NO153520B - Fremgangsmaate til fremstilling av et stabilt prepaat inneholdende prostaglandin. - Google Patents
Fremgangsmaate til fremstilling av et stabilt prepaat inneholdende prostaglandin. Download PDFInfo
- Publication number
- NO153520B NO153520B NO800186A NO800186A NO153520B NO 153520 B NO153520 B NO 153520B NO 800186 A NO800186 A NO 800186A NO 800186 A NO800186 A NO 800186A NO 153520 B NO153520 B NO 153520B
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- Prior art keywords
- isoxazol
- preparation
- spiro
- procedure
- aryl
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 9
- 238000002360 preparation method Methods 0.000 title description 6
- 150000003180 prostaglandins Chemical class 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 150000003413 spiro compounds Chemical class 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- -1 phenoxy, phenyl Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 239000012442 inert solvent Substances 0.000 claims 1
- 238000002844 melting Methods 0.000 description 10
- 230000008018 melting Effects 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 239000002253 acid Substances 0.000 description 7
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 4
- FHTOLEVRZHZJRV-UHFFFAOYSA-N 2-[3-[3-(trifluoromethyl)phenyl]-1,2-oxazol-5-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC(C=2C=C(C=CC=2)C(F)(F)F)=NO1 FHTOLEVRZHZJRV-UHFFFAOYSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 description 2
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 2
- MGWWOUDQBGCMFV-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazol-5-yl benzoate Chemical compound C=1C=CC=CC=1C(=O)OC1CC=NO1 MGWWOUDQBGCMFV-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- SNRUBQQJIBEYMU-UHFFFAOYSA-N dodecane Chemical compound CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- QUMDOMSJJIFTCA-UHFFFAOYSA-N 1,1,2-tribromoethane Chemical compound BrCC(Br)Br QUMDOMSJJIFTCA-UHFFFAOYSA-N 0.000 description 1
- CRDOTKAIWZFYMN-UHFFFAOYSA-N 2-(1,2-oxazol-3-yl)benzoic acid Chemical class OC(=O)C1=CC=CC=C1C1=NOC=C1 CRDOTKAIWZFYMN-UHFFFAOYSA-N 0.000 description 1
- WPSPTJSNOXDGPR-UHFFFAOYSA-N 2-(4,5-dihydro-1,2-oxazol-5-yl)benzoic acid Chemical class OC(=O)C1=CC=CC=C1C1ON=CC1 WPSPTJSNOXDGPR-UHFFFAOYSA-N 0.000 description 1
- CIQKIYTVDPOSAM-UHFFFAOYSA-N 2-[3-(2,4-dichlorophenyl)-1,2-oxazol-5-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC(C=2C(=CC(Cl)=CC=2)Cl)=NO1 CIQKIYTVDPOSAM-UHFFFAOYSA-N 0.000 description 1
- SRPSPGJIUDJDIT-UHFFFAOYSA-N 2-[3-[4-(trifluoromethyl)phenyl]-1,2-oxazol-5-yl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC(C=2C=CC(=CC=2)C(F)(F)F)=NO1 SRPSPGJIUDJDIT-UHFFFAOYSA-N 0.000 description 1
- IWTLIIZTPVRRFW-UHFFFAOYSA-N 3-methylidene-2-benzofuran-1-one Chemical compound C1=CC=C2C(=C)OC(=O)C2=C1 IWTLIIZTPVRRFW-UHFFFAOYSA-N 0.000 description 1
- UNDXPKDBFOOQFC-UHFFFAOYSA-N 4-[2-nitro-4-(trifluoromethyl)phenyl]morpholine Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1N1CCOCC1 UNDXPKDBFOOQFC-UHFFFAOYSA-N 0.000 description 1
- LDPAXRKRMWLREH-UHFFFAOYSA-N 5-ethyl-4-propyl-1,3-dioxane Chemical compound CCCC1OCOCC1CC LDPAXRKRMWLREH-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- KOZCZZVUFDCZGG-UHFFFAOYSA-N vinyl benzoate Chemical class C=COC(=O)C1=CC=CC=C1 KOZCZZVUFDCZGG-UHFFFAOYSA-N 0.000 description 1
Classifications
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- 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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/61—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
-
- 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
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Gynecology & Obstetrics (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
Denne oppfinnelse angår en fremgangsmåte for fremstilling av 2-(3-aryl-isoxazol-5-yl)-benzoesyrer med.formelen:
hvor X og Y uavhengig av hverandre er hydrogen, halogen,
lavere alkyl, lavere alkoxy, halogen-lavere-alkyl, fenoxy, fenyl eller cyano.
Belgisk patent 837 454 angir at slike isoxazolyl-benzoesyrer er effektive plantevekstregulerende midler. Isoxa-zol-5-yl-benzoater fremstilles vanligvis ved overføring av isoxazolin-5-yl-benzoat med N-bromsuccinimid eller diklordi-cyanobenzokinon. Isoxazolin-5-yl-benzoater fremstilles imidlertid fra vinylbenzoater som er vanskelige å fremstille.
2-(3-aryl-isoxazol-5-yl)-benzoesyrer som dem som fremstilles ved fremgangsmåten ifølge oppfinnelsen, er også be-skrevet i US patentskrift nr. 4 032 644. De fremstilles der ved dehydratisering av de tilsvarende 2-(5-hydroxy-3-aryl-2-isoxazolin-5-yl)-benzoesyrer med en vandig, fortynnet syre. Også her benyttes isoxazolin-5-yl-benzoesyreforbindelser, hvis fremstilling er besværlig.
Ved hjelp av oppfinnelsen tilveiebrines det nu en ny og vesentlig enklere fremgangsmåte for fremstilling av de 1 innledningsvis angitte forbindelser. Den nye fremgangsmåte er særpreget ved at et 31 -(aryl)-spiro-[isobenzofuran-1(3H),51 (41H)-isoxazol]-3-on med formelen:
hvor X og Y har de ovenfor angitte betydninger, oppvarmes ved en temperatur mellom 30°C og tilbakeløpstemperaturen for oppløsningen.
Som anvendt her er uttrykkene "lavere alkyl" og "lavere alkoxy" ment å innbefatte alkyl- og alkoxygrupper med inntil 5 carbonatomer. Både rettkjedede og forgrenede alkylgrupper er innbefattet.
Uttrykket "halogen-lavere-alkyl" er her anvendt for
å betegne lavere alkylgrupper i hvilke minst ett av hydrogen-atomene, og eventuelt alle, er erstattet med halogenatomer.
Uttrykket "halogen" er anvendt for å betegne klor, brom, fluor og jod.
Oppvarmningen av spiroforbindelsen foretas ved atmos-fære trykk i kort tid, vanligvis i mindre enn 1 time. Ved industrielle anvendelser kan det vise seg å være bekvemt å opp-løse spiroforbindelsene i et passende oppløsningsmiddel og oppvarme oppløsningen for å overføre spiroforbindelsen til den ønskede syre. Mengden av varme som tilføres er ikke kritisk. Overføring ved temperaturer under 100°C er mulig, men vil være meget langsom. Temperaturer over 100°C, og særlig fra 125°C opp til tilbakeløpstemperaturen, vil føre til tilfredsstillende overføring. Oppvarmning av oppløsningen fra temperaturen like over smeltepunktet for spiroutgangsmaterialet til tilbakeløps-temperaturen for oppløsningen foretrekkes imidlertid for å bevirke hurtig og effektiv omdannelse.
Hvilket oppløsningsmiddel som benyttes, er ikke av avgjørende betydning. Et hvilket som helst oppløsningsmiddel som er inert overfor spiroforbindelsen og den ønskede syre og har et. tilstrekkelig høyt kokepunkt (f.eks. over 80"C) , vil være anvendbart. Eksempler på slike passende oppløsningsmidler er o-diklorbenzen, dodecan, 1,2,3-trimethylbenzen, benzyl-ethylether, 1,1,2-tribromethan, 5-ethyl-4-propyl-l,3-dioxan og lignende.
De som utgangsmaterialer anvendte ,3-(aryl)-spiro-[isobenzofuran-1(3H), 5'-(4 ' H)-isoxazol]-3-oner fremstilles enkelt ved å omsette et hitriloxyd med 3-methylenfthalid i henhold til følgende .ligning:
hvor X og Y har de ovenfor angitte betydninger.
De nedenstående eksempler illustrerer oppfinnelsen.
Eksempel 1
Fremstilling av 2-[3-(m-trifluormethylfenyl)-isoxazol-5-yl]-benzoesyre "-2 g 3'-(m-trifluormethylfenyl)-spiro-[isobenzofuran-(3H),5<1>(4<1>H)-isoxazol]-3-on med smeltepunkt 170°C ble anbragt i et reagensglass og oppvarmet i et oljebad ved 200 - 220°C
i 2 timer. NMR viste at reaksjonen var fullstendig og at produktet var den ønskede syre. Råproduktet var et gult fast stoff med smeltepunkt 173 - 175°C. Omkrystallisasjon fra acetonitril ga 1,25 g av et gult fast stoff med smeltepunkt 177 - 178°C.
Alternativt kan 2-[3-(m-trifluormethylfenyl)-isoxazol-5-yl]-benzoesyre fremstilles ved fremgangsmåten i eksempel 2.
Eksempel 2
Fremstilling av 2-[3-(m-trifluormethylfenyl)-isoxazol-5-yl]-benzoesyre
En oppløsning av 1 g 3'-(m-trifluormethylfenyl)-spiro-[isobenzofuran-1(3H),5'(4'H)-isoxazol]-3-on med smeltepunkt 170°C, i 20 ml o-diklorbenzen ble holdt under tilbakeløp i 3,5 timer og ble deretter avkjølt og inndampet i vakuum, hvorved man fikk et gult fast stoff. NMR viste at reaksjonen ennu ikke var fullstendig. Det faste stoff ble igjen oppløst i 20 ml o-diklorbenzen, og oppløsningen ble holdt under tilbakeløp i ytterligere 3 timer, hvoretter den ble avkjølt og inndampet i vakuum, hvorved man fikk et kvantitativt utbytte av den ønskede syre som et blekt gult fast stoff med smeltepunkt 172 - 174°C.
Eksempel 3
Fremstilling av 2-[3-(p-trifluormethylfenyl)-isoxazol-5-yl]-benzoesyre
1,35 g 3'-(p-trifluormethylfenyl)-spiro-[isobenzo-furan-l(3H),5'(4<1>H)-isoxazol]-3-on med smeltepunkt 177 - 178°C ble anbragt i et reagensglass og oppvarmet i et oljebad ved 200 - 220°C i 35 minutter. NMR viste at reaksjonen var fullstendig og at den ønskede syre var fremstilt. Den ble erholdt som et lysebrunt fast stoff med smeltepunkt 198 - 202°C. Omkrystallisasjon fra acetonitril ga 0,92 g ga et gulhvitt fast stoff med smeltepunkt 205 - 207°C.
Anal. beregn, for C17H10<F>3<N>O3: C, 61,27; H, 3,02
Funnet: C, 61,22; H, 3,07.
Eksempel 4
Fremstilling av 2-[3-(2,4-diklorfenyl)-isoxazol-5-yl]-benzoe-syre
135 g 31 -(2,4-diklorfenyl)-spiro-[isobenzofuran-1(3H) , 5'(4'H)-isoxazol]-3-on med smeltepunkt 158 - 161°C ble anbragt i et reagensglass og oppvarmet i et oljebad ved en temperatur på 185 - 190°C i ca. 15 minutter. NMR viste at reaksjonen var fullstendig og at den ønskede syre var dannet. Den ble erholdt som et hvitt, fast stoff med smeltepunkt 181 - 183°C. Omkrystallisasjon fra acetonitril ga 0,75 g ga et hvitt fast stoff med smeltepunkt 182 - 183°C.
Anal. beregn, for: Ci6HgNCl203 : C, 57,86; H, 2,73
Funnet: C, 5 7,61; H, 2,79.
Claims (3)
1. Fremgangsmåte ved fremstilling av 2-(3-aryl-isoxazol-5-yl)-benzoesyrer med formelen:
hvor .X og Y uavhengig av hverandre er hydrogen, halogen, lavere alkyl, lavere alkoxy, halogen-lavere-alkyl, fenoxy, fenyl eller cyano,
karakterisert ved at et 3'-(aryl)-spiro-[isobenzofuran-1(3H),5'(4'H)-isoxazol]-3-on med formelen:
hvor X og Y har de ovenfor angitte betydninger,
oppvarmes ved en temperatur mellom 30°C og tilbakeløps-temperaturen for oppløsningen.
2. Fremgangsmåte ifølge krav 1, karakterisert ved at spiroforbindelsen opp-løses i et inert oppløsningsmiddel.
3. Fremgangsmåte ifølge krav 1 eller 2, for fremstilling av forbindelser hvor X er hydrogen og Y er trifluormethyl, karakterisert ved at en forbindelse med formel (II) hvor X er hydrogen og Y er trifluormethyl, oppvarmes ved en temperatur mellom 125°C og tilbakeløpstempera-turen for oppløsningen, fortrinnsvis ved tilbakeløpstempera-turen .
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE7900737A SE431821B (sv) | 1979-01-29 | 1979-01-29 | Lagringsstabilt, prostaglandininnehallande medicinskt preparat |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO800186L NO800186L (no) | 1980-07-30 |
| NO153520B true NO153520B (no) | 1985-12-30 |
| NO153520C NO153520C (no) | 1986-04-09 |
Family
ID=20337129
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO800186A NO153520C (no) | 1979-01-29 | 1980-01-25 | Fremgangsm¨te til fremstilling av et stabilt preparat inne holdende prostaglandin. |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4352790A (no) |
| JP (1) | JPS55102512A (no) |
| BE (1) | BE881351A (no) |
| DE (1) | DE3001454A1 (no) |
| DK (2) | DK160739C (no) |
| FR (1) | FR2447191A1 (no) |
| GB (1) | GB2041220B (no) |
| NL (1) | NL190693C (no) |
| NO (1) | NO153520C (no) |
| SE (2) | SE431821B (no) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5079009A (en) * | 1979-03-21 | 1992-01-07 | National Research Development Corporation | Controlled release compositions including polyethylene oxide with urethane cross-linking |
| AU537741B2 (en) * | 1979-03-21 | 1984-07-12 | British Technology Group Limited | Controlled release compositions |
| IT1131833B (it) * | 1980-06-20 | 1986-06-25 | Crinos Industria Farmaco | Eccipienti per sostanze spermicide |
| ZA831186B (en) * | 1982-03-22 | 1983-11-30 | Upjohn Ltd | Gelled pge2/triacetin solutions |
| AU546872B2 (en) * | 1982-06-16 | 1985-09-26 | Unilever Plc | Skin treatment compositions containing a fatty acid or ester |
| US4675182A (en) * | 1983-02-12 | 1987-06-23 | Bayer Aktiengesellschaft | Complexes of prostaglandins |
| DE3307816A1 (de) * | 1983-03-02 | 1984-09-06 | Schering AG, 1000 Berlin und 4709 Bergkamen | Prostaglandin-haltiges pharmazeutisches praeparat und seine herstellung |
| GB8403360D0 (en) * | 1984-02-08 | 1984-03-14 | Erba Farmitalia | Pharmaceutical compositions |
| DE3428264A1 (de) * | 1984-07-27 | 1986-03-06 | Schering Ag | Gelhaltige pharmazeutische zubereitungen |
| IE59361B1 (en) | 1986-01-24 | 1994-02-09 | Akzo Nv | Pharmaceutical preparation for obtaining a highly viscous hydrogel or suspension |
| JP2590358B2 (ja) * | 1988-03-01 | 1997-03-12 | 正雄 五十嵐 | 子宮内膜症治療用の子宮内又は膣内投与製剤 |
| JPH03220201A (ja) * | 1988-11-18 | 1991-09-27 | Eisai Co Ltd | プロスタグランジン類と多糖類の結合体 |
| CH678697A5 (no) * | 1989-04-03 | 1991-10-31 | Warner Lambert Co | |
| US5491171A (en) * | 1991-11-08 | 1996-02-13 | Kyoto Pharmaceutical Industries, Ltd. | Pharmaceutical preparation containing prostaglandin compound for rectal or vaginal administration |
| US6946442B2 (en) * | 1994-11-30 | 2005-09-20 | Asif Syed Ahmed | Method of hastening cervical ripening |
| JPH11506100A (ja) * | 1995-06-01 | 1999-06-02 | ジー．ディー．サール アンド カンパニー | ミソプロストールの安定化された分散系 |
| KR20010021625A (ko) | 1997-07-09 | 2001-03-15 | 추후보정 | 개선된 남성발기 기능장애 치료방법 및 그 조성물 |
| US6103765A (en) | 1997-07-09 | 2000-08-15 | Androsolutions, Inc. | Methods for treating male erectile dysfunction |
| FR2766709B1 (fr) | 1997-07-31 | 2000-04-07 | Dominique Cingotti | Procede pour la preparation d'un extrait de principes actifs sous forme de microgranules a base de fibres alimentaires entierement solubles destines a differentes formes galeniques |
| US6031002A (en) * | 1998-05-01 | 2000-02-29 | Michael Ebert | Method for enhancing female sexual response and a composition therefor |
| US5891915A (en) * | 1998-05-01 | 1999-04-06 | Wysor; Michael S. | Method for enhancing female sexual response and an ointment therefor |
| US6825234B2 (en) | 1998-12-10 | 2004-11-30 | Nexmed (Holdings) , Inc. | Compositions and methods for amelioration of human female sexual dysfunction |
| US6486207B2 (en) | 1998-12-10 | 2002-11-26 | Nexmed (Holdings), Inc. | Compositions and methods for amelioration of human female sexual dysfunction |
| US20070191320A1 (en) * | 1998-12-10 | 2007-08-16 | Nexmed Holdings, Inc. | Methods of treatment for female sexual arousal disorder |
| GR1004266B (el) * | 2001-04-30 | 2003-06-18 | Ηλιας Κ. Παπαδοπουλος | Φαρμακευτικο παρασκευασμα για την διαγνωση και θεραπεια της στυτικης δυσλειτουργιας |
| US20050181030A1 (en) * | 2003-01-03 | 2005-08-18 | Mo Y. J. | Topical stabilized prostaglandin E compound dosage forms |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3948254A (en) * | 1971-11-08 | 1976-04-06 | Alza Corporation | Novel drug delivery device |
| US3875300A (en) | 1972-12-18 | 1975-04-01 | Ortho Pharma Corp | Composition for sustained release of a medicament and method of using same |
| US3888975A (en) * | 1972-12-27 | 1975-06-10 | Alza Corp | Erodible intrauterine device |
| US4036954A (en) * | 1973-11-02 | 1977-07-19 | Yamanouchi Pharmaceutical Co., Ltd. | Stable prostaglandin E group-containing formulation |
| AR205997A1 (es) | 1973-11-21 | 1976-06-23 | American Cyanamid Co | Resina de poliester normalmente solida biodegradable e hidrolizable |
| CH616694A5 (en) * | 1974-06-27 | 1980-04-15 | Ciba Geigy Ag | Process for the preparation of crosslinked, water-insoluble, hydrophilic copolymers |
| US4107288A (en) | 1974-09-18 | 1978-08-15 | Pharmaceutical Society Of Victoria | Injectable compositions, nanoparticles useful therein, and process of manufacturing same |
| JPS5256148A (en) * | 1975-10-16 | 1977-05-09 | Agency Of Ind Science & Technol | Process for preparing active substances having improved |
| GB1554783A (en) | 1976-01-05 | 1979-10-31 | Population Res Inc | Pharmaceutical compositions for use in the permanent sterilization of female animals |
| DE2709804C2 (de) * | 1976-03-12 | 1986-03-13 | Ono Pharmaceutical Co. Ltd., Osaka | Prostaglandin-analoga, Verfahren zu ihrer Herstellung, sowie diese enthaltende pharmazeutische Zusammensetzungen |
| GB1551620A (en) * | 1976-12-13 | 1979-08-30 | Ici Ltd | Delivery means for biologically active agents |
-
1979
- 1979-01-29 SE SE7900737A patent/SE431821B/sv not_active IP Right Cessation
- 1979-12-17 SE SE7910354A patent/SE442167B/sv not_active IP Right Cessation
-
1980
- 1980-01-14 GB GB8001176A patent/GB2041220B/en not_active Expired
- 1980-01-16 US US06/112,563 patent/US4352790A/en not_active Expired - Lifetime
- 1980-01-16 DE DE19803001454 patent/DE3001454A1/de active Granted
- 1980-01-18 JP JP519880A patent/JPS55102512A/ja active Granted
- 1980-01-23 NL NL8000426A patent/NL190693C/xx not_active IP Right Cessation
- 1980-01-25 NO NO800186A patent/NO153520C/no unknown
- 1980-01-25 BE BE0/199113A patent/BE881351A/fr not_active IP Right Cessation
- 1980-01-28 DK DK033580A patent/DK160739C/da not_active IP Right Cessation
- 1980-01-28 FR FR8001797A patent/FR2447191A1/fr active Granted
-
1986
- 1986-07-03 DK DK316186A patent/DK160740C/da not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| JPS55102512A (en) | 1980-08-05 |
| DK160740C (da) | 1991-09-30 |
| DE3001454C2 (no) | 1990-05-10 |
| US4352790A (en) | 1982-10-05 |
| DE3001454A1 (de) | 1980-08-07 |
| DK316186A (da) | 1986-07-03 |
| GB2041220A (en) | 1980-09-10 |
| GB2041220B (en) | 1983-07-27 |
| NL190693C (nl) | 1994-07-01 |
| DK33580A (da) | 1980-07-30 |
| BE881351A (fr) | 1980-05-16 |
| NL8000426A (nl) | 1980-07-31 |
| NL190693B (nl) | 1994-02-01 |
| SE7910354L (sv) | 1980-07-30 |
| SE431821B (sv) | 1984-03-05 |
| DK316186D0 (da) | 1986-07-03 |
| NO800186L (no) | 1980-07-30 |
| SE7900737L (sv) | 1980-07-30 |
| DK160739C (da) | 1991-09-30 |
| FR2447191A1 (fr) | 1980-08-22 |
| FR2447191B1 (no) | 1983-07-22 |
| SE442167B (sv) | 1985-12-09 |
| DK160740B (da) | 1991-04-15 |
| JPH0140013B2 (no) | 1989-08-24 |
| NO153520C (no) | 1986-04-09 |
| DK160739B (da) | 1991-04-15 |
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