Patent US5529914A successfully refreshed from Google Patents.
US5529914A
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Gels for encapsulation of biological materials
Assignee: The University of Texas System
•
Filing: 1992-10-07
•
Granted: 1996-06-25
•
Expires: 2012-10-07
Abstract
Abstract This invention provides novel methods for the formation of biocompatible membranes around biological materials using photopolymerization of water soluble molecules. The membranes can be used as a covering to encapsulate biological materials or biomedical devices, as a "glue" to cause more than one biological substance to adhere together, or as carriers for biologically active species. Several methods for forming these membranes are provided. Each of these methods utilizes a polymerization system containing water-soluble macromers, species which are at once polymers and macromolecules capable of further polymerization. The macromers are polymerized using a photoinitiator (such as a dye), optionally a cocatalyst, optionally an accelerator, and radiation in the form of visible or long wavelength UV light. The reaction occurs either by suspension polymerization or by interfacial polymerization. The polymer membrane can be formed directly on the surface of the biological material, or it can be formed on material which is already encapsulated.
Inventors
- 👤 Jeffrey A. Hubbell
- 👤 Chandrashekhar P. Pathak
- 👤 Amarpreet S. Sawhney
- 👤 Neil P. Desai
- 👤 Syed F. A. Hossainy
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 09:33
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61L; A61L27/00; A61L27/36; A61K38/00; A61K38/16; A61K38/41; A61K38/42; A61K38/43; A61K38/44; A61K47/00; A61K47/50; A61K47/51; A61K47/62; A61K47/64; A61K47/645; A61K47/69; A61K47/6921; A61K47/6925; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1635; A61K9/1641; A61K9/1647; A61K9/5005; A61K9/5021; A61K9/5031; A61K9/5073; A61L24/00; A61L24/001; A61L24/0031; A61L24/0042; A61L24/04; A61L24/046; A61L26/00; A61L26/0009; A61L26/0019; A61L27/28; A61L27/34; A61L27/3683; A61L27/38; A61L27/3804; A61L27/50; A61L27/52; A61L29/00; A61L29/08; A61L29/085; A61L31/00; A61L31/08; A61L31/10; A61L31/14; A61L31/145; A61L31/148; C; C08; C08F; C08F290/00; C08F290/02; C08F290/06; C08F290/062; 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; A61K35/00; A61K35/12; A61K2035/126; A61K2035/128; C12N2533/00; C12N2533/30; C12N2533/32; C12N2533/40; C12N2533/70; C12N2533/74
Claims Analysis
Total Claims: 71
Claim 1
Independent Claim
79 words
A method for encapsulation of biological material comprising the steps of a) mixing the biological material in an aqueous macromer solution comprising macromer and photoinitiator, said biological material selected from the group consisting of tissue, cells, subcellular organelles and subcellular non-organelle components, said macromer comprising a water soluble polymer having at least two sites of unsaturation; b) forming small geometric shapes of the mix in (a); and c) polymerizing the macromer by exposing the geometric shapes to light radiation.
Claim 2
Independent Claim
79 words
A method for encapsulation of biological material comprising the steps of a) mixing the biological material in an aqueous macromer solution comprising macromer and photoinitiator, said biological material selected from the group consisting of tissue, cells, subcellular organelles and subcellular non-organelle components, said macromer comprising a water soluble polymer having at least two sites of unsaturation; b) forming small geometric shapes of the mix in (a); and c) polymerizing the macromer by exposing the geometric shapes to light radiation.
Claim 3
Dependent Claim
15 words
The method of claim 1 wherein the biological material is first encapsulated in a microcapsule.
Claim 4
Dependent Claim
37 words
The method of claim 1 wherein the macromer is selected from the group consisting of ethylenically unsaturated derivatives of poly(ethylene oxide) (PEO), poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), poly(vinylpyrrolidone) (PVP), poly(ethyloxazoline) (PEOX), poly(amino acids), polysaccharides, and proteins.
Claim 5
Dependent Claim
11 words
The method of claim 3 wherein the PEG is PEG multiacrylate.
Claim 6
Dependent Claim
19 words
The method of claim 4 wherein the PEG is PEG tetraacrylate which has a molecular weight around 18,500 D.
Claim 7
Dependent Claim
41 words
The method of claim 3 wherein the polysaccharides are selected from the group consisting of alginate, hyaluronic acid, chondroitin sulfate, dextran, dextran sulfate, heparin, heparin sulfate, heparan sulfate, chitosan, gellan gum, xanthan gum, guar gum, water soluble cellulose derivatives and carrageenan.
Claim 8
Dependent Claim
19 words
The method of claim 3 wherein the proteins are selected from the group consisting of gelatin, collagen and albumin.
Claim 9
Dependent Claim
59 words
The method of claim 1 wherein the macromer is of the formula ##STR4## where F 1 =CONH, COO or NHCOO X=H, CH 3 , C 2 H 5 , C 6 H 5 , Cl, Br, OH or CH 2 COOH F 2 =COO, CONH, O or C 6 H 4 , R=CH 2 or -alkyl-, n≧5, and m≧2.
Claim 10
Dependent Claim
45 words
The method of claim 1 wherein the photoinitiator is any dye which absorbs light having frequency between 320 nm and 900 nm, can form free radicals, is at least partially water soluble, and is non-toxic to the biological material at the concentration used for polymerization.
Claim 11
Dependent Claim
19 words
The method of claim 9 wherein the photoinitiator is selected from the group consisting of 2,2-dimethoxy,2-phenylacetophenone and 2-methoxy, 2-phenylacetophenone.
Claim 12
Dependent Claim
41 words
The method of claim 1 wherein the macromer solution further comprises a cocatalyst and the photoinitiator is selected from the group consisting of ethyl eosin, eosin Y, fluorescein, 2,2-dimethoxy,2-phenylacetophenone,2-methoxy,2-phenylacetophenone, camphorquinone, rose bengal, methylene blue, erythrosin, phloxime, thionine, riboflavin and methylene green.
Claim 13
Dependent Claim
20 words
The method of claim 11 wherein the cocatalyst is a nitrogen based compound capable of stimulating a free radical reaction.
Claim 14
Dependent Claim
15 words
The method of claim 11 wherein the cocatalyst is a a nitrogen atom-containing electron-rich molecule.
Claim 15
Dependent Claim
16 words
The method of claim 11 wherein the cocatalyst is a primary, secondary, tertiary or quaternary amine.
Claim 16
Dependent Claim
39 words
The method of claim 14 wherein the cocatalyst is selected from the group consisting of triethanolamine, triethylamine, ethanolamine, N-methyl diethanolamine, N,N-dimethyl benzylamine, dibenzyl amine, N-benzyl ethanolamine, N-isopropyl benzylamine, tetramethyl ethylenediamine, potassium persulfate, tetramethyl ethylenediamine, lysine, ornithine, histidine and arginine.
Claim 17
Dependent Claim
17 words
The method of claim 1 wherein the radiation has a wavelength between 320 nm and 900 nm.
Claim 18
Dependent Claim
17 words
The method of claim 16 wherein the radiation has a wavelength between 350 nm and 700 nm.
Claim 19
Dependent Claim
24 words
The method of claim 2 wherein the microcapsule is comprised of ionically coagulatable or thermally coagulatable polymers which are non-toxic to the encapsulated material.
Claim 20
Dependent Claim
15 words
The method of claim 1 wherein the cells are primary cells or established cell lines.
Claim 21
Dependent Claim
43 words
The method of claim 1 wherein the biological material is selected from pancreatic islet cells, human foreskin fibroblasts, Chinese hamster ovary cells, beta cell insulomas, lymphoblastic leukemia cells, mouse 3T3 fibroblasts, dopamine secreting ventral mesencephalon cells, neuroblastoid cells, adrenal medulla cells, and T-cells.
Claim 22
Dependent Claim
12 words
The method of claim 18 wherein the microcapsule is comprised of alginate.
Claim 23
Dependent Claim
12 words
The method of claim 18 wherein the microcapsule is comprised of chitosan.
Claim 24
Dependent Claim
12 words
The method of claim 18 wherein the microcapsule is comprised of agarose.
Claim 25
Dependent Claim
12 words
The method of claim 18 wherein the microcapsule is comprised of gelatin.
Claim 26
Dependent Claim
34 words
The method of claim 1 wherein the geometric shapes are formed by coextrusion of the aqueous macromer solution mixed with the biological material with a non-toxic, non-immunogenic, non-miscible substance capable of maintaining droplet formation.
Claim 27
Dependent Claim
11 words
The method of claim 25 wherein the non-miscible substance is oil.
Claim 28
Dependent Claim
11 words
The method of claim 26 wherein the oil is mineral oil.
Claim 29
Dependent Claim
25 words
The method of claim 1 wherein the geometric shapes are formed by coextrusion of the aqueous macromer solution mixed with the biological material in air.
Claim 30
Dependent Claim
29 words
The method of claim 1 wherein the geometric shapes are formed by agitation of the aqueous macromer solution mixed with the biological material with a non-toxic, non-immunogenic, non-miscible substance.
Claim 31
Dependent Claim
11 words
The method of claim 29 wherein the non-miscible substance is oil.
Claim 32
Dependent Claim
19 words
The method of claim 1 wherein the macromer solution further comprises an accelerator to accelerate the rate of polymerization.
Claim 33
Dependent Claim
19 words
The method of claim 31 wherein the accelerator is a small molecule containing an allyl, vinyl or acrylate group.
Claim 34
Dependent Claim
28 words
The method of claim 32 wherein the accelerator is selected from the group consisting of N-vinyl pyrolidinone, 2-vinyl pyridine, 1-vinyl imidazole, 9-vinyl carbazole, acrylic acid and 2-allyl,2-methyl,1-3-cyclopentane dione.
Claim 35
Dependent Claim
11 words
The method of claim 33 wherein the accelerator is N-vinyl pyrolidinone.
Claim 36
Independent Claim
66 words
A method for encapsulation of biological material comprising the steps of a) coating the biological material with photoinitiator, said biological material selected from the group consisting of tissue, cells, subcellular organelles, and subcellular non-organelle components; b) suspending the coated material in an aqueous macromer solution, said macromer comprising a water soluble polymer having at least two sites of unsaturation; and c) irradiating the suspension with light.
Claim 37
Independent Claim
66 words
A method for encapsulation of biological material comprising the steps of a) coating the biological material with photoinitiator, said biological material selected from the group consisting of tissue, cells, subcellular organelles, and subcellular non-organelle components; b) suspending the coated material in an aqueous macromer solution, said macromer comprising a water soluble polymer having at least two sites of unsaturation; and c) irradiating the suspension with light.
Claim 38
Dependent Claim
37 words
The method of claim 35 wherein the macromer is selected from the group consisting of ethylenically unsaturated derivatives of poly(ethylene oxide) (PEO), poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), poly(vinylpyrrolidone) (PVP), poly(ethyloxazoline) (PEOX), poly(amino acids), polysaccharides, and proteins.
Claim 39
Dependent Claim
11 words
The method of claim 36 wherein the PEG is PEG multiacrylate.
Claim 40
Dependent Claim
19 words
The method of claim 37 wherein the PEG is PEG tetraacrylate which has a molecular weight around 18,500 D.
Claim 41
Dependent Claim
41 words
The method of claim 36 wherein the polysaccharides are selected from the group consisting of alginate, hyaluronic acid, chondroitin sulfate, dextran, dextran sulfate, heparin, heparin sulfate, heparan sulfate, chitosan, gellan gum, xanthan gum, guar gum, water soluble cellulose derivatives and carrageenan.
Claim 42
Dependent Claim
19 words
The method of claim 36 wherein the proteins are selected from the group consisting of gelatin, collagen and albumin.
Claim 43
Dependent Claim
59 words
The method of claim 35 wherein the macromer is of the formula ##STR5## where F 1 =CONH, COO or NHCOO X=H, CH 3 , C 2 H 5 , C 6 H 5 , Cl, Br, OH or CH 2 COOH F 2 =COO, CONH, O or C 6 H 4 , R=CH 2 or -alkyl-, n≧5, and m≧2.
Claim 44
Dependent Claim
45 words
The method of claim 35 wherein the photoinitiator is any dye which absorbs light having frequency between 320 nm and 900 nm, can form free radicals, is at least partially water soluble, and is non-toxic to the biological material at the concentration used for polymerization.
Claim 45
Dependent Claim
18 words
The method of claim 42 wherein the photoinitiator is selected from the group consisting of 2,2-dimethoxy,2-phenylacetophenone and 2-methoxy,2-phenylacetophenone.
Claim 46
Dependent Claim
40 words
The method of claim 35 wherein the macromer solution further comprises a cocatalyst and the photoinitiator is selected from the group consisting of ethyl eosin, eosin Y, fluorescein,2,2-dimethoxy,2-phenylacetophenone,2-methoxy,2-phenylacetophenone, camphorquinone, rose bengal, methylene blue, erythrosin, phloxime, thionine, riboflavin and methylene green.
Claim 47
Dependent Claim
20 words
The method of claim 44 wherein the cocatalyst is a nitrogen based compound capable of stimulating a free radical reaction.
Claim 48
Dependent Claim
15 words
The method of claim 44 wherein the cocatalyst is a a nitrogen atom-containing electron-rich molecule.
Claim 49
Dependent Claim
16 words
The method of claim 44 wherein the cocatalyst is a primary, secondary, tertiary or quaternary amine.
Claim 50
Dependent Claim
39 words
The method of claim 47 wherein the cocatalyst is selected from the group consisting of triethanolamine, triethylamine, ethanolamine, N-methyl diethanolamine, N,N-dimethyl benzylamine, dibenzyl amine, N-benzyl ethanolamine, N-isopropyl benzylamine, tetramethyl ethylenediamine, potassium persulfate, tetramethyl ethylenediamine, lysine, ornithine, histidine and arginine.
Claim 51
Dependent Claim
17 words
The method of claim 35 wherein the radiation has a wavelength between 320 nm and 900 nm.
Claim 52
Dependent Claim
17 words
The method of claim 49 wherein the radiation has a wavelength between 350 nm and 700 nm.
Claim 53
Dependent Claim
15 words
The method of claim 35 wherein the cells are primary cells or established cell lines.
Claim 54
Dependent Claim
43 words
The method of claim 35 wherein the biological material is selected from pancreatic islet cells, human foreskin fibroblasts, Chinese hamster ovary cells, beta cell insulomas, lymphoblastic leukemia cells, mouse 3T3 fibroblasts, dopamine secreting ventral mesencephalon cells, neuroblastoid cells, adrenal medulla cells, and T-cells.
Claim 55
Dependent Claim
34 words
The method of claim 35 wherein the geometric shapes are formed by coextrusion of the aqueous macromer solution mixed with the biological material with a non-toxic, non-immunogenic, non-miscible substance capable of maintaining droplet formation.
Claim 56
Dependent Claim
11 words
The method of claim 53 wherein the non-miscible substance is oil.
Claim 57
Dependent Claim
11 words
The method of claim 54 wherein the oil is mineral oil.
Claim 58
Dependent Claim
25 words
The method of claim 35 wherein the geometric shapes are formed by coextrusion of the aqueous macromer solution mixed with the biological material in air.
Claim 59
Dependent Claim
29 words
The method of claim 35 wherein the geometric shapes are formed by agitation of the aqueous macromer solution mixed with the biological material with a non-toxic, non-immunogenic, non-miscible substance.
Claim 60
Dependent Claim
11 words
The method of claim 57 wherein the non-miscible substance is oil.
Claim 61
Dependent Claim
15 words
The method of claim 35 wherein the biological material is first encapsulated in a microcapsule.
Claim 62
Dependent Claim
24 words
The method of claim 59 wherein the microcapsule is comprised of ionically coagulatable or thermally coagulatable polymers which are non-toxic to the encapsulated material.
Claim 63
Dependent Claim
12 words
The method of claim 60 wherein the microcapsule is comprised of alginate.
Claim 64
Dependent Claim
12 words
The method of claim 60 wherein the microcapsule is comprised of chitosan.
Claim 65
Dependent Claim
12 words
The method of claim 60 wherein the microcapsule is comprised of agarose.
Claim 66
Dependent Claim
12 words
The method of claim 60 wherein the microcapsule is comprised of gelatin.
Claim 67
Dependent Claim
19 words
The method of claim 35 wherein the macromer solution further comprises an accelerator to accelerate the rate of polymerization.
Claim 68
Dependent Claim
19 words
The method of claim 65 wherein the accelerator is a small molecule containing an allyl, vinyl or acrylate group.
Claim 69
Dependent Claim
28 words
The method of claim 66 wherein the accelerator is selected from the group consisting of N-vinyl pyrolidinone, 2-vinyl pyridine, 1-vinyl imidazole, 9-vinyl carbazole, acrylic acid and 2-allyl,2-methyl,1-3-cyclopentane dione.
Claim 70
Dependent Claim
11 words
The method of claim 67 wherein the accelerator is N-vinyl pyrolidinone.
Claim 71
Dependent Claim
24 words
The method of claim 31 wherein the macromer is poly(ethylene glycol) (PEG), the biological material is mammalian cells, and the accelerator is N-vinyl pyrrolidinone.
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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) | 1999-06-25 | 1999-12-25 | 2000-06-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2003-06-25 | 2003-12-25 | 2004-06-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-06-25 | 2007-12-25 | 2008-06-25 | $7700.00 | Window Closed / Lapsed |