JP7765532B2 - Metered-dose aerosol, method for spraying metered-dose aerosol, and method for improving the durability of drug effect - Google Patents

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 ejected when the metered dose aerosol is sprayed.

Metered-dose aerosols are known that spray a fixed amount of an aerosol composition consisting of a concentrate containing the active ingredient drug and a propellant with a single spray operation. Because metered-dose aerosols eject a predetermined amount of drug with a single spray operation, there is less variation in operation methods between users (such as differences in the amount sprayed due to how the spray button is pressed or how long it is pressed), which has the advantage of less variation in effectiveness.

As an example of such a metered-dose aerosol, Patent Document 1 discloses a pest control aerosol equipped with a metered-dose aerosol valve that sprays 0.35 to 0.9 mL per spray.

Japanese Patent Application Publication No. 2010-280633

Although metered-dose aerosols for use in the air, such as insecticide aerosols and fragrance aerosols, have the advantage of little variation in effectiveness as described above, if the amount sprayed per time is small, the user does not feel fully satisfied with the use, and even though an effective amount of the agent is ejected in one spray, multiple sprays can result in excessive consumption. Furthermore, conventional metered-dose aerosols have a limit to the duration of the agent's effectiveness, and in order to maintain this effect, the spraying operation must be repeated after a certain time has passed since the spray, which must be done frequently.
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.

After extensive research, the inventors discovered that a metered-dose aerosol capable of spraying large volumes of 1.0 mL or more would increase the amount of medication ejected per spray, improving the feel of use while also increasing the amount of medication ejected; furthermore, they discovered that with a metered-dose aerosol that sprays large volumes, the duration of the medication's effectiveness varies depending on the spray duration of a single spray, and that there is an optimal balance between the amount of aerosol composition ejected per spray and the spray duration for sustaining the medication's effectiveness.

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, the aerosol composition comprising a concentrate containing a drug and a propellant, and filled in a pressure-resistant container, the 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), 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), 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), 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/sterilizing 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 drug-containing concentrate and a propellant, and the spray amount per 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, the method 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 metered-dose aerosol of the present invention, the aerosol composition can be sprayed in a large amount, in a predetermined amount ranging from 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. Furthermore, the efficacy of the drug can be improved and the effect of the drug can be sustained in a single 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 illustrating the test chamber used in Test Example 4.

Hereinafter, the embodiments of the present invention will be described in more 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 containing a drug concentrate and a propellant. Each component is described below.

(undiluted solution)
The concentrate constituting the aerosol composition of the present invention contains at least a chemical agent as an active ingredient. The active ingredient refers to 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/sterilizing ingredients, etc.

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, hiba 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. 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 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.

Aromatic components are components that emit a fragrance. In addition to the essential oil components mentioned above, examples of aromatic components include 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.

Deodorizing ingredients are components that can eliminate odors. Examples of deodorizing ingredients 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 fragrance components. These may be used alone or in combination of two or more.

The disinfecting/sterilizing ingredient is an ingredient that removes or kills microorganisms, mold, and bacteria. Examples of disinfecting/sterilizing ingredients 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 ingredients that have different effects. For example, a pest control ingredient can be used in combination with a fragrance ingredient, or a fragrance ingredient can be used in combination with a deodorizing ingredient other than a fragrance ingredient.

The content of the chemical agent in the concentrate is preferably 0.01 to 70% by mass/volume. A chemical agent content of 0.01% by mass/volume or more in the concentrate will ensure sufficient chemical effect, while a content of 70% by mass/volume or less will improve productivity. The lower limit of the chemical agent 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, while 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.

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 8 to 16 carbon atoms, such as Neo Thiosol manufactured by Chuo Kasei Co., Ltd. and Normal Paraffin MA manufactured by JXTG Nippon Oil & Energy Corporation. Typical isoparaffins have 8 to 16 carbon atoms, 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.

The solvent content in the concentrate is preferably 30 to 99.99% by mass/volume. Having a solvent content of 30% by mass/volume or more in the concentrate can improve productivity, while a content of 99.99% by mass/volume or less is preferred as 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.

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, and solubilizing agents.

The amount of concentrate contained 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. A concentration of 1% or more by volume of concentrate in the aerosol composition ensures sufficient efficacy of the agent, while a concentration of 50% or less by volume allows the concentrate to 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 preferably 3% by volume or more, and even more preferably 5% by volume or more. The upper limit is preferably 40% by volume or less, and 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.
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.

The propellant content 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 effects more likely to last. Furthermore, when the propellant content is 99% by volume or less, sufficient drug effects can be achieved. The propellant content in the aerosol composition preferably has a lower limit of 60% by volume or more, more preferably 70% by volume or more, and an upper limit of 97% by volume or less, even more preferably 95% by volume or less.

The volume ratio of concentrate to 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 maintaining such a volume ratio, sufficient drug efficacy can be achieved.

(metered dose 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.

Metered-dose aerosols are aerosols that spray a fixed amount of aerosol composition with a single spray operation. When the user operates the spray member (hereinafter also referred to as the spray button) attached to the aerosol valve, a fixed amount of the aerosol composition (concentrate and propellant) in the pressure-resistant container is sprayed through the aerosol valve, and the concentrate is converted into particles by the propellant and sprayed as spray particles.

(aerosol valve)
The aerosol valve comprises an opening/closing member for switching communication between the inside and outside of the pressure-resistant container and the outside when the spray member is operated 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 (spraying state) and blocking (non-spraying 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.

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 with 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 large amounts of medication. The spray volume of the aerosol valve can be appropriately set as long as it is within the above range.

(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 portion 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.

From the perspective of achieving the desired spray time range, the inner diameter of the nozzle of the spray button (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)
As described above, the metered dose aerosol of the present invention is prepared by filling a pressure-resistant aerosol container with the concentrate and propellant, i.e., the 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 on its side 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 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.

In the present invention, methods for adjusting the spray time for a single 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.

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.

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

<Test Example 1: Insecticidal efficacy confirmation test against Culex pipiens mosquito>
1. Preparation of Stock Solutions According to the formulations 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 (single injection amount 1.0 mL, stem hole area 1.4 mm ² ). Subsequently, 187.2 mL of liquefied petroleum gas (0.49 MPa (25°C)) 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 16 mg of transfluthrin.

Example 2
A metered dose aerosol with a spray amount of 1.0 mL per push and a discharge amount 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 0.6 mm.

(Comparative Example 1)
A metered dose aerosol with a spray amount of 1.0 mL per push and a discharge amount 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 0.4 mm.

Example 3
A metered-dose aerosol with a spray volume of 1.0 mL per push and an ejection amount 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 ^single spray volume of 1.0 mL and a stem hole area of 0.5 mm2.

Example 4
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 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 2)
A metered-dose aerosol with a spray volume of 1.0 mL per push and an ejection amount 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 ^single 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 (single injection amount 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 spray aerosol with a spray volume of 2.2 mL per push and an ejection volume of 16 mg of transfluthrin.

(Comparative Example 3)
A metered dose aerosol with a spray volume of 2.2 mL per push and a transfluthrin ejection volume of 16 mg 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 0.6 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 (single injection amount 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 spray aerosol with a spray volume of 0.2 mL per push and an ejection amount of 16 mg of transfluthrin.

(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 0.23 mm.

3. Measurement of Spray Time A laser diffraction particle size analyzer (Microtrac Bell Corporation, "LDSA-1400A") was placed 5 cm in a straight line in the spray direction (horizontal direction) from the nozzle of the constant-dose aerosol, so that the laser light was irradiated perpendicular to the spray direction. The spray button was pressed 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 increments. Note that interruptions in the laser light illumination of 0.05 seconds or less were considered continuous, and the measurement was terminated when the laser light did not illuminate 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 25 cm long x 25 cm wide 16-mesh cage 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 at 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, ^an 8-tatami room (volume 31.1 m3). 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 pallens was knocked down (it fell over and became immobile) was measured, and KT50 (minutes) (the time required for 50% of the Culex pipiens pallens) was calculated using 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 25 cm long x 25 cm wide 16-mesh cage 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 metered-dose aerosol was operated once (one push) at a height of 1 m from the floor in corner B of test chamber 10 (an 8-tatami room, 31.1 ^m3 capacity), and aimed at center A at a 45-degree angle. 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.

As shown in Table 3, immediately after spraying, the average KT50 was approximately 3 minutes for all metered dose aerosols. In contrast, as shown in Table 4, differences were observed in the average KT50 3 hours after spraying. Examples 1-4 and Comparative Examples 1-2 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 KT50s than Comparative Example 1, and Examples 3 and 4 had significantly shorter average KT50s 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 KT50s than Comparative Example 3. Comparative Examples 4-5 are examples in which the spray volume 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 varies depending on the spray duration.

<Test Example 2: Insecticidal Efficacy Test Against Cockroaches>
1. Preparation of Stock Solution 0.5 g of imiprothrin and 10 g of isopropyl myristate were weighed 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 4.

2. Preparation of Metered-Dose Aerosols According to Table 5, metered-dose aerosols of Examples 6 to 9 and Comparative Examples 6 and 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 (single injection amount 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 amount of 1.2 mg of imiprothrin.

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 0.6 mm.

(Comparative Example 6)
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 0.4 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 per push 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 an ejection amount of 1.2 mg of imiprothrin per push 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 an ejection amount of 1.2 mg of imiprothrin per push 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 metered 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 interior 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 climbing up. A mark was made on the filter paper 1 in the test area, close to the inner side wall of the 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 the Smoky brown cockroach 5 reached target point 3, the spray button of the metered-dose aerosol sprayer 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 unable to move) was measured. The test was performed three times, and the average was calculated. The results are shown in Table 6.

Examples 6-7 and Comparative Example 6 are examples in which the nozzle hole diameter of the spray button was changed for a metered dose aerosol with a spray volume of 1 mL per push, while Examples 8-9 and Comparative Example 7 are examples in which the area of the stem hole was changed. The results in Table 6 show that Examples 6 and 7, with spray times of 0.3 seconds and 0.73 seconds, 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, had significantly shorter knockdown times for Smoky Brown cockroaches than Comparative Example 7, with 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 weighed 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 can (volume 294 mL) was filled with 40 mL of concentrate 5 and closed with an aerosol valve (single injection amount 1.0 mL, stem hole area 1.4 mm ² ). Subsequently, 160 mL of liquefied petroleum gas (0.29 MPa (25°C)) was 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.

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.

(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.

3. Measurement of spray 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.

4. Insecticidal efficacy test against houseflies One female housefly was released as a test insect into a test room with an 8-tatami mat room (volume 31.1 ^m3 ). When the housefly landed on the wall, the spray button of the metered-volume aerosol sprayer was operated once (one push) toward 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.

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 to the solution to make up to 100 mL, thereby preparing 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 (single injection amount 1.0 mL, stem hole area 1.4 mm ² ). Subsequently, 160 mL of liquefied petroleum gas (0.29 MPa (25°C)) as a propellant was filled under pressure.
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 1.0 mg of linalool.

(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 a linalool ejection volume of 1.0 mg.

3. Measurement of spray 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.

4. Aroma sensory test (sensory evaluation 10 seconds after spraying)
As shown in Figure 3, the spray button of the metered-volume aerosol was operated once (pushed ^once ) from a height of 100 cm above the floor at the center position F of the first wall 21 of a test room 20 (a 6-tatami room, volume 25 m3), toward the third wall 23 opposite the first wall 21, approximately horizontally to the floor. Ten seconds after spraying, participants stood at the spray position, center position F of the first wall 21, center position G of the second wall 22 perpendicular to the first wall 21, and center position H of the third wall 23 opposite the first wall 21, and evaluated the fragrance intensity according to the evaluation criteria of the 6-level odor intensity rating system. The test was performed three times, and the average value was rounded off to obtain a 6-level 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 barely be detected (detection threshold concentration)
2: A 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 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 1/6. 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, has superior fragrance spread and intensity after 30 minutes compared to Comparative Example 9, which has an injection time of 1.35 seconds, and also has superior 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 bring the total volume to 100 mL, thereby preparing stock solution 7.

2. Preparation of a metered 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 (single injection amount 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.
A spray button (with a nozzle hole diameter of 1.6 mm) was attached to the aerosol valve, and a metered-dose aerosol was obtained with a spray 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 metered dose aerosol was measured in the same manner as in Test Example 1. The results are shown in Table 11.

4. Efficacy confirmation test Bathrooms in 10 ordinary homes 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 occurs were then selected. The spray button on a metered-dose aerosol sprayer was operated once (one push) toward one of the locations, and the treated location was designated the treated area. The other location was left untreated, and the area designated the untreated area. For each home, 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.

The results in Table 11 show that pink slime or black mold developed within one week in the untreated area, whereas the area treated with the metered-dose aerosol of Example 13 achieved sterilization and antifungal effects 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 corners F to H center position

Claims (7)

A metered-amount aerosol that sprays a fixed amount of the aerosol composition in one spray operation,
the aerosol composition comprises a concentrate containing at least one chemical selected from the group consisting of fragrance components and deodorizing components, and a propellant, and is filled in a pressure-resistant container;
The metered dose aerosol has a single spray volume of 1.0 to 2.2 mL and a single spray duration of 0.27 to 0.74 seconds. The metered dose aerosol according to claim 1, wherein the concentrate further contains a solvent. The metered dose aerosol according to claim 1 or 2, wherein the content of the drug in the concentrate is 0.01 to 70% by mass/volume. The metered dose aerosol according to any one of claims 1 to 3, wherein the volume ratio of the concentrate to the propellant in the aerosol composition is 1:99 to 50:50. A method for spraying a metered-volume aerosol, comprising filling a pressure-resistant container with an aerosol composition comprising a concentrate containing at least one chemical selected from the group consisting of fragrance components and deodorizing components, and a propellant, and spraying the aerosol composition using a metered-volume aerosol that is sprayed in a single spray operation in an amount of 1.0 to 2.2 mL and for a spray time of 0.27 to 0.74 seconds. A method for spraying a metered-volume aerosol, comprising filling a pressure-resistant container with an aerosol composition comprising a concentrate containing a pest control ingredient and a propellant, and spraying the aerosol composition using a metered-volume aerosol that sprays in an amount of 1.0 to 2.2 mL per spray operation for a spray time of 0.27 to 0.74 seconds (excluding cases where the aerosol is used against flying pests as target pests). A method for improving the durability of the effect of an agent in an aerosol composition sprayed using a metered aerosol, the aerosol composition comprising a concentrate containing at least one agent selected from the group consisting of fragrance components and deodorant components, and a propellant, the method comprising:
A method for improving the duration of efficacy of a drug by spraying the aerosol composition using a metered-dose aerosol that sprays a fixed amount of the aerosol composition in the range of 1.0 to 2.2 mL in 0.27 to 0.74 seconds.