ES2562059T3 - Inhibidor de acción rápida de la secreción de ácido gástrico - Google Patents
Inhibidor de acción rápida de la secreción de ácido gástrico Download PDFInfo
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- ES2562059T3 ES2562059T3 ES07716990.2T ES07716990T ES2562059T3 ES 2562059 T3 ES2562059 T3 ES 2562059T3 ES 07716990 T ES07716990 T ES 07716990T ES 2562059 T3 ES2562059 T3 ES 2562059T3
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- acid secretion
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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
- A61K31/315—Zinc compounds
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
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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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
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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
- A61K31/65—Tetracyclines
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- 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
- A61K33/30—Zinc; Compounds thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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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
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
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Abstract
Una composición farmacéutica para la administración al estómago de un paciente que comprende una cantidad eficaz de al menos una sal de cinc farmacéuticamente aceptable en combinación con un inhibidor de la bomba de protones, opcionalmente en combinación con un vehículo, aditivo o excipiente farmacéuticamente aceptable para su uso para incrementar rápidamente el pH de los jugos gástricos en el estómago de un paciente con dicha necesidad hasta al menos 3,0 dentro de un periodo no superior a una hora después de su administración.
Description
de Sigma y Molecular Probes.
Resultados
Localización inmunohistoquímica de la ATPasa H+, K+
5 La inmunohistoquímica usando anticuerpos específicos dirigidos contra epítopos muy conservados dentro de las subunidades α o β de la ATPasa H+, K+ gástrica identificó tinción específica para ambas subunidades en las glándulas fúndicas (figura 7 A).
Microscopía electrónica
Después de la obtención de secciones en Epon de unión gastroesofágica de rata en ayunas, se realizó la microscopía electrónica sobre las glándulas gástricas que venían justo después de esta unión, y estas se llamaron F1 y se usaron en todos nuestros experimentos. Las figuras 7B, C muestran la localización de la etiqueta de oro de
15 la ATPasa H+, K+ en la célula parietal de la glándula fúndica. Percibimos una mayor densidad de tinción sobre el polo apical de la célula en los canalículos secretores o vacuolares. Esto podría correlacionarse con la alta extrusión basal de protones de las regiones del fondo en comparación con el cuerpo, debido al hecho de que la proteína está siempre en la membrana en la glándula fúndica, mientras que en el cuerpo el receptor está dentro del canalículo secretor hasta la estimulación.
Tinción del receptor de H2
La tinción del receptor de H2 se hizo tanto en el fondo como en el cuerpo para examinar la presencia y densidad del receptor en ambas áreas del estómago. Encontramos una clara tinción basolateral en las glándulas del cuerpo y no
25 pudimos detectar tinción en las glándulas fúndicas. Estos resultados se correlacionan con la falta de efecto de la histamina en la estimulación de la secreción de ácido en el fondo. Se vio claramente que el receptor H2 está ausente en las glándulas del fondo y presente en el cuerpo (datos no mostrados).
Secreción de ácido inducida por secretagogo
El pH intracelular se midió usando el colorante BCECF sensible a pH y se verificó continuamente usando un sistema de toma de imágenes de fluorescencia en tiempo real para identificar los cambios en el pH intracelular. Los índices de salida de protones se calcularon como ΔpHi/min usando una técnica que se desarrolló en nuestro laboratorio para las glándulas del cuerpo21a-25a. Medimos el cambio en el índice de salida en presencia y ausencia de secretagogos.
35
Efecto de la histamina sobre la ATPasa H+, K+ del fondo y del cuerpo
Incubamos glándulas individuales con histamina 100 µM durante 20 minutos. La histamina estuvo presente durante todo el protocolo de superfusión. En la glándula del cuerpo medimos una tasa de extrusión de protones estimulada por histamina de 0,056 0,008 ΔpHi/min, mientras que la secreción de ácido basal sin ningún secretagogo fue de 0,011 0,002 ΔpHi/min (figuras 8C, D). En comparación con el cuerpo, el fondo mostró un alto índice de extrusión de protones, incluso por debajo de las condiciones basales, (0,039 0,009 ΔpHi/ min). Éste es similar a la secreción de ácido inducida por histamina (0,040 0,0079 ΔpHi/min, figuras 8A, B). Estos datos muestran que no hay efecto de la histamina sobre las glándulas de la zona F1 en comparación con los controles.
45
Acetilcolina y secreción de ácido en el fondo
En la siguiente serie, investigamos las propiedades funcionales de las glándulas fúndicas de acuerdo con la estimulación neuronal por la vía de la ACh. Al contrario que con la histamina, hubo un cambio evidente en los índices de extrusión de protones después de la estimulación. Aunque los controles aún estaban bombeando hacia afuera protones de forma activa, las glándulas que se estimularon con acetilcolina 100 µM durante la carga de colorante y a lo largo de toda la perfusión. Determinamos que la acetilcolina causó un aumento del índice de alcalinización (0,075 0,0015 ΔpHi/min frente a los controles 0,039 0,009 ΔpHi/min), mostrando un efecto directo de la acetilcolina sobre la extrusión de ácido en el fondo (figura 9).
55
Efecto de la pentagastrina en la zona F1
Para determinar si la gastrina también podía activar la ATPasa H+,K+ del fondo, llevamos a cabo estudios usando pentagastrina, un péptido sintético que contiene los cinco aminoácidos terminales de la gastrina, el cual se sabe que causa una fuerte secreción de ácido en las glándulas del cuerpo. A una dosis de pentagastrina de 100 µM observamos índices de alcalinización que fueron de 0,062 0,007 ΔpHi/min, lo que fue similar a la acetilcolina en cuanto al aumento del índice de extrusión de protones desde las células del fondo (figura 9).
Inhibidores de la secreción de ácido gástrico
65 En la siguiente serie de estudios intentamos determinar si las glándulas fúndicas tenían perfiles de inhibición de la
17
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24a. Busque SM, Kerstetter JE, Geibel JP, Insogna K. L-type amino acids stimulate gastric acid secretion by activation of the calcium-sensing receptor in parietal cells. Am J Physiol Gastrointest Liver Physiol 2005;289:G664-G669.
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Claims (1)
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Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US76259506P | 2006-01-27 | 2006-01-27 | |
US762595P | 2006-01-27 | ||
US76483406P | 2006-02-03 | 2006-02-03 | |
US764834P | 2006-02-03 | ||
US85089106P | 2006-10-11 | 2006-10-11 | |
US850891P | 2006-10-11 | ||
PCT/US2007/001950 WO2007089511A2 (en) | 2006-01-27 | 2007-01-25 | Fast acting inhibitor of gastric acid secretion |
Publications (1)
Publication Number | Publication Date |
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ES2562059T3 true ES2562059T3 (es) | 2016-03-02 |
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ID=38327882
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Application Number | Title | Priority Date | Filing Date |
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ES07716990.2T Active ES2562059T3 (es) | 2006-01-27 | 2007-01-25 | Inhibidor de acción rápida de la secreción de ácido gástrico |
ES13193624.7T Active ES2609976T3 (es) | 2006-01-27 | 2007-01-25 | Combinación de sal de cinc y agente anti-H. pylori como inhibidor de acción rápida de la secreción de ácido gástrico |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
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ES13193624.7T Active ES2609976T3 (es) | 2006-01-27 | 2007-01-25 | Combinación de sal de cinc y agente anti-H. pylori como inhibidor de acción rápida de la secreción de ácido gástrico |
Country Status (15)
Country | Link |
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US (1) | US11510894B2 (es) |
EP (2) | EP2705845B1 (es) |
JP (3) | JP5469865B2 (es) |
CN (2) | CN103463096B (es) |
CA (1) | CA2635272C (es) |
DK (1) | DK1976532T3 (es) |
ES (2) | ES2562059T3 (es) |
HK (1) | HK1191861A1 (es) |
HR (1) | HRP20151437T1 (es) |
HU (1) | HUE029222T2 (es) |
PL (1) | PL1976532T3 (es) |
PT (1) | PT1976532E (es) |
RS (1) | RS54543B1 (es) |
SI (1) | SI1976532T1 (es) |
WO (1) | WO2007089511A2 (es) |
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US20060251722A1 (en) * | 2005-05-03 | 2006-11-09 | Novavax, Inc. | Multi-component vitamin and mineral supplement for the optimal absorption of components |
US8512761B2 (en) | 2006-01-27 | 2013-08-20 | Yale University | Fast acting inhibitor of gastric acid secretion |
DK1976532T3 (en) | 2006-01-27 | 2016-02-01 | Univ Yale | FAST-ACTING INHIBITOR of gastric acid secretion |
-
2007
- 2007-01-25 DK DK07716990.2T patent/DK1976532T3/en active
- 2007-01-25 CA CA2635272A patent/CA2635272C/en active Active
- 2007-01-25 ES ES07716990.2T patent/ES2562059T3/es active Active
- 2007-01-25 HU HUE07716990A patent/HUE029222T2/en unknown
- 2007-01-25 US US12/086,379 patent/US11510894B2/en active Active
- 2007-01-25 CN CN201310174056.4A patent/CN103463096B/zh not_active Expired - Fee Related
- 2007-01-25 PT PT77169902T patent/PT1976532E/pt unknown
- 2007-01-25 ES ES13193624.7T patent/ES2609976T3/es active Active
- 2007-01-25 WO PCT/US2007/001950 patent/WO2007089511A2/en active Application Filing
- 2007-01-25 SI SI200731736T patent/SI1976532T1/sl unknown
- 2007-01-25 EP EP13193624.7A patent/EP2705845B1/en active Active
- 2007-01-25 PL PL07716990T patent/PL1976532T3/pl unknown
- 2007-01-25 CN CN2007800036618A patent/CN101374526B/zh not_active Expired - Fee Related
- 2007-01-25 RS RS20160022A patent/RS54543B1/en unknown
- 2007-01-25 EP EP07716990.2A patent/EP1976532B1/en active Active
- 2007-01-25 JP JP2008552394A patent/JP5469865B2/ja not_active Expired - Fee Related
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2013
- 2013-08-12 JP JP2013167225A patent/JP2013241457A/ja active Pending
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2014
- 2014-05-30 HK HK14105100.0A patent/HK1191861A1/zh not_active IP Right Cessation
-
2015
- 2015-08-06 JP JP2015155729A patent/JP6366548B2/ja not_active Expired - Fee Related
- 2015-12-30 HR HRP20151437TT patent/HRP20151437T1/hr unknown
Also Published As
Publication number | Publication date |
---|---|
CN101374526B (zh) | 2013-08-07 |
WO2007089511A3 (en) | 2008-04-10 |
RS54543B1 (en) | 2016-06-30 |
DK1976532T3 (en) | 2016-02-01 |
EP1976532A2 (en) | 2008-10-08 |
EP1976532B1 (en) | 2015-11-11 |
EP2705845B1 (en) | 2016-10-05 |
WO2007089511A2 (en) | 2007-08-09 |
CA2635272C (en) | 2016-11-29 |
JP6366548B2 (ja) | 2018-08-01 |
PL1976532T3 (pl) | 2016-05-31 |
PT1976532E (pt) | 2016-02-11 |
JP2009524669A (ja) | 2009-07-02 |
US11510894B2 (en) | 2022-11-29 |
CN103463096B (zh) | 2016-03-16 |
JP2013241457A (ja) | 2013-12-05 |
JP2015232016A (ja) | 2015-12-24 |
HUE029222T2 (en) | 2017-02-28 |
JP5469865B2 (ja) | 2014-04-16 |
EP1976532A4 (en) | 2010-12-15 |
EP2705845A1 (en) | 2014-03-12 |
HRP20151437T1 (hr) | 2016-02-12 |
CA2635272A1 (en) | 2007-08-09 |
HK1191861A1 (zh) | 2014-08-08 |
CN103463096A (zh) | 2013-12-25 |
ES2609976T3 (es) | 2017-04-25 |
CN101374526A (zh) | 2009-02-25 |
SI1976532T1 (sl) | 2016-04-29 |
US20090035393A1 (en) | 2009-02-05 |
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