ME00907B - Farmaceutske formulacije koje sadrže vorikonazol - Google Patents
Farmaceutske formulacije koje sadrže vorikonazolInfo
- Publication number
- ME00907B ME00907B MEP-1999-681A MEP1999681A ME00907B ME 00907 B ME00907 B ME 00907B ME P1999681 A MEP1999681 A ME P1999681A ME 00907 B ME00907 B ME 00907B
- Authority
- ME
- Montenegro
- Prior art keywords
- voriconazole
- formulation according
- pharmaceutically acceptable
- formula
- cyclodextrin
- Prior art date
Links
- BCEHBSKCWLPMDN-MGPLVRAMSA-N voriconazole Chemical compound C1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=NC=C1F BCEHBSKCWLPMDN-MGPLVRAMSA-N 0.000 title claims abstract description 19
- 229960004740 voriconazole Drugs 0.000 title claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 8
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 238000009472 formulation Methods 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- -1 alkali metal salt Chemical class 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 238000007911 parenteral administration Methods 0.000 claims description 2
- 229910006069 SO3H Inorganic materials 0.000 claims 2
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 2
- 229920000858 Cyclodextrin Polymers 0.000 description 7
- NZAQRZWBQUIBSF-UHFFFAOYSA-N 4-(4-sulfobutoxy)butane-1-sulfonic acid Chemical compound OS(=O)(=O)CCCCOCCCCS(O)(=O)=O NZAQRZWBQUIBSF-UHFFFAOYSA-N 0.000 description 5
- 239000000243 solution Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 125000002947 alkylene group Chemical group 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- VNDHXHMRJVTMTK-WZVRVNPQSA-H hexasodium 4-[[(1S,3R,5R,6S,8R,10R,11S,13R,15R,16S,18R,20R,21S,23R,25R,26S,28R,30R,31S,33R,35R,36R,37R,38R,39R,40R,41R,42R,43R,44R,45R,46R,47R,48R,49R)-36,37,38,39,40,41,42,43,44,45,46,47,48,49-tetradecahydroxy-10-(hydroxymethyl)-15,20,25,30,35-pentakis(4-sulfonatobutoxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontan-5-yl]methoxy]butane-1-sulfonate Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].OC[C@H]1O[C@@H]2O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCCCCS([O-])(=O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCCCCS([O-])(=O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCCCCS([O-])(=O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCCCCS([O-])(=O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCCCCS([O-])(=O)=O)O[C@H]3[C@H](O)[C@@H](O)[C@H](O[C@@H]3COCCCCS([O-])(=O)=O)O[C@H]1[C@H](O)[C@H]2O VNDHXHMRJVTMTK-WZVRVNPQSA-H 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 206010017533 Fungal infection Diseases 0.000 description 1
- 206010019909 Hernia Diseases 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- WHGYBXFWUBPSRW-FEYSZYNQSA-N β-dextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)C(O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FEYSZYNQSA-N 0.000 description 1
Classifications
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6949—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
- A61K47/6951—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nanotechnology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biophysics (AREA)
- Biotechnology (AREA)
- General Engineering & Computer Science (AREA)
- Medical Informatics (AREA)
- General Chemical & Material Sciences (AREA)
- Crystallography & Structural Chemistry (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Inorganic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
Pronalazak obezbeđuje farmaceutsku formulaciju koja obuhvata vorikonazol ili njegov farmaceutski prihvatljiv derivat i ciklodekstrinski derivat formule 1:gde R1a-g, R2a-g i R3a-g svaki nezavisno predstavlja OH ili O(CH2)4S03H; uz pretpostavku da bar jedan od R1a-g predstavalja O(CH)4S03H; ili njegovu farmaceutski prihvatljivu so Pronalazak obezbeđuje farmaceutsku formulaciju koja obuhvata vorikonazol ili njegov farmaceutski prihvatljiv derivat i ciklodekstrinski derivat formule 1:gde R 1a-g , R 2a-g i R 3a-g svaki nezavisno predstavlja OH ili O(CH 2 )4S0 3 H; uz pretpostavku da bar jedan od R 1a-g predstavalja O(CH ) 4 S0 3 H; ili njegovu farmaceutski prihvatljivu so
Description
Oblast tehnike
Pronalazak spada u oblast preparativne hernije.
Tehnički problem
Ovaj pronalazak se odnosi na novu farmaceutsku formulaciju vorikonazola sa sulfobutiletar (3-ciklodekstrinom.
Stanje tehnike
Vorikonazol je objavljen u Evropskoj patentnoj prijavi 0440372 (videti primer 7). Vorikonazol ima sledeću strukturu:
i primenjiv je u tretiranju fungalnih infekcija. Vorikonazol ima nisku vodenu rastvorljivost (0,2 mg/ml na pH=3) i nije stabilan u vodi (neaktivan enantiomer se formira iz rekombinacije retro-aldolnih proizvoda hidrolize). Tako, razvoj vodene intravenozne formulacije sa dovoljnim vekom trajanja je težak. Ovi problemi su uvećani sa semi-polarnom prirodom jedinjenja (log D =1,8) što znači da se ovo jedinjenje uglavnom solibilizira pomoću uobičajenih sredstava, takvih kao što su ulja, površinski aktivni agensi ili sa vodom mešljivi ko-rastvarači.
Evropska patentna prijava 0440372 ističe da u njoj opisana jedinjenja mogu da budu formulisana sa ciklodekstrinom: međutim, sada se sumnja da nederivatizovan ili nemetabolizovan ciklodekstrin ima toksične efekte na organizam i tako je nepodesan kao farmaceutski ekscipient, naročito kada se primeni parenteralno.
Međunarodna patentna prijava WO 91/11172 opisuje sulfoalkiletar ciklodekstrinske derivate formule A:
gde
n je 4, 5 ili 6;
R1-9 svaki nezavisno predstavlja 0 ili 0-(C2-6 alkilen)-SO‘ uz predpostavku da bar jedan od R1 i R2 je 0-(C2-6 alkilen)-SO'; i
S1-9 svaki nezavisno predstavlja farmaceutski prihvatljiv katjon (takav kao što je H+ ili Na+).
Opis rešenja tehničkog problema
Sada je nađeno da rastvorljivost vorikonazola u vodi može da bude uvećana pomoću molekulskog kapsuliranja sa sulfoalkiletar ciklodekstrinskim derivatima tipa koji je opisan u Međunarodnoj patentnoj prijavi WO 91/11172, naročito kada nje 5 (/3-ciklodekstrinski derivat) a ciklodekstrinski prsten je supstituisan sa sulfobutil grupama.
Tako, prema pronalasku, obezbeđena je farmaceutska formulacija koja obuhvata vorikonazol ili njegov farmaceutski prihvatljiv derivat i ciklodekstrinski derivat formule I:
gde
Rla-g, R2a-g i R3a-g svaki nezavisno predstavlja OH ili O(CH2)4S03H; uz predpostavku da bar jedan od Rla-g predstavlja 0(CH2)4S03H; ili njegovu farmaceutski prihvatljivu so.
Farmaceutski prihvatljive soli od posebnog interesa su soli O(CH2)4S03H grupa, na primer, soli alkalnog metala, takve kao što su soli natrijuma.
Poželjno, prosečan broj O(CH2)4SO3H grupa po molekulu formule I je u oblasti od 6,1 do 6,9, na primer 6,5. Ovo poboljšava molekulsko kapsuliranje što dovodi do poboljšane rastvorljivosti vorikonazola. Ovaj efekat ne treba očekivati pošto povećanje stepena supstitucije povećava sterne smetnje oko šupljine ciklodekstrina i treba očekivati da smanjuje efikasnost kompleksiranja.
Poželjno je da svaka O(CH2)4S03H grupa bude prisutna u obliku soli alkalnog metala (takve kao što je so natrijuma). Ovo poboljšava afinitet molekula za vorikonazol, stoje neočekivano pošto vorikonazol nije naelektrisan.
Poželjno, formulacija je za parenteralnu primenu, na primer, i.v. primena.
Vodena stabilnost kompleksa vorikonazol-diklodekstrinski derivat se dalje uvećava pomoću liofilizacije (suvo-smrzavanje). Ciklodekstrinski derivati koji se koriste u formulacijama prema pronalsku daju konačni liofilizirani proizvod koji je
akomodiran na visoke nivoe vlage (do 3,0%) bez štetnog efekta na stabilnost. Dalje, korišćenje takvih ciklodekstrinskih derivata kontroliše i minimizira formiranje neaktivnog enantiomera vorikonazola.
Uopšteno, u vodenim intravenskim i intramuskularnim formulacijama prema pronalasku, vorikonazol će biti prisutan pri koncentraciji od 5 mg/ml do do 50 mg/ml, na primer, 10 mg/ml do 30 mg/ml. Ciklodekstrinski derivat formule I će da bude prisutan u molarnom odnosu vorikonazol:ciklodekstrinski derivat od 1:1 do 1:10, na primer 1:2 do 1:7, naročito 1:1 do 1:3. Formulacije mogu da budu liofilizirane (suvo-smrzavanje) radi magacioniranja pre korišćenja i dopunjene sa vodom kada je to potrebno.
U sledećem primeru, sulfobutiletar /3-ciklodekstrin ima prosečnu sulfobutiletarsku supstituciju od 6,5 po molekulu ciklodekstrina i svaka sulfobutiletarska jedinica je prisutna u obliku svoje natrijumske soli.
Primer 1
I. v. formulacija vorikonazola
Postupak
1. Uz neprekidno mešanje doda se sulfobutiletar β-dekstrin (SBECD) u 80% konačne zapremine vode za injekcije i nastavi da se mesa dok se sav SBECD ne rastvori.
2. Doda se vorikonazol i rastvori se uz mešanje.
3. Zapremina rastvora se dopuni do konačne zapremine sa vodom za
injekcije.
4. Dobiveni rastvor se profiltrira kroz sterilni 0,2 mm najlonski filter u sterilni kontejner.
5. 20 ml rastvora se unese u sterilne smrzavanjem osušene ampule koje se zatim zatvore i tada se liofilizira.
Claims (7)
1. Farmaceutska formulacija naznačen time što obuhvata vorikonazol ili njegov farmaceutski prihvatljiv derivat i ciklodekstrinski derivat formule I: gde R1a-g, R2a-g i R3a-g svaki nezavisno predstavlja OH ili O(CH2)4S03H; uz predpostavku da bar jedan od R1 a - g predstvalja O(CH2)4 S03H; ili njegovu farmaceutski prihvatljivu so.
2. Farmaceutska formulacija prema zahtevu l, naznačena time što prosečan broj O(CH2)4S03H grupa po molukulu formule I je u oblasti 6,1 do 6,9.
3. Farmaceutska formulacija prema zahtevu l ili prema zahtevu 2, naznačena time što svaka O(CH2)4 S03H grupa je prisutna u obliku soli alkalnog metala .
4. Formulacija prema nekom od predhodnih zahteva naznačen time što je podešena z.a parenteralno primenu.
5. Formulacija prema nekom od pred hodnih zahteva naznačena time što ciklodekslrinski derivat formule T je prisutan u molarnom odnosu vorikonazol :ciklodekstrinski derivat od 1:1 do 1:10.
6. Formulacija prema nekom od predhodnih zahteva naznačena time što je rastvor u vodi .
7. Formulacija prema nekom od zahteva 1-5, naznačena time što je liofilizirana .
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9713149.4A GB9713149D0 (en) | 1997-06-21 | 1997-06-21 | Pharmaceutical formulations |
| PCT/EP1998/003477 WO1998058677A1 (en) | 1997-06-21 | 1998-06-02 | Pharmaceutical formulations containing voriconazole |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ME00907B true ME00907B (me) | 2007-08-03 |
Family
ID=10814734
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MEP-1999-681A ME00907B (me) | 1997-06-21 | 1998-06-02 | Farmaceutske formulacije koje sadrže vorikonazol |
Country Status (47)
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9818258D0 (en) * | 1998-08-21 | 1998-10-14 | Pfizer Ltd | Antifungal compositions |
| PE20020300A1 (es) | 2000-08-22 | 2002-05-10 | Pharmacia Corp | Composicion de solucion de un farmaco antibiotico a base de oxazolidinona con mejoramiento de la carga de farmaco |
| PE20020578A1 (es) | 2000-10-10 | 2002-08-14 | Upjohn Co | Una composicion de antibiotico topico para el tratamiento de infecciones oculares |
| ATE428423T1 (de) * | 2002-08-20 | 2009-05-15 | Bristol Myers Squibb Co | Aripiprazol-komplex-formulierung und verfahren |
| GB0327390D0 (en) * | 2003-11-25 | 2003-12-31 | Pfizer Ltd | Pharmaceutical formulations |
| WO2005055952A2 (en) * | 2003-12-08 | 2005-06-23 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Synergistic anti-cancer compositions |
| CA2572223C (en) | 2004-06-25 | 2014-08-12 | The Johns Hopkins University | Angiogenesis inhibitors |
| US20100204178A1 (en) | 2006-10-02 | 2010-08-12 | James Cloyd | Novel parenteral carbamazepine formulation |
| US20070082870A1 (en) * | 2005-10-11 | 2007-04-12 | Buchanan Charles M | Pharmaceutical formulations of cyclodextrins and antifungal azole compounds |
| AR061889A1 (es) | 2006-07-13 | 2008-10-01 | Medichem Sa | Proceso mejorado para la preparacion de voriconazol |
| CN1919846B (zh) * | 2006-09-14 | 2013-01-02 | 大道隆达（北京）医药科技发展有限公司 | 伏立康唑及其药用盐、中间体的一种新定向合成制备方法 |
| BG1110U1 (bg) * | 2007-06-19 | 2008-09-30 | Рудолф ПОДЛИПСКИ | Отоплителен съд за експресно локално загряване навода |
| EP2018866A1 (en) * | 2007-07-27 | 2009-01-28 | Sandoz AG | Pharmaceutical compositions containing voriconazole |
| US8192721B2 (en) * | 2007-12-13 | 2012-06-05 | Verrow Pharmaceuticals, Inc. | Compositions useful for reducing toxicity associated with gadolinium-based contrast agents |
| US20110224232A1 (en) * | 2008-05-06 | 2011-09-15 | Board Of Regents, The University Of Texas System | Treatment of Pulmonary Fungal Infection With Voriconazole via Inhalation |
| RU2472510C2 (ru) * | 2008-06-06 | 2013-01-20 | Гленмарк Фармасьютикалс Лимитед | Стабильная лекарственная форма для местного применения, содержащая вориконазол |
| CN101390825B (zh) * | 2008-10-01 | 2010-12-29 | 山东省眼科研究所 | 一种伏立康唑眼内释药系统 |
| EP3090737A1 (en) | 2008-10-21 | 2016-11-09 | Onyx Therapeutics, Inc. | Combination therapy with peptide epoxyketones |
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| CN103690968A (zh) * | 2013-11-21 | 2014-04-02 | 石药集团中奇制药技术（石家庄）有限公司 | 一种伏立康唑组合物及其制备方法 |
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| DE3346123A1 (de) | 1983-12-21 | 1985-06-27 | Janssen Pharmaceutica, N.V., Beerse | Pharmazeutische praeparate von in wasser schwerloeslichen oder instabilen arzneistoffen und verfahren zu ihrer herstellung |
| DE3347421A1 (de) | 1983-12-29 | 1985-07-11 | Hoechst Ag, 6230 Frankfurt | Verfahren zur herstellung von fluorarmen alkaliphosphatloesungen |
| GB8819308D0 (en) * | 1988-08-13 | 1988-09-14 | Pfizer Ltd | Triazole antifungal agents |
| KR0166088B1 (ko) * | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
| US5376645A (en) * | 1990-01-23 | 1994-12-27 | University Of Kansas | Derivatives of cyclodextrins exhibiting enhanced aqueous solubility and the use thereof |
| GB9002375D0 (en) * | 1990-02-02 | 1990-04-04 | Pfizer Ltd | Triazole antifungal agents |
| US5278175A (en) * | 1990-02-02 | 1994-01-11 | Pfizer Inc. | Triazole antifungal agents |
| GB9512961D0 (en) * | 1995-06-26 | 1995-08-30 | Pfizer Ltd | Antifungal agents |
| GB9602080D0 (en) | 1996-02-02 | 1996-04-03 | Pfizer Ltd | Pharmaceutical compounds |
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