Absorption enhancer for flavonoids

Abstract

To provide an agent capable of promoting the absorption of flavonoids having a specific structure into the body.SOLUTION: An absorption enhancer for flavonoids into the body comprises propolis derived from Baccharis dracunculifolia, where the flavonoids are at least one selected from the group of compounds represented by the general formula (1) in the figure. (In the formula, R1, R2 and R3 are identical or different and each represent a hydrogen atom, a hydroxyl group, or a methoxy group.)SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an absorption enhancer for flavonoids. [Background technology]

[0002] Many natural flavonoids are known to have beneficial physiological activities for the human body, such as antioxidant and blood pressure lowering effects. However, many flavonoids are poorly water-soluble, so their transfer into the human body is low at about 0.1%, and the development of highly bioavailable flavonoids to express their physiological activities is a challenge.

[0003] Flavonoids are expected to be effective ingredients in foods and supplements, but taking large amounts of supplements can be a burden for consumers, so it is desirable to be able to efficiently absorb flavonoids into the body.

[0004] Methods to enhance the absorption of flavonoids include emulsification, particle size reduction, and combination with other ingredients. However, there are problems with the degradation of flavonoids during processing and high costs, so a method to enhance absorption that solves these problems is required.

[0005] Patent Document 1 reports an orally ingested quercetin bioabsorption enhancer that contains, as an active ingredient, HM pectin derived from apple or citrus and with a degree of methyl esterification of 50% or more. It also describes that a human test showed that when apple-derived pectin was administered, absorption was improved by about 70% compared to when it was not administered.

[0006] Propolis is a glue-like substance made by mixing tree sap, plant buds and exudates collected by honeybees with beeswax and other substances, and is known to have antibacterial, antioxidant, anti-inflammatory, antitumor and anti-allergic effects.

[0007] Since the components of propolis are influenced by the type and composition of the original plant from which it is made, it is known that the types and amounts of active ingredients contained in propolis, as well as their physiological activities, vary greatly depending on the country or region where it is harvested.

[0008] In recent years, research into the components of propolis from different origins has been progressing. For example, the main components of Brazilian propolis, which is derived from Baccharis duraclifolia, are p-coumaric acid, artepillin C, drupanin, baccharin, and other cinnamic acid derivatives. On the other hand, the main components of propolis from China, Europe, and Australia, which is derived from poplar, are flavonoids such as chrysin and galangin. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] Patent No. 5697834 Summary of the Invention [Problem to be solved by the invention]

[0010] An object of the present invention is to provide an agent capable of promoting absorption of a flavonoid having a specific structure into the body. [Means for solving the problem]

[0011] Since propolis is made from plants harvested by bees, the ingredients vary depending on the place of origin, and therefore it is expected that the effects of propolis vary depending on the place of origin. The present inventors have conducted intensive research to achieve the above-mentioned object, and have orally administered a mixture of propolis powder from Uruguay, which contains a large amount of flavonoids, and propolis powder derived from Baccharis duracunclifolia, and investigated the blood kinetics of flavonoids in humans. As a result, it was confirmed that the AUC of flavonoids (chrysin, galangin, pinocembrin) was improved by about 3.5, 2.0, and 2.4 times, and the Cmax was improved by about 6.2, 3.0, and 3.1 times in the mixed powder compared to the single powder. From these results, the propolis derived from Baccharis duracunclifolia was found to have the function of a flavonoid absorption enhancer, and the present invention was completed.

[0012] That is, the present invention relates to the following [1] to [5]. [1] An absorption enhancer for a flavonoid into the body, comprising propolis derived from Baccharis duraunclifolia, wherein the flavonoid is at least one selected from the group consisting of compounds represented by the following general formulas (1), (2) and (3).

[0013] [ka] (In the formula, R 1 , R 2 and R 3 are the same or different and represent a hydrogen atom, a hydroxyl group, or a methoxy group.

[0014] [ka] (In the formula, R 1 , R 2 and R 3 is the same as above)

[0015] [ka] (In the formula, R 1 , R 2 and R 3is the same as above) [2] The absorption enhancer described in [1], wherein the flavonoid is a flavonoid derived from poplar and / or a flavonoid derived from propolis originating from poplar. [3] The absorption enhancer described in [1] or [2], wherein the flavonoid is at least one selected from the group consisting of chrysin, galangin, and pinocembrin. [4] The absorption enhancer described in any one of [1] to [3], wherein the propolis derived from Baccharis duraunclifolia is a propolis ethanol extract. [5] The absorption enhancer according to any one of [1] to [4], which is a food or drink, a medicine, or a quasi-drug. Effect of the Invention

[0016] Propolis derived from Baccharis dura unclifolia has excellent absorption-promoting properties for flavonoids with specific structures, and is therefore useful as an active ingredient in absorption enhancers.

[0017] Moreover, since propolis has traditionally been used as a food ingredient, it is highly safe. [Brief description of the drawings]

[0018] [Figure 1] Graph showing the AUC (ng / mL·h) of chrysin, galangin and pinocembrin. Left: single powder of Uruguayan propolis powder, right: mixed powder of Uruguayan propolis powder + Baccharis duracunclifolia-derived propolis powder. Values ​​are mean ± standard deviation. [Diagram 2] Graph showing Cmax (ng / mL) of chrysin, galangin and pinocembrin. Left: single powder of Uruguayan propolis powder, right: mixed powder of Uruguayan propolis powder + Baccharis duracunclifolia propolis powder. Values ​​are mean ± standard deviation. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] Hereinafter, the embodiment for carrying out the present invention will be described in detail, however, the present invention is not limited to the following embodiment.

[0020] In this specification, the term "comprise" includes the meanings of "essentially consist of" and "consist only of."

[0021] The absorption enhancer of the present invention is an absorption enhancer of a flavonoid into the body, and contains propolis derived from Baccharis duracunclifolia. The flavonoid is at least one selected from the group consisting of compounds represented by the following general formulas (1), (2) and (3) (hereinafter, the flavonoid may be referred to as "the flavonoid of the present invention").

[0022] [ka] (In the formula, R 1 , R 2 and R 3 are the same or different and represent a hydrogen atom, a hydroxyl group, or a methoxy group.

[0023] [ka] (In the formula, R 1 , R 2 and R 3 is the same as above)

[0024] [ka] (In the formula, R 1 , R 2 and R 3 is the same as above)

[0025] Propolis is a resinous or waxy substance that constitutes the walls of beehives, and is made by mixing the buds or resins of plants that bees have collected with the saliva of bees. Propolis can be obtained, for example, as a beekeeping product in the usual way. The plant from which the propolis used in the present invention is derived is Baccharis dracunculifolia.

[0026] The propolis used in the present invention is not particularly limited as long as it is derived from the above-mentioned plants, and may be derived from any of the places of origin such as Brazil, China, Taiwan, European countries, Russia, Oceania, and America, among which Brazilian propolis (e.g., green propolis) is preferred. In addition, propolis derived from plants other than Baccharis duracunclifolia may be used in combination. Propolis may be used alone or in combination of two or more types.

[0027] The propolis in the present invention may be, for example, a propolis lump, or a processed propolis product obtained by subjecting a propolis lump to some kind of processing. The processed propolis may be, for example, a propolis lump that has been subjected to processing such as pulverization, extraction, extract concentration or powderization, powder granulation, or the like, or may be an extraction residue remaining after extraction. That is, the processed propolis may be, for example, a pulverized propolis, an extract, a concentrated extract, an extract powder, an extract granule, an extraction residue, or the like. The extraction may be, for example, water extraction, hydrophilic organic solvent extraction, supercritical extraction, or the like. Examples of hydrophilic organic solvents include ethanol, glycerin, and 1,3-butylene glycol. The propolis extract may be obtained by extraction from a propolis lump, or may be obtained by further extraction from the residue after extraction. In addition, the extraction solvent may be used alone, or two or more types may be arbitrarily combined to be used as a mixed solvent. The processing method may be one, or two or more may be combined. As the processed propolis, a propolis hydrophilic organic solvent extract is preferable because it is a product in which the effective components of propolis are extracted efficiently and in a well-balanced manner in a short time. The processed propolis is preferably a propolis ethanol extract.

[0028] The propolis extract includes the recovered extract (including further purified as necessary), the concentrated extract, and the solid obtained by removing the solvent from the extract by freeze-drying, spray-drying, etc. Here, the concentration, freeze-drying, and spray-drying of the extract can be carried out according to a conventional method. The propolis extract of the present invention also includes the powder obtained by powdering such an extract, and the granular form obtained by granulating the powder.

[0029] Commercially available propolis may be used. Specific examples of commercially available propolis include Yamada Bee Farm's Propolis 300, Propolis Liquid 30 (Brazilian), propolis granules, propolis granules APC, propolis mild, propolis drink, etc.

[0030] The content of propolis in the absorption enhancer of the present invention is not particularly limited as long as the effects of the present invention can be obtained, and can be appropriately adjusted depending on the final form, etc., and can be, for example, 0.00001 mass% or more, 0.0001 mass% or more, 0.001 mass% or more, 0.01 mass% or more, 0.1 mass% or more, 0.5 mass% or more, 1 mass% or more, 3 mass% or more, 5 mass% or more, 7 mass% or more, 10 mass% or more, 15 mass% or more, 20 mass% or more, 3 mass% or more, 4 mass% or more, 5 mass% or more, 6 mass% or more, 7 mass% or more, 8 mass% or more, 9 mass% or more, 10 mass% or more, 12 mass% or more, 14 mass% or more, 16 mass% or more, 18 mass% or more, 19 mass% or more, 20 mass% or more, 21 mass% or more, 22 mass% or more, 23 mass% or more, 24 mass% or more, 25 mass% or more, 26 mass% or more, 27 mass% or more, 28 mass% or more, 29 mass% or more, 30 mass% or more, 31 mass% or more, 32 mass% or more, 33 mass% or more, 34 mass% or more, 35 mass% or more, 36 mass% or more, 37 mass% or more, 38 mass% or more, 39 mass% or more, 40 mass% or more, 41 mass% or more, 42 mass% or more, 43 mass% or more, 44 mass% or more, 45 mass% or more, 46 mass% or more, 47 mass% or more, 48 mass% or more, 49 mass% or more, 50 mass% It may be 0 mass% or more, 40 mass% or more, 50 mass% or more, 60 mass% or more, 70 mass% or more, 80 mass% or more, or 90 mass% or more, and 100 mass% or less, 90 mass% or less, 80 mass% or less, 70 mass% or less, 60 mass% or more. Below, it may be 55% by mass or less, 50% by mass or less, 40% by mass or less, 30% by mass or less, 20% by mass or less, 15% by mass or less, 10% by mass or less, 7% by mass or less, 5% by mass or less, 3% by mass or less, 1% by mass or less, or 0.5% by mass or less.

[0031] Specific examples of flavonoids in the present invention include chrysin, apigenin, acacetin, luteolin, tectochrysin, genkwanin, chrysoeriol, diosmetin, galangin, kaempferide, kaempferol, isorhamnetin, quercetin, rhamnetin, pinocembrin, eriodictyol, hesperetin, naringenin, sakuranetin, isosakuranetin, sterubin, etc. The substituents in the general formulae (1), (2) and (3) in each compound are shown in Tables 1 to 3.

[0032] [Table 1]

[0033] [Table 2]

[0034] [Table 3]

[0035] The flavonoids in the present invention are preferably chrysin, galangin, and pinocembrin. The flavonoids may be used alone or in combination of two or more.

[0036] The flavonoid in the present invention includes both free and salt forms. Examples of salts include salts with inorganic bases such as sodium salts, potassium salts, magnesium salts, calcium salts, and aluminum salts; salts with organic bases such as methylamine, ethylamine, and ethanolamine; salts with basic amino acids such as lysine, ornithine, and arginine, and ammonium salts. The salts may be acid addition salts, and specific examples of such salts include salts with mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid; salts with organic acids such as formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, methanesulfonic acid, and ethanesulfonic acid; and salts with acidic amino acids such as aspartic acid and glutamic acid. In addition, the flavonoid in the present invention also includes its hydrates, solvates, and crystalline polymorphs.

[0037] The flavonoid in the present invention may be a synthetic product, or may be a natural product such as a plant or propolis containing the flavonoid in the present invention, either as is or after purification of the flavonoid. The plant containing the flavonoid in the present invention is not particularly limited, and may be, for example, poplar (genus Populus or Populus of the Salicaceae family). The propolis containing the flavonoid in the present invention is not particularly limited, and may be, for example, South American, Chinese, European, or Australian propolis originating from poplar.

[0038] The flavonoid in the present invention is preferably a flavonoid derived from poplar and / or a flavonoid derived from propolis originating from poplar. The flavonoid derived from poplar and propolis in this case includes not only isolated or purified flavonoids but also poplar and propolis containing the flavonoid in the present invention.

[0039] The part of poplar to be used is not particularly limited and can be appropriately selected, and examples thereof include flowers, fruits, leaves, buds, wood, roots, bark, sap, and mixtures thereof. Poplar may be either the poplar itself obtained by harvesting or a processed poplar product. Examples of processed poplar products include dried poplar, crushed poplar, crushed poplar, powder, and extract. Poplar can be dried by, for example, sun drying, hot air drying, freeze drying, spray drying, and the like. Crushing and crushing can be performed, for example, using a crusher, crusher, and the like, respectively. Poplar extracts can be prepared by a method commonly used for plant extraction. For example, the poplar extract can be prepared by putting the poplar extract part, which is the extraction raw material, into a treatment tank filled with an extraction solvent, dissolving the soluble components while stirring appropriately as necessary, and then filtering to remove the extraction residue. As the poplar extract, the extract obtained by extraction from poplar may be used as it is, or may be further treated (for example, diluted, concentrated, dried, filtered, purified, etc.).

[0040] The absorption enhancer may be administered together with the flavonoid, or the flavonoid may be administered within a certain time period of the absorption enhancer, for example within 1 hour or within 30 minutes.

[0041] The absorption enhancer of the present invention may further contain the flavonoid of the present invention in addition to the propolis derived from Baccharis duracunclifolia. It is preferable that the absorption enhancer contains both the propolis derived from Baccharis duracunclifolia and the propolis of the present invention, since it is easy to administer the propolis derived from Baccharis duracunclifolia and the flavonoid at the same time and in an appropriate ratio.

[0042] When the absorption enhancer contains a flavonoid of the present invention, the amount of each flavonoid represented by general formula (1), (2) or (3) contained in the absorption enhancer, or the total amount thereof, may be, for example, 0.001 mass% or more, 0.01 mass% or more, 0.1 mass% or more, 1 mass% or more, 3 mass% or more, 4 mass% or more, or 5 mass% or more, as a solid content, relative to the total amount of the absorption enhancer, and may be 10 mass% or less, 5 mass% or less, 3 mass% or less, 1 mass% or less, 0.1 mass% or less, or 0.01 mass% or less.

[0043] The mixing ratio of the propolis derived from Baccharis duracunclifolia and the flavonoid of the present invention in the absorption enhancer of the present invention is not particularly limited. When the flavonoid of the present invention is propolis, the mixing ratio (dry mass) of the propolis derived from Baccharis duracunclifolia contained in the absorption enhancer to the propolis containing the flavonoid may be, for example, 1:0.01-100, 1:0.1-10, 1:0.5-5, etc.

[0044] The absorption enhancer of the present invention can also be administered to humans, for example, to enhance the absorption of flavonoids in the body. The absorption enhancer of the present invention is suitable for oral administration.

[0045] The dosage of the absorption enhancer of the present invention when administered orally may vary depending on the form of the active ingredient, the composition, and the application method and amount, but for example, for an adult weighing 60 kg, the dosage may be 1 mg to 1,000 mg, preferably 100 mg to 500 mg, more preferably 200 mg to 500 mg, and even more preferably 300 mg to 400 mg, per day, calculated as the dry solid content of the active ingredient, propolis. The dosage may be increased or decreased as appropriate depending on factors such as the health condition of the person taking it, the administration method, the type of active ingredient, and the combination with other agents.

[0046] The absorption enhancer of the present invention may be administered once a day, or in multiple doses, such as twice or three times a day, as long as the effective daily dose is within the above-mentioned range. The absorption enhancer of the present invention is effective immediately after administration, but continuous administration for 1 to 4 weeks, or for one month or more, six months or more, or one year or more is preferable because the effect can be sustained longer.

[0047] The absorption enhancer of the present invention can be used as food and drink (particularly food and drink intended for health, maintaining or improving health, etc. (e.g., health foods, functional foods, nutritional compositions, dietary supplements, supplements, health foods, foods for specified health uses, foods with nutrient functions, or foods with functional claims)), quasi-drugs, medicines, etc. The absorption enhancer of the present invention also encompasses the meaning of an additive that imparts an absorption enhancing effect to flavonoids.

[0048] Foods and beverages, quasi-drugs, or pharmaceuticals containing the absorption enhancer of the present invention as one component can be produced, for example, by adding the absorption enhancer of the present invention to intermediate products in the manufacturing process of these products.

[0049] The propolis may be used as is in the above-mentioned foods and beverages, or may be mixed with minerals, vitamins, flavonoids, quinones, polyphenols, amino acids, nucleic acids, essential fatty acids, cooling agents, binders, sweeteners, disintegrants, lubricants, colorants, fragrances, stabilizers, gelling agents, preservatives, sustained-release regulators, surfactants, solubilizers, humectants, etc., as necessary.

[0050] Food and drink includes all foods and drinks that animals (including humans) can consume. The types of food and drink are not particularly limited, and examples thereof include dairy products, fermented foods (yogurt, etc.), beverages (soft drinks such as coffee, juice, and tea drinks, milk drinks, lactic acid bacteria drinks, drinks containing lactic acid bacteria, yogurt drinks, carbonated drinks, sake, Western liquor, and alcohol such as fruit wine, etc.), spreads (custard cream, etc.), pastes (fruit paste, etc.), Western confectionery (chocolate, donuts, pies, cream puffs, gum, gummies, jellies, candies, cookies, cakes, puddings, etc.), Japanese confectionery (daifuku, mochi, manju, castella, anmitsu, yokan, etc.), frozen desserts (ice cream, popsicles, sorbets, etc.), foods (curry, beef bowl, porridge, miso soup, soup, meat sauce, pasta, pickles, jam, etc.), and seasonings (dressing, furikake, umami seasoning, soup base, etc.).

[0051] The method for producing the food or drink is not particularly limited, and any known method can be used as appropriate.

[0052] The dosage unit form when used as a supplement is not particularly limited and can be selected as appropriate. Examples include tablets such as chewable tablets and lozenges, capsules, granules, liquids, powders, syrups, pastes, drinks, gummies, and the like.

[0053] The above-mentioned propolis can be used alone in the above-mentioned medicines, or can be mixed with other medicinal ingredients such as vitamins and herbal medicines listed in the Japanese Pharmacopoeia.

[0054] When the absorption enhancer of the present invention is prepared as a medicine, the propolis can be prepared together with a pharmaceutical acceptable ingredient into a form such as a tablet (including plain tablets, sugar-coated tablets, effervescent tablets, film-coated tablets, chewable tablets, troches, etc.), capsule, pill, powder (powder), fine granules, granules, liquid, suspension, emulsion, syrup, paste, etc. to prepare a pharmaceutical preparation. Oral administration is suitable for the administration of the medicine.

[0055] In addition to propolis, the pharmaceutical of the present invention may contain, as necessary, pharma- ceutically acceptable ingredients such as excipients, binders, disintegrants, lubricants, colorants, suspending agents, thickeners, antioxidants, absorption enhancers, pH adjusters, preservatives, stabilizers, surfactants, sweeteners, flavorings, and fragrances.

[0056] The pharmaceutical product of the present invention also includes quasi-drugs.

[0057] The absorption enhancer of the present invention described above is applied to mammals including humans (preferably humans).

[0058] The propolis derived from Baccharis duraunclifolia, which is contained as an active ingredient in the absorption enhancer of the present invention, has the effect of promoting the absorption of flavonoids having a specific structure into the body, as shown in the examples described below, and is therefore useful as an active ingredient in absorption enhancers.

[0059] Furthermore, the absorption enhancer of the present invention is highly safe since it uses propolis, which has been used as a food ingredient for a long time. EXAMPLES

[0060] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to the following examples.

[0061] Example 1 (Preparation of propolis powder) Preparation of propolis ethanol extract Baccharis duracunclifolia propolis ethanol extract: Brazilian propolis raw mass was mixed with 96% ethanol, stirred, filtered, and the residue was removed. The filtrate was then concentrated to a solid content of 80%. Uruguay-produced propolis ethanol extract: 80% ethanol was added to the raw propolis produced in Uruguay, and the solution was stirred, filtered, and the residue was removed.The filtrate was then concentrated so that the solid content in the filtrate was 67.5%. Preparation of propolis powder Baccharis duracunclifolia propolis powder: Baccharis duracunclifolia propolis ethanol extract was mixed with arginine and purified water and stirred. It was then freeze-dried to prepare Baccharis duracunclifolia propolis powder. Uruguay propolis powder: Arginine, dextrin, and purified water were added to the ethanol extract of Uruguay propolis and stirred.Then, the mixture was freeze-dried to prepare Uruguay propolis powder. Preparation of test meals The powder was ground in a mortar and pestle, visually confirmed to be uniformly mixed, and then filled into hard capsules.

[0062] Test Example 1 <Administration> Number of subjects 3 adult men and women ○Drinking amount Single powder: 363mg of Uruguayan propolis powder Mixed powder: 181.5mg Uruguay propolis powder + 181.5mg Baccharis duracunclifolia propolis powder ○Drinking method Drink with room temperature water <Blood collection> ○Blood collection time: Before drinking, 0.5, 1, 1.5, 3, 6, 9, 24 hours after drinking <Test Method> 〇Plasma collection Approximately 100 μL of blood was collected by finger puncture using a blood collection tube (Eiken E-DS1), and then centrifuged using a centrifuge (Eiken M-4L08) to collect plasma. Quantitative analysis of chrysin, galangin, and pinocembrin The concentrations of chrysin, galangin, and pinocembrin in the plasma were quantified using LC (Thermo ultimate3000) and MS (Thermo Q Exactive Focus). Calculation of maximum blood concentration (Cmax) and area under the curve (AUC) Cmax was defined as the maximum plasma concentration of each component at the time point after administration, and AUC was calculated by the linear trapezoidal method. Statistical analysis was performed by paired t-test.

[0063] <Result> The obtained AUC is shown in Figure 1, and Cmax in Figure 2. Propolis from Uruguay is a propolis derived from poplar and contains flavonoids such as chrysin, galangin, and pinocembrin. When propolis powder from Baccharis duracunclifolia was mixed with propolis powder from Uruguay and administered, the Cmax of chrysin, galangin, and pinocembrin were 6.23, 2.96, and 3.1 times higher, respectively, and the AUC was 3.49, 2.03, and 2.37 times higher, respectively, compared to administration of propolis powder from Uruguay alone. In addition, the AUC of galangin and pinocembrin showed a significant improvement in absorbability.

Claims

1. An absorption enhancer for a flavonoid into the body, comprising propolis derived from Baccharis duracunclifolia, wherein the flavonoid is at least one selected from the group consisting of compounds represented by the following general formulas (1), (2) and (3). 【Chemistry 1】 (In the formula, R １ , R ２ and R ３ are the same or different and represent a hydrogen atom, a hydroxyl group, or a methoxy group.) 【Chemistry 2】 (In the formula, R １ , R ２ and R ３ is the same as above) 【Chemistry 3】 (In the formula, R １ , R ２ and R ３ is the same as above)

2. The absorption enhancer according to claim 1 , wherein the flavonoid is a flavonoid derived from poplar and / or a flavonoid derived from propolis originating from poplar.

3. The absorption enhancer according to claim 1, wherein the flavonoid is at least one selected from the group consisting of chrysin, galangin, and pinocembrin.

4. The absorption enhancer according to claim 1 , wherein the propolis derived from Baccharis duraunclifolia is a propolis ethanol extract.

5. The absorption enhancer according to any one of claims 1 to 4, which is a food or drink, a medicine, or a quasi-drug.

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