Lutein-containing composition

Abstract

This invention provides compositions for enhancing the beneficial physiological activity of lutein by combining it with other active ingredients, and a method for protecting the retina from reactive oxygen species. [Solution] A composition is provided containing lutein and one or more selected from the group consisting of (a) to (e) below: (a) At least one plant material selected from pomegranate, bacopa, and moringa; (b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; (c) β-caryophyllene or plasmalogen; (d) at least one vitamin selected from vitamin B2, vitamin B6, and vitamin B12; (e) At least one fatty acid selected from alpha-linolenic acid, caprylic acid, capric acid, linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid.

Description

Technical Field

[0001] The present invention relates to a lutein-containing composition. In particular, the present invention relates to a lutein-containing composition having an antioxidant effect.

Background Art

[0002] Lutein is one of the yellow pigments derived from carotenoids called xanthophylls. It is known to be contained in various foods, such as corn, fruits, and green vegetables. Also, lutein is present in the macula lutea of the retina, the lens, the skin, the breast, the large intestine, etc. in the human body.

[0003] Lutein is known to have various physiological activities, and therapeutic effects (Patent Document 1) and cognitive function improvement effects (Patent Document 2) on eye diseases such as age-related macular degeneration and nuclear cataract have been reported; at least some of them are said to be due to the antioxidant effect of lutein. For example, lutein is present in the macula lutea of the retina and the lens together with zeaxanthin, and is said to inactivate the reactive oxygen species generated in the eye.

[0004] Furthermore, it has also been reported that by combining (using in combination) lutein with other active ingredients, the retinal protection effect can be enhanced (Patent Document 3). That is, in Patent Document 3, oxidative stress is applied to human retinal pigment epithelial cells, and the antioxidant effect of the combination of lutein and other components is evaluated using the expression level of TGFβ1 (Transforming Growth Factor-beta 1) as an index.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Patent Document 3

[0006] Lutein has been shown to have various physiologically active effects, and attempts have been made to enhance these effects by combining lutein with other active ingredients. However, as lutein is attracting increasing attention as an active ingredient in health foods and other products, there is a need to further enhance its activity, and in particular, attempts are being made to increase lutein's antioxidant effect to obtain various beneficial biological activities.

[0007] Therefore, the present invention aims to enhance the beneficial physiological activity of lutein by combining it with other active ingredients. For example, physiological activity that is not sufficiently (or not at all) observed with lutein alone can be enhanced by combining it with other active ingredients. Furthermore, the present invention aims to obtain high antioxidant power by combining lutein with other ingredients. [Means for solving the problem]

[0008] In other words, the first aspect of the present invention relates to the lutein-containing composition shown below. [1] A composition containing lutein and one or more selected from the group consisting of (a) to (e) below: (a) At least one plant material selected from pomegranate, bacopa, and moringa; (b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; (c) β-caryophyllene or plasmalogen; (d) At least one vitamin selected from vitamin B2, vitamin B6, and vitamin B12; (e) At least one fatty acid selected from alpha-linolenic acid, caprylic acid, capric acid, linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid. [2] A composition containing lutein and one or more selected from the group consisting of (a) to (e') below: (a) At least one plant material selected from pomegranate, bacopa, and moringa; (b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; (c) β-caryophyllene or plasmalogen; (d) At least one vitamin selected from vitamin B2, vitamin B6, and vitamin B12; (e') At least one oil or fat selected from perilla oil, MCT oil, safflower oil, rice germ oil, flaxseed oil, and krill oil.

[0009] The present invention preferably relates to the following lutein-containing compositions. [3] The composition according to [1] or [2] above, which is for antioxidant purposes. [4] The antioxidant composition described in [3] above, for protection from reactive oxygen species. [5] A composition according to any one of [1] to [4] above, for retinal protection. [6] The retinal protective composition described in [5] above, for the purpose of protecting the retina from reactive oxygen species. [7] A composition according to any one of [1] to [6] above, for oral use. [8] Capsules, tablets, powders, granules, or liquids comprising the composition described in any of [1] to [7] above.

[0010] Furthermore, the present invention relates to the following method. [9] A method for protecting the retina from reactive oxygen species, characterized by using a composition containing lutein and one or more selected from the group consisting of (a) to (e) below: (a) At least one plant material selected from pomegranate, bacopa, and moringa; (b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; (c) β-caryophyllene or plasmalogen; (d) At least one kind of vitamins selected from vitamin B2, vitamin B6, and vitamin B12; (e) At least one kind of fatty acids selected from α-linolenic acid, caprylic acid, capric acid, linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid.

[10] A method for protecting the retina from reactive oxygen species, characterized by using a composition containing lutein and one or more selected from the group consisting of the following (a) to (e’): (a) At least one plant material selected from pomegranate, Bacopa monnieri, and Moringa oleifera; (b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; (c) β-caryophyllene or plasmalogen; (d) At least one kind of vitamins selected from vitamin B2, vitamin B6, and vitamin B12; (e’) At least one kind of oils and fats selected from sesame oil, MCT, safflower oil, rice bran oil, flaxseed oil, and krill oil.

[0011]

[11] A method for improving the antioxidant power of lutein, characterized by using one or more selected from the group consisting of the following (a) to (e): (a) At least one plant material selected from pomegranate, Bacopa monnieri, and Moringa oleifera; (b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; <00​​​​​​​​​​(b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; (c) β-carotene or plasmalogen; (d) At least one vitamin selected from vitamin B2, vitamin B6, and vitamin B12; (e’) At least one oil or fat selected from sesame oil, MCT, safflower oil, rice bran oil, linseed oil, and krill oil.

Advantages of the Invention

[0012] By combining lutein with other active ingredients, the present invention can obtain strong antioxidant power and exhibit retinal protection function and other physiological activities. For example, the antioxidant power that cannot be fully expressed by lutein alone (such as due to too low lutein concentration) can be enhanced by combining it with other active ingredients. Therefore, the lutein-containing composition of the present invention can maintain the functions of the eyes, etc., especially when orally ingested.

Brief Description of the Drawings

[0013] [Figure 1] It is a graph showing the relationship between the expression level (Y-axis) of the TGFβ1 gene in human retinal pigment epithelial cells and the amount of hydrogen peroxide added (X-axis: no addition (-), 100 μM, 500 μM, 1000 μM). [Figure 2A] It is a graph showing how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes with no component addition (control), lutein alone, pomegranate extract alone, and the combination of lutein and pomegranate extract. [Figure 2B] It is a graph showing how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes with no component addition (control), lutein alone, Bacopa extract alone, and the combination of lutein and Bacopa extract. [Figure 2C]This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, moringa extract alone, and a combination of lutein and moringa extract. [Figure 2D] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, rooibos extract alone, and a combination of lutein and rooibos extract. [Figure 2E] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, Rhodiola rosea extract alone, and a combination of lutein and Rhodiola rosea extract. [Figure 2F] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, passionflower extract alone, and a combination of lutein and passionflower extract. [Figure 2G] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, ginkgo extract alone, and a combination of lutein and ginkgo extract. [Figure 2H] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes with no added components (control), lutein alone, Astragalus membranaceus extract alone, and a combination of lutein and Astragalus membranaceus extract. [Figure 2I] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, elm tree extract alone, and a combination of lutein and elm tree extract. [Figure 2J] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, resveratrol alone, and a combination of lutein and resveratrol. [Figure 2K]This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, β-caryophyllene alone, and a combination of lutein and β-caryophyllene. [Figure 2L] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, vitamin B2 alone, and a combination of lutein and vitamin B2. [Figure 2M] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, vitamin B6 alone, and a combination of lutein and vitamin B6. [Figure 2N] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, vitamin B12 alone, and a combination of lutein and vitamin B12. [Figure 2O] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, perilla oil alone, and a combination of lutein and perilla oil. [Figure 2P] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, MCT alone, and a combination of lutein and MCT. [Figure 2Q] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, safflower oil alone, and a combination of lutein and safflower oil. [Figure 2R] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, rice germ oil alone, and a combination of lutein and rice germ oil. [Figure 2S]This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, flaxseed oil alone, and a combination of lutein and flaxseed oil. [Figure 2T] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, plasmalogen alone, and a combination of lutein and plasmalogen. [Figure 2U] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes under the following conditions: no additives (control), lutein alone, krill oil alone, and a combination of lutein and krill oil. [Figure 2V] This graph shows how the expression level of the TGFβ1 gene in human retinal pigment epithelial cells changes with lutein alone, olive oil alone, and a combination of lutein and olive oil. [Modes for carrying out the invention]

[0014] [1. Lutein-containing composition] The lutein-containing composition of the present invention comprises lutein along with certain other active ingredients, which preferably enhance the antioxidant effect of lutein and more preferably enhance its retinal protective function.

[0015] [1-1. Lutein] Lutein is a type of carotenoid found in the leaves, flowers, fruits, etc. of plants; the lutein contained in the lutein-containing composition of the present invention may be plant-derived lutein or lutein produced by chemical synthesis.

[0016] Plant-derived lutein can be, for example, lutein derived from marigolds, which are rich in lutein. Marigolds are a type of plant belonging to the Asteraceae family, and marigold extracts obtained from marigolds (preferably marigold petals) contain lutein. Generally, lutein derived from marigolds can be obtained by extracting it from dried marigold petals with an organic solvent such as hexane, removing the organic solvent from the extract, hydrolyzing it (lutein may exist as a lutein ester in plants), and then purifying and crystallizing it. The purified and crystallized product contains approximately 20% lutein. Such marigold-derived lutein is commercially available and can be obtained as Lutemax 2020 (Unifoodia Co., Ltd.), FloraGLO® Lutein 20% SAF (DSM), Lutein Hi-Fil 20 (Omnica Co., Ltd.), etc. The lutein-containing composition may also be an ester of lutein.

[0017] The lutein content in a lutein-containing composition is preferably set according to the daily intake or dosage of lutein. For example, the daily intake or dosage of lutein is preferably 1 mg or more, more preferably 5 mg or more, and even more preferably 10 mg or more; on the other hand, it is preferably 2 g or less, more preferably 1 g or less, and even more preferably 500 mg or less.

[0018] [1-2. Specific other active ingredients] The lutein-containing composition of the present invention contains components (specific other active ingredients) that can enhance the biological functions of lutein. These specific other active ingredients can be broadly classified into plant materials, polyphenols, β-caryophyllene, plasmalogens, vitamins, and fatty acids; or they can be broadly classified into plant materials, polyphenols, β-caryophyllene, plasmalogens, vitamins, and oils and fats. When combined with lutein, these can reduce the gene expression level of TGFβ1 (Transforming growth factor-β1) in retinal pigment epithelial cells. This suggests that oxidative stress on retinal pigment epithelial cells is reduced, meaning that the combination of lutein and other active ingredients exhibits antioxidant activity.

[0019] [1-2-1. Plant Materials] The plant material contained in the lutein-containing composition of the present invention is at least one plant material selected from pomegranate, bacopa, and moringa; typically, it is an extract of these plant materials.

[0020] Pomegranates belong to the genus Punicacia in the family Lythraceae, and their extracts are reported to contain polyphenols such as anthocyanins and ellagic acid. Pomegranate extract is usually extracted from the fruit or seeds. Pomegranate extract is available on the market as dried pomegranate seed extract (ASK Pharmaceutical Co., Ltd.), pomegranate extract powder 10 (Ikeda Sugar Refining Co., Ltd.), Pomanox P30 (NC Corporation), etc.

[0021] Bacopa is an evergreen perennial herb belonging to the genus Sutera or Bacopa, and its extract has been reported to contain bacoside, a type of saponin. Bacopa extract is usually extracted from its leaves. Bacopa extract is available on the market as Bacopa extract powder (Nippon Shinyaku Co., Ltd.), Bacopa monnieri extract powder (Organo Food Tech Co., Ltd.), etc.

[0022] Moringa, also known as horseradish tree, is a plant belonging to the Moringa genus. Its extract is reported to contain not only essential amino acids but also numerous non-essential amino acids. Moringa extract can be obtained not only from the seeds but also from the leaves, stems, and trunk. Moringa extract is available on the market as Moringa Extract S (Taiyo Kagaku Co., Ltd.), etc.

[0023] [1-2-2. Polyphenols] The polyphenols contained in the lutein-containing composition of the present invention are at least one functional component selected from flavonoids, curcumin, and resveratrol.

[0024] Flavonoids, which are polyphenols, are compounds that have a diphenylpropane structure in which two phenyl groups are linked by three carbon atoms. Flavonoids can be broadly classified into flavonols, flavanones, flavones, catechins, isoflavones, anthocyanidins, chalcones, biflavones, ginknetin, birovetin, polymethoxyflavones, etc.

[0025] Examples of flavonols include rutin, quercetin, myricetin, myricitrin, and quercitrin. Examples of flavanones include naringenin, hesperetin, flavanone, flavanonol, naringin, hesperidin, and liquiriti. Examples of flavones include apigenin, luteolin, flavone, apiin, trindin, and forznerin. Examples of catechins include catechin, gallocatechin, epicatechin, and epigallocatechin. Examples of isoflavones include daidzin, genistin, glycitin, daidzein, genistein, and glycitein. Examples of anthocyanidins include cyanidin, delphinidin, and anthocyanin. The type of flavonol contained in the lutein-containing composition of the present invention is not particularly limited as long as it achieves the effects of the present invention.

[0026] Flavonoids may be synthetic or extracted from plants containing flavonoids. While not limited to flavonoid-containing plants, examples include rooibos, rhodiola rosea, passionflower (Japanese name: Chabotokeisou), ginkgo, and Astragalus sinicus.

[0027] Rooibos is a species of the Aspalathus genus in the legume subfamily. Its extract is reported to contain flavonols and flavones, including dihydrochalcone, vitexin, luteolin, quercetin, and eriodictyol-6-C-glucoside. Rooibos extract is usually extracted from its leaves. Rooibos extract is available on the market as Pure Rooibos Extract L (Maruzen Pharmaceutical Co., Ltd.) and Green Rooibos Extract (Tama Biochemical Co., Ltd.), among others.

[0028] Rhodiola rosea is a perennial herb belonging to the Apocynaceae family, and its extract has been reported to contain flavonoids such as hyperoside and isoquercitrin. Rhodiola rosea extract is usually extracted from its leaves. Rhodiola rosea extract is available on the market as Benetron (Tokiwa Botanical Chemical Research Institute Co., Ltd.), among others.

[0029] Passionflower (Japanese name: Chabotokeisou) is a perennial vine plant, and its extract has been reported to contain alkaloids as well as flavonoids. Passionflower extract is usually extracted from its fruit, stems, leaves, and flowers. Passionflower extract is available on the market as Chabotokeisou Extract (Kenko Tsusho Co., Ltd.), Passionflower Extract-P (Oryza Oil & Fat Chemical Co., Ltd.), etc.

[0030] Ginkgo biloba is a deciduous tree belonging to the gymnosperms, and its extracts have been reported to contain flavonoids as well as ginkgolides. Ginkgo extract is usually extracted from its leaves. Ginkgo extract is available on the market as Ginkgo Leaf Extract Powder MF (Maruzen Pharmaceutical Co., Ltd.), Ginkgolon-24J (Tokiwa Botanical Chemical Research Institute Co., Ltd.), Ginkgo Extract-F (Tama Biochemical Co., Ltd.), etc.

[0031] Astragalus sinicus is a perennial plant belonging to the legume family, and its extract has been reported to contain flavonoids and other compounds. Astragalus sinicus extract is usually extracted from its seeds. Astragalus sinicus extract is available on the market as Astragalus sinicus dry extract F (Maruzen Pharmaceutical Co., Ltd.), etc.

[0032] Curcumin, a polyphenol, is a pigment component classified as a curcuminoid and is said to have antioxidant and liver function-improving effects. Curcumin may be a synthetic product or extracted from plants that contain curcumin. There are no particular limitations on plants that contain curcumin, but examples include the mimosa tree (Albizia julibrissin). The mimosa tree is a deciduous tree belonging to the genus Albizia in the subfamily Mimosoideae of the legume family, and its extract has been reported to contain curcumin along with betaine, chlorgenic acid, and vitamin C. Mimosa tree extract is usually extracted from its bark. Mimosa tree extract is available on the market as Nemunos (Combi Corporation), etc.

[0033] Resveratrol, a polyphenol, is said to have antioxidant properties. Resveratrol is found in red wine, as well as in the seeds and skins of black grapes and the thin skin of peanuts. Resveratrol exists in cis and trans forms, but the trans form is preferred. Resveratrol may also be in the form of a dimer or glycoside. Resveratrol is available on the market as Red Wine Extract R5 (Anti-Aging Pro Co., Ltd.), VINEATROL® 20M (Sunbright Co., Ltd.), etc. [ka]

[0034] [1-2-3. β-caryophyllene, plasmalogen] β-Caryophyllene, represented by the structural formula shown below, is a type of substance called a terpene and is often found in the essential oils of plants. Examples of plants containing β-caryophyllene include clove (Syzygium aromaticum), copaiba (Copaifera longsdorffii), cananga (Cananga odorata), cangelana (Cabralea cangerana Saldanha), hemp (Cannabis sativa), and pepper (Pipernigrum). β-Caryophyllene is available on the market as Relaxphyton (Inabata International Corporation), among other products. [ka]

[0035] Plasmalogens are a type of phospholipid (glycerophospholipid) that are present in the bodies of humans and mammals. There are no particular restrictions on the source of plasmalogens; they can originate from sources such as chicken breast, pig brains, scallops, and sea squirts. Plasmalogens are available on the market, such as sea squirt-derived plasmalogens (Nippon Yakuhin Co., Ltd.).

[0036] [1-2-4. Vitamins] Vitamins are at least one of the following: vitamin B2, vitamin B6, and vitamin B12. These vitamins are also available from the market.

[0037] Vitamin B2 refers to vitamin B2 (riboflavin), its derivatives, and salts thereof. The type of vitamin B2 included in the lutein-containing composition of the present invention is not particularly limited, as long as it is suitable for incorporation into food. Examples of salts of vitamin B2 and its derivatives include inorganic salts such as hydrochloride and nitrate. These vitamin B2s may be used individually or in combination of two or more.

[0038] Vitamin B6 refers to vitamin B6 (pyridoxine), its derivatives, and salts thereof. The type of vitamin B6 contained in the lutein-containing composition of the present invention is not particularly limited, as long as it is suitable for incorporation into food. Examples of salts of vitamin B6 and its derivatives include inorganic salts such as hydrochloride salts. These vitamin B6s may be used individually or in combination of two or more types.

[0039] Vitamin B12 refers to vitamin B12 (cyanocobalamin), its derivatives, and salts thereof. The type of vitamin B12 included in the lutein-containing composition of the present invention is not particularly limited, as long as it is suitable for incorporation into food. Examples of salts of vitamin B12 and its derivatives include inorganic salts such as hydrochloride and nitrate. These vitamin B12s may be used individually or in combination of two or more types.

[0040] [1-2-5. Fatty acids or oils and fats] The fatty acids contained in the lutein-containing composition of the present invention are at least one component selected from α-linolenic acid, caprylic acid, capric acid, linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid. Furthermore, the oils and fats contained in the lutein-containing composition of the present invention are at least one component selected from perilla oil, MCT, safflower oil, rice germ oil, flaxseed oil, and krill oil.

[0041] Alpha-linolenic acid is a polyunsaturated fatty acid with 18 carbon atoms and 3 double bonds. Caprylic acid is a saturated fatty acid with 8 carbon atoms. Capric acid is a saturated fatty acid with 10 prime bonds. Linoleic acid is a polyunsaturated fatty acid with 18 carbon atoms and 2 double bonds. Docosahexaenoic acid is a polyunsaturated fatty acid with 22 carbon atoms and 6 double bonds. Eicosapentaenoic acid is a polyunsaturated fatty acid with 20 carbon atoms and 5 double bonds.

[0042] The fatty acids contained in the lutein-containing composition of the present invention may be purified, or oils and fats containing fatty acids may be used.

[0043] Oils containing alpha-linolenic acid are not particularly limited, but include perilla oil, flaxseed oil, chia seed oil, and sacha inchi oil, with perilla oil and flaxseed oil being preferred. Perilla oil is a vegetable oil derived from the seeds (fruits) of the perilla plant, an annual herb of the Lamiaceae family. Perilla oil is available on the market as shiso oil (Oryza Oil & Fat Chemical Co., Ltd.) and shiso oil (Nippon Oil Corporation). Flaxseed oil is an edible oil obtained from the seeds of mature flax. Flaxseed oil is available on the market as flaxseed oil (Summit Oil Co., Ltd.) and organic flaxseed oil (CANA Co., Ltd.).

[0044] Caprylic acid and capric acid are types of MCTs. MCT stands for Medium Chain Triglyceride, a plant component found in the seeds of palm trees such as coconuts and palm fruit. MCTs are available on the market as Coconad ML (Kao Corporation) and Schole 64G (Nisshin Oillio Group Ltd.).

[0045] Oils containing linoleic acid are not particularly limited, but include safflower oil, rice germ oil, corn oil, and soybean oil, with safflower oil and rice germ oil being preferred. Safflower oil is extracted from the seeds of safflower, an annual plant belonging to the genus Carthamus in the Asteraceae family. Safflower oil is available on the market as safflower salad oil (Nisshin Oillio Group Ltd.) and safflower salad oil (Summit Oil Co., Ltd.). Rice germ oil is extracted from the germ of rice and is reported to contain "γ-oryzanol". Rice germ oil is available on the market as rice germ oil (Tsukuno Foods Industry Co., Ltd.) and Oryza rice oil (Oryza Oil & Fat Chemical Co., Ltd.).

[0046] The oils and fats containing docosahexaenoic acid or eicosapentaenoic acid are not particularly limited, but include fish oil and krill oil, with krill oil being preferred. Krill oil is an edible oil extracted and refined from Antarctic krill, a type of zooplankton. Krill oil has been reported to contain omega-3 unsaturated fatty acids and astaxanthin. Krill oil is available on the market as Superba 2 Krill Oil (Aker Biomarine Antarctic AS), etc.

[0047] [1-2-6. Content of specific other active ingredients] In the lutein-containing composition of the present invention, the mass ratio of lutein to specific other active ingredients should be set to enhance the physiological activity of lutein, including its antioxidant effect, but the following is a guideline.

[0048] When the amount of lutein contained in the lutein-containing composition is 1 part by mass: Pomegranate extract is preferably 0.01 to 100 parts by mass, more preferably 0.05 to 50 parts by mass, even more preferably 0.1 to 10 parts by mass, and still more preferably 0.5 to 5 parts by mass; Bacopa extract is preferably 0.01 to 100 parts by mass, more preferably 0.05 to 50 parts by mass, even more preferably 0.1 to 10 parts by mass, and still more preferably 0.5 to 7 parts by mass; Moringa extract is preferably 0.01 to 100 parts by mass, more preferably 0.05 to 50 parts by mass, even more preferably 0.1 to 10 parts by mass, and still more preferably 0.5 to 5 parts by mass.

[0049] When the lutein contained in the lutein-containing composition is 1 part by mass: Flavonoids are preferably 0.001 to 5 parts by mass, more preferably 0.002 to 3 parts by mass, and even more preferably 0.005 to 1 part by mass; resveratrol is preferably 0.001 to 10 parts by mass, more preferably 0.005 to 5 parts by mass, even more preferably 0.01 to 1 part by mass, and even more preferably 0.05 to 0.5 parts by mass; curcumin is preferably 0.001 to 0.5 parts by mass.

[0050] Furthermore, when the lutein contained in the lutein-containing composition is considered as 1 part by mass: Rooibos extract is preferably 0.01 to 100 parts by mass, more preferably 0.05 to 50 parts by mass, even more preferably 0.1 to 10 parts by mass, and even more preferably 0.5 to 5 parts by mass; Rhodiola rosea extract is preferably 0.01 to 100 parts by mass, more preferably 0.05 to 50 parts by mass, even more preferably 0.1 to 10 parts by mass, and even more preferably 0.5 to 7 parts by mass; Passionflower extract is preferably 0.01 to 100 parts by mass, more preferably 0.05 to 50 parts by mass, even more preferably 0.1 to 10 parts by mass, and even more preferably 0.5 to 7 parts by mass. More preferably in parts by mass: Ginkgo biloba extract is preferably in 0.01 to 100 parts by mass, more preferably in 0.05 to 50 parts by mass, even more preferably in 0.1 to 10 parts by mass, and even more preferably in 0.5 to 7 parts by mass; Astragalus membranaceus extract is preferably in 0.01 to 100 parts by mass, more preferably in 0.05 to 50 parts by mass, even more preferably in 0.1 to 10 parts by mass, and even more preferably in 0.5 to 7 parts by mass; Albizia julibrissin extract is preferably in 0.01 to 100 parts by mass, more preferably in 0.05 to 50 parts by mass, even more preferably in 0.1 to 10 parts by mass, and even more preferably in 0.5 to 7 parts by mass.

[0051] When the lutein in the lutein-containing composition is 1 part by mass, the amount of β-caryophyllene is preferably 0.1 to 1000 parts by mass, more preferably 0.5 to 500 parts by mass, even more preferably 1 to 100 parts by mass, and still more preferably 5 to 50 parts by mass. Similarly, when the lutein in the lutein-containing composition is 1 part by mass, the amount of plasmalogen is preferably 0.001 to 1000 parts by mass, more preferably 0.005 to 500 parts by mass, even more preferably 0.01 to 100 parts by mass, and still more preferably 0.1 to 15 parts by mass.

[0052] When the amount of lutein contained in the lutein-containing composition is 1 part by mass: Vitamin B2 is preferably 0.01 to 100 parts by mass, more preferably 0.05 to 50 parts by mass, even more preferably 0.1 to 10 parts by mass, and still more preferably 0.5 to 7 parts by mass; Vitamin B6 is preferably 0.01 to 100 parts by mass, more preferably 0.05 to 50 parts by mass, even more preferably 0.1 to 10 parts by mass, and still more preferably 0.5 to 7 parts by mass; Vitamin B12 is preferably 0.000005 to 7 parts by mass, more preferably 0.00001 to 0.07 parts by mass, even more preferably 0.00005 to 0.007 parts by mass, and still more preferably 0.0001 to 0.0007 parts by mass.

[0053] Furthermore, when the lutein content in the lutein-containing composition is considered to be 1 part by mass, the respective contents of perilla oil, MCT, safflower oil, rice germ oil, flaxseed oil, and krill oil are preferably 0.5 to 500 parts by mass, more preferably 1 to 300 parts by mass, even more preferably 10 to 100 parts by mass, and even more preferably 30 to 70 parts by mass.

[0054] When the lutein contained in the lutein-containing composition is considered as 1 part by mass: α-linolenic acid is preferably 0.5 to 200 parts by mass, more preferably 1 to 100 parts by mass, even more preferably 5 to 60 parts by mass, and even more preferably 10 to 30 parts by mass; caprylic acid is preferably 0.5 to 200 parts by mass, more preferably 1 to 100 parts by mass, even more preferably 5 to 60 parts by mass, and even more preferably 10 to 20 parts by mass; capric acid is preferably 0.5 to 200 parts by mass, more preferably 1 to 100 parts by mass, even more preferably 5 to 60 parts by mass, and even more preferably 10 to 20 parts by mass. More preferably; linoleic acid is preferably 0.5 to 200 parts by mass, more preferably 1 to 100 parts by mass, more preferably 5 to 60 parts by mass, and more preferably 10 to 40 parts by mass; docosahexaenoic acid is preferably 0.1 to 200 parts by mass, more preferably 0.5 to 100 parts by mass, more preferably 1 to 20 parts by mass, and more preferably 5 to 10 parts by mass; eicosapentaenoic acid is preferably 0.05 to 100 parts by mass, more preferably 0.1 to 50 parts by mass, more preferably 0.5 to 10 parts by mass, and more preferably 1 to 5 parts by mass.

[0055] [1-3. Other ingredients] The lutein-containing composition of the present invention may contain any components in addition to lutein and certain other active ingredients. Examples of any components may include active ingredients other than lutein and certain other active ingredients (further active ingredients), as well as any other components and various additives for formulation.

[0056] Further examples of active ingredients include amino acids (such as GABA, theanine, arginine, phenylalanine, serine, threonine, tryptophan, and tyrosine), polyphenols (such as gallic acid and chlorogenic acid), lactic acid bacteria, bifidobacteria, natto bacteria, yeast, vitamins and minerals (such as vitamin B1, vitamin D3, biotin, vitamin K, calcium, manganese, zinc, iron, molybdenum, and chromium), animal materials (such as collagen and placenta), plant materials (bilberry, blackcurrant, kudzu, rice, and coconut), and dietary fiber.

[0057] Various additives are predetermined components for formulating lutein-containing compositions. For example, if the lutein-containing composition is to be made into capsules, tablets, powders, or granules, it may contain excipients, binders, disintegrants, lubricants, etc. If it is to be made into a liquid, it may generally contain water and stabilizers, etc.

[0058] [2. Uses of lutein-containing compositions] The lutein-containing composition of the present invention preferably has antioxidant activity and can be used as a retinal protective composition based on this antioxidant activity. Antioxidant activity includes suppressing oxidative stress, for example, suppressing oxidative stress caused by reactive oxygen species. Reactive oxygen species are superoxide ions (O2). ·- ), hydroxyl radical (OH · This refers to hydrogen peroxide (H2O2), singlet oxygen, etc.

[0059] It is known that when living organisms such as humans are exposed to light stimuli such as blue light and ultraviolet light, reactive oxygen species are generated in cells. For example, when the human eye is exposed to light stimuli, reactive oxygen species are generated in human retinal pigment epithelial cells, which causes oxidative stress. The lutein-containing composition of the present invention can exert antioxidant activity in cells and suppress oxidative stress. Whether or not oxidative stress is suppressed can be determined using cellular oxidative stress markers as indicators; for example, suppression of oxidative stress can be confirmed by a decrease in the expression level of TGFβ1, which has been proposed as an oxidative stress marker for human retinal pigment epithelial cells.

[0060] Lutein-containing compositions can preferably be used for retinal protection; more specifically, retinal protection includes protecting the eyes from light stimuli such as blue light and ultraviolet rays, improving blurriness and haziness (contrast sensitivity), and compensating for age-related decline in eye function. Furthermore, these protective functions can be highlighted in the product descriptions of lutein-containing compositions.

[0061] Furthermore, lutein has been reported to have a cognitive function-improving effect (see Patent Document 2 mentioned above), and it is said that at least a part of this effect is due to the antioxidant action of lutein. The lutein-containing composition of the present invention has a high antioxidant effect and can therefore be used for improving cognitive function. The lutein-containing composition of the present invention can be promoted for these cognitive improvement effects in its product introduction.

[0062] [3. Morphological properties of lutein-containing compositions] The lutein-containing composition of the present invention is used by ingestion or administration to animals (preferably mammals, more preferably humans); however, the route of administration is not particularly limited and may be oral, by injection, transdermal, ophthalmic, nasal, or vaginal, but oral administration is preferred. The lutein-containing composition can be made into a form appropriate for its method of administration.

[0063] Examples of forms of lutein-containing compositions suitable for ingestion or oral administration include tablets, capsules, powders, granules, liquids, granular preparations, gummies, sticks, plates, blocks, solids, rounds, pastes, creams, caplets, gels, chewables, and sticks. Among these, tablets, capsules, powders, granules, liquids, and gummies are preferred. Lutein-containing compositions can also be provided as supplements, as beverages in containers such as PET bottles, cans, or glass bottles, as instant powdered beverages to be dissolved in water (hot water), milk, fruit juice, or green juice, or as instant granular beverages. These are preferred because they are easy to consume with meals and enhance palatability.

[0064] Lutein-containing compositions can also be incorporated into any food as a food ingredient. Examples of foods are not particularly limited, but include beverages, frozen desserts, noodles, confectionery, processed seafood and livestock products, dairy products, oils and fats and their processed products, seasonings, retort pouch foods, etc. Examples of beverages include carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, smoothies, green juice, etc.; examples of frozen desserts include ice cream, ice sherbet, shaved ice, etc.; examples of noodles include soba, udon, vermicelli, Chinese noodles, instant noodles, etc.; examples of confectionery include candy, gum, chocolate, tablets, snacks, biscuits, jelly, jam, cream, baked goods, bread, etc.; examples of processed seafood and livestock products include kamaboko, ham, sausage, etc.; and examples of dairy products include processed milk Examples of oils and fats include fermented milk, yogurt, etc.; examples of oils and fats and their processed foods include salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, dressing, etc.; examples of seasonings include sauces, soy sauce, etc.; examples of retort pouch foods include curry, stew, oyakodon, porridge, rice gruel, chukadon, katsudon, tempuradon, gyudon, hayashi rice, omurice, oden, mapo tofu, gyoza, shumai, hamburgers, meatballs, various sauces, various soups, etc.

[0065] The lutein-containing composition may be provided, for example, as an eye drop. The lutein-containing composition as an eye drop is preferably an aqueous solution, suspension, or oily liquid. The lutein-containing composition may also be provided as a topical preparation (such as a transdermal preparation). The lutein-containing composition as a topical preparation is preferably an ointment, cream, aqueous or oily liquid.

[0066] [4. How to improve antioxidant capacity] This invention provides a method for improving the inherent antioxidant capacity of lutein. As shown in the aforementioned Patent Documents 1 to 3, lutein is known to have antioxidant properties. This invention can enhance the antioxidant effect of lutein by combining it with certain other active ingredients. For example, by administering the lutein-containing composition of this invention to an animal (which may be an animal other than a human), it can be delivered to cells and improve the antioxidant capacity of lutein in those cells. Antioxidant capacity may include, but is not particularly limited to, suppressing oxidative stress caused by reactive oxygen species.

[0067] [5. How to protect your retina] This invention provides a method for protecting the retina from reactive oxygen species. As shown in Patent Document 1, lutein is present in the macula and lens of the retina and is said to inactivate reactive oxygen species in the eye. Therefore, by administering the lutein-containing composition of this invention to an animal (which may be an animal other than a human), it can be delivered to the retina and more effectively inactivate reactive oxygen species in the eye. [Examples]

[0068] The present invention will be described in more detail below with reference to examples. The scope of the present invention should not be construed as being limited by reference to the description of these examples.

[0069] [A. Relationship between TGFβ1 gene expression in human retinal pigment epithelial cells and hydrogen peroxide concentration] Frozen stocks of human retinal pigment epithelial cells (HRPECs) were thawed in a 37°C water bath, and the entire volume was seeded into T25 flasks. The T25 flasks were pre-treated with Poly-L-Lysin (2 μg / cm³) for at least one hour before seeding. 2 Cells coated with ) were used. The culture medium was changed as needed, and frozen stocks of cells were prepared and subcultured.

[0070] HRPEC cells whose proliferation had been confirmed were seeded at a rate of 3,125 cells per well in a 384-plate. 92 hours after seeding, hydrogen peroxide was added to achieve four different final concentrations (0 μM, 100 μM, 500 μM, and 1000 μM). TGFβ1 expression was analyzed using the TaqMan Gene Expression Cells-to-CT Kit, where cDNA was synthesized by cell lysis and reverse transcription. For real-time PCR, 10 μL of reaction solution was prepared per reaction using 5 μL of TaqMan® Gene Expression Master Mix (2X), 2 μL of cDNA solution, 0.5 μL of TaqMan probe (TGFβ1, RPLP0), and 2 μL of nuclease-freewater. The reaction was carried out at 50°C for 2 minutes, followed by heating at 95°C for 10 minutes, then at 95°C for 15 seconds, and finally at 60°C for 60 seconds, repeated 40 times. The obtained Ct values ​​were corrected using an internal standard (RPLP0), and the relative expression levels were calculated. These results are shown in Figure 1.

[0071] As shown in Figure 1, when the expression level of TGFβ1 at a hydrogen peroxide concentration of 0 (- hydrogen peroxide concentration) is set to 1, the expression level of TGFβ1 at a hydrogen peroxide concentration of 100 μM was 1.04, at 500 μM it was 1.38, and at 1000 μM it was 1.77. Thus, it was confirmed that stimulating human retinal pigment epithelial cells with reactive oxygen species increases the expression level of TGFβ1. Therefore, in the following test, using the expression level of TGFβ1 as an oxidative stress marker, we confirmed how the expression level of TGFβ1 in human retinal pigment epithelial cells at a hydrogen peroxide concentration of 500 μM changes with the lutein-containing composition of the present invention.

[0072] [Effects of each test substance on the expression level of B.TGFβ1 (relationship with concentration)] Human retinal pigment epithelial cells (ScienCell #6540) were placed in a 96-well plate at a rate of 1 × 10⁶ cells per well. 4 Cells were seeded. After 72 hours, lutein, oil sample, and powder sample were added at the specified concentrations. The concentrations of lutein and powder sample were set to 0.01, 0.03, 0.1, 0.3, 1.3, and 10 μg / ml, and the concentrations of oil sample were set to 0.00001, 0.00003, 0.0001, 0.0003, 0.001, 0.003, and 0.01 by mass%. Oil samples: Perilla oil, MCT oil, safflower oil, rice germ oil, flaxseed oil, plasmalogen, β-caryophyllene, krill oil, olive oil Powdered samples: Vitamin B2, Vitamin B6, Vitamin B12, Rooibos extract, Pomegranate extract, Rhodiola rosea extract, Passionflower extract, Ginkgo biloba extract, Albizia julibrissin extract, Bacopa extract, Moringa extract, Resveratrol, Astragalus membranaceus extract

[0073] After 20 hours, hydrogen peroxide prepared in serum-free medium was added at a final concentration of 500 μM. After another 20 hours, a template for quantitative PCR was prepared using Cells-to-CtKit (Thermo Fisher Scientific). Subsequently, quantitative PCR was performed, and the expression level of TGFβ1 at each test substance addition was calculated, with the relative expression level of TGFβ1 in the unadded and unadded samples set to 1. As a result, both the lutein and powder samples showed a decrease in expression at one of the following concentrations: 0.01, 0.03, 0.1, 0.3, 1.3, and 10 μg / ml; both the oil samples showed a decrease in expression at one of the following concentrations: 0.00001, 0.00003, 0.0001, 0.0003, 0.001, 0.003, and 0.01 mass%. Furthermore, no cytotoxicity was observed at any of the concentrations. Therefore, in the tests described later in [Effects of each test substance on the expression level of C.TGFβ1], the addition concentrations of the powder sample and oil sample were set to 10 μg / ml and 0.01% by mass, respectively, which are the maximum addition concentrations within the test range.

[0074] The lutein and the other 22 active ingredients (A-U and V) are as shown in the table below. "Lutemax® 2020," used as the lutein, contains 20% by mass of lutein derived from marigolds. [Table 1]

[0075] [Effects of each test substance on the expression level of C.TGFβ1] Human retinal pigment epithelial cells (HRPECs) were seeded at a rate of 3,125 cells per well in a 384-plate. 72 hours after seeding, the following conditions were observed: "no active ingredient added," "lutein (Lutemax® 2020) added alone (10 μg / ml)," "other active ingredients added alone (22 types)," and "a combination of lutein (10 μg / ml) and other active ingredients (22 types) added." The concentration of other active ingredients was 0.01% by mass for oil samples and 10 μg / ml for powder samples.

[0076] After 20 hours, hydrogen peroxide was added to a concentration of 500 μM. After another 20 hours, cell lysis and reverse transcription were performed using the TaqMan Gene Expression Cells-to-CT Kit to synthesize reverse transcripts, and TGFβ1 expression was quantified by real-time PCR. The obtained values ​​were statistically tested for significance using the Steel test and t-test. These results are shown in Figures 2A to 2U.

[0077] As shown in Figure 20, compared to the control group without any active ingredient, the expression level of TGFβ1 decreased slightly with the addition of lutein alone, and did not decrease (in fact increased) with the addition of perilla oil alone. In contrast, when the same concentrations of lutein and perilla oil were added in combination, the expression level of TGFβ1 decreased significantly.

[0078] Thus, although they do not reduce TGFβ1 expression levels on their own, moringa extract (Figure 2C), rafuma extract (Figure 2E), passionflower extract (Figure 2F), safflower oil (Figure 2Q), rice germ oil (Figure 2R), and flaxseed oil (Figure 2S) were found to be effective ingredients that reduce TGFβ1 expression levels when combined with lutein.

[0079] Furthermore, pomegranate extract (Figure 2A), bacopa extract (Figure 2B), rooibos extract (Figure 2D), ginkgo extract (Figure 2G), astragalus extract (Figure 2H), silk tree extract (Figure 2I), resveratrol (Figure 2J), β-caryophyllene (Figure 2K), vitamin B2 (Figure 2L), vitamin B6 (Figure 2M), vitamin B12 (Figure 2N), MCT (Figure 2P), plasmalogen (Figure 2T), and krill oil (Figure 2U) were found to be active ingredients that, while reducing TGFβ1 expression levels on their own (whether statistically significant or not), further reduce TGFβ1 expression levels (enhancing the reduction effect) when combined with lutein.

[0080] On the other hand, as shown in Figure 2V, olive oil alone reduced TGFβ1 expression, but when combined with lutein, it increased TGFβ1 expression (compared to when olive oil was used alone). Thus, it can be seen that even if a component reduces TGFβ1 expression on its own, an additive or synergistic effect with lutein is not necessarily obtained.

[0081] As described above, the lutein-containing composition of the present invention exhibits high antioxidant activity. This antioxidant activity can be confirmed using the expression level of TGFβ1 in human retinal pigment epithelial cells as an indicator. Therefore, the lutein-containing composition can be effectively used to suppress oxidative stress in the eye. [Industrial applicability]

[0082] The lutein-containing composition of the present invention has high antioxidant activity and can therefore be applied to the same uses as conventional lutein-containing compositions. In particular, the lutein-containing composition of the present invention can be used by humans through ingestion or oral administration to protect against eye problems, especially eye damage caused by reactive oxygen species. Thus, the lutein-containing composition of the present invention can contribute to human health.

Claims

1. A composition containing lutein and one or more selected from the group consisting of (a) to (e) below: (a) At least one plant material selected from pomegranate, bacopa, and moringa; (b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; (c) β-caryophyllene or plasmalogen; (d) At least one vitamin selected from vitamin B2, vitamin B6, and vitamin B12; (e) At least one fatty acid selected from alpha-linolenic acid, caprylic acid, capric acid, linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid.

2. A composition containing lutein and one or more selected from the group consisting of (a) to (e') below: (a) At least one plant material selected from pomegranate, bacopa, and moringa; (b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; (c) β-caryophyllene or plasmalogen; (d) At least one vitamin selected from vitamin B2, vitamin B6, and vitamin B12; (e') At least one oil or fat selected from perilla oil, MCT oil, safflower oil, rice germ oil, flaxseed oil, and krill oil.

3. The composition according to claim 1 or 2, which is for antioxidant purposes.

4. The antioxidant composition according to claim 3, for protection from reactive oxygen species.

5. The composition according to claim 1 or 2, which is for retinal protection.

6. The retinal protective composition according to claim 5, which is for protecting the retina from reactive oxygen species.

7. The composition according to claim 1 or 2, for oral use.

8. A capsule, tablet, powder, granule, or liquid preparation comprising the composition according to claim 1 or 2.

9. A method for protecting the retina from reactive oxygen species, characterized by using a composition containing lutein and one or more selected from the group consisting of (a) to (e) below: (a) At least one plant material selected from pomegranate, bacopa, and moringa; (b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; (c) β-caryophyllene or plasmalogen; (d) At least one vitamin selected from vitamin B2, vitamin B6, and vitamin B12; (e) At least one fatty acid selected from alpha-linolenic acid, caprylic acid, capric acid, linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid.

10. A method for protecting the retina from reactive oxygen species, characterized by using a composition containing lutein and one or more selected from the group consisting of (a) to (e') below: (a) At least one plant material selected from pomegranate, bacopa, and moringa; (b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; (c) β-caryophyllene or plasmalogen; (d) At least one vitamin selected from vitamin B2, vitamin B6, and vitamin B12; (e') At least one oil or fat selected from perilla oil, MCT oil, safflower oil, rice germ oil, flaxseed oil, and krill oil.

11. A method for improving the antioxidant capacity of lutein, characterized by using one or more selected from the group consisting of (a) to (e) below: (a) At least one plant material selected from pomegranate, bacopa, and moringa; (b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; (c) β-caryophyllene or plasmalogen; (d) At least one vitamin selected from vitamin B2, vitamin B6, and vitamin B12; (e) At least one fatty acid selected from alpha-linolenic acid, caprylic acid, capric acid, linoleic acid, docosahexaenoic acid, and eicosapentaenoic acid.

12. A method for improving the antioxidant capacity of lutein, characterized by using one or more selected from the group consisting of (a) to (e') below: (a) At least one plant material selected from pomegranate, bacopa, and moringa; (b) At least one polyphenol selected from flavonoids, curcumin, and resveratrol; (c) β-caryophyllene or plasmalogen; (d) At least one vitamin selected from vitamin B2, vitamin B6, and vitamin B12; (e') At least one oil or fat selected from perilla oil, MCT oil, safflower oil, rice germ oil, flaxseed oil, and krill oil.

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