JP2009209188A - Method for producing porous polymer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for obtaining a porous polymer in a simpler and easier way (in a short period of time with less energy). <P>SOLUTION: The method for producing a porous polymer includes a step (1) of dissolving a polymer (P) in a solvent (Sv1) which does not dissolve a pore generating agent (PG) to obtain a polymer solution (PS), a step (2) of dispersing the pore generating agent (PG) in the polymer solution (PS) to obtain slurry (SL), and a step (3) where the slurry (SL) is put in a solvent-permeable tightly closed vessel (V) and this vessel is immersed in a solvent (Sv2) capable of dissolving the solvent (Sv1) and the pore generating agent (PG) to elute the solvent (Sv1) and the pore generating agent (PG) into the solvent (Sv2). <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a method for producing a porous polymer. More specifically, the present invention relates to a method for producing a porous polymer suitable as a biological tissue scaffold.

Teflon container containing 100-500 μm paraffin particles {“Teflon” is a registered trademark of EI DuPont de Nemours and Company. }, A pyridine solution of polylactic acid was dropped to obtain a slurry, and then pyridine was distilled off under reduced pressure to prepare a disk. The disk was immersed in hexane to elute paraffin to obtain porous polylactic acid. {Example 1 of Patent Document 1}: After adding a slurry of polylactic acid in tetrahydrofuran to a Teflon container containing sugar particles to obtain a slurry, the container is cooled and frozen and immersed in distilled water. To obtain porous polylactic acid by eluting tetrahydrofuran and sugar particles {Example 2 of Patent Document 1}; and a Teflon container containing 100-500 μm paraffin particles in a mixed solution of polylactic acid ( Dioxane / methanol or pyridine) was added dropwise to obtain a slurry, which was then cooled and frozen together with the container, and immersed in hexane to obtain a mixed solution and paraffin particles. Eluted with {Examples 3 and 4 of Patent Document 1} method for obtaining a porous polylactic acid are known.
US Pat. No. 6,673,285

However, the conventional manufacturing method has a problem that the manufacturing time and energy are consumed enormously.
That is, an object of the present invention is to provide a method for obtaining a porous polymer more easily {in a short time and with a small amount of energy).

The porous polymer production method of the present invention is characterized by the step (1) of obtaining a polymer solution (PS) by dissolving the polymer (P) in a solvent (Sv1) that does not dissolve the pore-forming agent (PG).
A step (2) of obtaining a slurry (SL) by dispersing a pore-forming agent (PG) in a polymer solution (PS);
The slurry (SL) is placed in a solvent-permeable airtight container (V) and immersed in a solvent (Sv2) that does not dissolve the polymer (P) but dissolves the solvent (Sv1) and the pore-forming agent (PG). Thus, the gist of the present invention includes a step (3) of obtaining a porous polymer by eluting the solvent (Sv1) and the pore-forming agent (PG) into the solvent (Sv2).

  The polymer (P) is preferably a biodegradable polymer, more preferably polylactic acid (PLA), polyglycolic acid (PGA), lactic acid / glycolic acid copolymer (PLGA), polycaprolactone, polyvalerolactone and polyhydroxybutyric acid. It is at least one selected from the group consisting of salts.

  The solvent (Sv1) is a group consisting of tetrahydrofuran, pyridine, dioxane, methanol, methylene chloride, chloroform, acetone, dimethyl sulfoxide, N-methylpyrrolidone, N, N, -dimethylmethanamide, ethyl acetate, methyl ethyl ketone, acetonitrile and dimethylformamide. At least one selected from the above is preferred.

  The solvent (Sv2) is preferably at least one selected from water, methanol, ethanol, diethyl ether, hexane and petroleum ether.

  The pore forming agent (PG) is an alkali metal halide salt, an alkali earth metal halide salt, an ammonium halide salt, an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal nitrate salt, or an alkaline earth metal nitrate. Salt, ammonium nitrate, alkali metal sulfate, alkaline earth metal sulfate, ammonium sulfate, alkali metal phosphate, ammonium phosphate, alkali metal carbonate, ammonium carbonate, alkali metal hydrogen carbonate, ammonium hydrogen carbonate At least one selected from the group consisting of alkali metal halides, alkali metal hypohalides, sugars and waxes is preferred.

  Part or all of the solvent-permeable sealed container (V) is formed of at least one selected from the group consisting of filter paper, nonwoven fabric, woven fabric, knitted fabric, porous sintered body, porous plastic molded body, and net. It is preferable.

  It is preferable to perform process (1)-(3) at 5-100 degreeC.

  The porous polymer produced by the above method is preferably used as a biological tissue scaffold.

Since the production method of the present invention uses the solvent-permeable container (V), there is an advantage that it is not necessary to freeze and elute unlike the conventional method, and the elution area is wide.
Therefore, the production method of the present invention can obtain a porous polymer more easily {in a short time and with less energy) than the conventional method.

  The pore-forming agent (PG) is generally called porogen, and the pore-forming agent (PG) is eluted from the mixture containing the pore-forming agent (PG) by elution, evaporation, sublimation or the like. By removing, pores are formed at locations where the pore-forming agent (PG) was present.

  Generally as a pore formation agent (PG), if it can be used as a porogen, it can be used without a restriction | limiting, However, What can be removed by elution is preferable.

  As the pore-forming agent (PG), alkali metal halide salts {sodium chloride, potassium chloride, potassium iodide, etc.}, alkaline earth metal halides {magnesium chloride, calcium chloride, etc.}, ammonium halide salts {salt chloride Ammonium and ammonium bromide, etc.}, alkali metal hydroxides {sodium hydroxide and potassium hydroxide, etc.}, alkaline earth metal hydroxides {magnesium hydroxide, calcium hydroxide, etc.}, alkali metal nitrates {lithium nitrate and sodium nitrate Etc.}, alkaline earth metal nitrates {magnesium nitrate, calcium nitrate, etc.}, ammonium nitrates, alkali metal sulfates {potassium sulfate, sodium sulfate, etc.}, alkaline earth metal sulfates {magnesium sulfate, calcium sulfate, etc.}, ammonium sulfate Salt {Ammonium sulfate And ammonium hydrogen sulfate}, alkali metal phosphates {potassium phosphate, disodium hydrogen phosphate, sodium phosphate, etc.}, ammonium phosphates {ammonium phosphate, diammonium hydrogen phosphate, etc.}, alkali metal carbonates { Potassium carbonate and sodium carbonate, etc.}, ammonium carbonate, hydrogen carbonate alkali metal salts {potassium bicarbonate, sodium hydrogen carbonate, etc.}, ammonium hydrogen carbonate salts, alkali metal halide salts {potassium chlorate, sodium chlorate, etc.}, next Alkali metal halides (potassium hypochlorite and sodium hypobromite, etc.), carbohydrates {monosaccharides (such as glucose and fructose), disaccharides (such as sugar, maltose and lactose) and polysaccharides (starch and oligo) Sugar etc.) and wax {melting point 40-80 ° C; Narrow wax, sugar cane wax, palm wax, beeswax, spermaceti, sperm whale oil, pearl whale oil, warts, wool wax, montan wax, paraffin wax, synthetic wax, etc.} .

  Of these pore-forming agents (PG), preferred are alkali metal halides, alkaline earth metal halides, alkali metal sulfates, alkali metal carbonates, alkali metal hydrogen carbonates, carbohydrates and waxes. Alkali metal halides and saccharides are preferable, and sodium chloride, sugar and starch are particularly preferable.

  The shape of the pore-forming agent (PG) is appropriately determined depending on the shape of the pores of the target porous polymer, and is spherical, spindle-shaped, cylindrical, conical, polygonal columnar, polygonal pyramidal, cubic, rectangular parallelepiped, fibrous and Includes mesh. Among these, a cube, a rectangular parallelepiped and a sphere are preferable. You may use combining the pore formation agent (PG) from which a shape differs.

The size of the pore-forming agent (PG) is appropriately determined depending on the pore size of the target porous polymer, and includes, for example, those having a volume of 0.001 to 8 cm ³ . Among these, it preferred 0.001～3.75Cm ^3, more preferably 0.001～1Cm ^3, particularly preferably 0.009~0.512cm ^3. You may use combining the pore formation agent (PG) from which a magnitude | size differs {A pore ratio can be made high by combining a large thing and a small thing. }.

As the solvent (Sv1), any solvent can be used as long as it does not dissolve the pore-forming agent (PG) but dissolves the polymer (P). Tetrahydrofuran, pyridine, 1,4-dioxane, methanol, methylene chloride , Chloroform, acetone, dimethyl sulfoxide, N-methylpyrrolidone, N, N, -dimethylmethaneamide, ethyl acetate, methyl ethyl ketone, acetonitrile, and dimethylformamide.
Of these solvents (Sv1), tetrahydrofuran, acetone and 1,4-dioxane are preferred.

  The polymer (P) is not particularly limited as long as it is a porous polymer that can be dissolved in the solvent (Sv1), but a biodegradable polymer is preferable, and polylactic acid (PLA), At least one selected from the group consisting of glycolic acid (PGA), lactic acid / glycolic acid copolymer (PLGA: monomer molar ratio 40/60 to 98/2), polycaprolactone, polyvalerolactone and polyhydroxybutyrate It is.

The weight average molecular weight of the polymer (P) is preferably 5,000 to 2,000,000, more preferably 5,000 to 500,000, particularly preferably 10,000 to 200,000.
The weight average molecular weight is measured by gel permeation chromatography using polyethylene glycol as a reference substance.

  The concentration (% by weight) of the polymer (P) is preferably 0.01 to 50, more preferably 1 to 30, particularly preferably 5 to 20, based on the weight of the solvent (Sv1). Within this range, a porous polymer can be obtained even more easily {in a short time with less energy}.

The dissolution temperature (° C.) is not limited as long as the polymer (P) can be dissolved, but it is preferably 0 to 150, more preferably 5 to 100, and more preferably 5 to 100 in order to more easily dissolve {in a short time with less energy}. Preferably it is 10-90, Most preferably, it is 20-80.
In addition, as an apparatus for making it melt | dissolve, a normal stirring and mixing apparatus etc. can be used.

  The viscosity (mPa · s) of the polymer solution (PS) is preferably 1 to 50,000, more preferably 20 to 20,000, and particularly preferably 100 to 5000. Within this range, a porous polymer can be obtained even more easily {in a short time with less energy}. The viscosity is measured according to JIS K7117-1: 1999 {25 ° C.} {for example, Brookfield type rotational viscometer HBDV-III, manufactured by Brookfield, Inc.}.

  The slurry (SL) may be dispersed by adding (1) a pore forming agent (PG) to the polymer solution (PS), or (2) adding the polymer solution (PS) to the pore forming agent (PG). May be dispersed. In the case of the latter (2), a pore-forming agent (PG) is added to the solvent-permeable airtight container (V) {if necessary, the solvent-permeable airtight container (V) may be vibrated or heated. Or a solvent (Sv2) may be added to fuse the pore-forming agents (PG) together. } A polymer solution (PS) may be added thereto.

  The volume ratio (PG / P) between the pore-forming agent (PG) and the polymer (P) is preferably 100/1 to 1/100, more preferably 50/1 to 1/1, and particularly preferably 50/1. 5/1. When this volume ratio is 5/1 or less, the pores contained in the obtained porous polymer are likely to be independent pores, whereas when larger than 5/1, they are likely to be continuous pores.

  The temperature (° C.) in the step (2) is not particularly limited, but is preferably the same temperature as the step (3). In addition, as an apparatus for disperse | distributing, a normal stirring mixing apparatus etc. can be used.

  The solvent-permeable airtight container (V) is a material that can freely permeate the solvent (Sv2) solution of the solvent (Sv1), the solvent (Sv2), and the pore forming agent (PG), and constitutes a part or all of the container. It is a container which can be sealed after putting slurry (SL).

  Examples of materials that can freely pass through the solvent (Sv1), the solvent (Sv2) and the solvent (Sv2) solution of the pore forming agent (PG) include filter paper, nonwoven fabric, woven fabric, knitted fabric, porous sintered body, porous material At least one selected from the group consisting of a plastic molding and a net is included. Of these, filter paper and nonwoven fabric are preferred from the viewpoint of processability and the like. These materials are not limited as long as they are not dissolved, swelled or corroded in the solvent (Sv1) and the solvent (Sv2) and do not affect the polymer (P) and the pore forming agent (PG) (for example, , Including paper, wood, plastic, metal, glass and ceramics). Moreover, there is no restriction | limiting in the magnitude | size and shape of a solvent-permeable airtight container (V), and it determines suitably by manufacturing amount etc.

  The solvent (Sv2) that can dissolve the solvent (Sv1) and the pore-forming agent (PG) is any solvent that does not dissolve the polymer (P) but dissolves the solvent (Sv1) and the pore-forming agent (PG). A normal solvent can be used, and includes at least one selected from water, methanol, ethanol, diethyl ether, hexane and petroleum ether. Of these solvents (Sv2), water is preferred.

  The amount of use (volume%) of the solvent (Sv2) is preferably 100 or more, more preferably 500 or more, particularly preferably 1000 or more, based on the volume of the solvent (Sv1). Within this range, the solvent (Sv1) and the pore forming agent (PG) can be sufficiently removed.

  The solvent (Sv2) may be used at a time, but it is preferable to use it in a plurality of times {for example, 2 to 10 times) in order to dissolve it {in a short time with less energy}, More preferably, it is used while continuously replacing a part.

  When used while continuously replacing a part, for example, using an apparatus as shown in FIG. 1 (pipe so that liquid can be discharged from the lower part of the cylindrical container), the solvent (Sv2) is supplied from the solvent inlet (1). And a solution of the solvent (Sv2) in which the solvent (Sv1) and the pore forming agent (PG) are dissolved may be discharged from the discharge port (2).

  The immersion temperature (° C.) is not limited as long as the solvent (Sv1) and the pore-forming agent (PG) can be dissolved (transferred) into the solvent (Sv2), but more easily {dissolve in a short time with less energy}. Is preferably from 0 to 150, more preferably from 5 to 100, particularly preferably from 10 to 90, and most preferably from 20 to 80. The immersion temperature may be changed {for example, a method of starting immersion at a low temperature and gradually increasing the temperature. }. In addition, it is not necessary to freeze slurry (SL) before immersion {If it freezes, the speed | rate of elution of a solvent (Sv1) and a pore formation agent (PG) will fall remarkably. }

  Solvent permeable airtight container (V) {including slurry (SL). } May be swung while the solvent (Sv2) is immersed in the solvent (Sv2), and the solvent (Sv2) may be swung or stirred.

  After eluting the solvent (Sv1) and the pore-forming agent (PG) from the slurry (SL) into the solvent (Sv2), the porous polymer is pulled up from the solvent (Sv2) together with the solvent-permeable airtight container (V). It is preferable to include a liquid draining step (4) for draining liquid. The solvent-permeable airtight container (V) may be suspended and drained by gravity alone, or may be drained using a centrifuge, or a combination of these may be drained.

It is preferable to include a drying step (5) after the liquid draining step (4). The porous polymer may be dried after being taken out from the solvent-permeable sealed container (V), or may be dried together with the solvent-permeable sealed container (V) and then taken out from the solvent-permeable sealed container (V). Good.
Drying may be performed by heating, cooling (freezing), non-heating, ventilation, non-ventilation, or decompression. However, it is not necessary to reduce the pressure.
Of these, drying combined with heating-ventilation, heating-depressurization, or cooling (freezing) -depressurization is preferable, more preferably drying combining heating-depressurization or cooling (freezing) -depressurization, particularly preferably cooling ( Freezing)-reduced pressure {freeze drying}.

  In many cases, the porous polymer is in close contact with the solvent-permeable airtight container (V) both before and after drying. For this reason, the porous polymer may be taken out by cutting the vicinity of the interface between the solvent-permeable airtight container (V) and the porous polymer.

  The dried porous polymer can be appropriately cut to adjust the shape or sterilized depending on the application.

  The porous polymer produced by the production method of the present invention is suitable as a biological tissue scaffold. That is, as a biological tissue scaffold for culturing and proliferating cells collected from a patient, seeding it on a biological tissue scaffold, culturing it, preparing a target cell hybrid structure, and then transplanting it into the patient's body ,Is suitable.

<Example 1>
In a 100 ml glass flask, 4 g of polymer (p1) {polylactic acid, BM Corporation, weight average molecular weight 200,000} is dissolved in 36 g of solvent (sv11) {1,4-dioxane} at about 80 ° C. A weight percent polymer solution (ps1) was obtained. Next, 40 g of this polymer solution (ps1) was transferred to a 300 ml plastic beaker, and 100 g of pore forming agent (pg1) {sugar, cubic ultrafine sugar, weight average particle diameter 600 μm, Sakai Shoten Co., Ltd.} was added, and mixed uniformly. A slurry (sl1) was obtained.

  The slurry (sl1) was poured into a solvent-permeable airtight container (v1) {Cylinder filter paper for Soxhlet extraction, manufactured by Whatman Co., Ltd.}, and after vibration was applied uniformly (no gap), the solvent-permeable airtight container The upper opening of (v1) was folded and sealed.

  The sealed solvent-permeable airtight container (v1) was immersed in 2000 g of a 30 ° C. solvent (sv21) {distilled water, produced with an automatic distilled water production apparatus (Aquarius GS-200: Advantech Toyo Co., Ltd.)} Left for hours.

  After 24 hours, the solvent-permeable airtight container (v1) {including the porous polymer} was lifted from the solvent (sv21), and then put into 1000 g of a new solvent (sv21) at 30 ° C for 10 minutes. went. Further, after performing ultrasonic cleaning twice using a new solvent (sv21), the drained solvent-permeable airtight container (v1) {including porous polymer} is opened, and the wet porous polymer is taken out. Cut into 10 mm × 10 mm × 10 mm cubes. The cube was dried (60 ° C., 12 hours) in a blown constant temperature dryer (DRX620DA, Advantech Toyo Co., Ltd.) to obtain a porous polymer (1). The porosity (porosity) of the porous polymer (1) was 96% by volume.

  In addition, the porosity measured the weight (w) of the porous polymer (1), and computed it from following Formula (henceforth calculated | required similarly).

(Porosity) = (1000 × (w) / (ρ1)) × 100/1000

  However, (ρ1) is the density of the polymer (p1) {polylactic acid}, and a value of 1.25 was used.

<Example 2>
“Solvent permeable airtight container (v1)” was changed to “solvent permeable airtight container (v2)” and sealed as follows, and “pore forming agent (pg1)” was changed to “pore forming agent”. (Pg2) A porous polymer (2) was obtained in the same manner as in Example 1 except that it was changed to {sugar, cubic ultrafine sugar, weight average particle diameter 1.5 mm, Sakai Shoten Co., Ltd.}. The porosity (porosity) of the porous polymer (2) was 96% by volume.

  “Solvent-permeable airtight container (v2)” is filter paper {No. 2 filter paper, Advantech Toyo Co., Ltd.} cylinder 8 mm in diameter and 1.2 cm in height (3) {both ends of the rectangular parallelepiped filter paper were stopped with a stapler. }, A circular filter paper (4) having a diameter of 9 cm is disposed in both openings, and a circular wire mesh (5) having a mesh opening of 2 mm is disposed on the outer side thereof. 6) (7) {2 cm x 1.2 cm x 9 cm made of wood} are arranged in parallel to each other, and two bars {bar (6) and bar {7} is a container that is hermetically sealed by fastening it with a rubber band (8) {FIG. 2}.

  The slurry has a cylindrical tube (3) {one opening provided with a circular filter paper (4), a circular wire mesh (5), and a rod (7). }, The other opening is sealed with a circular filter paper (4) and a circular wire mesh (5), and the bar (6) and bar (7) are sealed with a rubber band (8). did.

<Example 3>
The “solvent permeable airtight container (v1)” was changed to “solvent permeable airtight container (v2)” and sealed as described above, and “pore forming agent (pg1)” was changed to “pore forming agent (pg1)”. pg3) {sugar, cubic ultrafine sugar, weight average particle size 300 μm, Sakai Shoten Co., Ltd.} and “polymer (p1)” is changed to polymer (p2) {RESOMER LT706, Nippon Boehringer Ingelheim Co., Ltd. Lactic acid / trimethylene carbonate copolymer (68-72 mol / 32-28 mol), “RESOMER”, is a registered trademark of Behringer Ingelheim Comandate Geselsyaft. }] Was obtained in the same manner as in Example 1 except that the porous polymer (3) was obtained. The porosity (porosity) of the porous polymer (3) was 96% by volume. However, the value (1.25) of the density (ρ2) of the polymer (p2) was used.

<Example 4>
The “solvent permeable airtight container (v1)” was changed to “solvent permeable airtight container (v2)” and sealed as described above, and “polymer (p1)” was changed to polymer (p3) {RESOMER LC703S. In the same manner as in Example 1, except that the lactic acid / ε-caprolactone copolymer (67-73 mol / 33-27 mol) manufactured by Nippon Boehringer Ingelheim Co., Ltd.} 4) was obtained. The porosity (porosity) of the porous polymer (4) was 96% by volume. However, a value of 1.25 was used for the density (ρ3) of the polymer (p3).

<Example 5>
4 g of the polymer (p1) was dissolved in 36 g of the solvent (sv12) {dioxane / pyridine (50% by volume / 50% by volume)} at about 60 ° C. to obtain a polymer solution (ps2).

  In a solvent-permeable airtight container (v2), 100 g of a pore forming agent (pg4) {paraffin particles having a melting point of 53 to 57 ° C. obtained in the same manner as in Example 1 of Patent Document 1 and a weight average particle diameter of 600 μm} After the slurry (sl1) was prepared by adding 40 g of the polymer solution (ps2), the solvent-permeable sealed container (v2) was sealed as described above.

  After putting 2 liters of solvent (sv22) {hexane} into a 2 liter glass beaker, the solvent-permeable airtight container (v2) {including slurry (sl2)} is immersed and the total amount of solvent (sv22) every 4 hours. Was carried out in a constant temperature room at 40 ° C. }.

  After 24 hours, the solvent-permeable airtight container (v1) {including the porous polymer} was pulled up from the solvent (sv22), and then placed in 1000 liters of a new solvent (sv22) at 30 ° C for 10 minutes by ultrasonic cleaning. Went. Furthermore, after performing ultrasonic cleaning twice using a new solvent (sv22), the solvent-permeable solvent-permeable sealed container (v1) {including porous polymer} is opened and the wet porous polymer is removed. The sample was taken out and cut into 10 mm × 10 mm × 10 mm cubes. The cube was dried (60 ° C., 12 hours) in a blowing constant temperature dryer (DRX620DA, Advantech Toyo Co., Ltd.) to obtain a porous polymer (5). The porosity (porosity) of the porous polymer (5) was 96% by volume.

<Example 6>
4 g of the polymer (p1) was dissolved in 36 g of the solvent (sv13) {pyridine} at about 60 ° C. to obtain a polymer solution (ps3).

  A solvent-permeable airtight container (v2) is charged with 100 g of a pore-forming agent (pg4), and 40 g of a polymer solution (ps2) is added to prepare a slurry (sl1). And sealed.

  After putting 2 liters of solvent (sv22) {hexane} into a 2 liter glass beaker, the solvent-permeable airtight container (v2) {including slurry (sl2)} is immersed and the total amount of solvent (sv22) every 4 hours. Was carried out in a constant temperature room at 40 ° C. }.

  After 24 hours, the solvent-permeable airtight container (v1) {including the porous polymer} was pulled up from the solvent (sv22), and then placed in 1000 liters of a new solvent (sv22) at 30 ° C for 10 minutes by ultrasonic cleaning. Went. Furthermore, after performing ultrasonic cleaning twice using a new solvent (sv22), the solvent-permeable solvent-permeable sealed container (v1) {including porous polymer} is opened and the wet porous polymer is removed. The sample was taken out and cut into 10 mm × 10 mm × 10 mm cubes. The cube was dried (60 ° C., 12 hours) in a blowing constant temperature dryer (DRX620DA, Advantech Toyo Co., Ltd.) to obtain a porous polymer (6). The porosity (porosity) of the porous polymer (6) was 96% by volume.

<Example 7>
The “solvent permeable airtight container (v1)” was changed to “solvent permeable airtight container (v2)” and sealed as described above, and the “sealed solvent permeable airtight container (v1) was 30 ° C. A porous polymer (7) was obtained in the same manner as in Example 1 except that the solvent (sv21) {distilled water} was immersed in 2000 g and allowed to stand for 24 hours. The porosity (porosity) of the porous polymer (7) was 96% by volume.

  Pipette washer {piped so that liquid can be discharged from the lower part of a cylindrical container, manufactured by Samplatec Co., Ltd .; Fig. 1} is filled with solvent (sv23) {tap water} and then sealed with a solvent-permeable sealed container (v1 ) Immerse {including slurry}, let the solvent (sv23) flow in from the solvent inlet (1) of the pipette washer at a flow rate of 100 ml / min, and remove the solvent (sv11) and finer from the outlet (2). The solution of the solvent (sv23) in which the pore forming agent (pg1) was dissolved was discharged {the temperature of the discharged solution was 28 ° C. }.

<Comparative Example 1>-Example 2- of Patent Document 1
Polytetrafluoroethylene container {having a recess with a diameter of 8 cm and a depth of 1.2 cm. } Was added 100 g of a pore forming agent (pg1), 40 g of a polymer solution (ps1) obtained in the same manner as in Example 1, and then placed in a −20 ° C. freezer.

  After putting 2 liters of solvent (sv21) {distilled water} into a 2 liter glass beaker, a polytetrafluoroethylene container {including slurry} was immersed and the total amount of solvent (sv21) was changed every 12 hours { Performed in a 10 ° C. refrigerator. }.

  24 hours later, after the polyethylene fluoroethylene container {including the porous polymer} was pulled up from the solvent (sv21), the porous polymer was taken out from the polyethylene fluoroethylene container, and the solvent (sv21) was wiped off with filter paper. It was. Subsequently, the porous polymer was dried under reduced pressure {−10 ° C., 67 Pa} for 168 hours to obtain a comparative porous polymer (H1). The porosity (porosity) of the porous polymer (H1) was 96% by volume.

<Comparative Example 2>-Example 4 of Patent Document 1
Polytetrafluoroethylene container {having a recess with a diameter of 8 cm and a depth of 1.2 cm. } Was added 100 g of a pore-forming agent (pg4), 40 g of the polymer solution (ps1) obtained in the same manner as in Example 1, and then placed in a freezer at −70 ° C.

  After putting 2 liters of solvent (sv22) {hexane} into a 2 liter glass beaker, a polytetrafluoroethylene container {including slurry} was immersed, and the entire amount of solvent (sv22) was changed every 12 hours {- Performed in an 18 ° C. freezer. }.

  24 hours later, after pulling up the polytetrafluoroethylene container {including the porous polymer} from the solvent (sv22), take out the porous polymer from the polyethylenefluoroethylene container, and filter the solvent (sv22) and the like. Wiped off. Subsequently, the porous polymer was dried under reduced pressure {−10 ° C., 27 Pa} for 168 hours to obtain a comparative porous polymer (H2). The porosity (porosity) of the porous polymer (H2) was 96% by volume.

<Comparative Example 3> -Example 1 of Patent Document 1
4 g of the polymer (p1) was dissolved in 36 g of the solvent (sv13) {pyridine} at about 60 ° C. to obtain a polymer solution (ps3).

  Polytetrafluoroethylene container {having a recess with a diameter of 8 cm and a depth of 1.2 cm. } Was added 100 g of a pore-forming agent (pg4) and 40 g of a polymer solution (ps3), and then pyridine was distilled off under reduced pressure {−10 ° C., 27 Pa} over 7 days. Subsequently, the content {a disc-shaped composite composed of the polymer (p1) and the pore forming agent (pg3)} was taken out from the polytetrafluoroethylene container.

  After putting 2 liters of solvent (sv22) {hexane} into a 2 liter glass beaker, the contents {disk-like composite} were immersed and the entire amount of solvent (sv22) was replaced every 12 hours {−18 ° C. freezer Went in. }.

  After 24 hours, after the porous polymer was pulled up from the solvent (sv22), the solvent (sv22) and the like were wiped off with a filter paper. Subsequently, the porous polymer was dried under reduced pressure {−10 ° C., 67 Pa} for 168 hours to obtain a comparative porous polymer (H3). The porosity (porosity) of the porous polymer (H2) was 96% by volume.

  In Examples 1 to 7 and Comparative Examples 1 to 3, an approximation was calculated from the time and electric energy required for the step (1), the step (2) and the step (3) and the rated power of the apparatus used. } Is shown in Table 1.

  As in Examples 1 to 7, the production method of the present invention was able to efficiently obtain a porous polymer in a shorter time and with less energy compared to the method of the comparative example. Moreover, the porosity of the obtained porous polymer was equal to or higher than that obtained in the comparative example.

It is the perspective view which showed typically the pipette washing device used in the Example. It is the perspective view which decomposed | disassembled and showed typically about the solvent-permeable airtight container used in the Example {Three pieces are omitted among four-wheel rubber. }.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Solvent input port 2 Outlet port 3 Cylindrical tube 4 Circular filter paper 5 Circular wire mesh 6 Bar material 7 Bar material 8 Rubber band

Claims (9)

A step (1) of obtaining a polymer solution (PS) by dissolving the polymer (P) in a solvent (Sv1) that does not dissolve the pore-forming agent (PG);
A step (2) of obtaining a slurry (SL) by dispersing a pore-forming agent (PG) in a polymer solution (PS);
The slurry (SL) is placed in a solvent-permeable airtight container (V) and immersed in a solvent (Sv2) that does not dissolve the polymer (P) but dissolves the solvent (Sv1) and the pore-forming agent (PG). And a step (3) of obtaining a porous polymer by eluting the solvent (Sv1) and the pore-forming agent (PG) into the solvent (Sv2).   The method according to claim 1, wherein the polymer (P) is a biodegradable polymer.   The polymer (P) is at least one selected from the group consisting of polylactic acid (PLA), polyglycolic acid (PGA), lactic acid / glycolic acid copolymer (PLGA), polycaprolactone, polyvalerolactone, and polyhydroxybutyrate The method according to claim 1 or 2.   The solvent (Sv1) is a group consisting of tetrahydrofuran, pyridine, dioxane, methanol, methylene chloride, chloroform, acetone, dimethyl sulfoxide, N-methylpyrrolidone, N, N, -dimethylmethanamide, ethyl acetate, methyl ethyl ketone, acetonitrile and dimethylformamide. The method according to any one of claims 1 to 3, which is at least one selected from the group consisting of more than one.   The method according to any one of claims 1 to 4, wherein the solvent (Sv2) is at least one selected from water, methanol, ethanol, diethyl ether, hexane and petroleum ether.   The pore forming agent (PG) is an alkali metal halide salt, an alkaline earth metal halide salt, an ammonium halide salt, an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal nitrate salt, an alkaline earth metal nitrate. Salt, ammonium nitrate, alkali metal sulfate, alkaline earth metal sulfate, ammonium sulfate, alkali metal phosphate, ammonium phosphate, alkali metal carbonate, ammonium carbonate, alkali metal hydrogen carbonate, ammonium hydrogen carbonate The method according to any one of claims 1 to 5, which is at least one selected from the group consisting of alkali metal halides, alkali metal hypohalides, sugars and waxes.   Part or all of the solvent-permeable sealed container (V) is formed of at least one selected from the group consisting of filter paper, nonwoven fabric, woven fabric, knitted fabric, porous sintered body, porous plastic molded body, and net. The method according to claim 1.   The method in any one of Claims 1-7 which perform process (1)-(3) at 5-100 degreeC.   The biological tissue scaffold using the porous polymer manufactured by the method in any one of Claims 1-8.

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