CN116173103B - 丹参在提高含防己药物安全性中的应用 - Google Patents
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Abstract
本发明属于中药领域,具体涉及丹参在降低含防己药物毒性中的应用,所述含防己药物为防己单味药或含有防己原料的中药复方制剂,所述防己和丹参的质量比为1:0.2‑8。本发明发现在含防己组方中加入丹参,可以极大程度地降低防己中防己诺林碱和粉防己碱的转移率,提高防己的用药安全性,对防己具有较大的减毒作用。
Description
技术领域
本发明属于中药领域,具体涉及丹参在提高含防己药物安全性中的应用。
背景技术
《中国药典》中规定防己的来源为防己科植物粉防己,过去将马兜铃科植物广防己也作为防己使用,但马兜铃科植物有较为明确的肾毒性,出于临床用药安全考虑,广防己的药用标准已被取消。目前允许使用的防己均为粉防己。
近年来,随着对粉防己的研究不断深入,已有研究发现和文献报道,粉防己也存在明显的肝肾毒性,即使是药典剂量给药,长时间也会造成一定的肝肾功能改变。粉防己的肝肾毒性主要与其生物碱成分有关,其中含量最高的是防己诺林碱和粉防己碱,这两个成分有镇痛、抗炎的药效,但也存在一定的毒性。
中药复方制剂的制备,一般采用传统水提取合煎的工艺,中药合煎可能会产生增效减毒的作用,一般与某味药物单煎相比,合煎后某些有效成分含量会明显增加,或某些有毒副作用成分的含量明显减少。虽然目前行业内有较多专家认可中药合煎的方式,但研究比较少,且无共性,并不是所有组方合煎后都会有增效减毒的作用。
对于粉防己的用药安全性一直是我们比较重视的研究,特别是其中的防己诺林碱和粉防己碱成分。我们在研究中发现,防己单独水煎后防己诺林碱和粉防己碱的转移率均在25%-30%之间变化。
发明内容
针对现有技术存在的不足,本发明提供一种提高含防己药物安全性的配伍组合物。可以极大程度地降低防己中防己诺林碱和粉防己碱的转移率,提高防己的用药安全性。
为了实现本发明目的,采用的技术方案如下:
本发明提供丹参在提高含防己药物安全性中的应用。
优选地,所述含防己药物为防己单味药或含有防己原料的中药复方制剂。
优选地,所述防己和丹参的质量比为1:0.2-8。
优选地,所述防己和丹参的质量比为1:1-5。
优选地,所述丹参在降低含防己药物中防己诺林碱和/或粉防己碱的含量或转移率中的应用。
优选地,所述配伍组合物包括含防己药物和丹参,其中,防己和丹参的质量比为1:0.2-8。
优选地,防己和丹参的质量比为1:1-5。
优选地,所述配伍组合物还包括药用辅料,所述药用辅料选自糊精、淀粉、硫酸钙、碳酸氢钙、交联聚维酮、交联羧甲基纤维素钠、二氧化硅、硬脂酸镁和滑石粉中的一种或几种。
本发明再一目的是提供上述配伍组合物的制备方法,包括将丹参与含防己药物混合,加水提取、浓缩即得。
优选地,所述水的质量:丹参与含防己药物总质量为6-12:1,所述提取的温度为90-100℃,所述提取的时间为1-2h,所述提取的次数为1-3。
与现有技术相比,本发明的有益效果:
(1)防己单独水煎或与其它药味组方合煎后防己诺林碱和粉防己碱的转移率均在25%-30%之间,而加入丹参合煎后防己诺林碱和粉防己碱的转移率均降至5%左右,降低了约5倍,其效果非常显著。
(2)本发明通过斑马鱼毒性试验发现,防己和丹参加水合煎后其MNLC(最大非致死浓度)和LC10(10%致死浓度)相比防己单独水煎有大幅度提高,含防己的中药组方(防己黄芪汤处方:防己、黄芪、白术、甘草)加入丹参后其MNLC(最大非致死浓度)和LC10(10%致死浓度)相比防己黄芪汤处方亦有大幅度提高,表明加入丹参后可以极大地提高防己的用药安全性。
附图说明
图1为防己诺林碱、粉防己碱混合对照品溶液的色谱图,峰a为防己诺林碱,峰b为粉防己碱。
图2为实施例1-5中防己与丹参不同质量比合煎所得干膏中防己诺林碱、粉防己碱的含量测定叠加色谱图,峰a为防己诺林碱,峰b为粉防己碱。自下而上色谱图依次为实施例1、实施例2、实施例3、实施例4、实施例5。
图3为实施例7防己黄芪汤处方加丹参合煎所得干膏中防己诺林碱、粉防己碱的含量测定色谱图,峰a为防己诺林碱,峰b为粉防己碱。
图4为对比例1防己单煎所得干膏中防己诺林碱、粉防己碱的含量测定色谱图,峰a为防己诺林碱,峰b为粉防己碱。
图5为对比例2防己黄芪汤处方干膏中防己诺林碱、粉防己碱的含量测定色谱图,峰a为防己诺林碱,峰b为粉防己碱。
注:横纵坐标不清晰不影响本发明技术方案的公开和理解。
具体实施方式
下面结合具体实施方式对本发明做进一步说明。
实施例1-6配伍组合物原料用量如表1所示。
表1配方表
实施例 | 防己(重量份) | 丹参(重量份) |
实施例1 | 1 | 0.2 |
实施例2 | 1 | 0.5 |
实施例3 | 1 | 1 |
实施例4 | 1 | 2 |
实施例5 | 1 | 5 |
实施例6 | 1 | 8 |
实施例1-6防己与丹参配伍组合物的制备方法如下:
取防己饮片和丹参饮片,加水煎煮2次,第一次加8倍量的水煎煮1.5小时,第二次加6倍量的水煎煮1小时,水煎液过滤,于60℃减压浓缩至干,再于60℃减压真空干燥成干膏。测定干膏中防己诺林碱和粉防己碱含量并计算转移率,结果见下表2。
实施例7
取防己饮片2份、黄芪饮片2.5份、白术饮片1.5份、甘草饮片1份,即防己黄芪汤处方(出自《金匮要略》),加丹参饮片4份,加水煎煮3次,第一次加8倍量的水煎煮1小时,第二次加6倍量的水煎煮1小时,第三次加6倍量的水煎煮1小时,水煎液过滤,于60℃减压浓缩至干,再喷雾干燥成干膏。
对比例1
取防己饮片,加水煎煮2次,第一次加8倍量的水煎煮1.5小时,第二次加6倍量的水煎煮1小时,水煎液过滤,于60℃减压浓缩至干,再于60℃减压真空干燥成干膏。
对比例2
取防己饮片2份、黄芪饮片2.5份、白术饮片1.5份、甘草饮片1份,即防己黄芪汤处方(出自《金匮要略》),加水煎煮2次,第一次加8倍量的水煎煮1.5小时,第二次加6倍量的水煎煮1小时,水煎液过滤,于60℃减压浓缩至干,再于60℃减压真空干燥成干膏。
试验1
用HPLC法测定实施例1-7与对比例1-2干膏粉中防己诺林碱和粉防己碱的含量。
高效液相色谱法测定防己诺林碱和粉防己碱的含量方法如下:
高效液相色谱条件:
仪器名称:安捷伦1260高效液相色谱仪
色谱柱:ZORBAX Eclipse Plus C18(柱长150mm,内径4.6mm,粒径5μm)
流速:1.0ml/min
柱温:25℃
检测波长:237nm
流动相:以乙腈-甲醇-水-冰醋酸(40:30:30:1)(每100ml含十二烷基磺酸钠0.41g)
对照品溶液的制备:精密称取防己诺林碱对照品(中国食品药品检定研究院,110793-201807,含量以98.3%计)和粉防己碱对照品(中国食品药品检定研究院,批号:110711-201810,含量以99.6%计)适量,加甲醇溶液制备成每1ml含防己诺林碱51.07μg、含粉防己碱103.70μg的混合对照品溶液。
供试品溶液的制备:取防己单煎、防己与夏枯草等药味合煎所得浸膏干燥后的干膏适量,加入50%乙醇25ml,称定重量,超声处理(功率200W,频率40kHz)30分钟,取出,放冷,再称定重量,用50%乙醇补足减失的重量,离心(8000转/分钟)10分钟,取上清液,即得。
防己诺林碱、粉防己碱混合对照品溶液的色谱图见图1;实施例1-5防己与丹参不同质量比合煎所得干膏中防己诺林碱、粉防己碱的含量测定叠加色谱图见图2;实施例7防己黄芪汤处方加丹参合煎所得干膏中防己诺林碱、粉防己碱的含量测定色谱图见图3;对比例1防己单煎所得干膏中防己诺林碱、粉防己碱的含量测定色谱图见图4;对比例2防己黄芪汤处方合煎所得干膏中防己诺林碱、粉防己碱的含量测定色谱图见图5。并计算转移率,结果见下表2
通过上述色谱条件,测定各实施例和对比例中防己诺林碱和粉防己碱的含量,并计算转移率,结果见下表2。
表2
试验2
取实施例3-5、实施例7和对比例1-2制备的干膏进行斑马鱼毒性试验,计算各样品对斑马鱼的MNLC(最大非致死浓度)和LC10(10%致死浓度)。
试验方法:
随机选取2dbf野生型AB品系斑马鱼于6孔板中,每孔(实验组)均处理30尾斑马鱼,同时设置正常对照组,每孔容量为3mL。28℃处理72h,每天统计各实验组的斑马鱼死亡数量并及时移除,72h后统计各实验组急性毒性发生率。用Origin 8.0统计学软件绘制最佳的“浓度-死亡率”效应曲线,并计算样品对斑马鱼的MNLC和LC10。
MNLC(最大非致死浓度)和LC10(10%致死浓度)结果见表3,浓度-死亡率结果见表4。
表3 MNLC(最大非致死浓度)和LC10(10%致死浓度)结果
组别 | MNLC(μg/mL) | LC10(μg/mL) |
实施例3 | 3379 | 3500 |
实施例4 | 3427 | 3474 |
实施例5 | 2938 | 2982 |
实施例7 | 2923 | 2967 |
对比例1 | 359 | 367 |
对比例2 | 1945 | 1989 |
表4浓度-死亡率结果
上述详细说明是针对本发明其中之一可行实施例的具体说明,该实施例并非用以限制本发明的专利范围,凡未脱离本发明所为的等效实施或变更,均应包含于本发明技术方案的范围内。
Claims (2)
1.丹参在降低防己药物中防己诺林碱和/或粉防己碱的含量或转移率中的应用,其特征在于,所述防己药物为防己单味药或中药复方制剂,所述防己和丹参的质量比为1:0.2-8,所述中药复方制剂由防己饮片2份、黄芪饮片2.5份、白术饮片1.5份、甘草饮片1份和丹参饮片4份制成,所述丹参降低防己药物中防己诺林碱和/或粉防己碱的含量或水提取转移率的具体方法为将按重量配比的丹参与防己药物混合,加水提取、浓缩。
2.根据权利要求1所述的应用,其特征在于,所述防己和丹参的质量比为1:1-5。
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