| Diabetes is a problem that plagues the medical community.It is the goal of pharmacy workers to develop effective natural non-toxic side effects.1-deoxynojirimycin(1-DNJ)is present in Folium Mori and has a blood sugar lowering effect.The content of this study was to extract 1-DNJ extract from Folium Mori and further purify to obtain high purity 1-DNJ.Animal pharmacodynamic experiments were performed with high-purity 1-DNJ to verify that high-purity 1-DNJ has a hypoglycemic effect.1-DNJ controlled-release pellets were prepared by high-purity 1-DNJ as raw materials,adding suitable excipients,preparing pellets by extrusion spheronization method and fluidized bed coating method.Explore the preparation process of controlled release pellets and examine the main process parameters.Quality control of controlled release pellets.The methodological study and verification of optimized quality control of controlled release pellets.The dissolution curve of 1-DNJ controlled release pellets in the dissolution medium of different pH dissolution media in vitro was predicted to be in the pH of 1.2 in human stomach and gradually changed to pH 6.8 in the intestinal tract after oral controlled release pellets.Dissolution behavior.In the pharmacokinetic study of animals,a comparative study on the pharmacokinetics of 1-DNJ purified and 1-DNJ controlled-release pellets was performed to investigate the effect of 1-DNJ in vivo.Enzymatic hydrolysis of plant cell walls by cellulase method is beneficial to the dissolution and dissolution of active ingredients.In this study,1-DNJ was extracted by single factor,and the optimal extraction range of each extraction factor was finally determined.The optimum extraction conditions for cellulase extraction were optimized by Box-Behnken design center combination method.The 1-DNJ extraction yield was used as the response surface to analyze the interaction between various factors,and the optimal extraction process and conditions were determined by the response surface methodology after the experiment.Since 1-DNJ is a sugar analog,the structure is simple and special,and other chemically similar components coexist.Therefore,there are few methods suitable for separation and purification.At present,the more efficient purification method adopts ion exchange method,because the chemical molecular structure of 1-deoxynojirimycin contains-NH,and the state exists in the acidic and neutral environment of plants.In the positive ion form,this study used the cation exchange resin method to adsorb 1-DNJ from the crude extract,and then selected the appropriate elution solvent for elution to study the adsorption characteristics of 1-DNJ in the cation exchange resin.The 1-DNJ separated from the 1-DNJ in the cation exchange resin is used to remove the other inactive components and other ineffective impurities,and finally the ultrafiltration membrane is used to remove other macromolecules,such as some macromolecules.Sugars and macromolecular proteins,etc.,to achieve separation and purification purposes,and finally get a high concentration of 1-DNJ.The pharmacodynamics experiment of 1-DNJ was carried out using rabbits as experimental animals.In this experiment,maltose and sucrose were used as substrates to study the inhibitory effect of 1-DNJ on ?-glucosidase.In this study,the 1-DNJ controlled release pellets loaded pellet core was prepared by extrusion spheronization method.The controlled release film coating were coated by fluidized bed.The controlled release coating of the pellets enables the s ow release of 1-DNJ at a constant rate,and can regulate the release rate of 1-DNJ controlled release pellets in the stomach and small intestine,so that 1-DNJ can continue to play slowly and stably.Reduce the efficacy of blood sugar.In addition,the 1-DNJ dissolution behavior curve experiment was also carried out in vitro.The rate of 1-DNJ release of 1-DNJ in pH 1.2,pH4.5 and pH6.8 was in accordance with the design requirements.Since there is no chromophoric group in the chemical molecule of 1-deoxynojirimycin,high-performance liquid-liquid ultraviolet detection cannot be directly used.Qualitative and quantitative methods for the extraction and purification of 1-deoxynojirimycin from mulberry leaves were studied.A high performance liquid chromatography(Fluorescence)method was developed using a ruthenium methoxychloride precolumn derivatization method.Quality stability of 1-DNJ controlled release pellets.Accelerated experiment:The condition was relative humidity of 75±10%and temperature of 40 ± 3? for 6 months.Samples were taken at 0.1,2,3,and 6 months to examine the properties,content,and dissolution profile of the pellets.Long-term experiment:The condition is 60±10%relative humidity,temperature 25±3?,and placed for 24 months.Samples were taken at the end of 0,3,6,9,12,18,and 24 months to investigate the properties of the pellets content and dissolution curve.In vivo pharmacokinetic experiments were carried out,and Beagle dogs were selected as pharmacokinetic test animals,and the blood concentration of the dog was compared and processed.The 1-DNJ peak concentration Cmax(?g/L)and the peak time tmax(h)were measured using actual values.The maximum blood concentration Cmax after oral administration and the maximum Tmax value of blood concentration were compared,and the controlled release effect of 1-DNJ controlled release pellets in vivo was compared.The bioavailability was calculated and the relative bioavailability of 1-DNJ controlled release pellets was investigated.The optimum conditions for 1-DNJ were as follows:extract temperature was 56?;material liquid concentration was 0.76 kg/L;extraction pH was 4.2 and cellulase concentration was 3.3 mg/mL.The optimal cation exchange resin was finally optimized to purify the I-DNJ process;the ammonia concentration was 0.5 mol/L,the elution rate was 1 mL/min,and the upper column concentration was 1.5 mg/mL.After purification,the percentage of 1-DNJ was 5.48%.After purification by 816 chlorine-type anion exchange resin,the purity of 1-DNJ reached 1 0.24%.Finally,the ultra-filtration treatment of 1-DNJ reached 19.83%.It is indicated that after a series of purifications of 1-deoxynojirimycin,the purity of 1-DNJ is significantly improved.Pharmacodynamic experiments showed that 1-DNJ inhibited the maltase and sucrase on the intestinal mucosa of rabbits to a certain extent.The higher the purity of 1-DNJ,the stronger the inhibition effect.Extrusion-spheronization method was used for extrusion speed of 300 r/min,spheronization speed of 900 r/min,and spheronization time of 10 min.Fluidized bed coating process adhesive povidone K 30 dosage 6%,porogen polyethylene glycol 6000 dosage 25%,controlled release coating material Hydroxypropyl methyl nanocellulose phthalate weight gain is 12%.The preparation of the pellets is high in efficiency,the particle size distribution of the pellets is uniform,the surface is smooth,the roundness is good,the amount of the auxiliary materials is small,and the drug loading is high,which is a relatively advanced method for preparing the pellets.High-performance liquid phase detection of 1-DNJ content was verified by linearity,limit of quantitation,precision,accuracy and durability.The method has high detection accuracy.The 1-DNJ controlled release pellets were tested for acceleration and long-term stability,and the appearance of the pellets was unchanged,which was white pellets.The 1-DNJ content and dissolution profile of the pellets did not change after 6 months of acceleration and 24 months of long-term.This indicates that the pellets have good stability and are suitable for long-term storage.The results of pharmacokinetic experiments showed that the peak time Tmax(h)of 1-DNJ controlled release pellets was significantly delayed compared with uncoated pellets,which achieved the purpose and effect of controlled release.1-DNJ controlled release pellets have better sustained release properties than extracts from Folium Mori.The in vivo absorption and in vitro release of 1-DNJ controlled release pellets showed a good correlation.The Tmax delay helps maintain plasma concentration and increases the relative bioavailability of 1-DNJ,which has very important clinical application value. |
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