CA3033897C - Liquid naloxone spray - Google Patents

Liquid naloxone spray Download PDF

Info

Publication number: CA3033897C
Authority: CA; Canada
Prior art keywords: formulation; formulations; impurity; naloxone; spray
Prior art date: 2016-08-17
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.): Active

Application number

CA3033897A

Other languages

English (en)

French (fr)

Other versions

CA3033897A1 (en

Inventor

Kiran AMANCHA

Shivani CHILAMPALLI

Thrimoorthy Potta

Ningxin YAN

Venkat R. Goskonda

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Hikma Pharmaceuticals USA Inc

Original Assignee

Hikma Pharmaceuticals USA Inc

Priority date (The priority date 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 date listed.)

2016-08-17

Filing date

2017-08-10

Publication date

2024-03-26

2016-08-17 Priority claimed from US15/238,909 external-priority patent/US10722510B2/en

2017-05-22 Priority claimed from US15/601,331 external-priority patent/US10617686B2/en

2017-08-10 Application filed by Hikma Pharmaceuticals USA Inc filed Critical Hikma Pharmaceuticals USA Inc

2018-02-22 Publication of CA3033897A1 publication Critical patent/CA3033897A1/en

2024-03-26 Application granted granted Critical

2024-03-26 Publication of CA3033897C publication Critical patent/CA3033897C/en

Status Active legal-status Critical Current

2037-08-10 Anticipated expiration legal-status Critical

Links

UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 title claims abstract description 180
229960004127 naloxone Drugs 0.000 title claims abstract description 170
239000007921 spray Substances 0.000 title claims description 180
239000007788 liquid Substances 0.000 title claims description 89
239000000203 mixture Substances 0.000 claims abstract description 401
238000009472 formulation Methods 0.000 claims abstract description 391
150000003839 salts Chemical class 0.000 claims abstract description 41
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 115
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 100
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 57
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 52
OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical group O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 claims description 44
239000002738 chelating agent Substances 0.000 claims description 40
229960000686 benzalkonium chloride Drugs 0.000 claims description 34
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 34
239000003795 chemical substances by application Substances 0.000 claims description 20
239000003963 antioxidant agent Substances 0.000 claims description 19
235000006708 antioxidants Nutrition 0.000 claims description 19
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 16
230000003078 antioxidant effect Effects 0.000 claims description 16
235000010378 sodium ascorbate Nutrition 0.000 claims description 13
PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 claims description 13
229960005055 sodium ascorbate Drugs 0.000 claims description 13
PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical group [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 claims description 12
239000007922 nasal spray Substances 0.000 claims description 9
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 8
229940097496 nasal spray Drugs 0.000 claims description 8
239000011780 sodium chloride Substances 0.000 claims description 8
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical class IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 3
WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 2
238000000034 method Methods 0.000 abstract description 10
208000026251 Opioid-Related disease Diseases 0.000 abstract description 9
201000005040 opiate dependence Diseases 0.000 abstract description 9
208000012488 Opiate Overdose Diseases 0.000 abstract description 8
239000012669 liquid formulation Substances 0.000 abstract description 8
208000017359 Hereditary sensory and autonomic neuropathy type 4 Diseases 0.000 abstract description 6
208000037584 hereditary sensory and autonomic neuropathy Diseases 0.000 abstract description 6
239000012535 impurity Substances 0.000 description 211
WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 40
239000006184 cosolvent Substances 0.000 description 35
XUKUURHRXDUEBC-SXOMAYOGSA-N (3s,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SXOMAYOGSA-N 0.000 description 33
AAEQXEDPVFIFDK-UHFFFAOYSA-N 3-(4-fluorobenzoyl)-2-(2-methylpropanoyl)-n,3-diphenyloxirane-2-carboxamide Chemical compound C=1C=CC=CC=1NC(=O)C1(C(=O)C(C)C)OC1(C=1C=CC=CC=1)C(=O)C1=CC=C(F)C=C1 AAEQXEDPVFIFDK-UHFFFAOYSA-N 0.000 description 33
229960004756 ethanol Drugs 0.000 description 31
238000003556 assay Methods 0.000 description 29
239000003961 penetration enhancing agent Substances 0.000 description 28
239000000796 flavoring agent Substances 0.000 description 27
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 27
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 22
NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 21
235000013355 food flavoring agent Nutrition 0.000 description 21
239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 20
229960002446 octanoic acid Drugs 0.000 description 20
239000002245 particle Substances 0.000 description 20
239000003755 preservative agent Substances 0.000 description 19
230000002335 preservative effect Effects 0.000 description 19
238000012360 testing method Methods 0.000 description 19
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 14
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 14
229960002216 methylparaben Drugs 0.000 description 14
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 13
229960001484 edetic acid Drugs 0.000 description 13
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 12
235000003599 food sweetener Nutrition 0.000 description 12
239000003765 sweetening agent Substances 0.000 description 12
NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 11
238000004458 analytical method Methods 0.000 description 11
235000010323 ascorbic acid Nutrition 0.000 description 11
239000011668 ascorbic acid Substances 0.000 description 11
229940041616 menthol Drugs 0.000 description 11
229940072107 ascorbate Drugs 0.000 description 10
239000000243 solution Substances 0.000 description 10
239000002904 solvent Substances 0.000 description 10
239000004322 Butylated hydroxytoluene Substances 0.000 description 8
NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 8
241000220223 Fragaria Species 0.000 description 8
235000016623 Fragaria vesca Nutrition 0.000 description 8
235000011363 Fragaria x ananassa Nutrition 0.000 description 8
235000019282 butylated hydroxyanisole Nutrition 0.000 description 8
235000010354 butylated hydroxytoluene Nutrition 0.000 description 8
229940095259 butylated hydroxytoluene Drugs 0.000 description 8
239000004255 Butylated hydroxyanisole Substances 0.000 description 7
239000004376 Sucralose Substances 0.000 description 7
229940043253 butylated hydroxyanisole Drugs 0.000 description 7
CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 7
230000036470 plasma concentration Effects 0.000 description 7
238000012430 stability testing Methods 0.000 description 7
235000019408 sucralose Nutrition 0.000 description 7
BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical group O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 7
VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 6
ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 6
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 6
235000019634 flavors Nutrition 0.000 description 6
229940053685 naloxone nasal spray Drugs 0.000 description 6
239000003002 pH adjusting agent Substances 0.000 description 6
239000011734 sodium Substances 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 6
229940001474 sodium thiosulfate Drugs 0.000 description 6
235000019345 sodium thiosulphate Nutrition 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
239000003623 enhancer Substances 0.000 description 5
235000011187 glycerol Nutrition 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
238000011282 treatment Methods 0.000 description 5
TXMZWEASFRBVKY-IOQDSZRYSA-N (4r,4as,7ar,12bs)-4a,9-dihydroxy-3-prop-2-enyl-2,4,5,6,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one;dihydrate;hydrochloride Chemical compound O.O.Cl.O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C TXMZWEASFRBVKY-IOQDSZRYSA-N 0.000 description 4
RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 description 4
QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 4
YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 4
235000019445 benzyl alcohol Nutrition 0.000 description 4
229960004217 benzyl alcohol Drugs 0.000 description 4
ULDHMXUKGWMISQ-UHFFFAOYSA-N carvone Chemical compound CC(=C)C1CC=C(C)C(=O)C1 ULDHMXUKGWMISQ-UHFFFAOYSA-N 0.000 description 4
GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 4
150000004683 dihydrates Chemical class 0.000 description 4
POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 4
239000001525 mentha piperita l. herb oil Substances 0.000 description 4
235000019477 peppermint oil Nutrition 0.000 description 4
229920000136 polysorbate Polymers 0.000 description 4
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
239000008213 purified water Substances 0.000 description 4
DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
208000008017 Hypohidrosis Diseases 0.000 description 3
VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
ILRKKHJEINIICQ-OOFFSTKBSA-N Monoammonium glycyrrhizinate Chemical compound N.O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O ILRKKHJEINIICQ-OOFFSTKBSA-N 0.000 description 3
229910019142 PO4 Inorganic materials 0.000 description 3
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 3
PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 description 3
VLSOAXRVHARBEQ-UHFFFAOYSA-N [4-fluoro-2-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=C(F)C=C1CO VLSOAXRVHARBEQ-UHFFFAOYSA-N 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
206010002512 anhidrosis Diseases 0.000 description 3
230000037001 anhydrosis Effects 0.000 description 3
RMRJXGBAOAMLHD-CTAPUXPBSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-CTAPUXPBSA-N 0.000 description 3
GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000003814 drug Substances 0.000 description 3
229940009662 edetate Drugs 0.000 description 3
229940124274 edetate disodium Drugs 0.000 description 3
-1 glucaronate Chemical compound 0.000 description 3
229940075507 glyceryl monostearate Drugs 0.000 description 3
LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 3
239000001685 glycyrrhizic acid Substances 0.000 description 3
229960004949 glycyrrhizic acid Drugs 0.000 description 3
UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 3
235000019410 glycyrrhizin Nutrition 0.000 description 3
LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
238000007918 intramuscular administration Methods 0.000 description 3
244000309715 mini pig Species 0.000 description 3
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 3
229940065778 narcan Drugs 0.000 description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
239000010452 phosphate Substances 0.000 description 3
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
229920000053 polysorbate 80 Polymers 0.000 description 3
229940068965 polysorbates Drugs 0.000 description 3
FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 3
OABYVIYXWMZFFJ-ZUHYDKSRSA-M sodium glycocholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 OABYVIYXWMZFFJ-ZUHYDKSRSA-M 0.000 description 3
235000019333 sodium laurylsulphate Nutrition 0.000 description 3
229940053209 suboxone Drugs 0.000 description 3
239000000126 substance Substances 0.000 description 3
WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
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238000011084 recovery Methods 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
229940083542 sodium Drugs 0.000 description 1
229960002668 sodium chloride Drugs 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
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 1
229960001790 sodium citrate Drugs 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
229940001482 sodium sulfite Drugs 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
WZWGGYFEOBVNLA-UHFFFAOYSA-N sodium;dihydrate Chemical compound O.O.[Na] WZWGGYFEOBVNLA-UHFFFAOYSA-N 0.000 description 1
NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
FQXXSQDCDRQNQE-VMDGZTHMSA-N thebaine Chemical compound C([C@@H](N(CC1)C)C2=CC=C3OC)C4=CC=C(OC)C5=C4[C@@]21[C@H]3O5 FQXXSQDCDRQNQE-VMDGZTHMSA-N 0.000 description 1
229930003945 thebaine Natural products 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
238000005303 weighing Methods 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
- A61K31/33—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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
- 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
- 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
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Epidemiology (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Oil, Petroleum & Natural Gas (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Emergency Medicine (AREA)
Otolaryngology (AREA)
Medicinal Preparation (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA3033897A 2016-08-17 2017-08-10 Liquid naloxone spray Active CA3033897C (en)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US15/238,909		2016-08-17
US15/238,909 US10722510B2 (en)	2014-07-08	2016-08-17	Liquid naloxone spray
US15/601,331 US10617686B2 (en)	2014-07-08	2017-05-22	Liquid naloxone spray
US15/601,331		2017-05-22
PCT/US2017/046198 WO2018034920A1 (en)	2016-08-17	2017-08-10	Liquid naloxone spray

Publications (2)

Publication Number	Publication Date
CA3033897A1 CA3033897A1 (en)	2018-02-22
CA3033897C true CA3033897C (en)	2024-03-26

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ID=61197156

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA3033897A Active CA3033897C (en)	2016-08-17	2017-08-10	Liquid naloxone spray

Country Status (7)

Country	Link
EP (1)	EP3500261A4 (zh)
JP (2)	JP7114570B2 (zh)
CN (1)	CN109922805A (zh)
AU (1)	AU2017312811B2 (zh)
CA (1)	CA3033897C (zh)
MA (1)	MA45995A (zh)
WO (1)	WO2018034920A1 (zh)

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WO2015126944A1 (en)	2014-02-18	2015-08-27	Henkin Robert I	Methods and compositions for diagnosing and treating loss and/or distortion of taste or smell
JP7114570B2 (ja) *	2016-08-17	2022-08-08	ヒクマ・ファーマシューティカルズ・ユー・エス・エイ・インコーポレイテッド	液体ナロキソンスプレー
US20180193332A1 (en) *	2017-10-09	2018-07-12	Adapt Pharma Operations Limited	Low-temperature stable opioid antagonist solutions
EP3927321A1 (en) *	2019-02-21	2021-12-29	Pharmaceutical Productions, Inc.	Naloxone formulations for sublingual and/or buccal administration
CN116474219A (zh) *	2019-06-28	2023-07-25	四川普锐特药业有限公司	保持给药均一度的药物流体分配器及右美托咪定鼻喷器
CA3166250A1 (en) *	2020-02-05	2021-08-12	Gregory G. Plucinski	Drug products for intranasal administration and uses thereof
KR20240134157A (ko) *	2022-01-06	2024-09-06	시라노 테라퓨틱스, 아이엔씨.	파킨슨 치료제의 개선된 코 투여

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US14730A (en)		1856-04-22		Improvement in corn-harvesters
US585A (en)		1838-01-27		Apparatus for extinguishing sparks in the chimneys oe steam-boilers
CN1575795A (zh)	2003-06-25	2005-02-09	中国人民解放军军事医学科学院毒物药物研究所	盐酸纳洛酮鼻腔喷雾剂
US8627816B2 (en) *	2011-02-28	2014-01-14	Intelliject, Inc.	Medicament delivery device for administration of opioid antagonists including formulations for naloxone
AU2012257785B2 (en) *	2011-05-13	2016-04-14	Euro-Celtique S.A.	Intranasal pharmaceutical dosage forms comprising naloxone
DK2706986T3 (en) *	2011-09-19	2015-06-01	Orexo Ab	NEW ADDICTION PREVENTING PHARMACEUTICAL COMPOSITION FOR TREATMENT OF OPIOID ADDICTION
WO2014018098A1 (en)	2012-07-26	2014-01-30	DePuy Synthes Products, LLC	Expandable implant
CA2881144A1 (en) *	2012-11-09	2014-05-09	Purdue Pharma	Pharmaceutical compositions comprising hydromorphone and naloxone
DK3043777T3 (da) *	2013-09-10	2020-07-20	Fresh Cut Dev Llc	Sublingual buprenorphinspray
CN103637987B (zh) *	2013-12-09	2015-12-02	韩彬	羟考酮的液体药物组合物
WO2015095644A1 (en)	2013-12-20	2015-06-25	AntiOP, Inc.	Intranasal naloxone compositions and methods of making and using same
SG10202003562WA (en)	2014-03-14	2020-05-28	Opiant Pharmaceuticals Inc	Nasal drug products and methods of their use
US9480644B2 (en)	2014-03-14	2016-11-01	Opiant Pharmaceuticals, Inc.	Nasal drug products and methods of their use
US20160199294A1 (en) *	2014-07-08	2016-07-14	Insys Development Company, Inc.	Sublingual naloxone spray
WO2016007245A1 (en) *	2014-07-08	2016-01-14	Insys Pharma, Inc.	Sublingual naloxone spray
JP7114570B2 (ja)	2016-08-17	2022-08-08	ヒクマ・ファーマシューティカルズ・ユー・エス・エイ・インコーポレイテッド	液体ナロキソンスプレー

2017
- 2017-08-10 JP JP2019508941A patent/JP7114570B2/ja active Active
- 2017-08-10 WO PCT/US2017/046198 patent/WO2018034920A1/en unknown
- 2017-08-10 MA MA045995A patent/MA45995A/fr unknown
- 2017-08-10 AU AU2017312811A patent/AU2017312811B2/en active Active
- 2017-08-10 CA CA3033897A patent/CA3033897C/en active Active
- 2017-08-10 CN CN201780063967.6A patent/CN109922805A/zh active Pending
- 2017-08-10 EP EP17841883.6A patent/EP3500261A4/en active Pending
2022
- 2022-05-18 JP JP2022081328A patent/JP7455157B2/ja active Active

Also Published As

Publication number	Publication date
WO2018034920A1 (en)	2018-02-22
EP3500261A4 (en)	2020-05-06
JP7455157B2 (ja)	2024-03-25
AU2017312811A8 (en)	2019-03-14
JP2019528278A (ja)	2019-10-10
AU2017312811B2 (en)	2023-03-16
JP7114570B2 (ja)	2022-08-08
EP3500261A1 (en)	2019-06-26
CA3033897A1 (en)	2018-02-22
JP2022119843A (ja)	2022-08-17
AU2017312811A1 (en)	2019-03-07
CN109922805A (zh)	2019-06-21
MA45995A (fr)	2019-06-26

Publication	Publication Date	Title
CA3033897C (en)	2024-03-26	Liquid naloxone spray
US11628139B2 (en)	2023-04-18	Liquid naloxone spray
US10617686B2 (en)	2020-04-14	Liquid naloxone spray
US10441538B2 (en)	2019-10-15	Liquid naloxone spray
US9642848B2 (en)	2017-05-09	Sublingual naloxone spray
EP3043777B1 (en)	2020-04-22	Sublingual buprenorphine spray
US10722510B2 (en)	2020-07-28	Liquid naloxone spray
US20160199294A1 (en)	2016-07-14	Sublingual naloxone spray
EP3612173B1 (en)	2023-10-11	Epinephrine spray formulations
EP3277283B1 (en)	2021-03-03	Sildenafil sublingual spray formulations
US10973814B2 (en)	2021-04-13	Liquid naloxone spray
US9370518B2 (en)	2016-06-21	Sildenafil sublingual spray formulation
US20190224171A1 (en)	2019-07-25	Liquid rizatriptan compositions

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