Combination of amla and hibiscus for inhibiting melanin production

Abstract

To provide a combination of amla and hibiscus for inhibiting melanin production.SOLUTION: The present invention provides a combination of amla and hibiscus for inhibiting melanin production.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a combination of amla and hibiscus for suppressing the production of melanin.

Background Art

[0002] Generally, melanin refers to a brown to black pigment biosynthesized by enzymatic and non-enzymatic oxidation, decarboxylation, and coupling reactions of phenols biosynthesized from tyrosine, and is widely distributed in animals and plants including the body surface, and is considered to play a role in absorbing excess light.

[0003] On the other hand, skin pigmentation such as freckles and lentigines is caused by the deposition of melanin produced from melanocytes. That is, when melanin is produced in excess, it induces pigmentation such as freckles and lentigines. As a measure to prevent or improve such skin pigmentation and achieve skin whitening, it is considered effective to suppress the production of melanin.

[0004] So far, various natural-derived components, arbutin, kojic acid, ascorbic acid, etc. have been reported as components having a melanin production inhibitory effect, and some of them have been formulated into various products such as cosmetics, foods, and pharmaceuticals and put into practical use.

[0005] For example, Patent Document 1 discloses a melanin production inhibitor containing a dinoflagellate extract.

[0006] Thus, various components having a melanin production inhibitory effect have been found, but their effects are not always sufficient, and the development of components and products with excellent melanin production inhibitory effects is still required.

Prior Art Documents

Patent Documents

[0007]

Patent Document 1

Summary of the Invention

[0008] The inventors of the present invention have found that the combination of amla and hibiscus effectively suppresses the production of melanin. The present invention is based on this finding.

[0009] Therefore, the present invention provides a combination of amla and hibiscus for suppressing the production of melanin.

[0010] According to the present invention, the following inventions are provided. (1) A composition for suppressing the production of melanin, comprising amla, for use in combination with hibiscus. (2) A composition for suppressing the production of melanin, comprising hibiscus, for use in combination with amla. (3) A composition for suppressing the production of melanin, comprising amla and hibiscus. (4) A composition for improving one or more selected from the group consisting of skin transparency, skin brightness, skin color yellowness, and skin color unevenness, comprising amla, for use in combination with hibiscus. (5) A composition for improving one or more selected from the group consisting of skin transparency, skin brightness, skin color yellowness, and skin color unevenness, comprising hibiscus, for use in combination with amla. (6) A composition for improving one or more selected from the group consisting of skin transparency, skin brightness, skin color yellowness, and skin color unevenness, comprising amla and hibiscus. (7) The composition according to any one of (1) to (6), wherein when the dry weight of amla is CA and the dry weight of hibiscus is CB, CA / CB is 0.3 to 2.5. (8) The composition according to any one of (1) to (7), which is an oral composition. Use of a combination of amla and hibiscus for the manufacture of a medicament for the purpose of suppressing the production of melanin. (10) Use of a combination of amla and hibiscus for the manufacture of a medicament for the purpose of improving one or more selected from the group consisting of skin transparency, skin brightness, skin color yellowness, and skin color unevenness. (11) The use according to (9) or (10), wherein when the dry weight of amla is CA and the dry weight of hibiscus is CB, CA / CB is 0.3 to 2.5. (12) The use according to any one of (9) to (11), wherein amla or hibiscus is in the form of an oral composition. (13) Use of a combination of amla and hibiscus for suppressing the production of melanin. (14) Use of a combination of amla and hibiscus for improving one or more selected from the group consisting of skin transparency, skin brightness, skin color yellowness, and skin color unevenness. (15) The use according to (13) or (14), wherein when the dry weight of amla is CA and the dry weight of hibiscus is CB, CA / CB is 0.3 to 2.5. (16) The use according to any one of (13) to (15), wherein amla or hibiscus is in the form of an oral composition. (17) A combination of amla and hibiscus for suppressing the production of melanin. (18) A combination of amla and hibiscus for improving one or more selected from the group consisting of skin transparency, skin brightness, skin color yellowness, and skin color unevenness. (19) The combination according to (17) or (18), wherein when the dry weight of amla is CA and the dry weight of hibiscus is CB, CA / CB is 0.3 to 2.5. (20) The combination according to any one of (17) to (19), wherein amla or hibiscus is in the form of an oral composition. (21) A method for suppressing the production of melanin in a subject, the method comprising administering an effective amount of a combination of amla and hibiscus. (22) A method for improving one or more selected from the group consisting of skin transparency, skin brightness, skin color yellowness, and skin color unevenness in a subject, the method comprising administering an effective amount of a combination of amla and hibiscus. (23) The method according to (21) or (22), wherein when the dry weight of amla is CA and the dry weight of hibiscus is CB, the administration is carried out so that CA / CB is 0.3 to 2.5. (24) The method according to any one of (21) to (23), wherein amla or hibiscus is in the form of an oral composition.

[0011] According to the present invention, a combination of amla and hibiscus for suppressing the production of melanin is provided. By using the combination of the present invention, it is possible to effectively suppress the production of melanin. BRIEF DESCRIPTION OF THE DRAWINGS

[0012]

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Figure 5

[0013] According to one aspect of the present invention, there is provided a melanogenesis inhibitor comprising amla, for use in combination with hibiscus or a composition comprising hibiscus. Such a melanogenesis inhibitor comprising amla may be a composition comprising amla for suppressing melanogenesis.

[0014] According to another aspect of the present invention, there is provided a melanogenesis inhibitor comprising hibiscus, for use in combination with amla or a composition comprising amla. Such a melanogenesis inhibitor comprising hibiscus may be a composition comprising hibiscus for suppressing melanogenesis.

[0015] According to another aspect of the present invention, there is provided a melanogenesis inhibitor comprising amla and hibiscus. Such a melanogenesis inhibitor comprising amla and hibiscus may be a composition comprising amla and hibiscus for suppressing melanogenesis.

[0016] In the present invention, the subjects to which the combination of amla and hibiscus is applied are not particularly limited, and examples include mammals such as humans, primates including chimpanzees, pet animals such as dogs and cats, livestock animals such as cows, horses, sheep, and goats, and rodents such as mice and rats. The subject to which the combination of amla and hibiscus in the present invention is preferably applied is a human.

[0017] Generally, the production of melanin involves the oxidation of tyrosine by copper ion-dependent tyrosinase in melanosomes within melanocytes, resulting in the production of dihydroxyphenylalanine (DOPA). Subsequently, DOPA is converted to dopaquinone by DOPA-oxidase, and then non-enzymatically polymerized in melanocytes to form dopachrome and indolequinone. The melanin produced in this way is called eumelanin (true melanin) and is black-brown. In addition to this true melanin, pheomelanin (sub-melanin), which is orange-red and biosynthesized from dopaquinone and cysteine via dihydrobenzothiazine, and trichochromes are also known as melanin.

[0018] Generally, when eumelanin forms and deposits in the skin, it has been reported that black pigmentation, increased dullness, decreased transparency, etc. occur, impairing beauty. Also, it has been reported that pheomelanin exhibits cytotoxicity such as enhanced oxidative stress and reduced activity of antioxidants in the living body. The melanin whose production is suppressed by the composition of the present invention is not particularly limited. Therefore, the composition of the present invention can improve these conditions.

[0019] The improvement in the present invention includes the state of a subject who is not in the same state as a healthy person returning to or approaching the state of a healthy person, or the state of a subject who is in the same state as a healthy person being maintained or becoming better than the state of a healthy person.

[0020] According to another aspect of the present invention, provided is an agent for improving at least one selected from the group consisting of skin transparency, skin brightness, skin yellow color, and skin color unevenness, the agent comprising amla and used in combination with hibiscus or a composition comprising hibiscus. Such an agent for improving at least one selected from the group consisting of skin transparency, skin brightness, skin yellow color, and skin color unevenness and comprising amla may be a composition comprising amla for improving at least one selected from the group consisting of skin transparency, skin brightness, skin yellow color, and skin color unevenness. Such improvement of at least one selected from the group consisting of skin transparency, skin brightness, skin yellow color, and skin color unevenness may be achieved by suppressing melanin production or may be achieved without suppressing melanin production, but is preferably achieved by suppressing melanin production.

[0021] According to another aspect of the present invention, provided is an agent for improving at least one selected from the group consisting of skin transparency, skin brightness, skin yellow color, and skin color unevenness, the agent comprising hibiscus and used in combination with amla or a composition comprising amla. Such an agent for improving at least one selected from the group consisting of skin transparency, skin brightness, skin yellow color, and skin color unevenness and comprising hibiscus may be a composition comprising hibiscus for improving at least one selected from the group consisting of skin transparency, skin brightness, skin yellow color, and skin color unevenness. Such improvement of at least one selected from the group consisting of skin transparency, skin brightness, skin yellow color, and skin color unevenness may be achieved by suppressing melanin production or may be achieved without suppressing melanin production, but is preferably achieved by suppressing melanin production.

[0022] According to another aspect of the present invention, there is provided at least one improving agent selected from the group consisting of skin transparency, skin brightness, skin yellow color, and skin color unevenness, which comprises amla and hibiscus. Such at least one improving agent selected from the group consisting of skin transparency, skin brightness, skin yellow color, and skin color unevenness, which comprises amla and hibiscus, may be a composition comprising amla and hibiscus for improving at least one selected from the group consisting of skin transparency, skin brightness, skin yellow color, and skin color unevenness. Such improvement of at least one selected from the group consisting of skin transparency, skin brightness, skin yellow color, and skin color unevenness may be achieved by suppressing melanin production, or may be achieved without suppressing melanin production, but is preferably achieved by suppressing melanin production.

[0023] The usage amounts of amla and hibiscus in the composition of the present invention can be appropriately determined according to the use. Preferably, when the dry weight of amla is CA and the dry weight of hibiscus is CB, CA / CB is 0.3 to 2.5, and more preferably, CA / CB is 0.5 to 1.5.

[0024] In the present invention, "amla" means Phyllanthus emblica or Emblica officinale (Chinese name: Amla), which is a plant of the genus Emblica in the Euphorbiaceae family, and is also called Indian gooseberry, oil plum, amalok, Malacca tree, etc. In the present invention, common amla can be used.

[0025] In the present invention, as the part of amla, for example, fruits (immature fruits, ripe fruits, dried fruits), leaves, tubers, flowers, seeds, etc. can be used, and preferably fruits are used. Also, in the present invention, amla itself (for example, fresh fruits) may be used.

[0026] In the present invention, amla can be used either raw or dried. According to one aspect of the present invention, "amla" is an amla extract produced using the whole amla or a part thereof.

[0027] "Hibiscus" in the present invention means Hibiscus sabdariffa or Hibiscus rosa-sinensis (Chinese name: Luo Shen Hua), which are plants of the genus Hibiscus in the family Malvaceae, and are also known as roselle and bush mallow, respectively. Generally, hibiscus is a plant native to Africa, and because of its fresh sour taste, it is also used as a sauce in French and Italian cuisine and is also used as a herb. In the present invention, common hibiscus can be used, and preferably roselle is used.

[0028] In the present invention, as parts of hibiscus, for example, flowers, sepals, buds, fruits, pericarp, seeds, seed coats, stems, leaves, branches, branch leaves, trunks, barks, roots, rhizomes, root barks, etc. can be used, and preferably sepals and / or flowers are used.

[0029] In the present invention, hibiscus can be used either raw, dried, or extracted with a solvent. According to one aspect of the present invention, "hibiscus" is a hibiscus extract produced using the whole hibiscus or a part thereof.

[0030] The method for producing the amla extract or hibiscus extract in the present invention is not particularly limited, and it can be produced according to the methods commonly used in the technical field. For example, it may be carried out by extracting the raw material amla or hibiscus. The extraction methods include, but are not limited to, for example, hot water extraction method, ultrasonic extraction method, filtration method, reflux extraction method, solvent extraction method, etc. These can be carried out alone or in combination of two or more methods. Also, in order to obtain a high-purity extract, the extract may be further extracted one or more times by the same method.

[0031] The type of solvent used for the production of the amla extract or hibiscus extract in the present invention is not particularly limited, and any solvent known in the art may be used as long as an extract having the object and effect of the present invention can be obtained. Examples of such solvents include, but are not limited to, water, hexane, ether, ethyl acetate, butanol, acetone, propanol, ethanol, methanol, propylene glycol, 1,3-butylene glycol, etc., and two or more of these may be used in combination.

[0032] When amla (including dried ones, extracts, etc.) or hibiscus (including dried ones, extracts, etc.) is commercially available, it may be used as long as the object and effect of the present invention can be obtained.

[0033] The composition of the present invention may be any of a pharmaceutical composition, a cosmetic composition, and a food composition, although not limited thereto. As the composition in the present invention, a food composition is preferably used.

[0034] The composition of the present invention may be either an oral composition or a topical composition. Amla and hibiscus in the present invention are preferably absorbed from the digestive tract by oral ingestion, and their active ingredients act in the body. Therefore, according to one preferred embodiment of the present invention, the composition of the present invention is an oral composition.

[0035] When the composition of the present invention is an oral composition, known components (additives) formulated in the oral composition can be further formulated. Such components are not particularly limited, and examples include emulsifiers, hydrating agents, solvents, emollients, stabilizers, thickeners, preservatives, lubricants, chelating agents, fillers, excipients, powders, fragrances, flavorings, absorbents, dyes, opacifiers, antioxidants, antiseptics, vitamins, amino acids, nutrients, minerals (electrolytes), flavorings such as synthetic flavorings and natural flavorings, pectic acid and its salts, alginic acid and its salts, organic acids, pH adjusters, glycerin, alcohol, carbonating agents used in carbonated beverages, etc.

[0036] The oral composition in the present invention may be any of a liquid, semi-solid, and solid.

[0037] When the composition of the present invention is used as a topical composition, known components (additives) formulated in the topical composition can be further formulated. Such components include, but are not limited to, for example, emulsifiers, hydrating agents, solvents, emollients, stabilizers, thickeners, preservatives, lubricants, chelating agents, fillers, excipients, powders, fragrances, flavorings, absorbents, dyes, opacifiers, antioxidants, vitamins, amino acids, and the like.

[0038] The topical composition in the present invention may be any of a liquid, semi-solid, and solid.

Example

[0039] The present invention will be specifically described based on the following examples, but the present invention is not limited to these examples. Unless otherwise specified, the content is expressed in mass%.

[0040] Agent applied to skin model The following substances listed in Table 1 below were used as drugs.

Table 1

[0041] Culture of skin model A stainless steel washer was placed in a 6-well plate, and 5 mL of a medium (EPI-100NMM, manufactured by Kurabo Industries Ltd.) warmed to 37°C was added to each well. Then, a culture cup containing a purchased three-dimensional skin model containing melanocytes (MEL-300, manufactured by Kurabo Industries Ltd.) was placed on it, and it was cultured at 37°C and 5% CO 2It was cultured in an incubator for 1 hour or more. After culturing, a drug was added to each well so that the amla extract became 60 μg / mL in dry weight in the medium, or the hibiscus extract became 30 μg / mL in dry weight in the medium, or the amla extract became 30 μg / mL in dry weight and the hibiscus extract became 15 μg / mL in dry weight in the medium, and it was incubated again. As a control, a medium without the drug was used.

[0042] The medium was changed every two days, and each drug or control was added so as to reach the concentration before medium change (the concentration at the time of drug addition) each time the medium was changed. The culture was carried out for 14 days after the start of culture.

[0043] Evaluation of the effect of the agent on melanin production in the skin model The amount of melanin in the skin model was measured by the following procedure. The culture cup containing the skin model was washed three times with PBS. After washing, the skin model was cut out from the culture cup, and each skin model was placed in a 1.5 mL tube with 200 μL of 1 M NaOH added so that the skin model was immersed in the NaOH, and it was left standing at 60 °C overnight. Then, after confirming that the skin model was completely dissolved (no residue remained), 100 μL of each sample solution was transferred to each well of a 96-well plate, the absorbance at 405 nm of each sample solution was measured, and the production amount of melanin was evaluated based on the measurement results.

[0044] For statistical processing, the Tukey-Kramer method was adopted as a multiple comparison test, and it was carried out by judging whether there was a significant improvement for the groups to be compared. The case of p < 0.05 was marked as *.

[0045] The measurement results are shown in Figure 1. It was confirmed that the group to which amla was applied alone and the group to which hibiscus was applied alone significantly suppressed melanin production compared to the control group. Also, it was shown that the group to which amla and hibiscus were applied in combination significantly suppressed melanin production compared to any of the control group, the group to which amla was applied alone, and the group to which hibiscus was applied alone.

[0046] Evaluation of the effects of amla and hibiscus on human skin color A combined test was conducted by panelists, and the effects of the present invention were confirmed by the following tests. For the combined test, four types of test samples (tablets) were prepared and implemented by being divided into groups A to D. The number of panelists was 15 in group A (placebo group), 15 in group B (60 mg (dry weight) of amla extract per day), 15 in group C (72 mg (dry weight) of hibiscus extract per day), and 15 in group D (30 mg (dry weight) of amla extract + 36 mg (dry weight) of hibiscus extract per day). The panelists were healthy Japanese women aged 35 to 50 who excluded those who met one or more of the conditions described in Table 2 below.

Table 2

[0047] Each panelist took the test sample (tablet) orally once a day, every day for 28 days, before going to bed with water or warm water. For the tablet, the amla extract described in Table 2 was used as amla, and the hibiscus extract described in Table 2 was used as hibiscus.

[0048] Questionnaire evaluation (Test method) Before the start of the combined test and 1 day, 3 days, 7 days, 14 days, 21 days, and 28 days after the start of the combined test, a questionnaire survey was conducted on items related to the color of human skin.

[0049] The questionnaire was evaluated using the VAS (abbreviation for visual analogue scale), which is widely used as an evaluation scale. That is, on each survey date, a sheet with a 10-cm horizontal straight line drawn on it was distributed to the subjects. With the left end of the straight line being defined as "the worst state" and the right end as "the best state", the subjects were asked to mark the position on the straight line according to the degree of actual feeling (the subjects mark a point on the line segment), and the distance moved to the right (or left) from the starting position of the test was evaluated as the scale value. The results of "skin transparency" are shown in Figure 2, the results of "skin brightness" are shown in Figure 3, the results of "skin yellow color" are shown in Figure 4, and the results of "skin color unevenness" are shown in Figure 5. In Figures 2 to 5, P represents the evaluation results of Group A (placebo), A represents the evaluation results of Group B (amla), H represents the evaluation results of Group C (hibiscus), and A + H represents the evaluation results of Group D (amla + hibiscus).

[0050] From the results in Figures 2 to 5, it was shown that Group D (amla + hibiscus) had an improvement effect on skin transparency, skin brightness, skin yellow color, and skin color unevenness compared with any of Group A (placebo), Group B (amla), and Group C (hibiscus). Also, such an effect of Group D (amla + hibiscus) was higher than the simple sum of the effects of Group B (amla) and Group C (hibiscus), indicating that the combination of amla and hibiscus had a synergistic effect on the improvement of skin transparency, skin brightness, skin yellow color, and skin color unevenness.

Claims

**Claim 1** A composition for suppressing melanin production, comprising amla, for use in combination with hibiscus. **Claim 2** A composition for suppressing melanin production, comprising hibiscus, for use in combination with amla. **Claim 3** A composition for suppressing melanin production, comprising amla and hibiscus. **Claim 4** A composition for improving one or more selected from the group consisting of skin transparency, skin brightness, skin color yellowness, and skin color unevenness, comprising amla, for use in combination with hibiscus. **Claim 5** A composition for improving one or more selected from the group consisting of skin transparency, skin brightness, skin color yellowness, and skin color unevenness, comprising hibiscus, for use in combination with amla. **Claim 6** A composition for improving one or more selected from the group consisting of skin transparency, skin brightness, skin color yellowness, and skin color unevenness, comprising amla and hibiscus. **Claim 7** The composition according to any one of claims 1 to 6, for use such that when the dry weight of amla is CA and the dry weight of hibiscus is CB, CA / CB is 0.3 to 2.

5. **Claim 8** The composition according to any one of claims 1 to 6, which is an oral composition.

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