LT3697B - Process for the manufacture of budesonide - Google Patents
Process for the manufacture of budesonide Download PDFInfo
- Publication number
- LT3697B LT3697B LTIP1729A LTIP1729A LT3697B LT 3697 B LT3697 B LT 3697B LT IP1729 A LTIP1729 A LT IP1729A LT IP1729 A LTIP1729 A LT IP1729A LT 3697 B LT3697 B LT 3697B
- Authority
- LT
- Lithuania
- Prior art keywords
- reaction
- budesonide
- methanol
- catalyst
- water
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 11
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 title claims description 12
- 229960004436 budesonide Drugs 0.000 title claims description 12
- 238000004519 manufacturing process Methods 0.000 title abstract 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 7
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 15
- 238000006243 chemical reaction Methods 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 4
- 239000011541 reaction mixture Substances 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 239000004215 Carbon black (E152) Substances 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 3
- 229930195733 hydrocarbon Natural products 0.000 claims description 3
- 150000002430 hydrocarbons Chemical class 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 2
- 239000013078 crystal Substances 0.000 claims description 2
- -1 naphtha Chemical class 0.000 claims description 2
- 239000002253 acid Substances 0.000 abstract description 3
- SEKYBDYVXDAYPY-ILNISADRSA-N (8s,9s,10r,11s,13s,14s,16r,17s)-11,16,17-trihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-3-one Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 SEKYBDYVXDAYPY-ILNISADRSA-N 0.000 abstract 2
- 239000000047 product Substances 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- GUSVXFPRNUPMFZ-ZEVBYOGFSA-N 16a-Hydroxyprednisolone Chemical compound C[C@]12C[C@@H](O)[C@H]3[C@@H](CCC4=CC(=O)C=C[C@]34C)[C@@H]1C[C@H](O)[C@]2(O)CC(O)=O GUSVXFPRNUPMFZ-ZEVBYOGFSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- JXDZSEUDHVTGSK-UHFFFAOYSA-N acetonitrile butanal Chemical compound C(C)#N.C(CCC)=O JXDZSEUDHVTGSK-UHFFFAOYSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 description 1
- 229940005991 chloric acid Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- C07J71/0026—Oxygen-containing hetero ring cyclic ketals
- C07J71/0031—Oxygen-containing hetero ring cyclic ketals at positions 16, 17
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
- C07J5/0061—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16
- C07J5/0092—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa substituted in position 16 by an OH group free esterified or etherified
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Paper (AREA)
- Load-Bearing And Curtain Walls (AREA)
Description
butanaliu dioksane, katalizatoriumi naudojant chloro perrūgštį. Produktas išskiriamas, reakcijos mišinį skiedžiant metileno chloridu. Neutralizavimas atliekamas, plaunant vandeniniu kalio karbonatu ir vandeniliu. Toliau seka tirpiklio nugarinimas ir kristalinimas iš eterio/ligroino. Tolimesnis produkto valymas atliekamas chromatografijos būdu, pvz. naudojant Sephadex tipo įrenginį. Pagrindiniais dioksano trūkumais yra jo skvarbumas pro odą, sugebėjimas sudaryti peroksidą. Kitu šio žinomo būdo trūkumu yra chloro perrūgštis, esanti stipriu oksidatoriumi. Naudojant šį katalizatorių, pablogėja reakcijos metu išsiskiriančio produkto kokybė. Dėl to, savo ruožtu, tolimesnis apdirbimas bei išgryninimas tampa sudėtingu ir brangiu.
Šio išradimo tikslas - sukurti naują būdą su žymiai kokybiškesne reakcija ir su paprastesnių bei ekonomiškesniu produkto išvalymo ir apdirbimo procesu.
Šį tikslą pasiekti leidžia šį išradimą atitinkantis procesas. Jo metu reakcija vykdoma acetonitrile, katalizatoriumi naudojant p-tolueno sulforūgštį.
Mažiau bazinio (palyginus su dioksanu) tirpiklio acetonitrilo ir silpnesnės, t.y. nesančios oksidatoriumi, p-tolueno sulforūgšties suderinimo dėka reakcija tampa žymiai kokybiškesnė. Palyginus su aukščiau aptartu dioksano bei chloro perrūgšties panaudojimu pagrįstu procesu, dabar išvalymas bei apdirbimas supaprastėja ir tampa ekonomiškesniais.
Pagal vieną iš patogiausių šio išradimo įgyvendinimo variantų reakcija nutraukiama, tuo tikslu papildomai įpilant vandens ir pakoreguojant reakcijos mišinio pH. Tai gali būti atliekama, į vandenį papildomai įpilant natrio hidrokarbonato. Tuomet įvyksta produkto kristalizacija. Kristalai nufiltruojami, ištirpinami metileno chloride ir metanolyje, o po to kristalizuojami, tuo tikslu įpilant tinkamo angliavandenilio, tokio, kai ligroinas, heksanas, cikloheksanas arba heptanas ir gaunamas nevalytas produktas. Atlikus jo perkristalinimą metanolyje/vandenyje, gaunamas grynas budezonidas.
Šį išradimą atitinkantis budezonido gamybos procesas vyksta dviem etapais.
Etapas. Nevalytas budezonidas.
Įvykdoma 16a-hidroksiprednizolono reakcija su butanaliu acetonitrile. Kaip katalizatoriaus įdedama p-tolueno sulforūgšties. Reakcijos mišinys skiedžiamas vandeniu bei vandeniniu natrio hidrokarbonato tirpalu. Ataušinus iki 5-15°C, kristalizuotas produktas nufiltruojamas ir plaunamas vandeniu. Po to drėgna arba išdžiovinta medžiaga ištirpinama metileno chloride. Jeigu buvo naudojama drėgna medžiaga, pašalinama skiedimo metu susidariusi vandeninė fazė. Įdedama metanolio ir susidaręs nevalytas budezonidas nusodinamas, tuo tikslu įpilant ligroino arba kitokio tinkamo angliavandenilio (pvz., heksano, heptano ar cikloheksano), kuris po to nufiltruojamas.
Etapas. Budezonidas.
Nuvalytas budezonidas ištirpinamas metanolyje maždaug 60°C temperatūroje. Tirpalas nufiltruojamas pro tankų filtrą ir atliekamas produkto kristalizavimas, tuo tikslu įpilant vandens. Po aušinimo iki 520°C, filtravimo ir plovimo metanoliu/vandeniu budezonidas džiovinamas vakuume 40-45°C temperatūroje.
Palyginus su iki šiol žinomais procesais, šis yra paprastesnis, ekonomiškesnis ir mažiau pavojingas sveikatai.
Darbinis pavyzdys
Reakcija vykdoma azote. 15,4 g p-tolueno sulforūgšties ištirpinama 200 ml acetonitrilo. Į šį tirpalą įpilama 50,0 g 16a-dihidroksiprednizolono ir
17,6 g butanalio. Temperatūra pakyla iki 25°C. Per 30 min. didžioji medžiagos dalis ištirpsta. Netrukus po to produktas pradeda kristalizuotis. Po 3 valandų reakcija nutraukiama, įpilama 75 ml vandeninio prisotinto natrio hidrokarbonato tirpalo ir tada prasideda produkto kristalizacija. Išdžiovintas produktas ištirpinamas metileno chloride ir metanolyje ir kristalizuojamas, tuo tikslu įpilant ligroino (barometrinis slėgis - 40-65). Susidaro grynas budezonidas.
Nuvalytas budezonidas perkristalinamas iš metanolio vandens. Gaunamas grynas budezonidas su izomerų santykiu A:B 1:1 (aukšto slėgio skysčių chromatografija), [a]25 100-0° (c = 0,2; CH2CI2); M+430 (teoriškai 430,5).
Claims (3)
- Apibrėžtis1. (22 R,S)-16a, 17a-butilidendioksi-11 β, 21-dihidroksipregna1,4-dien-3,20-dionoCH2OH ch2ch2ch2H (i) gavimo būdas, kurio metu 11 β, 16α, 17α, 21-tetrahidroksipregna 1,4-dien3,20-dionas ch2oh tirpiklyje dalyvaujant katalizatoriui reaguoja su butanaliu CH3CH2CH2CHO, besiskiriantis tuo, kad reakcija vyksta acetonitrile, katalizatoriumi naudojant p-tolueno sulforūgštį.
- 2. Gavimo būdas pagal 1 punktą, besiskiriantis tuo, kad reakcija nutraukia, įpilant vandens ir pakoreguojant reakcijos mišinio pH.
- 3. Gavimo būdas pagal 1 arba 2 punktą, besiskiriantis tuo kad reakcijai baigiantis susidarantys kristalai nufiltruojami, ištirpinami metileno chloride ir metanolyje, o po to kristalizuojami, tuo tikslu įpilant tinkamo angliavandenilio, tokio kaip ligroinas, heksanas, cikloheksanas ar heptanas ir susidaro nevalytas produktas, kuris po to perkristalinamas metanolyje/vandenyje ir gaunamas grynas budezonidas.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE8903219A SE8903219D0 (sv) | 1989-10-02 | 1989-10-02 | Process for the manufacture of budesonide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| LTIP1729A LTIP1729A (en) | 1995-07-25 |
| LT3697B true LT3697B (en) | 1996-02-26 |
Family
ID=20377019
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LTIP1729A LT3697B (en) | 1989-10-02 | 1993-12-30 | Process for the manufacture of budesonide |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US5556964A (lt) |
| EP (1) | EP0494942B1 (lt) |
| JP (1) | JP2965352B2 (lt) |
| KR (1) | KR0160527B1 (lt) |
| AT (1) | ATE130310T1 (lt) |
| AU (1) | AU632864B2 (lt) |
| BG (1) | BG61608B1 (lt) |
| BR (1) | BR9007700A (lt) |
| CA (1) | CA2065861C (lt) |
| CY (1) | CY2084B1 (lt) |
| DE (1) | DE69023664T2 (lt) |
| DK (1) | DK0494942T3 (lt) |
| ES (1) | ES2079491T3 (lt) |
| FI (1) | FI103204B (lt) |
| HK (1) | HK52097A (lt) |
| HU (1) | HU212576B (lt) |
| LT (1) | LT3697B (lt) |
| LV (1) | LV10283B (lt) |
| NO (1) | NO178827C (lt) |
| RO (1) | RO110947B1 (lt) |
| RU (1) | RU2048472C1 (lt) |
| SE (1) | SE8903219D0 (lt) |
| SG (1) | SG43344A1 (lt) |
| UA (1) | UA26860C2 (lt) |
| WO (1) | WO1991004984A1 (lt) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6028190A (en) | 1994-02-01 | 2000-02-22 | The Regents Of The University Of California | Probes labeled with energy transfer coupled dyes |
| US6166024A (en) | 1995-03-30 | 2000-12-26 | Mayo Foundation For Medical Education And Research | Use of topical azathioprine and thioguanine to treat colorectal adenomas |
| IT1291288B1 (it) | 1997-04-30 | 1999-01-07 | Farmabios Srl | Processo per la preparazione di 16,17 acetali di derivati pregnanici con controllo della distribuzione epimerica al c-22. |
| SE9704186D0 (sv) * | 1997-11-14 | 1997-11-14 | Astra Ab | New composition of matter |
| US6266556B1 (en) | 1998-04-27 | 2001-07-24 | Beth Israel Deaconess Medical Center, Inc. | Method and apparatus for recording an electroencephalogram during transcranial magnetic stimulation |
| FR2782823B1 (fr) | 1998-09-01 | 2000-11-17 | Neopost Ind | Procede d'impression thermique |
| US6234167B1 (en) | 1998-10-14 | 2001-05-22 | Chrysalis Technologies, Incorporated | Aerosol generator and methods of making and using an aerosol generator |
| MY136453A (en) | 2000-04-27 | 2008-10-31 | Philip Morris Usa Inc | "improved method and apparatus for generating an aerosol" |
| US6883516B2 (en) | 2000-04-27 | 2005-04-26 | Chrysalis Technologies Incorporated | Method for generating an aerosol with a predetermined and/or substantially monodispersed particle size distribution |
| US6491233B2 (en) | 2000-12-22 | 2002-12-10 | Chrysalis Technologies Incorporated | Vapor driven aerosol generator and method of use thereof |
| US6501052B2 (en) | 2000-12-22 | 2002-12-31 | Chrysalis Technologies Incorporated | Aerosol generator having multiple heating zones and methods of use thereof |
| US6681998B2 (en) | 2000-12-22 | 2004-01-27 | Chrysalis Technologies Incorporated | Aerosol generator having inductive heater and method of use thereof |
| US7077130B2 (en) | 2000-12-22 | 2006-07-18 | Chrysalis Technologies Incorporated | Disposable inhaler system |
| US6701921B2 (en) | 2000-12-22 | 2004-03-09 | Chrysalis Technologies Incorporated | Aerosol generator having heater in multilayered composite and method of use thereof |
| US6799572B2 (en) | 2000-12-22 | 2004-10-05 | Chrysalis Technologies Incorporated | Disposable aerosol generator system and methods for administering the aerosol |
| US20030055026A1 (en) | 2001-04-17 | 2003-03-20 | Dey L.P. | Formoterol/steroid bronchodilating compositions and methods of use thereof |
| US6568390B2 (en) | 2001-09-21 | 2003-05-27 | Chrysalis Technologies Incorporated | Dual capillary fluid vaporizing device |
| US6640050B2 (en) | 2001-09-21 | 2003-10-28 | Chrysalis Technologies Incorporated | Fluid vaporizing device having controlled temperature profile heater/capillary tube |
| US6804458B2 (en) | 2001-12-06 | 2004-10-12 | Chrysalis Technologies Incorporated | Aerosol generator having heater arranged to vaporize fluid in fluid passage between bonded layers of laminate |
| US6681769B2 (en) | 2001-12-06 | 2004-01-27 | Crysalis Technologies Incorporated | Aerosol generator having a multiple path heater arrangement and method of use thereof |
| US6701922B2 (en) | 2001-12-20 | 2004-03-09 | Chrysalis Technologies Incorporated | Mouthpiece entrainment airflow control for aerosol generators |
| TWI359675B (en) | 2003-07-10 | 2012-03-11 | Dey L P | Bronchodilating β-agonist compositions |
| US7367334B2 (en) | 2003-08-27 | 2008-05-06 | Philip Morris Usa Inc. | Fluid vaporizing device having controlled temperature profile heater/capillary tube |
| US20070020196A1 (en) * | 2003-12-31 | 2007-01-25 | Pipkin James D | Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid prepared from a unit dose suspension |
| US20070020298A1 (en) * | 2003-12-31 | 2007-01-25 | Pipkin James D | Inhalant formulation containing sulfoalkyl ether gamma-cyclodextrin and corticosteroid |
| US20070020299A1 (en) | 2003-12-31 | 2007-01-25 | Pipkin James D | Inhalant formulation containing sulfoalkyl ether cyclodextrin and corticosteroid |
| WO2005088655A1 (en) * | 2004-03-12 | 2005-09-22 | The Provost Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin | A magnetoresistive medium |
| US20070160542A1 (en) * | 2005-12-20 | 2007-07-12 | Verus Pharmaceuticals, Inc. | Methods and systems for the delivery of corticosteroids having an enhanced pharmacokinetic profile |
| US20070249572A1 (en) * | 2005-12-20 | 2007-10-25 | Verus Pharmaceuticals, Inc. | Systems and methods for the delivery of corticosteroids |
| US20070197486A1 (en) * | 2005-12-20 | 2007-08-23 | Verus Pharmaceuticals, Inc. | Methods and systems for the delivery of corticosteroids |
| US20070185066A1 (en) * | 2005-12-20 | 2007-08-09 | Verus Pharmaceuticals, Inc. | Systems and methods for the delivery of corticosteroids |
| US20070191323A1 (en) * | 2006-02-15 | 2007-08-16 | Verus Pharmaceuticals, Inc. | Stable corticosteroid mixtures |
| US12370352B2 (en) | 2007-06-28 | 2025-07-29 | Cydex Pharmaceuticals, Inc. | Nasal and ophthalmic delivery of aqueous corticosteroid solutions |
| CN102060906B (zh) * | 2010-12-23 | 2013-01-16 | 鲁南贝特制药有限公司 | 一种r布地奈德的制备方法 |
| EP3250211B1 (en) * | 2015-01-30 | 2021-12-22 | Coral Drugs Pvt. Ltd. | Novel process for preparation of glucocorticoid steroids |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3197469A (en) * | 1958-08-06 | 1965-07-27 | Pharmaceutical Res Products In | 16, 17-acetals and ketals of 6-halo-16, 17-dihydroxy steroids of the pregnane seriesand intermediates therefor |
| US3077471A (en) * | 1961-08-04 | 1963-02-12 | Olin Mathieson | Steroids of the 19-norpregnane series |
| SE378109B (lt) * | 1972-05-19 | 1975-08-18 | Bofors Ab | |
| SE8008524L (sv) * | 1980-12-04 | 1982-06-05 | Draco Ab | 4-pregnen-derivat, ett forfarande for deras framstellning, beredning och metod for behandling av inflammatoriska tillstand |
| IT1196142B (it) * | 1984-06-11 | 1988-11-10 | Sicor Spa | Procedimento per la preparazione di 16,17-acetali di derivati pregnanici e nuovi composti ottenuti |
| SE8604059D0 (sv) * | 1986-09-25 | 1986-09-25 | Astra Pharma Prod | A method of controlling the epimeric distribution in the preparation of 16,17-acetals of pregnane derivatives |
-
1989
- 1989-10-02 SE SE8903219A patent/SE8903219D0/xx unknown
-
1990
- 1990-09-27 JP JP2514161A patent/JP2965352B2/ja not_active Expired - Lifetime
- 1990-09-27 ES ES90915222T patent/ES2079491T3/es not_active Expired - Lifetime
- 1990-09-27 EP EP90915222A patent/EP0494942B1/en not_active Expired - Lifetime
- 1990-09-27 DK DK90915222.5T patent/DK0494942T3/da active
- 1990-09-27 AU AU65309/90A patent/AU632864B2/en not_active Expired
- 1990-09-27 RU SU905011922A patent/RU2048472C1/ru active
- 1990-09-27 WO PCT/SE1990/000619 patent/WO1991004984A1/en not_active Ceased
- 1990-09-27 DE DE69023664T patent/DE69023664T2/de not_active Expired - Lifetime
- 1990-09-27 HU HU9201064A patent/HU212576B/hu unknown
- 1990-09-27 AT AT90915222T patent/ATE130310T1/de not_active IP Right Cessation
- 1990-09-27 RO RO92-200446A patent/RO110947B1/ro unknown
- 1990-09-27 CA CA002065861A patent/CA2065861C/en not_active Expired - Lifetime
- 1990-09-27 KR KR1019920700728A patent/KR0160527B1/ko not_active Expired - Lifetime
- 1990-09-27 BR BR909007700A patent/BR9007700A/pt not_active IP Right Cessation
- 1990-09-27 UA UA94010159A patent/UA26860C2/uk unknown
- 1990-11-27 SG SG1996008769A patent/SG43344A1/en unknown
-
1992
- 1992-03-30 NO NO921233A patent/NO178827C/no not_active IP Right Cessation
- 1992-04-01 FI FI921426A patent/FI103204B/fi active
- 1992-04-01 BG BG96166A patent/BG61608B1/bg unknown
-
1993
- 1993-06-30 LV LVP-93-858A patent/LV10283B/xx unknown
- 1993-12-30 LT LTIP1729A patent/LT3697B/lt not_active IP Right Cessation
-
1994
- 1994-12-16 US US08/357,773 patent/US5556964A/en not_active Expired - Lifetime
-
1997
- 1997-04-24 HK HK52097A patent/HK52097A/en not_active IP Right Cessation
-
1998
- 1998-10-16 CY CY9802084A patent/CY2084B1/xx unknown
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