TW201608996A - 含十八碳四烯酸之營養組成物及其用途 - Google Patents
含十八碳四烯酸之營養組成物及其用途 Download PDFInfo
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Classifications
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/19—Dairy proteins
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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Abstract
一種用於增進小兒個體腦部發育之組成物及方法,該方法包含投予小兒個體包括至少約0.08g/100kcal之十八碳四烯酸的營養組成物。
Description
本揭示內容大致上關於適合用於投予小兒個體之營養組成物。更特別地,本揭示內容關於含有十八碳四烯酸(stearidonic acid)之營養組成物,及關於藉由投予本揭示內容之營養組成物來支持和促進小兒個體之眼睛和認知發展及腦部功能之方法。於某些實施態樣中,該營養組成物亦包括γ-次亞麻油酸(gamma-linolenic acid)。於一些實施態樣中,該營養組成物包括富含十八碳四烯酸(SDA)和γ-次亞麻油酸(GLA)之植物油,以及包括聚右旋糖(polydextrose)和半乳寡醣(galacto-oligosaccharide)之益菌素(prebiotic)摻合物、乳鐵蛋白(lactoferrin)和另外的長鏈多不飽和脂肪酸來源,其中前述組分可展現加成及/或協同之有益效果。
十八碳四烯酸為從α-次亞麻油酸(ALA)代謝衍生之ω-3脂肪酸(一種長鏈多不飽和脂肪酸(LCPUFA)),其再轉化成二十碳五烯酸(eicosapentaenoic acid)(EPA)及二
十二碳六烯酸(docosahexaenoic acid)(DHA)。因此,SDA可被視為前-EPA及前-DHA脂肪酸。SDA天然存在於下列者中:魚油、一些可食用之藻類物種及數種植物(諸如麻、黑醋栗、田紫草(corn gromwell)和藍薊(echium))種子油,並可由螺旋藻(cyanobacterium Spirulina)製造。γ-次亞麻油酸為天然存在於植物油(月見草、黑醋栗、琉璃苣)和卵中之ω-6脂肪酸。
最近已發現在營養組成物中包含富含SDA和GLA之植物油,尤其是加上益菌素(諸如聚右旋糖(PDX)和半乳寡糖(GOS))、乳鐵蛋白及其他長鏈多不飽和脂肪酸(LCPUFA)時,可導致某些獨特的利益。因此,提供小兒個體此類營養組成物會是有利的。
簡言之,於一實施態樣中,本揭示內容係關於支持和促進小兒個體之眼睛發育、認知發展及腦部功能之方法,該方法包含投予小兒個體營養組成物,其包括十八碳四烯酸,隨意地具有益菌素(尤其是聚右旋糖(PDX)和半乳寡醣(GOS))、來自非人來源之乳鐵蛋白、及其他長鏈多不飽和脂肪酸(LCPUFA)。於一些實施態樣中,該營養組成物進一步包括γ-次亞麻油酸。於某些實施態樣中,該方法包含投予包括下列者之營養組成物:a.至多約7g/100kcal之脂肪或脂質來源,更佳為約3g/100kcal至約7g/100kcal之脂肪或脂質來源,其中該脂
肪或脂質來源包含至少約0.5g/100kcal、更佳為約1.5g/100kcal至約7g/100kcal之富含十八碳四烯酸和γ-次亞麻油酸的植物油;b.至多約7g/100kcal之蛋白質或蛋白質等效來源(protein equivalent source),更佳為約1g/100kcal至約7g/100kcal之蛋白質來源或蛋白質等效來源;及c.至少約5g/100kcal之碳水化合物,更佳為約5g至約25g/100kcal之碳水化合物。
於一些實施態樣中,該營養組成物進一步包括:d.至少約10mg/100kcal之乳鐵蛋白,更佳為約10mg/100kcal至約200mg/100kcal之乳鐵蛋白;e.約0.1g/100kcal至約1g/100kcal之包含PDX和GOS的益菌素組成物;及/或f.至少約5mg/100kcal之包含DHA之另外的LCPUFA(即,SDA或GLA以外的LCPUFA),更佳為約5mg/100kcal至約75mg/100kcal之包含DHA之另外的LCPUFA。
於其他實施態樣中,本揭示內容係關於藉由投予小兒個體包含十八碳四烯酸及益菌素、來自非人來源之乳鐵蛋白和另外的LCPUFA的營養組成物來支持小兒個體健康生長及發育的方法。
應理解的是,前文之一般描述及以下的詳細描述係皆給出本揭示內容之實施態樣且旨在提供用於理解
本案請求保護之內容之性質及特性的概述或架構。該描述係用於解釋申請專利之標的的原理和運作。熟習本技藝之人士在閱讀以下之揭示內容後將可輕易地明白本揭示內容之其他和進一步特徵及優點。
現在參照本揭示內容之實施態樣的詳細內容,下文中提出其一或多個實施例。所提供之各實施例係用於解釋本揭示內容之營養組成物,而非限制。事實上,熟習本技藝之人士將清楚明白本揭示內容之教示可在不偏離本揭示內容之範圍下做各種修改及變化。例如,所說明或描述之為一實施態樣之一部分的特徵可與另一實施態樣一起使用以產生另外的實施態樣。
因此,本揭示內容意圖涵蓋在所附之申請專利範圍及其等效者之範圍內的此等修改和變化。本揭示內容之其他目的、特徵及態樣係揭露於下列之詳細描述中或可從其中顯明。本技術領域之一般技術人士應理解本論述內容僅係描述示例性實施態樣,而不欲限制本揭示內容之更廣泛的態樣。
本揭示內容大致上關於營養組成物,尤其是適合投予小兒個體之以乳為底質的營養組成物。此外,本揭示內容關於藉由投予所揭示之營養組成物來支持和促進小兒個體之眼睛發育、認知發展及腦部功能的方法。
“營養組成物”意指滿足個體之至少一部分
營養需求的物質或調配物。在本揭示內容之全文中,術語“營養”、“營養配方”、“腸內營養”及“營養補充劑”係作為營養組成物之非限制性實例。再者,“營養組成物”可指液體、粉劑、凝膠、糊劑、固體、濃縮物、懸浮液或即時使用形式之腸內配方、口服配方、嬰兒配方、小兒個體配方、兒童配方、成長乳及/或成人配方。
術語“腸內”意指可經由胃腸道或消化道傳送或在胃腸道或消化道內傳送。“腸內投予”包括經口餵食、胃內餵食、經幽門投予或任何其他進入消化道之投予。“投予”較“腸內投予”更廣義且包括胃腸道外投予或任何其他將物質投入個體體內的投予途徑。
“小兒個體”係指不大於13歲的人。於一些實施態樣中,小兒個體係指介於出生和8歲之間的人個體。於其他實施態樣中,小兒個體係指介於1和6歲之間的人個體。於另外之實施態樣中,小兒個體係指介於6和12歲之間的人個體。術語“小兒個體”可指如下述之嬰兒(早產兒或足月兒)及/或兒童。
“嬰兒”意指年齡在出生到不超過一歲之範圍內的人個體且包括0至12個月矯正年齡之嬰兒。“矯正年齡(corrected age)”一詞意指嬰兒之實足年齡減去嬰兒早產的時間量。因此,矯正年齡為嬰兒若足月出生的年齡。術語嬰兒包括低出生體重兒、非常低出生體重兒、極低出生體重兒及早產兒。“早產兒”意指在妊娠第37週結束前出生的嬰兒。“晚期早產兒”意指在妊娠第34週和
第36週之間出生的嬰兒。“足月兒”意指在妊娠第37週結束後出生之嬰兒。“低出生體重兒”意指出生體重低於2500克(約5磅8盎司)之嬰兒。“非常低出生體重兒”意指出生體重低於1500克(約3磅4盎司)之嬰兒。“極低出生體重兒”意指出生體重低於1000克(約2磅3盎司)之嬰兒。
“兒童”意指年齡在12個月至13歲之範圍內的個體。於一些實施態樣中,兒童為年齡介於1歲和12歲之間的個體。於其他實施態樣中,術語“兒童們”或“兒童”係指介於1和約6歲之間、或介於約7和約12歲之間的個體。於其他實施態樣中,術語“兒童們”或“兒童”係指介於12個月和約13歲之間的任何年齡範圍。
“兒童營養產品”係指滿足兒童之至少一部分營養需求的組成物。成長乳為兒童營養產品之一實例。
術語“水解度”係指肽鍵被水解方法破壞之程度。
術語“部分水解的”意指其水解度大於0%但小於約50%。
術語“高度水解的(extensively hydrolyzed)”意指其水解度大於或等於約50%。
術語“不含蛋白質”意指當藉由標準蛋白質檢測法(諸如十二烷基(月桂基)硫酸鈉-聚丙烯醯胺(polyacrylamide)凝膠電泳法(SDS-PAGE)或粒徑排阻層析
法(size exclusion chromatography))測量時不含有可測得之蛋白質量。於一些實施態樣中,該營養組成物實質上不含蛋白質,其中“實質上不含”之定義如下。
“嬰兒配方”意指滿足嬰兒之至少一部分營養需求的組成物。在美國,嬰兒配方之內容係由21 C.F.R.章節100、106及107中所載之聯邦法規規定。這些法規界定大量營養素(macronutrient)、維生素、礦物質及其他成分之含量以努力模擬人類母乳之營養及其他性質。
術語“成長乳”係指欲作為多樣化膳食之一部分以支持年齡介於約1和約6歲之間的兒童正常生長和發育的廣大類別之營養組成物。
“以乳為底質”意指包含至少一種已從哺乳動物之乳腺提出或萃取之組分。於一些實施態樣中,以乳為底質之營養組成物包含源自馴養之有蹄類動物、反芻動物或其他哺乳動物或彼等之任何組合的乳汁組分。再者,於一些實施態樣中,以乳為底質意指包含牛酪蛋白、乳清、乳糖或彼等之任何組合。此外,“以乳為底質之營養組成物”可指包含本技術領域中已知之任何源自乳汁或以乳為底質之產品的任何組成物。
“營養完整的”意指可作為唯一之營養來源的組成物,該組成物可實質上供應所有每日需要量之維生素、礦物質及/或微量元素,加上蛋白質、碳水化合物和脂質。確切地,“營養完整的”係描述能提供適量之支持
個體正常生長和發育所需的碳水化合物、脂質、必需肪酸、蛋白質、必需胺基酸、半必需胺基酸、維生素、礦物質及能量的營養組成物。
因此,根據定義,對早產兒而言為“營養完整”之營養組成物將提供質與量上適量之早產兒生長所需的碳水化合物、脂質、必需脂肪酸、蛋白質、必需胺基酸、半必需胺基酸、維生素、礦物質及能量。
根據定義,對足月兒而言為“營養完整”之營養組成物將提供質與量上適量之足月兒生長所需的全部碳水化合物、脂質、必需脂肪酸、蛋白質、必需胺基酸、半必需胺基酸、維生素、礦物質及能量。
根據定義,對兒童而言為“營養完整”之營養組成物將提供質與量上適量之兒童生長所需的全部碳水化合物、脂質、必需脂肪酸、蛋白質、必需胺基酸、半必需胺基酸、維生素、礦物質及能量。
當應用於營養素時,術語“必需”係指身體無法合成足夠用於正常生長及維持健康之量,因此必需由膳食供應的任何營養素。當應用於營養素時,術語“半必需”意指當身體無法取得適量之前體化合物以發生自行合成時,必需由膳食提供之營養素。
“益生菌(probiotic)”意指能對宿主健康發揮有益影響之具有低或無致病性的微生物。
術語“失活之益生菌”意指其中所指之益生菌的代謝活性或繁殖能力已被降低或破壞。然而,“失活之
益生菌”在細胞層級、仍保留其細胞結構或其他與該細胞相關之結構(例如胞外多醣)及至少一部分其生物醣蛋白及DNA/RNA結構。如本文所使用之術語“失活”係與“非存活”同義。
“益菌素”意指能藉由選擇性地刺激消化道內一或有限數量之可促進宿主健康的細菌之生長及/或活性而有利地影響宿主之不易消化的食品成分。
“β-葡聚醣”意指所有β-葡聚醣,包括特定類型之β-葡聚醣,諸如β-1,3-葡聚醣或β-1,3;1,6-葡聚醣。再者,β-1,3;1,6-葡聚醣為β-1,3-葡聚醣之一種類型。因此,術語“β-1,3-葡聚醣”包括β-1,3;1,6-葡聚醣。
如本文所使用之“來自非人來源之乳鐵蛋白”意指由人類母乳以外之來源製造或從人類母乳以外之來源取得的乳鐵蛋白。例如,用於本揭示內容中之乳鐵蛋白包括藉由基改有機體製造之人乳鐵蛋白及非人乳鐵蛋白。如本文所使用之術語“有機體”係指任何連續存活系統,例如動物、植物、真菌或微生物。如本文所使用之術語“非人乳鐵蛋白”係指其所具有之胺基酸序列與人乳鐵蛋白所具有之胺基酸序列不同的乳鐵蛋白。
如本文所使用之“非人乳鐵蛋白”意指其所具有之胺基酸序列與人乳鐵蛋白所具有之胺基酸序列不同的乳鐵蛋白。
“病原體”意指引起疾病狀態或病理症候群之有
機體。病原體之實例可包括細菌、病毒、寄生蟲、真菌、微生物或彼等之組合。
“調整(modulate或modulating”)意指施加修改、控制及/或調節性影響。於一些實施態樣中,術語“調節”意指對特定組分之水平/量展現出增加或刺激效果。於其他實施態樣中,“調節”意指對特定組分之水平/量展現降低或抑制效果。
除非另外具體指明,本文所使用之所有百分比、份及比例係按總調配物重量計。
所有具體指定為“每天”投予之量可在24小時之期間內以單一劑量、以單份用量或以二或更多劑量或用量投予。
本揭示內容之營養組成物可實質上不含任何本文所描述之隨意的或可選擇之成分,惟其餘營養組成物仍含有所有本文所描述之所需的成分或特性。本文中,除非另外具體指明,術語“實質上不含”意指所選擇之組成物所含有之隨意的成分可能少於該成分之功能量(functional amount),通常少於0.1重量%,且亦包括0重量%之這類隨意的或可選擇之成分。
除非所提及者之上下文另外具體指明或明確暗示相反之意,本揭示內容中所有提及之單數特性或限制應包括對應之複數特性或限制,反之亦然。
除非所提組合之上下文另外具體指明或明確暗示相反之意,本文所使用之所有方法或製程步驟的所有
組合可以任何順序執行。
本揭示內容之方法和組成物(包括其組分)可包含下列、由下列組成、或主要由下列組成:本文所描述之實施態樣的必須要素和限制,以及本文所描述或營養組成物中有用之任何額外或隨意之成分、組分或限制。
本文所使用之術語“約”應解釋為係指被具體指定作為任何範圍之端點之兩數字。對範圍之任何引用應被視為係提供對該範圍內之任何子集的支持。
本揭示內容係關於包含十八碳四烯酸之以乳為底質的營養組成物,且於某些實施態樣中,包含γ-次亞麻油酸。於一些實施態樣中,該營養組成物進一步包括益菌素、乳鐵蛋白及另外的LCPUFA來源。關於該營養組成物之用途,及包含投予該等營養組成物之方法。本揭示內容之營養組成物支持人類小兒個體(諸如嬰兒(早產兒及/或足月兒)或兒童)之整體健康和發育。
在嬰兒中,腸道不成熟往往造成影響其營養狀態之胃腸道症狀,結果影響其整體健康。於一些實施態樣中,本揭示內容係關於支持腸道發育及經由腸-腦軸之腸道與腦部之聯繫的營養組成物。再者,本揭示內容之營養組成物可正面影響腦部相關的功能。因此,於一些實施態樣中,本揭示內容係關於調節腸-腦聯繫之方法。
攝取本揭示內容之營養組成物可正面影響小兒個體中涉及認知、記憶、學習、情緒調節和動作協調之腦部區域,以及促進眼睛發育。此外,使用益菌素,尤其
是PDX和GOS會改變中樞神經系統內之生物胺(biogenic amine)和神經傳導物質(neurotransmitter)的製造,且該此變化可以解釋餵食PDX/GOS對社交技巧、焦慮和記憶功能的有益效果。再者,含有乳鐵蛋白可改善個體對壓力狀況的適應性,並分別改善學習能力。總之,本揭示內容之營養組成物可經由修飾腸道微生物相(microflora)、優化眼睛之發育及腦部組成、並改善多種與腦部相關之行為和功能而在嬰兒和兒童期發揮重要作用。
如所指者,本揭示內容之營養組成物包括十八碳四烯酸。於某些實施態樣中,營養組成物中之SDA的存在量為至少約0.08g/100kcal。於其他實施態樣中,SDA之存在量為約0.25g/100kcal至約3g/100kcal。再於其他實施態樣中,營養組成物中之SDA的存在量為約0.5g/100kcal至約1.5g/100kcal。
當本揭示內容之營養組成物亦包括γ-次亞麻油酸時,營養組成物中之GLA的存在量為至少約0.03g/100kcal。於其他實施態樣中,GLA之存在量為約0.08g/100kcal至約1g/100kcal。再於其他實施態樣中,營養組成物中之GLA的存在量為約0.2g/100kcal至約0.5g/100kcal。
於某些實施態樣中,SDA和GLA(當存在時)係藉由使用富含SDA之植物油,尤其是富含SDA之蔬菜油而被納入該營養組成物中。一般而言,使植物油富含SDA可藉由各種方法中之任一者來完成,包括藉由遺傳工
程修飾該油之植物來源的基因改造。例如,由Monsanto公司開發之富含SDA的大豆油係藉由引入二個編碼蛋白質,茱莉亞報春(Primula juliae)△6去飽和酶及紅麵包黴(Neurospora crassa)△15去飽和酶,之去飽和酶基因來製造。大豆缺乏△6去飽和酶,而在大豆中製造SDA的最低要求為引入編碼△6去飽和酶之基因。再者,△6去飽和酶亦可導致GLA之製造。加入△15去飽和酶(時間表現(temporal expression)與△6去飽和酶類似)會增加ALA至SDA之通量(flux)。△15去飽和酶亦可降低製造GLA之受質池(substrate pool)。
本揭示內容之營養組成物可透過以富含SDA之植物油取代組成物中之脂質或脂肪組分來補充SDA和GLA。
用於本揭示內容之營養組成物的合適脂肪或脂質來源可為任何本技術領域中所已知或使用者,包括,但不限於動物來源,例如乳脂肪、奶油、奶油脂肪、蛋黃脂質;海洋來源,諸如魚油、海洋生物油、單細胞油;植物和植物油,諸如玉米油、芥花油、葵花油、大豆油、軟棕櫚油(palm olein oil)、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、棉籽油、高油酸紅花油、棕櫚油硬脂、棕櫚仁油、小麥胚芽油;中鏈三酸甘油脂油類和乳劑及脂肪酸之酯類;以及彼等之任何組合。於一特定實施態樣中,脂肪或脂質來源包含以相對等份混合之棕櫚油、葵花油和紅花油的混合物。
營養組成物中之脂肪或脂質來源的存在量至多為約7g/100kcal;於實施態樣中,脂肪或脂質來源之存在量為約3g/100kcal至約7g/100kcal。當補充富含SDA之植物油時,脂肪或脂質來源包含至少約0.3g/100kcal、更佳地約0.5g/100kcal至約7g/100kcal之富含十八碳四烯酸的植物油,諸如富含SDA之大豆油。
本揭示內容之營養組成物亦可包含至少一種非乳鐵蛋白蛋白質或蛋白質等效來源(protein equivalent source),此係指乳鐵蛋白以外之蛋白質或蛋白質等效來源。蛋白質或蛋白質等效來源可為本技術領域中所使用之任一者,例如脫脂乳、乳清蛋白、酪蛋白、大豆蛋白、水解蛋白、胺基酸,等。用於實行本揭示內容之牛乳蛋白來源包括,但不限於乳蛋白粉、乳蛋白濃縮物、乳蛋白分離物、脫脂乳固體、脫脂乳、脫脂乾乳、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、酸酪蛋白、酪蛋白酸鹽(caseinate)(例如酪蛋白酸鈉、酪蛋白酸鈣鈉、酪蛋白酸鈣)及彼等之任何組合。
於一些實施態樣中,營養組成物之蛋白質係以完整蛋白質之形式提供。於其他實施態樣中,蛋白質係以完整蛋白質和水解蛋白兩者之組合提供。於某些實施態樣中,蛋白質可為部分水解或高度水解的。再於其他實施態樣中,蛋白質來源包含胺基酸。再於另一實施態樣中,蛋白質來源可補充含有麩醯胺酸之肽類。於另一實施態樣中,蛋白質組分包含高度水解之蛋白質。再於另一實施態
樣中,營養組成物之蛋白質組分實質上由高度水解之蛋白質所組成,以將食物過敏的發生減至最少。再於另一實施態樣中,蛋白質來源可補充含有麩醯胺酸之肽類。
一些人表現出對完整蛋白質,即,全蛋白(諸如那些在以完整牛乳蛋白或以完整大豆蛋白分離物為底質之配方中者)過敏或敏感。這些具有蛋白過敏或敏感之人中有許多人能夠耐受水解蛋白。水解物配方(亦稱為半要素(semi-element)配方)含有已水解或分解成短肽片段和胺基酸之蛋白質,因此較容易消化。在具有蛋白敏感或過敏之人中,與過敏或敏感有關之免疫系統往往導致皮膚、呼吸道或胃腸道症狀,諸如嘔吐及腹瀉。對完整蛋白質配方表現出反應的人們往往不會對水解蛋白配方有反應,因為他們的免疫系統不會把水解蛋白視為導致他們的症狀之完整蛋白質。
一些麥膠蛋白(gliadin)及牛酪蛋白可能共有能被抗麥膠蛋白IgA抗體辨識之抗原決定部位。因此,本揭示內容之營養組成物可藉由提供包含水解蛋白(諸如水解之乳清蛋白及/或水解之酪蛋白)的蛋白質組分來降低食物過敏(諸如,例如蛋白質過敏)之發生率,從而降低一些患者對蛋白質(諸如牛酪蛋白)之免疫反應。水解蛋白組分含有比完整蛋白質組分少的過敏性抗原決定部位。
因此,於一些實施態樣中,營養組成物之蛋白質組分包含部分或高度水解之蛋白質,諸如來自牛乳之蛋白質。水解蛋白可以酶處理以分解一些或大部分引起不
良症狀之蛋白質,以減少過敏反應、不耐性和敏感。再者,蛋白質可藉由本技術領域中已知之任何方法進行水解。
本文中,術語“蛋白質水解產物”或“水解蛋白”可互換使用且係指水解蛋白,其中水解程度可為約20%至約80%,或約30%至約80%,或甚至為約40%至約60%。水解程度係指肽鍵被水解方法所破壞之程度。用於定性營養組成物之水解蛋白組分之蛋白質水解程度可由調配物技藝中之一般技術人士經由定量所選定之調配物中之蛋白質組分的胺基氮對總氮之比例(AN/TN)而很容易地測定。該胺基氮組分係藉由用於測定胺基氮含量之USP滴定法定量,而該總氮組分係藉由Tecator Kjeldahl法測定,所有這些方法均為分析化學技藝中之一般技術人員所熟知的方法。
當藉由酶催化性水解打斷蛋白質中之肽鍵時,每打斷一肽鍵會釋出一個胺基,造成胺基氮增加。應注意的是,即使是非水解蛋白亦會含有一些裸露之胺基。水解蛋白亦將具有與形成彼等之非水解蛋白不同的分子量分佈。水解蛋白之功能和營養性能可能受不同大小之肽類影響。分子量變化形廓(profile)通常係經由列出特定範圍(例如2000至5000道耳吞,大於5,000道耳吞)之分子量(以道耳吞(Dalton)計)部分的重量百分比而獲得。
如前述者,表現出對全蛋白或完整蛋白質敏感的人可受益於攝取含有水解蛋白之營養配方。這類敏感
的人可能特別受益於攝取低敏配方。
於一些實施態樣中,本揭示內容之營養組成物實質上不含完整蛋白質。在本文中,術語“實質上不含”意指本文之實施態樣包含之完整蛋白質的濃度足夠低,從而使該配方成為低敏性。根據本揭示內容之營養組成物實質上不含完整蛋白質,從而為低敏性的程度係藉由美國兒科學會2000年8月之政策聲明(August 2000 Policy Statement of the American Academy of Pediatrics)確定,其中係將低敏配方定義為當在預定隨機、雙盲,安慰劑對照之試驗中將此配方給予被確定為對牛奶過敏的嬰兒或兒童時,其在適當之臨床研究中顯示出在95%信賴水準下不會在90%之已確定為對牛奶過敏的嬰兒或兒童中引發反應。
具有食物過敏及/或乳蛋白過敏之小兒個體(諸如嬰兒)之另一種選擇為以胺基酸為基礎之不含蛋白質的營養組成物。胺基酸為蛋白質之基本建構單位。經由完全預先消化蛋白質以將蛋白質打破成其基本的化學結構使得以胺基酸為底質之配方成為可用之致敏性最低配方。
於一特定之實施態樣中,營養組成物不含蛋白質且含有游離胺基酸作為蛋白質等效來源。於此實施態樣中,胺基酸可包括,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、天冬醯胺、天冬胺酸、麩胺酸、麩醯胺酸、甘胺酸、脯胺酸、絲胺
酸、肉鹼、牛磺酸及彼等之混合物。於一些實施態樣中,胺基酸可為支鏈胺基酸。於其他實施態樣中,小胺基酸肽類可被包含在營養組成物中作為蛋白質組分。這類小胺基酸肽類可為天然產生或合成的。在營養組成物中之游離胺基酸的量可在約1至約5g/100kcal之間變化。於一實施態樣中,100%之該游離胺基酸具有小於500道耳吞之分子量。於本實施態樣中,營養調配物可為低敏性。
於營養組成物之一特定的實施態樣中,蛋白質來源之乳清:酪蛋白比類似於在人類母乳中所發現者。於一實施態樣中,蛋白質來源包含約40%至約85%之乳清蛋白及約15%至約60%之酪蛋白。
於一些實施態樣中,每100kcal營養組成物包含至多約7g/100kcal之蛋白質及/或蛋白質等效來源,於某些實施態樣中,包含介於約1g和約7g之間的蛋白質及/或蛋白質等效來源(不包括乳鐵蛋白,當存在時)。於其他實施態樣中,每100kcal之營養組成物包含介於約3.5g和約4.5g之間的蛋白質或蛋白質等效來源。
於一些實施態樣中,營養組成物包含至少一種碳水化合物來源。合適之碳水化合物來源可為任何本技藝中所使用者,例如乳糖、葡萄糖、果糖、玉米糖漿固體、麥芽糊精(maltodextrin)、蔗糖、澱粉、米漿固體及類似物。在營養組成物中之碳水化合物組分的量為至少約5g/100kcal,通常可在介於約5g/100kcal和約25g/100kcal之間變化。於一些實施態樣中,碳水化合物之量係介於約
6g和約22g/100kcal之間。於其他實施態樣中,碳水化合物之量係介於約12g和約14g/100kcal之間。於一些實施態樣中,玉米糖漿固體為較佳者。再者,最好在營養組成物中包含水解、部分水解及/或高度水解之碳水化合物,因為它們容易消化。具體而言,水解之碳水化合物較不可能含有過敏性抗原結合部位。
適合用於本揭示內容之碳水化合物物質的非限制性實例包括水解的或完整的、天然或經化學改質之來自玉米、木薯(tapioca)、稻米或馬鈴薯之糯質或非糯質形式的澱粉。合適之碳水化合物的非限制性實例包括各種被稱為水解玉米澱粉、麥芽糊精、麥芽糖、玉米糖漿、右旋糖、玉米糖漿固體、葡萄糖及各種其他葡萄糖聚合物的水解澱粉及彼等之組合。其他合適之碳水化合物的非限制性實例包括那些通常稱為蔗糖、乳糖、果糖、高果糖玉米糖漿、難消化之寡醣(諸如果寡醣)者及彼等之組合。
於一特定之實施態樣中,營養組成物之另外的碳水化合物組分包含100%之乳糖。於另一實施態樣中,另外的碳水化合物組分包含介於約0%和60%之間的乳糖。於另一實施態樣中,另外的碳水化合物組分包含介於約15%和55%之間的乳糖。再於另一實施態樣中,另外的碳水化合物組分包含介於約20%和30%之間的乳糖。於這些實施態樣中,其餘之碳水化合物來源可為本技術領域中已知之任何碳水化合物。於一實施態樣中,碳水化合物組分包含約25%之乳糖及約75%之玉米糖漿固體。
於某些實施態樣中,營養組成物亦可含有一或多種益菌素(亦稱為益菌素組分)。益菌素發揮健康利益,此健康利益可包括,但不限於選擇性刺激一或有限數量之有益的腸道細菌之生長及/或活性、刺激攝入之益生菌微生物的生長及/或活性、選擇性減少腸道病原體及有利地影響腸道短鏈脂肪酸之變化形廓(profile)。這類益菌素可為天然產生的、合成的或透過有機體及/或植物之遺傳工程操作研發,無論這類新來源為現在已知的或稍後研發的。可用於本揭示內容中之益菌素可包括寡醣、多醣及其他含有果糖、木糖(xylose)、大豆、半乳糖、葡萄糖及甘露糖(mannose)之益菌素。
更具體地,用於本揭示內容中之益菌素可包括聚右旋糖、聚右旋糖粉、乳酮糖(lactulose)、乳果寡醣(lactosucrose)、棉籽糖(raffinose)、葡萄寡醣、菊糖(inulin)、果寡醣、異麥芽寡醣、大豆寡醣、乳果糖、木寡醣、殼寡醣(chito-oligosaccharide)、甘露寡醣、阿拉伯寡醣、唾液酸寡醣、岩藻寡醣(fuco-oligosaccharide)、半乳寡醣及龍膽寡醣(gentio-oligosaccharide)。
於一實施態樣中,存在於營養組成物中之益菌素總量可為組成物之約1.0g/L至約10.0g/L。更佳地,存在於該營養組成物中之益菌素總量可為組合物之約2.0g/L至約8.0g/L。於一些實施態樣中,存在於營養組成物中之益菌素總量可為約0.01g/100kcal至約0.15g/100kcal。於某些實施態樣中,存在於營養組成物中
之益菌素總量可為約0.03g/100kcal至約0.07g/100kcal。再者,營養組成物可包含含有PDX之益菌素組分。於一些實施態樣中,益菌素組分包含至少20% w/w之PDX、GOS或彼等之混合物。
若益菌素組成物中使用PDX,於一實施態樣中,營養組成物中之PDX的量可在約0.015g/100kcal至約0.15g/100kcal的範圍內。於另一實施態樣中,PDX的量可在約0.02g/100kcal至約0.06g/100kcal的範圍內。於一些實施態樣中,包含在營養組成物中之PDX的量可為足以提供約1.0g/L至10.0g/L之PDX。於另一實施態樣中,營養組成物含有約2.0g/L至8.0g/L之PDX量。再於其他實施態樣中,營養組成物中之PDX量可為約0.015g/100kcal至約0.05g/100kcal。
於其他實施態樣中,益菌素組分可包含GOS。於一實施態樣中,若益菌素組成物中使用GOS,營養組成物中之GOS的量可為約0.015g/100kcal至約0.15g/100kcal。於另一實施態樣中,營養組成物中之GOS的量可為約0.02g/100kcal至約0.05g/100kcal。於其他實施態樣中,營養組成物中之GOS的量可為約0.015g/100kcal至約0.1g/100kcal或約0.01mg/100kcal至約0.05mg/100kcal。
於本發明之一特定實施態樣中係將PDX與GOS一起投予。
於另一實施態樣中係將總量為至少約0.02
g/100kcal、或約0.02g/100kcal至約0.15mg/100kcal之GOS和PDX補充入營養組成物中。於一些實施態樣中,營養組成物可包含總量為約0.06至約0.08mg/100kcal之GOS和PDX。
如上述,本揭示內容之營養組成物亦可包含乳鐵蛋白。乳鐵蛋白為約80kD之單鏈多肽,其根據物種含有1-4個聚醣(glycan)。不同物種之乳鐵蛋白的3-D結構非常相似,但不完全相同。各乳鐵蛋白包含兩個同源小葉,稱為N-及C-小葉,其分別指該分子之N-端和C-端部分。各小葉進一步由兩個形成裂縫之子葉或結構域(domain)所組成,三價鐵離子(Fe3+)被緊密鍵合在此裂縫中,與碳酸(氫)根陰離子協同合作。這些結構域分別稱為N1、N2、C1及C2。乳鐵蛋白之N端具有負責許多重要的結合特性之強陽離子肽區。乳鐵蛋白具有非常高之等電點(~pI9)且其陽離子性質在其防禦細菌、病毒及真菌病原體的能力中扮演主要角色。在乳鐵蛋白之N-端區內有幾個陽離子性胺基酸殘基簇,它們介導該乳鐵蛋白對抗多種微生物之生物活性。例如,人乳鐵蛋白之N-端殘基1至47(牛乳鐵蛋白之1至48)對乳鐵蛋白之不依附鐵的生物活性而言至為重要。在人乳鐵蛋白中,殘基2至5(RRRR)及28至31(RKVR)為N端中富含精胺酸之陽離子結構域,其對乳鐵蛋白之抗微生物活性特別重要。在牛乳鐵蛋白之N端可找到類似區域(殘基17至42;FKCRRWQWRMKKLGAPSITCVRRAFA)。
如出現在刊物BIOCHEMISTRY AND CELL BIOLOGY,pp275-281(2006)中之"Perspectives on Interactions Between Lactoferrin and Bacteria"中之描述,來自不同宿主物種之乳鐵蛋白的胺基酸序列可有不同變化,雖然其普遍具有相當高之等電點且在內葉之終端區具有帶正電荷之胺基酸。用於本揭示內容之合適的非人乳鐵蛋白包括,但不限於那些與人乳鐵蛋白之胺基酸序列具有至少48%之同源性者。例如,牛乳鐵蛋白(“bLF”)之胺基酸組成與人乳鐵蛋白之胺基酸組成具有約70%之序列同源性。於一些實施態樣中,非人乳鐵蛋白與人乳鐵蛋白具有至少55%之同源性,且於一些實施態樣中,具有至少65%之同源性。可接受用於本揭示內容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。
於一實施態樣中,乳鐵蛋白在營養組成物中之存在量為至少約15mg/100kcal。於某些實施態樣中,營養組成物可每100kcal包含介於約15mg和約300mg之間的乳鐵蛋白。於其中該營養組成物為嬰兒配方之另一實施態樣中,該營養組成物可每100kcal包含約60mg至約150mg之乳鐵蛋白;再於另一實施態樣中,該營養組成物可每100kcal包含約60mg至約100mg之乳鐵蛋白。
於一些實施態樣中,營養組成物可每毫升配方包括含量約0.5mg至約1.5mg之乳鐵蛋白。於替代人乳之營養組成物中,每毫升配方中之乳鐵蛋白的存在量可為
約0.6mg至約1.3mg。於某些實施態樣中,營養組成物可每升包含約0.1至約2克之乳鐵蛋白。於一些實施態樣中,營養組成物可每升配方包括約0.6至約1.5克之乳鐵蛋白。
用於某些實施態樣中之bLF可為自全乳中分離出及/或具有低體細胞數之任何bLF,其中“低體細胞數”係指體細胞數少於200,000細胞/mL。舉例而言,合適之bLF可從紐西蘭Morrinsville之Tatua Co-operative Dairy Co.Ltd.、荷蘭Amersfoort之FrieslandCampina Domo或紐西蘭Auckland之Fonterra Co-Operative Group Limited取得。
用於本揭示內容之乳鐵蛋白可為,例如從非人類之動物的乳汁分離出或由基改有機體製造。例如,在美國專利第4,791,193號(其全文以引用方式納入本文)中,Okonogi等人揭示用於製造高純度之牛乳鐵蛋白的方法。一般而言,所揭示之過程包括三個步驟。先將生乳材料與弱酸性陽離子交換劑接觸以吸附乳鐵蛋白,再進行第二步驟,在此步驟中進行清洗以將未被吸附之物質除去。接著為去吸附步驟,在此步驟中移除乳鐵蛋白以製造純化之牛乳鐵蛋白。其他方法可包括如美國專利第7,368,141、5,849,885、5,919,913和5,861,491號(其全文以引用方式納入本文)中所描述之步驟。
於某些實施態樣中,用於本揭示內容中之乳鐵蛋白可藉由用於從乳汁來源分離出蛋白質之擴張床吸附
(expanded bed adsorption)(“EBA”)製程提供。EBA,有時亦稱為穩定流化床吸附,為一種用於從乳汁來源分離出乳蛋白(諸如乳鐵蛋白)之製程,其包含:建立包含微粒基質之擴張床吸附管柱,將乳汁來源施加至該基質,並以包含約0.3至約2.0M之氯化鈉的洗提緩衝液將乳鐵蛋白從基質洗提出。任何哺乳動物乳汁來源均可用於本揭示內容之製程中,雖然於特定之實施態樣中,乳汁來源為牛乳來源。於一些實施態樣中,該乳汁來源包含全乳、低脂乳、脫脂乳、乳清、酪蛋白或彼等之混合物。
於特定之實施態樣中,標的蛋白為乳鐵蛋白,雖然亦可分離出其他乳蛋白,諸如乳過氧化酶(lactoperoxidase)或乳白蛋白(lactalbumin)。於一些實施態樣中,製程包含下列步驟:建立包含微粒基質之擴張床吸附管柱,將乳汁來源施加至該基質,並以約0.3至約2.0M之氯化鈉將乳鐵蛋白從基質洗提出。於其他實施態樣中,以約0.5至約1.0M之氯化鈉將乳鐵蛋白洗提出,而於另外之實施態樣中,以約0.7至約0.9M之氯化鈉將乳鐵蛋白洗提出。
該擴張床吸附管柱可為本技術領域中已知之任一者,諸如美國專利案第7,812,138、6,620,326及6,977,046號(其內容以引用方式被併入本文)中所描述者。於一些實施態樣中,乳汁來源被施加至擴張模式之管柱中,且該洗提係以擴張或壓縮(packed)模式進行。於特定之實施態樣中,該洗提係以擴張模式進行。例如,擴張模
式中之擴張比可為約1至約3、或約1.3至約1.7。EBA技術進一步描述於國際公開申請案第WO 92/00799、WO 02/18237、WO 97/17132號(其全文以引用方式納入本文)中。
乳鐵蛋白之等電點為約8.9。先前之分離乳鐵蛋白的EBA方法係使用200mM氫氧化鈉作為洗提緩衝液。因此,該系統之pH值上升超過12,而該乳鐵蛋白之結構和生物活性可能被不可逆之結構變化危害。現已發現,氯化鈉溶液可作為從EBA基質分離出乳鐵蛋白之洗提緩衝液。於某些實施態樣中,氯化鈉之濃度為約0.3M至約2.0M。於其他實施態樣中,乳鐵蛋白洗提緩衝液之氯化鈉濃度為約0.3M至約1.5M,或約0.5M至約1.0M。
本揭示內容之營養組成物亦含有另外的LCPUFA來源,亦即,SDA和GLA以外之LCPUFA來源,尤其是包含二十二碳六烯酸之LCPUFA來源。其他合適之LCPUFA包括,但不限於α-亞麻油酸、γ-亞麻油酸、亞麻油酸、二十碳五烯酸(EPA)及花生四烯酸(ARA)。
於一實施態樣中,特別是若該營養組成物為嬰兒配方時,該營養組成物係補充DHA和ARA二者。於此實施態樣中,ARA:DHA之重量比可介於約1:3和約9:1之間。於一特定之實施態樣中,ARA:DHA之比為約1:2至約4:1。
有利的是,在營養組成物中之非SDA和GLA
長鏈多不飽和脂肪酸的量為至少約5mg/100kcal,且可在約5mg/100kcal至約100mg/100kcal之間變化,更佳為約10mg/100kcal至約50mg/100kcal。
營養組成物可使用本技術領域中已知之標準技術補充含有DHA及/或ARA之油。例如,可經由以DHA及ARA取代等量之通常存在於該組成物中的油(諸如高油酸葵花油)來將DHA及ARA加入組成物中。另一實例為以含有DHA和ARA之油取代等量之通常存在於不含DHA和ARA之組成物中的總脂肪摻合物之其餘部分來將該含有DHA和ARA之油添加到組成物中。
若使用DHA及/或ARA來源時,該DHA及/或ARA來源可為本技術領域中已知之任何來源,諸如海洋生物油、魚油、單細胞油、蛋黃脂質及腦脂質。於一些實施態樣中,DHA和ARA係源自單細胞Martek油、DHASCO®及ARASCO®或彼等之多種變化。DHA和ARA可為天然形式,惟LCPUFA來源的其餘部分不會對嬰兒造成任何實質的不良影響。或者,可使用精製形式之DHA和ARA。
於一實施態樣中,DHA和ARA之來源為如美國專利第5,374,567;5,550,156;及5,397,591號(其揭示內容全文以引用方式併入本文)中所教示之單細胞油。然而,本揭示內容並不僅限於該類油。
此外,營養組成物之一些實施態樣可模擬人類母乳之某些特性。然而,為了滿足一些個體的特定營養
需求,營養組成物所包含之某些營養成分的量可較人乳所含有者更多。例如,營養組成物所包含之DHA的量可較人類母乳所包含者更多。因此,營養組成物中所增加之DHA的量可以彌補現有之DHA的營養不足。
上述之營養素的選擇被認為可對嬰兒和兒童提供具有不能從現有的產品取得之新穎利益之綜合性套組。首先,攝取此種以乳為底質的營養組成物可改善眼睛的發育及涉及認知、記憶、學習、情緒調節和動作協調之腦部區域的功能和發展。在那些腦部區域中之該類生理變化可直接解釋已被發現的益處。第二,PDX和GOS之組合可以改變中樞神經系統(“CNS”)內之生物胺和神經傳導物質的製造,且該類變化可以解釋餵食PDX/GOS對社交技巧、焦慮和記憶功能的有益效果。第三,乳鐵蛋白之新穎效果可改善對壓力情況的適應力,並分別提高學習能力,此為與其他組分不同的獨特屬性。總之,此營養組成物可藉由修飾腸道微生物相、改善眼睛的發育、優化腦部組成及改善各種與腦部相關的行為和功能而在嬰兒和兒童期扮演重要的角色。
咸信,所揭示之營養組成物中之營養素的獨特組合能夠提供嬰兒和兒童新穎且意想不到之與腦部相關的益處。再者,此營養組成物之益處被認為係在嬰兒期取得,亦可在兒童及其腦部持續生長和發育時將此營養組成物納入作為多樣化飲食之一部分來獲得益處。
投予小兒個體包含SDA與益菌素(尤其是
PDX和GOS)、來自非人來源之乳鐵蛋白及其他LCPUFA之營養組成物具有多種目的,這些目的之組合目前沒有描述或提供:使整體配方之組成和功能更接近人乳;解決特定之嬰兒和兒童營養缺口;改善嬰兒和兒童的微生物菌群(需要或不需要益生菌);提高特定之腦部功能,諸如(但不限於)記憶功能、學習能力、社交技巧、減少焦慮、視力、運作技能、手眼協調、一般煩躁(降低內臟疼痛敏感性)、睡眠品質;增進多種營養素(諸如維生素B)之生物可利用性、及優化腦部發育和功能的相關利益;及調節/優化腦部組成,以透過調節CNS神經傳導物質來增進CNS內及CNS與腸道之間的聯繫。咸信,進一步添加GLA可提供更為改善的結果。
於一些實施態樣中,營養組成物進一步包含唾液酸。唾液酸為具有50名成員以上之9碳糖家族,其均為神經胺酸(neuroaminic acid)衍生物。人體中所發現之主要的唾液酸家族係來自N-乙醯神經胺酸亞族。唾液酸係在乳汁中找到,諸如牛乳和羊乳。在哺乳動物中,與其他體細胞膜相比較,神經細胞膜所具有之唾液酸濃度最高。唾液酸殘基亦為神經節苷脂(ganglioside)的組分。
若營養組成物中包含唾液酸,唾液酸之存在量為約0.5mg/100kcal至約45mg/100kcal。於一些實施態樣中,唾液酸之存在量可為約5mg/100kcal至約30mg/100kcal。再於其他實施態樣中,唾液酸之存在量可為約10mg/100kcal至約25mg/100kcal。
於一實施態樣中,營養組成物可含有一或多種益生菌。本實施態樣中可接受本技術領域中已知之任何益生菌。於一特定之實施態樣中,益生菌可選自下列中之任一者:乳酸桿菌種(Lactobacillus species)、雷曼氏乳桿菌GG(Lactobacillus rhamnosus GG)(ATCC編號53103)、比菲德氏菌種(Bifidobacterium species)、長比菲德氏菌BB 536(Bifidobacterium longum BB 536)(BL999,ATCC:BAA-999)、長比菲德氏菌AH1206(NCIMB:41382)、短比菲德氏菌AH1205(Bifidobacterium breve AH1205)(NCIMB:41387)、嬰兒比菲德氏菌35624(Bifidobacterium infantis 35624)(NCIMB:41003)及動物比菲德氏菌乳酸亞種BB-12(Bifidobacterium animalis subsp.lactis BB-12)(DSM編號10140)或彼等之任何組合。
若包含在組成物中,益生菌之量可在每100kcal中含有約1×104至約1.5×1012菌落形成單位(cfu)的益生菌之間變化。於某些實施態樣中,每100kcal含有約1×106至約1×109cfu之益生菌。於某些其他實施態樣中,益生菌之量可在每100kcal含有約1×107cfu/100kcal至約1×108cfu/100kcal之間變化。
於一實施態樣中,益生菌可為存活的或非存活的。如本文所使用之術語“存活的”係指活的微生物。術語“非存活的”或“非存活的益生菌”係指無法存活之益生菌微生物、彼等之細胞組分及/或彼等之代謝物。這類非存活的益生菌可能已經加熱滅殺或以其他方式滅活,
但其保留能有利地影響宿主健康的能力。可用於本揭示內容中之益生菌可為天然產生的、合成的或透過有機體之遺傳工程操作研發的,無論這類來源為現在已知的或稍後發展的。
於一些實施態樣中,營養組成物可包括含有益生菌細胞同等物的來源,此係指相當於相等數目之存活細胞的非存活、非複製型益生菌的量。術語“非複製型”應被理解為從相同量之複製型細菌取得之非複製型微生物(包括滅活之益生菌、DNA片段、細胞壁或細胞質化合物)的量(cfu/g)。換言之,該非活著、非複製型有機體之量係如同所有該微生物均為存活般,以cfu表示,不論他們是否為死亡、非複製型、經滅活、片段的,等。當營養組成物中包含非存活之益生菌時,該益生菌細胞同等物的量可在每100kcal含有約1×104至約1.5×1010之益生菌細胞同等物之間變化。於一些實施態樣中,益生菌細胞同等物之量可為每100kcal營養組成物中含有約1×106至約1×109之益生菌細胞同等物。於某些其他實施態樣中,益生菌細胞同等物之量可在每100kcal營養組成物中含有約1×107至約1×108之益生菌細胞同等物之間變化。
於一些實施態樣中,被納入營養組成物中之益生菌來源可包含存活之菌落形成單位及非存活之細胞同等物二者。
於一些實施態樣中,營養組成物包含來自益生菌分批培養製程之後期指數生長期的培養上清液,如國
際公開申請案第WO 2013/142403號(其全文以引用方式納入本文)中所揭示者。不欲受理論之束縛,咸信,該培養上清液之活性可歸因於被發現在益生菌之分批培養的後期指數(或“對數(log”)期釋入培養基中之組份的混合物(包括蛋白質性(proteinaceous)物質,且可能包括(胞外)多醣物質)。如本文所使用之術語“培養上清液”包括在培養基中所發現之組分的混合物。菌之分批培養中所認定之階段為熟習本技藝之人士所已知。這些階段為“停滯(lag)”、“對數(log)”(“對數(logarithmic)”或“指數(exponential)”)及“靜止(stationary)”和“死亡(death)”(或“對數下降(logarithmic decline)”)期。在存有活菌期間的所有時期中,該菌代謝來自培養基之營養素並分泌(施加、釋出)物質入培養基中。在生長階段之指定時點所分泌出之物質的組成一般而言是無法預測的。
於一實施態樣中,培養上清液可藉由包含以下步驟之製程取得:(a)使用分批製程將益生菌,諸如LGG培養在合適之培養基中;(b)在培養步驟之後期指數生長期收穫該培養上清液,該後期指數生長期之界定係參考介於該分批培養製程之停滯期和靜止期之間的後半段時間;(c)隨意地從該上清液移除低分子量成分,以保留分子量大於5至6千道耳吞(kDa)之成分;(d)從該培養上清液移除液體內容物,從而取得該組成物。
培養上清液可包含從後期指數期收穫之分泌物質。後期指數期係發生在中期指數期(其為指數期之期
間之一半時間,因此,所指之後期指數期係指介於停滯期和靜止期之間的後半段時間)後之時間。尤其是,本文所使用之術語“後期指數期”係指LGG分批培養製程中介於停滯期和靜止期之間的後四分之一時間部分。於一些實施態樣中係在指數期之期間的75%至85%之時間點收穫該培養上清液,且可在指數期約經過六分之五的時間收穫。
如所指出者,所揭示之營養組成物可包含β-葡聚醣之來源。葡聚醣(glucan)為多醣類,具體地說為葡萄糖之聚合物,其為天然產生且可在細菌、酵母菌、真菌及植物之細胞壁中找到。乙型葡聚醣(β-葡聚醣)本身為葡萄糖聚合物的不同子集,其係由經由β型糖苷鍵鏈接在一起之葡萄糖單體鏈所組成以形成複合碳水化合物。
β-1,3-葡聚醣為從,例如酵母菌、蕈、細菌、藻類或穀純化之碳水化合物聚合物。(Stone BA,Clarke AE.Chemistry and Biology of(1-3)-Beta-Glucans.London:Portland Press Ltd;1993。)β-1,3-葡聚醣之化學結構係取決於該β-1,3-葡聚醣之來源。再者,各種理化參數(諸如溶解度、一級結構、分子量及分支)在β-1,3-葡聚醣之生物活性中具有作用(Yadomae T.,Structure and biological activities of fungal beta-1,3-glucans.Yakugaku Zasshi.2000;120:413-431。)
β-1,3-葡聚醣為帶有或不帶有β-1,6-葡萄糖側鏈之天然多醣,其可在各種植物、酵母菌、真菌及細菌
之細胞壁中發現。β-1,3;1,6-葡聚醣為那些包含帶有(1,3)鏈接之葡萄糖單元者,其具有連接在位置(1,6)處之側鏈。β-1,3;1,6-葡聚醣為一群分享結構共性(包括藉由β-1,3鍵連接之直鏈葡萄糖單元骨幹,其帶有從此骨幹延伸之經β-1,6連接之葡萄糖分支)的葡萄糖聚合物的異質族群。雖然這是目前描述之β-葡聚醣類別的基本結構,其中可能存有一些變化。例如,某些酵母菌β-葡聚醣具有從β(1,6)分支延伸之其他β(1,3)分支區,這進一步增加其各別結構之複雜性。
源自麵包酵母(釀酒酵母(Saccharomyces cerevisiae))之β-葡聚醣係由連接在位置1和3之D-葡萄糖分子的鏈所組成,其具有連接在位置1和6處之葡萄糖側鏈。源自酵母菌之β-葡聚醣為具有葡萄糖單元之直鏈的一般結構的不溶性、纖維狀複糖,此結構具有β-1,3骨幹,其間穿插長度通常為6-8個葡萄糖單元之β-1,6側鏈。更具體地說,源自麵包酵母之β-葡聚醣為聚-(1,6)-β-D-葡哌喃糖苷基-(1,3)-β-D-葡哌喃糖。
此外,β-葡聚醣之耐受性良好且不會在小兒個體內產生或引起過量氣體、腹脹(abdominal distension)、脹氣(bloating)或腹瀉。在用於小兒個體之營養組成物(諸如嬰兒配方、成長乳或其他兒童營養產品)中添加β-葡聚醣將可藉由增加對抗入侵病原體的抗性來改善個體之免疫反應,從而維持或改善整體健康。
本揭示內容之營養組成物包含β-葡聚醣。於
一些實施態樣中,β-葡聚醣為β-1,3;1,6-葡聚醣。於一些實施態樣中,β-1,3;1,6-葡聚醣係源自麵包酵母。營養組成物可包含全葡聚醣顆粒β-葡聚醣、微粒β-葡聚醣、PGG-葡聚醣(聚-1,6-β-D-葡哌喃糖苷基-1,3-β-D-葡哌喃糖),或彼等之任何混合物。
於一些實施態樣中,存在於組成物中之β-葡聚醣的量為每100g組成物中包含約0.010至約0.080g之β-葡聚醣。於其他實施態樣中,每份用量之營養組成物包含約10至約30mg之β-葡聚醣。於另一實施態樣中,每8fl.Oz.(236.6ml)用量之營養組成物包含約5至約30mg之β-葡聚醣。於其他實施態樣中,營養組成物所包含之β-葡聚醣量足以提供每天約15mg至約90mg之β-葡聚醣。營養組成物可以數個劑量內投遞以達成在一整天內將目標量之β-葡聚醣投遞予個體。
於一些實施態樣中,營養組成物中之β-葡聚醣的量為每100kcal包含約3mg至約17mg之β-葡聚醣。於另一實施態樣中,β-葡聚醣之量為每100kcal包含約6mg至約17mg之β-葡聚醣。
營養組成物中亦可添加一或多種維生素及/或礦物質,其量為足以提供個體之每日營養需求。本技藝之一般技術人士應理解維生素及礦物質之需求將根據,例如兒童的年齡而有所不同。例如,嬰兒之維生素和礦物質需求可能與年齡介於1至13歲之間的兒童不同。因此,本實施態樣並不欲將營養組成物限制在特定之年齡組,而是
提供可接受之維生素和礦物質組分的範圍。
營養組成物可隨意性地包括,但不限於一或多種下列維生素或彼等之衍生物:維生素B1(噻胺(thiamin)、噻胺二磷酸酯TPP、三磷酸噻胺TTP、噻胺鹽酸鹽、單硝酸噻胺素)、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、核黃素(lactoflavin)、卵黃素(ovoflavin))、維生素B3(菸鹼(niacin)、菸鹼酸(nicotinic acid)、菸鹼醯胺(nicotinamide)、3-吡啶甲醯胺(niacinamide)、菸鹼醯胺腺嘌呤二核苷酸NAD、菸鹼酸單核苷酸NicMN、吡啶-3-羧酸)、維生素B3先質色胺酸、維生素B6(吡哆醇(pyridoxine)、吡哆醛(pyridoxal)、吡哆胺(pyridoxamine)、鹽酸吡哆醇)、泛酸(泛酸鹽、泛醇(panthenol))、葉酸鹽(葉酸、葉酸素(folacin)、蝶醯麩胺酸(pteroylglutamic acid))、維生素B12(鈷胺素(cobalamin)、甲鈷胺素、去氧腺苷鈷胺素、氰鈷胺素、羥鈷胺素、腺苷鈷胺素)、生物素、維生素C(抗壞血酸)、維生素A(視黃醇(retinol)、醋酸視黃酯(retinyl acetate)、棕櫚酸視黃酯(retinyl palmitate)、具其他長鏈脂肪酸之視黃酯、視黃醛(retinal)、視黃酸(retinoic acid)、視黃醇酯)、維生素D(骨化醇(calciferol)、膽骨化醇(cholecalciferol)、維生素D3、1,25-二羥基維生素D)、維生素E(α-生育酚(α-tocopherol)、α-生育酚醋酸酯、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(phylloquinone)、萘醌(naphthoquinone)、維生素K2、甲萘醌(menaquinone)-7、維生素K3、甲萘醌-4、萘酚醌(menadione)、甲萘醌-8、甲萘醌-8H、甲萘醌-9、甲萘醌-9H、甲萘醌-10、甲萘醌-11、甲萘醌-12、甲萘醌-13)、膽鹼、肌醇、β-胡蘿蔔素及彼等之任何組合。
此外,營養組成物可隨意地包括,但不限於一或多種下列礦物質或彼等之衍生物:硼、鈣、醋酸鈣、葡萄糖酸鈣、氯化鈣、乳酸鈣、磷酸鈣、硫酸鈣、氯化物、鉻、氯化鉻、吡啶甲酸鉻(chromium picolonate)、銅、硫酸銅(copper sulfate)、葡萄糖酸銅、五水合硫酸銅(cupric sulfate)、氟化物、鐵、羰基鐵、三價鐵、富馬酸亞鐵、正磷酸亞鐵、研磨鐵(iron trituration)、多醣鐵、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、醋酸鉀、硒、硫、鈉、多庫酯鈉(docusate sodium)、氯化鈉、硒酸鈉、鉬酸鈉、鋅、氧化鋅、硫酸鋅及彼等之混合物。礦物質化合物之非限制性示例衍生物包括任何礦物質化合物之鹽、鹼鹽、酯和螯合物。
礦物質可以鹽之形式(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、五水合硫酸銅、硫酸錳及亞硒酸鈉)被添加在營養組成物中。另外之維生素和礦物質可依本技術領域所知者添加。
於一實施態樣中,每一份量營養組成物中所含有之維生素A、C和E、鋅、鐵、碘、硒和膽鹼的量為對任何指定國家之最大飲食建議量的約10至約50%,或對國家群組之平均飲食建議量的約10至約50%。於另一實施態樣中,每一份量之兒童營養組成物可供應之維生素B量為對任何指定國家之最大飲食建議量的約10至30%,或對國家群組之平均飲食建議量的約10至30%。再於另一實施態樣中,兒童營養產品中之維生素D、鈣、鎂、磷及鉀的含量可相當於乳品中所發現者之平均含量。於其他實施態樣中,每一份量之兒童營養組成物中的其他營養素之存在量可為對任何指定國家的最大飲食建議量之約20%,或對國家群組之平均飲食建議量的約20%。
本揭示內容之營養組成物可隨意地包括一或多種下列調味劑,包括,但不限於調味之萃取物、揮發油、可可亞或巧克力調味劑、花生醬調味劑、餅乾碎片、香草或任何市售之調味劑。有用之調味劑的實例包括,但不限於純茴香萃取物、仿香蕉萃取物、仿櫻桃萃取物、巧克力萃取物、純檸檬萃取物、純柳橙萃取物、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;或揮發油,諸如香蜂草油(balm oil)、月桂油、佛手柑油(bergamot oil)、柏木油(cedarwood oil)、櫻桃油、肉桂油、丁香油或薄荷油;花生醬、巧克力調味劑、香草餅乾碎片、奶油糖果、太妃糖及彼等之混合物。調味劑的量可根據所使用之調味劑而有很大的變
化。調味劑之類型和量可依本技藝所已知者選擇。
本揭示內容之營養組成物可隨意地包括一或多種添加以用來穩定該最終產品之乳化劑。合適之乳化劑的實例包括,但不限於卵磷脂(lecithin)(例如來自卵或大豆)、α-乳白蛋白及/或單酸甘油酯和二酸甘油酯,和彼等之混合物。其他乳化劑對熟習本技藝之人士而言是明顯的,而合適之乳化劑的選擇將部分取決於調配物及最終產品。
本揭示內容之營養組成物可隨意地包含一或多種亦可添加在其中以延長產品之儲存壽命的防腐劑。合適之防腐劑包括,但不限於山梨酸鉀、山梨酸鈉、苯甲酸鉀、苯甲酸鈉、EDTA二鈉鈣及彼等之混合物。
本揭示內容之營養組成物可隨意地包括一或多種穩定劑。用於實行本揭示內容之營養組成物的合適穩定劑包括,但不限於阿拉伯膠、印度樹膠(gum ghatti)、刺梧桐樹膠(gum karaya)、黃蓍膠(tragacanth gum)、瓊脂、紅藻膠(furcellaran)、果阿膠(guar gum)、結冷膠(gellan gum)、刺槐豆膠(locust bean gum)、果膠(pectin)、低甲氧基果膠、明膠、微晶型纖維素、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(單酸甘油酯及二酸甘油酯之二乙醯基酒石酸酯)、右旋糖苷、角叉菜膠(carrageenan)及彼等之混合物。
所揭示之營養組成物可以本技術領域中已知之任何形式提供,諸如粉劑、凝膠、懸浮液、糊劑、固
體、液體、液體濃縮物、可重構成之奶粉替代品或即時使用之產品。於某些實施態樣中,營養組成物可包含營養補充劑、兒童營養產品、嬰兒配方、人乳強化劑、成長乳或任何其他設計以用於嬰兒或小兒個體之營養組成物。本揭示內容之營養組成物包括,例如經口食入、促進健康之物質,包括,例如食品、飲料、片劑、膠囊和粉劑。再者,本揭示內容之營養組成物可經標準化成特定之卡路里含量,其可以即時使用之產品形式提供,或可以濃縮形式提供。於一些實施態樣中,營養組成物為粉劑形式,其顆粒大小係在5μm至1500μm之範圍內,更佳為在10μm至300μm之範圍內。
若營養組成物為即時使用之產品的形式,營養組成物之滲透壓濃度(osmolality)可為介於約100至約1100mOsm/kg水之間,更常為約200至約700mOsm/kg水。
本揭示內容之營養組成物可提供最低限度、部分或全部之營養支持。組成物可為營養補充劑或代餐。組成物可為,但不必須是營養完整的。於一實施態樣中,本揭示內容之營養組成物為營養完整的且含有合適類型和量之脂質、碳水化合物、蛋白質、維生素和礦物質。脂質或脂肪之量通常可在約1至約7g/100kcal之間變化。蛋白質之量通常可在約1至約7g/100kcal之間變化。碳水化合物之量通常可在約6至約22g/100kcal之間變化。
於一實施態樣中,本揭示內容之營養組成物
包含有效量之膽鹼。膽鹼為細胞之正常功能所必要的營養素。其為膜磷脂之先質,且其加速乙醯膽鹼(一種涉及記憶儲存的神經傳導物質(neurotransmitter))之合成和釋出。再者,儘管不欲受限於此理論或任何其他理論,咸信,膳食膽鹼與二十二碳六烯酸(DHA)協同作用以促進生物合成磷脂醯膽鹼,從而協助促進人類個體中之突觸生成。此外,膽鹼和DHA可展現出促進樹突棘形成之協同作用,這對維護已建立之突觸連接非常重要。於一些實施態樣中,本揭示內容之營養組成物包括有效量之膽鹼,該有效量為每8fl.oz.用量(236.6ml)包含約20mg膽鹼至每8fl.oz.用量(236.6ml)包含約100mg。
再者,於一些實施態樣中,營養組成物為營養完整的,作為個體唯一之營養來源其含有合適類型及量之脂質、碳水化合物、蛋白質、維生素及礦物質。確切地,營養組成物可隨意地包含任意數量之蛋白質、肽、胺基酸、脂肪酸、益生菌及/或彼等之代謝副產物、益菌素、碳水化合物及可提供個體許多營養和生理助益之任何其他營養素或其他化合物。此外,本揭示內容之營養組成物可包含香料、香料增强劑、甜味劑、色素、維生素、礦物質、治療成分、功能性食品成分、食品成分、加工成分或彼等之組合。
本揭示內容進一步提供用於提供個體營養支持的方法。該方法包含投予該個體有效量之本揭示內容的營養組成物。
營養組成物可直接被排入個體之腸道中。於一些實施態樣中,營養組成物係直接被排入腸道中。於一些實施態樣中,組成物可被配製成欲在醫生的監督下服用或經腸道投予且可用於疾病或病況(諸如腹腔疾病及/或食物過敏)之特定膳食管理,該疾病或病況之獨特的營養需求係基於公認之科學原則藉由醫療評估建立。
本揭示內容之營養組成物並不限於包含本文中具體表列之營養素的組成物。任何營養素均可以該組成物之一部分的形式投遞,以滿足個體之營養需求及/或優化個體之營養狀態。
於一些實施態樣中,營養組成物可從嬰兒出生開始投遞予嬰兒,直至符合足月妊娠之時間。於一些實施態樣中,可將營養組成物投遞予嬰兒,直到至少為約三個月矯正年齡。於另一實施態樣中,可將營養組成物投遞予個體,只要有必要矯正營養缺乏。再於另一實施態樣中,可將營養組成物從嬰兒出生開始投遞予嬰兒,直到至少為約六個月矯正年齡。再於另一實施態樣中,可將營養組成物從嬰兒出生開始投遞予嬰兒,直到至少約一歲矯正年齡。
本揭示內容之營養組成物可被標準化成特定之卡路里含量,其可以即時使用(ready-to-use)之產品形式提供,或者其可以濃縮之形式提供。
於一些實施態樣中,本揭示內容之營養組成物為成長乳。成長乳為欲用於1歲以上(通常為1至3
歲、4至6歲或1至6歲)之兒童的經強化之以乳為底質的飲品。其不為醫療食品,且不欲作為代餐或補充劑來解決特定之營養缺乏。相反地,成長乳之設計旨在作為多樣化飲食的補充劑,以提供兒童達到持續性每日攝入所有必需維生素和礦物質、大量營養素加額外之功能性膳食組分(諸如那些具有聲稱之促進健康性能的非必需營養素)的額外保障。
根據本揭示內容之營養組成物的確切組成在各市場之間,根據當地法規及所欲族群之膳食攝入信息可有所變化。於一些實施態樣中,根據本揭示內容之營養組成物係由乳蛋白來源(諸如全脂或脫脂乳),加上用於取得所需之感官性質之添加的糖和甜味劑,以及添加的維生素和礦物質所組成。脂肪組成通常係源於乳汁原料。總蛋白之目標可設定為符合人乳、牛乳之數值或較低之數值。總碳水化合物之目標通常設定為提供盡可能少之添加的糖(諸如蔗糖或果糖)來取得可接受的味道。通常,維生素A、鈣及維生素D之添加量為符合區域牛乳的營養貢獻。或者,於一些實施態樣中,維生素和礦物質之添加量可為每一份量提供約20%之膳食參考攝入量(DRI)或約20%之日需值(Daily Value)(DV)。再者,不同市場間之營養數值可根據所欲族群之經鑑定的營養需求、原料貢獻和地區規定而有所變化。
於某些實施態樣中,營養組成物為低過敏性。於其他實施態樣中,營養組成物為符合猶太教規的食
品(kosher)。再於其他之實施態樣中,營養組成物為非基改產品。於一實施態樣中,營養調和物不含蔗糖。營養組成物亦可不含乳糖。於其他實施態樣中,營養組成物不含任何中鏈三酸甘油酯油。於一些實施態樣中,組成物中不存有角叉菜膠。於其他實施態樣中,營養組成物不含所有樹膠(gum)。
所提供之實施例係用於說明本揭示內容之營養組成物的一些實施態樣,但不應該被解釋為對本揭示內容之營養組成物的任何限制。熟習本技藝之人士參照本說明書或實行本文所揭露之營養組成物或方法可清楚明白在本文之申請專利範圍內的其他實施態樣。本說明書,連同實施例係欲被視為僅用於示例,本揭示內容之範圍和精神係由接續在實施例後之申請專利範圍所指。
實施例1
本實施例說明根據本揭示內容之營養組成物的一實施態樣。
實施例2
本實施例說明根據本揭示內容之營養組成物的另一實施態樣。
本說明書中所引用之所有參考資料,包括,但不限於所有論文、出版物、專利案、專利申請案、演示、文本、報告、手稿、手冊、書籍、網路貼文、期刊文章、刊物,等之全部內容在此以引用方式納入本說明書中。本文中參考資料的論述只是為了概述由其作者所稱者,並非承認任何參考資料構成先前技藝。本申請人保留質疑所引用之參考資科的準確性和相關性之權利。
雖然本揭示內容之實施態樣已使用特定術語、裝置和方法描述,這類描述僅用於說明。所使用之文字是描述,而非限制之文字。可理解的是,本技藝之一般技術人士可在不背離本揭示內容之精神或範圍(其於後附
之申請專利範圍提出)的情況下作出改變和變化。此外,應理解的是,各種實施態樣之態樣可以全部或部分互換。例如,雖然已示例用於生產根據那些方法製造之市售無菌液體營養補充劑的方法,仍可以考慮其他用途。因此,所附之申請專利範圍的精神和範圍不應只限於其中所包含之版本的說明。
Claims (17)
- 一種用於增進小兒個體發育之方法,該方法包含投予小兒個體包括至少約0.08g/100kcal之十八碳四烯酸的營養組成物。
- 如申請專利範圍第1項之方法,其中該營養組成物中之十八碳四烯酸的存在量為約0.25g/100kcal至約3g/100kcal。
- 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括0.08g/100kcal至約1g/100kcal之γ-次亞麻油酸(gamma-linolenic acid)。
- 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括:a.至多約7g/100kcal之脂肪或脂質來源;b.至多約7g/100kcal之蛋白質或蛋白質等效來源(protein equivalent source);及c.至少約5g/100kcal之碳水化合物。
- 如申請專利範圍第4項之方法,其中該脂肪或脂質來源包含至少約0.5g/100kcal之富含十八碳四烯酸的植物油。
- 如申請專利範圍第4項之方法,其中該營養組成物進一步包括下列之一或多者:d.至少約10mg/100kcal之乳鐵蛋白(lectoferrin);e.約0.1g/100kcal至約1g/100kcal之益菌素(prebiotic)組成物,該益菌素組成物包含聚右旋糖(polydextrose)和半 乳寡醣(galacto-oligosaccharide);及f.至少約5mg/100kcal之另外的長鏈多不飽和脂肪酸。
- 如申請專利範圍第6項之方法,其中乳鐵蛋白之存在量為約10mg/100kcal至約200mg/100kcal。
- 如申請專利範圍第6項之方法,其中該另外的長鏈多不飽和脂肪酸的存在量更佳為約5mg/100kcal至約75mg/100kcal。
- 如申請專利範圍第6項之方法,其中聚右旋糖及半乳寡醣構成該益菌素組成物之至少約20%。
- 如申請專利範圍第1項之方法,其中該營養組成物為嬰兒配方或成長乳。
- 一種用於增進小兒個體發育之營養組成物,其包括:a.至多約7g/100kcal之脂肪或脂質來源,其中該脂肪或脂質來源包含至少約0.25g/100kcal之富含十八碳四烯酸的植物油;b.至多約7g/100kcal之蛋白質或蛋白質等效來源;及c.至少約5g/100kcal之碳水化合物;d.至少約10mg/100kcal之乳鐵蛋白;e.約0.1g/100kcal至約1g/100kcal之益菌素組成物,該益菌素組成物包含聚右旋糖和半乳寡醣;及f.至少約5mg/100kcal之另外的長鏈多不飽和脂肪 酸。
- 如申請專利範圍第11項之組成物,其中十八碳四烯酸之存在量為約0.25g/100kcal至約3g/100kcal。
- 如申請專利範圍第11項之組成物,其進一步包括0.08g/100kcal至約1g/100kcal之γ-次亞麻油酸。
- 如申請專利範圍第11項之組成物,其中乳鐵蛋白之存在量為約15mg/100kcal至約300mg/100kcal。
- 如申請專利範圍第11項之組成物,其中該另外的長鏈多不飽和脂肪酸的存在量更佳為約5mg/100kcal至約75mg/100kcal。
- 如申請專利範圍第11項之組成物,其中聚右旋糖及半乳寡醣構成該益菌素組成物之至少約20%。
- 如申請專利範圍第11項之組成物,其中該營養組成物為嬰兒配方或成長乳。
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US14/102,909 US20150157048A1 (en) | 2013-12-11 | 2013-12-11 | Nutritional compositions containing stearidonic acid and uses thereof |
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AR (1) | AR100028A1 (zh) |
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US20140107193A1 (en) * | 2011-10-14 | 2014-04-17 | Mead Johnson Nutrition Company | Nutritional composition containing a neurologic component of kaempferol and/or fisetin and uses thereof |
US20150290261A1 (en) * | 2014-04-10 | 2015-10-15 | Mead Johnson Nutrition Company | Methods of use for probiotics and prebiotics |
US20150305359A1 (en) * | 2014-04-24 | 2015-10-29 | Mead Johnson Nutrition Company | Nutritional compositions directed to subjects having cow's milk protein allergies |
JP7136807B2 (ja) | 2017-04-17 | 2022-09-13 | ザ・ユニバーシティ・オブ・シカゴ | ヒトの健康及び疾患の治療用途向けの短鎖脂肪酸の腸への送達用ポリマー材料 |
US11197917B2 (en) | 2017-12-01 | 2021-12-14 | ByHeart, Inc. | Formulations for nutritional support in subjects in need thereof |
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IE61701B1 (en) | 1986-07-17 | 1994-11-30 | Morinaga Milk Industry Co Ltd | Process for producing bovine lactoferrin in high purity |
US5407957A (en) | 1990-02-13 | 1995-04-18 | Martek Corporation | Production of docosahexaenoic acid by dinoflagellates |
US5013569A (en) * | 1990-05-21 | 1991-05-07 | Century Laboratories, Inc. | Infant formula |
DK165090D0 (da) | 1990-07-09 | 1990-07-09 | Kem En Tec As | Konglomererede partikler |
NZ241359A (en) | 1991-01-24 | 1994-08-26 | Martek Corp | Supplementation of infant formula by the addition of at least two different polyunsaturated fatty acids obtained from at least two different microbial sources; compositions comprising such oils |
US5374567A (en) | 1993-05-20 | 1994-12-20 | The United States Of America As Represented By The Secretary Of The Navy | Operational amplifier using bipolar junction transistors in silicon-on-sapphire |
US5405637A (en) * | 1993-06-30 | 1995-04-11 | Bristol-Myers Squibb Company | Milk protein partial hydrolysate and infant formula containing same |
EP1142484A2 (en) | 1994-02-16 | 2001-10-10 | Pharming Intellectual Property BV | Isolation of lactoferrin from milk |
SE9503926D0 (sv) | 1995-11-07 | 1995-11-07 | Pharmacia Biotech Ab | Adsorptionsförfarande och separationsmedium |
DE19757414A1 (de) * | 1997-12-23 | 1999-07-01 | Nutricia Nv | Fettmischung |
EP1087828B1 (en) | 1998-06-18 | 2008-09-17 | Upfront Chromatography A/S | Expanded bed adsorption system |
JP2001029010A (ja) * | 1999-07-26 | 2001-02-06 | Snow Brand Milk Prod Co Ltd | 栄養組成物 |
WO2001085329A2 (en) | 2000-05-12 | 2001-11-15 | Upfront Chromatography A/S | A bed adsorption system |
US6332533B1 (en) | 2000-08-29 | 2001-12-25 | H.H.H. Incorprorated | Media holder mouse pad |
WO2002096215A1 (en) | 2001-06-01 | 2002-12-05 | Upfront Chromatography A/S | Fractionation of protein containing mixtures |
DK1480524T3 (da) | 2002-03-07 | 2013-07-15 | Upfront Chromatography As | Fremgangsmåde til isolering af lactoferrin |
CN1674786A (zh) * | 2002-08-14 | 2005-09-28 | 纳幕尔杜邦公司 | 经涂布的含多不饱和脂肪酸的颗粒以及经涂布的含液体药物的颗粒 |
EP1634599A1 (en) * | 2004-08-20 | 2006-03-15 | N.V. Nutricia | Iimmune stimulatory infant nutrition |
EP1803358A1 (en) * | 2005-12-28 | 2007-07-04 | Laboratorios Ordesa, S.L | Infant immunological formula |
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WO2009099886A1 (en) * | 2008-01-31 | 2009-08-13 | Monsanto Technology Llc | Methods of improving dha deposition and related function and/or development |
JP2011519552A (ja) * | 2008-04-25 | 2011-07-14 | ビーエーエスエフ プラント サイエンス ゲーエムベーハー | 植物種子油 |
EP2251031A1 (en) * | 2009-05-12 | 2010-11-17 | Nestec S.A. | Lactoferrin and neuronal health and development in the infant gut |
US8968722B2 (en) * | 2010-12-29 | 2015-03-03 | Mead Johnson Nutrition Company | Milk-based nutritional compositions containing lactoferrin and uses thereof |
US20120269929A1 (en) * | 2011-04-22 | 2012-10-25 | Hugh Lippman | Fortified Milk-Based Nutritional Compositions |
US20130251829A1 (en) | 2012-03-23 | 2013-09-26 | Mead Johnson Nutrition Company | Probiotic derived non-viable material for infection prevention and treatment |
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- 2013-12-11 US US14/102,909 patent/US20150157048A1/en not_active Abandoned
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- 2014-11-17 WO PCT/US2014/065869 patent/WO2015088706A1/en active Application Filing
- 2014-11-20 TW TW103140264A patent/TW201608996A/zh unknown
- 2014-12-05 AR ARP140104563A patent/AR100028A1/es unknown
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WO2015088706A1 (en) | 2015-06-18 |
US20150157048A1 (en) | 2015-06-11 |
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