JP2009091341A - Aerosol agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To improve low-temperature and time-dependent stability of adenosine easily depositing under a low temperature in an aerosol formulation. <P>SOLUTION: A raw solution of the aerosol containing the following ingredients (1)-(3) is provided: (1) 1.0-5.0 mass% adenosine based on the base solution, (2) 0-15.0 mass% polyhydric alcohol based on the base solution and (3) 20.0-70.0 mass% lower alcohol based on the base solution. An aerosol product in which a mixture for the aerosol prepared by mixing the base solution and a propellant is enclosed in an aerosol container is also provided. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  This invention is invention related to the aerosol agent used as an external preparation. More specifically, the invention relates to an aerosol agent that improves the stability over time of adenosine, which is likely to precipitate at low temperatures when blended at a certain concentration.

  In the field of external preparations, adenosine is used as a blending component of hair nourishing agent for hair and as a blending component of blood circulation promoter for skin.

  As inventions in the field of external preparations containing adenosine, for example, prior arts shown in the following Patent Documents 1 to 5 are recognized.

However, in particular, when a large amount of adenosine is blended as an aerosol preparation, there is no example in which the stability over time is improved at low temperatures.
JP 2001-288046 A JP 2000-198718 A JP 2004-143184 A JP-A-6-56635 JP-A-5-58845

  The above-described adenosine is known to have an excellent hair nourishing effect and subcutaneous blood circulation promoting effect, and further active utilization is desired. However, adenosine is likely to precipitate at low temperatures, which is an impediment to the development of various products, and it is a very important matter to solve this. The problem to be solved by the present invention is to improve the stability of adenosine over time at low temperatures in an aerosol dosage form.

  As a result of investigations aimed at solving the above problems, the present inventor has found that in the stock solution, polyhydric alcohol is 15.0% by mass or less (including 0% by mass) of the stock solution, and lower alcohol is 20.0% of the stock solution. By adding ~ 70.0 mass%, even if adenosine is blended at about 5.0 mass% of the stock solution, it is practically possible to deposit adenosine at low temperatures in an aerosol dosage form in which high pressure is maintained. The present invention has been completed by finding that it can be suppressed.

That is, the present invention includes the following components (1) to (3):
(1) 1.0-5.0% by mass of adenosine in the stock solution
(2) 0 to 15.0% by mass of polyhydric alcohol in the stock solution
(3) 20.0-70.0% by mass of the lower alcohol in the stock solution
An aerosol product comprising an aerosol stock solution (hereinafter also referred to as the present aerosol stock solution) containing an aerosol, and an aerosol mixture in which the stock solution and the propellant are mixed (hereinafter referred to as the present aerosol mixture) is enclosed in an aerosol container (Hereinafter also referred to as the present aerosol product).

  According to the present invention, there is provided an aerosol agent in which a blended adenosine hardly precipitates even at a low temperature.

[This aerosol stock solution]
The aerosol stock solution is a specific embodiment that is used in the aerosol product in which the aerosol mixture obtained by mixing this with a propellant is enclosed in an aerosol container, and may be a subject of independent transactions. Is.

  Indispensable components of the present aerosol stock solution include adenosine, polyhydric alcohol, and lower alcohol used as a hair nourishing component or a subcutaneous blood circulation promoting component.

(1) adenosine (6-amino -9-beta-D-ribofuranosyl -9 H - purine) is known as one of the ribonucleoside constituting the RNA containing the adenine purine derivatives to the base portion, For example, it can be obtained by hydrolyzing RNA. Commercial products can also be used. As described above, it is known that adenosine has an excellent hair nourishing effect and subcutaneous blood circulation promoting action. “Hair nourishment” as used herein refers to positive effects on hair regeneration, maintenance, and quality improvement, such as hair growth promotion, hair cycle growth, hair thickening, etc. Means.

  The blending amount of adenosine in the present aerosol stock solution is 5.0% by mass or less, preferably 3.0% by mass or less of the stock solution. When adenosine is added in an amount exceeding 5.0% by mass of the stock solution, adenosine precipitation at a low temperature cannot be sufficiently suppressed, and a tendency that stability over time is not sufficiently exhibited is observed. Moreover, the blending of less than 1.0% by mass of the stock solution is stable at a low temperature without applying the present invention, and the necessity of positively applying the present invention is reduced.

(2) Polyhydric alcohol and lower alcohol The polyhydric alcohol and lower alcohol that can be blended in the present aerosol stock solution are appropriately selected and blended as long as they can be blended into an external composition such as cosmetics. Can do.

  Examples of the polyhydric alcohol include glycerol, xylitol, sorbitol, dipropylene glycol, butylene glycol, 1,3-butylene glycol, propylene glycol, polyethylene glycol, polyoxyethylene methyl glucoside, maltitol, mannitol and the like. . Among these, sorbitol and dipropylene glycol can be exemplified as suitable polyhydric alcohols. One or more polyhydric alcohols can be used.

  One or more kinds of lower alcohols can be used, but ethanol is a preferred and practical component.

  The blending amount of the polyhydric alcohol in the aerosol stock solution is in the range of 0 to 15.0% by weight of the stock solution, and the blending amount of the lower alcohol is 20.0 to 70.0% by weight of the stock solution, preferably 30.0%. It is -60.0 mass%. When the ranges of both blending components deviate from these ranges, it tends to be difficult to sufficiently suppress the precipitation of adenosine at low temperatures.

(3) Optional components In addition, the present aerosol stock solution may be blended with various components that can be blended in an external composition such as cosmetics, if necessary, within the range where the effects of the present invention are exhibited. it can.

  The optional ingredient can be selected depending on the specific use of the aerosol product, for example, whether it is a hair nourishing agent or an aerosol product for promoting blood circulation under the skin.

  In the case where the aerosol product is a hair nourishing agent, it is preferable to actively mix known hair nourishing ingredients other than adenosine, anti-leakage agents, cooling agents, and the like. In the case of a product for promoting blood circulation, it is preferable to actively mix other blood circulation promoting components and the like.

  In addition, oils, surfactants, amino acids, organic acids, thickeners, ultraviolet absorbers, water, pH adjusters, chelating agents, pigments, powders, fragrances and the like can be blended as necessary.

(4) Manufacturing Method The aerosol stock solution can be an ethanol / water-based composition or an emulsion composition (particularly an oil-in-water emulsion composition), and is a known manufacture according to the dosage form. The method can be done. In particular, when it is difficult to dissolve adenosine, this problem can be overcome by heating preferably at a limit of 50 ° C. The effect of suppressing the precipitation of adenosine at a low temperature, which is a problem, is exhibited only when the aerosol stock solution is used as the aerosol mixture or the aerosol product.

[Propellant]
A well-known propellant can be used for the propellant used in combination with this aerosol stock solution. Specifically, a liquefied gas such as dimethyl ether (DME) or liquefied petroleum gas (LPG); a compressed gas composed of nitrogen gas, carbon dioxide gas, or the like can be used. In particular, in the present invention, liquefied gas is suitable, and dimethyl ether is particularly preferred because of its good compatibility with the present aerosol stock solution.

  The mixing ratio of the propellant in the aerosol mixture, in other words, the ratio of the propellant to the total mass of the aerosol stock solution and the propellant in the aerosol container is 20.0 to 70.70 as dimethyl ether with respect to the entire mixture. 0% by mass, preferably 30.0-60.0% by mass. Moreover, it is preferable that 50.0-100 mass% of dimethyl ether coexists in the said propellant.

[Aerosol products]
This aerosol product is obtained by enclosing the above-mentioned aerosol stock solution and propellant in an aerosol container in the state of a mixture for this aerosol.

  Since the aerosol mixture is sealed in the aerosol container in a pressurized state, the aerosol container needs to be a pressure resistant container. If the pressure resistance specified by the regulations (not deformed at 1.3 Ma and not broken at 1.5 Ma) is maintained, the material of the pressure vessel can be any of aluminum, glass, tinplate, and synthetic resin. Also good. Further, the aerosol container is provided with a valve, a button, a spout, a cap and the like in addition to the pressure resistant container, similarly to a known aerosol container. Moreover, the method for enclosing the aerosol mixture in the aerosol container can also be performed in accordance with a known method such as cooling filling, undercap type pressure filling, and through-the-valve type pressure filling. The initial internal pressure of the aerosol mixture thus encapsulated in the aerosol container is 0.05 to 0.70 MPa (25 ° C. unless otherwise specified), preferably 0.10 to 0 .60 MPa. If the internal pressure exceeds 0.70 MPa, there is a risk of rupture and the like, and if it is less than 0.05 MPa, adenosine deposition tends to cause a problem in practical use.

  As described above, the aerosol product in which the aerosol mixture composed of the aerosol stock solution and the propellant is enclosed is configured.

  This aerosol product can be applied to all uses brought about by the action of adenosine by external application. For example, it can be used as an aerosol product for hair restoration, an aerosol product for promoting skin blood circulation, an aerosol product for preventing dullness using the skin blood circulation promoting effect, an aerosol product for preventing skin aging, etc. Absent.

  Hereinafter, examples of the present invention will be disclosed to more specifically disclose the present invention. The blending amount in the column of this example is mass%, and adenosine is displayed as the solid content. Further, the MPa indicating the pressure is a value at 25 ° C. unless otherwise specified, as described above. In addition, what is displayed as a comparative example below indicates a relative status in the same test system, and only the fact that it is displayed as “comparative example” is out of the scope of the present invention. It does not indicate that.

[Examples 1-15, Comparative Examples 1-11]
Comparative examples in which the formulation shown in Tables 1 to 5 was used to prepare a stock solution for aerosol (scalp scalp hair lotion) according to the following production method, and these scalp scalp hair lotions were directly put into vials by the following test. And the low temperature stability at 0 degreeC in the Example filled with the said lotion with the propellant so that it might become the internal pressure of 0.08-0.57 MPa with the glass pressure bottle was examined. The test results are also shown in Tables 1 to 5.

〔Production method〕
Polyhydric alcohol (sorbitol dipropylene glycol) 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. When adenosine was difficult to dissolve, the solution was heated to 50 ° C. or lower and stirred to dissolve adenosine.

[Test methods and evaluation criteria]
A test product in which adenosine was completely dissolved in this manner was sealed in a vial with a lid as it was and a sample sealed in a glass pressure-resistant bottle together with a propellant was allowed to stand at 0 ° C. for 1 month, and after 1 month. The precipitation of adenosine crystals was visually examined. As in the beginning of the test, the case where adenosine was dissolved without any change was evaluated as “◯”, and the case where a slight amount of adenosine crystal was precipitated was evaluated as “Δ”. Those that could be discriminated were evaluated as “×”.

  From the results shown in Table 1, in Examples 3 and 4 in which DME was encapsulated as a propellant, precipitation was suppressed even at a low temperature even in a state where 2.5% by mass or more of adenosine was contained. It can be seen that the stability of the preparation is improved. On the other hand, in Comparative Examples 3 and 4 which are lotions containing 2.5% by mass or more of adenosine, it was revealed that precipitation of adenosine at low temperatures was remarkably observed. In Comparative Examples 1 and 2 having a small amount of adenosine, precipitation of adenosine at low temperatures was essentially not observed as in Examples 1 and 2.

  In Table 2, in Comparative Example 6 in which 80.0% by mass of ethanol which is a lower alcohol was blended, 2.5% by mass of adenosine could not be dissolved. In Comparative Example 5 of ethanol 10.0%, DME was not dissolved. Even when encapsulated as a propellant, adenosine precipitated slightly. As can be seen in Examples 5 to 8, when the blending amount of ethanol is 20.0 to 70.0% by mass, the suppression of adenosine precipitation at low temperatures when DME is encapsulated as a propellant is remarkable. It became clear that there was.

  In Table 3, in Comparative Example 7 in which 20.0% by mass of dipropylene glycol, which is a polyhydric alcohol, was not able to dissolve 2.5% of adenosine, as can be seen in Examples 9-13, Clearly, if the amount of polyhydric alcohol is 15.0% by mass or less (including 0% by mass), the suppression of adenosine precipitation at low temperatures when DME is encapsulated as a propellant is obvious. became.

  In Table 4, when 50.0 mass% or more of LPG was mixed with the propellant, it was found that adenosine precipitates at a low temperature as observed in Comparative Examples 9 and 10. As shown in Examples 14 to 16, if DME accounts for 50.0% by mass or more of the propellant, as shown in Comparative Example 8, the formulation of 3.0% by mass of adenosine precipitated in the vial is also included. It was found that the precipitation of adenosine at low temperatures was significantly suppressed.

  In Table 5, as can be seen in Examples 17 to 20 and Comparative Examples 11 to 13, even in the case of 3.0% by mass of adenosine precipitated at a low temperature, the propellant was DME as a whole. It was revealed that the suppression of adenosine precipitation at a low temperature is remarkable when it accounts for 0.0 to 70.0% by mass.

  Hereinafter, other examples of the aerosol product will be disclosed. The low temperature stability of these examples was evaluated as “◯” in the low temperature stability test.

[Example 15] Lotion for scalp
Compounding component amount (% by mass)
(Stock solution)
95% ethanol 60.0
Dipropylene glycol 5.0
Adenosine 3.0
l-Menthol 0.5
Polyoxyethylene hydrogenated castor oil 0.5
Isostearyl alcohol 0.5
Purified water Residual fragrance Appropriate amount Malic acid Appropriate amount (propellant)
DME 20.0
LPG (0.43 MPa at 20 ° C.) 20.0
Stock solution 60.0
<Manufacturing method>
Add humectant, menthol, fragrance, isostearyl alcohol to ethanol, add activator, acid, and adenosine to water. The obtained lotion is filled in an aerosol can, and DME and LPG are encapsulated as a propellant to produce a lotion for the scalp as an aerosol product.

[Example 16] External preparation for skin
Compounding component amount (% by mass)
(Stock solution)
95% ethanol 20.0
Squalane 1.0
Butylene glycol 5.0
Polyoxyethylene hydrogenated castor oil 0.2
Glycerin 5.0
Adenosine 0.2
Purified water residue (propellant)
DME 50.0
Stock solution 50.0
<Manufacturing method>
Add oil and activator to some water and emulsify, dissolve other components in water, and stir and mix them. The obtained skin external preparation is filled into an aerosol can, and DME is sealed as a propellant to produce the skin external preparation as an aerosol product.

[Example 17] Hair restorer
Compounding component amount (% by mass)
(Stock solution)
95% ethanol 30.0
Butylene glycol 5.0
Adenosine 5.0
l-Menthol 0.5
β-glycyrrhetinic acid 0.1
Pantothenyl ethyl ether 0.3
Dipotassium glycyrrhizinate 0.2
Decyltetradecyldimethylamine oxide solution (20%) 3.0
dl-α-tocopherol
2-L-ascorbic acid diester potassium salt 0.2
Polyoxyethylene hydrogenated castor oil 0.5
Purified water Residual fragrance Appropriate amount of lactic acid Appropriate amount of sodium lactate Appropriate amount (propellant)
DME 30.0
LPG (0.43 MPa at 20 ° C.) 20.0
Stock solution 50.0
<Manufacturing method>
Add a moisturizer, oil, and fragrance to ethanol, add an activator, a pH adjuster, a drug, and adenosine to water. The obtained undiluted solution is filled into an aerosol can, and DME and LPG are encapsulated as a propellant to produce a lotion for scalp as an aerosol product.

[Example 18] Tonic for scalp
Compounding component amount (% by mass)
(Stock solution)
95% ethanol 70.0
Propylene glycol 8.0
Adenosine 2.0
l-Menthol 0.1
Salamander extract 3,0
Pepper tincture 0.2
Amateur extract 0.5
Purified water Residual perfume Appropriate amount Lactic acid Appropriate amount Sodium lactate Appropriate amount (propellant)
DME 20.0
Stock solution 80.0
<Manufacturing method>
Add a moisturizer, oil, and flavor to ethanol, add an activator, pH adjuster, drug, and adenosine to water. The obtained stock solution is filled into an aerosol can, and DME and LPG are encapsulated as a propellant to produce a lotion for the scalp as an aerosol product.

[Example 19] External preparation for skin
Compounding component amount (% by mass)
(Stock solution)
95% ethanol 30.0
Volatile isoparaffin 1.2
Sorbitol 7.0
Glycerin 5.0
Daylily extract BG 0.2
Fennel extract BG 1.0
Monoammonium glycyrrhizinate 0.3
Dl-α-tocopherol acetate 0.2
Nicotinic acid dl-α-tocopherol 0.5
Nicotinamide 0.1
Adenosine 2.5
Purified water residue (propellant)
DME 50.0
Stock solution 50.0
<Manufacturing method>
Oil and activator are added to some water to emulsify, other components are dissolved in water, and both are stirred and mixed. The obtained skin external preparation is filled into an aerosol can, and DME is sealed as a propellant to produce the skin external preparation as an aerosol product.

[Example 20] External preparation for skin
Compounding component amount (% by mass)
(Stock solution)
95% ethanol 22.0
Decamethylcyclopentasiloxane 3.2
Sorbitol 2.0
Dipropylene glycol 5.0
Benzyl nicotinate 0.1
Hinokitiol 0.3
Lavender oil 1.2
Polyoxyethylene hydrogenated castor oil 1.0
O- [2-hydroxy-3- (trimethylammonio) propyl] chloride
Hydroxyethyl cellulose 0.1
Adenosine 2.5
Purified water residue (propellant)
DME 30.0
LPG (0.43 MPa at 20 ° C.) 5.0
Stock solution 65.0
<Manufacturing method>
Oil and activator are added to some water to emulsify, other components are dissolved in water, and both are stirred and mixed. The obtained skin external preparation is filled into an aerosol can, and DME is sealed as a propellant to produce the skin external preparation as an aerosol product.

Claims (5)

An aerosol stock solution containing the following components (1) to (3).
(1) 1.0-5.0% by mass of adenosine in the stock solution
(2) 0 to 15.0% by mass of polyhydric alcohol in the stock solution
(3) 20.0-70.0% by mass of the lower alcohol in the stock solution An aerosol mixture comprising the aerosol stock solution according to claim 1 and a propellant. The aerosol mixture according to claim 2, wherein the aerosol mixture contains 50.0 to 100% by mass of dimethyl ether in the propellant. An aerosol product, wherein the aerosol mixture according to claim 2 or 3 is enclosed in an aerosol container. The aerosol product according to claim 4, wherein the aerosol product is a hair nourishing agent.