WO2006022018A1 - Process for producing bone treatment implement and bone treatment implement - Google Patents

Abstract

A process for producing a bone treatment implement that is composed of a composite material of biodegradable polymer and bioceramic, excelling in mechanical characteristics such as strength; and a bone treatment implement produced by the process. There is provided a process for producing a bone treatment implement composed of a composite material having bioceramic microparticles dispersed in a matrix of biodegradable polymer, comprising at least the step (1) of forming a coating layer of the biodegradable polymer on the surface of the bioceramic microparticles; the second step (2) of kneading the bioceramic microparticles furnished with the coating layer together with the biodegradable polymer at a temperature not lower than the melting point of the biodegradable polymer to thereby obtain a kneaded composition; and the step (3) of forming the kneaded composition into a shaped item.

Description

 Specification

 Bone treatment tool manufacturing method and bone treatment tool

 Technical field

 TECHNICAL FIELD [0001] The present invention relates to a method for producing a bone treatment device that is made of a composite material of a biodegradable polymer and bioceramics and has excellent mechanical properties such as strength, and a bone treatment device that uses the production method. .

 Background art

Conventionally, wires, plates, screws, pins, screws, staples, clips, rods, and the like made of stainless steel, ceramic, and the like have been used as bone treatment tools. However, bone healing tools made of metal or ceramics are not absorbed by the human body, so it was necessary to re-operate for removal after healing. These osteotherapeutic utensil, stainless steel 323N / mm ² approximately by those of SUS-316, those of ceramic 245- and 490 N / mm ² degree, while having practically sufficient flexural strength, human bone The bones of the applied part may be shaved, or the bone may be melted locally, the strength of the new bone may be reduced, the growth of the regenerated bone may be delayed, etc. was there.

[0003] On the other hand, bone treatment tools made of biodegradable polymers such as poly_L_lactic acid have been developed. For example, Patent Document 1 discloses that a biodegradable polymer molding is hydrostatically extruded at a temperature not lower than the glass transition point and not higher than the melting point of the polymer so that the biodegradable polymer molecules are aligned in the major axis direction. A bone treatment device is disclosed which is an oriented high-density molded body having a density measured by a floatation method of 1. 260 g / cm ³ or more. This bone treatment tool is extremely excellent as a bone treatment tool because it is bioabsorbable and therefore does not need to be removed after healing, and maintains appropriate strength and rigidity during the period required for healing.

[0004] In recent years, development of bone treatment devices containing bioceramics such as hydroxyapatite, which is considered to have excellent osteoconductivity and promote osteogenesis, has been promoted from the viewpoint of achieving higher therapeutic effects. Also, composites of biodegradable polymers and bioceramics are being studied. For example, a method of dispersing bioceramic powder in a biodegradable polymer has been tried. However, since the biodegradable polymer and the bioceramics generally have insufficient affinity, the mechanical properties such as strength of the bone treatment device formed by combining these are composed of the biodegradable polymer alone. There was a problem that it became lower than the one.

 [0005] Further, in Patent Document 2, biocompatible and bioactive bioceramics powder is embedded in the surface layer portion of a main body made of a thermoplastic organic polymer material that is bioinert or biodegradable and absorbable. And an exposed implant material is disclosed. However, even with this method, the strength of the resulting implant material is insufficient because it is necessary to soften the surface layer part by heating the body itself to load the bioceramic powder onto the surface. Met.

 [0006] Patent Document 1: Japanese Patent No. 2619760

 Patent Document 2: Japanese Patent Laid-Open No. 9-173435

 Disclosure of the invention

 Problems to be solved by the invention

[0007] In view of the above situation, the present invention is made of a composite material of a biodegradable polymer and bioceramics, and uses a method for manufacturing a bone treatment tool excellent in mechanical properties such as strength. An object is to provide a bone treatment tool.

 Means for solving the problem

 [0008] The present invention is a method for manufacturing a bone treatment device having a composite material force in which bioceramics fine particles are dispersed in a matrix made of a biodegradable polymer, and at least the surface of the bioceramics fine particles has the above-mentioned A kneaded product obtained by kneading step 1 for forming a coat layer made of a biodegradable polymer, bioceramics fine particles on which the coat layer is formed, and the biodegradable polymer at a temperature equal to or higher than the melting point of the biodegradable polymer This is a method for producing a bone treatment tool, which includes the step 2 for obtaining the above and the step 3 for obtaining a molded product from the kneaded product.

 The present invention is described in detail below.

[0009] As a result of intensive studies, the present inventors have improved the affinity with the biodegradable polymer by forming a coating layer made of the biodegradable polymer in advance on the surface of the bioceramic fine particles, and the resulting composite It has been found that a bone treatment tool made of a material has mechanical properties such as strength equivalent to those made of a biodegradable polymer alone, and has completed the present invention. The present invention is a method for producing a bone treatment device having a composite material force in which bioceramic fine particles are dispersed in a matrix made of a biodegradable polymer.

 [0010] The biodegradable polymer is not particularly limited as long as it has a property of being hydrolyzed in vivo and absorbed by the living body. For example, poly_L_lactic acid, poly_D_lactic acid, poly_D , L monolactic acid, L monolactic acid and D-lactic acid copolymer, L monolactic acid and D, L monolactic acid copolymer, D_lactic acid and D, L-lactic acid copolymer, poly _L_lactic acid Poly_D_lactic acid blended stereocomplex, polydalicolic acid, L-lactic acid and glycolic acid copolymer, D_lactic acid and glycolic acid copolymer, D, L monolactic acid and glycolic acid copolymer, etc. Is suitable. Among these, lactic acid homopolymers or copolymers are more preferred. Poly-L-lactic acid, L-monolactic acid-based copolymer of L-monolactic acid and D-lactic acid, L-lactic acid-based material A copolymer of L lactic acid and D, L monolactic acid, or a stereocomplex force obtained by blending poly_L_lactic acid and poly-D-lactic acid is preferred because of its excellent strength and strength retention. These biodegradable polymers may be used alone or in combination of two or more.

 [0011] The molecular weight of the biodegradable polymer is not particularly limited, but the polymer itself tends to decompose due to heat and cause a decrease in the molecular weight. In view of the decrease in the molecular weight during production, the raw material before molding The weight average molecular weight of the polymer by GPC method is preferably 100,000 or more. Of these, those having a weight average molecular weight force of about S150,000 to 500,000 are preferable from the viewpoints of degradability, strength retention, workability, cost, and the like.

 [0012] In the present specification, the bioceramics are biologically related ceramics, which are ceramics that are used for transplantation or contact directly with the human body to restore or enhance biological functions.

Examples of the bioceramics include hydroxyapatite, bioglass, ceravital, apatite wollastonite glass ceramics, tritricalcium phosphate, / 3-tricalcium phosphate, tetracalcium phosphate, octacalcium phosphate, tetracalcium phosphate. Examples include “dicalcium phosphate dihydride, tetracalcium phosphate” dicalcium phosphate, and the like. Of these, hydroxyapatite, which is excellent in osteoconductivity and osteogenic ability, is preferable. These bioceramics may be used alone or in combination of two or more. [0013] When hydroxyapatite is used as the bioceramic, it is preferable to use one that is fired at a temperature of about 900 ° C. Unsintered hydroxyapatite may have poor bone conductivity and may be contaminated with organic impurities due to unsintering. Hydroxyapatite baked at a high temperature of about 1200 ° C or higher may have poor osteoconductivity, and the resulting bone treatment tool may have poor strength.

 [0014] The shape of the bioceramic fine particles is not particularly limited, and examples thereof include a spherical shape, a rod shape, a plate shape, a thin film shape, a fiber shape, and a tube shape. Moreover, a structure having fine protrusions on the surface of fine particles having these shapes may be used.

 The particle size of the bioceramic fine particles is not particularly limited, but the preferred lower limit is l × m and the preferred upper limit is 100 × m. : If it is less than m, it may cause an inflammatory reaction due to macrophage phagocytosis when used in vivo, and if it exceeds 100 zm, the dispersibility may deteriorate and the strength of the resulting bone treatment device may vary. A more preferred lower limit is 5 μΐη, a more preferred upper limit is 70 μΐη, a still more preferred lower limit is 10 μm, and a more preferred upper limit is 50 / im.

[0015] In the method for producing a bone treatment device of the present invention, first, Step 1 of forming a coat layer made of a biodegradable polymer on the surface of the bioceramic fine particles is performed.

 The biodegradable polymer constituting the coating layer may be different from the biodegradable polymer used in the matrix as long as it has excellent compatibility, but it is preferable to use the same type.

 [0016] The coat layer is preferably formed uniformly on the surface of the bioceramic fine particles, but may be partially formed.

 The amount of the coating layer deposited is not particularly limited, but the preferred lower limit is 1% by weight with respect to the bioceramic fine particles. If it is less than 1% by weight, a sufficient effect of promoting the combination may not be obtained. A more preferred lower limit is 5% by weight. There is no particular upper limit on the amount of the coating layer deposited, but about 25% by weight is preferred, and a more preferred upper limit is 20% by weight.

[0017] As a method of forming a coat layer on the surface of the bioceramics fine particles, the above-mentioned bio Examples thereof include a dip method in which ceramic fine particles are immersed in the biodegradable polymer solution and then dried using an evaporator or the like; a spray dry method in which the ceramic fine particles are dried in a spray state.

 In addition, when forming a coat layer by the dip method or spray drying method, it is preferable to form a desired coat layer only by one cycle of immersion-drying operation. A coat layer may be formed.

 Examples of the solvent for the biodegradable polymer include black mouth form, chloromethylene, 1,4-dioxane, and the like.

[0018] In the method for producing a bone treatment device of the present invention, the bioceramics fine particles having a coating layer formed thereon and the biodegradable polymer are kneaded at a temperature equal to or higher than the melting point of the biodegradable polymer to prepare a kneaded product. Step 2 is performed.

 The kneading method is not particularly limited. For example, a method using a mixer such as a homodisper, a homomixer, a universal mixer, a planetarium mixer, an adader, a three-roller, or a method of mixing in a twin screw extruder or the like. A conventionally known method such as the above can be used.

 [0019] The mixing ratio of the biodegradable polymer and the bioceramic is not particularly limited, but the preferable lower limit of the blending amount of the bioceramic with respect to the entire composite material is 10% by weight, and the preferable upper limit is 50% by weight. If it is less than 10% by weight, the excellent effects of bioceramics such as osteoconduction and osteogenesis may not be obtained. If it exceeds 50% by weight, the strength of the obtained bone treatment tool may be inferior. A more preferred lower limit is 20% by weight, and a more preferred upper limit is 40% by weight. If the amount of bioceramics is 30% by weight or more, the resulting bone treatment material has excellent X-ray contrast properties, which is preferable.

 [0020] In the method for manufacturing a bone treatment device of the present invention, step 3 of obtaining a molded product from the kneaded product obtained in step 2 is then performed. The molding method is not particularly limited, and for example, a known method such as an extrusion molding method can be used.

 The molded product thus obtained has mechanical properties such as strength comparable to that of a molded product composed of a biodegradable polymer alone, despite containing the bioceramics.

[0021] In the method for producing a bone treatment tool of the present invention, the molded product obtained in the above step 3 is further treated with a raw material. It is preferable to carry out a process such as isostatic extrusion, tensile stretching, drawing stretching, or the like at a temperature not lower than the melting point and not higher than the melting point of the polymer. The bone treatment device thus obtained is a high-density body in which biodegradable polymer molecules are oriented in the major axis direction, and maintains appropriate strength and rigidity during the period required for healing. It will be extremely excellent.

 [0022] The hydrostatic extrusion method is, for example, an object to be extruded in the configuration of an extrusion apparatus including an extrusion container (1), a die (2), and an extrusion ram (3) as shown in FIG. The space (5) between the polymer (4) and the extrusion container (1) is filled with, for example, glycerin as a pressure medium, and pressure is applied by applying pressure in the P direction to the ram (3) under this heating. Indirect extrusion of the polymer through the medium.

 [0023] In addition, the method shown in FIG. 2 is a method called differential pressure extrusion in which the space portion (7) of the extruded side container (6) is filled with a pressure medium facing the extrusion side, Although not shown, the effect of higher pressure can be expected by applying a pressure (P2) that is weaker than the extrusion pressure (P1) from the opposite direction by the ram. Furthermore, as shown in FIG. 3, extrusion can be performed while pulling out in the F direction, thereby ensuring the straightness of the extrudate and a good surface condition.

 [0024] In the case of stretching by the hydrostatic extrusion method, it is preferable to extrude at a temperature not lower than the glass transition point and not higher than the melting point of the biodegradable polymer. In particular, extrude at temperatures slightly below the melting point, for example, in the range of 90-170 ° C for poly_L_lactic acid, 120-220 ° C for polydaricholic acid, and 80-170 ° C for copolymers. Is preferred.

 [0025] The extrusion ratio is preferably in the range of 2 to 10 times. For example, when the biodegradable polymer is poly L monolactic acid, the extrusion ratio is 2. ± 20 ° C. The optimal range is 5-6 times.

 In this specification, the extrusion ratio is calculated by calculating the cross-sectional area in the extrusion direction of the polymer (4) filled in the extrusion container (1) and the internal cross-sectional area in the same direction of the die (2), and calculating the reciprocal number thereof. means. For example, if the cross-sectional area of the polymer (4) is 1 and the cross-sectional area of the die (2) is 1Z3, the extrusion ratio is 3 times.

[0026] When extrusion molding is performed by the above-mentioned hydrostatic extrusion method, it is preferable to achieve a desired extrusion ratio by one extrusion, but a plurality of extrusions are repeated to obtain a desired extrusion ratio. It may be. In addition, examples of methods for orienting such molded products include methods such as pulling, pushing, and forging.

 [0027] According to the method for manufacturing a bone treatment device of the present invention, even a composite material of a biodegradable polymer and a bioceramic has the same mechanical properties as the case of a biodegradable polymer alone. Tools can be manufactured. In particular, when the hydrostatic extrusion method is used in combination, a bone treatment device having an extremely high density and capable of maintaining an appropriate strength and rigidity during a period required for healing can be obtained.

 A bone treatment device using the method for producing a bone treatment device of the present invention is also one aspect of the present invention.

 The form of the bone treatment tool of the present invention is not particularly limited, and examples thereof include rods, plates, screws, pins, screws, staples, clips, wires, etc., obtained by processing the molded product by any method such as molding and cutting. .

 The invention's effect

 [0028] According to the present invention, there is provided a method for producing a bone treatment device made of a composite material of a biodegradable polymer and bioceramics and having excellent mechanical properties such as strength, and a bone treatment device using the production method. Can be provided.

 BEST MODE FOR CARRYING OUT THE INVENTION

[0029] Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

[0030] (Example 1)

 Hydroxyapatite fine particles (900 ° C calcined product) with an average particle size of 30 μm are immersed in a 5% by weight chloroform solution of poly_L_lactic acid (weight average molecular weight 200,000) and evaporated under reduced pressure using an evaporator. Dried. This dipping-drying process was repeated to form a poly_L_lactic acid coat layer with an adhesion amount of 12.5 wt% on the surface of the nodyl oxide fine particles.

[0031] The obtained hydroxyapatite fine particles having a coating layer and poly L lactic acid (weight average molecular weight 200,000) were put into a twin-screw extruder so that the mixing ratio of the hydroxyapatite fine particles was 30% by weight. The mixture was kneaded at a temperature of 180 ° C. and extruded to obtain pellets.

The obtained pellets are put into an injection molding machine and extruded at a temperature of 190 ° C to make a rod-shaped vial. Got.

 Once the obtained burette is cooled, it is extruded under the conditions of a temperature of 140 ° C and an extrusion speed of 0.2 mm / min using a hydrostatic extrusion apparatus shown in Fig. 1, and the extrusion rate is 4 times. A molded body was obtained. This was a pin.

 In addition, a pin having an extrusion ratio of 2.5 times by a hydrostatic extrusion method was produced by the same method, and this pin was cut and threaded to obtain a screw-shaped formed body.

[0032] (Comparative Example 1)

 Biaxial extrusion of hydroxyapatite fine particles (900 ° C calcined product) with an average particle size of 30 am and poly_L_lactic acid (weight average molecular weight 200,000) so that the mixing ratio of hydroxyapatite fine particles is 30% by weight The mixture was put into the apparatus, kneaded at a temperature of 180 ° C and extruded to obtain pellets.

 The obtained pellets were put into an injection molding machine and extruded at a temperature of 190 ° C to obtain a rod-shaped biuret.

 The obtained burette was extruded under the same conditions as in Example 1 so that the extrusion magnification was 4 times to obtain a rod-shaped molded body, which was used as a pin.

 In addition, a pin having an extrusion ratio of 2.5 times was produced by a hydrostatic extrusion method in the same manner, and this pin was cut and threaded to obtain a screw-like molded body.

[0033] (Control 1)

 Poly_L_lactic acid (weight average molecular weight 200,000) was put into a twin screw extruder, kneaded at a temperature of 180 ° C., and extruded to obtain pellets.

 The obtained pellets were put into an injection molding machine and extruded at a temperature of 190 ° C to obtain a rod-shaped biuret.

 The obtained burette was extruded under the same conditions as in Example 1 so that the extrusion magnification was 4 times to obtain a rod-shaped molded body, which was used as a pin.

 In addition, a pin having an extrusion ratio of 2.5 times was produced by a hydrostatic extrusion method in the same manner, and this pin was cut and threaded to obtain a screw-like molded body.

[0034] (Evaluation)

About the pin-shaped molded body obtained in Example 1, Comparative Example 1 and Control Example 1, JIS K 7171 The bending strength and bending energy were measured by the method according to the method, and the screw torque was measured according to the method according to JIS B 1055 for the thread-shaped formed product. The measurement was performed at n = 10, and the average value was obtained.

 The results are shown in Table 1.

 [table 1]

[0036] From Table 1, the molded body produced in Comparative Example 1 was inferior in all of the screw torque, bending strength, and bending energy compared to the pin and screw made of Poly-L-L-lactic acid alone produced in Comparative Example 1. On the other hand, the screw produced in Example 1 is slightly inferior in screw thread, but the bending strength and bending energy of the pin-shaped molded product are those of poly L monolactic acid alone. It was equal or better.

 Industrial applicability

[0037] According to the present invention, there is provided a method for producing a bone treatment tool that is made of a composite material of a biodegradable polymer and bioceramics and has excellent mechanical properties such as strength, and a bone treatment tool that uses the production method. Can be provided.

 Brief Description of Drawings

 FIG. 1 is a cross-sectional view showing the structure of an isostatic extrusion apparatus used in the present invention.

 FIG. 2 is a cross-sectional view showing another structure of the hydrostatic extrusion apparatus used in the present invention.

 FIG. 3 is a cross-sectional view showing another structure of the hydrostatic pressure extrusion apparatus according to the present invention.

 Explanation of symbols

[0039] 1 extrusion container

 2 dice

 3 extrusion ram

4 Polymer Space part Extruded side container Space part

Claims

The scope of the claims  [1] A method for producing a bone treatment device having a composite material force in which bioceramics fine particles are dispersed in a matrix made of a biodegradable polymer,  Forming a coating layer made of the biodegradable polymer on the surface of the bioceramic fine particles; and  Step 2 for preparing a kneaded product by kneading the bioceramic fine particles on which the coating layer is formed and the biodegradable polymer at a temperature equal to or higher than the melting point of the biodegradable polymer, and obtaining a molded product from the kneaded product With step 3  A method for manufacturing a bone treatment device. [2] The method for producing a bone treatment tool according to claim 1, further comprising a step of extruding the molded product under hydrostatic pressure at a temperature not lower than the melting point and not higher than the melting point of the biodegradable polymer. .  [3] The biodegradable polymer is poly (L-monolactic acid), a copolymer of L-monolactic acid and L-lactic acid mainly composed of L-monolactic acid, L-lactic acid mainly composed of L-monolactic acid and D, L-lactic acid. The method for producing a bone treatment device according to claim 1 or 2, which is a stereocomplex formed by blending poly (L) monolactic acid and poly_D_lactic acid.  [4] The method for producing a bone treatment tool according to claim 1, 2 or 3, wherein the bioceramic fine particles have a particle diameter of 1 to 100 μm.  5. The method for producing a bone treatment device according to claim 1, 2, 3 or 4, wherein the bioceramic is hydroxyapatite.  [6] A bone treatment device comprising the method for producing a bone treatment device according to claim 1, 2, 3, 4 or 5.