| Objective:To make a preliminary evaluation on the quality of ?-Asarone in-situ-gel; Investigate absorption after a-Asarone in-situ-gel, Blank in-situ-gel and catgut implantation; Study effective mechanism of ?-Asarone in-situ-gel in the treatment of asthma and investigate its pharmacokinetic behavior in rabbit body by further research.Methods:Through the investigation of the properties of ?-Asarone in-situ-gel, establishing a preliminary evaluation of the preparation; Blank in-situ-gel, ?-Asarone in-situ-gel and catgut are implanted in each group,studying in seven periods(15d, 20d,25d,30d,35d,38d,40d) implant site changes of granuloma area and striated muscle area ratio and comparing the absorption; Using ovalbumin induced rat asthma model,investigating intervention ?-Asarone in-situ-gel, blank in-situ-gel and catgut in rats with asthma, observing the pathology slice and counting of inflammatory cells, using ELISA method and immunohistochemical method to determine the expression of related factors, explore the mechanism of ?-Asarone in-situ-gel in the treatment of asthma; To establish a method for determination of ?-Asarone in rabbit plasma with UPLC/UPLC-MS, investigate rabbits blood drug concentration of ?-Asarone in-situ-gel after different time, and analysis data.Results:The preparation is colorless and transparent gel, better formability and cured through needle resistance, pH value is appropriate; Catgut induced granulomas and striated area ratio less than the other two groups, but the fastest absorption is blank in-situ-gel after ?-Asarone in-situ-gel? blank in-situ-gel and catgut; Ovalbumin induced asthma rat experiment show that ?-Asarone in-situ-gel showed better therapeutic effect; Its mechanism may be related to reduce inflammatory cells infiltration, the immunoglobulin E, rats ovalbumin specific IgE, interleukin 4 (IL-4) content, increase interferon y(IFN-?) content, regulate Th1/Th2 proportion, and inhibit transforming growth factor ?1 (TGF-?1) protein expression and bronchial lung tissue of matrix metalloproteinases (MMP-9) and release of the expression of leukotriene B4 and C4; after ?-Asarone in-situ-gel embedding acupoint in rabbit, the average plasma concentration-time curve fitted to the non-compartment model, after 20d determine a-Asarone in rabbit plasma, has a good sustained-release effect.Conclusion:The paper preliminarily evaluate the quality of a-Asarone in-situ-gel preparations; Granuloma experimental results show that a-Asarone in-situ-gel absorption rate is lower than the rest of the two groups, the reason still need further study, but found that after implantation of a-Asarone in-situ-gel stimulation to the tissue in the 25d reached the maximum value, a-Asarone in-situ-gel in the treatment of bronchial asthma caused by ovalbumin has obvious effect, it can provide reference for clinical medication; Method for determination of a-Asarone content in rabbit plasma is simple and reliable and has strong specificity, high sensitivity and good reproducibility of the characteristics, the results of its pharmacokinetics showed that the preparations of implant acupuncture point has good sustained-release behavior. |
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