JPH0120131B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an aerosol type anti-inflammatory analgesic agent that is comfortable to use and can be sprayed in its entirety in any usage mode, such as standing upright or inverted.

Various non-foaming aerosol products have been provided on the market, but they are required to satisfy the following conditions.

(1) Slightly flammable or higher is defined as having an explosive concentration of 0.25 g or less per 1 in the explosive and flammability test based on the Ministry of International Trade and Industry Notification No. 557. (2) It must be able to be sprayed in the form of a fine mist. (3) It must be safe to use when normally used on the human body. Ai, it does not foam on the skin and dries easily (4) It is inexpensive (5) It does not use gases that may cause environmental damage (6) It does not use chlorinated solvents (7) Dissolution of active ingredients Although products that satisfy these conditions have been developed, in the field of anti-inflammatory analgesics to which the present invention relates, (8) The product must be able to be injected in its entirety in any form of use, such as standing upright or upside down. (9) Since it is used for the human body, it is necessary to solve conditions such as excellent usability, that is, excellent adhesion, dryness, absorbency, and little cold sensation.
In order to satisfy condition (8), it is sufficient to mix a large amount of propellant with conventional anti-inflammatory and analgesic ingredients, but using nonflammable gas such as Freon as the propellant becomes expensive and requires (4) and (5). If the conditions are not met and cheap flammable gases such as dimethyl ether or liquefied petroleum gas are used, the gas will not pass the mildly flammable test (1), and if a large amount of water, etc. is added to pass the mildly flammable test in (1). No material has been found that satisfies all nine conditions, such as poor solubility and usability (7) and (9).

The present inventors have conducted various studies to develop an aerosol-type anti-inflammatory analgesic that satisfies all of the above nine conditions, and have found that the active ingredients of certain anti-inflammatory analgesics are The present invention was completed based on the discovery that it has the effect of lowering the explosive concentration.

That is, in the present invention, dimethyl ether 10 to 30%
(wt%, same below) and pressure at 20℃
A propellant consisting of 6-15% of liquefied petroleum gas with a weight of 0.8-8.0 Kg/cm ² and the balance consisting of 10-30 parts (by weight) of the main active ingredient consisting of at least three of camphor, menthol, methyl salicylate and glycol salicylate. The present invention relates to an aerosol type anti-inflammatory analgesic agent comprising a stock solution consisting of 35 to 45 parts of an alcohol component consisting of at least one type of _C1 to _C3 alcohol and 25 to 45 parts of water.

The aerosol-type anti-inflammatory analgesic agent of the present invention has an excellent feeling of use and can be injected in its entirety in any form of use, such as standing upright or inverted, and the injected anti-inflammatory analgesic agent passes the test of being sufficiently mildly flammable.

The blending ratio of dimethyl ether and liquefied petroleum gas in the propellant is the one per eerosol container, while the blending ratio of the main active ingredient, alcohol component, and water in the stock solution is the ratio that constitutes 100 parts of the stock solution.

In the present invention, it is essential to use 10 to 30 parts of the main active ingredient consisting of at least three of camphor, menthol, methyl salicylate, and glycol salicylate as a component of the stock solution.
The main active ingredient has the effect of increasing the explosive concentration, which is thought to be due to its interaction with the propellant. For example, when used in an inverted position, the liquefied petroleum gas that can be injected in its entirety can be heated to a level above slightly flammable ( pass). The mechanism of increasing the explosive concentration is still not fully understood, but it may be that the propellant remains in the spray particles of the main active ingredient for a longer time, which prevents it from exploding to a higher concentration than the theoretical explosive concentration. I think so.

If two or more of the above-mentioned main active ingredients are missing, the feeling of use and medicinal efficacy will be inferior, and the above-mentioned explosive concentration raising effect will be lost, and if you are trying to obtain a product that can be injected in its entirety in any form of use. In some cases, it is difficult to pass the grade of mild flammability or higher.

The amount of the main active ingredients in the present invention is 10 to 30 parts as described above, and camphor/menthol/methyl salicylate/glycol salicylate is 20 to 30 parts.
Preferably, the ratio is 40/20 to 40/15 to 35/5 to 25 (weight ratio). If it is less than 10 parts, the feeling of use and medicinal efficacy will be poor, the above-mentioned explosive concentration raising effect will be lost, and it will be difficult to pass the mildly flammable or higher level, and if it is more than 30 parts, it will be inferior. It is difficult to dissolve the stock solution.

The alcohol component consisting of at least one type of _C1 to _C3 alcohol is a necessary component as a solvent for the main active ingredient and to improve the feeling of use.
~45 copies used. Examples of C ₁ to _{C 3} alcohols include methanol, ethanol, propanol, and isopropanol, and any of them can be used, and denatured ethanol can also be used. If the amount is less than 35 parts, drying on the skin will be slow and stickiness will remain, impairing the feeling of use, and if it is more than 45 parts, it will be difficult to pass the grade of mild flammability or higher.

Water is used to pass mild flammability or higher, and 25 to 45 parts of water is used as a component of the stock solution. When the amount is less than 25 parts, it is difficult to pass the level of mild flammability, and when it is more than 45 parts, drying on the skin is delayed, impairing the feeling of use.

If necessary, a total of 30 parts or less of other components may be added to the stock solution of the present invention. Other ingredients include, for example, ordinary anti-inflammatory and analgesic agents, powders, surfactants, hydrophilic solvents, etc. other than the main active ingredient.

Examples of the usual anti-inflammatory analgesics include diphenhydramine, benzyl nicotinic acid ester, squalane, etc., and depending on the balance with other ingredients, 30 parts or less, preferably about 10 parts may be used. However, if there are more than 30 copies, the usability will be poor.

The powder may contain up to 30 parts, preferably up to 20 parts, of a material with excellent redispersibility as a component of the stock solution in order to suppress combustibility and prevent stickiness on the skin. Many cannot be used because they cause clogging.
Examples of powders that can be used include talc, zinc stearate, zinc white, and silicic anhydride.

In some cases, surfactants may help the adhesion or adsorption of active ingredients to the skin, and in such cases, 10 parts or less may be used as a component of the stock solution, but if the amount is large, may cause foaming and dryness on the skin. Examples of these include fatty acid esters, ionic surfactants, nonionic surfactants, and the like.

As a hydrophilic solvent, one having the function of dissolving the active ingredient is used as a component of the stock solution in an amount of 10 parts or less. Examples of these include ketones, esters, alcohols with C4 or _higher , and in particular those with low boiling points such as acetone for ketones, ethyl acetate for esters, and butanol for alcohols with _C4 or higher. preferable. However, since they are more irritating to the skin than C ₁ -C ₃ alcohols and have a unique fragrance, it is necessary to keep the amount of them blended to a minimum that allows the active ingredients to dissolve.

The other ingredients listed should not exceed 30 parts in the concentrate composition. If it exceeds 30 parts, the proportion of the essential components becomes relatively small, resulting in poor usability and unsatisfactory combustibility or total injection performance.

As mentioned above, the propellant used in the present invention is dimethyl ether and a pressure of 0.8 to 8.0 at 20°C.
Kg/cm ² of liquefied petroleum gas.

Dimethyl ether is used to improve the mist condition during spraying and to spray the entire amount, and is used in an amount of 10 to 30% per aerosol container. Ten
If it is less than 30%, the mist will be poor if the stock solution of the present invention is water/alcohol/active ingredient or other system, and if it is more than 30%, it may not pass the mildly flammable level or higher. Have difficulty.

Liquefied petroleum gas is used to obtain the necessary internal pressure to be able to inject the entire amount no matter how it is used, and 6 to 15% is required per aerosol container. If it is less than 6%, it will not be possible to inject the full amount when used upside down, and if it is more than 15%, it will be difficult to pass the grade of mild flammability or better.

Conventionally, it was thought that the content of liquefied petroleum gas must be 5% or less in order to pass the mild flammability test without reducing the feeling of use. The reason why it is able to pass the mildly flammable or higher level without impairing the feeling of use is due to the action of increasing the explosive concentration, which is thought to be due to the interaction with the main active ingredient, which is one of the components of the stock solution, as mentioned above. Conceivable.

When filling the aerosol type anti-inflammatory analgesic agent of the present invention into an aerosol container, there is no particular restriction on the filling method. For example, each component of the stock solution may be placed individually and a propellant may be press-fitted, or each component of the stock solution may be filled with a propellant. After mixing and adjusting, the propellant may be press-injected. Further, a part of the components of the stock solution may be press-injected together with the propellant. Regarding the injection of the propellant, dimethyl ether and liquefied petroleum gas may be injected separately, or a mixture may be injected.

The aerosol container used for filling the aerosol-type anti-inflammatory and analgesic agent of the present invention does not require any special structure, and a ready-made eyasol container can be used.

Next, the aerosol type anti-inflammatory analgesic agent of the present invention will be explained with reference to Examples and Comparative Examples.

Example 1 An aerosol type anti-inflammatory analgesic agent having the composition shown below was prepared.

(Composition) (Parts by weight) Camphor 4.5 Menthol 4.5 Methyl salicylate 3.5 Glycol salicylate 2.0 99% geraniol-denatured ethanol 34.2 Purified water 28.3 Dimethyl ether 14.0 Liquefied petroleum gas (pressure 1.8 Kg/cm ² at 20°C) 9.0 Filling the eyasol container: First, camphor, menthol, methyl salicylate, and glycol salicylate were dissolved in 99% geraniol-denatured ethanol, and then purified water was added to prepare a stock solution, which was filled into an aerosol container with a stem pore diameter of 0.3 mmφ.
Housing hole diameter 0.6mmφ, vapor tap diameter 0.4mm
This was done by installing a φ valve, then pressurizing a mixture of dimethyl ether and liquefied petroleum gas as a propellant, and then installing a button with a mechanical break-up with a hole diameter of 0.4 mmφ.

The obtained aerosol type anti-inflammatory analgesic of the present invention is as follows:
It was possible to inject the full amount in any usage mode, including upright or inverted. In addition, the injected anti-inflammatory analgesic passed the mildly flammable or higher level, had little feeling of use, that is, a cold sensation, and was well absorbed, so it had excellent fast-acting properties.

Example 2 An aerosol type anti-inflammatory analgesic agent having the following composition was prepared.

(Composition) (Parts by weight) Camphor 4.5 Menthol 4.0 Methyl salicylate 4.0 Glycol salicylate 2.0 99% ethanol 30.0 Purified water 26.5 Talc 4.0 Dimethyl ether 13.0 Liquefied petroleum gas (pressure 1.2 Kg/cm ² at 20°C) 12.0 Filling the eyasol container: First, camphor, menthol, methyl salicylate, and glycol salicylate were dissolved in 99% ethanol, purified water was added to this, and the mixture was filled into an aerosol container.Then, talc was added to prepare a stock solution, and dimethyl ether and liquefied petroleum were added as propellants. After pressurizing the mixture with gas, the stem hole diameter is 0.4mmφ and the housing hole diameter is
This was done by installing a valve with a diameter of 0.55 mmφ and a vapor tap diameter of 0.3 mmφ, and then a button with a mechanical break-up with a hole diameter of 0.3 mmφ.

The obtained aerosol type anti-inflammatory analgesic of the present invention is,
It was possible to inject the full amount in any usage mode, including upright or inverted. Furthermore, the injected anti-inflammatory analgesic passed the test of being mildly flammable or better, and had an excellent usability.

Example 3 An aerosol type anti-inflammatory analgesic agent having the composition shown below was prepared.

(Composition) (Parts by weight) Camphor 4.5 Menthol 4.5 Methyl salicylate 3.5 Diphenhydramine 0.4 Nicotinic acid benzyl ester 0.03 Acetone 6.01 Purified water 24.06 99% cyclose-denatured ethanol 25.0 Dimethyl ether 25.0 Liquefied petroleum gas (pressure 7.0Kg/cm ² at 20℃) ) 7.0 To fill an aerosol container, first prepare a stock solution by dissolving camphor, menthol, methyl salicylate, diphenhydramine, and benzyl nicotinic acid ester in 99% cyclose denatured ethanol and acetone, then adding purified water. After filling the aerosol container, the stem hole diameter is 0.33mm.
φ, housing hole diameter 0.64mmφ, vapor tap diameter
Attach a 0.41mmφ valve, pressurize dimethyl ether, then pressurize liquefied petroleum gas, then adjust the hole diameter.
This was done by installing a 0.41mmφ button with a mechanical break-up.

The obtained aerosol type anti-inflammatory analgesic of the present invention is as follows:
It was possible to inject the full amount in any usage mode, including upright or inverted. In addition, the injected anti-inflammatory analgesic was found to be mildly flammable or better, and had an excellent usability.

Example 4 An aerosol type anti-inflammatory analgesic agent having the composition shown below was prepared.

(Composition) (Parts by weight) Camphor 3.5 Menthol 3.5 Methyl salicylate 7.5 Glycol salicylate 6.0 Surfactant (trade name: Calibon L-400, manufactured by Sanyo Chemical Industries, Ltd.) 1.0 Isopropanol 27.0 Purified water 24.5 Zinc white 4.0 Dimethyl ether 14.0 Liquefied petroleum gas (Pressure: 4.0 Kg/cm ² at 20°C) 9.0 To fill an aerosol container, first, camphor, menthol, methyl salicylate, and glycol salicylate were dissolved in isopropanol along with a surfactant, then purified water was added and the mixture was filled into an eyasol container. Later, zinc white was added and the stem hole diameter was 0.4.
This was done by installing a valve with a housing hole diameter of 0.6 mmφ, a vapor tap diameter of 0.3 mmφ, and a button with a mechanical break-up with a hole diameter of 0.4 mmφ, and then pressurizing a mixture of dimethyl ether and liquefied petroleum gas.

The obtained aerosol type anti-inflammatory analgesic of the present invention is as follows:
It was possible to inject the full amount in any usage mode, including upright or inverted. Furthermore, the injected anti-inflammatory analgesic passed the test of being mildly flammable or better, and had an excellent usability.

Comparative Example 1 A comparative aerosol-type anti-inflammatory analgesic was prepared in the same manner as in Example 1, except that the composition of the aerosol-type anti-inflammatory analgesic was 5.5 parts by weight of liquefied petroleum gas and 17.5 parts by weight of dimethyl ether. It was filled into an aerosol container in the same manner as above.

The resulting aerosol type anti-inflammatory analgesic could not be sprayed in its entirety when used in an inverted position.

Comparative Example 2 A comparative aerosol type anti-inflammatory analgesic was prepared in the same manner as in Example 3 except that methyl salicylate was not used and 27.56 parts by weight of purified water was used. It was filled into an aerosol container in the same manner as above.

The obtained aerosol type anti-inflammatory analgesic could be injected in its entirety even when used in an inverted position, but the injected anti-inflammatory analgesic did not pass the test as more than slightly flammable.

Claims (1)

[Scope of Claims] 1. A propellant consisting of 10 to 30% by weight of dimethyl ether and 6 to 15% by weight of liquefied petroleum gas having a pressure of 0.8 to 8.0 Kg/cm ² at 20°C, and the balance being camphor, menthol, and methyl salicylate. and 10 to 30 parts by weight of the main active ingredient consisting of at least three types of glycol salicylate, and 35 to 45 parts by weight of an alcohol component consisting of at least one type of _C1 to _C3 alcohol.
An aerosol-type anti-inflammatory analgesic consisting of parts by weight and a stock solution consisting of 25 to 45 parts by weight of water. 2. Claims No. 2 in which the stock solution further contains 30 parts by weight or less of one or more of anti-inflammatory analgesics, powders, surfactants, and hydrophilic solvents other than the main active ingredient. The aerosol type anti-inflammatory analgesic agent according to item 1.