CA1310917C

CA1310917C - Bioabsorbable coating for a surgical article

Info

Publication number: CA1310917C
Application number: CA000547352A
Authority: CA
Inventors: Peter Kendrick Jarrett; Donald James Casey; Leonard Theodore Lehmann
Original assignee: American Cyanamid Co
Current assignee: Covidien AG
Priority date: 1986-09-23
Filing date: 1987-09-21
Publication date: 1992-12-01
Anticipated expiration: 2009-12-01
Also published as: IL83799A; IL83799A0; FI874127A0; JP2517731B2; JPS63145661A; AU602724B2; NO873950L; NO873950D0; AU7883387A; GR3007913T3; FI90943B; FI874127A; HK67795A; KR960014021B1; DE3785716T2; ES2040719T3; JPH08229111A; JP2689411B2; ZA877124B; DK495787D0

Abstract

30,471 Title: BIOABSORBABLE COATING FOR A SURGICAL ARTICLE

ABSTRACT
A bioabsorbable coating for a surgical article comprises a polymer manufactured from at least the monomer caprolactone. The surgical article can be a bioabsorbable suture or ligature.

Description

1310~17 BIOABSORBABLE COATING FOR A SURGICAL ARTICLE
A bioabsorbable coating for a surgical article comprises a polymer manufactured from at least the monomer caprolactone.
The surgical article can be a bioabsorbable suture or ligature.
The bioabsorbable coating of this invention has advantages over prior art polymers used with surgical sutures or ligatures. Specifically, sutures coated with the polymer coating of this invention are less stiff than sutures using a coating described in the prior art.
Also, the process for coating a bioabsorbable surgical article are not clearly described in the prior art. That is, the process of this invention uses a copolymer manufactured from at least the monomer caprolactone, which is soluble in acetone. A
prior art process can use a copolymer of lactide and glycolide, which may not be soluble in acetone.
The bioabsorbable coating of this invention has superior and unexpected properties over a known commercially available surgical suture or ligature coating. For example, the coating of this invention does not present a hazy appearance on a suture.
The coating can be dissolved in acetone which seems to be less deleterious than other known solvents, for example, methylene chloride. Further suture characteristics such as knot snug-in or repositionlng, knot security, and tissue drag appear to be equal to, if not better than, suture coatings disclosed in the prlor art.

L~.

According to the present invention there is provided a surgical articl~ having improved knot repositioning characterlstics, the article comprising a multifilamentary strand, the strand having a bioabsorbable coating, the coating comprising a block copolymer haYing one or more A blocks solely manufactured from the monomer caprolactone, and one or more ~ blocks manufactured from the monomer caprolactone randomly copolymerized with one or more monomers selected from the group conslsting of lactides, carbonates and a lactone other than caprolactone, the total caprolactone linkages in the copolymer belng more than 50 to about 85 percent by weight of said copolymer.

1310ql7 In preferred embodimen~s, the inherent viscosity of the random or block copolymer is up to about 1.0 dl/g (0.5 g/dl in C~Cl3, 30C).
The surgieal artlcle eoated with the above deseribed polymers can be bioabsorbable. In one embodiment, the invention ls a eoating in combination with a bioabsorbable suture or ligature. In a speeific embodiment, the suture or ligature is manufaetured from a polymer prepared from one or more monomers selected from the group eonsisting of laetide, carbonates and laetones.
In a more speelfic embodiment, the suture or ligature is manufactured from a homopolymer prepared from the monomer glycollde or from a copolymer prepared from the monomers glycolide and either or both 1,3-dloxan-2-one and lactide.
The eoating in combination with the suture or ligature can be in multifilamentary form. In a speeifle embodlment, the eoating eomprises about 1/10 to 5% by weight of the eoated multlfilamentary suture or llgature. In a more speelfie embodlment, the eoatlng eomprises about 1/2 to 3% by welght of the eoated multlfllamentary suture or ligature. In the more speeific embodiment, the coating can eomprise up to about 1 ~ percent by weight of the coated multifilamentary suture or ligature.

t ~t ~ 7 A process for manufacturing a coating in comblnation wlth a bioabsorbable surgical article comprises dissolving in acetone a block copolymer having a fir3t block manufactured from the monomer caprolactone and a second block manufacture~ from one or more monomers selected from the group consisting of lactides, carbonates and a lactone other than caprolactone, preferably dl-lactlde and 1,3-dioxan-2-one; contacting the surgical article with the dissolved copolymer; maintaining the contact between the surgical article and dissolved copolymer until the copolymer on the article preferably comprises from about 1/10 to 5~ by weight of the coated surgical article; removing the coated surgical article from the dissolved copolymer; and drying the copolymer coatlng on the surgical article. In one embodiment, the caprolactone is ~-caprolactone.
Descri~tion of the Preferred Embodimentls) The followlng examples descrlbe the best mode of making and using the polymers manufactured from at least the monomer caprolactone of this invention. Unless otherwise specified, all of the inherent viscosity measurements in the examples were conducted at 30C.

~rq _ 5 _ 1 31 09l 7 ~-Caprolactone Homopolymer A sample of ~-caprolactone homopolymer was purchased from Scientific Polymer Products, Inc. The sample ~nh was measured as 0.27 dl/g (0.5 g/dl in CHC13). GPC analysis in CH2C12 using polystyrene standards gave MW = 17,600 and MN =
8500.

Synthesis of ~-Caprolactone Homopolymer ~-Caprolactone (lOg, 0.088 mole), lauryl alcohol (0.122g, 6.57 x 10-4 mole) and stannous chloride dihydrate (0.988 mg, 4.38 x 10-6 mole) were combined in a flask. The flask was flushed with nitrogen and evacuated. The flask was heated at 135c in an oil bath for 24 hours. The resulting polymer had an ~inh of 0.53 dl/g (0.5 g/dl in HFAS). GPC
analysis in CH2C12 using polystyrene standards gave MW =
65,200 and MN = 26,900.

Synthesis of ~-Caprolactone-l-Lactide Copoly~er ~-Caprolactone (212.5g, 1.86 mole), l-lactide (37.5 g, 0.31 mole), lauryl alcohol (4.10 ml, 0.018 mole) and stannous chloride dihydrate (35.9 mg, 1.59 x 10-4 mole) were combined in a stirred reactor under nitrogen at 175C. The mixture was stirred at 175C for 3 hours. The resulting polymer had a composition, as determined by H'NMR, of 84 wt. % ~-caprolactone and 16 wt. % l-lactide. The inherent viscosity of the copolymer was 0.50 dl/g (0.5 g/dl in CHC13).

Synthesis of ~-Caprolactone-l-Lactide Copolymer ~-Caprolactone (30.0 g, 0.26 mole), l-lactide (170.0g, 1.18 mole), lauryl alcohol (5.10 g, 2.74 x 10-2 mole) and stannous chloride dihydrate (0.0162 g, 7.2 x 10-5 mole) were combined in a stirred reactor under nitrogen at 1800C. The mixture was stirred at 180C for 3 hours. The resulting polymer had a composition, as determined by H'NMR, of 13 wt.
%~-caprolactone and 87 wt. % l-lactide. The ~inh was 0.27 dl/g (0.5 g/dl in CHC13).

t 3 1 09 1 7 Synthesis of -Caprolactone-Trimethylene Carbonate Copolymer ~ -Caprolactone (8.0 g, 0.070 mole), trimethylene carbonate (2.0 g, 0.020 mole), lauryl alcohol (0.283 g, 1.52 x 10-3 mole) and stannous chloride dihydrate (2.02 mg, 8.91 x 10-6 mole) were combined in a flask. The flask was flushed with nitrogen, evacuated and sealed. The flask was heated at 135C for 24 hours. The resulting polymer had a composition, as measured by H'NMR, of 86 wt. % ~-caprolactone and 14 wt.%
trimethylene carbonate. The ~inh of the copolymer was 0.26 dl/g (0.5 g/dl in HFAS).

Synthesis of ~-Caprolactone-Trimethylene Carbonate Copolymer ~-Caprolactone (40 g, 0.35 mole), trimethylene carbonate (10 g, 0.098 mole), lauryl alcohol (1.42 g, 5.4 x 10-3 mole) and stannous chloride dihydrate (10.1 mg, 4.5 x 10-5 mole) were combined in a flask and heated for 24 hours.under nitrogen at 135C. The resulting polymer had an inherent viscosity of 0.42 dl/g (0.5 g/dl in HFAS). The composition was determined by H'NMR to be 86 wt. %
caprolactone and 14 wt. % trimethylene carbonate.

Synthesis of ~-Caprolactone-Glycolide Copolymer ~-Caprolactone (170 g, 1.49 mole), glycolide (30 g, 0.26 mole), lauryl alcohol (1.37 g, 7.3 x 10-3 mole) and stannous octoate (0.052 g, 1.2 x 10-4 mole) were combined in a stirred reactor under nitrogen at 180C. The mixture was stirred at 18~C for 4.5 hours. The resulting polymer had an inherent viscosity of 0.68 dl/g (0.5 g/dl in CHC13). The composition was determined by H'NMR to be 85 wt~ % ~-capro-lactone and 15 wt. /O glycolide.

Synthesis of ~-Caprolactone-Glycolide Copolymers A series of ~-caprolactone-glycolide copolymers was prepared by the general procedure described in Example 7.
Specific preparative details and properties of the resulting polymers are summarized in Table 1.

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Synthesis of -Caprolactone-(Glycolide-Trimethylene Carbonate) AB Block Copolymer Glycolide (78 g, 0.572 mole), trimethyl-ene carbonate (52 g, 0.509 mole), lauryl alcohol (1.336 g, 7.17 x 10-3 mole) and stannous octoate (19.0 mg, 4.48 x 10-5 mole) were combined in a stirred reactor at 181C. The mixture was stirred at 181C. to 184C. for 2.5 hours. -caprolactone (70 g, 0.613 mole) was then added. The mixture was stirred at 183C. to 184C. for 4.0 hours. The resulting copolymer ~nh was 0.57 dl/g (0.5 g/dl in CHC13).
The composition, as measured by H'NMR, was 34 wt % -caprolactone, 41% glycolide, and 25 wt % trimethylene carbonate.

Synthesis of -Caprolactone-(Glycolide-Trimethylene Carbonate AB Block Copolymer Glycolide (90 g, 0.775 mole), trimethyl-ene carbonate (60 g, 0.588 mole), lauryl alcohol (0.336 g, 1.80 x 10-3 mole~ and stannous octoate (19.2 mg, 4.52 x 10-5 mole) were combined in a stirred reactor at 181 C. The mixture was stirred at 183C. to 184C. for 2.5 hours. -caprolactone (70 g, 0.613 mole) was then added. The mixture was stirred at 186C. for 4.0 hours. The resulting copolymer ~nh was 0.63 dl/g (0.5 g/dl in CHC13). The composition, as measured by H'NMR, was 22 wt. % -CaprO-lactone, 48% glycolide, and 30 wt % trimethylene carbonate.
EXAMPLE l_ 5ynthesis of -Caprolactone-l-Lactide AB Block Copolymer -Caprolactone (95 g, 0.482 mole), lauryl alcohol (0.148 g, 7.92 x 10-4 mole) and stannous chloride dihydrate (7.19 mg, 3.19 x 10-4 mole) were combined in a -- 1 o --stirred reac~or at 154C. The mixture was stirred for 2 hours at 162C. to 172C. l-Lactide (83 g, 0.58 mole) was added and the temperature was gradually increased to 220C.
The mixture was stirred for 1 hour. More l-Lactide (77 g, 0.53 mole) was added. The mixture was stirred for 1 hour.
The resulting copolymer ~inh was 1.15 dl/g (0.5 g/dl in HFAS). The composition, as measured by H'NMR was 27 wt.
% caprolactone and 73 wt. % l-Lactide.

Synthesis of ~-Caprolactone-l-Lactide AB Block Copoly~er ~-Caprolactone (112 g, 0.98 mole), lauryl alcohol (0.193 mgl, 8.5 x 10-4 mole) and stan~ous chloride dihydrate (10.15 mg, 8.5 x 10-5 mole) were combined in a stirred reactor at 162C. The mixture was stirred at 162C. for 6 hours. The temperature was increased to 180C. and 16 g of l-Lactide was added (0.11 mole). The temperature was gradually increased to 220C. over 1 hour and then 84 g l-Lactide was added. The mixture was stirred for 45 min. The resulting polymer had an inherent vis-cosity of 1.26 dl/g (0.5 g/dl in HFAS). The composition was determined by H'NMR to be 53 wt. % caprolactone and 47 wt. % l-lactide.

Synthesis of ~-Caprolactone-l-Lactide ABA Block Copolymer ~-Caprolactone (95 g, 0.482 mole), di-ethylene glycol (0.201 g, 1.90 x 10-3 mole) and stannous chloride dihydrate (7.19 mg, 3.19 x 10-4 mole) were com-bined in a stirred reactor at 154C. The mixture was stirred for 2 hours at 162C. to 172C. l-Lactide (20 g, 0.14 mole) and stannous chloride dihydrate (7.14 mg, 3.19 x 10-4 mole) were added and the temperature was gradually increased to 220C. The mixture was stirred for 0.5 hours.
More l-Lactide (140 g, 0.97 mole) was added. The mixture - 11- 1310ql7 was stirred for 1 hour. The resulting copolymer ~inh was 1.29 dl/g (0.5 g/dl in HFAS). The composition, as measured by H'NMR was 26 wt. % caprolactone and 74 wt. % l-Lactide.
Table 2 summarizes the _ vitro performance for the bioabsorbable coatings of this invention.

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TABL~ 2 FOOTNOTFS
-(1) The coatings were applied to 1/0 polyglycolic acid braid from a 2~/o (wt/vol.) solution of the coating material dissolved in acetone (all random copolymers) or methyl-ene chloride (all block copolymers). Single integer pick-up valves are rounded off to the nearest whole number.
(2) This test measures the ability of a suture to be snugged-in. A loop is passed around a steel rod and tied with a square knot. The knot is set to a prescribed tension with an Instron tester, and the tension is then removed.
After resetting the gage length, the loop is tested to break. The breaking strength of the loop and elongation-to-break are recorded. The material elongation at the point of knot break is determined separately in a straight pull test and subtracted from the knot breaking elongation to obtain the slippage in mm within the knot up to the breaking point. Samples were tested immediately after 30 seconds immersion in saline solution (0.9% NaCl in distilled water).
The tensions used to set the knots, and all the other conditions of knot tying and testing, are practical laboratory conditions, but may not correspond to actual surgical practice. The knot snug-in may not correlate with clinical experience.

(3) A strand is tied to itself to form a loop, ~'ne knot is set to a prescribed tension, the loop is cut, and .'ne cut ends are clatllped in the jaws of an Instron tester. The breaking strength and elongation-to-break are measured.
The maximum slippa~e is rqcorded for the knots that break. This is defined as the difference between the average elongation-to-break of the knotted suture and the average elongation of an unknotted strand, measured at a load equal to the knot breaking strength. Samples are tested immediately after 30 seconds immersion in saline solution.

(4) Square knots were formed in hand-dipped 1/0 polyglycolic acid braid using a conventional suture tying board. The knot was then run down to the board to assess the stick-slipping of the knot (chatter) as it runr down and to assess the force required to initiate and sustain the run-down. The abbreviations are: R, Runs; L, Lock; RC, Runs with Chatter; RD, Runs with Difficulty; RU, Runs with Unredictability; RW, Runs Well. The comparisons are made on dry suture and on suture wet with saline.

(5) Knot does not hold.

' Table 3 summarizes the in vivo performance for some of the bioabsorbable coatings of this invention.

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18- 13~0917 (1) Coated, needled and sterilized sutures were tested in dogs.
(2) The coatings were applied to 1/0 polyglycolic acid braid from a 2% (wt/vol) solution of the coating material dissolved in acetone.
(3) A suture coated with the test material i5 passed through two sides of a wound in the animal. A square knot is formed in the suture approximately 12-15 mm from the final knot position required to close the wound. The two ends of the suture are then pulled to slide the knot into position. Knots that slide properly are rated 1 while knots that fail to move into position are rated 0. The rating for a coating is the sum of the "1" ratings divided by the total number of test specimens.
(4) Immediate knot security is determined by using a pair of curved tweezers to tug at the 8 to 10 mm length of the ears of a square knot with two additional throws. Knots that are secure when manipulated are rated 1, knots with a loose top throw are rated 2, knots with an open top throw are rated 3, and knots that are not secure when manipulated are rated 4. The number of knots falling into each category is then divided by the total number of test specimens to provide a rating in each category.

Claims

1. A surgical article having improved knot repositioning characteristics, the article comprising a multifilamentary strand, the strand having a bioabsorbable coating, the coating comprising a block copolymer having one or more A blocks solely manufactured from the monomer caprolactone, and one or more B blocks manufactured from the monomer caprolactone randomly copolymerized with one or more monomers selected from the group consisting of lactides, carbonates and a lactone other than caprolactone, the total caprolactone linkages in the copolymer being more than 50 to about 85 percent by weight of said copolymer.

2. An article of claim 1 wherein the caprolactone is .epsilon.-caprolactone.

3. An article of claim 1 wherein the one or more B blocks are manufactured from caprolactone and glycolide.

4. An article of claim 3 wherein the glycolide in the one or more B blocks comprises up to 50 percent by weight of the copolymer.

5. An article of claim 1 wherein the inherent viscosity of the copolymer is up to 1.0 dl/g (0.5 g/dl in CHCl3, 30°C).

6. An article of claim 1 wherein the surgical article is bioabsorbable.

7. An article of claim 6 wherein the bioabsorbable surgical article is a suture or ligature.

8. An article of claim 7 wherein the suture or ligature is manufactured from a polymer prepared from one or more monomers selected from the group consisting of lactides, carbonates and lactones.

9. An article of claim 8 wherein the suture or ligature is manufactured from a homopolymer prepared from the monomer glycolide.

10. An article of claim 8 wherein the suture or ligature is manufactured from a polymer prepared from at least the monomer lactide.

11. An article of claim 8 wherein the suture or ligature is manufactured from a copolymer prepared from the monomers glycolide and 1,3-dioxan-2-one.

12. An article of claim 10 wherein the suture or ligature is manufactured from a copolymer prepared from the monomers glycolide and lactide.

13. An article of claim 8 or 10 wherein the coating comprises about 1/10 to 5% by weight of the coated suture or ligature.

14. An article of claim 13 wherein the coating comprises about 1/4 to 3% by weight of the coated suture or ligature.