Method for reducing residual monomers in polymer compounds

Abstract

To provide means for efficiently removing or reducing residual monomers from a polymer compound containing the residual monomers and the like.SOLUTION: A method for reducing residual monomers includes introducing ozone gas into a solution of a polymer compound, which is a polymerized compound having a polymerizable unsaturated double bond. The ozone gas for introduction is preferably added to the solution of the polymer compound at a rate of 1-100 mg / min. An alternative technique for ozone gas introduction is to blow ozone gas into an organic solvent and add the resultant ozone-containing organic solvent into the solution of the polymer compound.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a method for reducing residual monomers in polymer compounds, and more particularly to a method for reducing residual monomers having polymerizable unsaturated double bonds. [Background technology]

[0002] Polymer compounds using compounds having polymerizable unsaturated double bonds, such as vinyl compounds and allyl compounds, as raw materials are used in various fields. Some of these polymer compounds are used on the human body or come into contact with the human body during processing, and the compounds contained in these polymer compounds, mainly consisting of trace amounts of unpolymerized monomers, can have adverse effects on the human body. Furthermore, the trace compounds contained in the polymer compounds can have adverse effects on the molecular weight, viscosity, stability, and other aspects of the polymer compounds.

[0003] Therefore, as methods for removing trace amounts of monomer contained in these polymer compounds, there have been proposed a method of mixing the polymer with a mixture of a solvent that dissolves the polymer and a non-solvent that dissolves the monomer but not the polymer, and eluting the unreacted monomer into this mixture (see, for example, Patent Document 1); a method of rotating a rotating shaft inside an evaporator and using the centrifugal force to suck up the polymer latex through a pipe arranged inside the evaporator and deposit it on the heat transfer surface of the evaporator, thereby removing the unreacted residual monomer (see, for example, Patent Document 2); a method of gradually adding a redox initiator to a polymer solution (see, for example, Patent Document 3); and a method characterized by introducing hydrogen gas into a solution of a polymer compound having a polymerizable unsaturated double bond (see, for example, Patent Document 4). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 5-310816 [Patent Document 2] Japanese Patent Application Laid-Open No. 2000-264915 [Patent Document 3] Special Publication No. 2001-516774 [Patent Document 4] Japanese Patent Application Laid-Open No. 2007-063352 Summary of the Invention [Problem to be solved by the invention]

[0005] However, these methods have problems in that the operations are complicated, it takes a long time to remove the remaining monomer, the working efficiency is low, and it is difficult to reduce the amount of the remaining monomer to a trace amount. The present invention has been made in view of the above-mentioned conventional techniques, and an object of the present invention is to provide a method for efficiently removing and reducing residual monomers from a polymer compound containing residual monomers and the like. [Means for solving the problem]

[0006] The present inventors have conducted research to solve this problem and have completed the invention described in detail below. The present invention is as follows. [1] A method for reducing residual monomers, comprising introducing ozone gas into a solution of a polymer compound obtained by polymerizing a compound having a polymerizable unsaturated double bond. [2] The method according to [1], wherein the ozone gas is introduced into the polymer compound solution at a rate of 1 to 100 mg / min. [3] The method for reducing ozone according to [1], wherein the ozone gas is blown into an organic solvent, and the resulting ozone-containing organic solvent is added to the solution of the polymer compound. [4] The method according to claim 3, wherein the ozone content in the organic solvent is 20 to 1,000 mg / L. [5] The method according to [3] or [4], wherein the ozone-containing organic solvent is added to the polymer compound solution in two or more divided portions. [6] The method for reducing ozone according to any one of [2] to [5], wherein the ozone gas or the ozone-containing organic solvent is added to the solution of the polymer compound at a low temperature to a room temperature, and the mixture is stirred. [7] The method according to [6], wherein the stirring time is 1 hour or more after the addition of the ozone-containing organic solvent. [8] The method according to any one of [2] to [7], further comprising the step of adding nitrogen gas and stirring the ozone gas or the ozone-containing organic solvent to the solution of the polymer compound. [9] A step of reducing residual monomers in a solution of a polymer compound obtained by polymerizing a compound having a polymerizable unsaturated double bond by the method for reducing residual monomers according to any one of [1] to [8]; and a step of mixing a drug or a valuable substance with a solution of a polymer compound having a reduced amount of residual monomers to produce a transdermal absorption preparation; A method for producing a transdermal absorption preparation, comprising:

[10] The production method according to [9], wherein the polymer compound solution is a solution of 2-ethylhexyl acrylate-2-ethylhexyl methacrylate-dodecyl methacrylate copolymer.

[11] The method for producing the transdermal absorption preparation according to [9] or

[10] , wherein the solution of the polymer compound contains tulobuterol.

[12] A step of reducing residual monomers in a 2-ethylhexyl acrylate-2-ethylhexyl methacrylate-dodecyl methacrylate copolymer solution by the method for reducing residual monomers according to any one of [1] to [8]; and a step of producing a pressure-sensitive adhesive using a 2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate copolymer solution having a reduced amount of residual monomers; A method for producing a pressure-sensitive adhesive, comprising:

[13] A step of reducing residual monomers in a 2-ethylhexyl acrylate-acrylic acid copolymer solution or a 2-ethylhexyl acrylate-vinylpyrrolidone copolymer solution by the method for reducing residual monomers according to any one of [1] to [8]; and a step of producing a pressure-sensitive adhesive using a 2-ethylhexyl acrylate-acrylic acid copolymer solution or a 2-ethylhexyl acrylate-vinylpyrrolidone copolymer solution having a reduced amount of residual monomer; A method for producing a pressure-sensitive adhesive, comprising: [Effects of the Invention]

[0007] The present invention can make, for example, polymer compounds used on the human body or polymer compounds that come into contact with the human body during processing safer. According to the present invention, it is possible to efficiently reduce the amount of residual monomers in a polymer compound containing residual monomers. The method for reducing residual monomers in a polymer compound of the present invention has the effect of suppressing changes in molecular weight, viscosity, and stability of the polymer compound, which are caused by the residual monomers. In particular, the generation of monomer-related substances caused by the residual monomers is suppressed, leading to stabilization of the polymer compound. DETAILED DESCRIPTION OF THE INVENTION

[0008] Examples of the compound having a polymerizable unsaturated double bond include vinyl compounds such as styrene, vinyl chloride, vinyl acetate, and vinylpyrrolidone, and compounds having a carbon-carbon unsaturated double bond such as (meth)acrylic compounds such as (meth)acrylic acid, methyl (meth)acrylate, and octyl (meth)acrylate, but the present invention is not limited to these examples.

[0009] In this specification, "(meth)acrylic" means "acrylic" or "methacrylic".

[0010] Examples of polymeric compounds obtained by polymerizing a compound having a polymerizable unsaturated double bond include polymers obtained by polymerizing one or more of the above-mentioned compounds having a polymerizable unsaturated double bond.

[0011] The solution of the polymer compound may be, for example, a solution in which the polymer compound is dissolved in a solvent, or may be a reaction mixture obtained by polymerizing a compound having a polymerizable unsaturated double bond in a solvent by a method such as solution polymerization.

[0012] The type of solvent used for the solution of the polymer compound varies depending on the type of the polymer compound and cannot be determined in general. Therefore, it is usually preferable to select the solvent appropriately depending on the type of the polymer compound and the like.

[0013] In the present invention, it is preferable to use the reaction mixture before isolating the polymer compound as the solution of the polymer compound, since this does not require the troublesome operation of dissolving the polymer compound in a solvent.

[0014] The concentration of the polymer compound in the solution of the polymer compound is not particularly limited, but is generally 5 to 70% by mass, and preferably about 10 to 50% by mass.

[0015] There are no particular limitations on the method for introducing ozone into the polymer solution. Examples include a method in which ozone gas purified using a commercially available ozone generator is blown into the polymer solution using a bubbler. When this method is employed, the amount of ozone gas generated and blown in varies depending on the amount of polymer solution, but is preferably 1 to 100 mg / min. The amount of ozone added is preferably 20 to 1,000 mg / L, more preferably 50 to 500 mg / L, relative to the amount of the polymer compound solution. If the amount added is too high, the oxidizing effect of ozone may be strong, and other oxidized impurities may increase, while if the amount added is too low, the effect of reducing the residual monomer may be insufficient.

[0016] Another addition method involves prefilling an organic solvent with a high concentration of ozone gas, and then adding the ozone-containing organic solvent to the polymer solution while stirring. This allows for polymer treatment at a diluted ozone concentration. The number of times and intervals for adding the high-concentration ozone-containing organic solvent are preferably two or more additions, depending on the level of residual monomer reduction desired. The amount of ozone added per addition is preferably 5 to 50 mg per liter of polymer solution, and the addition interval is such that the next addition is made after the previously added ozone has disappeared or reached an extremely low concentration close to that. The addition interval is preferably 30 minutes or more, more preferably 1 hour or more. The upper limit of the addition interval is preferably 12 hours. The ozone-containing organic solvent may be ethyl acetate, acetone, or the like, and is not particularly limited as long as it is not a solvent that undergoes oxidation by ozone. The ozone content in the organic solvent is 20 to 1000 mg / L, preferably 100 to 500 mg / L.

[0017] The temperature of the polymer compound solution when ozone gas is introduced into the solution is not particularly limited, but from the viewpoint of efficiently detoxifying the polymer compound and ensuring safety during operation, it is desirable to set the temperature in the range of low temperature to room temperature, preferably -20 to 50°C, and more preferably 5 to 30°C.

[0018] It goes without saying that the time required to introduce ozone gas into the polymer compound solution cannot be determined in general terms, since it varies depending on the type of polymer compound, the amount of ozone gas introduced, the temperature of the solution, etc.

[0019] Thus, when ozone gas is introduced into the polymer solution, the unsaturated double bonds contained in the residual monomers contained in the polymer solution and in the polymer chains produced by the disproportionation reaction are cleaved by oxidative cleavage to form terminals containing hydroxyl groups or carboxyl groups.

[0020] For small-scale reactions, a glass vessel is used, while for large-scale reactions, a stainless steel reaction vessel with a glass surface is preferably used. The vessel is equipped with a stirring blade and a stirring motor to stir and mix the polymer compound solution evenly after it is poured into the vessel. It is desirable to have a temperature control device for the reaction vessel. An ozone inlet tube and a tube for venting the internal gas are also provided.

[0021] The polymer compound with reduced monomer content can be suitably used as a polymer compound used on the human body or a polymer compound that comes into contact with the human body during processing, etc. Examples of polymer compounds used on the human body or that come into contact with the human body during processing include cosmetics, pharmaceuticals, foods, packaging materials, paints, etc., but the present invention is not limited to these examples.

[0022] A solution of a polymer compound in which the amount of residual monomers has been reduced by the method for reducing residual monomers of the present invention can be suitably used to produce an adhesive or a transdermal absorption preparation, which is a pharmaceutical application of the adhesive. Examples of solutions of the polymer compounds that are raw materials for adhesives or transdermal absorption preparations include a solution of 2-ethylhexyl acrylate-2-ethylhexyl methacrylate-dodecyl methacrylate copolymer, a solution of 2-ethylhexyl acrylate-acrylic acid copolymer, and a solution of 2-ethylhexyl acrylate-vinylpyrrolidone copolymer. The adhesive layer that forms the adhesive or transdermal absorption preparation can be formed by applying a solution of the polymer compound onto a film (for example, release PET) and drying it. In the manufacturing process of a transdermal absorption preparation, a predetermined drug or valuable substance can be mixed into a solution of a polymer compound to produce a pharmaceutical product, a quasi-drug product, or a cosmetic product.

[0023] The drugs and valuable substances may be any substances that can permeate a biological membrane transdermally.

[0024] Examples of drugs include antipyretic, anti-inflammatory and analgesic agents, antiepileptic drugs, antipsychotic drugs, antidepressants and anti-anxiety drugs, anti-Parkinson's agents, antimanic drugs, anti-dementia drugs, hypnotics, sedatives, antispasmodics, muscle relaxants, autonomic nervous system acting agents, cerebral circulation and metabolism improving agents, cardiac stimulants, antianginal drugs, hypertensive and arrhythmia drugs, vasodilators, antihypertensive agents, hypertensive agents, diuretics, respiratory stimulants, antitussive and expectorant drugs, bronchodilators, drugs for treating asthma and nasal allergies, respiratory tract agents, cold drugs, antiemetics, antacids, and antiulcer drugs.

[0025] Examples of ingredients that can be incorporated as valuable substances in cosmetics include whitening ingredients, anti-wrinkle ingredients, anti-inflammatory ingredients, blood circulation promoting ingredients, antibacterial ingredients, anti-pruritic ingredients, various vitamins and their derivatives, antioxidant ingredients, anti-allergic ingredients, fragrances, etc. [Example]

[0026] The present invention will be described in more detail below with reference to the following examples. These examples are merely examples for specifically explaining the present invention, and the scope of the present invention is not limited to these examples. In this example, the room temperature was in the range of 20 to 25°C.

[0027] Example 1 50g of 2-ethylhexyl acrylate, 5g of acrylic acid, 145g of ethyl acetate, and 0.5g of azobisisobutyronitrile were placed in a 500cc separable flask reaction vessel, and the polymerization reaction was carried out for 24 hours while heating to 75°C and stirring the solution with a stirring blade. As a result, a copolymer of 2-ethylhexyl acrylate and acrylic acid was obtained in a yield of 98%.

[0028] After the polymerization reaction was completed, the residual monomers in the reaction mixture were quantitatively analyzed by gas chromatography using the internal standard method, and it was found that the reaction mixture contained 4,000 ppm of 2-ethylhexyl acrylate and 12,000 ppm of acrylic acid. This reaction mixture is referred to as Sample A.

[0029] Next, ozone was blown into the reaction mixture at room temperature with stirring for 30 minutes using an ozone generator (Jupeto, GL-3189A) at a flow rate of 10 mg / min. After the ozone blowing was completed, the mixture was stirred at 25°C for 12 hours. Nitrogen gas was then blown into the reaction mixture at room temperature for 6 hours to volatilize the remaining ozone. The residual monomers in the reaction mixture were quantitatively analyzed using a gas chromatograph with an internal standard method, and the remaining amounts of 2-ethylhexyl acrylate and acrylic acid were both found to be less than 50 ppm.

[0030] From the above results, it is clear that the introduction of ozone gas into a solution of a polymer compound obtained by polymerizing a compound having a polymerizable unsaturated double bond can efficiently remove residual monomers.

[0031] Example 2 200 cc of MAS811B adhesive solution (manufactured by Cosmedy Pharmaceutical Co., Ltd., residual monomer amount 2,000 ppm) was placed in a 500 cc separable flask reaction vessel, and the solution was stirred with a stirring blade while being treated for 3 hours at room temperature while generating ozone using the ozone generator of Example 1 under the same conditions as in Example 1. When the concentration of residual monomer in the adhesive solution after treatment was measured, it was found to be below the detection limit (50 ppm) of the gas chromatograph.

[0032] Example 3 50 cc of MAS811B adhesive solution (manufactured by Cosmedy Pharmaceutical Co., Ltd., residual monomer content 2,000 ppm) was placed in a 100 cc glass reaction vessel. Separately, ozone gas was blown into 50 cc of ethyl acetate at a flow rate of 10 mg / min using an ozone generator (Jupeto, GL-3189A) for 1 hour to obtain ozone-saturated ethyl acetate. 2 cc of the ozone-saturated ethyl acetate was added to the MAS811B adhesive solution, shaken well, and allowed to stand at room temperature for 4 hours for ozone treatment. The same treatment was then repeated twice. Tulobuterol was added to the adhesive solution before and after the ozone treatment, to obtain a medicinal tape having a thickness of 50 μm after drying and containing 4% by mass of tulobuterol. Tulobuterol and other low-molecular-weight compounds were extracted from this medicinal patch using ethanol, and peaks for tulobuterol and other low-molecular-weight compounds were confirmed in the chromatogram obtained by high-performance liquid chromatography. A similar chromatogram was measured and compared with that of MAS811B, which does not contain tulobuterol, and the peak derived from tulobuterol was identified. Although tulobuterol-derived analogues are produced in this medicinal patch, their production was suppressed by ozone treatment. See Table 1 below. In this table, RRT is the relative elution time, with the elution time of tulobuterol set to 1.

[0033] [Table 1]

[0034] Ozone treatment reduced the amount of residual monomers, which in turn reduced the amount of related substances.

Claims

1. A method for reducing residual monomers, comprising introducing ozone gas into a solution of a polymer compound obtained by polymerizing a compound having a polymerizable unsaturated double bond, wherein the ozone gas introduced is obtained by blowing the ozone gas into an organic solvent and adding the resulting ozone-containing organic solvent to the solution of the polymer compound.

2. 2. The method according to claim 1, wherein the ozone content in the organic solvent is 20 to 1,000 mg / L.

3. The method according to claim 1 or 2, wherein the ozone-containing organic solvent is added to the polymer compound solution in two or more divided portions.

4. The method according to any one of claims 1 to 3, wherein the ozone-containing organic solvent is added to the polymer compound solution at -20°C to 50°C and stirred.

5. The method according to claim 4, wherein the stirring time is 1 hour or more after the addition of the ozone-containing organic solvent.

6. The method according to any one of claims 1 to 5, further comprising the step of adding nitrogen gas and stirring the solution after adding the ozone-containing organic solvent to the solution of the polymer compound.

7. A step of reducing residual monomers in a solution of a polymer compound obtained by polymerizing a compound having a polymerizable unsaturated double bond by the method for reducing residual monomers according to any one of claims 1 to 6; a step of mixing a drug or a cosmetic ingredient with a solution of the polymer compound having a reduced amount of residual monomers to produce a transdermal absorption preparation; A method for producing a transdermal absorption preparation, comprising:

8. 8. The method according to claim 7, wherein the polymer compound solution is a solution of 2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate copolymer.

9. The method according to claim 7 or 8, wherein in the step of producing the transdermal absorption preparation, the solution of the polymer compound contains tulobuterol.

10. A step of reducing residual monomers in a 2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate copolymer solution by the method for reducing residual monomers according to any one of claims 1 to 6; a step of producing a pressure-sensitive adhesive using a 2-ethylhexyl acrylate / 2-ethylhexyl methacrylate / dodecyl methacrylate copolymer solution in which the residual monomer content has been reduced; A method for producing a pressure-sensitive adhesive, comprising:

11. A step of reducing residual monomers in a 2-ethylhexyl acrylate / acrylic acid copolymer solution or a 2-ethylhexyl acrylate / vinylpyrrolidone copolymer solution by the method for reducing residual monomers according to any one of claims 1 to 6; a step of producing a pressure-sensitive adhesive using a 2-ethylhexyl acrylate / acrylic acid copolymer solution or a 2-ethylhexyl acrylate / vinylpyrrolidone copolymer solution in which the residual monomer content has been reduced; A method for producing a pressure-sensitive adhesive, comprising:

Images