Nitric oxide-releasing S-nitrosothiol-modified silica particles and methods of making the same

• US 9,713,652 B2
• Filed: 08/26/2013
• Issued: 07/25/2017
• Est. Priority Date: 02/28/2011
• Status: Active Grant

• Current Assignee: LNHC Incorporated, University of North Carolina At Chapel Hill (University of North Carolina System)
• Original Assignee: Novan, Inc., University of North Carolina At Chapel Hill (University of North Carolina System)
• Inventors: Schoenfisch, Mark, Riccio, Daniel, Stasko, Nathan, Nugent, Julia
• Primary Examiner(s): Le, Holly
• Application Number:
  US13/975,930
• Publication Number:
  US 20130344334A1
• Time in Patent Office: 1,429 Days
• Field of Search: 436107, 436119, 436527, 428403-405
• CPC Class Codes: A61L 2/18 Liquid substances or solutions comprising solids or dissolved gases
• CPC Class Codes: C07F 7/0874 Reactions involving a bond of the Si-O-Si linkage
• CPC Class Codes: C07F 7/10 containing nitrogen having a Si-N linkage
• CPC Class Codes: C07F 7/1804 Compounds having Si-O-C linkages Si-O-acyl linkages C07F7/1896
• CPC Class Codes: C08G 77/26 nitrogen-containing groups
• CPC Class Codes: C08G 77/28 sulfur-containing groups
• CPC Class Codes: C08K 2003/023 Silicon
• CPC Class Codes: C08K 3/28 Nitrogen-containing compounds
• CPC Class Codes: C08K 3/30 Sulfur-, selenium- or tellurium-containing compounds
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]

Abstract

Provided according to some embodiments of the invention are methods of forming co-condensed silica particles. In some embodiments, the methods include reacting a thiol-containing silane and a backbone alkoxysilane in a reaction solution that comprises water to form thiol-functionalized co-condensed silica particles, wherein the thiol-functionalized co-condensed silica particles include a polysiloxane matrix and at least some of thiol groups are present within the polysiloxane matrix; and reacting the thiol-functionalized co-condensed silica particles with a nitrosating agent to provide the S-nitrosothiol-functionalized co-condensed silica particles. In some embodiments, provided are S-nitrosothiol-functionalized co-condensed silica particles.

Claims

1. S-nitrosothiol-functionalized co-condensed silica particles having an NO storage in a range of about 0.01 μ

mol to about 10 μ

mol NO per mg particle.

2. The S-nitrosothiol-functionalized co-condensed silica particles of claim 1, wherein the particles have an NO storage in a range of about 0.09 μ

mol to about 4.40 μ

mol NO per mg particle.

3. The S-nitrosothiol-functionalized co-condensed silica particles of claim 1, wherein the particles comprise a polysiloxane matrix and have at least some nitrosothiol functional groups distributed within the polysiloxane matrix.

4. The S-nitrosothiol-functionalized co-condensed silica particles of claim 1, wherein the S-nitrosothiol functional groups comprise primary nitrosothiol functional groups.

5. The S-nitrosothiol-functionalized co-condensed silica particles of claim 1, wherein the S-nitrosothiol functional groups comprise tertiary nitrosothiol functional groups.

6. S-nitrosothiol-functionalized monodisperse co-condensed silica particles having an average particle diameter in a range of about 200 nm to about 700 nm.

7. The S-nitrosothiol-functionalized co-condensed silica particles of claim 6, wherein the particles comprise a polysiloxane matrix and have at least some nitrosothiol functional groups distributed within the polysiloxane matrix.

8. The S-nitrosothiol-functionalized co-condensed silica particles of claim 6, wherein the S-nitrosothiol functional groups comprise primary nitrosothiol functional groups.

9. The S-nitrosothiol-functionalized co-condensed silica particles of claim 6, wherein the S-nitrosothiol functional groups comprise tertiary nitrosothiol functional groups.

10. The S-nitrosothiol-functionalized co-condensed silica particles of claim 6, wherein the particles are formed from the condensation of a thiol-containing silane and a backbone alkoxysilane.

11. The S-nitrosothiol-functionalized co-condensed silica particles of claim 10, wherein the thiol-containing silane is a tertiary thiol-containing silane.

12. A method of forming the S-nitrosothiol-functionalized monodisperse co-condensed silica particles of claim 6, the method comprising:

reacting a thiol-containing silane and a backbone alkoxysilane in a sol precursor solution that comprises water to form thiol-functionalized co-condensed silica particles, wherein the thiol-functionalized co-condensed silica particles comprise a polysiloxane matrix and at least some of thiol groups are present within the polysiloxane matrix; and

reacting the thiol-functionalized co-condensed silica particles with a nitrosating agent to provide the S-nitrosothiol-functionalized monodisperse co-condensed silica particles.

13. The method of claim 12, wherein the thiol-containing silane comprises a primary thiol-containing silane.

14. The method of claim 13, wherein the primary thiol-containing silane is mercaptopropyltrimethoxysilane and the backbone alkoxysilane is tetraethoxysilane.

15. The method of claim 13, wherein the primary thiol-containing silane comprises mercaptopropyltrimethoxysilane and the backbone alkoxysilane comprises tetramethoxysilane.

16. The method of claim 15, wherein the sol precursor solution comprises an ammonia catalyst at a concentration in a range of about 1.9 to about 5.5 M;

wherein the total silane monomer concentration in the sol precursor solution is in a range of about 0.1 M to about 0.4 M;

wherein the total silane monomer concentration comprises about 25 to about 85 mol % mercaptopropyltrimethoxysilane; and

wherein the water is present in the sol precursor solution at a concentration in a range of about 8.0 to about 32.5 M.

17. The method of claim 12, wherein the thiol-containing silane comprises a tertiary thiol-containing silane.

18. The method of claim 17, wherein the tertiary thiol-containing silane comprises a tertiary thiol having the following structure:

19. The method of claim 18, wherein the tertiary thiol-containing silane has the following structure:

20. The method of claim 18, wherein the backbone alkoxysilane comprises tetraethoxysilane.

21. The method of claim 12, wherein the thiol-functionalized co-condensed silica particles are sonicated prior to reacting the thiol-functionalized co-condensed silica particles with a nitrosating agent.