Patent US4352883A successfully refreshed from Google Patents.
US4352883A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Encapsulation of biological material
Assignee: Abbott Biotech Inc
•
Filing: 1979-03-28
•
Granted: 1982-10-05
•
Expires: 1999-03-28
Abstract
Abstract A core material such as living tissue, individual cells, hormones, enzymes or antibodies is encapsulated in a semipermeable membrane that is permeable to small molecules for contact with the core material but is impermeable to potentially deleterious large molecules. Encapsulation may be carried out by suspending the core material in an aqueous medium containing a water soluble gum that can be reversibly gelled, forming the suspension into droplets, contacting the droplets with a solution of multivalent cations to gel the droplets as discrete, shape-retaining, water insoluble temporary capsules and cross-linking a surface layer of the temporary capsules to produce a semipermeable membrane around the capsules. Optionally the gel within the membrane may be reliquified by removing multivalent cations from the gel.
Inventors
- 👤 Franklin Lim
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-22 23:28
CPC Classifications
C; C12; C12N; C12N11/00; C12N11/02; C12N11/04; A; A01; A01N; A01N1/00; A01N1/10; A01N1/12; A01N1/128; A61; A61F; A61F2/00; A61F2/02; A61F2/022; A61K; A61K35/00; A61K35/12; A61K35/37; A61K35/39; A61K39/00; A61K39/395; A61K39/44; A61K9/00; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1652; A61K9/48; A61K9/50; A61K9/5005; A61K9/5021; A61K9/5031; A61K9/5036; A61K9/5073; A61L; A61L27/00; A61L27/14; A61L27/20; A61L27/36; B; B01; B01J; B01J13/00; B01J13/02; B01J13/04; B01J13/06; B01J13/08; B01J13/14; B01J13/16; C12M; C12M25/00; C12M25/16; C12N5/00; C12N5/0012; C12N5/06; C12N5/0602; C12N5/067; C12N5/0671; C12N5/0676; C12N5/0677; A61K2035/126; A61K2035/128; A61K38/00; C12N2533/00; C12N2533/30; C12N2533/32; C12N2533/70; C12N2533/74
Claims Analysis
Total Claims: 25
Claim 1
Independent Claim
101 words
A process for encapsulating viable tissue within a semipermeable membrane, said process comprising the steps of: A. suspending finely divided living tissue in an aqueous medium which is physiologically compatible with the tissue and which contains a water soluble substance which (a) is physiologically compatible with the tissue; and (b) can be reversibly gelled to form a coherent, shape-retaining mass; B. forming the suspension into droplets of a size sufficient to envelop tissue; C. gelling the droplets to form discrete, shape-retaining temporary capsules; D. forming a permanent semipermeable membrane about the temporary capsules; and E. reliquifying the gel within the membrane.
Claim 2
Dependent Claim
101 words
A process for encapsulating viable tissue within a semipermeable membrane, said process comprising the steps of: A. suspending finely divided living tissue in an aqueous medium which is physiologically compatible with the tissue and which contains a water soluble substance which (a) is physiologically compatible with the tissue; and (b) can be reversibly gelled to form a coherent, shape-retaining mass; B. forming the suspension into droplets of a size sufficient to envelop tissue; C. gelling the droplets to form discrete, shape-retaining temporary capsules; D. forming a permanent semipermeable membrane about the temporary capsules; and E. reliquifying the gel within the membrane.
Claim 3
Dependent Claim
65 words
A process for encapsulating a core material within a semipermeable membrane, said process comprising the steps of: A. placing the material in a solution of a water-soluble substance that can be reversibly gelled; B. forming the solution into droplets; C. gelling the droplets to produce discrete shape-retaining temporary capsules; D. forming semipermeable membranes about the temporary capsules; and E. reliquifying the gel within said membranes.
Claim 4
Dependent Claim
65 words
A process for encapsulating a core material within a semipermeable membrane, said process comprising the steps of: A. placing the material in a solution of a water-soluble substance that can be reversibly gelled; B. forming the solution into droplets; C. gelling the droplets to produce discrete shape-retaining temporary capsules; D. forming semipermeable membranes about the temporary capsules; and E. reliquifying the gel within said membranes.
Claim 5
Dependent Claim
11 words
The process of claim 2 wherein said substance comprises a gum.
Claim 6
Dependent Claim
60 words
The process of claim 3 wherein said gum has free acid groups and said membrane formation step is effected by contacting the temporary capsules with a polymer of a molecular weight between 3000 and 100,000 daltons and having free amino groups, said contacting being effective to form permanent polymer crosslinks between acid groups in a surface layer of the capsule.
Claim 7
Dependent Claim
32 words
The process of claim 4 wherein the polymer used for crosslinking is selected from the group consisting of polylysine and polyethylenimine, said polymer having an average molecular weight of about 35,000 daltons.
Claim 8
Dependent Claim
32 words
The process of claim 2 wherein the membrane is formed by an interfacial polymerization wherein the temporary capsules are used as a core material in the aqueous phase of a water-in-oil emulsion.
Claim 9
Dependent Claim
36 words
The process of claim 6 wherein the reactants used in the polymerizatiion are selected from the group consisting of water soluble polyols, diols, polyamines, and diamines, and water immiscible diacid halides, diacids, and multifunctional sulfonyl halides.
Claim 10
Dependent Claim
13 words
The process of claim 6 wherein the interfacial polymerization is a polyaddition reaction.
Claim 11
Dependent Claim
23 words
The process of claim 2 wherein the material is selected from the group consisting of enzymes, immunoproteins, activated charcoal particles, and viable tissue.
Claim 12
Dependent Claim
13 words
The process of claim 3 wherein the gum is an alkali metal alginate.
Claim 13
Dependent Claim
15 words
The process of claim 3 wherein the gum comprises a polysaccharide containing free acid groups.
Claim 14
Dependent Claim
20 words
The process of claim 2 wherein said core material is selected from the group consisting of hormones, enzymes and antibodies.
Claim 15
Dependent Claim
120 words
A process for encapsulating a core material within a membrane permeable to proteins of a molecular weight no greater than about 100 thousand daltons, said process comprising the steps of: A. suspending the core material in an aqueous medium which contains a water-soluble gum containing acid groups; B. forming the suspension into droplets; C. subjecting the droplets to a solution of multivalent, cations to gel the droplets as discrete, shape-retaining, water insoluble temporary capsules; and D. permanently cross-linking surface layers of said temporary capsules to produce a semipermeable membrane about said droplets by subjecting them to a polymer containing substitutents reactive with the acid groups of said gum, said polymer having a molecular weight within the range of 3000-100,000 daltons.
Claim 16
Dependent Claim
120 words
A process for encapsulating a core material within a membrane permeable to proteins of a molecular weight no greater than about 100 thousand daltons, said process comprising the steps of: A. suspending the core material in an aqueous medium which contains a water-soluble gum containing acid groups; B. forming the suspension into droplets; C. subjecting the droplets to a solution of multivalent, cations to gel the droplets as discrete, shape-retaining, water insoluble temporary capsules; and D. permanently cross-linking surface layers of said temporary capsules to produce a semipermeable membrane about said droplets by subjecting them to a polymer containing substitutents reactive with the acid groups of said gum, said polymer having a molecular weight within the range of 3000-100,000 daltons.
Claim 17
Dependent Claim
16 words
The process of claim 13 comprising the additional step of resolubilizing the gel within said capsules.
Claim 18
Dependent Claim
21 words
The process of claim 13 wherein the water soluble gum is sodium alginate and multivalent cation solution is a calcium solution.
Claim 19
Dependent Claim
30 words
The process of claim 15 including the additional step of removing the calcium ions contained within said capsules to resolubilize the gelled alginate interior of the membranes of said capsules.
Claim 20
Dependent Claim
36 words
The process of claim 15 wherein said core material is a mammalian tissue selected from the group consisting of Islets of Langerhans, liver, and individual cells thereof and said medium is a physiologically compatible tissue medium.
Claim 21
Dependent Claim
36 words
The process of claim 13 wherein said core material is a mammalian tissue selected from the group consisting of Islets of Langerhans, liver, and individual cells thereof and said medium is a physiologically compatible tissue medium.
Claim 22
Dependent Claim
29 words
The process of claim 13 wherein said core material comprises living tissue and said aqueous medium is a complete tissue culture medium sufficient to maintain said tissue in vitro.
Claim 23
Dependent Claim
20 words
The process of claim 13 wherein said cross-linking polymer is selected from the group consisting of polylysine and and polyethylenimine.
Claim 24
Dependent Claim
17 words
The process of claim 20 wherein the average molecular weight of said polymer is about 35,000 daltons.
Claim 25
Dependent Claim
44 words
The process of claim 13 wherein said forming step is effected by forcing droplets of the suspension through a capillary tube while vibrating the tube within the center of a vortex formed by imparting circular fluid motion to an aqueous solution containing multi-valent cations.
References Cited (Backward Citations)
FR1600988A
Cited
US3522346A
Cited
US3827565A
Cited
US3733205A
Cited
US3725113A
Cited
US3730841A
Cited
US3860490A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1985-10-04 | 1986-04-05 | 1986-10-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1989-10-04 | 1990-04-05 | 1990-10-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1993-10-04 | 1994-04-05 | 1994-10-05 | $7700.00 | Window Closed / Lapsed |