Implantable and refillable biohybrid artificial pancreas
First Claim
1. A refillable biohybrid artificial pancreas comprising an extravascularly implantable semi-permeable biocompatible membrane pouch having port means connected to subcutaneous access means said pouch having an internal reservoir accessible through said port means said reservoir containing an alternative to encapsulation of each pancreatic islet including a thermosensitive polymeric matrix having entrapped therein pancreatic islets said thermosensitive polymer having an LCST of between about 0°
- and 40°
C. and said semi-permeable membrane having a molecular cutoff of between about 10,000 and 100,000 daltons so as to allow passage of insulin from said pouch and promote metabolic functioning of the islets by allowing, nutrients, ions, oxygen and other materials below the molecular cutoff to enter into the pouch while, at the same time, prohibit bacteria, lymphocytes, and large proteins from entering into the pouch.
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0 Petitions
Accused Products
Abstract
An artificial pancreas system which minimizes the volume of the artificial pancreas by not encapsulating each islet is taught wherein the islets are separated and held within a polymeric matrix which is soluble in an aqueous solution below body temperature but insoluble in aqueous solutions at or above body temperature. The polymer-islet mixture is contained in a pouch having access means such as entry and exit ports. The solubility makes it possible to replace the contents of the pouch by solubilizing the matrix simply by lowering the temperature below the LCST. The pouch is constructed of a biocompatible material permeable to insulin and other substances of similar or lesser molecular weight but is impermeable to cellular and humoral components of the body immune system. The islet-polymer matrix can be functionalized to stimulate insulin secretion from the islets using insulinotropic agents such as sulfonylurea. Also, polymeric microparticles which release bioactive agents which either promote vascularization at the pouch membrane outer surface or inhibit macrophage activity can be added to the polymer matrix.
90 Citations
29 Claims
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1. A refillable biohybrid artificial pancreas comprising an extravascularly implantable semi-permeable biocompatible membrane pouch having port means connected to subcutaneous access means said pouch having an internal reservoir accessible through said port means said reservoir containing an alternative to encapsulation of each pancreatic islet including a thermosensitive polymeric matrix having entrapped therein pancreatic islets said thermosensitive polymer having an LCST of between about 0°
- and 40°
C. and said semi-permeable membrane having a molecular cutoff of between about 10,000 and 100,000 daltons so as to allow passage of insulin from said pouch and promote metabolic functioning of the islets by allowing, nutrients, ions, oxygen and other materials below the molecular cutoff to enter into the pouch while, at the same time, prohibit bacteria, lymphocytes, and large proteins from entering into the pouch. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19)
- and 40°
-
20. A method comprising:
- recharging an artificial pancreas comprising an extravascularly implantable semi-permeable biocompatible membrane pouch having port means connected to subcutaneous access means said pouch having an internal reservoir accessible through said port means said reservoir containing an alternative to encapsulation of each pancreatic islet including a thermosensitive polymeric matrix having entrapped therein pancreatic islets said thermosensitive polymer having an LCST of between about 0° and
40°
C. and said semi-permeable membrane having a molecular cutoff of between about 10,000 and 100,000 daltons by the steps of;(a) lowering the temperature of said resident polymeric matrix in said reservoir to the point that said resident matrix changes phases from a solid to a liquid, (b) withdrawing from said reservoir, via said port means of said pouch and said subcutaneous access means, said resident polymeric matrix which has been phase changed from solid to liquid, (c) injecting into said reservoir, via said port means of said pouch and said subcutaneous access means, a fresh liquid phase of thermosensitive polymeric matrix having entrapped therein islets maintained below the LCST of said thermosensitive polymer matrix; and (d) raising the temperature of the polymeric matrix injected into said reservoir above the LCST causing said polymeric matrix to solidify. - View Dependent Claims (21, 22, 23, 24, 25, 26, 27, 28, 29)
- recharging an artificial pancreas comprising an extravascularly implantable semi-permeable biocompatible membrane pouch having port means connected to subcutaneous access means said pouch having an internal reservoir accessible through said port means said reservoir containing an alternative to encapsulation of each pancreatic islet including a thermosensitive polymeric matrix having entrapped therein pancreatic islets said thermosensitive polymer having an LCST of between about 0° and
Specification