CN117100758B - 拟人参皂苷Rh2制备治疗肥胖和/或肥胖并发症的药物的用途 - Google Patents
拟人参皂苷Rh2制备治疗肥胖和/或肥胖并发症的药物的用途 Download PDFInfo
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Abstract
本发明涉及医药技术领域，具体涉及拟人参皂苷Rh2制备治疗肥胖和/或肥胖并发症的药物的用途，药物能够降低体重、降低甘油三酯浓度、减轻胰岛素抵抗或/和提高葡萄糖耐量。本发明通过大量的创造性实验发现，拟人参皂苷Rh2具有减重、降低甘油三酯浓度、改善胰岛素抵抗及提高葡萄糖耐量的作用，证明了化合物拟人参皂苷Rh2可有效地防治高脂饮食引起的肥胖，并减轻因肥胖造成的胰岛素抵抗，为目前普遍存在的高脂或者高热量饮食引起的肥胖以及各种并发症的治疗提供了一个新的选择思路。
Description
技术领域
本发明涉及医药技术领域，具体涉及拟人参皂苷Rh2制备治疗肥胖和/或肥胖并发症的药物的用途。
背景技术
肥胖是现代社会非常常见的代谢性疾病。肥胖成因复杂，通常情况下肥胖是由遗传因素、环境、个人饮食和运动行为共同导致的。当人体进食热量超过消耗热量时，多余热量会以脂肪形式储存于体内，当储存量超过机体正常生理需要量，到达一定值时即成为肥胖。通常，肥胖者的预期寿命较短；他们比正常体重的人更早、更频繁、更严重地遭受多种疾病的困扰。例如肥胖患者更易受到糖尿病的影响，在全球范围内，大约90%的Ⅱ型糖尿病病例是由体重过重引起的。肥胖也是癌症的重要原因，截至2018年，全球每25个确诊癌症患者中，就有一人的病因是超重和肥胖。在美国，与肥胖相关的癌症的发病率在25至49岁的相对年轻的成年人中呈上升趋势。肥胖与心血管事件的关联表现在糖尿病和高血压等疾病中，且肥胖者随着年龄的增长有认知能力加速下降的风险。对长期肥胖者的大脑体积的研究表明，体内脂肪增加与大脑组织的萎缩有关，尤其是在大脑的颞叶和额叶。BMI大于或等于25与大脑尺寸的减小有关，并增加了阿尔茨海默病的风险。肥胖患者体内过多的脂肪会影响性激素水平导致不孕不育风险大大提高。
目前减肥主要手段是生活方式干预和医疗手段，前者包括饮食控制和增强运动，后者则包括肠道菌群干预、手术干预和药物使用。目前国内外有六种被批准的减肥药物，其中盐酸洛卡斯林，芬特明/托吡酯，罗卡西林和纳曲酮四种药物作用于中枢神经系统，通过降低食欲达到减少饮食摄入的作用；利拉鲁肽作为GLP-1受体激动剂，能促进胰岛素分泌并增加饱腹感；奥利司他是胃脂肪酶和胰脂肪酶抑制剂，可以直接抑制脂肪的吸收从而达到减少热量摄入的目的。但是由于各种禁忌症的存在，患者难以接受的不良反应或给药途径限制（GLP-1受体激动剂需要注射给药），减肥药物的实际应用受到很大限制。因此进一步研究开发疗效出色、减肥作用持久、不良反应少的减肥药物对于肥胖的治疗具有重要意义。
近年来，随着人们生活方式的改变，用于减肥的中药单方以及复方不断出现，一些中药已经被证明能够减轻体重、降低血脂，并抑制肝脏脂肪蓄积。这为广大肥胖患者提供了新的治疗选择。但中药是天然植物的混合物，组成成分非常复杂，具体发挥作用的成分不明确，这就导致了其不良反应未知、质控标准缺乏、药物作用机制不明、药代动力学参数无法获得等诸多问题，对其基础研究、临床应用、规模化工业生产和国际认可造成了很大的障碍。
发明内容
针对中药组成成分非常复杂，具体发挥作用的成分不明确的技术问题，本发明提供一种拟人参皂苷Rh2制备治疗肥胖和/或肥胖并发症的药物的用途。
本发明技术方案如下：
一种拟人参皂苷Rh2制备治疗肥胖和/或肥胖并发症的药物的用途，药物能够降低体重、降低甘油三酯浓度、减轻胰岛素抵抗或/和提高葡萄糖耐量。
进一步的，肥胖并发症为糖尿病。
进一步的，拟人参皂苷Rh2的纯度大于98%。
进一步的，药物中拟人参皂苷Rh2含量为98%。
进一步的，药物剂型为注射剂。
进一步的，注射剂的制备方法为先将拟人参皂苷Rh2溶于溶剂DMSO中，再将此溶液加入溶媒中漩涡震荡混匀，溶媒为体积比5：1的DMSO和玉米油的混合液体。
本发明的有益效果在于：
本发明通过大量的创造性实验发现，拟人参皂苷Rh2具有减重、降低甘油三酯浓度、改善胰岛素抵抗及提高葡萄糖耐量的作用，证明了化合物拟人参皂苷Rh2可有效地防治高脂饮食引起的肥胖，并减轻因肥胖造成的胰岛素抵抗，为目前普遍存在的高脂或者高热量饮食引起的肥胖以及各种并发症的治疗提供了一个新的选择思路。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，对于本领域普通技术人员而言，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1是拟人参皂苷Rh2对小鼠体重的影响图。
图2是拟人参皂苷Rh2对小鼠甘油三酯浓度的影响图。
图3是拟人参皂苷Rh2对小鼠血清胰岛素浓度的影响图。
图4是拟人参皂苷Rh2对小鼠口服葡萄糖耐量的影响图。
具体实施方式
为了使本技术领域的人员更好地理解本发明中的技术方案，下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都应当属于本发明保护的范围。
本发明具体实施方式使用的拟人参皂苷Rh2购自成都曼思特生物科技有限公司，纯度为98%。
实施例1 肥胖小鼠模型建立及药物干预
选用7-8周龄的C57BL/6小鼠，小鼠购于维通利华公司，饲养于山东省立医院实验动物中心（SPF级），饲养条件为相对湿度50%-60%、室温20±2℃、昼夜时间12h/12h，自由饮水及进食。适应性喂养1周后，给予小鼠高脂饲料喂养。
喂养13周后，将小鼠分为单纯高脂组（HFD 0）、高脂+拟人参皂苷Rh2低剂量组（HFD30）、高脂+拟人参皂苷Rh2高剂量组（HFD 60），每组小鼠数量均为5只。
药物配置方法如下：
先将拟人参皂苷Rh2溶于溶剂DMSO中，再将此溶液加入溶媒中漩涡震荡混匀，溶媒为体积比5：1的DMSO和玉米油的混合液体，得到拟人参皂苷Rh2注射剂。
给药方式如下：
腹腔注射，频率为每日一次，高脂+拟人参皂苷Rh2低剂量组给药浓度（拟人参皂苷浓度）为30mg/kg/d，高脂+拟人参皂苷Rh2高剂量组给药浓度（拟人参皂苷浓度）为60mg/kg/d，给药持续时间为4周。
同时，向单纯高脂组腹腔注射溶媒，频率为每日一次。
对实施例1各处理组小鼠进行下列分析检测：
1、体重监测
每周记录体重一次，直到药物干预时间结束，共记录17次。
拟人参皂苷Rh2对小鼠体重的影响如图1所示，给药四周后，与单纯高脂组相比，高脂+拟人参皂苷Rh2高剂量组小鼠体重明显降低（*p<0.05）。
2、降低甘油三酯效果验证
药物干预4周后，使用普利莱甘油三酯测定试剂盒检测小鼠血清中甘油三酯浓度。
拟人参皂苷Rh2对小鼠甘油三酯浓度的影响如图2所示，高脂+拟人参皂苷Rh2低剂量组、高脂+拟人参皂苷Rh2高剂量组与单纯高脂组相比，甘油三酯含量有降低趋势。
3、减轻胰岛素抵抗效果验证
药物干预4周后，使用小鼠胰岛素酶联免疫试剂盒检测血清胰岛素浓度。
拟人参皂苷Rh2对小鼠血清胰岛素浓度的影响如图3所示，高脂+拟人参皂苷Rh2低剂量组、高脂+拟人参皂苷Rh2高剂量组与单纯高脂组相比，血清胰岛素含量降低明显（**p<0.01）。
4、口服葡萄糖耐量试验
药物干预4周后，进行小鼠口服葡萄糖耐量试验，0、30、60、90、120min采用ACCU血糖监测仪检测小鼠血糖水平。
拟人参皂苷Rh2对小鼠口服葡萄糖耐量的影响如图4所示，高脂+拟人参皂苷Rh2低剂量组、高脂+拟人参皂苷Rh2高剂量组的葡萄糖耐量在给药后有所改善，其中90分钟时间点有统计学差异（*p<0.05）。
尽管通过参考附图并结合优选实施例的方式对本发明进行了详细描述，但本发明并不限于此。在不脱离本发明的精神和实质的前提下，本领域普通技术人员可以对本发明的实施例进行各种等效的修改或替换，而这些修改或替换都应在本发明的涵盖范围内/任何熟悉本技术领域的技术人员在本发明揭露的技术范围内，可轻易想到变化或替换，都应涵盖在本发明的保护范围之内。
Claims (4)
1.一种拟人参皂苷Rh2制备治疗肥胖的药物的用途，其特征在于，药物能够降低体重、降低甘油三酯浓度、减轻胰岛素抵抗和提高葡萄糖耐量。
2.如权利要求1所述的用途，其特征在于，拟人参皂苷Rh2的纯度大于98%。
3.如权利要求1所述的用途，其特征在于，药物剂型为注射剂。
4.如权利要求3所述的用途，其特征在于，注射剂的制备方法为先将拟人参皂苷Rh2溶于溶剂DMSO中，再将此溶液加入溶媒中漩涡震荡混匀，溶媒为体积比5：1的DMSO和玉米油的混合液体。
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