不同分子量配比交联透明质酸钠凝胶皮下注射的动物及临床实验  

Crosslinking sodium hyaluronate gel with different ratio of molecular weight for subcutaneous injection： animal experimental study and clinical trials subcutaneous injection

作　　者：冉维志[1] 王晓丽[1] 胡月飞[1] 高崧瀛[1] 杨亚红[1] 孙健[1] 孙淑明[1] 刘忠梅[1] 王姜玲 

机构地区：[1]黑龙江省医院,哈尔滨150036

出　　处：《中华整形外科杂志》2015年第3期198-201,共4页Chinese Journal of Plastic Surgery

摘　　要：目的 观察不同分子量透明质酸钠凝胶的生物相容性及体内、外的降解速率,以获取维持注射填充美容效果时间较持久,并最终可完全降解的、安全有效且成本较低的注射用美容填充剂.方法 ①在碱性条件下,选择分子量分别为4×105、8×105、10×105、12×105的透明质酸钠与二乙烯基砜交联配制胶体;②筛选健康昆明小鼠,随机分成透明质酸凝胶组（A组）和透明质酸原液组（B组）,A、B组再各均分为3小组,每小组背部皮下注射不同分子量透明质酸钠凝胶或透明质酸钠原液,并于注射后7、90、180 d,观察其在动物体内的生物相容性及降解速率,同时将不同分子量的透明质酸钠凝胶在密封低温及空气中分别静置,观察其自然降解速率.③筛选出降解速率最稳定胶体,将其在后期召集的志愿者中行面部美容注射,观察注射效果及降解速率.结果 分子量为4×105的透明质酸钠凝胶在90 d时降解完毕,分子量为8×105的透明质酸钠凝胶在180 d时降解完毕,分子量为10×105的透明质酸钠凝胶在180 d时降解至90.0％;原液均可在7d内完全降解吸收;体外密封低温保存12个月,其胶体状态无明显变化,在空气中静置1d胶体完全降解;分子量为10×105的透明质酸钠凝胶动物及临床试验中其注射效果可以保持6个月以上.结论 在物料比相同的情况下,分子量越低的透明质酸钠凝胶降解速率越高,分子量越高的透明质酸钠凝胶降解速率越低,但分子量过大的透明质酸钠凝胶无法形成良好流动性的胶体;故分子量为10×105的透明质酸钠凝胶在临床注射中应为首选.Objective To investigate the biocompatibility and degradation rate of crosslinking sodium hyaluronate gel with different ratio of molecular weight,so as to choose the effective,safe and totally degraded hyaluronate gel for aesthetic injection.Methods ①Compound colloid was formed by cross-linking the divinyl sulphone and sodium hyaluronate with different molecular weight （4 × 105,8 × 105,10 × 105,12 × 105）.②Healthy level KM mice was randomly divided into two groups to receive hyaluronic acid gel or liquid injection.Each group was subdivided into three subgroup to receive hyaluronic acid with different molecular weight.The biocompatibility and degradation rate,of hyaluronate were observed at 7,90,180 days after injection.At the same time,different molecular weight of sodium hyaluronate gel is sealed or exposed respectively under the low temperature preservation to observe its natural degradation rate.③The most stable colloid was selected as aesthetic injector for volunteers to observe the aesthetic effect.Results The sodium hyaluronate gel with molecular of 4 × 105 was completely degraded 90 days later.The sodium hyaluronate gel with molecular of 8 × 105 was completely degraded 180 days later.The sodium hyaluronate gel with molecular of 10 × l05 was degraded to 90.0％ after 180 days.The sodium hyaluronate liquid can be degraded completely within 7 days.The colloid could be kept for at least 12 months when sealed under low temperature,but was totally degraded when exposed for 1 d.Sodium hyaluronate gel with molecular 10 × 105 was confirmed to be kept for at least 6 months in animal experiment and clinical trials.Conclusions Under the same condition of material ratio,the higher the molecular weight is,the lower the degradation rate is.But the liquidity of gel is not good for injection when molecular weight is too large.It suggests that Sodium hyaluronate gel with molecular 10 × 105 maybe the best choice in cosmetic injections.

关 键 词：透明质酸 二乙烯基砜 材料试验 

分 类 号：R318.08[医药卫生—生物医学工程]