JP2008247752A - Composition for external application - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a means for ensuring, even under a low-temperature condition, the aging stability of adenosine having excellent drug action as a skin care preparation or an external agent for scalp and hair. <P>SOLUTION: The invention provides an external application composition having the following characteristics (1) to (3): (1) the composition contains adenosine in an amount of 1.0-2.0 mass% based on the total composition: (2) the composition contains a moisturizer in an amount of 10.0-20.0 mass% based on the total composition, and the content of a sugar-based moisturizer in the total moisturizer is 20.0-100 mass%: and (3) the composition contains a lower alcohol in an amount of 35.0-65.0 mass% based on the total composition. The use of the external composition for the treatment of the scalp or the hair is one of preferable embodiments of the invention. <P>COPYRIGHT: (C)2009,JPO&INPIT

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.

In addition, a relatively large amount of blending itself is possible by making adenosine such as adenosine phosphate into a salt form (for example, Patent Document 4), but adenosine salt 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 made adenosine, a humectant containing a sugar-type humectant at a certain ratio or more, and a lower alcohol coexist in a specific mass range. Thus, even when adenosine was blended at a high concentration of 1 to 2% with respect to the composition, it was found that the stability over time under low temperature conditions was ensured, and the present invention was completed.

That is, this invention is an invention which provides the external composition (henceforth this composition) which has the characteristics of following (1)-(3).
(1) Adenosine is contained in an amount of 1.0 to 2.0% by mass based on the entire composition.
(2) The humectant contains 10.0 to 20.0 mass% of the entire composition, and the content of the sugar-based humectant in the humectant is 25.0 to 100 mass% of the entire humectant.
(3) 35.0-65.0 mass% of lower alcohol is contained of the whole composition.

  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, long-term storage is possible even under low temperature conditions while blending a high concentration of adenosine in the composition for external use (1.0 to 2.0 mass% of the entire 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 kinds of humectants are blended in the range of 10.0 to 20.0% by mass, preferably 10.0 to 15.0%, and the humectant in the humectant. The content of the sugar-based humectant is 25.0 to 100% by mass, preferably 25.0 to 50.0%, based on the entire humectant. When the blending amount of the humectant is less than 10.0% by mass of the entire composition, the solubility of adenosine is not sufficiently improved, and precipitation of adenosine at a low temperature tends to be observed. When the content exceeds 20.0% by mass, the stickiness after use and drying of the composition becomes remarkable, and a tendency to cause problems in usability is recognized.

  The sugar-type humectant to be blended in the present composition may be one or more, and may be any of monosaccharides, oligosaccharides, and polysaccharides, such as glycerin, diglycerin, tetrose, pentose, hexose, heptose, tetrit, Examples include pentite, hexit, erythritol, maltitol, mannitol, sorbitol, xylitol, hyaluronic acid, polyoxyethylene methyl glucoside and the like. In addition, as moisturizers other than sugar-based moisturizers, propylene glycol, dipropylene glycol, polyethylene glycol, butylene glycol, polybutylene glycol, polyoxyethylene-polyoxypropylene-dimethyl ether, and the like as conventional moisturizers. What is mix | blended can be selected suitably.

  Examples of suitable moisturizer combinations in the present composition include dipropylene glycol, which is a moisturizer other than sugar moisturizer, and sorbitol, maltitol, polyoxyethylene methyl glucoside, etc., which are sugar moisturizers. One or more selected combinations may be mentioned. In this combination, it is preferable that dipropylene glycol is 0 to 75.0% by mass of the entire humectant, and particularly preferably 50.0 to 75.0%. Mixing such a combination of humectants with the present composition improves the solubility of adenosine in the base and increases the effect of suppressing precipitation of adenosine at low temperatures. Commercially available products of these moisturizers include dipropylene glycol (Asahi Denka Kogyo Co., Ltd.), sorbitol F (Niken Chemical Co., Ltd.), Marvit (Hayashibara Biochemical Laboratories), Glucam E-10 (Amacoal Corp.) Etc.

  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.

  In the present composition, one or more cationic polymers can be blended for the purpose of further improving the low temperature stability. The cationic polymer can be appropriately selected from those conventionally blended as a cationic polymer in an external composition. Examples include vinylpyrrolidone / N, N-dimethylaminoethyl methacrylic acid copolymer diethyl sulfate, dimethyldiallylammonium chloride / acrylamide copolymer, polydimethylmethylenepiperidinium chloride, O- [2-hydroxy-3 chloride]. -(Trimethylammonio) propyl] hydroxyethyl cellulose, vinylpyrrolidone / N, N-dimethylaminoethyl methacrylic acid copolymer diethyl sulfate solution, O- [2-hydroxy-3- (trimethylammonio) propyl] guar gum chloride, 2-methacryloyloxyethyl phosphorylcholine / 2-hydroxy-3-methacryloyloxypropyltrimethylammonium chloride copolymer, O- (2-hydroxy-3- (trimethylammonio) propyl) locust bean gum, Of Hidorokishipuropirutorimoniumu starch, vinylpyrrolidone-methacrylate N, N-dimethylaminoethyl acrylate stearyl diacrylate tripropylene glycol copolymer, 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.

  Examples of commercially available cationic polymers include CG polymer (Osaka Organic Chemical Co., Ltd.), PDM polymer (Osaka Organic Chemical Co., Ltd.), Guff Coat 755-S (Nippon Seika Co., Ltd.), Polymer JR- 400 (manufactured by Union Carbide Japan Co., Ltd.), Labor gum CG-M (Dainippon Pharmaceutical Co., Ltd.), Lipidure C (manufactured by Nippon Oil & Fats Co., Ltd.) and the like.

  The solubility of adenosine can be further improved by adding one or more organic acids to the composition. Examples of the organic acid 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, acetic acid, benzoic acid Acid, benzenesulfonic acid, succinic acid, benzenesulfone and the like can be mentioned. 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 effect of improving the solubility of adenosine due to the blending of the organic acid is not sufficiently exerted, and when exceeding 1.0% by mass, stickiness during use, There is a tendency for irritation to the scalp.

  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 skin external 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; glycyrrhetinic 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 or 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.

  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, as necessary from among the above-mentioned antibacterial agents, drug components, refreshing agents, oils, surfactants, thickeners, ultraviolet absorbers, antioxidants, preservatives, fragrances, pigments, water and the like. It can mix | blend suitably.

  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 1-17, Comparative Examples 1-11]
In the formulations shown in Tables 1 to 5, hair growth preparations were prepared according to the following production method, and further, the following tests showed that these scalp and hair lotions had adenosine solubility (25 ° C.) and low-temperature stability at 0 ° C. It was investigated. The test results are also shown in Tables 1 to 5.

〔Production method〕
A humectant and a fragrance were dissolved in 95% ethanol (ethanol part). Next, an organic acid, a dye, 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 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”. In addition, those having a short dissolution time and improved solubility were evaluated as “◎”. These evaluation results are also shown in Tables 1 to 5.

  From the results shown in Table 1, 1.6% adenosine could be dissolved in the range of 45 to 65% alcohol, and the low-temperature stability was good.

  From the results shown in Table 2, 1.7% adenosine can be easily dissolved by adding an organic acid such as lactic acid, malic acid or citric acid, and the stability over time at low temperature is also good. Became clear. In addition, when an inorganic acid such as phosphoric acid is added, the low-temperature stability is rather deteriorated.

  From the results in Table 3, polyol-type humectants such as dipropylene glycol cannot increase the solubility of adenosine, and 1.6% of adenosine can be dissolved by combining with sugar-type humectants such as sorbitol and maltitol. Also, the stability over time at low temperature was good.

  From the results of Table 4, the total amount of humectant was within a range of 10% to 20%, and adenosine could be sufficiently dissolved, and precipitation at low temperature was not observed.

  From the results shown in Table 5, 2% adenosine can be dissolved by adding a cationic polymer and combining with a sugar-type humectant such as sorbitol and dipropylene glycol, and the stability over time at low temperature was also good.

  Hereinafter, the formulation example of this invention is described as an Example. In these 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 8.0
Mabit 4.0
Citric acid 0.05
Sodium citrate 0.1
Menthol 0.3
Vitamin E acetate 0.3
Adenosine 2.0
PDM polymer (Osaka Organic Chemical Industry Co., Ltd.) 1.2
Purified water residue <Production method>
A fragrance | flavor and a chemical | medical agent were dissolved in ethanol (ethanol part). Next, a moisturizer, organic acid and 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 15.0
Sorbitol 5.0
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
Glutamic acid 0.01
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)
Dipropylene glycol 7.5
Maltitol 2.5
Hydroxypropyl cellulose 1.0
Ethanol 40.0
Adenosine 1.6
CG polymer (Osaka Organic Chemical Industry Co., Ltd.) 0.1
Lactic acid 0.02
Sodium lactate 0.12
Perfume Appropriate amount of purified water residue <Production method>
A perfume was dissolved in ethanol (ethanol part). Next, in the purified water, moisturizer, organic acid and cationic polymer, hydroxypropyl cellulose are dissolved, and after adding this to the ethanol part, adenosine is added and stirred to make it slightly thick A clear liquid lotion was obtained.

Claims (7)

An external composition having the following features (1) to (3).
(1) Adenosine is contained in an amount of 1.0 to 2.0% by mass based on the entire composition.
(2) The moisturizer is contained in an amount of 10.0 to 20.0 mass% of the entire composition, and the content of the sugar-type moisturizer in the moisturizer is 20.0 to 100 mass% of the entire moisturizer.
(3) 35.0-65.0 mass% of lower alcohol is contained of the whole composition. In the composition for external use, the sugar-based humectant in (2) is glycerin, diglycerin, tetrose, pentose, hexose, heptose, tetrit, pentite, hexit, erythritol, maltitol, mannitol, sorbitol, xylitol, hyaluronic acid, The composition for external use according to claim 1, wherein the composition is one or more selected from the group consisting of polyoxyethylene methyl glucoside. The external composition according to claim 1 or 2, wherein the external composition contains a cationic polymer. The external composition comprising an organic acid in the external composition. In the external composition, the organic acid is selected from the group consisting of malic acid, citric acid, lactic acid, glutamic acid, pyrrolidonecarboxylic acid, formic acid, acetic acid, benzoic acid, benzenesulfonic acid, succinic acid, and benzenesulfonic acid. The composition for external use according to claim 4, wherein the composition is a seed or more. The composition for external use according to any one of claims 1 to 5, which is a composition for external use for scalp and hair. The composition for external use according to claim 6, wherein the composition for scalp and hair is a hair-growth material.