Development Of A Compound Medicine Of Anti-osteoporosis Durgs And Releative Study On It's Pharmacological Effacicy

1 ObjectiveDevelop a new kind of medicine for treatment of postmenstruation osteoporosis,which,are made of calcium carbonate,vitamine D₃,soybean isoflavone, alendronate sodium et al..the pharmacy efficacy for each elements and the compound medicine are tested based on an ovariectomied osteoporosis animal model experiment.2 Methods2.1 Preparation of the compound medicine with mutiple ingredients.The new medicine for treatment of postmenstruation osteoporsis with 4 active ingrediments are produced with model-compression method.Then the contents of the calcium carbonate,vitamine D₃,soybean isoflavone were checked with HPLC(high performance liquid chromatograph),while the alendronate sodium was examinated with spectrophotometer,and the product's rigidity,brittleness and break-down ablility and qulity uniformity were tested to control the qulitly of the compound medicine for fiting the clinical use standard..2.2 An study on the pharmacy efficacy of the anti-osteoporosis compound medicine40 grown up female SD mice were divided into 5 groups randomly:ovariectomy with calcium carbonate plus vitamine D₃,(group A),ovariectomy with calcium carbonate plus vitamine D₃,and isoflavone(group B),ovariectomy with calcium carbonate plus vitamine D₃ and isoflavone and alendronate sodium(group C),sham operated group and model group(ovariectomied).All mice take in medicines 3 weeks after the operation and were fed in the cage for 2 months and were killed.Then the procedure as follow were done:â‘ The chemical parameters as:Ca,ALP in the serum were checked respectively;â‘¡The urterus were taken out and wash clean by deonion water,absorbed up the water and weigthed in,then the organ index were calculated on formula,â‘¢The hummerla bone were taken out to check the weigth of wet and dry bone,the length and width of the bone,the content of mineral.â‘£the right femural bone were taken out to check the rupture strength in the bimechanical instrument.⑤The left femural bone were taken off to test the bone material density;the right femural bone were stabilized,decalcificated,inbeded, made into slices and dyed with HE to observe the microstucture of the bone trebecula.and the effacicy for different ingrediments of the compound medicine were analysed for treatment the osteoporosis.2.3 The statistical analysisThe statistical analysis in this thesis were processed with SPSS software.One-way ANOVA followed by least significant different test.(or Dunnett's T3 test,if equal variances not assumed)3 Result3.1 Preparation of the tabletThe compound tablet with 4 efficacy ingredients were prepared with compression method.The soybean isoflavones,anlendronate sodium,calcium,vitamine D₃ were mixed up and screened,then added with adhensive material and were compressed into tablets in the rotateing molde mathine.The whole process were under standard procedures.in the last step,the quality and active ingredient content examination result show that the content of the calcium carbonate,vitamine D₃,soybean isoflavone and alendronate sodium are up to grade;the tablet have moderate rigidity,uniformcolor,homogenous qulity and good break-down character,which all fit to the clinical standard.3.2 Result of pharmacy effacicy3.2.1 Results of biochemical parameters in serumThe Ca in serum decrease and the ALP increase when the ovary were cutted off compared with the sham operation group(P<0.05),which show the rise of bone metabolization,and acceleration of bone transformation.The content for Ca in the mice humerus show decrease when the ovary were cutted off compared with the sham operation group(P＜0.05).and the group A,B,and C show increase in the bone mineral content for Ca compared with the model group(P＜0.05);however,there are statically difference between group B and group A(P＜0.05),group C and group A (P＜0.05);and no statically difference between group B and group C (P＞0.05).When takeing the calcicum cabonate,the ALP show no changing in the group A;however there are significant statical difference for ALP in group B and group C compared with the model group(P＜0.05).3.2.2 The results of bone density for mice femoralThe bone density of model group decrease significantly compared with the sham operation group(P＜0.05);however all the group A,B and C show increase in the bone density compared with the model group significantly(P＜0.05).among the medicine groups,there are statical differences between group B and A,group C and A(P＜0.05).However no statical differences between group B and C(P＞0.05).3.2.3 The microstructure of the bone pathologyThe HE slice show a good structure and unifor thickness of bone trabecular in the sham operation group;however the model group show sparsness of trabecular and decrease in bone cells,the gap between the trabecular are widened clearly;after taking in difference medicine the thickness of trabecular changed in diffferent degrees,the group B and group C show better reslut than group A;but there are no difference between group B and group C.4 Conclusion4.1 The new medicine for treatment of postmenstruation osteoporsis with 4 effective ingrediments are prepared successfully.The content of the calcium carbonate,vitamine D₃,soybean isoflavone and alendronate sodium are up to grade. The tablet have moderate rigidity,uniformcolor,homogenous qulity and good break-down character,which all fit to the clinical standard.4.2 It is hard to get good result for treatment the postmenstrution osteoporosis using the calcuim only.4.3 Using the calcuim combined with the soybean isoflavone could get a good result to treat the postmenstrution osteoporosis just like adding the calcuim into the bone cells.4.4 It may be theorytically ideal to get a compound medicine combined with 4 ingredients together:calcium carbonate,vitamine D₃,soybean isoflavone, alendronate sodium.but our reslut tell that there are no statically difference between the group B(without alendronate sodium) and group C(plus with alendronate sodium),pherhapys there are a unknow ways may affect the absorb rate among the different ingredients.so we should change the technique of medicine production to let the different ingredients of the compound be absorded in different position of the digistive cannal in different times.