TWI472300B - 包含核苷酸及/或類胡蘿蔔素之低卡路里嬰兒配方於降低後續生命中不利健康效應之用途 - Google Patents
包含核苷酸及/或類胡蘿蔔素之低卡路里嬰兒配方於降低後續生命中不利健康效應之用途 Download PDFInfo
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- A—HUMAN NECESSITIES
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Description
本發明係有關包括核苷酸及/或類胡蘿蔔素之低卡路里嬰兒配方於減低後續生命中長期不利健康效應(包括肥胖)之用途。亦揭示包括核苷酸及/或類胡蘿蔔素之低卡路里、低蛋白質嬰兒配方,其用於降低後續生命中長期不利健康效應(包括肥胖)。
本申請案主張2011年12月27日申請之Marriage等人之美國臨時專利申請案第61/580,442號的優先權,該案以全文引用的方式併入本文中。
發炎性反應為身體在感染劑侵入、抗原攻擊或物理、化學或創傷損傷後對恢復及維持內穩定所作之嘗試。雖然發炎性反應通常視為對損傷所作出之有益健康的反應,但若免疫系統未得到適當調節,則其可呈現不合需要之生理學反應。具體而言,未經調解之氧化及相關發炎為早產兒及足月兒之組織損傷及臨床重大疾病之主要原因。此在很大程度上歸因於嬰兒及尤其早產兒之天然免疫系統功能未成熟。
發炎為全世界非傳染性疾病、尤其肥胖及其共同罹病之主要機制之一。舉例而言,肥胖之特徵為脂肪組織之慢性低度發炎,其會造成胰島素抗性、2型糖尿病(非胰島素依賴性糖尿病)及心血管疾病。咸信由先天免疫系統(亦即巨噬細胞)及脂肪組織(例如脂肪因子)之細胞分泌之細胞激素
為調節發炎性環境之關鍵。詳言之,IL-1β、TNF-α及NF-κB路徑之活化與肥胖之負面代謝效應(包括心血管疾病及2型糖尿病)有關。此外,對NF-κB路徑之若干獨立臂的抑制顯示極少體重增加、胰島素敏感性增加、血脂概況改善及發炎減少。
母乳哺育與嬰兒免疫系統之發育增強及平衡生長及成熟相關,從而提供嬰兒保護以防感染及發炎性相關疾病。母乳似乎含有抗氧化劑,諸如超氧化歧化酶、麩胱甘肽過氧化酶及觸酶;或其他非酶性抗氧化劑,諸如麩胱甘肽、乳鐵傳遞蛋白及多酚;除抗氧化劑外之物質,諸如維生素A、C、E及硒。
並非所有嬰兒均接受人類母乳。此外,目前無可用於預防發炎性相關疾病(諸如肥胖及胰島素抗性)之疫苗。因此,開發安全且有效之預防性或治療性方法將為有益的,尤其有益於嬰兒。詳言之,經設計為在組成及功能方面更接近母乳之嬰兒配方將向嬰兒提供益處。
因此,將需要提供一種可模擬母乳之抗氧化保護性效應的嬰兒配方。若該等配方可降低後續生命中發炎性相關疾病(諸如肥胖)之風險,則其更為有利。
本發明係有關營養配方及具體而言包括至少一種核苷酸及/或至少一種類胡蘿蔔素之低卡路里或低卡路里/低蛋白質嬰兒配方之用途,其用於降低後續生命中一些可能發炎性相關疾病及尤其後續生命中肥胖之風險。該等低卡路里
嬰兒配方中所包括之核苷酸及/或類胡蘿蔔素可調節對發炎性刺激之免疫反應,藉此減少發炎及其不利健康效應。本發明之低卡路里配方當在生命第一年期間投與嬰兒時進一步為嬰兒之生長及發育提供足夠營養。
因此,在一個實施例中,本發明係有關一種降低後續生命中肥胖之方法。該方法包含向有需要之嬰兒在生命第一年中投與嬰兒配方,其中該嬰兒配方之能量含量小於650Kcal/L且包含至少一種核苷酸。
在另一實施例中,本發明係有關一種降低後續生命中肥胖之方法。該方法包含向有需要之嬰兒在生命第一年中投與嬰兒配方,其中該嬰兒配方之能量含量小於650Kcal/L且包含至少一種類胡蘿蔔素。
在另一實施例中,本發明係有關一種降低後續生命中肥胖之方法。該方法包含向有需要之嬰兒在生命第一年中投與嬰兒配方,其中該嬰兒配方之能量含量小於650Kcal/L且包含至少一種核苷酸及至少一種類胡蘿蔔素。
在另一實施例中,本發明係有關一種用於降低後續生命中肥胖風險之嬰兒配方,其包含小於650Kcal/L之能量含量且包含至少一種核苷酸。
在另一實施例中,本發明係有關一種用於降低後續生命中肥胖風險之嬰兒配方,其包含小於650Kcal/L之能量含量且包含至少一種類胡蘿蔔素。
在另一實施例中,本發明係有關一種用於降低後續生命中肥胖風險之嬰兒配方,其包含小於650Kcal/L之能量含
量且包含至少一種核苷酸及至少一種類胡蘿蔔素。
現令人驚訝地發現足量之包括單獨核苷酸、單獨類胡蘿蔔素或核苷酸與類胡蘿蔔素之組合的低卡路里嬰兒配方可減少後續生命中發炎性相關疾病及尤其後續生命中肥胖。
亦發現包括單獨核苷酸、單獨類胡蘿蔔素或核苷酸與類胡蘿蔔素之組合的低卡路里嬰兒配方可降低後續生命中胰島素抗性、2型糖尿病(非胰島素依賴性糖尿病)、心血管疾病及動脈粥樣硬化之風險。詳言之,經由抗發炎性策略,使會損傷組織之慢性發炎減至最少,從而預防及/或延遲此等疾病在嬰兒後續生命中之發展。
本發明之低卡路里嬰兒配方包括至少一種核苷酸、至少一種類胡蘿蔔素或其組合。在本文中所揭示之一些實施例中可另外為低蛋白質嬰兒配方之低卡路里嬰兒配方提供嬰兒足量類胡蘿蔔素及/或核苷酸以提供有效且簡單的降低嬰兒後續生命中長期不利健康效應(包括例如肥胖及心血管疾病)之發生率的方法。
嬰兒配方為嬰兒之生長及成熟提供所需營養益處,同時提供嬰兒降低長期不利健康效應之發生率的其他顯著優點,該等長期不利健康效應中之許多繼續每天折磨愈來愈多的青少年及成年人。有利地向嬰兒提供如本文中所述之此等益處以及其他益處而無任何類型之膳食變化或特殊膳食需求。如本文中所述之嬰兒配方可提供嬰兒可靠的高品質營養,以及在早期生命中為嬰兒提供規劃以使得嬰兒具
有有益健康的體型之開端且改善後續生命中一般總體健康狀況。如本文中所述之嬰兒配方在早期生命中提供嬰兒營養益處,其使後續生命具有重要健康益處,從而使嬰兒作為青少年及成年人可能產生更長、更健康之生命。
下文詳細描述本發明之嬰兒配方及方法的此等及其他及視情況存在之特點以及許多其他視情況存在之變化及添加中之一些。
術語「殺菌釜」與「殺菌釜滅菌」在本文中可互換使用,且除非另外說明,否則係指用營養液(諸如液體嬰兒配方)填充容器、最通常為金屬罐或其他類似封裝,接著使填充液體之封裝經受必要熱滅菌步驟,以形成殺菌釜滅菌之營養液產品的習慣作法。
術語「無菌」與「無菌滅菌」可互換使用,且除非另外說明,否則係指不依賴上述殺菌釜封裝步驟製造封裝產品,其中在填充之前對營養液及封裝分開進行滅菌,接著在滅菌或無菌加工條件下組合以形成經滅菌、無菌封裝之營養液產品。
如本文中所使用,術語「營養配方」或「營養產品」或「營養組合物」可互換使用且除非另外說明,否則係指如此項技術中已知之營養液、營養粉、營養固體、營養半液體、半固體、營養補充劑、營養錠劑及任何其他營養食物產品。營養粉可復原形成營養液,其均包含脂肪、蛋白質及碳水化合物中之一或多者,且適合於人類經口服用。營養配方可包括嬰兒配方。
除非另外說明,否則如本文中所使用,術語「營養液」係指呈即食液體形式、濃縮形式之營養產品及在使用之前藉由復原本文中所述之營養粉所製成之營養液。
除非另外說明,否則如本文中所使用,術語「營養粉」係指呈可流動或可用勺舀取形式之營養產品,其可在服用之前用水或另一水性液體復原且包括噴霧乾燥粉末與乾式混合/乾式摻合粉末。
除非另外說明,否則如本文中所使用,術語「營養半固體」係指在性質(諸如剛性)上介於固體與液體中間之營養產品。一些半固體實例包括布丁、明膠及麵團。
除非另外說明,否則如本文中所使用,術語「營養半液體」係指在性質(諸如流動性質)上介於液體與固體中間之營養產品。一些半液體實例包括奶昔(thick shake)及液體凝膠。
除非另外說明,否則如本文中所使用,術語「嬰兒」係指12個月齡或更幼小之兒童。如本文中所使用,術語「早產兒」係指在妊娠36週之前出生之嬰兒。本文中所使用,術語「足月兒」係指在妊娠36週時或之後出生之嬰兒。
除非另外說明,否則如本文中所使用,術語「新生兒」係指小於約3個月齡之嬰兒,包括0至約2週齡之嬰兒。新生兒可為足月兒或早產兒。
除非另外說明,否則如本文中所使用,術語「嬰兒配方」係指適合於嬰兒服用之液體及固體營養產品。除非本文另外說明,否則術語「嬰兒配方」意欲涵蓋足月兒配方
與早產兒配方。
除非另外說明,否則如本文中所使用,術語「早產兒配方」係指適合於早產兒服用之液體及固體營養產品。
如本文中所使用,術語「全卡路里嬰兒配方」係指與嬰兒配方中照慣例所包括之熱量密度或能量含量相比,配方之熱量密度或能量含量未降低的嬰兒配方。通常,全卡路里嬰兒配方之能量含量將為至少650kcal/L,包括至少660kcal/L,且更通常為至少676kcal/L,包括650kcal/L至800kcal/L。
如本文中所使用,術語「低卡路里嬰兒配方」係指與全卡路里嬰兒配方相比,每體積具有更低能量含量之嬰兒配方。
如本文中所使用,術語「後續生命」係指自青少年期至成年期之生命時期。
如本文中所使用,術語「易患」及「處於風險中」可互換用於指對某種病狀或疾病之抵抗力極小之個體,包括在遺傳上易患該病狀或疾病、具有該病狀或疾病之家族史及/或具有該病狀或疾病之症狀。
除非另外說明,否則如本文中所使用,術語「發炎性疾病」、「發炎性相關疾病」或「發炎性病狀」係指特徵為發炎之任何疾病、病症或病狀。
除非另外說明,否則如本文中所使用之所有百分比、份數及比率均以總組合物之重量計。除非另外說明,否則所有該等重量在其與所列成份相關時係基於活性程度且因此
不包括市售物質中可包括之溶劑或副產物。
如本文中所使用之數值範圍意欲包括該範圍內之每一個數及數之子集,無論是否具體揭示。此外,此等數值範圍應解釋為對有關該範圍內之任何數及數之子集的主張提供支持。舉例而言,揭示1至10應解釋為支持2至8、3至7、5至6、1至9、3.6至4.6、3.5至9.9等範圍。
除非另外說明或所提及之內容明確暗示相反,否則本發明中所有對單數特徵或限制之提及均應包含相應的複數特徵或限制,且反之亦然。
除非另外說明或所提及之內容明確暗示相反,否則如本文中所使用之方法或製程步驟之所有組合可以任何次序進行。
本發明之嬰兒配方的各種實施例亦可實質上不含本文中所述之任何視情況選用或所選必需成份或特點,其限制條件為剩餘嬰兒配方仍有如本文中所述之所有所需成份或特點。在此上下文中,且除非另外說明,否則術語「實質上不含」意謂所選嬰兒配方含有小於功能量之視情況選用之成份,通常小於1重量%,包括小於0.5重量%,包括小於0.1重量%,且亦包括0重量%之該視情況選用或所選必需成份。
本發明之嬰兒配方及方法可包含如本文中所述之產品及方法的必需要素、由其組成或基本上由其組成,以及本文中所述或另外適用於營養嬰兒配方應用中之任何其他或視情況選用之要素。
本發明之嬰兒配方可以任何已知或另外適合之口服產品形式調配及投與。任何固體、液體、半固體、半液體或粉末形式(包括其組合或變化)適合用於本文,其限制條件為該等形式允許安全且有效地將亦如本文中所定義之必需成份經口傳遞至個體。
適合用於本文中所揭示之產品及方法的產品形式之特定非限制性實例包括例如液體及粉末早產兒配方、液體及粉末足月兒配方以、及液體及粉末基本及半基本配方。
本發明之嬰兒配方希望調配為膳食產品形式,其在本文中定義為包含呈含有脂肪、蛋白質及碳水化合物中之至少一者的產品形式之本發明之成份的實施例。
嬰兒配方可用足夠種類及量之養分來調配以提供唯一、主要或補充營養源,或提供用於罹患特定疾病或病狀之嬰兒或具有目標營養益處之特殊化營養產品。
本發明之嬰兒配方希望調配用於足月兒與早產兒。嬰兒配方希望調配用於餵養出生後最初數天、數週或數月之嬰兒,且包括用於餵養0至1歲、包括0至6個月、包括0至4個月及包括0至2個月之嬰兒。在一些實施例中,嬰兒配方用於在生命最初數週內,包括出生至生命4週,包括出生至生命3週,包括出生至生命2週,且包括出生至生命第1週餵養新生兒。應瞭解,本發明之嬰兒配方的投與並不限於僅在出生後最初6個月期間投與,而且亦可投與年齡較大的嬰兒。
營養液包括濃縮與即食營養液。此等營養液最通常調配為懸浮液、乳液、或透明或實質上透明的液體。
適合使用之營養乳液可為水性乳液,包含蛋白質、脂肪及碳水化合物。雖然此等乳液在約1℃至約25℃下通常為可流動或可飲用之液體且通常呈水包油、油包水或複合水性乳液形式,但該等乳液最通常為具有連續水相及不連續油相之水包油乳液形式。
營養液可為且通常為存放穩定的。營養液通常含有以營養液之重量計至多約95重量%水,包括約50%至約95%,亦包括約60%至約90%,且亦包括約70%至約85%水。雖然營養液可具有各種產品密度,但密度最通常為約1.01g/mL或更高,包括大於約1.02g/mL,包括大於約1.03g/mL,包括大於約1.04g/mL,包括大於約1.055g/mL,包括約1.06g/mL至約1.12g/mL,且亦包括約1.085g/mL至約1.10g/mL。
營養液之pH值範圍可為約3.5至約8,但通常最宜在約4.5至約7.5範圍內,包括約4.5至約7.0,包括約4.5至約6.5,包括約4.5至約6.0。在其他實施例中,pH值範圍可為約5.5至約7.3,包括約5.5至約7.0,包括約5.5至約6.5,包括約6.2至約7.2,包括約6.2至約7.0,且包括約6.2至約6.5。
儘管營養液之食用份量可視許多變數而變,但典型食用份量通常為至少約2mL、或甚至至少約5mL、或甚至至少
約10mL、或甚至至少約25mL,包括約2mL至約300mL之範圍,包括約100mL至約300mL、約4mL至約250mL、約150mL至約250mL、約10mL至約240mL、及約190mL至約240mL。
營養粉呈可流動或實質上可流動微粒組合物,或至少微粒組合物形式。尤其適合之營養粉形式包括噴霧乾燥、聚結或乾式摻合粉末組合物或其組合,或藉由其他適合方法製備之粉末。組合物可容易地用勺或類似的其他裝置舀取及量測,其中該等組合物可容易地用適合之水性液體(通常為水)復原,以形成諸如嬰兒配方之營養液,以供立即經口或經腸使用。在此上下文中,「立即」使用通常意謂在約48小時內,最通常在約24小時內,較佳在復原後立即或在復原20分鐘內。
相對於習知足月兒及早產兒配方,本發明之嬰兒配方具有減少之能量含量(在本文中與術語「熱量密度」互換使用)。嬰兒配方之減少能量密度與如本文中所述之包括類胡蘿蔔素及/或核苷酸之配方特定組份組合可有助於減少如下文所述之長期不利健康效應。在一些實施例中,減少之能量含量可藉由減少配方中一或多種多量養分(macro-nutrients)之含量達成。具體而言,本發明之嬰兒配方提供小於650kcal/L之熱量密度或能量含量,包括約200kcal/L至小於650kcal/L,包括約200kcal/L至約600kcal/L,且
更特別為約250kcal/L至約500kcal/L。在一些實施例,熱量密度可介於約250kcal/L與約450kcal/L之間,或甚至為約250kcal/L至約400kcal/L,或甚至為約250kcal/L至約300kcal/L。與本發明之嬰兒配方相比,習知足月兒及早產兒配方(在本文中亦稱為「全卡路里嬰兒配方」)之熱量密度或能量含量顯著較高,範圍通常為650kcal/L至880kcal/L。
當本發明之嬰兒配方呈粉末形式時,則意欲在使用之前復原粉末以獲得上述熱量密度及其他養分需求。同樣,當本發明之嬰兒配方呈濃縮液體形式時,則意欲在使用之前稀釋濃縮物以獲得所需熱量密度及養分需求。嬰兒配方亦可調配為已具有所需熱量密度及養分需求之即食液體。
根據本文中所述之方法,本發明之嬰兒配方希望投與嬰兒及尤其新生兒。該等方法可包括根據本文中所述之每日配方攝取體積餵以該嬰兒配方。
嬰兒配方之能量組份最通常由脂肪、蛋白質及碳水化合物養分之組合提供。在一些實施例,蛋白質可包含總卡路里之約4%至約40%,包括約10%至約30%,亦包括約15%至約25%;碳水化合物可包含小於總卡路里之50%,包括約5%至約45%,亦包括小於約42%,且亦包括約20%至約37%;且脂肪可包含配方卡路里之其餘部分,最通常小於卡路里之約60%,包括約30%至約60%。蛋白質、碳水化合物及脂肪之其他例示性量在下文陳述以用於替代性實施例中。
本發明之嬰兒配方可包含單獨一或多種核苷酸或一或多種核苷酸與如本文中所述之其他營養組份的組合,以減少個體之長期不利健康效應,包括長期肥胖。除非在特定實施例中另外說明,否則如本文中所使用,「核苷酸」包括核苷酸、核苷、核鹼基及其組合。適合之核苷酸可選自由核苷、嘌呤鹼基、嘧啶鹼基、核糖及去氧核糖組成之群。核苷酸可呈單磷酸酯、二磷酸酯或三磷酸酯形式。核苷酸可為核糖核苷酸或去氧核糖核苷酸。核苷酸可為單體、二聚體或多聚體(包括RNA及DNA)。核苷酸可以游離酸形式或以鹽(較佳為單鈉鹽)形式存在於嬰兒配方中。
用於營養組合物中之其他適合核苷酸及/或核苷包括3'-去氧腺苷、5'-單磷酸胞苷、5'-單磷酸尿苷、5'-單磷酸腺苷、5'-1-單磷酸鳥苷及/或5'-單磷酸腺苷中之一或多者,更佳為5'-單磷酸胞苷、5'-單磷酸尿苷、5'-單磷酸腺苷、5'-單磷酸鳥苷及5'-單磷酸腺苷。在一些實施例,核苷酸呈游離形式且包括腺嘌呤、胞嘧啶、尿嘧啶、鳥嘌呤及胸腺嘧啶。一些尤其較佳核苷酸包括5'單磷酸胞苷、5'單磷酸鳥苷二鈉、5'單磷酸尿苷二鈉及5'單磷酸腺苷。任何此等特定較佳核苷酸可單獨、組合使用。
核苷酸於嬰兒配方中之含量以核苷酸總量計為至少約10mg/L,包括約10mg/L至約200mg/L,包括約10mg/L至約150mg/L,包括約10mg/L至約125mg/L,包括約42mg/L至約102mg/L,且包括至少約72mg/L嬰兒配方。
在一個特定實施例中,當嬰兒配方為營養粉時,核苷酸之含量可為至少約0.007%,包括約0.0078%至約0.1556%,且包括約0.056%(以營養粉之重量計),或每100公克營養粉至少約0.007公克,包括約0.0078公克至約0.1556公克,且包括約0.056公克核苷酸。
在另一特定實施例中,當嬰兒配方為即食營養液時,核苷酸之含量為至少約0.001%,包括約0.001%至約0.0197%,且包括約0.0071%(以營養液之重量計),或每100公克即食營養液至少約0.001公克,包括約0.001公克至約0.0197公克,且包括約0.0071公克核苷酸。
在另一特定實施例中,當嬰兒配方為濃縮營養液時,核苷酸之含量為至少約0.0019%,包括約0.0019%至約0.0382%,且包括約0.0138%(以營養液之重量計),或每100公克濃縮營養液至少約0.0019公克,包括約0.0019公克至約0.0382公克,且包括約0.0138公克核苷酸。
本發明之嬰兒配方可包括單獨類胡蘿蔔素或類胡蘿蔔素與如本文中所述之其他營養組份(包括核苷酸)的組合,以減少個體之長期不利健康效應,包括長期肥胖。類胡蘿蔔素可包括一或多種類胡蘿蔔素,及尤其為類胡蘿蔔素葉黃素、番茄紅素、玉米黃素及/或β-胡蘿蔔素之組合。
通常較佳地,嬰兒配方包含葉黃素、番茄紅素、玉米黃素、β-胡蘿蔔素中之至少一者以提供約0.001mg/L至約5mg/L,包括約0.01mg/L至約1mg/L,且包括約0.1mg/L至
約0.5mg/L之類胡蘿蔔素總量。更特定而言,嬰兒配方包含葉黃素,其量為0.001μg/mL至5μg/mL,包括0.001μg/mL至0.500μg/mL,包括0.01μg/mL至0.250μg/mL,包括0.025μg/mL至0.20μg/L,且亦包括0.044μg/mL至5μg/mL葉黃素。亦通常較佳地,嬰兒配方包含0.001μg/mL至5μg/mL,包括0.01μg/mL至0.500μg/mL,包括0.05μg/mL至0.250μg/mL,包括0.055μg/mL至0.130μg/mL番茄紅素,且亦包括0.0185μg/L至5μg/L番茄紅素。亦通常較佳地,嬰兒配方包含0.001μg/mL至5μg/mL,包括0.001μg/mL至0.500μg/mL,包括0.01μg/mL至0.300μg/L β-胡蘿蔔素,包括0.025μg/L至0.200μg/mL β-胡蘿蔔素,且亦包括0.034μg/mL至約5μg/mL β-胡蘿蔔素。應瞭解,此等量之β-胡蘿蔔素、葉黃素、玉米黃素及番茄紅素之任何組合可包括於本發明之嬰兒配方中。其他類胡蘿蔔素可視情況包括於如本文中所述之嬰兒配方中。本文中所述之嬰兒配方中所包括之任一種或所有類胡蘿蔔素均可來自天然來源或人工合成。
所選組合中之類胡蘿蔔素各可得自用於嬰兒配方中之任何已知或其他適合物質來源,且各可個別或一起或以任何組合提供且形成許多來源,包括諸如含有其他維生素或礦物質與一或多種如本文中所述之類胡蘿蔔素組合之多種維生素預混物的來源。葉黃素、番茄紅素、β-胡蘿蔔素或其組合之一些適合來源的非限制性實例包括LycoVit®番茄紅素(得自BASF,Mount Olive,NJ),呈油、粉末或珠粒形式
之Lyc-O-Mato®番茄萃取物(得自LycoRed Corp.,Orange,NJ),β-胡蘿蔔素、葉黃素或番茄紅素(得自DSM Nutritional Products,Parsippany,NJ),FloraGLO®葉黃素(得自Kemin Health,Des Moines,IA),Xangold®天然葉黃素酯(得自Cognis,Cincinnati,OH),及Lucarotin® β-胡蘿蔔素(得自BASF,Mount Olive,N.J)。
除本文中所述之核苷酸及/或類胡蘿蔔素外,本發明之低卡路里嬰兒配方可進一步包含一或多種多量養分。多量養分包括蛋白質、脂肪、碳水化合物及其組合。適合用於本文中之多量養分包括已知用於或另外適合用於口服營養產品中之任何蛋白質、脂肪、碳水化合物或其來源,其限制條件為多量養分安全且有效地用於經口投與嬰兒且另外與嬰兒配方中之其他成份相容。本文中所述之多量養分必要時可由熟習此項技術者基於本文中之揭示內容來調整以獲得所需熱量密度及蛋白質含量。
儘管蛋白質、脂肪及碳水化合物之總濃度或量可視產品形式(例如粉末或即食液體)及所欲使用者之目標膳食需要而變,但該等濃度或量最通常屬於下表中所述之具體範圍之一內(各數值前加上術語「約」),包括如本文中所述之任何其他必需脂肪、蛋白質及或碳水化合物成份。
對於粉末實施例,下表A中之量為粉末復原後之量。
或者或另外,嬰兒配方中之碳水化合物、脂肪及蛋白質的含量及量(無論粉末配方或液體即食或濃縮液體)亦可表徵為嬰兒配方中之總卡路里百分比。用於本發明之嬰兒配方的此等多量養分最通常調配於下表B中所述之任何熱量範圍(各數值前加上術語「約」)。
除本文中所述之核苷酸及/或類胡蘿蔔素外,本發明之嬰兒配方亦可包含蛋白質。任何已知或另外適合之蛋白質或蛋白質來源可包括於本發明之嬰兒配方中,其限制條件為該等蛋白質適合用於餵養嬰兒及尤其新生兒。
適合用於嬰兒配方中之蛋白質或其來源的非限制性實例包括水解、部分水解或非水解蛋白質或蛋白質來源,其可來源於任何已知或另外適合來源,諸如乳(例如酪蛋白、乳清)、動物(例如肉、魚)、穀類(例如稻米、玉米)、蔬菜(例如大豆)或其組合。該等蛋白質之非限制性實例包括分
離乳蛋白、如本文中所述之乳蛋白濃縮物、分離酪蛋白、廣泛水解酪蛋白、乳清蛋白、酪蛋白鈉或鈣、全牛乳、部分或全脫脂乳、分離大豆蛋白、大豆蛋白濃縮物等。用於本文中之蛋白質亦可包括已知用於營養產品中之游離胺基酸或完全或部分由其替代,其非限制性實例包括L-丙胺酸、L-天冬胺酸、L-麩胺酸、甘胺酸、L-組胺酸、L-異白胺酸、L-白胺酸、L-***酸、L-脯胺酸、L-絲胺酸、L-蘇胺酸、L-纈胺酸、L-色胺酸、L-麩醯胺酸、L-酪胺酸、L-甲硫胺酸、L-半胱胺酸、牛磺酸、L-精胺酸、L-肉鹼及其組合。用於本文中所述之嬰兒配方中的尤其較佳蛋白質來源包括脫脂乳及乳清蛋白濃縮物。在一特定較佳實施例中,脫脂乳及乳清蛋白濃縮物組合用於嬰兒配方中。
在一些實施例中,本發明之嬰兒配方包括與習知足月兒及早產兒配方相比減少量之蛋白質。舉例而言,低蛋白質嬰兒配方包括每公升配方小於14.0公克蛋白質,包括每公升配方約5.0至約10.0公克蛋白質,且包括每公升配方約7.6至約10.0公克蛋白質之量的蛋白質。
除本文中所述之核苷酸及/或類胡蘿蔔素外,本發明之嬰兒配方亦可包含脂肪來源。適合用於本文中所述之嬰兒配方中的脂肪來源包括適合用於口服營養產品且與該等產品之必需要素及特點相容的任何脂肪或脂肪來源,其限制條件為該等脂肪適合於餵養嬰兒。
適合用於本文中所述之嬰兒配方中之脂肪或其來源的非
限制性實例包括椰子油、分餾椰子油、大豆油、玉米油、橄欖油、紅花子油、高油酸紅花子油、高GLA紅花子油、油酸、MCT油(中鏈三酸甘油酯)、葵花籽油、高油酸葵花籽油、結構化三酸甘油酯、棕櫚油及棕櫚仁油、棕櫚油精(palm olein)、菜籽油、亞麻籽油、琉璃苣籽油、月見草油、黑醋栗籽油、轉殖基因油來源、水產油(例如金槍魚、沙丁魚)、魚油、真菌油、海藻油、棉籽油及其組合。在一個實施例中,適合之脂肪或其來源包括油及油摻合物,包括長鏈多不飽和脂肪酸(LC-PUFA)。可包含之一些非限制性特定多不飽和酸包括例如二十二碳六烯酸(DHA)、二十碳四烯酸(ARA)、二十碳五烯酸(EPA)、亞麻油酸(LA)及其類似物。二十碳四烯酸及二十二碳六烯酸之非限制性來源包括水產油、來源於蛋類之油、真菌油、海藻油及其組合。尤其較佳脂肪來源包括高油酸紅花子油、大豆油及椰子油,其均可與ARA及/或DHA油組合使用。
在一個較佳實施例中,嬰兒配方包括高油酸紅花子油、大豆油及椰子油與ARA油及DHA油組合的組合。
本發明之嬰兒配方可包含適合用於口服營養產品(諸如嬰兒配方)中且與該產品之必需要素及特點相容之任何碳水化合物。
適合用於本文中所述之嬰兒配方中之碳水化合物或其來源的非限制性實例可包括麥芽糊精,水解、完整或改質之澱粉或玉米澱粉,葡萄糖聚合物,玉米糖漿,玉米糖漿固
體,來源於稻米之碳水化合物,稻米糖漿,來源於豌豆之碳水化合物,來源於馬鈴薯之碳水化合物,木薯澱粉,蔗糖,葡萄糖,果糖,乳糖,高果糖玉米糖漿,蜂蜜,糖醇(例如麥芽糖醇、赤藻糖醇、山梨糖醇),人工甜味劑(例如蔗糖素、乙醯磺胺酸鉀、甜菊),難消化寡醣(諸如果寡醣(FOS))及其組合。在一個實施例中,碳水化合物可包括DE值小於20之麥芽糊精。一種較佳碳水化合物為乳糖。
本發明之嬰兒配方可進一步包含可改良產品之物理、化學、美學或加工特徵或在用於目標群體時充當醫藥或其他營養組份之其他視情況選用之成份。許多該等視情況選用之成份為已知的或另外適合用於醫學食物或其他營養產品或醫藥劑型中且亦可用於本文之組合物中,其限制條件為該等視情況選用之成份對於經口投藥為安全的且與所選產品形式中之必需及其他成份相容。
該等視情況選用之成份的非限制性實例包括防腐劑、抗氧化劑、乳化劑、緩衝液、果寡醣、半乳寡醣、人乳寡醣及其他益菌助生質、醫藥活性劑、如本文中所述之其他養分、著色劑、調味劑、增稠劑及穩定劑、乳化劑、潤滑劑等及其組合。
流動劑或抗結塊劑可包括於如本文所述之粉末嬰兒配方中以延緩粉末隨時間而凝集或結塊且使粉末實施例易於自其容器流動。已知或另外適合用於營養粉末或產品形式之任何已知的流動劑或防結塊劑均適合用於本文中,其非限
制性實例包括磷酸三鈣、矽酸鹽及其組合。營養產品中之流動劑或防結塊劑的濃度視產品形式、其他所選成份、所需流動性質等而變,但範圍最通常為以組合物之重量計,約0.1%至約4%,包括約0.5%至約2%。
穩定劑亦可包括於嬰兒配方中。已知或另外適合用於營養產品中之任何穩定劑亦適合用於本文中,其一些非限制性實例包括樹膠,諸如三仙膠。穩定劑可佔嬰兒配方之約0.1重量%至約5.0重量%,包括約0.5重量%至約3重量%,包括約0.7重量%至約1.5重量%。
本發明之嬰兒配方可藉由用於製備所選產品固體或液體形式之任何已知或另外的有效製造技術來製備。已知多種該等技術用於任何既定產品形式(諸如營養液或粉末)且可容易地由一般技術者應用於本文中所述之嬰兒配方。
本發明之嬰兒配方因此可藉由各種已知或另外的有效調配或製造方法中之任一者來製備。舉例而言,在一種適合之製造方法中,製備至少兩種各別漿料,隨後將其摻合在一起,進行熱處理,標準化且最終進行滅菌以形成殺菌釜滅菌嬰兒配方或經無菌處理且填充以形成無菌嬰兒配方。或者,漿料可摻合在一起,進行熱處理,標準化,進行第二次熱處理,蒸發以移除水且噴霧乾燥以形成粉末嬰兒配方。
所形成之漿料可包括碳水化合物-礦物質(carbohydrate-mineral,CHO-MIN)漿料及脂肪包蛋白質(protein-in-fat,
PIF)漿料。最初,CHO-MIN漿料藉由使所選碳水化合物(例如乳糖、半乳寡醣等)在攪拌下溶解於熱水中,接著添加礦物質(例如檸檬酸鉀、氯化鎂、氯化鉀、氯化鈉、氯化膽鹼等)來形成。使所得CHO-MIN漿料保持持續加熱及適度攪拌直至其稍後與其他所製備之漿料摻合。
PIF漿料藉由加熱及混合油(例如高油酸紅花子油、大豆油、椰子油、單酸甘油酯等)及乳化劑(例如大豆卵磷脂),接著在持續加熱及攪拌下添加油溶性維生素、混合類胡蘿蔔素、蛋白質(例如乳蛋白濃縮物、乳蛋白水解產物等)、角叉菜膠(若存在)、碳酸鈣或磷酸三鈣(若存在)以及ARA油及DHA油(在一些實施例中)來形成。使所得PIF漿料保持持續加熱及適度攪拌直至其稍後與其他所製備之漿料摻合。
接著加熱水,在適當攪拌下與CHO-MIN漿料、脫脂乳(若存在)及PIF漿料組合。將所得摻合物之pH值調整至6.6-7.0,且使摻合物保持在適度加熱攪拌下。在一些實施例中,在此階段添加ARA油及DHA油。
接著使組合物經受高溫短時(high-temperature short-time,HTST)加工,期間對組合物進行熱處理,乳化及均質化,接著冷卻。添加水溶性維生素、任何痕量礦物質及抗壞血酸,必要時,將pH值調整至所需範圍,添加調味劑(若存在),且添加水以達成所需總固體含量。對於無菌嬰兒配方,乳液經由無菌加工器接受第二次熱處理,冷卻,接著無菌封裝於適合容器中。對於殺菌釜滅菌嬰兒配方,
將乳液封裝於適合容器中且最終滅菌。在一些實施例中,乳液可視情況進一步進行稀釋,熱處理,且封裝以形成所需即食或濃縮液體,或可進行熱處理,接著加工且封裝為可復原粉末(例如噴霧乾燥、乾式混合、聚結)。
噴霧乾燥粉末嬰兒配方或乾式混合粉末嬰兒配方可藉由適合於製備及調配營養粉之已知或另外的有效技術之任何集合來製備。舉例而言,當粉末嬰兒配方為噴霧乾燥營養粉時,噴霧乾燥步驟可同樣包括任何已知或另外的適合用於製備營養粉之噴霧乾燥技術。已知許多不同噴霧乾燥方法及技術用於營養學領域中,其均適合用於製造本文中之噴霧乾燥粉末嬰兒配方。在乾燥後,成品粉末可封裝於適合容器中。
低卡路里嬰兒配方及低卡路里及低蛋白質本發明之嬰兒配方可經口投與嬰兒,包括足月兒、早產兒及/或新生兒。低卡路里嬰兒配方可作為嬰兒營養來源投與及/或可用於預防及/或減少如本文中所論述之後續生命中一或多種可能發炎性相關疾病或病狀之發展及/或發作及/或使其減至最少及/或消除。可有效利用本文中所述之嬰兒配方的一般嬰兒群體之一個子類包括後續生命中易患本文中所述之一或多種疾病或病狀(包括肥胖)或處於患該等疾病或病狀之風險中(由於包括家族史等某些狀況,與一般嬰兒群體相比,處於患該疾病或病狀之高風險中)的彼等嬰兒。易患該疾病或病狀或處於患該疾病或病狀之風險中的
此等嬰兒可稱為在抵抗後續生命中患該疾病或病狀方面「需要」幫助(或「有需要」係指所需之幫助)。本發明之方法尤其有關具有本文中所述之該疾病及病狀之家族史,及尤其肥胖或糖尿病或胰島素控制問題之家族史的嬰兒,因為家族史可高度指示後續生命中個體可預期面對之疾病/病狀。
基於上文,因為本發明之一些方法實施例係有關嬰兒之特定子群或子類(亦即,在對付其後續生命中易患之一或多種特定疾病或特定病狀方面「需要」幫助之嬰兒的子群或子類),並非所有嬰兒均可得益於本文中所述之所有方法實施例,因為並非所有嬰兒將屬於如本文中對於某些疾病或病狀所述之嬰兒的子群或子類。
嬰兒配方通常將以適合於嬰兒年齡之攝取體積每日投與。舉例而言,本發明之方法可包括向嬰兒以本文中所述之平均攝取體積投與本發明之一或多種低卡路里或低卡路里/低蛋白質配方。在一些實施例,在生命最初數週期間提供新生兒以遞增之配方體積。該等體積最通常在生命第一天左右期間在平均至多約100毫升/天範圍內;在三個月新生兒餵養期之其餘時間期間為平均至多約200至約700毫升/天,包括約200至約600毫升/天,且亦包括約250至約500毫升/天。然而,應理解,該等體積可視特定新生兒及其在生命最初數週或數月期間之獨特營養需要以及所投與嬰兒配方之特定養分及熱量密度而顯著不同。
在一些實施例,本發明之方法可有關生命最初數天、數
週或數月期間之嬰兒。本文中所述之低卡路里嬰兒配方希望投與嬰兒之持續時間為至少生命第一週,更希望為在至少生命最初兩週期間,更希望為在至少生命最初一或兩個月期間,更希望為至少生命最初四個月期間,且更希望為至少生命最初六個月期間,且包括至多生命第一年。之後,嬰兒可換成單獨的習知嬰兒配方或習知嬰兒配方與人乳之組合。熟習此項技術者基於本文中之揭示內容應瞭解,本文中所述之嬰兒配方可單獨使用,或與人母乳組合使用,或與其他嬰兒配方組合使用。
除非另外說明,否則用於本文所述方法中的嬰兒配方為營養配方且可呈任何產品形式,包括如上所述之即食液體、濃縮液體、復原粉末及其類似物。在嬰兒配方呈粉末形式之實施例中,該方法可進一步包含用水性媒劑(最通常為水或人乳)復原粉末以形成所需熱量密度,接著經口或經腸餵給嬰兒。用足量水或其他適合流體(諸如人乳)復原粉末狀配方以產生所需熱量密度以及適於餵養一名嬰兒之所需餵養體積。嬰兒配方亦可在使用之前經由殺菌釜或無菌方法滅菌。
在一個態樣中,本發明係有關一種向嬰兒提供營養之方法。該方法包含向嬰兒投與本發明之任一或多種低卡路里嬰兒配方。該等方法可包括每日投與嬰兒配方,包括以如前文所述之每日攝取體積投與。在一些實施例,嬰兒為新生兒。
在另一態樣中,嬰兒配方可投與如本文中所述之嬰兒以
減少嬰兒後續生命中一或多種長期不利健康效應。特別地,在一些實施例,嬰兒配方之投與量可降低早期生命中及後續生命中促發炎細胞激素表現及增加抗發炎性細胞激素。此外,投與此等配方可抑制發炎路徑,諸如NF-κB及MAPK,藉此減少發炎。藉由減少發炎(其可為發炎相關疾病及病狀之潛在機制),降低嬰兒後續生命中患病之風險,且在一些實施例中甚至可能預防該等疾病。在一些實施例中,本發明之嬰兒配方意欲用於減少或消除如本文中所論述之後續生命中特定不利健康效應,包括肥胖、2型糖尿病、胰島素抗性、非胰島素依賴性糖尿病、心血管疾病及動脈粥樣硬化。
以下實例說明本發明之嬰兒配方及方法的特定實施例及/或特點。該等實例僅出於說明之目的而給出且不理解為對本發明之限制,因為在不脫離本發明之精神及範疇的情況下可能存在其許多變化形式。除非另外說明,否則所有例示量均為以組合物總重量計之重量百分比。
除非另外說明,否則殺菌釜滅菌配方可根據本文中所述之製造方法來製備,為即食液體配方。
在此等實例中,製備2盎司殺菌釜滅菌嬰兒配方。可用於製備配方之成份陳述於下表1及2中。成份之量為每1000kg批量之量。
藉由製備至少兩種各別漿料來製備配方,稍後將該等漿料摻合在一起,熱處理,標準化,且最後滅菌。起初,藉由在74-79℃下將所選碳水化合物(例如乳糖、半乳寡醣)溶解於水中,隨後添加檸檬酸、氯化鎂、氯化鉀、檸檬酸鉀、氯化膽鹼及氯化鈉來製備碳水化合物-礦物質漿料。在49-60℃下使所得漿料保持適度攪拌直至其稍後與其他所製備之漿料摻合。
藉由在攪拌下將高油酸紅花子油、椰子油、單酸甘油酯及大豆軟磷脂組合且加熱至66-79℃來製備脂肪包蛋白質漿料。10-15分鐘之保持時間後,接著將大豆油、油溶性維生素預混物、混合類胡蘿蔔素預混物、角叉菜膠、維生素A、檸檬酸鈣、磷酸二鈣、ARA油、DHA油及乳清蛋白濃縮物添加至漿料中。在49-60℃下使所得漿料保持適度攪拌直至其稍後與其他所製備之漿料摻合。
將水加熱至49-60℃,接著在適度攪拌下與碳水化合物-礦物質漿料、脫脂乳及脂肪包蛋白質漿料組合。用氫氧化鉀調整所得摻合物之pH值。在49-60℃下使此摻合物保持適度攪拌。
將所得摻合物加熱至74-79℃,經由單級均質器乳化至900-1100psig,接著加熱至144-147℃,約5秒。使經加熱之摻合物通過快速冷卻器以使溫度降低至88-93℃,接著通過板式冷卻器以使溫度進一步降低至74-85℃。接著在2900-3100/400-600psig下使經冷卻之摻合物均質化,在74-85℃下保持16秒,接著冷卻至2-7℃。取得樣品以進行
分析測試。在2-7℃下使混合物保持攪拌。
分開製備水溶性維生素(WSV)溶液及抗壞血酸溶液且添加至經加工之摻合漿料中。藉由在攪拌下將以下成份添加至水中來製備維生素溶液:檸檬酸鉀、硫酸亞鐵、WSV預混物、L-肉鹼、硫酸銅、核黃素、肌醇及核苷酸-膽鹼預混物。藉由將氫氧化鉀及抗壞血酸添加至足以溶解成份之量的水中來製備抗壞血酸溶液。接著用氫氧化鉀將抗壞血酸溶液pH值調整至5-9。
用氫氧化鉀(由產品改變)將摻合物pH值調整至7.1-7.6之特定pH值範圍以達成最佳產品穩定性。接著將完成之產品填充至適合之容器中且進行熱滅菌。
方法
將8週齡雄性C57BL6/J小鼠(訂購自Jackson Labs,Bar Harbor,Maine)單個圈養且允許在研究開始前適應設施及對照膳食1週。將小鼠隨機分配至如下6個膳食組之一(每個膳食組n=8隻小鼠)
1. D12450B:對照膳食
2. D11083104:對照膳食+核苷酸+類胡蘿蔔素
3. D11083101:養分限制
4. D11083102:卡路里限制+核苷酸
5. D11083103:卡路里限制+類胡蘿蔔素
6. D11083104:卡路里限制+核苷酸+類胡蘿蔔素
由Research Diets,Inc.New Brunswick New Jersey根據表
3中所述之規格調配膳食。在送至University of Illinois,Urbana Champaign(UIUC)前在Abbott Nutrition就關注化合物對膳食進行測試。
隨意餵養對照組中之小鼠,其中每日(週一至週六,在週日提供兩天的食物分配量)稱重及記錄食物攝取。所有實驗餵養組(3-6)接受對照組(1)之90重量%平均每日攝取。每日藉由移除料斗中或草墊上可見之任何食物且用對照膳食之90重量%替代來給予實驗膳食(3-6)。每週清掃及更換籠子。出於收集組織之目的,餵養間隔一週以內。
餵養30天後,經由腹膜內注射用脂多醣(「LPS」)(100μg/kg)或磷酸鹽緩衝生理鹽水(「PBS」)(體積匹配)處理小鼠且返回其各自籠中。處理4小時後,灌注及收集肝、脾、血液(經EDTA處理)及腦。收集肝且根據來自UIUC Keck Center之製造商之指導及說明書在DNA微陣列晶片上分析。在RNAlater®中加工脾、血液、腦及肝外樣品且儲存於專用-20℃冷凍器中以供將來分析。
分析:
關於分析,參考以下膳食:
1. LF(D12450B:對照膳食)
2. LFc+n(D11083104:對照膳食+核苷酸+類胡蘿蔔素)
3. 90% LF(D11083101:卡路里限制)
4. 90%+n(D11083102:卡路里限制+核苷酸)
5. 90%+c(D11083103:卡路里限制+類胡蘿蔔素)
6. 90%+c+n(D11083104:卡路里限制+核苷酸+類胡蘿蔔素)
億明達氏小鼠(Illumina's Mouse)WG-6 v2陣列(得自Illumina,San Diego,CA 92122 USA)具有45,281個獨特探針;超過一種探針可詢問單一基因,故該陣列上不存在45,281個獨特基因。由陣列上約45個珠粒量測各探針,且使用億明達氏Genome Studio(V2011.1,基因表現模組V1.9.0)不經背景修正或校正而輸出各探針之所有珠粒的平均值。另外,輸出「偵測P值」,其為對陣列上各探針之個別珠粒值與所有陰性對照珠粒以觀察探針之表現值是否高於背景進行比較的t檢驗之結果。
使用limma(微陣列數據之線性模型)套件進行原始探針值及R統計套件(v2.14.1)中之偵測P值的輸入。對原始探針值使用所謂「neqc」之預加工方法,其進行基於模型之背景修正,分位數陣列間校正,接著將所得值進行log2轉化。為保持用於進一步分析,探針必須稱為「存在」於任何12個處理×膳食組合中之4個重複實驗中的至少2個中。45,281個探針中之21,457個通過此過濾且使用具有經驗貝葉斯修正(Bayes correction)之統計模型測試其差異表現以幫助改良偵測差異之能力;模型亦調整用於同一載片上之陣列間的修正(WG-6格式具有每個載片6個陣列)。模型首先估計12個處理×膳食組合各自之表現值,接著自模型獲得特定比較作為對比。12個處理×膳食組間存在許多可能的比較;因此,將其組織為7個不同組:
1. LPSvPBS-在各膳食中PS相對於PBS處理之成對比較;總共6個比較。
2. PBS膳食-在PBS處理中不同膳食之成對比較。
3. LPS膳食-在LPS處理中不同膳食之成對比較。
4. PBS_2x2_90CandN-在PBS處理中將C及/或N添加至90% LF中之2×2階乘比較。比較包括主要效應與相互作用項。
5. LPS_2x2_90CandN-在LPS處理中將C及/或N添加至90% LF中之2×2階乘比較。比較包括主要效應與相互作用項。
6. PBS_2x2_CalAdd-在PBS處理中卡路里含量(90%相對於LF)及C+N(是相對於否)之2×2階乘比較。比較包括主要效應與相互作用項。
7. LPS_2x2_CalAdd-在LPS處理中卡路里含量(90%相對於LF)及C+N(是相對於否)之2×2階乘比較。比較包括主要效應與相互作用項。
進一步分析PBS及LPS所有成對(以上#2及3)資料集以確定受膳食處理影響之關注基因。選擇成對比較3v2、4v2、5v2及6v2以觀察與3v2相比4v2、5v2及6v2之間是否存在變化倍數之任何相對差異。
1. 取出3v2、4v2、5v2及6v2比較。
2. 按FDR p值將各清單分類。
3. 鑑定在3v2中FDR p值0.05之基因。
4. 鑑定在4v2、5v2及6v2中FDR p值0.05之基因。
5. 將來自步驟4之各個成對比較中之基因與步驟3中之基因匹配。
a. 基於探針ID號使用Excel中之Countif功能進行匹配。
6. 鑑定具有變化倍數之相對差異的基因(陽性更大或陰性更大)。
此使得與3v2相比對於4v2鑑定出25個基因;與3v2相比對於5v2鑑定出37個基因;且與3v2相比對於6v2鑑定出23個基因(圖1),該等基因具有變化倍數之相對差異。針對與假設之相關性將此等基因手動分類。搜索方法包括使用PubMed搜索以及文獻搜索中之基因ID號。此搜索鑑定三個具有變化倍數之相對差異的基因候選物,其暗示類胡蘿蔔素及/或核苷酸對低卡路里膳食之益處。
所鑑定之基因為Prkab1/AMPKβ、血清澱粉狀蛋白A(Saa)及介白素-1α/β(IL-1α/β)。圖2-4說明與參考膳食相比關注膳食之變化倍數的絕對變化量。AMPK充當「開啟」ATP消耗分解代謝路徑之調節酶。已顯示肝臟AMPK調節胰島素及葡萄糖代謝。已顯示肥胖的人降低與肥胖相關發炎有關之AMPK的脂肪組織表現。小鼠中AMPK之全身基因剔除(KO)導致食慾下降及防止肥胖。此肥胖減少係歸因於AMPK之下丘腦表現降低,從而導致攝食量減少(1)。然而,AMPK之組織特異性(巨噬細胞)增加與餵食高脂肪膳食(HFD)之小鼠的發炎及胰島素抗性減少有關(2)。圖2說明與餵食添加核苷酸之低卡路里膳食的小鼠相比餵食低卡路里膳食之經LPS處理小鼠中的Prkab1/AMPKβ表現
相對增加(1.42相對於具有類胡蘿蔔素及核苷酸之對照膳食的1.58變化倍數)。因此,吾人之假設為:將核苷酸添加至低卡路里膳食中可見的組織特異性(肝臟)增加可提供類似於Galic等人(2)之益處。
血清澱粉狀蛋白A(SAA)為已報導在肥胖及胰島素抗性人類之血漿中增加的急性期蛋白(3)。最新綜合分析及系統綜述說明在11項橫斷面研究中BMI與SAA含量之間的強相關性(4)。SAA之慢性升高與動脈粥樣硬化之風險增加相關且見於動脈粥樣硬化病變中(5),已顯示其促進內皮功能障礙(6)。Scheja等人證明在小鼠餵食1週HFD內增加且用SAA離體處理脂肪細胞可導致胰島素信號傳導及葡萄糖轉運之衰減(3)。已顯示血清澱粉狀蛋白A在肥胖個體體重減輕後顯著減少且此等患者在體重減輕後之胰島素敏感性改善與SAA減少有關(7)。圖3說明將類胡蘿蔔素、核苷酸及/或兩者添加至低卡路里膳食中可導致Saa1-4之表現相對降低。因此,吾人之假設為:肝臟中SAA表現之降低(圖3)可對發展肥胖、胰島素抗性及/或動脈粥樣硬化提供保護性益處。
介白素1α/β(IL-1)為促炎性細胞激素,已顯示其在肥胖之HFD及遺傳模型中增加。IL-1增加與肥胖中所見之慢性低度發炎有關,認為慢性低度發炎為肥胖與其許多共同罹病(諸如胰島素抗性及動脈粥樣硬化)之間的關鍵聯繫。糖尿病小鼠具有由IL-1β反調節損失引起之IL-1β介導性免疫反應增大(8)。IL-1α之多形現象與健康肥胖個體之肥胖相
關(9,10)。已顯示IL-1α在肥胖小鼠(HFD模型)中增加以及三酸甘油酯亦急性增加(10)。與具有類胡蘿蔔素及核苷酸之對照膳食相比,在餵食添加有類胡蘿蔔素、核苷酸及/或兩者之低卡路里膳食的經LPS處理小鼠中IL-1α表現相對降低。另外,對於經PBS處理小鼠中之IL-1β可見,此相同降低表現模式(圖4)。IL-1α/β之減少具有抗發炎性,且吾人之假設為:如將類胡蘿蔔素及/或核苷酸添加至低卡路里膳食中所見,此減少將提供額外抗發炎性益處及保護以防肥胖及其免疫介導性共同罹病。
參考文獻
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2. Galic S, Fullerton MD, Schertzer JD, Sikkema S, Marcinko K, Walkley CR, et al. Hematopoietic AMPK betal reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. J Clin Invest. 2011 Dec;121(12):4903-15.
3. Scheja L, Heese B, Zitzer H, Michael MD, Siesky AM, Pospisil H, et al. Acute-phase serum amyloid A as a marker of insulin resistance in mice. Exp Diabetes Res. 2008;2008:230837.
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Association between serum amyloid A and obesity: a meta-analysis and systematic review. Inflamm Res. 2010 May;59(5):323-34.
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6. Witting PK, Song C, Hsu K, Hua S, Parry SN, Aran R, et al. The acute-phase protein serum amyloid A induces endothelial dysfunction that is inhibited by high-density lipoprotein. Free Radic Biol Med. 2011 Oct l;51(7):1390-8.
7. Yang RZ, Lee MJ, Hu H, Pollin TI, Ryan AS, Nicklas BJ, et al. Acute-phase serum amyloid A: an inflammatory adipokine and potential link between obesity and its metabolic complications. PLoS Med. 2006 Jun;3(6):e287.
8. O'Connor JC, Satpathy A, Hartman ME, Horvath EM, Kelley KW, Dantzer R, et al. IL-1 beta-mediated innate immunity is amplified in the db/db mouse model of type 2 diabetes. J Immunol. 2005 Apr 15;174(8):4991-7.
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2011;6(12):e29524.
圖1描繪PBS及LPS之分析,所有的成對比較。
圖2描繪在添加核苷酸之情況下Prkab1/AMPKβ之相對增加。
圖3描繪在添加類胡蘿蔔素、核苷酸或兩者之情況下Saa1-4之相對減少。
圖4描繪在添加類胡蘿蔔素、核苷酸或兩者之情況下IL-1之相對減少。
Claims (14)
- 一種減少後期生命中肥胖之方法,該方法包含向有需要之嬰兒在生命第一年中投與嬰兒配方,其中該嬰兒配方之能量含量小於650Kcal/L且包含至少一種選自由葉黃素、番茄紅素及玉米黃素組成之群之類胡蘿蔔素。
- 如請求項1之方法,其中該嬰兒配方進一步包含每公升組合物小於14.0公克之蛋白質。
- 如請求項1或2之方法,其中該嬰兒配方包含0.001mg/L至5mg/L類胡蘿蔔素。
- 如請求項1或2之方法,其中該類胡蘿蔔素為葉黃素。
- 如請求項1之方法,其包含至少一種核苷酸及至少一種類胡蘿蔔素,且其中該類胡蘿蔔素為葉黃素。
- 如請求項2之方法,其中該嬰兒配方包含每公升配方5.0公克至10.0公克之蛋白質。
- 如請求項3之方法,其中該嬰兒配方包含0.01mg/L至1mg/L類胡蘿蔔素。
- 一種藉由改善胰島素敏感性以減少後期生命中肥胖之方法,該方法包含向有需要之嬰兒在生命第一年中投與嬰兒配方,其中該嬰兒配方之能量含量小於650Kcal/L且包含至少一種核苷酸及至少一種類胡蘿蔔素。
- 如請求項8之方法,其中該嬰兒配方進一步包含每公升配方小於14.0公克之蛋白質。
- 如請求項8或9之方法,其中該嬰兒配方包含10mg/L至200mg/L核苷酸。
- 如請求項8或9之方法,其中該嬰兒配方包含0.001mg/L至5mg/L類胡蘿蔔素。
- 如請求項8或9之方法,其中該類胡蘿蔔素係選自由葉黃素、番茄紅素、玉米黃素、β-胡蘿蔔素及其組合組成之群。
- 如請求項8或9之方法,其中該核苷酸係選自由5'單磷酸胞苷、5'單磷酸鳥苷二鈉、5'單磷酸尿苷二鈉、5'單磷酸腺苷及其組合組成之群。
- 如請求項8或9之方法,其中該類胡蘿蔔素為葉黃素。
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CN (1) | CN104114043B (zh) |
BR (1) | BR112014016135A8 (zh) |
CA (1) | CA2861547A1 (zh) |
HK (1) | HK1203038A1 (zh) |
IL (1) | IL233298A0 (zh) |
MX (1) | MX2014007936A (zh) |
PH (1) | PH12014501493A1 (zh) |
SG (1) | SG11201403712XA (zh) |
TW (1) | TWI472300B (zh) |
WO (1) | WO2013180747A2 (zh) |
Families Citing this family (2)
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EP2797432A2 (en) | 2011-12-27 | 2014-11-05 | Abbott Laboratories | Use of reduced calorie infant formula containing nucleotides and/or carotenoids for reducing adverse health effects later in life |
CN115227706B (zh) * | 2022-06-08 | 2023-12-29 | 陈玉松 | 5’-单磷酸核苷酸组合物在制备消脂减肥功能食品和药物中的应用 |
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TW200845917A (en) * | 2006-12-15 | 2008-12-01 | Nestec Sa | Nutritional composition |
US20090118227A1 (en) * | 2007-11-07 | 2009-05-07 | Bristol-Myers Squibb Company | Carotenoid-containing compositions and methods |
CN101951794A (zh) * | 2007-12-21 | 2011-01-19 | N.V.努特里奇亚 | 鞘髓磷脂和非消化性碳水化合物改善肠道微生物群的用途 |
TW201121431A (en) * | 2009-12-01 | 2011-07-01 | Abbott Lab | Soy protein-based nutritional formula with superior stability |
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JP5031156B2 (ja) | 2001-09-20 | 2012-09-19 | カゴメ株式会社 | 抗肥満剤 |
US7090879B2 (en) * | 2004-03-18 | 2006-08-15 | Abbott Laboratories | Nutritional formula containing select carotenoid combinations |
EP1656839A1 (en) * | 2004-11-11 | 2006-05-17 | N.V. Nutricia | Nutrition containing lipid blend |
US7829126B2 (en) | 2005-10-26 | 2010-11-09 | Abbott Laboratories | Infant formulas containing docosahexaenoic acid and lutein |
PT1800675E (pt) | 2005-12-23 | 2011-08-30 | Nutricia Nv | COMPOSIÇÃO CONTENDO ÁCIDOS GORDOS POLI-INSATURADOS, PROTEÍNAS E MANGANjS E/OU MOLIBDÉNIO PARA O MELHORAMENTO DA COMPOSIÇÃO DA MEMBRANA |
MX2010011995A (es) * | 2008-05-01 | 2010-12-02 | Procter & Gamble | Metodos y estuches para el tratamiento de condiciones y trastornos inflamatorios del intestino. |
EP2413718B1 (en) * | 2009-04-01 | 2016-03-23 | Nestec S.A. | Use of arachidonic acid for the reduction of the risk of insulin resistance later in life |
EP2797432A2 (en) | 2011-12-27 | 2014-11-05 | Abbott Laboratories | Use of reduced calorie infant formula containing nucleotides and/or carotenoids for reducing adverse health effects later in life |
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2012
- 2012-12-04 EP EP12871602.4A patent/EP2797432A2/en not_active Withdrawn
- 2012-12-04 TW TW101145555A patent/TWI472300B/zh not_active IP Right Cessation
- 2012-12-04 BR BR112014016135A patent/BR112014016135A8/pt not_active IP Right Cessation
- 2012-12-04 MX MX2014007936A patent/MX2014007936A/es unknown
- 2012-12-04 SG SG11201403712XA patent/SG11201403712XA/en unknown
- 2012-12-04 WO PCT/US2012/067712 patent/WO2013180747A2/en active Application Filing
- 2012-12-04 CA CA2861547A patent/CA2861547A1/en not_active Abandoned
- 2012-12-04 CN CN201280070672.9A patent/CN104114043B/zh not_active Expired - Fee Related
- 2012-12-04 US US14/367,518 patent/US9474766B2/en not_active Expired - Fee Related
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2014
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- 2014-06-27 PH PH12014501493A patent/PH12014501493A1/en unknown
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TW200845917A (en) * | 2006-12-15 | 2008-12-01 | Nestec Sa | Nutritional composition |
US20090118227A1 (en) * | 2007-11-07 | 2009-05-07 | Bristol-Myers Squibb Company | Carotenoid-containing compositions and methods |
CN101951794A (zh) * | 2007-12-21 | 2011-01-19 | N.V.努特里奇亚 | 鞘髓磷脂和非消化性碳水化合物改善肠道微生物群的用途 |
TW201121431A (en) * | 2009-12-01 | 2011-07-01 | Abbott Lab | Soy protein-based nutritional formula with superior stability |
Also Published As
Publication number | Publication date |
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BR112014016135A2 (pt) | 2017-06-13 |
TW201328610A (zh) | 2013-07-16 |
US20150011498A1 (en) | 2015-01-08 |
CN104114043B (zh) | 2016-10-19 |
HK1203038A1 (zh) | 2015-10-16 |
NZ626947A (en) | 2016-01-29 |
CA2861547A1 (en) | 2013-12-05 |
US9474766B2 (en) | 2016-10-25 |
WO2013180747A2 (en) | 2013-12-05 |
WO2013180747A3 (en) | 2014-03-06 |
IL233298A0 (en) | 2014-08-31 |
BR112014016135A8 (pt) | 2017-07-04 |
EP2797432A2 (en) | 2014-11-05 |
PH12014501493A1 (en) | 2014-09-22 |
SG11201403712XA (en) | 2014-10-30 |
CN104114043A (zh) | 2014-10-22 |
MX2014007936A (es) | 2014-07-30 |
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