Preparation Of Cross-linked Sodium Hyaluronate Gels With Different Cross-linking Agents And Research For Its Physicochemical Properties

Hyalouronic acid (HA), a high molecular weight, acidic polysaccharide typically composed of the alternating disaccharide GlcUA(β1-3) GlcNAc. Hydrogel from HA has been widely used in cosmetics, pharmacy and health and beauty industry, such as infusing facial skin to reduce wrinkles and somewhat change the structure and appearance of skins and lips. HA has wonderful biocompatibility,but natural hyaluronic acid is degradable by hyaluronidase (HAase) in vivo. At present, at home and abroad, researches of cross-linking HA gel carried out with different cross-linking agents. The structural reconstruction and modification of natural HA can obtain and its derivative can have better viscoelasticity and enzyme-resistant properties, and maitain the original biocompatibility.The CHA hydrogels were prepared with different cross-linking agents, such as PEG20000, PDE, BDDE, ADH and their mixtures. The optimal reaction conditions were determined by single factor experiment, such as time and temperature of reaction, different conditions of HA, pH, conditions of sterilization, the different ratios of cross-linking agent to HA. he physicochemical properties of four cross-linked sodium hyaluronate gels (CHA) with different cross-linking agents were compared in order to research out the different stability and Enzyme-resistant degradation properties of these CHA gels.The quality of Cross-linked sodium hyaluronate gels were determined by the standard of 《Chinese Pharmacopoeia》(2010), such as Light transmittance, ultraviolet absorption, osmotic pressure, pH, content of ethanol. Content of impurity protein were analysed by Carbazole method. Dynamic viscosity was tested by Stabinger method. Intrinsic viscosity was determined by Uzziah’s viscosity method. The enzyme-resistant degradation properties in vitro of CHA-gels were analysed by carbazole and spectrophotometry.The CHA-gels prepared under optimal reaction conditions have different physical and chemical properties, which set foundation for developing double cross-linked or multifunctional gels with both excellent stability and enzyme-resistant degradation properties.PDE-CHA and PEG20000-CHA gels possess better Dynamic viscosity, PDE-CHA gel has also better intrinsic viscosity, ADH-CHA and BDDE-CHA gels get better Enzyme-resistant degradation properties than PEG20000-CHA and PDE-CHA gels.The CHA-gel with excellent physicochemical properties can be prepared under the optimal conditions, which can set foundation for developing better mechanical and Enzyme-resistant properties products of CHA-gel.