JPH07187623A - Production of apatite fibrous body - Google Patents

Abstract

PURPOSE:To produce an apatite fibrous body having high purity of the apatite and satisfactory strength. CONSTITUTION:A spinning soln. contg. an ionic org. high molecular compd. forming a water-insoluble calcium salt, slightly water-soluble calcium phosphate and water is spun in a hardening soln. made of an aq. soln. contg. a water-soluble calcium salt to form a composite spun body consisting of a water-insoluble org. high molecular compd. and slightly water-soluble calcium phosphate. This spun body is compacted into a desired shape and fired to produce the objective apatite fibrous body.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing an apatite fiber body which is useful as a filling material for a bone defect or void, a reinforcing material or a hemostatic material, or as a filling material for a separation column of biological components.

[0002]

2. Description of the Related Art Conventionally, in the medical fields such as dentistry, orthopedics, and surgery, when a bone defect occurs, bone graft with autologous bone or allogeneic bone has been performed as a method for treating the bone defect. However, in recent years, such bone transplantation has been pointed out to its limits due to problems such as difficulty in securing a large amount of bones and causing mental distress to bone donors.

Under these circumstances, therefore, artificial bones and bone filling materials have been actively developed as a substitute for the conventionally used autogenous bones and allogenic bones. As materials for these artificial bones and bone fillers, metals and ceramics have been mainly studied, but among them, apatite, which is one of calcium phosphate-based ceramics, is
As a biocompatible material that has the property of directly binding to bone, it has been put to practical use.

Generally, apatite is M ₁₀ (Z
O ₄ ) ₆ X ₂ means a substance, and in the present specification, the apatite is M in the above general formula, calcium is Z, phosphorus is Z,
Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ (calcium hydroxyapatite) in which X is a hydroxyl group, and those in which some or all of the hydroxyl groups are replaced with atoms or groups such as fluorine, carbonate, chlorine, oxygen, That is, calcium fluoride (hydroxy) apatite, calcium carbonate (hydroxy) apatite, calcium chloride (hydroxy) apatite, oxycalcium (hydroxy)
Refers to apatite, etc. Further, in all of these compounds, the molar ratio of calcium to phosphorus (Ca / P molar ratio)
Is 1.67.

Various dosage forms such as granules, powders, blocks, and fibrous materials have been developed for the above-mentioned bone filling material using apatite. Therefore, after the treatment, there is a problem that the bone filler is extruded by body fluid, the surgical site is deformed, and the block-shaped one is difficult to take a complicated shape.

[0006] However, the fibrous materials are advantageous over these dosage forms in that the details of the void can be filled and the fibers are hardly entangled and moved from the surgical site after the filling. On the other hand, since apatite is a crystalline substance by nature, it is difficult to make it fibrous, and even if it is made fibrous, it is necessary for easy treatment and easy handling. There is a problem in that an apatite fiber body having a strong and tight particle structure cannot be obtained. It has also been desired that the purity of apatite be extremely high in order to promote bone formation and enhance adsorption capacity.

Therefore, in order to obtain an apatite fiber body which meets these conditions, various apatite fiber bodies and a method for producing the same have been disclosed as follows.

(1) Method for obtaining calcium phosphate fibers by melt spinning calcium phosphate at high temperature (Japanese Patent Publication No. 2-10)
244).

(2) Calcium phosphate fiber obtained by forming a composite fiber of calcium phosphate and calcium alginate by a wet method, and firing the composite fiber (JP-A-63-63).
-226360 and JP-A-63-145418).

(3) Calcium phosphate fiber obtained by forming a composite fiber of calcium phosphate and an organic polymer binder by a wet method and firing the composite fiber (JP-A-62-62).
No. 221358).

[0011]

However, the above-mentioned prior art has the following problems.

(1) In the method disclosed in Japanese Examined Patent Publication No. 2-10244, melt spinning is carried out at an extremely high temperature, so a large amount of OH groups essential for apatite disappear during melting. Further, in order to easily make apatite, which is not originally glassy, into fibers, it is necessary to add a binder-like substance, and it is difficult to obtain high-purity apatite.

(2) The methods proposed in JP-A-63-226360 and JP-A-63-145418 are the simplest methods for obtaining this type of composite fiber body by a wet method. Since the film formed on the surface of the fiber by alginic acid is strong, the reaction components do not sufficiently penetrate into the inside of the fiber, and thus a composite fiber body having a high calcium phosphate inorganic content cannot be obtained. Further, the reaction component ratio inside the fiber is different from the charged amount, and it is difficult to control the produced calcium phosphate to be apatite.

Further, when this composite fiber body is fired to form calcium phosphate fiber, the amount of calcium phosphate in the composite fiber is small for the above reason, so that only fiber having low strength can be obtained. Further, since the crystal seeds produced are not always apatite, and the calcium of the calcium alginate used as a raw material remains after firing and is difficult to remove, only calcium phosphate fibers with low apatite purity can be obtained.

(3) The method proposed in Japanese Patent Application Laid-Open No. 62-221358 uses apatite powder produced in advance to form a composite fiber body which is then fired to form calcium phosphate fiber. In this case, the bond between the apatite particles is weak, so that the strength of the obtained fiber is extremely low.

As described above, as a filling material for bone defects,
Compared with other materials, calcium phosphate-based compound fibers, which have the advantage that they can be filled in defect parts of various shapes and that there is little leakage after filling, especially apatite fiber bodies, strength and In terms of purity, no product has been obtained that can be sufficiently used. Further, due to this lack of strength and purity, the apatite fiber body has not been used for purposes other than biomaterials such as a packing material for a protein separation column.

The present invention, in order to overcome the above problems,
It is an object of the present invention to provide a method for producing an apatite fibrous body having high apatite purity and sufficient strength.

[0018]

Means for Solving the Problems As a result of intensive studies to solve the above-mentioned problems, the present inventor has utilized a technique of liquid phase spinning an ionic organic polymer compound to obtain a water-insoluble calcium salt. In the step of water-insolubilizing the ionic organic polymer compound that forms the compound, when it is combined with a water-insoluble calcium phosphate compound to form a spinning body, the concentration of calcium phosphate in the resulting composite spinning body increases, and It was found that when the spun body is fired, it becomes a high-purity apatite fiber body, and further that the relative density of the apatite in the apatite fiber body is high and the bond between particles is strong, and thus the present invention has been completed. .

That is, according to the present invention, a spinning dope containing an ionic organic polymer compound forming a water-insoluble calcium salt, a sparingly water-soluble calcium phosphate, and water is spun in a hardening solution composed of an aqueous solution containing a water-soluble calcium salt. By forming a composite spinning body of a water-insoluble organic polymer and a sparingly water-soluble calcium phosphate, the method for producing an apatite fiber body characterized by molding the obtained composite spinning body into a desired shape and firing. is there.

The present invention will be described in detail below. Regarding the method for producing an apatite fiber body of the present invention, first, a spinning stock solution,
The curing liquid will be described.

<1> Spinning stock solution The spinning stock solution used in the present invention contains three components: an ionic organic polymer compound forming a water-insoluble calcium salt, a sparingly water-soluble calcium phosphate, and water.

(1) Ionic Organic Polymer Compound The ionic organic polymer compound used in the spinning dope of the present invention is a compound which becomes insoluble in water when it reacts with calcium ions to form a calcium salt. Examples of the compounds include alginic acid, alkali salts of polysaccharides such as xanthan gum, polyacrylic acid, carboxydextran, and alkali salts of semi-synthetic or synthetic organic polymer compounds such as carboxymethyl cellulose.
Of these polymer compounds, alginic acid, polyacrylic acid, and alkali salts of carboxymethyl cellulose are preferably used. These compounds can be used alone or as a mixture of two or more kinds.

Further, the compounding amount is preferably 1 to 10% by weight based on the total amount of the spinning dope.

(2) Water-insoluble calcium phosphate The water-insoluble calcium phosphate used in the spinning dope is calcium monohydrogen phosphate (CaHPO ₄ ), tricalcium phosphate (Ca ₃ (PO ₄ ) ₂ ), tetracalcium phosphate. (Ca ₄ (PO ₄ ) ₂ O) and other orthophosphoric acid-based calcium salts, calcium phosphite (CaPHO ₃ ) and other phosphite-based calcium salts, and calcium pyrophosphate (Ca ₂
Examples thereof include calcium phosphate having a low solubility in water, such as condensed phosphoric acid-based calcium salts such as P ₂ O ₇ ) and calcium metaphosphate (Ca (PO ₃ ) ₂ ). In the present invention, these may be used alone or in combination of two or more.

Orthophosphoric acid-based calcium dihydrogen phosphate (Ca (H ₂ PO ₄ ) _{2 having} a solubility of 12 g / 100
g) and calcium phosphates which are soluble in water to some extent like most commercially available hypophosphorous acid and hypophosphoric acid calcium salts cannot be used in the present invention.

Further, in the present invention, the sparingly water-soluble calcium phosphate has a solubility in water of 0.02 at 20 ° C.
It is preferably g / 100 g or less and the intramolecular Ca / P molar ratio is less than 1.67.

When a water-insoluble calcium phosphate having a solubility in water of more than 0.02 g / 100 g at 20 ° C. is used, it becomes difficult to form a composite spun body for the following reasons, or even a spun body is obtained. Also, Ca / of apatite in the apatite fiber body obtained by firing this
In some cases, the P molar ratio cannot be 1.67.

It is difficult to form a composite spinning body because, when an apatite fiber body is obtained using water-soluble calcium phosphate, the ionic organic polymer in the spinning stock solution is adjusted while the spinning stock solution is being adjusted. This is because the compound reacts with calcium ions eluted from calcium phosphate to form a water-insoluble organic polymer, which cures the spinning dope before the spinning step is carried out, making it substantially impossible to spin into the curing solution.

The degree of curing of the spinning dope during preparation of the spinning dope depends on the solubility of the water-soluble calcium phosphate used, and for example, the solubility of the water-soluble calcium phosphate is relatively low, and the reaction with the ionic organic polymer compound is partially cured. In some cases, a spinning stock solution capable of spinning in a slow state can be prepared. In such a case, even if a spinning body is obtained, the amount of calcium phosphate in the spinning body is
It changes compared with the time of preparation, and therefore, it is difficult to accurately control the Ca / P molar ratio of the apatite fiber body even if this spun body is fired.

Further, Ca /, which is a sparingly water-soluble calcium phosphate,
When a P molar ratio of 1.67 or more is used, the Ca / P molar ratio of the finally obtained apatite fiber body is always 1.6.
7. The Ca / P molar ratio of pure apatite is 1.67 or more, which is not preferable because the purity of apatite is low.

That is, apatite is a water-insoluble organic compound when a composite spinning body of a water-insoluble organic polymer compound formed by the reaction of an ionic organic polymer compound with calcium ions in a hardening liquid and a sparingly water-soluble calcium phosphate is fired. Calcium oxide, which is the combustion ash of a polymer compound, reacts with water-insoluble calcium phosphate. If the calcium phosphate as a raw material and the ionic organic polymer compound react in the spinning dope, the resulting apatite fiber body will lack calcium, and if the Ca / P molar ratio of the slightly water-soluble calcium phosphate as a raw material is When it is 1.67 or more, the produced apatite fiber body has an excessive amount of calcium, and in both cases, an apatite fiber body having a low apatite purity is obtained.

As such a sparingly water-soluble calcium phosphate, among the above-mentioned calcium phosphates, in the orthophosphoric acid system, calcium monohydrogen phosphate (CaHPO ₄ , Ca / P) is used.
= 1.0, solubility 0.02 g / 100 g), tricalcium phosphate (Ca ₃ (PO ₄ ) ₂ , Ca / P = 1.5, solubility PPM / 100 g), etc. (CaPHO ₃ , Ca / P = 1.0, solubility 0.02 g / 100 g), etc., but in the condensed phosphoric acid system, calcium pyrophosphate (Ca ₂ P ₂ O ₇ , Ca / P = 1.0,
Solubility PPM / 100g), calcium metaphosphate (C
a (PO ₃ ) ₂ , Ca / P = 1.0, solubility PPM / 10
0g) and the like. Moreover, the above-mentioned orthophosphoric acid-based tetracalcium phosphate (Ca ₄ (PO ₄ ) ₂ O) is Ca /
The P molar ratio is as high as 2.0, which is not preferable.

By the way, it is known that calcium phosphates differ in chemical composition even if they are regarded as crystallographically isomorphic. For example, Ca _10-X (HPO ₄ ) _X (PO ₄ )
_6-X (OH) _2-X・ nH ₂ O (X = 0 to 1, n = 0 to 2)
That is what is indicated by, which is called non-stoichiometric apatite. The chemical composition of this non-stoichiometric apatite is represented by the Ca / P molar ratio, and takes a value from around 1.3 to less than 1.67. The solubility of such non-stoichiometric apatite is almost equal to that of tricalcium phosphate, and they can also be used as the sparingly water-soluble calcium phosphate of the present invention.

Furthermore, the greater the amount of the sparingly water-soluble calcium phosphate in the composite spine and the more evenly dispersed the sparingly water-soluble calcium phosphate, the more the calcium oxide and the sparingly water-soluble when the composite spine is fired. The reaction density of calcium phosphate increases, and as a result, a strong apatite fiber body is obtained.

Therefore, when the amount of the ionic organic polymer compound is constant, the amount of the water-insoluble organic polymer compound produced is also constant, assuming that the ion exchange reaction in the curing liquid is 100%. The amount of calcium oxide formed by combustion of the water-insoluble organic polymer compound is also constant, and calcium oxide, a sparingly water-soluble calcium phosphate (Ca / P molar ratio <1.67) and apatite (Ca / P molar ratio = 1. 6
It is considered that calcium oxide supplements the calcium deficiency of the sparingly water-soluble calcium phosphate in the reaction that causes 7), so that the Ca / P molar ratio of the sparingly water-soluble calcium phosphate is 1.
The closer to 67, the more can be put.

From this, it is more preferable that the slightly water-soluble calcium phosphate of the present invention has a Ca / P molar ratio close to 1.67. As such, tricalcium phosphate and Ca / P molar ratio of 1.67 are preferable. Non-stoichiometric apatite close to 67 can be mentioned.

The powder particle size of these sparingly water-soluble calcium phosphates is not particularly limited, but 100 for uniform dispersion.
μm or less is desirable. The blending amount of the sparingly water-soluble calcium phosphate cannot be limited because it depends on the type and amount of the ionic organic polymer compound used, but it is preferably 1 to 10% by weight with respect to the total spinning stock solution. is there.

With respect to this blending amount, according to the method for producing an apatite fiber body of the present invention, the higher the blending amount of the sparingly water-soluble calcium phosphate used is, the more preferable it is in order to increase the particle density of the apatite formed during firing. On the other hand, in order to control the Ca / P molar ratio of the produced apatite, it is necessary to adjust the type and blending amount of the sparingly water-soluble calcium phosphate according to the type and amount of the ionic organic polymer compound used. Further, in this case, the molecular weight distribution of the ionic organic polymer compound used and the reaction rate of the ionic organic polymer compound with calcium ions in the curing liquid must also be considered.

(3) Water and Other Optional Components The amount of water used in the spinning dope of the present invention is preferably 50 to 98% by weight based on the total amount.

The spinning dope used in the present invention contains, in addition to the ionic organic polymer compound, the sparingly water-soluble calcium phosphate and water, a modifying agent for changing the composition of the apatite produced, if necessary. Water admixture for adjusting the osmotic pressure between the ionic organic polymer compound fiber membrane and the curing liquid, p
An H regulator and the like can be added.

Examples of the modifier include calcium fluoride.
Cium (CaF₂), Calcium carbonate (CaCO₃),
Hydrochloric acid (HCl) and the like can be mentioned. These are the eyes
Depending on the purpose, blend one or more kinds into the spinning dope.
You can For example, these modifiers
Fluoro (F), carbonate (C
O ₃), Chlorine (Cl), etc. are introduced to fluorinate,
Carbonated and chlorinated calcium hydroxyapatite and
And when trying to obtain a mixture of these.
The blending amount depends on the degree of modification of the desired apatite.
However, it is almost 10 times the amount of water-insoluble calcium phosphate.
It is preferably less than 5% by weight, more preferably less than 5% by weight.
It is a large amount.

Next, the water admixture and the pH adjuster will be described in detail. The purpose of adjusting the osmotic pressure between the ionic organic polymer compound fiber film and the curing liquid by using a water admixture and / or a pH adjusting agent is to insolubilize the ionic organic polymer compound in the curing liquid. (Cation substitution reaction) is promoted to increase the particle density of the finally formed apatite.

That is, in order to increase the particle density of the produced apatite, the ionic organic polymer compound is insolubilized during the formation of the composite spinning body to form the composite spinning body. At this time, for example, sodium occurs. It is important to cause more cation substitution reaction such as cation substitution of calcium with calcium inside the composite spinning body.

Therefore, in order to promote such a cation substitution reaction, a water admixture and / or a pH adjusting agent is used to adjust the osmotic pressure of both the composite spinning body and the hardening liquid, and to control the liquidity. Then, the infiltration of calcium ions into the composite spinning body is facilitated, and the concentration of calcium ions in the composite spinning body is increased.

As a secondary effect of the water admixture, for example, when ethanol is used in the curing liquid, the specific gravity of the curing liquid can be lowered and the composite spinning body can be prevented from floating on the surface of the curing liquid. As a result, the effect of adjusting the osmotic pressure can be enhanced.

Examples of the water admixture having the above-mentioned function used in the spinning dope of the present invention include lower alcohols such as methanol and ethanol, lower polyhydric alcohols such as ethylene glycol and propylene glycol, and ethylene such as methyl cellosolve and ethyl cellosolve. Examples thereof include alkylene oxide lower polymers such as glycol monoalkyl ethers, diethylene glycol and dipropylene glycol.

The blending amount of the water admixture in the spinning dope depends on the kind and amount of the ionic organic polymer compound used, but it is generally in the range of 5 to 40% by weight based on the total amount of the spinning dope. When a water admixture is added to the spinning dope, a part of the water in the spinning dope may be replaced with the water admixture.

The pH adjusting agent used in the spinning dope of the present invention includes common alkaline agents such as sodium hydroxide and ammonium hydroxide, common acidic reagents such as hydrochloric acid and nitric acid, and methylamine, ethylamine and monoethanolamine. And the like, secondary amines such as dimethylamine, diethylamine and diethanolamine, tertiary amines such as trimethylamine, triethylamine and triethanolamine, and diamines such as ethylenediamine and trimethylenediamine.

The amount of the pH adjuster blended in the spinning dope is not limited because it varies depending on various factors such as the type and amount of the ionic organic polymer compound used and the amount of the water-miscible solvent. It is used in the range of approximately 1 to 20% by weight based on the total amount of the spinning dope. Also in this case, as in the case of the water admixture, part of the water in the spinning dope may be replaced with a pH adjuster.

<2> Curing Liquid The curing liquid used in the present invention comprises an aqueous solution containing at least a water-soluble calcium salt.

Examples of the water-soluble calcium salt used in this hardening liquid include common water-soluble calcium salts such as calcium nitrate, calcium acetate, calcium lactate and calcium chloride. The amount of the water-soluble calcium salt to be added to the hardening liquid varies depending on the concentration of the ionic organic polymer compound in the spinning dope, but is used in the range of 4 to 30% by weight based on the total amount of the hardening liquid.

The content of water in the curing liquid is in the range of 65 to 96% by weight based on the total amount of the curing liquid. The curing liquid also contains the above-mentioned water-soluble calcium salt and a component other than water,
As with the spinning dope, a water admixture or a pH adjuster can be used.

The purpose of using these water admixtures and pH adjusters, their specific examples, and their compounding amounts are exactly the same as in the case of using them as the spinning dope. Next, the method for producing the apatite fiber body of the present invention will be described in detail.

<3> Method for producing apatite fibrous body of the present invention The apatite fibrous body of the present invention comprises the steps of preparing the above spinning dope and the hardening liquid, spinning the spinning dope in the hardening liquid, and the water-insoluble organic polymer. It is manufactured by obtaining a spinning step of forming a composite spinning body of a compound and a sparingly water-soluble calcium phosphate, a molding step of shaping the obtained composite spinning body into a desired shape, and a firing step.

(1) Steps for preparing a spinning dope and a curing liquid The spinning dope and the curing liquid are prepared by mixing the above-mentioned components. The point in this step is to increase the particle density of the generated apatite, in order to increase the concentration of the ionic organic polymer compound and the sparingly water-soluble calcium phosphate in the spinning dope as high as possible within the preferred range, and also the ion The osmotic pressure of both the composite spinning body (spinning stock solution) and the hardening solution is adjusted so that the insolubilization reaction of the organic polymer compound is promoted.

(2) Spinning Step The spinning method used in the spinning step of the present invention may be any method used in ordinary liquid phase spinning, for example, the following method can be used for spinning. A spinning stock solution containing an ionic organic polymer compound forming a water-insoluble calcium salt prepared in (1), a sparingly water-soluble calcium phosphate and water is put into a cylinder equipped with a nozzle, and the spinning stock solution in the cylinder is provided with a piston. Alternatively, pressure is applied with a compressed gas or the like, and the mixture is extruded from a nozzle at a constant speed into a hardening liquid also containing the water-soluble calcium salt prepared in (1) and water.

The spinning dope extruded in this way is
In this curing liquid, the ionic organic polymer compound reacts with calcium ions to cure and insolubilize to form a composite spinning body of an insoluble organic polymer compound and a sparingly water-soluble calcium phosphate.

The diameter of the nozzle used at this time is not particularly limited, but a range of 0.1 mm to 1.0 mm is suitable. The temperature of the spinning dope and the curing liquid during spinning is not particularly limited because the curing reaction of the ionic organic polymer compound is not so much affected by the temperature, but the temperature may be related to the adjustment of the osmotic pressure, and the temperature is generally 5 ° C to 80 ° C. The range of ° C is preferred. The curing time varies depending on the fiber diameter of the spun body, but is generally 30 minutes or more at 0.5 mm with a fiber diameter of 1.0 mm.
It is preferable to age for 10 minutes or more at m or less.

(3) Molding Step Next, the composite spun body spun in the above-mentioned spinning step is taken out from the curable liquid and molded into a desired shape. As a shape for molding the composite spun body, a single fiber body or an aggregate of two or more fibers is preferably exemplified.

When the composite spun body is molded as a single fiber body, for example, the tip of the composite spun body is pulled out from the curable liquid and successively passed through a drying device or the like adjusted to 70 ° C to 120 ° C. You can wind it up.

When the composite spun body is made up of two or more aggregates, sheet-like, cotton-like and block-like ones are particularly preferable. In order to obtain a sheet-shaped product, for example, the composite spun body is cut into short fibers in the spinning step, and the short fibers are strained from the curable liquid in the same manner as straining paper and pressed at room temperature to 110 ° C. It may be dried at a temperature of about ℃.

The cotton-like material can be obtained, for example, by cutting the composite spinning body into short fibers in the spinning step, and lyophilizing the resulting short fiber-dispersed hardening liquid as it is. Further, in order to obtain a block-shaped product, for example, a product formed as a single fiber body as described above may be cut into an appropriate length, and several pieces may be bundled and pressed at room temperature.

Here, it is necessary to take care so as not to cause a reaction that causes a change in the Ca / P molar ratio of the composite spinning body after the spinning process and before the firing process, that is, in this molding process. . This is because the Ca / P molar ratio of the produced apatite fiber body is strictly controlled at the spinning stage.

(4) Firing Step In the manufacturing method of the present invention, the firing step is an important step of producing apatite constituting the final target apatite fibrous body. That is, the composite spun body obtained after obtaining the spinning step is composed of a water-insoluble organic polymer compound which is insolubilized in water by reacting the ionic organic polymer compound with calcium ions in the curing liquid and a sparingly water-soluble calcium phosphate. By firing the spinning body, first, the organic matter is burned and gasified and scattered to change the calcium content in the water-insoluble organic polymer compound into calcium oxide, and then the calcium oxide and the slightly water-soluble calcium phosphate react with each other. To produce apatite. Therefore, it is desirable that the firing step be performed under conditions that allow these reactions to proceed smoothly.

The composite spinning bodies molded into various shapes in the above step (3) are put in a firing furnace, and an optional temperature-raising firing schedule is selected according to various shapes, and finally a temperature of 1000 ° C.
Bake at 1250 ° C for any time.

It should be noted that in the firing process,
Before the firing treatment at the final temperature of 1000 ° C. to 1250 ° C. at which the solid-phase reaction of calcium oxide and water-insoluble calcium phosphate is carried out, the organic matter in the composite spinning body is completely burned. For that purpose, it is preferable to know in advance how many times the organic matter is completely burned, and to process the composite spinning body at that temperature for a sufficient time. The temperature and the holding time of the step of burning the organic matter greatly vary depending on the type and amount of the ionic organic polymer compound used in the spinning dope, and the shape of the composite spinning body, so it is preferable to carry out under each suitable condition. .

For example, in the case of a single fiber body, the temperature rising rate is 1 to 50 ° C./min, the temperature is maintained at 300 to 400 ° C. for about 1 to 6 hours, and further at 600 to 700 ° C. for 3 to 12 hours. Hold for about an hour, final temperature 1000 ℃ ~ 1250
After being kept at 6 ° C for 48 hours, it is cooled to room temperature and taken out from the firing furnace.

When firing the block-shaped composite spinning body, depending on the size, 300 ° C. and 600 ° C. of the former stage are used.
Adjusting the temperature holding time near ℃ to be sufficient,
After holding the temperature around 600 ° C to 900 ° C in a vacuum once, returning it to room temperature, and then performing a process such as performing a temperature holding process similar to the process in a vacuum, the final temperature It is preferable to raise the temperature up to and complete firing.

[0069]

According to the method for producing an apatite fiber body of the present invention, first, a spinning stock solution containing an ionic organic polymer compound that forms a water-insoluble calcium salt, a sparingly water-soluble calcium phosphate and water is added to a water-soluble calcium salt. Is spun in a curing liquid containing. In this step, the ionic organic polymer compound in the spinning dope contacts with the calcium ions in the curing liquid to react and insolubilize and harden, but at the time of this curing, the water-insoluble organic polymer compound incorporates the slightly water-soluble calcium phosphate compound. Then, a composite spun body in which both are uniformly mixed is formed.

When the composite spinning body thus obtained is molded into a desired shape and baked, the water-insoluble organic polymer compound in which the ionic organic polymer compound is insolubilized in the curing liquid is completely burned, and then the Calcium oxide, which is the combustion ash content, and the sparingly water-soluble calcium phosphate undergo a solid-phase reaction to uniformly generate apatite, resulting in a high-strength apatite fiber body having extremely strong interparticle bonds.

Further, according to the production method of the present invention, the Ca / P molar ratio is sufficiently controlled at the stage of forming the composite spun body in the spinning step, and it is obtained by molding and firing this composite spun body. The apatite fiber body has a very high apatite purity.

[0072]

EXAMPLES Examples of the present invention will be described below. First, an example of producing a spinning dope and a curing liquid used in the method for producing an apatite fiber body of the present invention will be described.

[0073]

[Manufacturing Examples 1 to 6] Spinning stock solution The components shown in Table 1 were mixed and stirred well to prepare a spinning stock solution in which a solid solution was uniformly mixed and dispersed.

[0074]

[Table 1]

[0075]

[Production Examples 7 to 10] Curing liquid The components shown in Table 2 were mixed to prepare a curing liquid.

[0076]

[Table 2]

Next, examples of the present invention using the spinning dope and the curing liquid obtained in each of the above production examples will be described.

[0078]

Example 1 The spinning solution obtained in the above Production Example 1 was put into a 200 ml capacity cylinder equipped with a nozzle (diameter 0.2 mm), and the gas pressure inside the cylinder was adjusted to 600 mm.
A spinning body was extruded at a spinning speed of / min into the curing liquid (temperature; room temperature) obtained in Production Example 7. The tip of this spinning body was taken out from the hardening liquid and passed through running water for 10 more minutes.
After passing through a tunnel furnace at 0 ° C., it was wound by a winder.

Then, the wound bundle was placed in an electric furnace as it was, heated to 1250 ° C. at a temperature rising rate of 10 ° C./min and kept at that temperature for 3 hours, and then cooled to room temperature in the furnace. A long fibrous single fiber body was obtained. The long fibrous single fiber body was an apatite fiber body having a very smooth surface.

[0080]

Example 2 The spinning solution obtained in the above Production Example 1 was put into a 200 ml capacity cylinder equipped with a nozzle (diameter 0.2 mm), and the gas pressure inside the cylinder was adjusted to 1200 m.
At a spinning speed of m / min, the filament was extruded while moving the nozzle into the hardening liquid (temperature; room temperature) obtained in Production Example 7 which was flowing by stirring to obtain a short fiber spun body. The spun body was taken out from the curable liquid while filtering using a mesh, and two sheets were stacked and dehydrated by pressing, and naturally dried at room temperature to obtain a sheet-like spun body.

Then, this sheet-shaped spun body was put in an electric furnace and heated to 300 ° C. at a heating rate of 10 ° C./min in the atmosphere and kept at that temperature for 1 hour, followed by a heating rate of 10 ° C./min.
The temperature is raised to 600 ° C. in min and held at that temperature for 6 hours, and finally, the temperature is raised to 1250 ° C. at a heating rate of 10 ° C./min and the temperature is held for 3 hours to carry out stepwise firing.
This was furnace-cooled to room temperature to obtain a sheet-shaped fibrous body. This sheet-shaped fiber body was a hard apatite fiber body in which short fibers were entangled to form a sheet.

[0082]

Example 3 The spinning dope obtained in the above Production Example 1 was put into a 200 ml capacity cylinder equipped with a nozzle (diameter 0.2 mm) and the gas pressure inside the cylinder was adjusted to 1200 m.
At a spinning speed of m / min, the filament was extruded while moving the nozzle into the hardening liquid (temperature; room temperature) obtained in Production Example 7 which was flowing by stirring to obtain a short fiber spun body. The spun body was separated by filtration, dispersed again in purified water, and then freeze-dried.

Then, the obtained composite spun body was put in an electric furnace and heated to 1250 ° C. at a heating rate of 10 ° C./min in the atmosphere and kept at that temperature for 3 hours, and then cooled to room temperature in the furnace. To obtain a cotton-like monofilament. This cotton-like fibrous body was a cotton-like apatite fibrous body in which short fibers were gently entangled.

[0084]

Example 4 The spinning solution obtained in the above Production Example 2 was put into a 200 ml capacity cylinder equipped with a nozzle (diameter 0.5 mm), and the gas pressure inside the cylinder was adjusted to 600 mm.
A spinning body was extruded into the curing liquid (temperature; room temperature) obtained in Production Example 10 at a spinning speed of / min. The tip of this spinning body was taken out from the curable liquid, passed through running water, further passed through a tunnel furnace at 100 ° C., and then wound by a winder.

Then, the wound bundle is put into an electric furnace as it is, heated to 700 ° C. at a temperature rising rate of 5 ° C./min and kept at that temperature for 3 hours, and subsequently heated to 5 ° C./mi.
The temperature was raised to 1250 ° C. with n, and the temperature was maintained for 3 hours, followed by stepwise firing. The long fibrous body was an apatite fibrous body having a dense surface and a smooth surface.

[0086]

Example 5 The spinning solution obtained in the above Production Example 3 was put into a 200 ml capacity cylinder equipped with a nozzle (diameter 0.5 mm) and the gas pressure inside the cylinder was adjusted to 600 mm.
At a spinning speed of / min, the composition was extruded into the curable liquid (temperature 40 ° C.) obtained in Production Example 8 to prepare a spun body. The tip of this spinning body was taken out from the hardening liquid and passed through running water for 10 more minutes.
After passing through a tunnel furnace at 0 ° C., it was wound by a winder.

Then, the wound bundle is put in an electric furnace as it is, heated to 700 ° C. at a temperature rising rate of 5 ° C./min and kept at that temperature for 3 hours, and subsequently heated to 5 ° C./mi.
The temperature was raised to 1250 ° C. with n, and the temperature was maintained for 3 hours, followed by stepwise firing. This long fibrous fiber body was an apatite fiber body having a slightly uneven surface.

[0088]

Example 6 The spinning solution obtained in the above Production Example 4 was put into a 200 ml capacity cylinder equipped with a nozzle (diameter 0.5 mm) and the gas pressure inside the cylinder was adjusted to 600 mm.
At a spinning speed of / min, the composition was extruded into the curable liquid (temperature 40 ° C.) obtained in Production Example 8 to prepare a spun body. The tip of this spinning body was taken out from the hardening liquid and passed through running water for 10 more minutes.
After passing through a tunnel furnace at 0 ° C., it was wound by a winder.

Then, the wound bundle is put into an electric furnace as it is, heated to 700 ° C. at a temperature rising rate of 5 ° C./min and kept at that temperature for 3 hours, and subsequently heated to 5 ° C./mi.
The temperature was raised to 1250 ° C. with n, and the temperature was maintained for 3 hours, followed by stepwise firing. The long fibrous body was made of apatite containing fluorine and had an extremely smooth surface.

[0090]

Example 7 The spinning dope obtained in the above Production Example 5 was put into a 200 ml capacity cylinder equipped with a nozzle (diameter 0.5 mm) and the gas pressure inside the cylinder was adjusted to 600 mm.
A spinning body was extruded into the curing liquid (temperature; room temperature) obtained in Production Example 10 at a spinning speed of / min. The tip of this spinning body was taken out from the curable liquid, passed through running water, further passed through a tunnel furnace at 100 ° C., and then wound by a winder.

Then, the wound bundle is placed in an electric furnace as it is, heated to 700 ° C. at a temperature rising rate of 5 ° C./min and kept at that temperature for 3 hours, and subsequently heated to 5 ° C./min.
The temperature was raised to 1250 ° C., and the temperature was maintained for 3 hours, followed by stepwise firing, followed by furnace cooling to room temperature to obtain long fiber single fibers. This long fibrous fiber body was made of apatite containing a slight amount of chlorine, and was a smooth apatite fiber body having a slightly uneven surface.

[0092]

Example 8 The spinning solution obtained in the above Production Example 6 was put into a 200 ml capacity cylinder equipped with a nozzle (diameter 0.7 mm), and the gas pressure inside the cylinder was adjusted to 600 mm.
At a spinning speed of / min, the composition was extruded into the curable liquid (temperature; room temperature) obtained in Production Example 9 to obtain a spun body. The tip of this spinning body was taken out from the hardening liquid and passed through running water for 10 more minutes.
After passing through a tunnel furnace at 0 ° C., it was wound by a winder.

Then, the wound bundle is placed in an electric furnace as it is, heated to 900 ° C. at a temperature rising rate of 10 ° C./min under vacuum, kept at that temperature for 3 hours, cooled to room temperature, and again in the atmosphere. Then, the temperature was raised to 1250 ° C. at a temperature rising rate of 10 ° C./min, and the temperature was maintained for 3 hours, followed by firing by a method in which the firing atmosphere was changed, and this was furnace-cooled to room temperature to obtain a long fibrous single fiber body. . The long fibrous body was an apatite fibrous body having a smooth surface although the fiber diameter was considerably large.

[0094]

Example 9 The spinning solution obtained in the above Production Example 6 was put into a 200 ml capacity cylinder equipped with a nozzle (diameter 0.7 mm) and the gas pressure inside the cylinder was adjusted to 600 mm.
At a spinning speed of / min, the composition was extruded into the curable liquid (temperature; room temperature) obtained in Production Example 9 to obtain a spun body. The tip of this spinning body was taken out from the hardening liquid and passed through running water for 10 more minutes.
After passing through a tunnel furnace at 0 ° C., it was wound by a winder. The obtained long fibrous composite fiber body was cut into pieces of 10 cm each, and about 100 pieces of the cut spinning bodies were collected, set in a press die and vacuum-compressed to obtain a block-shaped spinning body.

Then, the block-shaped spinning body was put in an electric furnace and heated to 300 ° C. at a heating rate of 10 ° C./min under vacuum and kept at that temperature for 3 hours, followed by a heating rate of 1 ° C./min.
After raising the temperature to 700 ° C. in min and holding it at that temperature for 3 hours, the temperature is lowered to room temperature by cooling the furnace, and then the temperature rising rate is 1 in the atmosphere.
The temperature was raised to 1250 ° C. at 0 ° C./min, the temperature was maintained for 3 hours, and this was furnace-cooled to room temperature to obtain a block-shaped fibrous body.

[0096]

COMPARATIVE EXAMPLE 1 Sodium pyrophosphate (1.6 g) and sodium alginate (2.5 g) were added to purified water (45.9 g), and they were thoroughly stirred and completely dissolved to prepare a spinning dope. Separately, 8 g of calcium acetate and 2 g of calcium chloride were dissolved in 300 g of purified water, and the pH was adjusted to 7 with acetic acid to prepare a hardening liquid.

20 g of the spinning stock solution obtained above was extruded into the above-mentioned hardening solution from a spinning machine having a nozzle diameter of 0.2 mm and spun to give a spun body. The tip of this spinning body was taken out from the curable liquid, passed through running water, and then wound by a winder.

Then, the wound bundle is put into an electric furnace as it is, heated to 700 ° C. at a temperature rising rate of 5 ° C./min and kept at that temperature for 3 hours, and subsequently heated to 10 ° C./m.
The temperature was raised to 1250 ° C. in, the temperature was maintained for 3 hours, and the material was calcined stepwise, and this was cooled in a furnace to obtain long fiber-like short fiber bodies. This long fibrous fibrous body was an apatite fibrous body composed of apatite containing tricalcium phosphate as a subphase and having cuticle-like irregularities on the surface.

<Evaluation of Apatite Fibers Obtained by the Production Method of the Present Invention> Regarding the apatite fibers obtained in each of the above Examples and Comparative Examples, the single fiber diameter, shape, apatite crystal type, and apatite purity ( AP purity), Ca / P molar ratio in apatite, relative density, surface smoothness, and strength were measured and evaluated by the following methods.

<Single Fiber Diameter> The fiber cross-sectional diameter was measured by observation with an electron microscope (SEM).

<Shape> The macroscopic shape of the obtained fibrous body is shown.

<Crystal Form> A single phase was identified by X-ray diffraction.

<Mo / P molar ratio> Ca is an atomic absorption method, P
Was quantified using the ion chromatography method to calculate the Ca / P molar ratio. The theoretical values are 1.67 for apatite, 1.5 for tricalcium phosphate, and 1.0 for calcium pyrophosphate.

<AP Purity> C in the sample measured above
It was determined by the following calculation using the amount of a. The theoretical amount of Ca (the amount of Ca when the sample is 100% apatite) is divided by the amount of Ca in the sample and multiplied by 100 (unit is%).

<Relative Density> The relative density (unit:%) was obtained by dividing the density measured by the pycnometer method (measured density) by the theoretical density and multiplying by 100. The higher this value, the denser the apatite particles in the fibrous body.

<Smoothness> Smoothness means that the surface of the fiber body is SEM.
Was observed at 10,000 times and evaluated according to the following criteria.

⊚: Grain boundary is unclear ∘: Grain boundary is clear ∆: Grain boundary has gaps ×: Grain can be clearly observed

<Strength> The state when the fibrous body was crushed with a fingertip was evaluated according to the following criteria to evaluate the strength.

⊚: Long fiber shape remained ◯: Short fiber shape was divided Δ: Slightly powdery ×: Fairly powdery. The above results are shown in Table 3.

[0110]

[Table 3]

As is clear from these results, the apatite fiber body produced by the method of the present invention has a higher apatite purity, a single crystal structure, and a relative density as compared with the apatite fiber body of the comparative example. Is high, the connectivity between particles is good, the strength is high, and the smoothness of the surface of the fibrous body is excellent.

[0112]

EFFECTS OF THE INVENTION According to the method for producing an apatite fiber body of the present invention, an apatite fiber body having a high degree of apatite purity and good connectivity between apatite particles can be obtained, and thus an apatite fiber body having sufficient strength can be obtained.

When such an apatite fibrous body is used as a bone filler or the like, not only the operability during surgery can be improved, but also a high effect of promoting or reinforcing bone formation can be expected.

Furthermore, when the apatite fibrous body is used as a packing material for a separation column, it can be a packing material that is easy to handle and has a high separation ability.

Claims (5)

[Claims] 1. A spinning stock solution containing an ionic organic polymer compound forming a water-insoluble calcium salt, a sparingly water-soluble calcium phosphate, and water is spun in a hardening solution composed of an aqueous solution containing a water-soluble calcium salt, and water is added. A method for producing an apatite fiber body, which comprises forming a composite spinning body of an insoluble organic polymer compound and a sparingly water-soluble calcium phosphate, and shaping the obtained composite spinning body into a desired shape and firing. 2. The water-insoluble calcium phosphate has a solubility in water at 20 ° C. of 0.02 g / 100 g or less, and an intramolecular Ca / P molar ratio of less than 1.67. Item 2. A method for producing an apatite fiber body according to Item 1. 3. The composite spinning body is molded as a single fiber body in the molding step.
The method for producing an apatite fiber body according to. 4. The method for producing an apatite fiber body according to claim 1, wherein the composite spinning body is formed as an aggregate of fibers in the forming step. 5. The method for producing an apatite fiber body according to claim 4, wherein the aggregate of fibers has a sheet shape, a cotton shape, or a block shape.