JP4488933B2 - Wrinkle improving agent and external composition for skin - Google Patents

Description

  The present invention relates to a wrinkle improving agent which has an excellent effect of improving wrinkles generated at an exposed site with aging, and has an effect of keeping the skin in a dermatological and cosmetically healthy state.

  Organs of all living organisms including humans are born and grow, then gradually decline with age, eventually stop functioning, and die when a certain part of the function is stopped. A state in which the function gradually declines is called aging. The skin is directly affected by the surrounding environment, and since it has an important function to maintain the environment inside the living body, it is unlikely that everything will stop functioning, but aging such as wrinkles, spots, dullness, tarmi, etc. This is an organ in which signs are easily manifested, and is particularly prominent in exposed areas exposed to sunlight.

  As skin aging progresses, defense against stimuli such as oxidative stress is weakened, causing the internal environment of the skin to be disturbed and further aging. In particular, since the exposed part is constantly exposed to strong oxidative stress caused by ultraviolet irradiation or the like, the progress of aging is remarkable. Such skin changes are called photoaging. In such skin, collagen, which is a constituent component of the majority of the dermis, decreases, and wrinkles deepen and become larger on the skin surface. No state.

  In the United States, retinoic acid is used as a prescription drug as a substance that has an improvement effect on wrinkles caused by the progress of photoaging, but it has not been approved in Japan because of its side effects and safety issues. . In addition, retinol (vitamin A), which is said to be converted into retinoic acid after being absorbed into the body and exert its effect, ascorbic acid (vitamin C) having an antioxidant and collagen synthesis promoting effect, and tocopherol having a strong antioxidant effect ( Vitamin E) and the like have been proposed as wrinkle-improving substances, but these have the disadvantage that a satisfactory effect cannot be obtained. In addition, antioxidants and anti-inflammatory agents used in pharmaceuticals, quasi-drugs, and cosmetics have not been able to obtain sufficient effects to improve wrinkles. In other words, none of the substances that have improved wrinkles so far has a sufficiently satisfactory effect and safety.

  Further, many conventional wrinkle improving agents are obtained by chemical synthesis, and there are many problems in terms of safety. On the other hand, natural substances that are less likely to cause safety problems are hardly known except vitamins, and those that are sufficiently effective have not been obtained. Furthermore, many natural wrinkle-improving agents such as retinol lack light stability, and even if they have an effect, there are substances that are difficult to be incorporated into the formulation, such as being rapidly degraded in the formulation. It was almost.

  Palmitic acid tyrosol ester is a known substance contained in the aroma component of the flower of the genus Obotaria (Non-patent Document 1). Among the fatty acid esters of tyrosol, those having 8 carbon atoms are contained in the specific fraction of sake (Non-patent Document 2, Patent Document 1). Furthermore, Patent Document 1 proposes that tyrosol fatty acid ester is used as an inhibitor of lipid metabolism enzymes. However, no study has been made on the wrinkle improvement effect.

JP 2003-26636 A Toshio Yamaguchi, Tohoku Pharmaceutical University Annual Report, Vol. 42, p105-108, 1995 Shin Ohura, Journal of Biotechnology, Vol. 81, No. 12, p514, 2003

  The object of the present invention is to improve wrinkles that are remarkably manifested in aging, especially in exposed areas, to keep skin healthy and cosmetically, and to improve wrinkles. Is to provide.

  As a result of intensive research in view of the above, the present inventors have improved the wrinkles that appear prominently at the exposed site, especially by the aging of fatty acid esters of tyrosol, especially palmitic acid esters, and cosmetically. The present invention has been completed by confirming that the effect of keeping the skin healthy and the safety and stability are excellent. That is, the first invention of the present application resides in a wrinkle improving agent characterized by containing a fatty acid ester of tyrosol represented by the following chemical formula (1).

（式中、ｎは１０〜１８の整数を表す。）

(In the formula, n represents an integer of 10 to 18.)

  The second invention of the present application is the above wrinkle improving agent, wherein the fatty acid ester of tyrosol is tyrosol palmitate.

  Furthermore, a third invention of the present application lies in an external composition for skin characterized by blending a fatty acid ester of tyrosol represented by the following chemical formula (1).

（式中、ｎは１０〜１８の整数を表す。）

(In the formula, n represents an integer of 10 to 18.)

  INDUSTRIAL APPLICABILITY The present invention can provide a wrinkle improving agent that is excellent in improving wrinkles that occur particularly in exposed areas with aging and that keeps the skin in a dermatological and cosmetically healthy state.

The present invention is described in detail below. As described above, it is known that the fatty acid ester of tyrosol used in the present invention is contained in the aroma component of the flower of the giant plant. However, since the content in the fragrance component is small, the production by purification and isolation is very poor in industrial efficiency. Therefore, it is desirable to use a general chemical reaction in the method for producing a fatty acid ester of tyrosol used in the present invention. Further, the method is not particularly limited.

  The fatty acid ester of tyrosol of the present invention has an effect of improving wrinkles particularly generated at an exposed site with aging, and it is possible to provide an excellent wrinkle improving agent by blending the fatty acid ester of tyrosol. . In particular, in the chemical formula (1), tyrosol palmitate, which is a fatty acid ester when n is 14, is particularly effective in improving wrinkles and is preferably used in the present invention.

  The amount of the fatty acid ester of tyrosol as a wrinkle improving agent is preferably 0.001 to 20.0% by mass (hereinafter, simply referred to as%), particularly preferably 0.00%, based on the total amount of the wrinkle improving agent. 5 to 5.0%. If the blending amount is less than 0.001, the intended effect of improving wrinkles is not sufficient. On the other hand, even if blending over 20.0%, the effect commensurate with the increase is not preferred.

  Further, the fatty acid ester of tyrosol of the present invention is blended not only in skin cosmetics but also in skin external compositions such as pharmaceuticals and bath additives for the purpose of improving wrinkles. Examples of the dosage form include lotions, emulsions, creams, packs and the like. In particular, tyrosol palmitate has a high wrinkle improving effect, and is preferably blended in a composition for external use on the skin.

  The amount of the fatty acid ester of tyrosol in the external composition for skin of the present invention is preferably 0.001 to 20.0%, particularly preferably 0.5 to 5.0%, based on the total amount of the external composition for skin. is there. Within this range, the wrinkle improvement effect can be exhibited remarkably. In addition, the composition for external use of the present invention achieves the object of the present invention with components usually blended in the composition for external use of skin, such as pigments, fragrances, preservatives, surfactants, pigments, antioxidants and the like. It can mix | blend suitably within the range.

  Hereinafter, the present invention will be described with specific examples, but the present invention is not limited thereto. In addition,% of the compounding quantity in an Example is mass% altogether.

Production Example 1 (Production of Tyrosol Palmitate)
Tyrosol (5.0 g) is placed in a 200 ml eggplant type flask, and 100 ml of anhydrous ether is added. Further, 1.0 ml of pyridine and 12.0 g of palmitic acid chloride were sequentially added. After stirring for a whole day and night, after-treatment was performed according to a conventional method to obtain 7.5 g of a crude product. The obtained product was fractionated by silica gel chromatography (ethyl acetate / chloroform (1: 4)) using silica gel 60N (100-210 μm) manufactured by Kanto Chemical Co., to obtain 3.5 g of tyrosol palmitate.

(Identification of tyrosol palmitate)
The purified tyrosol palmitate was confirmed by ¹³ C-NMR (100 MHz, CDCl ₃ ), and the following results were obtained.

^{By 13} C-NMR (100 MHz, CDCl ³ ), the following signal [δ (ppm): 14.1, 22.7, 24.8, 25.0, 29.3, 29.4, 29.5, 29. 6, 29.7, 32.0, 33.7, 34.4, 34.4, 65.0, 115.4, 130.0, 130.0, 154.4, 174.0] were detected ( (See FIG. 1).

Example 1 (wrinkle improving agent containing tyrosol palmitate)
The wrinkle improving effect when a wrinkle improving agent containing 1.0% tyrosol palmitate was applied to photoaged skin was examined by the following test method.

(Test method)
1. Test animals A group of 10 hairless mice aged 10 weeks at the start of the test was used.

2. 2. Evaluation method of wrinkle improvement effect 2-1. Photoaging conditions Photoaging was induced by irradiating UVA and UVB once a day, 5 times a week for 8 weeks. Irradiation dose, UVA is increased with ^{20J / cm 2, 25J / cm} 2, 30J / cm 2, UVB is ^{20mJ / cm 2, 30mJ / cm} 2, 40mJ / cm 2, an irradiation amount for each 1 week, 3 After week, the maximum dose was irradiated.

2-2. Evaluation method The wrinkle improvement effect was evaluated by the wrinkle score and the amount of dermal collagen.

  Wrinkle score: scored according to the method of Bissett et al. (Photochem Photobiol: 46, p367-378, 1987). That is, the size and depth of the wrinkle are comprehensively evaluated with the naked eye, 3 indicating “large and deep wrinkles can be confirmed”, 2 indicating “can check wrinkles”, 1 indicating “cannot check wrinkles”, and “normal” The texture is observed "was scored on a scale of 0 and 4.

Dermal collagen amount: All skin layers are collected and crushed with a Polytron homogenizer (KINEMATICA), then the collagen fraction is extracted, acid hydrolyzed, and the hydroxyproline content is determined using an amino acid analyzer (manufactured by JASCO). And quantified. The amount of hydroxyproline per cm ² was used as a relative indicator of the amount of dermal collagen.

3. Test Procedure A sample was prepared by mixing 1.0% of Tyrosol palmitate of Production Example 1 with a 50% ethanol aqueous solution (base) (Example 1). A sample containing only the base was used as Comparative Example 1. An evaluation sample (0.1 mL) was applied to the back skin (diameter: about 2.5 cm) of a hairless mouse once a day at a frequency of 5 times a week from the fifth week after the start of UV irradiation to the fourth week after the end of irradiation. . And after completion | finish of the last application, the wrinkle score was scored. After sacrifice, the skin was collected and the dermis collagen content (hydroxyproline amount per cm ² ) was measured.

(Test results)
The wrinkle improvement effect (wrinkle score value, dermal collagen content) when the wrinkle improving agent of Example 1 was applied was evaluated by comparing it with that applied with Comparative Example 1 containing only the base.

(Wrinkle score evaluation result)
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Group Wrinkle score value Significant difference
(Average value ± SE) (Comparative base)
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Example 1 (tyrosol palmitate) 2.35 ± 0.12 (P <0.01)
Comparative Example 1 (base only) 2.75 ± 0.19
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The tyrosol palmitate application group of Example 1 is compared with the application group of Comparative Example 1 with only the base,
The wrinkle score value was significantly low, indicating that tyrosol palmitate was effective.

(Results of measuring the amount of dermal collagen)
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Group Amount of hydroxyproline (mean ± SE)
(Μmol / cm ² )
―――――――――――――――――――――――――――――――――――
Example 1 (tyrosol palmitate) 6.65 ± 1.00
Comparative Example 1 (base only) 5.69 ± 0.28
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  The Tyrosol palmitate application group of Example 1 shows a higher collagen content (hydroxyproline amount) than Comparative Example 1 with only the base, and Tyrosol palmitate is less than the amount of dermal collagen that decreases due to photoaging. It was shown to be effective.

  From the results of this test, it can be seen that the wrinkle improving agent containing Example 1 tyrosol palmitate has an effect of improving wrinkles due to photoaging as compared with Comparative Example 1.

Example 2, Comparative Example 2 (skin lotion)
A skin lotion (Example 2) having the following composition was prepared according to a conventional method, and the wrinkle improvement effect was evaluated by using the sample as a sample by the following operation. In addition, the skin lotion which does not mix | blend the component (7) tyrosol palmitate was made into the comparative example 2. 10 healthy skin wrinkles (female, 40-70 years old) as subjects were determined for each of the skin lotions of Example 2 and Comparative Example 2 to the left or right, after face washing in the morning and after bathing in the evening 2 times a day for 2 months (60 days), about 0.2 ml each was applied to the wrinkles of the eye corners (about 4 cm ² , 2 × 2 cm centered around the eye corners). Then, after the final application, they were asked to answer a questionnaire regarding the condition of the skin (wrinkles) on the left and right eye corners.

(composition)
Ingredients Component Blending amount (%)
(1) Butylene glycol 30.0
(2) Monolauric acid 0.5
Polyoxyethylene (20) sorbitan
(3) Propylene glycol 20.0
(4) Glycerin 10.0
(5) Methylparaben 0.1
(6) Ethanol 7.0
(7) Tyrosol palmitate (Production Example 1) 1.0
(8) Purified water balance

  Based on the questionnaire results, the number of people who answered that the skin lotion of Example 2 is more effective than Comparative Example 2 for each item related to the state of skin (wrinkles) is shown below.

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Item Number of people
――――――――――――――――――
Wrinkles are less noticeable 7
The skin became soft 4
The skin got firmer 6
Shining on the skin 4
My skin became moist 3
――――――――――――――――――

  From this test result, it can be seen that the skin lotion of Example 2 clearly improved the wrinkles as compared with Comparative Example 2, and further improved the flexibility and color tone deteriorated by photoaging. Wrinkles formed on the human face appear as a result of repeated exposure to ultraviolet rays that do not cause inflammation repeatedly over a long period of time, and it is considered impossible to improve wrinkles with a simple anti-inflammatory action. In addition, skin abnormalities such as irritation and itching due to the skin lotion of the present invention were not observed.

Example 3 (skin cream)
Skin cream containing tyrosol palmitate with the following composition was prepared in the usual way, and 20 healthy people (women, 50-55 years old) who listed wrinkles in the corners of their eyes as a skin problem in a preliminary questionnaire were used for over a week. , Conducted a questionnaire survey.

(composition)
Ingredients Component Blending (%)
(1) Beeswax 2.0
(2) Stearic acid 5.0
(3) Stearyl alcohol 5.0
(4) Reduced lanolin 2.0
(5) Squalene 20.0
(6) Sorbitan monostearate 3.0
(7) Monostearic acid 3.0
Polyoxyethylene (20) sorbitan
(8) Propylene glycol 5.0
(9) Methylparaben 0.2
(10) Residual amount of purified water
(11) Tyrosol palmitate (Production Example 1) 1.0
(12) Fragrance appropriate amount

  A questionnaire survey was conducted using the skin cream of Example 3. The results are shown below. In addition, the result was shown by the number of people who responded that they thought so after use compared to before use for each item.

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Item Number of people
――――――――――――――――――
Wrinkles are less noticeable 16
Wrinkle size decreased 15
Number of wrinkles decreased 6
Increased wrinkles 0
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  From this test result, the skin cream of Example 3 is almost all humans who feel that wrinkles are less noticeable than before use, and the factor is that the size of wrinkles is reduced rather than the number of wrinkles. It can be seen that wrinkles due to photoaging were improved. In addition, skin abnormalities such as irritation and itching due to the skin cream of the present invention were not observed.

  In addition to skin cosmetics, it can be applied to medicines and baths as external preparations, and can be formulated into lotions, emulsions, creams, packs, etc. It is very useful from the aspect.

1 is a diagram showing a ¹³ C-NMR spectrum (100 MHz, CDCl ₃ ) of tyrosol palmitate of Production Example 1. FIG.

Claims (2)

A wrinkle improving agent comprising a fatty acid ester of tyrosol represented by the following chemical formula (1).

(In the formula, n represents an integer of 10 to 18.)   2. The wrinkle improving agent according to claim 1, wherein the fatty acid ester of tyrosol is tyrosol palmitate.

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