中药五类新药康心通脉胶囊的研究
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摘要
本文从中医药学和药理学的角度论述了中赤芍和槐米作为治疗冠心病药物的理论和实验依据。为了克服传统中药剂型的缺点,本文以药赤芍和槐米的有效部位为原料药研究制备了五类新药--康心通脉胶囊。并在此基础上申请了发明专利。在制剂工艺方面:首先,通过正交实验确定了赤芍总苷和槐米总黄酮的最佳提取工艺;其次,确定了选用的辅料、对成型工艺进行了研究。在质量标准方面:为药材,辅料,原料药和制剂建立了质量标准,以芍药苷和芦丁为指标,运用高效液相色谱方法分别对原料药赤芍总苷、槐米总黄酮和制剂进行含量考察。为康心通脉胶囊的质量可控、含量可测、疗效可靠奠定基础。
“Kangxintongmai” is a scientific-researching recipe with thepurpose of activating the blood circulation, digesting the extravasatedblood,dredging the the blood vessel and relieving the pain. It iscomposed by total glucosides of red paeony root(TGRP) and totalflavone of Pagodatree Flower Bud(TPPB). The former is primarymedicine with the function of clearing the foul blood and relieving thepain,the latter is subsidiary medicine with the function of cooling theblood.Suitable usage of the tow can cool the blood and drege thevessel,then the pain of heart will relieve.
The pharmic affection of the formular shows that “Kangxintong-mai” can expand coronary artery,resist the coronary atherosclerotic,relieve the pain and lower the oxygen-consumption of cardiac muscle.
Traditional medicine dosage forms are mainly soup, pill, powder,ointment and small pill. inpress people its coarseness, bigness,blackness. on the contrary to western medicine, its bulk is bigger,coller is worse, smell is not better, and it is difficult to carry, to takeand it is slow to be absorbed. In order to overcome this disadvantage,lots of experts in pharmacy alternate the traditional medicine dosageforms with introducing many dosahge forms of western medicine. Inthis paper, kangxintongmai capsule---the new dosage of traditionalmedicine was developed with active parts of chishao(Red PaeonyRoot)and huaimi (Pagodatree Flower Bud)) as raw medicinal materials.Herein, patent for kangxintongmai capsule was applied for.
According to the optimal results of orthogonal design experimenton extract process of chishao, extract powder was obtained by treatingwater-boiled liquid through macroporous resin with 20% alcohol aseluent and then evaporating the extract with vacuum. Herein, an activeconstituent liquiritin was isolated from extract powder by columnchromatography method. Then, According to the optimal results oforthogonal design experiment on extract process of huaimi, extractpowder was obtained by dissolve with alkaline water and thenprecipitated with acid water and then evaporating the extract withvacuum after the herb was boiled with 80% alcohol.The reasonableness and stability of the pharmaceutical technologyare proved by the research of pharmacodynamics contrast experimentand the middle scale production on the basis, using advanced analyticaltechnique the quality standard of the medicineis studied and thequality-controlling program is laid down. Through those above-mentioned rese-arches, the total pharmaceutical work before clinic research fixed thesecond class new traditional Chinese medicine stipulate in "The Methodsof Examining and Approving NewMedicine"
“Kangxintongmai” is a scientific-researching recipe with thepurpose of activating the blood circulation, digesting the extravasatedblood,dredging the the blood vessel and relieving the pain. It iscomposed by total glucosides of red paeony root(TGRP) and totalflavone of Pagodatree Flower Bud(TPPB). The former is primarymedicine with the function of clearing the foul blood and relieving thepain,the latter is subsidiary medicine with the function of cooling theblood.Suitable usage of the tow can cool the blood and drege thevessel,then the pain of heart will relieve.
The pharmic affection of the formular shows that “Kangxintong-mai” can expand coronary artery,resist the coronary atherosclerotic,relieve the pain and lower the oxygen-consumption of cardiac muscle.
Traditional medicine dosage forms are mainly soup, pill, powder,ointment and small pill. inpress people its coarseness, bigness,blackness. on the contrary to western medicine, its bulk is bigger,coller is worse, smell is not better, and it is difficult to carry, to takeand it is slow to be absorbed. In order to overcome this disadvantage,lots of experts in pharmacy alternate the traditional medicine dosageforms with introducing many dosahge forms of western medicine. Inthis paper, kangxintongmai capsule---the new dosage of traditionalmedicine was developed with active parts of chishao(Red PaeonyRoot)and huaimi (Pagodatree Flower Bud)) as raw medicinal materials.Herein, patent for kangxintongmai capsule was applied for.
According to the optimal results of orthogonal design experimenton extract process of chishao, extract powder was obtained by treatingwater-boiled liquid through macroporous resin with 20% alcohol aseluent and then evaporating the extract with vacuum. Herein, an activeconstituent liquiritin was isolated from extract powder by columnchromatography method. Then, According to the optimal results oforthogonal design experiment on extract process of huaimi, extractpowder was obtained by dissolve with alkaline water and thenprecipitated with acid water and then evaporating the extract withvacuum after the herb was boiled with 80% alcohol.The reasonableness and stability of the pharmaceutical technologyare proved by the research of pharmacodynamics contrast experimentand the middle scale production on the basis, using advanced analyticaltechnique the quality standard of the medicineis studied and thequality-controlling program is laid down. Through those above-mentioned rese-arches, the total pharmaceutical work before clinic research fixed thesecond class new traditional Chinese medicine stipulate in "The Methodsof Examining and Approving NewMedicine"
引文
[1] 陈波等.冠心病[M].赤峰.内蒙古科学技术出版社 2002,1-5
[2] 王丰宝.冠心病的中医辨证论治[J].医药产业资讯,2005,2 (12):115-116
[3] 李胜涛.李富春教授治疗冠心病纂要[J].四川中医.2004,22 (8):2-3
[4] 李胜涛.李富春教授治疗冠心病纂要[J].四川中医.2004,22 (8):2-3
[5] 李月华等.冠心病患者临床表现、血压及血脂水平与血清 c反应蛋白的关系[J].中国临床康复,2005,9(27):36-37
[6] 晁兰芳等.老年冠心病患者猝死诱因分析及护理[J].菏泽医学专科学校学报,2003,15(4):21
[7] 许慧敏.冠心病发病因素的调查[J].山西科技,2004(6):88
[8] 王永宁等.糖尿病并发冠心病危险因素分析[J].陕西医学杂志,2003,32(9):845-846
[9] 孟昭琴等.冠心病患者的危险因素与运动疗法[J].中国临床康复,2003,7(30):4140
[10] 国家药典编写委员会.中华人民共和国药典(2005年版)·一部[M].北京:化学工业出版社2005:109
[11] 杨榆等.正交实验法优选赤芍的渗漉提取工艺[J].医药导报,2005,24(5):433-434
[12] 安玉秀.正交实验优选赤芍水煎提取工艺[J].齐鲁药事,2005,24(9):54-55 国实验方剂学杂志,2002,8(4):16
[14] 张春晓.赤芍中芍药苷提取工艺研究[J].辽宁中医学学报, 2002,4(1):24
[15] 邓一鸣等。赤芍中芍药苷的提纯工艺研究[J].南京中医药大学学报,2004,20(6):363364
[16] 何丽娜,杨军,何素冰等.赤芍总苷对原代培养大鼠神经细胞损伤模型的保护作用[J].中国临床药理学与治疗学杂志,2000,5( 1):28-31
[17] 刘超,王静,杨军.赤芍总甙活血化瘀作用的研究[J].中药材 ,2000;23(9):557～560
[18] 李文,殷小杰,廖福龙.六种产地赤芍对大鼠抗凝血及抗血小板聚集作用的比较[J].中国实验方剂学杂志,2001,7(6):30～31
[19] 徐红梅等.赤芍总苷抗血栓作用研究[J].安徽中医学院学报,2000,19(1):46-47
[20] 于永红,王瑞英.赤芍、尼群地平对家兔实验性动脉粥样硬化病灶的消退作用[J].临床心血管病杂志,1996,12(3):164～16
[21] 楚正绪,谭建权,张亚霏.赤芍提取物对烫伤大鼠早期心肌力学的影响[J].中成药,1989,12(7):23～27
[22] 莫晓燕、黄海霞、洪喻. 赤芍总苷对培养乳鼠心肌细胞损伤的抗氧化作用[J].中国药理学通报,2004,20(10):1119～1121
[23] 杨军等.赤芍总苷对小鼠脑缺血再灌注损伤的保护作用[J].中药材,2000,23(2):94-97
[24] 阮金兰、赵钟祥、曾庆忠等.赤芍化学成分和药理作用的研究进展[J],中国药理学通报.2003,19(9):965～970
[25]《中国药物大全》编辑委员会.中国药物大全·中药类[M]. 北京:人民卫生出版社1999,228-229
[26] 中华人民共和国卫生部.中华人民共和国药典·一部[M].北京:化学工业出版社1992,311-312
[27] 战玉琴.冷碱法从槐米中提取芦丁的实验研究[J].中成药, 1994,16(7):10
[28] 郁建平等.大孔吸附树脂提取荞麦芦丁工艺研究[J].贵州农业科学,1997,25(2):3～8
[29] 王昌利等.超声提取芦丁得率的实验研究[J].中成药,1993, 15(2)7-8
[30] 林翠英.芦丁超声提取新技术的再探索[J].中草药,1999, 30(5):350-351
[31] 陈庶来,陈洁.用超临界 CO2 从槐花米中提取芦丁试验研究[J].江苏理工大学学报,1996,17(4):7～9
[32] 陈雨亭等.芸香苷等天然产物清除活性氧自由基02 -和·OH的ESR研究生物物理学报,1989,5(3):239-240
[33] 夏维木等.应用 SER 技术观察芦丁对 02 -的清除作用[J].第二军医大学学报,1997,18(4):388-389
[34] 阎道广等.槲皮素和芦丁对 Fe2+和 Cu2+诱导的低密度脂蛋白 氧 化 修 饰 抑 制 作 用 的 比 较 研 究 [J]. 中 国 动 脉 硬 化 杂志,1995,3(2,会议专辑):190
[35] 阎道广等.槲皮素、芦丁和 BHT 对低密度脂蛋白氧化修饰的抑制效应[J].第一军医大学学报,1995,15(1):24～26
[36] 夏维木等.芦丁对肾脏缺血再灌注损伤保护作用的实验研究[J].中草药,1998,29(5):319-321
[37] 卢明珍等.芦丁对大鼠缺血再灌注心肌保护作用的研究[J]. 山西临床医学杂志,1999,8(1):10～12
[38] 陈文梅等.芦丁抑制家兔血小板激活因子诱导血小板活化作用的实验研究[J].中国中西医结合杂志,2002,22(4):283-285.
[2] 王丰宝.冠心病的中医辨证论治[J].医药产业资讯,2005,2 (12):115-116
[3] 李胜涛.李富春教授治疗冠心病纂要[J].四川中医.2004,22 (8):2-3
[4] 李胜涛.李富春教授治疗冠心病纂要[J].四川中医.2004,22 (8):2-3
[5] 李月华等.冠心病患者临床表现、血压及血脂水平与血清 c反应蛋白的关系[J].中国临床康复,2005,9(27):36-37
[6] 晁兰芳等.老年冠心病患者猝死诱因分析及护理[J].菏泽医学专科学校学报,2003,15(4):21
[7] 许慧敏.冠心病发病因素的调查[J].山西科技,2004(6):88
[8] 王永宁等.糖尿病并发冠心病危险因素分析[J].陕西医学杂志,2003,32(9):845-846
[9] 孟昭琴等.冠心病患者的危险因素与运动疗法[J].中国临床康复,2003,7(30):4140
[10] 国家药典编写委员会.中华人民共和国药典(2005年版)·一部[M].北京:化学工业出版社2005:109
[11] 杨榆等.正交实验法优选赤芍的渗漉提取工艺[J].医药导报,2005,24(5):433-434
[12] 安玉秀.正交实验优选赤芍水煎提取工艺[J].齐鲁药事,2005,24(9):54-55 国实验方剂学杂志,2002,8(4):16
[14] 张春晓.赤芍中芍药苷提取工艺研究[J].辽宁中医学学报, 2002,4(1):24
[15] 邓一鸣等。赤芍中芍药苷的提纯工艺研究[J].南京中医药大学学报,2004,20(6):363364
[16] 何丽娜,杨军,何素冰等.赤芍总苷对原代培养大鼠神经细胞损伤模型的保护作用[J].中国临床药理学与治疗学杂志,2000,5( 1):28-31
[17] 刘超,王静,杨军.赤芍总甙活血化瘀作用的研究[J].中药材 ,2000;23(9):557～560
[18] 李文,殷小杰,廖福龙.六种产地赤芍对大鼠抗凝血及抗血小板聚集作用的比较[J].中国实验方剂学杂志,2001,7(6):30～31
[19] 徐红梅等.赤芍总苷抗血栓作用研究[J].安徽中医学院学报,2000,19(1):46-47
[20] 于永红,王瑞英.赤芍、尼群地平对家兔实验性动脉粥样硬化病灶的消退作用[J].临床心血管病杂志,1996,12(3):164～16
[21] 楚正绪,谭建权,张亚霏.赤芍提取物对烫伤大鼠早期心肌力学的影响[J].中成药,1989,12(7):23～27
[22] 莫晓燕、黄海霞、洪喻. 赤芍总苷对培养乳鼠心肌细胞损伤的抗氧化作用[J].中国药理学通报,2004,20(10):1119～1121
[23] 杨军等.赤芍总苷对小鼠脑缺血再灌注损伤的保护作用[J].中药材,2000,23(2):94-97
[24] 阮金兰、赵钟祥、曾庆忠等.赤芍化学成分和药理作用的研究进展[J],中国药理学通报.2003,19(9):965～970
[25]《中国药物大全》编辑委员会.中国药物大全·中药类[M]. 北京:人民卫生出版社1999,228-229
[26] 中华人民共和国卫生部.中华人民共和国药典·一部[M].北京:化学工业出版社1992,311-312
[27] 战玉琴.冷碱法从槐米中提取芦丁的实验研究[J].中成药, 1994,16(7):10
[28] 郁建平等.大孔吸附树脂提取荞麦芦丁工艺研究[J].贵州农业科学,1997,25(2):3～8
[29] 王昌利等.超声提取芦丁得率的实验研究[J].中成药,1993, 15(2)7-8
[30] 林翠英.芦丁超声提取新技术的再探索[J].中草药,1999, 30(5):350-351
[31] 陈庶来,陈洁.用超临界 CO2 从槐花米中提取芦丁试验研究[J].江苏理工大学学报,1996,17(4):7～9
[32] 陈雨亭等.芸香苷等天然产物清除活性氧自由基02 -和·OH的ESR研究生物物理学报,1989,5(3):239-240
[33] 夏维木等.应用 SER 技术观察芦丁对 02 -的清除作用[J].第二军医大学学报,1997,18(4):388-389
[34] 阎道广等.槲皮素和芦丁对 Fe2+和 Cu2+诱导的低密度脂蛋白 氧 化 修 饰 抑 制 作 用 的 比 较 研 究 [J]. 中 国 动 脉 硬 化 杂志,1995,3(2,会议专辑):190
[35] 阎道广等.槲皮素、芦丁和 BHT 对低密度脂蛋白氧化修饰的抑制效应[J].第一军医大学学报,1995,15(1):24～26
[36] 夏维木等.芦丁对肾脏缺血再灌注损伤保护作用的实验研究[J].中草药,1998,29(5):319-321
[37] 卢明珍等.芦丁对大鼠缺血再灌注心肌保护作用的研究[J]. 山西临床医学杂志,1999,8(1):10～12
[38] 陈文梅等.芦丁抑制家兔血小板激活因子诱导血小板活化作用的实验研究[J].中国中西医结合杂志,2002,22(4):283-285.