CA1110971A - Collagen skin dressing - Google Patents
Collagen skin dressingInfo
- Publication number
- CA1110971A CA1110971A CA304,330A CA304330A CA1110971A CA 1110971 A CA1110971 A CA 1110971A CA 304330 A CA304330 A CA 304330A CA 1110971 A CA1110971 A CA 1110971A
- Authority
- CA
- Canada
- Prior art keywords
- collagen
- gel
- atelocollagen
- sheet
- antibiotics
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 108010035532 Collagen Proteins 0.000 title claims abstract description 71
- 102000008186 Collagen Human genes 0.000 title claims abstract description 71
- 229920001436 collagen Polymers 0.000 title claims abstract description 71
- 239000000499 gel Substances 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 31
- 239000003899 bactericide agent Substances 0.000 claims description 19
- 239000003242 anti bacterial agent Substances 0.000 claims description 18
- 229940088710 antibiotic agent Drugs 0.000 claims description 18
- 230000008569 process Effects 0.000 claims description 17
- 239000000463 material Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 11
- 239000000512 collagen gel Substances 0.000 claims description 10
- 230000015271 coagulation Effects 0.000 claims description 9
- 238000005345 coagulation Methods 0.000 claims description 9
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 claims description 7
- 230000000844 anti-bacterial effect Effects 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 238000004108 freeze drying Methods 0.000 claims description 6
- 235000019271 petrolatum Nutrition 0.000 claims description 5
- 238000001226 reprecipitation Methods 0.000 claims description 5
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical group ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 claims description 4
- 108091005804 Peptidases Proteins 0.000 claims description 4
- 102000035195 Peptidases Human genes 0.000 claims description 4
- 238000007605 air drying Methods 0.000 claims description 4
- 238000001125 extrusion Methods 0.000 claims description 4
- 229940014800 succinic anhydride Drugs 0.000 claims description 4
- 108010045569 atelocollagen Proteins 0.000 claims 22
- 238000004132 cross linking Methods 0.000 claims 8
- 239000000126 substance Substances 0.000 claims 5
- 230000001376 precipitating effect Effects 0.000 claims 3
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 239000006185 dispersion Substances 0.000 claims 1
- 239000011541 reaction mixture Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 8
- 229930182566 Gentamicin Natural products 0.000 description 6
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 6
- 206010052428 Wound Diseases 0.000 description 6
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 229960002518 gentamicin Drugs 0.000 description 6
- 208000015181 infectious disease Diseases 0.000 description 6
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 5
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 5
- 229960003942 amphotericin b Drugs 0.000 description 5
- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 description 5
- 229960005287 lincomycin Drugs 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- BPKIGYQJPYCAOW-FFJTTWKXSA-I calcium;potassium;disodium;(2s)-2-hydroxypropanoate;dichloride;dihydroxide;hydrate Chemical compound O.[OH-].[OH-].[Na+].[Na+].[Cl-].[Cl-].[K+].[Ca+2].C[C@H](O)C([O-])=O BPKIGYQJPYCAOW-FFJTTWKXSA-I 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 229910001961 silver nitrate Inorganic materials 0.000 description 4
- LMEWRZSPCQHBOB-UHFFFAOYSA-M silver;2-hydroxypropanoate Chemical compound [Ag+].CC(O)C([O-])=O LMEWRZSPCQHBOB-UHFFFAOYSA-M 0.000 description 4
- 230000029663 wound healing Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 3
- 102000057297 Pepsin A Human genes 0.000 description 3
- 108090000284 Pepsin A Proteins 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000003792 electrolyte Substances 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 229940111202 pepsin Drugs 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 206010040844 Skin exfoliation Diseases 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- RRDRHWJDBOGQHN-JWCTVYNTSA-N [2-[(2s,5r,8s,11s,14r,17s,22s)-17-[(1r)-1-hydroxyethyl]-22-[[(2s)-2-[[(2s,3r)-3-hydroxy-2-[[(2s)-2-[6-methyloctanoyl(sulfomethyl)amino]-4-(sulfomethylamino)butanoyl]amino]butyl]amino]-4-(sulfomethylamino)butanoyl]amino]-5,8-bis(2-methylpropyl)-3,6,9,12,15 Chemical compound CCC(C)CCCCC(=O)N(CS(O)(=O)=O)[C@@H](CCNCS(O)(=O)=O)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCNCS(O)(=O)=O)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](CCNCS(O)(=O)=O)NC(=O)[C@H](CCNCS(O)(=O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCNCS(O)(=O)=O)NC1=O RRDRHWJDBOGQHN-JWCTVYNTSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 229940108538 colistimethate Drugs 0.000 description 2
- 108700028201 colistinmethanesulfonic acid Proteins 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 description 2
- 235000019800 disodium phosphate Nutrition 0.000 description 2
- 230000001788 irregular Effects 0.000 description 2
- 229930027917 kanamycin Natural products 0.000 description 2
- 229960000318 kanamycin Drugs 0.000 description 2
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 2
- 229930182823 kanamycin A Natural products 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000002791 soaking Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241001550206 Colla Species 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 108010059712 Pronase Proteins 0.000 description 1
- 206010072170 Skin wound Diseases 0.000 description 1
- 206010053615 Thermal burn Diseases 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000000515 collagen sponge Substances 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 210000002310 elbow joint Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical class O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
- 230000035322 succinylation Effects 0.000 description 1
- 238000010613 succinylation reaction Methods 0.000 description 1
- 230000036575 thermal burns Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/32—Proteins, polypeptides; Degradation products or derivatives thereof, e.g. albumin, collagen, fibrin, gelatin
- A61L15/325—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/425—Porous materials, e.g. foams or sponges
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
- A61L2300/406—Antibiotics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Materials Engineering (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Dermatology (AREA)
- Communicable Diseases (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE
Skin or wound dressings are prepared in gel or film form from collagen and/or chemically modified collagen.
Skin or wound dressings are prepared in gel or film form from collagen and/or chemically modified collagen.
Description
7~
This invention relates to skin dressings consisting of collagen or chemically modified collagen in gel form, in porous sheet form or in semiporous film type form. The invention also relates to the production of such skin dressings by preparation of sterile succinylated collagen gel, and by preparation of collagen porous sheet made by successive processes of extrusion of collagen gel into coagulation bath, tanning with glutaraldehyde, and/or partial air-drying followed by freeze-drying. Bactericidal agents or antibiotics may be impregnated into the gel or sheet-type dressing.
A number of investigators including the present inventors ~; have suggested the use of collagen material as a skin, burn or wound dressing. The feature of this invention, however, ; consists in the form of the collagen dressing and in the method of producing such desired types.
The National Fire Protection Association reported in 1962 that approximately l,800~000 persons sustain burns yearly and occupy over ll,000 hospital beds per day. There is a great need for a readily available, easily stored and temporary substitute for human skin for the effective treatment of thermal burns and other forms of skin loss. It is common practice to cover skin loss area with split-thickness autografts, homografts and heterografts. Such treatments protect against ` infection, the loss of protein, fluid and electrolytes from exposed tissue. These treatments, however have the following drawbacks. Grafts are difficult to obtain, and to store for any prolonged period of time and also are quite expensive.
These difficulties could be reduced by the development of artificial skin dressings which are inexpensive and readily available to use.
.
:
37~
Collagen is a major protein of connect tissue such as skin, cornea, etc. and can be solubilized, separated and purified by the treatment with proteolytic enzymes (other than collagenase), e.g., proctase, pepsin, trypsin and pronase.
Solubilized collagen is telopeptides-poor, relatively inexpensive and ideal as a material for development into a skin wound dressing.
Solubilized collagen has many NH2 and COOH groups in its structure, and chemical modifications of the molecule can be readily made, e.g., all or some of the amino groups may be acylated by reaction with a mixture of acetic anhydride and acetic acid. Similarly, succinic anhydride reacts with collagen replacing amino groups by carboxyl groups. The carboxyl groups contained in the molecule are susceptible to esterification by the standard reaction with acidified alochol, e.g., reaction with anhydrous methanol acidified with HCl. In the above reactions the net isoelectric point of collagen can - be controlled, either negative or positive, or completely neutralized.
All known types of collagen and chemically modified collagen may be employed in the practice of this invention e.g., native, denatured collagen (neutral isoelectric point);
esterified collagen (alkaline isoelectric point) and modified amino-group forms e.g., anhydride derivatives (acidic lsoelectric point). In the preparation of gel type dressings of this invention the use of anhydride derivatives (acidic isoelectric point) e.g., succinic anhydride derivatives of collagen are preferred.
Gel Type The gel type skin dressings of this invention are especially suitable for application to irregular body surfaces
This invention relates to skin dressings consisting of collagen or chemically modified collagen in gel form, in porous sheet form or in semiporous film type form. The invention also relates to the production of such skin dressings by preparation of sterile succinylated collagen gel, and by preparation of collagen porous sheet made by successive processes of extrusion of collagen gel into coagulation bath, tanning with glutaraldehyde, and/or partial air-drying followed by freeze-drying. Bactericidal agents or antibiotics may be impregnated into the gel or sheet-type dressing.
A number of investigators including the present inventors ~; have suggested the use of collagen material as a skin, burn or wound dressing. The feature of this invention, however, ; consists in the form of the collagen dressing and in the method of producing such desired types.
The National Fire Protection Association reported in 1962 that approximately l,800~000 persons sustain burns yearly and occupy over ll,000 hospital beds per day. There is a great need for a readily available, easily stored and temporary substitute for human skin for the effective treatment of thermal burns and other forms of skin loss. It is common practice to cover skin loss area with split-thickness autografts, homografts and heterografts. Such treatments protect against ` infection, the loss of protein, fluid and electrolytes from exposed tissue. These treatments, however have the following drawbacks. Grafts are difficult to obtain, and to store for any prolonged period of time and also are quite expensive.
These difficulties could be reduced by the development of artificial skin dressings which are inexpensive and readily available to use.
.
:
37~
Collagen is a major protein of connect tissue such as skin, cornea, etc. and can be solubilized, separated and purified by the treatment with proteolytic enzymes (other than collagenase), e.g., proctase, pepsin, trypsin and pronase.
Solubilized collagen is telopeptides-poor, relatively inexpensive and ideal as a material for development into a skin wound dressing.
Solubilized collagen has many NH2 and COOH groups in its structure, and chemical modifications of the molecule can be readily made, e.g., all or some of the amino groups may be acylated by reaction with a mixture of acetic anhydride and acetic acid. Similarly, succinic anhydride reacts with collagen replacing amino groups by carboxyl groups. The carboxyl groups contained in the molecule are susceptible to esterification by the standard reaction with acidified alochol, e.g., reaction with anhydrous methanol acidified with HCl. In the above reactions the net isoelectric point of collagen can - be controlled, either negative or positive, or completely neutralized.
All known types of collagen and chemically modified collagen may be employed in the practice of this invention e.g., native, denatured collagen (neutral isoelectric point);
esterified collagen (alkaline isoelectric point) and modified amino-group forms e.g., anhydride derivatives (acidic lsoelectric point). In the preparation of gel type dressings of this invention the use of anhydride derivatives (acidic isoelectric point) e.g., succinic anhydride derivatives of collagen are preferred.
Gel Type The gel type skin dressings of this invention are especially suitable for application to irregular body surfaces
- 2 -97~
e.g., areas of the joints, elbows, knees, etc. The gel dressing is preferably used in the form of a viscous paste of petroleum jelly consistency and contains 1 - 10%, preferably 2 - 5~ of collagen.
In the preparation of the collagen gel, skin or hide is solubilized in an enzyme solution at acidic pH. The resulting gel is a viscous material which is recovered by filtering, e.g., through cheese cloth and/or a millipore filter. The viscous solution is made alkaline by addition of caustic to a pH of about 10. At this stage the material is permitted to stand in order to inactivate any remaining enzyme. The material is thereafter neutralized, the collagen collected by centrifuge and washed with water. A second purification step follows, namely, redissolving in aqueous acid (pH 2.0 - 5.0), reprecipi-tation by neutralization to a pH of 6 to 7, and purification to remove acid by dialysis against water. The neutral gel is recovered and at this stage antibiotics or bactericides or both may be added before storage of the gel material.
Collagen material used in the preparation of gel is preferably not a multimer and, therefore, the material is not - subjected to tanning during its preparation.
Succinylated collagen was preferably used for making viscous gel skin dressing since it can be redissolved in water at physiologic pH (6.8 - 7.4) without requiring dialysis against water to remove acid during its preparation. Collagen concentra-tion of gel skin dressing was between 0.5% to 7~ and into it was incorporated the following bactericidal agents: Silver nitrate solution (0.5 g/100 ml) or silver lactate solution (9.5 g/100 ml) 25 mg/ml Lincomycin, 5 mg/ml Amphotericin B
and 25 mg/ml Gentamicin, or one or more thereof.
, .
g~l Pourous Sheet Type Another type of collagen skin dressing (porous sheet) was prepared as follows: Solubilized collagen gel (pH 2.0 -
e.g., areas of the joints, elbows, knees, etc. The gel dressing is preferably used in the form of a viscous paste of petroleum jelly consistency and contains 1 - 10%, preferably 2 - 5~ of collagen.
In the preparation of the collagen gel, skin or hide is solubilized in an enzyme solution at acidic pH. The resulting gel is a viscous material which is recovered by filtering, e.g., through cheese cloth and/or a millipore filter. The viscous solution is made alkaline by addition of caustic to a pH of about 10. At this stage the material is permitted to stand in order to inactivate any remaining enzyme. The material is thereafter neutralized, the collagen collected by centrifuge and washed with water. A second purification step follows, namely, redissolving in aqueous acid (pH 2.0 - 5.0), reprecipi-tation by neutralization to a pH of 6 to 7, and purification to remove acid by dialysis against water. The neutral gel is recovered and at this stage antibiotics or bactericides or both may be added before storage of the gel material.
Collagen material used in the preparation of gel is preferably not a multimer and, therefore, the material is not - subjected to tanning during its preparation.
Succinylated collagen was preferably used for making viscous gel skin dressing since it can be redissolved in water at physiologic pH (6.8 - 7.4) without requiring dialysis against water to remove acid during its preparation. Collagen concentra-tion of gel skin dressing was between 0.5% to 7~ and into it was incorporated the following bactericidal agents: Silver nitrate solution (0.5 g/100 ml) or silver lactate solution (9.5 g/100 ml) 25 mg/ml Lincomycin, 5 mg/ml Amphotericin B
and 25 mg/ml Gentamicin, or one or more thereof.
, .
g~l Pourous Sheet Type Another type of collagen skin dressing (porous sheet) was prepared as follows: Solubilized collagen gel (pH 2.0 -
3.5, collagen concentration 1% - 10%) was extruded from a tubular nozzle into coagulation bath (saturated NaCl).
Coagulated tubular collagen was cut longitudinally to obtain sheet and tanned with 1 - 5~ glutaraldehyde in saturated NaCl containing 0.05 M Na2HPO4 for 0.5 - 3.0 hours. Tanned collagen sheet was washed with water repeatedly, then freeze-dried on methylmethacrylate plate. To produce a semi-porous, film type sheet in which the upper surface of the sheet is more concentrated in collagen (resulting in an upper film type surface) and in which the lower surface of the sheet is less concentrated in collagen (i.e. more porous) the sheet is sub~ect to partial air-drying prior to freeze-drying. Collagen sheet was sterilized by ethylene oxide gas and soaked in a typical base solution containing one or more bactericidal agents, such as silver nitrate (0.5 g/100 ml), or silver lactate (0.5 g/100 ml), or lactated Ringer's solution containing 25 mg/ml Gentamicin, 25 mg/ml Lincomycin, 25 mg/ml Colistimethate, 25 mg/ml Kanamycin, and 5 mg/ml Amphotericin B; or lactated Ringer's solution containing 25 mg/ml Lincomycin, 5 mg/ml Amphotericin B, and 25 mg/ml Gentamicin.
An effective skin dressing should have the following properties:
1. good adherence to wound surface, 2. prevention of loss of protein, fluid and electrolytes, 3. prevention of infection,
Coagulated tubular collagen was cut longitudinally to obtain sheet and tanned with 1 - 5~ glutaraldehyde in saturated NaCl containing 0.05 M Na2HPO4 for 0.5 - 3.0 hours. Tanned collagen sheet was washed with water repeatedly, then freeze-dried on methylmethacrylate plate. To produce a semi-porous, film type sheet in which the upper surface of the sheet is more concentrated in collagen (resulting in an upper film type surface) and in which the lower surface of the sheet is less concentrated in collagen (i.e. more porous) the sheet is sub~ect to partial air-drying prior to freeze-drying. Collagen sheet was sterilized by ethylene oxide gas and soaked in a typical base solution containing one or more bactericidal agents, such as silver nitrate (0.5 g/100 ml), or silver lactate (0.5 g/100 ml), or lactated Ringer's solution containing 25 mg/ml Gentamicin, 25 mg/ml Lincomycin, 25 mg/ml Colistimethate, 25 mg/ml Kanamycin, and 5 mg/ml Amphotericin B; or lactated Ringer's solution containing 25 mg/ml Lincomycin, 5 mg/ml Amphotericin B, and 25 mg/ml Gentamicin.
An effective skin dressing should have the following properties:
1. good adherence to wound surface, 2. prevention of loss of protein, fluid and electrolytes, 3. prevention of infection,
4. reduction of pain,
5. no stimulation of local tissue response, etc.
Collagen skin dressings described here satisfy the above - a _ ' :
g71 properties and are easy to use and less expensive. Gel skin dressing is especially suitable for application to irregular surfaces e.g., joint surfaces. Viscous gel-like paste and gels of petroleum jelly consistency show excellent adherence to wound surfaces. Porous sheet, and semi-porous film type dressings also adhere firmly to the wound. Extensive cell ingrowth into the porous collagen sheet was observed. All skin dressings indicated effective protection against infection and good wound healing.
The present invention may be further understood from the following examples:
-Fresh calfskin (about 5 kg) was dehaired, cleaned by shaving and cut into small pieces. The skin was washed repeatedly with 10% NaCl containing a 0.2~ sodium azide bactericide and with sterilized water. The skin was solubilized in 10 liters of water (pH 2.5 HCl) containing 30 mg/ml Gentamicin by addition of 1 g. of pepsin (approximate ratio of enzyme to colla~en was 1/400) at 20C for 4 days with intermittent stirring. The resulting viscous solubilized collagen was filtered through cheesecloth, its pH raised to 10 by NaOH and allowed to stand for 24 hours at 20C to inactivate the pepsin.
The pH of collagen was then adjusted to 7-8 (HCl) and collagen precipitate was collected by centrifuging and washed with sterilized water. The washed precipitate was redissolved in acidic solution and reprecipitated at pH 7-8 for further purification.
Succinylation of solubilized collagen was preformed as follows: Ten grams (dry basis) of solubilized collagen precipitate was resuspended in 4 liters of water and its pH
adjusted to 9.0 by NaOH. Acetone solution (100 ml) containing 97~
2.0 g of succinic anhydride was gradually added to the collagen suspension. During the addition of succinic anhydride the pH
of collagen suspension was maintained at about 9.0 by NaOH
solution. Succinylated collagen was precipitated by acidification to about pH 4.2, washed with water and freeze-dried. This freeze-dried collagen (sponge-like in form) was sterilized to remove micro-organisms. Five grams of the sterilized collagen sponge was dissolved in acidified water. Upon addition of NaOH
to a pH of abo~t 7.4 the collagen emerges in a highly viscous form. It was preserved by addition of silver nitrate (0.5%
solution). This gel skin dressing was excellent in adhesion to the wound, in wound healing, and in protection against infection.
Succinylated solubilized collagen was prepared by the method described in Example 1. Sterilized succinylated collagen (10 g) was treated in the same manner as in Example 1 but preserved by Silver Lactate (0.5% solution). This gel skin dressing again displayed excellent properties as above.
_ .
Sterilized succinylated collagen was prepared by the method described in Example 1 and treated in the same manner as in Example 1 but was preserved in sterile lactated Ringer's solution (0.6~ NaCl, 0.31% sodium lactate, 0.03% potassium chloride, 0.02% calcium chloride, pH adjusted to 7.4) containing the following antibiotics: 25 mg/ml Lincomycin, 5 mg/ml Ampho-tericin B, and 25 mg/ml Gentamicin. This gel skin dressing once again displayed excellent properties. -, Solubilized collagen (not succinylated) was prepared by the method described in Example 1. The collagen was dissolved in dilute HCL solution (final pH 2.5, collagen concentration .~
was 3~) and deairated under vacuum. Collagen acidic gel was extruded into a coagulation bath (saturated NaCl) through an appropriate nozzle. Coagulated tubing was recovered and cut longitudinally to make it into sheets and tanned with 3%
glutaraldehyde in saturated NaCl containing 0.05 M Na2HPO4 for one hour. After repeated washing with water, collagen sheet was freeze-dried on a plate of methylmethacrylate.
Freeze-dried sheets (10 cm x 10 cm) were sterilized by treatment with ethylene oxide gas and preserved by soaking in 0.5~ silver nitrate solution. Final thickness of the sheet was 3 mm. This skin dressing was excellent in the adhesion to the wound, in protection against fluid 105s and infection, and in wound healing.
Collagen sheet was prepared by extrusion, tanning and washing by the method described in Example 4, except using 5%
acidic collagen gel. Washed collagen sheet was then partially air-dried on a plate of methylmethacrylate until the thickness of the sheet became half of the original. This partial drying reduces the porosity (collagen concentration higher) of the upper surface of the sheet. It was then freeze-dried to render the lower surface porous (collagen concentration lower), and sterilized with ethylene oxide gas. Sterilized sheet was preserved in sterilie 0.5~ silver lactate solution pH 7.4). The final thickness of the sheet was 2 mm. This skin dressing had finer porosity and greater strength than the sheet of Example 4.
It was excellent in protection of protein, fluid and electrolytes loss, in protection against infection and in wound healing.
Sterile, freeze-dried collagen sheet was prepared by the method described in Example 4, except that the collagen concen-~ 71 tration was 5%. The sheet was preserved by soaking in sterile lactated Ringer's solution (pH adjusted to 7.4) containing the following antibiotics: 25 mg/ml Gentamicin, 25 mg/ml Lincomycin, 25 mg/ml Colistimethate, 25 mg/ml Kanamycin and S mg/ml Amphotericin B. The final thickness of the sheet was 4 mm. This sheet likewise displayed excellent skin dressing properties.
Collagen skin dressings described here satisfy the above - a _ ' :
g71 properties and are easy to use and less expensive. Gel skin dressing is especially suitable for application to irregular surfaces e.g., joint surfaces. Viscous gel-like paste and gels of petroleum jelly consistency show excellent adherence to wound surfaces. Porous sheet, and semi-porous film type dressings also adhere firmly to the wound. Extensive cell ingrowth into the porous collagen sheet was observed. All skin dressings indicated effective protection against infection and good wound healing.
The present invention may be further understood from the following examples:
-Fresh calfskin (about 5 kg) was dehaired, cleaned by shaving and cut into small pieces. The skin was washed repeatedly with 10% NaCl containing a 0.2~ sodium azide bactericide and with sterilized water. The skin was solubilized in 10 liters of water (pH 2.5 HCl) containing 30 mg/ml Gentamicin by addition of 1 g. of pepsin (approximate ratio of enzyme to colla~en was 1/400) at 20C for 4 days with intermittent stirring. The resulting viscous solubilized collagen was filtered through cheesecloth, its pH raised to 10 by NaOH and allowed to stand for 24 hours at 20C to inactivate the pepsin.
The pH of collagen was then adjusted to 7-8 (HCl) and collagen precipitate was collected by centrifuging and washed with sterilized water. The washed precipitate was redissolved in acidic solution and reprecipitated at pH 7-8 for further purification.
Succinylation of solubilized collagen was preformed as follows: Ten grams (dry basis) of solubilized collagen precipitate was resuspended in 4 liters of water and its pH
adjusted to 9.0 by NaOH. Acetone solution (100 ml) containing 97~
2.0 g of succinic anhydride was gradually added to the collagen suspension. During the addition of succinic anhydride the pH
of collagen suspension was maintained at about 9.0 by NaOH
solution. Succinylated collagen was precipitated by acidification to about pH 4.2, washed with water and freeze-dried. This freeze-dried collagen (sponge-like in form) was sterilized to remove micro-organisms. Five grams of the sterilized collagen sponge was dissolved in acidified water. Upon addition of NaOH
to a pH of abo~t 7.4 the collagen emerges in a highly viscous form. It was preserved by addition of silver nitrate (0.5%
solution). This gel skin dressing was excellent in adhesion to the wound, in wound healing, and in protection against infection.
Succinylated solubilized collagen was prepared by the method described in Example 1. Sterilized succinylated collagen (10 g) was treated in the same manner as in Example 1 but preserved by Silver Lactate (0.5% solution). This gel skin dressing again displayed excellent properties as above.
_ .
Sterilized succinylated collagen was prepared by the method described in Example 1 and treated in the same manner as in Example 1 but was preserved in sterile lactated Ringer's solution (0.6~ NaCl, 0.31% sodium lactate, 0.03% potassium chloride, 0.02% calcium chloride, pH adjusted to 7.4) containing the following antibiotics: 25 mg/ml Lincomycin, 5 mg/ml Ampho-tericin B, and 25 mg/ml Gentamicin. This gel skin dressing once again displayed excellent properties. -, Solubilized collagen (not succinylated) was prepared by the method described in Example 1. The collagen was dissolved in dilute HCL solution (final pH 2.5, collagen concentration .~
was 3~) and deairated under vacuum. Collagen acidic gel was extruded into a coagulation bath (saturated NaCl) through an appropriate nozzle. Coagulated tubing was recovered and cut longitudinally to make it into sheets and tanned with 3%
glutaraldehyde in saturated NaCl containing 0.05 M Na2HPO4 for one hour. After repeated washing with water, collagen sheet was freeze-dried on a plate of methylmethacrylate.
Freeze-dried sheets (10 cm x 10 cm) were sterilized by treatment with ethylene oxide gas and preserved by soaking in 0.5~ silver nitrate solution. Final thickness of the sheet was 3 mm. This skin dressing was excellent in the adhesion to the wound, in protection against fluid 105s and infection, and in wound healing.
Collagen sheet was prepared by extrusion, tanning and washing by the method described in Example 4, except using 5%
acidic collagen gel. Washed collagen sheet was then partially air-dried on a plate of methylmethacrylate until the thickness of the sheet became half of the original. This partial drying reduces the porosity (collagen concentration higher) of the upper surface of the sheet. It was then freeze-dried to render the lower surface porous (collagen concentration lower), and sterilized with ethylene oxide gas. Sterilized sheet was preserved in sterilie 0.5~ silver lactate solution pH 7.4). The final thickness of the sheet was 2 mm. This skin dressing had finer porosity and greater strength than the sheet of Example 4.
It was excellent in protection of protein, fluid and electrolytes loss, in protection against infection and in wound healing.
Sterile, freeze-dried collagen sheet was prepared by the method described in Example 4, except that the collagen concen-~ 71 tration was 5%. The sheet was preserved by soaking in sterile lactated Ringer's solution (pH adjusted to 7.4) containing the following antibiotics: 25 mg/ml Gentamicin, 25 mg/ml Lincomycin, 25 mg/ml Colistimethate, 25 mg/ml Kanamycin and S mg/ml Amphotericin B. The final thickness of the sheet was 4 mm. This sheet likewise displayed excellent skin dressing properties.
Claims (27)
1. A process for the preparation of porous collagen skin dressing which comprises forming a collagen gel, ex-truding the collagen gel into a coagulation bath, forming a sheet of collagen from the extruded gel, cross-linking the extruded collagen, and subjecting the cross-linked sheet to freeze-drying.
2. The process of claim 1 in which the cross-linking is carried out by tanning with glutaraldehyde.
3. The process of claim 1, which comprises the steps of:
a) treating a source of collagen with a proteolytic enzyme to form a telopeptide-poor, monomolecularly disper-sed atelocollagen extract, b) precipitating atelocollagen from the extract, c) purifying the precipitated atelocollagen by redis-solving and reprecipitation, d) converting the extracted, purified atelocollagen to a gel, e) extruding the atelocollagen gel through a circular extrusion nozzle in a coagulation bath, f) recovering atelocollagen in tubular form from the coagulation bath, g) slitting the tubular collagen longitudinally to form a collagen sheet therefrom, h) cross-linking the longitudinal sheet, and i) subjecting the cross-linked sheet to freeze-drying.
a) treating a source of collagen with a proteolytic enzyme to form a telopeptide-poor, monomolecularly disper-sed atelocollagen extract, b) precipitating atelocollagen from the extract, c) purifying the precipitated atelocollagen by redis-solving and reprecipitation, d) converting the extracted, purified atelocollagen to a gel, e) extruding the atelocollagen gel through a circular extrusion nozzle in a coagulation bath, f) recovering atelocollagen in tubular form from the coagulation bath, g) slitting the tubular collagen longitudinally to form a collagen sheet therefrom, h) cross-linking the longitudinal sheet, and i) subjecting the cross-linked sheet to freeze-drying.
4. The process of claim 3 in which the cross-linking is carried out by tanning with glutaraldehyde.
5. The process of claim 1 wherein there is included at least one material selected from antibiotics and bacte-ricidal agents.
6. The process of claim 2 wherein there is included at least one material selected from antibiotics and bacte-ricidal agents.
7. The process of claim 3 wherein there is included at least one material selected from antibiotics and bacte-ricidal agents.
8. The process of claim 4 wherein there is included at least one material selected from antibiotics and bacte-ricidal agents.
9. A process for the preparation of collagen skin dressing of limited porosity which comprises forming a collagen gel, extruding the collagen gel into a coagulation bath, forming a sheet of collagen from the extruded gel, cross-linking the extruded collagen, partially air-drying the cross-linked sheet, and subjecting the partially air-dried sheet to freeze-drying.
10. The process of claim 9 in which the cross-linking is carried out by tanning with glutaraldehyde.
11. The process of claim 9 for the preparation of a collagen skin dressing in sheet form whose upper and lower surfaces possess differing porosity characteristics which comprises the steps of:
a) treating a source of collagen with a proteolytic enzyme to form a telopeptide-poor, monomolecularly disper-sed atelocollagen extract, b) precipitating atelocollagen from the extract, c) purifying the precipitated atelocollagen by redis-solving and reprecipitation, d) converting the extracted, purified atelocollagen to a gel, e) extruding the atelocollagen gel through a circular extrusion nozzle in a coagulation bath, f) recovering atelocollagen in tubular form from the coagulation bath, g) slitting the tubular collagen longitudinally to form a collagen sheet therefrom, h) cross-linking the longitudinal sheet, i) partially air-drying the cross-linked sheet, and j) freeze-drying the partially air-dried sheet where-by the upper surface of said sheet becomes more concentra-ted in ateloeollagen content than the lower surface thereof.
a) treating a source of collagen with a proteolytic enzyme to form a telopeptide-poor, monomolecularly disper-sed atelocollagen extract, b) precipitating atelocollagen from the extract, c) purifying the precipitated atelocollagen by redis-solving and reprecipitation, d) converting the extracted, purified atelocollagen to a gel, e) extruding the atelocollagen gel through a circular extrusion nozzle in a coagulation bath, f) recovering atelocollagen in tubular form from the coagulation bath, g) slitting the tubular collagen longitudinally to form a collagen sheet therefrom, h) cross-linking the longitudinal sheet, i) partially air-drying the cross-linked sheet, and j) freeze-drying the partially air-dried sheet where-by the upper surface of said sheet becomes more concentra-ted in ateloeollagen content than the lower surface thereof.
12. The process of claim 11 in which the cross-link-ing is carried out by tanning with glutaraldehyde.
13. The process of claim 9 wherein there is included at least one material selected from antibiotics and bacte-ricidal agents.
14. The process of claim 10 wherein there is included at least one material selected from antibiotics and bacte-ricidal agents.
15. The process of claim 11 wherein there is included at least one material selected from antibiotics and bacte-ricidal agents.
16. The process of claim 12 wherein there is included at least one material selected from antibiotics and bacte-ricidal agents.
17. A skin dressing of petroleum jelly consistency comprising enzyme-solubilized acylated atelocollagen gel and at least one substance selected from antibiotics and bacte-ricides.
18. A skin dressing according to claim 17 in which the acylated atelocollagen is succinylated atelocollagen.
19. A skin dressing of petroleum jelly consistency comprising solubilized succinylated collagen gel and at least one material selected from bactericidal agents and antibiotics.
20. A method for the preparation of a collagen skin dressing in gel form which comprises the steps of:
a) treating a source of collagen with a proteolytic enzyme to form a telopeptide-poor, monomolecularly disper-sed atelocollagen extract, b) precipitating atelocollagen from the extract, c) reacting an aqueous dispersion of the atelocollagen extract with an acylating agent, d) separating acylated atelocollagen from the reaction mixture, and e) converting the acylated atelocollagen to a gel of petroleum jelly consistency.
a) treating a source of collagen with a proteolytic enzyme to form a telopeptide-poor, monomolecularly disper-sed atelocollagen extract, b) precipitating atelocollagen from the extract, c) reacting an aqueous dispersion of the atelocollagen extract with an acylating agent, d) separating acylated atelocollagen from the reaction mixture, and e) converting the acylated atelocollagen to a gel of petroleum jelly consistency.
21. The method according to claim 20 in which the acylating agent is succinic anhydride.
22. The method according to claim 20 in which the acylated atelocollagen is purified by solution and re-pre-cipitation prior to its conversion to a gel.
23. The method according to claim 21 in which the acylated atelocollagen is purified by solution and re-pre-cipitation prior to its conversion to a gel.
24. The method according to claim 20 in which there is incorporated into the gel at least one substance selected from antibiotics and bactericides.
25. The method according to claim 21 in which there is incorporated into the gel at least one substance selected from antibiotics and bactericides.
26. The method according to claim 22 in which there is incorporated into the gel at least one substance selected from antibiotics and bactericides.
27. The method according to claim 23 in which there is incorporated into the gel at least one substance selected from antibiotics and bactericides.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US80500377A | 1977-06-09 | 1977-06-09 | |
US805,003 | 1977-06-09 |
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CA1110971A true CA1110971A (en) | 1981-10-20 |
Family
ID=25190460
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA304,330A Expired CA1110971A (en) | 1977-06-09 | 1978-05-29 | Collagen skin dressing |
Country Status (22)
Country | Link |
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JP (1) | JPS545019A (en) |
AR (1) | AR215499A1 (en) |
AT (1) | AT361129B (en) |
AU (1) | AU519348B2 (en) |
BE (1) | BE867988A (en) |
BR (1) | BR7803698A (en) |
CA (1) | CA1110971A (en) |
CH (1) | CH641963A5 (en) |
DE (1) | DE2823620A1 (en) |
DK (1) | DK152665B (en) |
ES (1) | ES470645A1 (en) |
FI (1) | FI781816A (en) |
FR (1) | FR2393581A1 (en) |
GB (2) | GB1602339A (en) |
HK (2) | HK43483A (en) |
IT (1) | IT1098321B (en) |
MY (2) | MY8400232A (en) |
NL (1) | NL7806067A (en) |
NO (1) | NO150585C (en) |
PH (1) | PH17316A (en) |
SE (1) | SE7806677L (en) |
SG (1) | SG27983G (en) |
Families Citing this family (11)
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JPS564651B2 (en) * | 1974-06-19 | 1981-01-31 | ||
DE2943520C2 (en) * | 1979-10-27 | 1982-05-19 | Fa. Carl Freudenberg, 6940 Weinheim | Process for the production of collagen sponge for medical or cosmetic purposes |
CA1190855A (en) * | 1980-09-03 | 1985-07-23 | Rolf W. Pfirrmann | Treatment of osteitis |
DE3037513C2 (en) * | 1980-10-03 | 1983-05-05 | Steffan, Wolfgang, 8425 Neustadt | Collagen wound dressing |
SE446688C (en) * | 1982-09-14 | 1989-10-16 | Magnus Hoeoek | Means for the removal of microorganisms from tissues, which consist of a protein that can be bound to the microorganisms |
AU569112B2 (en) * | 1983-02-08 | 1988-01-21 | Nitta Gelatin Co. Ltd. | Crosslinked collagen products |
JPS61168363A (en) * | 1985-01-22 | 1986-07-30 | 株式会社 高研 | Succinated aterocollagen solution for viscosegery or substitute glass body |
US4911710A (en) * | 1985-11-13 | 1990-03-27 | Domedica Pty. Limited | Treatment of collagenous tissue |
DE19856668A1 (en) * | 1998-12-09 | 2000-06-15 | Aesculap Ag & Co Kg | Active substance matrix in the form of a bioabsorbable porous nonwoven, process for its preparation and use |
GB2444323B (en) * | 2006-11-30 | 2011-04-06 | Ethicon Inc | Protein sheet material |
US10213526B2 (en) * | 2014-03-21 | 2019-02-26 | University Of Pittsburgh-Of The Commonwealth System Of Higher Education | Methods for preparation of a terminally sterilized hydrogel derived from extracellular matrix |
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FR1486237A (en) * | 1967-10-04 | |||
GB942226A (en) * | 1960-10-25 | 1963-11-20 | Ethicon Inc | Article and the preparation thereof |
AT252456B (en) * | 1963-12-16 | 1967-02-27 | Ethicon Inc | Process for making collagen products |
US3368911A (en) * | 1965-03-25 | 1968-02-13 | Ethicon Inc | Collagen-carbonic acid surgical sponge |
FR6652M (en) * | 1966-12-28 | 1969-01-27 | ||
DE1811290C3 (en) * | 1968-11-27 | 1980-02-14 | Milos Dr.Med Dr.Se. 8000 Muenchen Chvapil | Process for the production of collagen fiber braids in the form of felt-like membranes or sponge-like layers |
FR1596790A (en) * | 1968-11-27 | 1970-06-22 | ||
US3632361A (en) * | 1969-06-26 | 1972-01-04 | Fmc Corp | Water-insoluble microcrystalline collagen absorbent mat |
FR2170893A1 (en) * | 1972-02-07 | 1973-09-21 | Flacara R Intreprinderea | Therapeutic bandages prepn - from collagen dispersions by quick-freezing and vacuum - sublimation |
DE2348685C2 (en) * | 1973-09-27 | 1984-07-26 | Nippi Inc., Tokyo | Process for the production of a non-woven fabric based on collagen |
US3939831A (en) * | 1974-03-04 | 1976-02-24 | Intreprinderea Flacara Rosie | Process for preparing medicinal dressings |
CH627078A5 (en) * | 1975-06-05 | 1981-12-31 | Pentapharm Ag | Process for the preparation of a sterile collagen product with felt-like or web-like fibre structure |
JPS5365358A (en) * | 1976-11-22 | 1978-06-10 | Nippi Inc | Collagen fiber dispersion |
-
1978
- 1978-05-15 GB GB19620/78A patent/GB1602339A/en not_active Expired
- 1978-05-15 GB GB22246/80A patent/GB1602340A/en not_active Expired
- 1978-05-23 FR FR787815293A patent/FR2393581A1/en active Granted
- 1978-05-29 CA CA304,330A patent/CA1110971A/en not_active Expired
- 1978-05-30 DE DE2823620A patent/DE2823620A1/en active Granted
- 1978-05-30 PH PH21210A patent/PH17316A/en unknown
- 1978-06-05 NL NL7806067A patent/NL7806067A/en not_active Application Discontinuation
- 1978-06-07 IT IT24302/78A patent/IT1098321B/en active
- 1978-06-07 FI FI781816A patent/FI781816A/en not_active Application Discontinuation
- 1978-06-08 JP JP6928678A patent/JPS545019A/en active Granted
- 1978-06-08 BR BR7803698A patent/BR7803698A/en unknown
- 1978-06-08 NO NO782005A patent/NO150585C/en unknown
- 1978-06-08 DK DK256278AA patent/DK152665B/en not_active Application Discontinuation
- 1978-06-08 ES ES470645A patent/ES470645A1/en not_active Expired
- 1978-06-08 SE SE7806677A patent/SE7806677L/en unknown
- 1978-06-09 AT AT418778A patent/AT361129B/en not_active IP Right Cessation
- 1978-06-09 AR AR272526A patent/AR215499A1/en active
- 1978-06-09 BE BE188463A patent/BE867988A/en not_active IP Right Cessation
- 1978-06-09 CH CH630278A patent/CH641963A5/en not_active IP Right Cessation
- 1978-06-16 AU AU37184/78A patent/AU519348B2/en not_active Expired
-
1983
- 1983-05-20 SG SG279/83A patent/SG27983G/en unknown
- 1983-10-20 HK HK434/83A patent/HK43483A/en unknown
- 1983-10-20 HK HK435/00A patent/HK43583A/en unknown
-
1984
- 1984-12-30 MY MY232/84A patent/MY8400232A/en unknown
- 1984-12-30 MY MY233/84A patent/MY8400233A/en unknown
Also Published As
Publication number | Publication date |
---|---|
AR215499A1 (en) | 1979-10-15 |
MY8400233A (en) | 1984-12-31 |
JPS6330023B2 (en) | 1988-06-16 |
HK43583A (en) | 1983-10-28 |
BE867988A (en) | 1978-10-02 |
CH641963A5 (en) | 1984-03-30 |
FR2393581B1 (en) | 1984-05-25 |
NO150585B (en) | 1984-08-06 |
IT7824302A0 (en) | 1978-06-07 |
IT1098321B (en) | 1985-09-07 |
GB1602340A (en) | 1981-11-11 |
BR7803698A (en) | 1979-03-20 |
JPS545019A (en) | 1979-01-16 |
AT361129B (en) | 1981-02-25 |
AU519348B2 (en) | 1981-11-26 |
HK43483A (en) | 1983-10-28 |
DE2823620A1 (en) | 1979-01-11 |
NL7806067A (en) | 1978-12-12 |
NO782005L (en) | 1978-12-12 |
NO150585C (en) | 1984-11-14 |
GB1602339A (en) | 1981-11-11 |
FR2393581A1 (en) | 1979-01-05 |
SG27983G (en) | 1984-04-19 |
DK152665B (en) | 1988-04-11 |
MY8400232A (en) | 1984-12-31 |
FI781816A (en) | 1978-12-10 |
ES470645A1 (en) | 1979-09-01 |
DK256278A (en) | 1978-12-10 |
SE7806677L (en) | 1978-12-10 |
AU3718478A (en) | 1979-12-20 |
PH17316A (en) | 1984-07-20 |
DE2823620C2 (en) | 1987-03-12 |
ATA418778A (en) | 1980-07-15 |
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