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

Patent metadata

Field	Value
Publication number	US-9713652-B2
Application number	US-201313975930-A
Country	US
Kind code	B2
Filing date	Aug 26, 2013
Priority date	Feb 28, 2011
Publication date	Jul 25, 2017
Grant date	Jul 25, 2017

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.

First claim

We claim:

1. S-nitrosothiol-functionalized co-condensed silica particles having an NO storage in a range of about 0.01 μmol to about 10 μmol 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 μmol to about 4.40 μmol 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:

wherein R, R′ and R″ are each independently alkyl and n is in a range of 0 to 10.

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.

Assignees

• Novan Inc
• Univ North Carolina Chapel Hill

Inventors

• Schoenfisch Mark
• Riccio Daniel
• Nugent Julia
• Stasko Nathan

Classifications

• Y10T428/2982

  Particulate matter [e.g., sphere, flake, etc.] · CPC title

• C08G77/26

  nitrogen-containing groups · CPC title

• C07F7/0874 Primary

  Reactions involving a bond of the Si-O-Si linkage · CPC title

• C07F7/1804

  Compounds having Si-O-C linkages (Si-O-acyl linkages C07F7/1896) · CPC title

• C08K2003/023

  Silicon · CPC title