| Chinese medicine active ingredients is mainly obtained by separation and extraction method, however, many active ingredients such as paclitaxel, epimedium and ginkgo lactone, etc, which is difficult to prepare a lot, and the oral bioavailability of Chinese medicine active ingredients is low, limiting its clinical efficacy.Ginseng rare ginsenoside Compound K (CK) is one of the five plus families,and is a kind of pa-nax ginseng glycol type rare ginsenoside.which are widely used in disease prevention and treatment v-arious countries. In recent years, the study found that ginseng saponin CK is the strongest one of t-he rare ginsenoside which has obvious effec in antitumor, anti-diabetes, nerve protection, anti-aging, a-ntiinflammatory, antitumor activity in ginseng saponin, has a strong development potential.Studies hav-e shown that CK content is low in plants, simple separation which is difficult to meet the applicatio n requirements, and it difficult to soluble in water, oral dissolution rate is slow, there are serious P-gp efflux, leading to its low oral bioavailability, and limits the curative effect.To solve these problem-s, the author adopts the method of biological enzymolysis to solve preparation of rare ginsenoside CK, and mixed micelle preparation technique to improve the bioavailability.The snail enzyme is proposed for the first time to prepare CK, the writer studies the snail enzy-me hydrolyze Rb1 to prepare CK,and further studied the various factors which influence the ginseng rare ginsenoside Compound K conversion, and response surface method design is used to optimize t-he preparation conditions.On the basis of which the author research the basic biological transformation method to do the further, proposed the ultrasound Assisted the Enzymolysis of Ginsenosides and snai-Iase immobilization onto microspheres to prepare of CK that two kinds of research to have carried o-ut in-depth research work. Snailase is used for the enzymolysis between the ginsenosides and the rar e ginseng saponin Compound K. In total ginseng saponin preparation CK ultrasound-assisted enzymati-c studies,Furthermore, Considering the bioconversion rate as the target, the effectiveness of ultrasonic pretreatment factors, such as ultrasonic power and ultrasonic time, and enzymatic hydrolysis factors, s uch as pH value, temperature, concentration of substrate, dosage of enzyme and reaction time, on the bioconversion rate is studied under single factor. Besides, response surface method design is used to optimize the preparation conditions. As to select the best preparation technology.Considering the enz-yme activity recovery rate as the target, crosslink-embedding method is used for preparing the snailas e immobilization onto microspheres and preferring the best preparation by orthogonal test. Furthermore, enzyme characterization of the optimum temperature, optimum enzymatic properties of pH value, ther mal stability, pH stability and storage stability was studied, and the effectiveness of temperature, conc entration reaction time, and transformational times on the bioconversion rate was studied to optimize t he preparation conditions. Preparation of CK is used to the study behind, according to its biopharmac eutical properties to design dosage form.With vitamin E polyethylene glycol 1000 succinate and soybe -an lecithin as the carrier, Bying solvent evaporation method to prepare mixed micelles, the orthogona-1 design is used to screen the best preparation technology;Investigating morphology, particle size, coat ing rate, drug-polymer interactions, in vitro release degree;And through the Caco-2 cell model to eval uate its transport absorption characteristics and in vivo bioavailability evaluation in rats.Snail enzyme convert Rb1 to prepare CK which research results show that the enzyme hydrolysis method as a kind of green, safe method, and is able to keep the product structure, more suitable for industrial production. The optimum enzymolysis with snailase was achieved at 50 "C, pH 5.5 of the acetic acid-sodium acetate (1:1) buffer solution for 36h. The substrate concentration is 1.0 mg-mL-1. With the above conditions, the bioconversion rate is 86.91%, and it’s structure was elucidated on t he basis of its spectral evidences. Experiencing, optimize the predicted results are in good agreement with the experimental results. In addition, the research group is also studying the rare ginseng saponi n other monomers, in order to provide the material basis for the study of rare ginseng saponin comp onents, so as to medicine rare active ingredients in new product development provides an effective m-eans.The results of ultrasound assisted enzymatic preparation of ginsenosides rare ginseng saponin Co-mpound K shows that the use of ultrasound-assisted enzymatic method, rare ginseng saponin CK conv-ersion rate increased from 3.27% to 6.91%. The main reason is the use of ultrasonic cavitation, vibr-ation, thermal and mechanical action, prompting the substrate with the enzyme into tiny particles, the contact area increases, more fully combination further facilitates play Snailase enzymatic hydrolysis.Microspheres immobilized enzyme preparation findings snail rare ginseng saponin CK show that t-he thermal stability of the immobilized enzyme snail, pH, stability and enzyme immobilization snail-shelf life have been effectively improved; at the same time, snail enzyme immobilization structure ma-y protect the enzyme and enzymatic changes in the environment without change; and the immobilize d enzyme may be separated by a simple method such as filtration or centrifugation, and then recyclin g-g. Therefore, the present study is to improve the immobilized enzyme snail conversion efficiency, e-xpand the scope of application to provide practical experience and theoretical basis.This study with vitamin E polyethylene glycol 1000 succinate and soybean lecithin as the carrier, rare ginseng saponins prepared by solvent evaporation method Compound K mixed micelles, the orth ogonal design to screen the best preparation technology;Investigate morphology, particle size, coating r ate, drug-polymer interactions, in vitro release degree;And optimization through Caco-2 cell model to evaluate the transshipment absorption characteristics.The results showed that the best preparation techn-ology for mixed micelle ginseng saponin rare CK inventory 1.0 mg, vitamin E, polyethylene glycol 1 000 succinate and soybean phospholipid proportion of 1:1, hydration volume 10 ml;Preparation of mix ed micelle spherical or spherical, the average particle size was 110±2.69nm, average coating rate w-as (92.23±2.76)%, the average drug loadings was (4.32±0.19)%.In vitro release of the experimen-t al results show that the mixed micelle has certain slow-release ability.Caco-2 cells model shows that mixed micelle promote the absorption of the CK, and outside have certain weakened.Bioavailability of the research results show that after preparation of CK mixed micelle, due to i-mproved the dissolution of active pharmaceutical ingredients, so as to promote the absorption, improv-e the bioavailability.For TPGS and soybean phospholipid as carrier of ginseng saponin CK rare mixed micelle, on the one hand, due to the carrier TPGS effectively restrain the P-gP outside and soybean phospholipid biocompatibility;On the other hand, after mixed micelle formation, drugs to core exists in hydrophilic shell, effectively improve the dissolution of the drugs, the role of the two aspects joint ly promote the drug absorption and improve the bioavailability.Comprehensive experiment indicated above, the author successfully optimized the optimum digesti-on conditions of CK, and to improve the CK conversion from two different angles, and then combin ed with biopharmaceutical characteristics of active pharmaceutical ingredients, with TPGS and soybean phospholipid as joint carrier preparation of ginseng saponin CK rare mixed micelle, significantly enh ances the dissolution of active pharmaceutical ingredients, rare for ginseng saponin CK high oral bioa vailability of the reference for the research and development. |
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