Development And Evaluation Of Levosalbutamol Sulfate Gels For The Treatment Of Psoriasis

Psoriasis is a chronic autoimmune disease caused by multiple factors.Its clinical manifestations are characterized by erythema and scales,which can occur directly in the patient’s whole body,mostly in the scalp and the extension of the limbs.The incidence of psoriasis is approximately 2% of the population worldwide,and a large number of new psoriasis patients appear each year.The unbearable symptoms and repeated illnesses depress patient’s physically and psychologically.At present,the listed psoriasis treatment drugs are mainly chemical drugs and biologics.The side effects of drugs and the costs are major problems for psoriasis patients.As a short-acting β2 adrenergic receptor agonist,salbutamol is widely used in the treatment of asthma and other respiratory inflammatory diseases.Salbutamol has a chiral structure.Studies have shown that the pharmacological effect of its levorotatory structure is thousand times that of its dextrorotatory structure.The absorption rate of its levorotatory structure in vivo is faster than that of racemates,and its dextrorotatory structure has certain toxicological effect.In this study,R-salbutamol was applied to external preparations for the treatment of psoriasis for the first time,the molding process of R-salbutamol gel was developed,and the quality contant standard and efficacy of the gel were preliminarily evaluated.The main contents of this thesis are as follows:1.Studies on the forming process of R-salbutamol gelsThe single factor experimental method was used to screen the type of R-salbutamol gel matrix.Then,the appearance properties and stability of R-salbutamol gels were investigated by the amount of gel matrix material and the amount of moisturizer,and the formula ratio was optimized.Finally,the basic formula of R-salbutamol gels was determined as follows:35% 2% Carbom U2020,10% 1,2-propylene glycol,0.5% levo-R-salbutamol,54.5% water,p H 6.0±0.2.The molding process was verified and proved to be simple and feasible.2.Studies on the quality standard and stability of R-salbutamol gelsAfter determining the formulation and molding process of the gels agent,HPLC method was adopted to detect the content,related substances,enantiomeric excess(ee)of the R-salbutamol gels,and the detection method was verified.The stability of the influencing factors of R-salbutamol gels was investigated.After 30 days of storage under high temperature and strong light conditions,some indexes of the gels decreased.It shows that R-salbutamol gels should be packaged in a light-proof package and stored undercool condition,so as to meet the requirements of further experiments.3.Studies on the efficacy of R-salbutamol gelsBy constructing IMQ-induced psoriasis-like animal models in mice,to explore the therapeutic effect of R-salbutamol gels on psoriasis.The results of morphological and histological studies show that R-salbutamol gels can improve the skin lesions on the back of mice and reduce the PASI and Baker scores.The result of systemic evaluation of mice showed,R-salbutamol gel can regulate the production of spleen inflammatory immune cells to inhibit the proliferation of spleen cells in mice,which proves the therapeutic effect of R-salbutamol gels on psoriasis.