KR20150009339A - Composition for skin whitening - Google Patents

Abstract

The composition for whitening according to the present invention contains piperlongmumin, so that it is possible to provide a whitening effect on an excellent skin even in a small amount. In addition, Piper Longin is a natural ingredient, it can be used only a small amount, so it is safe to the skin.
Accordingly, the composition according to the present invention can be used as an external preparation for skin, and can be used in various applications in cosmetic compositions, medicinal compositions and food compositions.

Description

[Composition for skin whitening]

Described herein is a novel use of Piper longinum for skin.

One of the most important criteria of beauty today is the need to solve the problems of cosmetic and cosmetic treatment of hyperpigmentation in order to have clean, white, clean skin.

The most important factor determining the skin color of a human is melanin produced by various enzymes such as tyrosinase in melanocytes in the human body. When melanin is generated more than necessary, hyperalgesia such as spots, freckles and spots Resulting in poor cosmetic results. Melanin, which is produced by stress stimuli inside and outside of the skin, does not disappear until the stress is eliminated but it is excreted through skin keratinization.

Therefore, studies for suppressing the production of melanin are under way, and substances having inhibitory activity against ascorbic acid, kojic acid, arbutin, hydroquinone, glutathione, derivatives thereof, or tyrosinase are added to cosmetics or medicines Has been used. However, their use is limited due to their inadequate whitening effect and skin safety problems.

Lakshmi Raj et al., Selective killing of cancer cells by a small molecule targeting stress response to ROS, Nature 475, 231-234 (2011 Jul 13) Beena Joy et al., Comparison and bioevaluation of Piper longum fruit extracts, J. Chem. Pharm. Res., 2010, 2 (4): 612-622

In order to solve the above problems, it is an object of the present invention to provide a composition capable of exhibiting excellent whitening effect on skin with only a small amount.

In order to solve the above-mentioned problems, an embodiment of the present invention provides a whitening composition comprising Piperlongumine as an active ingredient.

More specifically, one embodiment of the present invention provides a whitening composition comprising from 0.001 to 20% by weight, based on the total weight of the composition, of piper long isomer.

The composition for whitening according to the present invention contains piperlongmumin, so that it is possible to provide a whitening effect on an excellent skin even in a small amount. In addition, Piper Longin is a natural ingredient, it can be used only a small amount, it is safe because it does not stimulate the skin.

Accordingly, the composition according to the present invention can be used as an external preparation for skin, and can be variously applied to cosmetic compositions, medicinal compositions and food compositions.

FIG. 1 is a graph showing the results of a comparative experiment of melanin production inhibitory effects of Piperlongumine and α-MSH in malignant melanoma cells and Kojic acid and Arbutin in positive control groups.
FIG. 2 is a graph showing the results of a comparative experiment of melanin production inhibitory effects of Piper longum in normal cells, arbutin as a positive control, and Piper longum extract as a comparative example.
Fig. 3 is a graph showing the results of a comparative experiment of melanin production inhibitory effects of Piperlongmin in normal cells and Piperlonguminine in a comparative example.

Hereinafter, the present invention will be described in detail.

One embodiment of the present invention provides a whitening composition comprising Piperlongumine as an active ingredient.

Piperlongumine (PL) is a mixture of Piper longum ) is one of the constituents of the fruit, and the structure thereof is as follows.

[Chemical Formula 1]

Wherein R 1 to R 12 are each hydrogen or C ₁ -C ₆ alkyl, C ₁ -C ₆ alkenyl or C ₁ -C ₆ alkynyl. Specifically, in one embodiment according to the present invention, R1 to R9 and R13 are hydrogen and R10 to R12 are methyl.

More specifically, the IUPAC name of Piper longum according to one embodiment of the present invention is 1 - [(2E) -3- (3,4,5-trimethoxyphenyl) prop-2- 2-enoyl] -5,6-dihydropyridin-2 (1H) -one) (1 - [(2E) -3- (3,4,5-Trimethoxyphenyl) prop- And the CAS number is 2006-09-09-4.

Recently, it has been reported that Piper longingmin induces the activity of cancer-killing enzymes to reduce the size of cancer cells. At this time, it has been reported that the anticancer component of Piper longingmin selectively kills cancer cells and does not affect other cells (Lakshmi Raj et al. , Selective killing of cancer cells by a small molecule targeting stress response to ROS, Nature 475, 231-234, 2011 Jul 13), no study has been reported on the use of Piper longinmin for skin whitening. The content of the above document on the Piper longin component is incorporated herein by reference in its entirety.

As a result of the study, the inventors of the present invention have found that the above-mentioned Piperlong canin inhibits the production of melanin by inhibiting the production of tyrosinase in melanocytes in the human body. Thus, the present invention provides a composition having a whitening application . Accordingly, the composition according to one embodiment of the present invention includes piper longummin to improve skin color, prevent or alleviate hyperpigmentation, and exhibit excellent whitening effect.

On the other hand, a known pepper compound in addition to Piper longummin as an active ingredient of the present invention is Piperlonguminine, and its structure is as follows.

(2)

The IUPAC name of Piper longingminin is 5-benzo [1,3-dioxo] -5-yl-en- (2-methylpropyl) penta-2,4-dienamide (5-Benzo- [ -5-yl-N- (2-Methylpropyl) Penta-2,4-Dienamide. The above-mentioned Piper long gumicin is contained in a pepper extract and is known to have a whitening effect as in the case of Piper longum. However, whitening efficacy is lower than that of arbutin and kojic acid, which are included in the existing whitening cosmetics, There is a disadvantage that a large amount must be included. Therefore, there is a problem that it is difficult to use the cosmetic composition or the pharmaceutical composition substantially.

However, the effective ingredient of the present invention, Piper longumin, can provide a whitening effect on a good skin even with a small amount.

Accordingly, one embodiment of the present invention provides a whitening composition, which comprises 0.001 to 20% by weight of Piper longinmin based on the total weight of the composition. The composition may contain 0.01 to 15% by weight, more specifically 0.1 to 10% by weight, of piperlongmium. If it is contained in an amount of less than 0.001% by weight, the present invention is not suitable for exhibiting an intended skin whitening effect, and if it is contained in an amount exceeding 20% by weight, it is not preferable from the standpoint of stability and safety of the composition.

The composition according to one embodiment of the present invention may be an external preparation for skin. The external preparation for skin may be any kind applied to the outside of the skin, and various forms of cosmetics and medicines may be included therein.

In addition, the present invention can provide a cosmetic, a medicament or a health functional food composition comprising the composition containing the Piper longinmin as one embodiment.

The pharmaceutical composition according to an embodiment of the present invention may further contain a pharmaceutical adjuvant such as a preservative, a stabilizer, a wetting or emulsifying accelerator, a salt for controlling osmotic pressure and / or a buffer, and other therapeutically useful substances, May be formulated into various oral or parenteral dosage forms according to conventional methods.

Examples of the oral administration agent include tablets, pills, hard and soft capsules, liquids, suspensions, emulsions, syrups, powders, powders, granules, granules and pellets, , Diluents (such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and glycine), lubricants (such as silica, talc, stearic acid and magnesium or calcium salts thereof and polyethylene glycols) . The tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidine, optionally mixed with starch, agar, alginic acid or its sodium salt Such as disintegrants, absorbents, coloring agents, flavoring agents, and sweetening agents. The tablets may be prepared by conventional mixing, granulating or coating methods. In addition, it may be a transdermal dosage form in the form of parenteral administration. For example, it may be in the form of injections, drops, ointments, lotions, gels, creams, sprays, suspensions, emulsions, suppositories, But is not limited thereto.

The pharmaceutical composition according to an embodiment of the present invention may be administered by parenteral, rectal, topical, transdermal, subcutaneous, and the like.

The dosage of the active ingredient is within the level of those skilled in the art, and the daily dose of the drug depends on various factors such as the degree of progress of the subject to be administered, the age of onset, age, health condition, As a standard, it is generally possible to administer the composition at a dose of 1 / / kg to 200 mg / kg, preferably 50 / / kg to 50 mg / kg, once or twice a day, Are not intended to limit the scope of the present invention.

The cosmetic composition according to one embodiment of the present invention contains a cosmetically or dermatologically acceptable medium or base. It may be in any form suitable for topical application, for example, as a solution, a gel, a solid, a paste anhydrous product, an emulsion obtained by dispersing the oil phase in water, a suspension, a microemulsion, a microcapsule, In the form of a non-ionic follicle dispersing agent, or in the form of creams, skins, lotions, powders, ointments, sprays or conical sticks. These compositions may be prepared according to conventional methods in the art. The composition according to the invention may also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.

The cosmetic composition according to one embodiment of the present invention is not particularly limited in its formulation and may be, for example, softening lotion, convergent lotion, nutritional lotion, nutritional cream, massage cream, essence, eye cream, eye essence, , A cleansing foam, a cleansing water, a pack, a powder, a body lotion, a body cream, a body oil, and a body essence.

When the formulation of the present invention is a paste, cream or gel, animal fiber, plant fiber, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .

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 as a carrier component. In the case of a spray, in particular, / Propane or dimethyl ether.

In the case of the solution or emulsion of the present invention, a solvent, a solvent or an emulsifier is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.

When the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.

When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component is selected from aliphatic alcohol sulfates, aliphatic alcohol ether sulfates, sulfosuccinic acid monoesters, isethionates, imidazolinium derivatives, methyltaurate, sarcosinates, fatty acid amides Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, linolenic derivatives or ethoxylated glycerol fatty acid esters.

The cosmetic composition according to an embodiment of the present invention may further include components included in functional additives and general cosmetic compositions in addition to the extract containing the active ingredient. The functional additives may include water-soluble vitamins, oil-soluble vitamins, polymer peptides, polymeric polysaccharides, sphingolipids and seaweed extracts.

The cosmetic composition of the present invention may further contain, in addition to the above-described functional additive, components contained in a general cosmetic composition as required. Examples of the other ingredients that can be included in the composition include humectants, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbents, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, Accelerators, coolants, antiperspirants, purified water, and the like.

The health functional food composition according to one embodiment of the present invention may be in a liquid or solid form and may be in the form of tablets, capsules, soft capsules, pills, granules, beverages (drinks), diet bars, chocolates, And the formulation is not particularly limited. In the health food composition of the present invention, the health food composition may contain excipients, saccharides, fragrances, pigments, oils, proteins and the like as needed in addition to the active ingredients.

Hereinafter, the constitution and effects of the present invention will be described in more detail with reference to Examples and Experimental Examples. However, the following examples and experimental examples are provided for illustrative purposes only in order to facilitate understanding of the present invention, and the scope and scope of the present invention are not limited thereto.

[Experimental Example 1] Evaluation of melanin inhibitory activity 1

In order to evaluate the melanin production inhibitory effect of Piper longanmin, the following experiment was conducted.

First, B16 malignant melanoma (B16 melanoma) was seeded on a 12-well plate at 5 × 10 ⁴ / well and cultured for 24 hours at 10% CO ₂ at 37 ° C.

Subsequently, 500 nM of α-MSH (alpha melanocyte-stimulating hormone, Sigma Aldrich), which is a substance inducing the synthesis of tyrosinase as a negative control, was added to the cultured cells, and Kojic acid (Sigma Aldrich 100 ppm of Albutin (Sigma Aldrich), 100 ppm of Piperlongumine (Sigma Aldrich) as an example of the present invention, and 1, 2, and 3 μM of each of them were cultured in fresh medium for 72 hours.

After the treatment of the material was completed, the cells were washed with Dulbecco's Phosphate-Buffered Saline (DPBS). Then, 2 N NaOH (10% DMSO) was added and dissolved at 60 ° C for 1 hour. Cell lysate was transferred to a 96-well plate, absorbance was measured at 475 nm, and the amount of protein was measured.

The measured value was then calculated from the standard curve for synthetic melanin to the melanin content. The calculated melanin content was normalized to the total protein amount of each experimental group, and then the efficacy was evaluated in comparison with the control group. The results are shown in Table 1 and Fig. The t-test is the result of verifying the statistical significance between the reference (α-MSH in this experiment) and the experiment.

Control (cont) α-MSH (nM) Kojic acid (ppm) Arbutin (ppm) Piper Long Terminum (μM) - 500 100 100 One 2 3 Melanin / protein
(ppm / mg). 39.3 136.5 97.0 80.5 86.5 76.1 67.6 45.8 129.3 89.8 87.4 87.6 69.2 52.6 43.9 114.7 97.7 80.6 92.7 76.3 77.4 Average 43.0 126.8 94.8 82.8 88.9 73.9 65.9 Deviation 3.3 11.1 4.4 3.9 3.3 4.1 12.5 content%
(% of cont) 100 294.9 220.4 192.5 206.7 171.8 153.2 Deviation% 7.8 25.9 10.1 9.2 7.7 9.4 29.1 t-test standard 0.0097 0.0030 0.0048 0.0015 0.0032 ** ** ** ** **

(*: p <0.05, **: p <0.01, ***: p <0.001)

As shown in the results of Table 1 and Fig. 1, it was shown that Piperlongmin, the active ingredient of the composition according to the present invention, inhibited melanin induced by? -MSH in a concentration-dependent manner. In particular, Piper longingmin showed a similar or lower melanin content than 100 ppm of kojic acid and arbutin, even at a small amount of 1 to 3 μM. This means that Piper Longinum provides a remarkably good whitening efficacy even in small amounts.

[Experimental Example 2] Evaluation of melanin inhibitory activity 2

Since Piper longinum was developed as an anticancer drug, this experiment was carried out to evaluate the inhibitory effect of Piperlongmin on melanin formation in normal melanocyte cells other than B16 malignant melanoma cells.

First, melamine-a cell, a murine melanocyte cell line, was seeded on a 48-well plate at 1.5 × 10 ⁴ cells / well, and cultured in 10% CO ₂ , 37 ° C. Lt; / RTI &gt; for 24 hours.

Next, 50 ppm of Arbutin, 10, 100, 1000 nM of Piperlongumine as an example of the present invention, and 10 mg of Piper longum extract (Department of Botany) as a comparative example were added to the above- , University of Kerala, India), 10, 25, and 50 ppm, respectively, and cultured for 72 hours. Then, the above materials were treated again and cultured for 72 hours.

At this time, the pepper extract can be prepared by extracting the pulverized pepper fruit in a soxhlet extractor continuously using hexane, ethyl acetate and methanol for about 8 hours or more, and then concentrating under reduced pressure at a temperature of less than about 500 ° C (Beena Joy et al., Comparison and bioevaluation of Piper longum fruit extracts, J. Chem. Pharm. Res., 2010, 2 (4): 612-622). The contents of the above literature on the preparation of pepper extracts are incorporated herein by reference in their entirety.

After all of the treatment of the material was completed, the cells were washed with Dulbecco's Phosphate-Buffered Saline (DPBS). Then, 2 N NaOH (10% DMSO) was added and dissolved at 60 ° C for 1 hour. Cell lysate was transferred to a 96-well plate, absorbance was measured at 475 nm, and the amount of protein was measured.

The measured value was then calculated from the standard curve for synthetic melanin to the melanin content. The calculated melanin content was normalized to the total amount of protein in each experimental group, and the efficacy was evaluated in comparison with the control group. The results are shown in Table 2 and FIG.

Control (cont) Arbutin (ppm) Piper Long Terminals (nM) Pepper extract (ppm) - 50 10 100 1000 10 25 50 Melanin / protein
(ppm / mg). 184.1 95.3 162.8 154.7 130.2 149.3 111.2 103.3 168.4 102.1 170.1 147.8 123.0 166.7 121.5 123.2 163.2 97.5 161.3 153.9 131.7 151.5 130.4 106.7 Average 171.9 98.3 164.7 152.1 128.3 155.8 121.0 111.1 Deviation 10.9 3.5 4.7 3.8 4.7 9.5 9.6 10.7 content%
(% of cont) 100 57.2 95.8 88.5 74.6 90.6 70.4 64.6 Deviation% 6.3 2.0 2.8 2.2 2.7 5.5 5.6 6.2 t-test standard 0.00037 0.35396 0.04081 0.00309 0.12580 0.00372 0.00230 *** * ** ** **

(*: p <0.05, **: p <0.01, ***: p <0.001)

As shown in the results of Table 2 and FIG. 2, the effective ingredient of the composition according to the present invention, Piperlongmin, showed melanin production inhibitory effects in not only B16 malignant melanoma cells but also normal melamine-forming cells.

In addition, the extracts of Piper longongin and pepper extract inhibited melanin in a concentration-dependent manner. However, the concentration of Piper longingmin was about 0.3 ppm in terms of 1000 nM, so that the extracts of melanin at 10, 25 and 50 ppm It can be seen that the Piper longin of the present invention exhibits a whitening effect of about 500 times or more superior to the inhibition result. This is a very good value when compared with the result of the positive control arbutin 50 ppm.

Accordingly, it can be confirmed from the above results that Piper longinmin provides a remarkably excellent whitening effect even in a small amount.

[Experimental Example 3] Evaluation of melanin inhibitory activity 3

In order to confirm the excellent melanin production inhibitory effect of Piper longidone, an experiment for comparing melanin production inhibitory effects of Piperlongumine and Piperlonguminine (Cairo Chem Co., Ltd.) was conducted as follows.

First, melamine-a cell, a murine melanocyte cell line, was seeded on a 48-well plate at 1.5 × 10 ⁴ cells / well, and cultured in 10% CO ₂ , 37 ° C. Lt; / RTI &gt; for 24 hours.

Subsequently, 100 [mu] L of albutin, which is a whitening functional substance, as a positive control, and 1 [mu] M of Piperlongumine as an example of the present invention, and 10 ppm of Piperlonguminine as a comparative example, Each is treated with fresh medium and cultured for 72 hours. After 3 days, the materials are treated once more and then an additional 3 days are further cultured.

After the treatment of the material was completed, the cells were washed with Dulbecco's Phosphate-Buffered Saline (DPBS). Then, 2 N NaOH (10% DMSO) was added and dissolved at 60 ° C for 1 hour. Cell lysate was transferred to a 96-well plate, absorbance was measured at 475 nm, and the amount of protein was measured.

The measured value was then calculated from the standard curve for synthetic melanin to the melanin content. The calculated melanin content was normalized to the total protein amount of each experimental group, and then the efficacy was evaluated in comparison with the control group. The results are shown in Fig.

As shown in the results of FIG. 3, both of Piper longummin, an active ingredient of the composition according to the present invention, and Piper long guminin, a comparative example, inhibited melanin. However, Piper longummin showed melanin inhibition similar to that of arbutin, a positive control, while Piper longyminin, a comparative example, showed remarkably lower inhibition than twice.

In particular, since the comparative example of Piper long guminin is about 36.6 μM in terms of 10 ppm, it is compared with 1 μM of Piper long cannin and 1, 10 ppm of Piper long guminin, 3.66, 36.6 μM of Piper long guminin , It can be seen that the Piper longum of the present invention shows a whitening effect of about 10 times or more superior.

Accordingly, it can be confirmed from the above results that Piper longinmin provides a remarkably excellent whitening effect even in a small amount.

Claims (8)

A composition for whitening comprising Piperlongumine as an active ingredient. The composition according to claim 1, wherein the composition comprises 0.001 to 20% by weight of piper longinmin based on the total weight of the composition. 3. The whitening composition according to claim 2, wherein the composition comprises 0.01 to 15% by weight based on the total weight of the composition. The whitening composition according to claim 1, wherein the Piper longum compound inhibits the production of melanin. 5. A whitening pharmaceutical composition comprising the composition according to any one of claims 1 to 4. 5. A whitening cosmetic composition comprising the composition according to any one of claims 1 to 4. A whitening food composition comprising the composition according to any one of claims 1 to 4. 7. A whitening dermatological external preparation composition comprising the composition according to any one of claims 1 to 4.

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