TW201233342A - Methods for decreasing the incidence of necrotizing enterocolitis, colic, and short bowel syndrome in an infant, toddler, or child - Google Patents

Methods for decreasing the incidence of necrotizing enterocolitis, colic, and short bowel syndrome in an infant, toddler, or child Download PDF

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TW201233342A
TW201233342A TW100149621A TW100149621A TW201233342A TW 201233342 A TW201233342 A TW 201233342A TW 100149621 A TW100149621 A TW 100149621A TW 100149621 A TW100149621 A TW 100149621A TW 201233342 A TW201233342 A TW 201233342A
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Taiwan
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fatty acid
fat
weight
oil
nutritional
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TW100149621A
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Chinese (zh)
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Chron-Si Lai
Keith A Garleb
John B Lasekan
Steven R Davis
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Abbott Lab
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Priority claimed from US13/333,936 external-priority patent/US8877812B2/en
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Publication of TW201233342A publication Critical patent/TW201233342A/en

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Abstract

Disclosed are nutritional formulations including predigested fats that can be administered to preterm infants, infants, toddlers, and children for improving tolerance, digestion, and absorption of nutrients and for reducing the incidence of necrotizing enterocolitis, colic, and short bowel syndrome. The predigested fats include fatty acid-containing monoglycerides and/or a fatty acid component.

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201233342 六、發明說明: 【發明所屬之技術領域】 ★本發明係關於包含預消化脂肪之營養品且係關於使用該 等營養品之方法。更特定而言,本發明係關於包含含有脂 肪酸之單酸甘油酯及/或脂肪酸組分的嬰兒、幼兒及小兒 產品,其提供營養益處,包括改善消化、耐受性及營養素 吸收以及降低壞死性小腸結腸炎、腹痛及短腸症之發生 率。 相關申請案之交又參考 本申請案主張2010年12月2,9曰申請之美國臨時申請案第 61/428,168號、2010年12月29日申請之美國臨時申請案第 61/428,173號、2010年12月29日申請之美國臨時申請案第 6 1/428,176號、20 10年12月29日申請之美國臨時申請案第 61/428,177號及2010年12月29曰申請之美國臨時申請案第 61/428,185號的權益’其揭示内容以全文引用之方式併入 本文中。 【先前技術】 包含有目標地選擇之營養素的營養液體及粉末(包括嬰 兒及小兒配方)為吾人所熟知且能廣泛獲得,其中一此可 提供單一之營養來源,而其他可提供補充來源。該等營養 物包括可用水或其他含水液體復原之粉末,以及濃縮型及 即飲型營養液體,諸如基於牛奶或蛋白之乳液。該等營養 液體在與選定營養成分一起調配時尤為適用。 儘管通常認為母乳為新生嬰兒之最佳營養,但並非每位 161219.doc 201233342 母親能成功地以母乳哺育。母乳替代品(嬰兒配方)可提供 完整營養,且已證明其能滿足嬰兒正常生長及發育營養需 求。不幸的是,小比例之嬰兒配方餵養新生兒可能會遇到 胃腸道(GI)不耐性問題,包括軟便、脹氣、壞死性小腸結 腸炎、腹痛及其類似問題。 GI不耐性問題可至少部分歸因於嬰兒營養素消化及吸收 不完全。為解決該耐受性問題,一些嬰兒配方排除乳糖作 為成分’而其他以水解蛋白替代完整乳蛋白以減輕嬰兒消 化系統的負擔。 此外’ 一些配方餵養新生嬰兒之脂肪吸收速率比母乳餵 養嬰兒低得多。此脂肪吸收速率之差異隨嬰兒逐漸成熟而 減小。據推測,新生嬰兒缺乏脂肪酶,且因此其無法與接 受母乳中之脂肪酶的母乳餵養嬰兒同等好地消化及吸收脂 肪。 早產兒之消化系統發育不及足月嬰兒之消化系統,其益 發比足月嬰兒需要更多營養素(熱量)來促進生長及發育。 中鏈三酸甘油酯(MCT油)易於消化及吸收,且已包含於早 產兒配方中以改善配方脂肪、蛋白及鈣吸收。然而,中鏈 三酸甘油酯中包含之中鏈脂肪酸不被用於再合成三酸甘油 酯以在MCT油經消化及吸收之後形成乳糜微粒。因為咸信 許多脂溶性營養素(諸如類胡蘿蔔素及維生素A、D ' E及 K)在進入全身性循環之前經封裝至乳糜微粒中,因此MCT 油對脂溶性營養素吸收提供之益處(其對於生長及發育亦 重要)可能受到更多限制。 161219.doc 201233342 儘管過去已嘗試解決⑽題及上文提及之其他問題,但 理想的是提供可提供與母乳類似之營養益處且亦提供非水 溶性疏水性營養素之良料受性、消化及吸收以及使諸如 壞死性小腸結腸炎、腹痛及短腸症之病況發生率降低之嬰 兒及小兒配方。此外’若該等配方無穩定劑且特定而言無 角叉菜膠’則將為有益的。 【發明内容】 本發明係關於營養品,且特定而言係關於嬰兒配方,其 包含預消化脂肪’該預消化脂肪包含含有脂肪酸之單酸甘 油醋及/或脂肪酸組分。該等營養組合物可有利地用於改 善營養素(包含非水溶性/脂溶性營養素)耐受性、消化及吸 收,以及用於降低壞死性小腸結腸炎、腹歧短腸症之發 生率。在某些實施例中,脂肪酸組分可為脂肪酸形式,或 以脂肪酸之弼鹽或鎖鹽形式提#,由Λ提供其他營養素之 其他益處。 -種實施例為-種降低嬰兒、幼兒或孩童之壞死性小腸 結腸炎發生率之m方法包括識別易於患上壞死性小 腸結腸炎之嬰兒、幼兒或孩童且向該嬰兒、幼兒或孩童投 與包含至少10 Wt%之至少一種游離脂肪酸組分、含有脂肪 酸之單酸甘油酯或其組合之營養品。 另一實施例為一種降低嬰兒、幼兒或孩童腹痛發生率之 方法。該方法包括識別易於患上腹痛之嬰兒、幼兒或孩童 且向該嬰兒、幼兒或孩童投與包含至少1〇 wt%之至少一種 游離知肪酸組分、含有脂肪酸之單酸甘油酯或其組合之營 1612l9.doc 201233342 養品。 另一實施例為一種降低嬰兒、幼兒或孩童短腸症發生率 之方法。該方法包括識別易於患上短腸症之嬰兒、幼兒或 孩童且向該嬰兒、幼兒或孩童投與包含至少10 Wt%之至少 一種游離脂肪酸組分'含有脂肪酸之單酸甘油酯或其組合 之營養品》 已發現,包含預消化脂肪(諸如如本文所述之單酸甘油 酯及脂肪酸)之營養品(諸如嬰兒、幼兒及小兒配方)可減輕 嬰兒脂肪消化系統之總體負擔以改善嬰兒脂肪消化及吸 收,包含非水溶性/脂溶性營養素吸收。特定而言,小腸 近端部分中對預消化脂肪之吸收刺激CCK分泌,此促使胰 腺α細胞成熟及消化酶分泌。又,GLP-1及GLP-2分泌受到 刺激’此進一步促使腸道成熟。 令人驚訝地,使用預消化脂肪以及後續分泌CCK及GLP-1 使得GI轉運延遲且刺激胰腺酶分泌以使得營養素消化及吸 收更為完全。進入嬰兒結腸之營養素量的減少導致結腸醱 酵減少,此為脹氣及軟便問題之部分原因。另外,已發現 使用預消化脂肪可降低壞死性小腸結腸炎、腹痛及/或短 腸症之發生率。 此外,已發現預消化脂肪之不飽和脂肪酸組分可與鈣或 鎂源反應且所得形成之鹽令人驚訝地為生物可用。除提供 良好鈣或鎂源以外,該等鈣或鎂鹽亦令人驚訝的是’與通 常有苦味且賦予強烈咽喉灼熱感受之脂肪酸相比較為溫 和。此外,已發現脂肪酸鈣鹽或鎂鹽令人驚訝地起到使營 161219.doc 201233342 養乳液穩定之作用’此係因為其不會形成在乳液中難以分 散之沈降物’不同於有此傾向之許多不溶性鈣鹽。因此, 在多個實施例中,包含脂肪酸鈣鹽或鎂鹽作為預消化脂肪 之部分可減少對穩定劑(諸如角又菜膠)之需求。 【實施方式】 本文所述之營養品包括預消化脂肪。在多個實施例中, 該等產品包含含有脂肪酸之單酸甘油酯及脂肪酸組分以使 得預消化脂肪系統包含兩種組分。藉由減輕嬰兒、幼兒或 孩童消化系統之負擔,在提供穩定的生物可用產品之同時 實現多種益處。營養品之該等及其他特徵以及多種視情況 存在之變化及加料中之某些在下文中詳細描述。 術語「殺菌爸封裝」及「殺菌爸殺菌」在本文中可互換 使用’且除非另外說明,否則係指以營養液體填充容器 (最舨為金屬罐或其他類似封裝)且隨後使經液體填充之 封裝經受必要之熱殺菌步驟以形成經殺菌之殺菌釜封裝營 養液體產品的常見操作。 除非另外制,否則如本文利之術語「無菌封裝」係 才曰不依賴於上述殺菌釜封裝步驟製造封裝產品,其中營養 液體及封裝在填充之前分開經過殺菌,且隨後在經殺菌或 無菌加工條件下組合以形成經殺菌、無菌封裝之營養液體 產品。 「除非另外說明,$則如本文所用之術語「脂肪」及 可互換使用,係指源自植物或動物或由其加工而得 之知質物質。該等術語亦包含合成脂質物質,只要該等合 161219.doc 201233342 成物質適合人類口服即可。 除非另外說明,否則如本文所用之術語「存放穩定」係 指在封裝且隨後在18_24t:下儲存至少3個月(包含約6個月 至約24個月’且亦包含約12個月至約18個月)之後仍在商 業上具穩定性之營養品。 如本文所用之術語「營養調配物」或「營養品」或「營 養組合物」可互換使用,且除非另外說明,否則係指液體 及固體(包含半液體及半固體)人乳強化劑、液體及固體早 產兒配方、液體及固體嬰兒配方、液體及固體第二階段配 方、液艘及固體小兒配方以及液體及固體幼兒配方。該等 固體可為可經復原以形成營養液體之粉末,所有該等固體 均包括脂肪、蛋白及碳水化合物中之一或多者且適於人類 經口服用。 除非另外說明,否則如本文所用之術語「營養液體」係 指呈即飲魏體形式、濃縮形式之營養品及藉由在使用之 前使本文所狀㈣粉末復原而製狀營養液體。 除非另外說明,否則如本文所用之術語「營養粉末」係 指在服用之前可用水或另—含水液體復原之呈可流動或可 自取形式的營養品’且包含噴霧乾燥及乾混合/乾摻合粉 除非另外說明,否則如太令從„ Γ 個 在 只J如冬文所用之術語「嬰兒」係指 月大或更幼小之人。如太令私 本文所用之術語「早產兒」係 懷孕36週之前出生之嬰兒。 除非另外說明,否則如太古&amp; J如本文所用之術語「幼兒」係指 1612l9.doc 201233342 歲以上至三歲之人。 除非另外說明,否則如本文所用之術語「孩童」係指三 歲以上至十二歲之人。 除非另外說明,否則如本文利之術語「預消化脂肪」 . 係指含有脂肪酸之單酸甘油酯及/或脂肪酸組分。 - 除非另外說明,否則如本文所用之術語「嬰兒配方」係 指適於嬰兒服用作為主要營養源之液體及固體營養品。 除非另外說明,否則如本文所用之術語「早產兒配方」 係私適於早產兒服用作為主要營養源之液體及固體營養 σσ 0 除非另外說明,否則如本文所用之術語「人乳強化劑」 係私適合與母乳或早產兒配方或嬰兒配方混合以供早產或 足月嬰兒服用之液體及固體營養品。 除非另外說明,否則如本文所用之術語「含有脂肪酸之 單酸甘油酯」係指由一個經由酯鍵在甘油分子之Sn—Wa)、 8η·2(β)或Sn_3(a,)位置之一者處共價鍵結至甘油分子的脂 肪酸鍵組成之甘油酯。 除非另外說明,否則如本文所用之術語「脂肪酸組分」 係指源自其中肉豆蔻酸、棕櫚酸及硬脂酸總量小於2〇%(以 重量計)之來源的游離脂肪酸或脂肪酸鹽(諸如脂肪 或鎂鹽)。 Λ 除非另外說明,否則如本文所用之術語「脂溶性營養 素」係指非水溶性營養素,諸如油可溶性(脂溶性)維生素 (例如維生素A、D、£及1(:)、類胡蘿蔔素(例如葉黃素、 161219.doc 201233342 β月蘿_素、番知紅素等)、酿脂(神經結酶脂)、固醇及植 物化學品。 無’疋否明確揭示’如本文所用之數值範圍均意欲包含 彼圍内之每·~數值及數值子集。此外,該等數值範圍應 視為對針對該範圍内任何數值或數值子集之主張提供支 持。舉例而言,揭示1至10應理解為支持2至8、3至7、5至 6' 1至9、3.6至4.0、3.5至9·9等之範圍。 除非另外說明或在有提及之語境下明確相反暗示,否則 本發月中所有提及之單數特徵或限制均應包含對應之複數 特徵或限制,且反之亦然。 除非另外說明或在有提及組合之語境下明確相反暗示, 否則如本文所用之所有方法或製程步驟組合均可以任何次 序進行。 本發明營養品之各個實施例亦可實質上無本文所述之伯 何視情況存在或選定的成分或特冑’其限制|件為其餘! 養品應仍含有如本文所述之所有所需成分或特徵。在此負 景下’且除非另外說明’否則術語「實質上無」意謂選茨 營養品含有小於功能量之視情況存在之成分,—般小於 重量/〇(包含小於〇_5重量% ’包含小於〇」重量%且亦包含丨 重量%)之該視情況存在或選定的成分。 營養品及方法可包括如本文所述之產品要素以及本文戶片 述或另外適用於營養品及方法應用中之任何其他或視= 存在之要素,由其組成或基本上由其組成。 產品形式 161219.doc -10- 201233342 本發明之含有預消化脂肪的營養品及相關方法可以任何 已知或另外適合之口服產品形式來調配及執行。任何固 體、半固體、液體、半液體或粉末形式(包括其組合或變 化形式)在本文中均適用’其限制條件為該等形式允許安 • 全且有效地向個體經口傳遞亦如本文所定義之各成分。 本發明之營養品包含如本文所述之預消化脂肪。該等產 °»可視情況包含含有脂肪酸之單酸甘油酯或脂肪酸組分與 下文所述之其他脂肪來源的組合。 。亥等產品可声含包括本文所述之成分且口服安全又有效 之任何產品形式。該等營養品可經調配以僅包含本文所述 之成分,或可用視情況存在之成分改質以形成多種不同之 產品形式。 本發明之營養品較佳經調配為飲食產品形式其在本文 中定義為以因而含有脂肪、蛋白及碳水化合物中之至少一 者且較佳亦含有維生素、礦物質或其組合之產品形式包括 本發明之成分的彼等實施例。在多個實施例中,該產品將 包括預消化脂肪與蛋白質、碳水化合物、維生素及礦物質 之組合以產生營養品。 一該等營養品可用足夠種類及量之營養素調配以提供單 主要或補充性之營養來源,或提供專用於羅患特定疾 病或病況之個體或具有目標營養益處的營養品。 舉例而言’適合與如本文揭示之預消化脂肪一起使用之 產品形式的特定非限制性實例包含液體及粉末狀人乳強化 劑、液體及粉末狀早產兒配方、液體及粉末狀嬰兒配方、 I6l2l9.doc •11 · 201233342 液體及粉末狀要素及半要素配方、液體及粉末狀小兒配方 以及液體及粉末狀幼兒配方。 營養液體 營養液體包含濃縮型及即食型營養液體。該等營養液體 最一般地經調配為懸浮液或乳液。 適用之營養乳液可為包含蛋白質、脂肪及碳水化合物之 含水乳液。該等乳液在約至約25 °c下通常為可流動或 可飲用之液體且一般呈水包油、油包水或複合含水乳液形 式’不過該等乳液最一般為具有連續水相及不連續油相之 水包油乳液形式。 營養乳液可為存放穩定的且一般為存放穩定的。該等營 養乳液以營養乳液之重量計一般含有高達約95重量。/〇之 水’包括約50重量%至約95重量❹/❶,亦包括約60重量%至 約90重量% ’且亦包括約7〇重量%至約88重量%之水。營 養乳液可具有各種產品密度,但最一般具有大於.約丨〇3 g/ml之密度’包括大於約1.04 g/mi,包括大於約1.055 g/ml ’包括約1.06 g/ml至約1.12 g/ml,且亦包括約1.085 g/ml至約 1.10 g/ml。 營養乳液可具有為符合最終使用者之營養需求而定製之 熱量密度’不過在大多數情況下該等乳液通常包含至少19 kcal/fl oz(660千卡/公升)、更一般為約2〇 kcal/fl oz(675-680 千卡/公升)至約25 kcal/fl 〇z(820千卡/公升)、甚至更一般 為約 20 kcal/fl 〇z(675-680 千卡 /公升)至約 24 kcal/fl oz (800-810千卡/公升)。通常而言,22-24 kcai/n 〇z(74〇_81〇 161219.doc -12- 201233342 千卡/公升)配方更普遍用於早產或低出生體重的嬰兒,且 20-21 kCal/fl OZ(675-680至7〇〇千卡/公升)配方更常用於足 月嬰兒。在某些實施例中,乳液可具有約1〇〇千卡/公升至 約660千卡/公升之熱量密度,包括約15〇千卡/公升至約5〇〇 千卡/公升。 營養乳液可具有約3.5至約8範圍内之1)11值,但最有利地 為約4.5至約7.5範圍内’包括約55至約7 3,包括約㈠至 約 7.2。 儘管營養乳液之服用量可視多種變數而變化,但典型之 服用量通常為至少約2 mL,或甚至至少約5 mL,或甚至至 少約10mL,或甚至至少約25〇1卜包括約2mL至約3⑼出匕 範圍内,包括約4 mL至約250 mL,且包括約1〇 mL至約 240 mL。 如上所述,營養品亦可為半液體形式,包括特性(諸如 流動特性)介於中間態(在液體與固體之間)之彼等形式。例 不性半液體包括黏稠奶昔及液體凝膠。 營養固體 營養固體可為任何固體形式,但—般為可流動或實質上 可流動的微粒組合物形式,或至少為微粒組合物。尤其適 。之營養固體產品形式包括經喷霧乾燥、聚、结或乾摻合之 粉末組合物。該等組合物可容易地肖類似其他裝置 來咨取或量測’其中該等組合物可容易地由預期使用者以 適合之含水液體(一般為水)來復原以形成營養調配物以供 即刻經口或經腸使用。在此背景下,「即刻」使用通常意 I61219.doc 201233342 謂較佳正好在復原後約48小時之内,最一般在約24小時之 内。 營養粉末可在使用之前用水復原至為符合最終使用者之 營養需求而定製之熱量密度’不過在大多數情況下該等粉 末用水復原而形成包含至少19 kcal/fl oz(660千卡/公升)' 更一般為約 20 kcal/fl 〇z(675-680千卡/公升)至約25 kcal/fl oz(820千卡/公升)' 甚至更一般為約20 kcal/fl OZ(675-680 千卡/公升)至約24 kcal/fl 〇z(800-810千卡/公升)之組合 物。通常而言,22-24 kcal/fl oz(740-8 10千卡/公升)配方更 普遍用於早產或低出生體重的嬰兒,且2〇_21 kcal/fl oz(675-680至700千卡/公升)配方更常用於足月嬰兒。在某 些實施例中,復原粉末可具有約5〇千卡/公升至約66〇千卡/ 公升之熱量密度,包括約! 〇〇千卡/公升至約5〇〇千卡/公 升。 如上所述,營養品亦可為半固體形式,包括特性(諸如 剛性)介於中間態(在固體與液體之間)之彼等形式。一些半 固體實例包括布丁、明膠及膏團。 預消化脂肪系統 A·含有脂肪酸之單睃甘油輯 在某些實施例中’本發明之營養品包含單獨或與如1 所述之脂肪酸組分組合的含㈣㈣〇酸#油_,^ 作單酿基甘油。單酸甘油,旨為在三酸甘油酿及二酸甘沿 分解時在體内形成之正常冲謝板 τ ( ¥代謝物。正如所述,含有脂助 之單酸甘油酯可與脂肪酸έ分 嘅!刀(諸如如下文所述之脂肪 161219.doc 201233342 及/或脂肪酸鹽)組合包含於營養品中,或可在不存在脂肪 酸組分之情況下包含於營養品中。 適合用於營養品中之含有脂肪酸之單酸甘油酯可包含具 有4至22個碳原子之鏈長度的脂肪酸,包括具有14至20個 . 碳原子之鏈長度的脂肪酸,且包括棕櫊酸(16個碳原子)。 尤其較佳為單酸甘油酯,其中單酸甘油酯中至少70%之脂 肪酸位於Sn-Ι位置’包括在811_丨位置(亦稱作α位置)處具有 至少約70%之棕櫊酸殘基的單棕櫚酸甘油酯,包括在Sn_ i 位置處至少約80%,且包括在sn-l位置處約85%至約 1 00%。此外’在某些實施例中,本文所述營養品中包含 之單酸甘油酯可包括痕量之二酸甘油酯、游離甘油及/或 游離脂肪酸。如本文中所用,術語「痕量」意謂不超過1 〇 wt% ’但更通常小於7.5 wt%之量。 在一個特定實施例中,營養品中之單酸甘油酯(且視情 況為如下文論述之脂肪酸組分)部分地或完全經由使用水 解豬油或水解動物脂來向產品提供。豬油、動物脂及其他 基於動物之產品可添加至營養品甲且由胰腺脂肪酶水解為 單酸甘油酯及脂肪酸。或者,豬油或動物脂可經水解之後 - 併入營養品中以產生單酸甘油酯及脂肪酸,其可引入營養 - 品中。豬油、動物脂或水解豬油或動物脂可提供營養品中 之一部分或所有單酸甘油酯及/或脂肪酸。 在另一實施例中,營養品中之單酸甘油酯部分或完全源 自油類’諸如植物油、水產動物油、魚油、海藻油、真菌 油、樹贿及其組合。舉例而言,適合之植物油包括橄欖 161219.doc 15· 201233342 油、芥花籽油(canola oil)、玉米油、棕櫊油' 大豆油 (soybean oil)及其組合。 含有脂肪酸之單酸甘油酯以按營養品中包含之脂肪組分 計至少約10重量%之量存在於營養品中,包括以營養品中 包含之脂肪組分計至少約15重量%,包括以營養品中包含 之脂肪組分計至少約20重量。/。,包括以營養品中包含之脂 肪組分計12重量%至45重量%、包括15重量❶/。至25重量。/〇且 包括約1 0重量%、包括約丨5重量%、包括約2〇重量% '包 括約25重量。/〇、包括約3〇重量。/。且進一步包括約35重量 0/〇、或甚至約40重量%、或甚至約50重量%、或甚至約6〇 重量°/。、或甚至約70重量。/〇、或甚至約80重量。/〇、或甚至 約90重量% '或甚至約100重量〇/〇。 在一個特定實施例中,當營養品為包含約28%(以營養粉 末之重量計)脂肪組分之營養粉末時,含有脂肪酸之單酸 甘油Sa以約1 〇°/。(以脂肪組分之重量計)之含量存在,或每 100公克營養粉末約2.8公克含有脂肪酸之單酸甘油酯。 在另特疋實施例中,當營養品為包含約3.67%(以即食 型營養液體之重量計)脂肪組分之即食型營養液體時,含 有脂肪酸之單酸甘油酯以約10%(以脂肪組分之重量計)之 含量存在,或每1〇〇公克即食型營養液體約〇 367公克含有 脂肪酸之單酸甘油酯。 在另一特定實施例中,當營養 品為包含約7.34°/。(以濃縮201233342 VI. DESCRIPTION OF THE INVENTION: TECHNICAL FIELD OF THE INVENTION The present invention relates to a nutritional product containing pre-digested fat and a method for using the nutritional product. More particularly, the present invention relates to infant, toddler and pediatric products comprising a fatty acid containing monoglyceride and/or fatty acid component that provides nutritional benefits including improved digestion, tolerance and nutrient absorption, and reduced necrosis The incidence of enterocolitis, abdominal pain and short bowel disease. For the application of the relevant application, reference is made to US Provisional Application No. 61/428,168, filed on December 2, 2010, filed on December 2, 2010, and US Provisional Application No. 61/428,173, filed on December 29, 2010 U.S. Provisional Application No. 61/428,177, filed on December 29, 2010, and US Provisional Application No. 61/428,177, filed on December 29, 2010, and December 29, 2010 The benefit of the benefit of the '61, 428, 185' is incorporated herein by reference in its entirety. [Prior Art] Nutrient liquids and powders (including infant and pediatric formulas) containing targeted nutrients are well known and widely available, one of which provides a single source of nutrition, while others provide supplemental sources. Such nutrients include powders that can be reconstituted with water or other aqueous liquids, as well as concentrated and ready-to-drink nutrient liquids, such as milk or protein based emulsions. These nutrient liquids are especially useful when formulated with selected nutrients. Although breast milk is generally considered to be the best nutrition for newborn babies, not every 161219.doc 201233342 mothers can successfully breastfeed. Breastmilk substitutes (infant formulas) provide complete nutrition and have been shown to meet normal growth and developmental nutritional needs of infants. Unfortunately, a small proportion of infant formula-fed newborns may experience gastrointestinal (GI) intolerance problems, including soft stools, flatulence, necrotizing enterocolitis, abdominal pain, and the like. The problem of GI intolerance can be attributed, at least in part, to incomplete digestion and absorption of nutrients by infants. To address this tolerability problem, some infant formulas exclude lactose as a component' while others replace the intact milk protein with hydrolyzed proteins to reduce the burden on the infant's digestive system. In addition, some formula-fed newborn babies have a much lower rate of fat absorption than breast-fed babies. This difference in fat absorption rate decreases as the baby matures. It is speculated that newborn babies lack lipase and therefore cannot digest and absorb fat as well as breastfed babies who receive lipase from breast milk. The digestive system of premature infants is less developed than the digestive system of full-term infants, which requires more nutrients (calories) than full-term infants to promote growth and development. Medium chain triglycerides (MCT oils) are easily digested and absorbed and are included in preterm formulas to improve formula fat, protein and calcium absorption. However, medium chain fatty acids contained in medium chain triglycerides are not used to re-synthesize triglycerides to form chylomicrons after digestion and absorption of MCT oil. Because many of the fat-soluble nutrients (such as carotenoids and vitamins A, D'E and K) are encapsulated into chylomicrons before entering the systemic circulation, the benefits of MCT oils for fat-soluble nutrient absorption (for growth) And development is also important) may be subject to more restrictions. 161219.doc 201233342 Despite attempts to address (10) and other issues mentioned above in the past, it is desirable to provide good nutritional properties and digestion that provide nutritive benefits similar to breast milk and also provide water-insoluble hydrophobic nutrients. Absorption and infant and pediatric formulations that reduce the incidence of conditions such as necrotizing enterocolitis, abdominal pain and short bowel disease. In addition, it would be beneficial if the formulations were free of stabilizers and in particular no carrageenan. SUMMARY OF THE INVENTION The present invention relates to nutritional products, and in particular to infant formulas, which comprise pre-digested fats. The pre-digested fat comprises a mono-glycolic vinegar and/or a fatty acid component comprising a fatty acid. These nutritional compositions can be advantageously used to improve the tolerance, digestion and absorption of nutrients (including water-insoluble/fat-soluble nutrients), and to reduce the incidence of necrotizing enterocolitis and gastrointestinal ileum. In certain embodiments, the fatty acid component can be in the form of a fatty acid, or in the form of a phosphonium salt or a lock salt of a fatty acid, which provides other benefits of other nutrients. - A method for reducing the incidence of necrotizing enterocolitis in infants, young children or children includes identifying infants, children or children susceptible to necrotizing enterocolitis and administering to the infant, toddler or child A nutrient comprising at least 10 Wt% of at least one free fatty acid component, a fatty acid containing monoglyceride, or a combination thereof. Another embodiment is a method of reducing the incidence of abdominal pain in an infant, toddler or child. The method comprises identifying an infant, a child or a child susceptible to abdominal pain and administering to the infant, toddler or child at least one free fatty acid component comprising at least 1% by weight, a fatty acid-containing monoglyceride or a combination thereof Camp 1612l9.doc 201233342 products. Another embodiment is a method of reducing the incidence of short bowel disease in infants, young children or children. The method comprises identifying an infant, a child or a child susceptible to blight and administering to the infant, toddler or child at least one free fatty acid component comprising at least 10% by weight of a fatty acid containing fatty acid or a combination thereof. Nutritional Products It has been found that nutrients (such as infants, toddlers, and pediatric formulas) containing pre-digested fats (such as monoglycerides and fatty acids as described herein) can reduce the overall burden of the baby's fat digestive system to improve infant fat digestion. And absorption, including the absorption of water-insoluble/fat-soluble nutrients. In particular, the absorption of pre-digested fat in the proximal part of the small intestine stimulates CCK secretion, which promotes pancreatic alpha-cell maturation and digestive enzyme secretion. In addition, GLP-1 and GLP-2 secretion are stimulated. This further promotes intestinal maturation. Surprisingly, the use of pre-digested fat and subsequent secretion of CCK and GLP-1 delays GI transport and stimulates pancreatic enzyme secretion to allow nutrient digestion and absorption to be more complete. A decrease in the amount of nutrients entering the infant's colon leads to a decrease in colonic fermentation, which is partly responsible for the problem of flatulence and soft stools. In addition, the use of pre-digested fat has been found to reduce the incidence of necrotizing enterocolitis, abdominal pain and/or short bowel disease. In addition, it has been discovered that the pre-digested fatty unsaturated fatty acid component can be reacted with a calcium or magnesium source and the resulting salt is surprisingly bioavailable. In addition to providing a good source of calcium or magnesium, these calcium or magnesium salts are also surprisingly milder than fatty acids which generally have a bitter taste and impart a strong burning sensation in the throat. In addition, it has been found that fatty acid calcium or magnesium salts surprisingly act to stabilize the emulsion of 161219.doc 201233342 'this is because it does not form sediments that are difficult to disperse in the emulsion'. Many insoluble calcium salts. Thus, in various embodiments, the inclusion of a fatty acid calcium or magnesium salt as part of the pre-digested fat may reduce the need for stabilizers such as keratin. [Embodiment] The nutritional products described herein include pre-digested fat. In various embodiments, the products comprise a fatty acid containing monoglyceride and a fatty acid component such that the pre-digestible fat system comprises two components. By reducing the burden on the digestive system of infants, toddlers or children, multiple benefits can be realized while providing a stable bioavailable product. These and other features of the nutritional product, as well as a variety of variations, as appropriate, and some of the additions are described in detail below. The terms "sterilization dad package" and "sterilization dad sterilization" are used interchangeably herein and, unless otherwise stated, refer to filling a container with a nutrient liquid (most preferably a metal can or other similar package) and then filling the liquid with liquid. The package is subjected to the necessary thermal sterilization steps to form a common operation of the sterilized sterilizer-encapsulated nutritional liquid product. Unless otherwise established, the term "aseptically packaged" as used herein does not rely on the above described sterilization step to produce a packaged product in which the nutritional liquid and package are separately sterilized prior to filling and subsequently subjected to sterilization or aseptic processing conditions. Combine to form a sterilized, aseptically packaged nutritional liquid product. "Unless otherwise stated, the term "fat" as used herein and used interchangeably refers to a phytochemical derived from or processed by a plant or animal. These terms also encompass synthetic lipid materials as long as the 161219.doc 201233342 substance is suitable for human oral administration. The term "storage stable" as used herein, unless otherwise indicated, means that it is packaged and subsequently stored at 18_24t: for at least 3 months (including from about 6 months to about 24 months) and also contains about 12 months to about Commercially stable nutritional products after 18 months). The terms "nutritional formulation" or "nutraceutical" or "nutritional composition" as used herein are used interchangeably and, unless otherwise indicated, mean liquid and solid (including semi-liquid and semi-solid) human milk fortifiers, liquids. And solid preterm formula, liquid and solid infant formula, liquid and solid second stage formula, liquid boat and solid pediatric formula, and liquid and solid infant formula. The solids can be a powder that can be reconstituted to form a nutrient liquid, all of which include one or more of fats, proteins, and carbohydrates and are suitable for oral administration to humans. The term "nutritional liquid" as used herein, unless otherwise indicated, refers to a nutrient in the form of a ready-to-drink, in a concentrated form, and a nutritional liquid prepared by reconstituting the powder of the form (4) herein prior to use. The term "nutritional powder" as used herein, unless otherwise indicated, refers to a nutrient in a flowable or self-contained form that can be reconstituted with water or another aqueous liquid prior to administration' and includes spray drying and dry mixing/dry mixing. Powder Unless otherwise stated, the term "baby" used in the term "Just" refers to a person who is older or younger. The term "premature baby" as used in this article is an infant born before 36 weeks of pregnancy. Unless otherwise stated, the term "young child" as used herein, as used herein, means 1612l9.doc 201233342 to three years old. The term "child" as used herein, unless otherwise indicated, refers to a person between the ages of three and twelve. Unless otherwise stated, the term "pre-digested fat" as used herein refers to a monoglyceride and/or fatty acid component containing a fatty acid. - The term "infant formula" as used herein, unless otherwise indicated, refers to liquid and solid nutritional supplements suitable for use as a primary source of nutrients for infants. Unless otherwise stated, the term "preterm formula" as used herein is a liquid and solid nutrient σσ 0 that is suitable for use as a primary source of nutrition for preterm infants. Unless otherwise stated, the term "human milk fortifier" is used herein. Liquid and solid nutritional supplements that are suitable for mixing with breast or premature formula or infant formula for preterm or full-term infants. The term "monoglyceride containing a fatty acid" as used herein, unless otherwise indicated, refers to one of the positions of Sn-Wa, 8η·2(β) or Sn_3(a,) of a glycerol molecule via an ester bond. A glyceride consisting of a fatty acid bond covalently bonded to a glycerol molecule. The term "fatty acid component" as used herein, unless otherwise indicated, refers to a free fatty acid or fatty acid salt derived from a source in which the total amount of myristic acid, palmitic acid, and stearic acid is less than 2% by weight (by weight). Such as fat or magnesium salt). Λ Unless otherwise stated, the term "fat-soluble nutrients" as used herein refers to water-insoluble nutrients such as oil-soluble (fat-soluble) vitamins (eg vitamins A, D, £ and 1 (:), carotenoids (eg Lutein, 161219.doc 201233342 β 萝 _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Each of the numerical values and numerical sub-sets are intended to be included within the scope of the disclosure. In addition, the numerical range should be construed as supporting the claim of any value or sub-set of the range. For example, the disclosure of 1 to 10 should be It is understood to support the range of 2 to 8, 3 to 7, 5 to 6' 1 to 9, 3.6 to 4.0, 3.5 to 9·9, etc. Unless otherwise stated or clearly contradicted in the context of the reference, otherwise All singular features or limitations of the singular singular singular singular singular singular singular singular singular singular singular singular singular singular singular singular singular singular singular singular singular singular Or process step combination The various embodiments of the nutritional products of the present invention may also be substantially free of any of the conditions described herein or selected components or features that are limited to the rest of the article! The nutrient should still contain as herein All the required ingredients or characteristics are described. In this context, 'unless otherwise stated', the term "substantially absent" means that the selected nutrient contains less than the functional amount of the component as the case exists, generally less than the weight / 〇 (Including less than 〇 5% by weight 'containing less than 〇 重量 % by weight and also containing 丨 by weight %) of the conditionally present or selected ingredients. Nutrients and methods may include product elements as described herein and Or otherwise suitable for, or consist essentially of, any of the elements of the nutritional and method application. Product form 161219.doc -10- 201233342 The pre-digested fat containing nutrient of the present invention Related methods can be formulated and performed in any form of oral product known or otherwise suitable. Any solid, semi-solid, liquid, semi-liquid or powder form (including combinations thereof) Variants are hereby incorporated by reference to the extent that the <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; Fat. These products may optionally contain a combination of fatty acid-containing monoglycerides or fatty acid components with other fat sources as described below. Products such as Hai may contain the ingredients described herein and are safe and effective for oral administration. Any of the product forms. The nutritional products may be formulated to contain only the ingredients described herein, or may be modified with the ingredients as appropriate to form a plurality of different product forms. The nutritional products of the present invention are preferably formulated as dietary products. Forms thereof are defined herein as such embodiments of the compositions of the present invention in the form of a product which thus contains at least one of fats, proteins and carbohydrates, and preferably also vitamins, minerals or combinations thereof. In various embodiments, the product will include a combination of pre-digested fat with protein, carbohydrates, vitamins and minerals to produce a nutritional product. One such nutraceutical may be formulated with a sufficient variety and amount of nutrients to provide a single primary or supplemental source of nutrition, or to provide an individual dedicated to a particular disease or condition or a nutritional product having a targeted nutritional benefit. By way of example, specific non-limiting examples of product forms suitable for use with the pre-digested fats disclosed herein include liquid and powdered human milk fortifiers, liquid and powdered preterm formulas, liquid and powdered infant formulas, I6l2l9 .doc •11 · 201233342 Liquid and powdered ingredients and semi-element formulas, liquid and powdered pediatric formulations, and liquid and powdered infant formulas. Nutrient Liquids Nutrient liquids contain concentrated and ready-to-eat nutrient liquids. These nutrient liquids are most commonly formulated as suspensions or emulsions. Suitable nutritional emulsions can be aqueous emulsions containing proteins, fats and carbohydrates. The emulsions are typically flowable or drinkable liquids at about to about 25 ° C and are typically in the form of oil-in-water, water-in-oil or complex aqueous emulsions. However, such emulsions most generally have a continuous aqueous phase and discontinuous The oil phase is in the form of an oil-in-water emulsion. The nutritional emulsion can be stable to storage and generally stable to storage. These nutritional emulsions typically contain up to about 95 weight percent based on the weight of the nutritional emulsion. The water of the crucible includes from about 50% by weight to about 95% by weight of rhodium, and also includes from about 60% by weight to about 90% by weight of 'and also including from about 7% by weight to about 88% by weight of water. The nutritional emulsion can have a variety of product densities, but most typically has a density greater than about 丨〇3 g/ml 'including greater than about 1.04 g/mi, including greater than about 1.055 g/ml' including from about 1.06 g/ml to about 1.12 g. /ml, and also includes from about 1.085 g/ml to about 1.10 g/ml. The nutritional emulsion can have a caloric density tailored to meet the nutritional needs of the end user's. However, in most cases the emulsions typically comprise at least 19 kcal/fl oz (660 kcal/liter), more typically about 2 〇. Kcal/fl oz (675-680 kcal/litre) to approximately 25 kcal/fl 〇z (820 kcal/litre), and even more generally approximately 20 kcal/fl 〇z (675-680 kcal/litre) to Approximately 24 kcal/fl oz (800-810 kcal/litre). In general, 22-24 kcai/n 〇z (74〇_81〇161219.doc -12- 201233342 kcal/litre) formula is more commonly used in preterm or low birth weight infants, and 20-21 kCal/fl OZ (675-680 to 7 〇〇 kcal / liter) formula is more commonly used in term infants. In certain embodiments, the emulsion can have a caloric density of from about 1 kilocalyptus per liter to about 660 kilocalories per liter, including from about 15 kilocalories per liter to about 5 kilocalories per liter. The nutritional emulsion may have a 1) 11 value in the range of from about 3.5 to about 8, but most advantageously from about 4.5 to about 7.5, including from about 55 to about 7.3, including from about (a) to about 7.2. While the amount of nutritional emulsion to be administered can vary depending on a variety of variables, typical dosages will generally be at least about 2 mL, or even at least about 5 mL, or even at least about 10 mL, or even at least about 25 〇1 including about 2 mL to about The range of 3(9) is about 4 mL to about 250 mL, and includes about 1 〇mL to about 240 mL. As noted above, the nutritional product may also be in a semi-liquid form, including such forms in which the properties (such as flow characteristics) are intermediate (between the liquid and the solid). Examples of non-volatile semi-liquids include viscous shakes and liquid gels. Nutritional Solids The nutritional solids can be in any solid form, but are generally in the form of a flowable or substantially flowable particulate composition, or at least a particulate composition. Especially suitable. The nutritional solid product form comprises a spray dried, poly, knot or dry blended powder composition. The compositions can be readily consulted or measured similarly to other devices wherein the compositions can be readily reconstituted by the intended user with a suitable aqueous liquid (typically water) to form a nutritional formulation for immediate use. Oral or enteral use. In this context, "immediately" is usually used within the meaning of I61219.doc 201233342, which is preferably within about 48 hours after recovery, most typically within about 24 hours. The nutritional powder can be reconstituted with water prior to use to a caloric density tailored to meet the end user's nutritional needs. However, in most cases the powder is reconstituted with water to form at least 19 kcal/fl oz (660 kcal/liter). )' More generally about 20 kcal/fl 〇z (675-680 kcal/litre) to about 25 kcal/fl oz (820 kcal/liter)' or even more generally about 20 kcal/fl OZ (675-680) From kcal/liter to a composition of about 24 kcal/fl 〇z (800-810 kcal/liter). In general, 22-24 kcal/fl oz (740-8 10 kcal/litre) formula is more commonly used in premature or low birth weight infants, and 2〇_21 kcal/fl oz (675-680 to 700 thousand) Card/liter formula is more commonly used for term infants. In some embodiments, the reconstituted powder can have a caloric density of from about 5 kcal/liter to about 66 kcal/liter, including about! 〇〇 kcal / liter to about 5 〇〇 kcal / liter. As noted above, the nutritional product may also be in a semi-solid form, including such forms as properties (such as stiffness) in the intermediate state (between the solid and the liquid). Some semi-solid examples include puddings, gelatin, and creams. Pre-digested fat system A. Monoglyceride containing fatty acid. In certain embodiments, the nutritional product of the present invention comprises (tetra)(tetra)decanoic acid#oil_, ^ alone or in combination with the fatty acid component as described in 1. Brewed glycerin. Monoglyceride, which is designed to form a normal flushing plate in the body when triglyceride is brewed and decomposed along the disaccharide. (The metabolite. As mentioned, the monoglyceride containing the fat can be separated from the fatty acid. A combination of a knife (such as fat 161219.doc 201233342 and/or a fatty acid salt as described below) is included in the nutrient or may be included in the nutrient in the absence of the fatty acid component. The fatty acid-containing monoglyceride may comprise a fatty acid having a chain length of 4 to 22 carbon atoms, including a fatty acid having a chain length of 14 to 20 carbon atoms, and includes palmitic acid (16 carbon atoms). Particularly preferred is a monoglyceride wherein at least 70% of the fatty acids in the monoglyceride are located at the Sn-Ι position and include at least about 70% palmitate at the 811_丨 position (also referred to as the alpha position). The residue of monopalmitin comprises at least about 80% at the Sn_i position and includes from about 85% to about 100% at the sn-1 position. Further, in certain embodiments, the nutrition described herein The monoglyceride contained in the product may include trace amounts of diglyceride Oil ester, free glycerol and/or free fatty acid. As used herein, the term "trace" means an amount not exceeding 1 〇 wt% 'but more typically less than 7.5 wt%. In a particular embodiment, in a nutraceutical The monoglyceride (and optionally the fatty acid component as discussed below) is supplied to the product, either partially or completely via the use of hydrolyzed lard or hydrolyzed animal fat. Lard, animal fat and other animal based products may be added to the nutrient. The nail is hydrolyzed by the pancreatic lipase to a monoglyceride and a fatty acid. Alternatively, the lard or tallow can be hydrolyzed - incorporated into the nutrient to produce a monoglyceride and a fatty acid which can be incorporated into the nutrient. Lard, tallow or hydrolyzed lard or tallow may provide a portion or all of the monoglycerides and/or fatty acids in the nutrient. In another embodiment, the monoglyceride in the nutrient is partially or completely derived Oils such as vegetable oils, aquatic animal oils, fish oils, seaweed oils, fungal oils, tree bribes, and combinations thereof. For example, suitable vegetable oils include olive 161219.doc 15· 201233342 oil, canola Oil (canola oil), corn oil, palm oil, soybean oil, and combinations thereof. The fatty acid-containing monoglyceride is present in an amount of at least about 10% by weight based on the fat component contained in the nutritional product. The nutrient comprises at least about 15% by weight based on the fat component contained in the nutrient, and comprises at least about 20% by weight of the fat component contained in the nutrient, including the fat component contained in the nutrient. From 12% by weight to 45% by weight, including 15% by weight to 25 parts by weight, and including about 10% by weight, including about 5% by weight, including about 2% by weight, including about 25 weights. Including about 3 〇 weight. /. And further comprising about 35 weights per ounce, or even about 40 weight percent, or even about 50 weight percent, or even about 6 weight percent. Or even as much as 70 weight. /〇, or even about 80 weight. /〇, or even about 90% by weight 'or even about 100% 〇/〇. In a particular embodiment, when the nutritional product is a nutritional powder comprising about 28% (by weight of the nutritional powder) of the fat component, the fatty acid-containing monoglyceride Sa is about 1 〇 ° /. The content (by weight of the fat component) is present, or about 2.8 grams of the fatty acid monoglyceride per 100 grams of nutritional powder. In another special embodiment, when the nutritional product is a ready-to-eat nutritional liquid comprising about 3.67% (by weight of the ready-to-feed nutritional liquid) of the fat component, the fatty acid-containing monoglyceride is about 10% (by fat). The content of the component is present in the amount of, or about 367 grams of the nutrient-containing nutrient liquid per gram of the monoglyceride containing the fatty acid. In another specific embodiment, when the nutrient is comprised, it comprises about 7.34 ° /. (to concentrate

161219.doc '養液體時,含 分之重量計)之 •16· 201233342 a量存在,或每loo公克濃縮型營 土 s脣液體約0.734公克含有 脂肪酸之單酸甘油酯。 a兄3书 :提供上文所列之多種益處以外,亦已發現含有脂肪酸 之=酸甘油醋在營養品中具有抗病毒及/或抗細菌活性。 特定而言’已發現營養品中含有脂 0頁知肪酸之單酸甘油酯之存 在能殺死病原體及/或減緩其複製。 B.脂肪酸組分 除上述含有脂肪酸之單酸甘油酯 甘泊S日以外,或替代上述含有 脂肪酸之單酸甘油8旨,本發明之營養品可包含含有脂肪酸 之脂肪酸組分作為預消化脂肪系統之一部分。脂肪酸為在 脂肪(三酸甘油酯、二酸甘油酯、膽固醇酯及某些磷脂)分 解時在體内顯著形成之正常代謝物。該脂肪酸組分為獨立 的且不同於上文論述之含有脂肪酸之單酸甘油酿。 在營養品中有益之任何脂肪酸均可作為預消化脂肪系統 之一部分包含於營養品中。在一個實施例中,脂肪酸為不 飽和游離脂肪酸。在包含不飽和游離脂肪酸之某些實施例 中’具有超過14個碳原子之鏈長度的不飽和游離脂肪酸之 總量小於1 5 wt%。適合包含於本文所述營養品中之例示性 脂肪酸包括(但不限於)花生四烯酸、次亞麻油酸、二十二 碳六稀酸、十八碳四稀酸、油酸、二十碳稀酸、二十碳三 烯酸(mead acid)、芥酸、神經酸以及其混合物及組合。尤 其較佳之脂肪酸包括花生四烯酸、亞麻油酸、次亞麻油 酸、二十二碳六烯酸及油酸。 包含於預消化脂肪系統中之脂肪酸組分包括源自諸如植 161219.doc 201233342 物油、水產動物油、魚油、海藻油、真菌油、動物脂肪、 動物脂肪分離物及其組合之油類的彼等脂肪酸組分。舉例 而言,適合之植物油包括橄禮油、芬花籽油、玉米油、大 豆油及其組合。在一個實施例中,當使用動物脂肪時,脂 肪酸係由猪油或動物脂之酶促水解而獲得,且所得脂肪酸 混合物中掠棚酸及硬脂酸之含量減少至小於總脂肪酸之 20%,包括小於總脂肪酸之2%。在另一實施例中,至少一 些脂肪酸源自大豆油或樹脂。一旦源自油來源,則脂肪酸 實質上不含單酸甘油酯、二酸甘油酯及三酸甘油酯。 脂肪酸通常將源自含有小於約20°/。(以重量計)棕櫊酸及/ 或硬脂酸及/或肉豆蔻酸之源油。在某些實施例中,脂肪 酸將源自含有小於約15%(以重量計)、包括小於約10%(以 重量計)、包括小於約5%(以重量計)且包括小於2%(以重量 計)棕搁酸及/或硬脂酸及/或肉豆蔻酸之源油。 在一個特定實施例中,脂肪酸係源自含有小於約20%(以 重量計)’包括約10°/。(以重量計)至約15%(以重量計)棕橺 酸及/或硬脂酸及/或肉豆蔻酸之源油。在另一特定實施例 中’營養品包含以總脂肪酸計小於約10%(以重量計)之量 的棕櫚酸。 在某些實施例中,營養品可包含呈鹽形式之脂肪酸;亦 即’脂肪酸可以脂肪酸鹽形式添加至營養品中。在一個適 合的實施例中’脂肪酸係以脂肪酸鈣鹽、脂肪酸鎂鹽或其 紐·合之形式添加至營養品中。 脂肪酸鹽可由熟習此項技術者基於本文之揭示内容來製 161219.doc -18- 201233342 備。在一種適合的製程中,包含Ci〇_C24脂肪酸鈣鹽之乳液 γ藉由首先藉由使用與至少—種^·^脂肪酸來源混合之 若干種起始鈣來源製備脂肪酸鹽來製備。更特定而言,在 種方法巾’包含呈二酸甘油酯摻合物形式或游離形式的 CI0-C24脂肪酸之起始來源可藉由與氫氧化鈣及/或碳酸鈣 及/或磷酸鈣接觸而形成。在另一種方法中,呈三酸甘油 輯摻合物或游離形式之C,Q_C24脂肪酸可藉由與1311值為6至 約7.5之水合CaCl2或Ca(AcO)2接觸而製得。 以上方法可在惰性氛圍下,例如在沁或氬氣下進行。在 其他實例巾’任何所揭示之方法均可在環境氛圍下進行 (例如,其中不在低氧氛圍下進行反應)。 包含C10-C24脂肪酸之來源與鈣來源可藉由此項技術中已 知之任何方法來混合。「混合」並非意謂暗示特定混合結 果,諸如任何組分溶解至特定程度或形成特定組合物(諸 如均質混合物),不過可產生該等混合物且某些組分可藉 由混合而溶解。混合可為劇烈的且可手動或藉由機械裝置 (諸如(但不限於)靜態混合器、磁力攪拌器、振盪器、旋轉 器或旋轉裝置)來進行。混合可藉由迫使氣體通過混合物 或使氣體起泡通過混合物或藉由音波處理來進行。161219.doc 'when raising liquid, the weight of the part is included. ·16· 201233342 a quantity is present, or about 0.734 grams of lipopolyglycerol containing fatty acid per gram of concentrated camp soil s lip liquid. a brother 3 book: In addition to the various benefits listed above, it has also been found that fatty acid-containing glycerol vinegar has antiviral and/or antibacterial activity in the nutritional product. In particular, it has been found that the presence of a monoglyceride containing a fat in a nutritional product can kill the pathogen and/or slow its replication. B. Fatty acid component In addition to or in place of the above-mentioned fatty acid-containing monoglyceride 8, the nutritional product of the present invention may comprise a fatty acid component containing a fatty acid as a pre-digested fat system. Part of it. Fatty acids are normal metabolites that are formed in the body when they are decomposed in fats (triglycerides, diglycerides, cholesterol esters, and certain phospholipids). The fatty acid component is independent and different from the monoglyceride containing fatty acids discussed above. Any fatty acid that is beneficial in the nutritional product can be included in the nutritional product as part of the pre-digested fat system. In one embodiment, the fatty acid is an unsaturated free fatty acid. In certain embodiments comprising unsaturated free fatty acids, the total amount of unsaturated free fatty acids having a chain length of more than 14 carbon atoms is less than 15 wt%. Exemplary fatty acids suitable for inclusion in the nutrients described herein include, but are not limited to, arachidonic acid, linoleic acid, docosahexaenoic acid, octadecanoic acid, oleic acid, twenty carbon Dilute acid, mead acid, erucic acid, nervonic acid, and mixtures and combinations thereof. Particularly preferred fatty acids include arachidonic acid, linoleic acid, linoleic acid, docosahexaenoic acid and oleic acid. The fatty acid component contained in the pre-digested fat system includes those derived from oils such as 161219.doc 201233342 oil, aquatic animal oil, fish oil, algae oil, fungal oil, animal fat, animal fat isolates, and combinations thereof. Fatty acid component. For example, suitable vegetable oils include olive oil, fennel seed oil, corn oil, soybean oil, and combinations thereof. In one embodiment, when animal fat is used, the fatty acid is obtained by enzymatic hydrolysis of lard or tallow, and the content of the shed acid and stearic acid in the resulting fatty acid mixture is reduced to less than 20% of the total fatty acid. Includes less than 2% of total fatty acids. In another embodiment, at least some of the fatty acids are derived from soybean oil or a resin. Once derived from the oil source, the fatty acid is substantially free of monoglycerides, diglycerides, and triglycerides. The fatty acid will typically be derived containing less than about 20°/. (by weight) source oil of palmitic acid and / or stearic acid and / or myristic acid. In certain embodiments, the fatty acid will be derived from containing less than about 15% by weight, including less than about 10% by weight, including less than about 5% by weight, and including less than 2% (in terms of Weight) palmitic acid and / or source of stearic acid and / or myristic acid. In a particular embodiment, the fatty acid is derived from less than about 20% by weight of &apos; including about 10°/. (by weight) to about 15% by weight of palmitic acid and/or source of stearic acid and/or myristic acid. In another particular embodiment, the nutritional product comprises palmitic acid in an amount of less than about 10% by weight, based on total fatty acids. In certain embodiments, the nutritional product may comprise a fatty acid in the form of a salt; that is, the fatty acid may be added to the nutritional product in the form of a fatty acid salt. In a suitable embodiment, the fatty acid is added to the nutritional product in the form of a fatty acid calcium salt, a fatty acid magnesium salt or a conjugate thereof. Fatty acid salts can be prepared by those skilled in the art based on the disclosure herein. 161219.doc -18-201233342. In a suitable process, the emulsion gamma comprising the Ci(R) fatty acid calcium salt is prepared by first preparing a fatty acid salt by using several starting calcium sources mixed with at least one of the fatty acid sources. More specifically, the starting source of the CI0-C24 fatty acid in the form of a diglyceride blend or free form can be contacted by calcium hydroxide and/or calcium carbonate and/or calcium phosphate. And formed. In another method, a triglyceride blend or a free form of C, Q_C24 fatty acid can be prepared by contacting CaCl2 or Ca(AcO)2 with a 1311 value of from 6 to about 7.5. The above process can be carried out under an inert atmosphere, for example under helium or argon. In any of the other examples, any of the disclosed methods can be carried out under ambient conditions (e.g., where the reaction is not carried out under a low oxygen atmosphere). The source comprising the C10-C24 fatty acid and the source of calcium can be mixed by any method known in the art. "Mixing" is not meant to imply a particular mixing result, such as the dissolution of any component to a particular degree or formation of a particular composition (such as a homogeneous mixture), but such mixtures may be produced and some of the components may be dissolved by mixing. Mixing can be dramatic and can be done manually or by mechanical means such as, but not limited to, a static mixer, a magnetic stirrer, an oscillator, a rotator or a rotating device. Mixing can be carried out by forcing a gas through the mixture or by bubbling the gas through the mixture or by sonication.

Cio C24知肪酸來源與鈣來源混合可進行至少1分鐘。混 合亦可進行至少卜5、15、2〇、25、3〇、35 4〇45、 5〇、55、60、65、7〇、75、8〇、8卜 9〇、% 或 ι〇〇 分鐘, 其中任何所述值若適當則均可形成上端或下端端點。 混合可在各種溫度下進行,但該方法一般在高溫下發 161219.doc 201233342 生。確切高溫可取決於C1(rC24脂肪酸或鈣之特定起始來源 及其用量。可進行所揭示混合所處之適合溫度包括(但不 限於)約4°c至約100°c、約lot至約100°C、約15°C至約 100°C、或約 20°C 至約 70°C。 包含C〗〇-C24脂肪酸或鈣之來源亦可在混合之前經加熱。 該種預熱步驟可在本文所述之任何溫度或溫度範圍下進 行。 在某些實施例中’ C 10-(:24脂肪酸與鈣之混合可在減壓下 進行。適合壓力小於或等於約1托(Torr)或小於或等於約 0.1托。 在一個理想實施例中,C1()-C24脂肪酸鈣鹽係藉由添加游 離C1()-C24不飽和脂肪酸及鈣來源(諸如Ca(otl)2、CaCl2、 CaC〇3、檸檬酸鈣或該等鹽之混合物)以形成油摻合物來製 備。更特定而言’將脂肪酸溶解於溫熱水溶液(例如,具 有約40°C至約80°C之溫度)中。可使用KOH或NaOH將溶液 之pH值調整至一般為約^丨丨之pH值。隨後向所溶解之含 脂肪酸的溶液中添加鈣。一般使脂肪酸及鈣靜置1〇分鐘以 確保脂肪酸與鈣離子之間完全反應^隨後使混合物均質化 以形成油換合物。 在另一個理想實施例中,製備脂肪酸鈣鹽之混合物(包 括來自魚油、海藻油、真菌油及大豆油(s〇y 〇il)之脂肪酸) 作為預消化脂肪系統之一部分。將魚油、海藻油、真菌油 及大豆油混合在一起且在氮氣層下由氫氧化鉀水解。隨後 向混合物中添加鈣來源(諸如氣化鈣)以與脂肪酸反應而產 161219.doc -20- 201233342 生不溶性脂肪酸鈣鹽。該等不溶性脂肪酸鹽可藉由過渡分 離’且用水洗滌,然後進行真空乾燥。 已令人驚訝地發現,儘管脂肪酸鹽(諸如脂肪酸鈣鹽)通 常不溶於營養品中’但其不會在溶液中沈降而形成難以再 分散之沈降物層。因此,使用脂肪酸鈣鹽及/或脂肪酸鎮 鹽使得鈣/鎂傳遞更佳’且在多個實施例中可消除對於其 他穩定劑(諸如角又菜勝)之需求,以使得產品可實質上或 完全「無角又菜膠」。 因此’與使用磷酸鈣或碳酸鈣作為鈣來源之產品相比, 使用脂肪酸鹽使得鈣及/或鎂及脂肪酸生物可用性得以改 善。 此外’已發現在本發明之營養品中使用脂肪酸鹽提供生 物可用性脂肪酸’諸如花生四烯酸(ARA)及其類似物,其 顯示增強嬰兒生長。使用預消化脂肪亦提供具有經改善之 產品穩定性及較長存放期之乳狀營養品。 營養品通常包含按營養品中包含之脂肪組分計至少約 10%(以重量計)之量的脂肪酸或脂肪酸鹽,包括按營養品 中包含之脂肪組分計至少約丨5重量。/。、包括至少約2〇重量 °/〇、包括約10重量。/。至約60重量。/。、包括約15重量%至約40 重量%,且包括約15重量%至約35重量%、包括約1〇重量 %、包括約1 5重量。/〇、包括約20重量%、包括約25重量0/〇、 包括約30重量%、包括約35重量❶/〇且進一步包括約40重量 %、或甚至約50重量%、或甚至約60重量%、或甚至約7〇 重量%、或甚至約80重量%、或甚至約90重量%、或甚至 161219.doc •21 - 201233342 約100重量%。 在某些實施例中,營養品包含脂肪酸組分與含有脂肪酸 之單酸甘油酯的混合物。在該等實施例中,營養品含有按 營養品中包含之脂肪組分計至少i 0%(以重量計)之量的混 合物’包括按營養品中包含之脂肪組分計至少約i 5重量 %、包括至少約20重量%、包括約丨〇重量%至約40重量%、 包括約20重量%至約65重量。/。、包括約25重量%至約50重 量%、包括約15重量%至約3〇重量%,且包括約15重量%至 約25重量%、包括約1 〇重量%、包括約丨5重量%、包括約 20重量°/。、包括約25重量❶/。、包括約3〇重量%、包括約3 5 重量%,且進一步包括約4〇重量%或甚至約50重量%、或 甚至約60重量%、或甚至約7〇重量%、或甚至約8〇重量 %、或甚至約90重量%或甚至約i 〇〇重量〇/〇。 在其他實施例申’營養品包含以營養品中總乾物質計至 少0.2%(以重量計)、包括至少1%(以重量計)、包括至少 2%(以重量計)且包括至少5%(以重量計)之量的脂肪酸組 分、含有脂肪酸之單酸甘油酯或其組合。 常量營養素(Macronutrient) 儘管脂肪、蛋白及碳水化合物之總濃度或量可視產品類 型(亦即,人乳強化劑、嬰兒配方等)、產品形式(亦即,營 養固體、粉末、即食型液體或濃縮型液體)及預期使用者 之目標飲食需求而變化,但該等濃度或量最一般在以下具 體範圍H包括如本文所述之任何其他脂肪、蛋白及/ 或碳水化合物成分。 1612I9.doc -22- 201233342 對於液體早產及足月嬰兒配方產品而言,以早產或足月 嬰兒配方之重量計,碳水化合物濃度最一般在約5 %至約 40%、包括約7%至約30%、包括約1〇〇/0至約25%之範圍 内;以早產或足月嬰兒配方之重量計,脂肪濃度(包括預 消化脂肪與任何其他脂肪來源)最一般在約1。/❶至約30〇/〇、 包括約2°/。至約1 5%以及包括約30/。至約10%之範圍内;且以 早產或足月嬰兒配方之重量計,蛋白濃度最一般在約〇.5〇/0 至約30。/。、包括約1%至約15°/。以及包括約2%至約10%之範 圍内。 對於液體人乳強化劑產品而言,以人乳強化劑之重量 計’碳水化合物濃度最一般在約1 〇%至約75%、包括約 10%至約50%、包括約20%至約40%之範圍内;以人乳強化 劑之重量計,脂肪濃度(包括預消化脂肪與任何其他脂肪 來源)最一般在約1 0°/〇至約40°/。、包括約1 5%至約37°/。以及 包括約1 8%至約30%之範圍内;且以人乳強化劑之重量 計’蛋白濃度最一般在約5%至約40%、包括約1 〇%至約 30%以及包括約15%至約25%之範圍内。 除了如下表所列的營養品中之總熱量百分比以外或作為 其替代,亦表徵液體營養品中碳水化合物、脂肪及/或蛋 白之含量或量。用於本發明液體營養品之該等常量營養素 最一般在下表所述之任何熱量範圍内(實施例A-F)調配(每 一數值之前均有術語「約」)。 161219.doc -23- 201233342 營養素總熱量% 實施例A 實施例B 實施例C 碳水化合物 0-98 2-96 10-75 蛋白 0-98 2-96 5-70 脂肪 0-98 2-96 20-85 實施例D 實施例E 實施例F 竣水化合物 30-50 25-50 25-50 蛋白 15-35 10-30 5-30 脂肪 35-55 1-20 2-20 在一個特定實例中,液體嬰兒配方(即食型與濃縮型液 體)包括彼等實施例,其中蛋白組分可構成配方之約7·5% 至約25%之熱量含量;碳水化合物組分可構成嬰兒配方之 約35%至約50%之總熱量含量;且脂肪組分可構成嬰兒配 方之約30%至約60%之總熱量含量。該等範圍僅作為實例 提供,且不欲具限制性。下表中列舉其他適合範圍(每一 數值之前均有術語「約」)。 營養素總熱量% 實施例G 實施例Η 實施例I 碳水化合物: 20-85 30-60 35-55 脂肪= 5-70 20-60 25-50 蛋白: 2-75 5-50 7-40 當營養品為粉末型早產或足月嬰兒配方時,以早產或足 月嬰兒配方之重量計,蛋白組分以約5%至約35%、包括約 8%至約12%且包括約10%至約12%之量存在;以早產或足 月嬰兒配方之重量計,脂肪組分以約10%至約35%、包括 約25%至約30%且包括約26%至約28%之量存在;且以早產 或足月嬰兒配方之重量計,碳水化合物組分以約30%至約 161219.doc -24- 201233342 85/。、包括約45%至約60。/。且包括約5〇%至約55%之量存 在。 對於粉末型人乳強化劑而言,以人乳強化劑之重量計, 蛋白組分以約1%至約55%、包括約1〇%至約5〇%且包括約 1 0 /。至約3 0 /〇之量存在’以人乳強化劑之重量計,脂肪組 分以約1%至約30%、包括約1%至約25%且包括約1%至約 20%之量存在;且以人乳強化劑之重量計,碳水化合物組 分以約15%至約75%、包括約15%至約6〇%且包括約2〇%至 約50°/。之量存在。 脂肪、碳水化合物及蛋白在本發明粉末型營養品中之總 量或濃度可在相當程度上視所選產品及預期使用者之飲食 或醫學需求而變化。下文列舉常量營養素濃度之其他適合 貫例。在此背景下,總量或濃度係指粉末型產品中之所有 脂肪、碳水化合物及蛋白質來源。對於粉末型營養品而 言,該等總量或濃度最一般且較佳在下表所述之任何具體 範圍内調配(所有數值之前均具有「約」)。 營養素總熱量% 實施例J i施例K 碳水化合物 1-85 30-60 35-55 脂肪 5-70 20-60 25-50~~ 蛋白 2-75 5-50 7-40 脂肪 除預消化脂肪以外,本發明之營養品還可包含其他脂肪 來源(脂肪之總量在本文中稱作營養品之「脂肪組分」或 「脂肪系統」)。適合用於本文之其他脂肪來源包括適合 161219.doc -25 201233342 用於口服營養品且可與該等產品之要素及特徵相容之任何 脂肪或脂肪來源。 遍合用於本文所述營養品令之其他脂肪或其來源之非限 制性實例包括椰子油、分餾椰子油、大豆油、玉米油、橄 欖油、紅花籽油 '高油酸紅花籽油、油酸(EMERS〇I^ 6313 油酸)、MCT油(中鏈三酸甘油酯)、向曰葵油、高油酸向日 葵油、棕櫚油及棕櫊仁油、棕櫊油精、芥花籽油、水產動 物油、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包含長鏈聚不飽和脂 肪酸(LC-PUFA ’較佳為具有四個或四個以上雙鍵之 LC-PUFA)之油類及油摻合物。舉例而言,可包含之某些 非限制性特定聚不飽和酸包括二十二碳六烯酸(DHA)、花 生四稀酸(ARA)、二十碳五婦酸(epa)及其類似物。 本文所述之預消化脂肪通常與一種、兩種、三種、四種 或四種以上其他脂肪來源組合包含於營養品中。在一個實 施例中,將單酸甘油酯(理想地為單棕櫚酸甘油酯之形 式)' 脂肪酸(理想地為鈣鹽之形式)、高油酸油及椰子油組 合在一起以提供營養品中之脂肪組分。在該實施例中,以 月曰肪組分之重量計’單酸甘油酯以約1 %至約4〇%(包括約 100/。至約30%,包括約10%、約i5y❶、約2〇%、約23〇/。及約 25%)之量存在;以脂肪組分之重量計,脂肪酸以約i%至 約40%(包括約1〇%至約3〇。/。,包括約1〇0/。、約15%、約2〇〇/0 及約25%)之量存在;以脂肪組分之重量計,高油酸油以約 1 %至約40%(包括約1 〇%至約3〇%,包括約丨〇%、約丨5〇/〇、 161219.doc -26· 201233342 約20°/。、約25%及約30%)之量存在;且以脂肪組分之重量 計,椰子油以約1%至約40%(包括約10%至約30%,包括約 10%、約15%、約17°/。、約20%及約25%)之量存在。 在另一實施例中,將含有脂肪酸之單酸甘油酯(理想地 為單棕櫚酸甘油酯之形式)、脂肪酸組分(理想地為鈣鹽之 形式)、高油酸紅花籽油及椰子油組合在一起以提供營養 品中之脂肪組分。在該實施例中,以脂肪組分之重量計, 單酸甘油酯以約1 %至約40°/。(包括約1 〇%至約3〇%,包括約 10%、約15%、約20%、約23%及約25%)之量存在;以脂肪 組分之重量計’脂肪酸以約1 %至約4〇%(包括約1 〇%至約 30%,包括約10%、約15%、約20%及約25%)之量存在;以 脂肪組分之重量計’高油酸油以約1 %至約4〇%(包括約1 〇% 至約30%,包括約10%、約1 5%、約20%、約25%及約30%) 之量存在;且以脂肪組分之重量計,椰子油以約1 %至約 40%(包括約10%至約30%,包括約10%、約15%、約17%、 約20%及約25%)之量存在。 在另一實施例中,將含有脂肪酸之單酸甘油酯(理想地 為單棕櫚酸甘油酯之形式)、脂肪酸組分(理想地為約鹽之 形式)、高油酸紅花籽油、椰子油、含DHA油及含ARA油 組合在一起以提供營養品中之脂肪組分。在該實施例中, 以脂肪組分之重量計,單酸甘油酯以約1 %至約40%(包括 約10%至約30%,包括約10%、約15%、約20%、約23°/〇及 約25%)之量存在;以脂肪組分之重量計,脂肪酸以約1 〇/〇 至約40%(包括約10%至約30%,包括約10%、約15%、約 161219.doc .27· 201233342 20%及約25%)之量存在;以脂肪組分之重量計,高油酸油 以約1%至約40%(包括約1 〇%至約30%,包括約1 〇%、約 I5%、約20%、約25%及約30%)之量存在;且以脂肪組分 之重量計’椰子油以約1 %至約40%(包括約1 〇%至約3〇%, 包括約10%、約1 5%、約1 7%、約20%及約25%)之量存在。 含DHA油以腊肪組分之重量計以約1 %至約1 〇%(包括約5%) 之量存在且含ARA油以脂肪組分之重量計以約ι%至約 1〇%(包括約5%)之量存在。 在另一實施例中,脂肪組分包含約38%(以重量計)高油 酸紅花籽油、約1 7%(以重量計)椰子油、約23%(以重量計) 單棕橺酸甘油酯、約20%(以重量計)脂肪酸鈣鹽、約 〇.5°/。(以重量計)含DHA油及約1.0。/。(以重量計)含ARA油。 蛋白質 除預消化脂肪以外,本發明之營養品還可視情況進一步 包含蛋白。適用於口服營養品且可與該等產品之要素及特 徵相容之任何蛋白質來源均適合與預消化脂肪組合使用。 適合用於該等營養品中之蛋白或其來源之非限制性實例 包括水解、部分水解或非水解蛋白或蛋白質來源,其可源 自任何已知或另外適合之來源,諸如乳類(例如酪蛋白、 乳清)' 動物(例如肉類、魚肉)、榖物(例如水稻、玉米)、 植物(例如大豆)或其組合。該等蛋白之非限制性實例包括 乳類蛋白分離物、如本文所述之乳類蛋白濃縮物、酪蛋白 :離物、廣泛水解之路蛋白、乳清蛋白、路蛋白納鹽或詞 鹽、全牛乳、部分或完全脫脂乳、大豆蛋白分離物、大豆 161219.doc • 28 - 201233342 蛋白濃縮物等等。 碳水化合物 本發明之營養品可進一步視情況包含適合用於口 、 服營養 品且可與該等產品之要素及特徵相容之任何碳水化人物 適合用於本文所述營養品中之碳水化合物或其來源 限制性實例可包括麥芽糊精、水解或改質殿粉或玉卡; 粉、葡萄糖聚合物、玉米糖漿、玉米糖漿固艚 ^ M 碾自水稻 之碳水化合物、源自豌豆之碳水化合物、源自馬於 、7署之碳 水化合物、木薯、蔗糖、葡萄糖、果糖、乳糖、高果糖 米糖漿、蜂蜜、糖醇(例如麥芽糖醇、赤藻糖醇、山梨= 醇)、人造甜味劑(例如蔗糖素(sucralose)、乙酿續胺酸 鉀、甜菊)及其組合。 其他視情況存在之成分 本發明之營養品可進一步包含其他視情況存在之組分, 其可改變該等產品之物理、化學、美學或加工特徵,1在 用於目標群體時充當醫藥學或其他營養組分。已知多種該 等視情況存在之成分或其另外適用於醫學食 品或醫藥劑型卜且亦可用於本文之组合物中=2: 件為該等視情況存在之組分口服安全且可與選定產品形式 之各成分相容。 該等視情況存在之成分之非限制性實例包括防腐劑、抗 氧化劑、乳化劑、緩衝劑、果募醣、半乳寡醣、益菌助生 質、醫藥活性物、如本文所述之其他營養素、著色劑、調 味劑、增稠劑及穩定劑、乳化劑、潤滑劑等等。 I61219.doc •29· 201233342 營養品可進一步包含甜味劑,較佳包括至少一種糖醇, 諸如麥芽糖醇、赤藻糖醇、山梨糖醇、木糖醇、甘露糖 醇、異麥芽酮糖醇(isolmalt)及乳糖醇,且亦較佳包括至少 一種人造或高效能甜味劑,諸如乙醯磺胺酸K、阿斯巴甜 糖(aspartame)、蔗糖素、糖精、甜菊及塔格糖(tagat〇se)。 該等甜味劑(尤其呈糖醇與人造甜味劑之組合)尤其適用於 調配本發明的具有理想味道型態之液體飲料實施例。該等 甜味劑組合對於遮蔽有時與液體飲料中所添加植物蛋白相 關之不良味道尤其有效。營養品中視情況存在之糖醇渡度 以營養品之重量計可在至少0.01°/。,包括01%至約, 且亦包括約1°/〇至約6%之範圍内。視情況存在之人造甜味 劑濃度以營養品之重量計可在約〇.〇1。/❶,包括約〇 〇5%至約 5%,亦包括約0.1%至約1.0%之範圍内。 流動劑或防結塊劑可包含於如本文所述之營養品中以延 遲粉末隨時間而凝塊或結塊且製得易於自其容器流出之粉 末實施例。已知或另外適用於營養粉末或產品形式之任何 已知流動劑或防結塊劑均適用於本文中,其非限制性實例 包括磷酸三鈣、矽酸鹽及其組合。營養品中流動劑或防結 塊劑之濃度視產品形式、其他所選成分、所要流動特性等 等而變化,但以營養品之重量計最常在約01%至約4%, 包括約0.5%至約2%之範圍内。 穩定劑亦可包含於營養品中。已知或另外適用於營養。 中之任何穩定劑亦適用於本文中’其某些非限制性^例$ 括角叉菜膠及膠類(諸如三仙膠)。以營養品 ^ 〇α $量計,穩 I61219.doc •30- 201233342 定劑可佔約0.1%至約5.0%,包括約〇 5%至約3%,包括約 0.7%至約 1.5%。 營養品組合物可進一步包含任何各種其他維生素或相關 營養素,其非限制性實例包括維生素A、維生素D、維生 素E、維生素K、硫胺素、核黃素、吡哆醇、維生素812、 類胡蘿萄素(例如β-胡蘿_素、玉米黃素、葉黃素、番茄紅 素)、菸酸、葉酸、泛酸、生物素、維生素c、膽鹼、肌 醇、其鹽及衍生物以及其組合。 營養品可進一步包含任何各種其他礦物質,其非限制性 實例包括鈣、磷、鎂、鐵、鋅、錳、銅、鈉、鉀、鉬、 鉻、氣離子及其組合。此外,在某些實施例中,營養品可 不含角又菜膠。 製造方法 本發明之營養品可藉由任何已知或另外可有效於製備所 選產品固體或液體形式之製造技術來製備。已知多種該等 技術可用於任何指定的產品形式(諸如營養液體或粉末), 且很容易由一般熟習此項技術者應用於本文所述之營養 品。 因此’本發明之營養品可藉由任何各種已知或另外有效 之產品或製造方法來製備。舉例而言,在一種適合之製造 製程中’分開製備至少三種漿料,包括脂肪包蛋白質(piF) 漿料、碳水化合物-礦物質(CHO-MIN)漿料及水包蛋白質 (PIW)漿料^ pif漿料係藉由加熱及混合油類(例如單酸甘 油酿及/或脂肪酸、含有脂肪酸之油、芥花籽油、玉米油 161219.doc 31 - 201233342 等)且隨後伴隨持續加熱及攪拌添加乳化劑(例如印麟脂)、 脂肪可溶性維生素及一部分總蛋白(例如,乳蛋白濃縮物 等)來形成。CHO-ΜΙΝ漿料係藉由伴隨加熱授拌向水中添 加以下各物而形成:礦物質(例如檸檬酸卸、碳酸二钟、 檸檬酸鈉等)、痕量及超痕量礦物質(TM/UTM預混物)及/或 增稠劑或懸浮劑(例如晶性纖維素(avicel)、結冷膠 (gellan)、角又菜膠)。使所得CHO-MIN漿料在持續加熱及 揽拌下保持10分鐘,然後添加其他礦物質(例如氣化_、 碳酸鎮、蛾化钟等)及/或碳水化合物(例如果寡膽、蔬糖、 玉米糖漿等)。隨後若還有任何剩餘蛋白質,則藉由伴隨 加熱及攪拌混合來形成PIW漿料。 在本發明之一個特定實施例中’可將營養品中包含之所 有或一部分預消化脂肪添加至CHO-MIN榮料中,該毁料含 有小於5%(以CHO-MIN漿料之重量計)的呈三酸甘油酯形式 之脂肪》在該實施例中’營養品中存在之總脂肪之至少 5〇/〇(以重量計)為預消化脂肪形式且被添加至CHO-MIN漿料 中。在某些實施例中’將營養品中包含之至少5%(以重量 計)、包括至少10°/。(以重量計)、包括至少2〇%(以重量 計)、包括至少30°/。(以重量計)、包括至少4〇%(以重量 計)、包括至少50%(以重量計)、包括至少6〇%(以重量 計)、包括至少70°/。(以重量計)、包括至少8〇%(以重量 計)、包括至少90%(以重量計)且包括wo%(以重量計)之總 預消化脂肪添加至CHO-MIN漿料中。在一個特定實施例 中’在將預消化脂肪添加至CHO-MIN漿料中之前或在製造 161219.doc -32· 201233342 c_IN聚料期間將脂溶性營養素(諸如混合類胡蘿爵素 或維生素A、D、WK)溶解於預消化脂肪中。與阳,嘴料 形成對比’藉由向CH0_MIN激料中添加預消化脂肪,最終 營養組合物之穩定性可得以改善。 隨後伴隨加熱攪拌將所得毁料摻合在-起且將pH值調整 至6.6-7.0,此後使組合物經過高溫短時(htst)加工,在此 期間組合物經熱處理、乳化且經均質化,謂後使其冷 卻。添加水溶性維生素及抗壞血酸,若有必要則將阳值調 整至所要範圍,添加調味劑且添加水以達成所要之總固體 含量。隨後將組合物無菌封裝形成經㈣封裝之營養乳 液。該乳液亦可經填充且隨後經殺菌,形成即食型或濃縮 型液體,5戈其可經喷霧乾#、乾混及/或聚結。 可藉由任何已知或另外適於製備及調配營養粉末之有效 技術集合來製備營養固體’諸如喷霧乾燥營養粉末或乾混 營養粉末。 舉例而言,當營養粉末為喷霧乾燥營養粉末時,喷霧乾 燥步驟可類似地包括已知或另外適用於產生營養粉末之任 何喷霧乾燥技術。已知多種不同喷霧乾燥方法及技術可用 ;吕養領$戶斤有均適用於製造本文之喷霧乾燥營養粉 末。 一種製備噴霧乾燥營養粉末之方*包含形成及均質化含 有預消化脂肪且視情況含有蛋白質、碳水化合物及其他脂 肪來源之含水漿料或液體’且隨後噴霧乾燥該蒙料或液體 以產生喷霧乾燥營養粉末()該方法可進―步包含喷霧乾 161219.doc -33- 201233342 燥、乾混或另外向喷霧乾燥營養粉末中添加其他營養成分 (包括任何一或多種本文所述成分)之步驟。 其他適用於製備營養品之方法例如描述於美國專利 6,365,218(B〇rsehei 等人)、美國專利 6 589 576(b。⑽^ 等 人)、美國專利6,306,908(Carlson等人)及美國專利申請案 20030118703 Al(Nguyen等人)中,其描述以與其一致之程 度以引用的方式併入本文中β 使用方法 根據本發明且如下文進一步描述,本文所述之營養品可 用於多種目的’例如包括改善消化、改善營養素吸收、改 善耐受性、降低壞死性小腸結腸炎之發生率、降低腹痛之 發生率及降低短腸症之發生率。使用本文所述的營養品之 個體(嬰兒、幼兒或孩童)實際上可能患有或罹患所述疾病 或病況(亦即,實際上可能具有消化、營養素吸收及/或耐 受性問題’或實際上可能患有壞死性小腸結腸炎、腹痛或 短腸症)’或可能易於患上該疾病或病況或存在此風險(亦 即’可能實際上尚未患有該疾病或病況,但由於某些條 件、家族史等與一般人群相比患病風險增加)^不管個體 實際上是否患有該疾病或病況,或是否存在患上該疾病或 病況之風險或易於患上該疾病或病況,該個體在本文中均 分類為「需要」幫助解決及對抗該疾病或病況。舉例而 言’嬰兒由於早產而實際上可能患有壞死性小腸結腸炎或 可能存在患上壞死性小腸結腸炎(易於患上壞死性小腸結 腸炎)之風險。類似地,在另一實例中’嬰兒由於患有其 161219.doc • 34· 201233342 疾病或病’兄或具有該等問題之家族史而實際上可能具有 耐又(·生及/或消化及/或營養素吸收問題,或可能存在患上 (易於患上)一或多種該等病況之風險。不管個體是否實際 上患有該疾病或病丨兄’或是否僅存在患上該疾病或病況或 易於患上該疾病或病況之風險,本發明之範疇内包括使用 本文所述之營養品協助該個體。 基於以上内容,由於本發明之某些方法實施例係關於確 定個體之特定子群或子類(亦即,「需要」幫助解決本文所 述之一或多種特定疾病或特定病況之個體的子群或子 類),因此並非所有個體均可受益於本文所述之所有方法 實施例如同對於某些疾病或病況而言,並非所有個體均 屬於如本文所述之個體子群或子類。 如本文所述之營養品包含理想地與一或多種其他脂肪來 源組合之預消化脂肪,以為嬰兒、幼兒及孩童提供營養來 源以用於改善營養素消化及吸收。特定而言,類似於母乳 餵養嬰兒之消化,因為脂肪來源在進入十二指腸之前至少 部分被消化,讓嬰兒有更多時間吸收營養素’尤其在腸 内,且進入嬰兒結腸之營養素減少,因此使得會被醱酵且 產生氣體以致降低產品耐受性之營養素減少。因此,藉由 在營養品(諸如嬰兒配方)中使用預消化脂肪來源(諸如單酸 甘油酯及/或脂肪酸),現可能向嬰兒提供更接近地模仿母 乳益處之母乳替代物或補充物。 除如上文所述之營養素吸收改善以外,已發現在營養品 161219.doc -35· 201233342 中使用預消化脂肪在與一或多種非水溶性疏水性混合物 (諸如油可溶性(脂溶性)維生素(維生素A、D、β及K)、類 胡蘿蔔素(例如葉黃素、β_胡蘿葡素、番茄紅素等)、醣脂 (神經結醣脂)、固醇及植物化學品)一起投與時亦有助於微 胞形成。該等微胞之形成使得不溶性疏水性化合物可溶解 於消化物中,此為腸絨毛吸收之步驟。此外,預消化脂肪 將用於再合成三酸甘油酯以形成乳糜微粒。乳糜微粒將非 水溶性疏水性化合物運載至淋巴中,其中循環將不溶性疏 水性化合物輸送至目標器官及/或組織以產生所要生理學 作用。 除上文論述之益處以外,已發現包含預消化脂肪之營養 品刺激十二指腸中之膽囊收縮素(CCK)產生,其刺激胰腺 脂肪酶產生。此產生導致進一步消化營養素且減少上部胃 腸道收縮’其使得有更多時間用於吸收。因此,在營養品 中使用預消化脂肪可減少進入結腸且會被醱酵並產生氣體 及發脹感受之營養素總量。因此,在營養品中使用預消化 脂肪可藉由改善營養素消化及吸收(具有較少脹氣)來改善 耐受性。此對於嬰兒可尤為重要,因為耐受性可能為某些 嬰兒中存在之問趣。 除刺激CCK產生以外,已發現預消化脂肪亦誘發腸生長 激素(胰高血糖素樣肽-2,GLP-2)之分泌。GLP-2.可增強嬰 兒腸道成熟,其使得消化及營養素吸收更佳。 已進一步發現,如本文所述之包含預消化脂肪之營養品 161219.doc -36- 201233342 可用於為嬰兒、幼兒或孩童提供營養來源,此可降低壞死 性小腸結腸炎(NEC)、腹痛及/或短腸症之發生率。 另外,在與脂肪漿料中之蛋白形成對比,藉由向碳水化 合物-礦物質漿料中添加至少一部分預消化脂肪(或在某些 實施例中為所有預消化脂肪)之方法製造營養品的實施例 中,營養品(通常為營養乳液形式)之所得穩定性可得以改 善0 實例 以下實例說明本發明營養品之特定實施例及/或特徵。 該等實例僅出於說明目的而給出且不應理解為對本發明之 限制’因為在不偏離本發明之精神及範訂可能存在其多 種變化形式。除非另外說明,否則所有例示量均為基於組 合物總重量計之重量百分比。 例不組口物為根據本文所述之製造方法製備的存放穩突 性營養品,以使得除非另外說明,否則每一例示產品均包 括經無菌加卫之實施例及經殺菌爸封裝之實施例。 營養液體實施例為封裝於24〇〇11塑膠容器中且在調配㈤ 裝之後在咖範圍内之儲存溫度下在匕以個月内維持物 理穩定性之水包油含水乳液。 實例1-4說明本發明之不含乳糖的嬰兒營養乳液,其 刀列舉於下表中°除非另外說明,否則所有成分量均以 1000公斤批次產品之公斤數列出。 161219.doc •37- 201233342 |成分 實例1 實例2 實例3 I 實例4 水 足量 足量 足量 足量 麥芽糊精 53 43.3 50 60 蔗糖 16.5 25 19.2 16.38 乳蛋白分離物 15.65 15.65 15.65 15.65 玉米油 12 12 12 12 高油酸紅花籽油 10 10 10 10 單掠摘酸甘油自旨 10 9 8 7 c1(rc24脂肪酸弼鹽 6.0 7 8 9 椰子油 2 2 2 2 真菌油 0.3 0.3 0.3 0.3 卵磷脂 0.1 0.1 0.1 0.1 磷酸氫二鉀 0.96 0.96 0.96 0.96 氣化鉀 0.3 0.3 0.3 0.3 抗壞血酸 0.235 0.235 0.235 0.235 角叉菜膠 0.150 0.150 0.150 0.150 氫氧化鉀 0.136 0.136 0.136 0.136 TM/UTM預混物 0.1684 0.1684 0.1684 0.1684 維生素A、D、E預混物 0.0758 0.0758 0.0758 0.0758 水溶性維生素預混物 0.0728 0.0728 0.0728 0.0728 蛾化鉀 0.00022 0.00022 0.00022 0.00022 氣化鉻 0.000217 0.000217 0.000217 0.000217 實例5-8 實例5-8說明本發明之基於乳糖之營養乳液,其成分列 舉於下表中。除非另外說明,否則所有成分量均以每1000 kg批次產品之kg數列出。 |成* 實例5 實例6 實例7 實例8 水 足量 足量 足量 足量 乳糖 58 66 71 63 非脂肪乾乳 25 10 0 16 乳清蛋白濃縮物 6.4 13 18 10.5 高油酸紅花籽油 14 14 14 14 161219.doc -38 - 201233342 椰子油 6.2 6.2 6.2 6.2 單棕橺酸甘油酯 10 8 6 4 C10-C24脂肪酸 5.5 7.5 9.5 11.5 果寡醣/半乳寡醣 9 9 9 9 真菌油 0.3 0.3 0.3 0.3 磷酸氫二鉀 0.96 0.96 0.96 0.96 氫氧化妈 0.78 1.07 1.36 1.64 氯化鉀 0.3 0.3 0.3 0.3 抗壞血酸 0.235 0.235 0.235 0.235 角又菜膠 0.150 0.150 0.150 0.150 氫氧化鉀. 0.136 0.136 0.136 0.136 TM/UTM預混物 0.1684 0.1684 0.1684 0.1684 維生素A、D、E預混物 0.0758 0.0758 0.0758 0.0758 水溶性維生素預混物 0.0728 0.0728 0.0728 0.0728 磁化鉀 0.00022 0.00022 0.00022 0.00022 氯化鉻 0.000217 0.000217 0.000217 0.000217 實例9-12 實例9-12說明本發明之基於大豆之嬰兒營養乳液,其成 分列舉於下表中。除非另外說明,否則所有成分量均以每 1 000公斤批次產品之公斤數列出。 成分 實例9 實例10 實例11 實例12 水 足量 足量 足量 足量 玉米糖漿固體 53 43.3 50 60 蔗糖 16.5 25 19.2 16.38 大豆蛋白分離物 19.5 19.5 19.5 19.5 玉米油 12 12 12 12 高油酸紅花籽油 10 10 10 10 單棕櫚酸甘油酉旨 10 9 8 7 Ci(pC24脂肪酸 6.0 7 8.0 9 161219.doc -39- 201233342 真菌油 0.3 0.3 0.3 0.3 L-胱胺酸 2.3 2.3 2.3 2.3 L-酪胺酸 1.1 1.1 1.1 1.1 氫氧化飼 0.09 1.0 1.1 1.2 L-色胺酸 0.66 0.66 0.66 0.66 磷酸氫二鉀 0.96 0.96 0.96 0.96 氣化鉀 0.3 0.3 0.3 0.3 抗壞灰酸 0.235 0.235 0.235 0.235 角叉菜膠 0.150 0.150 0.0 0.0 氫氧化鉀 0.136 0.136 0.136 0.136 TM/UTM預混物 0.1684 0.1684 0.1684 0.1684 維生素A、D、E預混物 0.0758 0.0758 0.0758 0.0758 水溶性維生素預混物 0.0728 0.0728 0.0728 0.0728 碘化鉀 0.00022 0.00022 0.00022 0.00022 實例13-16 實例13-16說明本發明之基於水解蛋白之嬰兒營養乳 液,其成分列舉於下表中。除非另外說明,否則所有成分 量均以每1000公斤批次產品之公斤數列出。 成分 實例13 實例14 實例15 實例16 水 足量 足量 足量 足量 蔗糖 42 42 42 42 澱粉 21.8 21.8 21.8 21.8 水解蛋白 22.2 22.2 22.2 22.2 高油酸紅花籽油 13.7 13.7 13.7 13.7 MCT油 6 6 6 6 單棕櫚酸甘油酯 10 9 8 7 Cl〇-C24脂肪酸 11 9.5 8 6.5 椰子油 5 7.5 9 11.5 真菌油 0.3 0.3 0.3 0.3 氫氧化弼 1.6 1.29 1.1 0.93 161219.doc •40· 201233342 L-蛋胺酸 0.3 0.3 0.3 0.3 磷酸氮二鉀 0.96 0.96 0.96 0.96 氣化鉀 0.3 0.3 0.3 0.3 抗壞血酸 0.235 0.235 0.235 0.235 角叉菜膠 0.0 0.0 0.150 0.150 氫氧化鉀 0.136 0.136 0.136 0.136 TM/UTM預混物 0.1684 0.1684 0.1684 0.1684 維生素A、D、E預混物 0.0758 0.0758 0.0758 0.0758 水溶性維生素預混物 0.0728 0.0728 0.0728 0.0728 峨化鉀 0.00022 0.00022 0.00022 0.00022 實例17 在該實例中,評估大鼠對C1()-C24脂肪酸鈣鹽之吸收及相 關生物可用性。 對三十隻大鼠隨機指定三種含有不同蛋白及脂肪之飲食 (飲食1、飲食2及飲食3)之一。飲食1-3與AOAC方法906.48 中所用者相同,不同之處在於飲食1-3具有較高脂肪含量 且包含麥芽糊精作為碳水化合物來源。飲食1含有1〇 wt°/〇 蛋白可用作酸酪蛋白且含有23 ·6 wt%脂肪可用作含有30 wt%椰子油、30 wt%大豆油及40 wt%高油酸紅花籽油 (HOSO)之油摻合物。飲食2及3之營養型態與飲食1之營養 型態相同,除了蛋白質、脂肪、碳水化合物及礦物質被混 合、均質化且噴霧乾燥以外。飲食3與飲食2之不同之處僅 在於以高油酸紅花籽油脂肪酸鈣鹽替代HOSO油且以磷酸 鉀替代磷酸三鈣,以使得飲食2飲食3之總體營養及礦物質 型態相同。Ca-HOSO脂肪酸鈣鹽提供100%之飲食鈣。 161219.doc • 41 · 201233342 對大鼠餵飼飲食1、飲食2或飲食3之一持續4週時期。使 用餵飼試驗結束時之飼料/蛋白攝取及體重增加來計算飼 料轉化(體重增加公克數/飼料攝取公克數)及蛋白效率比 (體重增加公克數/蛋白攝入公克數)(pER)。若由於不良吸 收,HOSO脂肪酸鈣鹽之熱量值(亦即,熱量/物質公克數) 顯著低於HOSO之熱量值,則預期飲食3之大鼠將增加較少 體重或服用更多飼料以維持其生長,其兩者均導致較低之 飼料轉化及PER。 下表中所示之結果顯示,飲食3之大鼠與對照組具有相 同之飼料轉化或PER,顯示HOSO脂肪酸鈣鹽之熱量值並 非不同於HOSO油。因此,顯示HOSO脂肪酸鈣鹽具高度生 物可用性。 蛋白效率比 飼料轉化 ~~ 飲食1(對照組1) 2.83 +/- 0.28* 0.29 +/- 0.03 飲食2(對照組2) 3.16+/-0.17 0.31 +/-0.02 飲食3(脂肪酸詞鹽) 3.32+/-0.27 0.37 +/- 0.03 *標準偏差(n=10) 實例18 在該實例中,分析10天大之豬對大豆脂肪酸鹽之吸收。 將16隻乳豬隨機分為兩組且個別地圈養於代謝籠中且經 訓練以在30分鐘内自盆中獲取營養乳液。在用市售即食型 基於水解蛋白之配方訓練一週之後,對該等豬餵飼包含磷 酸三鈣及碳酸鈣作為鈣來源之市售基於水解蛋白之配方粉 161219.doc • 42 - 201233342 末(對照組)或包含大豆脂肪酸鈣鹽作為鈣來源之乳液(實驗 乳液)。對於對照組及實驗乳液而言,蛋白質來源及含 量、脂肪含量及礦物質型態相同。然而,實驗乳液包含大 豆脂肪酸替代對照組中之大豆油,且包含氫氧化鈣作為鈣 礦物質系統之一部分以中和大豆脂肪酸。調整實驗乳液之 磷酸鉀含量以與對照組之磷含量相匹配。大豆脂肪酸鈣提 供實驗乳液中1 00%之鈣。 在餵飼兩週之後,基於下式計算表觀脂肪及鈣消化率: 表觀脂肪消化率=((脂肪攝取-糞便脂肪)/脂肪攝取)* i00 表觀弼消化率=((弼攝取-糞便弼)/舞攝取)* i 〇〇 乾物質消化率=((乾物質攝取-糞便乾物質)/乾物質攝 取)*100 實驗乳液減少之飼料轉化(重量/飼料攝取)及減少之脂 肪、鈣及乾物質消化率將顯示實驗乳液之大豆脂肪酸鈣鹽 吸收不良,且因此顯示對於實驗乳液而言,鈣之熱量值及 生物可用性低於對照組。 如下表中所示,實驗乳液之飼料轉化、脂肪消化率及乾 物質消化率顯著不同於對照組,顯示對於初生豬而言,實 驗乳液之大豆脂肪酸鈣鹽被高度吸收且具生物可用性。此 外,下文所示之表觀鈣消化率資料顯示實驗乳液之大豆脂 肪酸鈣鹽比對照組中包含之鈣(亦即’磷酸三鈣及碳酸鈣) 更具生物可用性。 161219.doc -43- 201233342 表觀脂肪 消化率 飼料轉化 (體重增加 公克數/飼料 (乾物質)公克數) 表觀鈣 消化率 表觀乾物質 消化率 對照組 97.6+/- 1.0 0.82 +/- 0.14* 81.8+/-7.2 97.8 +/- 0.7 實驗乳液 97.6+/- 1.4 0.80+/-0.15 91.3+/-3.3 98.0+/-1.0 *標準偏差(n=10) 實例19 在該實例中,分析脂肪酸鈣鹽之乳化特性。 藉由使用桌上型高剪切混合器用500 ml水剪切丨8 g 130°F含有單棕櫊酸甘油酯(油之5重量%)之大豆油及43〇 mg Ca(磷酸三鈣形式)來製備第一乳液(對照乳液)。作為對 照乳液的含有相同含量之鈣及脂肪(12 g大豆油加上6 g大 豆脂肪酸)之第二乳液(脂肪酸鈣乳液)係藉由以下來製備: (1) 在約130°F之溫度下將大豆脂肪酸油溶液分散於水中; (2) 添加430 mg氣化鈣形式之Ca ; (3)使用KOH將溶液PH值 調整至約7.0 ;及(4)使用桌上型高剪切混合物剪切混合 物。 使對照乳液及脂肪酸鈣乳液靜置三週時期以分析乳液分 離。在經過一夜之後,對照乳液在乳液頂部出現包含乳狀 層之可見相分離。(參見圖1A)。相比而言,儲存三週之 後,脂肪酸弼乳液在乳液頂部僅出現輕微可偵測(但並非 清楚可見)之弼皂層’而乳液仍保持一相。在脂肪酸弼乳 液底部無可見之鈣沈降(參見圖1B)。 該等結果顯示脂肪酸釣鹽為有效乳化劑且能夠為實質上 161219.doc -44 - 201233342 不會自溶液沈降之營養乳液提供鈣來源。此使得乳液產品 具有改善之穩定性及較長之存放期。 實例20 在該實例中,量測1 〇天大豬對兩種獨立測試調配物及對 照調配物之脂肪吸收量及鈣吸收量。 第一測試調配物(調配物1)在脂肪系統中包含棕櫊油精 油’第二測試調配物(調配物2)在脂肪系統中包含預消化脂 肪’且對照調配物(調配物3)在脂肪系統中包含低標棚酸 油。三種調配物之脂肪系統組分列舉於下表中。 營養素(公克) 調配物1 (棕橺油精油 调配物) 調配物2 (預消化脂肪 調配物) 調配物3 (包含低棕櫚酸油 之對照調配物) 椰子油 37.2 0 84.1 尚油酸紅花軒油 62.8 108 111.9 大豆脂肪酸 0 56.9 0 ARA油 3.03 3.03 3,03 DHA油 1.52 1.52 1.52 單棕櫊酸甘油酯 0 65.4 0 卵磷脂 1.12 1.12 1.12 棕櫊油精 122.7 0 0 大豆油 57.1 0 83.8 製備三種具有幾乎相同的營養素及礦物質型態之調配 物。調配物1及2之脂肪酸型態模仿母乳脂肪酸型態。調配 物2中包含氫氧化鈣(足以螯合所有游離脂肪酸之量)作為鈣 來源,其與大豆脂肪酸反應以形成不溶性脂肪酸鈣鹽。該 反應消除游離脂肪酸所產生之苦味及咽喉燒灼感受。另 161219.doc • 45 - 201233342 外,升高調配物2中磷酸鉀之含量以與調配物1及3中之磷 含量相匹配。調配物1及3中所用之鈣鹽為磷酸鈣。 使60隻1〇天大豬(加或減兩天)隨機分組接受調配物1、 調配物2或調配物3。使豬個別地圈養於代謝籠中且在訓練 及適應4天之後每天餵飼五次持續三週。收集第2天至第ι8 天之糞便物質且分析鈣吸收及脂肪吸收。以糞便物質+之 鈣量除以飲食令之鈣量再乘以100計算鈣吸收。以糞便物 質中之脂肪量除以飲食中之脂肪量再乘以1〇〇計算脂肪吸 收。結果展示於下表中。 脂肪吸收(%) 鈣吸收 調配物1(棕櫚油精) 92.3 ±3.9 88.9 士 4.7 調配物2(預消化脂肪) 98.2 ± 0.7 93.1 ±2.4 調配物3(對照:低棕 櫊酸脂肪系統) 98.0 ± 1.4 90.7 ±3.5 如上表中之結果所顯示,使用預消化脂肪系統使得嬰兒 配方可模仿母乳脂肪酸型態不會出現如使用棕櫚油精油脂 肪系統時所經歷對鈣及脂肪吸收之不利影響。配方2(預消 化月s肪調配物)之脂肪及弼吸收速率至少與低棕摘酸配方 之月曰肪及約吸收速率同等良好。該等發現說明大豆脂肪酸 鈣鹽在初生豬中具高度生物可用性。 實例21 在該實例中,評估實例20之豬的CCK產生(AUC)及腸動 素產生(AUC)之餐後增加量。 在實例20中所述之脂肪及鈣吸收分析之結論中,使經投 161219.doc -46 - 201233342 與調配物2(預消化脂肪調配物)或調配物3(包括低棕櫚酸之 對照調配物)之豬禁食1 2小時,且抽取禁食血液以分離血 清。使豬恢復兩小時且隨後給予250 mL調配物2或調配物 3。在餵飼後30及6〇分鐘時抽取餐後血液樣本且測試CCK 及腸動素《計算CCK(曲線下面積)及腸動素(AUC)之餐後 增加量。結果展示於下表中。 調配物2 (預消化脂肪調配物) (pg/mL*min) 調配物3 (對照:低棕櫚酸調配物) (pg/mL*min) CCK分泌之餐後增加 量(曲線下面積) 1935 ±1464 1046 ±754 腸動素AUC(餐後增 加量) 483±253 839±403 上表中之資料顯示以預消化脂肪(單棕櫚酸甘油酯加大 豆脂肪酸)替代三酸甘油酯會刺激餐後CCK分泌’其已顯 示刺激胰腺消化酶分泌、增強膽囊收縮且延遲口腔至盲腸 之輸送》因此,具有預消化脂肪之調配物可刺激更多可消 化酶分泌且減緩GI輸送以允許更多營養素消化及吸收。因 此,包含預消化脂肪之調配物可改善配方耐受性’因為未 消化之營養素可導致過度結腸醱酵而導致脹氣、腹瀉及胃 脹。 另外,上表中之資料顯示以預消化脂肪(單椋櫊酸甘油 酯加大豆脂肪酸)替代三酸甘油酯可減少餐後腸動素分 泌。已顯示,患腹痛之嬰兒具有較低之餐後CCK含量,但 具有較高之餐後腸動素含量。餐後腸道激素之間的此種不 161219.doc -47- 201233342 平衡導致嬰兒GI收縮’其導致腹痛。上表中之資料顯示包 含預消化脂肪可增加嬰兒之餐後CCK含量,但減少腸動素 含量,由此減小激素不平衡以緩解GI收縮、腹痛及腹痛。 實例22 在該實例中,使用實例20之豬來研究各種脂肪系統對乳 糜微粒三酸甘油酯棕棚酸及Sn-2標棚酸含量之影響。 自每隻豬抽取1小時餐後血液樣本且分離血漿,以液氮 冷冻·且储存在-80°C之冷凍器中。使用Folch溶劑萃取總血 漿脂質。藉由薄層層析分離三酸甘油酯。下表顯示調配物 1(棕櫊油精調配物)及調配物2(預消化脂肪調配物)之血漿 三酸甘油酯棕櫊酸及Sn-2棕櫚酸。表中亦展示餵飼該兩種 調配物之豬的乳糜微粒三酸甘油酯及Sn-2棕櫊酸。 調配物1 : (棕撊油精) 银飼調配物1 之諸的血漿三 酸甘油酯 調配物2 : (預消化脂肪) 餵飼調配物2 之豬的血漿三 酸甘油酿 飯飼母乳之人 類嬰兒的血漿 三酸甘油酯 三酸 甘油醋 Sn-2 三酸 甘油醋 Sn-2 三酸 甘油酯 Sn-2 三酸 甘油酯 Sn-2 三酸 甘油酯 Sn-2 棕櫊 酸含 量(%) 23.3 5.8 18.3 10.6 21.4 5.2 18.5 14.4 25 25.5 如上表中所示,餵飼預消化脂肪配方之豬的血漿三酸甘 油酯及Sn-2棕櫚酸含量顯著高於餵飼棕櫚油精配方之豬。 調配物1及調配物2之血漿三酸甘油酯棕橺酸/Sn-2棕橺酸比 率分別為約1.7及1.3,且已知母乳餵飼嬰兒之該比率為約 1.1。因此,該資料顯示預消化脂肪調配物比棕櫊油精脂 肪調配物能更佳地模仿母乳。 161219.doc •48- 201233342 實例23 在該實例中,使用實例2G之豬來研究各種脂肪系統對血 液葉黃素含量之影響。 使用氣仿與甲醇之溶劑(比率為2:1)萃取來自每隻豬之i 小時餐後血液樣本的血漿,移除溶劑且彙集所得脂質且使 用%知方法分析葉黃素。下表展示餵飼調配物丨(棕櫚油精 調配物)、調配物2(預消化脂肪調配物)及調配物3(低棕櫚 酸調配物)之豬的葉黃素含量,以每mg脂質之葉黃素㈣數 表示。 調配物1 : (棕櫊油精) 調配物2 : (預消化脂肪) 調配物3 : (低棕櫚酸) 葉黃素含量 N/A* 0.765 pg 0.539 pg *調配物1之葉黃素含量過低而難以量測。 如上表中所示’餵飼包含預消化脂肪之調配物之豬與银 飼包含棕櫚油精或低棕櫊酸之調配物之豬相比具有増加之 葉黃素吸收。 實例24 在該實例中,使用實例20之調配物.2(預消化脂肪調配 物)及調配物3(低棕櫚酸調配物)來研究各種脂肪系統對微 胞葉黃素含量之影響。 使調配物2及調配物3用水復原(每1.0 L水133 g粉末狀調 配物)’且添加HC1將復原調配物之pH值調整至4.5。藉由 向40 ml復原調配物中添加i_〇〇 ml USP胃蛋白酶(56 mg/mi) 使復原調配物在室溫下消化1小時*在胃蛋白酶消化之後 161219.doc -49- 201233342 將復原調配物之pH值調整至7.0,且隨後向經胃蛋白酶消 化之調配物中添加28 mg USP胰澱粉酶/蛋白酶、28 mg USP胰酶脂肪酶與1 08 mg膽汁萃取物之混合物。使調配物 在室溫下進一步消化2小時且離心(31,000 g,在20eC下,3 小時)。經消化之調配物形成油/乳脂凝塊、含水相及沈降 層。抽取含水相以用於微胞之葉黃素分析,該等微胞在含 水内腔中吸收葉黃素期間充當載體。下表展示每kg消化調 配物之微胞葉黃素的含量。 消化調配物2 : (預消化脂肪) 消化調配物3 : (低棕櫚酸) 微胞葉黃素(pg) 0.598 pg 0.246 μξ 如上表中所示,在包含預消化脂肪之消化調配物中發現 之微胞葉黃素的量為在包含低棕搁酸之消化調配物中發現 的微胞葉黃素之量的兩倍多’由此顯示使用預消化脂肪可 增加葉黃素吸收。 實例25 在該實例中,分析預消化脂肪降低軟便發生率之能力。 對30隻斷乳大鼠餵飼基於水解蛋白之粉末嬰兒配方(包 含MCT油作為3〇 wt%之脂肪來源),持續四天適應期。在 適應期、纟。束時,將大鼠隨機分為兩組且餵飼對照調配物 (低標櫚酸私末嬰兒配方)或測試調配物(含有預消化脂肪之 嬰兒配方)^對照調配物與測試調配物之營養素型態相 同。使大鼠可自由獲取飼料及水達五天,且每天記錄攝入 之飼料量及體重。 161219.doc 201233342 儘管兩組之間的飼料攝取或體重增加無顯著差異,但大 便堅實度存在顯著差異。在餵飼之最後兩天期間,使用〇_ 5點系統對大鼠之大便堅實度評分°評分係基於黏結至寵 底吸取薄片之大便的嚴重度及堅實度。0評分值指示正常 . 大便且5評分值指示水樣腹瀉。如圖2中所示,傲飼對明調 . 配物(含有MCT油)之大鼠比餵飼測試調配物(含有預消化脂 肪)之大鼠產生較稀之大便。 實例26 在該實例中’分析預消化脂肪降低壞死性小腸結腸炎 (NEC)發生率之能力。 將經由剖腹產分娩之早產豬(92%孕期)即刻轉移至充氧 培育器(37°C )中且在臍動脈中置放一血管導管。在第一個 24小時期間經由血管導管對該等豬注射三次(4、6及7 mL/kg體重)母體血漿。以每小時4_6 mL/kg之速率提供完 全胃腸外營養(Total parenteral nutrition,TPN)持續 24 小 時。隨後使該等豬經由口胃管(or〇gastric tube)以每小時5 mL/kg之速率隨機分組接受對照調配物或pdf調配物。除 其中之脂肪系統以外,對照調配物與pDF調配物相同。特 .疋而s,對照調配物中之脂肪系統包含植物油,且pDF調 配物中之脂肪系統包含3〇 wt%單棕櫚酸甘油酯' 2〇 wt%大 丑月曰肪酸、26 wt°/。高油酸紅花籽油、丨4 wt%椰子油及1 〇 wt0/。甘油二丁酸酯^對照調配物與pDF調配物兩者每公升 調配物_均包含100 g蛋白質、47 g脂肪及50 g玉米糖漿。 在經腸傲飼36小時之後使該等豬安樂死且進行屍檢以使用 161219.doc 201233342 1-5評分系統評估NEC病變之嚴重程度,其中1評分值指示 無NEC跡象。結果展示於下表中。 區塊1 區塊2 對照 PDF 對照 PDF 調配物 調配物 調配物 調配物 (n=5) (n=3) (n=5) (n=3) 早期NEC死亡 2 0 3 1 屍檢時彳貞測之NEC 2 1 0 0 總NEC 4 1 3 1 如上表中所示,餵飼對照調配物之1 0隻豬中有5隻(50%) 在腸餵飼期結束之前即死於NEC,但餵飼PDF調配物之6隻 豬中僅有1隻(16.7%)在腸餵飼期結束之前死於NEC。另 外,餵飼對照調配物之10隻豬中有7隻(70%)在腸餵飼期結 束之前經測定即患有NEC,而餵飼PDF調配物之6隻豬中僅 有2隻(33%)在腸餵飼期結束之前經測定患有NEC。因此可 得出結論,藉由以包含預消化脂肪之脂肪系統替代植物油 脂肪系統可降低NEC之發生率。 【圖式簡單說明】 圖1A及圖1B展示如實例19中製備之對照乳液及實驗乳 液的圖示。 圖2為展示飲食對糞便堅實度之影響的圖。 161219.doc -52-The Cio C24 fatty acid source can be mixed with the calcium source for at least 1 minute. Mixing can also be performed at least 5, 15, 2, 25, 3, 35 4, 45, 5, 55, 60, 65, 7, 75, 8, 8, 9, % or ι Minutes, any of which may form an upper or lower end if appropriate. Mixing can be carried out at various temperatures, but the method is generally performed at high temperatures 161219. Doc 201233342 Health. The exact elevated temperature may depend on C1 (a particular starting source of rC24 fatty acid or calcium and its amount. Suitable temperatures at which the disclosed mixing can be carried out include, but are not limited to, from about 4 ° C to about 100 ° c, from about to about 100 ° C, about 15 ° C to about 100 ° C, or about 20 ° C to about 70 ° C. Containing C 〇 -C24 fatty acid or calcium source can also be heated before mixing. This preheating step can be Performed at any temperature or temperature range as described herein. In certain embodiments, the mixing of 'C 10-(:24 fatty acid and calcium) can be carried out under reduced pressure. Suitable pressure is less than or equal to about 1 Torr or Less than or equal to about 0. 1 Torr. In a preferred embodiment, the C1()-C24 fatty acid calcium salt is obtained by adding free C1()-C24 unsaturated fatty acid and a calcium source such as Ca(otl)2, CaCl2, CaC〇3, calcium citrate or A mixture of equal salts) is prepared to form an oil blend. More specifically, the fatty acid is dissolved in a warm aqueous solution (e.g., having a temperature of from about 40 ° C to about 80 ° C). The pH of the solution can be adjusted to a pH of typically about KOH using KOH or NaOH. Calcium is then added to the dissolved fatty acid-containing solution. The fatty acid and calcium are typically allowed to stand for 1 minute to ensure complete reaction between the fatty acid and the calcium ion. The mixture is then homogenized to form an oil exchange compound. In another preferred embodiment, a mixture of fatty acid calcium salts (including fatty acids from fish oil, algae oil, fungal oil, and soybean oil) is prepared as part of the pre-digested fat system. Fish oil, algae oil, fungal oil and soybean oil are mixed together and hydrolyzed by potassium hydroxide under a nitrogen blanket. A calcium source (such as calcium carbonate) is then added to the mixture to react with the fatty acid to produce 161,219. Doc -20- 201233342 Raw insoluble fatty acid calcium salt. These insoluble fatty acid salts can be separated by a transition and washed with water, followed by vacuum drying. It has been surprisingly found that although fatty acid salts (such as fatty acid calcium salts) are generally insoluble in nutrients', they do not settle in solution to form a sediment layer that is difficult to redisperse. Thus, the use of fatty acid calcium salts and/or fatty acid salts allows for better calcium/magnesium delivery' and in various embodiments eliminates the need for other stabilizers, such as horns and vegetables, so that the product can be substantially or Completely "no angle and vegetable glue". Thus, the use of fatty acid salts improves the bioavailability of calcium and/or magnesium and fatty acids compared to products that use calcium phosphate or calcium carbonate as the source of calcium. Furthermore, it has been found that the use of fatty acid salts in the nutritional products of the present invention provides bioavailable fatty acids such as arachidonic acid (ARA) and analogs thereof, which are shown to enhance infant growth. The use of pre-digested fat also provides a milky nutritional supplement with improved product stability and long shelf life. The nutritional product typically comprises at least about 10% by weight of the fatty acid or fatty acid salt, based on the fat component contained in the nutritional product, including at least about 5% by weight based on the fat component contained in the nutritional product. /. Including at least about 2 〇 weight / 〇, including about 10 weight. /. Up to about 60 weight. /. And including from about 15% by weight to about 40% by weight, and including from about 15% by weight to about 35% by weight, including about 1% by weight, including about 15% by weight. /〇, comprising about 20% by weight, including about 25 weights/0, including about 30% by weight, including about 35 weights/〇 and further including about 40% by weight, or even about 50% by weight, or even about 60% by weight. %, or even about 7% by weight, or even about 80% by weight, or even about 90% by weight, or even 161219. Doc •21 - 201233342 About 100% by weight. In certain embodiments, the nutritional product comprises a mixture of a fatty acid component and a monoglyceride containing a fatty acid. In such embodiments, the nutrient comprises a mixture of at least i 0% by weight of the fat component contained in the nutritional product, comprising at least about i 5 weight based on the fat component contained in the nutritional product. %, includes at least about 20% by weight, including from about 8% by weight to about 40% by weight, including from about 20% by weight to about 65% by weight. /. And including from about 25% by weight to about 50% by weight, including from about 15% by weight to about 3% by weight, and including from about 15% by weight to about 25% by weight, including about 1% by weight, including about 5% by weight, Includes about 20 weights /. Including about 25 weights ❶ /. Including about 3% by weight, including about 5% by weight, and further comprising about 4,000% by weight or even about 50% by weight, or even about 60% by weight, or even about 7% by weight, or even about 8 〇. % by weight, or even about 90% by weight or even about 〇〇 weight 〇/〇. In other embodiments, the nutritional product comprises at least 0% of the total dry matter in the nutritional product. 2% by weight, including at least 1% by weight, including at least 2% by weight and including at least 5% by weight of fatty acid component, fatty acid-containing monoglyceride Ester or a combination thereof. Macronutrient Although the total concentration or amount of fat, protein and carbohydrate can be determined by product type (ie, human milk fortifier, infant formula, etc.), product form (ie, nutritive solids, powder, ready-to-feed liquid or concentrated) The type of liquid) and the intended dietary requirements of the intended user vary, but such concentrations or amounts most generally include any other fat, protein and/or carbohydrate component as described herein in the specific range H below. 1612I9. Doc -22- 201233342 For liquid preterm and term infant formulas, the carbohydrate concentration is generally from about 5% to about 40%, including from about 7% to about 30%, by weight of the preterm or term infant formula. Including from about 1〇〇/0 to about 25%; the fat concentration (including pre-digested fat and any other fat source) is most generally about 1 based on the weight of the preterm or term infant formula. /❶ to about 30〇/〇, including about 2°/. Up to approximately 5% and include approximately 30/. To the extent of about 10%; and the weight of the preterm or term infant formula, the protein concentration is most generally about 〇. 5〇/0 to about 30. /. Including from about 1% to about 15°/. And includes from about 2% to about 10%. For liquid human milk fortifier products, the carbohydrate concentration is generally from about 1% to about 75%, including from about 10% to about 50%, including from about 20% to about 40% by weight of the human milk fortifier. Within the range of %; the fat concentration (including pre-digested fat and any other fat source) is generally from about 10°/〇 to about 40°/weight, based on the weight of the human milk fortifier. Including from about 5% to about 37°/. And including from about 18.8% to about 30%; and the protein concentration is most generally from about 5% to about 40%, including from about 1% to about 30%, and including about 15% by weight of the human milk fortifier. % to about 25%. In addition to or as an alternative to the percentage of total calories in the nutritional products listed in the following table, the amount or amount of carbohydrate, fat and/or protein in the liquid nutritional product is also characterized. The macronutrients used in the liquid nutritional products of the present invention are most generally formulated in any of the calories described in the following table (Examples A-F) (the term "about" is used before each value). 161219. Doc -23- 201233342 Total nutrient calories % Example A Example B Example C Carbohydrate 0-98 2-96 10-75 Protein 0-98 2-96 5-70 Fat 0-98 2-96 20-85 Implementation Example D Example E Example F Hydrophobic compound 30-50 25-50 25-50 Protein 15-35 10-30 5-30 Fat 35-55 1-20 2-20 In a specific example, a liquid infant formula ( Instant noodles and concentrated liquids include those examples in which the protein component may constitute from about 7.5% to about 25% of the caloric content of the formulation; the carbohydrate component may comprise from about 35% to about 50% of the infant formula. The total caloric content; and the fat component can comprise from about 30% to about 60% of the total caloric content of the infant formula. These ranges are provided by way of example only and are not intended to be limiting. Other suitable ranges are listed in the table below (each term has the term "about"). Total nutrient calories % Example G Example 碳水化合物 Carbohydrate: 20-85 30-60 35-55 Fat = 5-70 20-60 25-50 Protein: 2-75 5-50 7-40 When Nutrition In the case of a powdered preterm or term infant formula, the protein component is from about 5% to about 35%, including from about 8% to about 12%, and includes from about 10% to about 12, by weight of the preterm or term infant formula. The amount of % is present; the fat component is present in an amount from about 10% to about 35%, including from about 25% to about 30%, and including from about 26% to about 28%, by weight of the preterm or term infant formula; The carbohydrate component is from about 30% to about 161,219 by weight of the preterm or term infant formula. Doc -24- 201233342 85/. Including about 45% to about 60. /. And it includes about 5% to about 55%. For powdered human milk fortifiers, the protein component is from about 1% to about 55% by weight of the human milk fortifier, including from about 1% to about 5% by weight and including about 10%. Up to about 30 / 存在 in an amount of from about 1% to about 30%, including from about 1% to about 25%, and including from about 1% to about 20% by weight of the human milk fortifier The carbohydrate component is present in an amount of from about 15% to about 75%, including from about 15% to about 6%, and including from about 2% to about 50% by weight of the human milk fortifier. The amount exists. The total amount or concentration of fats, carbohydrates, and proteins in the powdered nutritional products of the present invention can vary to a considerable extent depending on the selected product and the intended user's dietary or medical needs. Other suitable examples of macronutrient concentrations are listed below. In this context, total or concentration refers to all sources of fat, carbohydrate and protein in a powdered product. For powdered nutritional supplements, these totals or concentrations are most generally and preferably formulated within any of the specific ranges set forth in the table below (all values have "about" before). Total nutrient calories % Example J i Example K Carbohydrate 1-85 30-60 35-55 Fat 5-70 20-60 25-50~~ Protein 2-75 5-50 7-40 Fat in addition to pre-digested fat The nutritional product of the present invention may also comprise other sources of fat (the total amount of fat referred to herein as the "fat component" or "fat system" of the nutritional product). Other fat sources suitable for use in this article include those suitable for 161219. Doc -25 201233342 Any fat or fat source that is used in oral nutrition and is compatible with the elements and characteristics of these products. Non-limiting examples of other fats or sources thereof for use in the nutritional products described herein include coconut oil, fractionated coconut oil, soybean oil, corn oil, olive oil, safflower oil, high oleic safflower oil, oleic acid. (EMERS〇I^ 6313 oleic acid), MCT oil (medium chain triglyceride), hollyhock oil, high oleic sunflower oil, palm oil and palm kernel oil, palm olein, canola oil, Aquatic animal oil, fish oil, fungal oil, algae oil, cottonseed oil and combinations thereof. In one embodiment, a suitable fat or source thereof comprises an oil and oil blend comprising a long chain polyunsaturated fatty acid (LC-PUFA 'preferably LC-PUFA having four or more double bonds) . For example, certain non-limiting specific polyunsaturated acids that may be included include docosahexaenoic acid (DHA), arachidonic acid (ARA), eicosanoic acid (epa), and the like. . The pre-digested fats described herein are typically included in the nutritional product in combination with one, two, three, four or more other fat sources. In one embodiment, a monoglyceride (ideally in the form of a monopalmitate), a fatty acid (ideally in the form of a calcium salt), a high oleic acid oil, and a coconut oil are combined to provide a nutritional product. Fat component. In this embodiment, the 'monoglyceride is from about 1% to about 4% by weight based on the weight of the monthly fat component (including about 100/ to about 30%, including about 10%, about i5y, about 2). 〇%, about 23〇/. and about 25%) are present; the fatty acid is from about i% to about 40% by weight of the fat component (including about 1% to about 3%, including about 1〇0/., about 15%, about 2〇〇/0 and about 25%) is present; the high oleic acid oil is from about 1% to about 40% by weight of the fat component (including about 1 〇) % to about 3〇%, including about 丨〇%, about 〇5〇/〇, 161219. Doc -26· 201233342 About 20°/. , about 25% and about 30%); and from about 1% to about 40% by weight of the fat component, including from about 10% to about 30%, including about 10%, about 15% , about 17 ° /., about 20% and about 25%). In another embodiment, a fatty acid containing monoglyceride (ideally in the form of monopalmitate), a fatty acid component (ideally in the form of a calcium salt), high oleic safflower oil, and coconut oil Combined to provide a fat component in the nutritional product. In this embodiment, the monoglyceride is from about 1% to about 40% by weight of the fat component. (including from about 1% to about 3%, including about 10%, about 15%, about 20%, about 23%, and about 25%); the fatty acid is about 1% by weight of the fat component Up to about 4% by weight (including about 1% to about 30%, including about 10%, about 15%, about 20%, and about 25%); based on the weight of the fat component, 'high oleic acid oil From about 1% to about 4% by weight (including about 1% to about 30%, including about 10%, about 15%, about 20%, about 25%, and about 30%); The coconut oil is present in an amount from about 1% to about 40%, including from about 10% to about 30%, including about 10%, about 15%, about 17%, about 20%, and about 25% by weight. In another embodiment, a fatty acid containing monoglyceride (ideally in the form of monopalmitate), a fatty acid component (ideally in the form of a salt), high oleic safflower oil, coconut oil The DHA-containing oil and the ARA-containing oil are combined to provide a fat component in the nutritional product. In this embodiment, the monoglyceride is from about 1% to about 40% by weight of the fat component, including from about 10% to about 30%, including about 10%, about 15%, about 20%, about 23[deg.]/〇 and about 25%) are present; the fatty acid is from about 1 〇/〇 to about 40% by weight of the fat component (including about 10% to about 30%, including about 10%, about 15%). About 161219. Doc . 27·201233342 20% and about 25%) are present; from about 1% to about 40% by weight of the fat component, including from about 1% to about 30%, including about 1% , about 15%, about 20%, about 25%, and about 30%); and the coconut oil is from about 1% to about 40% by weight of the fat component (including about 1% to about 3%) %, including about 10%, about 15%, about 17.7%, about 20%, and about 25%) is present. The DHA-containing oil is present in an amount of from about 1% to about 1% by weight (including about 5%) by weight of the fat component and from about 1% to about 1% by weight of the ARA oil by weight of the fat component ( Including about 5%). In another embodiment, the fat component comprises about 38% by weight high oleic safflower seed oil, about 1 7% by weight coconut oil, and about 23% by weight single palmitic acid. Glyceryl ester, about 20% by weight of fatty acid calcium salt, about 〇. 5°/. (by weight) containing DHA oil and about 1. 0. /. (by weight) containing ARA oil. Protein In addition to pre-digested fat, the nutritional product of the present invention may further comprise a protein as appropriate. Any protein source suitable for oral nutrition and compatible with the elements and characteristics of such products is suitable for use in combination with predigested fat. Non-limiting examples of proteins or sources thereof suitable for use in such nutritional products include hydrolyzed, partially hydrolyzed or non-hydrolyzed protein or protein sources, which may be derived from any known or otherwise suitable source, such as a dairy (eg, cheese) Protein, whey) 'Animal (eg meat, fish), booty (eg rice, corn), plants (eg soybean) or a combination thereof. Non-limiting examples of such proteins include milk protein isolates, milk protein concentrates as described herein, casein: excipients, extensively hydrolyzed pathway proteins, whey proteins, passin sodium salts or word salts, Whole milk, partially or completely skimmed milk, soy protein isolate, soybean 161219. Doc • 28 - 201233342 Protein concentrates and more. Carbohydrates The nutritional products of the present invention may further comprise, as appropriate, any carbohydrates suitable for use in mouth, serving nutrients and compatible with the elements and characteristics of such products, which are suitable for use in the carbohydrates described herein. Illustrative examples of sources may include maltodextrin, hydrolyzed or modified powder or jade; powder, glucose polymer, corn syrup, corn syrup solids, M-calculated carbohydrates from rice, carbohydrates derived from peas , from Ma Yu, 7 Department of carbohydrates, cassava, sucrose, glucose, fructose, lactose, high fructose rice syrup, honey, sugar alcohol (such as maltitol, erythritol, sorbitol = alcohol), artificial sweetener (eg, sucralose, potassium citrate, stevia) and combinations thereof. Other Ingredients Dependent on the Conditions The nutritional products of the present invention may further comprise other components as appropriate, which may alter the physical, chemical, aesthetic or processing characteristics of the products, 1 acting as a pharmaceutical or other when used in the target population. Nutritional components. A variety of such components are known to be present or otherwise suitable for use in a medical food or pharmaceutical dosage form and can also be used in compositions herein. 2: The components present in such conditions are orally safe and can be selected from selected products. The ingredients of the form are compatible. Non-limiting examples of such optional ingredients include preservatives, antioxidants, emulsifiers, buffers, fruit sugars, galactooligosaccharides, probiotics, pharmaceutically actives, other nutrients as described herein. , colorants, flavoring agents, thickeners and stabilizers, emulsifiers, lubricants, and the like. I61219. Doc • 29· 201233342 The nutritional product may further comprise a sweetener, preferably comprising at least one sugar alcohol, such as maltitol, erythritol, sorbitol, xylitol, mannitol, isomalt ( Isolmalt) and lactitol, and preferably also includes at least one artificial or high-potency sweetener such as acesulfame K, aspartame, sucralose, saccharin, stevia and tagatose Se). Such sweeteners, especially in combination with sugar alcohols and artificial sweeteners, are particularly suitable for formulating liquid beverage embodiments of the present invention having a desired taste profile. These sweetener combinations are particularly effective for masking undesirable tastes sometimes associated with vegetable proteins added to liquid beverages. The sugar alcoholity of the nutrient as the case may be at least 0. 01°/. , including from 01% to about, and also including from about 1 ° / 〇 to about 6%. The artificial sweetener concentration, as the case may be, may be in the weight of the nutritional product. 〇1. /❶, including approximately 〇5% to approximately 5%, including approximately 0. 1% to about 1. Within 0% range. A flow or anti-caking agent can be included in the nutrient as described herein to delay the agglomeration or agglomeration of the powder over time and to produce a powder embodiment that readily flows out of its container. Any known flow or anti-caking agent known or otherwise suitable for use in nutritional powders or product forms is suitable herein, non-limiting examples of which include tricalcium phosphate, citrate, and combinations thereof. The concentration of the flow agent or anti-caking agent in the nutritional product varies depending on the product form, other selected ingredients, desired flow characteristics, etc., but is most often from about 01% to about 4% by weight of the nutritional product, including about 0. . 5% to about 2%. Stabilizers can also be included in the nutritional product. Known or otherwise suitable for nutrition. Any of the stabilizers herein are also suitable for use herein by some of the non-limiting examples of carrageenan and gums (such as Sanxian gum). Based on the amount of nutrients ^ 〇α $, steady I61219. Doc •30- 201233342 The dosage can account for about 0. 1% to about 5. 0%, including about 5% to about 3%, including about 0. 7% to about 1. 5%. The nutritional composition may further comprise any of a variety of other vitamins or related nutrients, non-limiting examples of which include vitamin A, vitamin D, vitamin E, vitamin K, thiamine, riboflavin, pyridoxine, vitamin 812, Molin (eg, beta-carotenoid, zeaxanthin, lutein, lycopene), niacin, folic acid, pantothenic acid, biotin, vitamin C, choline, inositol, its salts and derivatives, and Its combination. The nutrient may further comprise any of a variety of other minerals, non-limiting examples of which include calcium, phosphorus, magnesium, iron, zinc, manganese, copper, sodium, potassium, molybdenum, chromium, gas ions, and combinations thereof. Moreover, in certain embodiments, the nutritional product may be free of horn and vegetable gum. Method of Manufacture The nutritional products of the present invention can be prepared by any of the manufacturing techniques known or otherwise effective to prepare the solid or liquid form of the selected product. A variety of such techniques are known to be useful in any given form of product, such as a nutritional liquid or powder, and are readily applied to the nutrients described herein by those of ordinary skill in the art. Thus, the nutritional product of the present invention can be prepared by any of various known or otherwise effective products or methods of manufacture. For example, at least three types of slurry, including a fat-package protein (piF) slurry, a carbohydrate-mineral (CHO-MIN) slurry, and a water-packed protein (PIW) slurry, are separately prepared in a suitable manufacturing process. ^ pif slurry by heating and mixing oils (such as monoglyceride and / or fatty acids, fatty acid-containing oil, canola oil, corn oil 161219. Doc 31 - 201233342, etc.) and then formed by the addition of an emulsifier (for example, aquilin), a fat-soluble vitamin, and a part of total protein (for example, milk protein concentrate, etc.) with continuous heating and stirring. The CHO-ΜΙΝ slurry is formed by adding the following substances to the water with heating: minerals (eg, citric acid unloading, carbonic acid, sodium citrate, etc.), traces and ultra-trace minerals (TM/ UTM premix) and/or thickeners or suspending agents (eg, avicel, gellan, carrageenan). The obtained CHO-MIN slurry is kept under continuous heating and stirring for 10 minutes, and then other minerals (such as gasification _, carbonic acid, moth clock, etc.) and/or carbohydrates (for example, oligobiliary, vegetable sugar) , corn syrup, etc.). Then, if there is any remaining protein, the PIW slurry is formed by mixing with heating and stirring. In a particular embodiment of the invention 'all or a portion of the pre-digested fat contained in the nutritional product may be added to the CHO-MIN rong, which contains less than 5% (by weight of the CHO-MIN slurry) Fat in the form of triglycerides. In this example, at least 5 〇/〇 (by weight) of the total fat present in the nutrient is in the form of pre-digested fat and is added to the CHO-MIN slurry. In certain embodiments, at least 5% (by weight), including at least 10°, is included in the nutritional product. (by weight), including at least 2% by weight, including at least 30°/. (by weight), including at least 4% by weight, including at least 50% by weight, including at least 6% by weight, including at least 70°. (by weight), including at least 8% by weight, including at least 90% by weight, and including wo% by weight of total pre-digested fat is added to the CHO-MIN slurry. In a particular embodiment 'before adding pre-digested fat to the CHO-MIN slurry or in manufacturing 161219. Doc -32· 201233342 During the c_IN concentration, fat-soluble nutrients (such as mixed carotenoids or vitamins A, D, WK) are dissolved in pre-digested fat. In contrast to the cation and the mouth material, the stability of the final nutritional composition can be improved by adding pre-digested fat to the CH0_MIN stimulant. Subsequently, the resulting slurried material was blended with heating and stirred, and the pH was adjusted to 6. 6-7. 0. Thereafter, the composition is subjected to a high temperature short time (htst) process during which the composition is heat treated, emulsified and homogenized, and then allowed to cool. Add water-soluble vitamins and ascorbic acid, adjust the positive value to the desired range if necessary, add flavoring and add water to achieve the desired total solids content. The composition is then aseptically packaged to form a (iv) encapsulated nutritional emulsion. The emulsion may also be filled and subsequently sterilized to form a ready-to-feed or concentrated liquid, which may be spray dried, dry blended and/or coalesced. The nutritional solids, such as spray dried nutritional powders or dry mixed nutritional powders, can be prepared by any effective collection of techniques known or otherwise suitable for the preparation and formulation of nutritional powders. For example, when the nutritional powder is a spray dried nutritional powder, the spray drying step can similarly include any spray drying technique known or otherwise suitable for producing a nutritional powder. A variety of different spray drying methods and techniques are known; Lu Yangling is suitable for the manufacture of spray-dried nutritional powders herein. A method of preparing a spray-dried nutritional powder* comprises forming and homogenizing an aqueous slurry or liquid containing pre-digested fat and optionally containing protein, carbohydrate and other fat sources and then spray drying the material or liquid to produce a spray Dry nutrient powder () This method can further include spray drying 161219. Doc -33- 201233342 The step of drying, dry blending or otherwise adding other nutrients (including any one or more of the ingredients described herein) to the spray dried nutritional powder. Other suitable methods for preparing a nutritional product are described, for example, in U.S. Patent No. 6,365,218 (B〇rsehei et al.), U.S. Patent No. 6,589,576 (b. (10), et al.), U.S. Patent No. 6,306,908 (Carlson et al.), and U.S. Patent Application No. 20030118703 In Al (Nguyen et al.), the description thereof is incorporated herein by reference to the extent that it is incorporated herein by reference in its entirety, in accordance with the present invention and as further described below, the nutrients described herein can be used for various purposes, including, for example, improved digestion. Improve nutrient absorption, improve tolerance, reduce the incidence of necrotizing enterocolitis, reduce the incidence of abdominal pain and reduce the incidence of short bowel disease. Individuals (infants, young children, or children) who use the nutritional products described herein may actually have or suffer from the disease or condition (ie, may actually have problems with digestion, nutrient absorption and/or tolerance) or actual May have necrotizing enterocolitis, abdominal pain or short bowel disease] or may be prone to the disease or condition or the risk (ie, 'may not actually have the disease or condition, but due to certain conditions , family history, etc., increased risk compared with the general population) ^ regardless of whether the individual actually has the disease or condition, or whether there is a risk of developing the disease or condition or is prone to develop the disease or condition, the individual is This article is classified as "needed" to help resolve and combat the disease or condition. For example, an infant may actually have necrotizing enterocolitis due to premature birth or may be at risk of developing necrotizing enterocolitis (prone to necrotizing enterocolitis). Similarly, in another example, the baby is suffering from its 161,219. Doc • 34· 201233342 A disease or illness 'brother or family history with such problems may actually be resistant to (and/or digestive and/or nutrient absorption problems, or may be afflicted (easy to suffer) Or a plurality of risks of such conditions, including whether or not the individual actually has the disease or the disease, or whether there is only a risk of developing the disease or condition or is prone to develop the disease or condition, including the use of the present invention The nutritional products described herein assist the individual. Based on the above, some method embodiments of the present invention are directed to determining a particular subgroup or subclass of an individual (ie, "need" to help solve one or more of the methods described herein. a particular disease or a subgroup or subclass of individuals of a particular condition, and thus not all individuals may benefit from all of the methodologies described herein, for example, as for certain diseases or conditions, not all individuals are as described herein. Individual subgroup or subcategory. The nutritional product as described herein comprises predigested fat desirably combined with one or more other fat sources for the infant, toddler Children provide a source of nutrition for improved nutrient digestion and absorption. In particular, it is similar to the digestion of breast-fed infants because the fat source is at least partially digested before entering the duodenum, giving the baby more time to absorb nutrients' especially in the intestines. And the nutrients entering the baby's colon are reduced, thus reducing the nutrients that will be fermented and produce gas to reduce product tolerance. Therefore, by using pre-digested fat sources (such as mono-acids) in nutrients such as infant formulas Glycerides and/or fatty acids) may now provide infants with breast milk substitutes or supplements that more closely mimic the benefits of breast milk. In addition to the improved nutrient absorption as described above, it has been found in nutritional supplements 161,219. Doc -35· 201233342 uses pre-digested fat in combination with one or more water-insoluble hydrophobic compounds (such as oil-soluble (fat-soluble) vitamins (vitamins A, D, β and K), carotenoids (eg lutein, It is also helpful for the formation of micelles when administered together with β_carotene, lycopene, etc., glycolipids (neurolipids), sterols and phytochemicals. The formation of the micelles allows the insoluble hydrophobic compound to be dissolved in the digest, which is a step of intestinal villus absorption. In addition, pre-digested fat will be used to re-synthesize triglycerides to form chylomicrons. The chylomicrons carry the water-insoluble hydrophobic compound into the lymph, wherein the circulation delivers the insoluble hydrophobic compound to the target organ and/or tissue to produce the desired physiological effect. In addition to the benefits discussed above, it has been found that nutrients comprising pre-digested fat stimulate the production of cholecystokinin (CCK) in the duodenum, which stimulates pancreatic lipase production. This production leads to further digestion of nutrients and reduces contraction of the upper stomach and intestines, which allows more time for absorption. Therefore, the use of pre-digested fat in nutrients reduces the total amount of nutrients that enter the colon and are fermented and produce gas and swell. Therefore, the use of pre-digested fat in nutrients can improve tolerance by improving nutrient digestion and absorption (with less flatulence). This can be especially important for babies, as tolerance may be a question of interest in certain babies. In addition to stimulating CCK production, it has been found that pre-digested fat also induces secretion of intestinal growth hormone (glucagon-like peptide-2, GLP-2). GLP-2. It enhances intestinal maturation in infants, which results in better digestion and nutrient absorption. It has been further discovered that a nutrient containing pre-digested fat as described herein is 161,219. Doc -36- 201233342 can be used to provide a source of nutrition for infants, toddlers or children, which reduces the incidence of necrotizing enterocolitis (NEC), abdominal pain and/or short bowel disease. Additionally, in contrast to the protein in the fat slurry, the nutritional product is manufactured by adding at least a portion of the pre-digested fat (or, in some embodiments, all pre-digested fat) to the carbohydrate-mineral slurry. In the examples, the resulting stability of the nutritional product (usually in the form of a nutritional emulsion) can be improved. 0 EXAMPLES The following examples illustrate specific embodiments and/or features of the nutritional products of the present invention. The examples are given for illustrative purposes only and are not to be construed as limiting the invention, as many variations are possible without departing from the spirit and scope of the invention. All exemplified amounts are by weight based on the total weight of the composition, unless otherwise stated. An example of a mouthwash is a shelf-stable nutrient prepared according to the manufacturing methods described herein such that, unless otherwise stated, each of the illustrated products includes an example of a sterilely sterilized embodiment and a sterilized dad package. . An example of a nutrient liquid is an oil-in-water aqueous emulsion that is packaged in a 24〇〇11 plastic container and that maintains physical stability within a month of storage at a storage temperature within the coffee range after blending (five). Examples 1-4 illustrate lactose-free infant nutritional emulsions of the present invention, the knives of which are listed in the table below. Unless otherwise stated, all ingredient amounts are listed in kilograms of 1000 kilograms of batch product. 161219. Doc •37- 201233342 |Ingredients Example 1 Example 2 Example 3 I Example 4 Water Sufficient Sufficient Sufficient Sufficient Maltodextrin 53 43. 3 50 60 Sucrose 16. 5 25 19. 2 16. 38 Milk Protein Isolates 15. 65 15. 65 15. 65 15. 65 Corn oil 12 12 12 12 High oleic acid safflower oil 10 10 10 10 Single plucking glycerol from the purpose 10 9 8 7 c1 (rc24 fatty acid strontium salt 6. 0 7 8 9 Coconut oil 2 2 2 2 Fungal oil 0. 3 0. 3 0. 3 0. 3 lecithin 0. 1 0. 1 0. 1 0. 1 dipotassium hydrogen phosphate 0. 96 0. 96 0. 96 0. 96 gasification potassium 0. 3 0. 3 0. 3 0. 3 ascorbic acid 0. 235 0. 235 0. 235 0. 235 Carrageenan 0. 150 0. 150 0. 150 0. 150 potassium hydroxide 0. 136 0. 136 0. 136 0. 136 TM/UTM premix 0. 1684 0. 1684 0. 1684 0. 1684 Vitamin A, D, E premix 0. 0758 0. 0758 0. 0758 0. 0758 Water-soluble vitamin premix 0. 0728 0. 0728 0. 0728 0. 0728 Potassium moth 0. 00022 0. 00022 0. 00022 0. 00022 vaporized chromium 0. 000217 0. 000217 0. 000217 0. 000217 Examples 5-8 Examples 5-8 illustrate lactose-based nutritional emulsions of the present invention, the ingredients of which are listed in the following table. Unless otherwise stated, all ingredient amounts are listed in kg per 1000 kg batch of product. |成* Example 5 Example 6 Example 7 Example 8 Water sufficient amount sufficient amount sufficient amount lactose 58 66 71 63 non-fat dry milk 25 10 0 16 whey protein concentrate 6. 4 13 18 10. 5 High oleic acid safflower oil 14 14 14 14 161219. Doc -38 - 201233342 Coconut oil 6. 2 6. 2 6. 2 6. 2 glyceryl monopalmitate 10 8 6 4 C10-C24 fatty acid 5. 5 7. 5 9. 5 11. 5 fruit oligosaccharide / galactooligosaccharide 9 9 9 9 fungal oil 0. 3 0. 3 0. 3 0. 3 dipotassium hydrogen phosphate 0. 96 0. 96 0. 96 0. 96 NaOH Mom 0. 78 1. 07 1. 36 1. 64 potassium chloride 0. 3 0. 3 0. 3 0. 3 ascorbic acid 0. 235 0. 235 0. 235 0. 235 angle and vegetable glue 0. 150 0. 150 0. 150 0. 150 potassium hydroxide.  0. 136 0. 136 0. 136 0. 136 TM/UTM premix 0. 1684 0. 1684 0. 1684 0. 1684 Vitamin A, D, E premix 0. 0758 0. 0758 0. 0758 0. 0758 Water-soluble vitamin premix 0. 0728 0. 0728 0. 0728 0. 0728 Magnetized potassium 0. 00022 0. 00022 0. 00022 0. 00022 chromium chloride 0. 000217 0. 000217 0. 000217 0. 000217 Examples 9-12 Examples 9-12 illustrate soy-based infant nutritional emulsions of the present invention, the ingredients of which are listed in the following table. Unless otherwise stated, all ingredient amounts are listed in kilograms per 1,000 kilograms of batch product. Ingredients Example 9 Example 10 Example 11 Example 12 Water Sufficient Sufficient Sufficient Sufficient Corn Syrup Solid 53 43. 3 50 60 Sucrose 16. 5 25 19. 2 16. 38 Soy Protein Isolates 19. 5 19. 5 19. 5 19. 5 Corn oil 12 12 12 12 High oleic acid safflower oil 10 10 10 10 Monopalmitic acid glycerin 10 9 8 7 Ci (pC24 fatty acid 6. 0 7 8. 0 9 161219. Doc -39- 201233342 Fungal oil 0. 3 0. 3 0. 3 0. 3 L-cystine 2. 3 2. 3 2. 3 2. 3 L-tyrosine 1. 1 1. 1 1. 1 1. 1 Hydrogenation feed 0. 09 1. 0 1. 1 1. 2 L-tryptophan 0. 66 0. 66 0. 66 0. 66 dipotassium hydrogen phosphate 0. 96 0. 96 0. 96 0. 96 gasification potassium 0. 3 0. 3 0. 3 0. 3 anti-grear acid 0. 235 0. 235 0. 235 0. 235 Carrageenan 0. 150 0. 150 0. 0 0. 0 potassium hydroxide 0. 136 0. 136 0. 136 0. 136 TM/UTM premix 0. 1684 0. 1684 0. 1684 0. 1684 Vitamin A, D, E premix 0. 0758 0. 0758 0. 0758 0. 0758 Water-soluble vitamin premix 0. 0728 0. 0728 0. 0728 0. 0728 Potassium iodide 0. 00022 0. 00022 0. 00022 0. 00022 Examples 13-16 Examples 13-16 illustrate the hydrolyzed protein-based infant nutritional emulsions of the present invention, the ingredients of which are listed in the following table. Unless otherwise stated, all ingredients are listed in kilograms per 1000 kg batch. Ingredients Example 13 Example 14 Example 15 Example 16 Water sufficient amount sufficient amount sufficient amount of sucrose 42 42 42 42 starch 21. 8 21. 8 21. 8 21. 8 Hydrolyzed protein 22. 2 22. 2 22. 2 22. 2 high oleic safflower seed oil 13. 7 13. 7 13. 7 13. 7 MCT oil 6 6 6 6 glyceryl monopalmitate 10 9 8 7 Cl〇-C24 fatty acid 11 9. 5 8 6. 5 coconut oil 5 7. 5 9 11. 5 fungal oil 0. 3 0. 3 0. 3 0. 3 barium hydroxide 1. 6 1. 29 1. 1 0. 93 161219. Doc •40· 201233342 L-methionine 0. 3 0. 3 0. 3 0. 3 dipotassium phosphate 0. 96 0. 96 0. 96 0. 96 gasification potassium 0. 3 0. 3 0. 3 0. 3 ascorbic acid 0. 235 0. 235 0. 235 0. 235 Carrageenan 0. 0 0. 0 0. 150 0. 150 potassium hydroxide 0. 136 0. 136 0. 136 0. 136 TM/UTM premix 0. 1684 0. 1684 0. 1684 0. 1684 Vitamin A, D, E premix 0. 0758 0. 0758 0. 0758 0. 0758 Water-soluble vitamin premix 0. 0728 0. 0728 0. 0728 0. 0728 Potassium telluride 0. 00022 0. 00022 0. 00022 0. 00022 Example 17 In this example, rat absorption of C1()-C24 fatty acid calcium salt and related bioavailability was assessed. Thirty rats were randomly assigned to one of three diets containing different proteins and fats (Diet 1, Diet 2, and Diet 3). Diet 1-3 with AOAC method 906. The same applies to 48, except that diets 1-3 have a higher fat content and contain maltodextrin as a source of carbohydrates. Diet 1 contains 1 〇 wt ° / 〇 protein can be used as acid casein and contains 23 · 6 wt% fat can be used to contain 30 wt% coconut oil, 30 wt% soybean oil and 40 wt% high oleic acid safflower seed oil ( HOSO) oil blend. The nutritional forms of diets 2 and 3 are the same as those of diet 1, except that proteins, fats, carbohydrates, and minerals are mixed, homogenized, and spray dried. Diet 3 differs from Diet 2 only in that it replaces HOSO oil with high oleic acid safflower fatty acid calcium salt and replaces tricalcium phosphate with potassium phosphate so that the overall nutrition and mineral form of diet 2 diet 3 is the same. Ca-HOSO fatty acid calcium salt provides 100% dietary calcium. 161219. Doc • 41 · 201233342 Rats were fed diet 1, diet 2 or diet 3 for 4 weeks. Feed conversion (grams of weight gain/gram of feed intake) and protein efficiency ratio (grams of weight gain/gram of protein intake) (pER) were calculated using feed/protein intake and weight gain at the end of the feeding trial. If the caloric value of the HOSO fatty acid calcium salt (ie, calories per kilogram) is significantly lower than the caloric value of HOSO due to poor absorption, it is expected that rats of diet 3 will increase their body weight or take more feed to maintain it. Growth, both of which result in lower feed conversion and PER. The results shown in the table below show that rats in diet 3 have the same feed conversion or PER as the control group, indicating that the caloric value of the HOSO fatty acid calcium salt is not different from HOSO oil. Therefore, the HOSO fatty acid calcium salt is shown to be highly bioavailable. Protein efficiency ratio feed conversion ~~ diet 1 (control group 1) 2. 83 +/- 0. 28* 0. 29 +/- 0. 03 Diet 2 (Control 2) 3. 16+/-0. 17 0. 31 +/-0. 02 Diet 3 (fatty acid word salt) 3. 32+/-0. 27 0. 37 +/- 0. 03 *Standard deviation (n=10) Example 18 In this example, the absorption of soybean fatty acid salt by a 10-day-old pig was analyzed. Sixteen suckling pigs were randomly divided into two groups and individually housed in metabolic cages and trained to obtain a nutritional emulsion from the pot within 30 minutes. After one week of training with a commercially available ready-to-eat hydrolyzed protein-based formulation, the pigs were fed a commercially available hydrolyzed protein-based formula powder containing tricalcium phosphate and calcium carbonate as a source of calcium. Doc • 42 - 201233342 End (control) or emulsion containing soy fatty acid calcium as a calcium source (experimental emulsion). For the control and experimental emulsions, the protein source and content, fat content and mineral form were the same. However, the experimental emulsion contained soybean oil as a substitute for soybean oil in the control group and contained calcium hydroxide as part of the calcium mineral system to neutralize the soybean fatty acid. The potassium phosphate content of the experimental emulsion was adjusted to match the phosphorus content of the control group. Soy fatty acid calcium provides 100% calcium in the experimental emulsion. After two weeks of feeding, the apparent fat and calcium digestibility were calculated based on the following formula: Apparent fat digestibility = ((fat intake - fecal fat) / fat intake) * i00 Apparent digestibility = ((弼 ingestion - Fecal sputum) / dance intake) * i 物质 dry matter digestibility = ((dry matter intake - fecal dry matter) / dry matter intake) *100 Reduced feed conversion (weight / feed intake) and reduced fat, Calcium and dry matter digestibility will show poor absorption of the soy fatty acid calcium salt of the experimental emulsion, and thus it is shown that for the experimental emulsion, the caloric value and bioavailability of calcium are lower than in the control group. As shown in the table below, the feed conversion, fat digestibility and dry matter digestibility of the experimental emulsions were significantly different from those of the control group, indicating that for newborn pigs, the soy fatty acid calcium salt of the experimental emulsion was highly absorbed and bioavailable. In addition, the apparent calcium digestibility data shown below shows that the soy fatty acid calcium salt of the experimental emulsion is more bioavailable than the calcium contained in the control (i.e., 'tricalcium phosphate and calcium carbonate). 161219. Doc -43- 201233342 Apparent fat Digestibility Feed conversion (weight gain grams/feed (dry matter) grams) Apparent calcium digestibility Apparent dry matter Digestibility Control group 97. 6+/- 1. 0 0. 82 +/- 0. 14* 81. 8+/-7. 2 97. 8 +/- 0. 7 Experimental emulsion 97. 6+/- 1. 4 0. 80+/-0. 15 91. 3+/-3. 3 98. 0+/-1. 0 * standard deviation (n = 10) Example 19 In this example, the emulsification characteristics of the fatty acid calcium salt were analyzed.丨 8 g 130°F soybean oil containing glycerol monopalmitate (5 wt% oil) and 43 mg mg Ca (tricalcium phosphate form) by using a table top high shear mixer To prepare a first emulsion (control emulsion). A second emulsion (calcium fatty acid emulsion) containing the same amount of calcium and fat (12 g of soybean oil plus 6 g of soy fatty acid) as a control emulsion was prepared by: (1) at a temperature of about 130 °F Dispersing the soybean fatty acid oil solution in water; (2) adding 430 mg of Ca in the form of calcium carbonate; (3) adjusting the pH of the solution to about 7. using KOH. 0; and (4) shear the mixture using a tabletop high shear mixture. The control emulsion and the fatty acid calcium emulsion were allowed to stand for three weeks to analyze the emulsion separation. After one night, the control emulsion showed visible phase separation containing a milky layer on top of the emulsion. (See Figure 1A). In contrast, after three weeks of storage, the fatty acid emulsion had only a slightly detectable (but not clearly visible) soap layer on top of the emulsion while the emulsion remained in one phase. There was no visible calcium deposition at the bottom of the fatty acid emulsion (see Figure 1B). These results show that the fatty acid salt is an effective emulsifier and can be substantially 161,219. Doc -44 - 201233342 Does not provide a source of calcium from the nutritional emulsion of solution settling. This results in improved stability and long shelf life of the emulsion product. Example 20 In this example, the fat uptake and calcium uptake of two independent test formulations and control formulations were measured for 1 day old pig. The first test formulation (Formulation 1) contained palm oil essential oil in the fat system 'The second test formulation (Formulation 2) contained pre-digested fat in the fat system' and the control formulation (Formulation 3) in the fat The system contains low-profile acid oil. The fat system components of the three formulations are listed in the table below. Nutrients (g) Formulation 1 (palm oil essential oil formulation) Formulation 2 (pre-digested fat formulation) Formulation 3 (control formulation containing low palmitic acid oil) Coconut oil 37. 2 0 84. 1 Shangyou sour safflower oil 62. 8 108 111. 9 Soybean fatty acids 0 56. 9 0 ARA oil 3. 03 3. 03 3,03 DHA oil 1. 52 1. 52 1. 52 glyceryl monopalmitate 0 65. 4 0 lecithin 1. 12 1. 12 1. 12 Palm oils 122. 7 0 0 Soybean oil 57. 1 0 83. 8 Preparation of three formulations with nearly identical nutrients and mineral forms. The fatty acid form of Formulations 1 and 2 mimics the fatty acid form of the breast milk. Formulation 2 contains calcium hydroxide (amount sufficient to sequester all free fatty acids) as a source of calcium which reacts with the soy fatty acid to form an insoluble fatty acid calcium salt. This reaction eliminates the bitter taste and throat burning sensation produced by free fatty acids. Another 161219. Doc • 45 - 201233342 In addition, the potassium phosphate content of Formulation 2 was raised to match the phosphorus content of Formulations 1 and 3. The calcium salt used in Formulations 1 and 3 is calcium phosphate. Sixty one day old pigs (plus or minus two days) were randomized to receive Formulation 1, Formulation 2, or Formulation 3. Pigs were individually housed in metabolic cages and fed five times a day for three weeks after training and acclimation for 4 days. Fecal material from day 2 to day 8 was collected and analyzed for calcium absorption and fat absorption. Calcium absorption is calculated by dividing the amount of calcium in the fecal material + the amount of calcium in the diet and multiplying by 100. The fat absorption is calculated by dividing the amount of fat in the fecal material by the amount of fat in the diet and multiplying by 1%. The results are shown in the table below. Fat Absorption (%) Calcium Absorption Formulation 1 (palm oil) 92. 3 ±3. 9 88. 9 士 4. 7 Formulation 2 (pre-digested fat) 98. 2 ± 0. 7 93. 1 ± 2. 4 Formulation 3 (control: low brown citrate fat system) 98. 0 ± 1. 4 90. 7 ±3. 5 As shown in the results in the table above, the use of a pre-digested fat system allows the infant formula to mimic the fatty acid profile of the breast without the adverse effects of calcium and fat absorption experienced when using the palm olein oil system. The fat and barium absorption rate of Formulation 2 (pre-digested monthly fat-supplemented formulation) is at least as good as the monthly fat and about the absorption rate of the low-brown acid-picking formula. These findings indicate that soy fatty acid calcium salts are highly bioavailable in newborn pigs. Example 21 In this example, the post-prandial increase in CCK production (AUC) and enterokin production (AUC) of pigs of Example 20 was evaluated. In the conclusion of the fat and calcium absorption analysis described in Example 20, it was cast 161,219. Doc -46 - 201233342 Pigs with Formulation 2 (pre-digested fat formulation) or Formulation 3 (including low palmitic acid control formulation) were fasted for 12 hours and fasted blood was drawn to separate the serum. The pigs were allowed to recover for two hours and then 250 mL of Formulation 2 or Formulation 3 was administered. Postprandial blood samples were taken 30 and 6 minutes after feeding and CCK and enterin were calculated to calculate the postprandial increase in CCK (area under the curve) and enterin (AUC). The results are shown in the table below. Formulation 2 (pre-digested fat formulation) (pg/mL*min) Formulation 3 (control: low palmitic acid formulation) (pg/mL*min) Post-prandial increase in CCK secretion (area under the curve) 1935 ± 1464 1046 ±754 Enterin AUC (post-prandial increase) 483±253 839±403 The data in the above table shows that replacing pre-digested fat (monopalmitin plus soy fatty acid) with triglyceride stimulates postprandial CCK Secretion 'It has been shown to stimulate pancreatic digestive enzyme secretion, enhance gallbladder contraction and delay oral to cecal delivery. Therefore, formulations with pre-digested fat stimulate more digestive enzyme secretion and slow GI delivery to allow more nutrient digestion and absorb. Therefore, formulations containing pre-digested fat can improve formulation tolerance&apos; because undigested nutrients can cause excessive colonic fermentation leading to flatulence, diarrhea and bloating. In addition, the information in the above table shows that replacing pre-digested fat (monoglyceride plus soybean fatty acid) with triglyceride can reduce postpartum enterokin secretion. Infants with abdominal pain have been shown to have lower post-prandial CCK levels but higher post-prandial enterin levels. This kind of intestinal hormone between meals is not 161219. Doc -47- 201233342 Balance causes GI contraction in infants' which causes abdominal pain. The data in the above table shows that the inclusion of pre-digested fat can increase the CCK content of the baby after a meal, but reduce the intestinal motility, thereby reducing the hormone imbalance to relieve GI contraction, abdominal pain and abdominal pain. Example 22 In this example, the pig of Example 20 was used to study the effect of various fat systems on the yoghurt particulate triglyceride pantothenic acid and the Sn-2 shelf acid content. One hour postprandial blood samples were taken from each pig and plasma was separated, frozen in liquid nitrogen, and stored in a freezer at -80 °C. Total plasma lipids were extracted using Folch solvent. The triglyceride was separated by thin layer chromatography. The table below shows the plasma triglyceride palmitate and Sn-2 palmitic acid in Formulation 1 (palm oil blend formulation) and Formulation 2 (pre-digested fat formulation). The table also shows chylomicron triglycerides and Sn-2 palmitic acid in pigs fed the two formulations. Formulation 1: (Brown olein) Plasma triglyceride formulation of silver feed formulation 1 : (pre-digested fat) Pigs fed with Formulation 2 plasma triglyceride for cooking human breast milk Infant plasma triglyceride triglyceride vinegar Sn-2 triglyceride vinegar Sn-2 triglyceride Sn-2 triglyceride Sn-2 triglyceride Sn-2 palmitic acid content (%) 23 . 3 5. 8 18. 3 10. 6 21. 4 5. 2 18. 5 14. 4 25 25. 5 As shown in the table above, the plasma levels of triglyceride and Sn-2 palmitic acid in pigs fed the pre-digested fat formula were significantly higher than those fed the palm olein formula. The ratio of plasma triglyceride palmitate/Sn-2 palmitic acid of Formulation 1 and Formulation 2 was about 1. 7 and 1. 3, and the ratio of breast milk to infants is known to be about 1. 1. Therefore, this data shows that pre-digested fat formulations mimic breast milk better than palm oil fat blends. 161219. Doc •48- 201233342 Example 23 In this example, the pig of Example 2G was used to study the effect of various fat systems on the blood lutein content. The plasma from the i-hour postprandial blood sample of each pig was extracted using a solvent of methanol and methanol (ratio of 2:1), the solvent was removed, and the obtained lipid was collected and analyzed for lutein by a % method. The following table shows the lutein content of pigs fed the formulation 丨 (palm oil extract), formulation 2 (pre-digested fat formulation) and formulation 3 (low palmitic acid formulation), per mg of lipid The number of lutein (four) is expressed. Formulation 1: (Brown olein) Formulation 2: (Pre-digested fat) Formulation 3: (Low palmitic acid) Lutein content N/A* 0. 765 pg 0. 539 pg * Formulation 1 has a low xanthophyll content and is difficult to measure. As shown in the above table, pigs fed a formulation containing pre-digested fat had an increased lutein absorption compared to pigs fed a formulation containing palm olein or low palmitic acid. Example 24 In this example, the formulation of Example 20 was used. 2 (pre-digested fat formulations) and formulation 3 (low palmitic acid formulations) to study the effects of various fat systems on the lutein content of the cells. Reconcile Formulation 2 and Formulation 3 with water (per 1. 0 L water 133 g powdered formulation) and the addition of HC1 adjusted the pH of the reconstituted formulation to 4. 5. The reconstituted formulation was digested for 1 hour at room temperature by adding i_〇〇 ml USP pepsin (56 mg/mi) to the 40 ml reconstituted formulation* after pepsin digestion 161219. Doc -49- 201233342 Adjust the pH of the reconstituted formulation to 7. 0, and then a mixture of 28 mg USP trypsin/protease, 28 mg USP trypsin lipase and 1 08 mg bile extract was added to the pepsin digested formulation. The formulation was further digested for 2 hours at room temperature and centrifuged (31,000 g, 3 hours at 20 eC). The digested formulation forms an oil/fat clot, an aqueous phase, and a sedimentation layer. The aqueous phase is drawn for lutein analysis of the micelles which serve as a carrier during the absorption of lutein in the aqueous cavity. The table below shows the content of lutein in the cells per kg of digestion formulation. Digestion Formulation 2 : (Pre-digested fat) Digestive Formulation 3 : (Low palmitic acid) Microcytosin (pg) 0. 598 pg 0. 246 μξ As shown in the table above, the amount of lutein found in the digested formulation containing pre-digested fat was more than twice the amount of lutein found in the digested formulation containing low brown acid. 'This shows that the use of pre-digested fat can increase lutein absorption. Example 25 In this example, the ability of pre-digested fat to reduce the incidence of soft stools was analyzed. Thirty weaned rats were fed a hydrolyzed protein-based powdered infant formula (containing MCT oil as a 3 wt% fat source) for a four-day acclimation period. In the adaptation period, hehe. At the time of the bundle, the rats were randomly divided into two groups and fed a control formulation (low-standard palmitic infant formula) or a test formulation (infant formula containing pre-digested fat). Control compound and test formulation nutrients. The type is the same. Rats were given free access to feed and water for five days, and the amount and weight of the ingested feed were recorded daily. 161219. Doc 201233342 Although there was no significant difference in feed intake or weight gain between the two groups, there was a significant difference in stool firmness. During the last two days of feeding, the rat's stool firmness score was scored using the 〇_5 point system based on the severity and firmness of the stool bonded to the pet-absorbent sheet. A score of 0 indicates normal.  Stool and a 5-point value indicate watery diarrhea. As shown in Figure 2, the arrogant feed is clear.  Rats with ligands (containing MCT oil) produced thinner stools than rats fed the test formulation (containing pre-digested fat). Example 26 In this example 'analysis of the ability of pre-digested fat to reduce the incidence of necrotizing enterocolitis (NEC). Preterm pigs (92% of gestation) delivered via caesarean section were immediately transferred to an oxygenation incubator (37 ° C) and a vascular catheter was placed in the umbilical artery. The pigs were injected three times (4, 6 and 7 mL/kg body weight) of maternal plasma via a vascular catheter during the first 24 hours. Total parenteral nutrition (TPN) was provided at a rate of 4-6 mL/kg per hour for 24 hours. The pigs were then randomized to receive a control formulation or a pdf formulation via an orgastric tube at a rate of 5 mL/kg per hour. The control formulation was identical to the pDF formulation except for the fat system therein. Special . 脂肪, s, the fat system in the control formulation comprises vegetable oil, and the fat system in the pDF formulation comprises 3 〇 wt% glycerol monopalmitate ' 2 〇 wt% large ugly acid, 26 wt ° /. High oleic safflower seed oil, 丨 4 wt% coconut oil and 1 〇 wt0/. Both the glyceryl dibutyrate control formulation and the pDF formulation per liter formulation contained 100 g protein, 47 g fat, and 50 g corn syrup. The pigs were euthanized after anesthesia for 36 hours and subjected to autopsy to use 161219. Doc 201233342 The 1-5 scoring system assesses the severity of NEC lesions, with a score of 1 indicating no signs of NEC. The results are shown in the table below. Block 1 Block 2 Control PDF Control PDF Formulation Formulation (n=5) (n=3) (n=5) (n=3) Early NEC Death 2 0 3 1 Attestation at Autopsy NEC 2 1 0 0 Total NEC 4 1 3 1 As shown in the table above, 5 of the 10 pigs fed the control formulation (50%) died of NEC before the end of the enteral feeding period, but fed Only 1 of the 6 pigs in the PDF formulation (16. 7%) died of NEC before the end of the enteral feeding period. In addition, 7 of the 10 pigs fed the control formulation (70%) had NEC measured before the end of the enteral feeding period, while only 2 of the 6 pigs fed the PDF formulation (33) %) NEC was determined before the end of the enteral feeding period. It can therefore be concluded that the incidence of NEC can be reduced by replacing the vegetable oil fat system with a fat system containing pre-digested fat. BRIEF DESCRIPTION OF THE DRAWINGS Figures 1A and 1B show graphical representations of a control emulsion and an experimental emulsion prepared as in Example 19. Figure 2 is a graph showing the effect of diet on fecal firmness. 161219. Doc -52-

Claims (1)

201233342 七、申請專利範園·· 1. 一種降低取分、&amp; Λ上 - 兄幼兒或孩童之壞死性小腸結腸炎發生率 〉、太 ’該方法包括向該嬰兒、幼兒或孩童投與包含至 t /〇之至少一種游離腊肪酸組分、含有脂肪酸之單 酸甘油酯或其組合之營養品。 2.如請求 士·、A ^ 之方法’其中該等含有脂肪酸之單酸甘油酯 為單棕櫚酸甘油酯。 3 . 如請求項1 ^ , 〈万法’其中該游離脂肪酸組分呈選自由脂 肪酸妈鹽、脂肪酸鎮鹽及其組合組成之群的形式。 4· 如請求頊 巧I万法’其中該游離脂肪酸組分包含小於i 5 t/o之具有超過14個碳原子之鏈長度的飽和脂肪酸。 5·如凊求項1之方法,其中該游離脂肪酸組分係源自植物 油。 +青托項5之方法,其中該植物油係選自由橄欖油、芥 化籽油、玉米油、大豆油及其組合組成之群。 7.如請求項6之方法,其中該植物油為大豆油。 8·如凊求項!之方法’其中該游離脂肪酸組分係源自其中 肉旦蔻酸、棕櫚酸及硬脂酸總量小於20%(以重量計)之 動物脂肪分離物。 、種降低4c兒、幼兒或孩童之腹痛發生率之方法,該方 ^包括向該嬰兒、幼兒或孩童投與包含至少10 wt%之至 ::種游離脂肪酸組分、含有脂肪酸之單酸甘油醋或其 組合之營養品。 10·如睛求項9之方法,其中該等含右 丹丫哥3有知肪酸之單酸甘油酯 161219.doc 201233342 為單棕棚酸甘油酯。 11·種降低嬰兒、幼兒或孩童之短腸症發生率之方法,該 方法包括向該嬰兒、幼兒或孩童投與包含至少10 wt%之 至少一種游離脂肪酸組分'含有脂肪酸之單酸甘油酯或 其組合之營養品。 12. 如請求項11之方法,其中該等含有脂肪酸之單酸甘油酯 為單棕櫊酸甘油酯。 13. 如請求項π之方法,其中該游離脂肪酸組分呈選自由脂 肪酸鈣鹽、脂肪酸鎂鹽及其組合組成之群的形式。 14. 如請求項11之方法,其中該游離脂肪酸組分包含小於0 wt0/❶之具有超過14個碳原子之鏈長度的飽和脂肪酸。 1 5.如請求項11之方法,其中該游離脂肪酸組分係源自植物 油0 161219.doc201233342 VII. Applying for a patent garden · 1. A reduction in the score, &amp; Λ上 - incidence of necrotizing enterocolitis in a child or child >, too 'This method includes including the baby, child or child A nutritional product of at least one free fatty acid component to t/〇, a fatty acid-containing monoglyceride or a combination thereof. 2. The method of claim A, A ^ wherein the fatty acid-containing monoglyceride is glyceryl monopalmitate. 3. The claim 1 ^ , < 10000 </ RTI> wherein the free fatty acid component is in the form of a group selected from the group consisting of fatty acid salts, fatty acid salts, and combinations thereof. 4. The method of claim 1 wherein the free fatty acid component comprises less than i 5 t/o of a saturated fatty acid having a chain length of more than 14 carbon atoms. 5. The method of claim 1, wherein the free fatty acid component is derived from vegetable oil. + The method of claim 5, wherein the vegetable oil is selected from the group consisting of olive oil, mustard seed oil, corn oil, soybean oil, and combinations thereof. 7. The method of claim 6, wherein the vegetable oil is soybean oil. 8. The method of claim </ RTI> wherein the free fatty acid component is derived from an animal fat isolate wherein the total amount of dandylic acid, palmitic acid and stearic acid is less than 20% by weight. a method for reducing the incidence of abdominal pain in 4c, a child or a child, the method comprising administering to the infant, toddler or child a monoglyceride comprising at least 10% by weight of: a free fatty acid component, a fatty acid containing fatty acid Nutritional products of vinegar or a combination thereof. 10. The method of claim 9, wherein the monoglyceride having a fatty acid is 161219.doc 201233342 is a single palm glyceride. 11. A method of reducing the incidence of short bowel disease in an infant, a child or a child, the method comprising administering to the infant, toddler or child at least one free fatty acid component comprising at least 10% by weight of a fatty acid-containing monoglyceride Or a combination of nutrients. 12. The method of claim 11, wherein the fatty acid-containing monoglyceride is glyceryl monopalmitate. 13. The method of claim π, wherein the free fatty acid component is in the form of a group selected from the group consisting of calcium salt of fatty acid, magnesium salt of a fatty acid, and combinations thereof. 14. The method of claim 11, wherein the free fatty acid component comprises less than 0 wt0/❶ of a saturated fatty acid having a chain length of more than 14 carbon atoms. The method of claim 11, wherein the free fatty acid component is derived from vegetable oil 0 161219.doc
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