防潮辅料在中药固体制剂中的应用研究
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摘要
中药固体制剂是现代中药制剂的主要形式,而经过提取分离制成的中药全浸膏固体制剂皆具有不同程度的吸潮性,吸潮后导致中药制剂外观颜色变深、结块、变软、流动性降低、甚至霉变,从而影响药品的质量和疗效,给生产和储存带来困难。因此,中药制剂的吸潮问题一直是制药工作中较为普遍的难题。在实际生产中,因制剂的提取和精制工艺不便改动,通常以筛选辅料的种类和用量来降低制剂的吸湿性。本论文从辅料防潮入手,以有效组分防潮为研究对象,探索其在吸湿中药中应用的适宜性。
前期实验提取了黄芪、柴胡、人参中的多糖和皂苷组分,分别比较三者多糖和皂苷的吸湿性,发现多糖较皂苷易吸湿,并且以黄芪多糖吸湿最为严重,故选择黄芪多糖为本实验组分防潮的研究对象。
结合相关文献和以往实验经验,选择了常用的14种辅料进行了防潮性能的考察。将纯辅料及其与黄芪多糖混合的粉末在相对湿度为75%的条件下,25℃放置7天,绘制吸湿曲线,提取吸湿特征参数,初步筛选较优的辅料,并确定药辅比,结果乳糖、β-CD、CaHPO4、甘露醇、MCC5五种辅料与药物1：1配比较好。借助实验设计软件Design Expert,结合药物吸湿性和外观性的评价指标,运用混料设计法优选防潮辅料的种类及最佳配方,软件优选出了11组较优配比,以乳糖：MCC:CaHPO4=0.297:0.503:0.200为最佳。
筛选出糊精为普通颗粒的成型辅料。将有效组分筛选出的防潮辅料应用于单味药黄芪和复方当归补血方剂中,制成颗粒,以吸湿率、成型性、外观性状为指标,对其工艺进行适当地调整,筛选出较优配比的防潮辅料。考察普通颗粒与防潮颗粒、不同配方粉末、不同制备方法的吸湿特性。实验结果表明,与加入的普通辅料相比,加入了防潮辅料的药物可以有效降低其吸湿性,外观性状良好,总结了以有效组分筛选出的防潮辅料在单味药和复方制剂中的适宜性。
对当归补血方剂中间体及其颗粒进行了性状、薄层鉴别、含量测定等项目的研究,建立了质量标准。
Traditional Chinese solid preparations are the main form of modern Chinese medicine preparations. Traditional Chinese medicine (TCM) pure extract preparations of extraction and separation exist easy moisture absorption. The moisture absorption results in the solid drugs soften, the change of chemical composition and mold, which affects the quality and effect of drugs and brings difficulties to the production and storage. The moisture absorption has always been a general difficulty. In the actual production, for extraction and refining process of preparation change inconveniently,it is particularly important to screen the kinds and amount of the excipients for reducing hygroscopicity.This thesis focused on moisture-proof excipients. Effective component was choosed as a model drug to explore the suitability of hygroscopic TCM.
In early experiments, hygroscopicity of polysaccharides and saponins from astragalus, bupleurum, ginseng were compared respectively.The result was that polysaccharides were more hygroscopic than saponins. Astragalus polysaccharide (APS) which was the most serious hygroscopicity was selected as a model drug.
By consulting related literature and previous experimental experiece, this thesis investigated the moisture-proof function of 14 kinds of excipients. Pure excipients and the powders mixed with APS were at 75% relative humidity and 25℃for 7 days,to measure relative humidity of every mixture, then draw the moisture absorption curve and extract characteristic parameters.Preliminarily screen excipients and determine ratio between drug and excipients. The result was lactose,β-CD, CaHPO4, mannitol, MCC by 1:1 ratio with APS. Adopting mixture design with Design Expert optimized the most excellent combination of excipients. There were the better ratio of 11 groups.The best one was lactose, MCC and CaHPO4 by 0.297:0.503:0.200 ratio.
Forming excipient of ordinary granule was dextrin. The moisture-proof excipients of effective component were applied to astragalus and Dangguibuxue prescription which were made of granules. Adjustment process was for the appropriate moisture-proof excipients by hygroscopicity, formability and appearance. Moisture absorption characteristics of ordinary granule, moisture-proof granule,the powers of different formula and different preparation. The result showed that drug added moisture-proof excipients could effectively reduce the moisture absorption and improve the appearance, compared with drug added ordinary excipients. The thesis summarized the suitability of Single herb and TCM preparation adopting effective component's moisture-proof excipients.
前期实验提取了黄芪、柴胡、人参中的多糖和皂苷组分,分别比较三者多糖和皂苷的吸湿性,发现多糖较皂苷易吸湿,并且以黄芪多糖吸湿最为严重,故选择黄芪多糖为本实验组分防潮的研究对象。
结合相关文献和以往实验经验,选择了常用的14种辅料进行了防潮性能的考察。将纯辅料及其与黄芪多糖混合的粉末在相对湿度为75%的条件下,25℃放置7天,绘制吸湿曲线,提取吸湿特征参数,初步筛选较优的辅料,并确定药辅比,结果乳糖、β-CD、CaHPO4、甘露醇、MCC5五种辅料与药物1：1配比较好。借助实验设计软件Design Expert,结合药物吸湿性和外观性的评价指标,运用混料设计法优选防潮辅料的种类及最佳配方,软件优选出了11组较优配比,以乳糖：MCC:CaHPO4=0.297:0.503:0.200为最佳。
筛选出糊精为普通颗粒的成型辅料。将有效组分筛选出的防潮辅料应用于单味药黄芪和复方当归补血方剂中,制成颗粒,以吸湿率、成型性、外观性状为指标,对其工艺进行适当地调整,筛选出较优配比的防潮辅料。考察普通颗粒与防潮颗粒、不同配方粉末、不同制备方法的吸湿特性。实验结果表明,与加入的普通辅料相比,加入了防潮辅料的药物可以有效降低其吸湿性,外观性状良好,总结了以有效组分筛选出的防潮辅料在单味药和复方制剂中的适宜性。
对当归补血方剂中间体及其颗粒进行了性状、薄层鉴别、含量测定等项目的研究,建立了质量标准。
Traditional Chinese solid preparations are the main form of modern Chinese medicine preparations. Traditional Chinese medicine (TCM) pure extract preparations of extraction and separation exist easy moisture absorption. The moisture absorption results in the solid drugs soften, the change of chemical composition and mold, which affects the quality and effect of drugs and brings difficulties to the production and storage. The moisture absorption has always been a general difficulty. In the actual production, for extraction and refining process of preparation change inconveniently,it is particularly important to screen the kinds and amount of the excipients for reducing hygroscopicity.This thesis focused on moisture-proof excipients. Effective component was choosed as a model drug to explore the suitability of hygroscopic TCM.
In early experiments, hygroscopicity of polysaccharides and saponins from astragalus, bupleurum, ginseng were compared respectively.The result was that polysaccharides were more hygroscopic than saponins. Astragalus polysaccharide (APS) which was the most serious hygroscopicity was selected as a model drug.
By consulting related literature and previous experimental experiece, this thesis investigated the moisture-proof function of 14 kinds of excipients. Pure excipients and the powders mixed with APS were at 75% relative humidity and 25℃for 7 days,to measure relative humidity of every mixture, then draw the moisture absorption curve and extract characteristic parameters.Preliminarily screen excipients and determine ratio between drug and excipients. The result was lactose,β-CD, CaHPO4, mannitol, MCC by 1:1 ratio with APS. Adopting mixture design with Design Expert optimized the most excellent combination of excipients. There were the better ratio of 11 groups.The best one was lactose, MCC and CaHPO4 by 0.297:0.503:0.200 ratio.
Forming excipient of ordinary granule was dextrin. The moisture-proof excipients of effective component were applied to astragalus and Dangguibuxue prescription which were made of granules. Adjustment process was for the appropriate moisture-proof excipients by hygroscopicity, formability and appearance. Moisture absorption characteristics of ordinary granule, moisture-proof granule,the powers of different formula and different preparation. The result showed that drug added moisture-proof excipients could effectively reduce the moisture absorption and improve the appearance, compared with drug added ordinary excipients. The thesis summarized the suitability of Single herb and TCM preparation adopting effective component's moisture-proof excipients.
引文
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[1]蒋且英,廖正根,赵国巍,等.吸湿原理及中药制剂防潮方法研究概况[J].中国药房,2007,18(33)：2626-2628.
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[4]蒋且英,廖正根,赵国巍,等.吸湿原理及中药制剂防潮方法研究概况[J].中国药房,2007,18(33)：2626-2628.
[5]Serajuddin ATM, Thakur AB, Ghoshal RN, et al.Selection of solid dosage from composition through drug-excipient compatibility testing[J].Pharm Sci,2000, 88(7):696.
[6]孙淑萍,狄留庆,黄耀洲,等.中药全浸膏制剂防潮技术应用研究进展[J].时珍国医国药,2006,17(3)：342-343.
[7]冯翰,张晓冬,冯伟.三种不同配方的辅的影响[J].黑龙江医药,2002,15(4)：279.
[8]李智,韩静,李成顺,等.甘草浸膏吸湿性的研究[J].中药材2007,30(2)：223.225.
[9]王地,贾富霞,高燕,等.调肝颗粒剂成型工艺的研究[J].北京中医杂志,2003,22(5)：54.
[10]杨立华.康复肾胶囊中浸膏颗粒制剂工艺研究.中华实用中西医杂志,2005,18(13)：295-296.
[11]周静华.多糖的研究和临床应用前景[J].大理学院学报,2006,5(6)：72-74.
[12]张钰.中药多糖临床应用研究进展[J].甘肃医药,2008,27(4)：31-33.
[13]孙麒,巨勇,赵玉芬.具有生物活性的甾体皂苷[J].中草药,2002,33(3)：276-280.
[14]冯国宣.抗癌植物资源与天然产物研究[J].湖北民族学院学报(自然科学 版),2001,19(3)：26-32.
[15]霍文,孙广利,刘鹏.正交试验法优选茯苓多糖提取工艺[J].西北药学杂志,2006,21(2)：18-20.
[16]孙瑞敏,刘冬平,陈俊.黄芪多糖的提取[J].南开大学学报(自然科学版)2005,38(1)：33-36.
[17]陈芳艳,梁永彬,王林川.黄芪多糖提取方法的研究[J].广东畜牧兽医科技,2004,29(5)：37-39.
[18]薛亮,郭茂娟,范英昌.当归补血汤立法理论及配伍应用的探析[J].天津中医药,2010,27(1)：28-29.
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