KR20040098878A - Cosmetic composition containing tranexamic acid stabilized with liquid crystalsome - Google Patents

Abstract

PURPOSE: Provided is a cosmetic composition containing tranexamic acid stabilized with liquid crystalsome which allows easy permeation of tranexamic acid into the skin, displays skin whitening effect by inhibiting melanogenesis and biosynthesizing collagen, as well as improves skin wrinkles. CONSTITUTION: The cosmetic composition for whitening the skin and improving skin wrinkles is characterized by containing 0.01-20. wt% of, preferably 0.001-20 wt.% of tranexamic acid stabilized with liquid crystalsome.

Description

Tranexamic acid-containing cosmetic composition stabilized with liquid crystalsome {COSMETIC COMPOSITION CONTAINING TRANEXAMIC ACID STABILIZED WITH LIQUID CRYSTALSOME}

The present invention relates to a cosmetic composition containing tranexamic acid, and more particularly, to a skin wrinkle improvement and whitening cosmetic composition containing the tranexamic acid stabilized by liquid crystal.

Liquid crystalsomes are a special kind of liposomes currently used in drug delivery systems to stabilize bioactive components in the pharmaceutical field.

Liposomes are generally made of phospholipids. These phospholipids consist of hydrophobic long hydrocarbon chains and hydrophilic polar groups, and the hydrophobic long hydrocarbons consist of sphingosin derivatives or glycerol derivatives. The other side has ester linkages with choline, ethanol amine, serine, inositol or glycerol. Phospholipids form these regularly arranged structures in the water medium, namely micelles or lamellar structures.

Liposomes are also similar in structure to biological membranes and are being studied as membrane model systems and physiological delivery media (R. Sundler. D. Papahadjpovlos, Biochim. Biophys. Acta, 648.743 (1981)). It is also widely used in cosmetics and food. Such liposomes can be delivered stably without breaking the physiologically active ingredient, and have the advantage of containing both the soluble and water-soluble physiologically active ingredients.

Liposomes are largely divided into MLV (Multilamella vesicle) and monolithic liposomes (ULV: Unilamella vesicle), and ULV can be divided into Large Unilamella vesicle and Small Uni lame lla vesicle. MLV is 400-3500 nm in size and 5-15% of the amount can be contained in liposomes. LUV has a size of 100-1,000 nm, 36-65% of the amount can be contained in liposomes, and SLV has a size of 20-50 nm, and 0.5-1.0% of the amount can be contained in liposomes. The amount of bioactive substances that can be contained is the most LUV but unstable, SLV is the most stable but the amount that can contain less. In addition, the structure of the human skin has a multi-layered structure, so MLV has affinity with the skin, but its size is so large that it is difficult to penetrate the skin.

On the other hand, the liquid crystalsomes have a size of 10-200 nm, are easy to penetrate the skin, can contain excessive amounts of water-soluble components, and are stable. In addition, in the components, liposomes are formed by phospholipids, while liquid crystalsomes form vesicles using lecithin, fatty alcohols, fatty acids, and the like, and contain the bioactive components in the vesicles to form active ingredients. Protects and facilitates penetration into the skin.

It is known that skin ages due to two mechanisms: internal aging, which is a natural aging process with age, and external aging, which is progressed by external factors. External aging plays a role of promoting internal aging as well as aging itself. The most important factor of external aging is ultraviolet light, which causes photo aging by ultraviolet light.

In photo-aged skin, the stratum corneum in the outermost layer of skin becomes thick while the thickness of the entire epidermal layer becomes thin, resulting in atrophy of the skin. In the dermal layer, which is located under the epidermal layer and composed of collagen fibers, elastic fibers, and hyaluronic acid, collagen fibers, which occupy most of the dermis, are denatured and destroyed by photoaging, and the activity of the fibrous cells that synthesize collagen is reduced. This decreases the synthesis of new collagen fibers. Elastic fibers show similar changes to collagen fibers, and hyaluronic acid, a major component of the extracellular matrix, is also reduced, resulting in impaired water retention in the dermis.

Due to these changes in the epidermis and dermis, the skin becomes rough and thin, loss of elasticity, dry skin caused by water loss and ultimately wrinkles.

Drugs that inhibit and treat such skin aging include sunscreen, tretinoin (vitamin A derivative), alpha hydroxy acid (AHA), and antioxidant (antioxidant).

On the other hand, the human skin color is determined by hemoglobin (hemoglobin), bilirubin (bile pigment) and melanin (skin pigment), but melanin is most affected. Melanin is synthesized in melanocytes (melanocytes) in the lower epidermis of skin cells, and when melanin is synthesized, an enzyme called tyrosinase acts on a substrate called tyrosine in melanocytes to produce dopaquinone. This dopaquinone becomes melanin through an oxidation reaction and an enzyme reaction. The enzyme tyrosinase, which acts as an important factor in the melanin production process, is further activated by ultraviolet rays, so that excessive exposure to sunlight causes melanin production, which is abnormally deposited in the skin, resulting in darkening of the skin, blemishes and mushrooms. Will be produced.

Therefore, the external preparation for skin whitening is prepared by combining a substance having an effect of inhibiting the activity of tyrosinase or inhibiting some reactions during the production of melanin, in particular, a substance which inhibits the activity of the tyrosinase. Typical examples of such substances include ascorbic acid, hydroquinone, arbutin, kojic acid, and the like.

As described above, products including anti-wrinkle formation and skin whitening substances for various anti-aging have been developed, but there are still many things to be improved in terms of efficacy and stability. The development of functional cosmetics for wrinkle improvement and skin whitening based on the result analysis is insufficient.

About tranexamic acid, the Journal of the Korean Academy of Oral Wounds (Journal of Korean Asspcoiation of Oral and Maxillifacual Surgeons, 1987, # 13, No. 1, P217, and P233) Dental Health 1998 1998 Volume 22 Volume 3 P205 P214 Moon Hyuk-su, The Journal of Korean Society of Anesthesiologist 1996 Volume 31 Volume 5 P6 신 P639 Shinchiman, Restoration of skin barrier function (J Invest Dermatol. 1997 Jul. 109 (1): 84-90.Denda M), skin wound healing enhancing effects (Int J Oral Maxillofac Surg. 1988 Aug; 17 (4): 275-6.Bjorlin G, Nilsson IM.) Comparative Study on Bleeding in Goat Treated with Anticoagulant (Journal of Korean Asspcoiation of Oral and Maxillifacual Surgeons, 1987, 13, Volume 1, Issue 1, P207, P216, OH. Invest Clin. 1998 Jun; 39 (2): 77-83. Spanish Bernardoni-Socorro C) has been studied. In the patent document related to Tranexamsan, a pre-formed gel sheet (Domestic Application Publication No. 1020027000213), a sheet-like device (Domestic Application Publication No. 1020027000208), a transdermal absorbent using polymer nanoparticles, and an external preparation composition containing the same (Domestic Application Publication) No. 1020010019869), cleaning products for skin and hair in which skin protection active ingredients are deposited (National Application Publication No. 1020007011848), preparation method of sustained-release microspheres by the multiple emulsion method (Domestic Application Publication No. 1020000036178), traneck A samsan (tranexsamic acid) derivative and a skin external preparation containing the same (Domestic Application Publication No. 1019947000952).

It is an object of the present invention to provide a skin wrinkle improvement and whitening cosmetic composition in which tranexamic acid is stabilized with liquid crystals, which is excellent in inhibiting melanin production and collagen biosynthesis.

1 is a melanin reduction graph according to Test Example 1,

Figure 2 is a cell proliferation graph according to Test Example 2.

In order to achieve this object, according to the present invention, characterized in that the liquid crystals containing the tranexamic acid containing 0.01 to 20.0% by weight relative to the total weight of the cosmetic composition, the liquid crystals stabilized Tranexamic acid-containing cosmetic composition This is provided.

The present invention is described in detail as follows.

Tranexamic acid can be used as it is, or can be used by dissolving in solvents, such as alcohol, such as methanol, 1, 3- butylene glycol, isopropyl alcohol, propylene glycol, and ethanol, and purified water.

In the case of using tranexamic acid dissolved in the above solvent, the solution is used as it is, or filtered under ultra-high frequency reduced pressure in a 40 kHz frequency region while heating at 80 to 90 ° C. to obtain a liquid sample, and then again in a vacuum concentrated flask of 600 to 900 mmHg. It can be used to concentrate the concentration of solids to 20-30% by pressure.

In order to protect and stabilize the Tranexamic acid components such as to penetrate the skin easy to be contained in the liquid crystal.

In the present invention, the size of the liquid crystalsome is 20 to 50nm, easy to penetrate the skin, and uses a stable liquid crystalsome while containing an excessive amount of water-soluble components.

These liquid crystals are prepared using a ceramide, hydrogenated lecithin, cetearyl alcohol, glyceryl monostearate, stearic acid, sphingolipid derivative, phytosterol, linoleic acid, linolenic acid, and then a vesicle (base). Tranexamic acid is added to the vesicle and homogenized by adding water and an emollient (cyclomethicone, cetyloxanolate) in this order.

At this time, ceramide, hydrogenated lecithin, cetearyl alcohol, glyceryl mono stearate, stearic acid, sphingolipid derivatives, phytosterol, linoleic acid, linolenic acid is 10 to 30% by weight based on the total weight of the tranexamic acid-containing liquid crystal It is contained in an amount of%, preferably 30% by weight. If the components are more than 30% by weight, the viscosity is too high to apply to the product, if less than 10% by weight, the viscosity is low and the particles are unstable and the stability of the product is excessively lowered.

The vesicle is prepared by heating the ceramide, hydrogenated lecithin, cetearyl alcohol, glyceryl monostearate, stearic acid, sphingolipid derivative, phytosterol, linoleic acid, linolenic acid to 80 ~ 85 ℃ completely mixed. .

The tranexamic acid is preferably added in an amount of 0.001 to 20% by weight, and particularly preferably 0.5 to 5.0% by weight, based on the total weight of the tranexamic acid-containing liquid crystal. If it is less than 0.001% by weight, there is little effect in application to the product, and if it exceeds 20% by weight, the active ingredient may come out without entering the liquid crystal base.

The obtained liquid crystals stabilized tranexamic acid can be added to the wrinkle-reducing and whitening-related cosmetics such as nourishing lotion, nourishing cream, essences, etc., it is preferred to add 0.01 to 20.0% by weight relative to the total weight of the composition. If it is less than 0.01% by weight, the efficacy is too small, and if it is more than 20.0% by weight, the feeling of use as a cosmetic is poor, which is not suitable for use in thin products such as lotions.

The following Examples, Comparative Examples, Preparation Examples, and Test Examples are provided to explain the present invention in more detail, and the scope of the present invention is not limited thereto.

(Example 1)

Preparation of Liquid Crystal Stains Stabilized with Tranexamic Acid

Tranexamic acid was purchased from Sigma-Aldrich A6516 (Sigma).

The A phase of the following Table 1 was measured, it heated to 80-85 degreeC, melt | dissolved and mixed completely, and then cooled while stirring gradually, and obtained solid shape (vecicle). The obtained solid base was heated to about 70 ° C. to melt, and then stirred while gradually adding tetranesamic acid (B phase) to allow the B phase to enter into the A phase. Phase D was added thereto and homogenized while raising the temperature to about 70 ° C. Subsequently, the C phase was raised to 70 ° C. and homogenized while gradually being added to the mixture of A, B and D phases. The components of the liquid crystal fragments stabilized in the obtained trinexamic acid are shown in Table 1 below.

(Comparative Example 1)

Preparation of liquid crystal

A liquid crystalsome was prepared in the same manner as in Example 1, except that phase B was not added.

(Test Example 1)

Melanin Production Inhibition Test

The melanin production inhibitory effect was measured with respect to the liquid crystalsome stabilized by the tranexamic acid of Example 1, the liquid crystalsome of the comparative example 1, and a tranexamic acid.

Melanocytes isolated from human tissues were primaryly cultured and passaged two times, and then cultured in 60 mm culture dishes at a concentration of 2 × 10 ⁴ cells / culture plate using RPMI 1640 medium. After confirming that the cells adhered to the dish, for Example 1, Comparative Example 1, and tranexamic acid, 0.0001% by weight, 0.001% by weight, 0.01% by weight, 0.1% by weight, 0.5% by weight, 1% by weight, 5% by weight Treatment was done by concentration up to%, 10%, 20% and 25% by weight. After 3 days of treatment, the cells were washed three times with PBS, and then cells were removed with trypsin-EDTA to uniformly distribute 2 × 10 ⁵ cells. 100 μl of 1N NaOH solution was added thereto and treated at 37 ° C. for 12 hours to completely lyse the cells. Absorbance was measured at 490 nm for 500 μl of cells in which cells were completely lysed. In addition, absorbance was measured using the extract-free treatment as a control.

As a standard indicator, 10 mg of synthetic melanin (M8601, manufactured by Sigma) was dissolved in 10 ml of 1N NaOH to prepare a mother solution (1 mg / ml), followed by 700 µg / ml, 300 µg / ml, 100 µg / ml, Dilutions of 70 µg / ml, 30 µg / ml, 10 µg / ml, 7 µg / ml, 3 µg / ml, 1 µg / ml and 0.1 µg / ml were prepared and the absorbance was measured at 490 nm.

Using the measured absorbance, the amount of melanin reduction was calculated according to the following equation.

The results are shown in Table 2 and FIG. 1.

In Table 2, the liquid crystalsomes stabilized in the tranexamic acid according to the present invention were much better melanin production inhibitory effect than when using the transexamic acid as it is or using only liquid crystals. In addition, it can be seen from the data for Example 1 of Table 2 that it is preferable to contain the liquid crystal bit containing the tranexamic acid 0.01% by weight to 20.0% by weight relative to the total weight of the cosmetic composition.

(Test Example 2)

Collagen Biosynthesis Effect

The collagen biosynthesis effect was measured with respect to the liquid crystalsome stabilized by the tranexamic acid of Example 1, the liquid crystalsome of the comparative example 1, and tranexamic acid.

Fibroblasts cultured in T-75 flasks were washed 2-3 times with PBS, and the adherent cells were dropped using trypsin, and the cells were collected by centrifugation (Heraeus; Labofuge 400R) at 1500 rpm for 5 minutes. After centrifugation, the supernatant was discarded, and 10 ml of DMEM (10% FBS) was added to the collected cells and mixed evenly. By measuring the number of cells using a hemocytometer, cells of about 10 ⁴ ea / well were dispensed into each 200-well well of 96 wells. After incubating at 37 ° C and 5% CO ₂ , about 50% of the well area grows and exchanges with fresh DMEM (FBS10%), and 0.001%, 0.001%, 0.01%, and 0.1% of tranexamic acid. Cells were incubated for 6, 12, 24, and 48 hours with concentrations up to, by weight, 0.5%, 1%, 5%, 10%, 20% and 25% by weight.

Collagen synthesis performance measurement kit (Procollagen Type-I C-peptide EIA kit (Takara, MK 101)) was used. For measurement using immunological methods, 100 μl of Ab-POD conjugate solution was transferred to one well and aliquoted, and 20 μl of cell culture or standard solution was added. The 96 well plate was wrapped with foil etc., and it incubated for 3 hours at 37 degreeC. After 3 hours, all the solutions in each well were removed and washed 4 times with PBS. After the washing step, 100 μl of substrate solution was added to each well and incubated at 20-30 ° C. for 15 minutes. In the final step, 100 µl of 1N H ₂ SO ₄ , the reaction termination solution, was added and mixed gently. The absorbance was measured with an ELISA reader and the result was used. After the reaction solution was added to the plate was stored for about 1 hour at room temperature and the absorbance was measured at 450nm.

Synthesis (%) was calculated according to the following equation, and the results are shown in Table 3 and FIG.

In Table 3, the liquid crystalsomes stabilized in the tranexamic acid according to the present invention had a much better collagen biosynthesis (cell proliferation) effect than the case of using only the netraxane liquid crystals. In addition, it can be seen from the data for Example 1 of Table 3 that it is preferable to contain the liquid crystal bit containing tranexamic acid 0.01% by weight to 20.0% by weight based on the total weight of the cosmetic composition.

(Manufacture example 1)

To mix the ingredients of Table 4 to prepare a nourishing cream.

(Comparative Production Example 1)

Instead of using the liquid crystals stabilized in the trexexane of Example 1, nutritional creams were prepared in the same manner as in Preparation Example 1, except that the liquid crystals of Comparative Example 1 were used.

(Manufacture example 2)

The lotion was prepared by mixing the ingredients of Table 5 below.

(Comparative Production Example 2)

A lotion was prepared in the same manner as in Preparation Example 2, except that the liquid crystalsome of Comparative Example 1 was used instead of the liquid crystalsome of Stanexane stabilized.

(Manufacture example 3)

The skin was prepared by mixing the ingredients of Table 6 below.

(Comparative Production Example 3)

Skin was prepared in the same manner as in Preparation Example 3, except that the liquid crystalsome of Comparative Example 1 was used instead of the liquid crystalsome of Stanic Samsanic Acid stabilized.

(Manufacture example 4)

The components of Table 7 were mixed to prepare concentrated cosmetic water (essence).

(Comparative Production Example 4)

Instead of using the liquid crystals stabilized with the trexexane of Example 1, a concentrated cosmetic water (essence) was prepared in the same manner as in Preparation Example 4, except that the liquid crystals of Comparative Example 1 were used.

(Test Example 3)

Whitening measurement human body test

In Preparation Examples 1 to 4 and Comparative Preparation Examples 1 to 4, eight subjects were subjected to artificial pigmentation (ultraviolet irradiation 3 times) by ultraviolet irradiation, and then subjected to a whitening measurement human test for a total of 6 weeks.

Using the test site as the inner part of both arms, use the products of Preparation Examples 1 to 4 and Comparative Preparation Examples 1 to 4 in the same amount twice a day each morning and evening, and affect the test results in addition to the paid products. The use of cosmetics in other formulations that may have been banned. At this time, the group using Production Examples 1 to 4 was classified as a test product (B), and the group using Comparative Production Examples 1 to 4 was classified as a control product (A).

Pigment using Chromameter C-300 (Minolta, Japan) at 0 weeks (ΔW0), 4 weeks after product application (ΔW4) and 6 weeks after product application (△ W6) Changes in L, a and b values of the deposited sites were measured, respectively.

L is the saturation factor, L is the brightness, a and b are the color factors, a is the green-to-red spectrum, and b is the blue-to-yellow spectrum. The parameter to indicate.

ITA (Individual Typological Angle) was obtained from L and b values (CHARDON A., CRETOIS I., HOURSEAU C., Skin color typology and suntanning pathways, 16 ^th IFSCC Congress, Oct. 8 ~) 10, NY, 1990).

The ITA value was calculated according to the following equation, and the high ITA value means that the skin is bright.

ITA = [Arc tan ((L * -50) / b *) × 180 / π

The results are shown in Tables 8 to 12 below.

In Table 12, when using a cosmetic containing the liquid crystals stabilized in the tranexamic acid, the skin whitening state is significantly improved compared to before use. Therefore, it can be seen that the cosmetic containing stanic triacid stabilized with liquid crystals according to the present invention is effective in whitening glandular lines of human skin.

(Test Example 4)

For Preparation Examples 1 to 4 and Comparative Preparation Examples 1 to 4, eight subjects were subjected to a wrinkle measurement human test for a total of six weeks.

Preparation Examples 1 to 4 and Comparative Preparation Examples 1 to 4 were used twice a day in the morning and evening around the left and right eyes, and in addition to the paid products, eye creams, whitening agents, and other anti-aging cosmetics that may affect the test results Banned any use of packs and massages. At this time, the group using Production Examples 1 to 4 was classified as a test product (B), and the group using Comparative Production Examples 1 to 4 was classified as a control product (A).

After 0 weeks (before application), 4 weeks, and 6 weeks, images were taken with a high-resolution digital camera (Camscope, Model DCS-105) for photographing wrinkles. By comparing the images of the wrinkled eyes, the degree of improvement of the wrinkles was evaluated by a global photodamage score based on Arch Dermatol vol. 137 (8): 1043-1051, 2001.

Global Photo Damage Score:

0: None 1: None / Weak

2: weak 3: weak / normal

4: moderate 5: moderate / severe

6: severe 7: very severe

The results are shown in Table 13 below.

In the above Table 13, when using a cosmetic containing liquid crystals stabilized in the tranexamic acid, the skin wrinkles were significantly improved compared to before use. Therefore, it can be seen that the cosmetic containing stanic triacid stabilized with liquid crystals according to the present invention is effective for improving wrinkles of human skin.

According to the present invention, by entrapping and stabilizing Tranexamic acid in the liquid crystal, it is very easy to penetrate into the skin, excellent in inhibiting melanin production and collagen biosynthesis, excellent anti-whitening effect and excellent anti-wrinkle effect, liquid crystal The stabilized tranexamic acid containing cosmetic composition is provided.

Claims (2)

A liquid crystals comprising tranexamic acid containing 0.01 to 20.0% by weight relative to the total weight of the cosmetic composition, characterized in that the liquid crystals stabilized Tranexamic acid-containing cosmetic composition. The method of claim 1, The tranexamic acid is characterized in that it is contained in 0.001 to 20% by weight relative to the tranexamic acid-containing liquid crystal, characterized in that the tranexamic acid-containing cosmetic composition stabilized.