Claims for Patent: 9,498,445

Summary for Patent: 9,498,445

Title:	Pharmaceutical compositions for the treatment of Helicobacter pylori
Abstract:	Single oral solid dosage form comprising an immediate release first dosage composition having at least two antibiotic agents and a delayed release second dosage composition having a proton pump inhibitor are provided herein. The single oral solid dosage form according to some aspects of the invention can be used for the treatment of disorders associated with infection by H. pylori or the prevention of recurrence of disorders associated with infection by H. pylori.
Inventor(s):	Fathi; Reza (Oradell, NJ), Raday; Gilead (Palo Alto, CA), Goldberg; Guy (Tel Aviv, IL), Gosselin; Patrick (Laval, CA)
Assignee:	RedHill Biopharma Ltd. (Tel-Aviv, IL)
Application Number:	14/522,921
Patent Claims:	1. A capsule, comprising: (1) an immediate release first dosage composition in the form of compressed minitablets, the immediate release first dosage composition comprising a first antibiotic and at least a second antibiotic, wherein the first antibiotic is rifabutin or derivatives thereof or pharmaceutically acceptable salts or solvates thereof, wherein the first dosage composition provides, when administered at a dose of 50 mg rifabutin three times a day to a human in a fasted state, an in vivo plasma profile having: (a) a mean C.sub.max ranging from about 60 ng/ml to about 113 ng/ml; (b) a Geometric LSMeans ranging from about 55 ng/ml to about 110 ng/ml; (c) a mean AUC.sub.0-24 ranging from about 800 ngh/ml to about 1850 ngh/ml; and (d) a mean T.sub.max ranging from about 14 h to about 19 h based on a three times a day dose administration; and (2) a delayed release second dosage composition in the form of compressed minitablets, the delayed release second dosage composition comprising a proton pump inhibitor and a coating. 2. The capsule of claim 1, wherein the coating in the second dosage composition delays the release of the proton pump inhibitor from 120 to at least 240 minutes following oral administration. 3. The capsule of claim 1, wherein the at least second antibiotic in the first dosage composition is amoxicillin, derivatives thereof, or pharmaceutically acceptable salts or solvates thereof. 4. The capsule of claim 1, wherein, in the second dosage composition, the proton pump inhibitor is one of omeprazole, pantoprazole, lansoprazole, ilaprazole, dexlansoprazole, esomeprazole or rabeprazole, pharmaceutically acceptable salt or solvates thereof or combinations thereof. 5. The capsule of claim 1, wherein the second dosage composition comprises a time delay agent. 6. The capsule of claim 5, wherein the time delay agent is one of sodium alginate, glyceryl monostearate, glyceryl distearate, acrylic acids, celluloses or combinations thereof. 7. The capsule of claim 1, wherein at least 70% by weight of the first antibiotic and the at least second antibiotic is released between 5 and 120 minutes following oral administration; and at least 70% by weight of the proton inhibitor is released between 120 and 240 minutes following oral administration. 8. The capsule of claim 1 comprising rifabutin, amoxicillin and omeprazole. 9. The capsule of claim 8, wherein the amoxicillin to rifabutin ratio ranges from 10 to 40 by weight. 10. The capsule of claim 8, wherein the amoxicillin to omeprazole ratio ranges from 20 to 40 by weight. 11. The capsule of claim 1, wherein the first dosage composition comprises 250 mg amoxicillin and 12.5 mg rifabutin, derivatives thereof, or pharmaceutically acceptable salts or solvates thereof and wherein the second dosage composition comprises 10 mg omeprazole, derivatives thereof, or pharmaceutically acceptable salts or solvates thereof. 12. The capsule of claim 1, wherein the second dosage composition comprises an outer protective layer, an enteric coating and an inner protective layer. 13. The capsule of claim 1, wherein the first and second dosage compositions further comprise a filler, a disintegrant, a binder, a surfactant, an alkalizing agent, a lubricant or combinations thereof. 14. A capsule, comprising: (1) an immediate release first dosage composition in the form of compressed minitablets, the immediate release first dosage composition comprising a first antibiotic and at least a second antibiotic, wherein the first antibiotic is rifabutin or derivatives thereof or pharmaceutically acceptable salts or solvates thereof, wherein the first dosage composition provides, when administered at a dose of 50 mg three times a day to a human in a fasted state, an in vivo plasma profile having (a) a mean C.sub.max of about 87 ng/ml; (b) a Geometric LSMeans of about 85 ng/ml; (c) a mean AUC.sub.0-24 of about 1320 ngh/ml; and (d) a mean T.sub.max of about 16.50 h based on a three times a day dose administration; and (2) a delayed release second dosage composition in the form of compressed minitablets, the delayed release second dosage composition comprising a proton pump inhibitor and a coating. 15. A capsule, comprising: (1) an immediate release first dosage composition in the form of compressed minitablets, the immediate release first dosage composition comprising a first antibiotic and at least a second antibiotic, wherein the first antibiotic is rifabutin or derivatives thereof or pharmaceutically acceptable salts or solvates thereof, wherein the first dosage composition provides, when administered at a dose of 50 mg three times a day to a human in a fasted state, an in vivo plasma profile having (a) a C.sub.max to C.sub.min ratio of less than about 57.8; and (b) a mean T.sub.max of about 16.50 h based on a three times a day dose administration; and (2) a delayed release second dosage composition in the form of compressed minitablets, the delayed release second dosage composition comprising a proton pump inhibitor and a coating. 16. A method of treatment, the method comprising: administering orally a pharmaceutical composition in a single solid dosage form, wherein the pharmaceutical composition comprises (1) an immediate release first dosage composition in the form of compressed minitablets, the immediate release first dosage composition comprising a first antibiotic and at least a second antibiotic wherein the first antibiotic is rifabutin or derivatives thereof or pharmaceutically acceptable salts or solvates thereof; (2) a delayed release second dosage composition in the form of compressed minitablets, the delayed release second dosage composition comprising a proton pump inhibitor and a coating; and (3) an outer layer encapsulating the first dosage composition and the second dosage composition, wherein, in the step of administering, a dose comprising 50 mg rifabutin, 1000 mg amoxicillin and 40 mg omeprazole is administered three times a day, wherein, when the composition is administered three times a day to a human in a fasted state, an in vivo plasma profile has: (a) a mean C.sub.max ranging from about 60 ng/ml to about 113 ng/ml; (b) a Geometric LSMeans ranging from about 55 ng/ml to about 110 ng/ml; (c) a mean AUC.sub.0-24 ranging from about 800 ngh/ml to about 1850 ngh/ml; and (d) a mean T.sub.max ranging from about 14 h to about 19 h based on a three times a day dose administration. 17. The method of claim 16, wherein at least 70% by weight of the first antibiotic and the at least second antibiotic is released between 5 and 120 minutes following oral administration; and at least 70% by weight of the proton inhibitor is released between 120 and 240 minutes following oral administration. 18. A method for treating H. pylori in a host comprising administering to the host the capsule of claim 1 three times a day for at least 14 days resulting in an eradication rate greater than 84%.