CN111107844A - 包含体脂减少助剂及β-葡聚糖作为有效成分的肥胖预防或治疗用组合物 - Google Patents
包含体脂减少助剂及β-葡聚糖作为有效成分的肥胖预防或治疗用组合物 Download PDFInfo
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- CN111107844A CN111107844A CN201880060863.4A CN201880060863A CN111107844A CN 111107844 A CN111107844 A CN 111107844A CN 201880060863 A CN201880060863 A CN 201880060863A CN 111107844 A CN111107844 A CN 111107844A
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Abstract
本发明涉及包含体脂减少助剂及β‑葡聚糖(β‑glucan)作为有效成分的肥胖预防或治疗用组合物。
Description
技术领域
本发明涉及包含体脂减少助剂及β-葡聚糖(尤其,来源于裂褶菌的β-葡聚糖)作为有效成分的肥胖预防或治疗用组合物。
背景技术
肥胖是指体脂的过度增加和由此诱发代谢异常的状态。肥胖视为高血压、糖尿、心血管疾病之类的多种成人病和癌等的主要危险因素。与其他国家一样,韩国成人的肥胖患病率最近20年处于不断增加的趋势。自多年前,世界卫生组织(WHO)作为“21世纪新型传染病”,美国医学会将肥胖规定为“疾病”。这种世界动向启示肥胖是需要治疗的“疾病”,而不再是单纯的美容、身体现象问题。在韩国,最近,也随着医疗及制药部门的努力,处于形成政府方面进行肥胖运动等用于解决肥胖的动向的趋势。与多个医疗发达国家一样,韩国国民也形成提高对肥胖的警惕性,并将肥胖规定为疾病的认识。据报告,肥胖与第二型糖尿病、心血管疾病、骨关节炎、部分癌、睡眠呼吸暂停症、哮喘和非酒精性脂肪肝具有相关性。抗肥胖药物治疗目的不仅是为了减少体重,而且,更重要的是,改善与肥胖相关的高血糖、血脂异常症、动脉硬化性心脏病等的多种伴随疾病。
当前,肥胖的治疗方法有化学疗法(减肥助剂)。2006年某一消费者团体实施的问卷调查结果指出首尔市民的过半数左右服用保健品,这是因为以吃的方式解决比维持健康的生活习惯更容易接受。现实中,对于肥胖,服用看似比难的饮食疗法和身体活动增加、规律性运动更有效的保健品更容易。因此,减肥助剂在现代肥胖治疗中是必不可少的。可常见的减肥助剂主要包含藤黄果提取物(羟基柠檬酸(HCA))、共轭亚油酸(CLA)、膳食纤维等的成分。每个助剂都有所差异,但指出对抑制食欲和抑制脂肪积累、产生热、减少体脂等有效,而未具备这种效果的依据资料,且据报告还有对于副作用的研究结果,这是化学疗法的最大问题。共轭亚油酸,即,CLA作为Conjugated Linoleic Acid的简称,1998年在美国第一次以减肥食品进行销售,在韩国,2006年6月,(株)HK生物技术最初从食品的药品安全厅以保健食品个别认定型产品被承认之后,随着在几家企业被追加承认,在电视购物等中使用的频率增多。有明确结果指出共轭亚油酸在动物研究中预防体重的增加,并抑制脂肪积累,但作为副作用出现胰岛素抵抗性和脂肪肝。在肝中认识到胰岛素的增加,并终止葡萄糖的生产来诱导葡萄糖的分解,当胰岛素抵抗性增加时,不出现这种作用,从而诱发第二型糖尿病。在临床实验中,腹部肥胖者在摄取共轭亚油酸之后,也出现体重和体脂减少,但也出现胰岛素抵抗性增加,高血糖和HDL-胆固醇减少的副作用。在最近研究结果中指出可诱导至急性肝炎,也指出共轭亚油酸具有使肝损伤的肝毒性。
因此,当前,作为全世界使用的体脂量减少助剂的共轭亚油酸对体脂量减少的效果得到证明,但诱发肝毒性的副作用未得到解决。最近,随着肥胖人口的增加,对减肥的关注度变高,从而开发多种减肥食品,随着减肥相关市场大大成长,解决减肥产品的副作用成为很紧迫的问题。
β-葡聚糖作为葡萄糖以β-1,3化学键为中心聚合的多糖类,有从蘑菇、酵母等的微生物的细胞壁或细胞的多糖类分离来生产的来源于微生物的β-葡聚糖(β-1,3-葡聚糖或β-1,3-1,6-葡聚糖)和从大麦、燕麦之类的谷物的膳食纤维提取来生产的植物性β-葡聚糖(β-1,3-1,4-葡聚糖)。这些可根据更具体的葡萄糖结合结构来呈现多种生物活性,并且,作为高附加价值的生物材料,多样地利用化妆品的添加剂、保健品、食品添加剂、混凝土外加剂、饲料添加剂等。
尤其,众所周知,存在于裂褶菌(Schizophyllum commune)的裂褶菌多糖(Schizophyllan)等的β-(1,6)-分支的(1,3)-葡聚糖(glucan)的形态的β-葡聚糖(β-Glucan)增强免疫力,同时与无耐性的天然免疫调节剂报告有对于抗癌及抗氧化的生物活性等。众所周知,β-葡聚糖为作用于人体的免疫系统来增强人体的免疫力的所谓的生物反应调节剂(BRM,biological response modifiers),尤其,据报告,β-葡聚糖激活免疫系统内的巨噬细胞(macrophage)的功能来使这种巨噬细胞分泌作为其他淋巴细胞或白细胞的增殖因子的干扰素或白细胞介素等的细胞因子,从而强化免疫系统的整体功能。并且,确认到即使因作为抗肿瘤剂的紫杉醇而使肝损伤,β-葡聚糖也抑制坏死过程来保护肝,据报告,从农杆菌(Agrobacterium spZX09)分离的水溶性的β-葡聚糖也在因乙醇而使肝损伤时保护肝。由此,确认到在肝损伤的危险中可起到保护肝的作用。
发明内容
技术问题
本发明提供用于抑制由于体脂减少助剂引起的副作用的包含体脂减少助剂及β-葡聚糖(β-glucan)作为有效成分的肥胖预防或治疗用药学组合物等。
但是,本发明所要实现的技术问题不局限于以上提及的问题,本发明所属技术领域的普通技术人员可从以下记载内容中明确地理解未提及的其他多个问题。
解决问题的方案
本发明提供包含体脂减少助剂及β-葡聚糖(β-glucan)作为有效成分的肥胖预防或治疗用药学组合物。
上述组合物可用于抑制体脂减少助剂引起的副作用。
上述副作用可以为肝毒性或血中胆固醇含量增加引起的副作用。
上述体脂减少助剂可以为选自由共轭亚油酸、藤黄果提取物及膳食纤维组成的组中的一种以上,优选地,可以为共轭亚油酸。
上述β-葡聚糖可从裂褶菌(Schizophyllum commune)或其的培养物分离。
上述β-葡聚糖可具有β-(1,6)-分支的(1,3)-葡聚糖的结构。
上述体脂减少助剂及上述β-葡聚糖能够以2:1(w/v:w/v)至100:1(w/v:w/v)的比例进行混合。
作为本发明的一实例,提供包含体脂减少助剂及β-葡聚糖(β-glucan)作为有效成分的肥胖预防或改善用保健食品。
作为本发明的再一实例,提供用于将体脂减少助剂及β-葡聚糖(β-glucan)使用于肥胖预防或治疗用药学组合物的用途。
作为本发明的另一实例,提供用于将体脂减少助剂及β-葡聚糖(β-glucan)使用于肥胖预防或改善用保健食品的用途。
作为本发明的还一实例,提供包括将体脂减少助剂及β-葡聚糖(β-glucan)给药到个体的步骤的肥胖治疗方法。
发明的效果
本发明涉及包含体脂减少助剂及β-葡聚糖(β-glucan)作为有效成分的肥胖预防或治疗用组合物,上述组合物不仅具有上述体脂减少助剂的协同效应,还具有可抑制上述体脂减少助剂引起的副作用,即,肝毒性,并抑制血中胆固醇含量增加的优点。
因此,根据本发明的组合物,可实现对生物体安全的体脂减少,从而期待对肥胖预防或治疗有用。
附图说明
图1为比较在实验组1-1至实验组1-2、比较实验组1-1至比较实验组1-3中将投入药物开始给药的28周后小鼠的照片。
图2为比较在实验组1-1至实验组1-2、比较实验组1-1至比较实验组1-3中将投入药物开始给药之后,测定28周期间每周重量的结果的曲线图。
图3为牺牲在实验组1-1至实验组1-2、比较实验组1-1至比较实验组1-3中将投入药物开始给药的28周后小鼠之后,测定重量及组织重量的结果的比较表。
图4为牺牲在实验组1-1至实验组1-2、比较实验组1-1至比较实验组1-3中将投入药物开始给药的28周后小鼠之后,执行血清分析的结果的比较表。
图5为比较在实验组2-1至实验组2-2、比较实验组2-1至比较实验组2-3中将投入药物开始给药之后,测定20周期间每周重量的结果的曲线图。
图6为牺牲在实验组2-1至实验组2-2、比较实验组2-1至比较实验组2-3中将投入药物开始给药的20周后小鼠之后,测定重量及组织重量的结果的比较表。
图7为牺牲在实验组2-1至实验组2-2、比较实验组2-1至比较实验组2-3中将投入药物开始给药的20周后小鼠之后,执行血清分析的结果的比较表。
具体实施方式
本发明人为了克服体脂减少助剂引起的副作用而努力,最终,确认到当在其中将来源于裂褶菌的β-葡聚糖并行给药时,与将体脂减少助剂单独给药的情况相比,不仅增近重量减少效果,还可抑制肝毒性,抑制血中胆固醇含量增加,并完成本发明。另一方面,确认到当将来源于裂褶菌的β-葡聚糖单独给药时,不具有显著的重量减少效果。
以下,详细说明本发明。
肥胖预防或治疗用药学组合物
本发明提供包含体脂减少助剂及β-葡聚糖(β-glucan)作为有效成分的肥胖预防或治疗用药学组合物。
本发明的肥胖预防或治疗用药学组合物的特征在于,包含体脂减少助剂及β-葡聚糖作为有效成分。
上述组合物用于肥胖预防或治疗,其可通过测定重量及组织重量进行确认,或通过甘油三酯含量及游离脂肪酸含量分析进行确认。
并且,上述组合物可用于抑制体脂减少助剂引起的副作用,具体地,上述副作用可以为肝毒性或血中胆固醇含量增加引起的副作用。更具体地,上述肝毒性可通过测定肝的重量进行确认,或通过GOT/AST数值及γ-GPT/ALT数值分析进行确认。
上述体脂减少助剂可以为选自由共轭亚油酸、藤黄果提取物及膳食纤维组成的组中的一种以上,优选地,可以为共轭亚油酸或藤黄果提取物。当将上述共轭亚油酸或藤黄果提取物单独给药时,减少体脂来具有重量减少效果,但导致肝毒性及血中胆固醇含量增加引起的副作用的副作用成为问题。
另一方面,上述β-葡聚糖为了抑制上述体脂减少助剂引起的副作用而并行给药,优选地,具有β-(1,6)-分支的(1,3)-葡聚糖的结构,但不局限于此。上述β-葡聚糖可来源于微生物菌体、酵母菌体或蘑菇菌丝体,更具体地,可从裂褶菌(Schizophyllum commune)或其的培养物分离,但不局限于此。
为了从裂褶菌分离上述β-葡聚糖,可从以液态方式培养的培养物得到裂褶菌菌丝体。更具体地,根据韩国授权专利第10-0892355号或韩国授权专利第10-0909857号中所公知,培养裂褶菌,并从其的培养物分离及得到β-葡聚糖,这是更优选的,但不局限于此。
当混合包含上述体脂减少助剂的第一溶液及包含上述β-葡聚糖的第二溶液来并用给药时,优选地,上述体脂减少助剂及上述β-葡聚糖以2:1(w/v:w/v)至100:1(w/v:w/v)的比例进行混合,更优选地,上述体脂减少助剂及上述β-葡聚糖以2:1(w/v:w/v)至10:1(w/v:w/v)的比例进行混合,但不局限于此。此时,当体脂减少助剂的浓度过小时,存在重量减少效果微弱的问题,当β-葡聚糖的浓度过小时,存在无法有效抑制肝毒性或血中总胆固醇含量增加的问题。
另一方面,当将上述体脂减少助剂及上述β-葡聚糖以2:1(w/v:w/v)至100:1(w/v:w/v)的比例进行混合来提高β-葡聚糖的浓度时,具有可更有效抑制肝毒性及血中总胆固醇含量增加的优点。
本发明的肥胖预防或治疗用药学组合物可分别根据通常的方法来以散剂、颗粒剂、片剂、胶囊剂、悬浮液、乳液、糖浆、气溶胶等的口服剂剂型、外用剂、栓剂及灭菌注射溶液的形态进行剂型化而使用,为了剂型化,可包含通常用于制备药学组合物的适当的载体、赋形剂或稀释剂。
作为上述载体或赋形剂或稀释剂,可例举包含乳糖、葡萄糖、蔗糖、山梨糖醇、甘露醇、木糖醇、赤藓糖醇、麦芽糖醇、淀粉、阿拉伯胶、海藻酸盐、明胶、磷酸钙、硅酸钙、纤维素、甲基纤维素、微晶纤维素、聚乙烯吡咯烷酮、水、羟基苯甲酸甲酯、羟基苯甲酸丙酯、滑石、硬脂酸镁及矿物油等的多种化合物或混合物。
当进行制剂化时,可利用通常使用的填充剂、重量剂、结合剂、湿润剂、崩解剂、表面活性剂等的稀释剂或赋形剂来进行制备。
用于口服给药的固体制剂可通过在上述体脂减少助剂及上述β-葡聚糖中混合至少一种的赋形剂,例如,淀粉、硼酸钙、蔗糖或乳糖、明胶等来进行制备。并且,除了单纯的赋形剂之外,还可使用硬脂酸镁、滑石之类的润滑剂。
作为用于口服的液态制剂,有悬浮液、内服溶液剂、乳剂、糖浆剂等,除了作为常使用的单纯稀释剂的水、液体石蜡之外,可包含多种赋形剂,例如,湿润剂、甜味剂、芳香剂、保鲜剂等。
用于非口服给药的制剂包含灭菌的水溶液、非水性溶剂、悬浮剂、乳剂、冷冻干燥制剂、栓剂。作为非水性溶剂、悬浮剂,可使用丙二醇、聚乙二醇、橄榄油之类的植物油、油酸乙酯之类的可注射的酯等。作为栓剂的基剂,可使用威泰索尓(witepsol)、聚乙二醇、吐温(tween)61、可可脂、月桂酯、甘油明胶等。
本发明的肥胖预防或治疗用药学组合物的优选给药量可根据患者的状态、体重、疾病的程度、药物形态、给药途径及期间而不同,但可由本发明所属技术领域的普通技术人员适当地进行选择。但是,为了优选效果,可用β-葡聚糖以一天0.0001μg/kg至400mg/kg进行给药,更优选地,以0.001至200mg/kg进行给药。可一天一次进行给药,也可分多次进行给药。只是,本发明的范围不局限于上述给药量。
本发明的肥胖预防或治疗用药学组合物能够以多种途径给药到大鼠、小鼠、家畜、人类等的哺乳动物。作为给药的所有方式,例如,可通过口服、直肠或静脉、肌肉、皮下、子宫内硬膜或脑血管内(intracerebroventricular)注射来进行给药。
肥胖预防或改善用保健食品
并且,本发明提供包含体脂减少助剂及β-葡聚糖作为有效成分的肥胖预防或改善用保健食品。
本发明的肥胖预防或改善用保健食品包含体脂减少助剂及β-葡聚糖作为有效成分,上述体脂减少助剂及上述β-葡聚糖的说明如上所述。
在本发明的肥胖预防或改善用保健食品中,当将上述体脂减少助剂及上述β-葡聚糖用作保健食品的添加物时,可将其直接添加或与其他食品或食品成分一同使用,可根据通常的方法来适当地使用。有效成分的混合量可根据预防、健康或治疗等的各个使用目的来适当地确定。
作为保健食品的剂型,除了散剂、颗粒剂、丸、片剂、胶囊剂的形态之外,还可采用通常的食品或饮料的形态。
上述食品的种类不受特别限制,可添加上述物质的食品的例有肉类、香肠、面包、巧克力、糖果类、小吃类、饼干类、披萨、拉面、其他面类、口香糖类、包含冰淇淋类的酪农产品、各种汤、饮料、茶、补液、酒精饮料及维生素复合剂等,可全部包含通常含义的食品。
通常,当制备食品或饮料时,相对于100重量份的原料,能够以15重量份以下,优选地,以10重量份以下的量添加上述体脂减少助剂及上述β-葡聚糖。但是,当以健康及卫生为目的或以调节健康为目的长时间摄取时,上述量可以为上述范围以下,并且,在本发明中,利用天然物,从而在安全性方面不存在问题,因而还能够以上述范围以上的量使用。
本发明的保健食品中的饮料可如同通常的饮料包含多种调味剂或天然碳水化合物等作为追加成分。上述的天然碳水化合物可以为葡萄糖、果糖之类的单糖、麦芽糖、蔗糖之类的二糖及糊精、环糊精之类的多糖、木糖醇、山梨糖醇、赤藓糖醇等的糖醇。作为甜味剂,可使用索马甜、甜叶菊提取物之类的天然甜味剂或糖精、阿斯巴甜之类的合成甜味剂等。在本发明的每100mL的饮料中,上述天然碳水化合物的比例可以为约0.01~0.04g,优选为约0.02~0.03g。
除了上述物质之外,本发明的肥胖预防或改善用保健食品可包含多种营养剂、维生素、电解质、风味剂、着色剂、果胶酸及其盐、海藻酸及其盐、有机酸、保护性胶体增稠剂、pH调节剂、稳定剂、防腐剂、甘油、酒精、碳酸饮料中使用的碳酸化剂。除此之外,本发明的睡眠改善用组合物可包含用于天然果汁、果汁饮料及蔬菜饮料的果肉。这种成分可独立或混合使用。这种添加剂的比例不受限制,但通常,相对于100重量份的本发明的保健食品,在0.01~0.1重量份的范围内进行选择。
进而,本发明提供用于将体脂减少助剂及β-葡聚糖(β-glucan)使用于肥胖预防或治疗用药学组合物的用途。
并且,本发明提供用于将体脂减少助剂及β-葡聚糖(β-glucan)使用于肥胖预防或改善用保健食品的用途。
并且,本发明提供包括将体脂减少助剂及β-葡聚糖(β-glucan)给药到个体的步骤的肥胖治疗方法。
在本发明中,“个体”是指需要治疗疾病的对象,更具体地,是指人类或非-人类的灵长类、小鼠(mouse)、大鼠(rat)、狗、猫、马及牛等的哺乳类。
如上所述,本发明涉及包含体脂减少助剂及β-葡聚糖(β-glucan)作为有效成分的肥胖预防或治疗用组合物,上述组合物不仅具有上述体脂减少助剂的协同效应,还具有可抑制上述体脂减少助剂引起的副作用,即,肝毒性,并抑制血中胆固醇含量增加的优点。
因此,根据本发明的组合物,可减少对生物体安全的体脂,从而期待有用于肥胖预防或治疗。
以下,为了有助于理解本发明,提出优选实施例。但是,以下实施例仅用于更加容易理解本发明,本发明的内容不局限于以下实施例。
实施例
实施例1:在共轭亚油酸(CLA)中将β-葡聚糖并行给药来得到的体脂减少助剂的协
同效应及副作用抑制效果的确认(动物实验)
购买作为体脂量监视对象的6周龄的野生型C57BL/6小鼠,并饲养3天来使其适应环境之后,进行饲养。具体地,以每组6只的方式将小鼠分为共5组,并如表1中所示,作为投入药物,以每天1次的方式将共轭亚油酸(CLA)(制造商:西格玛奥德里奇)、来源于裂褶菌的β-葡聚糖(β-(1,6)-分支的(1,3)-葡聚糖的结构)(裂褶菌多糖(SPG))(制造商:贵真生物技术)及磷酸盐缓冲液(PBS,Phosphate buffer solution)并行或单独进行口服给药。具体地,在实验组1-1中,将0.2ml的共轭亚油酸(浓度=10mg/ml)进行口服给药,经过30分钟之后,将0.2ml的来源于裂褶菌的β-葡聚糖(具有β-(1,6)-分支的(1,3)-葡聚糖的结构的裂褶菌多糖)(浓度=0.4mg/ml)进行口服给药。并且,在实验组1-2中,将0.2ml的共轭亚油酸(浓度=10mg/ml)进行口服给药,经过30分钟之后,将0.2ml的来源于裂褶菌的β-葡聚糖(具有β-(1,6)-分支的(1,3)-葡聚糖的结构的裂褶菌多糖)(浓度=2mg/ml)进行口服给药。另一方面,在比较实验组1-1中,将0.2ml的共轭亚油酸(浓度=10mg/ml)进行口服给药。并且,在比较实验组1-2中,将0.2ml的来源于裂褶菌的β-葡聚糖(具有β-(1,6)-分支的(1,3)-葡聚糖的结构的裂褶菌多糖)(浓度=2mg/ml)进行口服给药,在比较实验组1-3中,将0.2ml的磷酸盐缓冲液(PBS,Phosphate buffer solution)进行口服给药。
表1
将对于各个给药组的28周后的实验动物的最终结果示于图1中。此时,在体脂量增加的动物模型中,确认是否通过将作为体脂减少助剂的共轭亚油酸及β-葡聚糖并行口服给药,呈现体脂减少助剂的协同效应及副作用抑制效果。
具体地,在实验组1-1至实验组1-2、比较实验组1-1至比较实验组1-3中,开始将投入药物进行给药之后,测定28周期间每周重量,并将其结果示于图2中。
如图2所示,在比较实验组1-1中,确认到随着投入药物给药期间的经过,与比较实验组1-3相比,重量大大减少,但在比较实验组1-2中,确认到随着投入药物给药期间的经过,与比较实验组1-3相比,几乎不发生重量变化。另一方面,在将共轭亚油酸和裂褶菌多糖并用给药的实验组1-1至实验组1-2中,确认到随着投入药物给药时间的经过,与将共轭亚油酸单独给药的比较实验组1-1相比,重量更加减少。即,确认到体脂减少助剂(共轭亚油酸)的协同效应。尤其,在实验组1-2中,确认到随着投入药物给药期间的经过,与实验组1-1相比,重量大大减少。
并且,在实验组1-1至实验组1-2、比较实验组1-1至比较实验组1-3中,牺牲开始将投入药物进行给药的28周后小鼠之后,测定重量及组织重量,并将其结果示于图3中。
如图3所示,在将作为体脂减少助剂的共轭亚油酸口服给药的实验组1-1至实验组1-2及比较实验组1-1中,确认到与比较实验组1-3相比,重量及各个器官的组织重量大大减少。只是,在比较实验组1-1中,确认到肝的组织重量反而增加。即,这被视为作为体脂减少助剂的共轭亚油酸因肝毒性引起的副作用而导致。在比较实验组1-2中,确认到与比较实验组1-3相比,重量及各个期间的组织重量几乎不发生变化。
另一方面,在实验组1-1至实验组1-2中,确认到与比较实验组1-1相比,更加减少重量,但肝的组织重量反而减少。除此之外,确认到在脾脏、肾脏、心脏、肌肉的组织重量没有大的差异。
并且,在实验组1-1至实验组1-2、比较实验组1-1至比较实验组1-3中,牺牲开始将投入药物进行给药的28周后小鼠之后,执行血清分析,并将其结果示于图4中。
如图4所示,在将作为体脂减少助剂的共轭亚油酸进行口服给药的实验组1-1至实验组1-2及比较实验组1-1中,竟然确认到与比较实验组1-3相比,甘油三酯及游离脂肪酸含量减少一半以上。只是,在比较实验组1-1中,确认到与比较实验组1-3相比,血中总胆固醇含量增加,且具有肝损伤。这可被视为作为体脂减少助剂的共轭亚油酸增加血中总胆固醇含量,且如已在图3中所示,导致肝毒性(例如,肝重量增加)引起的副作用。
另一方面,在将裂褶菌多糖并用给药的实验组1-1至实验组1-2中,可确认到与比较实验组1-1或比较实验组1-3相比,可大大降低血中总胆固醇含量,并将肝毒性最小化。尤其,在实验组1-2中,确认到与比较实验组1-2相比,总血中胆固醇含量也大大降低,并确认到随着β-葡聚糖的含量增加,总血中胆固醇含量及肝毒性更加降低。
实施例2:在藤黄果提取物(羟基柠檬酸)中将β-葡聚糖并行给药来得到的体脂减
少助剂的协同效应及副作用抑制效果的确认(动物实验)
购买作为体脂量监视对象的6周龄的野生型C57BL/6小鼠,并饲养3天来使其适应环境之后,进行饲养。具体地,以每组10只的方式将小鼠分为共5组,如表2中所示,作为投入药物,以每天1次的方式将藤黄果提取物(羟基柠檬酸)(制造商:西格玛奥德里奇)、来源于裂褶菌的β-葡聚糖(β-(1,6)-分支的(1,3)-葡聚糖的结构)(裂褶菌多糖)(制造商:贵真生物技术)及磷酸盐缓冲液(PBS,Phosphate buffer solution)并行或单独进行口服给药。具体地,在实验组2-1中,将0.2ml的羟基柠檬酸(浓度=10mg/ml)进行口服给药,经过30分钟之后,将0.2ml的来源于裂褶菌的β-葡聚糖(具有β-(1,6)-分支的(1,3)-葡聚糖的结构的裂褶菌多糖)(浓度=0.4mg/ml)进行口服给药。并且,在实验组2-2中,将0.2ml的羟基柠檬酸(浓度=10mg/ml)进行口服给药,经过30分钟之后,将0.2ml的来源于裂褶菌的β-葡聚糖(具有β-(1,6)-分支的(1,3)-葡聚糖的结构的裂褶菌多糖)(浓度=2mg/ml)进行口服给药。另一方面,在比较实验组2-1中,将0.2ml的羟基柠檬酸(浓度=10mg/ml)进行口服给药。并且,在比较实验组2-2中,将0.2ml的来源于裂褶菌的β-葡聚糖(具有β-(1,6)-分支的(1,3)-葡聚糖的结构的裂褶菌多糖)(浓度=2mg/ml)进行口服给药,在比较实验组2-3中,将0.2ml的磷酸盐缓冲液(PBS,Phosphate buffer solution)进行口服给药。
表2
此时,在体脂量增加的动物模型中,确认是否通过将作为体脂减少助剂的藤黄果提取物及β-葡聚糖并行口服给药,呈现体脂减少助剂的协同效应及副作用抑制效果。
具体地,在实验组2-1至实验组2-2、比较实验组1-1至比较实验组1-3中,开始将投入药物进行给药之后,测定20周期间每周重量,并将其结果示于图5中。
如图5所示,在比较实验组2-1中,确认到随着投入药物给药期间的经过,与比较实验组2-3相比,重量大大减少,但在比较实验组2-2中,确认到随着投入药物给药期间的经过,与比较实验组2-3相比,几乎不发生重量变化。另一方面,在将羟基柠檬酸和裂褶菌多糖并用给药的实验组2-1至实验组2-2中,确认到随着投入药物给药时间的经过,与将羟基柠檬酸单独给药的比较实验组2-1相比,重量更加减少。即,确认到体脂减少助剂(羟基柠檬酸)的协同效应。尤其,在实验组2-2中,确认到随着投入药物给药期间的经过,与实验组2-1相比,重量大大减少。
并且,在实验组2-1至实验组2-2、比较实验组2-1至比较实验组2-3中,牺牲开始将投入药物进行给药的20周后小鼠之后,测定重量及组织重量,并将其结果示于图6中。
如图6所示,在将作为体脂减少助剂的藤黄果提取物口服给药的实验组2-1至实验组2-2及比较实验组2-1中,确认到与比较实验组2-3相比,重量及各个器官的组织重量大大减少。只是,在比较实验组2-1中,确认到肝的组织重量反而增加。即,这被视为作为体脂减少助剂的藤黄果提取物因肝毒性引起的副作用而导致。在比较实验组2-2中,确认到与比较实验组2-3相比,重量及各个期间的组织重量几乎不发生变化。
另一方面,在实验组2-1至实验组2-2中,确认到与比较实验组2-1相比,更加减少重量,但肝的组织重量反而减少。除此之外,确认到在脾脏、肾脏、心脏、肌肉的组织重量没有大的差异。
并且,在实验组2-1至实验组2-2、比较实验组2-1至比较实验组2-3中,牺牲开始将投入药物进行给药的20周后小鼠之后,执行血清分析,并将其结果示于图7中。
如图7所示,在将作为体脂减少助剂的藤黄果提取物进行口服给药的实验组2-1至实验组2-2及比较实验组2-1中,竟然确认到与比较实验组2-3相比,甘油三酯及游离脂肪酸含量减少一半左右或一半以上。只是,在比较实验组2-1中,确认到与比较实验组2-3相比,血中总胆固醇含量增加,且具有肝损伤。这可被视为作为体脂减少助剂的藤黄果提取物增加血中总胆固醇含量,且如已在图6中所示,导致肝毒性(例如,肝重量增加)引起的副作用。
另一方面,在将裂褶菌多糖并用给药的实验组2-1至实验组2-2中,可确认到与比较实验组1-1或比较实验组1-3相比,可大大降低血中总胆固醇含量,并将肝毒性最小化。尤其,在实验组2-1至实验组2-2中,确认到与比较实验组2-2相比,总血中胆固醇含量大大降低,并确认到随着β-葡聚糖的含量增加,总血中胆固醇含量及肝毒性更加降低。
以下,说明包含本发明的化合物的组合物的制剂例,但本发明仅用于具体说明,而不是对其进行限制。
制剂例1:散剂的制备
400mg的体脂减少助剂及20mg的β-葡聚糖
100mg的乳糖水化物
10mg的滑石
混合上述的多种成分,并填充于气密布来制备散剂。
制剂例2:片剂的制备
100mg的体脂减少助剂及20mg的β-葡聚糖
100mg的玉米淀粉
100mg的乳糖水化物
2mg的硬脂酸镁
混合上述的成分之后,按照通常的片剂的制备方法进行压片来制备片剂。
制剂例3:胶囊剂的制备
100mg的体脂减少助剂及20mg的β-葡聚糖
3mg的微晶纤维素
14.8mg的乳糖水化物
0.2mg的硬脂酸镁
混合上述的成分之后,按照通常的胶囊剂的制备方法填充于明胶胶囊来制备胶囊剂。
制剂例4:注射剂的制备
50mg的体脂减少助剂及10mg的β-葡聚糖
180mg的甘露醇
2974mg的注射用灭菌蒸馏水
26mg的磷酸一氢钠
混合上述的成分之后,按照通常的注射剂的制备方法以上述的成分含量将每1安瓿(2mL)进行制备。
制剂例5:液剂的制备
100mg的体脂减少助剂及10mg的β-葡聚糖
10g的异构糖
5g的甘露醇
适量的纯化水
适量的柠檬香
对于上述的成分,按照通常的制备方法在纯化水中添加各自的成分来进行溶解,并添加适量的柠檬香之后,添加纯化水来调节成共100mL之后进行灭菌,从而填充于褐色瓶来制备液剂。
制剂例6:保健食品的制备
800mg的体脂减少助剂及40mg的β-葡聚糖
适量的维生素混合物
70μg的维生素A醋酸酯
1.0mg的维生素E
0.13mg的维生素B1
0.15mg的维生素B2
0.5mg的维生素B6
0.2μg的维生素B12
10mg的维生素C
10μg的生物素
1.7mg的烟酰胺
50μg的叶酸
0.5mg的泛酸钙
适量的无机质混合物
1.75mg的硫酸亚铁
0.82mg的氧化锌
25.3mg的碳酸镁
15mg的磷酸二氢钾
55mg的磷酸氢二钙
90mg的柠檬酸钾
100mg的碳酸钙
24.8mg的氯化镁
在上述的维生素及矿物混合物的组成比中,将比较适合保健食品的成分混合组成为优选实施例,但也可任意改变其调配比,可按照通常的保健食品制备方法混合上述的成分之后,制备颗粒,并按照通常的方法用于保健食品的制备。
制剂例7:健康饮料的制备
400mg的体脂减少助剂及10mg的β-葡聚糖
15g的维生素C
100g的维生素E(粉末)
19.75g的乳酸亚铁
3.5g的氧化锌
3.5g的烟酰胺
0.2g的维生素A
0.25g的维生素B1
0.3g的维生素B2
定量的纯化水
按照通常的健康饮料制备方法混合上述的成分之后,在85℃温度下搅拌加热约1小时,之后,过滤制成的溶液来取得,并放入灭菌的2l的容器来进行密封灭菌之后进行冷藏保管,之后,用于本发明的健康饮料组合物的制备。
在上述组成比中,将比较适合嗜好饮料的成分混合组成为优选实施例,但也可根据需求阶层或需求国家、使用用途等区域性、民族性嗜好度任意改变其调配比。
上述的本发明的说明用于例示,本发明所属技术领域的普通技术人员应当理解可在不变更本发明的技术思想或必要特征的情况下以其他具体的形态容易变形。因此,应当仅理解为以上记述的实施例在所有方面是例示性的,而非限定。
Claims (12)
1.一种肥胖预防或治疗用药学组合物,其特征在于,包含体脂减少助剂及β-葡聚糖作为有效成分。
2.根据权利要求1所述的肥胖预防或治疗用药学组合物,其特征在于,上述肥胖预防或治疗用药学组合物用于抑制体脂减少助剂引起的副作用。
3.根据权利要求2所述的肥胖预防或治疗用药学组合物,其特征在于,上述副作用为肝毒性或血中总胆固醇含量增加引起的副作用。
4.根据权利要求1所述的肥胖预防或治疗用药学组合物,其特征在于,上述体脂减少助剂为选自由共轭亚油酸、藤黄果提取物及膳食纤维组成的组中的一种以上。
5.根据权利要求4所述的肥胖预防或治疗用药学组合物,其特征在于,上述体脂减少助剂为共轭亚油酸或藤黄果提取物。
6.根据权利要求1所述的肥胖预防或治疗用药学组合物,其特征在于,上述β-葡聚糖从裂褶菌或其的培养物分离。
7.根据权利要求1所述的肥胖预防或治疗用药学组合物,其特征在于,上述β-葡聚糖具有β-(1,6)-分支的(1,3)-葡聚糖的结构。
8.根据权利要求1所述的肥胖预防或治疗用药学组合物,其特征在于,上述体脂减少助剂及上述β-葡聚糖以2:1(w/v:w/v)至100:1(w/v:w/v)的比例进行混合。
9.一种肥胖预防或改善用保健食品,其特征在于,包含体脂减少助剂及β-葡聚糖作为有效成分。
10.一种用途,其特征在于,用于将体脂减少助剂及β-葡聚糖使用于肥胖预防或治疗用药学组合物。
11.一种用途,其特征在于,用于将体脂减少助剂及β-葡聚糖使用于肥胖预防或改善用保健食品。
12.一种肥胖治疗方法,其特征在于,包括将体脂减少助剂及β-葡聚糖给药到个体的步骤。
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KR20170120338 | 2017-09-19 | ||
KR10-2017-0120338 | 2017-09-19 | ||
KR1020180101389A KR102133218B1 (ko) | 2017-09-19 | 2018-08-28 | 체지방 감소 보조제 및 베타글루칸을 유효성분으로 하는 비만 예방 또는 치료용 조성물 |
KR10-2018-0101389 | 2018-08-28 | ||
PCT/KR2018/009976 WO2019059550A2 (ko) | 2017-09-19 | 2018-08-29 | 체지방 감소 보조제 및 베타글루칸을 유효성분으로 하는 비만 예방 또는 치료용 조성물 |
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JP2006191830A (ja) * | 2005-01-12 | 2006-07-27 | Unitika Ltd | 脂肪の蓄積を抑制する食品 |
KR20080064703A (ko) * | 2007-01-04 | 2008-07-09 | 주식회사 글루칸 | β-글루칸 및 길경 추출물을 유효성분으로 포함하는 항비만조성물 |
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KR20080110730A (ko) * | 2006-01-06 | 2008-12-19 | 사뽀로비루가부시끼가이샤 | 대사증후군 치료제 및 이를 포함하는 식품 |
JP2007332336A (ja) * | 2006-06-13 | 2007-12-27 | Rikomu:Kk | メタボリックシンドローム治療剤 |
KR100856241B1 (ko) * | 2007-04-25 | 2008-09-03 | 웅진식품주식회사 | 한천을 이용한 다이어트 식품 조성물 |
KR101130740B1 (ko) * | 2008-04-11 | 2012-03-28 | 주식회사 한국인삼공사 | 비만 억제 또는 치료용 조성물 |
JP6380968B2 (ja) * | 2013-10-22 | 2018-08-29 | 株式会社アウレオ | 脂肪蓄積抑制剤 |
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- 2018-08-28 KR KR1020180101389A patent/KR102133218B1/ko active IP Right Grant
- 2018-08-29 CN CN201880060863.4A patent/CN111107844A/zh not_active Withdrawn
- 2018-08-29 US US16/609,734 patent/US20200206291A1/en not_active Abandoned
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JP2006191830A (ja) * | 2005-01-12 | 2006-07-27 | Unitika Ltd | 脂肪の蓄積を抑制する食品 |
KR20080064703A (ko) * | 2007-01-04 | 2008-07-09 | 주식회사 글루칸 | β-글루칸 및 길경 추출물을 유효성분으로 포함하는 항비만조성물 |
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JP2020533394A (ja) | 2020-11-19 |
US20200206291A1 (en) | 2020-07-02 |
KR20190032182A (ko) | 2019-03-27 |
KR102133218B1 (ko) | 2020-07-13 |
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