CN109922805A - 液体纳洛酮喷雾 - Google Patents
液体纳洛酮喷雾 Download PDFInfo
- Publication number
- CN109922805A CN109922805A CN201780063967.6A CN201780063967A CN109922805A CN 109922805 A CN109922805 A CN 109922805A CN 201780063967 A CN201780063967 A CN 201780063967A CN 109922805 A CN109922805 A CN 109922805A
- Authority
- CN
- China
- Prior art keywords
- preparation
- naloxone
- spray formulation
- liquid spray
- preferred
- 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.)
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- 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 141
- 229960004127 naloxone Drugs 0.000 title claims abstract description 137
- 239000007788 liquid Substances 0.000 title claims abstract description 103
- 238000005507 spraying Methods 0.000 title description 36
- 238000002360 preparation method Methods 0.000 claims abstract description 270
- 150000003839 salts Chemical class 0.000 claims abstract description 40
- 239000007921 spray Substances 0.000 claims description 160
- 239000000203 mixture Substances 0.000 claims description 152
- 238000009472 formulation Methods 0.000 claims description 130
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 105
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 99
- 235000019441 ethanol Nutrition 0.000 claims description 65
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 47
- 239000006184 cosolvent Substances 0.000 claims description 40
- 239000002738 chelating agent Substances 0.000 claims description 39
- 229960004756 ethanol Drugs 0.000 claims description 36
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 32
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 32
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 18
- 239000003963 antioxidant agent Substances 0.000 claims description 18
- 230000003078 antioxidant effect Effects 0.000 claims description 18
- 235000006708 antioxidants Nutrition 0.000 claims description 18
- 239000007951 isotonicity adjuster Substances 0.000 claims description 18
- 239000000872 buffer Substances 0.000 claims description 17
- 235000010378 sodium ascorbate Nutrition 0.000 claims description 17
- 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 17
- 229960005055 sodium ascorbate Drugs 0.000 claims description 17
- 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 17
- 239000003795 chemical substances by application Substances 0.000 claims description 16
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 12
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 6
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 6
- 239000011780 sodium chloride Substances 0.000 claims description 6
- XMEKHKCRNHDFOW-UHFFFAOYSA-N O.O.[Na].[Na] Chemical compound O.O.[Na].[Na] XMEKHKCRNHDFOW-UHFFFAOYSA-N 0.000 claims description 3
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical group [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 1
- 230000008058 pain sensation Effects 0.000 abstract description 9
- 208000008017 Hypohidrosis Diseases 0.000 abstract description 8
- 206010002512 anhidrosis Diseases 0.000 abstract description 8
- 230000037001 anhydrosis Effects 0.000 abstract description 8
- 238000000034 method Methods 0.000 abstract description 8
- 229940124636 opioid drug Drugs 0.000 abstract description 7
- 206010010356 Congenital anomaly Diseases 0.000 abstract description 6
- 239000012535 impurity Substances 0.000 description 84
- OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound 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 description 38
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 34
- 239000003623 enhancer Substances 0.000 description 33
- 230000035515 penetration Effects 0.000 description 30
- 239000000796 flavoring agent Substances 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 19
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 19
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 19
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 19
- 239000003755 preservative agent Substances 0.000 description 19
- 230000002335 preservative effect Effects 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 18
- 235000013355 food flavoring agent Nutrition 0.000 description 18
- 238000012360 testing method Methods 0.000 description 18
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 17
- 229960002446 octanoic acid Drugs 0.000 description 17
- 238000009826 distribution Methods 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 210000001331 nose Anatomy 0.000 description 15
- 229940071106 ethylenediaminetetraacetate Drugs 0.000 description 14
- 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 12
- 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 12
- 235000003599 food sweetener Nutrition 0.000 description 12
- 239000003765 sweetening agent Substances 0.000 description 12
- 229940041616 menthol Drugs 0.000 description 11
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 11
- 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 10
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 10
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 229910052708 sodium Inorganic materials 0.000 description 10
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 9
- 235000019345 sodium thiosulphate Nutrition 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- -1 hydroxyl Methyl Chemical group 0.000 description 8
- 230000036961 partial effect Effects 0.000 description 8
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 7
- 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 7
- 239000002253 acid Substances 0.000 description 7
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 7
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 7
- 230000036470 plasma concentration Effects 0.000 description 7
- 230000006641 stabilisation Effects 0.000 description 7
- 238000011105 stabilization Methods 0.000 description 7
- 239000003002 pH adjusting agent Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 229960004217 benzyl alcohol Drugs 0.000 description 5
- 229960001484 edetic acid Drugs 0.000 description 5
- 235000011187 glycerol Nutrition 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- 229920000136 polysorbate Polymers 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 238000012935 Averaging Methods 0.000 description 4
- 241000220223 Fragaria Species 0.000 description 4
- 235000016623 Fragaria vesca Nutrition 0.000 description 4
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 239000004376 Sucralose Substances 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
- 235000010323 ascorbic acid Nutrition 0.000 description 4
- 239000011668 ascorbic acid Substances 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
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-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
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 4
- 239000007922 nasal spray Substances 0.000 description 4
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 4
- 235000019477 peppermint oil Nutrition 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
- 238000013112 stability test Methods 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- 235000019408 sucralose Nutrition 0.000 description 4
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound 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 4
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 3
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- RCEAADKTGXTDOA-UHFFFAOYSA-N OS(O)(=O)=O.CCCCCCCCCCCC[Na] Chemical compound OS(O)(=O)=O.CCCCCCCCCCCC[Na] RCEAADKTGXTDOA-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
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- 229960001927 cetylpyridinium chloride Drugs 0.000 description 3
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
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- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
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- 229920000053 polysorbate 80 Polymers 0.000 description 3
- WZWGGYFEOBVNLA-UHFFFAOYSA-N sodium;dihydrate Chemical compound O.O.[Na] WZWGGYFEOBVNLA-UHFFFAOYSA-N 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
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- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- BYKRNSHANADUFY-UHFFFAOYSA-M sodium octanoate Chemical compound [Na+].CCCCCCCC([O-])=O BYKRNSHANADUFY-UHFFFAOYSA-M 0.000 description 1
- 229940001482 sodium sulfite Drugs 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 229940053209 suboxone Drugs 0.000 description 1
- 210000004243 sweat Anatomy 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
- 229960000984 tocofersolan Drugs 0.000 description 1
- 229950004288 tosilate Drugs 0.000 description 1
- 238000012546 transfer Methods 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
- 239000002076 α-tocopherol Substances 0.000 description 1
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- 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
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- A—HUMAN NECESSITIES
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- 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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- 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
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- 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
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- A—HUMAN NECESSITIES
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- 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
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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
- A61K9/08—Solutions
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
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- Animal Behavior & Ethology (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Emergency Medicine (AREA)
- Otolaryngology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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US15/238,909 US10722510B2 (en) | 2014-07-08 | 2016-08-17 | Liquid naloxone spray |
US15/238,909 | 2016-08-17 | ||
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 |
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CN109922805A true CN109922805A (zh) | 2019-06-21 |
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CN201780063967.6A Pending CN109922805A (zh) | 2016-08-17 | 2017-08-10 | 液体纳洛酮喷雾 |
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EP (1) | EP3500261A4 (enrdf_load_stackoverflow) |
JP (2) | JP7114570B2 (enrdf_load_stackoverflow) |
CN (1) | CN109922805A (enrdf_load_stackoverflow) |
AU (1) | AU2017312811B2 (enrdf_load_stackoverflow) |
CA (1) | CA3033897C (enrdf_load_stackoverflow) |
MA (1) | MA45995A (enrdf_load_stackoverflow) |
WO (1) | WO2018034920A1 (enrdf_load_stackoverflow) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112138250A (zh) * | 2019-06-28 | 2020-12-29 | 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 |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8580801B2 (en) | 2008-07-23 | 2013-11-12 | Robert I. Henkin | Phosphodiesterase inhibitor treatment |
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 |
WO2018034920A1 (en) * | 2016-08-17 | 2018-02-22 | Insys Development Company, Inc. | Liquid naloxone spray |
US20180193332A1 (en) * | 2017-10-09 | 2018-07-12 | Adapt Pharma Operations Limited | Low-temperature stable opioid antagonist solutions |
MX2021007213A (es) * | 2018-12-19 | 2021-09-23 | Grace therapeutics Inc | Composicion terapeutica de lidocaina intranasal. |
WO2020172498A1 (en) * | 2019-02-21 | 2020-08-27 | Pharmaceutical Productions, Inc. | Naloxone formulations for sublingual and/or buccal administration |
AU2021217164A1 (en) * | 2020-02-05 | 2022-08-25 | Summit Biosciences Inc. | Drug products for intranasal administration and uses thereof |
EP4460291A1 (en) * | 2022-01-06 | 2024-11-13 | Cyrano Therapeutics, Inc. | Improved nasal administration of parkinson's therapeutics |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103764119A (zh) * | 2011-05-13 | 2014-04-30 | 欧洲凯尔特公司 | 包含纳洛酮的鼻内药物剂型 |
US20160008349A1 (en) * | 2014-07-08 | 2016-01-14 | Insys Pharma, Inc. | Sublingual naloxone spray |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
PT2706986E (pt) * | 2011-09-19 | 2015-07-07 | Orexo Ab | Nova composição farmacêutica resistente ao abuso para o tratamento da dependência de opiáceos |
WO2014018098A1 (en) | 2012-07-26 | 2014-01-30 | DePuy Synthes Products, LLC | Expandable implant |
CA2795324C (en) * | 2012-11-09 | 2015-07-14 | Purdue Pharma | Pharmaceutical compositions comprising hydromorphone and naloxone |
JP2016529328A (ja) | 2013-09-10 | 2016-09-23 | インシス・ファーマ・インコーポレーテッド | 舌下ブプレノルフィンスプレー |
CN103637987B (zh) | 2013-12-09 | 2015-12-02 | 韩彬 | 羟考酮的液体药物组合物 |
EP3082816B1 (en) | 2013-12-20 | 2019-03-20 | Indivior UK Limited | Intranasal naloxone compositions and methods of making and using same |
US9211253B2 (en) | 2014-03-14 | 2015-12-15 | Lightlake Therapeutics 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 |
WO2018034920A1 (en) | 2016-08-17 | 2018-02-22 | Insys Development Company, Inc. | Liquid naloxone spray |
-
2017
- 2017-08-10 WO PCT/US2017/046198 patent/WO2018034920A1/en unknown
- 2017-08-10 CN CN201780063967.6A patent/CN109922805A/zh active Pending
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2022
- 2022-05-18 JP JP2022081328A patent/JP7455157B2/ja active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103764119A (zh) * | 2011-05-13 | 2014-04-30 | 欧洲凯尔特公司 | 包含纳洛酮的鼻内药物剂型 |
US20160008349A1 (en) * | 2014-07-08 | 2016-01-14 | Insys Pharma, Inc. | Sublingual naloxone spray |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112138250A (zh) * | 2019-06-28 | 2020-12-29 | 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 |
CN112138250B (zh) * | 2019-06-28 | 2023-04-14 | 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 |
Also Published As
Publication number | Publication date |
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AU2017312811A1 (en) | 2019-03-07 |
MA45995A (fr) | 2019-06-26 |
EP3500261A4 (en) | 2020-05-06 |
CA3033897A1 (en) | 2018-02-22 |
JP7114570B2 (ja) | 2022-08-08 |
JP2022119843A (ja) | 2022-08-17 |
CA3033897C (en) | 2024-03-26 |
EP3500261A1 (en) | 2019-06-26 |
AU2017312811B2 (en) | 2023-03-16 |
WO2018034920A1 (en) | 2018-02-22 |
JP2019528278A (ja) | 2019-10-10 |
JP7455157B2 (ja) | 2024-03-25 |
AU2017312811A8 (en) | 2019-03-14 |
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