# US 10,307,505 B2 · Wound dressings for the controlled release of therapeutic agents > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,307,505 B2 - Document ID: US10307505B2 - Status: Granted - Kind: B2 - Application number: 15/612,831 - Filed: 2017-06-02 - Published: 2017-11-23 - Granted: 2019-06-04 - Earliest claimed: 2003-11-24 - Assignees: KCI USA, Inc. - Applicants: Kci USA, Inc. - Inventors: Breda Mary Cullen; Sara Jayne Gregory - Web page: https://patentgrep.com/patent/US10307505B2 ## CPC - A61L 15/32: Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin {(A61L15/225 takes precedence)} - A61L 15/18: containing inorganic materials - A61L 15/44: Medicaments - A61L 2300/412: Tissue-regenerating or healing or proliferative agents - A61L 2300/434: of enzymes - A61L 2300/45: Mixtures of two or more drugs, e.g. synergistic mixtures - A61L 2300/604: Biodegradation - A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K) ## Abstract A wound dressing material for controlled activation of a wound healing therapeutic compound in the presence of a protease enzyme in a wound fluid, the material comprising: a medically acceptable polymer; a wound healing therapeutic agent; an inhibitor of the protease enzyme; and a linker group which is cleavable by the protease enzyme wherein the activities of both the wound healing therapeutic agent and the inhibitor increased by contacting the wound dressing material with a would fluid containing the protease enzyme. For example, the enzyme may be a matrix metalloproteinase, the therapeutic agent may be a reactive oxygen scavenger, and the inhibitor may be a tissue inhibitor of metalloproteinase (TIMP). ## Claims ### Claim 1 A wound dressing material for controlled activation of a wound healing therapeutic compound in the presence of a protease in a wound fluid, the material comprising: a medically acceptable polymer cross-linked by an oligopeptidic sequence; a therapeutic agent comprising a reactive oxygen scavenger selected from the group consisting of antioxidant phenol derivatives, vitamin E, methyl peroxide antioxidants, stilbenes, gallocatechins, ubiquinol, retinoids, vitamin A, vitamin C, N-acetyl cysteine, selenium and its compounds, zinc and its compounds, glutathione, carotenoids, papai, thioproline, albumin, chlorophyllin, antioxidant dyestuffs, and mixture or any two or more thereof; and an inhibitor of the protease; wherein the oligopeptidic sequence is cleavable by the protease and is a substrate for the protease; the therapeutic agent and the inhibitor are dispersed in a matrix of the medically acceptable polymer; and the activities of both the therapeutic agent and the inhibitor are increased by contacting the wound dressing material with a wound fluid containing the protease. ### Claim 2 (depends on 1) A wound dressing material according to claim 1 wherein elevated levels of the protease are associated with pain, wound infection or wound chronicity. ### Claim 3 (depends on 1) A wound dressing material according to claim 1, wherein the protease is elastase and wherein the oligopeptidic sequence comprises lys-gly-ala-ala-ala-lys-Ala-Ala-Ala-, Ala-Ala-Pro-Val, Ala-Ala-Pro-Leu, Ala-Ala-Pro-Phe, Ala-Ala-Pro-Ala or Ala-Tyr-Leu-Val. ### Claim 4 (depends on 1) A wound dressing material according to claim 1, wherein the protease is a matrix metalloproteinase and wherein the oligopeptidic sequence comprises -Gly-Pro-Y- Gly-Pro-Z-, -Gly-Pro-Leu-Gly-Pro-Z-, -Gly-Pro-Ile-Gly-Pro-Z-, or-Ala-Pro-Gly-Leu-Z-, where Y and Z are amino acids. ### Claim 5 (depends on 1) A wound dressing material according to claim 1, wherein the protease is a collagenase and wherein the oligopeptidic sequence comprises -Pro-Leu-Gly-Pro-D-Arg- Z-, -Pro-Leu-Gly-Leu-Leu-Gly-Z-, -Pro-Gln-Gly-Ile-Ala-Gly-Trp-, -Pro-Leu-Gly-Cys (Me)- His-,-Pro-Leu-Gly-Leu-Trp-Ala-, -Pro-Leu-Ala-Leu-Trp-Ala-Arg-, or -Pro-Leu-Ala-Tyr-Trp-Ala-Arg-, where Z is an amino acid. ### Claim 6 (depends on 1) A wound dressing material according to claim 1, wherein the protease is a gelatinase and wherein the oligopeptidic sequence comprises -Pro-Leu-Gly-Met-Trp-Ser-Arg-. ### Claim 7 (depends on 1) A wound dressing material according to claim 1, wherein the protease is thrombin and wherein the oligopeptidic sequence comprises -Gly-Arg-Gly-Asp-, -Gly-Gly-Arg-, -Gly-Arg-Gly-Asp-Asn-Pro-, -Gly-Arg-Gly-Asp-Ser-, -Gly-Arg-Gly-Asp-Ser-Pro-Lys-, -Gly-Pro-Arg-, -Val-Pro-Arg-, or -Phe-Val-Arg-. ### Claim 8 (depends on 1) A wound dressing material according to claim 1, wherein the protease is stromelysin and wherein the oligopeptidic sequence comprises -Pro-Tyr-Ala-Tyr-Trp-Met-Arg-. ### Claim 9 (depends on 1) A wound dressing material according to claim 1 wherein the therapeutic agent further comprises an antimicrobial agent, a pain relieving agent, an antiseptic, an analgesic, or a local anaesthetic. ### Claim 10 (depends on 1) A wound dressing material according to claim 1, wherein the inhibitor is selected from the group consisting of Tissue Inhibitor of Metalloproteinase (TIMP), 4-(2-aminoethyl) benzenesulfonyl fluoride AEBSF, antithrombin, (p-Amidinophenyl) methanesulfonyl fluoride APMSF, Aprotinin, diisopropylfluorophosphate DFP, phenyl methyl sulfonyl fluoride PMSF, Antipain, Chymostatin, Leupeptin, Tosyl-lysine chloromethylketone TLCK, Tosyl-phenyl chloromethylketone TPCK, L-trans-epoxysuccinylleucylamido (4-guanidino) butane E-64, Amastatin, Bestatin, Diprotin, Ethylenediamine tetra-acetic acid (EDTA), pepstatin and mixtures thereof. ### Claim 11 (depends on 1) A wound dressing comprising a wound dressing material according to claim 1. ### Claim 12 (depends on 1) A wound dressing material according to claim 1, wherein the medically acceptable polymer comprises an elastin. ### Claim 13 (depends on 1) A wound dressing material according to claim 1, wherein the medically acceptable polymer comprises N-(2-hydroxypropyl)methacrylamide cross-linked with the linker group. ### Claim 14 (depends on 1) A wound dressing material according to claim 1, wherein the medically acceptable polymer comprises chitosan.