JP5936083B2 - Method for producing hydroxyapatite crystals - Google Patents

Description

  The present invention relates to a method for producing hydroxyapatite crystals, and more particularly to a method for producing apatite crystals by starting synthesis in an acidic solution state.

  Hydroxyapatite is applied in a very wide range, and is used for, for example, artificial tooth roots, artificial bone raw materials, adsorbents, various catalysts, temperature sensors and the like.

  Hydroxyapatite production methods include an aqueous solution reaction, a solid phase reaction, and a melt starting method.

  In the case of the aqueous solution reaction, the crystallinity of the apatite to be produced is low, and it is difficult to produce apatite with a single crystal and a large particle diameter even if the hydrothermal aqueous solution reaction is used.

  In the case of a solid phase reaction, the crystallinity is developed, so that it cannot be used as a raw material for sintering.

  When the pulling method or the flux method is applied starting from the melt, it cannot be applied to the synthesis of hydroxyapatite because it cannot supply hydroxide ions.

  Hydrothermal growth is often used to produce large single crystals of hydroxyapatite. For example, Arends et al. In Non-Patent Document 1 (Journal of Crystal Growth Vol. 46, P213-220 (1979)) has a growth temperature of 430 to 500 ° C., a pressure of 200 MPa, a growth period of 20 to 70 days, and a major axis of 0.1 mm. Columnar hydroxyapatite single crystals of up to 3 mm are grown.

  However, according to this, there is a problem that the growing period is extremely long, it is not suitable for industrialization, and complicated chemical substances are required. In particular, since the pressure (200 MPa) and the growth temperature (430 ° C. or higher) of the synthesis environment are high, the problem is that the synthesis apparatus becomes large and expensive.

For example, there are research examples such as Roy (103 MPa, 745 to 900 ° C.), Mengeot (310 MPa or more, 390 ° C. or more), and Sweetsugu (54 MPa, 1400 ° C.).
Japanese Patent Laid-Open No. 11-343198 JP-A-7-2505 Arends et al., Journal of Crystal Growth 46, P213-220 (1979)

  In view of the above points, an object of the present invention is to provide a method capable of producing a hydroxyapatite crystal at a lower pressure and a lower temperature.

  Here, the condition of acidity is generally unsuitable for apatite production. Therefore, as disclosed in Patent Document 2 (Japanese Patent Application Laid-Open No. 7-2505), it is common to generate crystals while keeping the solution alkaline.

  The present inventor has eagerly studied to search for a new technique different from the general technique, succeeded in producing a hydroxyapatite crystal at low pressure and low temperature, and completed the present invention.

  In the method for producing hydroxyapatite crystals according to the present invention, water is added to polymerized phosphoric acid and calcium salt, or synthesis is started as an acidic solution by adding polymerized phosphoric acid aqueous solution to calcium salt to hydrolyze polymerized phosphoric acid. Apatite crystals are produced by the release of phosphate ions and the release of calcium ions accompanying a decrease in chelating ability.

  According to the present invention, as will be apparent from the following description, apatite crystals can be generated at a much lower pressure and lower temperature than in the prior art, so the scale of the synthesis apparatus can be reduced and the construction can be made inexpensively.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings.

  The method for producing a hydroxyapatite crystal according to the present invention comprises synthesizing an acidic solution by adding water to a mixture of polymerized phosphoric acid and calcium ions, releasing phosphate ions accompanying the hydrolysis of polymerized phosphoric acid, chelating Apatite crystals are produced by the release of calcium ions accompanying a decrease in ability.

  Preferably, the growth temperature is 200 ° C. and the pressure is 1.5 MPa. Of course, these numerical values are merely examples, and the present invention is not limited to these numerical values.

  Preferably, the polymerized phosphoric acid includes at least one of polyphosphoric acid and condensed phosphoric acid, and calcium ions are supplied by calcium oxide.

  The polymerized phosphoric acid may be obtained by either a chemical method or a biological method, and typically includes at least one of polyphosphoric acid or condensed phosphoric acid.

  Calcium ions are preferably supplied by calcium oxide, calcium hydroxide or the like.

  The basis of this method is that apatite is produced by adding water to a mixture of polymerized phosphoric acid and calcium ions to react, but is characterized in that synthesis starts when the solution is in an acidic state.

  Polyphosphate is a chain of phosphoric acid, and is hydrolyzed from the end of the chain by heating and phosphatase, supplying phosphate ions, and binding to calcium to promote apatite formation.

  If conditions (alkalineity) appropriate for apatite formation are given from the beginning, calcium and phosphoric acid begin to bond immediately and precipitate as fine crystals. For this reason, crystals cannot grow greatly.

  In this method, synthesis is started from an acidic condition unsuitable for apatite formation, so that calcium and phosphoric acid do not immediately start bonding immediately after the start. However, after that, the reaction proceeds due to hydrolysis of polyphosphoric acid, and PH increases.

  In this method, columnar apatite crystals having a major axis of 0.1 mm to a maximum of 5 mm can be obtained at a growth temperature of 200 ° C., 1.5 MPa, and a growth period of 1 to 7 days.

  Chemical substances such as ammonium hydrogen phosphate and calcium chloride are often used to supply phosphoric acid as a starting material for synthesis.

  If ions that do not constitute hydroxyapatite, such as nitric acid, hydrochloric acid, carbonic acid, ammonium, potassium, etc., are mixed in the synthetic system, it is difficult to enter and exclude the hydroxyapatite skeleton having high ion adsorption ability.

  The synthesis system of this method does not require anything other than phosphoric acid, calcium, and water, and since the base point of synthesis is started from an acidic solution, the alkaline solution also has the effect of eliminating carbon dioxide in the atmosphere that is strongly absorbed. is there.

  The chelate adsorption ability of polyvalent metal ions of polyphosphoric acid is widely known, and an ion to be incorporated may be chelated with polyphosphoric acid in advance, and this polyphosphoric acid may be used as a synthetic base point.

  For example, apatite in which a radioactive substance is confined in a skeleton is generated by adsorbing and removing a radioactive substance from water contaminated with a radioactive substance (radioactive strontium, radioactive cesium, etc.) and apatite synthesis. Since the produced apatite is solid, it is easy to handle, and PH is stable from a neutral range to an alkaline range.

  Since the method for producing a hydroxyapatite crystal of the present invention is simple and under low-temperature and low-pressure conditions, apatite having a wide range of applications in various fields can be produced.

Each example will be described below with reference to photographs and graphs.
Example 1
In this example, as described above, the growth temperature is 200 ° C., 1.5 MPa, and the growth period is 1 to 7 days.

  FIG. 1 is a 100 × micrograph showing an apatite crystal according to Example 1 of the present invention, and FIG. 2 is a macro photograph of the apatite crystal of the present invention.

  1 and 2, it can be seen that columnar apatite crystals having a major axis of 0.1 mm to a maximum of 5 mm are obtained.

(Example 2)
In this example, 2 g of polyphosphoric acid and 10 ml of water were added to 2.5 g of calcium oxide, stirred, moored in an electric furnace at 200 ° C. for 1 week, washed and dried.

  FIG. 3 is an SEM image after drying according to Example 2 of the present invention. The Ca / P molar ratio of the entire visual field in FIG. 3 is 2.3, but the Ca / P molar ratio is 1.36 in the point analysis of the crystal in the center of FIG.

  When the result of FIG. 3 was analyzed, it was found that calcium hydroxide and hydroxyapatite were mixed. The crystal has a clear hexagonal columnar shape, and since calcium, phosphate ions, water, and finally alkaline water were used in the synthetic system, columnar hydroxyapatite crystals were obtained.

  The crystal alone was picked up and measured by microscopic Raman, and was found to be a hydroxyapatite crystal. In addition, it is thought that the fine powder shown by FIG. 3 is mixed as calcium hydroxide.

(Example 3)
In this example, 2 grams of polyphosphoric acid and a predetermined amount of calcium oxide were mixed, 10 CC of water was added, and hydrothermal synthesis was performed at 200 ° C. for 24 hours.

  FIG. 4 is a photograph in the case of mixing 3 grams of calcium oxide in Example 3 of the present invention, and FIG. 5 is a graph showing an X-ray diffraction pattern in the same case.

  FIG. 6 is a photograph in which 2.5 grams of calcium oxide is mixed in Example 3 of the present invention, and FIG. 7 is a graph showing an X-ray diffraction pattern in the same case.

  FIG. 8 is a photograph in which 1.5 grams of calcium oxide is mixed in Example 3 of the present invention, and FIG. 9 is a graph showing an X-ray diffraction pattern in the same case.

  As can be seen from FIGS. 4 and 6, there are many rod-like crystals when the calcium oxide is 3 grams or 2.5 grams.

  As can be seen from FIG. 8, many plate-like crystals exist when the calcium oxide is 1.5 grams.

  According to the X-ray diffraction analysis shown in FIGS. 5, 7, and 9, the rod-like crystals are hydroxyapatite, and the plate-like crystals are considered to be monetite.

Example 4
In this example, hydrothermal synthesis was performed at 200 ° C. for 5 days with 2.5 grams of calcium oxide and 2 grams of polyphosphoric acid. FIG. 10 is a graph showing an X-ray diffraction pattern and the like in Example 4 of the present invention.

  On the first day of the five days, calcium phosphate components other than apatite were observed, but these components disappeared and calcium hydroxide remained.

  FIG. 11 is a SEM photograph taken on the fifth day in the case where the calcium oxide was 2.4 grams in Example 4 of the present invention. It will be understood that many columnar crystals are distributed.

(Example 5)
In this example, 10 grams of water was added to 2 grams of polyphosphoric acid to 2 grams of calcium oxide, and one day had elapsed at a growth temperature of 200 ° C.

  12 is a photograph showing the entire field of view in Example 5 of the present invention, FIG. 13 is a photograph focusing on the rod-shaped crystal portion of FIG. 12, and FIG. 14 is focusing on the lower plate-shaped crystal portion of FIG. FIG. 15 is a photograph focusing on the upper plate-like crystal portion of FIG.

  Elemental analysis of the entire field of view shown in FIG. 12 revealed that the molar ratio of Ca / P in the entire field of view was 1.43, and the cubic crystals did not contain phosphorus.

  In the rod-like crystal portion shown in FIG. 13, the Ca / P molar ratio is 1.75, and in the lower plate-like crystal portion shown in FIG. 14, the Ca / P molar ratio is 1.47. In the upper plate crystal portion shown in FIG. 15, the Ca / P molar ratio is 0.957.

(Example 5)
The following technique is also effective if a huge crystal is not required. That is, hydrolysis of polymerized phosphoric acid occurs even at a low temperature of 70 ° C. or lower, and apatite itself can be generated. However, low-grade calcium phosphate is included, and the size of the crystals is smaller than in Examples 1-4.

  However, even if it has a small diameter, it can be contained in toothpaste, or can be put into practical use as a substitute for commercially available fine particles, and the manufacturing cost can be made lower than that of the conventional method.

  Furthermore, in the presence of a polymerized phosphate degrading enzyme such as phosphatase in the living body (where bone is formed in the living body), the hydrolysis of the polymerized phosphate can be performed even at a lower temperature (for example, body temperature). Decomposition occurs and similar apatite can be produced.

  Such apatite has a low degree of crystallization, but has a high reaction activity and is unstable, and therefore has a property of being easily broken and absorbed in the body. For this reason, there exists an advantage that it can be used conveniently for the use as a bone filling material, for example.

  As described above, according to Example 5, there is an advantage that useful apatite having a small diameter can be generated much more easily and inexpensively than the conventional method. In Example 5, points not particularly mentioned are the same as in Example 1.

  In any of Examples 1 to 5, apatite crystals may be generated by decomposing polyphosphoric acid in the presence of ultraviolet light. Although the generation speed is low, three-dimensional modeling is possible. More specifically, using a three-dimensional printer, crystallization can be generated photochemically to form a three-dimensional structure of bones and teeth. In addition, when fluorine is added in the synthesis system, the reaction can be accelerated.

100-fold photomicrograph showing an apatite crystal according to Example 1 of the present invention. Macro shot of the apatite crystal of the present invention SEM image after drying according to Example 2 of the present invention Photograph when 3 grams of calcium oxide is mixed in Example 3 of the present invention Graph showing X-ray diffraction pattern in the same case Photograph when 2.5 grams of calcium oxide were mixed in Example 3 of the present invention Graph showing X-ray diffraction pattern in the same case Photograph when 1.5 g of calcium oxide is mixed in Example 3 of the present invention Graph showing X-ray diffraction pattern in the same case The graph which shows the X-ray-diffraction figure in Example 4 of this invention In Example 4 of the present invention, the SEM photograph was taken on the fifth day when the calcium oxide was 2.4 grams. Photograph showing the entire visual field in Example 5 of the present invention Photograph focusing on the portion of the rod-shaped crystal in FIG. A photograph focusing on the lower plate-like crystal part of FIG. A photograph focusing on the upper part of the plate crystal in FIG.

Claims (3)

Add water to polymerized phosphoric acid and calcium salt, or add polymerized phosphoric acid aqueous solution to calcium salt, start synthesis as acidic solution, release phosphate ion accompanying hydrolysis of polymerized phosphoric acid, decrease chelating ability A method for producing a hydroxyapatite crystal, characterized in that an apatite crystal is produced by the release of accompanying calcium ions. Nurturing temperature is the 200 ° C., and method of manufacturing the hydroxyapatite crystals of claim 1, wherein the pressure is 1.5 MPa. The method for producing a hydroxyapatite crystal according to claim 1 or 2, wherein the polymerized phosphoric acid includes at least one of polyphosphoric acid and condensed phosphoric acid, and the calcium ions are supplied by calcium oxide.