JP6154758B2 - Dry syrup - Google Patents
Dry syrup Download PDFInfo
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- JP6154758B2 JP6154758B2 JP2014017418A JP2014017418A JP6154758B2 JP 6154758 B2 JP6154758 B2 JP 6154758B2 JP 2014017418 A JP2014017418 A JP 2014017418A JP 2014017418 A JP2014017418 A JP 2014017418A JP 6154758 B2 JP6154758 B2 JP 6154758B2
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- carbocysteine
- sodium
- dry syrup
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- mixed
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
- A61K31/198—Alpha-aminoacids, e.g. alanine, edetic acids [EDTA]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/10—Expectorants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/12—Mucolytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
Description
本発明は、L−カルボシステインの酸味を軽減させ、処方や携帯に便利で、そのままでも、あるいは水に懸濁または溶解して服用することができるドライシロップ剤に関するものである。 The present invention relates to a dry syrup that reduces the acidity of L-carbocysteine, is convenient for prescription and carrying, and can be taken as it is or suspended or dissolved in water.
L−カルボシステインは気道粘膜に含まれる各種ムチンの含量比を正常化し、粘液の粘度を低下させる。また、線毛細胞などの粘膜上皮を修復することにより、粘液線毛輸送系を改善し、貯留物の排泄を促進する。これらの作用から本剤は、各種呼吸器疾患の去痰、慢性副鼻腔炎の排膿、滲出性中耳炎の排液に優れた効果が認められている。
L−カルボシステインの製剤としては錠剤、細粒剤、懸濁シロップ剤、シロップ剤がある。
L-carbocysteine normalizes the content ratio of various mucins contained in the airway mucosa and lowers the viscosity of the mucus. In addition, by repairing mucosal epithelium such as ciliated cells, the mucociliary transport system is improved and the excretion of the reservoir is promoted. Based on these actions, this drug has been found to be effective for expectoration of various respiratory diseases, drainage of chronic sinusitis, and drainage of exudative otitis media.
L-carbocysteine preparations include tablets, fine granules, suspension syrups, and syrups.
一般的にシロップ剤のような液剤は、固形製剤と比較して薬局や病院等での調剤業務に手間がかかるうえ、患者が携帯するのにも不便である。一方、固形製剤では、嚥下能力の弱い小児や高齢者にとって服用させるのが困難である。このような点を改良し、より服用性に優れ、処方や携帯にも便利な製剤の開発は望まれるところである。
またL−カルボシステインは強い酸味を有するため、この酸味の軽減にはL−カルボシステインに対して多量の糖類を添加するか、またはL−カルボシステインを含んだ顆粒にコーティングなど特殊な加工を施す必要があった。そのため、多量の糖類を添加した製剤では、製造や包装コストが増す上、一回の服用量が多くなり、服用、調剤業務、携帯の際に不便であった。また、コーティングを施した製剤では、製造工程の複雑化と製造コストが増大するという医療経済上の問題がある。
In general, liquid preparations such as syrups are inconvenient for a patient to carry, as well as being troublesome in dispensing operations at pharmacies and hospitals as compared to solid preparations. On the other hand, solid preparations are difficult to take for children and elderly people with weak swallowing ability. It is desired to develop a preparation that improves such points and is more excellent in ingestion and convenient for prescription and carrying.
In addition, since L-carbocysteine has a strong acidity, to reduce the acidity, a large amount of saccharide is added to L-carbocysteine, or a granule containing L-carbocysteine is subjected to special processing such as coating. There was a need. For this reason, preparations containing a large amount of saccharide increase the production and packaging costs, and increase the dose at one time, which is inconvenient for taking, dispensing, and carrying. In addition, the preparation with coating has a medical economic problem that the manufacturing process becomes complicated and the manufacturing cost increases.
本発明者らは、L−カルボシステインを含んだ顆粒にコーティングなど特殊な加工をせずに、より簡便な製造工程でL−カルボシステインの酸味を軽減させ、服用、調剤ならびに携帯に便利で、水に懸濁して容易に服用することができるドライシロップ剤を完成させた。
すなわち、本発明は糖アルコール、高甘味度甘味剤、並びにクロスポビドン、カルメロース、及びカルメロースナトリウムからなる群より選ばれる1種又は2種以上の成分を配合することで、コーティングなど特殊な加工をする必要のない簡便な製造工程によってL−カルボシステインの酸味の軽減を達成したドライシロップ製剤を提供するものである。
このようにして得られたL−カルボシステインのドライシロップ剤は、調剤業務が比較的容易に行え、携帯する上にも便利で、用時水に懸濁して服用でき、なおかつ小児から高齢者まで服用可能な製剤である。
The present inventors reduce the acidity of L-carbocysteine in a simpler production process without special processing such as coating on granules containing L-carbocysteine, and are convenient for taking, dispensing and carrying, A dry syrup that can be easily taken by suspending in water was completed.
That is, the present invention combines sugar alcohol, a high-intensity sweetener, and one or more components selected from the group consisting of crospovidone, carmellose, and carmellose sodium to perform special processing such as coating. The present invention provides a dry syrup preparation that achieves a reduction in the acidity of L-carbocysteine by a simple production process that does not need to be performed.
The dry syrup of L-carbocysteine thus obtained can be dispensed relatively easily, is convenient to carry, can be suspended in water during use, and can be taken from children to the elderly. It is a possible formulation.
本発明に用いられる糖アルコールとは、糖分子のカルボニル基を還元して得られる多価アルコールである。例えば、マンニトール、ソルビトール、マルチトール、粉末還元麦芽糖水アメ、エリスリトール、キシリトールなどが挙げられる。これらの糖アルコールは2種以上を用いてもよい。 The sugar alcohol used in the present invention is a polyhydric alcohol obtained by reducing a carbonyl group of a sugar molecule. Examples thereof include mannitol, sorbitol, maltitol, powdered reduced maltose water candy, erythritol, xylitol and the like. Two or more of these sugar alcohols may be used.
本発明に用いられる高甘味度甘味剤とは、ショ糖の10倍以上の甘味度を有する甘味剤である。例えば、アスパルテーム、サッカリン及びその塩類、グリチルリチン酸及びグリチルリチン酸二カリウム等のグリチルリチン酸の塩類、アセスルファムカリウム、ステビアなどが挙げられる。これらの高甘味度甘味剤は2種以上を用いてもよい。 The high-intensity sweetener used in the present invention is a sweetener having a sweetness level 10 times or more that of sucrose. Examples include aspartame, saccharin and salts thereof, glycyrrhizic acid and glycyrrhizic acid salts such as dipotassium glycyrrhizinate, acesulfame potassium, stevia and the like. Two or more kinds of these high-intensity sweeteners may be used.
本発明における製造方法としては特に限定はなく、流動層造粒法、攪拌造粒法、高速攪拌造粒法、転動流動層造粒法、乾式造粒法など公知のいかなる方法を用いても製造することができる。 The production method in the present invention is not particularly limited, and any known method such as fluidized bed granulation method, stirring granulation method, high speed stirring granulation method, rolling fluidized bed granulation method, and dry granulation method may be used. Can be manufactured.
尚、本発明においては、服用性や商品的価値をさらに高めることを目的として、任意に結合剤や賦形剤、崩壊剤、着香剤、滑沢剤、着色剤などの医薬品添加物を配合することができる。これらの添加剤は1種又は2種以上であってもよい。 In the present invention, pharmaceutical additives such as binders, excipients, disintegrants, flavoring agents, lubricants, and coloring agents are optionally added for the purpose of further enhancing the ingestion and commercial value. can do. These additives may be used alone or in combination of two or more.
任意に配合しうる結合剤としては、医薬品添加物として用い得るものであれば特に制限はない。例えば、ポリビニルピロリドン(PVP)、ヒドロキシプロピルセルロース(HPC)、ヒドロキプロピルメチルセルロース(HPMC)、アラビアゴム末、ポリビニルアルコール、メチルセルロース、ゼラチン、プルラン等を挙げることができる。これらは2種以上であってもよい。好ましい当該結合剤としては、ポリビニルピロリドン、ヒドロキシプロピルセルロースを挙げることができる。 The binder that can be optionally blended is not particularly limited as long as it can be used as a pharmaceutical additive. For example, polyvinyl pyrrolidone (PVP), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), gum arabic powder, polyvinyl alcohol, methyl cellulose, gelatin, pullulan and the like can be mentioned. Two or more of these may be used. Preferred examples of the binder include polyvinyl pyrrolidone and hydroxypropyl cellulose.
任意に配合しうる崩壊剤としては、医薬品添加物として用い得るものであれば特に制限はない。当該崩壊剤は、本発明に関わるドライシロップを懸濁液として調製した際に、L−カルボシステインの分散性を高める懸濁化剤としての働きを有する。例えば、結晶セルロース、ヒドロキシプロピルスターチ、カルメロース、カルメロースカルシウム、カルメロースナトリウム、バレイショデンプン、トウモロコシデンプン、低置換度ヒドロキシプロピルセルロース、クロスポピドン、クロスカルメロースナトリウム、カルボキシメチルスターチナトリウム等を挙げることができる。これらは2種以上であってもよい。好ましい当該崩壊剤としては、クロスポピドン、クロスカルメロースナトリウム、カルボキシメチルスターチナトリウムを挙げることができる。 There are no particular limitations on the disintegrant that can be optionally blended as long as it can be used as a pharmaceutical additive. The disintegrant acts as a suspending agent that enhances the dispersibility of L-carbocysteine when the dry syrup according to the present invention is prepared as a suspension. Examples thereof include crystalline cellulose, hydroxypropyl starch, carmellose, carmellose calcium, carmellose sodium, potato starch, corn starch, low-substituted hydroxypropylcellulose, crospovidone, croscarmellose sodium, carboxymethyl starch sodium, and the like. . Two or more of these may be used. Preferred disintegrants include crospovidone, croscarmellose sodium, and sodium carboxymethyl starch.
任意に配合しうる着香剤としては、医薬品添加物として用い得るものであれば特に制限はない。例えば、オレンジエキス、オレンジ油、オレンジエッセンス、スペアミント油、ハッカ油、バニラフレーバー、レモン油、l−メントール、ピーチフレーバー、グレープフルーツフレーバー、ストロベリーエッセンス等を挙げることができる。 The flavoring agent that can be optionally blended is not particularly limited as long as it can be used as a pharmaceutical additive. Examples include orange extract, orange oil, orange essence, spearmint oil, peppermint oil, vanilla flavor, lemon oil, l-menthol, peach flavor, grapefruit flavor, strawberry essence and the like.
任意に配合しうる滑沢剤としては、医薬品添加物として用い得るものであれば特に制限はない。例えば、含水二酸化ケイ素、トウモロコシデンプン、ショ糖脂肪酸エステル、ステアリン酸及びその塩類、フマル酸、フマル酸ステアリルナトリウム、タルク、ポリエチレングリコール等を挙げることができる。 The lubricant that can be optionally blended is not particularly limited as long as it can be used as a pharmaceutical additive. Examples thereof include hydrous silicon dioxide, corn starch, sucrose fatty acid ester, stearic acid and its salts, fumaric acid, sodium stearyl fumarate, talc, polyethylene glycol and the like.
任意に配合しうる着色剤としては、医薬品添加物として用い得るものであれば特に制限はない。例えば、三二酸化鉄、黄色三二酸化鉄、カラメル、等を挙げることができる。 The colorant that can be optionally blended is not particularly limited as long as it can be used as a pharmaceutical additive. For example, iron sesquioxide, yellow iron sesquioxide, caramel, etc. can be mentioned.
本発明に関わるドライシロップを懸濁液、または溶解液として調製する際にL−カルボシステインの溶解性をさらに高めることを目的として、任意に可溶化剤の医薬品添加物を配合することができる。 When the dry syrup according to the present invention is prepared as a suspension or solution, a solubilizer pharmaceutical additive can be optionally blended for the purpose of further enhancing the solubility of L-carbocysteine.
任意に配合しうる可溶化剤としては、医薬品添加物として用い得るものであれば特に制限はない。例えば、無水クエン酸ナトリウム、クエン酸ナトリウム、水酸化ナトリウム、炭酸水素ナトリウム、炭酸水素ナトリウム、リン酸水素ナトリウム、無水リン酸二ナトリウム、リン酸三ナトリウム等を挙げることができる。これらは2種以上であってもよい。
また場合により、安息香酸ナトリウム、デヒドロ酢酸ナトリウム、ソルビン酸カリウム等の医薬品添加物として用い得る保存剤を添加することができる。さらには部分アルファー化デンプン等の賦形剤を配合することもできる。
The solubilizer that can be optionally blended is not particularly limited as long as it can be used as a pharmaceutical additive. For example, anhydrous sodium citrate, sodium citrate, sodium hydroxide, sodium hydrogen carbonate, sodium hydrogen carbonate, sodium hydrogen phosphate, anhydrous disodium phosphate, trisodium phosphate and the like can be mentioned. Two or more of these may be used.
In some cases, preservatives that can be used as pharmaceutical additives such as sodium benzoate, sodium dehydroacetate, and potassium sorbate can be added. Furthermore, excipients such as partially pregelatinized starch can be blended.
以下参考例により本発明を説明するが、本発明はこれらの参考例によって限定されるものではない。 The present invention will be described below with reference examples, but the present invention is not limited to these reference examples.
L−カルボシステイン250gに粉末還元麦芽糖水アメ402g、クロスカルメロースナトリウム37.5g、カルボキシメチルスターチナトリウム15g、安息香酸ナトリウム3g、アスパルテーム11.25g、黄色三二酸化鉄0.5gをとり混合した後、ヒドロキシプロピルセルロース11.25gを95%エタノールに溶解した液を112.5g加えて、スピードニーダー(NSK−250型、岡田精工社製)により混練した後,ペレッター(EXKS−1型、不二パウダル社製)により押し出し造粒した。得られた造粒物を通気乾燥機(30C型、不二パウダル社製)で乾燥し、目開き500μmの篩で整粒し顆粒を得た。この顆粒に含水二酸化ケイ素15gとグレープフルーツフレーバー0.75gを加えて混合し、ドライシロップ剤を得た。 L-carbocysteine 250 g was mixed with powdered reduced maltose water candy 402 g, croscarmellose sodium 37.5 g, sodium carboxymethyl starch 15 g, sodium benzoate 3 g, aspartame 11.25 g, yellow iron sesquioxide 0.5 g, 112.5 g of a solution obtained by dissolving 11.25 g of hydroxypropyl cellulose in 95% ethanol was added and kneaded with a speed kneader (NSK-250 type, manufactured by Okada Seiko Co., Ltd.), and then a pelleter (EXKS-1 type, Fuji Powder Co., Ltd.) And granulated by extrusion. The obtained granulated product was dried with a ventilation dryer (30C type, manufactured by Fuji Powder Co., Ltd.) and sized with a sieve having an opening of 500 μm to obtain granules. To this granule, 15 g of hydrous silicon dioxide and 0.75 g of grapefruit flavor were added and mixed to obtain a dry syrup preparation.
L−カルボシステイン250gに粉末還元麦芽糖水アメ450g、エリスリトール200.75g、クロスカルメロースナトリウム37.5g、カルボキシメチルスターチナトリウム15g、安息香酸ナトリウム3g、サッカリンナトリウム2.5g、グリチルリチン酸二カリウム5g、黄色三二酸化鉄0.5gをとり混合した後、ヒドロキシプロピルセルロース11.25gを95%エタノールに溶解した液を112.5g加えて、スピードニーダー(NSK−250型、岡田精工社製)により混練した後,ペレッター(EXKS−1型、不二パウダル社製)により押し出し造粒した。得られた造粒物を通気乾燥機(30C型、不二パウダル社製)で乾燥し、目開き500μmの篩で整粒し顆粒を得た。この顆粒に含水二酸化ケイ素20gとグレープフルーツフレーバー1gを加えて混合し、ドライシロップ剤を得た。 L-carbocysteine 250 g, powdered reduced maltose water candy 450 g, erythritol 200.75 g, croscarmellose sodium 37.5 g, carboxymethyl starch sodium 15 g, sodium benzoate 3 g, saccharin sodium 2.5 g, dipotassium glycyrrhizinate, yellow three After taking 0.5 g of iron dioxide and mixing, 112.5 g of a solution obtained by dissolving 11.25 g of hydroxypropylcellulose in 95% ethanol was added and kneaded by a speed kneader (NSK-250 type, manufactured by Okada Seiko Co., Ltd.) Extrusion granulation was performed with a pelleter (EXKS-1 type, manufactured by Fuji Powder Corporation). The obtained granulated product was dried with a ventilation dryer (30C type, manufactured by Fuji Powder Co., Ltd.) and sized with a sieve having an opening of 500 μm to obtain granules. To this granule, 20 g of hydrous silicon dioxide and 1 g of grapefruit flavor were added and mixed to obtain a dry syrup preparation.
L−カルボシステイン750gに粉末還元麦芽糖水アメ1197g、クロスカルメロースナトリウム112.5g、カルボキシメチルスターチナトリウム45g、安息香酸ナトリウム9gをとり混合した後、ヒドロキシプロピルセルロース33.75g、黄色三二酸化鉄1.5gを95%エタノールに溶解した液を400g加えて、ハイスピードミキサー(FSGS−5型、深江工業社製)により攪拌し造粒した。得られた造粒物を通気乾燥機(30C型、不二パウダル社製)で乾燥し、目開き500μmの篩で整粒し顆粒を得た。この顆粒に部分アルファー化デンプン45gとオレンジエッセンス22.5g、アスパルテーム33.75gを加えて混合し、ドライシロップ剤を得た。 After 1750 g of powdered reduced maltose water candy, 112.5 g of croscarmellose sodium, 45 g of sodium carboxymethyl starch, and 9 g of sodium benzoate were mixed with 750 g of L-carbocysteine, 33.75 g of hydroxypropyl cellulose and yellow iron sesquioxide 1. 400 g of a solution obtained by dissolving 5 g in 95% ethanol was added, and the mixture was stirred and granulated with a high speed mixer (FSGS-5 type, manufactured by Fukae Kogyo Co., Ltd.). The obtained granulated product was dried with a ventilation dryer (30C type, manufactured by Fuji Powder Co., Ltd.) and sized with a sieve having an opening of 500 μm to obtain granules. To this granule, 45 g of partially pregelatinized starch, 22.5 g of orange essence and 33.75 g of aspartame were added and mixed to obtain a dry syrup preparation.
L−カルボシステイン1750gに粉末還元麦芽糖水アメ2793g、クロスカルメロースナトリウム262.5g、カルボキシメチルスターチナトリウム105g、安息香酸ナトリウム21gをとり混合した後、ヒドロキシプロピルセルロース78.75g、黄色三二酸化鉄3.5gを70%エタノールに溶解した液を952g加えて、ハイスピードミキサー(FS−20型、深江工業社製)により攪拌し造粒した。得られた造粒物をフローコーター(FLO−15型、フロイント産業社製)で乾燥し、目開き500μmの篩で整粒し顆粒を得た。この顆粒に部分アルファー化デンプン105gとオレンジ油5.25g、アスパルテーム78.75gを加えて混合し、ドライシロップ剤を得た。 2750 g of powdered reduced maltose water candy, 262.5 g of croscarmellose sodium, 105 g of sodium carboxymethyl starch, and 21 g of sodium benzoate were mixed with 1750 g of L-carbocysteine, and then mixed with 78.75 g of hydroxypropylcellulose and yellow iron sesquioxide 3. 952 g of a solution obtained by dissolving 5 g in 70% ethanol was added, and the mixture was stirred and granulated with a high speed mixer (FS-20 type, manufactured by Fukae Kogyo Co., Ltd.). The obtained granulated product was dried with a flow coater (FLO-15 type, manufactured by Freund Sangyo Co., Ltd.) and sized with a sieve having an opening of 500 μm to obtain granules. To this granule, 105 g of partially pregelatinized starch, 5.25 g of orange oil, and 78.75 g of aspartame were added and mixed to obtain a dry syrup.
L−カルボシステイン4000gに粉末還元麦芽糖水アメ6504g、クロスカルメロースナトリウム600g、カルボキシメチルスターチナトリウム240g、安息香酸ナトリウム48gをとりフローコーター(FLO−15型、フロイント産業社製)内で流動化させ、ヒドロキシプロピルセルロースの3%水溶液を6000g噴霧し造粒した。得られた造粒物をフローコーター(FLO−15型、フロイント産業社製)内で乾燥した後、目開き500μmの篩で整粒し顆粒を得た。この顆粒に部分アルファー化デンプン240gとオレンジ油12g、アスパルテーム180gを加えて混合し、ドライシロップ剤を得た。 L-carbocysteine 4000 g, powdered reduced maltose water candy 6504 g, croscarmellose sodium 600 g, carboxymethyl starch sodium 240 g, and sodium benzoate 48 g were fluidized in a flow coater (FLO-15, manufactured by Freund Sangyo Co., Ltd.) 6000 g of a 3% aqueous solution of hydroxypropylcellulose was sprayed and granulated. The obtained granulated product was dried in a flow coater (FLO-15 type, manufactured by Freund Sangyo Co., Ltd.) and then granulated with a sieve having an opening of 500 μm to obtain granules. To this granule, 240 g of partially pregelatinized starch, 12 g of orange oil and 180 g of aspartame were added and mixed to obtain a dry syrup.
L−カルボシステイン1000gに粉末還元麦芽糖水アメ1596g、クロスカルメロースナトリウム150g、カルボキシメチルスターチナトリウム60g、安息香酸ナトリウム12g、ヒドロキシプロピルセルロース45g、部分アルファー化デンプン60g、オレンジ油3g、アスパルテーム45gを加えて混合した後、ローラーコンパクター(MINI型、フロイント産業社製)で圧縮成型し、平板状フレークを得た。このフレークをロールグラニュレーター(CRN−TS54型、日本グラニュレーター社製)で解砕した後に目開き500μmの篩で整粒しドライシロップ剤を得た。 Add 1596 g of powdered reduced maltose water candy, 150 g of croscarmellose sodium, 60 g of sodium carboxymethyl starch, 12 g of sodium benzoate, 45 g of hydroxypropylcellulose, 60 g of partially pregelatinized starch, 3 g of orange oil and 45 g of aspartame to 1000 g of L-carbocysteine After mixing, compression molding was performed with a roller compactor (MINI type, manufactured by Freund Corporation) to obtain flat plate-like flakes. The flakes were pulverized with a roll granulator (CRN-TS54 type, manufactured by Nippon Granulator Co., Ltd.) and then sized with a sieve having an opening of 500 μm to obtain a dry syrup agent.
L−カルボシステイン15600gに粉末還元麦芽糖水アメ19032g、クロスカルメロースナトリウム2340g、カルボキシメチルスターチナトリウム936g、安息香酸ナトリウム187.2g、三二酸化鉄31.2gをとり混合した後、ヒドロキシプロピルセルロース499.2gを80%エタノールに溶解した液を7435g加えて、ハイスピードミキサー(FS−GS100型、深江工業社製)により攪拌し造粒した。得られた造粒物をフローコーター(MTT−200F型、フロイント産業社製)で乾燥し、目開き500μmの篩で整粒し顆粒を得た。この顆粒に無水クエン酸ナトリウム1653.6g、粉末還元麦芽糖水アメ4680g、部分アルファー化デンプン936g、ストロベリーエッセンス3.12g、アスパルテーム936gを加えて混合し、ドライシロップ剤を得た。 L-carbocysteine 15600 g was mixed with powdered reduced maltose water candy 19032 g, croscarmellose sodium 2340 g, sodium carboxymethyl starch 936 g, sodium benzoate 187.2 g, and iron sesquioxide 31.2 g, and then mixed with hydroxypropyl cellulose 499.2 g. 7435 g of a solution in 80% ethanol was added, and the mixture was stirred and granulated with a high speed mixer (FS-GS100 type, manufactured by Fukae Kogyo Co., Ltd.). The obtained granulated product was dried with a flow coater (MTT-200F type, manufactured by Freund Sangyo Co., Ltd.) and sized with a sieve having an opening of 500 μm to obtain granules. To this granule, 1653.6 g of anhydrous sodium citrate, 4680 g of powdered reduced maltose water candy, 936 g of partially pregelatinized starch, 3.12 g of strawberry essence, and 936 g of aspartame were added and mixed to obtain a dry syrup preparation.
L−カルボシステイン178gに粉末還元麦芽糖水アメ155.6g、クロスカルメロースナトリウム50g、無水リン酸水素二ナトリウム118g、無水クエン酸ナトリウム53g、デヒドロ酢酸ナトリウム45g、ソルビン酸カリウム14g、三二酸化鉄0.4g,含水二酸化ケイ素270gをとりフローコーター(FBG−1型、フロイント産業社製)内で流動化させ、L−カルボシステイン322g、水酸化ナトリウム74gを水304gに溶解した液を噴霧した後、ポリビニルアルコール(部分けん化物)52g、カラメル3gを水465gに溶解した液を噴霧し造粒した。得られた造粒物をフローコーター(FBG−1型、フロイント産業社製)内で乾燥し顆粒を得た。この顆粒にトウモロコシデンプン94gとストロベリーエッセンス0.5g、アスパルテーム30g、グリチルリチン酸二カリウム10gを加えて混合しドライシロップ剤を得た。 178 g of L-carbocysteine, 155.6 g of powdered reduced maltose water candy, 50 g of croscarmellose sodium, 118 g of anhydrous disodium hydrogen phosphate, 53 g of anhydrous sodium citrate, 45 g of sodium dehydroacetate, 14 g of potassium sorbate, 0. 4 g and 270 g of hydrous silicon dioxide were taken and fluidized in a flow coater (FBG-1 type, Freund Sangyo Co., Ltd.). After spraying 322 g of L-carbocysteine and 74 g of sodium hydroxide in 304 g of water, polyvinyl A solution obtained by dissolving 52 g of alcohol (partially saponified product) and 3 g of caramel in 465 g of water was sprayed and granulated. The obtained granulated product was dried in a flow coater (FBG-1 type, manufactured by Freund Corporation) to obtain granules. To this granule, 94 g of corn starch, 0.5 g of strawberry essence, 30 g of aspartame, and 10 g of dipotassium glycyrrhizinate were added and mixed to obtain a dry syrup preparation.
L−カルボシステイン15600gに粉末還元麦芽糖水アメ19032g、クロスカルメロースナトリウム2340g、カルボキシメチルスターチナトリウム936g、安息香酸ナトリウム187.2g、三二酸化鉄31.2gをとり混合した後、ヒドロキシプロピルセルロース499.2gを70%エタノールに溶解した液を7625g加えて、ハイスピードミキサー(FS−GS100型、深江工業社製)により攪拌し造粒した。得られた造粒物をフローコーター(MTT−200F型、フロイント産業社製)で乾燥後、篩過整粒し顆粒を得た。この顆粒に無水クエン酸ナトリウム1653.6g、粉末還元麦芽糖水アメ4680g、部分アルファー化デンプン936g、ピーチフレーバー46.8g、アスパルテーム936gを加えて混合し、ドライシロップ剤を得た。 L-carbocysteine 15600 g was mixed with powdered reduced maltose water candy 19032 g, croscarmellose sodium 2340 g, sodium carboxymethyl starch 936 g, sodium benzoate 187.2 g, and iron sesquioxide 31.2 g, and then mixed with hydroxypropyl cellulose 499.2 g. Was added to 7625 g of 70% ethanol and stirred with a high speed mixer (FS-GS100, manufactured by Fukae Kogyo Co., Ltd.) for granulation. The obtained granulated product was dried with a flow coater (MTT-200F type, manufactured by Freund Sangyo Co., Ltd.) and sieved to obtain granules. To this granule, 1653.6 g of anhydrous sodium citrate, 4680 g of powdered reduced maltose water candy, 936 g of partially pregelatinized starch, 46.8 g of peach flavor, and 936 g of aspartame were added and mixed to obtain a dry syrup preparation.
(試験例1)
L−カルボシステイン、糖アルコール及び高甘味度甘味剤を以下の配合比で混合した対照製剤と参考例1〜9の製剤について味及び服用性について検討した。各々製剤試料を10%のL−カルボシステインを含むように水に懸濁して試験液とした。この液を健康成人に服用させ、味の官能試験を行った。その結果を表1および2に示した。
本試験結果からL−カルボシステインに糖アルコール及び高甘味度甘味剤を併用することで、味の良い服用性の優れたドライシロップ剤が得られることが見出された。
(Test Example 1)
Taste and ingestion were examined for a control preparation in which L-carbocysteine, sugar alcohol and high-intensity sweetener were mixed at the following blending ratio and the preparations of Reference Examples 1 to 9. Each preparation sample was suspended in water so as to contain 10% L-carbocysteine to prepare a test solution. This solution was taken by healthy adults and subjected to a taste sensory test. The results are shown in Tables 1 and 2.
From this test result, it was found that a dry syrup preparation with good taste and excellent ingestibility can be obtained by using L-carbocysteine in combination with a sugar alcohol and a high-intensity sweetener.
(試験例2)
参考例3、4、5、6及び9で得られた本発明によるドライシロップ剤について、それぞれ1.5gを、ポリエチレンテレフタレート、アルミニウムから成る包装資材により分包包装し、40℃/75%RH中に6ケ月間保存し、L−カルボシステインの残存率をもとめた。その結果を表3に示す。いずれの参考例も安定であった。
(Test Example 2)
About 1.5 g of the dry syrup preparation according to the present invention obtained in Reference Examples 3, 4, 5, 6 and 9, respectively, was packaged and packaged with a packaging material made of polyethylene terephthalate and aluminum, and placed in 40 ° C./75% RH. It was stored for 6 months and the residual rate of L-carbocysteine was determined. The results are shown in Table 3. All the reference examples were stable.
本発明は、L−カルボシステインの酸味を軽減したL−カルボシステインのドライシロップ剤を提供することによって、そのままでも服用し易く、用時水に懸濁あるいは溶解しても服用可能で、なおかつ小児から高齢者まで服用することができる。また本発明のL−カルボシステインのドライシロップ剤は調剤業務が比較的容易に行え、しかも携帯するうえで便利な製剤である。 The present invention provides a dry syrup preparation of L-carbocysteine with reduced acidity of L-carbocysteine, which is easy to take as it is, can be taken even when suspended or dissolved in water at the time of use, and from children It can be taken up to the elderly. The L-carbocysteine dry syrup of the present invention is a preparation which can be easily carried out and is convenient to carry.
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JP2010013357A (en) * | 2008-07-01 | 2010-01-21 | Takada Seiyaku Kk | High content l-carbocysteine dry syrup preparation |
JP5733930B2 (en) * | 2009-09-09 | 2015-06-10 | 武田薬品工業株式会社 | Solid preparation |
JP5650427B2 (en) * | 2010-03-31 | 2015-01-07 | 杏林製薬株式会社 | Pharmaceutical jelly composition |
KR20120087723A (en) * | 2011-01-28 | 2012-08-07 | 제이더블유중외제약 주식회사 | Dry syrup composition |
ES2478692B1 (en) * | 2012-12-19 | 2015-04-29 | Itf Research Pharma S.L.U. | Liquid carbocysteine formulations with improved properties |
JP6554839B2 (en) * | 2014-04-02 | 2019-08-07 | 大正製薬株式会社 | Oral composition |
CA2948070C (en) * | 2014-05-05 | 2024-02-13 | Boehringer Ingelheim International Gmbh | Fast dissolving granulate |
WO2018079734A1 (en) * | 2016-10-28 | 2018-05-03 | 第一三共株式会社 | Medicinal composition comprising memantine or pharmaceutically acceptable salt thereof |
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DE59106133D1 (en) * | 1990-10-19 | 1995-09-07 | Spirig Ag | Solid, quick-soluble pharmaceutical preparation containing S- (carboxymethyl) -L-cysteine and / or N-acetylcysteine. |
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JP2000256192A (en) * | 1999-03-05 | 2000-09-19 | Nissho Corp | Carbocysteine preparation |
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