中药六类新药黄柏治糜栓的研究
摘要
本文以六味药材共同起效为目的,研究制备了六类新药—黄柏治糜栓。在中药提取方面,采用正交实验法,分别以黄柏中盐酸小檗碱的量为指标,对黄柏、紫草乙醇提取的最佳工艺进行了考察;以苦参中氧化苦参碱的量为指标,对其余药材和醇提后的黄柏、紫草残渣水煎煮提取及水煎醇沉提取的最佳工艺进行了考察。在制剂成型工艺方面,筛选了适用的辅料,并对制剂成型工艺进行了研究。在质量标准方面,定性研究采用TLC法对制剂中的黄柏、蒲公英、紫花地丁三味药材进行了鉴别;定量研究采用HPLC法对制剂中氧化苦参碱进行了方法学考察和含量测定,并制定了本制剂的含量限度。在制剂稳定性方面,分别对制剂的定性鉴别、含量测定、检查等项进行了考察,常温试验考察了12个月,目前仍在继续考察;加速试验考察了3个月。通过本课题的研究,提供了黄柏治糜栓制备工艺、质量标准、含量测定、稳定性考察等方面药学部分的资料,为申报该新药品种药学部分奠定了基础。
Huangbai zhimi Uppository is a kind of preparation composed of Traditional Chinese Medicine (TCM). It developed from effective prescription of TCM after properly disposed according to pharmacological results and clinical practices. The uppository is prepared by extracts from six kinds of TCM, Amur Corktree Bark、Taraxacum、Purpleflower Violet、Arnebia Root、Lightyellow sophora root and Dragon’s Blood, all recorded in the Chinese Pharmacopoeia. The preparation is organized reasonable and creatively used to cure cervical erosion.
The main aim of this dissertation is to study the preparation procedure and quality control standards of Huangbai zhimi Uppository. Selecting uppository as the preparation form, the dissertation included preparation procedure, quality control, stability research and others by preliminary examinations. The results are as follows.
A. The preparation procedure
1. Studying the alcohol extraction technics of Amur Corktree Bark and Arnebia Root by testing the content of berberine hydrochloride. The optimum alcohol concentration was studied firstly. Then selecting extraction time, extraction times and the alcohol amount as the investigating factors, the optimum preparation procedure was studied by orthogonal text. The reasonable and available process conditions were established.
2. Studying the water extraction technics of other drugs and remainder of Amur Corktree Bark and Arnebia Root after alcohol extraction by testing extract content and the content of ammothamnine. Selecting the water amount, decoction time, decoction times and error as the investigating factors, the optimum preparation procedure was studied by orthogonal text. The reasonable and available process conditions were established.
3. Studying the water extraction-alcohol deposition technics of drugs by testing extract content and the content of ammothamnine. Selecting relative density of the liquor and alcohol concentration as the investigating factors, the optimum preparation procedure was studied by orthogonal text. The reasonable and available process conditions were established.
B. The molding preparation procedure
The kinds and usage amount of dressing and other aspects were studied in detail. The optimum preparation procedure was established.
C. The quality standards research
The qualitative TLC and quantitative HPLC research were well studied in the dissertation.
Amur Corktree Bark、Purpleflower Violet and taraxacum were identified by TLC. The experimental results suggested that the spots on the chromatograms are clear, characteristic, reproducibility, and without interference by negative material. The methods are applicable to controll the standards of Huangbai zhimi Uppository.
The contend of Ammothamnine was determined by HPLC. The experimental results suggested that their linearity, precision, reproducibility, recovery are all satisfactory. Their content limits were both regulated: the content of Ammothamnine is no less than 0.14mg per pill, respectively.
D. The stability research
In the preparation stable aspect, used the normal temperature test and the acceleration test to the preparation character outward appearance, the load difference, the disintegration time limit, the microorganism limit, the qualitative distinction, the content determination item has separately carried on the inspection. The normal temperature test inspected for 12 months, the acceleration test inspected for 3 months, the results not obviously changed, showed the preparation stable in the storage time, the stability was good.
The results showed that the preparation procedure of Huangbai zhimi Uppository is reasonable in technics, controllable in quality and good in stability. The thesis provided whole pharmaceutical document for the declaration of Huangbai zhimi Uppository.
Huangbai zhimi Uppository is a kind of preparation composed of Traditional Chinese Medicine (TCM). It developed from effective prescription of TCM after properly disposed according to pharmacological results and clinical practices. The uppository is prepared by extracts from six kinds of TCM, Amur Corktree Bark、Taraxacum、Purpleflower Violet、Arnebia Root、Lightyellow sophora root and Dragon’s Blood, all recorded in the Chinese Pharmacopoeia. The preparation is organized reasonable and creatively used to cure cervical erosion.
The main aim of this dissertation is to study the preparation procedure and quality control standards of Huangbai zhimi Uppository. Selecting uppository as the preparation form, the dissertation included preparation procedure, quality control, stability research and others by preliminary examinations. The results are as follows.
A. The preparation procedure
1. Studying the alcohol extraction technics of Amur Corktree Bark and Arnebia Root by testing the content of berberine hydrochloride. The optimum alcohol concentration was studied firstly. Then selecting extraction time, extraction times and the alcohol amount as the investigating factors, the optimum preparation procedure was studied by orthogonal text. The reasonable and available process conditions were established.
2. Studying the water extraction technics of other drugs and remainder of Amur Corktree Bark and Arnebia Root after alcohol extraction by testing extract content and the content of ammothamnine. Selecting the water amount, decoction time, decoction times and error as the investigating factors, the optimum preparation procedure was studied by orthogonal text. The reasonable and available process conditions were established.
3. Studying the water extraction-alcohol deposition technics of drugs by testing extract content and the content of ammothamnine. Selecting relative density of the liquor and alcohol concentration as the investigating factors, the optimum preparation procedure was studied by orthogonal text. The reasonable and available process conditions were established.
B. The molding preparation procedure
The kinds and usage amount of dressing and other aspects were studied in detail. The optimum preparation procedure was established.
C. The quality standards research
The qualitative TLC and quantitative HPLC research were well studied in the dissertation.
Amur Corktree Bark、Purpleflower Violet and taraxacum were identified by TLC. The experimental results suggested that the spots on the chromatograms are clear, characteristic, reproducibility, and without interference by negative material. The methods are applicable to controll the standards of Huangbai zhimi Uppository.
The contend of Ammothamnine was determined by HPLC. The experimental results suggested that their linearity, precision, reproducibility, recovery are all satisfactory. Their content limits were both regulated: the content of Ammothamnine is no less than 0.14mg per pill, respectively.
D. The stability research
In the preparation stable aspect, used the normal temperature test and the acceleration test to the preparation character outward appearance, the load difference, the disintegration time limit, the microorganism limit, the qualitative distinction, the content determination item has separately carried on the inspection. The normal temperature test inspected for 12 months, the acceleration test inspected for 3 months, the results not obviously changed, showed the preparation stable in the storage time, the stability was good.
The results showed that the preparation procedure of Huangbai zhimi Uppository is reasonable in technics, controllable in quality and good in stability. The thesis provided whole pharmaceutical document for the declaration of Huangbai zhimi Uppository.
引文
[1] 山东省人民医院主编《实用妇科学》.山东:山东人民出版社,1976:173
[2] 冀绪.浅谈带脉理论在带下病中的作用.河北中医,1997,19(2):33
[3] 杨家林.带下病病机及证治.四川中医,1986,2(3):7
[4] 浦永芬.带下病从瘀论治初探.贵阳中医学院学报,2001,4(3):11-13
[5] 罗元恺. 女科述要.新中医,1992,(9):153-155
[6] 吴宏光,吴熙伯. 从肝论治带下病.广西中医药,1986,(05)
[7] 金凤平,杨茂丁.荆羌芷蚕汤治疗带下病 226 例.陕西中医,2001,22 (11):653-654
[8] 赵建群. 升阳益胃汤加减治疗带下病 74 例.河北中医,2000,22(4):288
[9] 时燕萍. 大黄珍珠散治疗宫颈炎33例.湖北中医杂志,2004,(11)
[10] 宋国钟. 中药宫糜散治疗宫颈糜烂 80 例.中医外治杂志,2001,(05)
[11] 刘兰香,张元顺. 月宫栓治疗宫颈糜烂 360 例疗效观察.新中医,2002,(03)
[12] 沙玉琴. 生肌油治疗宫颈糜烂 106 例 .陕西中医 ,2002,(05)
[13] 张丽君. 自拟宫糜散治疗宫颈糜烂 60 例疗效观察.安徽中医临床杂志,2001,(02)
[14] 钱 晓 伟 . 消 糜 栓 治 疗 宫 颈 糜 烂 效 果 临 床 观 察 . 海 峡 药学,2005,17(2):108-109
[15] 和国英. 中药内外合治治疗带下病 46 例疗效观察.云南中医中药杂志, 2003,24(6):13-14
[16] 蒋国玲. 坐浴并置妇炎栓治疗宫颈糜烂 63 例体会.甘肃中医,2001,14(4):54-55
[17] 周萍,王丽华. 电熨治疗慢性宫颈炎 1860 例临床观察.中国临床医药研究杂志,2004,131:49-49
[18] 赵昀,崔淑慧,任丽华,赵超,魏丽惠. 阴道镜下宫颈“糜烂”表现及冷冻治疗的临床研究.中国妇产科临床杂志,2007,8(4):256-258
[19] 王艳华. 激光治疗宫颈糜烂 157 例疗效观察.中国当代医学,2006,5(24):71-71
[20] 罗佩清. 微波治疗宫颈糜烂 189 例疗效观察.华夏医学,2006,19(4):763-764
[21] 汪玉琴. 波姆光治疗宫颈糜烂 880 例临床总结.中华医学实践杂志,2005,4(9):925-926
[22] 张娅丽,曲君. 红外线凝结法治疗宫颈糜烂 68 例的疗效分析.中华现代妇产科学杂志,2005,2(7):653-654
[23] 禹爱琴,岳青芬,李玲玲. 高频电波刀电圈切除术治疗宫颈病变临床观察.中原医刊,2007,34(5):58-58
[24] 韩英,丁岩,马俊旗,祖菲娅·艾力,古丽娜·阿,王玉瑛. 宫腔镜下宫颈电切术在宫颈病变诊断和治疗中的价值.新疆医科大学学报,2006,29(5):385-388
[25] Kennett BB. Deep loop exsision for pehy sterectomy endocerviacal evaluation. American Journal of Obstetrics and Gynecology,1997,176:82-92
[26] 梁晶. α-干扰素栓与爱宝疗栓治疗宫颈糜烂疗效比较.安徽医药,2006,10(12):918-918
[27] jintao wang,ersheng gao,ling ding,yuying cheng. Association between endogenous hormones, hormone receptors and cervical cancer. Chinese Journal of Oncology.2006,7
[28] 王衡奇,秦民坚,余国奠. 黄柏的化学成分及药理学研究进展.中国野生植物资源 ,2001,20(04):6-8
[29] 赵华,游勇基. 紫草药材化学成分的测定.海峡药学,2007,19(04):35-38
[30] 许 丹,侯凤飞,吴立军,康廷国. 蒲公英的化学研究.中国中药杂志, 2004,29(03)
[31] 浦永芬,杨在纲. 紫花地丁的有效成分分析及抗菌作用研究.中兽医医药杂志,2004,23(03):16-18
[32] 苗抗立,张建中等. 苦参的化学成分及药理的研究进展.天然产物研究与开发, 2001,13(02):69-73
[33] 裴宗弟.龙血竭的化学成分的鉴别.黑龙江医药,2006,19(06):429-430
[2] 冀绪.浅谈带脉理论在带下病中的作用.河北中医,1997,19(2):33
[3] 杨家林.带下病病机及证治.四川中医,1986,2(3):7
[4] 浦永芬.带下病从瘀论治初探.贵阳中医学院学报,2001,4(3):11-13
[5] 罗元恺. 女科述要.新中医,1992,(9):153-155
[6] 吴宏光,吴熙伯. 从肝论治带下病.广西中医药,1986,(05)
[7] 金凤平,杨茂丁.荆羌芷蚕汤治疗带下病 226 例.陕西中医,2001,22 (11):653-654
[8] 赵建群. 升阳益胃汤加减治疗带下病 74 例.河北中医,2000,22(4):288
[9] 时燕萍. 大黄珍珠散治疗宫颈炎33例.湖北中医杂志,2004,(11)
[10] 宋国钟. 中药宫糜散治疗宫颈糜烂 80 例.中医外治杂志,2001,(05)
[11] 刘兰香,张元顺. 月宫栓治疗宫颈糜烂 360 例疗效观察.新中医,2002,(03)
[12] 沙玉琴. 生肌油治疗宫颈糜烂 106 例 .陕西中医 ,2002,(05)
[13] 张丽君. 自拟宫糜散治疗宫颈糜烂 60 例疗效观察.安徽中医临床杂志,2001,(02)
[14] 钱 晓 伟 . 消 糜 栓 治 疗 宫 颈 糜 烂 效 果 临 床 观 察 . 海 峡 药学,2005,17(2):108-109
[15] 和国英. 中药内外合治治疗带下病 46 例疗效观察.云南中医中药杂志, 2003,24(6):13-14
[16] 蒋国玲. 坐浴并置妇炎栓治疗宫颈糜烂 63 例体会.甘肃中医,2001,14(4):54-55
[17] 周萍,王丽华. 电熨治疗慢性宫颈炎 1860 例临床观察.中国临床医药研究杂志,2004,131:49-49
[18] 赵昀,崔淑慧,任丽华,赵超,魏丽惠. 阴道镜下宫颈“糜烂”表现及冷冻治疗的临床研究.中国妇产科临床杂志,2007,8(4):256-258
[19] 王艳华. 激光治疗宫颈糜烂 157 例疗效观察.中国当代医学,2006,5(24):71-71
[20] 罗佩清. 微波治疗宫颈糜烂 189 例疗效观察.华夏医学,2006,19(4):763-764
[21] 汪玉琴. 波姆光治疗宫颈糜烂 880 例临床总结.中华医学实践杂志,2005,4(9):925-926
[22] 张娅丽,曲君. 红外线凝结法治疗宫颈糜烂 68 例的疗效分析.中华现代妇产科学杂志,2005,2(7):653-654
[23] 禹爱琴,岳青芬,李玲玲. 高频电波刀电圈切除术治疗宫颈病变临床观察.中原医刊,2007,34(5):58-58
[24] 韩英,丁岩,马俊旗,祖菲娅·艾力,古丽娜·阿,王玉瑛. 宫腔镜下宫颈电切术在宫颈病变诊断和治疗中的价值.新疆医科大学学报,2006,29(5):385-388
[25] Kennett BB. Deep loop exsision for pehy sterectomy endocerviacal evaluation. American Journal of Obstetrics and Gynecology,1997,176:82-92
[26] 梁晶. α-干扰素栓与爱宝疗栓治疗宫颈糜烂疗效比较.安徽医药,2006,10(12):918-918
[27] jintao wang,ersheng gao,ling ding,yuying cheng. Association between endogenous hormones, hormone receptors and cervical cancer. Chinese Journal of Oncology.2006,7
[28] 王衡奇,秦民坚,余国奠. 黄柏的化学成分及药理学研究进展.中国野生植物资源 ,2001,20(04):6-8
[29] 赵华,游勇基. 紫草药材化学成分的测定.海峡药学,2007,19(04):35-38
[30] 许 丹,侯凤飞,吴立军,康廷国. 蒲公英的化学研究.中国中药杂志, 2004,29(03)
[31] 浦永芬,杨在纲. 紫花地丁的有效成分分析及抗菌作用研究.中兽医医药杂志,2004,23(03):16-18
[32] 苗抗立,张建中等. 苦参的化学成分及药理的研究进展.天然产物研究与开发, 2001,13(02):69-73
[33] 裴宗弟.龙血竭的化学成分的鉴别.黑龙江医药,2006,19(06):429-430