Wound dressings, methods of using the same and methods of forming the same
View Patent ↗Provided according to some embodiments of the invention are wound dressings that include a polymer matrix and nitric oxide-releasing polysiloxane macromolecules within and/or on the polymer matrix. Also provided are wound dressing kits and methods of using and forming such wound dressings.
1. A wound dressing comprising a polymer matrix, and
nitric oxide (NO)-releasing polysiloxane macromolecules within the polymer matrix,
wherein the NO-releasing polysiloxane macromolecules are NO-releasing particles that have a molar mass of at least 500 Da and a diameter in a range of 0.1 nm to 100 μm, and the polymer matrix comprises a polyurethane foam, and
wherein the wound dressing is non-toxic and stably stores NO.
2. The wound dressing of claim 1 , wherein the NO-releasing polysiloxane macromolecules comprise N-diazeniumdiolate functional groups.
3. The wound dressing of claim 1 , wherein the NO-releasing polysiloxane macromolecules comprise S-nitrosothiol functional groups.
4. The wound dressing of claim 1 , wherein the NO-releasing polysiloxane macromolecules are present at a concentration in a range of about 0.1 to about 20 weight percent of the polymer matrix.
5. The wound dressing of claim 1 , further comprising a water-soluble porogen selected from the group consisting of sodium chloride, sucrose, glucose, lactose, sorbitol, xylitol, polyethylene glycol, polyvinylpyrrollidone, polyvinyl alcohol and mixtures thereof.
6. The wound dressing of claim 1 , further comprising at least one therapeutic agent selected from the group consisting of antimicrobial compounds, anti-inflammatory agents, pain-relievers, immunosuppressants, vasodilators, wound healing agents, anti-biofilm agents and mixtures thereof.
7. The wound dressing of claim 1 , wherein the polyurethane foam comprises at least one polyisocyanate segment and at least one polyol segment.
8. The wound dressing of claim 7 , wherein the at least one polyisocyanate segment is formed from a polyisocyanate selected from the group consisting of tolylene diisocyanate, methylphenylene diisocyanate, modified diisocyanates, and mixtures thereof.
9. The wound dressing of claim 7 , wherein the at least one polyol segment is formed from at least one diol having from 2 to 18 carbon atoms.
10. The wound dressing of claim 9 , wherein the at least one diol having from 2 to 18 carbon atoms is selected from the group consisting of 2-ethanediol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,5-pentanediol, 1,10-decanediol, 2-methyl-1,3-propanediol, 2-methyl-2-butyl-1,3-propanediol, 2,2-dimethyl-1,3-propanediol, 2,2-dimethyl-1,4-butanediol, 2-ethyl-2-butyl-1,3-propanediol, neopentyl glycol hydroxypivalate, diethylene glycol, triethylene glycol and mixtures thereof.
11. The wound dressing of claim 1 , wherein the wound dressing is a single layer with a thickness ranging from 10 to 5000 microns.
12. The wound dressing of claim 1 , wherein the wound dressing is substantially transparent.
13. The wound dressing of claim 1 , wherein nitric oxide is released from the hydrated dressing surface at a flux in a range of 0.1 pmol NO cm −2 to 100 pmol NO cm −2 .
14. The wound dressing of claim 1 , wherein nitric oxide is stored in the dressing in an amount in a range of 100 pmol NO cm −2 to 1000 pmol NO cm −2 .
15. The wound dressing of claim 1 , wherein nitric oxide is stored in the dressing in an amount in a range of 1 nmol NO cm −2 to 10 μmol NO cm −2 .
16. A method for treating a wound comprising applying a wound dressing of claim 1 to a wound.
17. The method of claim 16 , further comprising debriding the wound prior to applying the wound dressing.
18. The method of claim 16 , further comprising performing negative pressure wound therapy to the wound prior to, concurrently with or after applying the wound dressing.
19. The method of claim 18 , whereby the negative pressure wound therapy device and the wound dressing of claim 1 is configured as one device.
20. The method of claim 16 , further comprising treating the wound with an anti-biofilm agent prior to or in combination with the application of the wound dressing.
21. The wound dressing of claim 1 , wherein the wound dressing comprises
a first layer that, when applied to a wound bed, contacts the wound bed and is non-interactive with the wound bed, and
a second layer on the first layer.
22. The wound dressing of claim 21 , wherein the first layer is substantially free of NO-releasing macromolecules and comprises at least one therapeutic agent, and wherein the second layer comprises the polymer matrix having NO-releasing polysiloxane macromolecules therein.
23. The wound dressing of claim 1 , wherein at least 95% of the NO is retained in the wound dressing after one week at 25° C.
24. The wound dressing of claim 1 , wherein greater than 98% of the NO-releasing polysiloxane macromolecules are retained in the wound dressing after incubation of the wound dressing in phosphate buffered saline at pH 7.4 for 48 hours at 37° C.
25. A method of forming a wound dressing, comprising:
combining NO-releasing polysiloxane macromolecules and at least one monomer, wherein the NO-releasing polysiloxane macromolecules are NO-releasing particles that have a molar mass of at least 500 Da and a diameter in a range of 0.1 nm to 100 μm; and
polymerizing the at least one monomer to form a polymer matrix comprising the NO-releasing polysiloxane macromolecules, wherein the polymer matrix comprises a polyurethane foam.
26. The method of claim 25 , wherein the monomer is polymerized by photocuring.
27. The method of claim 25 , wherein the polymerization occurs by a method comprising depositing liquid monomer, NO-releasing polysiloxane macromolecules and an initiator; and polymerizing the liquid monomer.
28. The method of claim 25 , wherein combining NO-releasing polysiloxane macromolecules and at least one monomer comprises dispersing the NO-releasing macromolecules in a mixture of foam forming monomers;
wherein polymerizing the at least one monomer to form a polymer matrix comprises polymerizing the foam forming monomers to form a polymer, and foaming the polymer to form the polymer matrix.
29. The method of claim 28 , wherein the polymer foam is formed by the use of a blowing agent selected from at least one of the group consisting of carbon dioxide, hydrohalo-olefins and alkanes.
30. The method of claim 29 , wherein the blowing agent includes carbon dioxide generated from carbamates that are formed from alkanolamines selected from at least one of the group consisting of 2-(2-aminoethylamino)ethanol, (3-[(2-aminoethyl)amino)]propanol), (2-[(3-aminopropyl)amino]ethanol), (1-[(2-aminoethypamino]-2-propanol, (2-[(3-aminopropyl)methylamino]ethanol, 1-[(2-amino-1-methylethyl)amino]-2-propanol, 2-[((2-amino-2-methylpropyl)amino]-2-methyl-1-propanol, 2-[(4-amino-3-methylbutypamino]-2-methyl-1-propanol, 17-amino-3,6,9,12,15-pentaazaheptadecan-1-ol and 3,7,12,16-tetraazaoctadecane-1,18-diol.
31. The method of claim 25 , wherein combining NO-releasing polysiloxane macromolecules and at least one monomer comprises reacting functional groups on the NO-releasing macromolecules with at least one foam forming monomer;
wherein polymerizing the at least one monomer to form a polymer matrix comprises polymerizing the foam forming monomers to form a polymer, and foaming the polymer to form the polymer matrix.
32. A wound dressing kit, comprising one or more of
a first wound dressing that releases low concentrations of nitric oxide over 0 to 7 days in the range of 0.5 pmol NO cm −2 s −1 to 20 pmol NO cm −2 s −1 upon initial application to the patient;
a second wound dressing that releases intermediate concentrations of nitric oxide over 0 to 7 days in the range of 20 pmol NO cm −2 s −1 to 1000 pmol NO cm −2 s −1 upon initial application to the patient; and
a third wound dressing that releases high levels of nitric oxide for 0 to 48 hours in the range of 1 nmol NO cm −2 s −1 to 1 μmol NO cm −2 s −1 upon initial application to the patient,
wherein each of the wound dressings comprises a polymer matrix and NO-releasing polysiloxane macromolecules within the polymer matrix, wherein the NO-releasing polysiloxane macromolecules are NO-releasing particles that have a molar mass of at least 500 Da and a diameter in a range of 0.1 nm to 100 μm and the polymer matrix comprises a polyurethane foam, and wherein each wound dressing is non-toxic and can stably store nitric oxide.
33. The wound dressing kit of claim 32 , wherein the second wound dressing further includes an anti-inflammatory agent.
34. The wound dressing kit of claim 32 , wherein the third wound dressing further includes an anti-microbial agent.