A drug that suppresses mitochondrial damage caused by blue light.
The peony and quince plant extracts, optionally combined with phellodendron bark and citrus peel, address mitochondrial damage from blue light, enhancing skin and cell function by preserving mitochondrial integrity.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- CLUB COSMETICS
- Filing Date
- 2022-01-18
- Publication Date
- 2026-06-19
AI Technical Summary
Blue light emitted from devices such as smartphones causes mitochondrial damage in cells, leading to skin problems by increasing singlet oxygen, damaging mitochondrial membranes, and reducing ATP production, which affects skin and cell function.
A blue light-induced mitochondrial damage inhibitor containing extracts from the root of the peony plant (Paeonia lactiflora) and the fruit of the quince plant (Cinnamomum cuspidatum), along with optional extracts from phellodendron bark and citrus peel, suppresses mitochondrial damage by applying them as a cosmetic or topical skin preparation.
The inhibitor effectively suppresses mitochondrial damage caused by blue light, improving skin and cell function by maintaining mitochondrial quantity and membrane potential.
Smart Images
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Abstract
Description
Technical Field
[0001] The present invention relates to an inhibitor for suppressing mitochondrial damage by blue light.
Background Art
[0002] Mitochondria are intracellular organelles responsible for the production of ATP, which is the energy in the living body. In addition, they are important organs for maintaining cell homeostasis, involved in regulating oxidative stress, calcium concentration, controlling cell death, and metabolizing sugars, fatty acids, and amino acids. Mitochondria have two membranes, an outer membrane and an inner membrane, and the region surrounded by the inner membrane is called the matrix. In order to produce ATP, mitochondria form a hydrogen ion concentration gradient in the intermembrane space between the outer and inner membranes, generating a potential difference across the inner and outer membranes of mitochondria. Subsequently, ATP synthase on the inner membrane of mitochondria utilizes the potential difference across the inner and outer membranes of mitochondria to take hydrogen ions from the intermembrane space into the matrix and produce ATP.
[0003] In recent years, it has been reported that blue light emitted from LEDs used in smartphones and other devices may impair the function of skin and cells, potentially causing skin problems (see, for example, Joerg Liebmann et al., "Blue-Light Irradiation Regulates Proliferation and Differentiation in Human Skin Cells," The Journal of Investigative Dermatology, 130(1), 259-269, 2010 (Non-Patent Literature 1)). Blue light is visible light that can be seen by the human eye, and refers to light with a wavelength of 400nm to 500nm. Skin damage caused by blue light occurs when the amount of singlet oxygen increases in the mitochondria of cells (see, for example, Yuya Nakashima et al., "Blue light-induced oxidative stress in live skin," Free Radical Biology and Medicine, 108, 300-310, 2017 (Non-Patent Literature 2)). The increase in mitochondrial singlet oxygen damages the mitochondrial inner and outer membranes and mitochondrial DNA. Furthermore, damaged mitochondria are broken down in the body, reducing the total amount of mitochondria and decreasing the amount of ATP produced by mitochondria (see, for example, Non-Patent Literature 2 mentioned above, Deirdre Edge et al., "FLUORESCENT LIGHT ENERGY: The Future for Treating Inflammatory Skin Conditions?", The Journal of Clinical and Aesthetic Dermatology, 12(5), E61-E68, 2019 (Non-Patent Literature 3), Kawai, Kazuaki et al., "8-OH-dG Production and Repair Enzyme Response due to Oxidative Stress", Environmental mutagen research communication, 26, 143-148, 2004 (Non-Patent Literature 4)).From this, it can be inferred that the decrease in the total number and function of mitochondria caused by blue light (mitochondrial damage) has various effects on the skin.
[0004] Therefore, agents that suppress mitochondrial damage caused by blue light are considered important for maintaining and improving skin and cell function. To date, bilberry extract has been reported as an agent that improves cell damage caused by blue light (see, for example, Japanese Patent Publication No. 2015-044773 (Patent Document 1)). [Prior art documents] [Patent Documents]
[0005] [Patent Document 1] Japanese Patent Publication No. 2015-044773 [Non-patent literature]
[0006] [Non-Patent Document 1] Joerg Liebmann et al., “Blue-Light Irradiation Regulates Proliferation and Differentiation in Human Skin Cells”, The Journal of Investigative Dermatology, 130(1), 259-269, 2010 [Non-Patent Document 2] Yuya Nakashima et al., “Blue light-induced oxidative stress in live skin”, Free Radical Biology and Medicine, 108, 300-310, 2017 [Non-Patent Document 3] Deirdre Edge et al., “FLUORESCENT LIGHT ENERGY: The Future for Treating Inflammatory Skin Conditions?”, The Journal of Clinical and Aesthetic Dermatology, 12(5), E61-E68, 2019 [Non-Patent Document 4] Kawai, K. et al., "Formation of 8-OH-dG due to oxidative stress and response of repair enzymes," Environmental mutagen research communication, 26, 143-148, 2004. [Overview of the Initiative] [Problems that the invention aims to solve]
[0007] The present invention was made to solve the above problems, and its objective is to provide an agent that suppresses mitochondrial damage caused by blue light. [Means for solving the problem]
[0008] The blue light-induced mitochondrial damage inhibitor of the present invention contains at least one of the following as an active ingredient: an extract from the root of the peony plant (Paeonia lactiflora) of the Paeoniaceae family and an extract from the fruit of the quince plant (Cinnamomum cuspidatum) of the Rosaceae family (Hereafter, the blue light-induced mitochondrial damage inhibitor containing at least one of the following as an active ingredient will be referred to as the "first inhibitor").
[0009] The first inhibitor of the present invention preferably contains an extract obtained from the roots of Paeonia japonica, a member of the Paeoniaceae family, at a concentration of 1.0E-02 to 1.0E+03 μg / mL. In this case, it is preferable to use a mixture of water and 1,3-butylene glycol as the extraction solvent.
[0010] The first inhibitor of the present invention preferably contains an extract obtained from the fruit of the quince of the Rosaceae family at a concentration of 1.0E-01 to 2.0E+03 μg / mL. In this case, it is preferable to use a mixture of water and 1,3-butylene glycol as the extraction solvent.
[0011] The first inhibitor of the present invention preferably contains an extract from the fruit of the quince of the Rosaceae family as an active ingredient, and further preferably contains at least one of an extract from the bark of the phellodendron tree of the Rutaceae family and an extract from the fruit peel of the mandarin orange of the Rutaceae family.
[0012] Furthermore, the first inhibitor of the present invention preferably contains an extract from the root of the peony of the Paeoniaceae family as an active ingredient, and more preferably contains at least one of an extract from the fruit of the quince of the Rosaceae family and an extract from sea lettuce of the Sea lettuce family.
[0013] The present invention also provides a blue light-induced mitochondrial damage inhibitor containing paeoniflorin at a concentration of 1.0E-03 to 3.0E+04 μg / mL as an active ingredient (hereinafter, the blue light-induced mitochondrial damage inhibitor containing paeoniflorin at a concentration of 1.0E-03 to 3.0E+04 μg / mL as an active ingredient will be referred to as the "second inhibitor").
[0014] The present invention also provides a blue light-induced mitochondrial damage inhibitor containing albiflorin at a concentration of 1.0E-04 to 3.0E+03 μg / mL as an active ingredient (hereinafter, the blue light-induced mitochondrial damage inhibitor containing albiflorin at a concentration of 1.0E-04 to 3.0E+03 μg / mL as an active ingredient will be referred to as the "third inhibitor").
[0015] The present invention further provides a blue light-induced mitochondrial damage inhibitor containing paeoniflorin at a concentration of 1.0E-03 to 1.0E-00 μg / mL and albiflorin at a concentration of 1.0E-04 to 1.0E-01 μg / mL as active ingredients (hereinafter, the blue light-induced mitochondrial damage inhibitor containing paeoniflorin at a concentration of 1.0E-03 to 1.0E-00 μg / mL and albiflorin at a concentration of 1.0E-04 to 1.0E-01 μg / mL as active ingredients will be referred to as the "fourth inhibitor"). [Effects of the Invention]
[0016] According to the present invention, it is possible to provide agents that suppress mitochondrial damage caused by blue light, cosmetics, and topical skin preparations. [Modes for carrying out the invention]
[0017] (First inhibitor) The first inhibitor of the present invention contains at least one of the following as an active ingredient: an extract from the root of the peony plant (Paeonia lactiflora pallas) of the Paeoniaceae family (peony extract) and an extract from the fruit of the quince plant (Pseudocydonia sinensis) of the Rosaceae family (quince extract).
[0018] In the first inhibitor of the present invention, the peony root extract and the quince extract can be obtained by a general extraction method, for example, by immersing or heating under reflux with an extraction solvent, followed by filtration and concentration.
[0019] As the extraction solvent, any solvent generally used for extraction can be arbitrarily used, and either a polar solvent or a non-polar solvent can be used. For example, alcohols (including polyhydric alcohols) such as water, methanol, ethanol, propanol, butanol, propylene glycol, 1,3-butylene glycol, ketones such as acetone and methyl ethyl ketone, esters such as methyl acetate and ethyl acetate, chain and cyclic ethers such as tetrahydrofuran and diethyl ether, polyethers such as polyethylene glycol, hydrocarbons such as squalane, hexane, cyclohexane, petroleum ether, supercritical carbon dioxide, pyridines, fats and oils, waxes and other organic solvents such as other oils, and mixtures thereof can be mentioned. Preferably, water, alcohols, mixtures of alcohols and water, and hydrocarbons can be mentioned, and mixtures of alcohols and water and hydrocarbons are more preferable. Preferably, 1,3-butylene glycol or ethanol can be mentioned as the alcohols.
[0020] When extracting from the roots of peonies, considering the problems in case of residue, among those described above, it is preferable to use any one selected from water, polyhydric alcohol, and a mixture of water and polyhydric alcohol as the extraction solvent, more preferably to use a mixture of water and polyhydric alcohol as the extraction solvent, and particularly preferably to use a mixture of water and 1,3-butylene glycol (preferably a 20:80 to 80:20 mixture) as the extraction solvent.
[0021] Also, when extracting from the fruits of pomegranates, considering the problems in case of residue, among those described above, it is preferable to use any one selected from water, polyhydric alcohol, and a mixture of water and polyhydric alcohol as the extraction solvent, more preferably to use a mixture of water and polyhydric alcohol as the extraction solvent, and particularly preferably to use a mixture of water and 1,3-butylene glycol (preferably a 20:80 to 80:20 mixture) as the extraction solvent.
[0022] In the first inhibitor of the present invention, when the extract of Paeonia lactiflora is used as an active ingredient, the concentration of the extract of Paeonia lactiflora is not particularly limited, but it is preferably within the range of 1.0E-02 to 1.0E+03 μg / mL because it exhibits a more remarkable inhibitory effect on mitochondrial damage caused by blue light.
[0023] In the first inhibitor of the present invention, when the extract of Paeonia lactiflora is used as an active ingredient, it is preferably further contained with at least one of the extract extracted from the fruit of Chaenomeles japonica of the Rosaceae family and the extract extracted from Endocladiaceae of the family Endocladiaceae (Endocladiaceae extract) (see Experimental Example 2 described later).
[0024] When the extract of Paeonia lactiflora is used as an active ingredient and further contains the extract of Chaenomeles japonica, the concentration of the extract of Chaenomeles japonica is not particularly limited, but it is preferably within the range of 1.0E-01 to 3.0E+01 μg / mL because it exhibits a more remarkable inhibitory effect on mitochondrial damage caused by blue light.
[0025] When the extract of Paeonia lactiflora is used as an active ingredient and further contains the extract of Endocladiaceae, the concentration of the extract of Endocladiaceae is not particularly limited, but it is preferably within the range of 1.0E-01 to 1.0E+03 μg / mL because it exhibits a more remarkable inhibitory effect on mitochondrial damage caused by blue light.
[0026] In the first inhibitor of the present invention, when the extract of Chaenomeles japonica is used as an active ingredient, the concentration of the extract of Chaenomeles japonica is not particularly limited, but it is preferably within the range of 1.0E-01 to 2.0E+03 μg / mL because it exhibits a more remarkable inhibitory effect on mitochondrial damage caused by blue light.
[0027] In the first inhibitor of the present invention, when quince extract is used as the active ingredient, it is preferable to further include at least one of the following: an extract from the bark of Phellodendron amurense ruprecht of the Rutaceae family (Phellodendron amurense extract) and an extract from the peel of Citrus tachibana 'Tanaka' of the Rutaceae family (Citrus tachibana peel extract) (see Experimental Example 2 described later).
[0028] When quince extract is used as the active ingredient and Phellodendron bark extract is further included, the concentration of Phellodendron bark extract is not particularly limited, but it is preferable that it be in the range of 1.0E-01 to 1.0E+03 μg / mL, as this exhibits a more pronounced effect in suppressing mitochondrial damage caused by blue light.
[0029] When quince extract is used as the active ingredient and citrus peel extract is further included, the concentration of the citrus peel extract is not particularly limited, but it is preferable that it be in the range of 1.0E-01 to 1.0E+03 μg / mL, as this exhibits a more pronounced effect in suppressing mitochondrial damage caused by blue light.
[0030] Furthermore, the extraction methods and solvents for the above-mentioned seaweed extract, Phellodendron bark extract, and Citrus unshiu peel extract are not particularly limited and can be the same as those for the peony extract and quince extract described above.
[0031] The first inhibitor of the present invention can be used as is, such as peony root extract or quince extract, but is usually used as part of a composition with various carriers, and can be provided as a cosmetic or topical skin preparation (pharmaceutical or quasi-drug). The present invention also provides a cosmetic or topical skin preparation containing the first inhibitor of the present invention. In the cosmetic or topical skin preparation of the present invention, the dosage form is not limited and any dosage form that can be applied to the skin is acceptable, such as liquid preparations, ointments, hard ointments, emulsions, lotions, and packs. The amount to be included is usually 1.0E-03% (w / w) or more, preferably 1.0E-02 to 2.0E+01% (w / w), in the formulation for peony extract, and usually 1.0E-03% (w / w) or more, preferably 1.0E-02 to 2.0E+01% (w / w), in the formulation for quince extract. Furthermore, the first inhibitor of the present invention can be used in combination with other ingredients that have other effects, such as moisturizers, whitening agents, and UV protection agents.
[0032] (Second inhibitor) The peony extract, which is included as one of the active ingredients in the first inhibitor described above, is thought to contain paeoniflorin as one of its components. As demonstrated in Experimental Example 1 described later, it was found that mitochondrial damage caused by blue light can be suppressed when paeoniflorin at a concentration of 1.0E-03 to 3.0E+04 μg / mL is included as an active ingredient. In other words, the second inhibitor of the present invention is characterized by containing paeoniflorin at a concentration of 1.0E-03 to 3.0E+04 μg / mL as an active ingredient.
[0033] The second inhibitor of the present invention can be used as paeoniflorin as is, but is usually used as part of a composition with various carriers, etc., and can be provided as a cosmetic or topical skin preparation (pharmaceutical, quasi-drug). The present invention also provides a cosmetic or topical skin preparation containing the second inhibitor of the present invention. In the cosmetic or topical skin preparation of the present invention, the dosage form is not limited, and any dosage form that can be applied to the skin is acceptable, such as a liquid, ointment, hard ointment, emulsion, lotion, or pack. The amount included is usually 5.0E-05% (w / w) or more in the preparation, preferably 5.0E-04 to 1.0E-02% (w / w). Furthermore, the second inhibitor of the present invention can be used in combination with other ingredients that have other effects, such as moisturizers, whitening agents, or UV protection agents.
[0034] (Third inhibitor) Furthermore, it is believed that albiflorin is included as one of the active ingredients in the first inhibitor described above. As demonstrated in Experimental Example 1 described later, it was found that mitochondrial damage caused by blue light can be suppressed when albiflorin at a concentration of 1.0E-04 to 3.0E+03 μg / mL is included as an active ingredient. In other words, the third inhibitor of the present invention is characterized by containing albiflorin at a concentration of 1.0E-04 to 3.0E+03 μg / mL as an active ingredient.
[0035] The third inhibitor of the present invention can be used as albiflorin as is, but is usually used as part of a composition with various carriers, etc., and can be provided as a cosmetic or topical skin preparation (pharmaceutical or quasi-drug). The present invention also provides a cosmetic or topical skin preparation containing the third inhibitor of the present invention. In the cosmetic or topical skin preparation of the present invention, the dosage form is not limited and any dosage form that can be applied to the skin is acceptable, such as liquid preparations, ointments, hard ointments, emulsions, lotions, and packs. The amount included is usually 5.0E-04% (w / w) or more in the preparation, preferably 5.0E-04% to 1.0E-03% (w / w). Furthermore, the third inhibitor of the present invention can be used in combination with other ingredients that have other effects, such as moisturizers, whitening agents, and UV protection agents.
[0036] (The fourth inhibitor) As demonstrated in Experimental Example 3 described later, the inventors have found that when both paeoniflorin and albiflorin are included as active ingredients, mitochondrial damage caused by blue light can be suppressed even at lower concentrations than the second and third inhibitors, respectively. That is, the fourth inhibitor of the present invention is characterized by containing paeoniflorin at a concentration of 1.0E-03 to 1.0E+00 μg / mL and albiflorin at a concentration of 1.0E-04 μg / mL to 1.0E-01 μg / mL as active ingredients.
[0037] The fourth inhibitor of the present invention can be used as paeoniflorin and albiflorin as they are, but is usually used as part of a composition with various carriers, etc., and can be provided as a cosmetic or topical skin preparation (pharmaceutical or quasi-drug). The present invention thus also provides a cosmetic or topical skin preparation containing the fourth inhibitor of the present invention. In the cosmetic or topical skin preparation of the present invention, the dosage form is not limited and any dosage form that can be applied to the skin is acceptable, such as liquid preparations, ointments, hard ointments, emulsions, lotions, and packs. The amount of paeoniflorin is usually 1.0E-05% (w / w) or more, preferably 5.0E-05 to 1.0E-03% (w / w), and the amount of albiflorin is usually 1.0E-06% (w / w) or more, preferably 5.0E-06 to 1.0E-04% (w / w). Furthermore, the fourth inhibitor of the present invention can be used in combination with other ingredients that have other effects, such as moisturizers, whitening agents, and UV protection agents.
[0038] The present invention will be further explained with experimental examples below, but the present invention is not limited to these.
[0039] <Experimental Example 1> To confirm the mitochondrial damage-suppressing effect of each individual sample, the samples listed in Table 1 were evaluated.
[0040] (Sample preparation) The fruit of the Rosaceae family quince was extracted using an aqueous solution of 1,3-butylene glycol as the extraction solvent. The quince extract was prepared using Dulbecco's Modified Eagle Medium (DMEM) to obtain a 90 μg / mL quince extract (Example 1) and a 170 μg / mL quince extract (Example 2).
[0041] The roots of the Paeonia japonica plant (a member of the Paeoniaceae family) were extracted using an aqueous solution of 1,3-butylene glycol as the extraction solvent. The peony extracts were prepared using DMEM medium to obtain 35 μg / mL peony extract (Example 3) and 70 μg / mL peony extract (Example 4).
[0042] Commercially available albiflorin was used. Albiflolin was prepared using dimethyl sulfoxide prepared in a 0.1% final concentration DMEM medium to obtain 0.3 μg / mL albiflorin (Example 5) and 3 μg / mL albiflorin (Example 6).
[0043] Commercially available paeoniflorin was used. Paeoniflorin was prepared using dimethyl sulfoxide prepared in a 0.1% final concentration DMEM medium to obtain 3 μg / mL paeoniflorin (Example 7) and 30 μg / mL paeoniflorin (Example 8).
[0044] Fibroblasts were seeded on chamber slides and cultured for 24 hours. Then, the samples from Examples 1-8 described above were added to DMEM medium and cultured. Subsequently, the cells were irradiated with blue light at 400 nm to 500 nm. After blue light irradiation, mitochondrial localization reagents and mitochondrial membrane potential reagents were added and stained. Then, the effect of blue light on suppressing mitochondrial damage was evaluated using mitochondrial quantity and mitochondrial membrane potential as indicators. Cells that were not irradiated with blue light were shielded from the blue light with aluminum foil and stained in the same manner.
[0045] For comparison, Comparative Example 1 involved samples that were not irradiated with blue light, while Comparative Example 2 involved samples that were irradiated with blue light but did not contain any of the samples from Examples 1-8. The results are shown in Table 1.
[0046] [Table 1]
[0047] Comparative Example 2, which was irradiated with blue light, showed a significantly lower mitochondrial volume and mitochondrial membrane potential compared to Comparative Example 1, which was not irradiated with blue light, confirming that mitochondrial damage occurred due to blue light. Next, the samples were evaluated, and it was found that quince extract (Examples 1 and 2), peony extract (Examples 3 and 4), albiflorin (Examples 5 and 6), and paeoniflorin (Examples 7 and 8) had the effect of improving the decrease in mitochondrial volume and mitochondrial membrane potential caused by blue light, suggesting that they have excellent mitochondrial damage suppression effects.
[0048] <Experimental Example 2> The inhibitory effect of inhibitors containing quince extract or peony extract as active ingredients on suppressing mitochondrial damage was evaluated in the same manner as in Experimental Example 1. Each inhibitor is shown in Table 2, and the results are shown in Table 3.
[0049] Phellodendron amurense bark, obtained by extracting it from the bark of Phellodendron amurense (a member of the Rutaceae family) using an aqueous 1,3-butylene glycol solution as the extraction solvent, was prepared using DMEM medium.
[0050] An extract of tangerine peel was prepared using DMEM medium, obtained by extracting from the pericarp of the citrus fruit (Tachibana orange) collected from the citrus family using an aqueous 1,3-butylene glycol solution as the extraction solvent.
[0051] An extract of seaweed (Sargassum fusiforme) was prepared using DMEM medium, obtained by extracting seaweed from collected seaweed using an aqueous 1,3-butylene glycol solution as the extraction solvent.
[0052] [Table 2]
[0053] [Table 3]
[0054] As shown in Table 3, Examples 9-12 showed an effect of improving the decrease in mitochondrial quantity and membrane potential caused by blue light, and were considered to have an excellent inhibitory effect on mitochondrial damage. Furthermore, Comparative Examples 3-7, which used each extract alone, did not show an inhibitory effect on mitochondrial damage, and it was found that the inhibitory effect on mitochondrial damage was improved by combining quince extract, peony extract, Phellodendron bark extract, citrus peel extract, or seaweed extract.
[0055] <Experimental Example 3> The inhibitory effect of various inhibitors on mitochondrial damage was evaluated by combining components of peony extract. The experiment was conducted in the same manner as in Experiment Example 1. Each inhibitor is shown in Table 4, and the results are shown in Table 5.
[0056] [Table 4]
[0057] [Table 5]
[0058] As shown in Table 5, Example 13 showed an effect of improving the decrease in mitochondrial quantity and membrane potential caused by blue light, and was considered to have an excellent effect in suppressing mitochondrial damage. Furthermore, Comparative Examples 8 and 9, which contained only low concentrations of each component, did not show any effect in suppressing mitochondrial damage, and it was found that the effect of suppressing mitochondrial damage was improved by combining low concentrations of albiflorin and paeoniflorin.
Claims
1. A blue light-induced mitochondrial damage inhibitor containing at least one of the following as an active ingredient: an extract from the root of the peony plant (Paeoniaceae) and an extract from the fruit of the quince plant (Rosaceae); When containing an extract from the roots of the peony plant (Paeoniaceae) as an active ingredient, the extract from the roots of the peony plant (Paeoniaceae) is contained at a concentration of 1.0E-02 to 1.0E+03 μg / mL, and further contains at least one of the extracts from the fruit of the quince plant (Rosaceae) and the seaweed (Sea lettuce) of the Seaweed family. A blue light-induced mitochondrial damage inhibitor that contains an extract from the fruit of the quince tree (Rosaceae family) as an active ingredient, and further contains an extract from the peel of the mandarin orange tree (Rutaceae family).
2. The inhibitor according to claim 1, wherein the extraction solvent is a mixture of water and 1,3-butylene glycol.
3. The inhibitor according to claim 1, wherein, when containing an extract from the fruit of the quince of the Rosaceae family as an active ingredient, the inhibitor contains an extract from the fruit of the quince of the Rosaceae family at a concentration of 1.0E-01 to 2.0E+03 μg / mL.
4. The inhibitor according to claim 3, wherein the extraction solvent is a mixture of water and 1,3-butylene glycol.