TWI612902B

TWI612902B - Use of a composition for manufacturing an improved intestinal functional composition and preparation method thereof

Info

Publication number: TWI612902B
Application number: TW099141432A
Authority: TW
Inventors: Hisae Kume; Taketo Yamaji
Original assignee: Meiji Co Ltd
Priority date: 2009-11-30
Filing date: 2010-11-30
Publication date: 2018-02-01
Also published as: TW201121430A; JP6158380B2; CN107822150A; JP5946642B2; JPWO2011065552A1; CN102665750A; CN102665750B; WO2011065552A1; HK1246098A1; JP2016172722A

Abstract

使用ConA誘導之小鼠肝炎模型，評估攝取本發明組成物的群對小腸或脾臟中細胞激素的產生與對小腸的傷害。結果顯示，攝取本發明組成物的群，除抑制肝臟及血漿細胞激素的產生上升，也抑制小腸、脾臟中MCP-1或IL-6的產生上升，小腸的組織傷害也減輕。攝取本發明組成物2週後的正常小鼠，測量並評估其小腸重量、大腸重量。結果顯示，小腸重量與大腸重量皆有顯著地增加，且絨毛的平均長度及肌肉層的厚度相對於對照組顯示顯著的高值。 The mouse model of hepatitis induced by ConA was used to evaluate the production of cytokines in the small intestine or spleen and the damage to the small intestine by the group ingesting the composition of the present invention. The results show that the group ingesting the composition of the present invention, in addition to suppressing the production of liver and plasma cytokines, also inhibits the production of MCP-1 or IL-6 in the small intestine and spleen, and the tissue damage of the small intestine is also reduced. Normal mice 2 weeks after ingesting the composition of the present invention, the small intestine weight and large intestine weight were measured and evaluated. The results showed that both the weight of the small intestine and the weight of the large intestine increased significantly, and the average length of the villi and the thickness of the muscle layer showed significantly higher values than the control group.

Description

一種組成物用於製造改善腸道功能組成物的用途及其製備方法Use of composition for manufacturing composition for improving intestinal function and preparation method thereof

本發明係為含有乳蛋白質水解物、源自醱酵乳之蛋白質、脂質及糖類之改善腸道功能的組成物。The present invention is a composition containing a milk protein hydrolysate, a protein derived from fermented milk, lipids, and saccharides to improve intestinal function.

近年來生活習慣病的增加與飲食有重大的關係。攝取必要的營養素對於維持及增進健康是非常重要的，為了有效地消化吸收此營養素，必須維持正常的腸道功能。然而，現實中，混亂的生活習慣、不正常飲食、悲傷與恐懼等的精神障礙等常會引起便秘或下痢等腸道功能異常。若此腸道功能持續異常，則會成為腸病變或癌症等疾病的原因。目前，使用可改善腸道功能之比菲德氏菌或、Lactobacillus乳酸菌(益生菌)的優格或醱酵飲料等，廣泛地作為食品使用。具有可促進腸道內有用微生物增殖之寡糖或食物纖維等的整腸功能之食品也被廣泛利用。然而這些食品僅可改善腸內環境，卻難以促進小腸黏膜的增生及機能的修復，因此亟需開發此類食品。The increase in lifestyle-related diseases in recent years has a significant relationship with diet. Ingesting necessary nutrients is very important for maintaining and improving health. In order to effectively digest and absorb this nutrient, normal intestinal function must be maintained. However, in reality, disordered habits, abnormal diet, mental disorders such as sadness and fear often cause intestinal dysfunction such as constipation or chin. If this intestinal function continues to be abnormal, it can be a cause of diseases such as bowel disease or cancer. Currently, Bifidobacterium or Lactobacillus lactic acid bacteria (probiotics), yoghurt or fermented beverages, which can improve intestinal function, are widely used as food. Foods having an intestinal rectifying function such as oligosaccharides or dietary fiber that can promote the proliferation of useful microorganisms in the intestine are also widely used. However, these foods can only improve the intestinal environment, but it is difficult to promote the proliferation of the intestinal mucosa and the repair of functions. Therefore, the development of such foods is urgently needed.

由臨床的觀點來看，造成小腸功能表面積減少的病變包括腸道切除、放射線照射、腸道缺血或外傷、克隆氏病(Crohn’s disease)或潰瘍性大腸炎等。對於這些病變，需要使已受損的小腸黏膜的修復或代償機能提高的治療。目前已知，麩醯胺酸、n-3系多價不飽和脂肪酸或鋅等特定營養素對此治療非常重要。作為腸道代謝反應能力的促進代謝‧內分泌適應能力、腸黏膜的增殖‧修復能力，必須經過腸道補給‧投予營養素，前提為營養素通過如膽汁‧胰液分泌的生理性腸道內容物。雖然可以中心靜脈營養或高卡路里輸液或完全靜脈營養輸液的方式補給營養，但容易導致小腸黏膜的萎縮以及腸道功能低弱。因此，業界亟需開發對腸道有益之藥劑或食品。雖然目前已開發各種經腸營養食品、具整腸作用之含食物纖維的食品，但至今卻仍未開發可促進小腸絨毛生長、增加肌肉層厚度等維持‧改善腸道功能的藥劑或綜合營養食品。From a clinical point of view, lesions that cause a decrease in the functional surface area of the small intestine include intestinal resection, radiation irradiation, intestinal ischemia or trauma, Crohn's disease, or ulcerative colitis. For these lesions, there is a need for a treatment that improves the repair or compensatory function of the damaged small intestinal mucosa. It is currently known that specific nutrients such as glutamic acid, n-3 polyunsaturated fatty acids, or zinc are very important for this treatment. As an intestinal metabolic response ability to promote metabolism, endocrine adaptability, intestinal mucosal proliferation, and repair ability, nutrients must be supplied through the intestine and nutrients should be administered, provided that the nutrients pass through physiological intestinal contents such as bile and pancreatic juice. Although nutrition can be supplemented by central venous nutrition or high-calorie infusion or complete intravenous nutrition infusion, it can easily lead to atrophy of the small intestinal mucosa and intestinal dysfunction. Therefore, there is an urgent need for the industry to develop pharmaceuticals or foods that are beneficial to the gut. Although various enteral nutritional foods and dietary fiber-containing foods have been developed, so far, no pharmaceutical or comprehensive nutritional food that can promote the growth of the small intestine villi and increase the thickness of muscle layers has been developed. .

【先前技術文獻】[Previous Technical Literature] 【專利文獻】[Patent Literature]

【專利文獻1】WO2004/047556[Patent Document 1] WO2004 / 047556

【專利文獻2】特開2004-99563[Patent Document 2] JP 2004-99563

本發明的目的為提供可維持、改善腸道功能的組成物。或者本發明提供促進小腸絨毛生長之組成物、增加小腸肌肉層厚度之組成物、改善腸道功能之組成物、預防小腸組織損害之組成物，或抗發炎組成物。An object of the present invention is to provide a composition capable of maintaining and improving intestinal function. Alternatively, the present invention provides a composition that promotes growth of the small intestine villi, a composition that increases the thickness of the small intestine muscle layer, a composition that improves intestinal function, a composition that prevents damage to the small intestine tissue, or an anti-inflammatory composition.

本發明人們使用ConA誘導之小鼠肝炎模型，對於攝取本發明組成物群與攝取一般流體食物群，製作組織標本以評估小腸或脾臟中細胞激素的產生與小腸的損害。調查促進細胞激素TNF-α或IL-6的產生與趨化素MCP-1的產生。結果顯示，攝取本發明營養組成物群之肝臟及血漿中細胞激素的產生受到抑制，且小腸、脾臟中MCP-1或IL-6的產生也受到抑制。而且小腸組織的損害減輕(實施例1、2)。The present inventors used a mouse model of hepatitis induced by ConA to prepare tissue samples for ingesting the composition group of the present invention and ingesting general fluid food groups to evaluate the production of cytokines in the small intestine or the spleen and damage to the small intestine. The investigation promotes the production of cytokines TNF-α or IL-6 and the production of chemokine MCP-1. The results showed that the production of cytokines in the liver and plasma was inhibited, and the production of MCP-1 or IL-6 in the small intestine and spleen was also suppressed. In addition, damage to the small intestine tissue was reduced (Examples 1 and 2).

由此結果並無法得知攝取本發明營養組成物對腸道造成何種變化，在正常小鼠攝取2週後測量其小腸重量、大腸重量。製作與評估小腸組織標本。結果顯示，小腸重量與大腸重量有顯著地增加。小腸組織的評估結果顯示，絨毛的數量沒有差異，但絨毛的平均長度與肌肉層的厚度相對於對照組有顯著的高值。由此結果顯示，具有小腸損害的保護作用、促進小腸黏膜上皮或肌肉層的增生(實施例3)。From this result, it is impossible to know what kind of changes the intestinal tract caused by ingestion of the nutritional composition of the present invention, and the weight of the small intestine and the large intestine was measured 2 weeks after ingestion by normal mice. Preparation and evaluation of small intestine tissue specimens. The results showed a significant increase in the weight of the small and large intestines. The evaluation of the small intestine showed that there was no difference in the number of villi, but the average length of villi and the thickness of the muscle layer had significantly higher values compared to the control group. From these results, it was shown that it has a protective effect on the small intestine damage and promotes the proliferation of the small intestinal mucosa epithelium or muscle layer (Example 3).

本發明人們更使用引朵美酒辛(indomethacin)誘導之大鼠小腸損害模型，對於攝取本發明營養組成物群與攝取一般流體食物群，調查腸道通透性指標的酚紅(phenolsulfonphthalein)的尿中***率。進一步由一般的血液檢查肝臟、腸道膜淋巴結的細菌移位(Bacterial Translocation)作檢討。結果顯示，攝取本發明營養組成物群，腸道膜的通透性亢進受到抑制，肝臟或腸道膜磷巴結的細菌移位受到抑制。而且，從一般血液檢查結果，伴隨投予引朵美酒辛(indomethacin)之小腸損害的血中嗜嗜中性球或單核球數目的增加在營養組成物群受到抑制。由上述結果可知，攝取營養組成物具有保護腸道、抑制非固醇類抗發炎藥物等藥物對小腸所造成的傷害、有效預防因腸損害所引起的細菌移位及其所誘發的敗血症或肺炎等感染症、維持免疫系統正常的效果(實施例4)。The present inventors even used a model of intestinal damage induced by indomethacin to investigate the urine of phenolsulfonphthalein, which is an indicator of intestinal permeability, for ingesting the nutritional composition group of the present invention and ingesting general fluid food groups. Medium excretion rate. Bacterial translocation of liver and intestinal membrane lymph nodes was examined by a general blood test. The results showed that ingestion of the nutritional composition group of the present invention inhibited the hyperpermeability of the intestinal membrane, and inhibited the bacterial translocation of phosphorous nodes in the liver or intestinal membrane. In addition, from the results of general blood tests, an increase in the number of neutrophils or monocytes in the blood accompanying the damage to the small intestine of indomethacin was suppressed in the nutrient composition group. From the above results, it can be seen that ingestion of nutritional composition can protect the intestine, inhibit non-sterol anti-inflammatory drugs and other drugs from causing damage to the small intestine, effectively prevent bacterial displacement caused by intestinal damage, and induce sepsis or pneumonia. Effect of waiting for infectious diseases and maintaining normal immune system (Example 4).

本發明人們分析營養組成物中的何種成分與ConA誘導小鼠肝炎模型中所獲知的肝炎抑制作用及小腸損害保護作用或維持腸道功能有關。結果顯示，腸道功能的維持與乳清蛋白質水解物、異麥芽酮糖、夸克(Quark)有關(實施例5)。肝炎抑制作用主要與乳清蛋白質水解物及夸克(Quark)有關(實施例6)。The present inventors analyzed what kind of ingredients in the nutritional composition is related to the hepatitis inhibitory effect and small intestinal damage protection effect or maintenance of intestinal function that are known in the ConA-induced mouse hepatitis model. The results showed that the maintenance of intestinal function was related to whey protein hydrolysate, isomaltulose, and Quark (Example 5). Hepatitis inhibitory effect is mainly related to whey protein hydrolysate and Quark (Example 6).

基於上述發現，本案提供下列發明。Based on the above findings, the present invention provides the following inventions.

[1]促進小腸絨毛生長之組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。[1] Compositions that promote the growth of small intestinal villi, including milk protein hydrolysates as protein and protein derived from fermented milk, fats and oils as lipids, and isomaltulose as sugars.

[2]如[1]所記載之組成物，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[2] The composition according to [1], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[3]如[1]或[2]所記載之組成物，源自醱酵乳之蛋白質係來自於新鮮乳酪。[3] The composition according to [1] or [2], wherein the protein derived from fermented milk is derived from fresh cheese.

[4]使小腸肌肉層厚度增加的組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。[4] A composition for increasing the thickness of the small intestine muscle layer, including milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[5]如[4]所記載之組成物，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[5] The composition according to [4], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[6]如[4]或[5]所記載之組成物，源自醱酵乳之蛋白質係來自於新鮮乳酪。[6] The composition according to [4] or [5], wherein the protein derived from fermented milk is derived from fresh cheese.

[7]改善腸道功能的組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。[7] Compositions for improving intestinal function, including milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[8]如[7]所記載之組成物，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[8] The composition according to [7], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[9]如[7]或[8]所記載之組成物，源自醱酵乳之蛋白質係來自於新鮮乳酪。[9] The composition according to [7] or [8], wherein the protein derived from fermented milk is derived from fresh cheese.

[10]預防小腸組織損害的組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。[10] A composition for preventing damage to small intestine tissue, including milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[11]如[10]所記載之組成物，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[11] The composition according to [10], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[12]如[10]或[11]所記載之組成物，源自醱酵乳之蛋白質係來自於新鮮乳酪。[12] The composition according to [10] or [11], wherein the protein derived from fermented milk is derived from fresh cheese.

[13]抗發炎組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。[13] Anti-inflammatory composition, including milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[14]如[13]所記載之組成物，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[14] The composition according to [13], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[15]如[13]或[14]所記載之組成物，源自醱酵乳之蛋白質係來自於新鮮乳酪。[15] The composition according to [13] or [14], wherein the protein derived from fermented milk is derived from fresh cheese.

[16]促進小腸絨毛生長的方法，包括投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質、作為脂質之油脂、以及作為糖類之異麥芽酮糖的組成物之步驟。[16] A method for promoting the growth of the small intestine villi, comprising the step of administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a sugar.

[17]增加小腸肌肉層厚度的方法，包括投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質、作為脂質之油脂、以及作為糖類之異麥芽酮糖的組成物之步驟。[17] A method for increasing the thickness of the small intestine muscle layer, comprising the step of administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat as a lipid, and an isomaltulose as a sugar.

[18]改善腸道功能的方法，包括投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質、作為脂質之油脂、以及作為糖類之異麥芽酮糖的組成物之步驟。[18] A method for improving intestinal function, comprising the step of administering a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, fats and oils as lipids, and isomaltulose as sugars.

[19]預防小腸組織損害的方法，包括投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質、作為脂質之油脂、以及作為糖類之異麥芽酮糖的組成物之步驟。[19] A method for preventing damage to small intestine tissue, comprising the step of administering a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, fats and oils as lipids, and isomaltulose as sugars.

[20]抑制發炎的方法，包括投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質、作為脂質之油脂、以及作為糖類之異麥芽酮糖的組成物之步驟。[20] A method for suppressing inflammation, comprising the step of administering a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, fats and oils as lipids, and isomaltulose as sugars.

[21]在製造促進小腸絨毛生長之組成物中，使用含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質、作為脂質之油脂、以及作為糖類之異麥芽酮糖的組成物之使用。[21] Use of a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, fat and oil as lipid, and isomaltulose as sugar in manufacturing composition for promoting intestinal villus growth .

[22]在製造使小腸肌肉層厚度增加的組成物中，使用含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質、作為脂質之油脂、以及作為糖類之異麥芽酮糖的組成物之使用。[22] Use of a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a sugar for producing a composition that increases the thickness of the small intestinal muscle layer Its use.

[23]在製造改善腸道功能的組成物中，使用含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質、作為脂質之油脂、以及作為糖類之異麥芽酮糖的組成物之使用。[23] Use of a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a carbohydrate for producing a composition that improves intestinal function. .

[24]在製造預防小腸組織損害的組成物中，使用含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質、作為脂質之油脂、以及作為糖類之異麥芽酮糖的組成物之使用。[24] Use of a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, fat and oil as lipid, and isomaltulose as carbohydrate in a composition for preventing intestinal tissue damage .

[25]在製造抗發炎的組成物中，使用含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質、作為脂質之油脂、以及作為糖類之異麥芽酮糖的組成物之使用。[25] Use of a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a carbohydrate in an anti-inflammatory composition.

[26]用於促進小腸絨毛生長方法之組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。[26] A composition for promoting the growth of small intestinal villi, including milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[27]用於使小腸肌肉層厚度增加方法之組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。[27] The composition for increasing the thickness of the small intestinal muscle layer includes milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[28]用於改善腸道功能的方法之組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。[28] A composition for a method for improving intestinal function, including milk protein hydrolysate of protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[29]用於預防小腸組織損害的方法之組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。[29] A composition for a method for preventing damage to small intestine tissue, including milk protein hydrolysate as protein and protein derived from fermented milk, oil and fat as lipid, and isomaltulose as sugar.

[30]用於抑制發炎的方法之組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。[30] A composition for a method for suppressing inflammation, including a milk protein hydrolysate of protein and protein derived from fermented milk, oils and fats as lipids, and isomaltulose as a sugar.

[31]改善腸道功能的組成物，包括源自醱酵乳之蛋白質。[31] Compositions for improving intestinal function, including protein derived from fermented milk.

[32]改善腸道功能的組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，以及作為糖類之異麥芽酮糖。[32] Compositions for improving intestinal function, including milk protein hydrolysate as protein and protein derived from fermented milk, and isomaltulose as sugar.

[33]如[32]所記載之組成物，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[33] The composition according to [32], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[34]如[31]～[33]任一項所記載之組成物，源自醱酵乳之蛋白質係來自於新鮮乳酪。[34] The composition according to any one of [31] to [33], wherein the protein derived from fermented milk is derived from fresh cheese.

[35]預防小腸組織損害的組成物，包括源自醱酵乳之蛋白質。[35] Composition for preventing damage to small intestine tissue, including protein derived from fermented milk.

[36]預防小腸組織損害的組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，以及作為糖類之異麥芽酮糖。[36] A composition for preventing damage to small intestine tissue, including milk protein hydrolysate as protein and protein derived from fermented milk, and isomaltulose as sugar.

[37]如[36]所記載之組成物，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[37] The composition according to [36], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[38]如[35]～[37]任一項所記載之組成物，源自醱酵乳之蛋白質係來自於新鮮乳酪。[38] The composition according to any one of [35] to [37], wherein the protein derived from fermented milk is derived from fresh cheese.

[39]抗發炎組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質。[39] An anti-inflammatory composition comprising a milk protein hydrolysate as a protein and a protein derived from fermented milk.

[40]如[39]所記載之組成物，更包括作為糖類之異麥芽酮糖。[40] The composition according to [39], further including isomaltulose as a sugar.

[41]如[39]或[40]項所記載之組成物，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[41] The composition according to [39] or [40], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey protein isolate (WPI), alpha-lactoprotein, beta-lactoglobulin, and lactoferrin.

[42]如[39]～[41]任一項所記載之組成物，源自醱酵乳之蛋白質係來自於新鮮乳酪。[42] The composition according to any one of [39] to [41], wherein the protein derived from fermented milk is derived from fresh cheese.

[43]改善腸道功能的方法，包括投予含有源自醱酵乳之蛋白質之組成物的步驟。[43] A method for improving intestinal function, comprising the step of administering a composition containing protein derived from fermented milk.

[44]改善腸道功能的方法，包括投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，以及作為糖類之異麥芽酮糖之組成物的步驟。[44] A method for improving intestinal function, comprising the step of administering a composition containing milk protein hydrolysate as protein, protein derived from fermented milk, and isomaltulose as sugar.

[45]如[44]所記載之方法，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[45] The method according to [44], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey Isolate protein (WPI), alpha-lactoprotein, beta-lactoglobulin and lactoferrin.

[46]如[43]～[45]任一項所記載之方法，源自醱酵乳之蛋白質係來自於新鮮乳酪。[46] The method according to any one of [43] to [45], wherein the protein derived from fermented milk is derived from fresh cheese.

[47]預防小腸組織損害的方法，包括投予含有源自醱酵乳之蛋白質之組成物的步驟。[47] A method for preventing damage to small intestine tissue, comprising the step of administering a composition containing protein derived from fermented milk.

[48]預防小腸組織損害的方法，包括投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質、以及作為糖類之異麥芽酮糖之組成物的步驟。[48] A method for preventing damage to small intestine tissue, comprising the step of administering a composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a sugar.

[49]如[48]所記載之方法，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[49] The method according to [48], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey Isolate protein (WPI), alpha-lactoprotein, beta-lactoglobulin and lactoferrin.

[50]如[47]～[49]任一項所記載之方法，源自醱酵乳之蛋白質係來自於新鮮乳酪。[50] The method according to any one of [47] to [49], wherein the protein derived from fermented milk is derived from fresh cheese.

[51]抑制發炎的方法，包含投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質之組成物的步驟。[51] A method for suppressing inflammation, comprising the step of administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk.

[52]如[51]所記載之方法，組成物含有作為糖類之異麥芽酮糖。[52] The method according to [51], wherein the composition contains isomaltulose as a sugar.

[53]如[51]或[52]任一項所記載之方法，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[53] The method according to any one of [51] or [52], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, and whey protein concentrate (WPC), whey protein isolate (WPI), alpha-lactoprotein, beta-lactoglobulin and lactoferrin.

[54]如[51]～[53]任一項所記載之方法，源自醱酵乳之蛋白質係來自於新鮮乳酪。[54] The method according to any one of [51] to [53], wherein the protein derived from fermented milk is derived from fresh cheese.

[55]源自醱酵乳之蛋白質用於製造改善腸道功能之組成物的使用。[55] The use of fermented milk-derived protein for the production of a composition that improves intestinal function.

[56]乳蛋白質水解物及源自醱酵乳之蛋白質之蛋白質、以及異麥芽酮糖之糖類用於製造改善腸道功能之組成物的使用。[56] Use of a milk protein hydrolysate, a protein derived from fermented milk, and an isomaltulose saccharide for producing a composition that improves intestinal function.

[57]如[56]所記載之使用，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[57] Use as described in [56], milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey Isolate protein (WPI), alpha-lactoprotein, beta-lactoglobulin and lactoferrin.

[58]如[55]～[57]任一項所記載之使用，源自醱酵乳之蛋白質係來自於新鮮乳酪。[58] The use according to any one of [55] to [57], the protein derived from fermented milk is derived from fresh cheese.

[59]源自醱酵乳之蛋白質用於製造預防小腸組織損害的組成物的使用。[59] Use of a protein derived from fermented milk for producing a composition for preventing damage to small intestine tissue.

[60]含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質、以及作為糖類之異麥芽酮糖的組成物之使用，用於製造預防小腸組織損害之組成物。[60] Use of a composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a saccharide, for producing a composition for preventing damage to small intestine tissue.

[61]如[60]所記載之使用，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[61] Use as described in [60], milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey Isolate protein (WPI), alpha-lactoprotein, beta-lactoglobulin and lactoferrin.

[62]如[59]～[61]任一項所記載之使用，源自醱酵乳之蛋白質係來自於新鮮乳酪。[62] The use according to any one of [59] to [61], wherein the protein derived from fermented milk is derived from fresh cheese.

[63]含有乳蛋白質水解物及源自醱酵乳之蛋白質之蛋白質之組成物的使用，用於製造抗發炎組成物。[63] Use of a composition containing a milk protein hydrolysate and a protein derived from fermented milk to produce an anti-inflammatory composition.

[64]如[63]所記載之使用，組成物更包括作為糖類之異麥芽酮糖。[64] The use according to [63], the composition further includes isomaltulose as a sugar.

[65]如[63]或[64]所記載之使用，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[65] Use as described in [63] or [64], milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC) ), Whey Protein Isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[66]如[63]～[65]任一項所記載之使用，源自醱酵乳之蛋白質係來自於新鮮乳酪。[66] The use according to any one of [63] to [65], the protein derived from fermented milk is derived from fresh cheese.

[67]含源自醱酵乳之蛋白質之組成物，使用於改善腸道功能的方法。[67] A composition containing fermented milk-derived protein, used to improve intestinal function.

[68]含有乳蛋白質水解物及源自醱酵乳之蛋白質之蛋白質、以及異麥芽酮糖之糖類的組成物，使用於改善腸道功能的方法。[68] A composition containing a milk protein hydrolysate, a protein derived from fermented milk, and an isomaltulose saccharide, which is used for a method for improving intestinal function.

[69]如[68]所記載之使用，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[69] Use as described in [68], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey Isolate protein (WPI), alpha-lactoprotein, beta-lactoglobulin and lactoferrin.

[70]如[67]～[69]任一項所記載之組成物，源自醱酵乳之蛋白質係來自於新鮮乳酪。[70] The composition according to any one of [67] to [69], wherein the protein derived from fermented milk is derived from fresh cheese.

[71]含源自醱酵乳之蛋白質之組成物，使用於預防小腸組織損害的方法中。[71] A composition containing protein derived from fermented milk, used in a method for preventing damage to small intestine tissue.

[72]含有乳蛋白質水解物及源自醱酵乳之蛋白質之蛋白質、以及異麥芽酮糖之糖類的組成物，使用於預防小腸組織損害的方法。[72] A composition containing a milk protein hydrolysate, a protein derived from fermented milk, and a sugar of isomaltulose for use in a method for preventing damage to small intestine tissue.

[73]如[72]所記載之組成物，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[73] The composition according to [72], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), milk Whey protein isolate (WPI), α-lactoprotein, β-lactoglobulin and lactoferrin.

[74]如[71]～[73]任一項所記載之組成物，源自醱酵乳之蛋白質係來自於新鮮乳酪。[74] The composition according to any one of [71] to [73], wherein the protein derived from fermented milk is derived from fresh cheese.

[75]含有乳蛋白質水解物及源自醱酵乳之蛋白質之組成物，使用於抑制發炎的方法。[75] A composition containing a milk protein hydrolysate and a protein derived from fermented milk, and used to suppress inflammation.

[76]如[75]所記載之組成物，更包括作為糖類之異麥芽酮糖。[76] The composition according to [75], further including isomaltulose as a sugar.

[77]如[75]或[76]所記載之組成物乳，乳蛋白質係擇自於下列所組成之族群：酪蛋白、乳蛋白質濃縮物(MPC)、乳清蛋白、乳清蛋白濃縮物(WPC)、乳清分離蛋白(WPI)、α-乳蛋白、β-乳球蛋白及乳鐵蛋白。[77] The composition milk according to [75] or [76], the milk protein is selected from the group consisting of casein, milk protein concentrate (MPC), whey protein, whey protein concentrate (WPC), whey protein isolate (WPI), alpha-lactoprotein, beta-lactoglobulin, and lactoferrin.

[78]如[75]～[77]任一項所記載之組成物，源自醱酵乳之蛋白質係來自於新鮮乳酪。[78] The composition according to any one of [75] to [77], wherein the protein derived from fermented milk is derived from fresh cheese.

本發明係提供促進小腸絨毛生長之組成物，其含有作為蛋白質之乳蛋白質水解物與源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。The present invention provides a composition for promoting villus growth in the small intestine, which contains a milk protein hydrolysate as a protein, a protein derived from fermented milk, a fat and oil as a lipid, and isomaltulose as a saccharide.

小腸絨毛的生長為促進小腸上皮細胞的增殖。小腸絨毛生長判斷可促進營養的吸收，或促進小腸損害的修復。因此，本發明之組成物可作為例如「小腸絨毛生長劑」、「小腸上皮細胞增殖劑」、「營養吸收促進劑」、「小腸損害修復促進劑」。上述本發明之組成物可用於改善正常人的小腸機能，改善營養不良之高齡者的營養狀態，維持呼吸、循環、代謝等重度機能不全患者(ICU患者)的腸道功能，維持具有腦/神經損害而吞嚥困難患者的營養補給與腸道功能，改善潰瘍性大腸炎或克隆氏病等慢性腸病患者的腸道功能與營養狀態，改善慢性閉塞性肺疾患(COPD)的腸道功能與營養狀態，或改善癌症患者等因抗生素或抗癌藥物所致腸道損害的腸道功能與營養狀態。The growth of the small intestine villi is to promote the proliferation of small intestinal epithelial cells. Small intestinal villi growth judgment can promote the absorption of nutrients, or promote the repair of small intestine damage. Therefore, the composition of the present invention can be used, for example, as a "small intestinal villus growth agent", a "small intestinal epithelial cell proliferation agent", a "nutritional absorption enhancer", and a "small intestine damage repair enhancer". The composition of the present invention can be used to improve the small intestine function of normal people, improve the nutritional status of elderly people who are malnourished, maintain the intestinal function of patients with severe insufficiency such as breathing, circulation and metabolism (ICU patients) and maintain brain / nerve Nutritional supplement and intestinal function in patients with dysphagia and dysphagia, improvement of intestinal function and nutritional status in patients with chronic bowel disease such as ulcerative colitis or Crohn's disease, and improvement of intestinal function and nutrition in chronic obstructive pulmonary disease (COPD) Condition, or improve intestinal function and nutritional status of intestinal damage caused by antibiotics or anticancer drugs, such as cancer patients.

本發明提供可增加小腸肌肉厚度的組成物，其含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。The present invention provides a composition capable of increasing the thickness of the small intestine muscle, comprising a milk protein hydrolysate as a protein, a protein derived from fermented milk, a fat and oil as a lipid, and isomaltulose as a sugar.

小腸肌肉層厚度的增加判斷可促進小腸、大腸的蠕動。小腸肌肉層厚度的增加判斷可促進整腸作用。因此本發明之組成物可作為例如「小腸肌肉層厚度增加劑」、「腸蠕動運動促進劑」、「整腸劑」。上述本發明之組成物可用於改善正常人的小腸功能，改善營養不良之高齡者的營養狀態，維持呼吸、循環、代謝等重度機能不全患者(ICU患者)的腸道功能，維持具有腦/神經損害而吞嚥困難患者的營養補給與腸道功能，改善潰瘍性大腸炎或克隆氏病等慢性腸病患者的腸道功能與營養狀態，改善慢性閉塞性肺疾患(COPD)的腸道功能與營養狀態，或改善癌症患者等因抗生素或抗癌藥物所致腸道損害的腸道功能與營養狀態。It is judged that the thickness of the small intestine muscle layer can promote the peristalsis of the small and large intestines. The increase in the thickness of the small intestine muscle layer is judged to promote intestinal remodeling. Therefore, the composition of the present invention can be used, for example, as an "intestinal muscle layer thickness increasing agent", an "intestinal peristaltic motion promoting agent", and an "intestine regulating agent". The composition of the present invention can be used to improve the small intestine function of normal people, improve the nutritional status of elderly people who are malnourished, maintain the intestinal function of patients with severe dysfunction such as breathing, circulation and metabolism (ICU patients) and maintain brain / nerve Nutritional supplement and intestinal function in patients with dysphagia and dysphagia, improvement of intestinal function and nutritional status in patients with chronic bowel disease such as ulcerative colitis or Crohn's disease, and improvement of intestinal function and nutrition in chronic obstructive pulmonary disease (COPD) Condition, or improve intestinal function and nutritional status of intestinal damage caused by antibiotics or anticancer drugs, such as cancer patients.

本發明提供改善腸道功能之組成物，其含有源自醱酵乳之蛋白質。本發明提供改善腸道功能之組成物，其含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。The present invention provides a composition for improving intestinal function, which contains protein derived from fermented milk. The present invention provides a composition for improving intestinal function, comprising a milk protein hydrolysate as a protein, a protein derived from fermented milk, a fat and oil as a lipid, and isomaltulose as a sugar.

本發明提供改善腸道功能之組成物，其含有為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，以及作為糖類之異麥芽酮糖。The present invention provides a composition for improving intestinal function, comprising a milk protein hydrolysate which is a protein, a protein derived from fermented milk, and isomaltulose as a sugar.

腸道功能的改善係指促進所攝取的營養消化吸收，以及藉由腸道的蠕動促進廢物的***。腸道功能低落常會導致包含腸道淋巴組織(GALT)脆弱化的障壁破壞、細菌移位(BT)或敗血症等發生等，並使得生物體防禦能力下降。腸道功能降低會導致營養不良，並使得調節生物體機能之消化道激素(荷爾蒙)或神經傳導物質的生成/分泌不良。本發明中所述之「腸」包含「小腸」及「大腸」。The improvement of intestinal function refers to the promotion of digestion and absorption of nutrients ingested, and the excretion of waste through the peristalsis of the intestine. Intestinal dysfunction often results in the destruction of the barrier, including bacterial fragility of the intestinal lymphatic tissue (GALT), bacterial translocation (BT), or sepsis, etc., and reduces the defense ability of the organism. Decreased intestinal function leads to malnutrition and poor production / secretion of gastrointestinal hormones (hormones) or neurotransmitters that regulate biological functions. The "intestine" in the present invention includes a "small intestine" and a "large intestine".

因此，本發明之改善腸道功能的組成物可促進消化吸或整腸，可作為例如「腸道功能改善劑」、「消化吸收促進劑」、「整腸劑」、「廢物***促進劑」「腸道免疫改善劑」。Therefore, the composition for improving intestinal function of the present invention can promote digestion and digestion, and can be used as, for example, "intestinal function improving agent", "digestion and absorption promoting agent", "intestinal regulating agent", "waste excretion promoting agent" "Intestinal immune improver".

腸道免疫係指發生於腸道的免疫反應。免疫反應又稱為免疫學的反應。在抗原(非自己)進入生物體時，會引發生物上的各種反應以產生專一性與此抗原反應的抗體或具特異性免疫力的白血球(致敏淋巴細胞)。可稱為針對入侵之抗原所產生一系列的生物免疫反應。Intestinal immunity refers to the immune response that occurs in the intestine. Immune response is also called immunological response. When an antigen (other than itself) enters an organism, it triggers various biological reactions to produce antibodies or white blood cells (sensitized lymphocytes) with specific immunity to this antigen. It can be called a series of biological immune response to the invading antigen.

由於消化道為容易與外界異物接觸的器官，淋巴球包圍以小腸為中心的腸道周圍，吞噬腸道中成為病原體之食物中的病毒或經消化酵素所分解的外源蛋白。因為阻止吸收這些物質，腸道為生物體最初進化的重要免疫組織。例如消化道的機能降低之一的腸道免疫力下降。腸道免疫的降低係指排除外來入侵之病毒等異物(即抗原)、癌細胞等體內發生之異常細胞(即抗原)、或廢物(即抗原)的免疫反應作用降低，在腸道中引起的各種疾病增加，導致延遲治癒。腸道免疫力的改善即為改善這些因腸道免疫力下降所引起的症狀。Because the digestive tract is an organ that is easy to contact with foreign bodies, the lymph ball surrounds the small intestine as the center of the intestine, engulfing the virus in the intestinal tract, or the foreign protein broken down by digestive enzymes. Because the absorption of these substances is prevented, the intestine is an important immune tissue that the organism originally evolved. For example, one of the functions of the digestive tract is reduced intestinal immunity. Decreased intestinal immunity refers to the reduction of immune response of abnormal cells (i.e., antigens) or waste (i.e., antigens) that occur in the body such as foreign viruses (i.e. antigens), cancer cells, etc. Increased disease leads to delayed healing. Improved intestinal immunity is to improve these symptoms caused by decreased intestinal immunity.

上述本發明之組成物可用於改善正常人的小腸機能，改善營養不良之高齡者的營養狀態，維持呼吸、循環、代謝等重度機能不全患者(ICU患者)的腸道功能，維持具有腦/神經損害而吞嚥困難患者的營養補給與腸道功能，改善潰瘍性大腸炎或克隆氏病等慢性腸病患者的腸道功能與營養狀態，改善慢性閉塞性肺疾患(COPD)的腸道功能與營養狀態，或改善癌症患者等因抗生素或抗癌藥物所致腸道損害的腸道功能與營養狀態。The composition of the present invention can be used to improve the small intestine function of normal people, improve the nutritional status of elderly people who are malnourished, maintain the intestinal function of patients with severe insufficiency such as breathing, circulation and metabolism (ICU patients) and maintain brain / nerve Nutritional supplement and intestinal function in patients with dysphagia and dysphagia, improvement of intestinal function and nutritional status in patients with chronic bowel disease such as ulcerative colitis or Crohn's disease, and improvement of intestinal function and nutrition in chronic obstructive pulmonary disease (COPD) Condition, or improve intestinal function and nutritional status of intestinal damage caused by antibiotics or anticancer drugs, such as cancer patients.

本發明提供可預防小腸組織損害之組成物，其含有源自醱酵乳之蛋白質。本發明提供可預防小腸組織損害之組成物，其含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖的組成物。The present invention provides a composition for preventing damage to small intestine tissue, which contains protein derived from fermented milk. The present invention provides a composition capable of preventing damage to small intestine tissue, comprising a milk protein hydrolysate as a protein, a protein derived from fermented milk, a fat and oil as a lipid, and a composition of isomaltulose as a saccharide.

本發明提供可預防小腸組織損害之組成物，其含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，以及作為糖類之異麥芽酮糖的組成物。The present invention provides a composition capable of preventing damage to small intestine tissue, comprising a milk protein hydrolysate as a protein, a protein derived from fermented milk, and a composition of isomaltulose as a sugar.

小腸組織損害可為腸道中癌或潰瘍等，或癌症患者等因服用抗生素或抗癌藥劑等而破壞絨毛或黏膜肌肉層等組織所造成的損害。上述本發明之組成物可用於預防此種小腸組織損害。本發明中所述之「損害」包括「功能無法充分發揮」、「外部損傷」、「傷害」等廣義解釋。Small intestinal tissue damage can be caused by cancer or ulcers in the intestine, or damage caused by villi or mucosal muscle layers caused by cancer patients and other antibiotics or anticancer agents. The composition of the present invention described above can be used to prevent such small intestinal tissue damage. The "damage" in the present invention includes a broad interpretation such as "inability to fully function", "external damage", "injury" and the like.

上述本發明之組成物具有促進絨毛修復作用，或促進黏膜肌肉層修復作用，可作為例如，「小腸組織損害之預防劑」、「絨毛修復促進劑」、「黏膜肌肉層修復促進劑」。The above-mentioned composition of the present invention has a function to promote villus repair or a mucosal muscle layer repair, and can be used, for example, as a "preventive agent for small intestinal tissue damage", "vill repair repair agent", and "mucosal muscle layer repair promoter".

上述本發明之組成物可改善潰瘍性大腸炎或克隆氏病等慢性腸病患者的腸道功能與營養狀態，改善癌症患者等因抗生素或抗癌藥物所致腸道損害的腸道功能與營養狀態。The composition of the present invention can improve the intestinal function and nutritional status of patients with chronic bowel disease such as ulcerative colitis or Crohn's disease, and improve the intestinal function and nutrition of intestinal damage caused by antibiotics or anticancer drugs, such as cancer patients. status.

本發明提供抗發炎組成物，其含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。The present invention provides an anti-inflammatory composition comprising a milk protein hydrolysate as a protein, a protein derived from fermented milk, oils and fats as lipids, and isomaltulose as a sugar.

本發明提供抗發炎組成物，其含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質。The present invention provides an anti-inflammatory composition comprising a milk protein hydrolysate as a protein and a protein derived from fermented milk.

本發明之抗發炎組成物具有抑制潰瘍性大腸炎或克隆氏病等慢性腸病患者之發炎作用。抗發炎作用為抑制發炎性細胞激素的產生之作用，同時藉由抑制與單核球或T細胞組織浸潤有關之MCP-1的生成來抑制發炎的持續或進行。MCP-1，又稱為MCAF(monocyte chemotactic and activating factor)，被視為單核球的趨化因子。對單核球的作用不僅加強趨化性，也可促進溶酶體酵素或活性氧的釋放、增強抗腫瘍活性、以及誘發IL-1及IL-6的產生，目前已非常清楚作為單核球活性因子的角色。除單核球之外，也促進嗜鹼性球化學傳導物質的遊離及T細胞的趨化活性。MCP-1的產生、分泌認為是藉由LPS或發炎性細胞激素刺激生物體中的各種細胞，其中以單核/巨噬細胞、纖維母細胞或血管內皮細胞為代表。已觀察到某種腫瘤細胞可持續地產生MCP-1(不需藉由其他刺激因子)。現今的研究成果可知，MCP-1與動脈硬化、延遲型過敏、類風濕關節炎、或肺病等各種發炎性疾病中單核球及T細胞的組織浸潤有關。The anti-inflammatory composition of the present invention has the effect of inhibiting the inflammation of patients with chronic intestinal diseases such as ulcerative colitis or Crohn's disease. The anti-inflammatory effect is to inhibit the production of inflammatory cytokines, and at the same time to suppress the persistence or progress of inflammation by inhibiting the production of MCP-1 related to the infiltration of monocytes or T cell tissues. MCP-1, also known as MCAF (monocyte chemotactic and activating factor), is considered as a chemokine for mononuclear spheres. The effect on mononuclear spheres not only strengthens chemotacticity, but also promotes the release of lysosomal enzymes or reactive oxygen species, enhances anti-tumor activity, and induces the production of IL-1 and IL-6. It is now very clear that mononuclear spheres The role of active factors. In addition to mononuclear spheres, it also promotes the release of basophilic chemically conductive substances and the chemotactic activity of T cells. The production and secretion of MCP-1 are thought to stimulate various cells in the organism by LPS or inflammatory cytokines, including monocytes / macrophages, fibroblasts, or vascular endothelial cells. It has been observed that certain tumor cells can continuously produce MCP-1 (without the need for other stimulating factors). Today's research results show that MCP-1 is associated with tissue infiltration of monocytes and T cells in various inflammatory diseases such as arteriosclerosis, delayed allergies, rheumatoid arthritis, or lung disease.

本發明之抗發炎組成物為具有抗發炎或減輕組織損害的作用，可作為例如「抗發炎劑」、「組織損害減輕劑」。The anti-inflammatory composition of the present invention has an effect of anti-inflammatory or reducing tissue damage, and can be used as, for example, "anti-inflammatory agent" or "tissue damage reducing agent".

上述本發明之組成物可維持呼吸、循環、代謝等重度機能不全患者(ICU患者)的腸道功能，維持具有腦/神經損害而吞嚥因難患者的營養補給與腸道功能，改善潰瘍性大腸炎或克隆氏病等慢性腸病患者的腸道功能與營養狀態，改善慢性閉塞性肺疾患(COPD)的腸道功能與營養狀態，或改善癌症患者等因抗生素或抗癌藥物所致腸道損害的腸道功能與營養狀態。The composition of the present invention can maintain the intestinal function of patients with severe insufficiency (ICU patients) such as breathing, circulation and metabolism, maintain the nutritional supply and intestinal function of patients with brain / nerve damage and difficulty swallowing, and improve ulcerative large intestine Intestinal function and nutritional status in patients with chronic bowel disease such as inflammation or Crohn's disease, improve intestinal function and nutritional status of chronic obstructive pulmonary disease (COPD), or improve intestinal tract caused by antibiotics or anticancer drugs, such as cancer patients Impaired gut function and nutritional status.

以下說明本發明上述各組成物中所含的有效成分。Hereinafter, the active ingredients contained in the above-mentioned compositions of the present invention will be described.

本發明之組成物含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質。The composition of the present invention contains a milk protein hydrolysate as a protein and a protein derived from fermented milk.

本發明之乳蛋白質水解物係擇自於酪蛋白、乳蛋白質濃縮物(Milk Protein Concentrate:MPC)、總乳蛋白質(Total Milk Protein)=TMP)、乳清、乳清蛋白、乳清蛋白濃縮物(Whey Protein Concentrate:WPC)、乳清分離蛋白(Whey Protein Isolate:WPI)、α-乳蛋白(α-La)、β-乳球蛋白(β-Lg)及乳鐵蛋白水解物。The milk protein hydrolysate of the present invention is selected from casein, milk protein concentrate (MPC), total milk protein (TMP), whey, whey protein, whey protein concentrate (Whey Protein Concentrate: WPC), Whey Protein Isolate (WPI), α-lactoprotein (α-La), β-lactoglobulin (β-Lg), and lactoferrin hydrolysate.

乳蛋白質的定義、分類及製法可參照日本食品科學，1989年7月號，p42～48他，或牛奶綜合辭典，1992年1月20日，編者：山內邦男，橫山謙吉編集，朝倉書店發行。For the definition, classification and manufacturing method of milk protein, please refer to Japanese Food Science, July 1989, p42 ～ 48, or the Milk Comprehensive Dictionary, January 20, 1992. Editor: Yamanouchi, edited by Kenji Yokoyama, Asakura Bookstore issued.

酪蛋白為以牛乳等之主要蛋白質與磷酸共價結合之磷蛋白質的1種。酪蛋白在牛乳中佔約3%、人乳中佔約0.9%，牛乳中蛋白質佔約80%。Casein is a type of phosphoprotein in which the main protein such as milk is covalently bonded to phosphate. Casein accounts for approximately 3% of cow's milk, approximately 0.9% of human milk, and approximately 80% of protein in cow's milk.

乳清為去除牛乳中的脂肪、酪蛋白、脂溶性維生素等後所殘留的水溶性成分。乳清一般為製造天然乳乳酪或凝乳酶酪蛋白(rennet casein)所得之乳酪乳清或凝乳酶乳清(又稱為甜(甜性)乳清)副產物，從脫脂乳源製造酸性酪蛋白或夸克(Quark)時所獲得之酪蛋白乳清、脫脂凝乳乳清(又稱為酸性(酸)乳清)。乳清的主成分為蛋白質(β-乳球蛋白、α-乳清蛋白等)、乳糖、水溶性維生素、鹽類(礦物成分)，其各自的特徵已清楚於對乳清成分及對牛乳成分的研究中。Whey is a water-soluble component remaining after removing fat, casein, fat-soluble vitamins and the like from cow's milk. Whey is generally a by-product of cheese whey or rennet casein (also known as sweet (sweet) whey) by-products made from natural milk cheese or rennet casein, which produces acidity from skim milk sources Casein or quark (casein whey, skimmed whey) (also known as acidic (acid) whey). The main components of whey are protein (β-lactoglobulin, α-whey protein, etc.), lactose, water-soluble vitamins, and salts (mineral components). Their respective characteristics have been clearly defined for whey components and for milk components. Research.

乳清蛋白包括，例如牛乳中去除酪蛋白後蛋白質的總稱。乳清蛋白由β-乳球蛋白、α-乳蛋白、乳鐵蛋白等複數個成分所構成，但不含有乳糖、維生素、礦物等。在調整牛奶等乳原料呈酸性時，沈殿的蛋白質為酪蛋白，不沈殿的蛋白質為乳清蛋白。Whey protein includes, for example, a general term for protein that has been removed from casein in cow's milk. Whey protein is composed of multiple components such as β-lactoglobulin, α-lactoprotein, and lactoferrin, but does not contain lactose, vitamins, minerals, and the like. When the milk ingredients such as milk are adjusted to be acidic, the protein of Shen Dian is casein, and the protein of Shen Dian is whey protein.

「乳清相關製品」係指乳清經濃縮處理後之濃縮乳清，乳清經乾燥處理後之乳清粉末、乳清之主要蛋白質等經超過濾法(Ultrafiltration：UF)等濃縮處理後，乾燥處理所得之乳清蛋白濃縮物(Whey Protein Concentrate：以下簡稱為「WPC」)，乳清經微過濾(Microfiltration：MF)法或離心分離法等去除脂肪後，以UF法濃縮處理後，經乾燥處理所得之脫脂WPC(低脂肪‧高蛋白質)，乳清的主要蛋白質等經離子交換樹脂法或凝膠過濾法等選擇性分層處理後，乾燥處理所得之乳清分離蛋白(Whey Protein Isolate：以下簡稱為「WPI」)，經奈米過濾法(Nanofiltration：NF)或電透析法等脫鹽處理後，乾燥處理所得之脫鹽乳清，乳清衍生的礦物質成分經沈殿處理後，以離心分離法等濃縮處理所得之礦物質濃縮乳清等。在這些之中，含有乳蛋白乾重(固態成分)15%～80%的WPC作為蛋白質濃縮乳清粉末，根據平成10年3月30日修改的乳等省令，定義為乳製品(濃縮乳清、乳清粉末、WPC、乳清蛋白質濃縮粉末，為經乳品條令規定之製程所獲得者，不論是否有脫鹽步驟)。"Whey-related products" means concentrated whey after whey has been concentrated, whey powder after whey has been dried, and main proteins of whey after being subjected to concentration treatment such as ultrafiltration (UF). The dried whey protein concentrate (Whey Protein Concentrate: hereinafter referred to as "WPC"), whey is removed by microfiltration (MF) method or centrifugal separation method, etc., and then concentrated by UF method. Whey Protein Isolate (Whey Protein Isolate) : Hereinafter referred to as "WPI"), after desalting treatment such as nanofiltration (NF) or electrodialysis, the desalted whey obtained by drying treatment, and the mineral components derived from whey are treated by Shen Dian and centrifuged Mineral concentrate whey, etc. obtained by concentration processing such as separation method. Among these, WPC containing 15% to 80% of dry weight of milk protein (solid content) as protein concentrated whey powder is defined as dairy products (concentrated whey according to provincial ordinances such as milk as amended on March 30, 2010). , Whey powder, WPC, Whey protein concentrated powder, are obtained through the process specified in the dairy regulations, regardless of whether there is a desalination step).

脫脂乳經MF法或UF法等濃縮處理後，乾燥處理所得之乳蛋白質濃縮物(Milk Protein Concentrate：以下簡稱為「MPC」)，與WPC或WPI相同，若降低乳糖或鹽類等的含量，則酪蛋白或乳清蛋白的含量會相對增加。After the skim milk is concentrated by the MF method or the UF method and dried, the milk protein concentrate (Milk Protein Concentrate: hereinafter referred to as "MPC") is the same as WPC or WPI. If the content of lactose or salts is reduced, The casein or whey protein content will increase relatively.

濃縮處理可使用一般的裝置或方法來完成，例如，使用真空蒸發器(evaporator)、真空釜、薄膜垂直上昇管狀型濃縮機、薄膜垂直下降管狀型濃縮機、板狀型濃縮機等，使用減壓下加熱的方法。乾燥處理也可使用一般的裝置或方法來完成，例如，可使用噴霧乾燥(Spray Dryer)法、滾筒乾燥法、冷凍真空乾燥(Freeze Dryer)法、真空(減壓)乾燥法等。Concentration processing can be performed using a common device or method, for example, using a vacuum evaporator, vacuum kettle, thin film vertical upward tube type thickener, thin film vertical downward tube type thickener, plate type thickener, etc. Depressed heating method. The drying process can also be performed using a general device or method. For example, a spray drying method, a drum drying method, a freeze-drying method, a vacuum (decompression) drying method, or the like can be used.

乳蛋白質濃縮物(MPC)的標準製造方法如下所示。The standard manufacturing method of milk protein concentrate (MPC) is shown below.

(1)經膜分離脫脂乳後，濃縮的階段；或(1) after the skim milk is separated through the membrane, the stage of concentration; or

(2)經膜分離脫脂乳後，濃縮、乾燥的階段。(2) After the skim milk is separated through the membrane, it is concentrated and dried.

乳清蛋白濃縮物(WPC)為將乳清的主要蛋白等經超過濾法(Ultrafiltration：UF)等濃縮處理後，乾燥處理所獲得。一般來說，約25%以上的固態成分為乳清蛋白者的總稱。若乳清中的乳糖或鹽類等減少，乳清蛋白的含量相對增加，可獲得約25%～約80%的固態成分。特別是，依據乳等省令，含有以乳蛋白質乾重15%～80%的WPC，定義為蛋白濃縮乳清粉末。The whey protein concentrate (WPC) is obtained by subjecting the main protein of whey and the like to an ultrafiltration (UF) method, followed by a drying treatment. Generally, about 25% of the solids are collectively referred to as those with whey protein. If lactose or salt in whey is reduced, the content of whey protein is relatively increased, and a solid component of about 25% to about 80% can be obtained. In particular, according to provincial regulations such as milk, WPC containing 15% to 80% of the dry weight of milk protein is defined as protein concentrated whey powder.

乳清蛋白濃縮物(WPC)的標準製造方法如下所示。The standard manufacturing method of whey protein concentrate (WPC) is shown below.

(1)經膜分離乳清後，濃縮的階段；或(1) the stage of concentration after whey separation through the membrane; or

(2)經膜分離乳清後，濃縮、乾燥的階段。(2) After the whey is separated through the membrane, it is concentrated and dried.

濃縮處理可使用一般的裝置或方法來完成，例如，可使用真空蒸發器(evaporator)、真空釜、薄膜垂直上昇管狀型濃縮機、薄膜垂直下降管狀型濃縮機、板狀型濃縮機等，使用減壓下加熱方法。乾燥處理也可使用一般的裝置或方法來完成，例如，可使用噴霧乾燥(Spray Dryer)法、滾筒乾燥法、冷凍真空乾燥(Freeze Dryer)法、真空(減壓)乾燥法等。The concentration process can be performed using a general device or method. For example, a vacuum evaporator, a vacuum kettle, a thin film vertical rising tube type thickener, a thin film vertical falling tube type thickener, a plate type thickener, etc. can be used. Heating method under reduced pressure. The drying process can also be performed using a general device or method. For example, a spray drying method, a drum drying method, a freeze-drying method, a vacuum (decompression) drying method, or the like can be used.

乳清蛋白分離物(WPI)為將乳清的主要蛋白質等經離子交換樹脂或電透析法等濃縮處理後，經乾燥處理所獲得。一般來說，固態成分約85%～約95%為乳清蛋白者的總稱。若乳清中的乳糖或鹽類等減少，乳清蛋白的含量會相對增加，可獲得固態成分約90%(85%～95%)。Whey protein isolate (WPI) is obtained by concentrating a main protein of whey and the like through an ion exchange resin or an electrodialysis method and then subjecting it to a drying treatment. Generally speaking, about 85% to 95% of the solid content is the general name of those who have whey protein. If lactose or salt in whey is reduced, the content of whey protein will be relatively increased, and a solid content of about 90% (85% to 95%) can be obtained.

乳清蛋白濃縮物(WPI)的標準製造方法如下所示。The standard manufacturing method of whey protein concentrate (WPI) is shown below.

(1)經膜分離、離子交換樹脂處理或電透析處理乳清後，濃縮的階段；或(1) the stage where the whey is concentrated after membrane separation, ion exchange resin treatment or electrodialysis treatment; or

(2)經膜分離、離子交換樹脂處理或電透析處理乳清後，濃縮、乾燥的階段。(2) After the whey is separated by membrane separation, ion exchange resin treatment, or electrodialysis, it is concentrated and dried.

濃縮處理可使用一般的裝置或方法來完成，例如，可使用真空蒸發器(evaporator)、真空釜、薄膜垂直上昇管狀型濃縮機、薄膜垂直下降管狀型濃縮機、板狀型濃縮機等，減壓下加熱方法。乾燥處理也可使用一般的裝置或方法來完成，例如，可使用噴霧乾燥(Spray Dryer)法、滾筒乾燥法、冷凍真空乾燥(Freeze Dryer)法、真空(減壓)乾燥法等。Concentration processing can be performed using a common device or method. For example, a vacuum evaporator, a vacuum kettle, a thin film vertical upward tube type thickener, a thin film vertical downward tube type thickener, a plate type thickener, etc. can be used. Press the heating method. The drying process can also be performed using a general device or method. For example, a spray drying method, a drum drying method, a freeze-drying method, a vacuum (decompression) drying method, or the like can be used.

關於本發明之乳蛋白質水解物，以乳清蛋白水解物為例，通常用於此蛋白水解的酵素可為胃蛋白酶、胰蛋白酶及糜蛋白酶，也有研究報告使用植物源性的木瓜蛋白酶、細菌或菌類源性的蛋白酶(Food Technol.,48: 68-71,1994；Trends Food Sci. Technol.,7: 120-125,1996；Food Proteins and Their Applications,pp. 443-472,1997)。水解乳清蛋白的酵素活性變動大。胃蛋白酶可水解α-La及變性的α-La，但無法水解未變性的(native)β-Lg(Neth. Milk dairy J.,47: 15-22,1993)。胰蛋白酶可緩慢地水解α-La，但幾乎無法分解β-Lg(Neth. Milk dairy J.,45: 225-240,1991)。糜蛋白酶可快速地分解α-La，但僅可緩慢地分解β-Lg。木瓜蛋白酶可水解牛血清白蛋白(BSA)及β-Lg，但α-La有抗性(Int. Dairy Journal 6: 13-31,1996a)。因此，未與Ca結合的α-La在酸性環境中被木瓜蛋白酶完全分解(J. Dairy Sci.,76: 311-320,1993)。Regarding the milk protein hydrolysate of the present invention, taking whey protein hydrolysate as an example, the enzymes usually used for this protein hydrolysis may be pepsin, trypsin, and chymotrypsin. There are also reports of using plant-derived papain, bacteria, or Fungal-derived proteases (Food Technol., 48: 68-71, 1994; Trends Food Sci. Technol., 7: 120-125, 1996; Food Proteins and Their Applications, pp. 443-472, 1997). The enzyme activity of hydrolyzed whey protein varies greatly. Pepsin can hydrolyze α-La and denatured α-La, but cannot hydrolyze native β-Lg (Neth. Milk dairy J., 47: 15-22, 1993). Trypsin can slowly hydrolyze α-La, but can hardly break down β-Lg (Neth. Milk dairy J., 45: 225-240, 1991). Chymotrypsin can rapidly degrade α-La, but only slowly degrade β-Lg. Papain hydrolyzes bovine serum albumin (BSA) and β-Lg, but α-La is resistant (Int. Dairy Journal 6: 13-31, 1996a). Therefore, α-La not bound to Ca is completely decomposed by papain in an acidic environment (J. Dairy Sci., 76: 311-320, 1993).

藉由修飾蛋白質來控制乳蛋白的酵素分解，經由大範圍的pH及處理條件，可改變此蛋白的機能特性(Enzyme and Chemical Modification of proteins in Food proteins and their Applications,pp. 393-423,1997,Marcel Dekker,Inc.,New York,1997；Food Technol.,48: 68-71,1994)。By modifying the protein to control the enzymatic degradation of milk protein, the functional properties of this protein can be changed through a wide range of pH and processing conditions (Enzyme and Chemical Modification of proteins in Food proteins and their Applications, pp. 393-423, 1997, Marcel Dekker, Inc., New York, 1997; Food Technol., 48: 68-71, 1994).

胜肽鏈的水解會導致電荷數及疏水性的增加，低分子量化，以及分子立體結構的改變(J. Dairy Sci.,76: 311-320,1993)。功能特性的改變與水解度具有高度的相關性。與乳清蛋白的功能性相同，可見的最大的改變為溶解度增加及黏度下降。水解度高時，通常加熱水解物也不會產生沈澱，在pH 3.5～4.0時溶解性高。比起無處理(intact)的蛋白質，水解物的黏度大多較低。在蛋白質濃度高時，此差異特別顯著。其他的影響則包括膠特性的變化，熱安定性的增加，乳化及起泡性的增加、乳化及泡沫穩定性的下降(Int. Dairy journal,6: 13-31,1996a；Dairy Chemistry 4,pp. 347-376,1989；J. Dairy Sci.,79: 782-790,1996)。Hydrolysis of the peptide chain results in an increase in charge number and hydrophobicity, a decrease in molecular weight, and a change in the molecular stereostructure (J. Dairy Sci., 76: 311-320, 1993). The change of functional characteristics is highly correlated with the degree of hydrolysis. As functional as whey protein, the biggest changes seen are increased solubility and decreased viscosity. When the degree of hydrolysis is high, the hydrolysate usually does not precipitate when heated, and its solubility is high at pH 3.5 to 4.0. Most hydrolysates have lower viscosity than intact proteins. This difference is particularly significant at high protein concentrations. Other effects include changes in gum properties, increased thermal stability, increased emulsification and foaming properties, and decreased emulsification and foam stability (Int. Dairy journal, 6: 13-31, 1996a; Dairy Chemistry 4, pp. 347-376, 1989; J. Dairy Sci., 79: 782-790, 1996).

已知從乳蛋白產生的各種生理活性的寡胜肽(吉川正明「牛奶的高級功能」吉川正明等編，p 188-195，弘學出版，1998；大谷元「牛奶的高級功能」吉川正明等編，p 97-99，弘學出版，1998；大谷元、Milk Science 47: 183,1998；Trends in Food Science and Technology,9: 307-319,1998)。具抑制血管收縮素轉化酶(ACE)活性的胜肽(具降血壓作用)也屬於其中之一。Oligo-peptides of various physiological activities known from milk proteins (edited by Masaaki Yoshikawa, "Advanced Functions of Milk" edited by Masaaki Yoshikawa, etc., p 188-195, Hongxue Publishing, 1998; Masaaki Otani, "Advanced Functions of Milk" Yoshikawa Editor, p 97-99, Hongxue Publishing, 1998; Otani, Milk Science 47: 183, 1998; Trends in Food Science and Technology, 9: 307-319, 1998). Peptides with angiotensin-converting enzyme (ACE) inhibitory activity (with antihypertensive effect) are also among them.

由體外(in vitro)活性試驗推測的關於可能具有抑制ACE活性的多數個胜肽已有報導(例如，J. Dairy Res.,67: 53-64,2000；Br. J. Nutr.,84: S33-S37,2000)。已有許多文獻揭示使用各種層析技術由水解物精製及鑑定抑制ACE的胜肽。(例如，Maruyama,S.,& Suzuki,H.,Agricultural and Biological Chemistry,46: 1393-1394,1982；Miyoshi S. et al.,Agri. Biol. Chem.,55: 1313-1318,1991；Food Science and Biotechnology,8: 172-178,1999；Biosci. Biotech. Biochem.,57: 922-925,1993)。The majority of peptides that may have ACE-inhibitory activity have been reported from in vitro activity tests (e.g., J. Dairy Res., 67: 53-64, 2000; Br. J. Nutr., 84: S33-S37, 2000). Numerous literatures have revealed the use of various chromatography techniques to refine and identify peptides that inhibit ACE from hydrolysates. (E.g. Maruyama, S., & Suzuki, H., Agricultural and Biological Chemistry, 46: 1393-1394, 1982; Miyoshi S. et al., Agri. Biol. Chem., 55: 1313-1318, 1991; Food Science and Biotechnology, 8: 172-178, 1999; Biosci. Biotech. Biochem., 57: 922-925, 1993).

由這些文獻可知，ACE抑制活性存在於以各種分離原理的管柱操作所獲得的許多分液部份，這些顯示ACE抑制物質的分子特性有許多樣態。由各種蛋白質、蛋白酶及水解條件所產生的水解物中發現ACE抑制的事實，表示含有各種胺基酸序列的各種胜肽具有ACE抑制活性的可能性。由於上述胜肽具有化學多樣性，因此水解物經層析法的精製時常伴隨部分活性胜肽的損失。在水解過程中，ACE抑制活性連續形成，但另一方面不斷分解。水解物的最大活性為此述兩個步驟的最適化結果。水解物的整個胜肽組成決定ACE抑制活性，具有水解酵素的特異性及步驟條件依賴性。From these documents, it can be seen that ACE inhibitory activity exists in many liquid-separated fractions obtained by column operation with various separation principles, and these show many aspects of the molecular characteristics of ACE inhibitory substances. The fact that ACE inhibition is found in hydrolysates produced by various proteins, proteases, and hydrolysis conditions indicates the possibility that various peptides containing various amino acid sequences have ACE inhibitory activity. Due to the chemical diversity of the above peptides, purification of the hydrolysate by chromatography is often accompanied by a loss of some active peptides. During hydrolysis, ACE inhibitory activity is continuously formed, but on the other hand, it is continuously decomposed. The maximum activity of the hydrolysate is the result of the optimization of the two steps described. The entire peptide composition of the hydrolysate determines the ACE inhibitory activity, and has the specificity of the hydrolase and the step-condition dependence.

關於乳清蛋白水解的最佳化，已有文獻指出使用反應曲面法(response surface methodlogy)，以儘量減少所需要水解，來獲得最大化的ACE抑制活性(International Dairy Journal 12: 813-820,2002)。Regarding the optimization of whey protein hydrolysis, the literature has pointed out the use of response surface methodology to minimize the required hydrolysis to obtain the maximum ACE inhibitory activity (International Dairy Journal 12: 813-820, 2002 ).

本發明中所使用之乳蛋白質水解物，在體內(in vivo)可抑制由LPS誘導之TNF-α及IL-6的產生。在此，以LPS誘導之TNF-α及/或IL-6產生的抑制效果為指標，乳蛋白質的水解條件(變性溫度、pH、溫度、水解時間及酵素/基質比)的最適化，可參考上述文獻(International Dairy Journal 12: 813-820,2002)。The milk protein hydrolysate used in the present invention can inhibit the production of TNF-α and IL-6 induced by LPS in vivo. Here, taking the inhibitory effect of LPS-induced TNF-α and / or IL-6 as an indicator, the optimal conditions for the hydrolysis of milk proteins (denaturation temperature, pH, temperature, hydrolysis time, and enzyme / matrix ratio) can be referred to. The aforementioned literature (International Dairy Journal 12: 813-820, 2002).

另一方面，除了上述文獻外，也有許多專利(公開專利及專利)揭示乳蛋白質水解物的相關內容。例如，分別將酪蛋白及乳清蛋白水解，吸取/去除疏水性的部分後，以特定的比例混合兩者的專利(日本專利第2,986,764號)，以芽孢桿菌屬之蛋白酶及放線菌之蛋白酶水解乳清蛋白後，去除酵素及不溶性的水解物的專利(日本專利第3,222,638號)，以酵素分解β-乳球蛋白，獲得支鏈胺基酸/芳香族胺基酸的莫耳比在10重量%以上，芳香族胺基酸小於2.0重量%，平均分子量為數百～數千的胜肽混合物(日本專利第3,183,945號)，以酵素選擇性分解乳清蛋白中的β-乳球蛋白的專利(日本專利第2,794,305號)，或利用地衣芽孢桿菌(B. licheniformis)之蛋白酶及/或枯草芽孢桿菌(B. subtilis)之蛋白酶，以非-pH-stat法水解乳清蛋白至15～30%的水解度(DE)，獲得截留值(cut off)超過10,000之超濾膜的過濾液的專利(日本專利第3167723號)等。On the other hand, in addition to the above literatures, there are also many patents (published patents and patents) that disclose the content of milk protein hydrolysates. For example, a casein and a whey protein are hydrolyzed separately, and a hydrophobic portion is absorbed / removed, and then the two are mixed in a specific ratio (Japanese Patent No. 2,986,764) to hydrolyze by a protease of the genus Bacillus and a protease of an actinomycete Patent for removing enzymes and insoluble hydrolysates after whey protein (Japanese Patent No. 3,222,638), to decompose β-lactoglobulin by enzymes to obtain a branched chain amino acid / aromatic amino acid with a molar ratio of 10 weight % Or more, aromatic amino acid less than 2.0% by weight, peptide mixture with an average molecular weight of hundreds to thousands (Japanese Patent No. 3,183,945), a patent that selectively degrades β-lactoglobulin in whey protein by enzymes (Japanese Patent No. 2,794,305), or using a protease from B. licheniformis and / or a protease from B. subtilis to hydrolyze whey protein to 15-30% by non-pH-stat method Degree of hydrolysis (DE), a patent (Japanese Patent No. 3167723) for obtaining a filtrate of an ultrafiltration membrane with a cut off of more than 10,000.

上述文獻或專利的水解物是否具有抑制LPS誘導性TNF-α及IL-6產生的作用，可利用習知的分析系統(例如，實驗醫學別冊、「生物手冊UP實驗系列」、細胞激素實驗法、宮島篤、山本雅編、(株)羊土社、1997)進行分析。Whether the hydrolysates of the above-mentioned documents or patents have the effect of inhibiting the production of LPS-induced TNF-α and IL-6, can use a conventional analysis system (for example, a separate volume of experimental medicine, "biological handbook UP experiment series", cytokine experiment method , Atsushi Miyajima, Masahiro Yamamoto, Yangtusha Co., Ltd., 1997).

乳蛋白水解最佳化的5個參數，例如預熱、酵素/基質比(E/S)、pH、水解溫度、及水解的時間。5 parameters for milk protein hydrolysis optimization, such as preheating, enzyme / matrix ratio (E / S), pH, hydrolysis temperature, and hydrolysis time.

預熱：65～90℃Preheating: 65 ～ 90 ℃

E/S：0.01～0.2E / S: 0.01 ～ 0.2

pH：2～10pH: 2 ～ 10

水解溫度：30～65℃Hydrolysis temperature: 30 ～ 65 ℃

水解時間：3～不到20小時Hydrolysis time: 3 to less than 20 hours

使用的酵素，例如，擇自於下述諾和諾德公司的商品。The enzyme used is, for example, selected from the products of Novo Nordisk, which is described below.

1)內切型蛋白酶1) Endoprotease

地衣芽孢桿菌之蛋白酶：Alcalase(註冊商標)Protease from Bacillus licheniformis: Alcalase (registered trademark)

豆形桿菌(B. lentus)之蛋白酶：Esperase(註冊商標)Protease of B. lentus: Esperase (registered trademark)

枯草桿菌之蛋白酶：Neutrase(註冊商標)Protease from Bacillus subtilis: Neutrase (registered trademark)

細菌之蛋白酶：Protamex(註冊商標)Bacterial protease: Protamex (registered trademark)

豬胰蛋白酶：PTN(註冊商標)Porcine trypsin: PTN (registered trademark)

2)外切型蛋白酶2) Exoprotease

米麴菌(Aspergillus oryzae)之蛋白酶：Flavourzyme(登錄商標)Protease of Aspergillus oryzae: Flavourzyme (registered trademark)

豬或牛內臟之羧基胜肽酶Carboxypeptidase

除上述酵素外，也可為動物來源之胰酶、胃蛋白酶，植物來源之木瓜蛋白酶、菠蘿蛋白酶，微生物來源之(例如，乳酸菌、酵母菌、真菌、放線菌等)內切型蛋白酶及外切型蛋白酶，上述之純化物，菌體破碎物等。酵素組合物較佳為地衣芽孢桿菌之Alcalase與豬胰臟之PTN(胰蛋白酶)的組合。In addition to the above enzymes, trypsin and pepsin of animal origin, papain and bromelain of plant origin, and endogenous protease and exosome of microbial origin (for example, lactic acid bacteria, yeast, fungi, actinomycetes, etc.) Type protease, the above-mentioned purified product, bacterial cell disruption, etc. The enzyme composition is preferably a combination of Alcalase of Bacillus licheniformis and PTN (trypsin) of porcine pancreas.

乳清蛋白水解物的製造方法可參照後文比較例1中所記載的方法。As a method for producing a whey protein hydrolysate, a method described in Comparative Example 1 described later can be referred to.

本發明所使用的乳蛋白質水解物包含具有LPS誘導性TNF-α及/或IL-6產生的抑制效果的酵素水解物，經超過濾膜處理後的保持液、或過濾液(permeate)，以及具相同活性之市售乳蛋白質水解物。 The milk protein hydrolysate used in the present invention comprises an enzyme hydrolysate having an inhibitory effect on the production of LPS-induced TNF-α and / or IL-6, a holding solution or a permeate after being treated with an ultrafiltration membrane, and A commercially available milk protein hydrolysate with the same activity.

可使用於本發明之乳清蛋白水解物可為下列所述物質。專利第3183945號揭示，加熱變性的乳清蛋白分離物(WPI)以內切胜肽酶及外切胜肽酶水解後，以離子交換樹脂將此水解物中的芳香族胺基酸吸附處理，獲得Fisher比大於10，支鏈胺基酸15%以上，芳香族胺基酸小於2%之乳清蛋白水解物(分子量200~3,000之胜肽混合物)。 The whey protein hydrolysate which can be used in the present invention may be the substances described below. Patent No. 3183945 discloses that after thermally denatured whey protein isolate (WPI) is hydrolyzed with endo-peptidase and exo-peptidase, the aromatic amino acid in this hydrolysate is adsorbed and treated with an ion exchange resin to obtain Fisher's ratio greater than 10, branched amino acids above 15%, and aromatic amino acids below 2% of whey protein hydrolysate (molecular weight 200-3,000 peptide mixture).

特表平6-50756揭示蛋白質含量為至少65%乳清蛋白濃縮物(WPC)的12%水溶液，在超過60℃的熱處理後，以來自地衣芽孢桿菌(B.licheniformis)之Alcalase及來自枯草桿菌(B.subtilis)之中性蛋白酶(neutrase)水解至DH為15~35%，以截留值超過10,000的條件對此水解物進行超過濾(Ultrafiltration：UF)後，以奈過濾(Nanofiltration：NF)進行濃縮，將此NF濃縮液經噴霧乾燥後，獲得無臭，苦味少的乳清蛋白水解物。 Tiberium 6-50756 revealed that a 12% aqueous solution of a protein content of at least 65% whey protein concentrate (WPC), after heat treatment at more than 60 ° C, was obtained with Alcalase from B. licheniformis and from Bacillus subtilis (B.subtilis) neutral protease (neutrase) is hydrolyzed to 15 ~ 35% DH, and the hydrolysate is subjected to ultrafiltration (UF) with a cut-off value exceeding 10,000, and then subjected to nanofiltration (NF) After concentrating and spray-drying this NF concentrated solution, a whey protein hydrolysate having no odor and little bitterness was obtained.

本發明使用的乳蛋白質水解物可為一般市售產品，例如，Peptigen IF-3080、Peptigen IF-3090、Peptigen IF-3091及Lacprodan DI-3065(Arla Foods)、WE80BG(DMV)、Hyprol 3301、Hyprol 8361及Hyprol 8034(Kerry)、Tatua2016、HMP406(Tatua)、乳清蛋白水解7050(Fonterra)、Biozate3(Davisco)，但不限於此。蛋白質水解物的調整方法可例如包括下述1)~5)步驟之乳清蛋白水解物的製法。The milk protein hydrolysate used in the present invention may be a general commercial product, for example, Peptigen IF-3080, Peptigen IF-3090, Peptigen IF-3091, Lacprodan DI-3065 (Arla Foods), WE80BG (DMV), Hyprol 3301, Hyprol 8361 and Hyprol 8034 (Kerry), Tatua 2016, HMP406 (Tatua), Whey Protein Hydrolyzed 7050 (Fonterra), Biozate3 (Davisco), but not limited thereto. The method for adjusting a protein hydrolysate may include, for example, a method for producing a whey protein hydrolysate in the following steps 1) to 5).

1)將含有經計算至少65%蛋白質之乳清蛋白的乾燥物與水混合後，形成蛋白質含量為20%的泥狀物，1) Mixing a dried whey protein containing at least 65% of protein with water to form a mud with a protein content of 20%,

2)以超過60℃的溫度進行熱處理，2) heat treatment at a temperature exceeding 60 ° C,

3)將步驟2)之混合物經地衣芽孢桿菌(B. licheniformis)之蛋白酶，及/或以枯草桿菌(B. subtilis)之蛋白酶，以非-pH-stat法水解至15～35%之間的DH之蛋白分解性，3) The mixture of step 2) is hydrolyzed by a protease from B. licheniformis and / or a protease from B. subtilis to a concentration between 15 and 35% by a non-pH-stat method. Proteolytic properties of DH,

4)將步驟3之混合物，在截留值超過10,000之超過濾/微過濾裝置上，分離成過濾物由蛋白質水解產物所構成，以及4) separating the mixture of step 3 on an ultrafiltration / microfiltration device with a cut-off value exceeding 10,000, and separating the filtrate into a protein hydrolysate, and

5)此水解在上述酵素失活下結束。5) This hydrolysis ends when the enzyme is deactivated.

上述步驟1)中的泥狀物較佳含有7～12%的蛋白質含量。The mud in step 1) above preferably contains a protein content of 7-12%.

上述步驟2)中的熱處理較佳在約70至90℃之間進行。The heat treatment in the above step 2) is preferably performed at about 70 to 90 ° C.

上述步驟3)中的水解較佳進行至20～30%之間的DH。The hydrolysis in step 3) is preferably carried out to a DH between 20 and 30%.

上述超過濾/微過濾裝置的截留值較佳超過50,000。The cut-off value of the above-mentioned ultrafiltration / microfiltration device preferably exceeds 50,000.

上述步驟3)或步驟5)結束時的混合物，關於乾燥物含量被計算，為相對於碳的1至5%之間的量，較佳於50至70℃之間的溫度下，以活性碳處理較5分鐘長的時間，之後移除此活性碳。The mixture at the end of step 3) or step 5) above is calculated with respect to the dry matter content, which is an amount between 1 and 5% relative to carbon, preferably at a temperature between 50 and 70 ° C, with activated carbon. The treatment took longer than 5 minutes before removing this activated carbon.

上述步驟5)後的濃縮較佳於50至70℃之間的溫度，進行奈米級過濾/超過濾/逆滲透、及/或蒸發後，此剩餘物為蛋白質水解物溶液而被回收。The concentration after the step 5) is preferably at a temperature between 50 and 70 ° C. After performing nano-filtration / ultrafiltration / reverse osmosis and / or evaporation, the residue is recovered as a protein hydrolysate solution.

上述步驟5)所得的蛋白質水解產物溶液以噴霧乾燥至水含量低於6.5%。The protein hydrolysate solution obtained in step 5) is spray-dried to a water content of less than 6.5%.

因此，乳清蛋白水解物的製造方法為：Therefore, the manufacturing method of whey protein hydrolysate is:

1)將含有以乾燥物計算之至少65%蛋白質的乳清蛋白與水混合，形成蛋白質含量至約20%，較佳至12%的泥狀物，1) mixing whey protein containing at least 65% protein in dry matter with water to form a slime having a protein content of about 20%, preferably 12%,

3)將步驟2)之混合物利用地衣芽孢桿菌(B. licheniformis)之蛋白酶，較佳為Alcalase(註冊商標)，及/或以枯草桿菌(B. subtilis)之蛋白酶，較佳為Neutrase(註冊商標)，以非-pH-stat水解至15～35%的水解度(DE)，進行蛋白分解性水解，3) Use the protease of B. licheniformis, preferably Alcalase (registered trademark), and / or the protease of B. subtilis, preferably Neutrase (registered trademark), for the mixture in step 2). ), Non-pH-stat hydrolysis to 15 to 35% degree of hydrolysis (DE), proteolytic hydrolysis,

4)將步驟3之混合物，在截留值超過10,000之超過濾/微過濾裝置上進行分離，其過濾物構成上述蛋白質水解物，之後4) The mixture of step 3 is separated on an ultrafiltration / microfiltration device with a cut-off value exceeding 10,000, and the filtrate constitutes the protein hydrolysate described above.

5)此水解步驟在上述酵素失活下結束。5) This hydrolysis step ends with the enzyme inactivation described above.

乳清蛋白水解物(IF-3090)的胺基酸組成如表1所示。The amino acid composition of whey protein hydrolysate (IF-3090) is shown in Table 1.

相對於全部組成物，乳蛋白質水解物的調配量，例如0.1～22%，通常介於4.1～14.0%，較佳為5.5～10.0%的比例調配。每100 ml的組成物中，可調配0.9～3g，較佳為1.2～2g。The blending amount of the milk protein hydrolysate with respect to the entire composition is, for example, 0.1 to 22%, usually between 4.1 to 14.0%, and preferably 5.5 to 10.0%. For every 100 ml of the composition, 0.9 to 3 g, preferably 1.2 to 2 g, may be prepared.

本發明中所使用之源自醱酵乳之蛋白質的調配原料可為，例如，減少醱酵乳(優格)中水分(乳清)之物質(例如，日本特許第3,179,555號)。來自醱酵乳(優格)的蛋白質，其胺基酸級數(score)為100，經醱酵使蛋白質較容易消化吸收，具有較高的營養價值。The raw material for fermented milk-derived protein used in the present invention may be, for example, a substance that reduces moisture (whey) in fermented milk (yog) (for example, Japanese Patent No. 3,179,555). The protein from fermented milk (yog) has an amino acid score of 100. The fermented protein makes the protein easier to digest and absorb, and has higher nutritional value.

本發明中所使用之源自醱酵乳之蛋白質較佳為來自新鮮乳酪(非成熟乳酪(起司))之蛋白質。來自新鮮乳酪之蛋白質，蛋白質包含作為主成分之酪蛋白，含有α-乳蛋白或β-乳球蛋白之乳清蛋白，及部分乳蛋白分解為胺基酸或胜肽的成分。新鮮乳酪可為鄉村(Cottage)、夸克(Quark)、起司條(String)、納沙特爾(Neufchatel)、奶油起司(cream cheese)、莫薩里拉(mozzarella)、瑞可達(ricotta)、瑪斯卡波(Mascarpone)等多種種類，在本發明中，較佳使用夸克(Quark)。夸克(Quark)的製造方法為公眾所悉知(例如，特開平6-228013)。夸克(Quark)的脂肪含量較低，具有清爽風味及酸味。The protein derived from fermented milk used in the present invention is preferably a protein derived from fresh cheese (immature cheese (cheese)). Protein from fresh cheese. The protein contains casein as the main component, whey protein containing α-lactoprotein or β-lactoglobulin, and a part of milk protein that is broken down into amino acids or peptides. Fresh cheese can be Cottage, Quark, String, Neufchatel, Cream Cheese, Mozzarella, Ricotta, There are various types such as Mascarpone. In the present invention, Quark is preferably used. The manufacturing method of Quark is known to the public (for example, Japanese Patent Application Laid-Open No. 6-228013). Quark has a low fat content and has a refreshing flavor and sour taste.

非熟成乳酪的一般製造方法如下說明。首先，由乳原料製成凝乳。於乳原料中接種起始物後進行培養，再加入凝乳酶以形成凝乳(curd)。在製造凝乳之前，可視需要對原料乳進行前處理。例如，為縮小各製造批次間的品質差異，可混合多種的乳原料以控制品質。這種處理又稱為標準化。更可以增加以機械破壤乳中脂肪球的均質化(homogenize)處理。或者也可以離心滅菌或加熱處理去除乳原料中的微生物。A general method for producing non-aged cheese is described below. First, curd is made from milk ingredients. After inoculating the starting material in the milk raw material, it is cultured, and then rennetase is added to form curd. Before manufacturing the curd, the raw milk may be pretreated as necessary. For example, in order to reduce the quality difference between manufacturing batches, multiple types of milk raw materials can be mixed to control the quality. This process is also called standardization. It is also possible to increase the homogenization of fat globules in mechanically broken milk. Alternatively, microorganisms may be removed from the milk material by centrifugal sterilization or heat treatment.

由所獲得之凝乳(curd)分離出乳清(whey)，所獲得之固形物為非熟成乳酪(新鮮乳酪)。利用離心分離或膜分離將乳清由凝乳中分離出來的方法為一般所悉知。例如，可利用夸克(Quark)分離器等離心機來分離乳清。如有必要的話，可事先切割凝乳或加熱，以增加分離程序的效率。Whey was separated from the obtained curd, and the solid obtained was unripe cheese (fresh cheese). A method for separating whey from curd by centrifugation or membrane separation is generally known. For example, a centrifuge such as a Quark separator may be used to separate whey. If necessary, the curd can be cut or heated in advance to increase the efficiency of the separation process.

更具體地，以下述原料及步驟所獲得的新鮮乳酪較佳為本發明之醱酵乳成分。在以下步驟中，醱酵主要使用保加利亞乳酸桿菌(Lactobacillus bulgaricus)及/或嗜熱鏈球菌(Streptococcus thermophilus)。More specifically, the fresh cheese obtained by the following raw materials and steps is preferably the fermented milk ingredient of the present invention. In the following steps, Lactobacillus bulgaricus and / or Streptococcus thermophilus are mainly used for the fermentation.

將脫脂牛乳加熱殺菌；接種0.5～5%的乳酸菌起始物，開始醱酵；在pH到達4.6時，所形成之凝乳(curd)中分離乳清；將分離乳清之凝乳冷卻，獲得非熟成乳酪。Heat sterilized skim milk; inoculate 0.5 to 5% lactic acid bacteria starting material and start fermentation; when the pH reaches 4.6, separate whey from the curd formed; cool the whey separated curd to obtain Non-aged cheese.

由此方法所製造之非熟成乳酪，一般稱作為夸克(Quark)。非熟成乳酪的組成一例如下所示。The non-aged cheese made by this method is generally called Quark. An example of the composition of non-aged cheese is shown below.

總固形物17～19%，蛋白質11～13%，脂肪1%以上，碳水化合物2～8%，乳糖2%以上。Total solids are 17 to 19%, protein is 11 to 13%, fat is more than 1%, carbohydrates are 2 to 8%, and lactose is more than 2%.

相對於全部組成物，源自醱酵乳之蛋白質的調配量為，可例如0.1～30%，通常為8.0～23.0%，較佳為10.0～18.0%的比例調配。每100 ml的組成物中，調配2～6g，較佳為2.5～4.5g。相對於組成物整體的蛋白質量，本發明組成物整體所含的源自醱酵乳之蛋白質，可為約0.1～約90%，較佳為約1～約80%，更佳為約30～約70%。The amount of the protein derived from fermented milk relative to the entire composition may be, for example, 0.1 to 30%, usually 8.0 to 23.0%, and preferably 10.0 to 18.0%. For each 100 ml of the composition, 2 to 6 g, preferably 2.5 to 4.5 g, is prepared. Relative to the overall protein quality of the composition, the protein derived from fermented milk contained in the composition of the present invention may be about 0.1 to about 90%, preferably about 1 to about 80%, and more preferably about 30 to about 70%.

本發明之組成物含有作為脂質的油脂。The composition of the present invention contains fats and oils as lipids.

本發明之組成物較佳含有n-3系脂肪酸。本發明組成物中所含之n-3系脂肪酸可為EPA、DHA、α-亞麻酸、DPA等，較佳為EPA、DHA、或/及α-亞麻酸，更佳為EPA或/及DHA。含n-3系脂肪酸之油脂包括紫蘇油、亞麻油、胡麻油、魚油、菜籽油、大豆油、沙拉油、亞麻仁油等。在本發明中可直接含有這些n-3系脂肪酸，也可以魚油等油脂的形式含有。The composition of the present invention preferably contains an n-3 fatty acid. The n-3 fatty acids contained in the composition of the present invention may be EPA, DHA, α-linolenic acid, DPA, etc., preferably EPA, DHA, or / and α-linolenic acid, and more preferably EPA or / and DHA . Oils containing n-3 fatty acids include perilla oil, linseed oil, flax oil, fish oil, rapeseed oil, soybean oil, salad oil, linseed oil, and the like. These n-3 fatty acids may be contained directly in the present invention, or may be contained in the form of oils and fats such as fish oil.

本發明之組成物較佳含有中鏈三酸甘油酯(MCT:medium-chain triglyceride)作為脂質。MCT在體內被可快速地被吸收而形成能量，具有不易於體內形成脂肪的特徵。含有MCT之油脂包括棕櫚油、棕櫚仁油、含中鏈脂肪酸之油脂等。在本發明中，可直接含有MCT，也可以棕櫚仁油等油脂的形式含有。The composition of the present invention preferably contains a medium-chain triglyceride (MCT) as a lipid. MCT is quickly absorbed into the body to form energy, and has the feature that it is not easy to form fat in the body. MCT-containing fats include palm oil, palm kernel oil, fats containing medium-chain fatty acids, and the like. In the present invention, MCT may be contained directly, or may be contained in the form of oils and fats such as palm kernel oil.

因此，本發明之組成物包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之中鏈三酸甘油酯、EPA、及/或DHA，以及作為糖類之異麥芽酮糖。Therefore, the composition of the present invention includes a milk protein hydrolysate as a protein and a protein derived from fermented milk, a medium-chain triglyceride, EPA, and / or DHA as a lipid, and isomaltulose as a sugar.

另一方面，本發明之組成物可含有油酸、棕櫚酸、棕櫚油酸、亞麻油酸、硬脂酸、次亞麻油酸、花生四烯酸等脂肪酸，較佳以油酸作為脂質。含有這些脂肪酸之油脂包括，例如高油酸之高油酸葵花籽油、菜籽油、橄欖油、高油酸紅花油、大豆油、玉米油、棕櫚油等。可也使用葵花籽油、菜籽油、橄欖油、及橄欖油混合物。亞麻油酸、花生四烯酸、γ-次亞麻油酸等為n-6系脂肪酸。含n-6系脂肪酸之油脂包括紅花油、葵花籽油、大豆油、亞麻油、玉米油、花生油等。On the other hand, the composition of the present invention may contain fatty acids such as oleic acid, palmitic acid, palmitoleic acid, linoleic acid, stearic acid, hypolinolenic acid, and arachidonic acid, and oleic acid is preferably used as the lipid. Fats and oils containing these fatty acids include, for example, high oleic high oleic sunflower oil, rapeseed oil, olive oil, high oleic safflower oil, soybean oil, corn oil, palm oil, and the like. Sunflower oil, rapeseed oil, olive oil, and olive oil mixtures can also be used. Linoleic acid, arachidonic acid, γ-linolenic acid and the like are n-6 fatty acids. Oils containing n-6 fatty acids include safflower oil, sunflower oil, soybean oil, linseed oil, corn oil, peanut oil, etc.

n-3系脂肪酸與n-6系脂肪酸的比例，對於n-3系脂肪酸為1時，n-6系脂肪酸為例如5以下，通常為0.5以上4.0以下，較佳為1.0以上4.0以下，更佳為n-3系脂肪酸：n-6系脂肪酸=1：2的比例。The ratio of n-3 fatty acids to n-6 fatty acids is 1. For n-3 fatty acids, the n-6 fatty acids are, for example, 5 or less, usually 0.5 or more and 4.0 or less, preferably 1.0 or more and 4.0 or less, and more The ratio of n-3 fatty acids: n-6 fatty acids = 1: 2 is preferred.

相對於全部組成物，n-3系脂肪酸的調配量，以例如0.01～10%，通常為0.05～7%，較佳為0.1～5%之比例調配。每100 ml的組成物，可調配0.05～2.2g，較佳為0.1～1.0g。The compounding amount of the n-3 fatty acid with respect to the entire composition is, for example, 0.01 to 10%, usually 0.05 to 7%, and preferably 0.1 to 5%. For each 100 ml of the composition, 0.05-2.2 g, preferably 0.1-1.0 g, can be prepared.

相對於全部組成物，MCT的調配量，以例如0.01～14.5%，通常為0.01～8.0%，較佳為2.0～4.0%的比例調配。每100 ml的組成物，可調配0.01～2.0g，較佳為0.5～1.0g。The compounding amount of MCT is formulated at a ratio of, for example, 0.01 to 14.5%, usually 0.01 to 8.0%, and preferably 2.0 to 4.0% with respect to the entire composition. For each 100 ml of the composition, 0.01 to 2.0 g, preferably 0.5 to 1.0 g, can be prepared.

相對於全部組成物，含有油酸的油脂調配量，以例如0.1～14.5%，通常為2.0～10.0%，較佳為4.0～8.0%的比例調配。每100 ml的組成物，可調配0.5～2.0g，較佳為1.0～1.8g。The blending amount of oleic acid-containing oil and fat with respect to the entire composition is blended at a ratio of, for example, 0.1 to 14.5%, usually 2.0 to 10.0%, and preferably 4.0 to 8.0%. For each 100 ml of the composition, 0.5 to 2.0 g, preferably 1.0 to 1.8 g, can be prepared.

本發明之組成物也可含有作為脂質的牛奶卵磷質或大豆卵磷質。The composition of the present invention may also contain milk lecithin or soybean lecithin as lipids.

牛奶卵磷質及大豆卵磷質可個別單獨含有，也可組合。Milk egg phosphorus and soybean egg phosphorus can be contained individually or in combination.

牛奶卵磷質可由鞘磷脂(SM)、磷脂醯膽鹼(PC)、磷脂醯乙醇胺(PE)、磷脂醯肌醇(PI)、磷脂醯絲胺酸(PS)、溶血磷脂醯膽鹼(LPC)所形成，且僅局部存在於乳脂肪球膜(MFGM)中。MFGM磷脂質級分的成分組成如表2(乳業技術Bulletin of Japan Dairy Technical Association,Vol. 50：pp. 58-91,2000)所示。Milk lecithin can be sphingomyelin (SM), phospholipids choline (PC), phospholipids ethanolamine (PE), phospholipids inositol (PI), phospholipids serine (PS), lysophospholipids choline (LPC ) And is only partially present in milk fat globule membrane (MFGM). The composition of the MFGM phospholipid fraction is shown in Table 2 (Bulletin of Japan Dairy Technical Association, Vol. 50: pp. 58-91, 2000).

雖然“卵磷脂”一詞在生物化學、醫學、藥學等領域中僅用於表示磷脂醯膽鹼，但在商業或工業上，為磷脂醯膽鹼、磷脂醯乙醇胺、磷脂醯肌醇、磷脂酸及其他磷脂質混合物的總稱。於食品添加物公定書第7版(1999)中，卵磷脂的定義為「由糧油種子或動物原料所獲得之物質，其主成分為磷脂質」。本發明中來自乳的磷脂質也可統稱為「牛奶卵磷脂」。Although the term "lecithin" is only used in the fields of biochemistry, medicine, pharmacy, etc. to indicate phospholipids, choline, but in the commercial or industrial fields, they are phospholipids, choline, phospholipids, ethanolamine, phospholipids, inositol, and phosphatidic acid And other phospholipid mixtures. In the 7th edition (1999) of the Food Additives Public Draft, lecithin is defined as "a substance obtained from grain and oil seeds or animal raw materials, the main component of which is phospholipid". The phospholipids derived from milk in the present invention may also be collectively referred to as "milk lecithin".

牛奶卵磷脂的特徵如表2所示，不含有大豆卵磷脂，但含有大量的SM。目前已知，與大豆卵磷脂相比，在將牛奶卵磷脂投予大鼠時，腦及肝臟內的DHA含量增加，且與大豆卵磷脂或蛋黃卵磷脂相比，有效地改善高脂血症或脂肪肝。又SM已知調控與膽固醇生合成有關之HMG-CoA還原酶的活性，與腸道中膽固醇的吸收有關等，已知SM與膽固醇的代謝有關。由上述推測，SM可使PC或PE的脂質代謝效果更為提升(佐佐木一，Milk Science 51(2): 93-94,2002)。The characteristics of milk lecithin are shown in Table 2. It does not contain soy lecithin, but contains a large amount of SM. It is currently known that when milk lecithin is administered to rats compared to soybean lecithin, DHA content in the brain and liver is increased, and compared with soybean lecithin or egg yolk lecithin, it effectively improves hyperlipidemia Or fatty liver. SM is also known to regulate the activity of HMG-CoA reductase, which is related to cholesterol biosynthesis, and is related to the absorption of cholesterol in the intestine. SM is known to be related to cholesterol metabolism. From the above speculation, SM can further enhance the lipid metabolism effect of PC or PE (Sasaki I, Milk Science 51 (2): 93-94, 2002).

含有大量MFGM的物質例如，合併超過濾(ultrafiltration：UF)及微過濾(microfiltration：MF)所製造之WPI副產物(MF保持液)的凍結乾燥物、去除奶油(Butter或Cream)的無水乳脂肪(anhydrous milk fat：AMF)後所獲得的級分(奶油乳清(Butter Serum))、去除乳清乳脂(whey cream)中AMF後所獲得的級分(whey cream serum)等。以這些作為原料獲得磷脂質濃縮物的方法為公眾所悉知(例如，包含於本發明的特開平7-173182)。Substances containing a large amount of MFGM, for example, freeze-dried products of WPI by-products (MF holding solution) produced by combining ultrafiltration (UF) and microfiltration (MF), and anhydrous milk fat from butter (Butter or Cream) (anhydrous milk fat: AMF), a fraction (Butter Serum), and a whey cream (whey cream serum) obtained by removing AMF from whey cream. A method for obtaining a phospholipid concentrate using these as raw materials is known to the public (for example, it is contained in Japanese Patent Application Laid-Open No. 7-173182).

大豆卵磷脂為天然的食品添加物，一方面廣泛地使用於食品領域，多烯磷脂膽鹼(polyenephosphatidylcholine)也可作為醫藥品(適應症：改善慢性肝病患者的肝臟功能、脂肪肝、高血脂症)。大豆卵磷脂的生理作用例如：(1)生體膜的形態與機能的調控、(2)肺功能的改善、(3)動脈硬化症的改善、(4)脂質代謝的改善、(5)肝臟脂質代謝的改善，以及(6)神經功能的改善/提升(食品與開發，Vol. 29(3)：18-21,1994)。Soy lecithin is a natural food additive. On the one hand, it is widely used in the food field. Polyenephosphatidylcholine can also be used as a medicine (Indications: Improve liver function in patients with chronic liver disease, fatty liver, hyperlipidemia ). The physiological effects of soy lecithin are, for example: (1) regulation of morphology and function of biofilm, (2) improvement of lung function, (3) improvement of arteriosclerosis, (4) improvement of lipid metabolism, (5) liver Improvement of lipid metabolism and (6) improvement / promotion of neural function (Food and Development, Vol. 29 (3): 18-21, 1994).

關於所謂的「天然」的一系列卵磷脂製品，基本上是依製品中的PC含量排列。依照卵磷脂的用途，製造提高等級的各種卵磷脂。根據經過大豆卵磷脂的精製、級分使而主要的PC含量不同，大豆卵磷脂製品簡單地分類如表3所示(藤川琢馬、油化學第40卷(10),pp. 951-p58,1991)。A series of so-called "natural" lecithin products are basically arranged according to the PC content in the products. According to the application of lecithin, various kinds of lecithin are produced. Soy lecithin products are simply classified as shown in Table 3 according to the main PC content after soy lecithin purification and fractionation (Fujikawa Takuma, Petrochemicals Vol. 40 (10), pp. 951-p58, 1991).

本發明之組成物含有作為糖類之異麥芽酮糖(palatinose(註冊商標))。異麥芽酮糖的CAS登錄號為13718-94-0，化學式為C₁₂H₂₂O₁₁。The composition of the present invention contains isomaltulose (palatinose (registered trademark)) as a sugar. Isomaltulose has a CAS registration number of 13718-94-0 and a chemical formula of C ₁₂ H ₂₂ O ₁₁ .

異麥芽酮糖包括還元之異麥芽酮糖、Palatinose糖漿(登錄商標)、或異麥芽酮糖糖漿等。異麥芽酮糖糖漿為將異麥芽酮糖進行脫水縮合所產生的由四糖、六糖、八糖等寡糖為主成分之糖漿狀液狀物。異麥芽酮糖與蔗糖相同，被分解為葡萄糖與果糖而被吸收(合田敏尚等、日本營養‧食糧學會誌，Vol. 36(3): 169-173,1983)，但是由於其水解速度較慢，為蔗糖的1/5(Tsuji,Y. et al.,J. Nutr. Sci. Vitaminol.,32: 93-100,1986)，攝取後，血中葡萄糖與胰島素的濃度長時間維持在一定的程度(Kawai,K. et al.,Endocrinol,Japan,32(6): 933-936,1985)。Isomaltulose includes reduced isomaltulose, Palatinose syrup (registered trademark), isomaltulose syrup, and the like. Isomaltulose syrup is a syrupy liquid substance mainly composed of oligosaccharides such as tetrasaccharide, hexasaccharide, and octose, which is produced by dehydration and condensation of isomaltulose. Isomaltulose is the same as sucrose, and is decomposed into glucose and fructose and absorbed (Hita Minsho et al., Journal of the Japan Institute of Nutrition and Food Science, Vol. 36 (3): 169-173, 1983), but its hydrolysis rate is relatively slow. Slow, 1/5 of sucrose (Tsuji, Y. et al., J. Nutr. Sci. Vitaminol., 32: 93-100, 1986). After ingestion, the blood glucose and insulin concentrations remain constant for a long time. (Kawai, K. et al., Endocrinol, Japan, 32 (6): 933-936, 1985).

相對於全部組成物，異麥芽酮糖的調配量，以例如10～70%，通常為15～60%，較佳為20～35%的比例調配。每100 ml的組成物可調配4～13g，較佳為5～8g。The blending amount of isomaltulose relative to the entire composition is, for example, 10 to 70%, usually 15 to 60%, and preferably 20 to 35%. For each 100 ml of the composition, 4 to 13 g, preferably 5 to 8 g, can be prepared.

本發明組成物為促進小腸絨毛的生長，增加小腸肌肉層的厚度，改善腸道功能，預防小腸組織損害，或抑制各種的炎症，以投予對象為一目的而使用。The composition of the invention is used for the purpose of promoting the growth of small intestine villi, increasing the thickness of the small intestine muscle layer, improving intestinal function, preventing damage to small intestine tissue, or inhibiting various inflammations.

本發明中所述之「對象」並無特別限定，包含動物(例如，人類、家畜動物、野生動物)。「對象」不必為罹患疾病之患者，例如，本發明之組成物也可以健康的人類作為投予對象。The "target" described in the present invention is not particularly limited and includes animals (for example, humans, livestock animals, and wild animals). The "subject" does not need to be a patient suffering from a disease. For example, the composition of the present invention can also be administered to a healthy human.

本發明中所述之「投予」包括經口、或非經口的投予，其投予型態可為醫藥品或飲食。The "administration" described in the present invention includes oral or non-oral administration, and the administration form may be a medicine or a diet.

本發明之組成物可以醫藥組成物、營養醫藥組成物、醫藥品、藥劑、飲食組成物、飲食品、營養組成物、特別用途食品、營養機能食品、健康食品、醫藥品添加物、食品添加物等任一形式來利用。例如，本發明之組成物可作為為了營養均衡之健康人所用的小腸功能改善食品、營養不良之高齡者的營養改善食品、呼吸、循環、代謝等重度機能不全患者(ICU患者)的腸道功能維持食品、具有腦‧神經損害的吞嚥困難患者的營養補給與腸道功能維持食品、潰瘍性大腸炎或克隆氏病等慢性腸疾病用用的腸道功能改善與營養狀態改善食品、對慢性閉塞性肺疾患(COPD)營養不良之腸道功能改善與營養狀態改善食品，或對癌症患者等因抗生素或抗癌藥物等所致腸道損害患者的腸道功能改善與營養狀態改善的食品而利用。The composition of the present invention can be a pharmaceutical composition, a nutritional pharmaceutical composition, a medicine, a medicament, a dietary composition, a dietary product, a nutritional composition, a special purpose food, a nutritional functional food, a health food, a pharmaceutical additive, and a food additive Wait for any form to use. For example, the composition of the present invention can be used as a small intestine function-improving food for nutritionally balanced healthy people, a nutrition-improving food for elderly people who are malnourished, and intestinal functions of patients with severe insufficiency such as respiration, circulation, and metabolism (ICU patients). Maintenance of food, nutritional supplementation and intestinal function for patients with dysphagia with brain and nerve damage Maintenance of food, improvement of intestinal function and nutritional status for chronic intestinal diseases such as ulcerative colitis or Crohn's disease Foods with improved intestinal function and nutritional status in patients with chronic lung disease (COPD) malnutrition, or foods with improved intestinal function and nutritional status in patients with intestinal damage caused by antibiotics or anticancer drugs, such as cancer patients .

本發明之醫藥組成物、營養醫藥組成物、醫藥品、藥劑可含於飲食組成物、飲食品、營養組成物、特別用途食品、營養機能食品、健康食品等中。例如，本發明之醫藥組成物、營養醫藥組成物、醫藥品、藥劑也可含於為了營養均衡之健康人所用的小腸功能改善食品、營養不良之高齡者的營養改善食品、呼吸、循環、代謝等重度機能不全患者(ICU患者)的腸道功能維持食品、具有腦‧神經損害的吞嚥困難患者的營養補給與腸道功能維持食品、潰瘍性大腸炎或克隆氏病等慢性腸疾病用用的腸道功能改善與營養狀態改善食品、對慢性閉塞性肺疾患(COPD)營養不良之腸道功能改善與營養狀態改善食品，或對癌症患者等因抗生素或抗癌藥物等所致腸道損害患者的腸道功能改善與營養狀態改善的食品中而利用。The medicinal composition, nutritional medicinal composition, medicine and medicament of the present invention may be contained in dietary composition, dietary food, nutritional composition, special purpose food, nutritional functional food, health food and the like. For example, the medicinal composition, nutritional medicinal composition, medicine, and medicament of the present invention may also be included in small intestinal function-improving foods used for healthy people with balanced nutrition, and nutrition-improving foods for elderly people with malnutrition, breathing, circulation, and metabolism. Food for maintaining intestinal function in patients with equal severe insufficiency (ICU patients), nutritional supply for patients with dysphagia with brain and nerve damage, and food for maintaining intestinal function, chronic intestinal diseases such as ulcerative colitis or Crohn's disease Foods with improved intestinal function and nutritional status, foods with improved intestinal function and nutritional status for chronic obstructive pulmonary disease (COPD) malnutrition, or patients with bowel damage caused by antibiotics or anticancer drugs, such as cancer patients It is used in foods with improved intestinal function and improved nutritional status.

例如，以醫藥品直接投予，或以特定保健用食品等特別用途食品或營養機能食品直接攝取，可預期促進對象的小腸絨毛生長、增加小腸肌肉層的厚度、改善腸道功能、預防小腸組織損害、或抑制各種炎症。For example, direct administration of pharmaceuticals or ingestion of special purpose foods such as specific health foods or nutritional functional foods can promote the growth of the small intestine villi, increase the thickness of the small intestinal muscle layer, improve intestinal function, and prevent small intestine tissue. Damage or inhibit various inflammations.

本發明之組成物在作為醫藥品使用時，可以各種形態投予。此形態可為，例如經腸營養劑、液劑等，經鼻管、胃瘻、腸瘻等經腸或經口投予，也可以加工成錠劑、膠囊、顆粒劑、散劑、糖漿等製劑的投予型態。上述各種製劑可依照一般習知的方法，使用賦形劑、結合劑、崩壞劑、潤滑劑、矯味劑、增溶劑、懸濁劑、塗層、溶劑、等強劑等的醫藥製劑技術領域中通常可使用的習知輔助劑與主劑製劑化。也可含有適量的鈣。也可額外添加適量的維生素、礦物質、有機酸、糖類、胺基酸、胜肽類等。When the composition of the present invention is used as a pharmaceutical, it can be administered in various forms. This form can be, for example, enteral nutrition, liquids, enteral or oral administration through nasal canals, gastrostoma, intestinal fistula, etc., or it can be processed into preparations such as tablets, capsules, granules, powders, syrups The type of administration. The above-mentioned various preparations can be used in accordance with generally known methods, and use of excipients, binding agents, disintegrating agents, lubricants, flavoring agents, solubilizers, suspending agents, coatings, solvents, and other strong pharmaceutical agents. Technical field Conventional adjuvants commonly used in the formulation of the main agent. May also contain appropriate amounts of calcium. You can also add appropriate amounts of vitamins, minerals, organic acids, sugars, amino acids, peptides, etc.

本發明之組成物在以醫藥品的形態使用時，可以經口或經腸投予。例如，可選擇經口投予之錠劑、膠囊、顆粒、散劑、糖漿等，或經腸投予之鼻管、胃瘻、腸瘻等，應依據患者的年齡、症狀選擇適合投予方式。有效投予量為每1kg體重每次投予0.1mg至1500mg的範圍。或可選擇對每位患者的投予量為5mg～75g，較佳為100mg～50g的投予量。較佳的投予量與投予方法，具體例，每1kg體重每次投予0.1mg至1500mg，較佳2mg至1000mg，每日投予1～3次，持續1個月(4週)，於飯前或飯後的方法。投予次數可藉由觀察投予後的狀態及血液檢查值的動向，並根據狀態來調整投予次數。When the composition of the present invention is used in the form of a pharmaceutical, it can be administered orally or enterally. For example, you can choose tablets, capsules, granules, powders, syrups, etc. to be administered orally, or nasal canals, gastrostomas, intestinal fistulas, etc., which should be administered according to the patient's age and symptoms. The effective dosage is in the range of 0.1 mg to 1500 mg per 1 kg of body weight. Alternatively, the dosage of 5 mg to 75 g, preferably 100 mg to 50 g, can be selected for each patient. The preferred dosage and method of administration, specific examples: 0.1 mg to 1500 mg, preferably 2 mg to 1000 mg per 1 kg of body weight, 1 to 3 times daily for 1 month (4 weeks), Before or after meals. The number of administrations can be observed by observing the state of the administration and the movement of the blood test value, and adjusting the number of administrations according to the state.

本發明之組成物在作為食品使用時，可以液狀、膏狀、固形、粉末等形態，添加至各種食品中，作為食品來進行攝取。飲品可例如牛奶、冷飲、醱酵乳、優格、乳酪、麵包、餅乾(biscuit)、餅乾(cracker)、披薩、調製奶粉、流質食品、病患用食品、營養食品、冷凍食品、食品組成物、加工食品等其他市售食品等。本發明之組成物在作為食品使用時，較佳為可直接使用的形態。以這種形態，組成物可經管通過鼻-胃、空腸、或經口攝取。此種組成物可為各種形態，例如果汁型飲料、奶昔型飲料等。組成物也可為使用前再形成的可溶性粉末。When the composition of the present invention is used as food, it can be added to various foods in the form of liquid, paste, solid, powder, etc., and ingested as food. Beverages can be, for example, milk, cold drinks, fermented milk, yogurt, cheese, bread, biscuit, cracker, pizza, prepared milk powder, liquid food, food for patients, nutritious food, frozen food, food composition, Processed foods and other commercially available foods. When the composition of the present invention is used as a food, it is preferably in a form that can be used directly. In this form, the composition can be ingested through the tube through the nose-stomach, jejunum, or orally. Such a composition can take various forms, for example, a fruit juice type drink, a milk shake type drink, etc. The composition may be a soluble powder formed before use.

組成物的滲透壓為約300～1000 mOsm/l，例如可為約300～750 mOsm/l。於室溫檢測時，組成物的黏度為約5～40 cp(1 cp=0.001 Pa‧s)，較佳小於20。The osmotic pressure of the composition is about 300 to 1000 mOsm / l, for example, about 300 to 750 mOsm / l. When measured at room temperature, the viscosity of the composition is about 5 to 40 cp (1 cp = 0.001 Pa · s), preferably less than 20.

組成物的卡路里為約1～2 kcal/ml，較佳為1～1.5 kcal/ml。The calorie of the composition is about 1 to 2 kcal / ml, and preferably 1 to 1.5 kcal / ml.

本發明之組成物在作為食品使用時，更可調配額外的營養素，以調整其營養組成。本發明中額外添加之營養素可為水、蛋白質、糖類、脂質、胺基酸、膳食纖維、維生素、礦物質、有機酸、有機鹼、果汁、調味類、人工甜味劑(例如，阿斯巴甜等)等。When the composition of the present invention is used as a food, additional nutrients can be adjusted to adjust its nutritional composition. The additional nutrients in the present invention may be water, protein, sugars, lipids, amino acids, dietary fiber, vitamins, minerals, organic acids, organic bases, fruit juices, flavors, artificial sweeteners (e.g., aspartame Sweet etc) etc.

可含有5 mg～500 mg(0.005%～0.5%)具降低糞便味道的香菇萃取物(champignon extract)、10μg～200μg(0.00001%～0.0002%)用於加強營養目的的類胡蘿蔔素製劑(例如，含有α-胡蘿蔔素、β-胡蘿蔔素、茄紅素、葉黃素等)。May contain 5 mg to 500 mg (0.005% to 0.5%) of champignon extract with reduced stool taste, 10 μg to 200 μg (0.00001% to 0.0002%) of a carotenoid preparation for nutritional purposes (for example, Contains α-carotene, β-carotene, lycopene, lutein, etc.).

再者，也可含有作為抗氧化劑之兒茶素、多酚等。Furthermore, catechin, polyphenols, etc. may be contained as an antioxidant.

而且，為了脂質代謝抗進等目的，可含有肉鹼(carnitine)。肉鹼為由離胺酸與甲硫胺酸在肝臟或腎臟中所形成之生物體微量成分。目前已知，肉鹼的生成量會隨著年齡增加而降低。L-肉鹼可攜帶長鏈脂肪酸進入肌肉細胞等，對營養成分的代謝非常重要。Carnitine may be contained for purposes such as lipid metabolism resistance. Carnitine is a trace component of the organism formed by lysine and methionine in the liver or kidneys. It is currently known that the amount of carnitine produced decreases with age. L-carnitine can carry long-chain fatty acids into muscle cells, etc., and is very important for the metabolism of nutrients.

糖類除了上述異麥芽酮糖之外，也可為其他多種糖類。異麥芽酮糖以外的糖質，使用蔗糖、葡萄糖、果糖、蜂蜜等。其他例如糊精、難分解性糊精。In addition to the isomaltulose mentioned above, the saccharides may also be various other saccharides. For sugars other than isomaltulose, sucrose, glucose, fructose, honey, and the like are used. Others include dextrin and refractory dextrin.

膳食纖維分成水溶性膳食纖維與不溶性膳食纖維，任一種皆可使用。Dietary fiber is divided into water-soluble dietary fiber and insoluble dietary fiber, and either one can be used.

水溶性膳食纖維可使用難分解性寡糖之乳果糖、乳糖醇、或棉子糖。目前已知，難分解性寡糖的生理功能為在未消化物到達大腸後，腸內比菲德氏菌活化及增生，改善腸內環境，亦即具有整腸效果。乳果糖為由半乳糖與果糖所形成之合成雙糖類，其為高血氨症的基本用藥(Bircher,J. et al.,Lancet i: 890,1965)。慢性肝功能衰竭之復發性慢性肝腦症對於投予乳果糖、用於肝功能不全之特殊胺基酸點滴(Fischer液)等，具有良好的反應。第二代之乳果糖“乳糖醇”(β-galactosyl-sorbitol)對於慢性肝腦症的臨床效果與乳果糖相同(Lanthier,PL. and Morgan,M.,Gut,26: 415,1985;Uribe,M.,et al.,Dig. Dis. Sci.,32: 1345,1987;Heredia,D. et al.,J. Hepatol,7: 106,1988;Riggio,0.,et al.,Dig. Dis. Sci.,34: 823,1989)，現在已作為高血氨症的治療用藥。As the water-soluble dietary fiber, lactulose, lactitol, or raffinose which are hardly decomposable oligosaccharides can be used. At present, it is known that the physiological function of the refractory oligosaccharide is that after the undigested matter reaches the large intestine, Bifidobacterium in the intestine is activated and proliferated, and the intestinal environment is improved, that is, it has an intestinal regulating effect. Lactulose is a synthetic disaccharide formed from galactose and fructose, which is the basic drug for hyperammonemia (Bircher, J. et al., Lancet i: 890, 1965). Recurrent chronic hepatic encephalopathy of chronic liver failure has a good response to lactulose administration, special amino acid drip (Fischer solution) for liver dysfunction, and the like. The second-generation lactulose "lactose" (β-galactosyl-sorbitol) has the same clinical effect on chronic hepatic encephalopathy as lactulose (Lanthier, PL. And Morgan, M., Gut, 26: 415, 1985; Uribe, M., et al., Dig. Dis. Sci., 32: 1345, 1987; Heredia, D. et al., J. Hepatol, 7: 106, 1988; Riggio, 0., et al., Dig. Dis Sci., 34: 823, 1989), is now used as a treatment for hyperammonemia.

其他的水溶性膳食纖維的候選物，例如，具改善脂質代謝作用(降低膽固醇或中性脂肪)的果膠(原果膠、果膠酯酸、果膠酸)、瓜爾豆膠‧酵素分解物、羅晃子膠(tamarind seed gum)等。瓜爾豆膠分解物已知抑制血糖上升作用及減少胰島素的分泌。(大和谷一彥等、日本營養/食糧學會誌，46: 199,1993)。水溶性膳食纖維的候選物還包括，高分子水溶性膳食纖維例如，蒟蒻葡甘聚醣、褐藻酸、低分子褐藻酸、洋車前子、***膠、海藻多糖類(纖維素、木質素類物質、洋菜、卡拉膠、褐藻酸、藻寡醣、海帶多糖)、微生物膠(汶萊膠、熱凝膠、黃原膠、結冷膠、葡聚醣、茁黴多醣、鼠李糖膠)、其他膠類(由種子產生之刺槐豆膠、羅望子膠、塔拉膠、由樹液產生之卡拉亞膠、西黃耆膠)等、低分子水溶性膳食纖維之聚葡萄糖、難分解性糊精、麥芽糖醇等。Other water-soluble dietary fiber candidates, for example, pectin (pro pectin, pectin ester acid, pectin acid), guar gum, enzyme degradation with improved lipid metabolism (lower cholesterol or neutral fat) Objects, tamarind seed gum, etc. Guar gum breakdown products are known to inhibit blood glucose elevation and reduce insulin secretion. (Iwahiko Yamato, et al., Journal of the Japanese Nutrition / Food Association, 46: 199, 1993). Candidates for water-soluble dietary fiber also include high-molecular-weight water-soluble dietary fiber such as glucomannan, alginic acid, low-molecular-weight alginic acid, psyllium seed, acacia, seaweed polysaccharides (cellulose, lignin Substances, agar, carrageenan, alginic acid, algal oligosaccharides, kelp polysaccharides, microbial gums (Brunei gum, thermogels, xanthan gum, gellan gum, dextran, saccharin polysaccharide, rhamnosin ), Other gums (locust bean gum, tamarind gum, tara gum, karaya gum, tragacanth gum produced from sap), etc., low-molecular-weight water-soluble dietary fiber, polydextrose, difficult to decompose Dextrin, maltitol, etc.

不溶性膳食纖維增加大腸中不消化物質的重量，縮短通過的時間。其結果導致排便次數及便量增加。不溶性膳食纖維的候選物，例如纖維素、半纖維素、木質素、幾丁質、殼聚醣、大豆膳食纖維、小麥麩、松纖維、玉米纖維、甜菜纖維等。Insoluble dietary fiber increases the weight of indigestible substances in the large intestine and shortens the passage time. As a result, the number of defecations and the amount of defecation are increased. Candidates for insoluble dietary fiber, such as cellulose, hemicellulose, lignin, chitin, chitosan, soybean dietary fiber, wheat bran, pine fiber, corn fiber, beet fiber, and the like.

維生素類包括，例如維生素A、胡蘿蔔素類、維生素E群、維生素C、維生素D群、維生素B、維生素K群、維生素P、維生素Q、菸鹼酸、菸酸、泛酸、生物素、肌醇、膽鹼、葉酸等。Vitamins include, for example, vitamin A, carotene, vitamin E group, vitamin C, vitamin D group, vitamin B, vitamin K group, vitamin P, vitamin Q, nicotinic acid, nicotinic acid, pantothenic acid, biotin, inositol , Choline, folic acid, etc.

目前維生素已知有13種。已知與肝臟有高度相關的維生素為維生素A、B群(B1、B2、菸酸、B6、泛酸、葉酸、B12、生物素)及K。與肝臟損害相關中，維生素A缺乏症及過剩症、維生素E群的缺乏症、維生素K的過剩症為主要問題。There are currently 13 known vitamins. Vitamins known to be highly related to the liver are vitamins A, B (B1, B2, niacin, B6, pantothenic acid, folic acid, B12, biotin) and K. In relation to liver damage, vitamin A deficiency and excess, vitamin E group deficiency, and vitamin K excess are major problems.

維生素A因閉塞性黃疸等腸道內膽汁分泌不足及吸收率下降而引起缺乏。在低蛋白質營養狀態下，視黃醇結合蛋白(RBP)的生成下降，因此無法將維生素A輸送至目標器官中，呈現缺乏症狀。在非代償性肝硬化等的情形，發現相對少量之維生素A過剩所引起的中毒症狀。慢性肝病中已知維生素B群的利用障礙。由於維生素K可由腸內細菌合成，因此通常不會導致缺乏症，但在閉塞性黃疸等中腸道內膽汁不足時，使吸收率下降。Vitamin A is deficient due to insufficient bile secretion and decreased absorption in the intestinal tract such as occlusive jaundice. In the low-protein nutrition state, the production of retinol-binding protein (RBP) is reduced, so vitamin A cannot be delivered to the target organs, showing symptoms of deficiency. In the case of non-compensated cirrhosis, symptoms of poisoning caused by a relatively small amount of excess vitamin A are found. Disturbances in the utilization of the vitamin B group are known in chronic liver disease. Vitamin K is usually synthesized by bacteria in the intestine, so it usually does not cause deficiency, but when there is insufficient bile in the intestinal tract such as occlusive jaundice, the absorption rate decreases.

礦物質類例如鈣，鉀、鎂、鈉、銅、鐵、錳、鋅、硒等。有機酸可使用例如蘋果酸、檸檬酸、乳酸、酒石酸等。Minerals such as calcium, potassium, magnesium, sodium, copper, iron, manganese, zinc, selenium and the like. As the organic acid, for example, malic acid, citric acid, lactic acid, tartaric acid, and the like can be used.

在進行體液管理時通常會發生問題之電解質為鈉、氯、鉀、磷、鈣及鎂。在調配礦物質的配方時，應考慮以下3點：(1)進入細胞內之礦物質是否充分分配，(2)欲投予之營養物質的種類與量是否可與患者內分泌環境充分配合，(3)對腎臟的滲透壓物質的負荷量之推測及為了維持適當尿滲透壓的水分投予量如何。The electrolytes that usually cause problems when managing body fluids are sodium, chlorine, potassium, phosphorus, calcium, and magnesium. When formulating minerals, the following three points should be considered: (1) whether the minerals that enter the cell are fully distributed, (2) whether the type and amount of nutrients to be administered can fully cooperate with the patient's endocrine environment, ( 3) Estimation of the load of the osmotic substance in the kidney and how much water is used to maintain an appropriate osmotic pressure in the urine.

鐵、或其他來自天然物之微量元素，例如含有礦物酵母之銅、鋅、硒、錳、鉻等可含有。也可使用葡萄糖酸銅、葡萄糖酸鋅等。Iron, or other trace elements derived from natural materials, such as copper, zinc, selenium, manganese, chromium, etc., which contain mineral yeast. Copper gluconate, zinc gluconate and the like can also be used.

有機酸例如蘋果酸、檸檬酸、乳酸、酒石酸等。Organic acids such as malic acid, citric acid, lactic acid, tartaric acid and the like.

這些額外添加的營養成份，可為化學合成或來自天然物質的成分。或者，也可將含目的成分的食品作為原料而調配。這些成分可調配至少1種，或2種以上之組合。組成物的形態可為固體或液體皆可。也可為膠狀或半固體狀等。These additional nutrients can be chemically synthesized or derived from natural substances. Alternatively, a food containing a target component may be prepared as a raw material. These ingredients can be mixed with at least one kind or a combination of two or more kinds. The composition may be in the form of a solid or a liquid. It may be in a gel or semi-solid state.

本發明之組成物可利用流質食物或經腸營養劑之領域中一般習知的方法來製造。例如，可採用將液狀組成物預熱滅菌，充填至無菌容器中的方法(例如，併用UHT殺菌法與無菌操作包裝法之方法)，或在將液狀組成物充填至容器中，與容器一起加熱滅菌的方法(例如，蒸餾法、高壓滅菌法)等。換句話說，組成物的使用形態為液狀時，此組成物之均質化物(殺菌液均質化後之物質)，視需要再於約120～145℃下加熱殺菌約1～10秒，之後冷卻，進行無菌充填，或充填至罐裝容器或軟包裝，進行蒸餾殺菌。因此，組成物的使用形態為粉末時，此均質化物進行例如噴霧乾燥或冷凍乾燥。The composition of the present invention can be produced by a method generally known in the field of liquid food or enteral nutrition. For example, the liquid composition can be pre-heated and sterilized and filled into a sterile container (for example, a method using UHT sterilization and aseptic packaging), or the liquid composition can be filled into the container and the container can be filled with the container. A method of heat sterilization together (for example, distillation, autoclaving), and the like. In other words, when the composition is used in a liquid form, the homogenate of the composition (the material after homogenization of the sterilization liquid) can be heated and sterilized at about 120 to 145 ° C for about 1 to 10 seconds, and then cooled , Sterile filling, or filling into canned containers or flexible packaging, and distillation and sterilization. Therefore, when the composition is used as a powder, the homogenate is subjected to, for example, spray drying or freeze drying.

以下針對本發明進行詳細說明，但本發明並不限定於下述各個形態。本發明中，在製備乳清蛋白時(添加‧混合)，加熱調和，例如，此製備液的溫度(調和溫度)在55℃以下。調和溫度在70℃等高溫時，會導致蛋白質凝固(凝乳化)，調和溫度在2℃等低溫時，則蛋白質會難溶於或分散至水等。因此，調和程序的溫度較佳為5～55℃，更佳為40～55℃，更佳為40～53℃，最佳為40～50℃。此時，考量調和液中細菌(污染菌等)的增殖，較佳選用適當的調和時間。Hereinafter, the present invention will be described in detail, but the present invention is not limited to the following embodiments. In the present invention, when whey protein is prepared (added and mixed), the temperature is adjusted by heating. For example, the temperature of the preparation solution (reconciliation temperature) is 55 ° C or lower. When the mixing temperature is at a high temperature, such as 70 ° C, the protein will coagulate (coagulate and emulsify). When the mixing temperature is at a low temperature, such as 2 ° C, the protein will be difficult to dissolve or disperse in water. Therefore, the temperature of the blending program is preferably 5 to 55 ° C, more preferably 40 to 55 ° C, still more preferably 40 to 53 ° C, and most preferably 40 to 50 ° C. At this time, considering the proliferation of bacteria (contaminating bacteria, etc.) in the reconciliation solution, an appropriate reconstitution time is preferably selected.

再者，本發明中調和液在高溫殺菌後，進行均質化。雖然高溫殺菌(加熱)會使得蛋白質變性，黏度增加(增黏)，但高溫殺菌後進行均質化可降低增黏程度。此處，高溫殺菌後進行的均質化為，在高溫殺菌後，充填至容器等製品之前，進行均質化，不限於1次，也可為2次以上等複數次。例如，調和液在殺菌後，直接進行第2次的殺菌步驟時，在此第2次的殺菌步驟後也進行均質化程序。又調和液在殺菌後進行均質化，且在第2次的殺菌步驟時，此第2次的殺菌步驟之後，再進行第2次的均質化。因此，調和液殺菌後進行均質化，也可在不殺菌而再進行第2次均質化。本發明中，調和液在高溫殺菌後，充填至容器等形成產品之前，即使只是1次的均質化步驟也非常重要。Furthermore, in the present invention, the blending liquid is homogenized after being sterilized at a high temperature. Although high-temperature sterilization (heating) will denature proteins and increase viscosity (thickening), homogenization after high-temperature sterilization can reduce the degree of viscosity increase. Here, the homogenization performed after the high-temperature sterilization is performed after the high-temperature sterilization and before filling into a product such as a container. The homogenization is not limited to one time, and may be a plurality of times such as two or more times. For example, when the blending solution is directly sterilized and then subjected to the second sterilization step, a homogenization procedure is also performed after the second sterilization step. After the sterilization solution is homogenized, the second homogenization step is performed after the second sterilization step. Therefore, after the sterilizing liquid is homogenized, the second homogenization may be performed without sterilization. In the present invention, it is very important that the blending solution is homogenized only once after being sterilized at a high temperature and before being filled into a container or the like to form a product.

另一方面，高溫殺菌之調和液(殺菌液)在進行均質化後，可在殺菌液不增黏的情況下，再進行殺菌步驟。例如，調和液在殺菌後進行均質化，可不高溫殺菌而重新在第2次殺菌。此時，高溫殺菌步驟相當為例如溫度100～150℃，維持時間1～30秒之熱履歷，較佳為115～145℃，維持時間1～20秒，更佳為120～145℃，維持時間1～10秒，最佳為125～140℃，維持時間1～5秒。雖然高溫殺菌容易使蛋白質變性，增加殺菌液的黏度，但是若不進行高溫殺菌則黏度不易增加，因此均質化使黏度降低的效果，在高溫殺菌中特別地表現。On the other hand, after the homogenization solution (sterilization solution) for high-temperature sterilization is homogenized, the sterilization step can be performed without the sterilization solution thickening. For example, after the sterilization solution is homogenized, the second sterilization can be performed without sterilizing at high temperature. At this time, the high-temperature sterilization step is, for example, a thermal history with a temperature of 100 to 150 ° C and a holding time of 1 to 30 seconds, preferably 115 to 145 ° C, a holding time of 1 to 20 seconds, and more preferably 120 to 145 ° C and a holding time 1 to 10 seconds, preferably 125 to 140 ° C, and a holding time of 1 to 5 seconds. Although high-temperature sterilization can easily denature proteins and increase the viscosity of the sterilization solution, the viscosity is not easily increased without high-temperature sterilization. Therefore, the effect of homogenization to reduce the viscosity is particularly exhibited in high-temperature sterilization.

在進行高溫殺菌時，也可調整調和液的壓力(加壓或減壓)。此時，通常是為了防止調和液沸騰等目的，例如，殺菌壓力為1～10kg/cm²的程度。也就是說，本發明之高溫殺菌中，除了溫度(加熱)以外，也可增加如上述的壓力。高溫殺菌的裝置例如，平板式熱交換器、管式熱交換器、蒸氣注入(injection)式殺菌機、蒸氣注射(infusion)式殺菌機、通電加熱式殺菌機等。另一方面，在使用均質機進行均質化程序時，例如將溫度設定為約10～60℃、流量設定為約100～10000L/h時，壓力可為10～100MPa，較佳為20～80MPa，更佳為30～70MPa，最佳為20～50MPa。若有必要，可改變高溫殺菌或均質化的操作條件，也可進行複數次的處理。When performing high-temperature sterilization, the pressure (pressurization or decompression) of the conditioning liquid can also be adjusted. In this case, it is usually for the purpose of preventing boiling of the blending liquid, for example, the sterilization pressure is about 1 to 10 kg / cm ² . That is, in the high-temperature sterilization of the present invention, in addition to the temperature (heating), the pressure as described above can be increased. The high-temperature sterilization device is, for example, a flat plate heat exchanger, a tube heat exchanger, a steam injection sterilizer, a steam injection sterilizer, an electric heating sterilizer, or the like. On the other hand, when a homogenization program is performed using a homogenizer, for example, when the temperature is set to about 10 to 60 ° C. and the flow rate is set to about 100 to 10000 L / h, the pressure may be 10 to 100 MPa, preferably 20 to 80 MPa. It is more preferably 30 to 70 MPa, and most preferably 20 to 50 MPa. If necessary, the operating conditions of high-temperature sterilization or homogenization can be changed, and multiple treatments can be performed.

以下針對本發明列舉詳細的例子說明，但因此限定本發明。調和步驟為在槽內預先攪拌上述溫度的溫水，考慮容易混合/擴散，依序添加、混合、攪拌維生素混合物(維生素的混合成分)以外的原料，以形成調和液。將原料依容易混合、擴散的添加順序因原料的量或特性而異，可一次或分成各種順序添加，例如以糖、蛋白質、油脂、礦物質的順序添加的方法。在另一例子中，以部分的糖、蛋白質、其他糖類、礦物質、油脂的順序添加的方法。又在另一例子中，以油脂、蛋白質、糖、礦物質的順序添加的方法。此調和液在以蒸氣注入(injection)法加熱殺菌後，以均質機進行均質化(以二階段的壓力均質化)，形成殺菌液。將維生素混合物(維生素的混合成分)及調味料(香料)等添加、混合至殺菌液中，形成最終的殺菌液。將此最終殺菌液再以蒸氣注射(infusion)法加熱殺菌(二階段殺菌)後，以均質機進行均質化(以二階段壓力進行均質化)，獲得組成物。Hereinafter, the present invention will be described in detail by way of examples, but the present invention is limited thereto. The blending step is to stir warm water at the above temperature in the tank in advance, considering easy mixing / diffusion, and sequentially adding, mixing, and stirring raw materials other than the vitamin mixture (mixed component of vitamins) to form a blending solution. The order in which the raw materials are easily mixed and diffused varies depending on the amount or characteristics of the raw materials, and can be added at once or in various orders, such as a method of adding sugar, protein, oil, and minerals in that order. In another example, a method of adding a part of sugar, protein, other sugars, minerals, and fats in that order. In another example, a method of adding fat, protein, sugar, and minerals in that order. This blending liquid is heated and sterilized by a vapor injection method, and then homogenized (homogenized by two-stage pressure) with a homogenizer to form a sterilization liquid. A vitamin mixture (mixed component of vitamins), seasoning (fragrance), and the like are added and mixed into the sterilizing solution to form a final sterilizing solution. This final sterilization solution was heated and sterilized by a steam injection method (two-stage sterilization), and then homogenized by a homogenizer (homogenized by two-stage pressure) to obtain a composition.

用於促進小腸絨毛生長、增加小腸肌肉層厚度、改善腸道功能、預防小腸組織損害、以及治療各種炎症，依據症狀、體重等而有所不同，例如，在作為飲食品投予(攝取)時，投予量一般為每日約0.05g～約1000g的固形分含量，較佳為約0.05g～約250g，更佳為約2.5g～約50g。對於必須投予本發明組成物的對象，可一次或分成飯前、飯後、飯間及/或睡前適當投予。投予量個別依投予者的年齡、體重、及投予目的適當調節。本發明之組成物也可作為代餐，或食品補充物。It is used to promote the growth of small intestine villi, increase the thickness of the small intestine muscle layer, improve intestinal function, prevent damage to small intestine tissues, and treat various inflammations. It varies depending on symptoms, weight, etc., for example, when administered as a food or drink The dosage is generally about 0.05g to about 1000g of solid content per day, preferably about 0.05g to about 250g, more preferably about 2.5g to about 50g. The subject who must administer the composition of the present invention can be administered appropriately at one time or before meals, after meals, between meals, and / or before bedtime. The amount of administration is appropriately adjusted depending on the age, weight, and purpose of administration. The composition of the present invention can also be used as a meal replacement or food supplement.

本發明組成物若為酸性醫藥品或食品的型態時，其pH值為pH2.0～pH6.0，較佳為pH3.0～pH5.0。When the composition of the present invention is in the form of an acidic pharmaceutical or food, its pH value is pH 2.0 to pH 6.0, and preferably pH 3.0 to pH 5.0.

上述本發明組成物之用途，如以下(1)～(30)所述。The use of the composition of the present invention is as described in the following (1) to (30).

(1)促進小腸絨毛生長的方法，包括投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖的組成物。(1) A method for promoting the growth of small intestine villi, comprising administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a sugar.

(2)增加小腸肌肉層厚度的方法，包括投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖的組成物。(2) A method for increasing the thickness of the small intestine muscle layer, comprising administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a sugar.

(3)改善腸道功能的方法，包括投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖的組成物。(3) A method for improving intestinal function, comprising administering a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, lipid as oil and fat, and isomaltulose as sugar.

(4)預防小腸組織損害的方法，包投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖的組成物。(4) A method for preventing damage to the small intestine tissue by administering a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, fat and oil as lipid, and isomaltulose as sugar.

(5)抑制發炎的方法，包括投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖的組成物。(5) A method for suppressing inflammation, comprising administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat or oil as a lipid, and an isomaltulose as a sugar.

(6)在製造促進小腸絨毛生長之組成物中，使用含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖的組成物之使用。(6) Use of a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, lipid as oil and fat, and isomaltulose as a saccharide in manufacturing a composition for promoting intestinal villus growth .

(7)在製造使小腸肌肉層厚度增加的組成物中，使用含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖的組成物之使用。(7) In a composition for increasing the thickness of the small intestine muscle layer, a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a sugar Its use.

(8)在製造改善腸道功能的組成物中，使用含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖的組成物之使用。(8) Use of a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk as a lipid, an oil and fat, and a composition containing isomaltulose as a saccharide in the manufacture of a composition for improving intestinal function. .

(9)在製造預防小腸組織損害的組成物中，使用含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖的組成物之使用。(9) Use of a composition containing milk protein hydrolysate as protein and protein derived from fermented milk, lipid as oil and fat, and isomaltulose as carbohydrate in a composition for preventing intestinal tissue damage .

(10)在製造抗發炎的組成物中，使用含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖的組成物之使用。(10) Use of a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat and oil as a lipid, and an isomaltulose as a sugar in an anti-inflammatory composition.

(11)用於促進小腸絨毛生長的方法之組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。(11) A composition for a method for promoting the growth of small intestinal villi, comprising a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat as a lipid, and an isomaltulose as a sugar.

(12)用於使小腸肌肉層厚度增加的方法之組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。(12) A composition for a method for increasing the thickness of the small intestinal muscle layer, comprising a milk protein hydrolysate as a protein and a protein derived from fermented milk, an oil as a lipid, and isomaltulose as a sugar.

(13)用於改善腸道功能的方法之組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。(13) A composition for a method for improving intestinal function, including a milk protein hydrolysate of protein and protein derived from fermented milk, a fat and oil as lipid, and isomaltulose as a sugar.

(14)用於預防小腸組織損害的方法之組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。(14) A composition for a method for preventing damage to a small intestine tissue, comprising a milk protein hydrolysate as a protein and a protein derived from fermented milk, a fat as a lipid, and an isomaltulose as a sugar.

(15)用於抑制發炎的方法之組成物，包括作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，作為脂質之油脂，以及作為糖類之異麥芽酮糖。(15) A composition for a method for suppressing inflammation, including a milk protein hydrolysate of protein and protein derived from fermented milk, oils and fats as lipids, and isomaltulose as a sugar.

(16)改善腸道功能的方法，包括投予含有源自醱酵乳之蛋白質之組成物的步驟。(16) A method for improving intestinal function, comprising the step of administering a composition containing protein derived from fermented milk.

(17)改善腸道功能的方法，包括投予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，以及作為糖類之異麥芽酮糖之組成物的步驟。(17) A method for improving intestinal function, comprising the step of administering a composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a sugar.

(18)預防小腸組織損害的方法，包括給予含有源自醱酵乳之蛋白質之組成物的步驟。(18) A method for preventing damage to small intestine tissue, comprising the step of administering a composition containing protein derived from fermented milk.

(19)預防小腸組織損害的方法，包括給予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，以及作為糖類之異麥芽酮糖之組成物的步驟。(19) A method for preventing damage to the small intestine tissue, comprising the step of administering a composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a sugar.

(20)抑制發炎的方法，包含給予含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質之組成物的步驟。(20) A method for suppressing inflammation, comprising the step of administering a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk.

(21)源自醱酵乳之蛋白質用於製造改善腸道功能之組成物的使用。(21) Use of a protein derived from fermented milk for producing a composition for improving intestinal function.

(22)乳蛋白質水解物及源自醱酵乳之蛋白質之蛋白質，以及異麥芽酮糖之糖類用於製造改善腸道功能之組成物的使用。(22) Use of a milk protein hydrolysate and a protein derived from fermented milk, and isomaltulose sugars for producing a composition that improves intestinal function.

(23)源自醱酵乳之蛋白質用於製造預防小腸組織損害的組成物的使用。(23) Use of a protein derived from fermented milk for producing a composition for preventing damage to small intestine tissue.

(24)含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，以及作為糖類之異麥芽酮糖的組成物用於製造預防小腸組織損害之組成物的使用。(24) Use of a composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a saccharide to prevent damage to small intestine tissue.

(25)含作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質之組成物用於製造抗發炎組成物的使用。(25) Use of a composition containing a milk protein hydrolysate as a protein and a protein derived from fermented milk for producing an anti-inflammatory composition.

(26)含源自醱酵乳之蛋白質之組成物，使用於改善腸道功能的方法。(26) A composition containing fermented milk-derived protein, which is used to improve intestinal function.

(27)含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，以及作為糖類之異麥芽酮糖的組成物，使用於改善腸道功能的方法。(27) A composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a saccharide, which is used for a method for improving intestinal function.

(28)含源自醱酵乳之蛋白質之組成物，使用於預防小腸組織損害的方法。(28) A composition containing protein derived from fermented milk and used for preventing small intestinal tissue damage.

(29)含有作為蛋白質之乳蛋白質水解物及源自醱酵乳之蛋白質，以及作為糖類之異麥芽酮糖的組成物，使用於預防小腸組織損害的方法。(29) A composition containing a milk protein hydrolysate as a protein, a protein derived from fermented milk, and isomaltulose as a saccharide, which is used for a method for preventing damage to small intestine tissue.

(30)含有乳蛋白質水解物及源自醱酵乳之蛋白質之組成物，使用於抑制發炎的方法。(30) A composition containing a milk protein hydrolysate and a protein derived from fermented milk, and used for a method for suppressing inflammation.

本發明組成物可為，例如MEIN(明治乳業株式會社)。含MEIN成分之組成物為含表4記載成分的組成物。The composition of the present invention may be, for example, MEIN (Meiji Dairy Co., Ltd.). The composition containing a MEIN component is a composition containing the components described in Table 4.

表4的脂肪中，牛奶磷脂質(又稱為乳源性磷脂質、牛奶卵磷脂)的組成例如表5所示。Table 5 shows the composition of milk phospholipids (also referred to as milk-derived phospholipids and milk lecithin) in the fat in Table 4.

表4之脂肪中，脂肪酸的組成例如表6所示。Examples of the fatty acid composition in Table 4 are shown in Table 6.

本發明說明書中所引用之所有的先前技術文獻皆納入本發明說明書中。All prior art references cited in the present specification are incorporated into the present specification.

【實施例】[Example] [實施例1][Example 1] 營養組成物的小腸組織損害減輕效果(1)Small intestinal tissue damage reduction effect of nutritional composition (1)

本發明之營養組成物及作為對照組之一般流體食物(Maibalance：明治乳業(株))、流體食物A(Impact：味之素製藥(株))進行試驗，在投予ConA 24小時後，檢測小腸組織的損害程度。The nutritional composition of the present invention and general fluid food (Maibalance: Meiji Dairy Co., Ltd.) and fluid food A (Impact: Ajinomoto Pharmaceutical Co., Ltd.) as a control group were tested, and tested after 24 hours of administration to ConA Degree of damage to small intestine tissue.

使用購自日本SLC(株)的C57BL/6小鼠(6週齡，雄)。飼養環境為21.0±2.0℃，濕度55.0±15.0%，每12小時切換明暗(光照期：7-19點)。實驗期間，飼料及飲水可自由攝取。C57BL / 6 mice (6 weeks old, male) purchased from Japan SLC Co., Ltd. were used. The breeding environment is 21.0 ± 2.0 ° C, and the humidity is 55.0 ± 15.0%, and the light and dark are switched every 12 hours (lighting period: 7-19 points). During the experiment, feed and water were freely available.

購買的動物在經1個星期的馴化後的體重為指標，分成3群。實驗群為：第1群：一般流體食物(明治乳業：Maibalance)，第2群：營養組成物(明治乳業：MEIN)，第3群：流體食物A(味之素製藥：IMPACT)，進行2週的飼養。一般流體食物、營養組成物、流體食物A的組成如表7及表8所示。本實施例中所使用之異麥芽酮糖的CAS註冊號第13718-94-0號，化學式C₁₂H₂₂O₁₁所示之物質。The body weight of the purchased animals after one week of domestication was used as an index and divided into three groups. The experimental groups are: Group 1: General fluid food (Meiji Dairy: Maibalance), Group 2: Nutritional composition (Meiji Dairy: MEIN), Group 3: Fluid Food A (Ajinomoto Pharmaceutical: IMPACT), perform 2 Week of feeding. The composition of general fluid food, nutritional composition, and fluid food A is shown in Table 7 and Table 8. The isomaltulose used in this example is a substance having a CAS registration number of 13718-94-0 and a chemical formula of C ₁₂ H ₂₂ O ₁₁ .

將12mg/kg的ConA(Sigma)由尾靜脈投予，投予24小時後，***麻醉，由腹部大靜脈採血後，將小腸取出。小腸為胃的下方6 cm至3 cm處，以10%福馬林溶液固定後，以一般的方法進行包埋，製作組織標本，以蘇木精-尹紅進行染色。利用數位顯微鏡(Keyence公司)，100倍攝影組織標本，測量影像中含絨毛之黏膜層與肌肉層的所有面積。結果以平均值±SD(n=7～9)顯示。統計分析以SPSS進行單因子變異數分析後，經Scheffe檢定，p<0.05代表有顯著差異。12 mg / kg of ConA (Sigma) was administered through the tail vein, 24 hours after the administration, anesthesia was performed with ether, blood was collected from the large abdominal vein, and the small intestine was removed. The small intestine is 6 cm to 3 cm below the stomach, fixed with 10% formalin solution, and then embedded in general methods to prepare tissue samples and stained with hematoxylin-yin red. Using a digital microscope (Keyence), 100 times photographed tissue specimens to measure the entire area of the villi-containing mucosal layer and muscle layer in the image. Results are shown as mean ± SD (n = 7-9). Statistical analysis After SPSS analysis of single-factor mutations, Scheffe's test showed that p <0.05 represented a significant difference.

結果如第1、2圖所示。比較小腸面積的結果發現，營養組成物攝取群顯示最高值，其餘依序為一般流體食物攝取群、流體食物A攝取群(第1圖)。營養組成物攝取群與流體食物A攝取群之間有顯著差異。由第2圖所示之組織圖可知，投予ConA會造成小腸黏膜上皮的損傷、脫落或肌肉層厚度降低等傷害。另一方面，與正常組織圖相近者為營養組成物攝取群(第2圖)，由此結果可知，攝取營養組成物可減輕小腸的損害程度。The results are shown in Figures 1 and 2. As a result of comparing the area of the small intestine, it was found that the nutrient composition intake group showed the highest value, and the rest were the general fluid food intake group and the fluid food A intake group in order (Figure 1). There is a significant difference between the nutrient composition intake group and the fluid food A intake group. From the tissue chart shown in Figure 2, it can be seen that administration of ConA will cause damage to the small intestinal mucosa epithelium, fall off, or decrease in muscle layer thickness. On the other hand, those close to the normal tissue map are the nutrient composition intake group (Figure 2). From this result, it can be seen that the intake of the nutritional composition can reduce the degree of damage to the small intestine.

[實施例2][Example 2] 營養組成物的小腸組織損害減輕效果(2)Small intestinal tissue damage reduction effect of nutritional composition (2)

利用本發明之營養組成物及作為對照組之Maibalance進行試驗，在投予ConA 2小時後，分析小腸中細胞激素的產生，並評估24小時後組織的損害程度。The nutritional composition of the present invention and Maibalance as a control group were used for testing. Two hours after administration of ConA, the production of cytokines in the small intestine was analyzed, and the degree of tissue damage after 24 hours was evaluated.

使用購自日本SLC(株)的C57BL/6小鼠(6週大，雄)。飼養環境為21.0±2.0℃，濕度55.0±15.0%，每12小時切換明暗(光照期：7-19點)。實驗期間，飼料及飲水可自由攝取。C57BL / 6 mice (6 weeks old, male) purchased from Japan SLC Co., Ltd. were used. The breeding environment is 21.0 ± 2.0 ° C, and the humidity is 55.0 ± 15.0%, and the light and dark are switched every 12 hours (lighting period: 7-19 points). During the experiment, feed and water were freely available.

將購買的動物在經1個星期的馴化後的體重為指標，分成4群。實驗群為，第1群：一般流體食物(ConA投予2小時後解剖)、第2群：營養組成物(ConA投予2小時後解剖)、第3群：一般流體食物(ConA投予24小時後解剖)、第4群：營養組成物(ConA投予24小時後解剖)，進行2週的飼養。所使用的一般流體食物及營養組成物與實施例1相同。The body weight of the purchased animals after domestication for one week was used as an index and divided into 4 groups. The experimental group is: group 1: general fluid food (dissected 2 hours after ConA administration), group 2: nutritional composition (dissection 2 hours after ConA administration), group 3: general fluid food (ConA administration 24 Dissected after hours), group 4: nutritional composition (dissected 24 hours after ConA administration), and reared for 2 weeks. The general fluid food and nutritional composition used were the same as in Example 1.

將12mg/kg的ConA(Sigma)由尾靜脈投予，在投予2小時與24小時後，***麻醉，由腹部大靜脈採血後，摘取肝臟、脾臟、小腸、大腸。測量小腸全長的長度，胃下方11cm至10 cm的重量、大腸(盲腸下5 cm)的重量。測量各臟器的重量。將小腸由胃的下方6cm至3cm切出，以10%的福馬林溶液固定後，以一般的方法進行包埋，製作組織標本，並進行蘇木精-尹紅染色。將臟器中的細胞激素以下述方法調整後，利用Mouse inflammat ion套組(CBA法：日本Becton，Dickinson(株))進行檢測，結果以每臟器之單位重量的濃度表示。結果以平均值±SD表示。統計結果以SPSS進行單因子變異數分析後，經Student’s t檢定或Mann-Whitney檢定。12 mg / kg of ConA (Sigma) was administered through the tail vein. After 2 and 24 hours of administration, anesthetized with ether, blood was collected from the abdominal large vein, and the liver, spleen, small intestine, and large intestine were removed. Measure the length of the small intestine, the weight of 11 cm to 10 cm below the stomach, and the weight of the large intestine (5 cm below the cecum). Measure the weight of each organ. The small intestine was cut out from 6 cm to 3 cm below the stomach, fixed with a 10% formalin solution, and then embedded in a general method to prepare a tissue specimen and perform hematoxylin-yin red staining. The cytokines in the organs were adjusted in the following manner, and then detected using a Mouse inflammat ion kit (CBA method: Becton, Dickinson Co., Ltd., Japan). The results were expressed as a concentration per unit weight of the organs. Results are expressed as mean ± SD. The statistical results were analyzed by single factor variation with SPSS, and then Student's t test or Mann-Whitney test.

<臟器中細胞激素濃度的檢測方法><Detection method of cytokine concentration in organs>

1.將1 ml的分解緩衝液(lysis buffer)加至100 mg的臟器中，以Glass‧Teflon(註冊商標)均質機進行均質化。1. Add 1 ml of lysis buffer to 100 mg of organs and homogenize with a Glass‧Teflon (registered trademark) homogenizer.

分解緩衝液Decomposition buffer

20mM Tris‧HCl(pH7.4)20mM Tris‧HCl (pH7.4)

0.25M蔗糖0.25M sucrose

2mM EDTA‧2Na2mM EDTA‧2Na

10mM EGTA10mM EGTA

1% Tritonx-1001% Tritonx-100

+1個Complete Mine protease inhibitor cocktail錠片/10ml+1 Complete Mine protease inhibitor cocktail tablets / 10ml

2.將均質化的均質物以100,000g轉，離心40分鐘，收集上清液(於冰冷中操作)。2. The homogenized homogenate was rotated at 100,000 g, centrifuged for 40 minutes, and the supernatant was collected (operating in ice cooling).

3.以BCA蛋白質分析法檢測上清液中蛋白質的濃度。每單位蛋白質的細胞激素含量與檢測血漿中細胞激素的方法相同檢測。3. BCA protein assay was used to detect the protein concentration in the supernatant. The cytokine content per unit of protein is measured in the same way as for cytokines in plasma.

(參考文獻：Journal of Neuroinflammation 2008,5:10,Increased systemic and brain cytokine production and neuroinflammation by endotoxin following ethanol treatment Liya Qin,Jun He,Richard N Hanes,Olivera Pluzarev,Jau-Shyoung Hong and Fulton T Crews)(References: Journal of Neuroinflammation 2008, 5:10, Increased systemic and brain cytokine production and neuroinflammation by endotoxin following ethanol treatment Liya Qin, Jun He, Richard N Hanes, Olivera Pluzarev, Jau-Shyoung Hong and Fulton T Crews)

結果如表9～11所示。The results are shown in Tables 9 to 11.

各群組間的體重無差異。一方面顯示小腸、大腸的重量顯著地增加。腸的長度也顯示顯著地長(表9)。There was no difference in body weight between groups. On the one hand, the weight of the small intestine and large intestine was significantly increased. The length of the intestine was also shown to be significantly longer (Table 9).

其次顯示血漿中及臟器中細胞激素濃度的檢測結果(表10)。血漿中細胞激素或趨化因子TNF-α、IFN-γ、MCP-1、IL-6的濃度在一般流體食物群中顯著地上升，而在營養組成物群中均顯示顯著的低值。IL-12與IL-10的濃度在檢測極限以下。臟器中的細胞激素主要於脾臟中產生，與一般流體食物群的濃度相比，營養組成物群中IFN-γ、MCP-1、IL-6的濃度顯示顯著地低值。與一般流體食物群相比，營養組成物群之肝臟中TNF-α(p=0.07)、IFN-γ、MCP-1顯示顯著的低值。小腸中的MCP-1、IL-6顯示顯著的低值。已知ConA明顯引起肝臟的損害，而營養組成物群抑制肝臟損害，顯示與抑制肝臟中TNF-α的生成有關。由於血漿中IL-6濃度的上昇無法僅以肝臟中IL-6的濃度解釋，可能與脾臟中的產生量有關。與其他臟器相比，小腸中發炎性細胞激素的濃度較低，與正常濃度相比，MCP-1與IL-6的濃度較高，與一般流體食物群相比，營養組成物群顯示顯著的低值，因此認為與損害的減輕有關。The results of cytokine concentrations in plasma and organs are shown next (Table 10). The concentrations of cytokines or chemokines TNF-α, IFN-γ, MCP-1, and IL-6 in the plasma significantly increased in the general fluid food group, but all showed significant low values in the nutrient composition group. The concentrations of IL-12 and IL-10 are below the detection limit. Cytokines in the organs are mainly produced in the spleen, and the concentrations of IFN-γ, MCP-1, and IL-6 in the nutrient composition group show significantly lower values than the concentration of the general fluid food group. Compared with the general fluid food group, TNF-α (p = 0.07), IFN-γ, and MCP-1 in the liver of the nutrient composition group showed significantly lower values. MCP-1 and IL-6 in the small intestine showed significantly low values. It is known that ConA obviously causes liver damage, and the nutrient composition group inhibits liver damage, which has been shown to be related to the inhibition of TNF-α production in the liver. Since the increase in IL-6 concentration in plasma cannot be explained solely by the concentration of IL-6 in the liver, it may be related to the amount produced in the spleen. Compared with other organs, the concentration of inflammatory cytokines in the small intestine is lower. Compared with normal concentrations, the concentrations of MCP-1 and IL-6 are higher. Compared with the general fluid food group, the nutritional composition group shows a significant The low value of is considered to be related to the reduction of damage.

以下顯示在投予ConA 24小時後的小腸病理組織以0～3表示程度進行評估的結果，與一般流體食物群相比，營養組成物群的小腸損害減輕(Mann-whitney檢定，p=0.021)(表11)。The results of the evaluation of the small intestine pathological tissues to the extent of 0 to 3 24 hours after administration of ConA are shown below. The small intestinal damage of the nutrient composition group is reduced compared to the general fluid food group (Mann-whitney test, p = 0.021) (Table 11).

[實施例3][Example 3] 營養組成物的黏膜上皮或肌肉層的增殖促進作用Proliferation of mucosal epithelium or muscle layer of nutritional composition

在自由攝取本發明營養組成物及一般流體食物2週後，進行小腸、大腸的重量、及小腸組織的評估。Two weeks after free ingestion of the nutritional composition of the present invention and general fluid food, the weight of the small intestine, large intestine, and small intestine tissue were evaluated.

將購買的動物在經1個星期的馴化後的體重為指標，每群5隻，分成2群。實驗群為，第1群：一般流體食物、第2群：營養組成物，經2週飼養。一般流體食物及營養組成物與實施例1相同。The body weight of the purchased animals after one week of domestication was used as an index. Five animals in each group were divided into two groups. The experimental group was: Group 1: General fluid food, Group 2: Nutritional composition, and reared for 2 weeks. The general fluid food and nutritional composition are the same as in Example 1.

***麻醉，由腹部大靜脈採血後，摘取肝臟、脾臟、小腸、大腸。測量小腸的全長、胃下方11cm至10cm的重量、盲腸下5cm的大腸重量。測量各臟器的重量。將小腸由胃的下方6cm至3cm切出，以10%的福馬林溶液固定後，以一般的方法進行包埋，製作組織標本，並進行蘇木精-尹紅染色。針對組織標本，檢測血漿中ALT、AST、白蛋白、總蛋白質、三酸甘油酯、膽固醇、葡萄糖、尿素氮的生化檢查。結果以平均值±SD表示。統計結果以SPSS進行單因子變異數分析後，經Student’s t檢定。After anesthesia with ether, blood was collected from the large abdominal vein, and the liver, spleen, small intestine, and large intestine were harvested. The total length of the small intestine, the weight of 11 cm to 10 cm below the stomach, and the large intestine weight of 5 cm below the cecum were measured. Measure the weight of each organ. The small intestine was cut out from 6 cm to 3 cm below the stomach, fixed with a 10% formalin solution, and then embedded in a general method to prepare a tissue specimen and perform hematoxylin-yin red staining. Biochemical examination of ALT, AST, albumin, total protein, triglyceride, cholesterol, glucose and urea nitrogen in tissue samples. Results are expressed as mean ± SD. The statistical results were analyzed by SPSS with single factor variation and then tested by Student's t test.

在攝取一般流體食物與營養組成物的2週期間，正常小鼠的臟器重量與血液生化檢查結果如表12所示。正常小鼠的群組之間，體重、肝臟並無顯著差異。與一般流體食物群相比，營養組成物群之脾臟相對重量、小腸、大腸重量顯示顯著的高值。另一方面，各群組間的所有血液生化檢查結果數值無顯著差異。Table 2 shows the organ weight and blood biochemical examination results of normal mice during the two weeks of ingestion of general fluid food and nutritional composition. There were no significant differences in body weight and liver between normal mouse groups. Compared with the general fluid food group, the relative weight of the spleen, the weight of the small intestine, and the large intestine of the nutritional composition group showed significantly higher values. On the other hand, there was no significant difference in the values of all blood biochemical test results between the groups.

其次，製作正常小腸組織的標本，以150倍攝影分析1視野內的絨毛數、絨毛高度、肌肉層厚度(第3圖及表13)。與一般流體食物群相比，營養組成物群的絨毛數與絨毛全長無顯著差異，但在絨毛的平均長度與肌肉層的厚度上有呈現顯著的高值。由此結果推知，營養組成物群組的小腸重量增加起因於絨毛長度與肌肉層厚度的增加。Next, a specimen of a normal small intestine tissue was prepared, and the number of villi, the height of the villi, and the thickness of the muscle layer in a field of view were analyzed at 150 times a photograph (Figure 3 and Table 13). Compared with the general fluid food group, the number of villi and the total length of the villi of the nutritional composition group were not significantly different, but the average length of the villi and the thickness of the muscle layer showed a significant high value. From this result, it is inferred that the increase in the weight of the small intestine of the nutritional composition group is due to the increase in the length of the villi and the thickness of the muscle layer.

[實施例4][Example 4] 營養組成物的腸道通透性亢進及細菌移位的抑制作用Intestinal hyperpermeability of nutritional composition and inhibition of bacterial translocation

使用引朵美酒辛(indomethacin)誘導之大鼠小腸損害模型來評估本發明營養組成物對小腸損害的影響。A model of intestinal damage in rats induced by indomethacin was used to evaluate the effect of the nutritional composition of the present invention on small intestinal damage.

使用購自日本SLC(株)的SD大鼠(6週大，雄)。飼養環境為21.0±2.0℃，濕度55.0±15.0%，每12小時切換明暗(光照期：7-19點)。實驗期間，飼料及飲水可自由攝取。SD rats (6 weeks old, male) purchased from Japan SLC Co., Ltd. were used. The breeding environment is 21.0 ± 2.0 ° C, and the humidity is 55.0 ± 15.0%, and the light and dark are switched every 12 hours (lighting period: 7-19 points). During the experiment, feed and water were freely available.

將購買的動物在經1個星期的馴化後的體重為指標，分成6群。在投予引朵美酒辛(indomethacin)前的2週，餵食一般流體食物或營養組成物。一般流體食物及營養組成物與實施例1相同。之後，將引朵美酒辛(indomethacin)溶於5% NaHCO₃中，每日皮下注射10mg/kg溶液1次，連續注射2天，以誘發小腸損害。之後，以相同的飼料進行飼養，以投予的第1天定為第0天，在第4天、第8天時解剖檢測。未投予引朵美酒辛(indomethacin)之正常群組，分別於第4天及第8天解剖檢測半數的大鼠。The body weight of the purchased animals after domestication for one week was used as an index and divided into 6 groups. Two weeks before the administration of indomethacin, a general fluid food or nutritional composition was fed. The general fluid food and nutritional composition are the same as in Example 1. Thereafter, indomethacin was dissolved in 5% NaHCO ₃ , and a solution of 10 mg / kg was injected subcutaneously once a day for 2 consecutive days to induce damage to the small intestine. Thereafter, they were reared with the same feed, and the first day of administration was set as the 0th day, and the anatomical examination was performed on the 4th and 8th days. In the normal group without administration of indomethacin, half of the rats were dissected and examined on the 4th and 8th days, respectively.

在第1天、第3天、第7天時，以每隻3ml經口投予0.6%的苯酚磺酞「第一三共」(第一三共(株))後，收集24小時內的尿液，檢測尿中PSP***量，以尿中的PSP***率表示。PSP為一般人類腎功能指標。經口給予PSP時，雖然尿中的***率非常低，但是因腸道膜損害而使通透性亢進，通過細胞隙間進入血液內，透過腎臟***於尿中。在本實施例中使用腸道膜通透性作為指標。On the 1st, 3rd, and 7th days, 0.6% of phenol sulfophthalate "Daisankyo" (Daisankyo Co., Ltd.) was orally administered in 3 ml of each, and collected within 24 hours. Urine, the amount of PSP excretion in the urine was measured, expressed as the rate of PSP excretion in the urine. PSP is a general index of human renal function. When PSP is administered orally, although the excretion rate in urine is very low, the permeability is increased due to damage to the intestinal membrane, it enters the blood through the interstitial space, and is excreted in the urine through the kidney. In the present embodiment, intestinal membrane permeability is used as an index.

從解剖前一天的下午5點開始絕食，在絕食一個晚上後進行解剖檢測。***麻醉，由心臟採血後，在無菌狀態下摘取腸道膜淋巴結(MLN)、肝臟，測量臟器重量後，將臟器均質化的溶液培養於含有5%馬去纖維蛋白血液的BL洋菜培養基，於37℃，好氧及厭氧的條件下培養72小時後，計數菌數。進行革蘭氏染色，調查檢出的細菌為革蘭氏陰性菌或革蘭氏陽性菌。The hunger strike was started at 5 pm the day before the dissection, and the dissection was performed one night after the hunger strike. Anesthetized with ether, blood was collected from the heart, and intestinal lymph nodes (MLN) and liver were removed under aseptic conditions. After measuring the weight of the organs, the homogenized solution of the organs was cultured in a BL ocean containing 5% defibrin blood. The vegetable medium was cultured at 37 ° C for 72 hours under aerobic and anaerobic conditions, and the number of bacteria was counted. Gram staining was performed and the bacteria detected were either Gram-negative or Gram-positive.

其次，測量小腸的全長、盲腸與大腸的重量、盲腸的pH值。Second, measure the full length of the small intestine, the weight of the cecum and large intestine, and the pH of the cecum.

以自動血球分析儀(Sysmex ST-1800i)分析血液一般檢查。在血液一般檢查中，調查各種病態變化的指標。已知嗜中性球或單核球的增加是引起感染症(細菌)的原因。An automatic blood cell analyzer (Sysmex ST-1800i) was used to analyze the general blood tests. In general blood tests, various indicators of pathological changes are investigated. An increase in neutrophils or monocytes is known to cause infections (bacteria).

結果1Result 1

雖透過引朵美酒辛(indomethacin)誘導之小腸損害使腸道膜通透性亢進，但與對照群相比，營養組成物攝取群顯示顯著地抑制腸道通透性的亢進(第4圖)。由以上結果可知，藉由攝取營養組成物來抑制因引朵美酒辛(indomethacin)所造成的小腸損害。Although intestinal membrane permeability was enhanced by intestinal damage induced by indomethacin, compared with the control group, the nutrient composition ingestion group significantly inhibited the intestinal permeability increase (Figure 4) . From the above results, it was found that the intestinal damage caused by indomethacin was suppressed by ingesting a nutritional composition.

由此結果推測，攝取營養組成物具有預防因非固醇類抗炎症藥等所引起的小腸損害的可能性。From this result, it is speculated that ingestion of a nutritional composition has the possibility of preventing damage to the small intestine caused by non-steroidal anti-inflammatory drugs and the like.

結果2Result 2

因引朵美酒辛(indomethacin)誘導之小腸損害而對腸道黏膜防禦力的破壞、免疫力的降低等，使得原本消化道中的腸道細菌穿過腸道黏膜上皮阻障(barrier)，移行至肝臟或腸道膜淋巴結。Due to the intestinal damage induced by indomethacin, damage to the intestinal mucosa's defense force and decreased immunity, etc., caused the intestinal bacteria in the original digestive tract to pass through the intestinal mucosal barrier and migrate Liver or intestinal lymph nodes.

在投予引朵美酒辛(indomethacin)後的第4天與第8天，取出全部的腸道膜淋巴結與部分的肝臟，經均質化的溶液中的菌數經培養法測定。本實驗結果顯示，在投予引朵美酒辛(indomethacin)後第4天未於腸道膜淋巴結檢出細菌的個體，在一般流體食物群的9隻中有2隻，營養組成物群的10隻中有3隻。所有個體的肝臟中皆檢出細菌。在第8天未於腸道膜淋巴結檢出細菌的個體，在一般流體食物群的8隻中有1隻，營養組成物群的8隻中有4隻。一般流體食物群、營養組成物群的肝臟皆未檢出細菌。實際上各臟器中所檢出的菌數結果如第5圖所示。在投予引朵美酒辛(indomethacin)後第4天腸道膜淋巴結中所檢出的菌數，在營養組成物群與一般流體食物群中沒有顯著差異(未圖示)。另一方面，在營養組成物群之肝臟顯示較少的傾向(p=0.068)(第5圖上方)。在投予引朵美酒辛(indomethacin)後第8天，雖然對肝臟無細菌移位(BT)產生，但與一般流體食物群相比，營養組成物群中對腸道膜淋巴結的BT具有顯著的抑制效果(p<0.05)(第5圖下方)。On the 4th and 8th days after the administration of indomethacin, all the intestinal membrane lymph nodes and part of the liver were taken out, and the number of bacteria in the homogenized solution was measured by the culture method. The results of this experiment show that in individuals with no bacteria detected in the intestinal membrane lymph nodes on the 4th day after administration of indomethacin, 2 of the 9 fluid food groups and 10 of the nutrient composition group There are only 3 of them. Bacteria were detected in the liver of all individuals. On the 8th day, individuals with no bacteria detected in the intestinal membrane lymph nodes included 1 in 8 of the general fluid food group and 4 of 8 nutritional composition groups. No bacteria were detected in the liver of the general fluid food group and the nutrient composition group. Actually, the number of bacteria detected in each organ is shown in Fig. 5. The number of bacteria detected in the intestinal membrane lymph nodes on the 4th day after the administration of indomethacin was not significantly different between the nutrient composition group and the general fluid food group (not shown). On the other hand, the liver in the nutrient composition group showed less tendency (p = 0.068) (upper graph 5). On the eighth day after indomethacin administration, although no bacterial shift (BT) occurred in the liver, compared with the general fluid food group, the nutritional composition group had significant BT on intestinal lymph nodes. Inhibitory effect (p <0.05) (below Figure 5).

所檢出的細菌為好氧性革蘭氏陽性菌。The bacteria detected were aerobic Gram-positive bacteria.

由以上結果可知，攝取營養組成物抑制對腸道膜淋巴結或肝臟的BT。也就是說，藉由攝取營養組成物抑制因投予引朵美酒辛(indomethacin)造成之小腸損害所誘發的BT。推測攝取營養組成物可保護小腸，預防因非固醇類抗發炎藥等所引起的小腸損害的可能性。From the above results, it can be seen that ingestion of the nutritional composition inhibits BT to the intestinal membrane lymph nodes or the liver. That is, BT induced by damage to the small intestine caused by the administration of indomethacin is suppressed by ingesting a nutritional composition. It is speculated that ingestion of a nutritional composition may protect the small intestine and prevent the possibility of damage to the small intestine caused by nonsteroidal anti-inflammatory drugs and the like.

結果3Result 3

進行血液一般檢查，分析引朵美酒辛(indomethacin)投予前與投予後的變化。在血液一般檢查中，使用分析各種病態變化的指標。已知嗜中性球和單核球的增加是引起感染症(細菌)的原因。A general blood test was performed to analyze changes before and after administration of indomethacin. In general blood tests, indicators that analyze various pathological changes are used. The increase in neutrophils and monocytes is known to cause infections (bacteria).

檢查的結果顯示，在正常個體中，營養組成物群與一般流體食物群之間無顯著差異。另一方面，引朵美酒辛(indomethacin)投予組，與正常個體相比，白血球數上升(第6圖)。白血球的增加是因為淋巴球、嗜中性球、單核球的數目增加(第6圖)。在一般流體食物群中發現，白血球於第4天增加，並於第7天持續增加。另一方面，營養組成物群的白血球增加在第4天顯示高峰，之後減少。在白血球之中，各群組間被認為有差異者，尤其為嗜中性球與單核球的數目。雖然在第4天時各群組間沒有差異，但在第7天，與一般流體食物群相比，營養組成物群的嗜中性球與單核球的數目顯示低值。The results of the examination showed that in normal individuals, there was no significant difference between the nutritional composition group and the general fluid food group. On the other hand, the number of white blood cells increased in the indomethacin-administered group compared with normal individuals (Figure 6). The increase in white blood cells was due to an increase in the number of lymphocytes, neutrophils, and monocytes (Figure 6). It was found in the general fluid food group that white blood cells increased on the 4th day and continued to increase on the 7th day. On the other hand, the white blood cell increase of the nutritional composition group showed a peak on the fourth day, and then decreased. Among the white blood cells, those that are considered to be different between the groups, especially the number of neutrophils and mononuclear cells. Although there was no difference between the groups on the fourth day, the number of neutrophils and mononuclear spheres of the nutrient composition group showed a low value compared with the general fluid food group on the seventh day.

由以上結果判斷，因非固醇類抗發炎藥引起之小腸損害所誘發的細菌移位在營養組成物群中受到抑制的結果，使嗜中性球與單核球數目的上升受到抑制。Judging from the above results, the bacterial shift induced by small intestinal damage caused by non-steroidal anti-inflammatory drugs was inhibited in the nutritional composition group, and the increase in the number of neutrophils and monocytes was suppressed.

[實施例5][Example 5] 去除營養組成物中乳清蛋白水解物、異麥芽酮糖、源自醱酵乳之蛋白質的情形之變化1Changes in the case of removing whey protein hydrolysate, isomaltulose, and protein derived from fermented milk in nutritional composition 1

使用購自日本SLC(株)的C57BL/6小鼠(6週大，雄)。購買的動物在經1個星期的馴化後的體重為指標，分成5群。C57BL / 6 mice (6 weeks old, male) purchased from Japan SLC Co., Ltd. were used. The weight of the purchased animals after domestication for 1 week was used as an index and divided into 5 groups.

群組：Group:

第1群：一般流體食物(明治乳業：Meibalance)Group 1: General fluid food (Meiji Dairy: Meibalance)

第2群：營養組成物(明治乳業：MEIN)Group 2: Nutritional composition (Meiji Dairy: MEIN)

第3群：營養組成物-乳清蛋白水解物(營養組成物-P)Group 3: Nutritional Composition-Whey Protein Hydrolysate (Nutrition Composition-P)

(去除營養組成物中的乳清蛋白水解物)(Removal of whey protein hydrolysate from nutritional composition)

第4群：營養組成物-乳清蛋白水解物-異麥芽酮糖(營養組成物-P-I)Group 4: Nutrition Composition-Whey Protein Hydrolysate-Isomaltulose (Nutrition Composition-P-I)

(去除營養組成物中的乳清蛋白水解物與異麥芽酮糖)(Removes whey protein hydrolysate and isomaltulose from nutritional composition)

第5群：營養組成物-乳清蛋白水解物-異麥芽酮糖-夸克(Quark)(營養組成物-P-I-Q)Group 5: Nutrition composition-Whey protein hydrolysate-Isomaltulose-Quark (Nutrition composition-P-I-Q)

(去除營養組成物中的乳清蛋白水解物、異麥芽酮糖、夸克(Quark))(Remove whey protein hydrolysate, isomaltulose, Quark in nutrition composition)

將上述5個群組飼養2週。營養組成物中的夸克(Quark)與乳清蛋白水解物以酪蛋白代替，異麥芽酮糖以糊精代替。The above 5 groups were reared for 2 weeks. Quark and whey protein hydrolysate in the nutritional composition were replaced with casein, and isomaltulose was replaced with dextrin.

將12mg/kg的ConA(Sigma)由尾靜脈投予，隔日，***麻醉，由腹部大靜脈採血後，摘取肝臟、脾臟、盲腸、小腸。小腸為測量中央10cm的重量。12 mg / kg of ConA (Sigma) was administered through the tail vein. The next day, anesthesia with ether was performed. Blood was collected from the large abdominal vein, and then the liver, spleen, cecum, and small intestine were removed. The small intestine measures the weight of the center 10 cm.

體重與臟器重量的結果如第7圖、表14(投予ConA 24小時後的體重與每單位體重的臟器重量)所示。The results of body weight and organ weight are shown in Fig. 7 and Table 14 (body weight 24 hours after administration of ConA and organ weight per unit body weight).

體重、每單位體重的肝臟、脾臟重量在各群組間無顯著差異。與一般流體食物群相比，營養組成物群的盲腸重量顯著地增加。與營養組成物群相比，在去除營養組成物中的乳清蛋白水解物、異麥芽酮糖、夸克(Quark)的群，盲腸重量顯示明顯的低值，因此顯示這3個原料與盲腸的醱酵有關。與一般流體食物群相比，營養組成物群的小腸重量顯示顯著的高值。與營養組成物群相比，去除營養組成物中的乳清蛋白水解物、異麥芽酮糖、夸克(Quark)的群，小腸重量顯示顯著的低值，因此顯示這3個原料與小腸損害或發炎相關的可能性。Body weight, liver and spleen weight per unit weight did not differ significantly between groups. The weight of the cecum of the nutritional composition group is significantly increased compared to the general fluid food group. Compared with the nutritional composition group, the cecum weight showed a significantly lower value in the group that removed whey protein hydrolysate, isomaltulose, and Quark in the nutritional composition. Related to leaven. The small intestine weight of the nutritional composition group shows a significantly high value compared with a general fluid food group. Compared with the nutrient composition group, the group that removes whey protein hydrolysate, isomaltulose, and Quark in the nutrient composition shows a significantly lower value of the small intestine weight, and therefore shows that these three ingredients and small intestine damage Or inflammation-related possibilities.

乳清蛋白水解物、異麥芽酮糖、夸克(Quark)此3種成分可能與營養組成物之腸道保護作用或抗發炎作用有關。Whey protein hydrolysate, isomaltulose, and Quark may be related to the intestinal protective effect or anti-inflammatory effect of nutritional composition.

[實施例6][Example 6] 去除營養組成物中乳清蛋白水解物、異麥芽酮糖、源自醱酵乳之蛋白質的情形之變化2Changes in the case of removing whey protein hydrolysate, isomaltulose, and protein derived from fermented milk in nutritional composition 2

使用購自日本SLC(株)的C57BL/6小鼠(6週大，雄)。購買的動物在經1個星期的馴化後的體重為指標，分成6群。C57BL / 6 mice (6 weeks old, male) purchased from Japan SLC Co., Ltd. were used. The body weight of the purchased animals after one week of domestication was used as an index and divided into 6 groups.

群組(一般流體食物、營養組成物與實施例6相同)：Group (general fluid food and nutrition composition are the same as in Example 6):

第1群：一般流體食物Group 1: General fluid food

第2群：營養組成物Group 2: Nutritional composition

第3群：營養組成物-乳清蛋白水解物(-P)Group 3: Nutritional Composition-Whey Protein Hydrolysate (-P)

第4群：營養組成物-異麥芽酮糖(-I)Group 4: Nutritional Composition-Isomaltulose (-I)

(去除營養組成物中的異麥芽酮糖)(Removes isomaltulose from nutritional composition)

第5群：營養組成物-夸克(Quark)(-Q)Group 5: Nutrition Composition-Quark (-Q)

(去除營養組成物中的夸克(Quark))(Remove Quark in nutrition composition)

第6群：營養組成物-乳清蛋白水解物-異麥芽酮糖-夸克(Quark)(-P-I-Q)Group 6: Nutrition Composition-Whey Protein Hydrolysate-Isomaltulose-Quark (-P-I-Q)

將上述6個群組飼養2週。營養組成物中的蛋白質源夸克(Quark)與乳清蛋白水解物以酪蛋白代替，異麥芽酮糖以糊精代替而調製。The above 6 groups were reared for 2 weeks. The protein source Quark and whey protein hydrolysate in the nutritional composition are replaced with casein, and isomaltulose is prepared by replacing with dextrin.

將12mg/kg的ConA(Sigma)由尾靜脈投予，投予後2、4、8小時後由尾靜脈採血，隔日，***麻醉，由腹部大靜脈採血後，摘取肝臟、脾臟、盲腸、小腸、大腸。血漿中的ALT、AST以富士DRI-CHEM進行檢測。12 mg / kg of ConA (Sigma) was administered from the tail vein, and blood was collected from the tail vein at 2, 4, and 8 hours after the administration. The next day, anesthesia was performed with ether, and blood was collected from the large abdominal vein. Then the liver, spleen, cecum, and small intestine were removed. ,the large intestine. ALT and AST in plasma were detected by Fuji DRI-CHEM.

結果1Result 1

最終日體重及臟器重量的結果如表15所示。The results of the final daily weight and organ weight are shown in Table 15.

在各群組之間，體重與每單位體重的臟器重量(肝臟、脾臟)無顯著差異。與一般流體食物群相比，營養組成物群、第3群(-乳清蛋白水解物)、第4群(-異麥芽酮糖)的小腸、盲腸重量顯示顯著的高值。There was no significant difference between body weight and organ weight (liver, spleen) per unit body weight. The weight of the small intestine and cecum of the nutritional composition group, the third group (-whey protein hydrolysate), and the fourth group (-isomaltulose) showed significantly higher values than the general fluid food group.

結果2Result 2

投予ConA 24小時後的AST、ALT結果如第8圖所示。與營養組成物群相比，僅去除乳清蛋白水解物之群(第3群)與僅去除夸克(Quark)之群(第5群)的AST、ALT上升。僅去除異麥芽酮糖之(第4群)的AST、ALT值與營養組成物群大體上相同程度。與營養組成物群相比，去除營養組成物中的乳清蛋白水解物與異麥芽酮糖、夸克(Quark)的情形(第6群)，ALT值顯示顯著的高值，表示肝炎抑制作用主要與乳清蛋白水解物及夸克(Quark)有關。The results of AST and ALT 24 hours after administration of ConA are shown in Fig. 8. Compared with the nutrient composition group, the AST and ALT of the group which removed only the whey protein hydrolysate (group 3) and the group which removed only Quark (group 5) increased. The AST and ALT values of only the isomaltulose (Group 4) were almost the same as those of the nutrient composition group. Compared with the nutrient composition group, when the whey protein hydrolysate, isomaltulose, and Quark were removed from the nutrient composition group (Group 6), the ALT value showed a significantly higher value, indicating a hepatitis inhibitory effect. Mainly related to whey protein hydrolysate and Quark.

營養組成物的抗發炎作用判斷以乳清蛋白水解物與夸克(Quark)為主要成份。營養組成物的腸道功能維持及腸道保護作用與含有乳清蛋白水解物與異麥芽酮糖、脫脂凝乳的3種原料有關，雖然夸克(Quark)為主要成分夸克(Quark)。The anti-inflammatory effect of the nutritional composition is judged mainly on whey protein hydrolysate and quark. The intestinal function maintenance and intestinal protective effect of the nutritional composition are related to three kinds of raw materials including whey protein hydrolysate, isomaltulose, and skim curd, although Quark is the main ingredient Quark.

[比較例1]乳清蛋白水解物的製備[Comparative Example 1] Preparation of whey protein hydrolysate

將蛋白質含量為90%的乳清蛋白分離物之乾燥物(WPI、Davisco公司)以8%(w/v)蛋白質含量溶於蒸餾水。此溶液以85℃加熱2分鐘進行加熱處，使蛋白質變性。此加熱後的溶液pH為約7.5。水解為添加鹼性蛋白酶2.4L(酵素，Novozymes公司)至相對基質2.0%的濃度，於55℃反應3小時。接著，添加豬胰蛋白酶PTN 6.0S(Novozymes Japan)至相對基質3.0%的濃度，於55℃反應3小時。整個水解時間為6小時。反應結束時的pH為約7.0。乳清蛋白水解物在經離心處理(20,000×g、10分)後，以分級分子量10,000的UF膜進行處理(Millipore公司之Ultrafree-MC)。The dried whey protein isolate (WPI, Davisco) with a protein content of 90% was dissolved in distilled water at 8% (w / v) protein content. This solution was heated at 85 ° C for 2 minutes for heating to denature the protein. The pH of this heated solution was about 7.5. It was hydrolyzed by adding alkaline protease 2.4L (enzyme, Novozymes) to a concentration of 2.0% relative to the substrate and reacted at 55 ° C for 3 hours. Next, pig trypsin PTN 6.0S (Novozymes Japan) was added to a concentration of 3.0% relative to the substrate, and the reaction was performed at 55 ° C for 3 hours. The total hydrolysis time was 6 hours. The pH at the end of the reaction was about 7.0. The whey protein hydrolysate was subjected to centrifugation (20,000 × g, 10 minutes), and then treated with a UF membrane with a molecular weight of 10,000 (Ultrafree-MC from Millipore).

提供逆相HPLC滲透液(Permeate)。A reverse phase HPLC permeate was provided.

條件condition

試料：乳清蛋白水解物之UF滲透液(Permeate)Sample: UF permeate of whey protein hydrolysate

管柱：C18 SG120(資生堂社)4.6 mmφ×250 mmColumn: C18 SG120 (Shiseido) 4.6 mmφ × 250 mm

洗提液：A；0.1%的三氟乙酸水溶液/乙腈5/95Eluent: A; 0.1% trifluoroacetic acid aqueous solution / acetonitrile 5/95

B；0.1%的三氟乙酸水溶液/乙腈32/68 B; 0.1% trifluoroacetic acid aqueous solution / acetonitrile 32/68

A→B 60分鐘的線性濃度梯度A → B 60-minute linear concentration gradient

流速：1 mL/minFlow rate: 1 mL / min

檢測：215 nm(紫外/可見光偵測器)Detection: 215 nm (ultraviolet / visible light detector)

【產業利用性】[Industrial availability]

本發明組成物顯示促進小腸絨毛增生以及增加肌肉層厚度等的腸道功能亢進。因此，有效於腸道功能降低的高齡者或癌症患者等因投予抗生素或抗癌藥物所致腸道損害患者及術後或ICU等無法長時間補充營養所致的腸道功能低下之患者的腸道機能改善。對於健康人，也有效用於小腸絨毛生長而改善腸道功能。The composition of the present invention shows hyperintestinal function that promotes intestinal villus proliferation and increases muscle layer thickness. Therefore, it is effective for elderly patients with reduced intestinal function, cancer patients, etc. Patients with intestinal damage caused by administration of antibiotics or anticancer drugs, and patients with intestinal dysfunction caused by postoperative or ICU that cannot provide nutrition for a long time. Improved bowel function. For healthy people, it is also effective for small intestinal villi growth to improve intestinal function.

本發明之組成物有效於小腸的組織損害預防。本發明之組成物更顯示抗發炎作用，亦可作為抗炎症藥劑使用。The composition of the present invention is effective for preventing tissue damage of the small intestine. The composition of the present invention further exhibits an anti-inflammatory effect, and can also be used as an anti-inflammatory agent.

第1圖為小腸面積之比較圖。Figure 1 is a comparison chart of the area of the small intestine.

第2圖為小腸病理組織相片(蘇木精-尹紅染色)。Figure 2 is a photograph of the small intestine pathology (hematoxylin-yin red staining).

第3圖為正常小腸組織相片(H‧E染色×150倍)。Figure 3 is a photograph of normal small intestine tissue (H‧E staining × 150 times).

第4圖顯示PSP尿中***率。平均值±SE、Student’s t檢定(第0天：n=9，第2天：n=9～10，第4天：n=9～10，第8天：n=8)。Figure 4 shows the urine excretion rate of PSP. Mean ± SE, Student's t test (Day 0: n = 9, Day 2: n = 9-10, Day 4: n = 9-10, Day 8: n = 8).

第5圖顯示投予引朵美酒辛(indomethacin)後，由肝臟(上圖)及腸道淋巴結(下圖)中所檢出的細菌數。平均值±SE、Student’s t檢定；*:p<0.05(第0天：n=6，第4天：n=8～9，第8天：n=8)。Figure 5 shows the number of bacteria detected in the liver (upper panel) and intestinal lymph nodes (lower panel) after administration of indomethacin. Mean ± SE, Student's t test; *: p <0.05 (Day 0: n = 6, Day 4: n = 8-9, Day 8: n = 8).

第6圖顯示投予引朵美酒辛(indomethacin)後，血液中嗜中性球與單核球數目的變化。平均值±SD、Student’s t檢定；*:p<0.05(第8天：n=7～8)。Figure 6 shows the change in the number of neutrophils and mononuclear spheres in the blood after administration of indomethacin. Mean ± SD, Student's t test; *: p <0.05 (day 8: n = 7 to 8).

第7圖顯示投予刀豆蛋白A(ConA)24小時後的小腸重量(上圖)與盲腸重量(下圖)。平均值±SD、Scheffe檢定；*:p<0.05(n=8～10)。SF：一般流體食物，ND：營養組成物，-P：營養組成物-乳清蛋白水解物，-P-I：營養組成物-乳清蛋白水解物-異麥芽酮糖，-P-I-Q：營養組成物-乳清蛋白水解物-異麥芽酮糖-夸克(Quark)。Figure 7 shows the weight of the small intestine (top) and the weight of the cecum (bottom) 24 hours after administration of concanavalin A (ConA). Mean ± SD, Scheffe test; *: p <0.05 (n = 8 ～ 10). SF: general fluid food, ND: nutritional composition, -P: nutritional composition-whey protein hydrolysate, -PI: nutritional composition-whey protein hydrolysate-isomaltulose, -PIQ: nutritional composition -Whey protein hydrolysate-Isomaltulose-Quark.

第8圖顯示投予刀豆蛋白A(ConA)後8小時血漿中的AST、ALT活性。平均值±SD、Mann-Whitney檢定；*:p<0.05(n=5～9)。Figure 8 shows AST and ALT activities in plasma 8 hours after administration of Concanavalin A (ConA). Mean ± SD, Mann-Whitney test; *: p <0.05 (n = 5-9).

Claims

一種促進小腸絨毛生長、使小腸肌肉層厚度增加、改善腸道功能或預防小腸組織損害之組成物，其係藉由調和含有作為蛋白質之乳蛋白質之水解物及源自醱酵乳之蛋白質、作為脂質之油脂以及作為糖類之異麥芽酮糖的組成物與高溫殺菌後進行均質化之步驟被製造，其中乳蛋白質為將乳清膜分離或離子交換樹脂處理或電透析處理後，濃縮或濃縮及乾燥所獲得之乳清蛋白分離物(WPI)，或為將乳清經膜分離後，濃縮或濃縮及乾燥所獲得之乳清蛋白濃縮物(WPC)，而乳蛋白質之水解物為以下(a)、(b)、(c)或(d)中所記載之乳清蛋白水解物：(a)藉由將乳清蛋白分離物(WPI)或乳清蛋白濃縮物(WPC)以蛋白酶水解、將此水解物以具有截留值10,000以上之超過濾(Ultrafiltration：UF)裝置處理，針對含有此水解物之過濾物將該蛋白酶去活化而獲得的乳清蛋白水解物；(b)藉由將加熱變性的乳清蛋白分離物(WPI)以內切胜肽酶及外切胜肽酶水解後，以離子交換樹脂將此水解物中的芳香族胺基酸吸附處理而獲得的乳清蛋白水解物；(c)將蛋白質含量為至少65%乳清蛋白濃縮物(WPC)的12%水溶液，在超過60℃的熱處理後，以來自地衣芽孢桿菌(B.licheniformis)之Alcalase(登錄商標)及來自枯草桿菌(B.subtilis)之Neutrase(登錄商標)水解至DH為15~35%，將此水解物進行具有超過10,000之截留值的超過濾(Ultrafiltration：UF)後，以奈過濾(Nanofiltration：NF)進行濃縮，將此NF濃縮液經噴霧乾燥後，所獲得無臭，苦味少的乳清蛋白水解物；(d)藉由將以8%之蛋白質含量來含有乳清蛋白分離物(WPI)的溶液以85℃加熱而獲得pH為約7.5的溶液，將此溶液以蛋白酶水解而獲得pH為約7.0的水解物，針對此水解物進行分級分子量10,000的超過濾膜處理，將所獲得之滲透液(Permeate)提供於逆相HPLC而獲得的乳清蛋白水解物。 A composition that promotes the growth of small intestine villi, increases the thickness of the small intestine muscle layer, improves intestinal function, or prevents damage to small intestine tissue. The fats and oils and the composition of isomaltulose, which is a sugar, are manufactured by homogenization after high-temperature sterilization. The milk protein is concentrated or concentrated after whey membrane separation or ion exchange resin treatment or electrodialysis treatment. The whey protein isolate (WPI) obtained after drying, or the whey protein concentrate (WPC) obtained after the whey is separated through a membrane, is concentrated or concentrated and dried, and the hydrolysate of milk protein is the following (a ), (B), (c) or (d): (a) by hydrolyzing whey protein isolate (WPI) or whey protein concentrate (WPC) with a protease, This hydrolysate is treated with an ultrafiltration (UF) device having a cut-off value of 10,000 or more, and a whey protein hydrolysate obtained by deactivating the protease with respect to the filtrate containing the hydrolysate; (b) by heating transsexual Whey protein isolate (WPI) is a whey protein hydrolysate obtained by hydrolyzing endo-peptidase and exo-peptidase, and using an ion exchange resin to adsorb and treat the aromatic amino acid in the hydrolysate; (c ) A 12% aqueous solution with a protein content of at least 65% whey protein concentrate (WPC), after a heat treatment in excess of 60 ° C., with Alcalase (registered trademark) from B. licheniformis and from Bacillus subtilis ( Neutrase (registered trademark) of B.subtilis) was hydrolyzed to a DH of 15 to 35%, and the hydrolysate was subjected to a cut-off value exceeding 10,000. After ultrafiltration (UF), the solution was concentrated by nanofiltration (NF), and the NF concentrated solution was spray-dried to obtain a whey protein hydrolysate that was odorless and less bitter; (d) A solution containing whey protein isolate (WPI) with a protein content of 8% was heated at 85 ° C to obtain a solution having a pH of about 7.5. This solution was hydrolyzed by a protease to obtain a hydrolysate having a pH of about 7.0. The product was subjected to ultrafiltration membrane treatment with a fractional molecular weight of 10,000, and the obtained permeate was supplied to a whey protein hydrolysate obtained by reverse-phase HPLC.

一種如申請專利範圍第1項所述之組成物的製造方法，包括：調和含有作為蛋白質之申請專利範圍第1項中所記載的乳蛋白質之水解物及源自醱酵乳之蛋白質、作為脂質之油脂以及作為糖類之異麥芽酮糖的組成物的步驟、將調和物進行高溫殺菌的步驟，以及將高溫殺菌後之調和物進行均質化的步驟。 A method for producing a composition according to item 1 of the scope of patent application, comprising: reconciling a hydrolysate containing milk protein described in item 1 of the scope of patent application as a protein, a protein derived from fermented milk, and a lipid A step of oil and fat and a composition of isomaltulose which is a sugar, a step of sterilizing the blend at high temperature, and a step of homogenizing the blend after sterilization at high temperature.

一種作為蛋白質之乳蛋白質之水解物及源自醱酵乳之蛋白質、作為脂質之油脂以及作為糖類之異麥芽酮糖用於製造如申請專利範圍第1項所述之促進小腸絨毛生長之組成物的用途。 A hydrolysate of milk protein as protein and protein derived from fermented milk, fats and oils as lipid, and isomaltulose as sugar for producing a composition for promoting intestinal villi growth as described in item 1 of the scope of patent application the use of.

如申請專利範圍第3項所述之用途，其中該源自醱酵乳之蛋白質係來自於新鮮乳酪。 The use as described in claim 3, wherein the protein derived from fermented milk is derived from fresh cheese.

一種作為蛋白質之乳蛋白質之水解物及源自醱酵乳之蛋白質、作為脂質之油脂以及作為糖類之異麥芽酮糖用於製造如申請專利範圍第1項所述之使小腸肌肉層厚度增加之組成物的用途。 A hydrolysate of milk protein as protein and protein derived from fermented milk, fats and oils as lipid, and isomaltulose as sugar Use for manufacturing a composition for increasing the thickness of the small intestinal muscle layer as described in item 1 of the scope of patent application.

如申請專利範圍第5項所述之用途，其中該源自醱酵乳之蛋白質係來自於新鮮乳酪。 The use as described in claim 5 of the application, wherein the protein derived from fermented milk is derived from fresh cheese.

一種作為蛋白質之乳蛋白質之水解物及源自醱酵乳之蛋白質、作為脂質之油脂以及作為糖類之異麥芽酮糖用於製造如申請專利範圍第1項所述之改善腸道功能之組成物的用途。 A hydrolysate of milk protein as protein and protein derived from fermented milk, oils and fats as lipid, and isomaltulose as sugar for producing a composition for improving intestinal function as described in item 1 of the scope of patent application the use of.

如申請專利範圍第7項所述之用途，其中該源自醱酵乳之蛋白質係來自於新鮮乳酪。 The use as described in claim 7 of the application, wherein the protein derived from fermented milk is derived from fresh cheese.

一種作為蛋白質之乳蛋白質之水解物及源自醱酵乳之蛋白質、作為脂質之油脂以及作為糖類之異麥芽酮糖用於製造如申請專利範圍第1項所述之預防小腸組織損害之組成物的用途。 A hydrolysate of milk protein as protein and protein derived from fermented milk, oils and fats as lipid, and isomaltulose as sugar for producing a composition for preventing small intestinal tissue damage as described in item 1 of the scope of patent application the use of.

如申請專利範圍第9項所述之用途，其中該源自醱酵乳之蛋白質係來自於新鮮乳酪。 The use according to item 9 of the patent application scope, wherein the protein derived from fermented milk is derived from fresh cheese.

一種作為蛋白質之申請專利範圍第1項中所記載之乳蛋白質之水解物及源自醱酵乳之蛋白質以及作為糖類之異麥芽酮糖用於製造改善腸道功能之被高溫殺菌後均質化之組成物的用途。 A protein hydrolysate of milk protein and a protein derived from fermented milk as described in item 1 of the scope of application for protein as a protein, and isomaltulose, which is a sugar, is used for the manufacture of homogenized after high temperature sterilization to improve intestinal function Use of the composition.

如申請專利範圍第11項所述之用途，其中該源自醱酵乳之蛋白質係來自於新鮮乳酪。 The use according to item 11 of the patent application scope, wherein the protein derived from fermented milk is derived from fresh cheese.

一種作為蛋白質之申請專利範圍第1項中所記載之乳蛋白質之水解物及源自醱酵乳之蛋白質以及作為糖類之異麥芽酮糖用於製造預防小腸組織損害之被高溫殺菌後均質化之組成物的用途。 A hydrolysate of milk protein, a protein derived from fermented milk, and a carbohydrate as described in item 1 of the scope of application for protein as a protein Isomaltulose is used to produce a composition that is homogenized after high temperature sterilization to prevent damage to small intestine tissue.

如申請專利範圍第13項所述之用途，其中該源自醱酵乳之蛋白質係來自於新鮮乳酪。 The use according to item 13 of the application, wherein the protein derived from fermented milk is derived from fresh cheese.