Bioavailability of magnolol

In view of the problems such as poor water solubility and low oral bioavailability of magnolol, a systematic study was carried out on the magnolol phospholipid complex prepared by solvent method, with a view to increasing its oral absorption and improving bioavailability. The main research content is as follows. (1) The evaluation criteria for the preparation conditions of the precipitous magnolol phospholipid complex were established, that is, the compound rate of the magnolol and phospholipids, and the effect of the preparation process conditions such as the type of reaction solvent, the input ratio of phospholipid and the original drug, the reaction concentration, reaction time and reaction temperature were established, and the preparation process conditions were verified. The results show ratio of reaction solvents as the key process conditions for preparation, and the verified preparation process conditions are: the reaction solvent is tetrahydrofuran, and the ratio of phospholipids to magnolol feed is 3:1,40 degrees C. (2) The content of the magnolol phospholipid complex was determined by high-efficiency liquid chromatography, and the measurement method was systematically and comprehensively verified according to the test ingress with the guiding principles of drug quality standards. The verification results show that the method has high sensitivity and accuracy, good repeatability and durability, and can be used as a method for measuring the content of the phospholipid complex. (3) The physical and chemical properties of the magnolol phospholipid complex were studied by means of ultraviolet spectroscopy, scanning heat, X-ray powder diffraction, infrared absorption and nuclear magnetic resonance, and the formation mechanism was discussed. The results show edify the crystal characteristics of the phenol after forming a compound with phospholipids, showing amorphous characteristics, and being highly dispersed among phospholipid molecules. The corresponding infrared signal of the pre-phenolic benzene ring skeleton or its phenolic hydroxyl and phospholipid polar end changes, but the non-polar end of phospholipid still retains the original infrared characteristics, it is assumed that the combination of the two should occur in the benzene ring skeleton of the magnolol or its phenolic hydroxyl and phospholipid polar base site. The proton signal of the magnolol in the nuclear magnetic resonance hydrogen spectrum of the magnolol phospholipid complex is significantly weakened, presumably due to the binding of the polar ends of the magnolol and phospholipids, which are caused by the cladding of its free-rotating fatty acid chain, and by the absence of a new proton signal, further indicating that the two are composites formed by the binding of the forces between the molecules. instead of generating new compounds. The influence factors and accelerated test results show that compared with the original drug and its physical mixture, the phenolic hydroxyl in the compound is combined with the extreme end of phospholipid, the fatty acid chain reduces the influence of oxygen, photoenergy and so on the easily oxidized part of the magnolol and the thermal stability is significantly improved. (4) The apparent solubility of the magnolol phospholipid compound and the magnolol phospholipid complex in water improved to varying degrees, but the apparent solubility of the precision phospholipid physical mixture in water was greater, and the difference showed that the formation of the molecular inter-molecular force in the magnolol phospholipid complex changed the dissolving characteristics of the two. There was no significant difference in the solubility of the magnolol phospholipid compounds in the pH1.2 to 8.0 range, indicating that the solubility of magnolol was non-pH-dependent in the physiological acidity range. The results of in vitro solubility experiments show that the dissolved velocity of different pH-soluble media without surfactants has no significant effect on the solution rate of magnolol, magnolol phospholipid compound and magnolol phospholipid complex, but as an external mechanical force, different solubility transfers can affect the diffusion of the drug in the dissolved medium in the compound. (5) The pharmacokinetic study of pharmacokinetics in rats was carried out to compare three sets of pharmacokinetic characteristics and oral relative bioavailability, respectively, by giving the same dose of magnolol, magnolol phospholipid physical mixture, and magnolol phospholipid complex, respectively, to compare the three sets of pharmacokinetic characteristics and oral relative bioavailability. The results showed that compared with the original drug, the main pharmacodynamic parameters of C max, T max, AUC and MRT were significantly different, and oral bioavailability was improved by 97% in the experimental measurement time range, and a certain amount of slow release characteristics were shown. The analysis of the results of the in vivo study showed that the presence of molecular inter-molecular forces after the formation of a compound by magnolol and phospholipids and the protokinity of the magnolol caused the prosusal effect of the phospholipid to spread from phospholipids into the body fluid or cell membrane bilipid layer was delayed, and its invival pharmacodynamic characteristics were distinguished from the physical mixture that increased the water solubility of the preluscent simply by increasing the solubility. It is shown that phospholipid complexes can improve their oral bioavailability by increasing their solubility in the solution and prolonging the duration of drug action. (6) On the basis of the data on the external release degree and the concentration of blood medicine in the body obtained by the magnolol phospholipid composite object, the correlation between the body and the inside and outside was established and analyzed by the convolution method and the anti-convolution method respectively, and the difference between the two methods was compared, especially for the fluctuation of experimental data. The paper integration method can be better fitted than the anti-volume integration method, and the in vitro release determination conditions for screening out are: oars, 100 revolutions, dissolved media for 1% SDS 1000mL aqueous water solution, laying the foundation for the future establishment of quality control indicators of the preparation of the magnolol phospholipid compound. In summary, innovative research and exploration has been carried out in the following five areas: (1) the production of magnolol into phospholipid complexes, which have not yet been reported at home and abroad; Through the study of pharmacokinetics in rats, it was found that after making phospholipid complexes, the properties of the phospholipid compound showed certain slow release characteristics in the body, and no relevant research reports were reported at home and abroad; (4) the internal and external correlation of the magnolol phospholipid complex was compared by the method of volume/anti-volume integral, and the importance of the selection of the parameters was proved by comparison. It is proposed to correct the calculation process with the AUC ratio of the reprieve and the reference formulation as a corrective factor, and (5) to screen and determine the determination conditions of the out-of-scope degree of the magnolol phospholipid compound object based on the study of internal and external correlation, and no relevant research reports have been reported.


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