JP2002160948A - Calcium phosphate cement, its use and method of manufacture - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide rapidly hardening calcium phosphate cement. SOLUTION: The cement comprises calcium phosphate particles with a particle diameter of 0.05-100 μm having whiskers with width of 1-100 nm and length of 1-1,000 nm or microfine crystals on their surfaces, which are prepared by mixing calcium phosphate powder or particles with a wetting agent and controlling the growth of whiskers or microfine crystals on their surfaces.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a calcium phosphate cement, its use and its manufacturing method, and more particularly to a rapidly setting calcium phosphate cement for use in dental and bone prostheses, its composition and its manufacturing method.

[0002]

2. Description of the Related Art Calcium phos cement
Phage cement (hereinafter abbreviated as CPC) is widely used as an implant or filling material in tooth and bone prostheses, and its detailed technology can be found in many patent publications. For example, USP 4,
959,104; 5,092,888; 5,180,426; 5,262,166; 5,336,26
4; 5,525,148; 5,053,212; 5,149,368; 5,342,441; 5,5
03,164; 5,542,973; 5,545,254; 5,695,729 and 5,814,
681 and the like.

[0003] In general, the prior art calcium phosphate cements have the following disadvantages: 1) the relatively poor biological activity required of the additives; 2) the production process is complex; 3).
Improper and difficult to adjust the curing or operating time of CPC; 4) inability to cure to the desired shape in water, blood or body fluids; and 5) low initiation force after CPC curing.

[0004]

It is an object of the present invention to provide a calcium phosphate cement.

It is another object of the present invention to provide a calcium phosphate cement comprising particles having whiskers or fine crystals on the surface of the particles.

[0006] Another object of the present invention is to provide a method for producing calcium phosphate cement.

It is another object of the present invention to provide a composition for treating bone or tooth defects in a patient using calcium phosphate cement.

[0008]

Means for Solving the Problems In order to achieve the above object, the calcium phosphate cement produced according to the present invention is a calcium phosphate cement having a particle diameter of 0.05 to 100 μm. Width 1-1
It has whiskers or fine crystals of 00 nm, length 1-1000 nm.

By adjusting the diameter of the calcium phosphate cement particles, the width and / or the length of the whiskers or microcrystals, the inventors of the present invention can adjust the calcium phosphate cement of the present invention to meet the needs of various purposes. Operating time and / or
Alternatively, the setting time can be adjusted, and the calcium phosphate cement of the present invention sets quickly and does not disperse in water or an aqueous solution.

An object of the present invention is to provide a surface having a width of 1 to 100 n.
m, a calcium phosphate cement characterized by having a calcium phosphate cement of calcium phosphate particles having a particle size of 0.05 to 100 μm with whiskers or fine crystals having a length of 1 to 1000 nm.

Another object of the present invention is to mix calcium phosphate powder or small pieces with a wetting agent and control the growth of whiskers or fine crystals on the surface of the calcium phosphate powder or small pieces by a control treatment. And a method for producing a calcium phosphate cement.

It is another object of the present invention to provide (i) a calcium phosphate cement of calcium phosphate particles having whiskers or fine crystals of 1 to 100 nm in width and 1 to 1000 nm in length and having a particle diameter of 0.2 to 80 μm. And (i
i) a dental filling or bone prosthesis, which comprises an aqueous solution containing a hardening accelerator.

[0013]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The preferred method of producing the calcium phosphate cement of the present invention includes mixing calcium phosphate powder or small pieces with a wetting agent to reduce the growth of whiskers or fine crystals on the surface of the calcium phosphate powder or small pieces. Control by control processing is included.

The calcium phosphate applied to the calcium phosphate powder or small pieces of the present invention is all known calcium phosphates, such as calcium dihydrogen phosphate, calcium dihydrogen phosphate hydrate, calcium acid pyrophosphate, and anhydrous hydrogen phosphate. Calcium, calcium hydrogen phosphate hydrate, calcium pyrophosphate, calcium triphosphate, calcium polyphosphate, calcium metaphosphate, anhydrous calcium triphosphate, calcium triphosphate hydrate, apatite, hydroxyapatite, mixtures thereof and their adducts Is mentioned. In other words, the shape of calcium phosphate powder and small pieces is not limited, and may be spherical or irregular, and their crystal structure may be single crystal, polycrystal, mixed crystal, semi-crystal or amorphous. Good.

In the method for producing calcium phosphate cement, preferably, the product obtained by the further control treatment is pulverized so that the diameter of calcium phosphate particles is 0.05 to 100 μm (grin
d), a step of setting the width of the whisker or fine crystal to 1 to 100 nm and the length to 1 to 1000 nm.

The control treatment may be a vacuum treatment, an organic solvent treatment, a microwave treatment, a heat treatment or another treatment, which can control the growth of whiskers or fine crystals on the surface of the calcium phosphate powder or small pieces.

The humectant is used for humidifying calcium phosphate powder or small pieces, and is preferably a dilute aqueous solution containing phosphoric acid or phosphate. The amount of humectant mixed with the calcium phosphate powder or flakes should generally substantially humidify all calcium phosphate powder or flakes, but if the control treatment is an organic solvent treatment, water It is not always necessary because the humectant and the organic solvent are added to the wetting agent and the powder or small pieces of calcium phosphate to make the paste used in the next step.

Preferably, the wetting agent converts the phosphoric acid or phosphate from 0.02 mM to 3000 mM, preferably from 0.05 to 3000 mM.
2000 mM, more preferably 0.1 mM to 1000 m
It is a diluted aqueous solution containing the range of M.

In the method for producing a calcium phosphate cement of the present invention, the calcium phosphate powder or small pieces are preferably immersed in a dilute aqueous solution containing 0.1 mM to 1000 mM of phosphoric acid or phosphate, and then the following steps are performed: ) 30-1600 powder or small pieces of calcium phosphate obtained by the immersion.
(B) a vacuum treatment of drying the calcium phosphate powder or small pieces obtained by immersion in a vacuum, or (c) a calcium phosphate powder or small piece of the immersion obtained. Microwave treatment by heating with microwaves. Preferably, before the treatment (a), (b) or (c), the calcium phosphate powder or small pieces obtained by the immersion are thoroughly mixed to form a uniform mixture.

Further, in the method for producing a calcium phosphate cement of the present invention, the calcium phosphate powder or small piece is mixed with a dilute aqueous solution containing 0.1 mM to 1000 mM of phosphoric acid or phosphate, and the calcium phosphate powder or small piece is wetted. An organic solvent treatment of mixing the mixture with the agent with a hydratable organic solvent may be performed, and the resulting mixture may be dried in vacuo. Preferably, the organic solvent treatment is performed with stirring. More preferably, before the organic solvent treatment is performed, a dilute aqueous solution containing 0.1 mM to 1000 mM of the phosphoric acid or the phosphate is sufficiently mixed with calcium phosphate powder or small pieces. .

[0021] Preferably, the calcium phosphate particles of the calcium phosphate cement of the present invention have a diameter of 0.2 to 80.
μm, more preferably 0.5 to 50 μm.

The width of the whisker is the average value of the cross-sectional diameter of the whisker.
Average value of 0%, shorter than the other 70%. The length of the microcrystal is the average of the last 30% of the diameter of the microcrystal and is longer than the other 70%.

Preferably, the whiskers or fine crystals have a width of 2 to 70 nm and a length of 5 to 800 nm, more preferably a length of 10 to 700 nm.

Preferably, in the calcium phosphate particles,
The molar ratio of calcium to phosphoric acid is 0.5-2.5, more preferably 0.8-2.3, most preferably 1.0-2.
2 range.

The calcium phosphate cement of the present invention is bio-acceptable, the paste made therefrom is non-dispersible in water, the operating time is a few minutes to a few hours, and the setting time is a few minutes to a few hours. . Thus, the calcium phosphate cements of the present invention should be in paste and contact with water, blood or body fluids and are very suitable as implant or filling material for tooth or bone prostheses. In particular, the calcium phosphate cement of the present invention is used for implanting or filling a prosthesis directly into a bone defect or cavity.

Further, the present invention relates to (i) a method in which the surface has a width of 1 to 10
A tooth comprising: a calcium phosphate cement of calcium phosphate particles having a particle diameter of 0.2 to 80 μm having whiskers or fine crystals having a length of 0 nm and a length of 1 to 1000 nm; and (ii) an aqueous solution containing a hardening accelerator. Or a composition for bone prosthesis.

Although the mixing ratio of the calcium phosphate cement of the present invention to the aqueous solution containing a hardening accelerator is not specified, the amount of the aqueous solution containing the hardening accelerator is sufficiently mixed to substantially humidify the calcium phosphate cement of the present invention. Should. When the paste is injected or implanted in a bone defect or cavity, saliva or body fluids provide additional water. Of course, the content of the curing accelerator in the aqueous solution containing the curing accelerator should be adjusted higher than the aqueous solution containing the curing accelerator to be mixed. In the composition of the present invention, the ratio of the component (i) to the component (ii) is such that the ratio of the component (ii) is 0.1 to 1 g of the component (i).
1 ml to 10 ml, preferably 0.15 ml to 1.0 m
A range of 1 is desirable. When the amounts of both components are within this range, a paste can be formed because the amount of component (ii) is sufficient to wet component (i). However, when the amount of the component (ii) exceeds this range, the paste is not formed, but becomes a suspension, which is not preferable.

In the composition of the present invention, the calcium phosphate cement further contains a growth factor, a bone morphological protein or a pharmaceutical carrier, or the aqueous solution containing the hardening accelerator further contains a growth factor, a bone morphological protein or a pharmaceutical carrier.

The aqueous solution containing the curing accelerator is an aqueous solution containing all known compounds or compositions capable of solidifying calcium phosphate, such as phosphates, calcium salts and fluorides, and contains phosphate ions, calcium ions, fluorine ions, or phosphate ions. An aqueous solution containing ions and fluorine ions as a curing accelerator.

The content of the curing accelerator in the aqueous solution containing the curing accelerator is not particularly limited, but is preferably 1 mM to 3M, particularly preferably 10 mM to 1M.

The present invention further provides a method for treating a patient having a bone or tooth defect using the above composition. To this end, the calcium phosphate cement of the present invention is mixed with an aqueous solution containing a hardening accelerator to form a paste, and the paste is placed in a bone defect or cavity of the patient, or the paste is molded, and the resulting paste is formed. The paste is embedded in the bone defect or cavity of the patient.

[0032]

The present invention will now be described more specifically with reference to examples. However, this is not intended to limit the invention to only those embodiments.

Example 1 Heat Treatment 5 g of Ca (H ₂
PO ₄ ) ₂ .H ₂ O powder and 1.6 ml of a 25 mM phosphoric acid aqueous solution were mixed, stirred for 1 minute, and placed in an oven at 50 ° C. for 15 minutes.
After drying for minutes, the resulting dry mixture was removed from the oven and ground with a machine for 20 minutes until it became fine. 1 g of fine particles and 0.4 ml of an aqueous phosphate solution (1.0 M, pH =
6.0), and the resulting paste was tested every 30 seconds to determine the run time and cure time. Curing time is the time required to insert a 1 mm diameter pin to a depth of 1 mm under a load of 1/4 lb into the surface of the paste, and operating time indicates the time until the viscosity of the paste can no longer be stirred. The operation time of the paste of this example is 30 minutes, and the curing time is 1 hour.

Immediately after molding, the paste was immersed in a relatively large amount of deionized water, and it was observed that the paste did not disperse in deionized water.

(Example 2: Vacuum treatment) 5 g of CaHPO
₄ Mix (DCPA) powder with 1.2 ml of 25 mM phosphoric acid aqueous solution, stir for 1 minute, and vacuum at −100 Pa for 30 minutes.
And dry the resulting dry mixture for 20 minutes until fine particles are obtained.
Crushed with a minute machine. One gram of the microparticles was mixed with 0.4 ml of an aqueous phosphate solution (1.0 M, pH = 6.0), and the resulting paste was tested every 30 seconds to determine the operating and curing times. The operation time of the paste of this example was 20.5.
Minutes and the curing time is 24 minutes.

Immediately after molding, the paste was immersed in a relatively large amount of deionized water, and it was observed that the paste did not disperse in deionized water.

Example 3 Treatment with Organic Solvent 5 g of CaH
PO ₄ (DCPA) powder and 1.6 ml of a 25 mM phosphoric acid aqueous solution were mixed, stirred for 1 minute, added with 1.6 ml of acetone, stirred to form a paste, and then dried under a vacuum of −100 Pa for 1 hour. The obtained dry mixture was pulverized by a machine for 20 minutes until it became fine particles. 1g of fine particles and 0.4ml
Was mixed with an aqueous phosphate solution (1.0 M, pH = 6.0), and the resulting paste was tested every 30 seconds to determine the operating and curing times. The operation time of the paste of this example is 20.0 minutes, and the curing time is 22.0 minutes.

Immediately after molding, the paste was immersed in a relatively large amount of deionized water, and it was observed that the paste did not disperse in deionized water.

Example 4: Microwave treatment Ca
HPO ₄ (DCPA) and Ca ₄ (PO ₄ ) ₂ O (TTCP)
3 g of a 1: 1 molar ratio mixed powder and 2.0 ml of a 25 mM phosphoric acid aqueous solution were mixed, stirred for 5 minutes, and heated in a microwave oven at a low output for 5 minutes. Crushed with a minute machine. 1g of fine particles and 0.4
2 ml of an aqueous phosphate solution (1.0 M, pH = 6.0) were mixed and the resulting paste was tested every 30 seconds to determine the operating time and the setting time. The operation time of the paste of this example is 2.0 minutes, and the curing time is 4.5 minutes.

Immediately after molding, the paste was immersed in a relatively large amount of deionized water, and it was observed that the paste did not disperse in deionized water.

Example 5 Heat Treatment CaHPO ₄ (D
CPA) and Ca ₄ (PO ₄ ) ₂ O (TTCP) were mixed with 5 g of a 1: 1 molar ratio mixed powder and 1.6 ml of 25 mM phosphoric acid aqueous solution, stirred for 1 minute, and heated in a 500 ° C. high temperature oven for 5 minutes. Then, the obtained dry mixture was pulverized by a machine for 20 minutes until it became fine particles. One gram of the microparticles was mixed with 0.4 ml of an aqueous phosphate solution (1.0 M, pH = 6.0), and the resulting paste was tested every 30 seconds to determine the operating and curing times. The operation time of the paste of this embodiment is as follows.
At 5 minutes, the cure time is 2.5 minutes.

Immediately after molding, the paste was immersed in a relatively large amount of deionized water, and it was observed that the paste did not disperse in deionized water.

Example 6 Heat Treatment CaHPO ₄ (D
CPA) and Ca ₄ (PO ₄ ) ₂ O (TTCP) were mixed with 5 g of a 1: 1 molar ratio mixed powder and 1.6 ml of a 25 mM phosphoric acid aqueous solution, stirred for 1 minute, and heated in a 1000 ° C. high temperature oven for 1 minute. Then, the obtained dry mixture was pulverized by a machine for 20 minutes until it became fine particles. 1 g of fine particles and 0.4 ml of a phosphate aqueous solution (1.0 M, pH = 6.0) were mixed,
The resulting paste was tested every 30 seconds and the run time and cure time were measured. The operation time of the paste of this example is 3
In one minute, the curing time is 35 minutes.

(Examples 7-11) Ca in Example 1
(H ₂ PO ₄ ) ₂ · H ₂ O is converted to CaHPO ₄ (DCPA) and C
The same process as in Example 1 was performed, except that 5 g of a 1: 1 molar ratio mixed powder of a ₄ (PO ₄ ) ₂ O (TTCP) was used, and the 25 mM phosphoric acid aqueous solution was replaced with a dilute phosphoric acid aqueous solution having a pH of 1.96. Table 1 shows the conditions and performance of the heat treatment.

Comparative Example 1 1 g of a mixed powder of CaHPO ₄ (DCPA) and Ca ₄ (PO ₄ ) ₂ O (TTCP) at a molar ratio of 1: 1 was mixed with 0.4 ml of an aqueous solution of dilute phosphoric acid of pH 1.96 to obtain a mixture. The resulting paste was tested every 30 seconds and the run time and cure time were measured. The paste of this comparative example did not cure within one hour. The performance is as shown in Table 1.

(Example 12) CaHP in Example 2
O_Four(DCPA) to CaHPO_Four(DCPA) and Ca
_Four(PO_Four)_TwoO (TTCP) 1: 1 molar ratio mixed powder
Alternatively, 25 mM phosphoric acid aqueous solution is diluted phosphoric acid aqueous solution of pH 1.96.
The same steps as in Example 2 are performed instead of the liquid. The performance is shown in Table 1.
It is as follows.

Example 13 CaHP in Example 3
O_Four(DCPA) to CaHPO_Four(DCPA) and Ca
_Four(PO_Four)_TwoO (TTCP) 1: 1 molar ratio mixed powder
Alternatively, 25 mM phosphoric acid aqueous solution is diluted phosphoric acid aqueous solution of pH 1.96.
The same steps as in Example 3 are performed instead of the liquid. Its performance is shown in Table 1.
It is on the street.

Example 14 25 mM in Example 4
The same process as in Example 4 is performed, except that the phosphoric acid aqueous solution is replaced with a dilute phosphoric acid aqueous solution having a pH of 1.96. The performance is as shown in Table 1.

[0049]

[Table 1]

The pastes prepared in Comparative Example 1 and Example 7 were poured into water from a syringe 3, 10 and 30 seconds after the preparation. The results are shown in FIGS.
It is as follows. 5 and 6, the paste manufactured in Comparative Example 1 is dispersed in water. In contrast, the paste prepared in Example 7 does not disperse in water (see FIGS. 8-10).

Two pillars respectively formed from the pastes of Comparative Example 1 and Example 7 were left in water. Figures 11 to 1
3 is a photograph of the column after immersion in water for 5, 20 and 60 seconds. The left column formed from the paste of Comparative Example 1 collapsed, but the right column formed from the paste of Example 7 was almost unchanged. Absent.

Summarizing the results of FIGS. 5 to 13, the calcium phosphate cement of the invention can be implanted directly into a deformed tooth or bone cavity after injection or molding into a block.

Two samples of the calcium phosphate cement prepared in Example 7 were observed with a transmission electron microscope (TEM). FIGS. 14 and 15 show the calcium phosphate cements having various diameters of the calcium phosphate cement. Indicates that whiskers are present on the particles.

FIG. 1 shows the particle size distribution of the calcium phosphate cement produced in Example 6 measured by a particle size analyzer (Sald-2001, Shimadzu). From the curve in FIG. 1, the particle size of the calcium phosphate cement produced in Example 6 was about 0.4.
7 to 93.49 μm. FIG. 2 shows a scanning electron microscope (SE) of the calcium phosphate cement manufactured in Example 6.
M) A photograph is shown. Further, the length and width of the whiskers or microcrystals on the surface of the calcium phosphate cement manufactured in Example 6 were determined by TEM (JXA-840, JEOL Co.,
Japan) and the results are shown in FIGS.
The length and width of the whiskers or microcrystals on the surface of the calcium phosphate cement produced in Example 6 are 1 to 625 nm and 1 to 65 nm, respectively.

(Examples 15-19) The same steps as in Example 7 were performed using the calcium phosphate powder and the wet solution shown in Table 2. The performance is as shown in Table 2.

[0056]

[Table 2]

* TCP: tricalcium phosphate anhydrous, TTCP + DCPA: powder mixed in a 1: 1 molar ratio of TTCP and DCPA, TTCP + DCPA + TCP: 1: 1 of TTCP + DCPA and TCP
Mass ratio mixed powder, DCPA + TCP: 1: 2 molar ratio mixed powder of DCPA and TCP.

Comparative Example 2-6 The same steps as in Comparative Example 1 were performed using the calcium phosphate powder and the wet solution shown in Table 2. The performance is as shown in Table 2.

(Examples 20-31) The same steps as in Example 7 were carried out using wet solutions having various pH values shown in Table 3. The performance is as shown in Table 3.

(Comparative Examples 7-14) The same steps as in Comparative Example 1 were carried out using the wet solutions having various pHs listed in Table 3. The performance is as shown in Table 3.

[0061]

[Table 3]

[0062]

According to the present invention, it is possible to provide a calcium phosphate cement which hardens rapidly and is not dispersed in water or an aqueous solution. In addition, the operating time and setting time of the cement can be adjusted by adjusting the diameter of the calcium phosphate cement particles, the width and length of the whiskers or microcrystals.

According to the method of the present invention, a calcium phosphate cement having the above properties can be obtained by a simple method.

According to the composition of the present invention, a composition for filling teeth or for prosthesis of bone can be provided.

[Brief description of the drawings]

FIG. 1 is a graph in which the particle distribution of calcium phosphate cement (CPC) manufactured according to Example 6 of the present invention is plotted as normalized particle amount (%) versus particle size (μm).

FIG. 2 is an electron micrograph (SEM) of a calcium phosphate cement (CPC) manufactured according to Example 6 of the present invention.
It is.

FIG. 3 shows a transmission electron microscope (TEM) of a calcium phosphate cement (CPC) manufactured according to Example 6 of the present invention.
4 is a graph showing the distribution of the length of whiskers or fine crystals on the surface of calcium phosphate cement particles directly measured by the method shown in FIG.

FIG. 4 shows a transmission electron microscope (TEM) of a calcium phosphate cement (CPC) manufactured according to Example 6 of the present invention.
5 is a graph showing the distribution of the width of whiskers or fine crystals on the surface of calcium phosphate cement particles directly measured by the method shown in FIG.

FIG. 5 shows a photograph of a conventional CPC paste injected into water with a syringe 3 seconds after the formation of the conventional CPC paste.

FIG. 6 shows a photograph of a conventional CPC paste injected into water with a syringe 10 seconds after the formation of the conventional CPC paste.

FIG. 7 shows a photograph of a conventional CPC paste injected into water with a syringe 30 seconds after the formation of the conventional CPC paste.

FIG. 8 shows a photograph of the CPC paste of the present invention injected into water with a syringe 3 seconds after the CPC paste was formed in Example 7 of the present invention.

FIG. 9 shows a photograph of the CPC paste of the present invention injected into water with a syringe 10 seconds after the CPC paste was formed in Example 7 of the present invention.

FIG. 10 shows the CPC of the present invention injected into water with a syringe 30 seconds after the CPC paste is formed in Example 7 of the present invention.
A photograph of the paste is shown.

FIG. 11 shows a conventional CPC paste and Example 7 of the present invention.
5 shows a photograph 5 seconds after immersing the two pillars each formed with the CPC paste manufactured in Step 2 in water.

FIG. 12 shows a conventional CPC paste and Example 7 of the present invention.
The photograph after 20 seconds of immersing the two pillars each formed with the CPC paste manufactured in step 2 in water is shown.

FIG. 13 shows a conventional CPC paste and Example 7 of the present invention.
A photograph 60 seconds after immersing the two pillars each formed with the CPC paste manufactured in step 2 in water.

FIG. 14 shows a TEM micrograph of the calcium phosphate cement of the present invention produced in Example 7.

FIG. 15 shows a TEM micrograph of the calcium phosphate cement of the present invention produced in Example 7.

 ──────────────────────────────────────────────────続 き Continued on front page (71) Applicant 500486106 911 Tower Rd. , Winnetka, Illinois 60093, U.S.A. S. A. (71) Applicant 500486117 91 Pineview Rd. , Carb online, Illinois 62901, U.S.A. S. A. (72) Inventor Zhu Jianping, Pinview Road 91, Carbondale, Illinois, 62901, United States of America 91 (72) Inventor Chen Wenchang Return Jin, Tainan County, Taiwan No.20, Nakayama Road 720 Alley 20 F Term (Reference) 4C081 AB04 AC04 CD112 CD27 CF011 EA01 EA11 4C089 AA06 BA16 CA06 4G012 PB13

Claims (31)

[Claims] 1. A surface having a width of 1 to 100 nm and a length of 1 to 10
The particle diameter of a whisker or fine crystal having a diameter of 00 nm is 0.1 mm.
A calcium phosphate cement comprising calcium phosphate cement of calcium phosphate particles having a particle size of from 0.5 to 100 μm. 2. The calcium phosphate particles having a particle size of 0.1.
The calcium phosphate cement according to claim 1, which has a thickness of 2 to 80 µm. 3. The whisker or the fine crystal has a width of 2 to 70.
The calcium phosphate cement according to claim 1, which has a length of 5 to 800 nm. 4. The calcium phosphate particles having a particle size of 0.1.
The calcium phosphate cement according to claim 3, which has a thickness of 5 to 50 m. 5. The whisker or the fine crystal has a length of 10 to 10.
The calcium phosphate cement according to claim 4, having a thickness of 700 nm. 6. The calcium phosphate particles according to claim 3, wherein the molar ratio of calcium to phosphoric acid is 0.5 to 2.5.
6. The calcium phosphate cement according to 4 or 5. 7. The calcium phosphate cement according to claim 4, wherein a molar ratio of calcium to phosphoric acid in the calcium phosphate particles is 0.8 to 2.3. 8. The calcium phosphate cement according to claim 4, wherein the molar ratio of calcium to phosphoric acid in the calcium phosphate particles is 1.0 to 2.2. 9. (i) A surface having a width of 1 to 100 nm and a length of 1
A dental phosphate filling or bone, comprising: a calcium phosphate cement of calcium phosphate particles having a particle diameter of 0.2 to 80 µm having whiskers or fine crystals having a particle diameter of 0.2 to 80 nm; and (ii) an aqueous solution containing a hardening accelerator. Composition for prosthesis. 10. The composition according to claim 9, wherein the aqueous solution containing the curing accelerator is an aqueous solution containing phosphate ions, calcium ions, fluorine ions, or phosphate ions and fluorine ions as curing accelerators. 11. The composition according to claim 10, wherein the content of the curing accelerator in the aqueous solution containing the curing accelerator is 1 mM to 3M. 12. The composition according to claim 11, wherein the content of the curing accelerator in the aqueous solution containing the curing accelerator is 10 mM to 1M. 13. A particle having a whisker or a fine crystal having a width of 2 to 70 nm and a length of 5 to 800 nm on the surface of the calcium phosphate particles, having a particle diameter of 0.2 to 80 μm.
A composition as described. 14. The composition according to claim 13, wherein said calcium phosphate particles have whiskers or fine crystals having a length of 10 to 700 nm on the surface thereof and a particle size of 0.5 to 50 μm. 15. The calcium phosphate particles according to claim 1, wherein the molar ratio of calcium to phosphoric acid is 0.5 to 2.5.
15. The composition according to 3 or 14. 16. The calcium phosphate particles according to claim 1, wherein the molar ratio of calcium to phosphoric acid is 0.8 to 2.3.
A composition according to claim 5. 17. The calcium phosphate particles according to claim 1, wherein the molar ratio of calcium to phosphoric acid is 1.0 to 2.2.
6. The composition according to 6. 18. A calcium phosphate cement, comprising mixing calcium phosphate powder or small pieces with a wetting agent and controlling the growth of whiskers or fine crystals on the surface of the calcium phosphate powder or small pieces by a control treatment. Method. 19. A surface having a width of 1 to 100 nm and a length of 1 to 1
The method according to claim 18, wherein the calcium phosphate particles having 000 nm whiskers or fine crystals have a particle size of 0.05 to 100 µm. 20. A surface having a width of 2 to 70 nm and a length of 5 to 80 nm.
20. The method according to claim 19, wherein the calcium phosphate particles having whiskers or fine crystals of 0 nm have a particle size of 0.2 to 80 [mu] m. 21. The method according to claim 20, wherein the calcium phosphate particles having whiskers or fine crystals having a length of 10 to 700 nm on the surface have a particle size of 0.5 to 50 μm. 22. The humectant as claimed in claim 1, wherein the humectant is phosphoric acid or phosphate.
The production method according to claim 18, which is an aqueous solution containing 2 to 3000 mM. 23. The humectant may contain phosphoric acid or phosphate in an amount of 0.0
The production method according to claim 22, which is an aqueous solution containing 5-2000 mM. 24. The humectant as claimed in claim 1, wherein the humectant is phosphoric acid or phosphate.
24. The production method according to claim 23, which is an aqueous solution containing up to 1000 mM. 25. The control process is a vacuum process, an organic solvent process, a microwave process, or a heat process.
The method according to 8, 22, 23 or 24. 26. The calcium phosphate powder or small piece is immersed in a wetting agent, and the control treatment is a heat treatment of drying the calcium phosphate powder or small piece obtained by the immersion at a temperature in the range of 30 to 1600 ° C. The method according to claim 25. 27. The production method according to claim 25, wherein the calcium phosphate powder or small pieces are immersed in a wetting agent, and the control treatment is a vacuum treatment of drying the calcium phosphate powder or small pieces obtained by the immersion in a vacuum. . 28. The method according to claim 25, wherein the calcium phosphate powder or the small piece is immersed in a wetting agent, and the control treatment is a microwave treatment in which the calcium phosphate powder or the small piece obtained by the immersion is heated with a microwave. Production method. 29. The method according to claim 25, wherein the control treatment is an organic solvent treatment in which a mixture of calcium phosphate powder or small pieces and a wetting agent is mixed with a hydratable organic solvent and dried under vacuum. 30. The calcium phosphate particles wherein the molar ratio of calcium to phosphoric acid is 0.5 to 2.5.
9. The production method according to 9. 31. The composition according to claim 9, wherein the calcium phosphate cement further comprises a growth factor, a bone morphological protein or a pharmaceutical carrier.