ANTIMICROBIAL SILICONE-BASED WOUND DRESSINGS

• US 20110313048A1
• Filed: 06/17/2011
• Published: 12/22/2011
• Est. Priority Date: 06/17/2010
• Status: Active Grant

• Current Assignee: Covalon Technologies Incorporated
• Original Assignee: Covalon Technologies Incorporated
• Inventors: Yang, Liu, DiTizio, Valerio
• Granted Patent: US 10,500,173 B2
• Time in Patent Office: Days
• US Class Current: 514/636
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 33/38 Silver; Compounds thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 15/46 Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
• CPC Class Codes: A61L 15/60 Liquid-swellable gel-forming materials, e.g. super-absorbents
• CPC Class Codes: A61L 2/232 layered or coated
• CPC Class Codes: A61L 2300/104 Silver, e.g. silver sulfadiazine
• CPC Class Codes: A61L 2300/206 Biguanides, e.g. chlorohexidine
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/442 Colorants, dyes
• CPC Class Codes: A61L 26/0066 Medicaments; Biocides
• CPC Class Codes: A61L 26/008 Hydrogels or hydrocolloids
• CPC Class Codes: A61P 31/02 Local antiseptics
• CPC Class Codes: C08L 83/04 Polysiloxanes

Abstract

Antimicrobial silicone-based dressings, such as wound dressings, are disclosed. An example dressing comprises a transparent and self-adhesive gel sheet cured from a liquid containing silicone, the sheet having dispersed therein (i) particulates of a chlorhexidine compound that is not soluble in the liquid; and (ii) at least one other antimicrobial. Methods of making the silicone-based dressings and methods of use are also disclosed.

Claims

1. A method for making a dressing, comprising:

(a) mixing together a liquid containing silicone, a chlorhexidine compound that is not soluble in said liquid and at least one other antimicrobial to form a mixture; and

(b) molding and curing said mixture to form a transparent and self-adhesive gel sheet.

2. The method of claim 1, wherein prior to said mixing, said chlorhexidine compound is blended with said at least one other antimicrobial.

3. The method of claim 1, wherein said curing is conducted in the presence of a catalyst.

4. The method of claim 3, wherein said catalyst is platinum.

5. The method of claim 1, wherein said mixing further comprising adding one or both of chlorhexidine digluconate solution and a photo-stabilized silver agent.

6. The method of claim 5, wherein said chlorhexidine digluconate is provided as a 20% solution.

7. A dressing comprising:

a transparent and self-adhesive gel sheet cured from a liquid containing silicone, the sheet having dispersed therein (i) particulates of a chlorhexidine compound that is not soluble in said liquid; and

(ii) at least one other antimicrobial.

8. The dressing of claim 7, wherein said chlorhexidine compound is chlorhexidine, chlorhexidine dihydrochloride, chlorhexidine diacetate, or any combination thereof.

9. The dressing of claim 8, wherein said chlorhexidine compound is chlorhexidine diacetate.

10. The dressing of claim 7, wherein said at least one other antimicrobial is one or both of chlorhexidine digluconate and a photo-stabilized silver agent.

11. The dressing of claim 10, wherein said at least one other antimicrobial is chlorhexidine digluconate.

12. The dressing of claim 10, wherein said at least one other antimicrobial is said photo-stabilized silver agent.

13. The dressing of claim 10, wherein said photo-stabilized silver agent is silver nitrate, silver acetate or silver lactate, or any combination thereof.

14. The dressing of claim 10, wherein said photo-stabilized silver agent is photo-stabilized with (i) a compound containing a basic nitrogen atom to complex with silver and (ii) a dye.

15. The dressing of claim 14, wherein said compound containing a basic nitrogen atom is one or more of ammonia, tris(hydroxymethyl)aminomethane, D,L-pyroglutamic acid, polyethyleneimine, and an amino acid.

16. The dressing of claim 15, wherein said amino acid is alanine, arginine, asparagine, cysteine, glutamine, glutamate, glycine, histidine, isoleucine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine or valine, or any combination thereof.

17. The dressing of claim 15, wherein said compound containing a basic nitrogen atom is D,L-pyroglutamic acid.

18. The dressing of claim 17, wherein said dye is Brilliant Green, Malachite Green, Methylene Blue, Ethyl Violet, Crystal Violet, Victoria Blue R, Victoria Blue B or Victoria Pure Blue BO, or any combination thereof.

19. The dressing of claim 18, wherein said dye is Brilliant Green.

20. The dressing of claim 7, wherein said dressing comprises chlorhexidine diacetate and chlorhexidine digluconate.

21. The dressing of claim 7, wherein said dressing comprises chlorhexidine diacetate, chlorhexidine digluconate and a photo-stabilized silver agent.

22. The wound dressing of claim 7, wherein said dressing comprises chlorhexidine diacetate and a photo-stabilized silver agent.

23. The dressing of claim 7, wherein a total amount of chlorhexidine is present in an amount of up to 5% by weight of said dressing.

24. The dressing of claim 23, wherein said total amount is about 2% to 5% by weight of said dressing.

25. The dressing of claim 7, wherein said dressing is provided as an I.V. dressing, a wound dressing, a wound barrier, a strip, a first aid bandage or a surgical drape.

26. The dressing of claim 7, wherein said dressing has a thickness of up to about 5mm.

27. A method for preventing infection of a wound or incision site, said method comprising applying the dressing of claim 7 to said wound or incision site.

28. The method of claim 27, wherein said preventing comprises reducing bacterial contamination of the wound or incision site.

29. The method of claim 27, wherein said dressing releases said chlorhexidine compound and said at least one antimicrobial for at least up to 7 days.

30. A method for treating a wound or incision site, the method comprising applying the dressing of claim 7 to said wound or incision site.

31. The method of claim 30, wherein the dressing is applied to said wound or incision site as an I.V. dressing, a wound dressing, a wound barrier, a strip, a first aid bandage or a surgical drape.

32. A method for quantifying chlorhexidine incorporated in a silicone gel sheet, said method comprising:

breaking down a matrix of said silicone gel sheet;

extracting said chlorhexidine with a solvent with a high dielectric constant or with a base saturated alcohol; and

quantifying said chlorhexidine against a chlorhexidine standard.

33. The method of claim 32, wherein said breaking down comprises:

soaking and stirring said silicone gel sheet in an organic solvent with a low dielectric constant, wherein said organic solvent is added to said silicone gel sheet at a ratio of 800-150;

1 (vol;

wt) or 125-100;

1 (vol;

wt).

34. The method of claim 33, wherein said organic solvent with a low dielectric constant is dichloromethane, chloroform, cyclopentane, tetrahydrofuran, hexane, cyclohexane, xylene or heptane, or any combination thereof.

35. The method of claim 32, wherein said solvent with a high dielectric constant is ethanol, methanol or isopropyl alcohol, or any combination thereof.

36. A method for quantifying silver incorporated in a silicone gel sheet, said method comprising:

breaking down a matrix of said silicone gel sheet;

extracting said silver with an aqueous ammonium hydroxide solution; and

quantifying said silver against a silver standard.

37. The method of claim 36, wherein said breaking down comprises

soaking and stirring said silicone gel sheet in an organic solvent with a low dielectric constant followed by stirring in a base saturated alcohol, wherein said organic solvent is added to said silicone gel sheet at a ratio of 100-20:

1 (vol;

wt) or 80-60;

1 (vol;

wt).

38. The method of claim 36, wherein said organic solvent with a low dielectric constant is dichloromethane, chloroform, cyclopentane, tetrahydrofuran, hexane, cyclohexane, xylene or heptane, or any combination thereof.