JP5970206B2 - Extraction method of chemicals - Google Patents

Description

  The present invention relates to a method for extracting a medicine. Specifically, the present invention relates to a method for extracting a chemical such as an anti-aging agent contained in a specimen composed of a polymer composition.

  For example, a rubber product such as a tire is formed using a rubber composition. This rubber composition contains various chemicals. From the viewpoint of grasping the performance of a product, it is extremely important to qualify the chemical contained in this product and to quantify the amount of this chemical. As a test method for qualitative or quantitative determination of this chemical, for example, “rubber compounding agent—test method—part 3: anti-aging agent” and JIS-K6229 defined in JIS-K6220-3. And “quantification of rubber-solvent extract”. Moreover, the examination example regarding the determination method of the free sulfur in rubber | gum is disclosed by Unexamined-Japanese-Patent No. 2003-302394.

JIS-K6220-3: 2001 “rubber compounding agent—test method—part 3: anti-aging agent” JIS-K6229: 1998 “Quantification of rubber-solvent extract”

JP 2003-302394 A

  When a chemical contained in a rubber specimen is qualitatively or quantitatively determined, the chemical is extracted from the specimen. In this extraction, a solvent is brought into contact with the specimen. Thereby, the chemical | medical agent contained in this test substance diffuses in rubber | gum, and transfers to a solvent.

  In the above extraction, the rubber is present in the solvent while maintaining its form or in a swollen state. In this extraction, the rubber morphology is kept static. The time required for extraction mainly depends on the diffusion of the drug. For this reason, there is a problem that this extraction takes time.

  In the above extraction, the solvent penetrates into the rubber. When this solvent stays in the rubber, there is a problem that it becomes difficult to extract the whole amount of the chemical. In this case, there is a possibility that the quantitative accuracy of the chemical is impaired.

  An object of the present invention is to provide a method for extracting a chemical contained in a specimen composed of a polymer composition in a short time.

The method for extracting a drug according to the present invention includes:
(1) a step of preparing a specimen containing a polymer and a medicine;
(2) adding a first solvent to swell or dissolve the polymer,
(3) A step of adding a second solvent to shrink or precipitate the polymer, and (4) a step of evaporating the second solvent.

  Preferably, in this chemical extraction method, the number of treatments by the flow including the step of adding the first solvent, the step of adding the second solvent, and the step of evaporating the second solvent is 1 to 4 times. is there.

  Preferably, in this chemical extraction method, the solubility parameter of the first solvent is 7.0 or more and 9.5 or less.

  Preferably, in this chemical extraction method, the solubility parameter of the second solvent is from 10.0 to 16.0.

  Preferably, in this chemical extraction method, the chemicals are antioxidants, vulcanization accelerators, processing aids, antioxidants, light stabilizers, plasticizers, softeners, vulcanization accelerators and coupling agents. Is at least one selected from the group consisting of

  The chemical analysis method according to the present invention includes a step of extracting a chemical contained in a specimen using any one of the extraction methods described above.

  In the extraction method according to the present invention, the polymer is swollen or dissolved by adding the first solvent. Thereafter, the polymer is contracted or precipitated by the addition of the second solvent. In this extraction method, the morphology of the polymer is changed. This morphological change facilitates the discharge of chemicals in the polymer out of the polymer. According to this extraction method, the medicine can be extracted in a short time. In addition, since almost all of the chemical contained in the specimen is extracted, this extraction method can contribute to the improvement of the chemical analysis accuracy.

FIG. 1 is a flowchart illustrating a chemical analysis method according to an embodiment of the present invention.

  Hereinafter, the present invention will be described in detail based on preferred embodiments with appropriate reference to the drawings.

  The analysis method shown in the flowchart of FIG. 1 is for quantifying a chemical contained in a specimen composed of a polymer composition. This analysis method includes a preparation process (STEP 1), a first charging process (STEP 2), a second charging process (STEP 3), an evaporation process (STEP 4), and an analyzing process (STEP 5).

  In the preparation step (STEP 1), a specimen is prepared. As mentioned above, this specimen consists of a polymer composition. The specimen includes a polymer and a drug. Examples of this polymer include resins and rubbers. Examples of the resin include polyurethane, polyester, polyamide, polyethylene, polypropylene, polystyrene, polyvinyl chloride, ethylene-vinyl acetate copolymer, silicone, and various thermoplastic elastomers. Rubbers include natural rubber, polybutadiene, styrene-butadiene copolymer, polyisoprene, ethylene-propylene-diene terpolymer, polychloroprene, acrylonitrile-butadiene copolymer, isobutylene-isoprene copolymer, butyl rubber and halogen. Illustrated is butyl rubber.

  As a chemical | medical agent, if it mix | blends with a polymer, it will not restrict | limit in particular. For example, examples of the chemical include an antioxidant, a vulcanization accelerator, a processing aid, an antioxidant, a light stabilizer, a plasticizer, a softening agent, a vulcanization acceleration aid, and a coupling agent.

  The anti-aging agent is not particularly limited as long as it is blended with the polymer. For example, as this antioxidant, naphthylamine type such as phenyl-α-naphthylamine, octylated diphenylamine, diphenylamine type such as 4,4′-bis (α, α′-dimethylbenzyl) diphenylamine, N-isopropyl-N ′ P-phenylenediamine such as -phenyl-p-phenylenediamine, N- (1,3-dimethylbutyl) -N'-phenyl-p-phenylenediamine, N, N'-di-2-naphthyl-p-phenylenediamine Amine-based anti-aging agent such as quinoline; quinoline-based anti-aging agent such as polymer of 2,2,4-trimethyl-1,2-dihydroquinoline; 2,6-di-t-butyl-4-methylphenol, styrene Monophenols such as fluorinated phenols, tetrakis- [methylene-3- (3 ′, 5′-di-t-butyl-4′-hydroxyphene Nyl) propionate] bis such as methane, tris, phenolic antioxidant such as polyphenol and polyphenol antioxidant such as WINGSTAY-L.

  The vulcanization accelerator is not particularly limited as long as it is blended with the polymer. For example, as the crosslinking accelerator, N-cyclohexyl-2-benzothiazylsulfenamide, Nt-butyl-2-benzothiazolesulfenamide, N-oxyethylene-2-benzothiazolesulfenamide, N -Sulfenamide-based crosslinking accelerators such as oxyethylene-2-benzothiazole sulfenamide, N, N'-diisopropyl-2-benzothiazole sulfenamide; diphenylguanidine, diortolylguanidine, orthotolylbiguanidine, etc. Guanidine-based crosslinking accelerators; Thiourea-based crosslinking accelerators such as diethylthiourea; Thiazole-based crosslinking accelerators such as 2-mercaptobenzothiazole, di-2-benzothiazolyl disulfide and 2-mercaptobenzothiazole zinc salt; Tetramethylthiuram Monosulfide Thiuram-based crosslinking accelerators such as tetramethylthiuram disulfide; Dithiocarbamate-based crosslinking accelerators such as sodium dimethyldithiocarbamate and zinc diethyldithiocarbamate, and xanthogenic acid-based crosslinking such as sodium isopropylxanthate, zinc isopropylxanthate, and zinc butylxanthate Accelerators are mentioned.

  The processing aid is not particularly limited as long as it is blended with the polymer. Examples of the processing aid include fatty acids, fatty acid esters, fatty acid amides, fatty acid metal salts and the like.

  The antioxidant is not particularly limited as long as it is blended with the polymer. For example, the antioxidant includes phenol-based antioxidants such as 2,6-di-t-butyl-4-methylphenol; phosphite-based antioxidants such as tris (nonylphenyl) phosphite and And sulfur-based antioxidants such as lauryl thiodipropionate.

  The light stabilizer is not particularly limited as long as it is blended with the polymer. For example, examples of the light stabilizer include salicylic acid derivatives such as phenyl salicylate; benzophenone light stabilizers such as 2,4-dihydroxybenzophenone and bis (2,2,6,6-tetramethyl-4-piperidyl) sebacate. Examples include hindered amine light stabilizers.

  The plasticizer is not particularly limited as long as it is blended with the polymer. Examples of the plasticizer include phthalic acid derivatives such as dimethyl phthalate, diethyl phthalate, di- (2-ethylhexyl) phthalate, di-n-octyl phthalate, diisooctyl phthalate, di-n-alkyl phthalate, and dimethyl isophthalate; Tetrahydrophthalic acid derivatives such as di- (2-ethylhexyl) tetrahydrophthalate; adipic acid derivatives such as dibutyl adipate, dimethyl adipate, di- (2-ethylhexyl) adipate, diisodecyl adipate; azelaic acid derivatives; sebacic acid derivatives; 2-acid derivative; maleic acid derivative; fumaric acid derivative; trimellitic acid derivative; pyromellitic acid derivative; citric acid derivative; itaconic acid derivative; oleic acid derivative; ricinoleic acid derivative; Other fatty acid derivatives; sulfonic acid derivatives; phosphoric acid derivative; glutaric acid derivatives; other mono-ester plasticizer; glycol derivatives; glycerol derivatives; paraffin derivatives, epoxy derivatives and polyester, polymerizable plasticizers such polyethers.

  The softening agent is not particularly limited as long as it is blended with the polymer. Examples of the softener include petroleum-based softeners such as paraffinic process oil and naphthenic process oil, special process oils, mineral oil-based softeners such as ethylene and α-olefin co-oligomers, paraffin wax, and liquid paraffin. Examples include vegetable oil-based softeners such as castor oil, cottonseed oil and linseed oil.

  The vulcanization acceleration aid is not particularly limited as long as it is blended with the polymer. For example, examples of the vulcanization acceleration aid include fatty acids such as stearic acid and oleic acid and derivatives thereof, and amines such as di-n-butylamine and dicyclohexylamine.

  The coupling agent is not particularly limited as long as it is blended with the polymer. For example, the coupling agent includes silanes such as γ-chloropropyltrimethoxysilane and vinyltrichlorosilane, aluminums such as acetoalkoxyaluminum diisopropylate, and isopropyltriisostearoyl titanate, isopropyltris (dioctylpyrophosphate). A titanate system such as titanate can be mentioned.

  In this preparation step (STEP 1), the specimen is sampled from the product. A molded article formed using a composition equivalent to the composition constituting the product may be used as this specimen. Examples of this product include tires, shoes, and hoses. For example, when this specimen is sampled from a tire, a part of the tire, such as a tread, a sidewall, and a clinch, is cut out as a specimen. This specimen is preferably finely pulverized.

  In this analysis method, when a specimen is prepared, a first solvent is introduced (STEP 2). Thereby, the first solvent is brought into contact with the specimen. In the first charging step (STEP 2), the specimen may be charged into a container filled with the first solvent by charging the first solvent. The first solvent may be charged into the container in which the sample is charged.

  In the first charging step (STEP 2), the first solvent penetrates into the specimen. The polymer that forms part of the specimen comes into contact with the first solvent. This contact state is maintained for a predetermined time. In the present application, this time is referred to as a first holding time T1.

  In the first charging step (STEP 2), when the first solvent comes into contact with the polymer, the polymer swells or dissolves in the first solvent. The chemical contained in this sample is eluted in the first solvent.

  In the first charging step (STEP 2), the volume V1 of the first solvent to be charged is preferably at least three times the volume Vs of the specimen from the viewpoint of polymer swelling or dissolution. From the viewpoint of the quantitative accuracy of chemicals and the prevention of excessive use of solvents, the volume V1 of the first solvent is preferably 50 times or less the volume Vs of the specimen.

  In the first charging step (STEP 2), an organic solvent having a low polarity is preferably used as the first solvent. More specifically, the solubility parameter of the first solvent is preferably 7.0 or more and 9.5 or less. This promotes swelling or dissolution of the polymer in the specimen in contact with the first solvent. Solvents having a solubility parameter of 7.0 or more and 9.5 or less include aromatic organic solvents such as benzene (9.2) and toluene (8.8); hexane (7.3), heptane (7. 7), aliphatic organic solvents such as cyclohexane (8.2); halogenated organic solvents such as chloroform (9.3), chlorobenzene (9.5), dichlorobenzene (10.0); ethyl acetate (9.1) ), Ester organic solvents such as ethyl propionate (8.4), and ether organic solvents such as tetrahydrofuran (9.1). In addition, the numerical value described in parentheses represents a solubility parameter. This solubility parameter is represented by the square root of the cohesive energy density in the liquid, and is used as an index characterizing the solubility. In the present application, values obtained based on the Small molecular binding constants in Table 13-2 on page 287 of “Paint Flow and Pigment Dispersion” (supervised by Kenji Ueki, published by Kyoritsu Shuppan Co., Ltd.) are expressed as solubility parameters. Has been. The same applies to the solubility parameter of the second solvent, which will be described later.

  In this analysis method, after the first solvent is charged, the second solvent is charged (STEP 3). In the second charging step (STEP 3), the second solvent may be charged into the container containing the sample and the first solvent. The mixture containing the specimen and the first solvent may be charged into another container filled with the second solvent by charging the second solvent. From the viewpoint of quantitative accuracy, it is more preferable that the second solvent is put into a container containing the specimen and the first solvent.

  In the second charging step (STEP 3), the second solvent comes into contact with the polymer by charging the second solvent. Thereby, the swollen polymer contracts or precipitates.

  In the second charging step (STEP 3), the volume V2 of the second solvent to be charged is preferably at least twice the volume V1 of the first solvent from the viewpoint of polymer shrinkage or precipitation. From the viewpoint of the accuracy of quantitative determination of chemicals and the prevention of excessive use of solvents, the volume V2 of the second solvent is preferably 20 times or less the volume V1 of the first solvent.

  In the second charging step (STEP 3), an organic solvent having a high polarity is preferably used as the second solvent. More specifically, the solubility parameter of the second solvent is preferably 10.0 or more and 16.0 or less. This promotes shrinkage or precipitation of the polymer in contact with the second solvent. Examples of the solvent having a solubility parameter of 10.0 or more and 16.0 or less include acetone (10.0), acetonitrile (11.9), methanol (14.5), and ethanol (12.7).

  In this analysis method, since the chemical is extracted by the first input step (STEP 2) and the second input step (STEP 3), the specimen is altered. In this analysis method, after the second solvent is charged, the altered specimen is taken out from the container. This altered specimen contains a polymer. In this analysis method, after the second solvent is added, the contracted or precipitated polymer is removed from the container.

  In this analysis method, when the contracted or precipitated polymer is taken out, the evaporation step (STEP 4) is started. In this evaporation step (STEP 4), the first solvent or the second solvent evaporates and the extracted chemical is concentrated. Thereby, the residue containing the chemical | medical agent contained in a test substance is obtained. In the present application, the flow including the first charging process (STEP 2), the second charging process (STEP 3), and the evaporation process (STEP 4) is referred to as an extraction process. In other words, the analysis method of the present invention includes a step of extracting a chemical contained in a specimen using an extraction method including a first input step (STEP 2), a second input step (STEP 3), and an evaporation step (STEP 4). It is out.

  In this analysis method, the residue obtained in the evaporation step (STEP 4) is diluted with a solvent. This provides a sample for analysis. Analysis is performed on this sample (STEP 5).

  In this analysis method, an organic solvent having a low polarity is preferable as a solvent used for dilution from the viewpoint of promoting dissolution of chemicals. Examples of such solvents include aromatic organic solvents such as benzene and toluene, aliphatic organic solvents such as hexane, heptane, and cyclohexane, halogenated organic solvents such as chloroform, methylene chloride, chlorobenzene, and dichlorobenzene, ethyl acetate, and propionic acid. Examples thereof include ester organic solvents such as ethyl and ether organic solvents such as tetrahydrofuran. In this analysis method, the same solvent as the above-mentioned first solvent may be used as a solvent for this dilution.

  The specimen contains a large number of drugs. For this reason, from the viewpoint that these chemicals can be separated and analyzed for each, in this analysis step (STEP 5), the chemicals are analyzed by chromatography. Examples of this chromatography include liquid chromatography, gas chromatography, thin layer chromatography, and gel permeation chromatography. From the viewpoint of analysis time and easy handling, liquid chromatography is preferred as this chromatography.

  An instrument used for liquid chromatography (referred to as a liquid chromatograph) includes a detector, a column, and an eluent as main components for obtaining a chromatogram. A commonly used detector is used as this detector. Examples of the detector include an absorbance detector, an optical rotation detector, a refractive index detector, and a mass spectrum detector. From the viewpoint of being excellent in the sensitivity of trace components, an absorbance detector and a mass spectrum detector are preferable as this detector. As the column packing, silica gel can be used in the normal phase system. In the reverse phase system, silica gel whose surface is modified with an octadecylsilyl group (also referred to as (C18 silica gel)) can be used. From the viewpoint of easily obtaining a high number of theoretical plates and high resolution, the filler is preferably silica gel whose surface is modified with a reverse-phase octadecylsilyl group. Examples of the normal phase eluent include solvents with low polarity such as hexane and ether. Examples of the reverse phase eluent include methanol, a mixed solution of methanol and water, acetonitrile, and a mixed solution of acetonitrile and water.

  In this analysis step (STEP 5), a chromatogram including a chemical peak is obtained by analysis using a chromatograph. In chromatography, the concentration of a drug is quantified based on the peak area of the drug.

  In this analysis method, as described above, in the first charging step (STEP 2), the chemical contained in the specimen is eluted into the first solvent. In the second charging step (STEP 3), the polymer swollen or dissolved in the first charging step (STEP 1) is contracted or precipitated. In this analytical method, the polymer morphology is changed. In other words, the polymer is dynamically transformed. This morphological change facilitates the expulsion of the drug in the polymer that forms part of the specimen out of the polymer. In this analytical method involving transformation of the polymer, the chemicals in the polymer are extracted in a short time. Moreover, almost all of the chemical contained in the specimen is extracted. In the extraction step in this analysis method, the drug is extracted at a high recovery rate, and the time required for extracting the entire amount is extremely short. This extraction process can contribute to improvement of analysis accuracy and reduction of analysis time.

  In this analysis method, from the viewpoint of improving analysis accuracy, the process of the extraction process may be repeatedly performed before the analysis process (STEP 5). Thereby, further improvement in analysis accuracy is achieved. From this point of view, the number of treatments in this extraction step is preferably 1 or more, more preferably 2 or more. From the viewpoint that the influence on the analysis time can be suppressed, the number of processing is preferably 4 times or less. When the process is repeated in the extraction step, the specimen taken out before the evaporation step (STEP 4) is again input into the container in the first input step (STEP 2).

  Hereinafter, the effects of the present invention will be clarified by examples. However, the present invention should not be construed in a limited manner based on the description of the examples.

[Example 1]
From 100 parts by weight of natural rubber (TSR20; hereinafter referred to as NR) mixed with 1 part by weight of an anti-aging agent (trade name “BHT” manufactured by Ouchi Shinsei Chemical Industry Co., Ltd .; hereinafter referred to as medicine A) using a roll, A specimen (mass = 1 g) was prepared. 30 ml of the first solvent was added to swell the NR. Tetrahydrofuran (hereinafter referred to as THF) was used as the first solvent. The solubility parameter of this THF is 9.1. 90 ml of the second solvent was added to precipitate NR. Methanol (hereinafter referred to as MeOH) was used as the second solvent. The solubility parameter of this MeOH is 14.5. Heated to evaporate THF and MeOH. The residue thus obtained was made into a 10 ml solution with THF, and this solution was used as a sample for analysis. In Example 1, the extraction process was performed once. The extraction time was 4 hours.

About the said sample, the chemical | medical agent A in a test substance was quantified on the conditions shown below using the liquid chromatograph (The brand name "CBM-20A" by Shimadzu Corporation Corp.).
Flow rate = 1 ml / min
Column oven temperature = 40 ° C
Detector = Absorbance detector (Measures absorbance at 280 nm)
Eluent = mixture of MeOH and water (MeOH / water = 9/1)

[Example 2-4]
The amount of chemical A was determined in the same manner as in Example 1 except that the number of treatments in the extraction step was as shown in Table 1 below. In Example 2, the extraction time was 8 hours. In Example 3, the extraction time was 12 hours. In Example 4, the extraction time was 16 hours.

[Example 5]
Styrene-butadiene copolymer (trade name “Nippol SBR1502” manufactured by Nippon Zeon Co., Ltd .; hereinafter referred to as SBR) to 100 parts by mass of an anti-aging agent (trade name “NOCRACK 6C” manufactured by Ouchi Shinsei Chemical Co., Ltd.); Drug B) A sample (mass = 1 g) was prepared from a mixture of 1 part by mass using a roll, and the number of treatments in the extraction process was changed to 2 times. Quantification was performed. In Example 5, the extraction time was 8 hours.

[Example 6]
Polybutadiene (trade name “BR150B” manufactured by Ube Industries, Ltd .; hereinafter referred to as “BR”) and 100 parts by mass of a vulcanization accelerator (trade name “Noxeller NS” manufactured by Ouchi Shinsei Chemical Co., Ltd .; hereinafter referred to as “C”) 1 mass A sample (mass = 1 g) was prepared from what was mixed using a roll, and the amount of chemical C was quantified in the same manner as in Example 1 except that the number of treatments in the extraction process was set to two. In Example 6, the extraction time was 8 hours.

[Example 7]
A sample (mass = 1 g) was prepared from 100 parts by mass of NR mixed with 1 part by mass of drug C1 using a roll, and the drug was processed in the same manner as in Example 1 except that the number of treatments in the extraction process was set to 2 times. B was quantified. In Example 7, the extraction time was 8 hours.

[Comparative Example 1]
The amount of drug A was determined in the same manner as in Example 1 except that drug A was extracted from the specimen used in Example 1 by Soxhlet extraction with MeOH. In Comparative Example 1, the extraction time was 24 hours.

[Comparative Example 2]
The amount of chemical A was determined in the same manner as in Comparative Example 1 except that the extraction time was 48 hours.

[Comparative Example 3]
A sample (mass = 1 g) was prepared from 100 parts by mass of SBR mixed with 1 part by mass of drug A using a roll, and drug A was extracted from this sample by Soxhlet extraction with MeOH in the same manner as in Example 1. Then, the chemical A was quantified. In Comparative Example 3, the extraction time was 24 hours.

[Comparative Example 4]
The sample used in Example 1 was immersed in a solution in which MeOH and chloroform were mixed at a volume ratio of 1: 1, and left at room temperature (about 25 ° C.) for 24 hours to extract drug A from this sample. In the same manner as in Example 1, the chemical A was quantified. The solubility parameter of this chloroform is 9.3.

[Efficacy evaluation]
From the quantification result, the mass M of the chemical contained in 100 g of the sample was estimated. Values obtained by multiplying the mass M by 100 are shown in Tables 1 to 3 below as drug recovery rates by extraction. The closer this value is to 100, the better.

  As shown in Tables 1 to 3, the analysis method of the example has a higher evaluation than the analysis method of the comparative example. From this evaluation result, the superiority of the present invention is clear.

  The method described above can be applied to various analyses.

Claims (4)

Preparing a specimen containing a polymer and a drug;
Adding the sample and the first solvent to a container to swell or dissolve the polymer; and
Adding a second solvent to the container in which the specimen and the first solvent are charged, and shrinking or precipitating the swollen or dissolved polymer; and
And a step of evaporating said second solvent and Nde including,
The solubility parameter of the first solvent is 7.0 or more and 9.5 or less,
The chemical | medical agent extraction method whose solubility parameter of said 2nd solvent is 10.0-16.0 .   The chemical | medical agent of Claim 1 whose process frequency by the flow including the process of supplying the said 1st solvent, the process of supplying the said 2nd solvent, and the process of evaporating this 2nd solvent is 1 to 4 times. Extraction method. The chemical is at least one selected from the group consisting of an antioxidant, a vulcanization accelerator, a processing aid, an antioxidant, a light stabilizer, a plasticizer, a softening agent, a vulcanization acceleration aid, and a coupling agent. The method for extracting a medicine according to claim 1 or 2 . A method for analyzing a medicine, comprising the step of extracting a medicine contained in a specimen using the extraction method according to any one of claims 1 to 3 .

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