JPH08175982A - 4-biphenylyl acetate composition - Google Patents

Abstract

PURPOSE: To provide a new composition giving a foaming aerosol antiphlogistic painkiller having excellent stability of active principle and containing 4- biphenylyl acetate, a base, a lower alcohol and water at a specific ratio. CONSTITUTION: The objective composition contains (A) 1-5wt.% (preferably 2-3wt.%) 4-biphenylyl acetate, (B) 0.3-10wt.% (preferably 0.5-7wt.%) a base comprising (di)ethanolamine, diisopropanolamine, triethanolamine or 2- amino-2-(hydroxymethyl)-propane-1,3-diol, etc., (C) 10-50wt.% (preferably 20-40wt.%) a lower alcohol comprising methanol, ethanol and (iso)propanol and (D) 40-80wt.% (preferably 50-70wt.%) and its pH is at 6.5-8.0 (preferably 7.0-8.0).

Description

Detailed Description of the Invention

[0001]

The present invention relates to a novel 4-biphenylylacetic acid composition liquid, namely 4-biphenylylacetic acid (hereinafter referred to as
It may be abbreviated as BPAA. ) Containing an anti-inflammatory analgesic undiluted solution, more specifically, it becomes a foam when sprayed as an aerosol agent and self-defoams without breaking, facilitating the active ingredient of the main ingredient: 4-biphenylylacetic acid. To produce a foamable aerosol anti-inflammatory analgesic with excellent skin penetration of the main drug, a strong anti-inflammatory and analgesic effect, less side effects on the skin, and excellent stability of the active ingredient. Concerning the required aerosol concentrate. Further, the present invention is not limited to the production of a foamable aerosol anti-inflammatory analgesic, but also to a 4-biphenylylacetic acid composition liquid, which is an anti-inflammatory analgesic undiluted solution necessary for the production of an aerosol agent such as a spray type aerosol agent and a gel aerosol agent. Concerned.

[0002]

2. Description of the Related Art As a prior art of an aerosol formulation containing an anti-inflammatory analgesic as an active ingredient, Japanese Patent Publication No. 52-210
51, JP 61-83117, and JP 6
Many reports have been made such as 3-264522, JP-A-3-209315, and JP-A-3-72433. Among them, an aerosol preparation containing an anti-inflammatory analgesic such as methyl salicylate and glycol salicylate as an active ingredient and a local stimulant such as l-menthol, dl-camphor, benzyl nicotinate, and capsacin is already on the market. Also, JP-A-63-119
In Japanese Patent Publication No. 420, a foamed aerosol anti-inflammatory analgesic containing a non-steroidal acidic anti-inflammatory analgesic for the purpose of cracking the formed foam is proposed.

However, the conventional aerosol composition sprayed in the form of a mist often causes the anti-inflammatory and analgesic agent, which is the active ingredient, to be scattered and adhered to other than the intended skin, which may stimulate the nasal mucosa and cause coughing. is there. Further, an aerosol composition which is sprayed in the form of foam generally has fine bubbles in many cases and has a drawback that it is difficult to defoam by itself. As a typical example of an aerosol composition which is sprayed in the form of foam, those described in JP-A-2-255889 are known, but since the evaporation of the propellant takes time, the defoaming property is If the formed foam is not rubbed sufficiently, the foam may not be completely broken and uniform coating may not be possible.

On the other hand, the non-steroidal anti-inflammatory drug has a strong anti-inflammatory effect and is widely used as an orally-administered preparation in the field of orthopedic surgery, and a preparation for external use for the purpose of reducing side effects on the digestive tract and the like. Is proposed. However, this acidic anti-inflammatory analgesic is used as an aerosol,
When sprayed, fine bubbles, which are aerosols, scatter and stimulate the nasal mucosa, which may cause coughing and, in severe cases, asthma, which is a problematic formulation.

By the way, among the non-steroidal anti-inflammatory and analgesic agents, 4-biphenylylacetic acid is known as a compound having a strong anti-inflammatory and analgesic action, but when this is orally administered, side effects such as gastrointestinal disorders are caused. Therefore, percutaneously absorbable preparations such as gel ointment, lotion, and poultice, which are locally percutaneously absorbed, have been proposed and have been widely used in actual therapeutic fields. Even when this BPAA having an excellent anti-inflammatory and analgesic effect is used as an aerosol agent, there are the above-mentioned formulation problems. Thus far, an actual formulation study has been conducted on an aerosol agent containing BPAA as an active ingredient. I didn't. In particular, BPAA is insoluble or sparingly soluble in various pharmaceutically acceptable solvents such as water, alcohol, propylene glycol, etc., and thus has not been able to produce an aerosol agent having good skin penetration.

[0006]

DISCLOSURE OF THE INVENTION The present invention has been made in view of the above-mentioned prior art, and in particular, when it is jetted, it becomes a foamy form, and it defoams itself without breaking, and the active ingredient It is an object of the present invention to provide an undiluted aerosol solution for producing an aerosol anti-inflammatory analgesic composition which can easily and uniformly apply a certain 4-biphenylylacetic acid and can give a refreshing feeling by the heat of vaporization of a propellant.

[0007]

In order to solve the above problems, the present invention provides at least the following formulation: 4-biphenylylacetic acid 1-5% by weight, base 0.3-10% by weight, lower alcohol 10-50. % -Water, 40-80% by weight, and its pH is within the range of 6.5-8.0, that is, 4-biphenylylacetic acid composition liquid, that is, anti-flame containing 4-biphenylylacetic acid. To provide an undiluted solution of an analgesic aerosol.

The anti-inflammatory analgesic aerosol stock solution of the present invention is suitable for ensuring that the BPAA contained therein is completely dissolved in the stock solution of aerosol, especially when 4-biphenylylacetic acid is used as the stock solution of aerosol as described above. A base, further containing a specific amount of lower alcohol and water, and having a pH in the range of 6.5 to 8.0; at least 4-biphenylylacetic acid: 1 to 5% by weight, Base: 0.3 to 10% by weight, lower alcohol: 10
˜50% by weight and water: 40-80% by weight.

[0009]

The content of 4-biphenylylacetic acid, which is the active ingredient in the anti-inflammatory analgesic aerosol stock solution of the present invention, in the aerosol stock solution is the amount by which the anti-inflammatory analgesic effect of the aerosol agent produced using the stock solution is sufficiently exerted. , That is, 1
-5% by weight, preferably 2-3% by weight.
When the content of the active ingredient is less than 1% by weight, a sufficient anti-inflammatory and analgesic effect is not exhibited, and when it exceeds 5% by weight, side effects are likely to occur and the object of the present invention tends to be difficult to achieve. There is.

The aerosol stock solution of the present invention contains a base necessary for ensuring that the 4-biphenylylacetic acid contained in the aerosol stock solution is uniformly solubilized in the stock solution. Examples of such bases include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; inorganic bases such as alkali metal carbonates and hydrogen carbonates such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate; Alternatively, mono (lower alkanol) amines such as monomethanolamine, monoethanolamine, monopropanolamine, and monoisopropanolamine; dimethanolamine, diethanolamine, dipropanolamine, diisopropanolamine, dibutanolamine, diisobutanolamine,
Di (lower alkanol) amines such as di-sec-butanolamine; tri (methanolamine, triethanolamine, tripropanolamine, triisopropanolamine, tributanolamine, triisobutanolamine, tri-sec-butanolamine, etc. Lower alkanol) amine; mono (lower alkyl) amine such as methylamine, ethylamine, propylamine, isopropylamine; di (lower alkyl) amine such as dimethylamine, diethylamine, dipropylamine, diisopropylamine; trimethylamine, triethylamine, tripropyl Tri (lower alkyl) amines such as amine and triisopropylamine; 2-amino-
2- (hydroxymethyl) -propane-1,3-diol) and the like. Among the above, organic bases such as mono-, di- or tri- (lower alkanol) amines are preferable, and diisopropanolamine and triethanolamine are particularly preferable. The content of the base generally varies depending on the type of amine to be blended and the amount of the main drug, but it is an amount that uniformly dissolves 4-biphenylylacetic acid, which is the active ingredient, in the aerosol concentrate, and the pH of the aerosol concentrate. The amount may be adjusted to 6.5 to 8.0, usually 0.3 to 10% by weight, and preferably 0.5 to 7% by weight.

The lower alcohol to be blended with the aerosol concentrate of the present invention is, in one aspect, a component having a property of imparting defoaming properties to the aerosol formulation when it is used as an aerosol anti-inflammatory analgesic. is there. Examples of such lower alcohols include ethanol, denatured ethanol, n-propanol, isopropanol,
C2-C4 alcohols such as n-butanol and isobutanol are preferred, and these can be used alone or in admixture of two or more. Among these lower alcohols, ethanol, denatured ethanol and isopropanol are particularly preferable in terms of versatility. The content of the lower alcohol in the stock solution is 10 in order to improve the defoaming property and the foaming property and to further stabilize the stock solution.
To 50% by weight, more preferably 20 to 50% by weight.
It is in the range of 40% by weight. That is, in order to secure the defoaming property, it is 10% by weight or more, preferably 20% by weight or more, and in order to secure the foaming property, it is 50% by weight or less, preferably 40% by weight or less. Turned out to be good.

The water to be added to the aerosol stock solution of the present invention is, in one aspect, a component having the property of imparting foamability to the foamable aerosol anti-inflammatory analgesic obtained using the stock solution. The type of the water component is not particularly limited, and for example, purified water or ion-exchanged water used for usual aerosol compositions can be preferably used. The blending amount in the undiluted solution is 40% by weight or more, preferably 50% by weight or more for improving the foaming property, and 80% by weight or less, preferably 70% by weight for improving the defoaming property. It turned out that it is better to set it to be less than or equal to%.

The anti-inflammatory analgesic aerosol stock solution of the present invention having the basic formulation described above has a pH of 6.5 to 5.
It is better to set it within the range of 8.0. In general, percutaneous absorption agents for external use (for example, ointment) are generally set to a weakly acidic pH close to the pH of the skin surface in order to promote percutaneous absorption of the main drug and avoid skin disorders. Is the B of the present invention
The PAA-containing aerosol anti-inflammatory analgesic is characterized in that it is within a pH range higher than that. Among them, the stock solution of the aerosol of the present invention has a pH of 7.0.
It was found that it is better to be in the range of ~ 8.0.

Therefore, in a preferred embodiment of the present invention, at least the following formulation: 4-biphenylylacetic acid 2-3% by weight, organic base 0.5-7% by weight, lower alcohol 20-40% by weight, water 50 ˜70 wt%, and its pH is in the range of 7.0 to 8.0.

The anti-inflammatory analgesic undiluted solution of the present invention comprises at least 4-biphenylylacetic acid: 1 to 5 as described above.
% By weight, base: 0.3 to 10% by weight, lower alcohol:
It is composed of 10 to 50% by weight and water: 40 to 80% by weight, and its pH is within the range of 6.5 to 8.0. An oil component and a surfactant can be blended as a blending component. The oil component as a component that can be further blended in the stock solution of the present invention is, for example, a component having a property of imparting antifoaming properties to the foamable aerosol anti-inflammatory analgesic obtained by using the stock solution.

Examples of such oil components are silicone oils such as chain dimethyl silicone oil (methyl polysiloxane), cyclic silicone oil, and methylphenyl silicone oil; Isopar A, Isopar C, Isopar D, Isopar E, Isopar G. , Isopar H, Isopar K, Isopar L, Isopar M (all manufactured by Exxon), isoparaffinic hydrocarbons such as liquid paraffin, hydrocarbons such as petrolatum, squalane, α-olefin oligomer and squalene; olive oil, almond oil, Jojoba oil, peanut oil, castor oil, palm oil, palm oil, safflower oil, sunflower oil, cottonseed oil,
Avocado oil, camellia oil, corn oil, wheat germ oil,
Vegetable oils such as rice bran oil, cacao oil, sesame oil, evening primrose oil, safflower oil, southern oil, soybean oil, rapeseed oil; lanolin,
Animal oils such as lanolin derivatives, turtle oil, mink oil, beeswax, pristane, egg yolk oil; butyl stearate,
Hexyl laurate, isopropyl myristate, octyldodecyl myristate, isopropyl myristate, diisopropyl adipate, diisopropyl sebacate and other fatty acid esters; 1-menthol, limonene, cineole, linalool, pinecane, essential oils such as camphor, natural and synthetic flavors, etc. These can be used alone or in admixture of two or more. Among them, 1-menthol is preferably blended in order to impart a fragrance as a product property to the aerosol anti-inflammatory analgesic obtained by using the stock solution of the present invention.

The content of these oil components in the stock solution is
In order to improve the defoaming property, it is 0.01% by weight or more, preferably 0.1% by weight or more, and in order to improve the foaming property and not to give stickiness during use,
It has been found that it is preferable to set it to 5% by weight or less, preferably 3% by weight or less.

The surfactant which can be blended in the stock solution of the present invention is, for example, a foaming aerosol anti-inflammatory analgesic obtained by using this stock solution to improve the compatibility between water and oil components. It is also a component used to improve foamability. Examples of such a surfactant include sorbitan fatty acid ester, glycerin fatty acid ester, decaglycerin fatty acid ester, polyglycerin fatty acid ester, propylene glycol / pentaerythritol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbitol fatty acid ester, Polyoxyethylene glycerin fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene alkyl ether (1), polyoxyethylene alkyl ether (2), polyoxyethylene phytosterol phytostanol, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene Alkyl phenyl ether, polyoxyethylene castor oil, hydrogenated castor oil, polyoxy Ethylene Lanolin Lanolin alcohol beeswax derivatives, polyoxyethylene alkylene alkyl amine fatty acid amides, polyoxyethylene alkyl phenyl formamide condensate,
Nonionic surfactants such as single chain length polyoxyethylene alkyl ethers; alkyl sulfates, polyoxyethylene alkyl ether sulfates, N-acyl amino acids and their salts, N-acyl methyl taurine salts, polyoxyethylene alkyl ether acetic acid Anionic surfactants such as salts, alkyl sulfone carboxylates, α-olefin sulfonates, alkyl phosphates and polyoxyethylene alkyl phosphates; cationic surfactants such as alkyl ammonium salts and alkyl benzyl ammonium salts And amphoteric surfactants such as betaine acetate, imidazolinium betaine, and lecithin. These surfactants can be used alone or in admixture of two or more. Among these surfactants, nonionic surfactants are particularly preferable in terms of reaction stability with an active ingredient, safety with little skin irritation, and corrosiveness with a metal container for aerosol. It can be used for.

The content of these surfactants in the undiluted solution is 0.1% by weight or more, preferably 0.3% by weight or more in order to improve the foaming property, and is not sticky when used. Furthermore, it has been found that the amount is preferably 5% by weight or less, and more preferably 3% by weight or less, so as not to irritate the skin.

As described above, the anti-inflammatory analgesic aerosol stock solution of the present invention contains the active ingredient 4-biphenylylacetic acid, a lower alcohol, a base, water, and optionally an oil component and a surfactant. In the present invention, it is possible to further contain other components.
Examples of such components include polyhydric alcohols such as ethylene glycol, diethylene glycol, triethylene glycol, propylene glycol, glycerin, and 1,3-butylene glycol in order to ensure moisturizing properties; preservatives such as parabens; dibutylhydroxyl. Antioxidants such as toluene; p such as ammonia water and citric acid
Thickeners such as carboxymethyl cellulose and carboxy vinyl polymer; zinc oxide, titanium oxide, magnesium oxide, precipitated calcium carbonate, heavy magnesium carbonate, magnesium silicate, kaolin, bentonite, nylon powder, talc, silicon powder, etc. The above powder and the like may be blended within a range that does not deviate from the object of the present invention.

Among them, in the anti-inflammatory analgesic aerosol stock solution of the present invention, for example, in order to secure the moisturizing effect of the foamable aerosol anti-inflammatory analgesic obtained using this stock solution, ethylene glycol, diethylene glycol, triethylene glycol, Propylene glycol, glycerin, 1,3
-Polyhydric alcohols such as butylene glycol, especially glycerin and 1,3-butylene glycol are preferably blended, and the blending amount thereof is 0.5 to 10% by weight, preferably 1 to 5% by weight. found. In addition, in the present invention, the emulsion stability of the anti-inflammatory analgesic is improved in the metal container for aerosol, and it plays the role of non-slip when rubbing the anti-inflammatory analgesic on the skin, and enhances the massage effect. Therefore, it is preferable to include powder such as talc,
The blending amount is 0.5 to 6% by weight, preferably 2 to 5
It has been found that weight percent is good.

In order to prepare an anti-inflammatory analgesic aerosol agent using the aerosol concentrate of the present invention, the aerosol container is filled in a usual manner by an aerosol manufacturing technique generally used in this technical field, and an aerosol valve is attached. Thus, products such as spray aerosols and gel aerosols can be manufactured. Among them, in order to prepare a foamable aerosol anti-inflammatory analgesic using the stock solution of the present invention, from the viewpoint of both foaming property and antifoaming property, (A) Stock solution for foamable aerosol anti-inflammatory drug of the present invention: 5
It has been found that it is preferable to be composed of 5 to 85% by weight, and (B) a propellant having a vapor pressure of ² to 7 kg / cm ² · G at 25 ° C .: 15 to 45% by weight.

As a propellant, a vapor pressure of 2 kg / 25 ° C.
If it is smaller than cm ² · G, the defoaming property is not sufficient, and if it exceeds 7 kg / cm ² · G, the pressure is high, which is not preferable in terms of safety. The vapor pressure is preferably 2 to 5 kg / cm ² · G at 25 ° C.

Typical examples of such propellants include, for example, LPG (propane, isobutane and n-
Liquefied gas such as liquefied petroleum gas containing butane as a main component, dimethyl ether, difluoromonochloroethane, monochlorodifluoromethane, tetrafluoroethane, and the like, and liquefied gases such as hydrocarbons are used alone or in combination of two or more. be able to. Among these propellants, from the viewpoint of improving the foaming property, the LP
G (liquefied petroleum gas) is preferred. In the present invention, the liquefied gas may be, for example, air, N ₂ , O ₂ or CO.
A compressed gas such as ₂ , N ₂ O or the like can be mixed.

When a foamable aerosol anti-inflammatory analgesic is prepared using the anti-inflammatory analgesic undiluted solution of the present invention, as described above, 55-85 wt% of the undiluted solution of the present invention and 15-45 wt% of the propellant are used. However, when the amount of the undiluted solution exceeds 85% by weight, that is, when the proportion of the propellant is less than 15% by weight, the defoaming property is deteriorated, and the undiluted solution is When the proportion of the propellant is less than 55% by weight, that is, when the proportion of the propellant exceeds 45% by weight, the foamability is lowered. Therefore, the proportion of the undiluted solution is 55% by weight or more, preferably 60% by weight or more and 85% by weight or less, preferably 80% by weight or less, and the proportion of the propellant is 15% by weight.
The above content is preferably 20% by weight or more and 45% by weight or less, preferably 40% by weight or less.

Among the anti-inflammatory analgesic aerosols thus obtained, the foamable aerosol anti-inflammatory analgesic becomes a foam when sprayed and self-defoams without breaking,
The active ingredient, 4-biphenylylacetic acid, can be applied uniformly, and a refreshing feeling can be imparted by the heat of vaporization of the propellant. This foamable aerosol anti-inflammatory analgesic was found to have an anti-inflammatory analgesic effect equivalent to that of a gel ointment of 4-biphenylylacetic acid known as a skin external preparation.

From the above description, the anti-inflammatory analgesic aerosol stock solution as a preferred embodiment of the present invention is the following formulation: 4-biphenylylacetic acid 1-5% by weight organic base 0.3-10% by weight lower alcohol 10 to 50% by weight Oil component 0.01 to 5% by weight Surfactant 0.1 to 5% by weight Powder 0.5 to 6% by weight Water 40 to 80% by weight Moisturizer 0.5 to 10% by weight, It will be appreciated that the anti-inflammatory analgesic aerosol stock solution has a pH in the range of 6.5-8.0.

Further, as a more preferred specific embodiment of the present invention, an anti-inflammatory analgesic aerosol stock solution is prepared by the following formulation: 4-biphenylylacetic acid 2-3% by weight organic base 0.5-7% by weight lower alcohol 20-40% by weight. Oil component 0.1 to 3% by weight Surfactant 0.3 to 3% by weight Powder 2 to 5% by weight Water 50 to 70% by weight Moisturizer 1 to 5% by weight, and its pH is 7.0 to 8. It will be understood that it is an anti-inflammatory analgesic aerosol stock solution in the range of 0, especially a foamable aerosol stock solution.

Therefore, as a preferred embodiment of the aerosol anti-inflammatory and analgesic agent using the preferred anti-inflammatory and analgesic aerosol stock solution of the present invention: (A) It has the following formulation and its pH is 6.5-6.5.
Aerosol stock solution in the range of 8.0: 55-85% by weight: 4-biphenylylacetic acid 1-5% by weight Organic base 0.3-10% by weight Lower alcohol 10-50% by weight Oil component 0.01-5% by weight % Surfactant 0.1 to 5% by weight Powder 0.5 to 6% by weight Water 40 to 80% by weight Moisturizer 0.5 to 10% by weight and (B) Vapor pressure 2 to 7 kg / cm at 25 ° C. It is an aerosol anti-inflammatory analgesic consisting of ² · G propellant: 15 to 45% by weight.

A more preferred embodiment of the foamable aerosol anti-inflammatory analgesic using the more preferred anti-inflammatory analgesic undiluted solution of the present invention is: (A) It comprises the following formulation and its pH is 7.0.
Aerosol stock solution in the range of 8.0: 60-80% by weight: 4-biphenylylacetic acid 2-3% by weight organic base 0.5-7% by weight lower alcohol 20-40% by weight oil component 0.1-3% by weight % Surfactant 0.3 to 3% by weight powder 2 to 5% by weight water 50 to 70% by weight moisturizing agent 1 to 5% by weight and (B) at a vapor pressure of 25 ° C. of ² to 7 kg / cm ² · G A propellant: 20 to 40% by weight of a foamable aerosol anti-inflammatory analgesic.

The anti-inflammatory analgesic aerosol stock solution of the present invention is as follows:
Further, the anti-inflammatory analgesic aerosol agent using the undiluted solution will be described in more detail with reference to Examples, but the present invention is not limited to such Examples.

[0032]

【Example】

Examples 1 to 5: BP having the formulation shown in Table 1
AA-containing anti-inflammatory analgesic aerosol stock solutions (Examples 1-5) were prepared. A stability test was conducted on the stock solution. That is, each stock solution was allowed to stand under the condition of 50 ° C., the quantitative change of the active ingredient: BPAA contained in the stock solution was measured after 1 month and 2 months, and the fluctuation of the pH value was observed. . In addition, as a comparative example, a stock solution (Comparative Examples A & B) having the formulation shown in Table 1 was prepared in the same manner, and the same stability test was performed. The results are shown together in Table 1.

[0033]

[Table 1]

As is clear from the results in the table, B of the present invention
It is found that the basic formulation of the aerosol stock solution containing PAA has no fluctuation in the content of the active ingredient and the pH, and is excellent in stability over time. For it,
In the formulation of the comparative example, BPAA contained in the undiluted solution
There was a problem in the stability because the content of s was changed with time and the pH was changed.

Examples 6 to 9: BPAA-containing aerosol stock solutions having the formulations shown in Table 2 (Examples 6 to 9)
Was prepared. The same stability test as in Example 1 was performed on the stock solution. That is, the quantitative change of the active ingredient: BPAA contained in each stock solution was measured after 1 month and 2 months under the condition of 50 ° C. and after 2 months under the condition of 40 ° C., and the pH thereof was also measured. The variation of the value was observed.
The results are also shown in Table 2.

[0036]

[Table 2]

As is clear from the results in the table, B of the present invention
It is found that the formulation of the undiluted aerosol solution containing PAA does not vary in the content of the active ingredient and the pH, and is excellent in stability over time.

Examples 10 to 14: BPAA-containing aerosol stock solutions having the formulations shown in Table 3 were prepared. Next, using this stock solution, a foamable aerosol anti-inflammatory analgesic was produced using LPG gas as a propellant.

[0039]

[Table 3]

Examples 15 to 18: BPAA-containing aerosol stock solutions having the formulation shown in Table 4 were prepared. Next, using this stock solution, a foamable aerosol anti-inflammatory analgesic was produced using LPG gas as a propellant.

[0041]

[Table 4]

Examples 21 to 25: BPAA aerosol stock solutions having the basic formulation shown in Table 5 were prepared. Next, a foamable aerosol agent was produced using this stock solution. The aerosol agent was subjected to a stability test, and the quantitative change of the active ingredient: BPAA contained in the stock solution, the change of pH value and the change of appearance were observed under various conditions. The results are also shown in Table 5.

[0043]

[Table 5]

As is clear from the results in the table, the foamable aerosol anti-inflammatory analgesic produced using the aerosol stock solution based on the basic formulation of the present invention containing BPAA has no fluctuation in the content of the active ingredient and the pH. It turns out that it is excellent in stability over time.

Examples 22 to 24: BPAA-containing aerosol stock solutions having the formulations shown in Table 6 were prepared. Then, using this stock solution, LPG gas as a propellant was filled at the compounding ratio shown in the table to produce a foaming aerosol agent. With respect to the aerosol agent, generation of foam (foaming property) and disappearance of foam (antifoaming property) were observed. In addition, the formulation of Comparative Example E was also examined. The results are shown in Table 6.

[0046]

[Table 6]

As is clear from the results in the table, it is clear that the aerosol anti-inflammatory analgesic produced using the undiluted aerosol solution of the present invention exhibits good foaming and defoaming properties.

Examples 25 to 26: BPAA-containing aerosol stock solutions having the formulations shown in Table 7 were prepared. Then, a foaming aerosol was produced using this stock solution.
With respect to the aerosol agent, generation of foam (foaming property) and disappearance of foam (antifoaming property) were observed. The results are also shown in Table 7.

[0049]

[Table 7]

As is clear from the results shown in Table 7, it is clear that the foaming aerosol prepared by using the stock solution of the present invention has good foaming and defoaming properties.

[0051]

As described above, the anti-inflammatory analgesic aerosol stock solution containing 4-biphenylylacetic acid of the present invention has excellent stability of the active ingredient, and in particular, the foamable aerosol prepared by using the stock solution is sprayed. When it does, it becomes foamy and defoams itself without breaking, and the active ingredient can be easily and uniformly applied, and a refreshing feeling can be imparted by the heat of vaporization of the propellant. Further, since the aerosol preparation produced using the stock solution of the present invention is instantly sprayed in the form of foam, the active ingredient is completely applied to the affected area without scattering to the surroundings, so that the nasal mucosa should be stimulated. Without
It has the effect of not causing coughing.
Furthermore, when actually using the aerosol prepared by using the stock solution of the present invention, the main drug contained in the composition has excellent skin permeability, has a strong anti-inflammatory and analgesic effect, and has few side effects on the skin, and the conventional 4-biphenylyl compound. It has the same anti-inflammatory and analgesic effect as acetic acid ointment, arthralgia,
It is medically useful as a therapeutic agent for inflammatory diseases such as low back pain, sprains, bruises, muscle aches and tendonitis.

Claims (7)

[Claims] 1. At least the following formulation: 4-biphenylylacetic acid 1 to 5% by weight, base 0.3 to 10% by weight, lower alcohol 10 to 50% by weight, water 40 to 80% by weight, and its pH Is in the range of 6.5 to 8.0. 4-biphenylylacetic acid composition liquid. 2. The composition liquid according to claim 1, which has a pH in the range of 7.0 to 8.0. 3. The base is mono-, di- or tri-
The composition liquid according to claim 1, which is a (lower alkanol) amine. 4. The base is an organic base such as ethanolamine, diethanolamine, diisopropanolamine, triethanolamine, 2-amino-2- (hydroxymethyl) -propane-1,3-diol).
The composition liquid described. 5. The composition liquid according to claim 1, wherein the lower alcohol is methanol, ethanol, propanol or isopropanol. 6. At least the following formulation: 4-biphenylylacetic acid 2-3 wt%, organic base 0.5-7 wt%, lower alcohol 20-40 wt%, water 50-70 wt% The composition liquid according to claim 1, which has a pH in the range of 7.0 to 8.0. 7. An anti-inflammatory analgesic aerosol stock solution.
7. The composition liquid according to 6 above.