Composition and capsule formulation

Abstract

To provide a composition that contains ubiquinone powder having a melting point of 50°C or lower and has satisfactory flowability even if the composition does not contain a large amount of magnesium stearate and silicon dioxide, a capsule formulation into which the composition is filled, and a method for producing the formulation.SOLUTION: A composition according to the present invention contains ubiquinone powder having a melting point of 50°C or lower, and cellulose powder having an average particle diameter D50 of 80 μm or more. In the composition, it is preferable that a content of the cellulose powder with respect to the total amount of the composition be twice or more the content of the ubiquinone powder with respect to the total amount of the composition. it is preferable that the composition do not contain magnesium stearate and silicon dioxide. In a method for producing a capsule formulation according to the present invention, the composition is filled into a capsule.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for health food or pharmaceutical use containing an active ingredient with a low melting point, and a capsule preparation filled with said composition. [Background technology]

[0002] Capsule formulations are formulations in which a composition containing an active ingredient is filled inside a capsule. There are two types of capsule formulations: hard capsules, in which a powder or granular composition is filled into a cylindrical body and cap, and soft capsules, in which a liquid or paste-like composition is encapsulated with a film-like coating. In particular, hard capsule formulations are suitable for formulations of active ingredients with low thermal stability because they can be prepared by simply filling the capsule body with the composition and fitting the cap, and do not require heat treatment. For example, lipid-soluble active ingredients are not suitable for tableting because the active ingredient melts under tableting pressure, causing oil stains, and therefore capsule formulations are preferably selected.

[0003] As with other formulations, it is important for capsule formulations to minimize variations in the active ingredient content among individual formulations. To improve the uniformity of the active ingredient content, the fluidity of the active ingredient is important. Capsule formulations are manufactured by supplying a powdered or granular composition containing the active ingredient through a supply port, filling the capsule body, and then fitting a cap. If the raw material composition has good fluidity, it can be smoothly supplied through the supply port, easily filled into the capsule, and weight variations among capsules are unlikely to occur. However, active ingredients that have a low melting point and are easily melted by heat generated by friction, etc., can have problems such as poor fluidity due to adhesion to the inner wall of the capsule filling machine or other raw material powders, resulting in large variations in the active ingredient content.

[0004] Attempts have been made to improve the thermal stability and formulation operability of low-melting fat-soluble compounds, which are problems in formulation. For example, Patent Document 1 discloses a method of mixing a low-melting fat-soluble compound in a molten state with a porous substance, and using the composition retained in the porous substance as a raw material to formulate the compound. By retaining the compound in a porous substance, the thermal stability of the fat-soluble compound is improved and melting during the manufacturing process is suppressed, resulting in improved flowability. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2005-104934 Summary of the Invention [Problem to be solved by the invention]

[0006] In recent years, consumer demand for clean label formulations has led to a demand for formulations that do not contain artificial-sounding or misleading ingredients. For example, formulations that do not contain chemically synthesized substances such as silicon dioxide or magnesium stearate are preferred as clean label formulations. However, silicon dioxide and magnesium stearate are commonly used additives to improve flowability. In particular, formulations containing low-melting, fat-soluble compounds as active ingredients cannot be formulated without these additives, resulting in significantly reduced flowability and greater variability in drug content.

[0007] The present invention has been made in consideration of the above circumstances, and provides a composition containing ubiquinone powder having a melting point of 50°C or less, which has good fluidity even though it does not contain large amounts of magnesium stearate and silicon dioxide, a capsule formulation filled with the composition, and a method for producing the same. [Means for solving the problem]

[0008] That is, the present invention includes the following aspects. [1] Ubiquinone powder with a melting point of 50°C or less and an average particle size D50 and a cellulose powder having a particle size of 80 μm or more. [2] The composition of [1], wherein the content of magnesium stearate relative to the total amount of the composition is 0.0% by mass or more and 0.1% by mass or less, and the content of silicon dioxide relative to the total amount of the composition is 0.0% by mass or more and 0.1% by mass or less. [3] The composition according to [1] or [2] above, wherein the content of the cellulose powder relative to the total amount of the composition is 1.5 times or more the content of the ubiquinone powder relative to the total amount of the composition. [4] Ubiquinone powder with a melting point of 50°C or less and an average particle size D 50 and a cellulose powder having a particle size of 80 μm or more, A method for producing a composition, comprising producing a composition having a magnesium stearate content of 0.1 mass% or less relative to the total amount of the composition and a silicon dioxide content of 0.1 mass% or less relative to the total amount of the composition. [5] A method for producing a capsule formulation, comprising filling a capsule with any one of the compositions [1] to [3] above. [6] The method for producing a capsule formulation according to [5], wherein the composition is filled into capsules in an environment of 40°C or less. [7] A capsule formulation filled with any one of the compositions [1] to [3] above. [Effects of the Invention]

[0009] According to the above embodiment, it is possible to provide a composition containing ubiquinone powder having a melting point of 50°C or less, which has good fluidity even though it does not contain large amounts of magnesium stearate and silicon dioxide, and a capsule formulation filled with the composition. DETAILED DESCRIPTION OF THE INVENTION

[0010] Hereinafter, a mode for carrying out the present invention (hereinafter simply referred to as "the present embodiment") will be described in detail. The following present embodiment is an example for explaining the present invention, and is not intended to limit the present invention to the following content. The present invention can be carried out by appropriately modifying it within the scope of its gist.

[0011] In the present invention and the present specification, the average particle size of powders such as cellulose is the average particle size D measured with a laser diffraction / scattering particle size distribution analyzer (LA-950 V2 (trade name), manufactured by Horiba, Ltd.). 50 is.

[0012] In the present invention and the present specification, the angle of repose (°) of powders such as cellulose and compositions is a value measured using a Sugihara-type angle of repose measuring device.

[0013] <Composition> The composition of the present embodiment comprises ubiquinone powder having a melting point of 50° C. or less and an average particle diameter D 50 The composition of this embodiment contains cellulose powder having an average particle diameter D of 80 μm or more. Ubiquinone powder with a melting point of 50° C. or less is easily melted on the production line, and conventionally, sufficient amounts of magnesium stearate and silicon dioxide are blended to improve flowability. The composition of this embodiment has an average particle diameter D 50 By blending cellulose powder having a particle size of 80 μm or more, the composition has excellent fluidity even if it does not contain large amounts of magnesium stearate and silicon dioxide.

[0014] [Ubiquinone powder] The ubiquinone contained in the composition of this embodiment is a benzoquinone derivative, an electron carrier involved in oxidation-reduction reactions in the body, and is also known as coenzyme Q. Examples of ubiquinone include coenzyme Q6, coenzyme Q7, coenzyme Q8, coenzyme Q9, coenzyme Q10, coenzyme Q11, and coenzyme Q12. Also included are their reduced forms (also known as ubiquinol). The ubiquinone contained in the composition of this embodiment is not particularly limited, as long as it is a powder of these ubiquinones with a melting point of 50°C or lower. Furthermore, the ubiquinone contained in the composition of this embodiment may be one type or two or more types.

[0015] The ubiquinone powder contained in the composition of the present embodiment may be a purified product synthesized by a microorganism or the like, or may be a chemically synthesized product. Alternatively, commercially available ubiquinone powder may be contained in the composition of the present embodiment.

[0016] The ubiquinone powder contained in the composition of this embodiment has an average particle diameter D 50 is preferably 1 μm or more and 200 μm or less, and more preferably 1 μm or more and 100 μm or less.

[0017] The content of ubiquinone powder in the composition of this embodiment is typically 1% by mass or more and 50% by mass or less, preferably 5% by mass or more and 50% by mass or less, more preferably 5% by mass or more and 45% by mass or less, even more preferably 5% by mass or more and 40% by mass or less, even more preferably 10% by mass or more and 40% by mass or less, and particularly preferably 15% by mass or more and 35% by mass or less, relative to the total amount of the composition (total mass of the composition).

[0018] [Cellulose powder] Cellulose is a naturally occurring, water-insoluble fibrous material that contains cellulose. The cellulose used as the raw material for the cellulose powder contained in the composition of this embodiment can be cellulose obtained by hydrolysis or other treatment of cellulose raw materials such as wood pulp, non-wood pulp, wheat straw, rice straw, cotton, cotton linter, hemp, ramie, bagasse, kenaf, beet, sea squirt, and bacterial cellulose. The cellulose raw material is preferably wood pulp or non-wood pulp, more preferably bleached wood pulp (BP), wood-dissolving pulp (DP), or cotton linter pulp, and even more preferably bleached wood kraft pulp (BKP) or wood-dissolving kraft pulp (DKP). One of these may be used as the cellulose raw material, or a mixture of two or more may also be used.

[0019] The cellulose powder contained in the composition of the present embodiment has an average particle diameter D 50The particle size is not particularly limited as long as it is 80 μm or more. Generally, "cellulose powder" is referred to as crystalline cellulose, powdered cellulose, etc., and is suitable for use as a pharmaceutical additive or food additive. It may also be a cellulose powder processed with cellulose and a component other than cellulose, such as silicic acid-treated crystalline cellulose (SMCC) described in the Pharmaceutical Additives Standards 2018.

[0020] Among these, crystalline cellulose is preferred as the cellulose powder to be contained in the composition of this embodiment. As the crystalline cellulose, at least one that conforms to the identification test for microcrystalline cellulose described in the 9th edition of the Official Specification of Food Additives, and more preferably one that conforms to the identification test for crystalline cellulose described in the Japanese Pharmacopoeia (18th edition), may also be used. Alternatively, crystalline cellulose described in the United States Pharmacopoeia, the European Pharmacopoeia, etc. may also be used.

[0021] The average particle diameter D of the cellulose powder contained in the composition of this embodiment 50 The average particle diameter D of the cellulose powder contained in the composition of the present embodiment is 80 μm or more, preferably 85 μm or more, and more preferably 90 μm or more. 50 The upper limit is not particularly limited, but is preferably 200 μm or less, more preferably 150 μm or less, even more preferably 120 μm or less, and even more preferably 100 μm or less.

[0022] The content of cellulose powder contained in the composition of this embodiment is preferably 1% by mass or more and 80% by mass or less, more preferably 10% by mass or more and 70% by mass or less, and even more preferably 20% by mass or more and 70% by mass or less, based on the total amount of the composition. When the content of cellulose powder is equal to or more than the above-mentioned lower limit, the fluidity of the composition is more excellent. On the other hand, when the content of cellulose powder is equal to or less than the above-mentioned upper limit, sufficient amounts of other components such as ubiquinone can be contained.

[0023] The angle of repose of the cellulose powder contained in the composition of this embodiment is not particularly limited, but is preferably 55° or less, more preferably 52° or less, and even more preferably 50° or less. Furthermore, the angle of repose of the cellulose powder contained in the composition of this embodiment is preferably 25° or more, more preferably 28° or more, even more preferably 30° or more, and even more preferably 33° or more. By ensuring that the angle of repose of the cellulose powder is equal to or less than the above upper limit, the fluidity of the pharmaceutical composition can be further improved.

[0024] [Ratio of cellulose powder content to ubiquinone powder content] The content of the cellulose powder relative to the total amount of the composition in the present embodiment is preferably 1.5 times or more the content of the ubiquinone powder relative to the total amount of the composition. 50 If the ratio of [content (mass) of cellulose powder having a particle size of 80 μm or more] / [content (mass) of ubiquinone powder relative to the total amount of the composition]) is 1.5 or more, the average particle size D 50 The cellulose powder having a particle size of 80 μm or more fully exhibits the effect of improving the flowability of the ubiquinone powder. The content ratio of the cellulose powder to the ubiquinone powder in the composition of this embodiment is preferably 2.0 or more, and more preferably 2.5 or more. In order to allow a sufficient amount of ubiquinone powder to be contained, the content ratio of the cellulose powder to the ubiquinone powder in the composition of this embodiment is preferably 8.0 or less, more preferably 6.0 or less, and even more preferably 4.0 or less.

[0025] [Magnesium stearate and silicon dioxide] In the composition of this embodiment, the content of magnesium stearate relative to the total amount of the composition is preferably 0.0% by mass or more and 0.1% by mass or less, and the content of silicon dioxide relative to the total amount of the composition is preferably 0.0% by mass or more and 0.1% by mass or less. In other words, it is more preferable that the composition of this embodiment does not contain magnesium stearate or silicon dioxide in an amount sufficient to improve the flowability of the composition. The composition of this embodiment has an average particle diameter D 50A composition that does not contain magnesium stearate and silicon dioxide is more preferred because the flowability improving effect of the cellulose powder having a particle size of 80 μm or more is more effectively exhibited.

[0026] The composition of this embodiment preferably contains a low content of commonly used fluidizing agents other than silicon dioxide, for example, silicon compounds such as light anhydrous silicic acid, which are classified as fluidizing agents in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), and more preferably does not contain these fluidizing agents.

[0027] The composition of this embodiment preferably contains a low content of commonly used lubricants other than magnesium stearate, such as calcium stearate, stearic acid, sucrose fatty acid esters, talc, sodium stearyl fumarate, and other lubricants classified as lubricants in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), and more preferably does not contain these lubricants.

[0028] [Other ingredients] In addition to the ubiquinone powder and the cellulose powder, the composition of this embodiment may further contain one or more additives commonly used in pharmaceuticals, particularly capsule formulations. These additives are preferably in the form of powder. The other additives may include, for example, excipients (excluding the cellulose powder), binders, disintegrants, and colorants.

[0029] Examples of excipients other than cellulose powder include starch acrylate, L-aspartic acid, aminoethylsulfonic acid, aminoacetic acid, candy (powder), gum arabic, powdered gum arabic, alginic acid, sodium alginate, pregelatinized starch, pumice granules, inositol, ethyl cellulose, ethylene vinyl acetate copolymer, sodium chloride, olive oil, kaolin, cacao butter, casein, fructose, pumice granules, carmellose, carmellose sodium, hydrated silicon dioxide, dry yeast, dried aluminum hydroxide gel, dried sodium sulfate, dried magnesium sulfate, and Ingredients: agar, agar powder, citric acid, sodium citrate, disodium citrate, glycerin, calcium glycerophosphate, sodium gluconate, L-glutamine, clay, clay 3, clay granules, croscarmellose sodium, crospovidone, magnesium aluminosilicate, calcium silicate, magnesium silicate, light anhydrous silicic acid, light liquid paraffin, cinnamon powder, Genmai Koji, synthetic aluminum silicate, synthetic hydrotalcite, sesame oil, wheat flour, wheat germ flour, rice flour, rice starch, potassium acetate, calcium acetate, cellulose acetate phthalate, Safflower oil, white beeswax, zinc oxide, titanium dioxide, magnesium oxide, β-cyclodextrin, dihydroxyaluminum aminoacetate, 2,6-di-butyl-4-methylphenol, dimethylpolysiloxane, tartaric acid, potassium hydrogen tartrate, calcined gypsum, sucrose fatty acid ester, magnesium alumina hydroxide, aluminum hydroxide gel, aluminum hydroxide-sodium bicarbonate coprecipitate, magnesium hydroxide, squalane, stearyl alcohol, stearic acid, calcium stearate, polyoxyethylene stearate, magnesium stearate Sodium, hardened soybean oil, refined gelatin, refined shellac, refined white sugar, refined white sugar spherical granules, cetostearyl alcohol, polyethylene glycol 1000 monocetyl ether, gelatin, sorbitan fatty acid ester, tricalcium phosphate, soybean oil, soybean unsaponifiables, soybean lecithin, skim milk powder, talc, ammonium carbonate, calcium carbonate, magnesium carbonate, neutral anhydrous sodium sulfate, low-substituted hydroxypropyl cellulose, dextran, dextrin, natural aluminum silicate, tragacanth powder, silicon dioxide, calcium lactate, Perfiller 101,White shellac, white petrolatum, hakudo, white sugar, white sugar and starch spherical granules, naked barley leaf extract powder, naked malt leaf green juice dried powder, honey, paraffin, potato starch, semi-digested starch, human serum albumin, hydroxypropyl starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate, hydroxypropyl methylcellulose phthalate, phytic acid, glucose, glucose hydrate, partially pregelatinized starch, pullulan, propylene glycol, powdered reduced maltose syrup, pectin, bentonite, sodium polyacrylate, polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene (105) polyoxypropylene (5) glycol, polyoxyethylene (160) polyoxypropylene (30) glycol, sodium polystyrene sulfonate, polyiso Examples of excipients include those classified as excipients in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as sorbate 80, polyvinyl acetal diethylaminoacetate, polyvinylpyrrolidone, polyethylene glycol, maltose, starch syrup, isopropyl myristate, anhydrous lactose, anhydrous calcium hydrogen phosphate, anhydrous calcium phosphate granules, magnesium aluminometasilicate, methylcellulose, cottonseed flour, cottonseed oil, Japan wax, aluminum monostearate, glycerin monostearate, sorbitan monostearate, medicinal charcoal, peanut oil, aluminum sulfate, calcium sulfate, granular cornstarch starch, liquid paraffin, dl-malic acid, calcium hydrogen phosphate, calcium hydrogen phosphate, calcium hydrogen phosphate granules, sodium hydrogen phosphate, potassium dihydrogen phosphate, calcium dihydrogen phosphate, and sodium dihydrogen phosphate. These may be used alone or in combination of two or more.

[0030] Examples of binders include sugars such as sucrose, fructose, lactose or lactose hydrate, fructooligosaccharides, glucose, palatinose, maltose, reduced maltose, powdered sugar, powdered candy, isomerized lactose, and honey sugar; sugar alcohols such as mannitol, xylitol, maltitol, erythritol, sorbitol, and lactitol; and water-soluble polysaccharides such as gelatin, pullulan, carrageenan, locust bean gum, agar, glucomannan, xanthan gum, tamarind gum, pectin, sodium alginate, and gum arabic. Examples of binders include those classified as binders in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha), such as celluloses such as hydroxypropyl cellulose and methyl cellulose, starches such as corn starch, potato starch, rice starch, pregelatinized starch, and starch paste, synthetic polymers such as polyvinylpyrrolidone, carboxyvinyl polymer, and polyvinyl alcohol, and inorganic compounds such as calcium hydrogen phosphate, calcium carbonate, synthetic hydrotalcite, and magnesium aluminosilicate. These binders may be used alone or in combination of two or more.

[0031] Examples of disintegrants include those classified as disintegrants in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha Co., Ltd.), such as celluloses such as croscarmellose sodium, carmellose, carmellose calcium, carmellose sodium, and low-substituted hydroxypropyl cellulose; starches such as carboxymethyl starch sodium, hydroxypropyl starch, rice starch, wheat starch, potato starch, pregelatinized starch, and partially pregelatinized starch; and synthetic polymers such as crospovidone and crospovidone copolymer. One type selected from these disintegrants may be used, or two or more types may be used in combination.

[0032] <Method of producing the composition> The composition of the present embodiment is a raw material ubiquinone powder and an average particle diameter D 50 The cellulose powder can be produced by dry mixing cellulose powder having a particle size of 80 μm or more with other raw material powders as required.

[0033] There is no particular limitation on the order in which the raw material powders are added, and there is also no particular limitation on the method of addition as long as it is a commonly used method. For example, the raw material powders may be added continuously using a small suction transport device, a pneumatic transport device, a bucket conveyor, a pressure-feed transport device, a vacuum conveyor, a vibrating metering feeder, a spray, a funnel, or the like, or may be added all at once.

[0034] The mixing method is not particularly limited as long as it is a commonly used method, and for example, a container rotation type mixer such as a V-type, W-type, double cone type, or container type mixer, or a stirring type mixer such as a high-speed stirring type, universal stirring type, ribbon type, Pug type, or Nauta type mixer may be used. A container shaking type mixer such as a shaker may also be used.

[0035] <Capsule formulation>

[0036] The capsule formulation of this embodiment is a capsule formulation filled with the composition of this embodiment. Because the composition of this embodiment has improved fluidity, the capsule formulation of this embodiment filled with this composition has excellent content uniformity of ubiquinone, which is an active ingredient.

[0037] <Capsule formulation manufacturing method> The method for producing a capsule formulation of this embodiment is a production method in which the composition of this embodiment is filled into capsules. As the capsules to be filled with the composition of this embodiment, hard capsules commonly used in the production of pharmaceuticals can be used as appropriate. Furthermore, filling of the composition of this embodiment into capsules can be carried out by a conventional method using a commonly used capsule manufacturing machine.

[0038] The temperature environment in which the composition of this embodiment is filled into capsules is preferably an environment of 40° C. or less, more preferably 35° C. or less, and even more preferably 30° C. or less. By filling into capsules at a temperature significantly lower than the melting point of ubiquinone, melting of ubiquinone due to frictional heat and the like generated in the production process can be further suppressed, and content uniformity can be further improved.

[0039] The resulting capsule formulation may be further coated. Examples of coating agents that can be used in this case include those listed in the "Dictionary of Pharmaceutical Additives" (published by Yakuji Nipposha). These coating agents may be used alone or in combination of two or more. [Example]

[0040] The present embodiment will be described in detail below with reference to examples and comparative examples, but the present embodiment is not limited thereto. The methods for measuring physical properties and evaluating tablets in the examples and comparative examples are as follows.

[0041] <Methods for measuring physical properties> The physical properties of the cellulose powder and the powder composition containing the same were measured using the methods described below.

[0042] [Physical Properties 1] (Angle of repose) Using a Sugihara-type angle of repose measuring device (slit size: depth 10 x width 50 x height 140 mm, protractor installed at the 50 mm width position), the powder composition to be measured was dropped into the slit using a quantitative feeder at a rate of 3 g / min, and the dynamic free flow properties were measured. The angle between the bottom of the device and the layer of the powder composition was taken as the angle of repose (°) of the powder composition.

[0043] [Physical Properties 2] (The average particle size of the cellulose powder D 50 ) The particle size of the granules was measured using a laser diffraction particle size distribution analyzer (LA-950 V2 (trade name), manufactured by Horiba, Ltd.) in dry measurement mode at a compressed air pressure of 0.10 MPa, a feeder speed of 160, a feeder initial velocity coefficient of 1.2, and a refractive index of 1.51. The particles at 50% cumulative volume obtained by the measurement were used as the average particle size D of the granules. 50 (μm).

[0044] [Examples 1 to 2, Comparative Examples 1 to 10] Powder compositions containing ubiquinone (CoQ10) (Examples 1 and 2, Comparative Examples 1 to 10) were prepared by manually mixing the ingredients according to the formulation shown in Table 1 in a plastic bag for 1 minute. The cellulose powders used were crystalline cellulose (MCC) powder A (Asahi Kasei Corporation, Ceolus PH-101), crystalline cellulose powder B (Asahi Kasei Corporation, Ceolus PH-102), crystalline cellulose powder C (Asahi Kasei Corporation, Ceolus UF-702), crystalline cellulose powder D (Asahi Kasei Corporation, Ceolus UF-702), crystalline cellulose powder E (Asahi Kasei Corporation, Ceolus UF-711), crystalline cellulose powder F (Asahi Kasei Corporation, Ceolus KG-802), crystalline cellulose powder G (Asahi Kasei Corporation, Ceolus KG-1000), and crystalline cellulose powder H (Asahi Kasei Corporation, Ceolus OD-20P). In the table, "mg-St" represents magnesium stearate, and "SiO" represents silicon dioxide.

[0045] [Table 1]

[0046] The angle of repose was determined for each powder composition obtained. The angle of repose was measured three times for each sample, and the average value was calculated. The measurement results of the angle of repose were used as the average particle diameter D of the crystalline cellulose powder used. 50 The values ​​are shown in Table 2 together with the particle size (μm).

[0047] [Table 2]

[0048] As shown in Table 2, when the results of the angles of repose of the powder compositions of Comparative Examples 1 to 6 and Examples 1 and 2 are compared, the average particle diameter D 50 The powder compositions of Examples 1 and 2, each having an average particle diameter D 50The angles of repose were clearly smaller and more fluid than those of the powder compositions of Comparative Examples 1 to 6, which used crystalline cellulose powder with a particle size of 20 μm or 50 μm. The angles of repose of the powder compositions of Examples 1 and 2 were also smaller than those of the powder compositions of Reference Examples 2 and 3, which used magnesium stearate and silicon dioxide. These results indicate that the powder compositions containing ubiquinone powder have a mean particle size D 50 It was found that by using crystalline cellulose powder with a particle size of 90 μm or more, the angle of repose becomes smaller and fluidity can be improved compared to when magnesium stearate and silicon dioxide are used. [Industrial Applicability]

[0049] Although the composition of this embodiment does not contain sufficient amounts of magnesium stearate and silicon dioxide, it is a ubiquinone-containing powder composition with good flowability and excellent uniformity of drug content by particle size. Therefore, by using this composition as a raw material, it is possible to provide a capsule formulation that does not contain magnesium stearate and silicon dioxide but has good uniformity of ubiquinone content.

Claims

1. Ubiquinone powder having a melting point of 50°C or less and an average particle diameter D ５０ and a cellulose powder having a particle size of 80 μm or more.

2. 2. The composition according to claim 1, wherein the content of magnesium stearate relative to the total amount of the composition is 0.0% by mass or more and 0.1% by mass or less, and the content of silicon dioxide relative to the total amount of the composition is 0.0% by mass or more and 0.1% by mass or less.

3. 2. The composition according to claim 1, wherein the content of said cellulose powder relative to the total amount of the composition is 1.5 times or more the content of said ubiquinone powder relative to the total amount of the composition.

4. Ubiquinone powder having a melting point of 50°C or less and an average particle diameter D ５０ and a cellulose powder having a particle size of 80 μm or more, A method for producing a composition, comprising producing a composition having a magnesium stearate content of 0.1 mass% or less relative to the total amount of the composition and a silicon dioxide content of 0.1 mass% or less relative to the total amount of the composition.

5. A method for producing a capsule formulation, comprising filling the composition according to any one of claims 1 to 3 into a capsule.

6. The method for producing a capsule formulation according to claim 5, wherein the composition is filled into capsules in an environment of 40°C or less.

7. A capsule formulation filled with the composition according to any one of claims 1 to 3.

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