Composition for improving quality of sleep

Abstract

To provide a composition for improving quality of sleep that demonstrates excellent efficacy in improving sleep quality.SOLUTION: A composition for improving quality of sleep characterized by comprising cannabidiol and at least one component selected from the group consisting of (a) a processed plant material, (b) an amino acid, and (c) a functional component.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for improving sleep quality that contains cannabidiol and specific ingredients. [Background technology]

[0002] Cannabidiol (CBD) is attracting attention as a component expected to have new pharmacological effects. Cannabidiol (CBD) is a type of cannabinoid found in hemp, and has been developed as a therapeutic agent for epilepsy and a composition for treating tuberous sclerosis (Patent Document 1, Patent Document 2). Its use as an oral composition and topical agent has also been developed, but has not been fully explored. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Special Publication No. 2013-523708 [Patent Document 2] Special Publication No. 2017-537064 Summary of the Invention [Problem to be solved by the invention]

[0004] Therefore, the present inventors have conducted various studies with the objective of providing a composition that enhances the effects of cannabidiol. [Means for solving the problem]

[0005] As a result, the inventors discovered that a significant effect of improving sleep quality can be achieved by combining cannabidiol with a specific component, and thus completed the present invention.

[0006] That is, the present invention is as follows. <1> A composition for improving sleep quality, comprising cannabidiol and at least one component selected from the following (a) to (c): (a) Plant treatments (b) amino acids (c) Functional ingredients <2> (a) The plant treatment product is at least one selected from the group consisting of valerian, daylily, passionflower, and chamomile. <1> A composition for improving sleep quality described in claim 1. <3> (b) The amino acid is at least one selected from tryptophan, glycine, valine, leucine, isoleucine, lysine, methionine, phenylalanine, threonine, histidine, theanine, and γ-aminobutyric acid. <1> A composition for improving sleep quality described in claim 1. <4> (c) The functional ingredient is at least one selected from sesamin, α-glycerylphosphorylcholine, collagen, ceramide, hyaluronic acid, elastin, and vitamin C. <1> A composition for improving sleep quality described in claim 1. <5> The improvement in sleep quality is at least one selected from the group consisting of reduction of sleepiness upon waking, promotion of sleep onset, increase in sleep time, reduction in dreaminess, reduction of fatigue upon waking, reduction of time spent awake during the night, reduction of daytime sleepiness, improvement of sleep rhythm, improvement of sleep depth, and improvement of sleep satisfaction. <1> A composition for improving sleep quality described in claim 1. [Effects of the Invention]

[0007] According to the present invention, by containing a specific component together with cannabidiol, the inhibitory effect on calcium uptake into nerve cells is enhanced, and therefore an excellent composition for improving sleep quality can be obtained. DETAILED DESCRIPTION OF THE INVENTION

[0008] The sleep quality improving composition of the present invention will be described in detail below. Note that the present invention is not limited to the following embodiments, and other modifications, additions, corrections, deletions, and other changes can be made within the scope of those skilled in the art. Any embodiment is within the scope of the present invention as long as it exhibits the functions and effects of the present invention.

[0009] <Cannabidiol> The sleep quality improving composition of the present invention is characterized by containing cannabidiol. Cannabidiol is a type of cannabinoid known to be contained in hemp. Cannabidiol is known to have a different pharmacological effect from tetrahydrocannabinol, which is also a type of cannabinoid. In the present invention, cannabidiol extracted and purified from plants such as hemp or citrus peel, or synthesized cannabidiol can be used. However, from the viewpoints of safety and enhanced sleep quality improving effect, it is preferable to use cannabidiol extracted and purified from natural products.

[0010] The content of cannabidiol in the sleep quality improving composition of the present invention is not particularly limited, and is, for example, preferably 0.0001% by mass or more, more preferably 0.0005% by mass or more, and particularly preferably 0.001% by mass or more in terms of its excellent effect of improving sleep quality. Also, it is preferably 80% by mass or less, more preferably 70% by mass or less, and particularly preferably 50% by mass or less in terms of its excellent effect of improving sleep quality.

[0011] In the present invention, the cannabidiol content in the composition for improving sleep quality can be quantified, for example, by high performance liquid chromatography (HPLC). The HPLC conditions can be, for example, using a Unison UK-C18HT (particle size 3 μm) φ4.6 × 150 mm column manufactured by Intact Corporation, a water / acetonitrile mixture as the mobile phase, the gradient conditions shown in Table A below, a column temperature of 55°C, and a flow rate of 1.0 ml / min.

[0012] [Table A]

[0013] <Specific ingredients> The composition for improving sleep quality of the present invention is characterized by containing cannabidiol and at least one component selected from (a) processed plant products, (b) amino acids, and (c) functional components. (a) to (c) are described in detail below.

[0014] (a) Plant treatments One type of specific component used together with cannabidiol in the present invention is a processed plant product, which is obtained by processing a plant body by any of processes such as drying, crushing, extraction, filtration, squeezing, slurrying, heating, fermentation, etc.

[0015] (Valeriana officinalis) Valeriana officinalis L. is a perennial plant of the Valeriaceae family, also known as valerian, kasso (valerian root), or kisso (valerian grass). Valeriana officinalis contains valeric acid, terpenes, alkaloids, and the rhizomes and roots containing these components are called valerian roots. Valeriana officinalis may be used in its entirety, or specific parts of the plant, such as leaves, flowers, roots, stems, rhizomes (rhizomes, corms, tubers, bulbs), seeds, or buds, may be used without any particular limitation. However, roots or rhizomes are particularly preferred due to their ease of use and their excellent effect in improving sleep quality.

[0016] In the present invention, the method for processing valerian is not particularly limited, but a crushed product, a squeezed product, or an extract is preferred, and an extract is particularly preferred, from the viewpoints of ease of use and superior effects of improving sleep quality. Processed valerian can be obtained, for example, by the method described below.

[0017] (Daylily) Hemerocallis fulva var. sempervirens is a perennial plant of the genus Forget-me-not, subfamily Hemerocallis, family Xanthomaceae, and also known as tokiwa-kanzo, evergreen daylily, kwansou, kwansou, gansou, gansho, kanzobana, and nemurigusa. The whole plant may be used, or specific parts of the plant, such as leaves, flowers, roots, stems, rhizomes (rhizomes, corms, tubers, bulbs), seeds, and buds, may also be used, without any particular limitation. However, leaves and / or stems are particularly preferred because of their ease of use and their excellent effect of improving sleep quality.

[0018] In the present invention, the method for processing daylily is not particularly limited, but a crushed product, a squeezed product, or an extract is preferred, with a squeezed product and an extract being particularly preferred, because they are easy to use and have an excellent effect of improving the quality of sleep. Processed daylily products can be obtained, for example, by the methods described below.

[0019] (Passion Flower) Passiflora incarnata is a perennial plant of the Passifloraceae family, also known as passion flower. Passiflora incarnata may be used in its entirety, or specific parts such as leaves, flowers, roots, stems, rhizomes (corms, tubers, bulbs), seeds, and buds may be used. While there are no particular limitations on the parts, the above-ground parts (flowers, leaves, and stems) are particularly preferred for their ease of use and their superior effect in improving sleep quality.

[0020] In the present invention, the method for processing passionflower is not particularly limited, but a crushed product, a squeezed product, or an extract is preferred, and a squeezed product or an extract is particularly preferred, in terms of ease of use and excellent effects of improving sleep quality. A processed passionflower can be obtained, for example, by the method described below.

[0021] (chamomile) Chamomile (Matricaria recutita L.) is an annual plant of the Asteraceae family, also known as chamomile, chamomile, German chamomile, German chamomile, and German chamomile. The entire chamomile plant may be used, or specific parts of the plant, such as leaves, flowers, roots, stems, rhizomes (rhizomes, corms, tubers, bulbs), seeds, and buds, may also be used. While there are no particular limitations, the aboveground parts (flowers, leaves, and stems) are preferred, with flowers being particularly preferred, due to their ease of use and superior effects in improving sleep quality.

[0022] In the present invention, the method for processing chamomile is not particularly limited, but a crushed product, squeezed product, or extract is preferred, and a squeezed product or extract is particularly preferred, from the viewpoint of ease of use and superior effects of improving sleep quality. Processed chamomile products can be obtained, for example, by the methods described below.

[0023] (Plant processing method) Examples of processed plant products include, but are not limited to, dried powders obtained by drying and pulverizing a plant body (hereinafter also referred to as "dried and pulverized powder"), shredded plant body products and their dried products, squeezed plant body juice and its dried powder, and plant body extracts and its dried powder. However, from the viewpoints of ease of processing, storage, transportation, etc., and versatility of use, it is preferable that the final product be in powder form. In this specification, the term "powder" generally includes any of dried and pulverized plant powder, dried shredded product powder, dried juice powder, and dried extract powder. The processed plant product may also be a fermented plant body product or its dried powder. A fermented plant body product is a fermented plant body or its pulverized product, squeezed juice, extract, or shredded product.

[0024] Treated plant products can be processed by conventionally known methods. For example, a method of drying and pulverizing a plant body into powder can be a method of combining a drying treatment and a pulverization treatment on the plant body. Either the drying treatment or the pulverization treatment can be performed first, but it is preferable to perform the drying treatment first. This method of drying and pulverization into powder can be further combined with one or more treatments selected from treatments such as sterilization, as necessary. Furthermore, the pulverization treatment can be performed once or twice or more times, but it is preferable to combine a coarse pulverization treatment with a fine pulverization treatment for more fine pulverization.

[0025] The drying treatment is not particularly limited, but examples include a treatment in which the plant body is dried to a moisture content of 10% or less, preferably 8% or less. Drying treatment can be carried out by any method known to those skilled in the art, such as hot air drying, high-pressure steam drying, electromagnetic wave drying, freeze-drying, etc. Drying by heating can be carried out at a temperature of, for example, 40°C to 140°C, preferably 80°C to 130°C, for a time period that does not cause discoloration of the plant body.

[0026] The grinding process is not particularly limited, but examples include grinding the plant body by any method commonly used by those skilled in the art using grinding equipment or tools such as a crusher, mill, blender, or stone mill. The ground plant body is sieved as needed, and it is preferable to use plant body powder that passes through a 30 to 250 mesh sieve, for example. By using a particle size that passes through a 250 mesh or smaller, the plant body powder becomes easier to handle during further processing, and by using a particle size that passes through a 30 mesh or larger, the plant body powder can be easily mixed uniformly with other materials.

[0027] The method for shredding the plant body is not particularly limited, and methods commonly used by those skilled in the art for shredding plants, such as slicing, crushing, and chopping, can be used. One example of shredding is slurrying. Slurrying can be performed by subjecting the plant body to a mixer, juicer, blender, mass colloider, or the like to create a thick gruel-like substance (a suspension of liquid and solids). When shredded seeds are heated, the liquid can be boiled down with water, and the coarse solids can be removed by sieving, filtration, or the like, and the liquid can be used.

[0028] The method for extracting juice from a plant body is not particularly limited, and examples thereof include a method of squeezing the plant body or a fragment thereof, a method of centrifuging or filtering a fragment of the plant body, etc. Specific examples of the juicing method include a method of extracting juice by mechanical crushing means such as a mixer or a juicer, and then removing coarse solids by means of sieving, filtration, etc., as necessary, to obtain a squeezed juice.

[0029] The method for obtaining an extract from a plant is not particularly limited, but examples include a method in which an extraction solvent commonly used by those skilled in the art, such as ethanol, water, or aqueous ethanol, is added to the plant or its shredded or dried product, and the mixture is stirred and / or heated as necessary to obtain an extract. The extract may then be obtained by removing coarse solids by sieving, filtration, or other means. For example, an extract obtained by adding water to shredded soybeans (ground soybeans), boiling the mixture, and then filtering the solids is known as soy milk. The extract may also be concentrated as needed.

[0030] Fermentation of a plant can be carried out by adding lactic acid bacteria, yeast, koji mold, natto bacteria, acetic acid bacteria, etc. to the plant or its pulverized product, juice, extract, or shredded product. These may be used alone or in combination of two or more.

[0031] The juice obtained by the above-mentioned shredding process, the liquid extract obtained by the extraction process, and the liquid or slurry after fermentation can all be dried and powdered by any method known to those skilled in the art, such as hot air drying, high-pressure steam drying, electromagnetic wave drying, freeze-drying, etc. In this case, an excipient such as dextrin may be added.

[0032] In the oral composition of this embodiment, the plant treatment product may be in a solid form or a fluid form such as a liquid, syrup, paste, gel, jelly, cream, emulsion, spray, mousse, lotion, etc. Examples of solid forms include powder, granules, tablets, chewable tablets, capsules, and soft capsules.

[0033] (b) amino acids One of the specific components used in conjunction with cannabidiol in the present invention is amino acid. This is a general term for organic compounds having both amino and carboxyl functional groups, and depending on the position of the amino group, there are α-amino acids, β-amino acids, γ-amino acids, and δ-amino acids. There are no particular limitations on the amino acids that can be used in the present invention, but α-amino acids, β-amino acids, and γ-amino acids are preferred, with α-amino acids and γ-amino acids being particularly preferred.

[0034] (tryptophan) Tryptophan is an aromatic amino acid with an indole ring in its side chain. It is an essential amino acid in humans and has the systematic name 2-amino-3-(indolyl)propionic acid, abbreviated as Trp or W. Tryptophan exists as L-, D-, and DL-isomers, and any of these can be used. However, the L- and DL-isomers are preferred, with the L-isomer being more preferred, due to its superior effect in improving sleep quality.

[0035] Tryptophan can be used not only in the free form but also in the form of a salt. Examples of salts include acid addition salts and salts with bases, and it is preferable to select a pharmacologically acceptable salt. Specific examples of tryptophan salts include salts with inorganic bases, organic bases, inorganic acids, and organic acids. In the present invention, the free form or organic acid salts are preferred, the free form or hydrochloride salts are more preferred, and the free form is particularly preferred, from the viewpoint of excellent sleep quality improvement effects. In the present invention, commercially available products that are usually available as food ingredients can be used.

[0036] (glycine) Glycine is an amino acid, an aminoacetic acid, which has the simplest form of the amino acids that make up proteins. It is also known as glycochol and is abbreviated as Gly or G.

[0037] Glycine can be used not only in the free form but also in the form of a salt. Examples of salts include acid addition salts and salts with bases, and it is preferable to select a pharmacologically acceptable salt. Specific examples of glycine salts include salts with inorganic bases, organic bases, inorganic acids, and organic acids. In the present invention, the free form or organic acid salts are preferred, the free form or hydrochloride salts are more preferred, and the free form is particularly preferred, from the viewpoint of excellent sleep quality improvement effects. In the present invention, commercially available products that are usually available as food ingredients can be used.

[0038] (Ballin) Valine is a branched-chain amino acid. It is one of the essential amino acids for humans and is also known as 2-aminoisovaleric acid, abbreviated as Val or V. Valine exists as an isomer, such as L-, D-, or DL-isomer, and any of these can be used. However, the L- and DL-isomers are preferred, with the L-isomer being more preferred, due to its superior effect in improving sleep quality.

[0039] Valine can be used not only in the free form but also in the form of a salt. Examples of salts include acid addition salts and salts with bases, and it is preferable to select a pharmacologically acceptable salt. Specific examples of valine salts include salts with inorganic bases, organic bases, inorganic acids, and organic acids. In the present invention, the free form or organic acid salts are preferred, the free form or hydrochloride salts are more preferred, and the free form is particularly preferred, because of their excellent effect of improving sleep quality. In the present invention, commercially available products that are usually available as food ingredients can be used.

[0040] (Leucine) Leucine is a type of amino acid, a branched-chain amino acid that is essential for humans, and is abbreviated as Leu or L. Leucine exists in the form of isomers, such as L-, D-, and DL-isomers, and any of these can be used. However, the L- and DL-isomers are preferred, with the L-isomer being more preferred, due to their superior effect in improving sleep quality.

[0041] Leucine can be used not only in the free form but also in the form of a salt. Examples of salts include acid addition salts and salts with bases, and it is preferable to select a pharmacologically acceptable salt. Specific examples of leucine salts include salts with inorganic bases, organic bases, inorganic acids, and organic acids. In the present invention, the free form or organic acid salts are preferred, the free form or hydrochloride salts are more preferred, and the free form is particularly preferred, from the viewpoint of excellent sleep quality improvement effects. In the present invention, commercially available products that are usually available as food ingredients can be used.

[0042] (Isoleucine) Isoleucine is a branched-chain amino acid. It is one of the essential amino acids for humans and is also known as 2-amino-3-methylpentanoic acid (2-amino-3-methylvaleric acid), abbreviated as Ile or I. Isoleucine exists as an L-, D-, or DL-isomer, and any of these can be used. However, the L- and DL-isomers are preferred, with the L-isomer being more preferred, due to its superior effect in improving sleep quality.

[0043] Isoleucine can be used not only in the free form but also in the form of a salt. Examples of salts include acid addition salts and salts with bases, and it is preferable to select a pharmacologically acceptable salt. Specific examples of salts of isoleucine include salts with inorganic bases, organic bases, inorganic acids, and organic acids. In the present invention, the free form or organic acid salts are preferred, the free form or hydrochloride salts are more preferred, and the free form is particularly preferred, from the viewpoint of excellent sleep quality improvement effects. In the present invention, commercially available products that are usually available as food ingredients can be used.

[0044] (lysine) Lysine is a basic amino acid. It is one of the essential amino acids for humans and is also called lysine, abbreviated as Lys or K. Lysine exists as an isomer, such as L-isomer, D-isomer, or DL-isomer, and any of these can be used. However, the L-isomer and DL-isomer are preferred, with the L-isomer being more preferred, due to their superior effect in improving sleep quality.

[0045] Lysine can be used not only in the free form but also in the form of a salt. Examples of salts include acid addition salts and salts with bases, and it is preferable to select a pharmacologically acceptable salt. Specific examples of lysine salts include salts with inorganic bases, organic bases, inorganic acids, and organic acids. In the present invention, the free form or organic acid salts are preferred, the free form or hydrochloride salts are more preferred, and the free form is particularly preferred, because of their excellent effect of improving sleep quality. In the present invention, commercially available products that are usually available as food ingredients can be used.

[0046] (methionine) Methionine is a hydrophobic amino acid containing sulfur in the side chain. It is an essential amino acid in humans and is abbreviated as Met or M. Methionine exists as L-, D-, and DL-isomers, and any of these can be used. However, the L- and DL-isomers are preferred, with the L-isomer being more preferred, due to its superior effect in improving sleep quality.

[0047] Methionine can be used not only in the free form but also in the form of a salt. Examples of salts include acid addition salts and salts with bases, and it is preferable to select a pharmacologically acceptable salt. Specific examples of methionine salts include salts with inorganic bases, organic bases, inorganic acids, and organic acids. In the present invention, the free form or organic acid salts are preferred, the free form or hydrochloride salts are more preferred, and the free form is particularly preferred, because of their excellent effect of improving sleep quality. In the present invention, commercially available products that are usually available as food ingredients can be used.

[0048] (phenylalanine) Phenylanine is an aromatic amino acid with a benzyl group in the side chain. It is an essential amino acid in humans and is abbreviated as Phe or F. Phenylanine exists as L-, D-, and DL-isomers, and any of these can be used. However, the L- and DL-isomers are preferred, with the L-isomer being more preferred, due to its superior effect in improving sleep quality.

[0049] Phenylanine can be used not only in the free form but also in the form of a salt. Examples of salts include acid addition salts and salts with bases, and it is preferable to select a pharmacologically acceptable salt. Specific examples of phenylalanine salts include salts with inorganic bases, organic bases, inorganic acids, and organic acids. In the present invention, the free form or organic acid salts are preferred, the free form or hydrochloride salts are more preferred, and the free form is particularly preferred, from the viewpoint of excellent sleep quality improvement effects. In the present invention, commercially available products that are usually available as food ingredients can be used.

[0050] (Threonine) Threonine is a type of amino acid that has a hydroxyethyl group in its side chain and is also called threonine. It is one of the essential amino acids in humans and is abbreviated as Thr or T. Threonine has two optically active centers, and therefore exists as four isomers: L-threonine, D-threonine, L-allothreonine, and D-allothreonine. In the present invention, L-threonine, D-threonine, or a mixture thereof is preferred, and L-threonine is more preferred because of its excellent effect of improving sleep quality.

[0051] Threonine can be used not only in the free form but also in the form of a salt. Examples of salts include acid addition salts and salts with bases, and it is preferable to select a pharmacologically acceptable salt. Specific examples of threonine salts include salts with inorganic bases, organic bases, inorganic acids, and organic acids. In the present invention, the free form or organic acid salts are preferred, the free form or hydrochloride salts are more preferred, and the free form is particularly preferred, because of their excellent effect of improving sleep quality. In the present invention, commercially available products that are usually available as food ingredients can be used.

[0052] (histidine) Histidine is an aromatic amino acid with a heteroaromatic ring in the side chain. It is an essential amino acid in humans and is abbreviated as His or H. Histidine exists as L-, D-, and DL-isomers, and any of these can be used. However, the L- and DL-isomers are preferred, with the L-isomer being more preferred, due to their superior effect in improving sleep quality.

[0053] Histidine can be used not only in the free form but also in the form of a salt. Examples of salts include acid addition salts and salts with bases, and it is preferable to select a pharmacologically acceptable salt. Specific examples of histidine salts include salts with inorganic bases, organic bases, inorganic acids, and organic acids. In the present invention, histidine is preferably in the free form or an organic acid salt, more preferably in the free form or a hydrochloride salt, and particularly preferably in the free form, because of its excellent effect of improving sleep quality. In the present invention, commercially available products that are usually available as food ingredients can be used.

[0054] (Theanine) Theanine (L-theanine) is an amino acid found in tea and is also known as γ-glutamylethylamide or γ-(ethylamide) L-glutamic acid. In the present invention, commercially available products that are commonly available as food ingredients can be used.

[0055] (γ-aminobutyric acid) γ-aminobutyric acid (GABA), also known as gamma-aminobutyric acid (GABA), is an amino acid found widely in the animal and plant kingdoms and is an inhibitory neurotransmitter present in the brain and spinal cord of mammals. GABA can be derived from synthetic sources, plant-derived sources such as tea, young barley leaves, and germinated brown rice, or from fermentation products using microorganisms such as lactic acid bacteria. However, synthetic sources and fermentation products using microorganisms such as lactic acid bacteria are preferred due to their ease of use and superior sleep quality improvement effects.

[0056] (c) Functional ingredients One of the specific ingredients used in the present invention together with cannabidiol is an anti-fatigue ingredient.The functional ingredient is an ingredient that can enhance the effect of improving sleep quality when used in combination with cannabidiol.The functional ingredients that can be used in the present invention include, for example, sesamin, α-glycerylphosphorylcholine, collagen, ceramide, hyaluronic acid, elastin, and vitamin C.

[0057] (sesamin) Sesamin is a component of sesame lignans. The sesamin used in the present invention includes sesamin and its analogs, such as episesamin and dioxabicyclo[3.3.0]octane derivatives. Specific examples of sesamins include sesamin, sesaminol, episesaminol, and sesamolin. Commercially available products commonly available as food ingredients can be used in the present invention.

[0058] (α-glycerylphosphorylcholine) α-Glycerylphosphorylcholine (α-GPC), a choline derivative also known as sn-glycero(3)phosphocholine or water-soluble choline, is a precursor of acetylcholine, which acts on the parasympathetic nervous system. α-GPC is naturally occurring and is found in milk and the brain. In the present invention, commercially available products commonly available as food ingredients can be used.

[0059] (collagen) Collagen is a type of protein that mainly constitutes the dermis, ligaments, tendons, bones, cartilage, etc. of vertebrates, and is the main component of the extracellular matrix of multicellular animals.

[0060] The collagen used in the present invention may be animal-derived collagen, fish-derived collagen, synthetic collagen, gelatin, collagen protein, collagen peptides obtained by decomposing collagen protein, or atelocollagen obtained by treating collagen molecules with protease to remove the telopeptide portion. The average molecular weight (weight-average molecular weight) of the collagen of the present invention is not particularly limited, but for example, the lower limit of the average molecular weight is preferably 100 or more, more preferably 300 or more, and particularly preferably 500 or more. The upper limit of the molecular weight is preferably 100,000 or less, more preferably 80,000 or less, and particularly preferably 50,000 or less. Commercially available products commonly available as food ingredients can be used in the present invention.

[0061] (ceramide) Ceramide is an amide bond between sphingosine and a fatty acid. Examples of ceramides include plant-derived ceramides, animal-derived ceramides, and human ceramides. Examples of plant-derived ceramides include ceramides derived from rice, soybeans, peaches, corn, wheat, and konjac. Examples of animal-derived ceramides include ceramides derived from the brains and spinal cords of cattle, horses, pigs, etc. The ceramide used in the present invention may be a glycoceramide, specifically, for example, a ceramide bonded to a monosaccharide such as galactosylceramide or glucosylceramide, or a ceramide bonded to an oligosaccharide. In the present invention, plant-derived ceramides are preferred, and rice-derived ceramide and konjac-derived ceramide are particularly preferred because of their excellent effect of improving sleep quality. In the present invention, commercially available products commonly available as food ingredients can be used.

[0062] (Hyaluronic acid) Hyaluronic acid is a type of mucopolysaccharide present in the skin, joints, vitreous body of the eye, etc. of humans and vertebrates, and is also known as hyaluronan.

[0063] The hyaluronic acid used in the present invention can be extracted from animal tissues such as chicken comb, or produced by microorganisms such as lactic acid bacteria. Chicken comb has long been used as food and is safe, so ground chicken comb can be used instead of hyaluronic acid. The molecular weight of the hyaluronic acid used in the present invention varies depending on the number and type of repeating units and is not limited. Hyaluronic acid with a weight-average molecular weight of several hundred to several million can be used, or hydrolyzed hyaluronic acid with an average molecular weight of 10,000 or less can be used. The hyaluronic acid used in the present invention can also be in the form of a salt. Examples of hyaluronic acid salts include sodium hyaluronate and potassium hyaluronate. In the present invention, commercially available products commonly available as food ingredients can be used.

[0064] (elastin) Elastin is a major elastic protein present together with collagen in mammals, birds, fish, etc., particularly in mammals' aorta, ligamentum nuchale, ligamentum flavum, lung, skin, uterus, elastic cartilage, etc., and is also known as elastic fiber. The elastin used in the present invention includes, in addition to water-soluble elastin, hydrolyzed elastin, α-elastin, κ-elastin, elastin peptides, etc.

[0065] Elastin can be extracted from animal tissues, such as connective tissues of mammals, birds, fish, etc., by hydrolyzing the elastin with acid or alkali or by enzymatic treatment. The elastin used in the present invention can be naturally derived, synthesized, or commercially available as a raw material for food and beverages. In the present invention, commercially available products that are commonly available as food raw materials can be used.

[0066] (Vitamin C) Vitamin C is a type of water-soluble vitamin, also known as L-ascorbic acid or ascorbic acid. Examples of vitamin C used in the present invention include ascorbic acid and its salts and derivatives. These may be used alone or in combination of two or more. Vitamin C is known to have antioxidant properties and protect cells from damage caused by free radicals. In the present invention, commercially available products that are commonly available as food ingredients can be used.

[0067] The content of the specific components (a) to (c) in the sleep quality improving composition of the present invention is not particularly limited, and is, for example, preferably 0.0001% by mass or more, more preferably 0.0005% by mass or more, and particularly preferably 0.001% by mass or more in terms of its excellent effect of improving sleep quality. Furthermore, the content is preferably 95% by mass or less, more preferably 90% by mass or less, and particularly preferably 80% by mass or less in terms of its excellent effect of improving sleep quality. When a plurality of specific components (a) to (c) are contained, the content of the specific components (a) to (c) refers to their total amount.

[0068] The blending ratio of cannabidiol to specific components (a) to (c) in the sleep quality improving composition of the present invention is not particularly limited, and for example, cannabidiol:specific components (a) to (c) is preferably 1:0.01 to 10,000,000, more preferably 1:0.1 to 1,000,000, and from the viewpoint of excellent sleep quality improving effect, cannabidiol:specific components (a) to (c) is particularly preferably 1:0.1 to 100,000. When a plurality of specific components (a) to (c) are contained, the amount of specific components (a) to (c) is the total amount thereof.

[0069] The content of cannabidiol in the sleep quality improving composition of the present invention relative to the total amount of cannabidiol and specific components (a) to (c) is, for example, preferably 0.0001% by mass or more, more preferably 0.0005% by mass or more, and particularly preferably 0.001% by mass or more in terms of its excellent effect of improving sleep quality. The content is preferably 80% by mass or less, more preferably 70% by mass or less, and particularly preferably 50% by mass or less in terms of its excellent effect of improving sleep quality. When a plurality of specific components (a) to (c) are contained, the amount of specific components (a) to (c) is the total amount thereof.

[0070] The daily usage amount of the composition for improving sleep quality of the present invention is not particularly limited and can be appropriately set depending on the mode of use, the content of use by the user, etc. For example, the daily usage amount of the composition for improving sleep quality of the present invention is preferably 0.1 to 1000 mg / kg, more preferably 1 to 500 mg / kg, converted to solid content based on the body weight of the user, and even more preferably 2 to 100 mg / kg, from the viewpoint of exerting the effects of the composition for improving sleep quality of the present invention.

[0071] Similarly, the amount of the composition for improving sleep quality of the present invention used per administration is not particularly limited. For example, the amount of the composition for improving sleep quality of the present invention used per administration is preferably 0.01 to 2000 mg / kg, more preferably 0.1 to 1000 mg / kg, calculated as solid content based on the body weight of the user, and even more preferably 0.2 to 50 mg / kg, from the viewpoint of exerting the effects of the composition for improving sleep quality of the present invention.

[0072] Furthermore, the daily usage amount of the composition for improving sleep quality of the present invention is not particularly limited, and for example, in terms of solid content, it is preferably 0.001 to 20 g, more preferably 0.01 to 10 g, and from the viewpoint of exerting the effects of the composition for improving sleep quality of the present invention, it is particularly preferably 0.1 to 5 g.

[0073] The amount of the composition for improving sleep quality of the present invention to be used per time is not particularly limited, and is, for example, preferably 0.0001 to 20 g, more preferably 0.001 to 10 g, in terms of solid content, and particularly preferably 0.01 to 5 g, from the viewpoint of exerting the effects of the composition for improving sleep quality of the present invention.

[0074] Furthermore, the amount of cannabidiol contained in the daily use amount of the composition for improving sleep quality of the present invention is not particularly limited, and is, for example, preferably 0.00001 to 1 g, more preferably 0.00005 to 0.5 g, and from the viewpoint of exerting the effects of the composition for improving sleep quality of the present invention, particularly preferably 0.0001 to 0.1 g.

[0075] The amount of cannabidiol contained in a single dose of the composition for improving sleep quality of the present invention is not particularly limited, and can be, for example, 0.000001 to 1 g, more preferably 0.000005 to 0.5 g, in terms of solid content, and from the viewpoint of exerting the effects of the composition for improving sleep quality of the present invention, particularly preferably 0.00001 to 0.1 g.

[0076] The composition for improving sleep quality of the present invention has the effect of improving sleep quality, as described in the Examples below. Note that improving sleep quality in the present invention is a concept that includes improving (improving) sleep quality and / or suppressing (maintaining) a decline in sleep quality.

[0077] In the present invention, sleep quality is indicated by at least one item selected from the group consisting of, for example, sleepiness upon waking, sleep onset and sleep maintenance (e.g., smooth sleep onset and sleep maintenance, or falling asleep quickly and continuing a stable sleep without waking up during the night), dreaminess (e.g., not having frequent dreams or nightmares), fatigue upon waking, waking up during the night, daytime sleepiness, sleep rhythm, depth of sleep, and satisfaction with sleep (e.g., not feeling short of time).

[0078] The composition for improving sleep quality of the present invention has the effect of improving sleep quality, for example, reducing sleepiness upon waking, facilitating sleep onset, increasing sleep time, reducing dreaminess, reducing fatigue upon waking, shortening the time spent awake during the night, reducing daytime sleepiness, improving sleep rhythm, increasing the depth of sleep, and improving satisfaction with sleep.

[0079] The effect of improving sleep quality can be evaluated by a conventionally known method without any particular limitation, for example, by the OSA sleep questionnaire, VAS, etc.

[0080] There are no particular limitations on the composition for improving sleep quality, as long as it contains cannabidiol and specific ingredients and can be distinguished from other products in that it has the function of improving sleep quality.For example, the scope of the present invention includes products that display the function of improving sleep quality on the main body, packaging, instructions, or promotional materials (advertising media) of the product of the present invention.

[0081] Specifically, examples include health foods that claim to "improve sleep quality," "improve sleep quality (depth of sleep, satisfaction with sleep upon waking)," "improve feeling of deep sleep," "reduce the number of awakenings during sleep," "reduce the time spent waking during sleep," "improve sleep depth," "improve satisfaction with sleep depth," "improve sleep rhythm," "improve daytime sleepiness," "relieve daytime sleepiness," "reduce sleepiness during activities," "improve satisfaction upon waking," "improve feeling of extended sleep time," "support quality sleep at night," "sleep support," "improve sleep," "reduce sleepiness upon waking," "reduce fatigue upon waking," "support quality sleep," "improve satisfaction with sleep," "satisfaction upon waking," "improve falling asleep," "provide a feeling of having slept longer," "improve dreaminess," "reduce awakenings during the night," "improve sleep rhythm," etc., as well as health foods that claim to have the listed functions. Furthermore, functional foods also include those that claim that improving sleep quality is scientifically justified as their functionality.

[0082] The sleep quality improving composition of the present invention may be one that lists cannabidiol and / or a specific ingredient as the active ingredient, but is not limited to one that lists cannabidiol or a specific ingredient as the active ingredient on the product packaging, etc. For example, it may be one that does not specify the active ingredient. Furthermore, even general foods that are manufactured and sold with a suggested use are included within the scope of the present invention. For example, foods sold with personal testimonials from people who have consumed the product, mentioning its improvement in sleep quality, posted on a website, etc., are also included within the scope of the present invention.

[0083] In addition to cannabidiol and specific components, other components may be added to the sleep quality improving composition of the present invention as needed. When taken orally, other components may include, for example, dietary fiber such as soluble dietary fiber or insoluble dietary fiber, protein, various vitamins and minerals other than vitamin C, microorganisms such as algae, lactic acid bacteria, and yeast. Furthermore, if needed, commonly used ingredients in the food industry, such as dextrin, starch, and other sugars, oligosaccharides, sweeteners, acidulants, nutritional supplements, stabilizers, lubricants, binders, glazing agents, thickeners, colorants, excipients, diluents, bulking agents, emulsifiers, food additives, and seasonings, may be included. The content of these other components may be appropriately selected depending on the form of the composition of the present invention.

[0084] For transdermal administration, other ingredients that can be blended include, for example, active ingredients such as water, moisturizers, dispersants, plasticizers, spreading agents, preservatives, fragrances, pH adjusters, deodorants, chelating agents, antioxidants, antibacterial agents, antibacterial and antifungal agents, anti-inflammatory agents, and whitening agents, as well as cosmetic ingredients and medicinal ingredients such as animal extracts and plant extracts. The content of these other ingredients can be appropriately selected depending on the form of the composition of the present invention.

[0085] The sleep quality improving composition of the present invention can be used for both oral and parenteral applications. Parenteral compositions include compositions for external use on the skin, as well as compositions administered by direct administration to the stomach using a catheter or the like. The composition of the present invention is preferably for oral administration, as this allows the effects of the present invention to be easily achieved.

[0086] When used as an oral composition, its form may be, for example, a tablet, capsule, powder, granule, liquid, granule, bar, plate, block, solid, pill, paste, cream, caplet, gel, chewable, or stick. Among these, tablets, capsules, powder, granule, and liquid forms are particularly preferred. Examples of oral compositions used as tablets, capsules, powders, granules, or liquids include supplements; food additives; packaged beverages filled in PET bottles, cans, bottles, or the like; and powdered beverages to be dissolved in water (hot water), milk, fruit juice, or the like. These are preferred because they are easy to consume during meals and can be palatable.

[0087] When the sleep quality improving composition of the present invention is a composition for external application to the skin, the composition may be in the form of, for example, a liquid, emulsion, cream, ointment, paste, gel, wax, or the like.

[0088] Specific examples of oral compositions for improving sleep quality include foods as edible compositions. Examples of foods include tea bags, breads, confectioneries, noodles, and other foods, as well as cooked foods. Examples of breads and confectioneries include breads such as white bread, sweet buns, French bread, English bread, muffins, steamed buns, donuts, and waffles; cakes such as butter cake, sponge cake, chiffon cake, and pancakes; frozen desserts such as chocolate, sorbet, and ice cream; jellies; and cookies. Examples of noodles include udon and somen noodles. Examples of cooked foods include soups such as curry, stew, miso soup, and vegetable soup, as well as their bases and seasonings.

[0089] The packaging form of the composition for improving sleep quality of the present invention is not particularly limited and can be selected appropriately depending on the dosage form, etc., but examples include blister packs such as PTPs; strip packaging; heat seals; aluminum pouches; film packaging using plastics, synthetic resins, etc.; glass containers such as vials; and plastic containers such as ampoules. [Example]

[0090] The present invention will be described below based on examples. <Test substance> The following substances were used as test substances. Cannabidiol: Commercially available powder Valerian: A dried powder of hydroethanolic extract of valerian root was used. Daylily: A dried powder of the water extract of daylily leaves was used. Passiflora incarnata: A dried powder of the hydroethanol extract of the aerial parts of Passiflora incarnata was used. Chamomile: Dried powder of hydroethanolic extract of chamomile flowers Tryptophan: Commercially available L-tryptophan was used. Glycine: Commercially available glycine was used. Valine: Commercially available L-valine was used. Leucine: Commercially available L-leucine was used Isoleucine: Commercially available L-(+)-isoleucine was used. Lysine: Commercially available L-lysine monohydrochloride was used. Methionine: Commercially available L-methionine was used. Phenylalanine: Commercially available L-(-)-phenylalanine was used. Threonine: Commercially available L-threonine Histidine: Commercially available L-histidine was used. Theanine: Commercially available L-theanine γ-aminobutyric acid: γ-aminobutyric acid obtained by fermenting barley with lactic acid bacteria Sesamin: Commercially available sesamin α-Glycerylphosphorylcholine: Commercially available soybean-derived α-glycerylphosphorylcholine was used. Collagen: Made with dried powder of hydrolyzed collagen (collagen peptides) derived from fish Ceramide: Made with dried powder of glucosylceramide derived from rice Hyaluronic acid: Sodium hyaluronate powder obtained by fermentation Elastin: Dried powder of elastin obtained by hydrolysis of fish Vitamin C: Commercially available sodium L-(+)-ascorbate

[0091] <Inhibition of intracellular calcium uptake by the addition of glutamic acid> 1. Preparation of Test Substances Cannabidiol: Dissolved in surfactant (PEG40-hydrogenated castor oil) at 70°C and diluted with medium to the desired concentration. Valerian, daylily, passionflower, and sesamin: Dissolved in DMSO and diluted with medium to the desired concentration. Other test substances: Diluted with medium to the specified concentration. The test substance-containing medium was finally prepared as 0.004% PEG40-hydrogenated castor oil-0.5% DMSO-10% FBS-RPMI1640 medium.

[0092] 2. Evaluation of the inhibitory effect of glutamate on intracellular calcium uptake (1) Rat adrenal pheochromocytoma cells (PC12, JCRB Cell Bank) were cultured in 10% HS-5% FBS-RPMI1640 medium and seeded onto a collagen-coated 96-well plate at 100 μL / well in 10% FBS-RPMI1640 medium at 4 × 10^4 cells / well. The cells were pre-cultured for 24 hours in a 37°C, 5% CO2 incubator. (2) After 24 hours of incubation, 100 μL / well of the test substance-containing medium was added to the medium already in the wells, and the cells were incubated for 24 hours in a 37°C, 5% CO2 incubator. All test substances were prepared at 1 μg / mL and mixed at the ratios shown in Tables 1 and 2 below (final test substance concentration: 0.5 μg / mL in total). (3) Intracellular calcium was measured using the Calcium-Kit Fura2 (Dojindo Laboratories). The medium was removed from the cells in (2), and 100 μL of loading buffer was added and cultured for 1 hour. The loading buffer was removed, and 90 μL of recording buffer was added. The cells were then allowed to acclimate in an incubator for 10 minutes. (4) Next, 10 μL of 100 mM glutamic acid was added to a final concentration of 10 mM, and the fluorescence intensities Ftest(340) and Ftest(380) (excitation wavelengths 340 and 380 nm, fluorescence wavelength 510 nm) were measured 1 minute after addition. The fluorescence intensities Fpre(340) and Fpre(380) immediately before the addition of glutamic acid were also measured. After the test, MnCl2 was added to a final concentration of 0.33 M, and the fluorescence intensities Fblank(340) and Fblank(380) were measured to calculate the autofluorescence. Using the above measured values, the change in the fluorescence intensity ratio was calculated according to the following formula. Rtest=(Ftest(340) - Fblank (340)) / (Ftest(380) - Fblank (380)) Rpre=(Fpre(340) - Fblank (340)) / (Fpre(380) - Fblank (380)) Change in fluorescence intensity ratio = Rtest - Rpre (5) The change in the fluorescence intensity ratio of the control without the addition of the test substance was set to 1, and the relative value was calculated to evaluate the inhibitory effect of the addition of glutamic acid on intracellular calcium uptake. The results are shown in Tables 1 and 2.

[0093] [Table 1]

[0094] [Table 2]

[0095] One of the factors that reduces the quality of sleep is neural hyperexcitability. When NMDA receptors (glutamate receptors, an excitatory amino acid) on the surface of nerve cells are activated by the excitatory amino acid glutamate, a large amount of calcium ions flow into the nerve cells, which then activates various calcium ion-dependent enzymes, causing neural hyperexcitability. We evaluated the inhibitory effect of adding glutamate on intracellular calcium uptake in rat adrenal pheochromocytoma cells, which are widely used as a neural model cell. We found that a strong inhibitory effect on intracellular calcium uptake is believed to be a strong effect on improving sleep quality. Comparative Examples 1-5 and Examples 1-4 show that the oral compositions of the present invention, containing cannabidiol and at least one selected from valerian, daylily, passionflower, and chamomile, exhibited a higher inhibitory effect on intracellular calcium uptake than when each was used alone. Comparative Examples 1, 6-17, and Examples 5-16 show that the oral compositions of the present invention, containing cannabidiol and at least one selected from tryptophan, glycine, valine, leucine, isoleucine, lysine, methionine, phenylalanine, threonine, histidine, theanine, and γ-aminobutyric acid, exhibited a higher inhibitory effect on intracellular calcium uptake than when each was used alone. Furthermore, Examples 24-26 show that the use of cannabidiol and two or three selected from tryptophan, theanine, and γ-aminobutyric acid exhibited a higher inhibitory effect on intracellular calcium uptake than when each was used alone, as well as when each was used alone. Furthermore, Comparative Examples 1, 18-24 and Examples 17-23 show that the oral composition of the present invention, which contains cannabidiol and at least one selected from sesamin, α-glycerylphosphorylcholine, collagen, ceramide, hyaluronic acid, elastin, and vitamin C, exhibits a higher inhibitory effect on intracellular calcium uptake than when each component is used alone. These results demonstrate that the oral composition of the present invention provides an excellent effect in improving sleep quality, as the combination of cannabidiol and a specific component enhances the inhibitory effect on intracellular calcium uptake caused by the addition of glutamic acid.

[0096] <Production Examples 1 to 4> A granular composition for improving sleep quality was produced according to the formulation shown in Table 3. The composition for improving sleep quality obtained in the following production example has an excellent effect of improving sleep quality, and taking 2 g once a day provides an excellent effect of improving sleep quality.

[0097] [Table 3]

[0098] <Production Examples 5 to 8> Tablet-shaped compositions for improving sleep quality (250 mg per tablet) were produced according to the composition shown in Table 4 below. The compositions for improving sleep quality obtained in the following production examples have excellent effects in improving sleep quality, and taking two tablets once a day provides excellent effects in improving sleep quality.

[0099] [Table 4]

[0100] <Production Examples 9-11> Granules were prepared according to the composition shown in Table 5 below and encapsulated in a pullulan hard capsule shell to produce a capsule-shaped composition for improving sleep quality (250 mg per capsule; 180 mg granules, 70 mg capsule). The composition for improving sleep quality obtained in the following production example has an excellent effect in improving sleep quality, and taking one capsule twice a day can provide an excellent effect in improving sleep quality.

[0101] [Table 5]

[0102] <Production Examples 12-14> According to the composition shown in Table 6 below, the soft capsule content liquid was prepared and enclosed in a soft capsule shell made of pork gelatin to produce a capsule-shaped composition for improving sleep quality (350 mg per capsule; content liquid 220 mg, shell 130 mg). The composition for improving sleep quality obtained in the following production example has an excellent effect in improving sleep quality, and taking two capsules once a day will provide an excellent effect in improving sleep quality.

[0103] [Table 6]

[0104] <Production Examples 15-17> An oily composition for improving sleep quality was produced according to the formulation shown in Table 5 below. The composition for improving sleep quality obtained in the following production example has an excellent effect of improving sleep quality, and taking 5 mL once a day can provide an excellent effect of improving sleep quality.

[0105] [Table 7] [Industrial Applicability]

[0106] The composition for improving sleep quality of the present invention contains cannabidiol and specific ingredients, thereby providing a composition for improving sleep quality that has excellent effects in improving sleep quality, and has high potential for industrial use.

Claims

1. A composition for improving sleep quality, comprising cannabidiol and at least one component selected from the following (a) to (c): (a) Plant treatments (b) amino acids (c) Functional ingredients

2. 2. The composition for improving sleep quality according to claim 1, wherein (a) the plant treatment is at least one selected from the group consisting of valerian, daylily, passionflower, and chamomile.

3. The composition for improving sleep quality according to claim 1, characterized in that (b) the amino acid is at least one selected from tryptophan, glycine, valine, leucine, isoleucine, lysine, methionine, phenylalanine, threonine, histidine, theanine, and γ-aminobutyric acid.

4. The composition for improving sleep quality according to claim 1, characterized in that (c) the functional ingredient is at least one selected from sesamin, α-glycerylphosphorylcholine, collagen, ceramide, hyaluronic acid, elastin, and vitamin C.

5. 2. The composition for improving sleep quality according to claim 1, wherein the improvement in sleep quality is at least one selected from the reduction of sleepiness upon waking, promotion of sleep onset, increase in sleep time, reduction in dreaminess, reduction in fatigue upon waking, reduction in the time spent awake during the night, reduction in daytime sleepiness, improvement in sleep rhythm, improvement in the depth of sleep, and improvement in satisfaction with sleep.

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