Preparation Of A Medical Cross-linked Sodium Hyaluronate Gel

Hyaluronic acid is a natural polysaccharide composed of D-glucuronic acid and N-acetyl glucosamine.It is widely used in clinical medicine,plastic surgery beauty and cosmetics,such as viscoelastic ophthalmic surgery,surgical adhesions barrier,injectable dermal fillers,and cosmetic additives.However,it is easy to be degraded by hyaluronidase,which is distributed in human body.Therefore,it is necessfuy to modify its structure with chemical agent so as to make better use.In this study,sodium hyaluronate gel was prepared by chemical crosslinkiong,the degradation time of the gel was lengthened.Furthermore,a suitable method for scaling-up was provided for preparation of cross-linked sodium hyaluronate gel.Analysis showed that the product met the Pharmaceutical Industry Standard of the People's Republic of China,"The Medical Cross-linked Sodium Hyaluronate Gel(YY0308)".1,4-Butanediol diglycidyl ether was used to crosslink sodium hyaluronate.Influencing factors of temperature,time and the concentration on the reaction were studied,and the optimized conditions were determined as followings:reaction temperature at 40?,reaction time for 4 hours,1%concentration of sodium hyaluronate.Among three approaches of preparing the cross-linked sodium hyaluronate gel,emulsification method was the best one suitable for scaling-up in producing.The preparation conditions are investigated and deterlined as followings:reaction temperature at 400C,5%concentration of emulsifier,emulsification time for 15min,stirring rate at 12 00r/min.At the final stage,the residual cross-linker was removed by steaming at 126? for 20min.Quality analysis was performed in line with the standard of Chinese Pharmacopoeia(2010),and the result was listed as followings:light transmittance 99.7-99.9%,ultraviolet absorption 0.3-0.4,pH 6.9-7.2,osmotic pressure 300-315 mOsmol/L,heavy metal content 3-7?g/g.At the same time,many other properties were measured:swelling degree 19,particle size 110-300?m,sodium hyaluronate content 18.35mg/ml,protein residues 0.0805%,residues of the crosslinking agent 1.122?g/g,and the degradation time above eight months.