WO2016133124A1 - Method for inhibiting penetration of insect pest repellant into skin and agent for inhibiting penetration of insect pest repellant into skin - Google Patents

Method for inhibiting penetration of insect pest repellant into skin and agent for inhibiting penetration of insect pest repellant into skin Download PDF

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Publication number
WO2016133124A1
WO2016133124A1 PCT/JP2016/054582 JP2016054582W WO2016133124A1 WO 2016133124 A1 WO2016133124 A1 WO 2016133124A1 JP 2016054582 W JP2016054582 W JP 2016054582W WO 2016133124 A1 WO2016133124 A1 WO 2016133124A1
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Prior art keywords
skin
pest repellent
polyalkylene glycol
penetration
pest
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PCT/JP2016/054582
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French (fr)
Japanese (ja)
Inventor
鋭三郎 阿南
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アース製薬株式会社
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Priority to CN201680010760.8A priority Critical patent/CN107249322B/en
Priority to JP2017500714A priority patent/JP6708623B2/en
Publication of WO2016133124A1 publication Critical patent/WO2016133124A1/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
    • A01N25/10—Macromolecular compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/06—Oxygen or sulfur directly attached to a cycloaliphatic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group —CO—N<, e.g. carboxylic acid amides or imides; Thio analogues thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N51/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds having the sequences of atoms O—N—S, X—O—S, N—N—S, O—N—N or O-halogen, regardless of the number of bonds each atom has and with no atom of these sequences forming part of a heterocyclic ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/39—Derivatives containing from 2 to 10 oxyalkylene groups
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/86—Polyethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/02—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings containing insect repellants

Definitions

  • the present invention relates to a method for suppressing penetration of a pest repellent into the skin and a penetration inhibitor for penetration of the pest repellent into the skin.
  • various pest repellents have been used to prevent damage from blood-sucking insects such as mosquitoes, abs and bed bugs.
  • various examinations are made in order to improve the feeling of use, reduce irritation, and increase the sustainability of the repellent effect.
  • Patent Document 1 discloses a pest repellent composition in which specific silicic acid particles are blended in order to maintain the repellent effect of the pest repellent component.
  • Patent Document 2 discloses a pest repellent composition containing an ultraviolet absorber for suppressing decomposition by light, and a human pest repellent which is combined with natural mineral water to suppress irritation of diet, which is a pest repellent component. Is disclosed.
  • Patent Document 2 the pest repellent for human body of Patent Document 2 is not practical because it is not easy to obtain natural mineral water to be blended and it is difficult to supply stably.
  • an object of the present invention is to provide a method for suppressing penetration of a pest repellent into the skin in order to improve the sustainability of the pest repellent effect on the skin over a long period of time with less irritation by the drug.
  • the present inventor applied polyalkylene glycol to the skin together with a pest repellent to suppress penetration of the pest repellent into the skin, and the pest repellent was applied to the epidermis (skin surface) for a long time.
  • the present invention has been completed.
  • the present invention is as follows. 1. A method of suppressing penetration of a pest repellent into the skin by applying polyalkylene glycol to the skin together with the pest repellent. 2. 2. The method according to 1 above, wherein the pest repellent has a log P value of 1 or more. 3. 3. The method according to 1 or 2 above, wherein the polyalkylene glycol has a molecular weight of 200 to 20000. 4). 4. The method according to any one of 1 to 3, wherein the polyalkylene glycol is polypropylene glycol. 5. A pest repellent penetration inhibitor for skin containing polyalkylene glycol. 6). Use of polyalkylene glycol to suppress penetration of a pest repellent applied on the skin into the skin.
  • the penetration of the pest repellent into the skin can be suppressed by applying the polyalkylene glycol together.
  • the pest repellent can be retained on the skin for a long time, and the sustainability of the pest repellent effect on the skin can be improved.
  • the pest repellent effect can be maintained for a long time, and a preparation with less irritation to the human body can be provided.
  • the pest repellent is used at a high concentration, the penetration of the pest repellent into the skin can be suppressed, so that the irritation to the skin of the pest repellent can be suppressed, and more to the human body.
  • a highly safe formulation can be provided.
  • FIG. 1 is a schematic diagram of a horizontal diffusion cell used in a skin absorption inhibition test.
  • the present invention provides a method for suppressing penetration of a pest repellent into the skin by applying polyalkylene glycol to the skin together with the pest repellent.
  • the present invention also provides a method for using polyalkylene glycol to suppress penetration of a pest repellent applied on the skin into the skin.
  • various synthetic or natural compounds having a repellent action or blood sucking inhibitory action against biting pests can be used.
  • N, N-diethyl-m-toluamide hereinafter also referred to as diet
  • p-menthane-3,8-diol 3- (N-acetyl-n-butyl) aminopropionic acid ethyl ester
  • n-hexyltriethylene glycol monoether methyl 6-n-pentyl-cyclohexene-1-carboxylate
  • dimethyl phthalate eucalyptol
  • menthol menthyl acetate
  • Citronella peppermint, cedarwood, lavender, tea tree oil, cinnamon bark, camphor, lemongrass, clover, ginger, geranium, bergamont, laurel, pine, red peach, Benny royal, eucalyptus, Indian sedan, etc.
  • Extracted essential oils and extracts, as well as pyrethroids such as pyrethrin, allethrin, phthalthrin, resmethrin, flamethrin, phenothrin, permethrin, ciphenothrin, praretrin, etofenprox, empentrin, transfluthrin, methfluthrin, profluthrin, etc. be able to.
  • pest repellents can be used singly or in combination of two or more, and among these, diet is preferred from the viewpoint of high versatility.
  • the pest repellent of the present invention preferably has a log P value of 1 or more.
  • the log P value is a coefficient representing polarity depending on the ease of distribution of a substance between water and octanol, which is defined in Chemical Reviews vol 71 (6), 525 (1971).
  • the log P value of the drug can be calculated by calculation software (PALAAS: manufactured by CompDrug Chemistry Ltd.).
  • a pest repellent having a log P value of 1 or more has good affinity with a hydrophobic stratum corneum, and therefore has good wettability on the stratum corneum surface. Therefore, the penetration area into the skin increases. Since the penetration into the skin is proportional to the penetration area between the pest repellent and the skin, the larger the penetration area, the greater the penetration amount.
  • the effect of the present invention that suppresses the penetration of the pest repellent into the skin by the polyalkylene glycol described later is more prominent as the pest repellent has a log P value of 1 or more and the amount of penetration into the skin. Therefore, it is preferable.
  • polyalkylene glycol is applied to the skin together with the pest repellent.
  • polyalkylene glycol is applied to the skin together with a pest repellent.
  • the present invention also includes a method of suppressing the penetration of the pest repellent into the skin by applying polyalkylene glycol to the skin together with the pest repellent and improving the persistence of the pest repellent effect of the pest repellent on the skin. It is to provide.
  • the present invention also provides a method for suppressing the penetration of a pest repellent into the skin and applying the pest repellent to the skin by applying the polyalkylene glycol to the skin together with the pest repellent.
  • the molecular weight of the polyalkylene glycol is preferably 200 to 20000, more preferably 200 to 5000. When the molecular weight of the polyalkylene glycol is 200 or more, it is preferable because the effect is remarkable.
  • the degree of polymerization of the polyalkylene glycol is preferably 3 or more, more preferably 4 to 400.
  • the degree of polymerization of the polyalkylene glycol is 3 or more, the effect of the present invention is sufficiently obtained, and when it is 4 or more, the effect becomes more remarkable.
  • a polyalkylene glycol having a polymerization degree of 400 or less is preferable because of its high versatility.
  • the polyalkylene glycol preferably has 2 to 4 carbon atoms, more preferably 2 to 3 carbon atoms.
  • the carbon number of the polyalkylene glycol is 2 or more, the effect of the present invention is remarkable, and when it is 4 or less, it is preferable because the compatibility with various components is high when the pest repellent composition is used.
  • the polyalkylene glycol may be linear or branched. Specific examples include polypropylene glycol and polyethylene glycol. From the viewpoints of versatility, stability and mildness to skin, polypropylene glycol and polyethylene glycol are preferable, and polypropylene glycol is particularly preferable. Various polyalkylene glycols may be used alone or in combination of two or more.
  • suitable polyalkylene glycol in the present invention examples include polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 800, polyethylene glycol 1000, polypropylene glycol 1000, polypropylene glycol 2000, and polypropylene glycol 4000.
  • the applied amount of the polyalkylene glycol when the applied amount of the pest repellent is 1 is preferably 0.025 or more by mass ratio, 0.05 More preferably. It is because the effect which suppresses the penetration
  • both the pest repellent and the polyalkylene glycol may be applied simultaneously, or may be applied separately. From the viewpoint of easy spreading on the entire skin, the stimulation of pest repellents such as diet, etc. being alleviated, and from the viewpoint of simplicity, it is preferable to apply both to the skin at the same time.
  • the above-mentioned pest repellent and polyalkylene glycol When applying the above-mentioned pest repellent and polyalkylene glycol to the skin, it can be applied to the skin as various preparations such as a pump agent, a lotion agent, a wet tissue agent, a roll-on agent, a coating agent, an aerosol agent, and the like.
  • the preparation is prepared using a known carrier, propellant, solvent, emulsifying / dispersing agent, etc., and if necessary, a nonwoven fabric, an actuator, an applicator, What is necessary is just to make it a desired formulation form combining with a pump apparatus, an aerosol apparatus, etc.
  • the amount of the diet attached to the skin is 1.5 mg / 100 cm 2 or more, and the polyalkylene glycol skin It is preferable to apply so that the amount of adhesion to the surface becomes 0.3 mg / 100 cm 2 or more.
  • a deposit of 1.5 to 150 mg / 100 cm 2 for diet and 0.3 to 50 mg / 100 cm 2 for polyalkylene glycol it is more preferable to use a deposit of 1.5 to 150 mg / 100 cm 2 for diet and 0.3 to 50 mg / 100 cm 2 for polyalkylene glycol.
  • a coating agent, a roll-on agent or a wet tissue agent for example, when an aerosol agent or a pump agent is used when applied to the skin, a nozzle, a valve, an injection pressure, etc. are adjusted, a coating agent, a roll-on agent or a wet tissue agent.
  • the adhesion amount of the pest repellent and the polyalkylene glycol to the skin may be adjusted by adjusting the shape of the coated surface or the material property of the coated part.
  • the aerosol container may be pressurized and filled so that the propellant is 5 to 95 v / v% with respect to the whole preparation.
  • the propellant for example, liquefied petroleum gas, dimethyl ether, alternative chlorofluorocarbon, compressed gas (oxygen, nitrogen), and a mixture thereof can be used.
  • the basis weight of the support is preferably 20 to 80 g / m 2 .
  • the desired pest repellent and polyalkylene glycol can be taken in, retained, applied and impregnated.
  • the pest repellent at 70 to 300 ml / m 2 on a support having a thickness of about 0.1 to 5 mm.
  • woven fabric such as flannel, cotton, silk, polyester, nylon, or the like made from these materials
  • non-woven fabric such as polyester, polyolefin, nylon, cotton, rayon, vinylon, cellulose, or the like made from these materials
  • a sheet-like resin foam obtained by foaming polyethylene, polypropylene, ethylene-vinyl acetate copolymer, polyvinyl chloride, or the like can be used.
  • Examples of the carrier include water such as tap water, purified water, ionic water, ethyl alcohol, isopropyl alcohol, lauryl alcohol, cetanol, 2-hexyldecanol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, lanolin alcohol, and other lower alcohols,
  • Examples thereof include polyhydric alcohols such as ethylene glycol, diethylene glycol monoethyl ether, triethylene glycol, propylene glycol, 1,3-butylene glycol and glycerin, and hydrocarbon solvents.
  • Examples of the emulsifying / dispersing agent include sorbitan trioleate, polyoxyethylene monooleate, polyoxyethylene alkyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, decaglycerin monooleate,
  • Examples include surfactants such as propylene glycol dioleate, polyoxyethylene stearamide, polyoxyethylene lauryl ether phosphate, glycerin fatty acid ester, stearyl alcohol, polyvinyl pyrrolidone, and lanolin fatty acid, lower alcohols, and polyhydric alcohols.
  • enhancing the repellent effect of pests for example, any amount of powder, fragrance component, bactericidal / preservative component, moisturizing component, thickener, etc. It can also be applied to the skin.
  • silica compounds such as hydrophobic silica, calcium silicate, diatomaceous earth, high-purity silica, and anhydrous silicic acid
  • inorganic powders such as talc, calcium carbonate, magnesium stearate, acid clay, white carbon, pearlite
  • octenyl succinic acid Metal salt of alkenyl succinate starch such as corn starch ester aluminum
  • Natural powder such as silk powder
  • Powder such as resin such as nylon and polypropylene
  • Fragrance ingredients such as menthol, mint oil, mint oil; Phenol, paraoxybenzoic acid ester
  • Bactericidal and antiseptic components such as salicylic acid and its salts, benzalkonium chloride, cetylpyridinium chloride, chlorhexidine gluconate, phenoxyethanol; sodium hyaluronate, ceramide, collagen, placenta extract, mill
  • Moisturizing ingredients such as protein, vitamin C derivative, sorbit, gly
  • higher fatty acid esters such as isopropyl myristate and hexyl laurate; aloe, peach, touki, cordyceps, tomato, carrot, boucle, red grape, ashitaba, artea, arnica, diatom, cucumber, tea, burdock, shiitake, jiou, taiso,
  • plant extracts such as strawberry tea, phan, loofah, button, lily, apple, litchi; silicone, etc.
  • Examples of the pests that can be repelled in the present invention include various biting pests such as mosquitoes, flyfish, mites, fleas, flies, bedbugs, sardines, ticks, bees, ants, abs, and tsutsugamushi.
  • the present invention relates to the use of a polyalkylene glycol in which a polyalkylene glycol is applied to the skin together with a pest repellent in order to suppress penetration of the pest repellent into the skin.
  • a pest repellent composition having improved repellent effect and reduced skin irritation.
  • the insect repellent examples include various compounds as described above.
  • the pest repellent is usually 0.1 to 99.5 w / v%, more preferably 0.1 to 50 w / v%, still more preferably 0.5 to 50 w / v%, based on the pest repellent composition. Particularly preferred is 1 to 30 w / v%. If it is 1 w / v% or more, the sustaining effect is remarkable, and it is preferable, and if it is 30 w / v% or less, there is little stickiness.
  • the effective amount of polyalkylene glycol is preferably 0.1 to 99.5 w / v%, more preferably 0.1 to 50 w / v%, still more preferably 0.5 to 30 w / v based on the pest repellent composition. %, Particularly preferably 0.5 to 10 w / v%. If it is 0.5% w / v or more, it is preferable because the sustaining effect is remarkable, and if it is 10 w / v% or less, it is preferable because there is little stickiness.
  • the polyalkylene glycol content is preferably 0.025 or more, more preferably 0.05 or more in terms of mass ratio, when the pest repellent content is 1. preferable. It is because the effect which suppresses the penetration
  • the pest repellent composition can be used as various preparations such as a pump agent, a lotion agent, a wet tissue agent, a roll-on agent, a coating agent, and an aerosol agent as described above.
  • the preparation is made using a known carrier, propellant, solvent, emulsifying / dispersing agent, etc. as described above. What is necessary is just to make it a desired formulation form combining an actuator, an applicator, a pump apparatus, an aerosol apparatus, etc.
  • the present invention also provides a penetration inhibitor for pest repellents into the skin, which contains polyalkylene glycol. Since this penetration inhibitor contains polyalkylene glycol, the penetration of the pest repellent into the skin can be suppressed, and the pest repellent can be retained in the epidermis for a longer time.
  • Example 1 Skin absorption inhibition test >> ⁇ Test Example 1-1 (Examples 1 to 3, Comparative Example 1)> (Preparation of pest repellent composition)
  • each component was mixed under stirring to prepare a pest repellent composition (Examples 1 to 3, Comparative Example 1).
  • Deet's log P value is 2.0.
  • PEG-200 Micro Goal 200
  • PEG-1000 Micro Goal 1000
  • PP-1000 New Pole PP-1000
  • Test method The test was conducted according to the following procedure.
  • mold diffusion cell (The product made from a beadrex company, the horizontal-type palm cell for flat membranes) shown in FIG. 1 was used as a test apparatus.
  • Mouse skin 1 (lab skin, obtained from Hoshino Experimental Animal Breeding Co., Ltd.) was attached to the horizontal diffusion cell 10 so that the dermis side of the skin 1 was positioned on the receptor cell 2 side. 2.
  • About 45 ⁇ L of the prepared insect repellent composition was treated on the horny layer side (4.9 cm 2 ) of the skin 1, covered with aluminum foil 8, and the skin 1 was fixed with the tightening knob 6.
  • Receptor cell 2 was filled with 50 mL of saline 9 containing no diet. 4).
  • the receptor cell 2 stirs the physiological saline in the cell with the stirrer 3, and the heater / circulator 5 circulates hot water at 37 ° C. in the water jacket 4 covering the receptor cell 2,
  • the temperature in the receptor cell 2 was kept constant at 37 ° C. 5.
  • Sampling 3 mL of physiological saline 9 from the sampling port 7 of the receptor cell 2 0.5 hour and 1 hour after the temperature in the receptor cell 2 reached 37 ° C.
  • the saline solution was returned to make the liquid volume constant. 6).
  • the amount of diet in the sampling solution was measured by HPLC. From the measurement result of the diet amount, the residual amount on the skin and the residual rate on the skin were calculated by the following formula.
  • the residual amount on the skin (mg / cm 2 ) was a value obtained by rounding off the third decimal place, and the residual rate (%) on the skin was obtained by rounding off the first decimal place.
  • the results of Test Example 1-1 are shown in Table 2 (residual amount on skin (mg / cm 2 )) and Table 3 (residual rate on skin (%)).
  • Example 1-2 (Examples 4 to 8, Comparative Example 1)> A pest repellent composition was prepared according to the formulation shown in Table 4 below (Examples 4 to 8, Comparative Example 1), and a skin absorption inhibition test was conducted in the same manner as in Test Example 1-1.
  • Table 4 PP2000 (New Pole PP-2000) obtained from Sanyo Chemical Industries, Ltd. was used.
  • the results of Test Example 1-2 are shown in Table 5 (residual amount on skin (mg / cm 2 )) and Table 6 (residual rate on skin (%)).
  • Example 4 As can be seen from a comparison between Examples 4 to 8 and Comparative Example 1 of Test Example 1-1, the combined use of polypropylene glycol with diet results in the residual amount and residual rate of diet after a certain period of time. Resulted in more or more. Further, when the content of polypropylene glycol was increased, the residual amount and residual rate of the diet increased or increased depending on the concentration. Further, the pest of Example 4 having the lowest polypropyne glycol content relative to the deet content (the polypropyne glycol content is 0.05 by mass when the deet content is 1).
  • Example 9, Comparative Example 2 A pest repellent composition was prepared according to the formulation shown in Table 7 below (Example 9, Comparative Example 2), and a skin absorption inhibition test was conducted in the same manner as in Test Example 1-1.
  • Table 7 PP2000 (New Pole PP-2000) obtained from Sanyo Chemical Industries, Ltd. was used.
  • the results of Test Example 1-3 are shown in Table 8 (residual amount on skin (mg / cm 2 )) and Table 9 (residual rate on skin (%)).
  • Example 9 As can be seen from a comparison between Example 9 and Comparative Example 2, when polypropylene glycol is used in combination with diet, the amount and rate of residual diet on the skin after a certain period of time increase or increase. became.
  • Example 1-4 (Examples 10 to 11, Comparative Examples 3 to 4)> A pest repellent composition was prepared according to the formulation shown in Table 10 below (Examples 10 to 11 and Comparative Examples 3 to 4), and a skin absorption inhibition test was conducted in the same manner as in Test Example 1-1.
  • the log P value of menthol is 3.4
  • the log P value of p-menthane 3,8-diol is 1.4.
  • the results of Test Example 1-3 are shown in Table 11 (residual amount on skin (mg / cm 2 )) and Table 12 (residual rate on skin (%)).
  • Example 10 using a repellent and polypropylene glycol in combination resulted in a higher or higher residual amount and rate of pest repellent on the skin after a certain period of time.
  • p-menthane 3,8-diol was used as a pest repellent.
  • This result shows that even when the insect repellent menthol or p-menthane 3,8-diol is used instead of diet, these insect repellents can be used in the presence of a polymer such as polypropylene glycol rather than being applied to the skin alone. It was found that by applying a pest repellent to the skin in combination with alkylene glycol, the pest repellent remains on the skin for a longer time.
  • Test Example 1-5 (Reference Examples 1 to 4)> A pest repellent composition was prepared according to the formulation shown in Table 13 below (Reference Examples 1 to 4), and a skin absorption inhibition test was conducted in the same manner as in Test Example 1-1. The log P value of imidacloprid is 0.8, and the log P value of acetamiprid is 0.6. The results of Test Example 1-5 are shown in Table 14 (residual amount on skin (mg / cm 2 )) and Table 15 (residual rate on skin (%)).
  • the pest repellents (imidacloprid and acetamiprid) in the pest repellent compositions of Reference Examples 1 to 4 have a log P value of less than 1 and are difficult to penetrate the skin. There was no change in the residual amount and rate of pest repellent on the skin after the passage of.
  • Example 2 Bood Sucking Prevention Test
  • Example 2-1 Examples 12 to 14, Comparative Example 5
  • Example 12 has the same formulation as Example 6 in Test Example 1-2
  • Comparative Example 5 has the same formulation as Comparative Example 1 in Test Example 1-1.
  • Test method The test was conducted according to the following procedure. 1. Apply one piece of hairless mouse (male, 20-40 g) to the control group with ethanol, and the treated group with the insect pest repellent composition shown in Table 16 (0.5 mL treatment) to prevent movement into the wire mesh gauge. Fixed. 2. After suspending the gauge to which the mouse was fixed in the test box (30 cm ⁇ 30 cm ⁇ 30 cm), about 40 female female females were released into the cage. 3.
  • the results of Test Example 2-1 are shown in Table 17.
  • Examples 12 to 14 in which Diete and polyethylene glycol or polypropylene glycol are used in combination have the same amount of Diet compared to Comparative Example 5 in which Diete is used alone. Regardless, it was found that the blood sucking inhibition rate was significantly high for a certain period of time. As a result, the insect repellent of the insect repellent can be obtained by applying the insect repellent to the skin in combination with the polyalkylene glycol such as polyethylene glycol or polypropylene glycol, rather than applying the insect repellent such as diet alone to the skin. It was found that the sustainability of the effect was improved.
  • Example 2-2 (Examples 15 to 16, Comparative Example 6)> According to the formulation shown in Table 18 below, pest repellent compositions were prepared (Examples 15 to 16, Comparative Example 6) and tested according to the same procedure as in Test Example 2-1. The results of Test Example 2-2 are shown in Table 19.
  • Test Example 3 (Skin Irritation Inhibition Test) >>
  • the pest repellent composition of the present invention was applied to the skin of 10 subjects (5 men, 5 women; No. 1 to 10) to test whether the irritation to the skin of the pest repellent was suppressed. went.
  • Preparation of pest repellent composition [Examples 17 to 19, Comparative Example 7] According to the formulations shown in Tables 20 to 23 below, the components were mixed with stirring to prepare the pest repellent compositions of Examples 17 to 19 and Comparative Example 7.
  • decaglyceryl monooleate (decagulin 1-OV; available from Nikko Chemicals) was used as the glycerin fatty acid ester.
  • test drug sticking Each of the prepared test drugs (pest repellent compositions of Examples 17 to 19 and Comparative Example 7) and a control drug (purified water) were applied to a skin test patch tape (manufactured by Riba Tape Pharmaceutical Co., Ltd.). About 0.03 mL was dropped onto the pad and attached to the inner side of both upper arms of each subject. In addition, the density
  • evaluation points ( ⁇ : 0 point, ⁇ : 0.5 point, 1+: 1 point, 2+: 2 point, 3+: 3 point) were given to various determination results, and an average evaluation point was calculated. The results are shown in Table 25.
  • the pest repellent composition containing polypropylene glycol is less irritating to the skin than the case of not containing polypropylene glycol. Therefore, it was found that the irritation to the skin of the pest repellent can be suppressed by applying polyalkylene glycol to the skin together with the pest repellent.

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Abstract

The present invention addresses the problem of providing a method for inhibiting penetration of an insect pest repellant into the skin in order to improve the persistence of the insect pest repellent effect on the skin over a long period of time, with the chemical agent causing little irritation. The present invention provides a method for inhibiting penetration of an insect pest repellent effect into the skin by applying a polyalkylene glycol to the skin along with an insect pest repellant.

Description

害虫忌避剤の皮膚への浸透を抑制する方法及び害虫忌避剤の皮膚への浸透抑制剤Method for inhibiting penetration of pest repellent into skin and penetration inhibitor for pest repellent into skin
　本発明は、害虫忌避剤の皮膚への浸透を抑制する方法及び害虫忌避剤の皮膚への浸透抑制剤に関する。 The present invention relates to a method for suppressing penetration of a pest repellent into the skin and a penetration inhibitor for penetration of the pest repellent into the skin.
　従来、蚊をはじめとしたアブ、トコジラミなどの吸血昆虫からの被害を防ぐために、各種の害虫忌避剤が用いられてきた。これらの害虫忌避剤については、使用感の向上や刺激性の低減、忌避効果の持続性を高めるために各種検討がなされている。 Conventionally, various pest repellents have been used to prevent damage from blood-sucking insects such as mosquitoes, abs and bed bugs. About these pest repellents, various examinations are made in order to improve the feeling of use, reduce irritation, and increase the sustainability of the repellent effect.
　例えば、特許文献１には、害虫忌避成分による忌避効果を持続させるために、特定の無水ケイ酸粒子が配合された害虫忌避組成物が開示されている。また、特許文献２には、光による分解を抑えるために紫外線吸収剤を加えた害虫忌避組成物や、害虫忌避成分であるディートの刺激を抑えるために天然ミネラル水を併用した人体用害虫忌避剤が開示されている。 For example, Patent Document 1 discloses a pest repellent composition in which specific silicic acid particles are blended in order to maintain the repellent effect of the pest repellent component. Further, Patent Document 2 discloses a pest repellent composition containing an ultraviolet absorber for suppressing decomposition by light, and a human pest repellent which is combined with natural mineral water to suppress irritation of diet, which is a pest repellent component. Is disclosed.
日本国特開平９－２０８４０６号公報Japanese Unexamined Patent Publication No. 9-208406 日本国特開２００９－１２６８０４号公報Japanese Unexamined Patent Publication No. 2009-126804
　しかしながら、特許文献１の害虫忌避組成物においては、保管中に、配合した無水ケイ酸粒子が容器底部に沈降し、使用時にはその都度振り混ぜなくてはならない。そのため害虫忌避組成物を振り混ぜないで使用した場合には、噴口や塗布具の目詰まりや、噴射面、処理面に無水ケイ酸粒子が固まるなどの問題が生じる場合がある。 However, in the pest repellent composition of Patent Document 1, the blended silicic acid particles settle on the bottom of the container during storage and must be shaken each time it is used. Therefore, when the pest repellent composition is used without being shaken, problems such as clogging of the nozzle and applicator and solidification of silicic acid particles on the spray surface and treatment surface may occur.
　また、特許文献２の人体用害虫忌避剤においては、配合する天然ミネラル水の入手が容易とは言えず、安定して供給しづらいことから実用的ではないものである。 In addition, the pest repellent for human body of Patent Document 2 is not practical because it is not easy to obtain natural mineral water to be blended and it is difficult to supply stably.
　また、上記の害虫忌避組成物や害虫忌避剤を皮膚に適用する場合、害虫忌避剤が皮膚内部へ浸透するため、皮膚上に長時間にわたり害虫忌避剤を十分に滞留させることができない。そのため、皮膚に適用した害虫忌避剤の害虫忌避効果の持続性は不十分なものであった。さらに、ディート等の害虫忌避剤は皮膚刺激性を有するため、害虫忌避剤が皮膚内部へ浸透すると、皮膚に対して刺激を与えることになり、人体に適用する際の安全性は不十分であった。 In addition, when the above-mentioned pest repellent composition or pest repellent is applied to the skin, the pest repellent penetrates into the skin, so that the pest repellent cannot be sufficiently retained on the skin for a long time. Therefore, the persistence of the pest repellent effect of the pest repellent applied to the skin was insufficient. In addition, since pest repellents such as diet have skin irritation, if the pest repellent penetrates into the skin, it will irritate the skin, and safety when applied to the human body is insufficient. It was.
　そこで、本発明の課題は、薬剤による刺激が少なく、長時間に渡り、皮膚上における害虫忌避効果の持続性を向上させるために、害虫忌避剤の皮膚内部への浸透を抑制する方法を提供することにある。 Accordingly, an object of the present invention is to provide a method for suppressing penetration of a pest repellent into the skin in order to improve the sustainability of the pest repellent effect on the skin over a long period of time with less irritation by the drug. There is.
　本発明者は鋭意研究を重ねた結果、ポリアルキレングリコールを害虫忌避剤とともに皮膚に適用することにより、害虫忌避剤の皮膚内部への浸透を抑え、長時間にわたり害虫忌避剤を表皮（皮膚表面）に滞留させることができることを見出し、本発明を完成するに至った。 As a result of extensive research, the present inventor applied polyalkylene glycol to the skin together with a pest repellent to suppress penetration of the pest repellent into the skin, and the pest repellent was applied to the epidermis (skin surface) for a long time. The present invention has been completed.
　すなわち本発明は以下の通りである。
１．ポリアルキレングリコールを害虫忌避剤とともに皮膚に適用することにより、害虫忌避剤の皮膚への浸透を抑制する方法。
２．前記害虫忌避剤のｌｏｇＰ値が１以上である、前記１に記載の方法。
３．前記ポリアルキレングリコールの分子量が２００～２００００である前記１または２に記載の方法。
４．前記ポリアルキレングリコールが、ポリプロピレングリコールである、前記１～３のいずれか１に記載の方法。
５．ポリアルキレングリコールを含有する、害虫忌避剤の皮膚への浸透抑制剤。
６．ポリアルキレングリコールの、皮膚上に適用した害虫忌避剤の皮膚への浸透を抑制させるための使用。 That is, the present invention is as follows.
1. A method of suppressing penetration of a pest repellent into the skin by applying polyalkylene glycol to the skin together with the pest repellent.
2. 2. The method according to 1 above, wherein the pest repellent has a log P value of 1 or more.
3. 3. The method according to 1 or 2 above, wherein the polyalkylene glycol has a molecular weight of 200 to 20000.
4). 4. The method according to any one of 1 to 3, wherein the polyalkylene glycol is polypropylene glycol.
5. A pest repellent penetration inhibitor for skin containing polyalkylene glycol.
6). Use of polyalkylene glycol to suppress penetration of a pest repellent applied on the skin into the skin.
　本発明によれば、害虫忌避剤を皮膚に適用する際に、ポリアルキレングリコールを合わせて適用することで、害虫忌避剤の皮膚内部への浸透を抑えることができる。その結果、害虫忌避剤を皮膚上に長時間にわたり滞留させることが可能となり、皮膚上における害虫忌避効果の持続性を向上させることができる。 According to the present invention, when the pest repellent is applied to the skin, the penetration of the pest repellent into the skin can be suppressed by applying the polyalkylene glycol together. As a result, the pest repellent can be retained on the skin for a long time, and the sustainability of the pest repellent effect on the skin can be improved.
　さらに、害虫忌避剤を低濃度で用いても害虫忌避効果を長時間持続させることができ、人体への刺激の少ない製剤を提供することができる。また、害虫忌避剤を高濃度で用いた場合においては、害虫忌避剤の皮膚内部への浸透を抑えることができるので、害虫忌避剤の皮膚に対する刺激を抑制することができ、人体に対してより安全性が高い製剤を提供することができる。 Furthermore, even if a pest repellent is used at a low concentration, the pest repellent effect can be maintained for a long time, and a preparation with less irritation to the human body can be provided. In addition, when the pest repellent is used at a high concentration, the penetration of the pest repellent into the skin can be suppressed, so that the irritation to the skin of the pest repellent can be suppressed, and more to the human body. A highly safe formulation can be provided.
図１は、皮膚吸収抑制試験に用いた水平型拡散セルの模式図である。FIG. 1 is a schematic diagram of a horizontal diffusion cell used in a skin absorption inhibition test.
　以下、本発明をさらに詳細に説明する。 Hereinafter, the present invention will be described in more detail.
　本発明は、ポリアルキレングリコールを害虫忌避剤とともに皮膚に適用することにより、害虫忌避剤の皮膚への浸透を抑制する方法を提供するものである。また、本発明は、ポリアルキレングリコールの、皮膚上に適用した害虫忌避剤の皮膚への浸透を抑制させるための使用方法を提供するものである。 The present invention provides a method for suppressing penetration of a pest repellent into the skin by applying polyalkylene glycol to the skin together with the pest repellent. The present invention also provides a method for using polyalkylene glycol to suppress penetration of a pest repellent applied on the skin into the skin.
　本発明の害虫忌避剤としては、刺咬性害虫に対して忌避作用又は吸血阻害作用を有する、合成又は天然の各種化合物を用いることができる。例えば、Ｎ，Ｎ－ジエチル－ｍ－トルアミド（以下、ディートともいう）、ｐ－メンタン－３，８－ジオール、３－（Ｎ－アセチル－ｎ－ブチル）アミノプロピオン酸エチルエステル、２－（２－ヒドロキシエチル）－１－ピペリジンカルボン酸１－メチルプロピル、２－エチル－１，３－ヘキサジオール、ブチル３，４－ジヒドロ－２，２－ジメチル－４－オキソ－２Ｈ－ピラン－６－カルボキシレート、ｎ－ヘキシルトリエチレングリコールモノエーテル、メチル６－ｎ－ペンチル－シクロヘキセン－１－カルボキシレート、ジメチルフタレート、ユーカリプトール、メントール、酢酸メンチル、α－ピネン、ゲラニオール、シトロネラール、シトロネロール、シトラール、ターピネオール、カンファー、リナロール、テルペノール、カルボン、フタル酸ジオクチル、フタル酸ジブチル、ナフタレンなどが挙げられる。 As the pest repellent of the present invention, various synthetic or natural compounds having a repellent action or blood sucking inhibitory action against biting pests can be used. For example, N, N-diethyl-m-toluamide (hereinafter also referred to as diet), p-menthane-3,8-diol, 3- (N-acetyl-n-butyl) aminopropionic acid ethyl ester, 2- (2 -Hydroxyethyl) -1-piperidinecarboxylic acid 1-methylpropyl, 2-ethyl-1,3-hexadiol, butyl 3,4-dihydro-2,2-dimethyl-4-oxo-2H-pyran-6-carboxy Rate, n-hexyltriethylene glycol monoether, methyl 6-n-pentyl-cyclohexene-1-carboxylate, dimethyl phthalate, eucalyptol, menthol, menthyl acetate, α-pinene, geraniol, citronellal, citronellol, citral, terpineol , Camphor, linalool, terpenol, ca Bonn, dioctyl phthalate, dibutyl phthalate, and naphthalene.
　この他にも、例えば、シトロネラ、ペパーミント、シダーウッド、ラベンダー、ティートゥリーオイル、桂皮、樟脳、レモングラス、クローバ、タチジャコウソウ、ジェラニウム、ベルガモント、月桂樹、松、アカモモ、ベニーロイアル、ユーカリ、インドセダンなどから抽出される精油やエキス、さらには、ピレトリン、アレスリン、フタルスリン、レスメトリン、フラメトリン、フェノトリン、ペルメトリン、シフェノトリン、プラレトリン、エトフェンプロックス、エムペントリン、トランスフルスリン、メトフルトリン、プロフルトリンなどのピレスロイド系化合物などを用いることができる。 In addition, for example, Citronella, peppermint, cedarwood, lavender, tea tree oil, cinnamon bark, camphor, lemongrass, clover, ginger, geranium, bergamont, laurel, pine, red peach, Benny royal, eucalyptus, Indian sedan, etc. Extracted essential oils and extracts, as well as pyrethroids such as pyrethrin, allethrin, phthalthrin, resmethrin, flamethrin, phenothrin, permethrin, ciphenothrin, praretrin, etofenprox, empentrin, transfluthrin, methfluthrin, profluthrin, etc. be able to.
　これらの害虫忌避剤は、１種または２種以上を組み合わせて用いることができ、これらの中でも汎用性が高いという観点から、ディートが好ましい。 These pest repellents can be used singly or in combination of two or more, and among these, diet is preferred from the viewpoint of high versatility.
　本発明の害虫忌避剤は、ｌｏｇＰ値が１以上であることが好ましい。 The pest repellent of the present invention preferably has a log P value of 1 or more.
　本発明において、ｌｏｇＰ値とは、Ｃｈｅｍｉｃａｌ　Ｒｅｖｉｅｗｓ　ｖｏｌ７１（６），５２５（１９７１）などで定義されている水とオクタノールへの物質の分配のしやすさにより、極性をあらわす係数である。薬剤のｌｏｇＰ値は、計算ソフト（ＰＡＬＡＡＳ：ＣｏｍｐＤｒｕｇ　Ｃｈｅｍｉｓｔｒｙ　Ｌｔｄ．製）にて算出することができる。 In the present invention, the log P value is a coefficient representing polarity depending on the ease of distribution of a substance between water and octanol, which is defined in Chemical Reviews vol 71 (6), 525 (1971). The log P value of the drug can be calculated by calculation software (PALAAS: manufactured by CompDrug Chemistry Ltd.).
　ｌｏｇＰ値は大きいほど、疎水表面である皮膚の角層との親和性が良くなり、皮膚へ浸透しやすくなることが知られている。ｌｏｇＰ値が１以上である害虫忌避剤は、疎水性の角層との親和性が良いので角層表面上でのぬれが良い。そのため、皮膚への浸透面積が大きくなる。皮膚への浸透は害虫忌避剤と皮膚との浸透面積に比例するので、浸透面積が大きいと浸透量も多くなる。 It is known that the larger the logP value, the better the affinity with the stratum corneum of the skin, which is a hydrophobic surface, and the easier it is to penetrate into the skin. A pest repellent having a log P value of 1 or more has good affinity with a hydrophobic stratum corneum, and therefore has good wettability on the stratum corneum surface. Therefore, the penetration area into the skin increases. Since the penetration into the skin is proportional to the penetration area between the pest repellent and the skin, the larger the penetration area, the greater the penetration amount.
　したがって、ｌｏｇＰ値が１以上であり、皮膚への浸透量が多い害虫忌避剤である程、後述するポリアルキレングリコールによる害虫忌避剤の皮膚への浸透を抑制する本発明の効果がより顕著に得られることとなるため、好ましい。 Therefore, the effect of the present invention that suppresses the penetration of the pest repellent into the skin by the polyalkylene glycol described later is more prominent as the pest repellent has a log P value of 1 or more and the amount of penetration into the skin. Therefore, it is preferable.
　本発明では、前記害虫忌避剤とともに、ポリアルキレングリコールを皮膚に適用する。ポリアルキレングリコールを害虫忌避剤とともに皮膚に適用することにより、害虫忌避剤の皮膚内部への浸透を抑えることができる。 In the present invention, polyalkylene glycol is applied to the skin together with the pest repellent. By applying polyalkylene glycol to the skin together with a pest repellent, penetration of the pest repellent into the skin can be suppressed.
　また、ポリアルキレングリコールを皮膚に適用することにより害虫忌避剤の皮膚内部への浸透を抑えることができるので、害虫忌避剤をより長時間皮膚上に滞留させることができ、その結果皮膚上における害虫忌避剤の害虫忌避効果の持続性を向上させることができる。したがって本発明は、ポリアルキレングリコールを害虫忌避剤とともに皮膚に適用することにより、害虫忌避剤の皮膚への浸透を抑制し、皮膚上における害虫忌避剤の害虫忌避効果の持続性を向上させる方法も提供するものである。 Moreover, since the penetration of the pest repellent into the skin can be suppressed by applying polyalkylene glycol to the skin, the pest repellent can be retained on the skin for a longer time, and as a result, the pest repellent on the skin. The persistence of the insect repellent effect of the repellent can be improved. Therefore, the present invention also includes a method of suppressing the penetration of the pest repellent into the skin by applying polyalkylene glycol to the skin together with the pest repellent and improving the persistence of the pest repellent effect of the pest repellent on the skin. It is to provide.
　また、ポリアルキレングリコールを皮膚に適用することにより害虫忌避剤の皮膚内部への浸透を抑えることができるので、害虫忌避剤の皮膚に対する刺激を抑制することができる。したがって本発明は、ポリアルキレングリコールを害虫忌避剤とともに皮膚に適用することにより、害虫忌避剤の皮膚への浸透を抑制し、害虫忌避剤の皮膚に対する刺激を抑制する方法も提供するものである。 Moreover, since the penetration of the pest repellent into the skin can be suppressed by applying polyalkylene glycol to the skin, irritation to the skin of the pest repellent can be suppressed. Therefore, the present invention also provides a method for suppressing the penetration of a pest repellent into the skin and applying the pest repellent to the skin by applying the polyalkylene glycol to the skin together with the pest repellent.
　ポリアルキレングリコールを害虫忌避剤とともに皮膚に適用することにより、害虫忌避剤の皮膚内部への浸透を抑えることができる作用機序は明らかではないが、ポリアルキレングリコールのアルキレン鎖部位に害虫忌避剤が保持され、害虫忌避剤の皮膚内部への浸透を抑制するためだと推測される。 Although the mechanism of action that can suppress the penetration of the pest repellent into the skin by applying the polyalkylene glycol to the skin together with the pest repellent is not clear, there is no pest repellent at the alkylene chain site of the polyalkylene glycol. It is presumed to be retained and to suppress penetration of the pest repellent into the skin.
　前記ポリアルキレングリコールの分子量としては、好ましくは２００～２００００であり、より好ましくは２００～５０００である。ポリアルキレングリコールの分子量が２００以上であると効果が顕著であるため好ましく、２００００以下であると製剤調製が容易となるため好ましい。 The molecular weight of the polyalkylene glycol is preferably 200 to 20000, more preferably 200 to 5000. When the molecular weight of the polyalkylene glycol is 200 or more, it is preferable because the effect is remarkable.
　また、ポリアルキレングリコールの重合度は好ましくは３以上、より好ましくは４～４００である。ポリアルキレングリコールの重合度が３以上であると本発明の効果が十分に得られるため好ましく、４以上であるとその効果がより顕著になるため好ましい。また、重合度が４００以下のポリアルキレングリコールは汎用性が高いため好ましい。 Also, the degree of polymerization of the polyalkylene glycol is preferably 3 or more, more preferably 4 to 400. When the degree of polymerization of the polyalkylene glycol is 3 or more, the effect of the present invention is sufficiently obtained, and when it is 4 or more, the effect becomes more remarkable. A polyalkylene glycol having a polymerization degree of 400 or less is preferable because of its high versatility.
　また、ポリアルキレングリコールの炭素数は２～４のものが好ましく、２～３がより好ましい。ポリアルキレングリコールの炭素数が２以上であると本発明の効果が顕著であるため好ましく、４以下であると害虫忌避組成物とする際に各種成分との相溶性が高いため好ましい。 The polyalkylene glycol preferably has 2 to 4 carbon atoms, more preferably 2 to 3 carbon atoms. When the carbon number of the polyalkylene glycol is 2 or more, the effect of the present invention is remarkable, and when it is 4 or less, it is preferable because the compatibility with various components is high when the pest repellent composition is used.
　また、ポリアルキレングリコールは直鎖であっても分岐鎖であってもよい。具体的には、ポリプロピレングリコールおよびポリエチレングリコール等が挙げられる。汎用性、安定性および皮膚への低刺激性の観点から、ポリプロピレングリコールおよびポリエチレングリコールが好ましく、ポリプロピレングリコールが特に好ましい。また、種々のポリアルキレングリコールを１種単独で用いてもよく、２種以上を組合せて用いることもできる。 The polyalkylene glycol may be linear or branched. Specific examples include polypropylene glycol and polyethylene glycol. From the viewpoints of versatility, stability and mildness to skin, polypropylene glycol and polyethylene glycol are preferable, and polypropylene glycol is particularly preferable. Various polyalkylene glycols may be used alone or in combination of two or more.
　本発明において好適なポリアルキレングリコールとしては、例えば、ポリエチレングリコール２００、ポリエチレングリコール４００、ポリエチレングリコール６００、ポリエチレングリコール８００、ポリエチレングリコール１０００、ポリプロピレングリコール１０００、ポリプロピレングリコール２０００、及びポリプロピレングリコール４０００等が挙げられる。 Examples of suitable polyalkylene glycol in the present invention include polyethylene glycol 200, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 800, polyethylene glycol 1000, polypropylene glycol 1000, polypropylene glycol 2000, and polypropylene glycol 4000.
　ポリアルキレングリコールを害虫忌避剤とともに皮膚に適用するに際しては、害虫忌避剤の適用量を１としたときのポリアルキレングリコールの適用量が質量比で０．０２５以上であることが好ましく、０．０５以上であることがより好ましい。上記範囲であることで、ポリアルキレングリコールの害虫忌避剤の皮膚への浸透を抑制する効果がより高くなるからである。 When the polyalkylene glycol is applied to the skin together with the pest repellent, the applied amount of the polyalkylene glycol when the applied amount of the pest repellent is 1 is preferably 0.025 or more by mass ratio, 0.05 More preferably. It is because the effect which suppresses the penetration | invasion to the skin of the pest repellent of polyalkylene glycol becomes higher because it is the said range.
　ポリアルキレングリコールを害虫忌避剤とともに皮膚に適用するに際しては、害虫忌避剤及びポリアルキレングリコールの両者を同時に適用してもよいし、別々に分けて適用してもよい。皮膚全体に塗り延ばしやすい点、ディートなどの害虫忌避剤の刺激が緩和される点、さらには簡便性の観点から、両者を含有する製剤として同時に皮膚に適用することが好ましい。 When the polyalkylene glycol is applied to the skin together with the pest repellent, both the pest repellent and the polyalkylene glycol may be applied simultaneously, or may be applied separately. From the viewpoint of easy spreading on the entire skin, the stimulation of pest repellents such as diet, etc. being alleviated, and from the viewpoint of simplicity, it is preferable to apply both to the skin at the same time.
　前記害虫忌避剤及びポリアルキレングリコールを皮膚に適用するに際しては、例えば、ポンプ剤、ローション剤、ウェットティッシュ剤、ロールオン剤、塗布剤、エアゾール剤等の各種製剤として皮膚に適用することができる。 When applying the above-mentioned pest repellent and polyalkylene glycol to the skin, it can be applied to the skin as various preparations such as a pump agent, a lotion agent, a wet tissue agent, a roll-on agent, a coating agent, an aerosol agent, and the like.
　これらの製剤とするには、本発明の効果を奏する限りにおいて、公知の担体、噴射剤、溶剤、乳化・分散剤等を用いて調製し、さらに必要に応じて、不織布、アクチュエーター、塗布具、ポンプ装置、エアゾール装置等と組合せて所望の製剤形態とすればよい。 In order to obtain these preparations, as long as the effects of the present invention are exhibited, the preparation is prepared using a known carrier, propellant, solvent, emulsifying / dispersing agent, etc., and if necessary, a nonwoven fabric, an actuator, an applicator, What is necessary is just to make it a desired formulation form combining with a pump apparatus, an aerosol apparatus, etc.
　前記害虫忌避剤及びポリアルキレングリコールを皮膚上に適用するに際しては、例えば、害虫忌避剤がディートである場合、ディートの皮膚への付着量が１．５ｍｇ／１００ｃｍ２以上、かつポリアルキレングリコールの皮膚への付着量が０．３ｍｇ／１００ｃｍ２以上となるように適用するのが好ましい。ディート及びポリアルキレングリコールの皮膚への付着量を前記範囲とすることで、害虫忌避効果及び皮膚への浸透抑制効果を十分に得ることができる。 When the pest repellent and the polyalkylene glycol are applied to the skin, for example, when the pest repellent is a diet, the amount of the diet attached to the skin is 1.5 mg / 100 cm 2 or more, and the polyalkylene glycol skin It is preferable to apply so that the amount of adhesion to the surface becomes 0.3 mg / 100 cm 2 or more. By making the adhesion amount of the diet and polyalkylene glycol to the skin within the above range, a pest repellent effect and a skin penetration inhibiting effect can be sufficiently obtained.
　さらに、良好な使用感を得るという観点から、ディートは１．５～１５０ｍｇ／１００ｃｍ２、ポリアルキレングリコールは０．３～５０ｍｇ／１００ｃｍ２の付着量で用いることがより好ましい。この好ましい条件を得るためには、例えば、皮膚に適用する際にエアゾール剤やポンプ剤を使用する場合には、噴口、バルブ、噴射圧などを調整したり、塗布剤、ロールオン剤やウェットティッシュ剤を使用する場合においては、塗布面形状や塗布部の材質性状などを調整するなどして、皮膚への害虫忌避剤及びポリアルキレングリコールの付着量を調整すればよい。 Further, from the standpoint of obtaining a good feeling of use, it is more preferable to use a deposit of 1.5 to 150 mg / 100 cm 2 for diet and 0.3 to 50 mg / 100 cm 2 for polyalkylene glycol. In order to obtain this preferable condition, for example, when an aerosol agent or a pump agent is used when applied to the skin, a nozzle, a valve, an injection pressure, etc. are adjusted, a coating agent, a roll-on agent or a wet tissue agent. In the case of using, the adhesion amount of the pest repellent and the polyalkylene glycol to the skin may be adjusted by adjusting the shape of the coated surface or the material property of the coated part.
　前記製剤をエアゾール剤として皮膚に適用するには、製剤全体に対して噴射剤が５～９５ｖ／ｖ％となるようにエアゾール容器に加圧充填すればよい。噴射剤としては、例えば、液化石油ガス、ジメチルエーテル、代替フロン、圧縮ガス（酸素、窒素）、及びこれらの混合物等を用いることができる。 In order to apply the preparation to the skin as an aerosol, the aerosol container may be pressurized and filled so that the propellant is 5 to 95 v / v% with respect to the whole preparation. As the propellant, for example, liquefied petroleum gas, dimethyl ether, alternative chlorofluorocarbon, compressed gas (oxygen, nitrogen), and a mixture thereof can be used.
　また前記製剤をウェットティッシュ剤として皮膚に適用するには、支持体の目付量が２０～８０ｇ／ｍ２であることが好ましい。支持体の目付量が２０～８０ｇ／ｍ２であることによって所望の害虫忌避剤及びポリアルキレングリコールの取り込み、保持、塗布、含浸が可能になる。 In order to apply the preparation to the skin as a wet tissue agent, the basis weight of the support is preferably 20 to 80 g / m 2 . When the basis weight of the support is 20 to 80 g / m 2 , the desired pest repellent and polyalkylene glycol can be taken in, retained, applied and impregnated.
　また、厚さが０．１～５ｍｍ程度の支持体に、害虫忌避剤を７０～３００ｍｌ／ｍ２保持させることが好ましい。害虫忌避剤を支持体に７０～３００ｍｌ／ｍ２保持させることによって、所望の害虫忌避剤及びポリアルキレングリコールの取り込み、保持、塗布、含浸が可能になる。 Further, it is preferable to hold the pest repellent at 70 to 300 ml / m 2 on a support having a thickness of about 0.1 to 5 mm. By holding the pest repellent on the support at 70 to 300 ml / m 2 , the desired pest repellent and polyalkylene glycol can be taken in, retained, applied and impregnated.
　支持体としては、ネル、綿、絹、ポリエステル、ナイロン、これらを素材としたもの等の織布；ポリエステル、ポリオレフィン、ナイロン、綿、レーヨン、ビニロン、セルロース、これらを素材としたもの等の不織布；ポリエチレン、ポリプロピレン、エチレン－酢酸ビニル共重合体、ポリ塩化ビニル等を発泡させたシート状の樹脂発泡体等を用いることができる。 As a support, woven fabric such as flannel, cotton, silk, polyester, nylon, or the like made from these materials; non-woven fabric such as polyester, polyolefin, nylon, cotton, rayon, vinylon, cellulose, or the like made from these materials; A sheet-like resin foam obtained by foaming polyethylene, polypropylene, ethylene-vinyl acetate copolymer, polyvinyl chloride, or the like can be used.
　担体としては、例えば、水道水、精製水、イオン水等の水、エチルアルコール、イソプロピルアルコール、ラウリルアルコール、セタノール、２－ヘキシルデカノール、ステアリルアルコール、イソステアリルアルコール、オレイルアルコール、ラノリンアルコール等の低級アルコール、エチレングリコール、ジエチレングリコールモノエチルエーテル、トリエチレングリコール、プロピレングリコール、１，３－ブチレングリコール、グリセリン等の多価アルコール、炭化水素系溶剤等が挙げられる。 Examples of the carrier include water such as tap water, purified water, ionic water, ethyl alcohol, isopropyl alcohol, lauryl alcohol, cetanol, 2-hexyldecanol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, lanolin alcohol, and other lower alcohols, Examples thereof include polyhydric alcohols such as ethylene glycol, diethylene glycol monoethyl ether, triethylene glycol, propylene glycol, 1,3-butylene glycol and glycerin, and hydrocarbon solvents.
　乳化・分散剤としては、例えば、ソルビタントリオレート、ポリオキシエチレンモノオレート、ポリオキシエチレンアルキルエーテル、ポリオキシエチレンノニルフェニルエーテル、ポリオキシエチレン硬化ヒマシ油、ポリオキシエチレンアルキルエーテル、デカグリセリンモノオレート、ジオレイン酸プロピレングリコール、ポリオキシエチレンステアリン酸アミド、ポリオキシエチレンラウリルエーテルリン酸、グリセリン脂肪酸エステル、ステアリルアルコール、ポリビニルピロリドン、ラノリン脂肪酸等の界面活性剤、低級アルコール、多価アルコール等が挙げられる。 Examples of the emulsifying / dispersing agent include sorbitan trioleate, polyoxyethylene monooleate, polyoxyethylene alkyl ether, polyoxyethylene nonylphenyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, decaglycerin monooleate, Examples include surfactants such as propylene glycol dioleate, polyoxyethylene stearamide, polyoxyethylene lauryl ether phosphate, glycerin fatty acid ester, stearyl alcohol, polyvinyl pyrrolidone, and lanolin fatty acid, lower alcohols, and polyhydric alcohols.
　さらに使用感を向上させたり、害虫忌避効果を高めたり、殺菌効果を付与する等を目的として、例えば、任意の量の粉体、香料成分、殺菌・防腐成分、保湿成分、増粘剤等をあわせて皮膚に適用することができる。 For the purpose of further improving the feeling of use, enhancing the repellent effect of pests, imparting a bactericidal effect, etc., for example, any amount of powder, fragrance component, bactericidal / preservative component, moisturizing component, thickener, etc. It can also be applied to the skin.
　例えば、疎水性シリカ、ケイ酸カルシウム、ケイソウ土、高純度シリカ、無水ケイ酸等のケイ酸化合物；タルク、炭酸カルシウム、ステアリン酸マグネシウム、酸性白土、ホワイトカーボン、パーライト等の無機粉体；オクテニルコハク酸トウモロコシデンプンエステルアルミニウム等のアルケニルコハク酸デンプンの金属塩；シルクパウダー等の天然パウダー；ナイロン、ポリプロピレン等の樹脂等の粉体；メントール、ハッカオイル、ミントオイル等の香料成分；フェノール、パラオキシ安息香酸エステル、サリチル酸及びその塩、塩化ベンザルコニウム、塩化セチルピリジニウム、グルコン酸クロルヘキシジン、フェノキシエタノール等の殺菌・防腐成分；ヒアルロン酸ナトリウム、セラミド、コラーゲン、プラセンタエキス、ミルクプロテイン、ビタミンＣ誘導体、ソルビット、グリセリン等の保湿成分（湿潤剤）；カルボキシビニルポリマー、３－オクタデシルオキシ－２－ヒドロキシプロピル２－ヒドロキシプロピルメチルセルロース等の増粘剤；パラアミノ安息香酸エステル、シノキサート、オキシベンゼン等の紫外線吸収・遮断成分；クロルヒドロキシアルミニウム、アルミニウム・ジルコニウムクロルヒドレート等の制汗・消臭成分；ベニバナ等の色素成分等が挙げられる。 For example, silica compounds such as hydrophobic silica, calcium silicate, diatomaceous earth, high-purity silica, and anhydrous silicic acid; inorganic powders such as talc, calcium carbonate, magnesium stearate, acid clay, white carbon, pearlite; octenyl succinic acid Metal salt of alkenyl succinate starch such as corn starch ester aluminum; Natural powder such as silk powder; Powder such as resin such as nylon and polypropylene; Fragrance ingredients such as menthol, mint oil, mint oil; Phenol, paraoxybenzoic acid ester Bactericidal and antiseptic components such as salicylic acid and its salts, benzalkonium chloride, cetylpyridinium chloride, chlorhexidine gluconate, phenoxyethanol; sodium hyaluronate, ceramide, collagen, placenta extract, mill Moisturizing ingredients (wetting agents) such as protein, vitamin C derivative, sorbit, glycerin; thickeners such as carboxyvinyl polymer, 3-octadecyloxy-2-hydroxypropyl 2-hydroxypropylmethylcellulose; paraaminobenzoic acid ester, synoxate, oxy Examples include ultraviolet ray absorbing / blocking components such as benzene; antiperspirant / deodorant components such as chlorohydroxyaluminum and aluminum / zirconium chlorohydrate; and pigment components such as safflower.
　さらにミリスチン酸イソプロピル、ラウリン酸ヘキシル等の高級脂肪酸エステル；アロエ、モモ、トウキ、冬虫夏草、トマト、ニンジン、ブクリョウ、アカブドウ、アシタバ、アルテア、アルニカ、カイソウ、キューカンバ、紅茶、ゴボウ、シイタケ、ジオウ、タイソウ、甜茶、プハーン、ヘチマ、ボタン、ユリ、リンゴ、レイシ等の植物抽出物；シリコーン等を配合することにより、害虫忌避効果の持続と使用感の更なる向上を図ることができる。 In addition, higher fatty acid esters such as isopropyl myristate and hexyl laurate; aloe, peach, touki, cordyceps, tomato, carrot, boucle, red grape, ashitaba, artea, arnica, diatom, cucumber, tea, burdock, shiitake, jiou, taiso, By blending plant extracts such as strawberry tea, phan, loofah, button, lily, apple, litchi; silicone, etc., the pest repellent effect can be maintained and the feeling of use can be further improved.
　本発明において忌避の対象となりうる害虫としては、例えば、カ、ブユ、ダニ、ノミ、サシバエ、ナンキンムシ、ヤマビル、マダニ、ハチ、アリ、アブ、ツツガムシ等の各種の刺咬性害虫が挙げられる。 Examples of the pests that can be repelled in the present invention include various biting pests such as mosquitoes, flyfish, mites, fleas, flies, bedbugs, sardines, ticks, bees, ants, abs, and tsutsugamushi.
　本発明は、害虫忌避剤の皮膚内部への浸透を抑えるためにポリアルキレングリコールを害虫忌避剤とともに皮膚に適用するという、ポリアルキレングリコールの用途に関するものであり、本発明を適用することで、害虫忌避効果の持続性が向上し、かつ皮膚に対する刺激が抑制された害虫忌避組成物が提供される。 The present invention relates to the use of a polyalkylene glycol in which a polyalkylene glycol is applied to the skin together with a pest repellent in order to suppress penetration of the pest repellent into the skin. By applying the present invention, the pest There is provided a pest repellent composition having improved repellent effect and reduced skin irritation.
　害虫忌避剤としては、前述したような各種化合物が挙げられる。害虫忌避剤は、害虫忌避組成物に対して、通常、０．１～９９．５ｗ／ｖ％、より好ましくは０．１～５０ｗ／ｖ％、さらに好ましくは０．５～５０ｗ／ｖ％、特に好ましくは１～３０ｗ／ｖ％である。１ｗ／ｖ％以上であると、持続効果が顕著であるため好ましく、３０ｗ／ｖ％以下であると、べたつきが少ないため好ましい。 Examples of the insect repellent include various compounds as described above. The pest repellent is usually 0.1 to 99.5 w / v%, more preferably 0.1 to 50 w / v%, still more preferably 0.5 to 50 w / v%, based on the pest repellent composition. Particularly preferred is 1 to 30 w / v%. If it is 1 w / v% or more, the sustaining effect is remarkable, and it is preferable, and if it is 30 w / v% or less, there is little stickiness.
　皮膚における害虫忌避効果の持続性を向上させる効果を得るためには、有効量のポリアルキレングリコールを皮膚上に適用する必要がある。ポリアルキレングリコールの有効量として好ましくは、害虫忌避組成物に対して０．１～９９．５ｗ／ｖ％、より好ましくは０．１～５０ｗ／ｖ％、さらに好ましくは０．５～３０ｗ／ｖ％、特に好ましくは０．５～１０ｗ／ｖ％である。０．５％ｗ／ｖ以上であると、持続効果が顕著であるため好ましく、１０ｗ／ｖ％以下であると、べたつきが少ないため好ましい。 In order to obtain the effect of improving the sustainability of the pest repellent effect on the skin, it is necessary to apply an effective amount of polyalkylene glycol on the skin. The effective amount of polyalkylene glycol is preferably 0.1 to 99.5 w / v%, more preferably 0.1 to 50 w / v%, still more preferably 0.5 to 30 w / v based on the pest repellent composition. %, Particularly preferably 0.5 to 10 w / v%. If it is 0.5% w / v or more, it is preferable because the sustaining effect is remarkable, and if it is 10 w / v% or less, it is preferable because there is little stickiness.
　上記害虫忌避組成物においては、害虫忌避剤の含有量を１としたときのポリアルキレングリコールの含有量が、質量比で０．０２５以上であることが好ましく、０．０５以上であることがより好ましい。上記範囲であることで、ポリアルキレングリコールの害虫忌避剤の皮膚への浸透を抑制する効果がより高くなるからである。 In the pest repellent composition, the polyalkylene glycol content is preferably 0.025 or more, more preferably 0.05 or more in terms of mass ratio, when the pest repellent content is 1. preferable. It is because the effect which suppresses the penetration | invasion to the skin of the pest repellent of polyalkylene glycol becomes higher because it is the said range.
　上記害虫忌避組成物は、前述したような、ポンプ剤、ローション剤、ウェットティッシュ剤、ロールオン剤、塗布剤、エアゾール剤等の各種製剤として用いることができる。 The pest repellent composition can be used as various preparations such as a pump agent, a lotion agent, a wet tissue agent, a roll-on agent, a coating agent, and an aerosol agent as described above.
　これらの製剤とするには、本発明の効果が奏する限りにおいて、前述したような、公知の担体、噴射剤、溶剤、乳化・分散剤等を用いて調製し、さらに必要に応じて、不織布、アクチュエーター、塗布具、ポンプ装置、エアゾール装置等と組合せて所期の製剤形態とすればよい。 In order to obtain these preparations, as long as the effects of the present invention are exhibited, the preparation is made using a known carrier, propellant, solvent, emulsifying / dispersing agent, etc. as described above. What is necessary is just to make it a desired formulation form combining an actuator, an applicator, a pump apparatus, an aerosol apparatus, etc.
　本発明はまた、ポリアルキレングリコールを含有する、害虫忌避剤の皮膚への浸透抑制剤を提供するものである。この浸透抑制剤は、ポリアルキレングリコールを含有しているため、害虫忌避剤の皮膚内部への浸透を抑え、害虫忌避剤をより長時間表皮に滞留させることができる。 The present invention also provides a penetration inhibitor for pest repellents into the skin, which contains polyalkylene glycol. Since this penetration inhibitor contains polyalkylene glycol, the penetration of the pest repellent into the skin can be suppressed, and the pest repellent can be retained in the epidermis for a longer time.
　以下、実施例および比較例により本発明をさらに説明するが、本発明は下記例に何ら制限されるものではない。 Hereinafter, the present invention will be further described with reference to examples and comparative examples, but the present invention is not limited to the following examples.
＜＜試験例１：皮膚吸収抑制試験）＞＞
＜試験例１－１（実施例１～３、比較例１）＞
（害虫忌避組成物の調製）
　下記表１に示す処方に従い、各成分を撹拌下で混合して、害虫忌避組成物を調製した（実施例１～３、比較例１）。なお、ディートのｌｏｇＰ値は２．０である。またＰＥＧ－２００（マクロゴール２００）、ＰＥＧ－１０００（マクロゴール１０００）、及びＰＰ－１０００（ニューポールＰＰ－１０００）は、三洋化成工業株式会社から入手したものを用いた。 << Test Example 1: Skin absorption inhibition test >>
<Test Example 1-1 (Examples 1 to 3, Comparative Example 1)>
(Preparation of pest repellent composition)
According to the formulation shown in Table 1 below, each component was mixed under stirring to prepare a pest repellent composition (Examples 1 to 3, Comparative Example 1). Deet's log P value is 2.0. In addition, PEG-200 (Macro Goal 200), PEG-1000 (Macro Goal 1000), and PP-1000 (New Pole PP-1000) were obtained from Sanyo Chemical Industries, Ltd.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
（試験方法）
　以下の手順により試験を行った。なお、試験装置として、図１に示す水平型拡散セル（ビードレックス社製、平板膜用水平型パームセル）を使用した。
１．マウスの皮膚１（ラボスキン、株式会社星野実験動物飼育所より入手）を水平型拡散セル１０に、皮膚１の真皮側がレセプターセル２側に位置するように取り付けた。
２．皮膚１の角層側（４．９ｃｍ２）に、上記調製した害虫忌避組成物を約４５μＬ処理し、アルミ箔８で覆い、締め付けノブ６で皮膚１を固定した。
３．レセプターセル２にはディートを含まない生理食塩水９を５０ｍＬ満たした。
４．実験の間、レセプターセル２はスターラー３でセル内の生理食塩水を撹拌させ、レセプターセル２を覆っているウォータージャケット４には、ヒーター／サーキュレーター５により、３７℃の温水を循環させることで、レセプターセル２内の温度を３７℃で一定に保った。
５．レセプターセル２内の温度が３７℃になった時点から、０．５、１時間後に、レセプターセル２のサンプリング・ポート７より生理食塩水９を３ｍＬサンプリングし、その後同量のディートを含まない生理食塩水を戻し、液量を一定にした。
６．サンプリング液中のディート量をＨＰＬＣによって測定した。ディート量の測定結果より、下記式により、皮膚上残存量、皮膚上残存率を算出した。
　０．５時間後の皮膚上残存量（ｍｇ／ｃｍ２）＝（処理ディート量－０．５時間後にサンプリングした液のディート量×５０／３）／処理面積
　１時間後の皮膚上残存量（ｍｇ／ｃｍ２）＝（処理ディート量－１時間後にサンプリングした液のディート量×５０／３－０．５時間後にサンプリングした液のディート量）／処理面積
　皮膚上残存率（％）＝各時間の皮膚上残存量／処理ディート量×１００
　皮膚上残存量（ｍｇ／ｃｍ２）は小数第三位を四捨五入した数値とし、皮膚上残存率（％）は小数第一位を四捨五入した数値とした。
　試験例１－１の結果を表２（皮膚上残存量（ｍｇ／ｃｍ２））および表３（皮膚上残存率（％））に示す。 (Test method)
The test was conducted according to the following procedure. In addition, the horizontal type | mold diffusion cell (The product made from a beadrex company, the horizontal-type palm cell for flat membranes) shown in FIG. 1 was used as a test apparatus.
1. Mouse skin 1 (lab skin, obtained from Hoshino Experimental Animal Breeding Co., Ltd.) was attached to the horizontal diffusion cell 10 so that the dermis side of the skin 1 was positioned on the receptor cell 2 side.
2. About 45 μL of the prepared insect repellent composition was treated on the horny layer side (4.9 cm 2 ) of the skin 1, covered with aluminum foil 8, and the skin 1 was fixed with the tightening knob 6.
3. Receptor cell 2 was filled with 50 mL of saline 9 containing no diet.
4). During the experiment, the receptor cell 2 stirs the physiological saline in the cell with the stirrer 3, and the heater / circulator 5 circulates hot water at 37 ° C. in the water jacket 4 covering the receptor cell 2, The temperature in the receptor cell 2 was kept constant at 37 ° C.
5. Sampling 3 mL of physiological saline 9 from the sampling port 7 of the receptor cell 2 0.5 hour and 1 hour after the temperature in the receptor cell 2 reached 37 ° C. The saline solution was returned to make the liquid volume constant.
6). The amount of diet in the sampling solution was measured by HPLC. From the measurement result of the diet amount, the residual amount on the skin and the residual rate on the skin were calculated by the following formula.
Residual amount on the skin after 0.5 hours (mg / cm 2 ) = (Amount of treated diet−Amount of liquid sampled after 0.5 hours × 50/3) / Area treated on the skin after 1 hour ( mg / cm 2 ) = (deet amount of the liquid sampled after 1 hour × deeto amount of the liquid sampled after 50 hours × 50 / 3−deeto amount of the liquid sampled after 0.5 hours) / treated area remaining rate on skin (%) = each time Remaining amount of skin / processed diet amount x 100
The residual amount on the skin (mg / cm 2 ) was a value obtained by rounding off the third decimal place, and the residual rate (%) on the skin was obtained by rounding off the first decimal place.
The results of Test Example 1-1 are shown in Table 2 (residual amount on skin (mg / cm 2 )) and Table 3 (residual rate on skin (%)).
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
　表２、３に示すように、ディート単独で使用した比較例１に比べ、ディートと、ポリエチレングリコール又はポリプロピレングリコールを併用して使用した実施例１～３の方が、一定時間経過後の皮膚上のディートの残存量および残存率が、顕著に多いまたは高い結果となった。
　この結果により、ディート等の害虫忌避剤を単独で皮膚に適用するよりも、ポリエチレングリコールやポリプロピレングリコール等のポリアルキレングリコールと合わせて害虫忌避剤を皮膚に適用することにより、害虫忌避剤がより長い時間皮膚上に残存することがわかった。 As shown in Tables 2 and 3, in comparison with Comparative Example 1 in which Dieto was used alone, Examples 1 to 3 in which Diete was used in combination with polyethylene glycol or polypropylene glycol were used on the skin after a certain period of time. As a result, the amount and the residual rate of diet were significantly increased or increased.
This result shows that the pest repellent is longer when the pest repellent is applied to the skin in combination with polyalkylene glycols such as polyethylene glycol and polypropylene glycol than the pest repellent such as diet is applied alone to the skin. It was found to remain on the skin for hours.
＜試験例１－２（実施例４～８、比較例１）＞
　下記表４に示す処方に従い、害虫忌避剤組成物を調製し（実施例４～８、比較例１）、試験例１－１と同様に皮膚吸収抑制試験を行った。表４中、ＰＰ２０００（ニューポールＰＰ－２０００）は、三洋化成工業株式会社から入手したものを用いた。
　試験例１－２の結果を表５（皮膚上残存量（ｍｇ／ｃｍ２））および表６（皮膚上残存率（％））に示す。 <Test Example 1-2 (Examples 4 to 8, Comparative Example 1)>
A pest repellent composition was prepared according to the formulation shown in Table 4 below (Examples 4 to 8, Comparative Example 1), and a skin absorption inhibition test was conducted in the same manner as in Test Example 1-1. In Table 4, PP2000 (New Pole PP-2000) obtained from Sanyo Chemical Industries, Ltd. was used.
The results of Test Example 1-2 are shown in Table 5 (residual amount on skin (mg / cm 2 )) and Table 6 (residual rate on skin (%)).
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000006
　実施例４～８と試験例１－１の比較例１を比較してわかるように、ディートに対しポリプロピレングリコールを併用することにより、一定時間の経過後の皮膚上のディートの残存量および残存率が多くなるまたは高くなる結果となった。また、ポリプロピレングリコールの含有量を増やすと、濃度依存的にディートの残存量および残存率が多くなるまたは高くなる結果となった。
　また、ディートの含有量に対してポリプロピングリコールの含有量が最も少ない（ディートの含有量を１としたときのポリプロピングリコールの含有量が質量比で０．０５である）実施例４の害虫忌避組成物においても、ポリプロピングリコールを含有しない試験例１－１の比較例１の害虫忌避組成物と比較して、一定時間の経過後の皮膚上の害虫忌避剤の残存量および残存率が多いまたは高い結果となった。 As can be seen from a comparison between Examples 4 to 8 and Comparative Example 1 of Test Example 1-1, the combined use of polypropylene glycol with diet results in the residual amount and residual rate of diet after a certain period of time. Resulted in more or more. Further, when the content of polypropylene glycol was increased, the residual amount and residual rate of the diet increased or increased depending on the concentration.
Further, the pest of Example 4 having the lowest polypropyne glycol content relative to the deet content (the polypropyne glycol content is 0.05 by mass when the deet content is 1). Also in the repellent composition, compared with the pest repellent composition of Comparative Example 1 of Test Example 1-1 which does not contain polypropyne glycol, the remaining amount and the remaining rate of the pest repellent on the skin after a certain time has passed. There were many or high results.
＜試験例１－３（実施例９、比較例２）＞
　下記表７に示す処方に従い、害虫忌避剤組成物を調製し（実施例９、比較例２）、試験例１－１と同様に皮膚吸収抑制試験を行った。表７中、ＰＰ２０００（ニューポールＰＰ－２０００）は、三洋化成工業株式会社から入手したものを用いた。
　試験例１－３の結果を表８（皮膚上残存量（ｍｇ／ｃｍ２））および表９（皮膚上残存率（％））に示す。 <Test Example 1-3 (Example 9, Comparative Example 2)>
A pest repellent composition was prepared according to the formulation shown in Table 7 below (Example 9, Comparative Example 2), and a skin absorption inhibition test was conducted in the same manner as in Test Example 1-1. In Table 7, PP2000 (New Pole PP-2000) obtained from Sanyo Chemical Industries, Ltd. was used.
The results of Test Example 1-3 are shown in Table 8 (residual amount on skin (mg / cm 2 )) and Table 9 (residual rate on skin (%)).
Figure JPOXMLDOC01-appb-T000007
Figure JPOXMLDOC01-appb-T000007
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000009
Figure JPOXMLDOC01-appb-T000009
　実施例９と比較例２を比較してわかるように、ディートに対しポリプロピレングリコールを併用することにより、一定時間の経過後の皮膚上のディートの残存量および残存率が多くなるまたは高くなる結果となった。 As can be seen from a comparison between Example 9 and Comparative Example 2, when polypropylene glycol is used in combination with diet, the amount and rate of residual diet on the skin after a certain period of time increase or increase. became.
＜試験例１－４（実施例１０～１１、比較例３～４）＞
　下記表１０に示す処方に従い、害虫忌避剤組成物を調製し（実施例１０～１１、比較例３～４）、試験例１－１と同様に皮膚吸収抑制試験を行った。
　なお、メントールのｌｏｇＰ値は３．４、ｐ－メンタン３，８－ジオールのｌｏｇＰ値は１．４である。
　試験例１－３の結果を表１１（皮膚上残存量（ｍｇ／ｃｍ２））および表１２（皮膚上残存率（％））に示す。 <Test Example 1-4 (Examples 10 to 11, Comparative Examples 3 to 4)>
A pest repellent composition was prepared according to the formulation shown in Table 10 below (Examples 10 to 11 and Comparative Examples 3 to 4), and a skin absorption inhibition test was conducted in the same manner as in Test Example 1-1.
The log P value of menthol is 3.4, and the log P value of p-menthane 3,8-diol is 1.4.
The results of Test Example 1-3 are shown in Table 11 (residual amount on skin (mg / cm 2 )) and Table 12 (residual rate on skin (%)).
Figure JPOXMLDOC01-appb-T000010
Figure JPOXMLDOC01-appb-T000010
Figure JPOXMLDOC01-appb-T000011
Figure JPOXMLDOC01-appb-T000011
Figure JPOXMLDOC01-appb-T000012
Figure JPOXMLDOC01-appb-T000012
　表１１、１２に示すように、試験例１－１で使用したディートの代わりに害虫忌避剤のメントールを使用した場合であっても、害虫忌避剤を単独で使用した比較例３に比べ、害虫忌避剤とポリプロピレングリコールを併用して使用した実施例１０の方が、一定時間の経過後の皮膚上の害虫忌避剤の残存量および残存率が多いまたは高い結果となった。害虫忌避剤としてｐ‐メンタン３，８－ジオールを使用した場合も同様であった。
　この結果により、ディートの代わりに害虫忌避剤のメントールまたはｐ‐メンタン３，８－ジオールを使用した場合であっても、これら害虫忌避剤を単独で皮膚に適用するよりも、ポリプロピレングリコール等のポリアルキレングリコールと合わせて害虫忌避剤を皮膚に適用することにより、害虫忌避剤がより長い時間、皮膚上に残存することがわかった。 As shown in Tables 11 and 12, even when the insect repellent menthol was used instead of the diet used in Test Example 1-1, the insect pest was compared with Comparative Example 3 in which the insect repellent was used alone. Example 10 using a repellent and polypropylene glycol in combination resulted in a higher or higher residual amount and rate of pest repellent on the skin after a certain period of time. The same was true when p-menthane 3,8-diol was used as a pest repellent.
This result shows that even when the insect repellent menthol or p-menthane 3,8-diol is used instead of diet, these insect repellents can be used in the presence of a polymer such as polypropylene glycol rather than being applied to the skin alone. It was found that by applying a pest repellent to the skin in combination with alkylene glycol, the pest repellent remains on the skin for a longer time.
＜試験例１－５（参考例１～４）＞
　下記表１３に示す処方に従い、害虫忌避剤組成物を調製し（参考例１～４）、試験例１－１と同様に皮膚吸収抑制試験を行った。
　なお、イミダクロプリドのｌｏｇＰ値は０．８、アセタミプリドのｌｏｇＰ値は０．６である。
　試験例１－５の結果を表１４（皮膚上残存量（ｍｇ／ｃｍ２））および表１５（皮膚上残存率（％））に示す。 <Test Example 1-5 (Reference Examples 1 to 4)>
A pest repellent composition was prepared according to the formulation shown in Table 13 below (Reference Examples 1 to 4), and a skin absorption inhibition test was conducted in the same manner as in Test Example 1-1.
The log P value of imidacloprid is 0.8, and the log P value of acetamiprid is 0.6.
The results of Test Example 1-5 are shown in Table 14 (residual amount on skin (mg / cm 2 )) and Table 15 (residual rate on skin (%)).
Figure JPOXMLDOC01-appb-T000013
Figure JPOXMLDOC01-appb-T000013
Figure JPOXMLDOC01-appb-T000014
Figure JPOXMLDOC01-appb-T000014
Figure JPOXMLDOC01-appb-T000015
Figure JPOXMLDOC01-appb-T000015
　参考例１～４の害虫忌避剤組成物における害虫忌避剤（イミダクロプリド及びアセタミプリド）はｌｏｇＰ値が１未満であり、皮膚に浸透しにくい性質を有するため、ポリアルキレングリコールを併用したとしても、一定時間の経過後の皮膚上の害虫忌避剤の残存量および残存率に変化は見られなかった。 The pest repellents (imidacloprid and acetamiprid) in the pest repellent compositions of Reference Examples 1 to 4 have a log P value of less than 1 and are difficult to penetrate the skin. There was no change in the residual amount and rate of pest repellent on the skin after the passage of.
＜＜試験例２（吸血阻止試験）＞＞
＜試験例２－１（実施例１２～１４、比較例５）＞
（害虫忌避組成物の調製）
　下記表１６に示す処方に従い、各成分を撹拌下で混合して、害虫忌避組成物を調製した（実施例１２～１４、比較例５）。なお、実施例１２は試験例１－２の実施例６と、比較例５は試験例１－１の比較例１と同様の処方である。 << Test Example 2 (Blood Sucking Prevention Test) >>
<Test Example 2-1 (Examples 12 to 14, Comparative Example 5)>
(Preparation of pest repellent composition)
According to the formulation shown in Table 16 below, each component was mixed with stirring to prepare a pest repellent composition (Examples 12 to 14, Comparative Example 5). Example 12 has the same formulation as Example 6 in Test Example 1-2, and Comparative Example 5 has the same formulation as Comparative Example 1 in Test Example 1-1.
Figure JPOXMLDOC01-appb-T000016
Figure JPOXMLDOC01-appb-T000016
（試験方法）
　以下の手順により試験を行った。
１．ヘアレスマウス（オス、２０～４０ｇ）１頭にコントロール区はエタノールを、処理区は表１６に示す各害虫忌避組成物を全身に塗布し（０．５ｍＬ処理）、金網ゲージ内に動けないように固定した。
２．マウスを固定したゲージを試験ボックス内（３０ｃｍ×３０ｃｍ×３０ｃｍ）に吊るした後、ケージ内にヒトスジシマカの雌を約４０頭放した。
３．ケージ内にヒトスジシマカを放して５分後に、ケージ内からマウスを取り出した後、４０～１００℃の恒温器にケージを１分程度入れ、ケージ内のヒトスジシマカを不動状態にし、放したヒトスジシマカ全てをつぶし、吸血頭数を計測し、下記の式より、吸血率および吸血阻止率を算出した。
　吸血率（％）＝（吸血数／供試虫数）×１００
　吸血阻止率（％）＝｛（コントロール区の吸血率－処理区の吸血率）／コントロール区の吸血率｝×１００
　吸血率（％）は小数第一位を四捨五入した数値とした。
４．上記２～３を繰り返し、１時間ごとに吸血阻止率を算出した。
　試験例２－１の結果を表１７に示す。 (Test method)
The test was conducted according to the following procedure.
1. Apply one piece of hairless mouse (male, 20-40 g) to the control group with ethanol, and the treated group with the insect pest repellent composition shown in Table 16 (0.5 mL treatment) to prevent movement into the wire mesh gauge. Fixed.
2. After suspending the gauge to which the mouse was fixed in the test box (30 cm × 30 cm × 30 cm), about 40 female female females were released into the cage.
3. 5 minutes after releasing the Aedes albopictus into the cage, after removing the mouse from the cage, place the cage in a 40-100 ° C incubator for about 1 min, immobilize the Aedes albopictus in the cage, and crush all released Aedes albopictus The number of blood sucking heads was measured, and the blood sucking rate and the blood sucking inhibition rate were calculated from the following formulas.
Blood absorption rate (%) = (number of blood sucked / number of test insects) × 100
Blood absorption inhibition rate (%) = {(blood absorption rate in control group−blood absorption rate in treatment group) / blood absorption rate in control group} × 100
The blood absorption rate (%) was rounded off to the first decimal place.
4). Steps 2 to 3 were repeated, and the blood absorption inhibition rate was calculated every hour.
The results of Test Example 2-1 are shown in Table 17.
Figure JPOXMLDOC01-appb-T000017
Figure JPOXMLDOC01-appb-T000017
　表１７に示したように、ディート単独で使用した比較例５に比べ、ディートとポリエチレングリコールまたはポリプロピレングリコールを併用して使用した実施例１２～１４の方が、ディートの量が同じであるにもかかわらず、一定時間吸血阻止率が顕著に高いことが分かった。この結果により、ディート等の害虫忌避剤を単独で皮膚に適用するよりも、ポリエチレングリコール、ポリプロピレングリコール等のポリアルキレングリコールと合わせて害虫忌避剤を皮膚に適用することにより、害虫忌避剤の害虫忌避効果の持続性が向上することが分かった。 As shown in Table 17, Examples 12 to 14 in which Diete and polyethylene glycol or polypropylene glycol are used in combination have the same amount of Diet compared to Comparative Example 5 in which Diete is used alone. Regardless, it was found that the blood sucking inhibition rate was significantly high for a certain period of time. As a result, the insect repellent of the insect repellent can be obtained by applying the insect repellent to the skin in combination with the polyalkylene glycol such as polyethylene glycol or polypropylene glycol, rather than applying the insect repellent such as diet alone to the skin. It was found that the sustainability of the effect was improved.
＜試験例２－２（実施例１５～１６、比較例６）＞
　下記表１８に示す処方に従い、害虫忌避剤組成物を調製し（実施例１５～１６、比較例６）、試験例２－１と同様の手順により試験を行った。
　試験例２－２の結果を表１９に示す。 <Test Example 2-2 (Examples 15 to 16, Comparative Example 6)>
According to the formulation shown in Table 18 below, pest repellent compositions were prepared (Examples 15 to 16, Comparative Example 6) and tested according to the same procedure as in Test Example 2-1.
The results of Test Example 2-2 are shown in Table 19.
Figure JPOXMLDOC01-appb-T000018
Figure JPOXMLDOC01-appb-T000018
Figure JPOXMLDOC01-appb-T000019
Figure JPOXMLDOC01-appb-T000019
　実施例１５、１６において、比較例６に対してディートの量を３／５に減らしたにも関わらず、ディートと、ポリエチレングリコールまたはポリプロピレングリコールを併用して使用することによって、一定時間の吸血阻止率が高くなることが分かった。
　この結果により、ディート等の害虫忌避剤を単独で皮膚に適用するよりも、ポリエチレングリコール、ポリプロピレングリコール等のポリアルキレングリコールと合わせて害虫忌避剤を皮膚に適用することにより、皮膚における害虫忌避剤の害虫忌避効果の持続性が向上することがわかった。 In Examples 15 and 16, even though the amount of diet was reduced to 3/5 compared to Comparative Example 6, it was possible to prevent blood sucking for a certain period of time by using both diet and polyethylene glycol or polypropylene glycol in combination. It turns out that the rate is high.
As a result of this, by applying a pest repellent to the skin in combination with a polyalkylene glycol such as polyethylene glycol or polypropylene glycol, rather than applying a pest repellent such as diet alone to the skin, It was found that the sustainability of the pest repellent effect was improved.
＜＜試験例３（皮膚刺激抑制試験）＞＞
　本試験では被験者１０名（男性５人、女性５人；Ｎｏ．１～１０）の皮膚に本発明の害虫忌避組成物を適用し、害虫忌避剤の皮膚に対する刺激が抑制されるかについて試験を行った。
（害虫忌避組成物の調製）
［実施例１７～１９、比較例７］
　下記表２０～２３に示す処方に従い、各成分を撹拌下で混合して、実施例１７～１９、比較例７の害虫忌避組成物を調製した。 << Test Example 3 (Skin Irritation Inhibition Test) >>
In this test, the pest repellent composition of the present invention was applied to the skin of 10 subjects (5 men, 5 women; No. 1 to 10) to test whether the irritation to the skin of the pest repellent was suppressed. went.
(Preparation of pest repellent composition)
[Examples 17 to 19, Comparative Example 7]
According to the formulations shown in Tables 20 to 23 below, the components were mixed with stirring to prepare the pest repellent compositions of Examples 17 to 19 and Comparative Example 7.
Figure JPOXMLDOC01-appb-T000020
Figure JPOXMLDOC01-appb-T000020
Figure JPOXMLDOC01-appb-T000021
Figure JPOXMLDOC01-appb-T000021
Figure JPOXMLDOC01-appb-T000022
Figure JPOXMLDOC01-appb-T000022
Figure JPOXMLDOC01-appb-T000023
Figure JPOXMLDOC01-appb-T000023
　なお、表２０～２３において、グリセリン脂肪酸エステルは、モノオレイン酸デカグリセリル（デカグリン１－ＯＶ；日光ケミカルズ社より入手）を用いた。 In Tables 20 to 23, decaglyceryl monooleate (decagulin 1-OV; available from Nikko Chemicals) was used as the glycerin fatty acid ester.
（観察・検査項目および判定）
　本試験は、（１）事前検診、（２）被験薬貼付、（３）被験薬除去、（４）自覚症状の質問、（５）皮膚反応の観察・判定を以下の表２４に示すスケジュールで行った。 (Observation / inspection items and judgment)
This study consists of (1) prior screening, (2) test drug application, (3) test drug removal, (4) subjective symptom questions, and (5) skin reaction observation / determination according to the schedule shown in Table 24 below. went.
Figure JPOXMLDOC01-appb-T000024
Figure JPOXMLDOC01-appb-T000024
（１）事前検診
　試験開始直前に被験者に自覚症状（薬剤アレルギー、痛み、痒み等）について質問し、試験への参加の適否を判断した。
（２）被験薬貼付
　上記調整した各被験薬（実施例１７～１９、及び比較例７の害虫忌避組成物）と、対照薬（精製水）を皮膚テスト用パッチテープ（リバテープ製薬社製）のパッドに約０．０３ｍＬ滴下し、各被験者の両上腕内側部に貼付した。なお、各被験薬の濃度は等倍に設定した。
（３）被験薬除去
　被験薬を貼付してから２４時間後に被験薬を除去した。
（４）自覚症状の質問
　被験薬貼付直後、被験薬貼付２４時間後、被験薬除去１時間後に被験者に痛みや痒みの有無についての質問を行い、自覚症状を確認した。
（５）皮膚反応の観察・判定
　皮膚反応の出やすい被験薬除去１時間後に対照薬（精製水）貼付部位の皮膚反応を対照として、被験薬貼付部位の皮膚反応を観察し、判定した。判定は以下のＩＣＤＲＧ（国際接触皮膚炎研究会）基準に従い行った。
［ＩＣＤＲＧ基準］
　－：全く無反応
　±：かすかな紅斑のみ
　１＋：弱い（小水疱なし）陽性反応、軽度紅斑、丘疹
　２＋：強い（小水疱あり）陽性反応、明らかな紅斑、丘疹
　３＋：非常に強い陽性反応、強度紅斑、腫脹、大水疱 (1) Prior screening Immediately before the start of the study, subjects were asked about subjective symptoms (drug allergies, pain, itching, etc.), and the suitability of participation in the study was judged.
(2) Test drug sticking Each of the prepared test drugs (pest repellent compositions of Examples 17 to 19 and Comparative Example 7) and a control drug (purified water) were applied to a skin test patch tape (manufactured by Riba Tape Pharmaceutical Co., Ltd.). About 0.03 mL was dropped onto the pad and attached to the inner side of both upper arms of each subject. In addition, the density | concentration of each test drug was set to 1 time.
(3) Test drug removal The test drug was removed 24 hours after applying the test drug.
(4) Question about subjective symptoms Immediately after application of the test drug, 24 hours after application of the test drug, and 1 hour after removal of the test drug, the subject was asked about the presence or absence of pain or itch, and the subjective symptoms were confirmed.
(5) Observation / determination of skin reaction One hour after removal of the test drug, which is likely to cause a skin reaction, the skin reaction at the site where the control drug (purified water) was applied was used as a control to observe and determine the skin reaction at the site where the test drug was applied. The determination was made according to the following ICDRG (International Contact Dermatitis Research Association) standard.
[ICDRG standards]
-: No reaction at all ±: Only faint erythema 1+: Weak (no blister) positive reaction, mild erythema, papule 2+: Strong (with blister) positive reaction, clear erythema, papule 3+: Very strong positive reaction, Intense erythema, swelling, large blisters
　また、各種判定結果に評価点（－：０点、±：０．５点、１＋：１点、２＋：２点、３＋：３点）を与え、平均評価点を算出した。結果を表２５に示す。 In addition, evaluation points (−: 0 point, ±: 0.5 point, 1+: 1 point, 2+: 2 point, 3+: 3 point) were given to various determination results, and an average evaluation point was calculated. The results are shown in Table 25.
Figure JPOXMLDOC01-appb-T000025
Figure JPOXMLDOC01-appb-T000025
　実施例１７～１９のポリプロピレングリコールを含有する害虫忌避組成物を２４時間貼付した結果、除去１時間後に１名の被験者（Ｎｏ．６）においてかすかな紅斑（評価±）が認められたものの、他の被験者において皮膚反応は全く見られなかった。平均評価点に関しても、いずれも０．０５点と低い点数であった。また、各判定時の自覚症状の質問においても、痛みや痒みの自覚症状を訴える被験者はいなかった。 As a result of applying the pest repellent composition containing polypropylene glycol of Examples 17 to 19 for 24 hours, a slight erythema (evaluation ±) was observed in one subject (No. 6) 1 hour after removal, No skin reaction was seen in any of the subjects. All of the average evaluation points were as low as 0.05 points. In addition, no subject complained of subjective symptoms of pain or itch in the subjective symptom questions at each determination.
　一方、比較例７のポリプロピレングリコールを含有しない害虫忌避組成物を２４時間貼付した結果、除去１時間後に９名もの被験者においてかすかな紅斑（評価±）が認められた。平均評価点も０．４５点となり、実施例と比較して評価点が高くなる結果となった。 On the other hand, as a result of applying the pest repellent composition containing no polypropylene glycol of Comparative Example 7 for 24 hours, faint erythema (evaluation ±) was observed in 9 subjects 1 hour after removal. The average evaluation score was also 0.45, and the evaluation score was higher than that of the example.
　以上の結果より、ポリプロピレングリコールを含有する害虫忌避組成物は、ポリプロピレングリコールを含有しない場合と比較して、皮膚に対する刺激が抑制されていることがわかった。したがって、ポリアルキレングリコールを害虫忌避剤とともに皮膚に適用することにより、害虫忌避剤の皮膚に対する刺激を抑制できることがわかった。 From the above results, it was found that the pest repellent composition containing polypropylene glycol is less irritating to the skin than the case of not containing polypropylene glycol. Therefore, it was found that the irritation to the skin of the pest repellent can be suppressed by applying polyalkylene glycol to the skin together with the pest repellent.
　本発明を特定の態様を用いて詳細に説明したが、本発明の意図と範囲を離れることなく様々な変更及び変形が可能であることは、当業者にとって明らかである。なお本出願は、２０１５年２月１７日付で出願された日本特許出願（特願２０１５－０２８６４８）に基づいており、その全体が引用により援用される。 Although the present invention has been described in detail using specific embodiments, it will be apparent to those skilled in the art that various modifications and variations can be made without departing from the spirit and scope of the invention. Note that this application is based on a Japanese patent application filed on Feb. 17, 2015 (Japanese Patent Application No. 2015-028648), which is incorporated by reference in its entirety.
１．皮膚
２．レセプターセル
３．スターラー
４．ウォータージャケット
５．ヒーター／サーキュレーター
６．締め付けノブ
７．サンプリング・ポート
８．アルミ箔
９．生理食塩水
１０．水平型拡散セル 1. Skin 2. 2. receptor cell Stirrer 4. 4. Water jacket Heater / circulator 6. Tightening knob Sampling port 8. Aluminum foil9. Physiological saline 10. Horizontal diffusion cell

Claims (6)

  1. 　ポリアルキレングリコールを害虫忌避剤とともに皮膚に適用することにより、害虫忌避剤の皮膚への浸透を抑制する方法。 A method of suppressing penetration of a pest repellent into the skin by applying polyalkylene glycol to the skin together with the pest repellent.
  2. 　前記害虫忌避剤のｌｏｇＰ値が１以上である、請求項１に記載の方法。 The method according to claim 1, wherein the pest repellent has a log P value of 1 or more.
  3. 　前記ポリアルキレングリコールの分子量が２００～２００００である請求項１または２に記載の方法。 The method according to claim 1 or 2, wherein the polyalkylene glycol has a molecular weight of 200 to 20,000.
  4. 　前記ポリアルキレングリコールが、ポリプロピレングリコールである、請求項１～３のいずれか１項に記載の方法。 The method according to any one of claims 1 to 3, wherein the polyalkylene glycol is polypropylene glycol.
  5. 　ポリアルキレングリコールを含有する、害虫忌避剤の皮膚への浸透抑制剤。 Pest repellent penetration inhibitor containing polyalkylene glycol.
  6. 　ポリアルキレングリコールの、皮膚上に適用した害虫忌避剤の皮膚への浸透を抑制させるための使用。 Use of polyalkylene glycol to suppress penetration of pest repellent applied on the skin into the skin.
PCT/JP2016/054582 2015-02-17 2016-02-17 Method for inhibiting penetration of insect pest repellant into skin and agent for inhibiting penetration of insect pest repellant into skin WO2016133124A1 (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021147334A (en) * 2020-03-17 2021-09-27 日油株式会社 Percutaneous absorption inhibitor and pest repellent composition

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59222402A (en) * 1983-06-02 1984-12-14 Otsuka Kagu Kogyo Kk Insecticide composition
JPH04244001A (en) * 1990-06-18 1992-09-01 Taisho Pharmaceut Co Ltd Composition for repelling insect pest
JP2003171204A (en) * 2001-12-04 2003-06-17 Kowa Co Gel-like insect repellent formulation
JP2003171205A (en) * 2001-12-04 2003-06-17 Kowa Co Gel-like insect repellent formulation
JP2009126804A (en) * 2007-11-21 2009-06-11 Dainippon Jochugiku Co Ltd Noxious insect repellent for human body

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6670313B1 (en) * 2000-06-05 2003-12-30 Colormetric Laboratories, Inc. Method and composition for minimizing percutaneous absorption of industrial chemicals

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS59222402A (en) * 1983-06-02 1984-12-14 Otsuka Kagu Kogyo Kk Insecticide composition
JPH04244001A (en) * 1990-06-18 1992-09-01 Taisho Pharmaceut Co Ltd Composition for repelling insect pest
JP2003171204A (en) * 2001-12-04 2003-06-17 Kowa Co Gel-like insect repellent formulation
JP2003171205A (en) * 2001-12-04 2003-06-17 Kowa Co Gel-like insect repellent formulation
JP2009126804A (en) * 2007-11-21 2009-06-11 Dainippon Jochugiku Co Ltd Noxious insect repellent for human body

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
QIU, HONGCHUN ET AL.: "Formulation of topical insect repellent N,N-diethyl-m-toluamide (DEET): vehicle effects on DEET in vitro skin permeation", INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 163, no. 1-2, 1998, pages 167 - 176, ISSN: 0378-5173 *
ROSS, J. S. ET AL.: "Reduction in skin permeation of N,N-diethyl-m-toluamide (DEET) by altering the skin/vehicle partition coefficient", JOURNAL OF CONTROLLED RELEASE, vol. 67, no. 2-3, 2000, pages 211 - 221, ISSN: 0168-3659 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2021147334A (en) * 2020-03-17 2021-09-27 日油株式会社 Percutaneous absorption inhibitor and pest repellent composition
JP7344451B2 (en) 2020-03-17 2023-09-14 日油株式会社 Transdermal absorption inhibitor and insect repellent composition

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