Title of Invention

"AN PROCESS FOR THE PREPARATION OF AN IMPROVED POLYMERIC DEVICE"

Abstract

A process for preparation of an improved polymeric device with uniform controlled porosity and containing one or more ingredients which comprises the steps of (i) preparing a polymeric composition comprising 1.76 to 5.28% by weight of one or more soft, fast degrading polymer selected from poly( carboxyphenoxyualeric acid) poly(carboxyphenoxyoctanoic acid) , poly(carboxyphenoxyvaleric-co¬carboxyphenoxyoctanoic acid) and 1.76 to 5.2 8% by weight of one or more rigid, slow-degrading polymers selected from poly (carboxyphenoxyhexane) poly(carboxyphenoxypropane) , poly (carboxyphenoxypropane-co-sebasic acid) and balance volatile organic solvent , preparing devices such as implants , sheets , rings, disc beads from the composition by conventional manner such as herein described, (ii) exposing the device obtained in step(i) to a degradation medium for 10-15 hours to get a porous device, isolating and drying the resultant device thus obtained, (iii) dispersing the resultant porous device in a solution of active ingredients such as described herein, removing the excess solution of active ingredients and drying to get esired the polymeric device.

Full Text

This invention relates to a process for the preparation of polymeric device with uniform, controlled porosity and containing one or more active ingredients using a polymeric composition . More particularly the invention relates to the preparation of a polymeric blend by exposing a polymeric composition to a degradation medium in order to degrade and dissolve away the fast —degrading polymer in the blend, thereby creating porosity in the blend which is proportional to the amount of the fast-degrading polymer in the blend and subsequently loading an active ingredient into these pores. The blends produced by the present process have potential application in the field of controlled release teclmology medicine , agriculture , pesticides, cosmetics , food-stuffs , enzyme immobilization catalysis , biochemical and microbial reaction ,imaging etc. The polymeric composition prepared according to the process disclosed in our above-mentioned co-pending patent application has not been made so far in the prior art, and hence , there are no processes available for the same . Consequently , no process is mown in the prior art for the preparation of porous , biodegradable , polymeric blend by the subsequent processing of the said blend as described in the present invention. Accordingly the present invention provides a process for preparation of an improved polymeric device with uniform , controlled porosity and containing one or more ingredients which comprises the steps of (i) preparing a polymeric composition comprising 1.76 to 5.28% by weight of one or more soft, fast degrading polymer selected from poly( carboxyphenoxyualeric acid) , poly(carboxyphenoxyoctanoic acid) poly(carboxyphenoxyvaleric-co-carboxyphenoxyoctanoic acid ) and 1.76 to 5.28% by weight of one or more rigid , slow-degrading polymers selected from poly(carboxyphenoxyhexane) , poly( carboxyphenoxypropane) , poly( carboxyphenoxypropane-co-sebasic acid) and balance volatile organic solvent , preparing devices such as implants , sheets , rings , disc , beads from the composition by conventional manner such as herein described , (ii)exposing the resultant device to a degradation medium for 10-15 hours to get a porous device , isolating and drying the resultant device thus obtained, (iii) dispersing the resultant device in a solution of active ingredients such as herein described , removing the excess solution of active ingredients and drying to get desired the polymeric device. In one of the embodiments of the present invention , the process comprises of exposing, dried polymeric composition prepared by the process of present invention to an aqueous degrading medium , allowing the fast degrading polymer in the blends to degrades completely, washing off the degradation products, isolating and drying porous blends thus obtained , soaking them in the solution or dispersion of active ingredients till the pores are filled , decanting off the excess solution or dispersion and drying the devices either by freeze —drying or by the application of vacuum. In another embodiment of the present invention , the process comprises of exposing the dry polymer devices such as implants , discs , sheets , rings , beads by injecting through hypodermic needle into liquid paraffin or aqueous solution of poly(vinyl alcohol) , drying the devices thus obtained and dispersing the resultant devices into an aqueous degrading medium, allowing the fast degrading polymer in the device to degrade completely, washing off the degradation product , isolating and drying the porous device thus obtained, soaking them in the solution or dispersion of the dctive ingredients till the pores are filled, decanting off the excess solution or dispersion, and drying the devices either by freeze-drying or by the application vacuum. in still another embodiment of the present invention, the degradation medium is selected from aqueous alkali solutions or alkaline buffer solutions, aqueous acid solutions or acidic buffer solutions. In yet another embodiment of the present invention, the active ingredients are selected from drugs, dyes, proteins, peptides, vaccines, hormones, steriods, enzymes, microorganisms, catalysts, flavors, nutrients, tracers, inhibitors, promoters, etc. or their compatible mixtures thereof The present invention is described herein below by examples which are illustrative only and should not be construed to restrict the scope of the present invention in any matter. Example 1 100 mg of poly (carboxyphenoxyvaleric acid) and 100 mg of poly (carboxyphenoxyhexane) were dissolved in 2 ml of dichioromethane to get a clear, homogeneous solution. This solution was injected through a hypodermic needle into 80 ml of liquid paraffin containing 10 per cent dichloromethane and 8 per cent sorbitan monooleate and ke~ptstirred at 400 rpm in a round-bottom flask. After 5 mm, 100 ml of petroleum ether was added over 20 mm. The hardened microspheres were isolated by filtering, washed with petroleum ether, and dried at room temperature for 2 hours under vacuum. These dried microspheres were stirred in 20 ml of 0.01 N sodium hydroxide solution for 12 hours. The microspheres were filtered, washed, and dried at room temperature for 8 hours over frised calcium chloride under vacuum. These microspheres were immersed in 5 ml of a 10% solution of p-nitrophenol in distilled water taken in a stoppered test tube. A few cycles of applying and releasing of vacuum were carried out on the system with intermittent swirling of the test tube. The microspheres were allowed to settle down and the supernatant solution was removed. The microspheres were then freeze-dried. Example-2 50 mg of poly(carboxyphenoxyvaleric acid) and 150 mg of poly(carboxyphenoxy¬hexane) were dissolved in 2 ml of dichloromethane to get a clear, homogeneous solution. The solution is then injected through a hypodermic needle into 80 ml of 0.5 per cent aqueous solution of poly(vinyl alcohol) which was stirred at 400 rpm in a round-bottom flask. 5 mm after the addition of the solution, vacuum was applied to the system for one and a half hours. The poly(vinyl alcohol) solution was then diluted with distilled water, and the hardened microspheres were washed and stirred in 20 ml of 0.01 N sodium hydroxide solution for 12 hours. The microspheres were filtered. washed, and dried at room temperature for 8 hours over fused calcium chloride under vacuum. These microspheres were immersed in 5 ml of a 10% solution of the dye. Brilliant Blue BL. in distilled water taken in a stoppered test tube. A few cycles of applying and releasing of vacuum were carried out on the system with intermittent swirling of the test tube. The microspheres were allowed to settle down and the supernatant solution was removed. The microspheres were then freeze dried. Example-3 125 mg of poly(carboxyphenoxyvaleric acid) and 375 mg of poly(carboxyphenoxv¬hexane) were taken in a glass cup of 2 ml capacity. The cup was heated to l70~~C. After the polymers melted, the contents were mixed well and dispersed into 30 ml of stirred silicone oil maintained at 1700C in a 100 ml beaker. After 3 mm. heati~1~ was stopped and the dispersion was allowed to cool to room temperature under continuous stirring. The silicone oil was diluted with petroleum ether and the microspheres were filtered, washed, and dried under vacuum for 2 hours. These dried microspheres were stirred in 30 ml of 0.01 N sodium hydroxide solution for 12 hours. The microspheres were filtered, washed, and dried at room temperature for 8 hours over fused calcium chloride under vacuum. These microspheres were immersed in 5 ml of a 10% solution of p-nitrophenol in distilled water taken in a stoppered test tube. A few cycles of applying and releasing of vacuum were carried out on the system with intermittent swirling of the test tube. The microspheres were allowed to settle down and the supernatant solution was removed. The microspheres were then freeze-dried. Example-4 125 mg of poly(carboxyphenoxyvaleric acid) and 375 mg of polv(carboxvphenoxv¬hexane) were taken in a glass cup of 2 ml capacity. The cup was heated to VO ~C. After the polymers melted, the contents were mixed well and dispersed into 30 nil of stirred silicone oil maintained at 1700C in a 100 ml beaker. After 3 mm. heating 'vas stopped and the dispersion was allowed to cool to room temperature under continu¬ous stirring. The silicone oil was diluted with petroleum ether and the micros~neres were filtered, washed, and dried under vacuum for 2 hours. These iried microspheres were stirred in 30 ml of 0.01 N sodium hydroxide solution for 12 hours. The microspheres were filtered, washed, and dried at room temperature §or S hours over fused calcium chloride under vacuum. These microspheres were immersed in 2 ml of a 5% solution of lysozyme in distilled water taken in a stoppered test tube. A few cycles of applying and releasing of vacuum were carried out on the system with intermittent swirling of the test tube. The microspheres were allowed to settle down and the supematant solution was removed. The microspheres were then freeze-dried. Example-5 125 mg of poly(carboxyphenoxyvaleric acid) and 375 mg of poly(carboxyphenoxy¬hexane) were taken in a glass cup of 2 ml capacity. The cup was heated to 1 700C. After the polymers melted, the contents were mixed well and dispersed into 30 ml of stirred silicone oil maintained at 1700C in a 100 ml beaker. After 3 mm, heating was stopped and the dispersion was allowed to cool to room temperature under continu¬ous stirring. The silicone oil was diluted with petroleum ether and the microspheres were filtered, washed, and dried under vacuum for 2 hours. These dried micro-spheres were stirred in 30 ml of 0.01 N sodium hydroxide solution for 12 hours. The microspheres were filtered, washed, and dried at room temperature for 8 hours over fused calcium chloride under vacuum. These microspheres were immersed in 5 ml of a 5% solution of p-nitrophenol in methanol taken in a stoppered test tube. A few cycles of applying and releasing of vacuum were carried out on the system with intermittent swirling of the test tube. The microspheres were allowed to settle down and the supematant solution was removed. The microspheres were then dried under vacuum at room temperature. Example-6 250 mg of poly(carboxyphenoxyvaleric acid) and 750 mg of poly(carboxyphenoxy¬hexane) were mixed and packed compactly into a wire-extruding die of 0.5 cm internal diameter and 0.5 mm orifice diameter. The inner surface of the die was wetted with liquid paraffin before packing the polymer-dye mixture. The die was heated to 1600C using band heaters. After the polymers melted, the melt was extruded into a cooling bath containing liquid paraffin. The solidified extrudate was washed with n-hexane, dried, and cut into pellets of 3 mm length. These pellets were stirred in 50 ml of 0.01 N in sodium hydroxide solution for 12 hours. The pellets were filtered, washed, and dried at room temperature for 8 hours over fused calcium chloride under vacuum. These pellets were immersed in 5 ml of a 5% aqueous solu¬tion of p-nitrophenol taken in a stoppered test tube. A few cycles of applying and releasing of vacuum were carried out on the system with intermittent swirling of the test tube. The supernatant solution was removed. The pellets were then freeze-dried. We claim: 1. A process for preparation of an improved polymeric device with uniform controlled porosity and containing one or more ingredients which compnses the steps of (i) preparing a polymeric composition comprising 1.76 to 5.28% by weight of one or more soft, fast degrading polymer selected from poly( carboxyphenoxyualeric acid) , poly(carboxyphenoxyoctanoic acid) , poly(carboxyphenoxyvaleric~cO~carbOXyPhenOXyOctanOic acid) and 1.7o to 5.28% by weight of one or more rigid , slow-degrading polymers selected from poly(carboxyphenoxyhexane) , poly( carboxyphenoxypropane) , poly( carboxyphenoxypropane -cc-Seba~~c acid) and balance volatile organic solvent , preparing devices such as implants , sheets , rings , disc , beads from the composition by conventional manner such as herein described, (ii) exposing the device obtained in step(i) to a degradation medium for 10-15 hours to get a porous device, isolating and drying the resultant device thus obtained, (iii) dispersing the resultant porous device in a solution of active ingredients such as herein described, removing the excess solution of active ingredients and drying to get desired the polymeric device. 2. A process as claimed in claim I wherein the degradation medium is selected from aqueous alkali solutions or alkaline buffer solutions , aqueous acid solutions or acidic buffer solutions. 3. A process for the preparation of polymeric device with uniform, controlled porosity and containing one or more active ingredients as substantially described hereinbefore with reference to examples.

Documents:

1771-del-1998-abstract.pdf

1771-del-1998-claims.pdf

1771-del-1998-complete specification [granted].pdf

1771-del-1998-correpondence-others.pdf

1771-del-1998-correpondence-po.pdf

1771-del-1998-description (complete).pdf

1771-del-1998-form-1.pdf

1771-del-1998-form-2.pdf

1771-del-1998-form-4.pdf