Study Of The Thymopentin Inhalation

Thymopentin (TP5) is a synthetic oligopeptide, protein structure thymus immunoreactivitycenter with the same pixel generates all thymus physiological function, which can regulate theimmune system to produce a two-way effect. TP5is currently mainly used in the clinical treatmentof immunocompromised due to a variety of causes, including cancer, chronic hepatitis B, chronichepatitis C and hepatitis biliary tract infections, multiple drug-resistant tuberculosis resistant tumortype leprosy, sepsis complications, such as severe burns, but also the treatment of diabetesautoimmune disorders, menopausal syndrome, improve immune function, such as the frail elderly.Dry powder inhalation is a kind of pulmonary administration system. It means one or moredrugs were delivered into the respiratory tract through a special device as a special form of drypowder, functioning at system or local sites. It is efficient, quick and small side effects. At present,developing safe, effective, high bioavailability of non-injection protein or peptide drugs is one of thehot issues in pharmaceutics. Pulmonary delivery system cannot only avoid the first pass and thegastrointestinal degradation, but also absorb the drug through pulmonary alveolar cells. the huge,beneficial biological drug delivery has advantages and can improve the bioavailability.Theoretical studies of lung deposition confirmed that during inhalation, the position of theirdeposition is closely concerns to the particle size. Particle size is generally considered>10μmparticles deposited in the oropharynx,>5μm deposited in the bronchi,<3μm deposited in the alveolisite,<0.5μm with the breath is expelled. So to get a good suction efficiency of inhalation must beprepared to micron-sized particles. Upcoming micronized drugs and carriers. And a dry powderinhaler peptide drugs in the process of focus "micronized", only the reduced particle size of thepowder by speaking an appropriate range, it may be advantages of pulmonary delivery system toachieve the administration.In this study, Thymopentin was used as a model drug to study the formulation and preparationprocess of Thymopentin dry powder inhaler, doing detailed examination of the Thymopentin drypowder inhaler in the preparation process, the role of the different components of the prescriptionand different processes affect the condition of the product, to discuss changes in the amplificationfactor of dry powder inhaler preparation, and the product prepared in pharmacodynamicscharacteristics of rats were studied. A dry powder inhaler comprising a plurality of evaluation indexes, such as: particle morphology,tap density, angle of repose, emptying vitro deposition rate. In this paper, particle size is the mainindicators, supplemented by visual observation, the use of mathematical methods, will unify fourdifferent dimensionless index is a dimensionless complex evaluation index, this index as a drypowder inhaler based on the physical performance evaluation to avoid Since each index betweendifferent standards and thus the impact of carrier screening system. In addition, the establishment ofThymopentin content by HPLC preparation, good specificity of the method in the0.04mg/mL~0.3mg/mL concentration range, a good linear relationship between concentration and peak area TP5,the regression equation is A=(7E+6) x-20425, r=0.9994. Accuracy and repeatability of the methodwere good, recovery test and precision study are in line with regulations. Sample solution can beincubated at room temperature12h, for in vitro evaluation method for measuring the content of TP5.In addition to Thymopentin stability study conducted prior to preparation.The second part is the main work on the preparation process and the dry powder inhalerformulation is studied. This article uses a technique commonly used in powder-powder prepared byspray drying. According to the characteristics of dry powder inhaler design the correspondingprescription and technology, the use of composite evaluation of the vector system were screened, anddesigned orthogonal experiment investigated the impact of technological factors on the yield andtraits to achieve different effects on integrated optimization factors. Optimized Thymopentin drypowder inhaler good preparation process stability can be achieved on a level suitable for inhaledparticle size, and good mobility, good atomization. Capsule filling the2nd item, the loading onTurbospin inhaler, using a new generation of European Pharmacopoeia was evaluatedpharmaceutically impactor results prove that the product can be prepared to achieve betteraerodynamic diameter and the deposition rate in vitro. Optimized conditions for: A2B2C1, namelyventilation0.5m3/min, atomization pressure3.0bar, inlet temperature of130℃. Using the preferredprocess for preparing batches of prescription and dry powder, for process validation, the results showthe optimized process for preparing dry powder products TP5good nature, process stability.After making the prescription and technology research, the paper went on during the preparationof dry powder inhaler conducted a preliminary exploration, and factors may arise conducted apreliminary study of the amplification process. In previous studies, although there are a lot of drypowder inhaler literature reports, but generally dry preparation laboratory scale and industrialproduction is still out, the most critical issue is the process used in mass production and laboratoryscale similarity process. This chapter discusses the equipment under conditions of constantadaptation of the process, the results prove that the product is more stable preparation process. The next step for the stability of the product conducted a preliminary study, the main factorswere investigated to test the changes in the powder-filled capsules, the high temperature, highhumidity and light conditions placed occurred. The results showed that dry powder inhalation filledin gelatin capsules capsule causes water absorption, internal powder compaction, the use of HPMCcapsules can ensure that the internal nature of the powder is too large change does not occur. In thehigh-temperature, high humidity and light three factors, the influence of humidity on the largest drugmay cause compaction, thus affecting the emptying and suction performance; temperature was lessaffected, there may be a small amount of degradation problems; illumination of the powder is Noexcessive influence. So in storage, good sealing packaging material suitable choice in a cool, dryplace.Finally, the product was prepared in vivo pharmacodynamics experiments. According to theaction principle of thymopentin, the immunosuppression rats were given by the dry powder inhalerof thymopentin, measured in peripheral blood cells CD4+, CD8+ratio of the number of cells andcompared to the CD4+/CD8+ratio value, then the effects of thymopentin can be evaluated. Theresults showed that the inhalation of thymopentin has a similar function comparing to the injectionwhich can improve CD4+/CD8+values. The thymopentin can be absorbed into the bloodstreamthrough the lungs.The results of this study showed that it is feasible to deliver peptide drugs through lungabsorption route but the absorption mechanism needs further exploration. However, its marketprospects a lot with high value application development.