Synthesis Of Alendronate Coupled Lipid Molec?les And Preparation Of Liposomes

The incidence of multiple myeloma in the middle-aged and elderly population is increasing.Due to its inherent or acquired resistance,multiple myeloma is still an incurable disease.In this paper,bortezomib is used as a model drug to prepare its liposome preparation,and its preparation process and formulation are optimized.Further,bone targeting molecules with bisphosphate as the target group are synthesized.The basic characteristics of bortezomib bone targeting liposome are explored,and the relationship between the structure of bone targeting molecules and the properties of liposome is discussed,providing theoretical guidance for the study of bone targeting preparations.According to the physical and chemical properties of bortezomib,two analytical methods,ultraviolet spectrophotometry and high performance liquid chromatography,are established.UV spectrophotometry selected 270 nm as the detection wavelength,established a good linear relationship between 0-30 ?g/mL of bortezomib,and investigated the precision,daytime tightness,recovery and stability of bortezomib.RSD is less than 2%,which is reasonable and effective.HPLC established 0-50 of bortezomib The results show that the RSD is less than 2%,which is reasonable and effective.The preparation method of liposome is selected,and ethanol injection method is determined to be the better preparation method in this experiment,and the preparation process is optimized.The average entrapment rate of BTZ lips is 30.75%,the average permeability is 2.44% and the average particle size is 67.57 ± 2.43 nm(n = 3)in 20 days after storage at 4?.With lauric acid as the starting material,HOSU activates the carboxyl group in lauric acid structure to form the intermediate structure lauric acid active ester,which reacts with alendronate to form alendronate sodium coupling lauric acid.The molar mass ratio of lauric acid to HOSU is 1:1.2,the amount of coupling agent Hatu is 1.5 times the molar mass of lauric acid,the reaction temperature is 0?,the reaction time is about 24 hours,and the organic base diea 5 times of the molar mass of lauric acid,eluting with ethyl acetate,the yield reached 63.2%;the lauric acid is coupled with alendronate by the reaction of lauric acid active ester and alendronate sodium,the molar mass ratio of lauric acid to alendronate sodium is 1:2.5,the volume ratio of water phase to organic phase is 5:2,the post-treatment solvent is dichloromethane,the yield is 29.37%.The products are identified by NMR.The results showed that the average entrapment efficiency of ALE-BTZ-LCL is 24.23%,the average entrapment efficiency of ALE-BTZ-LCL is 42.85%,the average permeability within 20 days is 2.34%,and the average particle size is 110.5±3.6 nm(n=3);the release of ALE-BTZ-LCL,free BTZ,BTZ-Lips,BTZ-LCL is investigated in vitro,and the release of ALE-BTZ-LCL is recorded In the process and cumulative release rate,liposome have a sustained release effect compared with free drugs,and ALE-COOH does not affect the release efficiency of BTZ.