| Objective: Bile salt/phosphatidylcholine mixed micelles system (BS/PC-MMS) is a biocompatibility supporter,which can improve the solubility of poorly soluble drugs, and it is possibly can enhance the therapeutic effect . This system is generally used for solubilization of indissolvable drugs ,and research less at home. Puerarin is widely attentioned for its abundant source and good therapeutic effect. Because of it poor absorption, its chief administration is puerarin injection.It is mainly used clinically for treatment of cardiovascular system diseases. With the increasing of reporters to the adverse drug reactions (ADRs), perhaps it will be an effective method to lower or avoid its ADRs that exploring the oral medication with hight bioavailability of puerarin or finding hypotoxic injectable accessories. Because of the poor water-solubility of injection and poor bioavailability of oral administration, the difficulty to explor or improve the puerarin preparation is to raise its water-solubility then the bioavailability. So the BS/PC-MMS is used to improve the solubility and bioavailability of Puerarin in this reseach.And provid experience for the apply of Bile salt/phosphatidylcholine mixed micelles system at home.Method:(1)Study on the preparation conditions of the BS/PC-MMS of puerarin(PMMS): To obtain the best preparation conditions ,solution percentage appearance morphosis and particle diameter is used to evaluate the influence to the preparation,from which we can obtain the ratio of the drug and accessory the ratio of accessories and the temperature.And we also had measured its solubility(.2)Study on the absorption in rat small intestine: The experiments of the absorption of puerarin and the PMMS were carried on in small intestine of rat respectively, and compared the absorption rate of puerarin at 3 hour. Furthermore, compare the volumetric remedy method and metered volume remedy method of the rat small intestine experiment。(3)Study on the absorption in Beagle dogs: The experiments of the puerarin injection the absorption of puerarin and PMMS, were carried on Beagle dogs, to abtain the absolute bioavailability and the relative bioavailability of PMMS.(4)Distribution of PPMS in heart, liver, spleen, lung, kidney of rats was primarily carried out.Result: (1) The best preparation conditions for the PMMS is: The Puerarin : Soya phosphatidylcholine:Sodium deoxycholate is 3:2:4 (mole ratio), and the temperature 30℃. The particle diameter is 64.8±13nm(volume-weighted particle size distribution). Its solubility is 56.4﹥mg/100ml in water in the room temperature which is 122 times compared with literature. It shows that BS/PC-MMS can imprve the solubleness of Puerarin well。(2)The absorption rate of PMMS at 3 hour show that the BS/PC-MMS can't improve the absorption of Purarin obviously.And the results of the volumetric method and metered volume method of the rat small intestine experiment is alike。Maybe Puerarin can be absorbed at other places.(3)The absolute bioavailability of puerarin is 6.4%, the absolute bioavailability of PMMS is 32.1%, while the relative bioavailability of PMMS is 501.1%。The results of statistical moment is the absolute bioavailability of puerarin is 5.7%,the absolute bioavailability of PMMS is 29.9%;while the relative bioavailability of PMMS 708.5%.It shows that BS/PC-MMS can imprve the absorption and bioavailability of Puerarin well.(4) Distributions in main organs (liver, heart, spleen, lung, kidney, brain) were observed after oral administration of Puerarin crude drug and PPMS. And it increase the distribution obviously in every main tissue after ig PPMS ,comparing with ig crude drug.Conclusion: By the ways of preparing the PMMS, the solubility of puerarin in water can be increased significantly. |
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