JPH1112136A - Minoxidil-formulated aerosol - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an aerosol capable of enabling minoxidil, which is an active ingredient, to surely reach the scalp. SOLUTION: This aerosol is prepared by forming a jetting form into a stream shape by regulating the amount ratio of a stock solution and a propellant, and valve opening, and further forming the liquid into a sherbet shape by regulating the composition of the stock solution. As the result, the loss of the active ingredient by dispersion is reduced, and the active ingredient is enabled to surely reach the scalp by a physical jetting pressure.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an aerosol formulation containing minoxidil as an active ingredient and capable of reliably spraying the active ingredient onto the scalp.

[0002]

2. Description of the Related Art Minoxidil (2,4-diamino-6), a drug which has been used as a therapeutic agent for hypertension in recent years.
-Piperidinopyrimidine-3-oxide) was found to have hirsutism as a side effect, and its use as a hair growth-promoting agent for male pattern hair loss and hirsutism has been studied. When applied to male pattern hair loss and rosacea, the blood pressure lowering effect, which is the original medicinal effect of minoxidil, becomes a problem as an unfavorable effect. Therefore, a method of direct administration to the scalp mainly using an external solution or an aerosol. Alternatively, the above problem is avoided by devising a dosage form.

[0003]

[0007] However, while the external liquid preparation has been effective in terms of the manifestation of medicinal effects and suppression of side effects, it is not always satisfactory in terms of feeling of use and prevention of bacterial contamination. In addition, although the aerosol is excellent in simplicity and sterility, it has problems such as inhalation of the atomized active ingredient and loss due to scattering into the atmosphere. Foams having a foaming property have also been developed, but have problems such as being blocked by the hair and making it difficult for the active ingredient to reach the scalp, and are not sufficient in terms of the hair growth effect. Thus, the development of a dosage form that can reliably provide an active ingredient to the scalp and has an excellent feeling upon use has been desired.

[0004]

Means for Solving the Problems In developing a hair growth agent containing minoxidil, the present inventors devised the injection properties of the aerosol to suppress the diffusion of minoxidil while maintaining the characteristics of the conventional aerosol, In addition, the inventors have found that an aerosol preparation having an improved hair growth effect with improved accessibility of minoxidil to the scalp can be prepared, and the present invention has been completed based on the findings. That is, the present invention is an aerosol formulation containing minoxidil, characterized in that the jetting properties are stream-like or sherbet-like.

In the present invention, the aerosol having a jetting property in a stream form means that the content jetted from an aerosol container does not become a mist and is diffused into the atmosphere, but the content becomes linear. Aerosol agent. An aerosol having a jetting property in the form of a sherbet means that the content sprayed from the aerosol container does not become a mist and is not diffused into the atmosphere, but the content is cooled at the time of spraying and a large particle size is obtained. Aerosol agent.

When minoxidil is sprayed onto the scalp using a stream-type or sherbet-type aerosol, the contents are not mist-like and the scattering of minoxidil is extremely small as in a conventional aerosol, regardless of the properties. Minoxidil loss to the atmosphere can be significantly reduced. In addition, since the physical injection pressure is higher than that of the atomized aerosol, minoxidil can effectively reach the scalp even in the hairy part.

Further, the scalp can be stimulated by physical pressure which cannot be obtained with a nebulized aerosol,
In addition, in the sherbet property, the blood flow in the scalp can be temporarily increased due to the rebound effect by cooling the application portion. Therefore, the initial percutaneous absorption rate of minoxidil is increased compared to the case where minoxidil is directly applied to the scalp, not to mention the atomized or foam-type aerosol having a low rate of reaching the scalp. The thing turned out. This means that the aerosol of the present invention is more excellent in hair growth effect than the conventional external preparation containing minoxidil. That is, when the stream-type or sherbet-type aerosol composition containing minoxidil of the present invention is used, the effect of temporarily increasing the blood flow can be easily obtained without massaging the scalp.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The amount of minoxidil in the present invention is desirably 0.1% by weight or more in a stock solution. If the amount is less than 0.1% by weight, the efficacy of minoxidil may not be sufficiently exerted even if the blood flow rate is increased by the aerosol of the present invention. In order to make the spray property of the aerosol agent into a stream, any conventionally used method can be used. For example, in a form in which a stock solution and a propellant, which have been used as one form of an aerosol, are sealed in the same chamber, the weight ratio of the stock solution and the propellant is the weight ratio, and the stock solution: propellant is 99.9: 0.1. ~ 4
0:60, more preferably 99.5: 0.5 to 50: 5
It may be adjusted to 0 and the flow path through which the contents reach the inside of the valve housing at the time of injection may be one path. The inside of the container is 2
A method in which a stock solution and a propellant are separated and sprayed using a double-structured container divided into chambers, and a stock solution is sealed in a rubber inner bag attached to the container, and the inner solution is used without using a propellant. It is also possible to form a stream using a method of injecting utilizing the contraction force of the bag.

Further, in order to form the jetting shape into a sherbet shape, any conventionally used method can be used. For example, a method in which water, a lower alcohol and a specific surfactant are blended (Japanese Unexamined Patent Publication No. No. 103526). As the injection pressure supply of the aerosol agent of the present invention, a commonly used liquefied gas such as liquefied petroleum gas, dimethyl ether, and chlorofluorocarbon, as well as a compressed gas such as nitrogen, oxygen, carbon dioxide, and air can be used. Further, as described above, a structure for supplying a physical pressure other than the gas pressure, such as a rubber inner bag in an aerosol container, may be used, and as a result, the jetting property becomes a stream-like or sherbet-like. Thus, the effects of the present invention can be obtained.

The following components can be added to the aerosol of the present invention at appropriate times in addition to flavors and pigments for the purpose of assisting the medicinal effect of minoxidil or adding other medicinal effects.

Vasodilator carpronium chloride, benzyl nicotinate, assembly extract, panax ginseng extract, vitamin E acetate,
Pepper tincture etc.Adrenal corticosteroids Hydrocortisone acetate, Hydrocortisone butyrate propionate, etc.Keratin softeners Urea, salicylic acid, etc.Humectants Sodium hyaluronate, chondroitin sulfate, Cordyceps sinensis extract, saffron extract, etc. Chlorpheniramine acid Anti-inflammatory drug Methyl salicylate, glycol salicylate, indomethacin, ibuprofen, flurbiprofen, diclofenac, felbinac, ketoprofen, dipotassium glycyrrhizinate, glycyrrhetinic acid, azulene derivative, etc. fungicide chlorhexidine gluconate, isopropylmethylphenol, No. 4 Grade ammonium salt, hinokitiol, etc. Antioxidant dibutylhydroxytol Down, isopropyl gallate, etc. fresheners menthol, peppermint oil, camphor As the component available for formulation in accordance with the formulation of these various ingredients include the following.

Base Water, lower alcohols such as methanol, ethanol, denatured ethanol and isopropyl alcohol Solubilizers Diisopropyl adipate, isopropyl myristate, 1.3-butylene glycol, propylene glycol, polyethylene glycol, glycerin, medium chain fatty acid triglyceride , Fatty acid esters, various vegetable oils, various animal oils, polyhydric alcohol fatty acid esters, alkyl glyceryl ethers, hydrocarbons, lactic acid, sodium hydroxide, etc. Surfactants sorbitan fatty acid esters, glycerin fatty acid esters, polyglycerin fatty acid esters, propylene glycol fatty acids Ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbite fatty acid ester, polyoxyethylene glycerin fatty acid Stele, polyethylene glycol fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, polyoxyethylene beeswax derivative, polyoxy Ethylene lanolin derivative, polyoxyethylene alkylamide, polyoxyethylene alkylamine, lecithin derivative, polymer emulsifier Emulsion stabilizer (higher alcohol etc.), gelling agent (polymer etc.), adhesive etc.

[0013]

According to the aerosol of the present invention, the loss due to the scattering of minoxidil can be suppressed and the minoxidil can efficiently reach the scalp. In addition, the initial percutaneous absorption rate of minoxidil can be increased by increasing the blood flow at the administration site.

[0014]

【Example】

<Example 1> Stream aerosol 100 g of aerosol stock solution sufficiently mixed with 1 g of minoxidil, 10 g of propylene glycol, and 89 g of ethanol.
55 g of this stock solution was charged into a pressure-resistant container for aerosol, and further charged with 45 g of dimethyl ether as a propellant, and then a valve and an actuator were attached to obtain a stream aerosol product.

Example 2 Sherbet-like aerosol Minoxidil 2 g, polyethylene glycol 5 g, isopropyl myristate 2 g, stearyl alcohol 3
g, 3 g of polyoxyethylene alkyl ether, 50 g of ethanol and 35 g of purified water are sufficiently mixed to prepare 100 g of an aerosol stock solution, 30 g of this stock solution is filled in a pressure-resistant container for aerosol, and liquefied petroleum gas 1 is further used as a propellant.
After filling with 5 g and 55 g of dimethyl ether, a valve,
An actuator was mounted to obtain a sherbet-like aerosol product.

<Example 3> Stream aerosol The following components were sufficiently mixed to prepare an aerosol stock solution.

Minoxidil 1.0 g Hinokitiol 0.01 g Glycyrrhetinic acid 0.2 g Poly (oxyethylene / oxypropylene) methylpolysiloxane copolymer 0.4 g 1,3-butylene glycol 1.0 g Polyoxyethylene hydrogenated castor oil 5 g Pantothenyl ethyl ether 0.2 g L-menthol 0.5 g DL-camphor 0.1 g peppermint oil 0.1 g eucalyptus oil 0.05 g clove oil 0.001 g jojoba alcohol 0.1 g assembly extract 0.05 g carrot extract 0.03 g Ethanol 50.0 mL Purified water Total 100 g Fill 50 g of this undiluted solution into a pressure-resistant container for aerosol, and further liquefy petroleum gas 10 g as a propellant and dimethyl ether 4
After filling with 0 g, a valve and an actuator were attached to obtain a stream aerosol product.

<Comparative Example 1> 1 g of minoxidil, 10 g of propylene glycol and 89 g of ethanol were uniformly mixed to prepare 100 g of a liquid preparation for external use.

<Comparative Example 2> 1 g of minoxidil, 10 g of propylene glycol, and 89 g of ethanol were sufficiently mixed to prepare 100 g of an aerosol stock solution, 30 g of this stock solution was filled in a pressure-resistant container for aerosol, and 30 g of liquefied petroleum gas as a propellant. And 40 g of dimethyl ether, and then a valve and an actuator were attached to prepare a mist aerosol.

Comparative Example 3 1 g of minoxidil, 5 g of propylene glycol, 5 g of ethanol, 4 g of squalane,
1.5 g of cetanol, glycerin monostearate 1
g, polyoxyethylene sorbitan monooleate 3
g, 1.5 g of sorbitan monooleate, 2 g of polyoxyethylene lanolin and 76 g of purified water are sufficiently emulsified and mixed to prepare 100 g of an aerosol stock solution. 95 g of this stock solution is filled in a pressure-resistant container for aerosol, and further liquefied as a propellant. After filling with 5 g of petroleum gas, a valve and a spout were attached to obtain a foamed aerosol product (foam).

<Test Example 1> Using Examples 1 to 3 and Comparative Example 1, 30 subjects were subjected to a usability test. There are a wide variety of items such as ease of administration and sensation, and the items to be emphasized differ depending on the individual. I got it. The rating is extremely good -7 points, good -6 points, fairly good -5 points, ordinary -4 points, slightly bad -3 points, bad -2.
Points, extremely bad-1 point, and evaluated by the number of people who scored 6 points or more.

The results are shown in Table 1.

[0023]

[Table 1]

<Test Example 2> Examples 1-3 and Comparative Example 2,
3 as a sample, Wistar rats (7-10 weeks old, n
= 3, a total of 15 animals).
Sprayed for seconds. Ten minutes after the injection, the abdomen was shaved with a shaver, and the exposed abdominal skin was wiped with alcohol-containing absorbent cotton. The amount of minoxidil in the absorbent cotton and the sample after the injection was quantified, and the amount of minoxidil reaching the abdominal skin and the amount of the minoxidil injected were determined.

The results are shown in Table 2.

[0026]

[Table 2]

<Test Example 3> Examples 1 to 3 and Comparative Example 1
2 as a sample, and administered to the right forearm of 10 male subjects,
Laser Doppler blood flow meter (PeriFl
ux System 4000: manufactured by Eurotech Japan Ltd.). The subject entered a room maintained at a constant temperature and humidity (temperature 23 ° C., relative humidity 60%) in order to obtain a steady state blood flow, then undressed his upper body and waited. One hour after the subject undressed, it was confirmed that the blood flow was in a steady state in the room, and measurement was started. In addition, since minoxidil itself affects the blood flow, the measurement time was completed in 30 minutes so that there was no influence of the drug, and evaluation was made based on the change rate of the blood flow during that time. The evaluation was made when the blood flow increased by 20% or more.
The case where the increase is 0% or more is represented by Δ, and the case where the increase in blood flow is less than 10% is represented by x. Table 3 shows the results.

[0028]

[Table 3]

From the results of Test Example 1, Test Example 2 and Test Example 3, the present invention reliably reaches the target site and increases the blood flow, so that the side effect of minoxidil can be suppressed and the combined effect can be expected. It was further confirmed that the feeling of use was excellent.

Claims (1)

[Claims] 1. An aerosol formulation containing minoxidil, characterized in that the spraying property is a stream or sherbet.