ES2536235T3 - Dispositivo polimérico de liberación prolongada - Google Patents
Dispositivo polimérico de liberación prolongada Download PDFInfo
- Publication number
- ES2536235T3 ES2536235T3 ES11180259.1T ES11180259T ES2536235T3 ES 2536235 T3 ES2536235 T3 ES 2536235T3 ES 11180259 T ES11180259 T ES 11180259T ES 2536235 T3 ES2536235 T3 ES 2536235T3
- Authority
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- Prior art keywords
- sucrose
- composition
- oil
- mecl2
- formulations
- 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.)
- Expired - Lifetime
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- 238000013265 extended release Methods 0.000 title 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 abstract description 27
- 239000000203 mixture Substances 0.000 abstract description 21
- 229930006000 Sucrose Natural products 0.000 abstract description 20
- 239000005720 sucrose Substances 0.000 abstract description 20
- 239000011148 porous material Substances 0.000 abstract description 12
- 108010011459 Exenatide Proteins 0.000 abstract description 5
- JUFFVKRROAPVBI-PVOYSMBESA-N chembl1210015 Chemical group C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N[C@H]1[C@@H]([C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@]3(O[C@@H](C[C@H](O)[C@H](O)CO)[C@H](NC(C)=O)[C@@H](O)C3)C(O)=O)O2)O)[C@@H](CO)O1)NC(C)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 JUFFVKRROAPVBI-PVOYSMBESA-N 0.000 abstract description 5
- 229960001519 exenatide Drugs 0.000 abstract description 5
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 abstract description 3
- 229910052753 mercury Inorganic materials 0.000 abstract description 3
- 230000001687 destabilization Effects 0.000 abstract description 2
- 238000002459 porosimetry Methods 0.000 abstract description 2
- 229920001184 polypeptide Polymers 0.000 abstract 3
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 3
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 3
- 150000003839 salts Chemical class 0.000 abstract 2
- 229920000249 biocompatible polymer Polymers 0.000 abstract 1
- 239000000872 buffer Substances 0.000 abstract 1
- 230000002035 prolonged effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
- 238000009472 formulation Methods 0.000 description 15
- 238000000338 in vitro Methods 0.000 description 8
- 239000011859 microparticle Substances 0.000 description 7
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 6
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 6
- 235000011130 ammonium sulphate Nutrition 0.000 description 6
- 229920002545 silicone oil Polymers 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000009849 deactivation Effects 0.000 description 2
- 0 CC(C)C(C)C(C)(*1)C(*IC)C1[C@]1C2(C)[C@](C)CS*12 Chemical compound CC(C)C(C)C(C)(*1)C(*IC)C1[C@]1C2(C)[C@](C)CS*12 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229940090181 propyl acetate Drugs 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K9/20—Pills, tablets, discs, rods
-
- 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
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/2278—Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- 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
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- 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
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5089—Processes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Vascular Medicine (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Inorganic Chemistry (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Fats And Perfumes (AREA)
- Silicon Polymers (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Vending Machines For Individual Products (AREA)
- Lubricants (AREA)
- Ceramic Products (AREA)
Abstract
Una composición para la liberación prolongada de un polipéptido biológicamente activo, que comprende un polímero biocompatible que tiene el polipéptido biológicamente activo dispersado en él de modo que esté presente de un 3% (p/p) a un 10% (p/p) del peso de la composición y sacarosa dispersada en él de modo que esté presente en un 2% (p/p) del peso de la composición, donde el polipéptido biológicamente activo es exendina-4, donde el volumen de poro total de la composición es de 0.1 mL/g o menos según se determina utilizando porosimetría por intrusión de mercurio y donde la composición está exenta de tampones y de sales de desestabilización salina.
Description
E11180259
04-05-2015
donde:
D = diámetro del poro γ = tensión superficial (constante) θ = ángulo de contacto (constante)
5 P = presión
Por lo tanto, el tamaño del poro en el cual se introducirá el mercurio es inversamente proporcional a la presión aplicada. Asumiendo que todos los poros son cilindros rígidos, el diámetro del poro promedio (D=4V/A) se puede calcular dividiendo el volumen del poro (V=πD2h/4) por el área del poro (A=πDh).
DISOLVENTES RESIDUALES
10 Se utilizó un único método para la cuantificación de heptano, etanol y diclorometano. El equipo estuvo constituido por un cromatógrafo de gases HP 5890 Serie 2 con una columna Rtx 1301, 30 cm x 0.53 mm. Se disolvieron aproximadamente 130 mg de micropartículas en 10 mL de N,N-dimetilformamida. Se utilizó acetato de propilo como patrón interno. Se ajustó la preparación de la muestra de modo que se pudieran cuantificar concentraciones de diclorometano de tan solo un 0.03%.
Se prepararon los lotes de micropartículas expuestos en la Tabla 1 según se ha descrito anteriormente a una escala de 100 gramos utilizando el polímero 4A y una relación de aceite de silicona respecto al diclorometano de 1.5:1 o de
1:1 y el aceite de silicona tuvo una viscosidad de 350 cs. La cantidad de exendina-4 y los excipientes utilizados en la formulación también se exponen en la Tabla 1.
20 TABLA 1
- Lote n.º
- Formulación Liberación brusca in vitro (%) Observaciones
- 02-019-147(n.º 1)
- 0% de sacarosa, 0% de SA 0.40 1.5:1 Aceite de Si: MeCl2
- 02-019-167(n.º 2)
- 2% de sacarosa (F16) 0.40 1.5:1 Aceite de Si: MeCl2
- 02-019-160(n.º 2.1)
- 2% de sacarosa (F16) 0.44 1.5:1 Aceite de Si l: MeCl2
- 02-019-164(n.º 2-2)
- 2% de sacarosa (F16) 0.45 1.5:1 Aceite de Si: MeCl2
- 02-030-08(n.º 2-3)
- 2% de sacarosa (F16) 0.80 1:1 Aceite de Si: MeCl2
- 02-030-01(n.º 2-4)
- 2% de sacarosa (F16) 1.0 1:1 Aceite de Si: MeCl2
- 02-030-04(n.º 2-5)
- 2% de sacarosa (F16) 1.1 1:1 Aceite de Si: MeCl2
- 02-019-136(n.º 3-1)
- 2% de sacarosa, 0.5% de SA (F14) 1.3 50:50 Desactivación
- 02-019-115(n.º 3-2)
- 2% de sacarosa, 0.5% de SA (F14) 2.2 1.5:1 Aceite de Si: MeCl2
- 02-019-170(n.º 4)
- 0% de sacarosa, 0.5% de SA 3.8 1.5:1 Aceite de Si: MeCl2
- 02-019-133A(n.º 3-3)
- 2% de sacarosa, 0.5% de SA (F14) 12.7 100% Desactivación con heptano
- 02-019-185(n.º 5) (5% de adición del fármaco)
- 2% de sacarosa (F17) 0.5 5% de adición del fármaco, 1.5:1 Aceite de Si: MeCl2
- 02-019-64 (n.º 3-4)
- 2% de sacarosa, 0.5% de SA (F14) 0.5 1.5:1 Aceite de Si: MeCl2
- 02-019-10(n.º 3-5)
- 2% de sacarosa, 0.5% de SA (F14) 1.30 1:1 Aceite de Si: MeCl2
- 02-001-196(n.º 3-6)
- 2% de sacarosa, 0.5% de SA (F14) 2.70 1:1 Aceite de Si: MeCl2
- 02-019-24(n.º 3-7)
- 2% de sacarosa, 0.5% de SA (F14) 6.70 1:1 Aceite de Si: MeCl2
- *TODAS LAS FORMULACIONES TUVIERON UNA ADICIÓN DEL FÁRMACO DE UN 3% CON LA EXCEPCIÓN
12
E11180259
04-05-2015
- Lote n.º
- Formulación Liberación brusca in vitro (%) Observaciones
- DE LA POROSIDAD N.º 5
El volumen de intrusión total obtenido de la porosimetría por intrusión de mercurio y los diámetros de poro promedio calculados se proporcionan en la TABLA 2. La relación entre el diámetro de poro promedio y la liberación in vitro se muestra en la FIG. 1.
TABLA 2
- Lot n.º
- Volumen del Poro Total (mL/g) Liberación brusca in vitro (%) Diámetro del poro promedio (µm)
- 02-019-147(n.º 1)
- 0.033 0.40 0.0068
- 02-019-167(n.º 2)
- 0.035 0.40 0.0069
- 02-019-160(n.º 2-1)
- 0.037 0.44 0.0070
- 02-019-164(n.º 2-2)
- 0.035 0.45 0.0070
- 02-030-08(n.º 2-3)
- 0.036 0.80 0.0070
- 02-030-01 (n.º 2-4)
- 0.038 1.0 0.0073
- 02-030-04(n.º 2-5)
- 0.039 1.1 0.0074
- 02-019-136(n.º 3-1)
- 0.041 1.3 0.0073
- 02-019-115(n.º 3-2)
- 0.039 2.2 0.0078
- 02-019-170(n.º 4)
- 0.067 3.8 0.0125
- 02-019-133A(n.º 33)
- 0.513 12.7 0.0277
- 02-019-64 (n.º 3-4)
- 0.030 0.5 0.0060
- 02-019-10(n.º 3-5)
- 0.060 1.30 0.0090
- 02-001-196(n.º 3-6)
- 0.060 2.70 0.0100
- 02-019-24(n.º 3-7)
- 0.180 6.70 0.0170
La FIG. 1 muestra el efecto del sulfato de amonio en la liberación inicial in vitro. Los datos indican que la liberación inicial in vitro se correlaciona con el diámetro del poro de las micropartículas. Las formulaciones hechas con sulfato de amonio mostraron niveles variables de liberación in vitro y una porosidad variable a diferencia de las 10 formulaciones sin sulfato de amonio que exhibieron una porosidad y liberación constantes. Durante la fabricación de micropartículas, la presencia de sulfato de amonio en la fase acuosa puede provocar la desestabilización salina de la sustancia farmacológica durante la preparación de la emulsión interna. Las diferencias en el microentorno de los precipitados pueden contribuir a las diferencias en la porosidad y, por lo tanto, la variación en la liberación inicial. El efecto no se observó en formulaciones preparadas sin sulfato de amonio. Las formulaciones con sacarosa y
15 exendina-4 muestran un nivel de liberación inicial más deseable y constante en comparación con formulaciones que tienen exendina-4, sacarosa y sulfato de amonio.
La FIG. 2 demuestra además el efecto de la porosidad en la liberación in vitro y el impacto que las condiciones del procesamiento, concretamente la relación del aceite de silicona respecto al diclorometano, tiene en la porosidad de las micropartículas formadas. Resumiendo, las formulaciones de micropartículas preparadas utilizando una relación
20 del aceite de silicona respecto al diclorometano de 1:1 (Formulaciones 2-4 y 2-5 de la Tabla 1) tienen una liberación inicial más elevada que las mismas formulaciones preparadas utilizando una relación del aceite de silicona respecto al diclorometano de 1.5:1 (Formulaciones 2, 2-1 y 2-2 de la Tabla 1). La FIG. 2 sugiere que una relación más elevada del aceite de silicona respecto al diclorometano conlleva una porosidad menor lo que conlleva una liberación inicial menor.
Se llevaron a cabo análisis por SEM criogénica tal y como se ha descrito anteriormente con las Formulaciones de los tipos 2, 3 y 5 de la Tabla 1. Las FIGS. 3A-3B son barridos de micrografías para formulaciones seleccionadas de tipo 2 (Formulación 2-2, FIG. 3A) y de tipo 5 (5% de exendina-4, 2% de sacarosa, FIG. 3B). Las FIGS. 4A-D son barridos
13
Claims (1)
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/US2004/011547 WO2005110425A1 (en) | 2004-04-15 | 2004-04-15 | Polymer-based sustained release device |
EP20110180259 EP2409707B8 (en) | 2004-04-15 | 2004-04-15 | Polymer-based sustained release device |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2536235T3 true ES2536235T3 (es) | 2015-05-21 |
Family
ID=35393985
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES04750134T Expired - Lifetime ES2375802T3 (es) | 2004-04-15 | 2004-04-15 | Dispositivo de liberación sostenida a base de pol�?mero. |
ES11180259.1T Expired - Lifetime ES2536235T3 (es) | 2004-04-15 | 2004-04-15 | Dispositivo polimérico de liberación prolongada |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES04750134T Expired - Lifetime ES2375802T3 (es) | 2004-04-15 | 2004-04-15 | Dispositivo de liberación sostenida a base de pol�?mero. |
Country Status (25)
Country | Link |
---|---|
US (7) | US8617613B2 (es) |
EP (2) | EP2409707B8 (es) |
JP (1) | JP5030292B2 (es) |
KR (2) | KR101040415B1 (es) |
CN (1) | CN1968700A (es) |
AT (1) | ATE531374T1 (es) |
AU (1) | AU2004319756C1 (es) |
BR (1) | BRPI0418702A (es) |
CA (1) | CA2560981C (es) |
CY (2) | CY2012010I2 (es) |
DE (1) | DE122012000028I1 (es) |
DK (1) | DK1734971T3 (es) |
EA (1) | EA200601904A1 (es) |
ES (2) | ES2375802T3 (es) |
FR (1) | FR12C0029I1 (es) |
HK (2) | HK1099693A1 (es) |
HR (2) | HRP20110831T1 (es) |
IL (1) | IL178589A0 (es) |
LU (1) | LU91989I2 (es) |
MX (1) | MXPA06011924A (es) |
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PT (2) | PT1734971E (es) |
SI (1) | SI2409707T1 (es) |
WO (1) | WO2005110425A1 (es) |
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- 2004-04-15 WO PCT/US2004/011547 patent/WO2005110425A1/en active Application Filing
- 2004-04-15 JP JP2007508312A patent/JP5030292B2/ja not_active Expired - Lifetime
- 2004-04-15 BR BRPI0418702-4A patent/BRPI0418702A/pt not_active IP Right Cessation
- 2004-04-15 MX MXPA06011924A patent/MXPA06011924A/es active IP Right Grant
- 2004-04-15 KR KR1020107026352A patent/KR20100129799A/ko not_active Application Discontinuation
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2006
- 2006-09-14 US US11/521,091 patent/US7563871B2/en not_active Expired - Lifetime
- 2006-10-15 IL IL178589A patent/IL178589A0/en unknown
- 2006-11-14 NO NO20065217A patent/NO20065217L/no not_active Application Discontinuation
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2007
- 2007-06-22 HK HK07106714.5A patent/HK1099693A1/xx not_active IP Right Cessation
- 2007-07-20 US US11/878,160 patent/US20080119569A1/en not_active Abandoned
- 2007-07-20 US US11/878,159 patent/US20080125351A1/en not_active Abandoned
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2009
- 2009-06-12 US US12/483,871 patent/US20090247463A1/en not_active Abandoned
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2011
- 2011-11-11 HR HR20110831T patent/HRP20110831T1/hr unknown
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2012
- 2012-04-26 CY CY2012010C patent/CY2012010I2/el unknown
- 2012-04-27 FR FR12C0029C patent/FR12C0029I1/fr active Active
- 2012-04-30 DE DE201212000028 patent/DE122012000028I1/de active Pending
- 2012-04-30 LU LU91989C patent/LU91989I2/fr unknown
- 2012-07-24 HK HK12107269.5A patent/HK1166606A1/xx not_active IP Right Cessation
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2013
- 2013-01-16 US US13/743,117 patent/US9238076B2/en active Active
- 2013-11-22 US US14/087,132 patent/US8877252B2/en not_active Expired - Lifetime
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2015
- 2015-03-10 HR HRP20150272TT patent/HRP20150272T1/hr unknown
- 2015-04-23 CY CY20151100373T patent/CY1116337T1/el unknown
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