Title of Invention | A PROCESS FOR THE PREPARATION OF HEPARIN BONDED POLYOLEFIN |
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Abstract | THE PROCESS FOR THE PREPARATION OF HEPARIN BONDED POLYOLEFIN THE STEPS OF CLEANING THE POLYOLEFIN IN AN ORGANIC SHEET POLYPROPYLENE. |
Full Text | FIELD OF THE INVENTION This invention relates to a process for the preparation of heparin bonded olefin polymers and the olefin polymers prepared thereby. BACKGROUND OF THE INVENTION Heparin is a naturaity occurring mucopolysaccharide composed of repeating units of disaccharides. The principal anticoagulant effect of heparin is due to its ability to accelerate the inhibition of thrombin factor Xa by AT HL The effect of heparin on fibrin clot formation extends beyond its direct effect of neutralisation of thrombin and Xa In the absence of heparin or other anticoagulants fibrinogen rapidly coats foreign surfaces and platelets adhere to fibrinogen soon thereafter. Systemic administration of heparin even in enormous doses used for CPB, incompletely prevents adherence of fibrinogen and platelets to synthetic surfaces. Blood coagulation remains active during CPB despite profound anticoagulation with heparin. Protamine activates complement, causes vasodilation and can cause life-threatening anaphylaxis or pulmonary hyper tension In order to reduce the drawbacks of heparinization of blood, attempts were made for the immobilization of heparin on to devices for blood contacting applications. Cardiopulmonary applications like membrane oxygenator, catheters, etc. are a few to mention among them The effect of protein adsorption of the anticoagulant activity of surface immobilised heparin on to carboxyiated polystyrene beads was determined by Vandelden et al (X Biomater. Sci. Polym. Ed 7,8; 727-740, 1996) and was found promising. Different methods of immobilisation of heparin had been attempted. Heparin being a complex macro molecular organic polysaccharides with high negative charges can bind to positively charged matrices. Such ionic binding has been materialised by Eberle, Manton & Meals (J. Biomed Mater. Res.7:145-153,1973), with quaternary ammonium compounds which in turn is bound to synthetic surfaces like polyethylene and poly vinyl chloride. But stability of such ionically linked heparin is poor when compared to covalently bound heparin. Other methods of coating include that with the carbodiimide method Polyvinyl Chloride Heparin has earlier been bound or immobilised with (pVA)to a hydrogel. Other matrices which had been tried to be coated with heparin include ^MMA.) Ajrart from mis, biological substrates like collagen have been immobilised with heparin Poly propylene had been coated with heparin by the Duraflo II (Universal coating) and the platelet adhesion of the coated sample has been studied It has been found that they have better blood compatibility, lesser blood material interaction and micro embolisation prevention capabilities. For universal coating, the physio chemical properties of the unfractionated heparin are modified with a proprietary binding agent The resulting material Duraflo II heparin has high affinity to a variety of synthetic surfaces. They retain all anti-coagulation properties of heparin. Different synthetic materials have been used for the fabrication of devices like Polyvinyl Chloridi polycarbonate (for oxygenator shell), polypropylene (for membrane oxygenator) blood bags), polyethylene (for catheters) and so on. OBJECTS OF THE INVENTION It is therefore an object of this invention to propose heparin bonded polyolefin which does not affect the mechanical properties of me polyolefin. It is a further object of mis invention to propose heparin bonded polyolefin which retains the surface profile of the polymer after modification. Another object of mis invention is to propose heparin bonded potyolefin which is stable. DESCRIPTION OF THE INVENTION Thus according to this invention is provided a process for the preparation of heparin bonded polyolefin comprising the steps of cleaning the polyolefin in an organic solvent and drying, followed by treatment with an oxidizing agent such as an inorganic salt alone or in combination with an acid, and washing the treated sample, introducing the washed treated sample into a diimide solution followed by washing, treatment with a heparin solution, further washing and drying to obtain the heparin bonded polyolefin. According to mis invention is further provided heparin bonded olefin polymers. In accordance with this invention, Polyethylene (PE) sheets of commercial grade or high quality or polypropylene sheets or hollow fibres are cleaned with an organic solvent like Chloroform (CHCI3) Dimethyl acetamide (DMAc), dichloromethane (CH2CI2) or dimethyl sulphoxide (DMSO) or inorganic reagents like hydrogen peroxide nitric acid. The cleaned polymer is dried at 50-130°C for a period of one hour. They are then treated with an oxidising agent of inorganic origin. The inorganic salts that may be used for the purpose are Sodium Nitrate, Sodium Chromate, Potassium permanganate, Sodium peroxide either alone or in combination with other acids such as Nitric acid, Hydrochloric acid or Sulphuric acid of suitable strength. Polyethylene sheets of lxl cm size are cut from large sheets or polypropylene hollow fibres of about 275 microns are cut into strips of about 1 cm in length with a fine scalpel. They are washed with water, dried and introduced into a solution containing about 50- 100% nitric acid, hydrochloric acid or sulphuric acid alone or in combination with about 1-10% by weight of sodium nitrate or potassium dichromate, potassium permanganate, etc.. The treated samples are washed in distilled water. They are introduced into a 5-250 mg% 0.0005gm of the dye was dissolved in .001% wt/wt of HCl containing .002% by wt Of NaCI. 0.0.243gm of the modified hollow fibre sample was put into 5ml of the dye solution. After 30 mins., the samples were taken out A control was done using unmodified polypropylene hollow fibers. On visual examination, a violet colouration was observed on the modified samples which was absent in the unmodified samples. This was due to the attachment of the dye molecules on to the heparin molecules. The absorbance of the remaining dye solution was monitored using a double beam Shimadsu Spectrophotometer at 63 Iran wave length. From a standard curve prepared from known amounts of the dye, the absorbance of the remaining solution from each sample was found out Absorbance of the following samples were measured 1. Reagent blank- "B* (The dye solution used for the dye depletion study) 2. Three control samples "01,02,03" (unmodified control samples of almost equal weight) 3. Three modified samples "M1,M2,M3" (heparin bonded samples of almost equal weight) Load at break The load at break of the modified polypropylene was compared with that of the unmodified sample in a tensile strength testing machine. A single strand of the hollow fibre was cut to a length of about 5cm. It was gripped to the jaws of the testing machine (Instron, Model 1011). The grip speed was set to 200 mm/mia lit was found that the average load at break was 1.71875.Newtons for the unmodified and 1.70S8 Newtons for the modified samples. It was found that there was no remarkable change in the mechanical properties either. Hence, it can be understood that the surface properties and mechanical properties are not affected by the modification. WE CLAIM: 1. A process for the preparation of heparin bonded polyolefin comprising the steps of cleaning the polyolefln in an organic solvent and drying, followed by treatment with an oxidizing agent such as an inorganic salt alone or in combination with an acid, and washing the treated sample, introducing the washed treated sample into a diimide solution followed by washing, treatment with a heparin solution, further washing and drying to obtain the heparin bonded polyolefin. 2. The process as claimed in claim 1 wherein said polyolefln is a polymer such as polyethylene, polypropylene. 3. The process as claimed in claim 1 wherein the polyolefin sample is in the form of sheets or hollow fibres. 4. The process as claimed in claim 1 wherein the organic solvent used for cleaning the polyolefin sample is selected from chloroform (CHCfe), dimethyl sulphoxide (DMSO) 5. The process as claimed in claim 1 wherein the polyolefin is optionally cleaned with hydrogen peroxide or nitric acid. 6. The process as claimed in claim 1 wherein the cleaned polyolefin is dried at 50-130°C. , 7. The process as claimed in claim I wherein said oxidising agent is an inorganic salt such as sodium nitrate, sodium chromate, potassium permanganate, sodium peroxide, sodium dichromate, potassium dicbromate, ammonium persulphate. 8. The process as claimed in claim 1 wherein the acid used is a mineral acid such as nitric acid, hydrochloric acid, sulphuric acid. 9. The process as claimed in claim 1 wherein for die treatment wim the oxidising agent, a 50-100% mineral acid is used with 1 to 10% by weight of the inorganic salt 10. The process as claimed in claim 1 wherein the polyolefin samples, after treatment with the oxidising agent, are washed with distilled water. 11. The process as claimed in claim 1 wherein the diimide compound is l-propyl-3-(3-dipropyl aminopropyl) carbodiimide, 2-ethyl-3-(3-diethyI aminoethyl) carbodiimide, l-ethyl-3-(3-dimediyl aminopropyl) carbodiimide etc. having different carbonyl groups attached to the different nitrogen atoms. 12. The process as claimed in claim 1 wherein the treatment with diimide solution is carried out at apH of 3.5-8.5 of a suitable buffer. 13. The process as claimed in claim 1 wherein the treatment with the diimide solution is carried out over a period in the range of 1 and 15 hrs.. 14. The process as claimed in claim 1 wherein the treatment with the diimide solution is carried out at a temperature in the range of 15 and 5 06C. 15. The process as claimed in claim 1 wherein for the treatment with diimide solution, a 5 to 250 mg% solution is used. 16. The process as claimed in claim 1 wherein the diimide treated polyolefin samples are washed with distilled water. 17. The process as claimed in claim 1 wherein treatment with the heparin solution is carried out at a pH of 3 to 8.5. 18. The process as claimed in claim 1 wherein a solution of heparin is used. ~^ 19. The process as claimed in claim 1 wherein the heparin treated samples after washing, are dried at 30 to 40°C. 20. Heparin bonded polyolefin. > 21. A process for the preparation of heparin bonded polyolefin substantially as herein described and illustrated 22. Heparin bonded polyolefin substantially as herein described and illustrated. Dated this 5th day of NOVEMBER, 2002. |
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0825-mas-2002 claims duplicate.pdf
0825-mas-2002 description (complete) duplicate.pdf
0825-mas-2002 description (complete).pdf
825-mas-2002- correspondence others.pdf
825-mas-2002- correspondence po.pdf
Patent Number | 207533 | ||||||||
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Indian Patent Application Number | 825/MAS/2002 | ||||||||
PG Journal Number | 44/2007 | ||||||||
Publication Date | 02-Nov-2007 | ||||||||
Grant Date | 14-Jun-2007 | ||||||||
Date of Filing | 11-Nov-2002 | ||||||||
Name of Patentee | SREE CHITRA TIRUNAL INSTITUTE FOR MEDICAL SCIENCES & TECHNOLOGY | ||||||||
Applicant Address | SATELMOND PALACE,TRIVANDRUM 695 012. | ||||||||
Inventors:
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PCT International Classification Number | A61K31/725 | ||||||||
PCT International Application Number | N/A | ||||||||
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