CN104435447B - 一种葛山降脂缓释制剂及其制备方法 - Google Patents
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Abstract
本发明涉及一种中药制剂，具体涉及葛山降脂制剂及其制备方法，属于中药领域。其由中药提取物和辅料组成；所述中药提取物由重量百分比为：32％的葛根，32％的山楂，15％的泽泻，13％的何首乌和8％的当归制成，所述中药提取物与辅料的重量比为1:2～5。所述辅料由15％～30％的骨架材料、10％～50％的填充剂、10％～30％的兼矫味的致孔剂和1％～2％的润滑剂组成。所述骨架材料优选为黄原胶和海藻酸钠的混合物，所述混合物中黄原胶：海藻酸钠的重量比为3：1。所述填充剂优选为预胶化淀粉；所述致孔剂优选甘露醇；所述润滑剂优选为硬脂酸镁。
Description
技术领域
本发明涉及一种中药制剂，具体涉及葛山降脂缓释制剂及其制备方法，属于中药领域。
背景技术
高脂血症临床上分为原发和继发两大类，系许多疾病中脂质和脂蛋白代谢紊乱的结果。特别是高脂血症引发动脉粥样硬化，导致心脑血管意外，病情凶险，预后不良。目前，临床上常用的降脂化学药，均存在较大的副作用，且长期使用，部分药物可因胃肠反应大，引发脂溶性维生素吸收不良等后果。此外，由于人群的个体差异较大，对药物的疗效和反应也存在较大差别。所以，随着中西医结合的不断发展及对中药研究的不断深入，根据传统中医学理论，结合当代中药研究成果，辩证与辨病相结合，选择适宜的中药配伍应用，利于长期服用，副反应小，同时可调节人体机体功能的平衡的新型天然中药复方制剂，对治疗高脂血症，预防心脑血管疾病及老年性病变有着重要意义。
缓释制剂(sustainedreleasepreparation)是指通过适当的方法，延缓药物在体内的释放、吸收、分布、代谢和排泄等过程，从而达到延长药物作用、减少毒副作用等目的的一类制剂。其可避免普通制剂频繁给药所出现的“峰谷”现象，使药物的安全性、有效性和适应性有所提高。目前由于中药提取物的成分复杂性，中药缓释制剂在制备上存在着辅料筛选困难，成形工艺差和药物释放速度不稳定等技术问题。葛山降脂颗粒源于安徽省名中医高道凡先生的多年临床经验方。处方由葛根、炒山楂、泽泻、制何首乌和当归五味药组成。临床上主要应用于各种诱因导致的高脂血症，具有起效快，疗效高，副作用小等特点。但目前已上市制剂仅有葛山降脂颗粒一种，服药次数多，患者体内血药浓度不稳定，不能有效地发挥其药理作用，远不能满足临床需要。
发明内容
针对目前存在的技术问题，本发明提供一种葛山降脂缓释制剂及其制备方法，降低患者用药频率为一日一次，使药物的释放更加稳定，提高药效。
本发明的一个目的是提供一种葛山降脂缓释制剂，其由中药提取物和辅料组成；所述中药提取物由重量百分比为：32％的葛根，32％的山楂，15％的泽泻，13％的何首乌和8％的当归制成，所述中药提取物与辅料的重量比为1:2～5。
在本发明的一个实施方案中，所述辅料由15％～30％的骨架材料、10％～50％的填充剂、10％～30％的兼矫味的致孔剂和1％～2％的润滑剂组成。
在本发明的另一个实施方案中，所述骨架材料为羟丙甲纤维素、黄原胶、卡波姆和海藻酸钠之一或它们的混合物。所述填充剂为微晶纤维素、乳糖、磷酸氢钙、预胶化淀粉或它们的混合物。所述致孔剂为甘露醇、山梨醇、聚乙二醇或葡萄糖。所述润滑剂为滑石粉、微粉硅胶或硬脂酸镁。
在本发明更进一步地实施方案中，所述骨架材料优选为黄原胶和海藻酸钠的混合物，所述混合物中黄原胶：海藻酸钠的重量比为3：1。所述填充剂优选为预胶化淀粉；所述致孔剂优选甘露醇；所述润滑剂优选为硬脂酸镁。
本发明的另一个目的是提供一种制备所述葛山降脂颗粒的方法，具体步骤如下：
(1)将相应重量份的泽泻药材干燥分别粉碎成细粉；
(2)将相应重量份的葛根、山楂、何首乌和当归加8倍量水煎煮三次，每次为1.5小时，滤过，合并滤液，浓缩至60℃时相对密度为1.10～1.20的浸膏；加乙醇至含醇量达70％，搅匀，静置，取上清液回收乙醇，干燥粉碎得细粉，
(3)将步骤(1)获得的细粉、步骤(2)获得的细粉混合均匀，再加入相应重量份的骨架材料、填充剂和致孔剂混匀，用无水乙醇作润湿剂制成软材，制粒，干燥，整粒加入润滑剂混匀，压片，即得。
在进一步地实施方案中，步骤(1)中所述泽泻粉碎的粒度为100～200目的细粉，更优选的是所述泽泻粉碎的细度为150目的细粉。步骤(2)中所述细粉的粒度为150目。
本发明针对裸花紫珠提取物的相关特点，选择合适的相关辅料，从而获得了一种成型工艺好、稳定性佳及药物释放速度稳定的葛山降脂缓释制剂。
具体实施方式
下面将进一步的举例说明本发明。需要指出的是，以下说明仅仅是对本发明要求保护的技术方案的举例说明，并非对这些技术方案的任何限制。本发明的保护范围以所附权利要求书记载的内容为准。
实施例1
步骤1：将泽泻15kg干燥粉碎成细粉，过150目筛备用；
步骤2：将相应重量份的32kg的葛根，32kg的山楂，13kg的何首乌和8kg的当归加8倍量水煎煮三次，每次1.5小时，滤过，合并滤液，浓缩至60℃时相对密度为1.10～1.20的浸膏；加乙醇至含醇量达70％，搅匀，静置，取上清液回收乙醇，干燥粉碎得细粉，
步骤3：将步骤(1)获得的细粉、步骤(2)获得的细粉混合均匀，再加入相应重量份的黄原胶、海藻酸钠、预胶化淀粉和甘露醇混匀，用70％乙醇作润湿剂制成软材，制粒，干燥，整粒加入硬脂酸镁混匀，压片，片重500mg，即得。所述辅料与中药提取物的重量比为3:1，黄原胶、海藻酸钠、预胶化淀粉、甘露醇和硬脂酸镁的重量百分比分别为30％：10％：40％：19％:1％。
实施例2-5
除下表内容外，其他制备工艺同实施例1，具体见下表：
实施例6缓释片体外释放度试验
释放介质为模仿人体胃肠道环境(2h前为0.1mol/L盐酸，2h后为pH6.8的PBS缓冲液)，分别考察各实施例制备的缓释片剂的释放度。
释放度考察方法：首先通过HPLC测定缓释片中葛根素、枸橼酸和23-乙酰泽泻醇B的含量，再将同批号缓释片放入释放介质中考察释放度。
对比例1为山东绿因药业有限公司生产的葛山降脂颗粒。
实施例7缓释片在大鼠体内释放度研究
取SD大鼠，禁食12h后，灌胃给药(以中药提取物计100mg/kg)，分别在1、4、8、12和24h眼球取血，采用HPLC-MS测定各时间点血药浓度，具体结果如下：
本发明内容仅仅举例说明了要求保护的一些具体实施方案，其中一个或更多个技术方案中所记载的技术特征可以与任意的一个或多个技术方案相组合，这些经组合而得到的技术方案也在本申请保护范围内，就像这些经组合而得到的技术方案已经在本发明公开内容中具体记载一样。
Claims (2)
1.一种葛山降脂缓释制剂，其特征在于，其由中药提取物和辅料组成；所述中药提取物由重量百分比为：32%的葛根，32%的山楂，15%的泽泻，13%的何首乌和8%的当归制成，所述中药提取物与辅料的重量比为1:2～5；
所述辅料由15%～30%的骨架材料、10%～50%的填充剂、10%～30%的兼矫味的致孔剂和1%～2%的润滑剂组成；
所述骨架材料为黄原胶和海藻酸钠的混合物，所述混合物中黄原胶：海藻酸钠的重量比为3：1；
所述填充剂为预胶化淀粉；所述致孔剂甘露醇；所述润滑剂为硬脂酸镁。
2.一种制备权利要求1所述的缓释制剂的方法，其特征在于，具体步骤如下：
（1）将相应重量份的泽泻药材干燥分别粉碎成细粉；
（2）将相应重量份的葛根、山楂、何首乌和当归加8倍量水煎煮三次，每次为1.5小时，滤过，合并滤液，浓缩至60℃时相对密度为1.10～1.20的浸膏；加乙醇至含醇量达70%，搅匀，静置，取上清液回收乙醇，干燥粉碎得细粉，
（3）将步骤（1）获得的细粉、步骤（2）获得的细粉混合均匀，再加入相应重量份的骨架材料、填充剂和致孔剂混匀，用无水乙醇作润湿剂制成软材，制粒，干燥，整粒加入润滑剂混匀，压片，即得。
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