Skin quality improver

Abstract

To provide a useful skin quality improving agent. [Solution] A skin quality improving agent containing, as an active ingredient, one or more compounds selected from the group consisting of (10E,12Z,14E)-9,16-Dioxooctadeca-10,12,14-trienoic acid (named saclipin B), (10E,12E,14E)-9,16-Dioxooctadeca-10,12,14-trienoic acid (named saclipin A), and derivatives thereof.

Description

[Technical Field]

[0001] The present disclosure relates to a skin quality improving agent. [Background technology]

[0002] Patent Document 1 describes an external skin preparation containing an extract of a plant of the genus Sphacele in the family Labiatae. This external skin preparation inhibits melanin production and has a tyrosinase activity inhibitory effect that is effective in preventing and improving post-sunburn pigmentation, age spots, freckles, melasma, etc., and is therefore effective in whitening the skin. It also inhibits elastase activity to restore and maintain skin firmness and elasticity, thereby preventing skin aging and maintaining a youthful skin state, and is also effective in preventing the oxidation of lipid components in the skin and preventing oxidative damage to the skin. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Japanese Patent Application Publication No. 11-92354 Summary of the Invention [Problem to be solved by the invention]

[0004] The present inventors have identified a drought-stress-inducible UV-absorbing substance in the cyanobacterium Aphanothece sacrum, and have explored the beneficial physiological activities of this substance and developed techniques for its effective use.

[0005] The present disclosure has been made in view of the above circumstances, and aims to provide a useful skin quality improving agent. [Means for solving the problem]

[0006] [1] A skin quality improving agent containing, as an active ingredient, one or more compounds selected from the group consisting of a compound represented by the following formula (1), a compound represented by the following formula (2), and derivatives thereof: [ka] [ka] [2] The skin quality improving agent according to [1], wherein the total amount of the compound represented by formula (1) and its derivatives is 20% by mass or more, when the total amount of the one or more compounds is 100% by mass. [3] A skin quality improving agent according to [1] or [2], which is used to inhibit skin aging. [4] A skin quality improving agent according to any one of [1] to [3], which is used for whitening. [5] A skin quality improving agent according to any one of [1] to [4], which is a topical skin preparation or cosmetic. [6] A skin quality improving agent according to any one of [1] to [5], which is an oral agent. [Brief explanation of the drawings]

[0007] [Figure 1] The upper panel is a chromatogram of the purified product of saclipin A, and the lower panel is a chromatogram of the purified product of saclipin B. [Figure 2] 1 is a graph showing the changes in the isomerization ratio and decomposition rate of purified saclipin products and extracts upon irradiation with light. [Figure 3] 1 is a graph showing the changes in isomerization ratio and decomposition rate of purified saclipin products and extracts upon heating. [Figure 4] 1 is a graph showing the results of measuring singlet oxygen quenching activity. [Figure 5] 1 is a graph showing the inhibition of elastase activity and the inhibition of tyrosinase activity. [Figure 6]1 is a graph showing the results of cell survival rate, collagen production rate, and hyaluronic acid production rate of dermal fibroblasts. [Figure 7] 1 is a graph showing the results of cell viability, melanin production rate, and melanin precursor (DHICA) darkening rate of B16 mouse melanoma cells. DETAILED DESCRIPTION OF THE INVENTION

[0008] Hereinafter, embodiments embodying the present disclosure will be described. In this specification, when a numerical range is indicated using "to" it is assumed that the range includes both the lower limit and the upper limit unless otherwise specified. For example, the expression "10 to 20" includes both the lower limit "10" and the upper limit "20". In other words, "10 to 20" has the same meaning as "10 or more and 20 or less". In addition, in this specification, the upper and lower limit values ​​of each numerical range can be combined in any way.

[0009] 1. Skin quality improver The skin quality improving agent of the present embodiment contains, as an active ingredient, one or more compounds selected from the group consisting of a compound represented by the following formula (1), a compound represented by the following formula (2), and derivatives thereof: [ka] [ka]

[0010] Hereinafter, the compound represented by the above formula (1) will also be referred to as saclipin B, and the compound represented by the above formula (2) will also be referred to as saclipin A. When there is no need to distinguish between saclipin A and saclipin B, they will also be referred to simply as saclipin. A derivative of the compound represented by the above formula (1) will also be referred to as a saclipin B derivative, and a derivative of the compound represented by the above formula (2) will also be referred to as a saclipin A derivative. The above "one or more compounds" will also be referred to as compound S.

[0011] (1) saclipin A, saclipin B Aphanothece sacrum is a cyanobacterium endemic to Japan, and has only been confirmed to exist in parts of Kyushu. Currently, it grows only in the wild at a farm using the Kogane River in Asakura City, Fukuoka Prefecture, and is distributed as a food product.

[0012] The inventors of the present application analyzed the extract of Aphanothece sacrum and found that there was a substance with strong absorption in the ultraviolet region. The substance with strong absorption in the ultraviolet region was isolated and purified by preparative HPLC, and structural analysis of the purified product revealed that it was the compound of formula (1) above and the compound of formula (2) above.

[0013] The compound represented by formula (1) is (10E,12Z,14E)-9,16-Dioxooctadeca-10,12,14-trienoic acid in the IUPAC nomenclature system. The molecular weight of this compound is 306. The inventors of the present application have named this compound saclipin B.

[0014] The compound represented by formula (2) is (10E,12E,14E)-9,16-Dioxooctadeca-10,12,14-trienoic acid in the IUPAC nomenclature system. The molecular weight of this compound is 306. The inventors of the present application have named this compound saclipin A. Saclipin A and saclipin B are geometric isomers (cis-trans isomers).

[0015] Figure 1 shows chromatograms obtained by HPLC analysis of purified saclipin A and purified saclipin B (described below). The measurement conditions for the HPLC analysis are as follows. In Figure 1, the peak at a retention time of 9.8 to 10.2 minutes is the saclipin A peak, and the peak at a retention time of 10.4 to 11.1 minutes is the saclipin B peak. [Measurement conditions] Detection wavelength: 320 nm Column: Inerteil ODS-P 3μm, 4.6X33 + 4.6X150mm Eluent: 50% acetonitrile (isocratic)

[0016] Thermodynamically, organic compounds with carbon-carbon double bonds are generally said to be more stable in the trans (E) form than in the cis (Z) form. It is surprising that Aphanothece saclipin B exists in addition to the trans (E) form of saclipin A. While the reason for the stability of saclipin B is unclear, it is possible that hydrogen bonding in the enol form stabilizes saclipin B. From the perspective of stability, saclipin B is a useful compound for a variety of applications.

[0017] Saclipin A and / or saclipin B may be used in the form of an extract from cyanobacteria or in the form of a purified product. The purification method is not particularly limited and can be performed, for example, by a chromatography method such as HPLC. It has been confirmed that saclipin A and / or saclipin B can contribute to improving skin quality whether in the form of an extract from cyanobacteria or in the form of a purified saclipin A and / or saclipin B product. From the viewpoint of safety for the human body, the extract is preferably an extract obtained by extraction with ethanol. When used in the form of an extract from cyanobacteria, it is advantageous in that the purification step can be omitted.

[0018] (2) Saclipin A derivatives, saclipin B derivatives In the present disclosure, a saclipin B derivative refers to a derivative in which one or more functional groups present in saclipin B have been modified, and which has functionality equivalent to or greater than that of saclipin B. A saclipin A derivative refers to a derivative in which one or more functional groups present in saclipin A have been modified, and which has functionality equivalent to or greater than that of saclipin A. The above-mentioned "functionality" is not particularly limited, and examples include singlet oxygen digestion ability, tyrosinase inhibitory activity, elastase inhibitory activity, melanin production inhibitory ability, melanin production inhibitory ability, and melanin precursor (DHICA) darkening inhibitory ability.

[0019] The saclipin B derivative is preferably one or more selected from the group consisting of an ester derivative obtained by reacting the terminal carboxyl group of saclipin B with an alcohol, an amide derivative obtained by reacting the terminal carboxyl group of saclipin B with an amine, and an ammonium salt obtained by reacting the terminal carboxyl group of saclipin B with ammonium. The saclipin A derivative is preferably one or more selected from the group consisting of an ester derivative obtained by reacting the terminal carboxyl group of saclipin A with an alcohol, an amide derivative obtained by reacting the terminal carboxyl group of saclipin A with an amine, and an ammonium salt obtained by reacting the terminal carboxyl group of saclipin A with ammonium. The type of carboxyl derivative group in the saclipin B derivative and / or saclipin A derivative can be appropriately selected depending on the intended use, dosage form, etc.

[0020] The carboxyl group derivative group is, for example, -COOR 1 , -CONH2, -CONHR 2 , -CONR 3 R 4 , -COONH4, -COONH3R 5 where R 1 , R 2 , R 3 , R 4 , R 5are each independently a hydrocarbon group having 1 to 10 carbon atoms, which may have a functional group. Among the carboxyl group derivative groups, saclipin B having -COOCH3 and saclipin A having -COOCH3 are also referred to as methyl-esterified saclipin B and methyl-esterified saclipin A. Methyl-esterified saclipin B and methyl-esterified saclipin A can enhance hydrophobicity while maintaining UV absorbency equivalent to that of saclipin B and saclipin A. Such saclipin B derivatives and / or saclipin A derivatives are more suitable for use as mixtures with hydrophobic components such as oils than saclipin B and / or saclipin A.

[0021] (3) Isomer ratio The ratio of saclipin A and derivatives thereof to saclipin B and derivatives thereof in the skin quality improving agent is not particularly limited. The ratio of saclipin A and derivatives thereof to saclipin B and derivatives thereof in the skin quality improving agent (saclipin A and derivatives thereof:saclipin B and derivatives thereof, mass ratio) can be, for example, 80:20 to 5:95, or may be 70:30 to 5:95, 60:40 to 5:95, 50:50 to 8:92, 40:60 to 8:92, or 30:70 to 10:90. In the Examples described below, the ratio of saclipin A to saclipin B in an extract of Aphanothece saclipa that was not subjected to isomerization treatment was 92.8:7.2.

[0022] It has been found that saclipin B has a stronger tyrosinase activity inhibitory effect and hyaluronic acid production promoting effect than saclipin A. Therefore, it is preferable that the skin quality improving agent contains at least one of saclipin B and a saclipin B derivative. The total amount of saclipin B and its derivatives is preferably 20% by mass or more, more preferably 30% by mass or more, even more preferably 40% by mass or more, and may be 50% by mass or more, 60% by mass or more, or 70% by mass or more, when the entire compound S is taken as 100% by mass. The upper limit of the total amount of saclipin B and its derivatives may be 100% by mass, and is usually 95% by mass or less.

[0023] Saclipin B can be obtained by isomerizing saclipin A. The isomerization treatment is not particularly limited. For example, the isomerization treatment may be light irradiation treatment or heat treatment. From the viewpoints of isomerization efficiency and residual rate, the isomerization treatment is preferably light irradiation treatment. For example, light irradiation treatment is a treatment in which saclipin A solution is irradiated with light to isomerize saclipin A to saclipin B. The solvent for the saclipin A solution is not particularly limited. Examples of the solvent include methanol, ethanol, and acetonitrile. The extraction solvent used to extract saclipin A and saclipin B from cyanobacteria may be used as the solvent for the light irradiation treatment. That is, a saclipin A extract may be subjected to light irradiation treatment to obtain an extract enriched in saclipin B (a saclipin B extract described below).

[0024] The conditions for light irradiation are not particularly limited. The illuminance of light irradiation can be, for example, 4,000 lux or more and 40,000 lux or less. The temperature during light irradiation can be, for example, 4°C or more and 40°C or less. The light irradiation time can be, for example, 12 hours or more and 48 hours or less.

[0025] In Experiment 1, described below, an experiment was conducted to isomerize saclipin (purified product, ethanol solution) with a saclipin A:saclipin B ratio of 84:16 by light irradiation at 30°C using a fluorescent lamp of approximately 33,000 lux as a light source. The isomerization reaction was completed in approximately 2 hours. The saclipin A:saclipin B ratio was approximately 15:85. Under the above light irradiation conditions, saclipin A and saclipin B were hardly decomposed even after 8 hours of irradiation. These results demonstrate that the saclipin isomerization technology by light irradiation is suitable for use as a skin quality improving agent.

[0026] 2. Actions and uses of skin quality improvers Signs of aging, such as age spots, wrinkles, and sagging skin, are observed. Tyrosinase activity in melanocytes plays an important role in age spots, i.e., the accumulation of melanin in the epidermis. Furthermore, the loss of skin elasticity (firmness), which is one of the causes of wrinkles and sagging, is thought to be related to elastase activity, which breaks down elastic fibers (elastin) produced by dermal fibroblasts. Furthermore, while it is said that approximately 80% of wrinkles and sagging are caused by photoaging due to long-term exposure to UV rays, it is known that various phenomena induced in the skin by UV rays are mediated by reactive oxygen species. Therefore, elimination of reactive oxygen species plays an important role in preventing photoaging. Additionally, wrinkles, sagging skin, and fine lines observed in aging skin are thought to be caused in part by a decrease in skin elasticity (firmness), loss of flexibility, and dryness. In particular, collagen produced by dermal fibroblasts is thought to play an important role in skin firmness, while hyaluronic acid produced by fibroblasts plays an important role in skin flexibility and moisture. Many factors contribute to the development of dark spots and dullness, two of the most common skin concerns. Excessive melanin production by epidermal pigment cells (melanocytes)—whether globally or in specific areas—can contribute to dullness and dark spots. The oxidative polymerization of DHICA (5,6-dihydroxyindole-2-carboxylic acid), a melanin precursor, is also a necessary step in the production of dark melanin.

[0027] (1) Antioxidant effect Saclipin A has singlet oxygen quenching activity. Saclipin B has singlet oxygen quenching activity. Saclipin A, the trans isomer, exhibits higher singlet oxygen quenching activity than saclipin B, the cis isomer. Similarly, saclipin A derivatives and saclipin B derivatives are also expected to have singlet oxygen quenching activity. Saclipin A derivatives, which are trans isomers, are expected to exhibit higher singlet oxygen quenching activity than saclipin B derivatives, which are cis isomers. It is known that various skin-related phenomena, such as age spots, wrinkles, loss of firmness and elasticity, dullness, and rough skin, are mediated by reactive oxygen species. Skin quality improvement agents containing the above-mentioned compound S are expected to contribute to the prevention and improvement of skin disorders caused by reactive oxygen species generated by, for example, ultraviolet radiation.

[0028] (2) Anti-aging effect Saclipin A has the effect of inhibiting elastase activity. Saclipin B also has the effect of inhibiting elastase activity. The elastase activity inhibitory effects of saclipin A and saclipin B are approximately equivalent. Similarly, saclipin A derivatives and saclipin B derivatives are presumed to have the effect of inhibiting elastase activity. When saclipin A and / or saclipin B are used in the form of a cyanobacterial extract, the elastase inhibitory effect can be enhanced compared to when saclipin A and / or saclipin B are used in the form of a purified product. Although the reason for this is unclear, it is possible that components other than saclipin A and / or saclipin B contained in the cyanobacterial extract contribute to the enhanced elastase inhibitory effect. Considering the results of Experiment 4 (elastase inhibitory activity) described below, it is speculated that saclipin is responsible for the majority of the elastase inhibitory activity of the cyanobacterial extract.

[0029] Saclipin A has the effect of promoting collagen production in dermal fibroblasts. Saclipin B also has the effect of promoting collagen production in dermal fibroblasts. The effects of saclipin A and saclipin B on promoting collagen production in dermal fibroblasts are approximately equivalent. Similarly, saclipin A derivatives and saclipin B derivatives are presumed to have the effect of promoting collagen production in dermal fibroblasts. When saclipin A and / or saclipin B are used in the form of an extract from cyanobacteria, the collagen production-promoting effect of dermal fibroblasts can be enhanced compared to when saclipin A and / or saclipin B are used in the form of a purified product.

[0030] Saclipin B promotes hyaluronic acid production in dermal fibroblasts. On the other hand, saclipin A does not show a significant promoting effect on hyaluronic acid production in dermal fibroblasts. Similarly, saclipin B derivatives are presumed to promote hyaluronic acid production in dermal fibroblasts. Saclipin A derivatives may not show a significant promoting effect on hyaluronic acid production in dermal fibroblasts. However, saclipin A and saclipin A derivatives contained in skin quality improvement agents may be isomerized to saclipin B and saclipin B derivatives under the conditions of use, and may exhibit a promoting effect on hyaluronic acid production. When saclipin A and / or saclipin B are used in the form of an extract from cyanobacteria, the effect of promoting hyaluronic acid production in dermal fibroblasts can be enhanced compared to when saclipin A and / or saclipin B are used in the form of a purified product.

[0031] Furthermore, when saclipin A or saclipin B was used in the form of a purified product, there was no effect on the viability of dermal fibroblasts up to a concentration of 20 μM. It was found that when saclipin A or saclipin B was used in the form of an extract from cyanobacteria, it affected the viability of dermal fibroblasts in a concentration-dependent manner. When used in the form of an extract from cyanobacteria, it is desirable to use it in a skin quality improving agent at a concentration range that does not affect cell viability.

[0032] From the above, a skin quality improving agent containing the above-mentioned compound S as an active ingredient is suitably used for inhibiting skin aging. The skin quality improving agent containing the above-mentioned compound S as an active ingredient is also useful as a skin aging inhibitor, an elastase activity inhibitor, a tyrosinase activity inhibitor, a collagen production promoter, and a hyaluronic acid production promoter.

[0033] (3) Whitening effect Saclipin A has the effect of inhibiting tyrosinase activity. Saclipin B also has the effect of inhibiting tyrosinase activity. Saclipin B, which is a cis isomer, exhibits a stronger inhibitory effect on tyrosinase activity than saclipin A, which is a trans isomer. Similarly, saclipin A derivatives and saclipin B derivatives are also expected to have the effect of inhibiting tyrosinase activity.

[0034] Saclipin A has the effect of suppressing melanin production. Saclipin B also has the effect of suppressing melanin production. The effects of saclipin A and saclipin B on suppressing melanin production are approximately equivalent. Similarly, saclipin A derivatives and saclipin B derivatives are presumed to have the effect of suppressing melanin production. When saclipin A and / or saclipin B are used in the form of an extract from cyanobacteria, the effect of inhibiting melanin production can be enhanced compared to when saclipin A and / or saclipin B are used in the form of a purified product.

[0035] When saclipin A and / or saclipin B are used in the form of an extract from cyanobacteria, the saclipin A extract has the effect of inhibiting the darkening of melanin precursor (DHICA).When saclipin A and / or saclipin B are used in the form of an extract from cyanobacteria, the saclipin B extract has the effect of inhibiting the darkening of melanin precursor (DHICA).However, when saclipin A and / or saclipin B are used in the form of a purified product, they do not exhibit a significant inhibitory effect on the darkening of melanin precursor (DHICA).

[0036] From the above, a skin quality improving agent containing the above-mentioned compound S as an active ingredient is suitably used for whitening. The skin quality improving agent containing the above-mentioned compound S as an active ingredient is also useful as a skin whitening agent, a tyrosinase activity inhibitor, a melanin production inhibitor, and an inhibitor of darkening caused by melanin precursor (DHICA).

[0037] (4) Skin care products or cosmetics The skin quality improving agent of the present disclosure is useful, for example, as a topical skin preparation or cosmetic. It is believed that when Compound S is applied topically, its efficacy is more efficiently exerted than when it is taken orally. In addition to the above-mentioned components, the topical skin preparation or cosmetic of the present disclosure may contain, as appropriate, components commonly used in topical skin preparations or cosmetic preparations, such as aqueous components, surfactants, oily components, moisturizers, polymers, powders, pigments, UV absorbers, film-forming agents, pH adjusters, anti-fading agents, antioxidants, antifoaming agents, cosmetic ingredients, preservatives, and fragrances, within quantitative and qualitative ranges that do not impair the effects of the present disclosure, in order to impart various effects. The form of the topical skin preparation or cosmetic is not particularly limited, and may be any of liquid, gel, cream, semi-solid, solid, stick, powder, etc. Examples of topical skin preparations or cosmetics include pharmaceuticals and other topical skin preparations and cosmetics, such as topical solid preparations, topical liquid preparations, sprays, ointments, creams, gels, patches, emulsions, lotions, beauty serums, beauty oils, pack cosmetics, facial cleansers, massage cosmetics, makeup bases, body cosmetics, hair cosmetics, bath additives, etc. Meanwhile, the form of the topical skin preparation or cosmetic of the present disclosure may be any of oil-in-water (o / w, w / o / w) type, water-in-oil type, multiple emulsions, microemulsions, oil suspensions, etc., and can be appropriately selected depending on the application and purpose. The method for producing the topical skin preparation or cosmetic is not particularly limited, and methods typically used for producing topical skin preparations or cosmetics can be used.

[0038] The amount of the compound S in the topical skin preparation or cosmetic is not particularly limited and can be appropriately determined depending on the application. From the viewpoints of usability such as storage and ease of application, and obtaining a skin improving effect, the amount of the compound S in the topical skin preparation or cosmetic is preferably 0.01% to 20%, and more preferably 0.1% to 10%, when the mass of the entire preparation is taken as 100%. The amount and method of application of the topical skin preparation or cosmetic composition are not particularly limited, and it can generally be used by applying, for example, painting, an appropriate amount to the outer skin such as the skin several times a day.

[0039] (5) Oral medication The skin quality improving agent of the present disclosure is also useful as an oral agent, for example. When the above-mentioned compound S is orally ingested, it is believed that its efficacy is more efficiently exerted on deep fibroblasts, which are difficult to reach when applied topically. Oral Agent The oral agent of the present disclosure can appropriately contain, in addition to the above-mentioned components, components used in ordinary oral agents, etc., within quantitative and qualitative ranges that do not impair the effects of the present disclosure. The form of the oral agent is not particularly limited, and it can be added or enclosed in any form, such as tablets, capsules, granules, powders, tablets, jellies, gummies, gums, drinks, or PET bottles, or can be added to any food or drink. The oral agent is suitable as an oral agent such as a pharmaceutical, functional food, supplement, food additive, etc.

[0040] The amount of compound S in the oral preparation is not particularly limited and can be appropriately determined depending on the application. From the viewpoints of storage stability, ease of ingestion, and skin improving effect, the amount of compound S in the oral preparation is preferably 0.01% to 10%, and more preferably 0.1% to 5%, when the mass of the entire oral preparation is taken as 100%. The dosage of the oral preparation can be appropriately changed depending on factors such as the age, weight, sex, and condition of the person taking it. For example, the daily intake of the oral preparation is 0.001 mg to 100 mg, preferably 0.005 mg to 70 mg, more preferably 0.01 mg to 50 mg, and even more preferably 0.1 mg to 20 mg, per adult weighing 60 kg, calculated as the above-mentioned compound S, but is not limited to these ranges. If necessary, the above-mentioned intake amount can be taken once or several times a day, for example, in divided doses divided into 2 to 3 times. [Example]

[0041] The present disclosure will be described in more detail below with reference to examples, although the scope of the present disclosure is not limited to these examples.

[0042] 1. Sample Preparation (1) Purified saclipin A and purified saclipin B Ten grams of dried A. sacchariflorus (product name: "Jusen-Koke", sold by Endo Kinsen-do) was ground using a food processor (IFM-C20G, manufactured by Iwatani Co., Ltd.). 50 mL of methanol was added to the resulting powder, and the mixture was sonicated using an ultrasonicator, Model UR-200P (Tomy Seiko). The resulting suspension was centrifuged at 2330 × g for 15 minutes at 4 °C, and the resulting supernatant was dried in a centrifugal concentrator, VC-36R (Taitec), in the dark. The resulting dried material was dissolved in 5 mL of acetonitrile / formic acid / water (55 / 0.1 / 44.9, v / v / v) and passed through a 0.22 μm pore size filter. This sample was subjected to preparative HPLC using an Inertsil ODS-3 column (10 μm particle size; 50 mm i.d. × 20 mm, GL Sciences) connected to another Inertsil ODS-3 column (10 μm particle size; 250 mm i.d. × 20 mm, GL Sciences). The mobile phase was acetonitrile / formic acid / water (55 / 0.1 / 44.9, v / v / v) and run at a flow rate of 6.0 mL / min. Compound elution was monitored at a detection wavelength of 320 nm. In this preparative HPLC, saclipin A and saclipin B eluted in the same fraction. The eluted fraction was lyophilized. All of the above purification steps were performed in the dark. The resulting sample contained saclipin A and saclipin B in a ratio of approximately 86:14 (see Figure 1). This was used as the purified saclipin A product.

[0043] Purified saclipin B was prepared by dissolving purified saclipin A in ethanol and irradiating it with 6000 lux of white light for 24 hours to isomerize saclipin A to saclipin B. The resulting sample contained saclipin A and saclipin B in a ratio of approximately 8:92 (see Figure 1). This was used as the purified saclipin B.

[0044] (2) Extract of saclipin A, extract of saclipin B The saclipin A extract was obtained by crushing dried A. saclipin A. saclipin A (product name: "Jusen-Koke", sold by Endo Kinsen-do) in a food processor (IFM-C20G, Iwatani Co., Ltd.) and extracting it with ethanol. Specifically, 3.0 g of the resulting powder was transferred to a 50 mL glass vial, and 30 mL of ethanol was added. Extraction was performed on ice (approximately 5°C) using an ultrasonicator CPX1800H-J (Yamato Scientific Co., Ltd.) at 70 W, 40 kHz, and 20 minutes. The extraction residue was removed using a polytetrafluoroethylene (PTFE) filter (0.22 μm pore size, Osaka Chemical Co., Ltd.). The resulting filtrate was used as the saclipin A extract.

[0045] The saclipin B extract was prepared by irradiating the above saclipin A extract with 6000 lux of white light for 24 hours to isomerize saclipin A to saclipin B.

[0046] 2. Experiment 1 (Photoisomerization test, thermal isomerization test) (1) Photoisomerization test, thermal isomerization test Samples of purified saclipin A and saclipin A extract were dissolved in ethanol to a saclipin concentration of 10 μM and placed in 10 mL glass vials. The atmosphere was replaced with nitrogen, and the vials were sealed with caps. For photostability testing, the vials were stored at 30°C for 8 hours under light irradiation using a fluorescent lamp (EFG25ED / 21-G101, Asahi Electric Co., Ltd.) with a light intensity of approximately 33,000 lux. For thermal stability testing, the vials were stored in the dark at 30°C, 50°C, and 70°C for 14 days.

[0047] (2) Evaluation of Experiment 1 (photoisomerization test, thermal isomerization test) The rate constant (k; min) for the isomerization reaction of the trans isomer saclipin A to the cis isomer saclipin B -1 ) was evaluated. The following first-order kinetic model was used to estimate the isomerization rate constant (k) of saclipin:

number

[0048] Furthermore, based on the rate constant (k) at different temperatures (30°C, 50°C, 70°C), the activation energy (Ea) for the thermal isomerization of saclipin A to saclipin B was calculated using the Arrhenius equation as follows:

number

[0049] Before treatment and after treatment for a predetermined time, HPLC analysis was performed under the following measurement conditions to calculate the amounts of saclipin A and saclipin B, and the isomerization rate of saclipin A was calculated. [Measurement conditions] Detection wavelength: 320 nm Column: Inerteil ODS-P 3μm, 4.6X33 + 4.6X150mm Eluent: 50% acetonitrile (isocratic)

[0050] The remaining rates of saclipin A and saclipin B after treatment for a predetermined time were calculated using the following formula: In the formula, "peak area" is the sum of the peak area of ​​saclipin A and the peak area of ​​saclipin B. Residual rate of saclipin (%) = (peak area after treatment / peak area before treatment) × 100

[0051] (3) Results of Experiment 1 (Photoisomerization Test, Thermal Isomerization Test) The results of Experiment 1 are shown in Figures 2 and 3. The horizontal axis of the graph in Figure 2 indicates the time (minutes) of light irradiation treatment. The horizontal axis of the graph in Figure 3 indicates the time (days) of heat treatment. The vertical axes of the graphs in Figures 2A and C and Figures 3A and C indicate the proportion of the isomer. The vertical axes of the graphs in Figures 2B and D and Figures 3B and D indicate the residual rate (%) of saclipin.

[0052] In the isomerization by light irradiation treatment, the isomerization reaction of saclipin reached a plateau in about 5 hours. At that time, the ratio of saclipin A to saclipin B was approximately 15:85. This isomer ratio was maintained thereafter (Fig. 2A and C). These isomerization characteristics were similar between the purified saclipin A product and the saclipin A extract. The photoisomerization rate constants (k) of the purified saclipin A product and the saclipin A extract were calculated to be 2.9 × 10, respectively, using a first-order kinetic model. -2 (s -1 ) and 3.0 × 10 -2 (s -1 ) was calculated.

[0053] The residual rate of saclipin increased approximately 6 to 8 hours after the start of light exposure (Figure 2B and D). This is due to the increased sensitivity of HPLC detection associated with the isomerization of saclipin A to B. This is likely due to the higher molar extinction coefficient of saclipin B compared with that of saclipin A. This result suggests that 8 hours of light exposure (light intensity 33,000 lux) had little effect on saclipin degradation. The average summer daytime sunlight intensity at the Earth's surface ranges from 32,000 lux to 100,000 lux. Therefore, saclipin may be useful as a sunscreen even during the summer daytime.

[0054] We investigated the effect of heat on the isomerization and stability of saclipin A and found that the cis-isomerization of saclipin A was promoted at higher temperatures (Fig. 3A and C). For example, the saclipin B ratio in the saclipin A extract was 7.2% before heat treatment. After 2 weeks of storage at 30°C, 50°C, and 70°C, the saclipin B ratio in the saclipin A extract increased to 8.0% ± 0.1%, 9.8% ± 0.4%, and 13.1% ± 0.2%, respectively. Saclipin did not decompose at any temperature during the 2-week storage period (Fig. 3B and D). This suggests that saclipin is highly stable against heat. These results suggest that skin quality improvement agents containing saclipin as an active ingredient can be stored for long periods.

[0055] The isomerization rate of saclipin A to saclipin B during heat treatment was comparable between the purified saclipin A and the saclipin A extract. The cis-isomerization rate constants (k) for the purified saclipin A at 30°C, 50°C, and 70°C were 6.4 × 10 -4 (day -1 ), 1.4×10 -3 (day -1 ), 1.4×10 -3 (day -1 The cis-isomerization rate constants (k) of the saclipin A extract at 30°C, 50°C, and 70°C were 4.7 × 10 -4 (day -1 ), 1.9×10 -3 (day -1 ), 4.3 × 10 -3 (day -1 Furthermore, the activation energies (Ea) for the isomerization from the trans isomer to the cis isomer of the purified saclipin A and the saclipin A extract were 45.7 kJ / mol and 47.9 kJ / mol, respectively.

[0056] Even when heated at 70°C, the reaction rate constant (k) was less than 1 / 10,000 of that obtained with light irradiation. This indicates that light irradiation is preferable to heat treatment for efficiently obtaining saclipin B from saclipin A.

[0057] Notably, the effects of light irradiation and heat treatment were comparable and very similar for the purified saclipin A product and the saclipin A extract. Considering the use of saclipin as a skin-improving agent, this suggests that the cyanobacterial extract can be used directly as a saclipin source, omitting the purification step.

[0058] 3. Experiment 3 (Singlet oxygen quenching activity) (1) Singlet oxygen quenching activity measurement Singlet oxygen quenching activity tests were performed using purified saclipin A and saclipin B. The tests were performed using the Antioxidant Capacity Assay Kit for Singlet Oxygen (SakuLab Science, Cat. No. SL-2010) in ethanol as the solvent. The saclipin concentrations for each sample were 0 mM, 0.008 mM, 0.04 mM, 0.2 mM, 1 mM, and 5 mM. Gallic acid, the target antioxidant, was used as a control.

[0059] (2) Results of Experiment 3 (Singlet oxygen quenching activity) The results of Experiment 3 are shown in Figure 4. The horizontal axis of the graph in Figure 4 represents the concentration (mM) of saclipin A or saclipin B. At each concentration, the dark graph on the left represents the results for saclipin A, and the light graph on the right represents the results for saclipin B. The vertical axis represents the singlet oxygen quenching rate (%).

[0060] As shown in Figure 4, both purified saclipin A and purified saclipin B exhibited singlet oxygen quenching activity. The IC50 values ​​for saclipin A and saclipin B were 1.2 mM and 2.07 mM, respectively. The IC50 values ​​for saclipin A and saclipin B were lower than the IC50 value of 5.26 mM for gallic acid. Singlet oxygen quenching activity generally depends on the number of conjugated double bonds, with trans isomers reported to have higher quenching activity than cis isomers. Similarly, in the case of saclipin, the trans isomer was found to exhibit higher singlet oxygen quenching activity than the cis isomer.

[0061] 4. Experiment 4 (Elastase inhibitory activity) (1) Elastase inhibitory activity test The elastase activity of saclipin was evaluated using N-methoxysuccinyl-Ala-Ala-Pro-Val-MCA as a substrate as follows.

[0062] Using ethanol as a solvent, test samples were prepared with saclipin concentrations of 0 μM, 0.8 μM, 1.6 μM, 3.1 μM, 6.3 μM, 12.5 μM, 25.0 μM, and 50.0 μM. A 1% ethanol solution was used as a control.

[0063] A 96-well plate was charged with 25 μL of test product or control solution, 25 μL of 10 mU / mL elastase (Sigma-Aldrich) solution, and 50 μL of 50 μM N-methoxysuccinyl-Ala-Ala-Pro-Val-MCA (Peptide Institute) solution. The samples were diluted with ethanol and further diluted 100-fold with water to the corresponding concentrations. Elastase and substrate were dissolved in 100 mM Tris-HCl (pH 8.0). The plate was shaken at 270 rpm for 10 seconds to mix the solutions, and the fluorescence intensity (Ex / Em: 360 / 465 nm) was measured immediately after the reaction (time 0) using a microplate reader. The solutions were then incubated at 37°C for 60 minutes, and the fluorescence intensity (Ex / Em: 360 / 465 nm) was measured. Elastase activity was calculated using the following formula: Elastase activity rate (%) = (S 60-S0) / (C 60 -C0) x 100 C0: Fluorescence intensity immediately after the control reaction C 60 : Fluorescence intensity of control after 60 minutes S0: Fluorescence intensity immediately after reaction of the test product S 60 : Fluorescence intensity of the test product after 60 minutes

[0064] (2) Results of Experiment 4 (Elastase inhibitory activity) The results of Experiment 4 are shown in Figures 5A and 5C. The horizontal axis of the graphs in Figures 5A and 5C shows the concentration (µM) of saclipin A or saclipin B. At each concentration, the dark-colored graph on the left shows the results for saclipin A, and the light-colored graph on the right shows the results for saclipin B. The vertical axis shows elastase activity (%).

[0065] As shown in Figure 5A, purified saclipin A and purified saclipin B were found to have potent elastase inhibitory effects. The inhibitory activities of saclipin A and B were roughly equivalent, with both showing an inhibition rate of 70% or more at a concentration of 50 μM. As shown in Figure 5C, the saclipin A and saclipin B extracts exhibited even stronger inhibitory activity than the purified products, completely inhibiting elastase activity at 12.5 μM. This suggests that the Aphanothece saclipin extract contains active ingredients other than saclipin. Considering that the purified product exhibited approximately 35% inhibitory activity at a concentration of 0.8 μM, while the inhibitory activity of the extract increased to approximately 60% at the same concentration, saclipin is thought to be responsible for the majority of the elastase inhibitory activity of the Aphanothece saclipin extract.

[0066] Inhibitors that work against serine proteases, including elastase, react with the P1 active site of the serine protease. In the case of β-lactam antibiotics such as penicillin, the carbonyl group of the β-lactam ring in the structure reacts with the active site, cleaving the β-lactam ring and forming a stable ester bond with the protease. The two carbonyl groups of saclipin A and saclipin B may play a role as serine protease inhibitors.

[0067] 5. Experiment 5 (Tyrosinase inhibitory activity) (1) Tyrosinase inhibitory activity test The tyrosinase inhibitory activity test evaluated the effect of saclipin on tyrosinase activity using 3,4-L-dihydroxyphenylalanine (L-DOPA) as a substrate.

[0068] Using ethanol as a solvent, test samples were prepared with saclipin concentrations of 0 μM, 0.8 μM, 1.6 μM, 3.1 μM, 6.3 μM, 12.5 μM, 25.0 μM, and 50.0 μM. A 1% ethanol solution was used as a control.

[0069] 25 μL of test product or control solution and 25 μL of 80 U / mL tyrosinase (Sigma-Aldrich) solution were added to a 96-well plate. Samples were diluted with ethanol and then further diluted 100-fold with water. 100 mM phosphate buffer (pH 6.8) was used as a tyrosinase blank. After incubation at 23°C for 3 minutes, 50 μL of 5 mM L-DOPA (FUJIFILM Wako Pure Chemical) solution was added. The plate was shaken at 270 rpm for 10 seconds to mix the solution, and the absorbance at 490 nm before incubation (time 0) was measured. The solution was then incubated at 23°C for 10 minutes, and the absorbance at 490 nm was measured. Tyrosinase activity was calculated using the following formula: Tyrosinase activity rate (%) ={(As 10 -Ab 10 )-(As0-Ab0)} / (Ac 10 -Ac0)×100 Ab0: blank absorbance before incubation Ab 10 : Blank absorbance after incubation Ac0: absorbance of control before incubation Ac 10 : Absorbance of control after incubation As0: absorbance of the test product before incubation As 10: Absorbance of the test product after incubation

[0070] (2) Results of Experiment 5 (Tyrosinase inhibitory activity) The results of Experiment 5 are shown in Figures 5B and 5D. The horizontal axis of the graphs in Figures 5B and 5D indicates the concentration (µM) of saclipin A or saclipin B. At each concentration, the dark-colored graph on the left shows the results for saclipin A, and the light-colored graph on the right shows the results for saclipin B. The vertical axis indicates tyrosinase activity (%).

[0071] As shown in Figure 5B, both saclipin A and saclipin B exhibited inhibitory activity against tyrosinase. The inhibitory activity of saclipin B was higher than that of saclipin A. The mechanism of action of saclipin as a tyrosinase inhibitor is thought to be due to its antioxidant activity. Some tyrosinase inhibitors are known to be strong antioxidants, and as mentioned above, saclipin also exhibits antioxidant activity in terms of singlet oxygen quenching activity (Figure 4). Although there is a contradiction in that saclipin A has higher singlet oxygen quenching activity and saclipin B has higher tyrosinase inhibitory activity (Figure 4), previous studies have reported that saclipin B has higher free radical scavenging activity than saclipin A.

[0072] On the other hand, tyrosinase activity significantly increased with saclipin extract at concentrations above 12.5 μM (Figure 5D). This unexpected phenomenon when using extracts may be due to the presence of a tyrosinase activator or to the presence of compounds unsuitable for analysis. In the latter case, the absorption of pigments such as chlorophyll in the extract may overlap with the measured absorbance at 490 nm, and further investigation of the measurement method is required. Furthermore, considering the inhibitory effect on melanin production in mouse B16 melanoma cells (Figure 7E), which will be described later, it cannot be ruled out at this time that saclipin-containing extracts may inhibit tyrosinase activity even at high concentrations.

[0073] 6. Experiment 6 (cell activation, collagen production, hyaluronic acid production, melanin production inhibition, melanin precursor (DHICA) darkening inhibition) (1) Cell The cells used were human-derived dermal fibroblasts from the NB1RGB cell line and B16 mouse melanoma cells. (2) Culture medium The culture media for dermal fibroblasts and B16 mouse melanoma cells were Eagle's Minimal Essential Medium (EMEM, Cat. No. 051-07615, Wako, Japan) containing 10.0% (v / v) Fetal Bovine Serum FBS and 1.0% (v / v) antifungal agent (Antibiotic-Antimycotic 100X, Cat. No. 15240-062, Invitrogen, USA), and Dulbecco's Modified Eagle's Medium (DMEM). (3) Test item The sample was diluted with test medium to prepare three concentrations (1 μM, 5 μM, 20 μM) before use. As a control, test medium containing 1% ethanol solution was used. (4) Test operation (4-1) Cell viability test Dermal fibroblasts and B16 mouse melanoma cells were each 1.0 × 10 4 and 5.0 x 10 4 Cells were seeded into a 96-well plate at a density of 100 cells / well and cultured at 37°C and 5% CO2 for 24 hours. The medium was then removed, and 100 μL of medium containing the sample was added. After 48 hours of culture, the medium was removed, and the cells were washed with PBS(-). Next, 0.5 mg / mL (for dermal fibroblasts) or 0.25 mg / mL (for B16 melanoma) 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was added to the wells, and the cells were cultured at 37°C for 2 hours (for dermal fibroblasts) or 1 hour (for B16 melanoma). After removing the MTT solution and washing with PBS(-), 200 μL of 2-propanol was added, and the absorbance at 570 nm was measured. Cell viability was calculated based on a control absorbance of 100%.

[0074] (4-2) Collagen and hyaluronic acid production promotion test in dermal fibroblasts The test product was diluted in EMEM medium containing 0.5% FBS. EMEM medium containing 0.5% FBS was used as a control medium. Dermal fibroblasts were cultured in a 96-well plate at 1.0 × 10 4 The cells were seeded at a density of 100 cells / well and cultured at 37°C and 5% CO2 for 24 hours. After removing the medium, 100 μL of the test product or control solution was added. After 48 hours of incubation, the supernatant medium was collected and stored at -80°C.

[0075] The contents of collagen and hyaluronic acid in the collected supernatant were measured by direct ELISA and sandwich ELISA, respectively. For collagen quantification, the collected medium was diluted 4-fold with PBS(-) and 100 μL of each was added to a high-binding 96-well plate. After overnight incubation at 4°C, the supernatant was removed, and the plate was washed with 200 μL of PBS(-) containing 0.05% Tween-20 (PBST). 150 μL of 1% bovine serum albumin (BSA) solution was added and incubated at 37°C for 1 hour. The BSA solution was removed, and the plate was washed with 200 μL of PBST. 100 μL of a 100 ng / mL biotin-labeled collagen type I antibody (Rockland) solution prepared in PBS(-) containing 0.5% BSA was added, and the plate was incubated at 37°C for 1 hour. The antibody solution was then removed, the cells were washed with PBST, 100 μL of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) solution was added, and the absorbance at 405 nm was measured. The absorbance of the control group was set at 100%, and the collagen production rate of the test product was calculated.

[0076] To quantify hyaluronic acid, a hyaluronic acid-binding protein (HABP) solution prepared in PBS(-) was added to a high-adsorption 96-well plate. After overnight incubation at 4°C, the supernatant was removed, the plate was washed with 200 μL of PBST, and 150 μL of 1% BSA solution was added and incubated at 37°C for 1 hour. The BSA solution was removed, the plate was washed with 200 μL of PBST, and 100 μL of the collected supernatant was diluted. A 100-fold dilution with PBS(-) was added and incubated at room temperature for 1 hour. The culture supernatant was removed, the plate was washed with PBST, and 100 μL of biotin-labeled HABP solution was added and incubated overnight at 4°C. The biotin-labeled HABP solution was removed, the plate was washed with 200 μL of PBST, and 100 μL of ABTS solution was added. The absorbance at 405 nm was measured. The hyaluronic acid production rate of the test samples was calculated based on the absorbance of the control group, which was set at 100%.

[0077] (4-3) Saclipin-induced melanin production inhibition in B16 mouse melanoma cells The test product was diluted in DMEM medium containing test medium, 100 nM α-melanocyte stimulating hormone (α-MSH, Sigma-Aldrich), and 100 μM theophylline (Sigma-Aldrich). Test medium was used as a control solution. B16 mouse melanoma cells were cultured in a 96-well plate at 1.0 × 10 4 The cells were seeded at a density of 1000 cells / well and cultured at 37°C and 5% CO for 24 hours. After that, the medium was removed, and 100 μL of the test product or control solution was added.

[0078] After 72 hours of incubation, each well was washed with PBS(-) preheated to 37°C. 120 μL of alamarBlue solution (Thermo Fisher Scientific) was added and incubated at 37°C for 1 hour. After incubation, 100 μL of alamarBlue solution was transferred to a new 96-well plate, and the absorbance at 570 nm and 650 nm was measured. The hyaluronic acid production rate of the test product was calculated based on the absorbance of the control group, which was set at 100%. Meanwhile, each well of the 96-well plate used for cell culture was washed with 200 μL of PBS(-). Next, 100 μL of 1M sodium hydroxide solution containing 10% dimethyl sulfoxide was added to each well, and the plate was incubated at 85°C for 10 minutes. The plate was shaken at 270 rpm for 60 seconds to mix the solution, and the absorbance at 405 nm was measured. The melanin production rate was calculated using the following formula: Melanin production rate (%) = SM / (S-SR) / CM / (C-CR) x 100 CM: Control OD405 C: Control OD570 CR: Control blank OD650 SM: OD405 of the test product S: OD570 of the test product SR: OD650 of the test product

[0079] (4-4) Inhibitory effect of saclipin melanin precursor (DHICA) on darkening in B16 mouse melanoma cells 100 μL of 20 μg / mL DHICA (Toronto Research Chemicals) and 100 μL of the test product or control solution were added to a 96-well plate. The test product was diluted with water. Water was used as the control solution. The plate was shaken at 270 rpm for 30 seconds to mix the solution, and the absorbance at 405 nm was measured. The plate was then placed in a Quartz reaction container (Ozawa Science) and irradiated for 30 minutes using a solar simulator (Suntest CPS+, Atlas). The plate was then shaken at 270 rpm for 30 seconds to mix the solution, and the absorbance at 405 nm was measured. The DHICA darkening rate was calculated using the following formula: DHICA blackening rate (%)=(S 30 -S0) / (C 30 -C0) x 100 C 30 : OD405 of control after irradiation C0: OD405 of control before irradiation S 30 : OD405 of the test item after irradiation S0: OD405 of the test item before irradiation

[0080] (5) Results of Experiment 6 (Collagen Production, Hyaluronic Acid Production) The results of Experiment 6 are shown in Figure 6. The horizontal axis of the graph in Figure 6 indicates the concentration (µM) of saclipin A or saclipin B. At each concentration, the dark-colored graph on the left shows the results for saclipin A, and the light-colored graph on the right shows the results for saclipin B. The vertical axes of Figures 6A and 6D indicate cell viability (%). The vertical axes of Figures 6B and 6E indicate collagen production (%). The vertical axes of Figures 6C and 6F indicate hyaluronic acid production (%).

[0081] The addition of purified saclipin A and purified saclipin B at a concentration of 20 μM was found to stimulate collagen production in dermal fibroblasts by approximately 10% (Fig. 6B). On the other hand, only purified saclipin B showed a significant stimulatory effect on hyaluronic acid production, increasing production by approximately 25% at 20 μM, whereas purified saclipin A showed no significant activity (Fig. 6C). It was also confirmed that the addition of saclipin up to a concentration of 20 μM did not affect the viability of dermal fibroblasts (Fig. 6A).

[0082] The extract, especially the saclipin B extract, was more effective in promoting collagen and hyaluronic acid production than the purified product. At a concentration of 20 μM, collagen and hyaluronic acid production increased 2-fold and 1.6-fold, respectively (Figures 6E and 6F). It should be noted that the saclipin extract affected the viability of dermal fibroblasts in a concentration-dependent manner (Figure 6D). Because the saclipin B extract can promote both collagen and hyaluronic acid production, it may be considered for use in cosmetics at a concentration range that does not affect cell viability.

[0083] (5) Results of Experiment 6 (inhibition of melanin production and darkening of melanin precursor (DHICA)) The results of Experiment 6 are shown in Figure 7. The horizontal axis of the graph in Figure 7 represents the concentration (µM) of saclipin A or saclipin B. At each concentration, the dark graph on the left represents the results for saclipin A, and the light graph on the right represents the results for saclipin B. The vertical axes of Figures 7A and 7D represent cell viability (%). The vertical axes of Figures 7B and 7E represent melanin production (%). The vertical axes of Figures 7C and 7F represent the melanization rate (%) of DHICA.

[0084] It was confirmed that neither purified saclipin A nor purified saclipin B had a significant adverse effect on the cell viability of B16 mouse melanoma cells (Figure 7A). As shown in Figure 7B, saclipin A and saclipin B inhibited melanin production in a dose-dependent manner. Saclipin A and B showed similar effects, inhibiting melanin production by approximately 10% at a concentration of 20 μM. When saclipin A was added at 1 μM, melanin production was irregularly promoted, but the significance of this result is unknown.

[0085] Similar experiments were performed using saclipin A extract and saclipin B extract, which showed higher melanin production inhibitory activity than the purified extract (Figure 7E). The activity of the saclipin B extract was relatively high, demonstrating 10% inhibitory activity at a concentration of 1 μM. At this concentration, the saclipin extract did not affect cell viability (Figure 7D). Furthermore, as shown in Figures 7C and 7F, purified saclipin did not inhibit DHICA-induced darkening, whereas the saclipin extract inhibited DHICA-induced darkening at a concentration of 5 μM. The saclipin A extract and saclipin B extract inhibited DHICA-induced darkening by approximately 21% and 16%, respectively. Considering the inhibition of DHICA-induced darkening at specific concentrations (Figure 7F), saclipin-containing extracts may be effective in whitening skin by suppressing the formation of dark spots and dullness.

[0086] 6. Effects of the Example This example demonstrates that a useful skin quality improving agent can be provided using Compound S as an active ingredient.

[0087] The present disclosure is not limited to the above-described embodiments, and various modifications and variations are possible within the scope of the claims of the present disclosure.

Claims

1. A skin quality improving agent containing, as an active ingredient, one or more compounds selected from the group consisting of a compound represented by the following formula (1), a compound represented by the following formula (2), and derivatives thereof: 【Chemistry 1】 【Chemistry 2】

2. 2. The skin quality improving agent according to claim 1, wherein the total amount of the compound represented by formula (1) and its derivatives is 20% by mass or more, when the total amount of the one or more compounds is 100% by mass.

3. The skin quality improving agent according to claim 1 or 2, which is used to inhibit skin aging.

4. The skin quality improving agent according to claim 1 or 2, which is used for whitening.

5. The skin quality improving agent according to claim 1 or 2, which is an external skin preparation or a cosmetic.

6. The skin quality improving agent according to claim 1 or 2, which is an oral agent.

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