# US 5,348,939 A · Fibronectin-containing ophthalmic solution, method of preserving an ophthalmic solution, and method of treatment of ophthalmic wounds > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 5,348,939 A - Document ID: US5348939A - Status: Granted - Kind: A - Application number: 08/060,224 - Filed: 1993-05-11 - Granted: 1994-09-20 - Earliest claimed: 1991-11-27 - Assignees: New York Blood Center, Inc.; JCR Pharmaceuticals Co., Ltd.; Santen Pharmaceutical Co., Ltd. - Inventors: Bernard Horowitz; Richard W. Shulman; Adrianne J. Setton; Toyohiko Nishimura; Yoichi Kawashima - Web page: https://patentgrep.com/patent/US5348939A ## CPC - A61K 38/39: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG] - A61K 9/0048: {Eye, e.g. artificial tears} - A61P 27/02: Ophthalmic agents - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract A stable and soluble multi-dose ophthalmic solution is disclosed. The solution contains fibronectin, an amino acid, a sugar, and a lower alkyl p-hydroxybenzoate. A method of treatment of ophthalmic wounds employing the ophthalmic solution, a process for preparing fibronectin for ophthalmic use, a method of lyophilizing an aqueous solution of fibronectin free of albumin, a method for inhibiting bacterial growth in an ophthalmic solution while preserving the cellular adhesion and wound healing activities of fibronectin, and a method of treatment of ophthalmic wounds administering a wound-healing accelerator solution are also disclosed. ## Claims ### Claim 1 A stable and soluble multi-dose ophthalmic solution comprising a therapeutically effective amount Of fibronectin, an amino acid selected from the group consisting of water-soluble hydrophilic amino acids and mixtures thereof, a sugar selected from the group consisting of a monosaccharide, a disaccharide, a trisaccharide, a polysaccharide, derivatives thereof, and mixtures thereof, and a lower alkyl p-hydroxybenzoate preservative, said ophthalmic solution being free of albumin. ### Claim 2 (depends on 1) The ophthalmic solution of claim 1 further comprising a potentiating agent selected from the group consisting of ethylenediaminetetraacetic acid and salts thereof. ### Claim 3 (depends on 1) The ophthalmic solution of claim 1, wherein the concentration of fibronectin is from 0.25 to 10.0 mg/ml. ### Claim 4 (depends on 1) The ophthalmic solution of claim 1, wherein the concentration of the amino acid in the solution ranges from 0.00.5 to 0.5M. ### Claim 5 (depends on 1) The ophthalmic solution of claim 1, wherein the concentration of the sugar in the solution is from 0.005 to 0.5M. ### Claim 6 (depends on 1) The ophthalmic solution of claim 1, wherein the amino acid is glycine and the sugar is sucrose. ### Claim 7 (depends on 6) The ophthalmic solution of claim 6, wherein the concentration of glycine 0.04M and the concentration of sucrose is 0.1M. ### Claim 8 (depends on 1) The ophthalmic solution of claim 1, wherein the lower alkyl p-hydroxybenzoate preservative is from 0.002 to 0.25% (w/v) . ### Claim 9 (depends on 1) The ophthalmic solution of claim 1, wherein the lower alkyl p-hydroxybenzoate preservative comprises methyl p-hydroxybenzoate, ethyl p--hydroxybenzoate, propyl p-hydroxybenzoate, butyl p-hydroxybenzoate, or mixtures thereof. ### Claim 10 (depends on 2) The ophthalmic solution of claim 2, wherein the salts of ethylenediaminetetraacetic acid comprise disodium ethylenediaminetetraacetate and disodium dihydrate ethylenediaminetetraacetate. ### Claim 11 (depends on 10) The ophthalmic solution of claim 10, wherein the preservative comprises a combination of ethyl p-hydroxybenzoate and butyl p-hydroxybenzoate together with the potentiating agent. disodium dihydrate ethylenediaminetetraacetate. ### Claim 12 (depends on 11) The ophthalmic solution of claim 11, wherein the concentration of ethyl p-hydroxybenzoate is from 0.005 to 0.17% the concentration of butyl p-hydroxybenzoate is from 0.002 to 0.02%, and the concentration of disodium dihydrate ethylenediaminetetraacetate is from 0.005 to 0.1%. ### Claim 13 (depends on 1) A method of treatment of an ophthalmic wound comprising administering to the wound a therapeutically effective wound-healing amount of the ophthalmic solution of claim 1. ### Claim 14 (depends on 13) The method of claim 13, wherein the ophthalmic solution further comprises a potentiating agent selected from the group consisting of ethylenediaminetetraacetic acid and salts thereof. ### Claim 15 (depends on 14) The method of claim 14, wherein the preservative comprises a combination of ethyl p-hydroxybenzoate and butyl p-hydroxybenzoate, together with disodium dihydrate ethylenediaminetetraacetate. ### Claim 16 A method for inhibiting bacterial growth in an ophthalmic solution comprising fibronectin, an amino acid selected from the group consisting of water-soluble hydrophilic amino acids and mixtures thereof, and a sugar selected from the group consisting of a monosaccharide, a disaccharide, a trisaccharide, a polysaccharide, derivatives thereof, and mixtures thereof, while preserving the cellular adhesion and wound healing properties of fibronectin, said method comprising adding to said ophthalmic solution a lower alkyl p-hydroxybenzoate preservative in an amount sufficient to inhibit bacterial growth in said ophthalmic solution.