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US 2019/0314355 A1Published application
Compositions and methods for treating, ameliorating and preventing h. pylori infections
AssigneeCentre for Digestive Diseases
InventorThomas Julius BORODY
Life of this patent
Estimating the term…
Abstract
Provided are methods for treating, ameliorating, reversing and/or preventing a Helicobacter pylori (H. pylori) infection in an individual in need thereof, comprising: administering to the individual in need thereof a therapeutic combination comprising: (a) a composition comprising or consisting of: vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™; and (b) an antimicrobial or antibiotic drug or composition.
Claims17
A method for treating, ameliorating, reversing and/or preventing, or acting as a prophylaxis, a Helicobacter pylori (H. pylori) infection in an individual in need thereof, comprising:
- administering to the individual in need thereof a therapeutic combination comprising:
- (A)
- (a) a composition comprising or consisting of:
- vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™;
- and
- (b) an antimicrobial or antibiotic drug or composition comprising or consisting of:
- (i)
- (1) an amoxicillin, administered to the individual in need thereof at a dose of between about 1 gram (g) to about 2 g twice daily (bid), optionally the amoxicillin is formulated as amoxicillin/ clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a clarithromycin, optionally BIAXIN™, administered to the individual in need thereof at a dose of between about 100 mg to about 2 g twice daily,
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is administered to the individual in need thereof at a dose of between 20 mg to about 50 mg twice daily (bid), or for about 25 mg or more twice daily (bid);
- (ii)
- (1) an amoxicillin, administered to the individual in need thereof at a dose of between about 500 gm to about 1 g three times daily (tid), and optionally the amoxicillin is formulated as amoxicillin/ clavulanic acid, al so known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a metronidazole, optionally FLAGYL™, METRO™, administered to the individual in need thereof at a dose of between about 200 mg to about 500 mg three times daily (tid),
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is administered to the individual in need thereof at a dose of between 20 mg to about 50 mg three times daily (tid), or for about 25 mg or more three times daily (tid);
- (iii)
- (1) an amoxicillin, administered to the individual in need thereof at a dose of between about 250 gm to about 1 g twice daily (bid) or three times daily (tid), and optionally the amoxicillin is formulated as amoxicillin/clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a rifabutin, optionally MYCOBUTIN™, administered to the individual in need thereof at a dose of between about 50 mg to about 250 mg twice daily (bid) or three times daily (tid),
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is administered to the individual in need thereof at a dose of between 5 mg to about 200 mg or more twice daily (bid) or three times daily (tid);
- (iv)
- (1) an amoxicillin, administered to the individual in need thereof at a dose of between about 250 gm to about 1 g twice daily (bid) or three times daily (tid), and optionally the amoxicillin is formulated as amoxicillin/clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a levofloxacin, administered to the individual in need thereof at a dose of between about 100 mg to about 500 mg twice daily (bid) or three times daily (tid),
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is administered to the individual in need thereof at a dose of between 5 mg to about 200 mg or more twice daily (bid) or three times daily (tid);
- (v)
- (1) an amoxicillin, administered to the individual in need thereof at a dose of between about 250 gm to about 1 g twice daily (bid) or three times daily (tid), and optionally the amoxicillin is formulated as amoxicillin/clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a ciprofloxacin, optionally CILOXAN™, CIPRO™, NEOFLOXIN™ administered to the individual in need thereof at a dose of between about 100 mg to about 500 mg twice daily (bid) or three times daily (tid),
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is administered to the individual in need thereof at a dose of between 5 mg to about 200 mg or more twice daily (bid) or three times daily (tid);
- (vi)
- (1) an amoxicillin, administered to the individual in need thereof at a dose of between about 250 gm to about 1 g twice daily (bid) or three times daily (tid), and optionally the amoxicillin is formulated as amoxicillin/clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a moxifloxacin, optionally AVELOX™, VIGAMOX™, MOXEZA™ administered to the individual in need thereof at a dose of between about 25 mg to about 500 mg per day,
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is administered to the individual in need thereof at a dose of between 5 mg to about 200 mg or more twice daily (bid) or three times daily (tid);
- (vii)
- (1) an amoxicillin, a clarithromycin, a metronidazole, a levofloxacin, a ciprofloxacin or a moxifloxacin, administered to the individual in need thereof at a dose as set forth in any of steps (i) to (vi), optionally the amoxicillin is formulated as amoxicillin/ clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a TG44, or a 1-1000 mg/d] {[4-methylbenzyl 4′-[trans-4-(guanidine-methyl) cyclohexyl carbonyloxy]biphenyl-4-carboxylate monohydrochloride}, or CAS registry number 178748-55-5, administered to the individual in need thereof at a dose of between about 15 mg to about 50 mg per day, or at about 50 to 500 mg per day,
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is administered to the individual in need thereof at a dose of between 5 mg to about 50 mg, or 20 mg or more, twice daily (bid) or three times daily (tid);
- (viii)
- (1) an amoxicillin,
- (2) a furazolidone, optionally FUROXONE™, DEPENDAL-M™, administered to the individual in need thereof at a dose of between about 50 to about 600 mg/d, and
- (3) a rifabutin, optionally MYCOBUTIN™, administered to the individual in need thereof at a dose of between about 60 to about 450 mg/d, and optionally the rifabutin dose is ramped up starting at about 40 to about 60 g bid or tid, and optionally rising over 3 days to about 200 to about 450/d,
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is administered to the individual in need thereof at a dose as set forth in any of (i) to (vii);
- (ix) a therapeutic combination as set forth in Table 1;
- or
- (x) any combination of (i) to (ix);
- or
- (B)
- (a) vonoprazan, and
- (b) a prolonged release formulation comprising an antibiotic comprising:
- (1) amoxicillin wherein optionally the amoxicillin is formulated as amoxicillin/clavulanic acid, and/or
- (2) an antibiotic selected from the group consisting of clarithromycin, azithromycin, roxithromycin and erythromycin,
- wherein the vonoprazan is administered in an amount of 10 mg to 1 g per day, and the amoxicillin is administered in an amount of 10 mg to 6 g per day;
- or,
- (C)
- (a) a prolonged release microencapsulated and/or multimatrix formulation comprising vonoprazan, and
- (b) a prolonged release microencapsulated and/or multimatrix formulation comprising amoxicillin wherein optionally the amoxicillin is formulated as amoxicillin/clavulanic acid, or
- (c) a prolonged release microencapsulated and/or multimatrix formulation comprising vonoprazan and amoxicillin wherein optionally the amoxicillin is formulated as amoxicillin/clavulanic acid,
- wherein the vonoprazan is administered in an amount of 10 mg to 1 g per day, and the amoxicillin is administered in an amount of 1 g to 6 g per day;
- or
- (D)
- (a) vonoprazan,
- (b) a proton pump inhibitor, and
- (c) at least one antibiotic selected from the group consisting of amoxicillin, wherein optionally the amoxicillin is formulated as amoxicillin/clavulanic acid, ampicillin, pivampicillin, hetacillin, bacampicillin, metampicillin, talampicillin, epicillin, a macrolide antibiotic, furazolidone, ciprofloxacin, levofloxacin, tetracycline, a nitroimidazole antibiotic, bismuth, an ansamycin antibiotic, and nitazoxanide,
- wherein optionally the proton pump inhibitor is selected from the group consisting of omeprazole;
- pantoprazole;
- esomeprazole, lansoprazole, and rabeprazole,
- wherein optionally the macrolide antibiotic is selected from the group consisting of azithromycin, clarithromycin, erythromycin, fidaxomicin, and telithromycin,
- wherein optionally the nitroimidazole antibiotic is selected from the group consisting of metronidazole, tinidazole, and secnidazole,
- wherein optionally the ansamycin antibiotic is selected from the group consisting of rifabutin, rifampicin, rifapentin, and rifamixin;
- or
- (E)
- (i) amoxicillin, vonoprazan, furazolidone, and rifabutin;
- (ii) amoxicillin, vonoprazan, bismuth, furazolidone, rifabutin;
- (iii) amoxicillin, vonoprazan, bismuth, levofloxacin, rifabutin;
- (iv) amoxicillin, vonoprazan, levofloxacin, rifabutin;
- (v) amoxicillin, vonoprazan, bismuth, levofloxacin, furazolidone, rifabutin;
- (v) amoxicillin, vonoprazan, bismuth, tetracycline, rifabutin;
- (vi) metronidazole, vonoprazan, bismuth, tetracycline, rifabutin;
- (v) vonoprazan, bismuth, levofloxacin, rifabutin;
- or
- (vi) amoxicillin, vonoprazan, furazolidone, rifabutin, bismuth, and nitazoxanide,
- wherein optionally the amoxicillin is formulated as amoxicillin/clavulanic acid.
83 more elements
A therapeutic combination comprising:
- (a) a composition comprising or consisting of:
- vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™;
- and
- (b) an antimicrobial or antibiotic drug or composition comprising or consisting of:
- (i)
- (1) an amoxicillin, formulated for administration to the individual in need thereof at a dose of between about 1 gram (g) to about 2 g twice daily (bid), and optionally the amoxicillin is formulated as amoxicillin/ clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a clarithromycin, optionally BIAXIN™, formulated for administration to the individual in need thereof at a dose of between about 100 mg to about 2 g twice daily,
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is formulated for administration to the individual in need thereof at a dose of between 20 mg to about 50 mg twice daily (bid), or for about 25 mg or more twice daily (bid);
- (ii)
- (1) an amoxicillin, formulated for administration to the individual in need thereof at a dose of between about 500 gm to about 1 g three times daily (tid), and optionally the amoxicillin is formulated as amoxicillin/clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a metronidazole, optionally FLAGYL™, METRO™, formulated for administration to the individual in need thereof at a dose of between about 200 mg to about 500 mg three times daily (tid),
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is formulated for administration to the individual in need thereof at a dose of between 20 mg to about 50 mg three times daily (tid), or for about 25 mg or more three times daily (tid);
- (iii)
- (1) an amoxicillin, formulated for administration to the individual in need thereof at a dose of between about 250 gm to about 1 g twice daily (bid) or three times daily (tid), and optionally the amoxicillin is formulated as amoxicillin/clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a rifabutin, optionally MYCOBUTIN™, formulated for administration to the individual in need thereof at a dose of between about 50 mg to about 250 mg twice daily (bid) or three times daily (tid),
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is formulated for administration to the individual in need thereof at a dose of between 5 mg to about 200 mg or more twice daily (bid) or three times daily (tid);
- (iv)
- (1) an amoxicillin, formulated for administration to the individual in need thereof at a dose of between about 250 gm to about 1 g twice daily (bid) or three times daily (tid), and optionally the amoxicillin is formulated as amoxicillin/clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a levofloxacin, formulated for administration to the individual in need thereof at a dose of between about 100 mg to about 500 mg twice daily (bid) or three times daily (tid),
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is formulated for administration to the individual in need thereof at a dose of between 5 mg to about 200 mg or more twice daily (bid) or three times daily (tid);
- (v)
- (1) an amoxicillin, formulated for administration to the individual in need thereof at a dose of between about 250 gm to about 1 g twice daily (bid) or three times daily (tid), and optionally the amoxicillin is formulated as amoxicillin/ clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a ciprofloxacin, optionally CILOXAN™, CIPRO™, NEOFLOXIN™ formulated for administration to the individual in need thereof at a dose of between about 100 mg to about 500 mg twice daily (bid) or three times daily (tid),
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is formulated for administration to the individual in need thereof at a dose of between 5 mg to about 200 mg or more twice daily (bid) or three times daily (tid);
- (vi)
- (1) an amoxicillin, formulated for administration to the individual in need thereof at a dose of between about 250 gm to about 1 g twice daily (bid) or three times daily (tid), and optionally the amoxicillin is formulated as amoxicillin/clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a moxifloxacin, optionally AVELOX™, VIGAMOX™, MOXEZA™ formulated for administration to the individual in need thereof at a dose of between about 25 mg to about 500 mg per day,
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is formulated for administration to the individual in need thereof at a dose of between 5 mg to about 200 mg or more twice daily (bid) or three times daily (tid);
- (vii)
- (1) an amoxicillin, a clarithromycin, a metronidazole, a levofloxacin, a ciprofloxacin or a moxifloxacin, formulated for administration to the individual in need thereof at a dose as set forth in any of steps (i) to (vi), and optionally the amoxicillin is formulated as amoxicillin/ clavulanic acid, also known as co-amoxiclav, or is optionally ACTIMOXI™, ALPHAMOX™, AMOCLA™, TYCIL™, AMOXIL™, TRIMOX™;
- and
- (2) a TG44, or a 1-1000 mg/d] {[4-methylbenzyl 4′-[trans-4-(guanidine-methyl) cyclohexyl carbonyloxy]biphenyl-4-carboxylate monohydrochloride}, or CAS registry number 178748-55-5, formulated for administration to the individual in need thereof at a dose of between about 15 mg to about 50 mg per day, or at about 50 to 500 mg per day,
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is formulated for administration to the individual in need thereof at a dose of between 5 mg to about 50 mg, or 20 mg or more, twice daily (bid) or three times daily (tid);
- (viii)
- (1) an amoxicillin,
- (2) a furazolidone, optionally FUROXONE™, DEPENDAL-M™, formulated for administration to the individual in need thereof at a dose of between about 50 to about 600 mg/d, and
- (3) a rifabutin, optionally MYCOBUTIN™, formulated for administration to the individual in need thereof at a dose of between about 60 to about 450 mg/d, and optionally the rifabutin dose is ramped up starting at about 40 to about 60 g bid or tid, and optionally rising over 3 days to about 200 to about 450/d,
- wherein the vonoprazan or a vonoprazan fumarate, or a 5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine monofumarate, or a 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methyl-methanamine fumarate), optionally TAKECAB™, is formulated for administration to the individual in need thereof at a dose as set forth in any of (i) to (vii);
- (ix) a therapeutic combination as set forth in Table 1;
- or
- (x) any combination of (i) to (ix).
44 more elements
Dependencies are inferred from the claim text.