# US 11,897,775 B2 · Mesoporous nitric oxide-releasing silica particles, methods of making, and uses thereof

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,897,775 B2
- Document ID: US11897775B2
- Status: Granted
- Kind: B2
- Application number: 17/399,634
- Filed: 2021-08-11
- Published: 2021-12-09
- Granted: 2024-02-13
- Earliest claimed: 2017-08-01
- Assignees: University of Georgia Research Foundation, Inc.
- Applicants: University of Georgia Research Foundation, Inc.
- Inventors: Hitesh Handa; Marcus Goudie; Jitendra Pant; Bryan Grommersch; Sean Hopkins
- Web page: https://patentgrep.com/patent/US11897775B2

## CPC

- C01B 33/149: Coating
- A61L 27/28: Materials for coating prostheses
- A61L 27/306: {Other specific inorganic materials not covered by A61L27/303 - A61L27/32}
- A61L 27/3637: {characterised by the origin of the biological material other than human or animal, e.g. plant extracts, algae}
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 27/56: Porous materials, {e.g. foams or sponges}
- A61L 29/08: Materials for coatings
- A61L 29/106: {Inorganic materials other than carbon}
- A61L 29/146: {Porous materials, e.g. foams or sponges}
- A61L 29/16: Biologically active materials, e.g. therapeutic substances {(A61L29/048 takes precedence)}
- A61L 31/08: Materials for coatings
- A61L 31/088: {Other specific inorganic materials not covered by A61L31/084 or A61L31/086}
- A61L 31/146: {Porous materials, e.g. foams or sponges}
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- C07K 16/10: RNA viruses
- C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes}
- C12N 9/0065: {acting on hydrogen peroxide as acceptor (1.11)}
- G01N 33/543: with an insoluble carrier for immobilising immunochemicals
- A61L 2300/114: Nitric oxide, i.e. NO
- A61L 2420/04: Coatings containing a composite material such as inorganic/organic, i.e. material comprising different phases
- C01P 2002/82: by IR- or Raman-data
- C01P 2004/03: obtained by SEM
- C01P 2004/61: Micrometer sized, i.e. from 1-100 micrometer
- C01P 2006/16: Pore diameter
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/565: Complementarity determining region [CDR]
- C12Y 111/01007: Peroxidase (1.11.1.7), i.e. horseradish-peroxidase
- G01N 2333/165: Coronaviridae, e.g. avian infectious bronchitis virus
- C01B: NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; {METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C}
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- C01P: INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
- C12Y: ENZYMES

## Abstract

Nitric oxide-releasing materials, methods of making nitric oxide-releasing materials, and uses of nitric oxide-releasing materials are provided. The nitric oxide-releasing materials include a mesoporous silica core and an outer surface having a plurality of nitric oxide donors. In an exemplary aspects, the nitric oxide-releasing material includes a mesoporous diatomaceous earth core, and an outer surface having a plurality of S-nitroso-N-acetyl-penicillamine groups covalently attached thereto. Uses of the nitric oxide-releasing materials can include coatings for medical devices such as catheters, grafts, and stents; wound gauzes; acne medications; and antiseptic mouthwashes; among others.

## Claims

### Claim 1

A nitric oxide-releasing material consisting of:
a mesoporous silica core having an outer surface, and
a plurality of moieties having a structure according to the following formula covalently bonded to the outer surface of the mesoporous silica core
where A is a S-nitrosothiol selected from the group consisting of S-nitroso-N-acetyl-penicillamine, S-nitroso-N-acetyl cysteine, S-nitroso-N-acetyl cysteamine, S-nitrosoglutathione, and methyl S-nitrosothioglycolate;
where R1 is a substituted or unsubstituted C1-C20 alkyl, a substituted or unsubstituted C1-C20 heteroalkyl, a substituted or unsubstituted C2-C20 alkenyl, a substituted or unsubstituted C2-C20 herteroalkenyl, a substituted or unsubstituted C1-C20 alkoxy, or a substituted or unsubstituted C1-C20 heteroalkoxy;
where each occurrence of R2 is independently a substituted or unsubstituted C1-C20 alkyl, a substituted or unsubstituted C1-C20 heteroalkyl, a substituted or unsubstituted C2-C20 alkenyl, a substituted or unsubstituted C2-C20 herteroalkenyl, a substituted or unsubstituted C1-C20 alkoxy, a substituted or unsubstituted C1-C20 heteroalkoxy, or a bond to an oxygen atom on the outer surface so long as at least one occurrence of R2 is a bond to an oxygen atom on the outer surface of the mesoporous silica core.

### Claim 2 (depends on 1)

The nitric oxide-releasing material according claim 1, wherein R1 is a substituted or unsubstituted C1-C12 alkyl.

### Claim 3 (depends on 1)

The nitric oxide-releasing material according to claim 1, wherein each occurrence of R2 is independently a substituted or unsubstituted C1-C6 alkyl or a bond to an oxygen atom on the outer surface.

### Claim 4 (depends on 1)

The nitric oxide-releasing material according to claim 1, wherein the nitric oxide-releasing material has a nitric oxide content of about 0.025 μmol to about 0.05 μmol per mg of the nitric oxide-releasing material.

### Claim 5 (depends on 1)

The nitric oxide-releasing material according to claim 1, wherein the nitric oxide-releasing material has a half-life for nitric oxide release of about 20 hours to about 40 hours.

### Claim 6 (depends on 1)

The nitric oxide-releasing material according to claim 1, wherein the nitric oxide-releasing material has an average pore size of about 300 nm to about 600 nm.

### Claim 7 (depends on 1)

The nitric oxide-releasing material according claim 1, wherein the nitric oxide-releasing material is a particle having a longest dimension of about 10 μm to about 20 μm.

### Claim 8 (depends on 1)

The nitric oxide-releasing material according to claim 1, wherein the mesoporous silica core is selected from the group consisting of a diatomaceous earth, a rice husk, an SAB-3 type mesoporous silica, an HMS type mesoporous silica, MSU-X type mesoporous silica, an SBA-12 type mesoporous silica, an SBA-15 type mesoporous silica, an SBA-16 type mesoporous silica, and an MCM-41 type mesoporous silica.

### Claim 9 (depends on 1)

The nitric oxide-releasing material according to claim 1, wherein R1 is C1-C3 alkyl.

### Claim 10 (depends on 1)

The nitric oxide-releasing material according to claim 1, wherein R2 is C1-C2 alkyl.

### Claim 11 (depends on 1)

The nitric oxide-releasing material according to claim 1, wherein the plurality of moieties covalently bonded to the outer surface of the mesoporous silica core has the formula

### Claim 12 (depends on 1)

A medical device having at least one surface, wherein the surface comprises the nitric oxide-releasing material having a structure according to claim 1.

### Claim 13 (depends on 12)

The medical device according to claim 12, wherein the medical device is a urinary catheter, a vascular catheter, a graft, a stent, or a hydrogel strip.