WO2016093377A1 - Suture thread prepared using compound containing phosphorylcholine-like group - Google Patents

Suture thread prepared using compound containing phosphorylcholine-like group Download PDF

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Publication number
WO2016093377A1
WO2016093377A1 PCT/KR2014/011998 KR2014011998W WO2016093377A1 WO 2016093377 A1 WO2016093377 A1 WO 2016093377A1 KR 2014011998 W KR2014011998 W KR 2014011998W WO 2016093377 A1 WO2016093377 A1 WO 2016093377A1
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group
suture
phosphorylcholine
containing compound
hydrogen atom
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PCT/KR2014/011998
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French (fr)
Korean (ko)
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문제헌
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주식회사 네이처인랩
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Priority to PCT/KR2014/011998 priority Critical patent/WO2016093377A1/en
Publication of WO2016093377A1 publication Critical patent/WO2016093377A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/04—Surgical instruments, devices or methods, e.g. tourniquets for suturing wounds; Holders or packages for needles or suture materials
    • 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
    • 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
    • A61L17/14—Post-treatment to improve physical properties

Definitions

  • the present invention relates to sutures prepared using phosphorylcholine like group containing compounds.
  • Medical Textiles refers to all fibrous materials and products that are used as core parts and materials of medical devices (medical supplies) and quasi-drugs and act directly or indirectly on all life activities of the human body. It refers to a product in which fiber structural materials are essential among medical devices and quasi-drugs used in medical activities such as medication or surgical operation (to prevent or treat diseases).
  • medical fibers are classified into three categories: 1 therapeutic fiber, 2 body functional fiber, and 3 health care and sanitary fiber, depending on the scope of action.
  • Medical fiber products for human therapy include dozens of items, including catheters, artificial blood vessels, blood component separation filters, hemodialysis filters, surgical meshes, wound dressings, and sutures.
  • Absorbent biocompatible polymers are widely used in the manufacture of medical supplies.
  • the polymers used in medical products, especially sutures, have the appropriate tensile strength and the appropriate absorption rate for the purpose.
  • biocompatibility is required.
  • the phosphorylcholine-like group-containing polymer is due to the phospholipid-like structure derived from the biological membrane, and is known to have excellent properties in biocompatibility, antifouling properties, moisturizing properties such as inactivation of blood components and nonadsorption of biomaterials.
  • research and development on the synthesis and use of phosphorylcholine like group-containing polymers for the purpose of developing bio-related materials utilizing these functions are being actively conducted.
  • Such phosphorylcholine like group-containing polymers include phosphorylcholine like group containing monomers, in particular 2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethylphosphate [2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethylphosphate, also referred to as 2-methacryloyloxyethylphosphocholine, hereinafter abbreviated as MPC], is a monomer that is structurally similar to phosphatidylcholine, a cell wall component. Choline analogs are known to confer good biocompatibility.
  • the present invention provides a suture comprising suture fibers, a phosphorylcholine like group-containing compound present in the fibers.
  • the phosphorylcholine like group-containing compound may be a compound of Formula 1 or a polymer thereof.
  • X represents a divalent organic residue
  • Z represents a hydrogen atom or R 5 -O-CO-, where R 5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or a hydroxide having 1 to 10 carbon atoms.
  • Y represents an alkyleneoxy group having 1 to 20 carbon atoms
  • R 1 represents a hydrogen atom or a hydrocarbon group of 1 to 5 carbon atoms
  • R 2 , R 3 and R 4 are the same or different.
  • a group a hydrogen atom, a C1-C6 hydrocarbon group, or a hydroxy hydrocarbon group is represented, m is an integer of 1-20, n is an integer of 2-5)
  • the phosphorylcholine like group-containing compound may be a copolymer of the compound of Formula 1 and an monomer having an unsaturated group.
  • the phosphorylcholine like group-containing compound may be included in an amount of 8 to 15 parts by weight based on 100 parts by weight of the fiber.
  • the present invention also provides a method of preparing a suture fiber with an aqueous solution of a phosphorylcholine like group-containing compound, immersing the suture fiber in a solution of the phosphorylcholine-like group-containing compound, and drying the immersed fiber. It provides a method of producing a suture comprising.
  • the concentration of the solution of the phosphorylcholine like group-containing compound may be in the range of 4 to 12% by weight, and the immersing may be to immerse the suture fibers once for 12 to 36 hours.
  • the suture of the present invention is particularly excellent in biocompatibility and antimicrobial properties because it contains not only excellent tensile strength and bioabsorbability but also phosphorylcholine-like groups.
  • Figure 1 is a photograph of the antimicrobial test results of sutures for each PMPC aqueous solution concentration according to an embodiment of the present invention
  • Figure 2 is a photograph showing the results obtained by culturing the suture prepared in Comparative Example in the same manner
  • Figure 3 is a photograph of the antimicrobial test results of sutures in accordance with the PMPC aqueous solution immersion conditions according to an embodiment of the present invention.
  • the present invention provides sutures prepared using phosphorylcholine like group-containing compounds. That is, the suture according to one embodiment comprises a suture fiber, a phosphoryl choline-like group-containing compound present in the fiber. According to one embodiment of the present invention, the method of allowing the phosphorylcholine-like group-containing compound to be present in the suture fiber can be largely divided into three types.
  • the present invention provides a suture polymer obtained by reacting a polymer or copolymer comprising a phosphorylcholine group with polydioxanone, which is a raw material of the suture fiber, and a suture yarn prepared using the suture polymer as a main material.
  • a suture polymer obtained by reacting a polymer or copolymer comprising a phosphorylcholine group with polydioxanone, which is a raw material of the suture fiber, and a suture yarn prepared using the suture polymer as a main material.
  • the suture can be prepared by mixing the raw material of the conventional suture fiber and the compound containing phosphoryl choline similar group.
  • the raw material of the conventional suture fiber and the phosphorylcholine like group-containing compound are melt mixed and spun to provide a suture in which the two materials are blended.
  • the suture may be provided by modifying the surface by preparing a suture fiber as described above and then treating the suture fiber by coating the surface with a phosphorylcholine-like group-containing compound.
  • a surface modified biocompatible suture is provided by incorporating the suture into a solution in which a phosphorylcholine like group-containing compound is dissolved to coat the surface.
  • the phosphorylcholine like group-containing compound may be included in an amount of 8 to 15 parts by weight based on 100 parts by weight of the fiber. If it is less than the above range, the effect is insignificant, and if it exceeds the above range, it may be a problem in the suture properties.
  • the phosphorylcholine-like group-containing compound is prepared by copolymerizing with a polymer having a phosphorylcholine group or a monomer having a hydroxy group, and then reacting with another raw material of a suture by a method such as a graft reaction. Can be obtained.
  • Other raw materials of the suture include glycolide, trimethylene carbonate, caprolactone, polymers of paradioxanone, copolymers thereof, and the like.
  • a paradioxanone polymer or the copolymer containing paradioxanone is mentioned.
  • the polymer having a phosphorylcholine group and a hydroxyl group can be obtained by reacting the suture's monomer raw material or polymer with the polymer.
  • a new copolymer can be obtained by ring-opening-polymerizing paradioxanone with the hydroxyl group of the polymer which has a phosphorylcholine group and a hydroxyl group.
  • Sn (Oct) 2 stannous octoate / lipase B novozyme 435) can be used, but not limited.
  • the polymer which has the said phosphorylcholine group, or the copolymer which has a phosphorylcholine group and a hydroxyl group, and its manufacturing method are demonstrated.
  • the polymer having a phosphorylcholine group or a copolymer having a phosphorylcholine group and a hydroxy group can be prepared by various methods. Any form in which the phosphorylcholine group is present in the polymer structure is included in the present invention.
  • the weight average molecular weight of this polymer is not particularly limited, but is preferably in the range of 10,000 to 2,000,000 from the viewpoint of suture use.
  • the copolymerization is not limited, but the content of the phosphorylcholine compound based on the total monomers is 90 to 10% by weight, the content of the monomer having a hydroxyl group and an unsaturated group is preferably 10 to 90% by weight. Within this range biocompatibility may be particularly good.
  • X represents a divalent organic residue
  • Z represents a hydrogen atom or R 5 -O-CO- (wherein R 5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or a hydroxy having 1 to 10 carbon atoms Alkyl group)
  • Y represents an alkyleneoxy group having 1 to 20 carbon atoms.
  • R ⁇ 1> represents a hydrogen atom or a C1-C5 hydrocarbon group
  • R ⁇ 2> , R ⁇ 3> and R ⁇ 4> represent the same or another group and represent a hydrogen atom, a C1-C6 hydrocarbon group, or a hydroxy hydrocarbon group.
  • m is an integer of 1-20
  • n is an integer of 2-5.
  • Formula (1) may be represented by the following Formula (2).
  • Z represents a hydrogen atom or R 5 -O-CO- (wherein R 5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or a hydroxyalkyl group having 1 to 10 carbon atoms), and Y represents C1-C20 alkyleneoxy group is shown.
  • R ⁇ 1> represents a hydrogen atom or a C1-C5 hydrocarbon group
  • R ⁇ 2> , R ⁇ 3> and R ⁇ 4> represent the same or another group and represent a hydrogen atom, a C1-C6 hydrocarbon group, or a hydroxy hydrocarbon group.
  • m is an integer of 1-20
  • n is an integer of 2-5.
  • Phosphorylcholine monomers according to the present invention are not particularly limited, but 2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethylphosphate [2- (methacryloyloxy) ethyl- in terms of absorbency and biocompatibility. 2 '-(trimethylammonio) ethylphosphate, also referred to as 2-methacryloyloxyethylphosphorylcholine, hereinafter abbreviated as MPC] is preferred, but not limited thereto.
  • the unsaturated group is not limited, but may be acryl, vinyl, allyl, cycloalkene, or the like. Preferably it may be an acrylic monomer.
  • Unsaturated monomers in which a hydroxy group is present include, but are not limited to, 2-hydroxy ethyl acrylate, 2-hydroxy ethyl methacrylate, 2-hydroxy propyl acrylate, 2-hydroxy propyl methacrylate, 2-hydroxy Hydroxy butyl acrylate, 2-hydroxy butyl methacrylate, and the like.
  • a radical polymerization initiator used for polymerizing a phosphorylcholine compound or copolymerizing a phosphorylcholine compound and a monomer having a hydroxyl group and an unsaturated group is, for example, azobisisobutyronitrile (AIBN), azobisdimethyl Azo initiators such as valenzonitrile, azo initiators, benzoyl peroxide, lauroyl peroxide, potassium persulfate, di (2-ethylhexyl) peroxydicarbonate [di ( 2ethylhexyl) peroxydicarbonate], di (sec-butyl) peroxydicarbonate] di (isopropyl) peroxydicarbonate] di (isopropyl) peroxydicarbonate] di (cyclohexyl) peroxydicarbonate peroxydicarbonate], di (cetyl) peroxydicarbonate, di (n-propyl) peroxydicarbonate There is
  • the polymerization initiators include Duzot's Vazo 52G, Vazo 64G, Vazo 67G, Vazo 88G, etc., and the selection of the initiator includes a half life time of each temperature of the initiator and a boiling point of the organic solvent. Choose in consideration of.
  • a solvent may be used in the polymerization reaction, and an appropriate solvent is selected according to the polymerization method. It can be prepared by various methods such as suspension polymerization using an organic solvent as a reaction medium, reverse phase emulsion polymerization, precipitation polymerization or solution polymerization using water as a reaction medium.
  • the solvent is not limited but may be used in a 1 to 30 times weight ratio to the total weight of the monomers.
  • Organic solvents include, for example, toluene, benzene, cyclohexane, ethyl acetate, n-hexane, ethanol, n-propanol, isopropanol, t-butyl alcohol, methyl ethyl ketone, and the like. At least one organic solvent is mixed and used in an appropriate amount. For example, it can be used as a mixed solvent mixed in a weight ratio of 1:99 to 99: 1.
  • an additional monomer may be further used and copolymerized, but is not limited.
  • an appropriate amount of a crosslinking agent may be further included as necessary, and is not limited.
  • crosslinking agent examples include ethylene glycol diacrylate, ethylene glycol dimethacrylate, propylene glycol diacrylate, and propylene glycol dimethacrylate.
  • a polymer having a phosphorylcholine group or a polymer having a phosphorylcholine group and a hydroxy group is prepared, and then reacted with a monomer (paradioxanone, etc.), which is an existing suture raw material, to obtain a new suture raw material copolymer.
  • the copolymer of the present invention is preferably used as a monofilament suture because it is used as a monofilament suture having a fast absorbency, so that the wound of the tissue is less and the infection rate is lower than that of a multifilament suture. Do.
  • the linear strength of the single yarn suture using the copolymer of the present invention is 45,000 psi or more, preferably 45,000 to 70,000 psi, and more preferably 49,000 to 53,000 psi.
  • the knot-pull strength of the suture of the present invention may be at least 25,000 psi, preferably 30,000 to 50,000 psi, and more preferably 30,000 to 33,000 psi.
  • the modulus of the suture of the present invention is 180,000 psi or less, preferably 30,000 to 180,000 psi.
  • the suture according to an embodiment of the present invention may be a suture manufactured through the following method. That is, a suture may be manufactured by melt-mixing and spinning a conventional suture raw material and a phosphorylcholine like group-containing compound.
  • the bar is completed through four steps, and the suture raw material such as polydioxanone is melted into a gel state and then mixed with a phosphorylcholine-like group-containing compound to be melt mixed and melted.
  • the stretching process to increase the tensile strength and elasticity, it is possible to produce a suture mixed with a polydioxanone and a phosphoryl choline-like group-containing compound.
  • the phosphorylcholine-like group-containing compound may be a phosphorylcholine-based compound such as MPC, a polymer of a phosphorylcholine-based compound such as MPC, or a copolymer copolymerized with an unsaturated group monomer having a hydroxy group. . Since the description thereof has been sufficiently described above, the description thereof will be omitted.
  • a reactor capable of reacting with a hydroxyl group for example, a dioxanone, a carbonyl group, etc.
  • a reactor capable of reacting with a hydroxyl group for example, a dioxanone, a carbonyl group, etc.
  • the suture according to an embodiment of the present invention may be a suture manufactured by coating and modifying the surface of the suture fiber. That is, the phosphorylcholine-like group-containing compound may be surface modified with a biocompatible suture by coating (surface) the surface of the suture fibers by impregnating (immersing) the fibers for suture in a solution dissolved in a solvent.
  • the phosphorylcholine-like group-containing compound may be a phosphorylcholine-based compound such as MPC described above, a polymer of phosphorylcholine-based compound such as MPC, or a copolymer copolymerized with an unsaturated group monomer having a hydroxy group.
  • a reactor capable of reacting with a hydroxyl group for example, a dioxanone, a carbonyl group, etc.
  • a reactor capable of reacting with a hydroxyl group is reacted with the suture, thereby reacting the two components more chemically.
  • a hydroxyl group for example, a dioxanone, a carbonyl group, etc.
  • the solvent used is not limited, and examples thereof include water, toluene, benzene, cyclohexane, ethyl acetate, n-hexane, ethanol, n-propanol, isopropanol, t-butyl alcohol, methyl ethyl ketone, and the like.
  • One may be used and one or more organic solvents may be mixed and used in an appropriate amount.
  • the concentration of the solution of the phosphorylcholine like group-containing compound is preferably in the range of 4 to 12% by weight. If the concentration range is less than the immersion effect is insignificant, if it exceeds the range may be a problem in the suture properties.
  • the immersion conditions are not limited, but immersion of the suture fibers in the solution containing phosphorylcholine like group once for 12 to 36 hours may be good as shown in the following examples.
  • concentration of poly 2-Methacryloyloxyethyl Phosphoryl Choline (PMPC) aqueous solution was prepared by immersing the PDO (polydioxanone) suture was tested for concentration optimization. At this time, the suture used was 1mm in diameter and immersed in a constant length of 5cm for one day and then warm air dried.
  • PMPC poly 2-Methacryloyloxyethyl Phosphoryl Choline
  • the microbial adhesion test was performed by observing colonies of Staphylococcus aureus attached to MPC coated sutures to test the antimicrobial activity of the immersed sutures obtained in Examples 1-4 and Comparative Examples. After incubating the Staphylococcus aureus ATCC6538 (S.
  • the coating uniformity of the suture coated by the optimized concentration and immersion method was photographed by scanning electron microscopy (SEM), it was confirmed that more than 90% uniform coating was made.
  • the suture according to the present invention is not only excellent in tensile strength and bioabsorption, but also contains phosphorylcholine-like groups, so that the suture is particularly excellent in biocompatibility and antibacterial properties, and thus it is industrially useful.

Abstract

The present invention provides: a polymer for a suture thread, obtained by reaction of a polymer, which has a phosphorylcholine group and a hydroxyl group, and polydioxanone, which is a suture thread raw material; and a suture thread prepared therefrom. In addition, the present invention provides a suture thread prepared by melt mixing a suture thread raw material and a compound containing a phosphorylcholine-like group, followed by spinning. In addition, the present invention provides a biocompatible suture thread that is surface-modified by surface coating with a compound containing a phosphorylcholine-like group.

Description

포스포릴콜린 유사기 함유 화합물을 이용하여 제조된 봉합사Suture made using a phosphorylcholine like group-containing compound
본 발명은 포스포릴콜린 유사기 함유 화합물을 이용하여 제조된 봉합사에 관한 것이다.The present invention relates to sutures prepared using phosphorylcholine like group containing compounds.
메디컬 섬유(Medical Textiles)란 의료기기(의료용품) 및 의약외품의 핵심 부품·소재로 사용되어 인체의 모든 생명활동에 직간접적으로 작용되는 모든 섬유상의 소재 및 제품을 말하는 것으로서, 진찰, 검안, 처방, 투약 또는 외과수술 등의 의료행위 (질병의 예방이나 치료행위를 말하는 것)에 사용되는 의료기기 및 의약외품 중, 섬유구조재료가 필수적으로 들어가는 제품을 말한다. 일반적으로 메디컬 섬유는 작용범위에 따라 ① 치료용 섬유, ② 신체기능보조용 섬유, ③ 헬스케어 및 위생섬유의 3개 제품군으로 분류되며, 이 중에서 치료용 섬유와 신체기능보조용 섬유가 인체(생체)치료용 섬유구조재료에 해당된다. 인체치료용 메디컬 섬유제품은 카테타, 인공혈관, 혈액 성분 분리 필터, 혈액 투석 필터, 수술용 메시, 창상피복재, 봉합사 등 수십 종의 아이템이 있다. Medical Textiles refers to all fibrous materials and products that are used as core parts and materials of medical devices (medical supplies) and quasi-drugs and act directly or indirectly on all life activities of the human body. It refers to a product in which fiber structural materials are essential among medical devices and quasi-drugs used in medical activities such as medication or surgical operation (to prevent or treat diseases). In general, medical fibers are classified into three categories: ① therapeutic fiber, ② body functional fiber, and ③ health care and sanitary fiber, depending on the scope of action. Corresponds to therapeutic fiber structural materials. Medical fiber products for human therapy include dozens of items, including catheters, artificial blood vessels, blood component separation filters, hemodialysis filters, surgical meshes, wound dressings, and sutures.
흡수성의 생체적합 고분자는 의료용품의 제조에 널리 사용되고 있다. 의료용품 특히 봉합사에 사용되어지는 고분자는 적절한 인장강도와 함께 용도에 맞는 적절한 흡수율을 가지고 있어 생체에 흡수되어야 한다. 이와 함께 생체 적합성이 요구된다.Absorbent biocompatible polymers are widely used in the manufacture of medical supplies. The polymers used in medical products, especially sutures, have the appropriate tensile strength and the appropriate absorption rate for the purpose. In addition, biocompatibility is required.
한편, 포스포릴콜린 유사기 함유 중합체는 생체막에 유래하는 인지질 유사구조에 기인하는 것으로서, 혈액성분 불활성화, 생체물질 비흡착성 등의 생체 적합성, 방오성, 보습성 등에 있어서 우수한 성질을 가지는 것이 알려져 있다. 그리고 이들의 기능을 살린 생체관련재료의 개발을 목적으로 한 포스포릴콜린 유사기 함유 중합체의 합성 및 그 용도에 관한 연구개발이 활발히 행하여지고 있다.On the other hand, the phosphorylcholine-like group-containing polymer is due to the phospholipid-like structure derived from the biological membrane, and is known to have excellent properties in biocompatibility, antifouling properties, moisturizing properties such as inactivation of blood components and nonadsorption of biomaterials. In addition, research and development on the synthesis and use of phosphorylcholine like group-containing polymers for the purpose of developing bio-related materials utilizing these functions are being actively conducted.
이러한 포스포릴콜린 유사기 함유 중합체에는 포스포릴콜린 유사기 함유 단량체가 포함되는데, 그 중 특히 2-(메타크릴로일옥시)에틸-2'-(트리메틸암모니오)에틸포스페이트[2-(methacryloyloxy)ethyl-2'-(trimethylammonio)ethylphosphate, 2-메타클리로일옥시에틸포스폴린콜린이라고도 함, 이하, MPC로 약칭함]라는 단량체는, 세포벽 구성 성분인 포스파티딜콜린(Phosphatidyl choline)과 구조적으로 유사한 포스포릴콜린 유사기가 존재하여 우수한 생체 적합성을 부여하는 것으로 알려져 있다.Such phosphorylcholine like group-containing polymers include phosphorylcholine like group containing monomers, in particular 2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethylphosphate [2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethylphosphate, also referred to as 2-methacryloyloxyethylphosphocholine, hereinafter abbreviated as MPC], is a monomer that is structurally similar to phosphatidylcholine, a cell wall component. Choline analogs are known to confer good biocompatibility.
본 발명은 적절한 인장강도, 생체 흡수성과 함께 생체 적합성, 항균성이 우수한 봉합사를 제공하는 것을 목적으로 한다.It is an object of the present invention to provide a suture excellent in biocompatibility and antimicrobial properties with appropriate tensile strength and bioabsorbability.
상기의 과제를 해결하기 위한 수단으로서, As a means for solving the above problems,
본 발명은 봉합사용 섬유, 상기 섬유에 존재하는 포스포릴콜린 유사기 함유 화합물을 포함하여 이루어진 봉합사를 제공한다.The present invention provides a suture comprising suture fibers, a phosphorylcholine like group-containing compound present in the fibers.
상기 포스포릴콜린 유사기 함유 화합물은 하기 화학식 1의 화합물 또는 그 중합체일 수 있다.The phosphorylcholine like group-containing compound may be a compound of Formula 1 or a polymer thereof.
[화학식 (1)][Formula (1)]
Figure PCTKR2014011998-appb-I000001
Figure PCTKR2014011998-appb-I000001
(상기 화학식 (1)에서 X는 2가의 유기잔기를 나타내고, Z는 수소원자 또는 R5-O-CO-(여기서, R5는 수소원자, 탄소수 1~10의 알킬기 또는 탄소수 1~10의 히드록시알킬기를 나타낸다)를 나타내고, Y는 탄소수 1~20의 알킬렌옥시기를 나타낸다. 또한, R1은 수소원자 또는 탄소수 1~5의 탄화수소기를 나타내고, R2, R3 및 R4는 동일 또는 다른 기로서, 수소원자, 탄소수 1~6의 탄화수소기 또는 히드록시 탄화수소기를 나타낸다. 또한, m은 1~20의 정수이고, n은 2~5의 정수이다)(In Formula (1), X represents a divalent organic residue, Z represents a hydrogen atom or R 5 -O-CO-, where R 5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or a hydroxide having 1 to 10 carbon atoms. Oxyalkyl group), Y represents an alkyleneoxy group having 1 to 20 carbon atoms, R 1 represents a hydrogen atom or a hydrocarbon group of 1 to 5 carbon atoms, and R 2 , R 3 and R 4 are the same or different. As a group, a hydrogen atom, a C1-C6 hydrocarbon group, or a hydroxy hydrocarbon group is represented, m is an integer of 1-20, n is an integer of 2-5)
또한, 상기 포스포릴콜린 유사기 함유 화합물은 상기 화학식 1의 화합물과 불포화기 존재 단량체의 공중합체일 수 있다. 또한, 상기 포스포릴콜린 유사기 함유 화합물은 상기 섬유 100 중량 대비 8 내지 15 중량부 포함될 수 있다.In addition, the phosphorylcholine like group-containing compound may be a copolymer of the compound of Formula 1 and an monomer having an unsaturated group. In addition, the phosphorylcholine like group-containing compound may be included in an amount of 8 to 15 parts by weight based on 100 parts by weight of the fiber.
본 발명은 또한, 포스포릴콜린 유사기 함유 화합물의 수용액과 봉합사용 섬유를 준비하는 단계, 상기 포스포릴콜린 유사기 함유 화합물의 용액에 봉합사용 섬유를 침지하는 단계 및 침지된 섬유를 건조하는 단계를 포함하여 이루어진 봉합사의 제조방법을 제공한다. 상기 포스포릴콜린 유사기 함유 화합물의 용액의 농도는 4 내지 12 중량% 범위내일 수 있으며, 상기 침지하는 단계는 봉합사용 섬유를 12 내지 36시간 동안 1회 침지하는 것일 수 있다.The present invention also provides a method of preparing a suture fiber with an aqueous solution of a phosphorylcholine like group-containing compound, immersing the suture fiber in a solution of the phosphorylcholine-like group-containing compound, and drying the immersed fiber. It provides a method of producing a suture comprising. The concentration of the solution of the phosphorylcholine like group-containing compound may be in the range of 4 to 12% by weight, and the immersing may be to immerse the suture fibers once for 12 to 36 hours.
본 발명의 봉합사는 인장강도, 생체 흡수성이 우수할 뿐만 아니라 포스포릴콜린 유사기를 함유함으로써 생체 적합성, 항균성이 특히 우수하다.The suture of the present invention is particularly excellent in biocompatibility and antimicrobial properties because it contains not only excellent tensile strength and bioabsorbability but also phosphorylcholine-like groups.
도 1은 본 발명의 일실시예에 따른 PMPC 수용액 농도별 봉합사의 항균 테스트 결과 사진이며,Figure 1 is a photograph of the antimicrobial test results of sutures for each PMPC aqueous solution concentration according to an embodiment of the present invention,
도 2는 비교예에 의해 제조된 봉합사를 동일한 방식으로 배양하여 나타난 결과를 나타낸 사진이며,Figure 2 is a photograph showing the results obtained by culturing the suture prepared in Comparative Example in the same manner,
도 3은 본 발명의 일실시예에 따른 PMPC 수용액 침지 조건에 따른 봉합사의 항균 테스트 결과 사진이다.Figure 3 is a photograph of the antimicrobial test results of sutures in accordance with the PMPC aqueous solution immersion conditions according to an embodiment of the present invention.
이하, 본 발명을 구체적으로 설명한다. 다만, 하기 실시예는 본 발명을 보다 명확히 예시하기 위한 것일 뿐이므로, 비록 한정적, 단정적 표현이 존재하여도 본 발명의 보호범위를 한정하는 것은 아니다.Hereinafter, the present invention will be described in detail. However, the following examples are only intended to more clearly illustrate the present invention, but the present invention does not limit the protection scope of the present invention even though there is limited or assertive expression.
본 발명은 포스포릴콜린 유사기 함유 화합물을 이용하여 제조된 봉합사를 제공한다. 즉, 일실시예에 따른 봉합사는 봉합사용 섬유, 상기 섬유에 존재하는 포스포릴콜린 유사기 함유 화합물을 포함하여 이루어진다. 본 발명의 일실시예에 따라, 포스포릴콜린 유사기 함유 화합물을 봉합사용 섬유에 존재하게 하는 방법은 크게 3가지로 나누어질 수 있다. The present invention provides sutures prepared using phosphorylcholine like group-containing compounds. That is, the suture according to one embodiment comprises a suture fiber, a phosphoryl choline-like group-containing compound present in the fiber. According to one embodiment of the present invention, the method of allowing the phosphorylcholine-like group-containing compound to be present in the suture fiber can be largely divided into three types.
첫째, 포스포릴콜린 유사기 함유 화합물이 봉합사의 주재료로 사용되는 경우를 들 수 있다. 일례로서, 본 발명은 포스포릴콜린 그룹을 포함하는 중합체 또는 공중합체와 봉합사용 섬유의 원료인 폴리디옥사논 등과의 반응으로 얻어지는 봉합사용 중합체를 제공하며, 상기 봉합사용 중합체를 주재료로서 제조된 봉합사를 제공할 수 있다.First, the case where a phosphorylcholine like group containing compound is used as a main material of a suture is mentioned. As an example, the present invention provides a suture polymer obtained by reacting a polymer or copolymer comprising a phosphorylcholine group with polydioxanone, which is a raw material of the suture fiber, and a suture yarn prepared using the suture polymer as a main material. Can be provided.
둘째, 기존 봉합사용 섬유의 원료와 포스포릴콜린 유사기 함유 화합물을 혼합하여 봉합사를 제조할 수 있다. 일례로서, 기존의 봉합사용 섬유의 원료와 포스포릴콜린 유사기 함유 화합물을 용융 혼합한 뒤 방사하여 두 재료가 블랜딩된 봉합사를 제공한다.Second, the suture can be prepared by mixing the raw material of the conventional suture fiber and the compound containing phosphoryl choline similar group. As an example, the raw material of the conventional suture fiber and the phosphorylcholine like group-containing compound are melt mixed and spun to provide a suture in which the two materials are blended.
셋째, 기존처럼 봉합사용 섬유를 제조한 뒤, 포스포릴콜린 유사기 함유 화합물로 표면을 코팅하는 등의 방식으로 처리함으로써 표면을 개질하여 봉합사를 제공할 수 있다. 일례로서, 포스포릴콜린 유사기 함유 화합물이 용해된 용액에 봉합사를 합침하여 표면을 코팅함으로써 표면 개질된 생체 적합성 봉합사를 제공한다. Third, the suture may be provided by modifying the surface by preparing a suture fiber as described above and then treating the suture fiber by coating the surface with a phosphorylcholine-like group-containing compound. As an example, a surface modified biocompatible suture is provided by incorporating the suture into a solution in which a phosphorylcholine like group-containing compound is dissolved to coat the surface.
한편, 제한되지 않으나 상기 포스포릴콜린 유사기 함유 화합물은 섬유 100 중량 대비 8 내지 15 중량부 포함되는 것이 좋다. 상기 범위 미만에서는 효과가 미미하고, 상기 범위를 초과하는 경우에는 봉합사 물성에 문제될 수 있다.On the other hand, it is not limited, but the phosphorylcholine like group-containing compound may be included in an amount of 8 to 15 parts by weight based on 100 parts by weight of the fiber. If it is less than the above range, the effect is insignificant, and if it exceeds the above range, it may be a problem in the suture properties.
먼저, 포스포릴콜린 유사기 함유 화합물이 봉합사의 주재료로 사용되는 경우를 설명한다. 일례로서, 상기 포스포릴콜린 유사기 함유 화합물은 포스포릴콜린계 그룹을 갖는 중합체, 또는 히드록시기를 갖는 단량체와 함께 공중합하여 얻어지는 공중합체를 제조한 뒤, 봉합사의 다른 원료와 그래프트 반응 등의 방법으로 반응시켜 얻어질 수 있다. 상기 봉합사의 다른 원료로는 글리콜라이드, 트리메틸렌카보네이트, 카프로락톤, 파라디옥사논의 중합물 및 이들의 공중합물 등을 들 수 있다. 바람직하기로는 파라디옥사논 중합물 또는 파라디옥사논이 포함된 공중합물을 들 수 있다. 포스포릴콜린계 그룹 및 히드록시기를 갖는 중합체는 상기 봉합사의 단량체 원료 또는 중합물과 반응시킴으로써 봉합사의 주재료를 얻을 수 있다. 일례로서, 포스포릴콜린계 그룹 및 히드록시기를 갖는 중합체의 히드록시기로 파라디옥사논을 개환 중합 반응시킴으로써 새로운 공중합물을 얻을 수 있다. 이 개환 중합 반응을 위해, 제한되지 않으나 Sn(Oct)2stannous octoate/ Lipase B(novozyme 435)를 사용할 수 있다.First, the case where a phosphorylcholine like group containing compound is used as a main material of suture is demonstrated. As an example, the phosphorylcholine-like group-containing compound is prepared by copolymerizing with a polymer having a phosphorylcholine group or a monomer having a hydroxy group, and then reacting with another raw material of a suture by a method such as a graft reaction. Can be obtained. Other raw materials of the suture include glycolide, trimethylene carbonate, caprolactone, polymers of paradioxanone, copolymers thereof, and the like. Preferably, a paradioxanone polymer or the copolymer containing paradioxanone is mentioned. The polymer having a phosphorylcholine group and a hydroxyl group can be obtained by reacting the suture's monomer raw material or polymer with the polymer. As an example, a new copolymer can be obtained by ring-opening-polymerizing paradioxanone with the hydroxyl group of the polymer which has a phosphorylcholine group and a hydroxyl group. For this ring-opening polymerization reaction, Sn (Oct) 2 stannous octoate / lipase B (novozyme 435) can be used, but not limited.
상기 포스포릴콜린계 그룹을 갖는 중합체, 또는 포스포릴콜린계 그룹 및 히드록시기를 갖는 공중합체 및 그 제조방법을 설명한다.The polymer which has the said phosphorylcholine group, or the copolymer which has a phosphorylcholine group and a hydroxyl group, and its manufacturing method are demonstrated.
상기 포스포릴콜린계 그룹을 갖는 중합체, 또는 포스포릴콜린계 그룹 및 히드록시기를 갖는 공중합체는 다양한 방법으로 제조될 수 있다. 그 중합체 구조에 있어서 포스포릴콜린기가 존재하는 형태라면 본 발명에 포함된다. 이 중합체의 중량 평균 분자량은 크게 한정되지 않으나, 봉합사용 관점에서 10,000~2,000,000 범위내인 것이 바람직하다. The polymer having a phosphorylcholine group or a copolymer having a phosphorylcholine group and a hydroxy group can be prepared by various methods. Any form in which the phosphorylcholine group is present in the polymer structure is included in the present invention. The weight average molecular weight of this polymer is not particularly limited, but is preferably in the range of 10,000 to 2,000,000 from the viewpoint of suture use.
일례로는 하기 화학식 (1)의 포스포릴콜린계 화합물을 중합하여, 또는 하기 화학식 (1)의 포스포릴콜린계 화합물 및 히드록시기와 불포화기를 갖는 단량체를 공중합하여 얻어질 수 있다. 공중합시, 제한되지 않으나 전체 단량체 기준 포스포릴콜린계 화합물의 함량은 90 ~ 10 중량%, 히드록시기와 불포화기를 갖는 단량체의 함량은 10 ~ 90 중량%인 것이 좋다. 상기 범위내에서 생체 적합성이 특히 우수할 수 있다.For example, it can be obtained by polymerizing a phosphorylcholine compound of the formula (1) or copolymerizing a phosphorylcholine compound of the formula (1) and a monomer having a hydroxyl group and an unsaturated group. The copolymerization is not limited, but the content of the phosphorylcholine compound based on the total monomers is 90 to 10% by weight, the content of the monomer having a hydroxyl group and an unsaturated group is preferably 10 to 90% by weight. Within this range biocompatibility may be particularly good.
[화학식 (1)][Formula (1)]
Figure PCTKR2014011998-appb-I000002
Figure PCTKR2014011998-appb-I000002
상기 화학식 (1)에서 X는 2가의 유기잔기를 나타내고, Z는 수소원자 또는 R5-O-CO-(여기서, R5는 수소원자, 탄소수 1~10의 알킬기 또는 탄소수 1~10의 히드록시알킬기를 나타낸다)를 나타내고, Y는 탄소수 1~20의 알킬렌옥시기를 나타낸다. 또한, R1은 수소원자 또는 탄소수 1~5의 탄화수소기를 나타내고, R2, R3 및 R4는 동일 또는 다른 기로서, 수소원자, 탄소수 1~6의 탄화수소기 또는 히드록시 탄화수소기를 나타낸다. 또한, m은 1~20의 정수이고, n은 2~5의 정수이다.In Formula (1), X represents a divalent organic residue, Z represents a hydrogen atom or R 5 -O-CO- (wherein R 5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or a hydroxy having 1 to 10 carbon atoms Alkyl group), and Y represents an alkyleneoxy group having 1 to 20 carbon atoms. In addition, R <1> represents a hydrogen atom or a C1-C5 hydrocarbon group, and R <2> , R <3> and R <4> represent the same or another group and represent a hydrogen atom, a C1-C6 hydrocarbon group, or a hydroxy hydrocarbon group. In addition, m is an integer of 1-20, n is an integer of 2-5.
상기 화학식 (1)은 보다 구체적으로는, 하기 화학식 (2)로 표현될 수 있다.More specifically, Formula (1) may be represented by the following Formula (2).
[화학식 (2)][Formula (2)]
상기 화학식 (2)에서 Z는 수소원자 또는 R5-O-CO-(여기서, R5는 수소원자, 탄소수 1~10의 알킬기 또는 탄소수 1~10의 히드록시알킬기를 나타낸다)를 나타내고, Y는 탄소수 1~20의 알킬렌옥시기를 나타낸다. 또한, R1은 수소원자 또는 탄소수 1~5의 탄화수소기를 나타내고, R2, R3 및 R4는 동일 또는 다른 기로서, 수소원자, 탄소수 1~6의 탄화수소기 또는 히드록시 탄화수소기를 나타낸다. 또한, m은 1~20의 정수이고, n은 2~5의 정수이다.In Formula (2), Z represents a hydrogen atom or R 5 -O-CO- (wherein R 5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or a hydroxyalkyl group having 1 to 10 carbon atoms), and Y represents C1-C20 alkyleneoxy group is shown. In addition, R <1> represents a hydrogen atom or a C1-C5 hydrocarbon group, and R <2> , R <3> and R <4> represent the same or another group and represent a hydrogen atom, a C1-C6 hydrocarbon group, or a hydroxy hydrocarbon group. In addition, m is an integer of 1-20, n is an integer of 2-5.
상기 포스포릴콜린계 화합물의 구체적인 일례로는, 2-((메타)아크릴로일옥시)에틸-2'-(트리메틸암모니오)에틸포스페이트, 3-((메타)아크릴로일옥시)프로필-2'-(트리메틸암모니오)에틸포스페이트, 4-((메타)아크릴로일옥시)부틸-2'-(트리메틸암모니오)에틸포스페이트, 5-((메타)아크릴로일옥시)펜틸-2'-(트리메틸암모니오)에틸포스페이트, 6((메타)아크릴로일옥시)헥실-2'-(트리메틸암모니오)에틸포스페이트, 2-((메타)아크릴로일옥시)에틸-2'-(트리에틸암모니오)에틸포스페이트, 2-((메타)아크릴로일옥시)에틸-2'-(트리프로필암모니오)에틸포스페이트, 2-((메타)아크릴로일옥시)에틸-2'(트리부틸암모니오)에틸포스페이트, 2-((메타)아크릴로일옥시)프로필-2'-(트리메틸암모니오)에틸포스페이트, 2-((메타)아크릴로일옥시)부틸-2'-(트리메틸암모니오)에틸포스페이트, 2-((메타)아크릴로일옥시)펜틸-2'-(트리메틸암모니오)에틸포스페이트, 2-((메타)아크릴로일옥시)헥실-2'-(트리메틸암모니오)에틸포스페이트, 2-(비닐옥시)에틸-2'-(트리메틸암모니오)에틸포스페이트, 2-(알릴록시)에틸-2'-(트리메틸암모니오)에틸포스페이트, 2-(p-비닐벤질옥시)에틸-2'-(트리메틸암모니오)에틸포스페이트, 2-(p-비닐벤조일옥시)에틸-2'-(트리메틸암모니오)에틸포스페이트, 2-(스티릴옥시)에틸-2'-(트리메틸암모니오)에틸포스페이트, 2-(p-비닐벤질)에틸-2'-(트리메틸암모니오)에틸포스페이트, 2-(비닐옥시카르보닐)에틸-2'-(트리메틸암모니오)에틸포스페이트, 2-(알릴옥시카르보닐)에틸-2'-(트리메틸암모니오)에틸포스페이트, 2-(아크릴로일아미노)에틸-2'-(트리메틸암모니오)에틸포스페이트, 2-(비닐카르보닐아미노)에틸-2'-(트리메틸암모니오)에틸포스페이트, 2-(알릴옥시카르보닐아미노)에틸-2'-(트리메틸암모니오)에틸포스페이트, 2-(부테로일옥시)에틸-2'-(트리메틸암모니오)에틸포스페이트, 2-(크로토노일옥시)에틸-2'-(트리메틸암모니오)에틸포스페이트, 에틸(2'-트리메틸암모니오 에틸포스포릴에틸)프말레이트, 부틸-(2'-트리메틸암모니오 에틸포스포릴에틸)프말레이트, 히드록시에틸-(2'-트리메틸암모니오 에틸포스포릴에틸)프말레이트, 에틸-(2'-트리메틸암모니오 에틸포스포릴에틸)프말레이트, 부틸(2'-트리메틸암모니오 에틸포스포릴에틸)프말레이트, 히드록시에틸-(2'-트리메틸암모니오 에틸포스포릴에틸)프말레이트에서 1종 이상 선택하여 사용할 수 있다. 한편, 본 명세서에서, “(메타)아크릴”이라는 용어는 “아크릴” 또는 “메타크릴” 등을 모두 의미한다. As a specific example of the said phosphorylcholine type compound, 2-((meth) acryloyloxy) ethyl-2 '-(trimethylammonio) ethyl phosphate and 3-((meth) acryloyloxy) propyl-2 '-(Trimethylammonio) ethylphosphate, 4-((meth) acryloyloxy) butyl-2'-(trimethylammonio) ethylphosphate, 5-((meth) acryloyloxy) pentyl-2'- (Trimethylammonio) ethyl phosphate, 6 ((meth) acryloyloxy) hexyl-2 '-(trimethylammonio) ethyl phosphate, 2-((meth) acryloyloxy) ethyl-2'-(triethyl Ammonio) ethyl phosphate, 2-((meth) acryloyloxy) ethyl-2 '-(tripropylammonio) ethyl phosphate, 2-((meth) acryloyloxy) ethyl-2' (tributylammonium) 5) ethylphosphate, 2-((meth) acryloyloxy) propyl-2 '-(trimethylammonio) ethylphosphate, 2-((meth) acryloyloxy) butyl-2'-(trimethylammonio) Ethylphosphate, 2-(( Meta) acryloyloxy) pentyl-2 '-(trimethylammonio) ethylphosphate, 2-((meth) acryloyloxy) hexyl-2'-(trimethylammonio) ethylphosphate, 2- (vinyloxy) Ethyl-2 '-(trimethylammonio) ethylphosphate, 2- (allyloxy) ethyl-2'-(trimethylammonio) ethylphosphate, 2- (p-vinylbenzyloxy) ethyl-2 '-(trimethylammonio ) Ethylphosphate, 2- (p-vinylbenzoyloxy) ethyl-2 '-(trimethylammonio) ethylphosphate, 2- (styryloxy) ethyl-2'-(trimethylammonio) ethylphosphate, 2- (p -Vinylbenzyl) ethyl-2 '-(trimethylammonio) ethylphosphate, 2- (vinyloxycarbonyl) ethyl-2'-(trimethylammonio) ethylphosphate, 2- (allyloxycarbonyl) ethyl-2 ' -(Trimethylammonio) ethyl phosphate, 2- (acryloylamino) ethyl-2 '-(trimethylammonio) ethyl phosphate, 2- (vinylcarbonylamino) ethyl-2'-(trimethylammonio) ethylphosphate pay , 2- (allyloxycarbonylamino) ethyl-2 '-(trimethylammonio) ethylphosphate, 2- (buteroyloxy) ethyl-2'-(trimethylammonio) ethylphosphate, 2- (crotono Yloxy) ethyl-2 '-(trimethylammonio) ethylphosphate, ethyl (2'-trimethylammonio ethylphosphorylethyl) phmaleate, butyl- (2'-trimethylammonio ethylphosphorylethyl) phmaleate, hydrate Oxyethyl- (2'-trimethylammonio ethylphosphorylethyl) phmaleate, ethyl- (2'-trimethylammonio ethylphosphorylethyl) phmaleate, butyl (2'-trimethylammonio ethylphosphorylethyl) phmaleate And hydroxyethyl- (2'-trimethylammonio ethylphosphorylethyl) fmaleate can be used by selecting one or more. On the other hand, in the present specification, the term "(meth) acryl" means both "acryl" or "methacryl".
본 발명에 따른 포스포릴콜린계 단량체는 크게 제한되지 않으나, 흡수성 및 생체 적합성 면에서 2-(메타크릴로일옥시)에틸-2'-(트리메틸암모니오)에틸포스페이트[2-(methacryloyloxy)ethyl-2'-(trimethylammonio)ethylphosphate, 2-메타클리로일옥시에틸포스폴린콜린(2-methacryloyloxyethylphosphorylcholine)이라고도 함, 이하, MPC로 약칭함]가 바람직하지만 이에 한정되는 것은 아니다.Phosphorylcholine monomers according to the present invention are not particularly limited, but 2- (methacryloyloxy) ethyl-2 '-(trimethylammonio) ethylphosphate [2- (methacryloyloxy) ethyl- in terms of absorbency and biocompatibility. 2 '-(trimethylammonio) ethylphosphate, also referred to as 2-methacryloyloxyethylphosphorylcholine, hereinafter abbreviated as MPC] is preferred, but not limited thereto.
상기 히드록시기와 불포화기를 갖는 단량체에서, 불포화기로는 제한되지 않으나, 아크릴(acryl), 비닐(vinyl), 알릴(allyl), 사이클로알켄(cycloalkene) 등일 수 있다. 바람직하기로는 아크릴계 단량체일 수 있다.In the monomer having a hydroxyl group and an unsaturated group, the unsaturated group is not limited, but may be acryl, vinyl, allyl, cycloalkene, or the like. Preferably it may be an acrylic monomer.
히드록시기가 존재하는 불포화기 단량체로는, 제한되지 않으나 2-히드록시 에틸 아크릴레이트, 2-히드록시 에틸 메타크릴레이트, 2-히드록시 프로필 아크릴레이트, 2-히드록시 프로필 메타크릴레이트, 2-히드록시 부틸 아크릴레이트, 2-히드록시 부틸 메타크릴레이트 등을 들 수 있다.Unsaturated monomers in which a hydroxy group is present include, but are not limited to, 2-hydroxy ethyl acrylate, 2-hydroxy ethyl methacrylate, 2-hydroxy propyl acrylate, 2-hydroxy propyl methacrylate, 2-hydroxy Hydroxy butyl acrylate, 2-hydroxy butyl methacrylate, and the like.
포스포릴콜린계 화합물을 중합하거나, 포스포릴콜린계 화합물 및 히드록시기와 불포화기를 갖는 단량체를 공중합하기 위하여 사용되는 라디칼 중합개시제는, 예를 들면 아조비스이소부틸로니트릴(Azobisisobutyronitrile, AIBN), 아조비스디메틸발레로니트릴(Azobisdimethylvaleronitrile) 등과 같은 아조 개시제, 벤조일퍼옥사이드(Benzoyl peroxide), 라우로일퍼옥사이드(Lauroyl peroxide), 포타지움퍼설페이트(Potassium persulfate), 디(2-에틸헥실)퍼옥시디카보네이트[di(2ethylhexyl)peroxydicarbonate], 디(sec-부틸)퍼옥시디카보네이트[di(secbutyl)peroxydicarbonate], 디(이소프로필)퍼옥시디카보네이트[di(isopropyl)peroxydicarbonate], 디(시클로헥실)퍼옥시디카보네이트[di(cyclohexyl)peroxydicarbonate], 디(세틸)퍼옥시디카보네이트[di(cetyl)peroxydicarbonate], 디(n-프로필)퍼옥시디카보네이트[di(npropyl)peroxydicarbonate] 등과 같은 퍼옥시카보네이트 등이 있다. 상기 중합 개시제의 상업적인 상품으로는 Dupont사의 Vazo 52G, Vazo 64G, Vazo 67G, Vazo 88G 등이 있고, 개시제의 선택은 개시제의 각 온도별 반감기(Half life time)와 유기 용매의 끓는점(Boiling point) 등을 고려하여 선택한다. A radical polymerization initiator used for polymerizing a phosphorylcholine compound or copolymerizing a phosphorylcholine compound and a monomer having a hydroxyl group and an unsaturated group is, for example, azobisisobutyronitrile (AIBN), azobisdimethyl Azo initiators such as valenzonitrile, azo initiators, benzoyl peroxide, lauroyl peroxide, potassium persulfate, di (2-ethylhexyl) peroxydicarbonate [di ( 2ethylhexyl) peroxydicarbonate], di (sec-butyl) peroxydicarbonate] di (isopropyl) peroxydicarbonate] di (isopropyl) peroxydicarbonate] di (cyclohexyl) peroxydicarbonate peroxydicarbonate], di (cetyl) peroxydicarbonate, di (n-propyl) peroxydicarbonate There is a peroxycarbonate, etc., such as. Commercial products of the polymerization initiators include Duzot's Vazo 52G, Vazo 64G, Vazo 67G, Vazo 88G, etc., and the selection of the initiator includes a half life time of each temperature of the initiator and a boiling point of the organic solvent. Choose in consideration of.
한편, 중합 반응시 용매가 사용될 수 있으며, 중합 방법에 따라 적절한 용매가 선택된다. 유기 용제를 반응 매질로 사용하는 현탁 중합, 역상 에멀젼 중합, 침전 중합 또는 물을 반응 매질로 사용하는 용액 중합 등 다양한 방법으로 제조가 가능하다. 용매는 제한되지 않으나 단량체 총중량 대비 1~30배 중량비로 사용될 수 있다. 유기 용매로는 예를 들면 톨루엔, 벤젠, 시클로헥산, 에틸아세테이트, n-헥산, 에탄올, n-프로판올, 이소프로판올, t-부틸알코올, 메틸 에틸 케톤 등이 있으며, 이 중 하나를 선택하여 사용할 수도 있고, 1개 이상의 유기 용매를 적당량 혼합하여 사용한다. 예를 들면 1:99에서 99:1의 중량비로 혼합한 혼합용매로도 사용이 가능하다. Meanwhile, a solvent may be used in the polymerization reaction, and an appropriate solvent is selected according to the polymerization method. It can be prepared by various methods such as suspension polymerization using an organic solvent as a reaction medium, reverse phase emulsion polymerization, precipitation polymerization or solution polymerization using water as a reaction medium. The solvent is not limited but may be used in a 1 to 30 times weight ratio to the total weight of the monomers. Organic solvents include, for example, toluene, benzene, cyclohexane, ethyl acetate, n-hexane, ethanol, n-propanol, isopropanol, t-butyl alcohol, methyl ethyl ketone, and the like. At least one organic solvent is mixed and used in an appropriate amount. For example, it can be used as a mixed solvent mixed in a weight ratio of 1:99 to 99: 1.
포스포릴콜린계 화합물을 중합하거나, 히드록시기와 불포화기를 갖는 단량체를 함께 공중합함에 있어서, 추가적인 단량체가 더 사용되어 공중합될 수 있으며, 제한되지 않는다. 일례로 메틸 (메타)아크릴레이트, 에틸 (메타)아크릴레이트, n-부틸 (메타)아크릴레이트, 라우릴 (메타)아크릴레이트, 스테아릴 (메타)아크릴레이트, 2-에틸헥실 (메타)아크릴레이트, 및 시클로헥실 (메타)아크릴레이트 등의 (메타)아크릴계 단량체를 들 수 있다. 또한, 필요에 따라 적당량의 가교제를 더 포함할 수 있으며 제한되지 않는다. 가교제로는 예를 들면 에틸렌 글리콜 디아크릴레이트(ethylene glycol diacrylate), 에틸렌 글리콜 디메타크릴레이트(ethylene glycol dimethacrylate), 프로필렌 글리콜 디아크릴레이트(propylene glycol diacrylate), 프로필렌 글리콜 디메타크릴레이트(propylene glycol dimethacrylate), 부틸렌 글리콜 디아크릴레이트(butylene glycol diacrylate), 부틸렌 글리콜 디메타크릴레이트(butylene glycol dimethacrylate), 헥실렌 글리콜 디아크릴레이트(hexylene glycol diacrylate), 헥실렌 클리콜 디메타크릴레이트(hexylene glycol dimethacrylate), 디에틸렌 글리콜 디아크릴레이트(diethylene glycol diacrylate), 디에틸렌 글리콜 디메타크릴레이트(diethylene glycol dimethacrylate), 트리에틸렌 글리콜 디아크릴레이트(triethylene glycol diacrylate), 트리에틸렌 글리콜 디메타크릴레이트(triethylene glycol dimethacrylate), 테트라에틸렌 글리콜 디아크릴레이트(tetraethylene glycol diacrylate), 테트라에틸렌 글리콜 디메타크릴레이트(tetraethylene glycol dimethacrylate), 알릴 아크릴레이트(allyl acrylate), 알릴 메타크릴레이트(allyl methacrylate), 메타알릴 아크릴레이트(methallyl acrylate), 알릴 에타크릴레이트(allyl ethacrylate), 에타알릴 아크릴레이트(ethallyl acrylate), 메타알릴 메타크릴레이트(methallyl methacrylate), 디알릴 프탈레이트(diallyl phthalate), 디알릴 말레이트(diallyl maleate), 디알릴 석시네이트(diallyl succinate), 트리아릴 포스페이트(triallyl phosphate), 디알릴 옥살레이트(diallyl oxalate), 디알릴말로네이트(diallyl malonate), 디알릴 시트레이트(diallyl citrate), 디알릴 푸마레이트(diallyl fumarate), 디비닐 벤젠(divinyl benzene), 트리비닐 벤젠(trivinyl bezene), 비닐 크로토네이트(vinyl crotonate), N,N-메틸렌-비스-아크릴아마이드(N,N-methylene-bis-acrylamide), 트리메틸올프로판 디알릴 에테르(trimethylolpropane diallyl ether) 또는 트리메틸올프로판 트리알릴 에테르(trimethylolpropane triallyl ether), 디알릴 펜타에리쓰리톨 에테르(diallyl pentaerythritol ether), 트리알릴 펜타에리쓰리톨 에테르(triallyl pentaerythritol ether), 테트라알릴 펜타에리쓰리톨 에테르(tetraallyl pentaerythritol ether), 디알릴 수크로오스 에테르(diallyl sucrose ether), 트리알릴 수크로오스 에테르(triallyl sucrose ether), 또는 테트라알릴 수크로오스 에테르(tetraallyl sucrose ether), 펜타알릴 수크로오스 에테르(pentaallyl sucroseether), 헥사알릴 수크로오스 에테르(hexaallyl sucrose ether) 등이 있고, 이들을 단독 또는 혼합하여 사용할 수 있다.In polymerizing a phosphorylcholine compound or copolymerizing a monomer having a hydroxy group and an unsaturated group together, an additional monomer may be further used and copolymerized, but is not limited. For example methyl (meth) acrylate, ethyl (meth) acrylate, n-butyl (meth) acrylate, lauryl (meth) acrylate, stearyl (meth) acrylate, 2-ethylhexyl (meth) acrylate And (meth) acrylic monomers such as cyclohexyl (meth) acrylate. In addition, an appropriate amount of a crosslinking agent may be further included as necessary, and is not limited. Examples of the crosslinking agent include ethylene glycol diacrylate, ethylene glycol dimethacrylate, propylene glycol diacrylate, and propylene glycol dimethacrylate. ), Butylene Glycol Diacrylate, Butylene Glycol Dimethacrylate, Hexylene Glycol Dimethacrylate, Hexylene Glycol Dimethacrylate (hexylene Glycol Dimethacrylate) dimethacrylate, diethylene glycol diacrylate, diethylene glycol dimethacrylate, triethylene glycol diacrylate, triethylene glycol dimethacrylate (triethylene glycol dimethacrylate), tetraethylene glycol dike Tetraethylene glycol diacrylate, tetraethylene glycol dimethacrylate, allyl acrylate, allyl methacrylate, methallyl acrylate, allyl acrylate (allyl ethacrylate), ethallyl acrylate, methallyl methacrylate, diallyl phthalate, diallyl maleate, diallyl succinate, Triallyl phosphate, diallyl oxalate, diallyl malonate, diallyl citrate, diallyl citrate, diallyl fumarate, divinyl benzene ), Trivinyl bezene, vinyl crotonate, N, N-methylene-bis-acrylamide, N, N-methylene-bis-acrylamide Methylolpropane diallyl ether or trimethylolpropane triallyl ether, diallyl pentaerythritol ether, triallyl pentaerythritol ether, Tetraallyl pentaerythritol ether, diallyl sucrose ether, trially sucrose ether, or tetraallyl sucrose ether, pentaallyl sucrose ether, pentaallyl sucrose ether sucroseether, hexaallyl sucrose ether, and the like, and these may be used alone or in combination.
이렇게 포스포릴콜린계 그룹을 갖는 중합체 또는 포스포릴콜린계 그룹 및 히드록시기를 갖는 중합체를 제조한 후 기존 봉합사 원료인 단량체(파라디옥사논 등)와 반응시킴으로써 봉합사 신규 원료인 공중합체를 얻을 수 있다. In this way, a polymer having a phosphorylcholine group or a polymer having a phosphorylcholine group and a hydroxy group is prepared, and then reacted with a monomer (paradioxanone, etc.), which is an existing suture raw material, to obtain a new suture raw material copolymer.
본 발명의 공중합체는 특히 빠른 흡수성을 갖는 단사형(monofilament) 봉합사로 사용되는 것이 합사형태(multifilament)의 봉합사로 사용되는 것에 비해 조직의 상처가 적고 감염율이 낮게 되므로 단사형 봉합사로 사용되는 것이 바람직하다.In particular, the copolymer of the present invention is preferably used as a monofilament suture because it is used as a monofilament suture having a fast absorbency, so that the wound of the tissue is less and the infection rate is lower than that of a multifilament suture. Do.
본 발명의 공중합체를 이용한 단사형 봉합사의 직선 강력(tensile strength)는 45,000 psi 이상이고, 바람직하게는 45,000 내지 70,000 psi이며, 보다 바람직하게는 49,000 내지 53,000 psi으로 나타낼 수 있다. 본 발명 봉합사의 매듭 강력(knot-pull strength)은 25,000 psi 이상이고, 바람직하게는 30,000 내지 50,000 psi이며, 보다 바람직하게는 30,000 내지 33,000 psi일 수 있다. 본 발명 봉합사의 모듈러스는 180,000 psi 이하이며, 바람직하게는 30,000 내지 180,000psi일 수 있다. The linear strength of the single yarn suture using the copolymer of the present invention is 45,000 psi or more, preferably 45,000 to 70,000 psi, and more preferably 49,000 to 53,000 psi. The knot-pull strength of the suture of the present invention may be at least 25,000 psi, preferably 30,000 to 50,000 psi, and more preferably 30,000 to 33,000 psi. The modulus of the suture of the present invention is 180,000 psi or less, preferably 30,000 to 180,000 psi.
다음으로, 본 발명의 일실시예에 따른 봉합사는 다음의 방법을 통해 제조되는 봉합사일 수 있다. 즉, 기존의 봉합사 원료와 포스포릴콜린 유사기 함유 화합물을 용융 혼합한 뒤 방사함으로써 봉합사를 제조할 수 있다.Next, the suture according to an embodiment of the present invention may be a suture manufactured through the following method. That is, a suture may be manufactured by melt-mixing and spinning a conventional suture raw material and a phosphorylcholine like group-containing compound.
일례로, 크게 네 공정을 거쳐 완성되는 바, 폴리디옥사논 등의 봉합사 원료를 용융시켜 겔상태로 만든 후 포스포릴콜린 유사기 함유 화합물과 혼합하여 용융 혼합되는 용융 및 혼합공정과, 용융체 상태의 원료를 가압하여 가압조를 통해 방사구금 측으로 압출하는 압출공정과, 상기 가압조로부터 공급된 원료는 방사금구를 통해 실의 형태로 강하게 압출되는 방사공정과, 방사된 실을 연신장치를 이용하여 연신함으로써 인장강도와 탄성이 증대되도록 하는 연신공정으로 구성되어, 폴리디옥사논과 포스포릴콜린 유사기 함유 화합물이 혼합된 봉합사를 제조할 수 있다.For example, the bar is completed through four steps, and the suture raw material such as polydioxanone is melted into a gel state and then mixed with a phosphorylcholine-like group-containing compound to be melt mixed and melted. An extrusion process of pressurizing the raw material and extruding it to the spinneret side through the pressurizing tank, and a spinning process of the raw material supplied from the pressurizing tank being strongly extruded in the form of a thread through the spinneret, and stretching the spun yarn using a drawing apparatus. By the stretching process to increase the tensile strength and elasticity, it is possible to produce a suture mixed with a polydioxanone and a phosphoryl choline-like group-containing compound.
여기서, 상기 포스포릴콜린 유사기 함유 화합물은 전술한 MPC 등의 포스포릴콜린계 화합물이거나, MPC 등의 포스포릴콜린계 화합물의 중합체이거나, 히드록시기가 존재하는 불포화기 단량체와 함께 공중합한 공중합물일 수 있다. 이에 대한 설명은 충분히 전술하였으므로, 설명을 생략한다. 특히, 포스포릴콜린 유사기 함유 화합물에 히드록시기가 존재하는 경우 히드록시기와 반응 가능한 반응기(일례로는, 디옥사논, 카르보닐기 등)가 봉합사에 존재하는 경우 이와 반응함으로써 두 성분이 보다 화학적으로 강하게 결합될 수 있다.The phosphorylcholine-like group-containing compound may be a phosphorylcholine-based compound such as MPC, a polymer of a phosphorylcholine-based compound such as MPC, or a copolymer copolymerized with an unsaturated group monomer having a hydroxy group. . Since the description thereof has been sufficiently described above, the description thereof will be omitted. In particular, when a hydroxyl group is present in the phosphorylcholine-like group-containing compound, a reactor capable of reacting with a hydroxyl group (for example, a dioxanone, a carbonyl group, etc.) is reacted with the suture, thereby reacting the two components more chemically. Can be.
다음으로, 본 발명의 일실시예에 따른 봉합사는 봉합사용 섬유의 표면을 코팅, 개질하여 제조된 봉합사일 수 있다. 즉, 포스포릴콜린 유사기 함유 화합물이 용매에 용해된 용액에 봉합사용 섬유를 합침(침지)하여 표면을 코팅함으로써 생체 적합성 봉합사로 표면 개질하는 것일 수 있다. 여기서 포스포릴콜린 유사기 함유 화합물이란, 전술한 MPC 등의 포스포릴콜린계 화합물이거나, MPC 등의 포스포릴콜린계 화합물의 중합체이거나, 히드록시기가 존재하는 불포화기 단량체와 함께 공중합한 공중합물일 수 있다. 이에 대한 설명은 충분히 전술하였으므로, 설명을 생략한다. 특히, 포스포릴콜린 유사기 함유 화합물에 히드록시기가 존재하는 경우 히드록시기와 반응 가능한 반응기(일례로는, 디옥사논, 카르보닐기 등)가 봉합사에 존재하는 경우 이와 반응함으로써 두 성분이 보다 화학적으로 강하게 결합될 수 있다.Next, the suture according to an embodiment of the present invention may be a suture manufactured by coating and modifying the surface of the suture fiber. That is, the phosphorylcholine-like group-containing compound may be surface modified with a biocompatible suture by coating (surface) the surface of the suture fibers by impregnating (immersing) the fibers for suture in a solution dissolved in a solvent. The phosphorylcholine-like group-containing compound may be a phosphorylcholine-based compound such as MPC described above, a polymer of phosphorylcholine-based compound such as MPC, or a copolymer copolymerized with an unsaturated group monomer having a hydroxy group. Since the description thereof has been sufficiently described above, the description thereof will be omitted. In particular, when a hydroxyl group is present in the phosphorylcholine-like group-containing compound, a reactor capable of reacting with a hydroxyl group (for example, a dioxanone, a carbonyl group, etc.) is reacted with the suture, thereby reacting the two components more chemically. Can be.
사용되는 용매로는 제한되지 않으며, 일례로는 물, 톨루엔, 벤젠, 시클로헥산, 에틸아세테이트, n-헥산, 에탄올, n-프로판올, 이소프로판올, t-부틸알코올, 메틸 에틸 케톤 등이 있으며, 이 중 하나를 선택하여 사용할 수도 있고, 1개 이상의 유기 용매를 적당량 혼합하여 사용한다. The solvent used is not limited, and examples thereof include water, toluene, benzene, cyclohexane, ethyl acetate, n-hexane, ethanol, n-propanol, isopropanol, t-butyl alcohol, methyl ethyl ketone, and the like. One may be used and one or more organic solvents may be mixed and used in an appropriate amount.
상기 포스포릴콜린 유사기 함유 화합물의 용액의 농도는 4 내지 12 중량% 범위내가 바람직하다. 상기 농도 범위 미만에서는 침지 대비 효과가 미미하고, 상기 범위를 초과하는 경우 봉합사 물성에 문제될 수 있다.The concentration of the solution of the phosphorylcholine like group-containing compound is preferably in the range of 4 to 12% by weight. If the concentration range is less than the immersion effect is insignificant, if it exceeds the range may be a problem in the suture properties.
상기 침지 조건은 제한되지 않으나 봉합사 섬유를 포스포릴콜린 유사기 함유 용액에 12 내지 36시간 동안 1회 침지하는 것이 후술하는 실시예에서 보듯이 좋다.The immersion conditions are not limited, but immersion of the suture fibers in the solution containing phosphorylcholine like group once for 12 to 36 hours may be good as shown in the following examples.
이하 실시예를 통해 본 발명을 보다 상세하게 설명한다.The present invention will be described in more detail with reference to the following Examples.
<실시예 1-4> 침지 코팅 농도의 최적화 Example 1-4 Optimization of Immersion Coating Concentration
하기 표 1과 같이, 농도별 poly 2-Methacryloyloxyethyl Phosphoryl Choline (PMPC) 수용액을 준비하여 PDO(폴리디옥사논) 봉합사를 침지시켜 농도 최적화 시험을 하였다. 이때 사용하는 봉합사의 직경은 1mm이고 5cm의 일정한 길이로 하루 동안 침지시킨 후 온풍건조하였다. As shown in Table 1, concentration of poly 2-Methacryloyloxyethyl Phosphoryl Choline (PMPC) aqueous solution was prepared by immersing the PDO (polydioxanone) suture was tested for concentration optimization. At this time, the suture used was 1mm in diameter and immersed in a constant length of 5cm for one day and then warm air dried.
<비교예 1> 코팅하지 않은 PDO의 침지 코팅 Comparative Example 1 Immersion Coating of Uncoated PDO
상기 실시예와 동일한 과정을 거치되, PMPC가 포함되지 않은 수용액을 사용하여 봉합사를 침지시켰다.The same process as in the above example, but the suture was immersed using an aqueous solution that does not contain PMPC.
표 1
PMPC수용액 농도(wt%) 침지시간(시간)
비교예 1 0 24
실시예 1 4 24
실시예 2 5 24
실시예 3 7.5 24
실시예 4 11 24
Table 1
PMPC aqueous solution concentration (wt%) Immersion time (hours)
Comparative Example 1 0 24
Example 1 4 24
Example 2 5 24
Example 3 7.5 24
Example 4 11 24
<실험예 1>Experimental Example 1
실시예 1~4 및 비교예로부터 얻어진, 침지된 봉합사의 항균성을 시험하고자 MPC 코팅된 봉합사에 부착된 황색포도상구균(Staphylococcus aureus)의 콜로니를 관찰함으로써 미생물 부착시험을 실시하였다. Staphylococcus aureus ATCC6538 (포도상구균)을 TSA(tryptic soy agar) 평판배지에 32?로 24시간 배양한 후 백금이(Platiunm tool)를 이용하여 PBS(phosphate boffered saline) 10ml 에 Staphylococcus aureus ATCC6538 cell 을 ml당 10?이 되게 분산시킨다. 이 서스펜젼(suspension)에 실시예 1~4 및 비교예의 봉합사를 담가두고 30분간 32?에 방치한 후 봉합사를 꺼내어 PBS로 30초간 세척한 다음 여과지에 놓아 여분의 PBS 를 제거한다. 봉합사를 TSA plate에 올려 놓은 다음 32? 배양기에 넣어 24시간-48시간 동안 배양하면서 생성되는 콜로니를 관찰하였다.The microbial adhesion test was performed by observing colonies of Staphylococcus aureus attached to MPC coated sutures to test the antimicrobial activity of the immersed sutures obtained in Examples 1-4 and Comparative Examples. After incubating the Staphylococcus aureus ATCC6538 (S. aureus) for 24 hours at 32 ° on a tryptic soy agar (TSA) plate for 24 hours, using the Platiunm tool, 10 ml of Staphylococcus aureus ATCC6538 cells in 10 ml of phosphate boffered saline (PBS) Disperse The sutures of Examples 1-4 and Comparative Example were soaked in this suspension and left at 32 ° C for 30 minutes, and then the sutures were taken out, washed with PBS for 30 seconds, and placed on a filter paper to remove excess PBS. Put the sutures on the TSA plate, and then 32? Colonies generated during incubation for 24 to 48 hours were observed in the incubator.
그 결과를 도 1에 나타내었다(a: 4 wt% PMPC수용액, b: 5 wt% PMPC수용액, c: 7.5 wt% PMPC수용액, d: 11 wt% PMPC수용액). 미생물 부착성 시험 결과 실시예 2(5wt% PMPC수용액으로 코팅한 봉합사)의 미생물 부착성이 가장 적음을 관찰할 수 있었다. 도 2는 비교예에 의해 제조된 봉합사를 실험예 1과 동일한 방식으로 배양하여 나타난 결과를 나타낸 것이다. 실시예에 비하여 미생물 부착성이 높은 것을 확인할 수 있다. The results are shown in Figure 1 (a: 4 wt% aqueous solution of PMPC, b: 5 wt% aqueous solution of PMPC, c: 7.5 wt% aqueous solution of PMPC, d: 11 wt% aqueous solution of PMPC). As a result of the microbial adhesion test, it was observed that Example 2 (the suture coated with 5 wt% PMPC aqueous solution) had the least microbial adhesion. Figure 2 shows the results shown by incubating the suture prepared by the comparative example in the same manner as Experimental Example 1. It can be confirmed that the microbial adhesion is high compared to the embodiment.
<실시예 5-7> 침지시간 및 침지횟수 최적화 <Example 5-7> Immersion time and immersion frequency optimization
침지 코팅 농도인 5wt% PMPC 수용액을 사용하여 <표 2>와 같이 침지시간 및 침지횟수를 달리하여 코팅한 후 미생물 부착시험을 실시하여 최적의 침지방법을 확인하였다. 미생물 부착성 시험은 실시예 1-4로 실시한 방법과 동일하게 하였다.Using the 5wt% PMPC aqueous solution, which is the immersion coating concentration, coating was performed by varying the immersion time and the number of immersion times as shown in <Table 2>, and then the microbial adhesion test was performed to confirm the optimum immersion method. The microorganism adhesion test was carried out in the same manner as in Example 1-4.
표 2
침지시간 침지횟수
실시예 5 1일 1회
실시예 6 30분 5회
실시예 7 30분 10회
TABLE 2
Immersion time Immersion count
Example 5 1 day 1 time
Example 6 30 minutes 5 times
Example 7 30 minutes 10th
그 결과를 도 3에 나타내었다(a: 실시예 5, b: 실시예 6, c: 실시예 7). 실험결과, 짧게 여러 번 반복 침지 코팅하는 것보다 장시간 1회 코팅하는 것이 균일한 코팅성능과 부착성을 보여주었다. The results are shown in Fig. 3 (a: Example 5, b: Example 6, c: Example 7). As a result of the experiment, coating once in a long time than uniform dip coating repeatedly showed uniform coating performance and adhesion.
한편, 최적화된 농도와 침지방법을 통해 코팅된 봉합사의 코팅 균일성은 주사전자현미경(SEM)으로 촬영하였고 90% 이상 균일한 코팅이 이루어졌음을 확인하였다. Meanwhile, the coating uniformity of the suture coated by the optimized concentration and immersion method was photographed by scanning electron microscopy (SEM), it was confirmed that more than 90% uniform coating was made.
이상에서와 같이 본 발명을 상기의 실시예를 통해 설명하였지만 본 발명이 반드시 여기에만 한정되는 것은 아니며 본 발명의 범주와 사상을 벗어나지 않는 범위 내에서 다양한 변형실시가 가능함은 물론이다. 또한, 본 발명의 본질적인 범주를 벗어나지 않고서도 많은 변형을 실시하여 특정 상황 및 재료를 본 발명의 교시내용에 채용할 수 있다. 따라서, 본 발명의 보호범위는 본 발명을 실시하는데 계획된 최상의 양식으로서 개시된 특정 실시 태양으로 국한되는 것이 아니며, 본 발명에 첨부된 특허청구의 범위에 속하는 모든 실시 태양을 포함하는 것으로 해석되어야 한다.Although the present invention has been described through the above embodiments as described above, the present invention is not necessarily limited thereto, and various modifications can be made without departing from the scope and spirit of the present invention. In addition, many modifications may be made to adapt a particular situation and material to the teachings of the invention without departing from the essential scope thereof. Therefore, the protection scope of the present invention should not be construed as limited to the specific embodiments disclosed as the best mode contemplated for carrying out the invention, but including all embodiments falling within the scope of the claims appended hereto.
본 발명에 따른 봉합사는 인장강도, 생체 흡수성이 우수할 뿐만 아니라 포스포릴콜린 유사기를 함유함으로써 생체 적합성, 항균성이 특히 우수하여 봉합사의 용도로 사용될 수 있어 산업적으로 유용하다.The suture according to the present invention is not only excellent in tensile strength and bioabsorption, but also contains phosphorylcholine-like groups, so that the suture is particularly excellent in biocompatibility and antibacterial properties, and thus it is industrially useful.

Claims (7)

  1. 봉합사용 섬유;Suture fiber;
    상기 섬유에 존재하는 포스포릴콜린 유사기 함유 화합물;을 포함하여 이루어진 봉합사.Suture comprising a; phosphoryl choline-like group-containing compound present in the fiber.
  2. 제1항에 있어서, The method of claim 1,
    상기 포스포릴콜린 유사기 함유 화합물은 하기 화학식 1의 화합물 또는 그 중합체인 것을 특징으로 하는 봉합사.The phosphorylcholine like group-containing compound is a suture characterized in that the compound of formula (1) or a polymer thereof.
    [화학식 (1)][Formula (1)]
    Figure PCTKR2014011998-appb-I000004
    Figure PCTKR2014011998-appb-I000004
    (상기 화학식 (1)에서 X는 2가의 유기잔기를 나타내고, Z는 수소원자 또는 R5-O-CO-(여기서, R5는 수소원자, 탄소수 1~10의 알킬기 또는 탄소수 1~10의 히드록시알킬기를 나타낸다)를 나타내고, Y는 탄소수 1~20의 알킬렌옥시기를 나타낸다. 또한, R1은 수소원자 또는 탄소수 1~5의 탄화수소기를 나타내고, R2, R3 및 R4는 동일 또는 다른 기로서, 수소원자, 탄소수 1~6의 탄화수소기 또는 히드록시 탄화수소기를 나타낸다. 또한, m은 1~20의 정수이고, n은 2~5의 정수이다)(In Formula (1), X represents a divalent organic residue, Z represents a hydrogen atom or R 5 -O-CO-, where R 5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or a hydroxide having 1 to 10 carbon atoms. Oxyalkyl group), Y represents an alkyleneoxy group having 1 to 20 carbon atoms, R 1 represents a hydrogen atom or a hydrocarbon group of 1 to 5 carbon atoms, and R 2 , R 3 and R 4 are the same or different. As a group, a hydrogen atom, a C1-C6 hydrocarbon group, or a hydroxy hydrocarbon group is represented, m is an integer of 1-20, n is an integer of 2-5)
  3. 제1항에 있어서, The method of claim 1,
    상기 포스포릴콜린 유사기 함유 화합물은 하기 화학식 1의 화합물과 불포화기 존재 단량체의 공중합체인 것을 특징으로 하는 봉합사.The phosphorylcholine-like group-containing compound is a suture characterized in that the copolymer of the compound of formula 1 and a monomer having an unsaturated group.
    [화학식 (1)][Formula (1)]
    Figure PCTKR2014011998-appb-I000005
    Figure PCTKR2014011998-appb-I000005
    (상기 화학식 (1)에서 X는 2가의 유기잔기를 나타내고, Z는 수소원자 또는 R5-O-CO-(여기서, R5는 수소원자, 탄소수 1~10의 알킬기 또는 탄소수 1~10의 히드록시알킬기를 나타낸다)를 나타내고, Y는 탄소수 1~20의 알킬렌옥시기를 나타낸다. 또한, R1은 수소원자 또는 탄소수 1~5의 탄화수소기를 나타내고, R2, R3 및 R4는 동일 또는 다른 기로서, 수소원자, 탄소수 1~6의 탄화수소기 또는 히드록시 탄화수소기를 나타낸다. 또한, m은 1~20의 정수이고, n은 2~5의 정수이다)(In Formula (1), X represents a divalent organic residue, Z represents a hydrogen atom or R 5 -O-CO-, where R 5 represents a hydrogen atom, an alkyl group having 1 to 10 carbon atoms or a hydroxide having 1 to 10 carbon atoms. Oxyalkyl group), Y represents an alkyleneoxy group having 1 to 20 carbon atoms, R 1 represents a hydrogen atom or a hydrocarbon group of 1 to 5 carbon atoms, and R 2 , R 3 and R 4 are the same or different. As a group, a hydrogen atom, a C1-C6 hydrocarbon group, or a hydroxy hydrocarbon group is represented, m is an integer of 1-20, n is an integer of 2-5)
  4. 제1항에 있어서, The method of claim 1,
    상기 포스포릴콜린 유사기 함유 화합물은 상기 섬유 100 중량 대비 8 내지 15 중량부 포함되는 것을 특징으로 하는 봉합사. The phosphorylcholine like group-containing compound is suture characterized in that it comprises 8 to 15 parts by weight based on 100 weight of the fiber.
  5. 포스포릴콜린 유사기 함유 화합물의 수용액과 봉합사용 섬유를 준비하는 단계;Preparing an aqueous solution of a phosphorylcholine like group-containing compound and a suture fiber;
    상기 포스포릴콜린 유사기 함유 화합물의 용액에 봉합사용 섬유를 침지하는 단계; 및Immersing suture fibers in a solution of the phosphorylcholine like group-containing compound; And
    침지된 섬유를 건조하는 단계;를 포함하여 이루어진 봉합사의 제조방법.Drying the immersed fiber; Method of producing a suture comprising a.
  6. 제5항에 있어서,The method of claim 5,
    상기 포스포릴콜린 유사기 함유 화합물의 용액의 농도는 4 내지 12 중량% 범위내인 것을 특징으로 하는 봉합사의 제조방법.The concentration of the solution of the phosphoryl choline-like group-containing compound is characterized in that in the range of 4 to 12% by weight.
  7. 제5항에 있어서,The method of claim 5,
    상기 침지하는 단계는 봉합사용 섬유를 12 내지 36시간 동안 1회 침지하는 것을 특징으로 하는 봉합사의 제조방법.The dipping step is a method of producing a suture, characterized in that immersing the suture fibers once for 12 to 36 hours.
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WO2021117513A1 (en) * 2019-12-11 2021-06-17 ケイセイ医科工業株式会社 Medical suturing thread

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