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Crosslinked hyaluronic acid compositions for tissue augmentation

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.
Owner:ANIKA THERAPEUTICS INC
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