Studies On Jinlingzi Decocting Technical Standardization And Solid Dispersion

Jinglingzi pulvis,as the representative of analgesic drugs,is often administrated in the form of decoction.However,due to the lack of a corresponding complete specification in decocting process,and different decocting methods can affect the content of active ingredient decoction,thereby affecting the efficiency of the treatment.So that the stability and efficiency of the decoction can not be guaranteed.The main active ingredients of Jinglingzi decoction are alkaloids,because of its high liposolubility,poor water soluble,low bioavailability,worse oral absorption and slow onset,the efficacy is difficult to play.Solid dispersion,as a novel drug delivery system,can improve the dissolution rate,solubility and bioavailability of insoluble ingredients in traditional Chinese medicine,and inhence the efficiency of treatment.Thereby,it provide a new impetus for improving the competitiveness of Chinese medicine and making it to go abroad.In this study,we have chosen Jinlingzi pulvis as a representative of decoction,then chosen five active ingredients and extract rates as the index,at last,we have developed the best decocting technology to guarantee the efficacy.At the same time,we chosen PEG 6000 and F-127 as accessories,and selected tetrahydropalmatine as the representative of the active compounts in Jinlingzi pulvis,Jinlingzi solid dispersions were prepared,the bioavailability of tetrahydropalmatine,tetrahydropalmatine solid dispersions,Jinlingzi decoction,Jinlingzi solid dispersions were compared.We have also elaborated the rationality of compatibility,and confirmed that solid dispersion can promote the absoption of medicine.Our subject includes the following sections:1.We have chosen five active ingredients and extract rates as the index,established the best decocting technology.(1)An accurate and efficient determination method of five active ingredient content have constructed.(2)We have chosen five active ingredients and extract rates as the index,established the best decocting process by single factor and orthogonal experiments.The best decocting process is adding 10 times water of drugs,soaking for 45min,decocting 2 times for each 30min.Futhermore,soaking time had greatest influence.It was recommend that we should increase the soaking time when decocting the hard texture medicine such as roots.2.The preparation and characterization of tetrahydropalmatine solid dispersions(1)The study of physical and chemical properties of tetrahydropalmatine:The solubility in water was 24.96 ?g·mL-1,which indicated that tetrahydropalmatine had very slightly soluble.The Oil/Water apparent partition ranged from 0.23 to 394.53 in different pH aqueous solution,the range of log Ko/w was from-0.65 to 2.59,which indicated that it had high liposolubility,and was not in favor of absolution.Stability studies had found that when the temperature was higher than 60 ?,the degradation speed would be significantly fast.(2)Prescription of solid dispersion and optimization of preparation:In the study of optimization of solid dispersion preparation system,dissolution and solubility of tetrahydropalmatine indicators were used to screen the polymer materials,PEG 6000 and F-127 were most satisfactory.So we chosed them as the polymer of solid dispersion.The ratio of F-127 and PEG 6000,mixed carrier and drug ratio,solvents,rotary evaporation temperature were investigated by single factor investigation.Larger impact factors by orthogonal experiments were selected to determine the best preparation technology,and its dissolution curve was fitted,its dissolution way was also revealed.(3)Characterization and investigation of the physical and chemical properties:Solid dispersions,tetrahydropalmatine and physical mixtures were characterized by X-ray diffraction analysis(XRD)and differential scanning of calorimetry(DSC)to reveal the the existened forms of tetrahydropalmatine in vector.It was found that the solubility of the drug in different pH solutions have increased,and the oil-water partition Ko/w value was decreased when in solid dispersions,indicating that the technology had increased the drug's water-soluble.3.The pharmacokinetic studies of tetrahydropalmatine in rats(1)An accurate and efficient determination method of tetrahydropalmatine in rats had constructed.(2)The absolute bioavailability of tetrahydropalmatine in rats:The pharmacokinetic parameters of tetrahydropalmatine showed that the absolute bioavailability was only 6.59%after intragastric administration and intravenous injectionand in rats,which indecated that absolute bioavailability of tetrahydropalmatine was very low in rats.We had compared the pharmacokinetic parameters of tetrahydropalmatine,Jinlingzi decoction,tetrahydropalmatine solid dispersions,Jinlingzi solid dispersions,determined the plasma concentration at different time points byHPLC,and found that the bioavailability of Jinlingzi decoction was 1.6 times higher than the monomer compound.When prepared in solid dispersions,the bioavailability of the drug werel.6 times and 4 times of anterior,which reflected the rationality of Chinese medicine compatibility,and the superiority of solid dispersion.