KR101858095B1 - Cosmetic composition comprising Curcumae Longae Rhizoma extract comprising curcumin as an active ingredient for skin lightening, reducing wrinkle formation, and alleviating pruritus - Google Patents

Abstract

The present invention relates to an effective, non-adverse and safe topical cosmetic composition comprising a turmeric extract containing curcumin, which inhibits melanin production of skin induced by ultraviolet light or inflammation, inhibits wrinkle formation, alleviates pruritus To a cosmetic composition having excellent efficacy.

Description

[0001] The present invention relates to a cosmetic composition for skin whitening, inhibition of wrinkle formation, and alleviation of pruritus containing an extract of turmeric containing curcumin as an active ingredient, and a cosmetic composition for alleviating pruritus }

The present invention relates to an effective, non-adverse and safe topical cosmetic composition comprising a turmeric extract containing curcumin, which inhibits melanin production of skin induced by ultraviolet light or inflammation, inhibits wrinkle formation, alleviates pruritus The present invention relates to a cosmetic composition which is excellent in the effect of making a cosmetic composition.

Human skin color is derived from a complex series of cellular reactions taking place within a specific population of cells called melanocytes. Melanin-producing cells are located in the lower part of the epidermis, and its function is to synthesize melanin, a pigment that protects the body from harmful effects caused by ultraviolet irradiation. The darkness of the color observed in the skin is proportional to the amount of melanin synthesized by the melanin-producing cells. For skin whitening, aging and black spot removal, it is desirable to reduce or inhibit melanin production or to reduce hyperactive melanin producing cells.

On the other hand, the components constituting the skin dermis include cells such as fibroblasts and endothelial cells, and substances constituting an extracellular matrix such as collagen, elastin and fibronectin. When they are abnormally generated or decomposed It affects the structure of the entire skin, wrinkles on the skin, and skin elasticity is lowered. Among them, collagen, which is the most remarkable component in wrinkle generation, is decomposed by aging and photoaging by ultraviolet irradiation, which is the most important factor in generating wrinkles on the skin and reducing skin elasticity.

In addition, many modern people suffer from acute, intermittent, or persistent pruritus due to UV radiation, stress, anxiety, idiopathic, allergic, metabolic, infectious, and the like.

Various kinds of cosmetics have been developed for the reduction of skin melanin production, suppression of wrinkle formation, and alleviation of pruritus. Among them, cosmetics derived from natural products are popular among general consumers. This is because cosmetics derived from natural products have few side effects, are generally mild in function, are persistent, have high biodegradability, and are environmentally friendly. For these reasons, developed countries such as the US and Japan are spurring research into the development of cosmetics derived from natural products .

Based on the development and discovery of inhibitors of matrix metalloproteinase (MMP) activity to inhibit wrinkle formation and whitening products based on the development and discovery of a tyrosinase inhibitor for the inhibition of melanin production, One of the most active research is aging cosmetics. Many companies are delaying the release of newly developed ingredients because they are waiting for new active ingredients that are more effective.

Among the new active ingredients, polyphenol substances such as caffeic acid phenethyl ester (CAPE) have been clinically proven to have antiinflammatory and melanogenesis inhibitory effects. Previous studies have reported that these polyphenolic compounds affect transcription factors such as NF-κB and T-cell activation factors (NFAT) or various enzyme proteins.

On the other hand, the mechanism of calcium ion channel regulation through the calcium ion channel in melanocytes has been relatively recent and has not yet been extensively researched. However, Nadine et al. UVA Phototransduction Drives Early Melanin Synthesis in Human Melanocytes. 2011, Current biology, IF = 9.494], it has been shown that UVA-induced melanogenesis is accompanied by an increase in intracellular calcium ion concentration by rhodopsin initially; Bellono et al. UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes. In 2013, Proc Natl Acad Sci U S A, IF = 9,737, revealed that the increase of initial calcium ion concentration by ultraviolet light in melanocytes was caused by TRPA-1, a cation channel; Stanisz et al., ORAI1 Ca2 + channels control endothelin-1-induced mitogenesis and melanogenesis in primary human melanocytes. 2012, J Invest Dermatol.] Has shown that ET-1 produced from keratinocytes by ultraviolet light activates the ORAI-1 calcium ion channel and increases calcium ion concentration in melanocytes. All of the documents listed above are listed in the upper journals of the field of dermatology, and the possibility of developing the related technology is very promising in the future.

The present invention is based on the finding that curcumin contained in the extract of turmeric extract is useful as a skin melanin-producing agent, which is effective for skin whitening and pruritus, , Reduction of wrinkle formation, and alleviation of pruritus. The present invention has been completed based on this finding.

It is an object of the present invention to provide a cosmetic composition which is capable of reducing melanin production, reducing wrinkle formation, and alleviating pruritus, while reducing the risk of side effects such as skin troubles by using a naturally occurring substance, curcumin.

In order to achieve the above object, the present invention provides a cosmetic composition comprising a turmeric extract containing curcumin as an active ingredient.

The cosmetic composition comprising an extract of turmeric containing curcumin of the present invention as an active ingredient has no irritation to the skin and is excellent in skin whitening, reduction of wrinkle formation, and alleviation of pruritus through reduction of skin melanin production induced by ultraviolet rays or inflammation .

Until now, pigmentation and wrinkle formation due to ultraviolet irradiation have been caused by the same cause. However, since different enzymes are used, different drugs have been used and different drugs have been used to alleviate pruritus. However, The effect can be shown at the same time.

FIG. 1 shows the expression level of TRPV-1 according to age and the ultraviolet-induced wrinkle fish pathway.
Figure 2 shows the melanogenesis mechanism of melanocytes.
Figure 3 shows the activation mechanism of the ion channel associated with calcium ion concentration regulation.
4 shows a method for producing a fraction using a herbal medicine material.
Figure 5 illustrates one embodiment of a patch clamp.
Fig. 6 shows the calcium signal inhibitory effect of curcumin and the inhibitory effect on each ion channel in human T-cells.
Fig. 7 shows the effect of curcumin on inhibition of melanin formation compared to kojic acid.

Various embodiments and / or aspects are now described with reference to the drawings. In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of one or more aspects. However, it will also be appreciated by those of ordinary skill in the art that such aspect (s) may be practiced without these specific details. The following description and the annexed drawings set forth in detail certain illustrative aspects of one or more aspects. It is to be understood, however, that such aspects are illustrative and that some of the various ways of practicing various aspects of the principles of various aspects may be utilized, and that the description set forth is intended to include all such aspects and their equivalents.

In addition, the term "or" is intended to mean " exclusive or " That is, it is intended to mean one of the natural inclusive substitutions "X uses A or B ", unless otherwise specified or unclear in context. That is, X uses A; X uses B; Or when X uses both A and B, "X uses A or B" can be applied to either of these cases. It should also be understood that the term "and / or" as used herein refers to and includes all possible combinations of one or more of the listed related items.

It is also to be understood that the term " comprises "and / or" comprising " means that the feature and / or component is present, but does not exclude the presence or addition of one or more other features, components and / It should be understood that it does not. Also, unless the context clearly dictates otherwise or to the contrary, the singular forms in this specification and claims should generally be construed to mean "one or more. &Quot;

Further, the term "skin" includes, but is not limited to, mammalian face, neck, chest, back, arms, armpits, hands, legs and scalp.

Hereinafter, the present invention will be described in detail.

The cosmetic composition according to the present invention contains a turmeric extract containing curcumin as an active ingredient.

In one aspect of the present invention, the purity of the curcumin is 90% to 98%.

In one aspect of the present invention, the purity of the curcumin is 95%.

Further, one aspect of the present invention includes 0.0001 to 1% by weight of the curcumin based on the total weight of the composition.

Further, one aspect of the present invention includes 0.00033 to 1% by weight of the curcumin based on the total weight of the composition.

Further, one aspect of the present invention includes 0.001 to 0.002% by weight of the curcumin based on the total weight of the composition.

In another aspect of the present invention, the curcumin is included in an amount of 0.02% by weight based on the total weight of the composition.

In addition, one aspect of the present invention has the effect of reducing melanin production.

Further, one aspect of the present invention has a wrinkle reduction effect.

Further, one aspect of the present invention has an effect of alleviating pruritus.

In addition, one aspect of the present invention has two or more efficacies selected from the group consisting of reduced melanogenesis, decreased wrinkle formation, and alleviation of pruritus.

One aspect of the invention is also a topically applied formulation.

One aspect of the invention is also characterized in that the topically applied formulation is an oil, a skin, an essence, a serum, a mask pack, a lotion, a cream, or a gel.

Animal cells have a membrane voltage of about -50 to -90 mV by the flow of ions, that is, the flow of ion currents inside and outside the cells. Herein, a protein that makes ions pass through the inside and outside of a cell is called an ion channel, and the ion channel is responsible for maintaining the physiological difference between the inside and outside of the cell and the cell layer It also plays an important role. In other words, the ion channel is the most basic functional unit for controlling and controlling the flow of the cell current. In fact, due to the action of the ion channel, a variety of physiological phenomena such as changes in brain waves and heartbeat, electrolyte secretion, etc. appear.

On the other hand, the most important cause of aging is the breakdown of collagen, which accounts for about 80% of the dry weight of the skin. Decrease of skin collagen content due to aging induces skin wrinkles. This phenomenon occurs in both extrinsic and endogenous aging. It is closely related to the development of pathways. As shown in FIG. 1, the expression levels of TRPV-1, a calcium permeable ion channel in skin tissue obtained from a young patient in the twenties and skin tissues obtained from patients over 70 years old, -1 is more expressed. The TRPV-1 is a typical calcium ion pathway activated by ultraviolet light and heat. When expressed, the intracellular calcium ion concentration is increased, thereby activating MMP-1, collagen is broken, and skin wrinkles are induced.

Skin pigmentation is also associated with the expression of calcium-permeable ion channels. Endothelin-1 (ET-1) is secreted from keratinocytes when exposed to ultraviolet light, which binds to ET-B receptors in peripheral melanocytes. When endothelin-1 binds to the ET-B receptor, a number of calcium-permeable ion channels such as ORAI-1 and TRPA-1 in melanocytes act to increase the concentration of calcium ions in the melanocytes. The increase causes cell proliferation and melanin production. ET-1 also reduces DNA damage by ultraviolet light in melanocytes and prevents apoptosis. FIG. 2 is a schematic diagram of a melanin-producing mechanism in melanocytes. When ultraviolet rays are irradiated to skin, rhodopsin present in melanocytes recognizes it and causes phototransduction. In the short term, TRPA-1 is activated In the long term, it induces ET-1 secretion of keratinocytes, activating melanocyte ET-1 receptors, resulting in ORAI-1 activity, resulting in continuous melanin production.

The present invention relates to the regulation of the activity of ion channels associated with the regulation of calcium ion concentration in melanin cells during the melanin production step and is generally a different approach from the previous studies which attempted to regulate the activity of tyrosinase or melanogenesis, . In this regard, the activation mechanism of the ion channel associated with the regulation of calcium ion concentration commonly occurring in skin photoaging and skin pigment deposition is illustrated in FIG.

Calcium ion channels that regulate melanocyte proliferation and melanin production include, for example, ORAI-1, STIM-2, and TRPA-1.

ORAI-1 and STIM-2: melanocytes have both store-operated calcium ion channels such as ORAI-1 to -3 and STIM-1 and -2 that can regulate their activity , And it is known that ORAI-1 and STIM-2 are most expressed. When the ORAI-1 ion channel gene is knocked down by ET-1, intracellular calcium ion concentration by ET-1 is decreased and cell proliferation and melanin production do not occur well.

TRPA-1: When melanocytes are exposed to ultraviolet light, melanocytes directly increase intracellular calcium ion concentration without being affected by keratinocytes. It is known that TRPA-1 acts in this process.

As we have seen, the increase in calcium ion concentration in melanocytes by various ion transport channels and ion channel regulating proteins is a common phenomenon occurring in both skin photoaging and melanin production. Specifically, they are specifically associated with TRPV-1 and ORAI- It is characterized by passing through a common passage. Accordingly, there is a need for the development of cosmetic compositions comprising an active ingredient that can reduce melanin production while delaying or alleviating exogenous aging by modulating these. In view of the above, curcumin, which is a plant-derived natural substance capable of inhibiting TRPV-1, ORAI-1 and / or intracellular calcium increase of the present invention, is excellent in reducing skin melanin production and reducing wrinkle formation. In addition, curcumin has surprisingly been found to have antitussive efficacy, and thus it can be used as an effective ingredient of epoch-making functional cosmetics having effects of alleviation of pruritus, in addition to reduction of skin melanin production and wrinkle formation.

The curcumin contained in the cosmetic composition of the present invention preferably has a purity of 90% to 98%, more preferably 93% to 96%, and most preferably 95%.

The curcumin contained in the cosmetic composition of the present invention is preferably 0.0001 to 1 wt%, more preferably 0.00033 to 1 wt%, 0.001 to 0.002 wt%, or 0.02 wt%, based on the total weight of the composition. The amount of curcumin can be used in an appropriate range depending on the formulation of the composition and the desired effect.

One effect of the cosmetic composition of the present invention is reduced melanin production, which is used in a broad sense and may mean, but is not limited to, removal of spots, freckles, spots, aging or black spots, prevention of pigmentation, or skin whitening .

The reduction in wrinkle formation, an effect of the cosmetic composition of the present invention, is used in a broad sense and may mean reduced wrinkles, reduced deep wrinkles, or improved skin elasticity, but is not limited thereto.

In the treatment of pruritus, an efficacy of the cosmetic composition of the present invention, pruritus is used in a broad sense and refers to all types of itchy and stinging sensations of acute intermittency and persistence which can be generally described by being restricted to the local area. The pruritus may be, but is not limited to, by UV irradiation, stress, anxiety, idiopathic, allergic, metabolic, infectious, drug-induced, liver, kidney disease or by cancer.

The formulation of the cosmetic composition of the present invention is not particularly limited and can be made into various formulations that can be widely used in the cosmetics field, and these formulations can be prepared by conventional methods known in the art. The topical application form is preferably an oil, a skin, an essence, a serum, a mask pack, a lotion, a cream, or a gel, but is not limited thereto .

The cosmetic compositions of the present invention can be used in all mammals, including humans.

The cosmetic compositions of the present invention may comprise cosmetically acceptable excipients. Such excipients are known to those skilled in the art and such excipients may include other forms capable of delivering the active ingredient to the skin layer in oils, skins, essences, serums, mask packs, lotions, creams,

The cosmetic composition of the present invention may contain other cosmetically or therapeutically acceptable carriers containing other solvents, moisturizers, wetting agents, oils, emulsifiers, thickeners, diluents, surface activators, flavors, preservatives, antioxidants, vitamins or minerals But the present invention is not limited thereto.

The cosmetic composition of the present invention can be used in combination with other active ingredients for the reduction of melanin production, reduction of wrinkle formation, and / or alleviation of pruritus, so that each of the detailed effects can be designed step by step, It is possible to reinforce the design according to the synergistic effect.

< Example >

The following are examples and comparative examples for examining the preparation examples and effects of the cosmetic composition according to the present invention. These embodiments are only for illustrating the present invention, and the scope of protection of the present invention is not limited by these embodiments.

Example  1: plant extract and Fraction  Produce

The herbal medicine material was dried well and powdered and then extracted with heating with 70% ethanol for 5 hours to prepare an extract. The extract was made into a solvent fraction having a different polarity of the solvent, This strong fraction was subjected to component separation. The extract, fraction and component separation method using a specific herbal medicine material are shown in Fig.

Example  2: skin cell calcium ion channel ( TRPV -One, ORAI -1, and STIM -1) expression in human cell lines

The patch clamp technique was used to examine how the activity of each calcium ion channel was controlled according to the fractions and components of the herbal medicine material according to Example 1. One embodiment of the patch clamp technique is shown in FIG.

Human ORAI-1 and TRPV-1 genes involved in skin barrier formation were introduced into HEK293T cell lines using transient transfection techniques. Since it is not possible to distinguish the calcium ion pathway in which cells are expressed in the naked eye, a green fluorescence protein (GFP) is expressed together, and a patch clamp experiment is performed only on cells showing fluorescence as shown in FIG. The membrane voltage clamp method for HEK293 cells in which the calcium ion channel protein was overexpressed was a whole cell patch clamp method.

Example  3: Cell ion current measurement using patch clamp

In order to quickly determine the inhibition of TRPV-1 and ORAI-1 by the active and active ingredients, HEK293 cells overexpressing TRPV-1 and ORAI-1 were subjected to a cell clamping method using a patch clamp.

The glass electrode used was a resistance of 2 to 4 MW when the cell membrane voltage clamp method was performed, a resistance of 1.2 MW or less when the cell attachment patch clamp was performed inside out. The overall signal from the patch clamp amplifier (Axopatch 1-D, Axon instruments, USA) was digitized and stored via Axoscope 9.0 (Axon instruments, USA). Digital-to-analog converter (Digidata-1322A) equipped with a personal computer with an operating clock of 3.2GHz and a pClamp software v9.2 to record and store the current response at a fixed voltage and excitation voltage, : Axon instruments, USA). The results obtained from the membrane voltage clamp test were analyzed and processed using Clampfit v9.2 origin (Microcal software, USA). The intracellular and extracellular ionic compositions for investigating the activity of TRPV-1 and TRPA-1 were as follows.

Example  4: Tyrosinase  Suppressive effect black

The mixture of mushroom tyrosinase (EC 1.14.18.1), the plant extract according to Example 1, phosphate buffer solution (pH 6.5) and tyrosine was incubated at 37 ° C for 12 minutes and then diluted with a microplate reader at 490 nm The absorbance was measured. The efficacy of the extracts was calculated as% inhibition for the control.

Example  5: Melanoma  Cell culture

B16 murine melanoma cells were cultured in DMEM medium supplemented with 10% fetal bovine serum and penicillin / streptomycin at 5% CO ₂ and 37 ° C. Then, trypsin and EDTA A confluent monolayer of melanocytes was obtained using the mixed solution.

Example  6: Measurement of melanin content

In the medium containing the plant extract according to Example 1, B16 mouse melanoma cells cultured according to Example 5 were washed with PBS and the amount of melanin contained therein was calculated by measuring the absorbance at 405 nm. At this time, arbutin was used as a positive control substance.

Example  7: Elastase  Measure inhibitory activity

The enzyme reaction was carried out by adding 1300 μl of a substrate solution in which N-succinyl-Ala-Ala-Ala-p-nitroanilide (1 mM) was added to Tris-Cl (0.12M, pH 8.0) and 10 mg of a sample in 1 ml of DMSO 7.5 μl of the dissolved solution was used. Kojic acid was used in 7.5 μl of 200 μg / ml solution. Then, 92.5 .mu.l of Tris-Cl (0.12M, pH 8.0) solution was added and then pre-incubated for 10 minutes. Then, 100 .mu.l of enzyme solution (0.0375 U / ml of elastase) Incubation was carried out for a minute and absorbance was measured at 410 nm.

Example  8: Using patch clamp technology Curcumin  Measurement of calcium ion channel regulation

On the basis of Examples 1 to 7, TRPV-1 and ORAI-1, which are calcium ion channels which play an important role in blackening and wrinkle formation by ultraviolet rays, were examined. Curcumin contained in the turmeric extract was mixed with the above- Experiments were conducted to see if the activity of the channel could be effectively inhibited. As a result, it was found that calcium signaling in human T-cells activated by administration of anti-CD3 antibody (5 ug / ml) was completely blocked by curcumin.

Specifically, when the curcumin was pretreated and given anti-CD3 stimulation, there was little increase in intracellular calcium ion concentration (FIG. 6A). The increased calcium secretion-activated channel (CRAC) was shown to be inhibited by 70% or more by 1 mM curcumin, which means that the calcium-secretion-active channel inhibition effect by curcumin is very high (FIG. 6B). Curcumin also showed inhibitory effects on the K ⁺ ion channel (K _Ca ) and the membrane voltage-dependent K ⁺ ion channel activated by intracellular calcium ions (FIGS. 6C and 6D).

As a result, the curcumin blocking effect on the calcium ion channel (ORAI-1) and the potassium ion channel was very effective and was superior to other polyphenol materials known to have antioxidant effects.

In addition, when melanoma cell line B16F10 cells were treated with IBMX to induce melanin production, and then the tyrosinase inhibitors kojic acid and curcumin were treated at different concentrations to inhibit melanin production, Production inhibition effect was more excellent. In particular, curcumin exhibited an excellent inhibitory effect on melanin production even at a concentration 10 times lower than that of kojic acid (Fig. 7). In FIG. 7, "dm" and "dm ib" are the control group, "dm" is a standard before melanin before IBMX treatment, and "dm ib" is a standard after melanin is generated after IBMX treatment.

In other words, curcumin strongly inhibited the ORAI-1 ion channel at a low concentration, and it was found that it strongly inhibits melanin production and wrinkle formation, which are the most important in skin whitening.

Example  9: Measures to relieve pruritus

Mosquitoes, or pests, and after 100 minutes of rubbing at least twice a minute with severe itching within 15 minutes, a total of 10 subjects were randomly assigned to 10 groups to measure the mitigation effect of pruritus Respectively. As a composition according to the present invention, a composition prepared by stirring 0.02% by weight of curcumin (purity: 95%) in vegetable oil was used, and as a comparative agent, a commercially available product (system solution: Donga Pharmaceutical Co., Ltd.) was used . One of the scratching areas on each subject was applied with 0.5 ml of the composition according to the invention and 0.5 ml of the comparison formulation on the other. After 1 minute, 10 minutes, and 30 minutes after application, subjects were asked whether they had itching. The number of people who experienced itching is shown in Table 1 below. Here, itching was defined as scratching two or more times in an itchy area.

As can be seen from Table 1, when the oil composition containing 0.02% by weight of curcumin (95% purity) according to the present invention is applied, the effect of alleviating pruritus is excellent, which is dramatically increased with time.

As a result, it can be seen that the cosmetic composition of the present invention can reduce user's skin melanin production and wrinkle formation, and at the same time can alleviate pruritus, thereby increasing the convenience of the user.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. And various changes can be made without departing from the scope of the invention.

The description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features presented herein.

Claims (13)

A cosmetic composition comprising a turmeric extract containing curcumin as an active ingredient,
The curcumin may be:
Regulating the activity of the calcium ion channel in the skin tissue, said calcium ion channel comprising TRPV-1 or ORAI-1; And
Which controls the activity of the ion channel associated with the regulation of calcium ion concentration in the melanin cells during the melanin production step,
A cosmetic composition. The cosmetic composition according to claim 1, wherein the purity of the curcumin is 90% to 98%. The cosmetic composition according to claim 2, wherein the purity of the curcumin is 95%. The cosmetic composition according to any one of claims 1 to 3, wherein the curcumin is present in an amount of 0.0001 to 1% by weight based on the total weight of the composition. 4. The cosmetic composition according to any one of claims 1 to 3, wherein the curcumin is present in an amount of 0.00033 to 1% by weight based on the total weight of the composition. 4. The cosmetic composition according to any one of claims 1 to 3, wherein the curcumin is present in an amount of 0.001 to 0.002% by weight based on the total weight of the composition. 4. The cosmetic composition according to any one of claims 1 to 3, wherein the curcumin is present in an amount of 0.02% by weight based on the total weight of the composition. The cosmetic composition according to any one of claims 1 to 3, which has a melanin production-reducing effect. The cosmetic composition according to any one of claims 1 to 3, which has a wrinkle reduction effect. The cosmetic composition according to any one of claims 1 to 3, which has an alleviation effect on pruritus. 4. The cosmetic composition according to any one of claims 1 to 3, having at least two effects selected from the group consisting of reduction of melanin production, reduction of wrinkle formation, and alleviation of pruritus. 4. The cosmetic composition according to any one of claims 1 to 3, which is a topical application form. 13. The cosmetic composition of claim 12, wherein the topically applied formulation is an oil, a skin, an essence, a serum, a mask pack, a lotion, a cream, or a gel.

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