Cannabidiol-containing seamless soft capsules

Abstract

The present invention addresses the problem of improving the intake efficiency of cannabidiol (CBD). This problem can be solved by a seamless soft capsule that comprises a capsule coating film and contents enclosed in the capsule coating film, wherein the contents contain CBD.

Description

Technical Field

[0001] The present invention relates to a cannabidiol-containing seamless soft capsule.

Background Art

[0002] Marijuana contains various chemical substances, which are collectively referred to as cannabinoids. Examples of the chemical substances contained in cannabinoids include tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinchromene (CBC), cannabinergonic acid (CBE), cannabigerol (CBG), cannabinol (CBN), and cannabidiovaleric acid (CBDV).

[0003] In the Cannabis Control Law of Japan, the components of the roots, leaves, and flower spikes of marijuana are subject to regulation, while the components of seeds and mature stems are not. CBD, which is one type of cannabinoid, is contained in the seeds and mature stems of marijuana and has been reported to have useful effects. For example, CBD is expected to be used for symptoms and diseases such as stress, insomnia, schizophrenia, depression, atopic dermatitis, eating disorders (anorexia nervosa), epilepsy, drug dependence, alcohol dependence, obsessive-compulsive disorder, Parkinson's disease, cataract, glaucoma, Huntington's disease, amyotrophic lateral sclerosis (ALS), stroke, heart disease, liver disease, traumatic brain injury, hypertension, cell inflammation, constipation, cancer, brain tumor, acquired immunodeficiency syndrome (AIDS), autoimmune uveitis, fibromyalgia, osteoporosis, etc. In addition, the World Health Organization (WHO) evaluated the safety of CBD in June 2018 and advised that it does not fall under the category of drugs in the International Narcotics Control Board.

[0004] Products containing CBD already exist. For example, there are foods, e-cigarettes, skin care products, refreshment oils, and bath care products containing CBD. In addition, various dosage forms containing CBD are known (for example, Patent Documents 1 to 5).

Prior Art Documents

Patent Documents

[0005] [Patent Document 1] Special Publication No. 2018-505912 [Patent Document 2] Special Publication No. 2019-518760 [Patent Document 3] Special Publication No. 2019-523775 [Patent Document 4] Patent No. 4467883 [Patent Document 5] Patent No. 4920588 [Overview of the project] [Problems that the invention aims to solve]

[0006] The present invention aims to improve the efficiency of CBD intake. [Means for solving the problem]

[0007] As a result of diligent research by the inventors, it was discovered that the efficiency of CBD intake can be improved by encapsulating CBD in a capsule coating to create a seamless soft capsule.

[0008] The present invention includes the following embodiments. [1] Capsule coating and The contents enclosed in the aforementioned capsule membrane, Includes, Seamless soft capsules containing cannabidiol. [2] A seamless soft capsule described in [1] that is rapidly dissolving in the oral cavity. [3] A seamless soft capsule described in [1] that is easily ruptured in the oral cavity. [4] A seamless soft capsule according to any one of [1] to [3], wherein the thickness of the capsule coating is 10 to 900 μm. [5] The seamless soft capsule according to [4], wherein the thickness of the capsule coating is 10 to 200 μm. [6] The seamless soft capsule according to any one of [1] to [5], wherein the coating rate of the seamless soft capsule is 3 to 50%. [7] The seamless soft capsule according to any one of [1] to [6], wherein the diameter of the seamless soft capsule is 1 to 20 mm. [8] A seamless soft capsule according to any one of [1] to [7], wherein the contents consist solely of cannabidiol as a cannabinoid. [9] Container and A seamless soft capsule according to any of [1] to [8] placed in the container described above, Includes, A product in which only cannabidiol is listed as a cannabinoid among the ingredients of the aforementioned seamless soft capsules. [Effects of the Invention]

[0009] According to the present invention, the efficiency of CBD intake can be improved. [Modes for carrying out the invention]

[0010] The embodiments of the present invention will be described in detail below, but the present invention is not limited to these, and various modifications are possible without departing from the spirit of the invention.

[0011] <Seamless Soft Capsules> One embodiment of the present invention relates to a seamless soft capsule comprising a capsule shell and contents enclosed within the capsule shell (hereinafter referred to as "capsule contents"), wherein the contents contain cannabidiol (CBD). Surprisingly, the seamless soft capsule according to this embodiment can improve the stability of CBD and improve the efficiency of CBD intake.

[0012] The following reasons may be considered for the improved stability of CBD, but the present invention is not limited thereto. CBD is presumed to tend to decompose when air and light coexist. However, when CBD is made into seamless soft capsules, as understood from its manufacturing method (the dropping method described later), since there is no air inside the capsule film, at least air can be excluded. It is considered that this can suppress the decomposition of CBD.

[0013] [Capsule film] The capsule film contains a base material (hereinafter referred to as "capsule film base material"). The capsule film base material is what remains after removing water, plasticizers, and additives from the components constituting the capsule film. Examples of the capsule film base material include gelatin and polysaccharides (such as carrageenan, gellan gum, pectin, alginates, soluble starches (starches made water-soluble by chemical or physical treatment), agar, etc.). Regarding soluble starches, examples of chemical treatment include chemical modification with hydroxypropyl groups, etc. Examples of physical treatment include oxidation treatment, wet heat treatment in the presence of salts, ultrasonic treatment, and hydrothermal heating. The capsule film base material may be used alone or in combination of two or more. Although not particularly limited, gelatin, or carrageenan and soluble starches may be used as the capsule film base material. As gelatin, gelatin derived from pigskin, bovine bone, cowhide, fish scales, etc. can be used.

[0014] The lower limit of the amount of the capsule film base material may be, for example, 20% by mass, 30% by mass, 40% by mass, 50% by mass, 60% by mass, 70% by mass or 80% by mass based on the total mass of all components (solid components excluding water) constituting the capsule film. The upper limit of the amount of the capsule film base material may be, for example, 100% by mass, 90% by mass, 80% by mass, 70% by mass or 60% by mass based on the total mass of all components constituting the capsule film. A numerical range may be defined by appropriately combining the lower limit and the upper limit of the amount of the capsule film base material. For example, the amount of the capsule film base material may be 20 - 100% by mass, 20 - 90% by mass, 20 - 80% by mass, 20 - 70% by mass, 20 - 60% by mass, 30 - 100% by mass, 30 - 90% by mass, 30 - 80% by mass, 30 - 70% by mass, 30 - 60% by mass, 40 - 100% by mass, 40 - 90% by mass, 40 - 80% by mass, 40 - 70% by mass, 40 - 60% by mass, 50 - 90% by mass, 50 - 80% by mass, 50 - 70% by mass, 50 - 60% by mass, 60 - 90% by mass, 60 - 80% by mass, 60 - 70% by mass, 70 - 90% by mass, 70 - 80% by mass or 80 - 90% by mass based on the total mass of all components constituting the capsule film.

[0015] In addition to the capsule film base material, the capsule film may further contain a plasticizer. Examples of the plasticizer include polyhydric alcohols (such as glycerin, polyethylene glycol, propylene glycol, polypropylene glycol, etc.), monosaccharides (such as glucose, fructose, glucopyranose, galactose, etc.), disaccharides or oligosaccharides (such as sucrose, maltose, trehalose, coupling sugar, etc.), polysaccharides (such as pullulan, gum arabic, arabinogalactan, cellulose, etc.), and sugar alcohols (such as erythritol, xylitol, sorbitol, maltitol, lactitol, palatinite, mannitol, galactitol, etc.). The plasticizer may be used alone or in combination of two or more. Although not particularly limited, glycerin, sorbitol and maltitol may be used as the plasticizer.

[0016] The lower limit of the amount of plasticizer may be, for example, 10% by mass, 20% by mass, 30% by mass, or 40% by mass, based on the total mass of all components constituting the capsule coating. The upper limit of the amount of plasticizer may be, for example, 60% by mass, 50% by mass, 40% by mass, 30% by mass, or 20% by mass, based on the total mass of all components constituting the capsule coating. The numerical range may be defined by appropriately combining the aforementioned lower and upper limits of the amount of plasticizer. For example, the amount of plasticizer may be 10-60% by mass, 10-50% by mass, 10-40% by mass, 10-30% by mass, 10-20% by mass, 20-60% by mass, 20-50% by mass, 20-40% by mass, 20-30% by mass, 30-60% by mass, 30-50% by mass, 30-40% by mass, 40-60% by mass, or 40-50% by mass, based on the total mass of all components constituting the capsule coating.

[0017] The capsule coating may further contain additives. Examples of additives include dyes, light-shielding agents, sweeteners, flavorings, preservatives, starches (that have not undergone chemical or physical treatment), celluloses, pH adjusters, and neutralizing agents. Examples of dyes include natural or synthetic dyes. Examples of light-shielding agents include titanium dioxide, which is a dye that whitens the capsule coating, and water-insoluble powders (such as starches that have not undergone chemical or physical treatment, celluloses, or insoluble calcium) that give the capsule coating a frosted appearance.

[0018] [Capsule contents] The capsule contents contain cannabidiol (CBD) as the active ingredient. CBD may be derived from plants or chemically synthesized. Examples of plants include hemp, cannabis, citrus fruits, and hops.

[0019] The lower limit of the amount of CBD may be, for example, 1% by mass, 3% by mass, 5% by mass, 10% by mass, 20% by mass, 30% by mass, 40% by mass, 50% by mass, 60% by mass, 70% by mass, 80% by mass, or 90% by mass, based on the mass of the capsule contents. The upper limit of the amount of CBD may be, for example, 100% by mass, 90% by mass, 80% by mass, 70% by mass, 60% by mass, 50% by mass, 40% by mass, 30% by mass, 20% by mass, 10% by mass, or 5% by mass, based on the mass of the capsule contents. The numerical range of the amount of CBD may be defined by appropriately combining the aforementioned lower and upper limits. For example, the amount of CBD, based on the mass of the capsule contents, is 1-100% by mass, 1-90% by mass, 1-80% by mass, 1-70% by mass, 1-60% by mass, 1-50% by mass, 1-40% by mass, 1-30% by mass, 1-20% by mass, 1-10% by mass, 1-5% by mass, 3-100% by mass, 3-90% by mass, 3-80% by mass, 3-70% by mass, 3-60% by mass, 3-50% by mass, 3-40% by mass, 3-3 0% by mass, 3-20% by mass, 3-10% by mass, 3-5% by mass, 5-100% by mass, 5-90% by mass, 5-80% by mass, 5-70% by mass, 5-60% by mass, 5-50% by mass, 5-40% by mass, 5-3 0% by mass, 5-20% by mass, 5-10% by mass, 10-100% by mass, 10-90% by mass, 10-80% by mass, 10-70% by mass, 10-60% by mass, 10-50% by mass, 10-40% by mass, 10- 30% by mass, 10-20% by mass, 20-100% by mass, 20-90% by mass, 20-80% by mass, 20-70% by mass, 20-60% by mass, 20-50% by mass, 20-40% by mass, 20-30% by mass, 30-100% by mass, 30-90% by mass, 30-80% by mass, 30-70% by mass, 30-60% by mass, 30-50% by mass, 30-40% by mass, 40-100% by mass, 40-90% by mass, 40-80 Mass%, 40-70 mass%, 40-60 mass%, 40-50 mass%, 50-100 mass%, 50-90 mass%, 50-80 mass%, 50-70 mass%, 50-60 mass%, 60-100 mass%, 6 It may be 0-90% by mass, 60-80% by mass, 60-70% by mass, 70-100% by mass, 70-90% by mass, 70-80% by mass, 80-100% by mass, 80-90% by mass, or 90-100% by mass.

[0020] Capsule contents can take the form of, for example, a solution, a dispersion, or a paste. A solution-type capsule contents can be prepared by dissolving CBD in a CBD-dissolving solution. A dispersion-type capsule contents can be prepared by dispersing CBD together with an emulsifier in a solution that does not dissolve CBD or dissolves it poorly. A paste-type capsule contents can be prepared by heating and dissolving a thickener, hydrogenated oil, and waxes in a liquid oil, stirring, cooling, and defoaming to obtain a paste base, to which CBD is added and homogenized.

[0021] The capsule contents may contain additional active ingredients (hereinafter referred to as "second active ingredients") in addition to CBD. In this specification, "active ingredients" means ingredients that exert the effects, functions, and usefulness indicated, advertised, or suggested in relation to products including seamless soft capsules. The second active ingredient may be one type or a combination of two or more types. Examples of second active ingredients include cannabinoids other than CBD. Examples of such cannabinoids include tetrahydrocannabinol (THC), cannabichromene (CBC), cannabiersoin (CBE), cannabigerol (CBG), cannabinol (CBN), and cannabidivarin (CBDV). As an example, the capsule contents may contain CBD and THC.

[0022] The contents of the capsule may contain only CBD and other cannabinoids as active ingredients. The capsule contents may contain only CBD as the active ingredient. The capsule contents may contain CBD as the active ingredient, but may not contain any other cannabinoids. The capsule contents may contain CBD as the active ingredient, but do not necessarily have to contain THC. The capsule contents may contain CBD as the active ingredient, but do not necessarily need to contain terpenes. The contents of the capsule may contain only CBD as the cannabinoid. The contents of the capsule do not need to contain THC. The contents of the capsule do not need to contain terpenes. Whether or not a product contains "CBD only as a cannabinoid" is determined based on the manufacturing date of the seamless soft capsule. In other words, even if other cannabinoids are produced over time, if the seamless soft capsule contained only CBD as a cannabinoid at the time of manufacturing, it will be considered to contain "CBD only as a cannabinoid."

[0023] If the capsule contents contain a second active ingredient, the lower limit of the amount of CBD may be, for example, 1% by mass, 5% by mass, 10% by mass, 20% by mass, 30% by mass, 40% by mass, 50% by mass, 60% by mass, 70% by mass, or 80% by mass, based on the total mass of all active ingredients. The upper limit of the amount of CBD may be, for example, 95% by mass, 90% by mass, 80% by mass, 70% by mass, or 60% by mass, based on the total mass of all active ingredients. The numerical range of the amount of CBD may be defined by appropriately combining the aforementioned lower and upper limits. For example, the amount of CBD, based on the total mass of all active ingredients, is 1-95% by mass, 1-90% by mass, 1-80% by mass, 1-70% by mass, 1-60% by mass, 5-95% by mass, 5-90% by mass, 5-80% by mass, 5-70% by mass, 5-60% by mass, 10-95% by mass, 10-90% by mass, 10-80% by mass, 10-70% by mass, 10-60% by mass, 20-95% by mass, 20-90% by mass, 20-80% by mass, 20-70% by mass, 20-60% by mass, 30-95% by mass, 30 ~90% by mass, 30-80% by mass, 30-70% by mass, 30-60% by mass, 40-95% by mass, 40-90% by mass, 40-80% by mass, 40-70% by mass, 40-60% by mass, 50-95% by mass, 50-90% by mass, 50-80% by mass, It may be 50-70% by mass, 50-60% by mass, 60-95% by mass, 60-90% by mass, 60-80% by mass, 60-70% by mass, 70-95% by mass, 70-90% by mass, 70-80% by mass, 80-95% by mass, or 80-90% by mass.

[0024] The contents of the capsule may contain additional ingredients in addition to the active ingredient. Examples of such ingredients include oils and fats, waxes, hydrogenated oils, mineral oils, fatty acids, stimulants, sweeteners, and flavorings.

[0025] Examples of oils and fats include avocado oil, almond oil, flaxseed oil, fennel oil, perilla oil, olive oil, olive squalene, orange oil, orange raffia oil, sesame oil, garlic oil, cocoa butter, pumpkin seed oil, chamomile oil, carrot oil, cucumber oil, beef tallow fatty acid, kukui nut oil, cranberry seed oil, brown rice germ oil, rice oil, wheat germ oil, safflower oil, shea butter, liquid shea butter, shiso oil, soybean oil, evening primrose oil, camellia oil, corn oil, and na Examples include seed oils, saw palmetto extract oil, Job's tears oil, peach kernel oil, parsley seed oil, castor oil, sunflower oil, grape seed oil, borage oil, macadamia nut oil, meadowhome oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg yolk oil, fish oil, palm oil, palm kernel oil, Japan wax, coconut oil, long-chain, medium-chain, and short-chain fatty acid triglycerides, diacylglycerides, beef tallow, lard, squalene, squalane, pristane, and hydrogenated versions of these oils and fats.

[0026] Examples of waxes and waxes include shellac wax, beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, cyclic lanolin, lanolin wax, candelilla wax, Japanese wax, montan wax, shellac wax, and rice wax.

[0027] Examples of hardened oils include hydrogenated vegetable oils (hydrogenated vegetable oils), hardened beef tallow, and hardened lard.

[0028] Examples of mineral oils include liquid paraffin, petrolatum, paraffin, ozokeride, ceresin, and microcrystalline wax.

[0029] Examples of fatty acids include natural fatty acids (lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, conjugated linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, 12-hydroxystearic acid, undecylenic acid, tall oil, lanolinic acid, etc.) and synthetic fatty acids (isononanoic acid, caproic acid, 2-ethylbutanoic acid, isopentanoic acid, 2-methylpentanoic acid, 2-ethylhexanoic acid, isopentanoic acid, etc.).

[0030] Examples of stimulants include capsicum tincture, capsicum oil, nonylic acid vanillamide, cantharis tincture, ginger tincture, ginger oil, peppermint oil, l-menthol, camphor, and benzyl nicotinate.

[0031] Examples of sweeteners include sucrose, stevia, glycyrrhizin, monk fruit, thaumatin, saccharin, aspartame, acesulfame potassium, sucralose, erythritol, xylitol, sorbitol, palatinitol, maltitol, lactitol, and mannitol.

[0032] Examples of flavorings include fruit flavorings (lemon flavoring, orange flavoring, grape flavoring, etc.), mint flavoring, and menthol flavoring.

[0033] The contents of the capsule may contain emulsifiers to maintain the uniformity of each component and improve absorption in the body, but they do not necessarily have to contain emulsifiers. The contents of the capsule may contain an emulsifier to improve absorption in the body, but it does not have to contain an emulsifier. The capsule contents may contain glyceryl monooleate and / or glyceryl monostearate to maintain the uniformity of each component and to improve absorption in the body, but may not contain glyceryl monooleate and / or glyceryl monostearate.

[0034] [Seamless Soft Capsules] The lower limit of the diameter of the spherical seamless soft capsule may be, for example, 1 mm, 3 mm, 5 mm, or 10 mm. The upper limit of the diameter of the seamless soft capsule may be, for example, 20 mm, 15 mm, 10 mm, or 5 mm. The numerical range may be defined by appropriately combining the lower and upper limits of the diameter of the seamless soft capsule. For example, the diameter of the seamless soft capsule may be 1-20 mm, 1-15 mm, 1-10 mm, 1-5 mm, 3-20 mm, 3-15 mm, 3-10 mm, 3-5 mm, 5-20 mm, 5-15 mm, 5-10 mm, 10-20 mm, or 10-15 mm.

[0035] Seamless soft capsules may have a frosted surface or a glossy surface. A frosted surface can be formed, for example, by adding a water-insoluble powder (such as starches, celluloses, or water-soluble calcium that have not undergone chemical or physical treatment) as a capsule coating component, or by adding an excess of a crystalline powder such as erythritol as a capsule coating component and drying the capsule coating to precipitate crystals.

[0036] The capsule coating of a seamless soft capsule may be transparent or colored. If the capsule coating is colored, the color may be, for example, brown. A colored capsule coating can be formed, for example, by adding a dye or a light-shielding agent as a component of the capsule coating.

[0037] The lower limit of the capsule coating thickness of a seamless soft capsule may be, for example, 10 μm, 20 μm, 50 μm, 100 μm, or 200 μm. The upper limit of the capsule coating thickness may be, for example, 900 μm, 600 μm, 400 μm, 200 μm, 170 μm, or 130 μm. The numerical range may be defined by appropriately combining the lower and upper limits of the capsule coating thickness. For example, the capsule coating thickness may be defined as follows: 10-900 μm, 10-600 μm, 10-400 μm, 10-200 μm, 10-170 μm, 10-130 μm, 20-900 μm, 20-600 μm, 20-400 μm, 20-200 μm, 20-170 μm, 20-130 μm, 50-900 μm, 50-60 The measurement range may be 0 μm, 50-400 μm, 50-200 μm, 50-170 μm, 50-130 μm, 100-900 μm, 100-600 μm, 100-400 μm, 100-200 μm, 100-170 μm, 100-130 μm, 200-900 μm, 200-600 μm, or 200-400 μm. If the capsule coating thickness differs depending on the part of the seamless soft capsule, the measurement should be taken at the part where the capsule coating thickness is maximum. The method for measuring the capsule coating thickness is as described in the examples.

[0038] The lower limit of the coating rate for seamless soft capsules may be, for example, 3%, 4%, 8%, 12%, or 16%. The upper limit of the coating rate may be, for example, 50%, 40%, 30%, 20%, 18%, 16%, 14%, or 12%. The numerical range may be defined by appropriately combining the aforementioned lower and upper limits of the coating rate. For example, the coating percentage may be set to 3-50%, 3-40%, 3-30%, 3-20%, 3-18%, 3-16%, 3-14%, 3-12%, 4-50%, 4-40%, 4-30%, 4-20%, 4-18%, 4-16%, 4-14%, 4-12%, 8-50%, 8-40%, 8-30%, 8-20%, 8-18%, 8-16%, 8-14%, 8-12%, 12-50%, 12-40%, 12-30%, 12-20%, 12-18%, 12-16%, 12-14%, 16-50%, 16-40%, 16-30%, 16-20%, or 16-18%. In this specification, "coating ratio" refers to the ratio of the mass of the capsule coating to the mass of the seamless soft capsule. The method for measuring the coating ratio is as described in the examples.

[0039] Preferably, the internal space of the seamless soft capsule, formed by the capsule coating, is completely filled with the capsule contents. In this specification, "completely filled" means that the capsule contents are filled so that there are no gaps (no gas) between the inner surface of the capsule coating and the capsule contents.

[0040] When seamless soft capsules are exposed to light with a total illuminance of 1.2 million lux·hr, the remaining CBD content is preferably 80% or more, more preferably 90% or more, even more preferably 95% or more, and particularly preferably 98% or more. The light irradiation conditions are as described in the examples.

[0041] Seamless soft capsules may be designed for sublingual administration. Sublingual administration offers superior bioavailability, thus improving the efficiency of CBD intake.

[0042] Seamless soft capsules may also be orally disintegrating. In this specification, "orally disintegrating" means that the disintegration time measured with an oral disintegration tester is 60 seconds or less. Specifically, using a tricorp tester (manufactured by Okada Seikou Co., Ltd.), a seamless soft capsule is placed between upper and lower metal meshes, and artificial saliva is dropped onto the upper mesh while applying pressure. The time it takes for the seamless soft capsule to disintegrate and for the upper and lower meshes to come into contact is defined as the disintegration time. The measurement conditions are as follows. Load: 40g Artificial saliva (KCl:1.47g / L, NaCl:1.44g / L, Tween80:0.3%) Liquid temperature: 37℃ Dripping speed: 6mL / min

[0043] Seamless soft capsules may be easily ruptured in the oral cavity. In this specification, "easily ruptured in the oral cavity" means that the contents can be easily released by chewing or other means in the oral cavity.

[0044] Examples of administration routes for seamless soft capsules include sublingual administration and oral administration. While not particularly limited, sublingual administration is preferred.

[0045] Seamless soft capsules can be used, for example, as pharmaceuticals, quasi-drugs, or foods. Examples of foods include general foods and functional foods (foods for specified health uses, foods with functional claims, foods with nutritional function claims, etc.).

[0046] Symptoms and diseases that can be treated with seamless soft capsules include, for example, stress, insomnia, schizophrenia, depression, atopic dermatitis, eating disorders (anorexia nervosa), epilepsy, drug addiction, alcoholism, obsessive-compulsive disorder, Parkinson's disease, cataracts, glaucoma, Huntington's disease, amyotrophic lateral sclerosis (ALS), stroke, heart disease, liver disease, traumatic brain injury, hypertension, cellular inflammation, constipation, cancer, brain tumors, acquired immunodeficiency syndrome (AIDS), autoimmune uveitis, fibromyalgia, and osteoporosis.

[0047] (Seamless soft capsule A) One embodiment of a seamless soft capsule is a seamless soft capsule (hereinafter referred to as "seamless soft capsule A") that includes a capsule coating (hereinafter referred to as "capsule coating A") containing carrageenan, an acidic pH adjuster, and a neutralizing agent. By including these components, it is possible to create a capsule coating that is easily breakable while maintaining hardness. Making the capsule coating easily breakable has advantages, such as facilitating sublingual administration.

[0048] Capsule coating A can be prepared by a process in which carrageenan is decomposed with an acidic pH adjuster and the decomposition is stopped with a neutralizing agent. By adjusting the degree of decomposition, an appropriate viscosity can be achieved. The viscosity may be adjusted, for example, to 30-150 mPa·s or 50-100 mPa·s. The viscosity can be measured using a C-type viscometer, model CVR-20, manufactured by Tokimec Co., Ltd., at a liquid temperature of 75°C. Rotor No. 0 can be used when the viscosity is 100 mPa·s or less, and rotor No. 1 can be used when the viscosity exceeds 100 mPa·s.

[0049] Examples of carrageenan used in capsule coating A include κ-carrageenan, ι-carrageenan, and λ-carrageenan. While not particularly limited, κ-carrageenan is preferred.

[0050] The amount of carrageenan in capsule coating A may be, for example, 50% or more or 70% or more of the total mass of all components constituting the capsule coating.

[0051] Examples of acidic pH adjusting agents in capsule coating A include citric acid, malic acid, acetic acid, formic acid, oxalic acid, lactic acid, phytic acid, and hydrochloric acid.

[0052] Examples of neutralizing agents for capsule coating A include alkalis such as disodium hydrogen phosphate, sodium citrate, and sodium bicarbonate.

[0053] The diameter of the seamless soft capsule A may be, for example, 0.5 to 15 mm or 1 to 8 mm.

[0054] The thickness of the capsule coating A may be, for example, 40 μm or less or 30 μm or less.

[0055] The coating percentage of capsule coating A may be, for example, 5-20% or 7-15%.

[0056] Capsule coating A may further contain, for example, plasticizers, alginates, sugars, dextrins, starch, or modified starch.

[0057] (Seamless Soft Capsule B) One embodiment of a seamless soft capsule is a seamless soft capsule (hereinafter referred to as "seamless soft capsule B") that includes a capsule coating (hereinafter referred to as "capsule coating B") containing sorbitol, maltitol, and glycerin as plasticizers. By including these components in predetermined amounts, a capsule coating with excellent flexibility can be obtained.

[0058] When the main component of the capsule coating material is gelatin, it is preferable that the amount of sorbitol be 1 to 15 parts by mass, maltitol be 1 to 30 parts by mass, and glycerin be 40 to 60 parts by mass per 100 parts by mass of gelatin.

[0059] When the main component of the capsule coating substrate is a mixture of starches and carrageenan, it is preferable that the amount of sorbitol be 1 to 15 parts by mass, maltitol be 1 to 30 parts by mass, and glycerin be 30 to 60 parts by mass per 100 parts by mass of the mixture.

[0060] Examples of carrageenans used in capsule coating A include κ-carrageenan and ι-carrageenan.

[0061] Examples of starches used in capsule coating A include oxidized starch, starch dispersion, moist heat-treated starch, and acid-treated starch.

[0062] <Product> One embodiment of the present invention relates to a product comprising a container and the seamless soft capsule placed in the container. The shape, material, etc., of the container are not particularly limited, and it is sufficient if it is capable of containing the seamless soft capsule.

[0063] Only CBD and other cannabinoids may be listed as ingredients in seamless soft capsules. CBD alone may be listed as the active ingredient in the seamless soft capsules. CBD may be listed as the active ingredient in the seamless soft capsules, and other cannabinoids may not be listed. CBD may be listed as the active ingredient in the seamless soft capsules, and THC may not be listed. The active ingredient CBD may be listed on the product as an ingredient in seamless soft capsules, and terpenes do not need to be listed. CBD alone may be listed as the ingredient in a seamless soft capsule product. THC does not need to be listed as an ingredient in the seamless soft capsule product. Terpenes do not need to be listed on the product as an ingredient in seamless soft capsules. Examples of product labeling include markings on the container, instruction manual, or packaging.

[0064] <Method for manufacturing seamless soft capsules> The method for manufacturing seamless soft capsules is not particularly limited, and known methods can be used. For example, a method for manufacturing seamless soft capsules is the dropper method (including the liquid dropper method, in which a double droplet is discharged while a concentric double nozzle is immersed in a carrier liquid, and the air dropper method, in which droplets are discharged into the air while a concentric double nozzle is suspended above the carrier liquid).

[0065] The size of a seamless soft capsule can be adjusted, for example, by changing the size of the nozzle used to dispense the capsule coating liquid and capsule contents in a dropper dispensing method.

[0066] The thickness and coating ratio of the capsule coating can be adjusted, for example, by changing the size of the nozzle through which the capsule coating solution passes in the dropper method. [Examples]

[0067] The present invention will be described in more detail below using examples and comparative examples, but the technical scope of the present invention is not limited thereto.

[0068] <Measurement method> [coating thickness] The capsule coating thickness was measured using a high-resolution 3D X-ray microscope, "nano3DX" (manufactured by Rigaku Corporation). This device allows for non-destructive observation of cross-sectional conditions, where differences in density are reflected as contrast in the image. A molybdenum target was used as the X-ray source, with a lens magnification of 1.25x, a pixel size of 0.7 μm / voxel, an exposure time of 8 seconds, and 400 cross-sections. The center (equator plane) of the capsule was analyzed and imaged. The coating thickness was measured at four locations (top, bottom, left, and right) for each capsule, and the average value was taken as the coating thickness of that capsule. The average of three capsules was then taken.

[0069] [Coating rate] The coating ratio was defined as the ratio of the capsule coating mass to the total capsule mass. Each mass was measured using a standard electronic balance.

[0070] [Size of seamless soft capsules] The diameter of the seamless soft capsule was measured using calipers.

[0071] <Manufacturing Example 1> [Manufacturing of seamless soft capsules] (1) Preparation of capsule coating solution Gelatin (10 kg), glycerin (5.0 kg), erythritol (2.0 kg), xylitol (0.5 kg), and water (50.0 kg) were mixed and stirred while heating until the gelatin dissolved. The mixture was then sieved through a 100-mesh sieve to prepare the capsule coating solution.

[0072] (2) Preparation of capsule contents 10% CBD oil (2.5 kg), consisting of CBD (10%) and organic hemp oil (90%), rapeseed salad oil (2.25 kg), and l-menthol (0.25 kg) were mixed and stirred until the l-menthol dissolved. The mixture was then sieved through a 100-mesh sieve to prepare the capsule contents.

[0073] (3) Manufacturing of seamless soft capsules Seamless soft capsules were formed by a dropper method using the aforementioned capsule coating solution and capsule contents. Specifically, the capsule coating solution was dropped from the outer nozzle of a concentric double nozzle, and the capsule contents from the inner nozzle, into cooled MCT oil (medium-chain triglyceride), forming capsules with a content of 200 mg in which the internal space of the capsule was completely filled with the contents. Next, the MCT oil adhering to the obtained capsules was removed, dried, and washed with ethanol to produce spherical seamless soft capsules having a frosted, almost colorless capsule coating on the surface. The coating rate of the seamless soft capsules was 12%, the coating thickness was 112 μm, and the size was 7.1 mm.

[0074] <Manufacturing Example 2> Except for changing the formulation of the capsule coating solution used in Manufacturing Example 1 to one that does not use erythritol, spherical seamless soft capsules with a glossy, nearly colorless, transparent capsule coating were manufactured using the same method as in Manufacturing Example 1. The coating rate of the seamless soft capsules was 12%, the coating thickness was 123 μm, and the size was 7.0 mm.

[0075] <Manufacturing Example 3> A spherical, seamless soft capsule with a glossy, nearly colorless, transparent capsule coating was manufactured using the same method as in Manufacturing Example 2, except that the ratio of the capsule coating solution to the capsule contents was changed. The seamless soft capsule had a coating density of 8%, a coating thickness of 100 μm, and a size of 6.7 mm. <Manufacturing Example 4> Spherical seamless soft capsules with a glossy, brown, transparent capsule coating were manufactured using the same method as in Manufacturing Example 2, except that caramel coloring (0.5 kg) was added to the capsule coating solution in Manufacturing Example 2. The coating rate of the seamless soft capsules was 12%, the coating thickness was 120 μm, and the size was 7.0 mm.

[0076] <Stability Test> The stability of seamless soft capsules manufactured in Manufacturing Examples 1-4 was evaluated. The capsule contents (without capsule coating) from Manufacturing Example 1 were used as a comparative example. As shown in Table 1 below, the residual CDB (Cellular Dioxide) content was measured by liquid chromatography when stored under specified conditions in each storage container.

[0077] The following equipment was used in this test. Fluorescent lamp: FL20SS-EX-D / 18M (manufactured by Panasonic Corporation) Digital illuminance meter: LX-1000 (manufactured by Custom Co., Ltd.) Data logger / temperature / humidity meter: SK-L200TH IIα (manufactured by Sato Keiryoki Seisakusho Co., Ltd.)

[0078] The conditions for liquid chromatography are as follows: Detector: Photodiode array (Measurement wavelength: 220nm) Column: Chemco pak CHEMCOSORB 5-ODS-H Column temperature: 30℃ Sample cooler temperature: 5℃ Injection volume: 10μL Flow rate: 1.0mL / min Mobile phase A: Water / acetic acid (1000 / 1) Mobile phase B: Acetonitrile / acetic acid (1000 / 1) (From 0 to 20 minutes after injection, the mixing ratio of mobile phases A and B is changed, such as mobile phase A from 50 to 30 vol% and mobile phase B from 50 to 70 vol%.)

[0079] The results of the stability test are shown in Table 1. [Table 1]

[0080] In photostability tests for drug approval applications, stability when exposed to a total illuminance of 1.2 million lux·hr is required. Here, a total illuminance of 1.2 million lux·hr corresponds to 25 days of exposure at 2000 lux in Table 1. As shown in Table 1, in the comparative example without a capsule coating, the remaining CBD rate decreased significantly as the storage period under light irradiation lengthened, whereas in the seamless soft capsule formulations of Manufacturing Examples 1-4, no significant decrease in the remaining CBD rate was observed, confirming superior stability.

Claims

1. Capsule coating and The contents enclosed in the aforementioned capsule membrane, Includes, The contents include cannabidiol, The thickness of the capsule coating is 10 to 200 μm. Seamless soft capsules for sublingual or oral administration.

2. A seamless soft capsule according to claim 1, which is rapidly dissolving in the oral cavity.

3. A seamless soft capsule according to claim 1, which is easily ruptured in the oral cavity.

4. The seamless soft capsule according to any one of claims 1 to 3, wherein the coating rate of the seamless soft capsule is 3 to 50%.

5. The seamless soft capsule according to any one of claims 1 to 4, wherein the diameter of the seamless soft capsule is 1 to 20 mm.

6. A seamless soft capsule according to any one of claims 1 to 5, wherein the contents consist solely of cannabidiol as the cannabinoid.

7. Container and A seamless soft capsule according to any one of claims 1 to 6, placed in the container, Includes, A product in which only cannabidiol is listed as a cannabinoid among the ingredients of the aforementioned seamless soft capsules.

Images