JP4279514B2 - Granular bone filling material and method for producing the same - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention belongs to a granular bone filling material having a property of creating new bone when filled in or near a bone, and a method for producing the granular bone filling material.
[0002]
[Prior art]
Conventional bone prosthetic materials are used in the field of dentistry or plastic surgery. Bone prosthetic materials are known to have the property of creating new bone when filled in or near bone. In addition, the bone prosthetic material is characterized by excellent affinity for human teeth and bones. Furthermore, the bone grafting material has a characteristic that the pH value is neutral.
[0003]
In a conventional method for producing a bone grafting material, first, a sol is obtained by kneading a chitosan acidic aqueous solution obtained by dissolving chitin / chitosan with an acidic aqueous solution and granular apatite. As the acid used for dissolving chitin / chitosan, one kind of acetic acid, lactic acid, malic acid, citric acid, adipic acid, tartaric acid, malonic acid, stearic acid, succinic acid, maleic acid, aspartic acid, glycine, etc. is used. .
[0004]
Thereafter, the sol is neutralized with an aqueous solution containing the compound. When the neutralized sol is cured in 3 to 60 minutes, a bone grafting material having a pH in the range of 7.0 to 10.0 is obtained. Then, the bone substitute material is dried. The dried bone filling material is a fragile material. Therefore, the bone prosthetic material is returned to the bone prosthetic material having elastic strength such as rubber by absorbing distilled water or physiological saline into the bone prosthetic material.
[0005]
The bone prosthetic material thus produced is freely cut to a desired size according to the size of the affected part of the living body. The bone prosthesis is reconstructed by inserting it between the jaw bone and the gingiva after performing an operation such as periodontal disease.
[0006]
Note that the bone filling material containing apatite is not moved or eliminated. That is, in the bone grafting material, since the sol is gelled, the apatite granules are appropriately dispersed and fixed. Therefore, when the chitin / chitosan is absorbed by the living body, the osteoid matrix is recognized and replaced with bone.
[0007]
The bone prosthetic material thus produced is freely cut to a desired size according to the size of the affected part of the human body. For example, the bone prosthetic material is reconstructed by performing an operation such as periodontal disease and then embedding it between the jaw bone and the gingiva which are the operated parts.
[0008]
[Problems to be solved by the invention]
However, the conventional bone filling material has a problem that since the body fluid is acidic, the neutral bone filling material and the bone do not conform to each other and it takes a long time to be replaced with new bone in the living body.
[0009]
Therefore, an object of the present invention is to provide a granular bone filling material that can promote the formation of bone, and a method for producing the granular bone filling material.
[0010]
[Means for Solving the Problems]
According to the present invention, in the granular bone filling material comprising a grain-shaped central base material and a coating layer covering the surface of the central base material, wherein the central base material and the coating layer are calcium phosphate compounds. The central base material has a neutral pH value, and the coating layer is composed of a plurality of alkali regions in which the pH value is alkali and the pH values of the alkali are different from each other. A bone filling material is obtained.
[0011]
Further, according to the present invention, a granular bone filling material comprising a grain-shaped central base material and a coating layer covering the surface of the central base material, wherein the central base material and the coating layer are calcium phosphate compounds. In the material manufacturing method, the coating layer is formed on the surface of the central base material so that the central base material having a neutral pH value and the multiple alkaline regions having different alkali pH values are formed. And a process for producing a granular bone filling material.
[0012]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, each embodiment in the granular bone filling material according to the present invention will be described. FIG. 1 is a cross-sectional view showing a schematic configuration of the granular bone filling material in the first embodiment.
[0013]
Referring to FIG. 1, the granular bone filling material is a granular material comprising a granular base material 11 and a coating layer (12, 13) having multiple alkali regions on the surface of the central base material 11. It is a bone filling material. The granular bone filling material is a calcium phosphate compound. The central substrate 11 has a neutral pH value, and the coating layers (12, 13) have a pH value of alkali, and are first regions that are one alkaline region formed on the surface of the central substrate 11. Part 12 and a second region part 13 which is one alkali region formed on the first region part 12. The pH value of the central substrate 11 is neutral, and the pH values of the first region portion 12 and the second region portion 13 are set to different alkali pH values.
[0014]
As is apparent from FIG. 1, the first region portion 12 and the second region portion 13 constitute each layer.
[0015]
The central substrate 11 is made of hydroxyapatite and has a particle size range of 10 to 80 μm. Specifically, it is obtained by collecting and solidifying the particle size of the first and second region portions 12 and 13 with the particle size of the hydroxyapatite particles of 2 μm in the range of 10 to 80 μm.
[0016]
The first region portion 12 is a layer mainly composed of hydroxyapatite. The second region 13 is a layer mainly composed of hydroxyapatite. In this case, the region thickness dimension of the first region portion 12 is in the range of 2 to 10 μm, and the region thickness dimension of the second region portion 13 is in the range of 2 to 10 μm. Here, the region thickness dimension is a dimension in a direction from the surface of the central base material 11 toward the outer surface of the second region part 13. The first region portion 12 and the second region portion 13 are configured to have each region by aggregating hydroxyapatite particles having a particle shape finer than the particle size of the central substrate 11. Specifically, the average particle size of the hydroxyapatite particles in the first and second region portions 12 and 13 is 2 μm.
[0017]
The pH values of the first and second region portions 12 and 13 are set to be in the range of pH 8-10. Specifically, the pH value of the first region portion 12 is set to a range of pH 8 to 9, and the pH value of the second region portion 13 is set to a range of pH 9 to 10. The pH value is stepwise inclined so that the pH value increases from the first region portion 12 on the surface of the central base material 11 toward the second region portion 13 on the outer surface of the central base material 11. I am letting. Specifically, when the pH value of the first region portion 12 is set to pH 9, the pH value of the second region portion 13 is set to pH 10.
[0018]
In this way, by gradually grading the pH value, the acidic body fluid in the inflamed part of the affected part is neutralized in a stepwise manner from an alkali having a high pH value to an alkali having a low pH value to calm the inflamed part.
[0019]
In the embodiment, the pH value is set so that the pH value becomes higher from the first region portion 12 on the surface of the central base material 11 toward the second region portion 13 on the outer surface of the central base material 11. Inclined stepwise, but when a third region (not shown) is formed on the second region 13 or when more than three regions are formed, the pH value is inclined stepwise. It is.
[0020]
The compounding ratio of calcium (Ca) / phosphorus (P) in the hydroxyapatite of the central substrate 11 is 1.67, and the compounding ratio of calcium / phosphorus in the hydroxyapatite of the first region 12 is 1.71 to 1.80. The calcium / phosphorus compound ratio in the hydroxyapatite of the second coating layer 13 is in the range of 1.90 to 2.00.
[0021]
The hydroxyapatite of the central base material 11 with a calcium / phosphorus ratio of 1.67 has a neutral pH value. Moreover, the hydroxyapatite of the 1st area | region part 12 which made the compounding ratio of calcium / phosphorus the range of 1.71-1.80 becomes alkali, and made the compounding ratio of calcium / phosphorus the range of 1.90-2.00. The hydroxyapatite in the second region 13 becomes alkali.
[0022]
Next, a method for manufacturing the granular bone filling material in the first embodiment will be described with reference to FIG. In the manufacturing method of the granular bone filling material, the central base material 11 having a neutral pH value is manufactured (step S1). The central base material 11 is produced by granulating and drying hydroxyapatite synthesized with a calcium / phosphorus compounding ratio of 1.67 using a spray dryer to produce a central base material 11 having a neutral pH value.
[0023]
Next, the 1st area | region part 12 which made pH value alkali is formed in the surface of the center base material 11 (process S2). The hydroxyapatite in the first region 12 is dried after forming a raw slurry of hydroxyapatite synthesized on the surface of the central substrate 11 with a calcium / phosphorus compound ratio of 1.71 to 1.80. It is set as the 1st area | region part 12 which made the value alkali.
[0024]
Furthermore, a second region portion 13 having a pH value of alkali is formed on the first region portion 12 (step S3). The hydroxyapatite in the second region 13 is formed after a raw material slurry of hydroxyapatite synthesized with a calcium / phosphorus compounding ratio in the range of 1.90 to 2.00 is formed on the first region 12, and then dried to a pH value. The second region portion 13 is designated as alkali.
[0025]
FIG. 2 shows the pH value when the granular bone filling material produced by the method for producing the granular bone filling material is immersed in physiological saline. As can be seen from FIG. 2, it can be seen that the pH value approaches neutral with the passage of time from week 1 to week 8.
[0026]
FIG. 3 shows the results of an experiment conducted when a granular bone filling material was embedded in a rat bone. In FIG. 3, the vertical axis represents the bone formation rate (%), and the horizontal axis represents the week (elapse of time). As apparent from FIG. 3, by adopting a granular bone filling material in which the pH value of the second region 13 is 10 than when only hydroxyapatite having a pH value of 7.2 is used, a new bone is obtained. As a result, the formation of was improved.
[0027]
Hereinafter, a second embodiment of the granular bone filling material will be described. In the description of the second embodiment, FIG. 1 will be adopted and the description will be made with reference to the reference numerals in parentheses in FIG.
[0028]
The grain-shaped central base material 21 in the granular bone filling material shown in the second embodiment is hydroxyapatite. The first region 22 is a mixture mainly composed of first chitosan and β-type tricalcium phosphate (β · TPC) having a particle size smaller than that of the central base material 21. The second region portion 23 is a mixture mainly composed of second chitosan and α-type tricalcium phosphate (α · TPC) having a particle size smaller than that of the central base material 21.
[0029]
Since α-type tricalcium phosphate has the property of easily eluting calcium ions and phosphorus ions, it easily elutes calcium ions and phosphorus ions into body fluids. Can be neutralized.
[0030]
Further, as in the first embodiment, the average particle size of the particles in the β-type tricalcium phosphate in the first region portion 22 and the α-type tricalcium phosphate in the second region portion 23 is set to 2 μm. The pH value of the 1st and 2nd area | region parts 22 and 23 is set to the range of pH8-10. In this case, the pH value of the second region portion 23 is set to be higher than the pH value of the first region portion 22. That is, the pH value of the first region portion 22 is in the range of pH 8-9, and the pH value of the second region portion 13 is in the range of pH 9-10.
[0031]
Further, the calcium / phosphorus compounding ratio in the hydroxyapatite of the central base material 21 is 1.67, and the calcium / phosphorus compounding ratio in the β-type tricalcium phosphate in the first region 12 is 1.71 to 1.80. As a range, it is good also considering the compounding ratio of calcium / phosphorus in the alpha type tricalcium phosphate of the 2nd field part 23 as the range of 1.90-2.00.
[0032]
Hereafter, the manufacturing method of the granular bone filling material in 2nd Embodiment is demonstrated, referring FIG.1 and FIG.4. In this method for producing a granular bone filling material, the central base material 21 having a neutral pH value is produced (step S11). This process S11 is the same process as process S11 of the manufacturing method of the granular bone filling material in the first embodiment.
[0033]
Next, the 1st area | region part 22 which made the pH value alkali is formed on the surface of the center base material 11 (process S12). In the step S12 of forming the first region 22 having an alkaline pH value on the surface of the central base material 21, the first chitosan is dissolved with the first organic acid and the first physiological saline to obtain the first A step of forming a chitosan sol, a step of kneading β-type tricalcium phosphate in the first chitosan sol to form a first paste, and spraying the first paste onto the surface of the central substrate 21 to A step of forming the first region portion 22 on the surface is included. Specifically, 10 g of the first chitosan, 10 g of the first organic acid, and 50 ml of the first physiological saline are dissolved to form a first chitosan sol.
[0034]
In process S12 of the 1st field part 22, the 1st field part 22 is gelled with the 1st gelatinizer alkali aqueous solution of the 1st chitosan sol. As the first gelling agent alkaline aqueous solution, for example, a first calcium hydroxide (3% CaOH) solution is used and gelled with the first calcium hydroxide to fix β-type calcium triphosphate as an alkali.
[0035]
In the step of spraying the first paste onto the surface of the central base material 21 to form the first region 22 on the surface of the central base material 21, as shown in FIG. The first base portion 21 is formed on the surface of the central base material 21 by the first paste 31 sprayed from the nozzle 43 while the central base material 21 is placed on the central base material 21 and rolled.
[0036]
Further, the second region portion 23 having an alkaline pH value is formed on the first region portion 22 (step S13). In the step S13 of forming the second region portion 23 on the first region portion 22, the step of dissolving the second chitosan with the second organic acid and the second physiological saline to form a second chitosan sol; A step of kneading α-type tricalcium phosphate into the chitosan sol of No. 2 to form a second paste, and spraying the second paste onto the surface of the first region portion 22 to form a second region on the first region portion 22 Forming the portion 23. Specifically, 10 g of the second chitosan, 10 g of the second organic acid, and 50 ml of the second physiological saline are dissolved to form a first chitosan sol.
[0037]
In step S13 of the second region portion 23, the second region portion 23 is gelled with the second gelling agent alkaline aqueous solution of the second chitosan sol. As the second gelling agent alkaline aqueous solution, for example, a second calcium hydroxide (3% CaOH) solution is used and gelled with the second calcium hydroxide to fix α-type calcium triphosphate as an alkali.
[0038]
In the step of spraying the second paste onto the surface of the first region portion 22 to form the second region portion 23, as shown in FIG. 4, the central substrate 21 is placed on the rotary table 42 that is rotated by the drive source 41. The second paste 32 sprayed from the nozzle 43 while rolling the first region portion 22 including the central base material 21 with the first region portion 22 including the reference numeral described in parentheses in FIG. The second region portion 23 is formed on the surface of the first region portion 22 by referring to FIG.
[0039]
In addition, in the manufacturing method of the granular bone filling material, the calcium / phosphorus compounding ratio in the hydroxyapatite of the central base material 11 is 1.67, and the calcium / phosphorus of β-type tricalcium phosphate in the first region 12 is The blending ratio is in the range of 1.71 to 1.80, and the blending ratio of calcium / phosphorus in the α-type tricalcium phosphate in the second region portion 23 is in the range of 1.90 to 2.00.
[0040]
FIG. 5 shows the pH value when the granular bone filling material produced by the method for producing the granular bone filling material is immersed in physiological saline. As can be seen from FIG. 5, it can be seen that the pH value approaches neutral with the passage of time from week 1 to week 7.
[0041]
FIG. 6 shows the results of an experiment conducted when a granular bone filling material was embedded in a rat bone. In FIG. 3, the vertical axis represents the bone formation rate (%), and the horizontal axis represents the week (time). As is clear from FIG. 3, by using the granular bone filling material of the present invention (abbreviated as MH in FIG. 3) rather than using only hydroxyapatite having a pH value of 7.2. As a result, the formation of new bone was improved.
[0042]
The method for forming the first and second region portions 22 and 23 using the drive source 41 and the rotary table 42 described in the second embodiment is the same as the granular bone filling material in the first embodiment. It can also be applied in the course of the manufacturing method.
[0043]
In the first and second embodiments, the first region portion 12 (or 21) and the second region portion 13 (or 23) have been described. However, on the surface of the central substrate 11 (or 21). Further, two or more regions may be formed. Also in this case, the pH value of the alkali is inclined in steps.
[0044]
Further, a little neutral particles may be included in the alkali region. Furthermore, a region of one layer is formed on the surface of the central substrate 11 (or 21), and the pH value is increased from the surface side of the central substrate 11 (or 21) to the outside in the region. May be configured so as to incline the pH value of the alkali step-by-step by constituting an alkali distribution including multiple alkali regions having different values.
[0045]
【The invention's effect】
As described above with reference to each embodiment, according to the granular bone filling material according to the present invention, the pH value of the central base material is neutral, the pH value of the region portion is alkaline, It is composed of multiple alkali regions with different pH values, and the pH value of the alkali is gradually inclined from the inside to the outside, so that the acidic body fluid can be neutralized and replaced with new bone in vivo Since the time until it is done can be shortened, bone formation can be promoted.
[0046]
Further, according to the method for producing a granular bone filling material according to the present invention, a central base material having a neutral pH value is manufactured, and the region portion is formed so as to gradually incline the pH value of the alkali from the inside to the outside. Since it is formed on the surface of the central base material so that multiple alkali regions having different pH values of alkalis can be obtained, a granular bone filling material that promotes bone formation can be obtained by a simple and safe manufacturing method. .
[Brief description of the drawings]
FIG. 1 is a cross-sectional view showing a schematic configuration of a granular bone filling material, showing first and second embodiments of the granular bone filling material according to the present invention.
FIG. 2 is a graph showing pH values when the granular bone filling material in the first embodiment shown in FIG. 1 is immersed in physiological saline.
FIG. 3 is a graph showing the results of experiments conducted by implanting the granular bone filling material in the first embodiment shown in FIG. 1 into the bones of rats.
FIG. 4 shows an example of a method for producing a granular bone filling material in the second embodiment shown in FIG. 1, and shows a state when a first base layer is coated on a central base material using a rotary table. It is a side view.
FIG. 5 is a graph showing a pH value when the granular bone filling material in the second embodiment shown in FIG. 1 is immersed in physiological saline.
FIG. 6 is a graph showing the results of experiments conducted by implanting the granular bone filling material in the second embodiment shown in FIG. 1 into the bones of rats.
[Explanation of symbols]
11, 21 Central base material 12, 22 1st area | region part 13 and 23 2nd area | region part

Claims (18)

In a granular bone filling material comprising a granular base material and a coating layer covering the surface of the central material, wherein the central material and the coating layer are calcium phosphate compounds, A granular bone filling material, characterized in that the pH value is neutral, and the coating layer is composed of multiple alkaline regions in which the pH value is alkaline and the pH values of the alkali are different from each other. The granular bone grafting material according to claim 1, wherein the covering layer has a plurality of the alkali regions so that the pH value of the alkali increases from the surface of the central substrate toward the outer surface of the covering layer. A granular bone filling material characterized by being made. The granular bone filling material according to claim 2, wherein the alkali region has a first region portion formed on a surface of the central base material and a second region portion formed on the first region portion. The granular bone filling material, wherein the pH value in the first region is in the range of pH 8-9. The granular bone filling material according to claim 3, wherein the central base material is hydroxyapatite, the main component of the first region is hydroxyapatite, and the main component of the second region is hydroxyapatite. A granular bone filling material characterized by The granular bone filling material according to claim 4, wherein a calcium / phosphorus compound ratio in the hydroxyapatite of the central substrate is 1.67, and a calcium / phosphorus compound ratio in the hydroxyapatite in the first region portion. Is in the range of 1.71 to 1.80, and the calcium / phosphorus compound ratio in the hydroxyapatite of the second region is in the range of 1.90 to 2.00. . The granular bone filling material according to claim 3, wherein the central base material is hydroxyapatite, and the first region portion includes first chitosan and β-type tricalcium phosphate as main components, The region portion contains a second chitosan and α-type tricalcium phosphate as main components, and a granular bone filling material. The granular bone filling material according to claim 6, wherein the calcium / phosphorus compounding ratio in the hydroxyapatite of the central substrate is 1.67, and the calcium / phosphorus in the β-type tricalcium phosphate in the first region portion. The blending ratio of 1.71 to 1.80 is in the range, and the blending ratio of calcium / phosphorus in the α-type tricalcium phosphate in the second region is in the range of 1.90 to 2.00. Granular bone filling material. The granular bone filling material according to any one of claims 1 to 7, wherein the central base material has a particle shape dimension in a range of 10 to 80 µm, and a plurality of region thickness dimensions of the alkali region configured in a multiple manner. Each of which is in the range of 2 to 10 μm. In the method for producing a granular bone filling material, comprising a grain-shaped central base material and a coating layer covering the surface of the central base material, wherein the central base material and the coating layer are calcium phosphate compounds. A step of producing the neutral base material, and a step of forming the coating layer on the surface of the central base material as a plurality of alkali regions having different alkali pH values. Of manufacturing a bone substitute material. 10. The method for producing a granular bone filling material according to claim 9, wherein the alkali region is formed in multiple layers so that the pH value of the alkali increases from the surface of the central substrate toward the outer surface of the coating layer. A method for producing a granular bone filling material. The method for producing a granular bone filling material according to claim 10, wherein a first region portion of the alkali region is formed on a surface of the central base material, and a second region portion of the alkali region is formed on the first region portion. And the pH value in the first region is in the range of pH 8-9. The method for producing a granular bone filling material according to claim 11, wherein the central base material is hydroxyapatite, the main component of the first region is hydroxyapatite, and the main component of the second region is hydroxyapatite. A method for producing a granular bone filling material. 13. The method for producing a granular bone grafting material according to claim 12, wherein a calcium / phosphorus compounding ratio in the hydroxyapatite of the central base material is 1.67, and calcium / phosphorus in the hydroxyapatite in the first region portion. Granular bone, characterized in that the blending ratio is in the range of 1.71 to 1.80, and the blending ratio of calcium / phosphorus in the hydroxyapatite in the second region is in the range of 1.90 to 2.00. A method of manufacturing a filling material. The method for producing a granular bone filling material according to claim 11, wherein the central base material is hydroxyapatite, and the first chitosan and β-type tricalcium phosphate are mixed as main components to form the first region portion. A method for producing a granular bone filling material, characterized in that the second region portion is formed by mixing second chitosan and α-type tricalcium phosphate as main components. The method for producing a granular bone filling material according to claim 14, wherein a calcium / phosphorus compound ratio in the hydroxyapatite of the central base material is 1.67, and the β-type tricalcium phosphate in the first region portion is used. The blending ratio of calcium / phosphorus is in the range of 1.71 to 1.80, and the blending ratio of calcium / phosphorus in the α-type tricalcium phosphate in the second region is in the range of 1.90 to 2.00. A method for producing a granular bone filling material. 12. The method for producing a granular bone grafting material according to claim 11, wherein the first chitosan is added to the first organic acid and the first in the previous step of forming the first region portion on the surface of the central substrate. A first chitosan sol by dissolving with physiological saline and a step of kneading the β-type tricalcium phosphate into the first chitosan sol to form a first paste, the first region portion Forming the first region on the surface of the central substrate by spraying the first paste onto the surface of the central substrate to form the first region. 1. A method for producing a granular bone filling material, comprising the step of gelling with an alkaline aqueous solution of 1 chitosan sol and fixing the β-type calcium triphosphate on the first region. The method for producing a granular bone filling material according to claim 16, wherein in the previous step of forming the second region portion on the first region portion, the second chitosan is added to the second organic acid and the second region. A step of dissolving in physiological saline to form a second chitosan sol, and a step of kneading the α-type tricalcium phosphate into the second chitosan sol to obtain a second paste, In the step of forming the second region portion, the step of spraying the second paste onto the surface of the central substrate to form the second region portion, and the step of forming the second region portion into the second region. A method for producing a granular bone filling material, comprising the step of gelling with a second gelling agent alkaline aqueous solution of chitosan sol and fixing the α-type calcium triphosphate on the second region. The method for producing a granular bone filling material according to any one of claims 9 to 17, wherein a particle size of the central base material is in a range of 10 to 80 µm, and the alkali region is configured in multiple layers. A method for producing a granular bone filling material, characterized in that each thickness dimension is in the range of 2 to 10 μm.

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