JP2024071611A - Fixed-dose aerosol, method for spraying fixed-dose aerosol, and method for improving the durability of drug effect - Google Patents

Abstract

[Problem] The object of the present invention is to provide a metered dose aerosol with improved efficacy and increased durability of the drug. [Solution] The metered dose aerosol of the present invention is a metered dose aerosol that sprays a fixed amount of the aerosol composition with one spray operation, the aerosol composition is composed of a concentrate containing the 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 time of 0.8 seconds or less. [Selected Figure] None

Description

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 that is sprayed when the metered dose aerosol is sprayed.

Fixed-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 one spray operation. Fixed-dose aerosols eject a set amount of drug in one spray operation, so there is little variation in the operating method used by the user (differences in the amount sprayed depending on the method of pressing the spray button or the time the button is pressed), and this has the advantage of less variation in effectiveness.

For example, Patent Document 1 discloses an aerosol for pest control equipped with an aerosol valve for fixed-dose spraying, with a volume of 0.35 to 0.9 mL per spray.

Japanese Patent Publication No. 2010-280633

As described above, the measurable effect of a fixed-amount aerosol spray used in the air, such as insecticide aerosol or fragrance aerosol, is stable, but if the amount sprayed each time is small, the user cannot fully feel the effect, and even if an effective amount of the drug is sprayed in one spray, the user may end up using the drug multiple times, resulting in excessive consumption. In addition, the measurable effect of the drug is limited in the conventional fixed-amount aerosol spray, and in order to maintain the effect, the spray operation must be repeated after a certain time has elapsed since the spray, which must be done frequently.
Therefore, an object of the present invention is to provide a metered dose aerosol which improves the efficacy of a medicine, prolongs its effect, and provides a real feeling when used.

After extensive research, the inventors have found that a metered-volume aerosol capable of spraying large volumes of 1.0 mL or more can increase the amount of medicine ejected while improving the feeling of use because a large amount is ejected per injection, and further that with a metered-volume aerosol that ejects large volumes, the duration of the medicine's effect varies depending on the injection time per injection, and that there is an optimal balance between the amount of aerosol composition ejected per injection and the injection time for which the medicine's effect can be sustained.

That is, the present invention is characterized by the following (1) to (8).
(1) A fixed-dose aerosol which sprays a fixed amount of an aerosol composition with one spray operation, said aerosol composition comprising a concentrate containing a drug and a propellant and filled in a pressure-resistant container, said fixed-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) above, wherein the concentrate further contains a solvent.
(4) The metered dose aerosol according to any one of (1) to (3), wherein the content of the drug in the concentrate is 0.01 to 70 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 an aerosol composition consisting of a drug-containing concentrate and a propellant is filled in a pressure-resistant container, the method comprising spraying a quantity of 1.0 to 3.0 mL per spray operation for a spray time of 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.

According to the fixed-volume 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 with one spray operation, and furthermore, the durability of the effect 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, wasteful overuse can be avoided, and the effect of the drug can be sustained with one spray operation.

FIG. 1 is a plan view for explaining the test chamber used in Test Example 1. FIG. 2 is a perspective view for explaining the test method of Test Example 2. FIG. 3 is a plan view for explaining the test chamber used in Test Example 4.

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

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

(undiluted solution)
The concentrate constituting the aerosol composition of the present invention contains at least a drug as an active ingredient. The active ingredient refers to a substance that exerts some kind of action when a metered-dose aerosol is used, and includes, but is not limited to, pest control ingredients, fragrance ingredients, deodorizing ingredients, disinfecting/bactericidal ingredients, etc.

The pest control component is a component that can kill, repel, knock down, etc., a target pest. The type of the pest control component is not particularly limited, and any known compound can be used.
Examples of pest control components include pyrethroid compounds such as permethrin, pyrethrin, 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, Japanese cypress oil, jasmine oil, neroli oil, peppermint oil, bergamot oil, butygrain oil, lemon oil, lemongrass oil, cinnamon oil, citronella oil, geranium oil, citral, l-menthol Various essential oil components such as 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.

The pest control component may be appropriately selected according to the type of target pest, such as mosquitoes, flies, moths, bees, stink bugs, cockroaches, ants, spiders, pillbugs, mites, lice, centipedes, caterpillars, millipedes, spiders, horseflies, blackflies, moths, termites, midges, leafhoppers, wood beetles, ground beetles, earwigs, silverfish, longhorn beetles, dermestid beetles, booklice, burrs, and rice moths.
For flying pests such as mosquitoes, flies, moths, bees, horseflies, black flies, midges, leafhoppers, moths, burrs, and rice moths, transfluthrin, metofluthrin, profluthrin, phthalthrin, prallethrin, momfluorothrin, etc. are suitable. For crawling pests such as cockroaches, stink bugs, ants, spiders, pillbugs, mites, lice, centipedes, caterpillars, millipedes, spiders, termites, wood beetles, ground beetles, earwigs, silverfish, etc., phthalthrin, prallethrin, imiprothrin, permethrin, fenothrin, etc. are suitable.

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 cineol. These may be used alone or in combination of two or more.

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 crotolate, 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.

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.

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

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

The stock solution may contain a solvent for the purpose of adjusting the viscosity of the stock solution, improving production suitability, increasing the penetration of the drug against pests, etc. Examples of such solvents include the above-mentioned glycol ethers, hydrocarbon solvents, alcohol solvents, aromatic solvents, ester solvents, etc. Water and surfactants may also be used.
Examples of the hydrocarbon solvent include aliphatic hydrocarbons and alicyclic hydrocarbons such as paraffinic hydrocarbons and naphthenic hydrocarbons, and kerosene such as JIS No. 1 kerosene is 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 the alcohol-based solvent 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-based solvents include isopropyl myristate, hexyl laurate, and isopropyl palmitate.

The solvent content in the concentrate is preferably 30 to 99.99% by mass/volume. Having the solvent in the concentrate at 30% by mass/volume or more can improve production suitability, and a content of 99.99% by mass/volume or less is preferable because it ensures sufficient drug effectiveness. The solvent content is more preferably at a lower limit of 35% by mass/volume or more, even more preferably at a higher limit of 50% by mass/volume, and more preferably at an upper limit of 99.9% by mass/volume or less, even more preferably at a higher limit of 99.5% by mass/volume or less.

The concentrate may contain other ingredients as long as they do not impair the effects of the present invention. Examples of other ingredients include preservatives, pH adjusters, UV absorbers, inorganic substances, surfactants, dissolution aids, etc.

The content of the concentrate in the aerosol composition can be changed as appropriate depending on the purpose of the metered-dose aerosol and the combination with the propellant, and is not particularly limited, but can be, for example, 1 to 50% by volume in the aerosol composition. If the concentrate is 1% by volume or more in the aerosol composition, a sufficient drug effect can be obtained, and if it is 50% by volume or less, the concentrate can be sprayed as spray particles, so that when used indoors, for example, contamination of furniture, floors, walls, etc. by the concentrate can be reduced. The content of the concentrate in the aerosol composition is preferably 3% by volume or more at the lower limit, more preferably 5% by volume or more, and more preferably 40% by volume or less at the upper limit, even more preferably 30% by volume or less.

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

The propellant content in the aerosol composition can be changed as appropriate depending on the purpose of the metered-dose aerosol and the combination with the concentrate, and is not particularly limited, but can be, for example, 50 to 99% by volume in the aerosol composition. If the propellant content in the aerosol composition is 50% by volume or more, the concentrate can be sprayed as spray particles, making it easier for the drug to spread and making it easier for the drug's effects to last. If the propellant content is 99% by volume or less, the drug's effects can be sufficiently achieved. The propellant content in the aerosol composition is preferably 60% by volume or more at the lower limit, more preferably 70% by volume or more, and more preferably 97% by volume or less at the upper limit, even more preferably 95% by volume or less.

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 using such a volume ratio, it is possible to obtain a sufficient effect of the drug.

(Fixed-dose aerosol)
The constant-quantity aerosol of the present invention is constructed by filling the above-mentioned concentrate and propellant into a pressure-resistant aerosol container, and closing the opening of the pressure-resistant container with an aerosol valve.

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

(Aerosol valve)
The aerosol valve includes an opening/closing member for switching between communication and cut-off between the inside and outside of the pressure-resistant container by the user operating the ejection member, a housing to which the opening/closing member is attached, and a mounting member for holding the housing at 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 ejection member. The sliding of the stem switches between communication (ejection state) and cut-off (non-ejection 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 sending the taken-in aerosol composition to the ejection 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 sending the aerosol composition taken in the housing to the ejection member. The path from the housing hole to the stem hole constitutes an internal passage through which the aerosol composition passes.

In the present invention, the aerosol valve is a fixed-volume type aerosol valve that sprays a fixed amount by operating the spray member once. The spray amount 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 an aerosol composition with a predetermined amount of spray per operation in the range of 1.0 to 3.0 mL, a predetermined fixed amount in the range of 1.0 to 3.0 mL can be sprayed in one spray operation, making it possible to spray a large amount of medicine. The spray amount of the aerosol valve can be appropriately set to a predetermined amount as long as it is within the above range.

(Injection member)
The spray member (spray button) is a member attached to the pressure 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 container via the stem hole of the aerosol valve passes, and with a nozzle through which the aerosol composition is sprayed.

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.

(Injection pressure)
In the fixed-dose aerosol of the present invention, as described above, the concentrate and the propellant, i.e., the aerosol composition, are filled in the pressure-resistant aerosol container, and a fixed amount of the aerosol composition is sprayed by pressing the spray button once. 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 to a desired range.
The spray pressure can be measured by spraying the aerosol composition toward the center of a circular flat plate having 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 constant-volume spray aerosol under room temperature conditions of 25° C., and calculating the average of the maximum value as the spray load.

(Injection time)
The fixed-dose aerosol of the present invention has an ejection time of 0.8 seconds or less per ejection operation. Although the reason why the effects of the present invention are obtained is unclear, it is believed that by ejecting a predetermined amount of the aerosol composition, which is in the range of 1.0 to 3.0 mL per ejection, within 0.8 seconds, the volatility of the drug can be efficiently increased, thereby improving the efficacy of the drug and increasing the duration of its effect.
The injection time for one injection operation is preferably within 0.75 seconds, more preferably from 0.10 to 0.75 seconds, even more preferably from 0.20 to 0.75 seconds, and particularly preferably from 0.25 to 0.75 seconds.

In the present invention, examples of methods for adjusting the injection time for one injection operation include adjusting the size of the nozzle of the injection button, adjusting the injection pressure of a fixed-dose aerosol, adjusting the stem hole diameter of an aerosol valve, adjusting the propellant pressure, and combinations of these.

By using the metered dose aerosol of the present invention to spray a fixed amount of the 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 effect.

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.

<Test Example 1: Insecticidal Efficacy Confirmation Test Against Culex pipiens Mosquito>
1. Preparation of Stock Solutions 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 to prepare stock solutions 1 to 3.

2. Preparation of Metered-Dose Aerosols According to Table 2, metered-dose aerosols of Examples 1 to 5 and Comparative Examples 1 to 5 were prepared.

Example 1
An aerosol pressure canister (volume 294 mL) was filled with 12.8 mL of concentrate 1 and closed with an aerosol valve (amount per injection 1.0 mL, stem hole area 1.4 mm ² ). Subsequently, 187.2 mL of liquefied petroleum gas (0.49 MPa (25° C.)) was pressurized and filled as a propellant.
A spray button (nozzle hole diameter φ1.6 mm) was attached to the aerosol valve to obtain a metered-dose aerosol with a spray volume of 1.0 mL per push and a discharge volume of 16 mg of transfluthrin.

Example 2
A constant-dose aerosol with a spray volume of 1.0 mL per push and a discharge 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 a nozzle hole diameter of φ0.6 mm.

(Comparative Example 1)
A constant-dose aerosol with a spray volume of 1.0 mL per push and a discharge 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 a nozzle hole diameter of φ0.4 mm.

Example 3
A metered-dose aerosol with a per-push spray volume of 1.0 mL and an ejection volume of 16 mg of transfluthrin was obtained in the same manner as in Example 1, except that the aerosol valve was changed to ^one with a per-push spray volume of 1.0 mL and a stem hole area of 0.5 mm2.

Example 4
A metered-dose aerosol with a per-push spray volume of 1.0 mL and an ejection volume of 16 mg of transfluthrin was obtained in the same manner as in Example 1, except that the aerosol valve was changed to ^one with a per-push spray volume of 1.0 mL and a stem hole area of 0.28 mm2.

(Comparative Example 2)
A metered-dose aerosol with a per-push spray volume of 1.0 mL and an ejection volume of 16 mg of transfluthrin was obtained in the same manner as in Example 1, except that the aerosol valve was changed to ^one with a per-push spray volume of 1.0 mL and a stem hole area of 0.13 mm2.

Example 5
An aerosol pressure canister (volume 294 mL) was filled with 12.8 mL of concentrate 2 and closed with an aerosol valve (amount per injection 2.2 mL, stem hole area 1.4 mm ² ). Subsequently, 187.2 mL of liquefied petroleum gas (0.49 MPa (25° C.)) was pressurized and filled as a propellant.
A spray button (nozzle hole diameter φ1.6 mm) was attached to the aerosol valve to obtain a metered-dose aerosol with a spray volume of 2.2 mL per push and a discharge volume of 16 mg of transfluthrin.

(Comparative Example 3)
A constant-dose aerosol with a spray volume of 2.2 mL per push and a discharge 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 a nozzle hole diameter of φ0.6 mm.

(Comparative Example 4)
An aerosol pressure canister (volume 59 mL) was filled with 3.2 mL of concentrate 3 and closed with an aerosol valve (amount per injection 0.2 mL, stem hole area 0.4 mm ² ). Subsequently, 16.8 mL of liquefied petroleum gas (0.49 MPa (25° C.)) was pressurized and filled as a propellant.
A spray button (nozzle hole diameter φ0.6 mm) was attached to the aerosol valve to obtain a metered-dose aerosol with a spray volume of 0.2 mL per push and an ejection volume of 16 mg of transfluthrin.

(Comparative Example 5)
A constant-dose aerosol with a spray amount of 0.2 mL per push and a discharge amount of 16 mg of transfluthrin was obtained in the same manner as in Comparative Example 4, except that the spray button was changed to one with a nozzle hole diameter of φ0.23 mm.

3. Measurement of spray time A laser light diffraction particle size measuring device (Microtrac Bell Corporation's "LDSA-1400A") was installed at a position 5 cm away from the nozzle of the constant-volume aerosol in a straight line in the spray direction (horizontal direction), so that the laser light was applied perpendicular to the spray direction. The spray button was operated once (one push) to spray, and a video of the spray was taken. The video was played back, and the longest continuous time during which the laser light could be confirmed to be lit by the spray particles was measured in 0.01 second units. Note that interruptions in the laser light lighting of 0.05 seconds or less were considered to be continuous, and the measurement was terminated when the laser light was not lit for 0.06 seconds or more, and the final time the laser light was lit was taken as the measurement time. The results are shown in Tables 3 and 4, respectively.

4. Insecticidal efficacy test against Culex pipiens mosquitoes (verification of insecticidal efficacy immediately after spraying)
A cage (a 16-mesh cage measuring 25 cm long x 25 cm wide, folded in half and stapled around the edges to form a cylinder) containing 10 Culex pipiens mosquitoes was prepared as test insects.
As shown in Figure 1, cages containing Culex pipiens pallens 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 a test room 10 of an 8-tatami room (volume 31.1 m3). The spray button of a constant-volume aerosol was operated once (one push) toward the center A at a 45-degree angle diagonally upward from a height of 1 m from the floor in corner B. The time until the Culex pipiens pallens was knocked down (it fell over and could not move) was measured, and KT50 (min) (the time required for 50% of the Culex pipiens pallens to be knocked down) was calculated by the probit method. The test was performed three times and the average was calculated. The results are shown in Table 3.

(Verification of insecticidal effect 3 hours after spraying)
A cage (a 16-mesh cage measuring 25 cm long x 25 cm wide, folded in half and stapled around the edges to form a cylinder) containing 10 Culex pipiens mosquitoes was prepared as test insects.
As shown in Figure 1, the spray button of a constant-volume aerosol was operated once ( ^one push) toward the center A at a 45 degree angle from a height of 1 m above the floor at corner B of a test room 10 of an 8-tatami room (volume 31.1 m3). The test room 10 was left sealed, and after 3 hours, cages containing Culex pipiens pallens were placed on the floor (height 0 cm) and at a height of 75 cm above the floor at the four corners (corners B to E) of the test room 10. The time until the Culex pipiens pallens was knocked down was measured, and KT50 (min) was calculated by the probit method. The test was performed three times, and the average was calculated. The results are shown in Table 4.

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

<Test Example 2: Insecticidal Efficacy Confirmation Test Against Cockroaches>
1. Preparation of Stock Solution 0.5 g of imiprothrin and 10 g of isopropyl myristate were measured out, and No. 1 kerosene (normal paraffin, "Neothiosol" manufactured by Chuo Kasei Co., Ltd., carbon number 11 to 15, specific gravity 0.761 (15°C)) was added and made up to 100 mL to prepare stock solution 4.

2. Preparation of Metered-Dose Aerosols According to Table 5, metered-dose aerosols of Examples 6 to 9 and Comparative Examples 6 to 7 were prepared.

Example 6
An aerosol pressure canister (volume 294 mL) was filled with 46 mL of concentrate 4 and closed with an aerosol valve (amount per injection 1.0 mL, stem hole area 1.4 mm ² ). Subsequently, 154 mL of dimethyl ether (DME) was filled under pressure as a propellant.
A spray button (nozzle hole diameter φ1.6 mm) was attached to the aerosol valve to obtain a metered-dose aerosol with a spray volume of 1.0 mL per push and an ejection volume of 1.2 mg of imiprothrin.

(Example 7)
A constant-dose aerosol with a spray amount of 1.0 mL per push and a discharge 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 a nozzle hole diameter of φ0.6 mm.

(Comparative Example 6)
A constant-dose aerosol with a spray amount of 1.0 mL per push and a discharge 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 a nozzle hole diameter of φ0.4 mm.

(Example 8)
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 aerosol valve was changed to one with a single spray volume of ^1.0 mL and a stem hole area of 0.5 mm2.

Example 9
A metered-dose aerosol with a spray volume of 1.0 mL per push and a discharge volume of 1.2 mg of imiprothrin was obtained in the same manner as in Example 6, except that the aerosol valve was changed to one with a single spray volume of ^1.0 mL and a stem hole area of 0.28 mm2.

(Comparative Example 7)
A metered-dose aerosol with a spray volume of 1.0 mL per push and a discharge volume of 1.2 mg of imiprothrin was obtained in the same manner as in Example 6, except that the aerosol valve was changed to one with a single spray volume of ^1.0 mL and a stem hole area of 0.13 mm2.

3. Measurement of spray time The spray time of the constant-dose aerosol was measured in the same manner as in Test Example 1. The results are shown in Table 6.

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 inside of the cylinder was used as the test area. Calcium carbonate was applied to the inner side wall of the cylinder 2 to prevent the test insects from crawling up. A mark was made on the filter paper 1 in the test area at a position close to the inner side wall of the cylinder 2 as the target point 3 for injection.
A female Smoky Brown Cockroach 5 was released as a test insect in the test area, and after leaving it for a while to acclimate, when the Smoky Brown Cockroach 5 reached the target point 3, the spray button of the fixed-dose aerosol was operated once (one push) toward the Smoky Brown Cockroach 5 from a distance of 50 cm. The time until the Smoky Brown Cockroach was knocked down (turned over and could not move) was measured. The test was performed three times, and the average was calculated. The results are shown in Table 6.

Examples 6 to 7 and Comparative Example 6 are examples in which the nozzle hole diameter of the spray button was changed in a constant-dose aerosol with a spray volume of 1 mL per push, and Examples 8 to 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, which have spray times of 0.3 and 0.73 seconds, had significantly shorter knockdown times for Smoky Brown cockroaches than Comparative Example 6, which had a spray time of 1.36 seconds, and Examples 8 and 9, which have spray times of 0.58 and 0.73 seconds, had significantly shorter knockdown times for Smoky Brown cockroaches than Comparative Example 7, which had a spray time of 1.2 seconds.

<Test Example 3: Insecticidal Efficacy Confirmation Test Against Houseflies>
1. Preparation of Stock Solution 1.4 g of phthalthurin was measured out, and No. 1 kerosene (normal paraffin, "Neothiosol" manufactured by Chuo Kasei Co., Ltd., carbon number 11 to 15, specific gravity 0.761 (15°C)) was added thereto and made up to 100 mL to prepare stock solution 5.

2. Preparation of Metered-Dose Aerosols According to Table 7, metered-dose aerosols of Examples 10 and 11 and Comparative Example 8 were prepared.

Example 10
An aerosol pressure canister (volume 294 mL) was filled with 40 mL of concentrate 5 and closed with an aerosol valve (amount per injection 1.0 mL, stem hole area 1.4 mm ² ). Subsequently, 160 mL of liquefied petroleum gas (0.29 MPa (25° C.)) was pressurized and filled as a propellant.
A spray button (nozzle hole diameter φ1.6 mm) was attached to the aerosol valve to obtain a metered-dose aerosol with a spray volume of 1.0 mL per push and an ejection volume of 2.8 mg of phthalthrin.

(Example 11)
A constant-dose aerosol was obtained in the same manner as in Example 10, except that the spray button was changed to one with an orifice diameter of φ0.6 mm, with a spray volume of 1.0 mL per push and an ejection volume of 2.8 mg of phthalthrin.

(Comparative Example 8)
A constant-dose aerosol was obtained in the same manner as in Example 10, except that the spray button was changed to one with an orifice diameter of φ0.4 mm, with a spray volume of 1.0 mL per push and an ejection volume of 2.8 mg of phthalthrin.

3. Measurement of spray time The spray time of the constant-dose aerosol was measured in the same manner as in Test Example 1. The results are shown in Table 8.

4. Insecticidal efficacy test against houseflies One female house fly was released as a test insect into a test room of 8 tatami mats (volume 31.1 ^m3 ). When the house fly landed on the wall, the spray button of a metered-dose aerosol was operated once (one push) toward the house fly from a distance of about 50 cm. The time until the house fly 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.

The results in Table 8 show that Examples 10 and 11, with injection times of 0.32 seconds and 0.74 seconds, had significantly shorter knockdown times for houseflies than Comparative Example 8, with an injection time of 1.36 seconds.

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

2. Preparation of Metered-Dose Aerosols According to Table 9, metered-dose aerosols of Example 12 and Comparative Example 9 were prepared.

Example 12
An aerosol pressure canister (volume 294 mL) was filled with 40 mL of concentrate 6 and closed with an aerosol valve (amount per injection 1.0 mL, stem hole area 1.4 mm ² ). Subsequently, 160 mL of liquefied petroleum gas (0.29 MPa (25° C.)) was pressurized and filled as a propellant.
A spray button (nozzle hole diameter φ1.6 mm) was attached to the aerosol valve to obtain a metered-dose aerosol with a spray volume of 1.0 mL per push and a discharge volume of 1.0 mg of linalool.

(Comparative Example 9)
A constant-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 a discharge volume of 1.0 mg of linalool.

3. Measurement of spray time The spray time of the constant-dose aerosol was measured in the same manner as in Test Example 1. The results are shown in Table 10.

4. Aroma sensory test (sensory evaluation 10 seconds after spraying)
As shown in Fig. 3, the spray button of the metered-volume aerosol was operated once ( ^one push) from a height of 100 cm from the floor at the center position F of the first wall 21 of the test room 20 of a 6-tatami room (volume 25 m3) toward the third wall 23 facing the first wall 21 almost horizontally to the floor surface. 10 seconds after spraying, the subjects stood at the spray position, which was the center position F of the first wall 21, the center position G of the second wall 22 perpendicular to the first wall 21, and the center position H of the third wall 23 facing the first wall 21, and evaluated the fragrance intensity according to the evaluation criteria of the 6-stage odor intensity rating method. The test was performed three times, and the average value was rounded off to a 6-stage value. The results are shown in Table 10.
〔Evaluation criteria〕
0: Odorless (a person with a normal sense of smell cannot detect any odor)
1: Smell that can just be detected (detection threshold concentration)
2: Weak odor that can be identified (recognition threshold concentration)
3: Easily detectable odor 4: Strong odor 5: Overpowering odor

(Sensory evaluation 30 minutes after spraying)
After checking the fragrance intensity 10 seconds after the spray, the test room 20 was left sealed, and after 30 minutes, the fragrance intensity was evaluated when standing at the center positions F to H of each wall. The test was performed three times, and the average value was rounded off to the nearest 6-point value. The results are shown in Table 10.

The results in Table 10 show that Example 12, which has an injection time of 0.31 seconds, is superior in 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.

<Test Example 5: Sterilization Efficacy Confirmation Test>
1. Preparation of Stock Solution 20 g of isopropylmethylphenol (IPMP) was measured out, and 99.5% ethanol (specific gravity 0.785 (25° C.)) was added thereto to make up to 100 mL, thereby preparing stock solution 7.

2. Preparation of a fixed-dose aerosol (Example 13)
An aerosol pressure canister (volume 294 mL) was filled with 60 mL of concentrate 7 and closed with an aerosol valve (amount per injection 1.0 mL, stem hole area 1.4 mm ² ). Subsequently, 140 mL of liquefied petroleum gas (0.49 MPa (25° C.)) was pressurized and filled as a propellant.
An ejection button (with an ejection hole diameter of φ1.6 mm) was attached to the aerosol valve, and a constant-dose ejection type aerosol was obtained with an ejection amount of 1.0 mL per push and a discharge amount of 60 mg of IPMP.

3. Measurement of spray time The spray time of the constant-dose aerosol was measured in the same manner as in Test Example 1. The results are shown in Table 11.

4. Efficacy confirmation test The bathrooms of 10 general households were cleaned to remove pink slime (mainly caused by Rhodotorula (yeast) or Methylobacterium (bacteria)) and black mold (mainly caused by Cladosporium (fungus)). After that, two locations where pink slime and black mold frequently occur were selected. The spray button of a metered-dose aerosol was operated once (one push) toward one of these locations, and the treated location was designated as the treatment area. The other location was left untreated, and the agent was not allowed to adhere to it. For each household, it was confirmed how many days after the bathroom cleaning and sample treatment date 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.

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

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.

1 Filter paper 2 Cylinder 3 Target point 5 Smoky brown cockroach 10, 20 Test chamber 21 First wall 22 Second wall 23 Third wall A Center B to E Corner F to H Center position

Claims (8)

A metered-volume 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 fixed-dose aerosol has a single spray amount of 1.0 to 3.0 mL and a single spray time of 0.8 seconds or less. The metered dose aerosol according to claim 1, wherein the duration of each spray is 0.20 to 0.75 seconds. The metered dose aerosol according to claim 1 or 2, wherein the concentrate further contains a solvent. 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 mass/volume %. The metered dose aerosol according to any one of claims 1 to 4, wherein the volume ratio of the concentrate to the propellant in the aerosol composition is 1:99 to 50:50. The metered-dose 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/bactericidal components. A method for spraying a fixed-volume aerosol in which a fixed-volume aerosol composition consisting of a drug-containing concentrate and a propellant is filled in a pressure-resistant container, and the amount sprayed is 1.0 to 3.0 mL per spray operation and the spray time is within 0.8 seconds. 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 said aerosol composition in the range of 1.0 to 3.0 mL within 0.8 seconds.

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