JPH0324404B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to a method for producing hydroxyapatite (HAP). In recent years, phosphoric acid compounds, especially
HAP has attracted attention and is being used in artificial bones, artificial teeth, etc. This means that when HAP is implanted in a living body,
This is because it is safe and chemically stable, and it is easy to fuse with natural bone without causing a rejection reaction in vivo. Other uses of HAP include raw material for bone china, a type of high-grade porcelain,
Alternatively, there are packing materials for chromatography, etc. [Prior art] In general, two methods are known for producing HAP: a dry method using a solid phase reaction at high temperatures, and a wet method using a hydro-liquid reaction or hydrothermal reaction at atmospheric pressure. The reaction requires long firing at a high temperature of 1000°C or higher, and the equipment is expensive, so it cannot be called an industrial method. In addition, among the wet methods, _CaHPO4・
A method based on the reaction of 2H ₂ O (or CaHPO ₄ ) and Ca(OH) ₂ is known (Japanese Patent Application Laid-open No. 111000/1983).
In this method, each raw material is mixed solidly, and this mixture is heated at 100 to 500℃ for 1 hour using an autoclave.
This method produces crystalline HAP by carrying out a hydrothermal reaction under hydrothermal conditions of ~500 atm. but,
This method has the disadvantage that the reaction conditions are harsh, the reaction equipment is expensive, and the energy cost is also high. On the other hand, as a method for producing HAP using an aqueous solution method,
A method using neutralization of phosphoric acid is known, but the reaction rate is high and the resulting precipitate is colloidal, which is inconvenient in terms of handling and operation. In addition, when using HAP as a biological material, which is the main use of HAP, if it contains more than a certain amount of iron, zinc, lead, etc., these ions may be eluted in the living body, so HAP must be made with very few impurities. Therefore, when using phosphoric acid as a raw material, it becomes extremely difficult to remove impurities. As an extremely industrial method that is completely different from the above method, the present inventors have already added Ca(OH) ₂ to a slurry of CaHPO ₄ 2H ₂ O and water, and created an aqueous solution in which the reaction takes place under atmospheric pressure. (Japanese Patent Publication No. 2011). This method easily and quickly produces high purity by adding Ca(OH) ₂ gradually to keep the pH below 10 until the Ca/p molar ratio is 1.6.
It is possible to produce HAP. [Problems with the Prior Art] Among the HAP production methods proposed so far, both the dry method and the hydrothermal reaction method require expensive equipment and are disadvantageous in terms of energy.
Furthermore, among the aqueous solution methods, the method using phosphoric acid neutralization has problems in handling the product and is not suitable for producing high-purity HAP. On the other hand, in the method already proposed by the present inventors, the Ca/p molar ratio of HAP once generated may vary during the filtration and washing operation, and the desired Ca/p molar ratio can be achieved with good reproducibility. Obtaining HAP was not always satisfying. [Problems to be Solved by the Invention] The present invention is intended to solve the above-mentioned problems of the prior art. Ratio HAP
The purpose is to obtain. [Means for solving the problem] That is, the present invention adds CaO and/or Ca(OH) ₂ to a slurry of CaHPO ₄ 2H ₂ O and water,
In a method for producing hydroxyapatite,
Add CaO and/or Ca(OH) ₂ while keeping the pH below 10 at a temperature of 5 to 70°C up to a Ca/p molar ratio of 1.54, then add the remaining amount and separate the resulting solid. This is a method for producing hydroxyapatite, which is characterized by heating to 100°C or higher. To explain the present invention in more detail, _CaHPO4・
The basic reaction formula when using 2H ₂ O and Ca(OH) ₂ as a Ca source is shown below. 6CaHPO ₄・2H ₂ O＋4Ca(OH) ₂ →Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ↓＋18H ₂ O In this case, an equivalent amount of Ca is added to a slurry solution of CaHPO ₄・2H ₂ O and water at a reaction temperature of 100℃ or less. Even if (OH) ₂ is added all at once, the reaction is extremely slow and it is difficult to generate HAP.
However, when Ca(OH) ₂ is supplied continuously or intermittently to the CaHPO ₄ 2H ₂ O slurry within a range that does not exceed each reaction rate, it is necessary to ensure that the PH value of the reaction solution does not exceed a specific value. while adjusting to
If Ca(OH) ₂ solution is supplied, the reaction will proceed easily and be completed. Controlling the pH is a major factor in this reaction; for example, at a reaction temperature of 50°C, the reaction is carried out at a pH of 10 or lower, preferably 9.0 or lower, up to a Ca/p molar ratio of 1.58. Thereafter, the reaction is carried out at a pH of 9 or higher to synthesize HAP with a theoretical Ca/p ratio of 1.67. Also,
Even if the charged Ca/p ratio slightly exceeds 1.67, Ca(OH) ₂ can be removed by washing in the subsequent stage.
HAP with a Ca/p ratio of 1.67 can be easily obtained. In this reaction, the pH during the reaction is an extremely important factor, and in order to complete the reaction, sufficient attention must be paid to pH control.In particular, the amount of Ca(OH) ₂ added must be up to 80% of the theoretical amount added. If the pH is not kept below 10, unreacted CaHPO ₄ 2H ₂ O remains and HAP cannot be obtained. The reaction temperature is usually 5 to 70°C, but preferably 30 to 70°C in order to speed up the reaction. 5
At temperatures below ℃, the reaction progresses slowly and is unfavorable, and at temperatures above 70℃, CaHPO ₄ 2H ₂ O
It metastasizes to _CaHPO4 and should be avoided. In addition, the Ca/p ratio of the product HAP can be adjusted by changing the amount of Ca(OH) ₂ supplied (the charged Ca/p ratio).
HAP with a Ca/p ratio of 1.48 to 1.67 can be easily obtained. After the HAP produced in this way is separated by filtration using conventional means, the separated product is heated at 100°C or higher.
More preferably, it is heated to 130°C or higher. The heating time may be selected depending on the heating temperature and the water content of the separated material so that the water content at the end of heating is 5% or less. This treatment allows for cleaning in the next step.
This can prevent the Ca/p molar ratio from changing. Furthermore, in the present invention, the Ca(OH) ₂ used may be supplied in the form of powder or slurry. Moreover, it is of course possible to use CaO instead of Ca(OH) ₂ . Furthermore, in order to suppress the contamination of CO ^2-3 ions into the product HAP as low as possible, it is desirable to carry out _the reaction under an inert gas (for example, N ₂ etc.) atmosphere. HAP obtained in the present invention is a fine particle plate-like powder, and can be used as a biomaterial as it is or by molding or sintering with other organic materials such as cellulose or collagen, or as a composite with other organic or inorganic matrices. It can also be fully used as a chromatography packing material. The present invention will be explained in detail below with reference to Examples. Examples 1 to 8, Comparative Examples 1 and 2 60 with lid made of SUS304 with hot water jacket
A stirrer, a PH meter, a thermometer, and a reflux condenser are set in the reactor, and CaHPO ₄ 2H ₂ O is charged into the reactor along with water, heated, and when the predetermined temperature is reached, a separate stirrer is installed. 10% lime milk preheated by a hot water jacket was supplied from the lime milk tank to the reactor using a pump, and the reaction was carried out. After the reaction was completed, the product was filtered, heated, washed with water to remove excess Ca(OH) ₂ , and dried. The reaction conditions and results are shown in Table 1. Furthermore, the relationship between the PH and the addition rate of Ca(OH) ₂ at each reaction time in Example 1 is shown in FIG. 1, and the X-ray diffraction pattern of the obtained product is shown in FIG.

〔Effect of the invention〕

According to the present invention, hydroxyapatite, which is useful as a biomaterial, can be easily obtained, and the desired Ca/p ratio can be obtained with good reproducibility.

[Brief explanation of the drawing]

Figure 1 shows the results at each reaction time in Example 1.
2 is a graph showing the relationship between PH and Ca(OH) ₂ addition rate.
FIG. 2 and FIG. 3 are X-ray diffraction patterns of Example 1 and Comparative Example 3, respectively.

Claims (1)

[Claims] 1. A method for producing hydroxyapatite by adding CaO and/or Ca(OH) ₂ to a slurry of CaHPO ₄ 2H ₂ O and water at a temperature of 5 to 70°C.
up to a Ca/P molar ratio of 1.54, add CaO and/or Ca(OH) ₂ while keeping the pH below 10, then add the remaining amount, separate the resulting solid, and heat the separated solid to 100°C or higher. A method for producing hydroxyapatite, which comprises heating.