US4745098A
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US
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Compositions and method for improving wound healing
Assignee: University of California, San Diego
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Filing: 1984-02-24
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Granted: 1988-05-17
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Expires: 2004-02-24
Abstract
Abstract The healing of wounds is promoted by contacting the wound surfaces with a suspension of collagen and a glycosaminoglycan that is chemotactic for fibroblasts and/or endothelial cells. Typical glycosaminoglycans that exhibit the desired chemotaxis are heparin, heparan sulfate, and alginate. Two or more glycosaminoglycans can be present in the suspensions. Collagen is present in the suspension in the order of 7-10 mg/ml; while the glycosaminoglycan is present in much lower concentrations, e.g., 250-350 mu g/ml. Application of the collagen/glycosaminoglycan suspension to open wounds greatly increases the rate of healing.
Inventors
- 👤 Dov Michaeli
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 07:40
CPC Classifications
A; A61; A61K; A61K38/00; A61K38/16; A61K38/17; A61K38/39; A61P; A61P17/00
Claims Analysis
Total Claims: 61
Claim 1
Independent Claim
75 words
A method for promoting the healing of a surface wound, which method comprises: applying to the wound surface, a liquid aqueous suspension of collagen fibrils in admixture with a minor amount of a glycosaminoglycan wherein said glycosaminoglycan is chemotactic for fibroblasts or endothelial cells and the collagen is not covalently crosslinked to the glycosaminoglycan, wherein said liquid aqueous suspension is applied repeatedly to the wound surface during the healing to effectively promote the healing process.
Claim 2
Independent Claim
75 words
A method for promoting the healing of a surface wound, which method comprises: applying to the wound surface, a liquid aqueous suspension of collagen fibrils in admixture with a minor amount of a glycosaminoglycan wherein said glycosaminoglycan is chemotactic for fibroblasts or endothelial cells and the collagen is not covalently crosslinked to the glycosaminoglycan, wherein said liquid aqueous suspension is applied repeatedly to the wound surface during the healing to effectively promote the healing process.
Claim 3
Dependent Claim
15 words
The method of claim 1 wherein two or more glycosaminoglycans are combined in the suspension.
Claim 4
Dependent Claim
13 words
The method of claim 2 wherein the combined glycosaminoglycans are heparin and alginate.
Claim 5
Dependent Claim
10 words
The method of claim 1 wherein the glycosaminoglycan is heparin.
Claim 6
Dependent Claim
11 words
The method of claim 1 wherein the glycosaminoglycan is heparan sulfate.
Claim 7
Dependent Claim
11 words
The method of claim 1 wherein the glycosaminoglycan is an alginate.
Claim 8
Dependent Claim
12 words
The method of claim 1 wherein the suspension is a saline suspension.
Claim 9
Dependent Claim
10 words
The method of claim 1 wherein the suspension is gelled.
Claim 10
Dependent Claim
26 words
The method of claim 1 wherein the collagen is present in the suspension in concentrations in the order of about 7 to 10 milligrams per milliliter.
Claim 11
Dependent Claim
14 words
The method of claim 1 wherein the glycosaminoglycan is present in chemotactically effective amounts.
Claim 12
Dependent Claim
26 words
The method of claim 10 wherein the glycosaminoglycan is present in the suspension in concentrations in the order of about 100 to 1000 micrograms per milliliter.
Claim 13
Dependent Claim
22 words
The method of claim 1 wherein the glycosaminoglycan is present in the suspension in a concentration of about 250-350 micrograms per milliliter.
Claim 14
Dependent Claim
19 words
The method of claim 1 wherein the ratio of concentration of collagen to glycosaminoglycan is about 25-35 to 1.
Claim 15
Independent Claim
81 words
A method for promoting the healing of a surface wound, which method comprises, applying to the wound surface a suspension of fibrils, itself comprised of an admixture of: (1) collagen; and glycan, wherein the glycosaminoglycan (2) a minor amount of a glycosaminoglycan, is chemotactic for fibroblasts or endothelial cells and the collagen is not covalently crosslinked to the glycosaminoglycan, wherein the suspension of the fibrils is applied repeatedly to the wound surface during the healing to effectively promote the healing process.
Claim 16
Independent Claim
81 words
A method for promoting the healing of a surface wound, which method comprises, applying to the wound surface a suspension of fibrils, itself comprised of an admixture of: (1) collagen; and glycan, wherein the glycosaminoglycan (2) a minor amount of a glycosaminoglycan, is chemotactic for fibroblasts or endothelial cells and the collagen is not covalently crosslinked to the glycosaminoglycan, wherein the suspension of the fibrils is applied repeatedly to the wound surface during the healing to effectively promote the healing process.
Claim 17
Dependent Claim
16 words
The method of claim 14 wherein the suspension of fibrils is a liquid suspension of fibrils.
Claim 18
Dependent Claim
15 words
The method of claim 15 wherein the liquid suspension of fibrils is an aqueous suspension.
Claim 19
Independent Claim
83 words
A method for promoting the healing of a surface wound, which method comprises, applying to the wound surface a suspension of fibrils, itself consisting essentially of an admixture of: (1) collagen; and (2) a minor amount of a glycosaminoglyclan, wherein the glycosaminoglycan is chemotactic for fibroblasts or endothelial cells and the collagen is not covalently crosslinked to the glycosaminoglycan, wherein additional suspension of particles is applied a number of times to the wound surface during the healing to effectively control the healing process.
Claim 20
Independent Claim
83 words
A method for promoting the healing of a surface wound, which method comprises, applying to the wound surface a suspension of fibrils, itself consisting essentially of an admixture of: (1) collagen; and (2) a minor amount of a glycosaminoglyclan, wherein the glycosaminoglycan is chemotactic for fibroblasts or endothelial cells and the collagen is not covalently crosslinked to the glycosaminoglycan, wherein additional suspension of particles is applied a number of times to the wound surface during the healing to effectively control the healing process.
Claim 21
Dependent Claim
16 words
The method of claim 17 wherein the suspension of particles is a liquid suspension of fibrils.
Claim 22
Dependent Claim
15 words
The method of claim 18 wherein the liquid suspension of fibrils is an aqueous suspension.
Claim 23
Independent Claim
103 words
A method for promoting the healing of a surface wound, which method comprises, applying to the wound surface a suspension of fibrils, itself comprised of an admixture of: (1) a major amount of collagen, wherein the collagen is selected from collagen fibrils which is not covalently crosslinked or from collagen which is lightly covalently crosslinked; and (2) a minor amount of glycosaminoglycan, wherein the glycosaminoglycan is chemotactic for fibroblasts or endothelial cells and the collagen is not covalently crosslinked to the glycosaminoglycan, wherein additional suspension of fibrils is applied repeatedly to the wound surface during the healing to effectively promote the healing process.
Claim 24
Independent Claim
103 words
A method for promoting the healing of a surface wound, which method comprises, applying to the wound surface a suspension of fibrils, itself comprised of an admixture of: (1) a major amount of collagen, wherein the collagen is selected from collagen fibrils which is not covalently crosslinked or from collagen which is lightly covalently crosslinked; and (2) a minor amount of glycosaminoglycan, wherein the glycosaminoglycan is chemotactic for fibroblasts or endothelial cells and the collagen is not covalently crosslinked to the glycosaminoglycan, wherein additional suspension of fibrils is applied repeatedly to the wound surface during the healing to effectively promote the healing process.
Claim 25
Dependent Claim
16 words
The method of claim 20 wherein the suspension of fibrils is a liquid suspension of fibrils.
Claim 26
Dependent Claim
15 words
The method of claim 21 wherein the liquid suspension of fibrils is an aqueous suspension.
Claim 27
Independent Claim
103 words
A method for promoting the healing of a surface wound which method comprises: applying repeatedly to the wound surface a liquid aqueous suspension of of collagen fibrils in admixture with glycosaminoglycan wherein said glycosaminoglycan is chemotactic for fibroblasts or endothelial cells and the collagen is not covalently crosslinked to the glycosaminoglycan, wherein the amounts of collagen and glycosaminoglycan in the suspension are sufficient to promote healing, wherein the amount of collagen is below that which produces an inhibition of the migration of the cells into the wound area, and the amount of glycosaminoglycan is below that which produces undesirable local inflammation or hemorrhaging.
Claim 28
Independent Claim
103 words
A method for promoting the healing of a surface wound which method comprises: applying repeatedly to the wound surface a liquid aqueous suspension of of collagen fibrils in admixture with glycosaminoglycan wherein said glycosaminoglycan is chemotactic for fibroblasts or endothelial cells and the collagen is not covalently crosslinked to the glycosaminoglycan, wherein the amounts of collagen and glycosaminoglycan in the suspension are sufficient to promote healing, wherein the amount of collagen is below that which produces an inhibition of the migration of the cells into the wound area, and the amount of glycosaminoglycan is below that which produces undesirable local inflammation or hemorrhaging.
Claim 29
Independent Claim
122 words
A method for promoting the healing of a surface wound, which method comprises, applying repeatedly to the wound surface a suspension of fibrils, itself comprised of an admixture of: (1) collagen fibrils; and (2) a glycosaminoglycan, wherein the glycosaminoglycan is chemotactic for fibroblasts or endothelial cells and the collagen is not covalently crosslinked to the glycosaminoglycan, wherein the suspension of fibrils is applied repeatedly to the wound surface during the healing process, wherein the amounts of collagen and glycosaminoglycan in the suspension are sufficient to promote healing, the amount of collagen is below that which produces an inhibition of the migration of the cells into the wound area, and the amount glycosaminoglycan is below that which produces undesirable local inflammation or hemorrhaging.
Claim 30
Independent Claim
122 words
A method for promoting the healing of a surface wound, which method comprises, applying repeatedly to the wound surface a suspension of fibrils, itself comprised of an admixture of: (1) collagen fibrils; and (2) a glycosaminoglycan, wherein the glycosaminoglycan is chemotactic for fibroblasts or endothelial cells and the collagen is not covalently crosslinked to the glycosaminoglycan, wherein the suspension of fibrils is applied repeatedly to the wound surface during the healing process, wherein the amounts of collagen and glycosaminoglycan in the suspension are sufficient to promote healing, the amount of collagen is below that which produces an inhibition of the migration of the cells into the wound area, and the amount glycosaminoglycan is below that which produces undesirable local inflammation or hemorrhaging.
Claim 31
Dependent Claim
54 words
A composition for use in promoting the healing of a surface wound, comprising a liquid aqueous suspension of a major amount of fibrils of collagen, in admixture with a minor amount of a glycosaminoglycan that exhibits a chemotactic effect on fibroblasts or endothelial cells, wherein the collagen is not covalently crosslinked to the glycosaminoglylcan.
Claim 32
Dependent Claim
54 words
A composition for use in promoting the healing of a surface wound, comprising a liquid aqueous suspension of a major amount of fibrils of collagen, in admixture with a minor amount of a glycosaminoglycan that exhibits a chemotactic effect on fibroblasts or endothelial cells, wherein the collagen is not covalently crosslinked to the glycosaminoglylcan.
Claim 33
Dependent Claim
15 words
The composition of claim 25 wherein two or more glycosaminoglycans are present in the suspension.
Claim 34
Dependent Claim
15 words
The composition of claim 26 wherein heparin and alginate are admixed together in the suspension.
Claim 35
Dependent Claim
13 words
The composition of claim 25 wherein normal saline solution is the suspending component.
Claim 36
Dependent Claim
11 words
The composition of claim 25 wherein the aqueous suspension is gelled.
Claim 37
Dependent Claim
65 words
A composition for use in promoting the healing of a surface wound, comprising a liquid aqueous suspension of fibrils of collagen in admixture with a glycosaminoglycan that exhibits a chemotactic effect on fibroblasts or endothelial cells, wherein the collagen is not covalently crosslinked to the glycosaminoglycan and the collagen is present in the suspension at a concentration of about 7 to 10 milligrams per milliliter.
Claim 38
Dependent Claim
65 words
A composition for use in promoting the healing of a surface wound, comprising a liquid aqueous suspension of fibrils of collagen in admixture with a glycosaminoglycan that exhibits a chemotactic effect on fibroblasts or endothelial cells, wherein the collagen is not covalently crosslinked to the glycosaminoglycan and the collagen is present in the suspension at a concentration of about 7 to 10 milligrams per milliliter.
Claim 39
Dependent Claim
67 words
A composition for use in promoting the healing of a surface wound, comprising a liquid aqueous suspension of fibrils of collagen, in admixture with a glycosaminoglycan that exhibits a chemotactic effect on fibroblasts or endothelial cells, wherein the collagen is not covalently crosslinked to the glycosaminoglycan, and the glycosaminoglycan is present in the suspension at a concentration of from about 100 to about 1000 micrograms per milliliter.
Claim 40
Dependent Claim
67 words
A composition for use in promoting the healing of a surface wound, comprising a liquid aqueous suspension of fibrils of collagen, in admixture with a glycosaminoglycan that exhibits a chemotactic effect on fibroblasts or endothelial cells, wherein the collagen is not covalently crosslinked to the glycosaminoglycan, and the glycosaminoglycan is present in the suspension at a concentration of from about 100 to about 1000 micrograms per milliliter.
Claim 41
Dependent Claim
64 words
A composition for use in promoting the healing of a surface wound, comprising a liquid aqueous suspension of fibrils of collagen in admixture with a glycosaminoglycan that exhibits a chemotactic effect on fibroblasts or endothelial cells, wherein the collagen is not covalently crosslinked to the glycosaminoglycan, and the glycosaminoglycan is present in the suspension at a concentration of about several hundred micrograms per milliliter.
Claim 42
Dependent Claim
64 words
A composition for use in promoting the healing of a surface wound, comprising a liquid aqueous suspension of fibrils of collagen in admixture with a glycosaminoglycan that exhibits a chemotactic effect on fibroblasts or endothelial cells, wherein the collagen is not covalently crosslinked to the glycosaminoglycan, and the glycosaminoglycan is present in the suspension at a concentration of about several hundred micrograms per milliliter.
Claim 43
Dependent Claim
66 words
A composition for use in promoting the healing of a surface wound, comprising a liquid aqueous suspension of fibrils of collagen in admixture with a glycosaminoglycan that exhibits a chemotactic effect on fibroblasts or endothelial cells, wherein the collagen is not covalently crosslinked to the glycosaminoglycan, and the ratio of the concentration of collagen to the concentration of glycosaminoglycan is about 25-35 to 1 by weight.
Claim 44
Dependent Claim
66 words
A composition for use in promoting the healing of a surface wound, comprising a liquid aqueous suspension of fibrils of collagen in admixture with a glycosaminoglycan that exhibits a chemotactic effect on fibroblasts or endothelial cells, wherein the collagen is not covalently crosslinked to the glycosaminoglycan, and the ratio of the concentration of collagen to the concentration of glycosaminoglycan is about 25-35 to 1 by weight.
Claim 45
Dependent Claim
10 words
The composition of claim 33 wherein the glycosaminoglycan is heparin.
Claim 46
Dependent Claim
11 words
The composition of claim 33 wherein the glycosaminoglycan is heparan sulfate.
Claim 47
Dependent Claim
11 words
The composition of claim 33 wherein the glycosaminoglycan is an alginate.
Claim 48
Dependent Claim
41 words
A composition comprising a major amount of collagen in fibril form, in admixture with a minor amount of heparin, and sufficient water or saline to suspend the collagen and the heparin, wherein the collagen is not covalently crosslinked to the heparin.
Claim 49
Dependent Claim
41 words
A composition comprising a major amount of collagen in fibril form, in admixture with a minor amount of heparin, and sufficient water or saline to suspend the collagen and the heparin, wherein the collagen is not covalently crosslinked to the heparin.
Claim 50
Dependent Claim
15 words
The composition of claim 37 wherein the composition is chemotactic for fibroblasts or endothelial cells.
Claim 51
Dependent Claim
25 words
The composition of claim 37 wherein collagen is present at about 7-10 milligrams per milliliter and heparin is present at about 250-350 micrograms per milliliter.
Claim 52
Dependent Claim
31 words
A composition comprising a major amount of collagen in fibril form in admixture with a minor amount of an alginate, and sufficient water or saline to suspend the collagen and alginate.
Claim 53
Dependent Claim
31 words
A composition comprising a major amount of collagen in fibril form in admixture with a minor amount of an alginate, and sufficient water or saline to suspend the collagen and alginate.
Claim 54
Dependent Claim
15 words
The composition of claim 40 wherein the composition is chemotactic for fibroblasts or endothelial cells.
Claim 55
Dependent Claim
26 words
The composition of claim 40 wherein collagen is present at about 7-10 milligrams per milliliter and the alginate is present at about 250-350 micrograms per milliliter.
Claim 56
Dependent Claim
48 words
A composition comprising a major amount of collagen in fibril form in admixture with a minor amount of a combination of heparin and alginate, and sufficient water or saline to crosslinked to the heparin and alginate wherein the collagen is not covalently suspend the collagen, heparin and alginate.
Claim 57
Dependent Claim
48 words
A composition comprising a major amount of collagen in fibril form in admixture with a minor amount of a combination of heparin and alginate, and sufficient water or saline to crosslinked to the heparin and alginate wherein the collagen is not covalently suspend the collagen, heparin and alginate.
Claim 58
Dependent Claim
15 words
The composition of claim 43 wherein the composition is chemotactic for fibroblasts or endothelial cells.
Claim 59
Dependent Claim
32 words
The composition of claim 32 wherein collagen is present at about 7-10 milligrams per milliliter and the heparin and alginate are present in a combined total of about 250-350 micrograms per milliliter.
Claim 60
Dependent Claim
73 words
A composition comprising collagen in fibril form in admixture with glycosaminoglycan, wherein the collagen is not covalently crosslinked to the glycosaminoglyclan, wherein the amounts of collagen and glycosaminoglycan in the suspension are sufficient to promote healing, the amount of collagen is below that which produces an inhibition of the migration of the cells into the wound area, and the amount of glycosaminoglycan is below that amount which produces undesirable local inflammation or hemorrhaging.
Claim 61
Dependent Claim
73 words
A composition comprising collagen in fibril form in admixture with glycosaminoglycan, wherein the collagen is not covalently crosslinked to the glycosaminoglyclan, wherein the amounts of collagen and glycosaminoglycan in the suspension are sufficient to promote healing, the amount of collagen is below that which produces an inhibition of the migration of the cells into the wound area, and the amount of glycosaminoglycan is below that amount which produces undesirable local inflammation or hemorrhaging.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1991-05-17 | 1991-11-16 | 1992-05-17 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-05-17 | 1995-11-16 | 1996-05-17 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-05-17 | 1999-11-16 | 2000-05-17 | $7700.00 | Window Closed / Lapsed |