JPH0312317A - Device for producing hydroxyapatite fine grain - Google Patents

Abstract

PURPOSE:To control the diameter distribution of hydroxyapatite fine grains in a narrow range by connecting a formation reaction tank and an ageing tank with a connecting pipe and growing the grains under the conditions where the variations in the temp. of the soln. are minimized. CONSTITUTION:A heating mechanism 3 and a pH regulating mechanism 10 are provided in a storage tank 1 for water and/or a hydrophilic org. solvent. The storage tank 1 consists of the formation reaction tank 1a and the ageing tank 1b, and both tanks 1a and 1b are connected with the connecting pipe 5. Meanwhile, a non-phosphate type reactive Ca compd. and a non-Ca salt type reactive oxide of phosphorous are dissolved in the water and/or org. solvent kept at <=50 deg.C to prepare a raw soln. The raw soln. is dripped into the storage tank 1 through the feed pipes 7 and 7, and the Ca/P is specified.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to an apparatus for producing hydroxyapatite fine particles, and more particularly to an apparatus for producing single-phase, fine, high-purity hydroxyapatite fine particles with good crystallinity. It is something.

[Prior art] CaOPz Os-based apatite has been developed as a biomaterial, and among them, hydroxyapatite (hereinafter referred to as HA) has been developed as a biomaterial.
P) has the same composition as the material that forms bones in the human body, and when implanted in a living body, it has good compatibility with the living body and has good bonding properties with living bone, so it is used as an artificial bone or artificial tooth. It is used as a material such as In addition, affinity with proteins and HAP
Utilizing its own ion exchange ability, it is also used in chromatography packing materials and ion exchange materials.

As for the production method of HAP, ■Wet method: Ca salt aqueous solution and phosphate aqueous solution are reacted to produce C
A method of obtaining microcrystalline calcium phosphate with aHPO4.40 to 1.67 and further reacting it with a specific calcium compound to convert it into the desired HAP, ■Hydrothermal synthesis method: Japanese Patent Publication No. 59-51485 CaHP as disclosed
O4・2H, O (or CaHPO4) to Ca(OH)2
or OCP [Caa H2(PO4)
6 ・A method for producing crystalline HAP with a dense crystal structure by adding a Ca compound to 5H201 and reacting it in an autoclave under hydrothermal conditions of 200 to 400°C and 15 to 200 atm. ■Dry synthesis method: Japanese Patent Publication No. 1983- Caa H2(PO<)s・5Hz O disclosed in 51485
There is a method in which crystalline HAP with a dense crystal structure is produced by adding a compound and causing a solid phase reaction at 1000 to 1300°C.

However, in method (2), the reaction rate is high and the product is colloidal, making it difficult to handle and operate.
The reproducibility of Ca/P is poor, and produced phases other than HAP are mixed in, and unreacted phases remain. Method (2) requires high temperature and high pressure, which increases equipment costs and has low production efficiency. In addition, although it can be said to be a good method for obtaining large HAP particles, it is difficult to obtain fine particles. Method (2) requires high temperature and long time to complete the reaction. Also, ■
In the method of (1) and (2), pure CaH is
PO4・2H20 (or CaHPO,) and CaH2(P
It is essential to obtain O4)6.5H20.

Furthermore, in the case of molding powder and solidifying it by firing, if it is desired to increase the density of the molding, it is desirable that the particle size of the powder be as fine as possible and that the particle size distribution be narrow. The obtained HAP is a coarse particle with a particle size of several micrometers to 10 micrometers or more, and when the size of the -forming particles is this large, the filling rate becomes low and it is difficult to increase the density. If an attempt is made to reduce the particle size, the crystallinity deteriorates, and since it contains a large amount of water, the shrinkage rate during firing of the dense compact becomes large and unstable.

Therefore, Kideto developed a method to produce fine-grained HAP with good crystallinity using a HAP vehicle phase without requiring harsh conditions or using expensive equipment, and also to control Ca/P with good reproducibility. We have investigated a method for manufacturing HAP that can be used to produce HAP, and have previously filed Japanese Patent Application No. 326516/1983.

FIG. 4 is an explanatory cross-sectional view showing a HAP@ particle manufacturing apparatus used in the above method. Water and/or a hydrophilic organic solvent is stored in a storage tank 1, and a heater 3 and pH adjustment piping 10 are connected to the storage tank 1 to maintain the temperature at 70° C. or higher and the pH at 4 or higher (preferably 8 to 11). Roughly connect the raw material supply pipes 7, 7 to the storage tank 1, and connect the raw material supply pipes 7 to the storage tank 1.
．． 7, a non-phosphate type reactive Ca compound and a non-Ca salt type reactive oxygen acid compound of phosphorus were dissolved in water and/or a hydrophilic organic solvent at a temperature below 50 °C so as to have a predetermined Ca/P. It is configured so that the raw material solution is dropped into the storage tank 1. Note that the reference numeral 6 indicates a stirrer.

[Problems to be Solved by the Invention] By the way, when the raw material solution is supplied dropwise into the storage tank 1 in the above manufacturing apparatus, the pH of the solvent in the storage tank 1 becomes very unstable due to the difference in pH between the raw material solution and the solvent. , and it fluctuates widely. Therefore, the above device is configured to inject the pH adjustment liquid through the pH adjustment pipe 10 in order to suppress this fluctuation, but it is not possible to keep the solvent pH in the storage tank 1 uniform even with the stirrer 6. This is difficult, and in actual operation, pH fluctuations inevitably increase in the vicinity of the raw material supply pipe 7 or the pH adjustment pipe 10. In particular, this tendency becomes even more remarkable when the capacity of the storage tank 1 is increased in order to minimize temperature changes.

Furthermore, regarding the temperature of the solvent in the storage tank 1, raw material solutions of different temperatures are mixed, which causes temperature fluctuations and non-uniformity in temperature distribution throughout the storage tank 1.

HAP is affected by the pH fluctuations and temperature fluctuations mentioned above.
The environment in which HAP is produced is non-uniform and changes from time to time, resulting in large variations in the particle size and non-uniform shape of the HAP particles produced.

Therefore, the present inventor conducted extensive research and completed the present invention with the aim of providing an apparatus that can produce HAP fine particles with little variation in particle size and uniform shape.

[Means for Solving the Problems] In the present invention, which has achieved the above object, the storage tank is composed of a production reaction tank and an aging tank, and a supply pipe for supplying the raw material solution is connected to the production reaction tank. In addition, the gist is that the production reaction tank and the ripening tank are connected by a connecting pipe.

[Operations and Examples] FIG. 1 is a cross-sectional explanatory diagram showing a typical example of the present invention. The storage tank 1 is composed of a production reaction tank 1a and an aging tank 1b.The two tanks 1a and 1b are connected by a connecting pipe 5, and the solution in the production reaction tank 1a is pumped by a liquid feeding pump 5a provided in the connecting pipe 5. 2a into the solution 2b on the aging tank 1b side. Note that a raw material supply pipe 7.7 is connected to the production reaction tank 1a, and both tanks 1a.

1b is provided with a pH adjusting pipe 10.10 and a stirrer 6.6, respectively. The stirrer 6 in the aging tank 1b may be replaced with a stirring disk shown by a broken line. Also, the production reaction tank 1a
A heater 3 is provided on the wall of the ripening 4'11b, and is configured to keep the solution temperature in the tank constant.

The production of HAP fine particles using the above apparatus is carried out as described below.

First, non-phosphate reactive Ca compounds and non-Ca salt-type reactive oxygen acid compounds are soluble in water or woody organic solvents.For example, as non-phosphate reactive Ca compounds, Ca C12゜Ca (N Os)z, c
a (HCOO)2゜Ca CCHs Coo)2
, Ca(OH)2.

Non-limiting examples include CaCO3, Ca-alkoxides such as calcium dimethoxide, calcium jetoxide, and calcium dibropoxide, and carboxylic acid salts. In addition, non-Ca salt type phosphorus reactive oxygen acid compounds include H, PO4, &tKH2PO4, NH4H, PO
4゜(NH4)2 HP 04, (NH4)
In addition to phosphates such as s P 04, various phosphorus oxygen acid alkoxides such as phosphoric trimethoxide, phosphoric triethoxide, phosphoric acid tripropoxide, phosphorous trimethoxide, phosphorous triethoxide, phosphorous tripropoxide, trimethyl phosphate, meth Non-limiting examples include esters of various phosphorus oxygen acids such as ethyl phosphate, monoethyl phosphate, diethyl phosphate, triethyl phosphate, and ethyl pyrophosphate.

The non-phosphate type reactive Ca compound and the non-Ca salt type reactive oxygen acid compound of phosphorus are dissolved in water and/or a wood-philic organic solvent at a temperature of 50°C or less in a composition such that a predetermined Ca/P is obtained. This raw material solution is heated to a temperature of 70°C.
It is dropped into the production reaction tank 1a maintained at a temperature of .degree. C. or higher and a pH of 4 or higher (preferably 8 to 11) through a raw material supply pipe 7.7.

The solution for dissolving the Ca compound and the P compound or the solution to which the dissolution solution is dropped include methanol, ethanol, acetone, ether, etc. as hydrophilic organic solvents other than water. The liquid and the dripping liquid may be the same or different. Further, it is preferable that the Ca/P of the blended raw materials is 1.3 or more.

In the production reaction tank 1a, the heater 3 and the pH
The adjustment pipe 10 is configured to maintain the temperature and pH of the internal solution at the above-mentioned constant values, and HAP nuclei are formed by dropping the raw material solution. Then, the solution 2a containing the nuclei is passed through the connecting pipe 5 to the ripening tank! The grains are continuously fed to the aging tank 1b, and grain growth progresses around the core.

In this scouring reaction tank 1a, the pH and temperature will slightly fluctuate locally due to the introduction of the raw material solution, but since the capacity of the reaction tank is smaller than conventional ones, the state of the solution in the tank can be easily checked. Since it can be made homogeneous and fluctuations in pH and temperature can be easily kept constant, HAP nuclei can be formed in a stable production environment. Furthermore, since solutions 2a and 2b are configured to maintain almost the same temperature and pH, even if solution 2a containing HAP nuclei is introduced into solution 2b, the temperature and pH of solution 2b will change. is extremely small compared to conventional devices. Therefore, in the mature acid bath 1b, grain growth progresses under a substantially constant environment, and the variation in grain size is extremely small, and the shape of the HAP fine grains is also formed uniformly. In addition, the above-mentioned ripening, 1llllb is the production reaction tank 1a.
It is preferable to have a larger capacity, and by doing so, it becomes possible to utilize the large heat capacity of the solution and to suppress fluctuations in the temperature inside the tank as much as possible. Furthermore, if the production reaction tank 1a is configured to be immersed in the solution in the ripening tank 1b as shown in Fig. 1, temperature fluctuations in the production reaction tank 1a can be suppressed due to the heat capacity of the solution 2b in the ripening tank 1b. can.

FIG. 2 is a cross-sectional explanatory diagram showing another embodiment of the present invention,
The production reaction tank 1a is arranged above the ripening tank 1b, and through the downstream connection part 5A formed at the bottom of the production reaction tank 1a,
The structure is such that a solution 2a containing HAP nuclei flows down to a ripening tank. Further, a flow rate adjustment valve 8 is disposed at a midway position of the downstream connecting portion 5A, and is configured to adjust the amount of the solution 2a to be fed.

FIG. 3 is an explanatory diagram showing another embodiment of the present invention, in which the production reaction tank 1a, the aging tank 1b, and the production reaction tank 1a are
and a solution 4ii1c to which a solution whose temperature is maintained at a constant value is supplied via the solution supply pipe 11. In this example, an in-tank liquid level controller 12 is disposed in the production reaction tank 1a, and is configured to be able to adjust the feeding amount of the solution 2c.

Note that the solution tank 1c and the liquid level controller 12 can be provided in the embodiments shown in FIGS. 1 and 2, and are not limited to this embodiment.

[Effects of the Invention] Since the present invention is configured as described above, the manufactured H
The particle size distribution of the AP fine particles can be made within a narrow range, and the shape of the HAP fine particles can also be made uniform.

[Brief explanation of the drawing]

Fig. 1 is a cross-sectional explanatory diagram showing a typical embodiment of the present invention, Figs. 2 and 3 are cross-sectional explanatory diagrams showing other embodiments of the present invention, and Fig. 4 is a cross-sectional diagram showing a conventional device. It is an explanatory diagram. 1... Reservoir 3... Heater 6... Stirrer 8... Flow rate adjustment valve 11... Solution supply pipe 2... Solvent 5... Connecting pipe 7... Raw material liquid supply pipe 10...pH adjustment piping 12...liquid level controller

Claims (1)

[Claims] (1) A non-phosphate reactive Ca compound and a non-Ca salt type phosphorus are added to a storage tank of water and/or a hydrophilic organic solvent equipped with a heating mechanism and a pH adjustment mechanism to achieve a predetermined Ca/P. In an apparatus for producing hydroxyapatite fine particles, the storage tank is a production reaction tank, and the storage tank is a production reaction tank. and a ripening tank, the supply pipe is connected to the production reaction tank, and the production reaction tank and the ripening tank are connected by a connecting pipe.