Chemistry: molecular biology and microbiology – Carrier-bound or immobilized enzyme or microbial cell;... – Enzyme or microbial cell is immobilized on or in an organic...
Reexamination Certificate
1999-11-02
2002-06-04
Weber, Jon P. (Department: 1651)
Chemistry: molecular biology and microbiology
Carrier-bound or immobilized enzyme or microbial cell;...
Enzyme or microbial cell is immobilized on or in an organic...
C435S177000, C435S382000, C424S424000
Reexamination Certificate
active
06399341
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates in general to artificial organs and more specifically to an artificial pancreas device comprising agar microbeads.
The prior art while replete with encapsulation techniques is still devoid of an encapsulation technique which mimicks the function of the in vivo organ intended to be replaced. Thus in the case of insulin delivery, the existing encapsulation techniques employ pancreatic islet cells encapsulated in an alginate semipermeable membrane. The drawback of such techniques is as follows.
First, alginate gels by an ionic mechanism. The polymer-reacts with di- or trivalent cations in such a way that the polymer structure becomes ionically cross-linked and forms a gel structure. The gels thus formed are thermally stable, but because of their ionic nature can be destabilized by substances which sequester the cross-linking ions.
Second, alginate beads are usually further processed by coating with poly-L lysine to produce a semi-permeable shell around the alginate itself for immunoisolation of the encapsulated material. In most cases the alginate core is then dissolved so that the alginate beads actually end up as poly-L-lysine capsules. The use of poly-L-lysine has been shown, however, to cause severe aggregation and clumping of the beads which cause the cells to stop functioning. Moreover, poly-L-lysine is itself reactive leading to immunological rejection and bioincompatibiliy which results in host rejection and fibrotic overgrowth and unwanted bead aggregation leading to decreased cell function.
Third alginate beads are potentially dissolvable in environments which contain substances which sequester calcium or barium.
Fourth, alginate beads have been reported to elicit unwanted biological responses, most notably cytokine release and fibrotic growth. Notably, there is an ongoing debate whether these responses are caused by the alginate itself, the particular type of alginate, the coating poly-L-lysine as noted above or some other factor.
Fifth, the long term stability of alginate beads aside from the aforementioned problems, has been called into question.
Lastly, implanted alginate beads are not retrievable once they stop functioning or start leading to adverse clinical effects.
Therefore, a need still exists for a method to encapsulate viable pancreatic cells which allows for the production of insulin while guarding against the host's immune system.
SUMMARY OF THE INVENTION
The aforementioned need is met in an elegant and novel manner by providing for an artificial pancreas comprising one or more viable and physiologically active pancreatic islet cells capable of producing insulin, encapsulated within a semipermeable spheroidal membrane comprising agar gel. Said artificial pancreas may be installed within a diffusion chamber or perfusion chamber containing a hollow fiber.
The present invention further provides for an encapsulation process comprising the steps of suspending islet cells in molten agar and emulsifying said solution in a hydrophobic phase to form an emulsion of small liquid droplets suspended in hydrophobic phase. Cooling of the oil thereafter causes the droplets to gel resulting in the formation of agar gel microbeads.
Lastly the present invention provides for a tissue implantation method comprising the aforementioned encapsulation steps followed by introducing said encapsulated beads into a mammalian body.
REFERENCES:
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patent: 5053332 (1991-10-01), Cook et al.
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patent: 5531997 (1996-07-01), Cochrum
patent: 5643569 (1997-07-01), Jain et al.
Sun, A.M., Microencapsulation of pancreatic islet cells: A bioartificial endocrine pancreas (1988) Methods of Enzymology, vol. 137, pp. 575-580.*
Iwata et al., Agarose for a bioartificial pancreas (1992) Journal of Biomedical Materials Research, vol. 26, pp. 967-977.
Mullon Claudy Jean Paul
O'Neil John Joseph
Stegemann Jan Philip
Guttman Harry J
Law Offices of Margit Maus and Associates
Weber Jon P.
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