WO2011019631A1 - Semi-crystalline, fast absorbing polymer formulation - Google Patents
Semi-crystalline, fast absorbing polymer formulation Download PDFInfo
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- WO2011019631A1 WO2011019631A1 PCT/US2010/044836 US2010044836W WO2011019631A1 WO 2011019631 A1 WO2011019631 A1 WO 2011019631A1 US 2010044836 W US2010044836 W US 2010044836W WO 2011019631 A1 WO2011019631 A1 WO 2011019631A1
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/66—Polyesters containing oxygen in the form of ether groups
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
- C08G63/08—Lactones or lactides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/60—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from the reaction of a mixture of hydroxy carboxylic acids, polycarboxylic acids and polyhydroxy compounds
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2261/00—Macromolecular compounds obtained by reactions forming a carbon-to-carbon link in the main chain of the macromolecule
- C08G2261/10—Definition of the polymer structure
- C08G2261/12—Copolymers
- C08G2261/126—Copolymers block
Definitions
- the present invention relates to a composition
- a composition comprising a semi-crystalline, absorbable copolymer formulation wherein the first component is hydroxy-capped polycondensation product of diglycolic acid and a mixture of two diols, diethylene glycol (DEG) and ethylene glycol (EG), with DEG added in larger molar amount, and wherein the second component, glycolide is incorporated during the subsequent ring-opening polymerization.
- DEG diethylene glycol
- EG ethylene glycol
- the resulting hydrophilic resin has low crystallinity level, glass transition temperature, Tg slightly below room temperature, and may be particularly useful for making fibers, microspheres, or melt blown nonwoven constructs or other medical devices where fast hydrolysis rates and superior mechanical properties are desirable.
- Mechanical properties of a medical device can be made to vary depending on the end use application for the device. For example, it is often desirable for surgical sutures to exhibit mechanical strength, such as straight tensile strength and knot tensile strength.
- One technique for producing surgical sutures having these desired properties is to utilize polymers having some degree of crystallinity. Specifically, the crystalline or ordered structure of the polymer imparts strength to a medical device produced therefrom, including but not limited to a surgical suture, surgical mesh, surgical staple, haemostatic clip, and the like.
- a second approach to increase the absorption or hydrolysis rate of synthetic absorbable polymers is to add a non-absorbable hydrophilic moiety, e.g. a polyether such as polyethylene glycol (PEG), to increase the hydrophobicity of absorbable polymer.
- a polyether such as polyethylene glycol (PEG)
- PEG polyethylene glycol
- a third approach is to use a pre-degraded synthetic absorbable polymer.
- an absorbable polymer may be subjected to a hydration step or gamma irradiated to initiate the hydrolysis of the absorbable polymer, thereby resulting in a pre-degraded product.
- problems arising with the use of a pre-degraded synthetic absorbable polymer include difficulty in controlling the quality and stability of the pre-degraded polymer. More specifically, it may be difficult to achieve reproducible levels of pre-degradation in the final product.
- U.S. Patent Publication 2006/0051398, assigned to Ethicon, Inc. describes a copolyester comprising the reaction product of a polycondensation polyester and at least one lactone, wherein the polycondensation polyester comprises the reaction product of diglycolic acid and/or a derivative thereof and ethylene glycol.
- the product described in this reference is useful for adhesion prevention.
- this reference indicates that its composition is absorbable, the copolyester described in this reference is fully amorphous with relatively low molecular weight. Therefore, it is not expected that a medical device made from this copolyester will have the requisite physical properties of strength required, for example, for surgical sutures.
- U.S. Pat. No. 5,644,002 also assigned to Ethicon, Inc., describes absorbable polymers and blends of polycondensation polyester and aliphatic polyesters based on lactone monomers, where the polycondensation polyester is the reaction product of diglycolic acid and an alcohol selected from selected from the group consisting of glycerol, pentaerythitol, trimethylolpropane, hydroxyl terminated poly(ethylene glycol)s, ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,4-butylene glycol, dipropylene glycol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, and 1,8-octanediol.
- the absorbable polymers described in this reference are branched or crosslinked fully amorphous soft materials and as such, are not expected to produce a medical device having the requisite physical properties
- U.S. Pat. Nos. 4,048,256, 4,095,600 and 4,122,129 assigned to American Cyanamid Company, describe biocompatible and absorbable polycondensation polyesters, which are the polycondensation product of diglycolic acid and glycols such as ethylene glycol, diethylene glycol, 1,2-propylene glycol, 1,3-propylene glycol, and the like.
- U.S. Pat. No. 4,095,600 describes a transesterification reaction product of (a) about 2 to 50% by weight of a
- polycondensation polyester made of diglycolic acid and an unhindered glycol and (b) polyglycolic acid (PGA) of molecular weight above 30,000 Daltons before reaction.
- PGA polyglycolic acid
- BLOCKY refers to polymeric structures containing many repeating units of the same monomer, for instance, glycolic acid, linked by covalent bonding.
- polycondensation product is reacted in the second, ring-opening stage with a glycolide, a copolymer with lower crystallinity is formed even in formulations containing higher glycolide content.
- Higher glycolide presence contributes to higher Tg, so the fibers made from this material are likely to exhibit less elasticity.
- composition comprising a co-polyester comprising the reaction product of a polycondensation polyester and at least one lactone, wherein the polycondensation polyester comprises the reaction product of diglycolic acid and/or a derivative thereof with diethylene glycol and ethylene glycol wherein the molar ratio of diethylene glycol to ethylene glycol is in the range from about 2:1 to 4:1; and wherein the co-polyester comprises about 30 to 50% by weight of the polycondensation polyester based on the total weight of the co-polyester and comprises a crystallinity ranging from 10 to 50%.
- the present invention relates to a composition
- a composition comprising a semi-crystalline, absorbable copolyester of a polycondensation polyester and at least one lactone, more specifically, a semi- crystalline absorbable copolyester comprising the reaction product of poly(ethylene-co- ethoxyethylene diglycolate) (PEDG-21) and at least one lactone, where the copolyester comprises about 30 to 50% by weight of the poly(ethylene-co-ethoxyethylene diglycolate) based on the total weight of the copolyester.
- PEDG-21 poly(ethylene-co- ethoxyethylene diglycolate)
- PEDG-21 Poly(ethylene-co-ethoxyethylene diglycolate)
- the copolyester comprises the reaction product of a polycondensation polymer and at least one lactone, wherein the polycondensation polyester comprises the reaction product of diglycolic acid and/or a derivative thereof with ethylene glycol and diethylene glycol.
- the polycondensation polyester comprises the reaction product of diglycolic acid and/or a derivative thereof, up to about 25 mole percent of an aliphatic diacid based on the total moles of acid, ethylene glycol and diethylene glycol.
- the aliphatic diacid may be an aliphatic alpha-omega dicarboxylic acid, including but not limited to 3,6-dioxaoctanedioic acid, 3,6,9-trioxaundecanedioic acid, and combinations thereof.
- the polycondensation polyester may be synthesized by conventional techniques. For example, in a condensation polymerization, diglycolic acid with ethylene glycol and diethylene glycol may be polymerized in the presence of a catalyst at elevated temperatures and reduced pressures. A variety of catalysts may be used, but organometallic compounds have been found to be useful.
- the catalyst for the polycondensation step of the synthesis is preferably tin based, e.g., stannous octoate.
- the most desirable catalyst is dibutyltin oxide and is present in the diglycolic acid/diethylene glycol/ethylene glycol monomer mixture at a sufficiently effective molar ratio of monomer to catalyst, e.g., ranging from about 5,000/1 to about 100,000/1. For example, the ratio of 10,000/1 has been found to be quite suitable.
- the reaction is typically carried out at a temperature range from about 100. degree. C. to about 220. degree. C, preferably from about 140. degree. C. to about 200. degree. C, under an inert atmosphere until esterification of diglycolic acid is complete.
- 180. degree. C. has been found to be a desirable reaction temperature when employing a vertically stirred reactor. It should be noted that the optimum reaction temperature may be reactor and catalyst level dependent but can be found by one having only ordinary skill through the use of experiments.
- the first stage of the polycondensation reaction (inert gas at atmospheric pressure) is followed by polymerization under reduced pressure until the desired molecular weight and viscosity are achieved.
- the weight average molecular weight of the polycondensation polymer can range from about 10,000 to about 50,000 g/mol, preferably from about 30,000 to about 50,000 g/mol, most preferably about 40,000 g/mol. This corresponds to an inherent viscosity range from about 0.70 to about 1.2 dL/g.
- the molecular weight of the polycondensation polymer is lower than about 20,000 g/mol, the molecular weight of the final copolyester is too low to achieve the desired mechanical properties, for example, for suture applications.
- molecular weight can be increased with increasing reaction time, it becomes increasingly difficult to achieve very high molecular weight.
- the weight average molecular weight of the polycondensation polymer can range from about 5,000 to about 15,000 g/mol, preferably from about 8,000 to about 12,000 g/mol, most preferably about 10,000 g/mol. This corresponds to an inherent viscosity range from about 0.30 to about 0.40 dL/g.
- the molecular weight of the polycondensation polymer is lower than about 5,000 g/mol, the molecular weight of the final copolyester is too low to achieve the desired mechanical properties.
- a molecular weight of the polycondensation polymer greater than about 15,000 g/mol is unnecessary to achieve desirable properties.
- this value is not an absolute bar.
- the weight average molecular weight of the polycondensation polymer can range from about 10,000 to about 40,000 g/mol, preferably from about 20,000 to about 30,000 g/mol, most preferably about 25,000 g/mol.
- the molecular weight of the polycondensation polymer is lower than about 10,000 g/mol, the molecular weight of the final copolyester is too low to achieve the desired mechanical properties.
- a molecular weight of the polycondensation polymer greater than about 40,000 g/mol is unnecessary to achieve desirable properties.
- this value is not an absolute bar.
- PEDG-21 Poly(ethylene-co-ethoxyethylene diglycolate)
- the resultant polycondensation product contains hydroxyl-capped end groups, and is then capable of serving as a macroinitiator in the subsequent, second stage ring- opening polymerization with a lactone monomer, such as glycolide.
- a lactone monomer such as glycolide.
- block glycolide sequences form and the resultant copolyester becomes a crystallizable material. More specifically, this results in a semi-crystalline copolyester, which are properties that are particularly advantageous, for example, in fiber manufacturing processes.
- both the PEDG-21 and the copolyester product derived therefrom are hydrophilic and fast-absorbing polymers.
- the amount of polycondensation polyester used to prepare the copolyester of the present invention ranges from about 30 to 50% by weight based on the total weight of the copolyester.
- the copolyester may comprise the reaction product of a
- polycondensation polyester such as poly(ethylene-co-ethoxyethylene diglycolate) and a lactone such as glycolide.
- the copolyester may comprise the reaction product of a polycondensation polyester and two or more lactones.
- the copolyester may comprise the reaction product of the polycondensation polyester, at least 75 mole percent glycolide based on the total moles of lactone, and a second lactone monomer.
- the copolyesters of the present invention may be conveniently synthesized by reaction of a dihydroxy poly(alkylene diglycolate) homopolymer or copolymer with a lactone by conventional techniques using conventional processes.
- the polycondensation polyester is used as an alpha-, omega- dihydroxy macroinitiator in a subsequent ring opening polymerization (ROP) with a lactone or a lactone mixture.
- the lactone monomers are copolymerized into the polycondensation polyester in the presence of a conventional organometallic catalyst at elevated temperatures.
- the catalyst for the ROP may be already present as residual catalyst in the polycondensation polyester or may be additional catalyst added in this second step of the synthesis.
- a suitable catalyst added at the time of the ROP can be an organometallic catalyst.
- the ring-opening organometallic catalyst is preferably tin based, e.g., stannous octoate, and is present in a sufficiently effective amount in the monomer mixture, preferably at a molar ratio of lactone monomer-to-catalyst ranging from about 20,000/1 to infinity (i.e. no additional catalyst used).
- tin-IV compound such as dibutyltin oxide
- diglycolic acid-to-catalyst ratio of about 10,000/1
- a tin-ll compound such as stannous octoate at a lactone-to-added-catalyst molar ratio of about 240,000/1 at the time of the ring opening polymerization.
- the copolyesters of the present invention may be synthesized alternately with no additional catalyst being added at the time of the ROP.
- the ROP step can be immediately conducted in the same reactor as that used to synthesize the polycondensation polyester immediately after the completion of the polycondensation step, if the reactor can provide adequate heat transfer and agitation.
- the lactone or lactone mixture can be added as a solid, a slurry, or in molten form.
- the ROP can be conducted in a separate reactor at a later date, or in the reactor used for the polycondensation polyester at a later date. If this is the case, the polycondensation polyester is discharged from its reactor and is stored in an environment that minimizes water pick up and hydrolysis. In the case of adding glycolide monomer, the monomer can be added as a solid. The reactor is closed and the pressure reduced.
- the reactor is usually held under vacuum for a prolonged period of time, for instance overnight, to allow drying. Nitrogen is then introduced into the reactor to bring the pressure to slightly greater than one atmosphere, and the purge cycle repeated for a total of three times.
- the temperature of the reaction mass is brought up to 130. degree. C. Once at this temperature, the agitator is activated. The temperature is then increased to 150. degree. C. to complete the mixing.
- This mixing step is essential to produce the copolyesters of the present invention as inadequate mixing tends to allow the formation of homopolymer sequences which can then crystallize to an extent greater than optimum.
- in-situ spectroscopic probes such as Near-Infrared
- reaction temperature is quickly brought up to the final reaction temperature, with 210. degree. C. being a most preferred temperature, and held there for typically 2 hours.
- the exact reaction conditions will depend on the catalyst and its level; final reaction temperatures can vary from about 195. degree. C. to 235. degree. C, and more preferably from about 200. degree. C. to about 220. degree. C.
- Reaction times can vary from about 30 minutes to a few hours, depending on the catalyst and it level, and is typically conducted until the desired conversion of monomer to polymer is achieved.
- polycondensation polyester is added first, typically as a molten stream and the reactor evacuated.
- the reactor is heated to 130. degree. C.
- Molten glycolide (or other glycolide rich mixture) at a temperature of 100. degree. C. is added to the reactor. Although the batch temperature drops slightly, it is quickly brought back up to 130. degree. C. at which point mixing is started. At this point, the process that was described above is followed.
- the copolyesters of polycondensation polyester and lactones will typically have a weight average molecular weight of about 15,000 g/mol (a.k.a.
- the weight average molecular weight is about 40, 000 g/mol to about 200,000 g/mol preferably about 50,000 g/mol to about 80,000 g/mol, and more preferably about 60,000 g/mol to about 80,000 g/mol.
- molecular weights are sufficient to provide an effective inherent viscosity, typically between about 1.0 to about 3.0 deciliters per gram (dL/g), preferably about 1.2 to about 2.0 dL/g, more preferably about 1.4 to about 1.8 dL/g, as measured in a 0.1 g/dL solution of hexafluoroisopropanol (HFIP) at 25 degrees C.
- HFIP hexafluoroisopropanol
- the copolyesters of polycondensation polyester and lactones will typically have a weight average molecular weight of about 25,000 g/mol (a.k.a. Daltons) to about 70,000 g/mol, preferably about 30,000 g/mol to about 60,000 g/mol, and more preferably about 40,000 g/mol to about 55,000 g/mol.
- molecular weights are sufficient to provide an effective inherent viscosity, typically between about 0.5 to about 1.8 deciliters per gram (dL/g), preferably about 0.8 to about 1.4 dL/g, more preferably about 1.0 to about 1.3 dL/g, as measured in a 0.1 g/dL solution of hexafluoroisopropanol (HFIP) at 25 degrees C.
- dL/g deciliters per gram
- HFIP hexafluoroisopropanol
- crystallinity of the copolyester described herein in general, ranges from about 10 to about 50% crystallinity.
- the crystallinity of the copolyester described herein ranges from about 10 to about 40 %, preferably from about 20 to about 40 %, and more preferably from about 20 to about 30%. In the case of microspheres, the crystallinity of the copolyester described herein ranges from about 10 to about 25% crystallinity, and preferably from about 15 to about 20%. In the case of non-woven constructs, the crystallinity of the copolyester described herein ranges from about 10 to about 50% crystallinity, and preferably from about 20 to about 40%.
- the copolyester having the weight average molecular weights described herein may be extruded into fibers or sutures for use in a surgical wound site or trauma site, or used to make other medical devices such as meshes.
- articles may be molded from the copolyester described herein by various conventional injection and extrusion molding processes.
- the copolyester may be molded to form, without limitation, sutures, meshes, films, melt-blown nonwoven constructs, orthopedic devices and injection molded devices.
- the copolyester may be a component of a medical device, i.e., the copolyester may form one layer of a multi-laminate hernia repair mesh, or may be suspended in a polymer solution and coated onto at least a portion of a medical device.
- Example 1 Synthesis of hydroxy terminated Poly(ethylene-co-ethoxyethylene diglycolate) (PEDG- 21) produced using the mixture of two diols.
- the polycondensation product is a fully amorphous, colorless viscous liquid with a glass transition temperature of -11.0 0 C. Weight average molecular weight was 32,000 g/mol. NMR analysis indicated that DEG to EG molar ratio was 78 to 22%, respectively.
- PEDG-21 Poly(ethylene-co-ethoxyethylene diglycolate)
- Example 2 The copolymerization of an ⁇ , ⁇ -dihydroxy Poly(ethylene-co-ethoxyethylene diglycolate) homopolymer with a lactone monomer, glycolide.
- the polycondensation polyester (8.2 kg) produced as described in Example 1 was held in the Benco reactor at room temperature under nitrogen.
- a stainless steel melt-tank was used to melt the crystalline glycolide, prior to the addition into the reactor.
- the glycolide (12.3 kg) was charged to the melt-tank, pulled under vacuum, and then heated and held under nitrogen at 120 0 C.
- the polycondensation polyester was heated to approximately 120 0 C, at which point the molten glycolide monomer was transferred from the melt tank with agitation. No additional catalyst was added in this step of the process.
- Agitator mixing was continued (20 RPM) and the batch temperature raised to 225°C for a short period, to assure that there was no PGA "freeze-up".
- a real-time Fourier Transform Near-Infrared probe was used to confirm complete mixing of components. The temperature was then reduced to 210 0 C and the reaction was continued for another two hours.
- the discharged co-polyester was semi- crystalline, with a slightly yellow tint.
- the copolymer was sized to approximately 3/16" granules in a rotating knife granulator, sieved to remove fines, and placed in a Patterson-Kelley twin-shell tumble dryer.
- the resin was subjected to full vacuum at ambient temperature for approx. 18 hours, at which point heat was introduced to the dryer.
- the dryer was heated to 110 0 C for approximately 24 hours with full vacuum ( ⁇ 200 mtorr) at which point the heat was removed, and the vessel allowed to cool to room temperature.
- the resin was removed from the dryer, placed in vacuum containers and held under vacuum until further use.
- the sources of tin in Example 2 result in a lactone-to-total-tin-catalyst ratio of about 33,800/1.
- the dried resin has a glass transition temperature of 18.0 0 C, as determined by DSC with the heating rate of 10°C/min. Weight average molecular weight was approximately 60,000 g/mol and an inherent viscosity of 1.60 dL/g, as determined in HFIP at 25°C at a concentration of 0.1 g/dL, was recorded. The composition was confirmed by H 1 NMR to be 40/60 by weight poly(ethylene-co- ethoxyethylene diglycolate-co-glycolide). Melt Index (Ml) examination of the resin at 225°C using the load of 3700 g revealed the value of 0.31 g/10 min.
- Example 3 Analytical Characterization of the Copolymer Produced in Example 2.
- the dried copolymer resin (7.32 mg) as described in Example 2 was placed into a DSC pan, quenched below -40 0 C, and heated at the constant heating rate of 10°C/min to determine its crystallization properties.
- the major melting point, Tm is located at 178°C, with a multiple smaller peaks found at lower temperatures.
- the heat of fusion, ⁇ Hm is found to be 25 J/g, which corresponds approximately to 25 % of crystallinity.
- Lower melting point and lower crystallinity level found for this material indicate more randomized glycolide sequences than in copolymers described in US 2008103284A1.
- the resin was melted at 225°C, and then subjected to controlled cooling rate step (- 10°C/min) to determine its crystallization properties upon cooling.
- the crystallization peak was located at 100 0 C, with the ⁇ Hc of 22 J/g.
- the copolymer resin described in example 2 was extruded through the Melt Index apparatus (at 225°C), unoriented fiber parts collected, and then subjected to manual cold drawing process until the fibers were fully stretched with an lnstron apparatus according to ASTM D5035 and ASTM D5034, the entire disclosures of which are incorporated by references.
- Pieces of drawn fiber were analyzed by DCS to determine their crystallization properties. It was found that the glass transition temperature of the cold drawn fiber is 20 0 Q while the broad melting peak is located at 173°C.
- the heat of fusion, ⁇ Hm is 28 J/g, which corresponds to about 28 % crystallinity.
- PEEDG/Gly 40/60 copolymer i.e., copolymer in ratio of 40 weight % PEEDG to 60 weight % glycolide
- DEG diol alone first row in Table 1
- Tg 13°C
- This composition is the same composition made in Example 2 of US20080103285, the disclosure of which is incorporated by reference.
- PEDG/Gly 40/60 copolymer i.e., copolymer in ratio of 40 weight % PEDG to 60 weight% glycolide
- EG diol alone second row in Table 1
- This composition is the same composition made in Example 2A of US20060051398, the disclosure of which is incorporated by reference.
- PEDG21/Gly 40/60 copolymer i.e., copolymer in ratio of 40 weight % PEDG21 to 60 weight % glycolide
- PEDG21/Gly 40/60 copolymer made from both diols, DEG/EG, in the molar ratio of 3:1 in the first polycondensation stage of the synthesis
- unexpectedly exhibits ideal properties for fast absorbing monofilament applications such as:
- the Tg would be low enough, so that the produced fibers will be too elastic as demonstrated by high elongation-to-break values (50-80%) observed for PEEDG/Gly copolymers as determined by tensile testing using an lnstron apparatus according to ASTM D5035 and ASTM D5034, the entire disclosures of which are incorporated by references.
- the mole ratio of DEG to EG in the prepolymer is less than 2:1 (e.g. 1.5:1), it would be expected that in most compositions a fully amorphous polymer would result, which is not suitable for fiber production.
- the mole ratio of DEG to EG in the prepolymer is considerably larger than 4:1 (e.g. 5:1), the amount of EG in the structure would be probably too low to produce any measurable effect (on reducing crystallinity), so the resin would behave as PEEDG/Gly copolymers.
- the preferred crystallinity range for fiber applications is from 20 to 30%, below 20% the fiber may not be dimensionally stable, above 30% monofilaments may be slow to hydrolyze;
- compositions of this invention are characterized by crystallinity levels no higher than 50%, a glass transition temperature, Tg , slightly below or at room temperature, and are expected to be useful for making monofilaments, multifilaments, microspheres, or melt blown nonwoven constructs or other medical devices where fast hydrolysis rates and superior mechanical properties are desirable.
- the following approximate reactant and /or physical property ranges for compositions of this invention are those wherein the molar ratio of diethylene glycol to ethylene glycol is in the range from about 2:1 to 4:1 and preferably from 2.5:1 to 3.5:1 for fiber applications; and wherein the co-polyester comprises about 30 to 50% by weight of the polycondensation polyester based on the total weight of the co-polyester; and wherein the copolymers of this invention comprise crystallinity levels ranging from 10 to 50%, preferably from about 20 to about 40% crystallinity for non-woven constructs, preferably from about 20 to 30% crystallinity for fiber embodiments, and preferably from about 15 to 20% crystallinity for microsphere embodiments.
- compositions of this invention may further comprise therapeutic agents and active substances , including without limitation, antiinfectives, such as antibiotics, antimicrobial agents (e.g. lauric arginate, Diiodomethyl-p-tolyl sulfone, silver and silver compounds, 2,4,4'- Trichloro-2'-Hydroxydiphenyl Ether or combination thereof ) and antiviral agents; analgesics and analgesic combinations; anorexics; antihelmintics; antiarthritics; antiasthmatic agents;
- antiinfectives such as antibiotics, antimicrobial agents (e.g. lauric arginate, Diiodomethyl-p-tolyl sulfone, silver and silver compounds, 2,4,4'- Trichloro-2'-Hydroxydiphenyl Ether or combination thereof ) and antiviral agents; analgesics and analgesic combinations; anorexics; antihelmintics; antiarthritics; antias
- anticonvulsants include antidepressants; antidiuretic agents; antidiarrheals; antihistamines;
- antiinflammatory agents include antimigraine preparations; antinauseants; antineoplastics;
- antiparkinsonism drugs include antipruritics; antipsychotics; antipyretics, antispasmodics; anticholinergics; sympathomimetics; xanthine derivatives; cardiovascular preparations including calcium channel blockers and beta-blockers such as pindolol and antiarrhythmics; antihypertensives; diuretics;
- vasodilators including general coronary, peripheral and cerebral; central nervous system stimulants; cough and cold preparations, including decongestants; hormones, such as estradiol and other steroids, including corticosteroids; hypnotics; immunosuppressives; muscle relaxants;
- procoagulant such as prothrombin, thrombin, fibrinogen, fibrin, fibronectin, heparinase, Factor X/Xa, Factor Vll/Vlla, Factor IX/IXa, Factor Xl/Xla, Factor Xll/Xlla, tissue factor, batroxobin, ancrod, ecarin, von Willebrand Factor, collagen, elastin, albumin, gelatin, platelet surface glycoproteins, vasopressin, vasopressin analogs, epinephrine, selectin, procoagulant
Abstract
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Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
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CN2010800362144A CN102471468A (en) | 2009-08-10 | 2010-08-09 | Semi-crystalline, fast absorbing polymer formulation |
JP2012524770A JP5635095B2 (en) | 2009-08-10 | 2010-08-09 | Semi-crystalline fast absorbing polymer composition |
CA2770080A CA2770080C (en) | 2009-08-10 | 2010-08-09 | Semi-crystalline, fast absorbing polymer formulation |
RU2012108630/04A RU2542102C2 (en) | 2009-08-10 | 2010-08-09 | Semi-crystalline quickly resorbable polymer composition |
ES10744791T ES2732707T3 (en) | 2009-08-10 | 2010-08-09 | Quickly absorbed semi-crystalline polymer formulation |
MX2012001792A MX356887B (en) | 2009-08-10 | 2010-08-09 | Semi-crystalline, fast absorbing polymer formulation. |
IN1284DEN2012 IN2012DN01284A (en) | 2009-08-10 | 2010-08-09 | |
AU2010282745A AU2010282745B2 (en) | 2009-08-10 | 2010-08-09 | Semi-crystalline, fast absorbing polymer formulation |
BR112012003097-3A BR112012003097B1 (en) | 2009-08-10 | 2010-08-09 | COMPOSITION OF QUICK ABSORPTION COPOLIESTER AND MEDICAL DEVICE |
EP10744791.4A EP2464678B1 (en) | 2009-08-10 | 2010-08-09 | Semi-crystalline, fast absorbing polymer formulation |
Applications Claiming Priority (2)
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US12/538,259 US9200112B2 (en) | 2009-08-10 | 2009-08-10 | Semi-crystalline, fast absorbing polymer formulation |
US12/538,259 | 2009-08-10 |
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US (1) | US9200112B2 (en) |
EP (1) | EP2464678B1 (en) |
JP (1) | JP5635095B2 (en) |
CN (1) | CN102471468A (en) |
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US20140275467A1 (en) * | 2013-03-15 | 2014-09-18 | Ethicon, Inc. | Polylactone Polymers Prepared from Monol and Diol Polymerization Initiators Processing Two or More Carboxylic Acid Groups |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4048256A (en) | 1976-06-01 | 1977-09-13 | American Cyanamid Company | Normally-solid, bioabsorbable, hydrolyzable, polymeric reaction product |
US4095600A (en) | 1976-06-01 | 1978-06-20 | American Cyanamid Company | Normally-solid, bioabsorbable, hydrolyzable, polymeric reaction product |
US4122129A (en) | 1976-06-01 | 1978-10-24 | American Cyanamid Company | Normally-solid, bioabsorbable, hydrolyzable, polymeric reaction product |
US5644002A (en) | 1995-01-19 | 1997-07-01 | Ethicon, Inc. | Absorbable polyalkylene diglycolates |
US20060051398A1 (en) | 2004-09-03 | 2006-03-09 | Sasa Andjelic | Method of preventing post-operative surgical adhesion |
US20080103284A1 (en) | 2006-10-31 | 2008-05-01 | Sasa Andjelic | Absorbable copolyesters of poly(ethoxyethylene diglycolate) and glycolide |
US20080103285A1 (en) | 2006-10-31 | 2008-05-01 | Sasa Andjelic | Absorbable copolyesters of poly(ethoxyethylene diglycolate) and glycolide |
US20080243101A1 (en) * | 2004-09-03 | 2008-10-02 | Ethicon, Inc. | Absorbable polymer formulations |
Family Cites Families (45)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AT336197B (en) | 1972-11-03 | 1977-04-25 | Ethicon Inc | MULTI-THREAD SURGICAL SUTURE MATERIAL |
US3997512A (en) | 1973-11-21 | 1976-12-14 | American Cyanamid Company | High molecular weight polyester resin, the method of making the same |
AR205997A1 (en) | 1973-11-21 | 1976-06-23 | American Cyanamid Co | NORMALLY SOLID BIODEGRADABLE AND HYDROLYZABLE POLYESTER RESIN |
US4076798A (en) | 1975-05-29 | 1978-02-28 | American Cyanamid Company | High molecular weight polyester resin, the method of making the same and the use thereof as a pharmaceutical composition |
US4118470A (en) | 1976-06-01 | 1978-10-03 | American Cyanamid Company | Normally-solid, bioabsorbable, hydrolyzable, polymeric reaction product |
US4343788A (en) | 1979-06-29 | 1982-08-10 | The Procter & Gamble Company | Antimicrobial polymer compositions |
US4689424A (en) | 1981-08-06 | 1987-08-25 | Ethicon, Inc. | Radiation sterilizable absorbable polymeric materials and methods for manufacturing the same |
US4435590A (en) | 1981-08-06 | 1984-03-06 | Ethicon, Inc. | Radiation sterilizable absorbable polymeric materials and methods for manufacturing the same |
US4452973A (en) | 1982-11-12 | 1984-06-05 | American Cyanamid Company | Poly(glycolic acid)/poly(oxyethylene) triblock copolymers and method of manufacturing the same |
US4438253A (en) | 1982-11-12 | 1984-03-20 | American Cyanamid Company | Poly(glycolic acid)/poly(alkylene glycol) block copolymers and method of manufacturing the same |
US4938763B1 (en) | 1988-10-03 | 1995-07-04 | Atrix Lab Inc | Biodegradable in-situ forming implants and method of producing the same |
US6495656B1 (en) * | 1990-11-30 | 2002-12-17 | Eastman Chemical Company | Copolyesters and fibrous materials formed therefrom |
WO1994008078A1 (en) | 1992-10-02 | 1994-04-14 | Cargill, Incorporated | A melt-stable lactide polymer fabric and process for manufacture thereof |
JP3220331B2 (en) | 1993-07-20 | 2001-10-22 | エチコン・インコーポレーテツド | Absorbable liquid copolymers for parenteral administration |
US5442033A (en) | 1993-07-20 | 1995-08-15 | Ethicon, Inc. | Liquid copolymers of epsilon-caprolactone and lactide |
AU706434B2 (en) | 1994-10-18 | 1999-06-17 | Ethicon Inc. | Injectable liquid copolymers for soft tissue repair and augmentation |
US5599852A (en) | 1994-10-18 | 1997-02-04 | Ethicon, Inc. | Injectable microdispersions for soft tissue repair and augmentation |
US5688900A (en) | 1995-01-19 | 1997-11-18 | Ethicon, Inc. | Absorbable polyalkylene diglycolates |
US5464929A (en) | 1995-03-06 | 1995-11-07 | Ethicon, Inc. | Absorbable polyoxaesters |
US6403655B1 (en) | 1995-03-06 | 2002-06-11 | Ethicon, Inc. | Method of preventing adhesions with absorbable polyoxaesters |
US5618552A (en) | 1995-03-06 | 1997-04-08 | Ethicon, Inc. | Absorbable polyoxaesters |
US6147168A (en) | 1995-03-06 | 2000-11-14 | Ethicon, Inc. | Copolymers of absorbable polyoxaesters |
US5719256A (en) | 1995-10-19 | 1998-02-17 | Mitsu Toatsu Chemicals, Inc. | Process for preparing polycondensation polymer compound |
FR2764514B1 (en) | 1997-06-13 | 1999-09-03 | Biopharmex Holding Sa | IMPLANT INJECTED IN SUBCUTANEOUS OR INTRADERMAL WITH CONTROLLED BIORESORBABILITY FOR REPAIR OR PLASTIC SURGERY AND AESTHETIC DERMATOLOGY |
US6201072B1 (en) | 1997-10-03 | 2001-03-13 | Macromed, Inc. | Biodegradable low molecular weight triblock poly(lactide-co- glycolide) polyethylene glycol copolymers having reverse thermal gelation properties |
DE10004832A1 (en) | 2000-01-31 | 2001-08-16 | Ethicon Gmbh | Flat implant with X-ray visible elements |
US20040039441A1 (en) | 2002-05-20 | 2004-02-26 | Rowland Stephen Maxwell | Drug eluting implantable medical device |
DE10050199A1 (en) | 2000-10-11 | 2002-04-25 | Ethicon Gmbh | Areal implant having a flexible basic structure on a polymer basis, contains ultrasonically detectable elements, which contain or produce gas and set up for detectability for at least four weeks after implantation |
DE10123934A1 (en) | 2001-05-17 | 2002-12-05 | Ethicon Gmbh | Flat implant |
US6514517B2 (en) | 2001-06-20 | 2003-02-04 | Ethicon, Inc. | Antimicrobial coatings for medical devices |
EP2082724B1 (en) | 2001-11-15 | 2013-08-21 | Laboratorios Miret, S.A. | Use of cationic surfactant as antimicrobial activity enhancer in deodorants and oral care |
CA2500540A1 (en) | 2002-09-30 | 2004-04-15 | Bausch & Lomb Incorporated | Bacterial attachment reduction to biomaterials and biomedical devices |
US20040120981A1 (en) | 2002-12-20 | 2004-06-24 | Aruna Nathan | Crosslinked alkyd polyesters for medical applications |
US7381751B2 (en) | 2003-08-26 | 2008-06-03 | Shantha Sarangapani | Antimicrobial composition for medical articles |
US20060009839A1 (en) | 2004-07-12 | 2006-01-12 | Scimed Life Systems, Inc. | Composite vascular graft including bioactive agent coating and biodegradable sheath |
JP2008514050A (en) | 2004-09-14 | 2008-05-01 | コーニンクレッカ フィリップス エレクトロニクス エヌ ヴィ | Overvoltage protection device and radio frequency receiver and radio frequency identification tag having such a device |
US8263105B2 (en) | 2004-12-01 | 2012-09-11 | Tyco Healthcare Group Lp | Biomaterial drug delivery and surface modification compositions |
US9180229B2 (en) * | 2005-05-19 | 2015-11-10 | Ethicon, Inc. | Antimicrobial polymer compositions and the use thereof |
US20060263444A1 (en) | 2005-05-19 | 2006-11-23 | Xintian Ming | Antimicrobial composition |
US8840876B2 (en) | 2005-05-19 | 2014-09-23 | Ethicon, Inc. | Antimicrobial polymer compositions and the use thereof |
US20060264347A1 (en) | 2005-05-19 | 2006-11-23 | Xintian Ming | Antimicrobial composition |
DE102006020644A1 (en) | 2006-04-28 | 2007-10-31 | Bayer Innovation Gmbh | Silicone elastomer containing homogeneously dispersed, micronized antiseptic, e.g. chlorhexidine, octenidine or triclosan, used for the production of plastic medical articles, especially catheters |
US7968656B2 (en) | 2006-10-31 | 2011-06-28 | Ethicon, Inc. | Absorbable copolyesters of poly(ethoxyethylene diglycolate) and glycolide |
EP2098254A1 (en) | 2008-03-06 | 2009-09-09 | Bayer MaterialScience AG | Medical adhesives for surgery with bioactive compounds |
US9044524B2 (en) | 2009-10-30 | 2015-06-02 | Ethicon, Inc. | Absorbable polyethylene diglycolate copolymers to reduce microbial adhesion to medical devices and implants |
-
2009
- 2009-08-10 US US12/538,259 patent/US9200112B2/en active Active
-
2010
- 2010-08-09 ES ES10744791T patent/ES2732707T3/en active Active
- 2010-08-09 WO PCT/US2010/044836 patent/WO2011019631A1/en active Application Filing
- 2010-08-09 EP EP10744791.4A patent/EP2464678B1/en active Active
- 2010-08-09 IN IN1284DEN2012 patent/IN2012DN01284A/en unknown
- 2010-08-09 CN CN2010800362144A patent/CN102471468A/en active Pending
- 2010-08-09 BR BR112012003097-3A patent/BR112012003097B1/en not_active IP Right Cessation
- 2010-08-09 RU RU2012108630/04A patent/RU2542102C2/en not_active IP Right Cessation
- 2010-08-09 MX MX2012001792A patent/MX356887B/en active IP Right Grant
- 2010-08-09 CA CA2770080A patent/CA2770080C/en not_active Expired - Fee Related
- 2010-08-09 JP JP2012524770A patent/JP5635095B2/en not_active Expired - Fee Related
- 2010-08-09 AU AU2010282745A patent/AU2010282745B2/en not_active Ceased
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4048256A (en) | 1976-06-01 | 1977-09-13 | American Cyanamid Company | Normally-solid, bioabsorbable, hydrolyzable, polymeric reaction product |
US4095600A (en) | 1976-06-01 | 1978-06-20 | American Cyanamid Company | Normally-solid, bioabsorbable, hydrolyzable, polymeric reaction product |
US4122129A (en) | 1976-06-01 | 1978-10-24 | American Cyanamid Company | Normally-solid, bioabsorbable, hydrolyzable, polymeric reaction product |
US5644002A (en) | 1995-01-19 | 1997-07-01 | Ethicon, Inc. | Absorbable polyalkylene diglycolates |
US20060051398A1 (en) | 2004-09-03 | 2006-03-09 | Sasa Andjelic | Method of preventing post-operative surgical adhesion |
US20080243101A1 (en) * | 2004-09-03 | 2008-10-02 | Ethicon, Inc. | Absorbable polymer formulations |
US20080103284A1 (en) | 2006-10-31 | 2008-05-01 | Sasa Andjelic | Absorbable copolyesters of poly(ethoxyethylene diglycolate) and glycolide |
US20080103285A1 (en) | 2006-10-31 | 2008-05-01 | Sasa Andjelic | Absorbable copolyesters of poly(ethoxyethylene diglycolate) and glycolide |
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BR112012003097B1 (en) | 2019-07-16 |
MX2012001792A (en) | 2012-03-16 |
BR112012003097A2 (en) | 2016-02-23 |
CA2770080A1 (en) | 2011-02-17 |
MX356887B (en) | 2018-06-18 |
JP2013501849A (en) | 2013-01-17 |
CN102471468A (en) | 2012-05-23 |
RU2012108630A (en) | 2013-09-20 |
AU2010282745B2 (en) | 2015-02-05 |
RU2542102C2 (en) | 2015-02-20 |
AU2010282745A1 (en) | 2012-03-15 |
EP2464678B1 (en) | 2019-05-01 |
US20110034567A1 (en) | 2011-02-10 |
US9200112B2 (en) | 2015-12-01 |
IN2012DN01284A (en) | 2015-05-15 |
JP5635095B2 (en) | 2014-12-03 |
ES2732707T3 (en) | 2019-11-25 |
CA2770080C (en) | 2018-11-13 |
EP2464678A1 (en) | 2012-06-20 |
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