| Fertility Promoting Intrauterine Infusion Liquid (FPL) is a new kind of infertility drugs to prevention and treatment of dam inactive ovary and lasting corpus luteum, and its preparations by motherwort, Epimedium andsafflowerby method of waterextraction and alcohol precipitation.The main function of FPL is kidney impotence, blood circulation, promoting the pregnant aphrodisiac, which is deeply focused by theveterinary clinic. However, due to the easily leakage after pouring the FPL into damuterus, which influences the effect of treatment, and a higher frequency of dosing, increasingirritationofdams, damsuteruscould easily lead tomechanical damage.In situ gel is a verypromisingnew drug deliverysystems, and it has beenwidely usedinvariousclinicalskin, eyes, nose, mouth, vagina, rectum, etc. the route of administrationto control the drug release. Poloxamerwas a kind of matrix material for preparing temperature-sensitivein situ gel and ithas been widelyusedDrug Carriers Study.In this experiment,FPLas a modelChinese herbal compoundand preparationin situ gelfortraditional Chinese medicine, in vitro release, in vitro dissolution, In vivopharmacodynamic properties were inspected. In this experiment.we hope to prepare Fertility-promoting Intrauterine Infusion in situ Gel (FPG) foruterineperfusion successfully, and the clinical application deficiency of leakage and high frequency of administration were improved, thebioavailability andefficacy of drugs was increased.In vitroanalysis oficariinand totalflavonoids were established, obtainingthe regression equation of concentration and peak area of icariin:S=43690.18C+16581.14(R2=0.9997), the regression equation of total flavonoidsconcentration and absorbance: A=0.0246C+0.0174(R2=0.9993).In order toinvestigatethepreparationof FPL of various factorsonthe efficiencyofextraction, icariin and flavonoids were appointed asindicators. The extraction parameterswas optimized by using response surface central composite design on the basis of single factor experiment. The experiment results showed that, liquid ratio, boiling time, extraction times, the threefactorshave a more significantinfluenceon extractionrate of icariinand totalflavonoids in progestationalperfusion, and have a less effecton the extraction rateofimmersion time. The optimumextraction process ofresponse surface methodologywasobtainedafteroptimization:extraction time was 10 min.liquid ratiowas17.5 mL/g.extraction time was38 min.extractedfor 3 times. Quadraticpolynomial regressionmodelswere obtainedextraction rate of icariinandtotal flavonoidsofliquid ratio(A).boiling time(B), extraction times(C) inprogestationalperfusion is:extraction rate of icariin(mg/g)=2.23+0.097 A+0.037 B+0.021 C+4.445><10-3 AB+0.14 AC+0.14 BC-0.17 A2-0.10 B2-0.37 C2. Extraction rate of total flavonoids (mg/g)= 14.11+0.16 A+0.27 B+0.60 C+0.21 AB+0.056 AC+0.099 BC-0.55 A2-0.36 B2-0.66 C2.Investigate the effect ofpoloxamer407, poloxamerl88, HPMC, sodium alginate, etc. forgellingtemperature. The resultsshowed that the content of poloxamer 407and poloxamer188has a significant influenceonthe gellingtemperature. and the impact of HPMC andsodium alginate on gelation temperatureis not obvious. Alsoadding FPL to theblankgelwillsignificantly reducethe gelation temperature.According topreliminaryresults,ratio ofl8%P407+5.0% P188+0.3%SA+FPL,18% P407+7.5% PI 88+0.3%HPMC+FPLand19%P407+2.5% P188+0.3% HPMC+FPLgeltemperatures were(29.3±0.3), (27.9±0.2)and(27.3±0.4)℃, it is more appropriate. Takethese threesitu gelformulationsfor in vitrodissolutionand in vitrorelease test. The results showed thatthree kinds ofin situ gelduringS h, FPGdissolutionrate and thedrug releasingrate reachedabout 90%, which have no significant difference. Respectively5the cumulativereleaserate oftliree kinds ofgel(η)cumulativedissolutionrate(X)mapping,the regressionequations were η=0.9282X-0.0012 (R2=0.9915),η=0.9806T-0.0331 (R2=0.9936), η=1.0021X-0.0183 (R2=0.9978), good linear relationship, and the slope ofthe fitting equationis close to 1, indicating that the geldissolutionis the main factor ofcontrollingthe drug release.Sol-gelquickly convertsinto solidgelafterFPG was ingected into the Subcutaneous ofrat, indicating that theFPGhas a goodgelling characteristics invivo, meeting the expecting and clinical requirements. Studythe impactofFPLandFPG on uterusand ovarieslndex.Research the organizationsandslicing of ratuterus, and observe the effects ofFPLandFPGon endometrial. The resultsshowed that, FPL andFPGcanincrease index of uterineand ovarian of rats, however, effect of FPG significantly is better. FPLandFPGhadno significanttissue damage to endometrium.The serumestradiollevelsas an indicatorto studythe impactofFPLandFPG on levels ofserumestradiol. The results showed that, FPL andFPGincontinuous administrationfor 7 days,serumestradiollevelsincreased significantly.andestradiol levelsFPGratsissignificantly higher than theFPL,with a further increaseof administrationtime, FPG groupestradiol levels inratsgradually decreased, and finally atFPLflat,butwere significantlyhigher than the previousadministration,serumestradiollevels. Experiments showed thattheFPL was prepared to be FPG, which can slow release ofthe drug and mayhave a betterefficacy.Conduct low temperature test, high temperature test and glare test after the preparation of FPG with ampoule potting.The resultsshowed that. FPG arestableat conditions of low temperature, high temperature and stronglight.Experimentssuccessfully preparedFPG,this methodis simple,reliable, and controllable quality. DrugQuality Assessment, in vitrorelease experimentsand pharmacodynamicexperiments showed, compared withFPL, FPG hasthe characteristics of slowrelease. which can reduce the number of drugs, and have good prospects forthe developmentand clinicalapplication value. |
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