Claims for Patent: 10,307,505

Summary for Patent: 10,307,505

Title:	Wound dressings for the controlled release of therapeutic agents
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).
Inventor(s):	Cullen; Breda Mary (Skipton, GB), Gregory; Sara Jayne (West Yorkshire, GB)
Assignee:	KCI USA, INC. (San Antonio, TX)
Application Number:	15/612,831
Patent Claims:	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. 2. A wound dressing material according to claim 1 wherein elevated levels of the protease are associated with pain, wound infection or wound chronicity. 3. 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. 4. 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. 5. 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. 6. 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-. 7. 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-. 8. 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-. 9. 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. 10. 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. 11. A wound dressing comprising a wound dressing material according to claim 1. 12. A wound dressing material according to claim 1, wherein the medically acceptable polymer comprises an elastin. 13. A wound dressing material according to claim 1, wherein the medically acceptable polymer comprises N-(2-hydroxypropyl)methacrylamide cross-linked with the linker group. 14. A wound dressing material according to claim 1, wherein the medically acceptable polymer comprises chitosan.

Details for Patent 10,307,505

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bayer Healthcare Pharmaceuticals Inc.	TRASYLOL	aprotinin	Injection	020304	12/29/1993		2023-11-24
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2023-11-24