| Ulcerative colitis(UC)is a chronic non-specific intestinal inflammatory disease.It brings great pain to patients’ work and life.UC can be attributed to traditional Chinese medicine.Gegenqinliantang(GGQLT)is derived from the classic ancient recipe Treatise on Febrile Diseases.It is a traditional Chinese medicine decoction commonly used in clinical treatment of damp-heat intrinsic ulcerative colitis.After years of clinical trials,the effect is significant.The main clinical method is oral administration.and enema treatment.However,the administration of enema treatment is inconvenient and the side effects are large.And the oral administration of drugs is easily absorbed in the stomach and small intestine causing a low treating efficience.In this project,the traditional Gegenqinlian formula is simplified,and the suitability of this simple formula in the treatment of ulcerative colitis is investigated through pharmacodynamic experiments.Based on this,a berberine hydrochloride-nanoparticles of Gegenqinlian Colon-Specific Capsules to overcome the disadvantages of traditional Gegenqinliantang in treating ulcerative colitis.Objective: To develop a novel Gegenqinlian dosage form which can improve the compliance of patients and realize the specific release of the active ingredients of the drug in the colon,and at the same time improve the therapeutic effect of the anti-inflammatory active ingredient Berberine hydrochloride in colon.Methods:(1)Establish a quantitative method for uplc in vitro analysis of Gegen Qinlian Jianfang Colonic Capsules,and simultaneously determine the content of the active ingredients puerarin,baicalin,and berberine hydrochloride in Gegen Qinlian.(2)Preparation of berberine hydrochloride sodium alginate-chitosan nanoparticles by ion crosslinking method.Zeta potential,encapsulation rate,and drug loading were used as indicators of investigation,and the optimal prescription was obtained.FTIR and DSC were used to characterize the nanoparticles.(3)The effective components of Gegen Qinlian formula were extracted to prepare the colon soluble capsule of Gegen Qinlian formula,and the nanoparticles were put into the capsule together with other components of the formula to prepare the colon soluble capsule of Gegen Qinlian formula with berberine nanoparticles.And its release characteristics were verified by in vitro release experiments.(4)Through a SD rat model of ulcerative colitis,observe clinical activity,DAI score,CMDI score,determine colon length,spleen index,thymus index and colon index,and compare the treatment of Gegenqinlianfang and Gegenqinlianjianfang.A shireneiyun ulcerative colitis rat model was used to determine the colon length,spleen index,thymus index,and colon index based on clinical activity observations,DAI scores,CMDI scores,and traditional decoctions.The therapeutic effect of Gegenqinlian colon-specific Capsules and Gegenqinlian colon-specific Capsules containing berberine nanoparticles.Results:(1)The established in vitro UPLC quantitative analysis method of Gegenqinlian is simple,accurate and reliable.Under the selected chromatographic conditions,the three major substances in Gegenqinlian have good resolution and good peak shape.(2)The optimal process conditions for berberine hydrochloride chitosan-sodium alginate nanoparticles is pH = 4.0,speed 400 rpm,reaction time 40min;the optimal prescription is: SA 0.4 mg/m L,CS 0.5 mg/m L,Crosslinking agent sodium tripolyphosphate concentration is 0.5mol/L,p H is 4.0,berberine hydrochloride dosage is 0.5 mg / m L.The prepared nanoparticle has a drug loading rate of 12.4 ±0.016% and an encapsulation rate of 83.6 ± 0.155.%,Particle size is about 250 nm,Zsta potential is-30 m V ± 0.143.(3)In vitro release experiments have demonstrated the colon-localized release effect of Gegenqinlian Jianfang Colon Capsule Capsules and berberine nanoparticle-containing Gegenqinlian Colon Capsule Capsules,and the nanoparticles were also released from the capsules as a prototype.(4)Pharmacodynamic results show that Gegenqinlian Quanfang and Jianfang can Jianfang alleviate the clinical symptoms of ulcerative colitis rats to a certain extent and reduce the DAI score.There is no statistical difference in the treatment effect between the two dosage.A rat model of shireneiyun ulcerative colitis was prepared by combining diet induction with TNBS.The pharmacodynamic results showed that the treatment group could alleviate the clinical symptoms of shireneiyun UC rats and reduce the DAI score after one week of administration.CMDI score,increase the length of the colon decrease the weight of the colon and spleen and increase the weight of the thymus,which is significantly different from the model group.Among them,the Gegenqinlian Jianfang Colonic Capsule was better than traditional Gegen Qinlian decoction in treating UC.Based on this,the treatment effect of berberine-loaded nanoparticles Gegenqinlian Jianfang Colonic Capsules is more significant.Conclusion: The berberine-loaded nanoparticles Gegenqinlian Colon-specific Capsules,which improve the patient’s compliance,realize the colon-localized release of the active ingredients in Gegenqinlian formula.The design of nano-carriers has improved its ability to resist ulcerative colitis.It lays a solid experimental foundation for the traditional Chinese medicine compound preparation in the nano drug delivery system. |
PDF Full Text Request