WO2007061001A1 - Complex of gel carrier and hydroxyapatite and process for producing the same - Google Patents

Abstract

A process for producing a complex that excels in the efficiency of hydroxyapatite formation and realizes formation of hydroxyapatite within a substrate. A gel carrier is disposed between an anode and a cathode. A solution containing calcium ions is used as an anode-side migration solution, and a solution containing phosphate ions as a cathode-side migration solution. Electrophoresis is carried out by current passage so as to form hydroxyapatite within the gel carrier, thereby producing a complex of gel carrier and hydroxyapatite.

Description

 Composite of gel carrier and hydroxyapatite and method for producing the same Technical Field

 The present invention relates to a composite of a gel carrier and hydroxyapatite and a method for producing the same.

 Background art

 [0002] Since nodoxyapatite is very similar to the components of bones and teeth, a complex in which hydroxyapatite is held on a base material such as an organic polymer material is used as an artificial bone or a human tooth root. Attempts have been made to use it as a forming material.

[0003] Then, as a method for producing such a composite, the present inventors have alternately immersed the substrate in a solution containing calcium ions and a solution containing phosphate ions, thereby Report the method of forming hydroxyapatite on the surface of the material (hereinafter referred to as “alternative dipping method”)!

 Patent Document 1: International Publication W099Z58447 Pamphlet

 Patent Document 2: JP 2000-327313 A

 Patent Document 3: Japanese Patent Laid-Open No. 2000-327314

 Patent Document 4: Japanese Unexamined Patent Application Publication No. 2004-026653

 Patent Document 5: Japanese Unexamined Patent Application Publication No. 2004-081739

 Disclosure of the invention

 Problems to be solved by the invention

[0004] However, with this alternate dipping method, although hydroxyapatite can be formed on the surface of the substrate, it has been difficult to form hydroxyapatite sufficiently and evenly inside. In addition, since it takes time to form practically sufficient hydroxyapatite on the substrate, further improvement in the formation rate of hydroxyapatite is required.

[0005] Therefore, the present invention provides a method for producing a composite that is excellent in the formation efficiency of hydroxyapatite and enables the formation of hydroxyapatite inside the substrate, and the composite produced thereby. For the purpose of provision.

 Means for solving the problem

 [0006] In order to achieve the above object, the present invention provides a method for producing a composite of a gel carrier and hydroxyapatite, wherein the gel carrier is disposed between the anode and the cathode, and the electrophoretic solution on the anode side is obtained. Using a solution containing calcium ions and a solution containing phosphate ions as an electrophoretic solution on the cathode side, and carrying out electrophoresis by energization to form hydroxyapatite in the gel carrier. And

 The invention's effect

 [0007] According to the present invention, a solution containing calcium ions is used as the electrophoretic solution on the anode side, and a solution containing phosphate ions is used as the electrophoretic solution on the cathode side. Uniform hydroxyapatite can be formed, and the formation speed can be improved. For this reason, it becomes possible to supply a complex in which hydroxyapatite is held on a gel carrier as a material for forming an artificial bone or an artificial tooth root more easily.

 Brief Description of Drawings

 1 is a conceptual diagram of electrophoresis in an embodiment of the present invention, and FIG. 1 is a diagram showing an example of a reaction for forming hydroxyapatite.

 FIG. 2 is a photograph showing an electrophoresis apparatus in one example of the present invention.

 FIG. 3 is a photograph of the appearance of an agarose gel in the Example of the present invention.

 FIG. 4 is an SEM photograph of the agarose gel in the example of the present invention, in which (a) is a non-turbid region (X 3000) on the anode side of the agarose gel, and (b) is a cathode of the agarose gel. Side cloudiness regions (X1500) and (c) are SEM photographs in which the magnification of the cloudiness region (X15000) is changed.

 [FIG. 5] FIG. 5 is a SEM photograph of the agarose gel in the Example of the present invention, (A) is a SEM photograph of the central part of the cloudy area, and (B) is a SEM photograph of the surface part of the cloudy area. It is.

FIG. 6 is a graph showing the results of XRD analysis of the nodoxyapatite formed in the Example of the present invention. FIG. 7A is a schematic view showing an example of an electrophoresis apparatus used in the production method of the present invention.

 FIG. 7B is a schematic diagram showing another example of the electrophoresis apparatus used in the production method of the present invention.

 BEST MODE FOR CARRYING OUT THE INVENTION

 [0009] The electrophoretic solution on the anode side only needs to contain calcium ions. For example, a solution containing a calcium compound (calcium salt) such as calcium chloride, calcium acetate, or calcium nitrate is preferable. As the solvent of the solution, for example, an aqueous solvent such as water or a buffer solution is preferable, and a buffer solution capable of adjusting pH is particularly preferable. As the buffer, for example, a Tris buffer such as Tris-HCl buffer can be used. Each of the calcium compounds and solvents can be one type! /, Or two or more types can be used together!

 [0010] The concentration of calcium ions in the anodic electrophoretic solution is not particularly limited !, but is, for example, 10 to 200 mmol ZL, preferably 10 to 160 mmol ZL, and more preferably 10 to 40 mmol ZL. The density of hydroxyapatite formed inside the gel carrier can be adjusted by, for example, the calcium ion concentration and the phosphate ion concentration of the cathode side electrophoresis solution described later. In addition, since this anodic electrophoretic solution can sufficiently suppress a decrease in the formation rate of hydrated xybate, the concentration of phosphate ion that preferably contains substantially no phosphate ion is, for example, lOmmolZL or less. Preferably, it is below the measurement limit (for example, OmmolZL).

 [0011] The pH of the anodic electrophoretic solution is, for example, 4.6 to 9.2, preferably 5.8 to 8, and more preferably 6.6 to 7.4. It can be adjusted appropriately by using a buffer solution such as

The electrophoretic solution on the cathode side contains phosphate ions, and for example, sodium hydrogen phosphate, sodium dihydrogen phosphate, ammonium dihydrogen phosphate, ammonium dihydrogen phosphate A solution containing a phosphate compound such as hum is preferred. As the solvent of the solution, for example, an aqueous solvent such as water or a buffer solution is preferable. As the buffer, for example, Tris buffer such as Tris-HCl buffer, phosphate buffer, etc. can be used, and the concentration thereof is, for example, 10 to 200 mmo 1 ZL, preferably 10 to 160 mmol ZL, and more. Preferably 10-40mmolZL It is. Either one type of phosphoric acid compound or solvent may be used, or two or more types may be used in combination.

 [0013] The concentration of phosphate ions in the cathodic electrophoresis solution is not particularly limited !, but is, for example, 10 to 200 mmol ZL, preferably 10 to 160 mmol ZL, and more preferably 10 to 40 mmol ZL. The pH of the electrophoresis solution is not particularly limited, but is, for example, 5.8 to 8, preferably 6.6 to 8, more preferably 7.4 to 8, for example, the buffer solution as described above. Can be adjusted as appropriate. In addition, since this cathodic migration solution can sufficiently suppress the decrease in the formation rate of hydroxyapatite, the concentration of calcium ions that preferably contains substantially no calcium ions is, for example, lOmmolZL or less. Preferably, it is below the measurement limit (for example, OmmolZL).

 [0014] The combination of the calcium compound contained in the anodic electrophoretic solution and the phosphate compound contained in the cathodic electrophoretic solution is not particularly limited. For example, a combination of calcium chloride and sodium hydrogen phosphate, acetic acid A combination of calcium and ammonium dihydrogen phosphate is exemplified. The ratio of the calcium ion concentration of the anodic electrophoretic solution to the phosphate ion concentration of the cathodic electrophoretic solution is, for example, in the range of 3: 5 to 5: 3, preferably 5: 5 to 5: The range of 3. These electrophoretic solutions may contain other ions, for example, as long as the formation of hydroxyapatite is not impaired.

[0015] The type of the gel carrier in the present invention is not particularly limited. For example, the gel carrier is substantially insoluble in the above-described electrophoresis solution. Gels that can move acid ions are preferred. An example of such a gel is Hyde Mouth Gel. Hyde mouth gel generally means a gel in water (aqueous solvent). The material of the hide-mouthed gel is not particularly limited as long as it is a substance that gels (swells). For example, it may be a substance that gels by heating and cooling a mixed solution with an aqueous solvent, or a hydrogen bond. A substance that gels due to, for example, a substance that gels by an additive such as an aggregating agent, a crosslinking agent, or a polymerizing agent may be used. The material of the gel carrier may contain an ionic group, but is preferably nonionic. In addition, when the produced gel carrier-hydroxyapatite complex is used in vivo, the gel carrier is preferably biocompatible. [0016] Examples of such materials include agarose, hyaluronic acid, alginic acid, pullulan, pectin, starch, mannan, chitin, chitosan, chitosan-chitin copolymer, dextran, dextran sulfate, and pregelatinized starch. Examples include polysaccharides such as starch, cellulose, and cellulose derivatives (such as methoxycellulose, ethoxycellulose, propoxycellulose, and hydroxyethylcellulose). Also, fibronectin, fib mouth-in, sericin, atelocollagen, collagen, gelatinized collagen, gelatin, casein, polyspartate, polyglutamate, poly-gamma-glutamic acid, polylysine and other proteins, polypeptides or polyamino acids; lignin , Polyortune, poly (oral taxane), poly (ethylene succinate), poly (bull alcohol), poly (bullyl pyrrolidone), polyethylene glycol, poly (acrylamide), poly (hydroxyethyl) methacrylate, darcosilethyl methacrylate (GEMA), partial sulfate Examples thereof include organic polymer gels obtained by crosslinking polymers such as GEMA. In addition, hydrophilic rosin partially crosslinked with polybulualcohol, polyacrylamide, polybylpyrrolidone or the like can be used. The cross-linked polybulal alcohol can be obtained, for example, by partially bridging polybulal alcohol with a bifunctional aldehyde such as dartalaldehyde. These materials may be natural products, semi-synthetic products, or synthetic products. Among these, agarose, hyaluronic acid, collagen and the like are preferable because they are excellent in human safety and degradability. In addition, these materials can be either one type, or two or more types can be used in combination.

[0017] The method for preparing the gel carrier is not particularly limited, and can be prepared by a conventionally known method according to the type of the forming material. For example, in the case of agarose or gelatin, it can be prepared by dissolving in a solvent by heating, and cooling and solidifying the obtained solution. In the case of polybutyl alcohol, polyamino acid, and the like, for example, they can be prepared by adding a crosslinking agent such as dartalaldehyde to these aqueous solutions and solidifying them. As the solvent, for example, a solution that conducts electricity can be used. Specific examples include aqueous solvents such as aqueous solutions of phosphoric acid and sodium phosphate, aqueous solutions of phosphoric acid such as sodium dihydrogen phosphate, and phosphate buffers, and Tris buffers such as Tris-HCl buffer. An aqueous phosphoric acid solution such as an aqueous solution of disodium hydrogen and sodium dihydrogen phosphate is preferred. Moreover, the density | concentration is 10-4 OmmolZL, for example, Preferably it is 10-20 mmolZL. In the case of a buffer solution, the p H is, for example, 5.8 to 8, preferably 6.6 to 8, and more preferably 6.6 to 7.4.

[0018] The pH of the gel carrier is not particularly limited, but is, for example, 5.8 to 8, preferably 6.6 to 8, and more preferably 6.6 to 7.4. The pH of the gel carrier can be adjusted to a desired value by, for example, the above-mentioned solvent used when producing the gel carrier.

[0019] The content of the forming material in the gel carrier is not particularly limited, and is a force S that can be appropriately determined according to the type of the forming material, for example, 0.5 to: LO wt%, preferably 0. 5 to 5% by weight, more preferably 0.5 to 3% by weight.

[0020] The shape and size of the gel carrier are not limited in any way, and can be appropriately determined according to the shape and size of the electrophoresis apparatus to be used. As a specific example, the length of the gel in the ion movement direction (electrophoresis direction) is, for example, 1 to 20 cm, preferably 3 to 10 cm, more preferably 3 to 6 cm, and the thickness is, for example, 0.1 to 1.5 cm, preferably 0.1 to 1.5 cm, 0.2 to 1.5 cm or younger or higher, 0.1 to Lcm, more preferably higher or lower to 0.2 to Lcm. The width of the gel is not particularly limited, but is, for example, 30 cm or less, preferably 20 cm or less, and more preferably 15 cm or less. The lower limit of the gel width is not particularly limited, and is, for example, 0.1 cm, 1 cm, 3 cm, 5 cm, 8 cm, 10 cm or more. Specific examples of the open shape of the genore include a general slab gel and a rod gel.

Next, an example of the production method of the present invention will be described below, but the present invention is not limited thereto.

[0022] A gel carrier is arranged at a predetermined position of the electrophoresis apparatus. As the electrophoresis apparatus, for example, a conventionally known apparatus can be used, and an anodic electrophoretic solution containing calcium ions at one end of the gel carrier and a cathodic electrophoretic solution containing phosphate ions at the other end can be arranged. For example, the form is not limited at all. For example, an electrophoresis apparatus as shown in FIGS. 7A and 7B may be used. Such an electrophoresis apparatus may be in the same form as a so-called submarine type electrophoresis apparatus generally used for electrophoresis of nucleic acids. That is, the electrophoresis apparatus of FIGS. 7A and 7B includes a main body 1 that constitutes a placement portion for placing the gel carrier 2 and two electrode tanks divided by the placement portion, and electrodes 3, 4 With.

[0023] Subsequently, the electrophoresis solution containing calcium ions is poured into the electrode tank in which the anode is arranged, and the electrophoresis solution containing phosphate ions is poured into the electrode tank in which the cathode is arranged. this At this time, the electrophoresis solution is injected into each electrode tank until one end of the gel carrier comes into contact with the anodic electrophoretic solution and the other end of the gel carrier comes into contact with the cathodic electrophoretic solution. Note that the anodic electrophoretic solution and the cathodic electrophoretic solution are preferably separated by a gel carrier. For example, as shown in FIG. 7A, when the electrode 3 is an anode and the electrode 4 is a cathode, the anodic electrophoretic solution 5 and the cathodic electrophoretic solution 6 can be isolated by the gel carrier 2. Alternatively, as shown in FIG. 7B, the gel carrier 2 may be sandwiched between the gel mounting part and the member 7 using the member 7 to isolate the electrophoresis solutions 5 and 6 from each other. The shape of the member 7 is not particularly limited as long as the electrophoresis solution can be isolated. For example, the shape of the member 7 may be concave as shown in FIG. 7B. The material of the member 7 is not particularly limited, and, for example, a conventionally known resin glass that can be the same as the main body 1 can be applied.

[0024] Hydroxyapatite is then formed inside (and on the surface of) the gel carrier by carrying out electrophoresis with an electric charge. The reason why hydroxyapatite can be formed in the gel carrier by the method of the present invention is presumed to be that calcium ions and phosphate ions are forced to move the gel carrier by energization. For this reason, it is considered that the formation region of hydroxyapatite is not affected by the thickness of the gel carrier, for example.

[0025] The conditions for energization are not particularly limited, but the voltage is, for example, 2 to 500 V, and the current is, for example, 2 to 200 mA. The migration time is not particularly limited, and is, for example, 1 to 60 minutes. In addition, the migration time can be adjusted according to the size of the gel carrier, for example, when the length of the gel in the direction of ion movement is 6 cm, for example, about 10 to 30 minutes, and a uniform nose inside the gel carrier. Idroxyapatite can be formed. The nodoxy oxide formed in the gel can be confirmed, for example, with a scanning electron microscope (SEM) or the like as described later. In addition, when hydroxyapatite is formed, the hydroxyapatite formation region in the gel carrier becomes cloudy, and thus, for example, the energization can be terminated by visual confirmation. Hydroxyapatite formed inside (and on the surface of) the gel carrier is preferably a crystal particle, and its particle size is not particularly limited, but is preferably 0.2 to 2 / ζ πι, for example. It is between 0.5 and 111, and preferably between 1.0 and 1. According to the production method of the present invention, it is possible to accelerate the formation rate of hydroxyapatite, for example, about 100 times as compared with the conventional alternate dipping method. [0026] The density of hydroxyapatite in the composite can be adjusted by, for example, the force ion concentration and phosphate ion concentration in each electrophoresis solution, but practically, it is 0.1 wt% or more per equilibrium swelling volume (cm ³ ). More preferably, it is 1 to 25% by weight, particularly preferably 10 to 25% by weight.

 [0027] The mechanism by which hydroxyapatite is formed on the gel carrier by electrophoresis will be described with reference to FIG. The figure shows a solution containing CaCl as the anodic migration solution, the cathode side

 2

 This is an example of using a solution containing Na HPO as the electrophoresis solution. (A) is a conceptual diagram of electrophoresis.

 twenty four

 (B) is a figure which shows the outline of the formation reaction of a hydroxyapatite. As shown in (a) of the figure, a solution containing CaCl on the anode side and a solution containing Na HPO as the cathode side running solution are used.

 2 2 4

 When each is used, as shown in Fig. 2 (b), the calcium ions and phosphate ions generated by energization move to the cathode side and the anode side, respectively, inside the gel. Then, both ions react inside the Hyde mouth gel to form hydroxyapatite.

 [0028] In this way, a composite in which gnoidylapatite is supported on a gel carrier can be produced. Therefore, as another embodiment, the present invention includes a gel carrier-hydroxyapatite composite produced by the production method of the present invention described above. The obtained composite of the present invention has a good hemostatic effect and can be used as a medical material such as a material for forming an artificial bone or an artificial tooth root.For example, the composite is embedded around a damaged living bone or tooth. By planting, it exhibits hemostasis and can form artificial bones and artificial roots. This complex can be stored in physiological saline until use, after various sterilization treatments such as γ-ray sterilization, for example. Therefore, the present invention provides a method of treatment using the gel carrier-hydroxyapatite of the present invention and a gel carrier-noid of the present invention in treatment of living bodies, for example, treatment including hemostasis or artificial osteoarthroplasty. It may also include the use of roxyapatite. Furthermore, the present invention provides a book comprising at least one of the above-described electrophoresis apparatus, anode side / cathode side electrophoresis solution, anode side / cathode side electrophoresis solution reagent, gel carrier, gel material powder, and instruction manual. The gel carrier-hydroxyapatite production kit of the invention may be included.

[0029] Also, in the present invention, if a solution containing carbonate ions is used instead of a solution containing phosphate ions as the electrophoretic solution on the cathode side, by performing electrophoresis by energization, Since calcium carbonate is formed in the gel carrier, a complex of the gel carrier and calcium carbonate can also be produced. As the solution containing carbonate ions, for example, a solution containing a carbonate compound (carbonate) such as sodium carbonate or sodium hydrogen carbonate is preferable. Or an aqueous solvent such as a buffer. Moreover, although the carbonate ion concentration of the electrophoresis solution is not particularly limited, it is, for example, 10 to 200 mmol ZL, preferably 10 to 160 mmol ZL, and more preferably 10 to 40 mmol ZL. Moreover, the pH of the electrophoresis solution is, for example, 5.8 to 8, preferably 6.6 to 8, and more preferably 7 to 8.

[0030] Further, according to the present invention, a solution containing sulfate ions instead of a solution containing phosphate ions is used as the electrophoretic solution on the cathode side, and calcium ion is used as the electrophoretic solution on the anode side. If a solution containing cadmium ions is used in place of the solution containing, a cadmium sulfate is formed in the gel carrier by carrying out electrophoresis by energization. Therefore, a composite of the gel carrier and cadmium sulfate Can also be manufactured. As a solution containing sulfite ions, for example, a solution containing cadmium acetate is preferable as a solution containing cadmium ions, which is preferable for a solution containing sodium sulfate. As the solvent of the solution, for example, an aqueous solvent such as water or a buffer solution can be used as described above. The sulfate ion concentration of the electrophoresis solution is not particularly limited, but is, for example, 10 to 200 mmol ZL, preferably 10 to 160 mmol ZL, and more preferably 10 to 40 mmol ZL. The cadmium ion concentration of the electrophoresis solution is not particularly limited, but is, for example, 10 to 200 mmolZL, preferably 10 to 160 mmolZL, and more preferably 10 to 40 mmolZL. Further, the pH of the electrophoretic solution on each of the cathode side and the anode side is, for example, 5.8 to 8, preferably 6.6 to 8, and more preferably 7 to 8.

 Example 1

[0031] First, a 3 weight o / o agarose gel (length 6 cm x width 11 cm x thickness 0.8 mm) was prepared by a conventional method using lOmmolZL Tris-HQ buffer (pH 7.4). The length of the agarose gel is the length in the ion movement direction (electrophoresis direction). Then, as shown in the photograph in FIG. 2, this agarose gel is placed at a predetermined position of a commercially available electrophoresis apparatus (trade name: Mupid minigel electrophoresis tank: manufactured by ADVANCE Co. Ltd), and an anode is inside. 40 mmol / L CaCl aqueous solution was placed in the arranged electrode tank and 40 mmol ZL Tris-HC1 buffer.

 2

 The mixed solution adjusted to pH 7.4 with a solution was poured into an electrode tank having a cathode disposed therein, and 40 mmol ZL Na HPO aqueous solution was respectively injected. And about 30 minutes under the condition of voltage 100V

 twenty four

 Electrophoresis was performed. 20 minutes after the start of electrophoresis, a cloudy band with a width of about 3 cm was observed near the center line of the agarose gel, and the band moved to the cathode side in the following 10 minutes.

[0032] The appearance of the agarose gel after electrophoresis is shown in the photograph of FIG. As shown in the figure, a white turbid band having a length of 3 cm (X width l lcm X thickness 0.8 cm) was formed on the cathode side (region (b) in the figure) of the agarose gel.

 [0033] After washing the agarose gel after electrophoresis with a large amount of distilled water, the non-turbid region on the anode side (region (a) in Fig. 3) and the white turbid region on the cathode side (region (b) in Fig. 3). And each fragment was lyophilized. Each freeze-dried fragment was stained with osmium tetroxide, and the inside of each fragment was confirmed with a scanning electron microscope (SEM). The results are shown in the SEM photograph in FIG. In the figure, (a) is the anode-side non-cloudy region (X 3000) of the agarose gel, (b) is the cathode-side cloudy region (X 1500) of the agarose gel, and (c) is the cloudy region (X 15000). ). As shown in the figure (a), no precipitation was observed in the anode side region of the agarose gel, whereas in the cathode side cloudy region, many precipitations were seen as shown in the figure (b). Was confirmed. In addition, when the magnification was increased and the above-mentioned cloudy region was confirmed, as shown in FIG. 5 (c), fine particles having a spherical shape with a surface covered with acicular crystals and a particle size of about 1.5 m were obtained. confirmed. Because this crystal structure is unique to hydroxyapatite (Zhang, R .; Ma, PXJ Biomed. Mater. Res., 1999, 45, 285-293, Ma, PX; Zhang, RY; Xiao, G. Z .; Franceschi, RJ Biomed. Mater. Res., 2001, 54, 284-293), it is clear that hydroxyapatite was formed in the cloudy band region of agarose gel.

[0034] In addition, the central portion of the white turbid region shown in FIG. 4 (b) (that is, the central portion in any of the migration direction, width direction, and thickness direction in the white turbid region) and the surface portion of the white turbid region (migration direction) And the central part in the width direction) were confirmed by SEM. The result is shown in Fig. 5. Shown in In the figure, (A) is a SEM photograph of the central part and (B) is a surface part. As a result, even in the interior of the agarose gel, which is formed only by the surface portion, it is difficult to form a hyde mouth xiapatite.

Further, X-ray diffraction (X RD) was performed on the hydroxyapatite particles formed in the agarose gel using an X-ray diffraction apparatus (trade name: RINT in Plane ultra X18: manufactured by Rigaku Corporation). The diffraction results are shown in FIG. In the figure, the horizontal axis indicates the angle and the vertical axis indicates the intensity. As shown in the figure, diffraction peaks 25.8 ° (0 02) and 31.7 ° (211) peculiar to nodyl and idroxyapatite were observed. From this result, formation of hydroxyapatite inside the agarose gel was confirmed by electrophoresis. In the case where hydroxyapatite is formed on a 0.8 cm-thick gel carrier as in the present embodiment by the conventional method of alternately immersing the gel carrier in a calcium salt solution and a phosphate solution, Force One cycle of alternate dipping requires 4400 minutes (74 hours). From this, it can be said that according to this example, hydroxyapatite was uniformly formed on the surface and inside of the gel carrier in an extremely short time.

 [0036] It is known that the sizes of the two peaks 25.8 ° (002) and 31.7 ° (211) in XRD diffraction are relatively related to the crystallinity of nodyl and adroxyapatite. As shown in FIG. 6, the nodoxy hydroxyapatite obtained in this example can be said to have low crystallinity because these peaks are low. Since hydroxyapatite is easily decomposed if the crystallinity is low, the hydroxyapatite obtained in the present example is particularly useful for use in vivo where rapid decomposition is desired.

 Industrial applicability

[0037] As described above, according to the present invention, a solution containing calcium ions is used as the electrophoretic solution on the anode side, and a solution containing phosphate ions is used as the electrophoretic solution on the cathode side. In addition, uniform hydroxyapatite can be formed inside the gel carrier, and the formation speed can be improved. For this reason, it becomes possible to more easily supply the composite in which the gel carrier holds the nodyl and the hydroxyapatite as a material for forming an artificial bone or an artificial tooth root.

Claims

 The scope of the claims  [I] A gel carrier is disposed between the anode and the cathode,  Use a solution containing calcium ions as the electrophoretic solution on the anode side, and a solution containing phosphate ions as the electrophoretic solution on the cathode side.  A method for producing a complex of a gel carrier and hydroxyapatite, comprising a step of forming a hydroxyapatite inside the gel carrier by carrying out electrophoresis by energization.  [2] The production method according to claim 1, wherein the anodic electrophoretic solution and the cathodic electrophoretic solution are separated by the gel carrier. [3] The production method according to claim 1, wherein the pH of the carrier gel is in the range of 5.8 to 8. [4] The production method according to claim 1, wherein the pH force of the electrophoretic solution on the anode side is in the range of 4.6 to 9.2. 5. The production method according to claim 1, wherein the material of the carrier gel is agarose. [6] The production method according to claim 1, wherein the concentration of calcium ions in the anodic migration solution is in the range of 10 to 200 mmol / L. [7] Phosphate ion concentration force in the cathodic solution is in the range of 10-200 mmol ZL The manufacturing method according to claim 1. [8] A composite of a gel carrier and hydroxyapatite, which is obtained by the production method according to any one of claims 1 to 7. [9] A composite of a gel carrier and hydroxyapatite,  The hydroxyapatite is a particle having a particle size of about 1.5 μm,  A gel-nodaloxyapatite complex characterized in that the hydroxyapatite particles are uniformly present inside the gel carrier. [10] A composite of a gel carrier and hydroxyapatite,  The gel carrier is a flat plate having a thickness of 0.1 to 3 cm,  A gel-nodoxyapatite composite, wherein the particles of idoxyapatite are uniformly present inside the gel carrier.  [II] The gel-nodoxyapatite complex according to claim 9 or 10, wherein the hydroxyapatite particles have low crystallinity and can be decomposed in vivo.