The Compatibility Rule And Pharmacodynamic Action Foundation Of Zhu Yun Recipe Ⅲ

This study summed up the experimental and clinical platform of these tenyears. With orthogonal disassembled recipes, it further investigated thepreventive and therapeutic effects to spontaneous abortion, by affectingabortion animal models of corepus luteum inhibition due to renal deficiencywith Zhu Yun recipeâ…¢. Approached the contribution degree to the whole recipeand the optimizing dose matching of compound recipe invigorating the kidneyand compound recipe enhancing the spleen that compose Zhu Yun recipeâ…¢.Analyzed the relationships of important pharmacological compositions andmajor pharmacological results. Separated Zhu Yun recipeâ…¢into two chemicalsitus by water extract-ethanol precipitation. Made assaying according to thecharacteristics of chemical construction and traced pharmacologically theconcentration part of active substance. Make correlation analysis with indexesof every disassembled recipe in orthogonal experiment and substance contentin the recipes. Confirmed initially the active substance and the time phaseof its peak group.General condition of experimental and clinical study:empirical studies were made on holo-therapy of Zhu Yun recipeâ…¢to many linksof abortion. Carried out mainly on the influences of medicine to endocrinesecretion, immune tolerance, excitability of uterine smooth muscle, decidualcell fator, cytokine receptor and gene expression regulation, etc. Theanti-abortion mechanism of Zhu Yun recipeâ…¢is concerned with adustting theendocrine secretion function of the matrix, elevating the levels of hormonessuch as aquadio and corporin, increasing the expression of uterine caduca PRL-R,PR,ER, decreasing the excitability of excised uterus to repress uterinecontraction effect, elevating blocking antibody and so on. Correct the balanceexcursion of Th1, Th2 type cell factors of early fetation patients withthreatened abortion to make caduca Th1/Th2 balance deflect to Th2 type.Interfered in with deltamethrin to show the regulation effects of Zhu Yunrecipeâ…¢to cytokine receptor and Cx43 gene expression. Authenticatedabortion model repeatedly with multiple points of view. Made abortion modelsof corepus luteum inhibition with mifepristone (RU486), the abortion ratesachieved 83%. Made renal defficiency models of gestation period withribonucleotide reductase catastaltic hydroxycarbamide, the abortion rateswere 60%. Oxytocin-acupuncture models, the abortion rate was 93%. Establishedcorepus luteum inhibition models based on gestation period renal deficiencyand spleen deficiency models, and thereby made corepus luteum inhibitionmodels due to renal deficiency and corepus luteum inhibition models due tospleen deficiency. They were disease-syndrome combine models. Establishedspleen deficiency models of gestation period with apoplon, the abortion rateswere 53.85% Made renal defficiency models of gestation period withhydroxycarbamide, all of the abortion rates achieved 86%. By appraisement,those patent disease-syndrome combine models were in leading condition throughexterior and interior. These authentications with multiple points of viewindicated the procession and dependability of studies of Zhu Yun recipeâ…¢.It showed prevention and cure functions of Zhu Yun recipeâ…¢, to observe dosageform pharmacodynamics, therapeutic effect and safety evaluation frommultistrata clinically.Empirical methods and results:1. Methods of orthogonal disassembled recipes and results for Zhu Yun recipeâ…¢to the abortion rate of pregnant rats.Applied orthogonal design to make recipe disassembling study with Zhu Yunrecipeâ…¢, decided the affectois and level degree. Repeated the experimenttwice according to the design of orthogonality card L₉(3²). Observed theinfluence of Zhu Yun recipeâ…¢to abortion animal models of corepus luteuminhibition due to renal deficiency.The results of abortion inhibition ratio indicates that the recipeinvigorating the kidney contribute most to the whole recipe to elevating the inhibition ratio of rats abortion, while the recipe invigorating the spleenminor, which shows the recipe invigorating the kidney plays the major rolein the whole recipe to inhibit the abortion rate of abortion animals of corepusluteum inhibition due to renal deficiency, while the recipe invigorating thespleen plays a minor one. Both of the two recipes show obvious synergy.The results of pregnancy hormone level show that the contribution degreesof the recipe invigorating the kidney and the recipe invigorating the spleenare similar in elevating the pregnancy hormone level of abortion rats for thewhole recipe. That indicates both of the two recipes play major parts inelevating the pregnancy hormone level of abortion animals of corepus luteuminhibition due to renal deficiency.The results of dihydrofolliculin level indicate that the recipeinvigorating the kidney contributes most for the whole recipe to elevatingthe dihydrofolliculin level of abortion rats while the recipe invigoratingthe spleen minor. That shows the recipe invigorating the kidney plays the majorrole in the whole recipe to inhibit the dihydrofolliculin level of abortionanimals of corepus luteum inhibition due to renal deficiency, while the recipeinvigorating the spleen plays a minor one. Furthermore, the two recipes showobvious synergy.All of the results of abortion inhibition ratio, pregnancy hormone anddihydrofolliculin levels show that Zhu Yun recipeâ…¢reacts mainly byinvigorating the kidney while secondly by invigorating the spleen. That isCoincident with Dr. Luo's theory: the formation of a fetus lies mostly inthe congenital kidney-QI, while to support the fetus lies in QI and bloodgenerated by the postnatal spleen and stomach of the matrix. Therefore, renaldeficiency leading to not consolidating and spleen not providing are essentialfor the morbility of unstable fetal movement.The results of pathomorphological detection show the abortion rate ofmodel group is obviously higher than medication group. The abortion rate oflevelâ… in recipe 9 (recipe 1 to recipe 3) is comparatively high. It degradesin levelâ…¡(recipe 4 to recipe 6) and it's the lowest in levelâ…¢(recipe7 to recipe 9). The results is a little different to the abortion rates oforthogonal disassembled recipes. But the basic dose-effect relationships areapproximate. The results are just the same as those of orthogonal disassembledrecipes of pregnancy hormone and dihydrofolliculin. All of these indicate A3B3plays the most important part in preventing and curing abortion.To analyze synthetically abortion inhibition ratio, pregnancy hormone anddihydrofolliculin levels and make weighting for contribution degree. The results indicate that the recipe invigorating the kidney plays the major rolein the whole recipe while the recipe invigorating the spleen plays a minorone and that the two recipes show obvious synergy. That matches what Dr. Luopointed out, "once there are abortion premonitions for a fetus, it is badlyin need of invigorating the kidney and the spleen to consolidate the fetus",and the theory from , "toinvigorate the congenital renal and the postnatal spleen is just to consolidatethe Qi and blood of the fetus. Shouldn't invigorate both of the spleen andthe renal?!"2. Authentication methods and results of the confidence for orthogonalexperiment results of Zhu Yun recipeâ…¢Combines orthogonal design results and aggregate analysis and get anoptimizing recipe. Study the influences of the optimizing recipe and theoriginal recipe to abortion animal models of corepus luteum inhibition dueto renal deficiency, so as to authenticate the confidence for orthogonalexperiment results.The experiment results indicatethat both of the optimizing recipe andthe original recipe obviously inhibit animal abortion, elevate experimentanimal's pregnancy hormone level and dihydrofolliculin level. That shows theresults of orthogonal experiment are dependable.3. The chemical-situs separating and pharmacodynamic action tracing of ZhuYun recipeâ…¢Used alcohol to precipitate the extract from the optimizing recipe ofZhu Yun recipeâ…¢and made into alcoholic solution part and sediments part.Used abortion animal models of corepus luteum inhibition due to renaldeficiency to trace the pharmacodynamic action of the active substance of thecomplex prescription, so as to Confirm the concentrate situs of the activesubstance of Zhu Yun recipeâ…¢.Experimental results indicate that both of alcoholic solution part andsediments part, precipitated out of the water extract from the optimizingrecipe of Zhu Yun recipeâ…¢, obviously inhibit the abortion ratio of abortionanimal models of corepus luteum inhibition due to renal deficiency, elevateabortion animal's pregnancy hormone level and dihydrofolliculin level. Thatshows both of two parts are the concentrate situs of the active substance.4. Apply correlation analysis to decide the active substance of Zhu Yun recipe â…¢initiallyMethod: alcoholic solution part: the water extract out of the 9 disassembledrecipes by orthogonal design, after being disposaled with macroporous resin,applied liquid phase sample introduction, used gradient elution to determinethe peak area of the sample introduction substance, made correlation analysiswith pharmacodynamic indexes of orthogonal design. Sediments part: conditionlimited, applied official method to determine the polysaccharide content andmake correlation analysis with pharmacodynamic indexes of orthogonal design.Results: the results of correlation degree analysis indicate: the correlationdegree of the time peaks of 2.93min, 3.75min, 14.79min, 27.48min, 35.35min,45.5min, 56.33min, 89.90min, 94.43min, 112.1min, 134.89min and thepolysaccharide are higher than 0.7. They may be the active substance for ZhuYun recipeâ…¢to inhibit abortion rat models suffering corepus luteuminhibition disease.5. Indirect authentication of the correlation analysis results of Zhu Yunrecipeâ…¢Method: apply abortion animal models of corepus luteum inhibition due to renaldeficiency to authenticate the pharmacodynamic action of the active substanceconcentration part and the remaining substance part of the optimizing recipeof Zhu Yun recipeâ…¢, so as to authenticate the confidence of correlationanalysis result.Results: the experiment results indicate that the concentration part of theactive substance inhibits the abortion rate of model'animals obviously, whilethe remaining substance appears to be weaker. The results authenticate to someextant that the method of finding the active substance of a complexprescription through correlation analysis is feasible and dependable.Conclusions: This study successfully applies orthogonal design to studythe compatibility rules of the two compound compositions of Zhu Yun recipeâ…¢, recipe invigorating the kidney and recipe invigorating the spleen. Theexperiment results indicate that the two compound compositions interact eachother in numerous indexes of abortion animal models of corepus luteuminhibition. Orthogonal experiment results show some sense of instruction forthe clinical compatibility use and dosage handling of Zhu Yun recipeâ…¢. Still,this study successfully applies mathematics method of correlation analysisto find the active substance of Zhu Yun recipeâ…¢, confirms the concentrationsite and structure of the active substance initially and simultaneously authenticates the feasibility and dependability of the correlation analysisresults with abortion animal models of corepus luteum inhibition due to renaldeficiency. That makes an infarctate study platform and essential evidencefor separating the active substance further, determining the structure of theactive substance, enacting quality specification and being developed intoChinese patent medicines. At the same time, through researching, this studyshows Zhu Yun recipeâ…¢degrades the abortion rate of corepus luteuminhibiting animal due to renal deficiency through multicomponent effectingmultitarget.