些實施例中，本發明之方法可針對生命最初數週或 數月期間(較佳為生命之至少第一週期間，更佳為生命之 至少最初兩週期間且包括生命之至多約3個月）之新生兒。 此後，嬰兒可轉為食用習知嬰兒配方（單獨或與人乳組 161200.doc 48- 201233333 合）。 本文中所描述之方法可包含投與嬰兒兩種或兩種以上不 同嬰兒配方。舉例而言’可在出生後頭兩天投與嬰兒低熱 量第1-2天嬰兒配方且接著可在出生後第3_9天投與低熱量 第3-9天嬰兒配方。可視情況在出生後第9天過後投與第3_9 天嬰兒配方，或可在出生後第10天開始投與較高熱量配方 (包括全熱量配方）。 除非另有說明，否則本文中所描述之方法中所用嬰兒配 方為營養配方且可呈任何產品形式，包括即食型液體、濃 縮液體、復原粉末及其類似物。在嬰兒配方呈粉末形式之 實施例中，該方法可進一步包含用水性媒劑（最通常為水 或人乳）復原粉末，以形成所需熱量密度，接著經口或經 腸餵養嬰兒。用足量水或其他合適流體（諸如人乳）復原粉 末配方，以產生所需熱量密度及適用於餵養一名嬰兒之所 需飯食量。亦可在使用之前經加壓滅菌殺菌釜滅菌或無菌 滅菌手段對嬰兒配方進行滅菌。 下文更詳細地描述其他實施例。 營養 在一個態樣中，本發明係關於提供嬰兒營養之方法。該 方法包含投與嬰兒任一或多種本發明之低熱量、低微量營 養素嬰兒配方。該等方法可包括每日投與嬰兒配方，包括 以如上文所描述之每日攝取量投與。在一些實施例中，嬰 兒為新生兒。 如上所述，本發明之任何低熱量、低微量營養素嬰兒配 161200.doc •49- 201233333 方均可用於此方法。明喊言之’低微量營養素嬰兒配方包 含微量營養素及至少一種選自由蛋白f、碳水化合物、脂 肪及其組合組成之群的常量營養素。在一個實施例中，低 微量營養素嬰兒配方之能量含量為約200 kcal/L至小於6〇〇 kcal/L，其中至少65%微量營養素以習知相應微量營養素 量之約30%至約80%之量包括於嬰兒配方中（以單位體積 計）。在另一實施例中，低微量營養素嬰兒配方之能量含 量為約200 kcal/L至約360 kcal/L，其中至少45。/。微量營養 素以習知相應微量營養素量之約3〇%至約65%之量包括於 嬰兒配方中（以單位體積計）。在另一實施例中，低微量營 養素嬰兒配方之能量含量為約36〇 kcai/L至小於6〇〇 kcal/L，其中至少3〇〇/0微量營養素以習知相應微量營養素 量之約55%至約80%之量包括於嬰兒配方中（以單位體積 計）。低熱量嬰兒配方可為第1-2天配方及/或第3_9天配 方。 該方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之低熱 量嬰兒配方（具有高或低微量營養素含量）（例如第1_2天配 方）’且接著在出生後第3天至第9天投與能量含量為約360 kcal/L至小於600 kcai/L之低熱量嬰兒配方（具有高或低微 量營養素含量）（例如第3-9天配方）。可視情況在出生後第9 天過後投與第3-9天嬰兒配方，或可在出生後第1〇天開始 投與較高熱量配方（包括全熱量配方）。 I6I200.doc 201233333 緩衝能力 已發現嬰兒配方之缓衝能力與配方之能量含量有關。明 確言之，已發現嬰兒配方之緩衝能力隨能量含量降低而降 低。因此本發明之低熱量嬰兒配方與全熱量嬰兒配方相比 有利地具有改良（亦即較低）之緩衝能力，且在一些實施例 中’其緩衝能力低於人類母乳。因此本發明之低熱量嬰兒 配方可用於增加嬰兒且尤其新生兒之胃液酸度及調節嬰兒 之腸胃菌叢生長，包括控制（例如降低）嬰兒腸胃道中病原 微生物生長、促進嬰兒腸胃道中有益微生物生長及增加使 經口攝取之病原體失活的有效性。 不希望受任何特定理論約束’咸信與全熱量配方傲養嬰 兒相比，母乳飯養嬰兒之腸胃道中pH值酸性更強，從而有 助於經口攝取之病原體之失活且提供更適宜天然存在之有 益腸胃菌叢生長之環境。咸信此至少部分地歸因於人類母 乳之低緩衝能力。因為本發明之低熱量嬰兒配方之緩衝能 力與人類母乳相當或低於人類母乳，因此本文中揭示之低 熱量嬰兒配方餵養之嬰兒之胃液酸度將更接近地類似於母 乳餵養嬰兒中可見者。 因此，在一個態樣中，本發明係關於使嬰兒之胃液酸度 增加（例如藉由降低胃液pH值）至與母乳餵養嬰兒約相同程 度之方法。該方法包含鑑別胃液酸度降低之嬰兒且對該嬰 兒投與任何本發明之低熱量嬰兒配方。嬰兒較佳為新生 兒。 術浯「胃液酸度」係指胃中酸性程度且可使用pH值量 161200.doc •51 · 201233333 測。舉例而言，胃液酸度隨胃内含物之pH值降低而增加。 如本文中所用’術語「胃液酸度降低」意謂嬰兒之胃液酸 度低於母乳傲養嬰兒中通常可見之胃液酸度。胃液酸度降 低之嬰兒可鑑別為腸道中病原菌群落形成速率降低或較 低。在投與本發明之低熱量嬰兒配方後，嬰兒之胃液酸度 增加至通常可見於母乳餵養嬰兒中之程度。 如上所述，任何本發明之低熱量嬰兒配方均可用於此方 法。低熱量嬰兒配方可具有低微量營養素含量，或在一些 實施例中，可具有高微量營養素含量，且可為第l_2天配 方或第3-9天配方。在一個實施例中，嬰兒配方之能量含 量為約 200 kcal/L至約 500 kcal/L。 該方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之第1-2 天配方，且接著在出生後第3至9天投與能量含量為約36〇 kcal/L至小於600 kcal/L之第3-9天配方。可視情況在出生 後第9天過後投與第3_9天嬰兒配方，或可在出生後第丨❽天 開始投與較高熱量配方（包括全熱量配方）。投與嬰兒之配 方將通常以如上述攝取量每日投與。 在另一態樣中’本發明係關於提高嬰兒之胃液酸度之方 法，其包含投與嬰兒任何本發明之低微量營養素嬰兒配 方毛"兒較佳為新生兒。低微量營養素嬰兒配方包含微量 營養素及至少一種選自由蛋白質、碳水化合物、脂肪及其 組合組成之群的常量營養素。在一個實施例中，低微量營 161200.doc •52· 201233333 養素嬰兒配方之能量含量為約200 kcal/L至小於6〇〇 kcal/L，其中至少65%微量營養素以習知相應微量營養素 量之約3 0%至約80°/〇之量包括於嬰兒配方中（以單位體積 計）。在另一實施例中，低微量營養素嬰兒配方之能量含 量為約200 kcal/L至約360 kcal/L，其中至少45%微量營養 素以習知相應微量營養素量之約30%至約65%之量包括於 嬰兒配方中（以單位體積計）。在另一實施例中，低微量營 養素嬰兒配方之能量含量為約36〇 kcal/L至小於600 kcal/L，其中至少30%微量營養素以習知相應微量營養素 量之約5 5%至約80%之量包括於嬰兒配方中（以單位體積 計）。低熱量嬰兒配方可為第1_2天配方及/或第3_9天配 方。 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而言，在一個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之低 熱量嬰兒配方（具有高或低微量營養素含量）(例如第1-2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 360 kcal/L至小於600 kcal/L之低熱量嬰兒配方（具有高或低 微量營養素含量)(例如第3_9天配方）。可視情況在出生後 第9天過後投與第3_9天嬰兒配方，或可在出生後第天開 始投與較高熱量配方(包括全熱量配方)。在低熱量嬰兒配 方具有低微量營養素含量之實施例中，配方中所包括之微 量s養素里可為任一上述含量。投與嬰兒之配方將通常以 如上述攝取量每日投與。 161200.doc •53- 201233333 在另一實施例中，本發明係關於調節嬰兒中有益腸胃菌 叢生長之方法。該方法包含鑑別腸胃菌叢生長不平衡之嬰 兒且對該嬰兒投與任何本發明之低熱量嬰兒配方。嬰兒較 佳為新生兒。 為達成本發明目的，可藉由促進有益於GI健康之微生物 生長及/或控制病原微生物生長來調節腸胃菌叢生長。可 藉由制止、抑制、殺滅、失活、破壞或以其他方式妨礙病 原微生物生長使得該等微生物之生長速率減緩或停止來控 制病原微生物生長。GI菌叢生長不平衡之嬰兒包括嬰兒腸 胃道中一或多種病原微生物含量高於通常可見於母乳餵養 4c兒中之含量及/或嬰兒腸胃道中一或多種有益微生物含 量低於通常可見於母乳餵養嬰兒中之含量的嬰兒。該等嬰 兒可由腸道中病原菌群落形成速率較低鑑別。在投與本發 明之低熱量嬰兒配方後，嬰兒之胃液酸度增加至與通常可 見於母乳餵養嬰兒中類似之程度，從而產生促進有益微生 物生長及控制病原微生物生長之GI環境。 如上所述’任何本發明之低熱量嬰兒配方均可用於此方 法。低熱量嬰兒配方可具有低微量營養素含量，或在一些 實施例中’可具有高微量營養素含量，且可為第1 _2天配 方或第3-9天配方。在一個實施例中，嬰兒配方之能量含 量為約200 kcal/L配方至約500 kcal/L配方。 s玄方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之第1_2 161200.doc •54· 201233333 天配方，且接著在出生後第3至9天投與能量含量為約36〇 kcal/L至小於600 kcal/L之第3_9天配方。可視情況在出生 後第9天過後投與第3_9天嬰兒配方，或可在出生後第1〇天 開始投與較高熱量配方（包括全熱量配方）。投與嬰兒之配 方將通常以如上述攝取量每日投與。 在另一態樣中，本發明係關於調節嬰兒之腸胃菌叢生長 之方法，其包含投與嬰兒任何本發明之低微量營養素嬰兒 配方。嬰兒較佳為新生兒。低微量營養素嬰兒配方可為任 一上述配方》 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而言，在一個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之低 熱S嬰兒配方（具有高或低微量營養素含量）(例如第丨_2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 360 kcal/L至小於600 kcai/L之低熱量嬰兒配方（具有高或低 微量s養素3里）（例如第3-9天配方）。可視情況在出生後 第9天過後投與第3_9天嬰兒配方，或可在出生後第1〇天開 始投與較高熱量配方（包括全熱量配方）。在低熱量嬰兒配 方具有低微量營養素含量之實施例中，配方中所包括之微 量營養素量可為任一上述含量。投與嬰兒之配方將通常以 如上述攝取量每日投與。 有益微生物係指保持腸胃豸之微生物生態學且展示生理 學、免疫調節及/或抗微生物作用，使得發現其存在可預 防及治療GI疾病及/或病症之微生物。有益微生物之非限 161200.doc -55- 201233333 制性實例包括以下微生物中之任一或多者：乳桿菌屬 (genus ，包括嗜酸乳桿菌（I. aczWop/n'/w·?)、 食殿粉乳桿菌（Ζ· amy/ovorw·?)、短乳桿菌（Z. AreW·?)、保加 利亞乳桿菌（Z. h/garicw·?)、乾路乳桿菌乾酷·亞種（Z. casez· 5/?/7. Caiez·)、乾酷乳桿菌鼠李糖亞種（L. ciiiez· ίρρ. 及/zawwoswi)、捲曲乳桿菌（Ζ«· crh/yaiwi)、德氏乳桿菌乳亞 種（L. i/e/ftrwecA:iz· w/?. Lac"··?)、醋酵乳桿菌（L. /erme«iM/n)、 瑞士 乳桿菌（!《· Zie/vaiicws)、約氏乳桿菌（Ζ<· yo/mscm/i·)、副 乾酷·乳桿菌（[· pwacaseO、戊糖乳桿菌（L. pewiosws)、胚 芽乳桿菌（Z. /?/<2«iarwm)、洛德乳桿菌（Z. rei/ierz·)及清酒乳 桿菌（Z· •sak);雙叉桿菌屬（genus 5(/ii/o6atcieriwm)，包括 動物雙叉桿菌（5. 、雙歧雙叉桿菌（5. 、 短型雙叉桿菌（Β· fcreve)、嬰兒雙又桿菌（5. /«/<3«沿）及龍 根雙叉桿菌（凡longum) \小球菌屬（genus Pe山·ococew·?) ’ 包括乳酸小球菌（P. aeii/z7acnW);丙酸桿菌屬（genus. Propionibacterium)，包括丙酸丙酸桿菌（R acidipropionici)、 費氏丙酸桿菌（户./reMi^”rez‘c/n7)、詹氏丙酸桿菌（·Ρ. 及塞氏丙酸桿菌（P. ;及鍵球菌屬（genus •Sirepiococcws)，包括乳酷鍵球菌（51· crewor/i)、乳鍵球菌 (<S. /acn'i)及嗜熱鏈球菌（S. ;及其組合。 可由本文中揭示之方法控制生長之病原微生物之非限制 性實例包括以下病原微生物中之任一或多者：細菌，諸如 梭菌属（genus C/oWrWww) ’包括難養芽胞梭菌（C. difficile) ·，大陽得 Wi [Escherichia coli/E. colV) ’，孤儀凰 161200.doc -56- 201233333 π.);沙門氏菌屬（以/w〇加ζ/α w );志贺桿菌屬 (*S/ny//a W.);曲桿菌屬（Cimp/〇^hcier 印）；產氣單胞 菌 M(Aer〇m〇nas sp·).，葡萄球菌魇（Staphyl〇c〇ccus sp) •’ 假單胞菌屬（PseMc/owonw印）；及寄生物，諸如梨形鞭毛 蟲屬（Gkdk叹.）；及隱胞子蟲屬（Crw?i〇w⑻·印）； 及其組合。 蛋白質消化及水解 已發現嬰兒配方中蛋白質之消化率及程度與配方之能量 含量有關。明確言之’已發現嬰兒配方中之蛋白質之消化 率隨配方之能量含量降低而增加。因此本發明之低熱量嬰 兒配方與全熱量嬰兒配方相比有利地具有改良（例如更快） 之消化率。因此本發明之低熱量嬰兒配方可用於改良嬰兒 且尤其新生兒之配方耐受性、蛋白質消化及營養物(且尤 其蛋白質）吸收。 因此’在-個態樣中，本發明係關於改良嬰兒之蛋白質 消化之方法。該方法包含鐘別經歷蛋白質消化不全之嬰兒 且對該嬰兒投與任何本發明之低熱量嬰兒时。嬰兒較佳 為新生兒。 如本文中所用，術語「改良蛋白質消化」包括提高存在 嬰兒配方中蛋白質t消化（或水解）率及/或增加嬰兒配方中 蛋白質與消化酶接觸時的消化程度。此蛋白質消化改良可 使用任何本文中所描述之量度敎，包括（例如）消化後蛋 白質中值重量、消化後分子量大於5_道爾頓之佔總蛋白 質百分比及/或消化後存在於配方中之不可溶蛋白質的 161200.doc •57· 201233333 量。 如本文中所用，術語「蛋白質消化不全」意謂存在於嬰 兒食用之營養產品中的蛋白質實際消化之量低於母乳餵養 嬰兒通常消化之蛋白質的量。經歷蛋白質消化不全之嬰兒 可能展示配方不耐受性跡象且可因此使用任何本文中所描 述之配方不耐受性症狀鑑別《亦可由腹瀉、軟便、放屁 及/或氣脹鑑別經歷蛋白質消化不全之嬰兒。在投與本發 明之低熱量嬰兒配方後’蛋白質消化率及程度得到改良。 如上所述，任何本發明之低熱量嬰兒配方均可用於此方 法。低熱量嬰兒配方可具有低微量營養素含量，或在一些 實施例中’可具有高微量營養素含量，且可為第1_2天配 方及/或第3-9天配方。在一個實施例中，嬰兒配方之能量 含量為約200 kcal/L配方至小於600 kcal/L配方。 該方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之第1-2 天配方，且接著在出生後第3至9天投與能量含量為約360 kcal/L至小於600 kcal/L之第3-9天配方。可視情況在出生 後第9天過後投與第3-9天配方，或可在出生後第10天開始 投與較高熱量配方（包括全熱量配方）。投與嬰兒之配方將 通常以如上述攝取量每日投與。 在另一態樣中’本發明係關於改良嬰兒之蛋白質消化之 方法’其包含投與嬰兒任何本發明之低微量營養素嬰兒配 方°嬰兒較佳為新生兒。低微量營養素嬰兒配方包含微量 16120〇.<ΐ()ς -58- 201233333 S養素及至乂種選自由蛋白質、碳水化合物、脂肪及其 組合組成之群的常量營養素。在一個實施例中，低微量營 養素嬰兒配方之能量含量為約200 kcal/L至小於600 kcal/L其中至少65%微量營養素以習知相應微量營養素 量之約3 G %至約嶋之量包括於嬰兒配方中（以單位體積 計）。在另一實施例中，低微量營養素嬰兒配方之能量含 里為’’勺200 kcal/L至約360 kcal/L，其中至少45%微量營養 素以習知相應微量營養素量之約3〇%至約65%之量包括於 嬰兒配方中（以單位體積計）。在另一實施例中，低微量營 養素嬰兒配方之能量含量為約36〇 kcal/L至小於600 kcal/L，其中至少30〇/〇微量營養素以習知相應微量營養素 量之約55%至約80%之量包括於嬰兒配方中（以單位體積 計）。低熱量嬰兒配方可為第1-2天配方及/或第3_9天配 方。 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而言，在一個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約2〇〇 kcal/L至約360 kcal/L之低 熱量嬰兒配方（具有高或低微量營養素含量）（例如第1_2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 360 kcal/L至小於600 kcal/L之低熱量嬰兒配方（具有高或低 微量營養素含量）（例如第3-9天配方）。可視情況在出生後 第9天過後投與第3-9天配方，或可在出生後第1 〇天開始投 與較高熱量配方（包括全熱量配方）。在低熱量嬰兒配方具 有低微量營養素含量之實施例中，配方中所包括之微量營 161200.doc -59- 201233333 養素量可為任一上述含量。投與嬰兒之配方將通常以如上 述攝取量每日投與。 在另一實施例中’本發明係關於改良嬰兒之蛋白質吸收 之方法。該方法包含鑑別經歷蛋白質吸收不全之嬰兒；及 對該嬰兒投與任何本發明之低熱量嬰兒配方。可使用本文 中所描述用於鑑別經歷蛋白質消化不全之嬰兒之準則中之 任一者鑑別經歷蛋白質吸收不全之嬰兒。 如上所述，任何本發明之低熱量嬰兒配方均可用於此方 法。低熱量嬰兒配方可具有低微量營養素含量，或在一些 實施例中，可具有高微量營養素含量，且可為第1_2天配 方或第3-9天配方。在一個實施例中，嬰兒配方之能量含 量為約200 kcal/L配方至小於600 kcal/L配方。 該方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之第1-2 天配方，且接著在出生後第3至9天投與能量含量為約360 kcal/L至小於600 kcal/L之第3-9天配方。可視情況在出生 後第9天過後投與第3-9天配方，或可在出生後第1 〇天開始 投與較高熱量配方（包括全熱量配方）。投與嬰兒之配方將 通常以如上述攝取量每日投與。 在另一態樣中，本發明係關於改良嬰兒之蛋白質吸收之 方法，其包含投與嬰兒任何本發明之低微量營養素嬰兒配 方。嬰兒較佳為新生兒。低微量營養素嬰兒配方可為任一 上述配方。 161200.doc -60- 201233333 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而言，在一個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之低 熱里嬰兒配方（具有尚或低微量營養素含量）（例如第I·〗天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 3 60 kcal/L至小於600 kcal/L之低熱量嬰兒配方（具有高或低 微量營養素含量）（例如第3_9天配方）。可視情況在出生後 第9天過後投與第3-9天嬰兒配方，或可在出生後第1〇天開 始投與較高熱量配方（包括全熱量配方）。在低熱量嬰兒配 方具有低微量營養素含量之實施例中，配方中所包括之微 量營養素量可為任一上述含量。投與嬰兒之配方將通常以 如上述攝取量每日投與。 耐受性 本發明亦係關於改良嬰兒之嬰兒配方耐受性之方法。嬰 兒配方不耐受性為非免疫性系統相關反應，其可由行為或 糞便或進食型態變化所證實，諸如咳吐或嘔吐增加、排便 次數增加、水狀便較多、黑色糞便及哭鬧增加。嬰兒配方 不耐爻性最通常與腸胃症狀（例如糞便形態、放屁、咳吐） 以及行為特徵（例如配方接受度、哭鬧及喊叫）有關。罹患 配方不耐受性之嬰兒亦可能經歷胃食道逆流。 現意外發現嬰兒對具有低能量含量之嬰兒配方之耐受性 大於全熱量配方。明確言之，已發現與全熱量配方相比， 低熱量嬰兒配方顯示較快蛋白質水解及消化率、在食用後 產生較少梅納反應產物（其無法分解及吸收）且具有較快胃 I61200.doc -61 - 201233333 排空速率。胃排空較快時，可減少胃食道逆流及改良配方 对受性。 因此本發明之低熱量嬰兒配方可用於減少嬰兒放屁及/ 或咳吐發生頻率。本發明之低熱量嬰兒配方與全熱量嬰兒 配方相比亦可用於提高嬰兒之胃排空速率及降低由食用配 方所產生之梅納反應產物量。 低熱量嬰兒配方可投與任何嬰兒（早產兒或足月兒）且尤 其任何可自接受具有低能量含量且亦具有高耐受性之嬰兒 配方獲益之嬰兒。在一些實施例中，對新生兒投與本發明 之低熱量嬰兒配方。 因此，在一個態樣中，本發明亦係關於改良嬰兒之嬰兒 配方耐受性之方法。該方法包含鑑別罹患嬰兒配方不耐受 性之嬰兒及對該嬰兒投與任一或多種本發明之低熱量嬰兒 配方。罹患嬰兒配方不耐受性之嬰兒可包括具有配方不耐 受性之任一或多種症狀之嬰兒。該等症狀包括（但不限於） 糞便或進食型態變化，諸如咳吐或β區吐增加；排便次數增 加；水狀便較多；黑色糞便；哭鬧、喊叫、放屁增加；及 不願食用配方。在投與本發明之低熱量嬰兒配方後，可減 少或消除一些或所有配方不耐受性症狀。 如上所述，任何本發明之低熱量嬰兒配方均可用於此方 法。低熱量嬰兒配方可具有低微量營養素含量，或在一些 實施例中，可具有高微量營養素含量，且可為第12天配 方或第3·9天配方。在—個實施例中，低熱量嬰兒配方之 能量含量為約200至約6〇〇千卡/公升配方。 161200.doc •62· 201233333 該方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之第1-2 天配方，且接著在出生後第3至9天投與能量含量為約36〇 kcal/L至小於600 kcal/L之第3-9天配方。可視情況在出生 後第9天過後投與第3-9天配方，或可在出生後第1〇天開始 投與較咼熱量配方（包括全熱量配方）。投與嬰兒之配方將 通常以如上述攝取量每日投與。 在另一態樣中，本發明係關於改良嬰兒之嬰兒配方耐受 性之方法，其包含投與嬰兒任何本發明之低微量營養素嬰 兒配方。嬰兒較佳為新生兒。低微量營養素嬰兒配方包含 微量營養素及至少一種選自由蛋白質、碳水化合物、脂肪 及其組合組成之群的常量營養素。在一個實施例中，低微 量營養素嬰兒配方之能量含量為約2〇〇 kcal/L至小於6〇〇 kcal/L，其中至少65%微量營養素以習知相應微量營養素 量之約30%至約80。/。之量包括於嬰兒配方中（以單位體積 汁）。在另一實施例中，低微量營養素嬰兒配方之能量含 量為約200 kcal/L至約360 kcal/L，其中至少45%微量營養 素以習知相應微量營養素量之約3〇%至約65%之量包括於 嬰兒配方中（以單位體積計）n實施例中，低微量營 養素嬰兒配方之能量含量為約36〇 kcal/L至小於6〇〇 ^，其中至少Μ%微量營養素以習知相應微量營養素Vcream is the separation speed of the cream. Pfluid is formulated in the "degree P p a r t i c 1 e is the particle probabilities η is the formula viscosity R is the average particle size g is the gravitational acceleration. The stability of liquid infant formula emulsions generally increases with decreasing cream separation speed. It has been found that the low-calorie, low-micronutrient 1st-day bactericidal dad sterilized liquid infant formula of the present invention has a lower emulsification separation rate than the low-calorie, high-micronutrient 1st-day sterilizing liquid sterilized liquid infant formula. Thus, in one aspect, the present invention relates to a low calorie, low micronutrient liquid infant formula that has a low cream separation rate compared to a low calorie, high micronutrient infant formula. The low-calorie, low-micronutrient liquid infant formula is preferably a sterilization dad-sterilized RTF formula, and more preferably a 1st-day sterilization dad-sterilized liquid infant formula. In embodiments in which the low calorie, low micronutrient liquid infant formula is the 1-2 day infant formula, the infant formula may have an emulsification separation rate of typically about 5.0 cm/day or less than 5.0 cm/day, including about 1.0 cm/ The day is about 5.0 cm/day, about 3·cm/day to about 35 cm/day and especially about 3. 2 cm/day. 161200.doc •35· 201233333 Color The low calorie, low micronutrient liquid infant formula of the present invention also advantageously exhibits color improvement as compared to low heat, high micronutrient formulations. Liquid infant formulas contain a variety of nutrients that may interact during formulation, processing, and storage. These interactions can distort the color of the formula to gray, beige or other similar discoloration. These discolorations often cause consumer acceptance of the product to be greatly reduced, and consumers generally prefer bright, white products. One technique that can be used to assess the color characteristics of an infant formula is the Agtron color score. The Aeghen scoring system used herein was measured by a conventional technique using an Agtron 45 spectrophotometer (available from Agtron Inc., Reno, Nevada). Aegis is divided into measurements of the percentage of energy (light) reflected from the surface of each infant formula. The stronger or brighter the color of the surface of the formula is, the higher the score is. These scores range from 〇 (black) to 100 (white). It has been found that the micronutrient content of low calorie liquid infant formulas can affect the formula color. In particular, the low calorie, low micronutrient liquid infant formula of the present invention has a brighter, whiter color (as defined by the Aegean score) compared to the low calorie, high micronutrient formula. This is found in both sterilization and aseptic sterilization - low calorie, low micronutrient liquid formulations. Not only is the _, after just after the deployment, and also after a long period of time (in some cases, at least 9 months after product preparation), the color improvement of the low calorie, low micronutrient liquid infant formula is observed. Therefore, in one aspect, the present invention relates to a low-calorie, low-micro-capacity 161200.doc-36 · 201233333 nutrient w-day liquid infant formula, which is formulated to be at least about after the blending (within ... days) 45, comprising from about 45 to about 6 〇 and from about 47 to about 55. The formulation is preferably a sterilized dad sterilized RTF formulation. In other embodiments, the formula is divided into at least about 4 〇, including about 4 〇 to about 50, for two months after the formulation; the AI JI is divided into at least about 37 after the blending, including about Up to about 50; Aegis is divided into at least about 37, including about 37 to about 50, for six months after blending; and the Eiger is divided into at least about 35, including about 35 to about nine months after the blending. 45. In another aspect, the present invention relates to a low calorie, low micronutrient 3-9 day liquid sterilizing infant sterilized infant formula, wherein the formulated Aige Zhuang is divided into at least about 42, including about 42 to about 55 and about 45 to about 52. In other embodiments, the formula is divided into at least about 4 〇, including about 40 to about 50, for three months after the formulation; and the Aige, which is six months after the blending, is divided into at least about 4 〇, including About 40 to about 50. In another aspect, the present invention relates to a low-calorie, low-micronutrient 3-9 day liquid aseptically sterilized infant formula, which is formulated to have an Aegis score of at least about 58' including from about 58 to about 65 and about 60. To about 62. In other embodiments, the formulation is divided into at least about 55, including from about 55 to about 62, for two months after formulation; the Aegean score of at least about 55 after the formulation is divided into at least about 55, including about 55 to Approximately 60; and nine months after the blending, the Eiger is divided into at least about 52, including about 52 to about 55. Buffering Capacity The low calorie infant formula of the present invention (having high or low micronutrient content) also advantageously exhibits improved cushioning capacity as compared to a full calorie formulation. 161200.doc .37· 201233333 The human breast milk contains certain factors that promote the beneficial intestinal bacteria community (clearly speaking, the factor of Bifidobacterium development, Bifidobacterium can prevent the proliferation of pathogenic microorganisms. The growth of Bifidobacterium in the intestinal tract of the baby It is promoted by the physical and chemical properties of human breast milk (especially its high lactose content, which is the quality of the bifurcated bacteria), its low protein content and its low buffering capacity. In addition, the low buffering capacity of human milk can make the baby's stomach The natural acidity in the GI is more effective in inactivating pathogens that are orally ingested. In some cases, infant formulas may have relatively high buffering capacity, which may not be entirely beneficial for the growth of Bifidobacterium and may potentially affect The natural acidity of the baby's gastrointestinal tract. Therefore, some formula-raised babies may experience more gastrointestinal infections than breast-fed babies. It is found that the buffering capacity of infant formula is related to the energy content of the formula. It has been found that the buffering capacity of the infant formula decreases as the energy content decreases. Therefore, the low calorie infant formula of the present invention and the full calorie infant The formulation advantageously has an improved (i.e., lower) buffering capacity, and in some embodiments 'the buffering capacity is lower than human milk. Thus, the low calorie infant formula of the present invention can be used to regulate infants and especially newborns. The acidity of the gastric juice reduces the growth of pathogenic microorganisms in the gastrointestinal tract of the infant, promotes the growth of beneficial microorganisms such as Bifidobacterium, and increases the effectiveness of inactivation of pathogens that are orally ingested. Buffering capacity generally refers to the ability of a liquid to resist changes in pH. There are many measures of the buffering capacity of the infant formula of the present invention. For example, the buffering capacity of the infant formula can be expressed as hydrogen after the addition of hydrochloric acid (HC1) to the infant formula (or the reconstituted formula to the powder infant formula embodiment). The increase in ion Han ([H+]). Specifically, the buffer capacity is expressed as the increase in [H+] after adding 5mm〇丨hci to the 1〇〇mL formula 161200.doc • 38 · 201233333, or Add 5.5 mm to the 丨(10) claw ^ yourself <)1 The increase in [H+] after HC1 (or 2,75 leg 〇1 HC1 is added to the formulation). The buffering capacity of the low calorie infant formula of the present invention (expressed as [H+] after adding 5 mmol Ha to the 1 〇〇 formulation) can be at least about 2 mM, including at least about 5.0 mM, at least about 7 mM, At least about 1 〇 〇 、, at least about 13.0 and at least about 17. mM, and/or from about 2 〇 mM to about 25 〇 mM, including from about 5 〇 mM to about 21 〇 mM and about i 〇〇 to about 21 〇 mM. The infant formula can be a reconstituted powder formulation (sterilization or sterile sterilization) and can be formulated on Days 1 - 2 or Day 3. In one embodiment, the low calorie infant formula is a 3-9 day formulation and its buffering capacity (expressed as [H+] after adding 5 mmol of HC1 to the 丨〇() m]L formulation is at least about 2.0 mM And comprising at least about 5.0 mM, at least about 7 〇 and at least about 9 ,, and/or from about 2.0 mM to about 13.0 mM, including from about 8 〇 mM to about n 〇 mM. In another embodiment, the low calorie infant formula is the 丨_2 day formula and its buffering capacity (expressed as [H+] after adding 5 mm 〇1 Ηα to the 100 mL formulation) is to >, about 8.0 mM, Including at least about 1 mM, at least about 13 〇, at least about 17·〇 mM, and at least about 20.0 mM, and/or about 8 〇 mM to about 25 〇 mM, including about 8. 〇 mM to about 21 〇 mM, Approximately 13 pawls up to about 2 mM and about 17.0 mM to about 20.0 mM. Alternatively, the buffering capacity of the infant formula can be expressed as a decrease in the pH of the formula added to the infant formula (or to the reconstituted formula of the powder infant formula embodiment). Specifically, buffering capacity can be expressed as the addition of 5.5〇mmol HC1 to a 1〇〇mL formulation (or 2 75 facets 1 HC1 to a 5〇mL formulation) 161200.doc -39- 201233333 . Thus, 'in one embodiment, the low calorie infant formula of the present invention is a powdered infant formula and its cushioning capacity after reconstitution (expressed as a decrease in the pH of the formulation after adding 5.50 mmol of HC1 to the 1 mL recovery formula) It is at least about 4.20, including at least about 5 冬 and at least about 4 〇. In another embodiment wherein the low calorie infant formula is a sterilized autoclaved RTF formulation, the buffering capacity (represented as a decrease in pH of the formulation after adding 2.75 mmol of HCl to the 50 mL formulation) is at least about 4.20, including at least about 4.30. » In yet another embodiment wherein the low calorie infant formula is a sterile sterilized RTF formulation, the buffering capacity (represented as a decrease in pH of the formulation after adding 5.50 mmol of HCl to the 100 mL formulation) is at least about 4.60, including at least about 4.70 . Another measure of buffer capacity is the buffer strength. Unless otherwise stated, the buffer strength of the infant formula of the present invention can be expressed as required to reduce the pH of the 50 mL formulation (or the reconstituted formulation of the powdered infant formula embodiment) from the initial pH (eg, 6.0) to pH 3.0. The volume of 0.1 M HC1. As used herein, the term "low buffer strength" means a buffer strength of about 18 mL or less. The buffer strength (when indicated) is also expressed herein as the millimolar amount of HC1 required to reduce the pH of the 100 mL formulation from 6.0 to 3.0 and the pH of the 50 mL formulation from 6.0 to 3.0. The amount of milligrams of HC1. The buffer strength of the low calorie infant formula of the present invention (expressed as the pH of the 0.1 mL HC1 required to reduce the pH of the 50 mL formulation (or the reconstituted formula of the powdered infant formula embodiment) from the initial pH to pH 3.0) It is about 18 mL or less, including about 14 mL or less, and/or includes from about 9 mL to about 18 mL, including from about 10 mL to about 14 mL and from about 14 mL to about 18 mL. In an embodiment, the low calorie infant formula is a 3rd-9th formulation and has a buffer strength of about 18 mL or less> including from about 14 mL to about 18 mL and from about 16 mL to about 17 mL. In another embodiment, the low calorie infant formula is a 1-2 day formulation and has a buffer strength of about 14 mL or less, including from about 9 mL to about 14 mL and from about 10 mL to about 11 mL. The buffer strength of human milk is usually in the range of 9 mL to 18 mL. The low calorie infant formula of the present invention advantageously has a buffer strength comparable to or lower than that of human milk. Protein Hydrolysis and Digestion The low-calorie infant formula of the present invention (having high or low micronutrient content) also advantageously exhibits faster protein hydrolysis and digestibility compared to the full calorie formulation. Two factors that determine the nutritional quality of the food protein are digestion. Rate and bioavailability. Generally, the infant formula has a higher protein content than the protein content found in breast milk. Infant formulas are usually prepared with higher protein content to address the problem of hypothetical protein digestibility. In addition, in some instances, the method used during infant formula preparation may have a potential nutritional effect on the moonlight, such as reducing the solubility and/or digestibility of the protein in the formulation. For example, in some cases, some prolonged heat treatments for preparing concentrated liquids and ready-to-eat infant formulas may potentially reduce protein digestibility. Due to exposure to heat, protein denaturation or aggregation may in some cases alter its digestibility. Treatment of dairy products at elevated temperatures may also involve the reaction of amino acids with sugars, known as the MaiiiaU reaction. In some cases, such reactions may reduce the bioavailability of the amino acid by limiting the proximity of the proteolytic enzyme. Therefore, some formula-fed 161200.doc 201233333 infants may experience some nutrient (and especially protein) insufficiency. Therefore, infant formulas with improved protein digestion will be particularly beneficial for newborns with known levels of digestive enzymes (such as pepsin and entero-trypsin) that are lower than older infants and adults. It has been found that the degree of protein digestion in infant formula (which may be used interchangeably herein with the term "hydrolysis") (which may be used interchangeably herein with the term "rate") is related to the energy content of the formulation. Specifically, it has been found that the digestibility of the protein present in the infant formula increases as the energy content of the formula decreases. "The low calorie infant formula of the present invention advantageously has improved (e.g., faster) protein compared to the full calorie infant formula. Digestibility. This improves the infant's tolerance to infant formula and improves the absorption of nutrients (and especially protein). There are many types of measures for expressing the rate or extent of protein digestion. For example, the digestibility or degree of protein in the infant formula of the present invention is based on the use of lunar protein and trypsin (amylase/protease/lipase) for in vitro gastrointestinal/scholarization or in vitro trypsin digestion of protein. The median molecular weight (Mw) is expressed. A decrease in the median MW of the protein indicates a faster digestibility and an increased degree of digestion. The procedure for such digestion is illustrated in the examples. In some embodiments, the protein digestibility or extent of the low calorie infant formula of the present invention (expressed as the median MW of protein after in vitro gastrointestinal digestion as described herein) is about 950 Daltons (Da) or 95 〇 Dalton below, including below 925 Da or 925 Da, about 85 〇〇 & or 85 〇 Da, below 800 Da or 800 Da and below about 790 Da479 () Da. For the 3rd-9th day formulation of the present invention, the protein digestibility or extent (expressed as the median protein Mw after in vitro gastrointestinal digestion as described herein at 161200.doc -42 - 201233333) is typically about 700 Da to About 950 Da. For the day u formulation, the protein digestibility or extent (not shown as the median MW of the protein after in vitro gastrointestinal digestion as described herein) is typically below about 825 !^ or 825 Da, including about 800 Da or 800 Below Da, about 780 D478〇Da, about 75〇Da or 750 Da or less and about 720!^ or 72〇Da or less. The protein digestibility or degree of the second day formulation is typically from about 7 〇〇 Da to about 8 〇〇 Da. For the Days 3-9 formulation, the protein digestibility or extent of the low calorie infant formula of the present invention (expressed as the median value of the protein elbow after in vitro trypsinization as described herein) was about 8 〇〇〇& or 8〇() Da#, including below about 775 Da or 775 Da and below about 75〇〇3 or 75() Da, and especially from about 725 Da to about 775 Da. For the day of the formula, the protein/shake rate or degree (expressed as the median MW protein after minute in vitro trypsinization as described herein) is typically about 75 〇 or 750 Da, including about 725 Da. Or below 725 约, about 7 〇〇 or 7 〇〇 Da and about 690 Da 469 〇 Da, and especially about 675 〇 & or 675 Da or less to about 7 〇〇 Da or below 700 Da. The protein digestibility or extent of the low calorie infant formula of the present invention (expressed as the median MW of protein after 60 minutes of in vitro trypsinization as described herein) is below about 10 〇〇 D41 〇〇〇 Da, including About 95 〇 or 950 Da or less, about 900 〇 & or 9 〇〇 Da, about 85 〇 ^ or less, about 825 Da or 825 Da or less and about 810 Da or 810 Da or less, and especially about 775 Da to about 825 Da. The protein digestibility or extent can also be expressed as the percentage of total protein with a Mw greater than 5 〇〇〇 Da after parenteral digestion or in vitro trypsin digestion in the living body described herein. 161200.doc 43- 201233333 A smaller percentage means faster digestibility and increased digestion. For powder formulations, the protein digestibility or extent of the low calorie infant formula of the present invention (expressed as a percentage of total protein fresher than 5000 Da after in vitro gastrointestinal digestion as described herein) is about 13 5% or 13 5%. The following includes about below, about 11% or less, about 9 〇〇/〇 or 9.0% and about 6.0% or less 且% and especially from about 5 to about 13.5. /. . In an embodiment wherein the infant formula is autoclaved, the protein digestibility or extent (expressed as a percentage of total protein greater than 5,000 after in vitro gastrointestinal digestion as described herein) is about 8% or U%. Hereinafter, it includes about 7% or less, about 6% or less, about 5% or less, about 5.0% or less, about 4,000% or less, and about 3% or about 3%. Below %, and further including about 2.0 ° /. Up to about 0.0%. In an embodiment wherein the infant formula is aseptically sterilized, & white matter digestibility or degree (expressed as a percentage of total protein having a MW greater than 5 后 after in vitro gastrointestinal digestion as described herein) is about 9.0% or 9.0% or less, including about 7% or less, about 6.00% or less, about 5.0% or less, about 3.0% or 3.0. /. The following 'and further includes from about 2% to about 5%. The rate or extent of protein digestibility can also be expressed by the amount of insoluble protein present in the infant formula after parenteral digestion as described herein. Techniques for determining the insoluble protein content are set forth in the examples of the present invention. A small amount of insoluble protein indicates a faster digestibility and an increased degree of digestion. 0 Protein digestibility or degree of the low calorie infant formula of the present invention (indicating that 161200.doc 201233333 is present after in vitro gastrointestinal digestion as described herein) The amount of insoluble protein in the formulation) is about 15 mg/L or less than 15 mg/L, including about 110 mg/L or less, about 75 mg/L or less, about 75 mg/L or less. 50 mg/L or less, and below about 25 mg/L or 25 mg/L, and especially from about 20 mg/L to about 11 mg/L. As discussed herein, processing an infant formula and treating the dairy product, particularly at elevated temperatures, can increase the reaction of the amino acid with the sugar, known as the Mena reaction. These reactions reduce the bioavailability of the amino acid by limiting the accessibility of the proteolytic enzyme. It has now been found that the Mena reaction in the low calorie infant formula of the present invention is less advanced than the full calorie formulation. This can be illustrated by measuring the content of the intestine formula of the digested infant formula. Specifically, it has been found that the amount of the melanine reaction label of the low calorie infant formula of the present invention after the in vitro parenteral digestion as described herein is lower than the total calorie formula. Thus, in one aspect, the invention provides an infant formula comprising about 2.5 or 2.5 or less, including about 1.5 or less, about 1. 〇 or ι, after in vitro gastrointestinal digestion as described herein.梅 The following is about 〇9 or 〇_9〇 and especially about 0.7 to about 1. The amount of 〇 (mg/丨〇〇g product) of the Mena reaction label lysine. Method of Preparation The infant formula of the present invention can be prepared by any of the known or other preparative techniques effective for preparing the solid or liquid form of the selected product. A variety of such techniques are known for use in any given product form (such as a nutritional liquid or powder) and can be readily applied to the infant formula described herein by those of ordinary skill in the art. 161200.doc •45· 201233333 Thus the infant formula of the present invention can be prepared from a variety of known or otherwise effective methods of formulation or preparation. For example, in a suitable preparation method, at least two separate slurries are prepared, which are then blended together, processed, standardized, and finally sterilized to form a sterilized dad-sterilized infant formula or sterile Treated and filled to form a sterile sterile infant formula. Alternatively, the slurries can be blended together, heat treated, normalized, second heat treated, evaporated to remove water and spray dried to form a powdered infant formula. The slurry formed may include a carbohydrate-mineral (CH〇_MIN) slurry and a protein-in_oil/PIO slurry. Initially 'by dissolving selected carbohydrates (eg lactose, galactooligosaccharides, etc.) in hot water with stirring' followed by the addition of minerals (eg potassium citrate, magnesium sulphate, chlorinated sodium, chlorine) Cholesterol test, etc.) to form CHO-ΜΙΝ. The resulting CHOPIN slag is kept under continuous heating and moderate agitation until it is subsequently blended with other prepared slurries. By heating and mixing oils (such as high oleic safflower oil, soybean oil, coconut oil, monoglyceride, etc.) and emulsifiers (such as soy lecithin), and then adding oil-soluble vitamins under continuous heating and mixing , mixed carotenoids, proteins (such as milk protein concentrates, milk protein hydrolysates, etc.), horns and vegetables (if present), carbonated or acid-filled (if present), and Ar a oil and DHA oil (In some embodiments) to form a PI(R) slurry. The resulting ρι〇 slurry is maintained under continuous heating and moderate mixing until it is subsequently blended with other prepared materials. Heating the water and then with sufficient agitation with the CHO-MIN slurry, skim milk (if present) and The PIO slurry is combined. The pH of the resulting blend was adjusted to 6.6 - 161200.doc -46 - 201233333 7 · 〇 ' and the blend was maintained under moderate heating and stirring. In some embodiments 'ARA oil and DHA oil are added at this stage. The composition is then processed by high temperature short time (HTST) during which the composition is heat treated, emulsified and homogenized, and then cooled. Water-soluble vitamins and ascorbic acid are added, pH is adjusted to the desired range if necessary, perfume (if present) is added and water is added to obtain the desired total solids content. For the aseptically sterilized infant formula, the emulsion is subjected to a second heat treatment via a sterile processor, cooled and then inoculated into a suitable container. For sterilized infant formula, the emulsion is packaged in a suitable bar and finally sterilized. In some embodiments, the emulsion may be further diluted, heat treated, and packaged to form the desired ready-to-eat or concentrated liquid, or may be heat treated and then processed and packaged as a reconstitutable powder (eg, spray dried, dry mixed, gathered Knot). Spray-dried powder infant formulas or dry blended powder infant formulas can be prepared by any known or other effective technique set suitable for the preparation and formulation of nutritional powders. For example, when the powdered infant formula is a spray dried nutritional powder, the spray drying step can similarly include any spray drying technique known or in a manner suitable for the preparation of nutrients. A variety of methods are known; and spray drying methods and techniques are used in the field of nutrition, both of which are suitable for the preparation of the spray-dried powder infant formula herein. After drying, the finished powder is in a suitable container. Method of Use The low calorie infant formula of the present invention can be administered orally to infants, including term infants, premature infants, and or newborns. A low-calorie infant formula can be administered to a premature infant and/or newborn as a source of nutrients for the infant and/or can be used to address one or more of the diseases or conditions discussed herein, or can be used to provide one or A variety of benefits described in this article 1 group towel may be actually suffering from a disease or condition, or may have a risk of disease or condition (due to family history, etc.), may be disease or disease Sensitive, or may require treatment/control/mitigation of a disease or condition. Infant formulas will usually be administered daily in intakes suitable for the age of the infant. Therefore, because the methods disclosed herein are related to certain subgroups or subcategories of infants (eg, requiring treatment or control of money or condition) Infants) and usually with respect to the standard infant population 'and therefore not all infants can benefit from all of the method embodiments disclosed herein. For example, the method of the present invention can comprise administering an infant- or a plurality of low-calorie formulations of the present invention at an average intake as described herein. In some embodiments, the amount of formula in which the newborn is increasing is provided in the most life-reducing week. The equivalent is most typically on the average of up to about 1 ml/day during the first day of life, and is on average from about 200 to about ml/day during the remainder of the three-month period of the newborn's meal. , including from about fine to about cc/day and also from about 250 to about 500 ml/day. It should be understood, however, that the amount may vary significantly from a particular newborn and its unique nutritional needs during the first & weeks or months of life and the nutrient and caloric density of the infant formula. In some embodiments, the method of the present invention may be directed to the first few weeks or months of life (preferably during at least the first week of life, more preferably at least the first two weeks of life and including up to about 3 of life) Newborns of the month). Thereafter, the infant can be converted to a conventional infant formula (alone or in combination with the human milk group 161200.doc 48-201233333). The methods described herein can include administering two or more different infant formulas to an infant. For example, infants with low calorie 1-2 days of infant formula can be administered on the first two days after birth and then low calorie infant formula 3-9 can be administered on day 3-9 of birth. The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 10th day after birth. Unless otherwise stated, the infant formula used in the methods described herein is a nutritional formula and can be in any product form, including ready-to-feed liquids, concentrated liquids, reconstituted powders, and the like. In embodiments where the infant formula is in powder form, the method may further comprise reconstituting the powder with an aqueous vehicle (most typically water or human milk) to form the desired caloric density, followed by oral or enteral feeding of the infant. The powder formulation is reconstituted with sufficient water or other suitable fluid, such as human milk, to produce the desired caloric density and the amount of food required to feed a baby. The infant formula may also be sterilized by autoclaving or autoclaving prior to use. Other embodiments are described in more detail below. Nutrition In one aspect, the invention relates to a method of providing nutritional nutrition to an infant. The method comprises administering to the infant one or more of the low calorie, low micronutrient infant formulas of the invention. Such methods can include daily administration of an infant formula, including administration in a daily intake as described above. In some embodiments, the infant is a newborn. As described above, any low-calorie, low-micronutrient infant of the present invention can be used in this method with 161200.doc •49-201233333. The low micronutrient infant formula contains micronutrients and at least one macronutrient selected from the group consisting of protein f, carbohydrates, fats, and combinations thereof. In one embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to less than 6 〇〇 kcal/L, wherein at least 65% of the micronutrients are from about 30% to about 80% of the conventional micronutrient amount. The amount is included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to about 360 kcal/L, of which at least 45. /. The micronutrients are included in the infant formula (in unit volume) in amounts ranging from about 3% to about 65% of the amount of the corresponding micronutrient. In another embodiment, the low micronutrient infant formula has an energy content of from about 36 〇 kcai/L to less than 6 〇〇 kcal/L, wherein at least 3 〇〇/0 of the micronutrient is about 55 of the conventional micronutrient amount. Amounts from % to about 80% are included in the infant formula (in unit volume). The low calorie infant formula can be formulated on Day 1-2 and/or Formulated on Day 3-9. The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1_2 days formula)' and then a low-calorie infant formula (with high or low micronutrient content) with an energy content of about 360 kcal/L to less than 600 kcai/L from day 3 to day 9 after birth (eg 3-9 days formula). The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 1st day after birth. I6I200.doc 201233333 Buffering capacity The buffering capacity of infant formula has been found to correlate with the energy content of the formula. To be sure, the buffering capacity of infant formula has been found to decrease with decreasing energy content. Thus, the low calorie infant formula of the present invention advantageously has an improved (i.e., lower) cushioning capacity compared to a full calorie infant formula, and in some embodiments' has a lower buffering capacity than human breast milk. Therefore, the low-calorie infant formula of the present invention can be used to increase the gastric acidity of infants, especially newborns, and to regulate the growth of gastrointestinal flora of infants, including controlling (eg, reducing) the growth of pathogenic microorganisms in the gastrointestinal tract of infants, promoting the growth of beneficial microorganisms in the gastrointestinal tract of infants, and increasing The effectiveness of inactivating pathogens that are orally ingested. Without wishing to be bound by any particular theory, the pH value of the gastrointestinal tract of the breast-fed infant is stronger than that of the infant with the full-calorie formula, which contributes to the inactivation of the pathogens that are orally ingested and provides a more suitable natural An environment that is beneficial for the growth of gastrointestinal flora. This is due, at least in part, to the low buffering capacity of human breast milk. Since the buffering capacity of the low calorie infant formula of the present invention is comparable to or lower than that of human breast milk, the gastric acidity of the infants fed by the low calorie infant formula disclosed herein will be more closely similar to those seen in breastfed infants. Thus, in one aspect, the present invention is directed to increasing the acidity of the gastric juice of an infant (e.g., by lowering the pH of the gastric juice) to about the same extent as breastfed infants. The method comprises identifying an infant whose gastric acid is reduced in acidity and administering to the infant any of the low calorie infant formulas of the present invention. The baby is preferably a newborn. The "stomach acidity" refers to the acidity of the stomach and can be measured using a pH value of 161200.doc •51 · 201233333. For example, gastric acidity increases as the pH of the stomach contents decreases. As used herein, the term "lower gastric acidity" means that the gastric acidity of the infant is lower than the gastric acidity normally seen in breastfed infants. Infants with reduced gastric acidity can be identified as having a reduced or lower rate of pathogen community formation in the gut. After administration of the low calorie infant formula of the present invention, the gastric acidity of the infant is increased to the extent typically found in breastfed infants. As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a Day 1 or Formula 3-9 formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L to about 500 kcal/L. The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a 1-2 day formulation of an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life, and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 36 〇 kcal/L to less than 600 kcal/L. The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the second day after birth. Formulations for infants will usually be administered daily as ingested above. In another aspect, the present invention relates to a method for increasing the acidity of the gastric juice of an infant comprising administering to the infant any of the low micronutrient infant formulas of the present invention. The low micronutrient infant formula comprises micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof. In one embodiment, the low micro-capacity 161200.doc •52·201233333 nutrient infant formula has an energy content of from about 200 kcal/L to less than 6〇〇kcal/L, wherein at least 65% of the micronutrients are known as corresponding micronutrients. Amounts from about 30% to about 80°/〇 are included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to about 360 kcal/L, wherein at least 45% of the micronutrient is from about 30% to about 65% of the amount of the corresponding micronutrient. The amount is included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 36 〇 kcal/L to less than 600 kcal/L, wherein at least 30% of the micronutrient is from about 55% to about 80% of the corresponding micronutrient amount. The amount of % is included in the infant formula (in unit volume). The low calorie infant formula can be formulated on Day 1_2 and/or Formulated on Day 3-9. The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1-2 days formula). A low calorie infant formula (with high or low micronutrient content) (e.g., day 3-9 formulation) with an infant energy content of from about 360 kcal/L to less than 600 kcal/L can then be administered on days 3-9 after birth. The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the first day after birth. In embodiments in which the low calorie infant formula has a low micronutrient content, the micro s nutrient included in the formula may be any of the above contents. Formulations for administration to infants will usually be administered daily as ingested above. 161200.doc • 53- 201233333 In another embodiment, the invention relates to a method of modulating the growth of a beneficial gastrointestinal flora in an infant. The method comprises identifying an infant with an imbalance in gastrointestinal flora growth and administering to the infant any of the low calorie infant formulas of the invention. Babies are better for newborns. For the purposes of the present invention, gastrointestinal flora growth can be modulated by promoting the growth of microorganisms that are beneficial to GI health and/or controlling the growth of pathogenic microorganisms. The growth of pathogenic microorganisms can be controlled by inhibiting, inhibiting, killing, inactivating, destroying or otherwise impeding the growth of pathogenic microorganisms such that the growth rate of such microorganisms is slowed or stopped. Infants with unbalanced growth of GI flora include one or more pathogenic microorganisms in the gastrointestinal tract of infants than those normally found in breastfeeding 4c and/or one or more beneficial microbial contents in the gastrointestinal tract of infants are lower than those normally found in breastfed infants Infant content. These infants can be identified by a lower rate of formation of pathogenic bacteria in the gut. After administration of the low calorie infant formula of the present invention, the gastric acidity of the infant is increased to a similar extent as is generally seen in breastfed infants, resulting in a GI environment that promotes the growth of beneficial microbes and controls the growth of pathogenic microorganisms. As described above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content, or in some embodiments ' may have a high micronutrient content and may be a 1st - 2 day formulation or a 3-9 day formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L formulation to about 500 kcal/L formulation. The sin method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a 1_2 161200.doc •54·201233333 day formula having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life, and is then born. The 3rd-9th day formulation with an energy content of about 36〇kcal/L to less than 600 kcal/L was administered on days 3-9. The 3rd-9th day infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 1st day after birth. Formulations for infants will usually be administered daily as ingested above. In another aspect, the invention relates to a method of modulating the growth of a gastrointestinal flora of an infant comprising administering to the infant any of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. The low micronutrient infant formula can be any of the above formulas. The methods can further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low-heat S infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg,丨_2 days formula). A low-calorie infant formula (with high or low trace s nutrient 3) with an infant energy content of about 360 kcal/L to less than 600 kcai/L can then be administered on days 3 to 9 after birth (eg, 3-9) Day formula). The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 1st day after birth. In embodiments where the low calorie infant formula has a low micronutrient content, the amount of micronutrient included in the formulation can be any of the above levels. Formulations for administration to infants will usually be administered daily as ingested above. Beneficial microorganisms are microorganisms that maintain gastrointestinal tract and exhibit physiological, immunomodulatory and/or antimicrobial effects such that they are found to be capable of preventing and treating GI diseases and/or conditions. Non-limiting microorganisms 161200.doc -55- 201233333 Qualitative examples include any one or more of the following microorganisms: Genus, including Lactobacillus acidophilus (I. aczWop/n'/w·?), Lactobacillus brevis (Ζ· amy/ovorw·?), Lactobacillus brevis (Z. AreW·?), Lactobacillus bulgaricus (Z. h/garicw·?), Lactobacillus dry bacterium, subspecies (Z. Casez· 5/?/7. Caiez·), Lactobacillus ssp. rhamnoides (L. ciiiez· ίρρ. and /zawwoswi), Lactobacillus crispus (Ζ«· crh/yaiwi), Lactobacillus delbrueckii Subspecies (L. i/e/ftrwecA: iz·w/?. Lac"··?), Lactobacillus aceti (L. /erme«iM/n), Lactobacillus helveticus (! Zie/vaiicws), Lactobacillus johnsonii <· yo/mscm/i·), co-dry, Lactobacillus ([· pwacase O, L. pewiosws, Lactobacillus plantarum (Z. /?/) <2«iarwm), L. lactis (Z. rei/ierz·) and Lactobacillus sake (Z·sak); genus 5 (/ii/o6 atcieriwm), including animal bifidobacteria ( 5. Bifidobacterium bifidum (5., Bifidobacterium shortum (Β·fcreve), Bifidobacterium infantis (5. /«/ <3« along) and B. rhizogenes (when longum) \ genus genus (genus Pe mountain · ococew·?) 'including lactic acid bacteria (P. aeii / z7acnW); Propionibacterium (genus. Propionibacterium) ), including R acidipropionici, Propionibacterium faecalis (household./reMi^"rez'c/n7), Propionibacterium japonicum (·Ρ. and Propionibacterium faecalis (P. ; and genus genus (genus • Sirepiococcws), including Streptococcus lactis (51· crewor/i), lactococcus ( <S. / acn'i) and Streptococcus thermophilus (S.; and combinations thereof. Non-limiting examples of pathogenic microorganisms that can be grown by methods disclosed herein include any one or more of the following pathogenic microorganisms: Bacteria, such as Clostridium (genus C/oWrWww) 'including C. difficile ·, Dayang De Wi [Escherichia coli/E. colV) ', Lonely Phoenix 161200.doc -56- 201233333 π.); Salmonella (/w〇 plus α/α w ); Shigella (*S/ny//a W.); Aspergillus (Cimp/〇^hcier); gas-producing unit Bacterium M (Aer〇m〇nas sp.)., Staphyl〇c〇ccus sp • Pseudomonas (PseMc/owonw); and parasites such as P. cerevisiae (Gkdk) Sigh.); and cryptosporium (Crw? i〇w (8) · India); and combinations thereof. Protein Digestion and Hydrolysis It has been found that the digestibility and extent of protein in infant formula are related to the energy content of the formula. Specifically, it has been found that the digestibility of the protein in the infant formula increases as the energy content of the formula decreases. Thus, the low calorie infant formula of the present invention advantageously has improved (e.g., faster) digestibility as compared to a full calorie infant formula. Thus, the low calorie infant formula of the present invention can be used to improve formulation tolerance, protein digestion, and nutrient (and especially protein) absorption in infants and especially newborns. Thus, in one aspect, the present invention relates to a method of improving protein digestion in infants. The method comprises inflicting a baby who has experienced protein insufficiency and administering to the infant any low-calorie infant of the invention. The baby is preferably a newborn. As used herein, the term "modified protein digestion" includes increasing the rate of protein t digestion (or hydrolysis) in an infant formula and/or increasing the degree of digestion of the protein in the infant formula upon contact with the digestive enzyme. This protein digestion modification can use any of the measures described herein, including, for example, the median weight of the protein after digestion, the molecular weight of the protein after digestion is greater than 5 Da Daltons, and/or the amount of protein present after digestion. The amount of insoluble protein is 161200.doc •57· 201233333. As used herein, the term "protein insufficiency" means that the amount of protein actually present in the nutritional product consumed by the infant is less than the amount of protein normally digested by the breastfed infant. Infants experiencing protein insufficiency may display signs of formulation intolerance and may therefore be identified using any of the formula intolerance symptoms described herein. It may also be identified by diarrhea, soft stools, fart and/or bloating. baby. The protein digestibility and extent were improved after administration of the low calorie infant formula of the present invention. As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a 1st - 2 day formulation and/or a 3rd - 9th day formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L formulation to less than 600 kcal/L formulation. The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a 1-2 day formulation of an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life, and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 360 kcal/L to less than 600 kcal/L. Formulas 3-9 can be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) can be administered on the 10th day after birth. Formulations for administration to infants will usually be administered daily as ingested above. In another aspect, the present invention relates to a method for improving protein digestion in infants, which comprises administering to a baby any of the low micronutrient infant formulas of the present invention. The infant is preferably a neonate. The low micronutrient infant formula contains a trace amount of 16120 〇. <ΐ()ς -58- 201233333 S nutrient and sputum are selected from the group consisting of macronutrients consisting of proteins, carbohydrates, fats and combinations thereof. In one embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to less than 600 kcal/L, wherein at least 65% of the micronutrient is included in an amount of from about 3 G% to about the amount of the corresponding micronutrient. In infant formula (in unit volume). In another embodiment, the energy content of the low micronutrient infant formula is ''spice 200 kcal/L to about 360 kcal/L, wherein at least 45% of the micronutrient is about 3% of the amount of the corresponding micronutrient to Approximately 65% of the amount is included in the infant formula (in unit volume). In another embodiment, the low micronutrient infant formula has an energy content of from about 36 〇 kcal/L to less than 600 kcal/L, wherein at least 30 〇/〇 of the micronutrient is from about 55% to about 55% of the corresponding micronutrient amount. 80% of the amount is included in the infant formula (in unit volume). The low calorie infant formula can be formulated on Day 1-2 and/or Formulated on Day 3-9. The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having a high or low micronutrient content) having an infant energy content of from about 2 〇〇 kcal/L to about 360 kcal/L is administered during the first two days of life ( For example, the 1st day formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 360 kcal/L to less than 600 kcal/L can be administered on days 3 to 9 after birth (eg, Days 3-9) . Formulas 3-9 can be administered after the 9th day after birth, or higher calorie formulas (including full calorie formula) can be administered on the 1st day after birth. In embodiments where the low calorie infant formula has a low micronutrient content, the amount of nutrient included in the formula may be any of the above. Formulations for infants will usually be administered daily as described above. In another embodiment, the invention relates to a method of improving protein absorption in an infant. The method comprises identifying an infant experiencing protein insufficiency; and administering to the infant any of the low calorie infant formulas of the invention. An infant undergoing protein insufficiency can be identified using any of the criteria described herein for identifying infants undergoing protein insufficiency. As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a 1st or 2nd day formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L formulation to less than 600 kcal/L formulation. The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a 1-2 day formulation of an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life, and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 360 kcal/L to less than 600 kcal/L. Formulations 3-9 can be administered after the 9th day after birth, or higher calorie formulas (including full calorie formula) can be administered on the 1st day after birth. Formulations for administration to infants will usually be administered daily as ingested above. In another aspect, the invention relates to a method of improving protein absorption in an infant comprising administering to the infant any of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. The low micronutrient infant formula can be any of the above formulations. 161200.doc -60- 201233333 These methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low-calorie infant formula (having a low or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, I·〗 Day recipe). A low-calorie infant formula (having a high or low micronutrient content) with an infant energy content of about 3 60 kcal/L to less than 600 kcal/L can then be administered on days 3 to 9 after birth (eg, Day 3-9 formulation). The 3rd-9th infant formula may be administered after the 9th day after birth, or a higher calorie formula (including a full calorie formula) may be administered on the 1st day after birth. In embodiments where the low calorie infant formula has a low micronutrient content, the amount of micronutrient included in the formulation can be any of the above levels. Formulations for administration to infants will usually be administered daily as ingested above. Tolerance The present invention is also directed to methods for improving the tolerance of infant formulas in infants. Infant formulation intolerance is a non-immune system-related response that can be confirmed by behavioral or fecal or eating patterns, such as increased cough or vomiting, increased frequency of bowel movements, more watery stools, increased black stools and crying . Infant Formulas Imperfections are most often associated with gastrointestinal symptoms (eg, fecal morphology, fart, cough) and behavioral characteristics (eg, formula acceptance, crying, and shouting). Infants with formulation intolerance may also experience gastroesophageal reflux. It has been unexpectedly found that infants are more tolerant of infant formulas with lower energy content than full calorie formulas. Specifically, it has been found that low-calorie infant formulas exhibit faster protein hydrolysis and digestibility, produce less Mena reaction products (which cannot be broken down and absorbed) and have a faster stomach I61200 compared to the full-calorie formula. Doc -61 - 201233333 Emptying rate. When the gastric emptying is faster, the gastroesophageal reflux can be reduced and the formulation can be improved. Thus, the low calorie infant formula of the present invention can be used to reduce the frequency of infant fart and/or cough. The low calorie infant formula of the present invention can also be used to increase the gastric emptying rate of an infant and to reduce the amount of the Mena reaction product produced by the food formulation as compared to the whole calorie infant formula. A low-calorie infant formula can be administered to any infant (preterm or term) and in particular any infant who can benefit from an infant formula that has low energy content and is highly tolerant. In some embodiments, the neonate is administered a low calorie infant formula of the invention. Thus, in one aspect, the invention is also directed to a method of improving infant formula tolerance in infants. The method comprises identifying an infant suffering from infant formula intolerance and administering to the infant any one or more of the low calorie infant formulas of the invention. Infants with infant formula intolerance may include infants with one or more of the symptoms of formulation intolerance. These symptoms include (but are not limited to) fecal or eating patterns, such as increased cough or beta vomiting; increased frequency of bowel movements; more watery stools; black stools; crying, shouting, fart increase; formula. Some or all of the formulation intolerance symptoms may be reduced or eliminated upon administration of the low calorie infant formula of the present invention. As noted above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula may have a low micronutrient content or, in some embodiments, may have a high micronutrient content and may be a 12th day formulation or a 3rd-9 day formulation. In one embodiment, the low calorie infant formula has an energy content of from about 200 to about 6 kilocalories per liter of formula. 161200.doc •62· 201233333 The method may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a 1-2 day formulation of an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life, and then 3 to 9 after birth. A 3-9 day formulation with an energy content of from about 36 〇 kcal/L to less than 600 kcal/L. The formulation may be administered on Days 3-9 after the ninth day after birth, or may be administered to a more caloric formula (including a full calorie formula) on the first day after birth. Formulations for administration to infants will usually be administered daily as ingested above. In another aspect, the invention relates to a method of improving infant formula tolerance in an infant comprising administering to the infant any of the low micronutrient infant formulas of the invention. The baby is preferably a newborn. The low micronutrient infant formula comprises micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof. In one embodiment, the low micronutrient infant formula has an energy content of from about 2 〇〇 kcal/L to less than 6 〇〇 kcal/L, wherein at least 65% of the micronutrient is from about 30% to about 10% of the corresponding micronutrient amount. 80. /. The amount is included in the infant formula (in units of juice). In another embodiment, the low micronutrient infant formula has an energy content of from about 200 kcal/L to about 360 kcal/L, wherein at least 45% of the micronutrient is from about 3% to about 65% of the conventional micronutrient amount. The amount is included in the infant formula (in terms of unit volume). In the embodiment, the low micronutrient infant formula has an energy content of about 36〇kcal/L to less than 6〇〇^, wherein at least Μ% of the micronutrients are conventionally corresponding. Micronutrients

量之約55%至約80%之晉白μ M &lt;置包括於嬰兒配方中（以單位體積 計）。减量嬰兒配方可為第1-2天配方及/或第3_9天配 161200.doc •63- 201233333 方。 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而言，在一個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之低 熱量嬰兒配方（具有高或低微量營養素含量）（例如第1_2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 3 60 kcal/L至小於600 kcal/L之低熱量嬰兒配方（具有高或低 微量營養素含量）（例如第3-9天配方）。可視情況在出生後 第9天過後投與第3-9天配方，或可在出生後第10天開始投 與較尚熱量配方（包括全熱量配方在低熱量嬰兒配方具 有低微量營養素含量之實施例中，配方中所包括之微量營 養素量可為任一上述含量。投與嬰兒之配方將通常以如上 述攝取量每日投與。 在另一實施例中，本發明係關於抑制嬰兒胃食道逆流之 方法該方法包含鑑別罹患胃食道逆流之嬰兒及對該嬰兒 投與任一或多種本發明之低熱量嬰兒配方。嬰兒較佳為新 生兒。 畠發生月食道逆流（GER)時’胃含物逆流入食道中且自 口中流出，引起反胃、咳吐及/或嘔吐。GER症狀包括咳 吐、嘔吐、咳嗷、煩躁、進食不良、血便及其組合。當發 生GER時，嬰兒亦可能咳嗽、喊叫或緊張。為達成本發明 之目的，術語「抑制胃食道逆流」意欲包括治療、預防 GER及/或其至少一種症狀及/或降低其發生率。不希望受 任何特定理論約束，咸信本發明之低熱量嬰兒配方與全熱 161200.doc -64- 201233333 量配方相比具有較快胃排空速率（亦即内含物穿過胃之速 率）’其引起胃食道逆流減少* 如上所述，任何本發明之低熱量嬰兒配方均可用於此方 法。低熱量嬰兒配方可具有低微量營養素含量，或在一些 實施例中，可具有高微量營養素含量，且可為第1 _2天配 方或第3-9天配方。在一個實施例中，嬰兒配方之能量含 量為約200 kcal/L配方至小於600 kcal/L配方。 該方法亦可進一步包含投與嬰兒兩種或兩種以上不同嬰 兒配方。舉例而言，在一個實施例中，在出生後頭兩天期 間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之第1-2 天配方’且接著在出生後第3至9天投與能量含量為約36〇 kcal/L至小於600 kcal/L之第3-9天配方。可視情況在出生 後第9天過後投與第3-9天配方’或可在出生後第天開始 投與較高熱量配方（包括全熱量配方投與嬰兒之配方將 通常以如上述攝取量每日投與。 在另一態樣中，本發明係關於抑制嬰兒胃食道逆流之方 法，其包含投與嬰兒任一或多種本發明之低微量營養素嬰 兒配方。嬰兒較佳為新生兒。低微量營養素嬰兒配方可為 任一上述配方。 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方。舉例而言，在一個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約2〇〇 kcal/L至約360 kcal/L之低 熱量嬰兒配方（具有高或低微量營養素含量）（例如第卜2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 161200.doc •65- 201233333 360 kcal/L至小於600 kcal/L之低熱量嬰兒配方（具有高或低 微量營養素含量）（例如第3_9天配方）。可視情況在出生後 第9天過後投與第3_9天配方，或可在出生後第1〇天開始投 與較局熱量配方（包括全熱量配方）。在低熱量嬰兒配方具 有低微量營養素含量之實施例中，配方中所包括之微量營 養素量可為任一上述含量。投與嬰兒之配方將通常以如上 述攝取量每日投與。 在另一態樣中’本發明係關於提高嬰兒之胃排空速率之 方法，其包含投與嬰兒任一或多種本發明之低微量營養素 兒配方备兒較佳為新生兒。低微量營養素嬰兒配方可 為任一上述配方。 該等方法亦可進一步包含投與嬰兒兩種或兩種以上不同 嬰兒配方》舉例而言，在一個實施例中，在出生後頭兩天 期間投與嬰兒能量含量為約200 kcal/L至約360 kcal/L之低 熱量嬰兒配方（具有高或低微量營養素含量）(例如第丨_2天 配方）。接著可在出生後第3至9天投與嬰兒能量含量為約 360 kcal/L至小於600 kcal/L之低熱量嬰兒配方（具有高或低 微量營養素含量）（例如第3_9天配方）。可視情況在出生後 第9天過後投與第3-9天配方，或可在出生後第1〇天開始投 與較问熱量配方（包括全熱量配方）。配方中所包括之微量 營養素量可為任一上述含量。投與嬰兒之配方將通常以如 上述攝取量每日投與。 套組 此外，本發明提供包含兩種或兩種以上本發明之低熱量 161200.doc -66 - 201233333 嬰兒配方之套組。 舉例而言，在一些實施例中，套組可包含至少一種第i 2天配方及至少一種第3-9天配方。套組較佳將包含足量的 第1-2天配方以在出生後頭兩天期間提供嬰兒充分營養， 及足量的第3-9天配方以在出生後至少第3·9天提供嬰兒充 分營養。套組中包括之嬰兒配方可呈任何合適形式，包括 (例如）即食型液體、濃縮液體、粉末或其組合。套組可包 括低熱量、低微量營養素配方及/或低熱量、高微量營養 素配方。 套組可視情況進一步包含套組使用說明書。舉例而言， 說明書可描述如何使用配方，例如可指示應在出生後頭兩 天投與第1-2天配方且應在出生後第3_9天投與第3_9天配 方，可描述配方之每日投藥時程；及/或可描述如何實踐 任何本揭示案中描述之方法。說明書可進一步視情況描述 如何復原套組中所包括之任何粉末嬰兒配方。 除嬰兒配方及視情況選用之說明書外，套組亦可包括其 ^ 諸如或多個各種大小之奶瓶（baby bottle)、一 或夕個各種大小之奶瓶襯塾、奶瓶奶嘴及其類似物。 實例 1下實例說明本發明之嬰兒配方及方法之特定實施例 或特徵。實例係僅出於說明目的提供且不應視為限制 日月 &gt; y- 不偏離本發明之精神及範疇的情況下對其做 出多種變化。除非 '、另有說明，否則所有例示量均為以組合 物之總重量計之重量百分比。 161200.doc -67- 201233333 除非另有說明，否則根據本文中所描述之製備方法製備 之殺菌釜滅菌及無菌滅菌配方為即食型液體配方。 實例1-8 在該等實例中，製備2盘司具有高或低微量營養素含量 之第1-2天嬰兒配方及第3-9天嬰兒配方。用於製備配方之 成分闡述於以下表1及2中。 表1 :第1-2天配方 單位 配方1 (第1-2天） 配方2 (第1-2天） 配方3 (第1-2天） 配方4 (第1-2天） 能量 Kcal/L 270 270 250 250 微量營養素含量 低 低 高 而 成分(每1000 Kg批次含 量） 水 kg 適量 適量 適量 適量 乳糖 kg 23.2 23.1 15.5 15.2 脫脂乳粉 kg 11.0 11.0 11.0 11.3 半乳寡醣 kg 4.40 4.40 4.40 4.40 高油酸紅花子油 kg 5.34 5.35 5.33 5.37 大豆油 kg 4.00 4.00 3.99 4.00 椰子油 kg 3.82 3.82 3.81 3.84 乳清蛋白濃縮物 kg 2.70 2.70 2.70 2.86 1 NKOH g 1340 1.40 1340 1340 氩氧化鉀 g 67.0 70.0 67.0 67.0 磷酸氫鈣 g 327.1 249.8 1090 770.2 檸檬酸鉀 g 3.10 1.24 1370 1240 檸檬酸鈣 g 351.0 578.8 752.6 768.9 抗壞血酸 g 727.5 727.5 727.5 727.5 ARA油 g 367.9 367.9 367.9 367.9 核苷酸-膽鹼預混物 g 328.5 328.5 328.5 328.5 磷酸二鈣 g ___ ... •講 ___ 氯化鎂 g 16.8 102.6 460.9 450.7 161200.doc -68- 201233333 單位 配方1 (第1-2天） 配方2 (第1-2天） 配方3 (第1-2天） 配方4 (第1-2天） 氯化納 g 45.7 28.5 325.8 186.7 大豆卵磷脂 g 143.0 143.0 143.0 143.0 蒸顧後的單酸甘油醋 g 143.0 143.0 143.0 143.0 維生素/礦物質/牛磺酸 預混物 g 31.4 57.1 157.0 157.0 牛磺酸 g 9.60 17.5 48.0 48.0 m-肌醇 g 6.97 12.7 34.85 34.85 硫酸鋅 g 3.21 5.85 16.07 16.07 菸鹼醯胺 s 2.05 3.73 10.24 10.24 泛酸鈣 g 1.23 2.23 6.14 6.14 硫酸亞鐵 g 1.07 1.95 5.37 5.37 硫酸銅 mg 377 686 1890 1890 鹽酸維生素B1 mg 318 578 1590 1590 維生素B2 mg 140 255 701 701 鹽酸維生素B6 mg 128 234 642 642 葉酸 mg 43.2 78.5 216 216 硫酸錳 mg 36.6 66.5 183 183 生物素 mg 12.4 22.6 62.0 62.0 碰酸鈉 mg 7.44 13.5 37 37 氰鈷胺素 mg 0.990 1.8 4.95 4.95 DHA油 s 137.9 137.9 137.9 137.9 氯化鉀 g 46.3 52.4 視需要 60.7 氣化膽驗 g 58.9 21.5 88.9 54.0 硫酸亞鐵 g 5.80 23.20 60.9 60.9 角叉菜膠 g 175.0 175.0 175.0 175.0 維生素A、D3、E、K1 g 22.8 19.0 47.5 47.5 RRR乙酸α-生育酚 g 4.61 3.84 9.6 9.6 棕搁酸維生素A mg 867 721.5 1800 1800 維生素K1 mg 50.2 41.8 104.5 104.5 維生素D3 mg 6.08 5.06 12.65 12.65 檸檬酸 g 29.8 29.8 29.8 29.8 混合類胡蘿勤素預混物 g 23.8 23.8 23.8 23.8 番茄紅素 mg 119 119 119 119 161200.doc •69- 201233333 單位 配方1 (第1-2天） 配方2 (第1-2天） 配方3 (第1-2天） 配方4 (第1-2天） 葉黃素 mg 50 50 50 50 β-胡蘿蔔素 mg 26.2 26.2 26.2 26.2 肌醇 g 33.1 6.6 12.9 12.9 L-肉驗 g 6.38 1.31 6.38 3.28 維生素Β2 mg — 466.0 882 882 表2 :第3-9天配方 單位 配方5 (第3-9天） 配方6 (第3-9天） 配方7 (第3-9天） 配方8 (第3-9天） 能量 Kcal/L 406 406 406 410 微量營養素含量 低 低 低 尚 成分(每1000 Kg批次含 量） 水 kg 適量 適量 適量 適量 乳糖 kg 37.0 37.2 37.5 35.50 脫脂乳粉 kg 16.3 16.2 16.2 16.30 半乳募醣 kg 8.63 8.63 8.63 8.63 高油酸紅花子油 kg 7.72 7.72 7.72 7.72 大豆油 kg 5.78 5.78 5.78 5.78 揶子油 kg 5.52 5.52 5.52 5.51 乳清蛋白濃縮物 kg 4.00 4.00 4.00 4.00 1NKOH kg 1.34 1.34 0.8035 1.34 氫氧化鉀 g 67.0 67.0 40.2 67.0 磷酸氩鈣 kg 0.309 ___ ___ — 檸檬酸鉀 kg 0.00186 0.00186 0.00186 1.06 檸檬酸鈣 g 687.6 583.5 583.5 261.1 抗壞血酸 g 727.5 727.5 436.5 727.5 ARA油 g 378.2 378.2 378.2 378.2 核苷酸-膽鹼預混物 g 319.7 319.7 319.7 319.7 超微細磷酸三鈣 8 ___ 226.8 226.8 1470 氣化鎂 g 122.5 147.7 147.7 288.1 氣化納 g —— 235.8 161200.doc -70· 201233333 單位 配方5 (第3-9天） 配方6 (第3-9天） 配方7 (第3-9天） 配方8 (第3-9天） 大豆卵鱗脂 g 206.0 206.0 206.0 206.0 蒸傑後的單酸甘油醋 g 206.0 206.0 206.0 206.0 維生素/礦物質/牛磺酸預 混物 g 85.6 115.7 115.7 142.7 牛續酸 g 26.2 35.4 35.4 43.6 m_肌醇 g 19.0 25.7 25.7 31.7 硫酸鋅 8 8.76 11.8 11.8 14.61 菸鹼醯胺 g 5.59 7.55 7.55 9.31 泛酸鈣 8 3.35 4.53 4.53 5.58 硫酸亞鐵 g 2.93 3.96 3.96 4.88 硫酸銅 g 1.03 1.39 1.39 1.71 鹽酸維生素B1 g 0.8667 1.17 1.17 1.44 維生素B2 mg 382.2 516.6 516.6 637 鹽酸維生素B6 mg 350.1 473.2 473.2 584 葉酸 mg 117.7 159.1 159.1 196 硫酸錳 mg 99.7 134.7 134.7 166 生物素 mg 33.8 45.7 45.7 56.0 涵酸納 mg 20.3 27.4 27.4 34 氰链胺素 mg 2.7 3.64 3.64 4.5 DHA油 g 137.9 137.9 137.9 137.9 氣化鉀 s 108.7 111.3 111.3 129.5 氣化膽驗 g 32.4 32.4 32.4 88.9 硫酸亞鐵 g 34.8 37.5 37.5 60.9 角叉菜膠 g 175.0 175.0 175.0 175.0 維生素A、D3、E、K1 g 28.5 30.2 30.2 44.8 RRR乙酸α-生育酚 g 5.8 6.11 6.11 9.1 棕櫊酸維生素A R 1.08 1.15 1.15 1.7 維生素K1 mg 62.7 66.4 66.4 98.5 維生素D3 mg 7.6 8.04 8.04 11.9 檸檬酸 g 29.8 29.8 29.8 29.8 混合類胡蘿g素預混物 g 23.8 23.8 23.8 23.8 番茄紅素 mg 119 119 119 119 葉黃素 mg 50 50 50 50 161200.doc -71 - 201233333 單位 配方5 (第3-9天） 配方6 (第3-9天） 配方7 (第3-9天） 配方8 (第3-9天） β-胡蘿蔔素 mg 26.2 26.2 26.2 26.2 肌醇 g ... 一- ... 12.9 L-肉鹼 R 1.97 2.31 2.31 5.51 維生素Β2 g 0.70 0.699 0.699 1.50 維生素A mg ... 770 770 780 棕櫊酸維生素A mg 420 420 425 硫酸鋼 mg --- — … 391 藉由製備至少兩種獨立漿料，接著使其掺合在一起，熱 處理’標準化且最終滅菌來製備配方。最初，藉由使所選 碳水化合物（例如乳糖、半乳寡醣）在74°C -79°C下溶解於水 中’接著添加棒檬酸、氣化鎂、氣化鉀、檸檬酸鉀、氣化 膽驗及氣化鈉來製備碳水化合物-礦物質漿料。所得漿料 在49°C -60°C下保持在適度攪拌下直至其隨後與其他製備之 榮料換合在一起。 藉由在授拌下合併高油酸紅花子油、椰子油、單甘油酸 酯及大豆卵磷脂且加熱至66°C -79。(：來製備油包蛋白質激 料。靜置10-15分鐘時間後’接著向漿料中添加大豆油、 油溶性維生素預混物、混合類胡蘿萄素預混物、角叉菜 膠、維生素A、棒檬酸飼、峨酸二妈、ARA油、DHA油及 乳清蛋白濃縮物。所得油漿料在49°C -60。(：下保持在適度攪 拌下直至其隨後與其他製備之漿料摻合在一起。 水加熱至49°C -60°C且接著在充分攪拌下與碳水化合物_ 礦物質漿料、脫脂乳及油包蛋白質漿料合併。用氫氧化鉀 調節所得摻合物之pH值。該摻合物在49t：_6(rc下保持在 適度攪拌下。 161200.doc •72· 201233333 加熱所得摻合物至74°C -79°C，經單階段均質器乳化至 900-1100 psig且接著加熱至144。〇_147。〇保持約$秒。加熱 之捧合物通過快速冷卻器以使溫度降至88〇c_93&lt;5c，且接著 通過板式冷卻器以使溫度進一步降至74。〇85。(：。接著冷卻 之摻合物在2900·3100/400-600 psig下均質化，保持在 74 C-85 C下16秒且接著冷卻至2〇C-7t：。獲取用於分析測 試之樣品。混合物在2。(：-7。(：下保持在攪拌下。 獨立製備水溶性維生素（WSV)溶液及抗壞血酸溶液且添 加至經處理之摻合漿料中。藉由在攪拌下向水中添加以下 成分來製備維生素溶液：檸檬酸鉀、硫酸亞鐵、wsv預混 物、L-肉鹼、硫酸銅、維生素^、肌醇及核苷酸-膽驗預 /1物藉由將氫氧化卸及抗壞血酸添加至足以溶解該等成 分之量的水中來製備抗壞錢溶液。接著用氫氧化卸調節 抗壞血酸溶液pH值至5-9。 用氫氧化鉀調節摻合物pH值至指spH值範圍71_7 6(視 產物而不同）以獲得最佳產品敎性。接著將成品填充入 合適容器中且最終滅菌。 實例9-11 在該等實例中，製備32盘司具有高或低微量營養素含量 之無菌滅菌第3-9天嬰兒配方。用於製備配方之成分閣述 於以下表3中。 J61200.doc -73- 201233333 表3 單位 配方9(第3-9天） 配方10 (第3-9天） 配方11 (第3-9天） 能量 Kcal/L 406 410 410 微量營養素含量 低 1¾ 高 成分 每1000 kg批次含3 水 kg 適量 適量 適量 乳糖 kg 37.0 33.7 34.03 脫脂乳粉 kg 16.3 17.0 16.47 半乳寡醣 kg 8.63 8.63 8.63 高油酸紅花子油 kg 7.72 7.83 7.72 大豆油 kg 5.78 5.87 5.78 椰子油 kg 5.52 5.60 5.51 乳清蛋白濃縮物 kg 4.00 4.19 4.05 1ΝΚΟΗ kg 1.85 1.85 1.85 氫氧化鉀 8 92.5 92.5 92.5 檸檬酸鈣 g 675.0 716.8 993.9 磷酸氫鈣 g 577.4 1170 1390 抗壞血酸 g 431.7 431.7 431.7 ARA油 g 378.2 378.2 378.2 核苷酸-膽鹼預混物 g 319.7 319.7 319.7 大豆卵磷脂 g 206.0 206.0 206.0 蒸餾後的單酸甘油酯 8 206.0 206.0 206.0 角叉菜膠 g 200.0 240.0 200.0 DHA油 R 137.9 137.9 137.9 氣化鎂 g 128.9 279.3 285.9 氣化鉀 g 118.5 213.9 122.4 氣化膽驗 g 88.9 54.0 88.9 維生素/礦物質/牛磺酸 預混物 g 41.4 142.7 142.7 牛續酸 g 12.7 43.6 43.6 m-肌醇 g 9.19 31.7 31.7 硫酸鋅 g 4.24 14.61 14.61 161200.doc ·74· 201233333 單位 配方9(第3-9天） 配方10 (第3-9天） 配方11 (第3-9天） 終驗酿胺 g 2.70 9.31 9.31 泛酸鈣 g 1.62 5.58 5.58 硫酸亞鐵 g 1.42 4.88 4.88 硫酸銅 mg 497 1710 1710 鹽酸維生素B1 mg 419 1440 1440 維生素B2 mg 185 637 637 鹽酸維生素B6 mg 169 584 584 葉酸 mg 56.9 196 196 硫酸錳 mg 48.2 166 166 生物素 mg 16.4 56.0 56.0 砸酸鈉 mg 9.81 34 34 氰鈷胺素 mg 1.3 4.5 4.5 氯化納 g 32.1 65.4 231.9 維生素A、D3、E、K1 g 30.9 44.8 44.8 RRR乙酸α-生育酚 g 6.24 9.1 9.1 棕櫚酸維生素A S 1.17 1.7 1.7 維生素K1 mg 67.9 98.5 98.5 維生素D3 mg 8.22 11.9 11.9 檸檬酸 g 29.8 29.8 29.8 肌醇 8 25.8 12.9 12.9 混合類胡蘿g素預混物 g 23.8 23.8 23.8 番茄紅素 mg 119 119 119 葉黃素 mg 50 50 50 β-胡蘿蔔素 mg 26.2 26.2 26.2 硫酸亞鐵 g 16.2 60.9 60.9 L-肉驗 g 5.51 3.28 5.51 檸檬酸鉀 g 3.10 895.0 1060 維生素Β2 mg 599 1500 1500 維生素A mg ___ 780 780 棕櫚酸維生素A mg ___ 425 425 硫酸銅 mg — —— 391 藉由製備至少兩種獨立漿料，接著使其摻合在一起，熱 161200.doc •75- 201233333 處理藉t準化且接著進行無菌處理及填充來製備配方。最 :C下：斤選碳水化合物(例如乳糖、半乳寡醣)在1 ^讀於水中，接著添㈣檬酸、氯減、氣化卸、 ^料鉀、氣化膽驗及氣化納（礦物質視調配物而不同）來 1 H礦物f漿料^所得漿料在机 -6〇t：5下保 持在適度攪拌下直至其隨後與其他製備之漿料摻合在」 起〇 t藉由在授拌下合併高油酸紅花子油、椰子油、單甘油酸 s曰及大丑卵磷脂且加熱至66。。_79。匸來製備油包蛋白質漿 料靜置10 1 5分鐘時間後，接著向聚料中添加大豆油、 油浴性維生素預混物、混合類胡蘿蔔素預混物、角又菜 膠彳宁檬馱鈣、磷酸氫鈣、ARA油、dha油及乳清蛋白濃 縮物。所得油漿料在机-机下保持在適度授拌下直至其 隨後與其他製備之漿料摻合在一起。 水加熱至491-6〇t且接著在充分攪拌下與碳水化合物_ 礦物質漿料、脫脂乳及油包蛋白質毁料合併。用氫氧化卸 調節所得摻合物之{^值。該摻合物在49t： 6〇t：下保持在 適度攪拌下。 加熱所得摻合物至74t -79°C，經單階段均質器乳化至 900-1100 psig且接著加熱至144tM4rc保持約$秒。加熱 之摻合物通過快速冷卻器以使溫度降至88t&gt;c_93〇c，且接著 通過板式冷卻器以使溫度進一步降至74。〇85。(：。接著冷卻 之摻合物在2900-3100/400-600 psig下均質化，保持在 74°C-85°C下16秒且接著冷卻至2°C-7t。獲取用於分析測 161200.doc -76- 201233333 試之樣品《混合物在2t_7t下保持在攪拌下。 獨製備水冷性維生素（wsv)溶液及抗壞血酸溶液且添 加至經處理之摻合漿料中。藉由在檀拌下向水中添加以下 成分來製備維生素溶液：檸檬酸卸、硫酸亞鐵、WSV預混 物L肉驗、維生素B2、肌醇及核芽酸·膽驗預混物。藉 由將氫氧化卸及抗壞血酸添加至足以溶解該等成分之量的 水中來製備抗壞血酸溶液。接著用氫氧化鉀調節抗壞血酸 溶液pH值至5-9。 用風氧化卸調節摻合物pH值至pH值範圍6 8·7 〇以獲得 最佳產时穩定性。接著標準化摻合物經無菌處理器接受第 二次熱處理。摻合物預加熱至63。(：-74它且在200 psig下均 質化。摻合物進-步加熱至1411144。。且通過固持管。冷 部加熱之摻合物以使溫度降至74t_85Ct且接著在12觀〇〇 PSlg下均質化。進一步冷卻摻合物至16。(：-27。(：且接著在 21C下無菌填充入合適容器中。 實例12-15 在等貫例中’製冑具有高或低微量營養素含量之粉末 第1-2天嬰兒配方及第3_9天嬰兒配方。用於製備配方之成 分闡述於以下表4中。 I61200.doc •77· 201233333 表4 配方12 (第1-2天） 配方13 (第1-2天） 配方14 (第3-9天） 配方15 (第3-9天） Kcal/L 270 250 406 420 營養物含量 低 低 高 成分 單位 每1000 kg批次含量 乳糖 kg 376.90 288.6 406.4 380.4 脫脂乳粉 kg 223.00 223.1 201.1 201.1 高油酸紅花子油 kg 109.30 108.5 97.69 97.7 半乳寡醣 kg 81.70 84.7 104.1 104.10 大豆油 kg 81.70 82.4 74.21 74.2 椰子油 kg 75.30 75.9 68.36 68.4 乳清蛋白濃縮物 kg 48.80 54.9 49.50 49.5 檸檬酸鉀 kg 8.52 42.6 11.12 22.0 ARA油 kg 7.20 7.43 4.643 4.57 乳清蛋白水解產物 kg 6.80 — ___ ——· 碳酸鈣 kg 3.76 ___ 2.839 1.5 磷酸三鈣 kg — 24.1 2.638 10.9 DHA油 kg 2.70 2.8 1.752 1.7 抗壞血酸 kg 2.03 3.20 2.006 2.0 核苷酸-膽鹼預混物 kg 2.01 5.9 2.346 3.6 氣化鉀 kg 1.154 — 1.219 ——· 維生素/礦物質/牛磺酸 預混物 kg 1.116 2.8 1.116 1.7 牛磺酸 g 341 859.9 341 528.9 m-肌醇 g 248 624.3 248 384.0 硫酸辞 g 114 287.9 114 177.1 菸鹼醯胺 g 72.8 183.5 72.8 112.9 泛酸鈣 g 43.7 110 43.7 67.7 硫酸亞鐵 8 38.2 96.3 38.2 59.2 硫酸銅 g 13.4 33.8 13.4 20.8 鹽酸維生素B1 g 11.3 28.5 11.3 17.5 維生素B2 g 4.98 12.60 4.98 7.72 161200.doc -78 * 201233333 配方12 (第1-2天） 配方13 (第1-2天） 配方14 (第3-9天） 配方15 (第3-9天） 鹽酸維生素B6 g 4.58 11.5 4.58 7.07 葉酸 g 1.53 3.9 1.53 2.4 硫酸猛· g 1.3 3.27 1.3 2.01 生物素 mg 441 1100 441 683 砸酸鈉 mg 264 666.1 264 410 氰鈷胺素 mg 35.1 88.6 35.1 54.5 大豆卵磷脂 kg 1.120 1.1 1.112 1.1 氯化鎂 kg 0.839 6.6 1.437 3.4 氯化鉀 kg ___ 2.6 ___ 2.3 棕櫚酸抗壞血酸酯 g 459.25 348.1 313.5 313.6 類胡蘿«素預混物 8 454.02 463.0 286.6 286.6 番茄紅素 g 2.27 2.27 1.43 1.41 葉黃素 mg 953 953 602 589.9 β-胡蘿蔔素 mg 499 499 315 308.9 硫酸亞鐵 § 453.5 1100 453.6 703.1 氯化膽驗 g 432.1 1100 432.1 670.2 氣化納 g 388.0 7100 1138 2900 維生素A、D3、Ε、Κ1 § 385.24 914.5 327.3 568.8 RRR乙酸α-生育酚 g 77.9 184.9 66.2 115.0 棕橺酸維生素A g 14.63 34.7 12.4 21.6 維生素K1 mg 847 2000 720 1250 維生素D3 mg 102.3 243.5 87.1 151.4 混合生育酚 g 246.3 153.4 138.2 138.2 L-肉驗 g 26.3 66.3 23.3 40.8 維生素B2 g 3.2 8.0 3.2 4.9 1 N氫氧化鉀 視需要 視需要 視需要 視需要 藉由製備至少兩種獨立漿料，接著使其摻合在一起，熱 處理，標準化，第二次熱處理，蒸發以移除水且最終喷霧 乾燥來製備配方。最初，藉由使所選碳水化合物（例如乳 16I200.doc •79· 201233333 糖、半乳寡醣）在60°C-71°C下溶解於水中，接著添加氣化 鎂、氯化鉀、檸檬酸鉀 '氣化膽鹼及氯化鈉（礦物質視調 配物而不同）來製備碳水化合物-礦物質装料。所得喂料在 49°C -60°C下保持在適度攪拌下直至其隨後與其他製備之衆 料摻合在一起。 藉由在49°C-60°C下合併高油酸紅花子油、大豆油及挪子 油’接著添加棕摘酸抗壞血酸醋、混合生育齡、大豆印碟 脂、油溶性維生素預混物、乳清蛋白濃縮物、乳清蛋白水 解產物（在一些情況下）、類胡蘿蔔素預混物及碳酸弼（及/ 或磷酸三鈣）來製備油包蛋白質漿料。所得油漿料在38&lt;^· 49°C下保持在適度攪拌下直至其隨後與其他製備之漿料摻 合在一起。 在充分攪拌下合併水、碳水化合物-礦物質漿料、脫脂 乳及油包蛋白質漿料。用氫氧化鉀調節所得摻合物之pH 值。該摻合物在49t：-60°C下保持在適度攪拌下。在？11值 調節後且加工之前添加ARA油及DHA油。 加熱所得摻合物至71。匚_77。(：，經單階段均質器乳化至最 高值300 psig且接著加熱至82〇c_88t：保持約5秒。加熱之摻 合物通過快速冷卻器以使溫度降至77C»c_82&lt;t，且接著通過 板式冷卻器以使溫度進一步降至71〇c_77〇c。接著冷卻之摻 · 合物在2400·2600/400-600 psig下均質化，保持在74〇c_ 85 C下〗6移且接著冷卻至2它_7。(：。獲取用於分析測試之樣 品。混合物在2°C-7t：下保持在攪拌下。 獨立製備水溶性維生素（WSV)溶液及抗壞血酸溶液且添 161200.doc -80- 201233333 加至經處理之摻合漿料中。藉由在攪拌下向水中添加以下 成分來製備維生素溶液：#檬酸鉀、硫酸亞鐵、wsv預混 物、L-肉鹼、維生素32及核苷酸_膽鹼預混物（特定成分視 調配物而；。#由將|氧化卸及抗壞血酸添加至足以 溶解該等成分之量的水中來製備抗壞血酸溶液^接著用氣 氧化鉀調節抗壞血酸溶液pH值至5-9。 用氫氧化鉀調節摻合物pH值至pH值範圍6 6〇 6 9〇以獲 得最佳產品穩定性。接著標準化摻合物接受第二次熱處 理。最初加熱摻合物至66〇c_82t，且接著進—步加熱至 118 C-124 c保持約5秒。接著加熱之掺合物通過快速冷卻 器以使溫度降至71°C-82t： ^在熱處理後，摻合物蒸發降至 被度 1.15-1.17 g/inL。 蒸發之摻合物通過噴霧乾燥器以達成成品粉末中水分含 量為2.5 /〇之目；^ 〇接著成品粉末與水一起聚結為黏合劑溶 液。接著將成品封裝入合適容器中。 實例16 在此實例中，評估能量含量對嬰兒配方之緩衝能力及緩 衝強度之影響。明確言之，測定本發明之多種第12天嬰 兒配方及第3-9天嬰兒配方之緩衝能力及緩衝強度且與市 售粉末對照嬰兒配方、市售即食型2盎司殺菌釜滅菌對照 嬰兒配方、市售即食型32盎司無菌滅菌對照嬰兒配方及人 乳之緩衝能力及緩衝強度進行比較。用於製備對照配方之 成分闡述於以下表5令。 161200.doc -81 - 201233333 表5 對照配方 1(粉末） 對照配方2(殺菌釜滅菌） 對照配方 3(無菌滅菌） Kcal/L 676 676 676 成分 單位 每1000 kg批次含量 水 kg — Q.S. Q.S. 濃縮脫脂乳 kg 698.5 83.61 86.64 乳糖 kg 386.0 54.88 54.7 高油酸紅花子油 kg 114.4 14.07 14.0 大豆油 kg 85.51 10.54 10.5 椰子油 kg 78.76 10.05 10.0 半乳寡醣 kg 69.50 8.630 8.60 乳清蛋白濃縮物 kg 51.08 6.120 6.52 檸檬酸鉀 g 9168 518.3 418.07 碳酸鈣 g 4054 508.5 477.16 ARA油 β 2949 355.6 378.16 核苷酸-膽鹼預混物 β 2347 293.2 293.26 氣化鉀 g 1295 208.5 282.24 角叉菜膠 8 ___ 175.0 240.00 抗壞血酸 G 1275 727.5 582.12 大豆卵磷脂 G 1120 534.6 356.11 穩定劑 G — 534.6 356.11 維生素/礦物質/牛 磺酸預混物 G 1116 142.8 142.77 牛項酸 G 340.5 43.66 43.654 m-肌醇 G 247.9 31.70 31.695 硫酸鋅 G 114.2 14.62 14.617 菸鹼醯胺 G 72.78 9.323 9.3157 泛酸鈣 G 44.16 5.587 5.5860 硫酸亞鐵 G 39.24 4.880 4.8870 硫酸銅 G 13.68 1.714 1.7143 鹽酸維生素B1 G 11.30 1.445 1.4456 維生素B2 Mg 4985 637.6 637.47 161200.doc ·82· 201233333 對照配方 1(粉末） 對照配方2(殺菌釜滅菌） 對照配方 3(無菌滅菌） 鹽酸維生素B6 Mg 4572 584.1 583.96 葉酸 Mg 1535 196.4 215.72 硫酸錳 Mg 1306 166.3 166.25 生物素 Mg 441.0 56.41 56.390 石西酸納 Mg 261.8 33.82 33.820 氰鈷胺素 Mg 35.17 4.493 4.500 DHA油 G 1113 135.4 130.01 氣化鎂 G 1038 141.5 140.46 氣化納 G 579.4 視需要 視需要 硫酸亞鐵 G 453.6 58.02 58.03 氮化膽鹼 G 432.1 54.02 50.02 維生素A、D3、 E、K1 G 377.2 47.50 44.76 RRR乙酸α-生育 酚 G 76.23 9.604 9.0507 栋櫊酸維生素A G 14.32 1.803 1.6998 維生素K1 Mg 829.3 104.5 98.47 維生素D3 Mg 100.4 12.65 11.92 檸檬酸 G … 29.80 29.77 棕櫊酸抗壞血酸酯 G 361.3 — — 類胡蘿g素預混物 G 350.1 23.80 42.91 番茄紅素 Mg 1720 119.0 214.55 葉黃素 Mg 735 49.98 90.11 β-胡蘿蔔素 Mg 385 26.18 47.201 混合生育酚 G 159.2 一 … 混合生育酚 G 111.4 — — L-肉驗 G 26.30 3.285 3.28 維生素Β2 G 3.181 1.166 1.4994 磷酸三鈣 G 0-5230 12.5 41.89 磷酸二氫鉀 G — 11.01 36.60 棕櫚酸維生素A Mg --- --- 776.16 棕櫊酸維生素A Mg — — 427.19 α生育酚 Mg … — 7.760 161200.doc -83- 201233333 對照配方 1(粉末） 對照配方2(殺菌釜滅菌） 對照配方 3(無菌滅菌） 磷酸氩二鉀 Kg 0-5.23 … 1 NKOH Kg 視需要 1.583 視需要 氫氧化鉀 G 視需要 79.15 視需要 如上文實例12-15中所描述製備對照配方1 ;如上文實例 1-8中所描述製備對照配方2且如上文實例9-11中所描述製 備對照配方3。 測定多種第1-2天即食型（RTF)殺菌釜滅菌或復原粉末配 方及第3-9天RTF殺菌釜滅菌、RTF無菌滅菌或復原粉末配 方之緩衝能力及緩衝強度且與對照配方1-3及人乳之緩衝 能力及緩衝強度進行比較。明確言之，藉由以1分鐘時間 間隔向50 mL各配方（或在粉末配方情況下為復原配方）中 添加0.5 mL 0.10 M HC1之等分試樣來測定配方（或人乳）之 緩衝強度。在添加各等分試樣後量測各配方之pH值。緩衝 強度報導為使50 mL配方之pH值降至3.0所需之0.10 M HC1 毫升量。藉由向100 mL各配方（或在粉末配方情況下為復 原配方）中添加5.00 mmol HC1來測定配方（或人乳）之緩衝 能力。緩衝能力報導為添加HC1後[H+]之增加量。結果展 示於以下表6以及圖1及2中。 表6Approximately 55% to about 80% of the amount of whitening μ M &lt; is included in the infant formula (in terms of unit volume). Reduced infant formula can be formulated on Day 1-2 and/or Day 3_9 with 161200.doc •63- 201233333. The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, a low calorie infant formula (having high or low micronutrient content) having an infant energy content of from about 200 kcal/L to about 360 kcal/L is administered during the first two days of life (eg, 1_2 days formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of about 3 60 kcal/L to less than 600 kcal/L can then be administered on days 3 to 9 after birth (eg, Days 3-9) ). Formulations may be administered on Days 3-9 after the 9th day after birth, or may be administered on a 10th day after birth (including the implementation of a low calorie formula in low calorie infant formula). In one embodiment, the amount of micronutrients included in the formulation may be any of the above amounts. Formulations for administration to infants will generally be administered daily as ingested as above. In another embodiment, the invention relates to inhibiting the gastroesophage of infants Countercurrent Method The method comprises identifying an infant suffering from gastroesophageal reflux and administering to the infant any one or more of the low calorie infant formulas of the present invention. The infant is preferably a neonate. When the eclipse of the esophagus (GER) occurs, the stomach contains The product flows back into the esophagus and out of the mouth, causing nausea, cough and/or vomiting. GER symptoms include cough, vomiting, coughing, irritability, poor eating, bloody stools, and combinations thereof. When GER occurs, the baby may also cough. , screaming or nervous. For the purposes of the present invention, the term "suppressing gastroesophageal reflux" is intended to include treating, preventing, and/or reducing at least one symptom of GER and/or its symptoms. Without wishing to be bound by any particular theory, the low-calorie infant formula of the present invention has a faster gastric emptying rate than the full-calorie formula (ie, the contents pass through the stomach). Rate) 'It causes a decrease in gastroesophageal reflux. * As described above, any of the low calorie infant formulas of the present invention can be used in this method. The low calorie infant formula can have a low micronutrient content or, in some embodiments, can have a high trace amount Nutrient content, and may be a Day 1-2 formulation or a Day 3-9 formulation. In one embodiment, the infant formula has an energy content of from about 200 kcal/L formulation to less than 600 kcal/L formulation. Including two or more different infant formulas administered to the infant. For example, in one embodiment, the infant is administered an energy content of from about 200 kcal/L to about 360 kcal/L during the first two days of life. -2 days formula' and then on the 3rd to 9th day after birth, the 3rd-9th formula with an energy content of about 36〇kcal/L to less than 600kcal/L. It can be cast after the 9th day after birth. Formula with Days 3-9' or available The formulation of a higher calorie formula on the first day of life (including the formulation of a full calorie formula for infants will usually be administered daily as ingested above. In another aspect, the invention relates to a method of inhibiting the reflux of the stomach esophagus in infants) Which comprises administering to the infant one or more of the low micronutrient infant formulas of the invention. The infant is preferably a neonate. The low micronutrient infant formula may be any of the above formulas. The methods may further comprise administering two infants. Or two or more different infant formulas. For example, in one embodiment, a low calorie infant formula having an infant energy content of from about 2 〇〇 kcal/L to about 360 kcal/L during the first two days of life (with High or low micronutrient content) (eg, Day 2 formula). A low-calorie infant formula (with high or low micronutrient content) with an infant energy content of approximately 161200.doc •65-201233333 360 kcal/L to less than 600 kcal/L can then be administered on days 3-9 after birth (eg Formula 3_9 days). The formula may be administered on the 3rd to 9th day after the 9th day after birth, or the topical calorie formula (including the full calorie formula) may be administered on the 1st day after birth. In embodiments where the low calorie infant formula has a low micronutrient content, the amount of micronutrients included in the formula can be any of the above levels. Formulations for infants will usually be administered daily as described above. In another aspect, the invention is directed to a method of increasing the rate of gastric emptying in an infant comprising administering to the infant one or more of the low micronutrient formulas of the invention are preferably neonates. The low micronutrient infant formula can be any of the above formulations. The methods may further comprise administering two or more different infant formulas to the infant. For example, in one embodiment, the infant is administered an energy content of between about 200 kcal/L and about 360 during the first two days of life. Kcal/L low calorie infant formula (with high or low micronutrient content) (eg Day 丨_2 day formula). A low calorie infant formula (with high or low micronutrient content) (e.g., day 3-9 formulation) with an infant energy content of from about 360 kcal/L to less than 600 kcal/L can then be administered on days 3-9 after birth. The formula may be administered on days 3-9 after the ninth day after birth, or the calorie formula (including the full calorie formula) may be administered on the first day after birth. The amount of micronutrients included in the formulation may be any of the above amounts. Formulations for administration to infants will usually be administered daily as described above. In addition, the present invention provides a kit comprising two or more of the low calorie 161200.doc-66 - 201233333 infant formulas of the present invention. For example, in some embodiments, the kit can include at least one i-day formula and at least one day 3-9 formulation. Preferably, the kit will contain a sufficient amount of formula 1-2 to provide adequate nutrition for the baby during the first two days of life, and a sufficient amount of formula 3-9 to provide the infant at least on day 3-9 after birth. nutrition. The infant formula included in the kit can be in any suitable form including, for example, a ready-to-feed liquid, a concentrated liquid, a powder, or a combination thereof. The kit can include low calorie, low micronutrient formulations and/or low calorie, high micronutrient formulations. The kit may further include a kit instruction manual as the case may be. For example, the instructions may describe how to use the formula, for example, indicating that the formulation should be administered on Day 1-2 for the first two days after birth and that the formulation should be administered on Days 3-9 on Days 3-9 after birth. Time course; and/or can describe how to practice any of the methods described in this disclosure. The instructions may further describe how to restore any powdered infant formula included in the kit. In addition to the infant formula and optionally instructions, the kit may also include, for example, a plurality of baby bottles of various sizes, a bottle of various sizes, a bottle nipple, and the like. EXAMPLE 1 The following examples illustrate particular embodiments or features of the infant formula and method of the present invention. The examples are provided for illustrative purposes only and are not to be considered as limiting. </ RTI> </ RTI> </ RTI> Various changes are made without departing from the spirit and scope of the invention. Unless otherwise stated, all exemplified amounts are by weight based on the total weight of the composition. 161200.doc -67- 201233333 Sterilization kettle sterilization and aseptic sterilization formulations prepared according to the preparation methods described herein are ready-to-eat liquid formulations, unless otherwise stated. Examples 1-8 In these examples, a 1-2 day infant formula with a high or low micronutrient content and a 3-9 day infant formula were prepared. The ingredients used to prepare the formulations are set forth in Tables 1 and 2 below. Table 1: Day 1-2 Formulation Unit Formula 1 (Day 1-2) Formula 2 (Day 1-2) Formula 3 (Day 1-2) Formula 4 (Day 1-2) Energy Kcal/L 270 270 250 250 Micronutrient content is low and high and the composition (per 1000 Kg batch content) Water kg Appropriate amount of proper amount of lactose kg 23.2 23.1 15.5 15.2 Skim milk powder kg 11.0 11.0 11.0 11.3 galacto-oligosaccharide kg 4.40 4.40 4.40 4.40 high Oleic acid safflower oil kg 5.34 5.35 5.33 5.37 Soybean oil kg 4.00 4.00 3.99 4.00 Coconut oil kg 3.82 3.82 3.81 3.84 Whey protein concentrate kg 2.70 2.70 2.70 2.86 1 NKOH g 1340 1.40 1340 1340 Potassium argon oxide g 67.0 70.0 67.0 67.0 Phosphoric acid Calcium hydrogen g 327.1 249.8 1090 770.2 Potassium citrate g 3.10 1.24 1370 1240 Calcium citrate g 351.0 578.8 752.6 768.9 Ascorbic acid g 727.5 727.5 727.5 727.5 ARA oil g 367.9 367.9 367.9 367.9 Nucleotide-choline premix g 328.5 328.5 328.5 328.5 Dicalcium phosphate g ___ ... • speak ___ magnesium chloride g 16.8 102.6 460.9 450.7 161200.doc -68- 201233333 Unit Formula 1 (Day 1-2) Formula 2 (Day 1-2) Formula 3 (Part 1- 2 days Formulation 4 (Day 1-2) Chlorinated sodium g 45.7 28.5 325.8 186.7 Soy lecithin g 143.0 143.0 143.0 143.0 Post-distilled monoglyceride g 143.0 143.0 143.0 143.0 Vitamin/Mineral/Taurine Premix g 31.4 57.1 157.0 157.0 Taurine g 9.60 17.5 48.0 48.0 m-inositol g 6.97 12.7 34.85 34.85 Zinc sulfate g 3.21 5.85 16.07 16.07 Nicotinamide s 2.05 3.73 10.24 10.24 Calcium pantothenate g 1.23 2.23 6.14 6.14 Ferrous sulfate g 1.07 1.95 5.37 5.37 Copper sulfate mg 377 686 1890 1890 Vitamin B1 mg 318 578 1590 1590 Vitamin B2 mg 140 255 701 701 Vitamin B6 mg 128 234 642 642 Folic acid mg 43.2 78.5 216 216 Manganese sulfate mg 36.6 66.5 183 183 Biotin mg 12.4 22.6 62.0 62.0 sodium acidity sodium 7.44 13.5 37 37 cyanocobalamin mg 0.990 1.8 4.95 4.95 DHA oil s 137.9 137.9 137.9 137.9 potassium chloride g 46.3 52.4 as needed 60.7 gasification test g 58.9 21.5 88.9 54.0 ferrous sulfate g 5.80 23.20 60.9 60.9 Carrageenan g 175.0 175.0 175.0 175.0 Vitamin A, D3, E, K1 g 22.8 19.0 47.5 47.5 RRR A-tocopherol g 4.61 3.84 9.6 9.6 Palmitic Acid Vitamin A mg 867 721.5 1800 1800 Vitamin K1 mg 50.2 41.8 104.5 104.5 Vitamin D3 mg 6.08 5.06 12.65 12.65 Citric acid g 29.8 29.8 29.8 29.8 Mixed carotenol premix g 23.8 23.8 23.8 23.8 Tomato red Prime mg 119 119 119 119 161200.doc •69- 201233333 Unit Formula 1 (Day 1-2) Formula 2 (Day 1-2) Formula 3 (Day 1-2) Formula 4 (Day 1-2) Lutein mg 50 50 50 50 β-carotene mg 26.2 26.2 26.2 26.2 Inositol g 33.1 6.6 12.9 12.9 L-meat test g 6.38 1.31 6.38 3.28 Vitamin Β 2 mg — 466.0 882 882 Table 2: Formulations for Days 3-9 Formula 5 (Days 3-9) Formula 6 (Days 3-9) Formulation 7 (Days 3-9) Formulation 8 (Days 3-9) Energy Kcal/L 406 406 406 410 Low levels of micronutrients Ingredients (per 1000 Kg batch content) Water kg Appropriate amount of proper amount of lactose kg 37.0 37.2 37.5 35.50 Skim milk powder kg 16.3 16.2 16.2 16.30 Semi-milk sugar collection kg 8.63 8.63 8.63 8.63 High oleic acid safflower oil kg 7.72 7.72 7.72 7.72 Soybean oil kg 5.78 5.78 5.78 5.78 hazelnut oil kg 5.52 5.52 5.52 5.51 Whey protein concentrate kg 4.00 4.00 4.00 4.00 1NKOH kg 1.34 1.34 0.8035 1.34 Potassium hydroxide g 67.0 67.0 40.2 67.0 Calcium arsenate kg 0.309 ___ ___ — Potassium citrate kg 0.00186 0.00186 0.00186 1.06 Calcium citrate g 687.6 583.5 583.5 261.1 Ascorbic acid g 727.5 727.5 436.5 727.5 ARA oil g 378.2 378.2 378.2 378.2 Nucleotide-choline premix g 319.7 319.7 319.7 319.7 Ultrafine tricalcium phosphate 8 ___ 226.8 226.8 1470 Magnesium oxide g 122.5 147.7 147.7 288.1 Gasification g —— 235.8 161200.doc -70· 201233333 Unit Formula 5 (Days 3-9) Formula 6 (Days 3-9) Formulation 7 (Days 3-9) Formula 8 (Days 3-9) Soybean Eggs Scale gum g 206.0 206.0 206.0 206.0 steamed glycerin monoglycol g 206.0 206.0 206.0 206.0 vitamin / mineral / taurine premix g 85.6 115.7 115.7 142.7 bovine acid g 26.2 35.4 35.4 43.6 m_inositol g 19.0 25.7 25.7 31.7 Zinc sulphate 8 8.76 11.8 11.8 14.61 Nicotine guanamine g 5.59 7.55 7.55 9.31 Calcium pantothenate 8 3.35 4.53 4.53 5.58 Ferrous sulphate g 2.93 3.96 3.96 4.88 Copper sulphate g 1.03 1.39 1.39 1.71 Hydrochloric acid vitamin B1 g 0.8667 1.17 1.17 1.44 Vitamin B2 mg 382.2 516.6 516.6 637 Hydrochloric acid vitamin B6 mg 350.1 473.2 473.2 584 Folic acid mg 117.7 159.1 159.1 196 Manganese sulfate mg 99.7 134.7 134.7 166 Biotin mg 33.8 45.7 45.7 56.0 Citrate nano mg 20.3 27.4 27.4 34 cyanokinin mg 2.7 3.64 3.64 4.5 DHA oil g 137.9 137.9 137.9 137.9 gasified potassium s 108.7 111.3 111.3 129.5 gasified biliary test g 32.4 32.4 32.4 88.9 ferrous sulfate g 34.8 37.5 37.5 60.9 carrageenan g 175.0 175.0 175.0 175.0 Vitamin A, D3, E, K1 g 28.5 30.2 30.2 44.8 RRR Acetate alpha-tocopherol g 5.8 6.11 6.11 9.1 Palmitic acid vitamin AR 1.08 1.15 1.15 1.7 Vitamin K1 mg 62.7 66.4 66.4 98.5 Vitamin D3 mg 7.6 8.04 8.04 11.9 Citric acid g 29.8 29.8 29.8 29.8 Mixed carotenoid premix g 23.8 23.8 23.8 23.8 Lycopene mg 119 119 119 119 Lutein mg 50 50 50 50 161200.doc -71 - 201233333 Unit formula 5 ( 3-9 days) Formulation 6 (Days 3-9) Formulation 7 (Days 3-9) Formulation 8 (Days 3-9) Beta-carotene mg 26.2 26.2 26.2 26 .2 Inositol g ... I-... 12.9 L-Carnitine R 1.97 2.31 2.31 5.51 Vitamin Β 2 g 0.70 0.699 0.699 1.50 Vitamin A mg ... 770 770 780 Palmitic acid A mg 420 420 425 Sulfuric acid steel Mg --- - 391 Formulations were prepared by preparing at least two separate slurries, then blending them together, heat treating 'normalized and terminally sterilized. Initially, by dissolving selected carbohydrates (eg, lactose, galactooligosaccharides) in water at 74 ° C -79 ° C 'then adding citric acid, magnesium hydride, potassium hydride, potassium citrate, gas The chemistry and gasification of sodium are used to prepare a carbohydrate-mineral slurry. The resulting slurry was maintained under moderate agitation at 49 ° C - 60 ° C until it was subsequently blended with other prepared ingredients. High oleic safflower oil, coconut oil, monoglyceride and soy lecithin were combined by heating and heated to 66 ° C -79. (: to prepare oil-packed protein stimulating material. After standing for 10-15 minutes) then add soybean oil, oil-soluble vitamin premix, mixed catechol premix, carrageenan, Vitamin A, citric acid, citric acid, ARA oil, DHA oil and whey protein concentrate. The resulting oil slurry is kept at 49 ° C -60. (: kept under moderate agitation until it is subsequently prepared with other preparations The slurry is blended together. The water is heated to 49 ° C -60 ° C and then combined with the carbohydrate_mineral slurry, skim milk and oil-in-oil slurry with sufficient agitation. pH of the compound. The blend was kept under moderate agitation at 49t: _6 (rc. 161200.doc • 72· 201233333) The obtained blend was heated to 74 ° C -79 ° C and emulsified by a single-stage homogenizer. To 900-1100 psig and then heated to 144. 〇 _147. 〇 is held for about $ seconds. The heated handle is passed through a flash cooler to bring the temperature down to 88 〇 c_93 &lt; 5c, and then passed through a plate cooler to bring the temperature Further reduced to 74. 〇85. (:. Then the cooled blend was at 2900·3100/400-600 psig Qualification, kept at 74 C-85 C for 16 seconds and then cooled to 2 〇C-7t: Obtain a sample for analytical testing. The mixture is at 2. (: -7. (: keep under stirring. Independent A water-soluble vitamin (WSV) solution and an ascorbic acid solution are prepared and added to the treated blended slurry. The vitamin solution is prepared by adding the following ingredients to the water under stirring: potassium citrate, ferrous sulfate, wsv premix , L-carnitine, copper sulfate, vitamins, inositols, and nucleotides-preparation/preparation of anti-bad money solutions by adding hydroxide and ascorbic acid to an amount sufficient to dissolve the components. Then adjust the pH of the ascorbic acid solution to 5-9 with hydrogen peroxide. Adjust the pH of the blend with potassium hydroxide to the pH range of 71_7 6 (depending on the product) to obtain the best product properties. Then the finished product Filled into a suitable container and finally sterilized.Examples 9-11 In these examples, 32 sterile sterilized 3-9 day infant formulas with high or low micronutrient content were prepared. See Table 3 below. J61200.doc -73- 2012333 33 Table 3 Unit Formulation 9 (Days 3-9) Formulation 10 (Days 3-9) Formulation 11 (Days 3-9) Energy Kcal/L 406 410 410 Low Micronutrient Content 13⁄4 High Composition Per 1000 kg Batch Containing 3 water kg Appropriate amount of proper amount of lactose kg 37.0 33.7 34.03 skim milk powder kg 16.3 17.0 16.47 galacto-oligosaccharide kg 8.63 8.63 8.63 high oleic acid safflower oil kg 7.72 7.83 7.72 soybean oil kg 5.78 5.87 5.78 coconut oil kg 5.52 5.60 5.51 milk Albumin concentrate kg 4.00 4.19 4.05 1ΝΚΟΗ kg 1.85 1.85 1.85 Potassium hydroxide 8 92.5 92.5 92.5 Calcium citrate g 675.0 716.8 993.9 Calcium hydrogen phosphate g 577.4 1170 1390 Ascorbic acid g 431.7 431.7 431.7 ARA oil g 378.2 378.2 378.2 Nucleotide-biliary Alkali premix g 319.7 319.7 319.7 Soy lecithin g 206.0 206.0 206.0 Diglyceride after distillation 8 206.0 206.0 206.0 Carrageenan g 200.0 240.0 200.0 DHA oil R 137.9 137.9 137.9 Magnesium oxide g 128.9 279.3 285.9 Potassium sulphate g 118.5 213.9 122.4 gasification test g 88.9 54.0 88.9 vitamin / mineral / taurine premix g 41.4 142.7 142.7 bovine acid g 12.7 43.6 43.6 M-inositol g 9.19 31.7 31.7 Zinc sulfate g 4.24 14.61 14.61 161200.doc ·74· 201233333 Unit formulation 9 (days 3-9) Formulation 10 (days 3-9) Formulation 11 (days 3-9) Amine amine g 2.70 9.31 9.31 Calcium pantotheitate g 1.62 5.58 5.58 Ferrous sulfate g 1.42 4.88 4.88 Copper sulfate mg 497 1710 1710 Hydrochloric acid vitamin B1 mg 419 1440 1440 Vitamin B2 mg 185 637 637 Hydrochloric acid vitamin B6 mg 169 584 584 Folic acid mg 56.9 196 196 Manganese sulfate mg 48.2 166 166 Biotin mg 16.4 56.0 56.0 Sodium citrate mg 9.81 34 34 Cyanocobalamin mg 1.3 4.5 4.5 Chlorinated sodium g 32.1 65.4 231.9 Vitamin A, D3, E, K1 g 30.9 44.8 44.8 - Tocopherol g 6.24 9.1 9.1 Palmitic acid vitamin AS 1.17 1.7 1.7 Vitamin K1 mg 67.9 98.5 98.5 Vitamin D3 mg 8.22 11.9 11.9 Citric acid g 29.8 29.8 29.8 Inositol 8 25.8 12.9 12.9 Mixed carotenoid premix g 23.8 23.8 23.8 Lycopene mg 119 119 119 Lutein mg 50 50 50 β-carotene mg 26.2 26.2 26.2 Ferrous sulfate g 16.2 60.9 60.9 L-meat test g 5.51 3.28 5.51 Potassium citrate g 3.10 895.0 1060 dimension Β2 mg 599 1500 1500 Vitamin A mg ___ 780 780 Palmitic acid vitamin A mg ___ 425 425 Copper sulphate mg — —— 391 By preparing at least two separate slurries, then blending them together, heat 161200.doc • 75- 201233333 The treatment was prepared by quantification followed by aseptic processing and filling. Most: C: The selected carbohydrates (such as lactose, galacto-oligosaccharides) are read in water at 1 ^, followed by (4) citric acid, chlorine reduction, gasification unloading, potassium, gasification, and gasification. (Mineral varies depending on the formulation). The slurry obtained from 1 H mineral f slurry is kept under moderate agitation at machine-6〇t:5 until it is subsequently blended with other prepared slurry. High oleic safflower oil, coconut oil, monoglyceride s and large ugly lecithin were combined by heating and heated to 66. . _79. After preparing the oil-packed protein slurry for 10 1 5 minutes, the soybean oil, the oil-bathed vitamin premix, the mixed carotenoid premix, and the viniferine glutinous rice glutinous rice glutinous rice are added to the granule. Calcium, calcium hydrogen phosphate, ARA oil, dha oil and whey protein concentrate. The resulting oil slurry was maintained under moderate mixing under machine-to-machine until it was subsequently blended with other prepared slurries. The water is heated to 491-6 〇t and then combined with the carbohydrate_mineral slurry, skim milk and oil-in-oil protein rejects with sufficient agitation. The {^ value of the resulting blend was adjusted by dehydration with hydrogen. The blend was kept under moderate agitation at 49t: 6〇t:. The resulting blend was heated to 74 t -79 ° C, emulsified to 900-1100 psig via a single stage homogenizer and then heated to 144 tM 4 rc for about $ seconds. The heated blend was passed through a flash cooler to bring the temperature down to 88 t &gt; c_93 〇 c and then passed through a plate cooler to further reduce the temperature to 74. 〇85. (: The subsequently cooled blend was homogenized at 2900-3100/400-600 psig, held at 74 °C - 85 °C for 16 seconds and then cooled to 2 °C - 7t. Obtained for analysis of 161200 .doc -76- 201233333 Test sample "The mixture is kept under stirring at 2t_7t. A water-cooled vitamin (wsv) solution and ascorbic acid solution are prepared separately and added to the treated blended slurry. The following ingredients are added to the water to prepare a vitamin solution: citric acid unloading, ferrous sulfate, WSV premix L meat test, vitamin B2, inositol and nucleotate-bone test premix. By adding hydroxide to the ascorbic acid The ascorbic acid solution is prepared in an amount sufficient to dissolve the components. The pH of the ascorbic acid solution is adjusted to 5-9 with potassium hydroxide. The pH of the blend is adjusted to a pH range of 6 8·7 by aerobic oxidation. The best time stability was obtained. The standardized blend was then subjected to a second heat treatment by a sterile processor. The blend was preheated to 63. (: -74 and it was homogenized at 200 psig. Heated to 1411144. and through the holding tube. The composition was allowed to homogenize to a temperature of 74t to 85 Ct and then at 12 guans PS lg. The blend was further cooled to 16. (: -27. (and then subsequently aseptically filled into a suitable container at 21 C. Example 12 - 15 In the case of coherence, prepare infant formulas with high or low micronutrient content, Day 1-2 infant formula and Day 3-9 infant formula. The ingredients used to prepare the formulation are described in Table 4 below. I61200.doc •77 · 201233333 Table 4 Formulation 12 (Day 1-2) Formulation 13 (Day 1-2) Formulation 14 (Days 3-9) Formulation 15 (Days 3-9) Kcal/L 270 250 406 420 Nutrient Content Low low and high component units per 1000 kg batch content lactose kg 376.90 288.6 406.4 380.4 skim milk powder kg 223.00 223.1 201.1 201.1 high oleic acid safflower oil kg 109.30 108.5 97.69 97.7 galacto-oligosaccharide kg 81.70 84.7 104.1 104.10 soybean oil kg 81.70 82.4 74.21 74.2 Coconut oil kg 75.30 75.9 68.36 68.4 Whey protein concentrate kg 48.80 54.9 49.50 49.5 Potassium citrate kg 8.52 42.6 11.12 22.0 ARA oil kg 7.20 7.43 4.643 4.57 Whey protein hydrolysate kg 6.80 — ___ ——· Carbonated Kg 3.76 ___ 2.839 1.5 Tricalcium phosphate kg — 24.1 2.638 10.9 DHA oil kg 2.70 2.8 1.752 1.7 Ascorbic acid kg 2.03 3.20 2.006 2.0 Nucleotide-choline premix kg 2.01 5.9 2.346 3.6 Calcium carbonate kg 1.154 — 1.219 —— Vitamin/Mineral/Taurine Premix kg 1.116 2.8 1.116 1.7 Taurine g 341 859.9 341 528.9 m-inositol g 248 624.3 248 384.0 Sulfuric acid g 114 287.9 114 177.1 Nicotine guanamine g 72.8 183.5 72.8 112.9 Pantothenic acid Calcium g 43.7 110 43.7 67.7 Ferrous sulfate 8 38.2 96.3 38.2 59.2 Copper sulfate g 13.4 33.8 13.4 20.8 Hydrochloric acid vitamin B1 g 11.3 28.5 11.3 17.5 Vitamin B2 g 4.98 12.60 4.98 7.72 161200.doc -78 * 201233333 Formula 12 (第1-2 Day) Formulation 13 (Day 1-2) Formulation 14 (Days 3-9) Formulation 15 (Days 3-9) Vitamin B6 g 4.58 11.5 4.58 7.07 Folic acid g 1.53 3.9 1.53 2.4 Sulfuric acid fi · g 1.3 3.27 1.3 2.01 Biotin mg 441 1100 441 683 Sodium citrate mg 264 666.1 264 410 Cyanocobalamin mg 35.1 88.6 35.1 54.5 Soy lecithin kg 1.120 1.1 1.112 1.1 Magnesium chloride kg 0.839 6.6 1.437 3.4 Potassium chloride Kg ___ 2.6 ___ 2.3 Ascorbyl palmitate g 459.25 348.1 313.5 313.6 Carotenoids prime premix 8 454.02 463.0 286.6 286.6 Lycopene g 2.27 2.27 1.43 1.41 Lutein mg 953 953 602 589.9 Beta-carotene mg 499 499 315 308.9 Ferrous sulfate § 453.5 1100 453.6 703.1 Chloride test g 432.1 1100 432.1 670.2 Gasification nano g 388.0 7100 1138 2900 Vitamin A, D3, Ε, Κ1 § 385.24 914.5 327.3 568.8 RRR A-tocopherol acetate 77.9 184.9 66.2 115.0 Palmitic acid vitamin A g 14.63 34.7 12.4 21.6 Vitamin K1 mg 847 2000 720 1250 Vitamin D3 mg 102.3 243.5 87.1 151.4 Mixed tocopherol g 246.3 153.4 138.2 138.2 L-meat test g 26.3 66.3 23.3 40.8 Vitamin B2 g 3.2 8.0 3.2 4.9 1 N-potassium hydroxide can be prepared as needed by preparing at least two separate slurries as needed, then blending them together, heat treatment, normalization, second heat treatment, evaporation to remove water and finally spray drying. Prepare the formula. Initially, by dissolving selected carbohydrates (eg, milk 16I200.doc •79·201233333 sugar, galactooligosaccharide) in water at 60°C-71°C, then adding magnesium sulfate, potassium chloride, lemon Potassium acid 'gasification choline and sodium chloride (mineal depending on the formulation) to prepare a carbohydrate-mineral charge. The resulting feed was maintained at 49 ° C - 60 ° C with moderate agitation until it was subsequently blended with other prepared ingredients. By combining high oleic safflower oil, soybean oil and raspberry oil at 49 ° C - 60 ° C, followed by adding palm acid pickic acid ascorbic acid vinegar, mixed age, soybean printing fat, oil soluble vitamin premix, A whey protein concentrate, a whey protein hydrolysate (in some cases), a carotenoid premix, and cesium carbonate (and/or tricalcium phosphate) are used to prepare a protein-packed protein slurry. The resulting oil slurry was kept under moderate agitation at 38 &lt; ^ 49 ° C until it was subsequently blended with other prepared slurries. The water, carbohydrate-mineral slurry, skim milk and oil-in-oil slurry were combined with sufficient agitation. The pH of the resulting blend was adjusted with potassium hydroxide. The blend was kept under moderate agitation at 49t: -60 °C. in? 11 values were adjusted and ARA oil and DHA oil were added before processing. The resulting blend was heated to 71.匚_77. (:, emulsified to a maximum of 300 psig via a single stage homogenizer and then heated to 82 〇c_88t: held for about 5 seconds. The heated blend was passed through a flash cooler to bring the temperature down to 77C»c_82&lt;t, and then passed The plate cooler was used to further reduce the temperature to 71 〇 c_77 〇 c. The cooled admixture was then homogenized at 2400·2600/400-600 psig, held at 74 〇c_85 C, and then cooled to 2 It _7. (:. Obtain the sample for the analytical test. The mixture is kept under stirring at 2 ° C - 7 t: Separate preparation of water-soluble vitamin (WSV) solution and ascorbic acid solution and add 161200.doc -80- 201233333 Add to the treated blended slurry. Prepare the vitamin solution by adding the following ingredients to the water under stirring: #钾钾, ferrous sulfate, wsv premix, L-carnitine, vitamin 32 and core Glycolate-choline premix (specific component depending on the formulation; ######################################################################################################### Value to 5-9. Adjusting the blend with potassium hydroxide The pH of the compound is adjusted to a pH range of 6 6 〇 6 9 〇 to obtain the best product stability. The normalized blend is then subjected to a second heat treatment. The blend is initially heated to 66 〇 c_82 t, and then heated further to 118 C-124 c is held for about 5 seconds. The heated blend is then passed through a flash cooler to reduce the temperature to 71 ° C - 82 t: ^ After heat treatment, the blend evaporates to a degree of 1.15 - 1.17 g / inL The evaporated blend is passed through a spray dryer to achieve a moisture content of 2.5 / 〇 in the finished powder; ^ 成品 the finished powder is coalesced together with water into a binder solution. The finished product is then packaged into a suitable container. In this example, the effect of energy content on the buffering capacity and buffer strength of the infant formula is evaluated. Specifically, the buffering capacity and cushioning strength of the various 12th day infant formulas of the present invention and the 3-9 day infant formula are determined and Comparison of commercially available powdered control infant formula, commercially available ready-to-eat 2 ounce sterilized control infant formula, commercially available ready-to-eat 32 ounce sterile sterile control infant formula, and human milk buffering capacity and buffer strength. The ingredients of the formula are set out in Table 5 below. 161200.doc -81 - 201233333 Table 5 Control Formula 1 (Powder) Control Formula 2 (Sterilization Sterilization) Control Formula 3 (sterile sterilization) Kcal/L 676 676 676 Ingredient per 1000 kg batch content water kg — QSQS concentrated skim milk kg 698.5 83.61 86.64 lactose kg 386.0 54.88 54.7 high oleic acid safflower oil kg 114.4 14.07 14.0 soybean oil kg 85.51 10.54 10.5 coconut oil kg 78.76 10.05 10.0 galacto-oligosaccharide kg 69.50 8.630 8.60 Whey protein concentrate kg 51.08 6.120 6.52 Potassium citrate g 9168 518.3 418.07 Calcium carbonate g 4054 508.5 477.16 ARA oil β 2949 355.6 378.16 Nucleotide-choline premix β 2347 293.2 293.26 Gasification potassium g 1295 208.5 282.24 Corner Fork Gum 8 ___ 175.0 240.00 Ascorbic acid G 1275 727.5 582.12 Soy lecithin G 1120 534.6 356.11 Stabilizer G — 534.6 356.11 Vitamin/Mineral/Taurine Premix G 1116 142.8 142.77 Bovine acid G 340.5 43.66 43.654 m-muscle Alcohol G 247.9 31.70 31.695 Zinc sulfate G 114.2 14.62 14.617 Nicotinamide G 72.78 9.323 9.3157 Pan Calcium G 44.16 5.587 5.5860 Ferrous sulfate G 39.24 4.880 4.8870 Copper sulfate G 13.68 1.714 1.7143 Vitamin B1 G 11.30 1.445 1.4456 Vitamin B2 Mg 4985 637.6 637.47 161200.doc ·82· 201233333 Control Formula 1 (Powder) Control Formula 2 (Sterilizer) Sterilization) Control Formula 3 (sterile sterilization) Vitamin B6 Mg 4572 584.1 583.96 Folic acid Mg 1535 196.4 215.72 Manganese sulfate Mg 1306 166.3 166.25 Biotin Mg 441.0 56.41 56.390 Stalin sodium Mg 261.8 33.82 33.820 Cyanocobalamin Mg 35.17 4.493 4.500 DHA Oil G 1113 135.4 130.01 Magnesium oxide G 1038 141.5 140.46 Gasification nano G 579.4 If necessary, ferrous sulfate G 453.6 58.02 58.03 Choline nitrite G 432.1 54.02 50.02 Vitamin A, D3, E, K1 G 377.2 47.50 44.76 Α-tocopherol G 76.23 9.604 9.0507 citrate vitamin AG 14.32 1.803 1.6998 Vitamin K1 Mg 829.3 104.5 98.47 Vitamin D3 Mg 100.4 12.65 11.92 Citric acid G ... 29.80 29.77 Palmitic acid ascorbate G 361.3 — — Carotenoids premixed G 350.1 23.80 42.91 Lycopene Mg 1720 119.0 214.55 Lutein Mg 735 49.98 90.11 β-carotene Mg 385 26.18 47.201 Mixed tocopherol G 159.2 a... Mixed tocopherol G 111.4 — L- meat test G 26.30 3.285 3.28 Vitamin Β 2 G 3.181 1.166 1.4994 Tricalcium phosphate G 0- 5230 12.5 41.89 Potassium dihydrogen phosphate G — 11.01 36.60 Vitamin A of palmitic acid Mg --- --- 776.16 Vitamin A of palmitic acid Mg — — 427.19 α tocopherol Mg ... — 7.760 161200.doc -83- 201233333 Control Formula 1 ( Powder) Control Formula 2 (Sterilization Sterilization) Control Formula 3 (sterile sterilization) Dipotassium Phosphate Kg 0-5.23 ... 1 NKOH Kg 1.583 as needed Depending on the need, Potassium G, as needed, 79.15 as required in Examples 12-15 above Control Formulation 1 was prepared as described; Control Formulation 2 was prepared as described in Examples 1-8 above and Control Formulation 3 was prepared as described in Examples 9-11 above. Determination of the buffering capacity and buffering strength of a variety of Day 1-2 ready-to-eat (RTF) Sterilization Sterilization or Reconstituted Powder Formulations and Day 3-9 RTF Sterilization, RTF Sterile or Reconstituted Powder Formulations and Control Formulations 1-3 And the buffer capacity and buffer strength of human milk are compared. Specifically, the buffer strength of the formulation (or human milk) was determined by adding 0.5 mL of an aliquot of 0.10 M HC1 to 50 mL of each formulation (or a reconstituted formulation in the case of a powder formulation) at 1 minute intervals. . The pH of each formulation was measured after each aliquot was added. Buffer strength is reported as the amount of 0.10 M HC1 mL required to reduce the pH of the 50 mL formulation to 3.0. The buffering capacity of the formulation (or human milk) was determined by adding 5.00 mmol of HCl to 100 mL of each formulation (or a reconstituted formulation in the case of a powder formulation). The buffering capacity is reported as the increase in [H+] after the addition of HC1. The results are shown in Table 6 below and Figures 1 and 2. Table 6

配方 能量(kcal/L) 形式 緩衝強度4* 緩衝能力6 對照配方1 676 粉末a 25.8 0.776 mM 配方14(第3-9天） 406 粉末b 17.1 9.55 mM 配方14(第3-9天)e 406 粉末b 17.0 9.33 mM 配方12(第1-2天） 270 粉末b 11.4 20.0 mM 161200.doc •84· 201233333Formula Energy (kcal/L) Form Buffer Strength 4* Buffer Capacity 6 Control Formula 1 676 Powder a 25.8 0.776 mM Formulation 14 (Days 3-9) 406 Powder b 17.1 9.55 mM Formulation 14 (Days 3-9) e 406 Powder b 17.0 9.33 mM Formulation 12 (Day 1-2) 270 Powder b 11.4 20.0 mM 161200.doc •84· 201233333

配方 能量(kcal/L) 形式 緩衝強度*1 緩衝能力6 對照配方2 676 殺菌爸滅菌 25.1 0.977 mM 配方5(第3-9天） 406 殺菌釜滅菌 16.8 7.94 mM 配方5(第3-9天)e 406 殺菌爸滅菌 16.2 9.12 mM 配方2(第1-2天） 270 殺菌爸滅菌 13.2 13.2 mM 配方2(第1-2天)e 270 殺菌爸滅菌 11.9 17.8 mM 配方U第1-2天） 270 殺菌爸滅菌 10.8 18.6 mM 對照配方3 676 無菌滅菌 23.3 L86 mM 配方9(第3-9天） 406 無菌滅菌 16.1 10.5 mM 人乳 11.6 14.1 mM a在測定缓衝能力及緩衝強度前，使用35.0 g配方加240 mL水復原對照配方1。 b在測定緩衝能力及緩衝強度前，分別使用12.2 g配方及 21.4 g配方，加240 mL水復原配方12及14。 c配方2、5及14測試兩次。 d使5〇11^配方之pH值降至3.0所需之0.10MHC1毫升量。 6向100 mL配方中添加5.00 mmol HC1後[H+]之增加量。 如可自該等結果可見，調配物之緩衝能力隨能量含量降 低而降低。能量含量為270 kcal/L之第1·2天配方之缓衝能 力在所有測試配方中最低。已報導人乳之緩衝強度在9.0 至18.0範圍内’平均為13.5 »如可自表6以及圖1及2中闡述 之結果可見，第1 -2天配方之緩衝強度與所測試人乳之緩 衝強度相當或低於所測試人乳之緩衝強度。 本發明之配方’且尤其第1 -2天配方之降低之緩衝能力 及緩衝強度可向嬰兒提供生理學效益。詳言之，緩衝能力 161200.doc • 85 · 201233333 及強度降低可幫助實現更有利的腸道微生物群落分佈且可 增加使經口攝取之腸病原體失活之有效性。 實例17 在此實例中’評估能量含量對嬰兒配方之緩衝能力及緩 衝強度之影響》明確言之’測定本發明之第1 _2天（配方13) 及第3-9天（配方15)粉末嬰兒配方在復原後之緩衝能力及緩 衝強度且與市售粉末對照嬰兒配方（對照配方丨）在復原後之 緩衝能力及緩衝強度進行比較。 使用12.2 g配方加240 mL水復原配方13，使用21.4 g配 方加240 mL水復原配方15且使用35.0 g配方加240 mL水復 原對照配方1。測定各配方之緩衝能力及緩衝強度。明確 言之’藉由以1分鐘時間間隔向100 mL復原配方中添加 1.00 mL 0.500 M HC1之等分試樣來測定配方之緩衝強度。 在添加各等分試樣後量測各配方之pH值。緩衝強度報導為 使100 mL復原配方之pH值自6.00降至3.00所需HC1之毫莫 耳量。藉由向1〇〇 mL各復原配方中添加5.50 mmol HC1來 測定配方之緩衝能力。緩衝能力報導為添加HC1後[H+]之 增加量及添加HC1後pH值降低量。結果展示於以下表7以 及圖3-6中。 表7Formula Energy (kcal/L) Form Buffer Strength*1 Buffering Capacity 6 Control Formulation 2 676 Sterilization Dad Sterilization 25.1 0.977 mM Formulation 5 (Days 3-9) 406 Sterilization Sterilization 16.8 7.94 mM Formulation 5 (Days 3-9) e 406 Sterilization Dad Sterilization 16.2 9.12 mM Formulation 2 (Day 1-2) 270 Sterilization Dad Sterilization 13.2 13.2 mM Formulation 2 (Day 1-2) e 270 Sterilization Dad Sterilization 11.9 17.8 mM Formula U Day 1-2) 270 Sterilization Dad Sterilization 10.8 18.6 mM Control Formulation 3 676 Sterile Sterilization 23.3 L86 mM Formulation 9 (Days 3-9) 406 Sterile Sterilization 16.1 10.5 mM Human Milk 11.6 14.1 mM a Before determining buffer capacity and buffer strength, use 35.0 g formula Control Formulation 1 was reconstituted with 240 mL of water. b Before formulating buffer capacity and buffer strength, use 12.2 g formula and 21.4 g formula, and add 240 mL water to restore formulas 12 and 14. c Formula 2, 5 and 14 were tested twice. d The pH of the 5〇11^ formulation was reduced to the amount of 0.10 MHC 1 ml required for 3.0. 6 Add the amount of [H+] after adding 5.00 mmol of HC1 to the 100 mL formulation. As can be seen from these results, the buffering capacity of the formulation decreases as the energy content decreases. The buffer capacity of the 1st and 2nd day formulations with an energy content of 270 kcal/L was lowest in all test formulations. It has been reported that the buffer strength of human milk is in the range of 9.0 to 18.0 'average 13.5». As can be seen from the results in Table 6 and Figures 1 and 2, the buffer strength of the first 1-2 day formula and the buffer of the tested human milk The strength is equivalent to or lower than the buffer strength of the human milk tested. The reduced buffering capacity and cushioning strength of the formulation of the present invention&apos; and especially the first 1-2 day formulation can provide physiological benefits to the infant. In particular, buffering capacity 161200.doc • 85 · 201233333 and reduced intensity can help achieve a more favorable distribution of intestinal microflora and increase the effectiveness of inactivation of orally ingested intestinal pathogens. Example 17 In this example, 'Evaluating the Effect of Energy Content on Buffering Capacity and Buffering Strength of Infant Formulations' clearly states 'measured on Days 1 to 2 (Formulation 13) and Days 3-9 (Formulation 15) powder infants of the present invention The buffer capacity and buffer strength of the formula after recovery were compared with the buffer capacity and buffer strength of the commercially available powder control infant formula (control formula) after recovery. Formulation 13 was reconstituted using 12.2 g of formula plus 240 mL of water, Formulation 15 was reconstituted using 21.4 g of Formulation plus 240 mL of water and Formulation 1 was reconstituted using 35.0 g of Formula plus 240 mL of water. The buffering capacity and buffering strength of each formulation were determined. Specifically, the buffer strength of the formulation was determined by adding 1.00 mL of an aliquot of 0.500 M HC1 to a 100 mL recovery formulation at 1 minute intervals. The pH of each formulation was measured after each aliquot was added. The buffer strength is reported as the millimolar amount of HC1 required to reduce the pH of the 100 mL recovery formulation from 6.00 to 3.00. The buffering capacity of the formulation was determined by adding 5.50 mmol HCl to each of the 1 〇〇 mL recovery formulations. The buffering capacity is reported as the amount of increase in [H+] after the addition of HC1 and the amount of pH reduction after the addition of HC1. The results are shown in Table 7 below and in Figures 3-6. Table 7

配方13(第1·2天） 配方15(第3-9天） 對照配方1 Kcal/L 250 420 676 緩衝強度immol) 3.41 3.81 4.56 緩衝能力-pH降低量 4.84 4.52 4.02 緩衝能力-丨H+1增加董 6.17 mM 4.17mM 1.20 mM 161200.doc • 86 · 201233333 如可自表7及圖3-6中闡述之結果可見，第1-2天配方及 第3-9天配方之緩衝強度及缓衝能力（如由pH值降低量及 [H+]增加量量測）均顯著低於對照配方之緩衝強度及缓衝 能力。能量含量為250 kcal/L之第1-2天配方在所有測試配 方中缓衝能力及緩衝強度最低，顯示緩衝強度及緩衝能力 隨能量含量降低而降低。 實例18 在此實例中，評估能量含量對嬰兒配方之緩衝能力及緩 衝強度之影響。明確言之，測定2盎司本發明之殺菌釜滅 菌第1-2天嬰兒配方（配方3)之缓衝能力及缓衝強度且與2盎 司市售殺菌釜滅菌對照嬰兒配方（對照配方2)之緩衝能力及 緩衝強度進行比較。 測定各配方之緩衝能力及緩衝強度。明確言之，藉由以 1分鐘時間間隔向50 mL各配方中添加0.50 mL 0.500 M HC1 之等分試樣來測定配方之緩衝強度。在添加各等分試樣後 量測各配方之pH值。緩衝強度報導為使50 mL配方之pH值 自6.00降至3.00所需HC1之毫莫耳量。藉由向50 mL各配方 中添加2.75 mmol HC1來測定配方之缓衝能力。緩衝能力 報導為添加HC1後[H+]增加量及添加HC1後pH值降低量。 結果展示於以下表8中。 161200.doc -87 - 201233333 表8Formulation 13 (Day 1 / 2) Formulation 15 (Days 3-9) Control Formula 1 Kcal/L 250 420 676 Buffer Strength immol) 3.41 3.81 4.56 Buffer Capacity - pH Reduction 4.84 4.52 4.02 Buffer Capacity - 丨H+1 Increase the 6.17 mM 4.17 mM 1.20 mM 161200.doc • 86 · 201233333 As can be seen from the results described in Table 7 and Figure 3-6, the buffer strength and buffer of the formulation on Day 1-2 and the formulation of Days 3-9 The ability (as measured by pH reduction and [H+] increase) was significantly lower than the buffer strength and buffering capacity of the control formulation. Formulations 1-2 days with an energy content of 250 kcal/L had the lowest buffering capacity and buffer strength in all test formulations, indicating that buffer strength and buffering capacity decreased with decreasing energy content. Example 18 In this example, the effect of energy content on the buffering capacity and buffer strength of an infant formula was evaluated. Specifically, the buffer capacity and buffer strength of 2 ounces of the infant formula (Formulation 3) of the sterilization of the sterilization vessel of the present invention were determined and compared with the 2 ounce commercial sterilization sterilization infant formula (Control Formula 2). Buffering capacity and buffering strength were compared. The buffering capacity and buffering strength of each formulation were determined. Specifically, the buffer strength of the formulation was determined by adding 0.50 mL of an aliquot of 0.500 M HC1 to 50 mL of each formulation at 1 minute intervals. The pH of each formulation was measured after each aliquot was added. The buffer strength is reported as the millimolar amount of HC1 required to reduce the pH of the 50 mL formulation from 6.00 to 3.00. The buffering capacity of the formulation was determined by adding 2.75 mmol of HCl to 50 mL of each formulation. The buffering capacity is reported as the amount of [H+] increase after the addition of HC1 and the decrease in pH after the addition of HC1. The results are shown in Table 8 below. 161200.doc -87 - 201233333 Table 8

配方3(第1-2天） 對照配方2 Kcal/L 250 676 緩衝強度(mmol) 1.53 2.28 緩衝能力-pH降低量 4.34 4.13 緩衝能力-[H+]增加量 10.7 mM 3.72 mM 如可自表8中闡述之結果可見，第1-2天配方之緩衝強度 及緩衝能力（如由pH值降低量及增加量量測）均顯著低於對 照配方之緩衝強度及緩衝能力，顯示本發明之低熱量第1-2天殺菌釜滅菌配方之緩衝強度及緩衝能力低於習知全熱 量嬰兒配方之緩衝強度及緩衝能力。 實例19 在此實例中，評估能量含量對嬰兒配方之緩衝能力及緩 衝強度之影響。明確言之，測定32盎司本發明之無菌滅菌 第3-9天嬰兒配方（配方11)之緩衝能力及緩衝強度且與32盎 司市售無菌滅菌對照嬰兒配方（對照配方3)之緩衝能力及緩 衝強度進行比較。 測定各配方之緩衝能力及緩衝強度。明確言之，藉由以 1分鐘時間間隔向1〇〇 mL各配方中添加1.00 mL 0.500 Μ HC1之等分試樣來測定配方之緩衝強度。在添加各等分試 樣後量測各配方之pH值。緩衝強度報導為使100 mL配方 之pH值自6.00降至3.00所需HC1之毫莫耳量。藉由向100 mL各配方中添加5·50 mmol HC1來測定配方之緩衝能力。 缓衝能力報導為添加HC1後[H+]增加量及添加HC1後pH值 降低量。結果展示於以下表9中。 I6I200.doc -88- 201233333 表9Formula 3 (Day 1-2) Control Formula 2 Kcal/L 250 676 Buffer Strength (mmol) 1.53 2.28 Buffer Capacity - pH Reduction 4.34 4.13 Buffer Capacity - [H+] Increase 10.7 mM 3.72 mM As shown in Table 8 As can be seen from the results, the buffer strength and buffering capacity of the formulation on Day 1-2 (as measured by pH reduction and increase) are significantly lower than the buffer strength and buffering capacity of the control formulation, indicating the low calorie content of the present invention. The buffer strength and buffering capacity of the 1-2 day sterilization pot sterilization formula is lower than that of the conventional full calorie infant formula. Example 19 In this example, the effect of energy content on the buffering capacity and buffer strength of an infant formula was evaluated. Specifically, the buffer capacity and buffer strength of 32 ounces of the Aseptic Sterilization Day 3-9 infant formula (Formulation 11) of the present invention were determined and buffered and buffered with 32 ounces of commercially available sterile sterile control infant formula (Control Formula 3). The strength is compared. The buffering capacity and buffering strength of each formulation were determined. Specifically, the buffer strength of the formulation was determined by adding 1.00 mL of an aliquot of 0.500 Μ HC1 to 1 〇〇 mL of each formulation at 1 minute intervals. The pH of each formulation was measured after each aliquot was added. The buffer strength is reported as the millimolar amount of HC1 required to reduce the pH of the 100 mL formulation from 6.00 to 3.00. The buffering capacity of the formulation was determined by adding 5·50 mmol of HC1 to 100 mL of each formulation. The buffering capacity is reported as the increase in [H+] after the addition of HC1 and the decrease in pH after the addition of HC1. The results are shown in Table 9 below. I6I200.doc -88- 201233333 Table 9

配方11(第3-9天） 對照配方3 Kcal/L 410 676 緩衝強度(mmol) 3.46 3.84 緩衝能力-pH降低量 4.78 4.54 緩衝能力-[H+I增加量 8.51 mM 5,50 mM 如可自表9中闡述之結果可見，第3-9天配方之緩衝強度 及緩衝能力（如由pH值降低量及增加量量測）均顯著低於對 照配方之緩衝強度及緩衝能力，顯示本發明之低熱量第3-9天無菌滅菌配方之緩衝強度及缓衝能力低於習知全熱量 嬰兒配方之緩衝強度及緩衝能力》 實例20 在此實例中’評估嬰兒配方之能量含量對蛋白質水解速 率及程度之影響。明確言之，測定復原之本發明之第1 _2 天粉末嬰兒配方（配方13)及復原之本發明之第3-9天粉末嬰 兒配方（配方15)在活體外腸胃消化後之蛋白質水解程度， 且與復原之粉末對照嬰兒配方（對照配方1)之蛋白質水解程 度進行比較。Formulation 11 (Days 3-9) Control Formula 3 Kcal/L 410 676 Buffer Strength (mmol) 3.46 3.84 Buffer Capacity - pH Reduction 4.78 4.54 Buffer Capacity - [H+I Increase 8.51 mM 5,50 mM As can be seen from the results set forth in Table 9, the buffer strength and buffering capacity of the formulations on days 3-9 (as measured by pH reduction and increase) were significantly lower than the buffer strength and buffering capacity of the control formulation, indicating that the present invention The buffer strength and buffering capacity of the low calorie 3-9 day sterile sterilization formula is lower than the buffer strength and buffering capacity of the conventional full calorie infant formula. Example 20 In this example, 'evaluate the energy content of the infant formula to the rate and extent of proteolysis influences. Specifically, the degree of protein hydrolysis of the reconstituted first 1-2 day powder infant formula (Formulation 13) of the present invention and the reconstituted 3-9 day powder infant formula of the present invention (Formulation 15) after intestine digestion in vitro, And compared to the degree of protein hydrolysis of the reconstituted powder control infant formula (Control Formula 1).

使用12.2 g配方加240 mL水復原配方13，使用21.4 g配 方加240 mL水復原配方15且使用35.0 g配方加240 mL水復 原對照配方1。藉由使復原配方經活體外腸胃消化來製備 消化物。明確言之’使用6 M HC1調節40 mL各復原配方之 pH值至4.5。1.00 mL USP胃蛋白酶（於水中以56 mg/mI^ 備）添加至配方中且在室溫下攪拌所得混合物1小時。使用 10 N NaOH調節混合物之pH值至7.2。接著添加4 〇〇 mL 161200.doc -89 · 201233333 USP胰酶澱粉酶/蛋白酶（於水中以6.94 mg/mL製備）加USP 胰酶脂肪酶（於水中以6.94 mg/mL製備）且在室溫下攪拌混 合物2小時。所得消化物在20°C下以31，000xg離心4小時。 使用Superdex®肽10/300 GL凝膠過遽管柱（Amersham Biosciences)藉由HPLC分析上清液。明確言之，5 mg上清 液添加至1 mL移動相溶液（700 mL Milli-Q®水、300 mL乙 腈、1.00 mL TFA)中且所得溶液在環境溫度下運行於 Superdex®管柱上（流動速率：0.4毫升/分鐘；彳貞測：205 nm下UV ;注射：10 μι ;運行時間：80分鐘）以測定消化 物中蛋白質之分子量中值及消化物中分子量大於5000道爾 頓之蛋白質量（佔總蛋白質百分比）。該等測定值為蛋白質 消化程度之指標。亦使用習知方法使用酸水解/胺基酸概 況測試消化物離心後產生之集結塊中不可溶蛋白質之存 在。結果展示於.以下表10以及圖7-9中。 表10 配方13 (第1-2天） 配方15 (第3-9天） 對照配方1 Kcal/L 250 420 676 蛋白質MW中值(Da) 777 925 1022 蛋白質&gt;5000 Da(佔總蛋白質百分比） 8.4% 13.4% 14.0% 不可溶蛋白質a(mg/L) 24 59 156 消化物高速離心後集結塊中之總蛋白質 如可自該等結果可見，與對照配方相比，第1 -2天配方 及第3-9天配方中之蛋白質水解更廣泛。此外，所有三種 消化指標（蛋白質MW中值、大於5000 Da之蛋白質量及不 161200.doc -90· 201233333 可溶蛋白質量）均隨能量含量降低而降低。該等結果顯示 蛋白質消化率與能量含量反相關。 實例21 在此實例中，評估嬰兒配方之能量含量對蛋白質水解速 率及程度之影響。明確言之，測定2盎司本發明之殺菌爸 滅菌第1-2天嬰兒配方（配方3)在活體外腸胃消化後之蛋白 質水解程度且與2盎司市售殺菌釜滅菌對照嬰兒配方（對照 配方2)之蛋白質水解程度進行比較。 使用實例20中闡述之程序藉由使配方經活體外腸胃消化 來製備消化物。消化物在20°C下以31,000xg離心4小時。 使用以上實例20中闡述之程序使用Superdex®肽10/300 GL 凝膠過濾、管柱（Amersham Biosciences)藉由HPLC分析上清 液，且測定消化物中蛋白質之分子量中值及消化物中分子 量大於5000道爾頓之蛋白質量（佔總蛋白質百分比）。亦使 用實例20中描述之酸水解/胺基酸型態分析測試消化物離 心後產生之集結塊中不可溶蛋白質之存在。結果展示於以 下表11中。 亦使用酸水解及HPLC測試消化物中梅納反應標記物糠 胺酸之存在。該等結果亦展示於以下表11中。 表11 配方3(第1-2天） 對照配方2 Kcal/L 250 676 蛋白質MW中值(Da) 789 992 蛋白質&gt;5000 Da(佔總蛋白質百分比） 3.77% 8.81% 不可溶蛋白質a (mg/L) 48 471 糠胺酸(佔總離胺酸莫耳百分比） 0.84% 2.61% 消化物高速離心後集結塊中之總蛋白質 161200.doc •91 - 201233333 如可自該等結果可見，與對照配方相比，第1-2天配方 中之蛋白質水解更廣泛。所有三種消化指標（蛋白質MW中 值、大於5000 Da之蛋白質量及不可溶蛋白質量）均隨能量 含量降低而降低。該等結果顯示蛋白質消化率與能量含量 反相關。此外，第1 -2天配方之梅納反應標記物糠胺酸含 量低於對照配方。該等結果顯示與習知全熱量嬰兒配方相 比，本發明之低熱量第1 -2天殺菌釜滅菌配方對梅納反應 之敏感度較低。 實例22 在此實例中，評估嬰兒配方之能量含量對蛋白質水解速 率及程度之影響。明確言之，測定32盘司本發明之無菌滅 菌第3-9天嬰兒配方（配方11)在活體外腸胃消化後之蛋白質 水解程度且與32盎司市售無菌滅菌對照嬰兒配方（對照配 方3 )之蛋白質水解程度進行比較。 使用實例20中闡述之程序藉由使配方經活體外腸胃消化 來製備消化物。消化物在2〇eC下以3 1，000xg離心4小時。 使用以上實例20中闡述之程序使用Superdex⑧肽1〇/3〇〇 gl 凝膠過濾管柱（Amersham Biosciences)藉由HPLC分析上清 液，且測定消化物中蛋白質之分子量（MW)中值及消化物 中分子量大於5000道爾頓之蛋白質量（佔總蛋白質百分 比）。亦使用實例20中描述之酸水解/胺基酸型態分析測試 消化物離心後產生之集結塊中不可溶蛋白質之存在。結果 展示於以下表12中。 161200.doc •92· 201233333 表12 配方11(第3-9天） 對照配方3 Kcal/L 410 676 蛋白質MW中值(Da) 799 978 蛋白質&gt;5000 Da(佔總蛋白質百分比） 2.5% 9.5% 不可溶蛋白質a(mg/L) 110 400 消化物高速離心後集結塊中之總蛋白質 如可自該等結果可見，與對照配方相比，第3-9天配方 中之蛋白質水解更廣泛。所有三種消化指標（蛋白質MW中 值、大於5000 Da之蛋白質量及不可溶蛋白質量）均隨能量 含量降低而降低。該等結果顯示蛋白質消化率與能量含量 反相關。 實例23 在此實例中，評估嬰兒配方之能量含量對蛋白質水解速 率及程度之影響。明確言之，測定復原之本發明之第1-2 天粉末嬰兒配方（配方13)及復原之本發明之第3-9天粉末嬰 兒配方（配方15)在胰酶消化後之蛋白質水解程度，且與復 原之市售粉末對照嬰兒配方（對照配方1)在胰酶消化後之蛋 白質水解程度進行比較。 使用12.2 g配方加240 mL水復原配方13，使用21.4 g配 方加240 mL水復原配方15且使用35.0 g配方加240 mL水復 原對照配方1。藉由使復原配方經胰酶消化來製備消化 物。明確言之，在20 mL小瓶中，9.00 mL 0.05 Μ NaH2P〇4(pH 7.5)添加至9.00 mL各配方中。2.00 mL豬胰酶 (於pH 7.5緩衝劑中以4.0 g/L製備）添加至配方中且小瓶置 161200.doc -93 - 201233333 放於37°C水浴中71分鐘。71分鐘後，1.5 mL混合物等分試 樣轉移入HPLC自動取樣器小瓶中且捲曲密封小瓶。密封 小瓶置放於l〇〇°C加熱模組中5分鐘以終止胰酶消化。用 1.00 mL 8.30/6.00/0.02 (v/v)水/乙腈/三氟乙酸稀釋0.400 mL所得消化物。稀釋之消化物在室溫下以14,000xg離心5 分鐘。使用以上實例20中闡述之程序使用Superdex®肽 1 0/3 00 GL凝膠過遽管柱（Amer sham Bio sciences)藉由 HPLC 分析上清液，且測定消化物中蛋白質之分子量（MW)中值 及消化物中分子量大於5000道爾頓之蛋白質量（佔總蛋白 質百分比）。結果展示於以下表13以及圖10及11中。 表13 配方13 (第1-2天） 配方15 (第3-9天） 對照配方1 Kcal/L 250 420 676 蛋白質MW中值(Da) 680 748 853 蛋白質&gt;5000 Da(佔總蛋白質百分比） 2.15% 2.54% 3.03% 如可自該等結果可見，與對照配方相比，第1-2天配方 及第3-9天配方中之蛋白質水解更廣泛。此外，兩種消化 指標（蛋白質MW中值、大於5000 Da之蛋白質量）均隨能量 含量降低而降低。該等結果顯示蛋白質消化率與能量含量 反相關。 實例24 在此實例中，評估嬰兒配方之能量含量對蛋白質水解速 率及程度之影響。明確言之，測定2盎司本發明之殺菌爸 滅菌第1-2天嬰兒配方（配方3)在胰酶消化之前及之後的蛋 161200.doc -94- 201233333 白質水解程度且與2盘司市售殺菌爸滅菌對照嬰兒配方（對 照配方2)在胰酶消化之前及之後的蛋白質水解程度進行比 較。 除嬰兒配方/胰酶混合物保持在37°C水浴中僅60分鐘 外，使用與實例23中所闡述相同之程序藉由使配方經胰酶 消化來製備消化物。稀釋之消化物在室溫下以14,OOOxg離 心5分鐘。使用Superdex®肽10/300 GL凝膠過濾管柱 (Amersham Biosciences)使用以上實例20中所闡述之程序 藉由HPLC分析消化之前的上清液以及嬰兒配方之樣品， 且測定消化之前嬰兒配方中蛋白質之分子量中值及60分鐘 胰酶消化後蛋白質之中值分子量。結果展示於以下表14 中〇 表14 配方3(第1-2天） 對照配方2 Kcal/L 250 676 消化前蛋白質MW中值(Da) 14,774 19,120 60分鐘消化後蛋白質MW中值(Da) 801 1128 如可自該等結果可見，與對照配方相比，低熱量第1-2 天配方中之蛋白質水解速率較快。此外，60分鐘胰酶消化 後之MW中值與嬰兒配方之熱量密度成正比，顯示蛋白質 消化率與能量含量反相關。 實例25 在此實例中，評估嬰兒配方之能量含量對蛋白質水解速 率及程度之影響。明確言之，測定復原之本發明之第1-2 161200.doc -95- 201233333 天粉末嬰兒配方（配方12)或第3-9天粉末嬰兒配方（配方 14)、2盎司本發明之第1-2天殺菌釜滅菌嬰兒配方（配方1及 2)或第3-9天殺菌爸滅菌嬰兒配方（配方5)及32盘司本發明 之第3-9天無菌滅菌嬰兒配方（配方9)在胰酶消化（粉末）或 活體外GI消化（液體）後之蛋白質水解程度且與復原之市售 粉末對照嬰兒配方（對照配方1)、2盎司市售殺菌釜滅菌對 照嬰兒配方（對照配方2)及32盎司市售無菌滅菌對照配方 (對照配方3)之蛋白質水解程度進行比較。 使用12.2 g配方加240 mL水復原配方12，使用21.4 g配 方加240 mL水復原配方14且使用35.0 g配方加240 mL水復 原對照配方1。使用與上文所闡述相同之程序藉由使配方 (或復原配方）經胰酶消化來製備消化物。使用以上實例20 中闡述之程序使用Superdex®肽10/300 GL凝膠過滤管柱 (Amersham Biosciences)藉由HPLC分析上清液，且測定消 化物中蛋白質之分子量（MW)中值及消化物中分子量大於 5000道爾頓之蛋白質量（佔總蛋白質百分比）。結果展示於 以下表1 5中。 表15 配方 能量 (kcal/L) 形式 蛋白質MW&gt; 5000 Da(佔總蛋白質百分比） 蛋白質MW中 值(Da) 對照配方1 676 粉末 17.9% 1050 g己方14(第3-9天)a 406 粉末 10.9% 846 g己方14(第3-9天） 406 粉末 8.4% 812 配方12(第1-2天） 270 粉末 5.2% 717 對照配方2 676 殺菌釜滅菌 13.7% 988 161200.doc •96- 201233333 配方 能量 (kcal/L) 形式 蛋白質MW&gt; 5000 Da(佔總蛋白質百分比） 蛋白質MW中 值(Da) 配方5(第3-9天） 406 殺菌釜滅菌 5.3% 789 配方1(第1-2天） 270 殺菌釜滅菌 3.9% 730 配方2(第1-2天） 270 殺菌爸滅菌 2.9% 707 對照配方3 676 無菌滅菌 10.2% 963 配方9(第3-9天） 406 無菌滅菌 4.1% 801 配方14測試2次。 如可自該等結果可見，與對照配方相比，第1-2天配方 及第3-9天配方中之蛋白質水解更廣泛。此外，兩種消化 指標（蛋白質中值MW、大於5000 Da之蛋白質量）均隨能量 含量降低而降低。該等結果顯示蛋白質消化率與能量含量 反相關。 實例26 此實例中，評估微量營養素含量對第1-2天殺菌爸滅菌 嬰兒配方及第3-9天無菌滅菌嬰兒配方之乳液穩定性之影 響。明確言之，比較32盎司具有高（配方11)或低（配方9)微 量營養素含量之第3-9天無菌滅菌嬰兒配方之乳液穩定性 及2盎司具有高（配方3)或低（配方1)微量營養素含量之第1-2天殺菌釜滅菌嬰兒配方之乳液穩定性。 使用蛋白質負載量（表示為配方高速離心後形成之乳油 層之蛋白質百分比）測定乳液穩定性。各配方之蛋白質負 載量係藉由將36-3 8公克配方傾入配衡之50 mL離心管中且 封蓋離心管來測定。接著將封蓋之離心管置放於JA-20定 角旋轉器（Beckman Coulter，P/N 334831)中且旋轉器置放 161200.doc -97- 201233333 於 Beckman J2-HS 離心機（Beckman Coulter)中。樣 σ 在 20°C下以31，〇〇〇Xg離心8小時》離心後，樣品上形成乳油 層。乳油層轉移入配衡燒杯中且記錄其重量。上清液傾入 獨立燒杯中且再次稱重離心管以測定集結塊重量。 使用酸水解/胺基酸測定技術測定乳油層中之蛋白質 量。結果闡述於以下表16中。 表16 配方 配方11(第3-9天） 配方9(第3-9天）Formulation 13 was reconstituted using 12.2 g of formula plus 240 mL of water, Formulation 15 was reconstituted using 21.4 g of Formulation plus 240 mL of water and Formulation 1 was reconstituted using 35.0 g of Formula plus 240 mL of water. The digest is prepared by in vitro digestion of the reconstituted formula. Specifically, '6 M HC1 was used to adjust the pH of each 40 mL of the reconstituted formula to 4.5. 1.00 mL of USP pepsin (prepared in water at 56 mg/mI) was added to the formulation and the resulting mixture was stirred at room temperature for 1 hour. . The pH of the mixture was adjusted to 7.2 using 10 N NaOH. Then add 4 〇〇mL 161200.doc -89 · 201233333 USP trypsin amylase / protease (prepared in water at 6.94 mg / mL) plus USP trypsin lipase (prepared in water at 6.94 mg / mL) and at room temperature The mixture was stirred for 2 hours. The resulting digest was centrifuged at 31,000 xg for 4 hours at 20 °C. Supernatants were analyzed by HPLC using a Superdex® Peptide 10/300 GL gel column (Amersham Biosciences). Specifically, 5 mg of supernatant was added to 1 mL of mobile phase solution (700 mL Milli-Q® water, 300 mL acetonitrile, 1.00 mL TFA) and the resulting solution was run on Superdex® column at ambient temperature (flow Rate: 0.4 ml/min; speculation: UV at 205 nm; injection: 10 μιη; run time: 80 minutes) to determine the median molecular weight of the protein in the digest and the amount of protein with a molecular weight greater than 5000 Daltons in the digest (% of total protein). These measurements are an indicator of the degree of protein digestion. The presence of insoluble proteins in the agglomerates produced by centrifugation of the digests was also tested using acid hydrolysis/amino acid profiles using conventional methods. The results are shown in Table 10 below and in Figures 7-9. Table 10 Formulation 13 (Day 1-2) Formulation 15 (Days 3-9) Control Formula 1 Kcal/L 250 420 676 Protein MW Median (Da) 777 925 1022 Protein &gt; 5000 Da (% of total protein) 8.4% 13.4% 14.0% Insoluble protein a (mg/L) 24 59 156 The total protein in the agglomerate after centrifugation at high speed can be seen from these results, compared to the control formula, the first 1-2 day formula and Protein hydrolysis in Formulations 3-9 is more extensive. In addition, all three digestive parameters (median protein MW, protein content greater than 5000 Da, and soluble protein content not 161200.doc -90· 201233333) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content. Example 21 In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis was assessed. Specifically, the degree of protein hydrolysis of the 2 ounce infant formula of Formulation 1-2 of the present invention (Formulation 3) after intestine digestion in vitro and the control of 2 ounces of commercial sterilization sterilization infant formula (Control Formula 2) was determined. The degree of protein hydrolysis is compared. The digest was prepared using the procedure set forth in Example 20 by digesting the formulation in vitro and in vivo. The digest was centrifuged at 31,000 xg for 4 hours at 20 °C. The supernatant was analyzed by HPLC using Superdex® Peptide 10/300 GL gel filtration, column (Amersham Biosciences) using the procedure set forth in Example 20 above, and the molecular weight of the protein in the digest and the molecular weight in the digest were determined to be greater than A protein content of 5000 daltons (% of total protein). The acid hydrolysis/amino acid type analysis described in Example 20 was also used to test for the presence of insoluble proteins in the agglomerates produced after centrifugation of the digest. The results are shown in Table 11 below. The presence of the Mena reaction label guanamine in the digest was also tested using acid hydrolysis and HPLC. These results are also shown in Table 11 below. Table 11 Formulation 3 (Day 1-2) Control Formula 2 Kcal/L 250 676 Protein MW Median (Da) 789 992 Protein &gt; 5000 Da (% of total protein) 3.77% 8.81% Insoluble Protein a (mg/ L) 48 471 Proline (% of total oleic acid molars) 0.84% 2.61% Total protein in the agglomerates after high-speed centrifugation of the digestible 161200.doc •91 - 201233333 As can be seen from these results, the control formula In contrast, the protein hydrolysis in the formulation on Day 1-2 is more extensive. All three digestion indicators (median MW protein, protein content greater than 5000 Da, and insoluble protein) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content. In addition, the Maya reaction label methionine content of the first 1-2 day formulation was lower than the control formulation. These results show that the low calorie 1-2 day autoclave sterilization formulation of the present invention is less sensitive to the Mena reaction than the conventional full calorie infant formula. Example 22 In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis was assessed. Specifically, the degree of protein hydrolysis of the aseptically invasive baby formula 3 (Formulation 11) of the present invention after intestine digestion in vitro was determined and compared with 32 ounces of commercially available sterile sterile control infant formula (Control Formula 3) The degree of protein hydrolysis is compared. The digest was prepared using the procedure set forth in Example 20 by digesting the formulation in vitro and in vivo. The digest was centrifuged at 3 1,000 xg for 4 hours at 2 〇eC. The supernatant was analyzed by HPLC using a Superdex8 peptide 1〇/3〇〇gl gel filtration column (Amersham Biosciences) using the procedure set forth in Example 20 above, and the molecular weight (MW) of the protein in the digest was determined and digested. The amount of protein in the molecular weight greater than 5000 Daltons (% of total protein). The acid hydrolysis/amino acid type analysis described in Example 20 was also used to test for the presence of insoluble proteins in the agglomerates produced after centrifugation of the digest. The results are shown in Table 12 below. 161200.doc •92· 201233333 Table 12 Formulation 11 (Days 3-9) Control Formula 3 Kcal/L 410 676 Protein MW Median (Da) 799 978 Protein &gt; 5000 Da (% of total protein) 2.5% 9.5% Insoluble Protein a (mg/L) 110 400 The total protein in the agglomerates after centrifugation at high speed can be seen from these results, and the protein hydrolysis in Formulations 3-9 is more extensive than in the control formulation. All three digestion indicators (median MW protein, protein content greater than 5000 Da, and insoluble protein) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content. Example 23 In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis was assessed. Specifically, the degree of protein hydrolysis after trypsinization of the reconstituted powdered infant formula of Formula 1-2 of the present invention (Formulation 13) and the reconstituted Powdered Infant Formula 3 (Formulation 15) of the present invention, The degree of protein hydrolysis after trypsinization was compared to the recovered commercial powdered infant formula (Control Formula 1). Formulation 13 was reconstituted using 12.2 g of formula plus 240 mL of water, Formulation 15 was reconstituted using 21.4 g of Formulation plus 240 mL of water and Formulation 1 was reconstituted using 35.0 g of Formula plus 240 mL of water. Digests were prepared by trypsinizing the reconstituted formula. Specifically, 9.00 mL of 0.05 Μ NaH2P〇4 (pH 7.5) was added to 9.00 mL of each formulation in a 20 mL vial. 2.00 mL of porcine pancreatin (prepared at 4.0 g/L in pH 7.5 buffer) was added to the formulation and vial 161200.doc -93 - 201233333 was placed in a 37 ° C water bath for 71 minutes. After 71 minutes, 1.5 mL of the aliquot of the mixture was transferred to a HPLC autosampler vial and the vial was crimped. The sealed vial was placed in a l ° ° C heating module for 5 minutes to stop trypsin digestion. The resulting digest was diluted 0.400 mL with 1.00 mL of 8.30/6.00/0.02 (v/v) water/acetonitrile/trifluoroacetic acid. The diluted digest was centrifuged at 14,000 xg for 5 minutes at room temperature. The supernatant was analyzed by HPLC using a Superdex® peptide 1 0/3 00 GL gel column (Amer sham Bio sciences) using the procedure set forth in Example 20 above, and the molecular weight (MW) of the protein in the digest was determined. The value and the amount of protein in the digestate with a molecular weight greater than 5000 Daltons (% of total protein). The results are shown in Table 13 below and Figures 10 and 11. Table 13 Formulation 13 (Day 1-2) Formulation 15 (Days 3-9) Control Formula 1 Kcal/L 250 420 676 Protein MW Median (Da) 680 748 853 Protein &gt; 5000 Da (% of total protein) 2.15% 2.54% 3.03% As can be seen from these results, the protein hydrolysis in Formulations 1-2 and Days 3-9 was more extensive than in the control formulations. In addition, both digestion indices (median protein MW, protein content greater than 5000 Da) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content. Example 24 In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis was assessed. Specifically, 2 ounces of the 1-2 days old baby formula of the sterilized dad sterilization of the present invention (Formulation 3) was prepared before and after trypsinization. Eggs 161200.doc -94 - 201233333 White matter hydrolysis degree and marketed with 2 plates The degree of protein hydrolysis of the sterilized dad-sterilized control infant formula (Control Formula 2) before and after trypsinization was compared. Digests were prepared by trypsinizing the formulation using the same procedure as described in Example 23, except that the infant formula/pancreatin mixture was maintained in a 37 °C water bath for only 60 minutes. The diluted digest was centrifuged at 4,000 xg for 5 minutes at room temperature. The supernatant before digestion and the sample of the infant formula were analyzed by HPLC using a Superdex® Peptide 10/300 GL Gel Filtration Column (Amersham Biosciences) using the procedure set forth in Example 20 above, and the protein in the infant formula prior to digestion was determined. The median molecular weight and the median molecular weight of the protein after trypsin digestion for 60 minutes. The results are shown in Table 14 below. Table 14 Formulation 3 (Day 1-2) Control Formula 2 Kcal/L 250 676 Pre-digested Protein MW Median Value (Da) 14,774 19,120 60 min Digested Protein MW Median Value (Da) 801 1128 As can be seen from these results, the rate of protein hydrolysis in the low calorie 1-2 day formulation was faster compared to the control formulation. In addition, the median MW after pancreatic digestion for 60 minutes is directly proportional to the caloric density of the infant formula, indicating that protein digestibility is inversely related to energy content. Example 25 In this example, the effect of the energy content of the infant formula on the rate and extent of proteolysis was assessed. Specifically, the 1-2 161200.doc -95 - 201233333 day powder infant formula (Formulation 12) or the 3-9 day powder infant formula (Formulation 14) of the present invention, 2 ounces of the first invention of the present invention - 2 days Sterilization Sterilization Infant Formula (Formulations 1 and 2) or Day 3-9 Sterilization Daddy Infant Formula (Formulation 5) and 32 Discs of the 3rd Day Sterile Sterilized Infant Formula (Formulation 9) of the Invention Degree of protein hydrolysis after trypsinization (powder) or in vitro GI digestion (liquid) and compared to the reconstituted commercial powder control infant formula (Control Formula 1), 2 ounces of commercial sterilized sterilized control infant formula (Control Formula 2) The degree of protein hydrolysis of the 32 ounce commercial sterile sterile control formulation (Control Formula 3) was compared. Formulation 12 was reconstituted using 12.2 g of formula plus 240 mL of water, Formulation 14 was reconstituted using 21.4 g of Formulation plus 240 mL of water and Reconstruction Control Formulation 1 was reconstituted using 35.0 g of formula plus 240 mL of water. The digest is prepared by trypsinizing the formulation (or reconstituted formulation) using the same procedure as described above. The supernatant was analyzed by HPLC using a Superdex® Peptide 10/300 GL Gel Filtration Column (Amersham Biosciences) using the procedure set forth in Example 20 above, and the molecular weight (MW) of the protein in the digest and the digest were determined. The amount of protein with a molecular weight greater than 5000 Daltons (% of total protein). The results are shown in Table 15 below. Table 15 Formulation Energy (kcal/L) Form Protein MW> 5000 Da (% of total protein) Protein MW Median (Da) Control Formulation 1 676 Powder 17.9% 1050 g of Radix 14 (Day 3-9) a 406 Powder 10.9 % 846 g own 14 (days 3-9) 406 powder 8.4% 812 Formulation 12 (Day 1-2) 270 Powder 5.2% 717 Control Formula 2 676 Sterilization Sterilization 13.7% 988 161200.doc •96- 201233333 Formula Energy (kcal/L) Form Protein MW> 5000 Da (% of total protein) Protein MW Median (Da) Formula 5 (Days 3-9) 406 Sterilization Sterilization 5.3% 789 Formula 1 (Day 1-2) 270 Sterilization Sterilization 3.9% 730 Formulation 2 (Day 1-2) 270 Sterilization Dad Sterilization 2.9% 707 Control Formula 3 676 Sterile Sterilization 10.2% 963 Formulation 9 (Days 3-9) 406 Sterile Sterilization 4.1% 801 Formulation 14 Test 2 Times. As can be seen from these results, the protein hydrolysis in Formulations 1-2 and Days 3-9 was more extensive than in the control formulations. In addition, both digestion indices (protein median MW, protein content greater than 5000 Da) decreased with decreasing energy content. These results show that protein digestibility is inversely related to energy content. Example 26 In this example, the effect of micronutrient content on emulsion stability of the 1-2 days of sterilized dad sterilized infant formula and the 3-9 day sterile sterilized infant formula was evaluated. Specifically, compare 32 ounces of high stability (Formulation 11) or low (Formulation 9) micronutrient content to the 3-9 day sterile sterilized infant formula for emulsion stability and 2 ounces with high (Formulation 3) or low (Formulation 1) The emulsion stability of the sterilized infant formula for the first 1-2 days of micronutrient content. The emulsion stability was determined using the protein loading (expressed as the percentage of protein in the emulsifiable layer formed after high speed centrifugation of the formulation). The protein loading of each formulation was determined by pouring 36-3 8 grams of the formulation into a tared 50 mL centrifuge tube and capping the centrifuge tube. The capped centrifuge tube was then placed in a JA-20 fixed angle rotator (Beckman Coulter, P/N 334831) and the rotator was placed 161200.doc -97-201233333 in a Beckman J2-HS centrifuge (Beckman Coulter) in. The sample σ was centrifuged at 31 ° C for 8 hours at 20 ° C. After centrifugation, a cream layer was formed on the sample. The cream layer was transferred to a tared beaker and its weight recorded. The supernatant was poured into a separate beaker and the centrifuge tube was weighed again to determine the aggregate weight. The amount of protein in the cream layer was determined using an acid hydrolysis/amino acid assay technique. The results are set forth in Table 16 below. Table 16 Formulation Formulation 11 (Days 3-9) Formulation 9 (Days 3-9)

406 微量營養素含 J 高 形式 無菌滅菌 無菌滅菌 乳油層中蛋白質百分比 量百分比近似值） 5.1% 4.7% 配方3(第1-2天） 250 殺菌釜滅菌 配方1(第1-2天） 270 低 殺菌釜滅菌 4.6% 5.9%406 Micronutrients containing J high-level sterile sterile sterile emulsifiable concentrate layer percentage of protein percentage) 5.1% 4.7% Formulation 3 (Day 1-2) 250 Sterilization Sterilization Formula 1 (Day 1-2) 270 Low Sterilizer Sterilization 4.6% 5.9%

蛋白質負載值為乳液穩定性指標。明確言之乳液穩定 性通常隨蛋白質負載值增加而增加。如可自以上結果可 見’具有低微量營養素含量之第^天殺菌蚤滅菌配方（亦 即配方1)中之蛋白質負載值高於具有高微量營養素含量之 第1 -2天&amp;菌爸滅菌方（亦即配方3)中之蛋白質負載值。 該等結果顯示’與可比較之具有高微量營養素含量之配方 相比’具有低微#營養素含量之第卜2天殺菌爸滅菌配方 中之乳液穩定性增加。未發現高微量營養素含量無菌滅菌 配方與低微量營養音+ ^ 贷量無菌滅菌配方之間存在蛋白質負 載之顯著差異。 161200.doc -98· 201233333 實例27 此實例中’評估微量營養素含量訝第3 _9天殺菌釜滅菌 配方之乳液穩疋性之影響。明破s之，比較2盎司具有高 (配方8)或低（配方6)微量營養素含量之第3_9天殺菌釜滅菌 嬰兒配方之乳液穩定性。 使用蛋白質負載量（表示為配方高速離心後形成之乳油 層之蛋白質百分比）測定乳液穩定性。使用實例26中闡述 之程序測定各配方之蛋白質負載量。亦計算乳油層量（以 全部產品重量計）及乳油層中之蛋白質量（以全部產品重量 計）。結果闡述於以下表17中。 表17 配方 能量 微量營養 乳油層中蛋白質百 全部產品之乳油層蛋 (kcal/U 素含量 分比(w/w) 白質百分比(w/w) 配方6(第3-9天） 406 低 6.9% 0.35% 配方8(第3·9天） 410 高 5.1% 0.22% 如可自該等結果可見，具有低微量營養素含量之配方6 中之蛋白質負載值高於高微量營養素配方（亦即配方8)中之 蛋白質負載值。與配方8相比，配方6亦形成較大的乳油層 且乳油層中之蛋白質百分比（以全部產品重量計）較高。該 等結果顯示，與可比較之具有高微量營養素含量之配方相 比’具有低微量營養素含量之第3_9天殺菌釜滅菌配方中 之乳液穩定性增加。與低微量營養素含量第1_2天殺菌釜 滅菌配方（參見配方丨’實例26)相比，低微量營養素含量第 3-9天殺菌釜滅菌配方（亦即配方6)亦具有較高蛋白質負載 161200.doc -99- 201233333 值且因此乳液穩定性增加。 實例28 此實例中，評估微量營養素含量對第1-2天及第3-9天殺 菌爸滅菌配方及第3-9天無菌滅菌配方之顏色之影響。 使用艾格壯顏色法評估配方之顏色品質。艾格壯顏色法 使用分光光度計以〇(黑色）至1〇〇(白色）等級量測自樣品反 射之光之百分比。亮色嬰兒配方（其通常受消費者偏愛）具 有較高艾格壯顏色計分，而深色配方具有較低計分。在多 個時間週期量測之本發明之低及高微量營養素含量殺菌爸 滅菌及無菌滅菌配方之艾格壯顏色計分闡述於以下表 18(殺菌釜滅菌配方）及表19(第3-9天無菌滅菌配方）中。 表18 :殺菌釜滅菌配方 配方 能量 (kcal/L) 微量營養素含量 時間間隔 艾格壯顏色計分(％)a 配方3 (第1-2天） 250 尚 0天 39.3 1個月 … 2個月 33.3 4個月 30.2 9個月 28.5 12個月 28.2 配方4 (第1-2天） 250 0天 44.1 1個月 … 3個月 37.5 6個月 35.4 9個月 33.4 12個月 33.0 配方1 (第1-2天） 270 低 0天 47.9 2個月 43.7 4個月 42.2 6個月 40.3 9個月 38.6 配方2 (第1-2天） 270 低 0天 54.4 3個月 49.7 161200.doc •100· 201233333 配方 能量 (kcal/L) 微量營養素含量 時間間隔 艾格壯顏色計分(％)a 6個月 47.8 配方8 (第3-9天） 410 尚 0天 39.4 配方5 (第3-9天） 406 低 0天 51.1 3個月 48.8 6個月 46.0 配方6 (第3·9天） 406 低 0天 45.3 配方7 (第3-9天） 406 低 0天 46.2 (---)意謂未測試 a對於所有量測，均使用Agtron M-45分光光度計（藍色濾光 片-43 6 nm)測定艾格壯顏色計分。 表19:第3-9天無菌滅菌配方 配方 能量 (kcal/L) 微量營養素含量 時間間隔 艾格壯顏色計分(％)a 配方11 410 尚 0天 53.1 1個月 49.7 2個月 ... 4個月 ... 12個月 46.2 配方10 410 南 0天 56.5 1個月 ___ 3個月 51.7 6個月 53.1 9個月 51.4 12個月 47.6 配方9 406 低 0天 61.5 1個月 ___ 2個月 60.0 6個月 56.9 9個月 53.8 I61200.doc -101- 201233333 (---)意謂未測試 a對於所有量測，均使用Agtron M-45分光光度計（藍色濾光 片-43 6 nm)測定艾格壯顏色計分。 如可自該等結果可見’與具有高微量營養素含量之殺菌 爸滅菌第1-2天嬰兒配方相比，具有低微量營養素含量之 殺菌爸滅菌第1-2天嬰兒配方具有較高艾格壯顏色計分且 因此具有較亮的顏色外觀。在第3·9天殺菌釜滅菌配方及 第3-9天無菌滅菌配方下獲得類似結果，其中低微量營養 素含量配方之艾格壯顏色計分高於可比較之具有高微量營 養素含量之配方。甚至在長時間後（在一些情況下，在產 品調配後多達9個月）亦觀測到低微量營養素配方相比於可 比較之高微量營養素配方之顏色改良。該等結果顯示本發 明之具有低微量營養素含量之嬰兒配方與具有高微量營養 素含量之可比較之配方相比具有較亮且較淡的顏色外觀。 實例29 此實例中，評估微量營養素含量對殺菌蚤滅菌第卜之天 配方之粒徑分佈及乳油分離速度之影響。 明確言之’使用Beckman Coulter LS 13 320光散射機器 測定2盘司具有高微量營養素含量（配方3)或低微量營養素 含量（配方1)之殺菌釜滅菌第丨_2天配方之粒徑分佈。結果 展示於圖12中。 如可自圖12中可見，低微量營養素第1_2天殺菌釜滅菌 配方（配方1)中之大部分顆粒之尺寸介於約〇·1 μπι與約〇 8 μιη之間’少部分顆粒介於約1 μιη與約8 μπι之間。相比之 161200.doc •102· 201233333 下’高微量營養素第1_2天殺菌釜滅菌配方（配方3)之粒徑 分佈更平均地在約〇.i μπ1至約7 μπι範圍内。 由粒徑分佈測定各配方之平均粒徑且用於計算各配方之 乳油分離速度。明確言之，使用以下方程式計算乳油分離 速度：The protein loading value is an indicator of emulsion stability. It is clear that emulsion stability generally increases as the protein loading value increases. For example, it can be seen from the above results that the protein load value of the second day sterilization sterilizing formula (ie, formula 1) with low micronutrient content is higher than that of the first 1-2 days with high micronutrient content. The protein loading value in Formulation 3. These results show an increase in emulsion stability in the second day of sterilization with a low micronutrient content compared to a comparable formula with a high micronutrient content. There was no significant difference in protein load between the aseptic sterilization formula for high micronutrient content and the low micronutrient tone + ^ bulk aseptic formulation. 161200.doc -98· 201233333 Example 27 In this example, the effect of evaluating the micronutrient content on the stability of the emulsion of the formulation for the 3rd_9th day of sterilization. Clearly sip the emulsion stability of the 2 ounce antibacterial autoclave infant formula with 2 ounces of high (Formulation 8) or low (Formulation 6) micronutrient content. The emulsion stability was determined using the protein loading (expressed as the percentage of protein in the emulsifiable layer formed after high speed centrifugation of the formulation). The protein loading of each formulation was determined using the procedure set forth in Example 26. The amount of cream layer (by weight of the total product) and the amount of protein in the cream layer (based on the total weight of the product) were also calculated. The results are set forth in Table 17 below. Table 17 Formulated energy micro-nutrient cream layer of protein in all layers of the product of the cream layer egg (kcal / U content ratio (w / w) white matter percentage (w / w) Formula 6 (days 3-9) 406 low 6.9% 0.35% Formulation 8 (Day 3.9) 410 High 5.1% 0.22% As can be seen from these results, the protein loading value in Formula 6 with low micronutrient content is higher than the high micronutrient formulation (ie Formula 8) The protein loading value in the formula. Compared with the formula 8, the formula 6 also forms a larger cream layer and the percentage of protein in the cream layer (by weight of the total product) is higher. The results show that the sample has a high trace amount. The formulation of the nutrient content was increased compared to the emulsion stability of the 3rd-9th sterilizer formulation with low micronutrient content. Compared with the low micronutrient content 1st day sterilization sterilizer formulation (see formula 丨 'Example 26), Low micronutrient content Day 3-9 Sterilization Sterilization Formulation (ie Formulation 6) also has a higher protein loading of 161200.doc -99 - 201233333 and therefore increased emulsion stability. Example 28 In this example, a trace amount was evaluated. Effect of nutrient content on the color of the sterilized dad sterilization formula and the 3-9 day sterile sterilization formula on days 1-2 and 3-9. The color quality of the formula was evaluated using the Aegis color method. The Aegis color method uses spectrophotometry. The percentage of light reflected from the sample is measured from 〇 (black) to 1 〇〇 (white). Bright color infant formula (which is usually preferred by consumers) has a higher Aegean color score, while dark formula has a darker formula. Low score. The low and high micronutrient content of the present invention measured over a plurality of time periods. The Aegean color score of the sterilization dad sterilization and aseptic sterilization formula is set forth in Table 18 below (Sterilization Sterilization Formula) and Table 19 (No. Table 3: Sterilization Sterilization Formulation Energy (kcal/L) Micronutrient Content Time Interval Egson Color Score (%) a Formula 3 (Day 1-2) 250 Still 0 Day 39.3 1 month... 2 months 33.3 4 months 30.2 9 months 28.5 12 months 28.2 Formula 4 (Day 1-2) 250 0 days 44.1 1 month... 3 months 37.5 6 months 35.4 9 months 33.4 12 months 33.0 Formula 1 (Day 1-2) 2 70 Low 0 days 47.9 2 months 43.7 4 months 42.2 6 months 40.3 9 months 38.6 Formula 2 (Day 1-2) 270 Low 0 days 54.4 3 months 49.7 161200.doc •100· 201233333 Formula energy (kcal /L) Micronutrient content time interval Egstrong color score (%) a 6 months 47.8 Formula 8 (Day 3-9) 410 Still 0 days 39.4 Formula 5 (Days 3-9) 406 Low 0 days 51.1 3 Month 48.8 6 months 46.0 Formula 6 (Day 3·9) 406 Low 0 days 45.3 Formula 7 (Day 3-9) 406 Low 0 days 46.2 (---) means untested a for all measurements, Egson color scores were determined using an Agtron M-45 spectrophotometer (blue filter - 43 6 nm). Table 19: Day 3-9 Sterile Sterilization Formulation Energy (kcal/L) Micronutrient Content Time Interval Egson Color Score (%) a Formula 11 410 Still 0 Days 53.1 1 Month 49.7 2 Months... 4 Month... 12 months 46.2 Formula 10 410 South 0 days 56.5 1 month ___ 3 months 51.7 6 months 53.1 9 months 51.4 12 months 47.6 Formula 9 406 Low 0 days 61.5 1 month ___ 2 Month 60.0 6 months 56.9 9 months 53.8 I61200.doc -101- 201233333 (---) means untested a For all measurements, use Agtron M-45 spectrophotometer (blue filter -43 6 nm) Determination of the Aegean color score. As can be seen from these results, the 1-2 days of infant formula with low micronutrient content has higher Egley color than the infant formula of 1-2 days of sterilization with high micronutrient content. Score and therefore have a brighter color appearance. Similar results were obtained on the 3rd-9th Sterilization Sterilization Formulation and the 3-9th Sterile Sterilization Formula, where the low micronutrient content formulation had a higher Egson color score than the comparable formula with high micronutrient content. Even after prolonged periods of time (in some cases up to 9 months after product formulation), color improvements in low micronutrient formulations compared to comparable high micronutrient formulations were observed. These results show that the infant formula of the present invention having a low micronutrient content has a lighter and lighter color appearance than a comparable formulation having a high micronutrient content. Example 29 In this example, the effect of micronutrient content on the particle size distribution of the formulation of the sterilization and sterilization process and the separation rate of the cream were evaluated. Specifically, 'Beckman Coulter LS 13 320 Light Scattering Machine' was used to determine the particle size distribution of the 2nd plate formulation with high micronutrient content (Formulation 3) or low micronutrient content (Formulation 1). The results are shown in Figure 12. As can be seen from Figure 12, the majority of the particles in the low-micronutrient 1st day sterilization sterilizer (Formulation 1) have a size between about 〇·1 μπι and about μ8 μιη. Between 1 μηη and about 8 μπι. Compared to 161200.doc •102·201233333, the particle size distribution of the '1st high-nutrient nutrient 1st day sterilization kettle sterilization formula (Formulation 3) is more evenly in the range of about 〇.i μπ1 to about 7 μπι. The average particle size of each formulation was determined from the particle size distribution and used to calculate the cream separation speed for each formulation. Specifically, the following equation is used to calculate the separation rate of the cream:

Vcream 2 PP particleVcream 2 PP particle

gR2 其中： vcream為乳油分離速度 Pfluid為配方密度gR2 where: vcream is the cream separation speed Pfluid is the formula density

Pparticle為顆粒密度 η為配方黏度 R為平均粒徑 g為重力加速度。 藉由使用Beckman Coulter LS 13 320光散射機器量測單 位樣品（100 mL)中顆粒之總表面積來計算顆粒（例如油滴） 之密度。接著使用超離心法量測附著於油滴表面之蛋白質 之體積。接著用蛋白質體積除以油滴總表面積得到塗於各 油滴上之蛋白質層之平均厚度。接著使用蛋白質密度 1.41(Fischer等人，pr〇tein Science (2004)，第 π (1〇)卷 第2825-2828頁）計算平均顆粒密度。 各配方之R2值及乳油分離速度展示於表2〇中。 161200.doc -103· 201233333 表20:第1-2天殺菌釜滅菌配方之粒徑及乳油分離速度 能量 (kcal/L) 微量營養素含量 平均粒徑之平方 iR2)(_2) 乳油分離速度 (公分/天） 配方1 270 低 1.8 3.2 配方3 250 高 3.5 6.3 如可自此表可見’低微量營養素第卜2天殺菌釜滅菌配 方（配方1)之平均粒徑小於高微量營養素第1_2天殺菌釜滅 菌配方（配方3)之平均粒徑。因為較小粒徑可表示產品穩定 性’因此該等結果顯示本發明之低微量營養素第1 _2天殺 菌釜滅菌配方之產品穩定性大於可比較之具有高微量營養 素含量之配方。 乳油分離速度量測顆粒（例如液滴）移動穿過液體樣品（在 此情況下’嬰兒配方）之速率且預示嬰兒配方形成乳油層 之能力。如可自表20中可見，低微量營養素含量第1-2天 殺菌釜滅菌配方之乳油分離速度小於高微量營養素含量第 1-2天殺菌爸滅菌配方之乳油分離速度。該等結果顯示本 發明之低微量營養素含量第1_2天殺菌釜滅菌配方與可比 較之高微量營養素配方相比形成乳油層之能力降低且因此 物理穩定性改良。 【圖式簡單說明】 圖1為展示如實例16中所論述，與對照全熱量配方及人 乳相比，多種低熱量第1-2天及第3·9天嬰兒配方之緩衝強 度之圖表。 圖2為展示如實例16中所論述，與對照全熱量配方及人 161200.doc •104- 201233333 乳相比’多種低熱量第1-2天及第3-9天嬰兒配方之緩衝能 力之圖表。 圖3為展示如實例17中所論述，與對照全熱量配方相 比，添加HC1對低熱量第1-2天及第3-9天復原粉末嬰兒配 方之pH值之影響之圖表。 圖4為展示如實例17中所論述，與對照全熱量配方相 比，低熱量第1-2天及第3-9天復原粉末嬰兒配方之緩衝強 度之圖表。 圖5為展示如實例17中所論述，與對照全熱量配方相 比’低熱量第1-2天及第3-9天復原粉末嬰兒配方之緩衝能 力（如在向100 mL配方中添加5.5〇毫莫耳HC1後藉由pH值降 低量測）之圖表。 圖6為展示如實例17中所論述，與對照全熱量配方相 比，低熱里第1 -2天及第3-9天復原粉末嬰兒配方之緩衝能 力（如在向100 mL配方中添加5.50毫莫耳Hcl後藉由[H+]增 加量測）之圖表。 圖7為展示如實例2〇中所論述，與對照全熱量配方相 比，在活體外腸_消化後，低熱量第丨_2天及第3_9天復原 粉末嬰兒配方之蛋白質分子量（MW)中值之圖表。 圖8為展示如實例2〇中所論述，與對照全熱量配方相 比，在活體外腸胃消化後，低熱量第丨_2天及第3_9天復原 粉末嬰兒配方中MW大於5000 Da之佔總蛋白質百分比之圖 表。 圖9為展不如實例2〇中所論述，與對照全熱量配方相 161200.doc 201233333 比，在/舌體外腸胃消化後’低熱量第U天及第3_9天復原 粉末嬰兒配方在高速離心後蛋白質顆粒中不可溶（難消化） 蛋白質量之圖表。 圖10為展示如實例23中所論述，與對照全熱量配方相 比，在胰酶消化71分鐘後，低熱量第1-2天及第3_9天復原 粉末嬰兒配方之蛋白質MW中值之圖表。 圖11為展示如實例23中所論述，與對照全熱量配方相 比’在胰酶消化71分鐘後，低熱量第1-2天及第3_9天復原 粉末嬰兒配方中MW大於5000 Da之佔總蛋白質百分比之圖 表。 圖12為展示如實例29中所論述，經殺菌釜滅菌之具有高 微量營養素含量（配方3)或低微量營養素含量（配方1)之第 1-2天配方之粒徑分佈之圖表。 161200.doc • 106-Pparticle is the particle density η is the formula viscosity R is the average particle size g is the gravitational acceleration. The density of particles (e.g., oil droplets) was calculated by measuring the total surface area of the particles in a single sample (100 mL) using a Beckman Coulter LS 13 320 light scattering machine. The volume of protein attached to the surface of the oil droplets was then measured using ultracentrifugation. The average thickness of the protein layer applied to each oil droplet is then obtained by dividing the volume of the protein by the total surface area of the oil droplet. The average particle density was then calculated using protein density 1.41 (Fischer et al., pr〇tein Science (2004), pp. pp. 2825-2828). The R2 values of each formulation and the separation rate of the cream are shown in Table 2〇. 161200.doc -103· 201233333 Table 20: Particle size and cream separation speed energy (kcal/L) of the sterilization solution for the sterilization of the 1-2 days. The square of the average particle size of the micronutrient content iR2)(_2) Separation speed of the cream (cm) /day) Formulation 1 270 Low 1.8 3.2 Formulation 3 250 High 3.5 6.3 As can be seen from this table, the average particle size of the 'low micronutrient bismuth 2 day sterilization sterilizer (formulation 1) is smaller than the high micronutrient 1st day sterilizer The average particle size of the sterilization formulation (Formulation 3). Since the smaller particle size can indicate product stability, the results show that the low micronutrient of the present invention has a product stability greater than that of a comparable high nutrient content. The cream separation rate measures the rate at which particles (e.g., droplets) move through the liquid sample (in this case &apos; infant formula) and predicts the ability of the infant formula to form a cream layer. As can be seen from Table 20, the low micronutrient content on the first 1-2 days, the separation rate of the emulsification formula of the sterilization kettle is less than the high micronutrient content. The emulsification separation speed of the sterilization dad sterilization formula is 1-2 days. These results show that the low micronutrient content of the present invention, the 1st day sterilization autoclave formulation, has a reduced ability to form a cream layer compared to a high micronutrient formulation and thus has improved physical stability. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a graph showing the buffer strength of various low calorie 1-2 and 3rd day infant formulas as compared to the control full calorie formula and human milk as discussed in Example 16. Figure 2 is a graph showing the buffering capacity of a variety of low calorie 1-2 and 3-9 infant formulas as compared to the control full calorie formula and human 161200.doc • 104-201233333 milk as discussed in Example 16. . Figure 3 is a graph showing the effect of the addition of HC1 on the pH of the low calorie 1-2 day and 3-9 day reconstituted powder infant formula as discussed in Example 17. Figure 4 is a graph showing the buffer strength of the low calorie 1-2 day and 3-9 day reconstituted powder infant formula as compared to the control full calorie formulation as discussed in Example 17. Figure 5 is a graph showing the buffering capacity of the 'low calorie 1-2 day and 3-9 day reconstituted powder infant formula as compared to the control full calorie formulation as discussed in Example 17 (e.g., adding 5.5 to a 100 mL formulation) A graph of millimolar HC1 followed by pH reduction measurements). Figure 6 is a graph showing the buffering capacity of the reconstituted powdered infant formula on days 1-2 and days 3-9 in low heat compared to the control full calorie formulation as discussed in Example 17, such as adding 5.50 milligrams to a 100 mL formulation. A graph of the increase in measurement by [H+] after Mohr Hcl. Figure 7 is a graph showing the protein molecular weight (MW) of the reconstituted powder infant formula after in vitro intestinal digestion, low calorie 丨_2 days and 3-9 days compared to the control total calorie formulation as discussed in Example 2A. A chart of values. Figure 8 is a graph showing the MW greater than 5000 Da in the low calorie 丨_2 and 3 _9 reconstituted powder infant formula after in vitro gastrointestinal digestion as compared to the control holistic digestion as discussed in Example 2 总. A graph of the percentage of protein. Figure 9 is not as discussed in Example 2, compared with the control full-calorie formula 161200.doc 201233333, after the in vitro gastrointestinal digestion of the 'lower calorie' U-day and 3_9-day reconstituted powder infant formula after high-speed centrifugation of protein A graph of the insoluble (hard to digest) protein quality in the granules. Figure 10 is a graph showing the median MW of protein in the reconstituted powder infant formula for low calorie days 1-2 and day 3-9 after pancreatin digestion for 71 minutes as compared to the control full calorie formulation as discussed in Example 23. Figure 11 is a graph showing the MW greater than 5000 Da in the reconstituted powder infant formula for low calorie days 1-2 and 3-9 days after pancreatic enzyme digestion for 71 minutes as compared to the control total calorie formulation as discussed in Example 23. A graph of the percentage of protein. Figure 12 is a graph showing the particle size distribution of the formulation of the first 1-2 days of sterilization with a high micronutrient content (Formulation 3) or a low micronutrient content (Formulation 1) as discussed in Example 29. 161200.doc • 106-

Claims (1)

201233333 七、申請專利範圍： 1· 一種改良嬰兒之嬰兒配方耐受性之方法，該方法包含對 該嬰兒投與能量含量為約200至小於600千卡/公升配方之 嬰兒配方。 2·如請求項1之方法，其中該嬰兒為新生兒。 3. 如請求項1之方法，其中該嬰兒配方為能量含量為約200 至約360千卡/公升配方之第1-2天嬰兒配方。 4. 如請求項3之方法’其進一步包含在出生後頭兩天期間 對該嬰兒投與該第1_2天嬰兒配方及在出生後第3至9天對 該嬰兒投與能量含量為約360至小於6〇〇千卡/公升配方之 第3-9天嬰兒配方。 5. 一種改良嬰兒之嬰兒配方耐受性之方法，該方法包含： 對該嬰兒投與低微量營養素嬰兒配方，其包含微量營養 素及至少一種選自由蛋白質 '碳水化合物、脂肪及其組 合組成之群的常量營養素且具有約200至小於600千卡/公 升配方之能量含量，其中以單位體積計，至少65%該等 微里營養素以習知相應微量營養素量之約3 〇%至約8〇% 之量包括於該嬰兒配方中。 6. 如請求項5之方法，其中該嬰兒為新生兒。 7· 一種改良嬰兒之嬰兒配方耐受性之方法，該方法包含： 對該嬰兒投與低微量營養素嬰兒配方，其包含微量營養 素及至少一種選自由蛋白質、碳水化合物、脂肪及其組 合組成之群的常量營養素且具有約200至約360千卡/公升 配方之能量含量，其中以單位體積計，至少45%該等微 161200.doc 201233333 之約30%至約65%之 量營養素以習知相應微量營養素量 量包括於該嬰兒配方中。 8.如請求項7之方法，201233333 VII. Scope of Application: 1. A method for improving the tolerance of an infant's infant formula, which comprises administering to the infant an infant formula having an energy content of from about 200 to less than 600 kcal/liter. 2. The method of claim 1, wherein the infant is a newborn. 3. The method of claim 1, wherein the infant formula is an infant formula of the first 1-2 days of an energy content of from about 200 to about 360 kcal/liter. 4. The method of claim 3, which further comprises administering the infant's Formula 1_2 infant formula during the first two days of life and administering the infant to an energy content of about 360 to less than 3 to 9 days after birth. 3-9 days baby formula for 6 〇〇 kcal / liter formula. 5. A method of improving infant formula tolerance in an infant, the method comprising: administering to the infant a low micronutrient infant formula comprising micronutrients and at least one selected from the group consisting of protein carbohydrates, fats, and combinations thereof a macronutrient having an energy content of from about 200 to less than 600 kcal/liter of formula, wherein at least 65% of the micronutrient nutrient per unit volume is from about 3% to about 8% by weight of a conventional micronutrient. The amount is included in the infant formula. 6. The method of claim 5, wherein the infant is a newborn. 7. A method of improving infant formula tolerance in an infant, the method comprising: administering to the infant a low micronutrient infant formula comprising micronutrients and at least one selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof a macronutrient and having an energy content of from about 200 to about 360 kcal/liter of formula, wherein at least 45% of the micronutrient per unit volume is from about 30% to about 65% of the nutrient of the 161200.doc 201233333 The amount of micronutrient is included in the infant formula. 8. As in the method of claim 7, 其中該嬰兒為新生兒。 其中該嬰兒配方為第1-2天嬰兒配 10.如凊求項9之方法， ’其進一步包含在出生後頭兩天對該 备·兒投與該第1-2天嬰兒配方及在出生後第3至9天對該嬰 兒才又與flb量含量為約36〇至小於6〇〇千卡/公升配方之第3_ 9天嬰兒配方。 11. 如明求項1〇之方法，其中該第3 9天嬰兒配方為低微量營 養素嬰兒配方，其包含微量營養素及至少一種選自由蛋 白質、碳水化合物、脂肪及其組合組成之群的常量營養 素’其中以單位體積計，至少30%該等微量營養素以習 知相應微量營養素量之約55%至約8〇%之量包括於該第3· 9天嬰兒配方中。 12. —種改良嬰兒之嬰兒配方耐受性之方法，該方法包含： 對該嬰兒投與低微量營養素嬰兒配方，其包含微量營養 素及至少一種選自由蛋白質、碳水化合物、脂肪及其組 合組成之群的常量營養素且具有約360至小於600千卡/公 升配方之能量含量’其中以單位體積計，至少30%該等 微量營養素以習知相應微量營養素量之約55%至約8〇% 之量包括於該嬰兒配方中。 13. —種抑制嬰兒胃食道逆流之方法，該方法包含對該嬰兒 投與能量含量為約200至小於600千卡/公升配方之嬰兒配 161200.doc 201233333 方。 種抑制嬰兒胃食道逆流之方法，該方法包含：對該嬰 ，投與低微量營養素嬰兒配方，其包含微量營養素及至 乂種選自由蛋白質、碳水化合物、脂肪及其組合組成 之群的常量營養素且具有約200至小於600千卡/公升配方 里3量其中以單位體積計，至少65。/。該等微量營 養素以習知相應微量營養素量之約30%至約80%之量包 括於該嬰兒配方中。 15·如請求項14之方法，其中該嬰兒為新生兒。 種抑制嬰兒胃食道逆流之方法，該方法包含：對該嬰 兒杈與低微量營養素嬰兒配方，其包含微量營養素及至 &gt; 一種選自由蛋白質、碳水化合物、脂肪及其組合組成 之群的常量營養素且具有約200至約360千卡/公升配方之 月b量含量，其中以單位體積計，至少45%該等微量營養 素以習知相應微量營養素量之約30%至約65%之量包括 於該嬰兒配方中。 17· 一種抑制嬰兒胃食道逆流之方法，該方法包含：對該嬰 兒投與低微量營養素嬰兒配方，其包含微量營養素及至 乂 一種選自由蛋白質、碳水化合物、脂肪及其組合組成 之群的常量營養素且具有約360至小於600千卡/公升配方 之此1含量，其中以單位體積計，至少30%該等微量營 養素以習知相應微量營養素量之約55%至約80%之量包 括於該嬰兒配方中。 18.如請求項17之方法，其中該嬰兒為新生兒。 161200.doc 201233333 19. 20. 如請求項17 法’其中該嬰兒配方為第3-9天嬰兒配 万0 如月长項19之方法，其進__步包含在出生後頭兩天期間 對該嬰兒投與能量含量為約200至約36〇千卡/公升配方之 第1-2天嬰兒配方及在出生後第3至9天對該嬰兒投與該第 3-9天嬰兒配方。 161200.docThe baby is a newborn. Wherein the infant formula is the 1-2 day baby with 10. If the claim item 9 is used, 'it further includes administering the baby 1-2 day infant formula and after birth in the first two days after birth The 3rd to 9th day infant formula for the infant on the 3rd to 9th day with the flb content of about 36 〇 to less than 6 〇〇 kcal / liter. 11. The method of claim 1, wherein the 39th day infant formula is a low micronutrient infant formula comprising micronutrients and at least one macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof Wherein at least 30% of the micronutrient is included in the Day 3.9 infant formula in an amount of from about 55% to about 8% by weight of the conventional micronutrient amount per unit volume. 12. A method of improving infant formula tolerance in an infant, the method comprising: administering to the infant a low micronutrient infant formula comprising micronutrients and at least one selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof a group of macronutrients having an energy content of from about 360 to less than 600 kcal/liter of formula 'of which at least 30% of the micronutrient is from about 55% to about 8% by weight of the conventional micronutrient amount per unit volume The amount is included in the infant formula. 13. A method of inhibiting reflux of the gastroesophage of a baby, the method comprising administering to the infant an infant having an energy content of from about 200 to less than 600 kcal/liter of formula 161200.doc 201233333 square. A method for inhibiting gastroesophageal reflux in a baby, the method comprising: administering to the infant, a low micronutrient infant formula comprising micronutrients and a macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof There are 3 amounts in a formulation of from about 200 to less than 600 kcal/liter, wherein at least 65 per unit volume. /. The micronutrient is included in the infant formula in an amount from about 30% to about 80% of the amount of the corresponding micronutrient. 15. The method of claim 14, wherein the infant is a newborn. A method for inhibiting gastric gastroesophageal reflux in a baby, the method comprising: the infant formula and the low micronutrient infant formula comprising micronutrients and to &gt; a macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof Having a monthly b content of from about 200 to about 360 kcal/liter of formula, wherein at least 45% of the micronutrient per unit volume is included in an amount from about 30% to about 65% of the amount of the corresponding micronutrient In the infant formula. 17. A method of inhibiting gastroesophageal reflux in a baby, the method comprising: administering to the infant a low micronutrient infant formula comprising micronutrients and a macronutrient selected from the group consisting of proteins, carbohydrates, fats, and combinations thereof. And having a content of from about 360 to less than 600 kcal / liter of the formula, wherein at least 30% of the micronutrient is included in the amount of from about 55% to about 80% by weight of the conventional micronutrient amount per unit volume In the infant formula. 18. The method of claim 17, wherein the infant is a newborn. 161200.doc 201233333 19. 20. The method of claim 17 wherein the infant formula is a 3-9 day infant with a 10,000 of a month length item 19, the step __ including the infant during the first two days of life The infant formula of the first 1-2 days of the formulation having an energy content of from about 200 to about 36 kilocalories per liter is administered and the infant formula 3-9 is administered to the infant on days 3 to 9 after birth. 161200.doc