Wound healing compositions
Provided herein are biologically active solution compositions comprising one or more sacrificial proteolytic enzyme substrates, one or more preservatives, and one or more antimicrobial agents and methods of using the solution compositions to treat tissue sites, in particular chronic wounds. The compositions may be used in conjunction with negative pressure wound therapy to treat tissue sites.
1. A method of treating a tissue site, comprising:
delivering via instillation a composition in a dispensable liquid form to the tissue site, wherein the composition comprises:
one or more matrix metalloprotease (MMP) substrates, wherein the MMP substrates comprise gelatin or a hydrolysate thereof,
one or more preservatives comprising a chelating agent, wherein the chelating agent is ethylenediaminetetraacetic acid (EDTA), and
a pharmaceutically-acceptable carrier; and
applying negative pressure to the tissue site to remove at least a portion of the composition delivered to the tissue site.
2. The method of claim 1 , wherein the tissue site is treated with the composition prior to applying negative pressure.
3. The method of claim 1 , wherein the tissue site is treated with the composition after applying negative pressure.
4. The method of claim 1 , wherein the tissue site is treated with the composition while applying negative pressure.
5. The method of claim 1 , wherein the method further comprises applying a dressing to the tissue site, wherein the dressing is connected to a pressure source for applying negative pressure to the tissue site, and wherein the composition flows through the dressing to the tissue site.
6. The method of claim 5 , wherein the dressing comprises an open-cell reticulated polyurethane foam pad.
7. The method of claim 6 , wherein the method further comprises treating the foam pad with the composition prior to use.
8. The method of claim 7 , wherein the foam pad is infused and coated on the surface with the composition.
9. The method of claim 6 , wherein the method comprises continuous instillation of the composition to the tissue site.
10. The method of claim 6 , wherein the method comprises periodic instillation of the composition to the tissue site.
11. The method of claim 1 , wherein the method of treating the tissue site comprises continuous instillation of the tissue site with the composition.
12. The method of claim 1 , wherein the method of treating the tissue site comprises periodic instillation of the tissue site with the composition.
13. The method of claim 1 , wherein the composition further comprises one or more antimicrobial agents.
14. The method of claim 1 , wherein the composition further comprises one or more growth factors.
15. The method of claim 1 , wherein the composition further comprises one or more proteinase inhibitors.
16. The method of claim 1 , wherein the gelatin comprises a molecular weight of between 2000 Da to 20,000 Da.
17. The method of claim 1 , wherein the gelatin has a bloom value of less than 150.
18. The method of claim 1 , wherein the one or more preservatives further comprises sodium benzoate.
19. A system for treating a tissue site, the system comprising:
a negative-pressure source;
a container adapted to contain a composition, wherein the composition comprises:
one or more matrix metalloprotease (MMP) substrates, wherein the MMP substrates comprise gelatin or a hydrolysate thereof,
one or more preservatives comprising a chelating agent, wherein the chelating agent is ethylenediaminetetraacetic acid (EDTA), and
a pharmaceutically-acceptable carrier;
a dressing in fluid communication with the negative-pressure source and adapted to distribute negative pressure to the tissue site, wherein the dressing has a first portion adapted for contact with the tissue site, and a second portion in fluid communication with the container;
a pump adapted to deliver the composition to the dressing; and
a drape adapted to cover the dressing.
20. The system of claim 19 , wherein the dressing is infused and coated with the composition.
21. The system of claim 19 , wherein the composition further comprises one or more antimicrobial agents, one or more growth factors, and one or more proteinase inhibitors that are proteinase inhibitors of MMPs.
22. The system of claim 21 , wherein the composition is a solution.
23. The system of claim 22 , wherein the one or more preservatives comprises sodium benzoate, potassium sorbate, or sodium nitrate.
24. The system of claim 19 , wherein the dressing comprises an open-cell reticulated polyurethane foam pad.
25. The system of claim 24 , wherein the foam pad is treated with the composition prior to use.
26. The system of claim 25 , wherein the foam pad is infused and coated on the surface with the composition.
27. The system of claim 19 , wherein the gelatin comprises a molecular weight of between 2000 Da to 20,000 Da.
28. The system of claim 19 , wherein the gelatin has a bloom value of less than 150.
29. The system of claim 19 , wherein the one or more preservatives further comprises sodium benzoate.
30. The system of claim 19 , wherein the composition is provided in a dispensable liquid form for instillation to the tissue site.
31. A method of delivering a composition consisting essentially of one or more matrix metalloprotease (MMP) substrates comprising gelatin or a hydrolysate thereof, one or more preservatives comprising a chelating agent comprising ethylenediaminetetraacetic acid (EDTA), and a pharmaceutically acceptable carrier, and optionally further comprising a component selected from the group consisting of a proteinase inhibitor, an antimicrobial agent, a growth factor, and combinations thereof; wherein the composition is provided in a dispensable liquid form for instillation to a tissue site.
32. The method of claim 31 , wherein the antimicrobial agent comprises polyhexanide biguanide (PHMB).
33. The method of claim 31 , wherein the gelatin comprises a molecular weight of between 2000 Da to 20,000 Da.
34. The method of claim 31 , wherein the gelatin has a bloom value of less than 150.
35. The method of claim 31 , wherein the one or more preservatives further comprises sodium benzoate.