定位—定时多元释药

【作者】 薛钰；

【导师】 李小芳；

【作者基本信息】 成都中医药大学 ， 药剂学， 2008， 硕士

【摘要】 本课题针对溃疡性结肠炎(UC),从现代中药复方释药系统角度出发,以综合疗效发挥为核心,以中医药理论为基础和以新型释药系统理论为手段。根据中西医对UC的病机和治疗原则的分析,以治疗UC有效的结肠康方中黄芪和苦参的提取物为基础,将黄芪中的皂苷、多糖制成胃内吸收,起全身免疫调节作用,苦参中的苦参碱、氧化苦参碱制成结肠定位释药系统,起局部消炎、抗菌作用,体现了中医治疗UC的标本兼治、整体与局部相结合的治疗法则。口服结肠靶向给药系统(Oral Colon Targeting Drug-delivery System,OCTDS)是通过药物传递技术,使药物口服后,在上消化道不释放,将药物运送到人体回盲部后开始崩解或蚀解并释放出来,从而能够使药物定位于人体结肠后,在结肠部位发挥局部或全身治疗作用。通过对OCTDS释药机理的分析,分别对pH-时滞依赖型和pH-酶依赖型两种联合给药制剂及其评价进行了研究,研制出具有较好结肠定位释药的靶向制剂。主要研究内容如下:根据药物性质,对半成品进行了性状、TLC鉴别、含量测定等项目的研究,并对相关物质进行了检查,通过对半成品定性、定量方法的考察,建立了半成品的质量标准。将黄芪和苦参提取物分别制成微丸,通过试验筛选,确定了素丸的制备工艺。对pH-时滞依赖型和pH-酶依赖型两种联合给药系统进行研究,分别筛选出合适的靶向包衣辅料,并确定包衣工艺,将微丸分装胶囊。通过体外释放度试验,研究并建立了制剂体外释放度测定方法,采用硫酸钡造影技术对pH-时滞依赖型和pH-酶依赖型结肠靶向制剂的体内释放性能进行了考察,结果表明,该制剂在正常人体内基本达到结肠定位释放的效果。对制剂建立了TLC定性鉴别方法,运用高效液相法对制剂进行了含量测定,拟订了制剂中苦参碱、氧化苦参碱的含量要求,建立了制剂的质量标准。更多还原

【Abstract】 The topic for ulcerative colitis （UC）, from the perspective of compound release system of modern Chinese medicine ,the effect of an integrated plays as the core and Chinese medicine based on the theory and the new release system theory as a means of. According to Western medicine in the pathogenesis of UC principles of analysis and treatment, based on the extract of Kushen and Huangqi which effective to UC treation. Astragalus will be the saponin, gastric absorption into polysaccharide, and Systemic immune from regulation. Kushen of matrine, oxymatrine made of colon-release system, from the local anti-inflammatory, antibacterial activity. UC embodies the Chinese medicine treatment of tackling both the symptoms, and overall treatment of a combination of local rules.The technique of drug transfer is used in Oral Colon-targeting Drug Delivery System （OCDDS）, in which drugs does not release in the upper digestive tract with oral administration but begins to collapse or erode when they arrive at ileocecus and act medicinally at colon. Aiming at Ulcerative Colitis （UC）,we researched on Jiechangkang, which is an efective cure for UC in clinical use. We design a binary release programme, making it in the stomach and colon, respectively release to going to play the effect. By OCDDS release mechanism analysis,we have got two colonic targeting preparations after research: PH-time lagged relying and pH-enzyme relying delivery systems. The main contents include:By studying the medical materia character、TLC and assaying ,build up the qualitation and quantitation of half-finished product. The Jiechangkang extraction is prepared into micro-pills,aftert he screen-out experiments on preparing process. The PH-time lagged relying and pH-enzyme relying delivery system shave beens tudied.B oth coating excipients of micro-pills and the coating process have also been decided.Coating micro-pills are capsuled afterward. By established a method of in vitro dissolution determination for preparations. Reviewed the PH-time lagged relying and pH-enzyme relying colon aration in vivo release by BaSO₄ photographytechnology ,as a result,it could achieve the objective of colon oriented releasem a normal human body.Build TLC to examine the relative substances and apply the HPLC to assay content, formulated the content limits of matrine and oxymatrine inpreparation ,define the quantitation standard.更多还原