ZA200409793B - A buffered, liquid nicotine composition for pulmonary administration - Google Patents
A buffered, liquid nicotine composition for pulmonary administration Download PDFInfo
- Publication number
- ZA200409793B ZA200409793B ZA200409793A ZA200409793A ZA200409793B ZA 200409793 B ZA200409793 B ZA 200409793B ZA 200409793 A ZA200409793 A ZA 200409793A ZA 200409793 A ZA200409793 A ZA 200409793A ZA 200409793 B ZA200409793 B ZA 200409793B
- Authority
- ZA
- South Africa
- Prior art keywords
- nicotine
- pharmaceutical formulation
- subject
- liquid pharmaceutical
- methods
- Prior art date
Links
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 title claims description 279
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 title claims description 276
- 229960002715 nicotine Drugs 0.000 title claims description 274
- 239000007788 liquid Substances 0.000 title claims description 97
- 239000000203 mixture Substances 0.000 title claims description 69
- 230000002685 pulmonary effect Effects 0.000 title claims description 16
- 238000000034 method Methods 0.000 claims description 106
- 239000008194 pharmaceutical composition Substances 0.000 claims description 92
- 235000002637 Nicotiana tabacum Nutrition 0.000 claims description 83
- 241000208125 Nicotiana Species 0.000 claims description 82
- 230000000391 smoking effect Effects 0.000 claims description 78
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 58
- 210000004369 blood Anatomy 0.000 claims description 38
- 239000008280 blood Substances 0.000 claims description 38
- 239000000779 smoke Substances 0.000 claims description 38
- 230000009467 reduction Effects 0.000 claims description 36
- 210000004072 lung Anatomy 0.000 claims description 32
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 30
- 238000009472 formulation Methods 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 239000000126 substance Substances 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 20
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 18
- 238000010521 absorption reaction Methods 0.000 claims description 18
- 238000004519 manufacturing process Methods 0.000 claims description 18
- 239000000463 material Substances 0.000 claims description 18
- 210000000214 mouth Anatomy 0.000 claims description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 15
- 239000000443 aerosol Substances 0.000 claims description 15
- 150000003839 salts Chemical group 0.000 claims description 14
- 239000012458 free base Substances 0.000 claims description 13
- 239000006172 buffering agent Substances 0.000 claims description 12
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- 239000007921 spray Substances 0.000 claims description 11
- 239000003826 tablet Substances 0.000 claims description 11
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- 235000015218 chewing gum Nutrition 0.000 claims description 10
- 230000001105 regulatory effect Effects 0.000 claims description 10
- 238000002560 therapeutic procedure Methods 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 239000011780 sodium chloride Substances 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 230000029219 regulation of pH Effects 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 7
- 239000000654 additive Substances 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- -1 mono-carbonate Chemical compound 0.000 claims description 7
- 239000007922 nasal spray Substances 0.000 claims description 7
- 239000001117 sulphuric acid Substances 0.000 claims description 7
- 235000011149 sulphuric acid Nutrition 0.000 claims description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 238000001990 intravenous administration Methods 0.000 claims description 6
- 239000007791 liquid phase Substances 0.000 claims description 6
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- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 4
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- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
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- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 claims description 2
- 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 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-M L-tartrate(1-) Chemical compound OC(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-M 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
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- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 2
- 239000000920 calcium hydroxide Substances 0.000 claims description 2
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 2
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000292 calcium oxide Substances 0.000 claims description 2
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims description 2
- 125000002091 cationic group Chemical group 0.000 claims description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
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- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
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- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 claims description 2
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
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Classifications
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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
- A61K9/007—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
- A61K31/435—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
- A61K31/465—Nicotine; Derivatives thereof
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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| SE521512C2 (sv) | 2001-06-25 | 2003-11-11 | Niconovum Ab | Anordning för administrering av en substans till främre delen av en individs munhåla |
| EP1578422B1 (en) | 2002-12-20 | 2007-04-11 | NicoNovum AB | A physically and chemically stable nicotine and micorcrystalline cellulose containing particulate material |
| CN100381083C (zh) | 2003-04-29 | 2008-04-16 | 韩力 | 一种非可燃性电子喷雾香烟 |
| CN2719043Y (zh) | 2004-04-14 | 2005-08-24 | 韩力 | 雾化电子烟 |
| CA2881078C (en) | 2004-06-24 | 2018-10-02 | Vertex Pharmaceuticals Incorporated | Modulators of atp-binding cassette transporters |
| US20160345631A1 (en) | 2005-07-19 | 2016-12-01 | James Monsees | Portable devices for generating an inhalable vapor |
| LT1993360T (lt) | 2005-12-28 | 2017-06-12 | Vertex Pharmaceuticals Incorporated | N-[2,4-bis(1,1-dimetiletil)-5-hidroksifenil]-1,4-dihidro-4-oksochinolin-3-karboksamido kieta forma |
| US9402809B2 (en) | 2006-03-16 | 2016-08-02 | Niconovum Usa, Inc. | Snuff composition |
| CN201067079Y (zh) | 2006-05-16 | 2008-06-04 | 韩力 | 仿真气溶胶吸入器 |
| US7726320B2 (en) | 2006-10-18 | 2010-06-01 | R. J. Reynolds Tobacco Company | Tobacco-containing smoking article |
| RU2010114732A (ru) * | 2007-09-14 | 2011-10-20 | Вертекс Фармасьютикалз Инкорпорейтед (Us) | Твердые формы n-[2,4-бис(1,1-диметилэтил)-5-гидроксифенил]-1,4-дигидро-4-оксохинолин-3-карбоксамида |
| US20100074949A1 (en) | 2008-08-13 | 2010-03-25 | William Rowe | Pharmaceutical composition and administration thereof |
| US12458635B2 (en) | 2008-08-13 | 2025-11-04 | Vertex Pharmaceuticals Incorporated | Pharmaceutical composition and administrations thereof |
| AT507187B1 (de) | 2008-10-23 | 2010-03-15 | Helmut Dr Buchberger | Inhalator |
| CN201379072Y (zh) | 2009-02-11 | 2010-01-13 | 韩力 | 一种改进的雾化电子烟 |
| SI3330255T1 (sl) | 2009-03-20 | 2021-03-31 | Vertex Pharmaceuticals Incorporated | Postopek izdelave regulatorja transmembranske prevodnosti pri cistični fibrozi |
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| IL294000B (en) | 2019-12-15 | 2022-09-01 | Shaheen Innovations Holding Ltd | Steam inhaler devices |
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| US11730191B2 (en) | 2019-12-15 | 2023-08-22 | Shaheen Innovations Holding Limited | Hookah device |
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| WO2021123866A1 (en) | 2019-12-15 | 2021-06-24 | Shaheen Innovations Holding Limited | Ultrasonic mist inhaler |
| US11666713B2 (en) | 2019-12-15 | 2023-06-06 | Shaheen Innovations Holding Limited | Mist inhaler devices |
| EP3856304B1 (en) | 2019-12-15 | 2023-11-08 | Shaheen Innovations Holding Limited | Ultrasonic mist inhaler |
| US11730193B2 (en) | 2019-12-15 | 2023-08-22 | Shaheen Innovations Holding Limited | Hookah device |
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| GB2030862A (en) * | 1978-04-10 | 1980-04-16 | Smith A | A composition for treating drug addiction such as smoking nicotine-containing products |
| DE3241437A1 (de) * | 1982-11-10 | 1984-05-10 | Ferdinand Prof. Dr.med. 6901 Wilhelmsfeld Schmidt | Mittel zum zwecke der raucherentwoehnung und/oder fuer nebenwirkungsfreien nikotingenuss bei suchtrauchern |
| GB8301659D0 (en) * | 1983-01-21 | 1983-02-23 | Leo Ab | Smoking substitutes |
| US4920989A (en) * | 1985-04-25 | 1990-05-01 | Regents Of The University Of California | Method and apparatus for aiding in the reduction of incidence of tobacco smoking |
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| TR199802305T2 (xx) * | 1996-05-13 | 2002-06-21 | Norvartis Consumer Health S.A. | Yanaktan uygulama y�ntemi. |
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| RU2004139067A (ru) | 2005-08-10 |
| RU2283111C2 (ru) | 2006-09-10 |
| WO2003101454A1 (en) | 2003-12-11 |
| CN100500148C (zh) | 2009-06-17 |
| BR0311451A (pt) | 2005-03-15 |
| DE60329592D1 (de) | 2009-11-19 |
| AU2003243074B2 (en) | 2008-11-20 |
| JP2010280721A (ja) | 2010-12-16 |
| AR039947A1 (es) | 2005-03-09 |
| ATE444753T1 (de) | 2009-10-15 |
| JP2005533770A (ja) | 2005-11-10 |
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| EP1509227A1 (en) | 2005-03-02 |
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| DK1509227T3 (da) | 2010-02-01 |
| JP4745658B2 (ja) | 2011-08-10 |
| CA2487699A1 (en) | 2003-12-11 |
| MXPA04012041A (es) | 2005-08-16 |
| JP5430525B2 (ja) | 2014-03-05 |
| NZ536863A (en) | 2007-05-31 |
| EP1509227B1 (en) | 2009-10-07 |
| CN1658876A (zh) | 2005-08-24 |
| SE0201669D0 (sv) | 2002-06-03 |
| AU2003243074A1 (en) | 2003-12-19 |
| EP1509227B9 (en) | 2010-05-19 |
| IL165195A0 (en) | 2005-12-18 |
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