JP2002234836A - Stress-responsive skin care preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a skin care preparation capable of protecting the skin from influences of stress. SOLUTION: This skin care preparation is obtained by including tranexamic acid and a derivative such as an ester or a salt thereof as a stress-responsive agent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a stress remedy and a skin external preparation containing the same, such as a cosmetic.

[0002]

2. Description of the Related Art The present age is a time of stress overload, and more or less living in the present age lives under the influence of the applied stress. In recent years, the effects of such stress on the human body have been investigated in detail, and it has become clear that unexpectedly large effects are expected. It is said that many criminal cases that have a shocking impact on society in recent years are caused by such stress. Such effects are not limited to this. For example, in recent years, the number of people with atopic dermatitis has rapidly increased, or in cosmetics users, hypersensitivity that causes skin troubles when ordinary cosmetics are used. It has been suggested that the background of the rapid increase in the number of people with sensitive skin is the effect of such stresses, as well as the deterioration of the environment. In view of such a situation, there is a demand for the development of a cosmetic that can cope with the rapidly increasing skin roughness of people with atopic dermatitis and sensitive skin. Few substances are known that have the effect of promoting recovery from the adverse effect of stress on the skin or the effect of reducing the effect of stress on the skin. In addition, external preparations for skin promote the recovery from the effects of such stresses and act to prevent the effects of stress on the skin, thereby improving skin roughness such as atopic dermatitis and irritability and preventing skin roughness. No attempt has been made to achieve this.

[0003] On the other hand, tranexamic acid and its derivatives have a whitening effect and an anti-inflammatory effect, and are used as active ingredients in cosmetics for these purposes. No skin external preparation for stress treatment containing this is known at all.

[0004]

The present invention has been made under such circumstances, and an object of the present invention is to provide an external preparation for skin which protects the skin from the effects of stress.

[0005]

In view of such circumstances, the present inventors have sought a skin external preparation that protects the skin from the effects of stress.
As a result of intensive research efforts, we found that tranexamic acid and its derivatives responded to such stress, and further research was conducted to find that the desired skin external preparation could be obtained by incorporating this into skin external preparations. And completed the invention. That is, the present invention relates to the following technology. (1) A stress remedy comprising tranexamic acid and / or a derivative thereof. (2) The stress-treating agent according to (1), wherein the tranexamic acid derivative is a physiologically acceptable salt of tranexamic acid and / or an ester of tranexamic acid. (3) An external skin preparation for treating stress, comprising one or more selected from the stress-treating agents according to (1) or (2). (4) The external preparation for skin according to (3), which is for preventing or improving rough skin caused by stress. (5) An external preparation for stress treatment, comprising one or more selected from tranexamic acid, esters of tranexamic acid and physiologically acceptable salts thereof. (6) The external preparation for skin according to (5), which is for preventing or improving skin roughness due to stress. (7) The external preparation for skin according to any one of claims 3 to 6, which is a cosmetic. Hereinafter, the present invention will be described in more detail focusing on embodiments.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION (1) The agent for treating stress of the present invention The agent for treating stress of the present invention comprises tranexamic acid and / or a derivative thereof. Here, the derivative of tranexamic acid is a bifunctional compound in which tranexamic acid has an amino group and a carboxyl group, so that various derivatives can be easily produced while maintaining physiological effects. A generic term for derivatives that can be easily derived. Examples of such easily derived derivatives include, for example, an alkyl (alkenyl) amine derivative, an alkyl (alkenyl) ester, and an amino group in which a hydrogen atom of an amino group or a carboxyl group is substituted with an alkyl group or an alkenyl group. Examples thereof include amide derivatives in which atoms are substituted with an acyl group, and among these, alkyl (alkenyl) esters that do not modify an amino group are preferred. The carbon chain of such an alkyl (alkenyl) group is preferably from 1 to 30, particularly preferably from 1 to 24. Among these derivatives, esters can be obtained by protecting an amino group with a protecting group such as BOC and then reacting the derivative with an alkyl (alkenyl) chloride in the presence of an alkali, or by reacting an ester with an acyl chloride. Or the ester compound and the carboxylic acid
An N-alkyl (alkenyl) ester can be produced by, for example, reacting with a peptidizing reagent such as CC, and hydrolyzing it under mild conditions to produce an N-alkyl (alkenyl) ester. The derivatives of the present invention also include salts of amino groups or carboxyl groups in addition to such derivatives. The salt is not particularly limited as long as it is physiologically acceptable. For example, for the amino group, mineral salts such as hydrochloride, nitrate, sulfate, phosphate, citrate, and oxalate Salts, organic acid salts such as lactate, carbonates and the like can be preferably exemplified. For the carboxyl group, alkali metal salts such as sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, ammonium Preferred examples include salts, organic amine salts such as triethylamine salt and triethanolamine salt, and basic amino acid salts such as arginine salt and lysine salt. That is, tranexamic acid, a physiologically acceptable salt of tranexamic acid, and / or an ester of tranexamic acid are particularly preferred as the stress response agent of the present invention. Such a stress response agent of the present invention has an effect of preventing stress from affecting skin such as skin roughness, or improving the effect of stress on skin such as skin roughness. Because of this,
It is useful as a stress responding agent for preventing or improving adverse effects such as rough skin due to stress.

(2) A skin external preparation for treating stress according to the present invention is characterized by containing the above-mentioned stress responding agent of the present invention. Such a stress remedy can contain only one kind,
More than one species may be contained in combination. The preferred content of the stress remedy in the skin external preparation for stress of the present invention is 0.001 to 10% by weight, more preferably 0.1 to 10% by weight, based on the total amount of the skin external preparation. 0.01 to 1% by weight. The external preparation for skin of the present invention is characterized in that, by transdermal administration, it has an effect of promoting the recovery of the skin from the adverse effects of stress. Such an effect is, for example, when animals are bred under stress such as overcrowding, and then the skin is damaged by stripping, etc., under stress load,
When the agent for promoting recovery from the adverse effects of the above-mentioned stress is transdermally administered, the recovery of the skin function after stripping is accelerated, that is, the phenomenon of improving the skin function 3 to 4 days after stripping appears. This index value can be obtained from the calculation of the total amount of the dissipated moisture after stripping as shown in Example 1. Here, in the present invention, the skin external preparation is a general term for a substance or a composition which is externally administered to the skin, and specifically, a skin external medicine, a cosmetic, a cleansing agent,
Bath agents, external skin disinfectants, external skin disinfectants and the like can be exemplified. Among these, external skin medicines, cosmetics, cleaning agents, and bath agents are preferred, and cosmetics are particularly preferably applied. The adverse effects of such stress on the skin include, for example, invasion of injury substances, enhancement of various proinflammatory factors and runaway of the immune system, due to a decrease in skin barrier function,
Endocrine system disruption. Since the external preparation for skin of the present invention has an effect of promoting recovery from the effects of stress when stress is applied, it is administered before or during the time when stress is continuously applied. Is particularly preferred. The external preparation for skin of the present invention can contain optional components usually used in external preparations for skin, in addition to the above-mentioned stress remedy which is an essential component. Such components include, for example, hydrocarbons such as squalane, petrolatum, and microcrystalline wax;
Esters such as jojoba oil, carnauba wax, octyldodecyl oleate, triglycerides such as olive oil, tallow, coconut oil, etc., fatty acids such as stearic acid, oleic acid and ritinoleic acid, oleyl alcohol, stearyl alcohol, octyldodecanol and the like Higher alcohols, anionic surfactants such as sulfosuccinates and sodium polyoxyethylene alkyl sulfate, amphoteric surfactants such as alkyl betaine salts, cationic surfactants such as dialkylammonium salts, sorbitan fatty acid esters, fatty acid monoglycerides, These polyoxyethylene adducts, polyoxyethylene alkyl ethers, nonionic surfactants such as polyoxyethylene fatty acid esters, polyethylene glycol, glycerin,
Polyhydric alcohols such as 1,3-butanediol,
Gelling agents, antioxidants, ultraviolet absorbers, coloring agents, preservatives,
It can contain powder and the like. Of these, particularly preferred are polyhydric alcohols. This is because, for example, when the external preparation for skin of the present invention is used during the application of stress, the skin barrier function may be reduced due to the stress previously applied. This is because the polyhydric alcohol can enhance the water retention ability of the skin and complement the skin barrier function. The preferred content of the polyhydric alcohol in the skin external preparation of the present invention is 3 to 15% by weight, more preferably 4 to 10% by weight of the total amount of the polyhydric alcohol relative to the total amount of the cosmetic.
% By weight. In addition, in the skin external preparation of the present invention, a component that relieves inflammation, for example, a nonsteroidal anti-inflammatory drug such as indomethacin or bufexamak, or an anti-inflammatory crude drug such as burdock root extract or birch extract and / or an extract thereof is used. It is also preferable to contain it, because it can suppress the adverse effect of the stress that has already appeared and provide an additive or synergistic effect. The external preparation for skin of the present invention can be produced by treating the above essential components and optional components according to a conventional method.

[0008]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but it is needless to say that the present invention is not limited to such examples.

Example 1 An animal experiment was set up to examine the relationship between overcrowding stress and skin function and the effect of the stress-treating agent of the present invention on it. That is, a 12-week-old Skh
-1 mice (male) were in a normal group with 5 mice (1
The animals were bred at 95.2 cm 2 per animal and the overcrowded stress group was bred at 21 animals per cage (22.7 cm 2 per animal). The breeding period was one week. During this time, the sample administration group applied 0.1 ml of the sample to the back every day. As a specimen, 100 μl of a solution prepared by dissolving the stress-treating agent of the present invention in 50% ethanol was used. The normal group was bred by a normal breeding method during this stress load period. Thereafter, the back was shaved and stripped, and the amount of water dissipated from the skin was measured using a dissipative water meter. Measurements were taken 1, 2, 3 and 4 days after stripping. From these numerical values, the value of Δ (dissipated water amount on the first day in the administration group−dissipated water amount on the nth day in the administration group) was determined as Δ (dissipated water amount on the first day in the control group−nth day on the control group) The value obtained by dividing by the value of the amount of water dissipated in the water was determined as the recovery promotion value (improved value). Table 1 shows the results. The unit of the amount of water dissipated is g
/ M2 / h. From these results, it can be seen that all of the stress-treating agents of the present invention are excellent in the action of promoting the recovery of the living body from the adverse effects of stress (improvement action).

[0010]

[Table 1]

Example 2 An animal experiment was set up to examine the relationship between overcrowding stress and skin function and the effect of the stress-reducing agent of the present invention on it. That is, S of 12 weeks old
kh-1 mice (male) were bred in a normal group with 5 mice per cage (95.2 cm 2 per mouse), and in an overcrowded stress group with 21 mice per cage (22.7 cm per mouse).
Reared in 2). The breeding period was one week. During this time, the sample administration group applied 0.1 ml of the sample to the back every day. The sample used was the same as in Example 1. The normal group was bred by a normal breeding method during this stress load period. Thereafter, the back was shaved and stripped, and the amount of water dissipated from the skin was measured using a dissipative water meter. Measurements were taken on day 0 and day 1 after stripping. Table 1 shows the results.
The unit is g / m2 / h. From the results, the value obtained by subtracting the TEWL on day 0 from the TEWL on day 1 in the administration group from this value in the non-administration group was multiplied by 100, and the value obtained by subtracting TEWL on day 0 in the administration group from the prophylaxis value was 1. The value was calculated as the prevention rate. The results are shown in Table 2. This indicates that the stress response agent of the present invention prevents a decrease in skin barrier function due to stress (preventive effect).

[0012]

[Table 2]

<Example 3> A skin lotion, which is an external preparation for stress treatment according to the present invention, was prepared according to the following formulation. That is, the prescription component was heated and stirred at 80 ° C., and was stirred and cooled to obtain lotion 1. Glycerin 5 parts by weight Sulfated sodium trehalose 0.1 part by weight 1,2-pentanediol 5 parts by weight Ethanol 5 parts by weight Sodium tranexamate 0.001 part by weight Polyoxyethylene (60) hydrogenated castor oil 0.1 parts by weight Water 84 .799 parts by weight

<Example 4> Using the lotion 1 of Example 3, a group of 10 persons with atopic dermatitis was subjected to a use test for 2 weeks. In the use test, it was agreed that the test should be stopped immediately when an unfavorable reaction such as skin trouble occurs. Before and after the test, the amount of dissipated water was measured. The control group used the lotion of Control Example 1 in which the essence of Example 1 was replaced with water. In the control group, three dropouts were observed, and the amount of water loss was 9% on average. However, in the group administered with Example 3, no dropout was 0, and the loss of water loss was on average. 28% was observed, and improvement of atopic dermatitis due to the stress relieving effect of the cosmetic of the present invention, that is, improvement of skin roughness was observed.

Example 5 A cream (cosmetic) was prepared according to the following formulation. That is, the components (a), (b) and (c) are heated to 80 ° C., (b) is gradually added to (a) to emulsify, (c) is neutralized by further adding (c), and the particles are aligned with a homogenizer. Obtained. These showed an excellent effect of improving sensitive skin as in Example 4. Liquid paraffin 10 parts by weight Solid paraffin 5 parts by weight Microcrystalline wax 5 parts by weight Olive oil 20 parts by weight Sorbitan sesquistearate 1.5 parts by weight Glycerin monooleate 1 part by weight Stearic acid 0.3 parts by weight Polyoxyethylene (20) 1.7 parts by weight of behenyl ether 0.1 part by weight of butyl paraben 0.2 part by weight of potassium tranexamate 0.2 part by weight of water 31 parts by weight of carboxyvinyl polymer 0.3 part by weight of propylene glycol 5 parts by weight of methyl paraben 0.2 parts by weight of potassium hydroxide 0.2 parts by weight water 18.5 parts by weight

Example 6 A cream formulation (external medicine for atopic dermatitis) was prepared according to the following formulation. That is, the components (a), (b) and (c) are heated to 80 ° C., (b) is gradually added to (a) to emulsify, (c) is neutralized by further adding (c), and the particles are aligned with a homogenizer. Obtained. All of these had an excellent effect on atopic dermatitis. In particular, the response rate was high in patients who did not respond to the prednisolone preparation. Liquid paraffin 10 parts by weight Solid paraffin 5 parts by weight Microcrystalline wax 5 parts by weight Olive oil 20 parts by weight Sorbitan sesquistearate 1.5 parts by weight Glycerin monooleate 1 part by weight Stearic acid 0.3 parts by weight Polyoxyethylene (20) Behenyl ether 1.7 parts by weight Butyl paraben 0.1 parts by weight Ethyl tranexamate 0.2 parts by weight Prednisolone 1 part by weight Water 30 parts by weight Carboxyvinyl polymer 0.3 parts by weight Propylene glycol 5 parts by weight Methyl paraben 0.2 parts by weight C Potassium hydroxide 0.2 parts by weight Water 18.5 parts by weight

[0017]

According to the present invention, an external preparation for skin that protects the skin from the effects of stress can be provided.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 17/16 A61P 17/16 25/00 25/00 (72) Inventor Katsuo Matsumoto Totsuka-ku, Yokohama-shi, Kanagawa 560 Kashio-cho POLA Kasei Kogyo Co., Ltd. Totsuka Laboratory F-term (reference) 4C083 AA122 AB032 AC012 AC022 AC102 AC122 AC182 AC242 AC422 AC432 AC442 AC482 AC621 AC622 AD092 AD212 AD492 CC04 CC05 DD23 DD27 DD31 EE06 EE12 4C206 AA01 AA02 FA44 MA01 MA04 MA37 MA41 MA83 NA14 ZA02 ZA89

Claims (7)

[Claims] 1. A stress remedy comprising tranexamic acid and / or a derivative thereof. 2. The stress-responsive agent according to claim 1, wherein the tranexamic acid derivative is a physiologically acceptable salt of tranexamic acid and / or an ester of tranexamic acid. 3. A skin external preparation for stress treatment, comprising one or more selected from the stress treatment agents according to claim 1 or 2. 4. The external preparation for skin according to claim 3, wherein the preparation is for preventing or improving skin roughness caused by stress. 5. A tranexamic acid, an ester of tranexamic acid, and a physiologically acceptable salt thereof.
A skin external preparation for stress treatment, comprising at least one kind or two or more kinds. 6. The external preparation for skin according to claim 5, which is used for preventing or improving skin roughness due to stress. 7. The external preparation for skin according to claim 3, which is a cosmetic.