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EP0127989A2
Expired / Lapsed
EP
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Microencapsulation of living tissue and cells
Assignee: Sanofi Pasteur Ltd
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Filing: 1984-05-25
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Granted: —
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Expires: 2004-05-25
Abstract
Abstract Living tissue or cells, for example, islets of Langerhans, are microencapsulated for implantation in the body for long term treatment of diabetes or other disease requiring organ transplantation. The microcapsules take the form of a biocompatible semi-permeable hydrogel membrane based on polylysine which permits the passage of materials and oxygen to the cells and metabolic products from the cells while retaining the cells encapsulated. The biocompatible semi-permeable membrane has an outer negatively-charged surface, which, combined with a controlled thickness of polylysine of molecular weight from 10,000 to 30,000 daltons, imparts to the microcapsules the ability to maintain long term effectiveness.
Inventors
- 👤 Mattheus Florentius Albertus Goosen
- 👤 Geraldine Margaret O'shea
- 👤 Anthony Mein-Fang Sun
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 21:54
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/48; A61K9/50; A61K9/5005; A61K9/5021; A61K9/5036; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1652; A61K9/5031; A61K9/5073
Claims Analysis
Total Claims: 25
Claim 1
Independent Claim
171 words
A microcapsule having a diameter of about 500 to about 2000 pm and suitable for implantation into an animal body, characterized by a core comprising one or more viable, healthy, physiologically-active tissue cells capable of ongoing metabolism; and a biocompatible semi-permeable membrane surrounding and enclosing the core, the semi-permeable membrane being permeable to tissue nutrients and metabolic products produced by the tissue but impermeable to immune system proteins, the semi-permeable membrane having a molecular weight cut-off of below about 150,000 daltons; the biocompatible membrane being a hydrogel formed by ionic reaction between a polylysine polymer having a molecular weight from about 10,000 to about 30,000 daltons and a polymeric material bearing negatively-charged groups to provide an outer negatively-charged surface, the polylysine polymer membrane having a durability sufficient to permit the microcapsules to be injected in the animal body and sufficient to maintain the microcapsules in an intact form and to permit the tissue to effect ongoing metabolism when injected into the animal body for a period of time exceeding three months.
Claim 2
Dependent Claim
171 words
A microcapsule having a diameter of about 500 to about 2000 pm and suitable for implantation into an animal body, characterized by a core comprising one or more viable, healthy, physiologically-active tissue cells capable of ongoing metabolism; and a biocompatible semi-permeable membrane surrounding and enclosing the core, the semi-permeable membrane being permeable to tissue nutrients and metabolic products produced by the tissue but impermeable to immune system proteins, the semi-permeable membrane having a molecular weight cut-off of below about 150,000 daltons; the biocompatible membrane being a hydrogel formed by ionic reaction between a polylysine polymer having a molecular weight from about 10,000 to about 30,000 daltons and a polymeric material bearing negatively-charged groups to provide an outer negatively-charged surface, the polylysine polymer membrane having a durability sufficient to permit the microcapsules to be injected in the animal body and sufficient to maintain the microcapsules in an intact form and to permit the tissue to effect ongoing metabolism when injected into the animal body for a period of time exceeding three months.
Claim 3
Dependent Claim
16 words
The microcapsule claimed in claim 1, characterized in that the tissue cells are islets of Langerhans.
Claim 4
Dependent Claim
20 words
The microcapsule claimed in claim 1 or 2, characterized in that the negatively charged groups are carboxyl or hydroxy groups.
Claim 5
Dependent Claim
29 words
The microcapsule claimed in claim 3, characterized in that the polymeric material bearing negatively charged groups is selected from the group consisting of alginate, polyvinyl alcohol or polylactic acid.
Claim 6
Dependent Claim
26 words
The microcapsule claimed in any one of claims 1 to 4, characterized in that the polylysine has a molecular weight of about 15,000 to about 25,000.
Claim 7
Dependent Claim
18 words
The microcapsule claimed in claim 5, characterized in that the polylysine has a molecular weight of about 17,000.
Claim 8
Dependent Claim
35 words
The microcapsule claimed in any one of claims 1 to 6 having a diameter of about 700 to about 1000 um and characterized in that the semi-permeable membrane has a thickness of about 5 µm.
Claim 9
Dependent Claim
25 words
The microcapsule claimed in any one of claims 1 to 7, characterized in that the membrane has a molecular weight cut-off of about 67,000 daltons.
Claim 10
Dependent Claim
34 words
The microcapsule claimed in any one of claims 1 to 8, characterized in that the core also c.omprises an aqueous medium of nutrients sufficient tc maintain the tissue cells and allow normal metabolism thereof.
Claim 11
Independent Claim
199 words
A method of encapsulating a core material within a semi-permeable membrane to form microcapsules for implantation into an animal body, characterized by (a) placing the material in an aqueous solution of a water-soluble polymeric substance that can be reversibly gelled and which has free acid grc-ups; (b) forming the solution into droplets; (c) gelling the droplets to produce discrete shape-retaining temporary capsules; (d) forming semi-permeable membranes about the temporary capsules by contact between the temporary' capsules and a polymer containing fuee amino groups to cause ionic reaction with the acid groups in a surface layer of the capsule, the polymer containing free amino groups being polylysine having a molecular weight of about 10,000 to about 30.000 daltons, the contact being effected for a period of time sufficient to provide a polymer coating on the temporary capsule of sufficient durability to permit the microcapsules to be injected into the animal body; and (e) contacting the microcapsules formed in step (d) with a biocompatible polymeric material which contains free negatively-charged groups capable of ionic reaction with the free amino groups in a surface layer of the microcapsule, thereby to form an outer coating of the biocompatible polymeric material on said microcapsules.
Claim 12
Independent Claim
199 words
A method of encapsulating a core material within a semi-permeable membrane to form microcapsules for implantation into an animal body, characterized by (a) placing the material in an aqueous solution of a water-soluble polymeric substance that can be reversibly gelled and which has free acid grc-ups; (b) forming the solution into droplets; (c) gelling the droplets to produce discrete shape-retaining temporary capsules; (d) forming semi-permeable membranes about the temporary capsules by contact between the temporary' capsules and a polymer containing fuee amino groups to cause ionic reaction with the acid groups in a surface layer of the capsule, the polymer containing free amino groups being polylysine having a molecular weight of about 10,000 to about 30.000 daltons, the contact being effected for a period of time sufficient to provide a polymer coating on the temporary capsule of sufficient durability to permit the microcapsules to be injected into the animal body; and (e) contacting the microcapsules formed in step (d) with a biocompatible polymeric material which contains free negatively-charged groups capable of ionic reaction with the free amino groups in a surface layer of the microcapsule, thereby to form an outer coating of the biocompatible polymeric material on said microcapsules.
Claim 13
Dependent Claim
28 words
The method claimed in claim 10, characterized in that the core material comprises living tissue which is in finely-divided suspended form in the aqueous solution in step (a).
Claim 14
Dependent Claim
37 words
The method claimed in claim 11, characterized in that the living tissue comprises islets of Langerhans whereby the microcapsules may be used to control blood sugar levels in diabetic animal bodies into which the microcapsules are implanted.
Claim 15
Independent Claim
22 words
The method claimed in any one of claims 10 to 12, characterized in that the reve::sibly-gellable water-soluble substance is a polysaccharide gum.
Claim 16
Dependent Claim
16 words
The method claimed in claim 13, characterized in that the gum is an alkali metal alginate.
Claim 17
Dependent Claim
40 words
The method claimed in claim 14, characterized in that the alkali metal alginate is sodium alginate and the viscosity of the aqueous solution of sodium alginate is at least sufficient to result in the formation of substantially spherical temporary capsules.
Claim 18
Dependent Claim
23 words
The method claimed in claim 15, characterized in that the aqueous sodium alginate solution has a viscosity of at least about 30 cps.
Claim 19
Independent Claim
27 words
The method claimed in any one of claims 10 to 16, characterized in that the polylysine has a molecular weight of about 15,000 to about 25,000 daltons.
Claim 20
Independent Claim
37 words
The method claimed in any one of claims 10 to 17, characterized in that the contact in step (d) is effected for a period of time sufficient to provide a polylysine layer of thickness about 5 um.
Claim 21
Independent Claim
35 words
The method claimed in any of claims 10 to 18, characterized in that the contact in step (d) is effected by contact with an aqueous solution of polylysine at about 6 to about 9 minutes.
Claim 22
Dependent Claim
23 words
The method claimed in claim 19, characterized in that the aqueous solution of polylysine has a concentration of at least about 0.05 wt.%.
Claim 23
Independent Claim
35 words
The method claimed in any one of claims 10 to 20, characterized in that the biocompatible negatively-charged polymeric material is a polyvinyl alcohol having free hydroxyl groups or a polylactic acid containing free acid groups.
Claim 24
Independent Claim
29 words
The method claimed in any or.e of claims 10 to 21, characterized in that the reversibly-gellable water-soluble substance comprises sodium alginate and the biocompatible polymeric material comprises sodium alginate.
Claim 25
Independent Claim
24 words
The method claimed in any one of claims 10 to 22, characterized by the further step of reliquifying the gel within the semi-permeable membrane.
References Cited (Backward Citations)
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