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
- Publication number
- 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
- Authority
- ES
- Spain
- Prior art keywords
- acid secretion
- gastric acid
- gastric
- fast
- glands
- 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.)
- Active
Links
- 230000027119 gastric acid secretion Effects 0.000 title description 3
- 239000003112 inhibitor Substances 0.000 title description 2
- 210000002784 stomach Anatomy 0.000 abstract description 3
- 239000000654 additive Substances 0.000 abstract 1
- 230000000996 additive effect Effects 0.000 abstract 1
- 239000003937 drug carrier Substances 0.000 abstract 1
- 210000004051 gastric juice Anatomy 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 239000000546 pharmaceutical excipient Substances 0.000 abstract 1
- 229940126409 proton pump inhibitor Drugs 0.000 abstract 1
- 239000000612 proton pump inhibitor Substances 0.000 abstract 1
- 150000003751 zinc Chemical class 0.000 abstract 1
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 16
- 210000004907 gland Anatomy 0.000 description 13
- 229960001340 histamine Drugs 0.000 description 8
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 6
- 229960004373 acetylcholine Drugs 0.000 description 6
- 238000001125 extrusion Methods 0.000 description 6
- 238000010186 staining Methods 0.000 description 6
- 108091006112 ATPases Proteins 0.000 description 5
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000009858 acid secretion Effects 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- 101150056637 Hrh2 gene Proteins 0.000 description 3
- 108010079943 Pentagastrin Proteins 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 210000001156 gastric mucosa Anatomy 0.000 description 3
- ANRIQLNBZQLTFV-DZUOILHNSA-N pentagastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1[C]2C=CC=CC2=NC=1)NC(=O)CCNC(=O)OC(C)(C)C)CCSC)C(N)=O)C1=CC=CC=C1 ANRIQLNBZQLTFV-DZUOILHNSA-N 0.000 description 3
- 229960000444 pentagastrin Drugs 0.000 description 3
- 230000000580 secretagogue effect Effects 0.000 description 3
- 102100021022 Gastrin Human genes 0.000 description 2
- 108010052343 Gastrins Proteins 0.000 description 2
- 150000001413 amino acids Chemical group 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)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](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 2
- 238000001493 electron microscopy Methods 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 210000001711 oxyntic cell Anatomy 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 102000013830 Calcium-Sensing Receptors Human genes 0.000 description 1
- 108010050543 Calcium-Sensing Receptors Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 210000003236 esophagogastric junction Anatomy 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 230000002055 immunohistochemical effect Effects 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000021962 pH elevation Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000005086 pumping Methods 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
- A61K31/28—Compounds containing heavy metals
- A61K31/315—Zinc compounds
-
- 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
-
- 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
-
- 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
-
- 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
-
- 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
-
- 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
-
- 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
-
- 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
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Inorganic Chemistry (AREA)
- Molecular Biology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
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
22a. Waisbren SJ, Geibel J, Boron WF, Modlin IM. Luminal perfusion of isolated gastric glands. Am J Physiol 1994;266:C1013-C1027.
23a. Waisbren SJ, Geibel JP, Modlin IM, Boron WF. Unusual permeability properties of gastric gland cells. 5 Nature 1994;368:332-335.
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.
10 25a. Geibel JP, Wagner CA, Caroppo R, Qureshi I, Gloeckner J, Manuelidis L, Kirchhoff P, Radebold K. The stomach divalent ion-sensing receptor scar is a modulator of gastric acid secretion. J Biol Chem 2001;276:3954939552.
15 26a. Sachs G, Scott D, Reuben M. Omeprazole and the gastric mucosa. Digestion 1990;47 Suppl 1:35-38.
27a. Sachs G, Wallmark B. The gastric H+,K+-ATPase: the site of action of omeprazole. Scand J Gastroenterol Suppl 1989;166:3-11.
20 28a. Alino SF, Garcia D, Uvnas-Moberg K. On the interaction between intragastric pH and electrical vagal stimulation in causing gastric acid secretion and intraluminal release of gastrin and somatostatin in anesthetized rats. Acta Physiol Scand 1983;117:491-495.
29a. Meulemans AL, Eelen JG, Schuurkes JA. NO mediates gastric relaxation after brief vagal stimulation in 25 anesthetized dogs. Am J Physiol 1995;269:G255-G261.
30a. Singh J. Prostaglandin release from rat stomach following vagal stimulation or administration of acetylcholine. Eur J Pharmacol 1980;65:39-48.
30 31a. Aarimaa M, Soderstrom KO, Kalimo H, Inberg M, Nevalainen T. Morphology and function of the parietal cells after proximal selective vagotomy in duodenal ulcer patients. Scand J Gastroenterol 1984;19:787-797.
32a. Amdrup E. The surgical treatment of duodenal ulcer. Schweiz Med Wochenschr 1979;109:583-585.
35 33a. Waisbren SJ, Modlin IM. The evolution of therapeutic vagotomy. Surg Gynecol Obstet 1990;170:261-272.
34a. Abelo A, Eriksson UG, Karlsson MO, Larsson H, Gabrielsson J. A turnover model of irreversible inhibition of gastric acid secretion by omeprazole in the dog. J Pharmacol Exp Ther 2000;295:662-669.
40 35a. Andersen JB, Andrade DV, Wang T. Effects of inhibition gastric acid secretion on arterial acid-base status during digestion in the toad Bufo marinus. Comp Biochem Physiol A Mol Integr Physiol 2003;135:425-433.
36a. Gedda K, Scott D, Besancon M, Lorentzon P, Sachs G. Turnover of the gastric H+,K(+)-adenosine triphosphatase alpha subunit and its effect on inhibition of rat gastric acid secretion. Gastroenterology 1995;109:113445 1141.
37a. Sachs G, Shin JM, Pratha V, Hogan D. Synthesis or rupture: duration of acid inhibition by proton pump inhibitors. Drugs Today (Barc) 2003;39 Suppl A:11-14.
50 38a. Shamburek RD, Schubert ML. Pharmacology of gastric acid inhibition. Baillieres Clin Gastroenterol 1993;7:23-54.
39a. Locke GR, III. Current medical management of gastroesophageal reflux disease. Thorac Surg Clin 2005;15:369-375. 55 40a. Geibel JP. Secretion and absorption by colonic crypts. Annu Rev Physiol 2005;67:471-490.
23
Claims (1)
-
imagen1
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 |
|---|---|
| ES2562059T3 true ES2562059T3 (es) | 2016-03-02 |
Family
ID=38327882
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| 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 |
| ES07716990.2T Active ES2562059T3 (es) | 2006-01-27 | 2007-01-25 | Inhibidor de acción rápida de la secreción de ácido gástrico |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| 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 (14)
| Country | Link |
|---|---|
| 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) | ES2609976T3 (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) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10348909A1 (de) | 2003-10-21 | 2005-06-02 | Siemens Ag | Ankopplungsstruktur für zylinderförmige Resonatoren |
| CN103463096B (zh) | 2006-01-27 | 2016-03-16 | 耶鲁大学 | 胃酸分泌的快速作用抑制剂 |
| US8512761B2 (en) * | 2006-01-27 | 2013-08-20 | Yale University | Fast acting inhibitor of gastric acid secretion |
| AU2009223851A1 (en) * | 2008-03-03 | 2009-09-17 | Amgen Inc. | Methods of treating hyperacidic disorders |
| JP2010184914A (ja) * | 2009-02-13 | 2010-08-26 | Bizen Chemical Co Ltd | プロトンポンプ阻害活性を有する組成物 |
| US20110038852A1 (en) * | 2009-06-10 | 2011-02-17 | 3-V Biosciences, Inc. | Antivirals that target transporters, carriers, and ion channels |
| AU2010313216A1 (en) * | 2009-11-01 | 2012-06-14 | Synthetic Biologics, Inc. | Gastroretentive oral high dose zinc preparations |
| KR101799304B1 (ko) | 2010-05-12 | 2017-11-20 | 렘펙스 파머수티클스 인코퍼레이티드 | 테트라사이클린 조성물 |
| US20140039004A1 (en) * | 2012-07-31 | 2014-02-06 | Ono Pharmaceutical Co., Ltd. | Method of treating of gastroesophageal reflux disease |
| WO2015153552A1 (en) * | 2014-03-31 | 2015-10-08 | Yale University | Fast acting inhibitor of gastric acid secretion with enhanced activity |
| CN105232506A (zh) * | 2015-11-04 | 2016-01-13 | 温州医科大学 | 丁酸及其盐在制备治疗或预防胃溃疡药物中的应用 |
| CN105769840B (zh) * | 2016-04-01 | 2018-06-29 | 温州医科大学 | 乙酸及其盐的应用 |
| RU2659955C1 (ru) * | 2017-10-26 | 2018-07-04 | Галина Ильхамовна Лукина | Способ диагностики высоких гастроэзофагеальных рефлюксов |
| WO2020131650A1 (en) * | 2018-12-20 | 2020-06-25 | Colgate-Palmolive Company | Oral care composition comprising zinc and an amino acid for treating symptoms of a gastric disorder in the oral cavity |
| CN111388436A (zh) * | 2020-04-20 | 2020-07-10 | 北京健讯医药科技有限公司 | 一种海藻酸钠咀嚼片及其制备方法 |
| CN114908314B (zh) * | 2022-05-16 | 2023-11-28 | 浙江飞剑工贸有限公司 | 一种能持久微量释放金属离子的抗菌涂层及其制备方法 |
| WO2025170033A1 (ja) * | 2024-02-09 | 2025-08-14 | 富士フイルム株式会社 | 抗胃壁細胞抗体測定用試薬、抗胃壁細胞抗体測定用キット、および試料中の抗胃壁細胞抗体を測定する方法 |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE393532B (sv) | 1974-05-02 | 1977-05-16 | Draco Ab | Sett att framstella en farmaceutisk zinkberedning for astadkommande av en smaklig, fordragbar, peroral zinklosning innehallande ett zinkkomplex |
| US4863741A (en) | 1985-03-25 | 1989-09-05 | Abbott Laboratories | Tablet composition for drug combinations |
| US4940556A (en) | 1986-01-30 | 1990-07-10 | Syntex (U.S.A.) Inc. | Method of preparing long acting formulation |
| DE3775880D1 (es) | 1986-09-18 | 1992-02-20 | London School Of Pharmacy Innovations Ltd., London, Gb | |
| JPH07116160B2 (ja) | 1987-08-10 | 1995-12-13 | 浜理薬品工業株式会社 | 結晶性ｌ−カルノシン亜鉛錯体およびその製造法 |
| US5202128A (en) | 1989-01-06 | 1993-04-13 | F. H. Faulding & Co. Limited | Sustained release pharmaceutical composition |
| AUPM456894A0 (en) * | 1994-03-18 | 1994-04-14 | Glyzinc Pharmaceuticals Limited | Treatment for gastric disorders |
| US5708017A (en) * | 1995-04-04 | 1998-01-13 | Merck & Co., Inc. | Stable, ready-to-use pharmaceutical paste composition containing proton pump inhibitors |
| SE9600070D0 (sv) * | 1996-01-08 | 1996-01-08 | Astra Ab | New oral pharmaceutical dosage forms |
| HU225329B1 (en) * | 1996-09-12 | 2006-09-28 | Richter Gedeon Vegyeszet | Use of zinc or cobalt hyaluronate associate for the manufacture of pharmaceutical compositions of antimicrobial activity |
| GB9621273D0 (en) | 1996-10-11 | 1996-11-27 | Cortecs Ltd | Therapeutic method |
| US20030068326A1 (en) | 1998-05-15 | 2003-04-10 | Aphton Corporation | Method for the treatment of gastroesophageal reflux disease |
| US7816403B2 (en) | 1998-09-08 | 2010-10-19 | University Of Utah Research Foundation | Method of inhibiting ATF/CREB and cancer cell growth and pharmaceutical compositions for same |
| US6166071A (en) | 2000-03-13 | 2000-12-26 | Albion International, Inc. | Zinc amino acid chelates having ligands comprised of glycine and a sulfur-containing amino acids |
| US6576634B1 (en) | 2000-07-07 | 2003-06-10 | N.V. Nutricia | Pharmaceutical or dietetic preparation for improvement of fertility and sperm quality |
| IL154144A0 (en) * | 2000-07-28 | 2003-07-31 | Immupharm Aps | Method of treating symptoms of common cold, allergic rhinitis and infections relating to the respiratory tract |
| US20020198165A1 (en) | 2000-08-01 | 2002-12-26 | Bratzler Robert L. | Nucleic acids for the prevention and treatment of gastric ulcers |
| WO2002026210A2 (en) * | 2000-09-29 | 2002-04-04 | Geneva Pharmaceuticals Inc. | Proton pump inhibitor formulation |
| EP1262172A1 (en) | 2001-05-25 | 2002-12-04 | Italmed S.N.C. Di Galli G. & Pacini G. | Liquid polymer composition for prevention and treatment of the oral cavity diseases |
| US7026298B2 (en) * | 2001-06-04 | 2006-04-11 | Abbott Laboratories | Oral rehydration compositions |
| FI20011403L (fi) * | 2001-06-29 | 2002-12-30 | Carbion Oy | Menetelmä ja koostumukset vatsan sairauksien hoitoon |
| US6596708B1 (en) * | 2001-09-07 | 2003-07-22 | Advanced Medical Instruments | Composition for the treatment and prevention of endothelial dysfunction |
| US6930099B2 (en) * | 2001-09-07 | 2005-08-16 | Advanced Medical Instruments | Composition for the treatment and prevention of endothelial dysfunction |
| US6632449B2 (en) * | 2001-11-20 | 2003-10-14 | The Procter & Gamble Co. | Compositions and kits comprising a defined boron compound and methods of their preparation |
| EP1480517A4 (en) | 2002-02-07 | 2007-08-22 | Univ Columbia | ZINC SALT COMPOSITIONS FOR PREVENTING MOLECULAR BREAST EXTRACTION THROUGH SPERMICIDES AND MICROBICIDES |
| WO2004073654A2 (en) * | 2003-02-20 | 2004-09-02 | Santarus, Inc. | A novel formulation, omeprazole antacid complex-immediate release for rapid and sustained supression of gastric acid |
| WO2004099182A1 (en) * | 2003-05-05 | 2004-11-18 | Ranbaxy Laboratories Limited | Zinc salt of (s)-omeprazole |
| US20060235053A1 (en) | 2003-05-06 | 2006-10-19 | Atlanta Pharma Ag | Agents for the treatment of lower abdominal disorders |
| US7871649B2 (en) * | 2003-07-17 | 2011-01-18 | The Trustees Of Columbia University In The City Of New York | Antimicrobial compositions containing synergistic combinations of quaternary ammonium compounds and essential oils and/or constituents thereof |
| SI1651217T1 (sl) | 2003-07-23 | 2008-08-31 | Nycomed Gmbh | Alkalne soli inhibitorjev protonske ÄŤrpalke |
| EP1686976A2 (en) * | 2003-11-05 | 2006-08-09 | Santarus, Inc. | Combination of proton pump inhibitor and sleep aid |
| US20050238731A1 (en) * | 2003-12-29 | 2005-10-27 | Stephen Holt | Composition and method for treating the effects of diseases and maladies of the upper digestive tract |
| CA2554271A1 (en) | 2004-02-10 | 2005-08-25 | Santarus, Inc. | Combination of proton pump inhibitor, buffering agent, and nonsteroidal anti-inflammatory agent |
| WO2006072054A1 (en) | 2004-12-30 | 2006-07-06 | Genzyme Corporation | Zinc-containing treatments for hyperphosphatemia |
| US20060160783A1 (en) | 2004-12-30 | 2006-07-20 | Transform Pharmaceuticals, Inc. | Novel omeprazole forms and related methods |
| CN100515491C (zh) | 2005-01-04 | 2009-07-22 | 健能隆医药技术（上海）有限公司 | 白介素-22的医药用途 |
| US20060230553A1 (en) * | 2005-04-14 | 2006-10-19 | Helmut Thullen | Process for tinting, dyeing or doping of moulded components made of transparent (co)polyamides in aqueous dye bath |
| US20060251722A1 (en) * | 2005-05-03 | 2006-11-09 | Novavax, Inc. | Multi-component vitamin and mineral supplement for the optimal absorption of components |
| CN103463096B (zh) | 2006-01-27 | 2016-03-16 | 耶鲁大学 | 胃酸分泌的快速作用抑制剂 |
| US8512761B2 (en) | 2006-01-27 | 2013-08-20 | Yale University | Fast acting inhibitor of gastric acid secretion |
-
2007
- 2007-01-25 CN CN201310174056.4A patent/CN103463096B/zh not_active Expired - Fee Related
- 2007-01-25 HR HRP20151437TT patent/HRP20151437T1/hr unknown
- 2007-01-25 RS RS20160022A patent/RS54543B1/sr unknown
- 2007-01-25 ES ES13193624.7T patent/ES2609976T3/es active Active
- 2007-01-25 HU HUE07716990A patent/HUE029222T2/en unknown
- 2007-01-25 PL PL07716990T patent/PL1976532T3/pl unknown
- 2007-01-25 EP EP13193624.7A patent/EP2705845B1/en active Active
- 2007-01-25 DK DK07716990.2T patent/DK1976532T3/en active
- 2007-01-25 US US12/086,379 patent/US11510894B2/en active Active
- 2007-01-25 WO PCT/US2007/001950 patent/WO2007089511A2/en not_active Ceased
- 2007-01-25 CA CA2635272A patent/CA2635272C/en active Active
- 2007-01-25 ES ES07716990.2T patent/ES2562059T3/es active Active
- 2007-01-25 EP EP07716990.2A patent/EP1976532B1/en active Active
- 2007-01-25 JP JP2008552394A patent/JP5469865B2/ja not_active Expired - Fee Related
- 2007-01-25 SI SI200731736T patent/SI1976532T1/sl unknown
- 2007-01-25 PT PT77169902T patent/PT1976532E/pt unknown
- 2007-01-25 CN CN2007800036618A patent/CN101374526B/zh not_active Expired - Fee Related
-
2013
- 2013-08-12 JP JP2013167225A patent/JP2013241457A/ja active Pending
-
2015
- 2015-08-06 JP JP2015155729A patent/JP6366548B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| EP1976532A4 (en) | 2010-12-15 |
| WO2007089511A2 (en) | 2007-08-09 |
| US11510894B2 (en) | 2022-11-29 |
| EP2705845B1 (en) | 2016-10-05 |
| SI1976532T1 (sl) | 2016-04-29 |
| US20090035393A1 (en) | 2009-02-05 |
| EP1976532A2 (en) | 2008-10-08 |
| EP2705845A1 (en) | 2014-03-12 |
| RS54543B1 (sr) | 2016-06-30 |
| HRP20151437T1 (hr) | 2016-02-12 |
| JP5469865B2 (ja) | 2014-04-16 |
| PT1976532E (pt) | 2016-02-11 |
| EP1976532B1 (en) | 2015-11-11 |
| CN101374526B (zh) | 2013-08-07 |
| HUE029222T2 (en) | 2017-02-28 |
| CN101374526A (zh) | 2009-02-25 |
| CN103463096A (zh) | 2013-12-25 |
| JP6366548B2 (ja) | 2018-08-01 |
| WO2007089511A3 (en) | 2008-04-10 |
| CA2635272A1 (en) | 2007-08-09 |
| JP2015232016A (ja) | 2015-12-24 |
| JP2013241457A (ja) | 2013-12-05 |
| PL1976532T3 (pl) | 2016-05-31 |
| HK1191861A1 (zh) | 2014-08-08 |
| ES2609976T3 (es) | 2017-04-25 |
| DK1976532T3 (en) | 2016-02-01 |
| CA2635272C (en) | 2016-11-29 |
| JP2009524669A (ja) | 2009-07-02 |
| CN103463096B (zh) | 2016-03-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2562059T3 (es) | Inhibidor de acción rápida de la secreción de ácido gástrico | |
| Legros et al. | Melatonin from cerebrospinal fluid but not from blood reaches sheep cerebral tissues under physiological conditions | |
| ES2941629T3 (es) | Ligandos del receptor de neurotensina | |
| Sjöblom et al. | Peripheral melatonin mediates neural stimulation of duodenal mucosal bicarbonate secretion | |
| Sababi et al. | Mucus and alkali secretion in the rat duodenum: effects of indomethacin, Nω-nitro-L-arginine, and luminal acid | |
| Huether et al. | Effect of continuous melatonin infusions on steady‐state plasma melatonin levels in rats under near physiological conditions | |
| Aihara et al. | Importance of Ca2+ in gastric epithelial restitution—new views revealed by real-time in vivo measurements | |
| Lerch et al. | Gallstone-related pathogenesis of acute pancreatitis | |
| Holm | Gastric mucosal blood flow and mucosal protection | |
| Chacko et al. | Carcinogenicity, perinatal carcinogenicity and teratogenicity of low dose metronidazole (MNZ) in Swiss mice | |
| Millan et al. | Evidence that μ-opioid receptors mediate midbrain “stimulation-produced analgesia” in the freely moving rat | |
| ES2403378T3 (es) | Estudios de imagen de células beta pancreáticas dirigidos basados en un mecanismo | |
| Konturek et al. | Effects of non-peptidal CCK receptor antagonist (L-364,718) on pancreatic responses to cholecystokinin, gastrin, bombesin, and meat feeding in dogs. | |
| Sheward et al. | Hypothalamic release of atrial natriuretic factor and β-endorphin into rat hypophysial portal plasma: relationship to oestrous cycle and effects of hypophysectomy | |
| Ongali et al. | Autoradiographic analysis of mouse brain kinin B1 and B2 receptors after closed head trauma and ability of Anatibant mesylate to cross the blood–brain barrier | |
| Caldara et al. | Effect of nifedipine on gastric acid secretion and gastrin release in healthy man | |
| Kihl et al. | Fat inhibition of gastric acid secretion in duodenal ulcer patients before and after proximal gastric vagotomy. | |
| Kovács et al. | Chronic administration of a new potent agonist of growth hormone-releasing hormone induces compensatory linear growth in growth hormone-deficient rats: mechanism of action | |
| Matsushita et al. | Inhibition of prolactin secretion by gastrin releasing peptide (GRP) in the rat | |
| Ross et al. | The effect of gastric antral stimulation upon the secretion of hepatic bile | |
| Whitehouse et al. | Prevention of the gastrotoxicity of aspirin and related drugs in rats by lithium salts and sodium thiocyanate | |
| Koch et al. | Attenuation of left ventricular dysfunction by an ACE inhibitor after myocardial infarction in a kininogen-deficient rat model. | |
| Elmèr et al. | Compensatory hypertrophy of the rat's submaxillary gland | |
| Jo et al. | Effect of medial amygdaloid stimulation on pancreatic exocrine secretion in anesthetized rats | |
| Grimm et al. | Influence of verapamil on gastric acid secretion and gastrin release in dogs |