JPS6025974B2 - Absorbable coating composition for sutures - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides coatings for surgical sutures,
The present invention relates to absorbent compositions useful as finishing touches.

More particularly, the present invention relates to the tiedown properties of absorbable synthetic multifilament sutures.
es) by coating sewing sutures with an absorbable lubricating composition. Suture materials are generally classified as absorbable or non-absorbable, and each type of suture material is preferred for certain applications.

Absorbable suture materials tend to cause the sutured tissues to stick together after union without suture reinforcement and promote long-term tissue irritation or other adverse body reactions if non-absorbable sutures are used. Internalwo
uM) is favorable for recovery. Although a suture material is considered absorbable if it disappears from the sutured tissue within about a year after surgery, many absorbable suture materials disappear within a shorter period of time. The earliest available absorbable suture materials were catgut (ca = ut) and extruded collage skin (us) materials.

More recently, absorbable sutures based on synthetic polymers have been developed that are strong, dimensionally uniform, and storable in a dry state. Typical of such polymers are lactide homopolymers and copolymers of lactide and glycolide, such as those disclosed in U.S. Pat. No. 3,636,956;
and glycolide homopolymers as disclosed in US Pat. No. 3,565,86y, both of which are incorporated herein by reference. Absorbable synthetic monofilament suture materials are generally stronger than catgut or collagen suture materials, and therefore, absorbable synthetic sutures are usually made of multifilament material to give them the desired degree of softness and flexibility. braid
ed) used in the structure.

Such multifilament sutures have a certain degree of undesirable roughness in terms of their fineness performance, i.e. the ease or difficulty of sliding the suture knot into place. (rou axis ss) or graviness (scale abbi ss). A multifilament non-absorbable suture, such as a braided polyethylene terephthalate suture, may be prepared, for example, by coating the external surface of the suture with solid particles of polytetrafluoroethylene and a binder resin such as that disclosed in U.S. Pat. No. 3,527,65. Coatings can improve striping performance.

However, this treatment is undesirable for application to absorbable sutures. Polytetrafluoroethylene is non-absorbable, and sutures coated with it leave polymeric residue in the sutured tissue after the suture is absorbed. Multifilament, non-absorbable sutures have at least two carbon atoms between ester bonds in the polymer chains and about one
Subsequent performance may also be improved by coating them with a bran-like polyester having a molecular weight of from 1,000 to about 1,500 oz. This patent also discloses that the polyester can be used to coat absorbable synthetic sutures, but does not take into account that such coated sutures are not absorbable at all. The US patent discloses that the absorbable synthetic sutures described therein can be coated with conventional suture coating materials such as silicone or beeswax to improve the handling or absorption rate of the suture. ing. However, these covering materials are not easily absorbable and therefore the suture will absorb and leave an undesirable residue in the posterior tissues. Therefore, the purpose of the present invention is to
The object of the present invention is to provide an absorbent lubricious coating for multifilaments of braided, twisted or covered construction. It is a further object of the present invention to provide an absorbable coating to improve the tying properties of such multifilament sutures. It is a further object of the present invention to provide a fully absorbable coated synthetic multifilament suture with good knot-feedability. According to the invention, a film-forming polymer as a coating for a suture, especially an absorbable synthetic multifilament suture;
Absorbent compositions are provided comprising salts of C6 or higher fatty acids that are substantially insoluble in water.

The coating is preferably applied to the suture from a solvent solution to provide a final coating add-on of about 2-10% by weight of the suture. The film-forming polymer is preferably a copolymer of lactide and glycolide, while the fatty acid salt is preferably a calcium salt of a C6-C2 fatty acid.

The ratio of polymer to fatty acid salt in the coating composition is approximately 1:4 to 4.
:1 part by weight. The coating is particularly useful for improving the ligation smoothness of plaid sutures made from homopolymers and copolymers of lactide and glycolide and other absorbable polymers. The coating compositions of the present invention can be applied to any suture material where it is desired to improve fiber inertia, suture ligation properties, etc.

Coatings can be made of polylactide, polyglycolide copolymers of lactide and glycolide, poly(p-dioxanone), poly(alkylene oxide), and mixtures of such polymers with each other, as well as with such polymers, e.g., U.S. Pat.
No. 52 and No. 2 Iso 3136, both of which are incorporated herein by reference. Incorporate into. Preferred suture compositions derived from lactide and glycolide may be referred to herein simply as lactide and glycolide homopolymers and copolymers. In a preferred embodiment of the invention, the coating is applied to the suture surface as a solution and/or dispersion of the polymer and fatty acid salt in a volatile solvent such as acetone, and solidification of the coating on the surface evaporates the solvent. This is achieved by

The coating may be applied by any suitable process, such as by passing a solution of the coating composition through the suture, passing it through a brush or applicator moistened with the solution, or dispensing the solution as droplets. It can be applied to the suture by passing it through a spray nozzle. The suture wetted with the coating solution is then passed through or held in a dry open for a temperature and time sufficient to evaporate the solvent. Instead of a coating solution, the coating composition can be applied as a melt of its components, in which case solidification takes place on cooling.

The melt of the coating composition should, of course, be at a temperature below the melting temperature of the suture material, and this aspect of the invention can only be used when the coating composition melts at relatively low temperatures. The coating composition is applied to the suture as a solid by passing the suture between or over solid blocks of coating composition that later migrate to the surface of the suture by frictional action with optional local melting. It can also be applied.

In coating multifilament sutures with the compositions of the present invention, it is not necessary that all filaments within the suture be individually or completely coated.

However, in most instances, the coating composition will penetrate into the suture structure, especially when the coating composition is applied as a solvent solution. Suitable film formers useful in the coating compositions of the present invention include homopolymers and copolymers of lactide and glycolide, i.e. polylactide,
Polyglycolide and copolymers of lactide and glycolide with each other and with other reactive monomers; Copolymers with saturated carboxylic acids: water-soluble or water-dispersible monolithic cellulose derivatives such as methylcellulose, hydroxymethylcellulose and carboxymethylcellulose; natural rubber; ethylene oxide polymers; polyacrylamide;
Collagen; gelatin; polyamino acids; polyvinyl alcohol; polyvinylpyrrolidone: absorbable conjugated unsaturated triglycerides such as dehydrated castor oil and mixtures of such polymers. A particularly preferred film-forming polymer contains about 15% to 85% lactide and as a 0.1% solution in hexafluoroisopropanol,
It is a copolymer of lactide and glycolide having an inherent viscosity of about 1.0 to 4.0 as measured at 0. These polymers are insoluble in water, rapidly absorbable, and facilitate application to sutures as a solution in acetone, chloroform, toluene, xylene, and 1.1
- Soluble in many common organic solvents such as 2-trichloroethane. Fatty acid salts useful in the coating compositions of the present invention include C6 and higher fatty acids, especially about 12
Included are calcium, magnesium, barium, aluminum and zinc salts having up to 22 carbon atoms and mixtures thereof.

The calcium salts of stearic acid, palmitic acid and oleic acid are particularly preferred for use in the present invention. The proportions of film-forming polymer and fatty acids in the coating composition can vary depending on the particular components chosen and the particular suture to be coated. In general, preferred ratios of polymer to salt are from 2:1 to 1:2, although useful compositions are obtained over a wide range of about 1:4 to 4:1 parts by weight.
within the weight range. For sutures comprised of homopolymers or copolymers of lactide and glycolide, the film former in the coating composition preferably contains polylactide or at least about 15% lactide and is preferably different from the suture. It is a copolymer of lactide and glycolide with solubility properties.

For example, a suture made from a lactide-glycolide copolymer containing about 10% dilactyl content has a dilactyl content of about 65%, which is more readily soluble in common organic solvents than the suture material. The lactide-glycolide copolymer contained therein can be coated with a composition containing it as a film former. The film former in the present coating composition can optionally be of the same composition as the suture, provided that care is taken to avoid dissolving the suture when applying the coating composition. This can be done by using a coating composition in which the film former is a finely divided suspension in a non-solvent liquid, or by using a coating composition in which the film former is at a substantially saturated level in solution. coating composition, and the contact time between the coating composition and the suture is brief before the solvent is driven off. If the compositions of the suture and film former are the same, and in other cases the suture material may undergo some surface dissolution and/or surface swelling or softening due to the action of the film former solvent on it. In some cases, there may be a gradual transition between the substrate composition and the coating composition rather than a sharp interface.

There may also be some weakening of the suture with application of such coating compositions. The coating composition may optionally contain ingredients for other useful purposes in addition to the ingredients listed above, including dyes, antibiotics, preservatives, anesthetics, and anti-inflammatory agents. The amount of coating composition applied to the fibers, i.e. the coating pick-up, depends on the structure of the fibers, e.g. number of filaments and the tightness of braiding or twisting, and the nature of the coating material, e.g. whether it is a melt, solution or solid. , can be changed depending on.

Generally, the coating composition applied to braiding comprises about 5 to 1% by weight of the coated fibers, with coating composition pick-up ranging from about 15%, or in some cases higher, to about 2%.
% range. As a practical matter, and for reasons of economy and general performance, it is generally preferable to apply the minimum amount of coating composition consistent with good striping performance, and this impregnation level should be determined for any particular fiber coating system. can be easily determined experimentally. The improvement in ligation properties imparted to synthetic absorbable sutures was determined semi-quantitatively by comparing the tactile sensation of coated and uncoated sutures during the striping of a single throw knot. can be determined.

Such comparisons are preferably made for both wet and dry sutures since many suture materials have different tying properties when tested in wet or dry conditions. Suture roughness is graded from 0 to 10, with 0 corresponding to uncoated suture and 10 indicating undetectable roughness. The total knot triad is conditioned for at least two days at room temperature and 100 micron absolute pressure in a vacuum drying oven and wetted after soaking in water at 2500 for 1 minute.

Roughness values greater than 4 are considered acceptable, whereas values of 7 or greater correspond to conventional silicone-coated silk and are considered fully satisfactory.

The following examples further illustrate and illustrate the methods and products of this invention.

All parts and percentages are by weight unless otherwise specified.
Example 1 45 parts of a low molecular weight (inherent (1.5) in HFIP) lactide/glycolide copolymer [65 mol% 1(1)lactide and 35 mol% glycolide] and 45 parts of calcium stearate were mixed in 1.1.2- It was placed in a nutritious bevel mill with 81 particles of trichloroethane.

Calcium stearate, a commercially available food grade product lactide/glycolide copolymer consisting of approximately 1/6, 6 and 2/8 fatty acids along with small amounts of C, Z and C22 fatty acids, and dispersion of calcium stearate were added to the above mixture. 2
This was achieved by milling simultaneously for several days. The solution/dispersion (Prookfield viscosity of 21 mps at 3500) was then transferred to the suture overlay. A 90/10 [wt%] glycolide nolactide copolymer size 3-0 braided suture was prepared using a felt pad to wipe excess material from the suture as it exits the jacket. The above composition was coated by passing the mixture through the tube.

The suture was coated at a speed of 8 ft/min for approximately 5 min in the coating bath.
The bonding time was set to seconds. After passing through the jacket and felt wiping pad, the suture immediately entered a drying tower where sufficient solvent was removed to render the suture tack-free by the time the first guide was contacted. This was accomplished by winding the coated blade onto a spool and holding it in a 100 micron vacuum for two days. The coated solids coverage was determined to be 5.3% of the uncoated blade. The suture was finished by winding the coated braid onto an annealing rack under gentle tension and heating at 11,000 for 10 minutes. Using the semi-quantitative ligation smoothness test described above, the coated blades rated 8-9 dry and 8 wet in single throw knot feeding.

The tensile strength of the coated blade was 9.9 lbs. under linear tension and 5.4 lbs. in the knot, while for the uncoated control the tensile strength was 9.9 lbs. and 5.4 lbs., respectively.
It was 8 pounds. Similarly coated braided absorbable synthetic sutures were sterilized with ethylene oxide and implanted into animals. After 21 days, the strength of the coated blade was the same as the uncoated control, and absorption was nearly complete at 90 days, indicating that the coating composition or method of application had no effect on suture tensile strength or absorbency. Indicates that the effect is not significant enough to cause a problem.

Example 2 A glycolide/lactide braided suture was prepared in the same manner using a coating solution/dispersion of the same composition as in Example 1 except that the total solids content was 6% instead of 10%. coated.

After vacuum drying, the coating mass coverage was found to be 2.9% based on the uncoated blade. The dry coated blade was finished as in Example 1 by heating in an annealing rack at 110 qo for 10 minutes.

After ethylene oxide sterilization, the mackerel smoothness was 7 in the dry state and 6 in the wet state. The tensile strength was 10 pounds and 5.4 pounds in straight and knot tension, respectively. Transplantation in animals was similar to uncoated controls at 2
It was shown that the strength was maintained on the first day. After 90 days post-implantation, resorption was complete and tissue reaction was minimal throughout the study period.

Example 3 The process of Example 2 was repeated by coating a size 4-0 braided suture consisting of poly(p-dioxanone) polymer with a 6% solids coating solution/dispersion composition.

Coated solids coverage is approximately 4% based on the weight of the uncoated suture.
%Met. After drying, the suture quality was tested and rated as excellent, which is comparable to standard waxed silk suture material. Example 4 25 parts of a low molecular weight (inherent sword in HFIP 1.5) lactide/glycolide copolymer [65 mol% L(1)lactide and 35 mol% glycolide] and 25 parts of magnesium stearate were mixed with 1,112-trichloro Etan 36
0 parts and 90 parts by weight of chloroform into a flask.

A solution of the polymer and a dispersion of the stearate was obtained by concentrating the mixture for about one week, yielding a mixture with a Brookfield viscosity of 299 ps.

Using the method described in Example 1, a glycolide/lactide plated suture was coated and dried, and the coating coverage was determined to be 8.1% based on the uncoated suture.

Using the silk three smoothness test described in Example 1, both dry and wet were rated 4-5. Example
5 25 parts of a low molecular weight (injection in HFIP 1.5) lactide/glycolide copolymer [65 mol% L(1)lactide and 35 mol% glycolide] and 25 parts of zinc stearate were mixed into 1. It was placed in a flask together with 36 parts of 1,2-trichloroethane and 90 parts by weight of chloroform.

Solutions and dispersions were obtained as in Example 3.13
A coating composition with a viscosity of 9 ps was obtained. Example 1
Using the method described, coated solid glycolide/lactide braided sutures relative to uncoated sutures 6.1
Coated with %.

Using the Sabatsu Smoothness Test, the dry sutures came in with a rating of 5, while the wet sutures came in with a rating of 4. Example 6 The same lactide noglycolide copolymer 71/Moribe and calcium palmitate 71/Group part as described in the previous example
- Placed in a flask containing 108 parts of 1,2-trichloroethane and 27 parts of chloroform.

The polymer and palmitate were dissolved and dispersed by vigorous shaking for several days. Using the method of application and finishing described in Example 1, glycolide nolactide braided sutures were coated with the solution/dispersion and had a coverage of 5.5% after drying.
It was found to have a coating solids content of 4%.

Using the Precision Smoothness Test, the dry and wet sutures were rated 8 and 7, respectively.

Example 7 71/2 parts of the same lactide/glycolide copolymer and 71/2 parts of calcium stearate as described in the previous example
- 1,2-tIJ was placed in a flask containing 108 parts of chloroethane and 27 parts of chloroform.

The polymer and oleate salt were dissolved and dispersed by vigorous shaking for several days. Using the method of application and finishing described in Example 1, glycolide/lactide braided sutures were coated with the solution/dispersion and after drying, the coverage was 9.
．． It was found to have 8% solids coverage.

Using the knot lubricity test, the dry and wet sutures were rated 51/2 and 41/2, respectively.

Example 8 1C6 (Capron), C8 (Capryl), C,.

(Caplin), C,. Calcium salts of (undecylene) and C,2 (lauric) fatty acids were prepared and applied to the glycolide/lactide braided suture of claim 1. After drying, suture tieability was found to be significantly improved over uncoated suture material. Metal salts of C6 and higher saturated and unsaturated fatty acids are thus shown to be useful in the practice of this invention. Although the foregoing specification and examples have been directed to coating absorbable multifilament braided sutures, the present coating has shown good results for absorbable monofilament sutures and non-absorbable monofilament and multifilament sutures. can be used similarly. Non-absorbable sutures such as cotton, linen, silk, nylon, polyethylene terephthalate and polyolefins are commonly coated with non-absorbable compositions.

Polyolefins are usually of monofilament construction, while cotton, linen, silk and polyester are usually of braided, twisted or covered multifilament construction. While there is usually no requirement that the coating on such sutures be absorbable, the compositions of the present invention can nevertheless be used as a lubricious finish on non-absorbable synthetic threads, if desired. In the above examples, a coating solution was applied to the final suture structure to provide a substantially continuous coating on the outwardly facing surface of at least one of the outermost filaments of the plate.

Claims (1)

[Claims] 1 Contains a mixture of a substantially water-insoluble, absorbable salt of a C_6 or higher fatty acid and an absorbable, film-forming polymer, wherein the fatty acid salt and the polymer The ratio is about 1:
An absorbable synthetic multifilament suture having improved ligation properties characterized by being coated with about 2-15% by weight of a composition that is 4-4:1. 2. The suture according to claim 1, wherein the fatty acid salt is a calcium, magnesium, barium or zinc salt. 3. The suture according to claim 1, wherein the higher fatty acid is selected from the group consisting of C_1_2 to C_2_2 fatty acids and mixtures thereof. 4. The suture according to claim 3, wherein the fatty acid salt is a calcium or magnesium salt. 5. The suture of claim 4, wherein the fatty acid comprises a mixture of stearic acid and palmitic acid. 6. The film-forming polymer is poly(p-dioxanone), poly(alkylene oxalate), homopolymers and copolymers of lactide and glycolide, copolymers of vinyl acetate and unsaturated carboxylic acids, water-soluble or Dispersible cellulose derivatives, natural rubber, ethylene oxide polymers,
Polyacrylamide, polyvinyl alcohol, polyvinylpyrrolidone, gelatin, collagen, polyamino acids,
The suture of claim 1, wherein the suture is selected from the group consisting of conjugated unsaturated triglycerides, and mixtures thereof. 7. The suture of claim 1, wherein said film-forming polymer is a copolymer of lactide and glycolide containing about 15 to 85 mole percent dilactyl units. 8. The suture of claim 7, wherein said lactide/glycolide copolymer has an inherent viscosity of about 1.0 to 4.0 as measured at 25°C as a 0.1% solution in hexafluoroisopropanol. thread. 9. The suture of claim 8, wherein the lactide/glycolide copolymer contains about 65 mole percent dilactyl units. 10 Claim 9, wherein the fatty acid salt comprises a mixture of calcium palmitate and calcium stearate.
Sutures as described in section. 11. The suture of claim 10, wherein the ratio of said fatty acid salt to lactide/glycolide polymer is between about 1:2 and 2:1. 12. The suture of claim 11 coated with about 5-10% of said mixture. 13. Claim 1, wherein the absorbable synthetic suture comprises a homopolymer or copolymer of lactide and glycolide.
Sutures as described in section. 14. The suture of claim 13, wherein the suture is a copolymer of 10% by weight lactide and 90% by weight glycolide. 15. The suture of claim 14, wherein the multifilament suture is a braided suture. 16 The absorbable synthetic suture is poly(p-dioxanone)
A suture according to claim 1, comprising: 17. The suture of claim 16, wherein the multifilament suture is a braided suture. Contains a mixture of a substantially insoluble, absorbable salt of a 18 C_6 or higher fatty acid and an absorbable, film-forming polymer, the ratio of fatty acid salt to polymer being about 1
:4 to 4:1, the coating comprises a solution and/or dispersion of the composition in a volatile solvent. A method for producing an absorbable synthetic multifilament suture, characterized in that it is applied as a solid, either as a melt or as a solid by passing the suture between or over solid blocks. 19. The method according to claim 18, wherein the fatty acid salt is a calcium, magnesium, barium, aluminum or zinc salt. 20. The method of claim 18, wherein the higher fatty acid is selected from the group consisting of C_1_2 to C_2_2 fatty acids and mixtures thereof. 21 The film-forming polymer is poly(p-dioxanone), poly(alkylene oxalate), homopolymers and copolymers of lactide and glycolide, copolymers of vinyl acetate and unsaturated carboxylic acids, water-soluble or dispersible cellulose derivatives, natural rubber, ethylene oxide polymers, polyacrylamide, polyvinyl alcohol, polyvinylpyrrolidone, gelatin, collagen, polyamino acids, conjugated unsaturated triglycerides, and mixtures thereof. range 18th
The method described in section. 22. The method of claim 18, wherein the suture comprises an absorbable synthetic polymer selected from the group consisting of lactide and glycolide homopolymers and copolymers. 23. The method of claim 18, wherein the suture comprises poly(p-dioxanone).