CA2035153A1 - Crystalline copolymers of -dioxanone and -caprolactone - Google Patents
Crystalline copolymers of -dioxanone and -caprolactoneInfo
- Publication number
- CA2035153A1 CA2035153A1 CA002035153A CA2035153A CA2035153A1 CA 2035153 A1 CA2035153 A1 CA 2035153A1 CA 002035153 A CA002035153 A CA 002035153A CA 2035153 A CA2035153 A CA 2035153A CA 2035153 A1 CA2035153 A1 CA 2035153A1
- Authority
- CA
- Canada
- Prior art keywords
- copolymer
- caprolactone
- percent
- copolymers
- crystalline
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- 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
- C08G63/664—Polyesters containing oxygen in the form of ether groups derived from hydroxy carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L17/00—Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
- A61L17/06—At least partially resorbable materials
- A61L17/10—At least partially resorbable materials containing macromolecular materials
- A61L17/105—Polyesters not covered by A61L17/12
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
Abstract
ABSTRACT
Crystalline copolymers of .epsilon.-caprolactone and a monomer having the formula:
Crystalline copolymers of .epsilon.-caprolactone and a monomer having the formula:
Description
2~3~153 TITLE OF THE INVENTION
CRYSTALLINE COPOLYMERS OF p-DIOXANONE AND ~-CAPROLACTONE
BACKGROUND OF THE INVENTION
This invention relates to copolymers derived from p-diosanone and its homologs, and especially to such crystalline copolymers which can be readily melt spun to prepare fibers suitable for use as absorbable surgical sutures.
U.S. Patent 4,052,988 (Doddi) discloses the preparation of a p-diosanone homopolymer and its use as an absorbable surgical suture. This synthetic suture exhibits outstanding mechanical and biological properties which make it a viable candidate to replace natural sutures such as surgical gut and collagen for numerous applications.
One of the significant hurdles to overcome before surgeons readily accept a synthetic suture over natural sutures is the stiffness of synthetics. As an example, a well known synthetic suture, which can be prepared from a glycolide homopolymer or a copolymer of lactide and glycolide, is typically braided or twisted to prepare a multifilament suture 80 that the suture has the requisite flesibilty and handling characteristics. One of the goals of the polymer chemist attempting to synthesize polymers suitable for use as absorbable surgical sutures is to prepare a monofilament suture which has handling properties and flexibility comparable to such properties of multifilament, braided sutures commonly used in the art without sacrificing physical properties.
- 2 - 203~1~3 Although the p-diosanone homopolymer described in the Doddi patent goes a long way in reaching the goal toward the preparation of an absorbable monofilament suture with handling properties and fle~ibilty as good as a braided multifilament, it would be desirable to develop a polymer composition which has even better flesibility relative to a p-diosanone homopolymer without sacrificing physical properties.
SUMMARY OF THE INVENTION
In one aspect, the invention is a crystalline copolymer of a monomer represented by the formula:
R - C ~ 1=
R -CH HC - R
~O~
wherein each R is independently hydrogen or methyl;
and an amount of -caprolactone effective to lower the modulus of the copolymer relative to the modulus of a p-diosanone homopolymer.
In another aspect, the invention is an absorbable surgical filament prepared by melt spinning the crystalline copolymer described above.
The crystalline copolymers of this invention can be readily melt spun using conventional techniques to prepare fibers having the combination of physical and biological properties necessary for use as an absorbable monofilament surgical suture. Monofilaments prepared from the crystal~ine copolymers have a lower Young's Modulus relative to the Young's Modulus of a monofilament prepared from a p-diosanone homopolymer. A reduction in the Young's 203511~ 3 Modulus correlates to a more flesible and pliable filament, and therefore the handling characteristics of the suture are enhanced.
In preferred embodiments, especially when monofilaments are prepared from block copolymers of this invention, the straight tensile strength and knot tensile strength are substantially equivalent to these properties of a monofilament prepared from a p-diosanone homopolymer.
Lastly, the in vivo absorption profile of sutures prepared from the block copolymers of this invention is comparable to the profile of sutures prepared from a p-diosanone homopolymer. This is surprisinq since homopolymers of c-caprolactone are substantially nonabsorbable for periods up to one year.
The crystalline copolymers are useful for the preparation of absorbable surgical filaments, especially absorbable monofilament surgical sutures, although these copolymers may fin~ use in the preparation of other ~urgical devices. For e~ample, the copolymers may be used for the preparation of surgical me~hes, surgical staples, homo~tatic clips, and the like.
DETAI~ED DESCRIPTION OF THE INVENTION
The crystalline copolymers of this invention are prepared from c-caprolactone and a predominant amount of a monomer having the formula:
O ~
R - C ~ C Z O
~O~
wherein each R is independently hydrogen or methyl.
20351~
Preferably, each R iS hydrogen and the monomer is 1,4-diosan-2-one, which is commonly referred to as p-diosanone. For ease of discussion, the monomer represented by the formula above will be referred to as the p-diosanone monomer or simply, p-diosanone, but this language is intended to encompass all monomers embodied in this formula. A predominant amount of the p-diosanone monomer generally refers to an amount of monomer greater than 50 weight percent of the comonomer composition from which the crystalline copolymer of this invention is derived.
In a preferred embodiment, the crystalline copolymers have a degree of crystallinity and an intrinsic viscosity which render the copolymers suitable for estrusion into fibers or films and for injection molding into surgical devices such as staples. Advantageously, the crystallinity of the copolymers is greater than about 10 percent as measured by s-ray diffraction, so that the copolymer can maintain its structural integrity at the elevated temperatures required for extrusion and molding.
Preferably, the intrinsic viscosity of the crystalline copolymers ranges from about 0.8 to about 3.5, more preferably from about 1.2 to about 3.0 d Vg in a 0.1 g/dl solution of hesafluoroigopropyl alcohol (HFIP) at 25C. A
copolymer with an intrinsic vi wosity below about 0.8 dl/g generally lacks sufficient viscosity to provide suitable melt strength for estrusion or molding, and a copolymer with an intrinsic viscosity above about 3.5 dl~g is generally too viscous for melt processing.
The copolymers of this invention can be random or block copolymers. For the preparation of random copolymers, the amount of t-caprolactone in the monomer composition from which the random copolymer is prepared is 203~1 ~3 desirably within the range of about 2 to about 20 weight percent. Amounts below about 2 percent generally will not have the effect of reducing the modulus of the copolymer, and amounts greater than 20 percent may compromise the physical properties of the copolymer, to the extent that the copolymer may no longer be suitable for use as an absorbable surgical suture. A more preferred range is between about 2 to about lO percent, with the most preferred range being between about 2 and about 5 percent.
For the preparation of block copolymers, the concentration range for 6-caprolactone in the monomer composition from which the block copolymer is prepared is desirably between about 5 to about 40 weight percent. An amount below about 5 percent generally fails to reduce modulus and amounts greater than about 40 percent may compromise physical properties, e.g straight or knot tensile strength. A preferred range is between about 5 to about 30 weight percent, and the most preferred range is between about 5 to about 20 percent.
The random copolymers of this invention can be prepared by polymerizing the desired proportions of p-diosanone and t-caprolactone in the presence of an organometallic catalyst and an initiator at elevated temperatures. The organometallic catalyst is preferably a tin-based catalyst, e.g. stannous octoate, and is present in the monomer misture at a mole ratio of monomer to catalyst ranging from 15,000 to 40,000/1. The initiator is typically an alkanol, a glycol, a hydrosyacid, or an amine, and is present in the monomer misture at a mole ratio of monomer to initiator ranging from 750 to 2000/1.
The polymerization i8 typically carried out at a temperature range from 80 to 160C, preferably 80-140C, until the desired molecular weight and viscosity are achieved.
The preferred copolymers of this invention are block copolymers of the p-dio~anone monomer and 6-caprolactone. Unlike the random copolymers, the bloc~
copolymers are semi-crystalline and have mechanical properties substantially equiralent to the mechanical properties of a p-dio~anone homopolymer. The block copolymers can be characterized as having the following repeating blocks:
--~EO-CH2-CB2-C~2-CH2-CE~2-~ m ~0~C112~C~2~~C~2~~n polyc~prol~cton~ polydlo~on~
~ "A" bloclc) ~ "B" blocl~) wherein m and n are each a number greater than 1.
The block copolymers can be prepared as diblock copolymer8 ~-AB-) or triblock copolymers (-~AB-). Diblock copolymer~ can be prepared by first prepolymerizing e-caprolactone with a monofunctional initiator such as an alkanol or an amine, and then polymerizing p-dio~anone with the prepolymsr using standard techniques known in the art. The polymerization conditions and ratio of constituents described above for the preparation of random copolymers can be used for preparing the prepolymer and the diblock copolymer, e~cept that the prepolymerization i~ generally carried out at higher temperatures, e.q 160-190C, for a ma~imum of 24 hours. Triblock copolymers are prepared in a similar manner, e~cept that the initiator used for prepolymerization of the E-caprolactone is a difunctional initiator such as a glycol.
203~1~3 Once the desired random or block copolymer is prepared, absorbable filaments e~hibiting the requisite properties for use as surgical sutures may be prepared using conventionally accepted methodæ well known in the - 5 art by first melt e~truding the copolymer through a spinnerette to prepare fibers, drawing the fibers to create orientation, and then annealing the oriented fibers to enhance dimensional stability. Additionally, the sutures can be attached, if desired, to one or more needles. See, for esample, U.S. Patent Nos. 4,653,497 and 4,838,267, which also describe in detail the testing procedures used for determining the physical and biological properties of those monofilaments described in the esamples of this specification.
lS
In preferred embodiments of this invention, absorbable surgical monofilaments prepared from copolymers of p-diosanone and ~-caprolactone have a straight tensile strength of at least 50,000 psi, preferably 60,000 psi, and a knot tensile strength of at least 30,000 psi, preferably 40,000 psi. The Young's Modulus for preferred embodiments is typically below 400,000 psi, preferably 300,000 psi, and more preferably below 100,000. The percent elongation i8 typically less than 80 percent, preferably less than 40 percent, and more preferably less than 30 percent.
The i~ vivo absorption profile of a surgical filament implanted in the tissue of an animal is often a critical factor in determining the desirability of one synthetic suture over another. Surprisingly, the surgical filaments prepared from block copolymers of this invention in preferred embodiments eshibit an i~ vivo absorption profile comparable to that of filaments prepared from a p-dio~anone homopolymer. Complete absorption of the 203~1~3 surgical filaments of this invention implanted in tissue will generally occur not more than 210 days after implantation, while filaments prepared from a polycaprolactone homopolymer show no sign of absorption s after this period of time.
The following e~amples are intended to illustrate but in no way limit the scope of the claimed invention. AS
the terms are used in the esamples, PCL and PDO refer to polymeræ of ~-caprolactone and 1,4-diosan-2-one.
~PL~
DIBLOCK COPOLYMER OF PCL~PDO .~T 8.9/91.1 BY WT
A flame dried, 250 ml round bottom single neck flask is charged with 10 grams ~8.9 wt. percent) of monohydroxy-terminated polycaprolactone prepolymer with a weight average molecular weight of 10,000 as determined by gel permeation chromatography ~GPC) supplied by Scientific Polymer Products Inc. The reaction flask is held under high vacuum at 80C for about 64 hours. After cooling to room temperature, the reaction flask is charged with 102.1 gm ~1.0 mole, 91.1 wt. percent) of 1,4-diosan-2-one, and 0.101 ml of stannous octoate ~0.33 molar solution in toluene). The contents of the reaction flask are held under high vacuum at room temperature for about 16 hours.
The flask is fitted with a flame dried mechanical stirrer and an adapter. The reactor is purged with nitroqen three times before being vented with nitrogen. The reaction misture is heated to 90C, and maintained at this temperature for about 75 minutes. The temperature of the reaction misture is raised to 110C and maintained at this temperature for about 4 hours, lowered to 90C and maintained at this temperature for 24 hours, and then lowered to ~0C and maintained at 80C for three days.
203~1~3 g The copolymer is isolated and dried for 8 hrs at 60C, and for 8 hrs at 70C under high vacuum (0.1 mmHg) to remove any unreacted monomer (about 15 percent~. The copolymer has an inherent viscosity of 2.18 dl/g in hesafluoroisopropyl alcohol (HFIP) at 25C, and a melting point range by hot stage microscopy between 108-112C.
The copolymer is melt spun, drawn and annealed to prepare oriented, dimensionally stable filaments using conventional extrusion technigues. The mechanical and biological properties of these filaments are reported in Table 1, which also includes these properties for a p-diosanone homopolymer for comparison.
203~153 Mechanical and Biological Properties of PCL/PDO ~iblock Copolymer Example No. 1 Control Fiber ProPerties Annealed (6 hrs./80C/5% relax.) Diameter (mils) 7.96 6.6 Str. Tensile, PSI 80,023 74,000 Knot Tensile, PSI 49,759 55,000 Elongation, percent 40 29 Young's Modulus, PSI 199,836 324,000 In Vitro BSR2 ~BSR, 4 days 84 84 7 days 77 78 In Vivo Absorption3 Days after Implantation 1 PDST~ violet monofilament polydioxanone suture 2 Breaking Strength ~etention (BSR) in vitro is the percent of original straight tensile strength remaining after the indicated number of days in phosphate buffer, pH=7.27 at 50C
CRYSTALLINE COPOLYMERS OF p-DIOXANONE AND ~-CAPROLACTONE
BACKGROUND OF THE INVENTION
This invention relates to copolymers derived from p-diosanone and its homologs, and especially to such crystalline copolymers which can be readily melt spun to prepare fibers suitable for use as absorbable surgical sutures.
U.S. Patent 4,052,988 (Doddi) discloses the preparation of a p-diosanone homopolymer and its use as an absorbable surgical suture. This synthetic suture exhibits outstanding mechanical and biological properties which make it a viable candidate to replace natural sutures such as surgical gut and collagen for numerous applications.
One of the significant hurdles to overcome before surgeons readily accept a synthetic suture over natural sutures is the stiffness of synthetics. As an example, a well known synthetic suture, which can be prepared from a glycolide homopolymer or a copolymer of lactide and glycolide, is typically braided or twisted to prepare a multifilament suture 80 that the suture has the requisite flesibilty and handling characteristics. One of the goals of the polymer chemist attempting to synthesize polymers suitable for use as absorbable surgical sutures is to prepare a monofilament suture which has handling properties and flexibility comparable to such properties of multifilament, braided sutures commonly used in the art without sacrificing physical properties.
- 2 - 203~1~3 Although the p-diosanone homopolymer described in the Doddi patent goes a long way in reaching the goal toward the preparation of an absorbable monofilament suture with handling properties and fle~ibilty as good as a braided multifilament, it would be desirable to develop a polymer composition which has even better flesibility relative to a p-diosanone homopolymer without sacrificing physical properties.
SUMMARY OF THE INVENTION
In one aspect, the invention is a crystalline copolymer of a monomer represented by the formula:
R - C ~ 1=
R -CH HC - R
~O~
wherein each R is independently hydrogen or methyl;
and an amount of -caprolactone effective to lower the modulus of the copolymer relative to the modulus of a p-diosanone homopolymer.
In another aspect, the invention is an absorbable surgical filament prepared by melt spinning the crystalline copolymer described above.
The crystalline copolymers of this invention can be readily melt spun using conventional techniques to prepare fibers having the combination of physical and biological properties necessary for use as an absorbable monofilament surgical suture. Monofilaments prepared from the crystal~ine copolymers have a lower Young's Modulus relative to the Young's Modulus of a monofilament prepared from a p-diosanone homopolymer. A reduction in the Young's 203511~ 3 Modulus correlates to a more flesible and pliable filament, and therefore the handling characteristics of the suture are enhanced.
In preferred embodiments, especially when monofilaments are prepared from block copolymers of this invention, the straight tensile strength and knot tensile strength are substantially equivalent to these properties of a monofilament prepared from a p-diosanone homopolymer.
Lastly, the in vivo absorption profile of sutures prepared from the block copolymers of this invention is comparable to the profile of sutures prepared from a p-diosanone homopolymer. This is surprisinq since homopolymers of c-caprolactone are substantially nonabsorbable for periods up to one year.
The crystalline copolymers are useful for the preparation of absorbable surgical filaments, especially absorbable monofilament surgical sutures, although these copolymers may fin~ use in the preparation of other ~urgical devices. For e~ample, the copolymers may be used for the preparation of surgical me~hes, surgical staples, homo~tatic clips, and the like.
DETAI~ED DESCRIPTION OF THE INVENTION
The crystalline copolymers of this invention are prepared from c-caprolactone and a predominant amount of a monomer having the formula:
O ~
R - C ~ C Z O
~O~
wherein each R is independently hydrogen or methyl.
20351~
Preferably, each R iS hydrogen and the monomer is 1,4-diosan-2-one, which is commonly referred to as p-diosanone. For ease of discussion, the monomer represented by the formula above will be referred to as the p-diosanone monomer or simply, p-diosanone, but this language is intended to encompass all monomers embodied in this formula. A predominant amount of the p-diosanone monomer generally refers to an amount of monomer greater than 50 weight percent of the comonomer composition from which the crystalline copolymer of this invention is derived.
In a preferred embodiment, the crystalline copolymers have a degree of crystallinity and an intrinsic viscosity which render the copolymers suitable for estrusion into fibers or films and for injection molding into surgical devices such as staples. Advantageously, the crystallinity of the copolymers is greater than about 10 percent as measured by s-ray diffraction, so that the copolymer can maintain its structural integrity at the elevated temperatures required for extrusion and molding.
Preferably, the intrinsic viscosity of the crystalline copolymers ranges from about 0.8 to about 3.5, more preferably from about 1.2 to about 3.0 d Vg in a 0.1 g/dl solution of hesafluoroigopropyl alcohol (HFIP) at 25C. A
copolymer with an intrinsic vi wosity below about 0.8 dl/g generally lacks sufficient viscosity to provide suitable melt strength for estrusion or molding, and a copolymer with an intrinsic viscosity above about 3.5 dl~g is generally too viscous for melt processing.
The copolymers of this invention can be random or block copolymers. For the preparation of random copolymers, the amount of t-caprolactone in the monomer composition from which the random copolymer is prepared is 203~1 ~3 desirably within the range of about 2 to about 20 weight percent. Amounts below about 2 percent generally will not have the effect of reducing the modulus of the copolymer, and amounts greater than 20 percent may compromise the physical properties of the copolymer, to the extent that the copolymer may no longer be suitable for use as an absorbable surgical suture. A more preferred range is between about 2 to about lO percent, with the most preferred range being between about 2 and about 5 percent.
For the preparation of block copolymers, the concentration range for 6-caprolactone in the monomer composition from which the block copolymer is prepared is desirably between about 5 to about 40 weight percent. An amount below about 5 percent generally fails to reduce modulus and amounts greater than about 40 percent may compromise physical properties, e.g straight or knot tensile strength. A preferred range is between about 5 to about 30 weight percent, and the most preferred range is between about 5 to about 20 percent.
The random copolymers of this invention can be prepared by polymerizing the desired proportions of p-diosanone and t-caprolactone in the presence of an organometallic catalyst and an initiator at elevated temperatures. The organometallic catalyst is preferably a tin-based catalyst, e.g. stannous octoate, and is present in the monomer misture at a mole ratio of monomer to catalyst ranging from 15,000 to 40,000/1. The initiator is typically an alkanol, a glycol, a hydrosyacid, or an amine, and is present in the monomer misture at a mole ratio of monomer to initiator ranging from 750 to 2000/1.
The polymerization i8 typically carried out at a temperature range from 80 to 160C, preferably 80-140C, until the desired molecular weight and viscosity are achieved.
The preferred copolymers of this invention are block copolymers of the p-dio~anone monomer and 6-caprolactone. Unlike the random copolymers, the bloc~
copolymers are semi-crystalline and have mechanical properties substantially equiralent to the mechanical properties of a p-dio~anone homopolymer. The block copolymers can be characterized as having the following repeating blocks:
--~EO-CH2-CB2-C~2-CH2-CE~2-~ m ~0~C112~C~2~~C~2~~n polyc~prol~cton~ polydlo~on~
~ "A" bloclc) ~ "B" blocl~) wherein m and n are each a number greater than 1.
The block copolymers can be prepared as diblock copolymer8 ~-AB-) or triblock copolymers (-~AB-). Diblock copolymer~ can be prepared by first prepolymerizing e-caprolactone with a monofunctional initiator such as an alkanol or an amine, and then polymerizing p-dio~anone with the prepolymsr using standard techniques known in the art. The polymerization conditions and ratio of constituents described above for the preparation of random copolymers can be used for preparing the prepolymer and the diblock copolymer, e~cept that the prepolymerization i~ generally carried out at higher temperatures, e.q 160-190C, for a ma~imum of 24 hours. Triblock copolymers are prepared in a similar manner, e~cept that the initiator used for prepolymerization of the E-caprolactone is a difunctional initiator such as a glycol.
203~1~3 Once the desired random or block copolymer is prepared, absorbable filaments e~hibiting the requisite properties for use as surgical sutures may be prepared using conventionally accepted methodæ well known in the - 5 art by first melt e~truding the copolymer through a spinnerette to prepare fibers, drawing the fibers to create orientation, and then annealing the oriented fibers to enhance dimensional stability. Additionally, the sutures can be attached, if desired, to one or more needles. See, for esample, U.S. Patent Nos. 4,653,497 and 4,838,267, which also describe in detail the testing procedures used for determining the physical and biological properties of those monofilaments described in the esamples of this specification.
lS
In preferred embodiments of this invention, absorbable surgical monofilaments prepared from copolymers of p-diosanone and ~-caprolactone have a straight tensile strength of at least 50,000 psi, preferably 60,000 psi, and a knot tensile strength of at least 30,000 psi, preferably 40,000 psi. The Young's Modulus for preferred embodiments is typically below 400,000 psi, preferably 300,000 psi, and more preferably below 100,000. The percent elongation i8 typically less than 80 percent, preferably less than 40 percent, and more preferably less than 30 percent.
The i~ vivo absorption profile of a surgical filament implanted in the tissue of an animal is often a critical factor in determining the desirability of one synthetic suture over another. Surprisingly, the surgical filaments prepared from block copolymers of this invention in preferred embodiments eshibit an i~ vivo absorption profile comparable to that of filaments prepared from a p-dio~anone homopolymer. Complete absorption of the 203~1~3 surgical filaments of this invention implanted in tissue will generally occur not more than 210 days after implantation, while filaments prepared from a polycaprolactone homopolymer show no sign of absorption s after this period of time.
The following e~amples are intended to illustrate but in no way limit the scope of the claimed invention. AS
the terms are used in the esamples, PCL and PDO refer to polymeræ of ~-caprolactone and 1,4-diosan-2-one.
~PL~
DIBLOCK COPOLYMER OF PCL~PDO .~T 8.9/91.1 BY WT
A flame dried, 250 ml round bottom single neck flask is charged with 10 grams ~8.9 wt. percent) of monohydroxy-terminated polycaprolactone prepolymer with a weight average molecular weight of 10,000 as determined by gel permeation chromatography ~GPC) supplied by Scientific Polymer Products Inc. The reaction flask is held under high vacuum at 80C for about 64 hours. After cooling to room temperature, the reaction flask is charged with 102.1 gm ~1.0 mole, 91.1 wt. percent) of 1,4-diosan-2-one, and 0.101 ml of stannous octoate ~0.33 molar solution in toluene). The contents of the reaction flask are held under high vacuum at room temperature for about 16 hours.
The flask is fitted with a flame dried mechanical stirrer and an adapter. The reactor is purged with nitroqen three times before being vented with nitrogen. The reaction misture is heated to 90C, and maintained at this temperature for about 75 minutes. The temperature of the reaction misture is raised to 110C and maintained at this temperature for about 4 hours, lowered to 90C and maintained at this temperature for 24 hours, and then lowered to ~0C and maintained at 80C for three days.
203~1~3 g The copolymer is isolated and dried for 8 hrs at 60C, and for 8 hrs at 70C under high vacuum (0.1 mmHg) to remove any unreacted monomer (about 15 percent~. The copolymer has an inherent viscosity of 2.18 dl/g in hesafluoroisopropyl alcohol (HFIP) at 25C, and a melting point range by hot stage microscopy between 108-112C.
The copolymer is melt spun, drawn and annealed to prepare oriented, dimensionally stable filaments using conventional extrusion technigues. The mechanical and biological properties of these filaments are reported in Table 1, which also includes these properties for a p-diosanone homopolymer for comparison.
203~153 Mechanical and Biological Properties of PCL/PDO ~iblock Copolymer Example No. 1 Control Fiber ProPerties Annealed (6 hrs./80C/5% relax.) Diameter (mils) 7.96 6.6 Str. Tensile, PSI 80,023 74,000 Knot Tensile, PSI 49,759 55,000 Elongation, percent 40 29 Young's Modulus, PSI 199,836 324,000 In Vitro BSR2 ~BSR, 4 days 84 84 7 days 77 78 In Vivo Absorption3 Days after Implantation 1 PDST~ violet monofilament polydioxanone suture 2 Breaking Strength ~etention (BSR) in vitro is the percent of original straight tensile strength remaining after the indicated number of days in phosphate buffer, pH=7.27 at 50C
3 Median percent of original cross sectional area ~emaining after intramuscular implantation in rats for the indicated number of days, determined according to the procedures described in U.S. Patent 4,653,497 2~351~3 The data from Table 1 shows that a surgical filament prepared rom a block copolymer of E-caprolactone and p-diosanone has equivalent straight and knot tensile strength relative to such properties for filaments prepared from a p-diosanone homopolymer, but has significantly enhanced flesibility as demonstrated by the reduction in Young~s Modulus relative to the filaments prepared from the p-diosanone homopolymer. Additionally, complete absorption n vivo occurred within 210 days, which is comparable to the rate of absorption for a p-diosanone homopolymer.
~3XA~.~ 2 TRIBLOCK COPOL~ER OF PCL/PDO AT 10/90 BY WT
A flame dried, 250 ml, round bottom single neck flask is charged with 54.0 g (0.4731 mole) distilled ~-caprolactone, 0.0225 ml (0.5 mmole/mole of total monomer) distilled diethylene glycol, and 0.0574 ml stannouæ octoate ~0.33 molar in toluene). The contents of the reaction 1ask are held under high vacuum at room temperature for about 4 hours. The flask is fitted with a flame dried mechanical stirrer and an adapter. The reactor is purged with nitrogen before being vented with nitrogen. The reaction misture is heated to 190C and maintained there for 16 hours. The resulting dihydrosy-terminated polycaprolactone prepolymer is isolated and dried for about 24 hours at 50C/0.1 mmHg to remove any unreacted monomer. It has an inherent visocity of 1.75 dl/g in HFIP and the free monomer is less than 0.1% by NMR.
Five grams of the dihydrosy-terminated polycaprolactone prepolymer is charged into a flame dried, 100 ml round botton, single neck flask. The contents of 203~3 the reaction flask are held under high vacuum at 50C for about 16 hours. After cooling to room temperature, the reaction flask is charged with 45 gms (0.4408 mole) of 1,4-diosan-2-one, and 0.0445 ml of stannous octoate (0.33 molar solution in toluene). The reaction flask is fitted with a flame dried mechanical stirrer and an adapter. The reactor is purged with nitrogen three times before being vented with nitrogen. The reacton mi~ture is heated to 110C and maintained there for about 8 hours. The copolymer is isolated and dried for about 64 hours at 70C/0.1 mmHg and for about 32 hours at 80C/0.lmmHg to remove any unreacted monomer. The copolymer conversion is 79%, and the copolymer has an inherent viscosity of 2.47dl/g, and a melting point of 104C.
TRIBLOCK COPO~YMER OF PCL/PDO AT 20/80 BY WT.
The procedure of Esample 2 is substantially repeated, escept that 10 gms of the polycaprolactone prepolymer are reacted with 40 gms (0.3918 mole) of 1,4-dioxan-2-one, and 0.0396 ml of stannous octoate ~0.33 molar solution in toluene). The copolymer conversion is 85%, and the copolymer has an inherent visocity of 1.82 dl/g and a melting point of 105-106C.
RANDOM COPOTYMER OF PCL~PDO AT 90/10 B~ WT.
A flame dried 250 ml, round bottom single neck flask is charged with 90 gms (0.7B85 mole) of distilled t-caprolactone, 10 gms (0.0980 mole) of 1,4-dio~an-2-one, 0.0253 ml of distilled diethylene glycol, and 0.108 ml of stannous octoate (0.33 molar 203~1~3 solution in toluene). The contents of the reaction flask are held under high vacuum (0.1 mmHg) for about 16 hours.
The flask is fitted with a flame dried mechanical stirrer and an adapter. The reactor is purqed with nitrogen three times before being vented with nitrogen. The reaction misture is heated to 160C and maintained at this temperature for about 24 hours, and then cooled to 110C
and maintained at this temperature for an additional 24 hours. The copolymer is isolated and devolatilized at 50C/16 hours/0.1 mmHg and at 80C/48 hrs/0.1 mmHg. The copolymer conversion is 99.5%, and the copolymer has an inherent visocity of 3.09 dl/g and a melting point 48-50~C.
Each of the copolymers from Esamples 2-4 are melt spun, drawn and annealed to prepare oriented, dimensionally stable filaments using conventional estrusion technigues. The mechanical properties of these filaments are reported in Table 2, which also includes the mechanical properties of a homopolymer of 1,4-dioxan-2-one for comparison.
203~ ~3 l ~, O a~ o ~ a~ cJ ~D
J- O ~ . ~ ~ C~
O r~
c o ~ ~
o ~ ~o ~ In u~
,~ g O , o~ ~ 'D 0 rl ~
~, o X C~ ~-7 ~ ~ .` ~ ~ ~ ,, æ
O O
O
O ~1 ~ ~ O ~ O ~ ~ ~ 0 C
i ~ ~
~ ~ N C ~ G 1/1 0 N
Xo .~
I ~,, P.
~ ~ 0 V
.~
~o 2 ~ 0 ."
a V ~
O ~, ~ ~ V-L~ ~ ~
Z¦ '~ ~ I R _ ~ ~ O
a~ ~ a~ - l v ~ u~
~- V U ~ S~ ~ (o V V
I r~ ~ ~ ~ o ~o ~ ~ a~ ~
- 15 203~ L~ 3 The data from Table 2 shows a reduction in Young's Modulus for filaments prepared from copolymers of this invention relative to filaments prepared from a p-diosanone homopolymer, It is also noteworthy to point out that the block copolymers retain their knot tensile strength relative to a typical knot tensile strength reported for a p-dioxanone homopolymer.
10RAMDOM COPOLYMER OF PCL~PDO
A thoroughly dried mechanically stirred 5-gallon stainless steel reactor is charged under nitrogen purge 15with 13.67kg (133.90 moles) of 1,4-diosan-2-one, 804.80 gm ~7.05 mole) of E-caprolactone, 14.5 gms of D&C Violet #2 violet dye, 26.3 gms of l-dodecanol, and 22.7 ml of stannous octoate (0.33 molar in toluene). The contents of the reactor are held under vacuum for a few minutes, then the reactor is purged with nitrogen. The reaction mixture is heated to 115C and maintained there for 6 hours, and then oven cured at 80C for 115 hours. The polymer is isolated, ground, sieved, and then dried under vacuum in a tumble drier at 70C/42 hours to remove unreacted monomer. Polymer and fiber properties are summarized in Table 3.
EXAMP~E 6 30pREPARATION OF RANDOM COPO~YMER OF PCL/P~O
AT 92.5/7.5 BY MOLE
The copolymer is prepared using a procedure similar to that of E~ample 1, e~cept the following changes are made:
~03~3 1,4-dio~an-2-one 12.094 Kg (118.47 mole) -Caprolactone 1.096 Xg (9.60 mole) l-dodecanol 23.86 gm.
Sn(oct)2 20.59 ml (0.33 molar solution in toluene) Reaction Time 8 hours~l25C
144 hours/80C
Polymer and fiber properties are summarized in Table 3.
203~3 o O Ll ~10 ~ ~ ~
~o~ ~ r o Q
O o a~ . I~ In ~ ~ I` ~
E~,~ ,~ o ~D ~ C
Z ~
O .~ ~
E r~
S
~o o~ V S
~D 1~ o\O C V
,~ ~ o~ V O
U~
r~
~:1 C v o aJ ,~ ...
o ~ o o o a) ~S
v E e v ~ ~ 0 o ~ 0 I .'~ ~ v r ~ ~; 0~ ~ 0 ~ I
I 0 ~ 0 0 ~ o.
I o ~ a) L~ 0 0 0 C4 c C~ ~ o ~ ~ l s 0 ~ e ,~ ~
o 0 ~ ~ ~ ~ , ~
I .~1 C~ ~ r~ a) v ~ ~ o P~ ~ a ,~ e "~, m ~0 m ~ a1 u~
eoE~J c ~ 0 ~v~ o I r~ 0 ~4 0 I ~ r~
0~ ~ ~ r~ Q) Q)~ 0 0 0 :~ C
~ ~ c v ~ v ~ ~ ,~
c '' ' '' a ~ e . v ~ ~ ~ ~ ~ P~
c v C~ Q ~ o o :1 ~ u~
~-,, a) I ~ .,1 v ~ ,~ o ~ ,~ ~ m c~ ~a ~ ~ ~ ~ ~ ,~ ~
- 203~1~3 The data from Table 3 shows a significant reduction in Young's Modulus for random copolymers of this invention relative to that of a p-diosanone homopolymer. Although the esamples only show the properties for copolymers of p-diosanone and ~-caprolactone in specific proportions, similar outstanding results may be obtained or copolymers derived from p-dioxanone homologs and for copolymers with varying proportions of ~-caprolactone. Such copolymers have been described in this specification and are within the scope of the claimed invention.
~3XA~.~ 2 TRIBLOCK COPOL~ER OF PCL/PDO AT 10/90 BY WT
A flame dried, 250 ml, round bottom single neck flask is charged with 54.0 g (0.4731 mole) distilled ~-caprolactone, 0.0225 ml (0.5 mmole/mole of total monomer) distilled diethylene glycol, and 0.0574 ml stannouæ octoate ~0.33 molar in toluene). The contents of the reaction 1ask are held under high vacuum at room temperature for about 4 hours. The flask is fitted with a flame dried mechanical stirrer and an adapter. The reactor is purged with nitrogen before being vented with nitrogen. The reaction misture is heated to 190C and maintained there for 16 hours. The resulting dihydrosy-terminated polycaprolactone prepolymer is isolated and dried for about 24 hours at 50C/0.1 mmHg to remove any unreacted monomer. It has an inherent visocity of 1.75 dl/g in HFIP and the free monomer is less than 0.1% by NMR.
Five grams of the dihydrosy-terminated polycaprolactone prepolymer is charged into a flame dried, 100 ml round botton, single neck flask. The contents of 203~3 the reaction flask are held under high vacuum at 50C for about 16 hours. After cooling to room temperature, the reaction flask is charged with 45 gms (0.4408 mole) of 1,4-diosan-2-one, and 0.0445 ml of stannous octoate (0.33 molar solution in toluene). The reaction flask is fitted with a flame dried mechanical stirrer and an adapter. The reactor is purged with nitrogen three times before being vented with nitrogen. The reacton mi~ture is heated to 110C and maintained there for about 8 hours. The copolymer is isolated and dried for about 64 hours at 70C/0.1 mmHg and for about 32 hours at 80C/0.lmmHg to remove any unreacted monomer. The copolymer conversion is 79%, and the copolymer has an inherent viscosity of 2.47dl/g, and a melting point of 104C.
TRIBLOCK COPO~YMER OF PCL/PDO AT 20/80 BY WT.
The procedure of Esample 2 is substantially repeated, escept that 10 gms of the polycaprolactone prepolymer are reacted with 40 gms (0.3918 mole) of 1,4-dioxan-2-one, and 0.0396 ml of stannous octoate ~0.33 molar solution in toluene). The copolymer conversion is 85%, and the copolymer has an inherent visocity of 1.82 dl/g and a melting point of 105-106C.
RANDOM COPOTYMER OF PCL~PDO AT 90/10 B~ WT.
A flame dried 250 ml, round bottom single neck flask is charged with 90 gms (0.7B85 mole) of distilled t-caprolactone, 10 gms (0.0980 mole) of 1,4-dio~an-2-one, 0.0253 ml of distilled diethylene glycol, and 0.108 ml of stannous octoate (0.33 molar 203~1~3 solution in toluene). The contents of the reaction flask are held under high vacuum (0.1 mmHg) for about 16 hours.
The flask is fitted with a flame dried mechanical stirrer and an adapter. The reactor is purqed with nitrogen three times before being vented with nitrogen. The reaction misture is heated to 160C and maintained at this temperature for about 24 hours, and then cooled to 110C
and maintained at this temperature for an additional 24 hours. The copolymer is isolated and devolatilized at 50C/16 hours/0.1 mmHg and at 80C/48 hrs/0.1 mmHg. The copolymer conversion is 99.5%, and the copolymer has an inherent visocity of 3.09 dl/g and a melting point 48-50~C.
Each of the copolymers from Esamples 2-4 are melt spun, drawn and annealed to prepare oriented, dimensionally stable filaments using conventional estrusion technigues. The mechanical properties of these filaments are reported in Table 2, which also includes the mechanical properties of a homopolymer of 1,4-dioxan-2-one for comparison.
203~ ~3 l ~, O a~ o ~ a~ cJ ~D
J- O ~ . ~ ~ C~
O r~
c o ~ ~
o ~ ~o ~ In u~
,~ g O , o~ ~ 'D 0 rl ~
~, o X C~ ~-7 ~ ~ .` ~ ~ ~ ,, æ
O O
O
O ~1 ~ ~ O ~ O ~ ~ ~ 0 C
i ~ ~
~ ~ N C ~ G 1/1 0 N
Xo .~
I ~,, P.
~ ~ 0 V
.~
~o 2 ~ 0 ."
a V ~
O ~, ~ ~ V-L~ ~ ~
Z¦ '~ ~ I R _ ~ ~ O
a~ ~ a~ - l v ~ u~
~- V U ~ S~ ~ (o V V
I r~ ~ ~ ~ o ~o ~ ~ a~ ~
- 15 203~ L~ 3 The data from Table 2 shows a reduction in Young's Modulus for filaments prepared from copolymers of this invention relative to filaments prepared from a p-diosanone homopolymer, It is also noteworthy to point out that the block copolymers retain their knot tensile strength relative to a typical knot tensile strength reported for a p-dioxanone homopolymer.
10RAMDOM COPOLYMER OF PCL~PDO
A thoroughly dried mechanically stirred 5-gallon stainless steel reactor is charged under nitrogen purge 15with 13.67kg (133.90 moles) of 1,4-diosan-2-one, 804.80 gm ~7.05 mole) of E-caprolactone, 14.5 gms of D&C Violet #2 violet dye, 26.3 gms of l-dodecanol, and 22.7 ml of stannous octoate (0.33 molar in toluene). The contents of the reactor are held under vacuum for a few minutes, then the reactor is purged with nitrogen. The reaction mixture is heated to 115C and maintained there for 6 hours, and then oven cured at 80C for 115 hours. The polymer is isolated, ground, sieved, and then dried under vacuum in a tumble drier at 70C/42 hours to remove unreacted monomer. Polymer and fiber properties are summarized in Table 3.
EXAMP~E 6 30pREPARATION OF RANDOM COPO~YMER OF PCL/P~O
AT 92.5/7.5 BY MOLE
The copolymer is prepared using a procedure similar to that of E~ample 1, e~cept the following changes are made:
~03~3 1,4-dio~an-2-one 12.094 Kg (118.47 mole) -Caprolactone 1.096 Xg (9.60 mole) l-dodecanol 23.86 gm.
Sn(oct)2 20.59 ml (0.33 molar solution in toluene) Reaction Time 8 hours~l25C
144 hours/80C
Polymer and fiber properties are summarized in Table 3.
203~3 o O Ll ~10 ~ ~ ~
~o~ ~ r o Q
O o a~ . I~ In ~ ~ I` ~
E~,~ ,~ o ~D ~ C
Z ~
O .~ ~
E r~
S
~o o~ V S
~D 1~ o\O C V
,~ ~ o~ V O
U~
r~
~:1 C v o aJ ,~ ...
o ~ o o o a) ~S
v E e v ~ ~ 0 o ~ 0 I .'~ ~ v r ~ ~; 0~ ~ 0 ~ I
I 0 ~ 0 0 ~ o.
I o ~ a) L~ 0 0 0 C4 c C~ ~ o ~ ~ l s 0 ~ e ,~ ~
o 0 ~ ~ ~ ~ , ~
I .~1 C~ ~ r~ a) v ~ ~ o P~ ~ a ,~ e "~, m ~0 m ~ a1 u~
eoE~J c ~ 0 ~v~ o I r~ 0 ~4 0 I ~ r~
0~ ~ ~ r~ Q) Q)~ 0 0 0 :~ C
~ ~ c v ~ v ~ ~ ,~
c '' ' '' a ~ e . v ~ ~ ~ ~ ~ P~
c v C~ Q ~ o o :1 ~ u~
~-,, a) I ~ .,1 v ~ ,~ o ~ ,~ ~ m c~ ~a ~ ~ ~ ~ ~ ,~ ~
- 203~1~3 The data from Table 3 shows a significant reduction in Young's Modulus for random copolymers of this invention relative to that of a p-diosanone homopolymer. Although the esamples only show the properties for copolymers of p-diosanone and ~-caprolactone in specific proportions, similar outstanding results may be obtained or copolymers derived from p-dioxanone homologs and for copolymers with varying proportions of ~-caprolactone. Such copolymers have been described in this specification and are within the scope of the claimed invention.
Claims (15)
1. A crystalline copolymer of a monomer represented by the formula and an amount of .epsilon.-caprolactone effective to lower the modulus of the copolymer relative to the modulus of a p-dioxanone homopolymer.
2. The crystalline copolymer of claim 1 wherein the crystallinity of the copolymer is greater than about 10 percent as measured by x-ray diffraction.
3. The crystalline copolymer of claim 2 wherein the intrinsic viscosity of the copolymer ranges from about 1.2 to about 3.0 dl/g.
4. The crystalline copolymer of claim 3 wherein the copolymer is a block copolymer.
5. The crystalline copolymer of claim 4 wherein the monomer represented by the formula is 1,4-dioxan-2-one.
6. The crystalline copolymer of claim 5 wherein the amount of .epsilon.-caprolactone ranges from about 5 to about 40 weight percent.
7. The crystalline copolymer of claim 6 wherein the amount of .epsilon.-caprolactone ranges from about 5 to about 30 weight percent.
8. The crystalline copolymer of claim 7 wherein the amount of .epsilon.-caprolactone ranges from about 10 to about 20 weight percent.
9. An absorbable surgical filament prepared by melt spinning the copolymer of claim 1 or 8.
10. The absorbable surgical filament of claim 9 wherein the Young's Modulus is not greater than 300,000 psi.
11. The absorbable surgical filament of claim 10 wherein complete in vivo absorption of the filament implanted in an animal is not more than 210 days after implantation.
12. The absorbable surgical filament of claim 11 wherein the straight tensile strength is at least 50,000 psi and the knot tensile strength is at least 30,000 psi.
13. The absorbable surgical filament of claim 12 wherein the percent elongation is not greater than 80 percent.
14. The absorbable surgical filament of claim 13 in the form of a monofilament.
15. The absorbable surgical filament of claim 14 in the form of a suture with or without a needle.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/472,134 US5047048A (en) | 1990-01-30 | 1990-01-30 | Crystalline copolymers of p-dioxanone and ε-caprolactone |
| US472,134 | 1990-01-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2035153A1 true CA2035153A1 (en) | 1991-07-31 |
Family
ID=23874327
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002035153A Abandoned CA2035153A1 (en) | 1990-01-30 | 1991-01-29 | Crystalline copolymers of -dioxanone and -caprolactone |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US5047048A (en) |
| EP (1) | EP0440416B1 (en) |
| JP (1) | JP3130060B2 (en) |
| AU (1) | AU631043B2 (en) |
| BR (1) | BR9100369A (en) |
| CA (1) | CA2035153A1 (en) |
| DE (1) | DE69131029T2 (en) |
Families Citing this family (54)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5120802A (en) * | 1987-12-17 | 1992-06-09 | Allied-Signal Inc. | Polycarbonate-based block copolymers and devices |
| US5451461A (en) * | 1989-09-01 | 1995-09-19 | Ethicon, Inc. | Thermal treatment of thermoplastic filaments for the preparation of surgical sutures |
| US6228954B1 (en) | 1991-02-12 | 2001-05-08 | United States Surgical Corporation | Blends of glycolide and/or lactide polymers and caprolactone and/or trimethylene carbonate polymers and absorabable surgical devices made therefrom |
| US5320624A (en) * | 1991-02-12 | 1994-06-14 | United States Surgical Corporation | Blends of glycolide and/or lactide polymers and caprolactone and/or trimethylene carbonate polymers and absorbable surgical devices made therefrom |
| US5502159A (en) * | 1991-04-17 | 1996-03-26 | United States Surgical Corporation | Absorbable composition |
| US5225520A (en) * | 1991-04-17 | 1993-07-06 | United States Surgical Corporation | Absorbable composition |
| US5468253A (en) * | 1993-01-21 | 1995-11-21 | Ethicon, Inc. | Elastomeric medical device |
| US5371176A (en) * | 1993-02-05 | 1994-12-06 | Ethicon, Inc. | Castor oil polymers |
| US5391768A (en) * | 1993-03-25 | 1995-02-21 | United States Surgical Corporation | Purification of 1,4-dioxan-2-one by crystallization |
| US5442033A (en) * | 1993-07-20 | 1995-08-15 | Ethicon, Inc. | Liquid copolymers of epsilon-caprolactone and lactide |
| US6005019A (en) * | 1993-07-21 | 1999-12-21 | United States Surgical Corporation | Plasticizers for fibers used to form surgical devices |
| CA2127636C (en) * | 1993-07-21 | 2009-10-20 | Cheng-Kung Liu | Plasticizers for fibers used to form surgical devices |
| US5470340A (en) * | 1993-10-06 | 1995-11-28 | Ethicon, Inc. | Copolymers of (p-dioxanone/glycolide and/or lactide) and p-dioxanone |
| US5626811A (en) * | 1993-12-09 | 1997-05-06 | United States Surgical Corporation | Process of making a monofilament |
| US5391707A (en) * | 1993-12-10 | 1995-02-21 | United States Surgical Corporation | Process for the production of dioxanone |
| US5611986A (en) * | 1994-07-05 | 1997-03-18 | Ethicon, Inc. | Medical devices containing high inherent viscosity poly(p-dioxanone) |
| US20020032298A1 (en) * | 1994-07-22 | 2002-03-14 | Bennett Steven L. | Bioabsorbable branched polymers containing units derived from dioxanone and medical/surgical devices manufactured therefrom |
| US6339130B1 (en) * | 1994-07-22 | 2002-01-15 | United States Surgical Corporation | Bioabsorbable branched polymers containing units derived from dioxanone and medical/surgical devices manufactured therefrom |
| US5578662A (en) | 1994-07-22 | 1996-11-26 | United States Surgical Corporation | Bioabsorbable branched polymers containing units derived from dioxanone and medical/surgical devices manufactured therefrom |
| US6206908B1 (en) | 1994-09-16 | 2001-03-27 | United States Surgical Corporation | Absorbable polymer and surgical articles fabricated therefrom |
| US5777182A (en) * | 1994-09-30 | 1998-07-07 | Shell Oil Company | Cobalt-catalyzed process for preparing 1,3-propanidiol |
| US5641501A (en) | 1994-10-11 | 1997-06-24 | Ethicon, Inc. | Absorbable polymer blends |
| AU3795395A (en) | 1994-11-30 | 1996-06-06 | Ethicon Inc. | Hard tissue bone cements and substitutes |
| CN1149596A (en) * | 1995-08-23 | 1997-05-14 | 联合碳化化学品及塑料技术公司 | Stable dioxaneone polymer |
| US5717059A (en) * | 1995-12-14 | 1998-02-10 | Shell Oil Company | Method for preparing poly-p-dioxanone polymer |
| US5997568A (en) * | 1996-01-19 | 1999-12-07 | United States Surgical Corporation | Absorbable polymer blends and surgical articles fabricated therefrom |
| US5716376A (en) | 1996-06-28 | 1998-02-10 | United States Surgical Corporation | Absorbable mixture and coatings for surgical articles fabricated therefrom |
| DE19641335A1 (en) * | 1996-10-08 | 1998-04-09 | Inst Textil & Faserforschung | Triblock terpolymer, its use in surgical sutures and manufacturing methods |
| DE19641334A1 (en) * | 1996-10-08 | 1998-04-09 | Inst Textil & Faserforschung | Triblock terpolymer, its use in medical products and manufacturing processes |
| US6201071B1 (en) * | 1997-06-25 | 2001-03-13 | Daiso Co., Ltd. | Polyether copolymer, solid polymer electrolyte and battery |
| US6494898B1 (en) | 1998-02-25 | 2002-12-17 | United States Surgical Corporation | Absorbable copolymers and surgical articles fabricated therefrom |
| US6165202A (en) * | 1998-07-06 | 2000-12-26 | United States Surgical Corporation | Absorbable polymers and surgical articles fabricated therefrom |
| US6235869B1 (en) | 1998-10-20 | 2001-05-22 | United States Surgical Corporation | Absorbable polymers and surgical articles fabricated therefrom |
| EP1309279A4 (en) * | 2000-08-17 | 2008-04-09 | Tyco Healthcare | Sutures and coatings made from therapeutic absorbable glass |
| US20030236319A1 (en) * | 2002-06-25 | 2003-12-25 | Hye-Sung Yoon | Block copolymers for surgical articles |
| ES2327918T3 (en) * | 2002-10-28 | 2009-11-05 | Tyco Healthcare Group Lp | BIOABSORBIBLE ADHESIVE COMPOUNDS. |
| US7138464B2 (en) | 2002-10-31 | 2006-11-21 | Poly Med, Inc | Functionalized, absorbable, segmented copolyesters and related copolymers |
| EP2407125A1 (en) | 2003-01-24 | 2012-01-18 | Tyco Healthcare Group, LP | Bioabsorbable composition and coatings including same |
| US20050202067A1 (en) * | 2003-10-28 | 2005-09-15 | Gkss Forschungszentrum | Matrix structure and hybrid matrix system for inducing a neofacia, their use and method for generating a neofacia |
| EP1737391A2 (en) * | 2004-04-13 | 2007-01-03 | Cook Incorporated | Implantable frame with variable compliance |
| US8263105B2 (en) | 2004-12-01 | 2012-09-11 | Tyco Healthcare Group Lp | Biomaterial drug delivery and surface modification compositions |
| US20060276882A1 (en) * | 2005-04-11 | 2006-12-07 | Cook Incorporated | Medical device including remodelable material attached to frame |
| US8500947B2 (en) | 2007-11-15 | 2013-08-06 | Covidien Lp | Speeding cure rate of bioadhesives |
| US8269025B2 (en) | 2008-07-03 | 2012-09-18 | Tyco Healthcare Group Lp | Purification of p-dioxanone |
| US20100094338A1 (en) * | 2008-10-15 | 2010-04-15 | Tyco Healthcare Group Lp | Hydroxamate-initiated polymers |
| US7923439B2 (en) * | 2008-10-15 | 2011-04-12 | Tyco Healthcare Group Lp | Hydroxamate compositions |
| US20100094340A1 (en) | 2008-10-15 | 2010-04-15 | Tyco Healthcare Group Lp | Coating compositions |
| KR100942822B1 (en) * | 2008-12-31 | 2010-02-18 | 주식회사 삼양사 | Scaffolds for tissue regeneration comprising poly-paradioxanone-caprolactone copolymer |
| US20130005829A1 (en) | 2011-06-30 | 2013-01-03 | Advanced Technologies And Regenerative Medicine, Llc. | Segmented, epsilon-Caprolactone-Rich, Poly(epsilon-Caprolactone-co-p-Dioxanone) Copolymers for Medical Applications and Devices Therefrom |
| EP2811939B8 (en) | 2012-02-10 | 2017-11-15 | CVDevices, LLC | Products made of biological tissues for stents and methods of manufacturing |
| US20130236499A1 (en) | 2012-03-12 | 2013-09-12 | Sasa Andjelic | Segmented, Semicrystalline Poly(Lactide-co-epsilon-Caprolactone) Absorbable Copolymers |
| US20140228937A1 (en) | 2013-02-11 | 2014-08-14 | Joshua Krieger | Expandable Support Frame and Medical Device |
| US10300165B2 (en) | 2016-01-20 | 2019-05-28 | Ethicon, Inc. | Segmented, p-Dioxanone-Rich, Poly(p-Dioxanone-co-epsilon-Caprolactone) copolymers for medical applications and devices made therefrom |
| KR101888642B1 (en) * | 2017-12-01 | 2018-08-16 | 주식회사 큐어바이오텍 | Method for preparing biodegradable resin and biodegradable resin prepared the same |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3523921A (en) * | 1968-06-05 | 1970-08-11 | Gaf Corp | Polylactone rubbers and methods for making same |
| US4027676A (en) * | 1975-01-07 | 1977-06-07 | Ethicon, Inc. | Coated sutures |
| US4052988A (en) * | 1976-01-12 | 1977-10-11 | Ethicon, Inc. | Synthetic absorbable surgical devices of poly-dioxanone |
| US4605730A (en) * | 1982-10-01 | 1986-08-12 | Ethicon, Inc. | Surgical articles of copolymers of glycolide and ε-caprolactone and methods of producing the same |
| US4700704A (en) * | 1982-10-01 | 1987-10-20 | Ethicon, Inc. | Surgical articles of copolymers of glycolide and ε-caprolactone and methods of producing the same |
| US4624256A (en) * | 1985-09-11 | 1986-11-25 | Pfizer Hospital Products Group, Inc. | Caprolactone polymers for suture coating |
| US4643191A (en) * | 1985-11-29 | 1987-02-17 | Ethicon, Inc. | Crystalline copolymers of p-dioxanone and lactide and surgical devices made therefrom |
| US4788979A (en) * | 1986-09-23 | 1988-12-06 | American Cyanamid Company | Bioabsorbable coating for a surgical article |
| ES2040719T3 (en) * | 1986-09-23 | 1993-11-01 | American Cyanamid Company | BIO-ABSORBABLE COATING FOR A SURGICAL ARTICLE. |
| CA1337498C (en) * | 1989-09-01 | 1995-11-07 | Ephraim Broyer | Thermal treatment of thermoplastic filaments |
-
1990
- 1990-01-30 US US07/472,134 patent/US5047048A/en not_active Expired - Lifetime
-
1991
- 1991-01-24 AU AU69973/91A patent/AU631043B2/en not_active Expired
- 1991-01-29 BR BR919100369A patent/BR9100369A/en not_active Application Discontinuation
- 1991-01-29 JP JP03026641A patent/JP3130060B2/en not_active Expired - Lifetime
- 1991-01-29 CA CA002035153A patent/CA2035153A1/en not_active Abandoned
- 1991-01-29 DE DE69131029T patent/DE69131029T2/en not_active Expired - Lifetime
- 1991-01-29 EP EP91300657A patent/EP0440416B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| DE69131029T2 (en) | 1999-11-11 |
| AU6997391A (en) | 1991-08-01 |
| EP0440416A2 (en) | 1991-08-07 |
| BR9100369A (en) | 1991-10-22 |
| JP3130060B2 (en) | 2001-01-31 |
| US5047048A (en) | 1991-09-10 |
| EP0440416A3 (en) | 1993-03-10 |
| EP0440416B1 (en) | 1999-03-24 |
| JPH04212365A (en) | 1992-08-03 |
| AU631043B2 (en) | 1992-11-12 |
| DE69131029D1 (en) | 1999-04-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5047048A (en) | Crystalline copolymers of p-dioxanone and ε-caprolactone | |
| US5007923A (en) | Crystalline copolyesters of amorphous (lactide/glycolide) and p-dioxanone | |
| US5133739A (en) | Segmented copolymers of ε-caprolactone and glycolide | |
| CA1281483C (en) | Crystalline copolymers of p-dioxanone and lactide and surgical devices made therefrom | |
| US4653497A (en) | Crystalline p-dioxanone/glycolide copolymers and surgical devices made therefrom | |
| US5376102A (en) | Deformable, absorbable surgical device | |
| US5314989A (en) | Absorbable composition | |
| US4700704A (en) | Surgical articles of copolymers of glycolide and ε-caprolactone and methods of producing the same | |
| EP0485215B1 (en) | Suture coated with a copolymer coating composition | |
| US5442032A (en) | Copolymers of 1,4-dioxepan-2-one and 1,5,8,12-tetraoxacyclotetradecane-7-14-dione | |
| US5019094A (en) | Crystalline copolymers of p-dioxanone and poly(alkylene oxides) | |
| EP1260533B1 (en) | High strengh fibers of i-lactide copolymers, e-caprolactone, and trimethylene carbonate and absorbable medical constructs thereof | |
| US5502159A (en) | Absorbable composition | |
| EP0647669B1 (en) | Copolymers of (p-dioxanone/glycolide and/or lactide) and p-dioxanone | |
| AU631291B2 (en) | Segmented copolymers of epsilon-caprolactone and glycolide | |
| KR100529705B1 (en) | A block copolymer for surgical articles | |
| US8298260B2 (en) | Compliant, long-lasting absorbable monofilament sutures |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |