TW200812571A - Sugar-coated preparation and process for producing the same - Google Patents

Abstract

A technique for producing a sugar-coated preparation which has sufficient hardness and is excellent in low moisture absorption, a deodorizing property and disintegratability easily in a short time is provided. Specifically, a sugar-coating liquid which can be preferably used in the production of a sugar-coated preparation using a continuous coating method in which a step of spraying the sugar-coating liquid and a drying step are simultaneously conducted, a sugar-coated preparation with a sugar-coating layer formed with the sugar-coating liquid, and a process for producing the same are provided. The sugar-coated preparation is produced using the sugar-coating liquid containing an ethyl acrylate/methyl methacrylate copolymer and a solvent wherein the concentration of the ethyl acrylate/methyl methacrylate copolymer is 0.01 to 10% by weight based on the total solid component.

Description

200812571 IX. Description of the Invention [Technical Field of the Invention] The present invention relates to a sugar-coated preparation and a method of producing the same. [Prior Art] Since the sugar-coated layer has a function of preventing oxygen, water, and odor components from passing through, the sugar-coated layer is excellent in low oxygen permeability, low moisture absorption, and odor-reducing property, and is suitable for the formulation of the ingredients of the stable chemical ingot. . For example, the garlic processing system has the effects of eliminating fatigue or nourishing and strengthening, enhancing the gastric contraction force, promoting metabolism, promoting blood flow, and protecting the liver, and is widely used as a medicine, but because of heat or moisture. The odor is caused by the influence, so most of the sugar coatings have been formulated. In addition, Methylmethionine sulfonium chloride (hereinafter also referred to as "MMSC") has the symptoms of improving gastric ulcer, duodenal ulcer, gastritis, and the like, and improving liver function in chronic liver diseases. It is widely used as a pharmaceutical product to alleviate the effects of various symptoms and the like. However, since MMSC has a property of decomposing by absorbing moisture in the air, the preparation containing MMSC has a problem of deterioration in quality such as odor, discoloration, and reduction in the content of active ingredients. Therefore, most of the MMSC preparations have been sugar-coated for the purpose of preventing moisture absorption (Patent Documents 1 and 2). In addition, sodium valproate is widely used as a small seizure, partial seizure, psychomotor seizure, and mixed seizures, such as personality disorders (hypermune, irritability, etc.) and anxiety Symptoms and 躁-5- 200812571 The use of drugs for the treatment of anxiety in depression. However, sodium valproate has a hygroscopic property and deliquescent property, and it has been prepared for the purpose of preventing the quality of the product after opening. (Patent Documents 3 and 4). The sugar-coating preparation is generally produced by spraying [1] a sugar coating liquid, [2] cooking, and [3] drying several times (for example, Patent Document 5). Among them, [2] cooking is a step in which the side of the sugar-coated preparation is completely embedded, so that the sprayed coating liquid is uniformly spread on the ingot, and it is an indispensable step when a sugar liquid having a high viscosity is usually used. On the other hand, the manufacturing method of the sugar-coated preparation containing such a step is disadvantageous in that a large amount of the sugar-coating liquid or the like is required for the prime ingot when a very long work is required. As a manufacturing method for overcoming the above-mentioned disadvantageous surface, a method of forming a coating layer by a method of producing a coating layer by drying a spray coating liquid to form a coating layer by a method of forming a coating layer (hereinafter also referred to as a continuous coating method) is reviewed. In the continuous coating method, since the spray coating liquid must be rapidly and uniformly spread on the core material such as a tablet, it is required to dilute the sugar coating liquid to lower the viscosity. Therefore, for example, a technique of forming a thin layer of sugar-coated layer using a sugar-coating liquid of suspended sugar and talc is developed (Patent Document 6). However, such a thin layer of sugar-coated layer has a problem of poor strength compared to conventional ones. In addition, as a method of improving the strength of the thin layer of the sugar-coated layer, for example, a technique of providing an intermediate layer between the film-coated ingot and the sugar-coated layer has been developed (Patent Document 7). However, since such a method involves modulating and spraying a coating liquid having a composition different from that of the sugar coating layer, it is difficult to say that it is very simple. Further, in place of the gum arabic or gelatin which is usually used as a binder, hydroxypropylmethylcellulose or hydroxypropylcellulose is used, and the viscosity of the coating liquid is also lowered (Patent Document 8). However, -6-200812571 The sugar-coated layer obtained by this method has a problem that the density of the sugar-coated preparation is low in oxygen permeability, low in moisture absorption, and poor in odor resistance. As described above, the method for producing a sugar-coated preparation or the sugar-coating liquid has been subjected to various reviews in terms of improvement in workability and formulation characteristics, but no technology has been developed. Patent Document 1: Japanese Laid-Open Patent Publication No. 2003-95928, Patent Document 2: JP-A-2003-95928 Patent Document 3: JP-A-2006-25696 No. 1 Patent Publication No. 4: JP-A No. 04-23 No. Japanese Unexamined Patent Publication No. JP-A No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. SUMMARY OF THE INVENTION [Disclosure of the Invention] The present invention provides a sugar coating preparation which is capable of producing a sufficient hardness in a short period of time and which is excellent in low hygroscopicity, odor resistance, and collapse property. technology. Specifically, a sugar coating preparation suitable for use in a continuous coating method in which a sugar coating liquid is sprayed and a drying step is used to produce a sugar coating preparation, a sugar coating preparation having the sugar coating layer formed from the sugar coating liquid, and a method for producing the same are provided. Question. The inventors of the present invention conducted various reviews on the composition of the coating liquid suitable for the continuous coating method. Next, it was found that a sugar coating liquid of 200812571 ethyl acrylate/methyl methacrylate copolymer was blended in a sugar-containing solvent at a specific ratio, and the physical properties suitable for the continuous coating method were obtained by using the continuous coating method of the sugar coating liquid having such a composition. The sugar-coated preparation of the formed sugar-coated layer has low hygroscopicity, deodorant property, and good collapse property, and the present invention has been completed. That is, the present invention provides a sugar coating liquid containing an ethyl acrylate-methyl methacrylate copolymer and a solvent, and the concentration of the ethyl acrylate/methyl methacrylate copolymer is 0.01 to 10% by weight based on the total solid content. A sugar coating liquid, a method of producing a sugar coating preparation using the sugar coating liquid, and a sugar coating preparation obtained by the production method. [Best Mode for Carrying Out the Invention] The sugar coating liquid of the present invention is a sugar-containing, ethyl acrylate-methyl methacrylate copolymer, and a solvent. The sugar to be used in the present invention is not particularly limited as long as it is usually used to form a sugar-coated layer of a sugar-coated preparation, and examples thereof include white sugar, refined white sugar, white sugar, glucose, and trehalose. Among them, white sugar, fine white sugar and white sugar can be used. In the sugar coating liquid of the present invention, the amount of the sugar is not particularly limited, but is usually 10 to 85% by weight, preferably 10 to 70% by weight, particularly preferably 15 to 60% by weight. The ethyl acrylate/methyl methacrylate copolymer used in the present invention means a polymer obtained by copolymerizing ethyl acrylate and methyl methacrylate. The number average molecular weight of the copolymer may be within a range that imparts appropriate hardness and collapse to the sugar coating preparation, but is usually 10,000 to 1,500,000, preferably 400,000 200812571 to 1,200,000, and 500,000 to 151 Å. Yu Youjia. Further, the molar ratio of ethyl acrylate and methyl methacrylate constituting the copolymer is usually 10:1 to 1:10, preferably 4:1 to 1:4, and further, 3:1 to 1: 3 is especially good. Further, the glass transition temperature of the copolymer is usually in the range of _ 40 ° C to 30 ° C, preferably - 30 ° C to 20 ° C, preferably - 20 ° C to 10 ° C. The ethyl acrylate-methyl methacrylate copolymer can be obtained by copolymerizing ethyl acrylate and methyl methacrylate according to a usual method. Further, a commercially available product can also be used as the propylene φ acid ethyl ester/methyl methacrylate copolymer. As a commercially available product, for example, Eudragit NE30D (樋□ Chamber of Commerce), Colicoat EMM30D (BASF Japan), which disperses an ethyl acrylate/methyl methacrylate copolymer in water emulsion, can be used. In the sugar coating liquid of the present invention, the amount of the ethyl acrylate/methyl methacrylate copolymer is 0.01 to 1% by weight based on the total solid content contained in the sugar coating liquid. Among them, 〇·1 to 8 wt% is preferred. When the compounding amount exceeds 1% by weight, the solid matter suspended in the sugar coating liquid is agglomerated, which is not suitable. φ In the sugar coating liquid of the present invention, the mass ratio of ethyl acrylate·methyl methacrylate copolymer to sugar is usually 1: 1 to 1 : 1 0, 0 0 0 to 1: 3 to 1 : 1,000 It is advisable to take 1: 5~1: 5 00 especially good. The solvent of the sugar coating liquid of the present invention is not particularly limited as long as it is usually used as a sugar coating liquid. For example, a lower alcohol such as water, ethanol or isopropyl alcohol, acetone or a mixture of these may be mentioned. Of these solvents, usually purified water is suitable for use. The amount of the solvent in the sugar-coating liquid is not particularly limited, but is usually from 1 5 to 90% by weight, preferably from 1 5 to 85% by weight, particularly preferably from 20 to 80% by weight, particularly preferably from -9 to 200812571. When the amount of the solvent is more than 90% by weight, the working time for forming the sugar-coated layer becomes long, and it is difficult to form a dense sugar-coated layer, which affects the stability of the drug contained in the core material. In addition, when the amount is less than 15% by weight, the viscosity of the coating liquid becomes high, and the tablet adheres to the flatness of the tablet coating device, and the like, and when the sugar coating preparation is produced by the continuous coating method, the ingot cannot be used. The surface of the agent is evenly spread out of the sugar coating liquid, and a sugar coating layer of uniform thickness cannot be formed. In addition, the viscosity of the sugar-coating liquid may be as long as it can be sprayed by the device used for the manufacture of the sugar-coated preparation, and the amount of the solvent may be adjusted to be 3 to 1,000 cp, preferably 5 to 700 cp, and 10 to 400 cp. good. In addition to the above-mentioned respective components, the sugar-coating liquid of the present invention may be blended with any of various components which can be orally administered as the medical additive is allowed. As such an additive, for example, a coating agent, a coloring agent, a photo-forming agent, and the like can be given. As the coating agent, there are hydroxypropylcellulose, hydroxypropylmethylcellulose 2910, hydroxypropylmethylcellulose 2208, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, crystalline cellulose, gum arabic powder. , refined shellac, pululolan, precipitated calcium carbonate, talc, calcium hydrogen phosphate, light phthalic anhydride, aqueous cerium oxide, titanium oxide, sodium dihydrogen phosphate, hardened oil, glyceryl monostearate and mono-hard fat The acid polyethylene glycol ester or the like is preferably used in an amount of 〇80% by weight based on the sugar coating liquid. As the coloring agent, for example, various food coloring matters, tar coloring matter, and ferric oxide are used, and the compounding amount is preferably 〇·1% by weight or less based on the sugar coating preparation. The glossing agent is, for example, a palmetto or a bee sting, and the compounding amount is -10-200812571, preferably 3% by weight or less based on the sugar-coated preparation. The viscosity of the sugar coating liquid of the present invention is usually 3 to 1, 〇〇〇 cp, preferably 5 to 700 cp, and particularly preferably 10 to 400 cP. When a sugar coating liquid having such a viscosity range is used, when a sugar coating preparation is produced by a continuous coating method, a uniform sugar coating layer is easily formed. The sugar coating liquid of the present invention can be produced from a suspension sugar, an ethyl acrylate-methyl methacrylate copolymer, and any of the above-mentioned optional components in a solvent. In this case, it is preferred to sufficiently disperse the ethyl acrylate-methyl methacrylate copolymer in a solvent to add a surfactant. The sugar-coating preparation of the present invention is applied around a drug-containing core material and has at least one layer of a sugar coating layer formed using the sugar coating liquid of the present invention. The sugar-coated preparation of the present invention contains, as a core material containing a drug, a plain ingot or a core particle. That is, the sugar-coating preparation of the present invention may be in the form of, for example, a sugar-coated tablet or a sugar-coated granule. In the present invention, the drug to be safely administered by the oral administration is not particularly limited as long as it is suitable for the sugar-coated preparation, and may be, for example, a drug having an unpleasant odor. It is advisable to use drugs that are not stable in water, drugs that produce whiskers, and the like. Examples of the drug having an unpleasant odor include a crude drug (oxoquinone powder, hop, coix seed, medicine, mantis, scutellaria, fennel, clove, ginger, and medlar extract), and garlic processing. As a drug that is unstable to water, for example, vitamin A, vitamin B!, vitamin beta 2, vitamins, etc. B6, vitamin B12, vitamin C, vitamin 〇-11 - 200812571, vitamin E, biotin, calcium pantothenate, nicotinamide, vitamin P and its derivatives, etc.), methionine, Amino acids (aspartic acid and L-cysteine, etc.), adenosine triphosphate 2 sodium salt, enzymes (starch digestive enzymes, protein digestive enzymes, fat digestive enzymes and cellulose digestive enzymes, etc.), C Sodium valerate, Ibuprofen, Guaifenesin, and Scopolamine Butylbromide, etc., as a drug for generating whiskers, for example, Ibuprofen, anhydrous coffee Cause, B Aniline (Ethenzamide), propyphenazone (Isopropylantipyrine) L- menthol and the like. The compounding amount of these drugs may be appropriately adjusted depending on the use of the drug, but it is preferably 0.1 to 99% by weight, more preferably 1 to 85% by weight, based on the core material. In the present invention, as the drug contained in the core material, for example, the following drugs are preferable. [Garlic processed product] The garlic processed product is obtained by processing the bulb of Allium sativum 1. The method of processing is not particularly limited, and for example, the raw garlic is dried and powdered, and the raw garlic is extracted by steam distillation, oil, water, hot water or a water-soluble organic solvent, and the raw garlic is heated. Wait for the processor. Examples of the oil for extraction include edible vegetable oils such as rapeseed oil, olive oil, and soybean oil. Examples of the water-soluble organic solvent include lower alcohols such as ethanol and isopropyl alcohol; and glycols such as propylene glycol and diethylene glycol. Alcohol, etc. As a garlic processing system, after drying, powdering, by low -12-

200812571 alcohol extractor, heating processing processor is especially good. It can also be a commercial item. For example, processing garlic, garlic extract, and drying the big _ temple is suitable for processing Dahe Youjia. The garlic is heat-treated with a lower alcohol, and dried, for example, as commercially available from Oxoamidine (registered trademark) and Oxoredine (registered trademark) ( ). The garlic extract is, for example, a commercially available garlic industry (stock), and a garlic extract (Japanese, dried garlic, for example, commercially available garlic powder, manufactured by Yankee Chemical Industry Co., Ltd.). Such commercially available Oxoamidine (registered trademark) (Technology Oxoredine (registered trademark) (the skilled chemical worker wears the extract (A1 ps music industry (share)), > powder medicine (share)) Garlic processed material 5 is suitably adjusted for use, but it is preferably 5 to 15% by weight, preferably relative to %. [Methylthiomethic acid] methionine acid (MMSC) In addition, as a commercial product, for example, a commercially available Toshihide Pharmaceutical Co., Ltd., manufactured by Alps Pharmaceutical Co., Ltd., etc., it is preferably 1 to 80% by weight based on the core material, and further, MMSC is blended. In the core material, in addition, the garlic processed product: the liquid extract and the garlic extract are processed here, and the garlic system is processed. Garlic powder for extracts (Lily Chemical Industry (Liquor Chemicals (A1 ps music, 〖End drug (shares)) and other Qin garlic powder EX (Like garlic processed by Industrial Co., Ltd.) , industry (stock) system, large C garlic flow extract (sakamoto: the amount can be adjusted according to the sugar core material 2 ~ 30 weight according to the known manufacturing method of methyl thiomethic acid (M MMSC compounding amount Department 1 0~40% by weight, especially containing neutralizing gastric acid component-13-200812571 or inhibiting gastric acid secretion (acidic component), improving gastric function (stomach component), auxiliary digestion (digestive enzyme), repair The composition of the gastric mucosa (mucosal repair component) is particularly preferable. As the acid component, for example, synthetic Hydrotalcite, sodium hydrogencarbonate, magnesium niobate aluminate, aluminum hydroxide, sodium hydrogencarbonate coprecipitate, hydrazine extract, hydrogen Alumina, sodium bicarbonate, magnesium carbonate, precipitated calcium carbonate, precipitated magnesium carbonate, dihydroxy aluminum amine acetate, magnesium hydroxide, magnesium oxide, dried aluminum hydroxide gel, magnesium niobate aluminate, magnesium niobate , synthetic aluminum citrate, thunder hydrochloride Cimetidine (Ranitidine Hydrochloride), cimetidine (Cimetidine), Famotidine, Nizatidine (Nizatidine), Misaki pull nizatidine (Lafutidine), Omeprazole, Lansoprazole,

Pantoprazole, rabebeprazole sodium, Reminoprazole, Esomeprazole, Pirenzepine Hydrochloride, proglumide, and the like. As a healthy stomach ingredient, for example, Le powder, hop extract, gentian extract, fennel powder, ginger powder, clove powder, wild tung powder, brown catechu powder, turmeric powder, ebony powder, black glutinous powder , Astragalus powder, Cork powder, Huanglian powder, Zhizhu powder, Pueraria powder, licorice powder, glutinous powder, cinchona bark powder, Sophora flavescens powder, cinnamon powder, cassia seed powder, beef seedling powder, red ginseng powder, Magnolia Powder, Wujing powder, gallnut powder, African anti-root powder, dried tangerine powder, mountain sandalwood powder, pepper powder, Shannai powder, perilla powder, sand-reducing powder, small glutinous powder, green skin powder, sarcophagus root powder, atractylodes powder, Suye powder, rhubarb powder, bamboo ginseng powder, spruce powder, bitter tree powder, meat-14- 200812571 Dengqi powder, ginseng powder, diewood powder, glutinous powder, atractylodes powder, woody powder, puzzle powder , bayberry skin powder, peppermint oil, gentian (Gentiana triflora powder), ginger powder, fennel fruit, aloe vera, sleeping leaf, big fennel , Condurango, processed garlic, calamus root, hunter, horseback extract, dried yeast, Carnitine Hydrochloride, glutamic acid, Bethanechol chloride, trimebutine maleate Trimebutine Maleate) and so on.

Examples of the digestive enzyme include a compound enzyme (Biodiastase), a lipase, a ursodeoxycholic acid, a pepsin, a Diasmen, a cellulase, and a Cellulosin. Peak amylase (Taka — Diastase), bile powder, dehydrocholic acid, Newlase, Pancreatin, Biotamilase, Prozyme, Polypase, etc. As the mucosa repairing component, for example, sucralfate, Aldioxa, L-glutamine, Sofalcone, sodium copper chlorophyllin, potassium chlorophyllin, CeUaxate Hydrochloride , Gefarnate, Trimebutine Maleate, Sodium azulenesulfonate, and the like. [Sodium valproate] The sodium valproate system can be obtained according to a known production method (for example, Japanese Laid-Open Patent Publication No. SHO 60-165 663, JP-A-62-110604, JP-A-63- Japanese Patent Publication No. 122646 and Japanese Patent Laid-Open No. Hei 10-13019 No. 7). In addition, 15-200812571 is commercially available, for example, sodium valproate (manufactured by Nippon Synthetic Chemical Industry Co., Ltd., Alibaba). The amount of sodium valproate is preferably from 1 to 80% by weight, more preferably from 30 to 60% by weight, based on the core material. Further, in addition to the above-mentioned drugs, the core material may be blended with any of the various components which can be orally administered as needed. Examples of the various additives which can be administered orally, such as excipients, binders, disintegrators, and slip agents, may be used as excipients, and examples thereof include lactose, crystalline cellulose, sucrose, and mannose. Sugar alcohol, light phthalic anhydride, calcium hydrogen phosphate and corn starch. Examples of the binder include, for example, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, gelatin, polyvinylpyrrolidone, and sulphate, as a breaker, and for example, Carmellose calcium, Low substitutions include propylcellulose, Crospovidone, and Cross Carmellose Sodium. • The slip agent may, for example, be magnesium stearate, calcium stearate or talc. The core material used in the sugar coating preparation of the present invention can be produced by a usual method using a drug and other optional ingredients. For example, in the case of a plain ingot, the method of granulating the drug and any other additives, or the method of granulating the compounding drug and any other additives, and then granulating the powder into a powder by a granulator After the body is added, the powder of any other additives may be added or mixed in the powder, and the powder may be ingot or directly mixed with the drug and any other additives to granulate-16-200812571 , the method of ingoting by a tablet machine, and the like. Here, examples of the granulation include a dry granulation method and a wet granulation method, and the dry granulation method does not use a liquid such as water, ethanol, isopropyl alcohol or a mixed liquid thereof, and is granulated by dry granulation. A method in which a powder is compression-molded to produce a plate-like solid, which is then destroyed to produce a granular material. In addition, the wet granulation method refers to the use of a high-speed stirring granulator, a kneading granulator, a fluidized bed granulator, a rotary flow granulator, etc., and a binder is added to the powder to form particles, and then dried. The method, the type of the binding liquid is not particularly limited, but water, ethanol, isopropyl alcohol, and the like can be used. Next, in the case of the core particles, for example, a method of granulating a compounded drug and any other additives by a dry granulation method, a wet granulation method or a combined wet granulation method and extrusion granulation method, and granules are carried out. Method of chemistry, etc. The sugar-coated preparation of the present invention comprising at least one layer of the sugar-coated layer covering the core material is characterized by comprising 0.01 to 10% by weight of a sugar and an ethyl acrylate-methyl methacrylate copolymer. Further, the sugar-coating preparation of the present invention may have a coating layer of one layer or a plurality of layers formed of another coating liquid in addition to the sugar coating layer of one layer or a plurality of layers formed by the sugar coating liquid of the present invention. In the present specification, the layer formed of the sugar coating liquid of the present invention is referred to as a "sugar coating layer", and the layer formed of the coating layer other than the sugar coating layer of the present invention is described as a "coating layer". The coating layer can be classified into a plurality of layers such as a protective coating, a subcoating, a smoothing, a coloring -17·200812571 coloring, and a polishing layer according to the function. Wait. The ratio of the layers to the entire coating layer is usually 0 to 20% for the waterproof layer, 15 to 100% for the powder coating layer, 0 to 50% for the smooth layer, 〇~50% for the color coat layer and 0 for the polishing layer. ~1 0%. The waterproof layer is used in the sugar coating step to inhibit the movement of moisture to the core material. Further, the powder coating layer is used to trim the shape of the sugar-coated ingot, and the appearance and strength of the sugar-coated tablet are affected by the quality of the coating layer. Further, the smoothing layer is used to smooth the surface of the sugar-coated ingot, and the coloring layer is colored to enhance the visibility of the sugar-coated ingot or the commercial price, and the polishing layer is applied to impart gloss to the sugar-coated lozenge. The sugar-coated preparation of the present invention does not necessarily have all the coating layers having the above functions, but it is preferable to use a coating layer having a function of a coating layer, and the coating layer formed by using the coating liquid of the present invention can be suitably used as a coating layer function. The coating layer is suitable. Further, the sugar-coating preparation of the present invention may be coated with a release control layer different from the above-mentioned coating layer depending on the purpose. The release control layer may be one or more layers for performing functions for imparting dissolution of the drug contained in the control core material. The release control layer is directly coated on the core material, or may be applied between any of the above-mentioned waterproof layer, powder coating layer, smoothing layer, color coating layer and polishing layer, and is usually coated on the core material. When the control layer is released, it is preferably 1 to 1% by weight, more preferably 2 to 8% by weight, based on 1 part by weight of the sugar coating preparation. In addition, the method of using the release control layer or the component can be used, and the weight of the sugar coating layer formed by using the sugar coating liquid of the present invention in the sugar coating preparation of the present invention is 5 to 60% by weight based on the weight of the core material. It is preferable to use 1 〇 to 50% by weight. If the weight of the sugar-coated layer exceeds 60% by weight, since the coating step of 200812571 is long, the quality of the finished agent is increased with respect to the quality of the core material to be added, so that if another coating device is required, if it is less than 5% by weight In addition, since a sufficient coating layer is not obtained, since the coating layer is thin, there is a problem that contents such as environmental humidity or core particles cannot be obtained. The moisture absorption rate in the sugar coating preparation of the invention is 85% under the condition of temperature and humidity, and is preferably 1.0% or less under the condition of 24 hours, especially preferably B, and the temperature and humidity are 40 ° C -75%, 30 days later. The article is preferably 4.0% or less, and preferably 3.0% or less. Further, the degree of the damage can be appropriately adjusted in accordance with the purpose of use or the core material of the sugar-coated preparation of the present invention. When the core material of the sugar-coating preparation of the present invention contains a garlic processed product, the hardness of the agent is preferably 100 N or more, more preferably 110 N or more, and the degree of collapse is preferably within 25 minutes. When the core material of the sugar-coating preparation of the present invention contains MMSC, the hardness is preferably 65 N or more, and more preferably 70 N or more. The degree of badness is within 15 minutes. When the core material of the sugar-coating preparation of the present invention contains sodium valproate, the hardness is preferably 65 N or more, and more preferably 70 N or more. The sugar coating preparation of the present invention is obtained by simultaneously performing the sugar coating step of the present invention and the continuous coating method of the drying step to form a sugar coating layer, that is, by spraying the sugar coating liquid of the present invention under the drug-containing core material to coat the sugar coating of the core material. The solvent in the liquid scatters to form a sugar, and the core material (primary ingot or core particle) can be used to form a sugar coating problem. In addition, the hardness of the protective ingot is 25 ° C - 乂 0.5 %, and the hardness or the disintegration of the drug is good. In addition, the sugar-coated preparation is additionally produced by spraying a sugar-coated preparation liquid. The coat layer is also dried. Another sugar-coated tablets or -19- 200812571 sugar-coated granules. In the manufacture of a sugar ingot, a protective ingot containing a drug-containing ingot or a water-repellent layer is added to the continuous rotating coating device. For the spinning of the ingot or the protective ingot in the device, the spraying and drying of the sugar coating liquid is simultaneously performed. 'The sugar coating layer of the coated core material can be formed. As a device using the continuous coating method, for example, Hicoater (Freund Industries), Aqua coater (Freund Industries), Po wr ex coater (Powrex), Dri a coater (P o w r e x ), and the like can be exemplified. The droplet diameter of the spray coating liquid is preferably 0.1 to ι, 〇〇〇μηι, and the spray amount is adjusted according to the size or amount of the core material so as to be spread over the entire surface of the core material. Further, the temperature of the sugar coating liquid is preferably from 1 〇 to 8 〇 ° c. Regarding the temperature of the feed gas and the amount of the air, it is preferable to adjust the temperature of the product to 10 to 60 ° C. In the case of producing the sugar-coated granules, it is preferred to use a fluidized bed coating machine, in particular, a rotating fluidized bed coating machine having a rotating disk at the bottom is particularly preferred. For example, Multiplex (Powrex), Granurex (Freund Industries), Spir-A-Flow (Freund Industries), Agglomaster (Hosokawa Micron), New/Marumerizer (Fuj ipaudal), and the like. In the coating device for continuously rotating the bottom surface of the body, the particles containing the drug or the protective particles of the waterproof layer or the like are added, and the particles and the protective particles flowing and rotating in the device are simultaneously sprayed and dried by the sugar coating liquid. A sugar coating layer covering the core material is formed. The droplet diameter of the spray coating liquid is preferably 0.1 to 100 μm, and the amount of spray is adjusted according to the size or amount of the core material so as to be spread over the entire surface of the core material. Further, the temperature of the sugar coating liquid is preferably from 10 to 80 °C. The temperature of the feed gas and the amount of the air are adjusted so that the temperature of the product becomes 10 to 5 (TC is preferably -20-200812571. Further, the coating layer other than the coating liquid of the present invention can be used to form a coating system. The coating device to be used in this case can be appropriately selected and used depending on the type of the coating liquid, etc., and the amount of droplets or spray when the coating liquid is sprayed can be adjusted in the same manner as the spraying of the sugar coating liquid. The sugar-coated preparation of the present invention thus obtained has a thin sugar coating layer and a sufficient hardness as compared with the conventional preparation, and is also excellent in low hygroscopicity, odor resistance, and chipping property. The present invention will be specifically described. <Production Example 1> 3000 g of lactose, 150 g of hydroxypropylcellulose (HPC_L: Japan Soda), 1 200 g of corn starch, and 1000 g of crystalline cellulose (Cesolus PH-101: Asahi Kasei) were added. In a high-speed stirring granulator (VG-25: Powrex), fine water is added to prepare the granules, which are dried in a fluidized bed dryer (FLO-5B: Freund Industries). Machine (Power mill, Showa Chemical Machinery) granules the dried product. Mix 50g of magnesium stearate with 53 50g of the whole granules, and use it as a roller type ingot machine (HP-A18_SS: 畑铁工所) Manufactured as a 270 mg per ounce of ingot per liter. In 5400 g of the obtained ingot, hydroxypropylmethyl-21 - 200812571-based cellulose 2 910 (TC-5R: Shin-Etsu Chemical Co., Ltd.) A coated liquid of 900 g of purified water was applied to a plain layer by a coating machine (Dria coater DRC-650 'Powrex) to produce a 275 mg anti-g-ingot per 1 sharp. <Example 1 &gt; 5 500 g of the protective ingot obtained in Production Example 1 using 1180 g of white granulated sugar, 400 g of talc, 400 g of precipitated calcium carbonate, and 66.7 g of ethyl acrylate-methyl methacrylate copolymer 30% dispersion (Eutragit NE3 0D: Suspension coatings made of refined water from the Kawaguchi Chamber of Commerce and 200 g of purified water were dried by a coating machine (Dria coater DRC-650, Powrex) spray-coating solution to obtain 3 75 mg of sugar-coated tablets per ingot. The time taken for the covering operation was 2 hours. &lt;Example 2 &gt; Manufacturing Example 1 at 5 500 g For the protective ingot, use 1160 g of white granulated sugar, 400 g of talc, 400 g of precipitated calcium carbonate, 133.3 § ethyl acrylate·methyl methacrylate copolymer 30% dispersion (Eudragit NE30D: Sakaguchi Chamber of Commerce) and 2 The suspension coating liquid of 0 0 0 g of purified water was dried by a coating machine (Dria coater DRC - 65 0, Powrex) spray coating liquid to obtain a 375 mg sugar-coated tablet per one spindle. In addition, the time required for the covering operation is 2 hours. &lt;Example 3 &gt; -22- 200812571 In 5 500 g of the protective ingot obtained in Production Example 1, 1120 g of white granulated sugar, 400 g of talc, 400 g of precipitated calcium carbonate, and 266.7 g of ethyl acrylate·methacrylic acid were used. The suspension coating solution of the methyl ester copolymer 30% dispersion (Eudragit NE30D: Sakaguchi Chamber of Commerce) and 2000 g of purified water was dried by a coating machine (Dria coater DRC-650, Powrex) spray coating to obtain 1 tablet per spindle. It is a 3 75 mg sugar-coated tablet. In addition, the time required for the covering operation is 2 hours. &lt;Comparative Example 1 &gt; In 5 500 g of the protective ingot obtained in Production Example 1, 1160 g of white granulated sugar, 400 g of talc, 400 g of precipitated calcium carbonate, and 40 g of hydroxypropylmethylcellulose 2910 (TC-5R) were used. : Susukino Chemical Industry Co., Ltd. and 2000 g of purified water to obtain a suspension coating liquid, which was dried by a coating machine (Dria coater DRC - 65 0, Powrex) spray coating liquid to obtain a sugar-coated tablet of 3 75 mg per one. In addition, the time required for the covering operation is 2 hours. &lt;Comparative Example 2 &gt; In 5 500 g of the protective ingot obtained in Production Example 1, 1 924 g of white granulated sugar, 542 g of talc, 81 8 g of precipitated calcium carbonate, 64 g of gum arabic, 3 g of gelatin, 22 g were used. Polyethylene oxide (105) polypropylene oxide (5) ethylene glycol (PEP-101: Freund industry) and 1200g of refined water to form a suspension coating liquid to the coating machine (Dria coater DRC-650, Powrex The traditional sugar coating method of spraying, cooking, and drying the sugar coating liquid was carried out to obtain a sugar-coated tablet of 44 5 mg per one tablet. In addition, the time taken for the work to be covered by -23 - 200812571 is 6.5 hours. &lt;Production Example 2 &gt; Force U into 500 00 of garlic processed product (Oxoamidine, manufactured by Rigaku Chemical Co., Ltd.), 2500 g of lactose, 150 g of hydroxypropylcellulose (HPC-L: Japan Soda), 1200 g Corn starch, l〇〇〇g of crystalline cellulose (Ceolus PH-101: Asahi Kasei) was placed in a high-speed stirring granulator (乂〇 _ 25 : Powrex ), and refined water was added to prepare granules. After drying with a fluidized bed dryer (FLO-5B: Freund Industries), the dried product was granulated by a granulator (Power mill, Showa Chemical Machinery). 50 g of magnesium stearate was mixed with 53 50 g of the obtained whole granules. This was produced by a roller type ingot machine (HP-AP18-SS: 畑铁工所), and a 270 mg of ingot per one spindle was produced. In 5400 g of the obtained ingot, a coating liquid made of 100 g of hydroxypropylmethylcellulose 2910 (TC-5R: Shin-Etsu Chemical Industry) and 90 g of purified water was used as a coating machine (Dria coater). DRC—650, Powrex) is applied with a waterproof layer to the ingot to make a protective ingot of 2 75 mg per ingot. &lt;Example 4 &gt; In 5 5 00 g of the protective ingot obtained in Production Example 2, 1180 g of white granulated sugar, 400 g of talc, 40 g of precipitated calcium carbonate, and 66.7 g of ethyl acrylate·methyl methacrylate were used. The suspension of the copolymer 30% dispersion (Eudragit NE30D: 樋口商会) and 2000g of purified water was suspended -24-200812571 floating sugar coating liquid, dried with a coating machine (Dria coater DRC-650, Powrex) spray coating liquid to obtain each One ingot is 375 mg of sugar-coated sharp. In addition, the time required for the covering operation is 2 hours. &lt;Example 5&gt; In 5 500 g of the protective ingot obtained in Production Example 2, 1160 g of white granulated sugar, 400 g of talc, 400 g of precipitated calcium carbonate, and 133.3 g of ethyl acrylate·methyl methacrylate copolymer were used. A suspension of 30% dispersion (Eudragit NE3 0D: Sakaguchi Chamber of Commerce) and 200 00 g of purified water was dried by a coating machine (Dria coater DRC-650, Powrex) spray coating to obtain 3 per ingot. 75 mg of sugar-coated tablets. In addition, the time required for the covering operation is 2 hours. &lt;Example 6 &gt; In 5 500 g of the protective ingot obtained in Production Example 2, 1120 g of white granulated sugar, 400 g of talc, 400 g of precipitated calcium carbonate, and 266.7 g of ethyl acrylate·methyl methacrylate were used. The suspension of the 30% dispersion (Eudragit NE30D: Sakaguchi Chamber of Commerce) and 2000 g of purified water was dried by a coating machine (Dria coater DRC-650, Powrex) spray coating to obtain 1 per 1 The ingot is a 375 mg sugar-coated tablet. In addition, the time required for the covering operation is 2 hours. &lt;Comparative Example 3> In 5 500 g of the protective ingot obtained in Production Example 2, 1 160 g of 25-200812571 white granulated sugar, 400 g of talc, and sedative hydroxypropyl methylcellulose 2910 (TC- 5R · _ Shin-Etsu Chemical Industry Co., Ltd.) and 2000g of purified water-made suspension coating liquid's coating drying machine (Dria coater DRC 650, P owrex) spray coating liquid under the order of drying 'to get 3 sharp per 1 3 5 Mg sugar ingots. In addition, the time required for the covering operation is 2 hours. &lt;Comparative Example 4 &gt; φ In 5 500 g of the protective ingot obtained in Production Example 2, using 1,924 g of white granulated sugar, 542 g of talc, 818 g of precipitated calcium carbonate, 64 g of gum arabic, 30 g of gelatin, and 22 g of poly A suspension coating of ethylene oxide (105) polypropylene oxide (5) ethylene glycol (PEP-1 0 1 : Freund Industries) and 1 200 g of purified water to a coating machine (Dria coater DRC - 65 0 , P owrex ), a traditional sugar coating method of spraying, cooking and drying the sugar coating liquid, respectively, to obtain a sugar-coated tablet of 445111 § per ingot. In addition, the time taken for the covered work was 6.5 hours. &lt;Production Example 3&gt; The addition of 10 g of methionine acid (methylthioglycolic acid, Yonezawamycin), 600 g of lactose, and 300 g of polyvinylpyrrolidone (CoridonSO: BASF Japan), 1550 g of corn starch, 500 g of CarmeUose calcium (ECG-5 05: Wude Pharmaceuticals) were placed in a high-speed stirring granulator (VG-25: Powrex), and ethanol was added to prepare granules. After drying in a fluidized bed dryer (FLO-5B··Freund Industries), the dried product was granulated by a granulator (Power mill, Showa Chemical Machinery). -26- 200812571 Mix 50g of magnesium stearate with 390mg of whole granules, and use a roller type ingot machine (HP-AP18-SS: 畑铁工所) to make lOOmg per 1 spindle. Prime ingots. In 4000 g of the obtained ingot, 400 g of hardened oil, 100 g of glyceryl monostearate (Nikkol MGS-B: Nikko Chemical) and 100 g of polyethylene glycol monostearate (40EO) (NikkolMYS-40) were used. : Daylight Chemical) In a 600 mL ethanol solution and 200 g of talc, a water-repellent layer was applied to a sharp coating machine (Dria coater DRC-650, Powrex) to produce a protective ingot of 120 mg per ingot. &lt;Example 7&gt; In 4800 g of the protective ingot obtained in Production Example 3, a copolymer of 1180 g of white granulated sugar, 400 g of bone, 400 g of precipitated calcium carbonate, and 66.7 g of ethyl acrylate·methyl methacrylate was used. The suspension of the 30% dispersion (Eudragit NE30D: 樋口商会) and 2000 g of purified water was dried by a coating machine (Dria coater DRC-650, Powrex) spray coating to obtain each mirror. It is a 170 mg sugar-coated tablet. In addition, the time required for the covering operation is 1 hour. &lt;Example 8&gt; In 4 800 g of the protective ingot obtained in Production Example 3, 1160 g of white granulated sugar, 400 g of talc, 400 g of precipitated calcium carbonate, and 133.3 g of ethyl acrylate·methyl methacrylate copolymer were used. 30% dispersion (Eudragit NE30D: 樋口商会) and 2000g of refined water made of suspension -27- 200812571 floating sugar coating liquid, dried with a coating machine (Dria coater DRC - 650, Powrex) spray coating liquid to obtain 1 ingot It is a 70 mg sugar-coated tablet. In addition, the time required for the covering operation is 1 hour. &lt;Example 9&gt; The protective ingot obtained in Production Example 3 of 4 800 g was copolymerized with 1 120 g of white granulated sugar, 400 g of talc, 400 g of precipitated calcium carbonate, and 266.7 g of ethyl acrylate·methyl methacrylate. The suspension of the 30% dispersion (Eudragit NE30D: Sakaguchi Chamber of Commerce) and 2000 g of purified water was dried by a coating machine (Driacoater DRC - 65 0 'Powrex) spray coating to obtain 170 mg per ingot. Sugar coated ingots. In addition, the time required for the covering operation is 1 hour. &lt;Comparative Example 5 &gt; In 4 800 g of the protective ingot obtained in Production Example 3, 1160 g of white granulated sugar, 400 g of talc, 400 g of precipitated calcium carbonate, and 40 g of hydroxypropylmethylcellulose 2910 (TC-5R) were used. : Shin-Etsu Chemical Industry Co., Ltd. and 2000g of purified water to make the suspension coating liquid, which is dried by a coating machine (〇1^(:〇3161〇11€: — 65 0, P 〇wre X ) The amount of time required for the coating operation was 1 hour. The comparative example 6&gt; The protective ingot obtained in the production example 3 of 48 00 g was made of 6 〇 Og of white granulated sugar and 1100 g of talc. 1100g of precipitated calcium carbonate, 280g of A-28-200812571 Labo gum, 60g of gelatin and 600g of refined water to form a suspension coating liquid 'with coating machine (Dria coater DRC-650, Powrex)' A conventional sugar coating method of spraying, cooking, and drying was carried out to obtain a sugar-coated tablet of 200 mg per ingot. The time required for the coating operation was 3.5 hours. &lt;Production Example 4 &gt; 3300 g of sodium valproate and 165 g of light were added. The phthalic anhydride and 303.6 g of ethyl cellulose were stirred at high speed. A granulator (VG-25: Powrex) was added to ethanol to prepare granules, which was dried in a fluidized bed dryer (FL〇_5B: Freund Industries) and then granulated (Power mill, Showa Chemical Machinery). The dried product is granulated. The whole granule obtained by mixing 24 g of calcium stearate with 342 6 g is prepared by using a roller type ingot machine (HP-AP1 8-SS: 畑铁工所). 23 0 mg of bismuth ingot. In 3,220 g of the obtained ingot, dissolved and dispersed 6 〇g of ethyl cellulose, 30 g of methacrylic acid copolymer L (Eudragit L100: 樋口商会), 22.5 g of citric acid triethyl Ester and 22.5g of light oleic anhydride in 1365g of ethanol solution, using a coating machine (Dria coaterDRC - 650' Powrex) to release the control layer in the ingot, then use to dissolve, disperse 60g of ethyl cellulose and 3 〇g of light phthalic anhydride in 1410 g of ethanol solution, and a release control layer (Dria coater DRC-650, Powrex) was applied to release a control layer to produce a release control ingot of 245 mg per ingot. -29 - 200812571 &lt;Example 1&gt; The release control ingot obtained in Production Example 4 of 6 86 g, using white sugar, 3 g of slippery Stone, 51g of precipitated calcium carbonate, 9.9g of ethyl acrylate·methyl methacrylate copolymer 3〇% dispersed EudragitNE30D: 樋口商会) and 135.6g of refined water to make a floating sugar coating liquid, to cover machine (Hicoater HCT- 30N, Freund) was dried under a spray coating to obtain a sugar-coated tablet of 295 mg per 1 tablet (the mass of the coating layer was 5 Omg). In addition, the overlap between the jobs was 40 minutes. &lt;Example 1 1&gt; In 68 6 g of the production control ingot obtained in Production Example 4, white sugar, 6 g of talc, 102 g of precipitated calcium carbonate, and 20.1 g of ethyl acetate·methyl methacrylate were used. The copolymer was 30% dispersed with Eudragit NE30D: 樋口商会) and 270.9 g of purified water to obtain a floating sugar coating solution, which was dried by a coating machine (Hicoater HCT-30N, Freund) spray coating to obtain 3 45 mg per 1 tablet (the clothes thereof) The layer has a mass of l〇〇mg) of a sustained-release sugar-coated tablet. In addition, the time taken for the cover is 75 minutes. &lt;Comparative Example 7 &gt; The release control ingot obtained in Production Example 4 of 68 6g was made up to 2 8 8.6 g of white granulated sugar, 8 1 .3 g of talc, and 1 2 2.7 g of precipitated carbonic acid 9 · 6 g Acacia gum, 4 · 5 g of gelatin, 3.3 g of polyethylene oxide 93 g of enoic acid t (the suspension of sugar in the industry costs 186 g of propylene liquid (the suspension of sugar in the industry by calcium, -30 - ( 105 200812571 ) A suspension sugar coating liquid made of polypropylene oxide (5) ethylene glycol and 180 g of purified water, and a traditional sugar coating of the sugar coating liquid sprayed, cooked and dried by a small sugar-coated machine (made by Kikusui Seisakusho Co., Ltd.) The method 'requires a powdered ingot of 41 5 mg per ingot. The time required for the coating operation is 300 minutes. Further, a suspension icing made of 114 g of white granulated sugar, 6 g of titanium oxide and 72 g of purified water is used. A small sugar-coated machine (made by Kikusui Seisakusho Co., Ltd.) was used to spray, retort, and dry the sugar-coating liquid, respectively, to obtain a color coat of 45 5 mg per ingot. 240 minutes. Finally, use 15g of white sugar and 9g of refined The sugar-coated liquid was prepared by a small sugar-coated machine (made by Kikusui Seisakusho Co., Ltd.), which was sprayed, cooked, and dried, respectively, to obtain a coating of 460 mg (one of which has a sugar coating layer of 215 mg). In addition, the time required for the covering operation was 30 minutes, and the total time required for all the covering operations was 570 minutes. From the above results, it was found that the manufacturing method of the present invention using simultaneous spraying and drying of the coating liquid and the conventional coating method In comparison, it is possible to shorten the working time by one third or less. Further, it is also known that the weight of the sugar coating layer in the sugar-coated tablet may be one-half to one-fourth of a degree. <Evaluation of hygroscopicity> Example 1 to 9, the sugar-coated tablets obtained in Comparative Examples 1 to 6 were ingots, and the mass after standing for 1 hour, 2 hours, 3 hours, and 24 hours was measured under the conditions of 25 ° C to 84.3%, and the quality at the beginning was performed. For comparison, the moisture absorption amount was measured to calculate the moisture absorption rate (%). Further, the sugar-coated ingots obtained in Examples 10 to 1 1 and Comparative Examples 7 to 31 200812571 were subjected to the conditions of 40 ° C - 7 5 %. 'Measurement for 3 hours, 1 day, 2 The moisture absorption rate (%) was calculated in the same manner as above for the masses of 3 days, 7 days, 10 days, 14 days, 21 days, 28 days, and 3 days. The results are shown in Figures 1 to 4. (%) = (1 barium ingot mass after each time of storage - 1 bardle tablet mass at the beginning) / 10 spindle masses at the beginning xl 00 According to Figure 1, the sugar coating formulations of Examples 1 to 3 Even after standing for 24 hours under the above conditions, the moisture absorption rate was low, being 1%. When the sugar-coating preparation of Comparative Example 1 was allowed to stand for 3 hours, the moisture absorption rate was 0.2%, and when it was allowed to stand for 24 hours, the moisture absorption rate was increased to nearly 1.2%. Further, when the sugar-coating preparation of Comparative Example 2 was allowed to stand for 24 hours, the moisture absorption rate was increased to about 0.5%. According to Fig. 2, the sugar-coating preparations of Examples 4 to 6 were allowed to stand for 24 hours under the above conditions, and the moisture absorption rate was as low as 0.1%. When the sugar-coating preparation of Comparative Example 3 was allowed to stand for 3 hours, the moisture absorption rate was 0.4%, and when it was allowed to stand for 24 hours, the moisture absorption rate was increased to nearly 2.1%. Further, when the sugar-coating preparation of Comparative Example 4 was allowed to stand for 24 hours, the moisture absorption rate was increased to about 0.5%. According to Fig. 3, the sugar-coated preparations of Examples 7 to 9 and Comparative Example 6 were allowed to stand for 24 hours under the above conditions, and the moisture absorption rate was as low as 0.5% or less. When the sugar-coated preparation of Comparative Example 5 was allowed to stand for 3 hours, the moisture absorption rate increased to nearly 1.3%, and when it was left to stand for 24 hours, it increased to nearly 5.6%. According to Fig. 4, in the sugar-coated preparations of Examples 10 and 11, even if the quality of the sugar-coated layer was about 1/1 and 1/1 of that of Comparative Example 7, the moisture absorption rate after 30 days was extremely low. , respectively, 2.0% and 1.0%. In contrast, in the sugar-coated preparation of Comparative Example 7, the rate of moisture absorption -32-200812571 was nearly 4.0% at the stage after 7 days, and further, after 10 days, the tablet was broken. It is speculated that the tablet breakage is due to the hygroscopicity of sodium valproate. From the above, it can be seen that when the sugar coating liquid of the present invention is used, even when the sugar coating preparation is produced by a coating method of drying under a sugar coating liquid, an excellent sugar-soluble preparation having low hygroscopicity can be obtained as compared with the conventional sugar coating preparation. &lt;Evaluation of physical properties&gt; The hardness and degree of collapse of the sugar-coated tablets obtained in Examples 1 to 9 and Comparative Examples 1 to 6 were measured. In the hardness, 20 spindles were used, and the hardness of the tablet was measured for each tablet in a tablet hardness tester (ΡΤΒ-311Ε manufactured by PHARMATEST Co., Ltd.) to calculate the average enthalpy. The degree of ablation was measured by a subsidy plate according to the collapse test method described in the 15th revision of the Japan Pharmacopoeia (Toyama Industrial Co., Ltd. collapse tester). The test was carried out on 6 spindles to calculate the average enthalpy. The results are shown in Tables 1 to 3. [Table 1] Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Hardness (N) 120.2 148.6 116.1 71.6 142.7 Degree of collapse (parts) 22.4 21.0 20.6 29.9 30.9 The sugar coating preparations of Examples 1 to 3 were sufficient. The hardness is also excellent in collapse. On the other hand, the sugar coating preparation of Comparative Example i was insufficient in hardness and collapse. The sugar-coated preparation of Comparative Example 2 had high hardness but was insufficient in collapse. -33- 200812571 [Table 2] Table 2 Example 4 Example 5 Example 6 Comparative Example 3 Comparative Example 4 Hardness (N) 118.5 120.3 125.8 91.8 138.5 Degree of collapse (parts) 20.5 22.3 21.9 28.3 32.1 Examples 4 to 6 The sugar-coated preparation had sufficient hardness and was excellent in collapse property. On the other hand, the sugar:coating preparation of Comparative Example 3 was insufficient in hardness and collapse property. Comparing the sugar of Example 4; although the night preparation has high hardness, it is insufficient in collapse. [Table 3] Table 3 Example 7 Example 8 Example 9 Comparative Example 5 Comparative Example 6 Hardness (N) 72.8 76.5 81.8 59.8 92.9 Degree of collapse (parts) 12.1 11.5 12.2 11.9 18.5 The sugar-coated preparations of Examples 7 to 9 have It has sufficient hardness and is excellent in collapse property. On the other hand, the sugar coating preparations of Comparative Examples 5 and 6 were insufficient in hardness and collapse property. From the above, it is understood that the sugar-coated preparation of the present invention has sufficient hardness and is excellent in collapse property. &lt;Evaluation of Odor&gt; The odor of the sugar-coated tablets obtained in Examples 4 to 9 and Comparative Examples 3 to 6 was evaluated. After sealing the obtained preparation in a transparent glass bottle, at 60 ° C, the odor generated when stored for 3 days, 1 week or 2 weeks, 〇: completely -34- 200812571 did not feel the unpleasant smell from the drug Taste, 1: almost no unpleasant odor from the drug, 2: feeling: unpleasant odor from the drug, 3: strong feeling: a 4-stage evaluation of the unpleasant odor from the drug sputum. The evaluation is conducted by 5 people: line, and the average value of f is calculated. The results are shown in Tables 4 to 5. [Table 4] Table 4 Example 4 Example 5 Example 6 Comparative Example 3 Comparative Example 4 Immediately after manufacture 0 0 0 0 0 After 3 days 0 0 0 1.2 0 After 1 week 0 0 0 2.6 0 After 2 weeks 0 0 0 3.0 0 The sugar-coated preparations of Examples 4 to 6 and Comparative Example 4 did not feel the unpleasant odor from Oxoami dine at all during the storage period of 2 weeks. In another aspect, the sugar-coated preparation of Comparative Example 3 strongly felt the unpleasant odor from Oxoam i dine. In particular, it is understood that the unpleasant odor becomes stronger as the storage is longer. [Table 5] Table 5 __一^-- Example 7 Example 8 Example 9 Comparative Example 5 Comparative Example 6 - Immediately after manufacture 0 0 0 0 0 After 3 days 0 0 0 2.2 0 After 1 week 0.4 0.4 0.6 3.0 1.2 After 2 weeks 1.2 1.4 1.4 3.0 1.4 The sugar-coated preparations of Examples 7 to 9 and Comparative Example 6 did not feel the unpleasant odor from MMSC at all during the storage period of 2 weeks. On the other hand, in the case of -35-200812571, the sugar-coated preparation of Comparative Example 5 felt an unpleasant odor from MMSC after 3 days, and an unpleasant odor was strongly felt after 1 week. From the above, it is understood that the sugar-coated preparation of the present invention is superior in deodorizing property as compared with the conventional sugar-coated preparation. &lt;Evaluation of moisture 刚 immediately after manufacture&gt; Examples 7 to 9 after pulverization: The sugar-coated tablets of Comparative Examples 5 to 6 were weighed and taken up to about 5 g, and calcium hydroxide was used as a reaction reagent, and it was measured by a barometric moisture meter. In 〇 minutes, the moisture 値 (%) was calculated. The results are shown in Table 6. [Table 6] Table 6____Example 7 Example 8 Example 9 Comparative Example 5 Comparative Example β Moisture 値 (%) 1.65_L55_L62_L56_2.48 The sugar-coated preparations of Examples 7 to 9 and Comparative Example 5 The moisture 値 (%) was lower than that of the sugar coating preparation of Comparative Example 6. Therefore, it has been found that when the continuous coating method is used, the moisture enthalpy in the tablet can be reduced as compared with the conventional coating method. &lt;Dissolution test&gt; The dissolution test of the sugar-coated tablet of Example 1 was carried out. The test was carried out according to the second method (refrigeration) method of the Pharmacy Dissolution Test Method of the Pharmacy, and the second liquid of the 500% test of the general test method collapse test was used as the test liquid at 10 rpm. The sodium valproate content in the sample solution was quantified by HPLC, and the dissolution rate (%) of sodium valproate was calculated. The result is shown in Figure 5 of _ 36 - 200812571. As is clear from Fig. 5, the sugar-coated preparation of the present invention is also excellent in sustained release property. According to the above, the sugar coating liquid of the present invention is effectively used for the formulation of a sugar coating which requires a sustained release drug. As described above, the sugar-coated preparation of the present invention is produced by a continuous coating method, and has a sufficient hardness as compared with a conventional sugar-coated preparation, and is excellent in low hygroscopicity and odor-reducing property, and is coated by a sugar coating method. The conventional sugar-coated preparation produced can be produced by a short-time coating operation, and has a low moisture content after production and an excellent disintegration property. In other words, according to the production method of the present invention, even if the sugar coating layer is thin, it has sufficient hardness, and it is possible to produce low moisture content, low moisture absorption property, collapse property, and odor resistance immediately after production in a short time and in a simple manner. Sugar coating preparation. [Industrial Applicability] Using the sugar coating liquid of the present invention, a sugar coating preparation can be produced by simultaneously performing a spraying step of a sugar coating liquid and a continuous coating method of a drying step. In other words, it is possible to produce a sugar-coated preparation having low oxygen permeability, low moisture absorption, odor resistance, and collapse property in a short period of time without complicated steps. Further, since the production method of the present invention can form a thin sugar-coated layer, it greatly contributes to the reduction in the amount of the sugar-coating liquid used and the miniaturization of the preparation. [Simplified description of the drawings] [Fig. 1] shows the change in moisture absorption rate of the elapsed time and the sugar coating preparation. Fig. 2 is a graph showing the change in moisture absorption rate of -37-200812571 of the elapsed time and the sugar-coated preparation containing the garlic processed product. Fig. 3 is a graph showing changes in moisture absorption rate of elapsed time and a sugar-coated preparation containing MMSC. Fig. 4 is a graph showing changes in the moisture absorption rate of the elapsed time and the sugar-coated preparation containing sodium valproate. Fig. 5 is a graph showing the elapsed time and the change in the dissolution rate of sodium valproate.

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Claims (1)

200812571 X. Application for Patent Park 1. A sugar coating liquid, a sugar coating solution containing sugar, ethyl acrylate, methyl propyl acetonate copolymer and solvent, characterized by ethyl acrylate·methyl methacrylate copolymer The concentration is 0.01 to 10% by weight based on the total solids. 2 - a sugar-coated preparation having a drug-containing core material and a sugar coating preparation covering the sugar coating layer of the core material, characterized in that at least one layer of the sugar coating layer contains 0.01 to 10% by weight of sugar and ethyl acrylate • Methyl methacrylate copolymer. · 3. A sugar-coated preparation as claimed in claim 2, which further has a release control layer. 4. A sugar-coated preparation according to item 2 or item 3 of the patent application, wherein the medicine is a drug having an unpleasant odor, a drug which is unstable to moisture, or a drug which generates whiskers. 5 - A method for producing a sugar-coated preparation, characterized in that the spraying step of the sugar-coating liquid as in the first application of the patent scope, and the drying step - 39 -