| Objective:SA is a major water-soluble components of Salvia miltiorrhiza, with a wide range ofpharmacological effects and clinical applications, especially for the treatment ofcardiovascular diseases. SA has good water solubility, but poor oral absorption andbioavailability. In this paper, SA phospholipid complex was prepared, in order to improvethe oral absorption and bioavailability. Finally, we prepared the SA phospholipid complexdripping pills. It is convenient for patients to take, which laid a foundation for itsindustrialization.Methods and Results:1. Preparation of SA phospholipid complexSA phospholipids complex was prepared by solvent evaporation method. The bindingrate of SA was investigated, single factor test investigation were applied to analyze thetechnological parameters, such as the reaction solvent, the mass ratio of SA and lipid, theconcentration of SA, reaction temperature and time. The optimum process parameters wereas follows: using ethanol as reaction solvent, reagents proportion of SA and phospholipid as1:1, the mass concentration of reaction solution of SA was10mg mL-1, reacting for1h at40℃. In addition, the experiment established the method for the determination of SAphospholipid complex. The results show that, the method is specific, accurately andsensitivity. SA was linear over the concentration range of1~50μg mL-1. The regressionequation as follows: A=18846C-16857, r=0.9997. The content of SA phospholipid complex was34.59±0.46%, which was determined by this method. Finally, NMR and DTA was usedto characterize the phospholipid complex.The results proved complex is not a simplephysical mixture, but the SA and phospholipid binding force through some complexformation.2. Study on the preparation of SA phospholipid complex dripping pillsThe SA phospholipid complex dripping pills were prepared by the melting method.Single factor test investigation were applied to analyze the technological parameters of thesubstrates, the size of dripper aperture, the temperature of the upper condensate, the ratio ofdrugs with substrates and the dropping temperature. The dripper aperture size was2.1/2.5mm(internal/external) and the temperature of the upper condensate was room temperature.The orthogonal test was applied to optimize the parameters with the choice of substrates,the ratio of drugs with substrates and the dropping temperature. Ultimately, the optimumpreparation was as follows: taking PEG6000as the substrate, the ratio of drugs withsubstrates is1:3, the dropping temperature80℃. The content of dripping pills wasdetermined by HPLC. The results of method validation proved that the method is accurateand reliable with good precision and reproducibility.The content of dripping pills wasdetermined as8.11±0.11%. The results of in vitro dissolution experiments show that,compared to SA phospholipid complexe, the dripping pills has been significantly improvedin vitro dissolution of SA.3. SA pill and compound pills pharmacokinetic study in rats after intravenousadministrationHPLC method was established for determination of plasma concentration of SA. Theresults were as follows: SA linear range was0.8~10μg mL-1;the lower limit ofquantification was0.8μg mL-1; the detection limit was0.3μg mL-1; the extractionrecoveries of salvianolic B was greater than85%; the accuracy and precision meet therequirements; the stability of salvianolic B in plasma samples was good. Thepharmacokinetic parameters was determined of SA in rat plasma after oral administration ofSA dripping pills and SA phospholipid complex dripping pills, with dosage (the content ofSA) for500mg Kg-1. The results were as follows: Tmax was33.54min and53.22min, Cmax was2.099μg mL-1and4.248μg mL-1, AUC was7.576μg h mL-1and18.562μg h mL-1. Compared to SA pills, the AUC of SA complex phospholipid dripping pillsincreased2.45times; half-life period was prolonged; the elimination rate constantdecreased. The results illustrated that SA complex phospholipid dripping pills can increasethe bioavailability of SA. |
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