CA2656823C - Cyanocobalamin low viscosity aqueous formulations for intranasal delivery - Google Patents
Cyanocobalamin low viscosity aqueous formulations for intranasal delivery Download PDFInfo
- Publication number
- CA2656823C CA2656823C CA2656823A CA2656823A CA2656823C CA 2656823 C CA2656823 C CA 2656823C CA 2656823 A CA2656823 A CA 2656823A CA 2656823 A CA2656823 A CA 2656823A CA 2656823 C CA2656823 C CA 2656823C
- Authority
- CA
- Canada
- Prior art keywords
- cyanocobalamin
- solution
- concentration
- spray
- droplets
- 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 - Fee Related
Links
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 title claims abstract description 574
- 235000000639 cyanocobalamin Nutrition 0.000 title claims abstract description 287
- 239000011666 cyanocobalamin Substances 0.000 title claims abstract description 287
- 229960002104 cyanocobalamin Drugs 0.000 title claims abstract description 287
- 239000013011 aqueous formulation Substances 0.000 title description 3
- 239000000243 solution Substances 0.000 claims abstract description 128
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims abstract description 46
- 239000007927 intramuscular injection Substances 0.000 claims abstract description 39
- 238000010255 intramuscular injection Methods 0.000 claims abstract description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 32
- 239000007864 aqueous solution Substances 0.000 claims abstract description 26
- 210000002966 serum Anatomy 0.000 claims abstract description 26
- 230000003028 elevating effect Effects 0.000 claims abstract description 5
- FDJOLVPMNUYSCM-UVKKECPRSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2,7, Chemical compound [Co+3].N#[C-].C1([C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)[N-]\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O FDJOLVPMNUYSCM-UVKKECPRSA-L 0.000 claims abstract 5
- 229940045999 vitamin b 12 Drugs 0.000 claims abstract 5
- 239000007921 spray Substances 0.000 claims description 131
- 239000000203 mixture Substances 0.000 claims description 108
- 238000009472 formulation Methods 0.000 claims description 86
- FDJOLVPMNUYSCM-WZHZPDAFSA-L cobalt(3+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+3].N#[C-].N([C@@H]([C@]1(C)[N-]\C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C(\C)/C1=N/C([C@H]([C@@]1(CC(N)=O)C)CCC(N)=O)=C\C1=N\C([C@H](C1(C)C)CCC(N)=O)=C/1C)[C@@H]2CC(N)=O)=C\1[C@]2(C)CCC(=O)NC[C@@H](C)OP([O-])(=O)O[C@H]1[C@@H](O)[C@@H](N2C3=CC(C)=C(C)C=C3N=C2)O[C@@H]1CO FDJOLVPMNUYSCM-WZHZPDAFSA-L 0.000 claims description 80
- 229930003779 Vitamin B12 Natural products 0.000 claims description 76
- 235000019163 vitamin B12 Nutrition 0.000 claims description 76
- 239000011715 vitamin B12 Substances 0.000 claims description 76
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 65
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 46
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 23
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 23
- 235000011187 glycerol Nutrition 0.000 claims description 22
- 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 claims description 21
- 239000001509 sodium citrate Substances 0.000 claims description 21
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 15
- 239000003755 preservative agent Substances 0.000 claims description 14
- 230000002335 preservative effect Effects 0.000 claims description 13
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims description 12
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 claims description 12
- 229910052753 mercury Inorganic materials 0.000 claims description 12
- 239000003906 humectant Substances 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 7
- 229960004926 chlorobutanol Drugs 0.000 claims description 6
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 5
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 5
- 230000001965 increasing effect Effects 0.000 claims description 5
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 5
- 239000000600 sorbitol Substances 0.000 claims description 5
- 238000000034 method Methods 0.000 abstract description 28
- 238000011282 treatment Methods 0.000 description 49
- 239000000499 gel Substances 0.000 description 38
- YOZNUFWCRFCGIH-BYFNXCQMSA-L hydroxocobalamin Chemical compound O[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O YOZNUFWCRFCGIH-BYFNXCQMSA-L 0.000 description 38
- 238000007918 intramuscular administration Methods 0.000 description 31
- 229940097496 nasal spray Drugs 0.000 description 30
- 239000007922 nasal spray Substances 0.000 description 30
- 235000004867 hydroxocobalamin Nutrition 0.000 description 19
- 239000011704 hydroxocobalamin Substances 0.000 description 19
- 229960001103 hydroxocobalamin Drugs 0.000 description 19
- 208000002670 vitamin B12 deficiency Diseases 0.000 description 17
- 239000007788 liquid Substances 0.000 description 13
- 238000010521 absorption reaction Methods 0.000 description 12
- 239000000047 product Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 229940088594 vitamin Drugs 0.000 description 10
- 229930003231 vitamin Natural products 0.000 description 10
- 235000013343 vitamin Nutrition 0.000 description 10
- 239000011782 vitamin Substances 0.000 description 10
- 239000000443 aerosol Substances 0.000 description 9
- 229960004106 citric acid Drugs 0.000 description 9
- 235000005911 diet Nutrition 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 238000005259 measurement Methods 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 150000003722 vitamin derivatives Chemical class 0.000 description 9
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 8
- 239000006196 drop Substances 0.000 description 8
- 229940029329 intrinsic factor Drugs 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- 230000007812 deficiency Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 210000001331 nose Anatomy 0.000 description 7
- 210000002381 plasma Anatomy 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 210000002850 nasal mucosa Anatomy 0.000 description 6
- 229940087672 nascobal Drugs 0.000 description 6
- 206010025476 Malabsorption Diseases 0.000 description 5
- 208000004155 Malabsorption Syndromes Diseases 0.000 description 5
- 238000000540 analysis of variance Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 208000015943 Coeliac disease Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 230000004913 activation Effects 0.000 description 4
- 230000002950 deficient Effects 0.000 description 4
- 230000000378 dietary effect Effects 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000012423 maintenance Methods 0.000 description 4
- 229940100892 mercury compound Drugs 0.000 description 4
- 150000002731 mercury compounds Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000009593 lumbar puncture Methods 0.000 description 3
- 210000004400 mucous membrane Anatomy 0.000 description 3
- 210000003928 nasal cavity Anatomy 0.000 description 3
- 229940100656 nasal solution Drugs 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 210000003800 pharynx Anatomy 0.000 description 3
- 230000036470 plasma concentration Effects 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 230000028327 secretion Effects 0.000 description 3
- 229960001790 sodium citrate Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 208000004300 Atrophic Gastritis Diseases 0.000 description 2
- 241000972773 Aulopiformes Species 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- 208000031845 Pernicious anaemia Diseases 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 208000016644 chronic atrophic gastritis Diseases 0.000 description 2
- 235000006279 cobamamide Nutrition 0.000 description 2
- 239000011789 cobamamide Substances 0.000 description 2
- ZIHHMGTYZOSFRC-UWWAPWIJSA-M cobamamide Chemical compound C1(/[C@](C)(CCC(=O)NC[C@H](C)OP(O)(=O)OC2[C@H]([C@H](O[C@@H]2CO)N2C3=CC(C)=C(C)C=C3N=C2)O)[C@@H](CC(N)=O)[C@]2(N1[Co+]C[C@@H]1[C@H]([C@@H](O)[C@@H](O1)N1C3=NC=NC(N)=C3N=C1)O)[H])=C(C)\C([C@H](C/1(C)C)CCC(N)=O)=N\C\1=C/C([C@H]([C@@]\1(CC(N)=O)C)CCC(N)=O)=N/C/1=C(C)\C1=N[C@]2(C)[C@@](C)(CC(N)=O)[C@@H]1CCC(N)=O ZIHHMGTYZOSFRC-UWWAPWIJSA-M 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 210000003405 ileum Anatomy 0.000 description 2
- 244000000053 intestinal parasite Species 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 244000144972 livestock Species 0.000 description 2
- 238000009115 maintenance therapy Methods 0.000 description 2
- 230000036210 malignancy Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 235000007672 methylcobalamin Nutrition 0.000 description 2
- 239000011585 methylcobalamin Substances 0.000 description 2
- JEWJRMKHSMTXPP-BYFNXCQMSA-M methylcobalamin Chemical compound C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O JEWJRMKHSMTXPP-BYFNXCQMSA-M 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- 201000006417 multiple sclerosis Diseases 0.000 description 2
- 229940100652 nasal gel Drugs 0.000 description 2
- 230000009826 neoplastic cell growth Effects 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 210000001711 oxyntic cell Anatomy 0.000 description 2
- 239000003186 pharmaceutical solution Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 2
- 238000000275 quality assurance Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 235000019515 salmon Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000012430 stability testing Methods 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000001839 systemic circulation Effects 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 210000001944 turbinate Anatomy 0.000 description 2
- 210000005166 vasculature Anatomy 0.000 description 2
- 229940004543 vitamin b 12 nasal spray Drugs 0.000 description 2
- 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 1
- 208000002310 Achlorhydria Diseases 0.000 description 1
- 201000009487 Amblyopia Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 206010002065 Anaemia megaloblastic Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 208000000412 Avitaminosis Diseases 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 240000000560 Citrus x paradisi Species 0.000 description 1
- 102100036486 Cobalamin binding intrinsic factor Human genes 0.000 description 1
- 101710123904 Cobalamin binding intrinsic factor Proteins 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 208000016192 Demyelinating disease Diseases 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000029462 Immunodeficiency disease Diseases 0.000 description 1
- 206010022971 Iron Deficiencies Diseases 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 208000000682 Megaloblastic Anemia Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 206010029306 Neurological signs and symptoms Diseases 0.000 description 1
- 241000208125 Nicotiana Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 206010061323 Optic neuropathy Diseases 0.000 description 1
- 208000012868 Overgrowth Diseases 0.000 description 1
- 208000016222 Pancreatic disease Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- 206010047627 Vitamin deficiencies Diseases 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- 235000013361 beverage Nutrition 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 102000023732 binding proteins Human genes 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 230000003822 cell turnover Effects 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 210000004081 cilia Anatomy 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 231100001010 corrosive Toxicity 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 210000005224 forefinger Anatomy 0.000 description 1
- 238000013110 gastrectomy Methods 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 210000005095 gastrointestinal system Anatomy 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 210000004247 hand Anatomy 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 210000000777 hematopoietic system Anatomy 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000009326 ileitis Diseases 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000013160 medical therapy Methods 0.000 description 1
- 231100001016 megaloblastic anemia Toxicity 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229940111688 monobasic potassium phosphate Drugs 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 230000008450 motivation Effects 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 230000016273 neuron death Effects 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000003300 oropharynx Anatomy 0.000 description 1
- 208000035824 paresthesia Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- IWZKICVEHNUQTL-UHFFFAOYSA-M potassium hydrogen phthalate Chemical compound [K+].OC(=O)C1=CC=CC=C1C([O-])=O IWZKICVEHNUQTL-UHFFFAOYSA-M 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229960000999 sodium citrate dihydrate Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 208000005057 thyrotoxicosis Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 206010044697 tropical sprue Diseases 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 229940115535 vitamin b 12 nasal gel Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 229940072358 xylocaine Drugs 0.000 description 1
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
- A61K9/08—Solutions
-
- 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
- A61K9/0043—Nose
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7135—Compounds containing heavy metals
- A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
-
- 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
-
- 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
- A61P7/06—Antianaemics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Otolaryngology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Hematology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2863377A CA2863377C (en) | 2006-06-23 | 2006-06-23 | Cyanocobalamin low viscosity aqueous formulations for intranasal delivery |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2006/024685 WO2007149098A1 (en) | 2006-06-23 | 2006-06-23 | Cyanocobalamin low viscosity aqueous formulations for intranasal delivery |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2863377A Division CA2863377C (en) | 2006-06-23 | 2006-06-23 | Cyanocobalamin low viscosity aqueous formulations for intranasal delivery |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2656823A1 CA2656823A1 (en) | 2007-12-27 |
| CA2656823C true CA2656823C (en) | 2015-02-03 |
Family
ID=38833714
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2656823A Expired - Fee Related CA2656823C (en) | 2006-06-23 | 2006-06-23 | Cyanocobalamin low viscosity aqueous formulations for intranasal delivery |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP2035441A4 (ko) |
| JP (1) | JP5769924B2 (ko) |
| KR (3) | KR20170098977A (ko) |
| CN (1) | CN101600729A (ko) |
| AU (1) | AU2006344733B2 (ko) |
| CA (1) | CA2656823C (ko) |
| IL (2) | IL196038A (ko) |
| NO (1) | NO20090368L (ko) |
| WO (1) | WO2007149098A1 (ko) |
| ZA (1) | ZA200900191B (ko) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2632430T3 (en) * | 2010-10-29 | 2018-09-17 | Troikaa Pharmaceuticals Ltd | : NASAL COMPOSITIONS OF B12 VITAMIN |
| CN110603033A (zh) * | 2017-03-02 | 2019-12-20 | 荷兰可再生能源公司 | 生理活性物质的鼻内给药 |
| US20220111162A1 (en) * | 2020-07-29 | 2022-04-14 | Lido Ventures Llc | Apparatus, system, and method for facilitating intranasal treatment of a patient |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3682862D1 (de) * | 1985-04-16 | 1992-01-23 | Nastech Pharm Co | Aerosolmittel zur nasenverstaeubung von vitamin b 12. |
| US4724231A (en) * | 1985-04-16 | 1988-02-09 | Nastech Pharmaceutical, Inc. | Nasel compositions containing vitamin B12 |
| US5112804A (en) * | 1987-04-01 | 1992-05-12 | Temple University Of The Commonwealth System Of Higher Education | Pharmaceutical composition and method of intranasal administration |
| US4959176A (en) * | 1988-04-29 | 1990-09-25 | Beckman Instruments, Inc. | High resolution non corrosive amino acid analysis buffer solutions |
| US5227311A (en) * | 1988-10-11 | 1993-07-13 | Abbott Laboratories | Intrinsic factor to determine B12 |
| BE1007839A6 (nl) * | 1993-12-20 | 1995-10-31 | Merkus Franciscus W H M Prof | Farmaceutische compositie voor de nasale toediening van hydroxocobalamine. |
| US6406730B1 (en) * | 1998-12-01 | 2002-06-18 | Carl E. Banyard | Process for producing low acid food products |
| FR2787029A1 (fr) * | 1998-12-09 | 2000-06-16 | Biovector Therapeutics | Utilisation dans une composition pharmaceutique pour l'administration par voie nasale de vitamine b12 pour la delivrance d'agents actifs au systeme nerveux central |
| PT1320356E (pt) * | 2000-09-20 | 2008-01-03 | Nycomed Pharma As | Preparação de emulsões e concentrados destas |
| US20060074034A1 (en) * | 2001-09-17 | 2006-04-06 | Collins Douglas A | Cobalamin mediated delivery of nucleic acids, analogs and derivatives thereof |
| US6911434B2 (en) * | 2002-02-04 | 2005-06-28 | Corixa Corporation | Prophylactic and therapeutic treatment of infectious and other diseases with immunoeffector compounds |
| US20040109826A1 (en) * | 2002-12-06 | 2004-06-10 | Dey, L.P. | Stabilized albuterol compositions and method of preparation thereof |
| DE10300719A1 (de) * | 2003-01-11 | 2004-07-22 | Basf Ag | Verbessertes Verfahren zur Herstellung von Vitamin B12 |
| US20060127320A1 (en) * | 2004-05-10 | 2006-06-15 | Nastech Pharmaceutical Company Inc. | Method of delivering parathyroid hormone to a human |
| US20060046969A1 (en) * | 2004-08-25 | 2006-03-02 | Aegis Therapeutics Llc | Antibacterial compositions for drug administration |
| JP2009504767A (ja) * | 2005-08-17 | 2009-02-05 | フレミング・アンド・カンパニー・ファーマシューティカルズ | ビタミンｂ１２鼻用スプレーおよび使用方法 |
-
2006
- 2006-06-23 JP JP2009516468A patent/JP5769924B2/ja not_active Expired - Fee Related
- 2006-06-23 KR KR1020177023153A patent/KR20170098977A/ko not_active Application Discontinuation
- 2006-06-23 CA CA2656823A patent/CA2656823C/en not_active Expired - Fee Related
- 2006-06-23 EP EP06785533A patent/EP2035441A4/en not_active Ceased
- 2006-06-23 AU AU2006344733A patent/AU2006344733B2/en not_active Ceased
- 2006-06-23 KR KR1020097001414A patent/KR20090074722A/ko not_active Application Discontinuation
- 2006-06-23 KR KR1020147021098A patent/KR20140101010A/ko not_active Application Discontinuation
- 2006-06-23 WO PCT/US2006/024685 patent/WO2007149098A1/en active Application Filing
- 2006-06-23 CN CNA2006800556586A patent/CN101600729A/zh active Pending
-
2008
- 2008-12-18 IL IL196038A patent/IL196038A/en active IP Right Grant
-
2009
- 2009-01-09 ZA ZA2009/00191A patent/ZA200900191B/en unknown
- 2009-01-23 NO NO20090368A patent/NO20090368L/no not_active Application Discontinuation
-
2016
- 2016-10-21 IL IL248447A patent/IL248447B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP2035441A4 (en) | 2013-01-16 |
| JP2009541312A (ja) | 2009-11-26 |
| AU2006344733A1 (en) | 2007-12-27 |
| NO20090368L (no) | 2009-03-23 |
| IL196038A0 (en) | 2009-09-01 |
| KR20140101010A (ko) | 2014-08-18 |
| AU2006344733B2 (en) | 2014-02-27 |
| IL248447A0 (en) | 2016-11-30 |
| IL248447B (en) | 2021-10-31 |
| KR20170098977A (ko) | 2017-08-30 |
| WO2007149098A1 (en) | 2007-12-27 |
| JP5769924B2 (ja) | 2015-08-26 |
| KR20090074722A (ko) | 2009-07-07 |
| EP2035441A1 (en) | 2009-03-18 |
| ZA200900191B (en) | 2012-09-26 |
| IL196038A (en) | 2016-10-31 |
| CA2656823A1 (en) | 2007-12-27 |
| CN101600729A (zh) | 2009-12-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20190216842A1 (en) | Vitamin b12 nasal spray and method of use | |
| EP3679941B1 (en) | Safe desmopressin administration | |
| US9415007B2 (en) | Cyanocobalamin low viscosity aqueous formulations for intranasal delivery | |
| KR20220167279A (ko) | 알코올 사용 장애의 치료용 조성물, 장치 및 방법 | |
| CA2656823C (en) | Cyanocobalamin low viscosity aqueous formulations for intranasal delivery | |
| US20200390691A1 (en) | Compositions, devices, and methods for the treatment of overdose and reward-based disorders | |
| US7229636B1 (en) | Cyanocobalamin low viscosity aqueous formulations for intranasal delivery | |
| AU2014202415B2 (en) | Cyanocobalamin low viscosity aqueous formulations for intranasal delivery | |
| CA2863377C (en) | Cyanocobalamin low viscosity aqueous formulations for intranasal delivery | |
| JP6097787B2 (ja) | 鼻内送達用シアノコバラミン低粘度水性製剤 | |
| JP5797227B2 (ja) | 鼻内送達用シアノコバラミン低粘度水性製剤 | |
| CA3124202A1 (en) | Compositions, devices, and methods for the treatment of overdose and reward-based disorders | |
| Feller et al. | Vitamin B 12 nasal spray and method of use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20220623 |