Title of Invention	THE GRAFT COPOLYMER FOR THE ENCAPSULATION AND IMMUNOISOLATION OF LIVING CELLS
Abstract	The invention relates to the graft copolymer for the encapsulation and immunoisolation of living cells, comprising 80 to 90 wt% of a biocompatible polyurethane and 10 to 20 wt% of a biocompatible vinyl polymer.

Full Text

FIELD OF THE INVENTION This invention relates to polymethane graft polymer For the encapsulation and ImmunoIsolation of living cells, and a process for the preparation thereof. BACKGROUND OF THE INVENTION Type I diabetes, an autoimmune disorder of endocrine pancreas is a major health concern worldwide and has long term systemic complications. Transplantation of isolated insulin secreting islet cells can be considered as an alternate treatment for diabetes. Immunorejectlon of the islet cells is a major concern of such transplant procedures. Critical shortage of donor islet cells Is another concern of such technology. It is hence desirable to immunoisolate or encapsulate islet cells In semipermeable membranes and form bio hybrid pancreatic devices. The membrances of the device are expected to permit the crossover of molecular weight substances such as nutrient electrolytes, oxygen and biosecretor products but not of transplant effectors. Polymeric membranes such as alginate-poty (L-fyslrte), polycarbonate, poly-vinyl chloride-acrylic copolymers, poly (2-hydroxy ethyl methacryfate) agarose, polyvinyl alcohol have been proposed as irnmu no Isolation matrices. Such membranes have been used in various device configurations Including microcapsules, AV shunts, hollow fibres end planar diffusion chambers. However, flbrotic reactions, blocompatiblitty, mechanical fragility and reduced permeation have been reported to be the limiting factors for the widespread use of these candidate materials. It is the basic requirement that the membrane materials should exhibit satisfactory blocompatibility, i.e. the ability of the material to allow the cells to retain their viability in contact with the materials. The function of the membrane material is also not expected to alter when in contact with the cells. It should also be possible to retrieve the material after use without degradation for a successful application of this technology as the degraded membranes may pose problems In the long term by Inducing antigenic reactions. OBJECTS OF THE INVENTION It is therefore an object of this Invention to propose a graft polymer which does not induce fibrotic reactions. It Is a further object of this invention to propose a graft polymer which is biocompatible. Another object of this Invention is to propose a graft polymer which is effective for the treatment of diabetes without immunosuppression. Yet another object of this invention is to propose a graft polymer for ImmunoIsolating and encapsulating cells within the membrane and which permit the cells to be viable. Other objects and advantages of this Invention will be apparent from the ensuing description. BRIEF DESCRIPTION Thus according to this invention is provided a polyurethane graft polymer for the encapsulation and immunoisolation of living cells. in accordance with this invention, the polymeric material has a composition which is mostly 80-90 wt% of a biocompatible polyurethane and 10-20 wt% of a biocompatible vinyl polymer. The polymeric composition is a graft copolymer whore the first polymer is a polyurethane and tne second or consecutive polymers are hydrophobic and hydrophilic vinyl polymers. The vinyl polymers are •elected from polyvinyl pyrroHdone, polyhydroxyethyl methacrylate, polyethylhexyl acrylate. The polyurethane Is a linear segmented polyurethane which has hard and soft segments and may be aromatic or aliphatic in nature. The soft segment Is, for eg. a polyol. The hard segment is formed by reacting a diol or diamine with an Isocyanate. According to this invention is further provided a process for the preparation of polyurethane graft copolymers. In accordance with this invention is further provided a process for the preparation of the graft copolymer which comprises in a first step of forming the polyurethane by reacting an isocyanate with a polyol In stoichiometric amounts to form a prepolymer of a polyurethane and further extension of the prepolymer by reacting with a stoichiometric amount of diol chain extender and curing. The polyurethane is first formed into a flat sheet or tube or other configuration and further grafted with a vinyl polymer by radiation grafting technique. The step of grafting is carried out by allowing the polyurethane to swell in a mixture of vinylmonomer, initiator and cross-linker for fixed lime periods followed by polymerisation. The grafted polyurethane Is extensively cleaned with distilled water, and organic solvents to remove unreacted components and render the materials biocompatible. Preparation of polyurethane 1-2 molar toluene dissocyanate (TDI) solution is taken on a polymer reactor fitted with water condensor, si If re, and nitrogen purge 0.10 to 0.50 molar polyol which may be either polytetram ethylene glycol or polypropylene glycol dissolved in solvent dimethyl for mamide is added slowly to the TDI solution with continuous stirring and nitrogen gas purge. A catalyst dlbutyl tin dllaurate of 0.01 wt% Is added and temperature raised to 60-70°0 for one to two hours. Chain extension is carried out by bringing down the temperature to 40°C and addition of 0.70 to 0.80 moles of 1, 4-butandlol. Temperature was once again raised to 60-70°C for 48 hours curing In polyethylene molds. After curing, the potyurethanes were subjected to extraction by water before further characterisation. Concentration of TOI, polyol and chain extender may be varied from 0-101 in each case to prepare different hard segments In the pofyurethane. Preparation of graft copolymer A pofyurethane potymer with 10 to 40% hard segments was used for grafting purposes. Pofyurethane was allowed to swell in vinyl monomers such as hydro xyethy Mm ethacry late N-vinyl pyrrolldone and ethyl hexyl a cry late, ethyline glycol dimeth acrylate or any other vinyl crosslinker. A crosslinker of 1-3 wt% of vinyl monomer concentration was added to the vinyl monomer 0.005 u Cu+ was also added. Swollen polymer samples were lightly pressed between filter paper to remove adhered monomer and immediately subjected to gamma irradiation from Co50 source, under a blanket of nitrogen. Dose rates of 0.25- u rad was used for grafting and grafting yields of 5 to 25% were obtained. Grafted potyurethanes were extracted with distilled water and methanol for removing any unreacted monomers. The membranes thus obtained are selectively permeable to cell nutrients, metabolites and waste molecules that are having molecular weights of less than 60,000 and Impermeable to the higher molecular weight components of the physiologic system including immunoglobulins. Further, the membranes are biocompatible to living cells that include islet cells but are not restricted to islet cells only. The Invention Is also not restricted to the permeation of molecules of lesser molecular weight than 60,000 that are relevant for the treatment of diabetes, but to the treatment of any other disease, that requires such selective permeation characteristics for Immunolsolatlon of living cells. The invention will now be explained in greater details with the help of the following non-limiting examples. Example 1.05 molar TDI was taken In polymer reactor. 0.25 M of porytetrametrtylene glycol was added with 0.01 wt% of dlbutyltlndlla urate. 25 ml of dimethyl formamlde was used as solvent and reaction carried out under nitrogen purge. After heating for 1 hour at 6 0°C temperature was reduced to 40°C and 0 70 moles of 1, 4-butanediol added as chain extender and reacted for 30 minutes. The mixture was then poured into a polyethylene mold and allowed to cure at 48 hours at 60°C before extraction In distilled water. The above polyurethane 32% has a hard segmentation of Polyurethane - graft - ethyl -hexyl acrylate A 32% hard segmented polyurethane was cut In the form of a strip of 10 x 1 x 0.1 cm, weighed and was swollen in Ethyl hexyl acrylate monomer for 20 minutes. The swollen polyurethane film was removed, plotted between filter paper and subjected to gamma irradiation under a blanket of nitrogen in a Co80 panoromic batch irradiator. A dose of 0.5 µrad was given. The material was allowed to polymerise and then extracted with water and methanol and dried and weighed to get the weight of grafted copolymer. WE CLAIM: 1. A graft copolymer for the encapsulation and immunoisolation of living cells. 2. The graft copolymer as claimed in claim 1, comprising 80 to 90 wt% of a biocompatible polymethane and 10 to 20 wt% of a biocompatible vinyl polymer. 3. The graft copolymer as claimed In claim 1, wherein said polymer Is a graft of a first polymer being a poly methane and the second or consecutive polymers being hydrophobic and hydrophilic vinyl polymers. 4. The graft copolymer as claimed In claim 3, wherein said vinyl polymers are selected from polyvinyl pyrrolidone, polyhydroxyethyl methacryiate, pofyethylhexyi acrylate. 5. The graft copolymer as claimed In claim 1, wherein said polyurethane Is a linear segmented polyurethane with hard and soft segments and may be aromatic or aliphatic In nature. 6. The graft copolymer as claimed in claim 5, wherein the soft segment is a poryol and the hard segment is formed by reacting a diol or diamine with an Isocyanate.

Documents:

0848-che-2005-correspondnece-others.pdf

0848-che-2005-description(provisional).pdf

0848-che-2005-form 1.pdf

0848-che-2005-form 3.pdf

848-CHE-2005 ABSTRACT.pdf

848-CHE-2005 CORRESPONDENCE OTHERS.pdf

848-CHE-2005 CORRESPONDENCE PO.pdf

848-CHE-2005 FORM 1.pdf

848-CHE-2005 FORM 18.pdf

848-CHE-2005 PETITON.pdf

848-CHE-2005 POWER OF ATTORNEY.pdf

848-che-2005-claims.pdf

848-che-2005-description(complete).pdf