Study On The Multidrug Crystal With Metformin As API And Preperation Of Rosiglitazone Derivatives

Diabetes is a disease caused by a variety of factors,which mainly characterized with high blood glucose.And 90% patients have type 2 diabetes.Additionally,this disease is a chronic disease.The patients need to take medicine for life.It's dangerous to patients' organs and tissues with long-term high blood glucose.And then,these will cause systemic complications.Therefore,we are responsible for preventing of diabetes and its complications and saving the life of diabetes patients.Co-crystal preparation technology can connect two or more molecules into supramolecular structures through non-covalent bonds.And this tech can improve the physicochemical properties and pharmacological activities of the raw active pharmaceutical ingredients.Metformin,known as a modern "miracle drug",mainly has effect on controlling glucose and anti-cancer by the AMPK signaling pathway.Moreover,this compound has moderate size and multiple hydrogen bonding sites.So these advantages make it become the best choice for co-crystal drugs.In this article,metformin was selected as active pharmaceutical ingredient.Several medicines with different mechanism will form multidrug crystals with metformin,such as glimepiride,fluorouracil and berberine.And then,these multidrug crystals' structures were characterized by thermal analysis,infrared spectroscopy and X-ray powder diffraction.It is expected to improve their physicochemical properties or enhance their pharmacological activity by supramolecular co-crystal technology.Interestingly,glymepiride-metformin multidrug crystal has a sandwich two-dimensional molecular structure by X-ray single crystal diffraction.It provides a new strategy for solving the problem of solubility and hygroscopicity of the raw material at the same time.In addition,glymepiride-metformin has superior pharmacological effcet both on controlling glucose and anti-cancer than one of pure components.We also modified the structure of rosiglitazone.The target of the compound is PPAR? receptor.Studies have shown that the N-H structure of thiazolidinedione ring is an indispensable active group of rosiglitazone,and the drug does not need to activate PPAR ? completely to achieve the corresponding hypoglycemic effect.Therefore,rosiglitazone can be transformed from a full agonist to a partial agonist by structural modification on the N-H bond of the 2,4-thiazolidinedione group.Then,it's expected to obtain a series of novel compounds with similar activity to rosiglitazone but with reduced side effects.So far,10 derivatives have been synthesized and characterized by high performance liquid chromatography,nuclear magnetic resonance spectroscopy and infrared spectroscopy.