JP2685792B2 - Novel cross-linked copolymer, its gel and its structure - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial field of application) The present invention is applied to a patch electrode for an electrocardiograph, a patch electrode for a low-frequency therapeutic device, an ultrasonic transmission medium for ultrasonic diagnosis, and a hydrous patch such as a poultice. Novel cross-linked copolymer, its gel and its structure.

(Prior Art) Conventionally, as a biomedical electrode, a method using a natural water-soluble polymer such as gelatin has been known (Japanese Patent Publication No. 50-27).
317), or as a method of using a synthetic polymer therein, a hydrophilic polymer containing a salt of a carboxylic acid and containing at least 5 mol% of a monomer unit may be used (JP-A-56).
-36939), an electrode material obtained by polymerizing a precursor consisting of a water-soluble polyhydric alcohol, an ionic unsaturated material, a polyfunctional unsaturated material and a free radical initiator on an electrode plate No. -500003) is also known. Further, the present inventors obtained by polymerizing and crosslinking an ionic unsaturated monomer, a trialkoxyalkyl (meth) acrylate, a polyalkylene glycol (meth) acrylate, and a water-soluble polyhydric alcohol in the presence of water. We have found that the obtained conductive adhesive is excellent for biomedical electrodes, and have already applied for it. (Japanese Patent Laid-Open No. 61-268767) (Problems to be solved by the invention) However, when natural water-soluble polymers are used, the quality is not stable because they are natural products, and contamination and impurities due to contaminants Deterioration occurs due to. On the other hand, when a synthetic polymer is used, it does not have the above-mentioned drawbacks. However, in the prior art, polyhydric alcohols such as glycerin are often used for the purpose of moisturizing, and the presence of these polyhydric alcohols provides a suitable place for the reproduction of molds. Not only is it a problem with synthetic polymers, but it has been necessary to use antifungal agents and the like. In the case of polyacrylic acid and polyacrylic acid salt copolymers that have been mainly used in the past,
There is a problem that physical properties such as water absorption and cohesiveness change due to PH etc., for example, when trying to contain a drug etc. inside, the property changes due to that drug, or the reaction or interaction between the copolymer and drug There was a problem of causing. Further, in JP-A-61-268767, there are cases where mold does not occur, but there are cases where the tackiness changes during a long period of time.

(Means for Solving the Problems) The present invention has an object to provide a hydrophilic and water-insoluble novel cross-linked copolymer which is excellent in water retention, cohesiveness, antibacterial property, and is not affected by PH. The object is to provide a gel comprising the novel cross-linked copolymer, its structure and the like.

The above object of the present invention is to Alkali metal salt unit of sulfoalkyl methacrylate (hereinafter abbreviated as A unit) represented by more than 15% by weight 7
9.8% by weight or less, 2-hydroxyalkynolemethacrylate unit (hereinafter abbreviated as B unit) of 20 wt% or more and less than 84.8 wt% and A novel cross-linked copolymer consisting of 0.2 to 5% by weight of a polyethylene glycol ditammethacrylate unit (hereinafter abbreviated as C unit) represented by (wherein R ₁ is —CH ₂ —CH ₂ — or —
CH ₂ —CH ₂ —CH ₂ — and R ₂ is —CH ₂ —CH ₂ — or In and, R ₃ is _{CH 2 -CH 2 O n CH 2} -CH 2 - [n = 0 to 22]
And M is Na or K. ), And a gel comprising the above novel cross-linked copolymer, water and a polyhydric alcohol having 6 or less carbon atoms, and further a structure in which the gel is reinforced with a non-woven fabric or laminated with a film or the like. To be done.

The present invention relates to a novel crosslinked copolymer composed of A unit, B unit and C unit. The structural units will be described below.

First, the alkali metal salt of sulfoalkyl methacrylate constituting the A unit is a compound having a structure in which a sulfonic acid group of a methacrylic acid ester of an aliphatic alcohol having a sulfonic acid group is neutralized with alkali, and 2-sulfoethyl methacrylate or The sodium salt or potassium salt of 3-sulfopropyl methacrylate is preferably used. These monomers are salts of strong acids and strong bases,
Since it has a neutralized structure, it has strong hydrophilicity, and it is characterized by being hard to interact with other additives and drugs. Further, since it has an appropriately long alkyl group, it is presumed that the glass transition point is not so high even though it is a salt, and it gives the polymer relatively flexible properties. The 2-hydroxyalkyl methacrylate constituting the B unit has been conventionally used as a raw material for a water-insoluble, hydrophilic copolymer, but in the present invention, it is used for the purpose of further enhancing hydrophilicity. Copolymerized with an alkali metal salt of methacrylate. Further, as the monomer constituting the C unit, there are polyethylene glycol dimethacrylate, diethylene glycol dimethacrylate, triethylene glycol dimethacrylate, tetraethylene glycol dimethacrylate, and polyethylene glycol dimethacrylate (n = 9,14,23, etc.). Any of these can be preferably used, but when tetraethylene glycol dimethacrylate is used, a particularly good feeling can be obtained. The proportion of each component in the crosslinked copolymer of the present invention is preferably adjusted appropriately according to the purpose of use, but the A unit is
More than 15% by weight and 79.8% by weight or less, B unit is 20% by weight or more and less than 84.8% by weight, and C unit is 0.2 to 5% by weight. The crosslinked copolymer of the present invention can be particularly usefully used as a gel containing water and a polyhydric alcohol having 6 or less carbon atoms.

In the present invention, as the polyhydric alcohol having 6 or less carbon atoms, for example, ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, glycerin, diglycerin, 2,3-butanediol, 1,2- Butanediol, 1,3
-Butanediol, 3-methyl-1,3-butanediol,
3-methyl 1,3,5-pentanetriol and the like.

The mixing ratio of the cross-linked copolymer and water and glycerin in the gel of the present invention must be appropriately determined according to the desired physical properties (for example, flexibility, adhesiveness, electric conductivity, etc.). Is 20-40% by weight of the gel, preferably 25-35% by weight, water 5-50% by weight, preferably 15-40%
% By weight, and the polyhydric alcohol is selected from the range of 25 to 70% by weight, preferably 30 to 60% by weight.

The gel of the present invention has physical properties suitable for use as a gel alone depending on the composition and morphology of the copolymer, but depending on the composition and morphology, it has strong tackiness, or is soft and thin and has good morphological stability. It may not be.
In such a case, in order to improve the morphological stability, a reinforcing material such as a non-woven fabric, a woven fabric, or a knitted fabric is put in the gel to reinforce it into a sheet-like product, or by laminating it with a film or a cloth. The structure can be put to practical use. If necessary, an electrolyte such as salt, a coloring agent such as a dye or a pigment, and a drug such as an analgesic may be mixed in the gel, the structure or the like.

The cross-linked copolymer of the present invention is obtained by polymerizing the constituent monomers. Since the cross-linked copolymer of the present invention is insoluble in various solvents, it is polymerized in dissolution to dissolve the monomer to obtain a gel-like product, and then the solvent is removed by an operation such as extraction or heating to remove the solvent. Can be separated. Since the monomer constituting the cross-linked copolymer of the present invention is easily radically polymerized, a method of heating in the presence of a thermal polymerization catalyst such as azobisisobutyronitrile, benzoyl peroxide, lauroyl peroxide, benzoin alkyl A usual radical polymerization method such as a method of irradiating with ultraviolet light in the presence of a photopolymerization initiator such as ether or benzophenone 1-hydroxycyclohexyl phenyl ketone, a method of using both of them together is used. The gel, which is an important aspect of the present invention, can also be obtained by swelling the crosslinked copolymer isolated as described above with a mixed solution of water and a polyhydric alcohol. A gel having a desired shape can be obtained by placing a mixture of a polyhydric alcohol having 6 or less carbon atoms and water in a container having a desired shape and polymerizing the mixture. According to such a method, in addition to the advantage that the gel can be obtained in one step, since the polymerization proceeds in a uniform state from the beginning, a gel having a transparent and beautiful appearance can be obtained. Further, in order to obtain a sheet-like material containing a reinforcing agent, a laminate with a film, cloth or the like, a mixture of raw material monomers, water, polyhydric alcohol, etc. and a non-woven fabric, woven fabric, knitted fabric, film, fabric, etc. can be used in a desired form. Then, the desired structure can be easily obtained by polymerizing.

〔Example〕

Hereinafter, the present invention will be described in more detail with reference to Examples.

Example 1 15 parts by weight of a potassium salt of 3-sulfopropyl methacrylate (hereinafter abbreviated as SPM) was dissolved in 17.5 parts by weight of water to prepare an SPM aqueous solution. 0.1 parts by weight of 1-hydroxycyclohexyl phenyl ketone and 0.4 parts by weight of tetraethylene glycol dimethacrylate were dissolved in 15 parts by weight of 2-hydroxyethyl methacrylate, and this solution was added to the above solution.
Mixed with SPM aqueous solution. This mixture was placed horizontally in a dish that had a thickness of 1 mm, and it was placed 15 cm below the 30 W (tube length 53 cm) chemical lamp (Toshiba FL30SBL).
Was placed, and after nitrogen substitution, polymerization was carried out by irradiating with ultraviolet rays for 10 minutes to obtain a hydrous gel. 80 this gel
When dried in an oven at ℃ for 3 days, a glassy polymer was obtained. When this was immersed in water, it swelled but did not dissolve. From this, it is clear that the present polymer is a cross-linked copolymer. Further, when this polymer was pulverized and an infrared spectrum was taken by the KBγ tablet method, a spectrum as shown in Fig. 1 was obtained. That is, the absorption at 3400 cm ^-1 indicates the presence of OH based on 2-hydroxyethyl methacrylate, and the broad absorption near 1150 cm ^-1 is
It shows the existence of SO ^- ₃ based on SPM.

Example 2 23.2 parts by weight of SPM and 0.8 parts by weight of sodium chloride were dissolved in 15.4 parts by weight of water to prepare an SPM aqueous solution. 0.1 parts by weight of 1-hydroxycyclohexyl phenyl ketone and 0.4 parts by weight of tetraethylene glycol dimethacrylate were dissolved in 8.8 parts by weight of 2-hydroxyethyl methacrylate containing 0.3% ethylene glycol dimethacrylate, and further mixed with 52.6 parts of glycerin. Add this mixture to the SPM
Mixing with the aqueous solution gave a monomer mixture. A polyester film having a surface treated with silicon was placed on a glass plate kept horizontal. A rayon non-woven fabric with a basis weight of 10 g / m ² cut into 3 cm x 5 cm is placed on this, and 2.6 g from above
The monomer of was dropped and spread to the size of the non-woven fabric with a glass rod. When UV rays were irradiated for 7 minutes in N ₂ atmosphere in the same manner as in Example 1, a water-containing gel having tackiness, softness, and morphological stability was obtained. This product was peeled off from the film and attached to an electrode plate made of a conductive rubber with an electric cord and attached to the skin. As a result, the water-containing gel was able to hold it appropriately on the skin. When the cord was contacted with a low frequency treatment device and electricity was applied, it was found to have good conductivity. The gel was used once a day for about 10 minutes for 1 week and then hung in a room for 3 months, but no mold was found. Moreover, although there was a stain due to use and a decrease in the tackiness due to the stain, no change in physical properties was observed upon standing.

Example 3 15 parts by weight of SPM and 0.8 parts by weight of sodium chloride were dissolved in 17.5 parts by weight of water to prepare an SPM aqueous solution. 0.1 parts by weight of 1-hydroxycyclohexyl phenyl ketone, 0.4 parts by weight of tetraethylene glycol dimethacrylate, 0.42 parts by weight of fluorescent dye Fluorescent Orange, 0.1 parts by weight of ethylene glycol dimethacrylate and 15 parts by weight of 2-hydroxyethyl methacrylate and glycerin 52.5 Mixed with parts by weight. This mixed liquid was mixed with the SPM aqueous solution to form a monomer mixture. A polyester film having a surface treated with silicon was placed on a glass plate kept horizontal. Place a piece of gauze cut into 3 cm × 5 cm on this, 2.6 g from above
Was added dropwise to spread the liquid in the form of gauze. When ultraviolet rays were irradiated for 7 minutes in N ₂ atmosphere in the same manner as in Example 1, a sticky, fluorescent pinkish orange hydrogel was obtained. Since this product is colored, its appearance is beautiful, and it has excellent performance for a low-frequency treatment device as in Example 3, and no generation of mold was observed.

Example 4 22.5 parts by weight of a sodium salt of 2-sulfoethyl methacrylate (hereinafter abbreviated as SEM) was dissolved in 37.5 parts by weight of water to obtain an SEM aqueous solution. 0.1 parts by weight of 1-hydroxycyclohexyl phenyl ketone, 5 parts by weight of polyethylene glycol dimethacrylate (n = 23), 1 part by weight of methyl salicylate, 17.5 parts by weight of 2-hydroxyethyl methacrylate and 0.08 parts by weight of ethylene glycol dimethacrylate are mixed, A homogeneous solution was prepared and further mixed with diglycerin. This solution was uniformly mixed with the above SEM aqueous solution to obtain a monomer mixed solution. A 25 μm-thick polyester film was placed horizontally, and the monomer mixture was coated with a bar coater to a thickness of 150 μm. When ultraviolet rays were irradiated for 7 minutes in N ₂ atmosphere in the same manner as in Example 1, a transparent and tacky film / hydrogel laminate was obtained. When the gel layer was extracted with methanol and analyzed by gas chromatography, it was found that the same amount of methyl salicylate as the charged amount was contained.

Example 5 A small amount of sulfuric acid was added to the SPM aqueous solution in Example 2 to obtain SPM.
The pH of the aqueous solution was reduced to 2. A hydrogel was obtained using this SPM in the same manner as in Example 2. The tackiness and cohesiveness of this gel were the same as those of the gel of Example 3, and no generation of mold or the like was observed. Two pieces of this gel attached to a stainless steel plate having a length of 60 mm and a length of 60 mm were attached to each other with their gels facing each other. LF Impedance Analyzer 41
When two stainless steel plates were connected to a 29A (Yokogawa Hewlett Packard) measurement cable and the impedance was measured at a frequency of 10 Hz, it was 97.2Ω (phase angle 59 °).
Met. On the other hand, when the same measurement was performed using the gel of Example 2, it was 186.3Ω (phase angle 63.4 °). By lowering the PH, almost without changing other physical properties,
The conductivity could be changed.

(Effect of the Invention) According to the present invention, it is possible to obtain a hydrophilic, water-insoluble crosslinked copolymer having stable quality, excellent in antifungal properties, and stable over time, and having little physical property change due to PH. A hydrogel using this crosslinked copolymer and a structure using the hydrogel can be obtained.

[Brief description of the drawings]

FIG. 1 shows the infrared spectrum of the novel crosslinked copolymer of the present invention obtained in Example 2.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Office reference number FI technical display location C08L 33/14 C08L 33/14 // B32B 15/08 B32B 15/08 Q (C08F 220/38 220 : 28 220: 20) (C08F 220/28 220: 38 220: 20)

Claims (3)

(57) [Claims] (1) Alkali metal salt unit of sulfoalkyl methacrylate represented by more than 15 wt% and 79.8 wt% or less, 20 wt% or more and less than 84.8 wt% of the 2-hydroxyalkyl methacrylate unit represented by A novel cross-linked copolymer consisting of 0.2 to 5% by weight of polyethylene glycol dimethacrylate unit represented by: (Wherein, R ₁ is -CH ₂ -CH ₂ - or -CH ₂ -CH ₂ -CH ₂ -
And R ₂ is —CH ₂ —CH ₂ — or In and, R ₃ is _{CH 2 -CH 2 O n CH 2} -CH 2 - [n = 0 to 22]
And M is Na or K. ) 2. A gel comprising the novel crosslinked copolymer according to claim 1, water and a polyhydric alcohol having 6 or less carbon atoms. 3. A gel structure in which the gel according to claim 2 is reinforced with a non-woven fabric, a woven fabric or a knitted fabric, or laminated with a film or a fabric.