WO1990003810A1 - Delayed release compositions for wound healing - Google Patents
Delayed release compositions for wound healing Download PDFInfo
- Publication number
- WO1990003810A1 WO1990003810A1 PCT/GB1989/001184 GB8901184W WO9003810A1 WO 1990003810 A1 WO1990003810 A1 WO 1990003810A1 GB 8901184 W GB8901184 W GB 8901184W WO 9003810 A1 WO9003810 A1 WO 9003810A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- growth factor
- compositions
- wound healing
- hydrogel
- delayed release
- Prior art date
Links
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- 230000029663 wound healing Effects 0.000 title claims abstract description 6
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
- A61L26/0052—Mixtures of macromolecular compounds
-
- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0066—Medicaments; Biocides
-
- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/008—Hydrogels or hydrocolloids
-
- 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
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
-
- 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
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/602—Type of release, e.g. controlled, sustained, slow
Definitions
- This invention relates to wound healing and in particular to novel delayed release compositions for use in wound healing.
- the growth factors here concerned include
- Cys Asn Cys Val lie Gly Tyr Ser Gly Asp
- the above growth factors may be in the natural form or may be made by recombinant DNA technology.
- sequences may be added at the N- and C-terminal
- aqueous hydrogels which carry the growth factors are the hydrogels of USP 4,556,056, a commercial embodiment of which is sold under the name Geliperm, and related materials.
- the hydrogels will normally comprise at least on gellable protein, polypeptide or polysaccharide interspersed with at least one hydrophilic polymer and be swollen with an aqueous solution containing one or more of the said growth factors, optionally together with nutrients and or other growth factors.
- the hydrophilic polymer in the hydrogel may for example be a polymer of a hydrophilic acrylic or methacrylic acid derivative or vinylpyrrolidine.
- the acrylic or methacrylic acid derivative is preferably an amide, as in polyacrylamide which is the preferred polymer, or an ester with an alkanol or polyol.
- the chains of the polymer will normally be interspersed with the chains of the gellable substance preferably by polymerisation in the presence of a solution of the latter.
- a crosslinking agent such as N,N 1 -methylene-bis- acrylamide may be present.
- the gellable substance is preferably a poly- saccharide, agar-agar being particularly preferred;
- gelatin is preferred.
- solid matrix of the gel may constitute only 2 to
- the hydrogel will generally take the form
- the dressings may advantageously be perforated.
- the aqueous medium within the gel may usefully contain the essential amino acids and trace minerals normally provided for wound alimentation.
- Hydrogel dressings according to the invention may be used in surgery in the preparation of the wound base for free skin transplantation; in the treatment of the donor site after the removal of split skin grafts in plastic surgery and for covering superficial operation wounds to prevent exposed bradytrophic tissue (tendons, periostium, bone
- hydrogel dressings may be used in the treatment of both fresh and chronic damage to the epithelium
- the mixture has a temperature between 50°C
- the gel is partially dehydrated as described in USP 4 556 056, Example 6 and immersed in a
- sheet is sterilised by gamma radiation.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Materials Engineering (AREA)
- Inorganic Chemistry (AREA)
- Endocrinology (AREA)
- Molecular Biology (AREA)
- Diabetes (AREA)
- Dermatology (AREA)
- Dispersion Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides delayed release compositions for use in wound healing comprising a hydrogel containing one or more gellable proteins, peptides or polysaccharides interspersed with a hydrophilic polymer said hydrogel being swollen with an aqueous solution containing one or more growth factors selected from epidermal growth factor, human fibroblast growth factor, human insulin-like growth factor and platelet derived growth factor.
Description
DELAYED RELEASE COMPOSITIONS FOR WOUND HEALING
This invention relates to wound healing and in particular to novel delayed release compositions for use in wound healing.
A number of growth factors have been found with are able to stimulate growth of new tissues when applied to open wounds. There are problems, however, in applying such factors in the optimal way to ensure continued growth while maintaining the sterility of the wound. We have now found that certain hydrogels more particularly defined below are surprisingly more suitable than other compositions investigated for the application and sustained release of a number of polypeptide growth factors.
The growth factors here concerned include
Epidermal Growth Factor, Fibroblast Growth Factor,
Insulin-like Growth Factor and Platelet Derived
Growth Factor.
In particular, the following Growth Factors ape particularly well released by the hydrogels here concerned:
Epidermal Growth Factor - Compound 1
Asn Ser Tyr Pro Gly Cys Pro Ser Ser Tyr
Asp Gly Tyr Cys Leu Asn Gly Gly Val Cys
Met His lle Glu Ser Leu Asp Ser Tyr Thr
Cys Asn Cys Val lie Gly Tyr Ser Gly Asp
Arg Cys Gin Thr Arg Asp Leu Arg Trp Trp
Glu Leu Arg.
Human Fibroblast Growth Factor - Compound 2
ProAlaLeuProGluAspGlyGlySerGlyAlaPheProProGlyHisPheLysAsp
ProLysArgLeuTyrCysLysAsnGlyGlyPhePheLeuArglleHisProAspGlyArg
ValAspGlyValArgGluLysSerAspProHisIleLysLeuGlnLeuGlnAlaGluGlu
ArgGlyValValSerlleLysGlyValCysAlaAsnArgTyrLeuAlaMetLysGluAsp
GlyArgLeuLeuAlaSerLysCysValThrAspGluCysPhePhePheGluArgLeuGlu
SerAsnAsnTyrAsnThrTyrArgSerArgLysTyrThrSerTrpTyrValAlaLeuLys
ArgThrGlyGlnTyrLysLeuGlySerLysThrGlyProGlyGlnLysAlalleLeuPhe
LeuProMetSerAlaLysSer
Human Insulin-like Growth Factor - Compound 3
Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu
Val Asp Ala Leu Gln Phe Val Cys Gly Asp
Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly
Tyr Gly Ser Ser Ser Arg Arg Ala Pro Gln
Thr Gly lle Val Asp Glu Cys Cys Phe Arg
Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr
Cys Ala Pro Leu Lys Pro Ala Lys Ser Ala
Platelet Derived Growth Factor Compound 4
20 40 60
A-chain MRTLACLLLLCCCYLAHVLAEEAEIPREVIERLARSQLHSIADLORLLEIDSVGSEDS LDTSL B-chain MNRCWPLFLSLCOYLRLVSAEGDPIPEELYEMLSDHSIPSFDDLQRLLHGDPGEEDGAELDLNM
80 100 120
A-chain RAHGVHATKHVPGKRPLPIRRKRSIEEAVPAVCKTRTVIYEIPRSOVDPTSANFLIWPPCVEVKR B-chain TRSHSGGELESLARGRRSLGSLTIAEPAMIAECKTRTEVFEISRRLIDRTNANFLVWPPCVEVQR
140 160 180
A-chain CTGCCNTSSVKO0PSRVHHRSVXVAKVEYVAKKPKLKEV0VPLEEHLECACATTSLNPDYREEDT B-chain CSGCCNNRNVOORPTQVOLRPVQVrRKIEIVRKKPIFKKATVTLEDHLACKCETVAAARPVTRSPG
210
A-chain GRPRESCKKAKAKALKPT
B-chain GSOEORAKTPOTRVTIRTVAVRRPPKGKHRKFKHTHDKTALKETLGA
It will be appreciated that analogues of the above growth factors, for example from different annual species which differ from the above sequences by
a few amino acids, will be expected to behave in
the same way in the gel formulations of the invention.
The above growth factors may be in the natural form or may be made by recombinant DNA technology.
In the latter case up to 20%, e.g. 10 amino acid
units, may be varied provided the growth factor
activity is retained. Additional amino acids or
sequences may be added at the N- and C-terminal
ends, e.g. signal sequences or methionine at the
N-terminal or amino acids corresponding to stop
codons. Salts of the polypeptides are also included.
The above growth factors can be obtained
from Amgen Inc. of Thousand Oakes, California.
The aqueous hydrogels which carry the growth factors are the hydrogels of USP 4,556,056, a commercial embodiment of which is sold under the name Geliperm, and related materials.
The hydrogels will normally comprise at least on gellable protein, polypeptide or polysaccharide interspersed with at least one hydrophilic polymer and be swollen with an aqueous solution containing one or more of the said growth factors, optionally together with nutrients and or other growth factors.
The hydrophilic polymer in the hydrogel may for example be a polymer of a hydrophilic acrylic or methacrylic acid derivative or vinylpyrrolidine.
The acrylic or methacrylic acid derivative is preferably an amide, as in polyacrylamide which is the preferred polymer, or an ester with an alkanol or polyol.
The chains of the polymer will normally be interspersed with the chains of the gellable substance preferably by polymerisation in the presence of a solution
of the latter. Apart from a polymerisation initiator, a crosslinking agent such as N,N1-methylene-bis- acrylamide may be present.
The gellable substance is preferably a poly- saccharide, agar-agar being particularly preferred;
of the gellable proteins, gelatin is preferred.
The water content of such a hydrogel can
be very high, for example in the range of 95 to
98% by weight, preferably about 97%. Thus, the
solid matrix of the gel may constitute only 2 to
5% by weight of the gel, preferably about 3%.
In general, the most preferred hydrogels
comprise (a) agar-agar together with (b) polyacrylamide cross-linked with about 2% by weight of N,N -methylene bis-acrylamide, advantageously in the ratio range
1:3 to 1:4, preferably about 1:3.5. This gel,
when fully swollen with water, contains about 96.5% by weight of water. A gel of this type is now
commercially available from Geistlich Pharma of
Wolhusen, Switzerland, under the Registered Trade
Mark Geliperm.
The hydrogel will generally take the form
of a sheet for use as a dressing for direct application to the wound. Such dressings have the advantage of very good compatibility and ease of removable without damage to the growing tissue. In order to accommodate exudation from the wound, the dressings may advantageously be perforated.
The aqueous medium within the gel may usefully contain the essential amino acids and trace minerals normally provided for wound alimentation.
Hydrogel dressings according to the invention may be used in surgery in the preparation of the wound base for free skin transplantation; in the treatment of the donor site after the removal of split skin grafts in plastic surgery and for covering superficial operation wounds to prevent exposed
bradytrophic tissue (tendons, periostium, bone
or cartilate) from drying out. In dermatology,
the hydrogel dressings may be used in the treatment of both fresh and chronic damage to the epithelium
e.g. after dermal abrasion to encourage granulation and the formation of cellular tissue in chronic
ulcers, especially crural ulcers, decubitus sores
etc; in the treatment of patients with polyvalent
allergies when other forms of dressing and external applications are contra-indicated; and in the treatment of superficial thrombo-phlebitis in combination
with external therapeutic measures used in such
cases.
The following Example is given by way of
illustration only:
Example 1
20 g of agar-agar are suspended under agitation in 880 g of deionized water and heated to 95°C
until complete dissolution. 1 litre of a second
aqueous solution containing 70 g of acrylamide
and 1.84 g of N,N'-methylene-bis-acrylamide is
prepared at ambient temperature and added to the
first solution with thorough mixing. Under continued agitation, 2.2 g of N,N,N',N'-tetrakis-(2-hydroxypropyl)- ethylene diamine dissolved in 60 g of water and
then 1.26 g of ammonium peroxidisulfate dissolved
in 40 g of water are added.
The mixture is poured into flat moulds (26
x 12mm) to a depth of 3mm.
The mixture has a temperature between 50°C
and 55°C and begins to polymerize immediately.
After 10 minutes the gel point is reached. The
batch is allowed to cool down overnight during
which time polymerization is completed.
The gel is freed from soluble impurities
by washing with pure flowing water for 24 hours.
With this washing the gel swells to 135% of its
original weight. Such sheet material is now commercially available under the name Geliperm from Geistlich
Pharma of Wolhusen, Switzerland.
The gel is partially dehydrated as described in USP 4 556 056, Example 6 and immersed in a
5% solution of Epidermal Growth Factor (Compound 1) (Amgen Inc, Thousand Oakes, California) until fully swollen. After packaging in polyethylene, the
sheet is sterilised by gamma radiation.
Claims
1. Delayed release compositions for use in wound
healing comprising a hydrogel containing, one or more gellable proteins, peptides or polysaccharides interspersed with a hydrophilic polymer said hydrogel being swollen with an aqueous solution containing one or more growth factors selected from epidermal growth factor, human fibroblast growth factor, human insulin-like growth factor and platelet derived growth factor.
2. Compositions as claimed in claim 1 in which
the gellable component is agar-agar.
3. Compositions as claimed in claim 1 or claim
2 in which the hydrophilic polymer is polyacrylamide.
4. Compositions as claimed in claim 1 containing
95 to 98% by weight of water.
5. Compositions as claimed in claim 1 in the form of sheets for use as wound dressings.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8823649.2 | 1988-10-07 | ||
| GB8823649A GB8823649D0 (en) | 1988-10-07 | 1988-10-07 | Chemical compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1990003810A1 true WO1990003810A1 (en) | 1990-04-19 |
Family
ID=10644908
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB1989/001184 WO1990003810A1 (en) | 1988-10-07 | 1989-10-06 | Delayed release compositions for wound healing |
Country Status (3)
| Country | Link |
|---|---|
| CA (1) | CA2000337A1 (en) |
| GB (1) | GB8823649D0 (en) |
| WO (1) | WO1990003810A1 (en) |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993005823A1 (en) * | 1990-01-12 | 1993-04-01 | Baylink David J | Bone-growth-stimulating composition |
| WO1993019769A1 (en) * | 1992-03-28 | 1993-10-14 | The Victoria University Of Manchester | Wound healing and treatment of fibrotic disorders |
| EP0650366A4 (en) * | 1991-08-30 | 1994-12-20 | Life Medical Sciences Inc | Compositions and methods for treating wounds. |
| US5591709A (en) * | 1991-08-30 | 1997-01-07 | Life Medical Sciences, Inc. | Compositions and methods for treating wounds |
| US5662904A (en) * | 1991-03-28 | 1997-09-02 | The Victoria University Of Manchester | Anti-scarring compositions comprising growth factor neutralizing antibodies |
| WO1999025395A2 (en) * | 1997-11-14 | 1999-05-27 | Acrymed | Improved wound dressing device |
| DE102005035879A1 (en) * | 2005-07-30 | 2007-02-01 | Paul Hartmann Ag | Hydrogel useful as a wound filler or dressing comprises a gel-forming polysaccharide, an acrylic acid derivative and an electrolyte mixture |
| US8900624B2 (en) | 2004-07-30 | 2014-12-02 | Kimberly-Clark Worldwide, Inc. | Antimicrobial silver compositions |
| US9289378B2 (en) | 2004-09-20 | 2016-03-22 | Avent, Inc. | Antimicrobial amorphous compositions |
| US9687503B2 (en) | 1999-12-30 | 2017-06-27 | Avent, Inc. | Devices for delivering oxygen to the wounds |
| US10251392B2 (en) | 2004-07-30 | 2019-04-09 | Avent, Inc. | Antimicrobial devices and compositions |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2146335A (en) * | 1983-09-07 | 1985-04-17 | Ej Ass Inc | Wound healing compositions |
| EP0137743A2 (en) * | 1983-09-13 | 1985-04-17 | Ed. Geistlich Söhne Ag Für Chemische Industrie | Topically administrable pharmaceutical compositions |
| EP0267015A2 (en) * | 1986-11-05 | 1988-05-11 | Ethicon, Inc. | Stabilized compositions containing epidermal growth factor |
| DE3744289A1 (en) * | 1986-12-30 | 1988-07-14 | Politechnika Lodzka | METHOD FOR DISPLAYING HYDROGEL COVERINGS |
| EP0312208A1 (en) * | 1987-09-18 | 1989-04-19 | Ethicon, Inc. | Gel formulations containing growth factors |
| EP0272149B1 (en) * | 1986-12-19 | 1992-03-11 | Coloplast A/S | Medical dresssings |
-
1988
- 1988-10-07 GB GB8823649A patent/GB8823649D0/en active Pending
-
1989
- 1989-10-06 WO PCT/GB1989/001184 patent/WO1990003810A1/en unknown
- 1989-10-10 CA CA 2000337 patent/CA2000337A1/en not_active Abandoned
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2146335A (en) * | 1983-09-07 | 1985-04-17 | Ej Ass Inc | Wound healing compositions |
| EP0137743A2 (en) * | 1983-09-13 | 1985-04-17 | Ed. Geistlich Söhne Ag Für Chemische Industrie | Topically administrable pharmaceutical compositions |
| EP0267015A2 (en) * | 1986-11-05 | 1988-05-11 | Ethicon, Inc. | Stabilized compositions containing epidermal growth factor |
| EP0272149B1 (en) * | 1986-12-19 | 1992-03-11 | Coloplast A/S | Medical dresssings |
| DE3744289A1 (en) * | 1986-12-30 | 1988-07-14 | Politechnika Lodzka | METHOD FOR DISPLAYING HYDROGEL COVERINGS |
| EP0312208A1 (en) * | 1987-09-18 | 1989-04-19 | Ethicon, Inc. | Gel formulations containing growth factors |
Cited By (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993005823A1 (en) * | 1990-01-12 | 1993-04-01 | Baylink David J | Bone-growth-stimulating composition |
| US5461030A (en) * | 1991-02-01 | 1995-10-24 | Life Medical Science, Inc. | Compositions and methods for enhancing wound healing |
| US5662904A (en) * | 1991-03-28 | 1997-09-02 | The Victoria University Of Manchester | Anti-scarring compositions comprising growth factor neutralizing antibodies |
| EP0650366A4 (en) * | 1991-08-30 | 1994-12-20 | Life Medical Sciences Inc | Compositions and methods for treating wounds. |
| EP0650366A1 (en) * | 1991-08-30 | 1995-05-03 | Life Medical Sciences, Inc. | Compositions and methods for treating wounds |
| US5591709A (en) * | 1991-08-30 | 1997-01-07 | Life Medical Sciences, Inc. | Compositions and methods for treating wounds |
| US6331298B1 (en) | 1992-03-28 | 2001-12-18 | Renovo Limited | Wound healing and treatment of fibrotic disorders |
| WO1993019769A1 (en) * | 1992-03-28 | 1993-10-14 | The Victoria University Of Manchester | Wound healing and treatment of fibrotic disorders |
| AU673161B2 (en) * | 1992-03-28 | 1996-10-31 | Renovo Limited | Wound healing and treatment of fibrotic disorders |
| WO1999025395A2 (en) * | 1997-11-14 | 1999-05-27 | Acrymed | Improved wound dressing device |
| WO1999025395A3 (en) * | 1997-11-14 | 1999-08-12 | Acrymed | Improved wound dressing device |
| US6355858B1 (en) | 1997-11-14 | 2002-03-12 | Acrymed, Inc. | Wound dressing device |
| US9687503B2 (en) | 1999-12-30 | 2017-06-27 | Avent, Inc. | Devices for delivering oxygen to the wounds |
| US8900624B2 (en) | 2004-07-30 | 2014-12-02 | Kimberly-Clark Worldwide, Inc. | Antimicrobial silver compositions |
| US9888691B2 (en) | 2004-07-30 | 2018-02-13 | Avent, Inc. | Antimicrobial silver compositions |
| US10251392B2 (en) | 2004-07-30 | 2019-04-09 | Avent, Inc. | Antimicrobial devices and compositions |
| US9289378B2 (en) | 2004-09-20 | 2016-03-22 | Avent, Inc. | Antimicrobial amorphous compositions |
| DE102005035879A1 (en) * | 2005-07-30 | 2007-02-01 | Paul Hartmann Ag | Hydrogel useful as a wound filler or dressing comprises a gel-forming polysaccharide, an acrylic acid derivative and an electrolyte mixture |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2000337A1 (en) | 1990-04-07 |
| GB8823649D0 (en) | 1988-11-16 |
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