JPH0372433A - Foamy aerosol preparation - Google Patents

Abstract

PURPOSE:To provide a highly safe foamy aerosol preparation exhibiting an excellent drug activity, producing a fine foam when sprayed and not having any irritation against the mucous membrane of nose cavity by compounding an acidic non-steroid antiphlogistic analgesic compound as an active ingredient, an absorption accelerating agent, etc., and further a propellant. CONSTITUTION:0.2-5wt.% of an acidic non-steroid antiphlogistic analgesic compound such as ibuprofen, indomethacin or ketoprofen as an active ingredient, 1-20wt.% of an absorption-accelerating agent such as crotamiton or peppermint oil, 0.3-10wt.% of a surfactant such as polyoxyethylene (20) polyoxypropylene (8), 0.01-5wt.% of a pH-adjusting agent such as diisopropanolamine and 10-50.wt% of purified water are charged to a pressure container. The container is equipped with a valve, hermetically sealed and subsequently press-filled with 10-50wt.% of a propellant such as liquid petroleum gas to provide the objective foamy aerosol preparation. The preparation has the good percutaneous absorbability of the active ingredient, an excellent drug effect, no tackiness, a rapidly foam-breaking property and a good touch and useful in an orthopedic surgery region.

Description

DETAILED DESCRIPTION OF THE INVENTION (1) Industrial Field of Application The present invention relates to a foam aerosol preparation containing an acidic non-steroidal anti-inflammatory analgesic compound as an active ingredient. More specifically, the present invention relates to a foam aerosol preparation containing an acidic nonsteroidal anti-inflammatory analgesic compound as an active ingredient and useful as a therapeutic agent for orthopedic diseases such as muscle pain, lower back pain, and joint pain.

(2) Prior art Until now, the prior art of aerosol preparations containing acidic anti-inflammatory analgesic compounds as active ingredients is
Aerosol formulations containing indomethacin 3117 are known. This is a conventionally known aerosol formulation containing indomethacin. Also, JP-A-61-26
No. 6,428, the present inventors filed an application for an aerosol formulation containing a non-steroidal anti-inflammatory analgesic compound. This is a Tarafking type foam aerosol preparation, which is a completely different invention from the foam aerosol preparation of the present invention.

(3) Problems to be solved by the invention In general, acidic anti-inflammatory and analgesic compounds have strong anti-inflammatory effects and do not have serious side effects, so they are widely used in many formulations such as oral or external preparations in the orthopedic field. has been done.

However, when made into an aerosol formulation, acidic anti-inflammatory and analgesic compounds irritate the nasal mucosa, causing sneezing and
In severe cases, it could cause asthma, and there were problems with the formulation. Therefore, an object of the present invention is to produce an aerosol formulation containing an acidic anti-inflammatory analgesic compound that does not irritate the nasal mucosa.

(4) Means for solving the problem In view of the above situation, the present inventors conducted intensive research, and as a result, solved the above problem by blending an acidic anti-inflammatory analgesic compound into a foamy aerosol preparation. I found out that it can be done. That is, the present invention relates to an anti-inflammatory and analgesic foam aerosol preparation for external use, characterized in that a propellant is blended into a stock solution consisting of an acidic anti-inflammatory analgesic compound, a surfactant, an absorption enhancer, and purified water.

The present invention will be explained in more detail below.

Acidic anti-inflammatory analgesic compounds used in the present invention include, for example, ibuprofen, indomethacin, ketoprofen, flurbiprofen, naproxen, pranoprofen, sulprofen, felbinac, diclofenanoc, pirprofen, sulindac, miloprofen, tiaprofen, protidic acid, fenbufen. , loxoprofen, ketorolasoc, belumobrofen, nabumetone and its ester derivatives. These are blended in a range of 0.2 to 5% by weight, preferably 0.3 to 4% by weight, depending on the effective amount of each. In addition to these active ingredients, local irritants such as menthol, camphor, peppermint oil, nonylic acid vanillylamide, and cabsaicin can be added as adjuvants.

As absorption enhancers, crotamiton, benzyl alcohol, glycol salicylate, peppermint oil, carbon Dca-C
Alcohol esters of monocarboxylic acids of I8, such as diisopropyl adipate, diethyl sebacate, diisopropyl sebacate, isopropyl acetic acid, isopropyl palmitate, liquid higher alcohols such as oleyl alcohol, 2-octyldodecanol, 2-hexyl Examples include decanol. These absorption enhancers are blended in an amount of 1 to 20% by weight, preferably 2 to 10% by weight, singly or in combination of two or more. As the surfactant, both ionic and nonionic surfactants can be used, but nonionic surfactants are particularly preferred. Examples of these surfactants include sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester,
Polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycol fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether,
Examples include polyoxyethylene polyoxybrobylene alkyl ether, polyoxyethylene phenyl ether, and higher alcohol phosphate ester. These surfactants can be used singly or in combination of 0.3 to 10
% by weight, preferably 0.5-5% by weight, more preferably 1-4% by weight. In addition, an emulsification aid may be added for the purpose of assisting the emulsification of these surfactants. Examples of these emulsifying aids include cetanol, stearyl alcohol, cetostearyl alcohol,
Examples include cholesterol, higher alcohols such as behenyl alcohol, lecithin, and saponin. Examples of the pH adjuster include inorganic bases such as potassium hydroxide, sodium hydroxide, and aqueous ammonia, and organic bases such as diethanolamine, diisopropanolamine, triisopropanolamine, and triethanolamine.

These pH adjusters are 0.01 to 5% by weight, and the pH of the formulation is
is blended in an amount of 4 to 9, preferably 5 to 8. In addition, a preservative may be added if necessary.

As the preservative, a suitable amount of commonly used preservatives such as parabens such as methylparaben, ethylparaben and propylparaben, and phenols such as isopropylmethylphenol and thymol are blended.

In addition, other additives include powders such as talc, silicone powder, and nylon powder, and moisturizers such as propylene glycol, 1°3-butylene glycol, and 3-methyl-1,3-butanediol to improve the feeling of use. agent,
Also, ethanol, isopropanol, etc. can be blended. Propellants include liquefied natural gas, n-pentane, isopentane, Freon 11, Freon 12, and Freon 14.
2b1 Freon 123, Freon 134a, Freon 124,
Propellants commonly used in aerosol preparations, such as fluorocarbon gases such as Freon 132b and Freon 133a, dimethyl ether, and carbon dioxide gas, are used. The amount of these propellants is in the range of 10 to 50% by weight and the pressure of the formulation is 1 to 8 kg.
/cd.

Next, a method for producing the foamy aerosol formulation of the present invention will be described.

To produce the aerosol formulation of the present invention, first, an absorption enhancer is added to the active ingredient, dissolved or dispersed, a surfactant,
After adding the pH adjuster, purified water and other additives, the valve is sealed and the propellant is injected. The above manufacturing method is only one example, and it is possible to manufacture the device even if the order of the manufacturing steps is partially changed.

EXAMPLES The present invention will be explained in more detail with reference to Examples below.

Example 1 Add 2g of ketoprofen to 3g of Chronomoton and heat at 70°
It was heated to dissolve. To this, 1.3-butylene glycol 1g 1 cholesterol 1g 1 polyoxyethylene (2
0) Polyoxypropylene (8) Cetyl ether 2g1
0.1 g of diisopropanolamine and 60 g of water were added and emulsified. This was placed in a pressure-resistant container, a valve was attached and sealed, and 17.6 g of liquefied petroleum gas was pressurized to obtain an anti-inflammatory and analgesic foam aerosol preparation.

Example 2 1 g of ketoprofen was added to 5 g of diethyl sebacate and 0.5 g of hafka oil and dissolved by heating to 70°. To this were added 2 g of 1.3-butylene glycol, 1 g of cetostearyl alcohol, 1 g of polyoxyethylene (20), polyoxypropylene (8), cetyl ether, 0.1 g of triethanolane, and 60 g of water to emulsify. This was placed in a pressure-resistant container, a valve was attached and sealed, and 17.6 g of liquefied petroleum gas was pressurized to obtain an anti-inflammatory and analgesic foam aerosol preparation.

Example 3 Add 2 g of ketoprofen and 2 g of z-menthol to 5 g of diisopropyl adipate, 0.5 g of hafka oil, and heat at 70°
It was heated to dissolve. To this were added 2 g of 1.3-butylene glyco1, 1 g of cholesterol, 1 g of talc, 1 g of polyoxyethylene (20) polyoxypropylene (8) cetyl ether, 0.2 g of diisopropanol, and 60 g of purified water to emulsify. This was placed in a pressure-resistant container, a valve was attached and sealed, and 17.6 g of liquefied petroleum gas was pressurized to obtain an anti-inflammatory and analgesic foam aerosol preparation.

Example 4 2 g of felbinac and 2 g of l-menthol were added to 2 g of crotamiton and dissolved by heating to 70'.

Add to this 2g of propylene glycol and 1g of cholesterol.
1 talc 1g 1 ethanol 5g 1 polyoxyethylene (
20) Polyoxypropylene (8) cetyl ether 1g
1 Diisopropanol 1 F1. Og and purified water 60g
was added to emulsify. This was placed in a pressure-resistant container, a valve was attached and sealed, and 17.6 g of liquefied petroleum gas was pressurized to obtain an anti-inflammatory and analgesic foam aerosol preparation.

Example 5 Add 2 g of ketoprofen to 2 g of crotamiton and heat at 70°
It was heated to dissolve. Add to this 2g of propylene glycol
1 cholesterol 1g 1 squalane 2g, talc 1g 1
Polyoxyethylene (20) Polyoxypropylene (8
) 2 g of cetyl ether, 0.
2 g, 0.1 g of methylparaben, and 60 g of purified water were added to emulsify. After putting this in a pressure-resistant container and sealing it with a valve, liquefied petroleum gas/dimethyl ether (70/30
vt%) was injected under pressure to obtain an anti-inflammatory and analgesic foam aerosol preparation.

Example 6 1 g of ketoprofen was added to 2 g of oleyl alcohol and 5 g of diethyl sebacate, and the mixture was dissolved by heating at 70°. Add this to 2g of propylene glycol and 11g of cholesterol.
g1 carboxyvinyl polymer 0.1%, talc 1g1
5 g of polyoxyethylene (20) polyoxypropylene (8) cetyl ether, 1 g of polyoxyethylene (23) cetyl ether, 0.2 g of diisopropanolamine, and 60 g of purified water were added and emulsified.

This was placed in a pressure-resistant container, a valve was attached and sealed, and 17.6 g of liquefied petroleum gas was pressurized to obtain an anti-inflammatory and analgesic foam aerosol preparation.

Example 7 Add 2g of ketoprofen to 2g of crotamiton and add 70”
It was heated to dissolve. Add to this 2g of propylene glycol
1 cholesterol 1g 1 carboxyvinyl polymer 0.
1% talc, 1 g of ethanol, 1 g of polyoxyethylene (20) polyoxypropylene (8) cetyl ether, 1 g of monododecyl phosphate, 1.2 g of diisopropanolamine and 60 g of purified water were added and emulsified. This was placed in a pressure-resistant container, a valve was attached and sealed, and 17.6 g of liquefied petroleum gas was pressurized to obtain an anti-inflammatory and analgesic foam aerosol preparation.

Example 8 1 g of indomethacin was added to 3 g of crotamiton and 70"
It was heated to dissolve. Add to this 2 g of 1,3-butylene glycol, 1 g of cholesterol, 1 g of polyoxyethylene (2
0) Polyoxypropylene (8) Cetyl ether 1g1
and triethanolamine 0.08 g and purified water 60
g was added to emulsify. This was placed in a pressure-resistant container, a valve was attached and sealed, and 17.6 g of liquefied petroleum gas was pressurized to obtain an anti-inflammatory and analgesic foam aerosol preparation.

Example 9 Add 1 g of 0 xobrofone to 3 g of crotamiton and add 70
' to dissolve it. Add to this 1.3=butylene glycol 2g1 cholesterol Ig, polyoxyethylene (
20) Polyoxypropylene (8) cetyl ether 1g
, and triethanolamine 0.08 g and purified water 6
0g was added and emulsified.

This was placed in a pressure-resistant container, a valve was attached and sealed, and 17.6 g of liquefied petroleum gas was pressurized to obtain an anti-inflammatory and analgesic foam aerosol preparation.

Example 10 Add 2 g of ketoprofen to 1 g of crotamiton and heat at 70°
It was heated to dissolve. Add to this 1.3-butylene gelicol 2g 1 oleyl alcohol 2g 1 cholesterol 0.
1 g of polyoxyethylene (1o) octylphenyl ether and 49.9 g of purified water were added to emulsify. After putting this into a pressure-resistant container and sealing it with a valve, 23.2 g of liquefied natural gas was injected under pressure to obtain an anti-inflammatory and analgesic foam aerosol preparation.

Reference Example 1 0.75 g of indomethacin is dissolved in a mixture of 3 g of diisopropyl adipate, 5 g of polyethylene glycol monolaurate, 10 g of ethanol, 10 g of isoprobanol, and 5 g of macrogol 400, and then 0.1 g of dibutylhydroxytoluene is added and dissolved. Next, 23 g of purified water in which 0.2 g of diisopropanolamine was dissolved
was added and mixed. Next, this was placed in a pressure-resistant container, and after a valve was attached and sealed, 10 g of liquefied petroleum gas and 15 g of dimethyl ether were pressurized into the container to obtain an anti-inflammatory and analgesic foam aerosol preparation.

Test Example 1 The aerosol formulations of Example 1 and Reference Example 1 were examined for irritation to the nasal mucosa.

The aerosol formulations of Example 1 and Reference Example 1 were sprayed onto the upper arms of 20 healthy male adults, and the irritation to the nasal mucosa was examined. The results are shown in Table 1.

As can be seen from the results in Table 1, compared to the aerosol formulation of the reference example, the aerosol formulation of the present invention did not cause any irritation to the nasal mucosa since the contents did not scatter.

(5) Effects of the Invention The foam aerosol preparation containing the acidic anti-inflammatory analgesic compound obtained by the present invention as an active ingredient forms fine bubbles when sprayed and does not pop, so the active ingredient does not irritate the nasal mucosa and is safe. It is excellent because of its high quality. In addition, since it contains an absorption enhancer, the drug has good transdermal absorption and excellent medicinal efficacy. Furthermore, since it is non-sticky and has continuous foam, it feels good on use and is suitable as a formulation for orthopedic surgery.

Claims (1)

[Scope of Claims] 1) A foam aerosol preparation containing an acidic non-steroidal anti-inflammatory analgesic compound as an active ingredient. 2) 0.2 to 5% by weight of acidic non-steroidal anti-inflammatory analgesic compound, 1 to 20% by weight of absorption enhancer, and 0.3 to 0.3% by weight of surfactant.
10% by weight, pH adjuster 0.01-5% by weight, purified water 1
A foam aerosol formulation consisting of 0 to 50% by weight and 10 to 50% by weight of propellant. 3) Acidic nonsteroidal anti-inflammatory analgesic compounds include ibuprofen, indomethacin, ketoprofen, flurbiprofen, naproxen, pranoprofen, sulprofen, felbinac, diclofenac, pirprofen, sulindac, miloprofen, tiaprofen,
The foam aerosol preparation according to claim 1 or 2, which is protidic acid, fenbufen, loxoprofen, ketorolac, belmoprofen, napmetone, and derivatives thereof. 4) Absorption enhancer is crotamiton, benzyl alcohol,
Glycol salicylate, peppermint oil, carbon number C_4 to C_
3. The foamy aerosol preparation according to claim 2, which is an alcohol ester of monocarboxylic acid 1_8 and a liquid higher alcohol.