Patent Description:
Poly(N-isopropylacrylamide) [poly(NIPAAm)] is known to be a typical example of a temperature-responsive polymer. Poly(NIPAAm) exhibits a lower critical solution temperature (LCST), which is a phenomenon in which solubility in an aqueous solution is exhibited at lower temperatures while precipitation (phase separation) occurs at higher temperatures.

A volume phase transition is also known to occur with poly(NIPAAm) hydrogels. Application to drug delivery systems utilizing this property has been proposed (PTL <NUM>).

Examples of thermo-responsible hydrogels are described in NPL1 and NPL <NUM>.

Other examples of hydrogels containing a metal salt of an organic acid are described in NPL3, PTL2, PTL3, and PTL <NUM>.

In NPL <NUM> is described a self-assembly formed by "net-like" bridges of the carboxylic acid of a polyacrylic polymer with the calcium ions of an aqueous solution of calcium acetate.

While applications that use the volume phase transition are interesting, a problem has been that, depending on the application, the use of materials that undergo a change in dimensions may be infeasible, for example, in the case of use for a structural material.

The present invention therefore addresses the problem of providing a temperature-responsive gel having an LCST that does not exhibit a volume phase transition, and a method for producing same.

The present invention can provide a temperature-responsive gel that has an LCST without a volume phase transition.

The following properties are exhibited by the gel that has a chemically crosslinked structure (due to a crosslinking agent), which is according to the present invention. (<NUM>) With regard to the temperature responsiveness, for both an increasing temperature and a declining temperature, the response is faster than for a gel having a physically crosslinked structure.

The following properties are exhibited by the gel that has a physically crosslinked structure (not due to a crosslinking agent), not according to the present invention.

The present invention relates to a temperature-responsive hydrogel that comprises a carboxyl group-bearing polymer and a divalent metal salt of an organic acid.

The carboxyl group-bearing polymer is a copolymer of a plurality of monomer species that includes such a monomer.

The carboxyl group-bearing monomer can be exemplified by α,β-unsaturated carboxylic acids that contain one or two or more carboxyl groups in the molecule. Such α,β-unsaturated carboxylic acids can be exemplified by acrylic acid, methacrylic acid, itaconic acid, maleic acid, maleic anhydride, aconitic acid, fumaric acid, and crotonic acid.

The copolymer can be a copolymer of a plurality of carboxyl group-bearing monomer species or can be a copolymer of carboxyl group-bearing monomer and monomer other than carboxyl group-bearing monomer. There are no particular limitations on the monomer constituting the copolymer other than the carboxyl group-bearing monomer, and the former can be exemplified by at least one selected from the group consisting of acrylate monomers (for example, esters of α,β-ethylenically unsaturated carboxylic acids, hydroxyalkyl esters of α,β-ethylenically unsaturated carboxylic acids, and alkoxyalkyl esters of α,β-ethylenically unsaturated carboxylic acids), acrylamide monomers, and styrenic monomers.

The aforementioned acrylate monomers are not particularly limited and can be exemplified by esters of α,β-ethylenically unsaturated carboxylic acids, e.g., methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, n-propyl acrylate, n-propyl methacrylate, isopropyl acrylate, isopropyl methacrylate, lauryl acrylate, and stearyl acrylate; hydroxyalkyl esters of α,β-ethylenically unsaturated carboxylic acids, e.g., <NUM>-hydroxyethyl acrylate, <NUM>-hydroxyethyl methacrylate, and <NUM>-hydroxypropyl methacrylate; and alkoxyalkyl esters of α,β-ethylenically unsaturated carboxylic acids, e.g., diethylene glycol methacrylate.

The aforementioned acrylamide monomers are not particularly limited and can be exemplified by acrylamide and methylolmethacrylamide.

The aforementioned styrenic monomer is not particularly limited and can be exemplified by styrene and alkylstyrenes.

In the copolymer preferably equal to or more than <NUM>% as a molar ratio is derived from carboxyl group-bearing monomer from the standpoint of exhibiting the temperature responsiveness that is a characteristic of the hydrogel according to the present invention. A copolymer for which preferably equal to or more than <NUM>%, more preferably equal to or more than <NUM>%, still more preferably equal to or more than <NUM>%, and most preferably equal to or more than <NUM>%, as a molar ratio, is derived from carboxyl group-bearing monomer is advantageous.

From the standpoint of exhibiting the temperature responsiveness that is a characteristic of the hydrogel according to the present invention, the carboxyl group content in the polymer is, for example, suitably in the range from <NUM> to <NUM> mol/g and is preferably in the range from <NUM> to <NUM> mol/g and more preferably in the range from <NUM> to <NUM> mol/g.

According to the present invention, the group-bearing polymer has a chemically crosslinked structure. The chemically crosslinked structure can be formed by crosslinking with a crosslinking agent during polymer formation or after polymer formation.

A di-functional or more multi-functional monomer is used as the crosslinking agent used to form a chemically crosslinked structure. This crosslinking agent can be exemplified by N,N'-methylenebisacrylamide (MbAAd), N,N'ethylenebisacrylamide, diethylene glycol diacrylate, diethylene glycol dimethacrylate, polyethylene glycol diacrylate, polyethylene glycol dimethacrylate, and <NUM>-acryloyloxy-<NUM>-methacryloyloxy-<NUM>-propanol. The amount of the crosslinking agent can be in the range, for example, from <NUM> to <NUM> mol% with reference to the monomer concentration in conformity with the desired degree of crosslinking.

The mass-average molecular weight of the polymer is not particularly limited, but may be, for example, equal to or less than <NUM>,<NUM>,<NUM> and is more preferably equal to or less than <NUM>,<NUM>. The lower limit may be, for example, equal to or more than <NUM>,<NUM> and is preferably equal to or more than <NUM>,<NUM>. However, it may not actually be possible to measure the average molecular weight of the polymer having a crosslinked structure.

A physically crosslinked structure is formed by the formation of a salt between two carboxyl groups possessed by the polymer and one divalent metal and/or by polymer entanglement. The former physically crosslinked structure is formed by the formation of a salt by the divalent metal in polymer that has been formed without using a crosslinking agent. A phenomenon wherein the physically cut hydrogel undergoes re-unification after cutting is due mainly to salt formation between the carboxyl groups and divalent metal. However, it is hypothesized that polymer entanglement also proceeds with the passage of a relatively long period of time and further strengthens the re-unification due to salt formation. The hydrogel according to the present invention having a chemical crosslinked structure may also have a physically crosslinked structure due to salt formation between one divalent metal and two carboxyl groups possessed by the polymer and also due to the presence of polymer entanglement.

The polymerization method used to prepare the polymer is exemplified by radical polymerization using a thermal initiator (thermal polymerization) and by photopolymerization using a photoinitiator. Photopolymerization is preferred. Known initiators may be used as appropriate as the polymerization initiator. The photoinitiator can be, for example, α-ketoglutaric acid. The initiator can be, for example, in the range from <NUM> to <NUM> mol% with reference to the monomer concentration.

According to the present invention, the organic acid is at least one organic acid selected from the group consisting of formic acid, acetic acid, and propionic acid based on a consideration of the solubility curve and solubility in aqueous solution of the salt in the hydrogel. For example, in the range from <NUM> to <NUM>, calcium formate exhibits for its relationship with temperature a relatively modestly positive solubility curve (the solubility rises when the temperature rises). In contrast to this, for its relationship with temperature, calcium acetate exhibits a negative solubility curve in the range from <NUM> to approximately <NUM> and exhibits a relatively modestly positive solubility curve in the range from approximately <NUM> to approximately <NUM>. For its relationship with temperature, calcium propionate exhibits a negative solubility curve in the range from <NUM> to approximately <NUM> and a positive solubility curve in the range from approximately <NUM> to <NUM>.

The divalent metal constituting the divalent metal salt of the organic acid specified above is calcium (Ca).

According to the present invention, the divalent metal salt of the organic acid is at least one selected from the group consisting of Ca formate, Ca acetate, and Ca propionate. According to the present invention, the concentration of an aqueous solution of the divalent metal salt of the organic acid impregnated in the polymer in the range from <NUM> to <NUM>. The LCST of the hydrogel can be varied using the concentration of the divalent metal salt of the organic acid contained in the polymer. The concentration of the divalent metal in the polymer tends to be higher than the divalent metal concentration in the aqueous solution of divalent metal salt of an organic acid that is impregnated in the polymer, and varies with conditions such as the carboxyl group concentration in the polymer, the concentration of the divalent metal salt of an organic acid in the aqueous solution, and so forth, and may be, for example, a concentration that is approximately <NUM>- to <NUM>-times and more typically approximately <NUM>- to <NUM>-times higher. When the divalent metal is calcium, the divalent metal concentration in the polymer is, for example, in the range from approximately <NUM> to <NUM> in <NUM> of polymer (gel), and more typically can be in the range from <NUM> to <NUM> and even more typically can be in the range from approximately <NUM> to <NUM>.

The total metal ion concentration in the polymer can be measured, for example, using inductively coupled plasma atomic emission analysis (ICP). A known volume of the polymer is incinerated (for example, at approximately <NUM>) to remove the organic component; the residue is dissolved in a known volume of water; and the metal ion concentration can be determined by submitting this aqueous solution to measurement by ICP. The concentration in the polymer of free metal ion, which does not participate in formation of the organic acid salt, can be measured, for example, using a metal ion electrode. When metal ion forming the organic acid salt and free metal ion are present in the polymer, the two can be discriminated using this method.

The present invention relates to a hydrogel, wherein a hydrogel is a gel for which the main constituent components are a polymer and water or an aqueous solution. Whether or not the polymer forms a hydrogel can be determined mainly by the length of the polymer (in other words, the concentration of the polymerization initiator). For the same polymer mass, the tendency to undergo gelation increases at a higher polymerization initiator concentration. From this standpoint, for the case, for example, of acrylic acid as the monomer, gelation tends to occur at equal to or higher than <NUM> when the polymerization initiator concentration is <NUM> mol% and at equal to or higher than <NUM> when the polymerization initiator concentration is <NUM> mol%. This is about the same when the monomer is methacrylic acid. The polymerization initiator concentration can be suitably selected in the hydrogel formation range, in conformity with the type of polymerization initiator and the type of monomer.

The temperature-responsive hydrogel according to the present invention has a lower critical solution temperature (LCST). The LCST is the lower critical solution temperature where the hydrogel develops turbidity due to phase separation, and is an indicator of the phase separation temperature. The presence of an LCST can be evaluated, for example, by measurement of the turbidity (transmittance) using an ultraviolet-visible-near infrared spectrophotometer. This evaluation can also be performed by endo-/exothermic peak measurement by differential scanning calorimetry. This evaluation can also be performed by measurement of the temperature dependence of the dynamic elastic modulus using a rheometer (viscoelastic measurement instrument). The LCST of the temperature-responsive hydrogel according to the present invention, while varying with the composition of the polymer and the type and concentration of the divalent metal salt of an organic acid, is, for example, in the range from <NUM> to <NUM> and is preferably in the range from <NUM> to <NUM>.

The temperature-responsive hydrogel according to the present invention is transparent at a temperature below the LCST and is in a turbid state at a temperature above the LCST. In the present invention, transparent denotes a transmittance at a wavelength of <NUM> of equal to or more than <NUM>%, while a turbid state denotes a transmittance at a wavelength of <NUM> of equal to or less than <NUM>%.

The present invention encompasses a method for producing a temperature-responsive hydrogel, wherein the method includes immersing a carboxyl group-bearing polymer having a chemically crosslinked structure formed by a crosslinking agent, which is a di-functional or more monomer in an aqueous solution of a divalent metal salt of an organic acid, wherein the divalent metal is an alkaline-earth metal calcium, wherein the carboxyl group-bearing polymer is a copolymer of a plurality of monomer species that includes the carboxyl group-bearing monomer, wherein the organic acid is at least one organic acid selected from the group consisting of formic acid, acetic acid, and propionic acid and wherein the concentration of the divalent metal salt of the organic acid in the aqueous solution is in the range from <NUM> to <NUM>.

The carboxyl group-bearing polymer and the divalent metal salt of an organic acid are the same as described above with reference to the temperature-responsive hydrogel according to the present invention. Immersion of the polymer in the aqueous solution of divalent metal salt of an organic acid can be performed at normal temperatures, for example, at a temperature in the range from <NUM> to <NUM>. However, it can be performed at a temperature higher than or at a temperature lower than the LCST in terms of the LCST of the obtained temperature-responsive hydrogel.

The concentration of the divalent metal salt of an organic acid in the aqueous solution of the divalent metal salt of an organic acid may be determined as appropriate considering the type of polymer, type of divalent metal salt of an organic acid, and desired LCST, and, is in the range from <NUM> to <NUM>. For example, the temperature-responsive hydrogel according to the present invention can be obtained by immersion, until an approximate equilibrium is reached. regard to the immersion time, in the case of a chemically crosslinked gel, which is according to the present invention, for example, an approximate equilibrium is reached at about <NUM> to <NUM> hours, and in the case of a physically crosslinked gel, which is not according to the present invention, an approximate equilibrium is reached in <NUM> to <NUM> days. However, immersion until reaching equilibrium may also be unnecessary as long as the desired properties are obtained.

A temperature-responsive hydrogel according to the present invention as described above can be produced by the production method according to the present invention.

The temperature-responsive hydrogel according to the present invention has the following properties.

The following properties are exhibited by the gel that has a chemically crosslinked structure (due to a crosslinking agent), which is according to the present invention. (<NUM>) With regard to the temperature responsiveness, the response is fast at both an increasing temperature and a declining temperature.

The following properties are exhibited by the gel that has a physically crosslinked structure (not due to a crosslinking agent), which is not according of the present invention.

The density of the hydrogel according to the present invention can be controlled and varied through the charge concentration of the monomer and the use/nonuse of a crosslinking agent. For example, in the case of a hydrogel with a physically crosslinked structure obtained without the use of a crosslinking agent, and for acrylic acid as the monomer, the density of the hydrogel obtained at an acrylic acid monomer charge concentration of <NUM> is approximately <NUM>/cm<NUM> (molecular weight of AAc = <NUM>, <NUM> = <NUM>/<NUM> ≈ <NUM>/cm<NUM>).

The temperature-responsive hydrogel according to the present invention exhibits the properties indicated above and can be deployed in a variety of applications. For example, it can be used as a temperature-responsive structural material, as a temperature-responsive scaffolding material for cell culture, and as a temperature-responsive porous material, in each case for which the dimensions thereof do not change with temperature. However, there is no limitation to the preceding.

The present invention is more particularly described in the following based on examples. However, the examples are illustrations of the present invention, and there is no intent for the present invention to be limited to or by the examples.

A diagram that outlines a method for producing the temperature-responsive hydrogel according to the present invention is given in <FIG>. A precursor aqueous solution is prepared by dissolving the following in ultrapure water: carboxyl group-bearing monomer (typically acrylic acid (AAc) or methacrylic acid (MAAc)) in the range from <NUM> to <NUM>, the initiator α-ketoglutaric acid in the range from <NUM> to <NUM> mol% with reference to the monomer concentration, and the crosslinking agent N,N'-methylenebisacrylamide (MbAAd) in the range from <NUM> to <NUM> mol% with reference to the monomer concentration. Here, a physically crosslinked gel, which is not according to the present invention, is obtained at a crosslinking agent concentration of <NUM> mol%, while a chemically crosslinked gel, which is according to the present invention, is obtained when the crosslinking agent is added.

This solution is poured into a form with a freely selected shape, and a gel is formed by polymerizing for equal to or more than <NUM> hours under exposure to ultraviolet radiation at a wavelength of <NUM> in an argon gas atmosphere. A sample is obtained by immersing, until equilibrium is reached, the polymerized gel or nonflowable high-viscosity material in a sufficient amount of an aqueous solution which is prepared by dissolving a salt formed of a carboxylic selected from formic acid, acetic acid, or propionic acid and calcium as divalent cation (typically calcium acetate) in ultrapure water at a concentration in a range from <NUM> to the saturation concentration.

Volume measurement: before and after phase transition, the thickness and diameter are measured three times on the gel molded on a disk, and the average thereof and deviation are calculated.

Measurement of the LCST temperature: this was determined from the turbidity using an ultraviolet-visible-infrared spectrophotometer. The sample and soaking salt solution were introduced into a quartz cell and the absorbance was measured at a fixed wavelength of <NUM> while raising the temperature/lowering the temperature at a constant heating/cooling rate (<NUM>/min) in the range from <NUM> to <NUM>.

Two samples, i.e., before phase transition and after phase transition, were quickly sandwiched with copper blocks that had been thoroughly cooled in advance with liquid nitrogen (-<NUM>) and the structure was frozen by rapid freezing; this was followed by drying of the gel by freeze drying. Using a scanning electron microscope, observation was carried out on the cross section exposed by cutting the dried sample.

Using a tensile tester, tensile testing was performed in the salt solution soaking the test specimen, which had been molded in a dumbbell shape. The temperature of the salt solution was adjusted using a water bath. After holding long enough to make the temperature uniform, pulling was carried out at a speed in the range from <NUM> to <NUM>/min and the stress-strain curve was obtained from the initial dimensions of the sample. The Young's modulus was determined from the initial slope; the fracture stress and fracture strain were determined when fracture occurred; and the toughness was determined from the area of the stress-strain curve.

Evaluation of self-healing: after the aforementioned mechanical testing had been performed, the tensile test was run a second time on the same sample after the sample had been submitted to different waiting times. The percentage between the area of the obtained stress-strain curve and the area for the first time was determined to give the recovery percentage.

The volume and mass of a hydrogel sample were measured, following by incineration of the hydrogel sample at approximately <NUM> to remove the organic component. The residue was dissolved in a known amount of water, and the total metal ion concentration in the polymer was measured by inductively coupled plasma atomic emission analysis (ICP) using the resulting aqueous solution. The metal ion concentration in the hydrogel sample was calculated from the measurement results (for example, number of moles or mass of metal ion in <NUM>).

The example of a chemically crosslinked hydrogel is given.

<FIG> shows the appearance (transparent and turbid) at a temperature (room temperature) below the LCST and at a temperature (<NUM>) above the LCST, and the volume change for room temperature and <NUM>. It is demonstrated that the volume change is almost nonexistent and is constant.

The results of measurement of the LCST are shown in <FIG>. The LCST for each system is shown in <FIG>. The LCST is shown to change due to a change in the organic acid in the organic acid salt.

<FIG> shows the change in volume with ionic species at room temperature and <NUM>. It is shown that the volume substantially does not change regardless of the ionic species.

<FIG> gives photographs of the surface state of the gel at room temperature and <NUM>. The structural principle (reason) is demonstrated whereby the hydrogel according to the present invention has a constant volume with respect to temperature changes.

MgAc (not according to the present invention), NaAc (not according to the present invention), AlAc (not according to the present invention), CaCl<NUM> (not according to the present invention), MaSO<NUM> (not according to the present invention), each at <NUM>.

The results are given in <FIG>. An LCST was exhibited for the two cases of calcium acetate and magnesium acetate (the effect for magnesium acetate was smaller than for calcium acetate). An LCST was not exhibited by the chloride salt or sulfate salt. Based on these results, it is shown that, in order to obtain a hydrogel that exhibits an LCST, the metal must be a divalent metal (cation) and a combination with an organic acid (preferably acetic acid) ion is required for the counteranion.

The results are given in <FIG>. An LCST was exhibited with polyacrylic acid and polymethacrylic acid. An LCST was not exhibited, on the other hand, by PAMPS. These results demonstrate that a carboxyl group-bearing polymer is required for the exhibition of an LCST.

Organic acid salt: CaAc (according to the present invention), MgAc (not according of the present invention).

The results are given in <FIG> and <FIG>. The LCST is shown to have a minimum value depending on the salt concentration. For PAAc-MgAc in <FIG> and PMAAc-CaAc in <FIG>, it is shown that the LCST declines when the salt concentration is raised, while at higher concentrations the LCST increases.

The example of a physically crosslinked (without MbAAd) hydrogel is given.

The LCST was measured at different copolymerization ratios between AAc, which exhibits an LCST, and acrylamide (AAm), which does not exhibit an LCST. The results are given in <FIG>. At higher AAc concentrations, the LCST is lower and a phase separation structure is more readily produced. It is shown that gelation does not occur when the AAm concentration exceeds <NUM>%.

The example of a chemically crosslinked hydrogel (LCST = <NUM>) is given. <FIG> gives the results of tensile mechanical testing for measurement temperatures of <NUM>, <NUM>, <NUM>, and <NUM>. At <NUM>, which is equal to or above the LCST, a high strength and high toughness are obtained and the elastic modulus and toughness both increase with an increase in temperature. At a higher temperature of <NUM>, it is shown that the elastic modulus is sharply higher (becomes very hard) and the toughness is reduced. Photographs of the test specimen at <NUM> and <NUM> are given in <FIG>.

The example of a physically crosslinked hydrogel is given.

The results of measurement of the LCST are given in <FIG>. (During cooling, complete recovery was eventually obtained, but very slowly.

The volume change at <NUM> and <NUM> is given in <FIG>. It is shown that there is almost no volume change.

The results of tensile mechanical testing at <NUM>, <NUM>, and <NUM> are given in <FIG>. It is shown that, at or above the LCST, the strength and toughness are sharply increased, while at a higher temperature the strength is ultrahigh while the toughness declines.

The results of self-healing testing are given in <FIG>. There is an approximately <NUM>% recovery at <NUM> hours, and it is thought that complete recovery will finally occur.

The Ca concentration (measured by ICP) in the hydrogel is as follows.

<FIG> provides photographs that show the timewise change in physiological saline (<NUM>) of a test specimen of the physically crosslinked hydrogel (LCST = <NUM>) prepared using the aforementioned <NUM> PAAc - <NUM> CaAc condition. It is shown that this hydrogel dissolves in physiological saline with elapsed time.

The LCST was measured using differential scanning calorimetry (DSC). A small amount of the sample (several tens of milligrams) was introduced into an aluminum pan (container), which was sealed using a tool provided for this purpose. Using air for the reference sample, the temperature was raised from <NUM> to <NUM> at a ramp rate of <NUM>/min and the endothermic peak associated with phase separation was measured. <FIG> is the DSC profile for a typical polymer (<NUM> PAAc - <NUM> CaAc). The downward peak represents the heat absorption of the sample and corresponds to phase separation. The position of the LCST was determined from the intersection of the two straight lines for the curve segment where the endothermic peak begins.

<FIG> gives the LCSTs for various combinations of PAAc and CaAc concentrations. An increasing trend for the LCST was exhibited as the polymer concentration increased and as the calcium acetate concentration declined. An LCST was not observed in the measurement range for the white region in the lower right (<NUM> PAAc - <NUM> CaAc, <NUM> PAAc - <NUM> CaAc).

This gel exhibits a phenomenon wherein it abruptly hardens when the temperature is further increased. The temperature when this occurs is called the hardening temperature (HT). The HT was determined using rheometric measurements. Using an instant glue, one side of the gel, which had been molded with a diameter of <NUM>, was attached to the center of a stainless steel parallel plate (pressing horizontal tool) and the opposite side was also attached to a stainless steel rotary container. In order to prevent drying, the container was filled with an aqueous calcium acetate solution having the same concentration as that used for sample preparation. The ramp rate is <NUM>/min, the temperature range is from <NUM> to <NUM>, the angular velocity for the frequency of the applied shear is <NUM> rad/s, and the strain is <NUM>%. <FIG> is the rheometric profile for a typical polymer (<NUM> PAAc - <NUM> CaAc). G' is the storage modulus, which is the elastic component, and G" is the loss modulus, which is the viscous component. Tan δ, known as the loss tangent, is G"/G' and is an index that shows whether a material is elastic or viscous; higher values indicate viscousness. The temperature at the peak for tan δ (around <NUM> in the present case) was taken to be the HT.

The HTs for various combinations of PAAc and CaAc concentrations are collected in <FIG>. As for the LCST, the HT presents an increasing trend as the PAAc concentration increases and the CaAc concentration declines. The white region below <NUM> in the figure indicates samples for which hardening was not identified in the measurement temperature range.

The preceding LCSTs (<FIG>) and HTs (<FIG>) are collected into a single phase diagram in <FIG>. The horizontal axis is the calcium acetate concentration/polyacrylic acid concentration ratio, which means that the salt concentration declines or the polymer concentration increases as <NUM> is approached. In the diagram, the inverted filled triangle ▼ refers to the LCST, while the upright open triangle △ refers to the HT. This diagram shows that, unlike ordinary phaseseparated gels, the hydrogel forms three states depending on temperature, i.e., "soft and transparent", "soft and turbid", and "hard and turbid" considered from the low temperature side.

In accordance with the rheometric results in <FIG>, G' undergoes an abrupt increase pre-versus-post-HT, and this is a characteristic feature of the present gel. The extent of the increase in the elastic modulus in comparison to pre-phase separation was evaluated. <FIG> gives the ratio between the maximum value and minimum value of G' as determined by rheometry. It is shown that, depending on the composition, an at least <NUM>,<NUM>-fold hardening occurs at a maximum. On the other hand, for the samples where an LCST and HT were not observed (for example, <NUM> PAAc - <NUM>, and <NUM> PAAc - <NUM> CaAc), almost no change in the elastic modulus is recognized.

Utilizing the heat-hardening behavior that is a feature of the hydrogel according to the present invention, the performance as a heat-responsive protector was evaluated. The postulate is protection of the clothing and body from frictional heat caused by, for example, an individual being dragged along the road surface due to, for example, a motorcycle accident.

The evaluation was performed in this test with a composite material provided by the formation of a composite between the hydrogel according to the present invention and a glass fiber fabric (GF). The composite was fabricated as follows: the glass fiber fabric was preliminarily inserted in a reaction cell; hydrogel polymerization was carried out in this reaction cell; and a sample was obtained in which the glass fiber fabric was embedded in the gel provided by the polymerization. The composition of the gel is <NUM> AAc, <NUM> mol% MBAA, crosslinking agent, <NUM> mol% α-Keto, initiator. The glass fiber fabric is as follows: E-glass composition, surface density = <NUM>/m<NUM>, thickness = <NUM>, diameter per single glass fiber = <NUM>. <FIG> is a photograph of the fabricated sample. The following control samples were used for comparison: an "ampholyte gel (PA)-GF" composite material that is tougher than iron (<NPL>), and a "polyacrylamide (PAAm)-GF" composite material between GF and a general weak gel.

<FIG> is a schematic diagram of the test system. A seesaw is attached to a tow truck, and a test cart for installing the sample is attached to one end. The road surface side of the test cart has a protrusion near the center, to which the four sides of the composite material are attached using four screws. The cart has four auxiliary wheels at the four corners for posture maintenance. When the cart is on the road surface and the posture is maintained, only the sample surface is in contact with the road surface, while the auxiliary wheels are designed to float. Thus, all the load is applied to the sample when the posture is maintained.

The test sequence is as follows. First, the cart is lifted from the road surface by operating the seesaw. While in this state, the tow truck is driven to a speed of <NUM>/h (<NUM> mph). While holding this speed, the seesaw is lowered and the sample is pressed against the road surface and the friction test is started. After <NUM> seconds of test time, the seesaw is raised and the sample is separated from the road surface. The air temperature was <NUM> and the road surface temperature was <NUM>. The temperature decline by the sample after the test was recorded with a thermographic camera, and the temperature immediately after the friction test was determined from Newton's cooling formula, see below, in order to evaluate whether or not hardening due to the frictional heat had occurred.

<FIG> shows the appearance of the samples before and after the friction test. The composite material with the hydrogel of the present invention was white after the test, only small scratches were observed on the surface, and damage to the fiber and back surface was not seen. On the other hand, the PA-GF composite material was highly ruptured to the fiber level. The PAAm-GF appeared unbroken at first glance; however, the regions held by the screws tore at the instant of pressing against the road surface and the sample ended up separating from the test cart, and it was thus weaker.

In order to confirm whether the PAAc-GF had undergone heat hardening due to the frictional heat, the temperature of the sample surface immediately after the friction test was determined using Newton's cooling formula. <FIG> contains temperature maps of the sample surface provided by a thermographic camera and contains a graph of the temperature drop as determined therefrom. Newton's cooling formula was fit to this data for the temperature drop, and the temperature immediately after the friction test was determined by extrapolation to zero seconds.

Tt is the temperature at t seconds; T<NUM> is the temperature at zero seconds (start); Tair is the temperature of the medium (the temperature of the air in this case, air temperature = <NUM>); K is a constant composed of the heat transfer coefficient α, the sample area S, and the heat capacity C; and t is time.

Two points of the actually measured thermographic data were inserted and K and T<NUM> were determined from the simultaneous equations to give a surface temperature of <NUM> immediately after the friction test. This was higher than the HT (<NUM>) of the composition of this gel, which suggested that hardening had occurred due to the frictional heat.

The frictional heat resistance was evaluated from the tearing energy determined using a trouser tearing test. A pristine composite material sample prior to the friction test and a sample that had been subjected to the friction test were shaped to a width of <NUM>, a length of <NUM>, and cut length of <NUM> and were subjected to a tearing test with a material tester. Tearing test profiles are provided in <FIG>, and the tearing energy was determined from the area made by this tearing curve, the sample thickness, and the test length (length - cut length = <NUM>).

The Lthickness in the denominator is the sample thickness, the Lbulk is the test length, and the integral in the numerator is the area made by the x-axis and the curve yielded by the tearing test.

The tearing energies were as follows: <NUM> ± <NUM> kJ/m<NUM> for the pristine sample (prior to the friction test) of the composite of GF and hydrogel according to the present invention; <NUM> ± <NUM> kJ/m<NUM> for this sample after the friction test; <NUM> ± <NUM> kJ/m<NUM> for the comparative pristine PA-GF sample; and <NUM> ± <NUM> kJ/m<NUM> for this sample after the test. While the pre-test tearing energies were equal, the reduction post-test was shown to be much smaller for the hydrogel according to the present invention than for PA. <FIG> contains a graph in which these ratios are designated the frictional heat resistance. Close to <NUM>% of the structure remained undamaged for the GF-hydrogel according to the present invention, while only about <NUM>% remained with the PA-GF.

Claim 1:
A temperature-responsive hydrogel comprising a carboxyl group-bearing polymer and an aqueous solution of a divalent metal salt of an organic acid impregnated in the polymer, wherein the carboxyl group-bearing polymer is a copolymer of a plurality of monomer species that includes the carboxyl group-bearing monomer, wherein the carboxyl group-bearing polymer has a chemically crosslinked structure formed by a crosslinking agent which is a di-functional or more multi-functional monomer, wherein the divalent metal is calcium, wherein the organic acid is at least one organic acid selected from the group consisting of formic acid, acetic acid, and propionic acid and wherein the concentration of the divalent metal salt of the organic acid in the aqueous solution is in the range from <NUM> to <NUM>.