CN109316498A - 一种低毒银杏酮酯组合物的制备方法 - Google Patents
一种低毒银杏酮酯组合物的制备方法 Download PDFInfo
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Abstract
本发明涉及一种低毒银杏酮酯组合物的制备方法，包括如下步骤：取银杏叶粉碎，用65‑75％的乙醇加热回流提取多次，滤过，滤液备用；药渣加纯水加热回流0.5‑1小时，滤过，滤液与上述滤液合并，浓缩成稠膏，用70‑90℃的纯水溶解，静置冷却，滤过，滤液上大孔树脂柱；依次用20％乙醇、30％乙醇及50％乙醇洗脱，20％乙醇、30％乙醇洗脱液浓缩至无醇味，上聚酰胺柱，用乙醇洗脱；50％乙醇洗脱液与乙醇洗脱液合并，浓缩至无醇味，浓缩液用环己烷萃取，弃去环己烷萃取液，浓缩液喷雾干燥，粉碎，即得低毒银杏酮酯组合物。根据本发明制备的低毒银杏酮酯组合物，毒性成分含量进一步降低，溶剂残留物含量低，有效组分含量稳定，大大提高给药安全性。
Description
技术领域
本发明属于中药技术领域，主要涉及一种低毒银杏酮酯组合物的制备方法。
背景技术
银杏叶是一种疗效确切、用途广泛的药物，它的提取物主要有效成分为黄酮(Flavonoids)和萜内酯，前者以槲皮素、山柰酚及异鼠李素及其糖苷为主，后者以银杏内酯(Ginkgolides)及白果内酯(Bilobalide)为主。临床验证银杏叶提取物对心、脑血管及外周血管循环障碍性疾病的疗效颇为满意。当前主要用于治疗缺血性脑血管疾病及其引起的眩晕、听力障碍、老年性痴呆、糖尿病神经病变、肺心病以及癫痫的辅助治疗，如银杏酮酯原料药及其制剂等。
但是，银杏叶提取物同时含有毒性组分银杏酸，其含量范围有待进一步降低，以尽可能减少患者用药伤害，并且，目前适用标准中银杏叶提取物有效成分的含量范围过于宽泛，不利于准确用药，因此，有必要对银杏酮酯进行深入研究，以解决现有产品存在的问题。
发明内容
鉴于以上问题，本发明的目的是提供一种毒性含量少、有效成分含量更精确的银杏酮酯组合物的制备方法，以增强用药安全、提高用药效果。本发明的具体技术方案如下：
一种低毒银杏酮酯组合物的制备方法，包括如下步骤：
取银杏叶粉碎，用65-75％的乙醇加热回流提取多次，滤过，滤液备用；
药渣加纯水加热回流0.5-1小时，滤过，滤液与上述滤液合并，浓缩成稠膏，用70-90℃的纯水溶解，静置冷却，滤过，滤液上大孔树脂柱；
依次用20％乙醇、30％乙醇及50％乙醇洗脱，20％乙醇、30％乙醇洗脱液浓缩至无醇味，上聚酰胺柱，用乙醇洗脱；50％乙醇洗脱液与乙醇洗脱液合并，浓缩至无醇味，浓缩液用环己烷萃取，弃去环己烷萃取液，浓缩液喷雾干燥，粉碎，即得银杏酮酯。
根据上述制备方法得到的低毒银杏酮酯组合物，以重量百分比计，包括如下组分：总黄酮，44-55％；白果内酯(C15H18O8)，大于2.6％；芦丁，小于4％；槲皮素，小于等于0.4％；总银杏酸，小于等于4ppm；水分，小于5％；环己烷残留物，小于等于0.002％。
进一步地，以重量百分比计，所述低毒银杏酮酯组合物还包括如下组分：总黄酮醇苷24-35％；萜类内酯以白果内酯(C15H18O8)、银杏内酯A(C20H24O9)、银杏内酯B(C20H24O10)和银杏内酯C(C20H24O11)的总量计，为6-12％。
本发明的技术方案具有如下优点：
本发明提供的低毒银杏酮酯组合物的制备方法，过程可控、产品质量高，毒性成分含量进一步降低，溶剂残留物含量低，有效组分含量范围更精确和稳定，大大降低给药伤害并提高给药安全性。
具体实施方式
下面，对本发明的实施例进行详细说明，但所述内容不能被认为用于限定本发明的实施范围。凡依本发明申请范围所作的均等变化与改进等，均应归属于本发明的保护涵盖范围之内。另外，需要说明的是，在不冲突的情况下，本发明创造中的实施例及实施例中的特征可以相互组合。
实施例1
本实施例涉及一种低毒银杏酮酯组合物的制备方法，步骤为：取银杏叶粉碎，用65-75％的乙醇加热回流提取多次，滤过，滤液备用，药渣加纯水加热回流0.5-1小时，滤过，滤液与上述滤液合并，浓缩成稠膏，用70-90℃的纯水溶解，静置冷却，滤过，滤液上大孔树脂柱，依次用20％乙醇、30％乙醇及50％乙醇洗脱，20％乙醇、30％乙醇洗脱液浓缩至无醇味，上聚酰胺柱，用乙醇洗脱；50％乙醇洗脱液与乙醇洗脱液合并，浓缩至无醇味，浓缩液用环己烷萃取，弃去环己烷萃取液，浓缩液喷雾干燥，粉碎，即得低毒银杏酮酯组合物。
制备过程中使用纯水，可保证银杏酸保持在小于现有标准的较低含量，并且，可降低槲皮素和芦丁的含量。
实施例2
根据实施例1的制备方法制得的低毒银杏酮酯组合物，以重量百分比计，包括如下组分：总黄酮，44-55％；白果内酯(C15H18O8)，大于2.6％；芦丁，小于4％；槲皮素，小于等于0.4％；总银杏酸，小于等于4ppm；水分，小于5％；环己烷残留物，小于等于0.002％。
可选地，所述低毒银杏酮酯组合物还包括如下组分：总黄酮醇苷24-35％；萜类内酯以白果内酯(C15H18O8)、银杏内酯A(C20H24O9)、银杏内酯B(C20H24O10)和银杏内酯C(C20H24O11)的总量计，为6-12％。
现有标准中，银杏酸是用薄层扫描法测定，灵敏度较低；本发明的技术方案中银杏酸通过液质联用法测定，灵敏度高，测量更为精确。上述其他各组分含量按照2015版中国药典标准测定，2015版中国药典未公布的，按照行业标准或本领域技术人员常用的方法测定。
Claims (3)
1.一种低毒银杏酮酯组合物的制备方法，其特征在于，包括如下步骤：
取银杏叶粉碎，用65-75％的乙醇加热回流提取多次，滤过，滤液备用；
药渣加纯水加热回流0.5-1小时，滤过，滤液与上述滤液合并，浓缩成稠膏，用70-90℃的纯水溶解，静置冷却，滤过，滤液上大孔树脂柱；
依次用20％乙醇、30％乙醇及50％乙醇洗脱，20％乙醇、30％乙醇洗脱液浓缩至无醇味，上聚酰胺柱，用乙醇洗脱；50％乙醇洗脱液与乙醇洗脱液合并，浓缩至无醇味，浓缩液用环己烷萃取，弃去环己烷萃取液，浓缩液喷雾干燥，粉碎，即得所述低毒银杏酮酯组合物。
2.权利要求1的制备方法得到的低毒银杏酮酯组合物，其特征在于，以重量百分比计，所述低毒银杏酮酯组合物包括如下组分：总黄酮，44-55％；白果内酯，大于2.6％；芦丁，小于4％；槲皮素，小于等于0.4％；总银杏酸，小于等于4ppm；水分，小于5％；环己烷残留物，小于等于0.002％。
3.根据权利要求2所述的低毒银杏酮酯组合物，其特征在于，以重量百分比计，还包括如下组分：总黄酮醇苷24-35％；萜类内酯以白果内酯、银杏内酯A、银杏内酯B和银杏内酯C的总量计，为6-12％。
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