JP2019001763A - Blood cholesterol rise inhibitory composition - Google Patents

Abstract

An object of the present invention is to provide a composition in which the blood cholesterol elevation-inhibiting action is dramatically improved. A composition containing chitosan and at least one material selected from the group consisting of the following (a) to (b). (A) at least one functional material selected from resveratrol, lycopene, soybean isoflavone, nattokinase, cacao polyphenol, octacosanol, fucoidan and citrulline (b) selected from noni leaf, chia seed, olive fruit, and flaxseed At least one plant material [selection] Figure 1

Description

  The present invention relates to a composition having an inhibitory action on blood cholesterol elevation, and more specifically, relates to a composition having an inhibitory action on blood cholesterol elevation containing chitosan and a specific material.

  Chitosan is known to have various functions for adjusting the physical condition of the body, and as one of them, it is known to have an action of suppressing an increase in blood cholesterol. However, it cannot be said that the single effect is sufficient.

  Moreover, regarding other functions of chitosan, for example, serum uric acid level improving action (see Patent Document 1) and antioxidant action (see Patent Document 2) have been reported.

JP 2009-120502 A Japanese Patent Laying-Open No. 2005-079557

  The subject of this invention is providing the composition which the blood cholesterol raise inhibitory effect improved dramatically.

  As a result of diligent investigation and research on the blood cholesterol increase inhibitory action of chitosan, the present inventors have found that the blood cholesterol increase inhibitory action can be synergistically improved by combining chitosan and a specific material. The present invention has been completed.

That is, the present invention is as follows.
[1] A composition for suppressing blood cholesterol elevation, comprising chitosan and at least one material selected from the group consisting of the following (a) to (b).
(A) At least one functional material selected from resveratrol, lycopene, soybean isoflavone, nattokinase, cacao polyphenol, octacosanol, fucoidan and citrulline (b) selected from noni leaf, chia seed, olive fruit, and flaxseed The composition according to [1], wherein the composition is at least one plant material [2] in the form of a tablet, capsule, powder, granule, or liquid.
[3] The composition according to [1] or [2], which is a food composition.

  According to the composition of the present invention, the blood cholesterol elevation inhibitory action can be synergistically improved by the combination of chitosan and a specific material.

It is a figure which shows the blood cholesterol raise inhibitory effect (bile acid binding rate) of the composition (chitosan + resveratrol) of this invention. It is a figure which shows the blood cholesterol raise inhibitory effect (bile acid binding rate) of the composition (chitosan + lycopene) of this invention. It is a figure which shows the blood cholesterol raise inhibitory effect (bile acid binding rate) of the composition (chitosan + soybean isoflavone) of this invention. It is a figure which shows the blood cholesterol raise inhibitory effect (bile acid binding rate) of the composition (chitosan + nattokinase) of this invention. It is a figure which shows the blood cholesterol raise inhibitory effect (bile acid binding rate) of the composition (chitosan + cacao polyphenol) of this invention. It is a figure which shows the blood cholesterol raise inhibitory effect (bile acid binding rate) of the composition (chitosan + octacosanol) of this invention. It is a figure which shows the blood cholesterol raise inhibitory effect (bile acid binding rate) of the composition (chitosan + fucoidan) of this invention. It is a figure which shows the blood cholesterol raise inhibitory effect (bile acid binding rate) of the composition (chitosan + citrulline) of this invention. It is a figure which shows the blood cholesterol raise inhibitory effect (bile acid binding rate) of the composition (chitosan + noni leaf) of this invention. It is a figure which shows the blood cholesterol raise inhibitory effect (bile acid binding rate) of the composition (chitosan + chia seed) of this invention. It is a figure which shows the blood cholesterol raise inhibitory effect (bile acid binding rate) of the composition (chitosan + olive fruit) of this invention. It is a figure which shows the blood cholesterol raise inhibitory effect (bile acid binding rate) of the composition (chitosan + flaxseed) of this invention.

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

  According to the composition of this invention, the raise inhibitory effect of blood cholesterol (LDL cholesterol) can be improved synergistically by the combination of chitosan and a specific raw material. Therefore, the composition of the present invention is also useful for preventing arteriosclerosis.

[Chitosan]
Chitosan used in the composition of the present invention is a basic dietary fiber having an amino group, for example, obtained from a shell such as crab, shrimp or insect, or from a cell wall such as mushroom or filamentous fungus. And those obtained from the middle bones (cartilage) of squid. Among these, those obtained from crabs, shrimps and the like are preferable. The chitosan of the present invention may be one in which chitin remains in the chitosan chain, or may be a salt.

  Chitosan can be obtained, for example, by the following method. First, crab shells, shrimp shells and the like are pulverized, and the crushed shells are treated with an acid such as hydrochloric acid to perform decalcification. Next, chitin is obtained by treating with an alkali such as caustic soda to remove proteins. Furthermore, chitosan is obtained by treating this with an alkali such as caustic soda.

[Other materials]
(A) Functional material In the composition of the present invention, together with chitosan, at least one functional material selected from resveratrol, lycopene, soybean isoflavone, nattokinase, cacaopolyphenol, octacosanol, fucoidan and citrulline may be used. preferable.

(Resveratrol)
The resveratrol of the present invention is not particularly limited as long as it is a compound that is a kind of stilbenoid (stilbene derivative) polyphenol and whose system name is 3,5,4′-trihydroxy-trans-stilbene. Resveratrol is contained in natural products such as grapes, apple berries, cowberry and Indian mushrooms. In the composition of the present invention, such a processed product of natural product (dried product, pulverized product, juice, extract, purified product, etc.) may be used, or a chemically synthesized product may be used.

(Lycopene)
The lycopene of the present invention is not particularly limited as long as it is a carotenoid represented by the chemical formula C ₄₀ H ₅₆ (molecular weight 536.87). Lycopene belongs to a kind of carotenoids of carotenoids and is a red pigment having an absorption maximum at 474 nm (acetone), and is known for its extremely high antioxidant effect and whitening effect. In lycopene, there are cis and trans isomers of a conjugated double bond at the center of the molecule. Examples of such lycopene include all-trans-forms, 9-cis-forms and 13-cis-forms. It is done. In the present invention, the lycopene may be any of those described above.

  In nature, lycopene is contained in natural products such as tomatoes, strawberries, watermelons, and pink grapefruits. In the composition of the present invention, such a processed product of natural product (dried product, pulverized product, juice, extract, purified product, etc.) may be used, or a chemically synthesized product may be used.

(Soybean isoflavone)
Soy isoflavone is a kind of flavonoid mainly contained in soybean germ. The soybean isoflavone in the present invention may be an aglycone or a glycoside. In the composition of the present invention, the soybean isoflavone may be purified, but a soybean processed product (dried product, pulverized product, juice, extract, etc.) may be used.

(Nattokinase)
Nattokinase is an enzyme purified from Bacillus subtilis var. Natto contained in natto. In the composition of the present invention, nattokinase may be purified, or a processed product of natto (dried product, pulverized product, juice, extract, etc.) may be used.

(Cocoa polyphenol)
Cacao polyphenol is a polyphenol contained in cocoa beans, which are raw materials for chocolate and cocoa, and is a mixture (flavanol) of compounds mainly composed of epicatechin and catechin. In the composition of the present invention, the cocoa polyphenol may be purified, or a processed product (dried product, pulverized product, juice, extract, etc.) of cocoa beans may be used.

(Octacosanol)
Octacosanol is also called octacosyl alcohol, and is an alcohol contained in the leaves of plants, fruit peels such as apples and grapes. In the composition of the present invention, such a processed product of natural product (dried product, pulverized product, juice, extract, purified product, etc.) may be used, or a chemically synthesized product may be used.

(Fucoidan)
Fucoidan is a polysaccharide in which fucose is the main constituent sugar and sulfuric acid or uronic acid is bound to this, and is known to have anticancer action, antiulcer action, and cholesterol lowering action. Fucoidan is contained in seaweed, kelp, seaweed, mozuku, and hijiki. Among them, gagome kelp and mozuku have a high content and are preferably used in the present invention. In the composition of the present invention, such a processed product of natural product (dried product, pulverized product, juice, extract, purified product, etc.) may be used, or a chemically synthesized product may be used.

(Citrulline)
Citrulline of the present invention may be L-citrulline or D-citrulline, but is preferably L-citrulline. Citrulline is not limited in its production method, such as those obtained by chemical synthesis and those obtained by fermentation. Citrulline may be in the form of a salt, and the salt is not particularly limited as long as it is a pharmaceutically acceptable salt. Examples thereof include inorganic acid salts, organic acid salts, metal salts, ammonium salts. Mention may be made of salts.

(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 flaxseed together with chitosan.

  These plant materials are preferably used as processed plant products such as dried plants, ground products, juices, and extracts. Examples of the pulverized product include powder and granules. The squeezed juice or extract may be liquid, but can also be used as a paste or dry powder. The extract can be obtained by extraction using an appropriate solvent, and as the solvent, for example, water (warm water, hot water), ethanol, hydrous ethanol can be used. As the plant material, commercially available products may be used.

(Noni leaves)
Noni is an evergreen small Takagi of the genus Ryeaceae, Ayayama Aoki (Yaeyama Aoki). The scientific name is Morinda citrifolia. In the present invention, it is preferable to use a ground noni leaf.

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

(Olive fruit)
Olive is an evergreen Takagi of the aceae family and its scientific name is Olea europaea. The fruits of olives contain health ingredients such as oleic acid and vitamin E, and are used for the production of olive oil and pickles. In the present invention, it is preferable to use fruit juice obtained by squeezing olive fruit, and it can be used after being appropriately concentrated.

(linseed)
Flax is an annual plant of flaxaceae and its scientific name is Linum usitatissimum. Flaxseed is a seed of flax and is rich in α-linolenic acid, lignan and dietary fiber, and has a strong antioxidant power. In the present invention, it is preferable to use a pulverized linseed.

  The composition of the present invention has an inhibitory effect on blood cholesterol elevation. For example, the composition of the present invention includes pharmaceuticals (including quasi-drugs), foods for specified health use, nutritional functional foods, functional indication foods and the like It can be used as so-called health foods such as functional foods for which indication of efficacy is recognized, general foods, food additives, feeds and the like.

  The composition of the present invention can be used as a composition for suppressing blood cholesterol elevation used for suppressing blood cholesterol elevation, and the food for suppressing blood cholesterol elevation contains chitosan and a predetermined material. In terms of being used for suppressing blood cholesterol elevation, it is not particularly limited as long as it can be distinguished from other products as a product. For example, the product body, packaging, instructions, Any advertisement that indicates that it has a function of suppressing blood cholesterol elevation is included in the scope of the present invention. In the composition for suppressing blood cholesterol elevation according to the present invention, the components of the combination according to the present invention (chitosan and other predetermined materials) are displayed as active ingredients for suppressing blood cholesterol elevation in product packaging and the like. It is not limited to things. For example, the active ingredient may not be specified, or only chitosan may be displayed as the active ingredient.

  Specifically, the composition for suppressing blood cholesterol elevation of the present invention includes pharmaceuticals (including quasi-drugs) and so-called health foods. In so-called health foods, “suppressing cholesterol elevation”, “ Examples of the indications such as “to those who are concerned about cholesterol”, “suppress cholesterol absorption”, “to those who have higher cholesterol”, and the like can be given.

  Examples of the composition of the present invention include tablets, capsules, powders, granules, liquids, granules, rods, plates, blocks, solids, rounds, pastes, creams, caplets , Gel, chewable, stick and the like. Among these, a tablet, capsule, powder, granule, and liquid form are particularly preferable. Specifically, supplements, container-packed beverages filled in PET bottles, cans, bottles, instant beverages that are dissolved in water (hot water), milk, fruit juice, green juice, etc., and food additives Can be illustrated. These are preferable in that they can be easily taken at the time of eating and the like, and can enhance palatability.

  The contents of chitosan and other materials (components of the present invention) in the composition of the present invention may be appropriately contained within the range where the effects are exerted.

  In general, when the composition of the present invention is a pharmaceutical product or a supplement, the component of the present invention is preferably contained in an amount of 0.1 to 100% by mass in terms of dry mass, and 1 to 85% by mass. More preferably, it is contained more preferably 5 to 70% by mass.

  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 1% by mass, and 0.001 to 1% by mass is contained. More preferably, it is more preferably 0.01 to 0.5% by mass.

  Moreover, when the composition of this invention is an instant drink, it is preferable that the component of this invention is contained 0.001-80 mass% of the whole in conversion of dry mass, 0.005-70 mass% is contained. It is more preferable that 0.1 to 60% by mass is contained.

  In order to exhibit the effect of the present invention more effectively, the component of the present invention is preferably contained in an amount of 80% or more of the entire composition of the present invention in terms of dry mass, and 90% or more is contained. More preferably, it is more preferably 95% or more, and particularly preferably 100%.

  Although there is no restriction | limiting in particular as intake of the composition of this invention, it is ingested so that the intake of the component of this invention per day may be 10 mg / day or more from a viewpoint of exhibiting the effect of this invention more notably. It is preferable to take it so that it is 100 mg / day or more, and it is more preferable to take it so that it is 800 mg / day or more. The composition of the present invention can be accommodated in one container or divided into a plurality of containers such as 2 to 3 so that the daily intake becomes the above-mentioned intake.

  The mixing mass ratio of chitosan and other materials is preferably in the range of 0.5: 1 to 2000: 1, more preferably in the range of 0.75: 1 to 1000: 1, in terms of dry mass. The range of 1: 1 to 500: 1 is more preferable, and the range of 1: 1 to 300: 1 is particularly preferable. The effect of this invention can be exhibited more effectively because the compounding ratio of chitosan and other materials is in the above range.

  The composition of this invention can be manufactured by a well-known method, adding other components other than the component of this invention as needed. Other components other than the components of the present invention include, for example, water-soluble vitamins (vitamins B1, B2, B3, B5, B6, B12, B13, B15, B17, biotin, choline, folic acid, inositol, PABA, vitamin C, Vitamin P), vitamins such as oil-soluble vitamins (vitamins A, D, E, K); minerals such as calcium, magnesium, phosphorus, iron; sulfur-containing compounds contained in taurine, garlic, etc .; hesperidin, quercetin, etc. Examples include flavanoids or flavonoids; proteins such as collagen; peptides; amino acids; animal fats and oils; vegetable oils and fats;

Hereinafter, the present invention will be described based on examples.
(Sample preparation)
0.05% (6%) of test substance against 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) warmed to 37 ° C. W / V) concentrations (“chitosan 500 μg / mL” “other materials 500 μg / mL” “chitosan 450 μg / mL + other materials 50 μg / mL”) were added and vortexed. Then, it warmed, shaking at 100 rpm for 30 minutes with a 37 degreeC water bath. As a control, 6 mL of postprandial artificial intestinal fluid was warmed by shaking at 100 rpm for 30 minutes in a 37 ° C. water bath.

  After warming for 30 minutes, it was centrifuged at 2000 rpm for 10 minutes.

  To prevent the precipitate (test substance) from being sucked out, 3 mL of the supernatant was taken, an equal amount of ethyl acetate was added, and vortexed for 30 seconds. After vortexing, the mixture was centrifuged at 2000 rpm for 10 minutes.

  1.5 mL of the upper layer of the liquid was transferred to a new falcon and dried using a centrifugal evaporator.

  To the dried product, 600 μL of 2-propanol was added and sonicated for 10 minutes.

  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.

In addition, the following were used as various test substances.
As chitosan, an extract from crab was used.
Noni leaf sterilized pulverized product was used as noni.
As a chia seed, 60% EtOH extract was used.
As the olive, a concentrated extract of fruit juice (fruit juice) was used.
Roasted powder was used as flaxseed.
As resveratrol, an extract from grapes was used.
As fucoidan, a purified powder of Okinawa mozuku was used.
Commercial products were used for lycopene, soybean isoflavone, nattokinase, cacao polyphenol, octacosanol and citrulline.

(Measurement of bile acid concentration)
Using total bile acid test Wako, the bile acid concentration in the sample was measured by the following method.

  62.5 μL of enzyme solution was added to 25 μL of the sample and mixed well, followed by heating at 37 ° C. for 10 minutes. Thereafter, 62.5 μL of a reaction stop solution was added and mixed well, and the absorbance at 560 nm was measured. Moreover, what added 62.5 microliters of enzyme solutions for blind to 25 microliters of samples was made to react similarly, and it was set as the sample blank.

  62.5 μL of an enzyme solution was added to 25 μL of a propanol aqueous solution adjusted to a concentration of 2-propanol of 10, 20, 30, 40, 50 μmol / L, mixed well, and then heated at 37 ° C. for 10 minutes. Thereafter, 62.5 μL of the reaction stop solution was added and mixed well, and the absorbance at 560 nm was measured to prepare a calibration curve. Moreover, what added 62.5 microliters of enzyme solutions for blind to 25 microliters of propanol aqueous solution which adjusted the density | concentration of 2-propanol to 10 micromol / L was made to react similarly, and it was set as the blank of standard solution.

  From the calibration curve, the bile acid concentration (μmol / L) of the sample was calculated, and the relative value (%) when the control was 100% was calculated.

  The results are shown in FIGS. Each figure shows the results of “single addition of chitosan”, “single addition of other materials”, and “addition of chitosan + other materials” for each additive component. The concentration unit of the additive component is μg / mL in all graphs. The vertical axis shows the bile acid binding rate (how many of the bile acids in the control (100%) were adsorbed).

  As shown in FIGS. 1 to 12, the bile acid binding rate was synergistically improved by combining chitosan and a specific material. Therefore, it can be seen that by combining chitosan and a specific material, the blood cholesterol elevation suppressing effect due to inhibition of cholesterol absorption in the body is dramatically improved.

[Example 2] (Manufacture of tablets)
Five tablets (250 mg) comprising the following components were produced.

Chitosan 70%
Resveratrol 0.5%
Cocoa polyphenol 0.5%
Lycopene 0.5%
Calcium stearate 2%
Silicon dioxide 2%
Reduced maltose 24.5%
Example 3 (Manufacture of tablets)
Three tablets (350 mg) comprising the following components were produced.

Chitosan 86%
Soy isoflavone 1%
Nattokinase 1%
Octacosanol 1%
Sucrose fatty acid ester 7%
Reduced maltose 3%
Pullulan 1%

  The tablet is taken with water once or twice or three times a day.

[Example 4] (Manufacture of capsules)
The following mixture was enclosed in a hard capsule to produce a capsule (300 mg).

Chitosan 40%
Resveratrol 1%
Lycopene 1%
Soy isoflavone 1%
Noni leaves 1%
Chia seed 1%
Olive juice extract 1%
Nattokinase 1%
Cocoa polyphenol 1%
Flaxseed 1%
Octacosanol 1%
Fucoidan 1%
Citrulline 1%
Lactic acid bacteria 10%
Cellulose 36%
Silicon dioxide 2%

  The above capsules are taken with 4 tablets once a day or divided into 2 to 4 times with water.

[Example 5] (Production of granules)
The following ingredients were mixed to produce granules (3000 mg) by a conventional method.

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%
Hydroxypropylcellulose remainder

[Example 6] (Production of instant powder)
The following ingredients were mixed to produce an instant powder (2 g) by a conventional method.

Chitosan 50%
Fucoidan 5%
Olive juice extract 5%
Aspartame 8%
Stevia 3%
Malic acid 0.5%
Dye preparation 0.5%
Fragrance 0.25%
Polydextrose balance

[Example 7] (Production of liquid preparation)
A liquid (200 mL) comprising the following components was produced.

Chitosan 0.62%
Noni leaves 0.05%
Chia seed 0.05%
Flaxseed 0.05%
Pu'er tea processed food 0.13%
Jasmine tea processed food 0.15%
Fructooligosaccharide 0.075%
Vitamin C 0.25%
Water remaining

  Since the composition of this invention has the effect | action which suppresses the raise of the cholesterol in blood, industrial usefulness is high.

Claims (3)

A composition for suppressing blood cholesterol elevation, comprising chitosan and at least one material selected from the group consisting of the following (a) to (b).
(A) At least one functional material selected from resveratrol, lycopene, soybean isoflavone, nattokinase, cacao polyphenol, octacosanol, fucoidan and citrulline (b) selected from noni leaf, chia seed, olive fruit, and flaxseed At least one plant material   The composition according to claim 1, wherein the composition is in the form of a tablet, capsule, powder, granule, or liquid.   The composition according to claim 1, wherein the composition is a food composition.