Study On Thymopentin (Tp5) Dry Powder Inhalations For Pulmonary Delivery And Their Pharmacodynamics

Thymopentin (Tp5) is synthesized as an effective part of thymopoietin, which has the ability to take part in the immunological adjustment. It can play a very important role in the treatment of malignant cancer, several kinds of hepatitis and some other infection syndrome. Generally it is given as an injection.Studies on non-injective drug delivery system of polypeptide have been paid much attention to recently. Dry powder inhalations (DPIs) are regarded as useful vector for pulmonary delivery of polypeptides. On the basis of the fuzzy system theory, a complex factor was constructed to unite the dumping ratio, aerosolizing property, bulk density and repose angel to evaluate the qualities of Tp5 DPIs. Meanwhile, the HPLC method was utilized to determine the Tp5 in the DPIs.Studies of the composition and preparation of Tp5 DPIs were emphases of this dissertation. A spray drying method was designed to make the Tp5 DPIs. The formulae were selected according to the complex factor which was constructed in the first part of this dissertation. The manufacture process was selected according to the recovery and the characteristics of the product. For spray-freeze drying method, the ideal preparation conditions were evaluated in the pump spraying speed, the concentration of Tp5 solution and the volume of the solution. Besides, supercritical fluids technology, which was firstly used to powder Tp5, was also studied to make Tp5 DPIs. The preparation process including temperature, pressure, concentration and flow rate of the solution, the co-flow rate of SCF were studied according to the properties of DPIs, and the results were in accordance with the CHP (2000).To detect the biological activity of Tp5 DPIs in vitro, CCK-8 tests were employed. The results showed that Tp5 DPIs had the same biological activity as Tp5 did. The results indicated that carriers without Tp5 had no obvious effect as Tp5 did.Pharmacodynamics study in vivo was executed by giving the Wistar rats Tp5 DPIs periodically, which were injected with immunosuppressant (Cyclophosphamide,...