豨莶丸的配方优化及治疗实验性膝骨性关节炎的药效、机理探讨
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摘要
中药炮制是根据中医药理论,依照辨证施治用药的需要和药物自身的性质,以及调剂、制剂的不同要求,所采取的一项制药技术。是一项传统的制药技术。中药经过炮制后可以达到洁净药材,增强疗效,降低毒性,改变作用趋势等目的。古医籍中记载有不少单味中药炮制后功效发生较大改变进而出现生熟异用的情况。如生地与熟地、生首乌与制首乌、生豨莶草与制豨莶草等。炮制的起源可以追索到汉代,在长沙马王堆汉墓出土的《五十二病方》中就记载有多种单味中药的简单炮制方法。随着时间的推进,不少古老炮制方法保留到了今天,但也有不少炮制方法在演变的过程中逐渐背离了原始的内容,出现古今炮制方法和炮制目的不一致。这种从古到今的改变是合理的或是由于某些原因导致的不该有的改变呢?要弄清这些问题首先需要进行文献考证,其次要开展相关的实验加以探讨,只有这样才能得出正确的答案。
豨莶草首载于《新修本草》,为菊科一年生草本植物豨莶、腺梗豨莶、和毛梗豨莶的地上部分。临床用生豨莶草和酒蒸豨莶草两种炮制品,传统认为生豨莶草以清肝热,解毒邪为主,用于痈肿疔疮,风疹、湿疹,风湿热痹,湿热黄疸等证;酒蒸后祛风湿、强筋骨力强并具有补肝肾的作用,用于中风偏瘫,风湿痹痛,腰膝酸软无力等证。药典中还收载有用单味豨莶草制备的制剂——豨莶丸。
中国药典从 1963 年版开始收载豨莶丸,制备方法是:豨莶草 1000g,切碎,取出粗茎 500g,加水煎煮 2 次,每次 2 小时,合并煎液,滤过,滤液浓缩成稠膏。其余 500g 用黄酒 1000g 浸拌,置罐中,加盖封闭,隔水加热至酒吸尽,取出,与上述稠膏混合,干燥,粉碎成细粉,过筛,混匀。每 100g 粉末加炼蜜 170～200g 制成大蜜丸。每丸重 9g。这一制备方法一直延续到 2005 年。功能主治:祛风湿,利关节,解毒。用于风湿痹痛,筋骨无力,腰膝酸软,四肢麻痹,半身不遂,风疹湿疮。宋·《证类本草》中也收载有一个豨莶丸(即古方豨莶丸),为单一豨莶草的嫩茎叶,经用酒蒸制九次后制备成的蜜丸。主治中风,同时长服久服还可以强身健体。可见今方豨莶丸无古方豨莶丸的功效神奇。古方豨莶丸是如何演变成今方豨莶丸的无文献可查证。因此决定对今方豨莶丸进行配方优化实验,又由于临床常用豨莶丸治疗骨性关节炎病,因此优化实验完成后探讨了优化方治疗膝关节骨性关节炎的药效和作用机理。
本课题旨在探讨用文献学结合现代实验的方法解决炮制学中的相关问题的可行性,以单味中药生熟各半制成的中成药-豨莶丸为研究对象,运用文献学的方法对豨莶草和豨莶丸作多方面内容的考证,用药理实验结合化学实验的方法作豨莶草炮制前后的对比研究,以炮制前后药效和成分方面的变化作为依据,用直接实验设计法对今方豨莶丸进行配方优化的实验研究,对通过优化研究组成的新方进行主要药效学研究及作用机理的探讨。
本研究实验分为三部分。
2 豨莶丸的配方优化及对实验性膝骨性关节炎的药效及作用机理探讨
1 文献考证
1.1 目的
由于今方和古方豨莶丸在配方功效方面存有差异,因此对豨莶草原植物来源、
入药部位、炮制历史沿革及 古方豨莶丸的制备和应用进行文献学考证,找出今方和
古方豨莶丸的相关背景资料。
1.2 结果
对豨莶草考证的结果表明:
⑴古代当时至少有三种植物当成豨莶草药用, ①是名为火杴的植物,经考证应
为茄科植物龙葵;②是名为猪膏草的植物,经考证为菊科植物腺梗豨莶,为现代豨
莶草原植物之一;③是名为地菘的植物,经考证为茄科植物天明精,是有毒植物,
为现代中药鹤虱的原植物。正品豨莶草应为腺梗豨莶,天明精及龙葵均为混淆品,
不能做豨莶草用。至于从 1977 年版药典起开始收载的豨莶和毛梗豨莶则为现代扩大
药源时加入的品种,与腺梗豨莶同科同属,经化学及药理实验证明与腺梗豨莶相似 。
⑵古代豨莶草只以嫩茎叶入药,粗茎属于非入药部分要求除掉。
⑶古文献中记载豨莶草的炮制方法有清蒸、酒蜜蒸、酒蒸、酒炒、清炒。蒸法
中无论用辅料或不用辅料都要求蒸九次,并有强调不蒸够九次,疗效不好。
⑷豨莶草酒蒸制九次矫臭矫味,气味香美,转寒为温,活血祛风之性未改,而
温养之力更加,甚益元气,祛风逐湿之中,有补益肝肾之功,可以长服久服。适用
于肝肾虚而肾又犯风邪湿气患者,既可使邪风去又可使肝肾能较好地恢复功能。
⑸豨莶草生熟异用总结为:生用与制用,其药性与功效有别。生用或制用,均
可祛风湿、舒筋活络,但以炮制品之辛散温通力稍强,兼有补益肝肾的作用,用于
风湿痹证,骨节疼痛,或麻木拘挛者。治疮痈肿毒,取其清热解毒之功;治湿疹痒
疮,取其除湿止痒之功,宜生用。
对豨莶丸考证的结果表明:
(1)豨莶丸最早出处应是宋·《证类本草》卷十一引成纳方,而不是《中医学
大辞典》中记载的“出于《严氏济生方》”。
(2)古方豨莶丸为单一豨莶草的嫩茎叶,经用酒蒸制九次后制备的蜜丸。而今
方豨莶丸处方是生豨莶草粗茎与用酒蒸制后的嫩茎叶各一半。
(3)古方豨莶丸的功能主治主要是祛风除湿,通痹止痛,长精神,健体强身。
主治风湿痹病,关节疼痛,筋骨无力,腰膝酸软及中风引起的半身不遂,肢体麻木,
久服养精神,美容颜。今方豨莶丸清热祛湿,散风止痛。用于风湿热阻络所致的痹
病,症见肢体麻木、腰膝酸软
Processing drugs is a traditional pharmacy technology based on the traditional theories, the requirements of treatment, the quality nature of drugs and the different demands of dispensing. Traditional Chinese medicine (TCM) will strengthen its effect and degrade its toxicity by processing. There are many processing drugs which change their effects by processing are recorded in various ancient literatures such as rough Shengdi and processed Shengdi, rough Xijian and processed. However there are some difference between the traditional and contemporary processing methods and aims. In order to solve these problems, a lot of literature research and experiments are needed.
Xijian herb is a kind of annual herb recorded first in the XIN XIU BEN CAO. According to traditional theories rough Xijian mainly aims at clearing liver-heat and toxic material and is used to cure furuncle, rubella, eczema and so on. When Xijian is processed with alcohol, it has the effects of eliminating rheumatism, strengthening bones and muscles, and making up liver and kidney . Then it is used to cure palsy, rheumatic and so on.
Xijian pill has been recorded in the Chinese Pharmacopoeia from 1963. The pill preparative method in Pharmacopoeia differs in the traditional one. So this study aims at probing the possibility of solving the problems of processing drugs with literature research and contemporary experiments. Our work began with literature review of Xijian herb and Xijian pill. Then we compared the effects and ingredients of rough Xijian and processed Xijian. Furthermore we optimized the prescription and discussed the mechanism.
1. Literature researsh Motive
Because of the difference between traditional and contemporary effects, we reviewed the plant origin, applying part, processing history, preparation and application of Xijian in order to collect the background information of Xijian pill.
Result
Contemporary applying part and the processing method of Xijian are different from traditional ones. When it comes to the effects and prescription, there still are some differences between traditional and contemporary Xijian. At the some time, the effects of rough Xijian and processed Xijian are also different.
2 Processing HERBA SIEGESBECKIAE of drug action and chemical composition to contrast and study in circa . 2.1 Motive XIJIAN pill rough product and processed product for antiinflammatory anti-rheumatism and chemical composition to contrast and study to reveal processed product HERBA SIEGESBECKIAE chang in drug action and ingredient 2.2 Test methods and Result processed product HERBA SIEGESBECKIAE have apparently depressant effec to Acute inflammation chronic inflammation and immunity inflammation.it better thanrough product. acute toxicity test presentation of resultsrough product and processed product is innocuity ;thin layer chromatography convict rough product andprocessed product have much difference. 2.3 Conclusion HERBA SIEGESBECKIAE rough product and processed product have much difference in drug action and chemicial composition. 3 To make use of direct design of experiment method grading-up XIJIAN pill prescription. 3.1 Motive With drug action and chemical index to find best prescription and suitable dosage. 3.2 Method To use direct design of experiment method .tow factors are rough pachy stem and wine parboil tender stem.to set up seven levels.Then applying RDZ software compute.we can get a plan that need seven time experiments. We Select IL-1βand IL-6 synovial fluid for chemicial index that judge immunity inflammation and pathogenetic condition severity.the same time we shoose nonanol that is composition of HERBA SIEGESBECKIAE. Nonanol contents is pharmacodynamics foundational index to get grading-up prescription 3.3 Result The best prescription: rough pachy stem 0g ;wine parboil tender stem 30g. 4 To probe grading-up XIJIAN pill prescription treat ostarthritis of drug efficacy study and mechanism of action. 4.1 Motive With pharmacodynamics immunology histomorphology to sure the depressant effect to infl.and find t
豨莶草首载于《新修本草》,为菊科一年生草本植物豨莶、腺梗豨莶、和毛梗豨莶的地上部分。临床用生豨莶草和酒蒸豨莶草两种炮制品,传统认为生豨莶草以清肝热,解毒邪为主,用于痈肿疔疮,风疹、湿疹,风湿热痹,湿热黄疸等证;酒蒸后祛风湿、强筋骨力强并具有补肝肾的作用,用于中风偏瘫,风湿痹痛,腰膝酸软无力等证。药典中还收载有用单味豨莶草制备的制剂——豨莶丸。
中国药典从 1963 年版开始收载豨莶丸,制备方法是:豨莶草 1000g,切碎,取出粗茎 500g,加水煎煮 2 次,每次 2 小时,合并煎液,滤过,滤液浓缩成稠膏。其余 500g 用黄酒 1000g 浸拌,置罐中,加盖封闭,隔水加热至酒吸尽,取出,与上述稠膏混合,干燥,粉碎成细粉,过筛,混匀。每 100g 粉末加炼蜜 170～200g 制成大蜜丸。每丸重 9g。这一制备方法一直延续到 2005 年。功能主治:祛风湿,利关节,解毒。用于风湿痹痛,筋骨无力,腰膝酸软,四肢麻痹,半身不遂,风疹湿疮。宋·《证类本草》中也收载有一个豨莶丸(即古方豨莶丸),为单一豨莶草的嫩茎叶,经用酒蒸制九次后制备成的蜜丸。主治中风,同时长服久服还可以强身健体。可见今方豨莶丸无古方豨莶丸的功效神奇。古方豨莶丸是如何演变成今方豨莶丸的无文献可查证。因此决定对今方豨莶丸进行配方优化实验,又由于临床常用豨莶丸治疗骨性关节炎病,因此优化实验完成后探讨了优化方治疗膝关节骨性关节炎的药效和作用机理。
本课题旨在探讨用文献学结合现代实验的方法解决炮制学中的相关问题的可行性,以单味中药生熟各半制成的中成药-豨莶丸为研究对象,运用文献学的方法对豨莶草和豨莶丸作多方面内容的考证,用药理实验结合化学实验的方法作豨莶草炮制前后的对比研究,以炮制前后药效和成分方面的变化作为依据,用直接实验设计法对今方豨莶丸进行配方优化的实验研究,对通过优化研究组成的新方进行主要药效学研究及作用机理的探讨。
本研究实验分为三部分。
2 豨莶丸的配方优化及对实验性膝骨性关节炎的药效及作用机理探讨
1 文献考证
1.1 目的
由于今方和古方豨莶丸在配方功效方面存有差异,因此对豨莶草原植物来源、
入药部位、炮制历史沿革及 古方豨莶丸的制备和应用进行文献学考证,找出今方和
古方豨莶丸的相关背景资料。
1.2 结果
对豨莶草考证的结果表明:
⑴古代当时至少有三种植物当成豨莶草药用, ①是名为火杴的植物,经考证应
为茄科植物龙葵;②是名为猪膏草的植物,经考证为菊科植物腺梗豨莶,为现代豨
莶草原植物之一;③是名为地菘的植物,经考证为茄科植物天明精,是有毒植物,
为现代中药鹤虱的原植物。正品豨莶草应为腺梗豨莶,天明精及龙葵均为混淆品,
不能做豨莶草用。至于从 1977 年版药典起开始收载的豨莶和毛梗豨莶则为现代扩大
药源时加入的品种,与腺梗豨莶同科同属,经化学及药理实验证明与腺梗豨莶相似 。
⑵古代豨莶草只以嫩茎叶入药,粗茎属于非入药部分要求除掉。
⑶古文献中记载豨莶草的炮制方法有清蒸、酒蜜蒸、酒蒸、酒炒、清炒。蒸法
中无论用辅料或不用辅料都要求蒸九次,并有强调不蒸够九次,疗效不好。
⑷豨莶草酒蒸制九次矫臭矫味,气味香美,转寒为温,活血祛风之性未改,而
温养之力更加,甚益元气,祛风逐湿之中,有补益肝肾之功,可以长服久服。适用
于肝肾虚而肾又犯风邪湿气患者,既可使邪风去又可使肝肾能较好地恢复功能。
⑸豨莶草生熟异用总结为:生用与制用,其药性与功效有别。生用或制用,均
可祛风湿、舒筋活络,但以炮制品之辛散温通力稍强,兼有补益肝肾的作用,用于
风湿痹证,骨节疼痛,或麻木拘挛者。治疮痈肿毒,取其清热解毒之功;治湿疹痒
疮,取其除湿止痒之功,宜生用。
对豨莶丸考证的结果表明:
(1)豨莶丸最早出处应是宋·《证类本草》卷十一引成纳方,而不是《中医学
大辞典》中记载的“出于《严氏济生方》”。
(2)古方豨莶丸为单一豨莶草的嫩茎叶,经用酒蒸制九次后制备的蜜丸。而今
方豨莶丸处方是生豨莶草粗茎与用酒蒸制后的嫩茎叶各一半。
(3)古方豨莶丸的功能主治主要是祛风除湿,通痹止痛,长精神,健体强身。
主治风湿痹病,关节疼痛,筋骨无力,腰膝酸软及中风引起的半身不遂,肢体麻木,
久服养精神,美容颜。今方豨莶丸清热祛湿,散风止痛。用于风湿热阻络所致的痹
病,症见肢体麻木、腰膝酸软
Processing drugs is a traditional pharmacy technology based on the traditional theories, the requirements of treatment, the quality nature of drugs and the different demands of dispensing. Traditional Chinese medicine (TCM) will strengthen its effect and degrade its toxicity by processing. There are many processing drugs which change their effects by processing are recorded in various ancient literatures such as rough Shengdi and processed Shengdi, rough Xijian and processed. However there are some difference between the traditional and contemporary processing methods and aims. In order to solve these problems, a lot of literature research and experiments are needed.
Xijian herb is a kind of annual herb recorded first in the XIN XIU BEN CAO. According to traditional theories rough Xijian mainly aims at clearing liver-heat and toxic material and is used to cure furuncle, rubella, eczema and so on. When Xijian is processed with alcohol, it has the effects of eliminating rheumatism, strengthening bones and muscles, and making up liver and kidney . Then it is used to cure palsy, rheumatic and so on.
Xijian pill has been recorded in the Chinese Pharmacopoeia from 1963. The pill preparative method in Pharmacopoeia differs in the traditional one. So this study aims at probing the possibility of solving the problems of processing drugs with literature research and contemporary experiments. Our work began with literature review of Xijian herb and Xijian pill. Then we compared the effects and ingredients of rough Xijian and processed Xijian. Furthermore we optimized the prescription and discussed the mechanism.
1. Literature researsh Motive
Because of the difference between traditional and contemporary effects, we reviewed the plant origin, applying part, processing history, preparation and application of Xijian in order to collect the background information of Xijian pill.
Result
Contemporary applying part and the processing method of Xijian are different from traditional ones. When it comes to the effects and prescription, there still are some differences between traditional and contemporary Xijian. At the some time, the effects of rough Xijian and processed Xijian are also different.
2 Processing HERBA SIEGESBECKIAE of drug action and chemical composition to contrast and study in circa . 2.1 Motive XIJIAN pill rough product and processed product for antiinflammatory anti-rheumatism and chemical composition to contrast and study to reveal processed product HERBA SIEGESBECKIAE chang in drug action and ingredient 2.2 Test methods and Result processed product HERBA SIEGESBECKIAE have apparently depressant effec to Acute inflammation chronic inflammation and immunity inflammation.it better thanrough product. acute toxicity test presentation of resultsrough product and processed product is innocuity ;thin layer chromatography convict rough product andprocessed product have much difference. 2.3 Conclusion HERBA SIEGESBECKIAE rough product and processed product have much difference in drug action and chemicial composition. 3 To make use of direct design of experiment method grading-up XIJIAN pill prescription. 3.1 Motive With drug action and chemical index to find best prescription and suitable dosage. 3.2 Method To use direct design of experiment method .tow factors are rough pachy stem and wine parboil tender stem.to set up seven levels.Then applying RDZ software compute.we can get a plan that need seven time experiments. We Select IL-1βand IL-6 synovial fluid for chemicial index that judge immunity inflammation and pathogenetic condition severity.the same time we shoose nonanol that is composition of HERBA SIEGESBECKIAE. Nonanol contents is pharmacodynamics foundational index to get grading-up prescription 3.3 Result The best prescription: rough pachy stem 0g ;wine parboil tender stem 30g. 4 To probe grading-up XIJIAN pill prescription treat ostarthritis of drug efficacy study and mechanism of action. 4.1 Motive With pharmacodynamics immunology histomorphology to sure the depressant effect to infl.and find t
引文
[1] 王洪飞,让文化瑰宝焕发异彩-“中药复方再优化”研究的思考, 首都医药,2001,8(6):17～18
[2] 侯素春等,不同剂量凉血活血复方对小鼠上皮细胞增殖、表皮细胞分化、血浆 ET-1 及血清 sE-selectin 的影响, 无出处
[3] 李力等,复方地龙胶囊组方与制备工艺研究,药学进展,2000,24(6):358～361
[4] 朱双秋、刘蕾等,麻黄汤不同配伍对乙酰胆碱致豚鼠离体气管痉挛的抑制,黑龙江医药科学,2003,26(6):10～11
[5] 袁媛等,丹七制剂提取工艺的优化实验研究,华西药学杂志,2002,17(1):10～12
[6] 易毛等,复方鳖甲软肝片提取工艺的优化,华西药学杂志,2001,16(6):471～472
[7] 何明等,胃舒宝和月舒贴的研制,世界中西医结合大会论文集 143 页
[8] 白海波等,正交设计-重复试验法优选赤芍的提取工艺,中国实验方剂学杂志,2002,8(4):16:17
[9] 孟杰等,正交试验法分析复方参仙生脉饮的配伍关系,中国中药杂志 2000,25(5):308～310)
[10] 张福良等,均匀设计在白术提取工艺的优化,大连医科大学学报 1999,21(4):307～308
[11] 林桂涛等,灰色系统理论与均匀设计结合在补阳还五汤处方筛选中的应用,中国实验方剂学杂志,1997,3(4):16～20
[12] 盛海林等,球面对称设计在药剂学上的应用,中国药科大学学报,1996,27(4):211～214
[13] 刘强、周莉玲等,球面对称设计法筛选青藤碱贴片中的透皮吸收促进剂,中国中药杂志,1999,24(8)467～470
[14] 吴婉莹、李云谷,金雀异黄素壳聚糖微球的制备方法,中国中药杂志,2002,27(5):353～355
[15] 吴云娟等,星点设计-效应面优化法优化三七总皂苷鼻腔用粉雾剂,中成药,2005,27(1):10～15
[16] 王洪飞等,DED 技术用于中药复方的全方药物筛选及优化的方案设计,北京中医药大学学报,1999,22(3);28～31
[17] 孙仲怡等,复方厚朴片生产工艺实验研究的优化方法,数理统计与管理 1996,15(6):21～25
[18] 商洪才等,一种适用于中药小复方配比优选设计方法的建立,中国实 验方剂学杂志 2003,9(3):1～3
[19] 商洪才等,丹参/三七不同配比药效学比较研究——对急性实验性心肌缺血犬心肌生化标志物的影响[J],天津中医,2002,19(2):43
[2] 侯素春等,不同剂量凉血活血复方对小鼠上皮细胞增殖、表皮细胞分化、血浆 ET-1 及血清 sE-selectin 的影响, 无出处
[3] 李力等,复方地龙胶囊组方与制备工艺研究,药学进展,2000,24(6):358～361
[4] 朱双秋、刘蕾等,麻黄汤不同配伍对乙酰胆碱致豚鼠离体气管痉挛的抑制,黑龙江医药科学,2003,26(6):10～11
[5] 袁媛等,丹七制剂提取工艺的优化实验研究,华西药学杂志,2002,17(1):10～12
[6] 易毛等,复方鳖甲软肝片提取工艺的优化,华西药学杂志,2001,16(6):471～472
[7] 何明等,胃舒宝和月舒贴的研制,世界中西医结合大会论文集 143 页
[8] 白海波等,正交设计-重复试验法优选赤芍的提取工艺,中国实验方剂学杂志,2002,8(4):16:17
[9] 孟杰等,正交试验法分析复方参仙生脉饮的配伍关系,中国中药杂志 2000,25(5):308～310)
[10] 张福良等,均匀设计在白术提取工艺的优化,大连医科大学学报 1999,21(4):307～308
[11] 林桂涛等,灰色系统理论与均匀设计结合在补阳还五汤处方筛选中的应用,中国实验方剂学杂志,1997,3(4):16～20
[12] 盛海林等,球面对称设计在药剂学上的应用,中国药科大学学报,1996,27(4):211～214
[13] 刘强、周莉玲等,球面对称设计法筛选青藤碱贴片中的透皮吸收促进剂,中国中药杂志,1999,24(8)467～470
[14] 吴婉莹、李云谷,金雀异黄素壳聚糖微球的制备方法,中国中药杂志,2002,27(5):353～355
[15] 吴云娟等,星点设计-效应面优化法优化三七总皂苷鼻腔用粉雾剂,中成药,2005,27(1):10～15
[16] 王洪飞等,DED 技术用于中药复方的全方药物筛选及优化的方案设计,北京中医药大学学报,1999,22(3);28～31
[17] 孙仲怡等,复方厚朴片生产工艺实验研究的优化方法,数理统计与管理 1996,15(6):21～25
[18] 商洪才等,一种适用于中药小复方配比优选设计方法的建立,中国实 验方剂学杂志 2003,9(3):1～3
[19] 商洪才等,丹参/三七不同配比药效学比较研究——对急性实验性心肌缺血犬心肌生化标志物的影响[J],天津中医,2002,19(2):43