MX2011003400A - Antagonistas de receptores de opiaceos perifericos y uso de los mismos. - Google Patents
Antagonistas de receptores de opiaceos perifericos y uso de los mismos.Info
- Publication number
- MX2011003400A MX2011003400A MX2011003400A MX2011003400A MX2011003400A MX 2011003400 A MX2011003400 A MX 2011003400A MX 2011003400 A MX2011003400 A MX 2011003400A MX 2011003400 A MX2011003400 A MX 2011003400A MX 2011003400 A MX2011003400 A MX 2011003400A
- Authority
- MX
- Mexico
- Prior art keywords
- compound
- ppm
- bromide
- amount
- methylnaltrexone
- Prior art date
Links
- 229940079358 peripheral opioid receptor antagonist Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 399
- 239000000203 mixture Substances 0.000 claims abstract description 164
- 239000012535 impurity Substances 0.000 claims abstract description 61
- 229960002921 methylnaltrexone Drugs 0.000 claims abstract description 29
- 238000000034 method Methods 0.000 claims description 74
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 claims description 64
- 239000010937 tungsten Substances 0.000 claims description 64
- 229910052721 tungsten Inorganic materials 0.000 claims description 64
- 239000007788 liquid Substances 0.000 claims description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 45
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 40
- IFGIYSGOEZJNBE-NQMNLMSRSA-N (3r,4r,4as,7ar,12bs)-3-(cyclopropylmethyl)-4a,9-dihydroxy-3-methyl-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-3-ium-7-one;bromide Chemical compound [Br-].C([N@+]1(C)[C@@H]2CC=3C4=C(C(=CC=3)O)O[C@@H]3[C@]4([C@@]2(O)CCC3=O)CC1)C1CC1 IFGIYSGOEZJNBE-NQMNLMSRSA-N 0.000 claims description 35
- 229940071643 prefilled syringe Drugs 0.000 claims description 31
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 28
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 22
- 150000001450 anions Chemical class 0.000 claims description 22
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims description 18
- 125000001931 aliphatic group Chemical group 0.000 claims description 17
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 17
- 206010010774 Constipation Diseases 0.000 claims description 16
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- 238000010254 subcutaneous injection Methods 0.000 claims description 11
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- AAEQXEDPVFIFDK-UHFFFAOYSA-N 3-(4-fluorobenzoyl)-2-(2-methylpropanoyl)-n,3-diphenyloxirane-2-carboxamide Chemical compound C=1C=CC=CC=1NC(=O)C1(C(=O)C(C)C)OC1(C=1C=CC=CC=1)C(=O)C1=CC=C(F)C=C1 AAEQXEDPVFIFDK-UHFFFAOYSA-N 0.000 claims description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 7
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 7
- OUCSEDFVYPBLLF-KAYWLYCHSA-N 5-(4-fluorophenyl)-1-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-n,4-diphenyl-2-propan-2-ylpyrrole-3-carboxamide Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@H]2OC(=O)C[C@H](O)C2)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 OUCSEDFVYPBLLF-KAYWLYCHSA-N 0.000 claims description 6
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
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- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 claims description 5
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
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- 125000003342 alkenyl group Chemical group 0.000 claims description 4
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- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 3
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- 208000030053 Opioid-Induced Constipation Diseases 0.000 claims description 3
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Classifications
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- 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
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- 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
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- A61D7/00—Devices or methods for introducing solid, liquid, or gaseous remedies or other materials into or onto the bodies of animals
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- A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
- A61J1/00—Containers specially adapted for medical or pharmaceutical purposes
- A61J1/05—Containers specially adapted for medical or pharmaceutical purposes for collecting, storing or administering blood, plasma or medical fluids ; Infusion or perfusion containers
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- A—HUMAN NECESSITIES
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- 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
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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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/06—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with a hetero atom directly attached in position 14
- C07D489/08—Oxygen atom
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/027—Liquid chromatography
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/145555—Hetero-N
Landscapes
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- Chemical & Material Sciences (AREA)
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- Emergency Medicine (AREA)
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- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
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- Anesthesiology (AREA)
- Dermatology (AREA)
- Nutrition Science (AREA)
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- Immunology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
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- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
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- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10120108P | 2008-09-30 | 2008-09-30 | |
| US22658109P | 2009-07-17 | 2009-07-17 | |
| US23742809P | 2009-08-27 | 2009-08-27 | |
| PCT/US2009/059058 WO2010039851A1 (en) | 2008-09-30 | 2009-09-30 | Peripheral opioid receptor antagonists and uses thereof |
Publications (1)
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| MX2011003400A true MX2011003400A (es) | 2011-07-28 |
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| MX2011003400A MX2011003400A (es) | 2008-09-30 | 2009-09-30 | Antagonistas de receptores de opiaceos perifericos y uso de los mismos. |
| MX2018015087A MX2018015087A (es) | 2008-09-30 | 2009-09-30 | Antagonistas de receptores de opiaceos perifericos y usos de los mismos. |
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| MX2018015087A MX2018015087A (es) | 2008-09-30 | 2009-09-30 | Antagonistas de receptores de opiaceos perifericos y usos de los mismos. |
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|---|---|
| US (7) | US8247425B2 (https=) |
| EP (4) | EP4071151A1 (https=) |
| JP (5) | JP5719773B2 (https=) |
| KR (2) | KR20140091071A (https=) |
| CN (3) | CN102307874A (https=) |
| AR (1) | AR073520A1 (https=) |
| AU (1) | AU2009298500B2 (https=) |
| BR (2) | BRPI0919539A2 (https=) |
| CA (1) | CA2676881C (https=) |
| ES (1) | ES2914884T3 (https=) |
| HK (1) | HK1199442A1 (https=) |
| IL (2) | IL211865A (https=) |
| MX (2) | MX2011003400A (https=) |
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| PL (1) | PL3608322T3 (https=) |
| PT (1) | PT3608322T (https=) |
| RU (2) | RU2011117335A (https=) |
| SG (1) | SG194393A1 (https=) |
| WO (1) | WO2010039851A1 (https=) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HRP20150037T4 (hr) | 2003-04-08 | 2022-09-02 | Progenics Pharmaceuticals, Inc. | Farmaceutske formulacije koje sadrže metilnaltrekson |
| AR057035A1 (es) | 2005-05-25 | 2007-11-14 | Progenics Pharm Inc | SíNTESIS DE (R)-N-METILNALTREXONA, COMPOSICIONES FARMACÉUTICAS Y USOS |
| AR057325A1 (es) | 2005-05-25 | 2007-11-28 | Progenics Pharm Inc | Sintesis de (s)-n-metilnaltrexona, composiciones farmaceuticas y usos |
| TWI489984B (zh) | 2006-08-04 | 2015-07-01 | Wyeth Corp | 用於非經腸道傳輸化合物之配方及其用途 |
| TW200817048A (en) * | 2006-09-08 | 2008-04-16 | Wyeth Corp | Dry powder compound formulations and uses thereof |
| CL2008000905A1 (es) | 2007-03-29 | 2008-08-22 | Progenics Pharm Inc | Compuestos derivados de morfina, antagonistas del receptor opioide periferico; metodo de preparacion; composicion farmaceutica; y uso para reducir los efectos de la actividad opioide endogena. |
| SI2565195T1 (sl) | 2007-03-29 | 2015-09-30 | Wyeth Llc | Periferalni opioidni receptorji in antagonisti in njih uporaba |
| MX2009010550A (es) | 2007-03-29 | 2009-12-14 | Progenics Pharm Inc | Formas de cristal de bromuro de (r)-n-metilnaltrexona y uso de las mismas. |
| WO2008153725A2 (en) | 2007-05-25 | 2008-12-18 | North Carolina State University | Viral nanoparticle cell-targeted delivery platform |
| EP2240489A1 (en) | 2008-02-06 | 2010-10-20 | Progenics Pharmaceuticals, Inc. | Preparation and use of (r),(r)-2,2'-bis-methylnaltrexone |
| CA2676881C (en) * | 2008-09-30 | 2017-04-25 | Wyeth | Peripheral opioid receptor antagonists and uses thereof |
| AU2016201221B2 (en) * | 2008-09-30 | 2017-08-10 | Wyeth Llc | Peripheral opioid receptor antagonists and uses thereof |
| US9082806B2 (en) | 2008-12-12 | 2015-07-14 | Stats Chippac, Ltd. | Semiconductor device and method of forming a vertical interconnect structure for 3-D FO-WLCSP |
| US9064936B2 (en) | 2008-12-12 | 2015-06-23 | Stats Chippac, Ltd. | Semiconductor device and method of forming a vertical interconnect structure for 3-D FO-WLCSP |
| UA123856C2 (uk) | 2010-03-11 | 2021-06-16 | Уайт Елелсі | Фармацевтичні композиції метилналтрексону та натрію додецилсульфату для перорального введення |
| RU2665810C2 (ru) | 2011-10-31 | 2018-09-04 | Дженентек, Инк. | Содержащие антитела составы |
| CN102525911B (zh) * | 2012-03-20 | 2013-09-18 | 南京臣功制药股份有限公司 | 一种溴甲纳曲酮注射液及其制备方法 |
| US9192570B2 (en) * | 2013-12-20 | 2015-11-24 | AntiOP, Inc. | Intranasal naloxone compositions and methods of making and using same |
| WO2016061531A1 (en) | 2014-10-17 | 2016-04-21 | Salix Pharmaceuticals, Inc. | Use of methylnaltrexone to attenuate tumor progression |
| US20190292246A1 (en) | 2016-11-03 | 2019-09-26 | Juno Therapeutics, Inc. | Combination therapy of a cell based therapy and a microglia imhibitor |
| CN111201438A (zh) | 2017-06-02 | 2020-05-26 | 朱诺治疗学股份有限公司 | 与和细胞疗法相关的毒性有关的制品和方法 |
| AU2018275894B2 (en) | 2017-06-02 | 2025-04-24 | Juno Therapeutics, Inc. | Articles of manufacture and methods for treatment using adoptive cell therapy |
| WO2019046832A1 (en) | 2017-09-01 | 2019-03-07 | Juno Therapeutics, Inc. | GENE EXPRESSION AND EVALUATION OF RISK OF DEVELOPMENT OF TOXICITY FOLLOWING CELL THERAPY |
| US11564946B2 (en) | 2017-11-01 | 2023-01-31 | Juno Therapeutics, Inc. | Methods associated with tumor burden for assessing response to a cell therapy |
| CA3085321C (en) * | 2017-12-12 | 2023-10-31 | Xalud Therapeutics, Inc. | Halogenated derivatives of morphinans and uses thereof |
| PL3886894T3 (pl) | 2018-11-30 | 2024-07-01 | Juno Therapeutics, Inc. | Metody dawkowania i leczenia nowotworów b-komórkowych w adoptywnej terapii komórkowej |
| PL3886875T3 (pl) | 2018-11-30 | 2024-09-09 | Juno Therapeutics, Inc. | Metody leczenia z wykorzystaniem adoptywnej terapii komórkowej |
| BR112022002767A2 (pt) * | 2019-08-30 | 2022-05-10 | Helsinn Healthcare Sa | Métodos de fabricação de um comprimido de cloridrato de anamorelina, comprimidos e método para melhorar um ou mais sintomas de caquexia de câncer |
| IL293393A (en) | 2019-12-06 | 2022-07-01 | Juno Therapeutics Inc | Cell therapy-related toxicity and response-related methods for the treatment of b-cell malignancies |
Family Cites Families (254)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1420015B1 (de) | 1959-10-16 | 1971-08-26 | Boehringer Sohn Ingelheim | 2'-Hydroxy-5,9-dimethyl-6,7-benzomorphane |
| GB1202148A (en) | 1968-03-06 | 1970-08-12 | Sankyo Co | Pharmaceutical compositions |
| US3854480A (en) | 1969-04-01 | 1974-12-17 | Alza Corp | Drug-delivery system |
| US3714159A (en) | 1971-03-30 | 1973-01-30 | Janssen Pharmaceutica Nv | 2,2-diaryl-4-(4'-aryl-4'-hydroxy-piper-idino)-butyramides |
| US3884916A (en) | 1971-03-30 | 1975-05-20 | Janssen Pharmaceutica Nv | 2,2-Diaryl-4-(4-aryl-4-hydroxy-piperidino)-butyramides |
| US4326074A (en) | 1972-09-22 | 1982-04-20 | William H. Rorer, Inc. | Amidinoureas |
| US4025652A (en) | 1975-03-31 | 1977-05-24 | William H. Rorer, Inc. | Amidinoureas |
| US3937801A (en) | 1973-07-10 | 1976-02-10 | American Home Products Corporation | Reducing the incidence of gastrointestinal side effects during the treatment of inflammatory conditions with antiinflammatory drugs |
| US4060635A (en) | 1975-03-31 | 1977-11-29 | William H. Rorer, Inc. | Amidinoureas for treating diarrhea |
| US4203920A (en) | 1975-03-31 | 1980-05-20 | William H. Rorer, Inc. | Amidinoureas |
| US4066654A (en) | 1975-04-16 | 1978-01-03 | G. D. Searle & Co. | 1-triarylalkyl-4-phenyl-4-piperidine carboxylic acids and derivatives |
| US4072686A (en) | 1975-04-16 | 1978-02-07 | G. D. Searle & Co. | 1-(3,3,3-Triarylalkyl)-4-phenyl-piperidinealkanols |
| US3996214A (en) | 1976-02-23 | 1976-12-07 | G. D. Searle & Co. | 5-(1,1-Diphenyl-4-(cyclic amino) but-2-trans-en-1-yl)-2-alkyl-1,3,4-oxadiazoles and intermediates thereto |
| US4013668A (en) | 1976-03-10 | 1977-03-22 | G. D. Searle & Co. | 5-(1,1-diphenyl-3-(5- or 6-hydroxy-2-azabicyclo(2.2.2)oct-2-yl)propyl)-2-alkyl-1,3,4-oxadiazoles and related compounds |
| US4012393A (en) | 1976-03-22 | 1977-03-15 | G. D. Searle & Co. | 2-[5-(CYCLIC AMINO) ETHYL-10,11-DIHYDRO-5H-dibenzo[a,d]-cyclohepten-5- yl]-5 |
| US4115400A (en) | 1976-05-27 | 1978-09-19 | Eli Lilly And Company | 1-Azoniabicyclo[3.1.0]hexanes |
| US4176188A (en) * | 1976-11-18 | 1979-11-27 | Ortho Pharmaceutical Corp. | Utero-evacuants |
| GB1593191A (en) | 1977-03-23 | 1981-07-15 | Reckitt & Colmann Prod Ltd | Derivatives of morphine |
| US4125531A (en) | 1977-04-18 | 1978-11-14 | G. D. Searle & Co. | 2-Substituted-1-azabicyclo[2.2.2]octanes |
| US4069223A (en) | 1977-05-02 | 1978-01-17 | G. D. Searle & Co. | 4-Aminomethyl-1-(3,3,3-triarylpropyl)-4-arylpiperidine and derivatives thereof |
| US4116963A (en) | 1977-05-23 | 1978-09-26 | G.D. Searle & Co. | 3,3,3-triarylalkyl-4-phenylalkyl-4-hydroxy piperidines and related compounds |
| US4194045A (en) | 1977-12-27 | 1980-03-18 | G. D. Searle & Co. | 1-(3,3-Diaryl-3-oxadiazolalkyl)-4-phenyl-4-piperidinomethanols and related compounds |
| IT1096665B (it) | 1978-06-14 | 1985-08-26 | Tecnofarmaci Spa | Composizione farmaceutica per la terapia di stati di frigidita' ed impotenza |
| US4176186A (en) | 1978-07-28 | 1979-11-27 | Boehringer Ingelheim Gmbh | Quaternary derivatives of noroxymorphone which relieve intestinal immobility |
| JPS5535031A (en) | 1978-09-04 | 1980-03-11 | Shin Etsu Chem Co Ltd | Enteric coating composition |
| US4311833A (en) | 1979-03-06 | 1982-01-19 | Daicel Chemical Industries Ltd. | Process for preparing ethylcarboxymethylcellulose |
| US4277605A (en) | 1980-03-07 | 1981-07-07 | Bristol-Myers Company | Chemical compounds |
| US4322426A (en) | 1980-04-28 | 1982-03-30 | E. I. Du Pont De Nemours And Company | 17-Substituted-6-desoxy-7,8-dihydro-6α-methylnoroxymorphone narcotic antagonists |
| US4675189A (en) | 1980-11-18 | 1987-06-23 | Syntex (U.S.A.) Inc. | Microencapsulation of water soluble active polypeptides |
| US4466968A (en) | 1980-11-24 | 1984-08-21 | Dermall, Ltd. | Method for prophylaxis or treatment of emesis and nausea |
| US4427676A (en) | 1980-12-19 | 1984-01-24 | John Wyeth & Brother Ltd. | Thiomorpholine derivatives |
| US4377568A (en) | 1981-08-12 | 1983-03-22 | Merck Sharp & Dohme (I.A.) Corp. | Preparation of aqueous alcoholic dispersions of pH sensitive polymers and plasticizing agents and a method of enteric coating dosage forms using same |
| DK150008C (da) | 1981-11-20 | 1987-05-25 | Benzon As Alfred | Fremgangsmaade til fremstilling af et farmaceutisk oralt polydepotpraeparat |
| US4870084A (en) | 1982-03-16 | 1989-09-26 | Pfizer Inc. | Bicyclic benzo fused pyran compounds used for nausea treatment and prevention |
| EP0103636B1 (en) | 1982-03-16 | 1990-09-12 | Rockefeller University | Use of opium antagonists for the manufacture of medicaments for controlling gastrointestinal dysmotility |
| US4987136A (en) | 1982-03-16 | 1991-01-22 | The Rockefeller University | Method for controlling gastrointestinal dysmotility |
| US4430327A (en) | 1982-05-18 | 1984-02-07 | Eli Lilly And Company | Method for treating pregnant females for pain and anxiety |
| US4457907A (en) | 1982-08-05 | 1984-07-03 | Clear Lake Development Group | Composition and method for protecting a therapeutic drug |
| US4533739A (en) | 1982-10-12 | 1985-08-06 | G. D. Searle & Co. | 2-[(Aminophenyl and amidophenyl)amino]-1-azacycloalkanes having antidiarrheal activity |
| US4518433A (en) | 1982-11-08 | 1985-05-21 | Fmc Corporation | Enteric coating for pharmaceutical dosage forms |
| US4452775A (en) | 1982-12-03 | 1984-06-05 | Syntex (U.S.A.) Inc. | Cholesterol matrix delivery system for sustained release of macromolecules |
| US4462839A (en) | 1983-06-16 | 1984-07-31 | Fmc Corporation | Enteric coating for pharmaceutical dosage forms |
| US4556552A (en) | 1983-09-19 | 1985-12-03 | Colorcon, Inc. | Enteric film-coating compositions |
| EP0143949B1 (en) | 1983-11-01 | 1988-10-12 | TERUMO KABUSHIKI KAISHA trading as TERUMO CORPORATION | Pharmaceutical composition containing urokinase |
| US5266574A (en) | 1984-04-09 | 1993-11-30 | Ian S. Zagon | Growth regulation and related applications of opioid antagonists |
| US4689332A (en) | 1984-04-09 | 1987-08-25 | Research Corporation | Growth regulation and related applications of opioid antagonists |
| US4666716A (en) | 1984-09-04 | 1987-05-19 | Richardson-Vicks Inc. | Antidiarrheal compositions and use thereof |
| JPS6229515A (ja) | 1985-07-30 | 1987-02-07 | Shinjiro Tsuji | 硬カプセル剤のフイルムコ−テイング方法 |
| JPH0676314B2 (ja) | 1985-09-30 | 1994-09-28 | 花王株式会社 | 坐剤基剤及び坐剤 |
| US4824853A (en) | 1985-10-11 | 1989-04-25 | Janssen Pharmaceutica N.V. | α,α-diaryl-4-aryl-4-hydroxy-1-piperidinebutanamide, N-oxides and method of treating diarrhea |
| US4806556A (en) | 1985-12-12 | 1989-02-21 | Regents Of The University Of Minnesota | Gut-selective opiates |
| US4730048A (en) | 1985-12-12 | 1988-03-08 | Regents Of The University Of Minnesota | Gut-selective opiates |
| US4719215A (en) | 1986-03-07 | 1988-01-12 | University Of Chicago | Quaternary derivatives of noroxymorphone which relieve nausea and emesis |
| US4861781A (en) | 1986-03-07 | 1989-08-29 | The University Of Chicago | Quaternary derivatives of noroxymorphone which relieve nausea and emesis |
| DE3609073C2 (de) | 1986-03-18 | 1995-08-10 | Hans J Prof Dr Rer Nat Schmitt | Meßeinrichtung zur nichtinvasiven Feststellung peripherer Abfluß- und Durchflußstörungen in menschlichen Extremitäten |
| US4990521A (en) | 1986-07-03 | 1991-02-05 | Janssen Pharmaceutica | 4-(aroylamino)piperidine-butanimide derivatives |
| US5597564A (en) | 1986-08-28 | 1997-01-28 | Enzacor Properties Limited | Method of administering a microgranular preparation to the intestinal region of animals |
| KR940000065B1 (ko) | 1986-08-28 | 1994-01-05 | 코 사이 잉 토마스 | 동물 성장 촉진제 |
| US4888346A (en) | 1986-10-07 | 1989-12-19 | Bernard Bihari | Method for the treatment of persons infected with HTLV-III (AIDS) virus |
| US4765978A (en) | 1986-12-16 | 1988-08-23 | Schering Corporation | Novel vaginal suppository |
| FR2609632B1 (fr) | 1987-01-21 | 1991-03-29 | Shelly Marc | Nouvelle application therapeutique de la 17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxymorphinon-6-one et les compositions pharmaceutiques destinees a cet usage |
| NL8700842A (https=) | 1987-04-10 | 1988-11-01 | Duphar Int Res | |
| US4891379A (en) | 1987-04-16 | 1990-01-02 | Kabushiki Kaisha Kobe Seikosho | Piperidine opioid antagonists |
| US4857833A (en) | 1987-08-27 | 1989-08-15 | Teradyne, Inc. | Diagnosis of faults on circuit board |
| CA1315689C (en) | 1987-09-03 | 1993-04-06 | Leon I. Goldberg | Quarternary derivatives of noroxymorphone which relieve nausea and emesis |
| ES2051742T3 (es) | 1987-09-10 | 1994-07-01 | Univ Chicago | Derivados cuaternarios de noroxi-morfina que mitigan las nauseas y la emesis. |
| US4912114A (en) | 1988-03-18 | 1990-03-27 | Sandoz Ltd. | Morphinan derivatives |
| EP0350221B1 (en) | 1988-06-30 | 1996-04-17 | Astra Aktiebolag | Dermorphin analogs, their methods of preparation, pharmaceutical compositions, and methods of therapeutic treatment using the same |
| JPH0653683B2 (ja) | 1988-07-14 | 1994-07-20 | ザ ロックフェラー ユニバーシティ | 慢性痛あるいは慢性咳を治療する経口用組成物 |
| EP0352361A1 (en) | 1988-07-29 | 1990-01-31 | The Rockefeller University | Method of treating patients suffering from chronic pain or chronic cough |
| US4999342A (en) | 1988-08-16 | 1991-03-12 | Ortho Pharmaceutical Corporation | Long lasting contraceptive suppository composition and methods of use |
| US4857533A (en) | 1988-12-15 | 1989-08-15 | Baker Cummins Pharmaceuticals, Inc. | Method of treatment for autoimmune diseases |
| US4863928A (en) | 1989-01-04 | 1989-09-05 | Baker Cummins Pharmaceuticals, Inc. | Method of treatment for arthritic and inflammatory diseases |
| US5102887A (en) | 1989-02-17 | 1992-04-07 | Arch Development Corporation | Method for reducing emesis and nausea induced by the administration of an emesis causing agent |
| US5116868A (en) | 1989-05-03 | 1992-05-26 | The Johns Hopkins University | Effective ophthalmic irrigation solution |
| US5133974A (en) | 1989-05-05 | 1992-07-28 | Kv Pharmaceutical Company | Extended release pharmaceutical formulations |
| US4965269A (en) | 1989-12-20 | 1990-10-23 | Ab Hassle | Therapeutically active chloro substituted benzimidazoles |
| US5236947A (en) | 1990-02-28 | 1993-08-17 | Jouveinal S.A. | Propanamines, their pharmacological properties and their application as an antidiarrheal |
| BR9106438A (pt) | 1990-05-11 | 1993-05-18 | Pfizer | Composicoes terapeuticas sinergisticas e processos |
| JPH04230625A (ja) | 1990-12-27 | 1992-08-19 | Standard Chem & Pharmaceut Corp Ltd | 噴霧乾燥したジクロフェナクナトリウムを含み腸溶性の被覆を有するマイクロカプセルからなる微分散した錠剤組成物の製造方法 |
| CA2104229C (en) | 1991-02-25 | 1997-04-15 | Conan Kornetsky | Opiate receptor antagonist modulates movement disorder |
| CA2064373C (en) | 1991-03-29 | 2005-08-23 | Buddy Eugene Cantrell | Piperidine derivatives |
| US5159081A (en) | 1991-03-29 | 1992-10-27 | Eli Lilly And Company | Intermediates of peripherally selective n-carbonyl-3,4,4-trisubstituted piperidine opioid antagonists |
| US5250542A (en) | 1991-03-29 | 1993-10-05 | Eli Lilly And Company | Peripherally selective piperidine carboxylate opioid antagonists |
| US5270328A (en) | 1991-03-29 | 1993-12-14 | Eli Lilly And Company | Peripherally selective piperidine opioid antagonists |
| US5220017A (en) | 1991-04-10 | 1993-06-15 | Merck & Co., Inc. | Cholecystokinin antagonists |
| WO1993000077A1 (en) | 1991-06-21 | 1993-01-07 | University Of Cincinnati | Orally administrable therapeutic proteins and method of making |
| US5407686A (en) | 1991-11-27 | 1995-04-18 | Sidmak Laboratories, Inc. | Sustained release composition for oral administration of active ingredient |
| US5614219A (en) | 1991-12-05 | 1997-03-25 | Alfatec-Pharma Gmbh | Oral administration form for peptide pharmaceutical substances, in particular insulin |
| US5256154A (en) | 1992-01-31 | 1993-10-26 | Sterling Winthrop, Inc. | Pre-filled plastic syringes and containers and method of terminal sterilization thereof |
| GB2272375B (en) | 1992-04-10 | 1996-02-14 | Vnii Med Polimerov | Pharmaceutical composition |
| US5686072A (en) | 1992-06-17 | 1997-11-11 | Board Of Regents, The University Of Texas | Epitope-specific monoclonal antibodies and immunotoxins and uses thereof |
| US5512578A (en) | 1992-09-21 | 1996-04-30 | Albert Einstein College Of Medicine Of Yeshiva University, A Division Of Yeshiva University | Method of simultaneously enhancing analgesic potency and attenuating dependence liability caused by exogenous and endogenous opiod agonists |
| US5580876A (en) | 1992-09-21 | 1996-12-03 | Albert Einstein College Of Medicine Of Yeshiva University, A Division Of Yeshiva University | Method of simultaneously enhancing analgesic potency and attenuating dependence liability caused by morphine and other bimodally-acting opioid agonists |
| US6096756A (en) | 1992-09-21 | 2000-08-01 | Albert Einstein College Of Medicine Of Yeshiva University | Method of simultaneously enhancing analgesic potency and attenuating dependence liability caused by morphine and other bimodally-acting opioid agonists |
| USRE36547E (en) | 1992-09-21 | 2000-02-01 | Albert Einstein College Of Medicine Of Yeshiva University | Method of simultaneously enhancing analgesic potency and attenuating dependence liability caused by exogenous and endogenous opioid agonists |
| US5472943A (en) | 1992-09-21 | 1995-12-05 | Albert Einstein College Of Medicine Of Yeshiva University, | Method of simultaneously enhancing analgesic potency and attenuating dependence liability caused by morphine and other opioid agonists |
| BR9207175A (pt) | 1992-10-28 | 1995-12-12 | Genentech Inc | Composição contendo antagonista de fator de crescimento de célula endotelial vascular sequência aminoácida de anticorpo monoclonal polipeptídeo e método de tratamento de tumor em mamífero |
| ATE143803T1 (de) | 1992-12-22 | 1996-10-15 | Univ Cincinnati | Orale verabreichung von immunologischen aktiven biomolekülen und anderen therapeutischen proteinen |
| DE4303214A1 (de) | 1993-02-04 | 1994-08-11 | Wolfgang Marks | Behandlung von Erkrankungen viraler, viroidaler oder onkogener Genese durch Steroid-Saponine oder deren Aglykone |
| US5585348A (en) | 1993-02-10 | 1996-12-17 | Albert Einstein College Of Medicine Of Yeshiva University, A Division Of Yeshiva University | Use of excitatory opioid receptor antagonists to prevent growth factor-induced hyperalgesia |
| US5656290A (en) | 1993-02-26 | 1997-08-12 | The Procter & Gamble Company | Bisacodyl dosage form with multiple enteric polymer coatings for colonic delivery |
| US5391372A (en) | 1993-06-28 | 1995-02-21 | Campbell; Elizabeth | Methods of treating colic and founder in horses |
| AU686203B2 (en) | 1993-07-23 | 1998-02-05 | Toray Industries, Inc. | Morphinan derivative and medicinal use |
| GB2281205A (en) | 1993-08-24 | 1995-03-01 | Euro Celtique Sa | Oral opioid analgesic |
| SE9303744D0 (sv) | 1993-11-12 | 1993-11-12 | Astra Ab | Pharmaceutical emulsion |
| US5434171A (en) | 1993-12-08 | 1995-07-18 | Eli Lilly And Company | Preparation of 3,4,4-trisubstituted-piperidinyl-N-alkylcarboxylates and intermediates |
| US6190691B1 (en) | 1994-04-12 | 2001-02-20 | Adolor Corporation | Methods for treating inflammatory conditions |
| WO1995030774A1 (en) | 1994-05-05 | 1995-11-16 | Beckman Instruments, Inc. | Oligonucleotide repeat arrays |
| IT1269826B (it) | 1994-05-24 | 1997-04-15 | Paolo Minoia | Uso di antagonisti degli oppiacei e di sali di calcio per la preparazione di medicamenti per il trattamento di forme patologiche endorfino-mediate |
| US5536507A (en) | 1994-06-24 | 1996-07-16 | Bristol-Myers Squibb Company | Colonic drug delivery system |
| US5866154A (en) | 1994-10-07 | 1999-02-02 | The Dupont Merck Pharmaceutical Company | Stabilized naloxone formulations |
| US5614222A (en) | 1994-10-25 | 1997-03-25 | Kaplan; Milton R. | Stable aqueous drug suspensions and methods for preparation thereof |
| US5965161A (en) | 1994-11-04 | 1999-10-12 | Euro-Celtique, S.A. | Extruded multi-particulates |
| US5578725A (en) | 1995-01-30 | 1996-11-26 | Regents Of The University Of Minnesota | Delta opioid receptor antagonists |
| ES2094694B1 (es) | 1995-02-01 | 1997-12-16 | Esteve Quimica Sa | Nueva formulacion farmaceuticamente estable de un compuesto de bencimidazol y su proceso de obtencion. |
| US6096763A (en) | 1995-02-23 | 2000-08-01 | Merck & Co., Inc. | α1a adrenergic receptor antagonists |
| US6025154A (en) | 1995-06-06 | 2000-02-15 | Human Genome Sciences, Inc. | Polynucleotides encoding human G-protein chemokine receptor HDGNR10 |
| US5714586A (en) | 1995-06-07 | 1998-02-03 | American Cyanamid Company | Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates |
| US5821219A (en) | 1995-08-11 | 1998-10-13 | Oregon Health Sciences University | Opioid antagonists and methods of their use |
| GB9517001D0 (en) | 1995-08-18 | 1995-10-18 | Denny William | Enediyne compounds |
| US5804595A (en) | 1995-12-05 | 1998-09-08 | Regents Of The University Of Minnesota | Kappa opioid receptor agonists |
| IL133900A (en) | 1995-12-21 | 2004-07-25 | Syngenta Participations Ag | Derivatives of benzothiazole and the process for their preparation |
| ES2208870T3 (es) | 1996-02-15 | 2004-06-16 | Janssen Pharmaceutica N.V. | Uso de antagonistas del receptor 5ht4 para resolver los efectos gastrointestinales de los inhibidores de la reabsorcion de serotonina. |
| EP0914097B1 (en) | 1996-03-12 | 2002-01-16 | Alza Corporation | Composition and dosage form comprising opioid antagonist |
| US6136780A (en) | 1996-03-29 | 2000-10-24 | The Penn State Research Foundation | Control of cancer growth through the interaction of [Met5 ]-enkephalin and the zeta (ζ) receptor |
| US20040024006A1 (en) | 1996-05-06 | 2004-02-05 | Simon David Lew | Opioid pharmaceutical compositions |
| DE19651551C2 (de) * | 1996-12-11 | 2000-02-03 | Klinge Co Chem Pharm Fab | Opioidantagonisthaltige galenische Formulierung |
| US20010036469A1 (en) | 1997-01-13 | 2001-11-01 | Gooberman Lance L. | Opiate antagonist implant and process for preparation therefor |
| WO1998035679A1 (de) | 1997-02-14 | 1998-08-20 | Gödecke Aktiengesellschaft | Stabilisierung von naloxonhydrochlorid |
| US6884879B1 (en) | 1997-04-07 | 2005-04-26 | Genentech, Inc. | Anti-VEGF antibodies |
| GB9801231D0 (en) | 1997-06-05 | 1998-03-18 | Merck & Co Inc | A method of treating cancer |
| HU9701081D0 (en) | 1997-06-23 | 1997-08-28 | Gene Research Lab Inc N | Pharmaceutical composition of antitumoral activity |
| US6525038B1 (en) | 1997-06-24 | 2003-02-25 | Werner Kreutz | Synergistic compositions for the selective control of tumor tissue |
| US6353004B1 (en) | 1997-07-14 | 2002-03-05 | Adolor Coporation | Peripherally acting anti-pruritic opiates |
| US6096764A (en) | 1997-08-21 | 2000-08-01 | Eli Lilly And Company | Methods for inhibiting detrimental side-effects due to GnRH of GnRH agonist administration |
| US6099853A (en) | 1997-09-04 | 2000-08-08 | Protein Express | Vaginal suppository vaccine for urogenital infections |
| US5972954A (en) | 1997-11-03 | 1999-10-26 | Arch Development Corporation | Use of methylnaltrexone and related compounds |
| US20030158220A1 (en) | 1997-11-03 | 2003-08-21 | Foss Joseph F. | Use of methylnaltrexone and related compounds to treat chronic opioid use side effects |
| ATE210983T1 (de) | 1997-11-03 | 2002-01-15 | Stada Arzneimittel Ag | Stabilisiertes kombinationsarzneimittel enthaltend naloxone und ein opiatanalgetikum |
| AU2003204844B2 (en) | 1997-11-03 | 2007-06-07 | Arch Development Corporation | Use of methylnaltrexone and related compounds |
| US6274591B1 (en) | 1997-11-03 | 2001-08-14 | Joseph F. Foss | Use of methylnaltrexone and related compounds |
| US6559158B1 (en) | 1997-11-03 | 2003-05-06 | Ur Labs, Inc. | Use of methylnaltrexone and related compounds to treat chronic opioid use side affects |
| US6777534B1 (en) | 1997-12-09 | 2004-08-17 | Children's Medical Center Corporation | Peptide antagonists of vascular endothelial growth factor |
| EP1041987B1 (en) | 1997-12-22 | 2006-04-19 | Euro-Celtique S.A. | Pharmaceutical oral dosage form comprising a combination of an opioid agonist and naltrexone |
| EP0930334A1 (en) | 1998-01-16 | 1999-07-21 | Quest International B.V. | Polysaccharide conjugate capable of binding cellulose |
| GB9802251D0 (en) | 1998-02-03 | 1998-04-01 | Ciba Geigy Ag | Organic compounds |
| ES2267255T3 (es) | 1998-04-03 | 2007-03-01 | Ajinomoto Co., Inc. | Agentes antitumorales. |
| US6359111B1 (en) | 1998-05-28 | 2002-03-19 | Neorx Corporation | Opioid receptor targeting |
| HN1999000149A (es) | 1998-09-09 | 2000-01-12 | Pfizer Prod Inc | Derivados de 4,4-biarilpiperidina |
| US20010010919A1 (en) | 1998-10-13 | 2001-08-02 | David K. Grandy | Opioid antagonists and methods of their use |
| US6194382B1 (en) | 1999-03-03 | 2001-02-27 | Albert Einstein College Of Medicine Of Yeshiva University | Method and composition for treating irritable bowel syndrome using low doses of opioid receptor antagonists |
| JP4049477B2 (ja) | 1999-03-23 | 2008-02-20 | 大鵬薬品工業株式会社 | 副作用軽減剤 |
| US7129265B2 (en) | 1999-04-23 | 2006-10-31 | Mason R Preston | Synergistic effects of amlodipine and atorvastatin metabolite as a basis for combination therapy |
| US6171620B1 (en) | 1999-04-27 | 2001-01-09 | Health Research, Inc. | Method of enhancing the efficacy of anti-tumor agents |
| WO2000066125A1 (en) | 1999-04-29 | 2000-11-09 | Aventis Pharma S.A. | Method for treating cancer using camptothecin derivatives and 5-fluorouracil |
| US6833349B2 (en) | 1999-06-08 | 2004-12-21 | Regeneron Pharmaceuticals, Inc. | Methods of treating inflammatory skin diseases |
| US20020068712A1 (en) | 1999-07-23 | 2002-06-06 | Troy Stevens | Use of decreasing levels of functional transient receptor potential gene product |
| US20030105121A1 (en) | 1999-07-27 | 2003-06-05 | Bernard Bihari | Method of preventing lipodystrophy syndrome or reversing a pre-existing syndrome in HIV-infected patients being treated with antiretroviral agents |
| AU6934400A (en) | 1999-08-25 | 2001-03-19 | Barrett R. Cooper | Compositions and methods for treating opiate intolerance |
| AU781058B2 (en) | 1999-08-31 | 2005-05-05 | Grunenthal Gmbh | Delayed-action form of administration containing tramadol saccharinate |
| US6451806B2 (en) | 1999-09-29 | 2002-09-17 | Adolor Corporation | Methods and compositions involving opioids and antagonists thereof |
| AU776567B2 (en) | 1999-11-01 | 2004-09-16 | Evans, Brian K | Composition for treatment of constipation and irritable bowel syndrome |
| ATE306281T1 (de) | 1999-11-04 | 2005-10-15 | Roussy Inst Gustave | Antivirales mittel in kombination mit strahlentherapie zur verwendung in der behandlung von krebs |
| NZ518562A (en) | 1999-11-29 | 2005-04-29 | Adolor Corp | Novel methods and compositions involving opioids and antagonists thereof |
| US6469030B2 (en) | 1999-11-29 | 2002-10-22 | Adolor Corporation | Methods for the treatment and prevention of ileus |
| US6384044B1 (en) | 1999-11-29 | 2002-05-07 | Bernard Bihari | Method of treating cancer of the prostate |
| WO2001041705A2 (en) | 1999-11-29 | 2001-06-14 | Adolor Corporation | Novel methods for the treatment and prevention of dizziness and pruritus |
| NZ518684A (en) | 1999-11-29 | 2003-11-28 | Adolor Corp | Use of a peripheral mu opioid antagonist to treat or prevent ileus |
| US6545010B2 (en) | 2000-03-17 | 2003-04-08 | Aventis Pharma S.A. | Composition comprising camptothecin or a camptothecin derivative and a platin derivative for the treatment of cancer |
| US20010046968A1 (en) | 2000-03-23 | 2001-11-29 | Zagon Ian S. | Opioid growth factor modulates angiogenesis |
| US6967075B2 (en) | 2000-04-07 | 2005-11-22 | Schering Corporation | HCV replicase complexes |
| EP1284736A2 (en) | 2000-05-05 | 2003-02-26 | Pain Therapeutics, Inc. | Opioid antagonist compositions and dosage forms |
| AU2001270134B2 (en) | 2000-06-22 | 2006-06-15 | University Of Iowa Research Foundation | Methods for enhancing antibody-induced cell lysis and treating cancer |
| EP1175905A1 (en) | 2000-07-24 | 2002-01-30 | Societe Des Produits Nestle S.A. | Nutritional Composition |
| FI116089B (sv) | 2000-07-27 | 2005-09-15 | Johan Tore Karlstroem | Anordning och förfaranden vid reglar |
| NZ523684A (en) | 2000-07-28 | 2005-04-29 | F | New pharmaceutical composition |
| JP4183371B2 (ja) | 2000-08-31 | 2008-11-19 | 日本・バイオ株式会社 | 発酵ウコンの製造法 |
| NZ507152A (en) | 2000-09-27 | 2001-06-29 | Hiltive Pty Ltd | Wall cladding assembly with cladding having recesses along opposite sides to engage with flanges of support members |
| AU2002249885A1 (en) | 2000-11-17 | 2002-08-12 | Adolor Corporation | Delta agonist analgesics |
| CN1322143C (zh) | 2000-12-04 | 2007-06-20 | 普里马根公司 | 检测线粒体核酸与核基因核酸比率确定药物活性和/或副作用的方法 |
| US7259233B2 (en) | 2000-12-13 | 2007-08-21 | Eli Lilly And Company | Chronic treatment regimen using glucagon-like insulinotropic peptides |
| US6693125B2 (en) | 2001-01-24 | 2004-02-17 | Combinatorx Incorporated | Combinations of drugs (e.g., a benzimidazole and pentamidine) for the treatment of neoplastic disorders |
| ATE450265T1 (de) | 2001-03-23 | 2009-12-15 | Shire Canada Inc | Pharmazeutische mischung zur behandlung von krebs,die dioxolan nukleosidanalogen enthält |
| US20040242523A1 (en) | 2003-03-06 | 2004-12-02 | Ana-Farber Cancer Institue And The Univiersity Of Chicago | Chemo-inducible cancer gene therapy |
| US20040136908A1 (en) | 2001-04-09 | 2004-07-15 | Olson William C. | Anti-cd19 immunotoxins |
| WO2002087586A1 (en) | 2001-04-26 | 2002-11-07 | Control Delivery Systems, Inc. | Sustained release drug delivery system containing codrugs |
| US20030022909A1 (en) | 2001-06-05 | 2003-01-30 | University Of Chicago | Use of methylnaltrexone to treat immune suppression |
| US8012517B2 (en) | 2001-08-31 | 2011-09-06 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Inhibition of angiogenesis and destruction of angiogenic vessels with extracts of noni juice Morinda citrifolia |
| ES2654819T3 (es) | 2001-10-18 | 2018-02-15 | Nektar Therapeutics | Conjugados poliméricos de antagonistas de opioides |
| US20030144312A1 (en) | 2001-10-30 | 2003-07-31 | Schoenhard Grant L. | Inhibitors of ABC drug transporters in multidrug resistant cancer cells |
| WO2003037365A1 (en) | 2001-11-01 | 2003-05-08 | The Johns Hopkins University | Methods and compositions for treating vascular leak using hepatocyte growth factor |
| CA2470519C (en) | 2001-12-21 | 2009-11-17 | Merck & Co., Inc. | Heteroaryl substituted pyrrole modulators of metabotropic glutamate receptor-5 |
| US20050011468A1 (en) | 2002-02-04 | 2005-01-20 | Jonathan Moss | Use of methylnaltrexone in treating gastrointestinal dysfunction in equines |
| CA2475305A1 (en) | 2002-02-04 | 2004-02-19 | Jonathan Moss | Use of methylnaltrexone in treating gastrointestinal dysfunction in equines |
| US7074825B2 (en) | 2002-03-07 | 2006-07-11 | Huanbiao Mo | Composition and method for treating cancer |
| ATE510534T1 (de) | 2002-03-14 | 2011-06-15 | Euro Celtique Sa | Naltrexonhydrochlorid-zusammensetzungen |
| US20030191147A1 (en) | 2002-04-09 | 2003-10-09 | Barry Sherman | Opioid antagonist compositions and dosage forms |
| US7355081B2 (en) | 2002-04-17 | 2008-04-08 | The University Of North Carolina At Chapel Hill | Curcumin analogues and uses thereof |
| AU2003273176A1 (en) | 2002-05-17 | 2003-12-12 | Board Of Regents, The University Of Texas System | Beta-2-glycoprotein 1 is an inhibitor of angiogenesis |
| US7012100B1 (en) | 2002-06-04 | 2006-03-14 | Avolix Pharmaceuticals, Inc. | Cell migration inhibiting compositions and methods and compositions for treating cancer |
| US6986901B2 (en) | 2002-07-15 | 2006-01-17 | Warner-Lambert Company Llc | Gastrointestinal compositions |
| US20040010997A1 (en) | 2002-07-17 | 2004-01-22 | Oren Close | Guides to align masonry walls defining apertures, and methods of use |
| US7160913B2 (en) | 2002-09-13 | 2007-01-09 | Thomas Jefferson University | Methods and kit for treating Parkinson's disease |
| US7691374B2 (en) | 2002-10-23 | 2010-04-06 | Health Research, Inc. | Method for increasing the efficacy of anti-tumor agents by anti-endoglin antibody |
| ATE444295T1 (de) | 2002-11-08 | 2009-10-15 | Mallinckrodt Inc | Verfahren zur herstellung von quaternäre n-alkyl morphinan alkaloid salzen |
| WO2004054511A2 (en) | 2002-12-13 | 2004-07-01 | The Regents Of The University Of California | Analgesic combination comprising nalbuphine |
| WO2004054569A1 (en) | 2002-12-16 | 2004-07-01 | Council Of Scientific And Industrial Research | Pharmaceutical composition containing brevifoliol for use in chemotherapeutic treatment of human beings |
| ATE406360T1 (de) | 2003-03-07 | 2008-09-15 | Lilly Co Eli | Antagonisten der opioidrezeptoren |
| MXPA05010819A (es) * | 2003-04-08 | 2006-03-30 | Progenics Pharm Inc | Uso de antagonistas de opioide perifericos, especialmente metilnaltrexona para tratar sindrome de intestino irritable. |
| HRP20150037T4 (hr) | 2003-04-08 | 2022-09-02 | Progenics Pharmaceuticals, Inc. | Farmaceutske formulacije koje sadrže metilnaltrekson |
| RU2005134364A (ru) | 2003-04-08 | 2006-06-10 | Проджиникс Фармасьютикалз, Инк. (Us) | Комбинированное лечение запора |
| EP1617832B1 (en) | 2003-04-29 | 2008-03-12 | Orexigen Therapeutics, Inc. | Compositions for affecting weight loss |
| US6992193B2 (en) | 2003-06-10 | 2006-01-31 | Adolor Corporation | Sulfonylamino phenylacetamide derivatives and methods of their use |
| PL1644021T3 (pl) | 2003-06-13 | 2013-01-31 | Ironwood Pharmaceuticals Inc | Sposoby i kompozycje do leczenia zaburzeń żołądkowo-jelitowych |
| US7494979B2 (en) | 2003-06-13 | 2009-02-24 | Ironwood Pharmaceuticals, Inc. | Method for treating congestive heart failure and other disorders |
| AU2003903387A0 (en) | 2003-07-02 | 2003-07-17 | Sirtex Medical Limited | Combination therapy for treatment of neoplasia |
| EP1682006A4 (en) | 2003-10-29 | 2011-01-26 | Physiosonics Inc | METHOD AND DEVICE FOR DETERMINING A MIDDLE LINE OF AN ULTRASONIC LIQUID FLOW |
| US6984403B2 (en) | 2003-12-04 | 2006-01-10 | Pfizer Inc. | Azithromycin dosage forms with reduced side effects |
| US8946262B2 (en) | 2003-12-04 | 2015-02-03 | Adolor Corporation | Methods of preventing and treating gastrointestinal dysfunction |
| JP4225922B2 (ja) | 2004-01-15 | 2009-02-18 | アキレス株式会社 | ポリオレフィン系樹脂発泡体シート |
| US20070082044A1 (en) | 2004-03-10 | 2007-04-12 | Trustees Of Tufts College | Synergistic effect of compositions comprising carotenoids selected from lutein, beta-carotene and lycopene |
| TW200533339A (en) | 2004-03-16 | 2005-10-16 | Bristol Myers Squibb Co | Therapeutic synergy of anti-cancer compounds |
| US6946556B1 (en) | 2004-05-21 | 2005-09-20 | Acura Pharmaceuticals, Inc. | Preparation of opioid analgesics by a one-pot process |
| US7094775B2 (en) | 2004-06-30 | 2006-08-22 | Bone Care International, Llc | Method of treating breast cancer using a combination of vitamin D analogues and other agents |
| US7388008B2 (en) | 2004-08-02 | 2008-06-17 | Ambrilia Biopharma Inc. | Lysine based compounds |
| US20060063792A1 (en) | 2004-09-17 | 2006-03-23 | Adolor Corporation | Substituted morphinans and methods of their use |
| WO2006034455A2 (en) | 2004-09-23 | 2006-03-30 | Vasgene Therapeutics, Inc. | Polipeptide compounds for inhibiting angiogenesis and tumor growth |
| CN101061073A (zh) * | 2004-09-30 | 2007-10-24 | 贝克顿·迪金森公司 | 减少或消除玻璃容器中残余物的方法以及根据该方法制成的玻璃容器 |
| AU2006206454A1 (en) | 2005-01-20 | 2006-07-27 | Progenics Pharmaceuticals, Inc. | Use of methylnaltrexone and related compounds to treat post-operative gastrointestinal dysfunction |
| US8524731B2 (en) | 2005-03-07 | 2013-09-03 | The University Of Chicago | Use of opioid antagonists to attenuate endothelial cell proliferation and migration |
| ES2714198T3 (es) | 2005-03-07 | 2019-05-27 | Univ Chicago | Uso de antagonistas opioideos para atenuar la proliferación y la migración de células endoteliales |
| AR057035A1 (es) | 2005-05-25 | 2007-11-14 | Progenics Pharm Inc | SíNTESIS DE (R)-N-METILNALTREXONA, COMPOSICIONES FARMACÉUTICAS Y USOS |
| AR057325A1 (es) | 2005-05-25 | 2007-11-28 | Progenics Pharm Inc | Sintesis de (s)-n-metilnaltrexona, composiciones farmaceuticas y usos |
| CA2610951A1 (en) | 2005-06-03 | 2006-12-14 | The University Of Chicago | Modulation of microbial pathogen-host cell interactions |
| CA2609985A1 (en) | 2005-06-03 | 2007-05-10 | The University Of Chicago | Modulation of cell barrier dysfunction |
| US20080194611A1 (en) | 2005-06-03 | 2008-08-14 | Alverdy John C | Modulation of Cell Barrier Dysfunction |
| EP1899351A1 (en) | 2005-06-09 | 2008-03-19 | Mallinckrodt, Inc. | Method for separation and purification of naltrexone by preparative chromatography |
| PE20070207A1 (es) | 2005-07-22 | 2007-03-09 | Genentech Inc | Tratamiento combinado de los tumores que expresan el her |
| JP2009506080A (ja) | 2005-08-30 | 2009-02-12 | クィーンズ ユニバーシティー アット キングストン | 超低用量のα−２−受容体アンタゴニストを用いる、オピオイド受容体アゴニストの治療作用の増強方法および／またはオピオイド受容体アゴニストに対する耐性の阻害方法もしくは逆転方法 |
| PL116330U1 (en) | 2005-10-31 | 2007-04-02 | Alza Corp | Method for the reduction of alcohol provoked rapid increase in the released dose of the orally administered opioide with prolonged liberation |
| US20070259939A1 (en) | 2006-05-04 | 2007-11-08 | Accelerated Technologies | Using naltrexone as a multi-purpose health supplement to improve the human condition and preventing multiple diseases and infirmities by stimulating immune system vitality and robustness |
| US20080069871A1 (en) | 2006-07-21 | 2008-03-20 | Vaughn Jason M | Hydrophobic abuse deterrent delivery system |
| TW200815451A (en) | 2006-08-04 | 2008-04-01 | Wyeth Corp | 6-carboxy-normorphinan derivatives, synthesis and uses thereof |
| TWI489984B (zh) | 2006-08-04 | 2015-07-01 | Wyeth Corp | 用於非經腸道傳輸化合物之配方及其用途 |
| TW200817048A (en) | 2006-09-08 | 2008-04-16 | Wyeth Corp | Dry powder compound formulations and uses thereof |
| EP2099456A2 (en) | 2006-11-22 | 2009-09-16 | Progenics Pharmaceuticals, Inc. | N-oxides of 4,5-epoxy-morphinanium analogs |
| WO2008064150A1 (en) | 2006-11-22 | 2008-05-29 | Progenics Pharmaceuticals, Inc. | Processes for synthesizing quaternary 4,5-epoxy-morphinan analogs and isolating their n-stereoisomers |
| US20080176884A1 (en) | 2006-11-22 | 2008-07-24 | Progenics Pharmaceuticals, Inc. | 7,8-Saturated-4,5-Epoxy-Morphinanium Analogs |
| CL2008000905A1 (es) | 2007-03-29 | 2008-08-22 | Progenics Pharm Inc | Compuestos derivados de morfina, antagonistas del receptor opioide periferico; metodo de preparacion; composicion farmaceutica; y uso para reducir los efectos de la actividad opioide endogena. |
| SI2565195T1 (sl) | 2007-03-29 | 2015-09-30 | Wyeth Llc | Periferalni opioidni receptorji in antagonisti in njih uporaba |
| CA2676881C (en) | 2008-09-30 | 2017-04-25 | Wyeth | Peripheral opioid receptor antagonists and uses thereof |
| JP5213763B2 (ja) | 2009-03-03 | 2013-06-19 | キヤノン株式会社 | レンズ鏡筒及びそれを有する光学機器 |
| JP6522141B2 (ja) | 2015-09-17 | 2019-05-29 | 三菱電機株式会社 | 電力変換装置 |
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