Wound Dressings For The Controlled Release Of Therapeutic Agents

Patent metadata

Field	Value
Publication number	US-2017333592-A1
Application number	US-201715612831-A
Country	US
Kind code	A1
Filing date	Jun 2, 2017
Priority date	Nov 24, 2003
Publication date	Nov 23, 2017
Grant date	—

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).

First claim

1 . A wound dressing material for controlled activation of a wound healing therapeutic compound in the presence of an enzyme in a wound fluid, the material comprising:
a medically acceptable polymer; a therapeutic agent; an inhibitor of the enzyme; and a linker group which is cleavable by the enzyme; wherein the activities of both the therapeutic agent and the inhibitor are increased by contacting the wound dressing material with a wound fluid containing the enzyme.

2 . A wound dressing material according to claim 1 , wherein the therapeutic agent and the inhibitor are dispersed in a matrix of the medically acceptable polymer, and the polymer comprises the linker group.

3 . A wound dressing material according to claim 2 , wherein the polymer is cross-linked by the linker group.

4 . A wound dressing material according to claim 1 , wherein the therapeutic agent and the inhibitor are conjugated to the medically acceptable polymer by the linker group.

5 . A wound dressing material according to claim 1 , wherein the therapeutic agent is conjugated to the inhibitor by the linker group.

6 . A wound dressing material according to claim 1 wherein elevated levels of the enzyme are associated with pain, wound infection or wound chronicity.

7 . A wound dressing material according to claim 1 , wherein the enzyme is a protease, and the linker group comprises an oligopeptidic sequence which is a substrate for the protease.

8 . A wound dressing material according to claim 7 , wherein the protease is elastase and wherein the oligopeptidic sequence comprises or consists of 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.

9 . A wound dressing material according to claim 7 , wherein the protease is a matrix metalloproteinase and wherein the oligopeptidic sequence comprises or consists of -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.

10 . A wound dressing material according to claim 7 , wherein the protease is a collagenase and wherein the oligopeptidic sequence comprises or consists of -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.

11 . A wound dressing material according to claim 7 , wherein the protease is a gelatinase and wherein the oligopeptidic sequence comprises or consists of -Pro-Leu-Gly-Met-Trp-Ser-Arg-.

12 . A wound dressing material according to claim 7 , wherein the protease is thrombin and wherein the oligopeptidic sequence comprises or consists of -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-.

13 . A wound dressing material according to claim 7 , wherein the protease is stromelysin and wherein the oligopeptidic sequence comprises or consists of -Pro-Tyr-Ala-Tyr-Trp-Met-Arg-.

14 . A wound dressing material according to claim 1 wherein the therapeutic agent is a reactive oxygen scavenger, an antimicrobial agent, a pain relieving agent, an antiseptic, an analgesic, or a local anaesthetic.

15 . A wound dressing material according to claim 14 , wherein the therapeutic agent comprises 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 mixtures thereof.

16 . 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.

17 . A wound dressing comprising a wound dressing material according to claim 1 .

18 . (canceled)

Assignees

• Kci Usa Inc

Inventors

• Cullen Breda Mary
• Gregory Sara Jayne

Classifications

• A61L2300/45

  Mixtures of two or more drugs, e.g. synergistic mixtures · CPC title

• A61L2300/604

  Biodegradation · CPC title

• A61L2300/434

  of enzymes · CPC title

• A61L15/44

  Medicaments · CPC title

• A61L2300/412

  Tissue-regenerating or healing or proliferative agents · CPC title