JP4827367B2 - Dry syrup - Google Patents
Dry syrup Download PDFInfo
- Publication number
- JP4827367B2 JP4827367B2 JP2002544066A JP2002544066A JP4827367B2 JP 4827367 B2 JP4827367 B2 JP 4827367B2 JP 2002544066 A JP2002544066 A JP 2002544066A JP 2002544066 A JP2002544066 A JP 2002544066A JP 4827367 B2 JP4827367 B2 JP 4827367B2
- Authority
- JP
- Japan
- Prior art keywords
- carbocysteine
- sodium
- dry syrup
- manufactured
- mixed
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 239000006188 syrup Substances 0.000 title claims description 27
- 235000020357 syrup Nutrition 0.000 title claims description 27
- GBFLZEXEOZUWRN-VKHMYHEASA-N S-carboxymethyl-L-cysteine Chemical compound OC(=O)[C@@H](N)CSCC(O)=O GBFLZEXEOZUWRN-VKHMYHEASA-N 0.000 claims description 33
- 238000002360 preparation method Methods 0.000 claims description 23
- 239000008187 granular material Substances 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 229920002472 Starch Polymers 0.000 claims description 11
- 239000011734 sodium Substances 0.000 claims description 11
- 229910052708 sodium Inorganic materials 0.000 claims description 11
- 239000008107 starch Substances 0.000 claims description 11
- 235000019698 starch Nutrition 0.000 claims description 11
- 150000005846 sugar alcohols Chemical class 0.000 claims description 9
- 239000008123 high-intensity sweetener Substances 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 235000013615 non-nutritive sweetener Nutrition 0.000 claims description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 12
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 12
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 12
- 235000009508 confectionery Nutrition 0.000 description 12
- 229920002785 Croscarmellose sodium Polymers 0.000 description 11
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 11
- 229960001681 croscarmellose sodium Drugs 0.000 description 11
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 11
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 11
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 108010011485 Aspartame Proteins 0.000 description 9
- 239000000605 aspartame Substances 0.000 description 9
- 235000010357 aspartame Nutrition 0.000 description 9
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 9
- 229960003438 aspartame Drugs 0.000 description 9
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 9
- 239000004299 sodium benzoate Substances 0.000 description 9
- 235000010234 sodium benzoate Nutrition 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 229920000881 Modified starch Polymers 0.000 description 7
- 239000000796 flavoring agent Substances 0.000 description 7
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 7
- YOBAEOGBNPPUQV-UHFFFAOYSA-N iron;trihydrate Chemical compound O.O.O.[Fe].[Fe] YOBAEOGBNPPUQV-UHFFFAOYSA-N 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000005469 granulation Methods 0.000 description 6
- 230000003179 granulation Effects 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 235000019634 flavors Nutrition 0.000 description 5
- 235000019502 Orange oil Nutrition 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000011248 coating agent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000007884 disintegrant Substances 0.000 description 4
- 239000010502 orange oil Substances 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 235000012239 silicon dioxide Nutrition 0.000 description 4
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 4
- 240000000560 Citrus x paradisi Species 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 235000016623 Fragaria vesca Nutrition 0.000 description 3
- 240000009088 Fragaria x ananassa Species 0.000 description 3
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 3
- BIVBRWYINDPWKA-VLQRKCJKSA-L Glycyrrhizinate dipotassium Chemical compound [K+].[K+].O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C([O-])=O)[C@@H]1O[C@H](C([O-])=O)[C@@H](O)[C@H](O)[C@H]1O BIVBRWYINDPWKA-VLQRKCJKSA-L 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 229940101029 dipotassium glycyrrhizinate Drugs 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000009423 ventilation Methods 0.000 description 3
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 2
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 2
- 244000144730 Amygdalus persica Species 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 235000006040 Prunus persica var persica Nutrition 0.000 description 2
- 239000004288 Sodium dehydroacetate Substances 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 2
- 235000013736 caramel Nutrition 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 229950008138 carmellose Drugs 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 229960000913 crospovidone Drugs 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- 239000004302 potassium sorbate Substances 0.000 description 2
- 235000010241 potassium sorbate Nutrition 0.000 description 2
- 229940069338 potassium sorbate Drugs 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229940079839 sodium dehydroacetate Drugs 0.000 description 2
- 235000019259 sodium dehydroacetate Nutrition 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- -1 sucrose fatty acid ester Chemical class 0.000 description 2
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 1
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010009137 Chronic sinusitis Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 1
- 235000019801 trisodium phosphate Nutrition 0.000 description 1
- 239000008371 vanilla flavor Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
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- 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 or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [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
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- Otolaryngology (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
技術分野
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。
背景技術
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。
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。
発明の開示
本発明者らは、Ｌ−カルボシステインを含んた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、そのままでも、あるいは水に懸濁または溶解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と高甘味度甘味剤を配合することで、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、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。
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。
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。
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。
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。
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。
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。
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。
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。
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。
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。
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。
発明を実施するための最良の形態
以下実施例により本発明を説明するが、本発明はこれらの実施例によって限定されるものではない。
（実施例１）
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。
（実施例２）
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。
（実施例３）
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。
（実施例４）
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。
（実施例５）
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。
（実施例６）
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。
（実施例７）
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。
（実施例８）
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。
（実施例９）
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。
（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実施例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。
実施例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。いずれの実施例も安定であった。
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。TECHNICAL FIELD The present invention relates to a dry syrup preparation 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.
Background Art L-carbocysteine normalizes the content ratio of various mucins contained in the airway mucosa and lowers the viscosity of 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.
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.
DISCLOSURE OF THE INVENTION The present inventors have reduced the acidity of L-carbocysteine through a simpler manufacturing process without applying special processing such as coating to granules containing L-carbocysteine, so that they can be taken, formulated and carried. A dry syrup preparation was completed that was convenient and could be taken as it was or suspended or dissolved in water.
That is, the present invention provides a dry syrup formulation that achieves a reduction in the acidity of L-carbocysteine by a simple manufacturing process that does not require special processing such as coating, by combining a sugar alcohol and a high-intensity sweetener. Is.
The dry syrup of L-carbocysteine thus obtained can be dispensed relatively easily, is convenient for carrying, is easy to take as it is, and can be suspended or dissolved in water at the time of use. It is a preparation that can be taken from children to the elderly.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described below with reference to examples, but the present invention is not limited to these examples.
Example 1
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.
(Example 2)
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.
(Example 3)
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.
Example 4
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.
(Example 5)
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 type, 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.
(Example 6)
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.
(Example 7)
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.
(Example 8)
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.
Example 9
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.
(Test Example 1)
The control and the preparations of Examples 1 to 9 in which L-carbocysteine, sugar alcohol and high-intensity sweetener were mixed at the following mixing ratio were examined for taste and ingestion. 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.
For the dry syrups according to the present invention obtained in Examples 3, 4, 5, 6 and 9, 1.5 g each was packaged and packaged with a packaging material consisting of polyethylene terephthalate and aluminum, and 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 examples were stable.
Claims (4)
Priority Applications (1)
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|---|---|---|---|
| JP2002544066A JP4827367B2 (en) | 2000-11-21 | 2001-11-20 | Dry syrup |
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| JP2000353839 | 2000-11-21 | ||
| JP2000353839 | 2000-11-21 | ||
| PCT/JP2001/010110 WO2002041887A1 (en) | 2000-11-21 | 2001-11-20 | Dry syrup preparations |
| JP2002544066A JP4827367B2 (en) | 2000-11-21 | 2001-11-20 | Dry syrup |
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| JP2008226643A Expired - Lifetime JP4987825B2 (en) | 2000-11-21 | 2008-09-04 | Dry syrup |
| JP2012000701A Expired - Lifetime JP5566408B2 (en) | 2000-11-21 | 2012-01-05 | Dry syrup |
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| JP2012000701A Expired - Lifetime JP5566408B2 (en) | 2000-11-21 | 2012-01-05 | Dry syrup |
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| JP4827367B2 (en) * | 2000-11-21 | 2011-11-30 | 杏林製薬株式会社 | Dry syrup |
| 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 |
| HUE042861T2 (en) * | 2014-05-05 | 2019-07-29 | Sanofi Aventis Deutschland | Fast dissolving granulate |
| TW201818928A (en) * | 2016-10-28 | 2018-06-01 | 日商第一三共股份有限公司 | Pharmaceutical composition containing memantine or pharmaceutically acceptable salt thereof |
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| JPH0696536B2 (en) * | 1988-02-26 | 1994-11-30 | 佐藤製薬株式会社 | Internal suspension containing antacid |
| DK0481294T4 (en) * | 1990-10-19 | 2001-06-18 | Spirig Ag | Solid, fast-soluble drug preparation containing N-acetylcysteine |
| JP3265680B2 (en) * | 1992-03-12 | 2002-03-11 | 大正製薬株式会社 | Oral pharmaceutical composition |
| JPH0616556A (en) * | 1992-07-02 | 1994-01-25 | Yoshitomi Pharmaceut Ind Ltd | Slightly soluble medicine-containing preparation |
| JPH06157312A (en) * | 1992-11-12 | 1994-06-03 | Shionogi & Co Ltd | Bitterness-improved dry syrup granule of terfenadine |
| JPH0717866A (en) * | 1993-06-16 | 1995-01-20 | Meiji Seika Kaisha Ltd | Medicinal composition |
| JPH0827034A (en) * | 1994-07-14 | 1996-01-30 | Nikken Chem Co Ltd | Liquid agent for internal use containing erythritol |
| EP0826376B1 (en) * | 1995-05-02 | 2007-01-24 | Taisho Pharmaceutical Co. Ltd | Composition for oral administration |
| JPH08337532A (en) * | 1995-06-14 | 1996-12-24 | Takeda Chem Ind Ltd | Medicinal composition |
| AR004014A1 (en) * | 1995-10-13 | 1998-09-30 | Meiji Seika Kaisha | AN ANTIBACTERIAL COMPOSITION OF CEFDITOREN PIVOXILO FOR ORAL ADMINISTRATION AND METHOD TO OBTAIN SUCH COMPOSITION |
| JPH09227364A (en) * | 1996-02-23 | 1997-09-02 | Grelan Pharmaceut Co Ltd | Stable teprenone formulation |
| EP1072264A4 (en) * | 1998-04-16 | 2004-07-28 | Ajinomoto Kk | Remedies for primary biliary cirrhosis |
| JP3596742B2 (en) * | 1998-07-31 | 2004-12-02 | 日研化学株式会社 | Cation exchange resin formulation |
| JP2000191519A (en) * | 1998-12-25 | 2000-07-11 | Nippon Kayaku Co Ltd | Rapid release granule wherein unpleasant functional property of medicinally active ingredient is masked |
| JP2000256192A (en) * | 1999-03-05 | 2000-09-19 | Nissho Corp | Carbocysteine preparation |
| JP2000273051A (en) * | 1999-03-19 | 2000-10-03 | Kobayashi Pharmaceut Co Ltd | Liquid preparation whose bitter taste is masked |
| JP4827367B2 (en) * | 2000-11-21 | 2011-11-30 | 杏林製薬株式会社 | Dry syrup |
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2001
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| JP2014074079A (en) | 2014-04-24 |
| JPWO2002041887A1 (en) | 2004-03-25 |
| JP2012067136A (en) | 2012-04-05 |
| JP6154758B2 (en) | 2017-06-28 |
| WO2002041887A1 (en) | 2002-05-30 |
| JP2009019054A (en) | 2009-01-29 |
| JP4987825B2 (en) | 2012-07-25 |
| JP5566408B2 (en) | 2014-08-06 |
| AU2002224053A1 (en) | 2002-06-03 |
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