CN1917779A - 用于改善皮肤状况和防止皮肤病的营养组合物 - Google Patents
用于改善皮肤状况和防止皮肤病的营养组合物 Download PDFInfo
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- CN1917779A CN1917779A CNA2005800042249A CN200580004224A CN1917779A CN 1917779 A CN1917779 A CN 1917779A CN A2005800042249 A CNA2005800042249 A CN A2005800042249A CN 200580004224 A CN200580004224 A CN 200580004224A CN 1917779 A CN1917779 A CN 1917779A
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Abstract
本发明涉及含有L-肉碱和至少一种具有抗氧化活性的组分的可摄入的组合物的用途,所述组合物用于刺激个体皮肤中的脂类代谢,这导致皮肤,特别是干燥、敏感或反应性皮肤的一般状况的改善,和防止发生皮肤病,诸如皮炎。此外,本发明还涉及此种组合物的用途,用于制备药物组合物或食物,特别是功能性食物或宠物食物,用于增加皮脂的脂类分泌,在皮肤上产生保护性皮脂层。
Description
本发明涉及含有L-肉碱和至少一种具有抗氧化活性的组分的用于刺激个体皮肤中的脂类代谢的可摄取的组合物的用途,所述刺激导致改善皮肤,特别是干燥、敏感的或反应性皮肤的状况,和防止发生皮肤病,如皮炎。本发明特别涉及此种组合物的用途,用于制备药物组合物或制备食物,特别是功能性食物。
皮肤是身体最大的器官并且作为对环境影响,诸如温度或身体支撑面的保护性屏障。皮肤也有助于调节体温、储存水分和脂肪和防止病原体进入身体。因为环境因素,诸如空气污染、或职业压力影响皮肤状况,所以我们工业社会中的日常生活对皮肤具有有害影响,所述有害影响最后导致皮肤状态和最终皮肤的性能恶化。
大体上,对于防止恶化或甚至改善皮肤状况和/或性能,已知两种方法。第一种方法在于直接在皮肤上涂抹局部剂型,诸如乳膏、软膏或洗剂,在特定条件下可以证明它们是有效的。然而,这些剂型存在缺点,即治疗的是皮肤的症状而不是导致皮肤恶化或者皮肤病的根本原因。
用于改善皮肤状况的第二种方法涉及施用设计用于在身体中作用的可摄入的组合物。本领域中已经提出了几种此类组合物,然而,所述组合物常常含有植物或动物来源的稀少而昂贵的原料。Jackson Laboratory(美国)报导降低饮食脂肪含量可以导致降低某些品系小鼠中特定皮肤病,诸如皮炎的发生率。然而,饮食中脂肪含量的降低仅仅延迟皮肤病并且不抑制溃疡性皮炎。此外,大部分这些组合物针对特定年龄的个体,例如青年个体或老龄人,或仅仅针对女人,且由于它们含有的成分,不适合用于长期消费。
考虑到现有技术的缺点,本发明的问题在于提供营养组合物,所述营养组合物可以用于长期消费,并通过改善皮肤状况和/或通过防止皮肤病而缓解所有个体,与他们的年龄和/或性别无关。
通过用含有L-肉碱和至少一种具有抗氧化活性的化合物的可摄入的组合物,刺激个体皮肤中的脂类代谢已经解决了这个问题。
在针对不同年龄个体的不同热量供给结果的深入研究工作期间,本发明人令人惊奇地注意到在施用的几种饮食中,一种饮食令人惊奇地刺激脂类代谢并因此提供了皮肤状况(例如,干燥、敏感或反应性皮肤)的保护作用,同时也有助于防止皮肤病,特别是溃疡性皮炎。基于这个发现,进行了随后的研究,导致鉴定了产生所观察到的作用的必需成分。
甚至更令人惊奇地,当给予相对富含脂肪的饮食时,可以观察到这个有益的作用,这与本领域中的通常理解是基本相反的,因为本领域中认为只能通过降低个体饮食中的脂肪含量才可以获得皮肤状况的显著改善。因为在西方社会的通常饮食中含有高含量的脂肪,所以这个特性似乎相当有利。
用可摄入组合物观察到的脂类代谢刺激活性可以与皮脂中的脂类增加一起进行。
这些作用导致皮肤状况的总体改善和防止皮肤病,诸如皮炎,特别是溃疡性皮炎、与糖尿病、循环紊乱、机械创伤、物理、化学或微生物损害(noxae)或湿疹相关的溃疡的发作/发生。可摄入的组合物也意在用于减轻搔痒。此外,当使用本组合物时,可以观察到个体皮肤状况的改善,所述个体的皮脂中脂类分泌降低,它是通常称为“干燥皮肤”或“敏感皮肤”的状况的几种病因之一。
本申请中所用的术语“可摄入的组合物”包含任意可用作食物的组合物。
术语“改善皮肤状况和防止皮肤病”不仅仅包含改善皮肤状况和防止皮肤病,也包含平衡皮肤中发生的过程。根据本发明的营养组合物刺激脂类代谢和特别地增加皮脂中的脂类分泌,且因此有助于在皮肤上产生保护性皮脂层。如公知地,皮脂是脂肪、细胞、游离酸的复杂混合物,所述混合物通过皮脂腺分泌并保护皮肤免受外部影响。不希望被任何理论束缚,因此可以假定为了增加皮脂中脂类分泌,不得不影响身体中多种不同和相互作用的代谢过程。
本申请中所用的术语“L-肉碱”包含天然存在的氨基酸L-肉碱,以及L-肉碱的酰基衍生物,例如L-肉碱的乙酰基衍生物或丙酰基L-肉碱。所述化合物可以从天然来源分离,或可以化学合成。优选的成分是天然存在的氨基酸L-肉碱。
术语“具有抗氧化活性的组分”或“抗氧化组分”包含具有抗氧化活性的任意可用作食物的组分,诸如维生素C、维生素E(生育酚和生育三烯酚(tocotrienoI)和其衍生物,诸如例如乙酸维生素E、类胡萝卜素(胡萝卜素、番茄红素、叶黄素、玉米黄质)、泛醌(例如CoQ10)、茶儿茶素(例如表儿茶素棓酸盐)、含有多酚和/或双萜(例如kawheol和咖啡醇)的咖啡提取物、银杏提取物、富含原花色素的葡萄或葡萄种子提取物、香料提取物(例如迷迭香)、含有异黄酮、植物雌激素的大豆提取物、上调细胞抗氧化防御的化合物(例如用于增加谷胱甘肽S-转移酶的熊去氧胆酸、用于增加过氧化氢酶的熊果酸、用于增加超氧化物歧化酶的人参和gingenoside和其天然来源,诸如草药)、为硫醇来源的化合物,例如硫辛酸、半胱氨酸、胱氨酸、甲硫氨酸、S-腺苷-甲硫氨酸、牛磺酸、谷胱甘肽、其天然来源,或上调它们的体内生物合成的化合物,以及抗氧化成分的混合物,诸如上述抗氧化成分的混合物。
每天向个体施用的L-肉碱的量是每天至少1mg/kg体重,优选每天1mg至1g/kg体重,更优选每天5mg至250mg/kg体重。特别对于人,可以选择L-肉碱的量为每天7至70mg/kg体重,特别是每天29至31mg/kg体重。对于宠物,诸如狗和猫,可以选择L-肉碱的量为每天21至210mg/kg体重,特别是每天19至21mg/kg体重。对于L-肉碱衍生物,对应的量基于化合物的分子量而变。
基本干燥形式中的人或哺乳动物食物的完全营养组合物可以包含例如达1800至2200ppm(百万分之一)的L-肉碱或其衍生物,更优选达750ppm的L-肉碱或其衍生物,最优选510至750ppm的L-肉碱或其衍生物。
包含例如每天至少0.025mg/kg体重,优选每天0.025mg至250mg/kg体重的抗氧化组分的营养组合物提供了良好结果。
抗氧化组分的组合的实例是例如维生素E(或其衍生物)与至少一种额外抗氧化组分,优选与维生素E相比具有较高水溶性的抗氧化组分的组合,诸如维生素E与至少一种,优选两种或三种抗氧化组分的组合,所述抗氧化组分选自维生素C或其衍生物、葡萄种子提取物和半胱氨酸。
在根据本发明的营养组合物中使用的维生素E或其衍生物的实例是例如通过商业途径可获得的乙酸α-生育酚酯,特别是(全外消旋)-构型。维生素E或所述衍生物可以以对应于AFFCO推荐的日剂量的2至6-倍,优选4.5至5.5-倍的量存在。
不希望被任何理论束缚,皮脂似乎是人面部皮肤中维生素E分泌的主要生理途径并且认为补充维生素E可以对脂类氧化,特别是皮脂中的脂类氧化起保护作用。
可以以维生素E的1至4倍的量,优选维生素E的1.5至3倍的量,更优选维生素E的1.7至2.3倍的量,最优选维生素E的2倍的量选择维生素C。在根据本发明的营养组合物中使用的维生素C或其衍生物的实例是例如通过商业途径可从Roche获得的稳定化维生素C。
用于根据本发明的营养组合物中的富含原花色素的葡萄或葡萄种子提取物的实例是包含儿茶素和鞣质的单体和聚合体的葡萄种子原花色素提取物(GSPE),其可以例如以名称Grapemax(Burgundy植物提取物)或Gravinol(Kikkoman)商业途径获得。Grapemax含有例如25%的儿茶素、45%的寡聚体(2至6聚体)和35%的鞣质。根据本发明的营养组合物中例如可以以每kg体重0.02至100mg的量,更优选每kg体重2.5至40mg的量包括GSPE作为日剂量。特别对于人,每kg体重2.5至10mg GSPE,特别对于宠物,例如猫和狗,每kg体重7.5至30mg可以用作日剂量。
这样的营养组合物提供了特别好的性质,该组合物中,L-肉碱和/或其酰基衍生物与抗氧化成分的摩尔比,即L-肉碱和/或其衍生物的量[mol])/抗氧化成分的量[mol]在2∶1至100∶1的范围,更优选在4∶1至50∶1的范围,最优选在5∶1至10∶1的范围。
本申请中所用的术语“脂肪来源”包含任何可用作食物的脂肪和/或油,不考虑它们在室温的稠度,即不考虑所述“脂肪来源”基本上以液体形式,例如大豆油,还是基本上以固体形式存在,例如动物脂。因此,在本发明的上下文中术语“脂肪”和“油”可以互换使用。文中所用的术语“不饱和脂肪酸”包含单不饱和脂肪酸,即具有一个C-C双键的脂肪酸,以及具有一个以上C-C双键的脂肪酸。
根据本发明的营养组合物可以包含动物和/或植物来源的脂肪。可以使用植物油,诸如玉米油、向日葵油、红花油、菜籽油、大豆油、橄榄油、琉璃苣油、黑醋栗种子油、花生油、米糠油和动物油,诸如动物脂,特别是牛油和鱼油。更优选地,脂肪来源可以包含不饱和脂肪酸,或富含包含不饱和脂肪酸的脂肪。脂肪来源(天然形式或富集后)可以包含至少30重量%的不饱和脂肪酸(包括作为甘油酯结合的不饱和脂肪酸、游离不饱和脂肪酸、或以任意其它形式结合的不饱和脂肪酸),每种脂肪酸都基于所述脂肪来源中存在的脂肪酸总含量。脂肪的来源也包含必需脂肪酸(亚油酸和α-亚油酸)和多不饱和脂肪酸,诸如γ-亚油酸、花生四烯酸、十二碳五烯酸和二十二碳六烯酸。
鱼油是十二碳五烯酸和二十二碳六烯酸的合适的来源,而琉璃苣油、黑醋栗种子油和报春花油是γ亚油酸的合适的来源。菜籽油、大豆油、亚麻子油和核桃油是α-亚油酸的合适的来源。红花油、向日葵油、玉米油和大豆油是亚油酸的合适的来源。橄榄油、菜籽油(芸苔)、高油酸向日葵和红花油、花生油、米糠油是单不饱和脂肪酸的合适的来源。
可以形成脂肪来源的基础并且可以用于制备根据本发明的营养组合物的优选的脂肪是动物脂,特别是牛油和大豆油。特别地,所述脂肪来源也可以包含属于n-3多不饱和脂肪酸,特别是α-亚麻酸家族的脂肪酸。不希望被任何理论束缚,例如认为α-亚麻酸是哺乳动物代谢中的前体物质,用于形成十二碳五烯酸、3系列的前列腺素和5系列的白三烯并且认为对人体和人皮肤提供有益作用。
在优选的实施方案中,如果用于制备根据本发明的营养组合物的脂肪来源是大豆油,那么该组合物可以包含例如至少1重量%,高达大约7重量%的n-3形式的脂肪酸。
有益地,所述n-3脂肪酸以(n-6脂肪酸)与(n-3脂肪酸)3∶1至10∶1,更优选4∶1至8∶1的重量比存在。如果需要,可以组合不同的动物或植物油以便获得脂肪来源的所希望的组合,例如可以将富含n-3脂肪酸的脂肪加入到脂肪或具有较低n-3脂肪酸含量的脂肪组合物中。
取决于意在用于营养组合物的剂型,脂肪含量可以不同。对于意在提供完全膳食或点心的营养配方或对于与具有相对低的脂肪含量的膳食一起消费的营养补充物,营养组合物可以包含基于营养组合物总重量高达40重量%,优选6至25重量%,更优选10至12重量%的脂肪来源。对于意在用于与具有相对高脂肪含量的营养物一起消费的营养补充物,营养组合物可以包含基于营养组合物总重量至少0.5重量%的所述脂肪来源。
根据本发明的营养组合物还可以补充可用作食物的糖类来源和/或蛋白质、氨基酸和/或肽来源。例如,糖类来源可以是例如稻、大麦、高梁、栗、燕麦、玉米的面粉、谷粒或淀粉。也可以用糖,特别是二糖和寡糖,例如蔗糖、葡萄糖和玉米糖浆。此外也可以加入适当的纤维。如需要,可以选择糖类来源提供的糖类的量。例如,食物可以含有基于营养组合物总重量高达大约65重量%的糖类,更优选45至60%重量的糖类。
用于根据本发明的营养组合物的合适的蛋白质来源可以选自任意合适的动物或植物蛋白质来源,例如,肌肉或骨骼肉、肉和骨粉、家禽粉、鱼粉、乳蛋白质、玉米谷蛋白、小麦谷蛋白、大豆粉、大豆蛋白质浓缩物、大豆蛋白质分离物、卵蛋白、膳食蛋白质,诸如,乳清、酪蛋白、谷蛋白,等等。如需要,可以选择蛋白质、肽和氨基酸(不考虑L-肉碱的量)的量。例如,营养组合物可以含有基于总组合物干重大约12重量%至大约70重量%的蛋白质。
糖类、蛋白质、肽、氨基酸来源的选择可以基于它的消费者的营养需要、适口性考虑、和生产的产品类型进行选择。此外,如需要,可以将多种其它成分,例如,盐、香料、调味品、维生素、矿物质、调味剂、树胶、益生素和益生微生物掺入到营养组合物中。
可以以任意合适的形式提供益生素。例如,可以以含有益生素的植物材料的形式提供益生素。合适的植物材料是例如芦笋、朝鲜蓟、洋葱、小麦、雪莲果(yacon)或菊苣,或这些植物材料的残留物。备选地,益生素可以作为通常称为果寡糖、半乳寡糖、木寡糖的菊粉提取物或它的水解产物或作为淀粉寡糖衍生物来提供。来自菊苣的提取物是特别合适的。营养组合物中益生素的最高水平优选大约为按重量计约20%,特别按重量计约10%。例如,益生素可以占营养组合物重量的大约0.1%至大约5%。对于用菊苣作为益生素的营养组合物,菊苣可以占营养组合物的大约0.5重量%至大约10重量%,更优选大约1重量%至大约5重量%,每个百分数都基于总组合物的干重。
益生微生物可以选自合适用于人消费和/或哺乳动物消费并且能改善肠中微生物平衡的一种或多种微生物。合适的益生微生物的实例包括酵母,如酵母属(Saccharomyces)、德巴利酵母属(Debaromyces)、假丝酵母属(Candida)、毕赤酵母属(Pichia)和球拟酵母属(Torulopsis),霉菌,如曲霉属(Aspergillus)、根霉属(Rhizopus)、毛霉属(Mucor)和青霉属(Penicillium)和球拟酵母属,和细菌,如双歧杆菌属(Bifidobacterium)、拟杆菌属(Bacteroides)、梭状芽孢杆菌属(Clostridium)、梭形杆菌属(Fusobacterium)、Melissococcus、丙酸菌属(Propioni-bacterium)、链球菌属(Streptococcus)、肠球菌属(Enterococcus)、乳球菌属(Lactococcus)、葡萄球菌属(Staphylococcus)、消化链球菌属(Peptostrepococcus)、芽孢杆菌属(Bacillus)、片球菌属(Pediococcus)、微球菌属(Micrococcus)、明串珠菌属(Leuconostoc)、Weissella、气球菌属(Aerococcus)、Oenococcus和乳杆菌属(Lactobacillus)。合适的益生微生物的特定实例是:酿酒酵母(Saccharomyces cereviseae)、凝结芽孢杆菌(Bacillus coagulans)、地衣芽孢杆菌(Bacillus licheniformis)、枯草芽孢杆菌(Bacillus subtilis)、Bifdobacterium bifidum、婴儿双歧杆菌(Bifidobacterium infantis)、长双歧杆菌(Bifidobacterium longum)、屎肠球菌(Enterococcus faecium)、粪肠球菌(Enterococcus faecalis)、嗜酸乳杆菌(Lactobacillus acidophilus)、食品乳杆菌(Lactobacillus alimentarius)、干酪乳杆菌干酪亚种(Lactobacillus caseisubsp.casei)、Latobacillus casei Shirota、弯曲乳杆菌(Lactobacilluscurvatus)、德氏乳杆菌乳酸亚种(Lactobacillus delbruckii subsp.Lactis)、Lactobacillus farciminus、加氏乳杆菌(Lactobacillus gasseri)、瑞士乳杆菌(Lactobacillus helveticus)、约氏乳杆菌(Lactobacillus johnsonii)、罗伊乳杆菌(Lactobacillus reuteri)、鼠李糖乳杆菌(Lactobacillus rhamnosus)(乳杆菌GG)、清酒乳杆菌(Lactobacillus sake)、乳酸乳球菌(Lactococcus lactis)、变异微球菌(Micrococcus varians)、乳酸片球菌(Pediococcus acidilactici)、戊糖片球菌(Pediococcus pentosaceus)、乳酸片球菌(Pediococcusacidilactici)、嗜盐片球菌(Pediococcus halophilus)、粪链球菌(Streptococcusfaecalis)、嗜热链球菌(Streptococcus thermophilus)、肉葡萄球菌(Staphylococcus carnosus)和木糖葡萄球菌(Staphylococcus xylosus)。
益生微生物可以是粉状、干燥形式,特别对于形成芽孢的微生物,可以是芽孢形式。此外,如果需要,益生微生物可以例如,在糖基质、脂肪基质或多糖基质中包胶以额外增加存活的可能性。如果使用益生微生物,营养组合物优选每克营养组合物含有约104至约1010个益生微生物细胞,更优选每克含有约106至108个益生微生物细胞。营养组合物可以含有约0.5重量%至约20重量%的益生微生物混合物,优选约1重量%至约6重量%,例如约3重量%至约6重量%的益生微生物混合物,每个重量%都基于总组合物的干重。
如果需要,可以将一种或多种食品级乳化剂,例如甘油一酯和甘油二酯的二乙酰基酒石酸酯、卵磷脂和甘油一酯和甘油二酯掺入到营养组合物中。类似地,可以包括合适的盐和稳定剂。
营养组合物可以用于人和/或哺乳动物,特别是宠物,诸如猫和狗,并且将适合于各自目标哺乳动物的特定营养需要。
所述组合物可以作为正常饮食的补充物或作为营养完全食物的组分向各自个体施用。食物组合物也可以是完全的和营养平衡的食物。
在一个实施方案中,可以制备营养完全的食物或宠物食物。营养完全的食物或宠物食物可以是任意合适的形式,例如干燥形式、半湿润形式或湿润形式,它可以是冷冻或耐储存的宠物食品。这些食物或宠物食物可以按常规方式生产。除了根据本发明的营养组合物外,这些食物或宠物食物包括糖类来源,蛋白质来源和脂类来源的任意一种或多种。
对于干燥食物或干燥宠物食物,虽然可以用烘焙和其它合适的方法,但是合适的方法是挤压烹饪。当挤压烹饪宠物食物时,干燥的宠物食物一般以粗粒食物的形式提供。如果用益生素,在加工前可以将益生素与干燥食物或宠物食物的其它成分预混和。在EP-A-0850569中描述了合适的方法。如果使用益生微生物,该生物最好涂布在干宠物食物上或填充在干宠物食物中。EP-A-0862863中描述了合适的方法。
对于湿润食物或湿润宠物食物,可以使用US-4,781,939和US-5,132,137中描述的方法生产模拟的肉产品。也可以使用用于产生块型产品的其它方法,例如在蒸气烤箱中烹饪。备选地,可以生产条型产品,将合适的肉材料乳化以产生肉乳液、加入合适的胶凝剂并加热该肉乳液后填充罐头或其它容器来生产条型产品。
用于人消费的营养组合物可以是例如营养完全配方、乳制品、冷冻或耐储存的饮料、汤、饮食添加物、膳食替代物和营养条或糕饼。
营养组合物可以例如以粉剂、液体浓缩物或即饮饮料的形式经肠施用。如果需要产生粉状营养配方,将匀浆化的混合物转移到合适的干燥装置诸如喷雾干燥器或冷冻干燥器并转化成粉末。
除此之外,也可以用根据本发明的营养组合物丰富一般食品,例如发酵乳、酸乳酪、新鲜乳酪、凝乳(renneted milk)、糕饼条、早餐谷物片或谷物条、饮料、奶粉、基于大豆的产品、非发酵乳制品或用于临床营养的营养补充物。
优选地,通过人和/或哺乳动物消耗以获得有益作用的食物组合物的量将取决于它的大小、它的类型和它的年龄并且可以通过本领域技术人员根据技术中常识选择。
由于根据本发明的营养组合物提供对皮肤的有益作用而不需要限制饮食的脂肪含量,可以预计它将很受消费者欢迎。因此,本发明克服了本领域中存在的偏见,如以前认为只能在相对低脂肪的基础上实现此类效果。
应当理解根据本发明的营养组合物的组分在本文中提供了超过和/或不同于单独使用时各自组分的协同活性。
以下实施例仅用于阐明给出并不应理解为限制本申请的主题。除非另外说明,给出的所有百分数都是按重量计的。它们前面是附图简述。
图1显示了喂食如实施例1描述的饮食A至E和喂食饮食F的雄性小鼠C57BL/6J上通过HPLC测定的毛皮脂脂类的量。将皮脂脂类分为3类:胆固醇+甘油二酯、甘油三酯,和胆固醇和蜡酯。
实施例1
鼠模型中的观察
研究设计和饮食
自Iffa credo(法国)获得9周龄雄性小鼠C57BL/6J。到达后将小鼠分组饲养,每组6只动物。适应3周后,将小鼠(12周龄)随机分为5组(A至E),每组12只并分开饲养。小鼠自由饮水并进行12小时光照和黑暗循环。
成年小鼠中的饮食干预是从12至15月龄的3个月的喂食。
老年小鼠的饮食干预是21至24个月的喂食或长期喂食21个月以上(从3至24月龄)。
除了热量受限制的小鼠组外,所有动物组都自由喂食,对所述热量受限制的小鼠喂食对照自由喂食组消耗的每日食物的67%。每周测量动物体重一次。
将由18%的蛋白质(大豆和乳清)、11%的脂肪(大豆油)、59%的糖类(淀粉+蔗糖)和10%的纤维素组成的对照饮食(饮食A)补充含有维生素C、维生素E、葡萄种子提取物和半胱氨酸的抗氧化剂混合物(饮食C)和/或L-肉碱(分别是饮食D和E)。对于热量限制(饮食B),将脂肪、淀粉和蔗糖降低以提供自由喂食对照组消费的每日热量的67%,而提供100%的蛋白质、矿物质和维生素。这些饮食如下:
饮食A-对照:18%的蛋白质(大豆和乳清)、11%的脂肪、59%的糖类、5%的纤维素;
饮食AL-对照:长期施用饮食A24个月以上;
饮食B-热量限制:18%的蛋白质(大豆和乳清)、7.7%的脂肪、32.5%的糖类、5%的纤维素;
饮食BL-对照:长期施用饮食B24个月以上;
饮食C-抗氧化剂混合物:饮食A+0.19%的维生素C、0.03%的维生素E、0.075%的葡萄种子提取物、0.4%的半胱氨酸;
饮食D:饮食A+0.3%的L-肉碱+饮食C的抗氧化剂混合物;
饮食DL-对照:长期施用饮食D24个月以上;
饮食E:饮食A+0.3%的L-肉碱;
饮食F:饮食A+0.3%的L-肉碱。
如以上谈及地,如本发明中描述的研究最初是针对确定热量限制对小鼠死亡率的影响,为此向动物施用饮食B。
注意到比较饮食之一-饮食D-对于炎性皮肤病有保护活性并且有助于避免皮炎,特别是溃疡性皮炎,和增加皮脂中脂类的分泌。
C57BL/6J中的溃疡性皮炎
过度理毛行为、脱毛症和皮炎是近交C57BL/6J小鼠的特征并且可以在早至2-4月龄时发生。下表1显示了在多种饮食组中皮炎的发生率。
表1
组 | 病例数 | 组大小 | 发生率 | 时期 |
A | 2 | 20 | 0.10 | 21-24个月 |
B | 2 | 19 | 0.11 | 21-24个月 |
C | 3 | 19 | 0.16 | 21-24个月 |
D | 0 | 19 | 0.00 | 21-24个月 |
E | 3 | 19 | 0.16 | 21-24个月 |
AL | 10 | 30 | 0.33 | 24个月以上 |
DL | 3 | 30 | 0.10 | 24个月以上 |
BL | 2 | 24 | 0.08 | 24个月以上 |
接受包含根据本发明的组合物的饮食(饮食D)的小鼠的皮炎发生率显著低于其它饮食组。
属于对照组(AL组)的许多小鼠在中年(12至18月龄)发生溃疡性皮炎,所述溃疡性皮炎导致大范围皮肤损伤、皮肤感染和显著的体重减轻。特别地,由于皮肤紊乱,对照饮食的小鼠经历了高死亡发生率。
喂食对照饮食的小鼠比属于其它饮食组的小鼠更易患皮肤病。在研究结束时,观察到DL和BL组中很少的皮肤损伤(BL2例,DL2例)。因此,热量限制饮食(B、BL)和饮食D(DL、D)显示出具有保护作用。
此外,本研究中注意到对照组A的小鼠在12月龄时发生皮炎,即晚于Jackson Laboratory(美国)以前报导的。因此,对照饮食自身似乎提供了保护因子,并且进一步的研究表明该保护因子是研究期间施用的大豆油中的相对高含量的α-亚麻酸。表2显示了与玉米油相比大豆油中α-亚麻酸和亚油酸的含量。
表2
饮食中存在的必需脂肪酸(FA)(总FA的%) | ||
亚油酸(LA)18:2 n=6 | α-亚麻酸(ALA)18:3 n=3 | |
玉米油 | 57 | 0.9 |
大豆油 | 53 | 7 |
当用包含L-肉碱和以下抗氧化剂:维生素C、维生素E、葡萄种子提取物和半胱氨酸的两种的饮食时,对于刺激脂类代谢,也得到优于标准饮食的结果。
实施例2:成年和老年小鼠中毛皮脂脂类的测定
通过HPLC测定喂食如实施例1中描述的饮食A、B、C、D和E的实施例1的小鼠C57BL/6J的毛皮脂脂类。将皮脂脂类分为3类:(1)极性脂类:甘油二酯、脂肪酸和胆固醇(2)甘油三酯和(3)非极性脂类:胆固醇和蜡酯。
成年小鼠(15月龄)中毛皮脂脂类的测定
表3和4中代表的结果显示了在喂食饮食D的成年小鼠中,毛皮脂总脂类量、非极性脂类(胆固醇和蜡酯)和极性脂类(甘油二酯脂肪酸和胆固醇)增加(表3,灰框)。然而在饮食D中脂类平衡没有显著改变(表4,白框)。相反地,喂食热量限制的小鼠在皮脂中总脂类以及非极性脂类和甘油三酯的量显著减少(表3,灰框)。此外,在热量限制小鼠中脂类平衡改变(表4,白框),甘油三酯比例降低并且极性脂类比例增加。
表3
μg脂类/mg毛-15月龄小鼠 | ||||||||
胆固醇/蜡酯(非极性脂类) | 甘油三酯 | 胆固醇/甘油二酯/FA(极性脂类) | 总的脂类 | |||||
平均值 | sem | 平均值 | sem | 平均值 | sem | 平均值 | sem | |
A | 6.73 | 0.51 | 3.07 | 0.74 | 2.45 | 0.12 | 12.26 | 1.11 |
BCDE | 4.897.649.206.58 | 0.620.600.760.31 | 0.723.013.842.10 | 0.120.810.570.33 | 2.683.113.502.34 | 0.240.210.300.10 | 8.2313.7616.5411.02 | 0.831.421.260.54 |
喂食如实施例1中不同饮食的成年小鼠的皮脂中总脂类的量(灰框)和脂类平衡(白框)。
值表示为每毫克毛的微克脂类。
表4
用双侧斯氏t检验对A的统计学分析 | ||||||||
胆固醇和蜡酯 | 甘油三酯 | 胆固醇/甘油二酯/FA | 总的脂类 | |||||
P值 | P值 | P值 | P值 | |||||
A | ||||||||
BCDE | 0.03700.26740.01480.7881 | *NS*NS | 0.00370.95890.41760.2145 | **NSNSNS | 0.44030.01610.00500.4647 | NS***NS | 0.00760.42180.02030.3006 | **NS*NS |
成年小鼠毛皮脂的总脂类和脂类平衡的统计学分析。
显著不同于对照的值通过*标记,p<0.05。NS=无显著性。
老年(24个月)小鼠中毛皮脂脂类的测定
表5和6表示如实施例1中谈及的对于老年小鼠的饮食补充物的结果。与显示总毛皮脂脂类降低的热量受限制的小鼠相反,来自喂食饮食C、D和E的小鼠的总脂类毛皮脂量显著增加。饮食B、BL、C和D中以相似方式改变脂类平衡,胆固醇和蜡酯比例增加和胆固醇、甘油二酯和脂肪酸脂类比例降低。此外,如在成年小鼠中看到地,短期热量限制显示出甘油三酯降低。
表5
μg脂类/mg毛 | |||||||
胆固醇和蜡酯 | 甘油三酯 | 胆固醇/甘油二酯/FA | 总的 | ||||
平均值 | sem | 平均值 | sem | 平均值 | sem | 平均值 | sem |
ABCDEBLDL | 5.096.5812.0310.089.816.3011.13 | 0.820.620.881.070.720.531.09 | 3.211.325.383.495.811.175.66 | 0.810.361.450.870.950.280.90 | 2.251.462.622.432.372.502.96 | 0.150.140.060.160.060.080.17 | 10.559.3620.0316.0017.999.9619.74 | 1.310.872.051.821.330.711.91 |
24月龄小鼠的毛皮脂脂类量(灰框)和脂类平衡(白框)。BL和DL表示分别
用饮食B和D长期喂食小鼠。
表6
用双侧斯氏t检验进行的统计学分析 | ||||||||
胆固醇和蜡酯 | 甘油三酯 | 胆固醇/甘油二酯/FA | 总的 | |||||
P值 | P值 | P值 | P值 | |||||
A | ||||||||
BCDEBLDL | 0.16640.00000.00190.00050.23270.0004 | NS********NS*** | 0.04900.20920.81570.05380.02970.0596 | *NSNSNS*NS | 0.00130.03570.42200.47810.16390.0065 | ***NSNSNS** | 0.46100.00130.02710.00110.69910.0011 | NS*****NS** |
老年小鼠毛皮脂的总脂类和脂肪平衡的统计学分析。
值显著不同于对照值*p<0.05,**p<0.01,***p<0.001,NS=无显著性。
Claims (15)
1.L-肉碱和具有抗氧化活性的至少一种组分用于制备用于刺激动物或人皮肤中的脂类代谢的可摄入组合物的用途。
2.根据权利要求1的用途,用于增加皮脂中的脂类分泌。
3.根据权利要求2的用途,用于在皮肤上产生保护性皮脂层。
4.根据权利要求1至3之一的用途,用于治疗皮炎。
5.根据权利要求4的用途,用于治疗溃疡性皮炎。
6.根据权利要求1至3之一的用途,用于减轻干燥皮肤或搔痒。
7.根据前面权利要求任一项的用途,其中显示出抗氧化活性的组分选自维生素E;维生素C;类胡萝卜素;泛醌;茶儿茶素;含有多酚和/或二萜的咖啡提取物;银杏提取物;富含原花色素的葡萄或葡萄种子提取物;香料提取物;含有异黄酮、植物雌激素的大豆提取物;熊去氧胆酸;熊果酸;人参和gingenoside和其天然来源;硫醇来源,优选硫辛酸、半胱氨酸、胱氨酸、甲硫氨酸、S-腺苷-甲硫氨酸、牛磺酸、谷胱甘肽或其天然来源;或其混合物。
8.根据前面权利要求任一项的用途,其中每天施用的L-肉碱的量为1mg至1g/kg体重/天,优选5mg至250mg/kg体重/天。
9.根据前面权利要求任一项的用途,其中具有抗氧化活性的组分的量为0.025mg至250mg/kg体重/天。
10.根据前面权利要求任一项的用途,其中可摄入的组合物含有脂肪来源,其包含不饱和脂肪酸或富含不饱和脂肪酸。
11.根据权利要求10的用途,其中不饱和脂肪酸是α-亚麻酸。
12.根据权利要求10或11中任意一项的用途,其中所述脂肪来源选自动物脂肪,优选动物脂或鱼油,更优选牛油,或植物脂肪,优选玉米油、向日葵油、红花油、菜籽油、大豆油、橄榄油、琉璃苣油、黑醋栗种子油。
13.根据权利要求10至12中任意一项的用途,其中组合物中所述脂肪来源的量基于组合物的总重量按重量计为至少0.1%。
14.根据前面权利要求任意一项的用途,其中可摄入的组合物是药物、食物或功能性食物、营养完全的宠物或人类食物或饮食补充物。
15.可摄入的组合物,其选自包含L-肉碱和至少一种具有抗氧化活性的组分的药物、食物、功能性食物、营养完全的宠物或人类食物和膳食。
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Cited By (7)
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CN103282013A (zh) * | 2010-10-27 | 2013-09-04 | 雀巢产品技术援助有限公司 | 适合用于促进健康的皮肤的方法和组合物 |
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CN108208602A (zh) * | 2017-11-29 | 2018-06-29 | 兰溪市哥特生物技术有限公司 | 含有从毛蚶中提取的活性多肽的保健品制备方法 |
CN114096155A (zh) * | 2019-07-02 | 2022-02-25 | 马斯公司 | 动物食物组合物 |
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