KR102048713B1 - cosmetics containing boswellic acid - Google Patents

Abstract

The present invention is for skin whitening and containing any one selected from the group consisting of alpha-boswellic acid, beta-boswellic acid and / or mixtures thereof as an active ingredient. Or relates to a cosmetic composition for improving wrinkles, the skin whitening effect and wrinkle improvement effect is very excellent, do not occur side effects are excellent safety.

Description

Cosmetic composition containing boswellic acid {cosmetics containing boswellic acid}

The present invention relates to a cosmetic composition for skin whitening and / or anti-wrinkle comprising alpha-bosswellic acid and / or beta-bosswellic acid and / or mixtures thereof, and more particularly safely without side effects on the skin. It relates to a composition which can be used and has a melanin production inhibitory activity and / or collagenase activity inhibitory effect.

Skin is the largest tissue in the human body and plays an important role in protecting the interior of the skin from external stimuli as a primary barrier. These skins appear differently in color with age or with age, depending on the concentration and distribution of melanin inside the skin. Melanogenesis is a protective mechanism against melanocyte melanocytes (melanocytes) stimulation, such as ultraviolet rays, increases the melanogenesis activity, which is due to the transfer of large amounts of melanin to the keratinocytes accumulated in the skin epidermal layer The result is. Although melanin protects the skin, hyperpigmentation of the skin causes blemishes, freckles, darkening of the skin after skin inflammation, and senile pigment spots. It may also result. The melanin production process is made by tyrosinase, an amino acid called tyrosinase, which is transformed into dopa and dopaquinone, followed by a non-enzymatic oxidation reaction. It is known that spots, blotch, etc. are produced.

On the other hand, the skin of a person is deteriorated due to external chemical and physical stimulation, the skin's normal function is degraded, the aging phenomenon of the skin is promoted to cause skin damage. One of such skin aging is skin wrinkles. In general, skin wrinkles are known to be produced by a combination of various factors, such as skin moisture content, collagen content, and the ability to act against the external environment. Among these factors, the most influential effect on the formation of wrinkles is the expression and activity of collagenase, a collagen degrading enzyme that reduces collagen production and collagen content.

Various compositions have conventionally been used to inhibit whitening and wrinkle formation of the skin as described above. For example, various extracts extracted from L-ascorbic acid and derivatives thereof, hydroquinone, arbutin and licorice, and lettuce skin are used as skin whitening agents and anti-wrinkle agents. However, L-ascorbic acid is easily oxidized to cause irritation to the skin, and the cosmetics containing it cause discoloration and discoloration problems. The substances derived from plant extracts have a great difference in efficacy depending on the plant's origin, thus maintaining homogeneity of the product. It is difficult to do, and arbutin has the disadvantage of low effect.
[Preceding technical literature]
1.Dermatologic Therapy, 23, pp. S28-S32 (2010,01.19)
2.Planta Med., 76, pp. 555-560 (2009.11.16)

In order to solve the above problems, the present invention has no side effects on the skin, and excellent alpha-bosswellic acid, beta-bosswellic acid and / or mixtures thereof as an active ingredient having excellent skin whitening and antiwrinkle effect. It provides a cosmetic composition comprising.

The present invention provides a cosmetic composition selected from the group consisting of compounds represented by the following formulas (1) to (2) excellent in inhibiting melanin production and improving wrinkles.

Alpha-boswellic acid and beta-boswellic acid are components of the resin extract of olive and botanical Boswellia carterii Birdw. Pharmacological action of frankincense is known to have toxin removal, blood circulation and anti-inflammatory effects in the body, but there is a clear difference from the present invention.

The present invention provides a composition for skin whitening and / or anti-wrinkle containing any one or more from the group consisting of the compounds represented by Formulas 1 to 2 as an active ingredient.

The cosmetic composition of the present invention has an excellent whitening effect and wrinkle improvement effect, and there is little skin irritation to the human body, so the safety of the product is excellent, and thus it can be usefully used as a cosmetic composition for skin whitening and / or a cosmetic composition for wrinkle improvement. have.

Hereinafter, the present invention will be described in more detail.

The present invention is the alpha-boswellic acid of Formula 1 (α-boswellic acid, CAS No. 471-66-9), the beta-boswellic acid of Formula 2 (β-boswellic acid, CAS No. 631-69- It provides a skin whitening and / or wrinkle improvement cosmetic composition containing any one of 6) and / or a mixture thereof as an active ingredient.

Alpha-Boswellic acid, beta-Boswellic acid and / or mixtures thereof of the present invention have an excellent whitening effect by inhibiting melanin production, and have an excellent wrinkle improvement effect through inhibiting collagenase activity and promoting collagen synthesis. Therefore, the alpha-bosswellic acid, beta-bosswellic acid and / or mixtures thereof are useful as a cosmetic composition for skin whitening and wrinkle improvement. In addition, the cosmetic composition of the present invention is safe on human skin because it does not show a distinctive pattern in the skin accumulation stimulation test.

The content of alpha-bosswellic acid, beta-boswellic acid and / or mixtures thereof, which is included in the preparation of external skin ointments or cosmetics including alpha-bosswellic acid, beta-bosswellic acid and / or mixtures thereof. The dry weight is 0.00001 to 10.0% by weight, preferably 0.001 to 1.0% by weight based on the total amount of the silver composition. If the content of alpha-bosswellic acid, beta-bosswellic acid and / or mixtures thereof is less than 0.00001% by weight in dry weight based on the total amount of the composition, no distinct effect such as skin whitening could be expected, and if it exceeds 10.0% by weight There was no apparent increase in effect with increasing.

The components included in the cosmetic composition of the present invention include components conventionally used in cosmetic compositions in addition to alpha-bosswellic acid, beta-bosswellic acid and / or mixtures thereof as active ingredients, such as antioxidants, stabilizers, Conventional adjuvants such as solubilizers, vitamins, pigments and flavorings, and carriers.

The cosmetic composition of the present invention may be prepared in any formulation commonly prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing , Oils, powder foundations, emulsion foundations, wax foundations and sprays, and the like, but are not limited thereto. More specifically, it may be prepared in the form of a flexible lotion, astringent lotion, nutrition lotion, nutrition cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, pack, spray or powder.

When the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components. Can be.

When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, in particular in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizer or emulsifier is used as the carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 Fatty acid esters of, 3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan.

When the formulation of the present invention is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystals Soluble cellulose, aluminum metahydroxy, bentonite, agar or tracant and the like can be used.

When the formulation of the present invention is a surfactant-containing cleansing, the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide. Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.

Experimental Example 1

Inhibitory effect of melanin production at the cellular level

Alpha-Boswellic acid and Beta-Boswellic acid were added to the culture medium of B-16 mouse melanoma cells, respectively, and the whitening effect at the cellular level was tested as follows (Lotan R., Lotan D. Cancer Res. 40: 3345-3350, 1980).

Alpha-Boswellic acid and beta-Boswellic acid were added to the culture medium in the culture of B-16 melanoma cells at a final concentration of 1 μg / ml, 5 μg / ml and 50 μg / m, respectively, and then cultured for 3 days. Cells were treated with Trypsin, removed from the culture vessel, centrifuged, and melanin was extracted. Sodium hydroxide solution to the extraction of melanin (1N concentration) 1 ml and the reaction mixture was dissolved melanin boiled for about 10 minutes, the amount of the produced melanin by measuring the absorbance at 400 nanometers (nm) with a spectrophotometer unit cell allowance (10 ⁶ The experiment was carried out by a method showing the absorbance of the cell). The experiment was repeated three times and the average value was used to calculate the relative melanin production relative to the control group as inhibition rate (%), and the results are shown in Table 1 below.

sample Melanin production % Inhibition Control group (no addition) 0.047 ± 0.002 - Alpha-Boswellic Acid (final concentration 1 μg / ml) 0.031 ± 0.001 34 Alpha-Boswellic Acid (final concentration 5 μg / ml) 0.017 ± 0.001 64 Alpha-Boswellic Acid (final concentration 50 μg / ml) 0.008 ± 0.001 83 Beta-Boswellic Acid (final concentration 1 μg / ml) 0.036 ± 0.002 24 Beta-Boswellic Acid (final concentration 5 μg / ml) 0.022 ± 0.001 53 Beta-Boswellic Acid (final concentration 50 μg / ml) 0.014 ± 0.001 70 Hydroquinone (final concentration 1 μg / ml) 0.027 ± 0.002 43 Hydroquinone (final concentration 10 ㎍ / ml) Cell death

                                                      Iterations = 3

As shown in Table 1, alpha-Boswellic acid, beta-Boswellic acid and / or mixtures thereof are comparable to melanocyte production in cultured mouse melanoma cells as compared to hydroquinone, a previously known whitening substance. It can be seen that there is an inhibitory ability. In addition, hydroquinone has strong melanin production inhibitory ability at low concentrations, but can not be tested at 10 μg / ml or more due to severe cytotoxicity, but 50 μg / alpha-boswellic acid, beta-boswellic acid and / or mixtures thereof Since ml has a higher melanin production inhibitory effect than hydroquinone without showing cytotoxicity, this indicates that the present invention can be very useful for improving freckles and freckles and skin whitening.

Experimental Example 2

Wrinkle improvement effect test at the cellular level

The anti-wrinkle effect can usually be measured as collagen biosynthesis and collagenase degradation inhibitory effect and clinical trial in humans.

Human normal fibroblasts were seeded in 6-well microplates containing DMEM medium (2 × 10 ⁵ cells / well) and incubated at 37 ^° C. in a 5% CO ₂ incubator for 24 hours. After 24 hours, the medium was removed from each well, samples were treated by concentration and then incubated again for 24 hours. After 24 hours, cell media were collected to prepare samples.

Collagen synthesis amount was measured by using a collagen measurement kit (Procollagen type I C-peptide EIA kit (MK101), Takara, Kyoto, Japan) in procollagen (procollagen) type I C-peptide (type I C-peptide) in cell media. : Amount of PICP) was measured and analyzed.

An antibody against collagenase was used as a measure of the activity of collagenase that degrades collagen. Collagenase activity was determined using a type I collagenase assay kit (Amersham Biosciences, RPN2629), and the absorbance was measured by an ELISA reader. The measured standard values were expressed in the form of mean ± standard deviation and tested for significance by t-test using the SPSS / PC + program. The results are shown in Table 2 below.

sample Collagen Synthesis Growth Rate (%) Collagenase inhibition rate (%) Alpha-Boswellic Acid (final concentration 1 μg / ml) 21 18 Alpha-Boswellic Acid (final concentration 5 μg / ml) 43 35 Alpha-Boswellic Acid (final concentration 10 μg / ml) 79 55 Beta-Boswellic Acid (final concentration 1 μg / ml) 22 21 Beta-Boswellic Acid (final concentration 5 μg / ml) 37 31 Beta-Boswellic Acid (final concentration 10 μg / ml) 63 51

As shown in Table 2, alpha-bosswellic acid and beta-bosswellic acid increased collagen synthesis in a concentration-dependent manner, and also inhibited collagenase activity in a concentration-dependent manner. Therefore, it can be seen that alpha-bosswellic acid, beta-bosswellic acid, and / or mixtures thereof have anti-wrinkle effect.

Preparation Examples 1-2 and Comparative Example 1

Each component shown in Table 3 below was mixed in the ratio shown in Table 3 to prepare an external skin ointment.

Composition weight% Preparation Example 1 Preparation Example 2 Comparative Example 1 Alpha-Boswellic Acid
Beta-Boswellic Acid
Diethyl sebacate
Prepayment
Polyoxyethylene Oleyl Ether Phosphate
Sodium benzoate
vaseline 0.01
-
8
5
6
Quantity
Remaining amount * -
0.01
8
5
6
Quantity
Remaining amount * -
-
8
5
6
Quantity
Remaining amount *

*: Amount to be 100% by weight in total

Preparation Examples 3 to 4 and Comparative Example 2

Each component shown in Table 4 below was mixed in the ratio shown in Table 4 to prepare a nourishing cream.

Composition weight% Preparation Example 3 Preparation Example 4 Comparative Example 2 Alpha-Boswellic Acid
Beta-Boswellic Acid
Stearic acid
Cetanol
Fiji-20 sorbitan monostearate
Sorbitan monostearate
Mineral oil
Trioctanoate
Triethanolamine
Carbomer
glycerin
Propylene glycol
antiseptic
incense
Purified water 0.01
-
1.0
2.0
1.0
1.0
10.0
5.0
0.5
0.2
5.0
3.0
Quantity
Quantity
Remaining amount * -
0.01
1.0
2.0
1.0
1.0
10.0
5.0
0.5
0.2
5.0
3.0
Quantity
Quantity
Remaining amount * -
-
1.0
2.0
1.0
1.0
10.0
5.0
0.5
0.2
5.0
3.0
Quantity
Quantity
Remaining amount *

*: Amount to be 100% by weight in total

Preparation Examples 5 to 6 and Comparative Example 3

Each component shown in Table 5 was mixed in the same ratio as shown in Table 5 to prepare a flexible lotion.

Composition weight% Preparation Example 5 Preparation Example 6 Comparative Example 3 Alpha-Boswellic Acid
Beta-Boswellic Acid
ethanol
Polyoxyethylene Cured Castor Oil
Paraoxybenzoic Acid Methyl
glycerin
1,3-butylene glycol
incense
Pigment
Purified water 0.01
-
10.0
1.0
2
5.0
6.0
Quantity
Quantity
Remaining amount * -
0.01
10.0
1.0
2
5.0
6.0
Quantity
Quantity
Remaining amount * -
-
10.0
1.0
2
5.0
6.0
Quantity
Quantity
Remaining amount *

*: Amount to be 100% by weight in total

Preparation Examples 7 to 8 and Comparative Example 4

Each component shown in Table 6 was mixed in the same ratio as shown in Table 6 to prepare an essence.

Composition weight% Preparation Example 7 Preparation Example 8 Comparative Example 4 Alpha-Boswellic Acid
Beta-Boswellic Acid
Propylene glycol
glycerin
Sodium hyaluronate aqueous solution (1%)
ethanol
Polyoxyethylene Cured Castor Oil
Paraoxybenzoic Acid Methyl
Carbomer
Triethanolamine
incense
Purified water 0.01
-
10.0
10.0
5.0
5.0
1.0
0.1
0.3
0.4
Quantity
Remaining amount * -
0.01
10.0
10.0
5.0
5.0
1.0
0.1
0.3
0.4
Quantity
Remaining amount * -
-
10.0
10.0
15.0
5.0
1.0
0.1
0.3
0.4
Quantity
Remaining amount *

*: Amount to be 100% by weight in total

Preparation Examples 9 to 10 and Comparative Example 5

Each component shown in Table 7 below was mixed in the same ratio as shown in Table 7 to prepare a pack.

Composition weight% Preparation Example 9 Preparation Example 10 Comparative Example 5 Alpha-Boswellic Acid
Beta-Boswellic Acid
glycerin
Propylene glycol
Polyvinyl alcohol
ethanol
Polyoxyethylene Cured Castor Oil
Polyoxyethylene Oleethyl
Paraoxybenzoic Acid Methyl
incense
Pigment
Purified water 0.01
-
5.0
4.0
15.0
8.0
1.0
1.0
0.2
Quantity
Quantity
Remaining amount * -
0.01
5.0
4.0
15.0
8.0
1.0
1.0
0.2
Quantity
Quantity
Remaining amount * -
-
5.0
4.0
15.0
8.0
1.0
1.0
0.2
Quantity
Quantity
Remaining amount *

*: Amount to be 100% by weight in total

Preparation Examples 11 to 12 and Comparative Example 6

Each component shown in Table 8 was mixed in the same ratio as shown in Table 8 to prepare a nourishing lotion.

Composition weight% Preparation Example 11 Preparation Example 12 Comparative Example 6 Alpha-Boswellic Acid
Beta-Boswellic Acid
Polyoxyethylene Cured Castor Oil
Paraoxybenzoic Acid Methyl
glycerin
1,3-butylene glycol
Carbomer
Triethanolamine
Propylene glycol
ethanol
Carboxy Vinyl Polymer
Pigment
incense
Purified water 0.01
-
1.0
Quantity
6.0
5.0
0.2
0.3
5.0
2
One
Quantity
Quantity
Remaining amount * -
0.01
1.0
Quantity
6.0
5.0
0.2
0.3
5.0
2
One
Quantity
Quantity
Remaining amount * -
-
1.0
Quantity
6.0
5.0
0.2
0.3
5.0
3.2
0.1
Quantity
Quantity
Remaining amount *

*: Amount to be 100% by weight in total

Experimental Example 3

Whitening effect test in clinical

Forty healthy men and women were selected and covered with aluminum foil in two rows of six holes with a diameter of 7 mm in the lower part of both arms and 60 mJ with a ORIEL Solar Simulator 1000W at a distance of 10 cm from the arm. The amount of light of / cm 2 was investigated. Sample containing no alpha-boswellic acid or beta-boswellic acid prepared according to Preparation Examples 1-12 and Comparative Examples 1-6, and containing no bases, twice a day from 3 days before irradiation to 3 weeks after irradiation. Was applied to the same line in pairs. Here, in the case of the pack formulations of Preparation Examples 9 to 10 and Comparative Example 5 after the application was removed after 15 minutes. For each of the above, the pigmentation degree of the preparation example and the comparative example was visually determined, and the results are shown in Table 9 below.

Experimental substance Distinct Effects (persons) Effective (persons) No difference (persons) Preparation Example 1 7 7 6 Preparation Example 2 6 7 7 Preparation Example 3 2 10 8 Preparation Example 4 2 9 9 Preparation Example 5 One 9 10 Preparation Example 6 2 9 9 Preparation Example 7 2 9 9 Preparation Example 8 2 10 8 Preparation Example 9 3 8 9 Preparation Example 10 2 9 9 Preparation Example 11 3 9 8 Preparation Example 12 3 8 9

As shown in Table 9, the whitening ointment and cosmetics prepared according to the preparations 1-12 showed a whitening effect on at least 10 or more of 20 subjects, and also showed no side effects in the skin, and thus was safe. It can be seen that the skin whitening agent has an excellent effect on improving blemishes and freckles.

Experimental Example 4

Wrinkle improvement effect test in clinical

Evaluation of the wrinkle improvement effect was performed as follows. Sixty 30 to 40 year old women were randomly divided into three groups, and the creams of Preparations 3 to 4 and Comparative Example 2 were washed twice every morning, and then the appropriate amount was corrected continuously for 2 months around the eyes. The wrinkle improvement effect of each subject was evaluated through visual observation. The experimental results are shown in Table 10 below.

Experimental substance Distinct Effects (persons) Effective (persons) No difference (persons) Preparation Example 3 9 7 4 Preparation Example 4 8 8 4 Comparative Example 2 - 6 14

As shown in Table 10, the cream prepared according to 3 to 4 in the preparation showed a wrinkle improvement effect for 16 out of 20 subjects, and also did not show any side effects in the skin, thus having a safe and excellent effect. It can be seen that it is an anti-wrinkle agent.

Claims (4)

A composition for skin whitening comprising an alpha-bosswellic acid of Formula 1, beta-bosswellic acid of Formula 2, or a mixture thereof

delete The method of claim 1,
An alpha-bosswellic acid, beta-bosswellic acid, or a mixture thereof of Formula 1 comprising 0.00001 to 10.0 wt% based on the total amount of the composition. According to claim 1, wherein the composition is a skin, lotion, cream, foundation, essence, gel, pack, product cleansing and ointment is a composition for skin whitening, characterized in that formed in any one.