JP7321743B2 - solid composition - Google Patents

Description

The present invention relates to solid compositions containing chlorogenic acids and hesperidins.

Chlorogenic acids are representative polyphenols contained in coffee, and are reported to have physiological actions such as antioxidant action, hypotensive action, and higher brain function improving action (for example, Patent Document 1). So far, many foods and drinks containing chlorogenic acids have been put on the market.

On the other hand, hesperidins, which are flavonoids abundantly contained in citrus fruits, are reported to have physiological effects such as capillary strengthening action and blood flow improving action. In addition, it has been reported that when hesperidin glycosides or a mixture of hesperidin glycosides and hesperidin is added to food and drink such as vegetable drinks, grassy smell, bitterness, astringency, etc. can be reduced (Patent Document 2).

JP 2018-39797 A JP-A-11-318379

Solid compositions such as tablets and powders are excellent in portability and storage stability, and are suitable forms for easily enjoying the physiological effects of chlorogenic acids. However, it was found that chlorogenic acids in a solid state such as powder leave a strong sensation of irritation on the tongue after ingestion, and this irritation remaining on the tongue makes it difficult to ingest chlorogenic acids in the form of a solid composition. Here, the irritation that chlorogenic acids leave on the tongue is the irritation felt on the tongue about 10 seconds after ingestion. ).
Accordingly, the present invention relates to providing a solid composition containing chlorogenic acids that leaves little irritation on the tongue.

Means for Solving the Problems In view of the above problems, the present inventors conducted extensive studies and found that the irritating feeling of the chlorogenic acids that remains on the tongue can be suppressed by including hesperidins in a specific ratio with respect to the chlorogenic acids.

Thus, the present invention provides the following components (A) and (B):
Provided is a solid composition containing (A) chlorogenic acids and (B) hesperidins, wherein the content mass ratio of component (B) to component (A) [(B)/(A)] is 0.3 or more. It is.

According to the present invention, it is possible to provide a solid composition containing chlorogenic acids that leaves little irritation on the tongue.

The solid composition of the present invention contains (A) chlorogenic acids. Here, the term “chlorogenic acids” as used herein means monocaffeoylquinic acids such as 3-caffeoylquinic acid, 4-caffeoylquinic acid and 5-caffeoylquinic acid, 3-feruloylquinic acid, 4 -feruloyl quinic acid and 5-feruloyl quinic acid is a collective term for monoferuloyl quinic acid. In the present invention, at least one of the above six types may be contained.
Component (A) may be in the form of a salt or hydrate. The salt is not particularly limited as long as it is physiologically acceptable, and examples thereof include alkali metal salts.

As component (A), a commercially available reagent may be used, but a plant extract containing component (A) may also be used.
The plant is not particularly limited as long as it contains the component (A). One or two or more selected from Nanten leaves, burdock, eggplant skin, plum fruit, coltsfoot, and grape family plants. Among them, coffee beans are preferable from the viewpoint of the content of chlorogenic acids. The bean species and production area of the coffee beans are not particularly limited.

The coffee beans may be green coffee beans, roasted coffee beans, or both. From the viewpoint of the content of chlorogenic acids, the roasted coffee beans are preferably lightly roasted coffee beans. The range of the L value of the lightly roasted coffee beans is preferably 27 or more and less than 62, more preferably 29 or more and 60 or less, and still more preferably 35 or more and 55 or less. Here, the "L value" as used herein means that black is L value 0 and white is L value 100, and the lightness of roasted coffee beans is measured by a color difference meter (for example, spectrophotometer SE2000, Co., Ltd.) after pulverization. ) manufactured by Nippon Denshoku Co., Ltd.).
The extraction method and extraction conditions can be selected as appropriate. For example, water, hot water, or a water-soluble organic solvent can be used by known methods such as batch extraction, drip extraction, and column extraction. Examples of water-soluble organic solvents include lower alcohols such as ethanol. For the extraction method, for example, the methods described in JP-A-58-138347, JP-A-59-51763, JP-A-62-111671, and JP-A-5-236918 can be employed. can. The coffee beans subjected to extraction may be unground or ground.
After the extraction, the obtained extract may be concentrated by known means such as normal pressure concentration, vacuum concentration, membrane concentration, etc. Alternatively, the extract or concentrate may be purified. Drying can be performed by known means such as spray drying and freeze drying.
The form of the component (A) reagent and the plant extract containing the component (A) is solid (powder, granules, etc.) at room temperature (25°C).

In the solid composition of the present invention, the content of component (A) is preferably 2.0% by mass or more, more preferably 5.0% by mass or more, still more preferably 7.0% by mass or more, from the viewpoint of physiological activity. It is 0% by mass or more. In addition, from the viewpoint of suppressing irritation, the content is preferably 80% by mass or less, more preferably 70% by mass or less, still more preferably 60% by mass or less, even more preferably 30% by mass or less, and even more preferably 15% by mass or less. be.
In this specification, the content of component (A) is defined based on the total amount of the above six types. In addition, when the component (A) is a salt or hydrate, the content of the component (A) is a value converted into chlorogenic acids, which are free acids. The component (A) can be analyzed by, for example, an analytical method suitable for the condition of the sample to be measured among commonly known measuring methods. For example, it can be analyzed by the method described in Examples below.

The solid composition of the present invention contains (B) hesperidins. Hesperidins is a general term for hesperidin, sugar adducts in which sugar is bound to hesperidin, and methylated products of hesperidin.
Hesperidin is a glycoside in which rutinose (L-rhamnosyl-(α1→6)-D-glucose) is β-bonded to the hydroxyl group at the 7-position of hesperetin (5,7,3'-trihydroxy-4'-methoxyflavanone). and hesperidin sugar adducts are compounds in which another sugar such as glucose, maltose, fructose, rhamnose, or lactose is bound to the sugar moiety (rutinose moiety) of hesperidin. From the viewpoint of solubility, the sugar adduct of hesperidin is preferably glucosylhesperidin in which 1 to 10 glucoses are bound to hesperidin, and more preferably monoglucosylhesperidin in which 1 glucose is bound. The number of added glucose may have a distribution, and the average number of added moles of glucose per 1 mole of hesperidin is preferably 1-10.

The methylation position and the number of methylated products of hesperidin are not particularly limited. Methylhesperidin is known to mainly include chalcone-type compound (1) and flavanone-type compound (2), and examples thereof include those having the structures shown below.

(Wherein, R represents a hydrogen atom or a methyl group)

Here, methylhesperidin as a pharmaceutical additive and food additive is mainly treated as a mixture of compounds (3) and (4).

(Wherein, Gl is a glucose residue, Rh represents a rhamnose residue. In addition, Gl-2 is the 2nd position of the glucose residue (including the 3rd position in the case of (3-1)), Rh- 2 represents the 2nd position of the rhamnose residue.)
Incidentally, hesperidin methyl chalcone as a cosmetic raw material is handled as a compound represented by (5). A composition rich in chalcone-type compounds is also called hesperidin methyl chalcone.

(Wherein, R represents a hydrogen atom or a methyl group.)

In the present invention, methylhesperidin may contain both chalcone-type compound (1) and flavanone-type compound (2) shown above, or may contain only one of each.
In the present invention, a more preferred methylhesperidin is a mixture of compound (3) and compound (4).

Component (B) is preferably a sugar addition product of hesperidin, more preferably glucosylhesperidin, and even more preferably monoglucosylhesperidin, from the viewpoint of suppressing the irritation that chlorogenic acids leave on the tongue.

A hesperidin glycosylated product can be obtained, for example, by a method of reacting hesperidin with a glycosyltransferase in the presence of a glycosyl donor (see Japanese Patent No. 3060227, etc.). Alternatively, methylhesperidin can be obtained, for example, by dissolving hesperidin in an aqueous sodium hydroxide solution, reacting the alkaline solution with a corresponding amount of dimethyl sulfate, neutralizing the reaction mixture with sulfuric acid, extracting with n-butyl alcohol, and distilling off the solvent. After removal, it can be obtained by a method of recrystallization with isopropyl alcohol (see Sakiyoku, Nihon Kagaku Zasshi, 79, 733-6 (1958)).
A commercially available product may be used as component (B).

In the solid composition of the present invention, the content of component (B) is preferably 2.0% by mass or more, more preferably 5.0% by mass or more, still more preferably 7.0% by mass or more, from the viewpoint of effectiveness. It is 0% by mass or more. In addition, since hesperidins produce a characteristic bitterness as the concentration increases, the content is preferably 80% by mass or less, more preferably 70% by mass or less, and even more preferably 60% by mass, from the viewpoint of suppressing the bitterness of hesperidins. Below, more preferably 30% by mass or less, more preferably 15% by mass or less.
In the present specification, the content of component (B) is in terms of total hesperetin glycosides. Here, total hesperetin glycoside content (dry matter) (%) = hesperidin content (%) + monoglucosyl hesperidin content (%) + α-glucosyl residue amount (%) liberated by glucoamylase treatment. . Component (B) can be analyzed, for example, by the method described in Examples below.

In the solid composition of the present invention, the content mass ratio of component (B) to component (A) [(B)/(A)] is 0.3 or more. By setting it as such a mass ratio, the irritation|stimulation feeling which remains on the tongue of chlorogenic acids in a solid composition can be suppressed. The mass ratio [(B)/(A)] of the component (B) to the component (A) is preferably 0.32 or more, more preferably 0.32 or more, from the viewpoint of suppressing the irritation of the chlorogenic acids remaining on the tongue. It is 0.4 or more, more preferably 0.5 or more, and still more preferably 0.7 or more. From the viewpoint of suppressing the bitterness of hesperidins, the mass ratio of component (B) to component (A) [(B)/(A)] is preferably 8 or less, more preferably 3 or less, and still more preferably It is 2.5 or less, more preferably 2.0 or less, still more preferably 1.5 or less.

In addition to the above components, the solid composition of the present invention contains minerals (for example, calcium, magnesium, iron, zinc, chromium, selenium, manganese, molybdenum, copper, iodine, phosphorus, potassium, sodium), vitamins (e.g., vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, folic acid and their salts, or their esters), sweeteners ( For example, monosaccharides, oligosaccharides, sugar alcohols, synthetic sweeteners), acidulants, flavors, coloring agents, preservatives, and other additives may be added as appropriate. The content of the additive can be appropriately set within a range that does not impair the object of the present invention.

The solid composition of the present invention is not particularly limited as long as it is in a solid state at room temperature (25°C). Specific dosage forms include capsules, granules, powders, tablets, pills, and the like. mentioned. Among these, tablets and powders are preferable, and chewable tablets are more preferable, because they can be taken in small amounts at one time and are easy to take.

When preparing such a solid composition, an acceptable carrier can be used in combination as necessary. Examples of carriers include excipients (e.g., lactose, starches, crystalline cellulose, sucrose, mannitol, light anhydrous silicic acid, calcium hydrogen phosphate), binders (e.g., hydroxypropylmethylcellulose, hydroxypropylcellulose, gelatin, pregelatinized starch, polyvinylpyrrolidone, polyvinyl alcohol, pullulan, methylcellulose, hydrogenated oil), disintegrant (e.g. carmellose, carmellose calcium, croscarmellose sodium, crospovidone, corn starch, low-substituted hydroxypropylcellulose), lubricating agent. agents (e.g. calcium stearate, magnesium stearate, sucrose fatty acid esters, sodium stearyl fumarate, talc, silicon dioxide), flavoring agents (e.g. stevia, aspartame), fragrances, fillers, surfactants, dispersants, Buffering agents, coating agents, diluents and the like are included. The content of the carrier can be appropriately set within a range that does not impair the object of the present invention.

The solid composition of the present invention can be produced according to a conventional method, and any suitable method can be employed. For example, component (A) and component (B), and optionally a carrier and/or additive, are mixed so that the mass ratio of component (A) and component (B) is within the above range. can be done. The mixing order of each component is not particularly limited, and they may be added in any order or at the same time. As a mixing method, an appropriate method such as stirring or shaking can be adopted, and a mixing device may be used. The mixing method of the mixing device may be a container rotation type or a container fixed type. As the container rotating type, for example, a horizontal cylindrical type, a V type, a double cone type, a cubic type, etc. can be adopted. As the fixed container type, for example, a ribbon type, a screw type, a conical screw type, a paddle type, a fluidized bed type, a Phillips blender and the like can be adopted.
Moreover, it is good also as a granule by a well-known granulation method. Granulation methods include, for example, spray granulation, fluid bed granulation, compression granulation, tumbling granulation, stirring granulation, extrusion granulation, and powder coating granulation. Granulation conditions can be appropriately selected depending on the granulation method.

In the case of tablets, a mixture of components (A) and (B) and, if necessary, carriers and/or additives may be directly compressed and molded as a raw material powder, or granulated by the above granulation method. After that, the granules may be compressed and molded using a tableting machine.
When the tablets are produced directly or by compressing the granules and molding them, a commonly used tableting machine such as a rotary tableting machine or a single-shot tableting machine can be used as the tableting machine.
The compression molding pressure during tableting is preferably about 10 to 30 MPa from the viewpoint of maintaining the hardness of the molding.
Further, the tablet hardness is preferably a hardness that can withstand transportation, storage, etc., and is preferably about 10N to 200N.
The shape of the tablet may be round, oval, elliptical, square, or other irregular shape, but the round shape is preferable from the viewpoint of ease of administration. In the case of round tablets, the diameter is preferably 3 to 30 mm, more preferably 3 to 20 mm, from the viewpoint of ease of administration. Moreover, it is preferable that the weight of the tablet is 0.1 to 6 g per preparation from the viewpoint of convenience and effectiveness.

[Analysis of chlorogenic acids]
Chlorogenic acid was quantified by a gradient method at a column temperature of 35° C. using a high-performance liquid chromatograph manufactured by Shimadzu Corporation, equipped with Cadenza CD-C18 manufactured by Intact Co., Ltd. (inner diameter 4.6 mm×length 150 mm, particle size 5 μm).

(Analysis conditions)
・Sample injection volume: 10 μL
・Flow rate: 1.0 mL/min
・Ultraviolet absorption photometer detection wavelength: 325 nm
・Column oven set temperature: 35°C
Eluent A: 5% acetonitrile containing 0.05 mol/L acetic acid, 0.01 mol/L sodium acetate, and 0.1 mmol/L HEDP (1-hydroxyethane-1,1-diphosphonic acid) Eluent B : Acetonitrile

(Concentration gradient condition)
Time (min) Eluent A (% by volume) Eluent B (% by volume)
0.0 100% 0%
10.0 100% 0%
15.0 95% 5%
20.0 95% 5%
22.0 92% 8%
50.0 92% 8%
52.0 10% 90%
60.0 10% 90%
60.1 100% 0%
70.0 100% 0%

When the retention time of chlorogenic acids was confirmed using standard products, the results were as follows.
・3-caffeoylquinic acid 5.3 minutes ・5-caffeoylquinic acid 8.8 minutes ・4-caffeoylquinic acid 11.6 minutes ・3-feruloylquinic acid 13.0 minutes ・5-feruloylquinic acid Acid 19.9 minutes 4-feruloylquinic acid 21.0 minutes Chlorogenic acids were quantified from the area value of the peak that coincided with the above retention time.

[Analysis of hesperidins]
Hesperidin was quantified by a gradient method at a column temperature of 35° C. using a high-performance liquid chromatograph manufactured by Shimadzu Corporation equipped with Cadenza CD-C18 manufactured by Intact Co., Ltd. (inner diameter 4.6 mm×length 150 mm, particle size 5 μm).

(Analysis conditions)
・Sample injection volume: 10 μL
・Flow rate: 1.0 mL/min
・Ultraviolet absorption photometer detection wavelength: 280 nm
・Column oven set temperature: 35°C
Eluent A: 5% acetonitrile containing 0.05 mol/L acetic acid, 0.01 mol/L sodium acetate, and 0.1 mmol/L HEDP (1-hydroxyethane-1,1-diphosphonic acid) Eluent B : Acetonitrile

(Concentration gradient condition)
Time (min) Eluent A (% by volume) Eluent B (% by volume)
0.0 100% 0%
10.0 100% 0%
15.0 95% 5%
20.0 95% 5%
22.0 92% 8%
45.0 92% 8%
47.0 87.5% 12.5%
60.0 87.5% 12.5%
62.0 10.0% 90.0%
70.0 10.0% 90.0%
70.1 100% 0%
80.0 100% 0%

Examples 1-7 and Comparative Examples 1-4
Each raw material component was uniformly mixed according to the formulation shown in Table 1 to obtain a powdered food.
The following sensory evaluation was performed on the obtained powdered food. Table 1 shows the results.

[Irritation that remains on the tongue derived from chlorogenic acids]
After ingestion of 200 mg of the powdered food obtained in each of the above Examples and Comparative Examples, the sensation of irritation remaining on the tongue was evaluated. Evaluation criteria were as follows, evaluation was performed by three expert panels, and scores were determined through discussion. The irritation remaining on the tongue of the powdered food of Example 1 was scored as "1", and the sensation of irritation remaining on the tongue of the powdered food of Comparative Example 4 was scored as "5".
[Stimulation that remains on the tongue]
1: Weak sense of irritation remaining on the tongue after ingestion 2: Slightly weak sense of irritation remaining on the tongue after ingestion 3: Slightly strong sense of irritation remaining on the tongue after ingestion 4: Strong sense of irritation remaining on the tongue after ingestion 5: After ingestion, the feeling of irritation that remains on the tongue is very strong.

[Bitter taste of hesperidins]
The bitterness was evaluated when 200 mg of the powdered food obtained in each of the above Examples and Comparative Examples was ingested. Evaluation criteria were as follows, evaluation was performed by three expert panels, and scores were determined through discussion. The bitterness of the powdered food of Comparative Example 4 was scored as "1", and the bitterness of the powdered food of Example 1 was scored as "5".
〔bitter taste〕
1: weak bitterness 2: slightly weak bitterness 3: slightly strong bitterness 4: strong bitterness 5: very strong bitterness

Examples 8-13 and Comparative Example 5
Each component was uniformly mixed with the formulation shown in Table 2, and powdered food was obtained in the same manner as in Example 1.
Sensory evaluation was performed in the same manner as in Example 1, except that the obtained powdered food was evaluated on a 5-point scale with the irritation remaining on the tongue of the powdered food of Comparative Example 5 as a score of "5" and the bitterness as a score of "1". did Table 2 shows the results.

Production Example 1 Production of Chlorogenic Acids Preparation Ground coffee beans were extracted with hot water, dissolved in an aqueous ethanol solution, filtered, and the resulting filtrate was treated with activated carbon to obtain a green coffee bean extract. A powdery chlorogenic acid formulation was obtained by spray drying.
Chlorogenic acids in chlorogenic acid preparations (3-caffeoylquinic acid, 4-caffeoylquinic acid, 5-caffeoylquinic acid, 3-feruloylquinic acid, 4-feruloylquinic acid, 5-feruloylquinic acid) was 30% by mass.

Examples 14-15 and Comparative Example 6
Each component was uniformly mixed with the composition shown in Table 3, and powdered food was obtained in the same manner as in Example 1.
The obtained powdered food was subjected to sensory evaluation (stimulation left on the tongue derived from chlorogenic acids) in the same manner as in Example 1. Table 3 shows the results.

From Tables 1 to 3, it was confirmed that the irritating feeling of the chlorogenic acids remaining on the tongue can be suppressed by containing the hesperidins in a specific amount ratio with respect to the chlorogenic acids.

Claims (8)

The following components (A) and (B):
(A) 2.0% by mass or more of chlorogenic acids
(B) contains hesperidins, the content mass ratio of component (B) to component (A) [(B)/(A)] is 0.3 or more and 8 or less , and solid chlorogenic acids are applied to the tongue A solid composition that is ingested in contact form . 2. The solid composition according to claim 1 , wherein the content of component (A) is 80% by mass or less. 3. The solid composition according to claim 1, wherein the content of component (B) is 2.0% by mass or more. 4. The solid composition according to any one of claims 1 to 3 , wherein the content of component (B) is 80% by mass or less. The solid composition according to any one of claims 1 to 4 , wherein component (B) is glucosyl hesperidin. The solid composition according to any one of claims 1 to 5, which is granules, powders, tablets or pills. The solid composition according to any one of claims 1 to 5, which is a tablet or powder. The following components (A) and (B):
(A) chlorogenic acids 2.0% by mass or more
(B) Hesperidins
wherein the content mass ratio of component (B) to component (A) [(B)/(A)] is 0.3 or more and 8 or less, and is a chewable tablet.