Title of Invention	A CROSSLINKABLE AND NON-AROMATIC POLYURETHANE POTTING COMPOUND
Abstract	A cross-linkable and non-auomatic polyethar potting compound comprising a blend componed I of iso cyanate terminal prepolymer of polyethane and component II of aliohatic non-auomatic disocyanate wherein componenet I &II is present in the ratio of 20:80 & 80:20 totalling 100.

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This invention relates to a cross 1inkable and non-aromatic polyurethane potting compound. BACKGROUND Cross 1inkable polyurethanes have wider applications in general as well as biomedical applications, such as adhesive and potting compounds. Potting compounds are generally used to encapsulate a component in a module. Such potting compounds are essentially used for encapsulating hollow fibers for fabrication of hollow fiber haemodialyzer for biomedical application. Polyurethanes are generally produced using a diisocyanate, polyol and hardener or chain exten^der. Aromatic polyurethanes based on toluene diisocyanate (TDI) and diphenyl methane dilsocyanate (MDI) are susceptible to degrade if processed in the presence of moisture and if autoclaved in an aqueous solution. In this connection, reference is made to M Szycher, V C Poirier, D J Demsey, J Elasto Plast. 15 (1963) pg. 81 and to A Mazzu, C P Smith, J Biomed. Hat. Res., 18 (1984) pg. 961. Gamma radiation and autoclaving are used to sterilise devices which are fabricated using polyurethane polymers. Excessive and repeated sterilisation are prone to cause chain scission of polyurethane and formation of low molecular weight components. Reference is also made to A Mazzu, C P Smith, J Biomed. Mat. Res. 18 (1984) pg. 961. It has been reported that a potential carcinogenic chemical 4,4'-methy1ene dianiline (MDA) is formed in thermo- plastic MDI based polyurethane during autoclave sterilisation. Reference is made to A Mazzu, C P Smith, J Biomed. Mat. Res., 18 (2) has been found as hydrolytic products of toluene diisocyanate based polyurethane foam (Microthane) when it reacts with water at elevated temperature. Reference is invited to C Batich, J Williams, R King, J Biomed. Mat. Res., 23, (1983), pg. 311. TDA has been detected in clinical samples of urine and breast tissue of patients with 7 months old polyurethane (Polyester-TDI) foam (R) covered covered Meme breast implants (M/s Surgitek >. In this connection, reference is invited to S C Chan, D C Birdsell, C Y Gradeen, Clin. Chem. 37 (1991) pg. 2143. The degradation of (R) (R) Microthane foam cover in Meme breast implant has resulted in court litigation and the implant was withdrawn from the market. PRIOR ART Apart from the risks associated with the use of aromatic poly-urethanes as implants in biomedical applications, aromatic poly¬urethane (MDI based) potting compounds which were used in the fabrication of haemodialyzers were found to leach MDA in serum after gamma irradiation sterilisation with increased dose of radiation. In this connection, reference is invited to HShintani and A Nakamura, J Biomed. Mat. Res., 25 (1991) pg. 1275. Some investigators have reported carcinogenic response of MDA in rodents. In this connection, reference is made to J Autian, A R Singh, J E Turner Cancer. Res., 35 (975) pg. 1591. OBJECTS OF THE INVENTION It is thus an object of this invention to develop a biocompatible cross 1inkable and non-aromatic potting compound for fabrication of hollow fiber haemodialyzer. Another object of this invention is to propose a process for the production of cross 1inkable potting compound with minimum setting time for fabrication of hollow fiber haemodialyzer. Further objects and advantages of this invention will be more apparent from the ensuing description. DESCRIPTION OF THE INVENTION According to this invention, there is provided a cross Iinkable and non-aromatic polyurethane potting compound comprising a blend of component I of isocyanate terminated prepolymer of poly¬urethane and component II of aliphatic, non-aromatic di isocyanate. Reference is hereinafter made to the various steps with the numeral values of the parameters. However, such a reference to the numerical values is only by way of an example and without Intending to imply any limitation on the scope of the invention. Preparation of isocyanate terminated polyurethane prepolymer (component I) is carried out with a difunctional aliphatic diisocyanate compound such as hexamethyIene diisocyanate and dicyclohexyl methane diisocyanate and a polyfunctional polyol which is generally a multifunctional water-inso]uble polyol such o as castor oil, at a temperature of 40-150 C for 10-60 mins. under inert atmosphere. The prepolymer is cooled and stored under cold conditions. The component II is prepared by blending a difunc¬tional hydroxyl terminated polymer of molecular weight ranging 400-3000 with a diester based activator at a temperature of 4- o 100 C for 1-24 hrs.. The difunctional hydroxyl terminated water-insoluble polymer is such a^ poly propylene glycol and the diester based activator is such as dibutyl tin dilaurate. The component II is cooled and stored under cold condition. The potting compound is then prepared by blending component 1 and component 11 at the mixing ratio of 20:80 to 80:20 totalling 100. The blended components I and II is heated at a temperature of 25- o 100 C for 1-100 mins.. The heated potting compound is dispensed to the hollow fiber module using a dispenser. The potting compound sets to a solid mass after 90-120 mins. under centri- o fugal rotation with 700-900 rpm and temperature of 30-60 C. The demolding is carried out after a duration of 100-180 mins.. The cross 1inkabie and non-aromatic polyurethane prepared by the process (i)-(iii) of the present inventiion is evaluated for various properties as shown in Table 1. Characteristics of cross 1inkabie and non-aromatic polyurethane potting compound Properties Component I Component I I 1. Specific gravity (g/cc) 1.120-1.300 0.900-1.00 o 2. Viscosity at 28 C (cps) 12000-18000 75-200 3. Mixing ratio of component 20:80 to 80:20 I and I I 4. Rheological property Pseudoplastic 5. Viscosity of the 5000-8000 mixture (cps) 6. Setting time 90-120 7. Demold time (minute) 90-180 8. Recommended processing 25-100 o temperature ( C) 9. Shore 'A' hardness of 60-80 cured potting compound The stability of cured potting compound under different sterilisation (increased cycles of autoclaving sterilisation and doses of gamma radiation sterilisation) and various prolonged chemical treatment in formaldehyde and ethanol are evaluated as shown in Table 2. Table 2 Stability of cured potting compound after autoclaving and gamma radiation sterilisation and chemical treatment Weight loss (X) aftr immersion Treatment 24hr 48hr 72hr 96hr 120hr 312hr 556hr 768hr A. Immersion of autoclaved sample in heptane 1. 1 cycle auto- Nil Nil Nil Nil Nil 1.94 1.94 1.95 clav ing 2. 2 cycle auto- Nil Nil Nil Nil Nil 1,69 2.05 2.05 clav ing 3. 3 cycle auto- Nil Nil Nil Nil Nil 1.96 2.53 2.53 claving 4. Control poly- Nil Nil Nil Nil Nil 3.08 4.25 4.25 urethane B. Immersion of gamma radiation sterilised sample in heptane 2.5 Mrad Nil Nil Nil Nil Nil 1.78 1.85 1.9 5 Mrad Nil Nil Nil Nil Nil 1.62 1.97 2.0 7.5 Mrad Nil Nil Nil Nil Nil 1.92 1.90 2.0 C. Immersion of sample Weight loss X after immersion In formalin '■ 72 hr 120 hr 192 hr Nil Nil Nil The basic charateristics of cross 1inkable and non-aromatic potting compound components shown in Table 1 clearly reveals that the viscosity of the mixture is moderate enough to dispense to the hollow fiber module. The setting time and deroold time is also reasonably low. The recommended processing temperature for mixing the components as well as for setting is also low. These charac¬teristics enable fast setting to rigid crosslinked mass. The potting compound being pseudoplas tic, flows through the inter¬stices of the hollow fiber bundle easily under centrifugal rota¬tion without wicking. Therefore, a well defined circular encap¬sulation of fiber bundle inside the module is formed. The encap¬sulation results into a glassy, transparent mass in which the fibers are visibly seen. The crosslinked potted compound has appreciable shore A hardness. The stability of the crosslinked potted compound is also good as there is no weight loss of auto-claved sample in heptane even upto 5 days. The marginal weight loss in prolonged duration with increased cycles of autoclaving is due to the denaturation of fibers in the potted composite. Generally in hospitals, the haemodialyzers are not exposed to such drastic conditions. The haemodia1yzers are generally cleaned with clean water after deproteinization and stored in formalin for removal of micro-organisms. Therefore the present potting compound setting to a crosslinked material is stable enough to meet the hospital requirments. Thus, the cross 1inkable and non-aromatic potting compound prepared by the process of the present invention has the following advantages. 1. The potting compound is prepared from aliphatic diisocyanate instead of aromatic diisocyanate. Thus, the risk of formation of potential carcinogenic chemical is avoided. 2. All the reactants in components I and li are compatible. The components I and 11 react stoichioraetricaIly. Therefore, the final crosslinked potting compound is glassy and transparent. 3. Potting compound is pseudoplastic which enables easy dispen¬sing using conventional dispenser. 4. Potting compound is able to set in short duration without evolving large amount of heat exothermical1y. Therefore, the setting reaction will not affect the hollow fiber bundle. 5. The penetration of potting compound in to the hollow fiber is minimal because of fast viscosity build-up. Therefore clogging of pore at the end of the module is not extensive. 6. The adhesive bonding of hollow fiber bundle and dialyzer module of polymethyl methacrylate is good which ensures no 1eakage. 7. The stability of the crosslinked potting compound is good. It does not produce any amine compounds during routine sterilisation and immersion in formalin. The invention discloses a novel method for the preparation of a new product fo biocomptaible, crosslinkable and non-aromatic potting compound. After a number of detailed experimental studies as discussed above and inference given therein, we have found that the product of the invention has ensured that the objectives of the invention can be easily achieved. The objects of this invention will be more apparent from the ensuing example. (1) Preparation of isocyanate terminated prepolymer of poly- urethane component I potting compound A difunctlonal aliphatic diisocyanate containing an even number of methylene linkages between isocyanate is reacted with a multi¬functional water Insoluble polyol containing ester groups having unsaturation and hydroxy! group in a long chain in the mole ratio o of 1:0.309 at 100 -f 5 C for 30-*- 5 mins. under inert atmosphere. The prepolymer is cooled and stored in air tight amber bottle at o 4 C. (2) Preparation of component II of potting compound The component II consists of a difunctlonal hydroxy! terminated water insoluble polymer having ether group between methylene and OH groups in the main chain and having a molecular weight 1000 ■•' 50 and a diester based activator. These reactants in the ratio o 100:0.01 are blended at 25 -•- 5 C for 10 hrs. and stored in air o tight amber bottle at 4 C. 3. Preparation of potting compound The prepolymer (component I) obtained in step I and component II obtained in step II is reacted partially further with the mixing o ratio of 58.5:41.5 at temperature of 60 '*■ 5 C for 5-10 mins.. The semi-reacted component I and component II is the potting compound. 4. Potting of hollow fibers bundle in the dialyzer module The potting compound under warm condition is dispensed immediately to the dialyzer module using a dispensor. The module Is subjected to centrifugal rotationof 800 + 50 rpm for 90 + 10 o mins., under warming condition at 40 + 2 C. The potting compound set to solid cross!inked, glassy and transparent mass binding all the hollow fiber bundle as well as polymethyl methacrylate dialyzer housing at both ends of the module. WE CLAIM: 1. A cross 1inkable and non-aromatic polyurethane potting compound comprising a blend of component I of isocyanate terminated prepolymer of polyurethane and component II of aliphatic, non- aromatic diisocyanate. 2. A cross 1inkable and non-aromatic polyurethane potting compound as claimed in claim 1 wherein component I and component I I is present in the ratio of 20-80 and 80-20. 3. A cross Iinkab1e and non-aromatic polyurethane potting compound substantially as herein described.

Documents:

0433-mas-2002 abstract duplicate.pdf

0433-mas-2002 abstract.pdf

0433-mas-2002 claims.pdf

0433-mas-2002 claism duplicate.pdf

0433-mas-2002 correspondence-others.pdf

0433-mas-2002 correspondence-po.pdf

0433-mas-2002 description (complete).pdf

0433-mas-2002 description (completed) duplicate.pdf

0433-mas-2002 form-1.pdf

0433-mas-2002 form-19.pdf

0433-mas-2002 form-26.pdf

0433-mas-2002 form-3.pdf

0433-mas-2002 petition.pdf