Metered dose spray type aerosol, method for spraying metered dose spray type aerosol, and method for improving sustainability of effect of drug

Abstract

An object of the present invention is to provide a metered-dose spray type aerosol which enhances the sustainability of a drug and improves the efficacy.SOLUTION: The metered spray type aerosol of the present invention is a metered spray type aerosol that sprays a constant amount of an aerosol composition by a single spray operation, wherein the aerosol composition comprises a stock solution containing a drug and a propellant, and is filled in a pressure vessel, and the metered spray type aerosol has a single spray amount of 1.0 to 3. 0mL and a single spray time of 0.8 seconds or less.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a metered dose aerosol, a spraying method using the same, and a method for improving the efficacy of a drug ejected when the metered dose aerosol is sprayed. [Background technology]

[0002] Metered-dose aerosols are known that spray a fixed amount of an aerosol composition consisting of a concentrate containing a drug as an active ingredient and a propellant in a single spray operation. Because metered-dose aerosols eject a predetermined amount of drug in a single spray operation, there is little variation in the operation method between users (such as differences in the amount sprayed due to the method of pressing the spray button or the duration of pressing), and this has the advantage of less variation in effectiveness.

[0003] As an example of such a metered dose aerosol, Patent Document 1 discloses an aerosol for pest control equipped with an aerosol valve for metered spray with a spray volume of 0.35 to 0.9 mL per spray. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Publication No. 2010-280633 Summary of the Invention [Problem to be solved by the invention]

[0005] As mentioned above, metered-dose aerosols for use in the air, such as insecticide aerosols and air freshener aerosols, have the advantage of little variation in effectiveness, but if the amount sprayed per time is small, the user does not feel fully satisfied with the product, and even though an effective amount of the product is discharged in one spray, multiple sprays can result in excessive consumption. Furthermore, conventional metered-dose aerosols have a limit to how long the product lasts, and in order to maintain this effect, the spraying operation must be repeated after a certain time has passed since the spray, which requires frequent repetition. Therefore, an object of the present invention is to improve the efficacy of medicines and to provide a metered dose aerosol that improves the efficacy of medicines, increases the duration of their effects, and provides a real feeling of use. [Means for solving the problem]

[0006] As a result of extensive research, the inventors have found that if a metered dose aerosol capable of spraying large volumes of 1.0 mL or more is developed, the amount sprayed per spray operation will be large, thereby improving the feel of use while also increasing the amount of medicine ejected; further, they have found that with a metered dose aerosol that sprays large volumes, the duration of the medicine's effect will vary depending on the spray duration per spray operation, and that there is an optimal balance between the amount of aerosol composition sprayed per spray operation and the spray duration for sustaining the medicine's effect.

[0007] That is, the present invention is characterized by the following (1) to (8). (1) A metered-dose aerosol that sprays a fixed amount of aerosol composition with one spray operation, said aerosol composition consisting of a concentrate containing a drug and a propellant, and filled in a pressure-resistant container, said metered-dose aerosol having a single spray volume of 1.0 to 3.0 mL and a single spray time of 0.8 seconds or less. (2) The metered dose aerosol according to (1) above, wherein the duration of each spray is 0.20 to 0.75 seconds. (3) A metered dose aerosol according to (1) or (2), wherein the concentrate further contains a solvent. (4) The metered dose aerosol according to any one of (1) to (3) above, wherein the content of the drug in the concentrate is 0.01 to 70% by mass / volume. (5) The metered dose aerosol according to any one of (1) to (4) above, wherein the volume ratio of the concentrate to the propellant in the aerosol composition is 1:99 to 50:50. (6) The metered dose aerosol according to any one of (1) to (5), wherein the agent is at least one selected from the group consisting of pest control components, fragrance components, deodorizing components, and disinfecting / bactericidal components. (7) A method for spraying a metered dose aerosol, in which a pressure-resistant container is filled with an aerosol composition consisting of a concentrate containing a drug and a propellant, and the amount sprayed in one spray operation is 1.0 to 3.0 mL and the spray time is 0.8 seconds or less. (8) A method for improving the efficacy of a drug in an aerosol composition sprayed using a metered dose aerosol, comprising spraying a fixed amount of the aerosol composition in the range of 1.0 to 3.0 mL within 0.8 seconds. [Effects of the Invention]

[0008] According to the metered dose aerosol of the present invention, the aerosol composition can be sprayed in a large amount in a predetermined amount in the range of 1.0 to 3.0 mL in a single spray operation, thereby improving the efficacy of the drug. Furthermore, the duration of the efficacy of the drug in the aerosol composition can be increased. Therefore, there is no difference in the operation method depending on the user, so there is no variation in the effect, and wasteful overuse can be avoided. In addition, the efficacy of the drug can be improved and the effect of the drug can be sustained in a single spray operation. [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 is a plan view for explaining the test chamber used in Test Example 1. As shown in FIG. [Figure 2] FIG. 2 is a perspective view for explaining the test method of Test Example 2. [Figure 3]FIG. 3 is a plan view illustrating the test chamber used in Test Example 4. DETAILED DESCRIPTION OF THE INVENTION

[0010] Hereinafter, the embodiments of the present invention will be described in more detail. In this specification, "mass" is synonymous with "weight."

[0011] The metered dose aerosol of the present invention is prepared by filling a pressure-resistant container with an aerosol composition containing a drug concentrate and a propellant. Each component will be described below.

[0012] (Undiluted) The concentrate constituting the aerosol composition of the present invention contains at least a chemical agent as an active ingredient. The active ingredient is a substance that exerts some kind of effect when a metered-dose aerosol is used, and includes, but is not limited to, pest control ingredients, fragrance ingredients, deodorizing ingredients, disinfecting and sterilizing ingredients, etc.

[0013] The pest control component is a component that can kill, repel, knock down, etc., target pests. The type of pest control component is not particularly limited, and known compounds can be used. Examples of pest control ingredients include pyrethroid compounds such as permethrin, pyrethrins, allethrin, phthalthrin, resmethrin, furamethrin, fenothrin, empenthrin, prallethrin, cyphenothrin, imiprothrin, transfluthrin, metofluthrin, dimefluthrin, and mepafluthrin; organophosphorus compounds such as fenitrothion, dichlorvos, chlorpyrifos-methyl, diazinon, and fenthion; carbaryl, Carbamate compounds such as propoxur; compounds such as methoprene, pyriproxyfen, methoxadiazone, fipronil, amidoflumet, and broflanilide; peppermint oil, orange oil, fennel oil, cinnamon oil, clove oil, turpentine oil, eucalyptus oil, cypress oil, jasmine oil, neroli oil, peppermint oil, bergamot oil, butygrain oil, lemon oil, lemongrass oil, cinnamon oil, citronella oil, geranium oil, citral, and l-menthol. Examples of essential oil components include ethanol, citronellyl acetate, cinnamic aldehyde, terpineol, nonyl alcohol, cis-jasmone, limonene, linalool, 1,8-cineole, geraniol, α-pinene, p-menthane-3,8-diol, eugenol, menthyl acetate, thymol, benzyl benzoate, and benzyl salicylate; glycol ethers such as propylene glycol monopropyl ether, propylene glycol monobutyl ether, dipropylene glycol monopropyl ether, dipropylene glycol monobutyl ether, dipropylene glycol dimethyl ether, ethylene glycol monoisobutyl ether, diethylene glycol monoisobutyl ether, diethylene glycol dibutyl ether, diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether; and dibasic acid esters such as dibutyl adipate. These may be used alone or in combination of two or more.

[0014] The pest control component may be appropriately selected depending on the type of target pest, such as mosquitoes, flies, moths, bees, stink bugs, cockroaches, ants, spiders, pill bugs, mites, lice, centipedes, caterpillars, millipedes, spiders, horseflies, black flies, moths, termites, midges, leafhoppers, bark beetles, ground beetles, earwigs, silverfish, longhorn beetles, dermestid beetles, psocids, bur moths, and wood moths. Transfluthrin, metofluthrin, profluthrin, phthalthrin, prallethrin, momfluorothrin, etc. are suitable for use against flying pests such as mosquitoes, flies, moths, wasps, horseflies, black flies, midges, leafhoppers, moths, and box moths. Phthalthrin, prallethrin, imiprothrin, permethrin, fenothrin, etc. are suitable for use against crawling pests such as cockroaches, stink bugs, ants, spiders, pill bugs, mites, lice, centipedes, caterpillars, millipedes, spiders, termites, bark beetles, ground beetles, earwigs, and silverfish.

[0015] Aromatic components are components that emit a fragrance. Examples of aromatic components include the essential oil components described above, as well as natural fragrances such as anise oil, lavender oil, rose oil, rosemary oil, and grapefruit oil; and synthetic fragrances such as camphene, p-cymene, citronellol, nerol, benzyl alcohol, n-butyraldehyde, isobutyraldehyde, coumarin, and cineole. These may be used alone or in combination of two or more.

[0016] Deodorizing components are components that can eliminate odors. Examples of deodorizing components include components that adsorb odorous components such as green tea extract, persimmon tannin, lauric acid methacrylate, methyl benzoate, methyl phenylacetate, geranyl crotrate, acetophenone myristate, benzyl acetate, benzyl propionate, and silver, as well as components that mask odorous components such as the above-mentioned aromatic components. These may be used alone or in combination of two or more.

[0017] The disinfecting / bactericidal component is a component that removes or kills microorganisms, molds, and bacteria. Examples of disinfecting / bactericidal components include ethanol, hinokitiol, 2-mercaptobenzothiazole, 2-(4-thiazolyl)benzimidazole, 5-chloro-2-methyl-4-isothiazolin-3-one, triforine, p-chlorometaxylenol, 3-methyl-4-isopropylphenol, ortho-phenylphenol, chlorhexidine gluconate, polylysine, chitosan, tetrahydrolinalool, and dialkyldimethylammonium chloride. These may be used alone or in combination of two or more.

[0018] The above-mentioned chemicals can be used in combination with components having different effects, for example, a pest control component and a fragrance component can be used in combination, or a fragrance component can be used in combination with a deodorizing component other than a fragrance component.

[0019] The content of the drug in the concentrate is preferably 0.01 to 70% by mass / volume. When the drug is present in the concentrate at 0.01% by mass / volume or more, sufficient drug effects can be obtained, and when the content is 70% by mass / volume or less, productivity is improved. The lower limit of the drug content is more preferably 0.1% by mass / volume or more, even more preferably 0.3% by mass / volume or more, and particularly preferably 0.5% by mass / volume or more, and the upper limit is more preferably 65% ​​by mass / volume or less, even more preferably 50% by mass / volume or less, and particularly preferably 25% by mass / volume or less.

[0020] The stock solution may contain a solvent for purposes such as adjusting the viscosity of the stock solution, improving production suitability, and increasing the penetration of the agent against pests. Examples of such solvents include the above-mentioned glycol ethers, hydrocarbon solvents, alcohol solvents, aromatic solvents, and ester solvents. Water and surfactants may also be used. Examples of hydrocarbon solvents include aliphatic hydrocarbons and alicyclic hydrocarbons such as paraffinic hydrocarbons and naphthenic hydrocarbons, with kerosene such as JIS No. 1 kerosene being preferred. Specific examples include normal paraffin and isoparaffin. Typical normal paraffins have a carbon number of 8 to 16, such as Neo Thiosol manufactured by Chuo Kasei Co., Ltd. and Normal Paraffin MA manufactured by JXTG Nippon Oil & Energy Corporation. Typical isoparaffins have a carbon number of 8 to 16, such as IP Clean LX and Supersol FP25 manufactured by Idemitsu Kosan Co., Ltd. Examples of alcohol-based solvents include lower alcohols such as ethanol and propanol (normal and iso), and polyhydric alcohols such as glycerin and ethylene glycol. Examples of aromatic solvents include toluene and xylene. Examples of ester solvents include isopropyl myristate, hexyl laurate, and isopropyl palmitate.

[0021] The solvent content in the concentrate is preferably 30 to 99.99% by mass / volume. Having the solvent content in the concentrate at 30% by mass / volume or more can improve productivity, while a content of 99.99% by mass / volume or less is preferred because it ensures sufficient drug efficacy. The lower limit of the solvent content is more preferably 35% by mass / volume or more, and even more preferably 50% by mass / volume or more, while the upper limit is more preferably 99.9% by mass / volume or less, and even more preferably 99.5% by mass / volume or less.

[0022] The concentrate may contain other ingredients, such as preservatives, pH adjusters, UV absorbers, inorganic substances, surfactants, and solubilizing agents, as long as the ingredients do not impair the effects of the present invention.

[0023] The content of the concentrate in the aerosol composition can be varied as appropriate depending on the intended use of the metered-dose aerosol and the combination with the propellant, and is not particularly limited. For example, it can be 1 to 50% by volume in the aerosol composition. When the concentrate is 1% by volume or more in the aerosol composition, sufficient drug efficacy can be obtained, and when it is 50% by volume or less, the concentrate can be sprayed as atomized particles, thereby reducing contamination of furniture, floors, walls, etc., when used indoors, for example. The lower limit of the concentrate content in the aerosol composition is more preferably 3% by volume or more, and even more preferably 5% by volume or more, and the upper limit is more preferably 40% by volume or less, and even more preferably 30% by volume or less.

[0024] (propellant) The propellant is a medium for spraying the concentrate, and is filled under pressure together with the concentrate into a pressure-resistant container. The propellant may be one or more of the following: liquefied petroleum gases (LPG) such as propane, propylene, n-butane, isobutane, etc.; liquefied gases such as dimethyl ether (DME); compressed gases such as carbon dioxide, nitrogen gas, and compressed air; halogenated carbon gases such as HFC-152a, HFC-134a, HFO-1234yf, HFO-1234ze, etc. The propellant to be used may be selected appropriately depending on the compatibility with the concentrate and the container components such as an aerosol valve.

[0025] The content of the propellant in the aerosol composition can be varied as appropriate depending on the intended use of the metered-dose aerosol and the combination with the concentrate, and is not particularly limited. For example, it can be 50 to 99% by volume in the aerosol composition. When the propellant content in the aerosol composition is 50% by volume or more, the concentrate can be sprayed as spray particles, making the drug more easily diffused and the drug's effect more likely to last. Furthermore, when the propellant content is 99% by volume or less, sufficient drug effect can be obtained. The propellant content in the aerosol composition is preferably 60% by volume or more at its lower limit, more preferably 70% by volume or more, and more preferably 97% by volume or less at its upper limit, more preferably 95% by volume or less.

[0026] The volume ratio of the concentrate to the propellant in the aerosol composition is preferably 1:99 to 50:50, more preferably 3:97 to 40:60, and even more preferably 5:95 to 30:70. By setting the volume ratio in this range, sufficient drug effects can be obtained.

[0027] (metered-volume aerosol) The metered dose aerosol of the present invention is constructed by filling the concentrate and propellant into a pressure-resistant aerosol container, and closing the opening of the pressure-resistant container with an aerosol valve.

[0028] A metered dose aerosol is an aerosol that sprays a fixed amount of aerosol composition with one spray operation. When a user operates a spray member (hereinafter also referred to as a spray button) attached to an aerosol valve, a fixed amount of the aerosol composition (concentrate and propellant) in a pressure-resistant container is sprayed through the aerosol valve, and the concentrate is converted into particles by the propellant and sprayed as spray particles.

[0029] (aerosol valve) The aerosol valve comprises an opening / closing member for switching communication between the inside and outside of the pressure-resistant container on and off by operating the spray member by the user, a housing to which the opening / closing member is attached, and a mounting member for holding the housing in a predetermined position on the pressure-resistant container. The opening / closing member also includes a stem that slides up and down in conjunction with the spray member. The sliding of the stem switches between communication (spray state) and blockage (non-spray state) of the aerosol composition. The aerosol valve is formed with a housing hole for taking in the aerosol composition from the pressure-resistant container and a stem hole for delivering the taken-in aerosol composition to the spray member. The housing is formed with a housing hole for taking in the aerosol composition from the pressure-resistant container. The stem is formed with a stem hole for delivering the aerosol composition taken in the housing to the spray member. The path from the housing hole to the stem hole constitutes an internal passage through which the aerosol composition passes.

[0030] In the present invention, the aerosol valve is a metered-volume aerosol valve that sprays a fixed amount with a single operation of the spray member. The spray volume of the aerosol valve is a predetermined fixed amount in the range of 1.0 to 3.0 mL per spray operation. By using an aerosol valve having a housing that can store a predetermined amount of aerosol composition in the range of 1.0 to 3.0 mL per spray operation, a predetermined fixed amount in the range of 1.0 to 3.0 mL can be sprayed with a single spray operation, making it possible to spray a large amount of medicine. The spray volume of the aerosol valve can be appropriately set within the above range.

[0031] (Injection member) The spray member (spray button) is a component attached to the pressure-resistant container via the aerosol valve. The spray button is formed with a passage in the operating part through which the aerosol composition taken in from the pressure-resistant container via the stem hole of the aerosol valve passes, and a nozzle through which the aerosol composition is sprayed.

[0032] From the viewpoint of setting the injection time within the desired range, the inner diameter of the injection button's nozzle (nozzle hole diameter) is preferably φ0.45 to 3.0 mm, more preferably φ0.5 to 2.0 mm, and even more preferably φ0.6 to 1.6 mm. It is also acceptable to have multiple nozzles with the same area.

[0033] (injection pressure) As described above, the metered dose aerosol of the present invention is prepared by filling a pressure-resistant aerosol container with a concentrate and a propellant, i.e., an aerosol composition, and then pressing the spray button to spray a fixed amount of the aerosol composition with each press. The spray pressure of the aerosol composition at a position 20 cm away from the nozzle is preferably 5 to 40 gf, more preferably 8 to 30 gf. By keeping the spray pressure within the above range, the spray time can be set within the desired range. The spray pressure can be measured by spraying the aerosol composition toward the center of a circular flat plate with a diameter of 60 mm attached to a digital force gauge (e.g., manufactured by Imada Co., Ltd., model number: DS2-2N) placed horizontally at a distance of 20 cm from the nozzle of a metered-volume aerosol under room temperature conditions of 25°C, and calculating the average of the maximum value as the spray load.

[0034] (injection time) The metered dose aerosol of the present invention has a spray time of 0.8 seconds or less per spray operation. Although the reason why the effects of the present invention are achieved is unclear, by spraying a predetermined amount of aerosol composition in the range of 1.0 to 3.0 mL per spray within 0.8 seconds, the volatility of the drug can be efficiently increased, thereby improving the efficacy of the drug. Furthermore, it is believed that this also increases the duration of the drug's effect. The injection time for one injection operation is preferably within 0.75 seconds, more preferably 0.10 to 0.75 seconds, even more preferably 0.20 to 0.75 seconds, and particularly preferably 0.25 to 0.75 seconds.

[0035] In the present invention, methods for adjusting the spray time for one spray operation include, for example, adjusting the size of the nozzle of the spray button, adjusting the spray pressure of a metered dose aerosol, adjusting the stem hole diameter of an aerosol valve, adjusting the pressure of the propellant, and combinations of these.

[0036] By using the metered dose aerosol of the present invention to spray a fixed amount of aerosol composition in the range of 1.0 to 3.0 mL within 0.8 seconds, the efficacy of the drug in the sprayed aerosol composition can be improved, thereby increasing the duration of the drug's effectiveness. [Example]

[0037] The present invention will be further explained below with reference to examples and comparative examples, but the present invention is not limited to the following examples.

[0038] <Test Example 1: Insecticidal efficacy confirmation test against Culex pipiens mosquitoes> 1. Stock Solution Preparation According to the formulation shown in Table 1, transfluthrin was measured out and isopropanol (specific gravity 0.785 (20°C)) was added to make up to 100 mL, thereby preparing stock solutions 1 to 3.

[0039] [Table 1]

[0040] 2. Preparation of metered dose aerosol According to Table 2, fixed-dose aerosols of Examples 1 to 5 and Comparative Examples 1 to 5 were prepared.

[0041] Example 1 12.8 mL of concentrate 1 was filled into an aerosol pressure can (volume 294 mL) and fitted with an aerosol valve (amount per injection: 1.0 mL, stem hole area: 1.4 mm 2 The aerosol pressure can was then sealed with a cap. 187.2 mL of liquefied petroleum gas (0.49 MPa (25°C)) was then filled under pressure as a propellant. A spray button (nozzle hole diameter φ1.6 mm) was attached to the aerosol valve, and a metered-dose aerosol was obtained with a spray volume of 1.0 mL per push and an ejection amount of 16 mg of transfluthrin.

[0042] Example 2 A metered dose aerosol with a spray volume of 1.0 mL per push and an ejection volume of 16 mg of transfluthrin was obtained in the same manner as in Example 1, except that the spray button was changed to one with an orifice diameter of φ0.6 mm.

[0043] (Comparative Example 1) A metered dose aerosol with a spray volume of 1.0 mL per push and an ejection volume of 16 mg of transfluthrin was obtained in the same manner as in Example 1, except that the spray button was changed to one with an orifice diameter of 0.4 mm.

[0044] Example 3 The aerosol valve has a single injection volume of 1.0 mL and a stem hole area of ​​0.5 mm. 2 A metered dose aerosol spray with a spray amount of 1.0 mL per push and an ejection amount of transfluthrin of 16 mg was obtained in the same manner as in Example 1, except that the above was changed to the above.

[0045] Example 4 The aerosol valve has a single injection volume of 1.0 mL and a stem hole area of ​​0.28 mm. 2 A metered dose aerosol spray with a spray amount of 1.0 mL per push and an ejection amount of transfluthrin of 16 mg was obtained in the same manner as in Example 1, except that the above was changed to the above.

[0046] (Comparative Example 2) The aerosol valve has a single injection volume of 1.0 mL and a stem hole area of ​​0.13 mm. 2 A metered dose aerosol spray with a spray amount of 1.0 mL per push and an ejection amount of transfluthrin of 16 mg was obtained in the same manner as in Example 1, except that the above was changed to the above.

[0047] Example 5 12.8 mL of concentrate 2 was filled into an aerosol pressure can (volume 294 mL) and fitted with an aerosol valve (single injection volume 2.2 mL, stem hole area 1.4 mm 2 The aerosol pressure can was then sealed with a cap. 187.2 mL of liquefied petroleum gas (0.49 MPa (25°C)) was then filled under pressure as a propellant. A spray button (nozzle hole diameter φ1.6 mm) was attached to the aerosol valve, and a metered-dose aerosol was obtained with a spray volume of 2.2 mL per push and an ejection volume of 16 mg of transfluthrin.

[0048] (Comparative Example 3) A metered dose aerosol with a spray volume of 2.2 mL per push and an ejection volume of 16 mg of transfluthrin was obtained in the same manner as in Example 5, except that the spray button was changed to one with an orifice diameter of φ0.6 mm.

[0049] Comparative Example 4 3.2 mL of concentrate 3 was filled into an aerosol pressure can (volume 59 mL) and fitted with an aerosol valve (amount per injection: 0.2 mL, stem hole area: 0.4 mm 2 The aerosol pressure can was then sealed with a cap. 16.8 mL of liquefied petroleum gas (0.49 MPa (25°C)) was then filled under pressure as a propellant. A spray button (nozzle hole diameter φ0.6 mm) was attached to the aerosol valve, and a metered-dose aerosol was obtained with a spray volume of 0.2 mL per push and an ejection amount of transfluthrin of 16 mg.

[0050] (Comparative Example 5) A metered dose aerosol with a spray amount of 0.2 mL per push and an ejection amount of transfluthrin of 16 mg was obtained in the same manner as in Comparative Example 4, except that the spray button was changed to one with an orifice diameter of φ0.23 mm.

[0051] [Table 2]

[0052] 3.Measurement of injection time A laser diffraction particle size analyzer (Microtrac-Bell Corporation, LDSA-1400A) was placed 5 cm in a straight line in the direction of spray (horizontal) from the nozzle of the metered-volume aerosol, with the laser beam hitting the sample perpendicular to the spray direction. The spray button was pressed once (one push) to spray the sample, and a video of the spray was recorded. The video was then played back, and the longest continuous time during which the laser beam could be seen to be illuminated by the spray particles was measured in 0.01-second increments. Note that interruptions in the laser beam illumination of 0.05 seconds or less were considered continuous, and the measurement was terminated when the laser beam did not illuminate for 0.06 seconds or more. The final time the laser beam was illuminated was taken as the measurement time. The results are shown in Tables 3 and 4.

[0053] 4. Insecticidal efficacy test against Culex pipiens mosquitoes (Check insecticidal effectiveness immediately after spraying) A cage (a 25cm x 25cm 16-mesh cage folded in half and stapled around the edges to form a cylinder) containing 10 Culex pipiens mosquitoes was prepared as the test insects. As shown in Figure 1, an 8-tatami room (volume 31.1 m) 3 Cages containing Culex pipiens mosquitoes were placed at the four corners (corners B to E) of test chamber 10 (Fig. 1), one at a height of 0 cm from the floor and the other at a height of 75 cm from the floor. The spray button of a metered-dose aerosol was operated once (one push) at a height of 1 m from the floor in corner B, at a 45-degree angle diagonally upward, toward center A. The time until the Culex pipiens mosquitoes were knocked down (they fell over and became immobile) was measured, and KT50 (minutes) (the time required for 50% of the Culex pipiens mosquitoes to be knocked down) was calculated using the probit method. The test was performed three times, and the average was calculated. The results are shown in Table 3.

[0054] (Check insecticidal effectiveness 3 hours after spraying) A cage (a 25cm x 25cm 16-mesh cage folded in half and stapled around the edges to form a cylinder) containing 10 Culex pipiens mosquitoes was prepared as the test insects. As shown in Figure 1, an 8-tatami room (volume 31.1 m) 3 The spray button of a metered-dose aerosol was operated once (one push) at a height of 1 m from the floor in corner B of test chamber 10, at a 45-degree angle diagonally upwards, toward center A. Test chamber 10 was left sealed, and after 3 hours, cages containing Culex pipiens mosquitoes were placed on the floor (height 0 cm) and at a height of 75 cm from the floor in the four corners (corners B to E) of test chamber 10. The time until the Culex pipiens mosquitoes were knocked down was measured, and KT50 (minutes) was calculated using the probit method. The test was performed three times and the average was calculated. The results are shown in Table 4.

[0055] [Table 3]

[0056] [Table 4]

[0057] As shown in Table 3, the average KT50 for all metered dose aerosols was approximately 3 minutes immediately after spraying. In contrast, as shown in Table 4, differences were observed in the average KT50 three hours after spraying. Examples 1 to 4 and Comparative Examples 1 and 2 are examples in which the spray volume per push was 1 mL and the nozzle hole diameter of the spray button or the area of ​​the stem hole was changed. Examples 1 and 2 had significantly shorter average KT50 values ​​than Comparative Example 1, and Examples 3 and 4 had significantly shorter average KT50 values ​​than Comparative Example 2. Example 5 and Comparative Example 3 are examples in which the spray volume per push was 2.2 mL and the nozzle hole diameter of the spray button was changed. Example 5 had significantly shorter average KT50 values ​​than Comparative Example 3. Comparative Examples 4 and 5 were examples in which the spray volume per push was 0.2 mL, and Comparative Examples 4 and 5 had similar average KT50 values ​​three hours after spraying, regardless of the spray time. These results indicate that the duration of drug release varies depending on the spray duration for metered-dose aerosols capable of spraying large volumes of 1.0 mL or more.

[0058] <Test Example 2: Insecticidal efficacy test against cockroaches> 1. Stock Solution Preparation Stock solution 4 was prepared by measuring out 0.5 g of imiprothrin and 10 g of isopropyl myristate, adding No. 1 kerosene (normal paraffin, "Neothiosol" manufactured by Chuo Kasei Co., Ltd., carbon number 11 to 15, specific gravity 0.761 (15°C)) and making up to 100 mL.

[0059] 2. Preparation of metered dose aerosol According to Table 5, fixed dose aerosols of Examples 6 to 9 and Comparative Examples 6 and 7 were prepared.

[0060] Example 6 46 mL of concentrate 4 was filled into an aerosol pressure can (volume 294 mL), and the aerosol valve (amount per injection: 1.0 mL, stem hole area: 1.4 mm) was attached. 2 The aerosol pressure can was then sealed with a cap. 154 mL of dimethyl ether (DME) was then filled under pressure as a propellant. A spray button (nozzle hole diameter φ1.6 mm) was attached to the aerosol valve, and a metered-dose aerosol was obtained with a spray volume of 1.0 mL per push and an ejection amount of 1.2 mg of imiprothrin.

[0061] Example 7 A metered dose aerosol with a spray amount of 1.0 mL per push and an ejection amount of 1.2 mg of imiprothrin was obtained in the same manner as in Example 6, except that the spray button was changed to one with an orifice diameter of φ0.6 mm.

[0062] (Comparative Example 6) A metered dose aerosol with a spray volume of 1.0 mL per push and an ejection amount of 1.2 mg of imiprothrin was obtained in the same manner as in Example 6, except that the spray button was changed to one with an orifice diameter of 0.4 mm.

[0063] Example 8 The aerosol valve has a single injection volume of 1.0 mL and a stem hole area of ​​0.5 mm. 2 A metered dose aerosol spray with a spray amount of 1.0 mL per push and an ejection amount of 1.2 mg of imiprothrin was obtained in the same manner as in Example 6, except that the above was changed to the above.

[0064] Example 9 The aerosol valve has a single injection volume of 1.0 mL and a stem hole area of ​​0.28 mm. 2 A metered dose aerosol spray with a spray amount of 1.0 mL per push and an ejection amount of 1.2 mg of imiprothrin was obtained in the same manner as in Example 6, except that the above was changed to the above.

[0065] (Comparative Example 7) The aerosol valve has a single injection volume of 1.0 mL and a stem hole area of ​​0.13 mm. 2 A metered dose aerosol spray with a spray amount of 1.0 mL per push and an ejection amount of 1.2 mg of imiprothrin was obtained in the same manner as in Example 6, except that the above was changed to the above.

[0066] [Table 5]

[0067] 3.Measurement of injection time The spray time of the metered dose aerosol was measured in the same manner as in Test Example 1. The results are shown in Table 6.

[0068] 4. Insecticidal efficacy test against Smoky brown cockroaches As shown in Figure 2, a vinyl chloride cylinder 2 (diameter φ50 cm, height 15 cm) was placed on the floor covered with filter paper 1, and the interior of the cylinder was used as the test area. Calcium carbonate was applied to the inner sidewall of cylinder 2 to prevent the test insects from climbing up. A mark was made on filter paper 1 in the test area, close to the inner sidewall of cylinder 2, as the injection target point 3. One female Smoky Brown cockroach 5 was released into the test area as a test insect, and after leaving it for a while to acclimate, when Smoky Brown cockroach 5 reached target point 3, the spray button of a metered-dose aerosol sprayer was operated once (one push) at Smoky Brown cockroach 5 from a distance of 50 cm. The time until the Smoky Brown cockroach was knocked down (turned over and unable to move) was measured. The test was performed three times, and the average was calculated. The results are shown in Table 6.

[0069] [Table 6]

[0070] Examples 6-7 and Comparative Example 6 are examples in which the nozzle hole diameter of the spray button was changed in a metered dose aerosol with a spray volume of 1 mL per push, and Examples 8-9 and Comparative Example 7 are examples in which the area of ​​the stem hole was changed. From the results in Table 6, it was found that Examples 6 and 7, with spray times of 0.3 seconds and 0.73 seconds, respectively, had significantly shorter knockdown times for Smoky-brown cockroaches than Comparative Example 6, with a spray time of 1.36 seconds, and that Examples 8 and 9, with spray times of 0.58 seconds and 0.73 seconds, respectively, had significantly shorter knockdown times for Smoky-brown cockroaches than Comparative Example 7, with a spray time of 1.2 seconds.

[0071] <Test Example 3: Insecticidal efficacy test against houseflies> 1. Stock Solution Preparation Stock solution 5 was prepared by measuring out 1.4 g of phthalthrin and adding No. 1 kerosene (normal paraffin, "Neothiosol" manufactured by Chuo Kasei Co., Ltd., carbon number 11 to 15, specific gravity 0.761 (15°C)) and making up to 100 mL.

[0072] 2. Preparation of metered dose aerosol According to Table 7, fixed dose aerosols of Examples 10 and 11 and Comparative Example 8 were prepared.

[0073] Example 10 40 mL of concentrate 5 was filled into an aerosol pressure can (volume 294 mL) and fitted with an aerosol valve (single injection volume 1.0 mL, stem hole area 1.4 mm 2 The aerosol pressure can was then sealed with a cap. 160 mL of liquefied petroleum gas (0.29 MPa (25°C)) was then filled under pressure as a propellant. A spray button (nozzle hole diameter φ1.6 mm) was attached to the aerosol valve, and a metered-dose aerosol was obtained with a spray volume of 1.0 mL per push and an ejection volume of 2.8 mg of phthalthrin.

[0074] Example 11 A metered dose aerosol with a spray volume of 1.0 mL per push and an ejection volume of 2.8 mg of phthalthrin was obtained in the same manner as in Example 10, except that the spray button was changed to one with a nozzle hole diameter of 0.6 mm.

[0075] (Comparative Example 8) A metered dose aerosol with a spray volume of 1.0 mL per push and an ejection volume of 2.8 mg of phthalthrin was obtained in the same manner as in Example 10, except that the spray button was changed to one with a nozzle hole diameter of 0.4 mm.

[0076] [Table 7]

[0077] 3.Measurement of injection time The spray time of the metered dose aerosol was measured in the same manner as in Test Example 1. The results are shown in Table 8.

[0078] 4. Insecticidal efficacy test against houseflies 8 tatami mat space (volume 31.1m 3 A female housefly was released as a test insect into a test chamber. When the housefly landed on the wall, the spray button of a metered-volume aerosol sprayer was pressed once (one push) at the housefly from a distance of about 50 cm. The time until the housefly fell and was knocked down was measured. The test was performed three times and the average was calculated. The results are shown in Table 8.

[0079] [Table 8]

[0080] The results in Table 8 show that Examples 10 and 11, in which the injection times were 0.32 seconds and 0.74 seconds, respectively, had significantly shorter knockdown times for houseflies than Comparative Example 8, in which the injection time was 1.36 seconds.

[0081] <Test Example 4: Fragrance Efficacy Confirmation Test> 1. Stock Solution Preparation 0.5 g of linalool was measured out, and absolute ethanol (specific gravity 0.785 (25°C)) was added to the solution to make up to 100 mL, thereby preparing stock solution 6.

[0082] 2. Preparation of metered dose aerosol According to Table 9, metered dose aerosols of Example 12 and Comparative Example 9 were prepared.

[0083] Example 12 40 mL of concentrate 6 was filled into an aerosol pressure can (volume 294 mL) and fitted with an aerosol valve (single injection volume 1.0 mL, stem hole area 1.4 mm 2 The aerosol pressure can was then sealed with a cap. 160 mL of liquefied petroleum gas (0.29 MPa (25°C)) was then filled under pressure as a propellant. A spray button (nozzle hole diameter φ1.6 mm) was attached to the aerosol valve, and a metered-dose aerosol was obtained with a spray volume of 1.0 mL per push and a discharge amount of 1.0 mg of linalool.

[0084] (Comparative Example 9) A metered dose aerosol was obtained in the same manner as in Example 12, except that the spray button was changed to one with a nozzle hole diameter of φ0.4 mm, with a spray volume of 1.0 mL per push and an ejection volume of 1.0 mg of linalool.

[0085] [Table 9]

[0086] 3.Measurement of injection time The spray time of the metered dose aerosol was measured in the same manner as in Test Example 1. The results are shown in Table 10.

[0087] 4. Aroma sensory test (Sensory evaluation 10 seconds after spraying) As shown in Figure 3, a 6-tatami room (volume 25 m) 3 The spray button of the metered-dose aerosol was operated once (pushed once) from a height of 100 cm above the floor at center position F of first wall 21 of test chamber 20, directed toward third wall 23 opposite first wall 21 and approximately horizontal to the floor. 10 seconds after spraying, subjects stood at center position F of first wall 21, which was the spray position, center position G of second wall 22 perpendicular to first wall 21, and center position H of third wall 23 opposite first wall 21, and evaluated the fragrance intensity according to the evaluation criteria of the 6-point odor intensity rating system. The test was conducted three times, and the average value was rounded off to obtain a 6-point value. The results are shown in Table 10. [Evaluation criteria] 0: Odorless (a person with a normal sense of smell cannot smell anything) 1: Smell that can barely be detected (detection threshold concentration) 2: A weak odor that can be identified (recognition threshold concentration) 3: Easily detectable odors 4: Strong odor 5: Strong odor

[0088] (Sensory evaluation 30 minutes after spraying) After checking the scent intensity 10 seconds after spraying, the test chamber 20 was left sealed, and after 30 minutes, the scent intensity was evaluated while standing at the center positions F to H of each wall. The test was conducted three times, and the average value was rounded off to the nearest 6-point scale. The results are shown in Table 10.

[0089] [Table 10]

[0090] The results in Table 10 show that Example 12, which has an injection time of 0.31 seconds, has superior fragrance spread and intensity after 30 minutes compared to Comparative Example 9, which has an injection time of 1.35 seconds, and is also superior in fragrance durability even after 30 minutes have passed.

[0091] <Test Example 5: Sterilization Efficacy Confirmation Test> 1. Stock Solution Preparation Stock solution 7 was prepared by measuring out 20 g of isopropylmethylphenol (IPMP) and adding 99.5% ethanol (specific gravity 0.785 (25° C.)) to make up to 100 mL.

[0092] 2. Preparation of metered dose aerosol Example 13 60 mL of concentrate 7 was filled into an aerosol pressure can (volume 294 mL), and the aerosol valve (single injection volume 1.0 mL, stem hole area 1.4 mm) was attached. 2 The aerosol pressure can was then sealed with a cap. 140 mL of liquefied petroleum gas (0.49 MPa (25°C)) was then filled under pressure as a propellant. A spray button (nozzle hole diameter φ1.6 mm) was attached to the aerosol valve, and a metered-dose aerosol was obtained with a spray volume of 1.0 mL per push and a discharge volume of 60 mg of IPMP.

[0093] 3.Measurement of injection time The spray time of the metered dose aerosol was measured in the same manner as in Test Example 1. The results are shown in Table 11.

[0094] 4. Efficacy confirmation test Bathrooms in 10 general households were cleaned to remove pink slime (mainly caused by Rhodotorula (yeast) or Methylobacterium (bacteria)) and black mold (mainly caused by Cladosporium (fungi)). Two locations where pink slime or black mold frequently appeared were then selected. One of the locations was approached and the spray button of a metered-dose aerosol spray was pressed once (one push), and the treated area was designated the treated area. The other location was left untreated, and the area designated the untreated area. For each household, it was determined how many days after the bathroom cleaning and sample treatment that pink slime or black mold had appeared. The test was conducted during the period when pink slime and black mold are likely to grow (June to September, Japan). The results are shown in Table 11.

[0095] [Table 11]

[0096] The results in Table 11 show that pink slime or black mold developed in the untreated area within one week, whereas the treated area sprayed with the metered dose aerosol of Example 13 achieved a sterilizing and anti-fungal effect for more than 10 days.

[0097] Although the present invention has been described in detail and with reference to specific embodiments, it will be apparent to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the present invention. This application is based on a Japanese patent application (Patent Application No. 2017-238160) filed on December 12, 2017, the contents of which are incorporated herein by reference. [Explanation of symbols]

[0098] 1 filter paper 2 cylinders 3. Target Points 5. Black cockroach 10, 20 Test Rooms 21 The First Wall 22 The Second Wall 23 The Third Wall A Central section B~E corner F~H center position

Claims

1. A metered-amount aerosol that sprays a fixed amount of the aerosol composition in one spray operation, The aerosol composition comprises a concentrate containing a drug and a propellant, and is filled in a pressure-resistant container; The metered dose aerosol has a single spray volume of 1.0 to 3.0 mL and a single spray duration of 0.8 seconds or less.

2. 2. The metered dose aerosol according to claim 1, wherein the duration of each spray is 0.20 to 0.75 seconds.

3. The metered dose aerosol according to claim 1 or 2, wherein the concentrate further comprises a solvent.

4. The metered dose aerosol according to any one of claims 1 to 3, wherein the content of the drug in the concentrate is 0.01 to 70% by mass / volume.

5. 5. The metered dose aerosol according to claim 1, wherein the volume ratio of said concentrate to said propellant in said aerosol composition is from 1:99 to 50:

50.

6. The metered spray aerosol according to any one of claims 1 to 5, wherein the agent is at least one selected from the group consisting of pest control components, fragrance components, deodorizing components, and disinfecting / sterilizing components.

7. A method for spraying a metered-volume aerosol, in which a pressure-resistant container is filled with an aerosol composition comprising a drug-containing concentrate and a propellant, is used to spray a quantity of 1.0 to 3.0 mL per spray operation for a spray time of 0.8 seconds or less.

8. 1. A method for enhancing the efficacy of a drug in an aerosol composition delivered using a metered dose aerosol, comprising: A method for improving the efficacy of a drug, comprising spraying a fixed amount of the aerosol composition in the range of 1.0 to 3.0 mL within 0.8 seconds.

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