Impact Of Moist Heat Sterilizafion On The Intrinsic Viscosity And Molecular Weight Of1%Sodium Hyaluronate Injection And Comparative Study Of These Test Methods

The active potent ingredient of sodium hyaluronate injection is sodium hyaluronate (SH), which is one of the main biochemicals existing in human body joint synovial fluid and cartilage matrix. SH in articular cavity exercises lubrication function, can reduce the friction between the organizations, and also play a role of elasticity, buffer the impact of stress on articular cartilage, reduce joint stress, protect articular cartilage from injury.Previously, the domestic manufacturing process of sodium hyaluronate injection mostly is aseptic manufacturing process, and terminal moist heat sterilizing process is rare. With the issues of more strict regulations by SFDA, and the stronger demand of the society for higher safety for injection, more and more domestic manufacturers begin to choose terminal moist heat sterilizing process for sodium hyaluronate injection production, which has become the current trend of the manufacturing process for sodium hyaluronate injection production. SH is a single stranded macromolecule mucopolysaccharides which consists of glucuronic acid unit and glucosamine disaccharides unit repeadly, its molecular weight generally is between hundreds of thousands to millions. Its aqueous solution is non-newtonian fluid, with excellent viscoelasticity, which increases significantly with the rising of solution concentration and molecular weight of SH. However, SH is a heat sensitive material, and prone to thermal degradation. According to reports, the degradation of SH is closely related to the temperature and heat exposure duration, the higher of the temperature and the longer of theexposure time, the more obvious of the degradation of SH. After degradation, SH is decomposed into small molecules polysaccharide, its chemical composition is consistent with that before degradation, being a polysaccharide consisted of disaccharides unit with lower molecular weightandsignificantly decreased viscoelasticity.While the molecular weight and viscoelasticity is the key factors of sodium hyaluronate injection for its clinical effecst. Therefore, sterilizaing parameters should be optimized in its manufacturing process in order to both improve the safety of this product and keep the factors most as possible as we can for its clinical effects.So in this article, sodium hyaluronate injection was prepared by the terminal moist sterilizing process, the influence on its molecular weight and intrinsic viscosity under the different sterilizing parameters was investigated. Meanwhile, different testing methods of molecular weight, shch as GPC, MALLS and intrinsic viscosity reckoning method were studied and compared. The main work is as follows:1. SH with different molecular weight were choosed to prepare the pre-test samples of the injection, which were sterilizated by different parameters. Test the molecular weight (Mw) and molecular weight distribution by GPC, MALLS, meanwhile, test the Mv by intrinsic viscosity test to every samples made by different sterilizing parameters to study the influence of the temperature and exposure time on sodium hyaluronate injection with different molecular weight preliminarily.2. Samples of laboratory and pilot lot scale were prepared to further investigate the influence of the temperature and exposure time on the Mw of sodium hyaluronate injection.3. Three methods of Mr tests, MALLS, GPC and intrinsic viscosity method, were used to test the Mw of sodium hyaluronate injection, and data from three methods were compared to figure out which method is more applicable.