KR20060110190A - Biomaterial - coated dental implant and the coating method - Google Patents

Biomaterial - coated dental implant and the coating method Download PDF

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KR20060110190A
KR20060110190A KR1020050032456A KR20050032456A KR20060110190A KR 20060110190 A KR20060110190 A KR 20060110190A KR 1020050032456 A KR1020050032456 A KR 1020050032456A KR 20050032456 A KR20050032456 A KR 20050032456A KR 20060110190 A KR20060110190 A KR 20060110190A
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bioactive material
implant
intermediate reactor
reactor layer
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엄태관
김재호
오상근
김태일
최성욱
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오스템임플란트 주식회사
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0012—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy
    • A61C8/0013—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy with a surface layer, coating
    • A61C8/0015—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy with a surface layer, coating being a conversion layer, e.g. oxide layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
    • A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
    • A61C8/0012—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy
    • A61C8/0013—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy with a surface layer, coating
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/28—Materials for coating prostheses
    • A61L27/34—Macromolecular 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Dermatology (AREA)
  • Transplantation (AREA)
  • Dentistry (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Ceramic Engineering (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Inorganic Chemistry (AREA)
  • Composite Materials (AREA)
  • Materials Engineering (AREA)
  • Materials For Medical Uses (AREA)
  • Dental Preparations (AREA)

Abstract

Provided are a dental implant and a method for coating of the implant with bioactive material which can increase a bond of peptide and osteoblast and maximize an activity of the bioactive material by controlling a distribution density or orientation of the bioactive material. The dental implant(3) comprises a matrix material and a bioactive material which are fixed on a base layer of middle reaction formed on active film on circumference of the implant by chemical covalent bond. The bioactive material is mixed with the matrix material in predetermined concentration. The implant has a distribution and an orientation on its circumference so as to facilitate it to effectively bond with osteoblast. The method for coating of bioactive material comprises the steps of chemically activating an oxidation film on circumference of the implant by using mixed acid solution of hydrogen peroxide and sulfuric acid, ozone, and plasma, so as to form OH group on the oxidation film(forming step of an active film(31)), forming a base layer of middle reaction on the active film(31) by reacting any one selected from the group a silane group having (CH2)n(with one end being bonded to Si-(-R)3, and the other end being bonded to any one selected from the group consisting of amine group, carboxyl group, and aldehyde group), or a phosphate group having (CH2)n(with one end being bonded to PO4 and the other end being bonded to any one selected from the group consisting of amine group, carboxyl group, and aldehyde group) with the active film to form a base layer of middle reaction, and appropriately mixing the matrix material(32) and the bioactive material(34) with controlled concentration, to form a mixture, applying the mixture on the base layer(33), and a fixing the matrix material(32) and the bioactive material(34) on the base layer(33) by amide reaction of the materials(32,34) with amine or carboxyl group of the base layer(33), and imine reaction of the materials(32,34) with aldehyde group of the base layer(33).

Description

생체활성물질이 코팅된 치과용 임프란트와 그 코팅방법{Biomaterial - coated Dental Implant and the Coating Method}Dental implant coated with bioactive material and its coating method {Biomaterial-coated Dental Implant and the Coating Method}

도 1은 종래의 생체활성물질이 코팅된 치과용 임프란트 개략 단면도.1 is a schematic cross-sectional view of a dental implant coated with a conventional bioactive material.

도 2는 본 발명의 일실시예에 따른 생체활성물질이 코팅된 치과용 임프란트의 개략 단면도.Figure 2 is a schematic cross-sectional view of a dental implant coated with a bioactive material according to one embodiment of the present invention.

도 3은 본 발명의 일실시예에 따른 생체활성물질을 코팅하는 공정을 도시하는 흐름도.3 is a flow chart illustrating a process of coating a bioactive material in accordance with one embodiment of the present invention.

도 4a는 본 발명의 일실시예에 따른 치과용 임프란트의 표면에 활성막이 형성된 상태를 나타내는 개략도.Figure 4a is a schematic diagram showing a state in which the active film is formed on the surface of the dental implant according to an embodiment of the present invention.

도 4b는 치과용 임프란트의 활성막상에 실란기 또는 인산기를 이용해 중간반응기층을 형성하는 단계를 나타내는 개략도.Figure 4b is a schematic diagram showing the step of forming an intermediate reactor layer using a silane group or a phosphate group on the active membrane of the dental implant.

도 4c는 치과용 임프란트의 활성막상에 형성된 중간반응기층상에 매트릭스물질과 생체활성물질을 고정하는 단계를 나타내는 개략도.Figure 4c is a schematic diagram showing the step of fixing the matrix material and the bioactive material on the intermediate reactor layer formed on the active membrane of the dental implant.

도 4d는 생체활성물질이 코팅된 임프란트의 표면을 도시하는 개략도.4D is a schematic diagram showing the surface of an implant coated with a bioactive material.

도 5a는 본 발명의 다른 실시예에 따른 생체활성물질이 코팅된 치과용 임프란트에 있어서 앞서 도 4c에 도시된 중간반응기층상에 생체활성물질이 결합된 고분자물질을 고정하는 단계를 나타내는 개략도.Figure 5a is a schematic diagram showing the step of fixing the bioactive material bonded to the bioactive material on the intermediate reactor layer shown in Figure 4c in the dental implant coated bioactive material according to another embodiment of the present invention.

도 5b는 도 5a에 따른 생체활성물질이 코팅된 치과용 임프란트의 개략도.Figure 5b is a schematic view of the dental implant coated with the bioactive material according to Figure 5a.

본 발명은 그 외주면에 생체활성물질이 코팅된 치과용 임프란트와 그 코팅방법에 관한 것으로, 특히 치과용임프란트의 외주면상에 활성막을 형성하고 그 활성막상에 중간반응기층을 적층한 뒤 그 중간반응기층상에 매트릭스물질과 생체활성물질을 고정하거나 생체활성물질이 결합된 고분자물질을 고정함으로써 멸균과정 후에도 생체활성이 그대로 유지되어 유통과 보관이 용이할 뿐만 아니라 치과용임프란트와 생체활성물질간에 충분한 접착력을 확보함으로써 치과용 임프란트 시술시 골유착기간을 단축시킬 수 있는 치과용 임프란트와 그 코팅방법에 관한 것이다. The present invention relates to a dental implant coated with a bioactive material on the outer peripheral surface and a coating method thereof, in particular to form an active membrane on the outer peripheral surface of the dental implant and to deposit an intermediate reactor layer on the active membrane layer on the intermediate reactor layer By fixing the matrix material and the bioactive material on the substrate or by fixing the polymer material combined with the bioactive material, the bioactivity is maintained even after sterilization process, making it easy to distribute and store, and secure sufficient adhesion between the dental implant and the bioactive material. Thus, the present invention relates to a dental implant and a coating method thereof, which can shorten the bone adhesion period during the dental implant procedure.

임프란트란 상실된 인체 조직을 회복시켜 주는 대치물을 의미하는데, 치과에서는 일반적으로 상실된 치아의 치근(뿌리)을 대신할 수 있도록 자연치근이 빠져나간 치조골에 심어서 유착시킨 후 인공치아를 고정시켜 치아의 원래 기능을 회복하도록 하는 대치물을 의미한다.  Implant refers to a substitute that restores lost human tissue. In dentistry, the artificial tooth is fixed and implanted in the alveolar bone where the natural root has fallen so that it can replace the root (root) of the lost tooth. It means a substitute to restore function.

이러한 임프란트는 자연치근을 대신하므로 치조골에 식립된 후에는 안정적으로 골성장을 유도하여 치조골에 고정될 수 있어야 한다. 따라서, 골유착기간을 단축시키기 위하여 종래에는 임프란트의 표면상에 하이드로애퍼타이트(Hydroxyl Apatite)를 픽스츄어에 물리적방식으로 코팅하거나 펩티드와 같은 생체활성물질을 물리적방식으로 접착하는 방식을 사용하였다.Since such implants replace natural roots, they should be stably induced in the alveolar bone after being placed in the alveolar bone. Therefore, in order to shorten the bone adhesion period, conventionally, a method of physically coating a hydroapatite (Hydroxyl Apatite) on the surface of the implant to the fixture or physically bonding a bioactive material such as a peptide.

그러나, 하이드로애퍼타이트를 코팅하는 방식은 그 코팅층이 50㎛로 두꺼워 코팅층에 표면 크랙이 존재하거나 표면거칠기를 조절하기가 매우 난해하고 매식후에는 코팅층이 임프란트의 외주면에서 박리되어 임프란트가 치조골에서 빠지는 문제점을 유발하였다. However, in the method of coating hydroapatite, the coating layer is thick with 50㎛, so it is very difficult to control surface roughness or surface roughness in the coating layer, and after the implantation, the coating layer is peeled off the outer peripheral surface of the implant and the implant is removed from the alveolar bone. Induced.

또한, 펩티드와 같은 생체활성물질을 코팅하는 방식은 임프란트를 생체활성물질이 함유된 용액에 담구었다가 소정 시간동안 건조하는 것이어서, 도 1에 도시된 바와 같이 생체활성물질(24)이 임프란트(21)의 외주면상에 단순히 물리적으로 흡착되어 있을 뿐이다. 따라서, 치조골에 매식될 때 임프란트의 외주면에서 생체활성물질이 접착력 약화로 박리되는 경향이 많아서 생체활성물질이 안정적으로 임프란트에 결합될 수 없고 결국 골유착기능을 제대로 발휘할 수 없다는 문제점이 있었다. 또한 이와 같은 방식은 제조 공정 중에서 감마멸균과정을 거치는 동안 그리고 온도의 변화에 따라 생체활성물질의 성질이 변할 수 있고 유통이나 보관이 어려운 단점이 있었다. 또한, 생체활성물질의 표면농도조절이 되지 않아서, 생체활성 물질의 공간분포나 배향을 조절할 수 없고, 결국 조골세포(1)와 펩티드간의 결합성이 떨어지는 문제점도 있었다.In addition, the method of coating a bioactive material such as a peptide is to immerse the implant in a solution containing the bioactive material and to dry for a predetermined time, so that the bioactive material 24 is the implant 21 as shown in FIG. It is simply physically adsorbed on the outer circumferential surface of). Therefore, when the alveolar bone is buried, there is a tendency that the bioactive material is peeled off due to weakened adhesion on the outer circumferential surface of the implant, so that the bioactive material cannot be stably bonded to the implant and finally exhibits a bone adhesion function. In addition, this method has the disadvantage that the properties of the bioactive material can be changed during the gamma sterilization process in the manufacturing process and the temperature changes, and it is difficult to distribute or store. In addition, since the surface concentration of the bioactive material is not controlled, the spatial distribution and orientation of the bioactive material cannot be controlled, resulting in poor binding between the osteoblast (1) and the peptide.

또한, 앞서 설명한 방식이외에도, 임프란트 시술시에, 시술자가 생체활성물질을 임프란트의 표면에 대량 도포하여 사용하기도 하는데, 이와 같은 방식도 생체활성물질이 식립시 효과적으로 잔류하지 못하는 문제점을 가지고 있을 뿐만 아니라 도포의 균일성을 확보할 수 없어서, 효과적인 골재생이나 골유착 기능을 구현하지 못하며 오히려 시술비만 증가시킬 뿐이었다. In addition to the methods described above, during implantation, the operator may apply a large amount of bioactive material to the surface of the implant, and this method also has a problem in that the bioactive material does not remain effectively during implantation. Because it could not secure the uniformity of the body, effective bone regeneration or bone adhesion function could not be implemented, but rather only increased procedure cost.

본 발명은 앞서 본 종래기술의 문제점을 해결하기 위하여 안출된 것으로, 본 발명의 목적은, 그 활성막상에 중간반응기층을 적층한 뒤 그 중간반응기층상에 매트릭스물질과 생체활성물질을 화학적 공유결합으로 고정하거나 생체활성물질이 결합된 고분자물질을 고정함으로써 멸균과정 후에도 생체활성이 그대로 유지되어 유통과 보관이 용이할 뿐만 아니라 치과용임프란트와 생체활성물질간에 충분한 접착력을 확보함으로써 치과용 임프란트 시술시 골유착기간을 단축시킬 수 있는 치과용 임프란트와 그 코팅방법을 제공하는 것이다.The present invention has been made in order to solve the problems of the prior art, the object of the present invention is to stack the intermediate reactor layer on the active membrane, and then chemically bond the matrix material and the bioactive material on the intermediate reactor layer By fixing or fixing the polymer material combined with the bioactive material, the bioactivity is maintained even after sterilization process, so it is easy to distribute and store, and also secures sufficient adhesion between the dental implant and the bioactive material so that the bone adhesion during the dental implant procedure It is to provide a dental implant and a coating method that can shorten the period.

본 발명의 다른 목적은 생체활성물질의 분포밀도나 배향을 조절함으로써 펩티드와 조골세포간의 결합성을 높여 생체활성물질의 활성특성을 극대화할 수 있는 치과용 임프란트와 그 코팅방법을 제공하는 것이다.Another object of the present invention is to provide a dental implant and its coating method which can maximize the activity characteristics of the bioactive material by increasing the binding between the peptide and osteoblast by adjusting the distribution density or orientation of the bioactive material.

본 발명은 앞서 본 목적을 달성하기 위하여 다음과 같은 구성을 가진 실시예에 의해 구현된다. The present invention is implemented by the embodiment having the following configuration in order to achieve the above object.

본 발명의 제 1 실시예에 따르면, 본 발명의 치과용 임프란트는, 임프란트의 외주면상에 형성된 활성막상에 생성된 중간반응기층에 매트릭스물질과 생체활성물질을 화학적 공유결합으로 고정하여 형성되며, 상기 생체활성물질은 매트릭스물질과 소정의 농도로 혼합되어 있어 임프란트의 외주면상에서 조골세포와 효율적인 결합이 가능하도록 하는 분포공간과 배향을 가지는 것을 특징으로 한다.According to the first embodiment of the present invention, the dental implant of the present invention is formed by chemically covalently fixing a matrix material and a bioactive material on an intermediate reactor layer formed on an active film formed on the outer circumferential surface of the implant, The bioactive material is mixed with the matrix material at a predetermined concentration and has a distribution space and an orientation to enable efficient coupling with osteoblasts on the outer circumferential surface of the implant.

본 발명의 제 2 실시예에 따르면, 본 발명의 치과용 임프란트는, 임프란트의 외주면상에 형성된 활성막상에 생성된 중간반응기층에 생체활성물질이 결합된 고분자물질을 고정하여 형성되며, 상기 생체활성물질은 고분자물질에 의해 조골세포와 효율적인 결합이 가능하도록 하는 분포공간과 배향을 가지는 것을 특징으로 한다. According to a second embodiment of the present invention, the dental implant of the present invention is formed by fixing a polymer material in which a bioactive material is bonded to an intermediate reactor layer formed on an active membrane formed on an outer circumferential surface of the implant, wherein the bioactive The material is characterized by having a distribution space and orientation to enable efficient binding to osteoblasts by the polymer material.

본 발명의 제 3 실시예에 따르면, 본 발명의 치과용 임프란트는, 상기 제 1 실시예 내지 제 2 실시예 중 어느 한 항에 있어서, 상기 활성막은 임프란트의 외주면상에 OH기능기를 생성함으로써 형성되며, 상기 중간반응기층은 (CH2)n 일단에는 Si-(O-R)3이 그리고 타단에는 아민기, 카르복실기, 알데히이드기로 구성된 그룹으로부터 선택된 하나가 결합된 실란기를 상기 활성막과 실란화 반응을 통해 생성되거나 (CH2)n일단에는 PO4가 그리고 타단에는 아민기, 카르복실기, 알데히이드기로 구성된 그룹으로부터 선택된 하나가 결합된 인산기를 상기 활성막과 인산화 반응을 통해 생성되는 것을 특징으로 한다. According to a third embodiment of the present invention, the dental implant of the present invention is formed by producing an OH functional group on the outer circumferential surface of the implant according to any one of the first to second embodiments. The intermediate reactor layer is (CH 2 ) n At one end, Si- (OR) 3 and at the other end, a silane group bonded to one selected from the group consisting of an amine group, a carboxyl group, and an aldehyde group is generated through silanization with the active layer, or at one end of PO (CH 2 ) n The tetravalent and the other end is characterized in that a phosphate group bonded to one selected from the group consisting of an amine group, a carboxyl group, and an aldehyde group is produced through a phosphorylation reaction with the active membrane.

본 발명의 제 4 실시예에 따르면, 본 발명의 치과용 임프란트는, 상기 제 3 실시예에 있어서, 상기 매트릭스물질은 생체활성물질과 크기가 유사하며 일단에는 활성막의 OH기와 반응성을 가지는 아민기, 카르복실기와 알데히이드기로 구성된 그룹으로부터 선택된 하나를 가지며 타단에는 생체활성물질과 반응성이 없는 OH기와 CH3기로 구성된 그룹으로부터 선택된 하나를 가지는 단분자 또는 고분자물질이며, 상기 매트릭스물질과 생체활성물질은 중간반응기층의 아민기 또는 카르복실기와는 아미드반응을 통해 그리고 알데히드기와는 이민반응을 통해 중간반응기층에 화학적 공유결합을 통해 고정되는 것을 특징으로 한다. According to the fourth embodiment of the present invention, in the dental implant of the present invention, in the third embodiment, the matrix material is similar in size to the bioactive material, and at one end of the amine group having a reactivity with the OH group of the active membrane, It is a single molecule or a polymer having one selected from the group consisting of a carboxyl group and an aldehyde group and at the other end having one selected from the group consisting of an OH group and a CH 3 group which is not reactive with a bioactive material, and the matrix material and the bioactive material are intermediate The amine group or carboxyl group of the reactor layer is immobilized through chemical covalent bonds to the intermediate reactor layer through an amide reaction and an imine reaction with the aldehyde group.

본 발명의 제 5 실시예에 따르면, 본 발명의 치과용 임프란트는, 상기 제 3 실시예에 있어서, 상기 고분자물질은 폴리락티드와 카르복실산의 공중합 폴리머로서 그 일단에는 생체활성물질이 결합되어 있어서 정전기적 힘에 의해 중간반응기층상에 고정되는 것을 특징으로 한다.According to a fifth embodiment of the present invention, in the dental implant of the present invention, in the third embodiment, the polymer material is a copolymer of polylactide and carboxylic acid, and a bioactive material is bound to one end thereof. It is characterized in that it is fixed on the intermediate reactor layer by an electrostatic force.

본 발명의 제 6 실시예에 따르면, 본 발명의 생체활성물질 코팅방법은, 과산화수소와 황산을 혼합한 혼산용액, 오존, 플라즈마를 이용해 화학적으로 임프란트의 외주면상에 산화막을 활성화시켜 OH기를 생성하는 활성막형성단계와; 상기 활성막상에 (CH2)N 일단에는 Si-(O-R)3이 그리고 타단에는 아민기, 카르복실기, 알데히이드기로 구성된 그룹으로부터 선택된 하나가 결합된 실란기 또는 (CH2)N일단에는 PO4가 그리고 타단에는 아민기, 카르복실기, 알데히이드기로 구성된 그룹으로부터 선택된 하나가 결합된 인산기로 구성된 그룹으로부터 선택된 하나를 활성막과 반응시켜 중간반응기층을 형성하는 중간반응기층형성단계와; 매트릭스물질과 생체활성물질을 소정한 혼합하여 농도제어를 행하고 중간반응기층상에 도포하여 중간반응기층의 아민기 또는 카르복실기와는 아미드반응을 통해 그리고 알데히드기와는 이민반응을 통해 중간반응기층에 매트릭스물질과 생체활성물질을 고정하는 고정단계를 포함하는 것을 특징으로 한다. According to the sixth embodiment of the present invention, the bioactive material coating method of the present invention is an activity of chemically activating an oxide film on the outer peripheral surface of an implant by using a mixed acid solution, ozone, and plasma mixed with hydrogen peroxide and sulfuric acid to generate OH groups. A film forming step; Si- (OR) 3 on one end of (CH 2 ) N and one selected from the group consisting of an amine group, a carboxyl group, and an aldehyde group on the active layer, or PO 4 on one end of (CH 2 ) N And the other end includes an intermediate reactor layer forming step of forming an intermediate reactor layer by reacting an active membrane with one selected from the group consisting of phosphoric acid groups bound to one selected from the group consisting of an amine group, a carboxyl group, and an aldehyde group; The matrix material and the bioactive material are mixed in a predetermined concentration to control the concentration, and then applied on the intermediate reactor layer. The amine group or carboxyl group in the intermediate reactor layer is subjected to the amide reaction and the imide reaction with the aldehyde group. It characterized in that it comprises a fixing step of fixing the bioactive material.

본 발명의 제 7 실시예에 따르면, 본 발명의 생체활성물질 코팅방법은, 과산화수소와 황산을 혼합한 혼산용액, 오존, 플라즈마를 이용해 화학적으로 임프란트 의 외주면상에 산화막을 활성화시켜 OH기를 생성하는 활성막형성단계와; 상기 활성막상에 (CH2)n일단에는 Si-(O-R)3이 그리고 타단에는 아민기, 카르복실기, 알데히이드기로 구성된 그룹으로부터 선택된 하나가 결합된 실란기 또는 (CH2)n일단에는 PO4가 그리고 타단에는 아민기, 카르복실기, 알데히이드기로 구성된 그룹으로부터 선택된 하나가 결합된 인산기로 구성된 그룹으로부터 선택된 하나를 활성막과 반응시켜 중간반응기층을 형성하는 중간반응기층형성단계와; 폴리락티드와 카르복실산의 공중합 폴리머에 생체활성물질을 결합하고 이를 정전기적 힘에 의해 중간반응기층상에 고정하는 고정단계를 포함하는 것을 특징으로 한다.According to the seventh embodiment of the present invention, the bioactive material coating method of the present invention is an activity of chemically activating an oxide film on the outer circumferential surface of an implant using a mixed acid solution mixed with hydrogen peroxide and sulfuric acid, ozone, and plasma to generate OH groups. A film forming step; Si- (OR) 3 at one end of (CH 2 ) n on the active layer, and a silane group having one selected from the group consisting of an amine group, a carboxyl group, and an aldehyde group at the other end, or PO 4 at one end of (CH 2 ) n And the other end includes an intermediate reactor layer forming step of forming an intermediate reactor layer by reacting an active membrane with one selected from the group consisting of phosphoric acid groups bound to one selected from the group consisting of an amine group, a carboxyl group, and an aldehyde group; And a fixing step of coupling the bioactive material to the copolymer of polylactide and carboxylic acid and fixing the bioactive material on the intermediate reactor layer by electrostatic force.

출원인은 이하에서 첨부도면을 참조하여 앞서 본 실시예들을 상세하게 설명한다. Applicants will now be described in detail with reference to the present embodiments with reference to the accompanying drawings.

도 2는 본 발명의 일실시예에 따른 생체활성물질이 코팅된 치과용 임프란트의 개략 단면도이다. 도 2에 도시된 바에 의하면, 치과용임프란트의(3)의 외주면상에는 활성막(31), 중간반응기층(33), 매트릭스물질(32)과 생체활성물질(34)이 순차적으로 적층되어 있다. 2 is a schematic cross-sectional view of a dental implant coated with a bioactive material according to one embodiment of the present invention. As shown in FIG. 2, the active membrane 31, the intermediate reactor layer 33, the matrix material 32, and the bioactive material 34 are sequentially stacked on the outer circumferential surface of the dental implant 3.

도 4a에 도시된 바와 같이, 상기 활성막(31)은 임프란트의 표면(3)에 오존, 플라즈마 또는 과산화수소와 황산을 적정농도로 혼합한 piranha용액을 이용해 화학적으로 산화막을 활성화시켜 OH기능기(41)를 형성함으로써 생성되며, OH기능기는 후술하는 실란기 또는 인산기와 반응하여 중간반응기층을 형성하게 된다.As shown in FIG. 4A, the active layer 31 chemically activates an oxide layer using a piranha solution in which ozone, plasma, or hydrogen peroxide and sulfuric acid are mixed at an appropriate concentration on the surface 3 of an implant. It is produced by forming a), the OH functional group is reacted with a silane group or a phosphate group to be described later to form an intermediate reactor layer.

도 4b 내지 4c에 도시된 바와 같이, 상기 중간반응기층(33)은 OH기능기를 가 진 활성막(31)상에 실란기(42) 또는 인산기(43)를 반응시켜 실란화 반응 또는 인산화 반응을 통해 형성된다. 상기 실란기(42)는 n=1~18로 연결된 (CH2)n일단에는 Si-(O-R)3이 그리고 타단에는 아민기(NH2)(도 4b), 카르복실기(COOH), 알데히이드기(CHO)로 구성된 그룹으로부터 선택된 하나가 결합되어 있는데, 여기서, R은 -Cl, -CH3, -CH2CH3로 구성된다. 또한, 상기 인산기(43)는 n=1~18인 (CH2)n일단에는 PO4가 그리고 타단에는 아민기(NH2)(도 4b), 카르복실기(COOH), 알데히이드기(CHO)로 구성된 그룹으로부터 선택된 하나가 결합되어 있는 것이다. As shown in FIGS. 4B to 4C, the intermediate reactor layer 33 reacts a silane group 42 or a phosphate group 43 on an active layer 31 having an OH functional group to perform a silanization reaction or a phosphorylation reaction. Is formed through. The silane group 42 is Si- (OR) 3 at one end (CH 2 ) n is connected to n = 1-18 and the amine group (NH 2 ) (Fig. 4b), carboxyl group (COOH), aldehyde at the other end One selected from the group consisting of groups (CHO) is bonded, wherein R is composed of —Cl, —CH 3 , —CH 2 CH 3 . In addition, the phosphoric acid group 43 is PO 4 at one end of (CH 2 ) n having n = 1 to 18 and an amine group (NH 2 ) at the other end (FIG. 4B), a carboxyl group (COOH), and an aldehyde group (CHO). One selected from the group consisting of is combined.

상기 매트릭스물질(45)은 생체활성물질과 유사한 크기를 가지는 단분자 또는 고분자 형태로서 일단에는 아민기(NH2), 카르복실기(COOH)(도 4c), 알데히이드기(CHO)로 구성된 그룹으로부터 선택된 하나가 결합되어 있고 타단에는 생체활성물질과 반응성이 없는 OH기 또는 CH3기가 결합되어 있는 물질이며, 생체활성물질은 조골세포와 결합되어 조골세포의 증식과 분화를 촉진하는 역할을 하며 펩티드, transforming growth factor(TGF)나 Insulin-like growth factor(IGF)나 Bone morphogentic protein(BMP)와 같은 것들을 예를 들 수 있지만, 바람직하게는 펩티드가 적합하다. 도 4d에 도시된 바와 같이, 이들은 모두 중간반응기층(33)의 아민기 또는 카르복실기와는 아미드반응을 통해 그리고 알데히드기와는 이민반응을 통해 중간반응기층에 고정된다. 매트릭스물질은 생체활성물질과 소정의 농도비로 혼합되어 있는데, 생체활성물질사이에 삽입되어 생체활성물질의 공간분포와 배향을 조정하여 생체활성물질의 조골세포(1)와의 결합성을 증대시켜 활성특성을 극대화하는 역할을 한다. The matrix material 45 is in the form of a single molecule or polymer having a size similar to that of a bioactive material, and is formed from a group consisting of an amine group (NH 2 ), a carboxyl group (COOH) (FIG. 4C), and an aldehyde group (CHO). The selected one is bound and the other end is a material that is bound to the OH group or CH 3 group that is not reactive with the bioactive material, the bioactive material is combined with osteoblasts to promote the proliferation and differentiation of osteoblasts, peptides, Examples include transforming growth factor (TGF), insulin-like growth factor (IGF), and bone morphogentic protein (BMP), but peptides are preferred. As shown in FIG. 4D, they are all fixed to the intermediate reactor layer through an amide reaction with an amine group or a carboxyl group of the intermediate reactor layer 33 and through an imine reaction with an aldehyde group. The matrix material is mixed with the bioactive material at a predetermined concentration ratio. The matrix material is interposed between the bioactive materials and adjusts the spatial distribution and orientation of the bioactive materials to increase the binding properties of the bioactive materials to the osteoblasts (1). Plays a role in maximizing

도 5a는 본 발명의 다른 실시예에 따른 생체활성물질이 코팅된 치과용 임프란트에 있어서 도 4c에 도시된 중간반응기층상에 생체활성물질이 결합된 고분자물질을 고정하는 단계를 나타내는 개략도이며, 도 5b는 도 5a에 따른 생체활성물질이 코팅된 치과용 임프란트의 개략도이다. Figure 5a is a schematic diagram showing the step of fixing the bioactive material is bonded polymer material on the intermediate reactor layer shown in Figure 4c in the dental implant coated with the bioactive material according to another embodiment of the present invention, Figure 5b 5 is a schematic view of a dental implant coated with a bioactive material according to FIG. 5A.

본 발명의 다른 실시예에 따르면, 도 5a와 도 5b에 도시된 바와 같이, 중간반응기층(33)이 형성된 뒤에, 일단에는 펩티드와 같은 생체활성물질(54)이 결합된 고분자물질(52) 예컨대 폴리락티드와 카르복실산의 공중합폴리머를 정전기적 힘을 이용해 고정함으로서 생체활성물질을 중간반응기층상에 고정한다. According to another embodiment of the present invention, as shown in FIGS. 5A and 5B, after the intermediate reactor layer 33 is formed, a polymer material 52, for example, to which a bioactive material 54 such as a peptide is bound, is connected at one end. The bioactive material is fixed on the intermediate reactor layer by fixing the copolymer of polylactide and carboxylic acid using electrostatic force.

출원인은 앞서 본 발명의 실시예들을 설명하였지만, 본 발명은 앞서 본 실시예에만 국한되지 아니하고 다양한 변경예와 수정예를 포함하는 것으로 해석되어야 한다. Applicants have described the embodiments of the present invention above, but the present invention should not be construed as limited to the above embodiments but should be construed to include various changes and modifications.

본 발명은 앞서 본 구성에 의하여 다음과 같은 효과를 얻을 수 있다.The present invention can obtain the following effects by the above configuration.

본 발명은, 임프란트의 표면에 형성된 활성막상에 중간반응기층을 적층한 뒤 그 중간반응기층상에 매트릭스물질과 생체활성물질을 고정하거나 생체활성물질이 결합된 고분자물질을 고정함으로써 멸균과정 후에도 생체활성이 그대로 유지되어 유통과 보관이 용이할 뿐만 아니라 치과용임프란트와 생체활성물질간에 충분한 접착력을 확보함으로써 치과용 임프란트 시술시 골유착기간을 단축시킬 수 있는 효과 를 가진다.The present invention, after stacking the intermediate reactor layer on the active membrane formed on the surface of the implant and fixed the matrix material and the bioactive material on the intermediate reactor layer or by fixing the polymer material combined with the bioactive material bioactivity is increased even after sterilization process As it is maintained as it is, it is not only easy to distribute and store, but also secures sufficient adhesive force between the dental implant and the bioactive material, thereby reducing the bone adhesion period during the dental implant procedure.

본 발명은 생체활성물질의 분포밀도나 배향을 조절함으로써 펩티드와 조골세포간의 결합성을 높여 생체활성물질의 활성특성을 극대화할 수 있다는 효과를 도모할 수 있다.The present invention can improve the binding properties between the peptide and osteoblasts by adjusting the distribution density or orientation of the bioactive material can achieve the effect that can maximize the active properties of the bioactive material.

Claims (7)

임프란트의 외주면상에 형성된 활성막상에 생성된 중간반응기층에 매트릭스물질과 생체활성물질을 화학적 공유결합으로 고정하여 형성되며, 상기 생체활성물질은 매트릭스물질과 소정의 농도로 혼합되어 있어 임프란트의 외주면상에서 조골세포와 효율적인 결합이 가능하도록 하는 분포공간과 배향을 가지는 것을 특징으로 하는 치과용 임프란트.Formed by chemical covalent bonding of a matrix material and a bioactive material to an intermediate reactor layer formed on the active film formed on the outer peripheral surface of the implant, the bioactive material is mixed with the matrix material at a predetermined concentration, and thus on the outer peripheral surface of the implant Dental implant, characterized in that it has a distribution space and orientation to enable efficient coupling with osteoblasts. 임프란트의 외주면상에 형성된 활성막상에 생성된 중간반응기층에 생체활성물질이 결합된 고분자물질을 고정하여 형성되며, 상기 생체활성물질은 고분자물질에 의해 조골세포와 효율적인 결합이 가능하도록 하는 분포공간과 배향을 가지는 것을 특징으로 하는 치과용 임프란트.It is formed by fixing a polymer material combined with a bioactive material to the intermediate reactor layer formed on the active membrane formed on the outer peripheral surface of the implant, the bioactive material is a distribution space to enable efficient coupling with osteoblasts by the polymer material; Dental implant, characterized in that it has an orientation. 제 1 항 내지 제 2 항 중 어느 한 항에 있어서, 상기 활성막은 임프란트의 외주면상에 OH기능기를 생성함으로써 형성되며, 상기 중간반응기층은 (CH2)n일단에는 Si-(O-R)3이 그리고 타단에는 아민기, 카르복실기, 알데히이드기로 구성된 그룹으로부터 선택된 하나가 결합된 실란기를 상기 활성막과 실란화 반응을 통해 생성되거나 (CH2)n일단에는 PO4가 그리고 타단에는 아민기, 카르복실기, 알데히이드기로 구성된 그룹으로부터 선택된 하나가 결합된 인산기를 상기 활성막과 인산화 반응을 통해 생성되는 것을 특징으로 하는 치과용 임프란트.The method according to any one of claims 1 to 2, wherein the active layer is formed by generating an OH functional group on the outer circumferential surface of the implant, wherein the intermediate reactor layer is (CH 2 ) n once Si- (OR) 3 and At the other end, a silane group in which one selected from the group consisting of an amine group, a carboxyl group, and an aldehyde group is bonded is formed through a silanization reaction with the active membrane, or (CH 2 ) n at one end is PO 4 and at the other end is an amine group, a carboxyl group, Dental implant, characterized in that the phosphate group is selected from the group consisting of aldehyde group is produced through the phosphorylation reaction with the active membrane. 제 3 항에 있어서, 상기 매트릭스물질은 생체활성물질과 크기가 유사하며 일단에는 활성막의 OH기와 반응성을 가지는 아민기, 카르복실기와 알데히드기로 구성된 그룹으로부터 선택된 하나를 가지며 타단에는 생체활성물질과 반응성이 없는 OH기와 CH3기로 구성된 그룹으로부터 선택된 하나를 가지는 단분자 또는 고분자물질이며, 4. The matrix material of claim 3, wherein the matrix material is similar in size to the bioactive material and has one selected from the group consisting of an amine group, a carboxyl group, and an aldehyde group reactive to the OH group of the active membrane, and the other end is not reactive with the bioactive material. It is a single molecule or a polymer having one selected from the group consisting of OH group and CH 3 group, 상기 매트릭스물질과 생체활성물질은 중간반응기층의 아민기 또는 카르복실기와는 아미드반응을 통해 그리고 알데히드기와는 이민반응을 통해 중간반응기층에 고정되는 것을 특징으로 하는 치과용 임프란트.And the matrix material and the bioactive material are fixed to the intermediate reactor layer through an amide reaction with an amine group or a carboxyl group of the intermediate reactor layer and an imine reaction with an aldehyde group. 제 3 항에 있어서, 상기 고분자물질은 폴리락티드와 카르복실산의 공중합 폴리머로서 그 일단에는 생체활성물질이 결합되어 있어서 정전기적 힘에 의해 중간반응기층상에 고정되는 것을 특징으로 하는 치과용 임프란트.4. The dental implant of claim 3, wherein the polymer material is a copolymer of polylactide and carboxylic acid, and a bioactive material is bonded to one end thereof and fixed to the intermediate reactor layer by an electrostatic force. 과산화수소와 황산을 혼합한 혼산용액, 오존, 플라즈마를 이용해 화학적으로 임프란트의 외주면상에 산화막을 활성화시켜 OH기를 생성하는 활성막형성단계와,An active film forming step of chemically activating an oxide film on the outer circumferential surface of the implant using a mixed acid solution, ozone, and plasma mixed with hydrogen peroxide and sulfuric acid, 상기 활성막상에 (CH2)n일단에는 Si-(O-R)3이 그리고 타단에는 아민기, 카르복실기, 알데히이드기로 구성된 그룹으로부터 선택된 하나가 결합된 실란기 또는 (CH2)n일단에는 PO4가 그리고 타단에는 아민기, 카르복실기, 알데히이드기로 구성된 그룹으로부터 선택된 하나가 결합된 인산기로 구성된 그룹으로부터 선택된 하나를 활성막과 반응시켜 중간반응기층을 형성하는 중간반응기층형성단계와,Si- (OR) 3 at one end of (CH 2 ) n on the active layer, and a silane group having one selected from the group consisting of an amine group, a carboxyl group, and an aldehyde group at the other end, or PO 4 at one end of (CH 2 ) n And at the other end, an intermediate reactor layer forming step of forming an intermediate reactor layer by reacting one selected from the group consisting of phosphoric acid groups bound to one selected from the group consisting of an amine group, a carboxyl group, and an aldehyde group with an active membrane, 매트릭스물질과 생체활성물질을 소정한 혼합하여 농도제어를 행하고 중간반응기층상에 도포하여 중간반응기층의 아민기 또는 카르복실기와는 아미드반응을 통해 그리고 알데히드기와는 이민반응을 통해 중간반응기층에 매트릭스물질과 생체활성물질을 고정하는 고정단계를 포함하는 생체활성물질의 코팅방법. The matrix material and the bioactive material are mixed in a predetermined concentration to control the concentration, and then applied on the intermediate reactor layer. The amine group or carboxyl group in the intermediate reactor layer is subjected to the amide reaction and the imide reaction with the aldehyde group. Coating method of the bioactive material comprising a fixing step of fixing the bioactive material. 과산화수소와 황산을 혼합한 혼산용액, 오존, 플라즈마를 이용해 화학적으로 임프란트의 외주면상에 산화막을 활성화시켜 OH기를 생성하는 활성막형성단계와,An active film forming step of chemically activating an oxide film on the outer circumferential surface of the implant using a mixed acid solution, ozone, and plasma mixed with hydrogen peroxide and sulfuric acid, 상기 활성막상에 (CH2)n일단에는 Si-(O-R)3이 그리고 타단에는 아민기, 카르복실기, 알데히이드기로 구성된 그룹으로부터 선택된 하나가 결합된 실란기 또는 (CH2)n일단에는 PO4가 그리고 타단에는 아민기, 카르복실기, 알데히이드기로 구성된 그룹으로부터 선택된 하나가 결합된 인산기로 구성된 그룹으로부터 선택된 하나를 활성막과 반응시켜 중간반응기층을 형성하는 중간반응기층형성단계와,Si- (OR) 3 at one end of (CH 2 ) n on the active layer, and a silane group having one selected from the group consisting of an amine group, a carboxyl group, and an aldehyde group at the other end, or PO 4 at one end of (CH 2 ) n And at the other end, an intermediate reactor layer forming step of forming an intermediate reactor layer by reacting one selected from the group consisting of phosphoric acid groups bound to one selected from the group consisting of an amine group, a carboxyl group, and an aldehyde group with an active membrane, 폴리락티드와 카르복실산의 공중합 폴리머에 생체활성물질을 결합하고 이를 정전기적 힘에 의해 중간반응기층상에 고정하는 고정단계를 포함하는 것을 특징으로 하는 치과용 임프란트.A dental implant comprising a fixing step of binding a bioactive material to a copolymer of polylactide and carboxylic acid and fixing it on an intermediate reactor layer by electrostatic force.
KR1020050032456A 2005-04-19 2005-04-19 Biomaterial - coated dental implant and the coating method KR20060110190A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100892866B1 (en) * 2008-06-20 2009-04-15 오스템임플란트 주식회사 Fixation method of biological materials on implant surface
WO2018206286A1 (en) * 2017-05-09 2018-11-15 Straumann Holding Ag Process for providing a dental article

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100892866B1 (en) * 2008-06-20 2009-04-15 오스템임플란트 주식회사 Fixation method of biological materials on implant surface
WO2018206286A1 (en) * 2017-05-09 2018-11-15 Straumann Holding Ag Process for providing a dental article
US11638631B2 (en) 2017-05-09 2023-05-02 Straumann Holding Ag Process for providing a dental article

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