JPH06228215A - Production of temperature-sensitive porous polymer - Google Patents

Abstract

PURPOSE:To produce an arbitrary-shape porous material excellent in filtration rate, adsorption rate and desorption rate by applying energy rays to a mixture of a temperature-sensitive monomer polymerizable by application of energy rays, a crosslinkable monomer and an inert compound. CONSTITUTION:A uniform polymerizable liquid is prepared from (A) a temperature-sensitive monomer polymerizable by application of energy rays, (B) a monomer and/or an oligomer crosslinkable by application of energy rays and (C) a compound compatible with the components (A) and (B), incompatible with the polymer synthesized by application of energy rays and inert to energy rays and energy rays are applied thereto. The component (C) is removed as necessary, thus producing the objective temperature-sensitive porous polymer. An N-alkyl (meth)acrylamide or an N-alkylene (meth)acrylamide is used as the component (A) and a water-soluble substance is used as the component (C). The polymerizable liquid may contain a polymerizable nonionic monomer or oligomer in addition to the component (B). Application of energy rays may be carried out in a state where the polymerizable liquid is in contact with a reinforcing material. Ultraviolet rays or electronic beams are used as the energy rays. This polymer is capsulated.

Description

Detailed Description of the Invention

[0001]

The present invention relates to the separation of proteins, colloids, bacteria, viruses, salts, etc. in various processes such as food industry, pharmaceutical industry, electronic industry, wastewater treatment, artificial organs, desalination of seawater, etc. Ultrasensitive membranes, reverse osmosis membranes, microfiltration membranes, adsorbents, packing materials for chromatography, etc. that are used for the purpose, such as temperature-sensitive pores used in drug delivery systems that are used for the purpose of sustained drug release. The present invention relates to a method for producing a high quality polymer.

[0002]

2. Description of the Related Art In recent years, due to the sophistication of processes in the above industrial fields and the like, it is becoming difficult to simply meet the needs by simple filtration separation, adsorption and the like. Against this background, the development of intelligent systems using stimuli-responsive materials that change their functions in response to external signals and stimuli has attracted attention. As one of the stimuli-responsive materials, a hydrogel polymer that swells and shrinks upon temperature change has been discovered, and its application to drug delivery systems, filtration membranes, etc. has been actively studied.

For example, JP-A-64-58303, JP-A-63-278502, JP-A-63-134008, JP-A-61-263603, JP-A-60-250017, JP-A-60-250015 and JP-A-60-250015. 60-188411,
JOURNAL OF CHEMICAL ENGIN
EERING OF JAPAN, 23, 447 (19
90) describes its application to filtration membranes, adsorbents and packing materials for chromatography. Also, JOURNAL
OF CONTROLLED RELEASE, 16,
(1991) 215-227, JOURNAL OF
CONTROLLED RELEASE, 13, (19
90) 21-31, JOURNAL OF CONTR
OLLED RELEASE, 11 (1990) 255
-265

POLYMER JOURNAL, 23,
(1991) 1179-1189 describes application to a drag delivery system. In these examples, since the hydrogel polymer is molded by thermal polymerization of the mixture of the temperature-sensitive monomer and the crosslinkable monomer and / or oligomer, the structure has pores larger than the gel network. Absent.

[0005]

The above-mentioned hydrous gel polymer cannot be said to have sufficient performance for practical use. That is, when the water-containing gel polymer is used for a filtration membrane, an adsorbent, a drug delivery system, etc., it has a structure without pores, so that the filtration rate, the adsorption rate, the release rate, etc. of water and the drug in the polymer are It is very slow because it is dominated by the diffusion of.

Further, there is a problem that it takes too much time for the filtration rate, the adsorption rate, the release rate, etc. to change in response to the temperature change. The object of the present invention is that, when used in a filtration membrane, an adsorbent, a drug delivery system, etc., it has a sufficient speed for filtration, adsorption, release, etc., and the filtration rate, adsorption rate, release rate, etc. change due to temperature changes. It is an object of the present invention to provide a method for producing a temperature-sensitive porous polymer, which is characterized in that the time required for heating is short.

[0007]

The present inventors have completed the present invention as a result of intensive studies to solve the above problems. That is, the present invention is compatible with a temperature-sensitive monomer (A) that can be polymerized by irradiation with energy rays, a monomer and / or an oligomer (B) that can be crosslinked by irradiation with energy rays, and a mixture (A + B) thereof. However, the energy ray is applied to a uniform polymerizable liquid containing a compound (C) which is incompatible with the polymer produced by irradiating the mixture (A + B) with the energy ray and is inactive to the energy ray. After irradiation, if necessary, the compound (C)
And a method for producing a temperature-sensitive porous polymer and a method for producing a temperature-sensitive porous polymer capsule.

The term "thermosensitive monomer (A)" as used herein means that a polymer of the monomer exhibits changes such as dissolution / precipitation, swelling / contraction, binding / dissociation with other substances in accordance with temperature changes (hereinafter This change phenomenon is referred to as transition.) A monomer, for example, a linear polymer of the monomer is dissolved / precipitated according to temperature change, and a crosslinked polymer is swollen / contracted according to temperature change. Examples of temperature-sensitive monomers are N-substituted acrylamides and N-substituted methacrylamides such as N-alkyl (meth) acrylamides and / or N
-Alkylene (meth) acrylamides may be mentioned.

Examples of N-alkyl (meth) acrylamides and / or N-alkylene (meth) acrylamides are N-ethylacrylamide, N, N-diethylacrylamide, N-ethylmethacrylamide, N,
N-methylethylacrylamide, N-isopropylacrylamide, Nn-propylacrylamide, N-
Isopropylmethacrylamide, N-n-propylmethacrylamide, N-acryloylpyrrolidine, N-methacryloylpyrrolidine, N-acryloylpiperidine,
N-methacryloyl piperidine etc. can be mentioned. Among them, N-isopropylacrylamide is preferable because it causes a transition around room temperature when it is applied to various uses.

The energy ray-crosslinkable monomer (B) is not particularly limited, and the commonly used energy ray-crosslinkable monomer can be used in the present invention. Those which are compatible with each other are preferable, and typically, a monomer having two or more double bonds in one molecule, for example, methylenebisacrylamide, ethylenebisacrylamide, diethyleneglycoldi (meth) acrylate, neopentylglycoldi (meth). Acrylate,

1,6-hexanediol di (meth) acrylate, polyethylene glycol di (meth) acrylate, 2,2'-bis (4- (meth) acryloyloxypolyethyleneoxyphenyl) propane, 2,2'-
Bifunctional monomers such as bis (4- (meth) acryloyloxypolypropyleneoxyphenyl) propane, trimethylolpropane tri (meth) acrylate, trimethylolethanetri (meth) acrylate,

Examples include trifunctional monomers such as isocyanurate tri (meth) acrylate, tetrafunctional monomers such as pentaerythritol tetra (meth) acrylate, and hexafunctional monomers such as dipentaerythritol hexaacrylate. It is of course possible to use a mixture of these monomers.

There are no particular restrictions on the oligomer (B) that can be crosslinked by irradiation with energy rays, and any crosslinkable oligomer that is commonly used can be used in the present invention, but it is compatible with the temperature-sensitive monomer (A). Is preferred,
Usually, it is an oligomer having two or more double bonds in one molecule and having a weight average molecular weight of 500 to 50,000, and more specifically, energy rays such as epoxy resin, polyether resin, polybutadiene resin or polyurethane resin. Oligomers that can be crosslinked by irradiation,

For example, acrylic acid ester or methacrylic acid ester of epoxy resin, acrylic acid ester or methacrylic acid ester of polyether resin, acrylic acid ester or methacrylic acid ester of polybutadiene resin, polyurethane resin having an acrylic group or a methacrylic group at a molecular end. Etc. can be mentioned. Of course, these oligomers may be mixed and used, or may be mixed and used with a monomer.

In the present invention, in addition to the monomer and / or oligomer (B), energy is used in order to control the strength, elongation, hardness, swelling degree, response temperature, response speed, etc. of the temperature-sensitive porous polymer. Linear polymerizable monomer and /
Alternatively, it is also preferable to add the oligomer (D).

Monomer and / or oligomer (D)
Those which are compatible with the temperature-sensitive monomer (A) and the oligomer (B) are preferable, and are usually monofunctional monomers or oligomers such as acrylamide, methacrylamide, polyethylene glycol (meth) acrylate and methoxy polyethylene. Glycol (meth) acrylate, acrylic acid, methacrylic acid, vinylsulfonic acid, styrenesulfonic acid, 2-acrylamido-2-phenylpropanesulfonic acid, ethyl 2-acrylamido-2-methylpropanesulfonic acid (meth)
Acrylate,

N, N-dimethylaminoethyl (meth) acrylate, hydroxyethyl (meth) acrylate,
n-butyl (meth) acrylate, hexyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, phenyl (meth) acrylate, phenyl cellosolve (meth) acrylate, n-vinylpyrrolidone, isobornyl (meth) acrylate, dicyclopentenyl ( Examples thereof include (meth) acrylate and dicyclopentenyloxyethyl (meth) acrylate.

The compound (C) used in the present invention is compatible with the mixture (A + B).
Any polymer can be used in the present invention without particular limitation as long as it is incompatible with the polymer produced by irradiating B) with an energy beam and is inactive to the energy beam. More specifically, water, monohydric or polyhydric alcohols,
Alkyl esters such as methyl caprate, dialkyl ketones such as diisobutyl ketone, liquid polyethylene glycol, monoesters of polyethylene glycol,

Polyethylene glycol monoether,
Polyethylene glycol sorbitan monoester, polyethylene glycol sorbitan diester, polyethylene glycol sorbitan triester, polyester polyol, oligomers such as polyethylene glycol amine, cellulose acetate, ethyl cellulose,

Nitrocellulose, hydroxymethylcellulose, chitosan, polystyrene, polyvinyl chloride, polycarbonate, polysulfone, polyethersulfone, polyurethane, polyacrylonitrile, polyacrylic acid ester, polyacrylic acid, polymethylmethacrylate, polyacrylamide, Polyethylene glycol,
Polymers such as polyvinylpyrrolidone, polyvinyl methyl ether, polyvinyl alcohol and the like, and copolymers thereof are included.

Among them, the weight average molecular weight is 200 to 10
The oligomers of 000 are preferably used. Of course, the compound (C) may be a mixture of these or a mixture containing them. The compound (C) may be used without being removed after the polymer is molded by irradiation with energy rays, but it may be removed if necessary. Removal is washing,
Although any method such as drying or substitution can be adopted, when the compound (C) needs to be removed, it is preferable that the compound (C) is water-soluble because the compound (C) can be easily removed, from the viewpoint of productivity. .

The viscosity of the polymerizable liquid may vary depending on the intended shape of the porous body and the film forming method, but is preferably 1 to 1,000,000 cps at 25 ° C.
More preferably, it is 0 to 10,000 cps. Outside this range, the manufacturing conditions are more restricted.

Examples of energy rays used in the present invention include electron rays, γ rays, X rays, ultraviolet rays and visible rays. Of these, ultraviolet rays are most preferable because of the ease of use and handling. The intensity of ultraviolet rays to irradiate is 1 to
5000 mw / cm ² is preferable, and the irradiation time is 0.0
It is about 1 to 100 seconds. It is also preferable to accelerate the polymerization rate by performing irradiation of ultraviolet rays in an inert gas atmosphere. When using ultraviolet rays as energy rays,
It is also preferable to add an ultraviolet polymerization initiator to the polymerizable solution for the purpose of accelerating the polymerization rate.

The UV polymerization initiator used in the present invention is
There is no particular limitation, but a substance that can be dissolved in a polymerizable solution is preferable, and for example, p-tert-butyltrichloroacetophenone, 2,2′-diethoxyacetophenone, 2-hydroxy-2-methyl-1-phenylpropane-1- Acetophenones such as on;

Benzophenone, 4,4'-bisdimethylaminobenzophenone, 2-chlorothioxanthone, 2
-Methylthioxanthone, 2-ethylthioxanthone,
Ketones such as 2-isopropylthioxanthone; Benzoin ethers such as benzoin, benzoin methyl ether, benzoin isopropyl ether, benzoin isobutyl ether;

Examples thereof include benzyl ketals such as benzyl dimethyl ketal and hydroxycyclohexyl phenyl ketone. In the present invention, the temperature at which the polymer is formed by irradiation with energy rays is preferably the temperature at which the polymer of the mixture of monomers and / or oligomers (A + B) and the compound (C) are phase separated. A polymer obtained by polymerization at a reaction temperature at which phase separation does not occur has an incomplete formation of a porous structure, resulting in insufficient temperature responsiveness.

The formation of a porous structure in the molded polymer can be confirmed by determining whether or not polymer molecules or colloidal substances permeate the polymer. The size of the holes can be determined.

There is no restriction on the shape of the porous polymer produced by the production method of the present invention, and for example, lumps, plates, films, threads, nets, granules, hollow fibers,
It may be tubular, capsule-shaped or any other shape. A temperature-sensitive porous polymer having a desired shape can be obtained by irradiating with energy rays in a state of being molded into a desired shape, or by curing after being irradiated with energy rays and then shaping.

For example, in the case of producing a film-shaped porous body, a polymerizable liquid is cast on a support such as a metal plate, irradiated with energy rays, and then peeled off from the support, if necessary, to obtain a desired product. Can be obtained.

Further, a polymerizable liquid is extruded into a gas by using a double circular ring nozzle, and is cured by irradiating with an energy ray during a natural fall to obtain a hollow fiber-shaped, tubular or capsule-shaped porous polymer. Obtainable. The capsule made of the temperature-sensitive porous polymer according to the present invention can shrink and open depending on the temperature change and release the content to the outside. Needless to say, it is used for pharmaceuticals and agrochemicals, for chemical reaction, etc. It is also useful for industrial use.

The porous polymer of the present invention can be reinforced with a reinforcing material. Examples of reinforcing materials are threads,
Cloths, non-wovens, papers, nets and other porous materials can be mentioned. It is possible to integrate with the reinforcing material after molding the porous polymer, or it is also possible to irradiate with an energy ray in the state where the polymerizable liquid and the reinforcing material are in contact with each other to carry out integral molding.

[0032]

The present invention will be described in more detail with reference to the following examples, but the scope of the present invention is not limited thereto.

Example 1 (Preparation of Membrane) 80 parts of N-isopropylacrylamide as a temperature-sensitive monomer (A) and Unidic S9- as a crosslinkable monomer and / or oligomer (B).
414 (manufactured by Dainippon Ink and Chemicals, Inc., molecular weight 894)
Trifunctional urethane acrylate oligomer) of 20 parts,
100 parts of polyvinylpyrrolidone (PVP) having a molecular weight of 10,000 as compound (C) and 150 parts of N, N-dimethylacetamide (DMAC), and 7 parts of Irgacure 184 as an ultraviolet polymerization initiator were mixed to obtain a uniform mixture.

The polymerizable liquid was cast on a glass plate, irradiated with ultraviolet light having an ultraviolet light intensity at 365 nm of 100 mw / cm 2 at 365 nm for 60 seconds in a nitrogen atmosphere at room temperature, washed with water, and having a thickness of about 120 μm and a diameter of 45 mm. A film-like porous polymer was obtained. The temperature of the polymer immediately after irradiation was 37 ° C. The obtained porous polymer was transparent after irradiation with ultraviolet rays, but became translucent white after washing with water.

(Measurement) The obtained porous polymer was mounted in a full filtration type filtration tester, and the temperature of the stock solution for filtration was raised from 20 ° C. to 45 ° C. while applying a pressure of 1.0 kgf / cm 2 G. The permeation flux, which was 10 l / m2, h at 20 ° C. (hereinafter, the unit of permeation flow rate is the same unit), increased to a maximum value of 70 at about 37 ° C., and became 55 at 45 ° C.
At this time, the polymer was white at about 35 ° C. or higher. Then, when the temperature of the stock solution for filtration was lowered, the permeation flow rate showed a simple decrease and became 10 at 20 ° C.

The molecular weight of the stock solution for filtration is 150,000.
When a 0.01 wt% aqueous solution of polyethylene glycol was used, the polyethylene glycol concentration in the solution was
It was 0.01% by weight, the same as the stock solution. From this, it is understood that this membrane is a porous body having pores through which polyethylene glycol having a molecular weight of 150,000 is permeable.

Example 2 (Preparation of Membrane) A non-woven fabric (MF-180 manufactured by Nippon Vilene) was dipped in the same polymerizable liquid as used in Example 1 and an ultrasonic cleaner was used together with the container for the polymerizable liquid. After degassing for 5 minutes, the non-woven fabric is pulled up and placed on a glass plate, and a bar coater is used.
The excess liquid was dropped at (# 7). Then, at room temperature and in a nitrogen atmosphere, the UV intensity at 365 nm is 100.
Ultraviolet rays of mw / cm @ 2 were irradiated for 60 seconds and washed with water to obtain a membrane reinforced with a nonwoven fabric.

(Measurement) The pressure of the stock solution for filtration was set to 3.0 kgf /
The same filtration test as in Example 1 was carried out except that cm 2 G was used. The permeation flux which was 10 l / m @ 2, h at 20.degree. C. (hereinafter, the unit of permeation flux is the same unit) was 40 at 25.degree. C., 800 at 35.degree. C., and about 2000 at 45.degree. . Subsequently, when the temperature of the stock solution for filtration is lowered, the permeation flow rate becomes 3
2000 constant up to 5 ° C, 200, 2 at 25 ° C
It became 20 at 0 ° C.

Comparative Example 1 (Preparation of Membrane) A polymer was obtained in the same manner as in Example 2 except that PVP and DMAC were not added.

(Measurement) The same test as in Example 3 was conducted, but the permeation flux was very small and the measurement limit (about 0.1 l /
m2, h) or less.

Example 3 (Preparation of Membrane) 90 parts of N-isopropylacrylamide as a temperature-sensitive monomer (A) and Unidic V-4 as a crosslinkable monomer and / or oligomer (B).
5 parts of 200 (manufactured by Dainippon Ink and Chemicals, Inc., trifunctional urethane acrylate oligomer having an average molecular weight of about 2000) and 5 parts of trimethylolpropane diacrylate
Parts, 100 parts of polyvinylpyrrolidone (PVP) having a molecular weight of 10,000 as the compound (C) and 150 parts of N, N-dimethylacetamide (DMAC),

Irgacure 18 as an ultraviolet polymerization initiator
A uniform polymerizable liquid obtained by mixing 7 parts of 4 was sandwiched between two glass plates via a spacer made of silicon rubber, and the UV intensity at 365 nm was 100 mw / c at room temperature.
Irradiate with m2 of UV light for 60 seconds, wash with water, thickness 1m
A disk-shaped porous polymer having a diameter of m and a diameter of 25 mm was obtained.
The obtained porous polymer was transparent after irradiation with ultraviolet rays, but became translucent white after washing with water.

(Measurement) The porous polymer at 20 ° C. was
Put it in warm water at ℃, pull up from the water after a certain time,
The water adhering to the surface was wiped off, and the weight change of the porous polymer was measured over time. Based on the weight immediately before the addition, it became 93% after 1 minute, 80% after 10 minutes, 60% after 60 minutes, and 50% after 120 minutes, and whitened together with it.

Comparative Example 2 (Preparation of Membrane) A polymer was obtained in the same manner as in Example 3 except that PVP and DMAC were not added.

(Measurement) When the same test as in Example 3 was conducted, it was 98% after 1 minute, 88% after 10 minutes, 80% after 60 minutes, 75% after 120 minutes, and 70% after 300 minutes. The speed was slower than that of the porous body. Further, even at 30 ° C., whitening did not occur.

Example 6 (Preparation of Membrane) At 20 ° C., the same polymerizable liquid as used in Example 1 was extruded into a nitrogen atmosphere from an annular slit of a double circular ring nozzle having a diameter of 5 mm to form a double layer. From the center hole of the annular nozzle, a 0.01% aqueous solution of polyethylene glycol having a molecular weight of 50,000 was extruded as a core agent and allowed to fall naturally, while the strength at 360 nm was 6 in the vicinity of the droplets.
By irradiating with an ultraviolet ray of 00 mw / cm @ 2, spherical capsules having a diameter of about 3 mm and containing an aqueous polyethylene glycol solution were obtained.

(Measurement) This capsule was immersed in water at 15 ° C., but polyethylene glycol was not detected in the immersed water even after 30 minutes. Then, this capsule at 35 ℃
When it was put into warm water, it rapidly turned white and at the same time contracted to a diameter of about 2.5 mm, and after 1 minute, polyethylene glycol was detected in the warm water.

[0048]

Industrial Applicability According to the production method of the present invention, a porous polymer having a high filtration rate, an adsorption rate and a release rate and a high response rate to a change in temperature, that is, a filtration rate and an adsorption rate depending on a change in temperature are obtained. It is possible to manufacture a porous body in which the time required for changing the rate, the release rate, etc. is short. In addition, this method can easily form a porous body having an arbitrary shape.

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Claims (8)

[Claims] 1. A temperature-sensitive monomer (A) that can be polymerized by irradiation with energy rays, a monomer and / or an oligomer (B) that can be crosslinked by irradiation with energy rays, and a mixture thereof (A + B) are compatible with each other. , The mixture (A + B)
After irradiating the homogeneous polymerizable liquid containing the compound (C) which is incompatible with the polymer produced by irradiating the compound with the energy beam and is inactive to the energy beam, with the energy beam, if necessary. A method for producing a temperature-sensitive porous polymer, which comprises removing the compound (C). 2. The production method according to claim 1, wherein the temperature-sensitive monomer (A) is N-alkyl (meth) acrylamide and / or N-alkylene (meth) acrylamide. 3. The production method according to claim 2, wherein the N-alkylacrylamide is N-isopropylacrylamide. 4. The production method according to claim 1, 2 or 3, wherein the compound (C) is a water-soluble substance. 5. The polymerizable liquid contains, in addition to the temperature-sensitive monomer (A) and the monomer and / or oligomer (B) crosslinkable by irradiation with energy rays, a monomer and / or oligomer polymerizable by irradiation with energy rays. Any one of claims 1 to 4 which also contains (D).
Manufacturing method described in. 6. The temperature-sensitive porous polymer reinforced by the reinforcing material is produced by irradiating an energy ray with the polymerizable liquid in contact with the reinforcing material. 5. The manufacturing method according to any one of 5 to 5. 7. The manufacturing method according to claim 1, wherein the energy rays are ultraviolet rays or electron rays. 8. A method for producing a temperature-sensitive porous polymer capsule by the production method according to claim 1.