WO1996019220A1 - A combination product comprising nitazoxanide and an anti-ulcer agent - Google Patents
A combination product comprising nitazoxanide and an anti-ulcer agent Download PDFInfo
- Publication number
- WO1996019220A1 WO1996019220A1 PCT/IE1995/000064 IE9500064W WO9619220A1 WO 1996019220 A1 WO1996019220 A1 WO 1996019220A1 IE 9500064 W IE9500064 W IE 9500064W WO 9619220 A1 WO9619220 A1 WO 9619220A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- combination product
- bismuth
- ulcer agent
- nitazoxanide
- ranitidine
- Prior art date
Links
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
- A61K31/33—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
- A61K31/426—1,3-Thiazoles
Definitions
- Nitazoxanide is the accepted name for 2-(acetolyloxy)-N-(S-Nitro-2- thiazolye benzamide). It is used to treat a broad range of parasitic infections.
- the combined product has the potent activity of an anti- ulcer agent and the anti-parasitic activity associated with nitazoxanide.
- the anti-ulcer agent is a histamine H 2 receptor antagonist.
- the anti- ulcer agent may be selected from cimetidine, ranitidine, famotidine, nizatidine and pharmaceutically acceptable salts thereof. Particularly preferred are ranitidine hydrochloride as Form I or Form II which are potent histamine H 2 - antagonists, and may be introduced for therapeutical use to reduce hyperacidity in the stomach.
- the anti-ulcer agent is a gastric proton pump inhibitor such as omeprazole and pharmaceutically acceptable salts thereof.
- a gastric proton pump inhibitor such as omeprazole and pharmaceutically acceptable salts thereof.
- Helicobacter pylori is associated with histologically related gastritis and hyperchlorhydria. Helicobacter pylori is particularly sensitive to the combination product of the invention.
- the weight ratio of nitazoxanide to anti-ulcer agent, particularly ranitidine hydrochloride is from 2:1 to 5:1, preferably from 3:1 to 4:1, most preferably approximately 10:3.
- the combination product includes bismuth salts which have been used extensively as antacids for the treatment of hyperacidity and dyspepsia.
- the bismuth compound is selected from bismuth citrate, bismuth subcitrate, bismuth salicylate, bismuth subsalicylate, bismuth nitrate, bismuth galate, dibismuth trietraoxidialuminate and hydrate thereof.
- the bismuth compound is bismuth subsalicylate.
- the bismuth compound is bismuth citrate.
- the combination product has improved antibacterial activity against Helicobacter pylori .
- Nitazoxanide may be administered at the same time as the anti-ulcer agent or separately.
- the combination product may be provided in a single formulation, especially for oral administration as a capsule or tablet.
- the pharmaceutical composition may contain suitable excipients and/or vehicles which are conventionally used in galenical pharmacy.
- the combination product may be used in treating gastrointestinal disorders or prophylactically.
- a batch of tablets was prepared by direct compression from the following ingredients:
- the new combinations can be formulated in any suitable galenical forms particularly for oral administration, especially as tablets or capsules.
- the preferable dosage of the present invention is 650mg to 2g, preferably 1.3g per day.
- the combination products described above have the potent anti-ulcer activity of anti-ulcer agents such as ranitidine hydrochloride combined with the antibiotic activity associated with nitazoxanide.
- the product may include bismuth salts such as bismuth subsalicylate, bismuth nitrate, bismuth subcitrate, bismuth galate, bismuth salicylate, dibismuth trietraoxidialuminate and hydrate thereof and especially bismuth citrate.
- bismuth salts such as bismuth subsalicylate, bismuth nitrate, bismuth subcitrate, bismuth galate, bismuth salicylate, dibismuth trietraoxidialuminate and hydrate thereof and especially bismuth citrate.
- the bismuth salts provide a synergistic antibacterial activity.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A combination of nitazoxanide with an anti-ulcer agent, especially ranitidine has a synergistic therapeutic profile in prophylaxis or treatment of H. pylori related infections. The product may also contain, as an antibacterial agent, bismuth salts such as bismuth subsalicylate or bismuth citrate.
Description
A COMBINATION PRODUCT COMPRISING NITAZOXANIDE AND AN ANTI-ULCER AGENT
INTRODUCTION
The invention relates to a novel combination product of nitazoxanide as well as to pharmaceutical compositions containing them and their therapeutic use. Nitazoxanide is the accepted name for 2-(acetolyloxy)-N-(S-Nitro-2- thiazolye benzamide). It is used to treat a broad range of parasitic infections.
STATEMENTS OF INVENTION
It has now been surprisingly found that a combination product of nitazoxanide and an anti-ulcer agent shows a synergistic therapeutical profile.
The combined product has the potent activity of an anti- ulcer agent and the anti-parasitic activity associated with nitazoxanide. In one embodiment of the invention the anti-ulcer agent is a histamine H2 receptor antagonist. In this case the anti- ulcer agent may be selected from cimetidine, ranitidine, famotidine, nizatidine and pharmaceutically acceptable salts thereof. Particularly preferred are ranitidine hydrochloride as Form I or Form II which are potent histamine H2- antagonists, and may be introduced for therapeutical use to reduce hyperacidity in the stomach.
In another embodiment of the invention the anti-ulcer agent is a gastric proton pump inhibitor such as omeprazole and pharmaceutically acceptable salts thereof.
In recent years it has been realised that Helicobacter pylori is associated with histologically related gastritis and hyperchlorhydria. Helicobacter pylori is particularly sensitive to the combination product of the invention. In one embodiment of the invention the weight ratio of nitazoxanide to anti-ulcer agent, particularly ranitidine hydrochloride is from 2:1 to 5:1, preferably from 3:1 to 4:1, most preferably approximately 10:3.
In one embodiment of the invention the combination product includes bismuth salts which have been used extensively as antacids for the treatment of hyperacidity and dyspepsia.
Such bismuth salts are described in British Pharmaceutical
Codex (1949) and include bismuth citrate, bismuth - and ammonium citrate, sodium bismuthyl tartarate, acidic bismuth sodium tartarate, an acidic solution of bismuth a concentrated solution of bismuth; and solutions of bismuth
- and ammonium citrate.
In one embodiment of the invention the bismuth compound is selected from bismuth citrate, bismuth subcitrate, bismuth salicylate, bismuth subsalicylate, bismuth nitrate, bismuth galate, dibismuth trietraoxidialuminate and hydrate thereof.
In a particularly preferred embodiment of the invention the bismuth compound is bismuth subsalicylate. According to another preferred embodiment of the invention the bismuth compound is bismuth citrate.
The combination product has improved antibacterial activity against Helicobacter pylori . Nitazoxanide may be administered at the same time as the anti-ulcer agent or separately. In the case of a concurrent administration
the combination product may be provided in a single formulation, especially for oral administration as a capsule or tablet. The pharmaceutical composition may contain suitable excipients and/or vehicles which are conventionally used in galenical pharmacy.
The combination product may be used in treating gastrointestinal disorders or prophylactically.
DETAILED DESCRIPTION
EXAMPLE 1
A batch of tablets was prepared by direct compression from the following ingredients:
The preferable dosage of the present invention is 650mg to 2g, preferably 1.3g per day. Preferably two separate doses, each of 650mg are administered in a twenty four hour period.
The combination products described above have the potent anti-ulcer activity of anti-ulcer agents such as ranitidine hydrochloride combined with the antibiotic activity associated with nitazoxanide.
The product may include bismuth salts such as bismuth subsalicylate, bismuth nitrate, bismuth subcitrate, bismuth galate, bismuth salicylate, dibismuth trietraoxidialuminate and hydrate thereof and especially bismuth citrate.
Where present, the bismuth salts provide a synergistic antibacterial activity.
Many variations on the specific embodiments of the invention described will be readily apparent and accordingly the invention is not limited to the embodiments described which may be varied in detail.
Claims
1. A combination product comprising nitazoxanide and an anti-ulcer agent.
2. A combination product as claimed in claim 1 wherein the anti-ulcer agent is a histamine H2 receptor antagonist.
3. A combination product as claimed in claim 1 or 2 wherein the anti-ulcer agent is selected from cimetidine, ranitidine, famotidine, nizatidine and pharmaceutically acceptable salts thereof .
4. A combination product as claimed in any of claims
1 to 3 wherein the anti-ulcer agent is ranitidine.
5. A combination product as claimed in any preceding claim wherein the anti-ulcer agent is ranitidine hydrochloride - Form II.
6. A combination product as claimed in any of claims
1 to 4 wherein the anti-ulcer agent is ranitidine hydrochloride - Form I .
7. A combination product as claimed in any preceding claim wherein the weight ratio of nitazoxanide to anti-ulcer agent is from 2:1 to 5:1.
8. A combination product as claimed in claim 7 wherein the weight ratio is from 3:1 to 4:1.
9. A combination product as claimed in claim 7 or 8 wherein the weight ratio is approximately 10:3.
10. A combination product as claimed in claim 1 or any of claims 7 to 9 wherein the anti-ulcer agent is a gastric proton pump inhibitor.
11. A combination product as claimed in claim 1 or any of claims 7 to 10 wherein the anti-ulcer agent is omeprazole and pharmaceutically acceptable salts thereof.
12. A combination product as claimed in any preceding claim including a bismuth compound.
13. A combination product as claimed in claim 12 wherein the bismuth compound is selected from bismuth citrate, bismuth subcitrate, bismuth salicylate, bismuth subsalicylate, bismuth nitrate, bismuth galate, dibismuth trietraoxidialuminate and hydrate thereof.
14. A combination product as claimed in claim 12 or 13 wherein the bismuth compound is bismuth subsalicylate.
15. A combination product as claimed in claim 12 or 13 wherein the bismuth compound is bismuth citrate.
16. A combination product substantially as hereinbefore described with reference to the example.
17. A pharmaceutical composition for oral administration incorporating a combination product as claimed in any preceding claim.
18. A composition as claimed in claim 17 in the form of a tablet.
19. A composition as claimed in claim 17 in the form of a capsule.
20. A pharmaceutical composition for oral administration comprising nitazoxanide and ranitidine hydrochloride.
21. A pharmaceutical composition for oral administration comprising nitazoxanide and ranitidine hydrochloride in a weight ratio of approximately 10:3.
22. A pharmaceutical composition substantially as hereinbefore described with reference to the example.
23. Use of a combination product as claimed in any of claims 1 to 16 for the prophylaxis or treatment of H. pylori related infections.
24. Use of a combination product substantially as hereinbefore described with reference to the example.
25. A method of prophylaxis or treatment of H. pylori related infections comprising administering combination product as claimed in any of claims 1 to 16.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU43992/96A AU4399296A (en) | 1994-12-19 | 1995-12-19 | A combination product comprising nitazoxanide and an anti-ulcer agent |
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE940972 | 1994-12-19 | ||
| IE940972 | 1994-12-19 | ||
| IE950090 | 1995-02-06 | ||
| IE950090A IE950090A1 (en) | 1995-02-06 | 1995-02-06 | Pharmaceutical composition |
| IE950149 | 1995-02-23 | ||
| IE950149 | 1995-02-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1996019220A1 true WO1996019220A1 (en) | 1996-06-27 |
Family
ID=27270487
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IE1995/000064 WO1996019220A1 (en) | 1994-12-19 | 1995-12-19 | A combination product comprising nitazoxanide and an anti-ulcer agent |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU4399296A (en) |
| WO (1) | WO1996019220A1 (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8895077B2 (en) * | 2007-04-02 | 2014-11-25 | Mount Sinai School Of Medicine | Methods for preventing or treating infectious diseases caused by extracellular microorganisms, including antimicrobial-resistant strains thereof, using gallium compounds |
| WO2018167103A1 (en) * | 2017-03-13 | 2018-09-20 | Genfit | Pharmaceutical compositions for combination therapy |
| WO2020176067A1 (en) * | 2019-02-25 | 2020-09-03 | Rhode Island Hospital | Methods for treating diseases or infections caused by or associated with h. pylori using a halogenated salicylanilide |
| US11285164B2 (en) | 2014-09-12 | 2022-03-29 | UNION therapeutics A/S | Antibacterial use of halogenated salicylanilides |
| US11419834B2 (en) | 2019-02-25 | 2022-08-23 | Rhode Island Hospital | Methods for treating diseases or infections caused by or associated with H. pylori using a halogenated salicylanilide |
| US11529361B2 (en) | 2015-05-29 | 2022-12-20 | UNION therapeutics A/S | Halogenated salicylanilides for treating Clostridium infections |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0480691A2 (en) * | 1990-10-11 | 1992-04-15 | Merck & Co. Inc. | Combination therapy for peptic ulcer treatment |
| DE4317449A1 (en) * | 1993-05-19 | 1994-11-24 | Asche Ag | Pharmaceutical composition for the treatment of disorders of the gastrointestinal tract |
-
1995
- 1995-12-19 AU AU43992/96A patent/AU4399296A/en not_active Abandoned
- 1995-12-19 WO PCT/IE1995/000064 patent/WO1996019220A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0480691A2 (en) * | 1990-10-11 | 1992-04-15 | Merck & Co. Inc. | Combination therapy for peptic ulcer treatment |
| DE4317449A1 (en) * | 1993-05-19 | 1994-11-24 | Asche Ag | Pharmaceutical composition for the treatment of disorders of the gastrointestinal tract |
Non-Patent Citations (2)
| Title |
|---|
| J.R. MURPHY ET AL.: "Pre-clinical toxicology of nitazoxanide, a new antiparasitic compound.", J.APPL. TOXICOL., vol. 5, no. 2, 1985, pages 49 - 52, XP000569036 * |
| R. CAVIER ET AL.: "Pharmacologic study of various anthelmintic combinations.", REV. MED. VET., vol. 133, no. 12, 1982, pages 779 - 783, XP000569161 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8895077B2 (en) * | 2007-04-02 | 2014-11-25 | Mount Sinai School Of Medicine | Methods for preventing or treating infectious diseases caused by extracellular microorganisms, including antimicrobial-resistant strains thereof, using gallium compounds |
| US11285164B2 (en) | 2014-09-12 | 2022-03-29 | UNION therapeutics A/S | Antibacterial use of halogenated salicylanilides |
| US11324761B2 (en) | 2014-09-12 | 2022-05-10 | UNION therapeutics A/S | Antibacterial use of halogenated salicylanilides |
| US11331327B2 (en) | 2014-09-12 | 2022-05-17 | UNION therapeutics A/S | Antibacterial use of halogenated salicylanilides |
| US11529361B2 (en) | 2015-05-29 | 2022-12-20 | UNION therapeutics A/S | Halogenated salicylanilides for treating Clostridium infections |
| WO2018167103A1 (en) * | 2017-03-13 | 2018-09-20 | Genfit | Pharmaceutical compositions for combination therapy |
| CN110430876A (en) * | 2017-03-13 | 2019-11-08 | 基恩菲特公司 | Pharmaceutical composition for combination treatment |
| US11191749B2 (en) | 2017-03-13 | 2021-12-07 | Genfit | Pharmaceutical compositions for combination therapy |
| IL268751B (en) * | 2017-03-13 | 2022-08-01 | Genfit | Pharmaceutical compositions for combination therapy |
| WO2020176067A1 (en) * | 2019-02-25 | 2020-09-03 | Rhode Island Hospital | Methods for treating diseases or infections caused by or associated with h. pylori using a halogenated salicylanilide |
| US11419834B2 (en) | 2019-02-25 | 2022-08-23 | Rhode Island Hospital | Methods for treating diseases or infections caused by or associated with H. pylori using a halogenated salicylanilide |
Also Published As
| Publication number | Publication date |
|---|---|
| AU4399296A (en) | 1996-07-10 |
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