WO2017176090A1 - 생체활성글라스를 포함하는 지르코니아 임플란트 및 이의 제조 방법 - Google Patents

생체활성글라스를 포함하는 지르코니아 임플란트 및 이의 제조 방법 Download PDF

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WO2017176090A1
WO2017176090A1 PCT/KR2017/003829 KR2017003829W WO2017176090A1 WO 2017176090 A1 WO2017176090 A1 WO 2017176090A1 KR 2017003829 W KR2017003829 W KR 2017003829W WO 2017176090 A1 WO2017176090 A1 WO 2017176090A1
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WIPO (PCT)
Prior art keywords
oxide
bioactive glass
zirconia
implant
coating layer
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PCT/KR2017/003829
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English (en)
French (fr)
Inventor
박상원
오계정
이경구
이도재
김지원
장경준
Original Assignee
전남대학교산학협력단
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Priority claimed from KR1020160043371A external-priority patent/KR101826967B1/ko
Priority claimed from KR1020170044424A external-priority patent/KR101951343B1/ko
Application filed by 전남대학교산학협력단 filed Critical 전남대학교산학협력단
Publication of WO2017176090A1 publication Critical patent/WO2017176090A1/ko

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    • 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
    • A61L27/30—Inorganic 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
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • A61L27/32—Phosphorus-containing materials, e.g. apatite
    • 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

Definitions

  • a zirconia implant comprising bioactive glass and a method of making the same
  • the present invention relates to leuconia implants and methods for making them containing bioactive glass.
  • Implant which means transplant, is a defect in living tissue
  • Double teeth also known as third teeth, are implants used here and are suitable for the body through additional surgery, such as bone grafts and bone reconstructions, on the jaw bone of the site where the tooth is missing or where the tooth is pulled out. It is used in dental treatments that plant and detox the function of natural teeth.
  • the implant should be superior in the characteristics of osseointegmentation, which is a morphological, physiological, and direct connection with the jawbone, in which normal function is maintained.
  • Many methods have been proposed to lower the failure rate and increase the fixation with the bone. For example, it is common practice to mechanically secure the bone to the bone by designing the implant in a spiral design.However, the fixation force of the bone by mechanical fixation is not comparable to that of the natural tooth, so that the implant and the bone can be further improved. There is a lot of research going on.
  • Physical methods include forming roughness on the surface of the implant. Grinding, spraying (sandblasting, etc.), acid etching, etc. Specifically, sandblasting is performed by using alumina having a small particle size. Etching is a method of etching the surface using acid solution. It is mainly used with sandblasting because acid etching alone does not show the surface treatment effect.
  • Implants with increased surface roughness by these physical methods can achieve better mechanical binding and strength by providing a greater contact and fixation area between the implant and bone tissue.
  • the uniqueness of teeth is important, but it is a tooth that is directly visible in appearance, and therefore plays a very important role in social aspects. In the case of anterior teeth, it is indistinguishable from the natural teeth that are visible from the teeth. Aesthetic traits are more demanding. In addition, the probability of damage to a transposition due to physical stratification is higher than that of Tachia, so the implants are significantly more likely to be replaced by implants. Therefore, the implants are physically, chemically and biocompatible. Physicochemical and chemical properties are also important, but there is also a need for aesthetic qualities that do not differ from actual teeth and the naked eye.
  • No. 2011-0041682 discloses a method for producing a zirconia tooth, which is formed from zirconia, which is colored with a colorant similar to natural colors.
  • Zirconia has excellent strength, biocompatibility, and no corrosion, so it does not cause any inflammation reactions or allergies when used in humans. It is also widely used as an implant material to replace metals with its excellent mechanical properties.
  • Zirconia however, has a coating layer formed on its surface, unlike ordinary metals.
  • Korean Patent No. 10-1430748 discloses a bioactive chromosome glass containing silicon oxide, aluminum oxide, sodium oxide, magnesium oxide, barium oxide, calcium oxide, titanium oxide, and niobium oxide to solve the above problem. Tooth prostheses containing the bioactive chromoglass are known. When zirconia is applied to the bioactive chromoglass, it is known that the surface roughness is slightly formed to improve the fixing force and binding force with bone tissue. However, there is still a disadvantage of poor biocompatibility.
  • the treatment process is subject to a number of constraints:
  • the process of forming the surface roughness required for the zirconia formed on the surface of the coating layer can result in physical and chemically strong laminar spacing. Defects at the waco-layer,
  • An object of the present invention is to provide an zirconia-based implant and a method for manufacturing the same, which can improve excellent zirconia properties such as biocompatibility, corrosion resistance, excellent mechanical properties, and low bacterial deposition rate.
  • Bioactive glass layer to be coated wherein the bioactive glass layer is
  • the rough surface is formed on the surface of the bioactive glass layer.
  • An implant according to an embodiment of the present invention may further include a bioinorganic coating layer coated on the bioactive glass layer, wherein the bioinorganic coating layer is
  • bioinorganic coating layer may include bioactive glass, bioceramic, or may contain bioactive glass and bioceramic together. have.
  • the surface of the bioactive glass layer may have a roughness of 0.5 to 5.0.
  • the method for producing an implant of the present invention is directed to a) on a material comprising zirconia.
  • a method for manufacturing an implant according to an embodiment of the present invention includes the steps of: c) forming a bioinorganic coating layer comprising at least one selected from bioactive glass and bioceramic on a bioactive glass layer having a surface roughness formed thereon. May contain more.
  • a method for manufacturing an implant according to an embodiment of the present invention comprises the steps of first sintering a bioactive glass layer between step a) and step b) and second sintering of a biological inorganic coating layer after step c). May contain more steps
  • the first sintering may be performed at 1,200 to 00 o C.
  • the second sintering can be performed at 800 ⁇ l, 200 ° C.
  • the bioinorganic coating layer may include bioactive glass, bioceramic, or bioactive glass and bioceramic together.
  • the surface roughness of step b) is 0.5 to 5.0.
  • Unevenness with an average size may be formed.
  • the bioactive glass includes silicon oxide, aluminum oxide, sodium oxide,
  • the bioactive glass may contain any one or more selected from magnesium oxide, barium oxide, calcium oxide, titanium oxide and niobium oxide, etc.
  • the bioactive glass may also be selected from iron oxide, phosphorus pentoxide, boron oxide, potassium oxide and strontium oxide. It can contain one or more.
  • the bioceramic is composed of hydroxide apatite (Ca l0 (PO 4 ) 6 (OH) 2 , HA),
  • Phosphorus pentoxide P 2 0 5
  • a third calcium phosphate Ca 3 (P0 4) 2 , TCP
  • octa-calcium phosphate Ca s 3 ⁇ 4 (P0 4) 6.5H 2 0, OCP
  • octa-calcium phosphate Ca 4 It can contain any one or more of 0 (P0 4 ) 2 , 4CP).
  • Implant Zirconia of the present invention can be used as a base material to prevent adverse effects of biocompatibility deteriorated by coating and surface treatment of bioactive glass, bioceramic and the like, thereby promoting bone formation, biocompatibility, and low bacteria.
  • the deposition rate has an excellent effect.
  • the mechanical properties such as durability, corrosion resistance, and fracture resistance are remarkably improved, and the same color as natural teeth can be realized.
  • the implant of the present invention can be applied to various medical fields,
  • FIG. 5 shows the results obtained by measuring the thermal expansion coefficient of the bioactive glass layer in Preparation Example 2.
  • the zirconia implant and its manufacturing method are described in detail.
  • an implant refers to an artificial material that is implanted in a human body.
  • an artificial material including an artificial valve, an artificial joint, an artificial tooth, an intraocular lens, etc., has a wide range of implants. Means.
  • the present invention is directed to a material comprising zirconia; and a coating on the material
  • the present invention relates to an implant including a bioactive glass layer, wherein a roughness is formed on a surface of the bioactive glass layer.
  • It may further comprise a bioinorganic coating layer comprising bioactive glass and / or bioceramic coated on the bioactive glass layer.
  • the implant of the present invention has a single or multi-layer structure on zirconia material.
  • the coating layer is formed and the surface roughness is formed on one or more coating layers of each coating layer, the mechanical and biocompatibility characteristics are very excellent.
  • the surface roughness is formed.
  • Various side effects such as mechanical degradation and biocompatibility can be prevented due to peeling of the coating layer.
  • zirconia In general, zirconia is known to have excellent biocompatibility because it does not cause inflammatory reactions or allergic reactions. However, due to the above side effects, the range of treatment is not wide. There are conventional limitations that are not easy to handle.
  • the present inventors have studied the composition and sequence of each step of the implant manufacturing method in various angles.
  • the present invention has excellent surface roughness even though the zirconia has a single or multi-layered coating layer, and thus high biocompatibility.
  • Branch Provided are implants and methods of making the same.
  • the method for producing an implant of the present invention is directed to a) on a material comprising zirconia.
  • the method may further include forming a bioinorganic coating layer on the glass layer including any one or both selected from bioactive glass and bioceramic.
  • Step a) is a process of adding the characteristics of the bioactive glass at the same time, which is an essential process for forming the surface roughness of step b). If the surface roughness is directly formed on the zirconia material, the surface roughness is formed. Zirconia may be subjected to strong stress and heat, leading to a decrease in the durability of the sturdy column. Therefore, the zirconia material should be subjected to the bioactive glass layering process in step a) before the surface roughening process in step b).
  • the material on which the coating layer is formed may be zirconia-based or zirconia-based metals containing heterogeneous elements.
  • the specific properties such as thickness, weight, density, and shape of the material depend on the target location of the implant. It is not limited because it can be processed and adjusted appropriately for the purpose.
  • the material can be manufactured in the following way: Zirconia powder can be introduced into a molding press and press molded to produce zirconia substrates for implants. The pressure exerted at this time may be appropriately adjusted according to the urine constituent density, for example 50-300 MPa.
  • the method for manufacturing an implant according to an embodiment of the present invention may further include presintering the material containing zirconia before step a). If further comprising the step of presintering, the durability of the zirconia material As this improves,
  • the mechanical properties of the zirconia material can be further prevented by performing the multi-step process such as the bioactive glazing process, the surface roughness forming step b) and the bioinorganic coating layer forming step c).
  • the interfacial adhesion, compactness, and cohesion of the interlayers improve the overall mechanical properties of the implant.
  • the sintering of the pre-sintering step is not limited as long as the above-mentioned effect can be realized, for example, 800 ⁇ l.
  • a temperature of 700 ° C., preferably 1,000 to 1,700 ° C., is preferable in terms of maximizing the above effect.
  • the bioactive glass is used to improve biocompatibility, and to suppress the occurrence of various side effects such as degradation of the mechanical properties of the implant and degradation of biocompatibility due to peeling of the coating layer during the surface roughness forming step b). do.
  • the bioactive glass may be a glass-based compound having excellent biocompatibility, and specifically, silicon oxide (Si0 2 ), aluminum oxide (A1 2 0,), sodium oxide (N 0).
  • It may contain any one or more components selected from magnesium oxide (MgO), barium oxide (BaO), calcium oxide (CaO), titanium oxide (Ti0 2 ) and niobium oxide (Nb 2 0 5 ).
  • MgO magnesium oxide
  • BaO barium oxide
  • CaO calcium oxide
  • Ti0 2 titanium oxide
  • Nb 2 0 5 niobium oxide
  • the bioactive glass is silicon oxide, aluminum oxide and
  • the biocompatible glass may contain 50-80% by weight of silicon oxide, 5-40% by weight of aluminum oxide, and 2-30% by weight of sodium oxide.
  • the aesthetic properties such as transparency, gloss, mechanical properties such as abrasion resistance, layer resistance, and durability, and chemical stability can be further improved.
  • the density of glass is reduced, glass transition degree, softening temperature, etc. As the characteristics of viscosity, etc. improve, the surface of zirconia
  • the bioactive glass layer can be more tightly formed and can reduce the difference in thermal expansion rate between the zirconia material and the bioactive glass layer.
  • the bioactive glass may include silicon oxide, aluminum oxide, sodium oxide, magnesium oxide, barium oxide, calcium oxide, titanium oxide and niobium oxide.
  • silicon oxide 60 to 75 weight %, Aluminum oxide 8 ⁇ 8 weight ⁇ 3 ⁇ 4, sodium oxide 4-10 wt% magnesium oxide 0.1-5 wt% barium oxide 0.1-5 wt ⁇ 3 ⁇ 4, calcium oxide 0.1-5 wt%, titanium oxide 0.1-5 wt% and niobium oxide It can contain 0.1 to 5% by weight. If this is satisfied, even though a large number of coating layers are formed on the material and are formed between the processes, the bonding strength between the layers is maximized, and the mechanical properties such as wear resistance, friction resistance, and durability of the implant are manufactured.
  • the physical properties, chemical resistance, and water resistance of the chemicals can be significantly improved, and they can be adjusted to reflect a wider range of visible light wavelengths to have a color very similar to biological tissues.
  • the crystallization of the glass can be attributed to its excellent crystallization and minimizes the adverse effects of mechanical degradation caused by excessive phase changes in zirconia at each stage.
  • the bioactive glass includes iron oxide, phosphorus pentoxide, boron oxide, potassium oxide and
  • One or more additional ingredients selected from strontium oxide, etc. may be further included. If this is satisfied, transparency may be improved, glass crystallization may be improved, and mechanical properties of the steel can be improved, and thermal expansion rate of zirconia material may be improved. In addition, the solubility of the bioactive glass in the manufacturing process increases and the melting temperature decreases, thereby improving meltability, thereby improving biocompatibility.
  • Bioactive glass can have the appropriate brightness to prevent the glass from breaking It is effective to produce a stronger implant on the physical layer, as well as to control the color of the implant more freely by adjusting the components such as iron oxide and its content.
  • the bioactive glass further contains the additional components. , 0.01-5% by weight of the additional component, specifically 0.1 3% by weight, more specifically 0.1 1% by weight relative to the total weight of the bioactive glass. If this is satisfied, the above effects can be improved.
  • the thermal expansion coefficient of the bioactive glass are not necessarily is severely limited, it is preferred the more the coefficient of thermal expansion of the zirconia material similar, specific, and in a preferred embodiment, the thermal expansion coefficient of the bioactive glass 6.5 ⁇ 12.5 ⁇ ⁇ 6 days, It can provide strong adhesion with zirconia in step a) and the first sintering step described later, and can show good resistance to refractive-induced damage.
  • the sharp composition and the composition ratio of the bioactive glass may be independently applied to the bioactive glass of step a) and the bioactive glass of step c), respectively.
  • the biologically active glass may include each of the components in particulate form.
  • each component may be ground by a milling process to produce bioactive glass.
  • the average particle size of the bioactive glass may be coated, for example, the average particle diameter may be 0.1 to 50 mm 3.
  • each component is wet mixed and pulverized with solvent such as water or alcohol to make bioactive glass.
  • solvent such as water or alcohol
  • the mixed and ground powder slurries can be dried, for example, for 0.5 to 12 hours at 60 to 120 o C.
  • the powder slurries are then calcined at l, 200 to 17,00 o C and converted into molten state.
  • Bioactive glass can be prepared by quenching the quench (10) into glass (Galss).
  • step a) The coating method of step a) is not particularly limited. Dip coating,
  • Aerosol deposition Spin coating, Doctor blade, Dry dipping, Hydro thermal reaction, Sol-gel method, Spray method Or ion beam deposition.
  • deep coating include immersing a zirconia material in a mixture of a solvent and bioactive glass in a column to the zirconia surface.
  • a bioactive glass layer can be formed, wherein the mixing ratio of the bioactive glass and the solvent is as long as the bioactive glass can be coated on the zirconia material by dipping, for example, 1 to 500 wt.
  • zirconia material by dipping, for example, 1 to 500 wt.
  • bioactive glass layer can be formed, this invention is not limited.
  • the average thickness of the bioactive glass layer coated on the zirconia material in step a) is not limited so long as the above-described effect is realized, and may be, for example, 5 to 120 / im.
  • the first sintering step may be further performed.
  • the method for producing an implant of the present invention may be performed between steps a) and b).
  • the first step of sintering the active glass layer may be further included.
  • the biocompatibility is enhanced by the bioactive glass layer, and then the surface roughness formation process in step b) can suppress the occurrence of various side effects of mechanical degradation and biocompatibility degradation due to peeling of the coating layer.
  • the sintering temperature is not limited as long as the above-described effects can be realized, and for example, 700 to l, 700 o C, specifically l, 200 to l, 700 o C, can maximize the effect. Good in terms of
  • step b) by coating the bioactive glass on the zirconia material, it is possible to form the surface roughness of step b) without deteriorating the mechanical properties of the zirconia material.
  • the surface roughness is first formed on the zirconia material, The physicochemical properties of zirconia materials are deteriorated by direct physical / chemical stratification or thermal shock to zirconia materials.
  • Step b) is performed on the surface of the bioactive glass layer coated on the material in step a).
  • Surface roughness is a method of forming irregularities on the surface of a material, such as a mechanical etching method and a chemical etching method, and a variety of methods can be used, but the production of implants having high bending strength can be achieved.
  • the mechanical etching method is preferable in this regard, but this is only a preferable example, but the present invention is not limited thereto.
  • a method of sand blasting may be exemplified by a mechanical etching method.
  • Sand blasting is a method of forming a roughness on a material surface by spraying metal particles or sand particles such as alumina with a strong pressure on the material surface. .
  • the average particle diameter of the particles used for sandblasting is preferably 75 to 250; «n.
  • various variables may be caused by the strength of the injection pressure, which is preferable. It can be 0.1 to 6 MPa.
  • the injection time can be adjusted according to the degree of roughness to be formed, for example, 15 to 45 seconds. However, since the range of the above values is described as a preferable example, the present invention Of course, it is not limited.
  • An example of a chemical etching method is a method of forming an unevenness by contacting an acid solution to a surface of a material. Specifically, the material is brought into contact with an acid solution containing hydrofluoric acid (HF). The surface can be etched to form irregularities due to acid corrosion on the surface of the material. When using hydrofluoric acid solution, 10 to 20% of hydrofluoric acid is used. Aqueous solutions may be used. Contact time is not limited because it can be adjusted to the required average size of unevenness, but can be, for example, 10 to 60 minutes. Contact temperature is not such that a thermal stratification is applied to the material. This may be, for example, 30 to 90 ° C. However, this is only an example and is not intended to limit the invention.
  • the surface roughness can be formed by using the plasma method.
  • the surface roughness forming method using the plasma method can control plasma density with RF power and etch energy by controlling ion energy with lower power to achieve high uniformity.
  • the surface roughness of step b) is 0.5-5.0 / i, preferably 1.0-2.0 / an.
  • the surface roughness in the above range is formed, it is possible to avoid the problem that the strength is excessively reduced.Afterwards, it is effective even after further sintering and forming the biological coating layer. Surface roughness can be maintained, resulting in improved adhesion to the bones of the implant.
  • the implant of the present invention has excellent biocompatibility as it is manufactured, including a) forming a bioactive glass layer and b) forming a surface roughness, but in step a)
  • the layered zirconia-material may be relatively less biocompatible than the pure zirconia material without the coating layer formed.
  • the bioinorganic coating layer of step c) further improves biocompatibility and bone formation.
  • Biocompatibility can be significantly increased, and fracture resistance is significantly increased, which in turn can produce more surface roughness without deteriorating the mechanical properties of the durability, even though the process of forming surface roughness can be performed again as needed. .
  • Step c) is performed on the bioactive glass layer on which the surface roughness of step b) is formed.
  • bioceramic means biocompatible inorganic compounds, specifically, apatite hydroxide (Ca, 0 (PO 4 ) 6 (OH) 2 , HA), phosphorus pentoxide (P 2 0 5 ), 3
  • apatite hydroxide Ca, 0 (PO 4 ) 6 (OH) 2 , HA
  • phosphorus pentoxide P 2 0 5
  • 3 Choose from calcium phosphate (Ca 3 (P0 4 ) 2 , TCP), calcium octaphosphate (Ca s H 2 (P0 4 ) 6.5H 2 0, OCP) and calcium octaphosphate (3 ⁇ 40 ( ⁇ 0 4 ) 2 , 4CP) It may be any one or more than two components.
  • the bio-inorganic coating layer includes bioceramic in step c
  • the biocompatibility deterioration phenomenon may be prevented by step a).
  • the biocompatibility and low bacterial deposition rate are improved
  • Mechanical properties such as fracture resistance can also be improved.
  • the physical and chemical forces applied to the zirconia material in step b) are strongly applied, even if a side effect occurs in which mechanical properties such as structural stability and strength of the zirconia occur, in step c)
  • the bioinorganic coating layer contains bioceramic, the occurrence of the side effect can be suppressed. Therefore, by minimizing the characteristics lost in the steps a) and b) , the overall characteristics can be improved.
  • the bioinorganic coating layer may include bioactive glass and bioceramic, specifically, bioactive glass I.
  • the above-mentioned effects by the bioactive glass can be improved.
  • the interlayer bonding force and biocompatibility can be improved in comparison with the bioinorganic coating layer containing no bioactive glass.
  • the aesthetic properties may be better as the color expression by bioactive glass is improved.
  • the average thickness of the bioinorganic coating layer is not limited so long as the above effects can be realized, and may be, for example, 0.05 to 120 / a. If this is satisfied, the surface roughness formed in step b) may be It is possible to avoid the problems caused by the coating and to minimize the problem of degradation due to the thinness of the layer, which is insignificant or the layer itself is easily broken. However, this is only described as a preferred example. This is not a limitation.
  • the coating method of step c) includes dip coating, aerosol deposition (AD), spin coating, doctor blade, dry dipping, and hydrothermal. (Hydro thermal) reaction, Sol-gel method, spray method or ion beam deposition method can be exemplified. Dip coating is preferred in terms of excellent process efficiency.
  • the present invention is only an example, but the present invention is not limited thereto, and the layer can be formed by a variety of known coating methods.
  • step c) the bioactive glass and / or bioceramic
  • the bioinorganic coating layer is placed on the bioactive glass layer having the surface roughness formed in step b).
  • a method of coating a mixture of bioactive glass particles and / or bioceramic particles in a solvent on the bioactive glass layer in step c) may be exemplified.
  • Glass, bioceramics and solvents that do not react can be exemplified, and solvents such as ⁇ may be exemplified by water, ethanol and the like.
  • the solvent may be 1 to 500 parts by weight based on 1 part by weight of the bioactive glass or the bioceramic.
  • the average particle diameter is 0.5 to 5
  • the particle size range may be 0.1 to 10. If this is to be met, bioactive glass and / or bioceramic
  • the adhesion, bonding force and durability with the bioinorganic coating layer zirconia material can be improved.
  • the step of sintering the biological inorganic coating layer after step c) may further include the step of sintering after the step c), whereby the biological inorganic coating layer is adhered and bonded onto the bioactive glass layer.
  • the zirconia and bioactive glass layers are sintered again, thereby improving the structural stability and mechanical strength of the implant.
  • the sintering temperature is sufficient to achieve the above-mentioned effects. For example, 500-1,200 ° C, specifically 800-1,200 ° C, is desirable in terms of maximizing the above effect.
  • step c The method for manufacturing an implant according to an embodiment of the present invention may be performed in step c).
  • the method may further include forming a surface roughness on the bioinorganic coating layer.
  • Implants that have gone through stage c) may have more surface roughness, as the mechanical properties are very good.
  • the surface roughness may be reduced as a result of the formation of a bioinorganic coating layer, but may further go through the stage of forming the surface roughness.
  • the bond strength with the human body can be further improved without degrading the durability or strength of the implant.
  • the implant of the present invention includes a material containing zirconia; and a bioactive glass layer coated on the material, wherein a roughness is formed on the surface of the bioactive glass layer.
  • the implant may further comprise a bioinorganic coating layer coated on the bioactive glass layer on which the surface roughness is formed.
  • the surface of the bioactive glass layer may have a roughness of 5 to 5.0.
  • the bioinorganic coating layer may include any one or two selected from bioceramic and bioactive glass.
  • the bioactive glass is as described in the method for producing the implant.
  • the average surface roughness of the pre-sintered zirconia was 0.025 / ffli, hardness was 12.34 GPa, flexural strength was 425 MPa.
  • the Cytotoxic test was also tested on the presintered zirconia, and the results are shown in Table 1 below.
  • a bioactive glass layer was formed and first sintered.
  • the weight percent was mixed by milling at 500 rpm for 50 minutes, pulverized, and then melted at 1,450 ° C. using a firing furnace. After quenching with water, the glass was quenched by water quenching. After the dried glass was thoroughly dried, the glass particles were blown at 500 rpm for 50 minutes to obtain L5 phosphorus particles to prepare SiO r Al 2 O 3 -Na 2 O based bioactive glass powder.
  • the pre-sintered zirconia of Preparation Example 1 was immersed in a mixed solution of 100 parts by weight of distilled water with respect to 1 part by weight of the bioactive glass powder and the bioactive glass powder.
  • the zirconia coated with the bioactive glass powder was then fired.
  • the first sintering at 1,450 ° C to prepare a zirconia formed a bioactive glass layer.
  • the thermal expansion coefficient of the bioactive glass layer is 10.12xlO 6 / ° C as shown in FIG.
  • the zirconia was very close to the 10.65xlO 6 / o C coefficient of thermal expansion.
  • the surface roughness was formed by using the sand blasting method on the surface of the bioactive glass layer of zirconia in which the bioactive glass layer of Preparation Example 2 was formed.
  • alumina particles having an average particle diameter of 90 were sprayed at a pressure of 3.5 MPa for 30 seconds to form a roughness on the surface.
  • the tip of the nozzle to which the alumina particles were sprayed and the bioactive glass layer were sprayed.
  • the linear distance to the surface is 10 mm
  • the surface roughness of the roughened zirconia was 1.25
  • the hardness was 10.60 GPa
  • the flexural strength was 650 MPa.
  • the cytotoxic test was also performed on the zirconia formed with the bioactive glass layer. The results are shown in Table 1 below.
  • the surface roughness was formed on the surface of the bioactive glass layer of zirconia in which the bioactive glass layer of Preparation Example 2 was formed by using an acid etching method.
  • zirconia in which the bioactive glass layer of Preparation Example 2 was formed, was immersed in 15 wt% aqueous hydrofluoric acid (HF) solution at 55 0 C for 30 minutes to etch the surface of the zirconia to form a roughness on the surface. It was.
  • HF hydrofluoric acid
  • the surface roughness of the roughened zirconia was 1.35, the hardness was 12.00 GPa, the flexural strength was 600 MPa. Cytotoxic test was also performed on the zirconia formed with the bioactive glass layer. The results are shown in Table 1 below.
  • the immersion method was used to form and second sinter the bioinorganic coating layer comprising hydroxide apatite and bioactive glass.
  • the average particle diameter is 2;
  • a mixed powder comprising a hydrophobic apatite powder having a particle size ranging from 0.1 to 10 / ⁇ and a Si0 2 -Al 2 0 3 -Na 2 0 based biologically active glass powder of Preparation Example 2 in a ratio of 15: 1 by weight, and an increase of the mixed powder 1
  • the second sintering at 1,000 ° C. bio-inorganic coating layer Molded zirconia was prepared.
  • the average surface roughness of the zirconia on which the bioinorganic coating layer is formed is 2.89.
  • a zirconia with a bio-inorganic coating layer was prepared in the same manner as in Example 3 except that the zirconia with roughness of Example 1 was used instead of the zirconia with roughness of Example 1.
  • the average surface roughness of the zirconia on which the bioinorganic coating layer was formed was 2.46.
  • the flexural strength was 405 MPa.
  • the Cytotoxic test was performed on the zirconia on which the biological inorganic coating layer was formed, and the results are shown in Table 1 below.
  • Example 1 The pre-sintered Example 1 of Preparation Example 1 instead of the zirconia having the roughness of Example 1 Except for the use of zirconia, a zirconia having a bioinorganic coating layer was prepared in the same manner as in Example 3.
  • the flexural strength referred to in the present invention refers to the strength that a material can withstand when pressure is applied.
  • the flexural strengths in manufacturing examples, comparative examples and examples are measured according to the international standard ISO 6872.
  • the cytotoxicity test may be prepared in each preparation, comparative example or example.
  • the specimens were measured in the following manner. Three specimens from each group were placed in a 24 well plate, and then the osteoblasts MC3T3-E1 (ATCC Catalog No. CRL-2593) were dispensed at a density of 5xl0 5 cells / cm 2 into the wells containing the specimens. Incubated at 37 ° C., 5% carbon dioxide incubator for 24 hours.
  • the cells was determined by 1 well Ding, 20 by using the EZ-Cytox (Itsbio, Korea) were cultured, followed by cell to 37 ° C, 5% was in the carbon dioxide incubator banung for 1 h 96 well plate in 100 After dispensing bubbles, the absorbance of each well was measured at 450 nm using a Microtplate (ELISA) reader (ELx 800UV®, Bio-Tek Instrument. Inc., USA). After cell culture,
  • the specimens were fixed for scanning electron microscopy and washed twice with PBS for 10 minutes each, followed by 100% ethanol at 40%, 50%, 60%, 70%, 80% and 90% ethanol, 15 minutes apart. Esau dehydrated three times at 10-minute intervals. The specimens were then dried in a 37 0 C, 5% carbon dioxide incubator and platinum coated for 1 min using ion sputter (EX-200®, Hitachi horiba, Japan).
  • bioinorganic coating layer is further formed after the surface roughness is formed in Example 3
  • the flexural strength was increased in comparison with Example 1, but the flexural strength was reduced in comparison with Example 2.-Therefore, the acid etching in terms of manufacturing an implant having a superior flexural strength was achieved. It is desirable to form surface roughness by sandblasting rather than by sandblasting.
  • Example 1 to 4 cracks did not occur on the surface.
  • Example 3 and Example 4 it was confirmed that the surface irregularities appear as it is compared with Example 1 and Example 2. This is judged to be due to the improved adhesion and bonding properties of the zirconia material and each layer.
  • the coated composite implant has excellent structural stability, that is, the surface roughness is maintained even though the bioinorganic coating layer is further formed on the active glass layer having the surface roughness, and the structural stability is maintained by maintaining the high fracture resistance. You can see that.
  • the biological inorganic coating layer is formed.
  • the convex-convexity is introduced into the surface of the bioactive glass layer, it is judged to be due to the introduction of various structural convexities of cracks, dots, potentials, boundaries, cracks, folds, and corrugations.
  • FIGS. 1, 2, 3, and 4 were prepared in order of Preparation Example 1, Preparation Example 2, Example 1, and Example, respectively.
  • the results of the cell adhesion test in which the degree of cell adhesion according to Example 2 was observed using a scanning electron microscope are shown. Specifically, the result is 24 hours after attaching the cells to the final manufactured zirconia in each manufacturing example or example.
  • the cell adhesion test resulted in the lower cell rather than the manufacturing example 1 (FIG. 1) in which the bioactive glass layer was formed (FIG. 2).
  • Table 1 shows the results of biocompatibility testing the cytotoxic test for the case of Preparation Example 1, Preparation Example 2, Example 1 to Example 4.
  • Example 5 and Examples were used to include only hydroxyapatite and not bioactive glass as the bioinorganic coating layer.
  • the characteristics of flexural strength, cell adhesion, and biocompatibility were inferior as compared with Example 3 and Example 4, respectively.

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Abstract

본 발명은 지르코니아를 베이스 재료로 하는 임플란트에 관한 것으로, 생체활성글라스, 생체세라믹 등의 다중 코팅 처리 및 표면 식각 처리 등이 복합적으로 수행됨에 따라, 생체 적합성이 저하되는 역효과를 방지할 수 있고, 이에 따라 골 형성 촉진, 생체 적합성,낮은 세균 침착률 등이 우수한 효과가 있다. 또한 지르코니아 및 코팅층 간의 결합력이 보다 향상됨에 따라 내구성, 내부식성, 파절 저항성 등의 기계적 물성이 현저히 향상되는 효과가 있을 뿐만 아니라, 그럼에도 자연 치아와 동일한 색상이 구현되는 효과가 있다.

Description

명세서
발명의명칭:생체활성글라스를포함하는지르코니아임플란트및 이의제조방법
기술분야
[1] 본발명은생체활성글라스를포함하는지르코니아임플란트및이의제조 방법에관한것이다.
배경기술
[2] 임플란트 (Implant)는이식 (移植)을의미하는것으로,생체조직의결손을
보완하기위해,인공재료혹은천연재료를결손부에이식하여형태의 재건， 기능을대행시킬때에사용되는것으로서，예컨대인공밸브，인공관절，인공 치아，안내렌즈둥이있다.
[3] 이중인공치아는제 3의치아라고도하며，여기에사용되는임플란트로서， 치아의 결손이 있는부위나치아가뽑힌자리의턱뼈에골이식，골신장술등의 부가적인수술을통하여생체적합한임플란트본체를심어자연치의기능을 희복시켜주는치과치료법에사용된다.
[4] 따라서 임플란트는정상적인기능이유지되고있는턱뼈와의형태적，생리적， 직접적결합인골유착 (osseointegmtion)둥의특성이우수하여야한다.이에따라 여러종류임플란트가개발되었으며，생체에 적용하는치과용임플란트시슬의 실패율을낮추고뼈와의고정력을높이기위한많은방법들이제시되었다. 예컨대임플란트를나선형으로디자인함으로써뼈에기계적으로강하게 고정시키는방법이 일반적으로사용되고있다.그러나기계적고정에의한 뼈와의고정력은자연치아에비교될수준이아니기 때문에 임플란트와뼈와의 접합을더욱향상시키기위한많은연구가진행되고있다.
[5] 이에따라，임플란트와뼈와의고정력및결합력을보다향상시키기위해
다양한방법이제시되었으며，이는상술한기계적고정을포함하는물리적 방법과화학적 방법등으로구분될수있다.
[6] 물리적방법에는임플란트의표면에거칠기를형성시키는방법이 있으며， 그라인딩，분사법 (샌드블라스팅등),산식각등이 있다.구체적으로, 샌드블라스팅 (Sandblasting)은작은입경의 알루미나를사용하여상변이에의한 강화를유도하는방법이디-.산식각 (Etching)은산용액을이용하여표면을 식각하는방법으로,산식각만으로는표면처리효과가잘나타나지않아 샌드블라스팅과함께주로사용되는방법이다.
[7] 이러한물리적방법으로표면거칠기가증가된임플란트는임풀란트와뼈조직 사이에더큰접촉및고착영역을부여함으로써더 양호한기계적구속력과 강도를얻을수있다.
[8] 화학적 방법에는임플란트표면의화학적특성을변경하는것이 있으며, 예컨대뼈조직의재생을자극하기위하여임플란트표면에뼈와유사한무기물 성분인인산칼슘등을코팅하는방법등이 있다.이러한처리방법은생체적 합성을유도하여뼈와의물리적인고정력및결합력뿐만아니라화학적인생체 적합성또한향상시킬수있다.
[9] 임플란트는물리적특성,화학적특성，생체적합성특성등의물리 /화학적 고유물성외에，최근에는심미적특성까지도요구되고있다.예컨대
전치 (앞니)의경우에는치아고유의특성도중요하지만，외관상직접적으로 드러나는치아이므로사회적인측면에서도매우중요한역할을한다.전치의 경우，치아의고유성능보다도외관상보여지는자연치아와구별되지않을 정도의심미성특성이더요구되고있는것이현실이다.또한전치는물리적인 층격에의해손상될확률도타치아에비해높음에따라임플란트로대체될 확률도상당히높다.따라서임플란트는물리적특성,화학적특성,생체적합성 특성둥의물리 /화학적고유물성도중요하지만,실제치아와육안으로차이나지 않올정도의심미성특성또한요구되고있다.
[10] 임플란트의심미성특성의요구가증대됨에따리-,한국공개특허
제 2011-0041682호에는인공치아전체를자연의 색상과유사한착색액으로 착색한지르코니아로성형하는지르코니아치이-의제조방법이개시되어 있다.
[11] 지르코니아는강도와생체적합성이우수하고부식이없기 때문에인체에사용 시어떠한염증반웅이나알레르기도유발하지않는다.또한뛰어난기계적 성질올바탕으로금속을대체하는임플란트재료로널리사용되고있다.
최근에는크라운브릿지의코어뿐만아니라임플란트영역에서도적용되고 있는데，높은생체적합성과탁월한기계적물성,낮은세균침착률은치과 재료로서높은평가를받고있다.
[12] 그러나코팅층이표면에형성된지르코니아는일반적인금속과는달리
분사법이나산식각방법을통한표면거칠기형성이어려운한계가있다. 따라서코팅층이표면에형성된지르코니아에산식각이나분사법둥을이용한 표면처리를하더라도접착강도가떨어지는단점이있다.이는
지르코니아로부터표면코팅층의박리 (Delamination)현상에기인하며， 기본적으로지르코니아와코팅층의 열팽창계수가서로유사하지않거나 냉각속도가지나치게빠를경우둥에의해발생한다.
[13] 한국둥록특허제 10- 1430748호에는상기문제를해결하기위하여산화규소, 산화알루미늄，산화나트륨,산화마그네습，산화바륨,산화칼슘,산화티타늄및 산화니오븀을포함하는생체활성색조글라스및상기생체활성색조글라스를 포함하는치아용보철물에대하여공지되어있다.생체활성색조글라스를 지르코니아에코팅할경우,표면거칠기가다소형성되어뼈조직과의고정력, 결합력등이향상되는효과가있는것으로알려져 있으나,여전히 생체적합성이 떨어지는단점이 있다.
[14] 또한지르코니아의많은장점에도불구하고，결합력，고정력둥올향상시키기 위한처리공정에는많은제약이따른다.코팅층이표면에형성된지르코니아에 요구되는표면거칠기를형성하는과정에서는지르코니아에물리적, 화학적으로강한층격이유발될수있다.이러한층격에의해지르코니아와 코팅층의낮은결합력,지르코니아와코팅층계면에서의결함,
지르코니아-코팅층의 열팽창계수의부조화등의지르코니아와코팅층간의 문제가발생할수있으며，지르코니아의휨등의지르코니아자체의 기계적물성 또한크게저하될수있다.또한경우에따라생체적합성이오히려저하되는 경우도발생할수있다.
[15] 따라서인체의 일부를대체하는임플란트가상기대체대상과동일하거나그 이상의특성과역할올갖도록하기위해많은비용과시간이투자되어 연구되고 있으나,아직까지상기 인체대체대상의성능과는견즐정도가되지못하는 것이사실이다.
발명의상세한설명
기술적과제
[16] 본발명의목적은지르코니아자체의 생체적합성，내부식성，우수한기계적 특성，낮은세균침착률등의우수한특성이향상될수있는지르코니아를 재료로하는임플란트및이의 제조방법을제공하는것이다.
과제해결수단
[17] 본발명의임플란트는지르코니아를포함하는재료;및상기재료상에
코팅되는생체활성글라스층;을포함하며，상기생체활성글라스층은
생체활성글라스를포함하며 ,상기 생체활성글라스층의표면에거칠기가형성된 것이다.
[18] 본발명의 일예에따른임플란트는상기 생체활성글라스층상에코팅되는 생체무기코팅층을더포함할수있으며,상기 생체무기코팅층은
생체활성글라스및생체세라믹중에서선택되는어느하나또는들을포함할수 있다.즉,상기생체무기코팅층은생체활성글라스를포함할수있거나, 생체세라믹을포함할수있거나,생체활성글라스와생체세라믹을함께포함할 수있다.
[19] 본발명의일예에있어서,상기생체활성글라스층의표면은 0.5~5.0 의 거칠기가형성된것일수있다ᅳ
[20] 본발명의임플란트의제조방법은 a)지르코니아를포함하는재료상에
생체활성글라스를코팅하여생체활성글라스층을형성하는단계및 b)상기 생체활성글라스층상에표면거칠기를형성하는단계를포함한다.
[21] 본발명의일예에따른임플란트의제조방법은 c)표면거칠기가형성된 생체활성글라스층상에생체활성글라스및생체세라믹중에서선택되는어느 하나또는둘이상을포함하는생체무기코팅층을형성하는단계를더포함할수 있다. [22] 본발명의일예에따른임플란트의제조방법은상기 a)단계와상기 b)단계 사이에생체활성글라스층을제 1소결하는단계및상기 c)단계이후에 생체무기코팅층을제 2소결하는단계를더포함할수있다ᅳ
[23] 본발명의 일예에 있어서,상기제 1소결은 1 ,200~ 00oC에서수행될수있다.
[24] 본발명의일예에있어서,상기제 2소결은 800~l,200oC에서수행될수있다.
[25] 본발명의일예에있어서,상기 생체무기코팅층은생체활성글라스를포함할 수있거나，생체세라믹을포함할수있거나，생체활성글라스와생체세라믹을 함께포함할수있다.
[26] 본발명의일예에있어서,상기 b)단계의표면거칠기는 0.5~5.0 의
평균크기를가지는요철이형성되는것일수있다.
[27] 본발명에서생체활성글라스는산화규소,산화알루미늄，산화나트륨，
산화마그네슘，산화바륨,산화칼슘，산화티타늄및산화니오븀등에서선택되는 어느하나또는둘이상을포함할수있다.또한상기생체활성글라스는산화철, 오산화인，산화붕소，산화칼륨및산화스트론튬등에서선택되는어느하나또는 둘이상을더포함할수있다.
[28] 본발명에서생체세라믹은수산화아파타이트 (Cal0(PO4)6(OH)2, HA),
오산화인 (P205),제 3인산칼슘 (Ca3(P04)2, TCP),옥타인산칼슘 (Cas¾(P04)6.5H20, OCP)및옥타인산칼슘 (Ca40(P04)2, 4CP)둥에서선택되는어느하나또는둘 이상을포함할수있다.
발명의효과
[29] 본발명의임플란트는지르코니아를베이스재료로서 ,생체활성글라스， 생체세라믹등의코팅처리，표면처리등에의해생체적합성이 저하되는 역효과를방지할수있으며,이에따라골형성촉진,생체적합성 ,낮은세균 침착률등이우수한효과가있다.
[30] 또한본발명의 임플란트는지르코니아및코팅층간의결합력이보다
향싱 -됨에따라내구성,내부식성,파절저항성등의기계적물성이현저히 향상되는효과가있으며,그럼에도자연치아와동일한색상이구현되는효과가 있다.
[31] 따라서본발명의 임플란트는다양한의료분야에적용이가능하고그
웅용범위가넓은이점이 있다.
[32] .여기에명시적으로언급되지않은효과라하더라도，본발명의기술적특징에 의해기대되는이하의명세서에서기재된효과및그잠정적인효과는본발명의 명세서에기재된것과같이취급됨을첨언한다.
도면의간단한설명
[33] 도 1내지도 4는각각제조예 1，제조예 2，실시예 1및실시예 2에따른경우의 세포부착정도를주사전자현미경을이용하여관측한결과를나타낸
것이다. (세포부착이후 24시간이지난시점에서 100배율로관측) [34] 도 5는제조예 2에서의생체활성글라스층의 열팽창계수를측정하여그결과를 나타낸것이다.
발명의실시를위한형태
[35] 이하첨부한도면들올참조하여본발명의생체활성글라스를포함하는
지르코니아임플란트및이의제조방법올상세히설명한다.
[36] 본발명에기재되어 있는도면은당업자에게본발명의사상이층분히전달될 수있도록하기위해 예로서제공되는것이디 ·.따라서본발명은제시되는 도면들에한정되지않고다른형태로구체화될수도있으며，상기도면들은본 발명의사상을명확히하기위해과장되어도시될수있다.
[37] 또한본발명에서사용되는기술용어및과학용어에 있어서다른정의가 없다면,이발명이속하는기슬분야에서통상의 지식을가진자가통상적으로 이해하고있는의미를가지며，하기의설명및 첨부도면에서본발명의요지를 불필요하게흐릴수있는공지기능및구성에대한설명은생략한다.
[38] 또한본발명에서특별한언급없이불분명하게사용된 %의단위는중량 %를 의미한다.
[39] 또한본발명에서언급되는 "임플란트"는인체에 이식 (移植)되는인공재료를 의미하는것으로,예컨대인공밸브，인공관절,인공치아，안내 렌즈등을 포함하는인공재료로서 넓은범위의 임플란트를의미한다.
[40]
[41] 본발명은지르코니아를포함하는재료;및상기 재료상에코팅되는
생체활성글라스층;을포함하며,상기 생체활성굴라스층의표면에거칠기가 형성된임플란트에 관한것이다.또한본발명의 제 2의 양태로，상기
생체활성글라스층상에코팅되는생체활성글라스및 /또는생체세라믹을 포함하는생체무기코팅층을더포함할수있다.
[42] 특히본발명의 임플란트는지르코니아재료상에한층또는다층구조의
코팅층이형성되고,각코팅층중하나이상의코팅층에표면거칠기까지 형성됨에따라기계적물성및생체적합성특성이매우우수하다.뿐만아니라 본발명의 임플란트의제조방법으로임플란트를제조할경우，표면거칠기형성 과정에서코팅층의박리등으로인한기계적물성저하,생체적합성저하등의 다양한부작용을방지할수있다.
[43] 일반적으로,지르코니아는염증반웅이나알레르기를유발하지않아생체 적합성이우수한것으로알려져 있음에도，상기부작용등때문에그웅용 범위는넓지않으며，지르코니아자체의특성에기인하여다른금속과같은코팅 처리,표면처리가수월하지않은종래의한계가있다.
[44] 하지만본발명자는임플란트제조방법의각단계의구성 ,순서둥을다각도로 연구한결과,본발명은지르코니아에 한층또는다층구조의코팅층이 형성됨에도우수한표면거칠기를가지며，그럼에도높은생체적합성을가지는 임플란트및이의제조방법을제공한다.
[45]
[46] 본발명의임플란트의제조방법은 a)지르코니아를포함하는재료상에
생체활성글라스를코팅하여 생체활성글라스층을형성하는단계및 b)상기 생체활성글라스층상에표면거칠기를형성하는단계를포함한다.또한상기 제조방법은 b)단계이후 c)표면거칠기가형성된생체활성글라스층상에 생체활성글라스및생체세라믹증에서선택되는어느하나또는둘을포함하는 생체무기코팅층을형성하는단계를더포함할수있다.
[47] 상기 a)단계는이후의 b)단계의표면거칠기형성을위한필수과정인동시에 생체활성글라스의특성을부가하는과정이다.지르코니아재료에표면 거칠기를직접형성할경우,표면거칠기형성과정에서지르코니아에강한웅력 및열이가해져강도둥의내구성 저하를초래할수있다.따라서지르코니아 재료는 b)단계의표면거칠기형성과정 전에 a)단계의생체활성글라스층형성 과정이먼저선행되어야한다.
[48] 상기 a)단계의 재료는지르코니아 (산화지르코늄)를포함하는임플란트용
소재를의미하고，코팅층이형성되는기재를의미하며，지르코니아또는 이종원소를함유하는지르코니아계금속일수있다.상기재료의두께，중량, 밀도，모양등의구체적특성은임플란트의사용대상위치에따라요구목적에 맞게적절히가공,조절될수있으므로제한되지않는다.구체적인일예로,상기 재료는다음과같은방법으로제조될수있다.지르코니아분말을성형용 프레스에투입하고,가압성형하여 임플란트용지르코니아기재를제조할수 있다.이때가해지는압력은요구성형밀도에따라적절히조절될수있으며, 예컨대 50-300 MPa일수있다.하지만이는일예일뿐,본발명이 이에제한되지 않으며，공지된다양한문헌을통해제조될수있다.
[49] 본발명의 일예에따른임플란트의제조방법은 a)단계이전에,지르코니아를 포함하는재료를예비소결하는단계를더포함할수있다.예비소결하는단계를 더포함할경우,지르코니아재료의내구성이향상됨에따라 a)단계의
생체활성글라스코팅과정, b)단계의표면거칠기형성과정， c)단계의 생체무기코팅층형성과정등의다단계공정이수행됨에따른지르코니아 재료의기계적물성저하를더욱방지할수있다.또한지르코니아재료와긱- 층간의계면간밀착성，치밀성,결합력둥이향상되어임플란트의 전체기계적 물성이향상되는효과가있다.상기 예비소결하는단계의소결은도는상술한 효과가구현될수있을정도라면제한되지않으며，예컨대 800~l,700oC, 바람직하게는 1,000~1,700°C인것이상기효과를극대화할수있는측면에서 좋다.
[5이 상기 생체활성글라스는생체적합성올더향상시키고，이후 b)단계의표면 거칠기형성과정에서코팅층의박리둥으로인한임플란트의기계적물성저하, 생체적합성 저하등의다양한부작용의발생올억제하기위해사용된다. [51] 상기 생체활성글라스는생체적합성이우수한글라스계화합물일수있으며， 구체적으로,산화규소 (Si02),산화알루미늄 (A120,),산화나트륨 (N 0).
산화마그네슘 (MgO),산화바륨 (BaO),산화칼슘 (CaO),산화티타늄 (Ti02)및 산화니오븀 (Nb205)둥에서선택되는어느하나또는둘이상의성분을포함할수 있다.이러한생체활성글라스가지르코니아재료상에코팅되거나,표면 거칠기가형성된생체활성글라스층상에코팅됨으로써 ,생체적합성특성의 향상은물론，심미적특성，내화학성특성과함께파절저항성,강도,내마모성 둥의기계적물성이보다향상될수있다.
[52] 바람직한일예로，상기생체활성글라스는산화규소,산화알루미늄및
산화나트륨을포함할수있다.구체적으로,상기 생체화성글라스는산화규소 ᅳ 50-80중량 %，산화알루미늄 5~40중량 %및산화나트튬 2~30중량 %를포함할수 있다.이를만족할경우，생체적합성특성의향상은물론,투명성，광택등의 심미적특성，내마모성,내층격성,내구성등의기계적물성，화학적안정성등이 보다향상될수있다.또한글라스의밀도가보다감소되고,유리전이은도, 연화온도，점도등의특성이향상됨에따라，지르코니아표면에
생체활성글라스층이보다견고히밀착형성될수있으며,지르코니아재료와 생체활성글라스층의열팽창율의차이를보다감소시킬수있다.
[53] 보다바람직한일예로，상기생체활성글라스는산화규소,산화알루미늄, 산화나트륨，산화마그네슘,산화바륨，산화칼슘，산화티타늄및산화니오븀올 포함할수있다.구체적으로，산화규소 60~75중량 %,산화알루미늄 8ᅳ 8중량 <¾, 산화나트륨 4~10증량 산화마그네슘 0.1~5중량 산화바륨 0.1-5증량 <¾, 산화칼슘 0.1~5중량 %,산화티타늄 0.1~5중량 %및산화니오븀 0.1~5중량 %를 포함할수있다.이를만족할경우,재료상에다수의코팅층을형성하고그과정 사이에거칠기까지형성됨에도,각층간의 결합력이극대화되어제조되는 임플란트의내마모성,내마찰성,내구성등의기계적물성과내화학성，내수성 둥의화학적물성이현저히향상될수있다.또한생체조직과매우유사한색을 갖도록보다넓은범위의가시광선파장을반사하도록조절할수있다.이는 생체활성글라스의제조과정에서글라스의 결정화가우수한것에기인할수 있으며，각단계에서지르코니아의과도한상변화에따른기계적물성 저하등의 부작용발생을최소화할수있다.
[54] 상기 생체활성글라스는산화철,오산화인，산화붕소,산화칼륨및
산화스트론튬등에서선택되는어느하나또는둘이상의추가성분을더포함할 수있다.이를만족하는경우,투명성이보다향상될수있고，글라스결정화를 향상시켜강도둥의기계적물성이보다향상될수있으며,지르코니아재료의 열팽창율에보다근접할수있다.또한제조과정에서생체활성글라스의 용해도가증가되고연화온도가감소하여용융성이향상됨으로써,생체 적합성이보다향상될수있는효과가있다.또한제조과정에서
생체활성글라스가적당한휘도를가질수있어글라스의파절을방지하여 물리적층격에보다강한임플란트를제조할수있는효과가있다.뿐만아니라 산화철등의성분및이의함량을조절함으로써임플란트의색상을보다 자유롭게조절할수있다.상기 생체활성글라스가상기추가성분을더포함할 경우에,생체활성글라스전체중량에대하여상기추가성분 0.01-5중량 %, 구체적으로 0.1 3중량 %，보다구체적으로 0.1 1중량 %를더포함할수있다. 이를만족하는경우，상기효과들이보다향상될수있다.
[55] 상기 생체활성글라스의열팽창계수는크게제한되는것은아니며，지르코니아 재료의열팽창계수가유사할수록바람직하다.구체적이며바람직한일예로， 생체활성글라스의열팽창계수가 6.5~12.5χΐσ6일경우, a)단계및후술하는 제 1소결단계에서지르코니아와의강한접착성을제공할수있으며,굴절 -유도 손상에좋은저항성을보일수있다.
[56] 상기 생체활성글라스의상슬한조성및조성비는 a)단계의생체활성글라스및 c)단계의 생체활성글라스에각각독립적으로적용될수있다.
[57] 상기생체활성글라스는상기각성분들이 입자상으로포함될수있으며，
예컨대각성분들을블밀링공정으로분쇄하여 생체활성글라스를제조할수 있다.구체적으로,생체활성글라스의평균입경은코팅될수있을정도라면 무방하며,예컨대평균입경이 0.1~50卿인것일수있다ᅳ바람직하게는
평균입경이 0.5-5卿이고,입도범위가 0.1~10 /«η인것일수있다.이때각 성분들이물또는알코을둥과같은용매와함께습식흔합및분쇄되어 생체활성글라스가제조될수있다.습식혼합및분쇄된분말슬러리는예컨대 60~120oC에서 0.5~12시간동안건조될수있다.이후，상기분말슬러리는 l,200~17,00oC에서소성되어용융물상태로상변환되며，상기용융물을 프¾(1 0화되어글라스 (Galss)화되도록급넁 (Quenching)시켜 생체활성글라스를 제조할수있다.
[58] 상기 a)단계의코팅방법은크게제한되지 않으며 ,딥코팅 (Dip coating),
에어로졸데포지션 (Aerosol deposition, AD),스핀코팅 (Spin coating),닥터 블레이드 (Doctor blade),건식디핑 (Dry dipping),수열 (Hydro thermal)반웅, 졸겔 (Sol-gel)법,스프레이법 (Spray)또는이온빔증착법 (Ion beam deposition)등이 예시될수있다.딥코팅의구체적인일예로,물둥의용매와생체활성글라스를 흔합한흔합물에지르코니아재료를침지하여지르코니아표면에
생체활성글라스층을형성할수있다.이때생체활성글라스와용매의혼합비는 생체활성글라스가침지에의해지르코니아재료상에코팅될수있을정도면 무방하며，예컨대생체활성글라스 1중량부에대하여용매 1~500중량부일수 있다.하지만이외에다양한방법으로지르코니아재료상에
생체활성글라스층을형성할수있으므로，이에본발명이제한되는것은아니다.
[59] 이렇게상기 a)단계에서지르코니아재료상에코팅된생체활성글라스층의 평균두께는상술한효과가구현될정도라면크게제한되지않으며,예컨대 5~120 /im일수있다. [60] 상기 a)단계에서지르코니아재료상에생체활성글라스층올형성한이후에 제 1소결하는단계가더수행될수있다.즉,본발명의임플란트의제조방법은 a) 단계와 b)단계사이에생체활성글라스층올제 1소결하는단계를더포함할수 있다.상기 a)단계이후소결하는단계까지수행됨으로써,지르코니아재료상에 생체활성글라스층이기계적물성및계면간결합력 (밀착성，치밀성둥)이현저히 향상된다.따라서생체활성글라스층에의해생체적합성이더향상되고，이후 b) 단계의표면거칠기형성과정을거침으로써，코팅층의박리등으로인한기계적 물성저하,생체 적합성저하둥의다양한부작용의발생을억제할수있는 효과가있다.상기소결온도는상술한효과가구현될수있을정도라면 제한되지않으며，예컨대 700~l,700oC,구체적으로 l,200~l,700oC인것이상기 효과를극대화할수있는측면에서좋다.
[61] 상술한바와같이,지르코니아재료상에 생체활성글라스를코팅함으로써, 지르코니아재료의 기계적물성 저하없이 이후 b)단계의표면거칠기 형성을 가능하게한다.예컨대지르코니아재료상에먼저표면거칠기를형성할경우, 지르코니아재료에직접적으로물리적 /화학적층격또는열충격이가해짐에 따라지르코니아재료의 기계적물성저하를가져온다.
[62] 상기 b)단계는 a)단계에서 재료상에코팅된생체활성글라스층상에표면
거칠기를형성하는과정이다.표면거칠기형성방법은재료표면에요철을 형성시킬수있는방법,예컨대기계적식각방법，화학적식각방법등이 있으며, 다양한방법들을혼용할수있으나,높은굴곡강도를가지는임플란트의제조를 위한측면에서 기계적식각방법이바람직하다.하지만이는바람직한일예일 뿐,본발명이 이에제한되지않음은물론이다.
[63] 바람직한일예로，기계적식각방법으로샌드블라스팅등의방법이 예시될수 있다.샌드블라스팅은알루미나등의금속입자또는모래입자를재료표면에 강한압력으로분사시킴으로써재료표면에거칠기를형성하는방법이다.
이러한방법은본기술분야에서 널리공지되어있으므로，다양한선행문헌을 참고하여사용할수있다.구체적인일예로,작은평균입경의입자를사용할 경우,상변이에의한강화를유도할수있으나，큰평균입경의입자를사용할 경우,홈집이커져강도가지나치게 저하될수있다.따라서샌드블라스팅에 사용되는입자의평균입경은 75~250 ;«n인것이바람직하다.또한분사압력의 세기에의해서도다양한변수가유발될수있으므로,바람직하게는 0.1~6 MPa일 수있다.분사시간은형성되는거칠기 정도에 따라적당히조절할수있으며， 예컨대 15~45초일수있다.하지만상술한값의범위는바람직한일예로서 설명된것이므로,이에본발명이제한되지않음은물론이다.
[64] 화학적식각방법의 예로는재료표면에산용액을접촉시켜요철을형성하는 방법을들수있다.구체적으로，불산 (Hydrofluoric acid, HF)등올포함하는 산용액에상기 재료를접촉시켜 재료의표면을에칭시켜，재료표면에산부식에 의한요철을형성시킬수있다.불산수용액을사용하는경우， 10~20%의불산을 포함하는수용액이사용될수있다.접촉시간은요구되는평균크기의요철이 형성될수있을정도로조절될수있으므로제한되지않으나,예컨대 10~60분일 수있다.접촉온도는재료에열층격이가해질정도가아닌수준이면무방하며， 예컨대 30~90°C일수있다.하지만이는바람직한일예로서설명한것일뿐， 이에본발명이제한되는것은아니다.
[65] 이외에도플라즈마법을이용하여표면거칠기를형성할수있다.구체적인일 예로,플라즈마법을이용한표면거칠기형성방법은 RF전력으로플라즈마 밀도를제어하고,하부전력으로이온에너지를제어하여식각함으로써높은 균일도의표면거칠기를형성할수있다.이때플라즈마식각속도，선택도， 균일한반웅성은반웅기체의종류,반웅기형태， ;공정조건등의다양한변수에 의해영향을받을수있으며 ,공지된비특허문헌 [l](Valverde, Guilherme B., et al. "Surface characterisation and bonding of Y-TZP following non-thermal plasma treatment." Journal of dentistry 41.1 (2013): 51-59.), [2](dos Santos, Daniela
Micheline, et al. "Aging effect of atmospheric air on lithium disilicate ceramic after nonthermal plasma treatment." The Journal of prosthetic dentistry 115.6 (2016):
780-78그)들을참고할수있다.
[66ᅵ 상기 b)단계의표면거칠기는 0.5-5.0 / i,바람직하게는 1.0-2.0 /an의
평균크기를가지는요철이형성되는것일수있다.위범위의표면거칠기가 형성될경우,강도가지나치게저하되는문제를방지할수있다.또한이후,소결, 생체무기코팅층둥을형성하는과정이더수행됨에도유효표면거칠기를 유지할수있어,임플란트의뼈에 대한부착성향상을도모할수있다.
[67] 상술한바와같이 ,본발명의임플란트는생체활성글라스층을형성하는 a) 단계및표면거칠기를형성하는 b)단계를포함하여제조됨에따라생체 적합성이우수하지만， a)단계에서생체활성글라스층이형성된지르코니이- 재료는코팅층이형성되지않은순수지르코니아재료와비교하여상대적으로 생체적합성이낮을수있다ᅳ그러나이후 c)단계의생체무기코팅층을더 코팅함으로써,생체친화성과골형성촉진둥의 생체적합성을현저히증가시킬 수있다.또한파절저항성이현저히증가되며,이에따라이후필요에따라표면 거칠기를형성하는과정이재차수행될수있음에도내구성둥의기계적물성의 저하없이표면거칠기를더형성할수있는효과가있다.
[68] 상기 c)단계는 b)단계의표면거칠기가형성된생체활성글라스층상에
생체활성글라스및생체세라믹중에서선택되는어느하나또는둘을포함하는 생체무기코팅층을형성하는과정이다.이때상기 생체활성글라스는앞서 서술한 a)단계의생체활성글라스로서설명한바와같다.
[69] 본발명에서생체세라믹은생체적합한무기화합물을의미하며 ,구체적으로， 수산화아파타이트 (Ca,0(PO4)6(OH)2, HA),오산화인 (P205),제 3인산칼슘 (Ca3(P04)2, TCP),옥타인산칼슘 (CasH2(P04)6.5H20, OCP)및옥타인산칼슘 ( ¾0(Ρ04)2, 4CP) 둥에서선택되는어느하나또는둘이상의성분을포함하는것일수있다. [70] 특히상기 c)단계에서 생체무기코팅층이 생체세라믹을포함할경우,상기 a) 단계에의한생체적합성 저하현상을방지할수있다.또한생체적합성 ,낮은 세균침착률등의특성이향상됨에도,파절저항성등의기계적특성또한 향상될수있다.구체적으로，상기 b)단계에서 지르코니아재료에 인가되는 물리적,화학적힘이강하게작용됨에따라지르코니아의구조안정성,강도 등의기계적특성의 저하되는부작용이발생하더라도 c)단계에서
생체무기코팅층이생체세라믹을포함할경우,상기부작용발생을억제할수 있다ᅳ따라서 a)단계, b)단계에서손실되는특성을최소화함으로써,전반적인 특성모두를향상시킬수있는효과가있다.
[71 ] 뿐만아니라,요철이형성된이후에생체세라믹을포함하는생체무기코팅층이 형성됨에도，미세한구조적요철 (점,전위,입계，크랙，접힘,주름등의형상)이 코팅층에의해덮이거나막히는현상없이실질적으로유지되는현저한효과가 있다.따라서생체적합성특성이향상되는것은물론，표면거칠기가유지되어 뼈조직등과의고정력,결합력특성또한우수한효과가있다ᅳ
[72] 바람직한일예로,상기 생체무기코팅층은생체활성글라스및생체세라믹을 포함할수있으며,구체적으로,생체활성글라스 I.중량부에대하여생체세라믹
5~300중량부，구체적으로 5~100중량부，보다구체적으로 5~30중량부，보다 더욱구체적으로 5~15증량부를포함할수있다.이를만족할경우,
생체활성글라스에의한상술한효과들이향상될수있다.생체세라믹과 생체활성글라스를포함하는생체무기코팅층일경우,생체활성글라스를 포함하지않는생체무기코팅층과비교하여층간결합력과생체적합성이보다 향상될수있다.또한생체활성글라스에의한색표현이보다향상됨에따라 심미적특성이더욱우수할수있다.
[73] 상기 생체무기코팅층의평균두께는상술한효과들이구현될수있을정도라면 제한되지않으며,예컨대 0.05~120 /a일수있다.이를만족하는경우, b) 단계에서형성된표면거칠기가생체무기코팅층의코팅에의해감소되는 문제를방지할수있고,층의두께가너무얇아상기 효과들이미미하거나층 자체가쉽게깨져손실되는내구성저하문제를최소화할수있다.하지만이는 바람직한일 예로서설명된것일뿐,본발명이이에제한되는것은아니다.
[74] 상기 c)단계의코팅방법은딥코팅 (Dip coating),에어로졸데포지션 (Aerosol deposition, AD),스핀코팅 (Spin coating),닥터블레이드 (Doctor blade),건식 디핑 (Dry dipping),수열 (Hydro thermal)반웅,졸겔 (Sol-gel)법,스프레이법 (Spray) 또는이온빔증착법 (Ion beam deposition)둥이 예시될수있다.바람직하게는 공정효율이우수한측면에서딥코팅이좋다.하지만이는바람직한일예일뿐, 본발명이 이에제한되는것은아니며,공지된다양한코팅방법으로층을 형성할수있다.
[75] 상기 c)단계에서생체활성글라스및 /또는생체세라믹을포함하는
생체무기코팅층을 b)단계의표면거칠기가형성된생체활성글라스층상에 형성할경우,상기 c)단계로생체활성글라스입자및 /또는생체세라믹입자를 용매에분산시킨흔합물을상기 생체활성글라스층상에코팅하는방법이 예시될수있다.이때상기용매는지르코니아재료，생체활성글라스, 생체세라믹둥과반웅하지않는용매라면무방하며 , ρΗ가증성인용매,예컨대 물,에탄올등이 예시될수있다.용매의사용함량은생체활성글라스， 생체세라믹이상기 생체세라믹층상에코팅될수있올정도면무방하며，예컨대 생체활성글라스또는생체세라믹 1증량부에대하여용매 1~500중량부일수 있다.
[76] 상기 생체활성글라스또는상기생체세라믹의평균입경및입도범위는코팅될 수있을정도라면무방하며,예컨대평균입경이 0.1~50卿인것일수있다.
바람직하게는평균입경이 0.5~5 이고，입도범위가 0.1~10 인것일수있다. 이를만족할경우,생체활성글라스및 /또는생체세라믹을포함하는
생체무기코팅층이지르코니아재료와의밀착력,결합력 및내구성이향상될수 있다.
[77] 상기 c)단계이후에생체무기코팅층올제 2소결하는단계를더포함할수있다ᅳ 이렇게 c)단계이후소결하는단계까지수행됨으로써,생체무기코팅층이 생체활성글라스층상에밀착및결합되며층의기계적물성이향상된다.이와 함께지르코니아재료，생체활성글라스층도재차소결되므로,임플란트의구조 안정성 및기계적강도가보다향상되는효과가있다.상기소결온도는상술한 효과가구현될수있올정도면무방하며,예컨대 500~l,200oC,구체적으로 800~1,200°C인것이상기효과를극대화할수있는측면에서바람직하다.
[78] 본발명의일예에따른임플란트의제조방법은경우에따라상기 c)단계
이후에생체무기코팅층상에표면거칠기를형성하는단계를더포함할수있다. c)단계까지거친임플란트는기계적물성이 매우우수함에따라표면거칠기를 더형성할수있다.생체무기코팅층이형성됨에따라표면거칠기가감소될 여지가있을수있으나,표면거칠기를형성하는단계를더거칠수있음에따라 임플란트의내구성，강도등의기계적물성의저하없이도인체 (뼈)와의 결합력을더욱향상시킬수있다.
[79] 상술한바와같이,본발명의임플란트는지르코니아를포함하는재료;및상기 재료상에코팅되는생체활성글라스층;을포함하며，상기생체활성글라스층의 표면에거칠기가형성된것이다.또한본발명의 임플란트는상기표면거칠기가 형성된생체활성글라스층상에코팅되는생체무기코팅층을더포함할수있다. 또한상기 생체활성글라스층의표면은으5~5.0 의거칠기가형성된것일수 있다.상기생체무기코팅층은생체세라믹및생체활성글라스중에서선택되는 어느하나또는둘을포함할수있다.이때상기 생체세라믹및상기
생체활성글라스는상기 임플란트의제조방법에서서술한것과같다.
[80]
[81] 이하본발명을제조예,실시예를통해상세히설명하나，이들은본발명을보다 상세하게설명하기위한것으로，본발명의권리범위가하기의실시예에의해 한정되는것은아니다.
[82]
[83] [제조예 1]
[84] 직경이 19 mm이고높이가 1.4 mm인디스크형태의지르코니아 (Zr02)기재를 소성로를이용하여 l,040oC에서 예비소결하였디-.예비소결된지르코니아의평균 표면거칠기는 0.025 /ffli이었고，경도는 12.34 GPa이었으며，굴곡강도는 425 MPa이었다.또한상기 예비소결된지르코니아에대해세포독성시험 (Cytotoxic test)을테스트하였으며,그결과는하기표 1에도시되어 있다.
[85] [제조예 2]
[86] 제조예 1의 예비소결된지르코니아표면에하기와같은방법으로
생체활성글라스층을형성하고제 1소결하였다.
[87] 구체적으로, Si02분말 70중량 %, A1203분말 20중량 %및 Na20분말 10
중량 %를 50분동안 500 rpm으로볼밀링하여흔합하고분쇄한후에 ,소성로를 이용하여 1,450°C에서용융 (Melting)시켰다.용융후냉각수를이용하여 급냉 (Water quenching)시켜글라스결정화과정을거쳤다.결정화된글라스를 층분히건조시킨후, 50분동안 500 rpm으로평균입경이 L5 인입자가되도록 블밀링하여 SiOrAl203-Na20계생체활성글라스분말을제조하였다.
[88] 그리고상기생체활성글라스분말과생체활성글라스분말 1중량부에대하여 증류수 100중량부를혼합한혼합액에제조예 1의 예비소결된지르코니아를 침지하였다.이어서생체활성글라스분말이도포된지르코니아를소성로를 이용하여 1,450°C에서제 1소결하여 생체활성글라스층이형성된지르코니아를 제조하였다.
[89] 상기 생체활성글라스층의열팽창계수는도 5에서와같이 10.12xlO6/°C
정도이었으며,이는지르코니아의열팽창계수인 10.65xlO6/oC와매우근접한 것임을알수있다.
[90] 상기 생체활성글라스층이형성된지르코니아의평균표면거칠기는 0.55 im이었고，경도는 6.23 GPa이었으며 ,굴곡강도는 850 MPa이었다.또한상기 생체활성글라스층이형성된지르코니아에대해세포독성시험 (Cytotoxic test)을 테스트하였으며,그결과는하기표 1에도시되어 있다.
[91] [실시예 1]
[92] 제조예 2의생체활성글라스층이형성된지르코니아의 생체활성글라스층 표면에샌드블라스팅방법올이용하여표면거칠기를형성하였다.
[93] 구체적으로，제조예 2의 생체활성글라스층이형성된지르코니아의
생체활성글라스층표면에 ,평균입경이 90 인알루미나입자를 3.5 MPa의 압력으로 30초동안분사시켜，상기표면에거칠기를형성시켰다.이때 알루미나입자가분사되는노즐의끝부분과상기생체활성글라스층표면과의 직선상거리가 10 mm가되도록하였으며， [94] 상기거칠기가형성된지르코니아의평균표면거칠기는 1.25 이었고，경도는 10.60 GPa이었으며,굴곡강도는 650 MPa이었다.또한상기생체활성글라스층이 형성된지르코니아에대해세포독성시험 (Cytotoxic test)을테스트하였으며 ,그 결과는하기표 1에도시되어있다.
[95] [실시예 2]
[96] 제조예 2의생체활성글라스층이형성된지르코니아의 생체활성글라스층 표면에산식각방법을이용하여표면거칠기를형성하였다.
[97] 구체적으로， 15중량 %의불산 (HF)수용액에제조예 2의생체활성글라스층이 형성된지르코니아를 550C에서 30분동안침지하여상기지르코니아의표면을 에칭하여상기표면에거칠기를형성하였다.
[98] 상기거칠기가형성된지르코니아의평균표면거칠기는 1.35 이었고，경도는 12.00 GPa이었으며，굴곡강도는 600 MPa이었다.또한상기 생체활성글라스층이 형성된지르코니아에대해세포독성시험 (Cytotoxic test)을테스트하였으며,그 결과는하기표 1에도시되어 있다.
[99] [실시예 3]
[100] 실시예 1의거칠기가형성된지르코니아표면 (생체활성글라스층표면)에
침지법을이용하여수산화아파타이트및생체활성글라스를포함하는 생체무기코팅층을형성하고제 2소결하였다.
[101] 구체적으로，평균입경이 2 ; 이고입도범위가 0.1~10 /αη인수산화아파타이트 분말과제조예 2의 Si02-Al203-Na20계생체활성글라스분말이 15: 1중량비로 혼합된흔합분말과,상기혼합분말 1증량부에 대하여증류수 100중량부가 혼합된혼합액에실시예 1의거칠기가형성된지르코니아를침지하여상기 지르코니아의생체활성글라스층표면에생체무기코팅층을형성한후， 1,000°C에서제 2소결하여생체무기코팅층이형성된지르코니아를제조하였다.
[102] 상기 생체무기코팅층이형성된지르코니아의평균표면거칠기는 2.89
； ffli이었고,굴곡강도는 627 MPa이었다.그리고상기생체무기코팅층이형성된 지르코니아에대해세포독성시험 (Cytotoxic test)을테스트하였으며 ,그결과는 하기표 1에도시되어있다.
[103] [실시예 4]
[104] 실시예 1의거칠기가형성된지르코니아대신실시예 2의거칠기가형성된 지르코니아를사용한것을제외하고，실시예 3과동일하게생체무기코팅층이 형성된지르코니아를제조하였다.
[105] 상기 생체무기코팅층이형성된지르코니아의평균표면거칠기는 2.46
이었고，굴곡강도는 405 MPa이었다.그리고상기생체무기코팅층이형성된 지르코니아에대해세포독성시험 (Cytotoxic test)올테스트하였으며，그결과는 하기표 1에도시되어있다.
[106] [비교예 1]
[107] 실시예 1의거칠기가형성된지르코니아대신제조예 1의 예비소결된 지르코니아를사용한것을제외하고，실시예 3과동일하게생체무기코팅층이 형성된지르코니아를제조하였다.
[108] 그리고상기생체무기코팅층이형성된지르코니아에대해
세포독성시험 (Cytotoxic test)을테스트하였으며，그결과는하기표 1에도시되어 있다.
[109] 본발명에서언급하는굴곡강도는압력이가해졌을때재료가버틸수있는 강도를의미하는것으로，제조예，비교예및실시예에서의굴곡강도는국제규격 ISO 6872에따라측정된것이다.
[110] 상기세포독성시험은각제조예,비교예또는실시예에서제조된것올
시편으로하여다음과같은방법으로측정되었다. 24 well plate에각군당 3개의 시편을넣은후,시편이들어 있는 well에조골모세포 MC3T3-E1(ATCC Catalog No. CRL-2593)를 5xl05 cells/cm2밀도로분주한다음，배양액 1≠ 넣고, 37°C, 5%이산화탄소배양기내에서 24시간배양하였다. 24시간세포배양한후 EZ-Cytox(Itsbio, Korea)를이용하여 1 well딩 · 20 씩정량하였다.이어세포를 37°C, 5%이산화탄소배양기내에서 1시간동안반웅시킨후 96 well plate에 100 ^씩분주하여기포를없앤후흡광도측정기 (Microtplate (ELISA) reader: ELx 800UV®, Bio-Tek Instrument. Inc, USA)를이용하여 450 nm에서각 well의 흡광도를측정하였다.대조파장은 630 nm로하였다.세포배양후，
주사전자현미경사진촬영을위해시편들을고정한다음 PBS로 10분씩 2회 세척하였다.그다음 40%, 50%, 60%, 70%, 80%, 90%에탄을에서각각 15분 간격으로， 100%에탄올에서는 10분간격으로 3회에걸쳐탈수를시행하였다. 이어 370C, 5%이산화탄소배양기내에서시편올건조하고 ion sputter (EX-200®, Hitachi horiba, Japan)를이용하여 1분간백금코팅한후전자주사현미경
(S-4700®, Hitachi horiba, Japan)을이용하여시편표면의세포부착정도및 형태변화를관찰하였다.
[111]
[112] 제조예 2，실시예 1및실시예 2에서와같이，지르코니아표면에형성된
생체활성글라스층에표면거칠기를형성할경우,굴곡강도가현저히
증가하였다.
[113] 특히표면거칠기가형성된후에 생체무기코팅층이더형성된실시예 3의
경우는실시예 1과비교하여굴곡강도가증가하였으나，실시예 4의경우는 실시예 2와비교하여굴곡강도가오히려감소하였디-.따라서보다우수한 굴곡강도를가지는임플란트의제조를위한측면에서산식각방법보다는 샌드블라스팅방법으로표면거칠기를형성하는것이바람직함을알수있다.
[1 14] 제조예 1，제조예 2，실시예 1내지실시예 4의경우의파괴인성올평가하기 위해，각표면에압입 (Indentation)을준후에그표면형상을관찰하였다.그결과， 아무코팅되지않은제조예 1및제조예 2의경우는표면에크랙이
발생하였으나,실시예 1내지실시에 4의경우는표면에크랙발생하지않았다. 특히실시예 3및실시예 4의경우는실시예 1및실시예 2와비교하여표면 요철이그대로나타나는것을확인하였다.이는지르코니아재료와각층의 밀착력및결합력특성향상됨에따른것으로판단된다.따라서다층구조로 코팅된복합임플란트임에도우수한구조안정성을가지는것을알수있다.즉, 표면거칠기가형성된생체활성글라스층에생체무기코팅층이더형성됨에도 표면거칠기가유지되며,그럼에도높은파절저항성을유지하여구조안정성이 확보되는것을알수있다.
[115] 구체적으로,표면거칠기가형성된이후에생체무기코팅층이형성됨에도
생체무기코팅층위로요철이나타나지않는현상없이표면거칠기가유지되는 것은，요철이다양한구조를가짐에따라생체무기코팅층이그위에형성됨에도 요철형상이유지되는것에기인하는것으로판단된다.이러한결과는
생체활성글라스층표면에요철이도입됨에따리ᅳ,점,전위，입계,크랙,접힘， 주름둥의다양한구조적미세요철이도입되는것에기인하는것으로판단된다.
[116] 또한높은표면거칠기가형성됨으로써 ,이에의해세포부착특성도향상됨을 확인하였다.도 1,도 2,도 3및도 4는각각순서대로제조예 1，제조예 2,실시예 1및실시예 2에따른경우의세포부착정도를주사전자현미경을이용하여 관측한세포부착시험 결과를나타낸것이다.구체적으로，상기결과는각제조예 또는실시예에서최종제조된지르코니아에세포를부착하고 24시간이지난 시점에서 100배율로관측한것이다.세포부착시험결과,생체활성글라스층이 형성된제조예 2의 경우 (도 2)는층이형성되지않은제조예 1의 경우 (도 1)보다 오히려더낮은세포부착결과를나타났다.반면，생체활성글라스층이형성된 후에거칠기가형성된실시예 1및실시예 2의 경우는높은세포부착결과를 나타냈다.또한도면에별도로도시하지는않았으나,생체활성글라스충이 형성된후에표면거칠기가형성되고생체무기코팅층이더형성된실시예 3및 실시예 4의경우도실시예 1및실시예 2와마찬가지로높은세포부착결과를 나타내는것올확인하였다.
[117] [표 1]
Figure imgf000018_0001
[119] 상기표 1은제조예 1,제조예 2,실시예 1내지 실시예 4의 경우에 대한 세포독성시험 (Cytotoxic test)을테스트한생체적합성결과를나타낸것이다.
[120] 세포독성시험에서，생체활성글라스층이형성된제조예 2의경우는그렇지 않은제조예 1의경우에비하여세포증식이감소하여오히려생체적합성이 저하되었다.그러나표면거칠기형성과정이수행된실시예 1및실시예 2의 경우，생체적합성이향상되었으며,생체무기코팅층이더형성된실시예 3및 실시예 4의경우,생체적합성이 현저히향상되었다.
[121] 또한실시예로서구체적으로기재하지는않았으나，실시예 3,실시예 4와 동일하게수행하되 생체무기코팅층으로생체활성글라스를포함하지않고 수산화아파타이트만올포함하는것을사용한실시예 5및실시예 6의경우는 각각실시예 3및실시예 4와비교하여굴곡강도，세포부착성및생체적합성 둥의특성이전반적으로떨어졌다.

Claims

청구범위
[청구항 1] 지르코니아를포함하는재료;및
상기재료상에코팅되는생체활성글라스층;을포함하며， 상기생체활성글라스층은산화규소,산화알루미늄,산화나트륨, 산화마그네슘,산화바륨，산화칼슘,산화티타늄및산화니오븀중에서 선택되는어느하나또는둘이상의 생체활성글라스를포함하며, 상기생체활성글라스층의표면에거칠기가형성된것을특징으로하는 임플란트.
[청구항 2] 제 1항에있어서,
상기생체활성글라스층상에코팅되는생체무기코팅층을더포함하며, 상기생체무기코팅층은수산화아파타이트 (Cal0(PO4)6(OH)2, HA), 오산화인 (p205),제 3인산칼슘 (Ca3(P04)2, TCP),옥타인산칼슘 (Cas¾(P04 )6·5Η20, OCP)및옥타인산칼슘 (Ca40(P04)2, 4CP)중에서선택되는어느 하나또는둘이상의생체세라믹을포함하는임플란트.
[청구항 3] 제 2항에 있어서，
상기생체무기코팅층은산화규소,산화알루미늄，산화나트륨, 산화마그네슘，산화바륨,산화칼슘,산화티타늄및산화니오븀중에서 선택되는어느하나또는둘이상의생체활성글라스를더포함하는 임플란트.
[청구항 4] 제 1항에 있어^，
상기생체활성글라스층의표면은 0.5-5.0 의거칠기가형성된것인 임플란트ᅳ
[청구항 5] 저) 1항에 있어서，
상기생체활성글라스는산화철，오산화인，산화붕소,산화칼륨및 산화스트론튬중에서선택되는어느하나또는둘이상을더포함하는 임플란트.
[청구항 6] a)지르코니아를포함하는재료상에생체활성글라스를코팅하여
생체활성글라스층올형성하는단계및
b)상기 생체활성글라스층상에표면거칠기를형성하는단계를 포함하며,
상기생체활성글라스는산화규소,산화알루미늄，산화나트륨, 산화마그네슴,산화바륨,산화칼슘，산화티타늄및산화니오븀중에서 선택되는어느하나또는둘이상을포함하는임플란트의제조방법.
[청구항 7] 제 6항에있어서，
c)표면거칠기가형성된생체활성글라스층상에생체무기코팅층을 형성하는단계를더포함하며，
상기생체무기코팅층은수산화아파타이트 (Ca10(PO4)6(OH)2, HA), 오산화인 (p205),제 3인산칼슘 (Ca3(P04)2, TCP),옥타인산칼슘 (Ca8H2(P04 )6-5H20, OCP)및옥타인산칼슘 (Ca40(P04)2, 4CP)증에서선택되는어느 하나또는둘이상의 생체세라믹을포함하는임플란트의제조방법ᅳ
[청구항 8] 제 7항에 있어서,
상기 생체무기코팅층은산화규소，산화알루미늄,산화나트륨, 산화마그네슘，산화바륨，산화칼슘,산화티타늄및산화니오븀중에서 선택되는어느하나또는둘이상의 생체활성글라스를더포함하는 임플란트의 제조방법.
[청구항 9] 제 7항에 있어서,
상기 a)단계와상기 b)단계사이에 생체활성글라스층을제 1소결하는 단계및
상기 c)단계이후에생체무기코팅층을제 2소결하는단계를더포함하는 임플란트의제조방법.
[청구항 10] 제 9에 있어서,
상기제 1소결은 l,200~1700oC에서수행되며，상기제 2소결은
800~l,200oC에서수행되는것인임플란트의제조방법.
[청구항 11] 제 6항에 있어서,
상기 b)단계의표면거칠기는 0.5~5.0 의평균크기를가지는요철이 형성되는것인임플란트의제조방법.
[청구항 1 제 6항에 있어서，
상기생체활성글라스는산화철，오산화인,산화붕소,산화칼륨및 산화스트론튬중에서선택되는어느하나또는둘이상을더포함하는 임플란트의제조방법.
PCT/KR2017/003829 2016-04-08 2017-04-07 생체활성글라스를 포함하는 지르코니아 임플란트 및 이의 제조 방법 WO2017176090A1 (ko)

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KR1020170044424A KR101951343B1 (ko) 2017-04-05 2017-04-05 생체활성글라스를 포함하는 지르코니아 임플란트 및 이의 제조 방법
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