TWI281918B - Novel composition and method for stabilizing the same - Google Patents
Novel composition and method for stabilizing the same Download PDFInfo
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- TWI281918B TWI281918B TW089121423A TW89121423A TWI281918B TW I281918 B TWI281918 B TW I281918B TW 089121423 A TW089121423 A TW 089121423A TW 89121423 A TW89121423 A TW 89121423A TW I281918 B TWI281918 B TW I281918B
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- 239000000203 mixture Substances 0.000 title abstract description 22
- 238000000034 method Methods 0.000 title description 20
- 230000000087 stabilizing effect Effects 0.000 title description 2
- 125000005456 glyceride group Chemical group 0.000 abstract description 8
- -1 diphenyl phenyl Chemical group 0.000 description 26
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 235000011187 glycerol Nutrition 0.000 description 10
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
- 239000001301 oxygen Chemical group 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 125000002950 monocyclic group Chemical group 0.000 description 7
- 125000001931 aliphatic group Chemical group 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 235000014113 dietary fatty acids Nutrition 0.000 description 6
- 229930195729 fatty acid Natural products 0.000 description 6
- 239000000194 fatty acid Substances 0.000 description 6
- 150000004665 fatty acids Chemical class 0.000 description 6
- 125000000623 heterocyclic group Chemical group 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000011593 sulfur Chemical group 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- 239000000052 vinegar Substances 0.000 description 5
- 235000021419 vinegar Nutrition 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 230000002079 cooperative effect Effects 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 125000005023 xylyl group Chemical group 0.000 description 2
- POMDLNZWFLXYLH-UHFFFAOYSA-N 2,3,4,4a,5,6,7,7a-octahydrocyclopenta[b]pyran Chemical compound C1CCOC2CCCC21 POMDLNZWFLXYLH-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000007789 gas Chemical group 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 229910052746 lanthanum Inorganic materials 0.000 description 1
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 description 1
- SQDFHQJTAWCFIB-UHFFFAOYSA-N n-methylidenehydroxylamine Chemical compound ON=C SQDFHQJTAWCFIB-UHFFFAOYSA-N 0.000 description 1
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 description 1
- WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical compound CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
Classifications
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- 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
-
- 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
- A61P11/08—Bronchodilators
-
- 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
-
- 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
- A61P27/02—Ophthalmic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/94—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/78—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Ophthalmology & Optometry (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Pyrane Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Description
AS B8 ----- 〜___ §8 第89121423號專利申請案 、 ^-------------9月30日更正替換頁 、、申請專利範圍 A為-COOH或其鹽、酯、醚或酿胺， 及X〗為_原子， W丨為=0或R4及Rs之一為氫而另一者為羥基， W2為其中尺4及R5均為氫原子者， 之為氧原子， 為飽和或不飽和二價Cl_M脂族烴基， 1為飽和或不飽和二價C1丨4脂族烴基， I為氫原子。 3.如申請專利範圍第1項之組成物，其中該甘油醋為含6 至24個碳原子之脂肪酸之甘油酯。 如申μ專利範圍第3項之組成物，其中該甘油酯為含6 至2〇個碳原子之脂肪酸之甘油酯。 如申w專利範圍第1項之組成物，其中該甘油酯為2或 夕種C6.24脂肪酸甘油醋之混合物。 6.如申請專利範圍第i項之組成物，其中該甘油酯係與其 他油溶劑混合。 7 h.. •如申請專利範圍第6項之組成物’其中該其他油溶劍為 礦物油。 8 > ’如申請專利範圍第1項之组成物，其為適於口服投藥劑 S 〇 9’如申請專利範圍第8項之組成物，係調配成膠囊。 如申請專利範圍第1項之組成物，其為適於局部投藥劑 型。 11.如申請專利範圍第1〇項之組成物，係調配成眼滴劑。 本紙張又度適肖巾g目家標準（CNS) #格（2】G )" ""— " (更正珲）91655-B4 29 (請先閱讀背面之注意事項再填寫本頁) 經濟部智慧財產局員Η消費合作社印製 10 z ASB8C8D8 第89121423號專利申請案 102年9月30日更正替換頁 六 申請專利範圍 U·—種使式⑴所示雙環化合物安定化之方法，係包詰將該 化合物與甘油酯混合之步驟者：
Wi
其 _ A 為-CH2〇H、-COCH2OH、-C〇〇H 或其鹽、酉旨 醚或醯胺； (I) ^及&為氫原子、直鏈或分支鏈Cl_6烷基或鹵原子 V1及V 2為碳原子； W!及W2為 Λ R4 R5 /\ R4 R5 或 Ο (請先闓讀背面之注意事項再填寫本\貝) 經濟部智慧財產局員工消費合作社印製 n> 其中R4及Rs為氫原子、經基 '鹵原子直鏈或分支鏈 C!·6烷基、直鏈或分支鏈Cl 6烷氧基或羥基（直鏈或分 支鏈C^6)烷基，但I及Rs不同時為羥基或直鏈或分支 鏈Cw烷氧基； z為碳、氧、硫或氣原子； I為未取代或經齒素、烧基、羥基、氧代基、未取代 本纸張尺度適用中國國家標準（ci>ls)A4規格（210 x 297公釐） (更正蜂）91655-B4 第89121423號專利申請案 102年9月30日更正替換頁 -----ίΐ A、申請專利範圍 或經取代之苯基、蔡基、甲苯基或二〒苯基或含 .個選自氮、氧或硫之雜原子之5至14員單環至三環之 雜環基取代之飽和或不飽和二價C114脂族烴基； 反2為未取代或經_素、氧代基、經基、直鏈或分支键 Cw烷基、直鏈或分支鏈Q 6烷氧基、直鏈或分支鏈 Cl·6院酿氧基、C3.6環絲、C3.6環純基、未取代或 &取代之苯基'萘基、甲苯基或二甲苯基、未取代或經 取代之苯氧基、純基、甲苯氧基或二甲苯氧基、含1 至4個選自氮.、氧或硫之雜原子之5至14員單環至三 環之雜環基或含！至4個選自氮、氧或硫之雜原子之5 至14員單環至三環之雜環基氧基取代之飽和或不飽和 Ci-u脂族烴基；Gw環烷基；環烷氧基，·未取代或 經取代之苯基、冑基、甲笨基或二甲苯基、未取代或經 取代之苯氧基、萘氧基、甲苯氧基或二甲笨氧基、含i 至4個選自氮、氧或硫之雜原子之5至14員單環至三 環之雜環基或含1至4個選自氮、氧或硫之雜原子之5 至14員單環至三環之雜環基氧基； I為氫原子、直鏈或分支鏈Ci_6烷基、Cw環烷基、未 取代或綠取代之苯基、萘基、曱苯基或二甲笨基或含i 至4個選自氮、氧或硫之雜原子之5至14員單環至三 環之雜環基。 13.如申明專利範圍第12項之方法，其中該雙環化合物為 式⑴化合物，其中 A為-COOH或其鹽、酯、趟或酿胺， 本紙張尺度適角中國國家標準Τ^Γ4^(210_χ_297公幻 (更正版)91655-Β4 31 請 先 聞 讀 背 之 注 意 事 項 再 填 寫
I ! Ϊ tf 1 I 經濟部智慧財產局員工消費合作社印製 第89121423號專利申請案 j〇2年9月30日更正替換頁 經濟部智慧財產局員工消費合作社印製 ^ 其中該其他油溶劑為 其為適於口服投藥劑 係調配成膠囊。 其為適於局部投藥劑 係調配成眼滴劑。 B8 C8 D8 '申請專利範圍 乂1及X2為齒原子， %為=〇或〜及115之一為氫而另一者為經基， W2為其中R4及Rs均為氫原子者， 2為氧原子， h為飽和或不飽和二價Cl•丨4脂族烴基， I為飽和或不飽和二價Cl-丨*脂族烴基， I為氯原子。 14. 如申請專利範圍第12項之方法，其中該甘油醋為含6 至24個碳原子之脂肪酸之甘油醋。 15. 如申請專利範圍第14項之方法，其中該甘油醋為含6 至20個碳原子之脂肪酸之甘油醋。 16. :申請專利範圍第12項之方法，曰其中該甘油醋為二或 夕種Cs·24脂肪酸甘油醋之混合物。 17. 如申請專利範圍第12項之方法，其t該甘㈣係與其 他油溶劑混合。 18. 如肀請專利範圍第17項之方法 礦物油。 19·如申請專利範·圍第12項之方法 型。 2〇·如申請專利範圍第19項之方法 21. 如申請專利範圍第12項之方.法 型0 22. 如申請專利範圍第21項之方法 23. —種下式所示之雙環化合物， 本纸張尺「 — III 1 I I I l^f\^ ---I--—i (請先閱讀背面之注意事項再填寫本頁) __C8 第89121423號專利申請案 "---___D8__| 102年9月30日更正替換頁 申請專利範圍
，1-二氟戊基）-3-羥基-2-氧雜雙環. [4.3·〇]壬烷-8-酮-7·基]庚酸。 24.(刪除）如申請專利範圍第23項之化合物，其中雙環化 合物為式（I)化合物中Χι及χ2為卤原子者。 25·(删除）如申請專利範圍第24項之化合物，其中雙環化 合物為式（I)化合物中Χι及χ2為氟原子者。 6·如申明專利範圍第5項之組成物，其_，該甘油醋為辛 酸三甘油酯及己酸三甘油酯，或植物油之混合物。 27^申請專利範.圍第12項之方法，其中，該甘油鼠為辛 酉文二甘油酯及己酸.三甘油酯，或植物油之混合物。 Μ‘如申請專利範圍第！項之組成物，其令，該雙環化合物 為 7_[(1R，3R，.6R，7幻]_3-(11_二1 戊基）3 經基_2 氧 雜雙環[4.3.0]壬烷酮-7-基]庚酸。 ”·如申請專利範圍第12項之方法，其中，該雙環化合物 為 7-[(lR，3R，6R，7R)]-3-(l山二乳戊基)_3_羥基_2 氧 雜雙環[4.3.0]壬烷·8·酮_7·基]庚酸。 30.(刪除）如申請專利範圍第23項之化合物，其中，該雙 裝--------訂---------線^/ (請先閱讀背面之注意事項再填寫本頁) m B8 C8 D8 第89121423號專利申請案 102年9月30日更正替換頁 經濟部智慧財產局員工消費合作社印製 申請專利範圍 環化合物為 7-[(lR，3R，6R，7R)]-3-(l，l-二氟戊基）-3-經基_2_氧雜雙環[4.3.0]壬烷-8-酮-7-基]庚酸》 31.如申請專利範圍第1項之組成物，其中，該雙環化合物 為 7-[(lR，6R, 7R)-3-(3S)-l，l-二氟-3-曱基戊基]-3-羥基 -2-氧雜雙環[4.3.0]壬烷-8-酮-7-基]庚酸。 32·如申請專利範圍第12項之方法，其中，該雙環化合物 為 7-[UR，6R, 7R)-3-(3S)-l，l·二氟-3-曱基戊基]-3-羥基 -2-氧雜雙環[4.3,〇]壬烷酮_7_基]庚酸。 33. (删除）如申請專利範圍第23項之化合物，其中，該雙 環化合物為 7-[(lR，6R，7R)-3-(3S)-l，l-二氟-3-曱基戊 基]·3-羥基氧雜雙環[4.3.0]壬烷-8-酮-7-基]庚酸。 34. 如申請專利範圍第1項之組成物，其中，該雙環化合物 對單環化合物之比例為至少1 : 1。- 35. 如申請專利範圍第1項之組成物，其中 對單環化合物之比例為至·少9〇 ·: ·· 1 〇·i… 36. 如申請專利範圍第1項之組成物，其中 對單環化合物之比例為約96 : 4。 〇 37. 如申請專利範圍第1項之組成物，其中 對單環化合物之比例實質上為i 〇〇 : < 38. 如申請專利範圍第12項之方法，其中 對單環化合物之比例為至少1 : 1。 39·如申請專利範圍第12項之方法，其中 對單環化合物之比例為至少90 : 1 〇。 該雙環化合物 該雙環化合物 該雙環化合物 該雙環化合物 該雙環化合物 (請先閱讀背面之注意事項再填寫本頁) 本紙最尺度週用中國國家標準（(^S)A4規格㈣x 297 (更正版）91655-B4 34 1281918 ASB88D8 第89121423號專利申請案 102年9月30日更正替換頁 ,.S 經濟部智慧財產局員工消費合作社印製 六、申請專利範圍 ：· 40. 如申請專利範圍第12項之方法，其中雙環化合物 對單環化合物之比例為約96 : 4。 41. 如申請專利範圍第12項之方法.，其中，該雙環化合物 對單環化合物之比例實質上為1〇〇: 0。 本纸張尺度適用宁國國家標準（CNS)A4規格（210 X 297公釐） (更正版）91655-B4 35 ^、裝--------訂---------線r'V.** {請先Ktff面之注意事項再填寫本一貝)
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| EP0455448B1 (en) | 1990-05-01 | 1998-12-09 | R-Tech Ueno Ltd. | Treatment of pancreatic disease with 15-keto-prostaglandin E compounds |
| JPH0446122A (ja) | 1990-06-13 | 1992-02-17 | Nippon Iyakuhin Kogyo Kk | 活性型ビタミンｄ↓３類含有製剤 |
| CA2046069C (en) | 1990-07-10 | 2002-04-09 | Ryuji Ueno | Treatment of inflammatory diseases with 15-keto-prostaglandin compounds |
| JP2938579B2 (ja) | 1990-12-15 | 1999-08-23 | 株式会社上野製薬応用研究所 | 消化管壁保護剤 |
| US5274130A (en) * | 1991-09-03 | 1993-12-28 | R-Tech Ueno Ltd. | Process for production of prostaglandin intermediates |
| JP2746800B2 (ja) * | 1991-09-03 | 1998-05-06 | 株式会社アールテック・ウエノ | プロスタグランジン中間体の製法 |
| US5474979A (en) | 1994-05-17 | 1995-12-12 | Allergan, Inc. | Nonirritating emulsions for sensitive tissue |
| CA2150287C (en) | 1994-06-03 | 2004-08-10 | Ryuji Ueno | Agent for treating hepato-biliary diseases |
| US5981607A (en) | 1998-01-20 | 1999-11-09 | Allergan | Emulsion eye drop for alleviation of dry eye related symptoms in dry eye patients and/or contact lens wearers |
| ES2221859T3 (es) * | 1999-10-15 | 2005-01-16 | Sucampo Ag | Composicion de compuestos biciclicos y procedimiento para su estabilizacion. |
| US6414016B1 (en) | 2000-09-05 | 2002-07-02 | Sucampo, A.G. | Anti-constipation composition |
| JP4210631B2 (ja) | 2004-06-24 | 2009-01-21 | 株式会社日立製作所 | ブレーキ制御装置 |
-
2000
- 2000-10-13 ES ES00966462T patent/ES2221859T3/es not_active Expired - Lifetime
- 2000-10-13 AT AT00966462T patent/ATE267189T1/de active
- 2000-10-13 ES ES04005836.4T patent/ES2309410T5/es not_active Expired - Lifetime
- 2000-10-13 TW TW089121423A patent/TWI281918B/zh not_active IP Right Cessation
- 2000-10-13 BR BRPI0014869A patent/BRPI0014869B8/pt not_active IP Right Cessation
- 2000-10-13 IL IL14880300A patent/IL148803A0/xx active IP Right Grant
- 2000-10-13 DE DE60039727T patent/DE60039727D1/de not_active Expired - Lifetime
- 2000-10-13 DK DK00966462T patent/DK1220849T3/da active
- 2000-10-13 PT PT00966462T patent/PT1220849E/pt unknown
- 2000-10-13 AR ARP000105407A patent/AR026046A1/es not_active Application Discontinuation
- 2000-10-13 HU HU1300369A patent/HU230484B1/hu not_active IP Right Cessation
- 2000-10-13 CA CA002385732A patent/CA2385732C/en not_active Expired - Lifetime
- 2000-10-13 CN CNB008143137A patent/CN1268623C/zh not_active Ceased
- 2000-10-13 TR TR2002/01032T patent/TR200201032T2/xx unknown
- 2000-10-13 DK DK04005836T patent/DK1426361T4/en active
- 2000-10-13 PT PT04005836T patent/PT1426361E/pt unknown
- 2000-10-13 CZ CZ20021037A patent/CZ303625B6/cs not_active IP Right Cessation
- 2000-10-13 HU HU0203746A patent/HU229547B1/hu not_active IP Right Cessation
- 2000-10-13 DE DE60010913T patent/DE60010913T2/de not_active Expired - Lifetime
- 2000-10-13 KR KR1020027004709A patent/KR100830061B1/ko active Protection Beyond IP Right Term
- 2000-10-13 JP JP2001530318A patent/JP4332316B2/ja not_active Expired - Lifetime
- 2000-10-13 AU AU76856/00A patent/AU780342B2/en not_active Expired
- 2000-10-13 RU RU2002112984A patent/RU2695274C3/ru active Protection Beyond IP Right Term
- 2000-10-13 EP EP04005836.4A patent/EP1426361B2/en not_active Expired - Lifetime
- 2000-10-13 MX MXPA02003756A patent/MXPA02003756A/es active IP Right Grant
- 2000-10-13 AT AT04005836T patent/ATE402925T2/de active
- 2000-10-13 EP EP00966462A patent/EP1220849B1/en not_active Expired - Lifetime
- 2000-10-13 NZ NZ518020A patent/NZ518020A/en not_active IP Right Cessation
- 2000-10-13 WO PCT/JP2000/007109 patent/WO2001027099A2/en active IP Right Grant
- 2000-10-16 US US09/688,351 patent/US6583174B1/en not_active Expired - Lifetime
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2002
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- 2002-10-07 HK HK02107337.5A patent/HK1045693B/zh not_active IP Right Cessation
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2003
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2004
- 2004-12-24 AU AU2004242503A patent/AU2004242503B2/en not_active Expired
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2008
- 2008-06-23 US US12/144,000 patent/US8088934B2/en not_active Expired - Lifetime
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2009
- 2009-05-25 JP JP2009125293A patent/JP2009235079A/ja active Pending
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2011
- 2011-11-04 US US13/289,386 patent/US8097649B1/en not_active Expired - Lifetime
- 2011-12-27 US US13/337,391 patent/US20120095090A1/en not_active Abandoned
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2013
- 2013-01-30 AR ARP130100275A patent/AR089848A2/es not_active Application Discontinuation
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2017
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