TW201244640A - Modulation of growth of bifidobacteria using a combination of oligosaccharides found in human milk - Google Patents
Modulation of growth of bifidobacteria using a combination of oligosaccharides found in human milk Download PDFInfo
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- TW201244640A TW201244640A TW101104099A TW101104099A TW201244640A TW 201244640 A TW201244640 A TW 201244640A TW 101104099 A TW101104099 A TW 101104099A TW 101104099 A TW101104099 A TW 101104099A TW 201244640 A TW201244640 A TW 201244640A
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- formulation
- sialyllactose
- weight
- fucosyllactose
- lactose
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- 241000186000 Bifidobacterium Species 0.000 title claims abstract description 7
- 229920001542 oligosaccharide Polymers 0.000 title description 14
- 150000002482 oligosaccharides Chemical class 0.000 title description 13
- 235000020256 human milk Nutrition 0.000 title description 12
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Classifications
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Landscapes
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Description
201244640 六、發明說明: 【發明所屬之技術領域】 本發明係關於含有供人類營養(例如嬰兒營養)之寡糖之 益菌助生質調配物,其調節雙叉乳桿菌之 生長。 【先前技術】 益菌助生質調配物提供寄生在宿主動物諸如哺乳動物 (例如人)的腸道中之有益細菌(諸如各類雙又乳桿菌)之養 分。此類菌群有助於從腸道中排除有害細菌,及亦能夠消 化宿主不能消化的一些化合物。因此,益菌助生質調配物 藉由幫助雙叉乳桿菌在宿主腸道中繁殖而有利於宿主。 根據 Wang 等人之 Am. J. Clin. Nutr.,74(4),510 (2001), 傳統嬰兒配方包含遠低於人奶之含量的與寡糖結合之唾液 酸。而且’按照Wang等人之j· pe(jiatr” 138,914-6 (2001), 饅食人奶之早產嬰兒之唾液包含含量兩倍於餵食市售嬰兒 配方之嬰兒的唾液酸。 EP 1255449敘述包含寡糖之營養調配物。按照Ep 125 5449 ’寡糖(尤其係果寡糖及唾液酸乳糖)能夠通過人類 小腸而不被消化及可藉由有限量微生物(包括雙叉乳桿菌 及乳桿菌(Z^ciokcz·///))而發酵。唾液酸乳糖(尤其係y·及 6 -唾液酸乳糖)天然地存在於人奶中,及被認為可抑制人 體中病源菌之結合。該專利敘述在營養調配物中之寡果糖 及3'-及/或6'-唾液酸乳糖之組合。 WO 2004/093557敘述一種包含唾液酸源(諸如唾液酸乳 161609.doc 201244640 糖)之嬰兒配方。 WO 2004/112509敘述一種爲了在新生嬰兒體内誘發形成 肠屏障之營養組合物,其中該組合物包括微生物及不可消 化的寡糖,其可為唾液酸寡糖。 WO 2007/11 4696敘述羊寡糖於刺激免疫系統之用途,諸 如3-或6-唾液酸乳糖。 WO 2009/059996敘述一種用於預防二次感染之包含3'-或6·-唾液酸乳糖之營養組合物》 美國專利號5,260,280敘述一種藉由投與人類患者有效量 之單離唾液酸乳糖而中和細菌腸毒素之方法。 【發明内容】 本發明提供一種包括21-岩藻糖基乳糖、3’-唾液酸乳糖及 6'-唾液酸乳糖之供人類口服之益菌助生質調配物。該調配 物調節在人類腸道中之雙又乳桿菌屬之生長。該調配物可 為嬰兒配方。 本發明亦提供一種用於調節或刺激雙又乳桿菌(例如雙 岐雙叉乳桿菌、短雙叉乳桿菌 {Bifidobacterium breve)反婪免雙 X%稈蛰[Bifidobacterium infantis))之竺長之方法。 【實施方式】 本發明提供一種包括相比單一寡糖可刺激更多雙叉乳桿 菌種類生長之寡糖組合之營養調配物。本發明之寡糖組合 有助於更廣範圍之有益腸道細菌繁殖,在服用該調配物之 人類個體之腸道中提供更多種類及更自然均衡的雙又乳桿 161609.doc 201244640 菌群。 本發明之調配物一般為可藉由例如飲用液體調配物經口 消化之食品或補充食品。在一實施例中,該調配物為嬰兒 可以常規方式飲用之嬰兒配方或奶替代品。 在本發明之一實施例中,調配物為包括至少約0J mg/ml 之2'·岩藻糖基乳糖、至少約0.1 mg/ml之6,-唾液酸乳糖及 至少約0.1 mg/ml之3,-唾液酸乳糖之液體。在本發明之一 實施例中,調配物為包括約〇.丨至1〇 mg/ml之2,-岩議糖基 乳糖、約0_1至10 mg/ml之6,-唾液酸乳糖及約(^至之❶ mg/ml之3’-唾液酸乳糖之液體。在另一實施例中,調配物 為包括約0_5至2 mg/ml之2’-岩藻糖基乳糖、約〇·5至2 mg/ml之6'-唾液酸乳糖及約1至4 mg/ml之3'-唾液酸乳糖之 液體。在另一實施例中,調配物為包括約1 mg/ml22,岩 藻糖基乳糖、約1 mg/ml之6,-唾液酸乳糖及約2 mg/ml之3,_ 唾液酸乳糖之液體。 在本發明之一個實施例中,調配物包括分別約〇 5至2 〇 比0.5至2·0ώ1.0至4.〇之重量比之2,·岩藻糖基乳糖、6,-唾 液酸乳糖及3'-唾液酸乳糖。在一個實施例中,3,_唾液酸乳 糖之重量含量至少與2,-岩藻糖基乳糖及/或6,_唾液酸乳糖 之含量一樣。在本發明之一個實施例中,調配物包括分別 約〇·9至U比0.9至U比U至2.2之重量t匕之2,_岩藻糖基乳 糖、6^唾液酸乳糖及3'-唾液酸乳糖。 在本發明之一個實施例中,調配物為乾粉。本發明之乾 粉調配物與本發明之液體調配物相同,除已經乾燥除去水 161609.doc 201244640 分之外。乾粉調配物可由添加水復原以形成本發明之液體 調配物。在本發明之一個實施例中,乾粉調配物包括乾於 調配物總重之至少約0.4重量%之2,_岩蕩糖基乳糖、至少: 0.4重量%之6,-唾液酸乳糖及至少約〇 8重量%之3、唾液酸 乳糖。在本發明之-個實施例中,乾粉調配物包括乾粉^ 配物總重之約0.4Μ·5重量%之2,_岩藻糖基乳糖 '約至 !.5重量%之6,·唾液酸乳糖及約〇8至3〇重量%之3,_唾液酸 乳糖。在本發明之-個實施例中,乾粉調配物包括乾粉^ 配物總重之約0.7至〇.9重量%之2••岩薄糖基乳糖、約〇刀至 0.9重量%之6,-唾〉夜酸乳糖及約14至17重量%之3,_唾液酸 乳糖。因此,此三種寡糖佔乾粉重量的^ 6至6〇%。此 段中之重量百分比係與本發明之任何液體調配物相同,但 该重量百分比係基於水之外的所有成分計算(下文稱 「乾重」)。 ~ 本發明之調配物亦可呈液體濃縮物形式,其包括與前述 液體調配物相同比例之相同成分,但含有較少的水及因此 較高濃度的其他成分。基於乾重之寡糖之百分比與本發明 之任何其他調配物相同。該液體濃縮物可與適量的水組合 以製備前述液體調配物。熟習此項技術者無需過度試驗可 輕易理解如何製備該液體濃縮物及如何確定與之組合的水 量。 ' 文令所用之術語「嬰兒配方」表示為嬰兒提供完全營養 及可在餘食嬰兒方面用做人奶替代品之營養調配物(呈液 體形式’或呈乾粉形式,其可經加水復原而形成液體嬰兒 161609.doc 201244640 配方)。該配方在此技術中眾所周知。 一般而言’呈即食液體形式之嬰兒配方提供6〇至7〇 Kcai/100 ml。嬰兒配方一般每100 Kcal包括:1.8至4.5 g 蛋白質,3.3至6.0§脂肪(脂質);3〇〇至〗2〇〇111§亞油酸;9 至14 g選自由乳糖、蔗糖、葡萄糖、葡萄糖漿、澱粉、麥 芽糊精及麥芽糖及其組合組成之群之碳水化合物;及必需 維生素及礦物質。乳糖可為嬰兒配方中的主要碳水化合 物。液體嬰兒配方可包含約67 Kcal/l 00 ml。嬰兒配方可 包含約1.8至3.3 g蛋白質/100 Kca丨,例如約i 8至丨」g蛋 白質/100 Kca卜 4r兒配方亦包括選自胞苷5'·單礴酸(CMP) '尿苷5'-單填 酸(UMP)、腺苷5’-單磷酸(AMP)、鳥苷5·-單磷酸(GMP)及 肌苷5·-單磷酸(IMP)及其混合物。嬰兒配方亦可包括葉黃 素、玉米黃質、果寡糖、半乳寡糖、唾液酸乳糖及/或岩 藻糖基乳糖。長鏈多不飽和脂肪酸(諸如二十二碳六烯酸 (DHA)及花生四烯酸(AA))可併入嬰兒配方中。嬰兒配方中 亦可包括胺基酸《嬰兒配方亦可包括相關技術中已知的其 他成分。 嬰兒配方的目的在於為嬰兒提供嬰兒需要的所有能量及 營養,及嬰兒可以其他方式從其母乳中接收。然而,人奶 為極其複雜的組合物及嬰兒配方不能精確地模擬該組合 物。多年來,熟習此項技術者致力於製備更像人奶的嬰兒 配方,及製備可提供嬰兒儘可能與人奶一樣多益處的嬰兒 配方。 161609.doc 201244640 :般慣例為從牛奶製備嬰兒配方,因為 數或全部營養存在於牛奶中。然而,牛 =之大夕 不同的細士 ,, 干奶具有與人奶顯著 H如’牛奶包括具有約20:80之乳清/路蛋白 蛋白質内容物,而人奶具有約6G術比。牛奶亦且 ^於人奶之α·乳清蛋白(乳清蛋白),且多數牛路蛋白 内谷物為β_乳球蛋白,其在 笪》甘凡 里不顯者。因為此 等其他區別,熟習此項技術者已經開發出改質牛奶的方 法,例如藉由製備可用於嬰兒配方中之富含α_乳清蛋白之 牛乳清組分,從而提供具有更像人奶之蛋白譜之配方。此 類方法在相關技術中為人所熟知^例如,美國專利案號 ,’778敘述種藉由組合富含α·乳清蛋白之乳清組分及 少量牛奶組分而製備之嬰兒配方。該專利亦敘述一種具有 減少蛋白質含量之嬰兒配方。牛奶包含約15至16 g/L蛋 白質’而人奶包含約丨i g/L。 除嬰兒配方外之其他營養調配物亦在相關技術中為人所 沾知。例如,存在為兒童或成人設計的調配物,其欲用於 提供充分營養或補充兒童或成人消費者之飲食。熟習此項 技術者已努力製備對消費者儘可能有益的此類調配物。 券糖2'-岩藻糖基乳糖、6'-唾液酸乳糖及3,_唾液酸乳糖 為可購得之已熟知化合物。 已經發現2’-岩藻糖基乳糖刺激雙岐雙叉乳桿菌及嬰兒雙 又乳桿菌之生長’但會抑制短雙又乳桿菌之生長,而6,_唾 液酸乳糖刺激嬰兒雙叉乳桿菌之生長,及3,_唾液酸乳糖刺 激短雙叉乳桿菌及嬰兒雙叉乳桿菌之生長。已經發現,利 161609.doc 201244640 二種寡糖組合可有利地影 中之生長。因此,本發明 響 促 用文中所述之含量及比例之此 此三種雙又乳桿菌在人體腸道 進細菌在消費者腸中健康的平衡 無論呈液體、液體濃縮物或乾粉形式,本發明之調配物 可利用習知方法組合該調配物之成分(該等成分在此技術 中為眾所周知)而製備。熟習此項技術者無需過度試驗可 輕易理解如何製備該調配物或能確定如何製備該調配物。 在本發明之方法中’本發明之液體營養調配物經口投與 人類消費者以調節雙叉乳桿菌(例如雙岐雙叉乳桿菌、短 雙又乳桿菌及嬰兒雙叉乳桿菌)之生長。 列出以下實例以說明本發明之某些實施例,但不應視為 限制本發明之範圍。 實例1 : 2’-岩藻糖基乳糖、3,_唾液酸乳糖及6,_唾液酸乳糖 對嬰兒雙又乳桿_ ATCC 1569*7、短雙又乳桿菌ATCC 157〇0及雙岐雙又乳桿菌ATCC 29521生長之影響。 使用加强型梭菌培養基(RCM)培養雙又乳桿菌。不含葡 萄糖之RCM用作對照培養基。RCM為用於培養及計數厭氧 菌之熟知培養基’其首先由Hirsch及Grinstead在J. Dairy Res·,21:101 (1954)中調配。 測試成分為以下列濃度溶於對照培養基中之2'-岩藻糖基 乳糖、6'_唾液酸乳糖及3'-唾液酸乳糖:1 mg/ml 2'-岩藻糖 基乳糖’ 1 mg/ml 6'-唾液酸乳糖,及2 mg/ml 3,-唾液酸乳 糖0 雙叉乳桿菌分別在RCM中厭氧生長整夜,隨後測量及稀 I61609.doc 201244640 釋成〇· 1之光密度’如經吸收光譜法在595 nm測量,及隨 後進步稀釋1 〇倍以製備工作原料。對於每一測試,將5 〇 μ1工作原料添加至含有200 μΐ對照培養基(48孔)或200 μΐ測 試成分溶液(48孔)之96孔板之各孔中。該板厭氧生長3〇小 時’每隔15分鐘在abs 595 nm讀取光密度。將相似孔之數 值平均及對時間繪圖(圖i ' 3,及5至7),及計算在3〇小時 期間曲線下面積(AUC)(圖2及4)。 A· 2’-岩藻糖基乳糖及雙岐雙叉乳桿菌 對兩次實驗的數值取平均值。如圖1及2所示,在細菌按 照上述步驟生長8小時後’在含有測試成分之孔中,生長 顯著更快,及測試成分的AUC約高出25.1%。 B· 2’-岩藻糖基乳糖及嬰兒雙叉乳桿菌 如圖3及4所示,在細菌按照上述步驟生長8小時後,在 含有測試成分之孔中’生長顯著更快,及測試成分的AuC 約高出30.5°/〇。 C. 6’-唾液酸乳糖及嬰兒雙又乳桿菌 如圖5所示’在細菌按照上述步驟生長12小時後,在含 有測試成分之孔中,生長顯著更快。 D. 3’-唾液酸乳糖及短雙又乳桿菌 如圖6所示,在細菌按照上述步驟生長6小時後,在含有 測試成分之孔中,生長顯著更快。 E. 3’-唾液酸乳糖及嬰兒雙叉乳桿菌 如圖7所示’在細菌按照上述步驟生長7小時後,在含有 測試成分之孔中,生長顯著更快。 161609.doc -10· 201244640 實例2 : 如下敘述適合餵食嬰兒之本發明之液體益菌助生質配 方: 成分 Wt/100 ml 成分 Wt./100 ml 蛋白質 1.4 g 菸酸 0.75 mg 碳水化合物 7g 葉酸 16 pg 脂肪 3.5 g 生物素 3 μ% 2’-岩藻糖基乳糖 0.10 g 泛酸 0.5 mg 6L唾液酸乳糖 〇.l〇g 鈣 63 mg T-唾液酸乳糖 0.20 g 磷 36 mg 維生素A 1 mg 鎂 6.7 mg 維生素C 13 mg 鐵 1 mg 維生素D 1-6 Mg 鋅 0.9 mg 維生素E 1 mg 錳 7-5 Mg 維生素K 10 pg 銅 50 pg 維生素B1 0.15 mg 碘 15 pg 維生素B2 0.16 mg 納 24 mg 維生素B6 80 pg 鉀 97 mg 維生素B12 0.2 pg 氯化物 65 mg CMP 1.9 mg 硒 2gg UMP 0.75 mg 膽驗 15 mg AMP 0.6 mg 肌醇 6,7 mg GMP 0.3 mg 牛磺酸 7 mg IMP 0.3 mg 葉黃素 DHA 11 mg 水 補足 花生四晞酸 18 mg 在該示例性調配物中使用之蛋白質來自牛奶及乳清,其 中60至65%為乳清蛋白及35至40°/。為酪蛋白。在該調配物 中,具有增加α-乳清蛋白含量之乳清組分已經用於提供約 0.2 g α-乳清蛋白/100 ml調配物之蛋白質含量。 實例3 : 如下敘述適合餵食嬰兒之本發明之液體益菌助生質配 方: 16l609.doc • 11 - 201244640 成分 蛋白質 碳水化合物 脂肪 岩藻糖基乳糖 6'-唾液酸乳糖 31-唾液酸乳糖 維生素A 維生素C 維生素D 維生素E 維生素K 維生素B1 維生素B2 維生素B6 維生素B12 DHA 花生四烯酸 膽驗 肌醇 牛確酸 m/100 ml
g g g18g g gggll2mmp ·3·3·61λ·2902 l7-3-aoc!olL 1 mg 10 pg 0.15 mg 0.16 mg 80 pg 0.2 pg 12 mg 18 mg 15 mg 6.7 mg 7 mg 成分 Wt./100 ml 於酸 0.75 mg 葉酸 16 Mg 生物素 3 μξ 泛酸 0.5 mg 63 mg 填 36 mg 鎂 6.7 mg 鐵 1 mg 鋅 0.9 mg 猛 7·5 pg 銅 50 pg 15 pg 納 24 mg 钟 97 mg 氯化物 65 mg 石西 2 μ% 葉黃素 12 pg 水 補足 在該示例性調配物中使用之蛋白質來自牛奶及乳清,其 中60至65%為乳清蛋白及35至40%為酪蛋白。在該調配物 中,具有增加α-乳清蛋白含量之乳清組分已經用於提供約 0.2 g α-乳清蛋白/100 ml調配物之蛋白質含量。 熟習此項技術者可以作出文中未說明之本發明之諸多變 動。本發明不限於文中說明及敘述之實施例,但涵蓋在隨 附申請專利範圍内之所有標的物。 【圖式簡單說明】 圖1顯示雙岐雙又乳桿菌在對照培養基及包含2'-岩藻糖 基乳糖之培養基中之生長曲線。 圖2顯示圖1中曲線之AUC。 161609.doc •12- s 201244640 圓3顯示嬰兒雙又乳桿菌在對照培養基及包含2·_岩藻糖 基乳糖之培養基中之生長曲線。 圖4顯示圖3中曲線之AUC。 圖5顯不嬰兒雙又乳桿菌在對照培養基及包含6,_唾液酸 乳糖之培養基中之生長曲線。 圖6顯不短雙叉乳桿菌在對照培養基及包含3,-唾液酸乳 糖之培養基中之生長曲線。 圖7顯示嬰兒雙叉乳桿菌在對照培養基及包含3,_唾液酸 乳糖之培養基中之生長曲線。 161609.doc
Claims (1)
- 201244640 七、申請專利範圍: U 一種包括2·-岩藻糖基乳糖、3,-唾液酸(sialyl)乳糖及6ι_唾 液酸乳糖之供人類口服之益菌助生質(prebiotic)調配 物’其中3,·唾液酸乳糖之重量含量至少與2'-岩藻糖基乳 糖之含量一樣。 2. 如請求項1之調配物,其中21-岩藻糖基乳糖、3,-唾液酸 乳糖及6’-唾液酸乳糖佔調配物乾重的約1.6至6.0%。 3. 如請求項1或請求項2之調配物,其中該調配物包括分別 約0.5至2.0比〇.5至2.0比1.0至4.0之重量比之2’-岩藻糖基 乳糖、6,-唾液酸乳糖及3·-唾液酸乳糖。 4. 如請求項3之調配物,其中該重量比分別爲約〇.9至1.1比 0.9至 Μ 比 18至 2.2。 5. 如請求項1之調配物,其中該調配物包括嬰兒配方。 6. 如請求項5之調配物,其中該嬰兒配方為包括約〇. 1至i 〇 mg/ml之2’-岩蕩糖基乳糖、約o.i至1〇 mg/ml之6'-唾液酸 乳糖及約〇. 1至20 mg/ml之3'-唾液酸乳糖之液體。 7_如請求項5之調配物’其中該嬰兒配方為包括約0.5至2 mg/ml之2’-岩蕩糖基乳糖、約〇.5至2 mg/ml之6’-唾液酸 乳糖及約1至4 mg/ml之3’-唾液酸乳糖之液體。 8,如請求項5之調配物’其中該嬰兒配方為包括約1 mg/ml 之2'-岩藻糖基乳糖、約1 mg/ml之6'-唾液酸乳糖及約2 mg/ml之3'-唾液酸乳糖之液體。 9_如請求項5之調配物,其中該嬰兒配方為包括約0.4至ι.5 重量°/。之2'-岩藻糖基乳糖、約0.4至1.5重量%之6'-唾液酸 161609.doc 201244640 乳糖及約0.8至3.0重量%之3,-唾液酸乳糖之乾粉。 1〇·如請求項9之調配物,其包括約〇.7至0.9重量%之2,_岩藻 糖基乳糖、約0.7至〇.9重量%之6’-唾液酸乳糖及約I·4至 1.7重量。/〇之3'-唾液酸乳糖。 11. 一種如請求項1至10中任一項之調配物之用途,其用於 製備用於調節或刺激在人體腸道中之雙又乳桿菌 (Bifidobacteria)釔長的藥物 〇 S 161609.doc
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AU2012215042B2 (en) | 2011-02-10 | 2016-01-14 | Société des Produits Nestlé S.A. | Modulation of growth of bifidobacteria using a combination of oligosaccharides found in human milk |
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EP3368047B1 (en) * | 2015-10-28 | 2023-04-26 | Glycom A/S | Synthetic composition and method for modulating emotion and mood disorders |
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US20140371173A1 (en) | 2014-12-18 |
CN104126749A (zh) | 2014-11-05 |
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IL227487A (en) | 2015-10-29 |
ES2527200T3 (es) | 2015-01-21 |
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WO2012107865A3 (en) | 2012-11-01 |
US20120208782A1 (en) | 2012-08-16 |
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CA2825697A1 (en) | 2012-08-16 |
ZA201306751B (en) | 2015-05-27 |
US20150141367A1 (en) | 2015-05-21 |
RU2013141449A (ru) | 2015-03-20 |
BR112013020108A2 (pt) | 2017-06-13 |
PT2672844E (pt) | 2015-02-04 |
MY161034A (en) | 2017-04-14 |
IL227487A0 (en) | 2013-09-30 |
EP2792252A2 (en) | 2014-10-22 |
EP2672844B2 (en) | 2022-10-05 |
PL2672844T3 (pl) | 2015-04-30 |
RU2586928C2 (ru) | 2016-06-10 |
EP2792252B1 (en) | 2018-09-12 |
SG192095A1 (en) | 2013-08-30 |
CN103347405A (zh) | 2013-10-09 |
ES2527200T5 (es) | 2022-12-29 |
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MX362129B (es) | 2019-01-07 |
AU2012215042B2 (en) | 2016-01-14 |
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