Elevated blood cholesterol level inhibiting composition

Abstract

To provide a composition having remarkably improved elevated blood cholesterol level inhibitory action.SOLUTION: A composition comprising chitosan and at least one material selected from the group consisting of the following (a) and (b): (a) at least one functional material selected from the group consisting of resveratrol, lycopene, soybean isoflavone, nattokinase, cacao polyphenol, octacosanol, fucoidan, and citrulline; and SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a composition having an effect of suppressing an increase in blood cholesterol, and more particularly to a composition having an effect of suppressing an increase in blood cholesterol, which contains chitosan and a specific material.

[0002] Chitosan is known to have various functions for regulating the body, one of which is the suppression of blood cholesterol levels, but this effect alone is not necessarily sufficient.

[0003] Other functions of chitosan have been reported, such as an effect of improving serum uric acid levels (see Patent Document 1) and an antioxidant effect (see Patent Document 2). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2009-120502 [Patent Document 2] Japanese Patent Application Laid-Open No. 2005-075957 Summary of the Invention [Problem to be solved by the invention]

[0005] An object of the present invention is to provide a composition having a dramatically improved effect of suppressing an increase in blood cholesterol. [Means for solving the problem]

[0006] As a result of extensive research and study into the effect of chitosan in inhibiting the elevation of blood cholesterol levels, the inventors discovered that by combining chitosan with a specific material, the effect of inhibiting the elevation of blood cholesterol levels can be synergistically improved, leading to the completion of the present invention.

[0007] That is, the present invention is as follows. [1] A composition for suppressing an increase in blood cholesterol, comprising chitosan and at least one material selected from the group consisting of the following (a) and (b): (a) at least one functional material selected from resveratrol, lycopene, soy isoflavone, nattokinase, cocoa polyphenols, octacosanol, fucoidan, and citrulline; (b) at least one plant material selected from noni leaves, chia seeds, olive fruits, and flaxseeds; [2] The composition according to [1], which is in the form of a tablet, capsule, powder, granules, or liquid. [3] The composition according to [1] or [2], characterized in that it is a food composition. [Effects of the Invention]

[0008] According to the composition of the present invention, the combination of chitosan and a specific material can synergistically improve the blood cholesterol elevation suppressing effect. [Brief explanation of the drawings]

[0009] [Figure 1] FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan+resveratrol). [Figure 2] FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan+lycopene). [Figure 3] FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan+soy isoflavone). [Figure 4] FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan + nattokinase). [Figure 5] FIG. 1 is a graph showing the blood cholesterol elevation inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan + cacao polyphenols). [Figure 6]FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan+octacosanol). [Figure 7] FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan+fucoidan). [Figure 8] FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan + citrulline). [Figure 9] FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan+noni leaf). [Figure 10] FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan + chia seeds). [Figure 11] FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan + olive fruit). [Figure 12] FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan+flaxseed). DETAILED DESCRIPTION OF THE INVENTION

[0010] The composition of the present invention is characterized by containing chitosan and at least one material selected from the group consisting of the following (a) and (b) (hereinafter, sometimes referred to as other material). The materials (a) and (b) to be used together with chitosan may be used alone or in combination of two or more. When two or more other materials are used in combination, it is preferable to combine other materials that have a high synergistic effect with chitosan.

[0011] The composition of the present invention can synergistically improve the effect of suppressing the increase in blood cholesterol (LDL cholesterol) by combining chitosan with a specific material, and therefore the composition of the present invention is also useful for preventing arteriosclerosis.

[0012] [Chitosan] The chitosan used in the composition of the present invention is a basic dietary fiber having an amino group, and examples thereof include those obtained from the shells of crabs, shrimp, insects, etc., those obtained from the cell walls of mushrooms, filamentous fungi, etc., and those obtained from the midbone (cartilage) of squid. Among these, those obtained from crabs, shrimp, etc. are preferred. The chitosan of the present invention may contain chitin remaining in the chitosan chain, or may be in the form of a salt.

[0013] Chitosan can be obtained, for example, by the following method. First, crab shells, shrimp shells, etc. are crushed and the crushed shells are treated with an acid such as hydrochloric acid to remove calcium. Next, the crushed shells are treated with an alkali such as caustic soda to remove proteins, thereby obtaining chitin. This is then further treated with an alkali such as caustic soda to obtain chitosan.

[0014] [Other materials] (a) Functional materials In the composition of the present invention, it is preferable to use at least one functional material selected from resveratrol, lycopene, soybean isoflavone, nattokinase, cacao polyphenol, octacosanol, fucoidan, and citrulline together with chitosan.

[0015] (resveratrol) The resveratrol of the present invention is not particularly limited as long as it is a type of stilbenoid (stilbene derivative) polyphenol and has the systematic name 3,5,4'-trihydroxy-trans-stilbene. Resveratrol is contained in natural products such as grapes, apple berries, cowberries, and Indian elm trees. In the composition of the present invention, processed products (dried products, crushed products, squeezed juice, extracts, purified products, etc.) of such natural products may be used, or chemically synthesized products may be used.

[0016] (lycopene) The lycopene of the present invention has the chemical formula C 40 H 56There are no particular limitations on the carotenoid as long as it is expressed as a lycopene having a molecular weight of 536.87. Lycopene belongs to the carotenes, a type of carotenoid, and is a red pigment that exhibits an absorption maximum at 474 nm (acetone), and is known for its extremely high antioxidant and whitening effects. Lycopene exists as cis and trans isomers of the conjugated double bond at the center of the molecule, and examples of such isomers include all-trans isomer, 9-cis isomer, and 13-cis isomer. In the present invention, the lycopene may be any of the above-mentioned isomers.

[0017] Lycopene is naturally contained in natural products such as tomatoes, persimmons, watermelons, pink grapefruits, etc. In the composition of the present invention, processed products (dried products, crushed products, squeezed juice, extracts, purified products, etc.) of such natural products may be used, or chemically synthesized products may be used.

[0018] (soy isoflavones) Soybean isoflavones are a type of flavonoid found mainly in soybean germ. The soybean isoflavones of the present invention may be aglycones or glycosides. Furthermore, in the composition of the present invention, the soybean isoflavones may be purified, or processed soybeans (dried, pulverized, squeezed, extract, etc.) may also be used.

[0019] (Nattokinase) Nattokinase is an enzyme purified from Bacillus subtilis var. natto, which is contained in natto. In the composition of the present invention, purified nattokinase may be used, but processed natto (dried product, pulverized product, squeezed juice, extract, etc.) may also be used.

[0020] (cocoa polyphenols) Cocoa polyphenols are polyphenols contained in cocoa beans, the raw material for chocolate and cocoa, and are a mixture of compounds (flavanols) mainly consisting of epicatechin and catechin. In the composition of the present invention, the cocoa polyphenols may be purified, or processed cocoa beans (dried, ground, squeezed, extracted, etc.) may also be used.

[0021] (Octacosanol) Octacosanol, also known as octacosyl alcohol, is an alcohol found in plant leaves and the skins of fruits such as apples and grapes. In the composition of the present invention, processed products (dried products, crushed products, squeezed juice, extracts, purified products, etc.) of such natural products may be used, or chemically synthesized products may be used.

[0022] (Fucoidan) Fucoidan is a polysaccharide whose main sugar is fucose, to which sulfuric acid and uronic acid are bound, and is known to have anti-cancer, anti-ulcer, and cholesterol-lowering effects. Fucoidan is contained in seaweed, kelp, wakame seaweed, mozuku seaweed, and hijiki seaweed, and is particularly high in kagome kelp and mozuku seaweed, and is preferably used in the present invention. In the composition of the present invention, processed products of such natural products (dried products, pulverized products, squeezed juice, extracts, purified products, etc.) or chemically synthesized products may be used.

[0023] (Citrulline) The citrulline of the present invention may be L-citrulline or D-citrulline, but preferably L-citrulline.Citrulline can be obtained by chemical synthesis, fermentation, or any other method of production.In addition, citrulline can be in the form of a salt, and the salt is not particularly limited as long as it is a pharmaceutically acceptable salt, and examples thereof include inorganic acid salts, organic acid salts, metal salts, and ammonium salts.

[0024] (b) Plant material In the composition of the present invention, it is preferable to use at least one plant material selected from noni leaves, chia seeds, olive fruits, and flaxseeds together with chitosan.

[0025] These plant materials are preferably used as processed plant products such as dried plants, crushed plants, juices, and extracts. Crushed plants include powders and granules. Juices and extracts may be in liquid form, but can also be used as pastes or dry powders. Extracts can be obtained by extraction using an appropriate solvent, and examples of the solvent that can be used include water (warm water, hot water), ethanol, and aqueous ethanol. Commercially available plant materials may be used.

[0026] (Noni leaves) Noni is an evergreen tree of the genus Morinda in the family Rubiaceae, also known as Yaeyama Aoki (Yaeyama Aoki). Its scientific name is Morinda citrifolia. In the present invention, it is preferable to use crushed Noni leaves.

[0027] (chia seeds) Chia is an annual plant of the Lamiaceae family, and its scientific name is Salvia hispanica. Chia seeds are rich in omega-3 fatty acids. In the present invention, it is preferable to use an ethanol or hydroethanol extract of chia seeds.

[0028] (Olive fruit) Olives are evergreen trees of the Oleaceae family, and their scientific name is Olea europaea. Olive fruits contain healthy components such as oleic acid and vitamin E, and are used to produce olive oil and pickles. In the present invention, it is preferable to use fruit juice squeezed from olive fruits, which can be appropriately concentrated before use.

[0029] (linseed) Flax is an annual plant of the Linaceae family, and its scientific name is Linum usitatissimum. Flaxseed is the seed of the flax plant, and is rich in α-linolenic acid, lignans, and dietary fiber, and has strong antioxidant properties. In the present invention, it is preferable to use ground flaxseed.

[0030] The composition of the present invention has the effect of suppressing an increase in blood cholesterol, and can be used, for example, as a pharmaceutical product (including quasi-drugs), a so-called health food such as a functional food whose efficacy has been approved by a designated organization, such as a food for specified health uses, a food with nutrient function claims, or a food with functional claims, or as a general food, a food additive, or a feed.

[0031] The composition of the present invention can be used as a blood cholesterol-lowering composition for suppressing blood cholesterol elevation. Such a blood cholesterol-lowering food product is not particularly limited as long as it contains chitosan and a specified material and can be distinguished from other products in that it is used to suppress blood cholesterol elevation. For example, the scope of the present invention includes a product that displays on the product itself, packaging, instructions, or promotional materials that it has the function of suppressing blood cholesterol elevation. Note that the blood cholesterol-lowering composition of the present invention is not limited to a product that displays the combined components of the present invention (chitosan and other specified materials) as the active ingredient for suppressing blood cholesterol elevation on the product packaging, etc. For example, the active ingredient may not be specified, and the product may display only chitosan as the active ingredient.

[0032] Specifically, examples of the composition of the present invention for suppressing an increase in blood cholesterol include pharmaceuticals (including quasi-drugs) and so-called health foods. Examples of so-called health foods include those labeled as "suppresses an increase in cholesterol," "for those concerned about cholesterol," "suppresses cholesterol absorption," and "for those with high cholesterol."

[0033] Examples of the form of the composition of the present invention include tablets, capsules, powders, granules, liquids, particles, rods, plates, blocks, solids, rounds, pastes, creams, caplets, gels, chewable tablets, and sticks. Among these, tablets, capsules, powders, granules, and liquids are particularly preferred. Specific examples include supplements, packaged beverages filled in PET bottles, cans, jars, etc., instant beverages to be dissolved in water (hot water), milk, fruit juice, green juice, etc., and food additives. These are preferred because they are easy to drink during meals and can enhance palatability.

[0034] The content of chitosan and other materials (components of the present invention) in the composition of the present invention may be appropriately determined within the range in which the effect is exhibited.

[0035] Generally, when the composition of the present invention is a pharmaceutical or supplement, the component of the present invention is preferably contained in an amount of 0.1 to 100 mass% of the total, calculated on a dry mass basis, more preferably 1 to 85 mass%, and even more preferably 5 to 70 mass%.

[0036] When the composition of the present invention is a packaged beverage, the component of the present invention is preferably contained in an amount of 0.0001 to 3 mass % of the total, more preferably 0.001 to 1 mass %, and even more preferably 0.01 to 0.5 mass %.

[0037] Furthermore, when the composition of the present invention is an instant beverage, the component of the present invention is contained in an amount of preferably 0.001 to 80 mass%, more preferably 0.005 to 70 mass%, and even more preferably 0.1 to 60 mass%, of the total amount calculated on a dry mass basis.

[0038] In order to more effectively exert the effects of the present invention, the components of the present invention preferably account for 80% or more of the total composition of the present invention, calculated on a dry mass basis, more preferably 90% or more, even more preferably 95% or more, and particularly preferably 100%.

[0039] The intake amount of the composition of the present invention is not particularly limited, but from the viewpoint of more significantly exhibiting the effects of the present invention, it is preferable that the daily intake amount of the component of the present invention is 10 mg / day or more, more preferably 100 mg / day or more, and even more preferably 800 mg / day or more. The composition of the present invention can be stored as a daily amount in a single container or divided into, for example, 2 to 3 containers so that the daily intake amount is the above-mentioned intake amount.

[0040] The blending mass ratio of chitosan to other materials, calculated on a dry mass basis, is preferably in the range of 0.5:1 to 2000:1, more preferably in the range of 0.75:1 to 1000:1, even more preferably in the range of 1:1 to 500:1, and particularly preferably in the range of 1:1 to 300:1. When the blending ratio of chitosan to other materials is in the above range, the effects of the present invention can be more effectively exhibited.

[0041] The composition of the present invention can be produced by known methods, if necessary, by adding ingredients other than the ingredients of the present invention. Examples of ingredients other than the ingredients of the present invention include vitamins such as water-soluble vitamins (vitamins B1, B2, B3, B5, B6, B12, B13, B15, B17, biotin, choline, folic acid, inositol, PABA, vitamin C, and vitamin P) and oil-soluble vitamins (vitamins A, D, E, and K); minerals such as calcium, magnesium, phosphorus, and iron; sulfur-containing compounds found in taurine and garlic; flavanoids or flavonoids such as hesperidin and quercetin; proteins such as collagen; peptides; amino acids; animal fats and oils; vegetable fats and oils; and ground products or extracts of animals and plants. [Example]

[0042] The present invention will be described below based on examples. (Sample preparation) To 6 mL of postprandial artificial intestinal fluid (FeSSIF: 15 mM sodium taurocholate, 3.75 mM lecithin, 144 mM acetic acid, 101 mM sodium hydroxide, 173 mM sodium chloride, pH 5.0) preheated to 37°C, the test substances were added at a 0.05% (W / V) concentration (chitosan 500 μg / mL, other materials 500 μg / mL, chitosan 450 μg / mL + other materials 50 μg / mL) and vortexed. The mixture was then heated in a 37°C water bath for 30 minutes with shaking at 100 rpm. As a control, 6 mL of postprandial artificial intestinal fluid was heated in a 37°C water bath for 30 minutes with shaking at 100 rpm.

[0043] After warming for 30 minutes, the mixture was centrifuged at 2000 rpm for 10 minutes.

[0044] 3 mL of the supernatant was taken without removing the precipitate (test substance), and an equal volume of ethyl acetate was added, followed by vortexing for 30 seconds. After vortexing, the mixture was centrifuged at 2000 rpm for 10 minutes.

[0045] The upper layer (1.5 mL) of the liquid was transferred to a new Falcon and evaporated to dryness using a centrifugal evaporator.

[0046] To the dried product, 600 μL of 2-propanol was added, and the mixture was subjected to ultrasonic waves for 10 minutes.

[0047] Thereafter, the mixture was centrifuged at 800 rpm for 3 minutes, and the supernatant was collected in a 1.5 mL tube to obtain a sample.

[0048] The following test substances were used: Chitosan used was an extract from crab. As the noni, sterilized crushed noni leaves were used. A 60% EtOH extract was used as chia seeds. A concentrated extract of fruit juice (squeezed fruit juice) was used as the olive. Roasted flaxseed powder was used. Resveratrol was extracted from grapes. The fucoidan used was purified powder of Okinawa mozuku seaweed. Commercially available lycopene, soybean isoflavones, nattokinase, cocoa polyphenols, octacosanol, and citrulline were used.

[0049] (Measurement of bile acid concentration) The bile acid concentration in the sample was measured using a Wako Total Bile Acid Test in the following manner.

[0050] 62.5 μL of enzyme solution was added to 25 μL of sample, mixed well, and then heated at 37°C for 10 minutes. 62.5 μL of reaction stop solution was then added, mixed well, and the absorbance at 560 nm was measured. 62.5 μL of blank enzyme solution was added to 25 μL of sample, and the reaction was carried out in the same manner to serve as a sample blank.

[0051] 62.5 μL of enzyme solution was added to 25 μL of aqueous propanol solution adjusted to 10, 20, 30, 40, or 50 μmol / L of 2-propanol, mixed well, and then heated at 37°C for 10 minutes. 62.5 μL of reaction stop solution was then added, mixed well, and the absorbance at 560 nm was measured to create a calibration curve. 25 μL of aqueous propanol solution adjusted to 10 μmol / L of 2-propanol was also added to 62.5 μL of blank enzyme solution, and the reaction was carried out in the same manner. This was used as a standard blank.

[0052] The bile acid concentration (µmol / L) of the sample was calculated from the calibration curve, and the relative value (%) was calculated with the control set at 100%.

[0053] The results are shown in Figures 1 to 12. Each figure shows the results for each added component: "chitosan alone," "other material alone," and "chitosan + other material added." The concentration units for added components are μg / mL in all graphs. The vertical axis shows the bile acid binding rate (the percentage of bile acids adsorbed in the control (100%)).

[0054] As shown in Figures 1 to 12, the bile acid binding rate was synergistically improved by combining chitosan with specific materials. Therefore, it can be seen that the effect of suppressing the rise in blood cholesterol levels by inhibiting cholesterol absorption in the body is dramatically improved by combining chitosan with specific materials.

[0055] [Example 2] (Production of tablets) Five tablets (250 mg) consisting of the following ingredients were prepared.

[0056] Chitosan 70% Resveratrol 0.5% Cocoa polyphenols 0.5% Lycopene 0.5% Calcium stearate 2% Silicon dioxide 2% Reduced maltose 24.5% [Example 3] (Production of tablets) Three tablets (350 mg) consisting of the following ingredients were prepared.

[0057] Chitosan 86% Soy isoflavones 1% Nattokinase 1% Octacosanol 1% Sucrose fatty acid ester 7% Reduced maltose 3% Pullulan 1%

[0058] The tablets are taken once or two or three times a day with water.

[0059] [Example 4] (Production of capsules) The following mixture was encapsulated in a hard capsule to prepare a capsule formulation (300 mg).

[0060] Chitosan 40% Resveratrol 1% Lycopene 1% Soy isoflavones 1% Noni leaf 1% Chia seeds 1% Olive juice extract 1% Nattokinase 1% Cocoa polyphenols 1% Flaxseed 1% Octacosanol 1% Fucoidan 1% Citrulline 1% Lactic acid bacteria 10% Cellulose 36% Silicon dioxide 2%

[0061] Take 4 capsules of the above with water once a day or in 2 to 4 divided doses.

[0062] [Example 5] (Production of Granules) The following ingredients were mixed and prepared into granules (3000 mg) in a conventional manner.

[0063] Chitosan 10% Citrulline 10% Aspartame 5% Thiamine hydrochloride 0.33% Riboflavin 0.33% Vitamin B6 0.17% Cyanocobalamin 6 0.17% Fragrance 0.17% Reduced Palatinose 6.67% Calcium stearate 3.33% Hydroxypropyl cellulose Remainder

[0064] [Example 6] (Production of instant powder) The following ingredients were mixed together to prepare an instant powder (2 g) in a conventional manner.

[0065] Chitosan 50% Fucoidan 5% Olive juice extract 5% Aspartame 8% Stevia 3% Malic acid 0.5% Pigment preparation 0.5% Fragrance 0.25% Polydextrose Remainder

[0066] [Example 7] (Production of liquid preparation) A liquid formulation (200 mL) consisting of the following components was prepared.

[0067] Chitosan 0.62% Noni leaf 0.05% Chia seeds 0.05% Flaxseed 0.05% Pu'er tea processed food 0.13% Jasmine tea processed food 0.15% Fructooligosaccharides 0.075% Vitamin C 0.25% Water remaining [Industrial Applicability]

[0068] The composition of the present invention has the effect of suppressing an increase in blood cholesterol and is therefore highly useful industrially.

Claims

[Claim 1] Chitosan and A composition for suppressing an increase in blood cholesterol, characterized by containing lycopene.

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