KR101688815B1 - Composition containing propanoid derivatives for preventing gray hair and for treatment of leukoplakia - Google Patents

Abstract

More particularly, the present invention relates to a composition for preventing white spot and alleviating leukoplakia. More particularly, the present invention relates to a composition for treating melanocyte, comprising melanocyte- To a composition which promotes the onset of black blood and is also effective in the treatment of vitiligo.

Description

[0001] The present invention relates to a composition for prevention of white moth and for the treatment of leukoplakia containing a propanoid derivative,

More particularly, the present invention relates to a composition for preventing white spot and alleviating leukoplakia. More particularly, the present invention relates to a composition for treating melanocyte, comprising melanocyte- To a composition which promotes the onset of black blood and is also effective in the treatment of vitiligo.

Since white moth generally occurs when aging progresses, it gives strong impression of old age. Therefore, a lot of dyes have been studied for dyeing white moths in order to hide white moths. However, dyeing is a temporary method and must be stained again by the growth of white hair. In addition, oxidized black hair dye which is widely used at present causes skin damage by the use of an oxidizing agent and the like.

As an inhibitor of wheat bloom, black sesame seeds, horseradish, hanshiksu, and honey can be used as supplementary ingredients, such as Sukjipu, Chunmundong, and Maekmundong. The method of boiling at a temperature of 50 ° C and then keeping the black bean black in the chemical solution, using black sesame seeds, black sesame leaf, kelp, using aqua extract extract, using pituitary hormone, cAMP (3'-5 '-cyclic adenosine monophosphate), vitamin D3, and the like have been disclosed, but the effect that can be sensed is not shown.

Thus, the present inventors observed that a propanoid derivative substituted with a prenyl group has an effect of increasing the expression of MITF in a melanocyte-transforming cell line and inhibiting the progression of white moth in a vitiligo model mouse.

Accordingly, it is an object of the present invention to provide a composition for the prevention of white spot and for the treatment of vitiligo.

In order to achieve the above object, the present invention provides a composition for the prevention or treatment of alopecia, comprising a propanoid derivative substituted with a phenyl group as an active ingredient.

The composition of the present invention contains a propanoid derivative substituted with a phenyl group to increase the MITF expression of the melanocyte, thereby activating melanocytes and promoting melanin synthesis, thereby preventing the induction of white moths and promoting the onset of black cohosh, .

The composition for preventing white hair and treating leukosis according to the present invention contains a propanoid derivative substituted with a phenyl group as an active ingredient.

The propanoid derivative substituted with a phenyl group used in the present invention has a structure represented by the following formula (1)

From here,

R ₁ is H or -CH ₃ ,

R ₂ is H or -CH ₃ ,

R < ₃ > is H or -OH,

또는

이며,R ₄ is H, -OCH ₃ ,

or

Lt;

이고,X is H or

ego,

또는

이며,Y is H,

or

Lt;

,

,

,

또는

이고,
R₅는 H 또는 -CH₃이거나, Z와 직접결합으로 연결되어 고리를 형성할 수 있다.Z is H, -CH _3,

,

,

,

or

ego,
R ₅ is either H or -CH _3, are connected by a direct bond and Z may form a ring.

The propanoid derivative substituted with a phenyl group used in the present invention may be selected from the group consisting of broussonin A, brassonin B, brassonin C, brassonin D, bromonon E, brsonin F, kazinol C, It is preferable to use at least one selected from the group consisting of casinol D, casinol F, casinol G, casinol J, casinol K, casinol L, casinol M and casinol N, The casinol is shown in Table 1 below.

The propanoid derivatives substituted with the phenyl group of the present invention may be extracted from plants, synthesized, or commercially available ones. It is also preferable to use a pharmaceutical composition containing at least one of Bronosin A, Bronosin B, Bronosin C, Bronosin D, Bronosin E, Brosonin F, Cassinol C, Cassinol D, Cassinol F, Cassinol G, , Casinol L, casinol M and casinol N can be obtained from mulberry extracts. Mackerel roots used at this time can be used as long as they are in the mackerel tree. Specifically, mackerel (Broussonetia kazinoki Sieb), Broussonetia papyrifera Vent, and Broussonetia kazinoki var. Humilis can be used. The mulberry extract is not only contained in the leached liquid obtained by leaching from the mulberry tree, but also the concentrate obtained by partially or entirely concentrating the leach solution or the dregs, premix, seasoning, fluid extract and mulberry produced by drying the concentrate again It includes all of the plant itself as well as the chemicals that have the primary effect, and extracts from all parts of the mulberry tree, including stem, root, leaf, flower, and fruit, are available and are not limited to any particular part of the extract. In addition, a known method can be used for extracting the propanoid derivative substituted with the phenyl group from the mulberry extract.

Specifically, the mulberry extract can be extracted from mulberry leaves after extraction with water or an organic solvent by a method well known in the art. The organic solvent used in the present invention may be selected from the group consisting of ethanol, methanol, butanol, ether, ethyl acetate, chloroform and a mixed solvent of these organic solvents and water, preferably 80% ethanol. At this time, the extraction temperature is preferably 10 to 80 ° C, and the extraction can be performed for 3 to 24 hours. If the extraction temperature and the extraction time are exceeded, the extraction efficiency may be deteriorated or the component may be changed. The propanoid derivative substituted with a phenyl group used in the present invention may be obtained through synthesis according to a method known in the art, or a commercially available propanoid derivative may be purchased and used.

The cosmetic composition according to the present invention may contain the propanoid derivative substituted with the above-mentioned prenyl group in an amount of 0.001 to 50% by weight based on the total weight of the composition. If the content of the propanoid derivative substituted with the above-mentioned prenyl group is less than 0.001% by weight, the effect and effect of the above-mentioned components are insufficient. If the content is more than 50% by weight, skin safety or shape problems may occur.

The cause of white moths is the disappearance of melanocyte stem cells and the degradation of melanocytes. Especially, it is known that white moths caused by aging are mainly caused by loss of stem cells, and white moths including mites are caused by degradation of melanocytes due to environmental and mental stress of modern society.

The melanin synthesis activity of melanocytes is greatly influenced by the activity of MITF. The propanoid derivatives substituted with the prenyl group according to the present invention can significantly increase the expression of MITF in melanocytes to inhibit white moth .

When the composition of the present invention is applied to cosmetics, it may contain a cosmetically acceptable medium or base. It may be in any form suitable for topical application, for example as a solution, a gel, a solid or a paste anhydrous product, an emulsion obtained by dispersing an oil phase in water, a suspension, a microemulsion, a microcapsule, a microgranule or an ionic form (liposome) 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 also be prepared according to conventional methods in the art. In particular, the composition can be easily formulated into a formulation of shampoo, rinse, conditioning, tonic or scalp essence applied to scalp or hair. The composition according to the present invention may also be used in the form of a solution or suspension of the active compound of the present invention in the form of a lipid, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, a preservative, A lipid vesicle, or any other ingredient conventionally used in cosmetics, as well as adjuvants commonly used in the cosmetology field. These adjuvants are introduced in amounts commonly used in the cosmetics field.

When the composition of the present invention is applied to medicines, a propranoid derivative substituted with a prenyl group is used as an active ingredient, and an inorganic or organic carrier, which is commonly used, is added to the composition to form a parenteral administration (transdermal administration Or external application). Agents for parenteral administration include ointments, lotions, sprays, suspensions, and the like. The composition according to the present invention can be formulated according to a method commonly used in the art, and surfactants, excipients, coloring agents, spices, preservatives, stabilizers, buffers, suspending agents and other adjuvants can be suitably used.

The dosage of the composition according to the present invention may vary depending on the age, sex, body weight, the specific disease or condition to be treated, the severity of the disease or pathological condition, the route of administration and the judgment of the prescriber. Dosage determinations based on these factors are within the level of those skilled in the art and can be applied at the level of those skilled in the art, such as by topical application to the area where white moths or vitiligo occur. Generally, the dosage ranges from 0.001 mg / kg / day to about 2000 mg / kg / day. A preferred dosage is 200 [mu] g / kg / day to 5 mg / kg / day.

Hereinafter, the present invention will be described in more detail with reference to examples and test examples, but the present invention is not limited to these examples.

[Test Example 1] Promotion of MITF expression of a propanoid derivative substituted with a phenyl group using a transformed cell line

In order to confirm the effect of inhibiting the antimutagenic effect, the propynoid derivative substituted with the phenyl group was investigated for the promotion of MITF expression. To this end, a method for screening anti-whitening agents using transformed cell lines and albumin mice, Composition] (Application No. 10-2007-0072182) was used. The propanoid derivatives substituted with the phenyl group used in this test example were obtained from SIGMA, LANCASTER, and TCI. The melanoma melanocyte cell line MITF-GLuc (accession number: KCLRF-BP-00162) transformed with the expression vector pMITF-GLuc was incubated with 10% Fetal Bovine Serum (FBS), 100 units / ml penicillin-streptomycin (Gibco), 0.1μM TPA (Sigma ), 400μg / ml G418 is 37 ℃ in RPMI 1640 medium containing, 10% CO ₂ Lt; / RTI > A positive control, IBMX, was purchased from Sigma and used at a concentration of 100 μM. Transformed melanocytes (melan-a) were dispensed into 24-well microtiter plates at 50,000 cells / well. The next day, the treated cells were treated with a propranoid derivative substituted with the prenyl group shown in the following Table 2 as a test substance to a final concentration of 100 μM, treated with 0.1% DMSO as a negative control, 100 μM IBMX as a positive control, Lt; / RTI > for 3 days. After culturing, a small amount of glucose was transferred to a measuring plate and reacted with the substrate to quantify the amount of GLuc. Specifically, after transferring a small amount of the medium from the cell culture dish to a measuring plate, 1X GLUC asssy working solution (NEB) was added to the medium at a ratio of 4: 1, and the amount of light generated at 470 nM Were measured. The results are shown in Table 2 below.

Item Percent of Gluciferase production in negative control (%) The negative control (DMSO) 100 The positive control (100 [mu] M IBMX) 180 Brosonin A 150 Brosonin B 175 Brosonin C 190 Brosonin D 185 Brosonin E 176 Brosonin F 197 Casinol C 210 Casinol D 205 Casinol F 195 Casinol G 190 Casinol J 200 Casinol K 185 Casinol L 195 Casinol M 230 Casinol N 224

Table 2 shows that the propanoid derivatives substituted with a phenyl group promoted the expression of MITF in transgenic melanocytes. In comparison with the case of the positive control group IBMX, the MITF expression of transgenic melanocytes was significantly enhanced Is higher.

[Test Example 2] Evaluation of inhibition of white hair and induction of the effect of the propanoid derivatives substituted with in vivo prenyl group in white algae-stimulated albino mice

Vitiligo mice (C57bl / 6 ^- Mitf ^{mi - vit} ) were purchased from The Jackson Lab, USA. The anti-whiplash effect test method using the mouse in which the white moth is promoted is as follows. Dorsal hairs of 12-week-old mice were removed by depilation. However, the width of the hair removal area was adjusted to be the same for each individual. From the day after the hair was pulled out, twice a day, the anti-whiplash material was applied on the hairless area. A mixture of EtOH: 1,3-BG: DW = 3: 2: 5 (volume ratio) was used as the vehicle of the anti-whiplash material. The carrier was used as a negative control, and a solution containing 50 mM of IBMX As a control group, a solution prepared by adding the propanoid derivative substituted with the phenyl group shown in Table 3 at a concentration of 2.5% was used as a test group. After about 3 weeks, when the difference in antibacterial effect between the substances was visually recognized, newly-emerged hairs were collected and the amount of melanin in the hair was measured. The amount of melanin in hair was measured using the protein hydrolyzing enzyme Esperase (Novozyme). Reaction buffer was prepared by dissolving Esperase in a buffer (50 mM Tris-HCl, 5 mM DTT, pH 9.3) to a concentration of 1 NPU / ml. Five milligrams of mouse hair was added to 1 ml of reaction buffer and allowed to react for 13 hours at 37 ° C with shaking at 1,000 rpm. Then, the hair and the reaction solution were separated by an instant centrifugation. The reaction solution thus obtained is placed in a 96-well plate, and the amount of melanin in the reaction solution can be measured by measuring the absorbance at a wavelength of 405 nm. Table 3 shows the results of visual inspection and the measurement of melanin in hair when the negative control, positive control, and test group material were treated with a white algae-promoted black louse mouse model.

Item Percent of Melanin in Hair Determined to Negative Control Group (%) Negative control group 100 Positive control (IBMX) 105.9 Brosonin A 103.5 Brosonin B 105.1 Brosonin C 106.8 Brosonin D 106.4 Brosonin E 105.5 Brosonin F 107.4 Casinol C 112.5 Casinol D 109.8 Casinol F 110.4 Casinol G 111.5 Casinol J 109.4 Casinol K 105.8 Casinol L 110.6 Casinol M 118.5 Casinol N 114.5

According to Table 3, the propanoid derivatives substituted with a phenyl group were found to inhibit white hair in a mouse body promoted to white hair generation, increase the amount of melanin in the hair to promote black hair induction, and compared with the positive control group IBMX It is possible to effectively increase the amount of melanin.

[Test Example 3] Test for promoting melanin production of a propanoid derivative substituted with a phenyl group

Melanocytes (melan-a) were added to a 24-well microtiter plate at 50,000 cells / well in RPMI medium supplemented with 5% fetal bovine serum, 100 IU penicillin G and 0.2 μM TPA Respectively. The next day, the propranoid derivative substituted with a phenyl group as a test substance was treated with 100 μM of the final concentration, 0.1% DMSO was used as a negative control, 100 μM IBMX was used as a positive control, and the cells were incubated at 37 ° C. for 3 days Respectively. After incubation, the wells were washed with PBS, and 100 μl of 1N NaOH was added thereto, and melanin in the cells was dissolved. The absorbance of dissolved melanin was measured at 405 nm using a microplate reader. The measurement results of the melanin production promoting effect are shown in Table 4 below.

Item Percent of Melanin in Hair Determined to Negative Control Group (%) The negative control (DMSO) 100 Positive control (IBMX) 165 Brosonin A 140 Brosonin B 160 Brosonin C 170 Brosonin D 185 Brosonin E 160 Brosonin F 180 Casinol C 195 Casinol D 190 Casinol F 185 Casinol G 170 Casinol J 190 Casinol K 185 Casinol L 195 Casinol M 205 Casinol N 200

As shown in Table 4, the propanoid derivative substituted with a phenyl group promotes melanin synthesis of melanocytes, and it can increase the intracellular melanin level more effectively than IBMX, which is a positive control group, and is effective in improving vitiligo can confirm.

Claims (4)

A composition for the prevention or treatment of alopecia, comprising a propanoid derivative substituted with a phenyl group represented by the following formula (1) as an active ingredient:
[Chemical Formula 1]

From here,
R ₁ is H or -CH ₃ ,
R ₂ is H or -CH ₃ ,
R < ₃ > is H or -OH,
R ₄ is H, -OCH ₃ ,

or

Lt;
X is H or

ego,
Y is H,

or

Lt;
Z is H, -CH _3,

,

,

,

or

ego,
R ₅ is either H or -CH _3, are connected by a direct bond and Z may form a ring. The pharmaceutical composition according to claim 1, wherein the propanoid derivative substituted with a prenyl group is selected from the group consisting of Bronosin A, Bronosin B, Bronosin C, Bronosin D, Bronosin E, Bronosin F, Cassinol C, Wherein the composition is at least one selected from the group consisting of F, casinol G, casinol J, casinol K, casinol L, casinol M and casinol N. The composition according to claim 2, wherein the propanoid derivative substituted with a prenyl group is extracted from mulberry. The composition according to claim 1, wherein the propanoid derivative substituted with the phenyl group is contained in an amount of 0.001 to 50% by weight based on the total weight of the composition.