脑得生软胶囊的药学研究
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摘要
脑得生片(丸)为传统中药制剂,收载于《中国药典》2005年版一部,由三七、川芎、红花、葛根、山楂五味中药组成,具有活血化瘀,通经活络。用于瘀血阻络所致的眩晕、中风,症见肢体不用、言语不利及头晕目眩;脑动脉硬化、缺血性中风及脑出血后遗症,临床应用广泛,疗效确切。本研究论文采用现代共性关键技术,对复方脑得生的提取纯化工艺、药物剂型改革、质量标准、药物的稳定性等进行了研究,旨在为脑得生制剂的二次开发提供科学依据。
采用溶剂法和大孔吸附树脂纯化技术,对脑得生复方中主要中药有效部位提取纯化工艺进行了研究,优选了最佳提取纯化工艺,取得了可靠的技术参数,进行了中试验证,可过渡到产业化;其提取物有效成分的总含量达到50%以上,符合国家食品药品监督管理局的相关规定。
在复方脑得生中药有效部位提取纯化工艺研究的基础上,对该复方的新剂型“脑得生软胶囊”的制剂工艺进行了研究,确定了囊芯液的制备、药物与辅料混悬、囊材制备、内容物与胶皮的相容性等技术参数,并进行了中试放大验证。其软胶囊成品合格率达94.3%。
采用现代分析方法,对脑得生软胶囊的性状、薄层鉴别、装量差异、崩解时限、含量测定等进行了系统研究,制订了该中药制剂较完善的质量标准。
采用加速试验的方法,对脑得生软胶囊的三批中试样品进行三个月的药物初步稳定性考察,按本品质量标准各项指标检测,均符合相关要求,表明该中药品种药物稳定性较好。
The formula of Nao De Sheng (NDS) which is composed of Panax notoginseng (Burk.) F.H.Chen, Radix Puerariae, Carthamus tinctorius L, Crataegus pinnatifida Bge. and Ligusticum Chuanxiong Hort. comes from Chinese Pharmacopoeia 2005(part one). The major effects of this medicine include reducing stasis and improving blood circulation, mediating main and collateral channels, and regaining consciousness. It is a remedy for cerebral arteriosclerosis, stoke and sequel of cerebral hemorrhage. It has a longer use time and leads to more accurate effects. The thesis adopt modern common character key technology to research the compound Naodesheng,including the extraction and purification process, preparation formulation reform,qulity standard,stability,etc,aim at providing bases of the secondary development about the Naodesheng preparation.
The method of solvent and the technology of macroporous adsorption resin purification were used to study the extraction and purification process about the main effective part of compound Naodesheng,optimize the best extraction and purification process,obtain the reliable technical parameters and proved by pilot test, these can make transition to industrialization; the total content of effective part in the extracts is over 50%,which is accord with relevant regulations of SFDA.
On the basis of the study on the extraction and purification process about the main effective part of compound Naodesheng, we did research into the preparation technology about the new formulation "Naodesheng soft capsule", determined the preparation of the contents, mixture and suspension of the drugs and excipients,the preparation of the capsule materials, compatibility of contents and rubber,etc, and proved by pilot test. The qualified rate of the soft capsule is 94.3%.
The modern analysis methods were carried out to study on the characters,TLC, gross deviation, disintegration and determination of the Naodesheng soft capsule systematically,set the perfect quality standard.
Adopted the accelerated test to study the preliminary stability about three batches samples in pilot test of the Naodesheng soft capsule in three months. According to the detection of each index in quality standard,the results are accord with relevant regulations .It shows that this herb species has a good stability.
采用溶剂法和大孔吸附树脂纯化技术,对脑得生复方中主要中药有效部位提取纯化工艺进行了研究,优选了最佳提取纯化工艺,取得了可靠的技术参数,进行了中试验证,可过渡到产业化;其提取物有效成分的总含量达到50%以上,符合国家食品药品监督管理局的相关规定。
在复方脑得生中药有效部位提取纯化工艺研究的基础上,对该复方的新剂型“脑得生软胶囊”的制剂工艺进行了研究,确定了囊芯液的制备、药物与辅料混悬、囊材制备、内容物与胶皮的相容性等技术参数,并进行了中试放大验证。其软胶囊成品合格率达94.3%。
采用现代分析方法,对脑得生软胶囊的性状、薄层鉴别、装量差异、崩解时限、含量测定等进行了系统研究,制订了该中药制剂较完善的质量标准。
采用加速试验的方法,对脑得生软胶囊的三批中试样品进行三个月的药物初步稳定性考察,按本品质量标准各项指标检测,均符合相关要求,表明该中药品种药物稳定性较好。
The formula of Nao De Sheng (NDS) which is composed of Panax notoginseng (Burk.) F.H.Chen, Radix Puerariae, Carthamus tinctorius L, Crataegus pinnatifida Bge. and Ligusticum Chuanxiong Hort. comes from Chinese Pharmacopoeia 2005(part one). The major effects of this medicine include reducing stasis and improving blood circulation, mediating main and collateral channels, and regaining consciousness. It is a remedy for cerebral arteriosclerosis, stoke and sequel of cerebral hemorrhage. It has a longer use time and leads to more accurate effects. The thesis adopt modern common character key technology to research the compound Naodesheng,including the extraction and purification process, preparation formulation reform,qulity standard,stability,etc,aim at providing bases of the secondary development about the Naodesheng preparation.
The method of solvent and the technology of macroporous adsorption resin purification were used to study the extraction and purification process about the main effective part of compound Naodesheng,optimize the best extraction and purification process,obtain the reliable technical parameters and proved by pilot test, these can make transition to industrialization; the total content of effective part in the extracts is over 50%,which is accord with relevant regulations of SFDA.
On the basis of the study on the extraction and purification process about the main effective part of compound Naodesheng, we did research into the preparation technology about the new formulation "Naodesheng soft capsule", determined the preparation of the contents, mixture and suspension of the drugs and excipients,the preparation of the capsule materials, compatibility of contents and rubber,etc, and proved by pilot test. The qualified rate of the soft capsule is 94.3%.
The modern analysis methods were carried out to study on the characters,TLC, gross deviation, disintegration and determination of the Naodesheng soft capsule systematically,set the perfect quality standard.
Adopted the accelerated test to study the preliminary stability about three batches samples in pilot test of the Naodesheng soft capsule in three months. According to the detection of each index in quality standard,the results are accord with relevant regulations .It shows that this herb species has a good stability.
引文
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[2]鲍建才,刘刚,丛登立,等.三七的化学成分研究进展[J].中成药,2006,28(2):246-153
[3]杨志刚,陈阿琴,俞颂东.三七药理研究新进展[J].上海中医药杂志,2005,39(4):59-62
[4]中国药典委员会.中国药典,Ⅰ部[S].北京:化学工业出版社,2005:233
[5]Kinjo J,et al.Chem Pharm Bull,1987,35(12):4846
[6]Nohara T,Kinjo J,Furuusanwa J,et al.But -2-enolides from Pueraria loba
[7]Kinjo J,Miyamoto I,Murakami K,et al.OIeanene- sapogenols from Puerariae radix[J].Chem Pharm Bull,1985,33(3):1293
[8]Takahashi Y,Miyassaka N,Tasaka SH,et al.Constitution of two coloting matters in the flower petals of carthamus tinctorius L[J].Tetrahedron Lett,1982,23(49):5163-5164
[10]Takahashi Y,Satio K,Yanagiya,et al.Chemical constitution of safflor yellow B,a quinochalcone C-glycoside from the flower petals of carthamus tinctorius L[J].Tetrahedron Lett,1984,25(23):2471-5172
[11]Meselhy M R,Kadota S,Momose Y,etal.Two new quinochalcone yellow pigments from Carthamus tinctorius and Ca2+ antagonistic activity of tinctormine[J].Chem Pharm Bull,1993,41(10):1796-1802.
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[13]Yin n B.et al.A novel semi-qulone chalcone sharing a pyrrol ring C-glycoside from Carthmus tinctorius[J].Tetrahedron Let,2000,41(12):1955-1958.
[14] M. N. Kim, E. Le Scao-Bogaert. Panta Med. 1992, 58,285-286.
[15] Masao Hattori,Xin-li,Huang,Qing-ming Che,Yukio Kawata, Yasuhiro T ezuka,Tohru Kikuchi. Phytochemistry,1992,31 (11),4001-4004.
[16] Li Yan-Mei,Che Qing-Ming. Acta Pharmaceutica Sinica. 1998,33(8), 626-628.
[17] Sadao Sakamura, Yoshihiko Terayama, Satomi Kawakatsu, Akitamilc hihara,Hideya Saito. Agr. Biol.Chem. 1980, 44(12), 2951-2954.
[18] Ken-ichi Ichihara,Manjiro Noda. Agr. Bio. Chera. 1975, 39(5), 1103-1108.
[19] Sadao Sakamura, Yoshihiko Terayama, Satomi Kawakatsu, Akitami Ichihara. Agr. Biol. Chem. 1978,42 (9), 1805-1806.
[20] Sadao Sakamura, Yoshihiko Terayama, Satomi Kawakatsu Akitami Ichihara. Agr. Biol. Chem. 1980, 44 (12), 2951-2954.
[21] HirojiSato,HirokazuKawacishi,TsutomuNishimura, ShinichiroKatduragi. Agr. Biol. Chem. 1985,49 (10), 2969-2974.
[22] Hui Li-Zhang,AkitoNagatsu,JinsakuSakakibara. Chem. Pharm. Bull. 1996,44 (4), 874-876.
[23] HuiLiZhang, AkitoNagatsu, ToshihiroWatanabe, JinsakuSakakibara. Chem. Pharm. Bull. 1997, 45 (12), 1910-1914.
[24] Rhoda Palter, R.E.Lundin, Glenn Fuller. Phtochemistry. 1972,11,2327-2328.
[25] AkitoNagatsu,HuiLiZhang,ToshihiroWatanabe,Nari Taniguchi. Chem. Pharm. Bull. 1998, 46 (6), 1044-1047.
[26] Rhoda Palter, R. E. Lundin. Phtochemistry. 1970, 9,2407.
[27] Rhoda Palter, R. E. Lundin. Phtochemistry. 1970, 9, 4298.
[28] Rhoda Palter, R. E. Lundin, W. F. Haddon. Phtochemistry. 1971,10,1587-1589
[29] RhodaPalter, R. E. Lundin. W. F. Haddon. Phtochemistry. 1972,11, 2871-2874
[30]Akito Nagatsu,Hui Li Zhang,Toshihiro Watanabe,Nari Taniguchi,Hajime Mizukami,Jinsaku Sakakibara.Chem.Pharm.Bull.1998,46(6)1044-1047.
[31]Toshihiro Akihisa,Hirotoshi Oinuma,Toshitake Tamura,Yoshimasa Kasahara.Phtochemistry1994,36(1),105-108.
[32]张培成,徐绥绪,郭虹.山楂果化学成分的研究[J].沈工学院学报,1999,13(2):87-89.
[33]董英杰,张乃先,张明磊,等.大果山楂叶黄酮成分研究[J].沈阳药科大学学报,1996,13(1):31-33.
[34]张培成,徐绥绪.山楂叶中两个新黄酮[J].沈阳化工学院学报,1999,13(3):236-237.
[35]中国人民解放军第一五七医院中草药研究组.山楂[J].中草药通讯,1975,5:46-55.
[36]许正斌,高奎斌,许双贵.山楂叶综述[J].中医药学报,1985,13(4):49-51.
[37]张培成,徐绥绪.山楂叶化学成分研究[J].药学学报,2001,36(10):754-757.
[38]英锡相,李绍维,林延会,等.山楂叶植物学及化学成分研究近况[J].辽宁中医学院学报,2001,3(2):98-99.
[39]张培成,徐绥绪.山楂叶中新黄酮化合物的分离与结构鉴定[J].中国药物化学杂志,1999,9(3):214-215,234.
[40]时岩鹏,丁杏苞.山楂化学成分的研究[J].中草药,2000,31(3),173-174.
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