Rapid in-situ gel forming compositions prepared via reaction of vinyl sulfone derivatized hyaluronic acid with thiol derivatized polyethylene glycol at alkaline pH

摘要

The present application provides rapid-gelling, sprayable hyaluronic-acid based compositions, kits, related methods, precursor formulations, and uses thereof.

主权项

1. A kit comprising components for preparing a rapid-gelling composition, the kit comprising:
(i) a first container comprising an aqueous solution of vinyl sulfone-derivatized hyaluronic acid (“HA-VS”) at a concentration of from about 10-300 mg/mL, where HA-VS is (2-(vinylsulfonyl)ethoxy)hyaluronic acid, and the HA-VS has from about 11-35% of its hydroxyl groups transformed to 2-(vinylsulfonyl)ethoxy groups, (ii) a second container comprising a thiol-functionalized polyethylene glycol having from 2 to 8 thiol groups, and (iii) a third container comprising a 30-1000 mM buffer solution at a pH ranging from about 8.0-10.5, in an amount effective, when mixed with the contents of the first and second containers, to provide a solution having a HA-VS concentration of 2-8% (w/v) and a thiol-functionalized polyethylene glycol concentration of 2-8% (w/v), wherein the components of the first, second and third containers, when combined, are effective to form a gel within about 10 minutes of mixing.