CN1777420A - 用于预防和/或改善与生活方式相关疾病的经加工的油脂组合物 - Google Patents
用于预防和/或改善与生活方式相关疾病的经加工的油脂组合物 Download PDFInfo
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- CN1777420A CN1777420A CNA2004800102175A CN200480010217A CN1777420A CN 1777420 A CN1777420 A CN 1777420A CN A2004800102175 A CNA2004800102175 A CN A2004800102175A CN 200480010217 A CN200480010217 A CN 200480010217A CN 1777420 A CN1777420 A CN 1777420A
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- glabridin
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- methyl
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Abstract
本发明的目的在于提供一种用于预防和/或改善与生活方式相关疾病的组合物,其包含至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物,这些化合物具有PPARγ配体活性,并可有效地改善胰岛素耐受性以及预防和/或改善与生活方式相关疾病比如内脏脂肪肥胖症、II型糖尿病、高脂血症和高血压,其可用于食物和饮料(比如保健食物和保健功能食物)、药物、非药物、化妆品等;或提供一种用于抑制和/或改善体重增加的组合物。
Description
技术领域
本发明涉及一种用于预防和/或改善与生活方式相关疾病的经加工的油脂组合物(fat and oil processed composition)(经加工的油脂组合物或经加工的包含油类和脂类的组合物),和/或用于抑制和/或改善体重增加的经加工的油脂组合物,其可用于食物和饮料比如保健食品、具有保健要求的食物(用于特定用途[FOSHU]的食物和具有营养功能要求的食物)、医药、非医药、化妆品等。
背景领域
最近几年中,由于日常生活环境恶化比如饮食习惯的西化和缺乏运动,肥胖症的人数不断增加,伴随肥胖症增加的与生活方式相关疾病已被认为是严重的社会问题。与生活方式相关疾病包括内脏的脂肪肥胖症(visceral fatobesity)、II型糖尿病、高脂血症以及高血压,这些疾病属于多危险因素综合征并最终引起血管疾病比如动脉硬化。因此,需要对由肥胖症所引起的体重增加具有抑制作用的组合物,以预防和/或改善这些与生活方式相关疾病,作为该组合物的形式需要是可每日摄取的食物和饮料比如保健食品和具有保健要求的食物(用于特定用途[FOSHU]和具有营养功能要求的食物)、或医药、非医药、化妆品等。
多危险因素综合征被认为是“代谢性综合征”,与根据Reaven的“综合征X”(Diabetes,37,1595-1607,1988)、根据Kaplan的“致命四重奏(the deathlyquartet)”(Archives of Internal Medicine,149,1514-1520,1989)、根据DeFronzo的“胰岛素耐受性综合征”(Diabetes Care,14,173-194,1991)以及根据Matsuzawa的“内脏脂肪综合征”(Diabetes/Metabolism Reviews,13,3-13,1997)是相同的病理概念,且据估计这些综合征中共同的至病因素是胰岛素耐受性。
已显示用于改善胰岛素耐受性的药物噻唑烷衍生物比如曲格列酮、匹格列酮和罗格列酮,起核内受体过氧化物酶体增殖剂-激活受体γ(PPARγ)的配体的作用,改善II型糖尿病患者的胰岛素耐受性,并且表现出降低血糖增高药的作用。还显示这些噻唑烷衍生物增加皮下脂肪量但降低内脏脂肪量并表现出降低血液游离脂肪酸作用、降低血压作用和抗炎作用(参见Martens,F.M.,et al.,Drugs,62,1463-1480,2002)。也就是说,那些具有PPARγ配体活性的化合物可有效改善胰岛素耐受性并预防和/或改善与生活方式相关疾病比如内脏脂肪肥胖症、II型糖尿病、高脂血和高血压。
甘草是一种豆科甘草属(Glycyrrhiza)植物,用作食物和药物(草药),其主要的种属包括光果甘草(Glycyrrhiza glabra)、甘草(G.uralensis),胀果甘草(G.inflata)等。亲水性组分甘草甜素(甘草酸)包含于任何种属的甘草中,而疏水性组分黄酮类化合物则作为特定化合物包含于特定种属中。有时利用这些种属特异性黄酮类化合物识别甘草种属。
在从甘草获得的萃取物中,发现疏水性甘草萃取物可用于预防和/或改善的多危险因素综合征,其中所述疏水性甘草萃取物包含大量甘草黄酮类化合物和很少量甘草甜素(参见WO 02/47699)。
另一方面,包含于疏水性甘草萃取物的疏水性甘草黄酮类化合物几乎不溶于水,当为有机溶剂萃取物的形式时容易硬化,随时间变化快速发生颜色的显著改变,因此难以被应用。为了解决这一问题,将疏水性甘草黄酮类化合物溶于中链脂肪酸甘油三酯中,并将所得疏水性甘草黄酮类化合物制剂用作抗氧化剂、抗菌剂、酶抑制剂、着色剂、抗肿瘤剂、抗变应性剂(anti-allergic agent)和抗病毒剂(参见日本专利号2794433)。但是在日本专利号2794433中并不限于该化合物,并且不知它们用作预防和/或改善与生活方式相关疾病的药物以及它们对抑制和/或改善体重增加的作用。
本发明所要解决的问题
综上,光甘草素(glabrene)、光甘草定(glabridin)、光甘草酚(glabrol)、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B(hyspaglabridin B)具有PPARγ配体活性,并由此在改善胰岛素耐受性中和在预防和/或改善与生活方式相关疾病比如内脏脂肪肥胖症、II型糖尿病、高脂血和高血压中有效。但是,这些化合物的水溶性和稳定性较差,因此难以应用于饮食品和医药。因此,本发明提供了用于预防和/或改善与生活方式相关疾病的组合物,和/或抑制和/或改善体重增加的组合物,其包含至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物,其可用于饮食品中比如保健食物、具有保健要求的食物(用于特定用途[FOSHU]和具有营养功能要求的食物)、或医药、非医药或化妆品等。
发明内容
本发明人鉴于上述情况进行了彻底研究,并因而发现光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定、和欧甘草素B或其盐、酯或糖苷特别溶解于某些种类的油脂中由此改善了这些化合物的稳定性,还改善了其加工成饮食品、医药、非医药、化妆品等的可加工性,并且表现出抑制营养过剩时体重增加的作用,由此完成了本发明。
即,本发明的第一方面涉及用于预防和/或改善与生活方式相关疾病的经加工的油脂组合物,其包含其中溶解有至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定、和欧甘草素B的化合物或其盐、酯或糖苷的油脂,本发明第二方面涉及用于抑制和/或改善体重增加的经加工的油脂组合物,其包含其中溶解有至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定、和欧甘草素B的化合物或其盐、酯或糖苷的油脂。
本发明的最佳实施方式
在下文,参考其实施方案对本发明进行了详细描述。
根据本发明的用于预防和/或改善与生活方式相关疾病的经加工的油脂组合物,和用于抑制和/或改善体重增加的经加工的油脂组合物,包含其中溶解有至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物或其盐、酯或糖苷的油脂。如此处所用,经加工的油脂组合物是其中溶解有上述化合物的油脂或用于饮食品、医药、非医药、化妆品等包含该油脂的组合物。即,经加工的油脂组合物包括油脂中溶解有上述化合物的组合物、包含其它物质与上述组合物混合的组合物、以及用于饮食品、医药、非医药、化妆品等的组合物,其通过加工上述组合物而制备。优选地,该组合物包含光甘草定和至少一种选自光甘草素、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物。该组合物更优选包含光甘草定、光甘草素以及至少一种选自光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物。该组合物最优选包含全部的光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B。这些化合物的总量优选约为基于该经加工的油脂组合物的0.01至30重量%,更优选约0.1至30重量%,更加优选约1至10重量%。当总量高于约30重量%时,这些化合物可能无法溶于油脂中。当总重低于约0.01重量%时,无法充分地显示本发明的效果。这些化合物,与噻唑啉二酮衍生物比如曲格列酮和匹格列酮相似,具有PPARγ配体活性因此可有效改善胰岛素耐受性并预防和/或改善与生活方式相关疾病比如构成代谢性综合症的内脏脂肪肥胖症、II型糖尿病、高脂血和高血压。
包含于本发明经加工的油脂组合物中的光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B有效抑制和/或改善由营养过剩比如摄入高脂/高糖食物引起的体重增加。
本发明所用的光甘草定、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B是归类于异黄烷的黄酮类化合物,是由下面通式(1)代表的化合物:
[式1]
其中,在光甘草定中,R1=H,R2=OH;在3′-羟基-4′-邻-甲基光甘草定中,R1=OH,R2=OCH3;在4′-邻-甲基光甘草定中,R1=H,R2=OCH3;以及在欧甘草素B中,R1和R2一起是-CH=CH-C(CH3)2-O-从而构成6-元环。
本发明所用的光甘草素是归类于异黄-3-烯(isoflav-3-ene)的黄酮类化合物,是由下面通式(2)代表的化合物:
[式2]
本发明所用的光甘草酚是归类于二氢黄酮的黄酮类化合物,是由下面通式(3)代表的化合物:
[式3]
光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B是特别包含于甘草中光果甘草中的成分,几乎不包含于其它种属中。但是,这些化合物可包含于光果甘草与其它种属的杂交物中。这些化合物可与其它黄酮类化合物成分相分离,通过HPLC分析使用反相柱比如ODS检测并定量。
上述化合物的脂肪酸酯也可用于本发明中。这些酯可由任意有机酸或无机酸形成。为了适应本发明的目的,可使用用于食物、饮料、药物或化妆品的适当的酸。优选地,可使用脂肪酸。脂肪酸可包括但不限于长链脂肪酸比如油酸、棕榈酸、硬脂酸、亚油酸或亚麻酸;以及短链或中链脂肪酸比如丁酸或乙酸。
本发明还可适当地使用上述化合物的盐。这些化合物的溶液可以与适用于食物、饮料、药物或化妆品的适当酸混合而形成,这些酸比如盐酸、硫酸、甲磺酸、富马酸、马来酸、琥珀酸、乙酸、安息香酸、草酸、柠檬酸、酒石酸、碳酸或磷酸。当该化合物具有酸性部分时,可使用可用于食物、饮料、药物或化妆品的适当的盐。该盐包括与碱金属盐形成的盐比如钠、钾盐;碱土金属盐比如钙或镁盐;以及合适的有机配位体比如季铵盐。
与糖部分通过一种或多种羟基结合的糖苷可合适地用于本发明中。糖部分可以是任意糖。糖部分可包括但不限于单糖、二糖、三糖、寡糖和多糖。
当该化合物具有至少一个不对称中心时,它可以存在对映体形式。当该化合物具有至少两个不对称中心时,它可以存在非对映体形式。这样的异构体和其任意比例的混合物均可包括在本发明的范围内。该化合物可以被任选取代。
在本发明中,并不特别限制制备光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的方法,这些化合物可通过光果甘草获得。当从甘草获得这些化合物时,并不特别限制其方法,这些化合物可包含于通过有机溶剂比如乙醇、乙酸乙酯和丙酮萃取而得的疏水性甘草萃取物中,并可使用该萃取物本身,但也可使用经柱处理、除臭处理、脱色处理等纯化疏水性萃取物而得的粗或纯产物。当然,本发明所用的化合物可以是来源于天然物质比如其它植物的化合物、化学合成的化合物或在培养细胞中生物合成的化合物。所用化合物可以是纯化的化合物,但也可使用经纯化仍为粗品形式的化合物,只要它们不含不适于饮食品、医药、非医药或化妆品等的杂质即可。
用于本发明的油脂是脂肪酸甘油酯包括中链脂肪酸甘油三酯,优选该脂肪酸甘油酯包含至少约50wt%的中链脂肪酸甘油三酯,更优选该脂肪酸甘油酯包含至少约70wt%的中链脂肪酸甘油三酯。该中链脂肪酸甘油三酯包含约C6至C12脂肪酸作为组分的脂肪酸,其中脂肪酸的组分比例没有具体的限制,但约C8至C10脂肪酸组分的比例优选至少约50wt%或更多,更优选至少约70wt%或更多。具体地,更优选中链脂肪酸甘油三酯在约20℃时比重约为0.94至0.96,在约20℃时粘度约为23至28cP。所用的中链脂肪酸甘油三酯可以来源于天然物质或通过酯交换制备。
用于本发明的油脂是包含偏甘油酯的脂肪酸甘油酯,优选包含至少约50wt%或更多偏甘油酯的脂肪酸甘油酯,更优选包含至少约70wt%或更多偏甘油酯的脂肪酸甘油酯。该偏甘油酯是甘油二酯(1,2-二酰甘油,1,3-二酰甘油)或甘油单酯(1-单酰基甘油,2-单酰基甘油),且可使用甘油二酯和/或甘油单酯,但从加工性能的观点来看,优选甘油二酯。所用的偏甘油酯可以来源于天然物质或通过酯交换制备。
作为用于该本发明的油脂,可以使用中链脂肪酸甘油三酯和偏甘油酯的混合物,或可以使用中链脂肪酸的偏甘油酯。
在本发明中,并不特别限制将光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B溶解在油脂中的方法,且可通过常规的搅拌或混合过程完成。当使用包含这些化合物的萃取物或这些化合物的粗精制品时,由于在其中包含这些化合物以外的杂质,因此当这些化合物通过搅拌或混合过程溶解于油脂中时,通过比如过滤或离心过程合意地除去不溶于油脂的杂质。当使用这些化合物的纯化制品时,可方便地获得溶液。当使用包含这些化合物的萃取物或这些化合物的粗精制品时,其溶解于有机溶剂比如乙醇中,然后将所得溶液与油脂混合,并蒸除有机溶剂。
通常,粉末态的光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B不稳定,即使将这些化合物溶解于有机溶剂比如乙醇中仍无法改善这些化合物的稳定性。但是,这些化合物的稳定性可通过将它们溶解于本发明所用的油脂中而改善。此外,这些化合物在水中微溶,所述化合物的吸收率可通过溶解于本发明所用的油脂中而改善。
本发明的组合物可以包含适用于食物、饮料、药物或化妆品的赋形剂。赋形剂可以是例如任何惰性的、适于口腔、肠内、透皮、皮下或肠胃外给药的有机或无机物。赋形剂可包括但不限于水、明胶、阿拉伯胶、乳糖、微晶纤维素、淀粉、淀粉乙醇酸钠、磷酸氢钾、硬脂酸镁、滑石粉以及胶体二氧化硅等。该组合物还可包含其它药理学试剂和常规添加剂比如稳定剂、润湿剂、乳化剂、调味剂以及缓冲剂等。
根据本发明用于预防和/或改善与生活方式相关疾病的经加工的油脂组合物和/或用于抑制和/或改善体重增加的经加工的油脂组合物,可用于饮食品比如保健食物,具有保健要求的食物(用于特定用途[FOSHU]和具有营养功能要求的食物),医药,非医药或化妆品等,对它们的形式没有特殊要求。例如,具有至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物的油脂可单独用于烹调、软胶囊和洗剂。此外,它们可与油部分自由地混合,并因此按照目的与其它油脂混合以调节它们的物理性能。在这种情况下,另一种油脂优选是食物或医药,它们的类型和用量取决于个别产品所需的物理性能或各种情况比如应用它们时的温度范围,其性质比如粘度和熔点可通过调节它们的类型和用量而得以控制。例如可以使用植物油比如玉米油、菜籽油、高芥酸菜籽油(high erucic rapeseed oil)、豆油、橄榄油、红花油、棉子油、向日葵油、米糠油、棕榈油和棕榈核油,动物油类比如鱼油、牛油、猪油、乳脂以及蛋黄油,或以上述油类作为起始物质通过分馏法、氢化或酯交换获得的油脂,或其混合油。
通过上述方法获得的经加工的油脂组合物可用作液体油脂比如色拉油和油炸油以及用作塑料油脂比如人造黄油和起酥油,并且可用于油包水型乳液和水包油型乳液。经加工的油脂组合物可通过喷雾干燥转化成粉剂从而用作粉状的油脂。用于由这些油脂作为初始物质生产的食物、饮料的经加工的油脂组合物包括各种类型的补充物,比如软胶囊、硬胶囊、片剂、咀嚼剂、条带和香料袋,糖果类比如口香糖、巧克力、硬糖、果冻、饼干和薄脆饼干,冷冻糖果比如冰淇淋和冰点心,饮料比如乳制饮料、软饮料、维生素饮料和美容饮料,面条比如切面(稠白面条)、中国面条、意大利面和冲泡式中国面条,清蒸鱼糊制备的产品比如鱼糕(清煮鱼香肠)、圆筒状鱼糕(管状的蒸烤鱼糊卷)和鱼肉山芋丸子(由底栖鱼制成的清淡、疏松的饼块),和调料比如调味品、蛋黄酱和酱汁,以及面包、火腿、汤、各种杀菌包装食品和各种冷冻食品,且该用于食物和饮料的经加工的油脂组合物还可以用于宠物食物和家畜饲料。
为营养富集目的,可在使用的同时加入各种的维生素比如维生素A、C、D和E,或在使用的同时加入调味剂比如各种的盐、香料、牛奶-相关物比如全脂奶粉、脱脂奶粉、发酵牛奶和乳脂。除了上述起始材料外,可使用用于常规水包油型乳状液和油包水乳状液的任何抗氧化剂和着色剂。
当经加工的油脂组合物用作软胶囊制剂时,每个胶囊所包含的至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物总量约为0.01至150mg,优选约0.1至150mg,更优选约1至50mg。取决于不同目的,可进一步加入各种维生素比如维生素A、C、D和E,制剂基质物质比如蜂蜡以及乳化剂。在这种情况下,乳化剂包括但是不局限于,脂肪酸甘油酯,脂肪酸糖酯,去水山梨糖醇脂肪酸酯,聚山梨酸酯和磷脂。在这些化合物之中,优选脂肪酸甘油酯,并且更优选聚甘油脂肪酸酯。聚甘油脂肪酸酯特别优选二甘油一油酸或聚甘油-缩合的蓖麻油酸酯。
包含于根据本发明用于预防和/或改善与生活方式相关疾病的经加工的油脂组合物、和/或用于抑制和/或改善体重增加的经加工的油脂组合物中的光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B,在经加工的油脂组合物的含量合意地为:允许所摄入的这些化合物的总量为每成年人每天约0.01至10mg/kg(体重),优选约0.1至1mg/kg,从而显示它们抑制和/或改善与生活方式相关疾病和/或抑制和/或改善体重增加的效果。
但是,虽然有效量可根据年龄、体重、健康情况、对象病情的严重程度、摄入的方式和时间、哺乳动物对象的排泄比例或组合物的合用而改变,但可以通过本领域技术人员已知的方法经实验或凭经验确定。本发明提供了用于预防和/或改善与生活方式相关疾病的方法,包括给予需要或不需要的哺乳动物对象本发明的组合物。可通过对象自身或保健人员对改善程度进行评价,可以主观的(例如意见)或客观的(例如可通过测试或诊法测量)。
实施例
在下文,本发明参考实施例进行详细描述,但本发明不局限于实施例。
实施例1
9.85kg收获于阿富汗的甘草(光果甘草)经乙醇萃取(于45℃在两小时内使用49.25L萃取两次),然后浓缩所得萃取液得到4.4L浓缩液。进一步浓缩3L浓缩液,然后施用活性炭处理并浓缩得到811.2g包含疏水性甘草萃取物的乙醇溶液。剩下的浓缩液(1.4L)用于比较实施例1中。
将上述乙醇溶液629.2g(包含125.8g疏水性甘草萃取物),与187.6g的Actar M-2(具有C8∶C10=99∶1的脂肪酸组成的中链脂肪酸甘油三酯[MCT],由Riken Vitamin制造)混合,然后在搅拌下将该混合物保持在80℃约1小时,减压浓缩除去乙醇。抽滤浓缩物以分离不溶物,过滤后,进一步向滤液中加入45.7g的MCT,得到297.0g的MCT溶液作为经加工的油脂组合物。
将所得的MCT溶液1g,溶于HPLC用甲醇中形成总体积为100ml的溶液。在下面条件下使用HPLC分析该溶液样品,结果每克MCT溶液中所包含的光甘草素、光甘草定、光甘草酚和4′-邻-甲基光甘草定的量分别为6.6mg、30.8mg、12.6mg和3.7mg(总量53.7mg;含量5.4重量%)。
HPLC分析条件
使用了分析柱J’sphere ODS-H80,4.6×250mm(YMC),柱温为40℃。作为流动相,使用20mM磷酸水溶液和乙腈,流速为1ml/min,梯度条件为乙腈在开始分析后20分钟内维持在35%,然后在20分钟至75分钟内线性升高至70%,在75分钟至80分钟内升高至80%。注射体积为20μl,检测波长为254nm。各化合物的保留时间为:光甘草素40.0分钟、光甘草定50.2分钟、光甘草酚58.3分钟、4′-邻-甲基光甘草定66.8分钟。
比较实施例1
将实施例1中所用的浓缩物蒸发至干并研磨得到疏水性甘草萃取物,然后将其100mg溶解于HPLC用甲醇中形成总体积为100ml的溶液。使用HPLC分析该溶液样品,结果每克疏水性甘草萃取物中所包含的光甘草素、光甘草定、光甘草酚和4′-邻-甲基光甘草定的量分别为16.5mg、90.4mg、34.1mg和9.3mg。
比较实施例2
将100mg实施例1中所用的乙醇溶液溶解于HPLC用甲醇中形成20ml的溶液。使用HPLC分析该溶液样品,结果每克乙醇溶液中所包含的光甘草素、光甘草定、光甘草酚和4′-邻-甲基光甘草定的量分别为3.4mg、18.7mg、7.1mg和1.9mg。
贮存稳定性测试
于80℃的加速试验中进行光甘草素、光甘草定、光甘草酚和4′-邻-甲基光甘草定在上述MCT溶液中的贮存稳定性试验。MCT溶液保存于80℃的水浴中,分别贮藏1、3和5小时后测定光甘草素、光甘草定、光甘草酚和4′-邻-甲基光甘草定的含量。贮存稳定性表示为贮藏后的含量与贮藏前含量的比例,假定贮藏前各化合物的含量为100%。
贮存稳定性试验的结果示于表1中。在该表中,化合物1表示光甘草素,化合物2表示光甘草定,化合物3表示光甘草酚,化合物4表示4′-邻-甲基光甘草定。
经类似方式完成比较实施例1中疏水性甘草萃取物的贮存稳定性试验。结果示于表2中。
经类似方式完成比较实施例2中乙醇溶液的贮存稳定性试验。结果示于表3中。
表1
MCT溶液 | 贮存稳定性 | |||
化合物1 | 化合物2 | 化合物3 | 化合物4 | |
开始时 | 100% | 100% | 100% | 100% |
1小时后 | 100% | 100% | 101% | 97% |
3小时后 | 99% | 101% | 103% | 103% |
5小时后 | 97% | 97% | 99% | 97% |
表2
疏水性甘草萃取物 | 贮存稳定性 | |||
化合物1 | 化合物2 | 化合物3 | 化合物4 | |
开始时 | 100% | 100% | 100% | 100% |
1小时后 | 91% | 91% | 97% | 92% |
3小时后 | 88% | 88% | 101% | 98% |
5小时后 | 85% | 86% | 103% | 99% |
表3
乙醇溶液 | 贮存稳定性 | |||
化合物1 | 化合物2 | 化合物3 | 化合物4 | |
开始时 | 100% | 100% | 100% | 100% |
1小时后 | 94% | 96% | 95% | 89% |
3小时后 | 93% | 94% | 95% | 93% |
5小时后 | 91% | 93% | 95% | 90% |
化合物1至4在MCT溶液中稳定,然而在疏水性甘草萃取物和乙醇溶液中,尤其是化合物1和2不稳定,且随着贮藏时间的推移而含量减少。
根据这些结果,揭示了化合物1和2在疏水性甘草萃取物和乙醇溶液中不稳定,而化合物1至4在MCT溶液中稳定。该测试是80℃的加速试验,由此揭示了它们在大约室温的条件下可稳定存在几天至几个月。
实施例2
从包含51.9g疏水性甘草萃取物和468.2g MCT的103.7g乙醇溶液中,经与实施例1相同的方法获得497.4g的MCT溶液。该MCT溶液经HPLC分析,结果每克MCT溶液中所包含的光甘草素、光甘草定、光甘草酚和4′-邻-甲基光甘草定的量分别为1.2mg、12.3mg、1.9mg和0.9mg(总量16.3mg;含量1.6重量%)。
实施例3
对于减少内脏脂肪的作用和抑制体重增加的作用
允许C57BL/6J小鼠(雌性,8周龄)不限量地接受高脂/高糖饮食8周以引起饮食-诱发的肥胖症。所用的高脂/高糖饮食是半固体纯化饲料,包含25wt%酪蛋白、14.869wt%玉米淀粉、20wt%蔗糖、2wt%豆油、14wt%猪油、14wt%牛脂、5wt%纤维素粉、3.5wt%AIN-93矿物混合物、1wt%AIN-93维生素混合物、0.25wt%重酒石酸胆碱、0.006wt%叔丁基对苯二酚和0.375wt%L-胱氨酸(Oriental Yeast Co.,Ltd.)。
此后,将小鼠分为4组(组A、B、C和D,分别含有10只小鼠),不限量向各组给予粉状高脂/高糖饮食8周,其中所述粉状高脂/高糖食物中已加入如表4所示的实施例2中的MCT溶液和MCT。如同MCT一样,使用Actar M-2(Riken Vitamin)。
给予样品后,在乙醚麻醉下打开各小鼠腹腔,通过腹部大动脉血液采血并处死小鼠后,移除肠系膜脂肪、肾周脂肪和子宫周脂肪然后称重。肠系膜脂肪、肾周脂肪和子宫周脂肪的总重被认为是腹内脂肪重量。各组重量的变化和所测量的脂肪重量的变化示于表5中。
各组摄取饲料量没有可识别的差异,但组B至D与组A相比可看出对体重增加的明显抑制作用。比较组B至D与组A还可看出肠系膜脂肪、肾周脂肪、子宫周脂肪和腹内脂肪的显著减少。也就是说,向已由高脂/高糖引起饮食-诱发肥胖症的小鼠提供其中加入了至少1%实施例2中的MCT溶液的食物时,其显示了对增加体重具有显著的抑制作用并且对腹内脂肪的累积具有显著的抑制作用。
由此,包含光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的MCT溶液,显示了对体重增加有效的抑制作用,并且在摄取高脂/高糖食物等过量营养的情况下减少内脏脂肪。
表4
组 | 含量 | |
MCT溶液 | MCT | |
组A | - | 3wt% |
组B | 1wt% | 2wt% |
组C | 2wt% | 1wt% |
组D | 3wt% | - |
表5
组A | 组B | 组C | 组D | |
体重(g)起始时8周后 | 27.8±3.231.7±4.1 | 27.6±2.927.2±3.7* | 27.7±2.925.8±2.3** | 27.5±2.824.6±1.2** |
摄取饲料的平均量(g/天/小鼠) | 2.15 | 2.21 | 2.08 | 1.95 |
脂肪量(g)-肠系脂肪-肾周脂肪-子宫周脂肪-腹内脂肪 | 0.615±0.1840.912±0.4331.279±0.4372.806±1.042 | 0.306±0.109*0.446±0.2070.670±0.3531.421±0.647 | 0.238±0.093**0.305±0.181**0.457±0.205**1.000±0.461** | 0.184±0.049**0.186±0.076**0.307±0.131**0.667±0.238** |
均值±SE(n=10),*(P<0.05)**(p<0.01)
实施例4
软胶囊剂的制备(1)
通过旋转式软胶囊制造装置将实施例1中的MCT溶液注射入明胶膜中得到含量为350mg的软胶囊。每一软胶囊中所包含的光甘草素、光甘草定、光甘草酚和4′-邻-甲基光甘草定的量分别为2.3mg、10.8mg、4.4mg和1.3mg(总量18.8mg;含量5.4重量%)。
软胶囊剂的制备(2)
在57重量份的MCT(Actar M-2,Riken Vitamin Co.Ltd.)中,将3重量份的一缩二甘油单油酸酯(diglycerin monooleate)(DO-100V,Riken Vitamin)溶解,并在搅拌下向其中加入40重量份实施例1中的MCT溶液以制备均匀溶液。
通过旋转式软胶囊制造装置将该溶液注射入明胶膜中得到含量为350mg的软胶囊剂。每一软胶囊中所包含的光甘草素、光甘草定、光甘草酚和4′-邻-甲基光甘草定的量分别为0.9mg、4.3mg、1.8mg和0.5mg(总量7.5mg;含量2.1重量%)。
实施例5
粉末油脂的制备
在400重量份的水中,溶解70重量份的糊精和20重量份的酪蛋白钠制得水相。
向制备的水相中,搅拌下加入10重量份实施例1中的MCT然后经匀化器乳化,所得乳剂经喷雾干燥得粉末油脂。
实施例6
人造黄油的制备
向80重量份的硬棉花籽油(商标名:Snow Light,Kanegafuchi ChemicalIndustry Co.,Ltd.)中加入20重量份的实施例1中的MCT溶液和10重量份的无盐黄油(Yotsuba Nyugyo Co.,Ltd.)、0.2重量份的甘油单脂肪酸酯(商标名:Emulgy MS,Riken Vitamin)和0.2重量份的卵磷脂,然后于60℃加热溶解制备油相。
向84.9重量份已制备的油相中,搅拌下加入15.1重量份水,然后乳化20分钟,此后冷却并经配合器揉捏制备人造黄油。
实施例7
浓乳(conc.milk)的制备
将10重量份实施例1中的MCT溶液加热至70℃以后,依次在其中溶解0.1重量份的卵磷脂和0.1重量份的聚甘油脂肪酸酯以制备油相。
单独地,于60℃将25重量份的粉状脱脂奶、0.1重量份的脂肪酸甘油酯和0.1重量份的脂肪酸糖酯溶于64.6重量份的水中制备水相。
预先乳化所制备的水相和油,相然后在145℃使用UHT消毒器灭菌4秒钟。然后,真空冷却该乳剂并在10MPa压力下使用均质器搅匀然后用平板冷却至10℃得到加工的浓乳。
实施例8
蛋黄酱的制备
向混合器中加入10重量份的醋、1重量份的食盐、0.6重量份的糖、0.2重量份的芥末粉和0.2重量份的谷氨酸钠,然后在15至20℃搅拌并混合以制备水相。然后,将10重量份的蛋黄加入至68重量份的米白色压榨油和10重量份实施例1MCT溶液中,然后在搅拌下乳化该混合物制备乳剂(10至15℃),在15至20℃搅拌下将该乳剂逐渐加入上述水相得到预乳化混合物。然后,使用胶体磨乳化该混合物得到蛋黄酱。
工业实用性
根据本发明,可提供用于预防和/或改善与生活方式相关疾病的经加工的油脂组合物(加工的油脂组合物或加工的包含油类和脂类的组合物),和/或用于抑制和/改善体重增加的经加工的油脂组合物,其可用于食物和饮料比如保健食品、具有保健要求的食物(用于特定用途[FOSHU]的使用和具有营养功能要求的食物)、医药、非医药、化妆品等。该经加工的油脂可有效改善胰岛素耐受性,预防和/或改善与生活方式相关疾病比如内脏脂肪肥胖症、II型糖尿病、高脂血症和高血压,和/或抑制和/或改善肥胖症即体重增加。
Claims (17)
1.一种用于预防和/或改善与生活方式相关疾病的经加工的油脂组合物,其中在油脂中溶解有至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物或其盐、酯或糖苷,其中这些化合物的总量为基于该组合物重量的约0.01至30重量%。
2.一种用于抑制和/或改善体重增加的经加工的油脂组合物,其中在油脂中溶解有至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物或其盐、酯或糖苷,其中这些化合物的总量为基于该组合物重量的约0.01至30重量%。
3.一种用于改善胰岛素耐受性的经加工的油脂组合物,其中在油脂中溶解有至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物或其盐、酯或糖苷,其中这些化合物的总量为基于该组合物重量的约0.01至30重量%。
4.根据权利要求1至3任一项的经加工的油脂组合物,其中所包含的选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B中至少一种的化合物或其盐、酯或糖苷的量,应使得每成年人每天对这些化合物总量的摄取量约为0.01至10mg/kg体重。
5.根据权利要求1至4任一项的经加工的油脂组合物,其中油脂包含脂肪酸甘油酯,该脂肪酸甘油酯包含中链脂肪酸甘油三酯和/或偏甘油酯。
6.根据权利要求1至5任一项的经加工的油脂组合物,其中油脂包含脂肪酸甘油酯,该脂肪酸甘油酯包含约50重量%或更多的中链脂肪酸甘油三酯。
7.根据权利要求1至5任一项的经加工的油脂组合物,其中油脂包含脂肪酸甘油酯,该脂肪酸甘油酯包含约50重量%或更多的偏甘油酯。
8.根据权利要求1的经加工的油脂组合物,其中与生活方式相关疾病包括选自内脏脂肪肥胖症、II型糖尿病、高脂血症和高血压中的至少一种疾病。
9.根据权利要求1的经加工的油脂组合物,其中与生活方式相关疾病是内脏脂肪肥胖症和/或II型糖尿病。
10.根据权利要求1至9任一项的经加工的油脂组合物,其为饮食用。
11.根据权利要求1至9任一项的经加工的油脂组合物,其为医药用。
12.根据权利要求1至9任一项的经加工的油脂组合物,其用于美容。
13.一种软胶囊制剂,其包含被包封于其中的根据权利要求1至12的经加工的油脂组合物。
14.根据权利要求13的软胶囊制剂,其包含至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物或其盐、酯或糖苷,每一胶囊中这些化合物的总量为约0.01至150mg。
15.根据权利要求1至14任一项的经加工的油脂组合物,其中至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物或其盐、酯或糖苷是从光果甘草中获得的。
16.用于制备根据权利要求1至15任一项的组合物的方法,其包括将至少一种选自光甘草素、光甘草定、光甘草酚、3′-羟基-4′-邻-甲基光甘草定、4′-邻-甲基光甘草定和欧甘草素B的化合物或其盐、酯或糖苷溶解于油脂中。
17.一种用于预防和/或改善哺乳动物与生活方式相关疾病的方法,其包括向需要其的哺乳动物对象给予有效量的根据权利要求1至15任一项的组合物。
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CN (1) | CN1777420A (zh) |
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Cited By (3)
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WO2011095095A1 (zh) * | 2010-02-06 | 2011-08-11 | 桂林商源植物制品有限公司 | 一种含有醇溶性且非水溶性甘草提取物的药物组合物,及其药物制剂、制药用途、治疗方法和制备方法 |
CN102771673A (zh) * | 2012-08-14 | 2012-11-14 | 江苏美迪森生物医药有限公司 | 一种构建代谢综合症动物模型的高脂纯化饲料及加工工艺 |
CN111713503A (zh) * | 2020-07-16 | 2020-09-29 | 江苏省中国科学院植物研究所 | 两种异黄酮类化合物在防治植物病害中的用途 |
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EP1864643A4 (en) * | 2005-03-30 | 2011-08-17 | Kaneka Corp | PREPARATION CONTAINING OIL / FATS FOR INHIBITING THE DEVELOPMENT OF CANCER |
KR20070052211A (ko) * | 2005-11-16 | 2007-05-21 | 주식회사 엠디바이오알파 | 글라브리딘을 유효성분으로 함유하는 질환 증후군 예방 및치료용 조성물 |
WO2007060992A1 (ja) * | 2005-11-25 | 2007-05-31 | Kaneka Corporation | メタボリックシンドロームもしくはインスリン抵抗性症候群の予防または改善剤 |
TW200806306A (en) * | 2006-02-24 | 2008-02-01 | Kaneka Corp | Oil-in-water emulsion composition containing licorice-derived polyphenol |
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EP2163252A4 (en) * | 2007-05-17 | 2012-01-11 | Kaneka Corp | COMPOSITION CONTAINING A POLYPHENOL DERIVED FROM THE LICENSE |
US20090042813A1 (en) * | 2007-08-10 | 2009-02-12 | Sergey Michailovich Melnikov | Hoodia extract oil compositions comprising medium chain triglycerides |
WO2009025277A1 (ja) * | 2007-08-22 | 2009-02-26 | Kaneka Corporation | 還元型補酵素q10の製造方法、ならびに、その安定化方法 |
JP2011231057A (ja) * | 2010-04-28 | 2011-11-17 | Kao Corp | セラミド産生促進剤 |
ES2964146T3 (es) * | 2016-06-29 | 2024-04-04 | Glaceum Inc | Derivado de piranocromenilfenol ópticamente activo y composición farmacéutica que lo comprende |
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JP2794433B2 (ja) * | 1989-02-02 | 1998-09-03 | 丸善製薬株式会社 | 甘草疎水性フラボノイド製剤 |
JP4418550B2 (ja) * | 1999-02-17 | 2010-02-17 | 丸善製薬株式会社 | 疎水性甘草エキス含有組成物 |
TWI329516B (en) * | 2000-12-12 | 2010-09-01 | Kaneka Corp | Composition for preventing or ameliorating multiple risk factor syndromes and visceral fat-type obesity |
CN1599602A (zh) * | 2001-10-11 | 2005-03-23 | 钟渊化学工业株式会社 | 过氧化物酶体增殖剂应答性受体配体剂及其制备方法 |
WO2003074043A1 (fr) * | 2002-03-04 | 2003-09-12 | The Nisshin Oillio Group Ltd. | Agents destines a elever la temperature corporelle |
JP4191420B2 (ja) * | 2002-03-26 | 2008-12-03 | 株式会社カネカ | 甘草疎水性抽出物を含有してなる食用油脂組成物 |
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- 2004-07-14 WO PCT/JP2004/010381 patent/WO2005011672A1/ja not_active Application Discontinuation
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WO2011095095A1 (zh) * | 2010-02-06 | 2011-08-11 | 桂林商源植物制品有限公司 | 一种含有醇溶性且非水溶性甘草提取物的药物组合物,及其药物制剂、制药用途、治疗方法和制备方法 |
CN102771673A (zh) * | 2012-08-14 | 2012-11-14 | 江苏美迪森生物医药有限公司 | 一种构建代谢综合症动物模型的高脂纯化饲料及加工工艺 |
CN111713503A (zh) * | 2020-07-16 | 2020-09-29 | 江苏省中国科学院植物研究所 | 两种异黄酮类化合物在防治植物病害中的用途 |
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US20070098761A1 (en) | 2007-05-03 |
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