JP6470978B2 - Manufacturing method of biological implant - Google Patents

Description

  The present invention relates to a biological implant (artificial bone, dental implant, dental material, regenerative medical material, etc.). More specifically, the present invention relates to a biomedical implant made of resin containing PEEK, wherein at least the surface layer portion is porous and has excellent osteoconductivity.

  Conventionally, in the fields of surgery, orthopedics, and dentistry, biological implants such as artificial bones and dental implants have been used to compensate for bone defects and voids caused by diseases, accidents, and surgery. ing. From the viewpoint of early repair of a defect such as the bone, it is most important that the living body implant is bonded to the patient's own bone tissue at an early stage after the implantation.

  As a material for such a living body implant (artificial bone), a porous calcium phosphate ceramic is conventionally used together with a metal implant. This porous calcium phosphate-based ceramic grows with the introduction of new osteoblasts in the pores. Therefore, it is easy to integrate with the patient's own bone tissue, has excellent binding force, and has high osteoconductivity. Here, osteoconductivity means that it is easy to integrate with the patient's own bone tissue and that it has excellent binding power. In Patent Document 1, in an artificial bone made of a calcium phosphate-based porous ceramic, the surface roughness of a portion forming a joint surface with an autologous bone tissue is included in a specific range. The bone is listed.

  In Patent Document 2, a polymer material for artificial bone, which is a solid or gel-like body whose main component is a polysaccharide having a carboxyl group or a derivative thereof, or a polysaccharide into which a carboxyl group or a derivative thereof has been introduced, is contained in a simulated body fluid. It is described that hydroxyapatite can be produced and used as an artificial bone.

  Moreover, in patent document 3, it arrange | positions between adjacent vertebral bodies, the implant in which the opening part was formed in the exposed side exposed between vertebral bodies, and it inserts through an opening part and attaches to an implant It is described that an artificial bone made of a biocompatible material and having a specific shape can shorten the time required for joining with a new bone growing from bone tissue of a vertebral body.

  In addition to the above metal implants and calcium phosphate ceramics, materials made of resins are also used as materials for biological implants such as artificial bones and dental implants. As a material made of a thermoplastic resin, it has excellent heat resistance, fatigue resistance, wear resistance, dimensional stability, chemical resistance, and is a lightweight PEEK ( Polyetheretherketone) is used.

JP 2003-88578 A Japanese Patent No. 3359575 Japanese Patent No. 4415078

  PEEK has the following advantages as a material for living body implants. Doctors often perform image diagnosis during surgery or following the healing process, but metal implants have limitations such as the occurrence of artifacts in X-ray imaging. PEEK, on the other hand, is easy to monitor because of its high X-ray transparency. In addition, the elasticity is close to that of cortical bone as compared to metal, and depending on the size of the bone, the elasticity is higher than that of metal.

  The present inventors are currently using PEEK as a living body implant because it does not have pores and is not porous, like the above-mentioned calcium phosphate ceramics and hydroxyapatite materials, it is difficult for living bones to enter, We found that there was a problem with bone conduction ability.

  Therefore, the object of the present invention is an artificial bone having excellent heat resistance, fatigue resistance, wear resistance, dimensional stability, chemical resistance, biosafety and biocompatibility, and excellent osteoconductivity. It is to provide biological implants such as dental implants.

  Accordingly, as a result of intensive studies by the present inventors to achieve the above object, a resinous bioimplant containing PEEK, in which at least a part of the surface layer portion is formed by the porous PEEK, the porous It has been found that by setting the average pore diameter to 1 to 300 μm, biological implants such as artificial bones and dental implants excellent in osteoconductivity can be obtained, and the present invention has been completed.

  That is, the living body implant of the present invention is a resinous living body implant containing PEEK, and at least a part of the surface layer portion is formed of a porous material containing PEEK, and the average pore diameter of the porous material is 1 to 300 μm. It is characterized by that.

  In the living body implant of the present invention, the porous porosity is preferably 15 to 70%.

  In the living body implant of the present invention, it is preferable that the depth from the surface of at least the porous portion is 2 μm.

  Moreover, it is preferable that the biological implant of the present invention is subjected to a hydrophilic treatment.

  Moreover, it is preferable that the biological implant of this invention is a biological implant obtained by the manufacturing method which includes the process of forming the nonwoven fabric formed from the PEEK fiber by press molding as an essential process.

  In the living body implant of the present invention, the crystallinity of the PEEK fiber is preferably 30% or less.

  Moreover, the living body implant of the present invention is preferably an artificial bone or a dental implant.

  The living body implant of the present invention is porous at least at the surface layer portion and has a pore size of a specific size, so that new bone osteoblasts enter and grow in the pores of the surface layer portion, etc. It is easy to integrate with and has excellent bone conductivity. Moreover, since the biological implant of the present invention contains PEEK, it has excellent heat resistance, fatigue resistance, wear resistance, dimensional stability, chemical resistance, and also has biological safety and biocompatibility. It is suitable for artificial bones and dental implants.

It is the schematic which shows an example of the manufacturing method of PEEK fiber typically. It is a schematic diagram of the tailor cone formed in a belt-shaped melted part. It is sectional drawing which shows typically an example of the nonwoven fabric manufacturing apparatus containing the manufacturing method of PEEK fiber.

[Bioimplant]
The biological implant of the present invention refers to artificial bones, dental implants, dental materials, regenerative medical materials, and the like. The bio-implant is a resin-made bio-implant containing PEEK, wherein at least a part of a surface layer portion is formed of a porous material containing PEEK, and the average pore diameter of the porous material is 1 to 300 μm. To do. The average pore diameter is preferably 3 to 280 μm, more preferably 5 to 260 μm, still more preferably 10 to 240 μm, and particularly preferably 20 to 220 μm. Since the average pore diameter is in the above range, the newly formed osteoblasts are easy to enter and grow in the pores, easily integrated with the patient's own bone tissue, and have excellent osteoconductivity. The average pore diameter is measured by the method described in Examples using an electron micrograph. Note that the living body implant of the present invention differs depending on the manufacturing method of the living body implant, but the entire living body implant may be made porous, or only a part of the surface layer portion of the living body implant may be made porous. .

  The porous porosity (porosity) is preferably 15 to 70%, more preferably 20 to 65%, and further preferably 25 to 60%. When the porosity is within the above range, osteoblasts newly born in the pores are easy to grow and grow, easily integrate with the patient's own bone tissue, and have excellent osteoconductivity. The porosity is measured by the method described in Examples using an electron micrograph.

  The depth from the surface of at least the porous portion of the biological implant of the present invention is preferably 2 μm, more preferably 5 μm, and even more preferably 8 μm. When the depth from the surface of the porous portion is within the above range, the osteoblasts newly born enter the pores and grow easily, and are easily integrated with the patient's own bone tissue, and are excellent in osteoconductivity. The depth from the surface of at least the porous portion of the biological implant can be measured, for example, from an electron micrograph of a cross section of the biological implant.

  The biological implant of the present invention may contain PEEK in the porous material, and is not particularly limited. However, the amount of PEEK blended is, for example, 10% by weight or more, preferably 20% by weight or more with respect to the whole biological implant. More preferably, it is 30% by weight or more, and more preferably 50% by weight or more. Other than PEEK, other thermoplastic resins, thermosetting resins, metals, ceramics, and the like can be included within a range that does not impair the effects of the present application.

  The ratio of the porous PEEK is not particularly limited, but is, for example, 60% by weight or more, preferably 70% by weight or more, and more preferably 80% by weight or more based on the whole porous material. More preferably, it is 90% by weight or more, and it is particularly preferable that the porous material is composed only of PEEK. Other than PEEK, other thermoplastic resins, additives, and the like can be included within a range not impairing the effects of the present application.

[Method for producing biological implant]
It is preferable that the manufacturing method of the biological implant of this invention includes the process of manufacturing PEEK fiber and manufacturing the nonwoven fabric formed from PEEK fiber. Moreover, it is preferable that the manufacturing method of the biological implant of this invention includes the process (press process) of forming the nonwoven fabric formed from PEEK fiber by press molding as an essential process.

  In the pressing step, a non-woven fabric formed from PEEK fibers is used as a porous molded product in the form of a biological implant (for example, artificial bone). In the pressing step, for example, a non-woven fabric formed from PEEK fibers is bundled and compression-molded using a mold or the like, or a molded product (bioimplant such as artificial bone) already molded by another method is used. In contrast, a non-woven fabric formed from PEEK fibers is inserted into a hole provided in a molded product that has already been formed by another method, such as a method of compression molding a non-woven fabric formed from PEEK fibers by insert molding or the like. The method etc. which are united with a nonwoven fabric and set as a biological implant are mentioned. The non-woven fabric may include not only a cloth-like material but also a fiber-like material (PEEK fiber).

  The compression molding rate in the compression molding in the pressing step is preferably 0.1 to 5%, more preferably 0.3 to 3%. When the compression molding ratio is in the above range, the porosity of the porous body is likely to be 15 to 70%.

  In the method of bundling the nonwoven fabric formed from the PEEK fiber and compression-molding it using a mold or the like, for example, a porous molded product is obtained by the following method. First, a mold for a biological implant is prepared, and a non-woven fabric formed from PEEK fibers is inserted into the mold in a bundle that is thicker than the mold and compressed to a uniform thickness. Next, the mold is closed, heated, and then compression molded. Then, after cooling, the porous molded product is taken out from the mold. The heating temperature for the heating is usually about 100 to 300 ° C., and the heating time is usually about 1 to 10 minutes. The compression molding rate in compression molding is as described above. In addition, the nonwoven fabric to be inserted may include not only a cloth-like material but also a fiber-like material (PEEK fiber).

  Furthermore, the manufacturing method of the biological implant of this invention may also include the process of performing a hydrophilization process for the purpose of surface modification | reformation with respect to the porous molded article obtained by the said press process. By the hydrophilization treatment, a finer porous structure can be formed on the surface of the biological implant. Examples of the hydrophilic treatment include plasma treatment, graft reaction after plasma treatment, corona discharge treatment, glow discharge treatment, alkaline solution treatment, acid solution treatment, oxidant treatment, silane coupling treatment, anodic oxidation treatment, and rough surface. Includes processing. Of these, plasma treatment, graft reaction after plasma treatment, and corona discharge treatment are preferable.

  The plasma treatment is performed, for example, by irradiating the surface of the porous molded article obtained by the pressing step with microwave plasma in the air (air) using a microwave plasma processing apparatus. When the microwave plasma processing apparatus is a scan processing method in which the sample passes immediately below the plasma reactor at a constant speed, the feed speed is usually about 1 to 20 m / min. As the (gas) plasma, for example, oxygen, nitrogen, argon, hydrogen, or the like can be used. Further, in addition to the atmosphere (air), the process may be performed in an atmosphere such as nitrogen or argon, or may be performed in a vacuum. As the microwave plasma processing apparatus, for example, a microwave plasma processing apparatus manufactured by Nissin Co., Ltd. can be used.

  The graft reaction after the plasma treatment is performed, for example, by immersing the porous molded article after the plasma treatment in an acrylic acid such as methyl acrylate or ethyl acrylate under an atmosphere such as nitrogen or argon. Do. The surface of the porous molded product can be further modified (hydrophilized) by the graft reaction. The acrylic acid used may be a solution moderately diluted with an organic solvent such as toluene. Immersion is usually about 1 to 48 hours, may be performed at room temperature, or may be performed at a temperature of about 30 to 80 ° C.

  The corona discharge treatment is performed, for example, by irradiating the surface of the porous molded article obtained by the pressing step with corona discharge electrons that have been corona discharged in the air (air) using a corona discharge surface treatment apparatus. . When the corona discharge surface treatment apparatus is a conveyor system, the feed rate is usually about 1 to 20 m / min, and the output of the corona discharge is usually about 30 to 500 W. As the corona discharge surface treatment apparatus, for example, a corona discharge surface treatment apparatus manufactured by Wedge Corporation can be used.

Furthermore, the manufacturing method of the biological implant of the present invention includes calcium hydroxide (Ca (OH) ₂ ), calcium dihydrogen phosphate (Ca (H ₂ PO ₄ ) ₂ ), calcium chloride after the pressing step and the hydrophilization treatment. It may be immersed in an aqueous solution such as (CaCl ₂ ) and Ca ²⁺ treated. The immersion time is preferably 1 to 30 days, and more preferably 3 to 20 days. By this Ca ²⁺ treatment, it becomes easy to form apatite in the porous body of the living body implant, and it becomes easy to obtain excellent osteoconductivity.

(PEEK fiber)
The PEEK fiber is preferably a fiber having a small fiber diameter, and is not particularly limited. For example, the diameter is 10 μm or less (0.1 to 10 μm). The diameter of the PEEK fiber is preferably 0.5 to 8 μm, more preferably 0.7 to 6 μm. Moreover, the fiber which has a fiber diameter (diameter) of about 50-1000 nm may be contained in the fiber which has such a diameter, for example. The diameter of the PEEK fiber can be adjusted by appropriately adjusting various conditions (for example, the thickness of the polymer sheet, the feeding speed of the polymer sheet, and the laser intensity) of the PEEK fiber manufacturing method described later. The diameter of the PEEK fiber can be measured using, for example, an electron microscope.

  The average fiber diameter (average diameter) as the PEEK fiber aggregate is preferably 10 μm or less (0.1 to 10 μm), more preferably 0.5 to 8 μm, and still more preferably 0.7 to 6 μm. The average fiber diameter is obtained by, for example, photographing a plurality of (for example, 10) fiber forms using a scanning electron microscope, and arbitrarily processing the diameter of about 10 fibers per image from the photographed images. It can be obtained by measuring with and averaging them.

  The PEEK fiber preferably has a crystallinity of 30% or less, more preferably 29% or less, and still more preferably 28% or less. When the crystallinity is 30% or less, the processability is excellent and the nonwoven fabric can be easily formed. The crystallinity can be determined by, for example, an X-ray diffraction method, DSC (differential scanning calorimeter) measurement, density method, or the like. In the present application, the degree of crystallinity was calculated from the amount of heat obtained from DSC measurement by the method described in Examples.

  The ratio of PEEK in the PEEK fiber is not particularly limited, but is, for example, 60% by weight or more, preferably 70% by weight or more, and more preferably 80% by weight or more based on the whole PEEK fiber. More preferably, it is 90% by weight or more, and it is particularly preferable that the PEEK fiber is composed only of PEEK. Other than PEEK, other thermoplastic resins and additives can be included. Moreover, it is preferable that the said PEEK fiber is obtained by the manufacturing method of the PEEK fiber mentioned later using a polymer sheet as a raw material.

  The polymer sheet preferably has a crystallinity of 25% or less, more preferably 20% or less, and even more preferably 15% or less. When the crystallinity is 25% or less, a PEEK fiber having a low crystallinity can be obtained. The crystallinity of the polymer sheet can be determined by the same method as the crystallinity of the PEEK fiber.

  The polymer sheet preferably has a low melt viscosity from the viewpoint of easily obtaining a fiber having a small fiber diameter. For example, the polymer sheet is melted at a shear rate (shear rate) of 121.6 (1 / s) measured at 400 ° C. The viscosity is preferably 800 Pa · s or less (50 to 800 Pa · s), more preferably 600 Pa · s or less, and still more preferably 400 Pa · s or less. The melt viscosity can be determined by a capillary rheometer (trade name “Capillograph 1D”, manufactured by Toyo Seiki Seisakusho Co., Ltd.) according to the method described in Examples. The shear rate (shear rate) can also be measured using a capillary rheometer.

  The polymer sheet can be produced by, for example, heating and melting chip-like PEEK with a T-die extruder or the like to form a sheet. A commercially available product can be used as the chip-like PEEK, and a trade name “VESTAKEEP 1000G” (manufactured by Daicel-Evonik Co., Ltd.) can be preferably used. In addition, the heating temperature of a T-die extrusion molding machine should just be more than melting | fusing point of PEEK, for example, is 350-400 degreeC.

  The polymer sheet includes various additives used for fibers, such as infrared absorbers, stabilizers (antioxidants, ultraviolet absorbers, heat stabilizers, etc.), flame retardants, antistatic agents, colorants, fillers. , Lubricants, antibacterial agents, insect and acaricides, fungicides, matting agents, heat storage agents, fragrances, fluorescent brighteners, wetting agents, plasticizers, thickeners, dispersants, foaming agents, surfactants, etc. You may contain. These additives can be blended alone or in combination of two or more.

  Of these additives, a surfactant is preferably used. When a charge is injected by applying a high voltage to the polymer sheet, the polymer sheet has high electrical insulation, and it is difficult to inject the charge to the heat melting portion where the electrical resistance is low. However, when a surfactant is used, the electric resistance of the surface of the polymer sheet having a large electrical insulation is lowered, and charges can be sufficiently injected up to the heat melting portion. Also, the application of a surfactant or the like is effective for phase separation when the sheet is composed of a plurality of components when a high voltage is applied to the polymer sheet to inject charges.

  Each of these additives can be used at a ratio of 50 parts by weight or less, preferably 0.01 to 30 parts by weight, more preferably 0.1 to 5 parts, per 100 parts by weight of the resin constituting the polymer sheet. It is the ratio of parts by weight.

  The thickness of the polymer sheet is preferably 0.01 to 10 mm, more preferably 0.05 to 5.0 mm. When the thickness is in the above range, the PEEK fiber described later can be easily manufactured.

The nonwoven fabric is obtained by accumulating the PEEK fibers in a cloth shape. What is necessary is just to select the thickness of the said nonwoven fabric suitably according to a use, Although it can select from the range of about 0.0001-100mm, Preferably it is 0.001-50mm, More preferably, it is 0.01-15mm, More preferably 0.05-1 mm. Further, the basis weight of the nonwoven fabric can be selected according to the intended use, preferably from 0.001 to 100 g / m ^2, more preferably 0.05 to 50 g / m ^2, more preferably 0.1 to 10 g / m ² . In the nonwoven fabric manufacturing method described later, the nonwoven fabric is controlled in the fiber diameter, thickness, basis weight, and other shapes of the nonwoven fabric to be manufactured by adjusting the sheet feed rate and laser strength, and the moving speed of the collecting member. can do.

(PEEK fiber manufacturing method)
The PEEK fiber is not particularly limited, but is preferably produced using a laser melting electrospinning method described later. Specifically, the laser melting electrospinning method is the following method.

  A method for producing the PEEK fiber (laser melting electrospinning method) will be described with reference to the drawings. FIG. 1 is a schematic view schematically showing an example of a method for producing PEEK fiber. In the PEEK fiber manufacturing method, the polymer sheet is irradiated with a band-shaped laser beam to heat and melt the end of the polymer sheet in a linear shape, and a potential difference is generated between the melted band-shaped melted part and the fiber collecting plate. By forming a needle-like protrusion in the belt-like melted portion, and causing the fibers discharged from the needle-like protrusion to fly in the fiber collecting plate direction, the fiber collecting plate or the belt-like molten portion And PEEK fiber is obtained by collecting on a collecting member interposed between the fiber collecting plates.

  In the PEEK fiber manufacturing method, as shown in FIG. 1, a laser beam having a spot-like cross section emitted from a laser generating source 1 is converted into an optical path adjusting means comprising a beam expander and homogenizer 2, a collimation lens 3 and a cylindrical lens group 4. After being converted into a strip-shaped laser beam 5 having a linear cross section through the film, the strip-shaped melted portion 6a formed at the end of the polymer sheet 6 held by the holding member 7 is irradiated with the high-voltage generator 10 A voltage is applied to generate a potential difference between the belt-shaped melted part 6a and the fiber collecting plate 8 disposed below the polymer sheet 6. Further, the temperature of the belt-shaped melted portion 6a can be observed by the thermography 9, and the conditions such as the voltage and the laser beam to be irradiated can be optimized.

  In the example shown in FIG. 1, the holding member 7 that holds the polymer sheet 6 also functions as an electrode. When a voltage is applied to the holding member 7 by the high-voltage generator 10, the polymer sheet 6 Charge is applied to the band-shaped melted portion 6 a formed by the irradiation of the band-shaped laser beam 5. The fiber collecting plate 8 has a surface electrical resistance value comparable to that of a metal. Examples of the shape include a plate shape, a roller shape, a belt shape, a net shape, a saw shape, a wave shape, a needle shape, and a line shape. The optical path adjusting means is an assembly of optical components, and includes a beam expander and homogenizer 2, a collimation lens 3, a cylindrical lens group 4, and the like. By using these optical path adjusting means, the spot laser beam can be converted into the band laser beam 5.

  In the example shown in FIG. 1, the irradiation with the band-shaped laser beam 5 heats and melts the band-shaped melted portion 6 a of the polymer sheet 6, and charges are added to the heat-melted portion. As shown in FIG. 2, in the belt-like melted portion 6a to which electric charges are applied, charges are collected and repelled on the surface, thereby gradually forming a plurality of needle-like protrusions (tailor cones) 6b. When the force exceeds the surface tension, the molten polymer sheet is discharged as fibers from the tip of the tailor cone to the fiber collecting plate 8 by electrostatic attraction, that is, fibers are formed from the needle-like protrusions 6b. Fly in the direction of the collection plate 8. As a result, the elongated fibers are collected by the fiber collecting plate 8. Further, when a collecting member is placed on the fiber collecting plate 8, the fibers are collected on the collecting member. That is, in the PEEK fiber manufacturing method, the fiber collection plate itself may be a member for collecting fibers, or the collection member may be placed on the fiber collection plate separately from the fiber collection plate. is there. FIG. 2 is a schematic view of a tailor cone formed in the belt-shaped melted portion 6a.

  The number of tailor cones shown in FIG. 2 (tailor cone spacing) can be adjusted by appropriately changing the thickness of the polymer sheet 6. The development of the tailor cone means that the height of the tailor cone (h in FIG. 2) increases.

  The number of tailor cones is not particularly limited, but is preferably 1 to 100, more preferably 1 to 50, and still more preferably per 2 cm in the width direction of the heated and melted portion of the polymer sheet. 2 to 10 pieces. If the number of tailor cones is 1 to 100 per 2 cm in the width direction, the fiber leveling will not be reduced due to electrical repulsion between tailor cones, and an appropriate production amount can be secured. it can.

Examples of the laser generation source include a YAG laser, a carbon dioxide (CO ₂ ) laser, an argon laser, an excimer laser, and a helium-cadmium laser. Of these, a carbon dioxide laser is preferred because of its high power efficiency and high PEEK meltability. The wavelength of the laser beam is preferably 200 nm to 20 μm, more preferably 500 nm to 18 μm, and still more preferably 5 to 15 μm.

  Moreover, in the manufacturing method of the said PEEK fiber, when irradiating a strip | belt-shaped laser beam, the thickness of the laser beam becomes like this. Preferably it is 0.5-10 mm. If the thickness of the laser beam is less than 0.5 mm, it may be difficult to form a tailor cone. If the thickness is more than 10 mm, the melt residence time becomes long and the material may be deteriorated.

  The laser beam output may be controlled so that the temperature of the belt-shaped melted portion is not lower than the melting point of the polymer sheet and not higher than the ignition point of the polymer sheet. From the standpoint of reducing the diameter, a higher value is preferable. The specific output of the laser beam can be appropriately selected according to the physical properties (melting point, LOI value (limit oxygen index)) and shape of the polymer sheet to be used, the feeding speed of the polymer sheet, etc., but preferably 5 to 100 W. / 13 cm, more preferably 20 to 60 W / 13 cm, and still more preferably 30 to 50 W / 13 cm. The output of the laser beam is an output of a spot beam emitted from a laser generation source.

  The temperature of the belt-like melted portion is not particularly limited as long as it is not lower than the melting point (334 ° C.) of PEEK and not higher than the ignition point, but is usually about 300 to 600 ° C., preferably 350 to 500 ° C. .

  In the method of manufacturing the PEEK fiber shown in FIG. 1, the laser beam is applied to the belt-shaped melted portion (end portion) of the polymer sheet from only one direction. For example, the laser beam is applied from two directions via a reflection mirror. You may irradiate the strip | belt-shaped fusion | melting part (edge part) of a polymer sheet. This is because even if the thickness of the polymer sheet is large, the end portion thereof can be melted more uniformly.

  In the PEEK fiber manufacturing method, the potential difference generated between the end of the polymer sheet and the collecting member is preferably a high voltage within a range where no discharge occurs, and the required fiber diameter (diameter), electrode Although it can select suitably according to the distance with a collection member, the irradiation amount of a laser beam, etc., it is about 0.1-30 kV / cm normally, Preferably it is 0.5-20 kV / cm, More preferably, it is 1-. 10 kV / cm.

  The method of applying a voltage to the melted part of the polymer sheet may be a direct application method in which the laser light irradiation part (the belt-like melted part of the polymer sheet) and the electrode part for applying electric charge are matched. The laser beam irradiation part and the charge are given from the point that the device can be easily manufactured, the laser beam can be effectively converted into thermal energy, the reflection direction of the laser beam can be easily controlled, and the safety is high. An indirect application method (particularly, a method of providing a laser beam irradiation part on the downstream side in the feeding direction of the polymer sheet) is preferred in which the electrode part is provided at a separate position. In particular, in the above manufacturing method, the polymer sheet is irradiated with a band-shaped laser beam on the downstream side of the electrode unit, and the distance between the electrode unit and the laser beam irradiation unit (for example, the lower end of the electrode unit and the upper side of the band-shaped laser beam) It is preferable to adjust the distance to the outer edge to a specific range (for example, about 10 mm or less). This distance can be selected according to the electrical conductivity, thermal conductivity, glass transition point, laser beam irradiation amount, etc. of the polymer sheet, preferably 0.5 to 10 mm, more preferably 1 to 8 mm, and still more preferably 1. .About.5 to 7 mm, particularly preferably about 2 to 5 mm. When the distance between the two is in this range, the molecular mobility of the resin in the vicinity of the laser light irradiation portion is increased, and a sufficient charge can be imparted to the molten resin, so that productivity can be improved.

  In addition, the distance between the end of the polymer sheet (the tip of the tailor cone) and the collecting member is not particularly limited, and is usually 5 mm or more, but for efficiently producing a fiber having a small diameter. Is preferably 10 to 300 mm, more preferably 15 to 200 mm, still more preferably 50 to 150 mm, and particularly preferably 80 to 120 mm.

  When the polymer sheet is continuously fed out, the feeding speed is not particularly limited, but is preferably 2 to 20 mm / min, more preferably 3 to 15 mm / min, and further preferably 4 to 10 mm / min. is there. Increasing the speed increases the productivity, but if the speed is too high, the polymer sheet in the vicinity of the laser light irradiation part does not melt sufficiently, so that it is difficult to manufacture the fiber. On the other hand, when the speed is low, the polymer sheet is decomposed or the productivity is lowered.

  Moreover, in the said manufacturing method, an inert gas atmosphere may be sufficient as the space between the edge part of the said polymer sheet and the said collection member. By making this space an inert gas atmosphere, the firing of the fibers can be suppressed, so that the output of the laser light can be increased. Examples of the inert gas include nitrogen gas, helium gas, argon gas, carbon dioxide gas, and the like. Of these, nitrogen gas is usually used. In addition, the use of the inert gas can suppress the oxidation reaction in the belt-like melted portion.

  The space may be heated. Thereby, the diameter of the obtained fiber can be made small. That is, by heating the air or inert gas in the space, it is possible to suppress a rapid temperature drop of the fiber being formed, thereby promoting the elongation or stretching of the fiber and obtaining a finer fiber. It is done. Examples of the heating method include a method using a heater (such as a halogen heater) and a method of irradiating a laser beam. The heating temperature can be selected from, for example, a temperature range from 50 ° C. or higher to less than the ignition point of the resin, but from the viewpoint of spinnability, a temperature lower than the melting point of PEEK is preferable.

(Method for producing non-woven fabric formed from PEEK fiber)
Next, an example of a method for producing a nonwoven fabric formed from PEEK fibers will be described. In the manufacturing method of the nonwoven fabric formed from the following PEEK fiber, in the above-mentioned manufacturing method of PEEK fiber, the manufacturing position of the PEEK fiber is moved while moving the collection position of the fibers flying in the fiber collecting plate direction. The method is continuously performed, and these are accumulated in a cloth shape to obtain a nonwoven fabric. The nonwoven fabric formed from PEEK fiber may be manufactured by the method shown below, and the PEEK fiber obtained by the manufacturing method of the PEEK fiber may be converted into a nonwoven fabric by another method.

  Here, as a method for moving the collection position of the fibers flying in the fiber collection plate direction with time, for example, (1) a collection member (when the fiber collection plate itself functions as a collection member) (2) a method of moving the holding position of the polymer sheet, (3) a mechanical, magnetic or electrical force on the flying fiber from the tailor cone toward the collecting member. For example, a method of applying a strong force, for example, a method of blowing air to a fiber in flight, (4) a method of selectively combining the methods (1) to (3), and the like can be used.

  Among these, the method of (1) above, that is, the method of moving the collecting member is easy in that the configuration of the apparatus is easy and the shape (thickness, basis weight, etc.) of the nonwoven fabric to be manufactured can be easily controlled. desirable. Hereinafter, the method for producing a non-woven fabric formed from PEEK fibers will be described in detail by taking the case of using the method (1) as an example.

  In the manufacturing method of the nonwoven fabric formed from the PEEK fiber using the method of (1) above, in the PEEK fiber manufacturing method shown in FIG. 1, a collecting member is placed on the fiber collecting plate 8. The PEEK fiber manufacturing method is continuously performed while moving the collecting member in a direction perpendicular to the width method of the polymer sheet 6 (right direction or left direction in the figure). Here, the moving speed of the collecting member may be constant, may change with time, and may be repeatedly moved and stopped. In order to continuously perform the PEEK fiber manufacturing method, as described above, the polymer sheet 6 is moved to the fiber collecting plate 8 side (collecting member side) as the fiber manufacturing process proceeds. What is necessary is just to send out continuously. In addition, the speed | rate (feed speed) which sends out a polymer sheet continuously is as having described with the manufacturing method of the said PEEK fiber.

Moreover, the moving speed of the collecting member on the fiber collecting plate 8 is not particularly limited, and may be appropriately determined in consideration of the basis weight of the fiber sheet to be manufactured, but is usually about 10 to 2000 mm / min. For example, when the feeding speed of the polymer sheet having a basis weight of 1000 g / m ² is 0.5 mm / min, by setting the moving speed of the collecting member to about 1000 mm / min, the basis weight is about 0.5 g / m ² . Nonwoven fabrics can be produced continuously.

  FIG. 3 is a cross-sectional view schematically showing an example of a nonwoven fabric manufacturing apparatus including the method of manufacturing the PEEK fiber shown in FIG. The apparatus (nonwoven fabric manufacturing apparatus) shown in FIG. 3 has a laser source 11, an optical path adjusting member 12, a polymer sheet feeding device 13 that can continuously feed the polymer sheet 6, and a holding that holds the polymer sheet 6. The member 16, the electrode 17 for applying charge to the polymer sheet 6, the collecting member 22 for collecting fibers, the belt 17 and the belt-like melted part (end part) 6 a of the polymer sheet 6, and the collecting member 22 The high-voltage generators 20a and 20b for applying voltages to the fiber collecting plate 14 and the housing 23 in which the heating device 15 is disposed, the electrode 17 and the fiber collecting plate 14, respectively. A pulley 21 for moving the collecting member 22 is provided. The optical path adjusting member 12 is an assembly of optical components as described above, and includes the beam expander and homogenizer 2, the collimation lens 3, and the cylindrical lens group 4 shown in FIG.

  In FIG. 3, the belt-shaped laser light 5 emitted from the laser generation source 11 and passed through the optical path adjusting member 12 is introduced into the housing 23 and irradiated to the belt-shaped melted portion (end portion) 6 a of the polymer sheet 6. . A polymer sheet feeding device 13 having a motor and a mechanism for converting the rotational motion of the motor into a linear motion is attached to the upper portion of the housing 23. The polymer sheet 6 is attached to the polymer sheet feeding device 13. And are continuously fed into the housing 23. On the other hand, the lower part of the polymer sheet 6 is held by a holding member 16 to which an electrode 17 is attached. Since the polymer sheet 6 and the electrode 17 are always in contact with each other, a charge is applied to the polymer sheet 6 when a voltage is applied to the electrode 17.

  The fiber collecting plate 14 that functions as a pair with the electrode 17 (functions as an electrode that forms a pair with the electrode 17) is located at a position facing the polymer sheet 6 through the belt-shaped melted portion (end portion) 6 a and the collecting member 22. It is arranged. Therefore, when a voltage is applied to the electrode 17 and the fiber collecting plate 14, a potential difference is generated between the belt-shaped melted portion (end portion) 6 a of the polymer sheet 6 and the collecting member 22. The application of voltage to the electrode 17 and the fiber collecting plate 14 is performed by the high voltage generators 20a and 20b connected thereto. In this nonwoven fabric manufacturing apparatus, the electrode 17 is a positive electrode and the fiber collecting plate 14 is a negative electrode. The collecting member 22 is a belt conveyor including a pulley 21 and a conveyor belt, and the conveyor belt itself corresponds to the collecting member 22. Therefore, as the pulley 21 is driven, the collecting member 22 (conveyor belt) moves in a predetermined direction (for example, rightward in the figure).

  The nonwoven fabric manufacturing apparatus shown in FIG. 3 includes a heating device 15, and can heat the stretched fibers that are discharged from the belt-shaped melted portion (end portion) 6 a of the polymer sheet 6 toward the collecting member 22. . Further, a laser light absorbing plate 19 and a heat absorbing plate 18 are provided in the housing 23.

  In the nonwoven fabric manufacturing apparatus shown in FIG. 3, the polymer sheet 6 is fed while the polymer sheet 6 is fed by the polymer sheet feeding device 13 and the holding member 16 in a state where a voltage is applied to both the electrode 17 and the fiber collecting plate 14. By irradiating the belt-like melted portion (end portion) 6a with the belt-like laser beam 5, a tailor cone is formed on the belt-like melted portion (end portion) 6a of the polymer sheet 6 as described above. The fibers are discharged and fly to the fiber collecting plate 14, and as a result, the elongated fibers are collected by the collecting member 22. And the nonwoven fabric can be manufactured on the collection member 22 by moving the collection member 22 while feeding the polymer sheet 6 continuously (discharging fiber continuously).

  In the nonwoven fabric manufacturing apparatus shown in FIG. 3, the collection member 22 is a sheet-like member. In this apparatus, the collecting member 22 is not particularly limited as long as it is in the form of a sheet, but is paper, film, various woven fabrics, non-woven fabric, mesh or the like. Further, the collecting member may be a metal or a sheet or a belt having a surface electrical resistance value equivalent to that of a metal.

  In the nonwoven fabric manufacturing apparatus shown in FIG. 3, the electrode 17 and the fiber collecting plate 14 may be made of a conductive material (usually a metal component). For example, a Group 6 element such as chromium or a 10th element such as platinum. Group metals, Group 11 elements such as copper and silver, Group 12 elements such as zinc, Group 13 elements such as aluminum, simple metals and alloys (aluminum alloys, stainless steel alloys, etc.), or compounds containing these metals (Metal oxides such as silver oxide and aluminum oxide) and the like. These metal components can be used alone or in combination of two or more. Of these metal components, copper, silver, aluminum, stainless steel alloy and the like are particularly preferable. The shape of the fiber collecting plate 14 is not particularly limited, and examples thereof include a plate shape, a roller shape, a belt shape, a net shape, a saw shape, a wave shape, a needle shape, and a line shape. Of these shapes, a plate shape and a roller shape are particularly preferable. Examples of the laser light absorbing plate 19 include a metal coated with a black body and a porous ceramic. Examples of the heat absorbing plate 18 include black ceramic. By using such an apparatus, the nonwoven fabric can be produced efficiently.

  Hereinafter, the present invention will be described in more detail based on examples, but the present invention is not limited to these examples.

(Production of polymer sheet)
A chip sample of PEEK [manufactured by Daicel-Evonik Co., Ltd., trade name “VESTAKEEP 1000G”] is manufactured with a lab plast mill T die extrusion apparatus (manufactured by Toyo Seiki Seisakusho Co., Ltd.) with a die width of 150 mm and a lip width of 0.4 mm. A T-die is used to extrude into a sheet at an extrusion temperature of 345 to 360 ° C., and is taken up at a take-up roll temperature of 140 ° C. and a winding speed of 1.0 to 2.0 m / min. Was made.
The produced polymer sheet had a melt viscosity (400 ° C.) measured by the following method of 151 Pa · s, and the polymer sheet had a crystallinity of 12.7%. The crystallinity of the polymer sheet was determined by the same method as the crystallinity of the PEEK fiber forming the following nonwoven fabric.

(Measurement method of melt viscosity (400 ° C) of polymer sheet)
The melt viscosity at a shear rate (shear rate) of 121.6 (1 / s) measured at 400 ° C. of the polymer sheet was measured with a capillary rheometer (trade name “Capillograph 1D”, manufactured by Toyo Seiki Seisakusho Co., Ltd.) The measurement was performed using a jig having a capillary diameter of 1 mm and a length of 10 mm.

  Next, the nonwoven fabric formed from PEEK fiber was manufactured with the following method using the polymer sheet produced by said method.

(Manufacture of non-woven fabric formed from PEEK fiber)
The nonwoven fabric formed from PEEK fiber was manufactured with the nonwoven fabric manufacturing apparatus shown in FIG.
As the laser source 11 of the apparatus shown in FIG. 3, a CO ₂ laser (Universal Laser Systems, wavelength 10.6 μm, output 45 W, air-cooled type, beam diameter φ4 mm) was used. As the optical path adjusting member 12 of the apparatus shown in FIG. 3, a beam expander with a magnification of 2.5 times, a homogenizer (incident beam diameter φ12 mm (design value), output beam diameter φ12 mm (design value)), and a collimation lens (incident A beam diameter φ12 mm (design value), an outgoing beam diameter φ12 mm (design value), a cylindrical lens (plano-concave lens, f-30 mm), and a cylindrical lens (plano-convex lens, f-300 mm) are arranged at predetermined positions in this order. We used what we did. By passing through these optical path adjusting members, the spot-shaped laser beam is converted into a band-shaped laser beam 5 having a width of about 150 mm and a thickness of about 1.4 mm, and irradiated to the band-shaped melted portion (end) 6a of the polymer sheet 6. did. At this time, the output of the laser beam was 61 W / 13 cm, the feeding speed of the polymer sheet was 6 mm / min, and the potential difference between the electrode 17 and the fiber collecting plate 14 was 6 kV / cm.
Thereby, the nonwoven fabric formed from the PEEK fiber whose fiber diameter (diameter) is 0.7 micrometer was obtained. The degree of crystallinity of the PEEK fiber forming the nonwoven fabric by the following measurement method was 24.0%.

(Measurement method of crystallinity of PEEK fiber forming nonwoven fabric)
The degree of crystallinity of the PEEK fiber forming the nonwoven fabric was calculated from the amount of heat obtained from DSC measurement.
DSC measurement is performed using a differential scanning calorimeter (DSC-Q2000 / TA), using alumina as a reference material, under a nitrogen atmosphere, in a temperature range of 0 to 420 ° C., and at a rate of temperature increase of 20 ° C./min. It was.
The crystallinity was determined from the amount of heat determined by DSC measurement using the following formula.
Crystallinity (%) = {(heat of fusion of sample [J / g]) − (heat of recrystallization of sample [J / g])} / heat of fusion of complete crystal (130 [J / g]) × 100

Example 1
The nonwoven fabric formed from the PEEK fiber obtained by the above method was inserted into a mold (width 10 mm, length 30 mm, thickness 1 mm) in a bundle so that the thickness after molding was 1 mm, and after closing the mold, 200 ° C. Was heated for 5 minutes and pressed (compression molding) to obtain a porous molded product. The obtained porous molded product was subjected to plasma treatment (surface modification treatment) to obtain a biological implant (artificial bone material). The plasma treatment was performed at a feed rate of 3 m / min using a nitrogen plasma as a gas plasma after evacuation using a microwave plasma treatment apparatus manufactured by Nissin Co., Ltd.

Example 2
A porous molded product was obtained by pressing (compression molding) in the same manner as in Example 1. The obtained porous molded article was subjected to corona treatment (surface modification treatment) in air to obtain a biological implant (artificial bone material). The corona treatment was performed using a corona discharge surface treatment apparatus manufactured by Wedge Corporation at a corona discharge output of 200 W and a feed rate of 3 m / min.

Example 3
A porous molded product was obtained by pressing (compression molding) in the same manner as in Example 1. The obtained porous molded article was subjected to plasma treatment (surface modification treatment) and then grafted with methyl acrylate. Thereafter, a 1 mol / l aqueous solution of calcium hydroxide (Ca (OH) ₂ ) was allowed to act at 60 ° C. for 6 hours to obtain a biological implant (artificial bone material). The plasma treatment was performed at a feed rate of 3 m / min using a nitrogen plasma as a gas plasma after evacuation using a microwave plasma treatment apparatus manufactured by Nissin Co., Ltd. Grafting was effected in a 30% methyl acrylate-toluene solution at 60 ° C. for 12 hours under an argon atmosphere.

Example 4
A porous molded article (biological implant) was obtained by pressing (compression molding) in the same manner as in Example 1. The obtained porous molded article is subjected to plasma treatment (surface modification treatment), and then 0.3 mmol / l calcium dihydrogen phosphate (Ca (H ₂ PO ₄ ) ₂ ) and 0.7 mmol / l chloride. An aqueous solution mixed with calcium (CaCl ₂ ) was allowed to act at 60 ° C. for 6 hours to obtain a biological implant (artificial bone material). The plasma treatment was performed at a feed rate of 3 m / min using a nitrogen plasma as a gas plasma after evacuation using a microwave plasma treatment apparatus manufactured by Nissin Co., Ltd.

Comparative Example 1
The produced polymer film was used as it was, and a sample obtained by subjecting the surface of the polymer film to plasma treatment was used as a sample. The plasma treatment was performed at a feed rate of 3 m / min using a nitrogen plasma as a gas plasma after evacuation using a microwave plasma treatment apparatus manufactured by Nissin Co., Ltd.

(Evaluation method of biological implants (artificial bone materials))
After the biological implants (artificial bone materials) of Examples 1 to 4 and Comparative Example 1 were immersed in simulated body fluid (SBS) at 36.5 ° C. for 1 week, the formation of apatite was observed visually and by an electron microscope (SEM). ) By observing changes in the surface shape. When the formation of apatite was confirmed (◯; bone conduction ability was good), and when the formation of apatite was not confirmed (x; bone conduction ability was bad). Simulated body fluid (SBS) Am. Ceram. Soc. , 78, 1769-1774 (1995).

(Measurement of porous average pore diameter)
About the living body implant (artificial bone material) of Examples 1 to 4 and Comparative Example 1 above, the cross section of the porous portion of the living body implant is cut out, and the area of any 30 or more pores from the electron micrograph of the section And the average value was defined as the average pore area _Save . Assuming that the pores are perfect circles, the value obtained by converting the average pore area into the pore diameter using the following formula was defined as the average pore diameter. Here, π represents a circumference ratio.
Average pore diameter [μm] = 2 · (S _ave / π) ^1/2

(Measurement of porous porosity)
About the biological implant (material for artificial bone) of said Examples 1-4 and the comparative example 1, the porous porosity of the biological implant was computed from the following formula.
A part or all of the surface layer portion of the biological implant was cut out, and the volume and weight thereof were measured.
In the following formula, V represents the volume (cm ³ ) of the porous (surface layer part) of the biological implant, W represents the weight (g) of the porous of the biological implant, and ρ represents the density [g / cm ³ ]. The density of PEEK was 1.27 [g / cm ³ ].
Porosity [%] = 100-100 · W / (ρ · V)

DESCRIPTION OF SYMBOLS 1 Laser generating source 2 Beam expander and homogenizer 3 Collimation lens 4 Cylindrical lens group 5 Band-shaped laser beam 6 Polymer sheet 6a Band-shaped melting part 6b Needle-shaped protrusion part 7 Holding member 8 Fiber collection board 9 Thermography 10 High voltage generator 11 Laser generating source 12 Optical path adjusting member 13 Polymer sheet feeding device 14 Fiber collecting plate 15 Heating device 16 Holding member 17 Electrode 18 Heat absorbing plate 19 Laser light absorbing plate 20a High voltage generating device 20b High voltage generating device 21 Pulley 22 Collecting Member 23 Case h Tailor cone height w Width direction

Claims (5)

A process of obtaining PEEK fibers having an average fiber diameter of 0.1 to 10 μm by laser melting electrospinning and obtaining a nonwoven fabric formed from PEEK fibers, and pressing the nonwoven fabric to form a porous molded article in the form of a biological implant A method for producing a biological implant, comprising the steps of obtaining, and a step of hydrophilizing the porous molded article, as essential steps.
A method for producing a living body implant, wherein a living body implant having at least a part of a surface layer portion of the living body implant formed of a porous material containing PEEK and having an average pore diameter of 1 to 300 μm is obtained.   The method for producing a living body implant according to claim 1, wherein the porosity of the porous body of the living body implant is 15 to 70%.   The method for producing a biological implant according to claim 1 or 2, wherein the depth from the surface of the porous portion of the biological implant is at least 2 µm.   The method for producing a biological implant according to any one of claims 1 to 3, wherein the crystallinity of the PEEK fiber is 30% or less.   The method for producing a biological implant according to any one of claims 1 to 4, wherein the biological implant is an artificial bone or a dental implant.

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