JP5628910B2 - 6−(5−クロロ−2−ピリジル)−5−[(4−メチル−1−ピペラジニル)カルボニルオキシ]−7−オキソ−6,7−ジヒドロ−5h−ピロロ[3,4−b]ピラジンの配合物 - Google Patents
6−(5−クロロ−2−ピリジル)−5−[(4−メチル−1−ピペラジニル)カルボニルオキシ]−7−オキソ−6,7−ジヒドロ−5h−ピロロ[3,4−b]ピラジンの配合物 Download PDFInfo
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- JP5628910B2 JP5628910B2 JP2012519525A JP2012519525A JP5628910B2 JP 5628910 B2 JP5628910 B2 JP 5628910B2 JP 2012519525 A JP2012519525 A JP 2012519525A JP 2012519525 A JP2012519525 A JP 2012519525A JP 5628910 B2 JP5628910 B2 JP 5628910B2
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- acid
- dosage form
- eszopiclone
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- -1 6- (5-chloro-2-pyridyl) -5-[(4-methyl-1-piperazinyl) carbonyloxy] -7-oxo-6,7-dihydro-5H-pyrrolo [3,4-B] pyrazine Compound Chemical class 0.000 title description 10
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- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 230000008454 sleep-wake cycle Effects 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007905 soft elastic gelatin capsule Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 201000001716 specific phobia Diseases 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000002600 sunflower oil Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 239000003174 triple reuptake inhibitor Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- GBBSUAFBMRNDJC-UHFFFAOYSA-N zopiclone Chemical compound C1CN(C)CCN1C(=O)OC1C2=NC=CN=C2C(=O)N1C1=CC=C(Cl)C=N1 GBBSUAFBMRNDJC-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Anesthesiology (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
(実施例1)
エスゾピクロン 3mg
フマル酸 1mg
MCC 63.3mg
A−Tab 30mg
SiO2 0.2mg
クロスカルメロース 2mg
ステアリン酸マグネシウム 0.5mg
(実施例2)
エスゾピクロン 3mg
フマル酸 3mg
MCC 61.3mg
A−Tab 30mg
SiO2 0.2mg
クロスカルメロース 2mg
ステアリン酸マグネシウム 0.5mg
(実施例3)
エスゾピクロン 3mg
フマル酸 9mg
MCC 55.3mg
A−Tab 30mg
SiO2 0.2mg
クロスカルメロース 2mg
ステアリン酸マグネシウム 0.5mg
(実施例4)
エスゾピクロン 3mg
フマル酸 18mg
MCC 46.3mg
A−Tab 30mg
SiO2 0.2mg
クロスカルメロース 2mg
ステアリン酸マグネシウム 0.5mg
(実施例5)
エスゾピクロン 3mg
L−リンゴ酸 3mg
MCC 61.3mg
A−Tab 30mg
SiO2 0.2mg
クロスカルメロース 2mg
ステアリン酸マグネシウム 0.5mg
(実施例6)
エスゾピクロン 3mg
マレイン酸 9mg
MCC 55.3mg
A−Tab 30mg
SiO2 0.2mg
クロスカルメロース 2mg
ステアリン酸マグネシウム 0.5mg
(実施例7)
エスゾピクロン 3mg
MCC 64.3mg
A−Tab 30mg
SiO2 0.2mg
クロスカルメロース 2mg
ステアリン酸マグネシウム 0.5mg
《表》
錠剤を、以下のプロトコルに従って溶解性について試験した。結果を表形式及び4つの図面(図1、図2、図3及び図4)で提供する。図1は、pH1、4.5、6.8における、及び脱イオン水中の、9%のフマル酸と調合されたエスゾピクロン遊離塩基の溶解プロファイルを示す。溶解は、比較的pHに依存性であることを理解することができる。図2は、エスゾピクロン遊離塩基並びに遊離塩基と比較した3%のフマル酸、3%のL−リンゴ酸及び9%のマレイン酸と調合された遊離塩基の水中の溶解プロファイルを示す。溶解は、本発明の組成物については急速かつ完全であり、遊離塩基については緩慢かつ不完全(1時間において)であることを理解することができる。図3は、pH1における、エスゾピクロン遊離塩基及び9%のフマル酸と調合されたエスゾピクロンの溶解プロファイルを示す。pH1において、両方の組成物は、急速かつ完全に溶解する。図4は、水中における、エスゾピクロン遊離塩基並びに1%のフマル酸、3%のフマル酸、9%のフマル酸及び20%のフマル酸と調合されたエスゾピクロンの溶解プロファイルを示す。本発明の組成物は、急速かつ完全な溶解を提供し、遊離塩基は、1時間において溶解が50%未満のままである。本発明は、錠剤からの活性成分の放出速度又は溶解速度を調整するために使用することができる。例えば、急速で完全な放出が望まれる場合、経口剤形は、約1%超の固体酸、より好ましくは、約3%超の固体酸を含むことができる。
Claims (4)
- 経口投与されるエスゾピクロンの食後溶解促進用の単一経口医薬剤形であって、前記剤形が、
(a)有効量のエスゾピクロンの遊離塩基;
(b)超化学量論量の固体酸;並びに
(c)結合剤、充填剤、崩壊剤及び/又は滑剤;
からなり、
ここで、前記エスゾピクロンの遊離塩基の有効量は、0.5mg〜5mgの量であるものとし
前記超化学量論量は、酸と塩基との1:1のモル比を超過する酸の量であり、
前記固体酸は、前記剤形の2重量%〜10重量%の量で存在するものとし、
前記崩壊剤が存在する場合には、前記崩壊剤は、寒天、アルギン酸、炭酸カルシウム、微晶性セルロース、クロスカルメロースナトリウム、クロスポビドン、ポラクリリンカリウム、デンプングリコール酸ナトリウム、ジャガイモ又はタピオカデンプンから選択されるものとする、
前記経口医薬剤形。 - 前記酸が、アジピン酸、アスパラギン酸、グルコヘプトン酸、グルコン酸、グルタミン酸、乳酸、マンデル酸、リンゴ酸、マレイン酸、フマル酸、クエン酸、アスコルビン酸、リン酸、酒石酸、トルエンスルホン酸、ベンゼンスルホン酸、コハク酸、リン酸モノナトリウム及びグルクロン酸からなる群から選択される、請求項1に記載の経口医薬剤形。
- 前記酸が、リンゴ酸、マレイン酸、フマル酸、クエン酸、アスコルビン酸、リン酸及び酒石酸から選択される、請求項1に記載の経口剤形。
- 前記酸が、マレイン酸、フマル酸、L−リンゴ酸及びD−リンゴ酸から選択される、請求項1に記載の経口剤形。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/US2009/049768 WO2011005250A1 (en) | 2009-07-07 | 2009-07-07 | Formulations of 6- (5-chloro-2-pyridyl) - 5- [ (4-methyl-1-piperazinyl) carbonyloxy] - 7-0x0-6, 7- dihydro- 5h- phyrrolo [3, 4-b] pyrazine |
Publications (2)
Publication Number | Publication Date |
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JP2012532866A JP2012532866A (ja) | 2012-12-20 |
JP5628910B2 true JP5628910B2 (ja) | 2014-11-19 |
Family
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JP2012519525A Expired - Fee Related JP5628910B2 (ja) | 2009-07-07 | 2009-07-07 | 6−(5−クロロ−2−ピリジル)−5−[(4−メチル−1−ピペラジニル)カルボニルオキシ]−7−オキソ−6,7−ジヒドロ−5h−ピロロ[3,4−b]ピラジンの配合物 |
Country Status (6)
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EP (1) | EP2451444A1 (ja) |
JP (1) | JP5628910B2 (ja) |
CN (1) | CN102470108A (ja) |
AU (1) | AU2009349456B2 (ja) |
CA (1) | CA2767238A1 (ja) |
WO (1) | WO2011005250A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
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US8212036B2 (en) | 2007-12-19 | 2012-07-03 | Sunovion Pharmaceuticals Inc. | Maleate salts of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine |
US8268832B2 (en) | 2007-12-19 | 2012-09-18 | Sunovion Pharmaceuticals Inc. | Maleate salts of 6-(5-chloro-2-Pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine |
US8269005B2 (en) | 2007-12-19 | 2012-09-18 | Sunovion Pharmaceuticals Inc. | L-malate salts of 6-(5-chloro-2-Pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-Oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine |
US8198277B2 (en) | 2007-12-19 | 2012-06-12 | Sunovion Pharmaceuticals Inc. | L-malate salts of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine |
US8198278B2 (en) | 2007-12-19 | 2012-06-12 | Sunovion Pharmaceuticals Inc. | Besylate salts of 6-(5-chloro-2-pyridyl)-5-[(4-methyl-1-piperazinyl)carbonyloxy]-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine |
CN103919780B (zh) * | 2012-12-26 | 2016-12-28 | 上海中西制药有限公司 | 镇静安眠制剂、其复方制剂、制备方法及药物组合物 |
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US5705190A (en) * | 1995-12-19 | 1998-01-06 | Abbott Laboratories | Controlled release formulation for poorly soluble basic drugs |
EP1005863A1 (en) * | 1998-12-04 | 2000-06-07 | Synthelabo | Controlled-release dosage forms comprising a short acting hypnotic or a salt thereof |
EP1064937A1 (en) * | 1999-06-28 | 2001-01-03 | Sanofi-Synthelabo | Timed dual release dosage forms comprising a short acting hypnotic or a salt thereof |
CN1418631A (zh) * | 2002-12-19 | 2003-05-21 | 王登之 | 治疗失眠的佐匹克隆口腔崩解片及其制备方法 |
WO2006002836A1 (de) * | 2004-07-01 | 2006-01-12 | Losan Pharma Gmbh | Brausezusammensetzungen von einschlafmitteln |
BRPI0513909A (pt) * | 2004-07-29 | 2008-05-20 | Sanofi Aventis | comprimido farmacêutico de camada múltipla para a liberação controlada de ingredientes ativos com solubilidade altamente dependente do ph |
EP1904499A1 (en) * | 2006-06-26 | 2008-04-02 | Teva Pharmaceutical Industries Ltd | Process for the preparation of zopiclone |
-
2009
- 2009-07-07 CA CA2767238A patent/CA2767238A1/en not_active Abandoned
- 2009-07-07 CN CN2009801608454A patent/CN102470108A/zh active Pending
- 2009-07-07 WO PCT/US2009/049768 patent/WO2011005250A1/en active Application Filing
- 2009-07-07 AU AU2009349456A patent/AU2009349456B2/en not_active Ceased
- 2009-07-07 EP EP09790099A patent/EP2451444A1/en not_active Withdrawn
- 2009-07-07 JP JP2012519525A patent/JP5628910B2/ja not_active Expired - Fee Related
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JP2012532866A (ja) | 2012-12-20 |
EP2451444A1 (en) | 2012-05-16 |
AU2009349456B2 (en) | 2015-02-05 |
AU2009349456A1 (en) | 2012-02-02 |
CN102470108A (zh) | 2012-05-23 |
WO2011005250A1 (en) | 2011-01-13 |
CA2767238A1 (en) | 2011-01-13 |
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