JP2005132843A - Method for using stimulus sensitive material - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for using a stimulus sensitive material independently responding to each of a plurality of stimuli. <P>SOLUTION: This invention relates to the method for using the stimulus sensitive material comprising use of a block or graft copolymer expressed by the formula A<SB>m</SB>B<SB>n</SB>comprising a polymer chain A and a polymer chain B having mutually different solubility parameters, (in the formula, (m) and (n) are each an integer of 1-5), as the main constituting component, and changing affinity to a biological component and/or a medicament by independently changing either one of its space volume such as length, area or volume responding to at least two stimulus conditions. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a stimulus-responsive material accompanied by a change in the amount of space by giving a stimulus in the presence of water. More specifically, the present invention relates to a method of using a material capable of reversibly repeating swelling and shrinkage due to temperature change and / or pH change.

  Many polymers and materials that exhibit stimulus responsiveness have been known so far, and temperature, light, pH, ion concentration, potential, solvent affinity, and the like are used as the stimulus.

  For example, acrylamide polymers such as poly-N-isopropylacrylamide and polyvinyl methyl ether are known as examples showing temperature responsiveness, and polyacrylic acid / PVA blends are known as examples showing pH responsiveness, Attempts have been made to use artificial muscles and other actuators, energy conversion materials, controlled release of drugs, and cell culture.

  Such stimulus responsiveness is basically caused by repeated absorption of liquid (water) into the material matrix and elimination of liquid (water) from the matrix. In conventional materials, there is no single response to a plurality of stimuli, and only a single function and a single function are known. For this reason, the application has to be extremely limited.

  In view of such a situation, the present invention is to provide a method of using a stimulus-responsive material that exhibits independent responses to a plurality of stimuli.

  In order to respond to multiple stimuli, it is thought that the objective can be basically achieved by mixing each stimulus-responsive material, but in reality, many polymers are incompatible with each other and do not mix In general, finding a compatible system requires a great deal of effort, and even if a compatible system is found, the application development is extremely limited. The inventors of the present invention have found that these problems can be solved by using a polymer that responds to each stimulus to form a block or graft copolymer. That is, the present invention is achieved by the following.

(1) Utilizing a material whose main constituent is a block or graft copolymer represented by the general formula AmBn (m, n is an integer of 1 to 5) composed of polymer chains A and B having different solubility parameters And a stimulus response characterized by changing the affinity with a biological component and / or a drug by independently changing the amount of space in length, area, or volume independently of at least two stimulus conditions. How to use sex materials.
(2) The use method according to (1), wherein at least a temperature change and / or a pH change is included in the two or more stimuli.
(3) The utilization method according to the above (1) or (2), wherein the stimulation response utilization method separates and purifies a biological component and / or a drug.
(4) The utilization method according to (1) or (2) above, wherein the stimulation response utilization method cultures cells.

  The method of using the stimuli-responsive material of the present invention responds to mild stimuli because it is considered to be mainly used for artificial muscles, controlled release of drugs, separation and purification of biological components such as proteins, and cell culture. Is desired.

  In the block or graft copolymer represented by the general formula AmBn constituting the stimulus responsive material used in the present invention, when both of the polymer chains A and B have temperature responsiveness, one is temperature responsive and the other is When it has pH responsiveness, it may have pH responsiveness together. It is desired that the temperature responsiveness is expressed in the range of 0 ° C to 70 ° C. If it is 0 ° C. or lower, problems such as freezing occur because the conditions for using the material of the present invention are aqueous, and if it is 70 ° C. or higher, problems such as degeneration occur for biological components such as proteins. The pH responsiveness is desirably expressed in the range of pH 3 to pH 11. A pH of 2 or lower, or a pH of 12 or higher, is undesirable because problems such as degeneration occur for biological components such as proteins. When the polymer chains of A and B are temperature responsive, the difference in transition temperature is preferably 5 ° C. or more. Below this, the phase change associated with the secondary stimulus becomes unclear, which is undesirable in terms of function expression. When the polymer chains A and B are responsive to pH, it is desirable that the amount of change in pH that serves as a primary and secondary stimulus is 2 or more. Below this, changes associated with secondary stimulation become unclear, which is undesirable in terms of function expression.

  N-alkyl-substituted acrylamides such as N-isopropylacrylamide, vinyl ethers such as (meth) acryloyloxyethyl pyrrolidone, vinyl methyl ether, etc. as monomers for deriving temperature-responsive polymer chains, methyl cellulose as the polymer chain, 12 % Acetylated polyvinyl alcohol, polyethylene oxide and the like can be mentioned, but they may be copolymerized with other vinyl monomers as long as the temperature responsiveness is not affected. Specific examples include (meth) acrylic esters such as methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, vinyl esters such as vinyl acetate and vinyl propionate, styrene, vinyl chloride, Vinyl compounds such as N-vinylpyrrolidone and (meth) acrylamides can be used.

  Monomers that induce a pH-responsive polymer chain include monomers having a dissociation group such as (meth) acrylic acid, styrenesulfonic acid, 2-acrylamido-2-methylpropanesulfonic acid, etc., but the pH-responsiveness is affected. Other vinyl monomers in a range such as (meth) acrylates such as methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, vinyl esters such as vinyl acetate and vinyl propionate, styrene, It can be copolymerized with vinyl compounds such as vinyl chloride and N-vinylpyrrolidone, and (meth) acrylamides.

  The molecular weight of the polymer chain represented by A or B is preferably about 1000 to 50000. If it is 1000 or less, the stimulus response capability is not sufficient, and the change in the space amount is insufficient. On the other hand, when it becomes 50000 or more, it becomes difficult in terms of synthesis.

  The method for synthesizing the block or graft copolymer of the present invention can be prepared by a known method. When synthesizing a block copolymer, a living polymerization method, a method of synthesizing a polymer chain having an amino group, a hydroxyl group, a carboxyl group or the like introduced at both ends or one end and coupling them, an iniferter is used. The radical polymerization method that has been used. The graft copolymer can be synthesized by synthesizing a macromonomer corresponding to the A chain or B chain and then performing radical or anionic polymerization. In addition, since the polymer chain which expresses pH responsiveness has active hydrogen, it cannot use for anion polymerization or a coupling reaction as it is. At that time, the purpose is achieved by protecting the carboxyl group by esterification and removing the protecting group by hydrolysis after copolymerization.

  Although the block or graft copolymer represented by the general formula AmBn used in the present invention has stimuli responsiveness, it may be dissolved in water depending on the conditions. It is desirable. This method can be achieved by cross-linking by γ-ray irradiation or chemical cross-linking using a polyfunctional monomer. It can also be achieved by confining IPN in a water-insoluble gel such as polyvinyl alcohol or poly 2-hydroxyethyl methacrylate.

  The block or graft copolymer in the present invention is a binary system of A and B, but it is a multi-component copolymer into which a polymer chain C or D is introduced, and three or more kinds of stimuli are used. It does not exclude that response is possible.

  In the stimuli-responsive material mainly comprising a block or graft copolymer represented by the general formula AmBn of the present invention, the A chain and the B chain have different solubility parameters, so that proteins, polysaccharides, Affinities (interactions) with biological components such as lipids and cellular components and drugs are different. Therefore, selectivity can be expressed for two or more kinds of substances, and the adsorption and release of these substrates can be controlled independently according to each stimulus. Therefore, it is suitable as a material for separation and purification or a material for control release. In addition, since the volume changes with respect to the primary stimulus and the secondary stimulus each time, the actuator can obtain an unprecedented high-order mobility. In addition, the stimulus-responsive material can be used as a chemical valve or the like by immobilizing on the surface of the porous membrane or the surface of the porous beads.

  EXAMPLES The present invention will be specifically described below using examples, but the scope of the present invention is not limited to only the examples.

(Example 1)
A glass polymerization tube was charged with 0.1 mol of N-isopropylacrylamide, 0.5 mmol of azobisisobutyronitrile, 0.07 mol of aminoethanethiol, and 30 ml of DMF as a solvent, sealed in a vacuum and polymerized at 60 ° C. As a result of identification after reprecipitation purification, it was found to be a polymer (PIPAm) having a number average molecular weight of 2500 in which one amino group was introduced per molecule.

  0.1 mol of methacryloyloxyethyl pyrrolidone and 3 mmol of p, p'-diisocyanate diphenyl disulfide were placed in a Pyrex glass polymerization container, degassed, and then irradiated with UV light from a mercury lamp and subjected to photopolymerization at 30 ° C. for 12 hours. As a result of identification after reprecipitation purification, a polymer (PMEP) having a number average molecular weight of 7,800 and an isocyanate number of 1.98 in one molecule was obtained.

  The one-terminal aminated PIPAm and both-end diisocyanated MEP are dissolved in DMF so that the ratio of terminal functional groups before the reaction (isocyanate: amino group) is 1: 1 and coupled at 0 ° C. for 48 hours. Reaction was performed and the block copolymer was obtained.

  When the DSC of this block copolymer was measured under water, the transition temperatures were observed at 34 ° C. and 50 ° C. The copolymer was dissolved in DMF, butanediol and pyridine as a catalyst were added and cast on a glass plate, and then heated to 80 ° C. to introduce chemical crosslinking. After vacuum drying and distilling off DMF and the like, it was immersed in cold water to obtain a hydrous gel. It was found that when the temperature of the gel was 40 ° C., it contracted and then when it was 60 ° C., it further contracted and responded independently to each stimulus.

(Example 2)
Single-terminal aminated PIPAm was prepared in the same manner as in Example 1. In addition, polytrimethylsilyl methacrylate (PTMSM) was prepared by photopolymerization in the same manner as in Example 1 as a prepolymer of both terminal diisocyanates. Coupling reaction was carried out with both to perform block copolymerization, and then 1N hydrochloric acid was added to the reaction system to hydrolyze the silyl ester to obtain a copolymer of isopropylamide and methacrylic acid. After reprecipitation purification, it was dissolved in DMF, and toluene diisocyanate was added thereto to introduce chemical crosslinks to form a gel, followed by solvent substitution to obtain a hydrous gel.

  The gel swelled below 30-35 ° C. and shrunk above that temperature. Next, when the gel was maintained in warm water at 40 ° C. and an aqueous sodium hydroxide solution was added to adjust the pH to 10, the gel swelled. When the system was brought to 20 ° C., the gel was further swollen and shown to respond independently to each stimulus.

[The invention's effect]
The stimulus-responsive material used in the present invention is different from conventional ones, and has multi-functionality that responds independently to multi-stimulations, which can contribute to high performance of various mechanochemical materials and actuators.

Claims (4)

  Utilizing a material having a block or graft copolymer represented by the general formula AmBn (m, n is an integer of 1 to 5) composed of a polymer chain A and a polymer chain B having different solubility parameters as a main constituent, at least A stimulus-responsive material characterized in that the affinity with a biological component and / or a drug is changed by changing the amount of space in length, area, or volume independently for two or more stimulation conditions. How to Use.   The use method according to claim 1, wherein at least a temperature change and / or a pH change is included in the two or more stimuli.   3. The utilization method according to claim 1, wherein the stimulation response utilization method separates and purifies the biological component and / or the drug.   The method of using a stimulus response according to claim 1 or 2, wherein the method of using a stimulus response cultures cells.