JP5077935B2 - Method for producing highly interconnected porous body - Google Patents

Description

  The present invention relates to a method for producing a porous body having high connectivity as compared with a porosity for holding a filter substrate and cells and tissues.

A method for obtaining a porous body by mixing a water-soluble pore source with a resin and immersing it in water is a method using water-soluble inorganic compound particles such as sodium chloride, water-soluble organic polymers such as oligosaccharides and sugar as the pore source. However, since the pore source has a nearly spherical shape, the volume ratio of the pore source needs to be 50% or more as seen in, for example, JP-A-6-184349. As a result, the strength of the porous body obtained with an increase in porosity was greatly reduced. On the other hand, in JP-A-5-96640, an alcohol-soluble resin molded into a spherical or fibrous shape as a pore source is placed in a mold, the end of the resin is brought into contact with the mold and fixed, and then a resin that forms a porous body is injection molded and then polymerized However, in this method, if the viscosity of the resin injected into the mold is not low, the fibrous pore source will be destroyed and the continuous ventilation holes will be destroyed. Application to is difficult.
In addition, a method of obtaining a porous ceramic body by mixing beads and fibers made of organic polymer into ceramic slurry or ceramic powder and firing the mixture is widely known. Swells and cracks enter the pore walls made of ceramics due to the gas that is expanded and generated during combustion. Thereby, the strength of the porous body is greatly reduced. In order to solve this problem, the slurry is foamed and fixed after the foam is fixed, as in Patent No. 3400740, Patent No. 3470759, Patent No. 3718708, Patent No. 3887085, Patent No. 3897220, and sintered. There are known a method and a method of sintering after removing ice crystals by utilizing the growth of ice crystals, as in Japanese Patent No. 3940770. However, in the former, since the pore communicating portion is smaller than the pore main body, the effective sectional area as the communicating hole is smaller than the pore diameter. In the latter case, it is possible to create a porous body communicating with one axis, but it is relatively difficult to control the pore diameter and the porosity.
JP-A-6-184349 JP 5-96640

  In view of such circumstances, the present invention aims to provide a method for producing a porous body that is surely communicated even with a low porosity and that is obtained as the pore shape is as expected. And

The method for producing a highly interconnected porous body according to the first aspect of the present invention is a method for producing a porous body having a porosity of 28% or more and having pores communicating between the upper surface and the lower surface. A step of forming a composite in which water-soluble polymer fibers are mixed in a water-insoluble material by molding by heat-compression after heat-kneading, and the composite is mixed with water or a water-containing solvent ( phosphorus) phosphate buffered saline, physiological saline, and immersed in comprising an aqueous solution containing one of ions selected from the group of seawater or fluid), before eluting the only Kisui soluble polymer fiber porous And a step of performing .

  Invention 2 is a method for producing a highly interconnected porous body according to Invention 1, wherein the water-insoluble material is a matrix made of a biocompatible material.

  Invention 3 is a method for producing a highly interconnected porous body according to Invention 1, wherein the water-insoluble material is a matrix containing ceramics.

Invention 4 is a method for producing a highly interconnected porous body according to Invention 3 , wherein only the water-soluble polymer fiber is eluted from the water-insoluble material comprising the ceramic-containing matrix, and then the water-insoluble material is sintered. Thus, a ceramic porous body is obtained.

A fifth aspect of the present invention is the method for producing a highly interconnected porous body according to the fourth aspect, wherein the ceramic is a biocompatible ceramic.

According to the present invention, a fiber made of a water-soluble polymer is eluted in an aqueous solution or a similar polar solvent to become a porous body made of a water-insoluble material. By using a fibrous pore source and uniformly mixing it with a water-insoluble material, a material having high connectivity can be obtained from a low porosity range.
At this time, the water-insoluble material may be an adhesive or an epoxy resin, and water-soluble fibers may be dispersed therein to form a repair material such as a defective portion of a material that requires pores such as a filter of a polar solvent it can. That is, an adhesive or an epoxy resin in which water-soluble fibers are dispersed is filled in a portion to be repaired, and water or the like is eluted by passing water through the repair portion after the adhesive or resin is cured. Therefore, repair can be performed while maintaining the porosity after repair.
Moreover, the porous body for biological bodies can be obtained by making the said water-insoluble material into a biocompatible material. At this time, if the water-soluble fiber is a biocompatible material, a material can be obtained in which the water-soluble fiber is rapidly eluted in the living body and the pores are rapidly formed in the living body. By using this characteristic, when combined with a putty-like biocompatible water-insoluble material, it is a dense body when adapted to a defect part of the living body, and there is no fear that the hole will be broken by external force applied at that time, In addition, a biomaterial that becomes a porous body into which cells and tissues can invade can be obtained by quickly elution of water-soluble fibers after implantation.
Furthermore, by adding appropriate ceramics to the water-insoluble material to be used, the ceramics are sintered after elution of the water-soluble fibers, which makes it difficult to control by conventional methods. Diameter) and porosity can be easily controlled, and a necessary porous body can be easily manufactured.

  As the water-soluble polymer fiber of the present invention, any water-soluble polymer fiber can be used regardless of biocompatibility. However, when the obtained porous body is used for a living body, considering the case where elution is insufficient, for example, carboxymethyl cellulose, carboxymethyl chitin, carboxymethyl chitosan, polyvinyl alcohol, polyethylene glycol, etc., or a mixture thereof It is preferable to use a water-soluble polymer having high biocompatibility such as.

  A water-insoluble biocompatible material is any resin including a thermoplastic resin and a thermosetting resin. The biocompatible material is heated before or after polymerization and dissolved in a nonpolar solvent (acetone, dichloromethane, etc.). Includes materials that can be kneaded with water-soluble polymers. For example, polylactic acid, a copolymer thereof, biocompatible biodegradable polyester containing the same, polymethyl methacrylate, and the like. In addition, the biocompatible ceramic particles are dispersed in the resin or the nonpolar solution. For example, an apatite / collagen complex putted with ethanol or acetone, a polylactic acid / calcium phosphate complex, a polyethylene / apatite complex, a polylactic acid / clay complex, and the like.

A porous body from which water-soluble polymer fibers are eluted from these may be used as it is, or may be used as a porous body in which walls are sintered by sintering ceramics or metal after pore formation. In this case, compared with the conventional method (a method in which a pore source is burned out by directly firing a molded body containing fibers), expansion of the pore portion before and after the pore source is blown out (pore source and ceramics, etc.) Therefore, a material closer to the theoretical strength can be obtained because the accumulation of strain and the generation of cracks in the porous body forming portion (wall portion) are not caused by the difference in thermal expansion coefficient.
Water or water-containing solvents (including aqueous solutions containing various ions) include tap water, pure water, purified water, distilled water, phosphate buffered saline, physiological saline, seawater, and other ions. Includes aqueous solutions and body fluids.

Lab plastics with fibers (fiber diameter 100 to 150 μm) made of polymethyl methacrylate (PMMA), which is a thermoplastic resin and biologically acceptable, and carboxymethyl cellulose (CMC), which is a water-soluble polymer, in a volume ratio as shown in Table 1. After kneading at 180 ° C. for 30 minutes in a mill (manufactured by Toyo Seiki Co., Ltd.), it was molded into a 3 mm thick and 5 cm square plate by heating and compression at 165 ° C. and 30 MPa. These were cut into 5 × 10 mm, immersed in pure water for 72 hours, and then dried overnight at 102 ° C. to prepare five types of samples. Food coloring was dropped on the compression surface and the cross section (FIGS. 1 to 26), and the state of penetration into the pores was confirmed by color (photographed with a camera).

For sample 1, the food colorant solution did not penetrate through the pores from the upper surface to the lower surface even after 60 minutes, but it penetrated partway, so it was judged as incomplete communication. Sample 2 was judged to be in communication because the dye solution permeated from the upper surface to the lower surface even when the dye solution was dropped from either side after standing for 60 minutes. Hereinafter, although the standing time was different, it was determined based on the same standard. From these, it can be concluded that the greater the amount of water-soluble fiber added, the higher the connectivity (faster permeation time). It can be concluded that there is sufficient communication.

After standing in pure water, it was confirmed that the water-soluble fiber had been eluted to the inside visually, and the weight m of the sample was measured. Further, the apparent volume Va was obtained from the outer shape of the sample, and the apparent density Da was calculated. From this density and the measured density 1.16 of the PMMA dense body used, the porosity P was determined by the following calculation. (Calculation formula is shown below)
Da = m / Va (g / cm ³ )
P = (1.16-Da) /1.16 × 100 (%)

  Table 2 shows fibers (fiber diameter: 100 to 150 μm) made of polylactic acid-glycolic acid-ε caprolactone copolymer (PLGC) which is a viscoelastic polymer and carboxymethyl cellulose (CMC) which is a water-soluble polymer. After kneading for 30 minutes at 120 ° C. in a lab plast mill (manufactured by Toyo Seiki) at a volume ratio, it was molded into a cylinder having a thickness of 10 mm and a diameter of 12 mm by heating and compression at 120 ° C. and 30 MPa. These were immersed in pure water for 72 hours and then dried overnight at -5 ° C. to prepare three types of samples. Food colorant was dropped on the compressed surface of this, and the state of penetration into the pores was confirmed by color (photographed with a camera).

Sample 6 was judged to be incomplete communication because the food colorant solution did not penetrate through the pores from the top surface to the bottom surface even after 20 minutes, but penetrated partway through. Sample 7 was judged to be in communication because the dye solution had permeated from the upper surface to the lower surface after standing for 20 minutes. Sample 8 was also judged based on the same criteria, although the standing time was different. From these, it can be concluded that the greater the amount of water-soluble fiber added, the higher the connectivity (faster permeation time), and the added amount (porosity) is at least 25% by volume (38.6% by volume). It is concluded that

After standing in pure water, it was confirmed that the water-soluble fiber had been eluted to the inside visually, and the weight m of the sample was measured. Further, the apparent volume Va was obtained from the outer shape of the sample, and the apparent density Da was calculated. From this density and the density of the PLGC dense body used, the porosity P was determined by the following calculation. (Calculation formula is shown below)
Da = m / Va (g / cm ³ )
P = (1.2-Da) /1.2 × 100 (%)

PLGC is inherently viscoelastic, but when it is made of a porous material, it deforms to about half the volume when held down with a finger (Fig. 36), but immediately returns to its original size when released (see Fig. 37).

Short fibers of HAp / Col complex having a bone-like nanostructure consisting of hydroxyapatite and collagen self-assembled fibers described in Japanese Patent No. 3379088 were synthesized and lyophilized. Thereafter, the HAp / Col composite and CMC fiber (volume ratio: composite: fiber 6: 4) were mixed in ethanol, and then subjected to compression deethanol molding. The obtained molded product was simultaneously cross-linked to de-CMC fiber and collagen in a 0.5% glutaraldehyde solution. The photograph of the obtained porous body is shown in FIG.

  It can be applied to all materials that require high connectivity. For example, a filter substrate, a medical cell / tissue scaffold material, a catalyst, an adsorbing material, a sound absorbing material, a heat insulating material and the like.

A photograph showing the state of the food dye solution penetration time 0 minutes from the cross section of Sample 1 Photograph showing food dye solution penetration time 1 minute from the cross section of sample 1 A photograph showing the state of the food dye solution penetration time of 60 minutes from the cross section of Sample 1 A photograph showing the state of the food dye solution penetration time from the compressed surface of sample 1 at 0 minutes Photo showing the state of penetration of the dye solution for food from the compressed surface of sample 1 in 1 minute A photograph showing the state of the dye solution for food penetration from the compressed surface of sample 1 at 60 minutes Photograph showing the state of the food dye solution penetration time 0 minutes from the cross section of sample 2 Photograph showing food dye solution penetration time 1 minute from cross section of sample 2 Photograph showing the state of the food dye solution penetration time 60 minutes from the cross section of Sample 2 A photograph showing the state of the food dye solution penetration time from the compressed surface of sample 2 at 0 minutes Photo showing the state of penetration of the dye solution for food from the compressed surface of sample 2 in 1 minute Photograph showing the state of the dye solution for food penetration from the compressed surface of sample 2 at 60 minutes Photograph showing the state of the food dye solution penetration time 0 minutes from the cross section of Sample 3 Photograph showing food dye solution penetration time 1 minute from the cross section of sample 3 Photograph showing the state of the food dye solution penetration time 30 minutes from the cross section of Sample 3 A photograph showing the state of the food dye solution penetration time from the compressed surface of sample 3 at 0 minutes A photograph showing the state of the food dye solution penetration time from the compressed surface of sample 3 in 1 minute Photograph showing state of food dye solution penetration time from sample 3 compression surface at 30 minutes A photograph showing the state of the food dye solution penetration time 0 minutes from the cross section of Sample 4 A photograph showing the state of the food dye solution penetration time of 0.5 minutes from the cross section of Sample 4 Photograph showing state of food dye solution penetration time 0 minutes from compressed surface of sample 4 A photograph showing the state of the food dye solution penetration time from the compressed surface of sample 4 at 0.5 minutes Photograph showing the state of the food dye solution penetration time 0 minutes from the cross section of Sample 5 A photograph showing the state of the food dye solution penetration time of 0.5 minutes from the cross section of Sample 5 A photograph showing the state of the food dye solution penetration time from the compressed surface of sample 5 at 0 minutes Photo showing the state of the food dye solution penetration time from the compressed surface of sample 5 at 0.5 minutes Photograph showing the state of sample 6 with a dye solution for food penetration of 0 minutes Photograph showing the state of sample 6 in the food dye solution penetration time of 1 minute Photograph showing the state of penetration of the dye solution for food of sample 6 at 20 minutes Photograph showing the state of sample 7 with a dye solution for food penetration of 0 minutes Photograph showing the condition of sample 7 with a dye solution for food penetration of 1 minute Photograph showing the condition of Sample 7 with a food dye solution penetration time of 20 minutes Photograph showing the condition of sample 8 with a dye solution for food penetration of 0 minutes Photograph showing the condition of sample 8 for food dye solution penetration time of 1 minute Photograph showing the condition of sample 8 with a dye solution for food penetration of 3 minutes Photo of crushing scaffold material of Example 2 with fingers Photo showing the state restored by oneself with the finger removed from the state of Fig. 36 Photograph showing scaffold material of Example 3

Claims (5)

A method for producing a porous body having a porosity of 28% or more and having pores communicating with an upper surface and a lower surface ,
A step of heat-kneading the thermoplastic resin and water-soluble polymer fiber and then molding by heat compression to produce a composite in which the water-soluble polymer fiber is mixed in a water-insoluble material ;
The complex is immersed in water or a solvent containing water (including an aqueous solution containing any ion selected from the group consisting of phosphate buffered saline, physiological saline, seawater, and body fluid ), And a step of eluting only the porous polymer fiber to make it porous.   2. The method for producing a highly communicating porous body according to claim 1, wherein the water-insoluble material is a matrix made of a biocompatible material. 2. The method for producing a highly continuous porous body according to claim 1, wherein the water-insoluble material is a matrix containing ceramics. 4. The method for producing a highly interconnected porous body according to claim 3 , wherein only the water-soluble polymer fiber is eluted from a water-insoluble material comprising a matrix containing the ceramic, and then the water-insoluble material is sintered. A method for producing a highly continuous porous body, characterized in that a porous ceramic body is obtained. 5. The method for producing a highly communicating porous body according to claim 4, wherein the ceramic is a biocompatible ceramic.