JPH08229116A - Medical prosthetic material and its manufacture - Google Patents

Abstract

PURPOSE: To obtain a medical prosthetic material in which calcium phosphate is fixed firmly at a desired position on a base material shaped as desired and to provide a method for producing thereof advantageously. CONSTITUTION: In a medical prosthetic material comprising a calcium phosphate base material which enables adaptation to a wide ranging application and a part to be used, facilitates quality control with a lower production cost while being rich in biological affinity, calcium phosphate is deposited by a biochemical hydrolysis from calcium salt of an organic ester phosphate to be fastened firmly on a synthetic high polymer base material.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a medical prosthesis material comprising a calcium phosphate-coated synthetic polymer composite material and a method for producing the same, and more specifically, to biochemically hydrolyze a calcium salt of an organic phosphate ester and depositing the same. The present invention relates to a composite material obtained by firmly depositing calcium phosphate on a synthetic polymer substrate, and a method for producing the composite material.

[0002]

BACKGROUND ART Conventionally, surgical sutures, screws and rods for cortical bone and cancellous bone surgery, joint pins for rib fractures, hemostatic materials, adhesion prevention materials, artificial skin, artificial blood vessels, artificial esophagus, organ coating materials, A variety of medical prosthesis materials have been developed as organ inclusion materials, tissue repair materials, etc., which are implanted in a living body to protect or cover the tissues of the living body or substitute part or all of the tissues. There is.

In some of these materials,
A bioabsorbable material that is desired to disappear after a certain period of time is required, and in some cases, a living body that functions semi-permanently by substituting part or all of the living tissue to function. It is required to be a non-absorbent material. Therefore, in any case, it is required that the material embedded in the tissue is not biotoxic, stable and rich in biocompatibility.

In addition to the above required properties, in the case of sutures, such materials are required to have sufficiently high tensile strength, knot tensile strength, and elastic modulus close to that of living tissue. It is.

In the case of an osteosynthesis material such as a plate and a screw for osteosynthesis used in orthopedic surgery, oral surgery or thoracic surgery, the osteosynthesis material is biodegradable and resorbable and It is required to have the same elastic modulus as. Barefoot, bone cement material functions only until the fracture heals, and after healing, it needs to be removed as soon as possible to prevent weakening of the bone, and the bone joint material itself has a high elastic modulus. This is because there is a need to prevent the deterioration of bone due to passing.

Further, when it is used for covering an organ, a material having excellent biocompatibility has a high affinity so that it tends to cause adhesion with surrounding tissues after covering the target organ. The problem is inherent. That is,
Although such a material is advantageous for fixation between the implant and the organ, its adhesion to the surrounding tissue impedes the free movement of the organ after treatment and impairs functional recovery training. It will be. In particular, when used as a repair coating for a long term or semi-permanently in the body even after the protective coating of an organ, such as when used as a repair coating for a cut site of a tendon, the flexibility of the coating material Mechanical properties such as elasticity, high toughness, and high mechanical strength are required, and it is strongly desired not to cause adhesion with surrounding tissues. This is because the inhibition of the free movement of the organ after healing causes the patient great pain.

Furthermore, when an organic polymer is used as an artificial blood vessel, there is a problem that a pseudointimal membrane is easily formed and occlusion easily occurs. Therefore, the artificial blood vessel material absorbs blood coagulation factors. The development of an antithrombotic material having excellent flexibility and high mechanical strength is strongly desired.

[0008] By the way, it is well known that calcium phosphate materials, especially hydroxyapatite, have a bone-like composition and are excellent substitute materials for biological hard tissues, but in addition, they absorb blood coagulation factors. It has also been reported that the biomaterial has antithrombotic properties and further has excellent properties such as inhibition of growth of connective tissue and inhibition of foreign body reaction such as cell infiltration.

[0009] Then, some of the above-mentioned calcium phosphate-based materials, particularly medical prosthesis materials making use of the excellent characteristics of hydroxyapatite, have been developed and clinically studied.

Even the applicant of the present application has previously filed Japanese Patent Application No.
In No. 279625, as a medical prosthesis material useful for repairing tendon covering, a material in which a calcium phosphate-based material is adhered to and retained on one surface of a microbial cellulose substrate produced by microorganisms is disclosed. Such a medical prosthetic material utilizes the above-mentioned characteristics.
That is, such a medical prosthesis material is a calcium phosphate-based material, particularly one in which hydroxyapatite is coated on only one side of a microbial cellulose sheet substrate, and the surface consisting only of microbial cellulose is a tissue to be protectively coated, for example, Covers the severed tendon to protect its wound surface and helps in early healing of the wound and prevention of bacterial infections.
On the other hand, the surface coated with hydroxyapatite is
By arranging so as to be a surface that contacts the outer peripheral tissue, adhesion with the peripheral tissue can be prevented, and proliferation of connective tissue and antigen-antibody reaction can be suppressed. By preventing adhesion with surrounding tissues in this way, the function recovery training period after wound healing can be shortened without disturbing free movement of the tendon.

In the medical prosthesis material proposed by the applicant of the present application, a colloidal slurry of a calcium phosphate-based material is spread on a microbial cellulose gel or mixed with a microbial cellulose disaggregated gel during the production thereof. After that, after being spread in a sheet shape, dehydration, pressurization, heat drying to fix and coat the calcium phosphate-based material on only one side of the microbial cellulose sheet, and the target sheet-shaped medical prosthesis material is obtained. Thus, the hydroxyapatite-coated tendon-covering microbial cellulose sheet thus obtained was embedded in the periphery of the Achilles tendon of a rabbit and, even after one year, no foreign body reaction such as cell infiltration was observed. It is clear that it is an excellent prosthetic material that does not show adhesions to surrounding tissues at all. Than it was Tsu.

However, the present inventors have further found that a medical prosthesis material comprising a microbial cellulose sheet substrate having one surface coated with such a calcium phosphate-based material still has a problem to be improved. It became clear by the examination. That is, it is that the prosthetic material produced by the above-mentioned method is a composite in which calcium phosphate is mechanically attached to one surface of microbial cellulose gel. In this case, when it is embedded as a biomaterial for a long period of time, it cannot be said that the calcium phosphate once adhered is not likely to peel off during the implantation, and further strong fixation is desired.

Further, when used as a prosthetic material for tendon repair, it is easier to handle the microbial cellulose base material in a hollow cylindrical shape than in a sheet shape when performing surgery. In addition, in order to prevent adhesion to surrounding tissues, it is desirable that calcium phosphate is firmly and uniformly fixed to the outside of the hollow cylindrical substrate. On the other hand, when such a hollow cylindrical substrate is used as an artificial blood vessel, calcium phosphate such as hydroxyapatite has an antithrombotic property, so that calcium phosphate is firmly fixed inside the hollow cylindrical sheet. Is desirable. In addition to this, there are cases where it is desired to firmly fix calcium phosphate only to a limited local portion of a base material having a complicated shape. To satisfy such various requirements, it is disclosed in Japanese Patent Application No. 5-279625. Such a mechanical fixing method of calcium phosphate cannot sufficiently cope with the problem.

Further, a medical prosthesis material comprising a microbial cellulose sheet base material coated on one side with such a calcium phosphate-based material is, depending on the physical properties of the microbial cellulose base material, depending on the purpose and site of use other than for tendon repair. Has a problem that the production cost is high and the quality control is difficult because microbial cellulose is a natural polymer.

On the other hand, in addition to Japanese Patent Application No. 5-279625, various medical organic polymer materials coated with calcium phosphate, such as hydroxyapatite, are used as artificial blood vessels, wound covering materials, medical prosthesis materials, and the like. , Which have been reported so far, for example, 1) A mixture of collagen or sodium alginate and calcium phosphate, and dried (JP-A-1-20707).
No. 2, JP-A-1-502652), 2) A method of forming a sheet by extruding a mixture of alginic acid, collagen, polyvinyl alcohol or hyaluronic acid and hydroxyapatite into a fiber (JP-A-1-288269). Gazette), 3) Hydroxyapatite-containing organic polymer sheet or granules (JP-A-2-77262, JP-A-3-199)
113, JP-A-5-123390), 4) By immersing an organic polymer such as polyester, polyacrylonitrile, or polyurethane in a bioglass-containing artificial body fluid, hydroxyapatite is deposited on the surface of these organic polymers. Method (JP-A-5-31740)
No. 8) is disclosed.

However, although many techniques have been proposed in this way, many problems still remain with respect to the method of attaching, fixing, and coating calcium phosphate, for example, the method of 4) above. Except for the above, it is merely a composite material in which calcium phosphate such as hydroxyapatite is impregnated or mechanically mixed, and it is difficult to fix calcium phosphate only on any limited surface, and it is not always necessary to prevent adhesion. It was hard to say that it is suitable as a medical prosthesis material. In addition, the method of 4) is a method in which hydroxyapatite is chemically deposited, and although it can be said that it is a more uniform coating method, it is necessary to prepare bioglass in advance and to use a polymer material. However, there is an inherent problem that it is difficult to bond it to only one side.

[0017]

Here, in view of the above circumstances, the present invention has been earnestly studied for the purpose of improving a new base material that replaces the base material in the existing calcium phosphate-based coating composite material and a fixing method for the base material. As a result of repeating the above, the problem is that it can be applied to a wide range of purposes and sites as a medical prosthesis material, the production cost is low, and the quality control is easy. To provide a medical prosthesis material comprising a calcium-phosphate-coated base material rich in biocompatibility, wherein calcium phosphate is firmly fixed at a desired position on a base material having a desired shape, and a method for advantageously producing the same. It is in.

[0018]

In order to solve the above problems, the present invention uses a synthetic polymer substrate having a desired shape, which is made of a synthetic polymer having a high biocompatibility. The gist of the present invention is a medical prosthesis material characterized in that calcium phosphate is precipitated from a calcium salt of an organic phosphate ester by a biochemical hydrolysis reaction and firmly fixed thereto.

In a preferred first aspect of the present invention, the calcium phosphate is precipitated in the state of amorphous calcium phosphate, hydroxyapatite precursor, or crystalline carbonic acid-containing hydroxyapatite.

Further, in a preferred second aspect of the present invention, the synthetic polymer is selected from the group consisting of polyglycolic acid, polylactic acid, glycolic acid / lactic acid copolymer, polyester, polycarbonate and nylon. Become.

Furthermore, in a preferred third aspect of the present invention, the calcium salt of the organic phosphate is β
-Calcium glycerophosphate, by the biochemical hydrolysis reaction of this β- calcium glycerophosphate,
The hydroxyapatite as the calcium phosphate is firmly fixed on the synthetic polymer substrate.

On the other hand, according to the present invention, in order to obtain such a medical prosthesis material, a base material having a desired shape made of a synthetic polymer having a high biocompatibility is used, and an organic phosphoric acid is applied onto the synthetic polymer base material. A gist of the present invention is also a method for producing a medical prosthesis material characterized in that calcium phosphate generated by a biochemical hydrolysis reaction of a calcium salt of an ester with alkaline phosphatase is deposited and firmly fixed.

Further, in the first preferred embodiment of the method of the present invention, the calcium salt of the organic phosphate is β-glycerophosphate, and hydroxyapatite is precipitated as the calcium phosphate by the hydrolysis reaction. It will be.

Further, in a second preferred embodiment of the method of the present invention, the precipitation of calcium phosphate by the hydrolysis reaction of the calcium salt of the organic phosphate is carried out by preliminarily crosslinking phosvitin in the presence of dimethylsuberoimidate. This is carried out on the synthetic polymer base material, whereby the precipitation of calcium phosphate can be proceeded more effectively.

By the way, the point that the present invention as described above is fundamentally different from the conventional hydroxyapatite coating method is as follows.
As a means for depositing and fixing calcium phosphate such as hydroxyapatite on a synthetic polymer substrate, a biochemical hydrolysis reaction of an organic phosphate calcium salt by alkaline phosphatase is used.

That is, alkaline phosphatase is
Calcium salt of an organic phosphate ester, which is an enzyme that is present on the cell membrane of osteoblasts and is considered to be closely related to calcification of osteoblasts, is hydrolyzed by this alkaline phosphatase to give inorganic calcium phosphate. It will precipitate. Regarding the complexation of hydroxyapatite and collagen using this reaction, see E.
Banks et al., "Science", 198 , 1164-.
1166 (1977) and Doi et al., "Dental materials and equipment"
9 , 863-870 (1990), "Dental materials and equipment"
10 , 814-819 (1991).

By the way, according to the report of Banks et al. And Doi et al., In utilizing the hydrolysis reaction of calcium β-glycerophosphate by alkaline phosphatase, apatite or apatite precursor is precipitated in collagen alone, but Assuming that it is not firmly adhered to the collagen fiber, cross-linking phosphoprotein etc. to collagen creates conditions closer to the biological environment, and as a result, for the first time, apatite can be fixed and deposited on collagen. It has been revealed. And
Probably, a relatively weak intermolecular force bond different from covalent bond or ionic bond is formed between collagen fiber and hydroxyapatite, which explains that it chemically bonds collagen and hydroxyapatite. Has been done.

In the case of a prosthesis material for preventing adhesion, which requires flexibility and high mechanical strength retention for a considerably long period of time, such as tendon repair, The use of a composite material prepared by precipitating calcium phosphate on collagen as proposed in 1) is not appropriate because collagen itself is weak in strength, and when collagen is used as a base material, a prosthesis of any form is obtained. It is difficult to mold materials such as hollow tubular substrates, and because collagen is a natural polymer, the production cost is high,
There is an inherent problem that quality control is difficult.

In the present invention, however, a synthetic polymer having biocompatibility is selected as the substrate, and the calcium salt of the organic phosphate ester is deposited on the synthetic polymer substrate. We have found the fact that inorganic calcium phosphates such as hydroxyapatite can be firmly anchored and retained, as in the case of chemical bonding, and thereby complete the invention.

In the present invention, calcium phosphate such as hydroxyapatite, which is precipitated from the calcium salt of an organic phosphoric acid ester, chemically reacts with a synthetic polymer having high biocompatibility as in the case of collagen. It has not been sufficiently confirmed whether or not it is bound to, but as a result of the present inventors, as a fixing method, as a result of diligent examination of application and improvement of the above method developed by Banks et al. And Doi, Rather, it was clarified that hydroxyapatite (calcium phosphate) was strongly deposited and fixed on the synthetic polymer rather than collagen. Therefore, between the synthetic polymer and hydroxyapatite (calcium phosphate), It is thought that some chemical bonds are formed that are much stronger than collagen. And is're.

[0031]

Concrete Structure By the way, in the present invention as described above,
As a synthetic polymer material used as a base material, which has biocompatibility and gives an excellent medical prosthesis material having appropriate physical properties according to its intended purpose and site of use, it is biodegradable and absorbable. Regardless of whether it is a polymer or non-degradable absorbable polymer, it has already been widely used in biomaterials such as bioimplant materials and surgical sutures, and sufficiently analyzed in-vivo mechanical properties and biocompatibility. In addition, in the case of biodegradable and absorbable polymers, those that have also been analyzed in vivo degradation and absorption processes are selected, for example,
Known materials such as polyglycolic acid, polylactic acid, glycolic acid / lactic acid copolymer, polyester, polycarbonate and nylon can be mentioned. Among these synthetic polymer materials, those having physical properties suitable for the purpose and site of use of the medical prosthesis material can be appropriately selected.

The synthetic polymer material that constitutes such a base material is used in a desired shape suitable for the purpose and site of use, such as a filament, a thin film sheet, a hollow tube, or the like. In addition, a known manufacturing method is appropriately used for manufacturing a synthetic polymer substrate having a desired shape.

On the other hand, as a calcium salt of an organic phosphoric acid ester which produces a calcium phosphate precipitated on such a synthetic polymer substrate by a hydrolysis reaction,
There are adenosine triphosphate calcium, monophenyl calcium phosphate, β-glycerophosphate calcium, etc.,
Particularly in the present invention, β-glycerophosphate calcium is advantageously used. This β-glycerophosphate is hydrolyzed by alkaline phosphatase to give hydroxyapatite (calcium phosphate).
, And the hydroxyapatite thus deposited firmly adheres to the synthetic polymer substrate.

The calcium salt of an organic phosphate ester such as β-glycerophosphate is precipitated by a hydrolysis reaction with alkaline phosphatase.
The type of crystal phase of calcium phosphate such as hydroxyapatite and the initiation time of precipitation are affected by the initial concentration of alkaline phosphatase, pH, temperature and the like. That is, when the initial concentration of alkaline phosphatase is high, it tends to become amorphous calcium phosphate, and as the concentration decreases, from the apatite precursor to the carbonic acid-containing hydroxyapatite, by adjusting the initial concentration of alkaline phosphatase. It is possible to change the crystal phase of precipitated calcium phosphate. by this,
It is possible to coat calcium phosphate having various properties from amorphous calcium phosphate to hydroxyapatite precursor to crystalline carbonate-containing hydroxyapatite. For example, as the concentration for depositing hydroxyapatite, a concentration of 2 to 20 mMol, and preferably 4 to 8 mMol will be adopted. In addition, since alkaline phosphatase activity is higher in the basic region than in the neutral region, the pH is preferably basic, and in general, in the range of pH 8 to 10, preferably pH 8.5 to 9.5, the hydrolysis reaction is It is desirable that the temperature be set to about 37 ° C. in consideration of a biomimetic environment.

In the present invention, calcium phosphate produced by a biochemical hydrolysis reaction from such a calcium salt of an organic phosphate is precipitated on a synthetic polymer substrate having a desired shape, Although it firmly anchors, in such hydrolysis reaction, as in the case of collagen, phosvitin (phosphoprotein derived from egg yolk) is used as a phosphorus cross-linking agent and dimethyl suberoimidate is used as a cross-linking accelerator. It is desirable to allow it to be present in the system, which can favorably accelerate the precipitation reaction. However, in the case of using the synthetic polymer as a base material in the examples of the present invention, calcium phosphate such as hydroxyapatite can be added at a considerable precipitation rate without using a crosslinking accelerator such as dimethylsuberoimidate. It is also possible to deposit on such a synthetic polymer substrate.

Phosvitin has a molecular weight of about 400.
00 is a phosphoprotein containing about 10% of organic phosphoric acid, but in the case of collagen, it is produced by hydrolysis reaction from calcium salt of organic phosphoric acid ester due to the catalytic effect of alkaline phosphatase. Inorganic calcium phosphate is believed to chemically bind to the surface of collagen cross-linked with phosvitin.
Furthermore, it is believed that cross-linked phosvitin enhances alkaline phosphatase activity and promotes the production of inorganic calcium phosphate, which leads to faster and more calcium phosphate deposition. Thus, even for the synthetic polymer used in the present invention, like collagen,
Whether phosvitin is cross-linked to a synthetic polymer and whether it accelerates the precipitation of calcium phosphate,
Although not fully clarified yet, according to the studies by the present inventors, it has been clarified that the precipitation reaction can be promoted similarly to collagen or more. Then, they found that the precipitated calcium phosphate adhered to the synthetic polymer base material more firmly than collagen. It was confirmed that, under the above reaction conditions in which the initial concentration of alkaline phosphatase was 2 to 20 mMol, the precipitated hydroxyapatite phase of calcium phosphate was carbonic acid-containing hydroxyapatite having low crystallinity and resembling hard tissue.

The calcium phosphate deposited according to the present invention can be fixed to any suitable site according to the purpose and site of use of the medical prosthesis material, regardless of the shape of the synthetic polymer base material. It is possible. The site of the synthetic polymer substrate in which it is desired to avoid such fixation of calcium phosphate will be coated with a suitable other material. Further, as the thickness of the fixed layer of calcium phosphate to be deposited, it can be arbitrarily changed by selecting the deposition conditions, depending on the purpose and site of use as a medical prosthesis material,
The thickness will be appropriate.

[0038]

EXAMPLES In order to clarify the present invention in more detail, some examples of the present invention will be shown below.
It goes without saying that the present invention is not limited by the description of such embodiments. In addition, in addition to the following examples, the present invention, in addition to the above-described specific description, various changes, corrections, and modifications based on the knowledge of those skilled in the art without departing from the spirit of the present invention. It should be understood that improvements can be made.

Example 1 First, in order to obtain a crystalline carbonic acid-containing hydroxyapatite-coated medical prosthesis material, the following five reaction solutions were prepared.

That is, as the pH buffer solution (solution A), p
A 200 mMol Tris buffer adjusted to H8.5 was prepared, and a 0.04% alkaline phosphatase solution (solution B) was prepared using this pH buffer as a solvent. Further, as a phosvitin solution (solution C), a solution prepared by dissolving 0.04% phosvitin in a solvent composed of the pH buffer solution was prepared. Further, the dimethyl suberoimidate solution (solution D) was added to the solvent composed of the pH buffer solution,
It was prepared as a solution prepared by dissolving 0.3% dimethyl suberoimidate, and a β-calcium glycerophosphate solution (solution E) was prepared by dissolving 6 mMol β-glycerophosphate calcium in a solvent consisting of the pH buffer solution. Was prepared as a solution.

Then, using a polyglycolic acid filament, liquid B, liquid C and liquid D prepared above were respectively added thereto, and the mixture was allowed to stand at a temperature of 37 ° C. for 6 days, and then the solution was removed. By washing with distilled water,
Phosvitin crosslinking of the polyglycolic acid filament (base material) was performed.

Next, to the obtained crosslinked polyglycolic acid filaments, the solutions C and D prepared above were added, and the mixture was allowed to stand at room temperature for 3 hours, then the solution was removed and prepared above. Solution E was added and the temperature was 37 ° C for 20
The polyglycolic acid filament was covered with the crystalline carbonic acid-containing hydroxyapatite by standing for a time. The thickness of the crystalline carbonic acid-containing hydroxyapatite coating layer (fixed layer) was adjusted by repeating this operation several times.

In this way, the crystalline carbonic acid-containing hydroxyapatite layer having a thickness of several μ could be firmly coated on the surface of the polyglycolic acid filament.

Example 2 Solution D (dimethylsuberoimidate solution), which is a crosslinking accelerator in the above-mentioned polyglycolic acid filament crosslinking.
In the same manner as in Example 1 except that the cross-linking agent was not used and the cross-linking was performed using only the solutions B and C, in other words, the crystalline carbonic acid for the polyglycolic acid filament was used. The contained hydroxyapatite was coated. As a result, it was possible to coat the surface of the polyglycolic acid filament with a crystalline carbonic acid-containing hydroxyapatite layer having a thickness of several μm without using a crosslinking accelerator.

Example 3 A crystalline carbonic acid-containing hydroxyapatite was coated in the same manner as in Example 1 except that a polydioxanone filament was used as the substrate. As a result, even in this case, a crystalline carbonic acid-containing hydroxyapatite coating layer having a thickness of several μ could be formed on the surface of the polydioxanone filament.

Example 4 A crystalline carbonic acid-containing hydroxyapatite coating was carried out in the same manner as in Example 1 except that glycolide / trimethylene carbonate copolymer filaments were used as the substrate. As a result, even in this case, a crystalline carbonic acid-containing hydroxyapatite coating layer having a thickness of several μ could be formed on the surface of the glycolide / trimethylene carbonate copolymer filament.

Example 5 Except that a nylon filament is used as the base material,
In the same manner as in Example 1, the crystalline carbonic acid-containing hydroxyapatite coating was performed. As a result, a crystalline carbonic acid-containing hydroxyapatite coating layer having a thickness of several μm could be formed on the surface of the nylon filament.

Example 6 A crystalline carbonic acid-containing hydroxyapatite coating was carried out in the same manner as in Example 1 except that a polyester filament was used as the base material. As a result, a crystalline carbonic acid-containing hydroxyapatite coating layer having a thickness of several μm could be formed on the surface of the polyester filament.

[0049]

As is apparent from the above description, the medical prosthesis material according to the present invention has a high biocompatibility, and the calcium phosphate coating layer formed at a predetermined site on the surface of the medical prosthesis material is a medical prosthesis. It is characterized by firmly adhering to a synthetic polymer substrate having appropriate physical properties according to the purpose of use and site of use of the material, and such a strongly adhering calcium phosphate coating layer is Regardless of the shape of the molecular base material, it can be formed at any appropriate site depending on the purpose and site of use.
Therefore, such a medical prosthesis material has properties that are very suitable for the intended purpose and site of use, and is of great technical significance as a medical prosthesis material.

Moreover, since such a medical prosthesis material according to the present invention uses a synthetic polymer that is artificially manufactured as a base material, the production cost can be reduced and the quality control can be facilitated. There is a feature.

Further, according to the method for producing a medical prosthesis material according to the present invention, it is possible to advantageously obtain a medical prosthesis material having the above-mentioned excellent characteristics, and in particular, phosvitin and dimethyl suberoimidate are used. Thus, the calcium phosphate coating layer can be effectively formed.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Hajime Saito 7-1409 Higashiyama, Nisshin City, Aichi Prefecture (72) Inventor Shigerou Niwa 2-1213 Goshikinen, Nisshin City, Aichi Prefecture (72) Inventor Yoshiro Sato Nakagawa, Nagoya City, Aichi Prefecture 2-19-3 Ward Ogashirabashi

Claims (7)

[Claims] 1. A substrate having a desired shape, which is made of a synthetic polymer having a high biocompatibility, is used, and a calcium salt of an organic phosphate ester is biochemically hydrolyzed on the synthetic polymer substrate. A medical prosthesis material characterized in that calcium phosphate is precipitated and firmly fixed. 2. The calcium phosphate is amorphous calcium phosphate, a hydroxyapatite precursor, or crystalline carbonic acid-containing hydroxyapatite.
The medical prosthesis material according to. 3. The synthetic polymer is polyglycolic acid,
The medical prosthetic material according to claim 1 or 2, which is selected from the group consisting of polylactic acid, glycolic acid / lactic acid copolymer, polyester, polycarbonate, and nylon. 4. The calcium salt of the organic phosphate ester is β-glycerophosphate, and hydroxyapatite as the calcium phosphate is converted into the synthetic polymer base material by a biochemical hydrolysis reaction of the β-glycerophosphate. The medical prosthesis material according to any one of claims 1 to 3, which is firmly fixed to the top. 5. A biochemical hydrolysis of a calcium salt of an organic phosphoric acid ester by alkaline phosphatase on a substrate having a desired shape, which is made of a synthetic polymer having high biocompatibility. A method for producing a medical prosthesis material, which comprises depositing calcium phosphate generated by a reaction and firmly fixing the calcium phosphate. 6. The method for producing a medical prosthetic material according to claim 5, wherein the calcium salt of the organic phosphate ester is β-glycerophosphate, and hydroxyapatite is precipitated as the calcium phosphate by a hydrolysis reaction thereof. . 7. Precipitation of calcium phosphate by a hydrolysis reaction of the calcium salt of the organic phosphate ester is carried out on the synthetic polymer base material obtained by previously crosslinking phosvitin in the presence of dimethylsuberoimidate. Item 5. A method for producing the medical prosthetic material according to Item 5 or 6.