申请人:Anika Therapeutics Inc.
公开号:EP2656833A1
公开(公告)日:2013-10-30
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-R2-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.
透明质酸(HA)组合物包括交联的、不溶于水的水合透明质酸凝胶颗粒。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。一种增强受试者组织的方法,包括在受试者体内需要增强组织的位置将针头插入受试者体内,其中针头与装有HA组合物的注射器相连,并对注射器施力,将HA组合物送入受试者体内。一种制备 HA 组合物的方法包括形成不溶于水的脱水交联 HA 颗粒,按平均直径分离不溶于水的脱水颗粒,按平均直径选择颗粒子集,用生理上兼容的水溶液水合脱水颗粒子集。另一种制备交联 HA 组合物的方法包括在 pH 缓冲剂存在下用双碳化二亚胺交联交联 HA 的前体,并使交联 HA 脱水。还包括一种在需要增强组织的受试者体内增强组织的方法。一种稳定交联 HA 的方法包括将不溶于水的脱水交联 HA 与包括局麻药的生理相容水溶液水合,其中稳定化组合物的储存模量 G' 值至少是非稳定化组合物 G' 值的约 110%。还包括稳定的 HA 组合物。