| Scutellariae radix comes from the dried root of Scutellaria baicalensis Georgi,which is a traditional Chinese medicine and widely used in China.It has the effects of clearing away heat and dampness,purging fire and detoxifying,hemostasis and relieving fetus.Baicalin is its main active ingredient and has the anti-pyretic,anti-inflammatory,anti-tumor,antioxidant and other pharmacological effects.At present,the baicalin added in the preparation is prepared according to the extraction process of baicalin in the Chinese Pharmacopoeia,which is water extracting-alcohol precipitating,alkali-solution and acid-isolation.But baicalin has poor water solubility and low bioavailability,which limits its clinical application.A large number of literature reported that it can improve the dissolution and bioavailability of baicalin by formulation technology,however,the preparation technology has limited improvement in the dissolution of baicalin.The research team found earlier that the original form of baicalin in plants is the baicalin magnesium salt.Baicalin magnesium salt is easily soluble in water,and baicalin magnesium salt can be obtained by neutralization reaction using baicalin as raw material.Bacteriostatic tests shoued: baicalin magnesium salt had inhibition on Staphylococcus aureus,Escherichia coli,and Pseudomonas aeruginosa to different degrees,and all were significantly superior to baicalin.It could significantly reduce the acute liver injury caused by carbon tetrachloride in rats by intravenous administration of baicalin magnesium salt saltfreeze-dried powder.It has a good application prospect that development of baicalin magnesium salt as injection.It was found that the acidic environment would destroy the form of baicalin magnesium salt early.In order to avoid the influence of gastric acid in this experiment,the baicalin magnesium salt was prepared as an enteric preparation and pharmacokinetic characteristics in vivo was investigated compared with baicalin enteric preparation.Based on the fact that the baicalin magnesium salt is easily soluble in water,dissolution is no longer the main problem limiting the absorption of baicalin magnesium salt in vivo,and the membrane permeability may have a greater impact on the absorption of baicalin magnesium salt.A large number of literature reported that combination of drugs and phospholipids can effectively improve the permeability of the drugs.In order to promote the absorption of baicalin magnesium salt in the small intestine,this experiment attempts to prepare baicalin magnesium salt into phospholipid complex,and characterize it and determine the physical and chemical properties of complex.The unidirectional intestinal perfusion in rats was used as the experimental model to investigate the absorption of the compound in the small intestine,which provided a basis for the subsequent development of enteric-coated preparations of baicalin magnesium salt phospholipid complex and provided a reference for the application of oral administration of baicalin magnesium salt.Objectives:Prepare the enteric-coated granules of baicalin magnesium salt,and investigate their pharmacokinetic characteristic.Optimize the preparation process of baicalin magnesium salt phospholipid complex,and investigate its physical and chemical properties.Explore the absorption of phospholipid complex in the small intestine,which provide a reference for the development of oral preparations of baicalin magnesium salt.Methods:1.Optimized the preparation process of the granular inner core by the orthogonal design.Eudragit L30D-55 was used for enteric coating.The cumulative release of enteric-coated granules was investigated in acid and base in vitro.The analysis method of baicalin magnesium salt in vivo was established by HPLC.The pharmacokinetic characteristic of enteric-coated granules were investigated in rats by oral administration.2.Prepared the baicalin magnesium salt phospholipid complex by the solvent method with the index of compounding rate.Based on the single factor investigation,orthogonal design was used to optimize the preparation conditions and determine the best preparation process.The properties of the complex were investigated by XRD,DSC,FTIR and SEM.The fat solubility of the complex was investigated by oil-water partition coefficien.3.Investigated the absorption of baicalin magnesium salt phospholipid complex in the small intestine by the model of rat single-pass intestinal perfusion test with the evaluation indicators of Ka and Papp values.Results:1.The cumulative release rate of the baicalin magnesium salt enteric-coated granules was(4.12±0.62)% in 0.1 mol/L hydrochloric acid solution for 2 h,and(99.33±1.11)% in buffer of p H 6.8 for 2 h.The analysis method of baicalin magnesium salt in vivo established by HPLC was simple and accurate,which was suitable for the analysis of baicalin magnesium salt.The pharmacokinetic results were that the Cmax of baicalin magnesium salt enteric-coated granules was(0.80±0.49)mg·L-1,and the AUC0?t(20.23±4.89)mg·L-1·h,and the Cmax and AUC0?t of baicalin enteric-coated granules were(1.16±0.38)mg·L-1 and(22.59±3.88)mg·L-1·h,respectively,which showed that there was no statistical difference between the enteric-coated granules of baicalin magnesium salt and baicalin.2.The optimal preparation conditions of baicalin magnesium salt phospholipid complex were as follows: the reaction solvent was ethyl acetate:methanol(9:1),the drug-lipid ratio was 1:1.5,the reaction concentration was 2 mg/m L,and the reaction temperature was 55 °C.The complexing rate was(89.8±1.7)%.The characterization results showed that there was an interaction between the baicalin magnesium salt and the phospholipid molecule,and the two formed a complex.The oil-water partition coefficient of the complex has increased.3.The Ka and Papp of the complex in the small intestine were(0.438±0.068)h-1 and(0.0755±0.028)cm·h-1,which were significantly improved compared with the baicalin magnesium salt.Conclusions:1.Enteric-coated granules that can transmit most of baicalin magnesium salt to the small intestine and release can be prepared with the inner core that optimized by the orthogonal design and with the enteric coating of Eudragit L30D-55.The pharmacokinetic characteristics of baicalin magnesium salt enteric-coated granules are not statistically different from baicalin enteric-coated granules.2.Baicalin magnesium salt phospholipid complex can be obtained by solvent method with a high compounding rate,and the fat solubility of the complex is improved.3.Preparation of baicalin magnesium salt into phospholipid complex can improve its absorption in the small intestine significantly. |
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