Injectable monophase hydrogels
An injectable monophase hydrogel is provided that is made of a reaction mixture of hyaluronic acids having different molecular weights.
1. An injectable hydrogel useful in preventing tissue adhesion, the hydrogel made by a process comprising the steps of: 1) forming a mixture of a first hyaluronic acid salt product having a first molecular weight and a second hyaluronic acid salt product having a second molecular weight greater than the first molecular weight, wherein the first hyaluronic acid salt product and the second hyaluronic acid salt product are two separate pre-existing products prior to the forming step, wherein the mixture contains about 90% by weight of the first hyaluronic acid salt product and about 10% by weight of the second hyaluronic acid salt product, wherein the first hyaluronic acid salt product is a sodium salt having a molecular weight of about 3×10 5 Da, and the second hyaluronic acid salt product is a sodium salt having a molecular weight of about 3×10 6 Da; 2) cross-linking the mixture of step 1 ) in an aqueous solvent in the presence of an effective and non-excessive amount of at least one cross-linking agent, such that the degree of cross-linking, defined by the ratio: 100×(total number of reactive groups in said cross-linking agent/total number of disaccharide units in the first hyaluronic acid salt and second hyaluronic acid salt), is theoretically between 0.5 and 70%; and 3) formulating the cross-linked mixture of step 2 ), into a solution buffered to a pH of between 6.5 and 7.5.
2. The hydrogel according to claim 1 , wherein said mixture has an intrinsic viscosity of less than 1900 ml/g.
3. The hydrogel according of claim 1 , wherein said cross-linking agent is selected from bifunctional crosslinking agents and mixtures thereof.
4. The hydrogel according to claim 1 , wherein the degree of cross-linking is theoretically between 4 and 50%.
5. The hydrogel according to claim 1 , wherein said cross-linking agent is selected from epichlorohydrin, divinyl sulfone, 1,4-bis(2,3-epoxypropoxy)butane, 1,2-bis(2,3-epoxypropoxy)ethylene, 1-(2,3-epoxypropyl)-2,3-epoxycyclohexane, aldehydes, and mixtures thereof.
6. The hydrogel according to claim 5 , wherein said aldehydes are selected from formaldehyde, glutaraldehyde, crotonaldehyde, and mixtures thereof.
7. The hydrogel according to claim 1 , wherein said cross-linking agent is 1,4-bis(2,3-epoxypropoxy)butane.
8. The hydrogel according to claim 1 , wherein the pH is between 7 and 7.4.
9. The hydrogel according to claim 1 , wherein the pH is between 7.1 and 7.3.