US5705270A
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US
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Microcapsules prepared from crosslinkable polysaccharides, polycations and/or lipids and use therefor
Assignee: RENEURON Inc
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Filing: 1995-06-07
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Granted: 1998-01-06
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Expires: 2015-06-07
Abstract
Abstract The present invention relates to a new form of biocompatible materials (e.g., lipids, polycations, polysaccharides) which are capable of undergoing free radical polymerization, e.g., by using certain sources of light; methods of modifying certain synthetic and naturally occurring biocompatible materials to make polymerizable microcapsules containing biological material coated with said polymerizable materials, composites of said polymerizable materials, methods of making microcapsules and encapsulating biological materials therein, and apparatus for making microcapsules containing biological cells (particularly islets of Langerhans) coated with polymerizable alginate or with a composite thereof (e.g., alginate and PEG). The present invention also relates to drug delivery systems relating to the foregoing, as well as bioadhesives and wound dressings made utilizing the foregoing technology.
Inventors
- 👤 Patrick Soon-Shiong
- 👤 Neil P. Desai
- 👤 Paul A. Sandford
- 👤 Roswitha A. Heintz
- 👤 Soebianto Sojomihardjo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 13:53
CPC Classifications
C; C08; C08F; C08F290/00; A; A61; A61F; A61F13/00; A61F13/02; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; A61K9/1273; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1635; A61K9/1652; A61L; A61L24/00; A61L24/04; A61L24/08; A61L26/00; A61L26/0009; A61L26/0023; A61L27/00; A61L27/36; A61L27/38; A61L27/3804; B; B82; B82Y; B82Y5/00; C08B; C08B37/00; C08B37/0006; C08B37/0024; C08B37/0027; C08B37/003; C08B37/006; C08B37/0063; C08B37/0072; C08B37/0084; C08F290/08; C08F290/10; A61F2013/00089; A61F2013/00157; A61F2013/00217; A61F2013/00229; A61F2013/00361; A61F2013/00544; A61F2013/00574; A61F2013/00621; A61F2013/00625; A61F2013/00638; A61F2013/00655; A61F2013/00676; A61F2013/0068; A61F2013/00727; A61F2013/00748; A61F2013/00855; A61F2013/00876; A61F2013/00902; A61F2013/00906; A61F2013/0091; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 30
Claim 1
Independent Claim
123 words
Microcapsules comprising biologically active material encapsulated in a modified biocompatible material which has been subjected to free radical polymerization under biocompatible conditions in an aqueous media that is free of organic solvents, wherein said material has the formula: A--X wherein: A is selected from the group consisting of polysaccharides, polycations and lipids, X is a moiety containing a carbon-carbon double bond or triple bond capable of free radical polymerization; and A and X are linked covalently through linkages selected from the group consisting of ester, ether, thioether, disulfide, amide, secondary amines, tertiary amines, direct C--C linkages, sulfate esters, sulfonate esters, phosphate esters, urethanes, and carbonates; and wherein the largest physical dimension of said microcapsule, including the encapsulated material, does not exceed 1 mm.
Claim 2
Dependent Claim
123 words
Microcapsules comprising biologically active material encapsulated in a modified biocompatible material which has been subjected to free radical polymerization under biocompatible conditions in an aqueous media that is free of organic solvents, wherein said material has the formula: A--X wherein: A is selected from the group consisting of polysaccharides, polycations and lipids, X is a moiety containing a carbon-carbon double bond or triple bond capable of free radical polymerization; and A and X are linked covalently through linkages selected from the group consisting of ester, ether, thioether, disulfide, amide, secondary amines, tertiary amines, direct C--C linkages, sulfate esters, sulfonate esters, phosphate esters, urethanes, and carbonates; and wherein the largest physical dimension of said microcapsule, including the encapsulated material, does not exceed 1 mm.
Claim 3
Dependent Claim
31 words
The microcapsules of claim 1 wherein said biologically active material is: individual living cells or groups of living cells; at least one pharmacologically active drug; or at least one diagnostic agent.
Claim 4
Dependent Claim
13 words
The microcapsules of claim 2 wherein said living cells comprise islets of Langerhans.
Claim 5
Dependent Claim
98 words
The microcapsules of claim 1, wherein A is further covalently linked to Y, wherein Y is an alkylene glycol, polyalkylene glycol, or hydrophobic onium cation, wherein the linkage between Y and A is selected from the group consisting of the covalent linkages ester, ether, thioether, disulfide, amide, secondary amines, tertiary amines, direct C--C linkages, sulfate esters, sulfonate esters, phosphate esters, urethanes, and carbonates; or said linkage between Y and A is the ionic linkage ##STR9## wherein Q is nitrogen or phosphorus, and R is hydrogen, an alkyl radical, an aryl radical, an alkaryl radical, or an aralkyl radical.
Claim 6
Dependent Claim
49 words
The microcapsules of claim 4, wherein A is a polysaccharide selected from the group consisting of alginate, high M-content alginate, polymannuronic acid, polymannuronate, hyaluronic acid, chitosan, chitin, cellulose, starch, glycogen, guar gum, locust bean gum, dextran, levan, inulin, cyclodextrin, agarose, xanthan gum, carageenan, heparin, pectin, gellan gum, and scleroglucan.
Claim 7
Dependent Claim
10 words
The microcapsules of claim 5, wherein said polysaccharide is sulfonated.
Claim 8
Dependent Claim
58 words
The microcapsules of claim 4, wherein A is a polycation selected from the group consisting of polyhistidine, polylysine, polyornithine, polyarginine, polyalanine-polylysine, poly(histidine, glutamic acid)-polyalanine-polylysine, poly(phenylalanine, glutamic acid)-polyalanine-polylysine, poly(tyrosine, glutamic acid)-polyalanine-polylysine, collagen, gelatin; random copolymers of: arginine with tryptophan, tyrosine, or serine; glutamic acid with lysine; glutamic acid with lysine, ornithine; and mixtures of any two or more thereof.
Claim 9
Dependent Claim
23 words
The microcapsules of claim 4, wherein A is a lipid selected from the group consisting of phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol and dilaurylphosphatidic acid.
Claim 10
Dependent Claim
15 words
The microcapsules of claim 4, wherein said modified biocompatible material is ionically and covalently crosslinked.
Claim 11
Dependent Claim
49 words
The microcapsules of claim 1, wherein A is a polysaccharide selected from the group consisting of alginate, high M-content alginate, polymannuronic acid, polymannuronate, hyaluronic acid, chitosan, chitin, cellulose, starch, glycogen, guar gum, locust bean gum, dextran, levan, inulin, cyclodextrin, agarose, xanthan gum, carageenan, heparin, pectin, gellan gum, and scleroglucan.
Claim 12
Dependent Claim
10 words
The microcapsules of claim 10, wherein said polysaccharide is sulfonated.
Claim 13
Dependent Claim
58 words
The microcapsules of claim 1, wherein A is a polycation selected from the group consisting of polyhistidine, polylysine, polyornithine, polyarginine, polyalanine-polylysine, poly(histidine, glutamic acid)-polyalanine-polylysine, poly(phenylalanine, glutamic acid)-polyalanine-polylysine, poly(tyrosine, glutamic acid)-polyalanine-polylysine, collagen, gelatin; random copolymers of: arginine with tryptophan, tyrosine, or serine; glutamic acid with lysine; glutamic acid with lysine, ornithine; and mixtures of any two or more thereof.
Claim 14
Dependent Claim
23 words
The microcapsules of claim 1, wherein A is a lipid selected from the group consisting of phosphatidylethanolamine, phsphatidylserine, phosphatidylinositol, phosphatidylglycerol and dilaurylphosphatidic acid.
Claim 15
Dependent Claim
15 words
The microcapsules of claim 1, wherein said modified biocompatible material is ionically and covalently crosslinked.
Claim 16
Dependent Claim
32 words
The microcapsules of claim 1, wherein said modified biocompatible material is produced by chemically modifying a biocompatible material having a reactive functionality thereon with a reactive species capable of free radical polymerization.
Claim 17
Dependent Claim
22 words
The microcapsules of claim 15, wherein said reactive functionality is a hydroxyl, carboxyl, primary or secondary amine, aldehyde, ketone or ester group.
Claim 18
Dependent Claim
28 words
The microcapsules of claim 15, wherein said reactive species is an alkenoic acid or the corresponding acid chloride or acid anhydride, alkenol, alkenyl halide or organometallic alkenyl compound.
Claim 19
Dependent Claim
14 words
The microcapsules of claim 17, wherein said reactive species is an alkenoic acid anhydride.
Claim 20
Dependent Claim
31 words
The microcapsules of claim 15, wherein said reactive species is an acryloyl chloride, methacryloyl chloride, acrylic acid, methacrylic acid, acrylic anhydride, methacrylic anhydride, allyl alcohol, allyl chloride, or vinyl magnesium bromide.
Claim 21
Dependent Claim
10 words
A drug delivery system comprising the microcapsules of claim 1.
Claim 22
Independent Claim
176 words
A method of making a microcapsule containing biologically active material encapsulated therein, said method comprising: a) suspending said biologically active material in aqueous media that is free of organic solvents, along with a mixture of a modified biocompatible polymerizable material capable of undergoing free radical polymerization and a free radical initiating system, wherein said modified biocompatible material has the formula: A--X wherein: A is selected from the group consisting of polysaccharides, polycations and lipids, and X is a moiety containing a carbon-carbon double bond or triple bond capable of free radical polymerization; and A and X are linked covalently through linkages selected from the group consisting of ester, ether, thioether, disulfide, amide, secondary amines, tertiary amines, direct C--C linkages, sulfate esters, sulfonate esters, phosphate esters, urethanes, and carbonates; b) forming discrete particles comprising said biologically active material surrounded by the modified biocompatible polymerizable material, wherein the largest physical dimension of said discrete particles, including the biologically active material, does not exceed 1 mm; and c) subjecting the modified biocompatible polymerizable material to free radical generating conditions.
Claim 23
Independent Claim
176 words
A method of making a microcapsule containing biologically active material encapsulated therein, said method comprising: a) suspending said biologically active material in aqueous media that is free of organic solvents, along with a mixture of a modified biocompatible polymerizable material capable of undergoing free radical polymerization and a free radical initiating system, wherein said modified biocompatible material has the formula: A--X wherein: A is selected from the group consisting of polysaccharides, polycations and lipids, and X is a moiety containing a carbon-carbon double bond or triple bond capable of free radical polymerization; and A and X are linked covalently through linkages selected from the group consisting of ester, ether, thioether, disulfide, amide, secondary amines, tertiary amines, direct C--C linkages, sulfate esters, sulfonate esters, phosphate esters, urethanes, and carbonates; b) forming discrete particles comprising said biologically active material surrounded by the modified biocompatible polymerizable material, wherein the largest physical dimension of said discrete particles, including the biologically active material, does not exceed 1 mm; and c) subjecting the modified biocompatible polymerizable material to free radical generating conditions.
Claim 24
Dependent Claim
15 words
The method according to claim 21, further comprising adding a comonomer in the suspending step.
Claim 25
Dependent Claim
19 words
The method according to claim 21, wherein said free radical initiating system comprises a photosensitizing agent and a cocatalyst.
Claim 26
Dependent Claim
37 words
The method according to claim 23, wherein said photosensitizing agent is a dye selected from ethyl eosin, eosin, erythrosin, riboflavin, fluoroscein, rose bengal, methylene blue, or thionine; and said cocatalyst is triethanolamine, arginine, methyldiethanol amine, or triethylamine.
Claim 27
Dependent Claim
15 words
The method according to claim 23, wherein said mixture further comprises at least one comonomer.
Claim 28
Dependent Claim
63 words
The method according to claim 25, wherein said comonomer is selected from vinyl pyrrolidinone, acrylamide, methacrylamide, acrylic acid, methacrylic acid, sodium acrylate, sodium methacrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate (HEMA), ethylene glycol diacrylate, ethylene glycol dimethacrylate, pentaerythritol triacrylate, pentaerythritol trimethacrylate, trimethylol propane triacrylate, trimethylol propane trimethacrylate, tripropylene glycol diacrylate, tripropylene glycol dimethacrylate, glyceryl acrylate, glyceryl methacrylate, or combinations of any two or more thereof.
Claim 29
Dependent Claim
102 words
The method according to claim 21, wherein said modified biocompatible polymerizable material is further covalently linked thereto Y, wherein Y is selected from alkylene glycols, polyalkylene glycols, or hydrophobic onium cations, wherein said modified biocompatible material has the formula Y--A--X wherein the linkage between Y and A is selected from the covalent linkages ester, ether, thioether, disulfide, amide, secondary amines, tertiary amines, direct C--C linkages, sulfate esters, sulfonate esters, phosphate esters, urethanes, or carbonates; or the ionic linkage ##STR10## wherein Q is nitrogen or phosphorus, and R is hydrogen, an alkyl radical, an aryl radical, an alkaryl radical, or an aralkyl radical.
Claim 30
Dependent Claim
18 words
The method according to claim 21, further comprising subjecting said modified biocompatible polymerizable material to ionic crosslinking conditions.
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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) | 2001-01-05 | 2001-07-07 | 2002-01-06 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-01-05 | 2005-07-07 | 2006-01-06 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-01-05 | 2009-07-07 | 2010-01-06 | $7700.00 | Window Closed / Lapsed |