Devices for improved wound management

• US 6,627,215 B1
• Filed: 03/31/1999
• Issued: 09/30/2003
• Est. Priority Date: 12/30/1998
• Status: Expired due to Term

• Current Assignee: Lakewood Amedex Inc.
• Original Assignee: Oligos Etc., Inc.
• Inventors: Arrow, Amy, Gatton, Steven L., Dale, Roderic M. K.
• Primary Examiner(s): Priebe, Scott D.
• Assistant Examiner(s): CHEN, SHIN LIN
• Application Number:
  US09/281,858
• Time in Patent Office: 1,644 Days
• Field of Search: 424/1.29, 424/443, 424/445, 424/447, 424/448, 424/484, 536/23.1, 514/44, 606/228, 602/48
• US Class Current: 424/443
• CPC Class Codes: A01N 57/16 containing heterocyclic radicals
• CPC Class Codes: A61B 17/06166 Sutures suture materials A61L17/00; manufacture of artificial threads D01D; treatment of threads D06M
• CPC Class Codes: A61B 2017/00893 pharmaceutically effective
• CPC Class Codes: A61K 31/70 Carbohydrates; Sugars; Derivatives thereof sorbitol A61K31/047
• CPC Class Codes: A61K 8/606 Nucleosides; Nucleotides; Nucleic acids
• CPC Class Codes: A61L 15/46 Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
• CPC Class Codes: A61L 17/005 containing a biologically active substance, e.g. a medicament or a biocide
• CPC Class Codes: A61L 17/04 Non-resorbable materials
• CPC Class Codes: A61L 17/105 Polyesters not covered by A61L17/12
• CPC Class Codes: A61L 2300/258 Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 24/0015 Medicaments; Biocides
• CPC Class Codes: A61L 24/106 Fibrin; Fibrinogen
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/60 Materials for use in artificial skin
• CPC Class Codes: A61P 31/02 Local antiseptics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin

Abstract

The present invention provides devices and compositions for the management of infection of topical lesions, each of the devices and compositions containing protonated/acidified nucleic acids either on its surface, or integrated into the device. These modified nucleic acids are effective as bactericidal and/or bacteriostatic agents without regard to the class of bacteria, so are especially useful when diagnosis is difficult or when multiple infectious organisms are present. The antibiotic activity of nucleic acids of the invention is not dependent on either the specific sequence of the nucleic acid or the length of the nucleic acid molecule. The nucleic acids used in the invention are protonated/acidified to give a pH when dissolved in water of less than pH 7 to about 1, more preferably less than pH 4.5 to about 1, and even more preferably less than pH 2 to about 1.

Claims

1. A wound dressing comprising:

(a) a solid substrate; and

(b) an antibacterial formulation comprising a protonated/acidified nucleic acid of up to 100 nucleotides, wherein said protonated/acidified nucleic acid comprises a backbone structure modified from that of naturally occurring nucleic acids, and wherein said protonated/acidified nucleic acid has a pH of about 1.0 to about 4.5 when dissolved in water.

3. The wound dressing of claim 1 or 2, wherein the formulation of said protonated/acidified nucleic acid is from about 0.1 to about 5 percent of the dressing dry weight.

4. The wound dressing of claim 1 or 2, wherein the formulation of said protonated/acidified nucleic acid is a coating on said substrate.

5. The wound dressing of claim 4, further comprising a polymeric film bonded to one side of said coated solid substrate.

6. The wound dressing of claim 1 or 2, wherein the formulation of said protonated/acidified nucleic acid is interspersed in the solid substrate.

7. The wound dressing of claim 1 or 2, wherein said polymeric film has a thickness of about 0.001 inch +/−

about 0.0005 inch.

8. The wound dressing of claim 1 or 2, wherein the solid substrate comprises a polyester mesh netting formed of woven multifilament polyester.

2. A wound dressing comprising:

(a) a solid substrate; and

(b) an antibacterial formulation comprising a protonated/acidified nucleic acid monomer, wherein said monomer comprises a blocking chemical modification at the 5′

position of the monomer and a blocking chemical modification at the 3′

position of the monomer, and wherein said protonated/acidified nucleic acid has a pH of about 1.0 to about 4.5 when dissolved in water.

9. A suture comprising:

(a) a pliable solid substrate; and

(b) an antibacterial formulation comprising a protonated/acidified nucleic acid of up to 100 nucleotides, wherein said protonated/acidified nucleic acid comprises a backbone structure modified from that of naturally occurring nucleic acids, and wherein said protonated/acidified nucleic acid has a pH of about 1.0 to about 4.5 when dissolved in water.

10. A suture comprising:

(a) a pliable solid substrate; and

(b) an antibacterial formulation comprising a protonated/acidified nucleic acid monomer, wherein said monomer comprises a blocking chemical modification at the 5′

position of the monomer and a blocking chemical modification at the 3′

position of the monomer, and wherein said protonated/acidified nucleic acid has a pH of about 1.0 to about 4.5 when dissolved in water.

11. The suture of claim 9 or 10, wherein the formulation of nucleic acid is from about 0.1 to about 5 percent of the dry weight of the suture.

12. The suture of claim 9 or 10, wherein the solid substrate is comprised of synthetic materials.

13. The suture of claim 12, wherein the solid substrate is a polyester.

14. The suture of claim 9 or 10, wherein the suture is a nonabsorbable suture.

20. A surgical drape comprising:

(a) a sheet of polymeric substrate; and

(b) a coating of an adhesive composition of claim 10.

21. The surgical drape of claim 20, wherein said substrate comprises a sheet of a polyester.

15. An adhesive composition having antibiotic properties for skin contact applications comprising:

(a) an adhesive polymer; and

(b) an antibacterial formulation dispersed throughout said polymer comprising a protonated/acidified nucleic acid of up to 100 nucleotides, wherein said protonated/acidified nucleic acid comprises a backbone structure modified from that of naturally occurring nucleic acids, and wherein said protonated/acidified nucleic acid has a pH of about 1.0 to about 4.5 when dissolved in water.

17. The adhesive composition of claim 15 or 16, wherein said adhesive polymer comprises a mixture of a low molecular weight solid acrylic polymer and a medium molecular weight solid acrylic polymer.

18. The adhesive composition of claim 15 or 16, further comprising an effective amount of a tackifier.

19. The adhesive composition of claim 15 or 16, wherein the concentration of nucleic acid in said polymer composition is about 0.1% to about 2% by weight.

16. An adhesive composition having antibiotic properties for skin contact applications comprising:

(a) an adhesive polymer; and

(b) an antibacterial formulation comprising a protonated/acidified nucleic acid monomer, wherein said monomer comprises a blocking chemical modification at the 5′

position of the monomer and a blocking chemical modification at the 3′

position of the monomer, and wherein said protonated/acidified nucleic acid has a pH of about 1.0 to about 4.5 when dissolved in water.

22. A wound sealant comprising:

(a) a fibrinogen activator in a concentration sufficient to initiate clot formation; and

(b) an antibacterial formulation comprising a protonated/acidified nucleic acid of up to 100 nucleotides, wherein said protonated/acidified nucleic acid comprises a backbone structure modified from that of naturally occurring nucleic acids, and wherein said protonated/acidified nucleic acid has a pH of about 1.0 to about 4.5 when dissolved in water.

24. The wound sealant of claim 22 or 23, wherein the fibrinogen activator is selected from the group consisting of thrombin and batroxobin.

25. The wound sealant of claim 22 or 23, further comprising fibrinogen.

26. The would sealant of claim 22 or 23, wherein the concentration of nucleic acids in said wound sealant is about 0.5% to about 40% by weight.

23. A wound sealant comprising:

(a) a fibrinogen activator in a concentration sufficient to initiate clot formation; and

(b) an antibacterial formulation comprising a protonated/acidified nucleic acid monomer, wherein said monomer comprises a blocking chemical modification at the 5′

position of the monomer and a blocking chemical modification at the 3′

position of the monomer, and wherein said protonated/acidified nucleic acid has a pH of about 1.0 to about 4.5 when dissolved in water.

27. A skin substitute comprising:

(a) a flexible support surface; and

(b) an antibacterial formulation comprising a protonated/acidified nucleic acid of up to 100 nucleotides, wherein said protonated/acidified nucleic acid comprises a backbone structure modified from that of naturally occurring nucleic acids, and wherein said protonated/acidified nucleic acid has a pH of about 1.0 to about 4.5 when dissolved in water.

29. The skin substitute of claim 27 or 28, wherein the nucleic acid is impregnated into the support surface.

30. The skin substitute of claim 27 or 28, wherein the nucleic acid is coated onto the support surface.

31. The skin substitute of claim 27 or 28, wherein the concentration of nucleic acids in said skin substitute is about 0.1% to about 2% by weight.

28. A skin substitute comprising:

(a) a flexible support surface; and

(b) an antibacterial formulation comprising a protonated/acidified nucleic acid monomer, wherein said monomer comprises a blocking chemical modification at the 5′

position of the monomer and a blocking chemical modification at the 3′

position of the monomer, and wherein said protonated/acidified nucleic acid has a pH of about 1.0 to about 4.5 when dissolved in water.