JPH022974B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to an apatite flocculent body which has many uses such as medical use and use in microorganism mass culture ponds.

Conventional technology As is well known, apatite is M ₁₀ (ZO ₄ ) ₆ X ₂ (where M represents Ca, Ba, Sr, Pb, Cd, etc., and Z
represents P, As, V, etc., and X represents F, Cl, OH, etc.), and a typical example is hydroxyapatite Ca ₁₀ (PO ₄ ) ₆
(OH) ₂ , fluoroapatite Ca ₁₀ (PO ₄ ) ₆ F ₂ , etc. Hydroxyapatite is well known as a major inorganic component of teeth and bones, and the synthesized sintered body of hydroxyapatite shows excellent affinity for tooth and bone tissues and is directly attached to bone tissues and gums. Because it is chemically bonded, it is attracting attention as a so-called artificial implant material for new artificial teeth, artificial bones, materials, etc. Artificial tooth roots made of apatite sintered bodies and artificial bones made of apatite porous bodies have reached the stage of practical use.

However, since the apatite sintered body is a brittle material that is strong in compression but weak in tension, it is weak against impact and has the disadvantage that the tensile strength is greatly reduced by minute cracks that occur on the surface of the sintered body. It was hot. For this reason, the range of application of apatite sintered bodies to living organisms is very narrow, and the range of application of apatite sintered bodies to living bodies is limited to those where excessive tensile stress is not applied to them, for example, as artificial tooth roots for molars.

Problems to be Solved by the Invention In order to eliminate the drawbacks of the above-mentioned apatite sintered bodies, an inorganic fiber in which apatite is formed into a fibrous form and can be used as an implant material for bone defects or voids was disclosed in Japanese Patent Application Laid-open No. It is disclosed in No. 57-117621 and Japanese Unexamined Patent Publication No. 58-54023. However, the apatite fiber disclosed in the above publication is manufactured by a so-called melt spinning method, in which apatite is melted at high temperature and spun. As stated in the above publication, in this melt spinning method, apatite is melted at a high temperature of 1500°, so the hydroxyl groups of apatite disappear, resulting in a lack of affinity and compatibility with living organisms. Unlike hydroxyapatite, it could not be obtained in sufficient quantity.

As described above, when making hydroxyapatite into a fiber, in order to prevent the hydroxyl groups from disappearing, the above-mentioned melt spinning method cannot be adopted, and other methods such as melt spinning must be considered. However, a good binder, spinning method, and firing method for melt spinning have not been developed, and it has been impossible to make hydroxyapatite into a fiber while retaining its hydroxyl groups.

As a result of intensive studies to solve the drawbacks of conventional apatite fibers, the present inventors have found that hydroxyl groups can be removed by binding fine hydroxyapatite particles using a special binder and spinning them using a melt-spinning method. The inventors have discovered that a retained apatite flocculent can be easily provided, and have arrived at the present invention.

OBJECT OF THE INVENTION The present invention relates to the improvement of such apatite fibrous bodies, and an object of the present invention is to provide an apatite flocculent body consisting essentially of hydroxyapatite and having good biocompatibility. It is.

Means for Solving the Problems In the present invention, the term "apatite flocculent" refers to a state in which short apatite fibers are intertwined with each other.

The short fibers constituting the apatite floc in the present invention have an average fiber diameter of 1 to 30 μm, and the fiber length may be arbitrary within the range of 2 to 1000 mm.

The apatite flocculent of the present invention is produced by a solution spinning method in which fine hydroxyapatite particles are caked with a special binder and fired after spinning, and it retains hydroxyl groups, so its affinity does not disappear. Apatite flocs are obtained without the need for post-treatment.

More specifically, the flocculent material of the present invention can be produced by continuously spinning a viscous dispersion obtained by dispersing fine hydroxyapatite particles in an aqueous binder solution through a plurality of spinning holes installed in a spinning device. A predetermined gas is discharged at high speed from a gas discharge hole installed adjacent to the spinning hole, and the yarn from the spinning hole is drawn to form a fine fiber flow and heated to remove moisture. The fiber stream from which the apatite has been removed can be blown onto a collection device, such as a net-type collection belt, to obtain an apatite floc.

The hydroxyapatite fine particles used are preferably in the form of ultrafine particles, and have an average particle size of 50 Å or more.
Particularly preferred is one having a diameter of 1 μm. Although there is no particular restriction on the shape of the fine particles, rod-like shapes are preferred.
Such hydroxyapatite can be produced, for example, by gradually dropping an aqueous phosphoric acid solution into an alkaline solution (PH: 7 to 11) containing calcium ions.

The binder used is preferably one that satisfies at least two conditions: being harmless to living organisms and being water-soluble. As such a binder, in addition to polymer compounds such as polyvinyl alcohol, carboxymethyl cellulose, hydroxypropyl cellulose, and collagen, polymer polysaccharides such as pullulan, chitin, and dextran are preferred, with pullulan being particularly preferred. Pullulan is a linear glucan in which malitotriose is repeatedly linked through α-1,6-glycosidic bonds. When these polymer compounds are used as binders, their average molecular weight is preferably 20,000 to 2,000,000.
Particularly preferred are those with a value of 50,000 to 1,000,000.

In the present invention, the structure of an aqueous suspension consisting of hydroxyapatite and a binder includes water: 10 to 90% by weight,
Preferably 40-70% by weight, more preferably 50-65%
% by weight, hydroxyapatite: 5 to 70% by weight,
Preferably 15-50% by weight, more preferably 30-45%
Binder: 5-40% by weight, preferably 10-30% by weight, more preferably 20-25% by weight
It is. If the content of hydroxyapatite is less than 5% by weight, sufficient strength of the flocculent body cannot be obtained, and if it is more than 70% by weight, the viscosity increases.
Undesirable. In order to improve the dispersion of hydroxyapatite in the raw material liquid, for example, organic carboxylic acid is added, and glycerin, sorbitol, marquette, etc.
Plasticizers or softeners such as polyhydric alcohols such as ethylene glycol and propylene glycol can also be added. Furthermore, inorganic compounds other than apatite, such as calcium phosphate, can be added as dispersoids in an amount of less than 5% to improve the physical properties of the flocculent.

According to X-ray diffraction and infrared absorption analysis, hydroxyapatite has a structure of Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ when unfired and when fired at 1100°C or below, If the temperature is higher than this, for example 1300℃ or higher, the hydroxyl group will be lost and α-Ca ₃
(PO ₄ ) ₂ was observed.

Next, an outline of an example of the method for producing the apatite flocculent of the present invention will be explained with reference to FIG. 1.

First, hydroxyapatite, a binder, water, and if necessary, a dispersant, a plasticizer, a softener, etc. are charged into a raw material tank 2 through a raw material supply pipe 1 to prepare a viscous spinning solution. The raw material spinning solution is preferably about 20 to 70
Adjusted in °C. This viscous spinning solution is pushed out from the spinning nozzle 5 through a pipe line 15 by a gear popper 4 driven by a motor 3, and at the same time, the gas is raised to a high level by a blower 6 from an air nozzle 7 installed around the spinning nozzle. Protrude with speed. The spinning nozzle may, for example, consist of a plurality of dies arranged linearly in the width direction. A fiber stream 8 made of drawn fine fibers is formed by jetting gas, for example air, at a gas velocity of about 5 to 1000 m/sec and a temperature of about 20 to 60 DEG C. from around the nozzle. The fiber diameter and fiber length are determined by the pressure of the ejected gas.
For example, it can be arbitrarily adjusted to fall within the range of about 1 to 30 μm and 2 to 1000 mm.

Next, the fine fiber stream 8 is heated by a heating device provided below the spinning nozzle, such as an infrared heater 9, and the moisture in the fibers is evaporated to a water content of 10% by weight or less, preferably about 7% by weight or less. Remove and solidify. If water is removed excessively, a flocculent body of fine fibers cannot be obtained. In this case, the heating temperature for the fiber stream is selected depending on the amount of extrusion of the spinning solution, the temperature and amount balance of the ejected gas, etc., but usually the heater temperature is about 200-500℃ (the temperature of the fiber stream is about 80-150℃). ℃) range. If the heating temperature is set higher than necessary, the binder will decompose during the heating process, which is not preferable.

The fine fiber stream 10 that has been drawn, cut appropriately, and from which moisture has been removed as described above is blown onto a suitable collection device 11, such as a net-type collection container or a net-type collection belt, and is deposited and collected. Ru.

The flocculent body made of fine fibers bound by a binder has approximately 500 to
The apatite floc of the present invention can be obtained by firing at a temperature of 1250°C, preferably about 600 to 1200°C, more preferably 650 to 1100°C to eliminate the binder. When the firing temperature is 1200°C or less, the loss of hydroxyl groups is extremely small, and although it depends to some extent on the firing time, the loss of hydroxyl groups can be almost ignored. Therefore 1200 if necessary
It is possible to generate Ca ₃ (PO ₄ ) ₂ in an amount of less than 5% by weight in hydroxyapatite by raising the firing temperature higher than ℃, thereby improving the physical properties such as strength of the hydroxyapatite flocculent. Therefore, it is also possible to improve the physical properties as an implant material, for example.

The flocculent material thus obtained can be further processed depending on the purpose. For example, it can be improved to be more suitable by coating or impregnating it with collagen, and it can also be used as a mass culture medium by combining it with a culturing material such as pullulan.

Effects of the Invention The apatite flocculent body of the present invention substantially consists of hydroxyapatite, which is originally a major component of bone, and therefore has extremely good biocompatibility. In addition, since it is flocculent, it is extremely easy to process and handle when used for treatment. Furthermore, the culture amplification effect of flocculent apatite can be utilized to apply it to a microorganism mass culture pond.

EXAMPLES Hereinafter, the present invention will be explained in detail with reference to Examples, but the present invention is not limited thereto.

Examples Example 1 11% by weight of pullulan powder with an average molecular weight of 200,000, 17% by weight of hydroxyapatite powder (particle size 50-800 Å)
and 72% by weight of water were kneaded to uniformly disperse hydroxyapatite in the pullulan aqueous solution, and deaeration was performed. This solution was supplied at room temperature (25°C) to a device as shown in Figure 1, which has a die in which spinning nozzles with a diameter of 0.3 mm were arranged in a straight line in the width direction, and the pressure was 1.4 kg/1.
cm ² and 250 from the air gap
The fiber stream was formed by ejecting air at m/sec.
This fiber stream is heated from both sides of the fiber stream with a far-infrared heater (wavelength 2 to 50 μm) installed under the nozzle at a heater temperature of 400°C, and is blown onto a net-type collection belt to evaporate and remove moisture. A bonded hydroxyapatite flocculent was obtained. The resulting flocculent material was heated at a heating rate of 50°C/hour until the temperature reached 1100°C.
When baked at ℃ for 2 hours, pullulan disappeared,
A hydroxyapatite flocculent body having an average fiber diameter of 5 μm and an average fiber length of 50 mm was obtained. The resulting flocculent was examined by X-ray diffraction and IR analysis, and it was confirmed that hydroxyl groups were present in substantially the same amount as the raw material.

Comparative Example 1 Pullulan powder with an average molecular weight of 200,000 was dissolved in water to prepare a 21% by weight aqueous solution, and 6% by weight of hydroxyapatite powder (particle size 50 to 300 Å) was added to this aqueous solution.
Mixed and degassed. The raw material solution prepared in this manner was supplied at room temperature to the apparatus used in Example 1, and extruded at a pressure of 1.4 kg/cm ² . At the same time, air was ejected from the air gap at a speed of 500 m/s to generate a fiber flow. formed. This fiber flow is applied to a far infrared heater (wavelength 2~
While heating the fiber stream at a heater temperature of 400° C. from both sides of the fiber stream, the fibers were sprayed onto a net-type collection belt to evaporate and remove moisture, thereby obtaining a flocculent body of hydroxyapatite bonded with pullulan. When the obtained flocculent material was heated at a temperature increase rate of 50°C/hour and baked at 1400°C for 2 hours, the pullulan disappeared and the average fiber diameter was 3 μm.
An apatite flocculent body with an average fiber length of 30 mm was obtained. When this was examined by infrared absorption analysis, it was confirmed that the hydroxyl groups of hydroxyapatite had disappeared.

Example 2 The average fiber diameter after firing was 15 μm in the same manner as in Example 1 except that the amounts of pullulan powder, hydroxyapatite powder, and water used were 19% by weight, 31% by weight, and 50% by weight, respectively. , average fiber length 70mm
A flocculent body consisting of hydroxyapatite was obtained.

Example 3 The same procedure was used as in Example 1 except that polyvinyl alcohol with a molecular weight of 190,000 was used as the binder, and the average fiber diameter after firing was 7 μm and the average fiber length was
A flocculent body made of hydroxyapatite with a diameter of 65 mm was obtained.

[Brief explanation of drawings]

FIG. 1 is a schematic side view showing an example of an apparatus used for manufacturing the apatite flocculent of the present invention. 2: Raw material tank, 5: Spinning nozzle, 7: Air nozzle, 8: Fine fiber flow, 9: Infrared heater, 1
0: Dehydrated fine fiber stream, 11: Net type collection belt, 12: Apatite flocculent.

Claims (1)

[Scope of Claims] 1. Apatite flocculent material consisting essentially of hydroxyapatite. 2. The apatite floc-like material according to claim 1, wherein the average fiber diameter is 1 μm to 30 μm, and the average fiber length is 2 mm to 1000 mm.