JPH11209267A - Aerosol composition for antiinflammatory gel - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an aerosol composition for antiinflammatory gels, capable of being adhered in a gel-like state without scattering a raw liquid and dripping the raw liquid after adhered, even when used in the form of an antiinflammatory agent containing indomethacin. SOLUTION: This aersol composition for antiinflammatory gels comprises 100 pts.wt. of a raw liquid comprising 0.75-1.0 wt.% of indomethacin, 0.01-2.0 wt.% of a carboxyvinyl polymer, 10-60 wt.% of an alcohol and/or a glycol, and the remainder of water, and 40-100 pts.wt. of a propellant comprising dimethyl ether. Thereby, the scattering of the indomethacin on spraying can be inhibited, and the adhesion rate of the raw liquid to a target site in a gel-like state while preventing the dripping of the raw liquid, is improved.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an aerosol composition for an anti-inflammatory gel, which is capable of spraying an anti-inflammatory agent for human body containing indomethacin in a gel form.

[0002]

2. Description of the Related Art At present, as an anti-inflammatory agent containing indomethacin, which is a non-steroidal anti-inflammatory analgesic, a cream-type one put in a tube and a liquid-type one put in an application container are used. It has been considered that a stock solution containing indomethacin and a propellant are filled in an aerosol container and sprayed for use to facilitate use.

On the other hand, an aerosol composition of an anti-inflammatory agent for the human body (other than indomethacin) which has been conventionally used is composed of a stock solution containing an anti-inflammatory component such as methyl salicylate, and a propellant, and comprises a foam or mist. And the like.

[0004]

However, in the case of an aerosol composition in the form of a foam or a mist, the sprayed particles have a small particle diameter and are easily scattered around, and a high proportion of the anti-inflammatory component adheres to the target site. There is a problem that it can not be done.

[0005] Another problem is that the viscosity of the anti-inflammatory component attached to the application site is low, so that the so-called dripping easily flows down from the application site.

Accordingly, it has been proposed to increase the viscosity by adding a thickener and alcohols to the stock solution to form a gel (Japanese Patent Application Laid-Open No. 7-101851). When applied to an aerosol composition comprising a stock solution as a component and a propellant, there is a problem that a thickener is deposited when dimethyl ether is filled as a propellant due to the presence of a large amount of alcohols. .

SUMMARY OF THE INVENTION The present invention has been made to solve the problems of the prior art. Even if an anti-inflammatory agent containing indomethacin is used, there is no spattering of the stock solution or dripping after adhering, and the inflammation agent is applied in a gel form. It is an object of the present invention to provide an aerosol composition for an anti-inflammatory gel which can be used.

[0008]

In order to solve the problems of the prior art, the aerosol composition for anti-inflammatory gel according to claim 1 of the present invention comprises (A) indomethacin 0.7
5 to 1.0% by weight, (B) 0.01 to 2.0% by weight of carboxyvinyl polymer, (C) 10 to 60% by weight of alcohol and / or glycol, (D) 35 to 8 of water
It is characterized by comprising 100 parts by weight of a stock solution containing 9.24% by weight, and 40 to 100 parts by weight of a propellant having dimethyl ether.

Here, indomethacin is a chemical name: 1
-(P-chlorobendyl) -5-methoxy-2-methylindole-3-acetyl acid, molecular formula: C
A non-steroidal anti-inflammatory analgesic that is ₁₉ H ₁₆ ClNO ₄ .

[0010] Carboxybinl polymer is a water-soluble polymer of a cross-linked acrylic acid polymer, which acts as a thickening agent that thickens and gels the stock solution by containing it in the stock solution. It is.

The alcohol and / or glycol are alcohol alone, glycol only, or a mixture of alcohol and glycol, and act as a solubilizing agent for dissolving the inflammation component indomethacin in a stock solution. Dimethyl ether (DME), which is a propellant to be dissolved, also functions as a dissolution aid for dissolving in a stock solution.

As the water, purified water (ion-exchanged water) is usually used and constitutes a stock solution. According to such an anti-inflammatory gel aerosol composition, scattering of indomethacin, which is an active ingredient at the time of injection, is suppressed, and is attached to a target site in a gel form, preventing dripping and improving the adhesion rate. become.

Further, the aerosol composition for an anti-inflammatory gel according to the second aspect of the present invention has the following features.
The undiluted solution contains (E) 0.01 to 2.0% by weight of amines and / or bases.

Here, the amines and / or bases act as a neutralizing agent for the carboxyvinyl polymer as a thickening agent.
Alternatively, a mixture of amines and bases is used.

[0015] Such an anti-inflammatory gel aerosol composition also neutralizes the carboxyvinyl polymer, suppresses the scattering of indomethacin, which is the active ingredient at the time of injection, adheres to the target site in a gel form, and causes dripping. This can be prevented and the adhesion rate can be improved.

Furthermore, the aerosol composition for anti-inflammatory gel according to claim 3 of the present invention, in addition to the constitution according to claim 1 or 2, further comprises (F) a primary particle diameter of 0.1 to 50 microns in the stock solution. And 0.1 to 10% by weight of an inorganic powder and / or an organic powder having

Here, the inorganic powder and / or the organic powder impart moderate lubricity and spreadability to indomethacin, which is a gel-like active ingredient adhered to an application site by being contained in a stock solution, It is intended to improve the usability.

According to such an aerosol composition for anti-inflammatory gel, the aerosol composition for anti-inflammatory gel according to claim 1 or 2 is further imparted with a suitable sliding property and spreadability, thereby improving a feeling of use. become able to.

[0019]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the aerosol composition for anti-inflammatory gel of the present invention will be described in detail.

The aerosol composition for an anti-inflammatory gel according to the present invention comprises a stock solution containing an active ingredient and a propellant for spraying the same. The stock solution (1) comprises (A) indomethacin and (B) ) A carboxyvinyl polymer;
(C) alcohol and / or glycol, and (D)
Contains water as an essential component and (E) as an optional component
Some of them contain amines and / or bases and (F) inorganic powder and / or organic powder, and the propellant (2) contains dimethyl ether.
Hereinafter, each component of the aerosol composition for anti-inflammatory gel will be described.

(1) Stock solution (A) Indomethacin This indomethacin is an anti-inflammatory component which is an active ingredient, and is contained in the stock solution in the range of 0.75 to 1.0% by weight.

(B) Carboxyvinyl polymer The carboxyvinyl polymer increases the viscosity of the stock solution,
It acts as a thickener that suppresses splashing and dripping of the liquid at the time of injection, and the compounding amount is in the range of 0.01 to 2.0% by weight, preferably 0.1 to 1.0% by weight. Range.

When the compounding amount of the carboxyvinle polymer is 0.
When the amount is less than 01% by weight, the obtained stock solution cannot be sufficiently thickened and gelled, and the effect of preventing scattering and dripping cannot be sufficiently exhibited. On the other hand, when the compounding amount of the carboxyvinyl polymer exceeds 2.0% by weight, the viscosity of the obtained stock solution becomes too high, so that a good jet state cannot be achieved. The viscosity of the stock solution adjusted by this carboxyvinyl polymer is 500
~ 100,00 cp (20 ° C), more preferably 2,000-60,000 cp.
(20 ° C.).

As the carboxyvinyl polymer,
Carbopol manufactured by BF Goodrich Chemical Co., Ltd. and Hibiswako manufactured by Wako Pure Chemical Industries, Ltd. can be used.
Specifically, Carbopol 934, Carbopol 940, Carbopol 941, and Hibiswako 103, Hibiswako 104, and Hibiswako 10 manufactured by the former company
Commercially available products such as No. 5 can be suitably used.

(C) Alcohol and / or Glycol This alcohol and / or glycol is contained in the stock solution and acts as a solubilizer for indomethacin as an active ingredient, and also as a solubilizer for dimethyl ether (DME) as a propellant. It also acts as an agent and is contained as alcohol alone, glycol alone, or a mixture of alcohol and glycol.

Here, glycol is an aliphatic in which two hydroxyl groups are bonded to two different carbon atoms, and the general formula is represented by R (OH) ₂ .

Examples of the alcohol include ethyl alcohol and isopropyl alcohol, and examples of the glycol include 1,3 butylene glycol and propylene glycol. In particular, 1,3 butylene glycol and propylene glycol are indomethacin. In addition to acting as a solvent, it also acts as a stabilizer that suppresses hydrolysis of indomethacin.

As a mixture of alcohol and glycol, the mixing ratio is alcohol / glycol = 10 /
Those having a range of 90 to 90/10% by weight are used.

The blending amount of the alcohol and / or glycol in the stock solution (in the case of a mixture, the sum of both) is 1
The range is from 0 to 60% by weight, preferably from 25 to 35% by weight, and dimethyl ether (D
ME) to increase the solubility in water (about 35% by weight) and maintain a good spray state until the end of the product. 10% by weight of the alcohol and / or glycol
If it is less than 3, the solubility of indomethacin as an active ingredient and the solubility of dimethyl ether (DME) as a propellant cannot be sufficiently imparted to the obtained stock solution. On the other hand, if the amount of the alcohol and / or glycol exceeds 60% by weight, carboxyvinyl polymer is precipitated when dimethyl ether (DME) as a propellant is charged.

(D) Water As the water contained in the stock solution, purified water (ion-exchanged water) is usually used, and its blending amount is usually 35 to 89.2.
It is in the range of 4% by weight, preferably in the range of 50-70% by weight.

(E) Amines and / or bases The amines and / or bases act as a neutralizing agent for the carboxyvinyl polymer, but the carboxyvinyl polymer is not necessarily used after being neutralized. Since it may be used, it is used as an optional component, and is used as only amines, only bases, or a mixture of amines and bases.

When the carboxyvinyl polymer is not used after being neutralized, another thickener can be used instead of the carboxyvinyl polymer as the thickener. For example, xanthan gum, hydroxymethyl cellulose, or the like can be used. The same effect can be obtained as the aerosol composition for anti-inflammatory gel of the present invention (see Reference Examples 1 to 3 in Table 1 described later).

Examples of the amines and / or bases used as the neutralizing agent for the carboxyvinyl polymer include, for example, triethylamine and triethanolamine as the amines. Sodium and the like can be mentioned.

The amount of the amines and / or bases to be added to the stock solution (in the case of a mixture, the sum of the two) is
The content is in the range of 0.01 to 2.0% by weight, preferably 0.1 to 2.0% by weight.
1 to 1.0% by weight, and within this range,
The same weight as the carboxyvinyl polymer is blended.

(F) Inorganic powder and / or organic powder This inorganic powder and / or organic powder imparts appropriate slipperiness and spreadability to a gel-like stock solution sprayed on a site to be applied to a human body. To give a good feeling of use,
Since it is not always necessary, it is contained as an optional component, and is contained only as an inorganic powder, only an organic powder, or as a mixture of an inorganic powder and an organic powder.

As the inorganic powder and / or organic powder, for example, silica powder, talc powder,
Mica powder, silicic acid powder, catalin powder, calamine powder, zinc oxide powder and the like can be mentioned. For example, as organic powder, nylon 6 powder, nylon 12 powder, polyethylene powder, polypropylene powder, polystyrene powder, polymethyl methacrylate powder, PET powder and the like can be mentioned.

This inorganic powder and / or organic powder is
The primary particle size is usually in the range of 1 to 50 microns, preferably in the range of 2 to 20 microns.

If the primary particle size is less than 1 micron, secondary agglomeration tends to occur, while if the primary particle size exceeds 50 microns, clogging of the nozzle of the aerosol valve and the like tends to occur.

The mixing amount of the inorganic powder and / or the organic powder in the stock solution (the sum of the two in the case of a mixture) is usually
0.1 to 10% by weight, preferably 0.5 to
The range is 5% by weight, more preferably 1 to 3% by weight. If the blending amount of the inorganic powder and / or the organic powder in the stock solution is less than 0.1% by weight, the stock solution cannot be imparted with slipperiness and spreadability. Clogging is likely to occur.

(2) Propellant As the propellant constituting the aerosol composition for anti-inflammatory gel, a propellant having dimethyl ether (DME) as an essential component is used, and it is particularly preferable that the propellant is composed of only dimethyl ether.

The use of this dimethyl ether as a propellant has the effect of lowering the viscosity of the stock solution whose viscosity has been increased by the carboxyvinyl polymer. When the stock solution is filled in an aerosol container, the stock solution can be given fluidity. A good spray state can be maintained until all of the aerosol composition for anti-inflammatory gel, which is the content in the aerosol container, is jetted.

Further, dimethyl ether is vaporized after the spraying, and a high-viscosity gel-like stock solution remains at the application site to prevent dripping, and the dimethyl ether is vaporized even during the spraying. The material becomes a high-viscosity stock solution, and splashing of the liquid during spraying can be suppressed.

The mixing amount of the propellant having such dimethyl ether is usually from 40 to 100 parts by weight of the stock solution.
It is in the range of 100 parts by weight, preferably in the range of 50 to 85 parts by weight. If the compounding amount of the propellant having dimethyl ether is less than 40 parts by weight, it becomes impossible to spray all the contents in the aerosol container,
If it exceeds 100 parts by weight, it is difficult to suppress the pressure of the aerosol container.

Among such constituents, the stock solution contains (A) indomethacin, (B) a carboxyvinyl polymer, (C) an alcohol and / or glycol, and (D) water, and contains dimethyl ether as a propellant. The resulting anti-inflammatory gel aerosol composition is prepared and filled in an aerosol container.

When the aerosol composition for an anti-inflammatory gel, which is the content of the aerosol container, is sprayed toward the application site of the human body, dimethyl ether (DME), which is a propellant, is discharged while the content reaches the application site. The concentration of the stock solution is increased by vaporization, whereby the viscosity (cohesion) of the spray particles is improved, and the scattering of the contents to the surroundings is suppressed.

Further, a high-viscosity substance (gel) corresponding to the anti-inflammatory component in the stock solution adheres to the application site where the aerosol composition for anti-inflammatory gel is jetted, so that so-called dripping is prevented.

Further, since 1,3-butylene glycol and propylene glycol act as stabilizers for indomethacin, an anti-inflammatory component, the stability of the anti-inflammatory gel aerosol composition can be improved.

The aerosol composition for a flame-extinguishing gel obtained by blending (E) amines and / or bases with the above (A) to (D) as a stock solution among the constituent components is similarly prepared, and Is filled.

When the aerosol composition for an anti-inflammatory gel, which is the contents of the aerosol container, is sprayed toward the application site of the human body, the same effect as described above is exerted, and at the same time, a thickener is added with amines and / or bases. Certain carboxyvinyl polymers can be neutralized.

In addition, an aerosol composition for a flame-extinguishing gel obtained by blending (F) an inorganic powder and / or an organic powder with (A) to (D) or (A) to (E) as a stock solution among the constituent components. Is similarly adjusted and filled into an aerosol container.

When the aerosol composition for an anti-inflammatory gel, which is the contents of the aerosol container, is sprayed toward the application site of the human body, the same effects as in the above two cases can be obtained, and the inorganic powder and / or the organic powder can be used. By the compounding, the gel adhered to the application site can be given an appropriate sliding property and spreadability, and the feeling of use at the time of application can be improved.

[0052]

EXAMPLES Examples of the aerosol composition for a flame-extinguishing gel of the present invention will be described below with reference examples and comparative examples. In the following examples, the following three kinds of carboxyvinyl polymers were used.

(B) Carboxyvinyl polymer Carbopol 940 BF Hibiswako 104 manufactured by Goodrich Chemical Co., Ltd. Hibiswako 105 manufactured by Wako Pure Chemical Industries, Ltd. manufactured by Wako Pure Chemical Industries, Ltd. Xanthan gum and hydroxymethyl cellulose were used as thickeners when no agent was used.

(C) As the alcohol and / or glycol, 1,3 butylene glycol, propylene glycol, ethyl alcohol, and isopropyl alcohol were used alone or in combination of two or three.

(D) Purified water was used as water.

(E) Triethanolamine was used as amines and / or bases.

(F) As the inorganic powder and / or the organic powder, silica powder, nylon powder and talc powder were used alone or as a mixture.

Then, in accordance with the formulation shown in Table 1, 12 of Examples 1 to 6, Reference Examples 1 to 3, and Comparative Examples 1 to 3
An aerosol container was filled with the stock solution component and the propellant described above for each type to prepare an aerosol product containing the aerosol composition for anti-inflammatory gel.

In each of the examples, reference examples and comparative examples, an aerosol container made of aluminum was used, and the stem hole diameter of the aerosol valve was 0.45 mm and the hole diameter of the housing was 1.00 mm.

Examples 1 to 3 In Examples 1 to 3, carboxyvinyl polymers were neutralized using triethanolamine as a neutralizing agent.

Examples 4 to 6 In Examples 4 to 6, carboxyvinyl polymer was used without neutralizing triethanolamine as a neutralizing agent.

Reference Examples 1 to 3 In Reference Examples 1 to 3, xanthan gum and hydroxymethyl cellulose were used as thickeners.

Comparative Examples 1 to 3 In Comparative Examples 1 to 3, carboxyvinyl polymer as a thickener, triethanolamine as a neutralizing agent, inorganic powder such as silica powder and organic powder such as nylon powder were used. It does not include.

In Examples 1 to 6 and Reference Examples and Comparative Examples each containing the aerosol composition for anti-inflammatory gel prepared as described above as a content, the scattering state of the liquid, the slipperiness of the attached matter, and the content The stability and the particle size of the deposit were evaluated. Each evaluation method is as follows. The splattering state of the liquid was evaluated using the attached amount and the attached rate.

Each aerosol product was placed in a thermostat at 25 ° C. for 30 minutes.
After immersion for more than a minute, each aerosol product is sprayed onto the metal plate for 3 seconds from a position 10 cm away from the vertical surface of the 20 × 20 cm metal plate.

Then, the weight (g) of the content sprayed in 3 seconds and the weight (g) of the content adhering to the metal plate were determined.
From the ratio (wt%) of the undiluted solution in the contents, the adhesion amount (%) and the adhesion ratio (%) were determined based on the following formula.

The larger the values of the adhesion amount and the adhesion ratio, the better the liquid scattering prevention performance. Adhesion amount = [weight of contents adhered to metal plate] / [total amount of contents sprayed in 3 seconds] × 100 (%) Adhesion rate = [weight of contents adhered to metal plate] / [(3 seconds X) (the ratio of the stock solution in the contents)] x 100 (%) Table 1 shows the adhesion amount and the adhesion ratio thus determined.

Slip feeling of attached matter Each aerosol product was evaluated by the ratio (%) of 10 panelists who judged that a suitable sliding property and a good feeling of use were obtained by 10 panelists. Table 1 shows the evaluation results of the slipperiness of the attached matter.

Stability of Contents In order to evaluate the stability of contents, each aerosol product was stored in a constant temperature room at 40 ° C. for 1, 2 or 3 months, and the remaining amount of indomethacin as an active ingredient was measured. evaluated. Table 1 also shows the evaluation results of the stability.

Evaluation of Particle Size of the Deposits For evaluation of the particle size of the deposits, the average particle size of the deposits was measured. The results are shown in Table 1.

[0071]

[Table 1]

[0072]

As described above in detail with the embodiments, according to the aerosol composition for anti-inflammatory gel according to claim 1 of the present invention, scattering of indomethacin which is an active ingredient at the time of injection is suppressed, It is attached to the target site in the form of a gel, preventing dripping and improving the attachment rate.

Further, the stability of indomethacin as an active ingredient can be improved.

According to the aerosol composition for anti-inflammatory gel according to the second aspect of the present invention, the carboxyvinyl polymer is neutralized, and the scattering of indomethacin, which is an active ingredient at the time of injection, is suppressed, so that the gel is applied to the target site. In this manner, the liquid is prevented from dripping, and the adhesion rate can be improved.

Further, according to the aerosol composition for a flame-extinguishing gel according to the third aspect of the present invention, the aerosol composition for a flame-extinguishing gel according to the first or second aspect is further provided with an appropriate degree of slipperiness and spreadability. Can be imparted, and the feeling of use can be improved.

According to the invention described in each of the above claims, it is possible to produce an aerosol product containing indomethacin as an active ingredient.

Claims (3)

[Claims] (A) Indomethacin 0.75 to 1.0
% By weight, (B) carboxyvinyl polymer 0.01 to
A propellant comprising 100 parts by weight of a stock solution containing 2.0% by weight, (C) 10 to 60% by weight of alcohol and / or glycol, and (D) 35 to 89.24% by weight of water; An aerosol composition for an anti-inflammatory gel, comprising: parts by weight. 2. The method according to claim 1, wherein the stock solution contains (E) amines and / or
The aerosol composition for an anti-inflammatory gel according to claim 1, further comprising 0.01 to 2.0% by weight of a base. 3. The undiluted solution comprises (F) 0.1 to 10% by weight of an inorganic powder and / or an organic powder having a primary particle diameter of 0.1 to 50 μm. 3. The aerosol composition for anti-inflammatory gel according to 1 or 2.