JP2023039414A - oral composition - Google Patents

Abstract

[Problem] To provide an oral composition having excellent absorption-promoting effect of cannabidiol. [Solution] An oral composition for promoting the absorption of cannabidiol, characterized by containing at least one functional ingredient selected from Astragalus membranaceus, Panax notoginseng, Bitter orange, polyamine, squalene, spore-forming lactic acid bacteria, tartaric acid, docosahexaenoic acid, eicosapentaenoic acid, astaxanthin, and krill. [Selected Figure] None

Description

The present invention relates to oral compositions containing cannabidiol, and in particular to oral compositions with enhanced absorption of cannabidiol.

Cannabidiol (CBD) is attracting attention as an ingredient expected to have a new pharmacological action. Cannabidiol is a type of cannabinoid contained in hemp, and for example, therapeutic agents for epileptic seizures, therapeutic compositions for tuberous sclerosis, and the like have been developed (Patent Documents 1 and 2).

Expecting such pharmacological effects of cannabidiol, various studies have been made. However, since cannabidiol is oil-soluble, it is difficult to be absorbed in the body, making it difficult to obtain sufficient pharmacological effects.

Japanese translation of PCT publication No. 2013-523708 Japanese Patent Publication No. 2017-537064

Accordingly, the present inventors conducted various studies with the object of enhancing the absorption-enhancing action of cannabidiol in the body.

As a result, the present inventors succeeded in developing an oral composition in which the absorption of cannabidiol is promoted by blending specific functional ingredients together with cannabidiol, thereby completing the present invention.

That is, the present invention is as follows.
<1> Characterized by containing at least one functional ingredient selected from Astragalus membranaceus, Panax ginseng, Citrus orange, Polyamine, Squalene, Spore-bearing lactic acid bacteria, Tartaric acid, Docosahexaenoic acid, Eicosapentaenoic acid, Astaxanthin, and Krill Oral composition for promoting the absorption of cannabidiol.
<2> An oral composition containing cannabidiol and at least one selected from polyamines, astaxanthin and krill.
<3> Containing cannabidiol and at least one functional ingredient selected from Astragalus membranaceus, Panax ginseng, Citrus orange, Polyamine, Squalene, Spore-bearing lactic acid bacteria, Tartaric acid, Docosahexaenoic acid, Eicosapentaenoic acid, Astaxanthin, and Krill An oral composition for promoting the absorption of cannabidiol, characterized by:
<4> At least selected from Astragalus membranaceus, Panax ginseng, Citrus aurantium, Polyamine, Squalene, Spore-bearing lactic acid bacteria, Tartaric acid, Docosahexaenoic acid, Eicosapentaenoic acid, Astaxanthin, Krill, Safflower oil, Olive oil, Medium-chain fatty acid oil, Flaxseed oil An oral composition for promoting the absorption of cannabidiol, characterized by containing two kinds of functional ingredients.
<5> At least selected from Astragalus membranaceus, Panax ginseng, Citrus aurantium, Polyamine, Squalene, Spore-bearing lactic acid bacteria, Tartaric acid, Docosahexaenoic acid, Eicosapentaenoic acid, Astaxanthin, Krill, Safflower oil, Olive oil, Medium-chain fatty acid oil, Flaxseed oil An oral composition for promoting the absorption of cannabidiol, comprising two functional ingredients and cannabidiol.
<6> An oral composition for promoting cannabidiol absorption, comprising at least two functional ingredients selected from safflower oil, olive oil, medium-chain fatty acid oil, and linseed oil.
<7> An oral composition for promoting the absorption of cannabidiol, comprising at least two functional ingredients selected from safflower oil, olive oil, medium-chain fatty acid oil and linseed oil, and cannabidiol.

According to the present invention, by containing a specific functional component together with cannabidiol, absorption of cannabidiol is enhanced, and various physiologically active effects of cannabidiol can be efficiently enjoyed.

The solid composition of the present invention will be described in detail below. In addition, the present invention is not limited to the embodiments shown below, and can be changed within the scope of those skilled in the art, such as other embodiments, additions, modifications, deletions, etc. is also included in the scope of the present invention as long as the functions and effects of the present invention are exhibited.

<Cannabidiol>
Cannabidiol is a type of cannabinoid known to be found in hemp. Cannabidiol is known to have different pharmacological effects from tetrahydrocannabinol, which is a kind of cannabinoid. In the present invention, cannabidiol can be extracted and purified from plants such as hemp and citrus peels, or synthesized. From the point of view, it is preferable to use a synthesized one.

The content of cannabidiol in the oral composition of the present invention is not particularly limited. It is particularly preferably 0.01% by mass or more from the viewpoint of easy and long-term oral intake. Moreover, 99.9 mass % or less is preferable and 99.5 mass % or less is more preferable. In addition, solid content in this specification is the amount which remove|excluding the water|moisture content from the composition.

In the present invention, the content of cannabidiol in the oral composition can be quantified, for example, by high performance liquid chromatography (HPLC). As the HPLC conditions, for example, using a column of Unison UK-C18HT (particle diameter 3 μm) φ4.6×150 mm manufactured by Intact Co., Ltd., using a water/acetonitrile mixture as the liquid medium of the mobile phase, the gradient conditions are Using Table 1 below, the analysis can be performed by setting the column temperature to 55° C. and the flow rate to 1.0 ml/min.

<Functional ingredients>
The oral composition of the present invention contains at least one functional ingredient selected from Astragalus membranaceus, ginseng, sour orange, rice, cod liver oil, spore-bearing lactic acid bacteria, tartaric acid, docosahexaenoic acid, eicosapentaenoic acid, haematococcus algae, and krill. characterized by containing By containing these functional ingredients, it becomes possible to promote absorption of cannabidiol into the body. In the present invention, from the viewpoint of increasing the absorbability of cannabidiol, the functional ingredient is preferably blended together with cannabidiol in the same composition. Moreover, in this invention, these functional ingredients can use 1 type(s) or 2 or more types. In particular, when safflower oil, olive oil, medium-chain fatty acid oil, and linseed oil are blended as functional ingredients, it is preferable to use two or more functional ingredients from the viewpoint of improving absorption promotion.

(Astragalus membranaceus)
Astragalus membranaceus (scientific name: Astragalus membranaceus) is a perennial plant belonging to the family Fabaceae. Astragalus membranaceus is known to contain flavonoids and saponins. As a part of Astragalus membranaceus, the whole may be used, or specific parts such as leaves, flowers, stems, seeds, buds, roots, underground stems (rhizome, corm, tuber, bulb) of the plant may be used. Although there is no particular limitation, aerial parts such as leaves, flowers, and stems are preferable because they are easily available, contain a large amount of saponin, and are excellent in promoting the absorption of cannabidiol.

In the present invention, the method for processing Astragalus membranaceus is not particularly limited, but since it is easy to use, contains a large amount of saponin, and is excellent in promoting the absorption of cannabidiol, it can be pulverized, squeezed, or extracted. are preferred, and extracts are particularly preferred. In the case of extracts, the extraction solvent is not particularly limited as long as it is usually used in oral compositions, and water, ethanol, or mixtures thereof are preferred, for example. A processed product of Astragalus membranaceus can be obtained, for example, by the method described later.

(Craned ginseng)
Panax notoginseng (scientific name: Panax notoginseng) is a plant belonging to the genus Panax notoginseng of the family Araliaceae, and is also known as Denshichi ginseng. Panax notoginseng is known to contain saponin. As the part of Sanchijijinjin, the whole may be used, or a specific part such as a plant leaf, flower, stem, seed, bud, root, underground stem (rhizome, corm, tuber, bulb) may be used. , There is no particular limitation, but roots, rhizomes, leaves, flowers, and stems are preferred because they are easily available, contain a lot of saponins, and have excellent cannabidiol absorption promoting effects. Leaves, flowers, Aerial parts such as stems are particularly preferred.

In the present invention, the method for treating Panax notoginseng is not particularly limited. Extracts are preferred, extracts are particularly preferred. In the case of extracts, the extraction solvent is not particularly limited as long as it is usually used in oral compositions, and water, ethanol, or mixtures thereof are preferred, for example. A processed product of Panax notoginseng can be obtained, for example, by the method described later.

(daidai)
Citrus aurantium (scientific name: Citrus Aurantium) is a green leaf plant belonging to the family Rutaceae. Citrus orange fruit is known to contain cyphnerine. As the part to be used of bitter orange, the whole may be used, or specific parts such as plant leaves, flowers, stems, seeds, buds, roots, underground stems (rhizome, corm, tuber, bulb) may be used. Although there is no particular limitation, fruits are preferable because they are easily available, because they contain a large amount of cyfnerine, and because they are excellent in promoting cannabidiol absorption.

In the present invention, there is no particular limitation on the method of processing Citrus aurantium. are preferred, and extracts are more preferred. In the case of extracts, the extraction solvent is not particularly limited as long as it is usually used in oral compositions, but water, ethanol, or mixtures thereof are preferred, for example. A processed product of sour orange can be obtained, for example, by the method described later.

(polyamine)
Polyamine is a general term for straight-chain aliphatic hydrocarbons in which three or more primary amino groups are bonded, and examples thereof include spermine, spermidine, and putrescine. Polyamines are known to be contained in plants such as milt, shellfish, legumes and rice. In the present invention, the origin of the polyamine is not particularly limited, but rice is preferred, and rice germ is particularly preferred, because it is easy to use, contains a large amount of polyamine, and has an excellent cannabidiol absorption promoting effect. Rice (rice; scientific name: Oryza sativa) is a plant belonging to the family Poaceae. Rice germ (rice germ) is known to contain polyamines.

In the present invention, the method of treating rice is not particularly limited. is preferred, an extract is more preferred, and an aqueous citric acid extract is particularly preferred. A processed rice product can be obtained, for example, by the method described later.

(squalene)
Squalene is an oily substance belonging to the triterpene family. Squalene is known to be contained in cod liver oil and olive oil. In the present invention, the origin of squalene is not particularly limited, but cod liver oil is preferred because it is easily available, contains a large amount of squalene, and has an excellent cannabidiol absorption promoting effect. Liver oil is the liquid contained in, or the fat extracted from, the livers of cod, shark, and ray. Shark liver oil is particularly preferred when liver oil is used as squalene in the present invention. Cod liver oil can be used either as it is or after extraction, but it is preferable to use refined cod liver oil or its extract because it contains a large amount of squalene.

(Spore-bearing lactic acid bacteria)
Spore-forming lactic acid bacteria are lactic acid bacteria that form spores, and are characterized by being resistant to dryness, heat and acid. Spore-bearing lactic acid bacteria include, for example, bacteria belonging to the genus Bacillus and Sporolactobacillus. In the present invention, the genus Bacillus is preferred, and Bacillus coagulans is particularly preferred, because it can be easily used and is excellent in promoting the absorption of cannabidiol. In the present invention, commercially available products that are usually available as food ingredients can be used.

(tartaric acid)
Tartaric acid is a hydroxy acid represented by (CH(OH)COOH) ₂ . In the present invention, commercially available products that are usually available as food ingredients can be used.

(docosahexaenoic acid)
Docosahexaenoic acid is a kind of ω-3 fatty acid, which is an unsaturated fatty acid, and is a general term for carboxylic acids having a 22-carbon chain containing six double bonds. Also called DHA. A type of essential fatty acid.

(eicosapentaenoic acid)
Eicosapentaenoic acid is a type of ω-3 fatty acid, which is an unsaturated fatty acid, and is a 20-carbon carboxylic acid with five cis double bonds. EPA, also called icosapentaenoic acid. A type of essential fatty acid.

(astaxanthin)
Astaxanthin is a red pigment substance. It is a kind of carotenoid and is classified as a xanthophyll. Astaxanthin is known to be contained in Haematococcus algae, crustaceans such as shrimp and crab, and salmon. Although the astaxanthin that can be used in the present invention is not particularly limited, astaxanthin derived from Haematococcus algae is preferable because it can be easily used and has an excellent cannabidiol absorption promoting effect. Haematococcus (Haematococcus pluvialis) is a kind of microalgae.

(Krill)
Krill is a crustacean that belongs to the order Krillidae of the order Molluscae of the subclass Eomalacia. Known krill include, for example, Antarctic krill (Euphausia superba), Euphausia pacifica (Isada, Euphausia pacifica), Euphausia crystallorophias, Thysanopoda obtusifrons, and Hibebuto krill . In the present invention, a krill extract is preferable, krill oil is more preferable, and krill oil is particularly preferable, because it can be easily used and has an excellent cannabidiol absorption promoting effect.

(safflower oil)
Safflower oil is a vegetable oil collected from the seeds of Safflower safflower belonging to the family Asteraceae, and is also called safflower oil or safflower oil.

(olive oil)
Olive oil is a vegetable oil obtained from fruits of the genus olive of the family Oleaceae.

(medium chain fatty acid oil)
A medium-chain fatty acid oil is a glyceride composed of saturated fatty acids having 8 to 12 carbon atoms. Fatty acids constituting the medium-chain fatty acid oil preferably have 8 to 10 carbon atoms. In addition, the medium-chain fatty acid oil used in the present invention is preferably one or more selected from medium-chain fatty acid triglycerides, diglycerides and monoglycerides, and medium-chain fatty acid triglycerides (Medium Chain Triglycerides: MCT) are essential. Especially preferred.

(linseed oil)
Flaxseed oil is a vegetable oil extracted from the seeds of the linseed family, the genus Flax, and is also called linseed oil, linseed oil, and flaxseed oil.

(Plant processing method)
Processed plant products include, for example, dry powder obtained by drying and pulverizing a plant (hereinafter also referred to as "dry pulverized powder"), shredded plant and its dried product, squeezed plant juice and Examples include, but are not limited to, dry powder thereof, extracts of plant bodies, and dry powder thereof. However, from the viewpoint of easiness of processing, storage, transportation, etc. and versatility of use form, it is preferable that the powder is finally in the form of powder. In the present specification, the term "powder" generally includes any of dry pulverized powder, dry powder of minced material, dry powder of squeezed juice, and dry powder of extract. Moreover, the processed plant product may be a fermented product of a plant or its dry powder. A fermented plant body is a product obtained by fermenting a plant body or its pulverized product, juice, extract, or shredded product.

A processed plant product can be processed by a conventionally well-known method. For example, as a method for drying and pulverizing a plant body, a method combining drying treatment and pulverizing treatment can be used for the plant body. Either the drying treatment or the pulverizing treatment may be performed first, but the drying treatment is preferably performed first. For the dry pulverization, this method may be combined with one or more treatments selected from treatments such as sterilization, if necessary. Further, the number of crushing treatments may be one or two or more treatments, but it is preferable to combine a coarse crushing treatment followed by a fine crushing treatment for finer crushing.

The drying treatment is not particularly limited, but includes, for example, drying so that the moisture content of the plant is 10% or less, preferably 8% or less. The drying treatment can be performed by any method known to those skilled in the art, such as hot air drying, high-pressure steam drying, electromagnetic wave drying, and freeze drying. Drying by heating can be carried out, for example, at 40° C. to 140° C., preferably 80° C. to 130° C., at a temperature and time at which the plant does not discolor.

The pulverization treatment is not particularly limited, but includes, for example, a treatment of pulverizing the plant by any method commonly used by those skilled in the art using a crusher, mill, blender, millstone or other crushing equipment or instrument. The pulverized plant body is sieved as necessary, and it is preferable to use, for example, a sieve that passes through 30 to 250 mesh as the plant powder. By setting the particle size to be 250 mesh or less, the plant powder can be easily handled during further processing, and by setting the particle size to be 30 mesh or more, the plant powder can be easily mixed with other materials. Uniform mixing is facilitated.

The method for fragmenting the plant body is not particularly limited, but methods commonly used by those skilled in the art to fragment the plant body, such as slicing, crushing, and shredding, can be used. As an example of comminution, it may be slurried. Slurrying is carried out by subjecting the plant body to a mixer, juicer, blender, masscolloider, or the like to form a mushy gruel (suspension of liquid and solid). When the shredded seeds are heated, water may be added to the liquid and boiled down, and the liquid may be used after removing coarse solids by means of sieving, filtration, or the like.

The method of squeezing the plant body is not particularly limited, but examples thereof include a method of squeezing the plant body or its fragmented material, a method of centrifuging or filtering the plant fragmented material, and the like. As an example of a specific squeezing method, the juice is squeezed by a mechanical crushing means such as a mixer or a juicer, and if necessary, a sieved liquid is obtained by removing coarse solids by means such as sieving or filtering. method.

The method of obtaining a plant extract (extract) is not particularly limited. A method of adding an extraction solvent and, if necessary, stirring and/or heating for extraction, and the like can be mentioned. Subsequent sieving, filtering or other means may remove crude solids to obtain an extract. For example, an extract obtained by adding water to shredded (grinded) soybeans, boiling it down, and then filtering the solids is known as soymilk. The extract may be concentrated if desired.

The method of fermenting a plant body can be performed by adding lactic acid bacteria, yeast, koji mold, natto bacteria, acetic acid bacteria, etc. to the plant body or its pulverized product, squeezed juice, extract or shredded product. These may be used alone or in combination of two or more. The lactic acid bacteria referred to herein may be bifidobacteria, or general lactic acid bacteria other than bifidobacteria.

The squeezed juice obtained by the above shredding process, the liquid extract obtained by the extraction process, the liquid material and slurry after fermentation are all dried by hot air drying, high-pressure steam drying, electromagnetic wave drying, freeze drying can be dry powdered by any method known in the art. At this time, an excipient such as dextrin may be added.

In the composition for oral use of the present embodiment, the processed plant product may be solid, liquid, syrup, paste, gel, jelly, cream, emulsion, spray, mousse, or lotion. It may be in a fluid state such as. Solids include powders, granules, granules, tablets, chewables, capsules, soft capsules, and the like.

The content of the functional ingredient in the oral composition of the present invention is not particularly limited. Especially preferably, it is 0.001 mass % or more from the point of being excellent in action. Moreover, it is preferably 99.9% by mass or less, more preferably 98% by mass or less, and particularly preferably 95% by mass or less. In addition, when multiple kinds of functional ingredients are contained, it is the total amount.

The content ratio of cannabidiol and functional ingredients in the oral composition of the present invention is not particularly limited. : 0.0001 or more, preferably 1:0.001 or more from the viewpoint of excellent cannabidiol absorption promoting action. Also, it is preferably 1:1000 or less, more preferably 1:200 or less, and particularly preferably 1:10 or less. In addition, when multiple kinds of functional ingredients are contained, it is the total amount.

<Other ingredients>
In addition to the above components, the oral composition of the present invention may optionally contain other components. Other ingredients include, for example, excipients, lubricants, dietary fibers such as water-soluble and insoluble dietary fibers, proteins, various vitamins and minerals, algae, microorganisms such as yeast, and the like. can. Furthermore, if necessary, sweeteners, acidulants, nutritional supplements, stabilizers, binders, brighteners, thickeners, coloring agents, diluents, emulsifiers, food additives, and seasonings that are usually used in the food field. fees, etc. The content of these other components can be appropriately selected according to the form of the composition of the present invention.

<Composition for promoting absorption>
The oral composition of the present invention can be used in various forms for the purpose of obtaining an absorption-enhancing effect of cannabidiol.

The composition for promoting absorption of the present invention contains at least one functional ingredient selected from Astragalus membranaceus, Panax ginseng, Citrus orange, polyamine, squalene, spore-bearing lactic acid bacteria, tartaric acid, docosahexaenoic acid, eicosapentaenoic acid, astaxanthin, and krill. It is characterized by containing Although these functional ingredients may be used as a composition separate from cannabidiol, they are preferably used as a composition containing cannabidiol from the viewpoint of the absorption promoting action of cannabidiol.

Further, the absorption-enhancing composition of the present invention is characterized by containing at least two functional ingredients selected from safflower oil, olive oil, medium-chain fatty acid oil, and linseed oil. Although these functional ingredients may be used as a composition separate from cannabidiol, they are preferably used as a composition containing cannabidiol from the viewpoint of the absorption promoting action of cannabidiol.

In the present invention, when the functional ingredient is a composition different from cannabidiol, the method of ingesting the composition containing the functional ingredient is not particularly limited. After is preferable, 2 hours before to 2 hours after is more preferable, 1 hour before to 1 hour after is particularly preferable, and simultaneous intake with cannabidiol is particularly preferable.

The oral composition of the present invention is not particularly limited as long as it is in a form suitable for oral use. From the viewpoint of ease of ingestion, the oral composition may be liquid, syrup, paste, gel, jelly, cream, It may be in a fluid form such as emulsion, spray, mousse or lotion. Solids include powders, granules, granules, tablets, chewables, capsules, soft capsules, and the like.

The daily usage amount of the oral composition of the present invention is not particularly limited, and can be appropriately set according to the mode of use, the details of use by the user, and the like. For example, the daily dose of the oral composition of the present invention is preferably 0.01 to 1000 mg/kg, more preferably 0.1 to 500 mg/kg, based on the body weight of the user, in terms of solid content. kg, and more preferably 1 to 100 mg/kg from the viewpoint of exhibiting the effects of the oral composition of the present invention.

Similarly, the amount of the oral composition of the present invention used once is not particularly limited. For example, the dosage of the oral composition of the present invention at one time is preferably 0.001 to 2000 mg/kg, more preferably 0.01 to 1000 mg/kg, based on the body weight of the user, in terms of solid content. kg, and more preferably 0.1 to 100 mg/kg from the viewpoint of exhibiting the effects of the oral composition of the present invention.

In addition, the daily usage amount of the oral composition of the present invention is not particularly limited. From the viewpoint of exhibiting the effect of , it is particularly preferably 0.01 to 5 g.

The amount of the oral composition of the present invention used at one time is not particularly limited. 0.0001 to 5 g is particularly preferable from the viewpoint of exhibiting.

In addition, the content of cannabidiol in the daily usage amount of the oral composition of the present invention is not particularly limited. From the viewpoint of exhibiting the effects of the composition, it is particularly preferably 0.0001 to 0.1 g.

The content of cannabidiol in the daily usage of the oral composition of the present invention is not particularly limited. From the viewpoint of exhibiting the effect of the oral composition of the present invention, it is particularly preferably 0.00001 to 0.1 g.

The packaging form of the oral composition of the present invention is not particularly limited, and can be appropriately selected according to the dosage form. Examples include blister packs such as PTP; strip packaging; heat sealing; aluminum pouches; film packaging; glass containers such as vials; and plastic containers such as ampoules.

EXAMPLES The present invention will be described below based on examples. However, the scope of the present invention is not limited to such examples.

Absorption promoting action of cannabidiol (1)
<Test substance>
The following were used as test substances.
・Cannabidiol: using a commercially available synthetic product ・Astragalus membranaceus: using a hydrous ethanol extract (containing saponin) from the aerial part of Astragalus membranaceus ・Ginseng: using a hydrous ethanol extract (containing saponin) from the aerial part of Astragalus membranaceus Citrus orange: using water-containing ethanol extract of orange peel pericarp (containing 6% or more cyphnerin) Polyamine: using citric acid aqueous extract of rice germ (containing 0.2% polyamine) Squalene: Purification of shark liver oil・Spore-bearing lactic acid bacteria: using commercially available Bacillus coagulans ・DHA: using purified fish oil (DHA 8.5% or more) ・EPA: using purified fish oil (EPA 1.2% or more) ・Astaxanthin : Haematococcus algae-derived astaxanthin Krill: Krill oil Safflower oil: Safflower seed-derived oil Olive oil: Olive fruit-derived oil Medium-chain fatty acid oil: MCT powder Used - linseed oil: using oil derived from linseed - oleic acid: using a commercially available standard reagent - deoxycholic acid: using a commercially available standard reagent A mixture of ginseng extracts (1:1), Example Purified fish oil containing DHA and EPA was used.

<Absorption promoting effect of cannabidiol>
1. Preparation of HBSS(+) HEPES Buffer (hereinafter also referred to as "buffer")
2.38 g of HEPES, 10×HBSS(−) 100 mL, NaHCO 350 mg, CaCl ₂ 140 mg, MgCl _{2.6H 2} O 100 mg, and MgSO _{4.7H 2} O 100 mg were dissolved in 850 mL of ultrapure _water and adjusted to pH 7 with 1 M NaOH. After adjusting to .4, a buffer was prepared with a total volume of 1 L.

2. Cell Culture and Addition of Test Substances (1) Human colon cancer-derived cells (Caco-2) were cultured in a 37° C., 5% CO ₂ incubator using a 75 cm ² flask. The medium used was 1% NEAA (MEM Non-Essential Amino Acids Solution)-10% FBS-DMEM.
(2) 600 μL of medium was added to a 24-well plate and the insert wells were transferred.
(3) 100 μL of cells suspended by trypsinization were seeded from a 75 cm ² flask to insert wells at a cell density of 4.0×10 ⁴ cells/well.
(4) The cells were cultured in a 37°C, 5% CO ₂ incubator, and the medium was changed every 2-3 days. The medium was exchanged with 1600 μL of 1% NEAA-10% FBS-DMEM for the outer side of the insert well (well on the basement membrane side) and 350 μL of 1% NEAA-10% FBS-DMEM on the inner side of the insert well (well on the luminal side). The electrical resistance value was measured with a Millicell ERS-2, cultured until 1500Ω or more, and used for the test.
(5) The insert wells were washed twice with buffer, transferred to a 24-well plate, and 350 μL of buffer was added to the lumen side wells and 1600 μL to the basement membrane side wells.
(6) cultured in a _CO2 incubator for 30 minutes to acclimatize the cells to the buffer;
(7) After removing 175 µL of the buffer inside the insert wells, 175 µL of the test substance solution was added and shaken in an incubator for 2 hours.
Cannabidiol was dissolved in a surfactant (PEG40-hydrogenated castor oil) and functional ingredients were dissolved in DMSO or a buffer containing 0.5% DMSO. After addition to cells, cannabidiol is 500 μg / mL (surfactant (PEG40-hydrogenated castor oil): 0.5%) and functional ingredients are 2.5 μg / mL (DMSO: 0.125%) prepared and added to the cells.
(8) After shaking for 2 hours, the entire amount of the sample in the luminal well was collected in a 1.5 mL tube.

3. Measurement of cannabidiol concentration using dinitrophenol (1) 1.5 mL of the luminal well sample collected in 2 (8) above, a solution containing 500 μg/mL of cannabidiol before addition to the cells, and 50 μL of the standard curve sample It was transferred to a tube, and 250 μL of 4 M sodium hydroxide solution was added. Furthermore, 200 μL of 0.1 (W/V) % dinitrophenol solution was added and mixed. A calibration curve was obtained by serially diluting cannabidiol dissolved in ethanol.
(2) Heated at 100° C. for 50 minutes, mixed by vortexing, and centrifuged (room temperature, 10 minutes, 20,000 g).
(3) The supernatant after centrifugation was transferred to a 96-well assay plate and the absorbance was measured (500 nm, 650 nm (turbidity)).
(4) Using the value obtained by subtracting the absorbance (turbidity) at 650 nm from the absorbance at 500 nm, the cannabidiol concentration in each sample was evaluated from the calibration curve. (Measurement method reference: T Aman et al. Spectrophotometric Determination of Cannabidiol. ANALYTICAL LETTERS (1993) 26(10))
The reduction in cannabidiol (μg) was calculated from the concentration of cannabidiol in the solution containing 500 μg/mL of cannabidiol before addition to the cells and the cannabidiol concentration in the luminal well sample. A relative value was calculated when the amount of decrease in Comparative Example 1 containing no functional ingredient (only cannabidiol) was set to 1. The results are shown in Tables 2 and 3.

Caco-2 cells are generally used as intestinal model cells to evaluate the intestinal absorbability of test substances. Caco-2 cells are differentiated into a monolayer in the insert well, and when the test substance is added to the culture supernatant on the luminal side, the test substance is passively or actively taken up into the cells, and part of it is metabolized and degraded. After receiving the test substance, it is secreted into the permeate on the basement membrane side, so the intestinal absorbability of the test substance can be evaluated by measuring the amount of the test substance contained in the permeate. In this evaluation system, the decrease in the test substance in the culture supernatant and the increase in the test substance in the permeate are correlated (Reference: Food Functionality Evaluation Manual Collection III "Substance Permeation Experiment Using Caco-2 Cell Layer Law” Makoto Shimizu et al.). From this, it is considered that the decreased amount of the test substance in the culture supernatant reflects the amount of uptake into the cells.
When micellar cannabidiol was added to Caco-2 cells differentiated into monolayer cells, the amount of cannabidiol in the culture supernatant decreased. Cannabidiol was not detected in the permeate, but it was confirmed that cannabidiol did not adhere to the cell surface and that cannabidiol was not decomposed in the medium. Presumably, it is taken up into cells. Therefore, the decreased amount of cannabidiol in the culture supernatant can be evaluated as the intracellular uptake of cannabidiol (absorbed amount of cannabidiol).
It was found that Examples 1 to 13, in which the functional ingredient was added together with cannabidiol, absorbed 1.2 times more cannabidiol than Comparative Example 1, in which no functional ingredient was added. In addition, it was found that the absorption of cannabidiol was enhanced compared to oleic acid and deoxycholic acid, which are known to enhance the absorption of cannabidiol.
Therefore, it was suggested that the oral composition of the present invention promotes absorption of cannabidiol in intestinal cells by containing specific functional ingredients.

Absorption promoting action of cannabidiol (2)
<Test substance>
The following were used as test substances.
・Cannabidiol: using a commercially available synthetic product ・Squalene: using purified shark liver oil ・Piperine: using piperine derived from black pepper

After acclimatization for 5 days or more, male SD rats were grouped into 3 groups. After grouping, the test substance was orally administered by gavage. Two hours after administration, blood was collected from the jugular vein using a syringe containing an anticoagulant (Na heparin), and centrifuged to collect plasma. After deproteinization as a pretreatment, cannabidiol concentration in plasma was analyzed by high performance liquid chromatography (HPLC).

(Analysis conditions)
Column: Unison UK-C18HT (particle size 3 μm) manufactured by Intact Co., Ltd. φ4.6×150 mm
Mobile phase: water / acetonitrile mixture Gradient conditions: Table 4
Column temperature: 55°C
Flow rate: 1.0ml/min

Table 5 shows the dose of the test substance and the amount of cannabidiol in the plasma 2 hours after administration of the test substance.

As is clear from Table 5, in Example 14 using cannabidiol and squalene, the amount of cannabidiol in plasma was significantly increased compared to Comparative Example 4 using cannabidiol alone, and squalene was released into the body. was found to enhance the absorption of cannabidiol in This result is also supported by the fact that Example 4 showed a higher absorption promoting effect than Comparative Example 1 in "Absorption promoting action of cannabidiol (1)", and the composition of the present invention was combined with cannabidiol. It was suggested that the use of specific functional ingredients would enhance the absorption of cannabidiol into the body. It was also found that the absorption of cannabidiol was enhanced in the composition of the present invention as compared with the case where piperine and cannabidiol, which are known to enhance the absorption of cannabidiol, were used in combination (Comparative Example 5). rice field.

<Production Example 1>
Tablets (250 mg per tablet) were produced according to the composition shown in Table 6 below. The compounding amounts shown in the table represent % by mass. Since the oral composition obtained in the following production example has a high cannabidiol absorption-enhancing effect, the excellent effects of cannabidiol can be obtained by taking 2 capsules once a day.

<Production Example 2>
Tablets (200 mg per tablet) were produced according to the composition shown in Table 7 below. The compounding amounts shown in the table represent % by mass. Since the oral composition obtained in the Production Example below has a high cannabidiol absorption-enhancing effect, the excellent effects of cannabidiol can be obtained by taking 3 tablets once a day.

<Production Example 3>
A soft capsule content liquid was produced according to the composition shown in Table 8 below. The compounding amounts shown in the table represent % by mass. The resulting liquid content was wrapped with a gelatin film to produce soft capsules (300 mg each). Since the oral composition obtained in the Production Example below has a high cannabidiol absorption-enhancing effect, the excellent effects of cannabidiol can be enjoyed by taking one tablet per dose once a day.

<Production Example 4>
An oral oil was prepared according to the composition given in Table 9 below. The compounding amounts shown in the table represent % by mass. Since the oral composition obtained in the Production Example below has a high cannabidiol absorption-enhancing effect, the excellent effects of cannabidiol can be obtained by taking 0.1 mL of the composition once a day.

INDUSTRIAL APPLICABILITY The oral composition of the present invention can provide an oral composition having an excellent cannabidiol absorption-enhancing effect by containing a specific functional ingredient, and thus has a high possibility of industrial application. be.

Claims (4)

Cannabidiol characterized by containing at least one functional ingredient selected from Astragalus membranaceus, Panax ginseng, Citrus aurantium, Polyamine, Squalene, Spore-bearing lactic acid bacteria, Tartaric acid, Docosahexaenoic acid, Eicosapentaenoic acid, Astaxanthin, and Krill oral composition for promoting the absorption of An oral composition containing cannabidiol and at least one selected from polyamines, astaxanthin and krill. It contains at least one functional ingredient selected from Astragalus membranaceus, Panax ginseng, Citrus orange, polyamine, squalene, spore-bearing lactic acid bacteria, tartaric acid, docosahexaenoic acid, eicosapentaenoic acid, astaxanthin, and krill, and cannabidiol. An oral composition for enhancing the absorption of cannabidiol characterized by: An oral composition for promoting cannabidiol absorption, comprising at least two functional ingredients selected from safflower oil, olive oil, medium-chain fatty acid oil and linseed oil.