KR100388074B1 - Implant coated by calcium phosphate thin film - Google Patents

Abstract

The present invention relates to a calcium-phosphorus implant (Ca-P implant) coated with ultra-thin calcium phosphate (calcium phoshate), and more specifically to implants, which are medical devices for biomedical use, include calcium salt and phosphate salts. The present invention relates to a calcium-phosphorus implant having a super thin film coating with a supersaturated calcium phosphate solution using a phosphate salt, which has excellent adhesion between the implant and the coating layer and high bone bonding ability with the living bone. Calcium-phosphorus implant of the present invention is a calcium phosphate ultra-thin coating is excellent in bioreactivity, a wide reaction surface area, excellent adhesion between the implant and the coating layer and high osseointegration, dental surgery, trauma, orthopedic, maxillofacial and mandibular surgery And it can be usefully used as a biomedical medical instrument for veterinary surgery and the like.

Description

Implant coated by calcium phosphate thin film

The present invention relates to ultra-thin calcium-phosphorus implants coated with calcium phosphate. More specifically, the implants, which are biomedical devices, are coated with ultra-saturated calcium phosphate solutions using calcium salts and phosphate salts, thereby improving adhesion between the implant and the coating layer. The present invention relates to a calcium-phosphorus implant that is excellent and has high bone bonding ability with living bone.

Calcium phosphate crystals are known to be biocompatibility. Among them, apatite crystals exist only in biocalcified tissue (Kim, HM et al., J. Bone-Miner. Res ., 10, 1589-1601, 1995; US Pat. No. 5,565,502; and US Pat. No. 5,691,397), which has been used as a bone graft substitute. In addition, apatite crystals have been widely used as solid particles for forming apatite crystal films on surfaces of biomaterials made of metals and contacting tissues to increase the suitability of tissues (Greesink, RGT et al., Clin Orthop.Relat.Res ., 261, 39-58, 1990; Dunn, MG and Maxian, SH, J. Long Term Effect.Med.Implants, 1, 193-203, 1992).

Pure hydroxyapatite crystals composed of calcium ions, phosphate ions, and hydroxy ions are stoichio- metric crystals with a long rod-like structure and have high crystallinity. On the other hand, biocrystals isolated from bone or calcified cartilage have low crystallinity as nonstoichio-metric apatite (Elliott, JC et al., Studies in Inorganic Chemistry, 18, 111). -190, 1994). Biocrystals are very small, thin plate-shaped nanocrystals (27.3 X 15.8 nm for bone, 103 X 68 nm for calcified cartilage tissue; length X width), with a specific surface area. ), Because of its wide reactivity, it exhibits high metabolic activity (Kim, HM et al., J. Bone-Miner. Res ., 10, 1589-1601, 1995; Posner AS et al. , Skeletal Research : An Experimental Approach, Academic Press: New York, 167-192, 1979).

Studies of membranes with nanocrystal crystals similar to those of biocrystals have resulted in the development of ultra-low calcium phosphate thin films, which are characterized in that calcium phosphate crystals are dissolved in aqueous solution by lowering the temperature or optionally selecting an appropriate buffer system. Ultra-thin film with nanocrystal crystals formed in a short time using supersaturated solution of calcium and phosphate ions prepared by inhibiting the precipitation reaction. : 98-38553).

On the other hand, the implant is a biomedical medical device that is implanted in vivo and exerts its desired function. The implant is manufactured using a biocompatible material that is very stable with respect to biological tissues so that it has no side effects and does not cause chemical and biochemical reactions. Once the soft tissue is intervened between the bone and the implant, the bone-binding force of the bone must be increased by filling only the complete bone. In addition, the implant should not be deformed or destroyed even under repeated loads and instantaneous pressures, so the material should be made of a material with very high mechanical strength.

In order to satisfy such conditions, various metals and alloys have been developed as suitable materials for implants. However, if the metal implant is implanted in vivo and then put in the body for a long time, the metal ion of the metal implant is eluted by the tissue fluid or the body fluid in the body, and the metal ion of the metal implant is eluted by contacting or rubbing the metal implant in vivo. Elution of these metal ions causes the implant to corrode, react with macrophage of the living body, and cause inflammatory cells or giant cells. For the same reason, the problem that the metal implant cannot satisfy the biocompatibility, chemical compatibility and mechanical compatibility, which are the conditions to be provided as a biomaterial. Therefore, in order to solve this problem, various kinds of bio ceramics and the like have been developed, but most ceramics are weak in impact and difficult to process, and thus cannot be used alone in implant production.

Among the most implant materials currently used are biocompatible titanium (Ti) metals and titanium alloys. Titanium is not only easy to process, but also relatively lighter than other metals, and can be made of alloys of other metals or improved in strength if appropriately processed.

Recently, the surface of titanium implants is coated with bio-compatible calcium phosphates-based ceramic hydroxyapatite (hereinafter abbreviated as "HA") to prevent the implantation of metal ions and prevent bio-affinity. Implants with mechanical strength have been developed and applied in orthopedic or dental applications. Plasma spraying is most commonly used as a method of coating HA on implants. The plasma spraying method is mainly used for coating ceramic materials having a relatively solid solution point to easily perform a large amount of coating work at once. The HA powder is formed by melting the HA powder with a flame and spraying the implant.

Due to the excellent biocompatibility of HA ceramics, the HA coated implants adapt quickly to the bone and have high adhesion to the bone around the implant. In addition, HA implants have a short treatment duration, do not require accurate procedures, and do not cause problems such as physiological and immunological stability that can occur in metal implants when used for a long time. Therefore, it was expected that the HA ceramic coated composite metal implant could be used to solve the problems that may be present in the doctor and the patient at the same time.

However, HA implants are exposed to high temperatures during the coating process, forming HA coating layers that are not chemically uniform, and degrading or absorbing after prolonged in vivo. In addition, the HA coating layer of the existing implant coated with HA is only 6.7 ± 1.5 MPa adhesion of the implant is not suitable for use as an implant having a strong and dense coating layer required in orthopedic or dental.

As described above, existing implants coated with HA have been reported to have problems such as low crystal uniformity of the coating layer, weak adhesion with metal implants, and degradation or absorption in vivo. That is, the adhesion between the HA coating layer and the bone of the existing implant is good, but the HA coating layer is dissolved in vivo, and there is a problem in that a phenomenon in which the HA coating layer is separated from the surface of the metal implant is separated. Since the HA coating layer is not absorbed by osteoclasts in vivo, it can not induce bone remodeling, and the implant is isolated from the new bone. Thus, existing HA implants have excellent initial reactivity but have been found to be inadequate for long term clinical applications.

Accordingly, the present inventors have endeavored to develop a method for forming a thin film coating layer having strong adhesion and uniform crystals on a metal implant on the metal implant. As a result, the ultra-slim coating of the metal implant with a supersaturated calcium phosphate solution using calcium salts and phosphate salts results in a biometric coating. The present invention was completed by developing a calcium-phosphorus implant having excellent suitability and confirming that the calcium phosphate ultra-thin coating layer of the calcium-phosphorus implant quickly induced new bone formation.

It is an object of the present invention to provide an implant having excellent biocompatibility and new bone formation ability on the surface of a metal implant and excellent bone bonding ability with biological bone.

1 is a photomicrograph of the surface of the calcium phosphate ultra-thin coated calcium-phosphorus implant of the present invention,

2 is a photograph of the surface of the uncoated implant under a microscope,

3 is a bottom surface photograph of the calcium phosphate ultra thin coated calcium-phosphorus implant of the present invention,

4 is a top surface photograph of the calcium phosphate ultra thin coated calcium-phosphorus implant of the present invention,

5 is a surface photograph of the calcium phosphate ultra thin coated calcium-phosphorus implant of the present invention.

In order to achieve the above object, the present invention provides an ultra-thin coating calcium-phosphorus implant with a supersaturated calcium phosphate solution using calcium salts and phosphate salts on metal implants.

The calcium phosphate ultra-thin coated calcium-phosphorus implant of the present invention can be used as a biomedical medical device for dental, trauma, orthopedic, maxillofacial and mandibular surgery and surgery.

The material of the implant used in the present invention is easy to process with titanium and relatively light compared to other metals, and is made of an alloy with other metals or through an appropriate treatment process, the mechanical strength is greatly improved. In particular, it forms a very dense and highly reformable passivated oxide film in the air or in water and has a very large corrosion resistance, and has a great advantage of having a close bond of bone and osteointergration when embedded in bone. It is most commonly used as an implant material.

The present inventors performed the calcium phosphate ultra-thin coating on the titanium implant in the following manner.

First, the supersaturated calcium phosphate solution was prepared according to the method described in the existing patent application (Korean Patent No. 10-1999-038528) of the present inventors, and ultrathin coating was performed on the dental titanium implant using the same.

Calcium phosphate ultra thin coating method used in the present invention

1) dissolving calcium phosphate crystals or calcium salts and phosphate salts in an acid solution to prepare a high concentration of calcium ions and phosphate ion solutions (step 1);

2) preparing a mixed solution by mixing the high concentration of calcium and phosphate ion solutions with an alkaline solution at a low temperature (step 2);

3) preparing a calcium phosphate ultra-thin coating solution by removing amorhpous calcium phosphate particles or crystals which may act as nuclei of precipitation and crystal growth from the mixed solution (step 3); And

4) applying the calcium phosphate ultra thin coating solution to the implant to form a calcium phosphate ultra thin film (step 4).

Specifically describing step 1, any kind of calcium salt and phosphate salt may be used for the preparation of the supersaturated calcium phosphate solution. In the present invention, any kind of calcium phosphate crystal can be used. The calcium phosphate crystal used in the present invention may be one obtained by an artificial synthesis method known in the art. For example, as known from C. Rey et al ., Calcif. Tissue Int ., 45, 157-164, 1989; Calcif. Tissue Int ., 46, 157-164, 1990, Ca (NO ₃ ). _2, the solution and the (NH ₄₎ apatite either by mixing a solution of the 2HPO ₄ and ammonia solution in distilled water, rapidly filtered, and freeze-dried or using CaCl ₂ · 2H ₂ O and KH ₂ PO ₄ was dissolved in distilled water 4H ₂ O You can also get

Apatite crystals used in the present invention may also be isolated from bone tissue (Kim, HM et al., J. Bone Miner. Res ., 10, 1589-1601, 1995). In the case of using artificially synthesized calcium phosphate crystals, there is an advantage that the kind of ions contained in the solution can be limited to only ions constituting the crystals such as calcium ions, phosphate ions, and carbonate ions. In addition, a solution prepared by demineralizing calcified tissue with an acid solution may be used immediately in step 2. The acid solution used to dissolve the calcium phosphate crystal may be prepared using any kind of acid. For example, N- [2-hydroxyethyl] piperazine-N '-[2-ethanesulfonic acid] (N- [2-hydroxyethyl] piperazine-N'-[2'-ethanesulfonic acid]), N- N-tris- [hydroxymethyl] methyl-2-aminoethanesulfonic acid, 1,4-piperazindiethanesulfonic acid

(1,4-piperazinediethanesulfonic acid), (3-N-morpholino) propanesulfonic acid ((2-N-morpholino) propanesulfonic acid), conventional organic acids such as acetic acid, HCl, HBr, HI, H ₂ SO ₄ , Inorganic acids such as H ₃ PO ₄ , HNO ₃ , H ₂ CO ₃ or mixtures thereof can be used. Preferably, HCl and N- [2-hydroxyethyl] piperazine-N '-[2-ethanesulfonic acid] are used. Calcium phosphate crystals are dissolved above the concentration at which the formation of crystal precipitates is possible in solution mixed with the alkaline solution.

Specifically describing step 2, homogeneous nucleation of calcium phosphate in solution is inhibited due to the low temperature, and thus free ions are not lost, and thus can be used for formation of a thin film of calcium phosphate. In addition, the use of an appropriate buffer system can further enhance this inhibitory effect.

Specifically describing step 3, in order to precipitate intangible calcium phosphate granules, an alkaline solution is added to an acid solution in which calcium phosphate is dissolved. At this time, in order to suppress the precipitation reaction of calcium phosphate in the solution to maintain free ions at a high concentration, the temperature of the two solutions and the reaction temperature should be kept low. It is preferable to make temperature 0-37 degreeC preferably.

To prepare the alkaline solution, conventional inorganic bases such as NaOH, KOH, LiOH, Ca (OH) ₂ , Mg (OH) ₂ , NH ₄ OH, tris [hydroxymethyl] aminomethane (tirs [hydroxy-

methyl] aminomethane), bis [2-hydroxyethyl] iminotris [hydromethyl] methane (bis [2-

organic bases such as hydroxyethyl] aminotris [hydroxymethyl] methane), 1,3-bis [tris (hydroxymethyl) methylamino] propane, or mixtures thereof. Can be. At this time, the organic base is selected in consideration of the buffer tolerance of each base according to the desired pH range. In addition, the temperature at which the supersaturated calcium phosphate ion solution can be prepared becomes a boundary when using an organic base than when using an inorganic base.

In addition, the alkali solution is added so that the pH of the entire mixed solution is 6.0 to 8.0, more preferably so that the pH is 7.0 to 7.6. Calcium phosphate crystals vary in their crystallographic properties depending on pH. Therefore, the desired kind of crystal can be obtained by adjusting pH. The supersaturated solution of ions for preparing dicalcium phosphate dihydrate crystals has a pH of 6.0 to 6.5, a pH of 6.5 to 6.8 for preparing octacalcium phosphate crystals, and a biomaterial. In order to manufacture the apatite crystal film which is widely used as a pH, the pH is adjusted to 6.8 to 8.0.

In order to form apatite membrane with a uniform surface using the solution, the intangible calcium phosphate granules formed in the solution must be removed. Intangible calcium phosphate granules contained in the solution neutralized with alkaline solution are removed by commonly used filtration or centrifugation. When the filtration method using the filter is performed, microbes in the solution can be removed at the same time, so that there is no need to sterilize separately later.

The ion concentration of the supersaturated calcium phosphate solution used in the present invention is 6.0 to 30.0 mM ² [Ca ²⁺ ] x [HPO ₄ ^2- ] depending on the reaction conditions. The ion concentration in the supersaturated calcium phosphate solution is high enough to form a precipitate by homogeneous nucleation, but the formation of precipitates or crystals is suppressed by lowering the temperature in the preparation step. However, contacting a supersaturated calcium phosphate solution with a solid surface allows crystals to form, adhere to, and grow on the surface by heterogeneous nucleation, which is not affected by this nucleation inhibitory action. Since the concentration of free ions in the calcium phosphate solution used in the present invention is very high, crystals can be easily formed by heterogeneous nucleation even at low temperatures, and heterogeneous nucleation even under conditions requiring high energy, such as in a surface state with a small charge amount. Crystals can be easily formed by

Referring to step 4 specifically, it is preferable that the temperature at the time of forming a thin film is 0-60 degreeC. More preferably, the temperature is 0 to 37 DEG C in the initial stage of crystal formation on the solid surface, and 0 to 60 DEG C in the step of proliferating and maturing the crystal. In addition, the reaction time of the initial stage of the crystal formation is 1 to 6 days and the reaction time of the growth and maturation of the crystal is preferably 5 to 24 hours, but the reaction time may vary depending on the material of the implant used.

The calcium phosphate ultra thin film formed on the implant surface by the above-mentioned calcium phosphate ultra thin coating method is apatite crystal thin film having a thickness of 20 to 50 nm, uniform crystal size, and stable structure, and has a low crystallinity similar to that of bone apatite in vivo. Due to its excellent reactivity and its extremely small crystal size, the reaction surface area is wide, which increases the surface reactivity of apatite crystals, allowing interaction in a cellular or organic environment (see FIG. 1 ). Therefore, the calcium-phosphorus implant of the present invention is coated with a calcium phosphate ultra thin film having the above characteristics and has excellent biocompatibility.

The present inventors, after implanting the calcium-phosphorus implant of the present invention coated with calcium phosphate ultra thin film in vivo and analyzed the bone binding force with the living bone, the calcium-phosphorus implant of the present invention has excellent binding force with the surrounding bone in vivo. And it was found. In addition, as a result of confirming the tissue response in vivo, it was possible to obtain a significantly better implant-bone interface than the conventional non-coated implant, which coated calcium phosphate attracts osteoblasts and progenitor cells in bone tissue to the implant surface It means that you have the ability to induce. In addition, the inventors confirmed that the calcium-phosphate implant surface of the present invention coated with calcium phosphate ultra thin film was fairly uniform compared to the surface of the non-coated implant, and the lower portion, upper portion, and entire portion of the calcium phosphate ultra thin film coated implant fixture. to obtain a surface picture (Figs. 15).

Hereinafter, the present invention will be described in detail by way of examples.

However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.

Example 1 Preparation of Calcium Phosphate Ultra Thin Coatings

<1-1> Preparation of Supersaturated Calcium Phosphate Solution

In order to apply calcium phosphate ultra-thin coating on dental titanium implants, the inventors prepared the supersaturated calcium phosphate solution as follows.

Rapid mixing of calcium ion solution in which 17.7 mg of Ca (NO ₃ ) ₂ 4H ₂ O was dissolved in 250 ml of distilled water and phosphate ion solution in which 40 mg of (NH ₄ ) ₂ · HPO ₄ and 1 ml of ammonia water were dissolved in 500 ml of distilled water After filtration and freeze-drying, apatite crystals were synthesized. 400 mg of apatite crystals were dissolved in 40 ml of 0.2 M HCl to prepare an acidic ion solution containing calcium ions and phosphate ions. The acidic ionic solution was diluted with a 0.2 M HCl solution to prepare a solution having a concentration of 15% calcium phosphate, and then mixed with the 0.2 N NaOH solution and stirred to prepare an ionic solution of pH 7.4. The temperature of all the solutions above was kept at 4 ° C. At this time, intangible calcium phosphate was rapidly formed, but because the temperature was lowered, free ions that did not participate in the formation of the intangible calcium phosphate granules remained, and the amount of precipitated crystals gradually decreased to equilibrium. After leaving the ionic solution at 4 ° C. for 10 minutes, a neutralized ionic buffer solution was prepared by removing the produced calcium phosphate using a 0.2 μm filter.

The buffer solution was measured by atomic absorption spectrophotometry (Perkin Elmer, USA) and colorimetric method (Bartlett, GD et al., J. Biol . Chem., 234, 466-468, 1959). As a result, it was confirmed that a supersaturated solution was prepared with an ion concentration of 15 to 20 mM ² [Ca ²⁺ ] X [HPO ₄ ²⁻ ]. The supersaturated solution thus obtained was stored at 4 ° C. until use.

<1-2> calcium phosphate ultra thin coating

Calcium phosphate ultrathin coating was performed on the dental titanium implant using the supersaturated solution prepared in Example <1-1>.

First, a dental titanium implant MAT implant (machined surface Avana-typetitanium, AVANA. Co.) is placed in a container made to coat about 20 implants at a time and 150 to 200 ml of the supersaturated solution is added thereto. It was coated for 1-6 days in a thermostat maintained at 8 ° C. The temperature was then raised to 37 ° C. and further coated at this temperature for 5 to 24 hours. The whole process of coating was carried out while maintaining a low temperature in a clean room, and after the coating was finished, it was repeatedly washed at least once with distilled water, dried at least 1 hour in a cleanbench, and then radiated at Greenpia. Sterilized by (γ-ray).

As described above, the surface of the lower portion, the upper portion, and the whole of the fixture of the calcium phosphate ultra thin coating dental implant was obtained ( FIGS. 3 to 5 ). In addition, the calcium phosphate ultra-thin coated and uncoated implants of the present invention were observed under a scanning electron microscope (SEM: 840A, JEOL, Japan) and a SEM photograph with a magnification of 10,000 times was obtained. As can be seen in the SEM image, the surface of the implant without coating the calcium phosphate ultra-thin film was large and uneven in crystal size and had a narrow reaction surface area ( FIG. 2 ). On the other hand, the ultra-thin calcium phosphate film coated on the calcium-phosphorus implant of the present invention had an extremely small and uniform crystal size and a stable structure with a wide reaction surface area ( FIG. 1 ).

Experimental Example 1 Measurement of In Vivo Bone Binding Force of Calcium Phosphate Ultra Thin Coated Calcium Phosphorus Implants

In order to compare the bone binding force of the calcium-phosphorus implant of the present invention coated with calcium phosphate ultra thin film with the bone binding force of the existing implant, the present inventors compared the calcium-phosphorus implant prepared in Example <1-2> with a conventional MAT implant The bone binding force between the implant and the living bone was measured in vivo using an edible medical device.

First, the animals used in the experiment were systemically healthy xylazine hydrochloride (Xyla-) in beagle dogs weighing about 15 kg, aged 13 to 16 months of age.

1.2 to 1.4 ml (1 ml = 23.5 mg) of zine hydrochloride, rompun (BAYER) was injected and 1.0 to 1.2 ml (1 ml = 50 mg) of ketamine hydrochloride was injected, followed by endotracheal intubation. Internal diameter 7.0 mm). Angiocatheter was inserted into the vein of the experimental animal and ventilation was controlled by inhaling 1.0 to 1.5% of N2O-O2-Enflurane through an endotracheal tube with a ventilator. Respiratory rate: 150-200 mL, frequency: 14-15 times / minute), and muscle relaxant was not administered. The sap was supplied by injecting a Hartman seed solution at a rate of 100 to 200 ml / hour into the ventilation-controlled experimental animal as described above, and it was confirmed that the heart rate was 55 to 60 times / min by intermittently measuring the armpit. In addition, when there is a sudden movement during the operation of the experimental animals, 25 mg of thiopental or 50 mg of ketamine was injected intravenously.

In the right femur of 8 beagle dogs prepared in the same manner as above, two calcium-phosphorous implants (4.0 mm X 8.5 mm, diameter X length) of Example <1-2 were implanted per animal by a standard surgical method, and the left femur was placed on the right femur. Existing MAT implants (4.0 mm x 8.5 mm, diameter X length) were implanted and a total of 32 implants were implanted in 8 beagle dogs.

After 28, 56, 84, and 168 days of implant placement, two beagle dogs were generally anaesthetized, and then, using a torque driver (Torque driver, Tohnici FTD2-S, Tokyo, Japan), Bone binding force was measured. As a result, it was confirmed that the implant of the present invention coated with calcium phosphate ultra-thin film is a biocompatible biomedical medical device having superior bone bonding ability than the conventional implant.

Experimental Example 2 Histological and Histological Response Test of Calcium Phosphate Ultra Thin Coated Calcium Phosphorus Implant with Biological Tissue

In order to measure the histological and histometric response of the calcium-phosphorus implant prepared in Example <1-2> with biological tissues, the inventors conducted the following experiment.

After 3, 7, 14, 28, and 168 days after the same surgical procedure and implant implantation as in Experimental Example 1, a single beagle dog was sacrificed by general anesthesia, and a specimen was prepared. The bone fusion to the implant without the intervention of soft tissue was confirmed by bone-to metal contact.

First, in order to secure tissue specimens, bone fragments containing implants were taken and fixed with 10% neutral buffered formalin to prepare tissue specimens, and alcohol concentrations (70%, 80%, 95%, 95% at 24 hour intervals) were obtained. 100%, 100% and 100% pure alcohol) was gradually dehydrated while gradually increasing the tissue specimen. 100% alcohol and acetone were exchanged in a 2: 1, 1: 1 and 1: 2 ratio to replace the dehydrated tissue, and spur resin (manufacturer's description) was prepared according to the manufacturer's instructions, followed by acetone and spur Resin was exchanged in the ratio of 2: 1, 1: 1, 1: 2 to infiltrate the dehydrated tissues, at which time 100% spur resin was exchanged twice at intervals of 24 hours. The infiltrated tissue was placed in the template to be embedded and polymerized at room temperature for 24 hours and then polymerized in a 70 ° C. heater for 8 hours. Tissue specimens separated from the mold along the long axis of the implant were cut to a thickness of 150 μm using a low speed diamond saw (Excel, Extec, USA) in and out of the femur. The cut tissue specimen was attached to a plastic slide and polished as thin as possible to a final thickness of about 20-30 μm using a multi-step grinding system, followed by toluidine blue for histological analysis. Stained with.

The stained tissue specimens were observed with an optical microscope to compare the degree of adhesion between implanted implants and bone interface, and the formation and adhesion of new bone between the implant and host bone was observed. Was measured. At this time, histomorphometry was input to the computer using a microscope attached to the CCD camera and calculated as a percentage using an image analysis program (Imagepro-Plus V. 3.02).

As a result, the calcium-phosphorus implant of the present invention had a higher degree of adhesion between the bone interface and the new bone formation ability and the adhesion state between the implant and the host bone, compared with the existing MAT implant, and the degree of adhesion at the implant surface was also increased. It was.

Therefore, it was confirmed that the calcium-phosphorus implant of the present invention is excellent in bone adhesion ability and new bone formation ability, and thus can be usefully used as a biomedical medical device.

The calcium phosphate ultra thin coated calcium-phosphorus implant of the present invention is coated with calcium phosphate having excellent bioreactivity, a wide reaction surface area, and uniform crystals, so that the peripheral bone can be rapidly adapted to the implant and the coating layer Excellent adhesion to implants and high bone bonding ability with living bones can be useful as a biomedical instrument for dental surgery, trauma, orthopedic, maxillofacial and mandibular surgery and veterinary surgery.

Claims (10)

Calcium phosphate (Ca-P implant) coated with calcium phosphate thin film with a thickness of 20-50 nm. delete The method of claim 1, 1) dissolving calcium phosphate crystals or calcium salts and phosphate salts in an acid solution to prepare a high concentration of calcium ions and phosphate ion solutions (step 1); 2) preparing a mixed solution by mixing the high concentration of calcium and phosphate ion solutions with an alkali solution at a low temperature (step 2); 3) preparing a calcium phosphate ultra-thin coating solution by removing amorhpous calcium phosphate particles or crystals which may act as nuclei of precipitation and crystal growth from the mixed solution (step 3); And 4) Calcium-phosphorus implant, characterized in that produced by the method comprising the step of forming a calcium phosphate ultra-thin film on the implant surface by applying the calcium phosphate ultra-thin coating solution to the implant (step 4). 4. The calcium-phosphorous implant according to claim 3, wherein the temperature of the acid solution and the alkali solution and the reaction temperature of step 2 are 0 to 37 ° C. 4. The acid solution of claim 3 wherein the acid solution of step 1 is an inorganic acid, N- [2-hydroxyethyl] piperazine, selected from the group consisting of HCl, HBr, HI, H ₂ SO ₄ , HNO ₃ and H ₂ CO ₃ -N '-[2-ethanesulfonic acid] (N- [2-hydroxyethyl] piperazine-N'-[2'-ethanesulfonic acid]), N-tris- [hydroxymethyl] methyl-2-aminoethanesulfonic acid (N-tris- [hydroxymethyl] methyl-2-aminoethanesulfonic acid), 1,4-piperazinediethane-sulfonic acid, (3-N-morpholino) propanesulfonic acid ( (2-N-morpholino) propanesulfonic acid) A calcium-phosphorus implant characterized by using an organic acid selected from the group consisting of acetic acid or mixtures thereof. 4. The tris [hydroxyl methyl] amino according to claim 3, wherein the alkaline solution of step 2 is selected from the group consisting of NaOH, KOH, LiOH, Ca (OH) ₂ , Mg (OH) ₂ , NH ₄ OH. Methane (tirs [hydroxy-methyl] aminomethane), bis [2-hydroxyethyl] iminotris [hydromethyl] methane (bis [2-hydroxyethyl] aminotris [hydroxymethyl] methane), 1,3-bis [Tris (hydroxymethyl) methylamino] propane (1,3-bis [tris (hydroxymethyl) methylamino Calcium-phosphorus implant, characterized in using an organic base selected from the group consisting of propane) or mixtures thereof. 4. The calcium-phosphorous implant according to claim 3, wherein the pH of the solution is adjusted to 6.0 to 8.0 by adding an alkaline solution in step 2. 4. The calcium-phosphorous implant according to claim 3, wherein the intangible calcium phosphate granules or crystals in step 3 are removed by filtration or centrifugation using a porous filter. 2. The calcium-phosphorus implant according to claim 1 as a biomedical medical device for healing bone defect tissue. 10. The calcium-phosphorus implant according to claim 9, wherein the biomedical medical instrument is used for dental surgery, trauma, orthopedic surgery, maxillofacial and maxillofacial surgery, and veterinary surgery.