JP2006008550A - Antiaging agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a novel antiaging agent, in detail, an external preparation for the skin effective for inhibiting the formation of wrinkles by drying and/or ameliorating the formed wrinkles. <P>SOLUTION: The antiaging agent comprises a prourokinase activation inhibitor and/or a urokinase inhibitor, particularly one or more kinds selected from an amide derivative of tranexamic acid represented by formula (1) [wherein R<SB>1</SB>and R<SB>2</SB>are each independently hydrogen, a 1-18C linear or branched alkyl group, a 5-8C cycloalkyl group, a benzyl group or formula (2) (wherein X is a lower alkyl group, a lower alkoxy group, a hydroxy group, an amino group or a halogen; and n is 0-3)] and its cosmetically acceptable salt. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention provides an anti-aging agent containing a pro-urokinase activation inhibitor and / or a urokinase inhibitor as an active ingredient. In particular, the present invention relates to an anti-aging agent comprising, as an active ingredient, an amide derivative of tranexamic acid, which is a prourokinase activation inhibitor, or a cosmetically acceptable salt thereof, specifically, suppressing wrinkle formation due to drying and / or Provided is an external preparation for skin that is effective in improving formed wrinkles.

  In the field of cosmetics and dermatology, various means have been proposed and attempted to improve or treat the influence of the external environment such as dry atmosphere and sunlight irradiation on the skin and damage due to aging. For example, changes in skin due to drying mainly include formation of wrinkles, hardening or a decrease in elasticity.

  As a cause of such changes, the main interest is directed to the functional deterioration of collagen fibers and elastic fibers composed of collagen, elastin, and glucosaminoglycan in the skin dermis. Until now, as means for preventing or repairing such changes, the use of hydroxycarboxylic acids to suppress keratin and wrinkles by preventing collagen fiber loss (eg, Japanese Patent No. 253339), glucos in human fibroblasts, The use of a lysophospholipid that exhibits a moisturizing effect in the dermis by enhancing the ability to produce saminoglycan (specifically hyaluronic acid) has been studied (Japanese Patent Laid-Open No. 8-67621).

  On the other hand, as a result of research on skin roughness caused by dryness and washing, etc., from a viewpoint different from conventional cosmetic research, it has been clarified that proteases play an important role in the occurrence of skin roughness. Yes. For example, it is thought that proteases in epidermal cells play an important role in the normal keratinization process of skin, but in skin where epidermal cells have abnormally proliferated by stimulation such as drying and cleaning agents, It has been clarified that plasminogen localized in the vicinity of the basal epidermis is scattered as active plasmin in the entire epidermis (Kitamura et al .: Cosmetic Technology Journal; 29 (2), 133 (1995) (Non-Patent Document 1)). Plasmin is a protease in which its precursor plasminogen is activated by plasminogen activator (PA), and plays an important role in inhibiting blood clot formation in the blood coagulation system. Nonspecific proteolytic action destroys tissues and cells, produces harmful peptides that can cause inflammation and anaphylactic shock, such as dilation of capillaries, increased vascular permeability, smooth muscle contraction, and pain. It is known to have an adverse effect on people.

  In addition, once the skin barrier function is destroyed, the activity of urokinase, one of PAs, increases in the upper layer of skin before abnormal growth of epidermal cells and changes in skin appearance occur. Yes. Since urokinase has an action of promoting cell proliferation, excessive increase is considered to be one of the causes of epidermal thickening. Urokinase is produced by cleavage and activation of its inactive precursor, prourokinase. Therefore, by suppressing the activation of prourokinase leading to urokinase, it is possible to improve and prevent abnormal growth of the epidermis such as rough skin and acne caused by stimulation such as drying and cleaning agents (Japanese Patent Laid-Open No. 2003-2821). (Patent Document 3)).

As described above, some studies have been conducted on the role and involvement of proteases in rough skin caused by drying and washing, and the countermeasures for them, but the role of various proteases in the aging phenomenon due to drying, especially wrinkle formation.・ Involvement has not been fully elucidated.
JP-A-6-72843 JP 2002-212068 A JP2003-2821 Cosmetic Technology Journal; 29 (2), 133 (1995)

  An object of the present invention is to provide an anti-aging agent, particularly an external preparation for skin which is effective for suppressing wrinkle formation due to drying and / or improving wrinkles formed at a new end completely different from the prior art.

  The present inventor examined the relationship between dry skin and urokinase (plasminogen activator) activity, which has low stratum corneum water content and is likely to wrinkle, and found that urokinase activity was significantly enhanced in dry skin. I found out. A drug that inhibits activation of prourokinase leading to urokinase (hereinafter sometimes simply referred to as “prourokinase activation inhibitor”) is applied to such dry skin, and wrinkle formation is suppressed by suppressing urokinase activity. The present inventors have found that it can be significantly improved / prevented and have completed the present invention.

（式中、Ｒ₁及びＲ₂は水素原子、炭素数１〜１８の直鎖状または分岐状アルキル基、炭素数５〜８のシクロアルキル基、ベンジル基または下記一般式（２）を示し、Ｒ₁及びＲ₂はそれぞれ同一でも異なってもよい。

[式中、Ｘは低級アルキル基、低級アルコキシ基、ヒドロキシ基、アミノ基、またはハロゲン原子を示し、n＝０〜３である。]）。
[４] 前記ウロキナーゼ阻害剤がアミロライド、酸化亜鉛及び酸化亜鉛と他の無機または有機化合物との複合体からなる群より選択される１種または２種以上であることを特徴とする、[１]〜[３]のいずれかの抗老化剤。 Accordingly, the present invention provides the following inventions.
[1] An anti-aging agent for preventing wrinkle formation by drying and / or improving wrinkles formed, comprising a prourokinase activation inhibitor and / or a urokinase inhibitor as an active ingredient.
[2] An anti-aging agent for preventing wrinkle formation by drying and / or improving wrinkles formed, comprising a prourokinase activation inhibitor as an active ingredient.
[3] The prourokinase activation inhibitor is one or more selected from the group consisting of amides of tranexamic acid represented by the following general formula (1) and cosmetically acceptable salts thereof: The anti-aging agent according to [1] or [2], characterized in that:

(Wherein R ₁ and R ₂ represent a hydrogen atom, a linear or branched alkyl group having 1 to 18 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms, a benzyl group, or the following general formula (2); R ₁ and R ₂ may be the same or different.

[Wherein, X represents a lower alkyl group, a lower alkoxy group, a hydroxy group, an amino group, or a halogen atom, and n = 0 to 3. ]).
[4] The urokinase inhibitor is one or more selected from the group consisting of amiloride, zinc oxide and a complex of zinc oxide and other inorganic or organic compounds, [1] Anti-aging agent in any one of-[3].

（式中、Ｒ₁及びＲ₂は水素原子、炭素数１〜１８の直鎖状または分岐状アルキル基、炭素数５〜８のシクロアルキル基、ベンジル基または下記一般式（２）を示し、Ｒ₁及びＲ₂はそれぞれ同一でも異なってもよい。

［式中、Ｘは低級アルキル基、低級アルコキシ基、ヒドロキシ基、アミノ基、またはハロゲン原子を示し、n＝０〜３である。］）。
[８] 前記ウロキナーゼ阻害剤がアミロライド、酸化亜鉛及び酸化亜鉛と他の無機または有機化合物との複合体からなる群より選択される１種または２種以上であることを特徴とする、[５]〜[７]のいずれかの方法。 [5] A method for preventing wrinkle formation and / or improving wrinkles formed by drying, characterized by inhibiting the activation of prourokinase and / or inhibiting the activity of urokinase. Such methods include treatment methods, prevention methods, beauty methods, makeup methods, and the like.
[6] A method for preventing wrinkle formation by drying and / or improving wrinkles formed, which comprises inhibiting activation of prourokinase.
[7] One or two types of inhibition of the activation of prourokinase selected from the group consisting of amides of tranexamic acid represented by the following general formula (1) and cosmetically acceptable salts thereof Method [5] or [6] achieved by applying the above to the skin:

(Wherein R ₁ and R ₂ represent a hydrogen atom, a linear or branched alkyl group having 1 to 18 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms, a benzyl group, or the following general formula (2); R ₁ and R ₂ may be the same or different.

[Wherein, X represents a lower alkyl group, a lower alkoxy group, a hydroxy group, an amino group, or a halogen atom, and n = 0 to 3. ]).
[8] The urokinase inhibitor is one or more selected from the group consisting of amiloride, zinc oxide and a complex of zinc oxide and other inorganic or organic compounds, [5] One of the methods of [7].

  INDUSTRIAL APPLICABILITY According to the present invention, an anti-aging agent, particularly a skin external preparation effective for suppressing wrinkle formation due to drying and / or improving wrinkles formed is provided.

  Urokinase is a serine protease that is one of thrombolytic enzymes and has a function of converting plasminogen, which is a precursor enzyme of fibrinolytic enzyme, into active plasmin. In vivo, urokinase expresses its activity by cleavage and activation of its inactive precursor prourokinase. As described above, it has been found that the activity of urokinase is enhanced in skin with dry skin (JP 2003-22821), but regarding the relationship with the skin aging due to dryness, especially wrinkle formation, No one has been elucidated. The term “aging” as used in the present invention refers to skin changes accompanying aging, and more specifically, beauty such as “increase in wrinkles of skin”, “sagging of skin”, “decrease in skin elasticity”, etc. It refers to various undesirable changes. In addition, “wrinkle” is a change in the form of the skin that appears clearly as a muscular pattern compared to the texture composed of the skin mound and skin groove, and is one of the most prominent changes in which appearance of skin aging appears in the appearance. It appears on the face, neck, and other parts of the body, increases, and when it gets deeper, it appears to be aged. These are essentially distinguished from the morphological point of being accompanied by rough skin, acne scalp and the like accompanied by partial peeling on the stratum corneum due to drying and the like, and partial disappearance of the skin groove.

  The term “wrinkle prevention” as used in the present invention means that the anti-aging agent according to the present invention is applied to the skin in advance to prevent the formation of wrinkles on the skin exposed to an environment where wrinkles are easily formed, such as a dry environment. It means to do. In the present invention, “improving formed wrinkles” means significantly reducing the length, depth, number, etc., of wrinkles formed on the skin by exposure to an environment in which wrinkles are easily formed. That means. The presence / absence of such “wrinkle prevention” and “improvement of formed wrinkles” can be determined quantitatively or qualitatively, and in order to improve accuracy, for example, a double shielding pair comparison method (ICH guideline) It is possible to determine by E9).

  The amide form of tranexamic acid, which is a prourokinase activation inhibitor according to the present invention, and cosmetically acceptable salts thereof include, for example, ActaPharm. Suecica, 7, 441 (1970); J. Med. Chem., 15 , 247 (1972) and the like.

  For example, after protecting the amino group of tranexamic acid with an appropriate protecting group, such as a benzyloxycarbonyl group, the protected component or a reactive derivative of the protected body is reacted with an amine component, thereby An amide body is produced. As the reactive derivative of the protector, acid halides such as acid chloride and acid bromide, mixed acid anhydrides and the like are suitable. Thereafter, the protecting group is removed by catalytic reduction or the like to produce an amide of tranexamic acid.

  The tranexamic acid amide is a cosmetically acceptable salt, if desired, for example, an inorganic acid salt such as hydrochloric acid, sulfuric acid, phosphoric acid, hydrobromic acid, or acetic acid, lactic acid, maleic acid, fumaric acid, tartaric acid, Organic acid salts such as citric acid, methanesulfonic acid and p-toluenesulfonic acid can be used.

  Specific examples of substance names include trans-4-aminomethylcyclohexanecarbonamide, trans-4-aminomethylcyclohexanecarbonamide hydrochloride, Nn-hexyl-trans-4-aminomethylcyclohexanecarbonamide, hydrochloric acid N- n-hexyl-trans-4-aminomethylcyclohexanecarbonamide, Nn-heptyl-trans-4-aminomethylcyclohexanecarbonamide, Nn-heptyl-trans-4-aminomethylcyclohexanecarbonamide hydrochloride, Nn -Butyl-trans-4-aminomethylcyclohexanecarbonamide, hydrochloric acid Nn-butyl-trans-4-aminomethylcyclohexanecarbonamide, Nn-propyl-trans-4-aminomethylcyclohexanecarbonamide N-cyclohexyl-trans-4-aminomethylcyclohexanecarbonamide, hydrochloric acid N-cyclohexyl-trans-4-aminomethylcyclohexanecarbonamide, N, N-dicyclohexyl-trans-4-aminomethylcyclohexanecarbonamide, hydrochloric acid N, N -Dicyclohexyl-trans-4-aminomethylcyclohexanecarbonamide, N, N-diethyl-trans-4-aminomethylcyclohexanecarbonamide, N, N-diethyl-trans-4-aminomethylcyclohexanecarbonamide hydrochloride, N-benzyl- Trans-4-aminomethylcyclohexanecarbonamide, N-benzyl-trans-4-aminomethylcyclohexanecarbonamide hydrochloride, N- (4'-methoxyphenyl) -trans- -Aminomethylcyclohexanecarbonamide, hydrochloric acid N- (4'-methoxyphenyl) -trans-4-aminomethylcyclohexanecarbonamide, N- (4'-ethoxyphenyl) -trans-4-aminomethylcyclohexanecarbonamide, hydrochloric acid N -(4'-Ethoxyphenyl) -trans-4-aminomethylcyclohexanecarbonamide, N- (2'-methylphenyl) -trans-4-aminomethylcyclohexanecarbonamide, hydrochloric acid N- (2'-methylphenyl)- Trans-4-aminomethylcyclohexanecarbonamide, N- (3'-methylphenyl) -trans-4-aminomethylcyclohexanecarbonamide, hydrochloric acid N- (3'-methylphenyl) -trans-4-aminomethylcyclohexanecarbonamide N- (4′-chlorophenyl) -trans-4-aminomethylcyclohexanecarbonamide, hydrochloric acid N- (4′-chlorophenyl) -trans-4-aminomethylcyclohexanecarbonamide, and the like.

  Examples of the urokinase inhibitor according to the present invention include amiloride, zinc oxide, and a complex of zinc oxide and other inorganic or organic compounds.

  The total amount of the pro-urokinase activation inhibitor and / or urokinase inhibitor is preferably 0.001 to 30% by mass, particularly 0.01 to 15% by mass, based on the total amount of the anti-aging agent. If it is less than 0.001% by mass, the anti-aging effect of the present invention is not sufficiently exhibited, and if it exceeds 30% by mass, it is not preferable in terms of usability. The ratio of the activity of prourokinase activation inhibitor: urokinase inhibitor is not particularly limited, but is preferably 1 to 3: 5 to 8.

  The dosage form of the anti-aging agent of the present invention is arbitrary, and any dosage form such as solution system, solubilization system, emulsification system, powder dispersion system, water-oil two-layer system, water-oil-powder three-layer system, etc. It doesn't matter. In addition, the use of the anti-aging agent of the present invention is optional, such as facial cosmetics such as lotions, emulsions, creams, gels, packs, makeup cosmetics such as foundations, lipsticks, eye shadows, body cosmetics, aromatic cosmetics, It can be used for cleaning agents, ointments, bath preparations and the like. The anti-aging agent of the present invention is particularly preferably applied to the outer skin. The application method is not particularly limited, but for example, it is preferably applied to the epidermis at least once a day, for example, 1 to 3 times a day, depending on the area of the skin to be applied, for example 1 to 5 ml.

  In addition to the above essential components, components commonly used in external preparations for skin such as cosmetics and pharmaceuticals, for example, moisturizers, antioxidants, oily components, ultraviolet absorbers, emulsifiers, surfactants, thickeners, alcohols , Powder components, coloring materials, aqueous components, water, various skin nutrients, and the like can be appropriately blended as necessary.

  Others, disodium edetate, trisodium edetate, sodium citrate, sodium polyphosphate, sodium metaphosphate, sequestering agents such as gluconic acid, caffeine, tannin, verapamil, tranexamic acid and its derivatives, licorice extract, grabrizine , Hot water extract of fire thorn fruit, various herbal medicines, drugs such as tocopherol acetate, glycyrrhizic acid and its derivatives or salts thereof, whitening agents such as vitamin C, magnesium ascorbate phosphate, glucoside ascorbate, arbutin, kojic acid , Sugars such as glucose, fructose, mannose, sucrose, trehalose and the like can be appropriately blended.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further more concretely, the technical scope of this invention should not be limitedly interpreted by this Example. In addition, in the following examples etc., the numerical value showing a compounding quantity is represented by the mass% with respect to the whole object mix | blended unless there is particular notice.

結果の示すとおり、ウロキナーゼ活性を有する角層水分量は、ウロキナーゼ活性を有しない角層水分量と比べ、統計学上有意に低かった。従って、角層水分量が多く、いわゆる潤いのあるとされる肌に比べ、角層水分量の低い、いわゆるしわの形成しやすい乾燥肌においては、ウロキナーゼの活性が有意に亢進していることが明らかとなった。 Test 1) Relationship between dry skin and urokinase activity The urokinase activity on the stratum corneum was measured in 42 females whose skin tends to dry out in winter. Specifically, a cellophane tape was lightly pressed on the cheek, which was the test site of the subject, whose stratum corneum moisture content was previously measured with SKINCON-200 (IBI S Co., Ltd.), and the outer stratum corneum layer was peeled off. The collected stratum corneum was allowed to stand on a fibrin plate containing plasminogen and left at 37 ° C. for 180 hours. The presence of urokinase activity was confirmed by lysis of the fibrin plate. The following table shows the results of data for 42 people.

As the results show, the stratum corneum water content with urokinase activity was statistically significantly lower than the stratum corneum water content without urokinase activity. Therefore, urokinase activity is significantly enhanced in dry skin with a high stratum corneum moisture content and so-called moisturized skin, which has a low stratum corneum moisture content and is easily wrinkled. It became clear.

この配合化粧水を用い、顔面頬部の肌荒れが左右同程度の成人男女モニター40名（男性28名、女性12名）について、二重遮蔽対比較法により、トラネキサム酸メチルアミド塩酸塩のしわ防止効果を評価した。 Test 2) Evaluation of fine wrinkles based on skin surface condition (replica) after continuous use for 4 weeks of test sample Formulation cosmetics with and without the following formulation containing 0.7% tranexamic acid methylamide hydrochloride, a prourokinase activation inhibitor Water (A) and (P) were each prepared.

Using 40% of adult male and female monitors (28 males, 12 females) with rough skin on the face and cheeks using this skin lotion, the effect of tranexamic acid methylamide hydrochloride on wrinkle prevention is achieved by the double shielding pair comparison method. Evaluated.

  Specifically, after washing the face twice a day, each subject himself / herself applied an appropriate amount of a sample labeled “for right” on the right face and a sample labeled “for left” on the left face. Note that it is recorded for each subject whether the “right” or “left” sample is the formulated lotion (A) or (P). Application of the test sample was instructed to be performed with the right palm for “right” and with the left palm for “left” to avoid mixing of both test samples.

The test start date and 4 weeks later are the observation measurement days, and a black dot (mark of the observation site) is marked with a liquid liner at 3 cm below the right and left eye corners, and a silicone rubber replica agent (Shiseido) is centered on that point. A skin surface replica of the left and right cheeks of the face was collected using Lot No. 220161). The collected replica was observed with a stereomicroscope (Olympus) at a magnification of 10 times centering on the black dots (marks of the observation site). Based on the criteria shown in the table below, The degree of skin surface condition in the cheeks was evaluated and given a score. The difference between the scores after 4 weeks and the test start date was taken as the improvement.

表中、
「Ａ＞Ｐ」は配合化粧水Ａの塗布による改善度が、配合化粧水Ｐの塗布による改善度を上回った場合；
「Ａ＝Ｐ」は改善度が同等の場合；
「Ａ＜Ｐ」は配合化粧水Ａの塗布による改善度が、配合化粧水Ｐの塗布による改善度を下回った場合；
である。 The following table shows the results for 40 people.

In the table,
“A> P” indicates that the improvement by the application of formulated lotion A exceeds the improvement by the application of formulated lotion P;
“A = P” means the improvement is equivalent;
When “A <P” is less than the improvement due to the application of the formula lotion P, the improvement due to the application of the formula lotion P;
It is.

  As shown in the results, the continuous use of the lotion formulated with 0.7% tranexamic acid methylamide hydrochloride (formulation (A)) compared to the lotion not formulated with tranexamic acid methylamide hydrochloride (formulation (B)). Statistically significant inhibition of wrinkle formation. Therefore, it was revealed that wrinkle formation caused by drying or the like can be suppressed by suppressing urokinase activity on the stratum corneum.

Formulation Example 1: Lotion A formulation example of a lotion containing an active ingredient exhibiting an anti-aging effect according to the present invention is shown.
No. Name Formulation 1 Glycerin 1
2 Dipropylene glycol 12
3 Citric acid 0.02
4 Methylparaben 0.1
5 Ethanol (95%) 8
6 POE methyl glucoside 3
7 POE (24) POP (13) decyl tetradecyl ether 0.4
8 Sodium citrate 0.08
9 Hydroxypropyl-β-cyclodextrin 0.5
10 Thiotaurine 0.01
11 Adenosine triphosphate-2sodium 0.01
12 Sodium hyaluronate 0.01
13 EDTA-3Na 0.01
14 Sodium hydroxymethoxybenzophenone sulfonate 0.05
15 Hydroxyethyl cellulose 0.15
16 Phytosterol 0.1
17 Ibuki-mako extract 0.5
18 Beech bud extract 0.2
19 Asenyaku Extract 2
20 Clara extract 1
21 Tranexamic acid ethylamide hydrochloride 0.6
22 Purified water Residual 23 Perfume appropriate amount 24 Colorant appropriate amount

Formulation Example 2: Emulsion 1
The formulation example of the emulsion which mix | blended the active ingredient which exhibits the anti-aging effect based on this invention is shown.
No. Name Compounding amount 1 Methylpolysiloxane 2
2 Decamethylcyclopentasiloxane 2
3 Safety Hensei alcohol 5
4 Glycerin 6
5 1,3-butylene glycol 5
6 Polyoxyethylene methyl glucoside 3
7 Sunflower 0.1
8 Squalane 0.5
9 Potassium hydroxide 0.1
10 Sodium metaphosphate 0.05
11 Paraoxybenzoic acid ester 0.2
12 Sodium hydroxymethoxybenzophenone sulfonate 0.05
13 Peonies extract 1
14 Yukinoshita extract 0.5
15 Yokuinin Extract 2
16 Peppermint extract 0.1
17 Melissa extract 0.5
18 Xanthan gum 0.05
19 Carboxyvinyl polymer 0.15
20 Acrylic acid / alkyl methacrylate copolymer 0.1
21 Tranexamic acid propylamide lactate 1.2
22 Oxide subsalt 5.0
23 Purified water Residual 24 Perfume appropriate amount 25 Coloring material appropriate amount

Formulation Example 3: Emulsion 2
Another prescription example of the emulsion containing the active ingredient exhibiting the anti-aging effect according to the present invention will be shown.
No. Name Compounding amount 1 Methylpolysiloxane 1
2 Behenyl alcohol 1
3 Batyl alcohol 0.5
4 Nouglycerin 10
5 1,3-butylene glycol 7
6 Erythritol 1.5
7 Kouyuyu 5
8 Squalane 8
9 Tetra-2-ethylhexanoic acid pentaerythrit 2
10 Polyoxyethylene glyceryl isostearate 1.5
11 Polyoxyethylene glycerol monostearate 1
12 Potassium hydroxide 0.1
13 Sodium metaphosphate 0.1
14 Phenoxyethanol 0.5
15 Carboxyvinyl polymer 0.15
16 Ages extract 0.5
17 Achillea millefolium extract 0.1
18 Hamamelis extract 0.5
19 Hinogi extract 1
20 Lavender extract 2
21 Tranexamic acid hexylamide citrate 1.5
22 Silica-coated oxide suboxide 5.0
23 Purified water Residual 24 Perfume appropriate amount 25 Coloring material appropriate amount

Formulation Example 4: Cream 1
The formulation example of the cream which mix | blended the active ingredient which exhibits the anti-aging effect based on this invention is shown.
No. Name Compounding amount 1 Liquid paraffin 5.00
2 Petrolatum 1.00
3 Methylpolysiloxane 1.00
4 Stearyl alcohol 2.00
5 Behenyl alcohol 2.00
6 Nouglycerin 8.00
7 Dipropylene glycol 5.00
8 Macadamia Nutyu 0.50
9 Hardened oil 3.00
10 Squalane 4.00
11 Stearic acid 2.00
12 Cholesteryl hydroxystearate 0.50
13 Cetyl 2-ethylhexanoate 4.00
14 Polyoxyethylene hydrogenated castor oil 0.01
15 Glycerol monostearate 3.00
16 Potassium hydroxide 0.15
17 Sodium metaphosphate 0.01
18 Paraoxyansuccinate 0.30
19 Trisodium edetate 0.01
20 4-TERT-butyl-4'-methoxydibenzoylmethane 0.05
21 Diparamethoxycinnamate mono-2-ethylhexanoate glyceryl 0.05
22 Carboxyvinyl polymer 0.10
23 Green tea extract 0.10
24 Erythritol 0.50
25 Artemisia extract 1.00
26 Birch extract 0.50
27 Buttonpi extract 2.00
28 Tranexamic acid methylamide hydrochloride 0.90
29 Silica-coated zinc oxide 3.00
30 Purified water Residual 31 Fragrance Appropriate amount 32 Colorant Appropriate amount

Formulation Example 5: Cream 2
Another prescription example of the cream which mix | blended the active ingredient which exhibits the anti-aging effect based on this invention is shown.
No. Name Compounding amount 1 Methylpolysiloxane 2
2 Decamethylcyclopentasiloxane 10
3 Octamethylcyclotetrasiloxane 15
4 Polyoxyethylene / methylpolysiloxane copolymer 3
5 Government-designated denatured alcohol 2
6 Isopropanol 1
7 Nouglycerin 3
8 Dipropylene glycol 5
9 Polyethylene glycol 6000 1
10 Sodium metaphosphate 0.05
11 Paraoxybenzoic acid ester 0.3
12 Trisodium edetate 0.05
13 Sodium hydroxymethoxybenzophenone sulfonate 0.01
14 Methyl bis (trimethylsiloxy) trimethoxycinnamate
Silyl isopentyl 0.1
15 Dimethyl distearyl ammonium hectorite 1.5
16 Polyvinyl alcohol 0.5
17 Hydroxyethyl cellulose 0.5
18 Trimethylsiloxysilicic acid 2
19 Loquat extract 0.5
20 L-Arginine 0.5
21 Active yeast extract 0.5
22 Colladecabaro extract 0.1
23 L-serine 0.1
24 Tranexamic acid ethylamide acetate 1.0
25 Purified water Residual 26 Fragrance appropriate amount 27 Colorant appropriate amount

Formulation Example 6: Gel A formulation example of a gel containing an active ingredient exhibiting an anti-aging effect according to the present invention will be shown.
No. Name Compounding amount 1 Polyoxyethylene / methylpolysiloxane copolymer 5
2 Dipropylene glycol 3
3 1,3-butylene glycol 10
4 Polyethylene glycol 1500 1
5 Polyoxyethylene methyl glucoside 1
6 Polyethylene glycol diisostearate 5
7 Potassium hydroxide 0.3
8 Paraoxybenzoic acid ester 0.2
9 Edetic acid-3Na 0.05
10 Hydroxypropyl methylcellulose 1
11 Carboxyvinyl polymer 0.5
12 Coriander extract 0.5
13 Altea extract 0.5
14 Peonies extract 0.5
15 Melissa Extract 1
16 Oil-soluble licorice extract 1
17 Tranexamic acid ethylamide phosphate 0.8
18 Purified water Residual 19 Perfume appropriate amount 20 Colorant appropriate amount

Formulation Example 7: Peel-off mask A formulation example of a peel-off mask containing an active ingredient that exhibits an anti-aging effect according to the present invention is shown.
No. Name Compounding amount 1 Glycerin 3
2 1,3-butylene glycol 8
3 Polyethylene glycol 1500 2
4 Citric acid 0.1
5 Sodium citrate 0.2
6 KOH 0.05
7 Sodium metaphosphate 0.01
8 Paraoxybenzoic acid ester 0.15
9 Xanthan gum 0.05
10 Carboxyvinyl polymer 0.15
11 Ages Extract 0.1
12 Ogon Extract 0.5
13 Active yeast extract 0.5
14 Glutathione 0.1
15 Tranexamic acid benzylamide sulfate 0.5
16 Oxide subsalt 1.0
17 Purified water Residual 18 Perfume appropriate amount 19 Coloring material appropriate amount

  INDUSTRIAL APPLICABILITY According to the present invention, an anti-aging agent, particularly a skin external preparation effective for suppressing wrinkle formation due to drying and / or improving wrinkles formed is provided.

Claims (7)

  An anti-aging agent for preventing wrinkle formation by drying and / or improving wrinkles formed, comprising a prourokinase activation inhibitor and / or a urokinase inhibitor as an active ingredient.   An anti-aging agent for preventing wrinkle formation by drying and / or improving wrinkles formed, comprising a prourokinase activation inhibitor as an active ingredient. The prourokinase activation inhibitor is one or more selected from the group consisting of amides of tranexamic acid represented by the following general formula (1) and cosmetically acceptable salts thereof: An anti-aging agent according to claim 1 or 2, characterized in that:

(Wherein R ₁ and R ₂ represent a hydrogen atom, a linear or branched alkyl group having 1 to 18 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms, a benzyl group, or the following general formula (2); R ₁ and R ₂ may be the same or different.

[Wherein, X represents a lower alkyl group, a lower alkoxy group, a hydroxy group, an amino group, or a halogen atom, and n = 0 to 3. ]).   The urokinase inhibitor is one or more selected from the group consisting of amiloride, zinc oxide, and a complex of zinc oxide and other inorganic or organic compounds. The anti-aging agent of any one of Claims.   A method for preventing wrinkle formation and / or improving wrinkles formed by drying, characterized by inhibiting the activation of prourokinase and / or inhibiting the activity of urokinase.   A method for preventing wrinkle formation by drying and / or improving wrinkles formed, which comprises inhibiting activation of prourokinase. Inhibiting the activation of the prourokinase is one or more selected from the group consisting of amides of tranexamic acid represented by the following general formula (1) and cosmetically acceptable salts thereof: The method according to claim 5 or 6, which is achieved by applying to:

(Wherein R ₁ and R ₂ represent a hydrogen atom, a linear or branched alkyl group having 1 to 18 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms, a benzyl group, or the following general formula (2); R ₁ and R ₂ may be the same or different.

[Wherein, X represents a lower alkyl group, a lower alkoxy group, a hydroxy group, an amino group, or a halogen atom, and n = 0 to 3. ]).