DE60004181T2 - Behandlung der pulmonalen hypertension durch inhalation von benzinden-prostaglandine - Google Patents
Behandlung der pulmonalen hypertension durch inhalation von benzinden-prostaglandine Download PDFInfo
- Publication number
- DE60004181T2 DE60004181T2 DE60004181T DE60004181T DE60004181T2 DE 60004181 T2 DE60004181 T2 DE 60004181T2 DE 60004181 T DE60004181 T DE 60004181T DE 60004181 T DE60004181 T DE 60004181T DE 60004181 T2 DE60004181 T2 DE 60004181T2
- Authority
- DE
- Germany
- Prior art keywords
- baseline
- aerosolized
- pulmonary
- intravenous
- aerosol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 206010020772 Hypertension Diseases 0.000 title description 9
- PAJMKGZZBBTTOY-ZFORQUDYSA-N treprostinil Chemical compound C1=CC=C(OCC(O)=O)C2=C1C[C@@H]1[C@@H](CC[C@@H](O)CCCCC)[C@H](O)C[C@@H]1C2 PAJMKGZZBBTTOY-ZFORQUDYSA-N 0.000 claims abstract description 133
- -1 benzindene prostaglandins Chemical class 0.000 claims abstract description 32
- 208000002815 pulmonary hypertension Diseases 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 2
- 230000000144 pharmacologic effect Effects 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 150000003180 prostaglandins Chemical class 0.000 claims description 2
- KXYGKDBONOVZOM-UHFFFAOYSA-N 1h-cyclopenta[a]naphthalene Chemical class C1=CC=CC2=C3CC=CC3=CC=C21 KXYGKDBONOVZOM-UHFFFAOYSA-N 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000012730 sustained-release form Substances 0.000 claims 1
- 241001494479 Pecora Species 0.000 abstract description 26
- 229940094443 oxytocics prostaglandins Drugs 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 4
- 238000001990 intravenous administration Methods 0.000 description 57
- 230000000694 effects Effects 0.000 description 45
- DJKDIKIDYDXHDD-IGUVKOCZSA-N U-44069 Chemical compound C1O[C@@H]2[C@H](C\C=C/CCCC(O)=O)[C@@H](/C=C/[C@@H](O)CCCCC)[C@H]1C2 DJKDIKIDYDXHDD-IGUVKOCZSA-N 0.000 description 33
- 239000000243 solution Substances 0.000 description 33
- 230000036593 pulmonary vascular resistance Effects 0.000 description 32
- 239000000443 aerosol Substances 0.000 description 27
- 231100000673 dose–response relationship Toxicity 0.000 description 23
- 230000004872 arterial blood pressure Effects 0.000 description 22
- 210000002216 heart Anatomy 0.000 description 22
- 230000002685 pulmonary effect Effects 0.000 description 21
- 230000000747 cardiac effect Effects 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 16
- 238000001802 infusion Methods 0.000 description 16
- 210000001147 pulmonary artery Anatomy 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 13
- 239000000203 mixture Substances 0.000 description 11
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 10
- 230000003247 decreasing effect Effects 0.000 description 10
- 230000009885 systemic effect Effects 0.000 description 10
- 230000002792 vascular Effects 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 8
- 210000004072 lung Anatomy 0.000 description 8
- 208000004248 Familial Primary Pulmonary Hypertension Diseases 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000001746 atrial effect Effects 0.000 description 7
- 230000017531 blood circulation Effects 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000006199 nebulizer Substances 0.000 description 6
- 201000008312 primary pulmonary hypertension Diseases 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Chemical class 0.000 description 5
- 238000012387 aerosolization Methods 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000000004 hemodynamic effect Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000001509 sodium citrate Substances 0.000 description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 208000018262 Peripheral vascular disease Diseases 0.000 description 3
- 206010039163 Right ventricular failure Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 208000021267 infertility disease Diseases 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000002093 peripheral effect Effects 0.000 description 3
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 208000037812 secondary pulmonary hypertension Diseases 0.000 description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 201000006306 Cor pulmonale Diseases 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- 208000004186 Pulmonary Heart Disease Diseases 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 229960004676 antithrombotic agent Drugs 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229960004106 citric acid Drugs 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000012377 drug delivery Methods 0.000 description 2
- 229960001123 epoprostenol Drugs 0.000 description 2
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000007427 paired t-test Methods 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000004088 pulmonary circulation Effects 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000005526 vasoconstrictor agent Substances 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
- VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical compound CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
- WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
- 208000010444 Acidosis Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- XZFRIPGNUQRGPI-WLPVIMDJSA-N Carbacyclin Chemical class C1\C(=C\CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 XZFRIPGNUQRGPI-WLPVIMDJSA-N 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010021133 Hypoventilation Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010024119 Left ventricular failure Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 208000034530 PLAA-associated neurodevelopmental disease Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 208000035286 Spontaneous Remission Diseases 0.000 description 1
- 238000010161 Student-Newman-Keuls test Methods 0.000 description 1
- IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 230000007950 acidosis Effects 0.000 description 1
- 208000026545 acidosis disease Diseases 0.000 description 1
- 206010001053 acute respiratory failure Diseases 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 208000008445 altitude sickness Diseases 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 229960004543 anhydrous citric acid Drugs 0.000 description 1
- 230000002744 anti-aggregatory effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000000924 antiasthmatic agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 230000007883 bronchodilation Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000002498 deadly effect Effects 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000002405 diagnostic procedure Methods 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 210000003017 ductus arteriosus Anatomy 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 229940001440 flolan Drugs 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- BCQZXOMGPXTTIC-UHFFFAOYSA-N halothane Chemical compound FC(F)(F)C(Cl)Br BCQZXOMGPXTTIC-UHFFFAOYSA-N 0.000 description 1
- 229960003132 halothane Drugs 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 210000005246 left atrium Anatomy 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940100630 metacresol Drugs 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 208000005907 mitral valve insufficiency Diseases 0.000 description 1
- 208000006887 mitral valve stenosis Diseases 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000002663 nebulization Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 230000003836 peripheral circulation Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003173 prostaglandin H2 derivatives Chemical class 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 230000009325 pulmonary function Effects 0.000 description 1
- 230000008695 pulmonary vasoconstriction Effects 0.000 description 1
- 230000010349 pulsation Effects 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 201000004193 respiratory failure Diseases 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 239000004945 silicone rubber Substances 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 206010042772 syncope Diseases 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 229960003279 thiopental Drugs 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000007492 two-way ANOVA Methods 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- 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
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- 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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dispersion Chemistry (AREA)
- Otolaryngology (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12499999P | 1999-03-18 | 1999-03-18 | |
| US124999P | 1999-03-18 | ||
| PCT/US2000/040040 WO2000054758A2 (en) | 1999-03-18 | 2000-03-17 | Method for delivering benzidine prostaglandins by inhalation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60004181D1 DE60004181D1 (de) | 2003-09-04 |
| DE60004181T2 true DE60004181T2 (de) | 2004-04-15 |
Family
ID=22417774
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60004181T Expired - Lifetime DE60004181T2 (de) | 1999-03-18 | 2000-03-17 | Behandlung der pulmonalen hypertension durch inhalation von benzinden-prostaglandine |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US6521212B1 (OSRAM) |
| EP (1) | EP1161234B1 (OSRAM) |
| JP (2) | JP4819224B2 (OSRAM) |
| KR (1) | KR100750384B1 (OSRAM) |
| CN (1) | CN1196479C (OSRAM) |
| AT (1) | ATE245979T1 (OSRAM) |
| AU (1) | AU4082700A (OSRAM) |
| CA (1) | CA2365890C (OSRAM) |
| DE (1) | DE60004181T2 (OSRAM) |
| DK (1) | DK1161234T3 (OSRAM) |
| ES (1) | ES2203449T3 (OSRAM) |
| PT (1) | PT1161234E (OSRAM) |
| WO (1) | WO2000054758A2 (OSRAM) |
Families Citing this family (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6521212B1 (en) * | 1999-03-18 | 2003-02-18 | United Therapeutics Corporation | Method for treating peripheral vascular disease by administering benzindene prostaglandins by inhalation |
| DE10163697A1 (de) * | 2001-12-21 | 2003-07-03 | Studiengesellschaft Kohle Mbh | Reversible Speicherung von Wasserstoff mit Hilfe von dotierten Alkalimetallaluminiumhydriden |
| US9808471B2 (en) | 2003-04-16 | 2017-11-07 | Mylan Specialty Lp | Nasal pharmaceutical formulations and methods of using the same |
| US8912174B2 (en) | 2003-04-16 | 2014-12-16 | Mylan Pharmaceuticals Inc. | Formulations and methods for treating rhinosinusitis |
| US7811606B2 (en) | 2003-04-16 | 2010-10-12 | Dey, L.P. | Nasal pharmaceutical formulations and methods of using the same |
| CA2959852A1 (en) * | 2003-05-22 | 2005-01-27 | United Therapeutics Corporation | Compounds and methods for delivery of prostacyclin analogs |
| US20040265238A1 (en) * | 2003-06-27 | 2004-12-30 | Imtiaz Chaudry | Inhalable formulations for treating pulmonary hypertension and methods of using same |
| US7442372B2 (en) | 2003-08-29 | 2008-10-28 | Biomarin Pharmaceutical Inc. | Delivery of therapeutic compounds to the brain and other tissues |
| US8765813B2 (en) * | 2003-12-16 | 2014-07-01 | United Therapeutics Corporation | Use of treprostinil to treat and prevent ischemic lesions |
| DE602004022982D1 (de) * | 2003-12-16 | 2009-10-15 | United Therapeutics Corp | Verwendung von treprostinil zur verbesserung der nierenfunktion |
| US20090124697A1 (en) | 2003-12-16 | 2009-05-14 | United Therapeutics Corporation | Inhalation formulations of treprostinil |
| WO2005099680A2 (en) * | 2004-04-12 | 2005-10-27 | United Therapeutics, Inc. | Use of treprostinil to treat neuropathic diabetic foot ulcers |
| JP2008523090A (ja) * | 2004-12-08 | 2008-07-03 | バイオマリン ファーマシューティカル インコーポレイテッド | 新生児肺高血圧症の治療のための方法および組成物 |
| CA2631740A1 (en) * | 2005-12-05 | 2007-06-14 | Biomarin Pharmaceutical Inc. | Methods and compositions for the treatment of disease |
| US8747897B2 (en) | 2006-04-27 | 2014-06-10 | Supernus Pharmaceuticals, Inc. | Osmotic drug delivery system |
| KR101390579B1 (ko) * | 2006-05-15 | 2014-05-19 | 유나이티드 세러퓨틱스 코오포레이션 | 정량 흡입기를 사용한 트레프로스티닐 투여 |
| DE102006026786A1 (de) | 2006-06-07 | 2007-12-13 | Joachim Kern | Dosierinhalator |
| US20090036465A1 (en) * | 2006-10-18 | 2009-02-05 | United Therapeutics Corporation | Combination therapy for pulmonary arterial hypertension |
| US20100009997A1 (en) * | 2007-01-12 | 2010-01-14 | Biomarin Pharmaceutical Inc. | Method of treating a metabolic or neuropsychiarty disorder with a bh4 derivative prodrug |
| CN102648916A (zh) * | 2007-02-09 | 2012-08-29 | 联合治疗公司 | 用于间质性肺病和哮喘的曲前列尼治疗 |
| EP2252570B1 (en) | 2007-12-17 | 2017-04-05 | United Therapeutics Corporation | An improved process to prepare treprostinil, the active ingredient in remodulin ® |
| KR20110010753A (ko) | 2008-05-08 | 2011-02-07 | 유나이티드 세러퓨틱스 코오포레이션 | 트레프로스티닐 일수화물 |
| EP2330893A4 (en) * | 2008-09-25 | 2013-01-09 | Aradigm Corp | DEEP PULMONARY ADMINISTRATION OF TREPROSTINIL |
| KR101544246B1 (ko) * | 2009-05-07 | 2015-08-12 | 유나이티드 세러퓨틱스 코오포레이션 | 프로스타시클린 유사체의 고체 제제 |
| CN102883722B (zh) | 2010-03-15 | 2014-11-05 | 联合治疗公司 | 用于肺动脉高血压的治疗 |
| EP2576492B1 (en) | 2010-06-03 | 2017-09-20 | United Therapeutics Corporation | Treprostinil production |
| JP5580491B2 (ja) | 2011-03-02 | 2014-08-27 | ユナイテッド セラピューティクス コーポレイション | トレプロスチニル製造のための中間体の合成 |
| CN103193626B (zh) | 2012-01-10 | 2016-05-11 | 上海天伟生物制药有限公司 | 一种前列腺素类似物的晶型及其制备方法和用途 |
| CN103193627B (zh) | 2012-01-10 | 2016-04-20 | 上海天伟生物制药有限公司 | 一种前列腺素类似物的晶型及其制备方法和用途 |
| US9387214B2 (en) | 2012-01-13 | 2016-07-12 | United Therapeutics Corporation | Method of identifying therapies for pulmonary hypertension |
| KR20150089087A (ko) * | 2012-11-30 | 2015-08-04 | 인스메드 인코포레이티드 | 프로스타사이클린 조성물 및 이를 이용하기 위한 방법 |
| CA3212313A1 (en) | 2013-03-14 | 2014-10-02 | United Therapeutics Corporation | Solid forms of treprostinil |
| CN109608326A (zh) | 2013-03-15 | 2019-04-12 | 联合治疗公司 | 曲前列环素的盐 |
| CA2908244C (en) | 2013-03-25 | 2021-04-20 | United Therapeutics Corporation | Process of making prostacyclin compounds with linker thiol and pegylated forms |
| BR112016009207B1 (pt) | 2013-10-25 | 2022-11-22 | Insmed Incorporated | Compostos de prostaciclina |
| JP2017517550A (ja) | 2014-06-13 | 2017-06-29 | ユナイテッド セラピューティクス コーポレイション | トレプロスチニル製剤 |
| EP3209415B1 (en) | 2014-10-20 | 2020-02-19 | United Therapeutics Corporation | Synthesis of intermediates for producing prostacyclin derivatives |
| CA2967385C (en) | 2014-11-18 | 2023-05-16 | Insmed Incorporated | Methods of manufacturing treprostinil and treprostinil derivative prodrugs |
| IL252577B (en) | 2014-12-03 | 2022-07-01 | Steadymed Ltd | Preservative-free treprostinil formulations and methods and devices for use with same |
| RU2593016C2 (ru) * | 2014-12-15 | 2016-07-27 | Федеральное государственное бюджетное учреждение науки Институт теоретической и прикладной механики им. С.А. Христиановича Сибирского отделения Российской академии наук (ИТПМ СО РАН) | Способ лечения артериальной гипертензии путем ингаляционного введения аэрозоля гипотензивного препарата |
| IL262720B2 (en) | 2016-05-05 | 2024-06-01 | Liquidia Tech Inc | Dry powder treprostinil for the treatment of pulmonary hypertension |
| EP3515430A1 (en) | 2016-09-26 | 2019-07-31 | United Therapeutics Corporation | Treprostinil prodrugs |
| CN110381951A (zh) | 2016-12-14 | 2019-10-25 | 瑞必治公司 | 用于治疗肺性高血压和其他肺病症的方法及组合物 |
| US10799653B2 (en) | 2017-01-09 | 2020-10-13 | United Therapeutics Corporation | Aerosol delivery device and method for manufacturing and operating the same |
| US10702495B2 (en) | 2017-02-20 | 2020-07-07 | Nexien Biopharma, Inc. | Method and compositions for treating dystrophies and myotonia |
| EP3498283A1 (en) | 2017-12-14 | 2019-06-19 | Ipsol AG | Glycosidic derivatives of treprostinil |
| ES2976468T3 (es) | 2018-09-18 | 2024-08-01 | Lilly Co Eli | Sal de treprostinil erbumina |
| US10883084B2 (en) | 2018-10-05 | 2021-01-05 | Xenotherapeutics, Inc. | Personalized cells, tissues, and organs for transplantation from a humanized, bespoke, designated-pathogen free, (non-human) donor and methods and products relating to same |
| CA3114681A1 (en) | 2018-10-05 | 2020-04-09 | Xenotherapeutics, Inc. | Xenotransplantation products and methods |
| KR20220002600A (ko) | 2019-04-29 | 2022-01-06 | 인스메드 인코포레이티드 | 트레프로스티닐 전구약물의 건조 분말 조성물 및 이의 사용 방법 |
| EP3750528A1 (en) | 2019-06-11 | 2020-12-16 | Nexien Biopharma, Inc. | Compositions for treating dystrophies and myotonia |
| CA3149358A1 (en) | 2019-08-23 | 2021-03-04 | United Therapeutics Corporation | Treprostinil prodrugs |
| US11339110B2 (en) | 2019-12-19 | 2022-05-24 | Chirogate International Inc. | Efficient crystallization process for preparing ultrapure Treprostinil and crystal prepared therefrom |
| IL296567A (en) | 2020-04-17 | 2022-11-01 | United Therapeutics Corp | Terfostinil for use in the treatment of interstitial lung disease |
| US11793780B2 (en) | 2020-06-09 | 2023-10-24 | United Therapeutics Corporation | Prodrugs of treprosiinil |
| US11447440B2 (en) | 2020-10-29 | 2022-09-20 | Chirogate International Inc. | Treprostinil monohydrate crystals and methods for preparation thereof |
| CN117062605A (zh) | 2020-12-14 | 2023-11-14 | 联合治疗公司 | 使用曲前列环素前药治疗疾病的方法 |
| CA3209987A1 (en) | 2021-03-03 | 2022-09-09 | Hitesh Batra | A dry powder composition of trestinil and its prodrug thereof and further comprising comprising (e)-3,6-bis[4-(n-carbonyl-2-propenyl)amidobutyl]-2,5-diketopiperazine (fdkp) |
| US20230263807A1 (en) | 2022-02-08 | 2023-08-24 | United Therapeutics Corporation | Treprostinil iloprost combination therapy |
| JP2025515512A (ja) | 2022-04-29 | 2025-05-15 | 兆科薬業（広州）有限公司 | トレプロスチニルソフトミスト吸入剤 |
| IL322117A (en) | 2023-01-18 | 2025-09-01 | United Therapeutics Corp | Treatment of pulmonary arterial hypertension |
| WO2024155752A1 (en) | 2023-01-19 | 2024-07-25 | United Therapeutics Corporation | Treprostinil analogs |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4338457A (en) * | 1980-02-28 | 1982-07-06 | The Upjohn Company | Composition and process |
| US4306075A (en) | 1980-03-28 | 1981-12-15 | The Upjohn Company | Composition and process |
| US4306076A (en) * | 1980-04-23 | 1981-12-15 | The Upjohn Company | Inter-phenylene CBA compounds |
| JPS5795920A (en) * | 1980-12-04 | 1982-06-15 | Teijin Ltd | Remedy for respiratory disease |
| US4349689A (en) * | 1980-12-22 | 1982-09-14 | The Upjohn Company | Methano carbacyclin analogs |
| CA1241324A (en) | 1984-03-08 | 1988-08-30 | Paul A. Aristoff | Interphenylene carbacyclin derivatives |
| ZA851337B (en) * | 1984-03-08 | 1985-10-30 | Upjohn Co | Interphenylene carbacyclin derivatives |
| AU587472B2 (en) * | 1985-05-22 | 1989-08-17 | Liposome Technology, Inc. | Liposome inhalation method and system |
| GB8814438D0 (en) | 1988-06-17 | 1988-07-20 | Wellcome Found | Compounds for use in medicine |
| ES2045437T3 (es) * | 1988-06-17 | 1994-01-16 | Wellcome Found | Analogos de prostaglandinas para empleo en medicina. |
| JP2704546B2 (ja) * | 1989-04-04 | 1998-01-26 | 光利 太良 | Ａｔｌｌ治療用吸入剤 |
| US5190972A (en) * | 1992-01-27 | 1993-03-02 | The University Of Melbourne | Method of combatting cyclosporine organ toxicity with prostaglandin analogs |
| DE69332240T2 (de) * | 1992-06-12 | 2003-04-10 | Teijin Ltd., Osaka | Ultrafeines pulver zur inhalation und dessen herstellung |
| EP1045695B1 (en) * | 1997-11-14 | 2004-03-24 | United Therapeutics Corporation | Use of 9-deoxy-2', 9-alpha-methano-3- oxa-4,5,6- trinor-3, 7-(1',3'-interphenylene) -13,14-dihydro- prostaglandin f 1? to treat peripheral vascular disease |
| US6521212B1 (en) * | 1999-03-18 | 2003-02-18 | United Therapeutics Corporation | Method for treating peripheral vascular disease by administering benzindene prostaglandins by inhalation |
-
2000
- 2000-03-15 US US09/525,471 patent/US6521212B1/en not_active Expired - Lifetime
- 2000-03-17 DK DK00920253T patent/DK1161234T3/da active
- 2000-03-17 ES ES00920253T patent/ES2203449T3/es not_active Expired - Lifetime
- 2000-03-17 KR KR1020017011610A patent/KR100750384B1/ko not_active Expired - Lifetime
- 2000-03-17 DE DE60004181T patent/DE60004181T2/de not_active Expired - Lifetime
- 2000-03-17 EP EP00920253A patent/EP1161234B1/en not_active Expired - Lifetime
- 2000-03-17 CA CA2365890A patent/CA2365890C/en not_active Expired - Lifetime
- 2000-03-17 WO PCT/US2000/040040 patent/WO2000054758A2/en not_active Ceased
- 2000-03-17 JP JP2000604834A patent/JP4819224B2/ja not_active Expired - Lifetime
- 2000-03-17 AT AT00920253T patent/ATE245979T1/de active
- 2000-03-17 AU AU40827/00A patent/AU4082700A/en not_active Abandoned
- 2000-03-17 CN CNB008051089A patent/CN1196479C/zh not_active Expired - Lifetime
- 2000-03-17 PT PT00920253T patent/PT1161234E/pt unknown
-
2002
- 2002-08-06 US US10/212,149 patent/US6756033B2/en not_active Expired - Lifetime
-
2011
- 2011-05-30 JP JP2011119894A patent/JP2011201907A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CA2365890C (en) | 2010-09-21 |
| US6756033B2 (en) | 2004-06-29 |
| WO2000054758A2 (en) | 2000-09-21 |
| KR100750384B1 (ko) | 2007-08-17 |
| JP4819224B2 (ja) | 2011-11-24 |
| CA2365890A1 (en) | 2000-09-21 |
| AU4082700A (en) | 2000-10-04 |
| KR20010108352A (ko) | 2001-12-07 |
| ES2203449T3 (es) | 2004-04-16 |
| EP1161234A2 (en) | 2001-12-12 |
| DK1161234T3 (da) | 2003-11-24 |
| DE60004181D1 (de) | 2003-09-04 |
| US20030053958A1 (en) | 2003-03-20 |
| JP2011201907A (ja) | 2011-10-13 |
| EP1161234B1 (en) | 2003-07-30 |
| US6521212B1 (en) | 2003-02-18 |
| CN1196479C (zh) | 2005-04-13 |
| WO2000054758A3 (en) | 2001-02-08 |
| JP2002539154A (ja) | 2002-11-19 |
| PT1161234E (pt) | 2003-12-31 |
| ATE245979T1 (de) | 2003-08-15 |
| CN1379665A (zh) | 2002-11-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60004181T2 (de) | Behandlung der pulmonalen hypertension durch inhalation von benzinden-prostaglandine | |
| DE60027985T2 (de) | Behandlung von Lungenhochdruck | |
| JP7621220B2 (ja) | 疾患の処置のための鼻腔内エピネフリン製剤及び方法 | |
| DE69133584T2 (de) | Vorrichtung zum Behandeln einen Lungengefässverengung und von Asthma | |
| US20220008436A1 (en) | Treprostinil administration by inhalation | |
| CA2043077C (en) | Prostaglandin analogues for use in medicine | |
| DE69822665T2 (de) | Verwendung von 9-desoxy-2',9-alpha-methano-3-oxa-4,5,6-trinor-3,7-(1',3'-interphenylen)-13,14-dihydroprostaglandin-f1 zur behandlung von peripheren vaskulären erkrankungen | |
| DE69428351T3 (de) | Systemische effekte der inhalation von stickstoffoxid | |
| DE69533190T2 (de) | Behandlung von pulmonaler vasokonstriktion und asthma | |
| EP2110126B9 (de) | Inhalative und instillative Verwendung von semifluorierten Alkanen als Wirkstoffträger im intrapulmonalen Bereich | |
| DE69526425T2 (de) | Verwendung von mometasone-furoat zur behandlung von luftweg- und lungenerkrankungen | |
| DE69326849T2 (de) | Verwendung von humanem Atrio-natriuretischem Peptid zur Herstellung eines Medikaments zur Behandlung des Atemunwohlseinsyndroms bei Erwachsenen | |
| Stirt | Aminophylline is a diazepam antagonist | |
| DE68904358T2 (de) | Prostaglandinanaloge zur verwendung in der medizin. | |
| DE3315356A1 (de) | Verwendung von prostaglandinanalogen | |
| EP1526870A1 (de) | Neue kombination von glucocorticoiden und pde-4-inhibitoren zur behandlung von atemwegserkrankungen, allergischen erkrankungen, asthma und copd | |
| DE112019000683T5 (de) | Intranasale epinephrin-formulierungen und verfahren zur behandlung von erkrankungen | |
| DE19519056A1 (de) | Verwendung von Antidepressiva zur Behandlung von Asthma und/oder Atemwegserkrankungen mittels inhalatorischer Applikation | |
| DE60301862T2 (de) | Kombinationsbehandlung bei akutem myokardinfarkt | |
| DE68907976T2 (de) | Verwendung eines Thromboxan-A2-Rezeptorantagonist zur Herstellung eines Arzeneimittels zur Behandlung pulmonarer Hypertonie, die durch Protamin-induzierte Neutralisation von Heparin verursacht wird. | |
| EP2581082B1 (de) | Pharmazeutische Zusammensetzung zur Behandlung von Status asthmaticus | |
| DE3880943T2 (de) | Verwendung von thromboxan-a2-antagonisten zur herstellung eines arzneimittels zur wiederherstellung von post-ischaemischer myokard-dysfunktion. | |
| DE60202299T2 (de) | Pharmazeutische zusammensetzung enthaltend salmeterol und budesonid zur behandlung von atemkrankheiten | |
| DE69128780T2 (de) | Verwendung von adenosine und adenosinederivate zur anästhesie | |
| CN120227329A (zh) | 用于治疗肺动脉高压的药物制剂及其制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |