Method for treating chronic wounds with an extracellular polymeric substance solvating system

• US 8,784,790 B2
• Filed: 06/11/2009
• Issued: 07/22/2014
• Est. Priority Date: 06/12/2008
• Status: Active Grant

• Current Assignee: Medtronic Xomed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Xomed Incorporated (Medtronic Plc)
• Inventors: Myntti, Matthew F., Oliver, Dana A., Hissong, James B., Medina, Jennifer G.
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): EBRAHIM, NABILA G
• Application Number:
  US13/124,380
• Publication Number:
  US 20110245757A1
• Time in Patent Office: 1,867 Days
• Field of Search: None
• US Class Current: 424/78.06
• CPC Class Codes: A61B 17/3203 Fluid jet cutting instruments
• CPC Class Codes: A61B 17/3205 Excision instruments
• CPC Class Codes: A61B 2017/320004 abrasive
• 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 31/09 having two or more such linkages
• CPC Class Codes: A61K 31/19 Carboxylic acids, e.g. valproic acid salicylic acid A61K31/60
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/7036 having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
• CPC Class Codes: A61K 33/22 Boron compounds
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Chronic wounds may be treated by debriding necrotic and other devitalized tissue from the wound, and applying to the wound an extracellular polymeric substance solvating system comprising a metal ion sequestering agent, surfactant and buffering agent. The solvating system disrupts biofilms which may be present in the wound and aids or enables the resumption of normal healing.

Claims

1. A method for treating chronic wounds, which method comprises:

a) debriding at least some necrotic or other devitalized tissue from a chronic skin wound through which subdermal or deeper tissue is exposed, and

b) applying to healthy or healable tissue in the wound an extracellular polymeric substance solvating system comprising an aqueous solution of a metal ion sequestering agent, surfactant and buffering agent wherein the solvating system has an osmolarity greater than 900 milliosmoles of solute per liter.

2. A method according to claim 1 wherein the debriding and applying steps are combined by applying the solvating system at a sufficient flow rate or using sufficient pressure to debride at least some devitalized tissue from the wound.

3. A method according to claim 1 comprising applying the solvating system by spraying, lavage, misting, mopping, wicking or dripping and further comprising removing the solvating system from the wound by flushing, rinsing, draining or absorption.

4. A method according to claim 1 wherein the solvating system has an osmolarity of about 1,000 to about 4,000 milliosmoles of solute per liter.

5. A method according to claim 1 wherein the solvating system has an osmolarity of about 1,500 to about 2,600 milliosmoles of solute per liter.

6. A method according to claim 1 wherein the metal ion sequestering agent comprises a mild acid whose acidity is sufficient to sequester one or more metal ions in a bacterial biofilm but which is not so acidic so as to harm healthy or healable tissue in the wound.

7. A method according to claim 1 wherein the metal ion sequestering agent comprises a sequestering agent for sodium, calcium or iron.

8. A method according to claim 1 wherein the metal ion sequestering agent comprises a carboxylic acid, diacid, triacid or mixture thereof.

9. A method according to claim 8 wherein the metal ion sequestering agent comprises formic acid, acetic acid, chloroacetic acid, dichloroacetic acid, oxalic acid, oxamic acid, glycolic acid, lactic acid, pyruvic acid, aspartic acid, fumaric acid, maleic acid, succinic acid, iminodiacetic acid, glutaric acid, 2-ketoglutaric acid, glutamic acid, adipic acid, glucuronic acid, mucic acid, nitrilotriacetic acid, salicylic acid, ketopimelic acid, benzoic acid, mandelic acid, chloromandelic acid, phenylacetic acid, phthalic acid, boric acid or mixture thereof.

10. A method according to claim 8 wherein the metal ion sequestering agent comprises citric acid.

11. A method according to claim 1 wherein the metal ion sequestering agent is present at a concentration of about 0.01 to about 1.5 M.

12. A method according to claim 1 wherein the surfactant comprises a zwitterionic surfactant.

13. A method according to claim 1 wherein the surfactant is about 0.3% to about 30% of the solvating system.

14. A method according to claim 1 wherein the solvating system comprises sufficient buffering agent so that the solvating system has a pH greater than about 4.

15. A method according to claim 1 wherein the solvating system comprises sufficient buffering agent so that the solvating system has a pH greater than about 5 and less than about 8.5.

16. A method according to claim 1 wherein the solvating system further comprises an antimicrobial agent.

17. A method according to claim 16 wherein the antimicrobial agent comprises a topical antibiotic.

18. A method according to claim 16 wherein the antimicrobial agent comprises a peptide.

19. A method according to claim 16 wherein the antimicrobial agent comprises a bacterially selective peptide.

20. A method according to claim 16 wherein the antimicrobial agent comprises gallium acetoacetonate, gallium bromide, gallium chloride, gallium fluoride, gallium iodide, gallium maltolate, gallium nitrate, gallium nitride, gallium percolate, gallium phosphite, gallium sulfate or mixture thereof.

21. A method according to claim 1 comprising treating a foot or leg wound in a diabetic patient.

22. A method according to claim 1 comprising treating the wound to disrupt a bacterial biofilm and discourage its return.

24. A method according to claim 1 comprising performing debriding step a) using an extracellular polymeric substance solvating system of step b).

25. A method according to claim 1 wherein the solvating system has an osmolarity greater than 900 milliosmoles of solute per liter.

26. A method according to claim 1 wherein the solvating system has an osmolarity of at least 1,000 milliosmoles of solute per liter.

23. A method for treating a chronic wound, which method comprises applying to healthy or healable tissue in a chronic skin wound through which subdermal or deeper tissue is exposed an extracellular polymeric substance solvating system comprising an aqueous solution of a metal ion sequestering agent, surfactant and buffering agent and having an osmolarity of about 1,000 to about 4,000 milliosmoles of solute per liter.