TW200406205A - New formulation for the parenteral application of crobenetine - Google Patents
New formulation for the parenteral application of crobenetine Download PDFInfo
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- TW200406205A TW200406205A TW092114284A TW92114284A TW200406205A TW 200406205 A TW200406205 A TW 200406205A TW 092114284 A TW092114284 A TW 092114284A TW 92114284 A TW92114284 A TW 92114284A TW 200406205 A TW200406205 A TW 200406205A
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- 239000000203 mixture Substances 0.000 title claims abstract description 7
- 238000009472 formulation Methods 0.000 title abstract description 5
- 229950005056 crobenetine Drugs 0.000 title abstract description 3
- ILVITZMPXQQPBD-OFAXGOBFSA-N crobenetine Chemical compound O([C@H](CN1[C@@H]2CC3=CC=CC=C3[C@@H](C2(C)C)CC1)C)CC1=CC=CC=C1 ILVITZMPXQQPBD-OFAXGOBFSA-N 0.000 title abstract 2
- 150000003839 salts Chemical class 0.000 claims abstract description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 50
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 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 claims description 12
- 229930195725 Mannitol Natural products 0.000 claims description 12
- 239000008351 acetate buffer Substances 0.000 claims description 12
- 239000000594 mannitol Substances 0.000 claims description 12
- 235000010355 mannitol Nutrition 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 239000013543 active substance Substances 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 8
- 239000007853 buffer solution Substances 0.000 claims description 5
- VCCBCXVFGHTDQN-UODBTFMRSA-N BIII-890CL Chemical compound O([C@H](CN1[C@@H]2CC3=C(O)C=CC=C3[C@](C2(C)C)(C)CC1)C)CC1=CC=CC=C1 VCCBCXVFGHTDQN-UODBTFMRSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 3
- 239000000872 buffer Substances 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 239000007951 isotonicity adjuster Substances 0.000 claims description 2
- 238000007911 parenteral administration Methods 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 4
- 208000006011 Stroke Diseases 0.000 claims 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 2
- 239000000126 substance Substances 0.000 claims 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000008215 water for injection Substances 0.000 description 7
- 235000017281 sodium acetate Nutrition 0.000 description 6
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 5
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- 239000003978 infusion fluid Substances 0.000 description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- -1 phenylfluorenyloxy Chemical group 0.000 description 2
- GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 1
- GXIWMALOYDSQMW-UHFFFAOYSA-N ClCl(=O)=O Chemical compound ClCl(=O)=O GXIWMALOYDSQMW-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 229910004373 HOAc Inorganic materials 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- BOVGRCPNONTPAM-UHFFFAOYSA-N O.O.O.C(C)(=O)OCC Chemical compound O.O.O.C(C)(=O)OCC BOVGRCPNONTPAM-UHFFFAOYSA-N 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 241001520299 Phascolarctos cinereus Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 206010043647 Thrombotic Stroke Diseases 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- AUQVPWITZQHIMD-UHFFFAOYSA-N acetic acid trihydrate Chemical compound O.O.O.C(C)(=O)O.C(C)(=O)O AUQVPWITZQHIMD-UHFFFAOYSA-N 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- YBBXAUZMYYJYGV-UHFFFAOYSA-M sodium acetic acid acetate trihydrate Chemical compound O.O.O.[Na+].CC(O)=O.CC([O-])=O YBBXAUZMYYJYGV-UHFFFAOYSA-M 0.000 description 1
- 229940125794 sodium channel blocker Drugs 0.000 description 1
- 239000003195 sodium channel blocking agent Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/08—Solutions
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- 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
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- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
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- Dermatology (AREA)
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- Biochemistry (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Emergency Medicine (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
200406205 玖、發明說明： 【發明所屬之技術領域】 本發明係關於（-)-(lR，2”S)-2-(2·’-芊氧基）·丙基幾基 -5,9,9-三甲基-6,7-苯并嗎吩烷（Bill 890)或其藥理可接受鹽 之一（特別是其氫氯酸鹽）之非經口服使用（特別是靜脈施用） 之新穎調配物，其製備及應用。 【先前技術】
名詞”Bill 890”及「活性物質」始終指下式之化合物（·）_ (1R，2”S)-2-(2”-苄氧基）-丙基-4·_羥基-5,9,9-三甲基_6,7-苯 并嗎吩垸 其係由WO 99/14199專利得知，為自由驗或藥理可接受酸之 對應酸加成鹽之形式，特別是氫氯酸鹽之形式。BIII 890之 其他名稱為克比奈淀（crobenetine) &[2R-[2,3(S*)，6]]-1，2,3,4,5,6-六氫-6，11，11-三甲基-3-[2-(苯基曱氧基）丙基]_ 2,6_甲醇-3-苯甲唑辛（benzazocin)-lO-醇。Bill 890為具神經 保護性質之鈉通道阻礙劑；其應用之主要適應症為血栓性 中風、腦傷害及疼痛。 【發明内容】 本發明之目標為提供一種活性物質Bill 890 (特別是其氫 氯酸鹽）之新穎調配物。 本發明關於一種非經口服施用醫藥組合物，其含活性物 85307 200406205 質Bill 890或其藥理可拉a 、 了接又鹽 < —(特別是其氫氯酸鹽）、及 作為賦形劑之甘霞播妒 甘路糖知。甘露糖醇之量較佳為設計成產生 等滲壓溶液。 依…、本發明〈醫藥組合物可视情況地亦含其他習知賦形 d與載d例如，包括乙酸與乙酸鈉或乙酸鈉三水合物之 乙酸/乙酸鹽緩衝液’或包括如檸檬酸與磷酸氫三鋼或鱗酸 氫一鈉一水合物之檸檬酸/磷酸鹽緩衝液。通常選擇緩衝液 成刀之量以產生特定之pH值及特定之緩衝力。使用之溶劑 通常為注射用水。 較佳為，除了等滲壓劑甘露糖醇，此醫藥組合物含乙酸/ 乙酸鹽緩衝液。0.005至〇·〇5莫耳，較佳為0.005至〇 〇2莫耳具 3.8至5之pH之乙酸/乙酸鹽緩衝液更佳，而〇〇1莫耳具4ipH 之乙酸/乙酸鹽緩衝液最佳。指定之濃度係相對乙酸與乙酸 鹽一起之總濃度；由所需之pH值得到乙酸對乙酸鹽比例。指 定之pH係在純緩衝溶液及注射或灌注用最終溶液中測量。 下表提供在指定pH值之0.005、0.01與0,05莫耳乙酸/乙酸 鹽緩衝液之正確組合物作為實例。在各情形，濃度係以毫 克/毫升表示，而且以99%乙酸（"HOAc")與乙酸鈉三水合物 (，，NaOAcn)計。 莫耳濃度 0.005 0.01 0.05 pH HOAc NaOAc HOAc NaOAc HOAc NaOAc 3.8 0.268 0.074 0.535 0.148 2.68 0.74 4.0 0.2505 0.113 0.501 0.226 2.505 1.13 4.5 0.18 0.265 0.36 0.53 1.8 2.65 5.0 0.095 0.46 0.19 0.92 0.95 4.6 85307 200406205 對於上述之指示，劑量易於控制以確保安全地維持穩定 狀態血漿含量為重要的。依照本發明之Bill 890之非經口服 调配物滿足這些需求。 【實施方式】 依照本發明之Bill 890或其生理可接受鹽之一（例如，氳 氯酸鹽）之非經口服製品之一個具體實施例含每日2毫克/體 重公斤至30毫克/體重公斤，較佳為弘丨5毫克/體重公斤範圍 (劑量 < 活性物質。在各情形，指定之量、濃度與劑量係 相對活性物質基料，而無關ΒΙΠ 89〇係以「鹼」形式卜第1頁 所示之式之化合物;)或其藥理可接受鹽之一之形式使用。 為了維持穩定狀態血漿含量，此製品較佳為經24小時或 視情況地數曰連續灌注而施用。施用體積為1〇〇至5〇〇毫升 之範圍，即，活性物質施用濃度為50毫克/5〇〇毫升=〇1毫克 /¾升（0.01%)至1500毫克/500毫升=3毫克/毫升（〇·3%)之範 圍。0.03% (g/v)至 〇·2% (g/v)之濃度較佳；〇 〇3% (g/幻至 0.07% (g/ν)之濃度特佳。 活性物質之施用量可藉由施用指定體積之上述注射或灌 注用溶液之一而控制。例如，施用25〇毫升依照實例3之溶 液相當於每日施用175毫克之Bill 890。 以下之實例意圖更詳細地描述本發明： 實例 實例1 含250意克/5〇〇索升（「0.01莫耳濃度I乙酸鹽綉衝汸PH 4)之 灌注用溶液 85307 -8- 200406205
Bill 890氫氣酸鹽 甘露糖醇 99%乙酸 乙酸鈉三水合物 注射用水加至 274毫克* 25000毫克 250.5毫克 113.0毫克 500毫升 *)相當於250毫克鹼形式之Bill 890 實例2 含250亳克/500毫升（「0.01莫耳濃詹i乙酸鹽緩衝液pH 4.5) 之灌注用溶液 Bill 890氫氣酸鹽 274毫克* 甘露糖醇 25000毫克 99%乙酸 180.0毫克 乙酸鈉三水合物 265.0毫克 注射用水加至 500毫升 *)相當於250毫克鹼形式之Bill 890 實例3 含3 50毫克/500毫升（「0.02莫耳濃度，乙酸鹽緩衝液pH 4)之 灌注用溶液
Bill 890氫氣酸鹽 甘露糖醇 99%乙酸 乙酸鈉三水合物 注射用水加至 383.6 毫克 ** 25000毫克 501.0毫克 226.0毫克 500毫升 *)相當於350¾克鹼形式之Bill 890 85307 200406205 實例4
灌注用泼滋 Bill 890氫氯酸鹽 甘露糖醇 99%乙酸 乙故納三水合物 注射用水加至 767毫克 1 1000毫克 125.25毫克 56.5毫克 250毫升 ***)相當於700毫克鹼形式之BIII 890 實例5 全·2Μ·豪克/500毫升（「0.005蔞耳澧詹|乙酸鹽绥衝浚dH 4.5) 之灌注用溶汸
Bill 890氫氯酸鹽 甘露糖醇 99%乙酸 乙酸制三水合物 注射用水加至 ' 767 毫克 *** 25000毫克 90.0毫克 132.5毫克 500毫升 ***)相當於700毫克鹼形式之ΒΙΠ 89〇 實例6 盒j_.00毫克/100毫升（「〇.〇1莫耳澧麿，乙酸鹽緩衝液PH 41^· 灌注用溶液
Bill 890氫氣酸鹽 甘露糖醇 99%乙酸 219.1 毫克 **** 5〇〇〇毫克 5〇. 1毫克 85307 -10 - 200406205 乙酸鈉三水合物 22.6毫克 注射用水加至 100毫升 ****)相當於200毫克鹼形式之Bill 890 -11 - 85307
Claims (1)
- 200406205 拾、申請專利範圍·· 1· 一種醫藥組合物，其含甘露糖醇及BIII 890或其藥理可接 受鹽之一。 2·根據申請專利範圍第1項之醫藥組合物，其中使用βΙΠ 890之氫氯酸鹽作為活性物質。 3·根據申請專利範圍第1或2項之醫藥組合物，其特徵為此 組合物另外含緩衝液。 4.根據申請專利範圍第3項之醫藥組合物，其特徵為其為乙 酸/乙酸鹽緩衝液。 5 ·根據申請專利範圍第4項之醫藥組合物，其特徵為乙酸/ 乙酸鹽緩衝液具有0 005至〇〇5間之莫耳濃度及38至5之 pH 〇 6·根據申請專利範圍第丨或2項之醫藥組合物，其係用於非 經口服施用。 7·根據申請專利範圍第丨或2項之醫藥組合物，其特徵為其 意圖用於靜脈施用。 8. 根據申請專利範圍第丨或2項之醫藥組合物，其特徵為活 性物質濃度為0.1毫克/毫升至3毫克/毫升之間。 9. 一種使用甘露糖醇製備用於治療中風之含βπι 89〇或其 藥理可接受鹽之—（特別是其氫氣酸鹽）之醫藥組合物之 應用。 10. 根據中請專利範圍第9項之應用，其特徵為此醫藥組合物 另外含緩衝液。 11. 根據申請專利範圍第10項之應用，其特徵為其為乙酸/乙 85307 200406205 酸鹽緩衝液3 12·根據申請專利範圍第丨丨項之應用，其特徵為乙酸/乙酸鹽 緩衝液具有0.005至0·05間之莫耳濃度及3.8至5之pH。 13·根據申請專利範圍第9至12項中任一項之應用，其特徵為 此醫藥組合物意圖用於靜脈施用。 14.根據申請專利範圍第9至1 2項中任一項之應用，其特徵為 活性物質濃度為0」毫克/毫升至3毫克/毫升之間。 15· —種用於治療急性中風之醫藥組合物，其包含甘露糖醇 及Bill 890或其藥理可接受鹽之一。 16· —種製備用於治療中風之非經口服施用醫藥組合物（含 Bill 890或其藥理可接受鹽之一）之方法，其特徵為使用甘 露糖醇作為等滲壓劑。 17. 根據申請專利範圍第16項之方法，其特徵為此醫藥組合 物另外含緩衝液。 18. 根據申請專利範圍第17項之方法，其特徵為緩衝液為乙 酸/乙酸鹽緩衝液。 19. 根據申請專利範圍第18項之方法，其特徵為乙酸/乙酸鹽 緩衝液具有0.005至〇.〇5間之莫耳濃度及3 8至5ipH。 85307 200406205 柒、指定代表圖： (一) 本案指定代表圖為：第（）圖。 (二) 本代表圖之元件代表符號簡單說明： 捌、本案若有化學式時，請揭示最能顯示發明特徵的化學式：85307
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10223784A DE10223784A1 (de) | 2002-05-29 | 2002-05-29 | Neue Formulierung zur parenteralen Applikation von Crobenetine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW200406205A true TW200406205A (en) | 2004-05-01 |
Family
ID=29432394
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW092114284A TW200406205A (en) | 2002-05-29 | 2003-05-27 | New formulation for the parenteral application of crobenetine |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1511487A1 (zh) |
| JP (1) | JP2005531573A (zh) |
| AR (1) | AR040135A1 (zh) |
| AU (1) | AU2003240699A1 (zh) |
| CA (1) | CA2487153A1 (zh) |
| DE (1) | DE10223784A1 (zh) |
| PE (1) | PE20040067A1 (zh) |
| TW (1) | TW200406205A (zh) |
| UY (1) | UY27824A1 (zh) |
| WO (1) | WO2003099280A1 (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10223783A1 (de) * | 2002-05-29 | 2003-12-11 | Boehringer Ingelheim Pharma | Neue Formulierung zur parenteralen Applikation eines Na-Kanal-Blockers |
-
2002
- 2002-05-29 DE DE10223784A patent/DE10223784A1/de not_active Withdrawn
-
2003
- 2003-05-23 AU AU2003240699A patent/AU2003240699A1/en not_active Abandoned
- 2003-05-23 WO PCT/EP2003/005400 patent/WO2003099280A1/de not_active Ceased
- 2003-05-23 CA CA002487153A patent/CA2487153A1/en not_active Abandoned
- 2003-05-23 EP EP03730101A patent/EP1511487A1/de not_active Withdrawn
- 2003-05-23 JP JP2004506804A patent/JP2005531573A/ja active Pending
- 2003-05-27 TW TW092114284A patent/TW200406205A/zh unknown
- 2003-05-27 PE PE2003000512A patent/PE20040067A1/es not_active Application Discontinuation
- 2003-05-27 UY UY27824A patent/UY27824A1/es not_active Application Discontinuation
- 2003-05-28 AR ARP030101864A patent/AR040135A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE10223784A1 (de) | 2003-12-11 |
| WO2003099280A1 (de) | 2003-12-04 |
| AR040135A1 (es) | 2005-03-16 |
| EP1511487A1 (de) | 2005-03-09 |
| UY27824A1 (es) | 2003-12-31 |
| PE20040067A1 (es) | 2004-03-30 |
| CA2487153A1 (en) | 2003-12-04 |
| AU2003240699A1 (en) | 2003-12-12 |
| JP2005531573A (ja) | 2005-10-20 |
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