US5626863A
Expired / Lapsed
US
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Photopolymerizable biodegradable hydrogels as tissue contacting materials and controlled-release carriers
Assignee: The University of Texas System
•
Filing: 1995-01-27
•
Granted: 1997-05-06
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Expires: 2015-01-27
Abstract
Abstract Hydrogels of polymerized and crosslinked macromers comprising hydrophilic oligomers having biodegradable monomeric or oligomeric extensions, which biodegradable extensions are terminated on free ends with end cap monomers or oligomers capable of polymerization and cross linking are described. The hydrophilic core itself may be degradable, thus combining the core and extension functions. Macromers are polymerized using free radical initiators under the influence of long wavelength ultraviolet light, visible light excitation or thermal energy. Biodegradation occurs at the linkages within the extension oligomers and results in fragments which are non-toxic and easily removed from the body. Preferred applications for the hydrogels include prevention of adhesion formation after surgical procedures, controlled release of drugs and other bioactive species, temporary protection or separation of tissue surfaces, adhering of sealing tissues together, and preventing the attachment of cells to tissue surfaces.
Inventors
- 👤 Jeffrey A. Hubbell
- 👤 Chandrashekhar P. Pathak
- 👤 Amarpreet S. Sawhney
- 👤 Neil P. Desai
- 👤 Jennifer L. Hill
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 04:03
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1635; A61K38/00; A61K38/16; A61K38/43; A61K38/46; A61K38/47; A61K38/48; A61K38/49; A61K47/00; A61K47/30; A61K47/32; A61K9/0012; A61K9/0019; A61K9/0024; A61K9/1641; A61K9/1647; A61L; A61L24/00; A61L24/001; A61L24/0031; A61L24/0042; A61L24/04; A61L24/046; A61L27/00; A61L27/28; A61L27/34; A61L27/36; A61L27/38; A61L27/50; A61L27/52; A61L29/00; A61L29/08; A61L29/085; A61L31/00; A61L31/14; A61L31/145; A61L31/148; A61L31/16; C; C08; C08F; C08F290/00; C08F290/02; C08F290/06; C08F291/00; C09; C09D; C09D153/00; C12; C12N; C12N11/00; C12N11/02; C12N11/04; C12N5/00; C12N5/0012; C12N5/06; C12N5/0602; C12N5/0676; C12N5/0677; C12Y; C12Y302/00; C12Y302/01; C12Y302/01017; C12Y304/00; C12Y304/21; C12Y304/21068; A61K35/00; A61K35/12; A61K2035/126; A61K2035/128; A61L2300/00; A61L2300/40; A61L2300/424; A61L2300/60; A61L2300/602; C12N2533/00; C12N2533/30; C12N2533/32; C12N2533/40; C12N2533/70; C12N2533/74
Claims Analysis
Total Claims: 47
Claim 1
Independent Claim
106 words
A method of forming a polymeric, biocompatible material on tissue or cells, the method comprising applying to the tissue or cells a solution of biodegradable, polymerizable macromer having a solubility of at least about 1 g/100 ml in an aqueous solution comprising at least one water soluble region, at least one degradable region which is hydrolyzable under in vivo conditions, and free radical polymerizable end groups having the capacity to form additional covalent bonds resulting in macromer interlinking, wherein the polymerizable end groups are separated from each other by at least one degradable region, in the presence of a free radical initiator, and polymerizing the macromer.
Claim 2
Independent Claim
106 words
A method of forming a polymeric, biocompatible material on tissue or cells, the method comprising applying to the tissue or cells a solution of biodegradable, polymerizable macromer having a solubility of at least about 1 g/100 ml in an aqueous solution comprising at least one water soluble region, at least one degradable region which is hydrolyzable under in vivo conditions, and free radical polymerizable end groups having the capacity to form additional covalent bonds resulting in macromer interlinking, wherein the polymerizable end groups are separated from each other by at least one degradable region, in the presence of a free radical initiator, and polymerizing the macromer.
Claim 3
Dependent Claim
20 words
The method of claim 1 wherein the tissue is coated with the polymerized macromer to inhibit the formation of adhesions.
Claim 4
Dependent Claim
33 words
The method of claim 1 wherein the method further comprises applying the macromer solution to tissue surfaces in the presence of free radical initiator and polymerizing the macromer to adhere the tissue surfaces.
Claim 5
Dependent Claim
34 words
The method of claim 1 further comprising providing with the macromer solution biologically active materials selected from the group consisting of proteins, carbohydrates, nucleic acids, inorganic biologically active materials, cells, tissues, and tissue aggregates.
Claim 6
Independent Claim
87 words
A method of forming a polymeric, biocompatible material on tissue, the method comprising: applying a free radical initiator at a tissue site; and applying to the tissue site a solution of biodegradable, polymerizable, and at least substantially water soluble macromer comprising at least one water soluble region, at least one degradable region, and at least two free radical polymerizable regions, wherein the polymerizable regions are separated from each other by at least one degradable region, and polymerizing the macromer in the presence of the free radical initiator.
Claim 7
Independent Claim
87 words
A method of forming a polymeric, biocompatible material on tissue, the method comprising: applying a free radical initiator at a tissue site; and applying to the tissue site a solution of biodegradable, polymerizable, and at least substantially water soluble macromer comprising at least one water soluble region, at least one degradable region, and at least two free radical polymerizable regions, wherein the polymerizable regions are separated from each other by at least one degradable region, and polymerizing the macromer in the presence of the free radical initiator.
Claim 8
Independent Claim
104 words
A method of forming a polymeric, biocompatible material on tissue, the method comprising: applying a free radical initiator to a tissue site, permitting the initiator to bind to the tissue, and removing unbound initiator; applying to the tissue site, after removal of the unbound initiator, a solution of biodegradable, polymerizable, and at least substantially water soluble macromer comprising at least one water soluble region, at least one degradable region, and at least two free radical polymerizable regions, wherein the polymerizable regions are separated from each other by at least one degradable region, and polymerizing the macromer in the presence of the free radical initiator.
Claim 9
Independent Claim
104 words
A method of forming a polymeric, biocompatible material on tissue, the method comprising: applying a free radical initiator to a tissue site, permitting the initiator to bind to the tissue, and removing unbound initiator; applying to the tissue site, after removal of the unbound initiator, a solution of biodegradable, polymerizable, and at least substantially water soluble macromer comprising at least one water soluble region, at least one degradable region, and at least two free radical polymerizable regions, wherein the polymerizable regions are separated from each other by at least one degradable region, and polymerizing the macromer in the presence of the free radical initiator.
Claim 10
Dependent Claim
41 words
The method of claim 1 further comprising providing with the macromer solution biologically active molecules selected from the group consisting of enzymes, antibiotics, antineoplastic agents, local anesthetics, hormones, antiangiogenic agents, antibodies, neurotransmitters, psychoactive drugs, drugs affecting reproductive organs, and antisense oligonucleotides.
Claim 11
Dependent Claim
56 words
The method of claim 1 wherein the macromer comprises a water soluble core region, at least two degradable extensions on the core, and an end cap on at least two of the degradable extensions, wherein the core comprises poly(ethylene glycol); each extension comprises biodegradable poly(α-hydroxy acid); and each end cap comprises an acrylate oligomer or monomer.
Claim 12
Dependent Claim
49 words
The method of claim 8 wherein the poly(ethylene glycol) has a molecular weight between about 400 and 30,000 Da; the poly(α-hydroxy acid) oligomer has a molecular weight between about 200 and 1200 Da; and the acrylate oligomer or monomer has a molecular weight between about 50 and 200 Da.
Claim 13
Dependent Claim
26 words
The method of claim 1 wherein the degradable region is selected from the group consisting of poly(α-hydroxy acids), poly(lactones), poly(amino acids), poly(anhydrides), poly(orthoesters), poly(orthocarbonates) and poly(phosphoesters).
Claim 14
Dependent Claim
23 words
The method of claim 10 wherein the poly(α-hydroxy acid) is selected from the group consisting of poly(glycolic acid), poly(DL-lactic acid) and poly(L-lactic acid).
Claim 15
Dependent Claim
19 words
The method of claim 10 wherein the poly(lactone) is selected from the group consisting of poly(ε-caprolactone), poly(δ-valerolactone), and poly(gamma-butyrolactone).
Claim 16
Dependent Claim
35 words
The method of claim 1 wherein the water soluble region is selected from the group consisting of poly(ethylene glycol), poly(ethylene oxide), poly(vinyl alcohol), poly(vinylpyrrolidone), poly(ethyloxazoline), poly(ethylene oxide)-co-poly(propyleneoxide) block copolymers, polysaccharides, carbohydrates, proteins, and combinations thereof.
Claim 17
Dependent Claim
22 words
The method of claim 1 wherein the polymerizable end groups contain a carbon-carbon double bond capable of cross-linking and polymerizing the macromers.
Claim 18
Dependent Claim
21 words
The method of claim 1 wherein the macromer is polymerized to form a coating on the tissue thereby to inhibit restenosis.
Claim 19
Dependent Claim
25 words
The method of claim 1 wherein the macromer is polymerized to form a coating on the tissue thereby to form a sealant on the tissue.
Claim 20
Dependent Claim
48 words
The method of claim 1, wherein the macromer is characterized in that the water soluble region is attached to a degradable region, at least one polymerizable end group is attached to the water soluble region, and at least one polymerizable end group is attached to the degradable region.
Claim 21
Dependent Claim
43 words
The method of claim 1, wherein the macromer is characterized in that the water soluble region forms a central core, at least two degradable regions are attached to the core, and at least two polymerizable end groups are attached to the degradable regions.
Claim 22
Dependent Claim
44 words
The method of claim 1, wherein the macromer is characterized in that the degradable region is a central core, at least two water soluble regions are attached to the core, and at least one polymerizable end group is attached to each water soluble region.
Claim 23
Dependent Claim
46 words
The method of claim 1, wherein the macromer is characterized in that the water soluble region is a macromer backbone, the degradable region is a branch or graft attached to the macromer backbone, and at least two polymerizable end groups are attached to the degradable regions.
Claim 24
Dependent Claim
49 words
The method of claim 1, wherein the macromer is characterized in that the degradable region is a macromer backbone, the water soluble region is a branch or graft attached to the degradable backbone, and two or more polymerizable end groups are attached to the water soluble branches or grafts.
Claim 25
Dependent Claim
50 words
The method of claim 1, wherein the macromer is characterized in that the water soluble region is a star backbone, the degradable region is a branch or graft attached to the water soluble star backbone, and at least two polymerizable end groups are attached to a degradable branch or graft.
Claim 26
Dependent Claim
50 words
The method of claim 1, wherein the macromer is characterized in that the degradable region is a star backbone, the water soluble region is a branch or graft attached to the degradable star backbone, and two or more polymerizable end groups are attached to the water soluble branch or graft.
Claim 27
Dependent Claim
21 words
The method of claim 1, wherein the macromer is characterized in that the water soluble region is also the degradable region.
Claim 28
Dependent Claim
37 words
The method of claim 1, wherein the macromer is characterized in that the water soluble region is also the degradable region, and one or more additional degradable regions are grafts or branches upon the water soluble region.
Claim 29
Dependent Claim
33 words
The method of claim 1 wherein crosslinking and polymerization of the macromer can be initiated by a light-sensitive free-radical polymerization initiator with or without a cocatalyst, further comprising a free radical polymerization initiator.
Claim 30
Dependent Claim
28 words
The method of claim 26 wherein the initiator is selected from the group consisting of xanthine dyes, acridine dyes, thiazine dyes, phenazine dyes, camphorquinone dyes, and acetophenone dyes.
Claim 31
Dependent Claim
25 words
The method of claim 26 wherein the initiator is selected from the group consisting of an eosin dye with triethanolamine, 2,2-dimethyl-2-phenyl acetophenone, and 2-methoxy-2-phenyl acetophenone.
Claim 32
Dependent Claim
23 words
The method of claim 1 wherein crosslinking or polymerizations are initiated in situ by light having a wavelength of 320 nm or longer.
Claim 33
Dependent Claim
12 words
The method of claim 1 wherein the initiator is a thermal initiator.
Claim 34
Dependent Claim
13 words
The method of claim 1, wherein the initiator further comprises an initiator mixture.
Claim 35
Dependent Claim
17 words
The method of claim 1, wherein the polymerized macromer forms a barrier on the cells or tissue.
Claim 36
Dependent Claim
16 words
The method of claim 1, wherein the tissue or cell is encapsulated by the polymerized macromer.
Claim 37
Dependent Claim
13 words
The method of claim 1, wherein the polymerized macromer comprises a tissue support.
Claim 38
Dependent Claim
20 words
The method of claim 34, wherein the support forms a shaped article within the body to serve a mechanical function.
Claim 39
Dependent Claim
33 words
The method of claim 35, wherein the support is selected from the group consisting of organ sealants, bone defect sealants, space-fillers for aneurysms, blood vessel interior coatings, vessels, tubes and organ holding strictures.
Claim 40
Dependent Claim
12 words
The method of claim 2, for inhibiting adhesions of the peritoneal cavity.
Claim 41
Dependent Claim
16 words
The method of claim 1, further comprising providing with the macromer solution biologically active organic molecules.
Claim 42
Independent Claim
93 words
A method of forming a polymeric, biocompatible material on a surface, the method comprising: applying to the surface a solution of a biodegradable, polymerizable macromer, having a solubility of at least about 1 g/100 ml in an aqueous solution, and comprising at least one water soluble region, at least one degradable region which is hydrolyzable under in vivo conditions, and free radical polymerizable end groups, wherein the polymerizable end groups are separated from each other by at least one degradable region, in the presence of a free radical initiator, and polymerizing the macromer.
Claim 43
Independent Claim
93 words
A method of forming a polymeric, biocompatible material on a surface, the method comprising: applying to the surface a solution of a biodegradable, polymerizable macromer, having a solubility of at least about 1 g/100 ml in an aqueous solution, and comprising at least one water soluble region, at least one degradable region which is hydrolyzable under in vivo conditions, and free radical polymerizable end groups, wherein the polymerizable end groups are separated from each other by at least one degradable region, in the presence of a free radical initiator, and polymerizing the macromer.
Claim 44
Dependent Claim
10 words
The method of claim 39 wherein the surface comprises glass.
Claim 45
Dependent Claim
14 words
The method of claim 39, further comprising contacting the surface with cells or tissue.
Claim 46
Dependent Claim
20 words
The method of claim 41, wherein polymerized macromer forms a coating on the surface which inhibits adhesion to the surface.
Claim 47
Dependent Claim
18 words
The method of claim 42 wherein the adhesion of protein, cells or tissue to the surface is inhibited.
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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) | 2000-05-05 | 2000-11-04 | 2001-05-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-05-05 | 2004-11-04 | 2005-05-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-05-05 | 2008-11-04 | 2009-05-06 | $7700.00 | Window Closed / Lapsed |