NZ560269A - Roflumilast for the treatment of diabetes mellitus - Google Patents
Roflumilast for the treatment of diabetes mellitusInfo
- Publication number
- NZ560269A NZ560269A NZ560269A NZ56026906A NZ560269A NZ 560269 A NZ560269 A NZ 560269A NZ 560269 A NZ560269 A NZ 560269A NZ 56026906 A NZ56026906 A NZ 56026906A NZ 560269 A NZ560269 A NZ 560269A
- Authority
- NZ
- New Zealand
- Prior art keywords
- roflumilast
- oxide
- diabetes mellitus
- pharmaceutically acceptable
- acceptable salt
- Prior art date
Links
- MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical compound FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 title claims abstract description 132
- 229960002586 roflumilast Drugs 0.000 title claims abstract description 129
- 206010012601 diabetes mellitus Diseases 0.000 title description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 144
- PCGSQNPMMSALEJ-UHFFFAOYSA-N roflumilast n-oxide Chemical compound ClC1=C[N+]([O-])=CC(Cl)=C1NC(=O)C1=CC=C(OC(F)F)C(OCC2CC2)=C1 PCGSQNPMMSALEJ-UHFFFAOYSA-N 0.000 claims abstract description 129
- 201000000083 maturity-onset diabetes of the young type 1 Diseases 0.000 claims abstract description 126
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 32
- 238000004519 manufacturing process Methods 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 11
- 229940124597 therapeutic agent Drugs 0.000 claims abstract 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 35
- 239000008103 glucose Substances 0.000 claims description 35
- 241000699670 Mus sp. Species 0.000 claims description 13
- 239000008280 blood Substances 0.000 claims description 13
- 210000004369 blood Anatomy 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 229920003091 Methocel™ Polymers 0.000 claims description 5
- 235000021316 daily nutritional intake Nutrition 0.000 claims description 3
- 230000002829 reductive effect Effects 0.000 claims description 3
- 230000000291 postprandial effect Effects 0.000 claims description 2
- 206010018473 Glycosuria Diseases 0.000 claims 1
- 238000010876 biochemical test Methods 0.000 claims 1
- 231100000673 dose–response relationship Toxicity 0.000 claims 1
- 230000035780 glucosuria Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 135
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 72
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 65
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 57
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 38
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 37
- 102000004877 Insulin Human genes 0.000 description 29
- 108090001061 Insulin Proteins 0.000 description 29
- 229960005095 pioglitazone Drugs 0.000 description 28
- 229940125396 insulin Drugs 0.000 description 27
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 27
- 239000003795 chemical substances by application Substances 0.000 description 25
- 229960003105 metformin Drugs 0.000 description 25
- 229960004346 glimepiride Drugs 0.000 description 21
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 21
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 20
- 239000000203 mixture Substances 0.000 description 19
- 229960004586 rosiglitazone Drugs 0.000 description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- 238000009472 formulation Methods 0.000 description 15
- 239000003112 inhibitor Substances 0.000 description 15
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 15
- -1 sulphonyl ureas Chemical class 0.000 description 15
- 239000003981 vehicle Substances 0.000 description 15
- 201000001421 hyperglycemia Diseases 0.000 description 14
- 239000002050 international nonproprietary name Substances 0.000 description 14
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 13
- 229960003365 mitiglinide Drugs 0.000 description 13
- WPGGHFDDFPHPOB-BBWFWOEESA-N mitiglinide Chemical compound C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)O)C1=CC=CC=C1 WPGGHFDDFPHPOB-BBWFWOEESA-N 0.000 description 13
- 229960003310 sildenafil Drugs 0.000 description 13
- GPCJDSXBRMKASP-UHFFFAOYSA-N 2,2-dichloro-12-(4-chlorophenyl)dodecanoic acid Chemical compound OC(=O)C(Cl)(Cl)CCCCCCCCCCC1=CC=C(Cl)C=C1 GPCJDSXBRMKASP-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 229960004329 metformin hydrochloride Drugs 0.000 description 12
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 12
- 238000011160 research Methods 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 239000003826 tablet Substances 0.000 description 12
- 229960003468 gliquidone Drugs 0.000 description 11
- RUBKYBIDEVUTQU-UHFFFAOYSA-N 6-chloro-2-phenyl-3a,4-dihydroindeno[1,2-d][1,3]thiazol-8b-ol Chemical compound S1C(CC=2C3=CC=C(Cl)C=2)C3(O)N=C1C1=CC=CC=C1 RUBKYBIDEVUTQU-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 206010022489 Insulin Resistance Diseases 0.000 description 10
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 description 10
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- 239000002552 dosage form Substances 0.000 description 10
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 10
- 238000009097 single-agent therapy Methods 0.000 description 10
- LLJFMFZYVVLQKT-UHFFFAOYSA-N 1-cyclohexyl-3-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxo-2-isoquinolinyl)ethyl]phenyl]sulfonylurea Chemical compound C=1C(OC)=CC=C(C(C2=O)(C)C)C=1C(=O)N2CCC(C=C1)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 LLJFMFZYVVLQKT-UHFFFAOYSA-N 0.000 description 9
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 9
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- XMSXOLDPMGMWTH-UHFFFAOYSA-N rivoglitazone Chemical compound CN1C2=CC(OC)=CC=C2N=C1COC(C=C1)=CC=C1CC1SC(=O)NC1=O XMSXOLDPMGMWTH-UHFFFAOYSA-N 0.000 description 9
- SUFUKZSWUHZXAV-BTJKTKAUSA-N rosiglitazone maleate Chemical compound [H+].[H+].[O-]C(=O)\C=C/C([O-])=O.C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O SUFUKZSWUHZXAV-BTJKTKAUSA-N 0.000 description 9
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- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 9
- 238000010254 subcutaneous injection Methods 0.000 description 9
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- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 8
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Neurosurgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05101772 | 2005-03-08 | ||
| PCT/EP2006/060418 WO2006094933A1 (en) | 2005-03-08 | 2006-03-03 | Roflumilast for the treatment of diabetes mellitus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ560269A true NZ560269A (en) | 2010-12-24 |
Family
ID=34938922
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ560269A NZ560269A (en) | 2005-03-08 | 2006-03-03 | Roflumilast for the treatment of diabetes mellitus |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US8017633B2 (OSRAM) |
| EP (1) | EP1874308A1 (OSRAM) |
| JP (2) | JP5091106B2 (OSRAM) |
| KR (1) | KR101302838B1 (OSRAM) |
| CN (2) | CN102600144A (OSRAM) |
| AU (1) | AU2006222060B2 (OSRAM) |
| BR (1) | BRPI0609371A2 (OSRAM) |
| CA (1) | CA2599376C (OSRAM) |
| EA (1) | EA015382B1 (OSRAM) |
| IL (2) | IL185277A (OSRAM) |
| MX (1) | MX2007010560A (OSRAM) |
| NO (1) | NO20074943L (OSRAM) |
| NZ (1) | NZ560269A (OSRAM) |
| WO (1) | WO2006094933A1 (OSRAM) |
| ZA (1) | ZA200706294B (OSRAM) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1476210B1 (en) | 2002-02-11 | 2008-09-24 | Antares Pharma, Inc. | Intradermal injector |
| CN101132820B (zh) | 2005-01-24 | 2010-05-19 | 安塔雷斯制药公司 | 预充式针辅助喷射注入器 |
| CN102600144A (zh) * | 2005-03-08 | 2012-07-25 | 奈科明有限责任公司 | 治疗糖尿病的罗氟司特 |
| TW200738266A (en) * | 2005-09-29 | 2007-10-16 | Sankyo Co | Pharmaceutical agent containing insulin resistance improving agent |
| US8251947B2 (en) | 2006-05-03 | 2012-08-28 | Antares Pharma, Inc. | Two-stage reconstituting injector |
| US9144648B2 (en) | 2006-05-03 | 2015-09-29 | Antares Pharma, Inc. | Injector with adjustable dosing |
| US20100179131A1 (en) * | 2006-09-07 | 2010-07-15 | Nycomed Gmbh | Combination treatment for diabetes mellitus |
| ES2752152T3 (es) | 2008-03-10 | 2020-04-03 | Antares Pharma Inc | Dispositivo de seguridad para inyector |
| CN101548972B (zh) * | 2008-04-03 | 2012-10-17 | 万特制药(海南)有限公司 | 一种含有瑞格列奈的固体药物组合物 |
| WO2010017285A2 (en) | 2008-08-05 | 2010-02-11 | Antares Pharma, Inc. | Multiple dosage injector |
| AU2010226442A1 (en) | 2009-03-20 | 2011-10-13 | Antares Pharma, Inc. | Hazardous agent injection system |
| US9220660B2 (en) | 2011-07-15 | 2015-12-29 | Antares Pharma, Inc. | Liquid-transfer adapter beveled spike |
| US8496619B2 (en) | 2011-07-15 | 2013-07-30 | Antares Pharma, Inc. | Injection device with cammed ram assembly |
| US20130172303A1 (en) * | 2012-01-03 | 2013-07-04 | Forest Laboratories Holdings Ltd. | Roflumilast compositions for the treatment of copd |
| US9486583B2 (en) | 2012-03-06 | 2016-11-08 | Antares Pharma, Inc. | Prefilled syringe with breakaway force feature |
| EP2833944A4 (en) | 2012-04-06 | 2016-05-25 | Antares Pharma Inc | ADMINISTRATION OF TESTOSTERONE COMPOSITIONS BY NEEDLE-SUPPORTED NOZZLE INJECTION |
| US9364610B2 (en) | 2012-05-07 | 2016-06-14 | Antares Pharma, Inc. | Injection device with cammed ram assembly |
| WO2014124427A1 (en) | 2013-02-11 | 2014-08-14 | Travanty Michael | Needle assisted jet injection device having reduced trigger force |
| WO2014124860A1 (en) | 2013-02-14 | 2014-08-21 | Boehringer Ingelheim International Gmbh | Specific pde4b-inhibitors for the treatment of diabetes mellitus |
| US9707354B2 (en) | 2013-03-11 | 2017-07-18 | Antares Pharma, Inc. | Multiple dosage injector with rack and pinion dosage system |
| WO2014165136A1 (en) | 2013-03-12 | 2014-10-09 | Antares Pharma, Inc. | Constant volume prefilled syringes and kits thereof |
| EP3165224A1 (en) * | 2015-11-09 | 2017-05-10 | Albert-Ludwigs-Universität Freiburg | Use of pde4 inhibitors for the prophylaxis and/or therapy of dyslipoproteinaemia and related disorders |
| WO2017182873A2 (en) | 2016-04-19 | 2017-10-26 | Ureka Sarl | Peptide-oligourea foldamer compounds and methods of their use |
| GB202306663D0 (en) * | 2023-05-05 | 2023-06-21 | Union Therapeutics As | Combination therapy |
Family Cites Families (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3174901A (en) * | 1963-01-31 | 1965-03-23 | Jan Marcel Didier Aron Samuel | Process for the oral treatment of diabetes |
| JPS5869812A (ja) | 1981-10-22 | 1983-04-26 | Chugai Pharmaceut Co Ltd | 血糖降下剤 |
| AR240698A1 (es) * | 1985-01-19 | 1990-09-28 | Takeda Chemical Industries Ltd | Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales |
| NZ225447A (en) | 1987-07-20 | 1991-12-23 | Merck & Co Inc | Piperazinyl derivatives of purine and purine isosteres and pharmaceutical compositions |
| US5698711A (en) * | 1991-01-28 | 1997-12-16 | Rhone-Poulenc Rorer Limited | Compounds containing phenyl linked to aryl or heteroaryl by an aliphatic- or heteroatom-containing linking group |
| GB9215633D0 (en) | 1992-07-23 | 1992-09-09 | Smithkline Beecham Plc | Novel treatment |
| EP0652868B1 (en) | 1992-07-28 | 2004-11-10 | Aventis Pharma Limited | INHIBITORS OF c-AMP PHOSPHODIESTERASE |
| JPH08509203A (ja) * | 1992-10-15 | 1996-10-01 | ダナ−ファーバー キャンサー インステテュート インコーポレイテッド | ＴＮＦ−α作用の拮抗剤を用いる肥満関連糖尿病▲ＩＩ▼型のインスリン耐性の治療 |
| SI0706513T1 (en) * | 1993-07-02 | 2002-10-31 | Altana Pharma Ag | Fluoroalkoxy-substituted benzamides and their use as cyclic nucleotide phosphodiesterase inhibitors |
| AU3265695A (en) * | 1994-08-29 | 1996-03-22 | Yamanouchi Pharmaceutical Co., Ltd. | Novel naphthyridine derivative and medicinal composition thereof |
| EA001205B1 (ru) | 1996-01-31 | 2000-12-25 | Бык Гульден Ломберг Хемише Фабрик Гмбх | Новые фенантридины |
| DE19617864A1 (de) * | 1996-04-23 | 1997-10-30 | Schering Ag | Neue chirale Phenyldihydrofuranone |
| US6331543B1 (en) * | 1996-11-01 | 2001-12-18 | Nitromed, Inc. | Nitrosated and nitrosylated phosphodiesterase inhibitors, compositions and methods of use |
| ES2222613T3 (es) | 1997-09-12 | 2005-02-01 | Pharis Biotec Gmbh | Composicion para la terapia de diabetes mellitus y de la obesidad. |
| SE9801992D0 (sv) * | 1998-06-04 | 1998-06-04 | Astra Ab | New 3-aryl-2-hydroxypropionic acid derivative I |
| ATE294793T1 (de) | 1999-01-15 | 2005-05-15 | Altana Pharma Ag | Phenantrhridin-n-oxides mit pde-iv hemmender wirkung |
| BR0007527B1 (pt) | 1999-01-15 | 2011-12-27 | fenilfenantridinas com atividade inibitària de pde-iv, seu uso, bem como medicamento compreendendo as mesmas. | |
| US7323496B2 (en) * | 1999-11-08 | 2008-01-29 | Theracos, Inc. | Compounds for treatment of inflammation, diabetes and related disorders |
| AU3270301A (en) | 1999-11-13 | 2001-05-30 | Icos Corporation | Combined pde3 and pde4 inhibitor therapy for the treatment of obesity |
| WO2001042244A1 (en) | 1999-12-08 | 2001-06-14 | Grelan Pharmaceutical Co., Ltd. | Novel 1,8-naphthyridin-2(1h)-one derivatives |
| AU2001250820A1 (en) * | 2000-03-13 | 2001-09-24 | Ortho-Mcneil Pharmaceutical, Inc. | Novel cyclohexene derivatives useful as antagonists of the motilin receptor |
| US6924292B2 (en) * | 2000-03-23 | 2005-08-02 | Takeda Chemical Industries, Ltd. | Furoisoquinoline derivatives, process for producing the same and use thereof |
| JP2003534328A (ja) * | 2000-05-25 | 2003-11-18 | メルク フロスト カナダ アンド カンパニー | フルオロアルコキシ置換ベンズアミドジクロロピリジニルｎ−オキシドｐｄｅ４阻害剤 |
| HUP0303673A3 (en) * | 2000-08-11 | 2010-04-28 | Ono Pharmaceutical Co | Piperidine derivatives and pharmaceutical compositions containing these derivatives as the active ingredient |
| KR20030023747A (ko) | 2000-08-11 | 2003-03-19 | 화이자 인코포레이티드 | 인슐린 저항성 증후군의 치료 |
| PL373301A1 (en) | 2001-01-22 | 2005-08-22 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
| OA12542A (en) * | 2001-01-31 | 2006-06-05 | Pfizer Prod Inc | Thiazolyl-, oxazolyl-, pyrrolyl-, and imidazolyl-acid amide derivatives useful as inhibitors of PDE4isozymes. |
| ES2248231T3 (es) * | 2001-01-31 | 2006-03-16 | Pfizer Products Inc. | Derivados de eteres utiles como inhibidores de las isozimas pde4. |
| HRP20030636B1 (en) | 2001-02-15 | 2012-05-31 | Nycomed Gmbh | Phthalayinone-piperidino-derivatives as pde4 inhibitors |
| EP1370211A4 (en) * | 2001-03-02 | 2005-02-09 | Bristol Myers Squibb Co | SIMULTANEOUS ADMINISTRATION OF MELANOCORTIN RECEPTOR AGONISTS AND A PHOSPHODIESTERASE HEMMER FOR THE TREATMENT OF DISEASES RELATED TO CYCLIC AMP |
| UA74912C2 (en) * | 2001-07-06 | 2006-02-15 | Merck & Co Inc | Beta-aminotetrahydroimidazo-(1,2-a)-pyrazines and tetratriazolo-(4,3-a)-pyrazines as inhibitors of dipeptylpeptidase for the treatment or prevention of diabetes |
| DE10150517A1 (de) * | 2001-10-12 | 2003-04-17 | Merck Patent Gmbh | Verwendung von Phosphodiesterase IV-Inhibitoren |
| US20030181461A1 (en) | 2002-01-25 | 2003-09-25 | Lautt Wilfred Wayne | Use of phosphodiesterase antagonists to treat insulin resistance |
| DK2020243T3 (en) * | 2002-05-28 | 2018-11-19 | Astrazeneca Ab | Pharmaceutical composition which can be applied topically |
| AU2003253130A1 (en) * | 2002-08-19 | 2004-03-03 | Glenmark Pharmaceuticals Limited | Condensed heterocyclic compounds as pde-iv inhibitors for the treatment of inflammatory and allergic disorders |
| US20060083714A1 (en) * | 2003-01-27 | 2006-04-20 | Warner James M | Combination of a pde iv inhibitor and a tnf-alpha antagonist |
| WO2004098597A1 (en) | 2003-05-12 | 2004-11-18 | Altana Pharma Ag | Composition comprising roflumilast and shuil-1r ii |
| WO2004098596A1 (en) | 2003-05-12 | 2004-11-18 | Altana Pharma Ag | Composition comprising roflumilast and il-1 trap |
| WO2004098595A1 (en) | 2003-05-12 | 2004-11-18 | Altana Pharma Ag | COMPOSITION COMPRISING ROFLUMILAST AND A TNFα ANTAGONIST |
| WO2004098598A1 (en) | 2003-05-12 | 2004-11-18 | Altana Pharma Ag | COMPOSITION COMPRISING ROFLUMILAST AND A TNFα ANTAGONIST |
| EA012279B1 (ru) * | 2003-05-22 | 2009-08-28 | Никомед Гмбх | Композиция, включающая ингибитор pde4 и ингибитор pde5 |
| WO2005020926A2 (en) * | 2003-08-28 | 2005-03-10 | Pharmacia Corporation | Treatment or prevention of vascular disorders with cox-2 inhibitors in combination with cyclic amp-specific phosphodiesterase inhibitors |
| WO2005023253A1 (en) * | 2003-09-05 | 2005-03-17 | Altana Pharma Ag | Use of pde4 inhibitors for the treatment of diabetes mellitus |
| CA2542277A1 (en) | 2003-10-21 | 2005-05-12 | Pharmacia Corporation | Method for the treatment or prevention of respiratory inflammation with a cyclooxygenase-2 inhibitor in combination with a phosphodiesterase 4 inhibitor and compositions therewith |
| CA2564139A1 (en) | 2004-04-13 | 2005-12-08 | Arena Pharmaceuticals, Inc. | Modulators of human g protein-coupled receptors for the treatment of hyperglycemia and related disorders |
| CN102600144A (zh) * | 2005-03-08 | 2012-07-25 | 奈科明有限责任公司 | 治疗糖尿病的罗氟司特 |
-
2006
- 2006-03-03 CN CN2012100579547A patent/CN102600144A/zh active Pending
- 2006-03-03 CN CN2006800072465A patent/CN101137368B/zh not_active Expired - Fee Related
- 2006-03-03 CA CA2599376A patent/CA2599376C/en not_active Expired - Fee Related
- 2006-03-03 US US11/885,450 patent/US8017633B2/en not_active Expired - Fee Related
- 2006-03-03 EA EA200701845A patent/EA015382B1/ru not_active IP Right Cessation
- 2006-03-03 WO PCT/EP2006/060418 patent/WO2006094933A1/en not_active Ceased
- 2006-03-03 AU AU2006222060A patent/AU2006222060B2/en not_active Ceased
- 2006-03-03 NZ NZ560269A patent/NZ560269A/en not_active IP Right Cessation
- 2006-03-03 BR BRPI0609371-0A patent/BRPI0609371A2/pt not_active IP Right Cessation
- 2006-03-03 JP JP2008500172A patent/JP5091106B2/ja not_active Expired - Fee Related
- 2006-03-03 KR KR1020077022434A patent/KR101302838B1/ko not_active Expired - Fee Related
- 2006-03-03 EP EP06708617A patent/EP1874308A1/en not_active Withdrawn
- 2006-03-03 MX MX2007010560A patent/MX2007010560A/es not_active Application Discontinuation
-
2007
- 2007-07-27 ZA ZA200706294A patent/ZA200706294B/xx unknown
- 2007-08-14 IL IL185277A patent/IL185277A/en not_active IP Right Cessation
- 2007-10-01 NO NO20074943A patent/NO20074943L/no not_active Application Discontinuation
-
2011
- 2011-07-11 US US13/179,895 patent/US8541456B2/en not_active Expired - Fee Related
-
2012
- 2012-06-07 JP JP2012129982A patent/JP5611275B2/ja not_active Expired - Fee Related
- 2012-07-18 IL IL221006A patent/IL221006A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2006222060B2 (en) | 2011-09-01 |
| WO2006094933A1 (en) | 2006-09-14 |
| EA200701845A1 (ru) | 2008-02-28 |
| JP2008532974A (ja) | 2008-08-21 |
| US20110269750A1 (en) | 2011-11-03 |
| ZA200706294B (en) | 2008-09-25 |
| BRPI0609371A2 (pt) | 2010-03-30 |
| MX2007010560A (es) | 2008-02-21 |
| US8017633B2 (en) | 2011-09-13 |
| CN101137368B (zh) | 2012-05-16 |
| CA2599376A1 (en) | 2006-09-14 |
| HK1116077A1 (en) | 2008-12-19 |
| IL221006A0 (en) | 2012-08-30 |
| IL185277A0 (en) | 2008-02-09 |
| CN101137368A (zh) | 2008-03-05 |
| NO20074943L (no) | 2007-10-01 |
| EA015382B1 (ru) | 2011-08-30 |
| KR20070111539A (ko) | 2007-11-21 |
| US20080214625A1 (en) | 2008-09-04 |
| JP2012188448A (ja) | 2012-10-04 |
| CN102600144A (zh) | 2012-07-25 |
| US8541456B2 (en) | 2013-09-24 |
| JP5611275B2 (ja) | 2014-10-22 |
| KR101302838B1 (ko) | 2013-09-03 |
| EP1874308A1 (en) | 2008-01-09 |
| JP5091106B2 (ja) | 2012-12-05 |
| IL185277A (en) | 2013-08-29 |
| AU2006222060A1 (en) | 2006-09-14 |
| CA2599376C (en) | 2014-05-13 |
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Legal Events
| Date | Code | Title | Description |
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| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) | ||
| RENW | Renewal (renewal fees accepted) |
Free format text: PATENT RENEWED FOR 3 YEARS UNTIL 03 MAR 2016 BY CPA GLOBAL Effective date: 20130129 |
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| ASS | Change of ownership |
Owner name: TAKEDA GMBH, DE Effective date: 20150305 |
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| LAPS | Patent lapsed |