Omentum protection composition

Abstract

To provide a retinal protective composition capable of more effectively protecting retinal pigment epithelial cells from damage caused by active oxygen and suppressing retinal disorders. SOLUTION: The retinal protective composition is characterized by containing lutein and a specific component such as at least one plant material selected from kudzu, rice, and coconut as active ingredients.

Description

Technical Field

[0001] The present invention relates to a retinal protective composition, and more particularly to a retinal protective composition containing lutein and specific other components as active ingredients.

Background Art

[0002] It is known that the function of the retinal pigment epithelium, which is involved in the repair and regeneration of photoreceptor cells, declines with aging. When a person is young, the body has sufficient SOD enzymes that decompose reactive oxygen species generated inside cells, preventing the adverse effects of reactive oxygen species. However, as people age, the function of SOD enzymes declines, and the function of the retinal pigment epithelium also declines.

[0003] On the other hand, lutein is present in the macula lutea of the retina and the lens together with zeaxanthin, and is said to have an SOD-like action and remove reactive oxygen species generated in the eye, and is known to be effective in maintaining eye function and preventing and treating cataracts, age-related macular degeneration, etc. (see, for example, Patent Documents 1 and 2).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0005] An object of the present invention is to provide a retinal protective composition capable of effectively protecting retinal pigment epithelial cells from damage by reactive oxygen species and suppressing retinal disorders.

Means for Solving the Problems

[0006] The inventors of this invention have diligently investigated and researched the protection of retinal pigment epithelial cells, which play a crucial role in the retina, from reactive oxygen species. As a result, they discovered that a high protective effect on retinal pigment epithelial cells can be obtained by combining lutein with certain other components, leading to the completion of this invention. Specifically, they found that by combining lutein with certain other components that have little to no protective ability against retinal pigment epithelial cells, damage to retinal pigment epithelial cells caused by reactive oxygen species can be more effectively suppressed.

[0007] In other words, the present invention relates to a retinal protective composition characterized by containing lutein and at least one component selected from the group consisting of (a) to (d) below as active ingredients. (a) At least one plant material selected from kudzu, rice, and coconut palm. (b) At least one amino acid selected from arginine, phenylalanine, serine, threonine, tryptophan, and tyrosine. (c) At least one polyphenol selected from gallic acid and chlorogenic acid (d) At least one vitamin or mineral selected from vitamin B1, vitamin D3, biotin, vitamin K, calcium, manganese, zinc, iron, molybdenum, and chromium.

[0008] The retinal protective composition of the present invention can be used as an eye function maintenance agent having a retinal protective effect.

[0009] The retinal protective composition of the present invention may be obtained by adding an active ingredient consisting of lutein and at least one component selected from the group consisting of (a) to (d).

[0010] Furthermore, the retinal protective composition of the present invention is preferably for oral use, and is preferably in the form of tablets, capsules, powders, granules, or liquids.

[0011] Furthermore, the present invention relates to a method for maintaining eye function (excluding medical procedures) characterized by administering the retinal protective composition of the present invention described above. [Effects of the Invention]

[0012] The retinal protective composition of the present invention can effectively protect retinal pigment epithelial cells from damage caused by reactive oxygen species and suppress retinal damage. [Brief explanation of the drawing]

[0013] [Figure 1] This figure shows the expression level of TGFβ1, an oxidative stress marker, when the retinal protective composition (lutein + plant material) of the present invention is applied to human retinal pigment epithelial cells (ARPE-19). The upper left figure shows the composition using kudzu as the plant material, the upper right figure shows the composition using rice (rice bran) as the plant material, and the lower left figure shows the composition using coconut palm as the plant material. [Figure 2] This figure shows the expression level of TGFβ1, an oxidative stress marker, when the retinal protective composition (lutein + amino acid) of the present invention is applied to human retinal pigment epithelial cells (ARPE-19). The upper left figure shows the expression level when arginine is used as the amino acid, the upper right figure shows the expression level when phenylalanine is used as the amino acid, the lower left figure shows the expression level when serine is used as the amino acid, and the lower right figure shows the expression level when threonine is used as the amino acid. [Figure 3] This figure shows the expression level of TGFβ1, an oxidative stress marker, when the retinal protective composition of the present invention (lutein + amino acid) is applied to human retinal pigment epithelial cells (ARPE-19). The left figure shows the expression level when tryptophan is used as the amino acid, and the right figure shows the expression level when tyrosine is used as the amino acid. [Figure 4] This figure shows the expression level of TGFβ1, an oxidative stress marker, when the retinal protective composition (lutein + polyphenol) of the present invention is applied to human retinal pigment epithelial cells (ARPE-19). The left figure shows the result when gallic acid is used as the polyphenol, and the right figure shows the result when chlorogenic acid is used as the polyphenol. [Figure 5]It is a diagram showing the expression level of TGFβ1, which is an oxidative stress marker, when the retinal protection composition (lutein + vitamins) of the present invention is applied to human retinal pigment epithelial cells (ARPE-19). The upper left figure shows the case where vitamin B1 is used as vitamins, the upper right figure shows the case where vitamin D3 is used as vitamins, the lower left figure shows the case where biotin is used as vitamins, and the lower right figure shows the case where vitamin K is used as vitamins. [Figure 6] It is a diagram showing the expression level of TGFβ1, which is an oxidative stress marker, when the retinal protection composition (lutein + minerals) of the present invention is applied to human retinal pigment epithelial cells (ARPE-19). The upper left figure shows the case where calcium is used as minerals, the upper right figure shows the case where manganese is used as minerals, the lower left figure shows the case where zinc is used as minerals, and the lower right figure shows the case where iron is used as minerals. [Figure 7] It is a diagram showing the expression level of TGFβ1, which is an oxidative stress marker, when the retinal protection composition (lutein + minerals) of the present invention is applied to human retinal pigment epithelial cells (ARPE-19). The left figure shows the case where molybdenum is used as minerals, and the right figure shows the case where chromium is used as minerals.

Mode for Carrying Out the Invention

[0014] The retinal protection composition of the present invention is characterized by containing lutein and at least one component selected from the group consisting of the following (a) to (d) (hereinafter sometimes referred to as other components) as active ingredients. The components of the following (a) to (d) used together with lutein may be used alone (for example, component (a)) or in combination of two or more. When two or more other components are used in combination, it is preferable to combine other components having a high synergistic effect with lutein.

[0015] The retinal protection composition of the present invention can more effectively protect retinal pigment epithelial cells from damage by reactive oxygen species, suppress retinal disorders, delay eye aging, and maintain eye function. In addition, it can suppress the occurrence of retinal diseases such as age-related macular degeneration, retinitis pigmentosa, central serous chorioretinopathy, macular retinal epitheliopathy, and macular hole. Therefore, the retinal protection composition of the present invention can be used as an eye function maintenance agent, a retinal protection agent, a retinal disorder inhibitor, a retinal disease preventive agent, and the like.

[0016] [Lutein] The lutein used in the present invention is a kind of carotenoid present in the leaves, flowers, fruits, etc. of plants, and those derived from plants can be used. For example, those derived from marigold containing a large amount of lutein can be used. In addition, those produced by synthesis can also be used.

[0017] [Other components] (a) Plant materials In the retinal protection composition of the present invention, it is preferable to use at least one plant material selected from kudzu, rice, and coconut as an active ingredient together with lutein.

[0018] These plant materials can be any part of the plant, such as leaves, stems, roots, flowers, fruits, trunks, branches, etc. In addition to the plant materials themselves (including dried products), processed products of plant materials such as their pulverized products, squeezed juices, and extracts can be used. Examples of the pulverized products include powders and granules. The squeezed juice or extract may be in a liquid state, but can also be used as a paste or a dry powder. The extract can be obtained by extraction using an appropriate solvent, and examples of the solvent include water (hot water), ethanol, and aqueous ethanol. These plant materials can be commercially available ones.

[0019] Kudzu is a climbing perennial plant belonging to the genus Pueraria in the family Fabaceae. The parts of the plant used as material in this invention are preferably the flowers and roots, with the flowers being particularly preferred. Kudzu flowers may be collected at any stage from bud to fully bloomed flower, or a mixture of flowers collected at each stage may be used. There are no particular restrictions on the type of kudzu, but examples include Pueraria thomsonii, Pueraria lobata, and Pueraria thunbergiana.

[0020] Rice is a plant belonging to the genus Rumex in the family Poaceae. The parts of the plant used as material in this invention are preferably the outer husk and embryo of brown rice, and more specifically, rice bran obtained as a by-product during the milling of brown rice is preferred. There are no particular restrictions on the type of rice, but examples include Japonica and Indica varieties.

[0021] The coconut palm is a plant belonging to the palm family, and the part used as the plant material in this invention is preferably the fruit (endosperm).

[0022] (b) amino acids In the retinal protective composition of the present invention, it is preferable to use, along with lutein, at least one amino acid (including a salt) selected from arginine, phenylalanine, serine, threonine, tryptophan, and tyrosine as an active ingredient. Examples of salts include sodium salts and hydrochloride salts.

[0023] (c) Polyphenols In the retinal protective composition of the present invention, it is preferable to use at least one polyphenol selected from gallic acid and chlorogenic acid as an active ingredient, along with lutein.

[0024] (d) Vitamins and minerals In the retinal protective composition of the present invention, it is preferable to use, along with lutein, at least one vitamin or mineral selected from vitamin B1, vitamin D3, biotin, vitamin K, calcium, manganese, zinc, iron, molybdenum, and chromium as an active ingredient. Note that the minerals of the present invention, calcium, manganese, zinc, iron, molybdenum, and chromium, include compounds containing these metals.

[0025] The retinal protective composition of the present invention can be used as an eye function maintenance agent having a retinal protective effect. Such an eye function maintenance agent is not particularly limited as long as it contains lutein and other specified components and can be distinguished from other products as a product in that it is used to maintain eye function. For example, the scope of the present invention includes products in which any of the product body, packaging, instruction manual, or promotional materials of the present invention display a statement that it has the function of maintaining eye function, such as a retinal protective effect, a retinal damage suppression effect, or a retinal disease prevention effect. Examples include so-called health foods such as pharmaceuticals (including quasi-drugs), cosmetics, and functional foods whose efficacy has been approved by a designated institution, such as Foods for Specified Health Uses, Foods with Nutritional Function Claims, and Foods with Function Claims. Examples of so-called health foods include those that display statements such as "maintain the amount of pigment in the macula of the eye," "for age-related eye problems," "protect the eyes from light stimulation," "for blue light countermeasures," "for LCD light countermeasures," "when you are tired from reading, using a computer or smartphone," "for those who are concerned about blurriness," "for improving contrast sensitivity," "for tired eyes," "to improve the condition of the eyes," and "to relieve eye fatigue." The retinal protective composition of the present invention can be taken by anyone interested in the above effects, regardless of gender or age. However, it is preferable for healthy individuals (excluding those with illnesses) to take it in order to more effectively enjoy the effects of the retinal protective composition of the present invention. Furthermore, it is preferable for those who perform tasks that strain their eyes for long periods of time to take it, and especially for desk workers who work for long periods of time on computers, etc.

[0026] Furthermore, examples of the retinal protective composition of the present invention include tablets, capsules, powders, granules, liquids, granular formulations, rod-shaped formulations, plate-shaped formulations, block-shaped formulations, solid formulations, round formulations, paste-like formulations, cream-like formulations, caplet-like formulations, gel-like formulations, chewable formulations, stick-shaped formulations, and the like. Among these, the forms of tablets, capsules, powders, granules, and liquid formulations are particularly preferred. Specifically, examples include supplements, beverages in containers such as PET bottles, cans, and glass bottles, and instant powdered beverages and instant granular beverages that are dissolved in water (hot water), milk, fruit juice, green juice, etc. These are preferred because they are easy to drink with meals and can enhance palatability.

[0027] The content of lutein and other components (active ingredients) in the retinal protective composition of the present invention may be appropriately included within a range that achieves their effects.

[0028] Generally, when the retinal protective composition of the present invention is a pharmaceutical or supplement (tablet, capsule), it is preferable that the active ingredient is present in an amount of 0.01 to 100% by mass of the total on a dry weight basis, more preferably 0.1 to 85% by mass, and even more preferably 0.5 to 70% by mass.

[0029] When the retinal protective composition of the present invention is a packaged beverage (liquid), it is preferable that the active ingredient is present in an amount of 0.01 to 15% by mass of the total on a dry weight basis, more preferably 0.03 to 12.5% ​​by mass, and even more preferably 0.05 to 10% by mass.

[0030] Furthermore, when the retinal protective composition of the present invention is an instant powder beverage (powder) or an instant granular beverage (granule), it is preferable that the active ingredient is present in an amount of 0.1 to 80% by mass of the total on a dry weight basis, more preferably 0.5 to 70% by mass, and even more preferably 1 to 60% by mass.

[0031] In order to more effectively exert the effects of the present invention, it is preferable that the active ingredient constitutes 80% by mass or more of the total retinal protective composition of the present invention (excluding water) on a dry weight basis, more preferably 90% by mass or more, even more preferably 95% by mass or more, and particularly preferably 100% by mass. Furthermore, if the retinal protective composition of the present invention contains any of components (a) to (d), it is preferable that the contained components consist only of the active ingredient of the present invention. That is, if the retinal protective composition of the present invention contains, for example, component (a) (plant material), it is preferable that it is composed so as not to contain plant materials other than kudzu, rice, and coconut palm.

[0032] There are no particular restrictions on the amount of the retinal protective composition of the present invention to be ingested. However, from the viewpoint of exhibiting the effects of the present invention more significantly, it is preferable to ingest the active ingredient in an amount of 1 mg / day or more, more preferably 5 mg / day or more, and particularly preferably 10 mg / day or more. There is no particular upper limit, but for example, it is 4 g / day, and preferably 2 g / day.

[0033] The retinal protective composition of the present invention can be contained in one container, or divided into, for example, two or three containers, to constitute a one-day dose, so that the daily intake amount is the aforementioned intake amount.

[0034] The blending mass ratio of lutein and other components is preferably in the range of 0.5:1 to 70:1 on a dry weight basis, more preferably in the range of 0.75:1 to 60:1, even more preferably in the range of 1:1 to 60:1, and particularly preferably in the range of 1:1 to 50:1. By having the blending ratio of lutein and other components within the above range, the effects of the present invention can be more effectively exhibited.

[0035] The retinal protective composition of the present invention can be manufactured by known methods, with the addition of components other than the oral-acceptable active ingredient as necessary.

[0036] Furthermore, as an oral retinal protective composition of the present invention, examples include not only a retinal protective composition containing the active ingredient, but also a retinal protective composition obtained by adding the active ingredient to food (retinal protective food). For example, this could include food in which the content of the active ingredient of the present invention is increased compared to ordinary food (including natural food), or food in which the active ingredient of the present invention is added to food that does not normally contain the active ingredient of the present invention. The active ingredient may be added separately, simultaneously, or together with other ingredients other than the active ingredient.

[0037] Examples of retinal protective foods of the present invention include: beverages such as carbonated drinks, nutritional drinks, fruit drinks, lactic acid drinks, smoothies, and green juice; frozen desserts such as ice cream, ice sherbet, and shaved ice; noodles such as soba, udon, vermicelli, Chinese noodles, and instant noodles; confectionery such as candy, gum, chocolate, tablets, snacks, biscuits, jelly, jam, cream, baked goods, and bread; processed seafood and livestock products such as kamaboko, ham, and sausage; processed milk, fermented milk, Examples include dairy products such as yogurt; oils and fats such as salad oil, tempura oil, margarine, mayonnaise, shortening, whipped cream, and dressings, and their processed foods; seasonings such as sauces and soy sauce; and retort pouch foods such as curry, stew, oyakodon, porridge, rice gruel, chukadon, katsudon, tempuradon, gyudon, hayashi rice, omurice, oden, mapo tofu, gyoza, shumai, hamburgers, meatballs, various sauces, and various soups.

[0038] The present invention's method for maintaining eye function is characterized by administering the retinal protective composition of the present invention described above, but does not involve any medical procedure. The retinal protective composition of the present invention can be administered to anyone who is interested in the above effects, regardless of gender or age, but it is preferable to administer it to healthy individuals excluding those with illnesses in order to more effectively enjoy the effects of the retinal protective composition of the present invention. It is also preferable to administer it to those who perform tasks that strain their eyes for long periods of time, and it is particularly preferable to administer it to desk workers who work for long periods of time on computers, etc. As an example of the method of the invention, one can cite a method of obtaining the effect of maintaining eye function by providing the retinal protective food of the present invention in restaurants and other food service establishments. [Examples]

[0039] The present invention will be described below based on examples. [Example 1] 1.Cell culture (1) 75cm in a 37℃, 5% CO2 incubator 2 Human retinal pigment epithelial cells (ARPE-19) were cultured in flasks. The culture medium used was a 1:1 mixture of DMEM medium and F-12HAM medium, prepared to have a FBS content of 10%. (2) Cells suspended by trypsin treatment, 75 cm 2 From the flask, pour 1.0 × 10⁶ of liquid into each well of the 96-well plate. 4 Seeds were seeded at a cell density of cells / well. (3) Pre-cultured for 72 hours in a 37°C, 5% CO2 incubator. (4) After removing the culture medium from each well, 200 μL of culture medium containing the test substance, prepared to the specified concentration, was added to each well and incubated in a CO2 incubator for 20 hours.

[0040] For samples containing lutein in combination with other components, a culture medium containing the test substance at twice the concentration was prepared for each sample, and 100 μL of each was added to achieve the desired concentration. For the control sample, a 0.5% DMSO-containing medium was used for samples containing the test substance dissolved in DMSO, while a 0.25% DMSO medium was used for samples containing the other test substances.

[0041] For lutein, commercially available lutein was used. Other components used in conjunction with lutein are shown in Tables 1 to 4.

[0042] (5) After 20 hours of incubation, 50 μL of hydrogen peroxide solution prepared to 1.5 mM or 2.5 mM in serum-free medium was added and incubated for another 20 hours. For samples with other components being plant materials or vitamins, the final hydrogen peroxide concentration was 300 μM. For samples with other components being amino acids, minerals, or polyphenols, the final hydrogen peroxide concentration was 500 μM. For the control group, the final hydrogen peroxide concentration was matched to that of the test group.

[0043] 2. TGFβ1 expression analysis (1) After 20 hours of culture, remove the culture medium from the cultured cells and use CellAmp TM RNA was recovered using the Direct RNA Prep Kit for RT-PCR (Real Time) (Takara), and N=3 samples were mixed to form a single RNA sample. (2) To create a calibration curve, one sample was diluted 3-fold and 9-fold. One Step SYBR® PrimeScript TM PCR was performed using the RT-PCR Kit II (Perfect Real Time) (Takara). The primers used were TGFβ1 (QIAGEN) and RPLP0 (QIAGEN). (3) Gene expression levels in each sample were calculated using calibration curves created from samples diluted 1-fold, 3-fold, and 9-fold. The analysis was performed by relative quantification, and mRNA levels were corrected using RPLP0 (housekeeping gene) as an internal standard.

[0044] The results are shown in Tables 1 to 4 and Figures 1 to 7.

[0045] Each figure, from left to right, shows the results for "Control (hydrogen peroxide added)," "Lutein added alone," "Addition of other components alone," and "Lutein + other components added." The numbers in the explanations below the graphs indicate the sample concentration; for example, "Lutein_0.62" in the upper left graph of Figure 1 indicates lutein at 0.62 μg / mL. The concentration units for the added components are μg / mL in all graphs. The vertical axis shows "% of control."

[0046] [Table 1]

[0047] For kudzu, a hot water extract (dried powder) of the flower was used. For the rice bran, I used a commercially available product. For the coconut, we used commercially available coconut milk that had been dried and the oil removed. For mugwort, we used a finely ground powder of fresh leaves. For the maqui berry, we used commercially available dried fruit powder.

[0048] [Table 2]

[0049] [Table 3]

[0050] [Table 4]

[0051] As shown in Tables 1 to 4 and Figures 1 to 7, combining lutein with specific other components of the present invention synergistically reduced the expression level of TGFβ1 in human retinal pigment epithelial cells (ARPE-19) due to oxidative stress. Therefore, the retinal protective composition of the present invention can effectively protect retinal pigment epithelial cells.

[0052] [Example 2] (Manufacturing of tablets) We manufactured a tablet (200 mg) containing the following ingredients.

[0053] Lutein (marigold extract) 10mg Bilberry extract 60mg Blueberry extract 50mg Calcium stearate 5mg Arginine 1.5mg Phenylalanine 1.5 mg Tryptophan 1 mg Chlorogenic acid 1 mg Vitamin B1 0.5mg Vitamin K 0.5mg Calcium chloride 0.5 mg Zinc gluconate 0.5 mg Cellulose residue

[0054] Take two of the above tablets daily with water without chewing.

[0055] [Example 3] (Manufacturing of capsules) The following mixture was enclosed in soft capsules to produce capsules.

[0056] weight ratio Lutein (Marigold Extract) 30% (20mg as lutein) Safflower oil 50% Beeswax 10% Kudzu flower extract 2% Blueberry extract 1% Water-soluble β-carotene powder 0.2% Haematococcus algae pigment 0.2% Vitamin B12 0.01% Biotin 0.01% Gallic acid 0.01% Vitamin E 0.01% Iron chloride 0.01%

[0057] Take one capsule a day with water without chewing.

[0058] [Example 4] (Manufacture of granules) The following ingredients were mixed and a granular preparation (3000 mg) was manufactured by a conventional method.

[0059] Lutein (marigold extract) 15mg Pine bark extract 50mg Coconut milk 200mg Aspartame 500mg Tyrosine 50mg Threonine 50mg Tryptophan 30mg Chlorogenic acid 20 mg Vitamin B1 5mg Vitamin K 5mg Calcium chloride 2mg Copper gluconate 1 mg Dextrin remaining

[0060] Take one packet of the above granules with water daily.

[0061] [Example 6] (Production of liquid formulation) A liquid preparation (125 mL) consisting of the following ingredients was manufactured.

[0062] Lutein (marigold extract) 18mg Bilberry extract 150mg Blackcurrant extract 50mg Rice bran extract 25mg Vitamin C 10mg Citric acid 5mg Arginine 1.5mg Phenylalanine 1.5 mg Tryptophan 1 mg Vitamin B1 0.5mg Vitamin K 0.5mg Calcium chloride 0.5 mg Zinc gluconate 0.5 mg water remainder

[0063] Take one pack of the above liquid medication per day. [Industrial applicability]

[0064] The retinal protective composition of the present invention has a high retinal protective effect and can be used as an oral preparation, thus the present invention has high industrial utility.

Claims

1. An oral composition for retinal protection, comprising lutein and at least one component selected from the following components (a) and (b): (a) at least one polyphenol selected from gallic acid and chlorogenic acid (b) at least one vitamin or mineral selected from vitamin D3, biotin, vitamin K, calcium, manganese, zinc, iron, molybdenum, and chromium;

2. An oral composition for retinal protection containing lutein as an active ingredient, further comprising at least one component selected from the following components (a) and (b): (a) at least one polyphenol selected from gallic acid and chlorogenic acid (b) at least one vitamin or mineral selected from vitamin D3, biotin, vitamin K, calcium, manganese, zinc, iron, molybdenum, and chromium;

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