# US 10,441,664 B2 · Cross-linked collagen with at least one bound antimicrobial agent for in vivo release of the agent

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- Number: US 10,441,664 B2
- Document ID: US10441664B2
- Status: Granted
- Kind: B2
- Application number: 14/879,551
- Filed: 2015-10-09
- Published: 2016-06-30
- Granted: 2019-10-15
- Earliest claimed: 2012-11-19
- Assignees: MiMedx Group, Inc.
- Applicants: MiMedx Group, Inc.
- Inventors: Thomas J. Koob
- Web page: https://patentgrep.com/patent/US10441664B2

## CPC

- A61K 47/6435: {the peptide or protein in the drug conjugate being a connective tissue peptide, e.g. collagen, fibronectin or gelatin}
- A61K 8/19: containing inorganic ingredients
- A61K 8/65: Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
- A61K 9/0024: {Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue (compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L)}
- A61K 33/38: Silver; Compounds thereof
- A61K 38/39: Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61L 27/24: Collagen
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61Q 17/005: {Antimicrobial preparations}
- A61K 2800/51: Chelating agents
- A61L 2300/104: Silver, e.g. silver sulfadiazine
- A61L 2300/404: Biocides, antimicrobial agents, antiseptic agents
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS

## Abstract

The disclosure describes collagen constructs comprising antimicrobial agents and related methods.

## Claims

### Claim 1

An antimicrobial cross-linked collagen construct comprising:
a cross-linked collagen comprising collagen and one or more cross-linking agents and an antimicrobial amount of silver incorporated into the construct, wherein at least a portion of the silver is incorporated into the cross-linked collagen by chelation at least in part through a cross-linking agent, and wherein the one or more cross-linking agents comprise a 1,2-benzoquinone moiety, a 1,2-dihydroxyphenyl moiety, 3,4-dihydroxyphenylalanine, dopamine, 3,4-dihydroxybenzaldehyde, or 3,4-dihydroxybenzoic acid; and
wherein the collagen has not been stabilized by treatment with ultraviolet radiation.

### Claim 2 (depends on 1)

The construct of claim 1, wherein the one or more cross-linking agents comprise a 1,2-benzoquinone moiety and/or a 1,2-dihydroxyphenyl moiety.

### Claim 3 (depends on 2)

The construct of claim 2, wherein the silver is ionic silver which is bound at least in part to the 1,2-benzoquinone moiety and/or the 1,2-dihydroxyphenyl moiety.

### Claim 4 (depends on 1)

The construct of claim 1, wherein the silver comprises ionic silver selected from the group consisting of silver (I) and/or silver (II).

### Claim 5 (depends on 4)

The construct of claim 4, wherein the ionic silver comprises silver chloride, silver phosphate, silver sulfate, silver acetate, silver nitrate, silver fluoride, silver iodide, silver lactate, silver benzoate, silver bromide, silver carbonate, silver citrate, silver iodate, silver laurate, silver oxide, silver palmitate, silver protein, silver imidazolate, arglaes, colloidal silver, silver crystals, silver nanocrystals, silver plating, and/or silver sulfonamides.

### Claim 6 (depends on 1)

The construct of claim 1, wherein the silver incorporated into the construct is present in an amount of between about 0.1% to about 30%.

### Claim 7 (depends on 1)

The construct of claim 1, wherein some or all of the antimicrobial amount of silver is released in vivo in contact with an aqueous medium.

### Claim 8 (depends on 1)

The construct of claim 1, wherein the antimicrobial cross-linked collagen construct provides a sustained release of silver, wherein the sustained release comprises a plurality of release rates including an immediate release, an intermediate release, an extended release or any combination of release rates thereof.

### Claim 9 (depends on 8)

The construct of claim 8, wherein an effective amount of silver is released from about 1 minute to about 60 days after implantation, or any range therein.

### Claim 10 (depends on 1)

The construct of claim 1, wherein the collagen is a gel.

### Claim 11 (depends on 1)

The construct of claim 1, wherein the collagen is a film which coats a collagen fiber.