JP7793232B2 - Composition for suppressing blood cholesterol elevation - Google Patents

Description

The present invention relates to a composition that has the effect of suppressing an increase in blood cholesterol levels, and more specifically, to a composition that contains chitosan and a specific material and has the effect of suppressing an increase in blood cholesterol levels.

Chitosan is known to have various functions that help regulate the body, one of which is its ability to suppress the rise of blood cholesterol. However, this effect alone is not necessarily sufficient.

In addition, other functions of chitosan have been reported, such as its ability to improve serum uric acid levels (see Patent Document 1) and its antioxidant effect (see Patent Document 2).

JP 2009-120502 A Japanese Patent Application Laid-Open No. 2005-075957

The objective of the present invention is to provide a composition with dramatically improved blood cholesterol-increasing inhibitory effect.

As a result of extensive research and study into chitosan's ability to inhibit elevated blood cholesterol levels, the inventors discovered that combining chitosan with specific materials can synergistically improve the ability to inhibit elevated blood cholesterol levels, leading to the completion of this invention.

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 polyphenol, octacosanol, fucoidan, and citrulline; and (b) at least one plant material selected from noni leaves, chia seeds, olive fruit, and flaxseed. [2] The composition according to [1], which is in the form of a tablet, capsule, powder, granule, or liquid.
[3] The composition according to [1] or [2], which is a food composition.

The composition of the present invention, by combining chitosan with specific materials, can synergistically improve the effect of suppressing blood cholesterol elevation.

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). 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). FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan + soybean isoflavone). 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). FIG. 1 is a graph showing the blood cholesterol increase inhibitory effect (bile acid binding rate) of the composition of the present invention (chitosan + cocoa polyphenols). 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). 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). 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). 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). 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). 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). 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).

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) used together with chitosan may be used alone or in combination of two or more. When using a combination of two or more other materials, it is preferable to combine other materials that have a high synergistic effect with chitosan.

The composition of the present invention, combined with chitosan and specific materials, synergistically improves the effect of inhibiting increases in blood cholesterol (LDL cholesterol). Therefore, the composition of the present invention is also useful for preventing arteriosclerosis.

[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.

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, they are treated with an alkali such as caustic soda to remove proteins, yielding chitin. This is then further treated with an alkali such as caustic soda to yield chitosan.

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

(resveratrol)
The resveratrol of the present invention is not particularly limited as long as it is a type of stilbenoid (stilbene derivative) polyphenol and is a compound with 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, pulverized products, squeezed juice, extracts, purified products, etc.) of such natural products may be used, or chemically synthesized products may also 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 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-isomers, 9-cis isomers, and 13-cis isomers. In the present invention, the lycopene may be any of the above-mentioned isomers.

Lycopene is naturally found in natural products such as tomatoes, persimmons, watermelons, and pink grapefruit. The compositions of the present invention may use processed products of these natural products (dried products, crushed products, squeezed juice, extracts, purified products, etc.), or chemically synthesized products.

(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 products, pulverized products, squeezed juice, extracts, etc.) may also be used.

(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.

(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, extract, etc.) may also be used.

(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.

(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 among them, the content is high in kagome kelp and mozuku seaweed, and it is preferably used in the present invention. 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.

(Citrulline)
The citrulline of the present invention may be either L-citrulline or D-citrulline, but is preferably L-citrulline. Citrulline may be obtained by any method, such as by chemical synthesis or fermentation. Furthermore, citrulline may be in the form of a salt, and the salt is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include inorganic acid salts, organic acid salts, metal salts, and ammonium 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 fruit, and flaxseed together with chitosan.

These plant materials are preferably used as processed plant products such as dried plants, crushed plants, juices, and extracts. Crushed plants can be in the form of powders or 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, such as water (warm water or hot water), ethanol, or aqueous ethanol. Commercially available plant materials may also be used.

(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.

(Chia seeds)
Chia is an annual plant of the Lamiaceae family, Salvia genus, 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.

(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.

(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.

The composition of the present invention has the effect of suppressing an increase in blood cholesterol levels, and can be used, for example, as so-called health foods such as pharmaceuticals (including quasi-drugs), functional foods whose efficacy has been approved by designated organizations, such as foods for specified health uses, foods with nutrient functions, and foods with functional claims, as well as general foods, food additives, feed, etc.

The composition of the present invention can be used as a blood cholesterol-lowering composition for suppressing elevated blood cholesterol levels. 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 elevated blood cholesterol levels. For example, the scope of the present invention includes products that display on the product itself, packaging, instructions, or promotional materials that the product has the function of suppressing elevated blood cholesterol levels. Note that the blood cholesterol-lowering composition of the present invention is not limited to products that display on the product packaging, etc., the combined components of the present invention (chitosan and other specified materials) as the active ingredients for suppressing elevated blood cholesterol levels. For example, the active ingredient may not be specified, and products that display only chitosan as the active ingredient may also be used.

Specific 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."

The composition of the present invention may be in the form of, for example, a tablet, capsule, powder, granules, liquid, grain, rod, plate, block, solid, round, paste, cream, caplet, gel, chewable, or stick. Among these, tablet, capsule, powder, granule, and liquid forms are particularly preferred. Specific examples include supplements, packaged beverages filled in PET bottles, cans, jars, etc., instant beverages that are dissolved in water (hot water), milk, fruit juice, green juice, etc., and food additives. These are preferred because they are easy to consume during meals and can enhance palatability.

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 that achieves their desired effect.

Generally, when the composition of the present invention is a pharmaceutical or supplement, the components of the present invention are preferably contained in an amount of 0.1 to 100% by mass, more preferably 1 to 85% by mass, and even more preferably 5 to 70% by mass, of the total dry 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, more preferably 0.001 to 1% by mass, and even more preferably 0.01 to 0.5% by mass, of the total amount.

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

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 dry mass of the composition of the present invention, more preferably 90% or more, even more preferably 95% or more, and particularly preferably 100%.

There are no particular restrictions on the amount of intake of the composition of the present invention, but from the perspective of more significantly exhibiting the effects of the present invention, it is preferable to ingest the components of the present invention so that their daily intake 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 dose in a single container or divided into, for example, two or three containers so that the daily intake is the above-mentioned amount.

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 0.75:1 to 1000:1, even more preferably 1:1 to 500:1, and particularly preferably 1:1 to 300:1. By ensuring that the blending ratio of chitosan to other materials is within the above range, the effects of the present invention can be more effectively achieved.

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, vitamin P) and oil-soluble vitamins (vitamins A, D, E, 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.

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 substance was 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 while 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 while shaking at 100 rpm.

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

3 mL of the supernatant was removed, taking care not to aspirate the precipitate (test substance), and an equal volume of ethyl acetate was added. The mixture was vortexed for 30 seconds. After vortexing, the mixture was centrifuged at 2000 rpm for 10 minutes.

1.5 mL of the top layer of the liquid was transferred to a new Falcon and evaporated to dryness using a centrifugal evaporator.

600 μL of 2-propanol was added to the dried material and sonicated for 10 minutes.

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

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.

(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.

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. 25 μL of sample was also added to 62.5 μL of blank enzyme solution, and reacted in the same way to serve as a sample blank.

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

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%.

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

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

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

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.

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

Take the above tablets once or two or three times a day with water.

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

Chitosan 40%
Resveratrol 1%
Lycopene 1%
Soy isoflavones 1%
Noni leaves 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%

Take four of the above capsules once a day or two to four times a day with water.

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

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

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

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

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

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

The composition of the present invention has the effect of suppressing an increase in blood cholesterol, making it highly useful industrially.

Claims (1)

Chitosan and
An oral composition for suppressing an increase in blood cholesterol, characterized by containing soy isoflavone and chitosan as an active ingredient .