JP2000198719A - Hair growing agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an external medicine preparation for hair growing and hair quality improving, manifesting enhanced hair growing action and improvement in quality of the grown hair, useful for therapeutic agent for male alopecia and alopecia areata by including minoxidil and panthenols as the principal components. SOLUTION: This preparation includes (A) minoxidil, (B) panthenols (e.g.; D-panthenol, L-panthenol, pantothenic acid, calcium pantothenate, and the like), as the principal components. It includes the component B in an amount of 0.02-10 times the weight of the component A, and preferably includes 1-10 g of the component A and 0.5-5 g of the component B per 100 mL of the preparation. The preparation includes, if necessary, several solvents, solubilzing agents, surfactants, antioxidants, emulsion stabilizers, gelling agents, propellants, and the like.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a minoxidil-containing external preparation for a hair growth agent containing minoxidil as a main component.

[0002]

2. Description of the Related Art Various types of hair such as head hair, beard, and body hair are found in the human body. Each hair is formed in a different place and at different times, and the hair cycle (the hair is in the elongation phase,
The cycle in which shedding occurs after the telogen phase and new hair elongates with it) is also different.
Each hair has its own unique shape.

Here, the shedding of hair growing on the human body may cause great trouble for the person.
For example, hair loss, which is considered to be inhibition of hair growth by male hormones, is called male pattern hair loss, and is actually a serious problem for many men.

[0004] By the way, male pattern hair loss is considered to be largely attributable to heredity. In addition, for example, circular hair loss is considered to be caused by stress, such as circular hair loss. It occurs without. Regarding such loss of hair, particularly with respect to loss of hair, a drug effective for regenerating hair from the state after hair loss has been studied in the past.

[0005] Regarding such medicines, irrespective of whether the hair loss is caused by an inborn factor or an acquired factor, minoxidil is effective as a medicine effective for regenerating hair from a state after hair loss. It has been known. For example, JP-A-63-166823 discloses a minoxidil-containing external preparation for a hair growth agent containing minoxidil as a main component. Further, it is disclosed that an activity enhancer, a vehicle, a softener, a solvent, a wetting agent, a thickener, a powder, and the like are appropriately added to the external preparation.

[0006]

However, with regard to the above-mentioned external preparation for hair growth drug containing minoxidil according to the prior art, a sufficient study on the optimum concentration of minoxidil was carried out.
Sufficient studies have not been conducted on the type of activity enhancer and the like and the optimum concentration.

The present invention has been made in view of the above circumstances, and it is an object of the present invention to provide an external preparation for a hair growth drug containing minoxidil, the optimum concentration of minoxidil, the type and the optimum concentration of an activity enhancer and the like contained therein. An object of the present invention is to provide a minoxidil-containing external preparation for hair growth drug which is superior to conventional products.

[0008]

Means for Solving the Problems As a result of intensive studies conducted by the present inventors to achieve the above object, the amount of minoxidil in an external preparation for hair growth medicine containing minoxidil was adjusted to an appropriate range. By adding an appropriate amount of panthenols to the appropriate amount of minoxidil, the hair growth effect of minoxidil can be significantly enhanced, and the hair quality of the hair that has grown by the action of minoxidil can be improved. And completed the present invention.

[0009] The inventors of the present invention have found that, for an external preparation for hair growth medicine containing minoxidil, the amount of minoxidil contained in 100 mL of the external preparation for hair growth medicine is improved with respect to enhancing the hair growth effect and improving the hair quality of the hair. The range of 1 g to 5 g (that is, the concentration of minoxidil is 1 w / v% to 5 w / v%), and the amount of panthenols contained in 100 mL of the external preparation for hair growth medicine is 0.1 g to 10 g (that is, 0.1 g to 10 g). , Minoxidil concentration of 0.1 w / v% to 10 w / v%) was found to be appropriate.

[0010] In this connection, if the concentration of minoxidil and the concentration of panthenols are adjusted within the above-specified range, the hair growth effect and the hair quality improving effect of the hair growth are stronger than before. In addition to being able to provide an excellent external preparation for hair growth medicine, it is also conceivable that an optimum value exists within the range. Therefore, within this range, the concentration of minoxidil and / or the concentration and type of panthenols may be appropriately adjusted. It is also within the scope of the present invention to adjust the strength of the hair growth effect and the improvement of the hair quality of the hair growth by the topical preparation for hair growth medicine containing minoxidil by changing.

In contrast to the invention in which panthenols are specified as an activity enhancer and the optimum concentration range is specified, for example, in the invention disclosed in JP-A-63-166823, Only three concentrations of 0.1 to 50% by weight, 0.5 to 25% by weight and 0.5 to 10% by weight are shown as the concentrations of the general activity enhancers, which are particularly preferred. Panthenols are not specified as an activity enhancer, much less the concentration of panthenols is specified.

More specifically, the present invention provides the following external preparations and methods.

(1) An external preparation for a hair-growing hair modifying drug which contains minoxidil and panthenols as main components and improves the hair quality of hair that has grown by the hair-growing action of minoxidil.

(2) An additive for improving the hair growth of a hair that has grown by the hair-growth action of minoxidil and containing a panthenol as a main component, for improving the hair quality of a hair that has been grown by minoxidil. .

(3) An external preparation for hair growth medicine containing minoxidil and panthenols as main components, and 0.02 to 10 times, preferably 0.1 to 10 times, of minoxidil.
An external preparation for a hair growth drug containing panthenol in a weight ratio of 1 to 10 times, more preferably 0.2 to 2 times.

(4) The external preparation for hair growth drug according to (3), wherein the amount of minoxidil in 100 mL of the external preparation for hair growth medicine is 1 g to 10 g.

(5) An external preparation for hair growth medicine containing minoxidil and panthenols as main components, which is 0.5 to 10 times (particularly 0.5 to 2 times) the panthenols. (3) An external preparation for hair growth medicine containing minoxidil in a weight ratio of (2).

(6) The external preparation for hair growth preparation according to (5), wherein the amount of panthenol in 100 mL of the external preparation for hair growth preparation is 0.1 g to 10 g.

(7) An external solution comprising the following components and other drug adjuvants added as needed.

[0020]

[Table 1]

(8) The dosage form is a liquid, cream, ointment, gel or aerosol (1)
The external preparation, enhancer or additive according to any one of (1) to (6).

(9) The panthenols are one or more selected from the group consisting of D-panthenol, L-panthenol, pantothenic acid and pantothenate (1) to (7) 3.) External preparations according to any of the above. The “pantothenate” is typically calcium pantothenate. In addition, "1 or 2
More than one species ", and may be in the form of, for example, DL-panthenol, which is a mixture of D-panthenol and L-panthenol, or a mixture of DL-panthenol and calcium pantothenate. .

(10) The external preparation according to (9), wherein the panthenol is D-panthenol.

(11) By adding panthenols to a minoxidil-containing external preparation for hair growth medicine containing minoxidil as a main component, the hair can be grown on the external preparation for hair growth medicine containing minoxidil by the hair growth action of minoxidil. A method of adding a hair modifying effect.

(12) A method for producing an external preparation which promotes hair growth of good quality hair by adding a predetermined amount of panthenol to an external preparation containing minoxidil as a main component and containing minoxidil as a main component.

(13) The amount of minoxidil in 100 mL of the external preparation for hair growth medicine is 1 g to 10 g (particularly, 1 g to 5 g).
g) minoxidil-containing external preparation for hair growth drug,
A method of adjusting the degree of improvement in the hair quality of hair that has grown by the hair growth action of minoxidil by adding panthenols in an amount of 0.1 g to 10 g (particularly, 0.5 g to 5 g).

(14) The weight ratio of the minoxidil-containing external preparation for hair growth medicine containing minoxidil as a main component is 0.02 to 10 times the weight ratio of the minoxidil contained in the external preparation for hair growth medicine containing minoxidil. By adding panthenols in the range of 0.1 times to 10 times, and more preferably in the range of 0.2 times to 2 times, the strength of the hair growth action of the minoxidil-containing external preparation for hair growth drug is increased. How to adjust.

(15) In an external preparation for hair growth medicine containing minoxidil and panthenols as main components, by changing the kind of the contained panthenols, the strength of the hair growth action of minoxidil and the hair growth of minoxidil are improved. A method of changing the degree of improvement in hair quality of hair that has grown by the action.

In the present specification, "contained as a main component" means that it is contained at a concentration which contributes to enhancement of the hair growth effect and improvement of the hair quality of the hair.

The term “adjustment” includes not only the case where the action is enhanced but also the case where the action is reduced in terms of enhancing the hair growth effect and improving the hair quality of the hair.

In the present specification, “hair growth” means
This includes the case where hair is grown and then hair is further grown.

The term "enhancing agent" or "activity enhancing agent" refers to an external preparation for minoxidil-containing hair growth agent containing an effective amount of minoxidil as a hair growth agent. It refers to a substance having the property of enhancing the hair growth effect of an external preparation.

"Hair growth hair modification" refers to, for example, increasing the water retention of hair that has grown by the action of minoxidil,
This means giving the hair a moist feeling and adjusting the color and rigidity of the hair as appropriate.

[0034]

BEST MODE FOR CARRYING OUT THE INVENTION The term "minoxidil solubilizing agent" serves as a solvent for minoxidil and dissolves water-insoluble minoxidil in an external preparation. Any substance can be used as long as it has an action of dissolving minoxidil in good harmony with other components in the external preparation, including a solubilizing agent. Minoxidil solubilizers typically include polyhydric alcohols, especially propylene glycol, dipropylene glycol, dibutylene glycol (eg, 1,3-butylene glycol), hexylene glycol, glycerin, polyethylene glycol, and the like. Can be.

The "viscosity modifier" is used to reduce the viscosity of the external preparation according to the present invention containing minoxidil and its solubilizing agent and panthenol. It is appropriately determined in consideration of the viscosity of panthenol and the like. A typical example of a viscosity modifier is ethanol.

Here, the "drug adjuvant" refers to, for example, L-menthol, glycyrrhetinic acid, tocopherol acetate and the like, such as "various solvents, solubilizing agents, surfactants, etc." This is a concept that includes various things.

<Various solvents, solubilizers, surfactants, etc.>
In the external preparation according to the present invention, the following can be blended as necessary, and, for example, a perfume or the like, a base component or the like usually used to obtain a desired dosage form, the present invention It can be blended within a range that does not impair the effect.

Various solvents (water, lower alcohols (methanol, ethanol (including denatured ethanol), isopropyl alcohol, etc.), etc.), solubilizers (medium or higher esters (diisopropyl adipate, isopropyl myristate, etc.), Medium-chain fatty acid triglycerides, fatty acid esters, various vegetable oils, various animal oils, polyhydric alcohol fatty acid esters, alkyl glyceryl ethers, hydrocarbons, pH adjusters (lactic acid, sodium hydroxide, etc.)
Etc.), surfactants (sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester,
Propylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbite fatty acid ester, polyoxyethylene glycerin fatty acid ester, 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, polyoxyethylene lanolin derivative, polyoxyethylene alkylamide, polyoxyethylene alkylamine, lecithin derivative, polymer emulsifier ), Antioxidants (dibutylhydroxytoluene, isopropylgallate, etc.), emulsion stabilizers (higher alcohols, etc.), gelling agents (water-soluble polymers, etc.),
Propellants (liquefied petroleum gas, dimethyl ether, nitrogen, oxygen, carbon dioxide, air, etc.).

[Application, Use and Treatment of External Preparation According to the Present Invention] The external preparation according to the present invention can be used in the form of a liquid, cream, ointment, gel or aerosol. Therefore, a method of treating hair loss by administering the external preparation of the present invention in these dosage forms as it is to a hair loss person is included in the scope of the present invention. In addition, more essentially, "a method for treating hair loss characterized by adding a predetermined amount of panthenols to a minoxidil-containing hair growth drug and then administering it to a hair loss person" is also included in the scope of the present invention. .

The external preparation according to the present invention must contain minoxidil and panthenols in the above-mentioned numerical ranges. And does not indicate an absolute critical range. Therefore, for example, when the content of minoxidil or panthenols is too small, no enhancement of hair growth effect and no improvement in hair quality of hair growth appear, or conversely,
In the case that these contents are too large and are no longer usable as external preparations,
In other cases, such as when the hair growth effect is enhanced or the hair quality of the hair growth is improved compared to a minoxidil-containing topical preparation for hair growth that acts substantially only with minoxidil alone It should be construed that even if the numerical value is slightly out of the above range, it is included in the scope of rights of the present invention as an equivalent range.

[0041]

According to the minoxidil-containing external preparation for hair growth drug containing the appropriate amount of minoxidil and the appropriate amount of panthenols as described above, the minoxidil is used as demonstrated in the examples below. And the hair quality of the hair that has grown is improved by the action of minoxidil. Therefore, the external preparation according to the present invention is extremely useful, for example, as a therapeutic agent for male pattern hair loss and circular hair loss.

[0042]

The present invention will be described more specifically with reference to the following examples and test examples. The following embodiments are merely examples of some specific examples included in the present invention, and the present invention is not limited to the following embodiments.

First, the sample 1 of the present invention was prepared according to the formulation shown in the following table.
-20 and control samples 1-5 were prepared. Preparation is carried out by stirring each component in the table according to a conventional method and dissolving them uniformly.
By setting it to L, external preparations according to the present invention samples 1 to 6 and control samples 1 to 5 were obtained.

[0044]

[Table 2]

[0045]

[Table 3]

[0046]

[Table 4]

[0047]

[Table 5]

[Test Example-"Hair-growth effect test"] Samples 1 to 5 of the present invention were formulated according to the formulation shown in Table 2 according to the preparation method of Example 1 described above.
6 and control samples 1-5 were prepared.

First, a group of 10 test animals (C3H / HeNCrJ mice (male, 7 weeks old)) was used, and a 2 cm × 3 cm area on the back of each animal was shaved with a clipper and a razor. Provided.

Next, samples 1 to 6 of the present invention and control samples 1 to
For each of No. 5, a separate test animal was allocated, and about 0.2 mL was applied to the depilated portion once a day. Then, the hair growth effect was evaluated based on the average number of days until the hair of the test part was completely regenerated. The application was continued until 60 days even if the hair was completely regenerated.

The results are shown in the following table. From these results, it was revealed that the hair growth effect was dramatically enhanced by the combination of minoxidil and a drug selected from "D-panthenol, DL-panthenol and calcium pantothenate".

[0052]

[Table 6]

[Test Example-"Measurement of Hair Water Retention Ability"]
Provided to test animals in the above test example "hair growth effect test",
For each animal 60 days after application, 5
% Polyoxyethylene (2) trimethylamine lauryl sulfate aqueous solution about 0.2 mL for 1 minute, then wash with warm running water until bubbles disappear, further wipe off excess water with absorbent cotton, remove hair with hair clipper did.

About 50 mg of the obtained hair was weighed and
The sample was stored under the conditions of 40 ° C. and 40% RH (Room Humidity), and the weight change over time was measured up to 24 hours. The moisture percentage at each measurement point was calculated from the weight at each measurement point according to the following equation 1.

[0055]

(Equation 1)

The water retention at each measurement point was calculated according to the following equation (2).

[0057]

(Equation 2)

The results of measuring the water retention are shown in the following table.

[0059]

[Table 7]

As is evident from the results shown in Table 7 above, the combined use of minoxidil and a drug selected from D-panthenol, DL-panthenol or calcium pantothenate synergistically enhances the hair moisture retention ability. ,
It lasts especially long.

Here, in light of the above two results, even among the same panthenols, there is a slight effect of D-panthenol, L-panthenol and calcium pantothenate on the effect of enhancing the hair growth effect of minoxidil. It seems that there is a difference (Comparing Example Sample 1 with Example Samples 3 and 5 in Table 6. Even though the content of panthenols is the same, the effect is slightly different due to the type of panthenols) . On the other hand, D-panthenol, L-panthenol and calcium pantothenate have almost the same effect on improving the hair quality of the hair.

[Stability Test] In conducting the stability test, the samples of Examples 7, 8 and 9 were filled in a polyethylene terephthalate container and sealed with a screw cap. Then, they are placed at 25 ° C. and 60% RH (Re
lative Humidity) for 9 weeks.

The results are shown in the following table.

[0064]

[Table 8]

From the results in the above table, it can be seen that the hair growth agent of the present invention containing minoxidil and panthenols as main components is stable.

Next, as a stability test, a test was conducted to determine whether panthenols can coexist stably in the hair growth agent of the present invention. In conducting the test, the sample was stored for 4 months without setting humidity in a state filled in a black polyethylene terephthalate airtight container.
The sample to be tested is the same sample at 5 ° C and 4 ° C.
Stored at 0 ° C.

The stability of panthenols in the hair growth agent according to the present invention was evaluated by measuring the amount of D-panthenol in the sample by the following high-performance liquid chromatography method.

[0068]

[Table 9]

The results are shown in the following table.

[0070]

[Table 10]

As shown in Table 10 above, 5 ° C. and 4 ° C.
No change was found in the amount of D-panthenol contained in any of the samples at a temperature of 0 ° C. Also,
Regarding the appearance, no change was observed in any of the samples even after storage for 4 months as compared with the time when the test was started.

As described above, D-panthenol in the example sample stored under the conditions of the accelerated test at 40 ° C.
Since it was stable even after storage for 4 months, it was proved that panthenols could coexist stably in the hair growth agent of the present invention. .

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification code FI Theme coat ゛ (Reference) A61K 31/506 A61K 31/506 47/16 47/16 A61P 17/00 A61P 17/00 17/14 17 / 14 // C07D 239/50 C07D 239/50 (72) Takako Okajima 3-24-1, Takada, Toshima-ku, Tokyo Inside Taisho Pharmaceutical Co., Ltd. (72) Fumiki Kimura 3-24 Takada, Toshima-ku, Tokyo No. 1 Taisho Pharmaceutical Co., Ltd.

Claims (6)

[Claims] 1. An external preparation for a hair growth-improving drug for improving hair quality of hair that has grown by the hair-growing action of minoxidil, comprising minoxidil and panthenols as main components. 2. An external preparation for hair growth medicine containing minoxidil and panthenols as main components, wherein the panthenols are contained in a weight ratio of 0.02 to 10 times that of minoxidil. External preparation for hair medicine. 3. The external preparation for hair growth medicine according to claim 1, wherein the amount of minoxidil in 100 mL of the external preparation for hair growth medicine is 1 g to 10 g. 4. The external preparation for a hair growth agent according to claim 1, wherein the amount of panthenol in 100 mL of the external preparation for a hair growth agent is 0.5 g to 5 g. 5. The dosage form according to claim 1, wherein the dosage form is any of a liquid, a cream, an ointment, a gel and an aerosol.
The external preparation, enhancer or additive according to any one of the above. 6. The panthenol is one or more selected from the group consisting of D-panthenol, L-panthenol, pantothenic acid and pantothenate. An external preparation according to item 1.