JP6986345B2 - Oral composition and its production method - Google Patents

Description

The present invention relates to an oral composition.

Various components having various physiological activities have been found so far, and their application to foods and drinks including health foods is being attempted. Among such physiologically active ingredients, polyphenols, which are abundant in red wine and tea and have strong antioxidant activity, are expected to have effects such as anti-arteriosclerosis, anti-allergy, and blood flow enhancement. Recognized as an important ingredient in.

As one of the attempts to apply polyphenols to foods and drinks, a technique for dissolving poorly soluble polyphenols in water has been developed. For example, Patent Document 1 discloses a technique for adding a sugar to a sparingly soluble polyphenol having a rhamnose acid structure using an enzyme.

However, in order to efficiently prepare a composition containing polyphenols and exert the desired effect, it is required to study from various points such as compounding and manufacturing process and to improve the solubility.

Japanese Unexamined Patent Publication No. 2013-215155

The present invention is an oral composition containing a poorly soluble polyphenol, and an object of the present invention is to provide an oral composition having high recoverability in a manufacturing process, efficiently and of uniform quality.

The present inventors have a novel problem that when a sparingly soluble polyphenol contains a 1-vinyl-2-pyrrolidone polymer or cyclodextrin, the components remain in the container in the manufacturing process and the recoverability is impaired. I found it.

Therefore, as a result of studies to solve the above problems, the present inventors have found that the recoverability in the manufacturing process can be improved by containing the sparingly soluble polyphenol, the 1-vinyl-2-pyrrolidone polymer and the cyclodextrin together. We have found and completed the present invention.

That is, the present invention provides the oral compositions listed below.
Item 1. An oral composition containing (A) a poorly soluble polyphenol, (B) a 1-vinyl-2-pyrrolidone polymer, and (C) a cyclodextrin.
Item 2. Item 2. The oral composition according to Item 1, further comprising (D) at least one selected from the group consisting of stearate and terpenoids.
Item 3. Item 2. The oral composition according to Item 1 or Item 2, wherein the component (A) is a flavonoid-based polyphenol.
Item 4. Item 2. The oral composition according to any one of Items 1 to 3, wherein the total content of the component (A) is 0.00001w / v% to 90w / v%.
Item 5. Item 2. Oral according to any one of Items 1 to 4, wherein the total content of the component (B) is 0.000000001 to 100,000 parts by weight with respect to 1 part by weight of the total content of the component (A). Composition.
Item 6. Item 2. Oral according to any one of Items 1 to 5, wherein the total content of the component (C) is 0.0000001 to 10000 parts by weight with respect to 1 part by weight of the total content of the component (A). Composition.
Item 7. Item 6. The oral composition according to any one of Items 1 to 6, which is in the form of powder, tablet, granule, capsule, drink or jelly.
In another embodiment, the component (B) is at least one selected from the group consisting of polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K50, polyvinylpyrrolidone K60, polyvinylpyrrolidone K85 and polyvinylpyrrolidone K90. It may be the oral composition according to Item 1.
In another embodiment, the oral composition according to Item 1, wherein the component (C) is at least one selected from the group consisting of α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin. ..
In another form, it may be the oral composition according to Item 1, which is a food or drink, a health food, a food additive, a pharmaceutical product, a quasi drug or a feed.

The present invention also provides the oral compositions listed below.
Item 8. An oral composition containing polymethoxyflavonoids and (B) 1-vinyl-2-pyrrolidone polymer.
Further, in another form, the polymethoxyflavonoids may be the oral composition according to Item 8, wherein the polymethoxyflavonoids are nobiletin.
In another embodiment, it may be the oral composition according to Item 8, wherein the total content of the polymethoxyflavonoids is 0.00001w / v% to 90w / v%.
Item 8. The oral composition according to Item 8, wherein in another embodiment, the total content of the component (B) is 0.0000001 to 100,000 parts by weight with respect to 1 part by weight of the total content of the polymethoxyflavonoids. Can be.
In another form, it may be the oral composition according to Item 8, which is in the form of a powder, a tablet, a granule, a capsule, a drink or a jelly.
In another embodiment, item (B) is at least one selected from the group consisting of polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K50, polyvinylpyrrolidone K60, polyvinylpyrrolidone K85 and polyvinylpyrrolidone K90. Can be the oral composition described in.
In another form, it may be the oral composition according to Item 8, which is a food or drink, a health food, a food additive, a pharmaceutical product, a quasi drug or a feed.

The oral composition of the present invention contains (A) a sparingly soluble polyphenol, (B) a 1-vinyl-2-pyrrolidone polymer, and (C) a cyclodextrin to improve recoverability in the manufacturing process. Can be done. Further, in the oral composition of the present invention, by coexisting the above-mentioned component (A), component (B), and component (C), the dispersibility in water is improved, and the drug is rapidly dissolved and released. Is also excellent. Further, the oral composition of the present invention has improved solubility and excellent bioabsorbability of the drug by coexisting the above-mentioned component (A), component (B), and component (C).

It is a graph which shows the result of having measured the dissolved amount of curcumin by high performance liquid chromatography in the evaluation of solubility. It is a graph which shows the result of having measured the elution amount of curcumin by high performance liquid chromatography in the evaluation of the elution property.

[Oral composition]
The oral composition of the present invention is
(A) Poorly soluble polyphenols,
It contains (B) 1-vinyl-2-pyrrolidone polymer and (C) cyclodextrin.

[(A) component]
As used herein, polyphenol means a general term for components having a plurality of phenolic hydroxy groups in the same molecule. Further, in the present specification, the poorly soluble polyphenol means a component of polyphenols that is difficult to dissolve in water. The solubility of the poorly soluble polyphenol in water is not particularly limited, but for example, the solubility in pure water at 25 ° C. can be 1 g / L or less, preferably 0.5 g / L or less, preferably 0.4 g / L. It is more preferably L or less, further preferably 0.3 g / L or less, further preferably 0.2 g / L or less, particularly preferably 0.1 g / L or less, and 0. Most preferably, it is 0.05 g / L or less.

The poorly soluble polyphenols are structurally roughly classified into flavonoid-based polyphenols and phenolic acid-based polyphenols. Among these, flavonoid-based polyphenols are a group of compounds having a 2-phenylchromone skeleton, and are further classified into flavonoids, xanthonoids, stylpenoids, chalcones, lignoids, curcuminoids and the like. These flavonoid-based polyphenols have different carbon numbers that connect two benzene rings due to their structure, and such a difference can contribute to the influence on the reactivity and physiological activity of polyphenols.

The components typified by the flavonoids include, for example, isoflavones such as daizein, daidin and genistin; anthocyanins such as cyanidin, cyanine, delphinin, delphinidin, malvidin, peragonidin, peonidin and petunidin; polymethoxy such as nobiletin and tangeretin. Flavonoids; flavanones such as hesperidin, hesperetin, naringin, naringenin, citronin, liquirtin; flavanols such as catechin, epicatechin, epigalocatechin, epicatechin gallate, epigalocatecingalate, theaflavin; kercetin, rutin, kenferol, mylicetin, Examples include flavonols such as catechin.

Of these flavonoids, isoflavones have two carbon atoms connecting the two benzene rings. Anthocyanins, polymethoxyflavonoids, flavanones, flavanols and flavonols have three carbon atoms connecting two benzene rings.

Examples of the components typified by the above-mentioned xanthonoids include mandiferrin, piceatannol and the like. In xanthonoids, the number of carbon atoms connecting two benzene rings is one.

Examples of the component typified by the above-mentioned stylpenoid include resveratrol and the like. In sterpenoids, the number of carbon atoms connecting two benzene rings is two.

Examples of the component typified by the above chalcone include carthamin and the like. In chalcone, the number of carbon atoms connecting two benzene rings is three.

Examples of the components typified by the above-mentioned lignoid include lignan, sesamin, sesamolin, sesaminol, sesamol and the like. In lignoids, the number of carbon atoms connecting two benzene rings is four.

Examples of the components typified by the above curcuminoids include curcumin, dimethoxycurcumin, bisdimethoxycurcumin and the like. Curcuminoids have seven carbon atoms connecting two benzene rings.

Examples of the phenolic acid-based polyphenol include ellagic acid, chlorogenic acid, cocoa mass polyphenol, coumarin, and rosmarinic acid.

Among these (A) sparingly soluble polyphenols, flavonoid-based polyphenols are preferable from the viewpoint of remarkably exerting the effects of the present invention, and at least one selected from the group consisting of flavonoids, xanthonoids, stylpenoids, chalcones, lignoids and curcuminoids is selected. More preferably, at least one selected from the group consisting of polymethoxyflavonoids, flavanones, flavanols, flavonols, stilpenoids, lignoids and chalconeoids is even more preferred, and more preferably selected from the group consisting of flavanones, flavonols, flavonols, stilpenoids, lignoids and chalconeoids. At least one of them is even more preferable. From another point of view, (A) the sparingly soluble polyphenol is preferably at least one selected from the group consisting of nobiletin, hesperidin, catechin, rutin, resveratrol, sesamine and curcumin, preferably nobiletin, hesperidin and resveratrol. And at least one selected from the group consisting of curcumin, more preferably at least one selected from the group consisting of hesperidin, resveratrol and curcumin.

(A) The poorly soluble polyphenol may be of natural origin, chemically synthesized, or a commercially available product may be used. Further, when it is a naturally-derived poorly soluble polyphenol, it may be contained in various plant extracts, purified plants, or crushed plants. The plant parts used include, but are not limited to, pericarp, fruits, juices, leaves, stems, seeds and the like. In addition, these extracts, refined products or pulverized products are prepared according to a conventional method, and may undergo steps such as cutting, crushing, squeezing, pulverizing, drying, concentrating, filtering, sieving, homogenizing, and sterilizing. For example, as nobiletin, those contained in Shikuwasa, mandarin oranges, ponkan and the like can be used as naturally-derived poorly soluble polyphenols. Further, for example, hesperidin can be used as a naturally-derived poorly soluble polyphenol contained in mandarin oranges, mandarin oranges and the like. Further, for example, as catechin, those contained in green tea, black tea, oolong tea and the like can be used as naturally derived sparingly soluble polyphenols. Further, for example, rutin can be used as a naturally-derived poorly soluble polyphenol contained in Sophorae Fructus, buckwheat, adzuki bean and the like. Further, for example, resveratrol can be used as a naturally-derived sparingly soluble polyphenol contained in grapes, Japanese knotweed, etc. and red wine. Further, for example, curcumin can be used as a naturally-derived poorly soluble polyphenol contained in turmeric or the like.

(A) The poorly soluble polyphenol can be used alone or in combination of at least two or more.

In the oral composition of the present invention, the total content of the component (A) with respect to the total amount of the oral composition is appropriately set according to the type of the component (A), the content of other components, the dosage form and the like. The total content of the component (A) with respect to the total amount of the oral composition is not limited, but is, for example, 0.00001w / v% or more, more preferably 0.0001w / v% or more, still more preferably 0.0005w. / V% or more, particularly preferably 0.001 w / v% or more, and most preferably 0.005 w / v% or more. The total content of the component (A) with respect to the total amount of the oral composition is not limited, but is preferably 90 w / v% or less, more preferably 80 w / v% or less, still more preferably 70 w / v% or less, particularly. It is preferably 60 w / v% or less, and most preferably 50 w / v% or less. The total content of component (A) relative to the total amount of the oral composition is not limited, but is preferably 0.00001w / v% to 90w / v%, more preferably 0.0001w / v% to 80w / v%. It is more preferably 0.0005 w / v% to 70 w / v%, particularly preferably 0.001 w / v% to 60 w / v%, and most preferably 0.005 w / v% to 50 w / v%.

In the oral composition of the present invention, the daily dose of the component (A) for adults is appropriately set according to the type of the component (A), the content of other components, the dosage form, etc., and is not limited, but for example. , 0.00001 to 10000 mg, preferably 0.0001 to 7000 mg, more preferably 0.001 to 5000 mg, still more preferably 0.01 mg to 3000 mg, and particularly preferably 0.1 mg to 1000 mg.

When the component (A) is nobiletin, the daily dose of nobiletin for adults is not limited, but can be, for example, 0.00001 to 10000 mg, preferably 0.0001 to 5000 mg, and more preferably 0.001. It is ~ 500 mg, more preferably 0.01-500 mg, and particularly preferably 0.1-500 mg.

When the component (A) is hesperidin, the daily dose of hesperidin for adults is not limited, but can be, for example, 0.00001 to 10000 mg, preferably 0.0001 to 7000 mg, and more preferably 0.001. It is ~ 5000 mg, more preferably 0.01-3000 mg, and particularly preferably 0.1-1000 mg.

When the component (A) is resveratrol, the daily dose of resveratrol for adults is not limited, but can be, for example, 0.00001 to 10000 mg, preferably 0.0001 to 7000 mg, more preferably 0.0001 to 7000 mg. Is 0.001 to 5000 mg, more preferably 0.01 to 3000 mg, and particularly preferably 0.1 to 1000 mg.

When the component (A) is curcumin, the daily dose of curcumin for an adult is not limited, but can be, for example, 0.00001 to 10000 mg, preferably 0.0001 to 7000 mg, and more preferably 0.001. It is ~ 5000 mg, more preferably 0.01-3000 mg, and particularly preferably 0.1-1000 mg.

[(B) component]
Examples of the 1-vinyl-2-pyrrolidone polymer include a linear polymer of 1-vinyl-2-pyrrolidone and a crosslinked polymer of 1-vinyl-2-pyrrolidone. Specific examples of the 1-vinyl-2-pyrrolidone polymer include polyvinylpyrrolidone K17, polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, polyvinylpyrrolidone K50, polyvinylpyrrolidone K60, polyvinylpyrrolidone K85, polyvinylpyrrolidone K90, polyvinylpyrrolidone K120, and cloth. Povidon and the like can be mentioned.

(B) The 1-vinyl-2-pyrrolidone polymer has a new problem that when it coexists with the component (A), the component may remain in the container in the manufacturing process and the recoverability may be impaired. It was issued. Examples of the component (B) that cause such a problem include 1-vinyl-2-pyrrolidone polymers having a weight average molecular weight of about 4000 to 1,500,000, and polyvinylpyrrolidone K25, polyvinylpyrrolidone K30, and polyvinylpyrrolidone K50. , At least one selected from the group consisting of polyvinylpyrrolidone K60, polyvinylpyrrolidone K85 and polyvinylpyrrolidone K90. When the problem of recoverability arises due to the component (B), surprisingly, it is possible to improve the recoverability by coexisting with the component (A) and the component (C) described later.

(B) The 1-vinyl-2-pyrrolidone polymer may be chemically synthesized, or a commercially available product may be used. (B) The 1-vinyl-2-pyrrolidone polymer can be used alone or in combination of at least two or more.

In the oral composition of the present invention, the total content of the component (B) with respect to the total amount of the oral composition is appropriately set according to the content of other components, the dosage form and the like. The total content of the component (B) with respect to the total amount of the oral composition is not limited, but is, for example, 0.00001 w / v% or more, more preferably 0.0001 w / v% or more, still more preferably 0.0005 w. / V% or more, particularly preferably 0.001 w / v% or more, and most preferably 0.005 w / v% or more. The total content of the component (B) with respect to the total amount of the oral composition is not limited, but is preferably 5 w / v% or less, more preferably 1 w / v% or less, still more preferably 0.5 w / v% or less. Particularly preferably, it is 0.1 w / v% or less, and most preferably 0.05 w / v% or less. The total content of component (B) relative to the total amount of the oral composition is not limited, but is preferably 0.00001w / v% to 5w / v%, more preferably 0.0001w / v% to 1w / v%. More preferably 0.0005 w / v% to 0.5 w / v%, particularly preferably 0.001 w / v% to 0.1 w / v%, and most preferably 0.005 w / v% to 0.05 w / v%. Is.

In the oral composition of the present invention, the daily dose of the component (B) for adults is appropriately set according to the content of other components, the dosage form, etc., and is not limited, but is, for example, 0.00001 to 1000 mg. It is preferably 0.0001 to 5000 mg, more preferably 0.001 to 2000 mg, still more preferably 0.01 to 1000 mg, and particularly preferably 0.1 to 500 mg.

Further, in the oral composition of the present invention, the ratio of the content of the component (B) to the component (A) is not particularly limited, but as an example, the total content of the component (A) is 1 part by weight. On the other hand, the total content of the component (B) is usually 0.0000001 to 100,000 parts by weight, preferably 0.000001 to 10000 parts by weight, and preferably 0.0001 to 10000 parts by weight. It is more preferably 0.0001 to 1000 parts by weight, and particularly preferably 0.001 to 1000 parts by weight.

[(C) component]
(C) The cyclodextrin is not limited, and examples thereof include α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin, and any of them can be used. (C) The cyclodextrin can be, for example, at least one selected from the group consisting of α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin, preferably α-cyclodextrin and / or β-. Cyclodextrin. It may have a higher-order annular structure. It is also possible to use a cyclodextrin derivative in which some or all of the hydroxyl groups present on the cyclodextrin are chemically modified. Chemically modified cyclodextrin derivatives include, for example, methylated cyclodextrin, ethylened cyclodextrin, acetylated cyclodextrin, hydroxypropylated cyclodextrin, hydroxyalkylated cyclodextrin, polymerized cyclodextrin, alkylsphon oxide cyclodextrin, and the like. Examples thereof include monochlorotriazinolated cyclodextrin and sulfobutylated cyclodextrin.

When a chemically modified cyclodextrin derivative is used, for example, dimethyl-α-cyclodextrin, hydroxypropyl-β-cyclodextrin, poly-β-cyclodextrin, 6-O-α-D-glucosyl- Β-Cyclodextrin, 6-O-α-maltosyl-β-cyclodextrin, methyl-β-cyclodextrin, and glucuronyl glucosyl-β-cyclodextrin, sulfobutyl ether-γ-cyclodextrin, preferably hydroxypropyl. Examples thereof include -β-cyclodextrin.

(C) Cyclodextrin may be chemically synthesized, or a commercially available product may be used. (C) Cyclodextrin can be used alone or in combination of at least two or more.

It has been found that (C) cyclodextrin may impair recoverability by coexisting with the component (A), such as the component remaining in the container in the manufacturing process. When the problem of recoverability arises due to the component (C), surprisingly, it is possible to improve the recoverability by coexisting with the component (A) and the component (B).

In the oral composition of the present invention, the total content of the component (C) with respect to the total amount of the oral composition is appropriately set according to the content of other components, the dosage form and the like. The total content of the component (C) with respect to the total amount of the oral composition is not limited, but is, for example, 0.00001 w / v% or more, more preferably 0.0001 w / v% or more, still more preferably 0.0005 w. / V% or more, particularly preferably 0.001 w / v% or more, and most preferably 0.005 w / v% or more. The total content of the component (C) with respect to the total amount of the oral composition is not limited, but is preferably 90 w / v% or less, more preferably 80 w / v% or less, still more preferably 70 w / v% or less, particularly. It is preferably 60 w / v% or less, and most preferably 50 w / v% or less. The total content of component (C) relative to the total amount of the oral composition is not limited, but is preferably 0.00001w / v% to 90w / v%, more preferably 0.0001w / v% to 80w / v%. It is more preferably 0.0005 w / v% to 70 w / v%, particularly preferably 0.001 w / v% to 60 w / v%, and most preferably 0.005 w / v% to 50 w / v%.

In the oral composition of the present invention, the daily dose of the component (C) for adults is appropriately set according to the content of other components, the dosage form, etc., and is not limited, but is, for example, 0.00001 to 10000 mg. It is preferably 0.0001 to 5000 mg, more preferably 0.001 to 5000 mg, still more preferably 0.01 to 5000 mg, and particularly preferably 0.1 to 5000 mg.

Further, in the oral composition of the present invention, the ratio of the content of the component (C) to the component (A) is not particularly limited, but as an example, the total content of the component (A) is 1 part by weight. On the other hand, the total content of the component (C) is usually 0.0000001 to 10000 parts by weight, preferably 0.000001 to 10000 parts by weight, and preferably 0.0001 to 10000 parts by weight. It is more preferably 0.0001 to 1000 parts by weight, and particularly preferably 0.001 to 1000 parts by weight.
[(D) component]
In the present invention, the oral composition may further contain at least one selected from the group consisting of (D) stearate and terpenoids, as long as the effects of the present invention are sufficiently exhibited.

The stearate is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Specific examples of the stearate include at least one selected from the group consisting of magnesium stearate, calcium stearate and sodium stearyl fumarate. Among these stearate, magnesium stearate is preferable from the viewpoint of not hindering the recoverability improving effect of the oral composition of the present invention.

The terpenoid is not particularly limited as long as it is pharmaceutically, pharmacologically (pharmaceutically) or physiologically acceptable. Terpenoids are specifically menthol, menthol, camphor, borneol, geraniol, cineole, citronellol, carboxylic, anator, eugenol, limonene, linalool, linalool acetate, timole, simene, terpineol, pinene, camphen, isobornole, fenchen. , Nerol, myrcene, milsenol, linalool acetate, lavandulol, and at least one selected from the group consisting of derivatives thereof. Here, examples of the "derivative" in the terpenoid include esterified derivatives, etherified derivatives, amidated derivatives, sulfonated derivatives, nitrated derivatives, nitrosated derivatives, halogenated derivatives and the like. Not limited. It is preferably an esterified derivative and / or an etherified derivative, and more preferably an esterified derivative. Examples of esterified derivatives include derivatives esterified with organic acids such as valerate, butyric acid, acetic acid, propionic acid and / or furancarboxylic acid. Further, these compounds may be d-form, l-form or dl-form.

As the terpenoid, an essential oil containing the above compound may be used. Examples of such essential oils include eucalyptus oil, bergamot oil, peppermint oil, cool mint oil, spare mint oil, peppermint oil, sardine oil, keihi oil, rose oil, cypress oil, butterfly oil, ylang ylang oil, orange oil, and the like. Examples thereof include chamomile oil, perilla oil, citronella oil, ginger oil, geranium oil, televisionn oil, peppermint oil, neroli oil, palmarosa oil, lavender oil, linaroe oil, lemon oil, rosemary oil, and Roman chamomile oil. These terpenoids may be used alone or in any combination of two or more.

Among these terpenoids, cyclic monoterpenes are preferable from the viewpoint of remarkably exerting the effect of the present invention, and at least one selected from the group consisting of menthol, menthone, camphor, borneol, citronellal, terpineol, limonene and geraniol is preferable. More preferred. Further, as the terpenoid, a monocyclic monoterpene is more preferable from the viewpoint of remarkably exerting the effect of the present invention, and at least one selected from the group consisting of menthol, menthone, terpineol and limonene is further preferable. Examples of the essential oil containing these include cool mint oil, peppermint oil, peppermint oil, cypress oil, rose oil and the like. From another point of view, menthol, camphor and borneol are more preferred, menthol and camphor are even more preferred, and even more preferably l-menthol, dl-menthol, d-camphor, and dl-camphor. At least one selected from the group is mentioned, particularly preferably l-menthol and / or d-camphor, and most preferably l-menthol. Examples of essential oils containing these include cool mint oil, peppermint oil, peppermint oil, camphor oil and the like.

The total content of at least one selected from the group consisting of stearate and terpenoids is not limited, but is preferably 0.00001w / v% to 50w / v%, more preferably 0.0001w / v%. It is ~ 50w / v%, more preferably 0.001w / v% -40w / v%, and even more preferably 0.01w / v% -25w / v%.

In the oral composition of the present invention, the daily dose of the component (D) for adults is appropriately set according to the content of other components, the dosage form, etc., and is not limited, but is, for example, 0.00001 to 10000 mg. It can be preferably 0.0001 to 5000 mg, more preferably 0.001 to 5000 mg, still more preferably 0.01 to 5000 mg, particularly preferably 0.1 to 5000 mg, and most preferably 0.1 to 500 mg. be.

The pH of the oral composition of the present invention may be appropriately changed depending on the embodiment and is not limited, but may be, for example, pH 3.5 to 7.5, preferably 3.8 to 7.2, and 4.0. ~ 7.0 is more preferable, and 4.5 to 6.5 is even more preferable.

[Use]
(A) Poorly soluble polyphenols are known to have antioxidant power and are expected to have effects such as anti-arteriosclerosis, anti-allergy, and blood flow enhancement. Therefore, foods and drinks, health foods, food additives, and quasi-drugs are expected. , It is recognized as an important ingredient in quasi-drugs, foods, etc. As used herein, the term "antioxidant" refers to an action of preventing oxidation of a living body by active oxygen or the like. Generally, when sparingly soluble polyphenols are used in liquids such as drinks, they are mainly used as dispersions, but if the dispersibility is poor, phenomena such as precipitation in containers may occur, and the desired total amount may be ingested. Can not. Further, even when taken in the form of tablets or powders, if the dispersibility is poor, a uniform solid substance cannot be produced. In addition, if the solubility is poor, the bioabsorbability also deteriorates, and it is possible that the original effect of the poorly soluble polyphenol cannot be exhibited. In the present invention, when the component (A) and the component (B) or the component (A) and the component (C) coexist, the component remains in the container in the manufacturing process, and the recoverability is impaired. By coexisting the components A), (B) and (C) in the oral composition, it is expected that the recoverability will be improved and the original antioxidant power of the poorly soluble polyphenol will be exhibited. .. Further, in the present invention, the solubility is improved by coexisting the component (A), the component (B) and the component (C) in the oral composition, so that the oral composition is excellent in bioabsorbability (high absorbency). It becomes possible to provide the composition.

After being prepared as a composition, the oral composition of the present invention can be processed into various foods and drinks such as solid, liquid and jelly, health foods, food additives, pharmaceuticals, quasi-drugs, feeds and the like. The oral composition of the present invention can be recovered in a known manufacturing process such as a mixing step with other components, a drying step of a composition, a compression step, a concentration step, a granulation step, a tablet making step, a filling step, and a dropping step. It can have the effect of sex and dispersibility. In the present specification, the recoverability means that the composition does not easily adhere to the manufacturing apparatus or the like or scatter in the atmosphere in the manufacturing process. Although not limited, it can be evaluated by, for example, the recovery rate of the composition before and after the composition is provided in one step of production. Further, in the present specification, the dispersibility means a property that each component in the composition can be stably dispersed in an aqueous medium.

[Food and drink]
The oral composition of the present invention can be blended as one component of food and drink. These foods and drinks are not limited, but can be foods and drinks that are used with the expectation of antioxidant effects such as anti-arteriosclerosis, anti-allergy, and blood flow enhancement. For example, medical treatment in hospitals and the like. Can be provided for patients at the institution. Alternatively, these foods and drinks can be provided as functional beverages or functional foods, but are not limited, and these functional foods and drinks can be provided in medical institutions, drug stores, convenience stores, and supermarkets. , Department stores, mail order, etc. Functional foods and drinks are foods and drinks with medicinal properties permitted and designated by the national government and public organizations, or functionality based on the content that the company has notified or approved the prescribed effect to the national government. Refers to the displayed food and drink. Examples of functional foods include foods for specified health use, foods with nutritional function, foods with functional claims, foods for the elderly, health supplements (balanced nutritional foods, supplements) and the like. It also includes foods and drinks including packages and containers, package inserts, instruction manuals, etc. that indicate pharmaceutical efficacy or functionality. Foods and drinks that indicate pharmaceutical efficacy or functionality in the application form to the national government are also included.

In the case of labeling for the purpose of antioxidative effect, there is no limitation, but for example, those who feel daily tiredness, those who feel poor sleep, those who feel light sleep by improving the antioxidative power, Those who feel poor sleep, those who want to reduce the physical fatigue caused by daily life and exercise, those who feel daily stress, those who feel transient stress due to psychologically burdensome work, those who feel memory Those who feel deterioration, those who feel deterioration of cognitive function, those who want to improve memory accuracy, those who want to maintain memory, those who want to make skin color whiter, those who want to reduce skin stains, those who want to improve liver function, those who are hungry Labels for those who want to improve the blood glucose level at times and after meals, those who want to improve constipation, those who want to improve the intestinal environment such as intestinal flora, those who want to improve immunity, etc. can be mentioned.

In the case of labeling for the purpose of anti-arteriosclerosis, there is no limitation, but for example, those who are concerned about LDL (bad) cholesterol, those who want to reduce LDL (bad) cholesterol, those with high cholesterol, etc. Can be mentioned.

In the case of labeling for the purpose of anti-allergy, there is no limitation, but for example, those who are concerned about eye fatigue, those who want to adjust the condition of the eyes, those who tend to have dry skin, those who want to adjust the condition of the skin. The display etc. toward the above can be mentioned.

Foods include all foods, such as grains, potatoes, fish and shellfish, meats, eggs, fats and oils, milk, vegetables, legumes, fruits, sugars, seaweeds, confectionery, seasonings. Kind, cooked processed foods and the like.

The seasoned processed foods are not limited, but for example, processed marine products such as chikuwa and kamaboko; processed livestock products such as ham and sausage; sweets such as cookies, biscuits, snacks, chocolates and cakes; soba, udon and raw noodles. , Chinese noodles, noodles such as pasta; bread such as bread and sweet bread; fermented processed foods such as natto and miso; soybean foods such as tofu and okara; pickles such as lightly pickled and rice bran pickles, marine products, processed meats, vegetables, Canned fruits and the like; dairy products such as butter, margarine, yogurt, cheese and milk; ice cream, chilled foods such as sherbet and the like.

Beverages include, but are not limited to, all beverages, such as fruit beverages, 100% fruit juice beverages, low fruit juice beverages, fruit meat beverages, vegetable juices, flavored beverages, diluting fruit beverages, and other fruit beverages; carbonated beverages. ; Favorite beverages such as coffee, coffee beverages, soft beverages with coffee, cocoa beverages, tea, green tea, matcha, crow dragon tea, barley tea, roasted tea; vinegared beverages; soft beverages such as sports drinks; milk; milk beverages; dairy beverages; Lactic beverages; Lactobacillus beverages; Soybean beverages such as soymilk and prepared soymilk; Alcoholic beverages such as beer, Japanese sake, shochu, liqueur, and wine; Nutritional beverages containing taurine, royal jelly, amino acids, vitamins, minerals, iron, and the like.

There is no limitation on the time when the present invention is applied to food and drink, but it can be applied, for example, before and after the processing step, cooking step, heating step, storage step and the like in the manufacturing process of food and drink. For example, in a processing step or a cooking step, the oral composition of the present invention can be included in the raw material. The application method can be appropriately changed depending on the type of food and drink, the form of the raw material, and the like, and various methods such as mixing, addition, coating, spraying, and dipping can be adopted.

When the present invention is applied to food and drink products, it is possible to appropriately add an auxiliary agent used in ordinary foods and beverages as long as the effects of the present invention are not impaired. Such auxiliaries include, for example, glucose, sucrose, fructose, oligosaccharide, water candy, maltose, multitose, xylitol, sorbitol, aspartame, sucralose, stebioside, rubusoside, corn syrup, corn starch, lactose, citric acid, tartrate, etc. Apple acid, succinic acid, lactic acid, L-ascorbic acid, dL-α-tocophenol, sodium erythorbate, glycerin, glycerin fatty acid ester, propylene glycol, polyglycerin fatty acid ester, sucrose fatty acid ester, propylene glycol fatty acid, sorbitol fatty acid ester , Esther Arabia gum, casein, pectin, gelatin, agar, carrageenan, vitamin Bs, vitamin Cs, vitamin Es, nicotinic acid amides, calcium pantothenate, calcium salts, amino acids, pigments, fragrances, preservatives, etc. Be done.

When the present invention is applied to a beverage product, the pH is appropriately adjusted depending on the type of the beverage product, and can be, for example, pH 2.0 to 7.5, preferably 2.5 to 7.2. .0 to 7.0 is more preferable, and 3.0 to 6.5 is even more preferable. The pH of the beverage product can be adjusted by appropriately blending, for example, sodium hydrogen carbonate, citric acid and its salts, gluconic acid and its salts, phosphoric acid and its salts, adipic acid and its salts and the like.

[Pharmaceuticals, quasi-drugs]
When the oral composition of the present invention is a drug or a quasi-drug, it can be formulated into an appropriate form and administered to humans or animals.

The oral composition of the present invention is formulated by a known method into a dosage form such as a tablet, a capsule, a granule, a syrup, a powder, a film, a drop, a jelly, or a semi-solid pudding. To. The oral composition of the present invention can be ingested without water due to a film-like, drop-like, jelly-like, semi-solid pudding-like dosage form or the like.

As one aspect of the dosage form, a known drug delivery system is utilized to enhance the stability and bioavailability of the oral composition of the present invention, or to improve the patient's medication compliance, or for a combined purpose. It is possible to deliver the oral composition of the present invention to the absorption site.

The drug delivery system utilizes, but is not limited to, polymers such as cellulose, dextran, starch, polyvinyl alcohol, acetylated or methylated polymers, polylactic acid and polyglycolic acid and their block copolymers, polyethylene glycol and the like. Methods, methods using transport proteins such as albumin, and other methods using micelles, liposomes, microspheres, nanoparticles, composite emulsions, dendrimers and the like can be mentioned. These drug delivery systems can be used not only for the purpose of transporting the oral composition of the present invention to a target site such as an absorption site, but also for the purpose of release control for releasing the oral composition of the present invention in a timely manner.

The oral composition of the present invention contains excipients, lubricants, binders, disintegrants, sweeteners, pH regulators and the like in liquid formulations as long as the effects of the present invention are not impaired. In the above, it is possible to appropriately add a solvent, a solubilizing agent, a suspending agent, an tonicity agent, a buffering agent, a painlessing agent, a thickening agent, a sweetening agent, a pH adjusting agent and the like.

Examples of the excipient include lactose, sucrose, D-mannitol, glucose, starch, cornstarch, calcium carbonate, kaolin, crystalline cellulose, light anhydrous silicic acid and the like.

Preferable examples of the lubricant include, for example, talc, purified talc, colloidal silica, borax, polyethylene glycol and the like.

Examples of the binder include water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, bound cellulose, sucrose, D-mannitol, dextrin, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and hydroxypropyl starch. , Methyl cellulose, ethyl cellulose, shelac, calcium phosphate and the like.

Examples of the disintegrant include starch, dried starch, corn starch, carboxymethyl cellulose, carboxymethyl cellulose calcium, carmellose calcium, croscarmellose sodium, carboxymethyl starch sodium, sodium alginate, canten powder, sodium hydrogencarbonate, calcium carbonate, and lauryl sulfate. Examples include sodium, stearic acid monoglyceride, lactose and the like.

Examples of the solvent include water for injection, alcohol, propylene glycol, macrogol, sesame oil, corn oil and the like.

Examples of the solubilizing agent include polyethylene glycol, propylene glycol, D-mannitol, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate and the like.

Examples of the suspending agent include surfactants such as stearyltriethanolamine, sodium lauryl sulfate, laurylaminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, and glycerin monostearate, and for example, polyvinyl alcohol and carboxy. Examples thereof include hydrophilic polymers such as sodium methylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose.

Examples of the tonicity agent include sodium chloride, glycerin, D-mannitol and the like.

Examples of the buffering agent include buffer solutions such as phosphates, acetates, carbonates and citrates.

Examples of the soothing agent include benzyl alcohol and the like.

Examples of the preservative include paraoxybenzoic acid esters, chlorobutanol, benzyl alcohol, phenethyl alcohol, dehydroacetic acid, sorbic acid and the like.

The effective dose of (A) poorly soluble polyphenol when the oral composition of the present invention is administered is not limited, but is generally 0.00001 to 5000 mg / day for humans and animals in terms of solid content. The body weight is kg, preferably 0.01 to 200 mg / kg body weight, and more preferably 0.1 to 100 mg / kg body weight. The number of administrations is usually 1 to 6 times a day, preferably 1 to 2 times a day, but can be appropriately adjusted depending on the administration route and the like.

In another aspect of the present invention, an oral composition containing polymethoxyflavonoids and (B) 1-vinyl-2-pyrrolidone polymer can be provided. (B) Polyvinylpyrrolidone, which is a 1-vinyl-2-pyrrolidone polymer, is a component having a poor recovery rate as compared with polymethoxyflavonoids alone. Surprisingly, it was found that the recoverability of the composition was significantly improved by coexistence with the class. The types, contents, and doses of the polymethoxyflavonoids, and the types, contents, and doses of the (B) 1-vinyl-2-pyrrolidone polymer are the same as described above. The oral composition containing the polymethoxyflavonoids and the (B) 1-vinyl-2-pyrrolidone polymer further contains the above-mentioned components (C) and (D) as long as the recoverability effect is not affected. It is possible.

Next, the present invention will be specifically described with reference to Examples, but the present invention is not limited to the following Examples.

[Test Example 1] Evaluation of recoverability 1
Each composition shown in Tables 1 to 4 was weighed on a weighing dish (balance tray uncharged, manufactured by AS ONE) and mixed uniformly with a spatula. The compositions shown in Table 1 used a weighing dish having a capacity of 10 mL, and the compositions shown in Tables 2 to 4 used a weighing dish having a capacity of 150 mL. After dropping the composition on the spatula onto a weighing pan, the weighing pan was tilted to slide the composition and spread evenly on the bottom surface. Next, in order to drop the composition from the weighing dish, the composition was placed upside down so that the bottom surface of the weighing dish faced down, and the upper surface of the weighing dish was tapped 5 times with the index finger to remove the composition. Then, the weight of the weighing pan was measured. The proportion of the composition recovered from the weighing pan was calculated by [Formula 1-1] (recovery rate). Next, the change in the recovery rate with respect to the corresponding comparative example was calculated by [Equation 1-2], and the results are shown in Tables 1 to 4. The corresponding comparative examples are Comparative Example 1-1 in Table 1, Comparative Example 2-1 in Table 2, Comparative Example 3-1 in Table 3, and Comparative Example 4-1 in Table 4. Since the corresponding comparative examples and examples were performed under the same environmental conditions, they were tested on the same day.
[Formula 1-1] Recovery rate (%) = (Weight of the weighing pan after removing the weighed composition-Empty weight of the weighing pan before weighing the composition) / Total weight of the weighed composition x 100
[Formula 1-2] Change in recovery rate (%) = (recovery rate of each composition)-(recovery rate of corresponding comparative example)

As shown in Tables 1 to 3, the recovery rate deteriorates when (B) polyvinylpyrrolidone, which is a 1-vinyl-2-pyrrolidone polymer, is added to (A) the sparingly soluble polyphenols curcumin, hesperidin, and resveratrol. New problems were found (Comparative Example 1-2, Comparative Example 2-2, Comparative Example 3-2). On the other hand, surprisingly, it was confirmed that the recovery rate was improved when any one of curcumin, hesperidin, and resveratrol was contained together with polyvinylpyrrolidone and cyclodextrin (Example 1-1, Examples 2-1 and 3-1 to 3-3). That is, it was confirmed that the oral composition of the present invention can be efficiently produced with a high recovery rate at the time of production by coexisting the above-mentioned component (A), component (B), and component (C). Further, when (D) magnesium stearate as a stearate or l-menthol as a terpenoid was added, the recovery rate was further significantly improved (Examples 1-2 to 1-3, Examples 2-2-2). -3, Examples 3-4 to 3-5).

As shown in Table 4, polyvinylpyrrolidone, which is a polymer of (B) 1-vinyl-2-pyrrolidone, is a component having a poor recovery rate as compared with polymethoxyflavonoids alone, but (A) a sparingly soluble polyphenol. Of these, coexistence with polymethoxyflavonoids (nobiletin in Table 4) surprisingly showed a remarkable improvement in the recovery rate of the composition (Examples 4-1 to 4-2).

[Test Example 2] Evaluation of recoverability 2
Each composition shown in Table 5 was weighed on a weighing dish and mixed uniformly with a spatula (spoon (stainless steel) 180 mm, manufactured by AS ONE Corporation). In the mixing operation, in order to keep the contact area between the spatula and the composition constant, the composition was touched up to 1 cm from the top of the spatula. After tapping the handle of the spatula with the index finger 5 times to remove the composition, the weight of the spatula was measured. The ratio of the composition recovered from the spatula was calculated by [Formula 2-1] (recovery rate). Next, the change in the recovery rate with respect to Comparative Example 5-1 was calculated by [Equation 2-2], and the results are shown in Table 5.
[Formula 2-1] Recovery rate (%) = (Weight of the spatula after mixing the composition-Weight of the spatula before mixing the composition) / Total weight of the weighed composition × 100
[Formula 2-2] Change in recovery rate (%) = (recovery rate of each composition)-(recovery rate of corresponding comparative example)

As shown in Table 5, recovery is achieved by adding polyvinylpyrrolidone, which is a (B) 1-vinyl-2-pyrrolidone polymer, which has a poor recovery rate as compared with resveratrol, to resveratrol, which is a poorly soluble polyphenol. The rate improved significantly (Example 5-1). That is, it was confirmed that the oral composition of the present invention can be efficiently produced with a high recovery rate at the time of production by coexisting the above-mentioned component (A), component (B), and component (C).

[Test Example 3] Evaluation of dispersibility 1
Each composition shown in Table 6 was stirred with a stirrer (500 rpm, 15 minutes, room temperature) to prepare a test solution. Each test solution was filled in a test tube with a glass screw cap by 8 mL each, and the turbidity immediately after stirring and after standing for 8 minutes was measured using a turbidity meter (manufactured by HACH). Specifically, immediately before the measurement, the test tubes were inverted and mixed, and vortexed for 1 minute. The turbidity of the test solution near the center of the test tube in the vertical direction was measured. The turbidity was measured three times for one test solution, and the average value of the three times was taken as the turbidity value of the test solution. From [Equation 3-1], the turbidity value after standing for 8 minutes with respect to the turbidity value immediately after stirring was calculated and used as the dispersion rate of each test solution. Next, the variance improvement rate for the corresponding comparative example was calculated by [Equation 3-2], and the results are shown in Table 6. The corresponding comparative examples are Comparative Example 6-1 for Examples 6-1 to 6-2 and Comparative Examples 6-2 to 6-3, and Examples 6-3 to 6-4 and Comparative Example 6-. Reference numeral 5 is Comparative Example 6-4.
[Equation 3-1] Dispersion rate (%) = (turbidity value after standing) / (turbidity value immediately after stirring) × 100
[Equation 3-2] Dispersion improvement rate (%) = (dispersion rate of each test solution)-(dispersion rate of corresponding comparative example)

As shown in Table 6, when (B) polyvinylpyrrolidone, which is a 1-vinyl-2-pyrrolidone polymer, was added to (A) curcumin, which is a sparingly soluble polyphenol, the dispersion improvement rate deteriorated (Comparative Example 6-2, Comparative Example 6-5). Moreover, when (C) cyclodextrin was added to curcumin, the dispersion improvement rate deteriorated (Comparative Example 6-3). On the other hand, it was confirmed that when curcumin, polyvinylpyrrolidone and cyclodextrin were contained together, the dispersion improvement rate was improved and the dispersion stability was enhanced (Examples 6-1 to 6-4). That is, it was confirmed that the oral composition of the present invention can be efficiently produced with high quality uniformity at the time of production by coexisting the above-mentioned component (A), component (B), and component (C). ..

[Test Example 4] Evaluation of dispersibility 2
Each composition shown in Tables 7 and 8 was prepared in the same manner as in Test Example 3 and used as a test solution. The dispersion improvement rate was determined by the same method as in Test Example 3. The results are shown in Tables 7 and 8. The corresponding comparative examples of [Equation 3-2] are Comparative Examples 7-1 for Examples 7-1 to 7-2 and Comparative Examples 7-2 to 7-4, and are compared with Examples 7-3. Example 7-6 is Comparative Example 7-5, Example 7-4 and Comparative Example 7-8 are Comparative Example 7-7, and Examples 7-5 and Comparative Example 7-10 are Comparative Examples. 7-9.

As shown in Tables 7 and 8, when (B) polyvinylpyrrolidone, which is a 1-vinyl-2-pyrrolidone polymer, is added to (A) the sparingly soluble polyphenols hesperidin, resveratrol, or nobiletin, the dispersion improvement rate is increased. It deteriorated (Comparative Example 7-2, Comparative Example 7-4, Comparative Example 7-6, Comparative Example 7-8, Comparative Example 7-10). Further, when (C) cyclodextrin was added to (A) hesperidin, which is a poorly soluble polyphenol, the dispersion improvement rate deteriorated (Comparative Example 7-3). On the other hand, it was confirmed that when any one of hesperidin, resveratrol, and nobiletin was contained together with polyvinylpyrrolidone and cyclodextrin, the dispersion improvement rate was improved and the dispersion stability was enhanced (Example 7-). 1 to Examples 7-5).

[Test Example 5] Evaluation of solubility 1
Each composition shown in Table 9 was prepared by shaking and stirring (100 straws / min) and used as a test solution. Next, 25 mL of each test solution was sealed in a centrifuge tube and allowed to stand in an incubator at 37 ° C. for 24 hours. Then, each test liquid was subjected to centrifugal sedimentation treatment for 5 minutes (15000 rpm), the supernatant liquid was filtered through a filter having a pore size of 0.2 μm, and the amount of curcumin dissolved in the filtered liquid was measured by high performance liquid chromatography. The solubility improvement rate of the curcumin-dissolved amount of each test solution with respect to the curcumin-dissolved amount of Comparative Example 8-1 was calculated by the following [Formula 4], and the results are shown in Table 9.
[Formula 4] Solubility (%) = (curcumin dissolution amount of test solution-curcumin dissolution amount of Comparative Example 8-1) / curcumin dissolution amount of Comparative Example 8-1 × 100

As shown in Table 9, the test solution containing (A) curcumin, which is a sparingly soluble polyphenol, and (B) polyvinylpyrrolidone, which is a 1-vinyl-2-pyrrolidone polymer, contains curcumin and (C) cyclodextrin. The improvement rate of curcumin solubility was lower than that of the test solution to be used, and the solubility was poor (Comparative Example 8-2 to Comparative Example 8-4). When curcumin, polyvinylpyrrolidone and cyclodextrin were contained together, the solubility improvement rate was significantly improved. That is, in the composition of the present invention, it is expected that the solubility of the component (A) is improved, the uniformity of quality is high, and the action of the component (A) is effectively exhibited.

[Test Example 6] Evaluation of solubility 2
A solution prepared by dissolving 0.2 g of curcumin in 200 mL of ethanol and a solution prepared by dissolving 2 g of polyvinylpyrrolidone K30 and 2 g of α-cyclodextrin in 200 mL of water were mixed and stirred, and then ethanol was removed using a rotary evaporator. The obtained liquid was spray-dried. Specifically, a spray-drying treatment was performed at a supply air temperature of 120 to 160 ° C. and an exhaust temperature of 50 to 70 ° C. using a spray-drying device. Water was added to the recovered dry solid to prepare a clear test solution. Next, 25 mL of the test solution was sealed in a centrifuge tube and allowed to stand in an incubator at 37 ° C. for 24 hours. Then, the test solution was subjected to centrifugal sedimentation treatment for 5 minutes (15000 rpm), the supernatant was filtered through a filter having a pore size of 0.2 μm, and the amount of curcumin dissolved after filtration was measured by high performance liquid chromatography. The results immediately after preparation (0 hours) and after standing for 24 hours (24 hours) are shown in FIG.

As shown in FIG. 1, the curcumin concentration of the test solution did not change between after the static treatment at 37 ° C. for 24 hours and immediately after the preparation. That is, by spray-drying the composition of the present invention, high solubility can be maintained even in long-term storage, and the action of curcumin can be effectively exerted for a long period of time.

[Test Example 7] Evaluation of Elution As shown in Table 10, a test solution containing curcumin, polyvinylpyrrolidone and cyclodextrin was prepared. As for the preparation method, Example 9-1 was stirred in the same manner as in Test Example 5, and Example 9-3 was subjected to spray-drying treatment after evaporation as in Test Example 6. Example 9-2 was prepared from Example 9-3 by a preparation method in which only evaporation was not performed. Next, the elution of curcumin was evaluated according to the paddle method of the dissolution test of the 16th revised Japanese Pharmacopoeia. Specifically, 900 mL of water was stirred at a paddle rotation speed of 50 rpm using a Japanese Pharmacopoeia elution tester, and each example was added so as to contain 5 mg of curcumin. After charging, sampling was performed over time, and the amount of curcumin elution was measured using high performance liquid chromatography. FIG. 2 shows the time required for the amount of curcumin elution to reach 0.5 μg / mL.

As shown in FIG. 2, curcumin was eluted earlier in Example 9-2, which was spray-dried than in Example 9-1 with stirring. In Example 9-3, which was evaporated and spray-dried, curcumin was eluted earlier and the elution property was significantly enhanced. It was confirmed that by subjecting the composition of the present invention to evaporation or spray-drying, the composition is quickly eluted in the living body and quickly absorbed, so that the absorbability is improved.

[Manufacturing Examples 1 to 9]
Using known techniques, oral compositions were prepared for the production examples listed in Tables 11-12. Production Examples 1 and 2 are tablets, Production Examples 3 and 4 are granules, Production Example 5 is a soft capsule, Production Examples 6 to 7 are jelly agents, and Production Examples 8 to 9 are liquid preparations.

Claims (7)

It contains (A) poorly soluble polyphenols, (B) 1-vinyl-2-pyrrolidone polymer, and (C) cyclodextrin .
A solid oral composition having a total content of the component (B) of 1 to 10 parts by weight based on 1 part by weight of the total content of the component (A) (provided that resveratrol, hydroxypropyl-. (Excluding pill-like oral compositions containing β-cyclodextrin and polyvinylpyrrolidone). The oral composition according to claim 1, further comprising (D) at least one selected from the group consisting of stearate and terpenoids. The oral composition according to claim 1 or 2 , wherein the total content of the component (A) is 0.00001w / v% to 90w / v%. The invention according to any one of claims 1 to 3 , wherein the total content of the component (C) is 0.0000001 to 10000 parts by weight with respect to 1 part by weight of the total content of the component (A). Oral composition. The oral composition according to any one of claims 1 to 4 , which is in the form of a powder, a tablet, a granule, or a capsule. A solid oral composition containing nobiletin and (B) 1-vinyl-2-pyrrolidone polymer. It comprises containing (A) a sparingly soluble polyphenol, (B) a 1-vinyl-2-pyrrolidone polymer, and (C) a cyclodextrin.
Here, a method for producing a solid oral composition, wherein the total content of the component (B) is 1 to 10 parts by weight with respect to 1 part by weight of the total content of the component (A). Except when producing a pill-like oral composition containing resveratrol, hydroxypropyl-β-cyclodextrin, and polyvinylpyrrolidone).

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