KR0139124B1 - Suture coating material - Google Patents

Abstract

The present invention relates to a surgical suture coating, characterized in that the surgical suture is coated with a thermoplastic biodegradable hydrogel (TBH) alone, or coated with a coating composition containing 20% by weight or more of TBH.

Description

Surgical Suture Coatings

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a surgical suture coating agent having improved surface sliding characteristics such as biotissue permeability and knot safety.

In surgical operations, various sutures are used to suture tissues such as blood vessels, intestines, and blood. Surgical sutures are monofilament and multifilament shaped structures, but in most cases they have a braided multifilament shaped structure. However, when the surgical suture is used without the surface coated, the tissue may be damaged by friction with the tissue during passage or fixation after knot. Various coatings are applied to the surgical suture to prevent this, or to slide the suture knot to a desired position.

Conventionally, as a coating of synthetic absorbent sutures, US Pat. No. 4,047,533 uses a polyoxyethylene-polyoxypropylene copolymer lubricant as a suture coating agent, but because it is performed under a wet state with water and blood during actual surgery. Since the coating agent is water-soluble, there is no slippery property, and thus the procedure is inconvenient. In addition, U.S. Patent No. 4,716,203 synthesized a double block copolymer or a triple block copolymer and developed it as a suture coating agent, but the copolymer was made of a polyalkalene oxide, polyglycolic acid or trimethylene carbonate bond, and used in vivo. There is a drawback that includes this suspicious alkylene oxide and does not include bonds that can be readily degraded in vivo, such as amide bonds.

The above-mentioned cases have no amide bonds that can be easily degraded by enzymes in vivo, and most of them use high molecular weight polyethylene glycol, and include substances which may be problematic for in vivo use, and are usually polylactide / polyethylene It has been directed to oxide / polylactide type block copolymers. In order to solve these problems, the present inventors have synthesized a thermoplastic biodegradable hydrogel (hereinafter abbreviated as TBH) that has high molecular weight and can be used in vivo, and used as a suture coating agent.

Referring to TBH newly used in the present invention in detail.

The present inventors have a high molecular weight, no chemical crosslinking, and are easy to process, and can be used in vivo, and are hydrophilic non-degradable polymers represented by general formulas (I) a to (I) f having the following structures (A ---). Multiblock thermoplastic biodegradable hydrogel (TBH) consisting of blocks and hydrophobic biodegradable polymer (B ---) blocks was used as suture coating.

Wherein A (-) is a hydrophilic non-degradable polymer such as polyethylene oxide (PEO) or polyethylene oxide / polypropylene oxide copolymer, and (B ---) is polylactide (PLA), polyglycolide (PGA) ), Hydrophobic biodegradable polymers such as PLA / PGA copolymer, polycaprolactone (PCL), polyorthoesters, polyanhydrides, and X is a chemical that degrades in vivo, such as amide bonds, ester bonds, and carbonate bonds. Y is a chemical bond that connects A and B or B such as amide bond, ester bond, carbonate bond by covalent bond, n is an integer from 0 to 10, q is an integer of 3 or 4 .

The method for synthesizing the biodegradable hydrogel is disclosed in Korean Patent Application No. 94-10696 of biodegradable hydrogel polymer of May 17, 1994 of the present inventors.

As the hydrophilic non-degradable polymer, a molecular weight of 600 to 30,000 polyethylene oxide (PEO) or polyethylene oxide polypropylene oxide copolymer is used, and a molecular weight of 2,000 to 10,000 is more preferable. When the low molecular weight of 2,000 or less is used, the flexibility and processability of the polymer is inferior, and when the molecular weight of 10,000 or more is used, the excretion through elongation has been difficult.

Therefore, in order to solve this problem, we have synthesized a high molecular weight polyethylene glycol having such characteristics in place of high molecular weight PEG, which is difficult for extracorporeal metabolism, to complete a polymer having improved processability. In other words, the biodegradable lactide or glycolide was polymerized on the sock terminal of the polyethylene polymer having a suitable molecular weight, and then polymerized with ethylene oxide to synthesize a hydrophilic polymer block (X-—) having a biodegradable bond. The synthesized block (X ---) part is completely different from the simple low molecular weight polyethylene glycol, and can be decomposed into low molecular weight PEG that can be metabolized in vitro by biodegradation while having high molecular weight PEG properties. This completes the (X-) part with the high molecular weight PEG properties we desire.

In addition, the hydrophobic moiety (----) polymer block is made of polylactide (PLA), polyglycolide (PGA), polycaprolactone (PCL), or copolymers thereof. Y) yielded a polymer having various numbers of branches.

Among the multiblock biodegradable hydrogels of the present invention having such a configuration, preferred multiblock copolymers including PEO, PLA, PGA and PCL are represented by the following structural formulas (I) and (I ′).

[HO (CH ₂ ) _Z- (OCHR ₁ COOCHR ₂ CO) m] ℓ-YA-Y '-[(COCHR ₁ OC (= O) CHR ₂ O) mO (CH ₂ ) _Z -H] ℓ (I)

[HO (CH ₂ ) _Z- (O (CH ₂ ) ₅ COm] ℓ-YA-Y '-[(CO (CH ₂ ) ₅ O) mO (CH ₂ ) _Z -H] ℓ (I')

Wherein A is a multiblock composed of hydrophilic and hydrophobic polymers, [(CH ₂ CH ₂ O) _n -X- (OCH ₂ CH ₂ ) _n ] _r , and X is -O (COCH ₂ O) _x -,- [COCH (CH ₃ ) O] _x −, Y is CH _y NHCO—, Y ′ is —CONHCH _y −, and R ₁ and R ₂ are hydrogen atoms or methyl groups.

x is an integer from 1 to 10 and z is an integer from 1 to 5.

y is 0, 1, or 2, where l has a value of 3, 2, or 1, respectively.

m is an integer from 1 to 100 and n is an integer from 20 to 500.

k is an integer from 0 to 10, and r is an integer from 0 to 10.

On the other hand, the number average molecular weight distribution of TBH obtained at this time was 5,000-50,000, Preferably it was 10,000-30,000, More preferably, it was 12,000-15,000.

Accordingly, the present inventors have found that by coating TBH on a surgical suture, a surgical suture having excellent surface slipping characteristics such as excellent knot stability and tissue permeability when wet has been found and reached the present invention. That is, the present invention is a surgical suture whose surface is coated with TBH itself or a composition containing one such TBH, and a surgical suture with improved surface sliding characteristics.

In the present invention, TBH itself may be coated on the filament alone, or may be used as one component of a coating composition composed of a mixture of multiple components. In the composition containing at least one of TBH, as another component, a bioabsorbable polymer, for example, a glycolide and / or a lactide polymer, a polyglycolide, a polylactide or a copolymer of glycolide and lactide, and polycapro Preference is given to using lactones.

The suture material may be a bioabsorbable polymer such as polyglycolide, polylactide or glycolide-lactide copolymer, other glycolide-caprolactone copolymer, polyhydroxybutyl acid, poly-p-di It is preferable that oxane consists of trimethylene carbonate copolymer.

The surgical suture of the present invention may be coated with TBH as it is, and the surgical suture is immersed in a solution in which TBH and other bioabsorbable polymers are dissolved in a volatile solvent, and the coating amount is 0.1 to 100 parts by weight of the suture. It may be prepared by coating the solvent to about 20 parts by weight to volatilize the solvent. In addition, in the present invention, the coating is not necessarily completely covered with the suture, and the coating agent may be partially covered or adhered to the surface of the filament in spots or spots.

In the present invention, the surgical suture may be bioabsorbable or nonabsorbable, and may be a monofilament or a multifilament structure, but the braid structure of the bioabsorbable multifilament is particularly effective in the surgical suture. Bioabsorbable surgical sutures include, for example, conventional natural Gatgut, collagen or chitin, synthetic glycolide polymers, lactide polymers or copolymers of glycolide and lactide, glycolide and caprol The copolymer of lactone, polyhydroxybutyl acid and poly-p-dioxane include trimethylene carbonate polymer and the like.

In these polymers, a glycolide polymer, a lactide-like polymer, or a glycolide and lactide copolymer is preferable for the effect of improving the sliding property and the knot safety by coating. Coating to the suture may be performed by TBH alone. For example, the suture may be dried in powder form, or may be dissolved in a general volatile organic solvent, and the suture is immersed in the solution, followed by coating by evaporating off the solvent.

Since the coating agent used in the present invention has good adhesion to the surface of the surgical suture, and can be coated on the suture well by itself, it is possible to sufficiently improve the slipper of the suture even in a small amount. In addition, the coating agent used in the present invention may be coated on the suture in the form of a composition mixed with other materials. At this time, as other materials to be mixed in TBH, a biocompatible and thermoplastic or solvent-soluble polymer is preferable. When the soluble polymer is used in particular, the coating workability of the suture is good and can be uniformly coated.

When the surgical suture is a bioabsorbable polymer, the mixture with TBH is preferably a bioabsorbable polymer. For example, glycolide polymer, lactide polymer, copolymer of glycolide and lactide, polycaprolactone, polyoxyalkylene, polytetrafluoroethylene, silicone resin, etc. are mentioned. Among them, a glycolide polymer, a lactide polymer, a copolymer of glycolide and lactide, which is a bioabsorbable polymer, is particularly preferable.

When TBH is coated on a surgical suture as a composition mixed with the polymer, for example, when the polymer is a glycolide-lactide copolymer or polycaprolactone, the polymer is heated and melted at 200 ° C. or lower to add TBH. And it can be coated by passing a surgical suture through the melt. After coating, it is cooled by water or air cooling. The composition of the composition in this case is preferably 20% by weight or more, and more preferably 50% by weight or more of the TBH content in the total composition. If the content of TBH is within 20% by weight, the adhesion to the suture surface becomes weak, which is not preferable.

Moreover, the said polymer is made into room temperature-50 degreeC, and it melt | dissolves in a chloroform, dioxane, methylene chloride, and tetrahydrofuran solvent, and then, TBH is dissolved. The solution can be coated by dipping a surgical suture. The temperature at the time of coating is preferably room temperature ~ 50 ℃, the time to put the suture after the solution is 5 seconds to 2 minutes, can be sufficiently coated, after the coating is completed in the temperature range of room temperature ~ 120 ℃ about 1 ~ 24 Drying is performed in time to remove the organic solvent. At this time, drying under reduced pressure is more advantageous.

Surgical suture coated with a composition consisting of a mixture of TBH and the polymer, the polymer acts as a support between the suture and TBH to increase adhesion. Particularly in multifilament sutures, the coating helps to adhere well between the braided structures, thereby improving the knot sliding properties of the braided sutures, and in particular, the inconvenience of use, which is too elastic and soft.

When the composition of TBH and the polymer is coated on a suture, the amount of TBH in the composition is preferably at least about 20% by weight (composition ratio 1: 4). Especially preferably, it is 50 weight% or more, More preferably, it is 80 weight% or more. If it is less than 20% by weight, a good coating effect, i.e., good knot slipperiness cannot be expected, and it is difficult to slip the knot especially when wet.

In the suture coating according to the present invention, other coating agents or lubricants known in the art such as calcium stearate may be used together with the TBH. Also in this case, the amount of TBH in the coating composition is preferably 20% by weight or more.

In the suture of the present invention, the amount of TBH coated alone or as part of the composition may vary depending on the structure of the filament, for example, the number of filaments or the braid density, but preferably 0.1 to 20% by weight relative to the suture weight. Is appropriately selected. If it is less than 0.1% by weight, the slipperiness is difficult, so it is difficult to expect a good coating effect, and if it exceeds 20% by weight, it is coated like a chicken wax, and the appearance is rough. However, it is not preferable because of the low economic efficiency. More preferably, it is 0.5-10.0 weight%.

Next, examples of the present invention will be displayed and described in detail. In addition, the physical property value in an Example was measured with the following method.

(1) subjective method

During surgery, Tera's proposed suture knot method was tied around the cylindrical rod and slipped. This is a very simple and convenient way to assess slipperiness after knots. In order to know the knot slidability in the wet state, the sutures used at this time were evaluated after immersion in a water bath at 25 ° C. containing distilled water for 1 minute.

(2) objective method

F-meter (Model: R-1182, Rothschild, Switzerland) filament friction coefficient measuring device was used to quantitatively measure the friction between the suture and the ceramic.

(Examples 1 to 10) (Comparative Examples 1 to 3)

The powder of the various coating agents shown in the 1st table was coated by the dry coating method. In particular, the suture that passed through the powder-filled tube was dried at around 100 ° C. to obtain a coated suture. According to the difference with the suture weight before coating, the coating amount of the coating agent was also calculated as a percentage of the weight of the filament. After coating, slip characteristics were evaluated by subjective method and objective method. Here TBH was obtained in powder form in a freeze mill.

(Examples 11-19) (Comparative Examples 4-9)

As shown in Table 2, after dissolving various resins in the methylene chloride organic solvent, TBH having a number average molecular weight of 13,000 was added at various ratios to prepare a coating solution mixture. After immersing the suture in this solution for about 10 seconds, the solvent was removed by passing through a drying tube to obtain a coated suture. The weight of the obtained suture was measured and the amount of coating applied was calculated as a percentage of the suture weight, depending on the difference with the suture weight before coating.

The results are shown in Table 2.

(Examples 20-21)

After adding TBH to methylene chloride and dissolving, the suture was immersed for 10 seconds and then passed through a drying tube to remove the solvent. The weight of the obtained suture was measured and the amount of coating applied was calculated as a percentage of the suture weight, depending on the difference with the suture weight before coating. The results are shown in Table 3.

Table 1

(Note) The abbreviation of Suture material column is as follows.

PGA: Polyglycolide Multifilament Suture

PLA: Polylactide Multifilament Suture

PGLA: Glycolide-Lactide Copolymer Sutures

Table 2

Table 3

(Note) The symbol of the coating agent mixed component is as follows.

PGA: Polyglycolide

PLA: Polylactide

PCL: Polycaprolactone

PGLA: Glycolide-Lactide Copolymer

Knot Slip Evaluation Criteria

◎: Very good

○: Good

△: Normal

×: Impossible

Claims (10)

A surgical suture coating comprising a thermoplastic biodegradable hydrogel (TBH) alone in a surgical suture or a coating composition containing 20% by weight or more of TBH of up to 80% by weight of a suture coating lubricant. The surgical suture of claim 1, wherein the surgical suture is polyglycolic acid, polylactic acid, glycolide / lactide copolymer, glycolide / caprolactone copolymer, polyhydroxybutyl acid, poly-p-dioxane, trimethylene Surgical suture coating, characterized in that the bioabsorbable polymer, such as carbonate copolymer. The method of claim 1, wherein the thermoplastic biodegradable hydrogel (TBH) is synthesized by combining a hydrophilic non-degradable polymer (A) and a hydrophobic biodegradable polymer (B) represented by the following formula (I) a to (I) f Surgical suture coating, characterized in that the block biodegradable hydrogel polymer. Wherein A (-) is a hydrophilic non-degradable polymer such as polyethylene oxide (PEO) or polyethylene oxide / polypropylene oxide copolymer, and (B ---) is polylactide (PLA), polyglycolide (PGA) ), Hydrophobic biodegradable polymers such as PLA / PGA copolymer, polycaprolactone (PCL), polyorthoesters, polyanhydrides, and X is a chemical that degrades in vivo, such as amide bonds, ester bonds, and carbonate bonds. Y is a chemical bond which connects A and B or B, such as an amide bond, an ester bond, a carbonate bond, by covalent bond, n is an integer of 0-10, q is an integer of 3-4. The multi-block copolymer according to claim 3, wherein TBH is a multiblock copolymer including polyethylene oxide (PEO), polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), and the like. ') Coating for surgical suture, characterized in that. [HO (CH ₂ ) _Z- (OCHR ₁ COOCHR ₂ CO) m] ℓ-YA-Y '-[(COCHR ₁ OC (= O) CHR | ₂ O) mO (CH ₂ ) _Z -H] ℓ (I ) [HO (CH ₂ ) _Z- (O (CH ₂ ) ₅ COm] ℓ-YA-Y '-[(CO (CH ₂ ) ₅ O) mO (CH ₂ ) _Z -H] ℓ (I') Wherein A is a multiblock composed of hydrophilic and hydrophobic polymers, wherein [(CH ₂ CH ₂ O) _n -X- (OCH ₂ CH ₂ ) _n ] _r ; X is -O (COCH ₂ O) _x -,-[COCH (CH ₃ ) O] _x- , Y is CH _y NHCO-, Y 'is -CONHCH _y- ; R ₁ and R ₂ are hydrogen or methyl; x is an integer from 1 to 10; z is an integer from 1 to 5; y is 0, 1, or 2; Wherein l has a value of 3, 2, 1, m is an integer from 1 to 100, and n is an integer from 20 to 500; k is an integer from 0 to 10; r is an integer from 0 to 10. 4. The surgical suture coating of claim 3, wherein the weight ratio of polyethylene oxide (PEO) in the TBH ranges from 5% to 95% of the total TBH weight. The surgical suture coating of claim 1, wherein the content of the thermoplastic biodegradable hydrogel (TBH) is at least 50% by weight based on the total weight of the coating. The surgical suture coating of claim 1, wherein the suture coating lubricant is a bioabsorbable polymer. 8. The surgical suture of claim 7, wherein the bioabsorbable polymer is a glycolide polymer, a lactide polymer, a glycolide / lactide copolymer, polycaprolactone, polyoxyalkylene, polytetrafluoroethylene, silicone resin. Coating agent. Surgical suture for surgical surgical suture characterized in that the coating of 0.1 to 20% by weight relative to the suture weight of the thermoplastic biodegradable hydrogel (TBH) alone or a coating composition containing 20% by weight or more of TBH. The surgical suture of claim 9, wherein the weight of the coating agent is 0.5 to 10.0% by weight based on the weight of the suture.