WO2008123641A1

WO2008123641A1 - Implant fixture comprising hydroxyapatite/alumina/silica composite

Info

Publication number: WO2008123641A1
Application number: PCT/KR2007/003685
Authority: WO
Inventors: Young Min Park; Sang Ho Min; Su Chak Ryu
Original assignee: Dio Corp
Current assignee: Dio Corp
Priority date: 2007-04-06
Filing date: 2007-07-31
Publication date: 2008-10-16
Anticipated expiration: 2009-10-06
Also published as: KR100733726B1

Abstract

Disclosed herein is an implant fixture comprising a hydroxyapatite (Ca10 (PO4)6(OH)2)/alumina (Al2O3)/silica (SiO2) composite, which is used for in vivo implantation in medical fields, including dental surgery, orthopedic surgery, otorhinolaryngology, oral and maxillofacial surgery, plastic surgery, as well as a preparation method thereof. In comparison with the prior fixture made of titanium, the disclosed implant fixture has excellent biocompatibility and rapidly binds to a bone in an initial stage of implantation so as to improve the initial stage fixation of implants. The fixture is very useful, because it can improve the fixation and stability of implants.

Description

IMPLANT FIXTURE COMPRISING HYDROXYAPATITE/ ALUMINA/SILICA COMPOSITE

Technical Field

[1] The present invention relates to an implant fixture, in which small amounts of alumina and silica are added to hydroxyapatite, which is biocompatible and shows excellent bioactivity, such that the mechanical strength of hydroxyapatite is increased without reducing the biocompatibility and bioactivity, and to a preparation method thereof. Background Art

[2] Primary teeth are gradually lost in accordance with the order of eruption thereof from a given point of time to adapt to the growth of jawbones, and permanent teeth replace them. However, the permanent teeth, once lost, do not erupt, and thus medical prostheses for providing teeth replacements upon the decay of permanent teeth or the loss of permanent teeth by accidents have been developed. These prostheses include bridge prosthesis, in which teeth adjacent to missing permanent teeth are ground, and partial or full dental prosthesis, which is carried out if adjacent teeth supporting the bridge teeth do not exist. However, the bridge prosthesis causes damage to healthy teeth, because teeth adjacent to missing teeth are ground. The partial and full dentures are inconvenient in that they are inserted in and removed from oral cavities, and also have problems in that they have foreign body sensation and cause damage to healthy teeth connected to the dentures. For this reason, implant surgery has recently been used.

[3] Generally, the term "dental implants" refers to replacements themselves for lost natural teeth or refers to dental surgery of restoring the original function of teeth by inserting a screw-shaped implant fixture into the jawbone, allowing the inserted fixture to be fused with the bone for a given period of time, and then fixing prostheses such as an abutment and an artificial tooth crown on the fixture. Implants can exhibit a chewing force approximately similar to that of normal teeth, compared to the existing false teeth having a chewing force of only about 30% of natural teeth, and are very superior to the existing other prostheses in terms of the restoration of chewing functions, and aesthetic properties, because teeth on both sides of a missing tooth are not ground, unlike artificial teeth. Thus, in this implant surgery, the excellent biocompatibility of implants being inserted is urgently required, and it is particularly important to allow the implants to be sufficiently bonded with the jawbone as soon as possible, thus increasing the fixation of the implant in the jawbone. [4] Dental implant fixtures, which are currently frequently used to firmly anchor an implant to the jawbone, are unalloyed titanium (Ti) materials, including ASTM grades 3 and 4, and Ti-6A1-4V (ELI). Titanium (Ti) is very easy to use, because it is light, has excellent strength and an elastic modulus similar to that of natural teeth and, at the same time, is biocompatible. However, it was recently found that human beings having genes showing a rejection reaction to titanium exist and the long-term use of titanium shows an erosion phenomenon. Also, in the case of Ti-6A1-4V(ELI), there is a report that toxicity caused by vanadium appears and aluminum is attributable to mental disorders such as Alzheimer's disease. For this reason, scientists have made efforts to find more chemically stable biomaterials with the understanding of complex reactions occurring in vivo. That is, there have been efforts to use, as biomaterials, ceramics which are more chemically stable in the surrounding environment compared to metal or polymer materials. Hydroxyapatite is typical of ceramic materials, which are biocompatible and show bioactivity. However, because hydroxyapatite has low mechanical strength, technology of producing a dental fixture using hydroxyapatite is not yet successful. Disclosure of Invention Technical Problem

[5] Accordingly, in order to use, as an implant fixture, the above-described hydroxyapatite, which is biocompatible and shows bioactivity, the present inventors have made efforts to manufacture an implant fixture having higher mechanical strength by solving the problems occurring in the prior art without affecting the bioactivity of hydroxyapatite and, as a result, have prepared an implant fixture having higher mechanical strength, thereby completing the present invention.

[6] Therefore, it is an object of the present invention to provide an implant fixture, which is prepared by adding alumina and silica to hydroxyapatite, and a preparation method thereof.

[7] Another object of the present invention is to provide an implant fixture for use in dental surgery, orthopedic surgery, otorhinolaryngology, oral and maxillofacial surgery, plastic surgery and the like, which has osseoinductive surface properties and excellent mechanical strength, such that it can be successfully osseointegrated into a patient in a short period of time. Technical Solution

[8] In one aspect, the present invention provides an implant fixture comprising a hy- droxyapatite/alumina/silica composite.

[9] Hydroxyapatite, which is used in the present invention, is the same component as that of the enamel of human bones and teeth and may have the following formula 1 : [10] <foraiula 1>

[11] Ca (PO ) (OH)

10 4 6 2

[12] This hydroxy apatite has a great effect on the restoration of loss of dental enamel and has recently received attention as a tooth whitening agent, because it restores the original color of teeth. In the present invention, hydroxyapatite is intended to be used as a raw material for the implant fixture composite.

[13] Alumina, which is used in the present invention, is also called "aluminum oxide" as a compound of aluminum and oxygen, and is represented by a chemical formula of Al O . It has a molecular weight of 101.96 and is present in various forms, α-alumina, which is produced by heating aluminum hydroxide to a temperature lower than 300⁰C, is in a pure and stable form. In addition, there is γ-alumina having low crystallinity, which is produced by dehydrating β-alumina hydrate containing little alkali, and alumina types such as δ, ζ, η, θ, K χ or p-alumina are also known. In the present invention, all forms of silica, which are represented by a chemical formula of Al O , may be used without a particular limitation.

[14] Silica, which is used in the present invention, is also called "silicon dioxide" as a compound of silicon and oxygen and is represented by a chemical formula of SiO . It is a component in various naturally occurring silicates. Also, it naturally occurs as crystalline or amorphous silica in quartz, cryolite, chalcedony, agate, flint, tridymite cristobalite and the like. In the present invention, all forms of silica, which are represented by a chemical formula of SiO , may be used.

[15] As used herein, the term "implant fixture" refers to a fixture, at least a portion of which is brought into contact with bone tissue or implanted into bone tissue. This implant fixture is used for in vivo implantation in medical fields, including dental surgery, orthopedic surgery, otorhinolaryngology, oral and maxillofacial surgery, plastic surgery and the like, and the implant fixture is not limited only to dental applications as long as it is an implant fixture for in vivo implantation in medical fields.

[16] In the preparation of the implant fixture according to the present invention, bioglass is formed due to the reaction between the Ca and P components of hydroxyapatite and the Si and Al components of silica and alumina. Such bioglass surrounds hydroxyapatite particles, is distributed uniformly throughout the fixture, and thus acts like a binder. Accordingly, the fixture of the present invention has high bioactivity and excellent stability compared to the prior fixtures, because the mechanical strength of hydroxyapatite in the inventive fixture is increased due to the addition of silica and alumina (see Example 3).

[17] In another aspect, the present invention provides a method for preparing said implant fixture, the method comprising the steps of: 1) preparing each of hydroxyapatite, alumina and silica powders as raw materials; 2) ball-milling the raw material powders to regrind and mix them; 3) drying the mixed powders; 4) press-molding the dried powders; and 5) thermally treating the press-molded body, thereby preparing a fixture.

Advantageous Effects

[18] The inventive implant fixture comprising the hydroxyapatite/alumina/silica complex is aesthetic and biologically safe, compared to the prior implant fixture made of titanium. Also, it increases the activity of osteoblasts to induce rapid osseointegration by binding to bone tissues. Thus, the inventive implant fixture provides an effect of increasing the functionality and success rate of implants, which are implanted into patients in medical fields, including dental surgery, orthopedic surgery, otorhino- laryngology, oral and maxillofacial surgery, plastic surgery and the like. Brief Description of the Drawings

[19] FIG. 1 is a flowchart showing a process for preparing an implant fixture comprising a hydroxyapatite/alumina/silica composite according to one embodiment of the present invention;

[20] FIG. 2 is an SEM (scanning electron microscope) photograph of raw material powders for preparing the hydroxyapatite/alumina/silica composite implant fixture comprising a according to one embodiment of the present invention;

[21] FIG. 3 shows the results of XRD analysis conducted in Example 2 for the hydroxyapatite/alumina/silica composite implant fixture sintered at 145O⁰C;

[22] FIG. 4 is an optical microscope photograph showing the osseointegration of fixtures, measured at 3 days and 2 weeks after implanting each of the hydroxyapatite/ alumina/silica composite implant fixture according to one embodiment of the present invention and a titanium fixture into a rabbit's hind leg; and

[23] FIG. 5 shows several colors of the inventive implant fixture comprising the hydroxyapatite/alumina/silica composite. Best Mode for Carrying Out the Invention

[24] Hereinafter, the present invention will be described in detail.

[25] To prepare the implant fixture, high-purity hydroxyapatite (purity of more than 98), alumina and silica fine powders are used as starting materials.

[26] As the fine powders, those passed through a 635-mesh screen are preferably used

(SlO of FIG. 1). In a specific embodiment of the present invention, the volume ratio of hydroxyapatite: alumina: silica is preferably 50-90: 0.5-49.5: 0.5-49.5. In a specific example of the present invention, hydroxyapatite, silica and alumina were used in amounts of 90 vol%, 2 vol% and 8 vol%, respectively (see Example 1).

[27] Herein, the volume ratio of alumina: silica is preferably 7-9: 1-3. Particularly, in a specific example of the present invention, it could be seen that, at the above- specified content ratio, the compressive strength, bending strength and micro Vickers hardness of the implant fixture were significantly increased (see Example 3, Table 2).

[28] Meanwhile, although the shape of hydroxyapatite powder, which is used in the present invention, is not specifically limited, it is preferable to use a combination of spherical powder and a second shape. In this case, the volume ratio of spherical hydroxyapatite: Whisker hydroxyapatite powder is preferably 50-85: 5-40. In a specific example of the present invention, spherical hydroxyapatite and Whisker hydroxyapatite were used in amounts of 80 vol% and 10 vol%, respectively (Example 1).

[29] When spherical hydroxyapatite powder was used in combination with a small amount of Whisker hydroxyapatite, the primary mechanical properties of the implant fixture were further increased (Table 1). Thus, it is preferable to use hydroxyapatite powders having different shapes in combination.

[30] The aspect ratio of Whisker hydroxyapatite powder, which isi used in the present invention, is in the range of 3-15, and preferably 10-15. The average particle size of each of hydroxyapatite, silica and alumina raw material powders is in the range of 0.1-lOOQ, and preferably 0.8-3D.

[31] After each of hydroxyapatite, silica and alumina powders as raw materials is prepared as described above, the raw material powders are re-ground and mixed with each other. To grind and mix the powders, ball milling is performed. Preferably, the powders can be ball-milled in water (wet process) or air (dry process) for 6-48 hours. In a specific example of the present invention, the powders were ball-milled in water for 24 hours (S20 of FIG. 1).

[32] In the next step, the re-ground and mixed powders are dried (S30 of FIG. 1).

Preferably, the dried powders are prepared as mono-dispersed fine spherical particles. The drying of the powders can be carried out in a dryer at a temperature of 80 to 13O⁰C, and preferably 100⁰C. Alternatively, the powders may also be freeze-dried at a temperature of -30 to -8O⁰C, and preferably -5O⁰C. In a specific example of the present invention, the powders were freeze-dried to prepare mono-dispersed fine spherical particles (S30 of FIG. 1). Thus, the particle size distribution of the prepared fine spherical particles is 0.1-lOOD, and preferably 0.8-3D.

[33] In the next step, the dried powders are pressed and molded. Preferably, the dried powders are molded under a pressure of 1-100 Ton/D. In a specific example of the present invention, the powders were molded under 20 Ton/D (S40 of FIG. 1).

[34] The molding process can be carried out using one or more selected from among biaxial pressing, injection molding, hot isostatic pressing (HIP) or cold isostatic pressing (CIP). In a specific example of the present invention, the powders were molded by biaxial pressing, and then cold isotatic pressing (S40 of FIG. 1).

[35] Finally, the press-molded body is thermally treated to prepare an implant fixture.

Herein, the press-molded body can be thermally treated in an electric furnace at 1200-1500⁰C to prepare an implant fixture. More specifically, the press-molded body can be thermally treated at 600⁰C for 2 hour to burn-out a small amount of organic materials, can be compacted at 1200⁰C for 3 hours, and then can be sintered at 1450⁰C, thus preparing an implant fixture. In a specific example of the present invention, the press-molded body was thermally treated at 1450⁰C to prepare an implant fixture (S50 of FIG. 1).

[36] The inventive implant fixture prepared according to the above-described method can be prepared in various colors. Thus, in another aspect, the present invention provides implant fixtures having various colors. In a specific example of the present invention, light blue, light yellow, beige and pure white fixtures were prepared (see FIG. 5). When the implant fixture is used in dental applications, it is preferably prepare to have a color similar to the color of teeth.

[37] Hereinafter, the present invention will be described in further detail with reference to examples. It is to be understood, however that these examples are illustrative only and the scope of the present invention is not limited thereto.

[38] Example 1: Preparation of implant fixture comprising hydroxyapatite/ alumina/silica composite

[39] 1) Volume ratio and formulation of hydroxy apatite/alumina/silica raw material powders for implant fixture

[40] Based on 100 vol% of a fixture, 80 vol% of spherical hydroxyapatite powder having an average particle size of ID, and 10 vol% of Whisker hydroxyapatite, were used. In addition, silica powder and alumina powder were used in amounts of 2 vol% and 8 vol%, respectively.

[41] 2) The raw material powders were re-ground and mixed with each other by ball milling in water (wet process) for 24 hours (S20 of FIG. 1).

[42] 3) The re-ground and mixed powders were freeze-dried at a temperature of -50⁰C to prepare fine spherical particles having a size of 0.9- 1.5D (S30 of FIG. 1).

[43] 4) The prepared fine spherical particles were molded by biaxial pressing under a pressure of 20 ton/D, and then cold isotactic pressing (S40 of FIG. 1).

[44] 5) The press-molded body was burned out at 600⁰C for 2 hours, compacted at 1200⁰C for 3 hours, and then sintered at 1450⁰C, thereby preparing an implant fixture (S50 of FIG. 1). The physical properties of the prepared implant fixture were measured and the measurement results are shown in Table 1 below.

[45] Table 1 [Table 1] [Table ]

[46] As can be seen in Table 1 above, in the case where a mixture of spherical hy- droxyapatite powder and whisker hydroxyapatite (Hap (whisker+particle)) was used, the resulting fixture showed high compressive strength, bending strength and micro Vickers hardness compared to the case where spherical hydroxyapatite was used alone to prepare the fixture. Also, in the case where alumina (Al O ) and silica (SiO ) were added to the mixture of spherical hydroxyapatite powder and whisker hydroxyapatite, the mechanical strength of the hydroxyapatite can further be increased (see Table 1).

[47] Example 2: X-ray diffraction (XRD) analysis of hydroxyapatite/alumina/silica composite

[48] FIG. 3 shows the results of XRD analysis of an implant fixture comprising a hydroxyapatite/alumina/silica composite, sintered at 145O⁰C. As can be seen in FIG. 3, the main peaks of alumina and silica did not appear, even though the composite containing silica and alumina was sintered. This is thought to be because the Ca and P components of hydroxyapatite reacted with Si and Al to form bioglass, and thus Si and Al were not detected in the XRD analysis. The bioglass surrounds the HAp particles, is distributed uniformly throughout the fixture, and thus acts like as a binder. Such bioglass is formed by the reaction between the Ca and P components of hydroxyapatite and the Si and Al components of silica and alumina.

[49] Example 3: Compressive strength, bending strength and micro-hardness according to composition ratio of implant fixture

[50] Several typical compositions of implant fixtures comprising a hydroxyapatite/ alumina/silica composite were prepared in the same manner as in Example 1, sintered at 145O⁰C, and then measured for compressive strength, bending strength and micro Vickers hardness. The measurement results are shown in Table 2 below. As can be seen in Table 2, the compressive strength, bending strength and micro- Vickers hardness of the fixtures were increased in a composition ratio range of HAp:Al O :SiO of 90:5:5 to 90:8:2, but were decreased at a composition ratio of 90:9: 1.

[51] Table 2 [Table 2] [Table ]

[52] As can be seen from the results of Table 2 above, the binding force of bioglass to hy- droxyapatite started to increase from a composition ratio of HAp:A12O3:SiO2 of 90:5:5 and reached the highest at a composition ratio of HAp:A12O3:SiO2 of 90:8:2. Following the composition ratio showing the highest binding strength, the amount of bioglass formed was decreased, so that the binding force of bioglass to hydroxyapatite was reduced, thus reducing the compressive strength, bending strength and micro- Vickers hardness of the fixtures.

[53] Example 4: Preparation of implant fixtures having various colors [54] FIG. 5 shows cylinder-type or screw-type implant fixtures comprising a hy- droxyapatite/alumina/silica composite, which have various colors. As shown in FIG. 5, the implant fixtures could be prepared to have various colors, such as light blue, light yellow, beige and pure white colors. Hydroxyapatite powder has a white, light yellow or light blue color; the use of blue color hydroxyapatite can prepare a blue color implant fixture. Also, a pure white, beige or light yellow fixture can be obtained by controlling the amounts of alumina and silica added. Herein, when alumina is added in an amount large than silica, a fixture having a color close to white can be obtained, and when silica is added in an amount larger than alumina, a fixture having a color close to light yellow can be obtained.

[55] Test Example: Tissue reaction of implant fixture comprising hydroxyapatite/ alumina/silica composite, implanted into rabbit's hind leg [56] The implant fixture comprising the hydroxyapatite/alumina/silica composite, prepared in Example 1, was implanted into a rabbit's hind leg, and after 3 days and 2 weeks, the degree of osseointegration of the fixture was observed.

[57] FIG. 4 shows an optical microscope photograph showing the osseointegration of fixtures, measured at 3 days and 2 weeks after implanting each of the hydroxyapatite/ alumina/silica composite implant fixture and a titanium fixture into a rabbit's hind leg. As can be seen in FIG. 4, in the case of the prior titanium (Ti) fixture, a new bone produced around the fixture did not react with the fixture, and even after weeks, only the periosteum was formed. However, in the case where the implant fixture comprising the hydroxyapatite/alumina/silica was implanted, with the passage of time from 3 days to 2 weeks, not only the periosteum was formed around the fixture, but also osteoblasts, fibrous tissues and cementums were produced, and thus the osseointegration of the fixture rapidly occurred. Through this test example, it could be seen that the implant fixture prepared according to the present invention showed a high degree of osseointegration compared to the prior implant fixture made of pure titanium (Ti).

[58] As described above, the inventive implant fixture comprising the hydroxyapatite/ alumina/silica complex is aesthetic and biologically safe, compared to the prior implant fixture made of titanium. Also, it increases the activity of osteoblasts to induce rapid osseointegration by binding to bone tissues. Thus, the inventive implant fixture provides an effect of increasing the functionality and success rate of implants, which are implanted into patients in medical fields, including dental surgery, orthopedic surgery, otorhinolaryngology, oral and maxillofacial surgery, plastic surgery and the like.

[59] While the invention has been described in connection with what is presently considered to be practical exemplary embodiments, it is to be understood that the invention is merely exemplary and not limited to the disclosed embodiments. Therefore, a person skilled in the art can perform various changes and modifications based on a principle of the present invention, which falls in the scope of the present invention.

[60]

[61]

Claims

[I] An implant fixture comprising a hydroxy apatite/alumina/silica complex.

[2] The implant fixture of Claim 1, wherein the hydroxyapatite/alumina/silica complex is in a sintered state.

[3] The implant fixture of Claim 1, wherein bioglass formed by the reaction between the Ca and P components of said hydroxyapatite and the Si and Al components of said silica and alumina is distributed in the fixture.

[4] The implant fixture of Claim 1, wherein the volume ratio of said hydroxyapatite: alumina: silica is 50-90: 0.5-49.5: 0.5-49.5.

[5] The implant fixture of Claim 4, wherein the contents of said hydroxyapatite, silica and alumina in the composite are 90 vol%, 2 vol% and 8 vol%, respectively.

[6] The implant fixture of Claim 1, wherein the volume ratio of said alumina: silica is 7-9 : 1-3.

[7] The implant fixture of Claim 1, wherein said hydroxyapatite is a mixture of spherical powder and whisker powder.

[8] The implant fixture of Claim 7, wherein the volume ratio of said spherical hydroxyapatite powder: whisker powder is 50-85: 5-40.

[9] The implant fixture of Claim 1, which is used in dental surgery, orthopedic surgery, otorhinolaryngology, oral and maxillofacial surgery, or plastic surgery applications.

[10] A method for preparing an implant fixture, the method comprising the steps of:

1) preparing each of hydroxyapatite, alumina and silica powders as raw materials;

2) ball- milling the raw material powders to regrind and mix the powders;

3) drying the mixed powders;

4) press-molding the dried powders; and

5) thermally treating the press-molded body, thereby preparing a fixture.

[I I] The method of Claim 10, wherein the average particle size of each of the powders in the step 1) is 1-lOOD.

[12] The method of Claim 10, wherein the drying in the step 3) is carried out in a dryer at a temperature of 80 to 13O⁰C, or is carried out by freeze drying at a temperature -30 to -8O⁰C. [13] The method of Claim 10, wherein the average particle size of the dried powders in the step 4) is 0.8-3D. [14] The method of Claim 10, wherein the press-molding in the step 4) is performed by carrying out one or more of biaxial pressing, injection molding, hot isostatic pressing (HIP) and cold isostatic pressing (CIP). [15] The method of Claim 10, wherein the pressing in the step 4) is carried out under a pressure of 1-100 ton/D. [16] The method of Claim 14, wherein the pressing in the step 4) is carried out under a pressure of 20 ton/D. [17] The method of Claim 10, wherein the press-molded body in the step 5) is thermally treated at a temperature of 1200-1500⁰C. [18] The method of Claim 10, wherein the press-molded body is thermally treated using an electric furnace.