Soy Isoflavones Solid Dispersion Of Fragments, Preparation And Preliminary Study Of The Pharmacokinetics

Soy-isoflavone mainly reside in fabaceous pod, has a high contents in soy bean, distributed in seed leaf and hypocotyls of soybean seed, has a less contents in testa. Now, 12 kinds of Soy-isoflavone has been found, included 9 kinds of soy-isoflavone glycoside and 3 kinds of corresponded aglycone.Soy-isoflavone is the active component of the most medical treatment value in the soybean biological actives, which has estrogen function, including anti-tumor, antioxygen, heart-blood vessel protection, improving bone rarefaction and relieve the indisposition symptom of female climacteric state. so, it has the high value of studying and developing. But, as soy-isoflavone is indissolvable in water, has very low bioavailability, which bring some difficults for its clinical application. Howerer, solid dispersion is one of the technologies of increasing the bioavailability of indissolvable drug, which force drug being at high disperdion state, Generally, drug particle diameter in solid dispersions was 0.001～0.1um, mainly dispersed condition was molecularity, metastable amorphism and colloidal state. Carries' wettability, restrain crystallinity to drug assured drug's quickly dissolution, the bioavailability of drug has corresponding increase, usually, the preparative method of solid dispersion was solvent co-evaporation, fusion method, and solvent-fusion method. The common water solubility carries was peg, pvp, poloxamer, organic acid, and saccharide.The purpose of this study is designing an effective oral administration preparation by using solid dispersion technology to increase the bioavailability of soy-isoflavone.Soy-isoflavone solid dispersion was prepared in the study, the influence of different carriers (peg4000,peg6000,poloxamer188,pvpk30) and preparative method(solvent co-evaporation, fusion method) to the dissolution rate of soy-isoflavone was considered, moreover, the dissolution data was been taken curve fitting by weibull equations, and comparing their dissolution parameters, and concluded that the dissolution rate of soy-isoflavone was highest when using pvpk30 as carriers and applying dissolvent co-evaporation method. The influence of different amount of carriers to the dissolution rate of soy-isofiavone was further considered, as a result, the dissolution rate of soy-isoflavone was highest when pvpk30: drug=9:1. The diferential thermal analysis (DTA) test show that soy-isoflavone is dispered in pvpk30 in amorphism. Comparing solid dispersion with physical mixture and pure soy-isoflavone was showed that the dissolution rate of soy-isoflavone solid dispersion was highest.In the influencing factor experiments of soy-isoflavone and its solid dispersion, at the condition of high temperature, high moist and highlight, the appearance, content and dissolution of soy-isoflavone has no marked change, at the condition of high temperature and highlight, the appearance, content and dissolution of soy-isoflavone solid dispersion has no marked change, at the condition of high moist, the appearance of soy-isoflavone solid dispersion has marked change, showing severe hydroscopicity, contents and dissolution has no marked change.During the study of preparing soy-isoflavone solid dispersion tablet, disintegration time and dissolution rate of soy-isoflavone solid dispersion tablet was considered as inspection items, tempering uniformity design method was applied to optimize preparation prescription, partial least square method regression analysis was used to modeling for the data of uniformity design, the calculate results was consistent with the experiment validation results, and concluded that the optimizing prescription of soy-isoflavone solid dispersion tablet was Soy-isoflavone solid dispersion 0.18g, Amylum Pregelatinisatum 0.26g, CMSNa 0.03g, Gum Acacia 0.03g. The tablets of soy-isoflavone solid dispersion has good appearance, the contents of total isoflavone in tablet was detected by UV, and the contents of genistin was detected by HPLC. The comparation of dissolution rate between the soy-isoflavone solid dispersion tablet and its normal tablet was showed that the dissolution rate of soy-isoflavone solid dispersion tablet was higher than its normal tablet. six months' accelerated test show that the dissolution of soy-isoflavone solid dispersion tablet has some extent decline, but the final dissolution was still kept above 80%.During the study of pharmacokinetics of soy-isoflavone solid dispersion tablet and its normal tablet in rats, the time-variation curve of the concentration of Genistein which was the metabolic product of soy-isoflavone in blood was described, the fitting parameter of the pharmacokinetics software(DAS) show that the rats administered soy-isoflavone solid dispersion tablet was found in their blood the Genistein's Tmax was faster, Cmax was higher, and bioavailability was higher.As a result, soy-isoflavone solid dispersion tablet in the study reach its purpose of increasing bioavailability.