# US 4,399,123 A · Fibrous tissue dressing or implant

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- Number: US 4,399,123 A
- Document ID: US4399123A
- Status: Granted
- Kind: A
- Application number: 06/221,048
- Filed: 1980-12-29
- Granted: 1983-08-16
- Earliest claimed: 1979-05-29
- Inventors: Roy F. Oliver; Roy A. Grant
- Web page: https://patentgrep.com/patent/US4399123A

## CPC

- A61L 27/362: {Skin, e.g. dermal papillae}
- A61F 2/08: Muscles; Tendons; Ligaments
- A61F 2/10: Hair or skin implants
- A61F 2/30: Joints
- A61K 35/32: Bones; Osteocytes; Osteoblasts; Tendons; Tenocytes; Teeth; Odontoblasts; Cartilage; Chondrocytes; Synovial membrane
- A61K 35/36: Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells (islets of Langerhans A61K35/39)
- A61L 15/40: containing ingredients of undetermined constitution or reaction products thereof {, e.g. plant or animal extracts}
- A61L 27/36: containing ingredients of undetermined constitution or reaction products thereof {, e.g. transplant tissue, natural bone, extracellular matrix (isolated natural compounds, e.g. collagen A61L27/24)}
- A61L 27/3687: {characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents}
- A61L 27/60: Materials for use in artificial skin
- 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)
- A61F: FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS (dental prosthetics A61C)
- 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)

## Abstract

A fibrous tissue preparation suitable for homo or heterotransplantation is obtained by treating mammalian fibrous tissue with a proteolytic enzyme followed, if desired, by further treatment with a carbohydrate splitting enzyme.

## Claims

### Claim 1

A fibrous tissue preparation of mammalian dermal origin which is suitable for homo or heterotransplantation for the permanent repair of or as temporary dressing for cutaneous wounds and soft tissue injuries, which preparation is substantially free of nonfibrous tissue proteins and antigenic polysaccharides, mucopolysaccharides, and glycoproteins.

### Claim 2 (depends on 1)

A fibrous tissue preparation according to claim 1, wherein the mammal is a human or pig.

### Claim 3 (depends on 1)

A process for the preparation of a fibrous tissue according to claim 1, which comprises treating below 20.degree. C. a fibrous tissue of mammalian origin with a proteolytic enzyme selected from the group consisting of pepsin, trypsin, chymotrypsin, ficin, and papain, which will, under the conditions of the process, remove non-fibrous tissue proteins, and further treating said fibrous tissue with a carbohydrate-splitting enzyme, selected from the group consisting of amylase, hyaluronidase, and neuramidinase, which will, under the conditions of the process, remove antigenic polysaccharides, mucopolysaccharides and glycoproteins from said fibrous tissue.

### Claim 4 (depends on 3)

A process according to claim 3 in which the fibrous tissue is treated with both the proteolytic and carbohydrate-splitting enzymes, wherein substantially all of the proteolytic enzyme is removed from said fibrous tissue before treating said fibrous tissue with the carbohydrate-splitting enzyme.

### Claim 5 (depends on 3)

A process according to claim 3, wherein the proteolytic enzyme is trypsin.

### Claim 6 (depends on 3)

A process according to claim 3, wherein prior to the first enzyme treatment the fibrous tissue is contacted with a cold aqueous sodium chloride solution.

### Claim 7 (depends on 3)

A process according to claim 3 which further comprises the step of treating the fibrous tissue with a cross-linking agent, selected from the group consisting of glutaraldehyde, formaldehyde, or nitrous acid, which forms a link between the terminal amino groups of the lysine groups in the fibrous tissue, and under the conditions of the process removes any antigenicity from the tissue.

### Claim 8 (depends on 7)

A process according to claim 7 wherein the further treatment with the cross-linking agent comprises:
(1) treating the tissue with a formaldehyde or glutaraldehyde solution having a strength of more than 0.01% by weight; and
(2) washing the tissue to remove therefrom free formaldehyde, any reversibly bound formaldehyde, and free glutaraldehyde;
such that the resulting fibrous tissue preparation, after its sterilization, will not invoke foreign body reactions and will become vascularized in a recipient.

### Claim 9 (depends on 8)

A process as claimed in claim 8, in which the fibrous tissue is treated with said proteolytic enzyme, and, before the fibrous tissue is treated with said carbohydrate-splitting enzyme, all or substantially all, of said proteolytic enzyme is removed therefrom.

### Claim 10 (depends on 9)

A process as claimed in claim 9, in which the fibrous tissue is treated in the presence of both enzymes, the process conditions being so chosen that when one of said enzymes is active, the other is inactive.

### Claim 11 (depends on 8)

A process as claimed in claim 8, in which said formaldehyde solution has a strength of more than 0.01% and not more than 10%.

### Claim 12 (depends on 8)

A process as claimed in claim 8, in which said glutaraldehyde solution has a strength of from 0.1% to 1.0%.

### Claim 13 (depends on 7)

A fibrous tissue preparation which has been provided by the process of claim 7.

### Claim 14 (depends on 8)

A fibrous tissue preparation which has been prepared by the process of claim 8.

### Claim 15 (depends on 14)

A tissue preparation which is suitable as a cleansing agent for cutaneous wounds and soft tissue injuries and which has been provided by sterilizing, lyophilizing and powdering a fibrous tissue preparation as claimed in claim 14.
