Studies On The Synthesis Of Metal-based Drugs Of Tiopronin And Their Treatments For Hepatitis

Hepatitis is caused by the inflammation of liver. It’s a kind of liver inflammation diseasewith the symptom of injured liver and hepatic dysfunction. The therapy of hepatitis has alwaysbeen a serious clinical problem. Tiopronin is a new drug, which has been widely used in clinicas the medicine for improving liver function. It can effectively cure chronic hepatitis, alcoholichepatitis and other relevant symptoms. It can protect hepatic cells and be taken as protectingagents of the radiotherapy and chemotherapy and be used as the antidote of heavy mental.Tiopronin was a strong acid.(pH1.6). It was used in clinic together with sodium carbonate.However, it has been discovered that tiopronin is easily decomposed in buffer solution whenneutralized by soudium carbonate. It is also reported that tiopronin has cause some adversereaction in many clinical cases, such as allergy, nausea, chest tightness, parotid gland swellingand even shock. So it still remains a clinical problem that tiopronin can be easily decomposedin the process of neutralization, which may influence curative effects. But due the difficultsynthestic process, no appropriate sodium tiopronium was put into use.On the basis of structue of tiopronin, we design and synthesize metal-based tiopronin durgsfor clinical use. Sodium, potassium and zinc are essential trace elements for human body,which have an important biological function. We use chemical methods to combine tioproninwith sodium, potassium and zinc, to prepare salts and organometallic compounds. Accordingto the pharmacology function of matrix and metal, collaborative therapy is achieved andtoxicity is reduced. It have been reported that sodium tiopronin hydrate can be prepared by2-ethyl hexanol sodium and tiopronin in isobutanol solution, then the product is separated byadding water. However, this method has disadvantages of lower yields and complex operation.We mainly find the processes for preparing sodium tiopronin, potassium tiopronin and zinctiopronin. These new methods have the higher yields, better products, simpler operation, lowercost and can be simply put into industrial operation. And the research of pharmacology andtoxicology indicated that comparing with tiopronin, modified sodium tiopronin, potassiumtiopronin and zinc tiopronin have better stability and low side-effect in clinic.Through the determination of its physical and chemical constants, organic analysis,1H-NMR,13C-NMR,Mass Spectrum (MS), Infrared Spectrum (IR), Ultra Spectrum (UV), power X-ray Diffraction(XRD), et al., the structure of metal-based drug of MPG is verified.The pharmacology and toxicology of sodium tiopronin were studied. We then carry on thecomprehensive analysis of sodium tiopronin for clinical use. We manage to make crude druginto injections, tablets and capsules. Because of the similar pharmacological effects of sodiumtiopronin and tiopronin, we prepared enteric-coated tablets, which are coated by anti-acid film.We have tried different formulations, made a study of release percent and dissolution percentof the tablets and finally optimized the radio. We make a further study of quality research todetermine the quality of NaMPG tablets and have set feasible quality standard.According to the requirement of SFDA, we have accomplished the research of NaMPGcombining its preparation process and quality research. Now we have get Chinese NewMedicine Certificate and Product License of NaMPG. and its injections. We have applied forChinese patent of invention and successfully get authorized.At present, we are doing all kinds of research of zinc tiopronin and potassium tiopronin tocollective scientific data. We will apply for the Chinese new medicine certificate of zinctiopronin and potassium tiopronin and try to develop new drugs for hepatic disease.