Pharmaceutical And Pharmacokinetic Research On Kangshuansu

1. Purpose:Kangshuansu(ISA) is the synthetic compound of shikimene. It'spharmacological research results show that it has the functions ofanti-thrombosis and can improve the damage caused by cerebral ischemia.These functions revealed that Kangshuansu(ISA) has good prospect ofapplication and worth to study more. The basic chemical and physicalproperties, preparing technology, quality standards, stability andpharmacokinetic about Kangshuansu(ISA) and it's tablet were studiedsystemically in this thesis. From the results, we can analysis andevaluate Kangshuansu(ISA) and it's tablet precisely andcomprehensively.2. Methods:Different methods are used in this research, they are:(1) Basic properties of Kangshuansu(ISA): according to the pharmacopoeiaof the pepole's republic of China(2000), the solubility, water content,total ash, residue of ignition, heavy metals, arsenic are studied;Accelerated test were used at the research of Kangshuansu(ISA) at highlight, high humidity and high temperature.(2) Pharmaceutical technology: orthogonal design method was used toanalysis the effects on the tablet preparation. The best technologyparameters were determined.(3) The quality standard of Kangshuansu(ISA) tablet and sustained releasetablet: UV and TLC were used to identify Kangshuansu(ISA) tablet andsustained release tablet; Assaying method was HPLC, the quality standardwas established.(4) Stability test: Quarantine period method and accelerated test wereused to detect the stability of Kangshuansu(ISA) tablet and sustainedrelease tablet.(5) Pharmacokinetics experiment: HPLC was used to establish the analysismethod of Kangshuansu(ISA) in the plasma of beagle dog. DAS software wasused to analysis the result. Through the result of concentration to time,the pharmacokinetics parameters were got.3. Results:X(1) the basic properties of Kangshuansu(ISA): the solubility, watercontent , total ash, residue of ignition, heavy metals, arsenic arestudied; the stability and CRH were determined. Kangshuansu(ISA) isstable under the temperature of 40℃,60℃,80℃; but when put it underthe temperature of 90℃ for 8 days, the content was lost seriously.(2)the study on preparation of Kangshuansu(ISA) tablet and sustainedrelease tablet: the methods of granulation, the property of the granulate,the dosage of the excipients were selected by using the release degreeof Kangshuansu(ISA) in the tablets and the quality of the tablets as theindicators. The ratio of the excipients and the best technic parametersare established. Three batches of middle-scale products were manufacturedunder these technic parameters. After determination of these bathesproductions, we found that: the technic parameters were stable and thetablets were qualified.(3) the quality standard of Kangshuansu(ISA) tablet and sustained releasetablet were established.The Kangshuansu(ISA) in tablet was identified by using UV and ILC. Thecontent of Kangshuansu(ISA) tablet and sustained release tablet weredetermined by using HPLC and the content limit was established. Theresults showed that the negative sample didn't interfere with the sampledetermination. Identification and content determination methods arestable, specific and repeatable. The sustained release tablet releasetest methods and result were established. The release degree is 20～40%for 2hr, 40～60% for 8hr,not low than 70% for 16hr.(4) the stability study of Kangshuansu(ISA) tablet and sustained releasetablet: Use the established quality standard as the methods to detect thechanges of Kangshuansu(ISA)tablet and sustained release tablet. Theresults are: the samples are stable during the testing period of 12 months(at the room temperature).The Kangshuansu(ISA) tablet was stable underthe temperature of 40℃,60℃ ; but when put it under the temperatureof 90℃ for 7 days or over 7 days at 80℃,the content was lost seriously.Sustained release tablet was stable under the temperature of 4...