Wound dressings, methods of using the same and methods of forming the same

Patent metadata

Field	Value
Publication number	US-11583608-B2
Application number	US-201815887649-A
Country	US
Kind code	B2
Filing date	Feb 2, 2018
Priority date	Aug 21, 2009
Publication date	Feb 21, 2023
Grant date	Feb 21, 2023

Abstract

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.

First claim

We claim:

1. A wound dressing comprising:
a polymer matrix comprising a foam, 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,
wherein the polymer matrix comprises a polymer selected from the group consisting of acrylate polymers, acrylic acid polymers, copolymers thereof and blends thereof, 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 , wherein the polymer matrix comprises at least one selected from the group consisting of: hydrophilic polyacrylates, co-polymers of carboxymethylcellulose and acrylic acid, poly(acrylic acid), poly(acrylic acid) derivatives, acrylic acid copolymers, methacrylic acid, methacrylic acid derivatives, and methacrylic acid copolymers.

6. 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.

7. 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.

8. The wound dressing of claim 1 , wherein the wound dressing is a single layer with a thickness ranging from 10 to 5000 microns.

9. The wound dressing of claim 1 , wherein the wound dressing is substantially transparent.

10. The wound dressing of claim 1 , wherein nitric oxide is released from a surface of the wound dressing at a flux in a range of 0.1 pmol NO cm −2 to 100 pmol NO cm −2 .

11. The wound dressing of claim 1 , wherein nitric oxide is stored in the wound dressing in an amount in a range of 100 pmol NO cm −2 to 1000 pmol NO cm −2 .

12. The wound dressing of claim 1 , wherein nitric oxide is stored in the wound dressing in an amount in a range of 1 nmol NO cm 2 to 10 μmol NO cm −2 .

13. 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.

14. The wound dressing of claim 13 , wherein the first layer comprises at least one therapeutic agent and is devoid of NO-releasing macromolecules, and wherein the second layer comprises the polymer matrix having the NO-releasing polysiloxane macromolecules therein.

15. 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.

16. 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.

17. A method for treating a wound comprising applying a wound dressing of claim 1 to a wound.

18. The method of claim 17 , further comprising debriding the wound prior to applying the wound dressing.

19. The method of claim 17 , further comprising performing negative pressure wound therapy to the wound prior to, concurrently with or after applying the wound dressing.

20. The method of claim 19 , whereby a negative pressure wound therapy device and the wound dressing are configured as one device.

21. The method of claim 17 , further comprising treating the wound with an anti-biofilm agent prior to or in combination with the application of the wound dressing.

22. A method of forming a wound dressing, comprising:
combining NO-releasing polysiloxane macromolecules and at least one monomer; and
polymerizing the at least one monomer to form a polymer matrix comprising the NO-releasing polysiloxane macromolecules, 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, wherein the polymer matrix comprises a foam, and wherein the polymer matrix comprises a polymer selected from the group consisting of acrylate polymers, acrylic acid polymers, copolymers thereof and blends thereof.

23. The method of claim 22 , wherein the monomer is polymerized by photocuring.

24. The method of claim 22 , wherein the polymerizing the at least one monomer occurs by a method comprising depositing a liquid monomer, the NO-releasing polysiloxane macromolecules and an initiator; and polymerizing the liquid monomer.

25. The method of claim 22 , wherein combining the NO-releasing polysiloxane macromolecules and the 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.

26. The method of claim 22 , wherein combining the NO-releasing polysiloxane macromolecules and the 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.

27. The method of claim 22 , wherein the 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.

28. The method of claim 27 , wherein the blowing agent comprises 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-aminoethyl)amino]-2-propanol, (2-[(3-aminopropyl)methylaminol]ethanol, 1-[(2-amino-1-methylethyl)amino]-2-propanol, 2-[((2-amino-2-methylpropyl)amino]-2-methyl-1-propanol, 2-[(4-amino-3-methylbutyl)amino]-2-methyl-1-propanol, 17-amino-3,6,9,12,15-pentaazaheptadecan-1-ol and 3,7,12,16-tetraazaoctadecane-1,18-diol.

29. The method of claim 22 , wherein the polymer matrix comprises at least one selected from the group consisting of: hydrophilic polyacrylates, co-polymers of carboxymethylcellulose and acrylic acid, poly(acrylic acid), poly(acrylic acid) derivatives, acrylic acid copolymers, methacrylic acid, methacrylic acid derivatives, and methacrylic acid copolymers.

30. 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

Assignees

• Novan Inc

Inventors

• Stasko Nathan
• Bauman Susanne
• Joshi Pranav R

Classifications

• A61L2300/45

  Mixtures of two or more drugs, e.g. synergistic mixtures · CPC title

• A61L2300/602

  Type of release, e.g. controlled, sustained, slow · CPC title

• A61L2300/114

  Nitric oxide, i.e. NO · CPC title

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• A61L15/425

  Porous materials, e.g. foams or sponges · CPC title