申请人:Sadozai K. Khalid
公开号:US20050136122A1
公开(公告)日:2005-06-23
A hyaluronic acid (HA) composition includes crosslinked, water-insoluble, hydrated HA gel particles. The HA includes crosslinks represented by the following structural formula:
HA—U—R
2
—U—HA
The variables are defined herein. A method of augmenting tissue in a subject includes inserting a needle into a subject at a location in the subject that is in need of tissue augmentation, wherein the needle is coupled to a syringe loaded with the HA composition, and applying force to the syringe, to deliver the HA composition into the subject. A method of preparing the HA composition, includes forming water-insoluble, dehydrated crosslinked HA particles, separating the water-insoluble, dehydrated particles by average diameter, selecting a subset of particles by average diameter, and hydrating the subset of dehydrated particles with a physiologically compatible aqueous solution. Another method of preparing the crosslinked HA composition includes crosslinking a precursor of the crosslinked HA with a biscarbodiimide in the presence of a pH buffer and dehydrating the crosslinked HA. Also included is a method of augmenting tissue in a subject that is in need of tissue augmentation. A method of stabilizing crosslinked HA includes hydrating water-insoluble, dehydrated crosslinked HA with a physiologically compatible aqueous solution that includes a local anesthetic, wherein the value of storage modulus G′ for the stabilized composition is at least about 110% of the value of G′ for a non-stabilized composition,. Also included is the stabilized HA composition.
一种透明质酸(HA)组合物包括交联的、不溶于水的、水合的HA凝胶颗粒。HA包括由以下结构式表示的交联:HA—U—R2—U—HA。变量在此定义。一种在受试者中增强组织的方法包括将针插入受试者体内需要组织增强的位置,其中针连接到装有HA组合物的注射器,并施加力量到注射器,将HA组合物注入受试者体内。一种制备HA组合物的方法包括形成不溶于水的、脱水的交联HA颗粒,通过平均直径分离不溶于水的、脱水的颗粒,通过平均直径选择颗粒的子集,并用生理兼容的水溶液使脱水的颗粒子集水化。另一种制备交联HA组合物的方法包括在pH缓冲剂存在下用双异氰酸酯交联交联HA的前体,并脱水交联HA。还包括一种在需要组织增强的受试者中增强组织的方法。一种稳定交联HA的方法包括用含有局部麻醉剂的生理兼容水溶液水化不溶于水的、脱水的交联HA,其中稳定组合物的存储模量G′的值至少为非稳定组合物G′值的约110%。还包括稳定的HA组合物。