CN100334973C - 控制体重的组合物和方法 - Google Patents
控制体重的组合物和方法 Download PDFInfo
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- CN100334973C CN100334973C CNB018117139A CN01811713A CN100334973C CN 100334973 C CN100334973 C CN 100334973C CN B018117139 A CNB018117139 A CN B018117139A CN 01811713 A CN01811713 A CN 01811713A CN 100334973 C CN100334973 C CN 100334973C
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Abstract
本发明涉及控制个体体重的组合物以及用所述组合物控制体重的方法。控制体重,尤其是体重增加或减少,是通过在所述个体中产生饱腹感而完成的。这种控制体重的方法包括在进食之前施用这种组合物,在进食时施用这种组合物,作为食物的代替物食用,以及结合使用这些方法。
Description
发明背景
美国普通人群中肥胖症的发病率在过去的十年中有惊人的增长,有超过50%的人口超重或肥胖。在其它采用西式饮食的国家也有类似的趋势。由于肥胖与许多并发症有关,如糖尿病、高血压、动脉粥样硬化等,这些增长对健康有很大影响。
已经提出或使用了很多方法以帮助个体减少食物摄取(或称为能量摄取)并由此控制他们的体重。这些方法包括使用作用于中枢神经系统以增加血清素水平的药物,以及作用于肠胃道以降低消化和/或营养吸收的药物。这些方法有潜在的副作用,这就使其不能长期使用以控制体重。
不同的方法包括采用营养物质直接进入小肠末梢以减少相伴食物的摄取。这种方法使用了天然物质,并被认为是经营养物质与假想的遍布于小肠,尤其是小肠末梢(空肠、回肠)的受体相互作用而发挥作用,小肠末梢被认为参与了诱导进食终止的天然机制。这就提供了潜在的优点,即由于使用了天然物质和机制而减小了副作用。
在动物和人类中报道的数据分别使用了导管和鼻饲管以将营养物质直接引入它们的小肠中。报道的研究大多使用了脂质体。例如,在进食的同时将玉米油乳剂灌注入小肠(空肠或回肠)以降低饮食中食物的摄取,这样所摄取的总卡路里(饮食和灌注物)就会明显或直接降低;参见I.Welch,K.Saunders和N.W.Read,
Effect of Ileal and Intravenous Infusions of Fat Emulsions on Feeding and Satiety in Human Volunteers,Gastroenterology 89:1293-1297,1985;I.Welch,C.P.Sepple和N.W.Read,
Comparisons of the Effects on Satiety and Eating Behavior of Infusion of Lipid into the Different Regions of the Small Intestine,Gut29:306-311,1988;在此全文并入以供参考。个别实验中,静脉施用三酰基甘油乳剂(Intralipid)不能降低总卡路里;参见I.Welch,K.Saunders和N.W.Read,同上;E.K.Walls和H.S.Koopmans,
Effect of Intravenous Nutrient Infusions on Food Intake in Rats,Physiiology & Behavior 45:1223-1226,1989;在此全文并入以供参考。预先食用酸奶中的三酰基甘油不能减少随后正餐中总卡路里的摄取(正餐和预餐);参见B.J.Rolls,S.Kim,A.L.McNeils,M.W.Fischman,R.W.Foltin和T.H.Moran,
Time Course of Effects of Preloads High in Fat or Carbohydrate on Food Intake and Hunger Ratings in Humans,Am.Journl.Physiology,260:R756-R763,1991;J.H.Meyer,M.Hlinka,A.Khatibi和H.E.Raybould,
Role of Small Intestine in Caloric Compensations to Oil Premeals in Rats,Am.Journl.Physiology,275:R1320-R1333,1998;在此全文并入以供参考。
在许多动物研究中,营养物质被灌输进小肠以减少食物摄取。例如,Woltman等披露到,被灌输进十二指肠的油酸胶束溶液在大鼠中将4小时食物摄取减少的程度大于三油酸甘油酯溶液,且十二指肠灌输较之回肠灌输能更有效的减少食物摄取;参见T.Woltman和R.Reideberger,
Effect of Duodenal and Distal Ileal infusions of Glucose and Oleic Acid on Meal Patterns in Rats,Am.Journl.Physiology,269:R7-R14,1995;T.Woltman,D.Castellanos和R.Reidelberge,
Role of Cholecystokinin in the Anorexia Produced by Duodenal Delivery of Oleic Acid in Rats,Am.Journl.Physiology,269:R1420-R1433,1995;在此全文并入以供参考。Greenberg等披露到,在假饲大鼠模型中,十二指肠灌输的三酰基甘油乳剂和亚油酸乳剂减少了总卡路里的摄取,而回肠灌输却不能;参见D.Greenberg,G.P.Smith和J.Gibbs,
Intraduodenal Infusions of Fats Elicit Satiety in Sham Feeding Rats,Am.Journl.Physiology,259:R110-R118,1990;D.Greenberg,G.P.Smith和J.Gibbs,
Intravenous Triglycerdies Fail to Elicit Satiety in Sham-Feeding Rats,Am.Journl.Physiology,264:R409-R413,1993;D.Greenberg,
Fats and Satiety:the Role of the Small Intestine,Appetite 31:229,1998;D.Greenberg,
Intestinal Satiety,in Satiation from Gut to Brain,G.P.Smith(编),第40-70页,牛津大学出版社,纽约,NY,1998;在此全文并入以供参考。对其它长链脂肪酸(油酸、亚油酸)不是很有效。
Meyer等进行了一系列研究,在强制饲养3小时的大鼠中调查了灌输的营养物质对总卡路里摄取。他们发现,当灌输进十二指肠或中肠(空肠)或结肠时,超过10个碳长度的脂肪酸的乳剂、仅仅对葡萄糖转运蛋白有亲和性的碳水化合物单体的溶液、以及色氨酸和苯丙氨酸的氨基酸溶液抑制了总卡路里的摄取。这些研究者还证明,在强制饲养7小时的大鼠中,三酰基甘油的预餐不能抑制总卡路里的摄取;参见J.H.Meyer,M.Hlinka,Y.Tabrizi,N.DiMaso和H.E.Raybould,
Chemical Specificities and Intestinal Distributions of Nutrient-Driven Satiety,Am.Journl.Physiology,275:R1293-R1307,1998;J.H.Meyer,Y.Tabrizi,N.DiMaso,M.Hlinka和H.E.Raybould,
Length of Intestinal Contact on Nutrient-Driven Satiety,Journl.Physiology,275:R1308-R1319,1998;在此全文并入以供参考。
最近,Cox等披露,空肠灌输的纯净的亚油酸或油酸(0.2mL/小时,进行7小时)会明显减少大鼠中每日总卡路里的摄取,而长链三酰基甘油(玉米油)则不能。这些人还证明,将这种减少作用持续给药20天会使接受治疗的动物与对照动物的体重明显不同;参见J.E.Cox,W.J.Tyler,A.Randich,G.R.Kelm,S.S.Bharaj,R.J.Jandacek和S.T.Meller,
Suppresion of Food Intake,Body Weight,and Body Fat by jejunal Fatty Acid Infusions,Am.Journl.Physiology,RegulatoryIntegrative Comparative Physiology,278:R604-R610,2000;在此全文并入以供参考。
据发明者所指,还没有这种研究,其中,含在药物剂型中的摄取或经胃给药的营养物质被设计成在小肠中释放营养物质用以减少食物的摄取。PCT申请WO87/03198号,美国专利第5,322,697号和5,753,253号揭示了采用这种药物制剂以减少食物摄取;在此全文并入以供参考。提供了灌输数据以支持这些发现。然而,没有提供关于使用设在小肠中释放营养物质以减少食物消耗和总卡路里摄取的肠营养物质剂型的数据。
此后,人们努力寻找采用天然营养物质以通过天然机制减少食物摄取的控制体重的方法。还需要一种含有可被人或动物摄取以减少食物的消耗并降低每日总卡路里摄取的营养物质的制品。
发明概述
本发明是关于组合物,以及用所述组合物控制人和动物个体体重的方法。本发明的组合物含有选自胃-肠酶类存在时能水解的长链脂肪酸、它们的非甘油酯、及其混合物的饱腹剂,其中所述的饱腹剂在胃中释放。组合物在进食之前施用,在进食时施用,作为食物的代替物食用,以及结合使用这些方法。食用本发明的组合物可在个体中产生足够时间的饱腹感,其中随后摄取食物的量有个体的食欲来控制。
本发明的一个目的是提供一种安全有效的组合物,食用本发明的这种组合物后能促进个体的体重控制。所述体重控制可与目前所用的进食法结合,并可对人和动物采用。另一个目的是提供一种控制食欲的方法,包括施用含有饱腹剂的组合物。
发明详述
本发明的基本原理是认识到,摄取含有长链未酯化的脂肪酸或是其非甘油酯有提高肝线粒体氧化作用的潜能,这是由于吸收了这种长链未酯化的脂肪酸。这样可能降低来自于三酰基甘油腔内水解产生的2-单酰基甘油的腔内水平。不局限于任何理论,发明者认为,当由本发明的组合物造成的肝线粒体对长链未酯化脂肪酸的氧化作用的迅速启动和速度增加与来自于三酰基甘油(这是饮食中脂肪酸的主要来源)的长链未酰化脂肪酸的氧化有关时,就可实现对食欲的控制。食欲控制是控制个体体重的主要因素。
因此,肝线粒体的长链未酯化脂肪酸的氧化速率被认为是控制食物摄取的重要因素。例如,向大鼠和人施用长链未酯化脂肪酸氧化抑制剂会增加食物的摄取。通过肝迷走神经切断术会增强这种效应,这说明肝脏在此类控制中是重要的组成元件;参见W.Langhans和E.Scharrer,
Role of Fatty Acid Oxidation in Control of Meal Pattern,Behavioral and Neural Biology 47:7-16,1987;M.I.Friedman,R.B.Harris,H.Ji,I Ramierez和M.G.Tordorr,
Fatty Acid Oxidation Affects Food Intake by Altering Hepatic Energy Status,Am.Journl.Physiology,276:R1046-R1053,1999;A.Kahler,M.Zimmermann和W.Langhans,
Suppression of Hepatic Fatty Acid Oxidation and Food Intake in Men,Nutrition 15:819-828,1999;W.Langhans和E.Scharrer,
Evidence for a Vagally Mediated Satiety Signal Derived from Hepatic Fatty Acid Oxidation,J.Autonomic Nervous System 18:13-18,1987;在此全文并入以供参考。因此,很显然,身体试图保持血液中长链未酯化脂肪酸的水平相对恒定,且这些水平是由肝线粒体对长链未酯化脂肪酸氧化作用的速率控制的(由传入迷走神经传递给大脑)。肝线粒体对长链未酯化脂肪酸氧化作用的降低会导致食物摄取的增加,而升高会导致食物摄取的减少。因此,提高肝线粒体对长链未酯化脂肪酸氧化作用的速率和程度的组合物将减少食物的摄取,并且便于对个体体重进行控制。
实际上,饮食中所有的长链脂肪酸都以三酰基甘油的形式摄入。三酰基甘油在小肠腔中被水解成长链的未酯化脂肪酸和2-单酰基甘油。然而,所得长链未酯化脂肪酸和2-单酰基甘油在肠细胞中被再酯化成三酰基甘油并变成由脂蛋白稳定的小的乳滴,这被称为乳糜微粒。在肠细胞的胞吐作用下,一部分乳糜微粒进入淋巴管而不是门静脉。大部分其它的营养和异生素被吸收进门静脉并在分配到身体其它部分之前定量的通过肝脏。然而,因为淋巴管流入血液循环随后再进入肝脏,所以来自三酰基甘油的摄取的脂肪酸首先以三酰基甘油的形式被分配到全身。在进食过程中,这些物质几乎没有以长链未酯化脂肪酸的形式到达肝脏从而影响食物的摄取。
据信,由于小肠腔中2-单酰基甘油减少,由本发明的组合物提供的一部分长链未酯化脂肪酸以长链未酯化脂肪酸通过门静脉被吸收。2-单酰基甘油水平的减少被认为减少了长链未酯化脂肪酸在肠细胞中的再酯化,并使一些被吸收的长链未酯化脂肪酸在被再酯化成三酰基甘油之前离开肠细胞的基底外侧并形成乳糜微粒。像这些离开肠细胞基底外侧的长链未酯化脂肪酸能进入门静脉并以可氧化的状态定量到达肝脏。相对于类似量的以三酰基甘油形式摄取的脂肪酸,它们具有大大提高肝线粒体氧化长链未酯化脂肪酸的速率的潜能。
由于本发明中不需要长链未酯化脂肪酸的末梢释放,因此不需要精心准备肠剂型以在小肠末梢释放长链未酯化脂肪酸。因此,本发明与已有技术有明显的改进,已有技术中实际上不含证明食物摄取减少是来自于这种假肠剂型的数据。
因此,本发明是关于组合物,使用所述组合物的方法以及用所述组合物控制体重的方法。体重的控制,尤其是体重增加或减少是通过在所述摄取本发明组合物的个体中产生饱腹感而完成的。
本发明的口服组合物含有选自胃-肠酶类存在时能水解的长链脂肪酸、它们的非甘油酯、及其混合物的饱腹剂,其中所述的饱腹剂在胃中释放。食用本发明的组合物可在个体中产生足够时间的饱腹感,其中随后摄取食物的量有个体的食欲来控制。
饱腹剂
奇怪的是,人们发现施用含有选自胃-肠酶类存在时能水解的长链(大于10个碳)未酯化的脂肪酸、它们的非甘油酯、及其混合物的饱腹剂的组合物后,在胃中释放的所述饱腹剂会减少总卡路里的摄取。这种饱腹剂可以各种形式施用,包括非肠道的药物剂型(如压缩片剂和模制片)、硬明胶胶囊、软的弹性明胶胶囊、以及在胃中溶解的微胶囊、乳剂和悬浮剂,或是饮料或固体食物制品的一部分。后者可作为正餐的补充或替代品。组合物应在进食之前一段时间施用以在个体中产生足够时间的饱腹感,其中随后摄取食物的量减少了,因此通过控制个体的食欲可减少总卡路里的摄取。这被认为是有效的控制体重的方法。
本发明的组合物含有选自胃-肠酶类存在时能水解的长链脂肪酸、它们的非甘油酯、及其混合物的饱腹剂,其中所述的饱腹剂在胃中释放。长链脂肪酸及其非甘油酯含有约12-24个碳,较好的是有16-18个碳原子。碳链中约有0-6个碳碳双键,较好的是约有0-3个。脂肪酸选自月桂酸、月桂烯酸、肉豆蔻酸、肉豆蔻烯酸、十五烷酸、棕榈酸、棕榈油酸、十七烷酸、硬脂酸、二羟硬脂酸、油酸、蓖麻油酸、反油酸、亚油酸、α-亚麻酸、二高γ-亚麻酸、桐酸、里卡利酸、花生四稀酸、花生酸、二十烯酸、二十碳五烯酸、山俞酸、芥子酸、二十二碳六烯酸、二十四酸以及它们的混合物。优选的脂肪酸选自油酸、亚油酸和它们的混合物。
非甘油脂肪酸酯包括(但不限于)醇酯,其中所述的这种酯的醇部分选自甲醇、乙醇、正丙醇、异丙醇、正丁醇、异丁醇以及它们的混合物,较好的是乙醇。优选的非甘油脂肪酸酯选自油酸乙酯、亚油酸乙酯及其混合物。
控制体重的方法
如本发明所述的组合物被用于动物或人,用药量为每千克体重施用约0.01克-10.0克所述饱腹剂,较好的是,用于所述个体的每份所述组合物的量为每千克体重约0.04克-1.0克饱腹剂。动物个体包括(但不限于)狗类、猫类、马类或其它类似的动物。“份”是指通常在指定时间摄取的组合物的量,其中的组合物可放在任何食物类型中,包括液体饮料(如奶昔、果汁等)和固体食物制品(如棒状物),或是放在药物剂型中,包括压缩片剂或模制片、软的和硬的明胶胶囊、微胶囊、乳剂和悬浮剂。较好的是,在设计或计划的控制体重方案的全过程中以日常途径采用所述的方法。
用本发明的组合物控制人和其它动物体重的方法包括以下步骤:在进食之前施用这种组合物,在进食时施用这种组合物,作为食物的代替物食用,以及结合使用这些方法。当在进食时服用时,本发明的组合物可与食物分别食用或制成含有所述组合物的食品。任何与所述发明一起食用的食物其三酰基甘油水平的最大值最好约为5克。当在进食前服用时,提前的时间应足够多,以防止其与摄入食物中的任何三酰基甘油成分发生实质性的相互反应,同时在所述进食其间增加肝的脂肪酸β-氧化作用和腹迷走神经的活性,从而尽早产生饱腹感并减少进食中能量的摄取。据信,在控制个体食欲的方法中所述组合物是有效的。
通常,可在进食前约30分钟至6小时时施用本发明的组合物。较好的是在个体每天的主餐之前(通常是早餐、午餐和晚餐)服用这种组合物。
也可用本发明的组合物替代所述个体一顿或多顿正餐。
添加成分
如上所述,此组合物可制成多种现有制品的形式。在这点上,在产品配方中可以使用许多添加成分以开发如此前所提到的商业上可接受的产品。一种广受欢迎的可被人食用的形式是有奶昔那样的稠度的稠的起泡饮料。用来制造这种产品的各种任选的成分包括悬浮剂、调味剂和粘度调节剂。其它特定的产品形式包括像片剂之类的药物剂型。用于片剂的任选成分包括(但不限于)稀释剂,如微晶纤维素;吸收剂,如胶体二氧化硅;崩解剂,如交联的羟甲基纤维素钠和交联的聚乙烯聚吡咯烷酮;粘合剂,如聚吡咯烷酮;表面活性剂,如聚氧乙烯烷基醚、聚氧乙烯蓖麻油衍生物、聚氧乙烯失水山梨糖醇脂肪酸酯以及甘油和多甘油脂肪酸的酯(不形成2-单酰基甘油);以及调味剂和甜味剂,根据所选试剂或各种饱腹剂的物理/化学性质,这些添加剂都为适当的量以便制成可用工业机器压制或模压的合适的片剂。硬明胶胶囊可含有任何所列出的用于片剂的任选成分,这可能需要合适的量以用工业机器制成硬的明胶。软的弹性明胶胶囊所含的任选成分通常包括表面活性剂,如聚氧乙烯烷基醚、聚氧乙烯蓖麻油衍生物、聚氧乙烯失水山梨糖醇脂肪酸酯以及甘油和多甘油脂肪酸的酯(不形成2-单酰基甘油)。除了表面活性剂,乳剂和悬浮剂中的任选成分还可以包括水胶体,如甲基纤维素、羟丙基甲基纤维素、黄原胶、瓜尔胶,以及调味剂和甜味剂。
实施例
以下是用常规方法制造的此组合物的非限制性的实施例。这种产品的这些实例通常以一份或一次剂量服用或输递,较好的是在进食前、进食时或代替食物一次食用。以下实施例只是为了阐述而不是以任何方式限制其范围。
现成的饮料
实施例I | 实施例II | 实施例III | |
成分 | (%w/v) | (%w/v) | (%w/v) |
天然盐氢氧化钠*Carageenan1纤维素胶2低粘度阿拉伯胶维生素/矿物质混合物3卵磷脂4甘油一酯和甘油二酯5油酸乙酯6可可粉7AF防沫乳剂*酪蛋白酸钠8高温脱脂乳粉麦芽糊精9砂糖Sucralose Liquid香草调味剂10奶油调味剂11香草调味剂12QS水总计 | 0.00620.01750.03500.52000.41000.43400.02610.04001.08111.20000.00200.29906.80002.43203.95000.05390.00150.00150.1000100.00 | 0.00620.01750.03500.52000.41000.43400.02610.04002.15051.20000.00200.29906.8000------3.95000.05870.00150.00150.1000100.00 | 0.00620.01750.03500.52000.41000.43400.02610.04003.24321.2000.00200.29906.8000------3.95000.05870.00150.00150.1000100.00 |
*操作助剂。需要时使用,指出了最大用量
1 SeaKem CM611和Viscarin SD389,皆来自于FMC
2 Avicel CL-611,来自FMC
3 FT-001106,来自于Fortitech
4 Centrolex-F,来自Central Soya股份有限公司
5 Myvatex 8-06,来自于Quest International USA,Inc.
6 05--58405,来自于Penta Manufacturing Co.,或Crodamol EO,来自于CrodaInc.
7 DeZaan D-11-A,来自于ADM
8 来自于DMV International
9 麦芽糊精10DE(M-100),来自于Grain Processing Corporation
10 调味剂#14896,来自于David Michael and Co.,Inc.
11 调味剂#1967,来自于David Michael and Co.,Inc.
12 调味剂VA03,来自于Virginia Dare Extract Co.,Inc.
制造方法:
在批量处理器中加入约90%所需的水并加热至130-140。在贮槽中加入调味剂。将最初的水经过液化器再循环,保持液化器在1/2和2/3满之间。将除了调味剂之外的上表所列的所有成分按序加到液化器中。在加入油酸乙酯之前加入甘油一酯和甘油二酯。在加入酪蛋白酸钠和脱脂奶粉前加入消沫乳剂。停止液化器。将液化器倒空并用预先量好的20加仑的水冲洗。将来自于处理器的产品通过热交换器、均质器,然后在经过热交换器回到处理器。加热至170(+/-5),在总共4500psi、第二步500psi下均质,然后冷却至45以下。达到这一温度后,增压4分30秒,将此液体装进贮槽中。
当产品水平面在锥形底加工器中下降到1英尺时,将加工器循环4分30秒以使其完全均质。除去均质器的压力。停止加热,用预先称量的占总重量95%的水冲洗系统。混合20分钟,然后取样以便标准化。标准化结束后(所有所需固体)加水至足量。
将饮料送到包装设备中,这里它被装进合适的包装中。这些饮料的包装可经甄式干馏或无菌灭菌的。所需的金属饮料罐,例如在甄式干馏加工中可使用DWI马口铁食品罐(300×315,有18个珠(bead),每罐装12盎司)。“Dole”型金属罐可作为无菌操作的例子。
实施例IV
糖果棒
材料 %w/v
高果糖玉米糖浆 18.0
紫云英蜜 18.0
脱脂花生粉 5.0
分离大豆蛋白1 28.2
脱脂乳粉2 10.0
红糖 6.0
油酸乙酯3 14.0
天然桔子4 0.2
脂肪酸遮盖剂(Masker)5 0.1
天然花生调味剂6 0.1
天然蜂蜜调味剂7 0.1
香草乳蛋糕调味剂8 0.1
大豆磷脂9 0.2
总计 100.0
1 Supro 661,来自于Protein Technologies International
2 低热类型,来自于Agrimark
3 Crodamol EO,来自于Croda,Inc.,或05-58405,来自于Penta ManufacturingCo.
4 调味剂57.458/AP SD,来自于Firmenich
5 调味剂348118,来自于Firmenich
6 调味剂57.304/T,来自于Firmenich
7 调味剂598.513/8,来自于Firmenich
8 调味剂HC600-137,来自于P&G
9 Alcolec S,来自于美国卵磷脂公司
制造方法:
将所有的粉末物质称重并在合适的混合器/搅拌器中预先混合。将高果糖玉米糖浆和蜂蜜称重并在合适的器皿中混合。将糖浆状混合物加热至约90。在大小合适的容器中称量油酸乙酯。将所有的液态调味剂和大豆磷脂称重并加到油酸乙酯中,混合直至均一。在大小合适的混合器(如,Hobart的Sigma刀混合器)中一起加入粉末状混合物,油酸乙酯混合物和糖浆。混合/揉捏直至得到均一的结构。
把批料分成厚片并切成重约57克的棒芯(大约1″宽,″高,3″长)。在棒芯上用牛奶巧克力或其它此类所需包衣混合物涂层或包衣。将包衣的小棒冷却至室温,然后包装。每个小棒中约含8g油酸乙酯。
实施例V
模制片
将棕榈酸和聚烃氧基40氢化蓖麻油熔化,并以4∶1的比例混合。将混合物倒进或熔化进大小合适的片剂模型中,其中,每片片剂中约0.5g棕榈酸。将模型冷却至固化,然后从模型中取出片剂。
实施例VI
软明胶胶囊
用标准的软-明胶条带技术/塑模技术将纯净的亚油酸(工业级)密封在#20椭圆形的软明胶胶囊中,使每个胶囊中约含1克亚油酸。
实施例VII
硬明胶胶囊
用高剪切混合器将油酸(90%)和煅制氧化硅以1∶1的比例混合。用标准的高速胶囊填充机将所得混合物密封在00号的硬明胶胶囊中,使每个胶囊中约含0.4克油酸。
实施例VIII
药物乳剂
成分 重量百分数
油酸乙酯 20.0
三甘醇单油酸酯 3.0
聚山梨醇酯80 2.0
调味剂 0.5
糖精钠 0.2
纯水 适量
总计 100.0
制造方法:
将三甘醇单油酸酯分散在油酸乙酯中。将聚山梨醇酯80溶解在纯水中。用Microfluidizer(Microfluidizer公司)将油和水溶液乳化。搅拌加入调味剂和糖精钠。将乳剂包装入液体包装器皿(如500ml的茶色玻璃瓶)中。
实施例IX
微胶囊
成分 重量百分数
明胶1 33.0
六聚磷酸盐 3.0
二十碳五烯酸 59.9
戊二醛 4.1
1A型,275 Bloom,来自于Knox Gelatin Co.
制造方法:
将约150g明胶溶解在约55℃的纯水中。将约20g六聚磷酸盐溶解在约55℃的纯水中。以约450rpm的转速在氮气覆盖下将二十碳五烯酸乳化在明胶溶液中。在乳液中加入约120g约55℃的纯水,保持约450rpm的搅拌转速。在乳液中加入磷酸盐溶液。用冰醋酸将所得混合物的pH调至3.5-4.5之间。停止加热,继续搅拌让混合物缓慢冷却至室温。再将混合物冷却至约10℃。加入戊二醛并让交联反应发生过夜。用纯水将所得微胶囊冲洗三次并过滤干燥。将所述微胶囊包装进合适的包装物(如小体积的塑料药瓶)中。
Claims (11)
1.一种可在人和动物中引起饱腹感的口服组合物,包括选自胃-肠酶类存在时能水解的长链脂肪酸、它们的非甘油酯、及其混合物的饱腹剂,其中所述的饱腹剂在胃中释放。
2.如权利要求1所述的组合物,其中所述的长链脂肪酸和它们的非甘油酯含有12-24个碳原子并含有0-6个碳-碳双键。
3.如权利要求2所述的组合物,其中,脂肪酸选自月桂酸、月桂烯酸、肉豆蔻酸、肉豆蔻烯酸、十五烷酸、棕榈酸、棕榈油酸、十七烷酸、硬脂酸、二羟硬脂酸、油酸、蓖麻油酸、反油酸、亚油酸、α-亚麻酸、二高γ-亚麻酸、桐酸、里卡利酸、花生四稀酸、花生酸、二十烯酸、二十碳五烯酸、山俞酸、芥子酸、二十二碳六烯酸、二十四酸以及它们的混合物。
4.如权利要求1所述的组合物,其中所述的长链脂肪酸和它们的非甘油酯含有16-18个碳原子并含有0-3个碳-碳双键。
5.如权利要求4所述的组合物,其中所述的脂肪酸选自油酸、亚油酸及其混合物。
6.如权利要求2所述的组合物,其中所述的非甘油脂肪酸酯包括醇酯,其中所述的酯的醇部分选自甲醇、乙醇、正丙醇、异丙醇、正丁醇、异丁醇以及它们的混合物。
7.如权利要求4所述的组合物,其中所述的非甘油脂肪酸酯选自油酸乙酯、亚油酸乙酯及其混合物。
8.如权利要求1所述的组合物,其中,每次给予所述组合物中所述饱腹剂的用量为每千克体重每次施用约0.01克-10.0克。
9.如权利要求8所述的组合物,其中,每次给予所述组合物中所述饱腹剂的用量为每千克体重每次施用约0.04克-1.0克。
10.权利要求1-9中任一项所述的口服组合物在制造控制人和其它动物个体体重的组合物中的用途。
11.权利要求1-9中任一项所述的口服组合物在制造控制个体食欲的组合物中的用途。
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US7025984B1 (en) * | 2000-06-26 | 2006-04-11 | The Procter & Gamble Company | Compositions and methods for body weight management |
US6626644B2 (en) * | 2000-10-30 | 2003-09-30 | Ntn Corporation | Magnetically levitated pump and controlling circuit |
US6429190B1 (en) | 2000-12-15 | 2002-08-06 | Pacifichealth Laboratories, Inc. | Method for extending the satiety of food by adding a nutritional composition designed to stimulate cholecystokinin(CCK) |
US7225486B2 (en) * | 2005-01-10 | 2007-06-05 | Jackson Iii Avery M | Therapeutic seat cushion |
-
2000
- 2000-06-26 US US09/603,626 patent/US7025984B1/en not_active Expired - Lifetime
-
2001
- 2001-06-21 DE DE60119104T patent/DE60119104T2/de not_active Expired - Lifetime
- 2001-06-21 RU RU2003101971/15A patent/RU2301668C2/ru not_active IP Right Cessation
- 2001-06-21 AU AU2001268644A patent/AU2001268644A1/en not_active Abandoned
- 2001-06-21 JP JP2002504835A patent/JP2004501170A/ja active Pending
- 2001-06-21 EP EP01946620A patent/EP1294240B1/en not_active Expired - Lifetime
- 2001-06-21 EP EP06008492A patent/EP1676488A3/en not_active Withdrawn
- 2001-06-21 BR BR0111963-0A patent/BR0111963A/pt not_active IP Right Cessation
- 2001-06-21 NZ NZ522996A patent/NZ522996A/en unknown
- 2001-06-21 MX MXPA03000048A patent/MXPA03000048A/es active IP Right Grant
- 2001-06-21 CA CA002410985A patent/CA2410985C/en not_active Expired - Fee Related
- 2001-06-21 CN CNB018117139A patent/CN100334973C/zh not_active Expired - Fee Related
- 2001-06-21 AT AT01946620T patent/ATE324053T1/de not_active IP Right Cessation
- 2001-06-21 PL PL360185A patent/PL202686B1/pl not_active IP Right Cessation
- 2001-06-21 WO PCT/US2001/019828 patent/WO2002000042A2/en active IP Right Grant
- 2001-06-25 PE PE2001000617A patent/PE20020112A1/es not_active Application Discontinuation
- 2001-06-25 AR ARP010103006A patent/AR029687A1/es unknown
-
2002
- 2002-11-28 ZA ZA200209662A patent/ZA200209662B/en unknown
-
2005
- 2005-05-03 US US11/120,853 patent/US8287898B2/en not_active Expired - Fee Related
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2008
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
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EP0003407A1 (en) * | 1978-01-23 | 1979-08-08 | Efamol Limited | Pharmaceutical and dietary composition comprising gamma-linolenic acids |
WO1987003198A1 (en) * | 1985-11-25 | 1987-06-04 | Aco Läkemedel Ab | Use of a hydrophobic substance for preparing an enteric preparation for treatment of obesity and an enteric preparation |
US5665384A (en) * | 1990-04-06 | 1997-09-09 | Rhone-Poulenc Rorer S.A. | Oily capsules of ketoprofen |
US6034132A (en) * | 1998-01-05 | 2000-03-07 | Natural Nutrition Ltd. As | Method of reducing bodyweight and treating obesity |
Also Published As
Publication number | Publication date |
---|---|
AU2001268644A1 (en) | 2002-01-08 |
US8287898B2 (en) | 2012-10-16 |
US20050197395A1 (en) | 2005-09-08 |
EP1676488A3 (en) | 2013-02-20 |
WO2002000042A2 (en) | 2002-01-03 |
WO2002000042A3 (en) | 2002-04-04 |
CN1452461A (zh) | 2003-10-29 |
ATE324053T1 (de) | 2006-05-15 |
DE60119104D1 (de) | 2006-06-01 |
US7025984B1 (en) | 2006-04-11 |
BR0111963A (pt) | 2003-05-13 |
EP1294240B1 (en) | 2006-04-26 |
PL360185A1 (en) | 2004-09-06 |
RU2301668C2 (ru) | 2007-06-27 |
DE60119104T2 (de) | 2006-11-30 |
ZA200209662B (en) | 2003-10-23 |
EP1676488A2 (en) | 2006-07-05 |
NZ522996A (en) | 2004-10-29 |
CA2410985A1 (en) | 2002-01-03 |
JP2004501170A (ja) | 2004-01-15 |
JP2009132684A (ja) | 2009-06-18 |
AR029687A1 (es) | 2003-07-10 |
PE20020112A1 (es) | 2002-03-14 |
CA2410985C (en) | 2008-04-15 |
PL202686B1 (pl) | 2009-07-31 |
EP1294240A2 (en) | 2003-03-26 |
MXPA03000048A (es) | 2004-07-08 |
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