Vitamin C-containing granules, tablets containing vitamin C-containing granules, method for manufacturing vitamin C-containing granules

Abstract

To provide granules containing a high concentration of vitamin C that can improve the moldability and disintegration property in tableting, because, when vitamin C is added at a high concentration, not only the moldability in the tableting but also the disintegration property of the formulations is lowered, in vitamin C-containing granules.SOLUTION: In order to solve the above problems, a vitamin C-containing granule characterized by containing vitamin Cs, catechins, and celluloses is provided. Thereby, it is possible to provide granules containing a high concentration of vitamin C, which contributes to the improvement of the moldability and disintegration property of the formulation in tableting.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to vitamin C-containing granules, a tablet containing vitamin C-containing granules, and a method for producing vitamin C-containing granules. More specifically, the present invention relates to vitamin C-containing granules for use in the fields of pharmaceuticals, health foods and the like, a tablet containing vitamin C-containing granules, and a method for producing vitamin C-containing granules. [Background Art]

[0002] Vitamin C is a type of water-soluble vitamin called ascorbic acid (L-ascorbic acid), VC, etc., and is a substance that cannot be synthesized in the human body. Vitamin C has many physiological functions: not only the effect of suppressing reactive oxygen species as an antioxidant, but also an immunostimulatory effect in the infection defense mechanism, a histamine-suppressing effect in allergic reactions, an effect as a coenzyme in collagen synthesis, an effect of suppressing the production of melanin pigment, a chelating effect on metals, an improving effect on bleeding tendency, a protective effect against stress responses, and an anti-aging effect.

[0003] Since water-soluble vitamin C has a shorter retention time in vivo compared to fat-soluble vitamins, humans are prone to vitamin C deficiency. Therefore, in the fields of pharmaceuticals, foods, cosmetics, etc., products formulated with vitamin C are provided. However, vitamin C has a strong sour taste, making it difficult to ingest a large amount of preparation at one time. Accordingly, oral preparations that contain vitamin C at a high concentration and achieve a sufficient intake with a limited number of doses have been studied. As an oral preparation containing a high concentration of vitamin C, for example, Patent Document 1 discloses hard granules containing 80 to 90 mass% of vitamin C, which are produced by granulating a granulation mixture containing vitamin C, a sweetener, and a paste while dropping a mixture of ethanol and water, and then evaporating ethanol and water in the granules. [Prior Art Literature] [Patent Literature]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 4-295425 [Overview of the project] [Problems that the invention aims to solve]

[0005] The vitamin C-containing granules described in Patent Document 1 contain 80-90% by mass of vitamin C, but granules containing even higher concentrations of vitamin C are desired. However, incorporating high concentrations of vitamin C not only reduces the moldability during formulation, but also reduces the disintegration properties of the formulation due to the decrease in the proportion of additives. Therefore, granules containing high concentrations of vitamin C that contribute to improving both the moldability during formulation and the disintegration properties of the formulation are desired. The object of the present invention is to provide granules containing a high concentration of vitamin C that can improve moldability and disintegration properties of formulations during formulation. [Means for solving the problem]

[0006] As a result of diligent research into the above-mentioned problems, the inventors of the present invention have found that by incorporating catechins and celluloses into granules containing vitamin C, the moldability and disintegration properties of the formulation can be improved, and have completed the present invention.

[0007] In other words, the present invention provides the following [1] to [8]. [1] Vitamin C-containing granules characterized by containing vitamin C derivatives, catechins, and cellulose derivatives. This vitamin C-containing granule allows for the creation of granules with improved moldability during formulation due to the action of cellulose compounds, and improved disintegration properties due to the action of catechin compounds. [2] The vitamin C-containing granules according to [1], characterized in that the ratio of the content of cellulose to the content of catechins is 2.5 to 20.0. This characteristic allows for further improvement in moldability and disintegration properties of the formulation by controlling the ratio of catechins and cellulose contained in the granules. [3] The vitamin C-containing granules according to [1] or [2], characterized in that the vitamin C content is 90 to 97% by mass. This characteristic makes it possible to provide granules containing a high concentration of vitamin C. [4] The vitamin C-containing granules according to [1] to [3], characterized in that the vitamin C derivative is at least one selected from the group consisting of sodium ascorbate, calcium ascorbate, and ascorbyl palmitate. Based on these characteristics, by using sodium ascorbate, calcium ascorbate, and ascorbyl palmitate as vitamin C derivatives, the physiological effects of vitamin C can be further enhanced. [5] The vitamin C-containing granules according to [1] to [4], characterized in that the catechins are at least one selected from the group consisting of catechin gallate, epigallocatechin gallate, gallocatechin gallate, and epicatechin gallate. Based on these characteristics, the disintegration properties of the formulation can be further improved by using catechin gallate, epigallocatechin gallate, gallocatechin gallate, and epicatechin gallate as catechin compounds. [6] The vitamin C-containing granules according to [1] to [5], characterized in that the cellulose is at least one selected from the group consisting of hydroxypropylcellulose and hydroxypropylmethylcellulose. According to these characteristics, by using hydroxypropyl cellulose and hydroxypropyl methylcellulose as cellulose compounds, the moldability in formulation can be further improved. A tablet characterized by containing vitamin C-containing granules as described in any of [7][1] to [6]. According to this tablet, by using the vitamin C-containing granules described in [1] to [6], a tablet with excellent moldability and disintegration properties can be produced. [8] A method for producing vitamin C-containing granules, comprising the steps of: mixing vitamin C derivatives and catechin derivatives; and granulating the mixture of vitamin C derivatives and catechin derivatives while spraying cellulose derivatives onto it. According to this method for producing vitamin C-containing granules, by adding cellulose to a mixture of vitamin C and catechins, the moldability and disintegration properties of the formulation can be improved. [Effects of the Invention]

[0008] According to the present invention, it is possible to provide granules containing a high concentration of vitamin C that contribute to improving moldability and disintegration properties of formulations. [Modes for carrying out the invention]

[0009] The following describes in detail embodiments of the vitamin C-containing granules, a method for producing the vitamin C-containing granules, and tablets containing the vitamin C-containing granules according to the present invention. The vitamin C-containing granules, methods for producing vitamin C-containing granules, and tablets containing vitamin C-containing granules described in the embodiments are merely illustrative examples for the purpose of explaining the present invention and are not limiting.

[0010] [Vitamin C-containing granules] The vitamin C-containing granules of the present invention contain catechins and celluloses. The celluloses contained in the vitamin C-containing granules improve the moldability of the granule components due to their high binding strength. On the other hand, celluloses develop viscosity when they come into contact with water, such as when taken orally, reducing the disintegration properties of the formulation. Catechins suppress the viscosity development of celluloses induced by moisture, thereby improving the reduced disintegration properties of the formulation. As a result, the vitamin C-containing granules of the present invention can exhibit the effect of improved moldability and disintegration properties in formulation.

[0011] The particle size of vitamin C-containing granules is not particularly limited as long as they have the form of granules. For example, the particle size of vitamin C-containing granules is between 100 μm and 1500 μm. The upper limit is more preferably 1000 μm or less, even more preferably 700 μm or less, and particularly preferably 600 μm or less. The lower limit is more preferably 200 μm or more, even more preferably 300 μm or more, and particularly preferably 400 μm or more. The particle size of vitamin C-containing granules can be measured by the particle size test method described in the 17th edition of the Japanese Pharmacopoeia. By setting the particle size of the vitamin C-containing granules within the above range, the optimal form for granules can be achieved.

[0012] First, we will explain in detail each component that makes up the vitamin C-containing granules. Unless otherwise specified, the content of each component refers to the content in the vitamin C-containing granules.

[0013] (Vitamin C) Vitamin C derivatives are those that possess an ascorbic acid skeleton and exhibit similar physiological activity to vitamin C, and are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and animal feed. Examples of vitamin C derivatives include vitamin C, vitamin C derivatives, and their salts. Specific examples of vitamin C include ascorbic acid, ascorbic acid metal salts such as sodium ascorbate, potassium ascorbate, and calcium ascorbate, and ascorbyl palmitate. Specific examples of vitamin C derivatives include, for example, phosphorylated ascorbic acid; metal salts of phosphorylated ascorbic acid such as sodium phosphorylated ascorbate, potassium phosphorylated ascorbate, and calcium phosphorylated ascorbate; ascorbic acid bound to fatty acids such as ascorbyl palmitate, ascorbyl laurate, ascorbyl myristate, ascorbyl stearate, and ascorbyl tetrahexyldecanoate; and ascorbic acid bound to monosaccharides such as glycosylated ascorbic acid, mannosylated ascorbic acid, fructosylated ascorbic acid, fucosylated ascorbic acid, galactosylated ascorbic acid, N-acetylglucosaminated ascorbic acid, and N-acetylmuramylated ascorbic acid. Preferable vitamin C derivatives are sodium ascorbate, calcium ascorbate, and ascorbyl palmitate from the viewpoint of physiological action. Furthermore, these vitamin C derivatives may be incorporated alone, or may be incorporated in a combination of two or more types.

[0014] The content of vitamin C derivatives is not particularly limited. The content of vitamin C derivatives is preferably 90% by mass or more and 97% by mass or less. By setting the content of vitamin C derivatives within the above range, granules containing a high concentration of vitamin C can be obtained.

[0015] (Catechins) Catechins are flavonoid compounds having a flavan-3-ol skeleton, and are not particularly limited as long as they are acceptable for uses such as pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and feeds. Examples of catechins include free catechins, gallate-type catechins, and salts thereof. Furthermore, catechins may be purified products, or may be green tea extract which is a crudely purified product extracted from leaves of Camellia sinensis and the like. Specific examples of free catechins include catechin, epigallocatechin, gallocatechin, and epicatechin, for example. Specific examples of gallate-type catechins include catechin gallate, epigallocatechin gallate, gallocatechin gallate, and epicatechin gallate. These catechins may be blended singly or in a combination of two or more kinds.

[0016] The content of the catechins is not particularly limited. For example, the content of the catechins is 0.01% by mass or more and 4.0% by mass or less. The lower limit is more preferably 0.05% by mass or more, still more preferably 0.1% by mass or more, and particularly preferably 0.12% by mass or more. On the other hand, the upper limit is more preferably 3.0% by mass or less, still more preferably 2.5% by mass or less, and particularly preferably 2.0% by mass or less. By setting the content of the catechins within the above range, the disintegratability of the preparation can be further improved.

[0017] (Celluloses) Celluloses are polymer compounds having a structure in which a large number of β-glucose molecules are linearly polymerized via glycosidic bonds, and are not particularly limited as long as they are acceptable for uses such as pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and feeds. Examples of the celluloses include cellulose derivatives and salts thereof. Specific examples of the cellulose derivatives include: hydroxyalkyl celluloses such as hydroxypropyl cellulose, hydroxyethyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose acetate succinate, and hydroxypropyl methyl cellulose phthalate; alkyl celluloses such as methyl cellulose and ethyl cellulose; and carboxyalkyl celluloses such as carboxymethyl cellulose, potassium carboxymethyl cellulose, calcium carboxymethyl cellulose, sodium carboxymethyl cellulose, carboxymethyl ethyl cellulose, croscarmellose sodium, and croscarmellose. Preferred celluloses, from the viewpoint of moldability in formulation, are hydroxypropyl cellulose and hydroxypropyl methylcellulose. These celluloses may be blended individually or in combination of two or more.

[0018] The cellulose content is not particularly limited. For example, the cellulose content is 0.1% by mass or more and 10.0% by mass or less. The lower limit is more preferably 0.3% by mass or more, and even more preferably 0.4% by mass or more. On the other hand, the upper limit is more preferably 9.0% by mass or less, and even more preferably 8.0% by mass or less. By setting the cellulose content within the above range, the moldability of the formulation can be further improved.

[0019] The ratio of cellulose content to catechin content is, for example, 2.5 to 20.0. The lower limit is more preferably 2.8 or higher, and even more preferably 3.0 or higher. On the other hand, the upper limit is more preferably 15.0 or lower, and even more preferably 13.0 or lower. By setting the ratio of cellulose content to catechin content within the above range, the moldability and disintegration properties of the formulation can be further improved.

[0020] (Other ingredients) The vitamin C-containing granules of the present invention may contain additives in addition to vitamin C derivatives, catechins, and cellulose derivatives, as needed. Specific examples of additives include, for example, excipients, sweeteners, acidulants, flavorings, and coloring agents.

[0021] Excipients adjust the volume of the granular composition and are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and animal feed. Examples of excipients include dextrin, starch, sugars, sugar alcohols, cellulose, and microcrystalline cellulose. These excipients may be blended individually or in combination of two or more. The size of the granules can be adjusted by adding excipients.

[0022] Sweeteners are substances that impart sweetness to granules, and are not particularly restricted as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, animal drugs, and animal feed. Examples of sweeteners include natural sweeteners and artificial sweeteners. Specific examples of sweeteners include erythritol, sorbitol, aspartame, acesulfame potassium, stevia, sucralose, glycyrrhizic acid, thaumatin, saccharin, and sodium saccharin. These sweeteners may be used individually or in combination of two or more. By adding a sweetener, the granules can be made sweeter and easier to take.

[0023] Acidulants are substances that impart a sour taste to granules, and are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and animal feed. Examples of acidulants include organic acids such as citric acid, malic acid, and succinic acid, and inorganic acids such as phosphoric acid. These acidulants may be used individually or in combination of two or more. By adding an acidulant, the granules can be given a sour taste, making them easier to take.

[0024] The fragrance is intended to enhance the oral sensory perception of the granules and is not particularly limited as long as it is acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary medicines, and animal feed. The fragrance may be in either liquid or powder form. Specific examples of fragrances include spearmint oil, peppermint oil, cinnamon oil, and fruit essences. These fragrances may be blended individually or in combination of two or more. Adding flavorings can make the granules easier to take.

[0025] Colorants are used to improve the palatability and distinguishability of granules, and are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and animal feed. Examples of colorants include natural pigments and synthetic pigments. Specific examples of colorants include, for example, cochineal, carmine, curcumin, riboflavin, annat, titanium dioxide, yellow ferric oxide, ferric oxide, talc, calcined silica, magnesium carbonate, and synthetic food colorants such as Food Blue No. 1, Food Blue No. 2, Food Yellow No. 4, Food Yellow No. 5, Food Green No. 3, Food Red No. 2, Food Red No. 3, Food Red No. 102, Food Red No. 104, Food Red No. 105, and Food Red No. 106. These colorants may be blended individually or in combination of two or more. By adding coloring agents, the granules can be colored, thereby improving their palatability and distinguishability.

[0026] Due to the above characteristics, the vitamin C-containing granules of the present invention can exhibit the effect of improving moldability and disintegration properties of formulations through the action of catechins and celluloses.

[0027] [Method for manufacturing vitamin C-containing granules] The method for producing the vitamin C-containing granules of the present invention can utilize conventional methods used in the technical fields of pharmaceuticals, quasi-drugs, cosmetics, food, and animal feed. Specific methods for manufacturing vitamin C-containing granules include, for example, a step of mixing vitamin C compounds and catechin compounds, and a step of granulating the mixture of vitamin C compounds and catechin compounds while spraying cellulose compounds onto it.

[0028] The method for mixing the granular components is not particularly limited, as long as it is a common method used in the art. Examples of mixers used in these mixing methods include tumbler mixers, V-type mixers, double-cone mixers, agitator mixers, high-speed fluidized mixers, drum mixers, fluidized bed mixers, and infinite mixers.

[0029] The granulation method for granular components is not particularly limited, as long as it is a common method used in the art. Examples of granulation methods include wet granulation, dry granulation, heat granulation, and spray granulation. From the viewpoint of versatility, wet granulation is the preferred granulation method. Specific examples of wet granulation methods include fluidized bed granulation, agitation granulation, extrusion granulation, crushing granulation, and rolling granulation. Examples of granulators used in these granulation methods include fluidized bed granulators, rolling fluidized bed granulators, Worster-type granulators, rolling-type granulators, agitation granulators, heat granulators, and spray granulators.

[0030] The drying method for granules is not particularly limited, as long as it is a common method used in this art. Examples of drying methods include spray drying, fluidized bed drying, shelf drying, vacuum drying, vibration drying, microwave drying, and freeze drying. Examples of drying equipment used in these methods include spray dryers, fluidized bed dryers, heated / vacuum dryers, and freeze dryers.

[0031] Based on the above characteristics, the method for producing vitamin C-containing granules of the present invention can provide vitamin C-containing granules that contribute to improving moldability and disintegration properties of formulations.

[0032] [Uses of Vitamin C-containing granules] The uses of the vitamin C-containing granules of the present invention are not particularly limited. For example, the vitamin C-containing granules can be used in pharmaceuticals, quasi-drugs, cosmetics, foods, animal drugs, animal feed, etc. Furthermore, pharmaceuticals, quasi-drugs, cosmetics, foods, and animal feeds containing vitamin C granules are used for human or non-human animals. Non-human animals are not particularly limited, but examples include mammals, birds, reptiles, amphibians, and fish, and preferably include chickens, cattle, pigs, dogs, and cats.

[0033] There are no particular restrictions on the form of pharmaceuticals, quasi-drugs, cosmetics, foods, and animal feeds that contain vitamin C-containing granules. Examples of forms of products containing vitamin C-containing granules for oral administration include tablets such as sugar-coated tablets, buccal tablets, film-coated tablets, and chewable tablets, as well as granules, capsules, lozenges, and pills. In the food sector, products utilizing vitamin C-containing granules include health foods (nutritional supplements, functional foods, foods for the sick, foods for specified health uses, foods with functional claims, etc.), supplements, foods for the sick (hospital meals, sick person meals, nursing care meals, etc.), and health supplements. From the standpoint of versatility and convenience, preferred forms are tablets, granules, and capsules.

[0034] (tablet) The tablets are not particularly limited as long as they contain vitamin C-containing granules. For example, the tablets may contain only vitamin C-containing granules as the active ingredient, or they may contain other active ingredients, additives, etc. The amount of vitamin C-containing granules contained in the tablets is preferably 70% to 90% by mass. The amount of vitamin C derivatives contained in the tablets is preferably 60% to 90% by mass.

[0035] The moldability of the vitamin C-containing granules of the present invention in tablet formation is not particularly limited, as long as it does not affect the disintegration properties of the desired tablet and productivity can be maintained. Examples of moldability in tablet formation include the relationship between tableting pressure and tablet hardness. A desirable indicator of moldability is, for example, a tablet pressure of 1000 kgf or less when producing a tablet with a hardness of 10 kgf, a diameter of 8 mm, and a weight of 300 mg.

[0036] The shape of the tablet is not particularly limited, as long as it is used in the technological fields of pharmaceuticals, quasi-drugs, cosmetics, food, and animal feed. Examples of tablet shapes include round tablets, oval tablets, and flower-shaped tablets. Furthermore, the molded body may be provided with one or two score lines for dividing into two or four parts as needed. The size of the tablets is not particularly limited. For example, the diameter of the tablets is 3 mm or more and 50 mm or less. The lower limit is more preferably 4 mm or more, even more preferably 5 mm or more, and particularly preferably 6 mm or more. On the other hand, the upper limit is more preferably 40 mm or less, even more preferably 30 mm or less, and particularly preferably 20 mm or less. The thickness of the tablet is not particularly limited. For example, the tablet thickness is between 1.0 mm and 20.0 mm. The lower limit is more preferably 2.0 mm or more, even more preferably 2.5 mm or more, and particularly preferably 3.0 mm or more. On the other hand, the upper limit is more preferably 15.0 mm or less, even more preferably 12.0 mm or less, and particularly preferably 10.0 mm or less. By setting the size and thickness of the tablets within the above range, it is possible to create tablets that are easy to swallow.

[0037] Tablets are not particularly limited as long as they contain vitamin C-containing granules. In addition to vitamin C-containing granules, tablets may contain other active ingredients, additives, etc., as needed. Examples of additives include excipients, binders, disintegrants, thickeners, plasticizers, stabilizers, preservatives, sugars, film coating agents, sweeteners, acidulants, colorants, lubricants, photoprotectants, and flavorings. The explanations of excipients, sweeteners, acidulants, flavorings, and colorants overlap with the explanations in the (Other Ingredients) section above, so they are omitted here.

[0038] Other specific examples of active ingredients include, for example, vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, folic acid, biotin, niacin, pantothenic acid, iron, copper, zinc, manganese, selenium, chromium, molybdenum, polyglutamic acid, vine tea polyphenols, lipid regulators, antidiabetic agents, appetite suppressants, antihypertensive agents, vasodilators, β-adrenergic receptor blockers, cardiac ion channel agents, antiarrhythmic agents, anticoagulants, central nervous system function improvers, sympathetic nerve stimulants, parasympathetic nerve stimulants, antimuscarinic agonists, dopamine agonists, tranquilizers, antidepressants, antiepileptic agents, and anxiolytics. Examples of active ingredients include hypnotics, stimulants, animal-derived substances, plant-derived substances, rapidine, nobiletin, sulforaphane, ampelopsin, curcumins, resveratrols, geraniol, osadin, isoliquitigenin, hydroxytyrosol, 25-hydroxycholecalciferol, S-adenosylmethionine, anthocyanins, ascorbic acid 2-glucoside, proteoglycans, N-acetylglucosamine, collagen, bilberry extract, carrot powder, goji rhizome, licorice, peony, cinnamon, fennel, cardamom, bifidobacteria, lactic acid bacteria, yeast, and dietary fiber such as polydextrose. These active ingredients may be combined individually or in combination of two or more.

[0039] The binder enhances the binding strength of the granular component composition and is not particularly limited as long as it is acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and animal feed. Examples of binders include synthetic resins, sugars, polyethers, and waxes. Specific examples of binders include, for example, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, glucose, sucrose, lactose, maltose, dextrin, sorbitol, mannitol, polyethylene glycol, paraffin, gum arabic, gelatin, agar, starch, and pullulan. These binders may be formulated individually or in combination of two or more. By adding a binder, the granular component composition is given binding strength, making it possible to produce stable granules.

[0040] Disintegrants enhance the disintegration properties of formulations by increasing their water absorption, and are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and animal feed. Examples of disintegrants include sugars, synthetic resins, and alginates. Specific examples of disintegrants include corn starch, sodium carboxymethyl starch, polyvinylpyrrolidone, sodium alginate, and sodium starch glycolate. These disintegrants may be used individually or in combination of two or more. By adding a disintegrant, the disintegration of granules can be accelerated, improving absorption.

[0041] Thickening agents impart viscosity to the component composition of granules and are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and animal feed. Examples of thickening agents include polysaccharides and water-soluble acrylic acid polymers. Specific examples of thickening agents include sodium alginate, xanthan gum, guar gum, carboxyvinyl polymer, carrageenan, gellan gum, pectin, gum arabic, and roasted bean gum. These thickening agents may be used individually or in combination of two or more. The size of the granules can be adjusted by adding a thickening agent.

[0042] Plasticizers impart flexibility and elasticity to the granular component composition and are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, food products, animal drugs, and animal feed. Examples of plasticizers include polyethers, polyhydric alcohols, esters, organic acids, and vegetable oils. Specific examples of plasticizers include polyethylene glycol, polypropylene glycol, glycerin, glycerol, polyol, triethyl citrate, acetyl monoglyceride, butylphthalylbutyl glycolate, dibutyl tartrate, propylene glycol, glycerol monostearate, tripioin, diacetin, citric acid, medium-chain fatty acid oil, and rapeseed oil. The molecular weight of polyethylene glycol is, for example, between 4,000 and 20,000. Specific examples of polyethylene glycol include PEG6000 and PEG8000. These plasticizers may be blended individually or in combination of two or more. By adding plasticizers, the flexibility and elasticity of the granular component composition can be adjusted, thereby improving moldability.

[0043] Stabilizers inhibit the chemical and physical decomposition of granular components and are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and animal feed. Examples of stabilizers include inorganic compounds, organic acids, organic acid salts, and vitamins. Specific examples of stabilizers include sodium bisulfite, sodium edetate, and tocopherol. These stabilizers may be used individually or in combination of two or more. By adding a stabilizer, the deactivation of granular components can be suppressed.

[0044] Preservatives inhibit the growth of microorganisms and are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and animal feed. Examples of preservatives include benzoates and para-hydroxybenzoic acid esters. Specific examples of preservatives include sodium benzoate, propyl parahydroxybenzoate, methylparaben, and propylparaben. These preservatives may be used individually or in combination of two or more. Adding preservatives can prevent microbial contamination of the granules.

[0045] Sugars are the main components of sugar coatings and are not particularly restricted as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and animal feed. Examples of sugars include monosaccharides, disaccharides, and sugar alcohols. Specific examples of sugars include glucose, sucrose, lactose, sorbitol, mannitol, xylitol, erythritol, and maltitol. These sugars may be blended individually or in combination of two or more types. Adding sugars can improve the palatability of the granules.

[0046] Film coating agents are base materials used in compositions for film coating granules, and are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, food products, animal drugs, and animal feed. Examples of film coating agents include synthetic resins and polysaccharides. Specific examples of film coating agents include polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, pullulan, zein, shellac, and yeast. These film coating agents may be formulated individually or in combination of two or more. By adding a film coating agent, the efficiency and performance of the film coating can be improved.

[0047] Lubricants reduce the adhesion of powder components and improve fluidity, and are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, food products, animal drugs, and animal feed. Examples of lubricants include phyllosilicate mineral powders, silicon oxides, saturated fatty acids, esters, waxes, hydrogenated vegetable oils, fats, and polyethers. Specific examples of lubricants include, for example, fine silicon dioxide, light anhydrous silicic acid, calcium stearate, magnesium stearate, sodium stearyl fumarate, talc, magnesium carbonate, sodium benzoate, palmitic acid, beeswax, hydrogenated soybean oil, cocoa butter, and polyethylene glycol. These lubricants may be blended individually or in combination of two or more. By adding a lubricant, the occurrence of tableting defects such as sticking during tablet manufacturing can be suppressed.

[0048] Photoprotective agents impart light-shielding properties to granules and are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, food products, veterinary drugs, and animal feed. Examples of photoprotective agents include oxides and tar-based dyes. Specific examples of photoprotective agents include titanium dioxide, yellow iron(III) oxide, iron(III) oxide, food yellow No. 5, and food yellow No. 4. These photoprotective agents may be used individually or in combination of two or more. By adding a photoprotective agent, the components contained in the granules can be protected from light.

[0049] Other additives include solubilizers, surfactants, emulsifiers, antioxidants, glazing agents, foaming agents, moisture-proofing agents, preservatives, fluidizing agents, flavoring agents, cooling agents, flavoring agents, fragrances, and disintegration aids. These additives may be blended individually or in combination of two or more.

[0050] The method for manufacturing tablets containing vitamin C-containing granules can be the conventional methods used in the fields of pharmaceuticals, quasi-drugs, cosmetics, food, and animal feed. The mixing method, granulation method, and drying method of the granules in the tablet manufacturing method overlap with the explanation in the above section [Method for Manufacturing Vitamin C-Containing Granules], so the explanation is omitted here.

[0051] The method of tableting the tablet components is not particularly limited, as long as it is a common method used in the art. Examples of tableting methods include direct compression and granular compression. Examples of tablet presses used in these methods include single-shot presses, continuous presses, rotary presses, and multi-stage presses.

[0052] The method for film coating tablets is not particularly limited, as long as it is a common method used in the art. Examples of film coating methods include pan coating, fluid coating, and rolling coating. Examples of film coating apparatus used in these methods include pan coating apparatus and drum-type coating apparatus, and the spraying apparatus attached to the film coating apparatus may be an air spray type or an airless spray type.

[0053] The amount of film coating on the tablets is not particularly limited. For example, the amount of film coating is 0.1% by mass or more and 20.0% by mass or less per 100% by mass of the tablet. The lower limit is more preferably 0.5% by mass or more, even more preferably 1.0% by mass or more, and particularly preferably 2.0% by mass or more. On the other hand, the upper limit is more preferably 15.0% by mass or less, even more preferably 12.5% ​​by mass or less, and particularly preferably 10.0% by mass or less. By setting the amount of film coating on the tablets within the above range, the efficiency and effectiveness of the film coating can be fully realized.

[0054] (Granules) The granular preparation is not particularly limited as long as it contains vitamin C-containing granules. For example, the granular preparation may consist solely of vitamin C-containing granules, or it may be a mixture of granules containing other active ingredients, additives, etc. In addition to vitamin C-containing granules, the granular preparation may contain other active ingredients, additives, etc., as needed. Specific examples of other active ingredients and additives include, for example, active ingredients, excipients, binders, disintegrants, thickeners, plasticizers, stabilizers, preservatives, sugars, film coating agents, sweeteners, acidulants, colorants, photoprotective agents, solubilizers, surfactants, emulsifiers, antioxidants, glazing agents, foaming agents, moisture-proofing agents, preservatives, fluidizing agents, flavoring agents, cooling agents, flavoring agents, fragrances, aromatherapy agents, and disintegration aids. Since the explanation of additives and active ingredients overlaps with the explanations in the sections on (Other Ingredients) and (Tablets) above, the explanation is omitted here.

[0055] The method for producing granular preparations containing vitamin C granules can be the conventional methods used in the fields of pharmaceuticals, quasi-drugs, cosmetics, food, and animal feed. The mixing method, granulation method, and drying method of the granules in the production method of the granular preparation will be omitted here as they overlap with the explanation in the section on [Production Method of Vitamin C Granules].

[0056] (Capsule) Capsules are not particularly limited as long as they contain vitamin C-containing granules. For example, a capsule may contain only vitamin C-containing granules as the active ingredient, or it may contain other active ingredients, additives, etc. Capsules may contain other active ingredients, additives, etc., as needed, in addition to vitamin C-containing granules. Specific examples of active ingredients and additives include, for example, active ingredients, excipients, binders, disintegrants, thickeners, plasticizers, stabilizers, preservatives, sugars, film coating agents, sweeteners, acidulants, colorants, photoprotective agents, solubilizers, surfactants, emulsifiers, antioxidants, glossing agents, foaming agents, moisture-proofing agents, preservatives, fluidizing agents, flavoring agents, cooling agents, flavoring agents, fragrances, aromatherapy agents, and disintegration aids. Since the explanations of additives and active ingredients overlap with those in the sections on (other ingredients) and (tablets) above, they are omitted here.

[0057] Capsules are not particularly limited as long as they are acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary drugs, and animal feed. Examples of capsules include soft capsules made from agar, gelatin, gellan gum, etc., hard capsules made from gelatin, cellulose derivatives, pullulan, etc., and seamless capsules made from agar, gelatin, acrylic, urethane, etc. Specific examples of gelatin used as a base material for capsules include, for example, gelatin, acidic gelatin, alkaline gelatin, peptide gelatin, low molecular weight gelatin, and gelatin derivatives. Specific examples of cellulose derivatives used as a base material for capsules include alkylcellulose such as methylcellulose; hydroxyalkylcellulose such as hydroxymethylcellulose, hydroxyethylcellulose, and hydroxypropylcellulose; and hydroxyalkylalkylcellulose such as hydroxypropylmethylcellulose, hydroxyethylmethylcellulose, and hydroxyethylethylcellulose.

[0058] The method for producing capsules containing vitamin C granules can be the conventional methods used in the fields of pharmaceuticals, quasi-drugs, cosmetics, food, and animal feed. The mixing method, granulation method, drying method of the granules, and film coating method in the capsule production method overlap with the explanation in the above section [Production Method for Vitamin C Granules], (Tablets), and therefore the explanation is omitted here.

[0059] The method for filling capsule components into capsules is not particularly limited, as long as it is a common method used in the art. Examples of filling methods include hard encapsulation, rotary die encapsulation, and seamless encapsulation. Examples of filling machines used in these filling methods include hard capsule filling machines, fully automatic capsule filling machines, capsule filling and sealing machines, rotary die filling machines, and seamless capsule filling machines.

[0060] Due to the above characteristics, the vitamin C-containing granules of the present invention can be used in the manufacture of tablets, granules, capsules, and the like. [Examples]

[0061] The following describes embodiments of the present invention, but the present invention is not limited to these embodiments, and various modifications are possible within the technical concept of the present invention.

[0062] (Preparation of test samples) Granules containing the components shown in Tables 1 and 3, and tablets containing the components shown in Tables 2 and 4 were prepared. The numerical values ​​in the columns for each component in each table indicate the content of that component, and the unit is mass percent. Vitamin C used was 100 mesh ascorbic acid (BASF Japan Ltd.).

[0063] (Evaluation of tablet moldability) Tablets were formed using a tablet press (N-30E single-shot tablet press, Okada Seikou Co., Ltd.), yielding tablets with a diameter of 8 mm and a weight of 300 mg. To evaluate the moldability of the tablets, the compression pressure was measured when producing tablets with a hardness of 10 kgf, as confirmed by a hardness tester (New Speed ​​Checker TS-75N, Okada Seikou Co., Ltd.), using the tablet press (N-30E single-shot tablet press, Okada Seikou Co., Ltd.). When the compression pressure required to obtain a tablet with a hardness of 10 kgf is 1000 kgf or less, this is considered desirable moldability because it allows for improved productivity without reducing the disintegrability of the tablet.

[0064] (Evaluation of tablet disintegration properties) The disintegration properties of the tablets were evaluated by measuring the disintegration time when the tablets were placed in 900g of water at 38°C. If the disintegration time of a tablet is 10 minutes or less, it is evaluated as a tablet with the desired disintegration properties.

[0065] [Table 1]

[0066] [Table 2]

[0067] The moldability and disintegration properties of tablets prepared using the vitamin C-containing granules listed in Table 1, with the component composition listed in Table 2, were evaluated. As shown in Table 2, comparing Test Examples 1-8, in Test Examples 3-5, where the ratio of hydroxypropylcellulose to catechin in the vitamin C granules contained in the tablets was in the range of 3.3-12.8, the tablet compression pressure was 900 kgf or less and the disintegration time was 5 minutes or less. On the other hand, in Test Examples 1, 2, and 6, where the ratio of hydroxypropylcellulose to catechin in the vitamin C granules contained in the tablets was outside the range of 3.3-12.8, the tablet compression pressure was 1100 kgf or more and the disintegration time was 18 minutes or more. Furthermore, in Test Examples 7 and 8, tablet detachment (capping) occurred. Therefore, it was shown that the moldability and disintegration properties of tablets improved when the ratio of hydroxypropyl cellulose to catechin in vitamin C-containing granules was in the range of 3.3 to 12.8.

[0068] [Table 3]

[0069] [Table 4]

[0070] The moldability and disintegration properties of tablets prepared using the vitamin C-containing granules listed in Table 3, with the component composition listed in Table 4, were evaluated. As shown in Table 4, when comparing Comparative Examples 1 and 2, which contain the same amount of vitamin C as Example 1, a tablet made using granules containing 90% vitamin C, Example 1, in which catechin and hydroxypropyl cellulose were added during granulation, showed good moldability and disintegration, whereas Comparative Example 1, which did not contain catechin and hydroxypropyl cellulose, and Comparative Example 2, in which catechin and hydroxypropyl cellulose were added during tableting, showed reduced moldability and disintegration. Similar results were obtained in Comparative Examples 3 and 4, which contained the same amount of vitamin C as in Example 2, which was a tablet using granules containing 97% vitamin C. Furthermore, when comparing Reference Example 1 with Comparative Examples 1-4, when the amount of vitamin C contained in the tablets was low, desirable moldability and disintegration properties were observed regardless of the presence or absence of catechin and hydroxypropylcellulose. Therefore, it has been shown that when producing tablets containing a high concentration of vitamin C, incorporating catechin and hydroxypropyl cellulose at the time of granulation of the vitamin C-containing granules improves the moldability and disintegration properties of the tablets.

[0071] From these results, it was found that by incorporating hydroxypropylcellulose to catechin in a ratio of 3.3 to 12.8 during the granulation of vitamin C-containing granules, the moldability and disintegration properties of the tablets were improved. [Industrial applicability]

[0072] The present invention provides granules containing a high concentration of vitamin C that can improve moldability and disintegration properties in formulation. This makes it possible to provide pharmaceuticals such as tablets, quasi-drugs, oral cosmetics, health foods (nutritional supplements, functional foods, foods for the sick, foods for specified health uses, foods with functional claims, etc.), supplements, and animal feed with excellent moldability and disintegration properties.

Claims

1. Vitamin C, which is at least one selected from the group consisting of ascorbic acid, sodium ascorbate, calcium ascorbate, and ascorbyl palmitate. Catechins, at least one selected from the group consisting of catechin gallate, epigallocatechin gallate, gallocatechin gallate, and epicatechin gallate, and It contains at least one hydroxyalkylcellulose selected from the group consisting of hydroxypropylcellulose, hydroxyethylcellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose acetate succinate, and hydroxypropylmethylcellulose phthalate. The ratio of the hydroxyalkylcellulose content to the catechin content is 3.0 to 13.

0. Vitamin C-containing granules characterized by having a vitamin C content of 90 to 97% by mass.

2. A tablet characterized by containing 70% by mass or more and 90% by mass or less of the vitamin C-containing granules described in claim 1 within the tablet.

3. A method for producing vitamin C-containing granules, Vitamin C, which is at least one selected from the group consisting of ascorbic acid, sodium ascorbate, calcium ascorbate, and ascorbyl palmitate, A step of mixing a catechin, which is at least one selected from the group consisting of catechin gallate, epigallocatechin gallate, gallocatechin gallate, and epicatechin gallate, The process involves granulating a mixture of vitamin C compounds and catechin compounds while spraying at least one hydroxyalkylcellulose selected from the group consisting of hydroxypropylcellulose, hydroxyethylcellulose, low-substituted hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose acetate succinate, and hydroxypropylmethylcellulose phthalate, A method for producing vitamin C-containing granules, characterized in that the vitamin C content is 90 to 97% by mass, and the ratio of the hydroxyalkylcellulose content to the catechin content is 3.0 to 13.0.

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