ES2576740T3 - Composiciones farmacéuticas tópicas que incluyen REL-N-[6-[(2R,6S)-2,6-dimetil-4-morfolinil]-3-piridinil]-2-metil-4'-(trifluorometoxi)-[1,1'-bifenil]-3-carboxamida - Google Patents
Composiciones farmacéuticas tópicas que incluyen REL-N-[6-[(2R,6S)-2,6-dimetil-4-morfolinil]-3-piridinil]-2-metil-4'-(trifluorometoxi)-[1,1'-bifenil]-3-carboxamida Download PDFInfo
- Publication number
- ES2576740T3 ES2576740T3 ES10733012.8T ES10733012T ES2576740T3 ES 2576740 T3 ES2576740 T3 ES 2576740T3 ES 10733012 T ES10733012 T ES 10733012T ES 2576740 T3 ES2576740 T3 ES 2576740T3
- Authority
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- Prior art keywords
- biphenyl
- methyl
- dimethyl
- carboxamide
- trifluoromethoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 239000012049 topical pharmaceutical composition Substances 0.000 title abstract description 6
- VZZJRYRQSPEMTK-CALCHBBNSA-N sonidegib Chemical compound C1[C@@H](C)O[C@@H](C)CN1C(N=C1)=CC=C1NC(=O)C1=CC=CC(C=2C=CC(OC(F)(F)F)=CC=2)=C1C VZZJRYRQSPEMTK-CALCHBBNSA-N 0.000 title description 3
- MEJYDZQQVZJMPP-ULAWRXDQSA-N (3s,3ar,6r,6ar)-3,6-dimethoxy-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan Chemical compound CO[C@H]1CO[C@@H]2[C@H](OC)CO[C@@H]21 MEJYDZQQVZJMPP-ULAWRXDQSA-N 0.000 abstract 2
- 239000002904 solvent Substances 0.000 abstract 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 abstract 1
- 239000003963 antioxidant agent Substances 0.000 abstract 1
- 239000003623 enhancer Substances 0.000 abstract 1
- 239000003349 gelling agent Substances 0.000 abstract 1
- 239000004094 surface-active agent Substances 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 11
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 7
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 6
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 6
- 239000006071 cream Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 229960004217 benzyl alcohol Drugs 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 229960000541 cetyl alcohol Drugs 0.000 description 3
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 3
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 3
- UFIYKNIUNRVRSI-UHFFFAOYSA-N hexadecyl octadecyl sulfate;sodium Chemical compound [Na].CCCCCCCCCCCCCCCCCCOS(=O)(=O)OCCCCCCCCCCCCCCCC UFIYKNIUNRVRSI-UHFFFAOYSA-N 0.000 description 3
- 229940057917 medium chain triglycerides Drugs 0.000 description 3
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- HRUXPZHTFRRWJA-UHFFFAOYSA-N 3-phenyl-2-(trifluoromethoxy)benzamide Chemical compound NC(=O)C1=CC=CC(C=2C=CC=CC=2)=C1OC(F)(F)F HRUXPZHTFRRWJA-UHFFFAOYSA-N 0.000 description 1
- VLPBNQMPKNGOJC-DTORHVGOSA-N 6-[(2r,6s)-2,6-dimethylmorpholin-4-yl]pyridin-3-amine Chemical compound C1[C@@H](C)O[C@@H](C)CN1C1=CC=C(N)C=N1 VLPBNQMPKNGOJC-DTORHVGOSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 102100032373 Coiled-coil domain-containing protein 85B Human genes 0.000 description 1
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 description 1
- 101000868814 Homo sapiens Coiled-coil domain-containing protein 85B Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-PWCQTSIFSA-N Tritiated water Chemical compound [3H]O[3H] XLYOFNOQVPJJNP-PWCQTSIFSA-N 0.000 description 1
- -1 [6- (cis-2,6-dimethylmorpholin-4-yl) -pyridin-3-yl] -amide -biphenyl-3-carboxylic acid Chemical compound 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- LVTYICIALWPMFW-UHFFFAOYSA-N diisopropanolamine Chemical compound CC(O)CNCC(C)O LVTYICIALWPMFW-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000009459 hedgehog signaling Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- 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
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/08—Antiseborrheics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
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- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Dermatology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Composición farmacéutica tópica, la cual incluye: a) N-(6-[(25,6R)-2,6-dimetilmorfolino)piridin-3-il]-2-metil-4'-(trifluorometoxi)-bifenil-3-carboxamida;**Fórmula** b) uno o más solventes; c) opcionalmente una fase oleosa; d) opcionalmente uno o más antioxidantes; e) opcionalmente uno o más mejoradores de consistencia; f) opcionalmente uno o más tensoactivos; g) opcionalmente uno o más conservadores; y h) opcionalmente uno o más agentes gelificantes. en donde el uno o más solventes incluyen dimetil isosorbida (DMI).
Description
Composiciones farmacéuticas tópicas que incluyen REL-N-[6-[(2R,6S)-2,6-dimetil-4-morfolinil]-3-piridinil]-2-metil-4’
(trifluorometoxi)-[1,1’-bifenil]-3-carboxamida.
Campo de la invención
5 La presente invención se refiere a composiciones farmacéuticas de la [6-(cis-2,6-dimetil-morfolin-4-il)-piridin-3-il]-amida del ácido 2-metil-4’-trifluoro-metoxi-bifenil-3-carboxílico, al uso de estas composiciones en aplicaciones terapéuticas, y a métodos para la elaboración de estas composiciones. La invención se refiere además a una forma específica de la [6(cis-2,6-dimetil-morfolin-4-il)-piridin-3-il]-amida del ácido 2-metil-4’-trifluoro-metoxi-bifenil-3-carboxílico, y a la elaboración y uso de esta forma.
10 Antecedentes de la invención
Las Publicaciones Internacionales Números WO 2007/131201 y WO 2008/154259 dan a conocer compuestos con actividad como moduladores de la senda de señalización de hedgehog, incluyendo la [6-(cis-2,6-dimetil-morfolin-4-il)piridin-3-il]-amida del ácido 2-metil-4’-trifluoro-metoxi-bifenil-3-carboxílico. No se dan a conocer específicamente las composiciones farmacéuticas tópicas.
15 Breve descripción de la invención
Existe una necesidad de proporcionar una composición farmacéutica tópica que comprenda a la [6-(cis-2,6-dimetilmorfolin-4-il)-piridin-3-il]-amida del ácido 2-metil-4’-trifluoro-metoxi-bifenil-3-carboxílico, el cual tiene propiedades convenientes, tales como una penetración óptima del compuesto activo en la piel, una exposición sistémica limitada, una buena estabilidad y/o aceptación por parte del paciente. Por consiguiente, es un objeto general de la invención
20 proporcionar composiciones que posean tales propiedades deseables, y estos objetivos se logran mediante la provisión de una composición como se define en las reivindicaciones.
La invención proporciona, en su sentido más amplio, una composición farmacéutica tópica que incluye al compuesto de la [6-(cis-2,6-dimetil-morfolin-4-il)-piridin-3-il]-amida del ácido 2-metil-4’-trifluoro-metoxi-bifenil-3-carboxílico:
25 o un solvato del mismo (“agente de la invención”), y uno o más excipientes. El agente de la invención también se identifica de una manera alternativa mediante el nombre: rel-N-[6-[(2R,6S)-2,6-dimetil-4-morfolinil]-3-piridinil]-2-metil-4’(trifluoro-metoxi)-[1,1’-bifenil]-3-carboxamida o N-(6-((2S,6R)-2,6-dimetil-morfolino)-piridin-3-il)-2-metil-4’-(trifluorometoxi)-bifenil-3-carboxamida. Para evitar dudas, los nombres químicos anteriormente mencionados se refieren todos al mismo compuesto químico denotado mediante la estructura química anterior, y se pueden utilizar indistintamente.
2
- Formulación XD (tipo de solución en crema)
- Excipiente
- Cantidad [%]
- Cetil-estearil-sulfato de sodio
- 1
- Alcohol cetílico
- 4
- Alcohol estearílico
- 4
- Monoestearato de glicerol
- 2
- Alcohol bencílico
- 5
- Polisorbato 80
- 2
- Agua
- 61.5
- Formulación XF (tipo de solución en crema)
- Excipiente
- Cantidad [%]
- Compuesto activo*
- 0.4
- Triglicéridos de cadena mediana (MCT)
- 20
- DIPA
- 15
- Transcutol
- 10
- Cetil-estearil-sulfato de sodio
- 1
- Alcohol cetílico
- 4
- Alcohol estearílico
- 4
- Monoestearato de glicerol
- 2
- Alcohol bencílico
- 1
- Hidroxi-tolueno butilado
- 0.1
11
- Formulación XD (tipo de solución en crema)
- Excipiente
- Cantidad [%]
- Agua
- 42.5
- Formulación XH (tipo de solución en crema)
- Sustancia
- Cantidad [g]
- Triglicéridos de cadena mediana
- 5
- Adipato de di-isopropilo
- 15
- Propilenglicol
- 10
- Alcohol oleílico
- 10
- Cetil-estearil-sulfato de sodio
- 1
- Alcohol cetílico
- 4
- Alcohol estearílico
- 4
- Monoestearato de glicerol
- 2
- Alcohol bencílico
- 3
- BHT
- 0.1
- BHA
- 0.1
- Compuesto activo*
- 0.5
- Agua
- 45.3
- * “Compuesto activo” significa la [6-(cis-2,6-dimetil-morfolin-4-il)-piridin-3-il]-amida del ácido 2-metil-4’trifluoro-metoxi-bifenil-3-carboxílico.
Ensayo de penetración/permeación en piel humana in vitro
Aproximadamente. 300 miligramos ó 300 microlitros de la formulación se aplicaron a cada pedazo de piel (muestras descongeladas de piel abdominal de cadáver humano dermatomizada hasta un grosor de 500 micras). La integridad de la piel se determinó mediante la evaluación de la permeación de agua tritiada. Las formulaciones se probaron en muestras de piel que tenían una permeación de 3H2O similar. La cámara receptora se llenó con una mezcla de suero regulado con fosfato y suero bovino fetal (2+1, volumen/volumen; pH = 7.4) como la solución receptora (Gibco BRL, CH) para simular las condiciones fisiológicas humanas y la remoción sistémica del fármaco a partir de la piel. La solución
12
Claims (1)
-
imagen1 imagen2 imagen3 FIG. 1imagen4 FIG. 218
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US295884P | 2001-06-05 | ||
| US22714109P | 2009-07-21 | 2009-07-21 | |
| US227141P | 2009-07-21 | ||
| US29588410P | 2010-01-18 | 2010-01-18 | |
| PCT/EP2010/060470 WO2011009852A2 (en) | 2009-07-21 | 2010-07-20 | Pharmaceutical compositions |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2576740T3 true ES2576740T3 (es) | 2016-07-11 |
Family
ID=42633096
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10733012.8T Active ES2576740T3 (es) | 2009-07-21 | 2010-07-20 | Composiciones farmacéuticas tópicas que incluyen REL-N-[6-[(2R,6S)-2,6-dimetil-4-morfolinil]-3-piridinil]-2-metil-4'-(trifluorometoxi)-[1,1'-bifenil]-3-carboxamida |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US8722672B2 (es) |
| EP (1) | EP2456422B1 (es) |
| JP (2) | JP6106434B2 (es) |
| KR (1) | KR101732751B1 (es) |
| CN (2) | CN103893184B (es) |
| AR (1) | AR077490A1 (es) |
| AU (1) | AU2010275240A1 (es) |
| BR (1) | BR112012001340B1 (es) |
| CA (1) | CA2768457C (es) |
| ES (1) | ES2576740T3 (es) |
| HK (1) | HK1199217A1 (es) |
| IN (1) | IN2012DN00239A (es) |
| MX (1) | MX2012000954A (es) |
| RU (1) | RU2589699C2 (es) |
| TW (1) | TW201107314A (es) |
| WO (1) | WO2011009852A2 (es) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI433674B (zh) | 2006-12-28 | 2014-04-11 | Infinity Discovery Inc | 環杷明（ｃｙｃｌｏｐａｍｉｎｅ）類似物類 |
| JP2014516549A (ja) * | 2011-06-02 | 2014-07-17 | ノバルティス アーゲー | ヘッジホッグ阻害剤療法のためのバイオマーカー |
| CO6910042A1 (es) | 2011-09-28 | 2014-03-31 | Titan Wood Ltd | Paneles de fibras de densidad media |
| AU2014220339B2 (en) * | 2013-02-25 | 2016-12-01 | Sun Pharmaceutical Industries Limited | Oral formulation and suspension of an oncology drug |
| CN105906616B (zh) * | 2015-03-30 | 2018-09-04 | 苏州晶云药物科技有限公司 | Lde225单磷酸盐的晶型及其制备方法 |
| CA2988289C (en) | 2015-06-04 | 2023-12-05 | PellePharm, Inc. | Topical formulations for delivery of hedgehog inhibitor compounds and use thereof |
| CN105330658B (zh) * | 2015-12-09 | 2017-09-19 | 苏州明锐医药科技有限公司 | 索尼吉布的制备方法 |
| CN112773805B (zh) * | 2019-11-11 | 2024-05-10 | 中国科学院脑科学与智能技术卓越创新中心 | 缺血性脑损伤的新型治疗药物 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4082881A (en) * | 1976-12-23 | 1978-04-04 | E. R. Squibb & Sons, Inc. | Topical and other type pharmaceutical formulations containing isosorbide carrier |
| US5216011A (en) * | 1989-09-01 | 1993-06-01 | Bristol-Myers Squibb Co. | Stable solutions of mitomycin c |
| IT1265001B1 (it) * | 1993-12-16 | 1996-10-17 | Zambon Spa | Composizione farmaceutica per uso topico contenente acido (s)-2-(4- isobutilfenil) propionico |
| DE4405898A1 (de) * | 1994-02-18 | 1995-08-24 | Schering Ag | Transdermale therapeutische Systeme enthaltend Sexualsteroide |
| FR2719475B1 (fr) * | 1994-05-05 | 1996-06-07 | Oreal | Composition cosmétique et/ou dermatologique à gélifiant polymérique cationique, ses utilisations notamment pour la dépigmentation de la peau. |
| US6765001B2 (en) * | 2001-12-21 | 2004-07-20 | Medicis Pharmaceutical Corporation | Compositions and methods for enhancing corticosteroid delivery |
| WO2004078163A2 (en) | 2003-02-28 | 2004-09-16 | Transform Pharmaceuticals, Inc. | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
| RU2207124C1 (ru) * | 2002-04-24 | 2003-06-27 | Закрытое акционерное общество "Брынцалов-А" | Крем "брамизил" противогрибкового действия |
| DE102006014454B3 (de) | 2006-03-29 | 2007-11-08 | Hoffmann, Frank | Stanzvorrichtung mit Zuführeinrichtung |
| UA93548C2 (uk) | 2006-05-05 | 2011-02-25 | Айерем Елелсі | Сполуки та композиції як модулятори хеджхогівського сигнального шляху |
| BR122021010386B1 (pt) * | 2007-06-07 | 2021-08-03 | Sun Pharma Global Fze | Uso de n-(6-((2r,6s)-2,6-dimetilmorfolino)piridin-3-il)-2-metil-4'-(trifluorometoxi) bifenil-3- carboxamida como moduladores da rota de hedgehog |
| CN101445508B (zh) * | 2008-11-21 | 2011-08-31 | 南京威尔化工有限公司 | 异山梨醇二甲醚的合成方法 |
-
2010
- 2010-07-19 AR ARP100102630A patent/AR077490A1/es unknown
- 2010-07-20 MX MX2012000954A patent/MX2012000954A/es active IP Right Grant
- 2010-07-20 CN CN201410074829.6A patent/CN103893184B/zh active Active
- 2010-07-20 US US13/386,125 patent/US8722672B2/en active Active
- 2010-07-20 CN CN2010800321676A patent/CN102481249A/zh active Pending
- 2010-07-20 ES ES10733012.8T patent/ES2576740T3/es active Active
- 2010-07-20 JP JP2012521016A patent/JP6106434B2/ja active Active
- 2010-07-20 BR BR112012001340-8A patent/BR112012001340B1/pt active IP Right Grant
- 2010-07-20 IN IN239DEN2012 patent/IN2012DN00239A/en unknown
- 2010-07-20 RU RU2012105752/15A patent/RU2589699C2/ru not_active Application Discontinuation
- 2010-07-20 EP EP10733012.8A patent/EP2456422B1/en active Active
- 2010-07-20 CA CA2768457A patent/CA2768457C/en active Active
- 2010-07-20 KR KR1020127004353A patent/KR101732751B1/ko active Active
- 2010-07-20 AU AU2010275240A patent/AU2010275240A1/en not_active Abandoned
- 2010-07-20 TW TW099123860A patent/TW201107314A/zh unknown
- 2010-07-20 WO PCT/EP2010/060470 patent/WO2011009852A2/en not_active Ceased
-
2014
- 2014-12-23 HK HK14112855.3A patent/HK1199217A1/xx unknown
-
2015
- 2015-06-10 JP JP2015117478A patent/JP2015199753A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| TW201107314A (en) | 2011-03-01 |
| RU2012105752A (ru) | 2013-08-27 |
| CN103893184A (zh) | 2014-07-02 |
| RU2589699C2 (ru) | 2016-07-10 |
| HK1199217A1 (en) | 2015-06-26 |
| KR101732751B1 (ko) | 2017-05-04 |
| KR20120097482A (ko) | 2012-09-04 |
| CA2768457A1 (en) | 2011-01-27 |
| US20120122866A1 (en) | 2012-05-17 |
| EP2456422A2 (en) | 2012-05-30 |
| AR077490A1 (es) | 2011-08-31 |
| BR112012001340B1 (pt) | 2021-08-03 |
| CN103893184B (zh) | 2016-03-02 |
| WO2011009852A3 (en) | 2012-01-19 |
| JP6106434B2 (ja) | 2017-03-29 |
| JP2012533598A (ja) | 2012-12-27 |
| CN102481249A (zh) | 2012-05-30 |
| US8722672B2 (en) | 2014-05-13 |
| CA2768457C (en) | 2018-01-23 |
| IN2012DN00239A (es) | 2015-05-01 |
| JP2015199753A (ja) | 2015-11-12 |
| BR112012001340A2 (pt) | 2016-03-15 |
| EP2456422B1 (en) | 2016-03-16 |
| AU2010275240A1 (en) | 2012-02-02 |
| MX2012000954A (es) | 2012-02-28 |
| WO2011009852A2 (en) | 2011-01-27 |
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