CA1100370A - Absorbable coating composition for sutures - Google Patents

Abstract

ABSTRACT
The tie-down properties of ?ultifilamen? surgical sutures are improved by coating the suture with an absorbable composition comprising a mixture of from about 1 to 4 parts of an absorbable, film-forming polymer, and 1 to 4 parts of a substantially water-insoluble salt of a C6 or higher fa??y acid. Braided sutures coated with from 2 to 10 per cent by weight of the composition are characterized by a smooth knot tie-down under both wet and dry conditions.

Description

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1~0(~370 BAC~GROUND OF T~E INVENTION

Field of Invention This invention relates to an absorbable composition useful as a coating and lubricating finish for surgical sutures. More particularly, this invention reiates to a means for improving the tie-down properties of synthetic absorb-able multifilament sutures by coating tne sutures with an absorbable lubricating composition.

Description of Prior Art Suture materials are generally classified as either absorbable or non-absorbable, with each type of suture material being preferred for certain appiications. Absorb-~ble suture materials are preferred for internal wound repair in whic~h tne sewn tissues will hold together after healing lS without suture reinforcement and in which a non-absorbed suture may promote tissue irritation or other adverse bodily reaction over an extended period of time. Suture materials are considered to be absorbable if they disappear from the sewn tissue within about a year after surgery, but many absorbable su-ure materials disappear within shorter periods.
The earliest available absorbable suture materials were catgut and extruded collagenous materials. More recently, absorbable sutures derived from synthetic polymers ha~e been developed which are strong, dimensionally uniform, and storage-stable in the dry state. Typical of such polymers are lacti~ehomopolymers and copolymers of lactide and glycolide such as t~lose disclosed in United States Patent No. 3,636,956, and glycolide homopolymers sucn as those disclosed in Unitea 1~0~370 States Patent No. 3,565,869.
Monofilament synthetic absorbable suture materials are generally stiffer than their catgut or collagen counter-parts, and synthetic absorbable sutures are therefore usually employed in a multifilament, braided construction in order to provide the suture with the desired degree of softness and flexibility. Such multifilament sutures exhibit a cer-tain degree of undesirable roughness or Ugrabbiness'' in what has been termed their "tie-down~ performance, i.e., the ease or difficulty of sliding a knot down the suture into place.
Multifilament non-absorbable sutures such as braided ~utures of polyethylene terephthalate, for example, can be improved with respect to tie-down performance by coating the external surface of the suture with solid par-ticles of polytetrafluoroethylene and a binder resin as dis-closed in United States Patent No. 3,527,650. This proce-dure, however, is undesirable as applied to absorbable sutures because polytetrafluoroethylene is non-absorbable and sutures coated therewith would leave a polymer residue in the sewn tissue, after the suture had absorbed.
Multifilament, non-absorbable sutures can also be improved with respect to tie-down performance by coating them with a linear polyester ha~ing a molecular weight be-tween about 1,000 and about 15,000 and at least two carbon atoms between the ester linkages in the polymer chain as disclosed in United States Patent No. 3,942,532. This patent discloses that the aforementioned polyesters may also be used to coat absorbable synthetic sutures but does not consider that such coated sutures would not be totally ab-sorbable.

`B 3 The aforementioned U.S. patent number disclose~ that the synthetic absorbable sutures described therein may be coated with conventional suture coating materials such as a qilicone or beeswax in order to modify the handling or absorption rate of the sutures. These coating materials are not readily absorbable, however, and will accordingly leave an undesirable residue in the tissue after the suture itself is absorbed.
It is accordingly an object of the present inven-tion to provide an absorbable, lubricating coating for multi-filament sutures of braided, twisted or covered construction.
It is a further object of this invention to provide an ab-sorbable coating to improve the tie-down properties of such multifilament sutures. It is a yet further object of this invention to provide a wholly absorbable coated synthetic multifilament suture having good knot tie-down properties.
SUMMARY OF THE INVENTION
In accordance with the instant invention, there is provided as a coating for sutures, particularly synthetic absorbable multifilement sutures, an absorbable composition comprising a film-forming polymer and a substantially water-insoluble salt of a C6 or higher fatty acid. The coating is preferably applied to the suture from a solvent solution to provide a final coating add-on of from about 2 to 10 per cent by weight of the suture.
The film-forming polymer is preferably a copolymer of lactide and glycolide, while the fatty acid salt is pref-erably a calcium salt of a C6 to C2~ fatty acid. The ratio of polymer to fatty acid salt in the coating composition may be within the range of about 1:4 to 4:1 parts by weight.

The coating is particularly useful for improving the tie-down ~B 4 _ smoothness of braided sutures prepared from homopolymers and copolymers of lactide and glycolide, and other absorbable polymers.
In accordance with a broad aspect of the invention, there is provided a synthetic, absorbable multifilament suture, having improved tie-down properties. The suture is coated with from about 2 to 15 per cent by weight of a composition comprising a mixture of a substantially water-insoluble, absorbable salt of a C6 or higher fatty acid and an absorbable, film-forming polymer. The ratio of said fatty acid salt to the polymer is from about 1:4 to 4:1.
DESC~IPTION OF PREFERRED EMBODIME~T
~ ne coating compositions of the instant invention may be applied to any suture material where it is desired to improve fiber lubricity, suture tie-down characteristics, or the like. The coating is particularly useful with synthetic absorbable multifilament sutures such as polylactide, poly-glycolide copolymers of lactide and glycolide, poly(p-diox-anone), poly(alkylene oxalate), and mixtures of such poly-mers with each other and with other compatible absorbablecompositions as those described for example in United States Patent Nos. 3,636,~52 and 2,683,136. Preferred suture com-positions derived from lactide and glycolide are sometimes referred to herein as simply homopolymers and copolymers of lactide and glycolide.
In a preferred embodiment of the present invention, the coating is applied to the suture surface as a solu-tion and/or '.~

dispersion of the polymer and fatty acid salt in a volatile solvent such as acetone and solidification of the coating on the suture is accomplished by volatilizing the solvent. Tne coating may be applied to the suture by any suitable process such as passing the suture through a solution of the coating composition, or passed a brush or anplicator wetted with the solutionJ or passed one or more spray nozzles dispensing the solution as droplets. The suture wetted with the coating solution is subsequently passed through or held in a drying oven for a time and at a temperature sufficient to volatilize the solvent.
In place of a coating solution, the coating composi-tion may be applied as a melt of the constituents thereof, and in this case solidification takes place by cooling. The melt of the coating composition should, of course, be at a te~pe~ature below t`he melting temperature of the suture material, and this embodiment of the invention can be used only when the coating composition melts at relatively low temperatures.
The coating composition may also be applied to tne suture as a solid by passing the suture over or between solid ~locks of the coating composition which is then transferred to the surface of the suture by a rubbing action, possibly accompanied by localized melting.
In coating multifilament sutures with the compositions of this invention, it is not necessary that e~ery filament within the suture be individually or completely coated.

l~Q~'370 In most instances, howe~er, the coating composition will penetrate into the suture structure, particularly when the coating composition is applied as a solvent solution.
Suitable film formers useful in the coating compositions of this invention include homopolymers and co-polymers of lactide and glycolide, i.e., polylactide, poly-glycolide, and copolymers of lactide and glycolide with each other and with other reactive monomers; poly(~-dio~anone), poly(alkylene oxalate), copolymers of vinyl acetates with unsaturated carboxylic acids such as crotonic, acrylic, and methacrylic acids; water soluble or dispersible cellu-lose derivatives such as methyl cellulose, hydroxymethyl cellulose and carboxymethyl cellulose; natural gums; ethy-lene oxide polymers; polyacrylamide; colla~en; gelatin;
polyamino acids; polyvinyl alcohol; polyvinyl pyrrolidone;
absorbable conjugated unsaturated triglycerides such as dehydrated castor oil, and mixtures of such polymers.
Particularly preferred film-forming polymers are the copoly-mers of lactide and glycolide which contain from about 15 to ~5 per cent lactide, and have an inherent viscosity of from about 1.0 to 4.0 measured as a 0.1% solution in hexa-fl.loroisopropanol at 25C. These polymers are water-insoluble, rapidly absorbable, and soluble in many common organic solvents such as acetone, chloroform, toluene, xylene, and 1,1,2-trichloroethane which facilitates their applica-tion to the suture as solutions.

. llOG370 The fatty acid salts useful in the coating composi-tions of the present invention include the calcium, magnesium, barium, aluminum, and zinc salts of C6 and higher fatty acids, particularly those having from about 12 to 22 carbon atoms and mixtures thereof. The calcium salts of stearic, palmitic and oleic acids are particularly preferred for use in the present invention.
The ratio of the film-forming polymer and the fatty acid salt in the coating com~osition ma,~ vary depending upon t'le specific co~ponents selected and the particular suture being coated. In general, the preferred ratio of polymer to salt is within the range of 2:1 to 1:2 by weight, although useful compositions are obtained over a wider range of from about 1:4 to 4:1 parts by weight.
~ith sutures composed of homopolymers or copolymers of lactide and glycolide, the film former in the coating composition is preferably polylactide or a copolymer of lac-tide and glycolide containing at least about 15 per cent lactide, and preferably having different solubility charac-teristics than the suture. For example, a suture made of a lactide-glycolide copolymer containing about 10 per cent of dilactyl moieties mav be coated with a composition contain-ing, as a film former, a lactide-glycolide copolymer containing about ~5 per cent o~ dilactyl moieties, which copolymer is more readily soluble in com~on organic solvents than the suture material.
_~_ llU0370 The film former in the coating composition may, if desired, be the same composition as the suture provided that precautions are ta~en to avoid dissolving the suture when the coating composition is applied. This can be done by utilizing a coating composition in which the film former is a finely divided suspension in a non-solvent liquid, or by utilizing a coating co~position in which the film former is in solution at substantially saturation levels and the contact time of the suture with the coating composition is short before the solvent is driven off.
~ here the compositions of the suture and the film former are identical, and in other instances where the suture material may be subject to some surface dissolution and/or surface swelling or softening by reason of the action of the film former solvent thereon, there may be a gradual transition between the substrate composition and the coating composition rather than a sharp interface between them. There may also be some wea~ening of the suture accompanying the application of such coating compositions.
The coating composition may, if desired, also contain components other than those discussed above for other useful purposes including dyes, antibiotics, antiseptics, anesthetics and anti-inflammatory agents.
The amount of coating composition applied to the fiber, or the coating add-on, will vary depending upon the con-struction of the fiber, e.g., the nu~ber of filaments and tightness of braid or twist, and the nature of the coating _g_ material, e.g., melt, solution or solid. In general, the coating composition applied to a braid will constitute from about 5 to about 10 per cent by weight of the coated fiber, but coating composition add-on may range from as little as about two per cent by weight to as much as ~bout 15 per cent or higher in some ~ases. As a practical matter, and for reasons of econo~y and general performance, it is generally preferred to apply the minimum amount of coating composition consistent with good tie-down perfor~ance, and this level of add-on is readily determined exPerimentally for any ~articular fiber-coating system.
The improve~ent in tie-down properties ~mparted to synthetic absorbable sutures may be determined semi-quantitatively by comparing the feel of coated and uncoated sutures during the act of tying down a single throw knot.
Such comparisons are preferably made on both wet and dry sutures since many suture materials have different tie-down properties when tested wet or dry. Suture tie-down roughness is graded from 0 to 10 with 0 being comparable to an uncoated suture and 10 indicating no detectable roughness.
Suture tie-down properties are evaluated dry after the sutures have been conditioned ~or at least 2 days in a vacuum dryin~ oven at room temperature and 100 microns absolute pressure, and wet after being ~mmersed in water at 25C for 1 minute. Roughness values above 4 are considered acceptable, while values of 7 or hi~her are comparable to conventional silicon coated silk and are considered fully satisfactory.

1~0~370 The following examples are provided to further illustrate and demonstrate the method and product of the present invention. Unless otherwise stated, all parts and percentages are by weight.

Exam~le 1 Forty-fi~e parts of a low molecular weignt (~inh 1.5 in I~FIP) lactide/glycolide co~olymer [65 mol % L(-) - lactide and 35 mol % glycolide] and fortY-five parts of calcium stearate~ were placed in a porcelain pebble mill with ~10 parts of 1,1,2-trichloroethane. Dissolving of the lactide/glycolide copolymer and dispersion of the calcium stearate were accomplished simultaneously by milling the mixture for two days. The solution/dispersion (Brookfield viscosity of 218 CPS at 35C.) was then transferred to a suture c'oating bath. A size 3-0 braided suture of 90/10 (weight percent) glycolide/lactide copol~ymer was coated with the composition by passing the suture through the mixture while using a folded felt pad to wipe excess material from the suture as .t exited the coating bath. The suture was coated at a speed of ~ feet per minute which provided an immersion time of about 5 seconds in the coating bath. After passing through the coating bath and the felt wiping pads, the suture *Calcium stearate, a commercial food grade product con-sisting of about l/3 C16 ar.d 2/3 Clg fatty acid, with small amounts of C14 and C22 fatty acids.

110C~370 immediately entered a drying tower where enough solvent was removed to render the suture t~ck free by the time the first guide was contacted. Drying was completed by winding the coated braid on a spool and keepin~ it in vacuum at 100 `~
microns for two days. The coating solids pick-up was determined to be 5.3% of the uncoated braid. The suture was finished by winding the coated braid on an annealing rack under mild tension and heating 10 minutes at 110C.
Using afore described semi-quantitative smoothness-of-tie-down test, the coated braid in a single throw knot tie-down rated 8-9 dry, and 8 wet. The tensile strength of the coated braid was 9.9 lbs. under straight tension and 5.4 lbs. knotted, while in the uncoated control, tensiles were 9.9 lbs. and 5.8 lbs., respectively. Braided synthetic absorbable sutures coated in a similar manner were sterilized with ethylene oxide and i~planted in animals. After 21 days, the strength of the coated braid was the same as in the uncoated control, and absorption was almost complete at 90 days, indicating that the coating composition or method of application had no significant effect on suture tensile strength or absorbabiiity.

Example 2 ~ Using a coating solution/dispersion identical in composition to that in Example 1 e~.cept that ;otal solids were 6% rather than 10~, the glycolide/lactide braided suture was coated by the same method. After vacuum arying, 110(~370 the coating solids pick-up was found to be 2.9% based on the uncoated braid.
As in Example 1, the suture was finished by heating the dry coated braid on an annealing rack at 110C. for 10 minutes. After ethylene oxide sterilization, s~oothness-of-tie-down was 7 dry and 6 wet. Tensile strengths were 10 lbs. and 5.4 lbs. strai~ht ar.d knot, respectively.
Implantation in animals showed the same strength retained at 21 days as for the uncoated control. At 90 days post implantation, absorption was com~lete and tissue reaction was minimal throughout the test period.

Example 3 The procedure of Example 2 was repeated by coating a size 4-0 braided sut~re comprised of poly(~-dioxanone) polymer with the 6~/, solids coating solution/dispersion composition. The coating solids pick-up of about 4% based on the weight of the uncoated suture. After drying, suture tie-down was tested and rated as excellent, being comparable to standard waxed silk suture material.

Example 4 Twenty-five parts of a low molecular weight ( ~inh 1.5 in HFIP) lactide/glycolide copolymer [65 mol 7O L(-) lactide and 35 mol ~ glycolide3 and twenty-fi~e parts of magnesium s~earate were placed in a flask with 360 parts of 1,1,2-trichloroethane and 90 parts by weight of chloroform.

11(~e~370 Solution of the polymer and dispersion of the stearate were obtained by stirring the mixture for about one week, resulting in a mixture having Brookfield viscosity of 299 CPS.
Using the methods described in Example 1, the glycolide/lactide braided suture was coated, and drie~, and coating pick-up was determined to be 3.1% based on the uncoated suture. Using the smoothness-of-tie-down test described in Exam~le 1, the dry and wet both rated 4-5.

Example 5 Twenty-five parts of a low molecular weight ( ~inh 1.5 in HFIP) lactide/glycolide copolymer [65 mol % L(-) lactide and 35 mol % glycolide] and twenty-fivc parts of zinc stearate were placed in a flask with 360 parts of 1,1,2-trichloroethane and 90 parts by weight of chloroform.
Solution and dispersion were obtained as in Example 3 to yield a coating composition having a viscosity of 139 CPS.
Using the metllods described in Exa~ple 1, the glycolide/lactide braided suture was coated wi,h 6.1% of coating solids based on the uncoated suture. TJsing the smoothness-of-tie-down test, the dry suture rated 5 while the wet suture rated 4.

Example 6 Seven and one-half ~arts of the same lactide/
glycolide copolymer described in the above examples and seven and one-halr parts of calci-~m ~almltate were placed in a ~' 'lt-4~

11(~(~370 flask containing 108 parts of 1,1,2-trichloroethane and 27 parts of chloroform. The polymer and palmitate salt were dissolved and dispersed by stirring vigorously several days.
Using methods of application and finishing described in Example 1, the glcyolide/lactide braided suture was coated with the solution/dispersion, and after drving, was found to have picked u~ 5.4% coating solids.
Using the smoothness-of-tie-down test, the dry and wet sutures rated 8 and 7, respectively.

Example 7 Seven and one-half parts of the same lactide/glycolide copolymer described in the above examples and seven and one-half parts of calcium oleate were placed in a flask containing 108 parts of I,1,2-tric-nloroethane and 27 parts-of chloroform.
The polymer and oleate salt were dissolved and dispersed by stirring vigorously several days.
Using methods of application and finishing described in Example 1, the glycolide/lactide braided suture was coated with the solution/dispersion, and after drying, was found to have picked up 9.8% coating solids.
Using the smoothness-of-tie-down test, the dry and wet sutures rated 5-1/2 and 4-1/2, respectively.

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110(1370 Exam~le Calcium salts of C6 (caDroic), C~ (caprvlic), Clo (ca~ric), Cll (undecylenic) and Cl2 (lauric) fatty acids were ~repared and applied to the glycolide1lactide braided suture of Claim l. After drying, suture tie-do~n properties were found to be significantly improved over the uncoated suture material. Metal salts of C6 and higher saturated and unsaturated fatty acids are tl~us shown to be efficacious in the nractice of the present invention.

l~n~ile the foregoing s~ecification and exam~les nave be~n directed to coating absorbable ~ultifilament braided sutures, it will be readily appreciated that the coating may likewise be used with good results on absorbable monofila-ment sutures as well as on non-absorbable monofila~ent and multifilament sutures.
Non-absorbable sutures such as cotton, linen, silk, nvlon, polyeti~ylene terephthalate and ~olyolefins are normally coated with non-absorbable compositions. Polyolefins are usually of ~onofilament construction wnile cotton, linen, silk and polyester are usually of braided, t~isted or covered multifilament construction. ~hile there is usually no re~uirement that the coating on such sutures be absorbable, the composition of the instant invention may, nPvertheless, be used as a lubricating finisn for non-absorbable sutures if desired.
In the abo~Je examples, tl;e coating soiution was ap~lied to the final suture structure in order to-provide a lla~370 substantiall~ continuous coating on at least the outward-facing surfaces of the outer-most filaments of the braid.
It is understood, however, that the coating solution may be applied, if desired, to the individual filaments before they are formed into strands or to the individual strands before they are formed into strands or to t~e individual strands before they are formed into the final suture struc-ture. Also, while all the above examples were conducted with size 3-0 braided suture prepared fro~ a 90/lO weig~lt per cent glycolide/lactide copolymer, this was for the sake of convenience only, and invention is not limited as to suture size or composition but may be practiced for example with sutures from size 9-0 to size 2 and larger, and with other suture materials. The foregoing examples are intended to be merely illustrative, and many modifications and varia-tions thereof will be apparent to those skilled in the art.

Claims (23)

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The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:-

1. A synthetic, absorbable multifilament suture having improved tie-down properties, said suture being coated with from about 2 to 15 per cent by weight of a composition comprising a mixture of a substantially water-insoluble, absorbable salt of a C6 or higher fatty acid and an absorb-able, film-forming polymer, the ratio of said fatty acid salt to said polymer being from about 1:4 to 4:1.

2. A suture of Claim 1, wherein the fatty acid salt is the salt of calcium, magnesium, barium, aluminum, or zinc.

3. A suture of Claim 1, wherein said higher fatty acid is selected from the group consisting of C12 to C22 fatty acids and mixtures thereof.

4. A suture of Claim 3, wherein the fatty acid salt is the salt of calcium or magnesium.

5. A suture of Claim 4, wherein the fatty acid comprises a mixture of stearic and palmitic acid.

6. A suture of Claim 1, wherein said film-forming polymer is selected from the group consisting of homopolymers and copolymers of poly(?-dioxanone), poly(alkylene oxalate), lactide and glycolide, copolymers of vinyl acetate with unsaturated carboxylic acids, water soluble or dispersible cellulose derivatives, natural gums, ethylene oxide polymers, polyacrylamide, polyvinyl alcohol, polyvinyl pyrrolidone, gelatin, collagen, polyamino acids, conjugated unsaturated triglycerides, and mixtures thereof.

7. A suture of Claim 1, wherein said film-forming polymer is a copolymer of lactide and glycolide containing from about 15 to 85 mol per cent dilactyl units.

8. A suture of Claim 7, wherein said lactide/

glycolide copolymer has an inherent viscosity of from about 1.0 to 4.0 measured as a 0.1% solution in hexafluoroisopro-panol at 25°C.

9. A suture of Claim 8, wherein the lactide/glycolide copolymer contains about 65 mol per cent dilactyl units.

10. A suture of Claim 9, wherein the fatty acid salt comprises a mixture of calcium palmitate and calcium stearate.

11. A suture of Claim 10, wherein the ratio of the fatty acid salt to lactide/glycolide polymer is between about 1:2 and 2:1.

12. A suture of Claim 11, coated with. from about 5 to 10 per cent of the said mixture.

13. A suture of Claim 1, wherein the synthetic absorbable suture is comprised of homopolymers or copolymers of lactide and glycolide.

14. A suture of Claim 13, wherein said suture is comprised of a copolymer of 10 weight per cent lactide and 90 weight per cent glycolide.

15. A suture of Claim 14, wherein the multifila-ment suture is a braided suture.

16. A suture of Claim 1, wherein the synthetic absorbable suture is composed of poly(?-dioxanone).

17. A suture of Claim 16, wherein the multiflament suture is a braided suture.

18. A method for improving the tie-down characteristics of a multifilament suture which comprises coating said suture with from about 2 to 15 per cent by weight of a composition comprising a mixture of a substan-tially water-insoluble, absorbable salt of a C6 or higher fatty acid and an absorbable, film-forming polymer, the ratio of said fatty acid salt to said polymer being from about 1:4 to 4:1.

19. The method of Claim 18, wherein the fatty acid salt is the salt of calcium, magnesium, barium, aluminum, or zinc.

20. The method of Claim 18, wherein said nigher fatty acid is selected from the group consisting of C12 to C22 fatty acids and mixtures thereof.

21. The method of Claim 18, wherein said film-forming polymer is selected from the group consisting of homopolymers and copolymers of poly(?-dioxanone), poly(alky-lene oxalate), lactide and glycolide, copolymers of vinyl acetate with unsaturated carboxylic acids, water soluble or dispersible cellulose derivatives, natural gums, ethylene oxide polymers, polyacrylamide, polyvinyl alcohol, poly-vinyl pyrrolidone, gelatin, collagen, polyamino acids, conjugated unsaturated triglycerides, and mixtures thereof.

22. The method of Claim 18, wherein said suture is composed of an absorbable synthetic polymer selected from the group consisting of homopolymers and copolymers of lactide and glycolide.

23. The method of Claim 17, wherein said suture is composed of poly(?-dioxanone).