JP2776049B2 - Method for producing tertiary calcium phosphate and hydraulic calcium phosphate cement - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a third hydration-active tertiary hydrate.
The present invention relates to a method for producing calcium phosphate and a hydraulic calcium phosphate cement that can be used as a filler for a bone defect and a bone cavity or a dental root canal.

[0002]

2. Description of the Related Art Hydraulic calcium phosphate is useful as a restoration material for teeth and bones because it is converted into a compound similar to the main components of teeth and bones in vivo by setting and hardening.
Furthermore, it is known that it is useful as an adsorbent for biopolymers and harmful organic substances or inorganic ions in living bodies.

Conventionally, as the hydraulic calcium phosphate, a calcium phosphate cement using a combination of a salt and a dilute acid as a hardening solution in JP-A-59-88351, and a non-volatile calcium phosphate in JP-A-60-253454. Calcium phosphate cements using acidic solutions containing saturated carboxylic acid polymers are disclosed.
However, in the hydraulic calcium phosphate, there is a problem that until the hardening of the cement is completed, the acidity of the hardening solution is strong, which considerably irritates the living body,
Furthermore, even after the hardening of the cement is completed, the pH is lowered due to the elution of unreacted acid, resulting in a problem that the living body is stimulated.

In order to solve such a problem, a hydraulic calcium phosphate cement which hardens with water has been developed (for example, FC REPORT, vol. 6 (19).
88), p. 475-480 "Hydraulic apatite as bioceramics"). Examples of the hydraulic calcium phosphate hardened by water include JP-A-64-37445.
In the official gazette, simply mixing with water at 37 ° C.
There has been proposed a hydraulic calcium phosphate cement that hardens in about 10 minutes. The hydraulic calcium phosphate has a pH
Is almost neutral, has little irritation to the living body, and solves the problems of the conventional hydraulic calcium phosphate cement.

[0005] However, the hydraulic calcium phosphate does not exhibit sufficient strength for practical use, and its strength deteriorates when left in water for a long period of time. There's a problem.

[0006]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide water that is free from irritation to living organisms, has excellent biocompatibility, has sufficient strength for practical use, and does not deteriorate in strength for a long period of time. It is to provide a hard calcium phosphate cement.

Another object of the present invention is to provide a method for producing tertiary calcium phosphate which can be used as one of the main components of the hydraulic calcium phosphate cement and has a high hydration activity.

[0008]

According to the present invention, a water temperature 1 is provided.
A calcium feedstock in an aqueous solution at 5 ° C. or lower ;
A method for producing tricalcium phosphate, characterized in that a raw material slurry obtained by wet synthesizing a raw material component containing orthophosphoric acid as a phosphorus supply raw material is dried and then calcined at 700 ° C. or higher.

According to the present invention, a calcium supply material and a phosphorus supply material are prepared in an aqueous solution having a water temperature of 15 ° C. or less.
A raw material slurry obtained by wet-synthesizing a raw material component containing orthophosphoric acid as a third component is dried, and then calcined at 700 ° C. or higher to obtain a third calcium phosphate, a second calcium phosphate, and / or a second calcium phosphate.
Alternatively, there is provided a hydraulic calcium phosphate cement containing a powder and a liquid containing a mixture with the first calcium phosphate as a main component.

Hereinafter, the present invention will be described in more detail.

The method for producing the third calcium phosphate cement according to the present invention is characterized in that the raw slurry obtained by wet synthesis at a specific temperature is dried and then fired.

In the method for producing the third calcium phosphate cement of the present invention, the raw material components used in the wet synthesis may include a calcium supply material and a phosphorus supply material constituting the third calcium phosphate. , CaCl ₂ , Ca (N
O ₃ ) ₂ , Ca (OH) _{2 and the} like, and H ₃ PO ₄ , KH ₂ PO ₄ , (NH ₄ ) ₂ HPO ₄ , NH ₄ H ₂
PO _{4 and the} like can be preferably mentioned.

In the production method of the present invention, first, raw materials are wet-synthesized in order to obtain the raw material slurry. To perform the wet synthesis, for example, a raw material component containing the calcium feedstock and the phosphorus feedstock is dissolved in water,
After the aqueous solution is formed, the reaction can be easily carried out, for example, by reacting while controlling the water temperature of the aqueous solution to 15 ° C. or lower.
Since the reaction is an exothermic reaction, the temperature of the reaction system rises with the progress of the reaction. However, in order to obtain tribasic calcium phosphate having higher hydration activity, it is necessary to control the temperature of the reaction system to 15 ° C. or lower. is there. The lower limit of the reaction temperature is not particularly limited as long as the aqueous solution does not freeze.

Further, in the production method of the present invention, a desired tribasic calcium phosphate can be obtained by drying and calcining the obtained raw material slurry, and the drying is performed, for example, by a spray dryer. The drying can be carried out by a usual drying method such as spray drying using a drying method or drying with a dryer. In addition, the firing needs to be performed at 700 ° C. or higher in order to obtain a desired tribasic calcium phosphate. Specifically, for example, when obtaining α-type tricalcium phosphate, the calcination temperature is preferably 1200 ° C. or higher, and when obtaining β-type tricalcium phosphate, the calcination temperature is preferably 7 ° C.
When the temperature is set to 00 ° C. to 1050 ° C. to obtain a mixture of α-type calcium phosphate and β-type calcium triphosphate, 1
The temperature is preferably from 500 to 1200 ° C. At this time, if the firing temperature is lower than 700 ° C., only hydroxyapatite can be obtained, and tricalcium phosphate cannot be obtained. The firing time is preferably in the range of 1 to 10 hours.

When the tertiary calcium phosphate obtained by the production method of the present invention is used as a calcium phosphate cement raw material, it is preferably used after crushed into granules. In this case, the average particle size of the granules is preferably 5 μm or less. If the average particle size exceeds 5 μm, it takes a long time to cure the cement, and the initial strength is undesirably reduced.

It is particularly preferable to bake the dried slurry of the raw material slurry after press-molding the dried slurry, because the strength of the cement is further improved.

The hydraulic calcium phosphate cement of the present invention is characterized in that a mixture obtained by mixing the third calcium phosphate obtained by the above-mentioned production method with the second calcium phosphate and / or the first calcium phosphate is used as a main component of the powder. And

In the hydraulic calcium phosphate cement of the present invention, the second calcium phosphate and / or the first calcium phosphate used as a dust component is mixed with the third calcium phosphate.
Calcium phosphate is a component that reacts with the third calcium phosphate to generate octacalcium phosphate and hardens in the presence of water. As the dibasic calcium phosphate and the monobasic calcium phosphate used at this time, commercially available dibasic calcium phosphate dihydrate, monobasic calcium phosphate monohydrate and the like can be preferably mentioned.

As the above-mentioned tribasic calcium phosphate used in the hydraulic calcium phosphate cement of the present invention, α-type tribasic calcium phosphate and β-type tribasic calcium phosphate can be used alone, but in particular, in order to prevent long-term deterioration of cement strength. In addition, α-type tribasic calcium phosphate and β-type
It is preferred to use a mixture with calcium phosphate. The mixing ratio of the α-type tribasic calcium phosphate and the β-type tribasic calcium phosphate is preferably in the range of 100: 0 to 50:50 by weight. If the mixing ratio of the α-type tribasic calcium phosphate is less than 50% by weight, sufficient initial strength is not exhibited, which is not preferable. When a mixture of α-type tribasic calcium phosphate and β-type tribasic calcium phosphate is used as the third calcium phosphate, α-type tribasic calcium phosphate and β-type tribasic calcium phosphate, each of which may be obtained independently, may be mixed, In the above-mentioned production method, the tricalcium phosphate mixture obtained as a direct mixture may be used as it is. The α-type tribasic calcium phosphate obtained by the production method of the present invention has higher hydration activity and shorter cement hardening time than α-type tribasic calcium phosphate synthesized by a normal dry method. Further, the strength can be increased.

In the present invention, the mixing ratio of the tribasic calcium phosphate used as the powder component to the dibasic calcium phosphate and / or the monobasic calcium phosphate is Ca
The molar ratio of / P is preferably from 1.400 to 1.498. If the Ca / P molar ratio is outside the above range, the strength is undesirably reduced.

As the liquid agent used in the present invention, water alone is sufficient, but in order to further improve the operability,
A water-soluble polymer or a water-soluble polysaccharide may be added for use.

The mixing ratio of the powder material and the liquid material is preferably in the range of 3 to 1: 1 by weight. If the compounding ratio of the powder material is less than 1, the strength of the cured product decreases, and if it exceeds 3, the operability during kneading decreases, which is not preferable.

The hydraulic calcium phosphate cement of the present invention may further comprise, as necessary, an X-ray contrast agent such as barium sulfate, bismuth subcarbonate, and iodoform; an antibacterial agent such as iodoform and chlorhexidine; hydroxyapatite; Other ceramic powders having excellent biocompatibility such as alumina and zirconia can be further contained.

[0024]

According to the method for producing tribasic calcium phosphate of the present invention, the raw slurry obtained by wet synthesis with the temperature controlled to 15 ° C. or lower is dried and then calcined. A tricalcium phosphate having a higher hydration activity than calcium phosphate can be obtained.

The hydraulic calcium phosphate cement of the present invention uses, as a main component of the powder, the tertiary calcium phosphate obtained by the above-mentioned specific method, so that it has excellent biocompatibility and does not deteriorate in strength for a long period of time. Therefore, it is useful as a filling material for a bone defect and a bone cavity or a filling material for a tooth root canal.

[0026]

The present invention will be described in more detail with reference to the following examples, comparative examples and reference examples, but the present invention is not limited to these examples.

[0027]

REFERENCE EXAMPLES 1-4 1.5 l of water was charged into a 2 l beaker,
In each case, 3 mol of the calcium compound shown in Table 1 was charged and sufficiently stirred. Next, after dissolving 2 mol of each of the phosphorus compounds shown in Table 1 in 200 ml of water, the resulting aqueous solution was gradually added dropwise with stirring over 2 hours. At this time
The temperature of the aqueous solution in the car was controlled at 20 ° C. until the end of the reaction. After completion of the reaction, the mixture was allowed to stand for one day, and the whole amount was dried with a dryer.
Calcination was performed at 1,150 ° C. and 1000 ° C. for 3 hours to prepare tricalcium phosphate. Then, the tricalcium phosphate obtained using a ball mill was pulverized to an average particle size of 4 μm, and identified using an X-ray analyzer (trade name “RU-200”, manufactured by Rigaku Corporation). 1250 ° C
Is calcined α-type tricalcium phosphate,
What was calcined at 150 ° C. was a mixture of α-type tribasic calcium phosphate and β-type tribasic calcium phosphate.
What was calcined at ℃ was β-type tribasic calcium phosphate.

[0028]

[Table 1]

[0029]

Reference Example 5 A hydraulic calcium phosphate cement having the composition shown in Table 2 was prepared using the tricalcium phosphate obtained by firing at 1250 ° C. in Reference Example 3. Next, 100 parts by weight of water as a curing liquid was added to 175 parts by weight of the obtained hydraulic calcium phosphate cement and kneaded, and the curing time and the compressive strength of the cured cement were measured. At this time, the curing time was measured according to JIS T6604, and the compressive strength was measured at a loading rate of 1 mm / min while the cement (diameter 7 mm, length 14 mm) taken out after standing in an artificial body fluid for 1 day was wet. And measured under pressure. When measuring, a universal testing machine “1125” manufactured by Instron
Was used. Table 2 shows the results.

[0030]

Comparative Example 1 The setting time and compressive strength were measured in the same manner as in Reference Example 5, except that the powder component of the hydraulic calcium phosphate cement was changed to only tertiary calcium phosphate. Table 2 shows the results.

[0031]

Reference Example 6 344 g of dicalcium phosphate dihydrate (special grade, manufactured by Wako Pure Chemical Industries, Ltd.) was calcined at 550 ° C. for 3 hours to obtain 254 g of calcium pyrophosphate. Next, the obtained calcium pyrophosphate and calcium carbonate were mixed in an equimolar amount and calcined at 1250 ° C. to obtain α-type tribasic calcium phosphate. The obtained α-type tribasic calcium phosphate was pulverized using a ball mill to an average particle size of 4 μm.

[0032]

Comparative Example 2 The curing time and compressive strength were measured in the same manner as in Reference Example 5 except that the α-type tribasic calcium phosphate prepared in Reference Example 6 was used. Table 2 shows the results.

[0033]

[Table 2]

[0034]

[Examples 1-2 and Comparative Examples 3-4] Ca (OH) ₂ and H ₃
Using PO ₄ , the reaction temperatures were 1 ° C. (Example 1), 10 ° C. (Example 2), 20 ° C. (Comparative Example 1), 30 ° C., respectively.
° C (Comparative Example 2), and the firing temperature was 1250 ° C for 3 hours. The obtained α-type tribasic calcium phosphate and the second
Calcium phosphate dihydrate was mixed at a Ca / P molar ratio of 1.48 to prepare a hydraulic calcium phosphate cement. Using the obtained cement, the curing time and the compressive strength were measured in the same manner as in Reference Example 5. Table 3 shows the results
Shown in

[0035]

Comparative Example 5 An α-type tricalcium phosphate was prepared in the same manner as in Examples 1 and 2, except that the temperature of the reaction system was not controlled, and then a hydraulic calcium phosphate cement was prepared. Was measured. Table 3 shows the results. In this case, the temperature of the reaction system was 35 to 40 ° C.

[0036]

Comparative Example 6 The curing time and compressive strength were measured in the same manner as in Examples 1 and 2, except that the tribasic calcium phosphate obtained in Reference Example 6 was used. Table 3 shows the results.

[0037]

Examples 3 and 4 and Comparative Examples 7 and 8 After the raw material slurry was spray-dried with a spray dryer, 1000 kg / cm.
Except that calcined by pressing at a ^second pressure, Examples 1-2
The wet synthesis and the preparation of the cement were carried out in the same manner as described above, and the setting time and compressive strength were measured. Table 3 shows the results.

[0038]

[Table 3]

[0039]

Examples 5 to 7 Using Ca (OH) ₂ and H ₃ PO ₄ , the reaction temperature was set at 10 ° C., and the firing temperature was set at 100 ° C.
0 ° C. (Example 5), 1150 ° C. (Example 6), 1250
Reference Example 3 except that the mixture was baked at 3 ° C. (Example 7) for 3 hours.
In the same manner as described above, tribasic calcium phosphate was prepared. Table 4 shows the results.

[0040]

[Table 4]

[0041]

Examples 8 and 9 The tribasic calcium phosphates obtained in Examples 5 and 7 were mixed at the mixing ratio shown in Table 3, and the obtained tribasic calcium phosphate and dibasic calcium phosphate dihydrate were mixed with Ca / P The mixture was mixed at a molar ratio of 1.48 to prepare a hydraulic calcium phosphate cement (Example 8). In addition, a hydraulic calcium phosphate cement was similarly prepared using the third calcium phosphate obtained in Example 6 as it was (Example 9). The curing time and the compressive strength were measured in the same manner as in Reference Example 5. Table 5 shows the results.

[0042]

Comparative Example 9 An α-type tribasic calcium phosphate was prepared in the same manner as in Examples 1 and 2, except that the temperature of the reaction system was not controlled, and the curing time and compressive strength were measured. Table 5 shows the results
Shown in At this time, the temperature of the reaction system was 35 ° C.

[0043]

Comparative Example 10 The curing time and the compressive strength were measured in the same manner as in Examples 1 and 2, except that the α-type tribasic calcium phosphate obtained in Reference Example 6 was used. Table 5 shows the results.

[0044]

[Table 5]

──────────────────────────────────────────────────続 き Continuation of front page (56) References JP-A-63-100008 (JP, A) JP-A-64-37445 (JP, A) JP-A-3-69536 (JP, A) JP-A-58-58 161911 (JP, A) (58) Field surveyed (Int. Cl. ⁶ , DB name) C01B 25/32 C04B 12/02

Claims (2)

(57) [Claims] 1. A raw material slurry obtained by wet-synthesizing a raw material component containing a calcium supply material and orthophosphoric acid as a phosphorus supply material in an aqueous solution at a water temperature of 15 ° C. or less, and then drying, and then 700 ° C. or more. A method for producing tricalcium phosphate, characterized by baking. 2. A raw material slurry obtained by wet synthesizing a raw material component containing a calcium supply material and orthophosphoric acid as a phosphorus supply material in an aqueous solution having a water temperature of 15 ° C. or less, and then drying, and then 700 ° C. or more. Hydraulic calcium phosphate cement comprising a powder and a liquid containing a mixture of tribasic calcium phosphate obtained by calcining with a second calcium phosphate and / or a first calcium phosphate as a main component.