SK282549B6 - Spôsob stabilizácie naloxonhydrochloridu - Google Patents

Spôsob stabilizácie naloxonhydrochloridu Download PDF

Info

Publication number: SK282549B6
Authority: SK; Slovakia
Prior art keywords: acid; derivatives; stabilizer; naloxone; salts
Prior art date: 1997-02-14

Application number

SK1092-99A

Other languages

English (en)

Slovak (sk)

Other versions

SK109299A3 (en

Inventor

Bernd Raffelsberger

Original Assignee

G�decke Aktiengesellschaft

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.)

1997-02-14

Filing date

1998-02-03

Publication date

2002-10-08

1998-02-03 Application filed by G�decke Aktiengesellschaft filed Critical G�decke Aktiengesellschaft

2000-08-14 Publication of SK109299A3 publication Critical patent/SK109299A3/sk

2002-10-08 Publication of SK282549B6 publication Critical patent/SK282549B6/sk

Links

238000000034 method Methods 0.000 title claims abstract description 13
230000006641 stabilisation Effects 0.000 title abstract description 3
238000011105 stabilization Methods 0.000 title abstract description 3
RGPDIGOSVORSAK-STHHAXOLSA-N naloxone hydrochloride Chemical compound Cl.O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C RGPDIGOSVORSAK-STHHAXOLSA-N 0.000 title description 42
229960005250 naloxone hydrochloride Drugs 0.000 title description 13
229960004127 naloxone Drugs 0.000 claims abstract description 35
150000003839 salts Chemical class 0.000 claims abstract description 25
RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims abstract description 22
239000003381 stabilizer Substances 0.000 claims abstract description 22
238000006471 dimerization reaction Methods 0.000 claims abstract description 17
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims abstract description 12
235000010269 sulphur dioxide Nutrition 0.000 claims abstract description 11
235000010265 sodium sulphite Nutrition 0.000 claims abstract description 6
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 claims abstract 8
239000000126 substance Substances 0.000 claims description 17
-1 PHB-esters Substances 0.000 claims description 16
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 13
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 12
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 12
239000002552 dosage form Substances 0.000 claims description 12
239000000203 mixture Substances 0.000 claims description 12
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 11
150000001875 compounds Chemical class 0.000 claims description 11
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 8
229910052751 metal Inorganic materials 0.000 claims description 8
239000002184 metal Substances 0.000 claims description 8
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims description 7
LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical class OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims description 7
235000010267 sodium hydrogen sulphite Nutrition 0.000 claims description 7
239000007909 solid dosage form Substances 0.000 claims description 7
235000010323 ascorbic acid Nutrition 0.000 claims description 6
239000011668 ascorbic acid Substances 0.000 claims description 6
229960005070 ascorbic acid Drugs 0.000 claims description 6
238000009472 formulation Methods 0.000 claims description 6
239000008297 liquid dosage form Substances 0.000 claims description 6
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 6
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 6
QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 claims description 5
239000011786 L-ascorbyl-6-palmitate Substances 0.000 claims description 5
239000002253 acid Substances 0.000 claims description 5
235000010385 ascorbyl palmitate Nutrition 0.000 claims description 5
239000005711 Benzoic acid Substances 0.000 claims description 4
ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 claims description 4
XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 4
LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 claims description 4
239000004158 L-cystine Substances 0.000 claims description 4
235000019393 L-cystine Nutrition 0.000 claims description 4
150000007513 acids Chemical class 0.000 claims description 4
239000003513 alkali Substances 0.000 claims description 4
229910052783 alkali metal Inorganic materials 0.000 claims description 4
150000001340 alkali metals Chemical class 0.000 claims description 4
CAYMSCGTKZIVTN-TYILLQQXSA-N alpha-Conidendrin Chemical compound C1([C@@H]2[C@@H]3[C@H](C(OC3)=O)CC=3C=C(C(=CC=32)O)OC)=CC=C(O)C(OC)=C1 CAYMSCGTKZIVTN-TYILLQQXSA-N 0.000 claims description 4
CAYMSCGTKZIVTN-UHFFFAOYSA-N alpha-conidendrin Natural products C1=2C=C(O)C(OC)=CC=2CC(C(OC2)=O)C2C1C1=CC=C(O)C(OC)=C1 CAYMSCGTKZIVTN-UHFFFAOYSA-N 0.000 claims description 4
150000001555 benzenes Chemical class 0.000 claims description 4
235000010233 benzoic acid Nutrition 0.000 claims description 4
235000010290 biphenyl Nutrition 0.000 claims description 4
239000004305 biphenyl Substances 0.000 claims description 4
HNEGQIOMVPPMNR-IHWYPQMZSA-N citraconic acid Chemical compound OC(=O)C(/C)=C\C(O)=O HNEGQIOMVPPMNR-IHWYPQMZSA-N 0.000 claims description 4
229940018557 citraconic acid Drugs 0.000 claims description 4
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 4
235000018417 cysteine Nutrition 0.000 claims description 4
229960002433 cysteine Drugs 0.000 claims description 4
229960003067 cystine Drugs 0.000 claims description 4
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 claims description 4
235000014113 dietary fatty acids Nutrition 0.000 claims description 4
150000005682 diethyl carbonates Chemical class 0.000 claims description 4
235000013399 edible fruits Nutrition 0.000 claims description 4
150000002148 esters Chemical class 0.000 claims description 4
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 4
229930195729 fatty acid Natural products 0.000 claims description 4
239000000194 fatty acid Substances 0.000 claims description 4
150000004665 fatty acids Chemical class 0.000 claims description 4
239000000787 lecithin Substances 0.000 claims description 4
235000010445 lecithin Nutrition 0.000 claims description 4
150000002739 metals Chemical class 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
235000010199 sorbic acid Nutrition 0.000 claims description 4
239000004334 sorbic acid Substances 0.000 claims description 4
229940075582 sorbic acid Drugs 0.000 claims description 4
230000000087 stabilizing effect Effects 0.000 claims description 4
AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 claims description 4
229960000984 tocofersolan Drugs 0.000 claims description 4
235000010384 tocopherol Nutrition 0.000 claims description 4
229960001295 tocopherol Drugs 0.000 claims description 4
229930003799 tocopherol Natural products 0.000 claims description 4
239000011732 tocopherol Substances 0.000 claims description 4
229940042585 tocopherol acetate Drugs 0.000 claims description 4
GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 4
XRSKRSVTUVLURN-UHFFFAOYSA-N 1,3-benzodioxol-4-ol Chemical class OC1=CC=CC2=C1OCO2 XRSKRSVTUVLURN-UHFFFAOYSA-N 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 3
239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 3
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 3
229960002216 methylparaben Drugs 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 3
239000004405 propyl p-hydroxybenzoate Substances 0.000 claims description 3
229960003415 propylparaben Drugs 0.000 claims description 3
239000008299 semisolid dosage form Substances 0.000 claims description 3
230000001225 therapeutic effect Effects 0.000 claims description 3
150000003017 phosphorus Chemical class 0.000 claims description 2
230000002265 prevention Effects 0.000 claims description 2
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 claims description 2
150000001342 alkaline earth metals Chemical class 0.000 claims 3
239000013543 active substance Substances 0.000 claims 2
235000011007 phosphoric acid Nutrition 0.000 claims 2
150000003016 phosphoric acids Chemical class 0.000 claims 2
239000004289 sodium hydrogen sulphite Substances 0.000 claims 2
239000004291 sulphur dioxide Substances 0.000 abstract 1
239000000243 solution Substances 0.000 description 47
238000006243 chemical reaction Methods 0.000 description 15
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
230000015572 biosynthetic process Effects 0.000 description 8
239000011521 glass Substances 0.000 description 7
239000012153 distilled water Substances 0.000 description 6
230000002401 inhibitory effect Effects 0.000 description 6
238000012360 testing method Methods 0.000 description 6
OZAIFHULBGXAKX-UHFFFAOYSA-N 2,2'-azo-bis-isobutyronitrile Substances N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 5
239000003963 antioxidant agent Substances 0.000 description 5
235000006708 antioxidants Nutrition 0.000 description 5
UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 5
239000003814 drug Substances 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
238000011160 research Methods 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
239000003929 acidic solution Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000004128 high performance liquid chromatography Methods 0.000 description 3
239000012286 potassium permanganate Substances 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
229910017604 nitric acid Inorganic materials 0.000 description 2
239000008213 purified water Substances 0.000 description 2
229960001402 tilidine Drugs 0.000 description 2
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
230000002292 Radical scavenging effect Effects 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
235000011054 acetic acid Nutrition 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
239000012084 conversion product Substances 0.000 description 1
229930003836 cresol Natural products 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
WDEFBBTXULIOBB-WBVHZDCISA-N dextilidine Chemical compound C=1C=CC=CC=1[C@@]1(C(=O)OCC)CCC=C[C@H]1N(C)C WDEFBBTXULIOBB-WBVHZDCISA-N 0.000 description 1
239000013583 drug formulation Substances 0.000 description 1
WDEFBBTXULIOBB-UHFFFAOYSA-N ethyl 2-(dimethylamino)-1-phenylcyclohex-3-ene-1-carboxylate Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCC=CC1N(C)C WDEFBBTXULIOBB-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229960005181 morphine Drugs 0.000 description 1
229940065778 narcan Drugs 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
229930015710 phenanthrene alkaloid Natural products 0.000 description 1
150000002987 phenanthrenes Chemical class 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
238000011002 quantification Methods 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000002516 radical scavenger Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
238000007086 side reaction Methods 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
238000013112 stability test Methods 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
239000011787 zinc oxide Substances 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
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Inorganic Chemistry (AREA)
Oil, Petroleum & Natural Gas (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Emergency Medicine (AREA)
Neurology (AREA)
Pain & Pain Management (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Organic Insulating Materials (AREA)
Cereal-Derived Products (AREA)
Medicinal Preparation (AREA)
Detergent Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

SK1092-99A 1997-02-14 1998-02-03 Spôsob stabilizácie naloxonhydrochloridu SK282549B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE19705537		1997-02-14
PCT/EP1998/000556 WO1998035679A1 (de)	1997-02-14	1998-02-03	Stabilisierung von naloxonhydrochlorid

Publications (2)

Publication Number	Publication Date
SK109299A3 SK109299A3 (en)	2000-08-14
SK282549B6 true SK282549B6 (sk)	2002-10-08

Family

ID=7820153

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1092-99A SK282549B6 (sk)	1997-02-14	1998-02-03	Spôsob stabilizácie naloxonhydrochloridu

Country Status (10)

Country	Link
EP (1)	EP0880352B1 (cs)
AT (1)	ATE186643T1 (cs)
CZ (1)	CZ297951B6 (cs)
DE (1)	DE59800046D1 (cs)
ES (1)	ES2141631T3 (cs)
GR (1)	GR3032458T3 (cs)
HU (1)	HU224964B1 (cs)
PL (1)	PL190293B1 (cs)
SK (1)	SK282549B6 (cs)
WO (1)	WO1998035679A1 (cs)

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WO2010103039A1 (en)	2009-03-10	2010-09-16	Euro-Celtique S.A.	Immediate release pharmaceutical compositions comprising oxycodone and naloxone
EA029096B1 (ru)	2010-03-11	2018-02-28	Вайет Ллк	Твердая лекарственная форма для перорального введения, содержащая метилналтрексон
NZ603173A (en)	2010-05-10	2014-10-31	Euro Celtique Sa	Manufacturing of active-free granules and tablets comprising the same
WO2011141490A1 (en)	2010-05-10	2011-11-17	Euro-Celtique S.A.	Combination of active loaded granules with additional actives
CA2795324C (en) *	2012-11-09	2015-07-14	Purdue Pharma	Pharmaceutical compositions comprising hydromorphone and naloxone
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1998
- 1998-02-03 CZ CZ0289699A patent/CZ297951B6/cs not_active IP Right Cessation
- 1998-02-03 WO PCT/EP1998/000556 patent/WO1998035679A1/de not_active Ceased
- 1998-02-03 DE DE59800046T patent/DE59800046D1/de not_active Expired - Lifetime
- 1998-02-03 HU HU0001094A patent/HU224964B1/hu unknown
- 1998-02-03 EP EP98905128A patent/EP0880352B1/de not_active Expired - Lifetime
- 1998-02-03 ES ES98905128T patent/ES2141631T3/es not_active Expired - Lifetime
- 1998-02-03 AT AT98905128T patent/ATE186643T1/de active
- 1998-02-03 SK SK1092-99A patent/SK282549B6/sk not_active IP Right Cessation
- 1998-02-03 PL PL98335249A patent/PL190293B1/pl unknown
2000
- 2000-01-25 GR GR20000400152T patent/GR3032458T3/el unknown

Also Published As

Publication number	Publication date
DE59800046D1 (de)	1999-12-23
HUP0001094A3 (en)	2001-02-28
PL335249A1 (en)	2000-04-10
GR3032458T3 (en)	2000-05-31
HUP0001094A2 (hu)	2000-09-28
ATE186643T1 (de)	1999-12-15
EP0880352B1 (de)	1999-11-17
SK109299A3 (en)	2000-08-14
EP0880352A2 (de)	1998-12-02
HU224964B1 (en)	2006-04-28
ES2141631T3 (es)	2000-03-16
PL190293B1 (pl)	2005-11-30
WO1998035679A1 (de)	1998-08-20
CZ297951B6 (cs)	2007-05-02
CZ289699A3 (cs)	2000-02-16

Legal Events

Date	Code	Title	Description
2018-04-04	MK4A	Patent expired	Expiry date: 20180203

Publication	Publication Date	Title
SK109299A3 (en)	2000-08-14	Stabilization of naloxonhydrochloride
EP2416758B1 (en)	2017-09-06	Antimycotic pharmaceutical composition
AU604061B2 (en)	1990-12-06	Drug compositions stabilized against oxidation
KR890001001B1 (ko)	1989-04-18	안정화된 피록시캄 주사용액의 제조방법
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DE29719704U1 (de)	1998-01-22	Stabile Zubereitungen von Naloxonhydrochlorid
SK9682000A3 (en)	2000-12-11	Novel polyethoxylated castor oil, process of making the same and formulations thereof
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