JP2022050660A - Blood cholesterol rise inhibitory composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition with a blood cholesterol rise inhibitory action dramatically improved.

SOLUTION: A composition contains chitosan, and at least one material selected from the group consisting of the following (a)-(b): (a) at least one functional material selected from resveratrol, lycopene, soybean isoflavone, nattokinase, cacao polyphenol, octacosanol, fucoidan and citrulline; (b) at least one plant material selected from leaves of Morinda citrifolia, seeds of Salvia hispanica, fruits of Olea europaea, and seeds of Linum usitatissimum.

SELECTED DRAWING: Figure 1

COPYRIGHT: (C)2022,JPO&INPIT

Description

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 containing chitosan and a specific material.

Chitosan is known to have various functions of adjusting the condition of the body, and one of them is known to have an action of suppressing an increase in blood cholesterol. However, its single action and effect are not always sufficient.

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

Japanese Unexamined Patent Publication No. 2009-120502 Japanese Unexamined Patent Publication No. 2005-075957

An object of the present invention is to provide a composition having a dramatically improved action of suppressing an increase in blood cholesterol.

As a result of diligent research and research on the inhibitory effect of chitosan on blood cholesterol elevation, the present inventors have found that the combination of chitosan and a specific material can synergistically improve the blood cholesterol elevation inhibitory effect. , The present invention has been completed.

That is, the present invention is as follows.
[1] A composition for suppressing an increase in blood cholesterol, which comprises 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, soy isoflavone, nuttokinase, cocoa polyphenols, octacosanol, fucoidan and citrulin (b) selected from noni leaves, chia seeds, olive fruits and flaxseed The composition according to [1], wherein at least one plant material [2] is in the form of a tablet, a capsule, a powder, a granule, or a liquid.
[3] The composition according to [1] or [2], which is characterized by being a food composition.

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

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

The composition of the present invention is characterized by containing chitosan and at least one material (hereinafter, may be referred to as another material) selected from the group consisting of the following (a) to (b). The materials (a) to (b) 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 chitosan and other materials having a high synergistic effect.

According to the composition of the present invention, the combination of chitosan and a specific material can synergistically improve the effect of suppressing the increase of blood cholesterol (LDL cholesterol). Therefore, the composition of the present invention also helps prevent arteriosclerosis.

[Chitosan]
The chitosan used in the composition of the present invention is a basic dietary fiber having an amino group, and is obtained from, for example, shells such as crabs, shrimp and insects, and cell walls such as mushrooms and filamentous fungi. Examples include those obtained from the middle bone (cartilage) of squid. Among these, those obtained from crabs, shrimp and the like are preferable. The chitosan of the present invention may have chitin remaining 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 crushed, and the crushed shells are treated with an acid such as hydrochloric acid to decalcify. Next, chitin is obtained by treating with an alkali such as caustic soda to remove the protein. Further, by treating this with an alkali such as caustic soda, chitosan can be obtained.

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

(Resveratrol)
The resveratrol of the present invention is not particularly limited as long as it is a kind of stilbenoid (stilbene derivative) polyphenol and the strain name is 3,5,4'-trihydroxy-trans-stilbene. Resveratrol is found in natural products such as vines, apple berries, cowberries and Indian mushroom trees. In the composition of the present invention, such a processed product of a natural product (dried product, crushed product, squeezed 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 whose chemical formula is represented by C ₄₀ H ₅₆ (molecular weight 536.87). Lycopene belongs to a kind of carotenoid carotene, is a red pigment showing a maximum absorption at 474 nm (acetone), and is known to have an extremely high antioxidant effect and whitening effect. Lycopene contains cis and trans isomers of conjugated double bonds in the center of the molecule, such as whole trans-form, 9-cis and 13-cis isomers. Be done. In the present invention, the lycopene may be any of the above.

Lycopene is naturally found in natural products such as tomatoes, persimmons, watermelons and pink grapefruits. In the composition of the present invention, such a processed product of a natural product (dried product, crushed product, squeezed juice, extract, purified product, etc.) may be used, or a chemically synthesized product may be used.

(Soy isoflavone)
Soybean 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. Further, in the composition of the present invention, the soybean isoflavone may be purified, but a processed soybean product (dried product, crushed product, squeezed 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, the nattokinase may be purified, but a processed product of natto (dried product, crushed product, squeezed juice, extract, etc.) may be used.

(Cacao polyphenols)
Cacao polyphenols are polyphenols contained in cocoa beans, which are raw materials for chocolate and cocoa, and are a mixture of epicatechins and compounds mainly composed of catechins (flavanols). In the composition of the present invention, the cacao polyphenol may be purified, but a processed product of cacao beans (dried product, crushed product, squeezed juice, extract, etc.) may be used.

(Octacosanol)
Octacosanol, also called octacosyl alcohol, is an alcohol contained in the leaves of plants and the skins of fruits such as apples and grapes. In the composition of the present invention, such a processed product of a natural product (dried product, crushed product, squeezed 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 it, and is known to have an anticancer effect, an antiulcer effect, and a cholesterol lowering effect. Fucoidan is contained in seaweed, kelp, wakame seaweed, mozuku seaweed, and hijiki seaweed. Among them, fucoidan has a high content in gagome kelp and mozuku seaweed, and is preferably used in the present invention. In the composition of the present invention, such a processed product of a natural product (dried product, crushed product, squeezed juice, extract, purified product, etc.) may be used, or a chemically synthesized product may be used.

(Citrulline)
The citrulline of the present invention may be L-citrulline or D-citrulline, but L-citrulline is preferable. Citrulline may be produced by chemical synthesis, fermentation, etc., regardless of the production method. Further, the citrulin may be in the form of a salt, and the salt is not particularly limited as long as it is a pharmaceutically acceptable salt. For example, an inorganic acid salt, an organic acid salt, a metal salt, or an ammonium salt is used. You can mention salt.

(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 plant processed products such as dried plants, crushed products, squeezed juices, and extracts. Examples of the crushed product include powder, granules and the like. The squeezed juice and the extract may be liquid, but can also be used as a paste or a dry powder. The extract can be obtained by extracting with an appropriate solvent, and as the solvent, for example, water (hot water, hot water), ethanol, or hydrous ethanol can be used. As the plant material, a commercially available one may be used.

(Noni leaf)
Noni is an evergreen small tree of the genus Noni in the family Rubiaceae, and is also called Noni (Yaeyama Aoki). The scientific name is Morinda citrifolia. In the present invention, it is preferable to use a crushed noni leaf.

(Chia seeds)
Chia is an annual plant of the genus Sage in the Labiatae family, and its scientific name is Salvia hispanica. Chia seeds, which are chia seeds, are rich in Ω-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 tree of the family Oleaceae, and its scientific name is Olea europaea. Olive fruits contain healthy ingredients such as oleic acid and vitamin E, and are used in 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 appropriately concentrated and used.

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

The composition of the present invention has an effect of suppressing an increase in blood cholesterol, and is, for example, from a predetermined organization such as a pharmaceutical product (including non-pharmaceutical products), a food for specified health use, a food with nutritional function, and a food with functional claims. It can be used as so-called health foods such as functional foods whose efficacy has been approved, general foods, food additives, feeds and the like.

The composition of the present invention can be used as a composition for suppressing an increase in blood cholesterol used for suppressing an increase in blood cholesterol, and the food for suppressing an increase in blood cholesterol contains chitosan and a predetermined material. The product is not particularly limited as long as it can be distinguished from other products in that it is used for suppressing the increase in blood cholesterol. The scope of the present invention includes any of the advertisements indicating that the product has a function of suppressing the increase in blood cholesterol. In the composition for suppressing the increase in blood cholesterol of the present invention, the components of the combination in the present invention (chitosan and other predetermined materials) are displayed as active ingredients for suppressing the increase in blood cholesterol on the packaging of the product or the like. Not limited to things. For example, the active ingredient may not be specified, or only chitosan may be displayed as the active ingredient.

Specific examples of the composition for suppressing the increase in blood cholesterol of the present invention include pharmaceuticals (including quasi-drugs) and so-called health foods. In so-called health foods, "suppressing the increase in cholesterol" and " Examples include those labeled as "for those who are concerned about cholesterol", "for those who suppress the absorption of cholesterol", and "for those who have high cholesterol".

The form of the composition of the present invention includes, for example, tablets, capsules, powders, granules, liquids, granules, rods, plates, blocks, solids, rounds, pastes, creams, and caplets. , Gel-like, chewable-like, stick-like and the like. Among these, tablet-like, capsule-like, powder-like, granular, and liquid forms are particularly preferable. Specifically, supplements, packaged beverages filled in PET bottles, cans, bottles, etc., instant beverages for dissolving in water (hot water), milk, fruit juice, green juice, etc., and food additives. Can be exemplified. These are preferable in that they are easy to drink at the time of meals and can enhance the palatability.

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

Generally, when the composition of the present invention is a pharmaceutical product or a supplement, it is preferable that the component of the present invention is contained in an amount of 0.1 to 100% by mass in terms of dry mass, and 1 to 85% by mass. It is more preferably contained, and further 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 3% by mass, preferably 0.001 to 1% by mass. More preferably, it is further preferably contained in an amount of 0.01 to 0.5% by mass.

When the composition of the present invention is an instant beverage, the component of the present invention is preferably contained in an amount of 0.001 to 80% by mass, preferably 0.005 to 70% by mass, in terms of dry mass. It is more preferable that it is contained, and it is further preferable that it is contained in an amount of 0.1 to 60% by mass.

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

The intake amount of the composition of the present invention is not particularly limited, but from the viewpoint of exerting the effect of the present invention more remarkably, the intake amount of the component of the present invention per day is 10 mg / day or more. It is more preferable to take it so as to be 100 mg / day or more, and it is further more preferable to take it so as to be 800 mg / day or more. The composition of the present invention can be contained in one container or divided into a plurality of containers, for example, 2 to 3 so that the daily intake becomes the above-mentioned intake, and can be contained as one day's worth.

The compounding mass ratio of chitosan and other materials is preferably in the range of 0.5: 1 to 2000: 1, and more preferably in the range of 0.75: 1 to 1000: 1 in terms of dry mass. It is 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 and other materials is within the above range, the effect of the present invention can be more effectively exhibited.

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

Hereinafter, the present invention will be described based on examples.
(Sample preparation)
0.05% of the test substance (FeSSIF: 15 mM sodium taurocorate, 3.75 mM lecithin, 144 mM acetic acid, 101 mM sodium hydroxide, 173 mM sodium chloride, pH 5.0) to 6 mL of postprandial artificial intestinal juice warmed to 37 ° C. W / V) concentration (“chitosan 500 μg / mL” “other material 500 μg / mL” “chitosan 450 μg / mL + other material 50 μg / mL”) was added and vortexed. Then, it was warmed in a water bath at 37 ° C. for 30 minutes while shaking at 100 rpm. As a control, 6 mL of postprandial artificial intestinal juice was warmed in a water bath at 37 ° C. for 30 minutes while shaking at 100 rpm.

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

3 mL of the supernatant was taken so as not to absorb the precipitate (test substance), an equal amount of ethyl acetate was added, and the mixture was vortexed for 30 seconds. After vortexing, it was centrifuged at 2000 rpm for 10 minutes.

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

600 μL of 2-propanol was added to the dry matter, and the mixture was sonicated for 10 minutes.

Then, it was centrifuged at 800 rpm for 3 minutes, and the supernatant was collected in a 1.5 mL tube to obtain a sample.

The following substances were used as various test substances.
An extract from crab was used as chitosan.
As noni, a noni leaf sterilized crushed product was used.
A 60% EtOH extract was used as the chia seeds.
As olive, a concentrated extract of fruit juice (fruit juice) was used.
Roasted powder was used as flaxseed.
An extract from grapes was used as resveratrol.
As fucoidan, purified powder of Okinawa mozuku was used.
Commercially available products were used for lycopene, soybean isoflavone, nattokinase, cacao polyphenol, octacosanol and citrulline.

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

62.5 μL of the enzyme solution was added to 25 μL of the sample, mixed well, and then heated at 37 ° C. for 10 minutes. Then, 62.5 μL of the reaction terminator was added, mixed well, and the absorbance at 560 nm was measured. Further, 25 μL of the sample to which 62.5 μL of the blind enzyme solution was added was also reacted in the same manner to prepare a blank of the sample.

62.5 μL of the enzyme solution was added to 25 μL of the propanol aqueous solution whose concentration of 2-propanol was adjusted to 10, 20, 30, 40 and 50 μmol / L, and the mixture was well mixed and then heated at 37 ° C. for 10 minutes. Then, 62.5 μL of the reaction terminator was added, mixed well, and the absorbance at 560 nm was measured to prepare a calibration curve. Further, 25 μL of a propanol aqueous solution adjusted to a concentration of 2-propanol to 10 μmol / L and 62.5 μL of a blind enzyme solution were also reacted in the same manner, and this was used as a blank of the standard solution.

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

The results are shown in FIGS. 1 to 12. Each figure shows the results of "single addition of chitosan", "single addition of other materials", and "addition of chitosan + other materials" for each added component. The concentration unit of the additive component is μg / mL in all graphs. The vertical axis shows the bile acid binding rate (what percentage of the bile acid in the control (100%) was adsorbed).

As shown in FIGS. 1 to 12, the combination of chitosan and a specific material synergistically improved the bile acid binding rate. Therefore, it can be seen that the combination of chitosan and a specific material dramatically improves the effect of suppressing the increase in blood cholesterol by inhibiting the absorption of cholesterol in the body.

[Example 2] (Manufacturing of tablets)
Five tablets (250 mg) consisting of the following ingredients were produced.

Chitosan 70%
Resveratrol 0.5%
Cacao polyphenol 0.5%
Lycopene 0.5%
Calcium stearate 2%
Silicon dioxide 2%
Reduced maltose 24.5%
[Example 3] (Manufacturing of tablets)
Three tablets (350 mg) consisting of the following ingredients were produced.

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

The above tablets should be taken with water once or divided into two or three times a day.

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

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

The above capsules are taken in 4 capsules once a day or in 2 to 4 divided doses with water.

[Example 5] (Production of granules)
The following components were mixed to prepare 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%
Hirodoxypropyl Cellulose Remaining

[Example 6] (Manufacturing 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 remnants

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

Chitosan 0.62%
Noni leaf 0.05%
Chia seeds 0.05%
Flax 0.05%
Pu'er tea processed food 0.13%
Jasmine tea processed food 0.15%
Fructooligosaccharide 0.075%
Vitamin C 0.25%
Remaining water

Since the composition of the present invention has an action of suppressing an increase in cholesterol in blood, it is highly industrially useful.

Claims (3)

A composition for suppressing an increase in blood cholesterol, which comprises 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 lycopene, soy isoflavone, nattokinase, cocoa polyphenols, octacosanol, fucoidan and citrulin (b) At least one selected from noni leaves, chia seeds, olive fruits, and flaxseed Plant material The composition according to claim 1, wherein the composition is in the form of a tablet, a capsule, a powder, a granule, or a liquid. The composition according to claim 1 or 2, characterized in that it is a food composition.

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