NZ205680A - Glycolide/epsilon-caprolactone copolymers and sterile surgical articles made therefrom - Google Patents
Glycolide/epsilon-caprolactone copolymers and sterile surgical articles made therefromInfo
- Publication number
- NZ205680A NZ205680A NZ20568083A NZ20568083A NZ205680A NZ 205680 A NZ205680 A NZ 205680A NZ 20568083 A NZ20568083 A NZ 20568083A NZ 20568083 A NZ20568083 A NZ 20568083A NZ 205680 A NZ205680 A NZ 205680A
- Authority
- NZ
- New Zealand
- Prior art keywords
- glycolide
- percent
- caprolactone
- copolymer
- sterile
- Prior art date
Links
- 229920001577 copolymer Polymers 0.000 title claims description 93
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 title claims description 47
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 31
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 239000000178 monomer Substances 0.000 claims description 22
- 238000006116 polymerization reaction Methods 0.000 claims description 19
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 18
- 239000000463 material Substances 0.000 claims description 18
- 229920000642 polymer Polymers 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 14
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 claims description 14
- 229920001730 Moisture cure polyurethane Polymers 0.000 claims description 11
- 239000003054 catalyst Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 229910044991 metal oxide Inorganic materials 0.000 claims description 3
- 150000004706 metal oxides Chemical class 0.000 claims description 3
- 230000000379 polymerizing effect Effects 0.000 claims description 3
- 101000804902 Drosophila melanogaster Xaa-Pro aminopeptidase ApepP Proteins 0.000 claims 1
- JBFHTYHTHYHCDJ-UHFFFAOYSA-N gamma-caprolactone Chemical compound CCC1CCC(=O)O1 JBFHTYHTHYHCDJ-UHFFFAOYSA-N 0.000 claims 1
- 229940074731 ophthalmologic surgical aids Drugs 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 40
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- 239000003708 ampul Substances 0.000 description 26
- 235000011187 glycerol Nutrition 0.000 description 20
- 239000000243 solution Substances 0.000 description 17
- 238000010438 heat treatment Methods 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 229920002545 silicone oil Polymers 0.000 description 11
- 239000000835 fiber Substances 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- XXMIOPMDWAUFGU-UHFFFAOYSA-N hexane-1,6-diol Chemical compound OCCCCCCO XXMIOPMDWAUFGU-UHFFFAOYSA-N 0.000 description 7
- GUTLYIVDDKVIGB-OUBTZVSYSA-N Cobalt-60 Chemical compound [60Co] GUTLYIVDDKVIGB-OUBTZVSYSA-N 0.000 description 6
- 239000004809 Teflon Substances 0.000 description 6
- 229920006362 Teflon® Polymers 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 4
- 239000003356 suture material Substances 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 238000000137 annealing Methods 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000010926 purge Methods 0.000 description 3
- 229920001897 terpolymer Polymers 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- JGFBRKRYDCGYKD-UHFFFAOYSA-N dibutyl(oxo)tin Chemical compound CCCC[Sn](=O)CCCC JGFBRKRYDCGYKD-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 238000013022 venting Methods 0.000 description 2
- JJTUDXZGHPGLLC-IMJSIDKUSA-N 4511-42-6 Chemical compound C[C@@H]1OC(=O)[C@H](C)OC1=O JJTUDXZGHPGLLC-IMJSIDKUSA-N 0.000 description 1
- 101100025412 Arabidopsis thaliana XI-A gene Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241001558496 Talpa caeca Species 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 230000009477 glass transition Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- HTUMBQDCCIXGCV-UHFFFAOYSA-N lead oxide Chemical compound [O-2].[Pb+2] HTUMBQDCCIXGCV-UHFFFAOYSA-N 0.000 description 1
- YEXPOXQUZXUXJW-UHFFFAOYSA-N lead(II) oxide Inorganic materials [Pb]=O YEXPOXQUZXUXJW-UHFFFAOYSA-N 0.000 description 1
- 238000011670 long-evans rat Methods 0.000 description 1
- 206010033675 panniculitis Diseases 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920002463 poly(p-dioxanone) polymer Polymers 0.000 description 1
- 239000000622 polydioxanone Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 238000012956 testing procedure Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
Classifications
-
- 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
- A61L17/12—Homopolymers or copolymers of glycolic acid or lactic acid
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Surgery (AREA)
- Vascular Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Polyesters Or Polycarbonates (AREA)
Description
New Zealand Paient Spedficaiion for Paient Number £05680 2056 SO HO DBflWlHBS Priority Date(s): K . J.Q, Complete Specification Filed: Class: C&SG.GS's.. £ ETH-55 6 205S80 The synthetic absorbable sutures have gained considerable acceptance in the surgical field; however, the "handle-ability" or the compliance; i.e., flexibility and "limpness", has not always been considered satisfactory in 5 monofilament configurations. It is believed that monofilament constructions are more suitable for surgical uses than the multifilament or braided configurations as they tend to produce less infection and trauma at the wound closure site. However, the monofilaments tend to be 10 stiffer and harder to handle than the braided configuration of the same diameter. Over the years, various polymer combinations have been tried in an attempt to obtain the desired very delicate interplay between the properties of suture absorbability, jm vivo strength 15 retention, initial knot strength, and high compliance or low modulus. These desired properties, other than absorbability, are obtained in some suture materials; for example, in those described in Australian Patent Application No. 53197/79 (granted as Patent No. 530057). The suture materials described have the desired strengths, compliance and flexibility but are not absorbable and, hence, are limited in their use. To the best of our knowledge the only synthetic, absorbable sutures which in some instances may have the properties as described above are those made from polydioxanone as described in U.S. Patent 4,052,988.
It should be appreciated, that to design molecular chains needed for the production of highly compliant absorbable 30 materials, an obvious route is to copolymerize suitable comonomers or mixtures of pre-polymers and monomers following procedures similar to those used in the formation of compliant non-absorbable sutures. However, such is not the case for those polymers are of the AA-BB non-35 absorbable type. Furthermore, copolymerizing comonomers of glycolide and e-caprolactone following the teaching of U.S. Patent—N©..
: N.Z. PATENT OFFICE 2 4 MAR 1936 received which describes the copolymers 2056S0 containing 15% or less of the e-caprolactone moieties does not produce compliant materials. Copolymers containing less than 15% caprolactone are random in nature and the monofilaments made therefrom display high modulus and low compliance. It is known that copolymers containing less than 85% glycolide moieties with random microstructure do not generally offer good fiber forming polymers because of their improper level of crystallinity. Hence it would be expected that copolymers containing more than 15% caprolactone sequences would have poor crystallinity and be virtually amorphous and unsuitable for the production of strong monfilament suture materials.
Summary of the Invention The present invention describes new copolymers containing specific weight percents of epsilon (&)-caprolactone and specific weight percents of glycolide or a mixture of glycolide and lactide. These new copolymers produce synthetic absorbable surgical articles having new and novel properties and produce filaments or suture materials having desirable straight and knot tensile strengths, controllable absorbability, suitable in vivo strengths while unexpectedly displaying unique high compliance characteristics and low modulus. in accordance with the present invention, the new copolymers have a tensile strength of at least 30,000 psi and a Young's modulus of less than 350,000 psi. When in filament form, sutures made from our novel copolymers preferably have a tensile strength of at least 50,000 psi and a Young's modulus of less than 250,000 psi (e.g. from about 75,000 psi to about 150,000 psi). The novel copolymers of the present invention comprise from about 20 to 35 (preferably 20 to 30) weight percent of fe-caprolactone and from 65 to 80 (preferably 70 to 80) weight percent of glyco-lide or mixtures of glycolide and lactide. In preferred embodiments of the present invention, when mixtures of glyc-lide and lactide are used, the mixture should contain less N.Z. FATEMT 0Fj: ICE 2 4 MAR !?36 received j 205680 than 20 percent by weight of L(-)lactide. The new copolymers may be used as molded or shaped articles or they may be fabricated into filaments and appropriate sutures by techniques well known in the art and may have needles attached to said suture as desired. The filaments may be annealed to produce materials having tensile strengths of at least 50,000 psi while maintaining a Young's modulus of less than 250,000 psi. Our new copolymers may be designed to retain in vivo strengths of at least 4 0 percent after 7 days while being completely absorbed in vivo in less than 15 0 days. In certain embodiments of the present invention the novel copolymers have inherent viscosities of at least 0.8 dl/g as determined on a 0.1 g/dl solution in hexafluoroisopropanol (HFIP) at 25°C. In certain embodiments of the present invention, our novel copolymers have a crystallinity of at least 5% and preferably at least 10% (e.g. at least 20%).
Also in accordance with the present invention, our novel copolymers are produced by polymerizing a mixture of glycolide and -caprolactone in the presence of from about 0.004 to 0.02 weight percent of catalyst. The catalyst may be a metal salt or oxide, preferably a tin salt or oxide as, for example, stannous octoate, dibutyltin oxide and the like. About 20 to 30 weight percent of e-caprolactone may be used in the mixture. The polymerization is carried out at a temperature of below 250°C. for a period of time sufficient to produce a conversion of the monomers to polymer of at least 80% (e.g. at least 90%). The polymerization may for example be carried out for a period of 10 hours or longer.
In other novel processes for producing the copolymers of the present invention, a first step is used to produce a low molecular weight copolymer of e-caprolactone and glycolide. In the first step, the copolymer should comprise at least 50% by weight of £"-caprolactone to obtain an E-caprolactone rich prepolymer. The first step is carried out at a temperature of below 220°C and is followed by a second step wherein additional glycolide is added to the pre-polymer. This (' f 2 056 80 / additional mixture is polymerized at a temperature of above 120°C. for a period of time sufficient to produce a conversion of at least 80%.
Polymers produced by the methods described above may be readily extruded and drawn as is well known in the art to produce oriented filamentary material. The oriented filaments may be used with or without annealing to produce r sutures. Needles may be attached to the oriented filaments to produce needled sutures. The sutures with or without needles may be sterilized by well known sterilization techniques to produce new and novel sterile surgical sutures. The polymers may also be fabricated by other techniques such as injection molding and the like and then sterilized by techniques well known in the art to produce new and novel sterile synthetic devices.
Detailed Description of the Present Invention In the following description and examples, all parts and percentages are by weight unless otherwise specified.
The method of the present invention comprises either a single stage or a two-stage polymerization process. In the single stage polymerization process, an essentially random copolymer of glycolide monomer with e-caprolactone is produced. The polymerization is carried out in a conventional manner using a polymerization reactor equipped with heating and stirring means. The polymerization is carried out in the presence of from about .004 to .02 weight percent of a metal salt or metal oxide, preferably dibutyltin oxide or stannous octoate. The polymerization is conducted with pure and dry reactants and under a dry and inert atmosphere at temperatures sufficient to maintain the reaction mixture at a temperature close to the melting point of the polymer being produced. The amount c r 205680 of e-caprolactone should be sufficient so that in the final copolymer there will be from about 20 percent by weight to 35 percent by weight of the e-caprolactone moieties. The amount of glycolide used should be sufficient so that in the final polymer there is from about 65 weight percent to about 80 weight percent of the glycolide moieties. The polymerization should be conducted for a time sufficient to have a conversion of the monomers to copolymer of at least 80 percent and preferably more than 90 percent.
The following example describes a preferred copolymer of the present invention as well as a preferred method for producing the copolymer.
Example I f A flame dried 100 ml glass ampoule equipped with a Teflon-coated magnetic spinbar is charged with 14.27 grams (0.125 mole) of e-caprolactone, 43.53 grams (0.375 moles) glycolide 0.0591 grams 1,6-hexanediol and a catalytic amount of stannous octoate (0.25 ml of a 0.033 molar solution in toluene). The pressure in the ampoule is reduced to evaporate the toluene. The ampoule is repeatedly purged and vented with dry nitrogen and the pressure adjusted with dry nitrogen to about 3/4 of an atmosphere. The ampoule is sealed with a flame. The sealed ampoule is immersed in a silicone oil bath preheated to 100°C. This temperature is maintained for 15 minutes, with stirring as long as possible, and the temperature increased to 150°C. which is maintained for 15 minutes. The temperature is raised to 190°C. and the polymerization continued for 18 hours at 190°C. The resultant copolymer is isolated, chilled, ground, and dried under vacuum at room temperature. Some unreacted monomer is removed by heating the ground copolymer under vacuum at 110°C. for 16 hours. 2056 SO Approximately 95 percent conversion of monomers to copolymer is obtained. The resultant copolymer comprises 23 percent by weight of e-caprolactone moieties and 77 percent by weight glycolide moieties. The inherent viscosity of the resultant copolymer is 1.66 dl/g as measured using a 0.1 g/dl solution in hexaflourisopropanol (HFIP) at 25° C.
Example II For comparison purposes, Example 6 described in U.S.. Patent 3,867,190 which describes a glycolide copolymer with 15 weight pecent e-caprolactone is carried out.
A flame dried 100 ml glass ampoule equipped with a Teflon-coated magnetic spinbar is charged under dry and oxygen free conditions with 6.0 grams (0.053 mole) e-caprolactone, 34.0 grams (0.293 mole) glycolide and 0.12 gram litharge. After repeated purging with nitrogen the pressure is adjusted with nitrogen to about 3/4 of an atmosphere and the ampoule is flame sealed. The sealed ampoule is immersed in a silicone oil bath and heated to 145 to 150°C. The ampoule is maintained in this temperature range for 31 hours. The copolymer is isolated, ground and dried under vacuum at room temperature. Some unreacted monomer is removed by heating the ground copolymer at reduced pressure at 110°C. for 16 hours. The conversion of monomers to copolymer is approximately 97 percent. The resultant copolymer comprises 15 percent by weight of e-caprolactone moieties and 85 percent by weight of glycolide moieties. The resultant copolymer is practically insoluble in HFIP.
Attempts to extrude and draw the copolymer to produce an oriented filament are unsuccessful as the copolymer undergoes degradation at the temperature required to obtain a uniform melt. ( 205680 Example III An attempt to make a suitable filament forming copolymer in accordance with the teachings of U.S. Patent 3,867,190 5 using the amounts and types of catalyst in accordance with the methods of the present invention is conducted.
A flame dried 100 ml glass ampoule equipped with a Teflon-coated magnetic spinbar is charged under dry and oxyg'en-10 free conditions with 6.0 grams (0.053 mole) e- caprolactone, 34.0 grams (0.293 mole) glycolide, and 0.90 ml of a 0.33 molar stannous octoate in toluene solution. The pressure in the ampoule is reduced to remove the toluene. After repeated purging and venting with 15 nitrogen the pressure is adjusted with nitrogen to about 3/4 of an atmosphere and the ampoule flame sealed. The sealed ampoule is immersed in a silicone oil bath and heated to 145 to 150°C. This temperature range is maintained for 31 hours. The copolymer is isolated, ground 20 and dried under vacuum at room temperature. Some unreac-ted monomers are removed by heating the ground copolymer at reduced pressure at 110°C. for 16 hours. Approximately 97% conversion of monomers to copolymer is obtained. The resultant copolymer comprises 15 percent by weight of e-25 caprolactone moieties and 85 percent by weight of glycolide moieties. The resultant copolymer is practically insoluble in HFIP. The resultant copolymer is not extrud-able and orientable so as to produce filament satisfactory for producing sutures. On trying to extrude the resultant 30 copolymer it undergoes degradation at the temperature range necessary to maintain a uniform melt.
In preferred embodiments of the single step method for producing the copolymers of the present invention, it is I desired that about 22 percent to 32 percent by weight of | the e-caprolactone moiety be obtained in the final jj polymer. j ETH- 556 ( r 20568 As previously described, an alternate novel method for producing the new copolymers of the present invention is to initially form a low molecular weight pre-polymer of e-caprolactone and glycolide. This pre-polymer is rich in e-caprolactone; that is, it comprises at least 50 weight percent of e-caprolactone. The pre-polymer is produced at temperatures below about 220°C. Once the pre-polymer is formed, additional glycolide or glycolide/caprolactone or lactide mixture rich in glycolide is added to the pre-polymer and the resultant mixture further polymerized at temperatures of from about 120°C. to 250°C. and preferably from about 180°C. to 240°C. This two step polymerization is carried out to a conversion of at least 85 percent.
The following is a specific example of this alternate method for producing the novel copolymers of the present invention.
Example IV A flame dried multineck glass reactor is charged under dry and oxygen free conditions with 71.8 grams (0.629 mole) e-caprolactone, 31.3 grams (0.27 mole) glycolide, 0.0882 gram glycolic acid and 0.43 ml. of a 0.33 molar stannous octoate in toluene solution. The reactor is outfitted with an adapter with a hose connection and a dry mechanical stirrer. The pressure in the reactor is reduced and the toluene removed. The reactor is purged and vented with nitrogen which is maintained at a pressure of one atmosphere for the remainder of the run. The reactor is immersed in a silicone oil bath and heated to 120°C. which is maintained for 10 minutes. Over the course of 30 minutes the temperature is increased to 200°C. which is maintained for 20 minutes. The bath is allowed to cool to 150°C, the stirrer is stopped and the reactor withdrawn from the bath. A small sample, about 0.2 grams, of the 2 056 8 reaction mass is withdrawn under a blanket of nitrogen. The sample has an inherent viscosity of 0.51 dl/g. To the reactor is added 45.6 grams (0.399 mole) e-caprolactone and 185.6 grams (1.599 moles) glycolide. The reactor is reintroduced into the silicone oil bath. The temperature drops to 120°C. which is maintained for 10 minutes while providing good stirring. In the course of 15 minutes the temperature is increased to 205°C. which is maintained for 4 hours.
The copolymer is isolated, ground, and dried under vacuum at room temperature. Some unreacted monomers are removed by heating the ground copolymer at reduced pressure at 100°C. to constant weight. A conversion of monomers to copolymer of approximately 87% is obtained. The resultant copolymer comprises 26 percent by weight of e-caprolactone moieties and 74 percent by weight of glycolide moieties. The resultant copolymer has an inherent viscosity of 1.53 dl/g as measured using a 0.1 g/dl solution in HFIP at 25°C.
Example V The procedure of Example I is essentially followed as set out in that example except that the ampoule is charged with 17.1 grams (0.150 mole) e-caprolactone, 40.6 grams (0.350 mole) glycolide, 0.1182 gram (0.001 mole), 1,6-hexanediol, and 0.25 ml. of a 0.033 molar stannous octoate in toluene solution. The sealed ampoule is immersed in a silicone oil bath preheated to 100°C. This temperature is maintained for 30 minutes with stirring as long as possible. In the course of 50 minutes the temperature is raised to 190°C which is maintained for 7 hours. The percent conversion of monomers to copolymer is approximately 90% and the resultant copolymer has an inherent 205680 -li- viscosity of 1.24 dl/g as measured using a 0.1 g/dl solution in HFIP at 25°C. The resultant copolymer comprises 23 percent by weight of e-caprolactone moieties.
Example VI The procedure of Example I is followed as set out in that example except that the ampoule is charged with 14.3 grams (0.125 moles) e-caprolactone, 43.5 grams (0.35 mole) • glycolide, 0.0591 gram (0.0005 mole) 1,6-hexanediol, and 0.51 ml. of an 0.033 molar stannous octoate in toluene. The sealed ampoule is immersed in a silicone oil bath preheated to 100°C. That temperature is maintained for 15 minutes and then increased over the course of less than an hour to 195°C. which is maintained for 2 hours. The copolymer is isolated, ground and dried under vacuum at room temperature. Some unreacted monomer is removed by heating the ground copolymer at reduced pressure at 110°C. for 16 hours. The conversion of monomers to copolymer is approximately 90%. The resultant copolymer has an inherent viscosity of 1.62 dl/g measured at 25°C. at a 0.1 g/dl concentration in HFIP. The resultant copolymer comprises 17 percent by weight of e-caprolactone moieties.
Example VII The procedure as set forth in Example IV is followed as set forth therein except the reactor is charged with 22.8 grams (0.200 mole) e-caprolactone, 10 grams (0.0862 mole) glycolide, 33.8 mg (0.286 mmole) 1,6-hexanediol, and 0.216 ml. of a 0.33 molar stannous octoate in toluene solution. The charged reactor is immersed in a silicone oil bath and heated to 190°C. over the course of 35 minutes. Heating is discontinued and the reactor in the bath allowed to cool to 120°C. over a period of 30 minutes. While maintaining the temperature at 120°C. and 56 8 0 under a nitrogen blanket 6.5 grams (0.057 mole) e-caprolactone and 59.7 grams (0.514 mole) glycolide is added to the reactor. The reaction mass is maintained at 120°C. for 40 minutes with good stirring. Over the course of 15 minutes the temperature is increased to 195°C. which is maintained for 2 1/2 hours. The copolymer is isolated, ground and dried under vacuum at room temperature. Some unreacted monomers are removed by heating the ground copolymer at reduced pressure at 85°C. for 16 hours. A-conversion of monomer to polymer of greater than 90% is obtained. The resultant copolymer has an inherent viscosity of 1.60 dl/g as measured during a 0.1 g/dl concentration in HFIP at 25°C. The resultant copolymer comprises 26 percent by weight of e-caprolactone moieties.
Example VIII The procedure as set forth in Example VII is carried out as set forth therein with the exception that the reactor is charged with 22.8 grams (0.200 mole) e-caprolactone, 7.7 grams (0.066 mole) glycolide, 0.1182 gram (0.001 mole) 1,6-hexanediol and 0.25 ml. of .033 molar stannous octoate in toluene solution. The initial polymerization is carried out at 150°C. and the reactor then further charged with 27.1 grams (0.233 mole) glycolide. The polymerization is continued for approximately 2 1/2 hours at a temperature of from 190°C. to 205°C. A percent conversion of greater than 80% is attained. The resultant copolymer has an inherent viscosity of 1.00 dl/g as measured using a 0.1 g/dl solution in HFIP at 25°C. The resultant copolymer contains 23 percent by weight of e-caprolactone moieties.
Example IX The procedure as set forth in Example VIII is followed as set forth therein except that 17.12 grams of e-5 caprolactone and 10.15 grams of glycolide are used initially, 30.47 grams of glycolide are added prior to the second polymerization and the second polymerization is carried out at 205°C. for 6 1/4 hours. A percent conversion of approximately 90% is attained. The resultant 10 copolymer has a viscosity of 1.23 dl/g as measured using a 0.1 g/dl solution in HFIP at 25°C. The resultant copolymer contains 22 percent by weight of e-caprolactone moieties.
Example X A series of experiments is run at various ratios of e-caprolactone and glycolide as shown in the following Table 1. A flame dried 100 ml glass ampoule equipped with 20 a Teflon-coated magnetic spinbar is charged with e- caprolactone and glycolide in the amounts shown in the following table and 0.1182 gram 1,6-hexanediol and a catalytic amount of stannous octoate (0.25 ml of a 0.033 molar solution in toluene). The pressure in the 25 ampoule is reduced to evaporate the toluene. After repeated purging and venting with nitrogen the pressure is adjusted with nitrogen to about 3/4 of an atmosphere and the ampoule is flame sealed. The reactor is immersed in a silicone oil bath preheated to 100°C. This temperature is 30 maintained for 15 minutes with stirring and then raised to 150°C. This temperature is maintained for 15 minutes and then raised to 190°C. which is maintained for 18 hours.
This procedure is followed with examples a through h, however, with example i, the temperature is raised to 35 205°C. which is maintained for 2 hours. The bath is ETH-556 c 20568 allowed to cool to 190°C which is maintained for the final heating period; the cooling period and final heating period total 18 hours. The polymers from each example are isolated, chilled and ground. The percent conversion and inherent viscosity as measured using a 0.1 g/dl solution in HFIP at 25°C. for each copolymer are given in the following Table 1.
Table 1 Grams (Moles) Grams (Moles) % e-caprolactone Glycolide Conversion 2.84 (0.025) 54.86 (0.47) 98 .70 (0.050) 52.53 (0.45) 98 8.56 (0.075) 49.33 (0.425) 98 11.42 (0.100) 46.43 (0.4) 97 14.27 (0.125) 43.53 (0.375) 97 17.12 (0.150) 40.62 (0.349) 97 19.98 (0.175) 37.72 (0.324) 97 17.12 (0.150) 40.62 (0.349) 95 17.12 (0.150) 40.62 (0.349) 93 P' Inherent Final Wt.
Viscosity e-caprolactone insoluble 4 insoluble 9 1.45 14 1.48 18 (fi 1.41 23 » 1.39 28 1.39 33 1.74 27 1.61 25 Ln & oo ( ( 2056 80 Example XI A flame dried 100 ml. glass ampoule equipped with a Teflon-coated magnetic spinbar is charged with 22.8 grams (0.200 moles) e-caprolactone, 34.8 grams (0.300 moles) glycolide, 0.1182 grams (0.001 mole) 1,6-hexanediol, and 0.25 ml of a 0.033 mole stannous octoate in toluene solution. The reactor is immersed in a silicone oil bath preheated to 100°C. This temperature is maintained for 15.. minutes with stirring. The temperature is increased to 150°C. and maintained for 30 minutes and then increased to 190°C. which is maintained for 17 hours. The polymer is isolated, ground and dried under vacuum at room temperature. Some unreacted monomer is remove by heating the ground polymer at reduced pressure at 110°C. for 16 hours. A conversion of monomer to polymer of better than 90% is obtained. The resultant copolymer has an inherent viscosity of 1.39 dl/g in HFIP at 25° at a concentration of 0.1 g/dl.
In this example, the resultant copolymer contains about 37% by weight of e-caprolactone moieties and the resulting copolymer is practically amorphous. It is unsuitable for manufacturing dimensionally stable oriented filaments and surgical sutures.
Example XII A flame dried 100 ml ampoule equipped with a Teflon-coated magnetic spinbar is charged with 11.41 g. of e-caprolactone (0.4 mole), 0.0739 g. 1,b-hexanediol (0.625 m.mole), and a catalytic amount of stannous octoate (0.25 ml. of an 0.033 molar solution in toluene). The pressure in the ampoule is reduced to evaporate the toluene. The ampoule is repeatedly purged and vented with dry nitrogen and the pressure adjusted with dry nitrogen C c 205680 to about 3/4 atmosphere. The ampoule is sealed with a flame. The sealed ampoule is immersed in a silicone oil bath preheated to 100°C. This temperature is maintained for 15 minutes, stirring when possible, and the tempera-5 ture increased to 150°C. and maintained for 15 minutes.
The temperature is raised to 190°C. and the polymerization continues for 18 hours at 190°C. The resultant terpolymer is isolated, chilled, ground, and dried under vacuum at room temperature. Some unreacted monomer is removed by 10 heating the ground terpolymer under vacuum at 110°C. for 16 hours; a weight loss of 2.8 percent is experienced. The inherent viscosity of the resultant terpolymer is 1.48 dl/g. in. in 0.1 g/dl solution in hexafluoroisopro-panol (HFIP) at 25°C. The new synthetic absorbable 15 copolymers of the present invention may be converted to oriented filament materials by techniques of extruding and drawing well known in the art for producing filamentous materials. The filaments may be sterilized with or without attached needles to produce sterile surgical 20 sutures as is well-known in the art. A preferred technique for extruding and drawing the copolymers of the present invention is described in the following Example.
Example XIII The copolymer is melt spun in an Instron Rheometer at a temperature at least 10°C. above the melting temperature of the copolymer. A 40 mil die with a L/D ratio of 24 is used. A sheer rate of 213 sec-1 is used for the extru-30 sion. The extrudate is taken up through ice water and wound on a spool. The wound fibers are stored at reduced pressure for 2 to 24 hours. The monofilaments are oriented by drawing in one or two stages. The drawn filaments are heat set by heating at the desired temperature ETH-556 r r 2056 80 under constant strain with or without allowing for 5% relaxation.
The filamentary materials are usually annealed as is well-known in the art under conditions which improve suture properties. The filaments may be annealed under tension at temperatures of from about 50°C. to 120°C. for periods o£ time of from 1 hour to 48 hours. In preferred embodiments we anneal our filament materials under tension at .. . temperatures of from 60°C. to 110°C. and at times from 4 to 16 hours.
The filament materials are tested for various physical properties such as knot tensile strength, straight tensile strength, elongation, and Young's modulus. The copolymers also may be tested for inherent viscosity, melting temperature and percent crystallinity.
The following describes the various test methods used to determine the properties of the filament materials and/or the copolymers.
The characteristic properties of the filaments of the present invention are readily determined by conventional test procedures. The properties are determined using an Instron tensile tester under the following conditions: crosshead speed (XH) : 2 in/min Chart.speed (S) : 10 in/min Sample length (GL) : 2 in Scale load (SL) : 21 lbs/in.
Young's modulus is calculated from the slope of the stress-strain curve of the sample in the initial linear, elastic region as follows: ( ( Young's Modulus (psi) = tanO x GL x CS x SL XH x XS t) is the angle between the slope and the horizontal, XS is the initial cross-sectional area of the fiber (in2), SL is the scale load and XH, CS, and GL are as identified above.
The straight tensile strength is calculated by dividing the force required to break (lbs) by the initial cross-sectional area of the fiber (in2). The elongation to break is read directly from the stress-strain curve of the sample allotting 10% per inch of horizontal displacement.
The knot tensile strength of a filament is determined in separate experiments. The test article is tied into a surgeon's knot with one turn of the filament around flexible tubing (1/4 inch inside diameter and 1/16 inch wall thickness). The surgeon's knot is a square knot in which the free end is first passed twice, instead of once, through the loop and pulled taut, then passed once through a second loop, and the ends drawn taut so that a single knot is superimposed upon a compound knot. The first knot is started with the left end over the right end and sufficient tension is exerted to tie the knot securely. The specimen is placed in the Instron tensile tester with the knot approximately midway between the clamps. The knot tensile strength is calculated by dividing the force required to break (lbs) by the initial cross-sectional area of the fiber (in2).
The temperature profile of a copolymer is determined using a Differential Scanning Calorimeter (DSC) by first heating the copolymer to its initial melting temperature (Tm initial) followed by rapid cooling the melted sample. The quenched coplymer is then reheated at a rate of 20° C. per • ~y' - li'/"' ( C ninute and the glass transition temperature (Tg), temperature of crystallization (Tc) and melting temperature (Tn) observed. The crystallinity of the polymer as reported is measured by X-ray diffraction techniques as 5 are well-known.
In all instances the inherent viscosity reported is measured at 25°C. at a concentration of 0.1 g/dl in hexafluorispropyl alcohol (HFIP).
The composition of the final copolymer is determine by NMR analysis.
The various copolymers produced in Examples I through XII 15 are measured for one or more of the following properties: inherent viscosity, melting temperatures and percent crystallinity. The results of these tests are given in the following Table 2: ETH- 556 I Table 2 Example e-Caprolactone In Copolymer Inherent Viscosity dl/g Tm Initial Tg Tc 23 1.66 12 75 Insoluble 225 Insoluble 221 22 115 26 1.53 166 86 23 .1.24 17 1.62 184 21 78 26 1.60 185 14 23 1.00 222 110 22 1.23 Insoluble Insoluble 1.45 225 84 1.48 221 18 98 1.41 1.39 1.39 27 1.74 223 26 90 1.61 37 1.39 —" 1.48 - - ; - T- m % Crystallinity I II III IV V VI VII VIII IX Xa Xb Xc xa Xe Xf Xg Xh Xi XI XII 165 210 203 156 178 188 213 201 200 208 33 26 31 17 35 23 33 40 34 26 21 C? i practically amorphou 0\ 00 o The copolymers of the present inention produced in accordance with the previously described Examples 1 through XII are converted to filament materials where possible as previously described. In some instances the filaments are annealed while in other instances they are not annealed. The resultant filament materials are measured for one or more of the following properties: straight tensile strength, knot tensile strength, elongation, and Young's modulus.
The results of these tests are provided in the following Table 3.
Table 3 > N lA' Example No.
I II III IV V VI VII VIII IX Xa Xb Xc Xd Xe Xf Xg Xh Xi XI XII Extrus ion Temp ° C.
Drawing Conditions Bath 240 Glycerine 240 Glycerine 220 Glycerine 180 Glycerine 185 Glycerine 215 Glycerine 225 Glycerine 180 Glycerine 185 Glycerine 235 Glycerine 230 Glycerine 235 Glycerine* 240 Glycerine 225 Glycerine 220 Glycerine 220 Glycerine 240 Glycerine 180 Glycerine Not orientable 230 [Glycerine 1st Stage 2nd Stage (Draw Ratio/°C.) /52 4/54 4/52 /51 /53 /52 4/61 /49 /51 /52 4/RT* /54 /54 /51 /53 /54 /56 /51 Annealing Conditions Relax % 1.2/74 5 Not orientable 1.375/73 1.51/71 1.2/71 1C./hr 80/6 Diam. mils. 7.8 Straight Tensile Kpsi 88 1.2/75 1.2/74 1.5/60 1.2/72 1.2/74 1.5/72 1.2/70 1.2/75 1.2/73 1.2/74 1.2/74 1.2/70 1.2/74 to dimensionally stable fiber non-uniform fiber 110/5 65/6 80/6 76/16 65/6 80/6 80/6 80/6 80/6 80/6 80/6 80/6 80/6 80/6 80/6 None '1st stage at room temperature in air; second stage in glycerine. 7.8 8.0 7.5 7.2 8.1 7.5 6.9 6.9 7.4 7.3 7.5 7.5 7.5 7.1 7.1 7.5 89 75 114 111 59 85 90 21 36 56 82 55 21 62 62 63 Knot Tens ile Kpsi 54 52 67 43 65 67 50 50 51 Elongation % 43 28 19 42 25 25 35 45 42 17 32 32 59 40 40 59 Young Modulus Kpsi 138 79 101 689 323 94 156 1131 668 386 301 100 88 38 48 48 75 to o Ctt £T\ Co ( ( 2056 Fibers made from copolymers produced in accordance with some of the Examples previously described are annealed and sterilized and tested for absorption characteristics. The percent breaking strength retention after various lengths of time is determined.
The breaking strength of a sample is determined by implanting two strands of a sample in the dorsal subcutis of each of eight (8) Long-Evans rats. Thus, 16 strands of each sample are implanted corresponding to the two implantation periods; eight examples of each sample for each of the periods. The periods of jln vivo residence are 7 and 14 days. The ratio of the mean value (of 8 determinations) of the breaking strength (determined with an Instron Tensile tester in accordance with standard testing procedure) at each period to the mean value (of 8 determinations) obtained for the sample prior to implantation constitutes its breaking strength for that period.
Table 4 provides the results of the breaking strength retention for the examples as indicated.
Table 4 Example Processing Conditions % Breaking Strength No. Annealing Sterilization Retention At 7 days 14 days IV hr./110°C.
Ethylene Oxide 44 11 VII • 16 hr./76°C.
Cobalt 60 62 37 I 6 hr./8 0°C.
Cobalt 60 54 13 Xh 6 hr./80°C.
Cobalt 60 52 12 xi 6 hr./80°C.
Cobalt 60 49 11 Xe 6 hr./80°C.
Cobalt 60 58 24 Xf 6 hr./80°C.
Cobalt 60 61 22
Claims (27)
1. A sterile surgical article of a polymeric material having a tensile strength of at least 30,000 psi and Young's modulus of less than 350,000 psi, said polymeric material comprising from 20 to 35 weight percent epsilon (£)-capro-lactone and from 65 to 80 weight percent glycolide based sequences or a mixture of glycolide and lactide based sequences in which said lactide based sequences are less than 20% by weight of said mixture.
2. A sterile surgical article according to Claim 1 comprising from 25 to 35 weight percent 6-caprolactone and 65 to 75 weight percent glycolide based sequences.
3. A sterile surgical article according to Claim 1 wherein the polymeric material has an inherent viscosity of at least 0.8 dl/g measured at 25°C. in a 0.1 g/dl solution in hexa- fluoroisopropyl alcohol.
4. A sterile surgical article according to Claim 1 wherein the article comprises an oriented filament.
5. A sterile surgical article according to Claim 4 wherein the filament is annealed.
6. A sterile surgical article according to Claim 1 wherein the article is a sterile suture having a Young's modulus of less than 250,000 psi.
7. A sterile suture according to Claim 6 having a needle attached to at least one end of said suture.
8. A sterile suture according to Claim 6 having a tensile strength of at least 50,000 psi.
9. A sterile suture according to Claim 6 or 7 comprising from 20 to 30 weight percent £-caprolactone and from 70 to 80 weight percent glycolide.
10. A sterile suture according to Claim 9 wherein the suture is a monofilament.
11. A sterile suture according to Claim 10 wherein the monofilament has been annealed.
12. A sterile suture according to Claim 6 or 7 wherein the polymeric material has an inherent viscosity of at least 0.8 dl/g measured at 25°C. in a 0.1 g/dl solution in hexafluoro-isopropyl alcohol.
13. A sterile suture according to Claim 12 wherein the polymeric material has a crystallinity of at least 20 percent.
14. A sterile surgical article according to Claim 6 or 7 wherein the polymeric material has a Young's modulus of from 75,000 psi to 150,000 psi.
15. A process for producing copolymers of glycolide and £-caprolactone, said polymers being capable of being heat formed into strong filaments having a Young's modulus of 300,000 psi or less which comprises polymerizing a mixture of glycolide and £-caprolactone in the presence of from 0.00 4 to 0.02 weight percent metal salt or metal oxide catalyst, said polymerization being carried out at a temperature below 250°C. for a period of time sufficient to produce a conversion of the monomers to copolymers of at least 80 percent wherein a copolymer having a crystallinity of at least 5 percent is produced.
16. A process according to Claim 15 wherein from 20 to 30 weight percent of ^-caprolactone is used.
17. A process according to Claim 16 wherein the catalyst is 28 205680 stannous octoate.
18. A process according to Claim 15 or 17 wherein the polymerization is carried out at a temperature of 190°C.
19. A process according to Claim 18 wherein the polymerization is carried out for 10 hours or longer.
20. A process according to Claim 19 wherein the conversion of monomers to copolymer is at least 90 percent.
21. A process according to Claim 20 wherein the copolymer has a crystallinity of at least 10 percent.
22. A process for producing a copolymer of glycolide and ^-caprolactone comprising: forming a low molecular weight pre-polymer of f'-capro-lactone and glycolide, said pre-polymer comprising more than 50 weight percent of ^-caprolactone, and being produced at a temperature below 22 0°C., and adding additional glycolide to said pre-polymer and polymerizing said mixture containing the additional glycolide at a temperature above 120°C. for a.period of time sufficient to produce a conversion to copolymer of at least 80 percent and copolymer having a crystallinity of at least 5 percent.
23. A process according to Claim 22 in which the prepolymer has at least 60 weight percent e-caprolactone.
24. A process according to Claim 22 wherein the low molecular weight pre-polymer is produced using metal salt or metal oxide as catalyst.
25. A process according to Claim 24 wherein from 0.004 to 0.02 weight percent of catalyst is used. 29 205680
26. A process according to Claim 25 wherein the catalyst is stannous octoate.
27. A process according to Claim 26 wherein a conversion to copolymer of at least 90 percent is obtained. WEST-V#tKER, McCABE psr: ATTO R N EySrOR THE AP P LI CANT. U.&. PATENT OFFICE L nrJArt ivoo RECEIVE
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US43217682A | 1982-10-01 | 1982-10-01 |
Publications (1)
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NZ205680A true NZ205680A (en) | 1986-05-09 |
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Application Number | Title | Priority Date | Filing Date |
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NZ20568083A NZ205680A (en) | 1982-10-01 | 1983-09-21 | Glycolide/epsilon-caprolactone copolymers and sterile surgical articles made therefrom |
Country Status (6)
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JP (2) | JPS5982865A (en) |
AU (1) | AU1979583A (en) |
CA (1) | CA1224600A (en) |
DE (1) | DE3335588C2 (en) |
GB (1) | GB2127839B (en) |
NZ (1) | NZ205680A (en) |
Families Citing this family (28)
Publication number | Priority date | Publication date | Assignee | Title |
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JPS63109851A (en) * | 1986-06-02 | 1988-05-14 | 三井東圧化学株式会社 | Method for preserving suturing yarn |
DE3785716T2 (en) * | 1986-09-23 | 1993-12-02 | American Cyanamid Co | Bioresorbable coating for surgical articles. |
JP2566786B2 (en) * | 1987-08-26 | 1996-12-25 | 株式会社ジェイ・エム・エス | Process for producing molded article for medical use composed of copolymer of lactic acid and ε-caprolactone |
NL8703115A (en) * | 1987-12-23 | 1989-07-17 | Groningen Science Park | BIODEGRADABLE POLYURETHANS, PREPARATIONS BASED ON THESE, AND POLYESTER POLYOL PREPOLYMERS. |
JP2520678B2 (en) * | 1987-12-30 | 1996-07-31 | 日本商事株式会社 | Surgical monofilament suture |
JP2709349B2 (en) * | 1988-08-31 | 1998-02-04 | 株式会社 ジーシー | Materials for periodontal tissue regeneration |
US5250584A (en) * | 1988-08-31 | 1993-10-05 | G-C Dental Industrial Corp. | Periodontium-regenerative materials |
US5085629A (en) * | 1988-10-06 | 1992-02-04 | Medical Engineering Corporation | Biodegradable stent |
US5252701A (en) * | 1990-07-06 | 1993-10-12 | American Cyanamid Company | Segmented absorbable copolymer |
US5272221A (en) * | 1991-04-09 | 1993-12-21 | Mitsui Toatsu Chemicals, Incorporated | Nylon composition having increased hydrolyzability and method for increasing hydrolyzability of nylon |
JP2795423B2 (en) * | 1992-07-06 | 1998-09-10 | ユルゲンス クリスチャン | Skin application |
DE69433340T2 (en) * | 1993-09-09 | 2004-08-12 | Kanebo, Ltd. | BIODEGRADABLE COPOLYESTER, MOLDED PART MADE THEREOF AND METHOD FOR PRODUCING THE MOLDED PART |
US6306166B1 (en) | 1997-08-13 | 2001-10-23 | Scimed Life Systems, Inc. | Loading and release of water-insoluble drugs |
US6186985B1 (en) | 1997-10-03 | 2001-02-13 | Boston Scientific Corporation | Gastro-intestinal tube with dissolvable support bolster |
US6369039B1 (en) | 1998-06-30 | 2002-04-09 | Scimed Life Sytems, Inc. | High efficiency local drug delivery |
US6235869B1 (en) * | 1998-10-20 | 2001-05-22 | United States Surgical Corporation | Absorbable polymers and surgical articles fabricated therefrom |
EP1048683B1 (en) * | 1998-11-13 | 2005-05-25 | DAICEL CHEMICAL INDUSTRIES, Ltd. | Aliphatic copolymer, production process, aliphatic polyester resin composition, various uses, coating composition, and agricultural or horticultural particulate composition comprising degradable coating film |
US6419866B1 (en) * | 1999-12-21 | 2002-07-16 | Ethicon, Inc. | Process of making synthetic absorbable autoclaveable monofilament fibers and brachytherapy seed spacers |
US6831149B2 (en) * | 2002-06-28 | 2004-12-14 | Ethicon, Inc. | Polymerization process using mono-and di-functional initiators to prepare fast crystallizing polylactone copolymers |
CA2673991C (en) | 2007-01-21 | 2012-02-07 | Hemoteq Ag | Methods for coating catheter balloons with a defined quantity of active agent |
US9192697B2 (en) | 2007-07-03 | 2015-11-24 | Hemoteq Ag | Balloon catheter for treating stenosis of body passages and for preventing threatening restenosis |
JP2011006496A (en) * | 2007-09-14 | 2011-01-13 | Gunze Ltd | SUTURE CONTAINING GLYCOLIDE/epsi-CAPROLACTONE COPOLYMER |
ES2550634T3 (en) | 2009-07-10 | 2015-11-11 | Boston Scientific Scimed, Inc. | Use of nanocrystals for a drug delivery balloon |
JP5933434B2 (en) | 2009-07-17 | 2016-06-08 | ボストン サイエンティフィック サイムド,インコーポレイテッドBoston Scientific Scimed,Inc. | Method for producing drug delivery balloon |
WO2012031236A1 (en) | 2010-09-02 | 2012-03-08 | Boston Scientific Scimed, Inc. | Coating process for drug delivery balloons using heat-induced rewrap memory |
WO2013022458A1 (en) | 2011-08-05 | 2013-02-14 | Boston Scientific Scimed, Inc. | Methods of converting amorphous drug substance into crystalline form |
WO2013028208A1 (en) | 2011-08-25 | 2013-02-28 | Boston Scientific Scimed, Inc. | Medical device with crystalline drug coating |
WO2019035357A1 (en) * | 2017-08-17 | 2019-02-21 | 東レ株式会社 | Polyester copolymer and method for producing same |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
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US3867190A (en) * | 1971-10-18 | 1975-02-18 | American Cyanamid Co | Reducing capillarity of polyglycolic acid sutures |
US3982543A (en) * | 1973-04-24 | 1976-09-28 | American Cyanamid Company | Reducing capillarity of polyglycolic acid sutures |
ZA782039B (en) * | 1977-05-23 | 1979-09-26 | American Cyanamid Co | Surgical articles |
US4243775A (en) * | 1978-11-13 | 1981-01-06 | American Cyanamid Company | Synthetic polyester surgical articles |
-
1983
- 1983-09-21 NZ NZ20568083A patent/NZ205680A/en unknown
- 1983-09-28 JP JP58178367A patent/JPS5982865A/en active Granted
- 1983-09-29 CA CA000437933A patent/CA1224600A/en not_active Expired
- 1983-09-30 GB GB08326335A patent/GB2127839B/en not_active Expired
- 1983-09-30 AU AU19795/83A patent/AU1979583A/en not_active Abandoned
- 1983-09-30 DE DE19833335588 patent/DE3335588C2/en not_active Expired - Lifetime
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1990
- 1990-11-30 JP JP2336838A patent/JPH0696633B2/en not_active Expired - Lifetime
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AU1979583A (en) | 1984-04-05 |
JPH0343906B2 (en) | 1991-07-04 |
GB2127839A (en) | 1984-04-18 |
JPS5982865A (en) | 1984-05-14 |
DE3335588C2 (en) | 1998-12-17 |
GB2127839B (en) | 1986-02-19 |
DE3335588A1 (en) | 1984-04-05 |
GB8326335D0 (en) | 1983-11-02 |
JPH0696633B2 (en) | 1994-11-30 |
CA1224600A (en) | 1987-07-21 |
JPH03269013A (en) | 1991-11-29 |
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