ES2527622T3 - Formulación de galio para el tratamiento y la prevención de enfermedades infecciosas - Google Patents
Formulación de galio para el tratamiento y la prevención de enfermedades infecciosas Download PDFInfo
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- ES2527622T3 ES2527622T3 ES10797479.2T ES10797479T ES2527622T3 ES 2527622 T3 ES2527622 T3 ES 2527622T3 ES 10797479 T ES10797479 T ES 10797479T ES 2527622 T3 ES2527622 T3 ES 2527622T3
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- gallium
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- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 title abstract description 29
- 229910052733 gallium Inorganic materials 0.000 title abstract description 28
- 239000000203 mixture Substances 0.000 title description 17
- 238000009472 formulation Methods 0.000 title description 12
- 208000035473 Communicable disease Diseases 0.000 title 1
- 230000002265 prevention Effects 0.000 title 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 abstract description 14
- 239000000843 powder Substances 0.000 abstract description 4
- 230000000845 anti-microbial effect Effects 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 4
- 229910002651 NO3 Inorganic materials 0.000 description 4
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 4
- CHPZKNULDCNCBW-UHFFFAOYSA-N gallium nitrate Chemical compound [Ga+3].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O CHPZKNULDCNCBW-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 4
- 239000001509 sodium citrate Substances 0.000 description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- ROHFNLRQFUQHCH-RXMQYKEDSA-N D-leucine Chemical compound CC(C)C[C@@H](N)C(O)=O ROHFNLRQFUQHCH-RXMQYKEDSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 229940044658 gallium nitrate Drugs 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 229960000999 sodium citrate dihydrate Drugs 0.000 description 2
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 2
- KSFOVUSSGSKXFI-GAQDCDSVSA-N CC1=C/2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(C=C)=C5C)C(C=C)=C4C)C(C)=C3CCC(O)=O)=C1CCC(O)=O Chemical class CC1=C/2NC(\C=C3/N=C(/C=C4\N\C(=C/C5=N/C(=C\2)/C(C=C)=C5C)C(C=C)=C4C)C(C)=C3CCC(O)=O)=C1CCC(O)=O KSFOVUSSGSKXFI-GAQDCDSVSA-N 0.000 description 1
- 239000004395 L-leucine Substances 0.000 description 1
- 235000019454 L-leucine Nutrition 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229960003136 leucine Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
-
- 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
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—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
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A61P31/10—Antimycotics
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- 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
- A61P31/12—Antivirals
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
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- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
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- Communicable Diseases (AREA)
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- Otolaryngology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
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- Inorganic Chemistry (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Una formulación farmacéutica que comprende una solución, o un polvo seco obtenido de dicha solución, de una concentración antimicrobiana eficaz de galio (III) y citrato, en la que la relación molar del citrato con respecto al galio es de 1,25:1 a 4:1.
Description
E10797479
09-01-2015
Farmacocinética in vivo del galio administrado en el pulmón
5 Se ensayó el tiempo de residencia de las formulaciones de galio en aerosol en ratas adultas Sprague-Dawley por vía intratraqueal (i.t.) directa. Se administró una formulación comparable por vía intravenosa como control. La solución de galio formulada administrada i.t. presentó un tiempo de residencia significativamente más largo en el pulmón que la administración por vía i.v. (Figura 10).
La Tabla 13 describe las relaciones molares de algunas de las formulaciones de la presente invención. Dichas formulaciones no son limitantes. Las formulaciones 45, 49 y 50 no contienen galio. Las formulaciones 44 y 48 contienen galio en una sal de protoporfirina (de mayor peso molecular que el nitrato), por lo tanto, la relación del
15 manitol y citrato con respecto al galio es sesgada para dichas composiciones.
- Tabla 13. Relaciones molares de los componentes de las formulaciones de galio
- Nº
- Ga Citrato Manitol Leu Leu3 D-leu iso-leu EtOH % (v/v)
- 1
- 1,0 1,0
- 2
- 1,0 0,7 0,5
- 3
- 1,0 0,7 0,6 0,1
- 4
- 1,0 0,7 0,6 1,0
- 5
- 1,0 0,7 0,6 2,2
- 6
- 1,0 0,7 0,6 0,5
- 7
- 1,0 0,7 2,2
- 8
- 1,0 0,6 2,2
- 9
- 1,0 0,6 0,5
- 10
- 1,0 1,4
- 11
- 1,0 2,7 2,1 8,8
- 12
- 1,0 2,7 2,1 2,4
- 13
- 1,0 0,7 0,6 0,2
- 14
- 1,0 2,7 2,1 0,8
- 15
- 1,0 2,2
- 16
- 1,0 0,5
- 17
- 1,0 9,3
- 18
- 1,0 0,7 0,5
- 19
- 1,0 0,7 0,6 0,3
- 20
- 1,0 0,7 0,6 0,1
- 21
- 1,0 0,7 0,5
- 22
- 1,0 1,0 0,6 0,5
- 23
- 1,0 1,0 0,5
- 24
- 1,0 0,5
- 25
- 1,0 2,7 2,1 2,4
- 26
- 1,0 0,7 0,5
- 27
- 1,0 1,0 0,6 0,5
25
E10797479
09-01-2015
- Tabla 13. Relaciones molares de los componentes de las formulaciones de galio
- Nº
- Ga Citrato Manitol Leu Leu3 D-leu iso-leu EtOH % (v/v)
- 28
- 1,0 0,5
- 29
- 1,0 1,0 0,6 0,5
- 30
- 1,0 1,0
- 30
- 31
- 1,0 1,0 50
- 32
- 1,0 1,0 0,5 10
- 33
- 1,0 1,0 0,5 30
- 34
- 1,0 1,0 0,5 50
- 35
- 1,0 1,0 0,02 0,6 10
- 36
- 1,0 1,0 0,02 0,6 30
- 37
- 1,0 1,0 0,02 0,6 50
- 38
- 1,0 1,0 0,1 0,6 10
- 39
- 1,0 1,0 0,1 0,6 30
- 40
- 1,0 1,0 0,1 0,6 50
- 41
- 1,0 1,0 0,6 0,6 10
- 42
- 1,0 1,0 0,6 0,6 50
- 43
- 1,0 1,0 1,9
- PPX de Ga
- 44 1,0 36,1 69,2
- Sin galio
- 45
- 46
- 1,0 1,0 0,1
- 47
- 1,0 1,0 0,1 0,1
- 48
- 1,0 36,1 69,2
- Sin galio
- 49
- Sin galio
- 50
Efecto de las relaciones del citrato con respecto al galio en la solubilidad
5 Lo siguiente se refiere a la preparación de diversas realizaciones de la formulación de la presente invención que se usarán para la administración en aerosol. Para determinar la solubilidad de las mezclas de galio y citrato, se variaron la concentración del galio, la proporción del citrato con respecto al galio y el pH de la solución. Se mezcló nitrato de galio 58,7 mM con cantidades apropiadas de citrato de sodio, obteniéndose las relaciones que se muestran en la
10 Tabla 14 que se presenta a continuación. Al añadirse, el citrato de sodio era citrato de sodio dihidratado sólido (cristalino o en polvo). La mezcla se realizó mediante agitación manual en un tubo de ensayo, facilitándose la disolución mediante el calentamiento en un baño de agua caliente, donde el baño se mantuvo a aproximadamente 60-80 ºC. Se ajustó el pH a los valores indicados (pH 3, 7 o 10) usando NaOH o HCl. La solubilidad de la mezcla se determinó visualmente, es decir, por la falta de precipitado. El término "precipitado" engloba bien que el nitrato de
15 galio y el citrato de sodio nunca se disuelven por completo en solución, o que el nitrato de galio y el citrato de sodio se disuelven completamente, pero con la formación de un precipitado al dejar que la mezcla alcance la temperatura ambiente. Para ajustar el pH, se añadió NaOH 10 N inicialmente controlando el pH. A medida que el pH se acercaba al pH deseado, se añadió NaOH 1 N, en lugar de NaOH 10 N. Aunque el tiempo hasta la evaluación de la precipitación no es relevante, se esperaron aproximadamente 48 horas hasta la evaluación de la precipitación con el
20 fin de garantizar la estabilidad de la solución durante largos períodos de tiempo.
A la concentración de galio dada, cualquier relación molar del citrato con respecto al galio superior o igual a 1:1 resultó en una mezcla soluble para los intervalos de pH estudiados de la solución. En ausencia de citrato, sin
26
E10797479
09-01-2015
En otro aspecto, se pueden realizar los ensayos anteriores, donde la concentración de galio es de 234,6 mM, 117,3 mM, 58,65 mM, 29,3 mM o 14,6 mM, y así sucesivamente, y las formulaciones, las soluciones y los métodos relacionados se pueden basar en relaciones de citrato:galio que no produzcan precipitación. En otro aspecto, se puede usar un anión o agente complejante distinto del citrato, pudiéndose preparar las formulaciones, las soluciones y los métodos apropiados de la presente invención.
- Tabla 15
- Citrato/Galio (relación molar)
- pH ¿Precipitado?
- 0
- 3 Sí
- 0
- 7 Sí
- 0
- 10 Sí
- 1
- 3 No
- 1
- 7 No
- 1
- 10 Sí
- 1,5
- 3 No
- 1,5
- 7 No
- 1,5
- 10 Sí
- 2
- 3 No
- 2
- 7 No
- 2
- 10 No
- 3
- 3
- Sí
- 3
- 7 No
- 3
- 10 No
- Galio a 469,2 mM
- 1
- 3 Sí
- 1
- 7 No
- 1
- 10 (No ensayado porque se encontró precipitado con 234,6 mM)
- 1,5
- 3 No
- 1,5
- 7 No
- 1,5
- 10 (No ensayado porque se encontró precipitado con 234,6 mM)
- 2
- 3 No
- 2
- 7 No
- 2
- 10 Sí
10 Preparación de galio en polvo seco usando el método de secado por pulverización
Se disolvió Ga(NO3)3 �9H2O, obteniéndose Ga(NO3)3 58,7 mM. Se añadió citrato de sodio dihidratado a la solución de galio en una cantidad correspondiente a las relaciones molares del citrato con respecto al galio de 1:1, 2:1 y 3:1
15 (Tabla 16). A la solución, se añadió L-leucina 30,5 Mm, y se ajustó el pH de la solución a 7. Se secó la solución por pulverización a Tint/Text = 80/60 ºC, q = 0,5 ml/min y Patm = 24 psi. El polvo se recogió en condiciones de temperatura y humedad controladas de 30 ºC y HR < 5 %, respectivamente. Se encapsularon 50 mg del polvo en el interior de una cápsula de tipo 2 y se ensayaron en cuanto a la distribución del tamaño de partícula usando un impactador de cascada Andersen (ACI) dotado de Turbospin® a un caudal de 28 l/min. Se determinaron la FPD<3,3 �m, la FPD<4,7 �m
28
Claims (1)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US17545709P | 2009-05-04 | 2009-05-04 | |
| US175457P | 2009-05-04 | ||
| PCT/US2010/033599 WO2011005354A2 (en) | 2009-05-04 | 2010-05-04 | Gallium formulation for the treatment and prevention of infectious diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2527622T3 true ES2527622T3 (es) | 2015-01-27 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10797479.2T Active ES2527622T3 (es) | 2009-05-04 | 2010-05-04 | Formulación de galio para el tratamiento y la prevención de enfermedades infecciosas |
Country Status (4)
| Country | Link |
|---|---|
| US (2) | US9539233B2 (es) |
| EP (1) | EP2427061B1 (es) |
| ES (1) | ES2527622T3 (es) |
| WO (1) | WO2011005354A2 (es) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101801521B (zh) | 2007-05-14 | 2015-06-17 | 纽约州立大学研究基金会 | 生物膜中细菌细胞内的生理学分散响应诱导 |
| US9539233B2 (en) | 2009-05-04 | 2017-01-10 | Aridis Pharmaceuticals Inc. | Gallium formulation for the treatment and prevention of infectious diseases |
| US20130310307A1 (en) * | 2012-04-26 | 2013-11-21 | Los Angeles Biomedical Research Institute At Harbor-Ucla Medical Center | Methods and compositions for treatment of multidrug-resistant bacterial and fungal infections |
| WO2014193868A1 (en) | 2013-05-29 | 2014-12-04 | Aguas De Manizales S.A. E.S.P. | Compositions for water treatment and methods of using thereof |
| EP3217992A4 (en) * | 2014-11-10 | 2018-07-18 | National Institutes Of Health | Probiotic therapeutic applications |
| AR103173A1 (es) | 2014-12-22 | 2017-04-19 | Novarits Ag | Productos farmacéuticos y composiciones líquidas estables de anticuerpos il-17 |
| IL308091B1 (en) | 2016-09-13 | 2026-01-01 | Allergan Inc | Protein-free stabilized Clostridium toxin preparations |
| DE102016222256A1 (de) | 2016-11-14 | 2018-05-17 | BSH Hausgeräte GmbH | Haushaltsgerät mit Projektionsvorrichtung und Verfahren zu seinem Betrieb |
| EP3565848A4 (en) | 2017-01-03 | 2020-09-02 | The University of North Carolina at Chapel Hill | NITRIC OXIDE RELEASING ALGINATES AS BIODEGRADABLE ANTIBACTERIAL SCAFFOLDS AND RELATED PROCESSES |
| US10537661B2 (en) | 2017-03-28 | 2020-01-21 | DePuy Synthes Products, Inc. | Orthopedic implant having a crystalline calcium phosphate coating and methods for making the same |
| US10537658B2 (en) | 2017-03-28 | 2020-01-21 | DePuy Synthes Products, Inc. | Orthopedic implant having a crystalline gallium-containing hydroxyapatite coating and methods for making the same |
| WO2018178902A1 (en) | 2017-03-28 | 2018-10-04 | The University Of North Carolina At Chapel Hill | Nitric oxide-releasing polyaminoglycosides as biodegradable antibacterial scaffolds and methods pertaining thereto |
| CA3082130A1 (en) | 2017-11-15 | 2019-05-23 | The University Of North Carolina At Chapel Hill | Nitric oxide-releasing hyperbranched compounds as antibacterial scaffolds and methods pertaining thereto |
| CN111836648A (zh) | 2018-03-06 | 2020-10-27 | 北卡罗来纳大学查佩尔希尔分校 | 作为可生物降解抗菌支架的一氧化氮释放型环糊精以及其相关方法 |
| US11541105B2 (en) | 2018-06-01 | 2023-01-03 | The Research Foundation For The State University Of New York | Compositions and methods for disrupting biofilm formation and maintenance |
| AU2019414421B2 (en) | 2018-12-28 | 2023-08-31 | The University Of North Carolina At Chapel Hill | Nitric oxide-releasing antibacterial polymers and scaffolds fabricated therefrom and methods pertaining thereto |
| CN116473073A (zh) * | 2023-05-08 | 2023-07-25 | 广东方中高新材料有限公司 | 一种含镓配合物的吡唑醚菌酯增效悬浮制剂及其制备方法 |
| WO2026022256A1 (en) * | 2024-07-24 | 2026-01-29 | Institut National de la Santé et de la Recherche Médicale | Gallium-apramycin complexes, methods of preparation thereof and their use in the treatment of bacterial infections |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1219210A (en) | 1982-10-22 | 1987-03-17 | Warrell Raymond P., Jr. | Use of gallium salts to treat disorders of calcium homeostasis |
| US4659568A (en) | 1985-02-27 | 1987-04-21 | American Cyanamid Company | Process for solubilization, purification and characterization of protein from insoluble protein aggregates or complexes and compositions of matter therefrom |
| US4704277A (en) | 1985-04-30 | 1987-11-03 | Sloan-Kettering Institute For Cancer Research | Methods of treating bone disorders |
| US5686116A (en) | 1990-01-12 | 1997-11-11 | New York Society For The Relief Of The Ruptured And Crippled, Maintaining The Hospital For Special Surgery | Methods of enhancing repair, healing and augmentation of bone implants |
| US5556645A (en) | 1990-01-12 | 1996-09-17 | Bockman; Richard | Methods of enhancing wound healing and tissue repair |
| US5196412A (en) | 1991-03-06 | 1993-03-23 | Johnson Matthey, Inc. | Gallium compounds |
| GB9111689D0 (en) | 1991-05-31 | 1991-07-24 | Johnson Matthey Plc | Gallium compounds |
| US5700487A (en) | 1996-03-04 | 1997-12-23 | The Ohio State University | Treatment of pulmonary inflammation |
| US6203822B1 (en) | 1996-09-03 | 2001-03-20 | University Of Iowa Research Foundation | Gallium-containing compounds for the treatment of infections caused by intracellular pathogens and pathogens causing chronic pulmonary infection |
| US20020068761A1 (en) | 1999-10-04 | 2002-06-06 | Bernstein Lawrence R. | Gallium complexes of 3-hydroxy-4-pyrones to treat mycobacterial infections |
| CN1188111C (zh) * | 1999-10-29 | 2005-02-09 | 耐科塔医药公司 | 分散性得到改进的干粉组合物 |
| US20070231406A1 (en) * | 2006-01-30 | 2007-10-04 | Bucalo Louis R | Use of gallium to treat biofilm-associated infections |
| CA2682745C (en) | 2007-04-02 | 2014-12-23 | Sideromics, Llc | Methods for preventing or treating infectious diseases caused by extracellular microorganisms, including antimicrobial-resistant strains thereof, using gallium compounds |
| US20090275655A1 (en) | 2008-04-30 | 2009-11-05 | Genta Incorporated | Pharmaceutical Gallium Compositions and Methods |
| US9539233B2 (en) | 2009-05-04 | 2017-01-10 | Aridis Pharmaceuticals Inc. | Gallium formulation for the treatment and prevention of infectious diseases |
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- 2010-05-04 WO PCT/US2010/033599 patent/WO2011005354A2/en not_active Ceased
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| US20120148635A1 (en) | 2012-06-14 |
| EP2427061B1 (en) | 2014-12-03 |
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| WO2011005354A2 (en) | 2011-01-13 |
| EP2427061A4 (en) | 2012-12-05 |
| US8637090B2 (en) | 2014-01-28 |
| WO2011005354A3 (en) | 2011-04-28 |
| US20120128729A1 (en) | 2012-05-24 |
| US9539233B2 (en) | 2017-01-10 |
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