US4925677A
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Biodegradable hydrogel matrices for the controlled release of pharmacologically active agents
Assignee: Actavis Laboratories UT Inc
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Filing: 1988-08-31
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Granted: 1990-05-15
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Expires: 2008-08-31
Abstract
Abstract A biodegradable hydrogen matrix is provided, useful for the controlled release of pharmacologically active agents. The matrix is formed by cross-linking a proteinaceous component and a polysaccharide or mucopolysaccharide, and then loading a selected drug therein. By varying temperature, ionic strength, and the composition of the hydrogel matrix, one can control degradation kinetics, the degree of uptake of a particular pharmacologically active agent, and the overall timed release profile.
Inventors
- 👤 Jan Feijen
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 04:03
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/20; A61K9/2004; A61K9/2022; A61K9/2063; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1652; A61K9/1658; A61K9/205
Claims Analysis
Total Claims: 34
Claim 1
Independent Claim
64 words
A drug delivery system comprising: (a) a biodegradable endogenous hydrogel matrix comprising a protein, a polysaccharide, and a cross-linking agent providing network linkage therebetween, wherein the weight ratio of polysaccharide to protein in the matrix is in the range of about 10:90 to 90:10; and (b) an effective amount of a drug contained within the matrix to provide the desired systemic or local effect.
Claim 2
Dependent Claim
64 words
A drug delivery system comprising: (a) a biodegradable endogenous hydrogel matrix comprising a protein, a polysaccharide, and a cross-linking agent providing network linkage therebetween, wherein the weight ratio of polysaccharide to protein in the matrix is in the range of about 10:90 to 90:10; and (b) an effective amount of a drug contained within the matrix to provide the desired systemic or local effect.
Claim 3
Dependent Claim
28 words
The drug delivery system of claim 1, wherein the protein is selected from the group consisting of albumin, casein, fibrinogen, γ-globulin, hemoglobin, ferritin, elastin and synthetic α-amino peptides.
Claim 4
Dependent Claim
29 words
The drug delivery system of claim 1, wherein the polysaccharide is selected from the group consisting of heparin, heparin fragments, heparan, heparan sulfate, chondroitin sulfate, dextran and mixtures thereof.
Claim 5
Dependent Claim
24 words
The drug delivery system of claim 3, wherein the polysaccharide is selected from the group consisting of heparin, heparin fragments, heparan and heparan sulfate.
Claim 6
Dependent Claim
12 words
The drug delivery system of claim 2, wherein the protein is albumin.
Claim 7
Dependent Claim
23 words
The drug delivery system of claim 1, wherein the ratio of polysaccharide to protein is in the range of about 10:90 to 60:40.
Claim 8
Dependent Claim
16 words
The drug delivery system of claim 1, wherein the cross-linking agent is an amide bond-forming agent.
Claim 9
Dependent Claim
15 words
The drug delivery system of claim 7, wherein the amide bond-forming agent is a carbodiimide.
Claim 10
Dependent Claim
12 words
The drug delivery system of claim 8, wherein the carbodiimide is N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide.
Claim 11
Dependent Claim
17 words
The drug delivery system of claim 1, wherein the cross-linking agent contains at least two aldehyde groups.
Claim 12
Dependent Claim
13 words
The drug delivery system of claim 10, wherein the cross-linking agent is glutaraldehyde.
Claim 13
Dependent Claim
21 words
The drug delivery system of claim 1, wherein the drug contained in the hydrogel matrix is either dissolved or dispersed therein.
Claim 14
Dependent Claim
26 words
The drug delivery system of claim 12, wherein the drug is selected from the group consisting of proteins, enzymes, mucopolysaccharides, peptides, hormones, antibodies and cytostatic agents.
Claim 15
Independent Claim
85 words
A method for making a drug delivery system, comprising: dissolving a protein and a polysaccharide in an aqueous medium wherein the weight ratio of polysaccharide to protein is in the range of 10:90 to 90:10; cross-linking the protein and polysaccharide to provide a cross-linked hydrogel matrix; and loading an effective amount of a drug in solution or in liquid form into said hydrogel matrix to a predetermined degree wherein the cross-linking is effected by admixture of the protein and polysaccharide components with a cross-linking agent.
Claim 16
Independent Claim
85 words
A method for making a drug delivery system, comprising: dissolving a protein and a polysaccharide in an aqueous medium wherein the weight ratio of polysaccharide to protein is in the range of 10:90 to 90:10; cross-linking the protein and polysaccharide to provide a cross-linked hydrogel matrix; and loading an effective amount of a drug in solution or in liquid form into said hydrogel matrix to a predetermined degree wherein the cross-linking is effected by admixture of the protein and polysaccharide components with a cross-linking agent.
Claim 17
Dependent Claim
14 words
The method of claim 14, wherein the cross-linking agent is an amide bond-forming agent.
Claim 18
Dependent Claim
13 words
The method of claim 15, wherein the amide bond-forming agent is a carbodiimide.
Claim 19
Dependent Claim
10 words
The method of claim 16, wherein the carbodiimide is N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide.
Claim 20
Dependent Claim
26 words
The method of claim 14, wherein the cross-linking agent contains at least two aldehyde groups, and wherein cross-linking is followed by reduction with NaCNBH 3 .
Claim 21
Dependent Claim
18 words
The method of claim 18, wherein the cross-linking agent is glutaraldehyde, followed by reduction with NaCNBH 3 .
Claim 22
Dependent Claim
64 words
The method of claim 14, wherein the cross-linking is effected by: (a) initially dissolving the polysaccharide as a quaternary ammonium complex component in an organic reaction medium; (b) reacting the polysaccharide component with carbonyldiimidazole to give a preactivated polysaccharide compound; (c) further reacting the preactivated polysaccharide with saccharine, followed by (d) reacting the activated polysaccharide with a selected protein dissolved in the aqueous medium.
Claim 23
Dependent Claim
27 words
The method of claim 14, wherein the protein is selected from the group consisting of albumin, casein, fibrinogen, γ-globulin, hemoglobin, ferritin and elastin and synthetic α-amino peptides.
Claim 24
Dependent Claim
10 words
The method of claim 21, wherein the protein is albumin.
Claim 25
Dependent Claim
25 words
The method of claim 14, wherein the polysaccharide is selected from the group consisting of heparin, heparin fragments, heparan, heparan sulfate, chondroitin sulfate and dextran.
Claim 26
Dependent Claim
21 words
The method of claim 14, wherein the ratio of polysaccharide to protein is in the range of about 10;90 to 60:40.
Claim 27
Dependent Claim
26 words
The method of claim 14, wherein the degree of drug loading is controlled by the ratio of polysaccharide to protein and cross-linker in the hydrogel matrix.
Claim 28
Dependent Claim
15 words
The method of claim 14, wherein the degree of drug loading is controlled by temperature.
Claim 29
Dependent Claim
16 words
The method of claim 14, wherein the degree of drug loading is controlled by ionic strength.
Claim 30
Dependent Claim
15 words
The method of claim 14, wherein the degree of drug loading is controlled by pH.
Claim 31
Independent Claim
60 words
A method of administering a drug to a patient so that release of the drug is controlled, comprising the steps of administering the drug in a biodegradable hydrogel matrix which comprises a protein, a polysaccharide, and a cross-linking agent providing network linkage therebetween, wherein the weight ratio of polysaccharide to protein is in the range of about 10:90 to 90:10.
Claim 32
Independent Claim
60 words
A method of administering a drug to a patient so that release of the drug is controlled, comprising the steps of administering the drug in a biodegradable hydrogel matrix which comprises a protein, a polysaccharide, and a cross-linking agent providing network linkage therebetween, wherein the weight ratio of polysaccharide to protein is in the range of about 10:90 to 90:10.
Claim 33
Dependent Claim
17 words
The method of claim 29, wherein the administering of the agent in the biodegradable matrix is oral.
Claim 34
Dependent Claim
17 words
The method of claim 29, wherein the administering of the agent in the biodegradable matrix is parenteral.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1993-05-14 | 1993-11-13 | 1994-05-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1997-05-14 | 1997-11-13 | 1998-05-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2001-05-14 | 2001-11-13 | 2002-05-15 | $7700.00 | Window Closed / Lapsed |