JP4463719B2 - Organic-inorganic composite porous body, method for producing fibrous organic substance, and method for producing organic-inorganic composite porous body - Google Patents

Description

  The present invention relates to an organic-inorganic composite porous body, a method for producing a fibrous organic material, and a method for producing an organic-inorganic composite porous body, and more particularly, a biomaterial, in particular, a filling material for teeth or bones, a packing material such as a column. The present invention relates to an organic-inorganic composite porous material that can be widely used as an environmental material for the purpose of adsorbing pollutants, a method for producing a fibrous organic material, and a method for producing an organic-inorganic composite porous material.

  To date, hydroxyapatite sintered bodies, calcium phosphate hydrated hardened materials, polylactic acid screws that are biodegradable resins, and the like have been developed as bone and tooth restoration materials, and these have already been put into practical use. In recent years, as a next-generation biomaterial, a material having a pore structure in which a living tissue such as a cell can easily invade, excellent in biocompatibility, and gradually absorbed in the living body is desired. Such a material is also expected as a filling material using regenerative medicine in which cells and materials are combined. In addition, packing materials such as columns and environmental materials for the purpose of removing pollutants, etc., have a continuous pore structure that allows the permeation of liquids to be separated or gases smoothly, and has a high adsorption capacity. A material containing is useful.

  Examples of such materials include highly bioactive calcium phosphate compounds, biodegradable resins such as polylactic acid having in vivo degradation and absorbability, and composite materials thereof. Various such porous materials have been developed in the past.

  One of them is a calcium phosphate-based porous material obtained by using a thermally decomposable resin or the like as a pore forming agent. This calcium phosphate porous material has a problem that since the pores are spherical, the path diameter between the continuous vent holes is reduced, and the pore diameter needs to be increased more than necessary to increase the path diameter.

  On the other hand, an organic-inorganic composite porous body (Patent Document 1) in which a fibrous biodegradable resin containing calcium phosphate is welded is mentioned as a porous body having good continuous air permeability.

JP 2003-159321 A

  In the porous body described in Patent Document 1, it is necessary to previously mix a calcium phosphate compound to be added to the porous body in order to impart bioactivity or the like to the biodegradable resin. Accordingly, the surface of the material is not exposed to a large amount of the calcium phosphate compound surface, and the calcium phosphate characteristics such as bioactivity cannot be sufficiently imparted to the amount added. That is, in practice, most of the calcium phosphate that contributes to biological activity is present inside the resin, and the degree of exposure of calcium phosphate to the amount added is very low, which is not preferable.

  On the other hand, a calcium phosphate porous body using apatite whiskers is also known as a conventional technique (Non-patent Document 1).

  Since apatite whiskers have different properties of the substances adsorbed on each crystal face of the whisker, materials containing apatite with controlled crystal morphology are very useful as biomaterials or adsorbing materials. For example, regarding biomaterials, it is said that a specific crystal surface of apatite promotes the adsorption and proliferation action of living cells and the like. Are proliferating and are expected to be used as a material for promoting the repair of a defect in a living body, and as a material for regenerative medicine in which cells are cultured in the material in advance and supplemented in the living body. In addition, the apatite whisker can be an adsorbent with high selectivity as an environmental material by controlling a crystal plane that is advantageous for adsorption of a specific substance.

Chemical Industry, September 1993, p710-717

  However, since this porous body is produced by sintering apatite whiskers, the thermal decomposition of the apatite whiskers occurs during sintering, and there is a problem that the composition of the apatite constituting the porous body is limited. . For example, when the Ca / P molar ratio of apatite is smaller than 1.67, which is the stoichiometric ratio of apatite, the apatite may be thermally decomposed to produce calcium phosphate other than apatite.

  Further, a porous body only of biodegradable resin as in Patent Document 2 has already been developed. This is useful as a biodegradable porous material for living organisms when applied to a site that does not require application of biologically active calcium phosphate or the like. Since the resin production method is a spray spraying method, a special fiber production apparatus is required. In general, in order to produce resin fibers, a special apparatus such as a wet spinning apparatus is required. The manufacturing method of the fibrous biodegradable resin containing calcium phosphate of Patent Document 1 is also the same. In particular, in Patent Document 1, since a porous body is obtained by dispersing calcium phosphate in a resin dissolved in a solvent in advance, producing fibers by a spinning device such as a spray, and welding them, the resin is contained in the resin. There are problems in production such as spray clogging due to the calcium phosphate particles contained and fibers being cut short. Further, since the fiber obtained by a conventional spinning device or the like is a long fiber, it is generally suitable for a material such as a sheet-like non-woven cloth, but is not suitable for manufacturing a block-like material. In particular, a manufacturing method such as a spray spray method is not suitable for manufacturing a block-like material, and thus the shape of the material is limited.

JP 2002-315819 A

The problem to be solved by the present invention is to solve the above-mentioned problems, and has organic pores in which the fibrous calcium phosphate is dispersed in a state having continuous air holes and the fibrous calcium phosphate is almost exposed on the pore surface and the porous body surface. An object is to provide an inorganic composite porous body and a method for producing the organic-inorganic composite porous body.

As means for solving the problems,
Claim 1
An organic-inorganic composite porous material comprising fibrous calcium phosphate and fibrous organic matter, wherein the fibrous organic matter and at least part of the fibrous calcium phosphate are intertwined,
Claim 2
The organic-inorganic composite porous body according to claim 1, wherein at least a part of at least a part of the entanglement between the fibrous organic substance and the fibrous calcium phosphate is joined.
Claim 3
The organic-inorganic composite porous body according to claim 1 or 2, wherein the porosity is at least 30%.
Claim 4
The organic organic-inorganic composite porous body according to any one of claims 1 to 3, wherein the fibrous organic matter is a biodegradable resin.
Claim 5
The biodegradable resin is at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid, and polycaprolactone, and / or at least one selected from the group consisting of lactic acid, glycolic acid, and caprolactone. The organic-inorganic composite porous body according to claim 4, comprising a copolymer obtained using a monomer.
Claim 6
The organic-inorganic composite porous body according to any one of claims 1 to 5, wherein the fibrous calcium phosphate is an apatite whisker.
Claim 7
It is a method for producing an organic-inorganic composite porous body characterized by mixing fibrous organic matter and fibrous calcium phosphate, and joining the fibrous organic matter and at least part of the fibrous calcium phosphate by welding,
Claim 8
The method for producing an organic-inorganic composite porous body according to claim 7, wherein the welding is achieved by melting a fibrous organic substance.
Claim 9
The method for producing an organic-inorganic composite porous body according to claim 7 or 8, wherein the fibrous calcium phosphate is an apatite whisker.
Claim 10
The method for producing an organic-inorganic composite porous body according to any one of claims 7 to 9, wherein the fibrous organic matter is a biodegradable resin.
Claim 11
The biodegradable resin is at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid, and polycaprolactone, and / or at least one selected from the group consisting of lactic acid, glycolic acid, and caprolactone. The method for producing an organic-inorganic composite porous body according to claim 10, comprising a copolymer obtained using a monomer.
Claim 12
The fibrous organic matter is obtained by mixing a solvent solution obtained by dissolving an organic matter in a solvent, a water-soluble polymer and a water-soluble polymer coagulant to obtain a mixture, and stirring the mixture. It is a fibrous organic substance obtained by the manufacturing method of the fibrous organic substance characterized by including the process of removing the solvent component in the said liquid mixture, The said any one of Claims 7-11 characterized by the above-mentioned. Is a method for producing an organic-inorganic composite porous material according to claim 1,
Claim 13
The method for producing an organic-inorganic composite porous body according to claim 12, wherein the water-soluble polymer is polyvinyl alcohol.
Claim 14
The method for producing an organic-inorganic composite porous body according to claim 12 or 13, wherein the organic substance is a biodegradable resin.
Claim 15
The biodegradable resin is at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid, and polycaprolactone, and / or at least one selected from the group consisting of lactic acid, glycolic acid, and caprolactone. The method for producing an organic-inorganic composite porous body according to claim 14, comprising a copolymer obtained using a monomer.
Claim 16
The method for producing an organic-inorganic composite porous body according to any one of claims 12 to 15, wherein the water-soluble polymer coagulant contains a condensed phosphate and / or a sulfate.
Claim 17
The organic-inorganic composite porous body according to claim 16, wherein the condensed phosphate contains at least one selected from the group consisting of sodium pyrophosphate, sodium tripolyphosphate, and sodium hexametaphosphate. Is the way
Claim 18
The organic-inorganic composite porous body according to any one of claims 12 to 17, wherein the solvent is at least one selected from the group consisting of methylene chloride, chloroform, dichloroethane, and ethyl acetate. Is a manufacturing method of
Claim 19
A dispersion step in which the apatite whisker disperses a calcium phosphate gel compound that produces orthophosphoric acid and protons at 80 to 250 ° C. in a solvent containing at least one of water and a hydrophilic organic solvent; In which the dispersion is heated to 80 to 250 ° C., the pH of the dispersion before heating is 9 or less, and the pH of the dispersion after heating is 3.9 to 9. The method for producing an organic-inorganic composite porous body according to any one of claims 9 to 18, wherein the apatite whisker is obtained.
Claim 20
The method for producing an organic-inorganic composite porous body according to any one of claims 7 to 19, wherein soluble particles are added to a mixture of the fibrous organic substance and fibrous calcium phosphate.
Claim 21
21. The method for producing an organic-inorganic composite porous body according to claim 20, wherein at least a part of the fibrous organic material and the fibrous calcium phosphate are joined by welding, and then the soluble particles are removed with a solvent. ,
Claim 22
The method for producing an organic-inorganic composite porous body according to claim 20 or 21, wherein the soluble particles are water-soluble polysaccharides and / or water-soluble inorganic salts.

  The organic-inorganic composite porous body of the present invention includes fibrous calcium phosphate and fibrous organic matter, entangles the fibrous organic matter and at least part of the fibrous calcium phosphate, and further joins a part of the entanglement. Therefore, most of the fibrous calcium phosphate contained in the organic-inorganic composite porous body is present at a high degree of exposure on the inner surface of the pores and the surface of the organic-inorganic composite porous body, and therefore In addition, the degree of exposure of the fibrous calcium phosphate contained in the organic-inorganic composite porous body is high, and the porosity is high, including pores distributed in the pore diameter range of 1 to 1000 μm, and rich in communication. It has a pore structure. Such an organic-inorganic composite porous body is a porous body having excellent bioactivity and adsorbability, and a high degree of exposure to fibrous calcium phosphate. Therefore, it is used for medical applications and environmental materials. be able to.

  When the fibrous organic matter is a biodegradable resin, when the organic-inorganic composite porous body is filled in a living body, the biodegradable resin is gradually decomposed, and most of the organic-inorganic composite porous body is It is replaced with living tissue and repairs the defect in the living body. Therefore, according to the present invention, it is possible to provide an organic-inorganic composite porous body suitable for medical use because of its good biocompatibility. Further, when the organic-inorganic composite porous body is used as an industrial material such as an environmental material, it can be treated by biodegradation after use, so that it becomes an environmentally friendly material.

  The biodegradable resin may be at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid, and polycaprolactone, and / or at least one selected from the group consisting of lactic acid, glycolic acid, and caprolactone. In the case of including a copolymer obtained by using the above monomer, an organic compound having various properties and properties such as a hard one and a sponge-like one can be obtained by appropriately selecting the kind of the polymer and the copolymer. -An inorganic composite porous body can be provided. The biodegradable resin may be a mixture with other biodegradable resins.

  According to the present invention, since the organic-inorganic composite porous material contains fibrous calcium phosphate, fibrous calcium phosphate can be contained without hindering the connectivity of pores formed by the fibrous organic material. In addition, since the fibrous calcium phosphate is fibrous, the entanglement between the fibrous calcium phosphates or the fibrous organic matter is improved, so that the amount of the fibrous organic matter can form at least a porous body. The content of the calcium phosphate can be increased.

  According to the present invention, an organic-inorganic composite porous body containing an apatite whisker as the fibrous calcium phosphate can be provided. In this organic-inorganic composite porous material, apatite can incorporate various ions into calcium ion sites, phosphate ion sites, or hydroxyl sites in the crystal. Since the properties of the apatite change due to, apatite whiskers suitable for the purpose of the porous body can be contained. For example, phosphate apatite or carbonate apatite in which carbonate ion is substituted at the hydroxyl site is faster in vivo than hydroxyapatite, and fluorine apatite in which fluoride ion is substituted at the hydroxyl site is water Since it is chemically stable as compared with acid apatite, it is possible to provide an organic-inorganic composite porous body containing an inorganic component controlled to have a dissolution rate suitable for an application site of a living body. In addition, by controlling the form of these whiskers, it is possible to obtain an environmental material having selective adsorptivity or a biological material advantageous for cell adhesion and proliferation.

The method for producing a fibrous organic matter referred to in the present invention is a step of mixing a solvent solution obtained by dissolving an organic matter in a solvent and an aqueous solution containing a water-soluble polymer and a water-soluble polymer coagulant to obtain a mixed solution. And a step of removing the solvent component in the mixed solution while stirring the mixed solution, so that a special apparatus such as a spray method or a wet spinning method which is a conventional technique is used. The organic matter can be easily made into a fibrous form without any problems. More say, in one preferred embodiment of the production method of the fibrous organic material, when an aqueous solution and an organic material containing a water-soluble polymer and a water-soluble polymer coagulant mixing a solvent solution obtained by dissolving in a solvent, solvent solution The aqueous solution is separated from the aqueous solution. After that, the solvent solution is dispersed in a spherical state in the aqueous solution by stirring, but gradually becomes spherical due to the action of the water-soluble polymer and the water-soluble polymer coagulant. The solvent solution is dispersed in a fibrous form. Thereafter, the solvent gradually dissolves in the aqueous solution, volatilizes, and is removed, so that the organic matter dissolved in the solvent is precipitated while maintaining its fibrous form, and as a result, dispersed in the aqueous solution. A fibrous organic material is obtained. The obtained fibrous organic matter can be taken out from the aqueous solution by separating the organic matter and the aqueous solution by filtration, centrifugation, or the like, and drying the separated organic matter. Thus, according to the manufacturing method of the said fibrous organic substance, a fibrous organic substance can be manufactured simply, without using a special apparatus. And this fibrous organic substance is not only used as a raw material for porous bodies, but can also be used as a raw material for other general non-woven fabrics. Further, in the method for producing the fibrous organic matter, short fibers having an average length in the range of several mm or less, particularly in the range of several μm to several mm can be obtained. It can be used for a wide variety of materials. Further, in the case of producing a composite, the short fiber obtained by the above production method can be uniformly mixed with other materials, and is thus excellent as a raw material for producing the composite.

  The water-soluble polymer in the method for producing fibrous organic matter is not particularly limited as long as the polymer is condensed at the interface between the solvent and the aqueous solution by the water-soluble polymer coagulant coexisting in the aqueous solution. From the viewpoint, polyvinyl alcohol is preferable. Polyvinyl alcohol is suitable as an additive because it is inexpensive and has a relatively high safety to living bodies even when it remains in the fibrous organic matter.

In this method for producing a fibrous organic material, when the organic material is a biodegradable resin , a fibrous organic material capable of suitably forming an organic-inorganic composite porous body having good absorbability in a living body can be produced. . From the group consisting of polylactic acid, polyglycolic acid, and polycaprolactone as biodegradable organic substances, as clarified in the explanation of the organic-inorganic composite porous material of the present invention and for the same reason clarified in the explanation. Preferred are at least one polymer selected or a copolymer obtained using at least one monomer selected from the group consisting of lactic acid, glycolic acid and caprolactone.

  In this method for producing a fibrous organic material, the water-soluble polymer coagulant preferably contains a condensed phosphate and / or sulfate. The water-soluble polymer coagulant has the function of coagulating the water-soluble polymer added to the aqueous solution, and a solvent solution in which an organic substance is dissolved is added to the aqueous solution to which the water-soluble polymer and the water-soluble polymer coagulant are added. , An additive that forms a water-soluble polymer film on the surface of the dispersed solvent solution when stirred. By forming this aqueous polymer film, the shape of the solvent solution being stirred is made fibrous due to the viscosity of the film, and organic substances are deposited in the aqueous solution while maintaining the shape. Therefore, this water-soluble polymer coagulant is an indispensable additive for the production method of fibrous organic matter. Such a water-soluble polymer coagulant is not particularly limited as long as the water-soluble polymer coagulates. In particular, when polyvinyl alcohol is used as the water-soluble polymer, condensed phosphate and / or sulfate. However, since the coagulation action is large, at least one condensed phosphate selected from the group consisting of sodium pyrophosphate, sodium tripolyphosphate, and sodium hexametaphosphate is more preferable.

  In this method for producing a fibrous organic material, when the solvent is at least one selected from the group consisting of methylene chloride, chloroform, dichloroethane, and ethyl acetate, these solvents are sparingly soluble in water, but slightly soluble Since the volatilization temperature is lower than that of water, the organic substance can be precipitated in a fibrous state in a good dispersion state in the aqueous solution.

  Furthermore, the organic-inorganic composite porous body according to the present invention includes a fibrous organic substance and fibrous calcium phosphate, and the fibrous organic substance and at least a part of the fibrous calcium phosphate are intertwined, and further part thereof. As long as the organic-inorganic composite porous body can be produced, the organic-inorganic composite porous body is preferably manufactured by the method of the present invention.

  According to the method for producing an organic-inorganic composite porous body according to the present invention, the fibrous organic substance and the fibrous calcium phosphate are mixed, and the fibrous organic substance and at least a part of the fibrous calcium phosphate are joined together by welding. An organic-inorganic composite porous body can be easily produced.

  As the welding, a part of the surface of the fibrous organic substance is dissolved by immersing the entangled fibrous organic substance and fibrous calcium phosphate in a solvent capable of dissolving the fibrous organic substance, and the fibrous organic substance A method of welding the fibrous organic substance whose surface is dissolved at the contact point with the fibrous calcium phosphate and the fibrous calcium phosphate, and joining the fibrous organic substance and the fibrous calcium phosphate by melting a part of the surface of the fibrous organic substance by heating. Among these, the welding method by heating is preferable. A welding method for bonding a fibrous organic substance and fibrous calcium phosphate by melting a part of the surface of the fibrous organic substance by heating (hereinafter, this method may be referred to as a heating welding method) is heated. Since it is realizable by selecting a means suitably, it is a simple and suitable method.

  In the method for producing an organic-inorganic composite porous body according to the present invention, by using fibrous calcium phosphate, a mixture in which fibrous calcium phosphate and fibrous organic matter are entangled can be easily obtained, and communication is more easily performed. An organic-inorganic composite porous body can be obtained. Further, since the number of contact points between the fibrous calcium phosphate and the fibrous organic matter is increased, it becomes easy to support the fibrous calcium phosphate in the organic-inorganic composite porous body, and the content of the fibrous calcium phosphate can be increased.

Furthermore, when an apatite whisker is selected as the fibrous calcium phosphate, various ions can be substituted into the crystal of the apatite whisker and the properties of the apatite can be changed. Therefore, the type and content of the substituted ion should be selected appropriately. Thus, an organic-inorganic composite porous body and the like in which the absorption rate in the living body is adjusted can be produced. Furthermore, in this production method, since the heat treatment is such that the fibrous organic materials or between the fibrous organic materials and the fibrous calcium phosphate is welded, the fiber is much lower than the sintering temperature as in the prior art. Even when apatite is used as the calcium phosphate, the organic-inorganic composite porous body can be produced without decomposition of the apatite.
In particular, the dispersion step of obtaining a dispersion by dispersing the calcium phosphate gel compound in which the apatite whisker generates orthophosphoric acid and proton at 80 to 250 ° C. in a solvent containing at least one of water and a hydrophilic organic solvent; A heating step of heating the dispersion to 80 to 250 ° C. in a sealed container, the pH of the dispersion before heating is 9 or less, and the pH of the dispersion after heating is 3.9 to 9 The apatite whisker obtained is a relatively large whisker having an average length of 10 μm or more. When such a large apatite whisker is employed, the average pore diameter is small. The organic-inorganic composite porous body having a continuous ventilation hole in any of the range of 1 μm to 1 μm to 100 μm can be easily manufactured. There is.

In this method for producing an organic-inorganic composite porous body, when the fibrous organic material is a biodegradable resin , an organic-inorganic composite porous body having good absorbability in a living body can be produced. In particular, as clarified in the explanation of the organic-inorganic composite porous body of the present invention and for the same reason clarified in the explanation, the biodegradable organic substance is composed of polylactic acid, polyglycolic acid, and polycaprolactone. Preference is given to at least one polymer selected from the group or a copolymer obtained using at least one monomer selected from the group consisting of lactic acid, glycolic acid and caprolactone.

  Moreover, an organic-inorganic composite porous body can be easily produced without using a special apparatus by using the above-described method for producing a fibrous organic substance as the fibrous organic substance here. Further, in the above production method, a pore forming agent such as a foaming agent and soluble particles is used in combination, and the present invention includes "a fibrous calcium phosphate and a fibrous organic substance, and the fibrous organic substance and at least a part of the fibrous calcium phosphate are An organic-inorganic composite porous body characterized by being intertwined and further being partially joined can be produced. In particular, the method of using soluble particles as the pore-forming agent can easily form pores of several tens of μm to several mm, and is suitable for adjusting the pore diameter and the porosity. This is because the mixture of soluble particles, fibrous organic matter, and fibrous calcium phosphate is immersed in a solvent in which only the soluble particles are substantially dissolved after joining the fibrous organic matter and a part of the fibrous calcium phosphate by heat treatment or the like. In this method, pores are formed by eluting only soluble particles. Since the porous body thus obtained has a mesh structure formed with fibrous calcium phosphate and fibrous organic matter in the skeleton between the pores formed with the pore-forming agent, It is a material with excellent communication. In addition, since the pore diameter formed by the pore-forming agent and the pore diameter of the mesh structure can be controlled, the pore diameter can be controlled according to the application. The pore diameter formed with the pore forming agent can be controlled by adjusting the particle diameter of the soluble particles. The pore diameter of the mesh structure can be controlled by the shape and size of the fibrous calcium phosphate and the fibrous organic substance, and further by the pressure at the time of forming the porous body. For example, as biomaterials, pores of several tens of μm or more in which biological tissues such as cells are likely to enter, and nutrients to penetrate into the materials in order to promote the growth of biological tissues such as cells inside the materials. A material having pores of several μm to several tens of μm in the skeleton is useful, and the present invention can provide a material having such pores. In addition, the product of the present invention can be combined with the mesh structure so that the characteristics of fibrous calcium phosphate can be efficiently utilized, so the wettability of the mesh structure of the skeleton is good and the permeability of nutrients is excellent. Can be a material.

  BEST MODE FOR CARRYING OUT THE INVENTION The best mode for carrying out the present invention will be described below, but the present invention should not be construed as being limited by the following description contents. The range easily conceivable or understandable based on this is also the scope of the present invention.

(1) Organic-inorganic composite porous body The organic-inorganic composite porous body according to the present invention includes fibrous calcium phosphate and a fibrous organic substance, and the fibrous organic substance and at least a part of the fibrous calcium phosphate are intertwined with each other. Furthermore, a part of the entanglement is joined.

  The fibrous organic material in the present invention may be any organic material that can be used as a biomaterial, a packing material such as a column, an environmental material for the purpose of adsorbing contaminants, and the like. An example of a fibrous organic material for a biomaterial is a biodegradable resin. This biodegradable resin is absorbed by a living body and forms bones and the like when an organic-inorganic composite porous body using the biodegradable resin is embedded in the living body.

  As a preferable example of the biodegradable resin, in particular, at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid, and polycaprolactone, or selected from the group consisting of lactic acid, glycolic acid, and caprolactone is used. A copolymer obtained using at least one monomer is preferred. In the present invention, as the fibrous organic substance, any one of the polymer and copolymer can be used alone, or at least two of the polymer and copolymer are used in combination. You can also

  Since these biodegradable resins have different biodegradation rates and strengths, they can be selected according to the purpose of use. Moreover, a sponge-like soft organic-inorganic composite porous body can be produced from a hard organic-inorganic composite porous body depending on the type and average molecular weight of the biodegradable resin used.

  The average fiber length of the fibrous organic matter is usually 10 μm at the most, and preferably 10 to 10,000 μm. The average fiber length of the fibrous organic material can be easily measured by photographing the fibrous organic material using an electron microscope or an optical microscope. Further, the fibrous organic matter can be used together with an organic matter such as a spherical shape or an indefinite shape. In that case, the fibrous organic matter is 50% by mass or more, preferably 80% by mass with respect to the total of the fibrous organic matter and other organic matter. % Or more is desirable. Further, the fiber diameter does not have to be uniform, and the effect of the present invention is not lost by the non-uniform diameter. Therefore, the fiber in the present invention may have a shape in which one end is round and thick and the other end is thin and sharp, and such a fiber is also fibrous.

  The content of the fibrous organic substance such as the biodegradable resin with respect to the organic-inorganic composite porous body is usually 10 to 99% by mass, particularly 20 to 99% by mass, and the content is appropriately determined from these ranges. It is determined. If the content of the fibrous organic material is less than the lower limit, the strength of the organic-inorganic composite porous body may be reduced, and handling properties may be reduced.

  Fibrous calcium phosphate in the present invention is hydroxyapatite, carbonate apatite, fluorapatite, calcium hydrogen phosphate, calcium hydrogen phosphate hydrate, α-type tricalcium phosphate, β-type tricalcium phosphate, tetracalcium phosphate, Any one or more of primary calcium phosphate and primary calcium phosphate hydrate may be used. Since these calcium phosphates have different solubility depending on each compound, for example, when used as a biomaterial, they can be selected and used from among these in order to adjust the absorption substitution rate.

  The form of fibrous calcium phosphate is usually fibrous. As the fibrous calcium phosphate, an apatite whisker is preferable.

  Apatite whiskers can incorporate various ions into calcium ion sites, phosphate ion sites, or hydroxyl sites in the crystal, and the properties of the apatite whiskers change depending on the amount and type of each substituted ion. In particular, carbonate apatite with carbonate ions substituted at phosphate ion sites and / or hydroxyl sites is faster in vivo than hydroxyapatite, and fluorine apatite with hydroxyl ions substituted at hydroxyl sites is Since it is chemically stable as compared with hydroxyapatite, it is possible to provide an organic-inorganic composite porous body containing an inorganic component controlled to have a dissolution rate suitable for the application site of a living body. In addition, since the adsorption characteristics of apatite crystals are different on each crystal face, a large amount of each crystal face can be selectively exposed by controlling the form of the apatite whiskers to be used. It becomes possible to control the characteristics. That is, an environmental material having selective adsorptivity and a biomaterial having characteristics advantageous for cell adhesion and proliferation can be obtained.

  The length of this fibrous calcium phosphate such as apatite whisker is not particularly limited, but in order to make the organic-inorganic composite porous body have a more porous structure, the average major axis length is short. Is preferably 10 μm, particularly preferably in the range of 10 to 1000 μm. The average aspect ratio of the fibrous calcium phosphate is not particularly limited, but is preferably 1 to 1000, and particularly preferably 5 to 500. The average major axis length and average aspect ratio of fibrous calcium phosphate can be easily measured by observation with an electron microscope or an optical microscope.

Such fibrous calcium phosphate can be suitably manufactured by using a method of extruding and sintering calcium phosphate mixed with a binder or the like, a hydrothermal method, or the like, but is not limited thereto. Moreover, the tricalcium phosphate fiber obtained by heat-treating the apatite whisker obtained by the hydrothermal method can also be suitably used as the fibrous calcium phosphate in the present invention.
A suitable fibrous calcium phosphate such as apatite whisker is a dispersion obtained by dispersing a calcium phosphate gel compound that generates orthophosphoric acid and protons at 80 to 250 ° C. in a solvent containing at least one of water and a hydrophilic organic solvent. And a heating step of heating the dispersion to 80 to 250 ° C. in a closed container, the pH of the dispersion before heating is 9 or less, and the pH of the dispersion after heating is 3.9 to 9 Can be manufactured. A calcium phosphate gel compound that generates orthophosphoric acid and protons at 80 to 250 ° C. has a relatively high efficiency of 10 μm even if the average major axis length is short, and particularly within the range of 10 μm to 100 μm. This is because it is possible to easily obtain the apatite whisker. Examples of the hydrophilic organic solvent include lower alcohols having 1 to 3 carbon atoms such as methanol and ethanol, ethers such as dimethyl ether, diethyl ether and methyl ethyl ether, and water-soluble ketones such as acetone. . In the heating step, the dispersion is overheated to the temperature range in order to decompose the calcium phosphate gel and generate orthophosphoric acid and protons. In addition, the pH of the dispersion before heating is 9 or less, and when the pH is higher than that, the average major axis length is 10 μm even if it is short, and in particular, it is in the range of 10 μm to 100 μm. This is because a whisker cannot be obtained. The reason why the pH of the dispersion after heating is in the above range is that when the pH is lower than 3.9, a large amount of calcium hydrogen phosphate is generated as a by-product, and the pH is higher than 9. In this case, even if the average major axis length is short, it is 10 μm, and in particular, it becomes impossible to obtain an apatite whisker in any of the range of 10 μm to 100 μm.
As the calcium phosphate gel compound, it is desirable to use condensed calcium phosphate gel, which hydrolyzes at 80 to 250 ° C. to generate orthophosphoric acid and protons. In particular, as the condensed calcium phosphate gel, it is preferable to use calcium tripolyphosphate or calcium pyrophosphate. Moreover, in order to adjust the molar ratio of calcium and phosphorus, excessive calcium ions, condensed phosphate ions, or the like may be contained in the gel.

  The content of fibrous calcium phosphate such as apatite whisker with respect to the organic-inorganic composite porous body is usually 1 to 90% by mass, preferably 1 to 80% by mass, and there is no particular limitation within these ranges. In the organic-inorganic composite porous body, since the surface of the fibrous calcium phosphate is almost exposed by having the continuous air holes, bioactivity and adsorption ability can be effectively imparted even if the content of the fibrous calcium phosphate is small. .

  The organic-inorganic composite porous body according to the present invention has continuous air holes due to the above characteristics. The porosity of the organic-inorganic composite porous body having continuous air holes is 30% or more, preferably 50 to 95%, particularly preferably 60 to 90%. Moreover, the pore diameter of this organic-inorganic composite porous body is normally distributed within a range of 1 to 1000 μm. Here, the porosity can be calculated from the outer dimensions and weight of the porous body, and the pore diameter can be measured by, for example, a mercury porosimeter.

  When the organic-inorganic composite porous body according to the present invention is used as a biomaterial, the organic-inorganic composite porous body has a pore diameter distribution in the range of 50 to 50 μm in terms of the volume ratio of the pores. In addition, it is preferable that the porosity is 50% or more. Here, the pore size distribution can be measured by, for example, a mercury porosimeter.

When the fracture surface of the organic-inorganic composite porous material according to the present invention is observed with an SEM, particularly when an apatite whisker is used, the fibrous organic matter and the fibrous calcium phosphate are intertwined with each other, and are joined at some of the contacts. ing. That is, the fibrous organic matter is intertwined with at least a part of calcium phosphate, and further forms an organic-inorganic composite porous body formed by joining a part thereof, so that it has a continuous pore structure and has pores. Fibrous calcium phosphate is exposed inside and on the surface of the organic-inorganic composite porous body. Specifically, fibrous calcium phosphate pores in the surface and organic - because many parts are exposed to the surface of the inorganic composite porous material, is excellent in biocompatibility. Furthermore, since the fibrous calcium phosphate has hydrophilicity, it has good wettability to water and has continuous continuous air holes, so that cells and tissues in the living body can easily invade and become familiar with the living body. Therefore, the porous body of the present invention is very useful as a biomaterial. In addition, by using fibrous calcium phosphate having a high adsorbing capacity, it becomes a material that makes use of the adsorption performance of fibrous calcium phosphate and has a continuous ventilation hole with good liquid and gas permeability such as containing an adsorbing substance. It is also useful as an environmental material.

  That is, the organic-inorganic composite porous body having such a unique structure is suitable as a biomaterial, a filling material, and an environmental material.

(2) Manufacturing method of fibrous organic matter According to the manufacturing method of fibrous organic matter referred to in the present invention, the fibrous organic matter is a solvent solution obtained by dissolving an organic matter in a solvent, a water-soluble polymer, and a water-soluble polymer coagulation. It can manufacture by mixing the aqueous solution containing an agent, obtaining a liquid mixture, and then, after stirring the liquid mixture, removing the solvent component in the liquid mixture. According to such a production method, it can be produced without using a special apparatus which is simpler than a conventional production method, for example, a method produced by a spray method or a wet spinning method.

Such an unprecedented simple method for producing a fibrous organic material can be used as a raw material for producing a non-woven fabric in the form of a sheet, in addition to the raw material for producing an organic-inorganic composite porous body.

The organic material may be any organic material that can be used as an environmental material for the purpose of adsorbing pollutants, such as a dental material or bone filling material that is a biological material, a packing material such as a column, and the like. Biodegradable resins are preferred.

As the biodegradable resin , in particular, at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid and polycaprolactone, or at least one selected from the group consisting of lactic acid, glycolic acid and caprolactone And a copolymer containing the above monomer as a repeating unit. These are preferred for the reasons already described.

  As a solvent used for preparing a solvent solution obtained by dissolving an organic substance in a solvent, a solvent slightly soluble in water and having a lower volatilization temperature than water can be cited as a preferred example. . Examples of the solvent include at least one selected from the group consisting of methylene chloride, chloroform, dichloroethane, and ethyl acetate.

  The concentration of the organic substance in this solvent solution is usually below the saturation concentration.

  This aqueous solution needs to contain a water-soluble polymer. When the water-soluble polymer is contained in the aqueous solution, fibrous organic substances can be precipitated by the effect of the water-soluble polymer coagulant contained in the aqueous solution and the water-soluble polymer.

  The water-soluble polymer is not particularly limited as long as the polymer is condensed at the interface between the solvent and the aqueous solution by the water-soluble polymer coagulant coexisting in the aqueous solution, and polyvinyl alcohol is particularly preferable from the viewpoint of economy. Polyvinyl alcohol is suitable as an additive because it is inexpensive and has relatively high safety to living bodies even when it remains in the fibrous organic matter. The content of the water-soluble polymer in the aqueous solution is not particularly limited because the optimum amount varies depending on the type and molecular weight of the water-soluble polymer to be used, but is usually preferably 0.001% by mass to 10% by mass.

  The water-soluble polymer coagulant preferably contains a condensed phosphate and / or sulfate. In particular, it is preferable to use condensed sodium phosphate or sodium sulfate. Some water-soluble polymer coagulants change their effects depending on the pH in the aqueous solution, so an acid or alkali may be added as a pH adjuster to the aqueous solution to which the water-soluble polymer coagulant is added. For example, in the case of sodium sulfate, since the effect is exhibited by making it alkaline, it is preferable to add an alkali such as sodium hydroxide together with sodium sulfate.

  Examples of the condensed phosphate include sodium pyrophosphate, sodium tripolyphosphate, and sodium hexametaphosphate. The condensed phosphate prepared in the aqueous solution may be one of the condensed phosphates or two or more.

  The concentration of the condensed phosphate in the aqueous solution is usually 0.001 to 1M. If the concentration is low, there is no effect of making the organic matter into a fibrous form, and if the concentration is too high, a precipitate of condensed phosphate may be formed, which may be undesirable.

  As a mixing ratio of a solvent solution obtained by dissolving an organic substance in a solvent and an aqueous solution containing a water-soluble polymer and a water-soluble polymer coagulant, the ratio of the volume of the solvent solution to the volume of the aqueous solution (volume ratio) is: Usually, 1: 1 to 1: 500 is preferable. Although it varies depending on the type of the solvent, organic matter, etc., when the solvent solution and the aqueous solution are mixed at such a volume ratio, the organic matter is easily formed into a good fibrous form in the aqueous solution and easily precipitated.

In the method referred to by the present invention, the solvent solution and the aqueous solution are usually mixed at room temperature. But you may mix the said solvent solution and the said aqueous solution, heating and cooling as needed.

  The solvent solution and the aqueous solution may be mixed with stirring or may be mixed and then stirred. In any case, it is preferable that the solvent solution and the aqueous solution are mixed and then sufficiently stirred. When stirring, the solvent in which the organic substance is dissolved is dispersed in the aqueous solution, and in the dispersed state, only the solvent is gradually dissolved at the interface between the solvent and the aqueous solution, and the solvent having a lower volatilization temperature than water volatilizes from the water surface. As a result, the concentration of the organic substance dissolved in the solvent solution increases, and finally the organic substance becomes a fiber and precipitates in the aqueous solution. During stirring, it is carried out under normal pressure or reduced pressure, while heating or at room temperature. For the stirring, a stirring device such as a stirrer can be used, and the length of the fibrous organic material obtained can be adjusted by the stirring speed. The faster the stirring speed, the shorter the fibrous organic matter is obtained, and the slower the stirring speed, the longer the fibrous organic matter is obtained.

  After sufficiently stirring and volatilization of the solvent, the fibrous organic matter dispersed in the aqueous solution is separated by filtration, centrifugation, etc., and dried using a dryer or the like. In the case where a biodegradable resin is used for the organic substance, it may be decomposed by heating, and therefore it is preferable to perform drying under reduced pressure.

  The fibrous organic matter can be purified according to a general chemical cleaning method or purification method. For example, after the fibrous organic substance is sufficiently washed with pure water, the wet fibrous organic substance is dried to obtain a fibrous organic substance from which the water-soluble polymer and the like attached to the surface are removed.

(3) Manufacturing method of organic-inorganic composite porous body The manufacturing method of the organic-inorganic composite porous body of the present invention comprises mixing a fibrous organic substance and fibrous calcium phosphate, and at least part of the fibrous organic substance and fibrous calcium phosphate. In addition, the organic-inorganic composite porous body of the present invention can be easily manufactured, characterized in that one aspect of the entangled state is a joined state. The organic-inorganic composite porous body has a porous structure in which fibrous calcium phosphate is exposed on the pore inner surface and the porous body surface, and has high communication properties.

  In this method for producing an organic-inorganic composite porous body, the fibrous organic substance and fibrous calcium phosphate can be joined by heating under pressure as in the production method of the present invention or under normal pressure. A method in which the parts to be joined are melted and fixed to each other, that is, a welding method is particularly preferable, but a method in which the parts to be joined to each other are fixed with an organic substance serving as an adhesive can also be used. According to this welding method, bonding between fibrous organic substances also occurs.

  In addition to the heat welding method as described above, by bringing the mixture of the fibrous organic substance and fibrous calcium phosphate into a solvent capable of dissolving the fibrous organic substance so that the surface of the fibrous organic substance is dissolved, and then drying. And a method of joining the fibrous calcium phosphate and the fibrous organic substance. Even in this case, bonding between the fibrous organic substances occurs. This method of realizing the joining of the fibrous organic substance and the fibrous calcium phosphate and the joining of the fibrous organic substances by dissolving the surface of the fibrous organic substance with the solvent partially dissolves the surface of the fibrous organic substance with the solvent. Therefore, it can be said that this is a welding method using a solvent. In addition, in the welding method using a solvent, the solvent to be used may be an amount that can dissolve the surface of the fibrous organic material, and the type of solvent and the amount to be used are appropriately selected according to the type of fibrous organic material. be able to.

  According to the method for producing an organic-inorganic composite porous body according to the present invention, a fibrous organic material and fibrous calcium phosphate are mixed and thermoformed to form a surface in a pore, a surface of the organic-inorganic composite porous body, and the like. Most of the fibrous calcium phosphate contained in the organic-inorganic composite porous body exists in an exposed state, and the degree of exposure of the fibrous calcium phosphate contained in the organic-inorganic composite porous body is high, and the pores It is possible to produce the organic-inorganic composite porous body of the present invention having a pore structure with a high rate and including pores distributed in the range of 10 to 1000 μm and rich in communication.

  The mixing ratio of the fibrous organic matter and the fibrous calcium phosphate is within the ranges described above for the content ratio of the fibrous organic matter in the organic-inorganic composite porous body and the content ratio of the fibrous calcium phosphate in the organic-inorganic composite porous body. Thus, it is appropriately determined according to the use of the organic-inorganic composite porous body.

  The mixture of the fibrous organic matter and the fibrous calcium phosphate can be obtained by mixing the isolated fibrous organic matter and the isolated fibrous calcium phosphate. The method for producing the fibrous organic matter of the present invention A mixture obtained by mixing the fibrous organic material produced by the above and fibrous calcium phosphate is preferred.

  The mixing method of the fibrous organic matter and the fibrous calcium phosphate is not particularly limited. For example, the fibrous organic matter and the fibrous calcium phosphate are dispersed in pure water, the resulting dispersion is filtered, and the solid content separated by filtration is filtered. The mixture can be obtained by drying. As a dispersion method at this time, a stirrer, ultrasonic treatment, or the like can be employed. The composition ratio between the fibrous calcium phosphate and the fibrous organic substance is improved in biocompatibility as the amount of the fibrous calcium phosphate increases. However, the contact point between the fibrous organic substance and the fibrous calcium phosphate or other fibrous organic substance is increased. The strength decreases because it decreases. Conversely, as the amount of fibrous calcium phosphate decreases, the strength of the organic-inorganic composite porous body increases, but the biocompatibility decreases. Therefore, it is necessary to adjust the composition ratio according to the place in the living body to be used.

  Furthermore, the porosity and the pore diameter may be controlled using a pore-forming agent such as a foaming agent and soluble particles during the preparation of the organic-inorganic composite porous body. In particular, it is preferable to use soluble particles because of the ease of operation. Particles that are soluble in water, that is, soluble particles are added to a mixture of fibrous organic matter and fibrous calcium phosphate, heat-molded, and then immersed in a solvent such as water to dissolve only soluble particles. And a method of forming pores. Since the organic-inorganic composite porous body obtained in this way has a mesh structure formed with fibrous calcium phosphate and fibrous organic matter in the skeleton between pores formed with the pore-forming agent, It becomes a material with excellent communication between pores. In addition, since the pore diameter formed by the pore-forming agent and the pore diameter of the mesh structure can be controlled, the pore diameter can be controlled according to the application. The pore size formed by the pore-forming agent is adjusted by adjusting the particle size of the soluble particles. The pore size of the mesh structure is the shape and size of the fibrous calcium phosphate and the fibrous organic matter, and further, the porous body is molded. It can be controlled by the pressure of time.

  Examples of the solvent used in the present invention include a solvent that does not substantially dissolve the fibrous organic matter or fibrous calcium phosphate constituting the organic-inorganic composite porous body and can dissolve soluble particles. Examples of the solvent include water, ethanol, methanol and the like, and water is particularly preferable. Suitable soluble particles include particles that are soluble in the solvent, particularly water. Suitable examples of the soluble particles include water-soluble polysaccharides and / or water-soluble inorganic salts. Here, examples of the water-soluble polysaccharide include sucrose, dextran, and dextran sulfate. Examples of water-soluble inorganic salts include alkali metal halides such as sodium chloride and potassium chloride, and alkaline earth metal halides such as calcium chloride.

  If the average particle size of the soluble particles is too small, it will not play a role as a pore-forming agent, and if it is too large, it will be difficult to disperse the pores uniformly, so the average particle size is in the range of 10 μm to 2 mm. More preferably. Further, the amount of the soluble particles added is not particularly limited because it is necessary to set an optimum amount depending on the porosity of the mesh structure as a skeleton, but the final porosity of the organic-inorganic composite porous body is 30% or more. Such an amount is preferred.

  In the present invention, the mixture of fibrous organic matter and fibrous calcium phosphate is then heat molded.

  The heating temperature varies depending on the type of fibrous organic matter, but generally speaking, it is not less than the softening temperature of the fibrous organic matter and not more than the decomposition temperature, and is usually 50 to 300 ° C, particularly preferably 100 to 250 ° C.

  When heated in such a heating temperature range, the contact portion is joined by melting of the fibrous organic matter at the contact portion between the fibrous organic matter or between the fibrous organic matter and the fibrous calcium phosphate. -An inorganic composite porous body can be produced. In this respect, the method of the present invention can produce an organic-inorganic composite porous body at a low temperature compared to the temperature at which ceramics such as fibrous calcium phosphate are fired, so that the added fibrous calcium phosphate can be easily decomposed. This is advantageous in terms of cost.

  When the heating temperature is low, the fibrous organic materials or between the fibrous organic material and the fibrous calcium phosphate may not be joined by melting, and therefore the strength of the organic-inorganic composite porous body is extremely reduced. The handling property may be deteriorated, and if it is excessively high, the whole fibrous organic substance may be melted, and the pores may not be maintained. Therefore, the heating temperature can be determined according to the type and molecular weight of the fibrous organic matter. The heating may be performed simultaneously with the molding, may be performed after the molding, or may be pressurized during the molding.

  According to the use of the organic-inorganic composite porous body, the mold is filled with a mixture of a fibrous organic substance and fibrous calcium phosphate in a desired mold, heated to the heating temperature, and further pressurized in some cases, Done.

  The fibrous calcium phosphate used in the present invention includes hydroxyapatite, carbonate apatite, fluorapatite, calcium hydrogen phosphate, calcium hydrogen phosphate hydrate, α-type tricalcium phosphate, β-type calcium phosphate, and tetraphosphate phosphate. There may be mentioned at least one of calcium, monocalcium phosphate, and monobasic calcium phosphate hydrate. Since these fibrous calcium phosphates differ in solubility depending on each compound, for example, when used as a biomaterial, these fibrous calcium phosphates can be selected and used from among these in order to adjust the absorption substitution rate.

  The form of fibrous calcium phosphate is usually fibrous. Among these, apatite whiskers are preferable as the fibrous calcium phosphate. By being fibrous, the entanglement with the fibrous organic matter becomes good, and an organic-inorganic composite porous body having continuous air holes can be easily produced. In addition, the number of joints between the fibrous calcium phosphate and the fibrous organic material is increased, and the organic-inorganic composite is formed by the entanglement between the fibrous calcium phosphate, the entanglement between the fibrous organic materials, and the entanglement between the fibrous calcium phosphate and the fibrous organic material. It becomes easy to support fibrous calcium phosphate in the porous body, and the content of fibrous calcium phosphate can be increased. Furthermore, by increasing the content of fibrous calcium phosphate, an organic-inorganic composite porous body having an excellent pore structure can be obtained without impeding communication.

  The organic-inorganic composite porous body of the present invention and the organic-inorganic composite porous body obtained by the production method thereof may be used as a carrier for a drug delivery system by supporting a drug such as an osteogenic factor, It may be used as a carrier for regenerative medicine that is used after carrying or cultivating etc. Moreover, the organic-inorganic composite porous body of the present invention can be used in the form of a granule, a block or the like according to the application site.

Hereinafter, the present invention will be described more specifically with reference to Examples , Comparative Examples, and Reference Examples . In addition, this invention is not limited to the content of the Example.

( Reference Example 1: Manufacturing method of fibrous organic matter)
A solvent solution is prepared by dissolving 1 g of polylactic acid having an average molecular weight of 160,000 in 15 mL of methylene chloride. This solvent solution is prepared by adding sodium tripolyphosphate having a concentration of 0.1M and an average molecular weight of 22000 having a concentration of 0.01% by mass. Was added to 500 mL of an aqueous solution containing polyvinyl alcohol. While stirring this mixed solution for 24 hours, methylene chloride dispersed in the mixed solution was volatilized to remove methylene chloride, and polylactic acid dissolved in methylene chloride was precipitated in an aqueous solution. Thereafter, the aqueous solution was filtered, washed with pure water, and dried in a vacuum desiccator. The obtained polylactic acid was in the form of fibers having a length of about 100 μm to 2 mm.

( Reference Example 2: Manufacturing method of fibrous organic matter)
A solvent solution is prepared by dissolving 1 g of polylactic acid having an average molecular weight of 160,000 in 15 mL of methylene chloride, and this solvent solution is made of sodium tripolyphosphate having a concentration of 0.1M and an average molecular weight of 1500 having a concentration of 0.01% by mass. Was added to 500 mL of an aqueous solution containing polyvinyl alcohol. While stirring this mixed solution for 24 hours, methylene chloride dispersed in the mixed solution was volatilized to remove methylene chloride, and polylactic acid dissolved in methylene chloride was precipitated in an aqueous solution. Then, this aqueous solution was filtered, the solid content separated by filtration was washed with pure water, and the solid content after washing was dried in a vacuum desiccator. The fibrous polylactic acid thus obtained had an average length of about 1 mm.

( Reference Example 3: Manufacturing method of fibrous organic matter)
A solvent solution is prepared by dissolving 1 g of polylactic acid having an average molecular weight of 160,000 in 15 mL of methylene chloride. The solvent solution is prepared by adding sodium sulfate having a concentration of 0.2M and an average molecular weight of 22000 having a concentration of 0.01% by mass. The solution was added to 500 mL of an aqueous solution containing polyvinyl alcohol and sodium hydroxide as a pH adjuster. The pH of the aqueous solution at this time was 9. While stirring this mixed solution for 24 hours, methylene chloride dispersed in the mixed solution was volatilized to remove methylene chloride, and polylactic acid dissolved in methylene chloride was precipitated in an aqueous solution. Then, this aqueous solution was filtered, the solid content separated by filtration was washed with pure water, and the solid content after washing was dried in a vacuum desiccator. The fibrous polylactic acid thus obtained had an average length of about 0.5 mm.

( Reference Example 4 )
A solvent solution is prepared by dissolving 1 g of polylactic acid having an average molecular weight of 160,000 in 15 mL of methylene chloride, and the solvent solution is added to 500 mL of an aqueous solution containing polyvinyl alcohol having an average molecular weight of 22000 at a concentration of 0.01% by mass. Added. While stirring this mixed solution for 24 hours, methylene chloride dispersed in the mixed solution was volatilized to remove methylene chloride, and polylactic acid dissolved in methylene chloride was precipitated in an aqueous solution. Thereafter, this aqueous solution was filtered, and the solid content separated by filtration was washed with pure water and dried in a vacuum desiccator after washing. The polylactic acid thus obtained was in the form of a spherical or irregular mixture, and fibrous polylactic acid was not obtained. The reason is that no water-soluble polymer coagulant was used.

( Reference Example 5 )
A solvent solution was prepared by dissolving 1 g of polylactic acid having an average molecular weight of 160,000 in 15 mL of methylene chloride, and this solvent solution was added to 500 mL of an aqueous solution containing sodium tripolyphosphate to a concentration of 0.1M. . While stirring this mixed solution for 24 hours, methylene chloride dispersed in the mixed solution was volatilized to remove methylene chloride, and polylactic acid dissolved in methylene chloride was precipitated in an aqueous solution. Thereafter, this aqueous solution was filtered, the solid content separated by filtration was washed with pure water, and the solid content after washing was dried in a vacuum desiccator. The shape of the obtained polylactic acid was indefinite, and fibrous polylactic acid was not obtained. The reason is that no water-soluble polymer was used.

(Examples 1-5 )
In Examples 1 to 5 , the fibrous polylactic acid synthesized in Reference Example 1 was used. Hydroxyapatite whiskers used in Examples 1 to 5 were prepared as follows. That is, a dispersion having a pH of 2.4 is prepared by adding nitric acid to a gel solution containing 0.025M sodium tripolyphosphate, 0.125M calcium nitrate, and 30% by volume of propanol. Was treated in an airtight container at 140 ° C. for 24 hours, and then the dispersion was filtered, and the solid matter separated by filtration was dried. The pH of the filtrate was measured as the pH after the heat treatment, and the value was 4.1. The average length of this whisker was about 60 μm. These fibrous polylactic acid and hydroxyapatite whiskers are weighed in predetermined amounts, stirred in ethanol, filtered, and the solid matter separated by filtration is dried under reduced pressure, thus obtaining a mixture of fibrous organic matter and fibrous calcium phosphate. It was. This mixture was filled in a mold having a diameter of 6 mm and a height of 5 mm, heat-treated at 170 ° C. to 180 ° C., and then cooled to obtain an organic-inorganic composite porous body.

(Examples 6 to 8 )
In Examples 6 to 8 , the fibrous polylactic acid synthesized in Reference Example 1 was used. The soluble particles used in Examples 6-8 are 355-850 μm saccharose obtained by sieving. Further, the hydroxyapatite whiskers used in Examples 6 to 8 were obtained by the same method as in Examples 1 to 5 . Weigh these in a predetermined amount, stir the dispersion obtained by adding them to ethanol, filter the dispersion, and dry the filtered solids under reduced pressure, thus soluble in fibrous organic matter, fibrous calcium phosphate and A mixture with the particles was obtained. A mold having an inner volume of 6 mm in diameter and 8 mm in height is filled with the mixture, uniaxially pressed at a pressure of 100 Mpa, heat-treated at 170 to 180 ° C., and then the pressure-molded body taken out from the mold is obtained. By soaking in pure water, the soluble particles in the pressure-molded body were dissolved. The cylindrical body taken out from the pure water was dried under reduced pressure to obtain a cylindrical organic-inorganic composite porous body having a diameter of 6 mm and a height of 8 mm.

  Table 1 shows the composition ratio of hydroxyapatite whisker and polylactic acid, the porosity of the obtained organic-inorganic composite porous material, the volume ratio of pores of 10 μm or more measured with a mercury porosimeter, and the water penetration time. Indicated. The method for evaluating the water penetration time is to drop one drop (10 μL) of pure water on the surface of the organic-inorganic composite porous body with a micropipette and measure the time until the water drops completely penetrate into the organic-inorganic composite porous body. It is a method of measuring.

Moreover, as a result of observing the fracture surface of the organic-inorganic composite porous body of Examples 1-8 with SEM, the porous body of Examples 1-8 showed that fibrous polylactic acid and hydroxyapatite whiskers were mutually observed by SEM. It was entangled and welded at a part of the contacts, and it was confirmed that the organic-inorganic composite porous body was formed by intertwining fibrous organic matter and fibrous calcium phosphate and joining at least a part thereof. It was also found that fine hydroxyapatite whiskers were welded to the surface of fibrous polylactic acid.
In addition, the SEM photograph of the organic-inorganic composite porous body obtained in Examples 2 to 5 is shown in FIGS. Moreover, the external appearance photograph of the organic-inorganic composite porous body obtained in Example 8 as a typical example of the organic-inorganic composite porous body obtained in Examples 6 to 8 is shown in FIG. It can be seen that large pores are formed by the addition of soluble particles. In the organic-inorganic composite porous material shown in FIG. 7, in order to clarify the contrast between the pores and the surface of the organic-inorganic composite porous material, and to make the pores easy to observe, the surface of the organic-inorganic composite porous material is carbon. Vapor deposition was performed.

(Comparative Example 1 )
The low crystalline apatite used in Comparative Example 1 was prepared by wet milling calcium carbonate and calcium hydrogen phosphate, filtering the resulting mixture, drying the solid matter separated by filtration, and drying the dried product to 150 μm. Obtained by sieving. As a result of observing this low crystalline apatite with SEM, it was found to be aggregated particles having an average particle diameter of 8 μm. 0.1 g of this low crystalline apatite is added to a polylactic acid solution in which 1 g of polylactic acid having an average molecular weight of 160,000 is dissolved in 10 mL of methylene chloride, and a suspension solvent solution is obtained by dispersing the low crystalline apatite in the polylactic acid solution. It was. This suspension solvent solution was added to 500 mL of an aqueous solution containing polyvinyl alcohol having an average molecular weight of 22000 so as to have a concentration of 0.02% by mass and stirred for 24 hours to obtain an aqueous solution. The aqueous solution was filtered, the solid content separated by filtration was washed with pure water, and the washed solid content was dried in a vacuum desiccator. By this method, spherical polylactic acid containing low crystalline apatite was obtained. The obtained spherical polylactic acid had an average diameter of 600 μm. The spherical polylactic acid is filled into a disk-shaped mold having a diameter of 7 mm and a height of 5 mm, and the filled mold is placed in a dryer at a temperature of 170 ° C., and an organic-inorganic containing 10% by mass of apatite. A composite porous body was produced. In addition, the SEM photograph of the organic-inorganic composite porous body obtained in Comparative Example 1 is shown in FIG. 6 as a representative example. The obtained organic-inorganic composite porous body was evaluated for its water permeability. This evaluation was performed by dropping pure water on the surface of the porous body in the same manner as in the Examples, and comparing the time until the water drops completely penetrate into the porous body. As a result, even after 30 minutes from the dropping, water droplets did not completely penetrate into the organic-inorganic composite porous body. This is because the organic-inorganic composite porous body according to Comparative Example 1 is formed of calcium phosphate and spherical polylactic acid, and the proportion of calcium phosphate exposed on the surface of the pores is small. It is estimated that water droplets did not completely penetrate into the organic-inorganic composite porous body.
(Comparative Example 2 )
In Comparative Example 2 , the low crystalline apatite used in Comparative Example 1 and the fibrous polylactic acid synthesized in Reference Example 1 were used. These fibrous polylactic acid and low crystalline apatite are weighed in a predetermined amount, stirred in ethanol, filtered, and the solid matter separated by filtration is dried under reduced pressure, thus obtaining a mixture of fibrous organic matter and fibrous calcium phosphate. It was. This mixture was filled in a mold having a diameter of 6 mm and a height of 5 mm, heat-treated at 170 ° C. to 180 ° C., and then cooled to obtain an organic-inorganic composite porous body.

Comparing Reference Examples 1 to 3 and Reference Examples 4 and 5 , in order to produce a fibrous organic material, condensed phosphate and sodium sulfate which are water-soluble polymer coagulants and polyvinyl alcohol which is a water-soluble polymer and It was found that the fibrous organic matter can be easily produced without requiring a special apparatus by the operations of Reference Examples 1 to 3.

According to Examples 1 to 5 , the organic of the present invention is formed by mixing fibrous calcium phosphate and fibrous organic matter and then heat-molding so that the fibrous organic matter and fibrous calcium phosphate are intertwined, and at least a part thereof is joined. -It has been confirmed that an inorganic composite porous body can be produced. Moreover, since the shape could be made into the same block shape as the shape of a type | mold, it turned out that the porous body of various shapes can be manufactured by selecting the shape of a type | mold.

According to Examples 6 to 8 , fibrous organic phosphate and fibrous organic matter are mixed with fibrous organic matter and sucrose as soluble particles, and after thermoforming, immersed in pure water and dried, the fibrous organic matter and fibrous matter are also obtained. It was confirmed that calcium phosphate was entangled and at least a part of the calcium phosphate was joined to produce the organic-inorganic composite porous body of the present invention.

The organic-inorganic composite porous body in Examples 1 to 5 includes fibrous calcium phosphate and fibrous organic matter, and is formed by joining the fibrous organic matter and at least a part of the apatite whisker that is fibrous calcium phosphate. The structure was a structure including a volume ratio of pore diameters of 10 μm or more containing 80% or more, and was a porous structure rich in communication. On the other hand, when low crystalline apatite, which is aggregated particles, was added as calcium phosphate as in Comparative Example 2 , it was found that the volume ratio of the pore diameter of 10 μm or more was 50% or less. Even when the same amount of apatite as in Comparative Example 2 was added, by using an apatite whisker as fibrous calcium phosphate, the volume ratio of the pore diameter of 10 μm or more could be increased to 80% or more as in Example 2. Thus, it was found that it is necessary to use fibrous calcium phosphate in order to make the pore structure rich in communication. Furthermore, when low crystalline apatite, which is an aggregated particle, is compounded, there is no entanglement with fibrous polylactic acid. There was a problem of falling off. However, when an apatite whisker is used, the apatite whisker is difficult to fall because it is compounded by entanglement with fibrous polylactic acid.

Furthermore, also in Examples 6 to 8 , the volume ratio of pores of 10 μm or more can be similarly set to 60% or more, and the pore structure was observed with an electron microscope or an optical microscope. As a result, large pores of 100 μm or more were obtained. It was found that the skeleton portion had a mesh structure. The pore diameter of this mesh structure is found to be 1 to several tens of μm from the results of measurement with a mercury porosimeter, providing a scaffold for promoting cell proliferation and tissue growth, and having good nutrient permeability It was found that it can be a useful material as a biomaterial.

Moreover, the organic-inorganic composite porous bodies in Examples 1 to 8 all have a high porosity of 60 to 90%. Therefore, from the results of these examples, when the organic-inorganic composite porous body according to the present invention is used as a medical material, it becomes a material in which biological tissue or cells easily enter the material and is easily adapted to the living body. When used as a material or the like, it is useful because it has good gas and liquid permeability.

Furthermore, as a result of evaluating the water permeability of the organic-inorganic composite porous body of Examples 1-8, the organic-inorganic composite porous body of Examples 1-8 soaked water at the moment when a water droplet was dropped. The permeability of the organic-inorganic composite porous bodies of Examples 1 to 8 was found to be very good. This result indicates that a large amount of hydrophilic fibrous calcium phosphate is exposed on the surface, indicating that the organic-inorganic composite porous body effectively exhibits the characteristics of the fibrous calcium phosphate. In particular, when Comparative Example 1 and Example 1 are compared, despite the same amount of hydroxide apatite, the water permeation time differs greatly. Since the porous body is formed by using fibrous organic matter and entangled with fibrous calcium phosphate, it can be said that the organic-inorganic composite porous body effectively utilizes the characteristics of fibrous calcium phosphate. Therefore, the organic-inorganic composite porous body according to the present invention can effectively utilize the biological activity of fibrous calcium phosphate when used as a medical material, and when used as an environmental material and a filling material, fibrous calcium phosphate, particularly apatite. This is very useful.

* HAp: Hydroxyapatite (hydroxyapatite)

1 is a pore size distribution diagram measured with the mercury porosimeter of Example 3. FIG. FIG. 2 is an SEM photograph of the organic-inorganic composite porous material obtained in Example 2 . FIG. 3 is an SEM photograph of the organic-inorganic composite porous material obtained in Example 3 . FIG. 4 is an SEM photograph of the organic-inorganic composite porous material obtained in Example 4 . FIG. 5 is a SEM photograph of the organic-inorganic composite porous material obtained in Example 5 . FIG. 6 is an SEM photograph of the organic-inorganic composite porous body obtained in Comparative Example 1 . FIG. 7 is an appearance photograph of the organic-inorganic composite porous material obtained in Example 8 .

Claims (22)

  An organic-inorganic composite porous body comprising a fibrous calcium phosphate and a fibrous organic substance, wherein the fibrous organic substance and at least a part of the fibrous calcium phosphate are intertwined.   2. The organic-inorganic composite porous body according to claim 1, wherein at least a part of at least a part of the entanglement between the fibrous organic substance and the fibrous calcium phosphate is joined.   The organic-inorganic composite porous body according to claim 1 or 2, wherein the porosity is at least 30%.   The organic-inorganic composite porous body according to any one of claims 1 to 3, wherein the fibrous organic substance is a biodegradable resin.   The biodegradable resin is at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid, and polycaprolactone, and / or at least one selected from the group consisting of lactic acid, glycolic acid, and caprolactone. The organic-inorganic composite porous body according to claim 4, comprising a copolymer obtained using a monomer.   The organic-inorganic composite porous body according to any one of claims 1 to 5, wherein the fibrous calcium phosphate is an apatite whisker.   A method for producing an organic-inorganic composite porous body, comprising mixing a fibrous organic substance and fibrous calcium phosphate, and bonding the fibrous organic substance and at least a part of the fibrous calcium phosphate by welding.   The method for producing an organic-inorganic composite porous body according to claim 7, wherein the welding is achieved by melting a fibrous organic substance.   The method for producing an organic-inorganic composite porous body according to claim 7 or 8, wherein the fibrous calcium phosphate is an apatite whisker.   The method for producing an organic-inorganic composite porous body according to any one of claims 7 to 9, wherein the fibrous organic substance is a biodegradable resin.   The biodegradable resin is at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid, and polycaprolactone, and / or at least one selected from the group consisting of lactic acid, glycolic acid, and caprolactone. The method for producing an organic-inorganic composite porous body according to claim 10, comprising a copolymer obtained using a monomer.   The fibrous organic matter is obtained by mixing a solvent solution obtained by dissolving an organic matter in a solvent, a water-soluble polymer and a water-soluble polymer coagulant to obtain a mixture, and stirring the mixture. It is a fibrous organic substance obtained by the manufacturing method of the fibrous organic substance characterized by including the process of removing the solvent component in the said liquid mixture, The said any one of Claims 7-11 characterized by the above-mentioned. The manufacturing method of the organic-inorganic composite porous body described in 1.   The method for producing an organic-inorganic composite porous body according to claim 12, wherein the water-soluble polymer is polyvinyl alcohol.   The method for producing an organic-inorganic composite porous body according to claim 12 or 13, wherein the organic substance is a biodegradable resin.   The biodegradable resin is at least one polymer selected from the group consisting of polylactic acid, polyglycolic acid, and polycaprolactone, and / or at least one selected from the group consisting of lactic acid, glycolic acid, and caprolactone. The method for producing an organic-inorganic composite porous body according to claim 14, comprising a copolymer obtained by using a monomer.   The method for producing an organic-inorganic composite porous body according to any one of claims 12 to 15, wherein the water-soluble polymer coagulant contains a condensed phosphate and / or a sulfate.   The organic-inorganic composite porous body according to claim 16, wherein the condensed phosphate contains at least one selected from the group consisting of sodium pyrophosphate, sodium tripolyphosphate, and sodium hexametaphosphate. Method.   The organic-inorganic composite porous body according to any one of claims 12 to 17, wherein the solvent is at least one selected from the group consisting of methylene chloride, chloroform, dichloroethane, and ethyl acetate. Manufacturing method.   A dispersion step of obtaining a dispersion by dispersing a calcium phosphate gel compound in which the apatite whisker generates orthophosphoric acid and protons at 80 to 250 ° C. in a solvent containing at least one of water and a hydrophilic organic solvent; In which the dispersion is heated to 80 to 250 ° C., the pH of the dispersion before heating is 9 or less, and the pH of the dispersion after heating is 3.9 to 9. The method for producing an organic-inorganic composite porous body according to any one of claims 9 to 18, wherein the apatite whisker is obtained.   The method for producing an organic-inorganic composite porous body according to any one of claims 7 to 19, wherein soluble particles are added to the mixture of the fibrous organic material and the fibrous calcium phosphate.   21. The method for producing an organic-inorganic composite porous body according to claim 20, wherein the soluble particles are removed with a solvent after at least a part of the fibrous organic material and the fibrous calcium phosphate are joined by welding.   The method for producing an organic-inorganic composite porous body according to claim 20 or 21, wherein the soluble particles are water-soluble polysaccharides and / or water-soluble inorganic salts.

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