JP3302995B2 - Aerosol composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a non-aqueous external aerosol composition containing a non -steroidal anti-inflammatory external preparation as an active ingredient. More specifically, the present invention relates to a non -aqueous external aerosol composition containing a non-steroidal anti-inflammatory external preparation as an active ingredient and discharged in the form of foam or gel.

[0002]

2. Description of the Related Art Non-steroidal anti-inflammatory agents such as indomethacin have been widely used.

When a nonsteroidal anti-inflammatory drug is administered,
Oral administration and suppository administration, which are conventional administration methods, have no problem in short-term administration, but long-term administration causes side effects such as gastrointestinal disorders, renal and hepatic disorders. Therefore, external preparations and the like are commercially available for the purpose of penetrating a drug into an affected part by a route different from oral administration or the like.

[0004] However, applying an external preparation to the skin surface is quite painful for the patient when the affected area is severely painful. JP-A-61-83117 proposes an aerosol that can alleviate such pain.

[0005]

However, the aerosols are usually sprayed in the form of a mist, which often irritates the nasal mucosa and causes coughing. Therefore, the same side effects as when taken orally are a problem. It is becoming.

JP-A-3-72432 proposes a foamy aerosol formulation that does not irritate the nasal mucosa, but is often used when the content of purified water is high and the stability of the active ingredient over time is problematic. Or for nasal mucosal irritation.

[0007]

Means for Solving the Problems The present inventor has conducted intensive studies in order to solve such a problem. As a result, the present invention contains a polyhydric alcohol as a stock solution in an amount of 70% (% by weight, hereinafter the same) or more, and is used for non-steroidal anti-inflammatory use. The present inventors have found that an aerosol composition containing an agent, for example, which can be discharged in the form of a foam or a gel, can solve the above problems, and have reached the present invention.

[0008]

That is, the present invention provides a non-aqueous non-aqueous solution characterized in that the stock solution contains at least 70% by weight of a polyhydric alcohol and a non-steroidal anti-inflammatory external preparation.
An aerosol composition for use .

[0009]

EXAMPLES As described above, the stock solution of the aerosol composition of the present invention contains at least 70% of a polyhydric alcohol.

Examples of the polyhydric alcohol include glycerin, propylene glycol, 1,4-butylene glycol, 1,3-butylene glycol, diethylene glycol, triethylene glycol, dipropylene glycol, hexylene glycol, polyethylene glycol and the like. One or two or more are used.
Among these polyhydric alcohols, glycerin, propylene glycol, 1,3-butylene glycol, and polyethylene glycol are good humectants because they have high safety to the human body and are commonly used as moisturizing ingredients. Particularly preferred.

The aerosol composition of the present invention is preferably made non-aqueous in view of the stability over time of the non-steroidal anti-inflammatory external preparation. Therefore, it is preferable that the polyhydric alcohol be contained in an anhydrous state or a state close thereto. As a result, when the aerosol composition of the present invention is applied to the skin, a mild exothermic reaction takes place by absorbing the water in the upper layer of the skin, and the exotherm brings a feeling of warmth and at the same time expands the capillaries of the skin, Immediate penetration of the active ingredient into the skin.
Furthermore, the fever exhibits an action of promoting blood circulation in the affected area, and accordingly, the time required for the active ingredient to reach the local area is reduced.

The amount of the polyhydric alcohol used is 70% or more;
Preferably it is at least 75%. When the amount used is less than 70%, there is a problem in the temporal stability of the non-steroidal anti-inflammatory anti-inflammatory agent, and the dispersibility becomes poor. On the other hand, the effect of promoting blood circulation due to warmth tends not to be expected. . There is no upper limit, but it may be up to about 96% in consideration of the amount of the active ingredient.

The amount of the polyhydric alcohol used is appropriately set within the above range depending on the form of the obtained aerosol composition. The form of the aerosol composition is determined by the state of the aerosol composition discharged from the aerosol container,
It is most preferable to discharge in the form of foam or gel due to the problem of inhalation toxicity.

[0014] Examples of the nonsteroidal anti-inflammatory external preparation contained in the stock solution include indomethacin, bufexamac, ibuprofen, suprofen, flurbiprofen, ketoprofen, piroxicam, felbinac and derivatives thereof. It is not limited.

[0015] Two or more nonsteroidal anti-inflammatory external preparations may be used in combination.

The non-steroidal anti-inflammatory external preparation is dissolved or dispersed in a stock solution for aerosol composition. When it is dispersed, it is usually blended with the stock solution as a finely pulverized product. The particle size of the finely pulverized product is preferably 1 to 100 μm, more preferably about 2 to 50 μm. If the particle size is less than 1 μm, the particles tend to aggregate in the aerosol composition. If the particle size is more than 100 μm, valves and the like may be clogged.

The amount of the non-steroidal anti-inflammatory agent for external use is preferably 0.1 to 5%, more preferably 0.2 to 4%, in the stock solution. When the amount is less than 0.1%, the effect of the non-steroidal anti-inflammatory external preparation is not sufficiently exhibited, and when it exceeds 5%, there is a possibility that problems such as side effects may occur.

The stock solution used in the aerosol composition of the present invention may further contain a foam stabilizer and / or a gelling agent or an auxiliary agent as appropriate.

Examples of the foam stabilizer and / or gelling agent include alkyl sulfates, polyoxyethylene alkyl ether sulfates, and N-acylamino acids when the aerosol composition of the present invention is discharged in the form of foam. And salts thereof, N-acylmethyl taurine salt, polyoxyethylene alkyl ether acetate, α-olefin sulfonate, alkyl sulfocarboxylate, alkyl phosphate,
Anionic surfactants such as polyoxyethylene alkyl ether phosphate; sorbitan fatty acid ester, glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbite fatty acid ester, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil Nonionic surfactants such as polyoxyethylene alkylamine, polyoxyethylene fatty acid amide ester, polyoxyethylene glycerin fatty acid ester, and polyoxyethylene alkyl ether;
Cationic surfactants such as alkylammonium alkylbenzylammonium salts, diethylaminoethylamide stearate, and lanolin-derived quaternary ammonium salts; gelatin, methylcellulose, ethylcellulose;
Thickeners such as hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose, xanthan gum and carboxyvinyl polymer; higher alcohols having 10 to 18 carbon atoms such as caprylic alcohol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol; ethanol, isopropyl alcohol One or two or more kinds of lower alcohols having 2 to 4 carbon atoms such as normanpropyl alcohol are used. When a higher alcohol is blended, a lower alcohol is preferably used in combination. Among the lower alcohols, ethanol and isopropyl alcohol are particularly preferred because they help solubilize the higher alcohol, enable the incorporation of various active ingredients, and facilitate obtaining a uniform stock solution.

The amount of the foam stabilizer and / or gelling agent is preferably 0.1 to 20% in the stock solution.

Examples of the auxiliary agent include methyl salicylate, glycol salicylate, l-menthol, dl
-Anti-inflammatory agents such as camphor and peppermint oil, fragrances, silicone oils, esters such as isopropyl myristate, isopropyl palmitate, diethyl sebacate, diisopropyl adipate, various ketones, pH adjusters, solvents, preservatives, antioxidants Agents and the like.

In order to improve the feeling of use, talc,
Powders such as nylon powder and zinc oxide can also be blended.

The amount of the auxiliary agent used is usually 10% or less in the stock solution.

The aerosol composition of the present invention uses a stock solution as described above, and is prepared by blending the stock solution and a propellant.

As the propellant, liquefied petroleum gas (mixture of propane, i-butane, n-butane, etc .;
Abbreviated), dimethyl ether, fluorocarbon (F)
22, fluorocarbon 142b, fluorocarbon 1
A liquefied gas such as 34a, fluorocarbon 123 or the like, or a compressed gas such as CO ₂ , N ₂ O, N ₂ or compressed air is preferable. When a liquefied gas such as LPG is used, the gas is discharged in a highly foamed foam, and when a compressed gas such as CO ₂ is used, the gas is discharged in a low foamed foam.

Among the aerosol compositions of the present invention, the aerosol composition discharged in the form of highly foamed foam includes a stock solution 80
-98%, further 85-97% and propellant 20-2%, furthermore 15-3%.
If the stock solution is less than 80 %, sufficient shaking tends to be required before use, and if it exceeds 98%, the desired highly foamed foam tends not to be formed.

As the stock solution for high foaming, polyhydric alcohol is 70% or more, preferably 96% or less, more preferably 75 to 95%, and a foam stabilizer and / or a gelling agent 0.1
-20%, more preferably 0.5-15%, a nonsteroidal anti-inflammatory external preparation 0.1-5% and an adjuvant 10% or less are preferred. If the amount of the foam stabilizer is less than 0.1%, it is difficult to obtain good foam, and if it exceeds 20%, the surfactant may cause skin irritation, separation of higher alcohol, solidification of the stock solution, and increase in foam hardness. Tends to occur. When the proportion of the polyhydric alcohol exceeds 96%, the content of other components inevitably decreases.

Typical examples of the low-foaming foam-dispersed eyazole composition are those comprising a stock solution of 95 to 99.9%, more preferably 97 to 99.5%, and a propellant of 0.1 to 5%, further preferably 0.5 to 3%. As If the stock solution is less than 95%,
High aerosol product pressure is dangerous. If it exceeds 99.9%, the product pressure will be low and it will not be possible to use it to the end. The discharged low foaming foam is a foam that is easily broken.

Examples of the undiluted solution for low foaming are the same as the undiluted solution used for the aerosol composition discharged in the form of highly foamed foam.

When the aerosol composition of the present invention is discharged in the form of a gel, the interior of the aerosol container is divided into a first room and a second room, and the first room is filled with a stock solution for aerosol. In addition, it is preferable to use a container filled with a propellant in the second chamber. The stock solution in the case of a gel, the same thing is illustrated with stock to be used in the aerosol composition discharged into the foam, in particular the addition of such thickening agents, 50Cp～100,000cp a stock solution viscosity It is preferred that

Next, the aerosol composition of the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Examples 1 to 7, Comparative Example 1 The components shown in Tables 1 and 2 were mixed and dissolved (partially dispersed) to prepare a stock solution, and the obtained stock solution was mixed with the propellants shown in Tables 1 and 2. Pressure container for aerosol so that it becomes 100 g (full quantity: 20
0 ml), sealed, and fitted with a spray device to produce an aerosol product.

However, in Example 7, the inside of the pressure container for aerosol was divided into a first room and a second room, and the first room was filled with the stock solution and the second room was filled with the propellant. Aerosol products were manufactured.

With respect to the obtained aerosol product, the discharge state, irritation to the nasal mucosa, and warmth were examined according to the following methods.

(A) Discharge Condition The aerosol container was well dropped at 25 ° C. and discharged, and the condition was visually observed.

(B) Irritation to the nasal mucosa The contents of a nasal mucosa were evaluated by discharging the contents from an aerosol product to the upper arm of 10 male and 10 female panelists in their 30s. The evaluation was made according to criteria.

A: More than 18 people are not irritating. B: 13-17 people are not irritating. C: 8 to 12 people are not irritating. D: 3-7 people are not irritating. E: Less than 2 people have no irritation.

(C) Warmth The contents discharged from the aerosol product were applied to the back of the hands of the above panelists and evaluated according to the following evaluation criteria.

A: More than 18 people felt warmth. B: 13 to 17 people felt warmth. C: 8 to 12 people felt warmth. D: 3 to 7 people felt warmth. E: Three or less felt warmth.

[0040]

[Table 1]

[0041]

[Table 2]

As is evident from the results shown in Tables 1 and 2, the aerosol composition of the present invention becomes foamy or gel-like when discharged, has little scattering, and has little irritation to the nasal mucosa. It can be seen that there is a feeling of warmth and blood circulation also has a promoting effect.

[0043]

The aerosol composition of the present invention becomes foamy or gel-like when discharged, so that it does not irritate the nasal mucosa, or contains a polyhydric alcohol, so that the feeling of warmth promotes blood circulation. It shows.

Continuation of the front page (51) Int.Cl. ⁷ identification code FI A61K 45/00 A61K 45/00 47/10 47/10 A61P 29/00 A61P 29/00 (58) Fields investigated (Int. Cl. ⁷ , (DB name) A61K 9/12 A61K 31/165 A61K 31/19 A61K 31/405 A61K 31/54 A61K 45/00 A61K 47/10 A61P 29/00

Claims (7)

(57) [Claims] 1. A non-aqueous external aerosol composition comprising a stock solution containing at least 70% by weight of a polyhydric alcohol and a non-steroidal anti-inflammatory external preparation. 2. The composition according to claim 1, wherein said stock solution comprises at least 70% by weight of a polyhydric alcohol, 0.1 to 20% by weight of a foam stabilizer and / or a gelling agent,
Non-steroidal anti-inflammatory external preparation 0.1-5% by weight and auxiliary
The aerosol composition according to claim 1, comprising 10% by weight or less. 3. The non-steroidal anti-inflammatory external preparation is at least one selected from bufexamac, ibuprofen, indomethacin, ketoprofen, flurbiprofen, felbinac, suprofen, piroxicam and derivatives thereof. Aerosol composition. 4. An aerosol composition comprising 80 to 98% by weight of the stock solution according to claim 1 and 2 to 20% by weight of a liquefied gas as a propellant. 5. An aerosol composition comprising 95 to 99.9% by weight of the stock solution according to claim 1 and 0.1 to 5% by weight of a compressed gas as a propellant. 6. The aerosol composition according to claim 1, wherein the composition is discharged in the form of a foam or a gel. 7. The method according to claim 7, wherein the polyhydric alcohol is glycerin,
1 of lene glycol and 1,3-butylene glycol
The method according to claim 1, 2, 3, 4, 5, or 6, which is at least one species.
Aerosol composition.