Patent US3938096A successfully refreshed from Google Patents.
US5308701A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Ionically cross-linked polymeric microcapsules
Assignee: Individual
•
Filing: 1992-05-08
•
Granted: 1994-05-03
•
Expires: 2012-05-08
Abstract
Abstract A method for encapsulating biologically-labile materials such as proteins, liposomes, bacteria and eucaryotic cells within a synthetic polymeric capsule, and the product thereof, are disclosed. The method is based on the use of a water-soluble polymer with charged side chains that are crosslinked with multivalent ions of the opposite charge to form a gel encapsulating biological material, that is optionally further stabilized by interactions with multivalent polyions of the same charge as those used to form the gel. In the preferred embodiment, hydrolytically stable polyphosphazenes are formed of monomers having carboxylic acid side groups that are crosslinked by divalent or trivalent cations such as Ca 2+ or Al 3+ , then stabilized with a polycation such as poly-L-lysine. A variety of different compositions can be formed from the crosslinked polymer. In a preferred embodiment, microcapsules are made by spraying an aqueous solution of polyphosphazene and material to be encapsulated into a calcium chloride solution. A semi-permeable membrane is formed on the microspheres by complexation of the surface carboxylate groups with poly(L-lysine).
Inventors
- 👤 Smadar Cohen
- 👤 Carmen Bano
- 👤 Karyn B. Visscher
- 👤 Marie B. Chow
- 👤 Harry R. Allcock
- 👤 Robert S. Langer
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 22:37
CPC Classifications
A; A61; A61K; A61K49/00; A61K49/22; A61K49/222; A61K49/223; A61K49/225; A61K49/226; A61K51/00; A61K51/12; A61K51/1258; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1641; A61K9/48; A61K9/50; A61K9/5005; A61K9/5021; A61K9/5031; B; B01; B01J; B01J13/00; B01J13/02; B01J13/06; B01J13/14; C; C08; C08G; C08G79/00; C08G79/02; C08G79/025; C12; C12N; C12N11/00; C12N11/02; C12N11/04; A61K2123/00; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984; Y10T428/2985; Y10T428/2987
Claims Analysis
Total Claims: 16
Claim 1
Independent Claim
225 words
A composition prepared from an ionically crosslinkable synthetic polymer that is soluble in an aqueous solution prior to crosslinking and has charged side groups which are crosslinked by reaction of the side groups with multivalent ions of the opposite charge to form a gel, followed by reaction of the side groups with multivalent polyions of the opposite charge to form a semi-permeable membrane, wherein the polymer is a polyelectrolyte selected from the group consisting of poly(phosphazenes), poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid or methacrylic acid and polyvinyl ethers or poly(vinyl acetate), sulfonated polystyrene, poly(vinyl amines), poly(vinyl pyridine), poly(vinyl imidazole), imino substituted polyphosphazenes, ammonium or quaternary salts and copolymers thereof, is soluble in an aqueous solution selected from the group consisting of water, aqueous alcohol, and buffered aqueous salt solutions and has charged side groups which are crosslinked by reaction of the side groups with multivalent ions of the opposite charge, wherein multivalent cations are selected from the group consisting of calcium, copper, aluminum, magnesium, strontium, barium, tin, organic cations, poly(amino acids), poly(ethyleneimine), poly(vinylamine), poly(allyl amine) and polysaccharides, and multivalent anions are selected from the group consisting of dicarboxylic acids, sulfate ions, carbonate ions, poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid or methacrylic acid, sulfonated poly(styrene) and poly(styrene) with carboxylic acid groups, wherein the gel is insoluble in an aqueous solution after crosslinking.
Claim 2
Dependent Claim
225 words
A composition prepared from an ionically crosslinkable synthetic polymer that is soluble in an aqueous solution prior to crosslinking and has charged side groups which are crosslinked by reaction of the side groups with multivalent ions of the opposite charge to form a gel, followed by reaction of the side groups with multivalent polyions of the opposite charge to form a semi-permeable membrane, wherein the polymer is a polyelectrolyte selected from the group consisting of poly(phosphazenes), poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid or methacrylic acid and polyvinyl ethers or poly(vinyl acetate), sulfonated polystyrene, poly(vinyl amines), poly(vinyl pyridine), poly(vinyl imidazole), imino substituted polyphosphazenes, ammonium or quaternary salts and copolymers thereof, is soluble in an aqueous solution selected from the group consisting of water, aqueous alcohol, and buffered aqueous salt solutions and has charged side groups which are crosslinked by reaction of the side groups with multivalent ions of the opposite charge, wherein multivalent cations are selected from the group consisting of calcium, copper, aluminum, magnesium, strontium, barium, tin, organic cations, poly(amino acids), poly(ethyleneimine), poly(vinylamine), poly(allyl amine) and polysaccharides, and multivalent anions are selected from the group consisting of dicarboxylic acids, sulfate ions, carbonate ions, poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid or methacrylic acid, sulfonated poly(styrene) and poly(styrene) with carboxylic acid groups, wherein the gel is insoluble in an aqueous solution after crosslinking.
Claim 3
Dependent Claim
15 words
The composition of claim 1 wherein the gel is in the form of a microsphere.
Claim 4
Dependent Claim
26 words
The composition of claim 1 wherein the semi-permeable membrane forms a microcapsule and the gel is liquified within the microcapsule by removal of the multivalent ions.
Claim 5
Dependent Claim
16 words
The composition of claim 1 wherein the side groups are acidic and the ions are cations.
Claim 6
Dependent Claim
16 words
The composition of claim 1 wherein the side groups are basic and the ions are anions.
Claim 7
Independent Claim
219 words
A method for synthesizing a synthetic polymeric crosslinked material comprising: reacting an ionically crosslinkable synthetic polymer that is soluble in an aqueous solution and has charged side groups with a multivalent ion to form a gel, and then complexing the charged groups on the surface of the gel with a multivalent polyion to form a semi-permeable membrane, wherein the polymer is a polyelectrolyte selected from the group consisting of poly(phosphazenes), poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid or methacrylic acid and polyvinyl ethers or poly(vinyl acetate), sulfonated polystyrene, poly(vinyl amines), poly(vinyl pyridine), poly(vinyl imidazole), imino substituted polyphosphazenes, ammonium or quaternary salts and copolymers thereof, is soluble in an aqueous solution selected from the group consisting of water, aqueous alcohol, and buffered aqueous salt solutions and has charged side groups which are crosslinked by reaction of the side groups with multivalent ions of the opposite charge, wherein multivalent cations are selected from the group consisting of calcium, copper, aluminum, magnesium, strontium, barium, tin, organic cations, poly(amino acids), poly(ethyleneimine), poly(vinylamine), poly(allyl amine) and polysaccharides, and multivalent anions are selected from the group consisting of dicarboxylic acids, sulfate ions, carbonate ions, poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid or methacrylic acid, sulfonated poly(styrene) and poly(styrene) with carboxylic acid groups, wherein the gel is insoluble in an aqueous solution after crosslinking.
Claim 8
Independent Claim
219 words
A method for synthesizing a synthetic polymeric crosslinked material comprising: reacting an ionically crosslinkable synthetic polymer that is soluble in an aqueous solution and has charged side groups with a multivalent ion to form a gel, and then complexing the charged groups on the surface of the gel with a multivalent polyion to form a semi-permeable membrane, wherein the polymer is a polyelectrolyte selected from the group consisting of poly(phosphazenes), poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid or methacrylic acid and polyvinyl ethers or poly(vinyl acetate), sulfonated polystyrene, poly(vinyl amines), poly(vinyl pyridine), poly(vinyl imidazole), imino substituted polyphosphazenes, ammonium or quaternary salts and copolymers thereof, is soluble in an aqueous solution selected from the group consisting of water, aqueous alcohol, and buffered aqueous salt solutions and has charged side groups which are crosslinked by reaction of the side groups with multivalent ions of the opposite charge, wherein multivalent cations are selected from the group consisting of calcium, copper, aluminum, magnesium, strontium, barium, tin, organic cations, poly(amino acids), poly(ethyleneimine), poly(vinylamine), poly(allyl amine) and polysaccharides, and multivalent anions are selected from the group consisting of dicarboxylic acids, sulfate ions, carbonate ions, poly(acrylic acids), poly(methacrylic acids), copolymers of acrylic acid or methacrylic acid, sulfonated poly(styrene) and poly(styrene) with carboxylic acid groups, wherein the gel is insoluble in an aqueous solution after crosslinking.
Claim 9
Dependent Claim
17 words
The method of claim 6 wherein the charged side groups are acidic and the ions are cations.
Claim 10
Dependent Claim
34 words
The method of claim 7, wherein the acidic side chains contain moieties selected from the group consisting of carboxylic acid groups, sulfonic acid groups, halogenated alcohol groups, phenolic OH groups, and acidic OH groups.
Claim 11
Dependent Claim
44 words
The method of claim 7 wherein the composition is prepared by reacting a polyphosphazene having acidic side groups with a multivalent cation to form a gel, and then complexing the acidic groups on the surface with a multivalent polycation to form a semi-permeable membrane.
Claim 12
Dependent Claim
16 words
The method of claim 6 wherein the side groups are basic and the ions are anions.
Claim 13
Dependent Claim
14 words
The method of claim 6, wherein the polymer further comprises a hydrolyzable side group.
Claim 14
Dependent Claim
26 words
The method of claim 7 wherein the hydrolyzable side group contains a moiety selected from the group consisting of imidazole, amino acid ester, glycerol, and glucosyl.
Claim 15
Dependent Claim
16 words
The method of claim 6 further comprising forming the gel in the shape of a microsphere.
Claim 16
Dependent Claim
20 words
The method of claim 1 further comprising liquefying the gel after formation of the semi-permeable membrane to form a microcapsule.
References Cited (Backward Citations)
US4352883A
Cited
US4765973A
Cited
US4908233A
Cited
US4880622A
Cited
US5089272A
Cited
US5132117A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1997-05-02 | 1997-11-01 | 1998-05-03 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-05-02 | 2001-11-01 | 2002-05-03 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-05-02 | 2005-11-01 | 2006-05-03 | $7700.00 | Window Closed / Lapsed |