TW201717781A - 用於促進認知發展的營養組成物及方法 - Google Patents
用於促進認知發展的營養組成物及方法 Download PDFInfo
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Abstract
一種用於增強小兒個體認知發展的方法,該方法涉及對個體施用營養組成物,其包括高達7g/100Kcal之脂肪或脂質;高達5g/100Kcal之蛋白質或蛋白質等同物來源;0.06g/100Kcal至1.5g/100Kcal之強化乳製品;5mg/100Kcal至90mg/100Kcal之長鏈多不飽合脂肪酸的來源;及0.015g/100Kcal至1.5g/100Kcal之益菌生。
Description
本揭露係有關於藉由提供孩童營養組成物以促進孩童認知發展的方法,該營養組成物包括設計以提升及支援免疫功能、胃腸健康及腦功能之濃度的特定組合之功能性成分,可結合以上所有以改善認知發展。更具體地,本揭露之營養組成物包括強化乳製品,諸如強化乳清蛋白濃縮物(eWPC)、長鏈多不飽合脂肪酸及益菌生,亦隨意地與乳鐵蛋白、短鏈脂肪酸及維生素B12之一或多者結合。本文中所述之營養組成物可適用於施予小兒個體以支援及促進認知發展。
人乳含有數種組分,其有助於嬰兒發育及腦部發展。但是,牛乳及以牛乳為基礎的許多市售嬰兒配方奶粉提供的一些該等組分的量低於所需,如長鏈多不飽合脂肪酸、乳鐵蛋白及極性脂質。因此,有需要提供更接近模擬人乳的組成物和品質,以最佳化嬰兒及孩童的腦部發
育及發展。
因此,其可用於提供能夠提供改善的神經系統的健康及功能(包括早年的認知、語言發展及運動技巧)的方法與營養組成物。其亦可用於達到提升及支援免疫功能、胃腸健康及腦部功能的結果的方法。
因此,本揭示提供用於支援個體的認知發展的方法、包括施予個體包括強化乳製品、長鏈多不飽合脂肪酸、及益菌生的營養組成物,亦可選地與乳鐵蛋白、短鏈脂肪酸及維生素B12之一或多者組合。在一些實施例中,營養組成物亦包括脂肪或脂質、碳水化合物及蛋白質或蛋白質等同物來源。
簡要地說,本揭示係導向用於支援及促進小兒個體的功能性神經成熟的組成物及方法。本方法包括施予包含強化乳製品、長鏈多不飽合脂肪酸(LCPUFA)諸如二十二碳六烯酸(DHA)、及益菌生組成物之組合的組成物。更具體地,在特定實施例中,本揭示之營養組成物包含:高達約7g/100Kcal之脂肪或脂質;高達約5g/100Kcal之蛋白質或蛋白質等同物來源;約0.06g/100Kcal至1.5g/100Kcal之強化乳製品;約5mg/100Kcal至90mg/100Kcal之LCPUFA;及約0.015g/100Kcal至1.5g/100Kcal之益菌生。
在一些實施例中,強化乳製品包含eWPC。此外,在一些實施例中,營養組成物進一步包含約5mg/100Kcal至約300mg/100Kcal之乳鐵蛋白。小兒個體可以是嬰兒或孩童,且營養組成物可以嬰兒配方奶粉或成長奶粉提供(其意指包括嬰幼兒後續配方奶粉(follow-on formula)或較大嬰幼兒配方奶粉(follow-up formula))。
強化乳製品在本揭示之上下文中意指富含乳脂肪球膜(MFGM)組分,諸如MFGM蛋白及脂質。強化乳製品可藉由如非人(如,牛)乳分餾形成。強化乳製品具有介於20%及90%之間範圍的總蛋白質濃度,更佳地介於68%及80%,其中的MFGM蛋白質介於3%及50%;在一些實施例中,MFGM蛋白質由7%至13%之強化乳製品蛋白質含量製成。強化乳製品亦包含0.5%至5%(而有時候1.2%至2.8%)之唾液酸、2%至25%(而在一些實施例中為4%至10%)之磷脂、0.4%至3%之神經鞘磷脂、0.05%至1.8%、而在特定實施例中0.10%至0.3%之神經節苷脂及0.02%至約1.2%、更佳地0.2%至0.9%之膽固醇。因此,強化乳製品包括比牛及其他非人乳品更高濃度之所欲組分。
乳品(諸如牛乳)為複雜的乳狀物,其包含數種類別之組分,其滿足對消費者的營養需求及/或提供特殊健康益處。乳品的脂肪組分以0.1至10微米尺寸範圍之小球體形式呈現。脂肪球包含約98%三酸甘油酯(TAG,動物中主要儲存能量的形式)且被乳脂肪球膜包
圍並安定化,乳脂肪球膜為衍生自內質網膜及細胞膜。
乳脂肪球膜是由三層脂質結構組成,三層脂結構包括磷脂、蛋白質、醣蛋白、三酸甘油酯、極性脂質、膽固醇、酵素及其他組分的複雜混合物,其在傳統嬰兒配方奶粉及成長奶粉中通常是不充足的。
MFGM中的極性脂質是由以下所組成的:(i)甘油磷脂諸如卵磷脂(PC)、磷脂醯乙醇胺(PE)、磷脂質絲胺酸(PS)及磷脂酸肌醇(PI),及其衍生物,及(ii)鞘氨醇類或神經鞘脂類諸如神經鞘磷脂(SM)及醣化神經磷脂包含腦苷脂(含有不帶電糖的中性醣化神經磷脂)及神經節苷脂(GG,含有唾液酸的酸性醣化神經磷脂)及其衍生物。
磷脂醯乙醇胺為發現於生物膜中的磷脂,尤其在神經組織諸如大腦白質、神經、神經組織及脊髓中,其組成所有磷脂的45%。神經鞘磷脂為發現於動物細胞膜中的一種神經鞘脂類,尤其是在圍繞一些神經細胞軸突的膜狀髓鞘中。其通常由磷膽鹼與神經醯胺,或磷酸乙醇胺頭部基組成;因此,神經鞘磷脂亦可被歸類於神經鞘磷脂。在人類中,SM呈現約占所有神經鞘脂類的85%,且通常組成10至20莫耳%之漿膜脂質。神經鞘磷脂存在於動物細胞漿膜中且尤其主要是在圍繞且隔離一些神經的軸突的膜狀鞘之髓鞘中。
LCPUFA諸如DHA為ω3脂肪酸,其為人類大腦、大腦皮層、皮膚、精子、睪丸及視網膜的主要結構組分。DHA可經由α次亞麻油酸合成或直接自母乳或魚油中獲得。DHA為大腦及視網膜中最豐富的ω3脂肪酸。DHA在大腦中含有40%之多不飽合脂肪酸(PUFA)且在視網膜中含有60%的PUFA。神經元的漿膜的重量50%是由DNA組成。DHA在哺乳期間大量供應,且DHA濃度在人乳中為高的。人乳中的DHA濃度範圍占總脂肪酸0.07%至大於1.0%,平均約0.32%。若母親的飲食中魚類較多,人乳中的DHA濃度則較高。
咸信益菌生透過其影響GI微生物相而在中樞神經系統內改變生物胺及神經傳導物質的產生,且此種改變可解釋益菌生對社交技巧、焦慮及記憶功能的正面影響。因此咸信益菌生可與強化乳製品組分及LCPUFA合作地作用以增強大腦發育及促進神經元成熟。總結來說,揭示之營養組成物可藉由改變腸道菌群、優化大腦組成物、及改善各種與大腦相關的行為及功能而在嬰兒期與孩童期期間扮演重要角色。
應了解以上的一般性描述及以下詳細描述兩者呈現本揭露之實施例且意欲提供所保護之本揭示的本質與特性之理解的概述或框架。本描述用於解釋所保護之主題之原理及操作。其他及進一步的特徵與本揭示之優點,於閱讀以下揭露時對於本領域技術人員將是簡單明瞭的。
針對本揭露之實施例的參考文獻現在將詳細描述,其一或更多範例將闡述於下文中。以提供各範例的方式解釋本揭露之營養組成物且並非限制。事實上,熟悉本領域技術之人員將了解可對本揭露之教導做各種修飾及變化而不背離本揭示之範圍。舉例來說,所例示或描述之特徵作為一實施例之一部分,可與另一實施例使用以產生更進一步的實施例。
因此,其意圖為本揭露涵蓋此修飾及變化落入所附之申請專利範圍及其等同物之範圍內。本揭露之其他物件、特徵及態樣揭示於以下詳細描述中或於以下詳細描述顯而易見的。本領域一般技術之人員應了解本討論僅是示例性實施例的描述,且不意欲為限制本揭示更寬廣之態樣。
本揭露一般關於對小兒個體(即,嬰兒或孩童)的營養組成物之施予。此外,本揭露關於經由本文所揭示之營養組成物之施予來改善嬰兒或孩童的神經及認知健康與發育。
「營養組成物」意指滿足至少部分個體的營養需求之物質或配方。貫穿本揭露之「營養物」、「營養配方」、「腸內營養物」、及「營養補充品」等詞是用為營養組成物的非限制範例。此外,「營養組成物」可意指液體、粉末、膠狀物、膏狀物、固體、濃縮物、懸浮物或即開即用形式之腸內配方、口服配方、嬰兒用配方、小兒
個體配方、孩童配方、成長奶粉及/或成人用營養組成物。
「腸內」一詞意指可遞送通過胃腸道、或消化道,或在胃腸道或消化道內。「腸內施予」包括經口攝取、腸內攝取、幽門施予(transpyloric administration)、或任何其他方法施予至消化道內。「施予」比「腸內施予」範圍更廣且包括腸外施予或物質攝取至個體體內的任何其他施予路徑。
「小兒個體」意指不大於13歲的人類。在一些實施例中,小兒個體意指介於出生及8歲之間的人類個體。在其他實施例中,小兒個體意指介於1及6歲之間的人類個體。在更進一步實施例中,小兒個體意指介於6及12歲之間的人類個體。「小兒個體」一詞意指嬰兒(早產兒或足月)及/或孩童,如以下所述。
「嬰兒」意指自出生至不超過一年的範圍的人類個體且包括0至12個月經校正年齡的嬰兒。「經校正年齡」一詞意指嬰兒的實足年齡減掉該嬰兒早產的時間。因此,若是足月的話,經校正年齡為嬰兒年齡。嬰兒一詞包括低出生體重兒、非常低出生體重兒、極低出生體重兒及早產兒。「早產」意指嬰兒在第37週的孕期結束前出生。「晚期早產」意指嬰兒在介於第34週及第36週孕期之間出生。「足月」意指嬰兒在第37週的孕期結束後出生。「低出生體重兒」意指嬰兒出生體重低於2500克(接近5lbs、8盎司)。「非常低出生體重兒」意指嬰
兒出生體重低於1500克(接近3lbs、4盎司)。「極低出生體重兒」意指嬰兒出生體重低於1000克(接近2lbs、3盎司)。
「孩童」意指年齡範圍從12個月至13年的個體。在一些實施例中,孩童為介於1及12歲之年齡的個體。在其他實施例中,「孩童」一詞意指介於一及約六歲之間,或介於約七及約12歲之間的個體。在其他實施例中,「孩童」一詞意指介於12個月及約13年之任何年齡範圍之間。
「孩童營養產品」意指滿足孩童至少一部分營養需求的組成物。成長奶粉為孩童營養產品的範例,如同嬰幼兒後續配方奶粉及較大嬰幼兒配方奶粉。
「水解度」一詞意指藉由水解方法將胜肽鍵打斷的程度。針對營養組成物的水解蛋白質組分特徵目的之蛋白質水解度藉由量化選定之配方的蛋白質組分的胺基氮對總氮比例(AN/TN)而輕易地由配方領域中一般技術之人員決定。胺基氮組分藉由USP滴定法定量以決定胺基氮含量,而總氮組分由凱氏定氮法(Kjeldahl method)決定,其所有皆為分析化學領域中一般技術之人員所周知的方法。
「部分水解」一詞意指水解度大於0%但小於約50%。
「廣泛水解」一詞意指水解度大於或等於約50%。
「無蛋白質」一詞意指當由標準蛋白質偵測法諸如十二烷基(月桂基)硫酸鈉聚丙烯醯胺凝膠電泳(SDS-PAGE)或分子篩選層析(size exclusion chromatography)測量時不含有可量測之蛋白質的量。在一些實施例中,營養組成物實質上無蛋白質,其中「實質上無」在下文中定義。
「嬰兒配方奶粉」意指滿足嬰兒至少一部分營養需求的組成物。在美國,嬰兒配方奶粉的內容由闡述於21 C.F.R.第100、106及107章的聯邦法法規所決定。這些法規定義巨量營養素、維生素、礦物質及其他成分濃度,旨在於刺激人類母乳的營養及其他性質。
「成長奶粉」一詞意泛指意欲用作為多樣化飲食的營養組成物類別的一部分,用以支援年齡介於約1至約6歲之孩童正常生長及發育。如本文中所使用,「成長奶粉」一詞亦欲稱為「嬰幼兒後續配方奶粉」及「較大嬰幼兒配方奶粉」。
「以乳為基底」意指包含至少一組分,該組分自哺乳動物的乳腺汲取或搾取。在一些實施例中,以乳為基底的營養組成物營養組成物包含乳組分,該乳組分係源自馴養的有蹄動物、反芻動物或其他哺乳動物或其任何組合。再者,在一些實施例中,以乳為基底意指包含牛酪蛋白、乳清、乳糖或其任何組合。此外,「以乳為基底的營養組成物」可指任何組成物,包含本領域已知之任何乳衍生物或以乳為基底產物。
「乳」意指汲取或搾取自哺乳動物的乳腺之組分。在一些實施例中,營養組成物包含乳的組分,該乳係衍生自馴養的有蹄動物、反芻動物或其他哺乳動物或其任何組合。
「分餾程序」包括其中混合物的一定量被分為稱作餾份的數個較小量的任何處理。來自混合物及其他餾份兩者的餾份其組成物可能不同。分餾程序的範例包括,但不限於融化分餾(melt fractionation)、溶劑分餾(solvent fractionation)、超臨界流體分餾(supercritical fluid fractionation)及/或其組合。
「脂肪球」意指由磷脂及其他膜及/或血漿脂質及蛋白質圍繞的小量脂肪,其中脂肪本身可為任何植物性或動物性脂肪的組合。
「極性脂質」為天然膜的主要成分,其發生於所有生物體中。乳中的極性脂質(即,乳極性脂質)主要位於乳脂肪球膜中。極性脂質亦存在於諸如蛋、肉及植物之乳以外的來源中。
極性脂質通常分為磷脂及神經鞘脂類(包括神經節苷脂),其為具有疏水尾端及親水頭部基的兩親分子(amphiphilic molecule)。甘油磷脂是由其上兩脂肪酸的位置sn-1及sn-2被酯化的甘油骨架所組成。該些脂肪酸比乳中的三酸甘油酯部分更不飽合。具有不同有機基團(膽鹼、絲胺酸、乙醇胺等)之磷酸鹽殘基可在第三個羥基上被連接。一般而言,位於sn-1位置上的脂肪酸鏈比
位於Sn-2位置上的脂肪酸鏈更飽合。溶血磷脂只含有一個醯基,主要位於sn-1位置。頭部基維持類似。神經鞘脂類之特性結構單元為含有二或三個羥基的長鏈(12至22個碳原子)脂族胺之鞘脂基。含有18個碳原子、二個羥基及一個雙鍵的神經胺醇(d18:1)為最哺乳動物神經鞘脂類中最廣泛的鞘脂基。通常當此鞘脂基的胺基與飽和脂肪酸連接時,形成神經醯胺。有機磷酸鹽基可被鍵結於此神經醯胺單元上以形成神經磷脂(如,以神經鞘磷脂為例的磷膽鹼)或鍵結於糖類以形成神經糖脂(糖苷基神經醯胺)。如葡萄糖苷基神經醯胺或半乳糖苷基神經醯胺的單糖苷基神經醯胺通常表示為腦苷脂(cerebroside),而具有末端半乳糖胺殘基的三及四葡萄糖苷基神經醯胺表示為紅血球苷脂(globoside)。最後,除了葡萄糖、半乳糖及半乳糖胺之外,神經節苷脂為含有一或多個唾液酸基的高複雜度的寡糖苷基神經醯胺(oligoglycosylceramide)。
「完整營養」意指可用作為營養唯一來源的組成物,其提供所有每日基本所需量之與蛋白質、碳水化合物及脂質結合的維生素、礦物質、及/或微量元素。事實上,「完整營養」描述了提供所需之足夠量的碳水化合物、脂質、必需脂肪酸、蛋白質、必需胺基酸、條件性必需胺基酸、維生素、礦物質及能量的營養組成物,以支持個體的正常生長及發育。
因此,顧名思義,對於早產兒來說營養組成
物為在質與量上可提供早產兒生長所需之足夠量之碳水化合物、脂質、必需脂肪酸、蛋白質、必需胺基酸、條件性必需胺基酸、維生素、礦物質及能量的「完整營養」。
顧名思義,對於足月嬰兒來說營養組成物為在質與量上可提供足月嬰兒生長所需之足夠量之碳水化合物、脂質、必需脂肪酸、蛋白質、必需胺基酸、條件性必需胺基酸、維生素、礦物質及能量的「完整營養」。
顧名思義,對於孩童來說營養組成物為在質與量上可提供孩童生長所需之足夠量之碳水化合物、脂質、必需脂肪酸、蛋白質、必需胺基酸、條件性必需胺基酸、維生素、礦物質及能量的「完整營養」。
當用於營養成分時,「必需」一詞意指無法由體內合成足以正常生長及維持健康的任何營養成分,而因此必需由飲食供給。當「條件性必需」一詞用於營養成分時,意指當發生體內無法得到足夠量之前驅化合物以供內源性合成的條件下,營養成分必需在藉由飲食供給。
「益生菌」意指對宿主健康發揮有益的影響之具有低或不具有致病性的微生物。
「失活益生菌」一詞意指其中所引用之益生菌的代謝活性或繁殖能力被降低或破壞之益生菌。然而,「失活益生菌」在細胞等級上仍保有其細胞結構或與細胞相關之其他結構,例如胞外多醣體及其生物醣蛋白與DNA/RNA結構之至少一部分。如本文中所使用,「失活」一詞與「無活性」同義。
「益菌生」意指藉由選擇性刺激消化道中可改善宿主的健康的一或有限數量之細菌的生長及/或活性進而有益地影響宿主的不易消化的食物成分。
若組分為存在於其他組分的組成物或組成物的成分中(即,自然存在於其他組分中),其被稱為「固有性」、「內源性」、或存在於「內源性來源」。反之,「外源性」意指有意包括於本揭示本身之營養組成物中的組分,而不是其他組分的元素。舉例來說,「固有性肌醇」、「內源性肌醇」或「來自內源性來源的肌醇」各者意指不經添加而存在於組成物中的肌醇,而非存在於其他組分或組成物的成分;肌醇為自然存在於其他組分中。「外源性」肌醇為有意包括於本揭示本身的營養組成物的肌醇,而非其他組分的元素。
「支鏈脂肪酸(BCFA)」意指含有自碳鏈分支出碳組分之脂肪酸。典型上支鏈為烷基支鏈、尤其是甲基基團、亦已知有乙基及丙基支鏈。相較於等量之支鏈脂肪酸,添加甲基支鏈降低其熔點。此包括在碳鏈中具有偶數之碳原子的支鏈脂肪酸。此等之範例可為十四烷酸、十六烷酸之異構物。
「奇數及支鏈脂肪酸(OBCFA)」為BCFA之子集,其具有奇數碳原子且在碳鏈上具有一或更多烷基支鏈。已在牛乳中發現主要的奇數及支鏈脂肪酸包括,但不限於,十四烷酸、十五烷酸、十六烷酸及十七烷酸之異構物。對於本揭示之目的,「BCFA」一詞包括支鏈脂肪
酸及奇數及支鏈脂肪酸兩者。
「磷脂」意指含有二甘油酯、磷酸基團及簡單有機分子之有機分子。磷脂的範例包括,但不限於,磷脂酸、磷脂醯乙醇胺、卵磷脂、磷脂質絲胺酸、磷脂酸肌醇、磷脂酸肌醇磷酸、磷脂酸肌醇二磷酸及磷脂酸肌醇三磷酸、神經醯胺磷酸膽鹼、神經醯胺磷酸乙醇胺及神經醯胺磷酸甘油。此定義進一步包括神經鞘脂類,諸如神經鞘磷脂。鞘糖脂為MFGM之微量成分,且由腦苷脂(含有不帶電糖類之中性醣化神經磷脂)及神經節苷脂。神經節苷脂為酸化的醣化神經磷脂,其包含唾液酸(N-乙醯神經氨酸(NANA))作為其碳水化合物基團之部分。源自不同合成路徑之各種不同類型的神經節苷脂包括GM3、GM2、GM1a、GD1a、GD3、GD2、GD1b、GT1b及GQ1b(Fujiwara et al.,2012)。乳中主要的神經節苷脂為GM3及GD3(Pan & Izumi,1999)。不同類型的神經節苷脂之其碳水化合物側鏈的本質及長度及附接至該分子的唾液酸的數量也不同。
「植物營養素」意指植物中自然存在的化學化合物。植物營養素可包括於任何源自植物的物質或萃取物。「植物營養素」一詞涵括由植物所製造之數大類化合物,諸如,例如多酚類化合物、花青素、原花青素及黃烷-3-醇(即,兒茶素、表兒茶素)與源自例如水果、種子或茶葉萃取物。此外,植物營養素一詞包括包括所有類胡蘿蔔素、植物固醇、硫醇、及其他源自植物的化合物。再
者,如專業人士所了解的,除了蛋白質、纖維素或其他源自植物的組分之外,植物萃取物可包括植物營養素,諸如多酚。因此,例如蘋果或葡萄籽萃取物,除了其他源自植物的物質之外,可包括有益的植物營養素組分,諸如多酚。
「β-葡聚糖」意指所有的β-葡聚糖,包括特定類型的β-葡聚糖,諸如β-1,3-葡聚糖或β-1,3;1,6-葡聚糖。此外,β-1,3;1,6-葡聚糖為β-1,3-葡聚糖的一種類型。因此,「β-1,3-葡聚糖」一詞包括β-1,3;1,6-葡聚糖。
「果膠」意指任何自然存在的寡糖或多糖,其包含可發現於所有植物的細胞壁的半乳糖醛酸。在本領域已知不同品種及等級的果膠具有不同的物理及化物性質。事實上,果膠的結構在植物間、組織間甚至是在單一細胞壁內可能明顯不同。一般來說,果膠是由帶負電的酸性糖類(半乳糖醛酸)製成,而某些酸性基團為甲酯基團的形式。果膠的酯化程度為計算附接至以甲醇酯化的吡喃半乳糖苷基醛酸(galactopyranosyluronic acid)之羧基基團之百分比。
酯化程度小於50%(即,小於50%之羧酸基團被甲基化成甲酯基團)的果酸被分類為低酯(low-ester)、低甲氧基、或低甲基化(「LM」)果酸,而酯化程度為50%或更大(即,大於50%的羧酸基團被甲基化)的果酸被分類為高酯(high-ester)、高甲氧基或高甲基化(「HM」)果酸。極低(「VL」)果膠(低甲基
化果膠的子集)的酯化程度低於約15%。
如本文中所使用,「來自非人來源的乳鐵蛋白」意指由人乳以外的來源製造或獲得的乳鐵蛋白。例如,本揭示中所使用之乳鐵蛋白包括由基因改造的生物製造的人類乳鐵蛋白以及非人乳鐵蛋白。如本文中所使用的「生物體」一詞意指連續的生物系統,諸如動物、植物、真菌或微生物。
如本文中所使用,「非人乳鐵蛋白」意指具有與人類乳鐵蛋白的胺基酸序列不同的胺基酸序列。
「致病原」意指造成疾病狀態或病理症候群之生物體。致病原之範例可包括細菌、病毒、寄生蟲、真菌、微生物或其組合。
「調控」意指發揮修飾、控制及/或調節影響。在一些實施例中,「調控」一詞意指對特定組分活性或影響的程度/量呈現增加或刺激的效果。在其他實施例中,「調控」意指對特定組分活性或影響的程度/量呈現降低或抑制的效果。
除非另外說明,本文中所使用的所有百分比、份量及比例為以總配方之重量計。
「每日」施予所指明之所有量為可在24小時期間區間施以一單位劑量、以單一份或以二或更多劑量或份來遞送。
本揭示之營養組成物實質上可能無任何本文中所述之可選的或選定之成分,前提是剩餘之組成物仍含
有本文中所述之所有所需之成分或特徵。除非特別說明,在此上下文中「實質上無」一詞意指所選定之組成物可能含有少於可選之成分的功能性量,通常少於0.1重量%,以及包括此可選或選定成分的0重量%。
針對本揭示之特異的特徵或限制的所有參考將包括對應之複數個特徵或限制,反之亦然,除非另外說明或清楚指示與其參考之上下文相反。
如本文中所使用之方法或處理步驟之所有組合可以任何順序進行,除非另外說明或清楚指示與其參考組合之上下文相反。
本揭示之方法及組成物(包括其組分)可包含、組成以、或基本上由必需元件及本文中所述之實施例的限制、以及任何額外或可選的成分、組分或本文所述之限制或其他可用於營養組成物所組成。
如本文中所使用,「約」一詞應建立以意指任何範圍之端點所指定之兩數值。對於範圍之任何參考應視為對該範圍內任何子集提供支援。
本揭示為導向藉由對小兒個體(通常藉由餵食)施予本文中揭示之營養組成物而用於促進小兒個體的認知發展的方法。本揭示之營養組成物藉此支援且改善神經健康及發育。
本揭示之營養組成物包括強化乳製品,諸如eWPC。如同所示,強化乳製品可藉由任何數量之分餾技術製造。這些技術包括但不限於融化分餾、有機溶劑分
餾、超臨界流體分餾,及其任何變化及組合。或者,eWPC為可市售獲得,包括商品名Lacprodan MFGM-10。另外適合之強化乳製品為可市售獲得之商品名Lacprodan PL-20。Lacprodan MFGM-10及Lacprodan PL-20可自丹麥Viby的Arla Food Ingredients購得。就強化乳製品的添加物來說,嬰兒配方奶粉及其他幼兒營養組成物的脂質組成物可更接近於人乳的脂質組成物。舉例來說,在嬰兒配方奶粉的範例中,計算包括Lacprodan MFGM-10或Lacprodan PL-20的磷脂(mg/L)及神經節苷脂(mg/L)之理論值如表1所示:
PL:磷脂;SM:神經鞘磷脂;PE:磷脂醯乙醇胺;PC:磷脂醯膽鹼;PI:磷脂醯肌醇;PS:磷脂醯絲胺酸;GD3:神經節苷脂GD3。
在一些實施例中,強化乳製品為以每公升約0.5克(g/L)至約10g/L包括於本揭示之營養組成物中;在其他實施例中,強化乳製品以約1g/L至約9g/L的濃度存在。在其他實施例中,強化乳製品以約3g/L至約8g/L的濃度之營養組成物存在。或者,在特定實施例中,
強化乳製品為以每100Kcal(g/100Kcal)約0.06克至約1.5g/100Kcal的濃度包括於本揭示之營養組成物中;在其他實施例中,強化乳製品為以約0.3g/L至約1.4g/L的濃度存在。在另外其他實施例中,強化乳製品為以約0.4g/100Kcal至約1g/100Kcal的濃度之營養組成物存在。
本文中所揭示之營養組成物中之總磷脂(即,若有使用,包括來自強化乳製品之磷脂以及其他組分,但不包括來自植物來源之磷脂,諸如大豆卵磷脂)為在約50mg/L至約2000mg/L的範圍內;在一些實施例中,其為約100mg/L至約1000mg/L,或約150mg/L至約550mg/L。在特定實施例中,MFGM組分亦提供約10mg/L至約200mg/L範圍之神經鞘磷脂;在其他實施例中,其為約30mg/L至約150mg/L,或約50mg/L至約140mg/L。且,在一些實施例中,強化乳製品亦可提供以約2mg/L至約40mg/L範圍存在的神經節苷脂,在其他實施例中約6mg/L至約35mg/L。在其他實施例中,神經節苷脂為以約9mg/L至約30mg/L的範圍存在。在一些實施例中,營養組成物中的總磷脂(仍不包括來自植物來源之磷脂,諸如大豆卵磷脂)為約6mg/100Kcal至約300mg/100Kcal的範圍;在一些實施例中其為約12mg/100Kcal至約150mg/100Kcal,或約18mg/100Kcal至約85mg/100Kcal。在特定實施例中,強化乳製品亦提供約1mg/100Kcal至約30mg/100Kcal範圍的神經鞘磷脂;在其他實施例中,其為約3.5mg/100Kcal至約24
mg/100Kcal,或約6mg/100Kcal至約21mg/100Kcal。且,神經節苷脂可以約0.25mg/100Kcal至約6mg/100Kcal之範圍存在,或者,在其他實施例中約0.7mg/100Kcal至約5.2mg/100Kcal。在其他實施例中,神經節苷脂為以1.1mg/100Kcal至約4.5mg/100Kcal的範圍存在。
在特定實施例中,除了強化乳製品及其組分之外,營養組成物包括強化脂質部分,其可提供飽合脂肪酸、單不飽合脂肪酸、多不飽合脂肪酸、OBCFA、BCFA、CLA、膽固醇、磷脂來源至營養組成物。
此外,在一些實施例中,強化脂質部分可包括月桂酸。月桂酸又稱為十二烷酸,為具有12個碳原子之鏈的飽合脂肪酸,且近期在人乳中發現咸信為抗病毒及抗菌物質之一。在不受到理論所約束,咸信當攝入強化脂質部分時,口腔舌脂解酶及胰脂酶將三酸甘油酯水解為包括單月桂酸及自由月桂酸之甘油酯的混合物,其在一些實施例中以80mg/100ml至800mg/100ml存在。單月桂基的濃度可在20mg/100ml至300mg/100ml的範圍中。
在一些實施例中,強化脂質部分亦可包含OBCFA。在特定實施例中,OBCFA可以約0.3g/100Kcal至約6.1g/100Kcal的量存在。在其他實施例中,OBCFA可以約2.2g/100Kcal至約4.3g/100Kcal的量存在。在又一實施例中,OBCFA可以約3.5g/100Kcal至約5.7g/100Kcal的量存在。
在一些實施例中,強化脂質部分可包含BCFA。在一些實施例中,BCFA以約0.2g/100Kcal至約5.82g/100Kcal的濃度存在。在另一實施例中,BCFA以約2.3g/100Kcal至約4.2g/100Kcal的量存在。在又另一實施例中,BCFA以約4.2g/100Kcal至約5.82g/100Kcal存在。
在一些實施例中強化脂質部分可包括CLA。CLA可以約0.4g/100Kcal至約2.5g/100Kcal的濃度存在。在其他實施例中CLA可以約0.8g/100Kcal至約1.2g/100Kcal存在。在另一實施例中CLA可以約1.2g/100Kcal至約2.3g/100Kcal存在。在強化脂質部分中發現之CLA的範例包括,但不限於,順-9,反-11CLA、反-10,順-12CLA、順-9,反-12十八碳二烯酸,及其混合物。
本揭示之營養組成物亦可含有LCPUFA的來源;尤其是包含DHA之LCPUFA的來源。其他適合之LCPUFA包括,但不限於α-亞麻油酸、γ-亞麻油酸、亞麻油酸、次亞麻油酸、二十碳五烯酸(EPA)及ARA。
在一實施例中,尤其是若營養組成物為嬰兒配方奶粉,則營養組成物補充DHA及ARA兩者。在此實施例中,ARA:DHA之重量比可介於約1:3及約9:1之間。在一特定實施例中,ARA:DHA之比為約1:2至約4:1。
營養組成物中長鏈多不飽合脂肪酸的量有利地為至少約5mg/100Kcal,且在一些實施例中可為約24
mg/100Kcal至約90mg/100Kcal變化,更佳地約26mg/100Kcal至約72mg/100Kcal變化。在特定實施例中,LCPUFA以約29mg/100Kcal至約72mg/100Kcal之濃度存在。
營養組成物可使用本領域已知之標準技術補充含有DHA及/或ARA之油。舉例來說,DHA及ARA可藉由取代等量之油(諸如高油酸葵花油,通常存在於組成物中)而被添加至組成物。如另一範例,含有DHA及ARA的油可藉由取代等量剩餘之整體脂肪摻合物(通常存在於無DHA及ARA之組成物中)而添加至組成物中。
若有使用,DHA及/或ARA之來源可為本領域中已知之來源,諸如水產油(marine oil)、魚油、單細胞油、蛋黃脂質及腦脂質。在一些實施例中,DHA及ARA為源自單細胞Martek油、DHASCO®及ARASCO®或其變異物。DHA及ARA可為自然形式,前提為LCPUFA來源之剩餘部分不會對嬰兒造成任何實質有害影響。另外,DHA及ARA可以精製的形式來使用。
在一實施例中,DHA及ARA之來源為如美國專利第5,374,567;5,550,156及5,397,591所教示,該等揭示藉由引用其全文而併入本文中。然而,本揭示並不僅限於此等油。
在特定實施例中,營養組成物亦含有一或多種益菌生(又稱為益菌生組分)。益菌生發揮健康益處,其可包括,但不限於選擇性刺激一或有限量之腸道益菌之
生長及/或活性、刺激攝入的益生菌微生物之生長及/或活性、選擇性降低腸道致病原及對腸道短鏈脂肪酸輪廓有益之影響。不論此新來源為現在已知的或往後發展的,此種益菌生可為自然存在、合成、或透過有機體及/或植物之基因調變而發展出。在本揭示中可用的益菌生可包括寡糖、多糖,而其他益菌生包含果糖、木糖、大豆、半乳糖、葡萄糖及甘露糖。
更具體地,本揭示中可用的益菌生可包括多糖類(PDX)、多糖類粉末、乳酮糖(lactulose)、乳果糖(lactosucrose)、棉子糖、葡聚寡糖(gluco-oligosaccharide)、菊糖(inulin)、果寡糖(fructo-oligosaccharide,FOS)、異麥芽寡糖(isomalto-oligosaccharide)、大豆寡糖(soybean oligosaccharide)、乳果糖、木寡糖(xylo-oligosaccharide,XOS)、殼寡糖(chito-oligosaccharide)、甘露寡糖(manno-oligosaccharide)、阿拉伯寡糖(aribino-oligosaccharide)、唾液寡糖(siallyl-oligosaccharide)、岩藻寡糖(fuco-oligosaccharide)、半乳寡糖(galacto-oligosaccharide,GOS)及龍膽寡糖(gentio-oligosaccharide)。
在一實施例中,存在於營養組成物中的益菌生之總量可為組成物之約1.0g/L至約10.0g/L。更佳地,存在於營養組成物中的益菌生之總量可為組成物之約2.0g/L至約8.0g/L。在一些實施例中,存在於營養組成物中的益菌生之總量可為約0.01g/100Kcal至約1.5
g/100Kcal。在特定實施例中,存在於營養組成物中的益菌生之總量可為約0.15g/100Kcal至約1.5g/100Kcal。此外,營養組成物可包含包含PDX之益菌生組分。在一些實施例中,益菌生組分包含至少20% w/w PDX、GOS或其混合物。
在一實施例中,營養組成物中之PDX的量可在約0.015g/100Kcal至約1.5g/100Kcal之範圍內。在另一實施例中,多糖類之量介於0.2g/100Kcal至約0.6g/100Kcal之間的範圍。在一些實施例中,PDX可以足以提供介於約1.0g/L及10.0g/L之間的量被包括在營養組成物中。在另一實施例中,營養組成物含有介於約2.0g/L及8.0g/L之間之PDX量。且在其他實施例中,營養組成物中之PDX量可為約0.05g/100Kcal至約1.5g/100Kcal。在另一實施例中,存在於營養組成物中之PDX為約0.05g/100Kcal至約1.3g/100Kcal之濃度。
在一些實施例中益菌生組分亦包含GOS。在一實施例中,營養組成物中GOS的量可為約0.015g/100Kcal至約1.0g/100Kcal。在另一實施例中,營養組成物中GOS的量可為約0.2g/100Kcal至約0.5g/100Kcal。
在本揭示之特定實施例中,PDX與GOS一起施予。
在特定實施例中,GOS及PDX以至少約0.015g/100Kcal或約0.015g/100Kcal至約1.5g/100Kcal之總量被補充至營養組成物中。在一些實施例中,營
養組成物可包含總量約0.1至約1.5g/100Kcal之GOS及PDX。
如所註記的,在一些實施例中,本揭示之營養組成物除了強化乳製品、長鏈多不飽合脂肪酸及益菌生之外,包括唾液酸、短鏈脂肪酸及/或維生素B12。
所使用之唾液酸(SA)一詞通常意指神經胺酸之衍生物家族。N-乙醯神經胺酸(Neu5Ac)及N-羥基乙醯神經胺酸(Neu5Gc)為自然中最常見的SA形式,尤其是人類及牛的乳中的Neu5Ac。由於SA參與諸如神經細胞附著分子(NCAM)及脂質(例如,神經節苷脂)之腦特異性蛋白,哺乳動物腦組織含有最高濃度之SA。SA被視為在神經發育及功能、學習、認知及一生的記憶中扮演重要角色。在人乳中,SA以自由及與寡糖、蛋白質及脂質接合的形式存在。人乳中的SA含量隨著哺乳期而變化,其在初乳中濃度最高。然而,相較於在人乳中主要與自由寡糖接合之SA,牛乳中的大多數SA與蛋白質接合。如本文中藉由引用而併入之各揭示之美國專利第7,867,541及7,951,410號所討論,唾液酸能以原樣併入所揭示之營養組成物,或其可藉由併入具有強化唾液酸含量之酪蛋白糖巨肽(cGMP)而提供。
當唾液酸存在時可以約100mg/L至約800mg/L的濃度併入本揭示之營養組成物中,包括來自強化乳製品與外源唾液酸之固有唾液酸及來自諸如cGMP之唾液酸兩者。在一些實施例中,唾液酸以約120mg/L至約
600mg/L的濃度存在;在其他實施例中為約140mg/L至約500mg/L的濃度。在特定實施例中,唾液酸可以約1mg/100Kcal至約120mg/100Kcal之量存在。在其他實施例中唾液酸可以約14mg/100Kcal至約90mg/100Kcal之量存在。在又另外的實施例中,唾液酸可以約15mg/100Kcal至約75mg/100Kcal之量存在。
在一些實施例中營養組成物含有短鏈脂肪酸(即,具有6個碳或更短之鏈長度之脂肪酸)。短鏈脂肪酸可以約2mg/100Kcal至約200mg/100Kcal的濃度存在。在特定實施例中,短鏈脂肪酸可以約5mg/100Kcal至約150mg/100Kcal存在。在其他實施例中短鏈脂肪酸可以約8mg/100Kcal至約100mg/100Kcal存在。適用於列入短鏈脂肪酸之範例包括乙酸、丙酸、丁酸、異丁酸、戊酸、異戊酸、己酸及/或其組合,其中丁酸及己酸較佳。在一些實施例中,短鏈脂肪酸(尤其是丁酸及己酸)對LCPUFA之比在1:10至10:1的範圍內。
維生素B12(鈷胺素(cobalamin))只由細菌產生,而人類依賴來自膳食來源之B12營養攝取。在嬰兒中,嚴重的B12不足將造成神經病徵諸如易怒、厭食、冷漠及發育衰退(development regression)。然而未完全了解,此機制可能與神經的延遲髓鞘化(myelination)或去髓鞘化(demyelination)有關。運鈷胺素蛋白(haptocorrin)被發現在人乳中作為B12的結合蛋白。因此運鈷胺素蛋白可能有利於維生素B12之攝入。關於以牛
乳為基之嬰兒配方奶粉中的運鈷胺素蛋白資訊較少。但是,維生素B12在酸性條件下諸如在胃中為不穩定的。然而,已發現B12與乳鐵蛋白的複合物之穩定性被改善。因此,在特定實施例中,維生素B12具備乳鐵蛋白,或與乳鐵蛋白相關,其中維生素B12以約0.018mcg/100Kcal至約1.5mcg/100Kcal之範圍存在;在其他實施例中,維生素B12的濃度為約0.045mcg/100Kcal至約1.4mcg/100Kcal,或甚至約0.15mcg/100Kcal至約1.2mcg/100Kcal。
此外,在一些實施例中,乳鐵蛋白亦包括於本揭示之營養組成物中。乳鐵蛋白為含有1至4個聚糖(取決於物種)約80kD的單鏈多肽。不同物種之乳鐵蛋白的3D結構非常相似,但不完全一樣。各個乳鐵蛋白包含兩個同源性球葉(homologous lobe),稱為N-球葉及C-球葉,分別指分子的N端及C端部分。各個球葉進一步由兩個子球葉或域組成,其形成鐵離子(Fe3+)可與(重)碳酸鹽陰離子協同合作而緊密結合的裂隙。這些域分別稱為N1、N2、C1及C2。乳鐵蛋白的N端具有強大的陽離子胜肽區,其回應於數種重要結合特性。乳鐵蛋白具有非常高的等電點(約pI 9)且其陽離子本質上在對細菌、病毒及真菌致病原的抵抗上扮演主要角色。有數種群集之具有乳鐵蛋白N端區之陽離子胺基酸殘基調控乳鐵蛋白對抗廣大的微生物之生物活性。舉例來說,對乳鐵蛋白的與鐵無關生物活性的關鍵為人類乳鐵蛋白N端殘基1-
47(牛乳鐵蛋白的1-48)。在人類乳鐵蛋白中,殘基2至5(RRRR)及28至31(RKVR)為N端中富含精胺酸的陽離子域,對乳鐵蛋白的抗菌活性尤為關鍵。在牛乳鐵蛋白中發現類似的N端區(殘基17至42;FKCRRWQWRMKKLGAPSITCVRRAFA)。
來自不同的宿主物種的乳鐵蛋白,其胺基酸序列可能不同,雖然通常在內球葉末端區帶正電荷的胺基酸而具有相對高的等電點。用於本揭示中之適當的非人乳鐵蛋白包括,但不限於那些與人類乳鐵蛋白胺基酸序列有至少48%同源者。舉例來說,牛乳鐵蛋白(「bLF」)具有與人類乳鐵蛋白約70%序列同源之胺基酸組成物。在一些實施例中,非人乳鐵蛋白具有與人類乳鐵蛋白至少55%同源,且在一些實施例中,至少65%同源。本揭示中使用可接受之非人乳鐵蛋白包括,但不限於bLF、豬乳鐵蛋白、馬乳鐵蛋白、水牛乳鐵蛋白、山羊乳鐵蛋白、鼠乳鐵蛋白及駱駝乳鐵蛋白。
在一實施例中,乳鐵蛋白以至少約15mg/100Kcal的量存在於營養組成物中。在特定實施例中,營養組成物可包括每100Kcal介於約15及約300mg之間的乳鐵蛋白。在另一實施例中,其營養組成物為嬰兒配方奶粉,營養組成物每100Kcal可包含約60mg至約150mg的乳鐵蛋白的量的乳鐵蛋白;又另一實施例中,營養組成物每100Kcal可包含約60mg至約120mg乳鐵蛋白。在一些實施例中,當營養組成物為液體,其可
包括約0.3g/L至約18g/L之組成物的量。在營養組成物中提供完整營養,乳鐵蛋白可以約0.3g/L至約4.4g/L的量存在。在特定實施例中,營養組成物可包含介於約0.3g/L及約2.5g/L。在一些實施例中,營養組成物包括每公升配方介於約0.4及約1.5 gram之間的乳鐵蛋白。
本揭示中使用的乳鐵蛋白可為例如自非人動物之乳分離或由基因改造生物生產。舉例來說,在美國專利第4,791,193號中,將其藉由在本文中引用其全文而併入,Okonogi等人揭示用於製造高純度牛乳鐵蛋白的方法。一般來說,所揭示之方法包括三個步驟。首先,將生乳原料與弱酸陽離子交換器接觸以吸附乳鐵蛋白,接著進行第二步驟清洗以移除未吸附之物質。接著解吸附步驟移除乳鐵蛋白以製造純化的牛乳鐵蛋白。其他方法可包括如美國專利第7,368,141、5,849,885、5,919,913及5,861,491號中所述之步驟,將其所揭示者皆藉由引用其全文而併入。
在特定實施例中,本揭示中所利用之乳鐵蛋白可藉由用於從乳源分離蛋白質的膨脹床吸附(EBA)法來提供。EBA(有時亦稱為穩定流體床吸附)為用於自乳源分離乳蛋白質(諸如乳鐵蛋白)的方法,包含建立一膨脹床吸附管柱,管柱包含顆粒狀基質,將乳源施加至基質,並以包含約0.3至約2.0M氯化鈉的沖提緩衝液(elution buffer)將乳鐵蛋白自基質沖提出。任何哺乳類動物乳源皆可用於本方法,雖然在特定實施例中乳源為牛
乳源。在一些實施例中,乳源包含全脂乳、低脂乳、脫脂乳、乳清、酪蛋白或其混合物。
在特定實施例中,目標蛋白質為乳鐵蛋白,雖然其他乳蛋白質(諸如乳過氧化酶或乳白蛋白)也可能被分離出來。在一些實施例中,本方法包含建立包含顆粒狀基質的膨脹床吸附管柱之步驟,將乳源施加至基質,並以約0.3至約2.0M氯化鈉自基質將乳鐵蛋白沖提出。在其他實施例中,以約0.5至約1.0M氯化鈉將乳鐵蛋白沖提出,而更進一步實施例,以約0.7至約0.9M氯化鈉將乳鐵蛋白沖提出。
膨脹床吸附管柱在本領域中為已知的,諸如美國專利第7,812,138、6,620,326及6,977,046號,將其所揭示者藉由在本文中引用而併入。在一些實施例中,將乳源施加至膨脹模式的管柱中,並在膨脹或者在填充模式中進行沖提。在特定實施例中,沖提是在膨脹模式中進行。舉例來說,膨脹模式中的膨脹率可為約1至約3、或約1.3至約1.7。EBA技術進一步描述於將藉由引用其全文而併入之國際公開申請案第WO 92/00799、WO 02/18237、WO 97/17132號。
乳鐵蛋白的等電點為約8.9。早先分離乳鐵蛋白的EBA法使用200mM氫氧化鈉作為沖提緩衝液。因此,系統之pH上升至超過12,且乳鐵蛋白的結構及生物活性將由於不可逆的結構改變而受損。現今已發現在自EBA基質分離乳鐵蛋白時,可使用氯化鈉溶液作為沖提緩
衝液。在特定實施例中,氯化鈉的濃度約0.3M至約2.0M。在其他實施例中,乳鐵蛋白沖提緩衝液的氯化鈉濃度約0.3M至約1.5M,或約0.5M至約1.0M。
在一些實施例中,本揭示之營養組成物亦可包含至少一蛋白質或蛋白質等同物來源(除了乳鐵蛋白及強化乳製品蛋白質以外),其可在本領域中任意使用,如脫脂乳、乳清蛋白、酪蛋白、大豆蛋白、水解蛋白質、胺基酸等等。實施本揭示可使用的牛乳蛋白來源包括,但不限於乳蛋白粉、乳蛋白濃縮物、乳蛋白分離物、脫脂乳固形物、脫脂乳、脫脂奶粉、乳清蛋白、乳清蛋白分離物、乳清蛋白濃縮物、甜乳清、酸乳清、酪蛋白、酸性酪蛋白、酪蛋白鹽(如,酪蛋白鈉、酪蛋白鈣鈉、酪蛋白鈣)及其任何之組合。
在一些實施例中,營養組成物之蛋白質被提供作為完整蛋白質。在其他實施例中,蛋白質被提供為完整蛋白質及水解蛋白質兩者之組合。在特定實施例中,蛋白質可為部分水解或大量水解。在其他實施例中,蛋白質等同物來源包含胺基酸。在更另一實施例中,蛋白質來源可以含麩醯胺的胜肽來補充。在另一實施例中,蛋白質組分包含大量水解蛋白質。在又一實施例中,營養組成物的蛋白質組分基本上由大量水解蛋白質組成,用以使食物過敏的發生最小化。在更另一實施例中,蛋白質來源可以含麩醯胺的胜肽來補充。
因此,在一些實施例中,營養組成物的蛋白
質組分包含部分或大量水解蛋白質,諸如來自牛乳的蛋白質。水解蛋白質可以酵素處理以降解造成不良症狀的一些或大部分蛋白質,以達到減少過敏反應、不耐症及過敏反應。此外,蛋白質可藉由本領域中已知之方法水解。
「蛋白質水解產物」或「水解蛋白質」一詞在本用中可交換使用且意指經水解的蛋白質,其中水解的程度可為約2%至約80%、或3%至20%、或20%至80%、或約30%至約80%或甚至約40%至約60%。
當蛋白質的胜肽鍵藉由酵素水解而打斷時,每一胜肽鍵斷裂就釋放出一個胺基,使得胺基氮增加。應注意的是,即使非經水解的蛋白質仍含有一些暴露的胺基。相較於非經水解的蛋白質,由非經水解的蛋白質形成之經水解的蛋白質亦將具有不同的分子量分佈。經水解的蛋白質之功能及營養特性可被不同尺寸的胜肽影響。分子量輪廓為通常藉由列出特定範圍分子量(以道爾吞為單位)片段(例如,2,000至5,000道爾吞、大於5,000道爾吞)的重量百分比。
在特定實施例中,營養組成物含有自由胺基酸作為蛋白質等同物來源。在此實施例中,胺基酸可包含,但不限於組胺酸、異白胺酸、白胺酸、離胺酸、甲硫胺酸、半胱胺酸、苯丙胺酸、酪胺酸、蘇胺酸、色胺酸、纈胺酸、丙胺酸、精胺酸、天門冬醯胺、天門冬胺酸、麩胺酸、麩醯胺、甘胺酸、脯胺酸、絲胺酸、肉鹼、牛磺酸及其混合物。在一些實施例中胺基酸可為支鏈胺基酸。在
其他實施例中,小胺基酸胜肽可包括作為營養組成物的蛋白質組分。此種小胺基酸胜肽可為自然存在或經合成。營養組成物中的自由胺基酸量可在約1至約5g/100Kcal變化。在一實施例中,100%自由胺基酸的分子量小於500道爾吞。在此實施例中,此營養配方可為低過敏性。
在一實施例中,蛋白質來源包含約40%至約85%乳清蛋白及約15%至約60%酪蛋白。
在一些實施例中,營養組成物包含不大於7g/100Kcal、且在特定實施例中每100Kcal介於約1g及約7g之蛋白質及/或蛋白質等同物來源。在其他實施例中,營養組成物每100Kcal包含介於約1.5g及約4.5g之蛋白質或蛋白質等同物。
在一些實施例中,營養組成物包含至少一碳水化合物。可任用於本領域之碳水化合物來源,如乳糖、葡萄糖、果糖、玉米糖漿固形物、麥芽糊精、蔗糖、澱粉、米漿固形物等等。營養組成物中額外的碳水化合物組分的量典型地大於5g/100Kcal;在一些實施例中,其可在介於約5g及約25g/100Kcal之間變化。在一些實施例中,碳水化合物的量係介於約6g及約22g/100Kcal之間。在其他實施例中,碳水化合物的量係介於約9g及約14g/100Kcal之間。在一些實施例中,較佳為玉米糖漿及/或麥芽糊精。此外,由於水解的、部分水解的及/或大量水解的碳水化合物容易消化,該等為較希望包括於營養組成物中。具體來說,經水解的碳水化合物較不易含有過
敏抗原表位。
適用於本文中的碳水化合物材料之非限制性範例包括經水解的或完整的、天然的或經化學修飾的、以糯性或非糯性形式之來自玉米、木薯、米或馬鈴薯的澱粉來源。適當的碳水化合物之非限制性範例包括各種經水解澱粉,其特徵在於經水解玉粉澱粉、麥芽糊精、麥芽糖、玉米糖漿、右旋糖、玉米糖漿固形物、葡萄糖及各種其他葡萄糖聚合物及其組合物。其他適當的碳水化合物之非限制性範例包括那些通常指為蔗糖、乳糖、果糖、高果糖玉米糖漿、不可消化寡糖諸如果寡糖及其組合。
在一特定實施例中,營養組成物之碳水化合物組分包含100%乳糖。在另一實施例中,額外的碳水化合物組分包含介於約0%及60%的乳糖。在另一實施例中,碳水化合物組分包含介於約15%及55%的乳糖。在又一實施例中,碳水化合物組分包含介於約15%及30%的乳糖。在這些實施例中,碳水化合物的剩餘來源可為本領域中已知的任意碳水化合物。在一實施例中,碳水化合物組分包含約25%乳糖及約75%玉米糖漿固形物。
在一些實施例中,碳水化合物包含至少一澱粉或澱粉組分。澱粉是由兩個不同聚合物片段組成的碳水化合物:直鏈澱粉(amylose)及支鏈澱粉(amylopectin)。直鏈澱粉為具有由α-1,4連接的葡萄糖單元的直鏈片段。支鏈澱粉具有與直鏈澱粉相同的結構,但有些葡萄糖單元以α-1,6連接結合而得到支鏈結構。澱
粉通常含有17至24%直鏈澱粉及76至83%支鏈澱粉。然而已開發出製造具有異常的直鏈澱粉對支鏈澱粉比例之特殊基因變異之植物。一些植物製造無直鏈澱粉的澱粉。這些突變體在胚乳及花粉中產生澱粉顆粒,其與碘染成紅色且含有將近100%的支鏈澱粉。在此種產生支鏈澱粉的植物主要為糯性玉米、糯性高梁、糯性馬鈴薯及糯米澱粉。
在熱、剪切及酸的環境下澱粉的性能可藉由物理或化學修飾而被修飾或改善。修飾通常藉由引入取代化學基團來達成。例如,於高溫或高剪應力的黏性可藉由與二或多官能基試劑(諸如氧氯化磷)交聯而增加或穩定。
在某些實例中,本揭示之營養組成物包含至少一經膠化或預膠化的澱粉。如本領域中所周知的,當聚合物分子與其長度的一部分交互作用以形成截留溶劑及/或溶質分子的網路時發生膠化作用(gelatinization)。此外,若使用果膠,當果膠分子失去一些由於共存溶質分子競爭水合之水合的水,則形成膠。影響膠化發生的因素包括pH、共存溶質的濃度、陽離子的濃度及類型、溫度及果膠濃度。值得注意的是,LM果膠只在二價陽離子(諸如鈣離子)的存在下凝膠。且在LM果膠之中,酯化度最低的該些者具有最高的凝膠溫度且最需要二價陽離子來交聯。
同時,澱粉的預膠化為預煮澱粉的方法,用以在冷水中製造水合物及膨脹的材料。接著將經預煮的澱
粉乾燥,例如藉由轉筒乾燥或噴霧乾燥。此外本揭示之澱粉可經化學修飾以進一步延伸其成品特性的範圍。本揭示之營養組成物可包括至少一預膠化澱粉。
天然澱粉顆粒無法溶解於水中,但當在水中加熱,當存在足夠熱能以克服澱粉分子的鍵結力時,天然澱粉顆粒開始膨脹。持續加熱下,顆粒膨脹至原始體積的數倍大。這些膨脹顆粒之間的磨擦為有助於澱粉糊黏性的主要因子。
本揭示之營養組成物可包含天然或經修飾之澱粉,諸如,例如糯性玉米澱粉、糯米澱粉、玉米澱粉、米澱粉、馬鈴薯澱粉、木薯澱粉、小麥澱粉或其任何混合物。一般來說,常見玉米澱粉包含約25%直鏈澱粉,而糯性玉粉澱粉幾乎由支鏈澱粉組成。同時,馬鈴薯澱粉通常包含約20%直鏈澱粉及80%支鏈澱粉,米澱粉包含相似的直鏈澱粉:支鏈澱粉比例,而糯米澱粉只包含約2%的直鏈澱粉。此外,木薯澱粉通常包含約15%至約18%直鏈澱粉,而小麥澱粉具有25%左右的直鏈澱粉含量,剩下的是支鏈澱粉。
在一些實施例中,營養組成物包含膠化及/或預膠化糯性玉粉澱粉。在其他實施例中,營養組成物包含膠化及/或預膠化木薯澱粉。亦可使用其他膠化或預膠化澱粉,諸如米澱粉或馬鈴薯澱粉。
此外,在一些實施例中,本揭示之營養組成物可包含至少一果膠來源。果膠來源可包含本領域中已知
之任何品種或等級的果膠。在一些實施例中,果膠具有小於50%之酯化程度且被分類為低甲基化(「LM」)果膠。在一些實施例中,果膠具有大於或等於50%之酯化程度且被分類為高酯或高甲基化(「HM」)果膠。在其他實施例中,果膠為非常低(「VL」)果膠,其具有小於約15%的酯化程度。此外,本揭示之營養組成物可包含LM果膠、HM果膠、VL果膠或其任何混合物。營養組成物可包括可溶於水的果膠。而且,如本領域中已知的,果膠溶液的溶解度與黏度與分子量、酯化程度、果膠製劑的濃度及pH與相對離子的存在有關。
此外,果膠具有形成膠的獨特能力。一般來說,在類似條件下,果膠的膠化程度、結膠溫度、及膠強度彼此成比例,且各者與果膠的分子量成正比且與酯化程度成反比。例如,當果膠的pH較低,羧基的離子化被抑制,且由於失去其電荷,醣類分子其全長不互相排斥。因此,多醣分子可聯合其長度的一部分以形成膠。然而具有愈高甲基化程度的果膠將在更高pH成膠,因為其在任何給定pH下具有較少羧酸根陰離子(J.N.Bemiller,An Introduction to Pectins:Structure and Properties,Chemistry and Function of Pectins;Chapter 1;1986)。
營養組成物可包含與果糖及/或膠化果糖一起膠化及/或預膠化的澱粉。然而不希望被任何其他理論所束縛,咸信果膠(諸如LM果膠,為大分子膠體)與澱粉顆粒的使用提供了加流體基質中的分子內部磨擦的協同效
應。果膠的羧基亦可與存在於營養組成物中的鈣離子作用,因為果膠的羧基與鈣離子及與營養組成物中存在的胜肽形成弱的膠結構,藉此導致黏度的增加。在一些實施例中,營養組成物包含澱粉對果膠的比例分別介於約12:1及20:1。在其他實施例中,澱粉對果膠的比例為約17:1。在一些實施例中,營養組成物可包含介於約0.05及約2.0% w/w之間的果膠。在特定實施例中,營養組成物可包含約0.5% w/w的果膠。
本文中所使用的果膠通常具有8,000道爾吞或更高的峰值分子量。本揭示之果膠的較佳峰值分子量介於8,000及約500,000之間,更佳為介於約10,000及約200,000之間,及最佳係介於約15,000及約100,000道爾吞之間。在一些實施例中,本揭示之果膠可為經水解的果膠。在特定實施例中,營養組成物包含具有比完整或未經修飾的果膠分子量更小的分子量的果膠。本揭示之經水解果膠可藉由本領域中已知的任何方法製備以降低分子量。所述方法的範例為化學水解、酵素水解及機械剪切。降低分子量的較佳方法為在高溫下藉由鹼或中性水解。在一些實施例中,營養組成物包含部分水解果膠。在特定實施例中,部分水解果膠具有比完整或未經修飾的果膠分子量更小的分子量但大於3,300道爾吞。
營養組成物可含有至少一酸性多糖。酸性多糖(諸如帶負電果膠)可誘導個體的胃腸道中致病原的抗黏附作用。的確,衍生自果膠的非人乳酸性多糖能夠與上
皮表面作用,且已知可抑制上皮表面上致病原的附著。
在一些實施例中,營養組成物包含至少一果膠衍生的酸性寡糖。果膠衍生的酸性寡糖(pAOS)源自酵素性果膠降解,且pAOS的尺寸取決於酵素使用及反應持續時間。在此實施例中,pAOS有益地影響個體的糞便黏度、排便次數、糞便pH及/或進食耐受性。本揭示之營養組成物包含介於每公升嬰兒配方約2g pAOS及每公升嬰兒配方約6g pAOS之間。在一實施例中,對應於人乳中酸性寡糖濃度,營養組成物包含約0.2g pAOS/dL(Fanaro et al.,“Acidic Oligosaccharides from Pectin Hydrolysate as New Component for Infant Formulae:Effect on Intestinal Flora,Stool Characteristics,and pH”,Journal of Pediatric Gastroenterology and Nutrition,41:186-190,August 2005)。
在一些實施例中,營養組成物包含高達約20% w/w的澱粉及果膠混合物。在一些實施例中,營養組成物包含高達約19%澱粉及高達約1%果膠。在其他實施例中,營養組成物包含高達約15%澱粉及高達約5%果膠。在其他實施例中,營養組成物包含高達約18%澱粉及高達約2%果膠。在一些實施例中營養組成物包含介於約0.05% w/w及約20% w/w之間的澱粉及果膠混合物。其他實施例包括介於約0.05%及約19% w/w澱粉與介於約0.05%及約1% w/w果膠。此外,營養組成物包含介於約0.05%及約15% w/w澱粉與介於約0.05%及約5% w/w果
膠。
用於本揭示之營養組成物的適當脂肪或脂質可為本領域中任何已知或慣用的,包括但不限於動物來源,如乳脂、奶油、黃油、黃油脂、蛋黃脂質;水產來源,如魚油、水產油、單細胞油;蔬菜及植物油,如玉米油、芥花籽油、葵花油、大豆油、軟質棕櫚油、椰子油、高油酸葵花油、月見草油、菜籽油、橄欖油、亞麻仁(亞麻籽)油、棉子油、高油酸紅花油、棕櫚硬脂、棕櫚仁油、小麥胚芽油;中鏈三酸甘油酯油、結構化脂質(如由Advanced Lipids製造之Infat®及由IOI Loders Croklaan供應之Betapol®。兩者皆為在sn-2位置富集棕櫚酸的三酸甘油酯)及脂肪酸的乳劑和酯類;及其任何組合。
在一實施例中,脂質或脂肪的量不大於約7g/100Kcal;在一些實施例中,脂質或脂肪以約2至約7g/100Kcal的濃度存在。
已發現肌醇的營養補充品在對於提升寡樹突細胞存活及增生表現出可行且有效的方法且呈現劑量依賴性,導致寡樹突細胞前趨細胞的數量一致上升。具有肌醇的營養補充品對強化髓鞘發育有益,藉此其轉為對腦部發育有基本益處。由於功能性髓鞘化的重要性,肌醇的營養補充品藉由強化腦部發育及健康而對小兒個體有益。此外,肌醇的甜味更提供幼兒消費者適口性的優點。
因此,在特定實施例中,肌醇以至少約4mg/100Kcal的濃度存在於本揭示之營養組成物中;在其
他實施例中,肌醇需以不大於約70mg/100Kcal的濃度存在。在其他實施例中,營養組成物包含約5mg/100Kcal至約65mg/100Kcal的濃度的之肌醇。在進一步實施例中,肌醇以約7mg/100Kcal至約50mg/100Kcal的濃度存在於營養組成物中。此外,肌醇可以外源性肌醇或固有性肌醇呈現。在實施例中,肌醇主要部分(即,至少40%)為外源性肌醇。在特定實施例中,外源性對固有性肌醇的比例為至少50:50;在其他實施例中,外源性對固有性肌醇的比例為至少60:40。
在一實施例中,營養組成物可含有一或多種益生菌。本領域已知之任何益生菌可適用於本實施例。在特定實施例中,益生菌可選自乳桿菌屬(Lactobacillus species)、鼠李糖乳桿菌GG(Lactobacillus rhamnosus GG,LGG)(ATCC編號53103)、雙歧桿菌屬(Bifidobacterium species)、長雙歧桿菌BB536(Bifidobacterium longum BB536)(BL999,ATCC:BAA-999)、長雙歧桿菌AH1206(NCIMB:41382)、短雙歧桿菌AH1205(Bifidobacterium breve AH1205)(NCIMB:41387)、嬰兒雙歧桿菌35624(Bifidobacterium infantis 35624)(NCIMB:41003)及動物雙歧桿菌乳雙歧亞種(Bifidobacterium animalis subsp.lactis BB-12)(DSM No.10140)或其任何組合。
若包括於組成物中,益生菌的量可變化自每100Kcal約1 x 104至約1.5 x 1012cfu之益生菌。在一些
實施例中,益生菌的量可為每100Kcal約1 x 106至約1 x 109cfu之益生菌。在某些其他實施例中,每100Kcal益生菌的量可變化自每100Kcal約1 x 107至約1 x 108cfu之益生菌。
在一實施例中,益生菌可為活性或無活性的。如本文中所使用的「活性」一詞意指活的微生物。用語「無活性」或「無活性益生菌」意指非活的益生菌微生物、其細胞組分及/或其代謝產物。此種無活性益生菌可經熱滅活(heat-killed)或其他方法而失活,但其保有有利地影響宿主健康的能力。不論此來源為現今已知的或往後發展出的,本揭示可使用的益生菌為自然存在的、合成的或藉由有機體的遺傳調控而發展的。
在一些實施例中,營養組成物可包括包含益生菌細胞等同物的來源,其意指無活性、無增殖的益生菌的濃度相當於等量的活性細胞。用語「無增殖」應理解為源自相同量的增殖細菌(cfu/g)(包括失活益生菌、DNA片段、細胞壁或細胞質化合物)的無增殖的微生物量。換句話說,假若所有微生物為活的(不論是否其為死亡的、無增殖的、失活的、破碎的等等),以cfu表示非活的、無增殖生物體的量。在營養組成物中所包括的無活性益生菌中,益生菌細胞等同物的量可變化自每100Kcal約1 x 104至約1.5 x 1010之益生菌細胞等同物。在一些實施例中益生菌細胞等同物的量為每100Kcal營養組成物約1 x 106至約1 x 109之益生菌細胞等同物。在某些其他實施例
中益生菌細胞等同物的量可變化自每100Kcal營養組成物約1 x 107至約1 x 108之益生菌細胞等同物。
在一些實施例中,併入營養組成物中的益生菌來源可包含活性的菌落形成單位及無活性的細胞等同物兩者。
在一些實施例中,營養組成物包括來自益生菌批量培養法的後指數生長期的培養上清液。不希望受到理論所束縛,咸信培養上清液的活性可歸因於被發現在益生菌批量培養的指數(或「對數」)期之後期釋放至培養基的組分混合物(包括蛋白膠物質,及可能包括(胞外)多糖物質)。如本文中所使用的「培養上清液」一詞包括在培養基中發現的組分混合物。細菌之批量培養階段的識別對本領域技術人員為周知的。該等為「延滯期」、「對數期(log)」(「對數(logarithmic)」或「指數(exponential)」、「停滯期」及「死亡期」(或對數衰亡期)。在活菌存在期間的所有階段中,細菌自基質代謝營養素,並分泌(送出、釋放)物質至培養基中。在生長階段的特定時間點的分泌物質組成物通常是不可預測的。
在一實施例中培養上清液可得自包含下列步驟之程序:(a)使用批量法在適當的培養基中進行培養諸如LGG之益生菌;(b)在培養步驟的後指數生長期收集培養上清液,該階段係參考批量培養法的延滯期及停滯期之間的後半段時間所定義;(c)自上清液任意地移除低分子量成分以保持分子量成分高於5-6千道爾吞
(kDa);(d)自培養上清液移除液體成分以獲得組成物。
培養上清液可包含自後指數期收集的分泌物質。後指數期發生於中指數期(其為指數期期間一半的時間,因此參考後指數期作為延滯期及停滯期之間的後半段時間)之後的時間。具體來說,本文中所使用之「後指數期」一詞參考LGG批量培養法的延滯期及停滯期之間的最後四分之一部分的時間。在一些實施例中,在指數期期間75%至85%的時間點收集培養上清液,且可在指數期時間經過約5/6時收集。
本揭示之營養組成物亦可包含β-葡聚糖來源。葡聚糖為多糖,特別是葡萄糖的聚合物,其為自然存在且可在細菌、酵母菌、真菌和植物的細胞壁中發現。β-葡聚糖本身為葡萄糖聚合物的不同子集,其為經由β型糖苷鍵將葡萄糖單體連結在一起的鏈所組成以形成複合碳水化合物。
β-1,3-葡聚糖為純化自例如酵母菌、菇類、細菌、海藻或穀物的碳水化合物聚合物(Stone BA,Clarke AE.Chemistry and Biology of(1-3)-Beta-Glucans.London:Portland Press Ltd;1993)。β-1,3-葡聚糖的化學結構取決於β-1,3-葡聚糖的來源。此外,各種理化參數(諸如溶解度、一級結構、分子量與分支)在β-1,3-葡聚糖的生物活性中扮演重要角色(Yadomae T.,Structure and biological activities of fungal beta-1,3-glucans.Yakugaku Zasshi.
2000;120:413-431)。
β-1,3-葡聚糖為自然存在的多糖,在多種植物、酵母菌、真菌及細菌的細胞壁中發現其伴隨或不伴隨著β-1,6-葡聚糖。β-1,3;1,6-葡聚糖為含有以(1,3)連接的葡萄糖單元,其具有附接於(1,6)位置的側鏈。β-1,3;1,6葡聚糖為異質基團之葡萄糖聚合物,其享有結構性的共同點,包括由β-1,3鍵連接的直鏈葡萄糖單元骨架,與自骨架延伸出β-1,6-連接的葡萄糖支鏈。然而此為現今所述之類別的β-葡聚糖的基本結構,可能出現某些變異型。例如,某些酵母β-葡聚糖具有延伸自β(1,6)支鏈的β(1,3)支鏈之額外區域,其進一步增加其各別結構之複雜性。
得自麵包酵母菌(啤酒酵母(Saccharomyces cerevisiae))的β-葡聚糖為由連接於位置1及3的D-葡萄糖分子之鏈組成,其在位置1及6附接有葡萄糖側鏈。得自酵母菌的β-葡聚糖為不可溶性的、纖維樣的複合糖,其具有以β-1,3骨架的葡萄糖單元的直鏈基本結構穿插一般為6至8個葡萄糖單元長的β-1,6側鏈。更具體地,得自麵包酵母菌的β-葡聚糖為聚-(1,6)-β-D-吡喃葡萄糖苷-(1,3)-β-D-吡喃葡萄糖。
此外,β-葡聚糖具有良好耐受性且對小兒個體不產生或導致過多氣體、腹脹、腹脹或腹瀉。對小兒個體營養組成物之β-葡聚糖的添加,諸如嬰兒配方奶粉、成長奶粉或其他孩童營養品將藉由增加對侵入致病原的抵抗
力而改善個體免疫,且因此維持或改善整體健康。
本揭示之營養組成物包含β-葡聚糖。在一些實施例中,β-葡聚糖為β-1,3;1,6-葡聚糖。在一些實施例中,β-1,3;1,6-葡聚糖為衍生自麵包酵母。營養組成物可包含全葡聚糖顆粒β-葡聚糖、微粒β-葡聚糖、PGG-葡聚糖(聚-1,6-β-D-吡喃葡萄糖苷-1,3-β-D-吡喃葡萄糖)或其任何組合。
在一些實施例中,組成物中存在的β-葡聚糖的量每100g組成物介於約0.010及約0.080g之間。在其他實施例中,營養組成物每份包含介於約4及約35mg之間的β-葡聚糖。在另一實施例中,營養組成物每8 fl.oz.(236.6mL)包含介於約5及約30mg之間的β-葡聚糖。在其他實施例中,營養組成物包含的β-葡聚糖的量足以提供每天介於約15mg及約90mg之間的β-葡聚糖。營養組成物可以多劑量遞送以達到全天遞送至個體的β-葡聚糖的目標量。
在一些實施例中,營養組成物中β-葡聚糖的量每100Kcal為介於約2.5mg及約17mg之間。在另一實施例中β-葡聚糖的量每100Kcal為介於約4mg及約17mg之間。
一或多種額外維生素及/或礦物質亦可以足以提供個體每日營養需求的量添加至營養組成物。本領域通常技術之人員應理解維生素及礦物質需求會改變,例如基於孩童的年齡。舉例來說,嬰兒的維生素及礦物質需求不
同於一至十三歲之間的孩童。因此,本實施例並非意在限制針對特定年齡族群的營養組成物,而是提供可接受的維生素及礦物質組分的範圍。
營養組成物可選地包括一或多種下列維生素或其衍生物:維生素B1(硫胺素(thiamin)、焦磷酸硫胺素、TPP、三磷酸硫胺素、TTP、鹽酸硫胺素、單硝酸硫胺素)、維生素B2(核黃素(riboflavin)、黃素單核苷酸、FMN、黃素腺嘌呤二核苷酸、FAD、乳黃素、卵黃素)、維生素B3(菸鹼酸、尼古丁酸、菸鹼醯胺、尼古丁醯胺、尼古丁醯胺腺嘌呤二核苷酸、NAD、尼古丁酸單核苷酸、NicMN、吡啶-3-羧酸)、維生素B3-前驅物色胺酸、維生素B6(吡哆醇、吡哆醛、吡哆胺、鹽酸吡哆醇)、泛酸(泛酸鹽、泛醇)、葉酸鹽(葉酸、葉酸素、喋醯麩胺酸)、生物素、維生素C(抗壞血酸)、維生素A(視黃醇、乙酸視黃酯、軟脂酸視黃酯、具有其他長鏈脂肪酸的視黃酯、視黃醛、視黃酸、視黃醇酯化物)、維生素D(沉鈣固醇、膽沉鈣醇、維生素D3、1,25,-二羥基維生素D)、維生素E(α-生育酚,α-生育酚乙酸酯、α-生育酚琥珀酸酯、α-生育酚菸酸酯、α-生育酚),維生素K(維生素K1、葉醌、萘醌、維生素K2、甲基萘醌-7、維生素K3、甲基萘醌-4、甲萘醌、甲基萘醌-8、甲基萘醌-8H、甲基萘醌-9、甲基萘醌-9H、甲基萘醌-10、甲基萘醌-11、甲基萘醌-12、甲基萘醌-13)、膽鹼、肌醇、β-胡蘿蔔素及其任何組合。
此外,營養組成物可選地包括,但不限於下列礦物質或其衍生物之一或多者:硼、鈣、乙酸鈣、葡萄糖酸鈣、氯化鈣、乳酸鈣、磷酸鈣、硫酸鈣、氯化物、鉻、氯化鉻、吡啶酸鉻、銅、硫酸銅、葡萄糖酸銅、硫酸銅(cupric sulfate)、氯、鐵、羰基鐵、三價鐵、反丁烯二酸亞鐵、正磷酸鐵、研磨鐵(iron trituration)、多糖鐵、碘化物、碘、鎂、碳酸鎂、氫氧化鎂、氧化鎂、硬脂酸鎂、硫酸鎂、錳、鉬、磷、鉀、磷酸鉀、碘化鉀、氯化鉀、乙酸鉀、硒、硫、鈉、多庫酯鈉(docusate sodium)、氯化鈉、硒酸鈉、鉬酸鈉、鋅、氧化鋅、硫酸鋅及其混合物。礦物質化合物的非限制性例示衍生物包括任何礦物質化合物之鹽、鹼鹽、酯及螯合物。
礦物質可以鹽的形式加入營養組成物中,諸如磷酸鈣、甘油磷酸鈣、檸檬酸鈉、氯化鉀、磷酸鉀、磷酸鎂、硫酸亞鐵、硫酸鋅、硫酸銅、硫酸錳及亞硒酸鈉。可添加本領域中已知之額外維生素及礦物質。
在一實施例中,針對特定國家營養組成物,每份之維生素A、C及E、鋅、鐵、碘、硒及膽鹼可含介於約10及約50%之間之最大膳食建議量,或針對一組國家介於約10及約50%之間之平均膳食建議量。在另一實施例中,針對任何特定國家的孩童營養組成物,每份之維生素B群可提供約10至30%之最大膳食建議量,或針對一組國家約10至30%之平均膳食建議量。在又另一實施例中,孩童營養品中的維生素D、鈣、鎂、磷及鉀的濃度
可與乳中發現的平均濃度對應。在其他實施例中針對任何特定國家,孩童營養組成物中的其他營養每份以約20%之最大膳食建議量存在,或針對一組國家約20%之平均膳食建議量。
本揭示之營養組成物可選地包括下列調味劑之一或多者,包括但不限於調味提取物、精油、可可或巧克力調味料、花生醬調味料、餅乾碎屑、香草或任何市售調味料。可用的調味料之範例包括,但不限於純八角萃取物、仿香蕉萃取物、仿櫻桃萃取物、巧克力萃取物、純檸檬萃取物、純橙萃取物、純薄荷萃取物、蜂蜜、仿鳳梨萃取物、仿蘭姆酒萃取物、仿草莓萃取物或香草萃取物;或精油,諸如香脂油(balm oil)、月桂油、佛手柑油、雪松木油、櫻桃油、桂皮油、丁香油或薄荷油;花生醬、巧克力調味料、香草餅乾碎屑、白脫糖、太妃糖及其混合物。取決於所使用的調味劑,調味劑的量可以變化很大。可選擇如本領域中已知的調味劑的種類及量。
本揭示之營養組成物可選地包括一或多種乳化劑,其可被添加以用於最終產品的安定性。適當的安定劑的範例包括,但不限於卵磷脂(例如來自蛋或大豆)、酪蛋白酸鈉、α乳白蛋白及/或單及雙甘油酯、果膠、經辛烯基琥珀酸(OSA)修飾之澱粉、經OSA修飾之麥芽糊精、經OSA修飾之果膠與該等之衍生物及其混合物。其他乳化劑對熟知此技術之人員為顯而易見的,且適合的乳化劑的選擇將(部份)取決於配方及最終產品。
本揭示之營養組成物可選地包括一或多種防腐劑,其亦可添加以延長產品保存期限。適合的防腐劑包括,但不限於山梨酸鉀、山梨酸鈉、苯甲酸鉀、苯甲酸鈉、乙二酸四乙酸二鈉鈣(calcium disodium EDTA)及其混合物。
本揭示之營養組成物可選地包括一或多種安定劑。在實踐本揭示之營養組成物中使用的適合的安定劑包括,但不限於阿拉伯膠、哥地膠、刺梧桐膠、黃蓍樹膠、洋菜膠、叉紅藻膠、瓜爾膠、結冷膠、刺槐豆膠、果膠、低甲氧基果膠、明膠、微晶纖維素、CMC(羧甲基纖維素鈉)、甲基纖維素羥丙基甲基纖維素、羥丙基纖維素、DATEM(單及雙脂肪酸甘油二乙醯酒石酸酯)、右旋糖酐、卡拉膠及其混合物。
可以本領域已知之任何形式提供所揭示之營養組成物,諸如粉末、膠、懸浮液、糊、固體、液體、液體濃縮物、還原奶粉替代品或即食產品。在特定實施例中,營養組成物可包含營養補充品、孩童營養品、嬰兒配方奶粉、人乳強化劑、成長奶粉或設計給嬰兒或小兒個體的任何其他營養組成物。本揭示之營養組成物包括,例如可口服攝取的健康增強物質,包括,例如食品、飲品、片劑、膠囊及粉末。此外,本揭示之營養組成物可被標準化為特定卡路里含量,其可以即食產品提供,或其可以濃縮形式提供。在一些實施例中,營養組成物為粒徑範圍在5μm至1500μm的粉末形式,更佳地範圍在10μm至
400μm。
若營養組成物為即食產品的形式,營養組成物的滲透壓介於約100及約1100mOsm/kg water之間,更典型地約200至約700mOsm/kg water。
所揭示之營養組成物可提供最低限度、部分或全部的營養支援。組成物可為營養補充品或代餐。組成物可為(但非必要)完整營養。在一實施例中,揭示之營養組成物為完整營養且含有適合類型及適量之脂質、碳水化合物、蛋白質、維生素及礦物質。脂質或脂肪的量典型地可變化自約1至約7g/100Kcal。蛋白質的量典型地可變化自約1至約7g/100Kcal。碳水化合物的量典型地可變化自6至約22g/100Kcal。
本揭示之營養組成物可進一步包括至少一種額外植物營養素。在人乳中被識別出的植物營養素(或其衍生物、共軛型或前驅物)優選的為包括在營養組成物中。一般來說,類胡蘿蔔素及多酚的膳食來源藉由哺乳的母親吸收並保留在乳汁中,使其提供給哺乳中的嬰兒。針對嬰兒或孩童配方奶粉的該些植物營養素添加物使此配方奶粉反映人乳的組成物及功能性並提升整體健康及安康。
舉例來說,在一些實施例中,本揭示之營養組成物包含(一份8 fl.oz.(236.6mL))介於約80及約300mg之間的花青素、介於約100及約600mg之間的原花青素、介於約50及約500mg之間的黃烷-3-醇或其任何組合或混合物。在其他實施例中,營養組成物包含蘋果
萃取物、葡萄籽萃取物或其組合或混合物。此外,營養組成物的至少一種植物營養素可衍生自任何單一或摻合水果、葡萄籽及/或蘋果或茶葉萃取物。
針對此揭示之目的,額外的植物營養素可以天然、純化、囊封及/或化學或酵素修飾的形式被添加,以提供所欲的口感及安定性質。在囊封的例子中,所欲的是經囊封的植物營養素抵抗被水溶解,但在到達小腸時釋放。此可藉由腸溶包衣(enteric coating)的應用來達成,諸如交聯的海藻酸鹽及其他。
適用於營養組成物的額外植物營養素的範例包話,但不限於花青素、原花青素、黃烷-3-醇類(即,兒茶素、表兒茶素等)、黃烷酮、類黃酮、異黃酮、類二苯乙烯(stilbenoid)(即,白藜蘆醇等)原花青素、花青素、白藜蘆醇、槲皮素、薑黃素及/或其任何組合,以及以純化或天然形式的植物營養素的任何可能組合。營養組成物的特定組分,尤其是以植物為基的組分可提供植物營養素的來源。
少量的植物營養素可固有地存在於已知成分(諸如天然油)中,其常用於製作針對小兒個體的營養組成物。這些固有植物營養素可以(但非必需)視為本揭示中所述之植物營養素組分的一部分。在一些實施例中,此處所述之植物營養素濃度及比例為基於添加的及固有的植物營養素來源而計算。在其他實施例中,此處所述之植物營養素濃度及比例為僅基於添加的植物營養素來源而計
算。
在一些實施例中,營養組成物包含花青素,諸如,例如橙苷色素(aurantinidin)、矢車菊素(cyanidin)、飛燕草素(delphinidin)、歐天芥菜色素(europinidin)、木樨草定(luteolinidin)、天竺葵苷素(pelargonidin)、錦葵花素(malvidin)、芍藥素(peonidin)、牽牛花素(petunidin)及薔薇素(rosinidin)的葡萄糖苷。適用於營養組成物的該等及其他花青素可在各種植物來源中發現。花青素可衍生自單一植物來源或植物來源的組合。適用於本發明組成物之富含花青素的植物的非限制性範例包括:漿果(巴西莓、葡萄、山桑、藍莓、越橘、黑加侖、山楸梅、黑莓、覆盆子、櫻桃、紅加侖、蔓越莓、紅莓苔子、雲莓、歐洲越橘、花楸果)、紫玉米、紫薯、紫胡蘿蔔、紅心地瓜、紫甘藍、茄子。
在一些實施例中,本揭示之營養組成物包含原花青素,其包括但不限於黃烷-3-醇及聚合度在2至11範圍內的黃烷-3-醇的聚合物(例如,兒茶素、表兒茶素)。此化合物可衍生自單一植物來源或植物來源的組合。適用於本揭示的營養組成物之富含原花青素的植物來源的非限制性實例包括:葡萄、葡萄皮、葡萄籽、綠茶、紅茶、蘋果、松樹皮、肉桂、可可、山桑、蔓越莓、黑加侖、山楸梅。
適用於本揭示之營養組成物的黃烷-3-醇的非
限制性範例包括兒茶素、表兒茶素、沒食子兒茶素、表沒食子兒茶素、表兒茶素沒食子酸酯、表兒茶素-3-沒食子酸酯、表沒食子兒茶素及沒食子酸酯。富含適合的黃烷-3-醇的植物包括,但不限於茶葉、紅葡萄、可可、綠茶、杏仁及蘋果。
特定多酚化合物(尤其是黃烷-3-醇)可藉由增加腦部血流量以改善人類個體的學習及記憶,腦部血流量與增加及維持腦部能量/養分遞送以及新神經元的形成有關。多酚也可提供神經保護作用且可增加腦部突觸新生及抗氧化能力兩者,藉此提供幼兒最佳的腦部發育。
用於營養組成物之較佳的黃烷-3-醇來源包括至少一蘋果萃取物、至少一葡萄籽萃取物或其混合物。對於蘋果萃取物,黃烷-3-醇被降解為存在有範圍4%至20%的單體及範圍80%至96%的聚合物。對於葡萄籽萃取物,黃烷-3-醇被降解為整體黃烷-3-醇及整體多酚內容物的單體(約46%)及聚合物(約54%)。聚合黃烷-3-醇的聚合度較佳介於2及11範圍之間。此外,蘋果及葡萄籽萃取物可含有兒茶素、表兒茶素、表沒食子兒茶素、表兒茶素沒食子酸酯、表沒食子兒茶素沒食子酸酯、聚合原青花素、類二苯乙烯(即,白藜蘆醇)、黃酮醇(即,槲皮素、楊梅素)或其任何混合物。富含黃烷-3-醇的植物包括,但不限於蘋果、葡萄籽、葡萄、葡萄皮、茶葉(綠茶或紅茶)、松樹皮、肉桂、可可、山桑、蔓越莓、黑加侖、山楸莓。
每日可施用的黃烷-3-醇的量(包括單體黃烷-3-醇、聚合黃烷-3-醇或其組合)範圍介於約0.01mg及約450mg之間。在一些例子中,每日施用給嬰兒或孩童的黃烷-3-醇的量範圍約0.01mg至約170mg、每日約50至約450mg或每日約100mg至約300mg。
在所揭示之一實施例中,存在於營養組成物中的黃烷-3-醇的量範圍自約0.4至約3.8mg/g營養組成物(約9至約90mg/100Kcal)。在另一實施例中,黃烷-3-醇存在的量範圍自約0.8至約2.5mg/g營養組成物(約20至約60mg/100Kcal)。
在一些實施例中,本揭示之營養組成物包含黃烷酮。適合的黃烷酮的非限制性範例包括紫鉚素(butin)、聖草素(eriodictyol)、橘皮苷素(hesperetin)、橘皮苷(hesperidin)、高聖草素(homeriodictyol)、異櫻花素(isosakuranetin)、柚皮素(naringenin)、柚皮苷(naringin)、松屬素(pinocembrin)、枸橘苷(poncirin)、櫻花素(sakuranetin)、櫻花苷(sakuranin)、史特賓(steurbin)。富含黃烷酮的植物來源包括,但不限於橙、柑橘、葡萄柚、檸檬、酸橙。營養組成物可配製成每天以介於約0.01及約150mg之間的黃烷酮範圍來遞送。
此外,營養組成物亦包含黃酮醇。可使用來自植物或海藻萃取物的黃酮醇。黃酮醇(諸如異鼠李素、楊梅素、槲皮素)可被包括於營養組成物中以足以每日遞送介於約0.01及150mg之間的黃酮醇至一個體。
營養組成物的植物營養素組分亦可包括在人乳中被識別出的植物營養素,包括但不限於柚皮素、橘皮苷素、花青素、槲皮素、山奈酚(kaempferol)、表兒茶素、表沒食子兒茶素、表兒茶素沒食子酸酯、表沒食子兒茶素沒食子酸酯或其任何組合。在特定實施例中,營養組成物包含介於約50及約2000nmol/L之間的表兒茶素、介於約40及約2000nmol/L之間的表兒茶素沒食子酸酯、介於約100及約4000nmol/L之間的表沒食子兒茶素沒食子酸酯、介於約50及約2000nmol/L之間的柚皮素、介於約5及約500nmol/L之間的山奈酚、介於約40及約4000nmol/L之間的槲皮素、介於約25及約2000nmol/L之間的花青素、介於約25及約500nmol/L之間的橘皮苷素或其混合物。此外,營養組成物可包含植物營養素或其親體化合物的代謝產物,或其可包含其他類別的膳食植物營養素,諸如硫化葡萄糖苷或蘿蔔硫素(sulforaphane)。
在特定實施例中,營養組成物包含類胡蘿蔔素,諸如葉黃素(lutein)、玉米黃素(zeaxanthin)、蝦紅素(astaxanthin)、番茄紅素(lycopene)、β-胡蘿蔔素、α-胡蘿蔔素、γ-胡蘿蔔素及/或β-隱黃素(beta-cryptoxanthin)。富含類胡蘿蔔素的植物來源包括,但不限於奇異果、葡萄、柑橘類、番茄、西瓜、木瓜及其他紅色水果或深綠色蔬菜,諸如甘藍菜、菠菜、蕪菁葉、不結球甘藍葉、半結球萵苣、花椰菜、綠皮西葫蘆、腕豆及球
芽甘藍、菠菜、胡蘿蔔。
人類無法合成類胡蘿蔔素,但在人類母乳中已識別出超過34種類胡蘿蔔素,包括特定胡蘿蔔素的異構物及代謝產物。除了在母乳中存在以外,膳食類胡蘿蔔素,諸如α-胡蘿蔔素、β-胡蘿蔔素、番茄紅素、葉黃素、玉米黃素、蝦紅素及隱黃素存在於哺乳期婦女及哺乳嬰兒的血清中。一般的類胡蘿蔔素經報導能改善細胞間通訊、提升免疫功能、支持健康的呼吸器官健康、保護皮膚免於UV光傷害且與降低某些種類的癌症風險及所造成的死亡率。此外,類胡蘿蔔素及/或多酚的膳食來源藉由人類個體吸收,累積並保留在母乳中,使其提供給哺乳中的嬰兒。因此,植物營養素對嬰兒配方奶粉或孩童產品的添加將使配方奶粉更接近人乳的組成物及功能性。
整體來說,由於類黃酮無法由人類所合成,故類黃酮可被包括於營養組成物中。此外,來自植物或海藻萃取物的類黃酮可以單體、二聚體及/或聚合物形式來使用。在一些實施例中,營養組成物包含類似於哺乳期前三個月期間的人乳中類黃酮單體形式濃度的類黃酮單體形式濃度。雖然已在人乳樣本中識別出類黃酮糖苷配基(單體),類黃酮及/或其代謝產物的共軛形式亦可用於營養組成物中。類黃酮可以下列形式被添加:自由型、醛糖酸化物、甲基醛糖酸化物、硫酸鹽及甲基硫酸鹽。
營養組成物亦可包含異類黃酮及/或異黃酮。範例包括,但不限於染料木素(染料木苷)、大豆黃素
(大豆苷)、黃豆黃素、鷹嘴豆素A(biochanin A)、芒柄花黃素(formononetin)、香豆雌酚(coumestrol)、德鳶尾素(irilone)、二羥四氫黃酮(orobol)、野靛黃素(pseudobaptigenin)、類安幾異黃酮A及B(anagyroidisoflavone A and B)、毛蕊異黃酮(calycosin)、黃豆黃酮(glycitein)、鳶尾黃素(irigenin)、5-O-甲基染料木素、紅車軸草素(pratensein)、櫻黃素(prunetin)、Ψ-鳶尾配質(psi-tectorigenin)、瑞士黃酮(retusin)、鳶尾配質、銀杏藻(iridin)、芒柄花苷(ononin)、葛根素(puerarin)、鳶尾苷(tectoridin)、德拉酮(derrubone)、羽扇豆異黃酮(luteone)、懷特酮(wighteone)、貓尾草異黃酮(alpinumisoflavone)、吡喃異黃酮(barbigerone)、二-O-甲基貓尾草異黃酮及4'-甲基貓尾草異黃酮。富含異類黃酮的植物包括,但不限於大豆、補骨脂屬(psoralea)、葛屬(kudzu)、羽扇豆(lupine)、蠶豆、鷹嘴豆、苜蓿、豆科植物及花生。營養組成物可配製成每天遞送介於約0.01至約150mg的異黃酮及/或類異黃酮。
在一實施例中,本揭示之營養組成物包含有效量之膽鹼。膽鹼為正常功能細胞所需的營養素。其為膜磷脂的前驅物,且其加速乙醯膽鹼(參與記憶儲存的神經傳遞物質)的合成及釋放。此外,雖不期望受此或任何其他理論所束縛,咸信膳食的膽鹼及二十二碳六烯酸
(DHA)協同地作用以促進卵磷脂的生物合成,且因此幫助促進人類個體的突觸新生。另外,膽鹼及DHA可表現促進樹突棘形成的協同效應,其在已建立的突觸連接的維持很重要。在一些實施例中,本揭示之營養組成物包括有效量的膽鹼,其為每8 fl.oz.(236.6mL)約20mg膽鹼至每8 fl.oz.(236.6mL)100mg膽鹼。
此外,在一些實施例中,營養組成物為完整營養,含有個體的唯一營養來源適合類型及適量的脂質、碳水化合物、蛋白質、維生素及礦物質。實際上,營養組成物可選地包括任何數量之蛋白質、胜肽、胺基酸、脂肪酸、益生菌及/或其代謝副產物、益菌生、碳水化合物及任何其他營養或可提供個體許多營養及生理上的益處的其他化合物。此外,本揭示之營養組成物可包括調味劑、增味劑、甜味劑、色素、維生素、礦物質、治療成分、功能性食物成分、食物成分、加工成分或其組合。
本揭示進一步提供用於對個體提供營養支持的方法。該方法包括對個體施用本揭示之有效量之營養組成物。
營養組成物可直接地排入個體的腸道中。在一些實施例中,營養組成物係直接地排入腸道中。在一些實施例中,基於公認的科學原則透過醫學評估所發表,組成物可在醫師的建議下被配製為在腸道中消耗或施用,且旨在用於獨特的營養需求的疾病或病症(諸如腹腔疾病及/或食物過敏)的特殊膳食管理。
本揭示之營養組成物不限於本文中特別列出包含營養成分的組成物。針對滿足營養需求及/或為了最佳化個體的營養狀態的目的,任何營養成分可作為組成物的一部分被遞送。
在一些實施例中,營養組成物可遞送給出生至滿足足月妊娠的時間的嬰兒。在一些實施例中,營養組成物可遞送給直到至少約三個月大的矯正年齡的嬰兒。在另一實施例中,營養組成物可遞送給只要有需要校正營養缺乏的個體。在又另一實施例中,營養組成物可遞送給出生至至少約六個月大矯正年齡的嬰兒。在又另一實施例中,營養組成物可遞送給出生至至少約一年矯正年齡的嬰兒。
本揭示之營養組成物可標準化為特定卡路里含量,其可以即食產品提供,或其可以濃縮形式提供。
在一些實施例中,本揭示之營養組成物為成長奶粉。成長奶粉為針對超過1歲(通常1至3歲、4至6歲或1至6歲)孩童的強化乳為基的飲品。其並非醫療食品且不意欲作為代餐或解決特定營養缺乏的補給品。反之,成長奶粉為設計以意欲作為多樣化飲食的補充品以提供孩童得到連續的、每日的攝取所有必需維生素及礦物質、添加額外功能性膳食組分的巨量營養素(諸如旨在提升健康性質的非必需營養素)的額外保障。
根據本揭示營養組成物之特定組成物在市場間不同,取決於當地法規及人口感興趣的膳食攝取資訊。
在一些實施例中,根據所揭示之營養組成物由乳蛋白來源(諸如全脂乳或脫脂乳)、加上額外的糖及甜味劑以達到想要的口感特性、及額外的維生素與礦物質組成。脂肪組成物一般衍生自乳原料。可將整體蛋白質設定目標以符合人乳、牛乳或較低的值。整體碳水化合物通常設定目標以提供盡可能少量額外的糖(諸如蔗糖或果糖)以獲得可接受的口味。一般來說,添加維生素A、鈣及維生素D至符合原始牛乳營養素貢獻的濃度。除此之外,在一些實施例中,可添加維生素及礦物質,以提供每份約20%之膳食營養素參考攝入量(dietary reference intake,DRI)或20%之每日需求量(Daily Value,DV)。此外,營養價值在市場間可能不同,取決於預期人口經識別的營養需求,原料貢獻與地方法規。
在特定實施例中,營養組成物為低過敏性的。在其他實施例中,營養組成物為猶太律法食物及/或清真律法食物。在又進一步實施例中,營養組成物為非基因改造產品。在一實施例中,該營養配方為無蔗糖的。該營養組成物亦可為無乳糖的。在其他實施例中,營養組成物不含有任何中鏈三酸甘油脂油。在一些實施例中,組成物不存在鹿角菜膠。在其他實施例中,營養組成物不含有所有膠。
在一些實施例中,本揭示為涉及針對小兒個體(諸如嬰兒或孩童)的分段營養供應方案,其包括根據本揭示之複數個不同的營養組成物。本文中所述之營養組
成物可每日施用一次或在一整天期間數次施用。
提供範例以說明本揭示之營養組成物的某些實施例不應解釋為任何限制性的範例。在本文中所揭示之營養組成物或方法的說明書或實踐的認知下,本文中申請專利範圍的範圍內的其他實施例對本領域中之技術人員將是顯而易見的。其意圖是,說明書(連同範例)與由該範例之後的申請專利範圍指出的揭示之範圍及精神僅視為例示性。
根據本揭示之例示性配方如下:
根據本揭示之另一例示性配方如下:
根據本揭示之又另一例示性實施例如下:
根據本揭示之更另一例示性配方如下:
當施予給小兒個體本揭示之營養組成物時,就小腸健康、免疫、健康成長及腦部發育而言能提供廣泛益處,最佳地提供增效化合以改善認知嬰兒或孩童的認知發展。
在本說明書中引用的參考文獻,包括而不限於所有論文、出版物、專利、專利說明書、演講、教科書、報告、手稿、手冊、書藉、網路文章、期物文章、期刊等藉由引用全文而併入本說明書中。本文中參考文獻的討論目的僅在於總結其作者所作出的主張且不承認任何參考文獻構成現有技術。申請人保留質疑所引用參考文獻的準確性及相關性的權利。
雖然已使用具體術語、裝置及方法描述本揭示之實施例,此描述僅用於說明的目的。所使用的詞彙為描述而非限制性的詞彙。應理解本領域之普通技術人員可進行修改及變化,而不脫離下列申請專利範圍所闡述之本揭示的精神或範圍。此外,應理解各種實施例的態樣可整體的或部分的互換。因此,所附的申請專利範圍的精神及範圍不應被限定於在此包含的說明書版本中。
Claims (15)
- 一種用於增強小兒個體認知發展的方法,該方法包含對該個體施用包含下列之營養組成物:高達7g/100Kcal之脂肪或脂質;高達5g/100Kcal之蛋白質或蛋白質等同物來源;0.06g/100Kcal至1.5g/100Kcal之強化乳製品;5mg/100Kcal至90mg/100Kcal之長鏈多不飽合脂肪酸的來源;及0.015g/100Kcal至1.5g/100Kcal之益菌生。
- 如申請專利範圍第1項之方法,其中該強化乳製品係以0.3g/100Kcal至1.4g/100Kcal的濃度存在。
- 如申請專利範圍第2項之方法,其中該強化乳製品係以一濃度存在,使得該營養組成物包含6mg/100Kcal至300mg/100Kcal之磷脂、1mg/100Kcal至30mg/100Kcal之神經鞘磷脂、及0.25mg/100Kcal至6mg/100Kcal之神經節苷脂。
- 如申請專利範圍第3項之方法,其中該強化乳製品包含一強化乳清蛋白濃縮物。
- 如申請專利範圍第1項之方法,其中該營養組成物進一步包含5mg/100Kcal至300mg/100Kcal之濃度的乳鐵蛋白。
- 如申請專利範圍第5項的方法,其中該乳鐵蛋白係來自非人來源的乳鐵蛋白。
- 如申請專利範圍第5項之方法,其中該乳鐵蛋白 與人乳鐵蛋白具有至少48%同源性。
- 如申請專利範圍第1項之方法,其中該長鏈多不飽合脂肪酸的來源包括二十二碳六烯酸、二十碳四烯酸、及其組合之至少一者。
- 如申請專利範圍第8項之方法,其中該長鏈多不飽合脂肪酸的來源係以約5mg/100Kcal至約75mg/100Kcal存在。
- 如申請專利範圍第9項之方法,其中該長鏈多不飽合脂肪酸的來源包括二十二碳六烯酸及二十碳四烯酸,二十碳四烯酸對二十二碳六烯酸的比率為約1:3至約9:1。
- 如申請專利範圍第1項之方法,其中該益菌生組成物包含聚葡萄糖及半乳糖寡糖,其中聚葡萄糖及半乳糖寡糖為益菌生組成物的至少約20%。
- 如申請專利範圍第11項之方法,其中各聚葡萄糖係以約0.015g/100Kcal至約1.5g/100Kcal的濃度存在,且半乳糖寡糖係以約0.015g/100Kcal至約1.5g/100Kcal的濃度存在。
- 如申請專利範圍第1項之方法,其中該營養組成物進一步包含唾液酸、短鏈脂肪酸、維生素B12、或其組合。
- 如申請專利範圍第13項之方法,其中該短鏈脂肪酸係選自由下列組成的群組:丁酸、己酸、及其組合物。
- 如申請專利範圍第1項之方法,其中該營養組成物係嬰兒配方奶粉或成長奶粉。
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