Classifications

• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/01—Hydrocarbons
  • A61K31/015—Hydrocarbons carbocyclic
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/31—Hydrocarbons
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/007—Pulmonary tract; Aromatherapy
  • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
  • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P11/00—Drugs for disorders of the respiratory system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/20—Hypnotics; Sedatives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P3/00—Drugs for disorders of the metabolism
  • A61P3/02—Nutrients, e.g. vitamins, minerals
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Definitions

• the present invention relates to caryophyllene-containing compositions and the like. More specifically, compositions containing caryophyllene for treating respiratory diseases, compositions for preventing respiratory diseases, compositions for improving sleep, compositions for reducing fatigue, compositions for improving complexion, compositions for improving skin quality, The present invention relates to a composition for treating periodontal disease, a composition for suppressing bad breath, and the like.
• ⁇ -caryophyllene has the effect of relieving anxiety (Japanese Unexamined Patent Publication No. 2006-342062 (Patent Document 1)). Furthermore, it is known that feed containing ⁇ -caryophyllene is effective in improving stress in poultry and livestock (Japanese Patent Laid-Open No. 2008-19251 (Patent Document 2)).
• compositions that can treat or prevent respiratory diseases, compositions that can improve sleep or promote sleep induction, compositions that can reduce fatigue, compositions that can improve complexion, compositions that can improve skin quality There is a need for a composition that can treat or prevent periodontal disease or a composition that can suppress bad breath.
• methods that can treat or prevent respiratory diseases, methods that can improve sleep or promote sleep induction, methods that can reduce fatigue, methods that can improve complexion, methods that can improve skin quality, methods that can treat or prevent periodontal disease Alternatively, there is a need for a method that can suppress bad breath.
• the present invention includes inventions of the following aspects.
• a composition for treating or preventing a respiratory disease comprising caryophyllene.
• a cigarette comprising the cigarette filter according to [12].
• a smoking device comprising the cigarette filter according to [12].
• a method for treating or preventing a respiratory disease the method comprising administering a composition containing caryophyllene.
• a method for reducing fatigue comprising administering a composition comprising caryophyllene.
• a method for improving complexion comprising administering a composition containing caryophyllene.
• a method for improving skin quality comprising administering a composition containing caryophyllene.
• a method for treating periodontal disease or a method for preventing periodontal disease which comprises administering a composition containing caryophyllene.
• a method for controlling bad breath comprising administering a composition containing caryophyllene.
• a composition comprising caryophyllene for use in the treatment or prevention of respiratory diseases [31] A composition comprising caryophyllene for use in improving sleep or promoting sleep induction. [32] A composition comprising caryophyllene for use in reducing fatigue. [33] A composition comprising caryophyllene for use in improving complexion. [34] A composition containing caryophyllene for use in improving skin quality. [35] A composition comprising caryophyllene for use in periodontal disease treatment or periodontal disease prevention. [36] A composition comprising caryophyllene for use in halitosis control. In this specification, "%" indicates mass percent unless otherwise specified.
• a composition that can treat or prevent respiratory diseases a composition that can improve sleep or promote sleep induction, a composition that can reduce fatigue, a composition that can improve complexion, and a composition that can improve skin quality.
• Compositions that can improve periodontal disease, compositions that can treat or prevent periodontal disease, compositions that can suppress bad breath, etc. can be provided.
• a method for treating or preventing respiratory diseases a method for improving sleep or promoting sleep induction, a method for reducing fatigue, a method for improving complexion, and a method for improving skin quality.
• a method for treating or preventing periodontal disease, and a method for suppressing bad breath a method for treating or prevent respiratory diseases, a composition that can improve sleep or promote sleep induction, a composition that can reduce fatigue, a composition that can improve complexion, and a composition that can improve skin quality.
• the upper and lower limits can be arbitrarily combined.
• a numerical range is described as “preferably 3.0 to 15, more preferably 3.2 to 13"
• the range is “3.0 to 13" or "3.2 to 15”.
• Ranges are also included within the numerical ranges set forth herein.
• the numerical range is described as "preferably 30 or more, more preferably 40 or more, and preferably 100 or less, more preferably 80 or less", “30 to 80”
• the range and the range "40 to 100" are also included in the numerical ranges described herein.
• the description "60 to 100” means a range of "60 or more (60 or more than 60) and 100 or less (100 or less than 100)". do.
• the numerical range from the lower limit value to the upper limit value can be defined by appropriately selecting from each option and combining them arbitrarily.
• a plurality of the various requirements described as preferred embodiments described herein can be combined.
• composition of one aspect of the invention includes caryophyllene.
• caryophyllene examples include ⁇ -caryophyllene, ⁇ -caryophyllene, isocaryophyllene, metabolites or derivatives of caryophyllene (eg, caryophyllene oxide such as ⁇ -caryophyllene oxide), and the like.
• the composition of one embodiment of the present invention may contain these alone or in combination of two or more.
• caryophyllene preferably contains ⁇ -caryophyllene, and may further contain caryophyllene other than ⁇ -caryophyllene [for example, at least one selected from ⁇ -caryophyllene, isocaryophyllene, and metabolites or derivatives of caryophyllene].
• the proportion of ⁇ -caryophyllene in the whole caryophyllene is, for example, 30% by mass or more, 50% by mass or more, 70% by mass or more, 80% by mass or more, 90% by mass or more, 95% by mass or more. It may be greater than or equal to 100% by mass (substantially 100% by mass).
• the term " ⁇ -caryophyllene" may be used as a general term to include caryophyllenes other than ⁇ -caryophyllene.
• Caryophyllenes such as ⁇ -caryophyllene are not particularly limited, and include, for example, clove, caraway, basil, oregano, hop, cinnamon, Ceylon Nikkei, rosemary, hemp, hemp, cannabis, black pepper, lavender, marabatrum, ylang-ylang, It may be derived from copaiba, Guinea ginger, curry leaf, essential oils thereof, etc. (for example, it may be extracted or concentrated).
• caryophyllene may be a commercially available product, or may be produced (purified) by a conventional method (chemically synthesized).
• Commercially available ⁇ -caryophyllene includes, for example, caryophyllene AKY-2348 (trade name: Rilak Phyton (registered trademark)) manufactured by Inabata Kogyo Co., Ltd.
• the content of caryophyllene in the composition of one embodiment of the present invention is not particularly limited, but may be determined as appropriate depending on desired functions (e.g., volatilization promotion, dissolution promotion, freezing resistance, and caryophyllene functions, etc.), dosage form, etc. You can choose.
• the content (ratio, concentration) of caryophyllene is 0.01% by mass or more, 0.05% by mass or more, 0.1% by mass or more, 0.5% by mass or more.
• the range of the concentration (proportion) of caryophyllene may be set by appropriately combining the lower and upper limits of the above range (for example, 0.1 to 90% by mass, 10 to 50% by mass, etc.). (The same applies to all descriptions of ranges in the specification.) Therefore, the content of caryophyllene in the composition of one embodiment of the present invention is, for example, 1% by mass or more, 3 to 99% by mass, 5 to 80% by mass, 5 to 90% by mass, 15 to 30% by mass, etc. Can be mentioned.
• the concentration range of caryophyllene in the above composition (for example, 1% by mass or more, 10% by mass or more, 5-90% by mass, etc.).
• the daily intake of caryophyllene is not particularly limited, but for example, 0.1 mg or more, 0.5 mg or more, 1.0 mg or more, 2.0 mg or more, 3.0 mg or more, 4.0 mg or more, 5.0 mg or more, 6.0 mg or more, 7.0 mg or more, 10.0 mg or more, 15.0 mg or more, 20.0 mg or more, 30.0 mg or more, 40.0 mg or more, 50.0 mg or more, 60.0 mg or more, 70.0 mg or more, 80.0 mg or more, 90.0 mg or more, 100.0 mg or more, 150.0 mg or more, 200.0 mg or more, 250.0 mg or more, 300.0 mg or more, 350.0 mg or more, 400.0 mg or more, 450.0 mg or more, 500.0mg or more, 550.0mg or more, 600.0mg or more, 650.0mg or more, 700.0mg or more, 750.0mg or more, 800.0mg or more, 850.0mg or more, 900.0mg or more, 950.0mg or more, 1000.0mg
• composition may contain other components depending on its form, use, application target, etc., such as oils and fats, carriers, excipients, binders, disintegrants, lubricants, and coatings. agents, colorants, stabilizers, emulsifiers (surfactants), absorption enhancers, gelling agents, pH adjusters, preservatives, antioxidants, cooling agents, physiologically active substances, biologically active substances, microorganisms, Examples include foods and drinks, plants, sweeteners, acidulants, seasonings, tonics, and fragrances. These components may be used alone or in combination of two or more.
• oils and fats examples include vegetable oils (e.g., soybean oil, rapeseed oil, corn oil, sesame oil, linseed oil, cottonseed oil, perilla oil, olive oil, rice oil, palm oil, jojoba oil, sunflower oil, camellia oil, etc.), animal oils (e.g., (beef tallow, pork fat, chicken fat, milk fat, fish oil, horse oil, etc.), medium chain fatty acid triglycerides (MCT), and the like.
• the number of carbon atoms in the fatty acid contained in MCT is preferably 5 to 15, more preferably 6 to 14, and still more preferably 6 to 12.
• oils and fats may be used alone or in combination of two or more.
• MCT may be particularly preferably used. Therefore, the oil or fat may contain at least MCT.
• the proportion of MCT to the whole fat is, for example, 10% by mass or more, 30% by mass or more, 50% by mass or more, 70% by mass or more, 80% by mass or more, 90% by mass or more, It may be 100% by mass (MCT only) or the like.
• Oils and fats can function as a medium (solvent, carrier) for compositions, and depending on the type (for example, MCT, etc.), oils and fats have relatively low volatility and solubility of fragrances, and freezing resistance of fragrances and fats themselves. In many cases, it is good (or does not decrease significantly), and from this point of view, a part of caryophyllene etc. can be suitably replaced with fats and oils (in particular, MCT etc.). Furthermore, the use of fats and oils (MCT, etc.) can be advantageous in terms of encapsulation and the like. Furthermore, fats and oils appear to have little effect on aroma and are easy to use in combination with perfumes and caryophyllene.
• the proportion (amount, concentration) of fats and oils is, for example, 0.1% by mass or more (for example, 0.5% by mass or more), 1% by mass or more (for example, 5% by mass or more). ), 10% by mass or more (for example, 15% by mass or more), 20% by mass or more (for example, 25% by mass or more), 30% by mass or more (for example, 35% by mass or more), 40% by mass or more (for example, 45% by mass or more) % or more), 50 mass% or more (e.g., 55 mass% or more), 60 mass% or more (e.g., 65 mass% or more), 70 mass% or more (e.g., 75 mass% or more), 80 mass% or more (e.g., 85% by mass or more), 90% by mass or more (for example, 95% by mass or more), etc., and 99% by mass or less (for example, 95% by mass or less), 90% by mass or less, 80% by mass or less, 70% by mass
• the carrier that may be included in the composition of one embodiment of the present invention is not particularly limited, but includes, for example, acids (e.g., fatty acids such as caprylic acid, capric acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid, and linoleic acid), Hydrocarbons (e.g., liquid paraffin, squalane, petrolatum), silicones (e.g., silicone oil, etc.), synthetic polymers (e.g., polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, polyvinylpyrrolidone, etc.), natural polymers, or derivatives thereof (e.g.
• acids e.g., fatty acids such as caprylic acid, capric acid, eicosapentaenoic acid, docosahexaenoic acid, oleic acid, and linoleic acid
• Hydrocarbons e.g., liquid paraffin,
• carrageenan alginic acid, cellulose, guar gum, xanthan gum, quince seed, dextran, gellan gum, hyaluronic acid, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, cationized guar gum, acetylated hyaluronic acid, sodium alginate, etc.
• lower Examples include alcohols (eg, ethanol, isopropanol, etc.), polyhydric alcohols (eg, ethylene glycol, glycerin, propylene glycol, butylene glycol, diglycerin, dipropylene glycol), water, and the like.
• the nature of the carrier can be selected depending on the form of the composition, etc., and may be solid, liquid, etc., and may be nonvolatile or volatile.
• a liquid carrier can also be called a solvent.
• Emulsifiers that may be included in the composition of one embodiment of the present invention are not particularly limited, but examples include nonionic surfactants [e.g., sugar fatty acid esters (e.g., sucrose fatty acid esters, maltose fatty acid esters)] , lactose fatty acid ester), propylene glycol fatty acid ester, glycerin fatty acid ester, sorbitan fatty acid ester, polyglycerin fatty acid ester, organic acid monoglyceride], and the like.
• nonionic surfactants e.g., sugar fatty acid esters (e.g., sucrose fatty acid esters, maltose fatty acid esters)] , lactose fatty acid ester), propylene glycol fatty acid ester, glycerin fatty acid ester, sorbitan fatty acid ester, polyglycerin fatty acid ester, organic acid monoglyceride], and the like.
• the proportion (concentration) of the emulsifier in the composition can be selected depending on the aspect, application, etc. of the composition, and is not particularly limited, but for example, 40% by mass or less (for example, 35% by mass or less) For example, 30% by mass or less (for example, 25% by mass or less), preferably 20% by mass or less (for example, 15% by mass or less), more preferably 10% by mass or less (for example, 8% by mass or less). 5% by mass or less (for example, 4% by mass or less, 3% by mass or less, 1% by mass or less, etc.).
• the lower limit of the proportion (concentration) of the emulsifier can be selected depending on the aspect of the composition, its use, etc., and is not particularly limited, but examples include 0.01% by mass, 0.1% by mass, 0.5% by mass, 0. It may be .7% by mass, 1% by mass, 1.2% by mass, 1.5% by mass, 2% by mass, 3% by mass, etc.
• Emulsifiers can significantly reduce interfacial tension in compositions. Therefore, when the composition is used as the contents of a capsule (for example, a seamless capsule manufactured by a dropping method), encapsulation is likely to be inhibited. From this point of view, when the composition is used as the contents of a capsule, it is desirable not to use (substantially not use) an emulsifier, but even if it is used, the proportion thereof is relatively small. (For example, 5% by mass or less, 3% by mass or less of the composition, etc.) is desirable.
• the composition of one aspect of the present invention includes dicarboxylic acid esters, diol esters, monocarboxylic acid esters, esters of polyols having 3 or more hydroxy groups, esters of polycarboxylic acids having 3 or more carboxyl groups, polyol ethers, polyamines. , and at least one component selected from alcohols having 6 or more carbon atoms.
• such components often have relatively good solubility of fragrances (for example, menthol-containing fragrances), freezing resistance of fragrances and fats and oils themselves, etc.
• fragrances for example, menthol-containing fragrances
• freezing resistance of fragrances and fats and oils themselves etc.
• Administration of the composition of one aspect of the invention may be oral, parenteral, pulmonary, intraperitoneal, intravenous, intraarterial, transdermal, sublingual, intramuscular, rectal, transbuccally, intranasally, Administration may take place in a wide range of routes including, but not limited to, via inhalation, intravaginally, intraocularly, via topical delivery, subcutaneously, intrafatally, intraarticularly and intrathecally. . In one particular variation, administration is oral or pulmonary.
• Oral administration may involve swallowing if the composition enters the bloodstream via the gastrointestinal tract.
• oral administration may involve mucosal administration (eg, buccal, sublingual, suplingual administration) in which the compound enters the bloodstream via the oral mucosa.
• Formulations suitable for oral administration include solid, semisolid, and liquid systems, such as tablets; soft or hard capsules, including multiparticulate or nanoparticles, liquids, powders, or liposomes; lozenges, which may be liquid filled; Chews; gels; fast-dispersing dosage forms; films; ovules; sprays; and intraoral or mucoadhesive patches.
• Liquid formulations include suspensions, solutions, syrups, and elixirs. Such formulations may be used as fillers in soft or hard capsules (e.g. made of gelatin or hydroxypropyl methylcellulose) and are usually combined with carriers (e.g. water, ethanol, polyethylene glycol, propylene glycol, methylcellulose, or a suitable oil). ) and one or more emulsifying agents, suspending agents, or both. Solutions may also be prepared by reconstitution of solids (eg, from sachets).
• any mode in which caryophyllene can be ingested can be adopted. Examples include breathing in a space where caryophyllene has been volatilized, and inhalation through an inhaler.
• An example of inhalation via an inhalation device is, for example, inhalation through a filter of an inhalation device (eg, smoking a cigarette with a caryophyllene-containing capsule in the filter).
• the caryophyllene may also be in a fast-dissolving, fast-disintegrating dosage form.
• the active pharmaceutical ingredient will be from about 1% to about 80% by weight of the dosage form, more typically from about 5% to about 5% by weight of the dosage form. It constitutes 60% by mass.
• tablets may contain one or more disintegrants, binders, diluents, surfactants, glidants, lubricants, antioxidants, colorants, flavors, preservatives, and corrigents. may be included.
• disintegrants examples include sodium starch glycolate, sodium carboxymethylcellulose, calcium carboxymethylcellulose, croscarmellose sodium, crospovidone, polyvinylpyrrolidone, methylcellulose, microcrystalline cellulose, C1-6 alkyl-substituted hydroxypropylcellulose, starch, alpha Examples include modified starch, and sodium alginate.
• the disintegrant will constitute from about 1% to about 25% or from about 5% to about 20% by weight of the dosage form.
• Binders are commonly used to impart cohesive properties to tablet formulations. Suitable binders include microcrystalline cellulose, gelatin, sugars, polyethylene glycols, natural and synthetic gums, polyvinylpyrrolidone, pregelatinized starch, hydroxypropylcellulose, and hydroxypropylmethylcellulose. Tablets may also contain diluents such as lactose (monohydrate, spray-dried monohydrate, anhydrous), mannitol, xylitol, dextrose, sucrose, sorbitol, microcrystalline cellulose, starch, and calcium hydrogen phosphate dihydrate. May contain Japanese products.
• Tablets may also contain surfactants, such as sodium lauryl sulfate and polysorbate 80, and glidants, such as silicon dioxide and talc. If included, surfactants may constitute from about 0.2% to about 5% by weight of the tablet, and glidants may comprise from about 0.2% to about 1% by weight of the tablet. .
• surfactants such as sodium lauryl sulfate and polysorbate 80
• glidants such as silicon dioxide and talc. If included, surfactants may constitute from about 0.2% to about 5% by weight of the tablet, and glidants may comprise from about 0.2% to about 1% by weight of the tablet. .
• Tablets may also contain lubricants, such as magnesium stearate, calcium stearate, zinc stearate, sodium stearyl fumarate, and mixtures of magnesium stearate and sodium lauryl sulfate.
• the lubricant may constitute from about 0.25% to about 10%, or from about 0.5% to about 3% by weight of the tablet.
• Tablet blends may be compressed directly or by roller compression to form tablets.
• the tablet blend or portions of the blend may be wet-, dry-, or melt-granulated, melt congealed, or extruded prior to tabletting.
• one or more of the ingredients may be separated by sieving, grinding, or both prior to blending.
• the final dosage form may contain one or more layers and may be coated, uncoated, or a capsule.
• Ingestible oral films for human or veterinary use are flexible water-soluble or water-swellable thin film dosage forms, which may be fast dissolving or mucoadhesive.
• typical films include one or more film-forming polymers, binders, wetting agents, plasticizers, stabilizers or emulsifiers, viscosity modifiers, and solvents.
• Other film ingredients include antioxidants, colorants, flavorings and flavor enhancers, preservatives, salivary gland stimulants, cooling agents, co-solvents (including oils), emollients, bulking agents, defoamers, surfactants. and flavoring agents.
• Some components of the formulation may serve more than one function.
• the amount of API in the film may depend on its solubility.
• the API typically comprises from about 1% to about 80% by weight of the non-solvent components (solutes) of the film, or from about 20% to about 50% by weight of the solutes of the film.
• the less soluble API may constitute a larger proportion of the composition, typically up to about 88% by weight of the non-solvent component of the film.
• the film-forming polymer can be selected from natural polysaccharides, proteins, or synthetic hydrocolloids and typically comprises from about 0.01% to about 99% or from about 30% to about 80% by weight of the film. Configure.
• Film dosage forms are usually prepared by evaporative drying of an aqueous thin film applied to a peelable support or support paper, which can be carried out in a drying oven or drying path (e.g., a composite coating-drying device), in a freeze-drying device, or in a freeze-drying device. May be carried out in a vacuum furnace.
• a drying oven or drying path e.g., a composite coating-drying device
• a freeze-drying device e.g., a freeze-drying device
• a freeze-drying device e.g., a freeze-drying device. May be carried out in a vacuum furnace.
• Formulations suitable for pulmonary administration include solid, semisolid, and liquid systems, such as tablets; multiparticulate or nanoparticles, liquids, powders, or liposomes.
• a liquid formulation and liquid formulations include suspensions, solutions, syrups, and elixirs. These formulations can be used as fillers in soft capsules (including seamless capsules) or hard capsules.
• Pulmonary administration can be performed using a cigarette (cigarette filter), a smoking device, an inhalation device, and the like.
• the dosage form of the composition of one aspect of the invention may be a capsule.
• the capsule may be composed of only a membrane (shell), but preferably includes a core and a shell.
• the capsule may be a soft capsule, a hard capsule, etc., or a seamless capsule (seamless capsule).
• capsules for tobacco and the like may be seamless capsules.
• the form of the composition is not particularly limited, and may be a film, a core, or both of these.
• the core at least the core is the composition. May contain.
• the film may normally contain film-forming components (film-forming base, film-forming agent).
• the film-forming component is not particularly limited and can be selected as appropriate depending on the intended use of the capsule.
• alkali metal salts sodium salts, potassium salts, etc.
• alkaline earth metal salts calcium salts, magnesium salts, etc.
• metal salts such as iron salts, tin salts, etc.
• resin-derived polysaccharides e.g. gum gati, gum arabic, etc.
• polysaccharides derived from microorganisms e.g. pullulan, welan gum, xanthan gum, gellan gum, etc.
• polysaccharides derived from plants e.g.
• gum tragacanth pectin, glucomannan, starch, polydextrose, dextrin, maltodextrin) , cyclodextrin, indigestible dextrin, etc.
• seed-derived polysaccharides e.g., guar gum or its derivatives (e.g., hydroxypropyl guar gum, cationized guar gum, guar gum decomposition products (guar gum enzymatic decomposition products, etc.)), tara gum, tamarind seeds gum, locust bean gum, psyllium seed gum, flaxseed gum, etc.], fermented polysaccharides (e.g., diutan gum, etc.), cellulose derivatives (e.g., hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, carboxymethylcellulose, etc.), chitosan, etc. ⁇ , Examples include synthetic resins (polyvinyl alcohol, etc.), proteins (eg,
• the film-forming component may be capable of forming a hydrophilic colloid, and depending on its type, may function as a plasticizer, sweetener, dietary fiber, filler, etc.
• a commercially available product may be used as the film-forming component.
• the film may contain plasticizers, colorants, sweeteners, fragrances, antioxidants, preservatives, and the like.
• the film may contain a plasticizer to adjust the strength of the film.
• plasticizers include polyhydric alcohols (e.g., (poly)alkylene glycols such as ethylene glycol, propylene glycol, polyethylene glycol, and polypropylene glycol; polyols having three or more hydroxyl groups such as glycerin), sugars [e.g.
• sugars e.g., glucose, fructose, glucose, galactose, etc.
• disaccharides e.g., sucrose, maltose, trehalose, coupling sugar, etc.
• oligosaccharides e.g., maltooligosaccharides, etc.
• sugar alcohols e.g., sorbitol
• polysaccharides or derivatives thereof e.g., starch, starch derivatives (e.g., polydextrose, dextrin, maltodextrin, indigestible dextrin, cyclodextrin ( ⁇ , ⁇ , or ⁇ ), cellulose derivatives (eg, hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, carboxy
• the core may be solid, liquid, etc., and particularly in capsules containing the composition of the present invention, the core may be liquid.
• the liquid state includes a colloidal state, an emulsion state, a jelly state, and the like.
• the core preferably contains caryophyllene, and further contains the other ingredients listed above (disintegrants, binders, diluents, surfactants, glidants, lubricants, antioxidants, colorants, flavoring agents, preservatives). , flavoring agents, etc.).
• the core may generally be insoluble (non-erodible) in the coating (or the part that comes into contact with the coating).
• the diameter (diameter, average diameter) of the capsule (or membrane) can be selected as appropriate depending on the type of capsule, use, etc., for example, 0.1 mm or more, 0.5 mm or more, 1 mm or more, 1.5 mm or more, 2 mm or more. etc., and may be 30 mm or less, 25 mm or less, 20 mm or less, 18 mm or less, 15 mm or less, 12 mm or less, 10 mm or less, 8 mm or less, etc.
• Specific capsule diameters include, but are not limited to, 2.8 mm, 3.0 mm, 3.4 mm, 3.5 mm, and 4.0 mm.
• the coating ratio (the ratio of the coating to the entire capsule (total amount of coating and inclusions)) is, for example, from a range of about 0.1 to 99% by mass (for example, 0.5 to 95% by mass). 1 to 90% by weight, preferably 1.5 to 80% by weight (e.g. 2 to 70% by weight), more preferably 2.5 to 60% by weight (e.g. 3 to 50% by weight). It may be a degree.
• the thickness of the film is not particularly limited, and may be, for example, 1 to 200 ⁇ m, 3 to 150 ⁇ m, 5 to 100 ⁇ m, etc.
• the capsule eg, a capsule with a core
• the capsule may be breakable (collapsible) (eg, easily disintegrable, easily destructible).
• the breaking strength depends on the diameter of the capsule, etc., but for example, it is 100 g or more, 200 g or more, 300 g or more, 400 g or more, 500 g or more, 600 g or more, 700 g or more, 800 g or more, 900 g or more, 1000 g or more, etc. There may be.
• the upper limit of the breaking strength of the capsule is not particularly limited, but may be, for example, 20,000 g or less, 15,000 g or less, 12,000 g or less, 10,000 g or less, etc.
• the breaking strength (g) is measured with a rheometer CR-500DX (measuring instrument, manufactured by Sun Scientific Co., Ltd.) at 22°C and 60% RH, and with a Rheo Data analyzer (Rheo Data analyzer for Win).
• Rheo Data analyzer Rheo Data analyzer for Win.
• physical property data automatic analysis software manufactured by Sun Scientific Co., Ltd.
• the ratio of breaking strength (g) to outer diameter (mm) (breaking strength/outer diameter) is not particularly limited, but is, for example, 200 or more (for example, more than 200), It is preferably 210 or more (for example, 220 or more), more preferably 230 or more (for example, 240 or more), 250 or more, 300 or more, 400 or more, etc.
• the upper limit of the ratio of breaking strength to outer diameter (breaking strength/outer diameter) is not particularly limited, and may be, for example, 20,000, 15,000, 10,000, 8,000, 6,000, 5,000, etc.
• the ratio of the breaking strength to the outer diameter is determined by the ratio of the breaking strength to the outer diameter. This can be said to be an index that reflects the ease of use.
• the breaking distance of the capsule may be, for example, 0.1 mm or more, 0.2 mm or more, 0.5 mm or more, 1.0 mm or more, etc., depending on the outer diameter and the like.
• the upper limit of the breaking distance of the soft capsule is not particularly limited, but may be, for example, 15 mm or less, 10 mm or less, 8 mm or less, etc.
• the fracture distance can be measured, for example, with a rheometer CR-3000EX (manufactured by Sun Scientific Co., Ltd.).
• the ratio of fracture distance (mm) to outer diameter (mm) is not particularly limited, but is, for example, 0.1 or more, preferably 0.12 or more, more preferably 0.15. or more, 0.18 or more, 0.2 or more, etc.
• the upper limit of the ratio of fracture distance to outer diameter (fracture distance/outer diameter) is not particularly limited, and may be, for example, 1.0, 0.98, 0.97, 0.96, 0.95, etc. .
• the capsule may be used as it is, depending on the intended use, or may be used in combination with other capsules, or may be incorporated into a filter as described below.
• capsules may be capsules that do not contain caryophyllene, such as capsules that are composed of a core and a shell, and that neither the core nor the shell contains caryophyllene.
• a known method can be used to manufacture capsules (eg, seamless capsules).
• the manufacturing method include methods described in Japanese Patent No. 5047285, Japanese Patent Publication No. 10-506841, Japanese Patent No. 5581446, and the like.
• an in-liquid dropping method using a dropping method using two or more nozzles there may be mentioned an in-liquid dropping method using a dropping method using two or more nozzles.
• Seamless capsules can be manufactured by filling the capsule film with the capsule liquid using this method, and then curing and drying the film.
• capsules examples include medicines, food and drink products, cigarettes, cigarette filters, smoking devices, and inhalation devices.
• a food/beverage product contains the composition of the present invention.
• Foods and beverages may be prepared as functional foods, health foods, foods for specified health uses, foods with health claims such as foods with nutritional functions, foods for special purposes (eg, foods for patients), health supplements, supplements, and the like.
• a supplement for example, tablets, rounds, capsules (including hard capsules, soft capsules, microcapsules, and seamless capsules), powder, granules, fine granules, and troches can be used together with various additives used in the manufacture of general supplements. It can be in the form of a liquid (including syrup, emulsion, suspension), etc.
• the food and drink products such as supplements according to one embodiment of the present invention include GABA, L-theanine, milk protein hydrolyzate, chamomile extract, bacopa monniera extract, St. John's wort extract, lemon balm extract, and yuzu seed extract.
• artichoke extract Scaletium tortuosum extract, Rhodiola rosea extract, hesperidin (monoglucosylhesperidin), holy basil extract, quail extract, valerian extract, passion flower extract, longan extract, saffron extract, horse whip extract, elastin, black soybean Seed coat extract, Hihatsu extract, cinnamon bark powder, cinnamon bark extract, rutin, quercetin, star fruit leaf extract, moon peach leaf extract, black turmeric extract, ginger (extract, powder), pine bark extract, blackcurrant extract, plum extract, amla extract, camellia seed extract , nattokinase, L-arginine, L-citrulline, tocotrienols, vitamin E, garlic, cocoa, capsicum extract, French maritime pine bark extract, seaweed extract, lafuma extract, crocetin, albacore bark extract, tart cherry extract, okra seed extract, France Oak extract, coenzyme Q10, moringa extract, olive leaf extract,
• Fennel/fenugreek extract blackcurrant polyphenols, grape seed extract, adlay extract, ⁇ -cryptoxanthin, hydroxylated isoflavones, broccoli sprout extract, Houta yam, hawthorn, Roman chamomile, grape leaf extract, xanthophyll derived from red paprika, lycopene, golden tomato extract , red orange extract, melon extract, maquili extract, parfia extract, fulvic acid, hexagonal extract, kiwi seed extract, bird's nest extract, rooibos extract, laurel extract, champignon extract, lactoferrin/lactoperoxidase, white curcumin, pumice extract, Persimmon tannin, manuka honey, phosphorylated oligosaccharide calcium, cyclic isomaltooligosaccharide, tea catechin, green tea fluoride, polyglutamic acid, mastic, cranberry, theafla
• the food and drink products of the present invention are not particularly limited, but include, for example, confectionery such as candy, gummies, and chewing gum; confectionery such as cookies, crackers, biscuits, chocolate, pudding, jelly, snack foods, rice crackers, steamed buns, and yokan.
• Frozen desserts such as ice cream, popsicles, sherbet, and gelato; Bakery foods such as donuts, cakes, white bread, French bread, and croissants; Noodles such as udon, soba, Chinese noodles, and kishimen; Rice products such as white rice, sekihan, and pilaf; Examples include sauces such as curry, stew, and dressing; paste products such as ham, sausage, kamaboko, chikuwa, and fish sausage; various side dishes such as tempura, croquettes, and hamburgers; and beverages such as juice and tea.
• the composition for treating or preventing respiratory diseases according to the present invention may be used as a food with functional claims such as "suppresses respiratory diseases” or “reduces discomfort in the throat and lungs.” Available.
• the composition for improving sleep or promoting sleep induction according to the present invention can be used in foods with functional claims such as "improving falling asleep,””improving/alleviating insomnia symptoms,” and the like.
• the fatigue-reducing composition according to the present invention can be used in food products with functional claims such as "alleviating fatigue” and "for those who have difficulty getting rid of fatigue.”
• the composition for improving complexion according to the present invention can be used in foods with functional claims such as "For those who are concerned about the complexion of their face.”
• the composition for improving skin quality according to the present invention can be used in foods with functional claims such as "improving rough skin.”
• the composition for treating periodontal disease or preventing periodontal disease according to the present invention can be used in a food with a functional claim such as "For those concerned about bleeding from the gums.”
• the composition for suppressing bad breath according to the present invention can be used in food products with functional claims such as "For those concerned about bad breath” and "Preventing bad breath.”
• the composition of one embodiment of the present invention can be used for tobacco; for example, the composition can be contained (adhered) to various parts of tobacco (tobacco leaves, filters, etc.). By using it in tobacco, caryophyllene can be administered through the lungs.
• Such embodiments include, for example, embodiments in which the composition is contained in tobacco leaves, etc. (e.g., cigarettes, cigars, pipes, kissels, smokeless tobacco (e.g., chewing tobacco, snuff, snuff, etc.)). ), etc.), an embodiment in which a filter containing the composition is used for cigarettes, and an embodiment in which a capsule (preferably a breakable (collapsed) capsule) containing the composition is placed in the filter.
• a capsule preferably a breakable (collapsed) capsule
• Capsules used for cigarettes are preferably composed of a core (content, liquid content, inclusions) and a shell (film, coating, capsule coating).
• Tobacco using the composition of one embodiment of the present invention is not particularly limited, and includes combustible tobacco (e.g., cigarettes, cigars, pipes, kissels, bongs), non-combustible tobacco (e.g., heated tobacco (directly heated tobacco), etc. (heating type, air heating type, etc.), smokeless tobacco, etc.).
• More specific embodiments include an embodiment in which the inhaled substance in a cigarette (for example, the liquid part in a smoking device) contains an optionally encapsulated composition (caryophyllene, menthol, etc.). By using it as an inhalant in this way, caryophyllene (and menthol) can be efficiently ingested through the lungs.
• the composition of the present invention may contain other components in addition to caryophyllene (furthermore, fats and oils and/or menthol), and usually includes a carrier [
• the carrier may contain a liquid carrier, such as a polyhydric alcohol (eg, glycerin, propylene glycol, etc.), and may further contain a flavoring agent (flavor liquid) if necessary.
• the proportion of caryophyllene, etc. may be selected from the same range as above.
• the usage mode of the composition is not particularly limited, and includes, for example, a mode in which the composition is contained (adhered) to various parts of the inhalation device.
• the inhalation device may contain the composition in the form of a capsule containing the composition.
• Caryophyllene can be administered pulmonary by using an inhalation device.
• Examples of inhalation devices include, but are not limited to, smoking devices.
• smoking devices include heating tobacco (vapor heating type, etc.), electronic cigarettes, pipes, kissels, bongs (water pipes, hookah tobacco), vaporizers, and the like.
• Heat-not-burn cigarettes allow you to ingest nicotine, and electronic cigarettes do not contain nicotine.
• heated tobacco include, but are not limited to, IQOS (Philip Morris), GLOW (British American Tobacco), Plume S, Plume Tech (Japan Tobacco), and Puls (Imperial Tobacco).
• Examples of electronic cigarettes include, but are not limited to, ego AIO (Joyetech) and ICE VAPE (Commonwealth).
• the inhaler is encapsulated in an inhalation material (e.g., liquid portion of a smoking device) in an inhalation device (e.g., smoking device such as heated tobacco (vapor heating type, etc.), electronic cigarette, bong, etc.).
• an inhalation device e.g., smoking device such as heated tobacco (vapor heating type, etc.), electronic cigarette, bong, etc.
• a composition that may be present is contained.
• the composition of the present invention may contain other components in addition to caryophyllene (furthermore, fats and oils and/or menthol), similar to tobacco.
• a carrier for example, polyhydric alcohol (e.g., glycerin, propylene glycol, etc.)]
• a flavoring agent for example, glycerin, propylene glycol, etc.
• the proportion of caryophyllene, etc. may be selected from the same range as above.
• the manner in which the composition of the present invention is used is not particularly limited, and includes, for example, a manner in which the composition is contained (adhered) to various parts of the filter (filter material, filter member), and the like.
• such a filter may be a filter containing a capsule (a filter incorporating a capsule, a filter configured with a filter member incorporating a capsule).
• such a filter includes a capsule (first capsule) containing the composition (caryophyllene, menthol, oil and fat) as a capsule.
• the capsule As the first capsule, the capsules described in the above section of capsules can be used.
• the capsule (first capsule) is composed of a core and a shell, and the core (contents) contains the composition of the present invention.
• it is a capsule containing the composition of the invention.
• Such a filter only needs to include at least a first capsule, and may include a second capsule different from the first capsule.
• the second capsule may be a capsule different from the first capsule, but for example, the second capsule may be a capsule containing contents different from the contents of the first capsule.
• Examples of such second capsules include capsules that are composed of a core and a shell, and the core (and shell) contains at least one of a carrier and a fragrance (in particular, does not contain caryophyllene).
• the capsules included in the above-mentioned filter can be those listed in the capsule section above, and capsules that do not contain caryophyllene (second capsules, etc.) are the ones listed in the capsule section above, except for the presence or absence of caryophyllene. You can use what is listed.
• the filter is not particularly limited, and may be, for example, a filter for cigarettes, inhalers, air conditioners, air cleaners, etc.
• filters containing capsules are suitable as cigarette filters, etc.
• caryophyllene (and menthol) can be efficiently ingested through the lungs.
• the number of capsules in a filter or the like can be selected as appropriate depending on its use, and may be one or two or more.
• the filter may be composed of only the first capsule (one type of capsule), or may further include a second capsule different from the first capsule.
• the number of first capsules and the number of second capsules may each be one, or two or more.
• respiratory disease refers to a disease, disorder or injury of the respiratory tract.
• the respiratory system consists of airways, which are air passageways, and alveoli, which are places for gas exchange.
• the respiratory tract consists of the nasal cavity, pharynx, laryngotrachea, and bronchi.
• respiratory diseases include chronic obstructive pulmonary disease (COPD), bronchitis, emphysema, interstitial pneumonia, bronchial asthma, and respiratory failure.
• COPD chronic obstructive pulmonary disease
• bronchitis bronchitis
• emphysema interstitial pneumonia
• bronchial asthma bronchial asthma
• respiratory failure chronic obstructive pulmonary disease (COPD)” is a lung disease caused by long-term inhalation exposure to harmful substances, mainly tobacco smoke, and shows airflow obstruction in respiratory function tests.
• Airflow obstruction refers to a condition where the airway cannot be exhaled smoothly during forced exhalation due to narrowing of the airway. Airflow obstruction occurs due to the combined involvement of peripheral airway lesions and emphysematous lesions in varying proportions. Clinically, the disease manifests as gradually progressing dyspnea on exertion, chronic cough, and sputum production, but these symptoms may be absent. Diagnosis requires that spirometry after inhalation of a bronchodilator shows a 1-second rate of less than 70%, and that other diseases that may cause airflow obstruction are excluded. Treatment methods include smoking cessation, drug therapy, and exercise therapy. Spirometry is a test that can measure the amount of air going in and out of the lungs, and is performed using, for example, a device called a spirometer.
• sleep improvement refers to an increase in non-REM sleep time, an increase in sleep time per day, and an increase in wakefulness the next morning, etc.
• sleep induction promotion refers to an increase in sleep onset latency. This refers to shortening, etc.
• fatigue reduction refers to improvement of unique discomfort, improvement of decline in physical activity ability accompanied by desire for rest, improvement of thinking ability, improvement of amount of activity, improvement of alertness, and improvement of muscle stiffness. ⁇ Includes improvements in tension and tension, promotion of blood flow, increase in vitality, relaxation, relaxation, and refreshment.
• improvement of complexion refers to improvement in skin color and luster.
• skin quality refers to the degree of intra-skin transparency, stratum corneum exfoliation, skin elasticity, and skin moisture retention
• skin quality improvement refers to improvement in these.
• Periodontal disease refers to a condition in which there is a disorder in the periodontal tissues that support the teeth, such as the gingiva, alveolar bone, cementum, or periodontal ligament. Examples include periodontitis. Periodontal disease is a lifestyle-related disease that affects approximately 80% of adults and is caused by bacterial infection.
• halitosis is a general term for all the bad odors of breath emitted from the mouth, and can range from those caused simply by smelly food left in the oral cavity to those caused by systemic diseases.
• the main components of bad breath include hydrogen sulfide, methyl mercaptan, and dimethyl disulfide, and these sulfur-containing compounds are said to be the main causes of bad breath.
• vitamin capacity refers to the amount of air when a person inhales air to the fullest and slowly exhales all of the air. Vital capacity can be measured, for example, with a device called a spirometer. When measured with a spirometer, vital capacity refers to the volume of air from maximum inspiration to maximum expiration. If your lung capacity is reduced, your lungs may become stiffer or your breathing muscles may become weaker, which may reduce the amount of air your lungs can take in. Diseases such as interstitial pneumonia, psychoidosis, pulmonary fibrosis, and pleurisy are suspected.
• 1 second rate refers to the rate at which you exhale in one second after you start exhaling when you inhale air to the fullest and exhale it all at once with maximum force. be.
• the rate per second can be measured, for example, with a device called a spirometer.
• 1-second rate refers to the ratio of 1-second volume to forced vital capacity.
• Forced vital capacity refers to the amount of air you can breathe in to your chest and exhale as much as possible.
• Volume in 1 second refers to the amount of air exhaled in the first second of forced vital capacity. It is normal for the rate per second to be 70% or more.
• Obstructive ventilation disorders include chronic obstructive pulmonary disease and bronchial asthma.
• the present invention will be explained in more detail with reference to Examples, but the present invention is not limited by these Examples.
• the examples herein have shown the adverse effects induced by nicotine intake, these effects are not limited to the adverse effects caused by nicotine intake.
• the therapeutic effect on respiratory diseases induced by other factors such as age, gender, passive smoking, and air pollution, the preventive effect on respiratory diseases, the sleep improvement effect on sleep disorders, insomnia, etc., and the sleep induction effect. Promoting effect, fatigue reducing effect on fatigue, etc., complexion improving effect on poor complexion, skin quality improving effect on rough skin, dry skin, etc., periodontal disease treatment effect on periodontal disease, etc., periodontal disease preventive effect, bad breath, etc. It can also be assumed that it has a bad breath suppression effect.
• smoking of cigarettes with ⁇ -caryophyllene-containing capsules provided in the filter has been cited as pulmonary ingestion of ⁇ -caryophyllene, but this is not limited to these, and as a result, - Any mode that allows caryophyllene to be ingested can be adopted. For example, it can be ingested through the lungs using an inhaler that inhales volatilized ⁇ -caryophyllene without burning it, or it can be ingested through the lungs by scattering ⁇ -caryophyllene into the space using an air freshener containing ⁇ -caryophyllene. included.
• oral intake also includes mixing ⁇ -caryophyllene with food or drink and taking it orally.
• the contents of capsules 1 to 4 were prepared.
• the weight of the contents of capsules 1 to 4 was 19.3 mg.
• Contents of capsule 1 MCT 100% by mass
• Contents of capsule 2 ⁇ -caryophyllene 5% by mass
• Contents of capsule 3 ⁇ -caryophyllene 15% by mass
• MCT 85% by mass Contents of capsule 4 ⁇ -caryophyllene 30% by mass
• ⁇ -caryophyllene in the capsule contents caryophyllene AKY-2348 (trade name: Rilak phyton (registered trademark)) manufactured by Inabata Fragrance Co., Ltd.
• capsules 1 to 4 thus prepared were filled into seamless capsules (easily disintegrating capsules) by a dropping method.
• the diameter of capsules 1 to 4 was 3.4 mm (shell thickness 50 ⁇ m, content liquid mass 19.3 mg).
• the formulation of the capsule shell was as follows. Gellan gum (Kelcogel; manufactured by CP Kelco) 35% by weight Pork gelatin (BCN250SC; manufactured by Nitta Gelatin) 55% by weight Reduced starch hydrolyzate (PO10; manufactured by Toa Kasei) 5% by weight Glycerin (food additive glycerin; manufactured by Sakamoto Pharmaceutical) 4.5% by weight Blue No. 1 (manufactured by Saneigen FFI) 0.5% by weight Furthermore, the breaking strength of Capsules 1 to 4 was 1530 g, and the breaking distance was 1.4 mm.
• Example 1 Preparation of capsule-containing cigarettes The four types of prepared capsules were inserted into the center of each of the following commercially available cigarette filters. Cigarettes using Capsule 1 (Comparative Examples 1-1 to 1-3) Tobacco using capsule 2 (Examples 1-1 to 1-5) Tobacco using capsule 3 (Examples 1-6 to 1-9) Tobacco using capsule 4 (Examples 1-10 to 1-12)
• Cigarettes using Capsule 1 (Comparative Examples 1-1 to 1-3) Cigarette 1: Lark Ultra 1mg KS Box (nicotine 0.1mg, tar 1mg) Cigarette 2: Winston Cabin Red 8 100's Box (nicotine 0.7mg, tar 8mg) Tobacco 3: Lark Super Mild 100's Box (nicotine 0.5mg, tar 6mg) Tobacco using capsule 2 (Examples 1-1 to 1-5) Cigarette 4: Marlboro Black Menthol 8 boxes (nicotine 0.6mg, tar 8mg) Tobacco 5: Lark Mild 100 Boxes (Nicotine 0.7mg, Tar 9mg) Tobacco 6: Natural American Spirit Organic Mint ONE (nicotine 0.1mg, tar 1mg) Tobacco 7: Marlboro Medium Box (0.7mg nicotine, 8mg tar) Tobacco 8: Highlight (nicotine 1.4mg, tar 17mg) Tobacco using
• the subjects' lung capacity and rate of 1 second were measured before starting a 12-week smoking experiment. Thereafter, each subject continued to smoke the number of cigarettes per day listed in Tables 1 to 4 for 12 weeks. Vital capacity and rate of 1 second were measured immediately before the start of the experiment (initial period), 4 weeks, 8 weeks, and 12 weeks after the start of the experiment, and the rate of change in these values from the start of the experiment was also calculated. The results obtained are shown in Tables 1 to 4.
• Table 5 shows the average and standard deviation of the vital capacity and rate of change in 1 second rate for the groups ingesting capsules 1 to 4 in Tables 1 to 4.
• the rate of change in vital capacity in the groups ingesting capsules 2 to 4 was higher than in the group ingesting capsule 1 (comparative examples 1-1 to 1-3). It was a good result. In this way, it has been found that by pressurizing and destroying caryophyllene-containing capsules and ingesting caryophyllene through the lungs, the decrease in lung capacity is more suppressed than when capsules that do not contain caryophyllene are used. In addition, as shown in Table 5, the rate per second of the groups taking capsules 2 to 4 (Examples 1-1 to 1-12) was higher than that of the group taking capsules 1 (comparative examples 1-1 to 1-3).
• the rate of change was better. In this way, it was found that by pressurizing and destroying caryophyllene-containing capsules and ingesting caryophyllene through the lungs, the decrease in rate per second was suppressed more than when using caryophyllene-free capsules.
• the mechanism of its effect on respiratory function is thought to be that ⁇ -caryophyllene suppresses inflammation in the lungs by acting on cannabinoid type 2 receptors (CB2 receptors) present in immune cells. From the above, it was found that ingesting ⁇ -caryophyllene while smoking suppresses the decline in vital capacity and rate of 1 second.
• Example 2 Pulmonary intake of ⁇ -caryophyllene (shortness of breath/difficulty breathing) Four types of capsules 1 to 4 were each inserted into the center of the following commercially available cigarette filters (Tables 6 to 9). Cigarettes using Capsule 1 (Comparative Examples 2-1 to 2-6) Tobacco using capsule 2 (Examples 2-1 to 2-7) Tobacco using capsule 3 (Examples 2-8 to 2-14) Tobacco using capsule 4 (Examples 2-15 to 2-21)
• the capsules in the filters of these cigarettes were pressurized to destroy them, the cigarettes were lit, and healthy subjects smoked the number of cigarettes listed in Tables 6 to 9 per day for 12 weeks.
• a questionnaire survey was conducted regarding shortness of breath and difficulty breathing during exercise. Specifically, a questionnaire survey was conducted before starting the 12-week smoking experiment, and then each subject continued to smoke the number of cigarettes per day listed in Tables 6 to 9 for 12 weeks. In this way, a questionnaire survey was conducted immediately before the start of the experiment (initial period), 4 weeks, 8 weeks, and 12 weeks after the start of the experiment.
• Scores are calculated using the value calculated by the evaluation score after the start of the experiment/initial evaluation score x 100, and when the start of the experiment is set as 100, the results of shortness of breath etc. after 4 weeks, 8 weeks, and 12 weeks. Scores were calculated based on the questionnaire results. The results obtained are shown in Table 10.
• ⁇ -caryophyllene suppresses inflammation in the lungs by acting on cannabinoid type 2 receptors (CB2 receptors) present in immune cells. It is believed that there is.
• Example 3 Pulmonary intake of ⁇ -caryophyllene (sleep quality) Four types of capsules 1 to 4 were each inserted into the center of the following commercially available cigarette filters (Tables 11 to 14). Cigarettes using Capsule 1 (Comparative Examples 3-1 to 3-6) Tobacco using capsule 2 (Examples 3-1 to 3-7) Tobacco using capsule 3 (Examples 3-8 to 3-14) Tobacco using capsule 4 (Examples 3-15 to 3-21)
• the capsules in the filters of these cigarettes were pressurized to destroy them, the cigarettes were lit, and healthy subjects smoked the number of cigarettes listed in Tables 11 to 14 per day for 12 weeks.
• a questionnaire survey regarding sleep quality was conducted immediately before the start of this study (initial period) and every 4 weeks. Specifically, a questionnaire survey was conducted before starting the 12-week smoking experiment, and then each subject continued to smoke the number of cigarettes per day listed in Tables 11 to 14 for 12 weeks. In this way, a questionnaire survey was conducted immediately before the start of the experiment (initial period), 4 weeks, 8 weeks, and 12 weeks after the start of the experiment.
• Example 4 Pulmonary intake of ⁇ -caryophyllene (falling asleep, feeling of fatigue, complexion, skin texture/firmness, swelling/bleeding of the gums)
• capsules 1 to 4 were each inserted into the center of the following commercially available cigarette filters (Tables 16 to 19).
• Cigarettes using Capsule 1 Comparative Examples 4-1 to 4-6
• Tobacco using capsule 2 Examples 4-1 to 4-7)
• Tobacco using capsule 3 Examples 4-8 to 4-14
• Examples 4-15 to 4-21 Tobacco using capsule 4 (Examples 4-15 to 4-21)
• ⁇ -caryophyllene acts on cannabinoid type 2 receptors (CB2 receptors) present in gum cells, suppresses matrix metalloprotease production in the gums, and promotes periodontal disease. It is thought that by improving the elastic function of teeth, periodontal disease can be treated or prevented.
• CB2 receptors cannabinoid type 2 receptors
• Example 5 Pulmonary intake of ⁇ -caryophyllene (bad breath) Four types of capsules 1 to 4 were each inserted into the center of the following commercially available cigarette filters (Tables 25 to 28). Cigarettes using Capsule 1 (Comparative Examples 5-1 to 5-6) Tobacco using capsule 2 (Examples 5-1 to 5-7) Tobacco using capsule 3 (Examples 5-8 to 5-14) Tobacco using capsule 4 (Examples 5-15 to 5-21)
• the capsules in the filters of these cigarettes were pressurized to destroy them, the cigarettes were lit, and healthy subjects smoked the number of cigarettes listed in Tables 25 to 28 per day for 12 weeks.
• a questionnaire survey was conducted regarding bad breath every four weeks. Specifically, before starting the 12-week smoking experiment, a questionnaire survey was conducted regarding bad breath, and then each subject continued to smoke the number of cigarettes per day listed in Tables 16 to 19 for 12 weeks. In this way, a questionnaire survey regarding bad breath was conducted immediately before the start of the experiment (initial period), 4 weeks, 8 weeks, and 12 weeks after the start of the experiment.
• the questionnaire asked the question, ⁇ Have you been concerned about bad breath after smoking lately?'' The responses were ⁇ concerned,'' ⁇ slightly concerned,'' ⁇ neutral,'' ⁇ not really bothered,'' and ⁇ not bothered.'' The evaluation points were set based on five answer options. ⁇ I don't care (5 points) ⁇ I don't really care (4 points) ⁇ Neither (3 points) ⁇ Somewhat concerned (2 points) ⁇ Curious (1 point)
• Capsules 5 and 6 were filled into soft capsules by a rotary method.
• the major axis, minor axis, and shell thickness of capsules 5 and 6 were as follows. Long diameter: 14.0mm Short diameter: 7.5mm Shell thickness: 1.0mm
• the formulation of the coating composition for capsules 5 and 6 was as follows: Starch 50% by weight Iota carrageenan 15% by weight Gum Arabic 1% by weight Glycerin 34% by weight Purified water (appropriate amount)
• the viscosity of the starch was 34 ⁇ 10 mPa ⁇ s.
• the method for measuring the viscosity of starch was as follows. No. 15 g of starch and 135 g of purified water were added to a 12 size bottle, mixed to sufficiently disperse the starch, and then heated in a 95° C. water bath for 90 minutes. At this time, stir every 10 minutes for the first 30 minutes and every 30 minutes thereafter. A spatula, a glass rod, or something similar thereto was used for stirring. Thereafter, the size liquid was cooled to 70° C., and the viscosity was measured. The viscosity was measured using a B-type viscometer (Brookfield DV-E, liquid temperature 70°C, rotor No. 2, after rotating for 1 minute at 100 rpm) using the obtained 10% paste liquid. .
• the viscosity of the iota carrageenan was 2,600 ⁇ 800 mPa ⁇ s.
• the method for measuring the viscosity of iota carrageenan was as follows. No. 5 g of iota carrageenan and 12 g of glycerin were added to a 12 size bottle and mixed well with a spatula, and then 103 g of purified water was added and mixed well. The prepared liquid mixture was heated in a 95°C water bath for 90 minutes. At that time, the mixture was stirred every 10 minutes for the first 30 minutes and every 30 minutes thereafter. Thereafter, the mixed liquid was cooled to 70°C, and the viscosity was measured. The viscosity was measured using a B-type viscometer (Brookfield DV-E, liquid temperature 70°C, rotor No. 3, after rotating for 1 minute at 12 rpm) using the obtained 4% mixed liquid. .
• the viscosity of the gum arabic was 260 ⁇ 80 mPa ⁇ s.
• the method for measuring the viscosity of gum arabic was as follows. 25 g of gum arabic and 75 g of purified water were placed in a beaker and mixed well with a stirrer. The prepared mixed solution was transferred to No. After transferring the mixture to a 12-standard bottle and adjusting the temperature of the mixture to 25°C, the viscosity was measured. The viscosity was measured using a B-type viscometer (Brookfield DV-E, liquid temperature 25°C, rotor No. 2, after rotating for 1 minute at 60 rpm) using the obtained 25% mixed liquid. .
• Capsules 5 and 6 were manufactured using the above-described content liquid composition and film composition using a rotary die filling machine for soft capsules. Specifically, in a rotary die-type filling machine, the stored coating liquid was poured into a spreader box through a supply hose, and from there was cast by gravity drop onto a casting drum, where it was cooled in the drum. In this way, a coating film that was to be used as the material for the coatings (shells) of Capsules 5 and 6 was produced by utilizing the sol-gel transition property of the coating composition. The coating film was stripped from the drum and fed over rollers to a mold on two rolls.
• the two films are reheated by the segment and the filler is injected at the same time.
• the inner liquid composition is filled and sealed using heat sealing while being punched out. Ta.
• the net of the coated film after being punched out is pulled by rollers located at the bottom of the filling machine, giving appropriate tension to the coated film.
• the punched, undried capsules were then fed to a dryer, and completed capsules 5 and 6 were manufactured through a drying process).
• Example 6 Oral intake of ⁇ -caryophyllene (shortness of breath/difficulty breathing, quality of sleep, falling asleep, feeling of fatigue, skin texture/firmness, swelling/bleeding of the gums, bad breath) Two types of capsules 5 and 6 were each orally ingested by healthy subjects, one capsule each twice a day. Immediately before the start of this study (initial stage) and one week later, a questionnaire survey was conducted regarding shortness of breath and breathlessness during exercise, quality of sleep, falling asleep, feeling of fatigue, skin texture and firmness, swelling and bleeding of the gums, and bad breath. went. The questionnaire for each of these items was conducted in the same manner as in Examples 2-5.
• Example 6-1 the group taking Capsule 6 (Example 6-1) had better scores in the questionnaire regarding shortness of breath, etc., than the group taking Capsule 5 (Comparative Example 6-1).
• orally ingesting caryophyllene suppressed shortness of breath and breathlessness more than when using capsules that did not contain caryophyllene.
• ⁇ -caryophyllene suppresses inflammation in the lungs by acting on cannabinoid type 2 receptors (CB2 receptors) present in immune cells. It is believed that there is.
• Example 6-2 the group taking Capsule 6 (Example 6-2) had better scores in the questionnaire regarding sleep quality than the group taking Capsule 5 (Comparative Example 6-2). In this way, it was found that orally ingesting caryophyllene improves sleep quality. These results indicate that ingestion of caryophyllene has the effect of improving sleep and promoting sleep induction. The mechanism of its effect on sleep quality is thought to be that ⁇ -caryophyllene acts on cannabinoid type 2 receptors (CB2 receptors) present in the brain.
• CB2 receptors cannabinoid type 2 receptors

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