CA2079275A1 - Blends of glycolide and/or lactide polymers and poly(p-dioxanone) homopolymers and copolymers and absorbable surgical devices made therefrom - Google Patents
Blends of glycolide and/or lactide polymers and poly(p-dioxanone) homopolymers and copolymers and absorbable surgical devices made therefromInfo
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- glycolide
- lactide
- dioxanone
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Abstract
ABSTRACT OF THE DISCLOSURE
Polymer blends of glycolide homopolymer, lactide homopolymer and/or glycolide/lactide copolymer and poly(p-dioxanone) and/or copolymers of p-dioxanone and glycolide and/or lactide and absorbable surgical devices manufactured therefrom having improved mechanical properties, such as improved impact and cyclic flex, are disclosed.
Polymer blends of glycolide homopolymer, lactide homopolymer and/or glycolide/lactide copolymer and poly(p-dioxanone) and/or copolymers of p-dioxanone and glycolide and/or lactide and absorbable surgical devices manufactured therefrom having improved mechanical properties, such as improved impact and cyclic flex, are disclosed.
Description
2 0 7 ~ 2 7 ~
203-~42 (1228) POLY~P-DIOXANONE) HOMOPOLYMERS AND COPOLYMERS AND
CROSS REFERENCE TO RELATED APPLICATION
BACKGROUND OF THE INVENTION
This invention relates to glycolide and/or laetide based polymer eompositions and more particularly to polymer eompositions whieh are a blend of a glycolide and/or laetide homopolymer or eopolymer and poly(p-dioxanone) homopolymer and/or p-dioxanone eopolymers, said polymer compositions being particularly useful in the manufaeture of absorbable surgical deviees.
Polymers and eopolymers of, and surgical deviees made from, laetide and/or glycolide and/or related compounds are well-known. See, e.g., U.S. Patent Nos. 2,668,162, 2,683,136, 2,703,316, 2,758,987, 3,225,766, 3,268,486, 3,268,487, 3,297,033, 3,422,181, 3,442,871, 3,463,158, 20 3,468,853, 3,531,561, 3,565,869, 3,597,449, 3,620,218, 3,626,948, 3,636,956, 3,736,646, 3,739,773, 3,772,420, 3,773,919, 3,781,349, 3,784,585, 3,792,010, 3,797,499, 3,839,297, 3,846,382, 3,867,190, 3,875,937, 3,878,284, 3,896,802, 3,902,497, 3,937,223, 3,982,543, 4,033,938, 25 4,045,418, 4,057,537, 4,060,089, 4,137,921, 4,157,437, 4,243,775, 4,246,904, 4,273,920, 4,275,813, 4,279,249, 4,300,565, and 4,744,365, U.K. Pat. or Appln. Nos. 779,291, 1,332,505, 1,414,600, and 2,102,827, D.K. Gilding et al., "Biodegradable polymers for use in surgery-polyglycolic/poly (lactic acid) homo-and copolymers: 1," Polymer, Volume 20, 2~79275 1 pages 1459-1464 (1979), and D.F. Williams (ed.), BiocompatibilitY of Clinical Implant Materials, Volume II, chapter 9: "Riodegradable Polymers" (19gl). All of the foregoing documents are hereby incorporated by reference.
It is known that annealing polymers, copolymers, and surgical devices made from lactide and/or glycolide and/or related compounds increases the crystallinity and in vivo tensile strength retention of the polymers, copolymers, and surgical devices. It is also known that the greater the crystallinity/ the longer such polymers, copolymers, and surgical devices retain their in vivo tensile strength.
See, e.g., U.S. Patent Nos. 3,636,956, 4,137,921, U.K.
Appln. No. 2,102,827, and Williams. It is also known that increasing the crystallinity of such polymers and copolymers makes them more brittle and, thus, decreases their utility as injection molded surgical devices.
In U.S. Patent No. 4,744,365 it was found that certain two-phase compositions derived from lactide and glycolide in which lactide moieties predominate, have a remarkable and unexpected balance of desirable properties.
Those properties include lack of brittleness and the ability to be injection molded and annealed. The properties of the composition make it possible to injection mold surgical devices (e.g., staples, clips) from the composition and to anneal those devices to obtain devices having a remar~able and unexpected balance of desirable properties~ As compared to a substantially amorphous, one-phase poly(lactide/glycolide) device of a given composition, the annealed, two-phase device of the same overall composition has a much higher distortion temperature but essentially the same in vivo rate of loss of tensile strength. Thus, the compositions of U.S.
2~79275 1 Patent No. 9,744,365 make it possible to increase the resistance to thermal distortion of poly(lactide/glycolide) surgical devices without adversely affecting their rate of loss of tensile strength. More particularly, the compositions of U.S. Patent No. 4,744,365 comprise a multi-phase polymeric composition derived from lactide and glycolide, the first phase having about 0 to about 25% m glycolide moieties and about 75 to about 100~ m lactide moieties and the other phases having glycolide and laetide moieties in amounts such that the composition overall has up to 45% m glycolide moieties, wherein the first phase constitutes at least 50% (and preferably ~ot more than about 95~) by weight of the eomposition.
In addition to the afore-recited patents and other documents which disclose polymers and copolymers of, and surgical devices made from lactide and glycolide, other documents disclose surgical devices prepared from copolymers of glycolide and other monomers, such as p-dioxanone and from blends of lactide and/or glycolide and other polymers.
For example, U.S. Patent No. 4,643,191 discloses crystalline copolymers of p-dioxanone and lactide and surgical devices made therefrom. U.S. Patent No. 4,653,497 discloses the preparation of crystalline copolymers derived from glycolide and p-dioxanone and surgical devices made therefrom said to have a desirable combination of good strength, fast absorption and excellent pliability (as exhibited by Young's modulus). U.S. Patent No. 5,007,923 discloses a crystalline copolyester of p-dioxanone and a prepolymer of lactide and glycolide, and surgical filaments derived therefrom. U.S.
Patent No. 4,428,376 discloses the preparation of surgical staples from homopolymers and copolymers of lactide, glycolide and p-dioxanone. U.S. Patent No. 4,201,216 discloses sutures, as well as film formers (coatings) for said sutures, derived from homopolymers and copolymers of lactide and glycolide, i.e. polylactide, polyglycolide, and copolymers of lactide and glycolide with each other and with other reactive monomers, e.g., poly(p-dioxanone) and the like. U.S. Patent No. 4,591,630 discloses thermally formed annealed surgical devices made from unoriented polymers and copolymers of p-dioxanone. U.S. Patent No. 4,559,945 discloses the preparation of crystalline copolyesters produced by reacting either lactide, glycolide, p-dioxanone or mixtures thereof with a poly(alkylene malonate) polyester and surgical devices made therefrom.
More recently, U.S. Patent No. 4,646,741 discloses surgical fasteners derived from a blend of a lactide/glycolide copolymer and poly(p-dioxanone). In particular, the blends of said U.S. Patent No. 4,646,741 are disclosed to comprise (a) a copolymer containing from about 65 to about 90 mole percent lactide and from about 10 to about 35 mole percent glycolide and (b) from about 25 to about 50 weight percent poly(p-dioxanone). The patentee states that with respect to the proportion of poly(p-dioxanone) in the blend, if the proportion were too high the fastener would have ir~adequate stiffness and if it were too low the dimensional stability upon exposure to elevated temperature would be inade~uate.
It is further stated that the principal advantages that are obtained by the addition of poly(p-dioxanone) to the copolymer, i.e. glycolide/lactide, are improved heat resistance so that the dimensional change upon exposure to moderately elevated temperature (e.g. 120 to 185-F) is less apt to occur and slightly reduced absorption time upon 2~79275 1 implantation in the body, while still maintaining acceptable breaking strength retention after implantation. The fasteners derived from these prior art blends are made by injection molding the blends at temper~tures in the range of from about 130 to about 140-C. The patentee states that after molding, the fasteners are preferably annealed to impart dimensional stability (at elevated temperature) via crystallization.
It is one object of the present invention to provide novel polymer compositions useful for the manufacture of surgical devices.
It is another object of this invention to provlde polymer compositions which are comprised of novel blends of two or more polymers.
It is still another object of the present invention to provide absorbable surgical devices having improved mechanical properties which are manufactured from the novel polymer compositions of this invention.
A still further object of this invention is to provide absorbable surgical devices, derived from the novel polymer compositions of the present invention, which exhibit improved impact resistance, improved cvclic flex performance, improved resistance to crazing and other improved physical properties.
These and other objects are accomplished herein by providing an absorbable polymeric composition, suitable for manufacture of surgical devices, comprising a blend of:
(a) a polymer selected from the group consisting of glycolide homopolymer, lactide homopolymer, a blend of ~97927~
1 glycolide ho~opolymer and lactide hom~polymer, a glycolide~lactide copolymer and mixtures thereof; and (b) from about 1 to no more than about 20 ~-eight percent poly(p-dioxanone) or a copolymer of p-dioxanone and glycolide and/or lactide wherein p-dioxanone comprises the predominant monomer, based on the total weight of the blend.
Other objects of the invention are achieved herein by providing absorbable surgical devices derived from the afore-described polymer blend compositions of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the present invention, it has been found that the addition of a relatively minor amount, i.e. up to 20 wt. %, of poly(p-dioxanone) homopolymer or copolymer of p-dioxanone and glycolide and/or lactide, wherein p-dioxanone comprises the predominant monomer, to glycolide and/or lactide homopolymer or copolymer improves the physical and mechanical properties of absorbable surgical devices derived therefrom in comparison with surgical devices derived from the glycolide and/or lactide polymers or copolymers alone. More particularly, and in accordance with the present invention, surgical devices prepared from polymer blends comprising glycolide and/or lactide homopolymer or copolymer and amounts of poly(p-dioxanone) or copolymers of p-dioxanone as defined hereinabove up to and including 20 wt.% are found to exhibit improved impact resistance, improved crazing resistance and improved cyclic flexibility.
The polymer compositions of the present in~ention are blends of at least two polymers one of which is 2~7~27~
1 predominantly (p-dioxanone), i.e., greater than about 50 mole percent and preferabl~ at least ~0 mole percent. More particularly, the novel blends of the present invention comprise a p-dioxanone polymer and a polymer selected from a glycolide homopolymer, a lactide homopolymer, a blend of a glycolide homopolymer and a lactide homopolymer, a glycolide/lactide copolymer or mixtures of the foregoing.
Preferred polymer compositions encompassed by the present invention include blends comprised of glycolide/lactide copolymer and up to 20 wt.% of poly(p-dioxanone) homopolymer or a copolymer of at least 80 mole percent p-dioxanone and glycolide and/or lactide.
When glycolide and lactide are present in the blends of the present invention, e.g. when a mixture of glycolide homopolymer and lactide homopolymer or glycolide/lactide copolymer are employed, the proportion of each in the composition in relation to each other can vary depending upon the physical properties desired. For example, if the proportion of lactide is too high, the absorption time of a surgical implant device derived therefrom may be too long and if the glycolide proportion is too high, the breaking strength (tensile strength) retention upon implantation in the body of the device may be unacceptable. In general, however, acceptable results are achieved when up to about 50~ glycolide, in relation to the amount of lactide, is used. Thus, preferred glycolide/lactide copolymers useful in the practice of the present invention are those, for example, comprising about 18/82 glycolide/lactide (mole percent), 10/90 glycolide/lactide (mole percent), 35/65 glycolide/lactide (mole percent) and 42/58 glycolide/lactide (mole percent).
2~7927~
1 The glycolide homopol~mers, lactide homopolymers and glycolide~lactide copolymers employed in the blends of the present invention are known materials and are readily synthesized by known methods. Generally, the glycolide and/or lactide homopolymers and glycolide/lactide copolymers used in the practice of the present invention have a molecular weight such that they have an inherent viscosity of from about 0.9 to about 2.0 dl/g and preferably about 1.0 to about 1.8 dl/g measured at 30~C at a concentration of 0.25 g/dl in chloroform or hexafluoroisopropanol (HFIP).
Particularly preferred glycolide/lactide copolymers useful for the purposes of the present invention are the two-phase or multi-phase compositions disclosed in afore-discussed U.S. Patent No. 4,744,365, the entire contents of which are incorporated by reference herein.
The poly(p-dioxanone) homopolymer employed in polymer blends of the present invention is also a well known material. For the purposes of the present invention, poly(p-dioxanone) having an inherent viscosity of from about 0.4 to about 1.8 and preferably about 0.8 dl/g measured at 30~C at a concentration of 0.25 g/dl in chloroform or HFIP
is generally employed.
Copolymers of p-dioxanone and glycolide and/or lactide may be formed by known procedures. The p-dioxanone is the predominant monomer in such copolymers and typically comprises at least 80 mole percent, preferably at least 90 mole percent. Copolymerization of p-dioxanone with glycolide and/or lactide has been found to facilitate handling of the p-dioxanone component, e.g., processing through and removal from extrusion equipment. The inherent viscosity of such copolymers is typically from 0.4 to about 2 0 7 ~ 2 7 ~
1 1.8 measured at 30C at a concentration of 0.25 g/dl in chloroform or HFIP.
The polymer blends of the present invention are typically prepared by melt blending the components of the blend. The glycolide and/or lactide homopolymer or mixture thereof and/or the glycolide/lactide copolymer is employed in the blend in a major amount, that is, from about 80 to about 99 weight percent of the total weight of the blend, the remainder, i.e. from about 1 to about 20 weight percent, comprising poly(p-dioxanone). Preferred blends herein comprise from about 5 to 20 weight percent poly(p-dioxanone) or a copolymer of p-dioxanone and glycolide and/or lactide.
Melt blending is typically carried out at a temperature of 170~C to 200~C for a time sufficient to liquify the components, the time being dependent on such parameters as vessel, heat transfer properties, presence and extent of bleeding. Typically, melt time ranges from a few minutes for small amounts of polymer to a couple of hours for large quantities.
It has also been found herein that surgical devices manufactured from the blends of the present invention possess the excellent afore-described physical properties whether or not annealed. For example, unannealed surgical devices prepared from blends comprising 18/82 glycolide/lactide and 15 to 20% polydioxanone are found to possess sufficient rigidity to penetrate tissue, exhibit advantageous impact resistance, and possess excellent cyclic flex performance.
Whichever polymer blend of the present invention is used, the absorbable surgical devices are made preferably by injection molding the blend at temperatures in the range 207~7~
1 of from about 300 to about 400-F at an injection molding pressure of, for example, about 1500 psi. Typically, the feed for the injection molding apparatus is a melt blend of the two polymers in pellet form. The polymers should be quite dry when being injection molded in order to avoid hydrolytic degradation during processing. After molding, the surgical devices can be packaged and sterilized by conventional procedures. It may be desirable to anneal the devices to remove residual stresses and strains, to stabilize the shape of the device, and to reduce or eliminate defects in the piece. Annealing typically comprises reheating the polymeric device to above its glass transition temperature where chain mobility is greatest, and then slowly and gradually cooling the device to avoid reintroducing any stresses and strains. Procedures, conditions and apparatus for annealing polymeric structures are well known in the art. A wide variety of ahsorbable surgical devices can be manufactured from the polymer blends of the present invention. These include fasteners, such as staples, clips and the like and other implant devices, such as pins, bone screws, and the like devices.
As expressed hereinbefore, the surgical devices of the present invention exhibit excellent in vivo cyclic flex performance, a mechanical property which is highly desired in surgical devices particularly, fvr example, in surgical implant devices, such as surgical fastener/retainer systems which, after implantation, are subject to a variety of forces and often undergo repeated flexing.
Furthermore, surgical devices manufactured from the novel polymer blends of the present invention exhibit improved impact resistance as well as improved crazing 2 ~ 7 9 2 7 3 1 resistance. Crazing may be defined as surface cracking of the material as contrasted with impact resistance which is more a measure of a material's tendency to allow crack propagation. Crazing may be observed visually, such as for example, a polymeric article which is flexed will evidence crazing by fogging of an otherwise clear or transparent material. In surgical applications, once a surgical article crazes, ~lthough the article may continue to function for a limited period, the article may not exhibit the desired strength. Thus, a material with a more limited tendency to craze when fabricated, for example, into a surgical implant device such as a bone screw, would permit the bone screw to be torqued to a greater extent without a likelihood that the screw would craze and thereby become ineffective for its intended purpose.
The examples below are illustrative of the blends of the present invention and surgical devices derived therefrom.
1 ~--.
2~79~7~
1 E~ample l A copolymer of qlycolide and lactide is prepared as follows:
Hydroxyacetic acid (glycolic acid) is heated under nitrogen to 180C to remove impurities such as water.
Pressure is then reduced and heating is continued for two hours to yield a prepolymer of polyglycolic acid, which is recovered and powdered.
The prepolymer is heated in the presence of Sb203 at 275C under low pressure with an ar~or. pur~e and stirring. The prepolymer cracks and glycolide is distilled over and recovered in a cold vacuum receiver. Preferably, the glycolide is purified by conventional techniques, such as distillation, crystallization, and sublimation.
L-lactide is used alone or in combination with a small amount of the DL racemer. L-lactide is purified by crystallization from toluene solution. The DL racemer, if used, is purified by crystallization from ethyl acetate.
A mixture of the purified glycolide (18 mole percent) and lactide (82 mole percent) is charged to a reactor under an argon blanket. A solution of stannous octoate catalyst in diethyl ether is added to give 0.02% w.
of catalyst, based on the total weight of glycolide and lactide. The reactor is further purged with argon and held at 5 psi while heating to 170-175C. Pressure and temperature are maintained for six hours.
The reaction product is isolated, co~minuted, and treated to remove residual reactants. Any method capable of removing the unreacted monomers from the crude reaction product may be used. A preferred purification procedure is as follows.
2~7q27~
1 After comminution, the crude reaction product is contacted with ethyl ether for about 72 hours in a Soxhlet-type extractor to remove unreacted monomer. Typically, 4-10% of the starting monomers remain unreacted, and the glass transition temperature of the crude copolymer is approximately 50C. Removal of unreacted monomers raises the glass transition temperature. As ~ill be understood by one skilled in the art, the composition of the copolymer may differ slightly from the composition of the starting monomeric mixture because the lactide and glycolide are not of equal reactivity.
After the extraction period, the partially purified copolymer is slowly heated under vacuum from ambient temperature to 140-C over a period of about 48 hours. The slow rate of heating is desirable to prevent melting (strictly speaking, flowing together) of the co-polymer particles and to remove any water present.
Desirably, dry inert gas is used to purge the system, and occasionally the heating step may require more than 48 hours to reach the desired glass transition temperature. The combination of slow heating and purging with dry gas removes any residual solvent (ethyl ether) present, thereby raising the glass transition temperature.
After removal of unreacted monomers (and of solvent, if solvent extraction is used), the purified copolymer is further dried if it was not dried enough in the monomer removal step and, in any event, stored to keep it dry.
Commercially available poly(p-dioxanone) is used to prepare the polymeric blend of the invention.
Alternatively, poly(p-dioxanone) is prepared according to 2~79275 1 the procedure described in U.S. Patent No. 4,052,488 to Doddi et al.
A melt blend of the glycolide,/lactide copolymer and poly(p-dioxanone) is prepared using an extruder having a mixing head operating at a melt temperature of about 170'C
to 200C. The glycolide/lactide copolymer and polySp-dioxanone) are combined in mole ratios of 80:20 and 85:15, melt blended and the resulting polymeric blends are pelletized for subsequent use as described hereinbelow.
2~7~7~
1 Example 2 The pelletized polymeric blends of Example 1 are injection molded at a temperature of 130C to 140-C at an injection molding pressure, e.g., 1,500 to 1,750 psi, to form a series of test plates measuring 2.2 inch x. 2.7 inch x 0.070 inch. Control test plates are also injection molded from the glycolide/lactide copolymer described in Example 1, none of which are annealed. One portion of the test plates are annealed at an annealing temperature of about 85 C to lOO'C for 12 to 16 hours to remove internal stresses. A
second portion of the test plates are not annealed. Control test plates are also injection molded from the glycolide/lactide copolymer described in Example 1, none of which are annealed.
2 ~ 7 9 2 7 ~
1 Example 3 The test plates injection molded as described in Example 2 are tested for impact resistance using a standard falling dart impact tester. The test plates are designated as follows:
Control: glycolide/lactide copolymer (18/82);
unannealed Sample 1: glycolid~/lactide copolymer (18/82) blended with poly(p-dioxanone) at a weight ratio of 85:15; unannealed Sample 2: glycolide/lactide copolymer (18/82) blended with poly(p-dioxanone) at a weight ratio of 85:15; annealed Sample 3: glycolide/lactide copolymer (18/82) blended with poly(p-dioxanone3 at a weight ratio of 80:20; unannealed Sample 4: glycolide/lactide copoiymer (18/82) blended with poly(p-dioxanone) at a weight ratio of 80:20; annealed The results of the impact tests are set forth in the following Table.
TABLE
Force (in-lb) Control ¦Sample 1 ¦Sample 2 Sample 3 Sample 4 __ Mode of Failure: 1. No effect; 2. Slight fractures;
3. Indentation with some crazing;
4. Cracks at point of contact; 5. Hole punched at point of contact; 6. Shattered.
2079~75 1 These results show that the pol~eric blends of the present invention exhibit improved impact resistance as compared to a non-blended control, i.e., a glycolide/lactide copolymer without added poly(p-dioxanone). In addition, the test plates for Samples 1-4 exhibit improved resistance to crazing. Improved cyclic flex performance is also to be expected.
203-~42 (1228) POLY~P-DIOXANONE) HOMOPOLYMERS AND COPOLYMERS AND
CROSS REFERENCE TO RELATED APPLICATION
BACKGROUND OF THE INVENTION
This invention relates to glycolide and/or laetide based polymer eompositions and more particularly to polymer eompositions whieh are a blend of a glycolide and/or laetide homopolymer or eopolymer and poly(p-dioxanone) homopolymer and/or p-dioxanone eopolymers, said polymer compositions being particularly useful in the manufaeture of absorbable surgical deviees.
Polymers and eopolymers of, and surgical deviees made from, laetide and/or glycolide and/or related compounds are well-known. See, e.g., U.S. Patent Nos. 2,668,162, 2,683,136, 2,703,316, 2,758,987, 3,225,766, 3,268,486, 3,268,487, 3,297,033, 3,422,181, 3,442,871, 3,463,158, 20 3,468,853, 3,531,561, 3,565,869, 3,597,449, 3,620,218, 3,626,948, 3,636,956, 3,736,646, 3,739,773, 3,772,420, 3,773,919, 3,781,349, 3,784,585, 3,792,010, 3,797,499, 3,839,297, 3,846,382, 3,867,190, 3,875,937, 3,878,284, 3,896,802, 3,902,497, 3,937,223, 3,982,543, 4,033,938, 25 4,045,418, 4,057,537, 4,060,089, 4,137,921, 4,157,437, 4,243,775, 4,246,904, 4,273,920, 4,275,813, 4,279,249, 4,300,565, and 4,744,365, U.K. Pat. or Appln. Nos. 779,291, 1,332,505, 1,414,600, and 2,102,827, D.K. Gilding et al., "Biodegradable polymers for use in surgery-polyglycolic/poly (lactic acid) homo-and copolymers: 1," Polymer, Volume 20, 2~79275 1 pages 1459-1464 (1979), and D.F. Williams (ed.), BiocompatibilitY of Clinical Implant Materials, Volume II, chapter 9: "Riodegradable Polymers" (19gl). All of the foregoing documents are hereby incorporated by reference.
It is known that annealing polymers, copolymers, and surgical devices made from lactide and/or glycolide and/or related compounds increases the crystallinity and in vivo tensile strength retention of the polymers, copolymers, and surgical devices. It is also known that the greater the crystallinity/ the longer such polymers, copolymers, and surgical devices retain their in vivo tensile strength.
See, e.g., U.S. Patent Nos. 3,636,956, 4,137,921, U.K.
Appln. No. 2,102,827, and Williams. It is also known that increasing the crystallinity of such polymers and copolymers makes them more brittle and, thus, decreases their utility as injection molded surgical devices.
In U.S. Patent No. 4,744,365 it was found that certain two-phase compositions derived from lactide and glycolide in which lactide moieties predominate, have a remarkable and unexpected balance of desirable properties.
Those properties include lack of brittleness and the ability to be injection molded and annealed. The properties of the composition make it possible to injection mold surgical devices (e.g., staples, clips) from the composition and to anneal those devices to obtain devices having a remar~able and unexpected balance of desirable properties~ As compared to a substantially amorphous, one-phase poly(lactide/glycolide) device of a given composition, the annealed, two-phase device of the same overall composition has a much higher distortion temperature but essentially the same in vivo rate of loss of tensile strength. Thus, the compositions of U.S.
2~79275 1 Patent No. 9,744,365 make it possible to increase the resistance to thermal distortion of poly(lactide/glycolide) surgical devices without adversely affecting their rate of loss of tensile strength. More particularly, the compositions of U.S. Patent No. 4,744,365 comprise a multi-phase polymeric composition derived from lactide and glycolide, the first phase having about 0 to about 25% m glycolide moieties and about 75 to about 100~ m lactide moieties and the other phases having glycolide and laetide moieties in amounts such that the composition overall has up to 45% m glycolide moieties, wherein the first phase constitutes at least 50% (and preferably ~ot more than about 95~) by weight of the eomposition.
In addition to the afore-recited patents and other documents which disclose polymers and copolymers of, and surgical devices made from lactide and glycolide, other documents disclose surgical devices prepared from copolymers of glycolide and other monomers, such as p-dioxanone and from blends of lactide and/or glycolide and other polymers.
For example, U.S. Patent No. 4,643,191 discloses crystalline copolymers of p-dioxanone and lactide and surgical devices made therefrom. U.S. Patent No. 4,653,497 discloses the preparation of crystalline copolymers derived from glycolide and p-dioxanone and surgical devices made therefrom said to have a desirable combination of good strength, fast absorption and excellent pliability (as exhibited by Young's modulus). U.S. Patent No. 5,007,923 discloses a crystalline copolyester of p-dioxanone and a prepolymer of lactide and glycolide, and surgical filaments derived therefrom. U.S.
Patent No. 4,428,376 discloses the preparation of surgical staples from homopolymers and copolymers of lactide, glycolide and p-dioxanone. U.S. Patent No. 4,201,216 discloses sutures, as well as film formers (coatings) for said sutures, derived from homopolymers and copolymers of lactide and glycolide, i.e. polylactide, polyglycolide, and copolymers of lactide and glycolide with each other and with other reactive monomers, e.g., poly(p-dioxanone) and the like. U.S. Patent No. 4,591,630 discloses thermally formed annealed surgical devices made from unoriented polymers and copolymers of p-dioxanone. U.S. Patent No. 4,559,945 discloses the preparation of crystalline copolyesters produced by reacting either lactide, glycolide, p-dioxanone or mixtures thereof with a poly(alkylene malonate) polyester and surgical devices made therefrom.
More recently, U.S. Patent No. 4,646,741 discloses surgical fasteners derived from a blend of a lactide/glycolide copolymer and poly(p-dioxanone). In particular, the blends of said U.S. Patent No. 4,646,741 are disclosed to comprise (a) a copolymer containing from about 65 to about 90 mole percent lactide and from about 10 to about 35 mole percent glycolide and (b) from about 25 to about 50 weight percent poly(p-dioxanone). The patentee states that with respect to the proportion of poly(p-dioxanone) in the blend, if the proportion were too high the fastener would have ir~adequate stiffness and if it were too low the dimensional stability upon exposure to elevated temperature would be inade~uate.
It is further stated that the principal advantages that are obtained by the addition of poly(p-dioxanone) to the copolymer, i.e. glycolide/lactide, are improved heat resistance so that the dimensional change upon exposure to moderately elevated temperature (e.g. 120 to 185-F) is less apt to occur and slightly reduced absorption time upon 2~79275 1 implantation in the body, while still maintaining acceptable breaking strength retention after implantation. The fasteners derived from these prior art blends are made by injection molding the blends at temper~tures in the range of from about 130 to about 140-C. The patentee states that after molding, the fasteners are preferably annealed to impart dimensional stability (at elevated temperature) via crystallization.
It is one object of the present invention to provide novel polymer compositions useful for the manufacture of surgical devices.
It is another object of this invention to provlde polymer compositions which are comprised of novel blends of two or more polymers.
It is still another object of the present invention to provide absorbable surgical devices having improved mechanical properties which are manufactured from the novel polymer compositions of this invention.
A still further object of this invention is to provide absorbable surgical devices, derived from the novel polymer compositions of the present invention, which exhibit improved impact resistance, improved cvclic flex performance, improved resistance to crazing and other improved physical properties.
These and other objects are accomplished herein by providing an absorbable polymeric composition, suitable for manufacture of surgical devices, comprising a blend of:
(a) a polymer selected from the group consisting of glycolide homopolymer, lactide homopolymer, a blend of ~97927~
1 glycolide ho~opolymer and lactide hom~polymer, a glycolide~lactide copolymer and mixtures thereof; and (b) from about 1 to no more than about 20 ~-eight percent poly(p-dioxanone) or a copolymer of p-dioxanone and glycolide and/or lactide wherein p-dioxanone comprises the predominant monomer, based on the total weight of the blend.
Other objects of the invention are achieved herein by providing absorbable surgical devices derived from the afore-described polymer blend compositions of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the present invention, it has been found that the addition of a relatively minor amount, i.e. up to 20 wt. %, of poly(p-dioxanone) homopolymer or copolymer of p-dioxanone and glycolide and/or lactide, wherein p-dioxanone comprises the predominant monomer, to glycolide and/or lactide homopolymer or copolymer improves the physical and mechanical properties of absorbable surgical devices derived therefrom in comparison with surgical devices derived from the glycolide and/or lactide polymers or copolymers alone. More particularly, and in accordance with the present invention, surgical devices prepared from polymer blends comprising glycolide and/or lactide homopolymer or copolymer and amounts of poly(p-dioxanone) or copolymers of p-dioxanone as defined hereinabove up to and including 20 wt.% are found to exhibit improved impact resistance, improved crazing resistance and improved cyclic flexibility.
The polymer compositions of the present in~ention are blends of at least two polymers one of which is 2~7~27~
1 predominantly (p-dioxanone), i.e., greater than about 50 mole percent and preferabl~ at least ~0 mole percent. More particularly, the novel blends of the present invention comprise a p-dioxanone polymer and a polymer selected from a glycolide homopolymer, a lactide homopolymer, a blend of a glycolide homopolymer and a lactide homopolymer, a glycolide/lactide copolymer or mixtures of the foregoing.
Preferred polymer compositions encompassed by the present invention include blends comprised of glycolide/lactide copolymer and up to 20 wt.% of poly(p-dioxanone) homopolymer or a copolymer of at least 80 mole percent p-dioxanone and glycolide and/or lactide.
When glycolide and lactide are present in the blends of the present invention, e.g. when a mixture of glycolide homopolymer and lactide homopolymer or glycolide/lactide copolymer are employed, the proportion of each in the composition in relation to each other can vary depending upon the physical properties desired. For example, if the proportion of lactide is too high, the absorption time of a surgical implant device derived therefrom may be too long and if the glycolide proportion is too high, the breaking strength (tensile strength) retention upon implantation in the body of the device may be unacceptable. In general, however, acceptable results are achieved when up to about 50~ glycolide, in relation to the amount of lactide, is used. Thus, preferred glycolide/lactide copolymers useful in the practice of the present invention are those, for example, comprising about 18/82 glycolide/lactide (mole percent), 10/90 glycolide/lactide (mole percent), 35/65 glycolide/lactide (mole percent) and 42/58 glycolide/lactide (mole percent).
2~7927~
1 The glycolide homopol~mers, lactide homopolymers and glycolide~lactide copolymers employed in the blends of the present invention are known materials and are readily synthesized by known methods. Generally, the glycolide and/or lactide homopolymers and glycolide/lactide copolymers used in the practice of the present invention have a molecular weight such that they have an inherent viscosity of from about 0.9 to about 2.0 dl/g and preferably about 1.0 to about 1.8 dl/g measured at 30~C at a concentration of 0.25 g/dl in chloroform or hexafluoroisopropanol (HFIP).
Particularly preferred glycolide/lactide copolymers useful for the purposes of the present invention are the two-phase or multi-phase compositions disclosed in afore-discussed U.S. Patent No. 4,744,365, the entire contents of which are incorporated by reference herein.
The poly(p-dioxanone) homopolymer employed in polymer blends of the present invention is also a well known material. For the purposes of the present invention, poly(p-dioxanone) having an inherent viscosity of from about 0.4 to about 1.8 and preferably about 0.8 dl/g measured at 30~C at a concentration of 0.25 g/dl in chloroform or HFIP
is generally employed.
Copolymers of p-dioxanone and glycolide and/or lactide may be formed by known procedures. The p-dioxanone is the predominant monomer in such copolymers and typically comprises at least 80 mole percent, preferably at least 90 mole percent. Copolymerization of p-dioxanone with glycolide and/or lactide has been found to facilitate handling of the p-dioxanone component, e.g., processing through and removal from extrusion equipment. The inherent viscosity of such copolymers is typically from 0.4 to about 2 0 7 ~ 2 7 ~
1 1.8 measured at 30C at a concentration of 0.25 g/dl in chloroform or HFIP.
The polymer blends of the present invention are typically prepared by melt blending the components of the blend. The glycolide and/or lactide homopolymer or mixture thereof and/or the glycolide/lactide copolymer is employed in the blend in a major amount, that is, from about 80 to about 99 weight percent of the total weight of the blend, the remainder, i.e. from about 1 to about 20 weight percent, comprising poly(p-dioxanone). Preferred blends herein comprise from about 5 to 20 weight percent poly(p-dioxanone) or a copolymer of p-dioxanone and glycolide and/or lactide.
Melt blending is typically carried out at a temperature of 170~C to 200~C for a time sufficient to liquify the components, the time being dependent on such parameters as vessel, heat transfer properties, presence and extent of bleeding. Typically, melt time ranges from a few minutes for small amounts of polymer to a couple of hours for large quantities.
It has also been found herein that surgical devices manufactured from the blends of the present invention possess the excellent afore-described physical properties whether or not annealed. For example, unannealed surgical devices prepared from blends comprising 18/82 glycolide/lactide and 15 to 20% polydioxanone are found to possess sufficient rigidity to penetrate tissue, exhibit advantageous impact resistance, and possess excellent cyclic flex performance.
Whichever polymer blend of the present invention is used, the absorbable surgical devices are made preferably by injection molding the blend at temperatures in the range 207~7~
1 of from about 300 to about 400-F at an injection molding pressure of, for example, about 1500 psi. Typically, the feed for the injection molding apparatus is a melt blend of the two polymers in pellet form. The polymers should be quite dry when being injection molded in order to avoid hydrolytic degradation during processing. After molding, the surgical devices can be packaged and sterilized by conventional procedures. It may be desirable to anneal the devices to remove residual stresses and strains, to stabilize the shape of the device, and to reduce or eliminate defects in the piece. Annealing typically comprises reheating the polymeric device to above its glass transition temperature where chain mobility is greatest, and then slowly and gradually cooling the device to avoid reintroducing any stresses and strains. Procedures, conditions and apparatus for annealing polymeric structures are well known in the art. A wide variety of ahsorbable surgical devices can be manufactured from the polymer blends of the present invention. These include fasteners, such as staples, clips and the like and other implant devices, such as pins, bone screws, and the like devices.
As expressed hereinbefore, the surgical devices of the present invention exhibit excellent in vivo cyclic flex performance, a mechanical property which is highly desired in surgical devices particularly, fvr example, in surgical implant devices, such as surgical fastener/retainer systems which, after implantation, are subject to a variety of forces and often undergo repeated flexing.
Furthermore, surgical devices manufactured from the novel polymer blends of the present invention exhibit improved impact resistance as well as improved crazing 2 ~ 7 9 2 7 3 1 resistance. Crazing may be defined as surface cracking of the material as contrasted with impact resistance which is more a measure of a material's tendency to allow crack propagation. Crazing may be observed visually, such as for example, a polymeric article which is flexed will evidence crazing by fogging of an otherwise clear or transparent material. In surgical applications, once a surgical article crazes, ~lthough the article may continue to function for a limited period, the article may not exhibit the desired strength. Thus, a material with a more limited tendency to craze when fabricated, for example, into a surgical implant device such as a bone screw, would permit the bone screw to be torqued to a greater extent without a likelihood that the screw would craze and thereby become ineffective for its intended purpose.
The examples below are illustrative of the blends of the present invention and surgical devices derived therefrom.
1 ~--.
2~79~7~
1 E~ample l A copolymer of qlycolide and lactide is prepared as follows:
Hydroxyacetic acid (glycolic acid) is heated under nitrogen to 180C to remove impurities such as water.
Pressure is then reduced and heating is continued for two hours to yield a prepolymer of polyglycolic acid, which is recovered and powdered.
The prepolymer is heated in the presence of Sb203 at 275C under low pressure with an ar~or. pur~e and stirring. The prepolymer cracks and glycolide is distilled over and recovered in a cold vacuum receiver. Preferably, the glycolide is purified by conventional techniques, such as distillation, crystallization, and sublimation.
L-lactide is used alone or in combination with a small amount of the DL racemer. L-lactide is purified by crystallization from toluene solution. The DL racemer, if used, is purified by crystallization from ethyl acetate.
A mixture of the purified glycolide (18 mole percent) and lactide (82 mole percent) is charged to a reactor under an argon blanket. A solution of stannous octoate catalyst in diethyl ether is added to give 0.02% w.
of catalyst, based on the total weight of glycolide and lactide. The reactor is further purged with argon and held at 5 psi while heating to 170-175C. Pressure and temperature are maintained for six hours.
The reaction product is isolated, co~minuted, and treated to remove residual reactants. Any method capable of removing the unreacted monomers from the crude reaction product may be used. A preferred purification procedure is as follows.
2~7q27~
1 After comminution, the crude reaction product is contacted with ethyl ether for about 72 hours in a Soxhlet-type extractor to remove unreacted monomer. Typically, 4-10% of the starting monomers remain unreacted, and the glass transition temperature of the crude copolymer is approximately 50C. Removal of unreacted monomers raises the glass transition temperature. As ~ill be understood by one skilled in the art, the composition of the copolymer may differ slightly from the composition of the starting monomeric mixture because the lactide and glycolide are not of equal reactivity.
After the extraction period, the partially purified copolymer is slowly heated under vacuum from ambient temperature to 140-C over a period of about 48 hours. The slow rate of heating is desirable to prevent melting (strictly speaking, flowing together) of the co-polymer particles and to remove any water present.
Desirably, dry inert gas is used to purge the system, and occasionally the heating step may require more than 48 hours to reach the desired glass transition temperature. The combination of slow heating and purging with dry gas removes any residual solvent (ethyl ether) present, thereby raising the glass transition temperature.
After removal of unreacted monomers (and of solvent, if solvent extraction is used), the purified copolymer is further dried if it was not dried enough in the monomer removal step and, in any event, stored to keep it dry.
Commercially available poly(p-dioxanone) is used to prepare the polymeric blend of the invention.
Alternatively, poly(p-dioxanone) is prepared according to 2~79275 1 the procedure described in U.S. Patent No. 4,052,488 to Doddi et al.
A melt blend of the glycolide,/lactide copolymer and poly(p-dioxanone) is prepared using an extruder having a mixing head operating at a melt temperature of about 170'C
to 200C. The glycolide/lactide copolymer and polySp-dioxanone) are combined in mole ratios of 80:20 and 85:15, melt blended and the resulting polymeric blends are pelletized for subsequent use as described hereinbelow.
2~7~7~
1 Example 2 The pelletized polymeric blends of Example 1 are injection molded at a temperature of 130C to 140-C at an injection molding pressure, e.g., 1,500 to 1,750 psi, to form a series of test plates measuring 2.2 inch x. 2.7 inch x 0.070 inch. Control test plates are also injection molded from the glycolide/lactide copolymer described in Example 1, none of which are annealed. One portion of the test plates are annealed at an annealing temperature of about 85 C to lOO'C for 12 to 16 hours to remove internal stresses. A
second portion of the test plates are not annealed. Control test plates are also injection molded from the glycolide/lactide copolymer described in Example 1, none of which are annealed.
2 ~ 7 9 2 7 ~
1 Example 3 The test plates injection molded as described in Example 2 are tested for impact resistance using a standard falling dart impact tester. The test plates are designated as follows:
Control: glycolide/lactide copolymer (18/82);
unannealed Sample 1: glycolid~/lactide copolymer (18/82) blended with poly(p-dioxanone) at a weight ratio of 85:15; unannealed Sample 2: glycolide/lactide copolymer (18/82) blended with poly(p-dioxanone) at a weight ratio of 85:15; annealed Sample 3: glycolide/lactide copolymer (18/82) blended with poly(p-dioxanone3 at a weight ratio of 80:20; unannealed Sample 4: glycolide/lactide copoiymer (18/82) blended with poly(p-dioxanone) at a weight ratio of 80:20; annealed The results of the impact tests are set forth in the following Table.
TABLE
Force (in-lb) Control ¦Sample 1 ¦Sample 2 Sample 3 Sample 4 __ Mode of Failure: 1. No effect; 2. Slight fractures;
3. Indentation with some crazing;
4. Cracks at point of contact; 5. Hole punched at point of contact; 6. Shattered.
2079~75 1 These results show that the pol~eric blends of the present invention exhibit improved impact resistance as compared to a non-blended control, i.e., a glycolide/lactide copolymer without added poly(p-dioxanone). In addition, the test plates for Samples 1-4 exhibit improved resistance to crazing. Improved cyclic flex performance is also to be expected.
Claims (19)
1. A polymer composition, useful in the production of absorbable surgical devices, said polymer composition comprising a blend of:
a) a polymer selected from the group consisting of glycolide homopolymer, lactide homopolymer, a mixture of glycolide homopolymer and lactide homopolymer, a glycolide/lactide copolymer and mixtures thereof; and b) from about 1 to about 20 weight percent of a second polymer selected from the group consisting of poly(p-dioxanone), a copolymer of p-dioxanone and glycolide, a copolymer of p-dioxanone and lactide, a copolymer of p-dioxanone, glycolide and lactide and a copolymer of p-dioxanone and glycolide/lactide copolymer, based on the total weight of the blend.
a) a polymer selected from the group consisting of glycolide homopolymer, lactide homopolymer, a mixture of glycolide homopolymer and lactide homopolymer, a glycolide/lactide copolymer and mixtures thereof; and b) from about 1 to about 20 weight percent of a second polymer selected from the group consisting of poly(p-dioxanone), a copolymer of p-dioxanone and glycolide, a copolymer of p-dioxanone and lactide, a copolymer of p-dioxanone, glycolide and lactide and a copolymer of p-dioxanone and glycolide/lactide copolymer, based on the total weight of the blend.
2. The polymer composition of Claim 1 wherein component (a) is a copolymer of glycolide and lactide.
3. The polymer composition of Claim 2 wherein said copolymer comprises up to about 50 mole percent glycolide.
4. The polymer composition of Claim 1 wherein component b) is poly(p-dioxanone) and is present in an amount of from about 5 to about 20 weight percent, based on the total weight of the blend.
5. The polymer composition of Claim 2 wherein the glycolide/lactide copolymer has an inherent viscosity of from about 0.9 to about 2.0 dl/g measured at 30°C at a concentration of 0.25 g/dl in chloroform or hexafluoroisopropanol.
6. The polymer composition of Claim 4 wherein said poly(p-dioxanone) has an inherent viscosity of from about 0.4 to about 1.8 measured at 30°C at a concentration of 0.25 g/dl in chloroform or hexafluoroisopropanol.
7. The polymer composition of Claim 2 wherein the glycolide/lactide copolymer comprises a multi-phase composition, the first phase having from about 0 to about 25 mole percent glycolide moieties and about 75 to about 100 mole percent lactide moieties and the other phase or phases having glycolide and lactide moieties in amounts such that the composition overall has up to 45 mole percent glycolide moieties, wherein the first phase constitutes at least 50%
by weight of the copolymer.
by weight of the copolymer.
8. The polymer of Claim 1 wherein component b) is a copolymer of p-dioxanone wherein p-dioxanone comprises about 80 mole percent of said copolymer.
9. An absorbable surgical device derived from a polymer composition comprising a blend of:
(a) a polymer selected from the group consisting of glycolide homopolymer, lactide homopolymer, a mixture of glycolide homopolymer and lactide homopolymer, a glycolide/lactide copolymer and mixtures thereof; and b) from about 1 to about 20 weight percent of a second polymer selected from the group consisting of poly(p-dioxanone), a copolymer of p-dioxanone and glycolide, a copolymer of p-dioxanone and lactide, a copolymer of p-dioxanone, glycolide and lactide and a copolymer of p-dioxanone and glycolide/lactide copolymer based on the total weight of the blend.
(a) a polymer selected from the group consisting of glycolide homopolymer, lactide homopolymer, a mixture of glycolide homopolymer and lactide homopolymer, a glycolide/lactide copolymer and mixtures thereof; and b) from about 1 to about 20 weight percent of a second polymer selected from the group consisting of poly(p-dioxanone), a copolymer of p-dioxanone and glycolide, a copolymer of p-dioxanone and lactide, a copolymer of p-dioxanone, glycolide and lactide and a copolymer of p-dioxanone and glycolide/lactide copolymer based on the total weight of the blend.
10. The absorbable surgical device of Claim 9 wherein component (a) is a copolymer of glycolide and lactide.
11. The absorbable surgical device of Claim 10 wherein said copolymer comprises up to about 50 mole percent glycolide.
12. The absorbable surgical device of Claim 9 wherein component b) is poly(p-dioxanone) and is present in said blend in an amount of from about 5 to about 20 weight percent, based on the total weight of the blend.
13. The absorbable surgical device of Claim 10 wherein said glycolide/lactide copolymer has an inherent viscosity of from about 0.9 to about 2.0 dl/g measured at 30°C.
14. The absorbable surgical device of Claim 12 wherein said poly(p-dioxanone) has an inherent viscosity of from about 0.4 to about 1.8 dl/g measured at 30°C at a concentration of 0.25 g/dl in chloroform or hexafluoroisopropanol.
15. The absorbable surgical device of Claim 9 wherein component b) is a copolymer of p-dioxanone wherein p-dioxanone comprises about 80 mole percent of said copolymer.
16. The absorbable surgical device of claim 9 wherein component b) is a copolymer of p-dioxanone wherein p-dioxanone comprises about 90 mole percent of said copolymer.
17. The absorbable surgical device of Claim 9 selected from the group consisting of a fastener, retainer, pin and bone screw.
18. Use of the polymer composition of any one of claims 1, 2, 3, 4, 5, 6, 7, or 8 for an absorbable surgical device.
19. In a method of manufacturing a surgical device, the improvement comprising forming said device of a composition of any one of claims 1, 2, 3, 4, 5, 6, 7 or 8.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US76817791A | 1991-09-30 | 1991-09-30 | |
| US07/768,177 | 1991-09-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2079275A1 true CA2079275A1 (en) | 1993-03-31 |
Family
ID=25081771
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002079275A Abandoned CA2079275A1 (en) | 1991-09-30 | 1992-09-28 | Blends of glycolide and/or lactide polymers and poly(p-dioxanone) homopolymers and copolymers and absorbable surgical devices made therefrom |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2079275A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0707044A2 (en) | 1994-10-11 | 1996-04-17 | Ethicon, Inc. | Absorbable polymer blends |
| CN117982740A (en) * | 2024-04-07 | 2024-05-07 | 四川国纳科技有限公司 | Absorbable biomedical polymer material, ligature clip and preparation method |
-
1992
- 1992-09-28 CA CA002079275A patent/CA2079275A1/en not_active Abandoned
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0707044A2 (en) | 1994-10-11 | 1996-04-17 | Ethicon, Inc. | Absorbable polymer blends |
| US5641501A (en) * | 1994-10-11 | 1997-06-24 | Ethicon, Inc. | Absorbable polymer blends |
| CN117982740A (en) * | 2024-04-07 | 2024-05-07 | 四川国纳科技有限公司 | Absorbable biomedical polymer material, ligature clip and preparation method |
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