Preparation Of Compound Liposome Thermosensitive Gel For Ulcerative Colitis And Its Drug Release Study In Vitro

Ulcerative colitis(UC),also known as chronic non-specific ulcerative colitis,is a chronic inflammatory bowel disease involving the rectum and colon mucosa.The clinical cure rate is low,and is closely related to the occurrence of colon cancer,the patients' health and life is endangered.UC has been listed as one of the modern refractory cure disease by WHO.UC is classified as Chinese medicine "dysentery" "diarrhea" category,spleen deficiency and dampness hysteresis is the pathogenesis.So clinical treatment emphasizes the spleen and replenishing Qi,heat-clearing and dampness.Licorice is better for spleen replenishing Qi,heat-clearing and detoxification effect,and its effective components named diammonium glycyrrhizinate(DG)has strong of non-specific anti-inflammatory,anti-allergy and the immune regulation effect;Sophora flavescens is good for heat-clearing and expelling dampness common medicine,its effective components named matrine(MT)has anti-inflammatory,antibacterial,and other pharmacological activity.Combination of the two,in line with the traditional Chinese medicine clinical therapeutic treatment of UC,reflects the traditional Chinese medicine "drug" advantage of compatibility.There are many disadvantages in traditional rectal drug delivery,such as poor compliance and short residence time.Therefore through this study of DG-MT compound liposome thermo-sensitive gel(DM-Lip-TSG),combined with the advantages of liposomes and thermo-sensitive gels as drug carriers,in order to study an efficient and safe rectal administration new formulations,to provide the theoretical basis for the clinical treatment of ulcerative colitis.Firstly,DM-Lip prescription research before.HPLC method was established to determine DG and MT,and method validation.The solubility of DG in different solvents was investigated,and the oil-water partition coefficient of MT was investigated by Shake-flask method.To provide the basis for the preparation methods of DM-Lip.Secondly,To screen the preparation of DM-Lip-TSG and its optimal prescription.According to the results of preliminary experiment,DM-Lip was prepared by reverse evaporation method.The Box-Behnken effect surface method was optimized for the prescription and process by taking the combined effect of DG and MT encapsulation efficiency of overall desirability(OD)as the index.The best prescription and preparation were verified,and the stability of DM-Lip was investigated.With the optimization of matrix formulation of thermo-sensitive gel by the same method and preparation of DM-Lip-TSG.Thirdly,To screen out the natural adhesives of Rhizoma Bletillae polysaccharides for the thermosensitive gel adhesion agent.According to many experiments,the Rhizoma Bletillae polysaccharides was determined to be a thermosensitive gel tackifier,and the adhesion between Rhizoma Bletillae polysaccharides and hydroxypropyl methyl cellulose(HPMC)was compared,the results showed that the polysaccharide had good adhesion,and biodegradable,safe without stimulation.While it has a good anti ulcer,hemostatic pharmacological action,play a "drug-assisted dual-use" good purposes.Fourthly,To evaluate the quality of the compound lipid thermosensitive gel.The stability,safety and residence time of DM-Lip-TSG were investigated.The results showed that the stability of DM-Lip-TSG was good and there was no obvious irritation.The average residence time of DG and MT in DM-Lip-TSG was 1.21 times and 1.14 times of ordinary gel.Finally,Design of quantitative rectal delivery gun.Combined with the characteristics of DM-Lip-TSG,a rectal quantitative feeding gun was designed,the intervention performance is better,it's easy to control the dose of the drug,and can accurately reach the pathological changes of the rectum,improving drug comfort,easy to use,the application prospect is broad.This study combined with traditional Chinese medicine "drug",preparation of compound liposomes,while the choice of natural adhesives Bletilla polysaccharide for thermo-sensitive gel tackifier,also the repair of mucosal ulcer,played "drug-assisted dual-use" role.The compound liposome thermosensitive gel has better drug release characteristics,and design of rectal quantitative gun,so as to facilitate the patients to self medication.The results showed that the preparation had good stability,no irritation to rectal mucosa and better drug release performance,which is expected to improve the therapeutic effect.Therefore,this study provides a theoretical basis for subsequent rectal cavity drug delivery research.