KR20100120585A - Composition for skin external application containing (all-cis)-11,14,17-eicosatrienoic acid - Google Patents

Abstract

PURPOSE: A composition of external use skin formulation for anti-aging and moisturizing is provided to suppress MMP(matrix metalloprotease) increase. CONSTITUTION: A composition of external use skin formulation contains 0.001-10 weight% of 11,14,17-Eicosatrienoic acid(ETA) as an active ingredient. ETA is contained in oil phase. The composition is used for preventing aging through reduction of collagenase expression. The composition is also used for skin moisturizing by suppressing skin barrier damage.

Description

Composition for skin external application containing (All-cis) -11,14,17-Eicosatrienoic acid}

The present invention relates to an anti-aging and moisturizing skin external preparation composition, and more particularly, ETA [(All-cis) -11,14,17-Eicosatrienoic acid, 20: 3n-3] in omega-3 fatty acids is effective. Containing ingredients as a component inhibits skin loss due to increased skin barrier damage due to decreased protective function due to external stimulation and increases in collagen breakdown enzymes (MMP: matrix metalloprotease). It relates to an anti-aging and moisturizing external preparation composition having an effect.

The skin acts as a defense against physicochemical irritation and invasion of microorganisms between the external environment and the living organs in the body. The defense function of the skin is mainly performed by the stratum corneum, the outermost layer of the skin, and the fat film of the skin assists with assistance. Maintaining an appropriate amount of moisture in the stratum corneum is very important for maintaining the elasticity and flexibility of the skin. Normal skin contains about 30% water or water-soluble components. If the water content in the stratum corneum falls below 10%, dry skin may develop, resulting in cracked or rough skin.

Dividing the factors that weaken the barrier function of the skin into internal factors and external factors include internal diseases such as disease, genetic defects and aging, external factors such as the use of soap or detergent, UV rays, warm and hot conditions Prolonged exposure in a humid environment and poor eating habits. Due to these internal and external factors, the stratum corneum, which acts as a barrier, structurally and physiologically degenerates, thus weakening the defense function. Therefore, maintaining proper moisture so that the moisture of the stratum corneum does not fall below the proper level is essential and essential to skin physiology.

In addition, the collagen of the dermis is an important fibrous protein, which accounts for about 25% of the total protein of the human body, an important component of extracellular matrix and occupies most of connective tissue. Collagen accounts for about 75% of dry skin weight and about 90% of dermal fiber, and plays an important role in providing an intercellular matrix, structural support, and providing skin's tensile strength. If left uncontrolled, it is a major cause of skin aging, including decreased skin elasticity and wrinkles (M. Tzaphlidou, Micron 35: 173 (2004)). In addition, matrix metalloprotease (MMP) has been reported to be increased by ultraviolet light, which is known to promote collagen breakdown and cause deformation of the dermal layer.

In the early 1970s, the Eskimos living in Greenland had been studying their diet since it was known that they had few blood-related diseases such as heart disease, cancer and diabetes. They found that they eat more than twice a day of deep-sea fish, mainly seal meat and small whales, and they continued to study the omega-3 (w-3) fatty acids in their food. In the 1980s, the general impact of polyunsaturated fatty acids (PUFA) and in particular the study of omega-3 fatty acids were intensively studied, and these days it is known that unsaturated fatty acids are essential for normal growth and development. It has been reported to play an important role in the prevention and treatment of diseases such as coronary artery disease, hypertension, arthritis, autoimmune disorders and cancer.

Omega-3 fatty acids can be broadly divided into eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and ETA (11,14,17-Eicosatrienoic acid), which provide a pathway for the biochemical action of the human body and actually all the metabolism of the body. Affect the process It also plays a key role in maintaining proper cell structure, including surrounding cells and protecting them. One of the important functions of omega-3 is to help the body absorb the various substances from the tissues that are the basic units of the body, process them, filter them and send them to the destination required by each element of the body. In other words, the omega-3 contained in the cell membrane opens the door of the cell to enter the substance, and also acts as a gatekeeper that processes the substance and sends it to each part of the body and then closes the cell door.

Until now, research on the role of omega-3 fatty acids, known as healthy ingredients, in the skin has been focused on EPA.

Therefore, the present inventors have found that ETA is specifically reduced in omega-3 fatty acids in elderly skin by studying quantitative changes in omega-3 fatty acids in human skin, and treated ETA after irradiating UV rays to skin cells and mice. When the present invention was completed, the present invention has been found to not only improve skin wrinkles but also to prevent damage to the skin barrier, thereby preventing evaporation of moisture in the skin.

Accordingly, it is an object of the present invention to provide a skin anti-aging and moisturizing external preparation composition that prevents skin damage caused by ultraviolet rays and prevents loss of moisture due to skin barrier damage.

In order to achieve the above object, the present invention provides an external composition for skin containing 11,14,17-eicosartic acid as an active ingredient.

The external preparation composition for skin according to the present invention showed a significant effect on improving skin wrinkles and elasticity by inhibiting the production of MMP by ultraviolet rays, and exhibited a moisturizing effect by preventing a decrease in moisture loss of the epidermis through reduction of skin barrier damage. In addition, ETA used as an active ingredient in the present invention was confirmed to have excellent stability in the formulation and skin safety than 11,14,17-eicosatriic acid ester in the product.

Reduction of ETA in UV or aged skin decreases the protective function caused by external stimuli and increases skin barrier damage, resulting in loss of water content, as well as an increase in the amount of matrix metalloproteinase, a collagen degrading enzyme caused by UV.

Therefore, in the present invention, in order to prevent skin aging or to prevent skin aging by preventing ETA reduction caused by ultraviolet rays and aging, the present invention has an effect of promoting recovery of skin barrier damage and suppressing expression of matrix metalloprotease. Provided is an external composition for skin containing ETA represented by the following Chemical Formula 1 as an active ingredient:

In the present invention, an oil form containing an omega-3 fatty acid including ETA may be used, but is not limited thereto. In addition, ETA used as an active ingredient in the present invention is characterized in that the stability and skin safety in the formulation than 11,14,17-eicosatriic acid ester.

That is, in one embodiment of the present invention provides an external composition for skin to give a skin moisturizing effect by increasing the amount of skin moisture by restoring and strengthening the skin barrier damaged and collapsed by ultraviolet light.

In addition, one embodiment of the present invention provides a skin external composition for preventing skin aging by protecting the skin from external harmful environment and inhibiting the expression of MMP to prevent damage to the dermal layer.

In another embodiment, the present invention provides a topical skin composition for inhibiting the inflammatory response to protect the skin from harmful factors in the skin.

The external preparation composition for skin according to the present invention, based on in vitro and in vivo experiments, contains ETA in an amount of 0.001 to 10 wt%, preferably 0.01 to 5 wt%, based on the total weight of the external preparation composition for skin. good.

The external preparation composition for skin according to the present invention is not particularly limited in its formulation, and includes, for example, a cosmetic composition having a formulation of supple cosmetics, nourishing cosmetics, massage cream, nourishing cream, pack, gel or skin adhesive type cosmetic; Or in the form of transdermal dosage forms such as lotions, ointments, gels, creams, patches or sprays. In addition, in the external preparation composition of each formulation, other components than the essential components described above can be appropriately selected and blended by those skilled in the art without difficulty according to the formulation or purpose of use of other external preparations.

Hereinafter, the content of the present invention will be described in more detail through Examples and Test Examples. These examples are provided only for understanding the contents of the present invention, and the scope of the present invention is not limited to these examples, and modifications, substitutions, and insertions commonly known in the art may be performed. This is also included in the scope of the present invention.

Test Example 1 Lipid Analysis (GAG chromatogtaphy)

Presented on each skin after biopsy of young skin (20s-30s, 5 males, average age 32) and aged skin (3 males 60s-70s, 3 males, 68 years old) C16: 0 (palmitinic acid), C16: 1 (palmitoreic acid), C18: 0 (stearic acid), C18: 1n9 (oleic acid: 9-cis-octadecanoic acid), C18: 2n6 (linoleic: 9,12 The contents of cis-octadecadienoic acid (9,12-cis-octadecadienoic acid) and C20: 3n3 (ETA) were analyzed to observe the change in lipids with age.

Homogenized skin tissue was placed in 200 µl of chloroform: methanol = 1: 1 (v / v) extract and vortexed for 30 minutes. 200 μl of the extract was added to the mixed solution of the tissue and the extract, followed by centrifugation, only the chloroform layer was separated, and the separated chloroform layer was evaporated and analyzed by GC chromatography. The results are shown in FIG. 1. .

In the results of FIG. 1, palmitoleic acid and oleic acid were increased in the aged skin tissue among the fatty acids, while ETA (C20: 3n3) was significantly decreased. This phenomenon is caused by changes in the lipogenic enzymes involved in lipid metabolism. In particular, the treatment of palmitoleic acid and oleic acid in skin cells tended to promote aging. In addition, it was confirmed that ETA can act as a skin aging factor through the significant decrease in ETA in elderly skin tissues.

Test Example 2 Changes in MMP-1 Expression Levels According to ETA Treatment in Keratinogenesis

Human keratinocytes were placed in 100 mm dishes at a concentration of 10 ⁶ , incubated at 37 ° C. in DMEM medium containing 10% fetal calf serum, and then treated with ETA 5 and 10 μM, respectively. After 24 hours of culture, cell cultures were obtained, and the amount of MMP-1 expression was compared with the negative control group not treated with ETA according to the Western blot method, and the results are shown in FIG. 2.

In the results of FIG. 2, it was confirmed that the expression level of MMP-1, a collagen degrading enzyme, was significantly reduced when compared to the negative control group not treated with ETA.

Test Example 3 Changes in Water Evaporation Rate after ETA Treatment after Skin Barrier Damage

After repeatedly applying 0.1 and 1% by weight of ETA to the back of the hairless mice (8-10 weeks old), the barrier function was tested for damage. Transepidermal water loss (TEWL) was measured with EP1, an evaporimeter from Servaed, Sweden, and when the vehicle reached 40 g / m2 / h, vehicle (propylene glycol: ethanol = 7: 3, ETA) The amount of barrier function is evaluated by evaluating the extent to which the epidermal moisture loss is reduced by applying a sample containing the substance to the group (V)) twice a day at 200 μl in an area of 5 cm 2. In addition, after the skin barrier damage caused by ultraviolet (100 mJ = 1MED) irradiation was measured epidermal moisture loss, the results are shown in FIG.

In the results of Figure 3, the amount of water evaporation was reduced compared to the control according to the concentration after the ETA treatment, it was confirmed that the amount of water evaporation increased after the ultraviolet irradiation also decreases with the ETA treatment.

Formulation Example 1 and Comparative Formulation Examples 1 and 2

The emulsions of Formulation Example 1 and Comparative Formulation Examples 1 and 2 were prepared in a conventional manner according to the compositions shown in Table 1 below (unit: wt%).

Compounding ingredient Formulation Example 1 Comparative Formulation Example 1 Comparative Formulation Example 2 Purified water Balance Balance Balance 11,14,17- Eicosatrienoic Acid (ETA) 0.1 - 11,14,17-Eicosatrienoic Acid Ester - 0.1 - Vegetable Cured Oil 1.5 1.5 1.5 Stearic acid 0.6 0.6 0.6 Glycerol Stearate 1.0 1.0 1.0 Stearyl alcohol 2.5 2.5 2.5 Polyglyceryl-10 pentastearate,
Behenyl Alcohol &
Sodium Stearoyl Lactylate 1.0 1.0 1.0 Arakidil Behenyl Alcohol &
Arachidil Glucoside 1.0 1.0 1.0 Cetylaryl Alcohol &
Cetearylglucoside 2.0 2.0 2.0 PEG-100 stearate,
Glycerol Olate &
Propylene glycol 1.5 1.5 1.5 Caprylic / Capric Triglycerides 11.0 11.0 11.0 Cyclomethicone 6.0 0.6 6.0 Preservative, incense Quantity Quantity Quantity Triethanolamine 0.1 0.1 0.1

[Test Example 4] Wrinkle improvement effect using a photo-aging animal model of hairless mice

In order to determine the actual skin wrinkle improvement effect, the application test was carried out using about 7 weeks old hairless mouse (SKH-1 female hairless mouse). Formulation Example 1 and Comparative Formulation Examples 1 and 2 were applied to the back of the hairless mice for 11 weeks with UV irradiation. Ultraviolet irradiation every other day, the test material was applied every day, and then the effect of wrinkle improvement (R1: largest wrinkles and R3: average wrinkles) was confirmed by a replica wrinkle analysis method. 4 is shown.

In the results of Figure 4, in the experimental group coated with Formulation Example 1 containing ETA as an active ingredient, not only the largest wrinkle but also the average value of the wrinkles was reduced to confirm that the skin wrinkle improvement effect is significantly superior to Comparative Formulation Examples 1-2. Could.

Test Example 6 Inhibitory Effect of Cyclooxygenase-2 (COX-2: cyclooxygenase-2) on Microinflammatory Factors

In Experimental Example 5, after irradiation with ultraviolet light, the backs of the hairless mice at the wrinkles region were biopsied to quantify the amount of cyclooxygenase-2 produced using the Western blot method. As a result, a comparison value measured by a densitometer with an ultraviolet control group of 100 is shown in Table 2 and FIG. 5.

Test substance COX-2 biosynthesis (%) Average N = 1 N = 2 Formulation Example 1 50 34 42 Comparative Formulation Example 1 80 75 77.5 Comparative Formulation Example 2 100 100 100

From the results of Table 2 and FIG. 5, Formulation Example 1 containing ETA according to the present invention as an active ingredient concentration-dependently reduced the biosynthesis of cyclooxygenase-2 by ultraviolet rays to produce prostaglandin E2 (product of COX-2). It was found that skin eruption, pain and degradation by PGE ₂ ) can be prevented.

Test Example 7 Evaluation of Stability in Formulations

In order to determine the stability of the two compounds of ETA and 11,14,17-eicosartic acid ester in the formulation, the stability of each formulation was measured under the harsh conditions of 25 ℃ and 40 ℃, the results are shown in Table 3 Shown in

Test substance Storage temperature Test result (% of initial value) At the time of manufacture after 2 weeks 4 weeks later Formulation Example 1 Room temperature 100
(91.9) 96.9 95.3 40 ℃ 96.3 93.6 Comparative Formulation Example 1 Room temperature 100
(89.2) 65% 40 40 ℃ 52% 10

In the results of Table 3, in the case of Formulation Example 1 containing ETA according to the present invention as an active ingredient, it was confirmed that the stability was maintained at 90% or more after 2 weeks and 4 weeks at 40 ° C. at room temperature and harsh conditions, while 11,14 In the case of Comparative Formulation Example 1 containing, 17-eicosatriic acid ester, it was hardly measured under severe conditions, and it was confirmed that the formulation stability was remarkably decreased.

Test Example 8 Skin Safety Evaluation

To evaluate the skin safety of two compounds, ETA and 11,14,17-eicosatriic acid ester, Formulation Example 1 and Comparative Formulation Example 1 were used to examine the general public (20 women, 20-45 years) with healthy skin. 1, 2, and 4 weeks after application to the face, the degree of stimulation was surveyed by +++ (severe)> ++ (severe> + (slightly)>-(none), etc. to objectify subjective judgment. The degree of stimulation was evaluated and the results are shown in Table 4 below.

Test substance Causes irritation (subjective assessment, +++ (high), ++ (medium),-(none) Number of people (20) 1 week 2 weeks 4 Weeks Formulation Example 1 20 people 0 people 0 people 1 point - - + Comparative Formulation Example 1 20 people 15 people 12 people 10 people +++ +++ ++

In the results of Table 4, it was confirmed that there is little irritation for the formulation example 1 containing the ETA according to the present invention, while 1 for the comparative formulation example 1 containing 11,14,17-eicosatriic acid ester In both weeks and 2 weeks, it was confirmed that a very severe stimulus was expressed as +++.

As described above, according to the results of Test Examples 3 to 4, ETA proposed in the present invention is effective in improving the moisturizing power by preventing the loss of moisture in the skin, and also reduces the expression of MMP-1 by ultraviolet rays, thereby improving wrinkles. It was found to be effective. The inhibitory effect of the skin barrier and collagen biosynthetic degrading enzyme is not only moisturizing, but also can improve skin wrinkles and elasticity and ultimately delay skin aging.

Therefore, the external preparation composition for skin containing ETA according to the present invention can be used as an effective substance for improving skin aging and skin moisturizing.

Figure 1 shows the results of observing lipid changes in the elderly and young human skin.

Figure 2 is a result showing the change in the amount of expression of MMP-1 according to the ETA treatment after irradiating ultraviolet light to keratinocytes.

3 is a graph showing changes in water evaporation amount according to ETA treatment after skin barrier damage and UV irradiation using hairless mice.

Figure 4 is a simulated plate analysis graph for analyzing whether there is an anti wrinkle effect by treating ETA to hairless mice.

5 is a result of observing the expression of COX-2 in order to determine whether the inflammatory response is suppressed after treatment with ETA in hairless mice.

Claims (5)

A skin external composition comprising 11,14,17-eicosatrienoic acid (11,14,17-Eicosatrienoic acid) as an active ingredient. The composition for external application for skin according to claim 1, wherein the 11,14,17-eicosatriic acid is contained in the form of an oil. The composition for applying the external of the skin according to claim 1, wherein the composition is for preventing skin aging through a decrease in the expression level of skin collagen degrading enzyme by ultraviolet rays. According to claim 1, wherein the composition is an external composition for skin, characterized in that for moisturizing the skin through inhibiting damage to the skin barrier. The composition for external application for skin according to claim 1, wherein the 11,14,17-eicosatriic acid is contained in an amount of 0.001 to 10% by weight based on the total weight of the total composition.

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