HK1138514A - Cysteine odor-reduced solid preparation - Google Patents

Description

Solid preparation with reduced cysteine odor

Technical Field

The present invention relates to a solid preparation with reduced cysteine odor. More particularly, to an envelope preparation in which the odor of cysteine is reduced.

Background

Solid preparations containing L-cysteine cannot be taken directly because of the strong unpleasant odor of L-cysteine itself. As the most common method for masking such unpleasant odor, a solid preparation is coated with a water-soluble polymer such as hydroxypropyl cellulose, hydroxypropyl methylcellulose, or polyvinylpyrrolidone as a base material, but since these coatings cannot mask the odor of cysteine, the coating is further coated with a sugar coating to form a very dense coating film to mask the odor of cysteine. However, since the step of forming a sugar coating is not only time-consuming and large-sized and heavy-weight preparations, but also the step is in a high-temperature and high-humidity state, the stability, appearance, and the like of other active ingredients coexisting are affected by moisture, incomplete temperature control, and the like in the production process.

Therefore, in order to reduce the unpleasant odor of L-cysteine in solid preparations, a method of making a thin sugar-coated tablet (patent document 1), a method of incorporating L-cysteine having a specific particle size by a dry method (patent document 2), a method of incorporating an acidulant and a sweetener (patent document 3), a method of coating ethyl cellulose and incorporating an acidulant and a sweetener (patent document 4), a method of incorporating carboxymethyl cellulose or a salt thereof (patent document 5), a method of incorporating a water-swellable substance (patent document 6), and the like have been proposed. However, the method of producing a thin sugar-coated tablet has a problem that a step of forming a sugar coating is required even if the odor of cysteine is masked, and the other methods have a problem that the effect of removing odor is insufficient.

Patent document 1: japanese patent laid-open No. 2002-179559

Patent document 2: japanese patent laid-open No. 2003-155232

Patent document 3: japanese patent application laid-open No. 2004-161700

Patent document 4: japanese patent application laid-open No. 2004-161701

Patent document 5: japanese patent laid-open No. 2005-162619

Patent document 6: japanese patent laid-open No. 2005-298528

Disclosure of The Invention

The invention aims to provide a solid preparation containing L-cysteine, which has short manufacturing time, can realize the miniaturization of the preparation and has reduced unpleasant smell.

The present inventors have conducted extensive studies to achieve the above object and have unexpectedly found that when a solid preparation containing L-cysteine is coated with a coating film containing a partially saponified product of polyvinyl alcohol, the unpleasant odor of L-cysteine can be reduced even without further coating with a sugar coating, thereby completing the present invention.

That is, the present invention provides a solid preparation comprising L-cysteine or a salt thereof, which is coated with a coating film comprising a partially saponified product of polyvinyl alcohol.

The invention makes it possible to obtain a solid preparation containing L-cysteine, which has reduced unpleasant odor even without coating with a sugar coating. In addition, the preparation of the present invention can be made compact, and therefore, it is easy to swallow and can be produced in a short time.

Best Mode for Carrying Out The Invention

The molecular formula of the L-cysteine (chemical name: 2-amino-3-mercaptopropionic acid) used in the invention is C₃H₇NO₂S has a molecular weight of 121.16, and functions as an SH donor in a metabolic system in vivo or as an SH enzyme activator. As a medical drug, it is used for the treatment of various skin diseases such as eczema, urticaria, drug eruptions, toxic eruptions, acne vulgaris, erythema exudativum multiforme and the like or the treatment of leukopenia caused by radiation damage, by the normalization of skin metabolism of L-cysteine, antiallergic action, detoxification action and the like. As a common pharmaceutical product, a vitamin main drug preparation, a calcium main drug preparation, a health care preparation containing vitamins, and the like are incorporated, and the pharmaceutical composition is widely used for the treatment of pigmentation such as chloasma, freckles, sunburn, and the like, general fatigue, hangover, acne, eczema, urticaria, contact dermatitis, drug eruptions, pachylosis, stomatitis, angular stomatitis, cheilitis, glossitis, dermatitis, and erosion, and other various treatments such as nourishing and strengthening (physical weakness, physical fatigue, after illness, anorexia, malnutrition, fever consumptive disease, nutrition replenishment in cases of prenatal and postpartum, and the like), bleeding prevention (gum bleeding, epistaxis), and the like.

L-cysteine or a salt thereof (hereinafter referred to as "L-cysteine") used in the present invention may, in addition to the aforementioned L-cysteine, be an L-cysteine addition salt such as L-cysteine hydrochloride. In the present invention, any 1 of them may be used, and L-cysteine is preferred.

The content of L-cysteine in the solid preparation varies depending on the presence or absence of other active ingredients coexisting, the amount of the other active ingredients blended, and the dosage form, and for example, 1 to 80% by mass of the tablet, and 1 to 100% by mass of the granule or fine granule are preferable.

In the preparation of the present invention, other medicinal ingredients may be appropriately incorporated in addition to L-cysteine. Specific examples of the other active ingredients include vitamin C such as ascorbic acid, calcium ascorbate and sodium ascorbate, vitamin B such as thiamine nitrate, thiamine hydrochloride, riboflavin butyrate, riboflavin sodium phosphate, pyridoxine hydrochloride, pyridoxal phosphate, calcium pantothenate, nicotinamide, biotin and folic acid, vitamin-like substance such as lipoamide and orotic acid, vitamin E such as D-alpha-tocopheryl acetate and D-alpha-tocopheryl succinate, vitamin D such as calciferol and cholecalciferol, mineral such as calcium hydrogen phosphate and calcium lactate, amino acid such as methionine, glycine and arginine hydrochloride, amino acid such as taurine, glucuronolactone, glycyrrhizic acid and ursodeoxycholic acid, liver-disorder drug such as polygonum multiflorum extract, crataegus pinnatifida extract, acanthopanax senticosus dry extract, epimedium extract, and epimedium extract, Crude drugs such as Coicis semen extract, liver hydrolysate, bile extract powder, bupleuri radix dry extract, rhizoma Ligustici Chuanxiong dry extract, fructus crataegi dry extract, and Poria dry extract.

Examples of the partially saponified product of polyvinyl alcohol used in the present invention include partially saponified products of polyvinyl alcohol obtained by hydrolyzing polyvinyl acetate, and partially saponified products of modified anionized polyvinyl alcohol obtained by modifying a part of polyvinyl alcohol with a carboxyl group, a sulfonyl group, or the like.

The saponification degree of the partially saponified product of polyvinyl alcohol is preferably 70 to 97 mol%, particularly preferably 78 to 96 mol%, from the viewpoint of the effect of reducing the odor of cysteine. Further, the average polymerization degree is preferably 200 to 3300, particularly preferably 300 to 1500. Here, the degree of saponification can be measured in accordance with JIS K6726 (polyvinyl alcohol test method).

Examples of commercially available products of these polyvinyl alcohols include ゴ - セノ - ル (Nippon synthetic chemical Co., Ltd.), J-Boval (Nippon vinyl acetate-Boval (Ox. ビ - ポバ - ル) Co., Ltd.), クラレ Boval (Kolar (クラレ) Co., Ltd.), and デンカ Boval (electrochemical Co., Ltd.). In addition, a premix containing polyvinyl alcohol as a main component, for example, commercially available from japan as opadry AMB (オパドライ AMB, japan karaoke (カラコン) corporation), may also be used. They may be used alone or in combination of 2 or more.

The content of polyvinyl alcohol in the coating film is preferably 30 to 100% by mass, particularly preferably 40 to 95% by mass, from the viewpoint of the effect of preventing odor, the film strength and the ease of coating.

In addition to the partially saponified product of polyvinyl alcohol, the coating film may be optionally added with, for example, a plasticizer, a coating agent, a dispersant, a colorant, an antifoaming agent, and other pharmaceutical additives commonly used in coating films of oral pharmaceuticals.

Specific examples of the plasticizer include カリオン 83, triethyl citrate, glycerin fatty acid ester, sesame oil, a dimethylpolysiloxane-silica mixture, D-sorbitol, medium-chain triglycerides, a sugar alcohol solution of corn starch, triacetin, concentrated glycerin, castor oil, diethyl phthalate, dibutyl phthalate, butyl phthalyl butyl glycolate, polyoxyethylene (105) polyoxypropylene (5) glycol, propylene glycol, polysorbate 80, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000, a mixture of cottonseed oil and soybean oil, and glycerin monostearate, and these may be used alone or in combination of 2 or more. The content of the plasticizer in the coating film is preferably 30% by mass or less, particularly preferably 25% by mass or less.

Specific examples of the coating agent include, in addition to a partially saponified product of polyvinyl alcohol, a dispersion of an ethyl acrylate-methyl methacrylate copolymer, an acetyl glycerin fatty acid ester, an aminoalkyl methacrylate copolymer E, an aminoalkyl methacrylate copolymer RS, gum arabic powder, ethyl cellulose, an aqueous dispersion of ethyl cellulose, octyldecyl triglyceride, Opadry-6950, Opadry-S-7135, Opadry-S-8471, Opadry-S-9607, Opadry-S-22829, Opadry-S-22835, Opadry-S-22961, olive oil, kaolin, cacao butter, Prunellae Spica, castor wax, caramel, carnauba wax, carbopol, carboxymethyl ethyl cellulose, sodium carboxymethyl starch, sodium, Carboxymethylcellulose calcium, carboxymethylcellulose sodium, hydrous silicon dioxide, dried aluminum hydroxide gel, dried milky white shellac, dried methacrylic acid copolymer LD, wintersweet powder, fish scale foil, gold foil, silver foil, triethyl citrate, glycerin fatty acid ester, magnesium silicate, light anhydrous silicic acid, hydroxypropyl cellulose containing light anhydrous silicic acid, light liquid paraffin, spermaceti wax, microcrystalline cellulose, hardened oil, synthetic aluminum silicate, synthetic wax, high dextrose syrup, hard wax, succinylated gelatin, wheat flour, wheat starch, rice starch, cellulose acetate, vinyl acetate resin, cellulose acetate phthalate, white wax, titanium oxide, magnesium oxide, dimethylaminoethyl methacrylate-methyl methacrylate copolymer, dimethylpolysiloxane (for internal use), dimethylpolysiloxane-silicon dioxide mixture, sodium hydroxide, sodium, Gypsum Fibrosum Preparatum, sucrose fatty acid ester, lignum Aquilariae Resinatum powder, aluminum hydroxide gel, hydrogenated rosin glyceride, stearyl alcohol, stearic acid, aluminum stearate, calcium stearate, polyoxyl stearate 40, magnesium stearate, refined gelatin, refined shellac, refined white sugar, zein, sorbitan sesquioleate, cetyl alcohol, Gypsum Fibrosum, gelatin, shellac, sorbitan fatty acid ester, D-sorbitol solution, tricalcium phosphate, pulvis Talci, calcium carbonate, magnesium carbonate, simple syrup, gold silver foil (Japanese original: middle gold foil), precipitated calcium carbonate, low-substitution hydroxypropyl cellulose, terpene resin, starch (soluble), corn syrup, corn oil, glyceryl triacetate, calcium lactate, lactose, concentrated glycerol, white shellac, white sugar, honey, paraffin wax, pearl powder, potato starch, hydroxypropyl cellulose, Hydroxypropyl methylcellulose 2208, hydroxypropyl methylcellulose 2906, hydroxypropyl methylcellulose 2910, hydroxypropyl methylcellulose acetate succinate, hydroxypropyl methylcellulose 2910, titanium oxide polyethylene glycol 400 mixture, hydroxypropyl methylcellulose phthalate, piperonyl butoxide, castor oil, diethyl phthalate, dibutyl phthalate, butyl phthalyl butyl glycolate, glucose, fumaric acid stearic acid polyvinyl acetal diethylaminoacetate hydroxypropyl methylcellulose 2910 mixture, pullulan, propylene glycol, bentonite, povidone, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene (105) polyoxypropylene (5) diol, polyoxyethylene (160) polyoxypropylene (30) diol, polysorbate 80, polyvinyl acetal diethylaminoacetate, and the like, Polyethylene glycol 300, polyethylene glycol 400, polyethylene glycol 600, polyethylene glycol 1500, polyethylene glycol 1540, polyethylene glycol 4000, polyethylene glycol 6000, polyethylene glycol 20000, polyethylene glycol 35000, D-mannitol, syrup, beeswax, myristyl alcohol, anhydrous silicic acid hydrate, phthalic anhydride, anhydrous calcium hydrogen phosphate, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, magnesium metasilicate aluminate, methyl cellulose, 2-methyl-vinylpyridine methacrylate-methacrylic acid copolymer, wood wax, aluminum monostearate, glyceryl monostearate, sorbitan monolaurate, montanate wax, medicinal charcoal, lauromacrogol, calcium sulfate, liquid paraffin, DL-malic acid, calcium hydrogen phosphate, sodium hydrogen phosphate, calcium dihydrogen phosphate, rosin and the like, which may be added alone, or adding more than 2 kinds of the above materials. In these coating agents, talc is preferably added from the viewpoint of the anti-adhesion effect. The content of the coating agent in the coating film is preferably 1 to 50% by mass, particularly preferably 5 to 40% by mass.

Specific examples of the dispersant include aminoalkyl methacrylate copolymer RS, gum arabic, acacia powder, propylene glycol alginate, ethanol, oleic acid, carbopol, sodium carboxymethylcellulose, agar powder, citric acid, sodium citrate, glycerin fatty acid ester, magnesium silicate, light anhydrous silicic acid, microcrystalline cellulose, hardened oil, synthetic aluminum silicate, choline phosphate, safflower oil, white wax, titanium oxide, dioctyl sodium sulfosuccinate, sucrose fatty acid ester, sodium hydroxide, stearic acid, magnesium stearate, refined oleic acid, refined soybean lecithin, sorbitan sesquioleate, sorbitan fatty acid ester, D-sorbitol, soybean oil, soybean lecithin, low-substituted hydroxypropylcellulose, dextrin, corn starch, tragacanth powder, sorbitan trioleate, lactose, concentrated glycerin, Potato starch, hydroxyethyl cellulose, hydroxypropyl starch, hydroxypropyl cellulose, hydroxypropyl methylcellulose 2910, propylene glycol fatty acid ester, bentonite, povidone, polyoxyethylene hydrogenated castor oil 40, polyoxyethylene hydrogenated castor oil 60, polyoxyethylene (105) polyoxypropylene (5) diol, polyoxyethylene (160) polyoxypropylene (30) diol, polysorbate 20, polysorbate 60, polysorbate 80, sodium polyphosphate, polyethylene glycol 300, polyethylene glycol 4000, polyethylene glycol 6000, anhydrous sodium citrate, anhydrous sodium pyrophosphate, magnesium metasilicate, sodium metaphosphate, methyl cellulose, wood wax, sorbitan monooleate, aluminum monostearate, glycerol monostearate, sorbitan monopalmitate, sorbitan monolaurate, sodium lauryl sulfate, polylauryl alcohol, Liquid paraffin, calcium hydrogen phosphate, etc., which can be added singly or in combination of more than 2 kinds. The content of the dispersant in the coating film is preferably 25% by mass or less, particularly preferably 15% by mass or less.

Specific examples of the coloring agent include Axiandaning (Japanese original: アセンヤクタンニン) powder, turmeric extract, yellow triiron dioxide, オパスプレ -K-1-24904, orange essence, brown iron oxide, carbon black, caramel, carmine, carotene solution, beta-carotene, licorice extract, gold foil, black iron oxide, light anhydrous silicic acid, titanium oxide, ferric oxide, edible blue No. 1, edible yellow No. 4 aluminum lake, edible yellow No. 5, edible red No. 2, edible red No. 3, edible red No. 102, sodium hydroxide, talc, sodium copper chlorophyll, extract of rye green leaf, d-borneol, myristyl dodecate, medicinal charcoal, riboflavin butyrate, riboflavin, green tea powder, riboflavin sodium phosphate, rose oil, etc., they may be added singly or in admixture of 2 or more. The content of the colorant in the coating film is preferably 35% by mass or less, particularly preferably 25% by mass or less.

Specific examples of the defoaming agent include ethanol, glycerin fatty acid ester, dimethylpolysiloxane (for internal use), dimethylpolysiloxane-silica mixture, sucrose fatty acid ester, silicone resin emulsion, silicone defoaming agent, polyoxyl stearate 40, sorbitan fatty acid ester, sorbitan trioleate, and polysorbate 80, and these may be added singly or in admixture of 2 or more. The content of the defoaming agent in the coating film is preferably 10% by mass or less, particularly preferably 2% by mass or less.

The preparation of the present invention is a coated solid preparation obtained by coating a preparation containing L-cysteine with a coating film containing a partially saponified product of polyvinyl alcohol. The dosage form of the solid preparation may, for example, be a tablet, a granule, a fine granule or the like, and particularly preferably a tablet. Further, these tablets, granules and fine granules may be coated with a coating film containing a partially saponified product of polyvinyl alcohol, and the coating film may be filled into hard capsules or soft capsules to form capsules.

The preparation of the present invention can be produced by coating a preparation containing L-cysteine or crystals of L-cysteine with a coating film containing a partially saponified product of polyvinyl alcohol. The method for producing a solid preparation is not particularly limited, and a preparation can be prepared by a conventionally known conventional method by blending L-cysteine and other pharmaceutically active ingredients used as needed, and adding a preparation additive as needed.

Examples of the pharmaceutical additives used for formulating solid preparations include carriers acceptable in the pharmaceutical field, for example, excipients, binders, disintegrants, disintegration aids, lubricants, fluidizers, glossing agents, foaming agents, moisture-proofing agents, surfactants, stabilizers, emulsifiers, antioxidants, fillers, preservatives, sweeteners, flavors, cooling agents, perfuming agents, flavors, and colorants.

Specific examples of the additives for the preparation include lactose, white sugar, mannitol, xylitol, dextrin, sorbitol, erythritol, reduced maltose syrup, pullulan, povidone, cellulose, microcrystalline vitamin, low-substituted hydroxypropyl cellulose, methyl cellulose, hydroxypropyl cellulose, polyethylene glycol, propylene glycol, polyoxyethylene polyoxypropylene glycol, croscarmellose sodium, crospovidone, starch, gelatinized starch, carboxymethylcellulose calcium, ethyl cellulose, carboxymethyl starch, fumaric acid, citric acid, stearic acid, magnesium stearate, calcium stearate, talc, light anhydrous silicic acid, silicon dioxide, sucrose fatty acid ester, polyoxyethylene (105) polyoxypropylene (5) glycol, titanium oxide, sodium edetate, propyl gallate, calcium lactate, calcium carbonate, and the like, Conventionally known additives for solid preparations such as precipitated calcium carbonate, calcium silicate, calcium hydrogen phosphate, magnesium aluminate metasilicate, gelatin, gum arabic, carnauba wax, white wax, aminoalkyl methacrylate copolymer E, polyvinyl acetal diethylaminoacetate, polyoxyethylene polyoxypropylene glycol, dimethylpolysiloxane, glycerin fatty acid ester, medium-chain fatty acid triglyceride, succinylated gelatin, glycerin, hardened oil, caramel, riboflavin sodium phosphate, ferric oxide, red No. 102, yellow No. 5, and the like.

When it is necessary to prepare a powder for use in the production of tablets, granules and fine granules, it can be produced by a conventional granulation method, for example, a wet granulation method such as spray granulation using a solution or dispersion containing water or an organic solvent, a stirring granulation method, a fluidized granulation method, a rolling granulation method or a rolling fluidized granulation method, or a dry granulation method such as compacting granulation using a powder binder. When tablets are prepared, the tablets are prepared by mixing raw powder, fine granules, granules and preparation additives, and then carrying out compression molding.

The coating method of coating the solid preparation with a coating film containing a partially saponified polyvinyl alcohol is not particularly limited, and examples thereof include pan coating, fluidized bed coating, roll coating, dry coating, and a combination thereof. For example, a coating solution is prepared by dissolving and suspending a partially saponified product of polyvinyl alcohol and a coating composition containing a plasticizer, a coating agent, a dispersant, a colorant, an antifoaming agent, and the like as necessary in purified water heated as necessary, and the coating is performed on the preparation by a conventional method at the time of coating. The coating solution is prepared so that the solid content is usually 1 to 50% by mass, particularly preferably 2 to 30% by mass.

In the present invention, the thickness of the coating film layer formed on the solid preparation varies depending on the form of the solid preparation, the quality, shape and coating amount thereof, and is preferably 5 μm or more, more preferably 10 to 2000 μm, particularly preferably 20 to 1000 μm, and further more preferably 20 to 500 μm. For example, in order to obtain the thickness of the coating layer, it is preferable that the coating is applied to tablets having a diameter of about 9mm and a mass of about 200mg, and it is preferable that the coating is applied to tablets at a thickness of 5 μm, 2.3mg and 20 μm, and 4.6mg and 20 μm, respectively.

The dose of the preparation of the present invention is appropriately selected depending on the body weight, age, sex, type of disease and symptoms of a patient, and for adults, the dose of L-cysteine administered as a medical drug is 160 to 480mg per 1 day, and the dose of L-cysteine administered as a general drug is preferably 30 to 240mg per 1 day. The number of administration is preferably 1 to 3 times per day.

The coated solid preparation obtained as described above can reduce the odor of L-cysteine which cannot be reduced by the conventional method and coating, and does not generate an offensive odor with time even after being filled in an airtight container such as a glass bottle or PTP package. Further, the coated solid preparation of the present invention does not require a step of coating with a sugar coating, and therefore, the preparation can be miniaturized and the production cost can be reduced, and the time for which the preparation is exposed to a high-temperature and high-humidity state is short, so that the discoloration of the preparation can be prevented while maintaining the stability of the pharmaceutical ingredients.

The present invention will be specifically described below with reference to examples, but the present invention is not limited thereto.

Example 1

[ production of plain sheet ]

1600g of L-cysteine (manufactured by concerted fermentation), 3280g of lactose, 2400g of microcrystalline cellulose, 1000g of low-substitution hydroxypropylcellulose, 40g of light anhydrous silicic acid, 40g of magnesium stearate and 40g of talc were used to prepare a powder for tableting by a conventional method, and the obtained mixed powder was tabletted with a punch rod (Japanese text: pestle) of 9mm phi using a rotary tablet press (VIRGO-0512 type tablet press manufactured by Chrysanthemum water), to obtain about 8kg of plain tablets each having a mass of 210mg and a thickness of 4 mm.

[ production of envelope sheet ]

A coating solution obtained by dissolving 160G of a partially saponified product of polyvinyl alcohol (type G ゴ - セノ - ル GL-05: degree of saponification: 86.5-89.0, manufactured by Nippon synthetic chemical Co., Ltd.) and 40G of talc in 1800G of purified water was used, and 1kg of the above-mentioned plain film was coated with a coating machine (ハイコ - タ -HCT-30N, Freund (フロイント) industry) to increase the mass of each plain film by 5mg to obtain a coated film of the present invention. The film thickness at this time was 21.3 μm (average value of n measured by image analysis, 20).

The coated tablets (30) thus obtained were packed in a No. 5 glass standard bottle and sealed with a stopper to conduct an odor test, and no generation of an unpleasant odor was observed after 12 months of storage at room temperature and 6 months of storage at 40 ℃. On the other hand, as a result of an odor test in which 30 of the above-mentioned plain tablets were put into a No. 5 glass standard bottle and tightly closed with a stopper, generation of a bad odor was observed both after 12 months of storage at room temperature and after 6 months of storage at 40 ℃.

Comparative example 1: manufacture of ordinary coated tablets

A coated sheet of the present invention was obtained by coating 1kg of the plain sheet obtained in example 1 with a coating machine (ハイコ - タ -HCT-30N, Freund industries) using a coating solution prepared by dissolving 150g of hydroxypropylmethylcellulose 2910(TC-5RW, manufactured by shin-Etsu chemical Co., Ltd.), 10g of polyethylene glycol 6000 (manufactured by Nippon fat Co., Ltd.), and 40g of talc in 1800g of a suspension in a solvent (ethanol: purified water: 3: 7), and increasing the mass of each plain sheet by 5 mg. The thickness of the film at this time was 39.7 μm (average value of n 20 measured by image analysis).

The coated tablets were packed in a No. 5 glass standard bottle and sealed with a stopper to conduct an odor test, and as a result, generation of an unpleasant odor was observed after 12 months of storage at room temperature or 6 months of storage at 40 ℃.

Example 2: manufacture of wrapping sheet

In the same manner as in example 1, 1kg of the plain tablets obtained in example 1 was coated so that the mass of each plain tablet was increased by 2.5mg to obtain coated tablets of the present invention. The film thickness at this time was 10.2 μm (average value of n measured by image analysis, 20).

The coated tablets (30) thus obtained were packed in a No. 5 glass standard bottle and sealed with a stopper to conduct an odor test, and no generation of an unpleasant odor was observed after 12 months of storage at room temperature and 6 months of storage at 40 ℃.

Example 3: manufacture of wrapping sheet

In the same manner as in example 1, 1kg of the plain tablets obtained in example 1 was coated to increase the mass of each plain tablet by 1.3mg, thereby obtaining coated tablets of the present invention. The film thickness at this time was 5.1 μm (average value of n measured by image analysis 20).

The coated tablets (30) thus obtained were packed in a No. 5 glass standard bottle and sealed with a stopper to conduct an odor test, and no generation of an unpleasant odor was observed after 12 months of storage at room temperature and 6 months of storage at 40 ℃.

Example 4: manufacture of wrapping sheet

In the same manner as in example 1, 1kg of the plain tablets obtained in example 1 was coated so that the mass of each plain tablet was increased by 7.5mg to obtain coated tablets of the present invention. The film thickness at this time was 31.3 μm (average value of n measured by image analysis 20).

The coated tablets (30) thus obtained were packed in a No. 5 glass standard bottle and sealed with a stopper to conduct an odor test, and no generation of an unpleasant odor was observed after 12 months of storage at room temperature and 6 months of storage at 40 ℃.

Example 5: manufacture of wrapping sheet

In the same manner as in example 1, 1kg of the plain tablets obtained in example 1 was coated with a film so that the mass of each plain tablet was increased by 10mg, thereby obtaining coated tablets of the present invention. The film thickness at this time was 40.9 μm (average value of n measured by image analysis 20).

The coated tablets (30) thus obtained were packed in a No. 5 glass standard bottle and sealed with a stopper to conduct an odor test, and no generation of an unpleasant odor was observed after 12 months of storage at room temperature and 6 months of storage at 40 ℃.

Example 6

[ production of plain sheet ]

Using 400g of L-cysteine (manufactured by concerted fermentation), 250g of ascorbic acid, 250g of pyridoxine hydrochloride, 200g of nicotinamide, 190g of riboflavin sodium phosphate, 50g of thiamine nitrate, 0.5g of biotin, 5g of corn starch, 424.5g of microcrystalline cellulose, 200g of hydroxypropyl cellulose, 110g of low-substitution hydroxypropyl cellulose, 10g of magnesium stearate, and 10g of talc, powders for tableting were prepared by a conventional method, and the resulting mixed powder was tableted with a 9mm phi punch pin using a rotary tablet press (VIRGO-0512 type tablet press: manufactured by JUHUISHU Co., Ltd.) to obtain about 1.9kg of plain tablets each having a mass of 210mg and a thickness of 4 mm.

[ production of envelope sheet ]

The mass of each of the plain tablets was increased by 7mg by coating 1kg of the plain tablet with a coating solution prepared by dissolving 400g of opadry AMB white (オパドライ AMB ホワイト, manufactured by kokara (カラコン) japan) in 1600g of purified water and coating the resultant solution with a coating machine (ハイコ - タ -HCT-30N, freunds industries), thereby obtaining a coated tablet of the present invention. The film thickness at this time was 30.8 μm (average value of n measured by image analysis 20).

The coated tablets (30) thus obtained were packed in a No. 5 glass standard bottle and sealed with a stopper to conduct an odor test, and no generation of an unpleasant odor was observed after 12 months of storage at room temperature and 6 months of storage at 40 ℃.

Claims (4)

1. A coated solid preparation characterized in that a solid preparation containing L-cysteine or a salt thereof is coated with a coating film containing a partially saponified product of polyvinyl alcohol.

2. The coated solid preparation according to claim 1, wherein the coating film has a thickness of 5 μm or more.

3. The coated solid preparation according to claim 1, wherein the polyvinyl alcohol has a saponification degree of 70 to 97 mol%.

4. The coated solid preparation according to any one of claims 1 to 3, wherein the coating film further contains 1 or more selected from the group consisting of a plasticizer, a coating agent, a dispersant, a colorant and an antifoaming agent.