The Structure Optimization Of The Rare Saponin Components Of Anti-lung Cancer Red Ginseng And The Preparation Of Tumor-targeting Binary Mixed Micelles

The incidence and mortality of lung cancer are the highest in China,and are increasing year by year.At present,surgery,chemotherapy and radiotherapy are still the main methods for the treatment of lung cancer.However,the toxic and side effects of anti-tumor drugs used in radiotherapy and chemotherapy are relatively large,which greatly reduces the quality of life of patients.Traditional Chinese medicine has higher safety and low toxicity,so it has been widely used in recent years for the treatment or adjuvant treatment of tumor diseases.However,traditional Chinese medicine still has the problems of complex components and rich activities,so it is difficult to accurately interpret the active ingredients and efficacy.These defects make it difficult to carry out effective quality control and limit the development of traditional Chinese medicine as raw material.In order to solve this problem,it is necessary to clarify the material basis of Chinese medicine.After many years of research on the material basis of traditional Chinese medicine,our group put forward the theory of?composition structure?of the material base of traditional Chinese medicine:traditional Chinese medicine as an orderly whole,there exists a certain dose-to-ratio relationship between components and components within each component.In this particular dose-to-ratio relationship,the best pharmacodynamics of traditional Chinese medicine can be brought into play.Therefore,we refer to this ratio as the structure of components,which can explain the material basis of traditional Chinese medicine.Ginseng is a kind of traditional Chinese medicine which contains ginsenosides,polysaccharides,peptides and fatty acids.The research shows that ginsenosides and polysaccharides play a major role in ginseng.Since 1968,advanced researchers in various countries have begun to study the antitumor effects of ginsenosides.Clinically,monomeric preparations of ginsenosides have been used as tumor angiogenesis factor inhibitors for the adjuvant treatment of tumors.However,the study of ginsenoside on tumor was limited to the study of single component or crude extract,which could not fundamentally explain the pharmacological basis of ginsenoside against tumor,and the biopharmaceutical properties of each component were not clear.To a large extent,the development of its preparation is limited.Based on the theory of component structure,we studied the material basis of ginsenosides and optimize the composition of the components by in vitro and in vivo anti-tumor efficacy experiments.We designed new formulations of ginsenosides by new nanotechnology to increase the solubility of components and the targeting effect of lung cancer.The main contents of the study are as follows:1.Structural optimization and superiority evaluation of Rare Hongshen Saponin Components directed by anti-tumor activity.The components of ginsenosides Rh₁,Rb₁,Rg₁,Rd,CK,Rh₂,and Rg₃,which are representative components of anti-tumor efficacy of ginsenosides,were optimized for composition.According to the contribution of different components to the overall anti-tumor effect,it was determined that ginsenoside CK,ginsenoside Rg₃ and ginsenoside Rh₂ were the representative components of ginsenoside to exert its antitumor effect,namely,Rare Hongshen Saponin Components?RHSCs?.The anti-tumor efficacy of RHSCs on A549 cells was evaluated as an index.The ratio design was combined with a non-linear surface mathematical model to optimize the structure of RHSCs,and the optimal components of Rare Rengshen Saponin Components were obtained.The optimum proportion of the representative components is ginsenoside CK:ginsenoside Rg₃:ginsenoside Rh₂=4.1:2.6:3.3.And the in vitro and in vivo anti-tumor experiments were used to verify efficacy.The results showed that the antitumor effect of the optimized RHSCs was superior to that of a single component,and RHSCs could inhibit the migration of tumor cells and promote cell apoptosis.2.Evaluation of physical and chemical properties of RHSCs and preparation of mixed micellesIn this part,the physical and chemical properties of the RHSCs are characterized,and the equilibrium solubility and apparent oil-water partition coefficient of the RHSCs are measured.The similarity of the components in the RHSCs is detected by using the angle cosine function.Euclidean distance was used to measure the dispersion of each component,and the mass weight coefficient was introduced to characterize the solubility and oil-water partition coefficient of the RHSCs.The RHSCs mixed micelles?RHSCs-M?were prepared by thin-film dispersion method.Solutol^?HS15 and TPGS were used to prepare mixed micelles.Solutol^?HS15 has good biocompatibility and solubilization.TPGS can reverse P-pg and reverse multidrug resistance.It has been approved by the FDA as a safe injection excipient.The particle size,potential and morphology of the RHSCs-M were characterized by particle size analyzer and transmission electron microscope.The prepared mixed micelles can greatly increase the solubility of the RHSCs,the solubility of which is increased by more than 500times,the micelle size is uniform,and it is spherical or spherical.The average particle size is47.32 nm,the entrapment efficiency is 96.02±0.85%,and the drug loading is 6.69±0.07%.3.Tumor targeting of RHSCs-M and evaluation of anti-tumor effect in vitro and in vivo.Another factor restricting the effect of antitumor drugs is the poor targeting of tumor.In this part,the uptake of mixed micelles by tumor cells was simulated by means of in vitro cell uptake experiments with fluorescent dyes instead of drugs.The in vivo tumor targeting of mixed micelles was detected by in vivo imaging.The results showed that the mixed micelles carrying fluorescent dyes reached the tumor site at 4 h.After 24 hours,the tumor site still has fluorescent expression,indicating that mixed micelles can effectively increase the targeting of RHSCs to lung cancer.In vitro and in vivo cell experiments were used to verify the enhanced effects of the RHSCs-M on the RHSCs.After the preparation of RHSCs-M,in vitro and in vivo,the inhibition of cell proliferation was enhanced,and the RHSCs-M had no inhibitory effect on the immune system and have high safety..