DK3193835T3 - Flydende inhalationsformulering, der omfatter RPL554 - Google Patents
Flydende inhalationsformulering, der omfatter RPL554 Download PDFInfo
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- DK3193835T3 DK3193835T3 DK15770593.0T DK15770593T DK3193835T3 DK 3193835 T3 DK3193835 T3 DK 3193835T3 DK 15770593 T DK15770593 T DK 15770593T DK 3193835 T3 DK3193835 T3 DK 3193835T3
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- DK
- Denmark
- Prior art keywords
- rpl554
- pharmaceutical composition
- liquid pharmaceutical
- concentration
- particles
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- CSOBIBXVIYAXFM-BYNJWEBRSA-N ensifentrine Chemical compound c-12cc(OC)c(OC)cc2CCn(c(n2CCNC(N)=O)=O)c-1c\c2=N/c1c(C)cc(C)cc1C CSOBIBXVIYAXFM-BYNJWEBRSA-N 0.000 title claims abstract description 131
- 239000007788 liquid Substances 0.000 title claims abstract description 62
- 239000000203 mixture Substances 0.000 title claims description 82
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- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 62
- 241001465754 Metazoa Species 0.000 claims abstract description 19
- 238000011282 treatment Methods 0.000 claims abstract description 18
- 239000003085 diluting agent Substances 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- CSOBIBXVIYAXFM-UHFFFAOYSA-N rpl-554 Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C(N2CCNC(N)=O)=O)C1=CC2=NC1=C(C)C=C(C)C=C1C CSOBIBXVIYAXFM-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000009826 distribution Methods 0.000 claims description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 22
- 208000006673 asthma Diseases 0.000 claims description 19
- 239000006199 nebulizer Substances 0.000 claims description 16
- 239000011780 sodium chloride Substances 0.000 claims description 16
- 239000004094 surface-active agent Substances 0.000 claims description 15
- -1 2,4,6-trimethylphenylimino Chemical group 0.000 claims description 13
- 239000000872 buffer Substances 0.000 claims description 12
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 11
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 11
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 11
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 10
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 8
- 239000008363 phosphate buffer Substances 0.000 claims description 8
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 8
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- 239000003149 muscarinic antagonist Substances 0.000 claims description 4
- XZIIFPSPUDAGJM-UHFFFAOYSA-N 6-chloro-2-n,2-n-diethylpyrimidine-2,4-diamine Chemical compound CCN(CC)C1=NC(N)=CC(Cl)=N1 XZIIFPSPUDAGJM-UHFFFAOYSA-N 0.000 claims description 3
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 claims description 3
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 3
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- 206010039085 Rhinitis allergic Diseases 0.000 claims description 3
- LWZFANDGMFTDAV-BURFUSLBSA-N [(2r)-2-[(2r,3r,4s)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O LWZFANDGMFTDAV-BURFUSLBSA-N 0.000 claims description 3
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- BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 claims description 2
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- GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 2
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- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
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- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
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- IYFATESGLOUGBX-YVNJGZBMSA-N Sorbitan monopalmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O IYFATESGLOUGBX-YVNJGZBMSA-N 0.000 description 1
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- IJCWFDPJFXGQBN-RYNSOKOISA-N [(2R)-2-[(2R,3R,4S)-4-hydroxy-3-octadecanoyloxyoxolan-2-yl]-2-octadecanoyloxyethyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCCCCCCCCCCCC IJCWFDPJFXGQBN-RYNSOKOISA-N 0.000 description 1
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- SYELZBGXAIXKHU-UHFFFAOYSA-N dodecyldimethylamine N-oxide Chemical compound CCCCCCCCCCCC[N+](C)(C)[O-] SYELZBGXAIXKHU-UHFFFAOYSA-N 0.000 description 1
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- NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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Claims (15)
1. Flydende, farmaceutisk sammensætning, der er egnet til indgivelse via inhalation, hvilken sammensætning omfatter en fortynder og en suspension af partikler af 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1 -a]isoquinolin-4-on (RPL554) eller et farmaceutisk acceptabelt salt deraf, hvor partiklerne af RPL554 har en partikelstørrelsesfordeling med en Dv50-(median volumenpartikelstørrelse) værdi på fra 0,2 pm til 5 pm, og hvor den flydende, farmaceutiske sammensætning ikke omfatter en mængde over 0,1 vægt-% i alt af en p2-adrenerg receptoragonist og en muskarin-receptorantagonist.
2. Flydende, farmaceutisk sammensætning ifølge krav 1, hvor sammensætningen ikke omfatter en p2-adrenerg receptoragonist eller en muskarin-receptorantagonist.
3. Flydende, farmaceutisk sammensætning ifølge krav 1 eller krav 2, hvor partiklerne af RPL554 har en partikelstørrelsesfordeling med en Dv50-værdi på fra 0,7 pm til 2,5 pm.
4. Flydende, farmaceutisk sammensætning ifølge et hvilket som helst af de foregående krav, hvor koncentrationen af partikler af RPL554 i den flydende, farmaceutisk sammensætning er fra 0,01 mg/mL til 40 mg/mL.
5. Flydende, farmaceutisk sammensætning ifølge et hvilket som helst af de foregående krav, hvor sammensætningen har et pH på fra 6 til 8.
6. Flydende, farmaceutisk sammensætning ifølge et hvilket som helst af de foregående krav, der endvidere omfatter ét eller flere overfladeaktive midler, fortrinsvis hvor det ene eller flere overfladeaktive midler er udvalgt fra ét eller flere ikke-ioniske overfladeaktive midler, mere fortrinsvis hvor det ene eller flere overfladeaktive midler er udvalgt fra polyoxyethylenglycolsorbitanalkylestere og sorbitanalkylestere.
7. Flydende, farmaceutisk sammensætning ifølge et hvilket som helst af de foregående krav, der endvidere omfatter én eller flere buffere, fortrinsvis hvor den ene eller flere buffere er udvalgt fra citrat- eller phosphatbuffere.
8. Flydende, farmaceutisk sammensætning ifølge et hvilket som helst af de foregående krav, hvilken sammensætning omfatter: (a) partiklerne af RLP554 ved en koncentration på fra 0,01 mg/mL til 40 mg/mL; (b) ét eller flere overfladeaktive midler ved en koncentration på fra 0,01 mg/mL til 5 mg/mL og (c) en buffer ved en koncentration på fra 5 mg/mL til 20 mg/mL.
9. Flydende, farmaceutisk sammensætning ifølge et hvilket som helst af de foregående krav, hvor sammensætningen endvidere omfatter et tonicitetsjusteringsmiddel, eventuelt hvor tonicitetsjusteringsmidlet er natriumchlorid.
10. Flydende, farmaceutisk sammensætning ifølge et hvilket som helst af de foregående krav, hvor fortynderen er vand.
11. Flydende, farmaceutisk sammensætning ifølge et hvilket som helst af de foregående krav, hvilken sammensætning omfatter: (a) partiklerne af RLP554 ved en koncentration på 0,01 mg/mL til 30 mg/mL; (b) en polyoxyethylenglycolsorbitanalkylester ved en koncentration på fra 0,1 mg/mL til 2 mg/mL; (c) en sorbitanalkylester ved en koncentration på fra 0,01 mg/mL til 0,1 mg/mL; (d) en første phosphatbufferkomponent ved en koncentration på fra 5 mg/mL til 10 mg/mL; (e) en anden phosphatbufferkomponent ved en koncentration på fra 5 mg/mL til 10 mg/mL og (f) et tonicitetsjusteringsmiddel ved en koncentration på fra 2 mg/mL til 8 mg/mL, fortrinsvis hvor sammensætningen omfatter: (a) partiklerne af RLP554 ved en koncentration på 0,05 mg/mL til 25 mg/mL; (b) polyoxyethylen- (20) sorbitanmonolaurat (Polysorbat 20, Tween 20) ved en koncentration på fra 0,1 mg/mL til 2 mg/mL; (c) sorbitanmonolaurat (Span 20) ved en koncentration på fra 0,01 mg/mL til 0,1 mg/mL; (d) mononatriumphosphatmonohydrat ved en koncentration på fra 5 mg/mL til 10 mg/mL; (e) vandfrit, dibasisk natriumphosphat ved en koncentration på fra 5 mg/mL til 10 mg/mL og (f) natriumchlorid ved en koncentration på fra 2 mg/mL til 8 mg/mL.
12. Flydende, farmaceutisk sammensætning ifølge et hvilket som helst af de foregående krav, der er egnet til indgivelse ved hjælp af en forstøver.
13. Forstøver, der omfatter en flydende, farmaceutisk sammensætning, der er egnet til indgivelse via inhalation, og som omfatter en fortynder og en suspension af partikler af 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-on (RPL554) eller et farmaceutisk acceptabelt salt deraf, hvor partiklerne af RPL554 har en partikelstørrelsesfordeling med en Dv50- (median volumenpartikelstørrelse) værdi på fra 0,2 pm til 5 pm.
14. Flydende, farmaceutisk sammensætning ifølge et hvilket som helst af kravene 1 til 12 til anvendelse i behandlingen af menneske- eller dyrekroppen.
15. Flydende, farmaceutisk sammensætning ifølge et hvilket som helst af kravene 1 til 12 til anvendelse i behandling eller forebyggelse af en sygdom eller tilstand udvalgt fra astma, allergisk astma, høfeber, allergisk rinitis, bronkitis, emfysem, bronkiektasi, kronisk obstruktiv lungesygdom (COPD), adult respiratorisk distress-syndrom (ARDS), steroidresistent astma, svær astma, pædiatrisk astma, cystisk fibrose, lungefibrose, pulmonal fibrose, interstitiel lungesygdom, hudforstyrrelser, atopisk dermatitis, psoriasis, øjeninflammation, cerebral iskæmi, inflammatoriske sygdomme og autoimmune sygdomme, fortrinsvis hvor sygdommen eller tilstanden er kronisk obstruktiv lungesygdom (COPD).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1416274.7A GB201416274D0 (en) | 2014-09-15 | 2014-09-15 | Formulation |
| GBGB1504662.6A GB201504662D0 (en) | 2015-03-19 | 2015-03-19 | Formulation |
| PCT/GB2015/052668 WO2016042313A1 (en) | 2014-09-15 | 2015-09-15 | Liquid inhalation formulation comprising rpl554 |
Publications (1)
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| DK3193835T3 true DK3193835T3 (da) | 2018-05-07 |
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| DK15770593.0T DK3193835T3 (da) | 2014-09-15 | 2015-09-15 | Flydende inhalationsformulering, der omfatter RPL554 |
| DK17207623.4T DK3332767T3 (da) | 2014-09-15 | 2015-09-15 | Flydende inhalationsformulering, der omfatter RPL554 |
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| DK17207623.4T DK3332767T3 (da) | 2014-09-15 | 2015-09-15 | Flydende inhalationsformulering, der omfatter RPL554 |
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| PL3231444T3 (pl) | 2014-05-12 | 2020-05-18 | Verona Pharma Plc | Nowe leczenie |
| HUE055527T2 (hu) * | 2014-09-15 | 2021-12-28 | Verona Pharma Plc | RPL554-t tartalmazó folyékony inhalációs készítmény |
| GB201502260D0 (en) | 2015-02-11 | 2015-04-01 | Verona Pharma Plc | Salt of Pyrimido[6,1-A]Isoquinolin-4-one compound |
| JP6814754B2 (ja) | 2015-07-24 | 2021-01-20 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | Ｂａｃｅ１阻害剤ペプチド |
| GB201613054D0 (en) | 2016-07-28 | 2016-09-14 | Verona Pharma Plc | New compound and process |
| GB2578093B (en) | 2018-10-09 | 2020-11-18 | Verona Pharma Plc | Liquid pharmaceutical composition comprising RPL554 and HFA-134A |
| JP6994061B2 (ja) * | 2019-02-15 | 2022-01-14 | ノバルティス アーゲー | ４－（７－ヒドロキシ－２－イソプロピル－４－オキソ－４ｈ－キナゾリン－３－イル）－ベンゾニトリルの製剤 |
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| EP4092025B9 (en) * | 2020-01-15 | 2024-11-06 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Pharmaceutical composition of tricyclic pde3/pde4 dual inhibitor compound |
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| AU2023324461A1 (en) * | 2022-08-08 | 2025-02-06 | Verona Pharma Plc | Ensifentrine (rpl-554) for decreasing the frequency and/or severity of copd exacerbations |
| CA3263545A1 (en) * | 2022-08-08 | 2024-02-15 | Verona Pharma Plc | LIQUID PHARMACEUTICAL COMPOSITION |
| JP2025534762A (ja) * | 2022-10-28 | 2025-10-17 | 江蘇恒瑞医薬股▲ふん▼有限公司 | イソキノリノン系化合物を含む医薬組成物及びその調製方法 |
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| US20250249008A1 (en) * | 2024-02-07 | 2025-08-07 | Verona Pharma Plc | Pharmaceutical compositions of ensifentrine for chronic obstructive pulmonary disease |
| US20250249007A1 (en) * | 2024-02-07 | 2025-08-07 | Verona Pharma Plc | Pharmaceutical compositions of ensifentrine for chronic obstructive pulmonary disease |
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| WO2000058308A1 (en) | 1999-03-31 | 2000-10-05 | Vernalis Limited | DERIVATIVES OF PYRIMIDO[6,1-a]ISOQUINOLIN-4-ONE |
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| GB0122031D0 (en) * | 2001-09-12 | 2001-10-31 | Pfizer Ltd | Use of pde4 inhibitors in a dry powder inhaler |
| US7579505B2 (en) | 2004-12-17 | 2009-08-25 | Cipla Limited | Crystalline levosalbutamol sulphate and polymorphic forms thereof |
| ITMI20051999A1 (it) | 2005-10-21 | 2007-04-22 | Eratech S R L | Formulazioni inalatorie di farmaci in fora di polvere secca per somministrazione come tale o con nebulizzatore e dotate di elevata erogabilita' respirabilita' e stabilita' |
| BR112012032332A2 (pt) | 2010-06-22 | 2016-11-08 | Chiesi Farma Spa | composto, uso de um composto, composição farmacêutica, combinação de um composto e dispositivo |
| DK2603509T3 (da) | 2010-08-09 | 2014-09-08 | Verona Pharma Plc | KRYSTALLINSK FORM AF PYRIMIDIO [6,1- a] ISOQUINOLIN-4-ON-FORBINDELSE |
| CN103732213A (zh) * | 2011-06-07 | 2014-04-16 | 帕里昂科学公司 | 治疗方法 |
| US8945605B2 (en) | 2011-06-07 | 2015-02-03 | Parion Sciences, Inc. | Aerosol delivery systems, compositions and methods |
| EP2647627A1 (en) * | 2012-04-02 | 2013-10-09 | Almirall, S.A. | Salts of 5-[(1r)-2-({2-[4-(2,2-difluoro-2-phenylethoxy)phenyl] ethyl}amino)-1-hydroxyethyl]-8-hydroxyquinolin-2(1h)-one. |
| WO2014037727A1 (en) | 2012-09-06 | 2014-03-13 | Verona Pharma Plc | Carcainium salts |
| PT2968312T (pt) | 2013-03-15 | 2018-04-19 | Verona Pharma Plc | Combinação de fármacos |
| JP6702634B2 (ja) * | 2014-03-11 | 2020-06-03 | エルジー エレクトロニクス インコーポレイティド | 無線通信システムにおいて装置対装置端末のディスカバリ信号伝送方法及び装置 |
| PL3231444T3 (pl) | 2014-05-12 | 2020-05-18 | Verona Pharma Plc | Nowe leczenie |
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