# US 11,110,206 B2 · Silk sericin-based hydrogel, methods 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 11,110,206 B2
- Document ID: US11110206B2
- Status: Granted
- Kind: B2
- Application number: 16/317,051
- Filed: 2017-07-12
- Published: 2019-07-25
- Granted: 2021-09-07
- Earliest claimed: 2016-07-12
- Assignees: Universidade CatóLica Portuguesa
- Applicants: Universidade CatóLica Portuguesa
- Inventors: Ana Leite De Almeida Monteiro De Oliveira; Sara Isabel Macedo Baptista Da Silva; Sandra Cristina Ferreira Borges; Paulo Jorge Pereira Alves
- Web page: https://patentgrep.com/patent/US11110206B2

## CPC

- A61L 27/52: Hydrogels or hydrocolloids
- A61L 15/44: Medicaments
- A61L 15/48: Surfactants
- A61L 15/58: Adhesives
- A61L 15/60: Liquid-swellable gel-forming materials, e.g. super-absorbents
- A61L 15/64: specially adapted to be resorbable inside the body
- A61L 26/0047: {Specific proteins or polypeptides not covered by groups A61L26/0033 - A61L26/0042}
- A61L 26/0066: {Medicaments; Biocides}
- A61L 26/008: {Hydrogels or hydrocolloids}
- A61L 27/227: {Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24}
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- C08J 3/075: Macromolecular gels
- A61L 2300/102: Metals or metal compounds, e.g. salts such as bicarbonates, carbonates, oxides, zeolites, silicates
- A61L 2300/204: with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
- A61L 2300/232: Monosaccharides, disaccharides, polysaccharides, lipopolysaccharides
- A61L 2300/254: Enzymes, proenzymes
- A61L 2300/406: Antibiotics
- A61L 2300/42: Anti-thrombotic agents, anticoagulants, anti-platelet agents
- A61L 2300/802: Additives, excipients, e.g. cyclodextrins, fatty acids, surfactants
- A61L 2400/04: Materials for stopping bleeding
- A61L 2400/06: Flowable or injectable implant compositions
- A61L 2430/06: for cartilage reconstruction, e.g. meniscus
- A61L 2430/24: for joint reconstruction
- A61L 2430/34: for soft tissue reconstruction
- C08J 2389/00: Characterised by the use of proteins; Derivatives thereof
- 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)
- C08J: WORKING-UP; GENERAL PROCESSES OF COMPOUNDING; AFTER-TREATMENT NOT COVERED BY SUBCLASSES C08B, C08C, C08F, C08G or C08H (working, e.g. shaping, of plastics B29)

## Abstract

The present disclosure relates to a novel sericin-based hydrogel wherein the silk sericin is enzymatically cross-linked for an improved treatment of wound healing, ischemic diseases or cardiovascular diseases, namely chronic wound healing, in particular diabetic wound.

## Claims

### Claim 1

A hydrogel comprising:
at least 4% (w/v) of an enzymatically cross-linked silk sericin,
wherein the silk sericin is enzymatically cross-linked by an enzyme complex selected from the group consisting of: horseradish peroxidase and hydrogen peroxide, laccase, transglutaminase, and mixtures thereof;
wherein a cross-section of said hydrogel has pores with a diameter between 50-100 μm, and;
wherein the hydrogel is suitable for medicinal applications, veterinary applications, cosmetic applications or as an in vitro model for cell culture studies.

### Claim 2 (depends on 1)

The hydrogel of claim 1, wherein the hydrogel comprises at least 7.5% (w/v) of silk sericin.

### Claim 3 (depends on 1)

The hydrogel of claim 1, comprising 4-20% (w/v) of an enzymatically cross-linked silk sericin.

### Claim 4 (depends on 1)

The hydrogel of claim 1, comprising 6-7.5% (w/v) of an enzymatically cross-linked silk sericin.

### Claim 5 (depends on 1)

The hydrogel of claim 1, wherein the silk sericin is enzymatically cross-linked by horseradish peroxidase and hydrogen peroxide for 10 seconds-5 minutes.

### Claim 6 (depends on 1)

The hydrogel of claim 1, wherein the silk sericin is enzymatically cross-linked with 0.1-0.6% (w/v) of horseradish peroxidase and 0.15-0.4% (v/v) of hydrogen peroxide.

### Claim 7 (depends on 1)

The hydrogel of claim 1, wherein the silk sericin has a molecular weight of 150-400 kDa.

### Claim 8 (depends on 1)

The hydrogel of claim 1, wherein said hydrogel has an antioxidant activity of 0.03-0.05 eq [Asc. Ac.]g/L)/g.

### Claim 9 (depends on 1)

The hydrogel of claim 1, further comprising a biological active agent, a therapeutic agent, an additive, a pharmaceutically acceptable excipient, a pharmaceutically acceptable carrier, and mixtures thereof.

### Claim 10 (depends on 9)

The hydrogel of claim 9, wherein the additive is a surfactant selected from the following list: polysorbates, cationic molecules or polymers, and mixtures thereof.

### Claim 11 (depends on 9)

The hydrogel of claim 9, wherein the additive is polysorbate 20, polysorbate 80 or poly-lysine.

### Claim 12 (depends on 9)

The hydrogel of claim 9, wherein the biological active agent or the therapeutic agent is selected from the following list: antibiotic, coagulation agent, cell, stem cell, ligand, growth factor, platelet, and mixtures thereof.

### Claim 13 (depends on 12)

The hydrogel of claim 12, wherein the antibiotic is vancomycin, streptomycin, ciprofloxacin, or mixtures thereof.

### Claim 14 (depends on 12)

The hydrogel of claim 12, wherein the coagulation agent is thrombin or calcium.

### Claim 15 (depends on 1)

The hydrogel of claim 1, wherein the hydrogel is transparent.

### Claim 16 (depends on 1)

The hydrogel of claim 1, wherein the hydrogel is an injectable hydrogel or a topical hydrogel.

### Claim 17 (depends on 1)

An adhesive or a patch comprising the hydrogel of claim 1.

### Claim 18 (depends on 1)

A method for producing the hydrogel of claim 1, comprising the following steps:
extracting silk sericin by immersing cocoons in water, at 100° C. for 40-60 min, in a ratio of 1-3% weight cocoons/volume of water;
filtering the silk sericin;
concentrating the silk sericin to at least 4% (w/v);
preparing the hydrogel by adding 0.2% (w/v) of horseradish peroxidase, 0.3% (v/v) hydrogen peroxide and at least 4% (w/v) of silk sericin to water to form a mixture; and
mixing the mixture for at least 10 seconds.