Oral composition

Abstract

To solve the following problem that a simpler method is strongly required in order to improve the bioavailability of taxifolin.SOLUTION: The problem is solved by providing an oral composition comprising: (A) taxifolin or a taxifolin-containing extract; and (B) at least one selected from the group consisting of Piper longum, an extract thereof, hydrogen, and a hydrogen-occluding mineral powder.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to an oral composition containing taxifolin or an extract containing taxifolin. [Background technology]

[0002] Taxifolin (3,5,7,3',4'-pentahydroxyflavanone), also known as dihydroquercetin, is a flavanol found in many plants, including larch, onion, and wine grapes (Vitis vinifera).

[0003] Taxifolin is extracted and optionally purified from such plants, and extracts containing taxifolin have been approved by the European Food Safety Authority (EFSA) and are being used and studied in Europe as a food ingredient for adults.

[0004] Taxifolin is known to have various physiological activities, including antitumor, antiviral, and antioxidant properties, and is expected to be used in health foods and functional cosmetics.

[0005] For example, Patent Document 1 proposes a composition for reducing stress, which contains taxifolin or a salt thereof as an active ingredient. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Publication No. 2023-062249 Summary of the Invention [Problem to be solved by the invention]

[0007] Taxifolin is known to have various physiological activities, but its bioavailability is low. Therefore, methods have been proposed to improve its bioabsorbability by encapsulating taxifolin in cyclic oligosaccharides (γ-oligosaccharides).

[0008] However, when preparing an inclusion complex or a composite, problems may arise in the formation rate and yield, and furthermore, the processing time and cost are required.

[0009] Therefore, there is a strong need for a simpler method to improve the bioavailability of taxifolin. [Means for solving the problem]

[0010] In order to solve the above problems, the inventors have made extensive research efforts and have unexpectedly discovered that bioavailability can be significantly improved by coexisting (A) taxifolin or an extract containing taxifolin with (B) at least one selected from the group consisting of pepper, an extract thereof, hydrogen, and mineral powder that occludes hydrogen, thereby completing the present invention.

[0011] That is, the present invention provides the formulations listed below.

[0012] [1] (A) taxifolin or an extract containing taxifolin, and (B) An oral composition containing at least one selected from the group consisting of long pepper, an extract thereof, hydrogen, and mineral powder that occludes hydrogen.

[0013] [2] The composition for oral administration according to [1], wherein the content of the component (B) is 0.03 to 10 parts by mass per part by mass of the component (A).

[0014] [3] The oral composition according to [1] or [2], further comprising (C) indigestible dextrin, wherein the content of the (C) component per 1 part by mass of the (A) component is more than 10 parts by mass.

[0015] [4] The composition for oral administration according to any one of [1] to [3], which has improved bioavailability.

[0016] [5] The composition for oral administration according to any one of [1] to [4], which is a food or drink, a medicine, a quasi-drug, or a pet food. [Effects of the Invention]

[0017] In one embodiment of the present invention, (A) taxifolin or an extract containing taxifolin can be coexisted with (B) at least one selected from the group consisting of pepper, an extract thereof, hydrogen, and mineral powder that occludes hydrogen, thereby significantly improving bioabsorbability. [Brief explanation of the drawings]

[0018] [Figure 1] Figure 1 shows the plasma taxifolin concentration in the following three groups: (1) Taxifolin (TX) group, (2) Taxifolin (TX) + long pepper extract group, and (3) Taxifolin (TX) + hydrogen powder group. [Figure 2] FIG. 2 is a graph showing an evaluation of the AUC (Area Under the Curve) calculated from the plasma taxifolin concentrations in FIG. [Figure 3] Figure 3 is a graph showing the evaluation of plasma taxifolin concentrations in the following five groups: (1) Taxifolin (TX) group, (2) Water-soluble taxifolin (TX1) group, (3) Water-soluble taxifolin (TX2) group, (4) Taxifolin (TX) + long pepper extract group, and (5) Water-soluble taxifolin (TX2) + long pepper extract group. [Figure 4] FIG. 4 is a graph showing an evaluation of the AUC (Area Under the Curve) calculated from the plasma taxifolin concentrations in FIG. DETAILED DESCRIPTION OF THE INVENTION

[0019] Hereinafter, embodiments of the present invention will be described, but these are merely examples of preferred modes for carrying out the present invention, and the present invention is not limited to these embodiments in any way.

[0020] [(A) Taxifolin or an extract containing taxifolin] Taxifolin (3,5,7,3',4'-pentahydroxyflavanone), also known as dihydroquercetin, is a type of flavanol and is represented by the following formula (1).

[0021] [ka] ···(1)

[0022] Taxifolin may be used as an extract from a plant containing taxifolin, or may be obtained by a known chemical synthesis method, or may be a commercially available product.

[0023] As used herein, the term "extract" includes an extract obtained from a plant as an extraction raw material, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, or any of these roughly purified or purified products.

[0024] Plants containing taxifolin are not particularly limited, but include, for example, plants belonging to the family Pinaceae, preferably plants belonging to the genus Larix or Pinus, and examples of plants in the genus Larix include Siberian larch (L. sibirica), Dahurian larch, European larch (L. decidua), L. kaempferi, L. gmelini, etc., and examples of plants in the genus Pinus include Siberian pine (P. sibirica), Scots pine (P. sylvestris), P. jezoensis, P. densiflora, P. thunbergii, etc. Other examples include plants in the family Juglandaceae, such as leaves of the evergreen tree Engelhardtia chrysolepis.

[0025] Examples of the parts of the plant belonging to the Pinaceae or Juglandaceae family to be extracted include wood and bark, and from the viewpoint of taxifolin content, wood including the cambium is preferred. The parts of the plant to be extracted may be in the state as collected, dried, or crushed or pulverized after drying. To achieve the most significant effects of the present invention, the parts of the plant to be extracted are preferably those collected within one week, but may also be those collected within three days, two days, or 24 hours.

[0026] The extraction method is not particularly limited, and known extraction methods can be used, but extraction methods using water, organic solvents, or mixed solvents thereof are preferred. Examples of solvents include water, lower aliphatic alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; polyhydric alcohols having 2 to 5 carbon atoms such as 1,3-butylene glycol, propylene glycol, and glycerin, or mixed solvents thereof. From the viewpoint of safety, water, ethanol, or mixed solvents thereof are more preferred.

[0027] Water that can be used as an extraction solvent includes pure water, tap water, well water, mineral water, hot spring water, spring water, fresh water, etc., as well as water that has been subjected to various treatments. Treatments that can be applied to water include, for example, purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering, etc., and also includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate-buffered physiological saline, etc.

[0028] The extraction time is not particularly limited, and examples include 1 hour or more, 2 hours or more, 3 hours or more, 4 hours or more, 5 hours or more, 6 hours or more, 10 hours or more, 12 hours or more, 15 hours or more, 24 hours or more, 2 days or more, 3 days or more, and 4 days or more. The extraction time may be, for example, within 7 days, within 5 days, within 4 days, within 3 days, within 2 days, within 24 hours, within 15 hours, within 12 hours, within 10 hours, within 8 hours, within 6 hours, within 5 hours, within 4 hours, within 3 hours, or within the range of 3 hours. Examples of extraction times include 1 hour to 2 days, 2 hours to 2 days, 3 hours to 2 days, 4 hours to 2 days, 5 hours to 2 days, 6 hours to 2 days, 1 hour to 1 day, 2 hours to 1 day, 3 hours to 1 day, 4 hours to 1 day, 5 hours to 1 day, 6 hours to 1 day, 1 hour to 15 hours, 2 hours to 15 hours, 3 hours to 15 hours, 4 hours to 15 hours, 5 hours to 15 hours, 6 hours to 15 hours, 1 hour to 12 hours, 2 hours to 12 hours, 3 hours to 12 hours, 4 hours to 12 hours, 5 hours to 12 hours, and 6 hours to 12 hours.

[0029] The extraction temperature is not particularly limited, and examples thereof include 30°C or higher, 40°C or higher, 50°C or higher, 60°C or higher, and 70°C or higher. Examples of extraction temperatures include 100°C or less, 98°C or less, 95°C or less, 90°C or less, 85°C or less, and 80°C or less. Examples of extraction temperatures include 30 to 100°C, 40 to 100°C, 50 to 100°C, 60 to 100°C, 70 to 100°C, 30 to 95°C, 40 to 95°C, 50 to 95°C, 60 to 95°C, 70 to 95°C, 30 to 90°C, 40 to 90°C, 50 to 90°C, 60 to 90°C, 70 to 90°C, 30 to 85°C, 40 to 85°C, 50 to 85°C, 60 to 85°C, 70 to 85°C, 30 to 80°C, 40 to 80°C, 50 to 80°C, 60 to 80°C, and 70 to 80°C.

[0030] In one embodiment of the extraction method, for example, the xylem or the xylem including the cambium of a plant containing taxifolin is collected, appropriately cut, and extracted by heating (e.g., 50 to 100°C) with water, ethanol, or aqueous ethanol. If necessary, the extract may be further concentrated and purified by distillation, recrystallization, or the like.

[0031] Taxifolin or an extract containing taxifolin may be further concentrated by treatment such as heating, or may be subjected to hot air drying (spray drying, etc.), freeze drying, reduced pressure heating drying, microwave drying, etc.

[0032] The extract containing taxifolin is not limited to, but preferably contains 80% or more taxifolin, and may also contain 85% or more taxifolin, 90% or more taxifolin, 92% or more taxifolin, 95% or more taxifolin, 98% or more taxifolin, or 99% or more taxifolin.

[0033] Commercially available taxifolin products include, for example, Vitarost (registered trademark, manufactured by Robios) and Labitol (registered trademark, manufactured by Amethyst).

[0034] In one embodiment, when taxifolin is used, the content of taxifolin alone in the composition is not particularly limited as long as the effects of the present invention are achieved, and examples thereof include 0.01% by mass or more, 0.05% by mass or more, etc., relative to the total amount of the composition. Examples of the content of taxifolin alone relative to the total amount of the composition include 5% by mass or less, 1% by mass or less, 0.5% by mass or less, etc. Examples of the content of taxifolin alone relative to the total amount of the composition include 0.01 to 5% by mass, 0.05 to 5% by mass, 0.01 to 1% by mass, 0.05 to 1% by mass, 0.01 to 0.5% by mass, 0.05 to 0.5% by mass, etc.

[0035] In another embodiment, the content of taxifolin alone is not limited and is set appropriately depending on the type, content, dosage form, etc. of other ingredients; for example, in the case of a solid composition, the content is preferably 0.1% by mass or more, more preferably 0.3% by mass or more, even more preferably 0.7% by mass or more, and particularly preferably 1% by mass or more, of the total amount of the composition. The content of taxifolin alone is, for example, preferably 95% by mass or less, more preferably 70% by mass or less, even more preferably 30% by mass or less, and particularly preferably 20% by mass or less, relative to the total amount of the composition. The content of taxifolin alone is, for example, preferably 0.1% by mass to 95% by mass, more preferably 0.3% by mass to 70% by mass, and even more preferably 0.7% by mass to 30% by mass, relative to the total amount of the composition.

[0036] In another embodiment, the content of taxifolin alone is not limited and is set appropriately depending on the type, content, dosage form, etc. of other ingredients; for example, in the case of a liquid composition, the content is preferably 0.001% by mass or more, more preferably 0.005% by mass or more, and even more preferably 0.01% by mass or more, relative to the total amount of the composition. The content of taxifolin alone is, for example, preferably 1.5% by mass or less, more preferably 1% by mass or less, and even more preferably 0.3% by mass or less, relative to the total amount of the composition. The content of taxifolin alone is, for example, preferably 0.001% by mass to 1.5% by mass, more preferably 0.005% by mass to 1.0% by mass, even more preferably 0.01% by mass to 0.3% by mass, and particularly preferably 0.02% by mass to 0.2% by mass, relative to the total amount of the composition.

[0037] In one embodiment, when an extract containing taxifolin is used, the content of the extract in the above composition is not particularly limited as long as the effects of the present invention are achieved, but examples include 0.1% by mass or more, 0.5% by mass or more, 1% by mass or more, etc., relative to the total amount of the composition. The content of the extract containing taxifolin relative to the total amount of the composition is, for example, 50% by mass or less, 10% by mass or less, or 5% by mass or less. The content of the extract containing taxifolin relative to the total amount of the composition may be, for example, 0.1 to 50% by mass, 0.5 to 50% by mass, 0.1 to 10% by mass, 0.5 to 10% by mass, 0.1 to 5% by mass, or 0.5 to 5% by mass.

[0038] [(B) Long Pepper, Long Pepper Extract, Hydrogen, Hydrogen-absorbing Mineral Powder] A commercially available product of taxifolin is a powder containing approximately 80% dihydroquercetin and other flavonoids, but the solubility of this product is even lower than taxifolin's solubility of 1 mg / ml at 25°C, and it cannot be said that it is sufficiently bioavailable.

[0039] By using the present invention, it is possible to significantly improve in vivo absorbability by coexisting (A) taxifolin or an extract containing taxifolin with (B) at least one selected from the group consisting of pepper, an extract thereof, hydrogen, and mineral powder that occludes hydrogen.

[0040] (Peppermint, Peppermint extract) Long pepper (Piper longum or Piper retrofractum) is a plant belonging to the genus Piper in the family Piperaceae, and is widely distributed in India, Southeast Asia, and other regions.

[0041] As the part of long pepper, for example, the whole plant or any necessary part (flower, inflorescence, flower bud, flower spike, leaf, branch, branch leaf, rhizome, root bark, root, bark, fruit, pericarp, fruit spike, legume, seed, etc.) can be used, with the fruit, fruit spike, or root being preferred, and the pulp or fruit spike being more preferred. The plant part of long pepper may be in the state as collected, dried, or crushed or pulverized after drying.

[0042] The extraction method for preparing the extract of long pepper is not particularly limited, and a known extraction method can be used, but a method similar to that described in [(A) Taxifolin or an extract containing taxifolin] may also be used. Commercially available products of long pepper or extract of long pepper may also be used.

[0043] Commercially available extracts of long pepper include, for example, dried long pepper GID-01 (manufactured by GOA International), dried long pepper fruit (manufactured by MK Laboratories), long pepper powder (manufactured by MK Laboratories), long pepper extract GIHO-04 (manufactured by GOA International), and long pepper extract (manufactured by Sabinsa Japan Corporation).

[0044] (Hydrogen, mineral powder that absorbs hydrogen) Hydrogen can be molecular hydrogen (i.e., gaseous hydrogen) or atomic hydrogen, and unless otherwise specified, molecular hydrogen is also simply referred to as "hydrogen" or "hydrogen gas." On the other hand, atomic hydrogen can also be referred to as "active hydrogen" or "negative hydrogen ions." In the chemical formula of molecular hydrogen, hydrogen can be H2, D2 (deuterium), HD (hydrogen deuteride), or a mixture of these. In the chemical formula of atomic hydrogen, H (active hydrogen), H - (negative hydrogen ions), and may be contained in the composition of the present invention as a gas or liquid containing molecular hydrogen or atomic hydrogen, or as a solid that generates molecular hydrogen or atomic hydrogen.

[0045] When a gas containing molecular hydrogen is used, the concentration of the hydrogen gas can be, for example, 0.5 to 18.5% by volume, and preferably 1 to 15% by volume, 1 to 10% by volume, 2 to 8% by volume, 2 to 9% by volume, 2 to 10% by volume, 3 to 6% by volume, 3 to 7% by volume, 3 to 8% by volume, 3 to 9% by volume, 3 to 10% by volume, 4 to 5% by volume, 4 to 6% by volume, 4 to 7% by volume, 4 to 8% by volume, 4 to 9% by volume, 4 to 10% by volume, 5 to 8% by volume, 5 to 9% by volume, 5 to 10% by volume, 6 to 7% by volume, 6 to 8% by volume, 6 to 9% by volume, 6 to 10% by volume, and the like.

[0046] When a liquid containing molecular hydrogen is used, for example, an aqueous liquid with hydrogen gas dissolved therein can be used. The aqueous liquid is not limited to, but examples thereof include water (e.g., purified water, sterilized water), physiological saline, etc.

[0047] When a liquid containing molecular hydrogen is used, the hydrogen concentration can be, for example, 1 to 10 ppm, and preferably 1.2 to 9 ppm, 1.5 to 9 ppm, 1.5 to 8 ppm, 1.5 to 7 ppm, 1.5 to 6 ppm, 1.5 to 5 ppm, 1.5 to 4 ppm, 2 to 10 ppm, 2 to 9 ppm, 2 to 8 ppm, 2 to 7 ppm, 2 to 6 ppm, 2 to 5 ppm, 3 to 10 ppm, 3 to 9 ppm, 3 to 8 ppm, 3 to 7 ppm, 4 to 10 ppm, 4 to 9 ppm, 4 to 8 ppm, 4 to 7 ppm, 5 to 10 ppm, 5 to 9 ppm, 5 to 8 ppm, 5 to 7 ppm, and the like.

[0048] When using a solid that generates molecular or atomic hydrogen, for example, a powder (such as hydrogen powder) that generates hydrogen upon contact with water can be used. When using hydrogen powder, examples of solids that generate atomic hydrogen include coral calcium that has absorbed hydrogen, and fossil shell powder such as oysters and scallops. In both cases, mineral powder rich in calcium, magnesium, and silica serves as the base for absorbing molecular or atomic hydrogen. Other examples of solids that generate molecular hydrogen include composite materials composed of "sunflower seed oil, potassium citrate, potassium carbonate, silica, magnesium sulfate, hydrogen" or "sodium bicarbonate, potassium carbonate, water-soluble silicon, potassium citrate, deep seawater powder, fine silicon dioxide, magnesium sulfate, and hydrogen."

[0049] The content of component (B) is not particularly limited as long as the effects of the present invention are achieved, but examples include 0.01 mass % or more, 0.05 mass % or more, and the like, based on the total amount of the composition. The content of the component (B) relative to the total amount of the composition is, for example, 5% by mass or less, 1% by mass or less, or 0.5% by mass or less. The content of the component (B) relative to the total amount of the composition may be, for example, 0.01 to 5 mass%, 0.05 to 5 mass%, 0.01 to 1 mass%, 0.05 to 1 mass%, 0.01 to 0.5 mass%, or 0.05 to 0.5 mass%.

[0050] The content of the (B) component per 1 part by mass of the (A) component is not particularly limited, but examples include 0.001 parts by mass or more, 0.005 parts by mass or more, 0.01 parts by mass or more, 0.03 parts by mass or more, 0.05 parts by mass or more, 0.1 parts by mass or more, 0.15 parts by mass or more, 0.2 parts by mass or more, and 0.3 parts by mass or more. The amount of the (B) component per 1 part by mass of the (A) component is, for example, 50 parts by mass or less, 40 parts by mass or less, 30 parts by mass or less, 20 parts by mass or less, 10 parts by mass or less, 5 parts by mass or less, 4 parts by mass or less, 3 parts by mass or less, 2.5 parts by mass or less, or 2 parts by mass or less. The content of the (B) component per 1 part by mass of the (A) component is not particularly limited, and may be, for example, 0.001 to 50 parts by mass, 0.01 to 50 parts by mass, 0.03 to 50 parts by mass, 0.05 to 50 parts by mass, 0.1 to 50 parts by mass, 0.15 to 50 parts by mass, 0.2 to 50 parts by mass, 0.3 to 50 parts by mass, 0.001 to 20 parts by mass, 0.01 to 20 parts by mass, 0.03 to 20 parts by mass, 0.05 to 20 parts by mass, 0.1 to 20 parts by mass parts, 0.15-20 parts by mass, 0.2-20 parts by mass, 0.3-20 parts by mass, 0.001-10 parts by mass, 0.01-10 parts by mass, 0.03-10 parts by mass, 0.05-10 parts by mass, 0.1-10 parts by mass, 0.15-10 parts by mass, 0.2-10 parts by mass, 0.3-10 parts by mass, 0.001-6 parts by mass, 0.01-6 parts by mass, 0.03-6 parts by mass, 0.05-6 parts by mass, 0.1-6 parts by mass, 0.15-6 parts by mass parts, 0.2-6 parts by mass, 0.3-6 parts by mass, 0.001-4 parts by mass, 0.01-4 parts by mass, 0.03-4 parts by mass, 0.05-4 parts by mass, 0.1-4 parts by mass, 0.15-4 parts by mass, 0.2-4 parts by mass , 0.3-4 parts by mass, 0.001-3 parts by mass, 0.01-3 parts by mass, 0.03-3 parts by mass, 0.05-3 parts by mass, 0.1-3 parts by mass, 0.15-3 parts by mass, 0.2-3 parts by mass, 0.3-3 parts by mass, 0 .001-2.5 parts by mass, 0.01-2.5 parts by mass, 0.03-2.5 parts by mass, 0.05-2.5 parts by mass, 0.1-2.5 parts by mass, 0.15-2.5 parts by mass, 0.2-2.5 parts by mass, 0.3-2.5 Parts by mass, 0.001-2 parts by mass, 0.01-2 parts by mass, 0.03-2 parts by mass, 0.05-2 parts by mass, 0.1-2 parts by mass, 0.15-2 parts by mass, 0.2-2 parts by mass, 0.3-2 parts by mass, and the like.

[0051] [(C) Indigestible dextrin] Although not limited thereto, the composition of the present invention may further contain (C) indigestible dextrin.

[0052] Resistant dextrin refers to a polysaccharide that is resistant to hydrolysis by human digestive enzymes (amylase). Resistant dextrin can be obtained, for example, by hydrolyzing starch by heating, followed by amylase, and purifying the resistant component. Thus, resistant dextrin may be obtained from starch or the like as a raw material, or a commercially available product in the form of powder, fine granules, granules, or the like may be used.

[0053] When the composition of the present invention contains (C) indigestible dextrin, from the viewpoint of significantly achieving the effects of the present invention, the content of the (C) component per 1 part by mass of the (A) component is preferably, for example, more than 10 parts by mass, and can be 11 parts by mass or more, 12 parts by mass or more, 13 parts by mass or more, 14 parts by mass or more, 15 parts by mass or more, 16 parts by mass or more, 17 parts by mass or more, 18 parts by mass or more, 19 parts by mass or more, 20 parts by mass or more, etc. The amount of the component (C) per 1 part by mass of the component (A) is, for example, 50 parts by mass or less, 45 parts by mass or less, 40 parts by mass or less, 35 parts by mass or less, or 30 parts by mass or less.

[0054] [Bioavailability] As described above, taxifolin has low bioavailability, and even if taken as is, it is difficult to obtain the various physiological activities inherent to taxifolin. Although inclusion complexation techniques using cyclic oligosaccharides have been proposed, the processing time and costs required are insufficient. Therefore, there has been a strong demand for a simpler method to improve the bioavailability of taxifolin.

[0055] In the following examples, it has surprisingly been demonstrated that the bioavailability of component (A) can be significantly improved by coexisting (A) taxifolin or an extract containing taxifolin with (B) at least one selected from the group consisting of long pepper, an extract thereof, hydrogen, and mineral powder that occludes hydrogen.

[0056] The composition of the present invention can be added to or mixed with beverages, foods, pharmaceuticals, feed, or pet foods. Alternatively, it can be used as a beverage, food, pharmaceutical, feed, or pet food as is. Because the composition of the present invention can significantly improve the bioavailability of taxifolin, it can be used as a food or beverage that explicitly or implicitly claims the physiological activity, etc., inherent to taxifolin as a functional property, i.e., health foods, functional foods, foods for patients, and foods for specified health uses. Furthermore, even if the functional property is not explicitly or implicitly claimed, it can be used as a so-called doctor's supplement provided by doctors at hospitals and / or clinics.

[0057] Health foods, functional foods, foods for patients, and foods for specified health uses can be used in various dosage forms, such as liquid preparations (drinks, syrups, suspensions), solid preparations (tablets, orally disintegrating tablets, granules, fine granules, powders, capsules, chewable tablets, candies, etc.), and liquid diets. Food preparations can be produced in the same manner as known food preparations and pharmaceutical preparations, and can be produced, for example, by mixing an active ingredient with excipients acceptable for food use and then using conventional means. The dosage form is not limited, but from the perspective of single oral administration, it is preferable that liquid preparations be drinks, and solid preparations be capsules, tablets, or granules.

[0058] [pH] The pH of the formulation of the present invention is not limited and may be changed as appropriate depending on the type and content of the ingredients, the form of the product, etc. In the case of a liquid formulation, the pH is, for example, preferably 3.0 to 6.0, more preferably 3.0 to 5.5, and even more preferably 3.5 to 5.0. The pH of the formulation can be adjusted using a known pH adjuster.

[0059] Furthermore, food compositions can be produced by incorporating the preparation of the present invention into liquid beverages such as juices, fruit juice drinks, milk, dairy drinks, whey drinks, lactic acid bacteria drinks, tea drinks, alcoholic drinks, coffee drinks, carbonated drinks, soft drinks, water drinks, cocoa drinks, jelly drinks, sports drinks, and diet drinks; semi-solid foods such as pudding and yogurt; noodles, confectioneries, spreads, soups, and the like.

[0060] When the present invention is prepared as a food composition, various food additives may be blended in. Examples of food additives include antioxidants, colorants, flavorings, seasonings, sweeteners, acidulants, pH adjusters, quality stabilizers, and preservatives.

[0061] When the present invention is prepared as a feed, examples thereof include pet food, livestock feed, and fish feed. Such feed can be produced by mixing the preparation of the present invention with general feed, such as grains, cereals, bran, fish meal, bone meal, oils and fats, skim milk powder, whey, mineral feed, or yeast. The produced feed can be orally administered to general mammals, livestock, farmed fish, and pet animals.

[0062] When the present invention is prepared as a feed, the target organism is not particularly limited, but is preferably a mammal other than human, such as a platypus, echidna, opossum, quoll, kangaroo, aardvark, rock badger, elephant, armadillo, sloth, anteater, tree shrew, flying lemur, chimpanzee, rabbit, mouse, hedgehog, camel, wild boar, giraffe, deer, cow, goat, hippopotamus, whale, dolphin, horse, rhinoceros, tapir, bat, tiger, wolf, weasel, bear, seal, dog, or cat, more preferably a dog or cat.

[0063] When the present invention is used as feed, pet food, or the like, it may be given to the pet several times a day by adding it to the staple food, or it may be given as a snack at any time. [Example]

[0064] The present invention will be described below with reference to examples, but the scope of the present invention is not limited thereto. Unless otherwise specified, numerical values ​​such as "%" and "parts" represent numerical values ​​based on mass.

[0065] [Test Example 1. Taxifolin Administration Test (1)] Seven-week-old male Wistar rats (Japan SLC) were adjusted to have approximately the same average body weight and divided into the following groups (four rats per group). (1)TX (120mg / kg) group (2) TX (120 mg / kg) + long pepper extract (150 mg / kg) group (3) TX (120 mg / kg) + hydrogen powder (120 mg / kg) group

[0066] (Preparation of test substance) The test substances in each of the above groups were prepared as follows. (1) In the TX (120 mg / kg) group, 120 mg of taxifolin (manufactured by ROBIOS, derived from the wood of Siberian larch including the cambium, taxifolin content 92%, same below) was suspended in 10 mL of distilled water by conventional methods. (2) In the TX (120 mg / kg) + long pepper extract (150 mg / kg) group, taxifolin (manufactured by ROBIOS) and long pepper extract powder (manufactured by Maruzen Pharmaceuticals, long pepper extract content 10%) were suspended in purified water by a conventional method. The above-mentioned "150 mg / kg" indicates the dose of long pepper extract powder as dry solid content (same below). (3) In the TX (120 mg / kg) + Hydrogen Powder (120 mg / kg) group, taxifolin (manufactured by ROBIOS) and hydrogen powder (manufactured by San-O Corporation) were suspended in purified water by a standard method. The above "120 mg / kg" indicates the dose of taxifolin (the same applies below).

[0067] (Administration test) The above solutions of each test substance were stirred with a vortex mixer each time, and then forcibly administered intragastrically at 1.0 mL per 100 g body weight using a stomach tube (manufactured by Natsume Seisakusho).

[0068] (Blood sampling over time) After administration of each test substance, heparinized blood (120 μL) was collected from the orbital venous plexus at 15, 30, 60, 120, and 360 minutes. The collected blood was centrifuged (4°C, 3000 g, 10 minutes), and plasma (50 μL) was collected and stored frozen.

[0069] (Measurement of blood concentration of taxifolin) Using the above plasma samples, the blood concentration of taxifolin was measured by the following method.

[0070] Plasma sample preparation Sample plasma, calibration blank plasma, and quality control (QC) samples were removed from the freezer and thawed at room temperature. For taxifolin measurement, plasma samples (50 μl) from rats administered taxifolin were mixed with 250 units of β-glucuronidase in 0.2 M acetate buffer (pH 5.0) and incubated at 37°C for 2 hours with stirring. The taxifolin-containing plasma released by enzymatic hydrolysis was transferred to a 5 ml tapered tube and vortex-mixed with 3 ml of ethyl acetate at 1000 rpm for 10 minutes. The tube was centrifuged at 1000 g for 10 minutes. The upper phase was transferred to a 2 ml polypropylene tube and evaporated to dryness under a nitrogen stream at 45°C. The residue was dissolved in 1 ml of methanol, and 20 ml was injected directly into the RP-HPLC system.

[0071] Chromatography conditions HPLC analysis was performed at room temperature using a Shimadzu HPLC system. Configuration: Two LC20AD pumps, a DGU-20 A3 degasser, and an SPD-M20 A diode array detector Separation was performed using a YMC-Pack Pro C18 RS (5.0 μm, 150 mm × 4.6 mm) column (YMC Co., Ltd., Japan) and a GUARD CARTRIDGE (5.0 μm, 10 mm × 4.0 mm) column (YMC Co., Ltd., Japan) using the same adsorbent. LC Solution PC software (Shimadzu Corporation, Kyoto, Japan) was used for data analysis.

[0072] The mobile phase for gradient elution consisted of a two-solvent system: Solvent A, 0.03% (v / v) aqueous trifluoroacetic acid; Solvent B, acetonitrile. Gradient elution was performed as follows: 20% (v / v) solvent B was used for the first minute, then the proportion of solvent B was linearly increased to 40% over 10 minutes, increased to 100% over the next 10 minutes, and then reversed. The next 5 minutes were kept at the initial condition. The flow rate was 1 ml / min. UV detection was performed at 290 nm at room temperature.

[0073] Calibration curve Standard stock solutions of taxifolin (1.0 mg / ml) and biochanin A (IS, 0.212 mg / ml) were prepared separately in methanol. These solutions were stored at 4 ± 1°C away from light and were found to be stable for at least one month. For the calibration curve, seven concentrations of taxifolin solutions were prepared by diluting the stock solution. A series of solutions (1.0 ml of each concentration) were evaporated to dryness at 45°C under a stream of nitrogen gas. Then, 1.0 ml of drug-free plasma and 10 ml of IS solution were added. The calibration range was 0.03–5.0 mg of taxifolin per ml of plasma. Calibration standards were extracted and analyzed as described above. A calibration curve was constructed based on the peak area ratio (x) of taxifolin to IS and the spiked concentration (y) of taxifolin.

[0074] The results for the plasma taxifolin concentrations are shown in Figure 1. The evaluation results for the AUC (Area Under the Curve) calculated from the plasma taxifolin concentrations in Figure 1 are shown in Figure 2.

[0075] As shown in Figures 1 and 2, it was confirmed that the bioavailability can be significantly improved by coexisting (A) taxifolin or an extract containing taxifolin with (B) at least one selected from the group consisting of long pepper, its extract, hydrogen, and hydrogen-absorbing mineral powder. In Figure 1, the graph is organized from top to bottom as follows: TX + hydrogen powder group, TX + long pepper extract group, and TX group.

[0076] [Test Example 2. Taxifolin Administration Test (2)] Seven-week-old male Wistar rats (Japan SLC) were adjusted to have approximately the same average body weight and divided into the following groups (four rats per group). (1) Taxifolin (TX) group (2) Water-soluble taxifolin (TX1) group (3) Water-soluble taxifolin (TX2) group (4) Taxifolin (TX) + long pepper extract group (5) Water-soluble taxifolin (TX2) + long pepper extract group

[0077] (Preparation of test substance) The test substances in each of the above groups were prepared as follows. (1) In the TX (120 mg / kg) group, 120 mg of taxifolin (manufactured by ROBIOS, taxifolin content 92%) was added to 10 mL of distilled water and kept at 45°C for 10 minutes for dissolution. (2) In the water-soluble taxifolin (TX1) group, 1318.68 mg of water-soluble taxifolin (TX1) (composed of two components, taxifolin (TX) and indigestible dextrin, with 120 mg of taxifolin (TX) in a composition ratio of approximately 1:11) was dissolved in 10 mL of distilled water. The water-soluble taxifolin was powdered by spray drying according to standard methods (the same applies to the other components). (3) In the water-soluble taxifolin (TX2) group, 1318.68 mg of water-soluble taxifolin (TX2) (composed of three components: taxifolin (TX), indigestible dextrin, and arabinogalactan, of which 120 mg was taxifolin (TX). The composition ratio was approximately 1:5.5:5.5) was dissolved in 10 mL of distilled water. (4) In the taxifolin (TX) + long pepper extract group, 120 mg of TX (manufactured by ROBIOS, taxifolin content 92%) and 150 mg of long pepper extract were mixed in 10 mL of distilled water and dissolved by incubating in 45°C water for 20 minutes. (5) In the water-soluble taxifolin (TX2) + long pepper extract group, 1318.68 mg of water-soluble taxifolin (TX2) (composed of three components: taxifolin (TX), indigestible dextrin, and arabinogalactan, of which 120 mg of taxifolin (TX) was contained) and 150 mg of long pepper extract were mixed and dissolved in 10 mL of distilled water.

[0078] The administration test, blood sampling over time, measurement of taxifolin blood concentrations, and evaluation of AUC were performed in the same manner as in Test Example 1. The results of the taxifolin plasma concentrations in Test Example 2 are shown in Figure 3. The evaluation results of AUC calculated from the taxifolin plasma concentrations in Figure 3 are shown in Figure 4.

[0079] As shown in Figures 3 and 4, it was confirmed that the bioavailability can be significantly improved by coexisting (A) taxifolin or an extract containing taxifolin with (B) component. This effect was confirmed as a significant effect whether the formulation was in a suspension form or a water-soluble formulation with enhanced solubility.

[0080] Although the above mechanism is unclear, if it is assumed that the principle is blood flow promotion, it is predicted that a known blood flow promoter such as catechin can be used in combination, but when taxifolin and catechin were used in combination in a test similar to Test Example 1, no absorption-promoting effect was confirmed. Therefore, it has been confirmed that the effect of the present invention is not necessarily achieved solely through the mechanism of blood flow improvement (data not shown).

Claims

1. (A) taxifolin or an extract containing taxifolin, and (B) An oral composition containing at least one selected from the group consisting of long pepper, its extract, hydrogen, and mineral powder that occludes hydrogen.

2. 2. The oral composition according to claim 1, wherein the content of the component (B) is 0.03 to 10 parts by mass per 1 part by mass of the component (A).

3. 2. The oral composition according to claim 1, further comprising (C) an indigestible dextrin, wherein the content of the (C) component per 1 part by mass of the (A) component is more than 10 parts by mass.

4. 10. The oral composition of claim 1, which has improved bioavailability.

5. The oral composition according to claim 1, which is a food or drink, a medicine, a quasi-drug, or a pet food.

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