JP2002210002A - Composition for restoring biological tissue - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a slurry, a paste or a putty-like composition having excellent biocompatibility mainly used as a bone filler or an artificial joint fixing cement and a medical implant material obtained by curing the composition in an aqueous solution. SOLUTION: The material for developing high organic affinity, bioactivity or biological absorbability as the composition cured by contacting with the aqueous solution as the slurry, paste or putty-like composition is prepared by dissolving a biocompatible organic polymer soluble in an organic solvent and insoluble in water in the organic solvent soluble in water and mixing the solution with the biocompatible filler. The composition for restoring a biological tissue comprises the biocompatible organic polymer compound which is a cellulose acetate, ethyl cellulose, polylactide or copolylactide.glycolide or a mixture of two or more of them, and the biocompatible filler which is a hydroxy apatite, calcium phosphate, calcium silicate glass, calcium phosphate glass or the like or bioactive glass or a mixture of two or more of them.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for repairing a living tissue and a material for repairing a living tissue having excellent biocompatibility used in the fields of dentistry, orthopedics and plastic surgery. More specifically, the present invention relates to a composition for repairing a living tissue, which is obtained by dissolving an organic polymer compound soluble in an organic solvent and insoluble in water in an organic solvent compatible with water and adding a biocompatible filler thereto. Since the composition hardens upon contact with an aqueous solution, it can be used as a bone cement or an implant material made therefrom. The invention also relates to such an implant material.

[0002]

2. Description of the Related Art When a living tissue is repaired using an artificial material such as an artificial hip joint, an artificial knee joint, or an osteosynthesis material, it can be fixed to an arbitrary shape after mixing in an operating room for several minutes and then solidified. Hardening bone cement and bone filler are used. The most widespread cement of this type is
About 50-75% by weight of finely divided polymer of acrylic and / or methacrylic acid ester and optionally other additives such as polymerization catalyst, X-ray contrast agent, filler and dye
About 25 to 50% by weight of a liquid component consisting of a solid component and other additives such as an acrylic and / or methacrylic acid ester monomer and a polymerization accelerator and a stabilizer (hereinafter abbreviated as PMMA-based bone cement) . For example, a powder containing polymethyl methacrylate (PMMA) as a main component and mixed with a contrast agent, a catalyst or a reaction inducer, and if necessary, an antibiotic, is mixed with a methyl methacrylate monomer (MM).
Bone cement that is polymerized and hardened by mixing with a liquid containing A) as a main component. However, the bone cement is a material with low biocompatibility that is encapsulated by a relatively thick fibrous cap due to a foreign body reaction, and the connection with the tissue is based only on mechanical engagement. For this reason, there is a case where displacement or loosening occurs during long-term implantation, and reoperation is required.

On the other hand, bioactive ceramics such as bioactive glass and hydroxyapatite and materials containing them are
It is known to integrate with bone tissue, such as by conducting bone tissue. Among these, bioactive glass has the property of forming an apatite layer on its surface in a simulated body fluid containing calcium and phosphate ions or in a living body, and it can bind to bone and soft tissue through such apatite layer. It is suitable for implant materials that require integration with living tissue because it is integrated with living tissue [C. Ohtsuki et al.
Journal of the Cer
amic Society of Japan) 103 [5], 449-454 (1995).]
Therefore, a method of mixing bioactive ceramic powder with osteoassinity into PMMA-based bone cement [W. Henning,
BA Blencke, H. Bromer and KK Deutscher, "I
nvestigation with BioactivatedPolymethylmethacryla
tes ", Journal of Biomedical Materials Research,
13, 89-99 (1979)]. However, in this method, a large amount of bioactive ceramic powder needs to be introduced into the PMMA-based bone cement in order to exhibit bioactivity, and therefore, there is a problem that the mechanical properties of the cement are impaired. There is also a method of interposing hydroxyapatite granules between PMMA-based bone cement and bone [Takao Yamamuro, Hiroyasu Onishi, "Material Manual for Orthopedic Surgeons", Kanehara Shuppan Co., Ltd. (1992) pp78-79] However, there is a problem that the simplicity of the operation is reduced.

[0004] Bone cements consisting solely of bioactive ceramics have also been proposed. α-tricalcium phosphate (α-TCP)
And acid mixed with cement [JP-A-2000-295] and a cement mixed with bioactive glass and ammonium phosphate aqueous solution [T.
Kokubo, S. Yoshihara, N. Nishimura, T. Yamamur
o, T. Nakamura, "Bioactive Bone Cement Based onC
aO-SiO ₂ -P ₂ O ₅ Glass ", Journal of American Ceramic
Society, 74, 1739-1741 (1991).] Is a typical example. However, in these cements, the mechanical properties after solidification become brittle, and the mechanical strength, toughness,
There is a problem that mechanical properties after curing are insufficient in terms of flexibility and the like.

[0005] In addition, the conventional bone cement and bone filling paste require mixing operation in an operating room because the powder and liquid are mixed immediately before use, which is inconvenient. Therefore, there is a need for a material that can be supplied in the form of a paste or putty that has already been mixed, that solidifies after implantation, and that exhibits high biocompatibility and / or bioactivity after curing.

[0006]

DISCLOSURE OF THE INVENTION The present invention is provided as a moldable composition such as a slurry, paste or putty, which can be molded in an operating room, and can be used in an aqueous medium.
(Including bodily fluids), solidification and curing progresses, and after curing, a high biocompatibility and / or bioactivity is exhibited. In particular, it is an object of the present invention to develop a material to be used as a cement for fixing a material for filling a living tissue and an implant material such as an artificial hip joint. FIG.
Fig. 1 schematically shows an example of the usage pattern.

[0007]

Means for Solving the Problems As a result of intensive studies on solving the above problems, the present inventors have found that a biocompatible organic polymer that is soluble in an organic solvent and insoluble in water is converted into an organic solvent compatible with water. And a solution prepared by mixing the solution with a biocompatible filler was prepared, and it was confirmed that this preparation solidified from the surface upon contact with an aqueous medium, gradually lost fluidity, and solidified and hardened. FIG. 2 shows a conceptual diagram of the curing mechanism. That is, when the composition in a moldable state such as a slurry, paste, or putty is in contact with a bodily fluid (water), the solvent is removed from the bodily fluid.
It is immersed in (water), and the organic polymer is precipitated from the surface and curing starts, and the curing proceeds to the inside as time passes. The solidified product after curing becomes a composite composed of a biocompatible filler and a biocompatible organic polymer compound. Therefore, the cement after hardening exhibits bone tissue bonding properties in the same manner as a cement in which bioactive ceramics are composited.

[0008] That is, the present invention is intended for use in repairing living tissue, in which a biocompatible organic polymer compound soluble in an organic solvent and insoluble in water is dissolved in an organic solvent compatible with water, and the solution is dissolved. A composition, which can be in the form of a slurry, paste or putty, mixed with a biocompatible filler,
It is characterized in that it is cured by bringing it into contact with an aqueous medium, for example, an aqueous solution or body fluid. FIG. 3 shows an outline of the procedure for producing the composition of the present invention.

Here, the biocompatible organic polymer compound used as a starting material is an organic polymer compound that is soluble in an organic solvent that is compatible with water and has low irritation to the living body. And those having biocompatibility are preferred. Further, any of natural and synthetic organic polymer compounds may be used. Furthermore, it may be a bioabsorbable polymer,
When this is used, it becomes possible to prepare a composition or the like that is absorbed in a short time in a living body. Preferably, cellulose acetate, ethyl cellulose, polylactide, copolylactide glycolide and the like are used. In addition, 2 of these polymer compounds
Mixtures of more than one species may be used.

As the solvent for dissolving the organic polymer, any solvent may be used as long as it dissolves the biocompatible organic polymer compound and is compatible with water. It is preferable that the irritation to the living tissue is small. Particularly, alcohols such as ethanol, propanol and butanol, and ester solvents such as ethyl acetate, ethyl lactate and triethyl phosphate are suitable. Further, a mixture of these solvents may be used.

On the other hand, biocompatible fillers are biocompatible,
Any filler can be used as long as it has bioactivity or bioabsorbability. For example, the filler may be in any form such as a powder, a particle, or a fiber. Further, the filler is not limited to crystalline material, and an amorphous material may be used. Particularly, biocompatible or bioactive ceramics are preferable. Examples include hydroxyapatite, tricalcium phosphate, tetracalcium phosphate, calcium phosphate, calcium carbonate, calcium silicate, calcium hydroxide, calcium oxide, calcium-containing glass, calcium silicate glass, calcium phosphate glass, and bioactive glass. . In addition, a filler that undergoes a chemical reaction in a living body and exhibits bioactivity or bioabsorbability may be used. A mixture obtained by combining some of them may be used. The surface of the filler may be treated with a coupling agent or the like before use. As a coupling agent, for example, vinyltrimethoxysilane, vinyltriethoxysilane, N- (2-aminoethyl) 3-aminopropylmethyldimethoxysilane, N- (2-aminoethyl)
3-aminopropyltrimethoxysilane, 3-aminopropyltriethoxysilane, 3-aminopropyltrimethoxysilane, 3-glycidoxypropyltrimethoxysilane, 3-glycidoxypropylmethyldimethoxysilane, 2- (3,4 -Epoxycyclohexyl) ethyltrimethoxysilane, 3-chloropropylmethyldimethoxysilane, 3-chloropropyltrimethoxysilane, 3-methacryloxypropyltrimethoxysilane, 3-mercaptopropyltrimethoxysilane, N- (1,3-dimethyl (Butylidene) -3- (triethoxysilyl) -1-propanamine, N- [2- (vinylbenzylamino) ethyl] -3-aminopropyltrimethoxysilane hydrochloride, N, N'-bis
Silane coupling agents such as [3- (trimethoxysilyl) propyl] ethylenediamine are included. The size of the filler can be arbitrarily used as long as a slurry, paste or putty-like composition can be obtained. When the filler is in the form of powder or particles, the size is preferably about 500 μm or less, and mixed powders having different particle diameters may be used. When the filler is in a fibrous form, it is preferable that the fiber has a staple or filament shape with a diameter of 0.1 μm to 500 μm.

In preparing the compositions of the present invention, a biocompatible filler and, optionally, a finely divided polymer, an X-ray contrast agent,
A mixture of fillers and other additives such as dyes is used as the solid component. Next, an organic polymer soluble in a predetermined organic solvent is dissolved or swelled in the organic solvent. At this time, other additives such as a stabilizer are appropriately added to make a liquid component. The amount of the polymer to be dissolved is approximately 10 g to 50 g per 100 mL of the solvent.
g. However, this range varies depending on the type of the organic polymer and the organic solvent. The composition of the present invention in which the solid component and the liquid component are mixed, comprises about 25 to 85% by weight of the solid component and about 1%.
Consists of 5 to 75% by weight of liquid component. Above all, about 50
Materials composed of 8080% by weight of the solid component and about 20-50% by weight of the liquid component have a high compressive strength.

The strength can be improved by mixing a ceramic component such as alumina, silica, zirconia, titania or carbon, or an organic polymer such as nylon or polyester with a solid component of the composition of the present invention as a reinforcing agent. These reinforcing agents may be used as a mixture of two or more kinds.
The reinforcing agent may be in the form of a powder, a particle, a fiber, a film, a sheet, or any other shape suitable for the function as the reinforcing agent.

Further, an agent which enhances physiological activity, such as an antibiotic, an anticancer agent, or a bone morphogenetic agent, may be mixed with the solid component or the liquid component.

The cured product of the composition of the present invention can also be used as an implant material exhibiting high biocompatibility or bioactivity. In this case, the implant material may have any shape such as a column, a plate, a block, a sheet, a fiber, and a pellet. Further, it may be in the form of a product such as an artificial joint member, a bone replacement material, an artificial vertebral body, an artificial intervertebral disc, a bone plate, a bone screw, an artificial face prosthesis material, and an artificial breast. Further, it can also be used by coating it with a filler such as metal or ceramics.

The resulting composition loses its surface fluidity in an aqueous medium such as an aqueous solution or body fluid within tens of minutes,
Solidifies in a few hours to 7 days. When the solid component of the composition is a bioactive ceramic, binding to bone tissue is achieved in the body. If the polymer or the biocompatible filler is a material that can be decomposed in a living body, it is gradually decomposed and absorbed, and is integrated with the living tissue.

According to the present invention, it has both simple moldability and tissue affinity, which can be used as a cement for fixing an artificial joint, a living tissue repair material for filling a bone defect and a soft tissue replacement material as a cement paste moldable in an operating room. It is possible to obtain a biological tissue repair composition. further,
Even for parts requiring more severe mechanical conditions, bioactivity can be imparted by coating the surface of biocompatible materials such as ceramics, metal materials, and organic polymer materials with excellent physical properties, especially It is suitably used as an implant material for tissue replacement that requires bonding with bone and soft tissue.

The present invention will be described specifically with reference to the following examples. The following is intended for illustrative purposes only, and is not limited to the following examples.

[0019]

Example 1 This is an example of preparing a putty composition using cellulose acetate as an organic polymer, ethyl lactate as an organic solvent, and tricalcium phosphate as a filler. 30 g of cellulose acetate was dissolved in 100 mL of ethyl lactate to obtain a liquid component. A sample obtained by subjecting the surface of the tricalcium phosphate powder to silane coupling treatment with 3-glycidoxypropyltrimethoxysilane was used as a solid component. After mixing at a solid component: liquid component ratio of 2.0: 1.0 (weight ratio), the mixture was heat-treated at 120 ° C. for 10 minutes to obtain a putty composition. This putty-like composition is 6 mm in diameter and 12 m in height.
m, and then immersed in distilled water at 37 ° C.
Held in. The mechanical properties of the putty composition were evaluated by compressive strength measurement using a material testing machine (Instron Digital Universal Material Testing Machine Model 5566). Using a 10 kN load cell, apply a compressive stress to the putty-like composition at a load speed of 20 mm / min until breakage occurs, and determine the compressive strength of the putty-like composition from the load at the time of the breakage and the cross-sectional area of the sample I asked. FIG. 4 shows the results. The shape of the putty-like composition could be freely changed until it was put into water. When this was immersed in water, it gradually lost its fluidity and hardened. The sample kept in water at 37 ° C. gave a compressive strength of about 5 MPa after 1 day and about 10 MPa after 7 days, and it was confirmed that it became a cured product.

Example 2 This is an example of preparing a putty composition using cellulose acetate as an organic polymer, ethyl lactate as an organic solvent, and hydroxyapatite powder having different particle sizes as a filler. Ethyl lactate
30 g of cellulose acetate was dissolved in 100 mL to obtain a liquid component. A sample obtained by subjecting the surface of a hydroxyapatite powder (manufactured by Ube Materials) having an average particle size of 1.5 μm or 16 μm to silane coupling treatment with 3-glycidoxypropyltrimethoxysilane was used as a solid component. In a hydroxyapatite powder having an average particle diameter of 1.5 μm, solid component: liquid component = 1.0: 1.0.
In (weight ratio), for a hydroxyapatite powder having an average particle diameter of 16 μm, a solid component: liquid component = 1.1: 1.0 (weight ratio), and then heat-treated at 120 ° C. for 10 minutes to obtain a putty composition. Was. This putty-like composition was formed into a column having a diameter of 6 mm and a height of 12 mm, and then immersed in distilled water and kept at 37 ° C. The mechanical properties of the putty composition were evaluated by compressive strength measurement using a material testing machine (Instron Digital Universal Material Testing Machine Model 5566). Using a 10 kN load cell, load speed 2
A compressive stress was applied to the putty-like composition at 0 mm / min until breakage occurred, and the compressive strength of the putty-like composition was determined from the load when the breakage occurred and the cross-sectional area of the sample. The result is shown in FIG. The shape of the putty-like composition could be freely changed until it was put into water. When this was immersed in water, it gradually lost its fluidity and hardened. The sample held at 37 ° C. in water after 7 days was about 14 MPa when using a hydroxyapatite powder having an average particle diameter of 1.5 μm, and about 3.5 MPa when using a hydroxyapatite powder having an average particle diameter of 16 μm. It was confirmed that it gave a compressive strength of MPa and became a cured product. The fluidity of the putty-like composition and the mechanical properties after curing depend on the particle size of the powder, and the mixing ratio of the solid component to the liquid component for obtaining the fluidity is different. It was confirmed that the putty-like composition changed into a cured product in water.

Example 3 Preparation of a putty composition using a powder obtained by mixing cellulose acetate as an organic polymer, ethyl lactate as an organic solvent, and tetracalcium phosphate and calcium hydrogen phosphate in a molar ratio of 1: 1 as a filler. This is an embodiment of the present invention. 30 g in 100 mL of ethyl lactate
Is dissolved to obtain a liquid component. 1 tetracalcium phosphate (4CaO · P ₂ O ₅₎ and anhydrous calcium hydrogen phosphate dihydrate (CaHPO ₄₎ in a molar ratio: silane mixed powder of the surface at 3-glycidoxypropyltrimethoxysilane to 1 The sample subjected to the coupling treatment was used as a solid component. This powder was converted to a solid component: liquid component = 2.2: 1.0
(Weight ratio) or 2.0: 1.0 (Weight ratio), mixed with the liquid component, and heat-treated at 120 ° C. for 10 minutes to obtain a putty composition. This putty-like composition was formed into a column having a diameter of 6 mm and a height of 12 mm, and then immersed in distilled water and kept at 37 ° C.
The mechanical properties of the putty-like composition were evaluated by compressive strength measurement using a material testing machine (Instron Digital Universal Material Testing Machine Model 5566). Using a 10 kN load cell, apply a compressive stress to the above putty-like composition at a load speed of 20 mm / min until breakage occurs. I asked. Figure 6 shows the results.
Shown in The shape of the putty-like composition could be freely changed until it was put into water. When this was immersed in water, it gradually lost its fluidity and hardened. The compressive strength of a sample held at 37 ° C in water is as follows: solid component: liquid component = 2.2: 1.0 (weight ratio)
After 7 days, it is about 19 MPa, and solid component: liquid component = 2.
At 0: 1.0 (weight ratio), about 28 MPa was achieved after 2 days. It was found that a putty composition that hardened in water was obtained even when the mixed filler was used, and that a high compressive strength was obtained by changing the ratio of the solid component to the liquid component.

Example 4 This is an example of preparing a putty composition using ethyl cellulose as an organic polymer, ethanol as an organic solvent, and tricalcium phosphate as a filler. 30 g in 100 mL of ethanol
Was dissolved to obtain a liquid component. Tricalcium phosphate (manufactured by Nacalai Tesque) powder was used as a solid component. This powder and liquid components are divided into solid components: liquid components = 1.6: 1.
The mixture was mixed at 0 (weight ratio) to obtain a putty composition. This putty-like composition was formed into a column having a diameter of 6 mm and a height of 12 mm, and then immersed in distilled water and kept at 37 ° C. The mechanical properties of the putty composition were evaluated by compressive strength measurement using a material testing machine (Instron Digital Universal Material Testing Machine Model 5566). Using a 10 kN load cell, applying a compressive stress at a load speed of 20 mm / min until the putty composition breaks,
The compressive strength of the putty-like composition was determined from the load when the fracture occurred and the cross-sectional area of the sample. FIG. 7 shows the results. The shape of the putty-like composition could be freely changed until it was put into water. When this was immersed in water, it gradually lost its fluidity and hardened. The compressive strength of the sample kept at 37 ° C. in water for 7 days has reached about 7.1 MPa. It was found that even when the combination of the organic polymer and the organic solvent was changed, a cured product could be formed by the same mechanism. It was also found that the surface treatment of the filler did not affect the curing phenomenon.

Example 5 This is an example of preparing a putty composition using copolylactide / glycolide as an organic polymer, ethyl lactate as an organic solvent, and tricalcium phosphate powder as a powder. 3 g of copolylactide / glycolide (Al
Poly (DL-lactide-co-glycolide) (85:15, average molecular weight Mw 50,000 to 75,000, manufactured by drich) was dissolved to obtain a liquid component. Tricalcium phosphate (manufactured by Nacalai Tesque) powder was used as a solid component. Solid component: liquid component = 3.3:
At 1.0 (weight ratio), the solid component and the liquid component were mixed to obtain a putty composition. This putty-like composition is 6 mm in diameter,
After shaping into a 12 mm high column, it is immersed in distilled water at 37 ° C
Held in. The mechanical properties of the putty composition were evaluated by compressive strength measurement using a material testing machine (Instron Digital Universal Material Testing Machine Model 5566). Using a 10 kN load cell, apply a compressive stress to the putty-like composition at a load speed of 20 mm / min until breakage occurs, and determine the compressive strength of the putty-like composition from the load at the time of the breakage and the cross-sectional area of the sample I asked. FIG. 8 shows the result. The shape of the putty-like composition could be freely changed until it was put into water. When this was immersed in water, it gradually lost its fluidity and hardened. It was confirmed that the sample kept at 37 ° C. in water gave a compressive strength of about 1.3 MPa after 7 days and was a cured product. Polylactide-based polymers are well-known bioabsorbable polymers, and by using them, it is possible to prepare a composition that is absorbed in a short time in a living body.

Example 6 Cellulose acetate as an organic polymer and lactic acid as an organic solvent
Ethyl, putty using bioactive glass powder as filler
1 is an example of preparing a liquid composition. 30 g to 100 mL of ethyl lactate
Cellulose acetate was dissolved to obtain a liquid component. Solid components
As Na ₂O-CaO-SiO₂−P₂O₅Ancestry
Crush bioactive glass and sieve to 45μm or less
The obtained powder was used. Powder to solid component: liquid component = 2.2:
At 1.0 (weight ratio), mix with liquid components and putty-like
A product was obtained. This putty-like composition is 6 mm in diameter and 12 mm in height.
After being formed into a cylindrical shape, immersed in distilled water and kept at 37 ° C
Was. The mechanical properties of the putty-like composition were measured using a material tester (instrument).
Compression strength using TRON Digital Universal Material Testing Machine Model 5566)
It was evaluated by degree measurement. Using a 10 kN load cell,
At a loading speed of 20 mm / min, the putty-like composition
To apply a compressive stress at
The compressive strength of the putty-like composition was determined from the area. The result
As shown in FIG. Putty-like composition can be freely shaped until put in water
Could be changed. When immersed in water,
First, it lost its fluidity and hardened. Trial held at 37 ° C in water
The compressive strength of the material has reached about 2.8 MPa after 7 days. Follow
Biocompatible fillers used in putty-like compositions
It can be seen that both crystalline and amorphous materials can be used.
Call

Example 7 This is an example of preparing a putty composition using ethyl cellulose as an organic polymer, triethyl phosphate as an organic solvent, and calcium hydroxide powder as a filler. Dissolve 20 g of ethyl cellulose in 100 mL of triethyl phosphate to make a liquid component. As a solid component, calcium hydroxide (manufactured by Nacalai Tesque) powder was used. This powder was mixed with the liquid component at a solid component: liquid component ratio of 1.6: 1.0 (weight ratio) to obtain a putty composition. This putty-like composition has a diameter of 6 mm and a height of
After forming into a 12 mm cylindrical shape, it was immersed in distilled water and kept at 37 ° C. The mechanical properties of the putty composition were evaluated by compressive strength measurement using a material testing machine (Instron Digital Universal Material Testing Machine Model 5566). Using a 10 kN load cell, apply a compressive stress to the putty-like composition at a load speed of 20 mm / min until breakage occurs, and determine the compressive strength of the putty-like composition from the load at the time of the breakage and the cross-sectional area of the sample I asked. The result is shown in FIG. The shape of the putty-like composition could be freely changed until it was put into water. When this was immersed in water, it gradually lost its fluidity and hardened. The compressive strength of the sample kept at 37 ° C in water reached about 3.4 MPa after 7 days.

[0026]

Industrial Applicability The present invention relates to a cement for fixing an artificial joint as a cement paste moldable in an operating room, a composition for repairing a living tissue filling a bone defect, and a material for repairing a living tissue. These can provide bioactivity by coating the surface of biocompatible materials such as ceramics, metal materials, and organic polymer materials with excellent physical properties, even for sites requiring more severe mechanical conditions. So
In particular, it has excellent effects in the medical industry, which is suitably used as a material for artificial bones that require bonding with bone.

[Brief description of the drawings]

FIG. 1 is a schematic view of an example of use of the present invention for a hip prosthesis.

FIG. 2 is a conceptual diagram of a curing mechanism of the putty composition of the present invention.

FIG. 3 is a schematic diagram of a procedure for synthesizing a putty composition of the present invention.

FIG. 4 shows the putty-like composition (organic polymer: cellulose acetate, organic solvent: ethyl lactate, filler: tricalcium phosphate) prepared in Example 1 immersed in water for 1 or 7 days. It is the result of measuring the compressive strength of the obtained cured product.

FIG. 5 is obtained by immersing the putty-like composition (organic polymer: cellulose acetate, organic solvent: ethyl lactate, filler: hydroxyapatite) prepared in Example 2 in water for 7 days. It is the result of measuring the compressive strength of the cured product. Hydroxyapatite powders (1.5 μm and 16 μm) having different average particle sizes were used.

FIG. 6 shows a putty-like composition prepared in Example 3 (organic polymer: cellulose acetate, organic solvent: ethyl lactate, filler: molar ratio of tetracalcium phosphate to calcium hydrogen phosphate: 1: 1). Is a result of measuring the compressive strength of a cured product obtained by immersing the cured product in water for 2 or 7 days.

FIG. 7 shows curing obtained by immersing the putty-like composition (organic polymer: ethyl cellulose, organic solvent: ethanol, filler: tricalcium phosphate) prepared in Example 4 in water for 7 days. It is the result of measuring the compressive strength of the body.

FIG. 8 shows the putty-like composition (organic polymer: copolylactide / glycolide, organic solvent: ethyl lactate, filler: tricalcium phosphate) prepared in Example 5 immersed in water for 7 days. It is the result of measuring the compressive strength of the obtained cured product.

FIG. 9 is obtained by immersing the putty-like composition (organic polymer: cellulose acetate, organic solvent: ethyl lactate, filler: bioactive glass) prepared in Example 6 in water for 7 days. It is the result of measuring the compressive strength of the cured product.

FIG. 10 is obtained by immersing the putty-like composition (organic polymer: ethyl cellulose, organic solvent: triethyl phosphate, filler: calcium hydroxide) prepared in Example 7 in water for 7 days. It is the result of measuring the compressive strength of the cured product.

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Toshiki Miyazaki 8916-5 Takayamacho, Ikoma City, Nara Prefecture University D-102 (72) Inventor Shinichi Ogata 8916-5 Takayamacho, Ikoma City, Nara University D-407 F-term (reference) 4C081 AB04 AB05 AC04 BA13 BA16 CA162 CA171 CA232 CC01 CD021 CD28 CE01 CE02 CE11 CF012 CF022 CF032 CF062 CF112 CF122 CF132 CF142 CF152 CF162 CF22 DA12 DA13 DA14 DC03 DC12

Claims (14)

[Claims] 1. A composition for repairing a living tissue, comprising: dissolving a biocompatible organic polymer compound that is soluble in an organic solvent and insoluble in water in an organic solvent that is compatible with water and adding a biocompatible filler thereto. object. 2. The composition for repairing a living tissue according to claim 1, wherein the biocompatible organic polymer compound is an organic polymer compound having low irritation to a living body. 3. The composition for repairing a living tissue according to claim 1, wherein the biocompatible organic polymer compound is cellulose acetate, ethyl cellulose, polylactide or copolylactide glycolide, or a mixture of two or more thereof. object. 4. The composition for repairing a living tissue according to claim 1, wherein the biocompatible filler is a biocompatible, bioactive or bioabsorbable filler. 5. The biocompatible filler is hydroxyapatite,
Tricalcium phosphate, tetracalcium phosphate, calcium phosphate, calcium carbonate, calcium silicate, calcium hydroxide, calcium oxide, calcium-containing glass, calcium silicate glass, calcium phosphate glass or bioactive glass or two or more of these The composition for repairing a living tissue according to claim 1, which is a mixture. 6. The material according to claim 1, wherein the biocompatible filler is a biocompatible filler which has been subjected to a surface treatment in advance. 7. The biocompatible filler is a biocompatible filler previously surface-treated with a silane coupling agent.
The material according to claim 6. 8. The composition for repairing a living tissue according to claim 1, which is a slurry, paste or putty composition. 9. The composition for repairing a living tissue according to claim 1, further comprising a reinforcing agent and / or a physiologically active agent. 10. The living tissue repair composition according to claim 9, wherein the reinforcing agent is alumina, silica, zirconia, titania, carbon, nylon or polyester, or a mixture of two or more thereof. 11. The composition for repairing a living tissue according to claim 9, wherein the physiologically active agent is an antibiotic, an anticancer agent, or an osteogenic factor. 12. A composition comprising a biocompatible organic polymer compound soluble in an organic solvent and insoluble in water, dissolved in an organic solvent compatible with water, and a biocompatible filler is added thereto. Material for repairing a living tissue obtained by contacting the same. 13. The implant material according to claim 12, wherein the composition is the composition for repairing a living tissue according to any one of claims 1 to 11. 14. An implant material obtained by coating the material according to claim 1 on a surface thereof.