JPH01124684A - Composite apatite fiber molded product and production thereof - Google Patents

Abstract

PURPOSE: To obtain a complex apatite-basd fibrous molded product hardly straggling, flexible and comprising a lyophilized material of apatite-based fibrous molded product impregnated with an organic macromolecular liquid having a biocompatibility. CONSTITUTION: This molded product is obtained by preparing an aqueous suspension comprising: a solution containing 0.5 to 99 wt.% (based on the complex molded product) of a biocompatible organic macromolecular substance e.g. collagen, alginic acid, chitosan, lebrun or PVA; and an apatite compound e.g. apatite hydroxide, by forming a fiber from the suspension through a nozzle, by reducing the water content of the fiber to <=10 wt.% for solidification by heating it via e.g. infrared heater, followed by burning it at 500 to 1,200 deg.C. The molded product is improved in operating maneuverability because of its flexibility and little straggling and extremely useful for treatment for absence of bone.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a novel composite apatite-based fibrous molded product and a method for producing the same.

[Prior Art and Its Disadvantages] Defects or voids may be created in bones due to surgery for fractures or bone tumors. To fill such defects and voids, autologous bone taken from other parts of the patient or allogeneic bone taken from the patient's relatives has been used for a long time. However, according to this method, it is necessary to perform surgery on a part other than the injured part to collect bone, which places a heavy burden on the patient or his/her next of kin. Furthermore, if the defect or void is large, it is often not possible to collect a sufficient amount of bone.

For this reason, one artificial bone filler has been developed and used. Metals and ceramics are known as materials for artificial fillers, but among these, calcium phosphate compounds are particularly preferred from the viewpoint of biocompatibility. Among calcium phosphate compounds, it is known that hydroxyapatite, which is a bone component, is particularly preferred. Conventionally developed hydroxyapatite fillers include granular,
There are powder forms (JP-A-56-54841), porous and fibrous molded products (JP-A-62-221:158).However, granular, powder and porous products are difficult to manipulate during surgery. There are difficulties in sexual workability. What are the disadvantages of granular, powder and porous materials? Although the problem has been largely solved in fibrous molded products, conventional hydroxyapatite-based fibrous molded products have the disadvantage that the strength of the molded product is low and the fibers easily come apart during surgery.

[Problems to be Solved by the Invention] Therefore, an object of the present invention is to provide a soft and pliable apatite-based fibrous molded product in which the fibers are loose.

Further, the purpose of this invention is to obtain such apatite-based m! i
An object of the present invention is to provide a method for manufacturing a shaped molded article.

[Means for Solving the Problems] As a result of intensive research, the inventors of the present application found that by freeze-drying an apatite-based fibrous molded product impregnated with a solution of a biocompatible organic polymer substance, The present invention was completed based on the discovery that it is possible to obtain a soft and pliable apatite-based fibrous molded product in which the fibers do not easily come apart.

That is, the present invention provides a composite apatite-based fibrous molded product comprising a freeze-dried product of an apatite-based MA fibrous molded product impregnated with a solution of a biocompatible organic polymer substance.

[Effects of the Invention] According to the present invention, a composite apatite-based fibrous molded product in which the apatite fibers are separated and the operability and workability during surgery are improved is provided. The composite apatite fibrous molded product of the present invention is soft and pliable, so it adapts to the shape of complex bone defects and voids, and has a high osteogenic ability, making it an excellent filling material for bone defects and voids. It can be used as a material.

[Detailed Description of the Invention] The apatite-based fibrous molded product used in the composite apatite-based fibrous molded product of the present invention is 1, for example, JP-A-62-2
21358, ie, fibrous moldings, for example nonwoven, cotton, cotton wool or roving, formed from fibers containing an apatite compound. The apatite compound is preferably hydroxyapatite, and the fiber preferably contains hydroxyapatite in an amount of 25% by weight or more, more preferably 50% by weight or more. From a biocompatibility point of view, it is preferable for the fiber to consist essentially only of hydroxyapatite, in which case the strength of the fiber is reduced.

In order to increase the strength of the fiber, one such as Ca(
A calcium phosphate compound such as po, )2, water glass, etc. can be included as a reinforcing agent. Among reinforcing agents, calcium phosphate compounds are preferred from the viewpoint of biocompatibility. The content of reinforcing agents is usually less than 25% by weight.

Additionally, the fibers may contain water. The water content is usually less than 50% by weight.

The diameter of the fibers constituting the apatite-based fibrous molded product is not particularly limited, but is usually 1 to 50 m, preferably 1 to 20 pL11. There is also no particular limit to the weight per area of the fibrous molded product, but it is usually between 5 gem" and 5.
00 gem”.

On the other hand, the organic polymeric substance used in the composite apatite-based miscellaneous molded article of the present invention may be water-soluble or water-insoluble as long as it is biocompatible, and water-soluble substances are preferred. Examples include collagen, fibroin, fibrin, alginic acid, chitosan, hyaluronic acid,
Mention may be made of chondroitin sulfate, agarose, pullulan, polyvinyl alcohol and hydroxypropyl cellulose, and preferred examples of water-insoluble substances include chitin, polyhydroxybutyrate, polyalkylene carbonate, polylactic acid and polyacetic acid.

The molecular weight of these organic polymer substances is not particularly limited, but is usually about 500 to 10,000.

The content of the organic polymer substance in the composite apatite-based fibrous molded product of the present invention is not particularly limited, but is usually 0.5% to 99% by weight, preferably 2% to 50% by weight, More preferably, it is 5% to 30% by weight.

The composite fibrous molded article of the present invention can be manufactured as follows.

First, an apatite-based m-fibrous molded product is prepared. Apatite-based fibrous molded products are, for example, JP-A-62-221:158.
It can be manufactured by the method described in No. That is, it can be produced by forming a fibrous material by a solution method using an organic binder and firing it at a temperature of 500°C to 1300°C.

It is preferable that the binder used in this method satisfies at least two conditions: it is harmless to living organisms and it is water-soluble.There are many polymer compounds that satisfy these conditions, but polyvinyl alcohol, carboxymethyl cellulose, In addition to hydroxypropylcellulose and collagen, polysaccharides such as pullulan and chitin are preferred, and pullulan is particularly preferred.The average molecular weight of these polymer compounds is preferably 2 to 2 million, particularly 5 to 10
00,000 is preferable. These polymer compounds can be used alone or in combination of two or more.

The raw material used in this production method, for example, an apatite compound such as hydroxyapatite, preferably has a particle size of 5n~lp.
It is in the form of ultrafine particles of Lm. Although there is no particular restriction on the shape of the fine particles, rod-like shapes are preferred. Such an apatite compound can be produced, for example, by gradually dropping an aqueous phosphoric acid solution into an alkaline solution (pH 7 to 11) containing calcium ions.

In the method for producing an apatite-based fibrous molded product, an aqueous suspension containing the above-mentioned binder and an apatite compound is used as a raw material, and the composition of this raw material is usually 10 to 10% water.
90% by weight, preferably 50-70% by weight, more preferably 60-65% by weight, apatite compound: 5-70%
% by weight, preferably 10-50% by weight, more preferably 15-35% by weight, binder = 5-40% by weight, preferably 10-30% by weight, more preferably 10-2
It is 0% by weight. If the apatite compound is less than 5% by weight, the strength of the fibrous material will be low, so it is not preferable.
If it exceeds 70% by weight, the viscosity increases, which is not preferable.

In this method, organic carboxylic acid surfactants, plasticizers, softeners, etc. are added as necessary to increase the fluidity of the raw materials and improve the dispersion of the apatite compounds in the raw materials. You can also do that. It is also possible to add an antifoaming agent. These contents are usually 0 relative to the weight of the raw material.
．． 011 to 5%. Further, when the reinforcing agent is included in the fiber, the reinforcing agent is dispersed in the raw material. These various additives must be selected from those that are harmless to living organisms.

The raw material liquid is preferably prepared at a temperature of about 20°C to 70°C.

The apatite-based fibrous molded product can be produced using the above-mentioned raw material liquid, for example, by the following method.

First, the raw material liquid is extruded through a die in which a plurality of melt spinning nozzles having pores are arranged linearly in the width direction, and at the same time, the gas velocity is increased from around the nozzles to about 5 to about 1.
A fiber stream consisting of drawn fine fibers is formed by ejecting a gas, such as air, at a temperature of 20° C. to about 60° C. at a rate of 000 μ/sec. In this case, the diameter of the fiber depends on the velocity of the ejected gas, and is usually 1 to about 50 JLs+, preferably about 1 to about 20 JLs+.
It is adjusted to fall within the range of 舊■. If the gas velocity is high, the fiber diameter will be small; if the gas velocity is low, the fiber diameter will be large. When the gas velocity is 100 ports/sec, the diameter is usually 1 gm,
At 300 m/s, the diameter is usually 3 to 5 JLts,
At 30 m/sec, fibers with a diameter of about 2 mm are usually formed.

Next, this fine fiber stream is heated by a heating device installed under the die, such as an infrared heater, a far-infrared heater, or a microwave heater, to reduce the water content in the fibers to 10% by weight or less, preferably It is evaporated to about 7% by weight or less and solidified. If moisture removal is insufficient, a fibrous material consisting of fine fibers cannot be obtained.

The heating temperature for the fiber flow depends on the extrusion amount of the raw material liquid,
It is selected depending on the balance of the temperature of the ejected gas and the air volume, etc., but it is usually in the range of 200° C. to 500° C. in terms of heater temperature (80° C. to about 150° C. in terms of fiber flow temperature). If the heating temperature is made higher than necessary, the binder will decompose during the heating process, which is not preferable.

The fine fiber stream that has been drawn as described above and from which water has been removed is intertwined and dropped onto a moving collection device, such as a net-type rotating drum, a moving belt, etc.
Form an l-shaped object. In this case, when the fiber stream is dropped onto the contact point of two rotating net-type collection trams, the fibers are intertwined or arranged in the thickness direction (i.e., three-dimensionally) of the fibrous material. A bulky product, that is, a cotton-like or absorbent cotton-like fibrous material is obtained.In addition, the fiber stream is sprayed onto a part other than the contact point of the collection tram or a flat collection belt, etc. In some cases, a nonwoven fabric in which fibers are arranged parallel to a plane (that is, two-dimensionally) can be obtained.Furthermore, roving-like fibers can be formed using a device in which melt spinning nozzles are arranged circumferentially. can.

Furthermore, the basis weight of the fibrous material can be changed from 5 g/112 to 500 g/112 by changing the moving speed of the collecting device.
It can be arbitrarily adjusted within the range of g/-2.

The thus obtained fibrous material bound by the binder is heated from about 500°C to about 1300°C, preferably from about 600°C to about 1200°C, more preferably from about 650°C to about 1.00°C. The apatite-based fibrous molded article used in the composite apatite-based fibrous molded article of the present invention can be obtained by firing at a temperature of .degree. C. to burn off the binder. Calcining at a temperature of 1300° C. or higher is not preferable because the hydroxyl groups of the apatite compound will disappear. 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 is almost negligible. Therefore, if necessary, the amount of apatite compound in the fibrous material can be adjusted by adjusting the firing temperature to about 1100°C to 1300°C. In this case, (:az(PO4)i) is produced and mixed with the apatite compound, which can also improve the strength of the fiber.

Next, the apatite-based fibrous molded product thus obtained is impregnated with a solution of the above-mentioned biocompatible organic polymer substance. Impregnation can be carried out by immersing the fibrous molding in a solution of the organic polymeric substance, or by spraying or coating the fibrous molding with a solution of the organic polymeric substance. The concentration of the organic polymer substance in the solution is not particularly limited, but is usually 0.1% by weight to 1 liter.
It is about 0% by weight. The amount of the organic polymeric substance solution to be impregnated may be selected so that the content of the organic polymeric substance in the composite fiber molded product after the solvent is removed by the freeze-drying process described below falls within the above range. Further, the solvent for the organic polymeric substance solution may be water if the organic polymeric substance is water-soluble, and if it is water-insoluble, any good solvent for the substance may be used.

Next, the apatite-based fibrous molded article impregnated with the organic polymer substance solution in this manner is freeze-dried. Freeze-drying can be carried out using a reprint freeze-drying device.

The freeze-drying process is performed until the solvent of the organic polymer substance solution is completely removed.In this way, the freeze-drying process is performed until the solvent is completely removed, so if only water-soluble organic polymer substances are used, Therefore, water-insoluble organic polymer substances can also be used. In particular, since the above-mentioned water-insoluble substances are not only harmless to living organisms but also biodegradable polymers, they can exhibit even more excellent effects when used as bone fillers.

The composite apatite-based fibrous molded product of the present invention thus obtained is soft and pliable without the apatite-based fibers coming loose in a dry state that does not contain a solvent.

Examples 1 to 5 9% by weight of pullulan powder with an average molecular weight of 200,000, 42% by weight of hydroxyapatite powder (particle size 5 to B0n), 1% by weight of dispersant (organic carboxylic acid surfactant), 48% by weight of water % was kneaded to uniformly disperse hydroxyapatite in the pullulan aqueous solution, and degassing was performed. This solution was prepared at room temperature with a diameter of 0
．． The gas is discharged from the spinning nozzle No. 3, and the gas is discharged from the gas discharge hole installed adjacent to the spinning hole at a speed of 300 m/sec to stretch the fiber and form a fiber stream, and this fiber stream is directed under the nozzle. The obtained flocculent body was heated with an infrared heater (2 to 50 JL11), evaporated to remove moisture, and blown onto a net-type collection drum.
It was heated to 0°C and baked at this temperature for 1 hour.

The obtained hydroxyapatite flocculent has an average fiber diameter of 5
The basis weight in μ amount was approximately 200 g/■2.

To 3 g of the hydroxyapatite flocculent thus obtained,
100 ml of a solution containing the organic polymer substances shown in the table below and the concentration shown in the table in the solvent shown in the same table was impregnated and freeze-dried.

A composite hydroxyapatite fibrous molded product having the composition shown in the table was obtained. All of the molded products obtained retained the shape and texture of hydroxyapatite fibers, and were soft and supple.

Claims (6)

[Claims] (1) A composite apatite-based fibrous molded product comprising a freeze-dried product of an apatite-based fibrous molded product impregnated with a solution of a biocompatible organic polymer substance. (2) The composite apatite-based fibrous molded product according to claim 1, wherein the apatite-based fiber contains 25% by weight or more of hydroxyapatite. (3) The composite apatite-based fibrous molded product according to claim 2, wherein the apatite-based fiber contains 50% by weight or more of hydroxyapatite. (4) The biocompatible organic polymer substances include collagen, fibroin, fibrin, alginic acid, chitosan, hyaluronic acid, chondroitin sulfate, agarose,
The composite apatite system according to any one of claims 1 to 3, which is pullulan, polyvinyl alcohol, hydroxypropyl cellulose, chitin, polyhydroxybutyrate, polyalkylene carbonate, polylactic acid or polybutyric acid. Fibrous moldings. (5) The content of the organic polymer substance in the composite apatite-based fiber molded product is from 0.5% to 99% by weight, according to any one of claims 1 to 4. Composite apatite-based fibrous molded product. (6) A method for producing a composite apatite-based fibrous molded product, which comprises impregnating the apatite-based fibrous molded product with a solution of a biocompatible organic polymer substance and freeze-drying the solution.