WO2006043280A1 - Tenatoprazole salts and process of preparation thereof - Google Patents

Tenatoprazole salts and process of preparation thereof Download PDF

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WO2006043280A1
WO2006043280A1 PCT/IN2004/000328 IN2004000328W WO2006043280A1 WO 2006043280 A1 WO2006043280 A1 WO 2006043280A1 IN 2004000328 W IN2004000328 W IN 2004000328W WO 2006043280 A1 WO2006043280 A1 WO 2006043280A1
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formula
tenatoprazole
methoxy
salt
salts
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PCT/IN2004/000328
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French (fr)
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Ramesh Anna Joshi
Rohini Ramesh Joshi
Vijay Naryan Wakchaure
Mukund Keshav Gurjar
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Council Of Scientific And Industrial Research
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04Ortho-condensed systems

Definitions

  • the present invention relates to of salts of 5-methoxy-2-(4-methoxy-3,5- dimethylpyridin-2-ylmethylsulfinyl) imidazo[4,5-b]pyridine (Tenatoprazole) and to a process for the preparation thereof.
  • the Tenatoprazole salts of the invention have the formula (1)
  • FORMUU (1) wherein X is Li, Na, Ca, K or Mg. More particularly the present invention relates to a process of preparing the salts of formula (1) by oxidizing a compound of formula (2).
  • the main object of the present invention is to provide a process for the preparation of salts of Tenatoprozole having formula (1) wherein X is Li, Na, Ca, K or Mg.
  • the present invention provides salts of 5-methoxy-2-(4-methoxy-3,5- dimethylpyridin-2-ylmethylsulfinyl) imidazo[4,5-b]pyridine (Tenatoprazole) of formula (1)
  • the present invention also provides a process for the preparation of 5-methoxy-2-(4- methoxy-3,5-dimethylpyridin-2-ylmethylsulfinyl) imidazo[4,5-b]pyridine (Tenatoprazole) salts of formula (1)
  • step (d) washing the alkali extract with the solvent used in step (a); (e) separating the aqueous layer and agitating at room temperature to obtain the compound of formula (1).
  • step (b) the organic layer is washed with saturated bicarbonate solution of sodium or potassium.
  • the oxidizing agent is a peracid selected from the group consisting of m-chloroperbenzoic acid, perbenzoic acid and peracetic acid.
  • the concentration of oxidizing agent is in the range of 1 to 1.3 mole per mole of sulfide of formula (2).
  • the solvent used is a halogenated hydrocarbon selected from the group consisting of chloroform and terachloroethane; or an alcohol selected from the group consisting of methanol, ethanol, propanol and butanol; or a mixture of any two or more thereof.
  • the aqueous alkali is selected from the group consisting of hydroxides of Na, K and Li.
  • the Ca and Mg salts of compound of formula (1) are prepared by treating Na, K or Li salt of tenatoprazole with halides of Mg and Ca or Mg(OR) 2 Ca(OR) 2 wherein R is an alkyl group containing 1-4 carbon unit.
  • the present invention provides salts of 5-methoxy-2-(4-methoxy-3,5- dimethylpyridin-2-ylmethylsulfinyl) imidazo[4,5-b]pyridine (Tenatoprazole) of formula (1)
  • the salts of formula (1) are prepared by oxidizing a sulfide compound of formula (2)
  • FORMULA (2) in the presence of an organic solvent.
  • the organic layer so formed is then separated and washed, preferably with saturated bicarbonate solution of sodium or potassium, and then extracted with an aqueous alkali.
  • the alkali extract is washed with the same solvent and the aqueous layer so obtained is separated and agitated preferably at room temperature to obtain the compound of formula (1).
  • the oxidizing agent is a peracid selected from the group consisting of m- chloroperbenzoic acid, perbenzoic acid and peracetic acid.
  • concentration of oxidizing agent is in the range of 1 to 1.3 mole per mole of sulfide of formula (2).
  • the solvent used is a halogenated hydrocarbon selected from the group consisting of chloroform and terachloroethane; or an alcohol selected from the group consisting of methanol, ethanol, propanol and butanol; or a mixture of any two or more thereof.
  • the aqueous alkali is selected from the group consisting of hydroxides of Na, K and Li.
  • the Ca and Mg salts of compound of formula (1) are prepared by treating Na, K or Li salt of tenatoprazole with halides of Mg and Ca or Mg(OR) 2 Ca(OR) 2 wherein R is an alkyl group containing 1-4 carbon unit.
  • Tenatoprozole salts of Formula (I) are being extensively investigated clinically as a gastric acid secretion inhibiting agent.
  • the present invention provides such new salts/forms of tenatoprazole which exhibit improved storage stability.
  • the salts of the formula (1) are also easier to handle than the neutral form in the manufacture of pharmaceutical dosage unit.
  • Preferred salts are those wherein X is Na + , Mg 2+ .
  • the Na + salt is especially preferred for the preparation of liquid pharmaceutical formulations e.g. solutions for intravenous administration.
  • the Mg 2+ salts are especially preferred for the preparation of tablets.
  • different salts of tenatoprazole were prepared without isolating free base.
  • the salts of the invention are prepared by reacting tenatoprazole with a base capable of releasing the cation X wherein X (n+) is as defined above to give a salt of the formula which salt is thereafter isolated.
  • the process of the present invention is described hereinbelow with reference to tne examples which are illustrative only and should not be construed to limit the scope of the present invention in any manner.
  • Example 1 This example describes the preparation of 5-methoxy 2-[[(4-methoxy-3, 5-dimethyl)-2- pyridyl methyl] sulfinyl] IH imidazo [4, 5-bJ pyridine, Sodium Salt dihydrate:
  • This example describes preparation of di-tenatoprazole calcium salt dihydrate: Calcium chloride (0.18 gm, 1.62 mmol) dissolved in deionised water (10 ml) was added drop wise under vigorous stirring to a solution of tenatoprazole sodium (1 gm, 2.7 mmol,) in deionised water (30 ml) and then stirring was continued for 1 h. at room temperature.
  • the present invention provides the method for preparation of stable novel salts of formula (1) in a single step i.e. without isolating 5-methoxy-2-(4-methoxy-3,5- dimethylpyridin-2-ylmethylsulfinyl) imidazo [4,5-b] pyridine in free form from reaction mixture. 2.
  • the invention also provides the method for preparation of Ca and Mg salts of

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The present invention relates to of salts of 5-methoxy-2-(4-methoxy-3,5dimethylpyridin-2-ylmethylsulfinyl) imidazo[4,5-­b]pyridine (Tenatoprazole) of formula (1) wherein X is Li, Na, Ca, K or Mg and to a process for the preparation thereof which comprises oxidizing a compound of formula (2) and isolating the salt (Li, Na) by treatment with the alkali hydroxide or exchanging the sodium salt of tenatoprazole with Mg++ or Ca++ cation.

Description

TENATOPRAZOLE SALTS AND PROCESS OF PREPARATION THEREOF Field of the invention
The present invention relates to of salts of 5-methoxy-2-(4-methoxy-3,5- dimethylpyridin-2-ylmethylsulfinyl) imidazo[4,5-b]pyridine (Tenatoprazole) and to a process for the preparation thereof. The Tenatoprazole salts of the invention have the formula (1)
Figure imgf000002_0001
10
FORMUU (1) wherein X is Li, Na, Ca, K or Mg. More particularly the present invention relates to a process of preparing the salts of formula (1) by oxidizing a compound of formula (2).
Figure imgf000002_0002
FORMULA (2) Background of the invention
In the prior art US patent 4,738,974 teaches the preparation of salts of omeprazole, mentions compositions consisting of salts of tenatoprazole however no details of the method of preparations of the said salts of tenatoprazole, their physical constants, characterization has been reported. Claim No. 14 of the PCT patent No. (PCT/SE94/00006 WO 95/18612) mentions along with others that the active substance TU 199 (Tenatoprazole) can be administered in the form of basic salts such as magnesium or sodium. Preparation of Tenatoprazole in free form as disclosed in patent EP-0254588 involves use of very dilute solution of sulfide in chloroform (100 ml per gram of sulfied ) making it difficult for scale up. Objects of the invention The main object of the present invention is to provide a process for the preparation of salts of Tenatoprozole having formula (1) wherein X is Li, Na, Ca, K or Mg.
Another object is to isolate salts of Tenatoprozole such as Na, K, Li from oxidation reaction mixture in single step thus avoiding the separation of free sulfinyl compund. Yet another object is to prepare salts such as Ca, Mg from sodium salt of Tenatoprazole. Summary of the invention
Accordingly the present invention provides salts of 5-methoxy-2-(4-methoxy-3,5- dimethylpyridin-2-ylmethylsulfinyl) imidazo[4,5-b]pyridine (Tenatoprazole) of formula (1)
Figure imgf000003_0001
FORMULA (1) wherein X=Na, K, Li, Mg5 Ca.
The present invention also provides a process for the preparation of 5-methoxy-2-(4- methoxy-3,5-dimethylpyridin-2-ylmethylsulfinyl) imidazo[4,5-b]pyridine (Tenatoprazole) salts of formula (1)
Figure imgf000003_0002
FORMULA (1) wherein X=Na, K, Li, Mg, Ca which comprises:
(a) oxidizing a sulfide compound of formula (2)
Figure imgf000003_0003
FORMULA (2)
in the presence of an organic solvent to obtain an organic layer;
(b) separating and washing the organic layer;
(c) extracting the organic layer with an aqueous alkali;
(d) washing the alkali extract with the solvent used in step (a); (e) separating the aqueous layer and agitating at room temperature to obtain the compound of formula (1).
In one embodiment of the invention, in step (b), the organic layer is washed with saturated bicarbonate solution of sodium or potassium. In one of embodiment of the invention the oxidizing agent is a peracid selected from the group consisting of m-chloroperbenzoic acid, perbenzoic acid and peracetic acid.
In another embodiment of the invention, the concentration of oxidizing agent is in the range of 1 to 1.3 mole per mole of sulfide of formula (2).
In another embodiment of the invention, the solvent used is a halogenated hydrocarbon selected from the group consisting of chloroform and terachloroethane; or an alcohol selected from the group consisting of methanol, ethanol, propanol and butanol; or a mixture of any two or more thereof.
In another embodiment of the invention the aqueous alkali is selected from the group consisting of hydroxides of Na, K and Li. In yet another embodiment of the invention the Ca and Mg salts of compound of formula (1) are prepared by treating Na, K or Li salt of tenatoprazole with halides of Mg and Ca or Mg(OR)2 Ca(OR)2 wherein R is an alkyl group containing 1-4 carbon unit. Detailed description of the invention
The present invention provides salts of 5-methoxy-2-(4-methoxy-3,5- dimethylpyridin-2-ylmethylsulfinyl) imidazo[4,5-b]pyridine (Tenatoprazole) of formula (1)
Figure imgf000004_0001
FORMULA (1) wherein X=Na, K, Li, Mg, Ca.
The salts of formula (1) are prepared by oxidizing a sulfide compound of formula (2)
Figure imgf000004_0002
FORMULA (2) in the presence of an organic solvent. The organic layer so formed is then separated and washed, preferably with saturated bicarbonate solution of sodium or potassium, and then extracted with an aqueous alkali. The alkali extract is washed with the same solvent and the aqueous layer so obtained is separated and agitated preferably at room temperature to obtain the compound of formula (1).
The oxidizing agent is a peracid selected from the group consisting of m- chloroperbenzoic acid, perbenzoic acid and peracetic acid. The concentration of oxidizing agent is in the range of 1 to 1.3 mole per mole of sulfide of formula (2). The solvent used is a halogenated hydrocarbon selected from the group consisting of chloroform and terachloroethane; or an alcohol selected from the group consisting of methanol, ethanol, propanol and butanol; or a mixture of any two or more thereof. The aqueous alkali is selected from the group consisting of hydroxides of Na, K and Li. The Ca and Mg salts of compound of formula (1) are prepared by treating Na, K or Li salt of tenatoprazole with halides of Mg and Ca or Mg(OR)2 Ca(OR)2 wherein R is an alkyl group containing 1-4 carbon unit. Tenatoprozole salts of Formula (I) are being extensively investigated clinically as a gastric acid secretion inhibiting agent.
A problem with this type of drugs i.e. proton pump inhibitors having methyl sulfinyl group, is their stability characteristics. Upon storage without any special precautions being taken they degrade at a rate, which is higher than desired. It is desirable to obtain physical forms which exhibit improved stability. This need for more stable form is apparent, considering the often longer time periods involved from the synthesis of the active substance through its incorporation in pharmaceutical preparations, distribution of the finished product to pharmacies etc. up to the consumption of the preparation by patient. The present invention provides such new salts/forms of tenatoprazole which exhibit improved storage stability. The salts of the formula (1) are also easier to handle than the neutral form in the manufacture of pharmaceutical dosage unit.
Preferred salts are those wherein X is Na+, Mg2+. The Na+ salt is especially preferred for the preparation of liquid pharmaceutical formulations e.g. solutions for intravenous administration. The Mg2+ salts are especially preferred for the preparation of tablets. In order to overcome it's low storage stability, different salts of tenatoprazole were prepared without isolating free base.
The salts of the invention are prepared by reacting tenatoprazole with a base capable of releasing the cation X wherein X(n+) is as defined above to give a salt of the formula which salt is thereafter isolated. The process of the present invention is described hereinbelow with reference to tne examples which are illustrative only and should not be construed to limit the scope of the present invention in any manner. Example 1 This example describes the preparation of 5-methoxy 2-[[(4-methoxy-3, 5-dimethyl)-2- pyridyl methyl] sulfinyl] IH imidazo [4, 5-bJ pyridine, Sodium Salt dihydrate:
To a solution of 5-methoxy 2-[[(4-methoxy-3,5-dimethyl)-2-pyridyl methyl] thio]lH imidazo [4,5-b]pyridine (20 gm.; 60.6 mmol.) in chloroform (400ml), an aqueous solution of potassium bicarbonate (8 gm.; 79.9 mmol., in 60 ml H2O) was added and cooled to 0-50C. m- CPBA solution (20 gm; 55-75%. in 130 ml Chloroform) was added drop wise over a period of 1 hr 25 min. at 0-5° C with stirring. After complete addition reaction mixture was stirred at 0-5° C for 20 min. The completion of the oxidation was followed by TLC ( 2% methanol in chloroform). Organic layer was separated and washed with saturated solution of potassium bicarbonate. Organic layer was extracted with sodium hydroxide solution (4.8 gm, NaOH in 130 ml H20) Alkaline extract again washed with chloroform (2 X 50 ml chloroform). Alkaline extract was depressurized on rotavapour to remove traces of chloroform. Aqueous layer then stirred for 20 minutes and precipitated solid was filtered off to get 21.5 gm of crude sodium salt. This was further purified by recrystallisation [ dϋsopropyl ether (80 ml) and dimethyl formamide (53 ml)] to obtain pure sodium salt of tenatoprazole (16.8 gm, 76 % ) mp 224-226 0C
1HNMR: (DMSO-dtf) 2.15(s, 3H), 2.20 (s,3H), 3.68 (s, 3H), 3.71 (s, 3H), 4.41 and 4.58 (AB- system, J= 12.9 Hz, 2H), 6.56 (dd, J=8.5 Hz and 2.4 Hz, IH), 7.00 (d, J=2.4 Hz, IH), 7.34 (d, J=8.5 Hz), 8.30 (s, IH). Analysis-Calcd for C16H17N4O3S Na,2H2O: C, 47.5;H,4.2; N.13.86; S,7.92; Found: C, 46.61; H, 5.69; N.13.77; S/7.89. Example 2
This example describes the preparation of 5-methoxy 2-[[(4-methoxy-3, 5-dimethyl)- 2-pyridyl methyl] sulfinyl] IH imidazo [4,5-b] ' pyridine, Potassium Salt:
To a solution of 5-methoxy 2-[[(4-methoxy-3,5-dimethyl)-2-pyridyl methyl] thio]lH imidazo [4,5-b]pyridine (1 gm, 3 mmol.) in chloroform (15ml), an aqueous solution of potassium bicarbonate (0.2 gm.; 2 mmol, in 5 ml H2O) was added and cooled to 0-50C. m- CPBA solution (lgm;. 55-75%. in 15 ml Chloroform) was added drop wise over a period of 1 hr 25 min. at 0-5° C with stirring. After complete addition reaction mixture was stirred at 0-5° C for 20 min. The completion of the oxidation was followed by TLC ( 2 % methanol in chloroform ). Organic layer was separated and washed with saturated solution of potassium bicarbonate. Organic layer was extracted with potassium hydroxide solution (0.160 gm. KOH in 6 ml H2O) Alkaline extract again washed with chloroform (2 X 10 ml chloroform). Alkaline extract was depressurized on rotavapour to remove traces of chloroform. Aqueous layer then stirred for 20 minutes and filtered clear (celite). Evaporation to dryness gave a crystalline residue. Recrystallisation from Dimethyl formamide and Diisopropyl ether yielded tenatoprazole potassium salt (0.85 g, 69%), mp 159-1610C. Example 3
This example describes the preparation of 5-methoxy 2-[[(4~methoxy-3, 5-dimethyl)- 2-pyridyl methyl] sulfinyl] IH imidazo [4, 5 -b] pyridine, lithium Salt:
To a solution of 5-methoxy 2-[[(4-methoxy-3,5-diniethyl)~2-pyridyl methyl] thio]lH imidazo [4,5-b]pyridine (1 gm.; 3 mmol) in chloroform (40ml), an aqueous solution of potassium bicarbonate (0.2 gm, 2 mmol, in 5 ml H2O) was added and cooled to 0-50C. m- CPBA solution (1 gm; 55-75%. in 15 ml Chloroform) was added drop wise over a period of 1 hr 25 min. at 0-5° C with stirring. After complete addition reaction mixture was stirred at 0-5° C for 20 min. The completion of the oxidation was followed by TLC ( 2 % methanol in chloroform). Organic layer was separated and washed with saturated solution of potassium bicarbonate. Organic layer was extracted with lithium hydroxide solution (0.160 gm, LiOH in 10 ml H2O) Alkaline extract again washed with chloroform (2 X 10 ml chloroform). Alkaline extract was depressurized on rotavapour to remove traces of chloroform. Aqueous layer then stirred for 20 minutes and precipitated solid was filtered off, dried. Recrystallisation from Dimethyl formamide and Diisopropyl ether and acetonitrile yielded tenatoprazole lithium salt (0.73 g, 71%) mp l96-197°C. Example 4 This example describes preparation of di-tenatoprazole magnesium salt dihydrate :
Magnesium chloride (0.18 gm, 1.9 mmol) dissolved in deionised water (10 ml) was added drop wise under vigorous stirring to a solution of tenatoprzole sodium (1 gm, 2.7 mmol) in deionised water (30 ml) and then stirring was continued for 1 h. Precipitated solid was filtered off, dried, and then recrystallised in dimethyl fomamide and diisopropyl ether and acetonitrile yielded di-tenatoprazole magnesium salt (0.65 g, 61%) mp 190-1910C. Example 5
This example describes preparation of di-tenatoprazole calcium salt dihydrate: Calcium chloride (0.18 gm, 1.62 mmol) dissolved in deionised water (10 ml) was added drop wise under vigorous stirring to a solution of tenatoprazole sodium (1 gm, 2.7 mmol,) in deionised water (30 ml) and then stirring was continued for 1 h. at room temperature. Precipitated solid was filtered off washed with deionised water until no Cl" was detectable (AgNO3), dried, and recrystallised in dimethyl fomamide and diisopropyl ether and acetonitrile yielded di-tenatoprazole calcium salt (0.88 g, 80%) mp 194-1960C. The main advantages of the process are:
1. ' The present invention provides the method for preparation of stable novel salts of formula (1) in a single step i.e. without isolating 5-methoxy-2-(4-methoxy-3,5- dimethylpyridin-2-ylmethylsulfinyl) imidazo [4,5-b] pyridine in free form from reaction mixture. 2. The invention also provides the method for preparation of Ca and Mg salts of
Tenatoprazole from its sodium salt.

Claims

We claim:
1. 5-methoxy-2-(4-methoxy-3 , 5-dimethylpyridin-2-ylmethylsulfinyl) imidazo[4,5-b] pyridine (Tenatoprazole) salt of formula (1)
Figure imgf000009_0001
FORMULA (1) wherein X=Na, K, Li, Mg, Ca.
2. A process for the preparation of 5-methoxy-2-(4-methoxy-3,5-dimethylpyridin-2- ylmethylsulfinyl) imidazo[4,5-b]pyridine (Tenatoprazole) salt of formula (1)
Figure imgf000009_0002
FORMULA (1) wherein X=Na, K, Li, Mg, Ca which comprises:
(a) oxidizing a sulfide compound of formula (2)
Figure imgf000009_0003
FORMULA (2)
in the presence of an organic solvent to obtain an organic layer;
(b) separating and washing the organic layer;
(c) extracting the organic layer with an aqueous alkali;
(d) washing the alkali extract with the solvent used in step (a);
(e) separating the aqueous layer and agitating at room temperature to obtain the compound of formula (1).
3. A process as claimed in claim 2 wherein in step (b), the organic layer is washed with saturated bicarbonate solution of sodium or potassium.
4. A process as claimed in claim 2 wherein the oxidizing agent is a peracid selected from the group consisting of m-chloroperbenzoic acid, perbenzoic acid and peracetic acid.
5. A process as claimed in claim 2 wherein the concentration of oxidizing agent is in the range of 1 to 1.3 mole per mole of sulfide of formula (2).
6. A process as claimed in claim 2 wherein the solvent used is a halogenated hydrocarbon selected from the group consisting of chloroform and terachloro ethane; or an alcohol selected from the group consisting of methanol, ethanol, propanol and butanol; or a mixture of any two or more thereof.
7. A process as claimed in claim 2 wherein the aqueous alkali is selected from the group consisting of hydroxides of Na, K and Li.
8. A process as claimed in claim 2 wherein the compound of formula (1) is a Ca and Mg salt and is obtained by treating Na, K or Li salt of tenatoprazole with halides of Mg and Ca or Mg(OR)2 Ca(OR)2 wherein R is an alkyl group containing 1 -4 carbon unit.
PCT/IN2004/000328 2004-10-19 2004-10-19 Tenatoprazole salts and process of preparation thereof WO2006043280A1 (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100376574C (en) * 2006-06-14 2008-03-26 浙江大学 Preparation process of taytrolazole
FR2909380A1 (en) * 2006-12-04 2008-06-06 Sidem Pharma Sa Sa Potassium tenatoprazole salts containing an equimolar mixture of enantiomers of R and S configuration, crystallizing in the form of the conglomerate
WO2009105568A1 (en) 2008-02-20 2009-08-27 The Curators Of The University Of Missouri Composition comprising a combination of omeprazole and lansoprazole, and a buffering agent, and methods of using same
EP2486910A2 (en) 2006-10-27 2012-08-15 The Curators Of The University Of Missouri Multi-chambered apparatus comprising a dispenser head

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WO1995018612A1 (en) * 1994-01-05 1995-07-13 Aktiebolaget Astra A method for treatment of psoriasis, by omeprazole or related compounds
WO2004037256A1 (en) * 2002-10-21 2004-05-06 Sidem Pharma Pharmaceutical composition combining tenatoprazole and a histamine h2-receptor antagonist
WO2004037254A1 (en) * 2002-10-21 2004-05-06 Sidem Pharma Pharmaceutical composition combining tenatoprazole and an anti-inflammatory agent
WO2004060891A1 (en) * 2002-12-16 2004-07-22 Sidem Pharma Sa Enantiomer (-) of tenatoprazole and the therapeutic use thereof
WO2004074285A1 (en) * 2003-02-24 2004-09-02 Mitsubishi Pharma Corporation The enantiomer of tenatoprazole and the use thereof in therapy

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995018612A1 (en) * 1994-01-05 1995-07-13 Aktiebolaget Astra A method for treatment of psoriasis, by omeprazole or related compounds
WO2004037256A1 (en) * 2002-10-21 2004-05-06 Sidem Pharma Pharmaceutical composition combining tenatoprazole and a histamine h2-receptor antagonist
WO2004037254A1 (en) * 2002-10-21 2004-05-06 Sidem Pharma Pharmaceutical composition combining tenatoprazole and an anti-inflammatory agent
WO2004060891A1 (en) * 2002-12-16 2004-07-22 Sidem Pharma Sa Enantiomer (-) of tenatoprazole and the therapeutic use thereof
WO2004074285A1 (en) * 2003-02-24 2004-09-02 Mitsubishi Pharma Corporation The enantiomer of tenatoprazole and the use thereof in therapy

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100376574C (en) * 2006-06-14 2008-03-26 浙江大学 Preparation process of taytrolazole
EP2486910A2 (en) 2006-10-27 2012-08-15 The Curators Of The University Of Missouri Multi-chambered apparatus comprising a dispenser head
FR2909380A1 (en) * 2006-12-04 2008-06-06 Sidem Pharma Sa Sa Potassium tenatoprazole salts containing an equimolar mixture of enantiomers of R and S configuration, crystallizing in the form of the conglomerate
WO2008081104A3 (en) * 2006-12-04 2008-09-04 Sidem Pharma Sa Conglomerates of tenatoprazole potassium salts
JP2010511679A (en) * 2006-12-04 2010-04-15 シデム ファーマ ソシエテ アノニム Conglomerate of tenatoprazole potassium salt
US20110060002A1 (en) * 2006-12-04 2011-03-10 Sidem Pharama Sa Conglomerates of tenatoprazole potassium salts
US8546574B2 (en) 2006-12-04 2013-10-01 Sidem Pharma Sa Conglomerates of tenatoprazole potassium salts
WO2009105568A1 (en) 2008-02-20 2009-08-27 The Curators Of The University Of Missouri Composition comprising a combination of omeprazole and lansoprazole, and a buffering agent, and methods of using same

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