TW201300111A - 預防及/或治療皮膚病況及皮膚疾病之組合物 - Google Patents
預防及/或治療皮膚病況及皮膚疾病之組合物 Download PDFInfo
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- TW201300111A TW201300111A TW100142958A TW100142958A TW201300111A TW 201300111 A TW201300111 A TW 201300111A TW 100142958 A TW100142958 A TW 100142958A TW 100142958 A TW100142958 A TW 100142958A TW 201300111 A TW201300111 A TW 201300111A
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- composition
- milk
- skin
- oligosaccharide
- lactosamine
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Abstract
本發明揭示一種組合物,其包含至少一種N-乙醯基-乳糖胺、至少一種唾液酸基化寡醣及至少一種岩藻醣基化寡醣,該組合物用於預防及/或治療皮膚病況及皮膚疾病。較佳地,該組合物係初生嬰兒配方(starter infant formula)。該皮膚疾病具體而言係異位性皮膚炎。
Description
本發明係關於組合物,其用於預防及/或治療皮膚病況(例如,促進皮膚健康)及皮膚疾病(尤其異位性皮膚炎)。
異位性皮膚炎係慢性發癢性皮膚疾病,其在兒童中常見但可在任何年齡發生。其亦稱為濕疹或異位性濕疹。在年幼兒童年齡組中食物過敏與異位性皮膚炎密切相關,且經常懷疑患有異位性皮膚炎之兒童係食物過敏。
異位性皮膚炎通常發生在具有異位傾向之人中。此意味著,該等個體可能出現以下三種緊密關聯之病況中之任一或所有病況:異位性皮膚炎、氣喘及枯草熱(過敏性鼻炎)。
異位性皮膚炎之現象如以下所述而發生。皮疹中之敏感性皮膚部位因應某些誘發物而發紅。該等誘發物因人而異。在嬰兒及年幼兒童情形中,應當心之常見誘發物之清單包括牛乳及嬰兒配方之其他可能成份(例如,小麥或大豆)。異位性皮膚炎可變成惡性循環。某物刺激兒童皮膚,使其發紅並發炎。因其發癢,兒童會抓撓該處,從而加重皮膚發炎。皮膚之外保護層喪失,且受影響區甚至對刺激物變得更敏感並容易變乾。嬰兒繼續暴露於最初誘發該等發作之事物。皮疹進一步發展且循環自身持續進行。
異位性皮膚炎無已知的單一原因。其可能反映一種以上病況。關於潛在機制有許多理論。當前研究正在調查聚角蛋白微絲蛋白(filaggrin)基因突變、皮膚細胞(角化細胞)之缺陷、免疫系統、皮膚表面微生物(細菌、病毒及酵母菌)及許多其他因素之作用。
所有皮膚病況及皮膚疾病皆可影響一般人群或具有過敏風險之人群或過敏性(因此患病)人群。
該等皮膚病況及皮膚疾病、且具體而言異位性皮膚炎對嬰兒、幼兒或兒童之影響尤其重大,此乃因其具有經歷強烈生長及增殖階段之敏感性皮膚,從而致使其甚至更易受皮膚疾病影響。家族中無過敏史且變得過敏之嬰兒群體正在增加。
低致敏性食品係一類不太可能引起過敏反應之食物。已研發出尤其用於嬰兒配方之低致敏性食品,此乃因嬰兒及兒童在其生命之最初幾個月/年中出現過敏之可能性正逐漸增大。
低致敏性嬰兒配方係用於幫助嬰兒及偶爾年幼兒童,預防及治療其過敏疾病且尤其食物過敏。其通常不使用諸如小麥、大豆及乳製品等常見過敏原來製備。其亦通常源自牛乳,然而由於其蛋白質之分解方式,大多數嬰兒對其耐受良好。
低致敏性嬰兒配方通常分為三個主要品種:部分水解、廣泛水解及基於游離胺基酸。水解嬰兒配方中之較大蛋白質鏈分解成易於消化之較短蛋白質,而游離胺基酸配方完全不包括蛋白質鏈,但含有所有基礎胺基酸。部分水解嬰兒配方與廣泛水解嬰兒配方之不同在於其蛋白質鏈可更長。低致敏性嬰兒配方之缺點在於其成本遠高於常規牛乳配方之成本。
然而,業內仍需要低致敏性嬰兒配方來預防及/或治療嬰兒及甚至年幼兒童可能出現之皮膚病況及皮膚疾病(尤其異位性皮膚炎)。
人乳寡醣(HMO)共同係人乳中之第三大固體組份,位於乳糖及脂肪之後。HMO通常由還原端之乳糖及非還原端之碳水化合物核心(通常含有岩藻醣或唾液酸)組成。已分離且表徵大約100種乳寡醣,然而,該等寡醣僅佔其餘待表徵寡醣總數之極小部分。
在過去,出於不同目的使用HMO成份來研發嬰兒配方,例如岩藻醣基化寡醣、乳-N-四醣、乳-N-新四醣或唾液酸基化寡醣。
來自Abbott Laboratories之EP 0 975 235 B1闡述包含一或多種人乳寡醣之合成營養組合物,其中組合物中之HMO選自八種HMO(3-岩藻醣基乳糖、乳-N-岩藻五醣III、乳-N-岩藻五醣II、二岩藻醣基乳糖、2'-岩藻醣基乳糖、乳-N-岩藻五醣I、乳-N-新四醣及乳-N-岩藻五醣V)之群,其中該組合物意欲用於以下情形:正常健康嬰兒、兒童、成人或具有特殊需求之個體,例如彼等伴隨某些病理病況者。此歐洲專利陳述,一般而言,寡醣保護嬰兒免於呼吸道、胃腸道及泌尿-生殖道之病毒及細菌感染。未提及關於異位性皮膚炎問題及更一般而言預防及/或治療皮膚疾病之問題。
自前述內容可看出,業內需要有效營養組合物以尤其在嬰兒及年幼兒童中預防繼發性異位性皮膚炎或促進皮膚健康,且其可便利並安全地投與。
業內需要藉由與虛弱個體(例如嬰兒或幼兒)相容且並非基於藥物之干預來改善皮膚病況或皮膚疾病(例如異位性皮膚炎)。
業內需要降低該等皮膚病況及皮膚疾病之頻率、發生率、嚴重性及/或持續時間之長期效應。此外,業內需要「在以後之生活中」、尤其係在干預後數年變得可量測之效應。
業內需要目標定為具有或不具有過敏風險之嬰兒、幼兒及兒童之食物干預,其尤其誘導皮膚上之過敏表現之降低。
業內需要該誘導皮膚健康之維持或改善之干預。
本發明者已驚奇地發現,投與特定人類寡醣之混合物可尤其有效地用於預防及/或治療皮膚病況及皮膚疾病,且具體而言用於預防及/或治療異位性皮膚炎及/或用於促進皮膚健康。
因此,本發明提供組合物,其包含至少一種N-乙醯基乳糖胺、至少一種唾液酸基化寡醣及至少一種岩藻醣基化寡醣,該組合物用於預防及/或治療皮膚病況及皮膚疾病,較佳異位性皮膚炎。
組合物較佳係合成營養組合物。組合物作為合成營養組合物包含三種不同類型之用途。在第一種情形中,個體且尤其嬰兒係健康的,且由於家族中無過敏史而不具有任何過敏風險。在第二種情形中,個體且尤其嬰兒係健康的,但由於家族中有過敏史而具有過敏風險。在第三種情形中,個體且尤其嬰兒具有過敏性,且因此患病。第一種情形係本發明之較佳目標。
本文中所用之以下術語具有以下含義。
術語「嬰兒」意指年齡在12個月以內之兒童。
術語「年幼兒童」意指年齡介於1歲與3歲之間之兒童。
術語「嬰兒配方」意指意欲用於在生命之最初4個月至6個月期間之嬰兒之特定營養用途且本身滿足此類人之營養要求之食品(1991年5月14日關於嬰兒配方及較大嬰兒配方(follow-up formula)之歐洲委員會指令(European Commission Directive) 91/321/EEC第1.2條)。
術語「較大嬰兒配方」意指意欲用於年齡超過4個月之嬰兒之特定營養用途且構成此類人逐漸多樣化之飲食中之主要液體要素之食品。
術語「初生嬰兒配方(starter infant formula)」意指意欲用於在生命之最初4個月期間之嬰兒之特定營養用途之食品。
術語「幼兒食物」意指意欲用於在生命第1年期間之嬰兒之特定營養用途之食品。
術語「嬰兒穀類組合物」意指意欲用於在生命第1年期間之嬰兒之特定營養用途之食品。
術語「成長乳」意指適應年幼兒童之特定營養需求之基於乳之飲品。
術語「離乳期」意指藉由嬰兒飲食中之其他食物替代母乳之階段。
術語「皮膚疾病」意指異位性皮膚炎及其他相關皮膚問題。濕疹係異位性皮膚炎。
術語「預防及/或治療皮膚疾病」意指預防皮膚疾病(即,異位性皮膚炎及其他相關皮膚問題、具體而言異位性皮膚炎)及降低其頻率及/或發生率及/或嚴重性及/或持續時間。發生率係指任何皮膚疾病之數量。頻率係指同一皮膚疾病之數量。此預防涵蓋降低該等皮膚疾病在以後之生活中之頻率及/或嚴重性。術語「在以後之生活中」涵蓋干預終止後之效應。「在以後之生活中」之效應較佳可係該干預終止後2週至4週、2個月至12個月或2年至12年(例如,2年、5年、10年)。
術語「皮膚病況」意指刺激、阻塞皮膚或使皮膚發炎之病況。皮膚病況可引起皮膚疾病之症狀,例如發紅、腫脹、發熱及發癢。
術語「預防及/或治療皮膚病況」意指促進皮膚健康及/或預防皮膚脫水及/或增強皮膚水合及/或降低皮膚皮疹、粗糙及/或乾燥。此預防進一步涵蓋確立顯性或隱性表現型,該表現型伴隨該等皮膚病況在以後之生活中之頻率、發生率、嚴重性及/或持續時間之降低。
術語「增強對過敏原之口服耐受性」意指當口服時降低對過敏原之敏感性。
術語「營養組合物」意指給予個體營養之組合物。此營養組合物通常係口服或靜脈內服用,且其通常包括脂質或脂肪來源及蛋白質來源。
術語「合成混合物」意指藉由化學及/或生物方式獲得之混合物,其可在化學上與哺乳動物乳中天然存在之混合物相同。只要至少一種組合物組份係藉由化學及/或生物(例如,酶)方式獲得,即可稱該組合物係合成組合物。
術語「低致敏性營養組合物」意指不太可能引起過敏反應之營養組合物。
術語「唾液酸基化寡醣」意指具有唾液酸殘基之寡醣。
術語「岩藻醣基化寡醣」意指具有岩藻醣殘基之寡醣。
術語「益菌生」意指不可消化性碳水化合物,其藉由選擇性刺激人類結腸中之健康細菌(例如雙歧桿菌(bifidobacteria))之生長及/或活性來有益地影響宿主(Gibson GR、Roberfroid MB.Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J Nutr. 1995;125:1401-12)。
術語「益生菌」意指對宿主之健康或身體狀況具有有益效應之微生物細胞製劑或微生物細胞組份(Salminen S、Ouwehand A.、Benno Y.等人,「Probiotics: how should they be defined」Trends Food Sci. Technol. 1999:10 107-10)。
「過敏」係已由內科醫師檢測到並可以不定時方式或以更持久方式治療之過敏。
除非另有說明,否則所有百分比均以重量計。
本發明組合物較佳係低致敏性組合物。
該組合物含有至少一種N-乙醯基-乳糖胺。換言之,本發明組合物含有N-乙醯基-乳糖胺及/或含有N-乙醯基-乳糖胺之寡醣。含有N-乙醯基-乳糖胺之適宜寡醣包括乳-N-四醣(LNT)及乳-N-新四醣(LNnT)。
因此,根據本發明,N-乙醯基-乳糖胺較佳選自包含乳-N-四醣(LNT)及乳-N-新四醣(LNnT)之群。
如(例如)在美國專利第5,288,637號及WO 96/10086中所闡述,LNT及LNnT可藉由使用醣基轉移酶將醣類單元自供體部分酶促轉移至受體部分來化學合成。另一選擇為,如在Wrodnigg,T.M.;Stutz,A.E.(1999) Angew. Chem. Int. Ed. 38:827-828中所闡述,LNT及LNnT可藉由將游離或結合至寡醣(例如,乳酮醣)之酮基-己醣(例如,果醣)化學轉化為N-乙醯基己醣胺或含N-乙醯基己醣胺之寡醣來製備。然後可將以此方式產生之N-乙醯基-乳糖胺轉移至作為受體部分之乳糖。
較佳地,本發明組合物以乾重計,每100 g組合物含有0.1 g至3 g N-乙醯基-乳糖胺。
根據本發明,唾液酸基化寡醣選自包含3'-唾液酸基乳糖及6'-唾液酸基乳糖之群。較佳地,3'-唾液酸基乳糖及6'-唾液酸基乳糖二者均存在於該組合物中。在此實施例中,3'-唾液酸基乳糖與6'-唾液酸基乳糖之間之比率較佳在介於5:1與1:2之間之範圍內。
3'-及6'-形式之唾液酸基乳糖可藉由層析或過濾技術自天然來源(例如動物乳)中分離。另一選擇為,其可藉由生物技術方法,使用特定唾液酸基轉移酶或唾液酸酶(神經胺酸酶),藉由基於酶之發酵技術(重組或天然酶)、藉由化學合成或藉由微生物發酵技術來產生。在後一情形中,微生物可表現其天然酶及受質或可經改造,以產生各別受質及酶。可使用單一微生物培養物或混合培養物。可由受體受質自聚合度(DP)=1往前之任一聚合度為起點開始形成唾液酸基寡醣。另一選擇為,唾液酸基乳糖可藉由化學合成法,自乳糖及游離N'-乙醯基神經胺酸(唾液酸)來產生。唾液酸基乳糖亦可購自(例如)Kyowa Hakko Kogyo(日本)。
較佳地,本發明組合物以乾重計,每100 g組合物含有0.05 g至2 g,更佳為0.1 g至2 g之唾液酸基化寡醣。
岩藻醣基化寡醣可選自包含以下之群:2'-岩藻醣基乳糖、3-岩藻醣基乳糖、二岩藻醣基乳糖、乳-N-岩藻五醣(換言之,乳-N-岩藻五醣I、乳-N-岩藻五醣II、乳-N-岩藻五醣III及乳-N-岩藻五醣V)、乳-N-二岩藻六醣I、岩藻醣基乳-N-六醣、二岩藻醣基乳-N-六醣I及二岩藻醣基乳-N-新六醣II。尤佳岩藻醣基化寡醣係2'-岩藻醣基乳糖(2 FL)。
岩藻醣基化寡醣可藉由層析或過濾技術自天然來源(例如動物乳)中分離。另一選擇為,其可藉由生物技術方法,使用特定岩藻醣基轉移酶及/或岩藻醣苷酶,經由使用基於酶之發酵技術(重組或天然酶)或微生物發酵技術來產生。在後一情形中,微生物可表現其天然酶及受質,或可經改造以產生各別受質及酶。可使用單一微生物培養物及/或混合培養物。可由受體受質自聚合度(DP)=1往前之任一聚合度為起點開始形成岩藻醣基化寡醣。另一選擇為,岩藻醣基化寡醣可藉由化學合成自乳糖及游離岩藻醣產生。岩藻醣基化寡醣亦可購自(例如)Kyowa Hakko Kogyo(日本)。
較佳地,本發明組合物以乾重計,每100 g組合物含有0.1 g至3 g岩藻醣基化寡醣。
在較佳實施例中,本發明組合物中,每100 g組合物包含總量為0.05 g至3 g之N-乙醯基化乳糖胺、唾液酸基化寡醣及岩藻醣基化寡醣。
本發明組合物可進一步包含至少一種益生菌菌株,該益生菌菌株較佳係雙歧桿菌(Bifidobacteria)及/或乳酸桿菌(Lactobacilli)。
適宜益生菌菌株包括以商標LGG得自Valio Oy(芬蘭)之鼠李醣乳酸桿菌(Lactobacillus rhamnosus) ATCC 53103、鼠李醣乳酸桿菌CGMCC 1.3724、類乾酪乳酸桿菌(Lactobacillus paracasei) CNCM I-2116、由BioGaia A.B以商標Reuteri出售之路氏乳酸桿菌(Lactobacillus reuteri)、約氏乳酸桿菌(Lactobacillus johnsonii) CNCM I-1225、由BLIS Technologies有限公司(紐西蘭)以名稱KI2出售之唾液鏈球菌(Streptococcus salivarius) DSM 13084、尤其由Christian Hansen公司(丹麥)以商標Bb 12出售之乳酸雙歧桿菌(Bifidobacterium lactis) CNCM 1-3446、由Morinaga Milk Industry有限公司(日本)以商標BB536出售之長雙歧桿菌(Bifidobacterium longum) ATCC BAA-999、由Danisco以商標Bb-03出售之短雙歧桿菌(Bifidobacterium breve)、由Morinaga以商標M-16V出售之短雙歧桿菌、由Procter & GambIe公司以商標Bifantis出售之嬰兒雙歧桿菌(Bifidobacterium infantis)及由Institut Rosell(Lallemand)以商標R0070出售之短雙歧桿菌。
較佳地,本發明組合物以乾重計含有10e3 cfu至10e12 cfu、更佳10e7 cfu至10e12 cfu之益生菌菌株/g組合物。
本發明組合物可進一步包含至少一種益菌生,其量通常介於0.3重量%與10重量%組合物之間。
益菌生通常不在胃或小腸中分解並吸收,且因此其在進入結腸時保持完整,其在結腸中經有益細菌選擇性發酵,在此意義上,其係不可消化的。益菌生之實例包括某些寡醣,例如果寡醣(FOS)及半乳寡醣(GOS)。可使用益菌生之組合,例如90% GOS與10%短鏈果寡醣(例如BENEO-Orafti以商標「Orafti寡果醣」(參見https://www.beneo-orafti.com/Our-Products/Oligofructose)(先前係Raftilose)出售之產品中)或10%菊醣(例如BENEO-Orafti以商標「Orafti菊醣」(參見https://www.beneo-orafti.com/Our-Products/Inulin)(先前係Raftiline)出售之產品中)之組合。益菌生之尤佳組合係70%短鏈果寡醣及30%菊醣,其係由BENEO-Orafti以商標「Prebio 1」出售之產品。
本發明組合物可進一步包含其他營養化合物,該等其他營養化合物與所主張寡醣協同作用以遞送對皮膚(例如皮膚過敏或異位性皮膚炎)之所主張益處。該等其他化合物可係(例如)低致敏性蛋白質(即,水解或部分水解蛋白質)、低乳糖成份或低乳糖醣類。人們假定,可藉由以下事實確立成份之協同作用:各成份一起幫助維持效應物之低生理含量始終低於皮膚效應(例如異位性皮膚炎)開始顯示之閾值。
本發明組合物較佳係合成營養組合物。在此情形中,其可係初生嬰兒配方、嬰兒配方、幼兒食物、嬰兒穀類組合物、較大嬰兒配方或成長乳,且該組合物較佳係初生嬰兒配方。
根據較佳實施例,本發明組合物用於健康嬰兒及健康年幼兒童。
本發明組合物可在離乳期之前及/或期間使用。
因此,本發明組合物較佳用於降低異位性皮膚炎之頻率及/或發生率及/或嚴重性及/或持續時間及/或用於促進皮膚健康。
在一實施方案中,本發明組合物用於促進皮膚健康及/或用於預防皮膚脫水及/或用於增強皮膚水合及/或用於降低皮膚皮疹、粗糙及乾燥及/或用於增強對過敏原之口服耐受性。
本發明亦包括包含至少一種N-乙醯基乳糖胺、至少一種唾液酸基化寡醣及至少一種岩藻醣基化寡醣之組合物作為合成營養劑之用途,其用於預防及/或治療皮膚病況及皮膚疾病(較佳異位性皮膚炎)。
本發明亦包括包含至少一種N-乙醯基乳糖胺、至少一種唾液酸基化寡醣及至少一種岩藻醣基化寡醣之組合物作為合成營養劑之用途,其用於增強對過敏原之口服耐受性。
該等用途涵蓋組合物係較佳以單位劑量形式提供之補充品之情形。
上文所述所有用途尤其意欲用於嬰兒及年幼兒童。本發明之組合物及用途尤其適於具有過敏風險、具有家族過敏史或已經歷數次過敏(尤其係呼吸過敏或皮膚過敏)發作之嬰兒及兒童。在一實施例中,本發明之組合物及用途適合於具有過敏風險或已經歷過敏(尤其係呼吸過敏或皮膚過敏)發作之青少年或成人。
不希望受理論限制,本發明者認為,上文所述寡醣之組合在預防及/或治療皮膚病況及皮膚疾病(尤其異位性皮膚炎)中之效力可係由乳酸菌經由其刺激而誘發之黏膜免疫調節劑效應與特定寡醣摻合物之協同作用組合的結果。本發明者認為大多數具有最低發炎刺激之黏膜相關微生物叢之確立係藉由選擇性促進有益共生乳酸菌及同時調節諸如半乳糖凝集素(例如,半乳糖凝集素-1及半乳糖凝集素-3)等發炎調節劑來達成。此外,該組合物可調節內源性微生物叢之代謝,從而導致產生將有助於激活腸黏膜下面之免疫細胞之短鏈脂肪酸。誘發黏膜免疫系統之後,激活之免疫細胞、免疫活性化合物及/或免疫媒介物將循環至遠端位置(包括皮膚),其將在該等位置發揮免疫調節活性。總之,該等機制將有助於平衡潛在皮膚發炎病況,從而導致改善相關臨床表現(例如皮膚炎及濕疹)。另外,本發明者認為,該特別引發之免疫性可轉為降低對外源性刺激物之皮膚敏感性及增強皮膚障壁功能,從而降低與反應性皮膚相關之皮膚皮疹、粗糙及乾燥。
寡醣可在相同組合物中投與或可依序投與。
若欲用於0至12個月生命之年齡組,則組合物較佳係以液體形式食用之營養組合物。其可係營養完整配方,例如嬰兒配方、較大嬰兒配方或成長乳。對於年幼兒童組而言,另一選擇為,組合物可係(例如)汁液飲料或其他冷凍或常溫保存(shelf stable)飲品或湯,或幼兒食物或嬰兒穀類組合物。
本發明組合物亦含有蛋白質來源,其量較佳低於2.0 g/100 kcal,其量甚至更佳低於1.8 g/100 kcal。人們相信,蛋白質類型對本發明無關鍵作用,前提係滿足對於必需胺基酸之最基本要求且確保良好生長。因此,可使用基於乳清、酪蛋白及其混合物之蛋白質來源以及基於大豆之蛋白質來源。就乳清蛋白質而言,蛋白質來源可基於酸乳清或甜乳清或其混合物且可以任何期望比例包括α-乳白蛋白及β-乳球蛋白。
本發明組合物通常含有碳水化合物來源。此在本發明營養組合物係嬰兒配方之情形中尤佳。在此情形中,儘管較佳碳水化合物來源係乳糖,但仍可使用嬰兒配方中常用之任一碳水化合物來源,例如乳糖、蔗醣、麥芽糊精、澱粉及其混合物。
本發明組合物通常含有脂質來源。若本發明營養組合物係嬰兒配方,則此尤其適當。在此情形中,脂質來源可係適用於嬰兒配方之任一脂質或脂肪。較佳脂肪來源包括棕櫚油酸、高油酸向日葵油及高油酸紅花油。亦可添加必需脂肪酸亞麻油酸及α-次亞麻油酸,亦可添加少量含有大量預形成花生四烯酸及二十二碳六烯酸之油,例如魚油或微生物油。脂肪來源之n-6與n-3脂肪酸之比率較佳為約5:1至約15:1;例如約8:1至約10:1。
本發明組合物亦較佳以營養顯著量含有認為在日常飲食中所必需之所有維生素及礦物質。已確立對某些維生素及礦物之最基本要求。本發明組合物中視情況存在之礦物、維生素及其他營養素之實例包括維生素A、維生素B1、維生素B2、維生素B6、維生素B12、維生素E、維生素K、維生素C、維生素D、葉酸、肌醇、菸鹼酸、生物素、泛酸、膽鹼、鈣、磷、碘、鐵、鎂、銅、鋅、錳、氯、鉀、鈉、硒、鉻、鉬、牛磺酸及L-肉鹼。礦物通常以鹽形式添加。特定礦物及其他維生素之存在及量將視既定群體而變化。
若需要,則本發明組合物可含有乳化劑及穩定劑,例如大豆卵磷酯、單-及二甘油脂之檸檬酸酯及諸如此類。
本發明組合物亦可含有可能具有有益效應之其他物質,例如乳鐵蛋白、核苷酸、核苷及諸如此類。
現在藉助實例闡述本發明組合物。
配方可以任一適宜方式製備。例如,其可藉由以合適比例將蛋白質、碳水化合物來源及脂肪來源摻和在一起來製備。若使用,則乳化劑可於此時納入。維生素及礦物可於此時添加,但其通常在稍後添加以避免熱降解。可在摻和前將任何親脂性維生素、乳化劑及諸如此類溶解於脂肪來源中。然後可混入水(較佳為經過逆滲透之水)以形成液體混合物。水溫便利地在介於約50℃與約80℃之間之範圍內以幫助成份之分散。可使用市售液化劑來形成液體混合物。若欲使最後產物具有液體形式,則將於此階段添加N-乙醯基-乳糖胺、唾液酸基化寡醣及岩藻醣基化寡醣。若欲使最後產物為粉末,則若需要亦可在此階段添加該等寡醣。然後在(例如)兩個階段中將液體混合物均質化。
然後,可藉由(例如)將液體混合物迅速加熱至介於約80℃與約150℃之間之範圍內之溫度並保持介於約5秒與約5分鐘之間之持續時間,來熱處理液體混合物以降低細菌載量。此可藉助蒸汽注入、高壓釜或熱交換器(例如,板式熱交換器)來實施。
然後,可藉由(例如)急驟冷卻將液體混合物冷卻至介於約60℃與約85℃之間。然後,可在(例如)兩個階段中再次將液體混合物均質化,在第一階段中介於約10 Mpa與約30 Mpa之間,且在第二階段中介於約2 Mpa與約10 Mpa之間。然後,可進一步冷卻均質化混合物以添加任何熱敏感性組份,例如維生素及礦物質。宜在此時調整均質化混合物之pH及固體含量。
將均質化混合物轉移至適宜乾燥裝置(例如,噴霧乾燥器或冷凍乾燥器)中並轉化為粉末。粉末之水分含量應小於約5重量%。N-乙醯基-乳糖胺、唾液酸基化寡醣及岩藻醣基化寡醣可在此階段藉由與益生菌菌株(若使用)一起乾燥混合後添加,或由其以晶體糖漿形式與益生菌菌株(若使用)一起摻和並噴霧乾燥(或冷凍乾燥)後添加。
若液體組合物較佳,則可將均質化混合物滅菌然後無菌填充至適宜容器中,或可首先將其填充至容器中且然後經滅菌釜處理。
在另一實施例中,本發明組合物可係補充品,其以足以在個體中達成期望效應之量包括N-乙醯基-乳糖胺、唾液酸基化寡醣及岩藻醣基化寡醣。此投與形式更適於較年長兒童及成人。較佳地,N-乙醯基-乳糖胺之日劑量係0.1 g至3 g,唾液酸基化寡醣之日劑量係0.1 g至2 g,且岩藻醣基化寡醣之日劑量係0.1 g至3 g。
將根據欲投與補充品之方式來選擇欲包含於補充品中之寡醣之量。例如,若欲一天兩次投與補充品,則每份補充品可含有0.05 g至1.5 g之N-乙醯基-乳糖胺、0.05 g至1 g之唾液酸基化寡醣及0.05 g至1.5 g之岩藻醣基化寡醣。
補充品可呈(例如)錠劑、膠囊、軟錠或液體之形式。補充品可進一步含有保護性水膠體(例如膠、蛋白質、改質澱粉)、黏合劑、膜形成劑、囊封劑/材料、壁/殼材料、基質化合物、包衣、乳化劑、表面活性劑、增溶劑(油、脂肪、蠟、卵磷脂等)、吸附劑、載劑、填充劑、共化合物、分散劑、潤濕劑、處理助劑(溶劑)、流動劑、遮味劑、增重劑、膠凝劑(jellifying agent)及凝膠形成劑。補充品亦可含有習用醫藥添加劑及佐劑、賦形劑及稀釋劑,包括(但不限於)水、任何來源之明膠、植物膠、磺酸木質素、滑石、醣、澱粉、阿拉伯膠(gum arabic)、植物油、聚伸烷基二醇、矯味劑、防腐劑、穩定劑、乳化劑、緩衝劑、潤滑劑、著色劑、潤濕劑、填充劑及諸如此類。
另外,依照諸如USRDA等政府機構之推薦,補充品可含有適於口服或非經腸投與之有機或無機載劑材料以及維生素、痕量礦物元素及其他微量營養素。
本發明嬰兒配方之組合物之實例於下文給出。此組合物僅以說明方式給出。另一實例基於市售NAN及/或lactogen嬰兒配方(來自Nestl,瑞士),以下文所述量添加本發明特定寡醣。
下文概述之發現顯示,寡醣之特定摻合物促進諸如長雙歧桿菌嬰兒亞種(Bifidobacterium longum subsp infantis)等乳酸菌之代謝活性及生長。不希望受理論限制,此效應可部分解釋以下觀測結果:發現若剖腹產出生之兒童出現異位性過敏且尤其異位性濕疹直至2歲,則在其母親之早期乳中該等特定寡醣摻合物之量相對較低。此表明,根據本發明,提供具有安全量之特定寡醣摻合物之營養組合物可幫助重新確立嬰兒腸道中細菌之天然平衡及/或由此在預防及/或治療皮膚病況及皮膚疾病(較佳異位性皮膚炎)方面正面影響健康狀態。
使長雙歧桿菌嬰兒亞種(ATCC15697)在API生長培養基中厭氧生長,該API生長培養基補充有1%(w/v)葡萄糖或1%(w/v) 2'岩藻醣基乳糖(2FL)或1%(w/v)乳-N-新四醣(LNnT)或1%(w/v) 6'唾液酸基乳糖(6SL)或1%(w/v)之等量2FL、LNnT及6SL之組合。稀釋每一過夜培養物,以在含有0.1%葡萄糖作為碳源之DMEM(杜貝克氏改良伊氏培養基,Dulbeccos modified Eagle Medium)中具有0.1之起始OD600。所用此培養基不含任何其他碳水化合物補充品或具有額外之1%(w/v)葡萄糖或1%(w/v) 2'岩藻醣基乳糖(2FL)或1%(w/v)乳-N-新四醣(LNnT)或1%(w/v) 6'唾液酸基乳糖(6SL)或1%(w/v)之等量2FL、LNnT及6SL之組合。由此在37℃厭氧條件下調整DMEM培養基之條件。
再培育一夜之後,藉由在600 nm下量測OD來監測細菌之生長。然後使條件培養基離心且經由0.22微米過濾器過濾上清液以移除細菌。藉由HPLC使用Hi-Plex H管柱及UV檢測器來定量條件培養基中之乙酸鹽。
驚奇地發現,由等份之岩藻醣基化寡醣(例如,2'FL)、N-乙巰基化寡醣(例如,LNnT)及唾液酸基化寡醣(例如,6SL)組成之寡醣摻合物顯著提高乳酸菌(例如,雙歧桿菌)之代謝活性,如藉由乙酸鹽之形成可見(圖1)。
寡醣摻合物亦刺激該細菌之生長(圖2)。
圖1圖解說明實驗結果,其指示雙歧桿菌(長雙歧桿菌嬰兒亞種)在不含額外碳水化合物或具有以下額外物質之DMEM培養基中之代謝刺激:葡萄糖(Glc)或乳-N-新四醣(LNnT)或2'岩藻醣基乳糖(2FL)或6'唾液酸基乳糖(6SL)或LNnT、6SL及2FL之摻合物。(n=6;顯示帶有SEM之平均值;指明ANOVA顯著性(p<0.01))。
注意:僅LNnT、6SL及2FL之摻合物顯著刺激乙酸鹽之
產生。
圖2圖解說明實驗結果,其顯示雙歧桿菌(長雙歧桿菌嬰兒亞種)在不含額外碳水化合物或具有以下額外物質之培養基中之活體外生長:葡萄糖(Glc)或乳-N-新四醣(LNnT)或2'岩藻醣基乳糖(2FL)或6'唾液酸基乳糖(6SL)或LNnT、6SL及2FL之摻合物。(n=4;顯示帶有SEM之平均值;藉由小寫字母指明ANOVA顯著性(p<0.01))。
自約52個剖腹產出生之嬰兒母親對之隊列分析早期乳樣品中存在之特定寡醣之量。為此,將脫脂乳樣品在水中稀釋10倍至100倍,並藉由配備有CarboPac PA1管柱(Dionex)及電化學檢測器之HPAEC(Dionex)來分析。利用可靠寡醣標準品實施寡醣鑑別及量化。將嬰兒中(A)過敏疾病、(B)異位性過敏、(C)異位性濕疹之不存在或存在對由2FL、LNnT及6SL組成(圖3)或由2FL、LNnT、LNT(乳-N-四醣)、6SL及3SL(3'唾液酸基乳糖)組成(圖4)之寡醣摻合物之量作圖。
圖3圖解說明實驗結果,其顯示在剖腹產出生之兒童中直至2歲時(A)過敏疾病、(B)異位性過敏、(C)異位性濕疹之不存在(否)及發生(是)。對在母乳中量測之特定寡醣摻合物之量作圖。此處,代表之寡醣摻合物係2'岩藻醣基乳糖(2FL)、乳-N-新四醣(LNnT)及6'唾液酸基乳糖(6SL)之總和。(指明統計顯著性)
圖4圖解說明實驗結果,其顯示在剖腹產出生之兒童中直至2歲時(A)過敏疾病、(B)異位性過敏、(C)異位性濕疹之不存在(否)及發生(是)。對在母乳中量測之特定寡醣摻合物之量作圖。此處,代表之寡醣摻合物係2'岩藻醣基乳糖(2FL)、乳-N-新四醣(LNnT)、乳-N-四醣(LNT)、6'唾液酸基乳糖(6SL)及3'唾液酸基乳糖(3SL)之總和。(指明統計顯著性)
驚奇地發現,在兒童出現過敏疾病(圖3A、4A)時,早期乳中特定寡醣摻合物之含量傾向於相對較低。對於異位性疾病且尤其異位性濕疹,量測到若兒童直至2歲為止出現該等過敏,則其母親之早期乳中寡醣摻合物之含量顯著較低。
(無元件符號說明)
Claims (14)
- 一種組合物,其包含至少一種N-乙醯基-乳糖胺、至少一種唾液酸基化寡醣及至少一種岩藻醣基化寡醣,該組合物用於預防及/或治療皮膚病況及皮膚疾病,較佳係異位性皮膚炎。
- 如請求項1之組合物,其中該N-乙醯基-乳糖胺選自包含乳-N-四醣及乳-N-新四醣之群。
- 如請求項1之組合物,其中該唾液酸基化寡醣選自包含3'-唾液酸基乳糖及6'-唾液酸基乳糖之群,且該組合物較佳包含3'-唾液酸基乳糖及6'-唾液酸基乳糖二者,3'-唾液酸基乳糖與6'-唾液酸基乳糖之間之比率較佳在介於5:1與1:2之間之範圍內。
- 如請求項1之組合物,其中該岩藻醣基化寡醣選自包含以下之群:2'-岩藻醣基乳糖、3-岩藻醣基乳糖、二岩藻醣基乳糖、乳-N-岩藻五醣(換言之,乳-N-岩藻五醣I、乳-N-岩藻五醣II、乳-N-岩藻五醣III及乳-N-岩藻五醣V)、乳-N-二岩藻六醣I、岩藻醣基乳-N-六醣、二岩藻醣基乳-N-六醣I及二岩藻醣基乳-N-新六醣II,且該岩藻醣基化寡醣較佳係2'-岩藻醣基乳糖(2-FL)。
- 如請求項1至4中任一項之組合物,其中該組合物進一步包含至少一種益生菌菌株,該益生菌菌株較佳係雙歧桿菌(Bifidobacteria)及/或乳酸桿菌(Lactobacilli)。
- 如請求項1至4中任一項之組合物,其中該組合物進一步包含至少一種益菌生。
- 如請求項1至4中任一項之組合物,其中該組合物係初生嬰兒配方(starter infant formula)、嬰兒配方、較大嬰兒配方(follow-up formula)、幼兒食物配方、嬰兒穀類配方或成長乳,且該組合物較佳係初生嬰兒配方。
- 如請求項1至4中任一項之組合物,其用於健康嬰兒及健康年幼兒童。
- 如請求項1至4中任一項之組合物,其在離乳期之前及/或期間使用。
- 如請求項1至4中任一項之組合物,其用於預防該等皮膚疾病,具體而言異位性皮膚炎及降低其頻率及/或發生率及/或嚴重性及/或持續時間。
- 如請求項1至4中任一項之組合物,其用於促進皮膚健康及/或用於預防皮膚脫水及/或用於增強該皮膚之水合及/或用於降低皮膚皮疹、粗糙及/或乾燥及/或用於增強對過敏原之口服耐受性。
- 一種組合物之用途,該組合物包含至少一種N-乙醯基乳糖胺、至少一種唾液酸基化寡醣及至少一種岩藻醣基化寡醣,該組合物用於製造合成營養劑,該合成營養劑用於預防及/或治療皮膚病況及皮膚疾病,較佳係異位性皮膚炎。
- 一種組合物之用途,該組合物包含至少一種N-乙醯基乳糖胺、至少一種唾液酸基化寡醣及至少一種岩藻醣基化寡醣,該組合物用於製造合成營養劑,該合成營養劑用於增強對過敏原之口服耐受性。
- 如請求項12及13中任一項之用途,其中該組合物係較佳以單位劑量形式提供之補充品。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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EP10192227A EP2465507A1 (en) | 2010-11-23 | 2010-11-23 | Oligosaccharide composition for treating skin diseases |
PCT/EP2011/070561 WO2012076321A1 (en) | 2010-11-23 | 2011-11-21 | Oligosaccharide composition for treating skin diseases |
Publications (1)
Publication Number | Publication Date |
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TW201300111A true TW201300111A (zh) | 2013-01-01 |
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Family Applications (1)
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TW100142958A TW201300111A (zh) | 2010-11-23 | 2011-11-23 | 預防及/或治療皮膚病況及皮膚疾病之組合物 |
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US (1) | US8771674B2 (zh) |
EP (2) | EP2465507A1 (zh) |
CN (1) | CN104302297A (zh) |
AU (1) | AU2011340880B2 (zh) |
BR (1) | BR112013011730A2 (zh) |
CA (1) | CA2818011A1 (zh) |
CL (1) | CL2013001436A1 (zh) |
ES (1) | ES2616957T3 (zh) |
IL (1) | IL226049A0 (zh) |
MX (1) | MX341684B (zh) |
MY (1) | MY160894A (zh) |
PH (1) | PH12013500892A1 (zh) |
PL (1) | PL2643004T3 (zh) |
RU (1) | RU2609838C2 (zh) |
SG (1) | SG190079A1 (zh) |
TW (1) | TW201300111A (zh) |
WO (1) | WO2012076321A1 (zh) |
ZA (1) | ZA201304638B (zh) |
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CN105682664A (zh) | 2013-11-15 | 2016-06-15 | 雀巢产品技术援助有限公司 | 利用岩藻糖基化低聚糖预防或治疗非分泌型母亲诞下或喂养的婴儿的变态反应的组合物,尤其适用于有风险的婴儿或剖腹产婴儿 |
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US11096410B2 (en) * | 2016-01-26 | 2021-08-24 | Societe Des Produits Nestle S.A. | Composition for use in the prevention and/or treatment of skin conditions and skin diseases |
WO2017173241A1 (en) | 2016-03-31 | 2017-10-05 | Gojo Industries, Inc. | Sanitizer composition with probiotic/prebiotic active ingredient |
AU2017240068B2 (en) | 2016-03-31 | 2022-12-15 | Gojo Industries, Inc. | Antimicrobial peptide stimulating cleansing composition |
CA3043748A1 (en) | 2016-11-23 | 2018-05-31 | Gojo Industries, Inc. | Sanitizer composition with probiotic/prebiotic active ingredient |
WO2019038668A1 (en) | 2017-08-21 | 2019-02-28 | Glycom A/S | SYNTHETIC COMPOSITION TO REDUCE ALLERGY SYMPTOMS |
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2010
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- 2011-11-21 WO PCT/EP2011/070561 patent/WO2012076321A1/en active Application Filing
- 2011-11-21 BR BR112013011730A patent/BR112013011730A2/pt not_active IP Right Cessation
- 2011-11-21 CN CN201180056411.7A patent/CN104302297A/zh active Pending
- 2011-11-21 EP EP11784693.1A patent/EP2643004B1/en active Active
- 2011-11-21 AU AU2011340880A patent/AU2011340880B2/en active Active
- 2011-11-21 SG SG2013033345A patent/SG190079A1/en unknown
- 2011-11-21 MY MYPI2013700678A patent/MY160894A/en unknown
- 2011-11-21 CA CA2818011A patent/CA2818011A1/en not_active Abandoned
- 2011-11-21 US US13/988,990 patent/US8771674B2/en active Active
- 2011-11-21 ES ES11784693.1T patent/ES2616957T3/es active Active
- 2011-11-21 PL PL11784693T patent/PL2643004T3/pl unknown
- 2011-11-21 RU RU2013128594A patent/RU2609838C2/ru active
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- 2013-05-17 CL CL2013001436A patent/CL2013001436A1/es unknown
- 2013-06-21 ZA ZA2013/04638A patent/ZA201304638B/en unknown
Also Published As
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BR112013011730A2 (pt) | 2016-08-16 |
MY160894A (en) | 2017-03-31 |
CA2818011A1 (en) | 2012-06-14 |
IL226049A0 (en) | 2013-06-27 |
AU2011340880A1 (en) | 2013-05-23 |
ES2616957T3 (es) | 2017-06-14 |
CN104302297A (zh) | 2015-01-21 |
US8771674B2 (en) | 2014-07-08 |
WO2012076321A1 (en) | 2012-06-14 |
AU2011340880B2 (en) | 2017-03-02 |
US20130251682A1 (en) | 2013-09-26 |
MX2013005725A (es) | 2013-07-03 |
ZA201304638B (en) | 2016-02-24 |
EP2643004A1 (en) | 2013-10-02 |
RU2609838C2 (ru) | 2017-02-06 |
MX341684B (es) | 2016-08-30 |
CL2013001436A1 (es) | 2014-02-14 |
PH12013500892A1 (en) | 2013-07-01 |
EP2465507A1 (en) | 2012-06-20 |
EP2643004B1 (en) | 2016-12-21 |
SG190079A1 (en) | 2013-06-28 |
RU2013128594A (ru) | 2014-12-27 |
PL2643004T3 (pl) | 2017-07-31 |
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