Combination of lingonberry and hibiscus for inhibiting melanin production

Abstract

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

Description

Technical Field

[0001] The present invention relates to a combination of lingonberry 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, although various components having a melanin production inhibitory effect have been found, 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 present inventors have found that the combination of lingonberry 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 lingonberry 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 lingonberry, for use in combination with hibiscus. (2) A composition for suppressing the production of melanin, comprising hibiscus, for use in combination with lingonberry. (3) A composition for suppressing the production of melanin, comprising lingonberry and hibiscus. (4) A composition comprising lingonberry, for one or more selected from the group consisting of suppressing the darkness of skin color and improving skin complexion, for use in combination with hibiscus. (5) A composition comprising hibiscus, for one or more selected from the group consisting of suppressing the darkness of skin color and improving skin complexion, for use in combination with lingonberry. (6) A composition comprising lingonberry and hibiscus, for one or more selected from the group consisting of suppressing the darkness of skin color and improving skin complexion. (7) The composition according to any one of (1) to (6), wherein when the dry weight of lingonberry is CA and the dry weight of hibiscus is CB, CA / CB is 0.25 to 2 for use. (8) The composition according to any one of (1) to (7), which is an oral composition. (9) Use of a combination of lingonberry and hibiscus for the manufacture of a medicament for the purpose of suppressing the production of melanin. (10) Use of a combination of lingonberry and hibiscus for the manufacture of a medicament for the purpose of suppressing one or more selected from the group consisting of suppression of skin color darkness and improvement of skin complexion. (11) The use according to (9) or (10), for use such that when the dry weight of lingonberry is CA and the dry weight of hibiscus is CB, CA / CB is 0.25 to 2. (12) The use according to any one of (9) to (11), wherein the lingonberry or hibiscus is in the form of an oral composition. (13) Use of a combination of lingonberry and hibiscus for suppressing the production of melanin. (14) Use of a combination of lingonberry and hibiscus for one or more selected from the group consisting of suppression of skin color darkness and improvement of skin complexion. (15) The use according to (13) or (14), for use such that when the dry weight of lingonberry is CA and the dry weight of hibiscus is CB, CA / CB is 0.25 to 2. (16) The use according to any one of (13) to (15), wherein the lingonberry or hibiscus is in the form of an oral composition. (17) A combination of lingonberry and hibiscus for suppressing the production of melanin. (18) A combination of lingonberry and hibiscus for one or more selected from the group consisting of suppression of skin color darkness and improvement of skin complexion. (19) The combination according to (17) or (18), for use such that when the dry weight of lingonberry is CA and the dry weight of hibiscus is CB, CA / CB is 0.25 to 2. (20) The combination according to any one of (17) to (19), wherein the lingonberry or hibiscus is in the form of an oral composition. (21) A method for suppressing melanin production in a subject, the method comprising administering an effective amount of a combination of lingonberry and hibiscus. (22) A method for one or more selected from the group consisting of suppressing the darkness of skin color and improving skin blood color in a subject, the method comprising administering an effective amount of a combination of lingonberry and hibiscus. (23) The method according to (21) or (22), wherein when the dry weight of lingonberry is CA and the dry weight of hibiscus is CB, the administration is carried out such that CA / CB is 0.25 to 2. (24) The method according to any one of (21) to (23), wherein the lingonberry or hibiscus is in the form of an oral composition.

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

[0012]

Figure 1

Figure 2

Figure 3

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

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

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

[0016] In the present invention, the subjects to which the combination of lingonberry and hibiscus is applied are not limited, but include, for example, 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 lingonberry and hibiscus in the present invention is preferably applied is a human.

[0017] Generally, the production of melanin is carried out by oxidizing tyrosine by copper ion-dependent tyrosinase in melanosomes in melanocytes to produce dihydroxyphenylalanine (DOPA), which is further converted to dopaquinone by DOPA-oxidase, and then polymerized non-enzymatically in melanocytes to 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), trichochrome, etc., which are biosynthesized from dopaquinone and cysteine via dihydrobenzothiazine and are orange-red, are also known as melanin.

[0018] Generally, when eumelanin is formed and deposited 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 has cytotoxicity such as enhanced oxidative stress and decreased 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 that the state of a subject who is not in the same state as that of a healthy person returns to or approaches the state of a healthy person, or that the state of a subject who is in the same state as that of a healthy person is maintained or becomes better than the state of a healthy person.

[0020] According to another aspect of the present invention, there is provided an agent for suppressing the blackness of skin color and / or improving the skin blood color, comprising lingonberry, for use in combination with hibiscus or a composition comprising hibiscus. Such an agent for suppressing the blackness of skin color and / or improving the skin blood color comprising lingonberry may be a composition comprising lingonberry for one or more selected from the group consisting of suppressing the blackness of skin color and improving the skin blood color. Such suppression of the blackness of skin color and / or improvement of the skin blood color may be achieved by suppressing the production of melanin, or may be achieved without suppressing the production of melanin, but is preferably achieved by suppressing the production of melanin.

[0021] According to another aspect of the present invention, there is provided a skin color darkness inhibitor and / or skin blood color improver comprising hibiscus, for use in combination with lingonberry or a composition comprising lingonberry. Such a skin color darkness inhibitor and / or skin blood color improver comprising hibiscus may be a composition comprising hibiscus for one or more selected from the group consisting of suppression of skin color darkness and improvement of skin blood color. Such suppression of skin color darkness and / or improvement of skin blood color 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 a skin color darkness inhibitor and / or skin blood color improver comprising lingonberry and hibiscus. Such a skin color darkness inhibitor and / or skin blood color improver comprising lingonberry and hibiscus may be a composition comprising lingonberry and hibiscus for one or more selected from the group consisting of suppression of skin color darkness and improvement of skin blood color. Such suppression of skin color darkness and / or improvement of skin blood color 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 lingonberry and hibiscus in the composition of the present invention can be appropriately determined according to the application, but preferably, when the dry weight of lingonberry is CA and the dry weight of hibiscus is CB, CA / CB is 0.25 to 2, and more preferably, CA / CB is 0.4 to 1.3.

[0024] In the present invention, "lingonberry" refers to Vaccinium vitis-idaea, a plant of the genus Rhododendron in the Ericaceae family (Chinese name: bilberry), and is also called cowberry. Generally, lingonberries grow abundantly in the Arctic regions of northern Europe and Canada and are known to be rich in vitamin C and citric acid. The fruits are eaten raw and are commonly used in processed foods such as juice and jam. In the present invention, common lingonberries can be used.

[0025] In the present invention, as parts of lingonberries, for example, fruits (immature fruits, ripe fruits, dried fruits), leaves, tubers, flowers, seeds, etc. can be used, and preferably fruits are used.

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

[0027] In the present invention, "hibiscus" refers to Hibiscus sabdariffa or Hibiscus rosa-sinensis, plants of the genus Abelmoschus in the Malvaceae family (Chinese name: roselle), and are also called roselle and Chinese hibiscus respectively. Generally, hibiscus is a plant native to Africa and has a refreshing sour taste, so 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 in its raw form, dried form, or extracted form using a solvent. According to one aspect of the present invention, "hibiscus" is a hibiscus extract produced using the whole or a part of hibiscus.

[0030] The method for producing the cloudberry extract or hibiscus extract in the present invention is not particularly limited and can be produced according to methods commonly used in the art. For example, it may be carried out by extracting the raw material cloudberry or hibiscus. Examples of the extraction method include, but are not limited to, 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 producing the cloudberry 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 these may be used in combination of two or more.

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

[0033] The composition of the present invention may be any of, but not limited to, pharmaceutical composition, cosmetic composition, and food composition. 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. In the present invention, aronia and hibiscus 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 ingredients (additives) formulated in oral compositions can be further formulated. Such ingredients are not particularly limited, but 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, alcohols, carbonating agents used in carbonated beverages, and the like.

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

[0037] When the composition of the present invention is a topical composition, known ingredients (additives) formulated in topical compositions can be further formulated. Such ingredients 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 in any form of liquid, semi-solid, or solid.

Examples

[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] Agents Applied to the Skin Model The following agents listed in Table 1 below were used.

Table 1

[0041] Culture of the Skin Model Stainless steel washers were placed in a 6-well plate, and 5 mL of medium (EPI-100NMM, manufactured by Kurabo Industries Ltd.) warmed to 37°C was added to each well. Then, a culture cup containing the purchased three-dimensional skin model containing melanocytes (MEL-300, manufactured by Kurabo Industries Ltd.) was placed on top, and it was cultured in an incubator at 37°C and 5% CO 2 for 1 hour or more. After culturing, the agent was added to each well so that the dry weight of the lingonberry extract in the medium was 16.7 μg / mL, or the dry weight of the hibiscus extract in the medium was 30 μg / mL, or the dry weight of the lingonberry extract in the medium was 8.3 μg / mL and the dry weight of the hibiscus extract in the medium was 15 μg / mL, and it was incubated again. As a control, a medium without the agent was used.

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

[0043] Evaluation of the Effect of Agents on Melanin Production in the Skin Model The amount of melanin in the skin model was measured according to the following procedure. The culture cup containing the skin model was washed three times with PBS. After washing, the skin model was excised 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 left standing at 60 °C overnight. Then, after confirming that the skin model had completely dissolved (with no residue), 100 μL of each sample solution was transferred to each well of a 96-well plate, the absorbance of each sample solution at 405 nm was measured, and the amount of melanin production was evaluated based on the measurement results.

[0044] Statistical processing was performed by adopting the Tukey-Kramer method as a multiple comparison test and determining whether there was a significant improvement for the groups to be compared. The case of p < 0.05 was marked as *. Also, when 0.05 ≤ p < 0.1, it was judged that there was a significant tendency, It was designated as JPEG2025080656000002.jpg6169.

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

[0046] Evaluation of the Effects of Lingonberry and Hibiscus on Human Skin Color A panelist conducted a combined use test, and the effects of the present invention were confirmed by the following tests. For the combined use test, four types of test samples (tablets) were prepared and administered to groups A to D. The number of panelists was 15 in group A (placebo group), 15 in group B (50 mg (dry weight) of lingonberry extract per day), 15 in group C (72 mg (dry weight) of hibiscus extract per day), and 15 in group D (25 mg (dry weight) of lingonberry 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 lingonberry extract described in Table 2 was used as the lingonberry, and the hibiscus extract described in Table 2 was used as the hibiscus.

[0048] Questionnaire Evaluation (Test method) Before the start of the combined use test and 1 day, 3 days, 7 days, 14 days, 21 days, and 28 days after the start of the combined use 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 day, a sheet of paper with a 10-cm horizontal straight line drawn on it was distributed to the subjects. The left end of the straight line was marked as "the worst condition" and the right end as "the best condition", and the subjects were asked to mark the degree of actual feeling at a position on the straight line (the subjects mark a point on the line segment). The distance moved to the right (or left) from the starting position of the test was used as the scale value for evaluation. The results of "skin color darkness" are shown in Figure 2, and the results of "skin blood color" are shown in Figure 3. In Figures 2 and 3, P represents the evaluation result of Group A (placebo), L represents the evaluation result of Group B (lingonberry), H represents the evaluation result of Group C (hibiscus), and L + H represents the evaluation result of Group D (lingonberry + hibiscus).

[0050] From the results of Figures 2 and 3, it was shown that Group D (lingonberry + hibiscus) had an inhibitory effect on skin color darkness and an improvement effect on skin blood color compared with any of Group A (placebo), Group B (lingonberry), and Group C (hibiscus). Also, such an effect of Group D (lingonberry + hibiscus) was higher than the simple sum of the effects of Group B (lingonberry) and Group C (hibiscus), indicating that the combination of lingonberry and hibiscus had a synergistic effect on the inhibition of skin color darkness and the improvement of skin blood color.

Claims

**Claim 1** A composition for suppressing the production of melanin, comprising cloudberry, for use in combination with hibiscus. **Claim 2** A composition for suppressing the production of melanin, comprising hibiscus, for use in combination with cloudberry. **Claim 3** A composition for suppressing the production of melanin, comprising cloudberry and hibiscus. **Claim 4** A composition for use in one or more selected from the group consisting of suppressing the darkness of skin color and improving skin color, comprising cloudberry, for use in combination with hibiscus. **Claim 5** A composition for use in one or more selected from the group consisting of suppressing the darkness of skin color and improving skin color, comprising hibiscus, for use in combination with cloudberry. **Claim 6** A composition for use in one or more selected from the group consisting of suppressing the darkness of skin color and improving skin color, comprising cloudberry and hibiscus. **Claim 7** The composition according to any one of claims 1 to 6, for use such that CA / CB is 0.25 to 2, where CA is the dry weight of cloudberry and CB is the dry weight of hibiscus. **Claim 8** The composition according to any one of claims 1 to 6, which is an oral composition.

Images