JP4442912B2 - Composition for external use - Google Patents

Description

  The present invention relates to a composition for external use in which the stability of adenosine having an excellent hair growth effect and blood circulation promoting effect is improved at low temperatures.

  Adenosine has been incorporated into hair-growth agents, skin external preparations, and the like as components that exhibit excellent hair-growth and blood circulation promoting effects on the scalp and hair and on the skin (Patent Documents 1 to 9). However, adenosine has a problem in solubility in water and alcohol, and the temperature dependence of the solubility is strongly recognized. Even if it is dissolved at high temperature or room temperature, it becomes supersaturated at low temperature, and precipitates over time.・ Precipitation is observed. Therefore, at present, the amount of practical adenosine blended at the product level is at most about 0.8% by mass of the product, and a means for blending adenosine at a level exceeding this is required. In addition, although the following patent documents 1-9 disclose the example which mix | blended 1% or more of the composition with adenosine, all are the mixing | blending at normal temperature (about 25 degreeC), and low temperature (5--20 degreeC). ) There is no example in which adenosine is blended at 1% or more.

Adenosine such as adenosine phosphate can be used in the form of a salt, so that a relatively large amount of the compound itself can be formulated (for example, Patent Document 4). However, a salt of adenosine exists in hair papilla cells and the like. Since the direct action on the adenosine receptor is reduced, it is difficult to exert a pharmacological effect that is originally expected for adenosine and that is commensurate with the amount of the adenosine receptor. Moreover, although the example (Example 2 of patent document 7) which mix | blended 10% adenosine with the application of the applicant of this application is also disclosed, this is the thing for which the dissolved state of adenosine is maintained only in a short time, It is not suitable for use over time. The test drug of the Example of the said patent document 7 is repeatedly prepared during the hair restoration test period.
Japanese Patent No. 2937446 Japanese Patent No. 3798927 JP 2001-288048 A JP 2001-288045 A JP 2001-288042 A JP 2001-288043 A JP 2001-288046 A JP 2001-288047 A JP 2004-143184 A

  The problem to be solved by the present invention is to provide means for making adenosine having excellent efficacy as described above a state in which stability over time is ensured even under low temperature conditions.

  As a result of intensive studies aimed at solving the above problems, the present inventor has found that adenosine, a cationic polymer having a molecular weight of 80,000 to 5,000,000 and a cationic monomer ratio of 10 to 100% by mass, a lower alcohol, In addition, by coexisting an organic acid in a specific mass range, even when adenosine is blended at a high concentration of 1 to 2% with respect to the composition, the solubility when preparing the product is good. The present invention was completed by finding that the stability of the product over time under low temperature conditions is ensured.

That is, this invention is an invention which provides the external composition (henceforth this composition) which has the characteristics of following (1)-(4).
(1) Adenosine is contained in an amount of 1.0 to 2.0% by mass based on the entire composition.
(2) A cationic polymer having a molecular weight of 80,000 to 5,000,000 and a cationic monomer ratio of 10 to 100% by mass is contained in an amount of 0.001 to 5% by mass of the entire composition.
(3) 35.0-65.0 mass% of ethanol, methanol, ethylene glycol, or isopropyl alcohol of the whole composition is contained.
(4) Contains an organic acid.

  This composition can be used as an external composition for the purpose or form in which adenosine is blended and its effect can be utilized on the skin or scalp and hair. Specifically, a composition for scalp and scalp hair (typically a hair restorer) with an excellent hair growth effect of adenosine, a skin external preparation that can also exhibit an excellent blood circulation promoting effect, and the like can be mentioned.

  According to the present invention, the composition for external use can be stored for a long period of time even under a low temperature condition while blending a high concentration of adenosine in the composition for external use (1.0 to 2.0% by mass of the whole composition).

[Composition ingredients of this composition]
One of the essential components of this composition is adenosine to be blended as an active ingredient. Adenosine is one of ribonucleosides and contains adenine which is a purine derivative in the base part.

  As adenosine to be blended in the present composition, a commercially available reagent can be used. The compounding quantity of adenosine in this composition is 1.0-2.0 mass% of the whole composition. The blending of less than 1.0% by mass is also possible, but other compositions can exhibit the same low temperature storage stability as the present composition, and the formulation advantages of the present composition are not fully manifested. . Moreover, when it exceeds 2.0 mass%, there exists a tendency for it to become difficult to fully suppress precipitation of adenosine at low temperature.

  In the present composition, one or more cationic polymers having a molecular weight of 80,000 to 5,000,000 and a cationic monomer ratio of 10 to 100% by mass are blended. If the molecular weight is less than 80,000, precipitation of adenosine at a low temperature cannot be sufficiently suppressed, and if it exceeds 5 million, the polymer feels strong in usability, which is not preferable.

  Examples of such cationic polymer include polydimethylmethylenepiperidinium chloride, dimethyldiallylammonium chloride / acrylamide copolymer, O- [2-hydroxy-3- (trimethylammonio) propyl] hydroxyethylcellulose chloride, Examples thereof include vinylpyrrolidone / N, N-dimethylaminoethyl methacrylate / stearyl acrylate / tripropylene glycol diacrylate copolymer, vinylpyrrolidone / N, N-dimethylaminoethyl methacrylate copolymer diethyl sulfate, and the like. The blending amount of the cationic polymer in the present composition can be appropriately selected depending on the kind of the cationic polymer and the like, and is preferably blended in an amount of 0.001 to 5.0% by mass of the entire composition. When the blending amount of the cationic polymer is less than 0.001% by mass of the whole composition, the effect of further improving the low temperature stability of adenosine by blending the cationic polymer tends to be insufficient. When the blending amount exceeds 5% by mass, the stickiness and film feeling at the time of drying become remarkable, and there is a tendency to cause problems in usability.

  Commercially available products of the above cationic polymers include, for example, Marcote 100 (manufactured by CALGON Co.), Marquat 550 (manufactured by CALGON Co.), CG polymer (manufactured by Osaka Organic Chemical Industry Co., Ltd.), Guff Coat 755-S (Nihonsei) Chemical JR), polymer JR-400 (Union Carbide Japan Co., Ltd.) and the like.

  Examples of the lower alcohol to be blended in the present composition include ethanol, methanol, ethylene glycol, isopropyl alcohol, etc., but it is preferable to use ethanol from the viewpoints of safety and practicality. Commercially available products include general alcohol 95-degree synthesis (Japan Alcohol Sales Co., Ltd.) and the like. The compounding quantity of lower alcohols, such as ethanol in this composition, is 35.0-65.0 mass% of the whole composition, and is 40.0-60.0 mass% suitably. If the blending amount is less than 35.0% by mass of the whole composition, precipitation of adenosine at a low temperature is observed, and if it exceeds 65.0% by mass, the solubility of adenosine is lowered. In addition, the compounding quantity of the lower alcohol in this specification and a claim is displayed as 100% alcohol conversion.

  The organic acid to be blended in the composition can be appropriately selected from those conventionally blended as an organic acid in a composition for external use, malic acid, citric acid, lactic acid, glutamic acid, pyrrolidone carboxylic acid, formic acid, Examples include acetic acid, benzoic acid, benzenesulfonic acid, and succinic acid. It is preferable to mix | blend the compounding quantity in this composition of organic acid in 0.0001-1.0 mass% of the whole composition. When the blending amount is less than 0.0001% by mass, the solubility of adenosine is not sufficiently good. When the blending amount exceeds 1.0% by mass, the stickiness during use and the irritation to the scalp tend to be remarkable. Is recognized.

  Examples of commercially available organic acids include DL-malic acid fuso S (manufactured by Fuso Chemical Co., Ltd.), oxalic acid (manufactured by Takeda Kirin Foods Co., Ltd.), lactic acid first grade (manufactured by Daiichi Pharmaceutical Co., Ltd.), L for cosmetics -Glutamic acid (Ajinomoto Co., Inc.) etc. are mentioned.

[Form of the present composition]
As described above, the main forms of the present composition include a scalp hair composition represented by a hair-growth material utilizing the hair-growth effect of adenosine, and a topical skin preparation utilizing the blood circulation promoting effect.

(1) Composition for scalp and hair (hereinafter also referred to as composition for scalp and hair)
In general, the causes of hair loss include activation of male hormones in organs such as hair follicles and sebaceous glands, decreased blood flow to hair papilla and hair follicles, excessive secretion of sebum, abnormalities of the scalp due to the production of peroxides, Malnutrition is considered.

  For this reason, the conventional hair restorer generally contains a component having an action of removing or reducing these causes. Among them, adenosine has an excellent blood circulation promoting effect, and in combination with this blood circulation promoting effect, an excellent hair growth action such as a hair loss preventing action and a hair growth promoting action is recognized. Currently, adenosine is actively blended in compositions for scalp and hair, such as hair growth agents.

  By making this composition into a composition for scalp and scalp hair, by containing a high concentration of adenosine of 1.0 to 2.0% by mass of the whole composition, blood circulation in the scalp is reduced due to its excellent blood circulation promoting effect. It is possible to obtain a composition for scalp and hair that is promoted, exhibits a hair loss preventing action, a hair growth promoting action, etc., and has excellent temporal stability at low temperatures.

  In the present invention, “hair growth” is used in a concept including a hair loss preventing effect, a hair growth promoting effect and the like.

  In the composition for scalp and scalp hair, a hair-restoring ingredient that can generally be blended in the composition for scalp and hair can be blended in a range that does not clearly impair the low-temperature stability effect and the effect of adenosine according to the present invention.

  For example, as an antibacterial agent, hinokitiol, hexachlorophene, benzalkonium chloride, cetylpyridinium chloride, undecylenic acid, trichlorocarbanilide, bithionol, and the like can be blended.

Further, as drug components, nicotinamide, benzyl nicotinate, vitamin E or derivatives thereof, for example, vasodilators such as vitamin E acetate, assembly extract, carpronium chloride, acetylcholine derivatives; skin function enhancers such as cephalanthin; glycyrrhetic acid or Derivatives, anti-inflammatory agents such as purple root extract; female hormone agents such as estradiol and estrone; amino acids such as serine, methionine, and arginine; vitamins such as vitamin A, vitamin B ₁ , vitamin B ₆ , biotin, pantothenic acid, and derivatives thereof Kinds: Nucleic acids such as adenine, cytosine, thymine and guanine can be blended.

  Furthermore, if necessary, a chemical such as salicylic acid, zinc or a derivative thereof, a lactic acid alkyl ester, or a refreshing agent such as menthol can be blended.

  Furthermore, 1 or more types of moisturizers can be mix | blended as needed. Examples of sugar humectants include glycerin, diglycerin, tetrose, pentose, hexose, heptose, tetrit, pentite, hexit, erythritol, maltitol, mannitol, sorbitol, xylitol, hyaluronic acid, polyoxyethylene methyl glucoside, etc. It is done. Examples of the humectant other than the sugar-type humectant include propylene glycol, dipropylene glycol, polyethylene glycol, butylene glycol, polybutylene glycol, and polyoxyethylene-polyoxypropylene-dimethyl ether. It is preferable that the content of the sugar-based moisturizing agent in the moisturizing agent is 25.0 to 100% by mass of the entire moisturizing agent.

  In addition to the various components described above, the present scalp and hair composition usually contains other components that can be blended in the composition for external use as long as the low-temperature stability effect and the efficacy of adenosine according to the present invention are not clearly impaired. For example, an oil, a surfactant, a thickener, an ultraviolet absorber, an antioxidant, a preservative, a fragrance, a pigment, water, and other solvents can be appropriately blended as necessary.

  The composition for scalp and scalp hair can be produced by a conventional method according to the intended dosage form. The dosage form which can be taken is arbitrary, for example, any liquid dosage form can be applied for external use such as liquid, emulsion, ointment, cream, gel, aerosol and the like. Moreover, the product form is also arbitrary, for example, it can be used in the form of a tonic, a scalp treatment, or a scalp lotion.

(2) External preparation for skin In addition to the above-mentioned composition for scalp and hair, this composition can be used as an external preparation for skin. That is, a skin external preparation that exhibits its excellent blood circulation promoting action sufficiently on the skin and has improved low-temperature stability by providing a high concentration of adenosine is provided.

  In the external preparation for skin, other components that can be generally blended in the composition for external use can be blended as needed within a range that does not clearly impair the low-temperature stability effect and the effect of adenosine according to the present invention. For example, necessary from among the above-mentioned antibacterial agents, drug components, refreshing agents, humectants, oils, surfactants, thickeners, UV absorbers, antioxidants, preservatives, fragrances, pigments, water and other solvents. Can be appropriately blended depending on

  The said external preparation for skin can be manufactured by a conventional method according to the target dosage form. The dosage form which can be taken is arbitrary, for example, any liquid dosage form can be applied for external use such as liquid, emulsion, ointment, cream, gel, aerosol and the like. Moreover, the product form is also arbitrary.

  Next, the present invention will be described more specifically with reference to examples. However, the scope of the present invention is not limited only to these examples. In addition, in the following Examples, a compounding quantity is the mass% with respect to the compounding object, and about adenosine, it is displayed as a solid content.

[Examples 1-11, Comparative Examples 1-11]
In the formulations shown in Tables 1 to 3, hair growth preparations were prepared based on the following production method, and further, the following tests revealed that these scalp and hair lotions had adenosine solubility (25 ° C.) and stable at 0 ° C. The sex was examined. The test results are also shown in Tables 1 to 3.

〔Production method〕
A perfume was dissolved in ethanol (ethanol part). Next, an organic acid and a cationic polymer were dissolved in purified water, and after adding this to the ethanol part, adenosine was added and stirred to obtain a transparent liquid lotion. Up to this point, the test was performed at 25 ° C. In addition, about the comparative example which was not able to melt | dissolve adenosine, the liquid was heated (30-50 degreeC) and once dissolved.

[Test methods and evaluation criteria]
The above manufacturing process is performed at room temperature (under 25 ° C.). At that time, those in which adenosine is completely dissolved are evaluated as “◯”, and a part of adenosine remains undissolved and completely dissolved. Was evaluated as “Δ” for those that required reheating, and “x” for those that did not dissolve most of the adenosine but required reheating for complete dissolution.

  In addition, the test product in which adenosine was completely dissolved in this manner was sealed in a vial with a lid, and allowed to stand at 0 ° C. for 1 month, and the precipitation of adenosine crystals after 1 month was measured at the start of the test. Similarly, it was evaluated as “◯” when adenosine was dissolved without any change, and evaluated as “△” when a slight amount of adenosine crystals were precipitated, so that the precipitation of adenosine crystals can be discriminated at a glance. Things were evaluated as “x”. These evaluation results are also shown in Tables 1 to 3.

  From the results in Table 1, it was possible to dissolve at room temperature up to 1.5% by blending polymer JR, and the stability over time at low temperature was also good up to 2.0% adenosine.

  From the results shown in Table 2, adenosine precipitation was observed at low temperatures in cationic monomolecules and cationic polymers with low molecular weight (80,000 or less), but other cationic polymers have good stability over time at low temperatures. Met. In all examples, the solubility of adenosine at 25 ° C. was good “◯”.

  From the results of Table 3, the low temperature stability could not be improved for the anion and nonionic polymers, and the low temperature stability with time was good only when the cationic polymer was blended.

From the results of Table 4, the solubility and low-temperature stability of adenosine deteriorated when the amount of alcohol was too much or too little. In addition, the comparative example 14 described in Table 4 was deleted by the procedure amendment after application.

  From the results of Table 5, adenosine improves the solubility and stability by blending polymer JR-400, but when it exceeds 5%, stirring and dissolution becomes difficult and cannot be completely dissolved.

  From the results shown in Table 6, the solubility and low-temperature stability of adenosine could be improved with various organic acids.

  Hereinafter, the formulation example of this invention is described as an Example. In these formulation examples, adenosine was stably dissolved for a long time even at a low temperature.

[Example 23] Hair restorer
Compounding component amount (% by mass)
Ethanol 60.0
Dipropylene glycol 6.0
Citric acid 0.05
Sodium citrate 0.1
Menthol 0.3
Vitamin E acetate 0.3
Adenosine 2.0
Marcote 550 (manufactured by CALGON Co.) 0.3
Purified water residue <Production method>
A fragrance | flavor and a chemical | medical agent were dissolved in ethanol (ethanol part). Next, an organic acid and a cationic polymer were dissolved in purified water, and after adding this to the ethanol part, adenosine was added and stirred to obtain a transparent liquid hair restorer.

[Example 24] External preparation for skin
Compounding component amount (% by mass)
Butylene glycol 8.0
Polyoxyethylene hydrogenated castor oil 0.5
Ethanol 35.0
Liquid paraffin 2.0
Carbomer 0.4
2-Amino-2-methyl-1-propanol 0.1
Adenosine 1.4
Polymer JR-400 1.0
(Made by Union Carbide Japan Co., Ltd.)
Perfume Appropriate amount of purified water residue <Production method>
The carbomer was dissolved in purified water, and an emulsified part made using an activator, purified water, and oil was added and stirred. To this was added ethanol and purified water in which fragrance was dissolved up to 50 ° C. to dissolve adenosine, and finally the carbomer was neutralized and thickened to obtain a skin external preparation.

[Example 25] Lotion
Compounding component amount (% by mass)
Butylene glycol 4.0
Hydroxypropyl cellulose 1.0
Ethanol 40.0
Adenosine 1.6
CG polymer (Osaka Organic Chemical Industry Co., Ltd.) 0.1
Perfume Appropriate amount of purified water residue <Production method>
A perfume was dissolved in ethanol (ethanol part). Next, an organic acid, a cationic polymer, and hydroxypropyl cellulose are dissolved in purified water, and after adding this to the ethanol part, adenosine is added and stirred to obtain a slightly thick transparent liquid. Got lotion.

Claims (5)

An external composition having the following features (1) to (4).
(1) Adenosine is contained in an amount of 1.0 to 2.0% by mass based on the entire composition.
(2) A cationic polymer having a molecular weight of 80,000 to 5,000,000 and a cationic monomer ratio of 10 to 100% by mass is contained in an amount of 0.001 to 5% by mass of the entire composition.
(3) 35.0-65.0 mass% of ethanol, methanol, ethylene glycol, or isopropyl alcohol of the whole composition is contained.
(4) Contains an organic acid. In the composition for external use, the cationic polymer in (2) is polydimethylmethylenepiperidinium chloride, dimethyldiallylammonium chloride / acrylamide copolymer, O- [2-hydroxy-3- (trimethylammonio) propyl chloride. ] Hydroxyethyl cellulose, vinylpyrrolidone / N, N-dimethylaminoethyl methacrylate / stearyl acrylate / tripropylene glycol diacrylate copolymer, and vinylpyrrolidone / N, N-dimethylaminoethyl methacrylate copolymer diethyl sulfate The composition for external use according to claim 1, wherein the composition is one or more selected from the group consisting of: In the external composition, the organic acid in (3) is selected from the group consisting of malic acid, citric acid, lactic acid, glutamic acid, pyrrolidone carboxylic acid, formic acid, acetic acid, benzoic acid, benzenesulfonic acid , and succinic acid. The composition for external use according to claim 1 or 2, wherein the composition is a seed or more. The composition for external use according to any one of claims 1 to 3, which is an composition for external use for scalp and hair. The composition for external use according to claim 4, wherein the composition for scalp and hair is a hair-growth material.