Patent ID: 11857682
Assignee: AMC
Field: Pharmaceuticals (Chemistry)
Classification: CPC A | IPC A

Claim 0:
1. A method of making a modified hyaluronate composition, comprising
providing an aqueous solution of uncrosslinked hyaluronic acid or uncrosslinked sodium hyaluronate in unbuffered 135 mM to 200 mM NaCl, wherein the uncrosslinked hyaluronic acid or uncrosslinked sodium hyaluronate has a weight averaged molecular weight from 500-2000 kDa, and wherein the aqueous solution includes no phosphates,
crosslinking the uncrosslinked hyaluronic acid or uncrosslinked sodium hyaluronate in the aqueous solution with a dialdehyde or disulfide crosslinking agent to provide crude modified hyaluronate having a soluble fraction and a crosslinked fraction with a 10% to 98% degree of crosslinking, wherein the soluble fraction comprises less than 4% by weight of hyaluronate having a molecular weight less than 250 kDa based on the weight of the hyaluronate,
centrifuging the crude modified hyaluronate and removing at least a portion of the soluble fraction, and
optionally repeating the centrifuging and removing until the modified hyaluronate has less than 10% by weight of the soluble fraction based on the total weight of hyaluronate, with a soluble fraction polydispersity (Mw/Mn) of 1 to 1.6, an Rh of the crosslinked fraction of 150 nm to 2000 nm, and an Rz of the crosslinked fraction of 50 nm to 700 nm, wherein Rh>Rz.