WO2010087427A1 - 骨修復材料とその製造方法 - Google Patents
骨修復材料とその製造方法 Download PDFInfo
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- WO2010087427A1 WO2010087427A1 PCT/JP2010/051196 JP2010051196W WO2010087427A1 WO 2010087427 A1 WO2010087427 A1 WO 2010087427A1 JP 2010051196 W JP2010051196 W JP 2010051196W WO 2010087427 A1 WO2010087427 A1 WO 2010087427A1
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- aqueous solution
- acid
- surface layer
- titanium
- apatite
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
-
- 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
- A61L27/02—Inorganic materials
- A61L27/04—Metals or alloys
- A61L27/06—Titanium or titanium alloys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
- A61F2/30771—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
- A61F2002/30838—Microstructures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/02—Prostheses implantable into the body
- A61F2/30—Joints
- A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
- A61F2/30771—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth applied in original prostheses, e.g. holes or grooves
- A61F2002/3084—Nanostructures
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00011—Metals or alloys
- A61F2310/00023—Titanium or titanium-based alloys, e.g. Ti-Ni alloys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00389—The prosthesis being coated or covered with a particular material
- A61F2310/00592—Coating or prosthesis-covering structure made of ceramics or of ceramic-like compounds
- A61F2310/00598—Coating or prosthesis-covering structure made of compounds based on metal oxides or hydroxides
- A61F2310/00616—Coating made of titanium oxide or hydroxides
-
- 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
- A61L2400/00—Materials characterised by their function or physical properties
- A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
-
- 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
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants
Definitions
- the present invention relates to a bioactive bone repair material and a manufacturing method thereof.
- This bioactive bone repair material can be suitably used for bone repair in a portion to which a large load is applied such as a femur, a hip joint, a spine, and a tooth root.
- Titanium or its alloy with an apatite layer formed on its surface has great fracture toughness and is bonded to living bone through apatite in vivo, so it is expected as a bone repair material in areas where large loads are applied. Yes. Since the apatite layer formed in advance in vitro is easy to peel off, titanium or its alloy bone on which a titanate layer having an apatite forming ability is formed on the surface in order to form apatite in the body and simultaneously bond with the living bone.
- Various methods for manufacturing a restoration material have been proposed (Patent Document 1, Non-Patent Document 1).
- Various methods for producing a bone repair material in which a titanium oxide layer is formed have also been proposed (Patent Literature 2, Non-Patent Literature 2-8).
- the titanate layer (Patent Document 1, Non-Patent Document 1) elutes sodium ions and calcium ions from the surface in the living body and disturbs the surrounding body fluid environment.
- the titanium oxide layer (Patent Document 2, Non-Patent Documents 2 and 5-7) formed on the surface by the final treatment with water or an acidic aqueous solution has poor apatite forming ability.
- the surface layer treated with hydrogen peroxide (Non-patent Document 3) has poor scratch resistance, and the surface layer formed by anodic oxidation (Non-patent Document 4) contains deep holes unevenly, and bacteria are It is difficult to sterilize through the hole.
- Non-Patent Document 8 The uneven layer formed by cutting (Non-Patent Document 8) has a portion where apatite is not formed, and has poor uniformity of forming ability. Therefore, an object of the present invention is to provide a bone repair material that is difficult to elute ions in vivo, is excellent in apatite forming ability and apatite peeling resistance, and has a practical scratch resistance.
- the bone repair material of the present invention is A substrate having an unevenness of 1 nm or more and 10 ⁇ m or less on average on the surface both in width and depth, and made of titanium or a titanium alloy; A surface layer formed along the surface of the base material, substantially made of titanium oxide, and having a zeta potential of +4.5 mV or higher, preferably +5.0 mV or higher in an aqueous solution environment having a pH of 6 to 8. It is characterized by. According to the bone repair material of the present invention, since the surface layer is made of titanium oxide, ions are hardly eluted in the living body.
- the surface layer is positively charged in an aqueous solution environment as described above, the surface layer is similarly charged in a body fluid environment which is a kind of the aqueous solution, and phosphate ions and calcium ions are adsorbed in this order.
- an apatite layer is formed on the entire surface layer within 1 day, and at most 3 days.
- corrugation of 1 nm or more and 10 micrometers or less on average fulfill
- the phase of titanium oxide may be either a rutile type or an anatase type, and may be another type.
- Suitable methods for producing the bone repair material of this invention include: Prepare a substrate made of titanium or a titanium alloy, form irregularities with an average width of 1 nm or more and 10 ⁇ m or less on the surface of the substrate, soak in an acidic aqueous solution with a pH of 3 or less, wash with water, and then heat It is characterized by doing.
- the base material to be prepared may be titanium alloy such as Ti-6Al-4V and Ti-15Zr-4Nb-4Ta in addition to pure titanium.
- Examples of means for forming the unevenness on the surface include alkali treatment or sand blasting.
- the surface layer of the base material is modified to a titanate phase simultaneously with the formation of irregularities, and then further modified to a titanic acid phase by washing with water.
- the surface layer is modified to a titanium oxide phase by subsequent acid treatment or oxidation.
- One preferable means for forming irregularities is alkali treatment. This is because uniform irregularities having an average width of 1 to 100 nm are formed.
- the acidic aqueous solution examples include hydrochloric acid, sulfuric acid, nitric acid, hydrofluoric acid, and aqueous solutions of these mixed acids.
- the temperature of the acidic aqueous solution is preferably 0 to 100 ° C., and the immersion time is preferably 0.5 to 100 hours.
- the fact that the surface layer is positively charged in an aqueous solution environment also means that acid groups constituting acids such as sulfuric acid, nitric acid, hydrochloric acid, and hydrofluoric acid remain on the surface of titanium oxide.
- the formation of the unevenness may be performed by treating with the same or different acidic aqueous solution as the acidic aqueous solution. If the same acidic aqueous solution is used, unevenness formation and surface modification can proceed simultaneously. According to this method, although depending on the pH of the acidic aqueous solution and the processing time, relatively large and uniform irregularities having an average width of 1 ⁇ m or more and 10 ⁇ m or less can be formed. The pH of the preferable acidic aqueous solution for forming irregularities is 1 or less.
- any manufacturing method it is important to manage the washing process.
- the zeta potential is +4. This is because the voltage drops to less than 5 mV.
- the preferred water washing time is 10 seconds or more and 1 minute or less. However, when washing with warm water or running water, it may take less than 10 seconds, and when washing with cold water, it may take more than 1 minute.
- the heating temperature after washing with water is usually 450 to 750 ° C. or less, preferably 500 to 700 ° C.
- the heating time is preferably 0.5 to 48 hours.
- the bone repair material of the present invention does not harm the living body because ions are hardly eluted in the living body. Further, since it has a practical scratch resistance, the surface layer does not peel off when implanted in the body. And since it is excellent in apatite formation ability, it can couple
- SBF simulated body fluid
- an aqueous solution of sodium hydroxide, potassium hydroxide, or calcium hydroxide, or a mixture thereof can be used for the alkali treatment as a preliminary process for forming irregularities.
- concentration, temperature, and time are not limited. In general, the higher the concentration, the higher the temperature, and the longer the time, the deeper the unevenness.
- blast particles that do not interfere with subsequent chemical treatment (acid treatment or oxidation), such as calcium phosphate particles. Acid resistant particles such as alumina particles are not preferred because they remain on the surface and interfere with subsequent acid treatment.
- any one of hydrochloric acid, sulfuric acid, nitric acid, hydrofluoric acid, or a mixed acid thereof can be used.
- concentration, temperature, and time are not limited.
- Example 1 A pure titanium metal plate having a size of 10 mm ⁇ 10 mm ⁇ 1 mm was prepared and polished with # 400 diamond polishing paper in order to align the initial conditions. This plate was ultrasonically washed with acetone, 2-propanol and ultrapure water in order for 30 minutes each and then immersed in 5 ml of 5M aqueous sodium hydroxide solution at 60 ° C. for 24 hours (hereinafter referred to as “alkali treatment”). As shown in FIG. 2, irregularities having an average depth of 1 ⁇ m and an average pore diameter of 17 nm were formed on the surface.
- the plate was placed in a SiC electric furnace, heated to 600 ° C. at a rate of 5 ° C./mn, held at 600 ° C. for 1 hour, and allowed to cool in the furnace to obtain a bone repair material sample. .
- Example 5 A pure titanium metal plate having the same size as in Example 1 was polished and washed in the same manner as in Example 1. After that, by immersing in 20 ml of a mixed solution of 66.3 wt% sulfuric acid H 2 SO 4 aqueous solution and 10.6 wt% hydrochloric acid HCl aqueous solution at 70 ° C. for 1 hour, an average depth of 1 ⁇ m as shown in FIG. Irregularities having a pore diameter of 1 ⁇ m were formed. The pH of the mixture was close to zero. The titanium metal plate was washed with ultrapure water in the same manner as in Example 1 and heated at 600 ° C. to produce a sample.
- Example 1 a sample was produced under the same conditions as in Example 1 except that the acidic aqueous solution was a 0.5 mM aqueous HCl HCl solution having a pH of 3.45. This manufacturing method is the same as the method described in Non-Patent Document 2.
- -Comparative Example 2- In Example 1, a sample was produced under the same conditions as in Example 1 except that heating was not performed.
- -Comparative Example 3- In Example 1, a sample was manufactured under the same conditions as in Example 1 except that the holding temperature of the electric furnace was 400 ° C.
- -Comparative Example 4- In Example 1, a sample was manufactured under the same conditions as in Example 1 except that the holding temperature of the electric furnace was 800 ° C.
- -Comparative Example 5- In Example 5, a sample was produced under the same conditions as in Example 5 except that heating was not performed.
- Example 7 The same pure titanium metal plate as in Example 1 was polished and washed in the same manner as in Example 1. Then, it was immersed in a solution in which 98% H 2 SO 4 , 36% HCl and water were mixed at a volume ratio of 1: 1: 1 for 1 hour at 60 ° C. and washed in ion-exchanged water subjected to ultrasonic waves for 15 minutes. did. Thereafter, the plate is immersed in 60 ml of a solution (pH ⁇ 0) of 65% HNO 3 and water mixed at a volume ratio of 1: 1 at 60 ° C. for 600 minutes and washed in ion-exchanged water subjected to ultrasonic waves for 15 minutes. Samples were produced. This manufacturing method is the same as the method showing the most excellent apatite forming ability among the methods described in Non-Patent Document 5.
- Example 8 The same pure titanium metal plate as in Example 1 was polished in the same manner as in Example 1 and was mixed in 10 ml of a solution prepared by mixing 48% HF, 62% HNO 3 and water at a volume ratio of 1: 1.5: 6 for 2 minutes. After washing, it was immersed in 20 ml of a solution (pH ⁇ 0) in which 97% H 2 SO 4 and 30% H 2 O 2 were mixed at a volume ratio of 1: 1 at 40 ° C. for 1 hour, washed with distilled water, The temperature was raised to 400 ° C. at a rate of 5 ° C./min, held at 400 ° C. for 1 hour, and then allowed to cool in a furnace to produce a sample. This manufacturing method is the same as the method described in Non-Patent Document 6.
- Example 9 The same pure titanium metal plate as in Example 1 was polished and washed in the same manner as in Example 1, and then an aqueous solution (pH: 98% H 2 SO 4 , 36% HCl and water mixed at a volume ratio of 1: 1: 1). ⁇ 0) It was immersed in 20 ml at 60 ° C. for 1 hour, washed in ion-exchanged water subjected to ultrasonic waves for 15 minutes, and then heated under the same conditions as in Example 1. This manufacturing method is the same as one of the methods described in Non-Patent Document 7.
- Example 1 The sample of Example 1 was immersed in simulated body fluid of ISO standard 23317 for various times and subjected to X-ray photoelectron spectroscopic analysis of the surface. As shown in FIG. 4, first, phosphate ions were adsorbed on the sample, Next, the phenomenon of calcium ion adsorption was observed. When the same analysis was performed on the other samples, as shown in Table 1, in all of the samples of the examples, first, phosphate ions were adsorbed and then calcium ions were adsorbed.
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Abstract
Description
それ故、この発明の課題は、生体内でイオンが溶出しにくく、アパタイト形成能及びアパタイトの耐剥離性に優れ、実用的なひっかき抵抗を有する骨修復材料を提供することにある。
表面に幅及び深さともに平均で1nm以上10μm以下の凹凸を有し、チタンもしくはチタン合金からなる基材と、
前記基材の表面に沿って形成され実質的に酸化チタンからなり、pH=6~8の水溶液環境下で+4.5mV以上、好ましくは+5.0mV以上のゼータ電位を有する表面層と
を備える
ことを特徴とする。
この発明の骨修復材料によれば、表面層が酸化チタンからなるので、生体内でイオンが溶出しにくい。しかも表面層が前記の通り水溶液環境下で正に帯電するものであることから、前記水溶液の一種である体液環境下でも同様に帯電し、リン酸イオン及びカルシウムイオンをこの順序で吸着させる。その結果、表面層の上全体に1日以内、長くても3日以内にアパタイトの層が形成される。そして、平均1nm以上10μm以下の凹凸は、生体内で表面に形成されるアパタイト層及びアパタイト層を介して結合する生体骨を基材に強固に結合させる機能を果たす。尚、酸化チタンの相は、ルチル型、アナターゼ型のいずれでもよく、他の型であっても差し支えない。
チタンもしくはチタン合金からなる基材を準備し、基材の表面に幅及び深さともに平均で1nm以上10μm以下の凹凸を形成し、pHが3以下の酸性水溶液に浸漬し、水洗した後、加熱することを特徴とする。
準備する基材は、純チタンの他、Ti-6Al-4V、Ti-15Zr-4Nb-4Taなどのチタン合金であってもよい。
前記酸性水溶液としては、塩酸、硫酸、硝酸、フッ酸、あるいはこれらの混酸の水溶液が挙げられる。酸性水溶液の温度は0~100℃、浸漬時間は0.5~100時間が好ましい。
尚、表面層が水溶液環境下で正に帯電するということは、酸化チタンの表面に硫酸、硝酸、塩酸、フッ酸などの酸を構成する酸基が残存していることをも意味する。
-実施例1-
10mm×10mm×1mmの大きさの純チタン金属板を準備し、初期条件を揃えるために#400のダイヤモンド研磨紙で研磨した。この板を、アセトン、2-プロパノール及び超純水で順に各30分間超音波洗浄した後、5Mの水酸化ナトリウム水溶液5mlに60℃で24時間浸漬することによって(以下、「アルカリ処理」という)、その表面に図2に示すように平均深さ1μm、平均孔径17nmの凹凸を形成させた。このチタン金属板をpH=1.47の50mM塩酸HCl水溶液10mlに40℃で24時間浸漬し、25℃の超純水で30秒間洗浄した。この板をSiC電気炉に入れ、空気中で600℃まで5℃/mnの速度で昇温し、600℃で1時間保持して炉内で放冷することによって骨修復材料の試料を得た。
実施例1において、電気炉内の保持温度を700℃としたことを除く他は実施例1と同じ条件で試料を製造した。
-実施例3-
実施例1において、酸性水溶液をHCl水溶液に代えてpH=1.46の50mM硝酸HNO3水溶液としたことを除く他は、実施例1と同じ条件で試料を製造した。
-実施例4-
実施例1において、酸性水溶液をHCl水溶液に代えてpH=1.98の10mM硫酸H2SO4水溶液としたことを除く他は実施例1と同じ条件で試料を製造した。
実施例1と同じ大きさの純チタン金属板を、実施例1と同様に研磨して洗浄した。その後、66.3wt%硫酸H2SO4水溶液と10.6wt%塩酸HCl水溶液の混液20 mlに70℃で1時間浸漬することによって、その表面に図3に示すように平均深さ1μm、平均孔径1μmの凹凸を形成させた。同混液のpHは0に近かった。このチタン金属板を実施例1と同様に超純水で洗浄し、600℃で加熱することによって試料を製造した。
実施例1において、酸性水溶液をpH3.45の0.5mM塩酸HCl水溶液としたことを除く他は実施例1と同じ条件で試料を製造した。この製造方法は、非特許文献2に記載された方法と同じである。
-比較例2-
実施例1において、加熱をしないことを除く他は実施例1と同じ条件で試料を製造した。
-比較例3-
実施例1において、電気炉の保持温度を400℃としたことを除く他は実施例1と同じ条件で試料を製造した。
-比較例4-
実施例1において、電気炉の保持温度を800℃としたことを除く他は実施例1と同じ条件で試料を製造した。
-比較例5-
実施例5において、加熱をしないことを除く他は実施例5と同じ条件で試料を製造した。
実施例1と同じ純チタン金属板を、実施例1と同様に研磨し洗浄した。その後、8.8M過酸化水素H2O2と0.1M塩酸HClの混液(pH=1)10mlに80℃で30分間浸漬し、超純水で30秒間洗浄した。この板をSiC電気炉に入れ、空気中で400 ℃まで5℃/minの速度で昇温し、400℃で1時間保持し、炉内で放冷することによって試料を製造した。この製造方法は、非特許文献3に記載された方法の中で、最も優れたアパタイト形成能を示す方法と同じである。
実施例1と同じ純チタン金属板を、実施例1と同様に研磨し洗浄した。その後、98%H2SO4と36%HClと水を1:1:1の体積比で混ぜた溶液中に、60℃で1時間浸漬し、超音波をかけたイオン交換水中で15分間洗浄した。その後この板を65%HNO3と水を1:1の体積比で混ぜた溶液(pH≒0)20ml中に60℃で600分浸漬し、超音波をかけたイオン交換水中で15分間洗浄することによって試料を製造した。この製造方法は、非特許文献5に記載された方法の中で、最も優れたアパタイト形成能を示す方法と同じである。
実施例1と同じ純チタン金属板を、実施例1と同様に研磨し、48%HFと62%HNO3と水を1:1.5:6の体積比で混ぜた溶液10ml中で2分間洗浄した後、97%H2SO4と30%H2O2を1:1の体積比で混ぜた溶液(pH≒0)20ml中に40℃で1時間浸漬し、蒸留水で洗浄後、400℃まで5℃/minの速度で昇温し、400℃で1時間保持した後、炉内で放冷することによって試料を製造した。この製造方法は、非特許文献6に記載された方法と同じである。
実施例1と同じ純チタン金属板を、実施例1と同様に研磨し洗浄した後、98%H2SO4と36%HClと水を1:1:1の体積比で混ぜた水溶液(pH≒0)20mlに60℃で1時間浸漬し、超音波をかけたイオン交換水中で15分間洗浄した後、実施例1と同じ条件で加熱した。この製造方法は、非特許文献7に記載された方法の1つと同じである。
実施例および比較例の試料の表面層の構成相を薄膜X線回折法により調べると、表1に示すように同試料は、アナターゼ型あるいはルチル型の酸化チタン(TiO2)あるいはチタン酸(H2Ti3O7)、水素化チタン(TiH2)などを析出していた。擬似体液中で高いアパタイト形成能を示す試料(実施例1~5)は、アナターゼ型かルチル型の酸化チタンを析出していた。ただし、酸化チタンを析出した試料でも高いアパタイト形成能を示さない試料もあった(比較例1,4,6,8,9)。
株式会社レスカ製のスクラッチ試験機CSR-2000を用いて、バネ定数200g/mmのスタイラスに試料上で100μmの振幅を与え、100mN/minの荷重を印加しながら、スタイラスを10mm/secの速度で移動させた。このときの臨界ひっかき強度を測定した。その結果、表1に示すようにその抵抗は、600℃~700℃の温度で加熱した試料(実施例1~5、比較例1,9)は40mN以上の高い値を示したが、非加熱試料(比較例2,5,7)及び400℃以下(比較例3,6,8)及び800℃以上で加熱した試料(比較例4)は33mN以下の値しか示さなかった。
実施例および比較例の試料を10mM塩化ナトリウムNaCl水溶液に浸漬し、ポリスチレンラテックスの粒子をモニター粒子としてレーザー電気泳動装置(大塚電子、ELS-ZI型)により測定した。測定結果を表1に示す。表の測定データのうち、スラッシュ記号の左側は試料基板をアースで放電した後に測定して得られたデータ、右側はそのような放電処理をせずに測定して得られたデータである。表に示すように、実施例の試料はすべて5.0mV以上の高い正のゼータ電位を示したが、比較例の試料はすべて4.0mV以下のゼータ電位しか示さなかった。表1においては、非加熱試料についてもゼータ電位が記載されている。しかし、非加熱試料は高い電気伝導度を示すので、電荷をほとんど蓄積しない。このため、非加熱試料について測定された絶対値の小さいゼータ電位は、正であれ負であれ、いずれもほぼ零であることだけを意味する。
実施例1の試料をISO規格23317の擬似体液に種々の時間浸漬し、その表面のX線光電子分光分析を行ったところ、図4に示すように同試料上に先ずリン酸イオンが吸着し、次いでカルシウムイオンが吸着する現象が観察された。他の試料についても同様の分析を行うと、表1に示すように実施例の試料ですべて、先ずリン酸イオンが吸着し、次いでカルシウムイオンが吸着した。これらの試料においては、すべてその表面が正の電荷を帯びて高いゼータ電位を有するので、先ず負に帯電したリン酸イオンが吸着し、その表面がリン酸イオンにより負に帯電するに伴って、正に帯電したカルシウムイオンが吸着するためである。これに対し、比較例1、4、6、9以外の比較例の試料はすべて、リン酸イオンとカルシウムイオンがほぼ同時に吸着するか、もしくはカルシウムイオンの吸着がリン酸イオンの吸着に先行した。
実施例1の試料を36.5℃に保ったISO規格23317の擬似体液(SBF)に浸漬したところ、図5に示すように1日以内にその表面がアパタイトで覆い尽くされた。このアパタイト形成能を+++で表すと、実施例のすべての試料は表1に示すように、+++のアパタイト形成能を有していた。一方、比較例1の試料を同様にSBFに浸漬したところ、図6に示すように1日以内ではその表面がまばらにしかアパタイトに覆われなかった。この程度のアパタイト形成能を++で表すと、比較例のすべての試料は表1に示すように0か+か++のアパタイト形成能しか有していなかった。尚、0はアパタイトが全く形成されなかったことを表し、+はアパタイトがかろうじて見いだされる程度のアパタイト形成能を表す。
実施例3及び4の試料の表面をX線光電子分光法(XPS)で分析したところ、それぞれ図7及び図8に分析結果をXPSスペクトルで示すように、実施例3の試料表面で窒素原子、実施例4の試料表面で硫黄原子が検出された。これは、正の電荷と対をなす硫酸イオン、硝酸イオン、塩化物イオンなどの陰イオンを構成する硫黄や窒素などの原子が表面層を構成する酸化チタンの表面に吸着していることを示し、プラスのゼータ電位が観察されることに加えて酸化チタンの表面に酸基が残存していることを裏付けるものである。
Claims (8)
- 表面に幅及び深さともに平均で1nm以上10μm以下の凹凸を有し、チタンもしくはチタン合金からなる基材と、
前記基材の表面に沿って形成され実質的に酸化チタンからなり、pH=6~8の水溶液環境下で+4.5mV以上のゼータ電位を有する表面層と
を備えることを特徴とする骨修復材料。 - バネ定数200g/mmのスタイラスに前記表面層上で100μmの振幅を与え、100mN/minの荷重を印加しながら、スタイラスを10mm/secの速度で移動させたとき、前記表面層が35mN以上の臨界ひっかき強度を有する請求項1に記載の骨修復材料。
- 前記表面層が酸を構成する酸基を含有する請求項1に記載の骨修復材料。
- チタンもしくはチタン合金からなる基材を準備し、この基材の表面に幅及び深さともに平均で1nm以上10μm以下の凹凸を形成し、pHが3以下の酸性水溶液に浸漬し、水洗した後、450℃以上750℃以下で加熱することを特徴とする骨修復材料を製造する方法。
- 前記凹凸の形成が、アルカリ処理することによってなされる請求項4に記載の製造方法。
- 前記酸性水溶液が、塩酸、硫酸、硝酸、フッ酸、あるいはこれらの混酸の水溶液である請求項4に記載の製造方法。
- 前記凹凸の形成が、前記酸性水溶液と同一の又は異なる酸性水溶液で処理することによってなされる請求項4に記載の製造方法。
- 前記水洗の時間が、10秒以上1分以内である請求項4~7のいずれかに記載の製造方法。
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JP2013236700A (ja) * | 2012-05-14 | 2013-11-28 | Chube Univ | 抗菌性骨修復材料及びその製造方法 |
JP2015136553A (ja) * | 2014-01-24 | 2015-07-30 | 学校法人中部大学 | Peekを基材とする骨修復材料及びその製造方法 |
WO2019026539A1 (ja) * | 2017-08-01 | 2019-02-07 | 石原産業株式会社 | 立体構造物及びその製造方法並びに被覆処理装置 |
US11576997B2 (en) | 2018-03-05 | 2023-02-14 | Chubu University Educational Foundation | Iodine-loaded bone repair material and method for producing the same |
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