WO2004096770A1 - Process for preparing almodipine mesylate monohydrate - Google Patents
Process for preparing almodipine mesylate monohydrate Download PDFInfo
- Publication number
- WO2004096770A1 WO2004096770A1 PCT/GB2004/001638 GB2004001638W WO2004096770A1 WO 2004096770 A1 WO2004096770 A1 WO 2004096770A1 GB 2004001638 W GB2004001638 W GB 2004001638W WO 2004096770 A1 WO2004096770 A1 WO 2004096770A1
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- WIPO (PCT)
- Prior art keywords
- amlodipine
- solvent medium
- amlodipine mesylate
- process according
- monohydrate
- 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.)
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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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
Definitions
- the present invention is concerned with a process for preparing amlodipine mesylate monohydrate.
- Amlodipine is the international non-proprietary name of 2-[(2-Aminoethoxy)- methyl]-4-(2-chlorophenyl)-l,4-dihydro-6-methyl-3,5-pyridinecarboxylic acid 3-ethyl 5- methyl ester.
- Amlodipine is known to be a calcium channel blocker and has therapeutic applications in the treatment or prevention of a number of cardiac conditions, such as angina pectoris, cardiac arrythmias, heart attacks, cardiac hypertrophy and related cardiac conditions, and also as an antihypertensive agent, for example in the treatment of coronary vasospasm.
- Amlodipine is the title compound of Example 9 of European Patent 0089167B and its preparation is described therein.
- European Patent 0089167B describes suitable pharmaceutically acceptable salts of the compounds described therein, including the hydrochloride, hydrobromide, sulphate, phosphate or acid phosphate, acetate, maleate, fumarate, lactate, tartrate, citrate and gluconate salts. Maleate is described as the preferred salt.
- the preparation of the maleate salt of amlodipine is described in Examples 11 and 12 of European Patent 0089167B.
- European Patent Application 0244944A describes further salts of amlodipine, and describes the besylate salt of amlodipine as being a particularly preferred salt.
- US Patent 6057344 describes the use of (-)amlodipine, substantially free of its (+) stereoisomer, in eliciting an antihypertensive effect and also for use in the treatment of angina.
- Preferred pharmaceutically acceptable salts described in US Patent 6057344 are derived from besylate, hydrobromic, hydrochloric, phosphoric and sulphuric acids.
- US Patent Application 2002/0045648 describes a pharmaceutical composition comprising an NO-releasing amount of the R(+)enantiomer of amlodipine or of a pharmaceutically acceptable salt thereof, an antihypertensive amount of the S(-) enantiomer of amlodipine or of a pharmaceutically acceptable salt thereof and a suitable excipient, diluent or carrier, wherein the enantiomers are present in a ratio by weight (based on free base) of R(+)enantiomer: S(-)enantiomer of greater than 1:1.
- European patent application 1221438 A describes the preparation of two different crystalline forms of amlodipine mesylate.
- the first described crystal form referred to as form A, has a melting point of 184 ⁇ 4EC and is described as being essentially water free and as such having a water content of ⁇ 0.2% by weight.
- the second described crystal form referred to as form B, has a melting point of 145 ⁇ 3EC and has a water content of 3.4% by weight and is described as the monohydrate.
- the preparation of the monohydrate form B from amlodipine free base is described in Example 2.
- amlodipine such as for example, amlodipine mesylate monohydrate
- the monohydrate can exhibit advantageous stability and non-hygroscpic properties, and as such can also exhibit good handling properties.
- amlodipine mesylate monohydrate which process comprises preparing amlodipine mesylate monohydrate either from anhydrous amlodipine mesylate, or in the presence of a water immiscible solvent medium from amlodipine free base and methane sulphonic acid.
- a process according to the present invention comprises dissolving anhydrous amlodipine mesylate in a water miscible solvent medium, and crystallising amlodipine mesylate monohydrate therefrom.
- the water miscible solvent medium can comprise one or more lower alcohols, such as any of C 1-3 alcohols.
- methanol may be employed in the water miscible solvent medium.
- the use of methanol can be particularly desirable as it can yield highly pure, stable, white crystalline amlodipine mesylate monohydrate.
- a process according to the present invention comprises exposing anhydrous amlodipine mesylate to an atmosphere saturated with moisture so as to yield amlodipine mesylate monohydrate.
- amlodipine mesylate monohydrate is prepared from amlodipine free base
- the water immiscible solvent medium comprises ethylether, ethylacetate, dichloromethane or the like, preferably ethyl acetate.
- a first reaction mixture comprising amlodipine free base dissolved in the water immiscible solvent medium, typically ethyl acetate, is prepared, a second reaction mixture comprising methane sulphonic acid dissolved in a water immiscible solvent medium, again typically ethyl acetate, is prepared, and the first and second reaction mixtures are contacted under conditions to yield amlodipine mesylate monohydrate.
- Figure 1 shows a DSC thermogram of amlodipine mesylate monohydrate as obtained by the following Examples 1, 2 and 3.
- amlodipine mesylate 25g was dissolved in a mixture of methanol 50ml and isopropanol 250ml at 50EC and the resulting solution was filtered under nitrogen. The clear filtrate was cooled to 10EC and the resulting crystals filtered. The material was dried under vacuum at 35EC for 4 hours to give amlodipine mesylate monohydrate 22.4g. The water content was about 3.5%.
- amlodipine mesylate was exposed to an atmosphere saturated with moisture for 2 to 4 hours. Amlodipine mesylate monohydrate was unloaded and the moisture content thereof was about 3.4%.
- Amlodipine free base (25gms) was dissolved in ethyl acetate (300ml) at room temperature. 6.25gms of methane sulphonic acid was separately dissolved in 250ml of ethyl acetate. The amlodipine free base solution was cooled to 20EC under a nitrogen blanket and the clear methane sulphonic acid solution was added. The reaction mass was stirred for 1 hour and filtered. The material was dried under vacuum and nitrogen, to yield amlodipine mesylate monohydrate having a moisture content of about 3.32%.
- phthaloyl amlodipine 100 grams is stirred in a mixture of 40% aqueous monomethylamine (700 ml) and dichloromethane (500ml) at ambient temperature for 12 hours. After reaction completion, the dichloromethane layer is separated and the organic layer is washed with water. The dichloromethane layer is dried over sodium sulfate and distilled to about half the original volume. Ethyl acetate (1000 ml) is added and the distillation continued till a total volume of 600 ml is left behind. The contents are then cooled to 25 - 30°C.
- Methane sulfonic acid (18 gm) is dissolved in 100 ml of ethyl acetate and is added to the above solution in 30 - 45 mins. at 20 - 25°C maintaining an inert atmosphere. Then the contents are stirred for 1 hour at 0 - 5 °C for 30 mins and filtered to give amlodipine mesylate monohydrate 60 gm.
- phthaloyl amlodipine 100 grams is stirred in 20% methanolic monomethylamine (1000 ml.) for 12 hours at room temperature. After reaction completion, the reaction mass is distilled to half of its original volume and 800 ml of dichloromethane is added and further distilled till a total of 500 ml remains in the reaction flask. The dichloromethane layer is washed with water and dried over sodium sulfate. The dichloromethane layer is distilled to half the original volume. 1000 ml ethyl acetate is added and further distilled till 600ml of solution is retained. The contents are then cooled to 25 - 30°C.
- amlodipine mesylate 25 gm was dissolved in a mixture of methanol 25 ml isopropanol 250 ml and water 2.5 ml at 50EC and the resulting solution was filtered under nitrogen. The clear filtrate was cooled to 10EC and the resulting crystals filtered. The material was dried under vacuum at 35EC for 4 hours to give amlodipine mesylate monohydrate 21.8 gm. The water content was about 3.5%.
- amlodipine mesylate 25 gm was dissolved in ethyl acetate 300 ml at 50EC. Methanol 20 ml and water 5 ml were added and the resulting solution was filtered under nitrogen. The clear filtrate was cooled to 10EC and the resulting crystals filtered. The material was dried under vacuum at 35EC for 4 hours to give amlodipine mesylate monohydrate. The water content was about 3.6%.
- amlodipine mesylate 50 gm was dissolved in methanol 150 ml and water 20 ml. Methanol was distilled off and simultaneously replaced with an equal quantity of acetone. When crystals began to appear, the distillation was stopped and the contents cooled to 10°C and the crystals filtered. The material was dried under vacuum at 35EC for 4 hours to give amlodipine mesylate monohydrate 43 gm. The water content was about 3.4%.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Amlodipine mesylate monohydrate is prepared either from anhydrous amlodipine mesylate, or in the presence of a water immiscible solvent medium from amlodipine free base and methane sulphonic acid.
Description
PROCESS FOR PREPARING ALMODI PINE MESYLATE MONOHYDRATE
The present invention is concerned with a process for preparing amlodipine mesylate monohydrate.
Amlodipine is the international non-proprietary name of 2-[(2-Aminoethoxy)- methyl]-4-(2-chlorophenyl)-l,4-dihydro-6-methyl-3,5-pyridinecarboxylic acid 3-ethyl 5- methyl ester. Amlodipine is known to be a calcium channel blocker and has therapeutic applications in the treatment or prevention of a number of cardiac conditions, such as angina pectoris, cardiac arrythmias, heart attacks, cardiac hypertrophy and related cardiac conditions, and also as an antihypertensive agent, for example in the treatment of coronary vasospasm.
Amlodipine is the title compound of Example 9 of European Patent 0089167B and its preparation is described therein. European Patent 0089167B describes suitable pharmaceutically acceptable salts of the compounds described therein, including the hydrochloride, hydrobromide, sulphate, phosphate or acid phosphate, acetate, maleate, fumarate, lactate, tartrate, citrate and gluconate salts. Maleate is described as the preferred salt. The preparation of the maleate salt of amlodipine is described in Examples 11 and 12 of European Patent 0089167B.
European Patent Application 0244944A describes further salts of amlodipine, and describes the besylate salt of amlodipine as being a particularly preferred salt.
US Patent 6057344 describes the use of (-)amlodipine, substantially free of its (+) stereoisomer, in eliciting an antihypertensive effect and also for use in the treatment of angina. Preferred pharmaceutically acceptable salts described in US Patent 6057344 are derived from besylate, hydrobromic, hydrochloric, phosphoric and sulphuric acids.
US Patent Application 2002/0045648 describes a pharmaceutical composition comprising an NO-releasing amount of the R(+)enantiomer of amlodipine or of a pharmaceutically acceptable salt thereof, an antihypertensive amount of the S(-) enantiomer of amlodipine or of a pharmaceutically acceptable salt thereof and a suitable excipient, diluent or carrier, wherein the enantiomers are present in a ratio by weight (based on free base) of R(+)enantiomer: S(-)enantiomer of greater than 1:1.
European patent application 1221438 A describes the preparation of two different crystalline forms of amlodipine mesylate. The first described crystal form, referred to as form A, has a melting point of 184±4EC and is described as being essentially water free and as such having a water content of <0.2% by weight. The second described crystal form, referred to as form B, has a melting point of 145±3EC and has a water content of 3.4% by weight and is described as the monohydrate. The preparation of the monohydrate form B from amlodipine free base is described in Example 2.
The provision of a monohydrate form of amlodipine, such as for example, amlodipine mesylate monohydrate, can be desirable as the monohydrate can exhibit advantageous stability and non-hygroscpic properties, and as such can also exhibit good handling properties. We have now developed an improved process of preparing amlodipine mesylate monohydrate, which can yield a highly pure and stable product.
More particularly, there is provided by the present invention a process for preparing amlodipine mesylate monohydrate, which process comprises preparing amlodipine mesylate monohydrate either from anhydrous amlodipine mesylate, or in the presence of a water immiscible solvent medium from amlodipine free base and methane sulphonic acid.
In a first aspect of the present invention wherein amlodipine mesylate monohydrate is prepared from anhydrous amlodipine mesylate, a process according to the present invention comprises dissolving anhydrous amlodipine mesylate in a water miscible solvent medium, and crystallising amlodipine mesylate monohydrate therefrom.
Suitably the water miscible solvent medium can comprise one or more lower alcohols, such as any of C1-3 alcohols. Preferably methanol may be employed in the water miscible solvent medium. The use of methanol can be particularly desirable as it can yield highly pure, stable, white crystalline amlodipine mesylate monohydrate.
In a second aspect according to the present invention wherein amlodipine mesylate monohydrate is again prepared from anhydrous amlodipine mesylate, a process according to the present invention comprises exposing anhydrous amlodipine mesylate to an atmosphere saturated with moisture so as to yield amlodipine mesylate monohydrate.
In a third aspect according to the present invention wherein amlodipine mesylate monohydrate is prepared from amlodipine free base, suitably the water immiscible
solvent medium comprises ethylether, ethylacetate, dichloromethane or the like, preferably ethyl acetate. It is also generally preferred that a first reaction mixture comprising amlodipine free base dissolved in the water immiscible solvent medium, typically ethyl acetate, is prepared, a second reaction mixture comprising methane sulphonic acid dissolved in a water immiscible solvent medium, again typically ethyl acetate, is prepared, and the first and second reaction mixtures are contacted under conditions to yield amlodipine mesylate monohydrate.
The present invention will now be illustrated by the following Examples which do not limit the scope of the invention in any way.
Figure 1 shows a DSC thermogram of amlodipine mesylate monohydrate as obtained by the following Examples 1, 2 and 3.
Example 1
Anhydrous amlodipine mesylate 25g was dissolved in a mixture of methanol 50ml and isopropanol 250ml at 50EC and the resulting solution was filtered under nitrogen. The clear filtrate was cooled to 10EC and the resulting crystals filtered. The material was dried under vacuum at 35EC for 4 hours to give amlodipine mesylate monohydrate 22.4g. The water content was about 3.5%.
Example 2
Anhydrous amlodipine mesylate was exposed to an atmosphere saturated with moisture for 2 to 4 hours. Amlodipine mesylate monohydrate was unloaded and the moisture content thereof was about 3.4%.
Example 3
Amlodipine free base (25gms) was dissolved in ethyl acetate (300ml) at room temperature. 6.25gms of methane sulphonic acid was separately dissolved in 250ml of ethyl acetate. The amlodipine free base solution was cooled to 20EC under a nitrogen blanket and the clear methane sulphonic acid solution was added. The reaction mass was stirred for 1 hour and filtered. The material was dried under vacuum and nitrogen, to yield amlodipine mesylate monohydrate having a moisture content of about 3.32%.
Example 4
100 grams of phthaloyl amlodipine is stirred in a mixture of 40% aqueous monomethylamine (700 ml) and dichloromethane (500ml) at ambient temperature for 12 hours. After reaction completion, the dichloromethane layer is separated and the organic layer is washed with water. The dichloromethane layer is dried over sodium sulfate and distilled to about half the original volume. Ethyl acetate (1000 ml) is added and the distillation continued till a total volume of 600 ml is left behind. The contents are then cooled to 25 - 30°C.
Methane sulfonic acid (18 gm) is dissolved in 100 ml of ethyl acetate and is added to the above solution in 30 - 45 mins. at 20 - 25°C maintaining an inert atmosphere. Then the contents are stirred for 1 hour at 0 - 5 °C for 30 mins and filtered to give amlodipine mesylate monohydrate 60 gm.
Example 5
100 grams of phthaloyl amlodipine is stirred in 20% methanolic monomethylamine (1000 ml.) for 12 hours at room temperature. After reaction completion, the reaction mass is distilled to half of its original volume and 800 ml of dichloromethane is added and further distilled till a total of 500 ml remains in the reaction flask. The dichloromethane layer is washed with water and dried over sodium sulfate. The dichloromethane layer is distilled to half the original volume. 1000 ml ethyl acetate is added and further distilled till 600ml of solution is retained. The contents are then cooled to 25 - 30°C.
18 gm of methane sulfonic acid dissolved in 100 ml of ethyl acetate is added to the above solution in 30 - 45 mins. at 20 - 25°C under an inert atmosphere. 100 ml methanol and 10 ml purified water are added and warmed to 40 - 45°C. The contents are then stirred at 25 - 30°C for 1 hour, cooled and filtered to give amlodipine mesylate monohydrate 55 gm.
Example 6
Anhydrous amlodipine mesylate 25 gm was dissolved in a mixture of methanol 25 ml isopropanol 250 ml and water 2.5 ml at 50EC and the resulting solution was filtered
under nitrogen. The clear filtrate was cooled to 10EC and the resulting crystals filtered. The material was dried under vacuum at 35EC for 4 hours to give amlodipine mesylate monohydrate 21.8 gm. The water content was about 3.5%.
Example 7
Anhydrous amlodipine mesylate 25 gm was dissolved in ethyl acetate 300 ml at 50EC. Methanol 20 ml and water 5 ml were added and the resulting solution was filtered under nitrogen. The clear filtrate was cooled to 10EC and the resulting crystals filtered. The material was dried under vacuum at 35EC for 4 hours to give amlodipine mesylate monohydrate. The water content was about 3.6%.
Example 8
Anhydrous amlodipine mesylate 50 gm was dissolved in methanol 150 ml and water 20 ml. Methanol was distilled off and simultaneously replaced with an equal quantity of acetone. When crystals began to appear, the distillation was stopped and the contents cooled to 10°C and the crystals filtered. The material was dried under vacuum at 35EC for 4 hours to give amlodipine mesylate monohydrate 43 gm. The water content was about 3.4%.
Claims
CLAIMS:
1 A process for preparing amlodipine mesylate monohydrate, which process comprises preparing amlodipine mesylate monohydrate either from anhydrous amlodipine mesylate, or in the presence of a water immiscible solvent medium from amlodipine free base and methane sulphonic acid.
2 A process according to claim 1, which comprises dissolving anhydrous amlodipine mesylate in a water miscible solvent medium, and crystallising amlodipine mesylate monohydrate therefrom.
3 A process according to claim 2, wherein the water miscible solvent medium comprises one or more lower alcohols.
4 A process according to claim 3, wherein the water miscible solvent medium comprises one or more C1-3alcohols.
5 A process according to claim 4, wherein the water miscible solvent medium comprises methanol.
6 A process according to claim 1, which process comprises exposing anhydrous amlodipine mesylate to an atmosphere saturated with moisture so as to yield amlodipine mesylate monohydrate.
7 A process according to claim 1, wherein said water immiscible solvent medium comprises ethyl acetate
8 A process according to claim 1, wherein a first reaction mixture comprising amlodipine free base dissolved in said water immiscible solvent medium is prepared, a second reaction mixture comprising methane sulphonic acid dissolved in a water immiscible solvent medium is prepared, and the first and second reaction mixtures are contacted under conditions to yield amlodipine mesylate monohydrate.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE112004000712T DE112004000712T5 (en) | 2003-04-25 | 2004-04-16 | Process for the preparation of amlodipine mesylate monohydrate |
| GB0522075A GB2415696B (en) | 2003-04-25 | 2004-04-16 | Process for preparing amlodipine mesylate monohydrate |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0309471.1 | 2003-04-25 | ||
| GB0309471A GB0309471D0 (en) | 2003-04-25 | 2003-04-25 | Process |
| GB0314617.2 | 2003-06-23 | ||
| GB0314617A GB0314617D0 (en) | 2003-06-23 | 2003-06-23 | Process |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2004096770A1 true WO2004096770A1 (en) | 2004-11-11 |
Family
ID=33420880
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB2004/001638 Ceased WO2004096770A1 (en) | 2003-04-25 | 2004-04-16 | Process for preparing almodipine mesylate monohydrate |
Country Status (6)
| Country | Link |
|---|---|
| AR (1) | AR044063A1 (en) |
| CL (1) | CL2004000864A1 (en) |
| DE (1) | DE112004000712T5 (en) |
| GB (1) | GB2415696B (en) |
| PA (1) | PA8601501A1 (en) |
| WO (1) | WO2004096770A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1458681A4 (en) * | 2001-11-22 | 2005-04-27 | Xitian Zhang | Hydrophilic (s)-amlodipine salts or their hydrates and pharmaceutical compositions |
| CN112538044A (en) * | 2019-12-09 | 2021-03-23 | 昆明赛诺制药股份有限公司 | Amlodipine mesylate monohydrate, and preparation method and application thereof |
| WO2021114012A1 (en) * | 2019-12-09 | 2021-06-17 | 昆明赛诺制药股份有限公司 | Amlodipine mesylate monohydrate, preparation method therefor and use thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0089167A2 (en) * | 1982-03-11 | 1983-09-21 | Pfizer Limited | Dihydropyridine anti-ischaemic and antihypertensive agents, processes for their production, and pharmaceutical compositions containing them |
| EP0244944A2 (en) * | 1986-04-04 | 1987-11-11 | Pfizer Limited | Salts of amlodipine |
| EP1221438A2 (en) * | 2001-01-09 | 2002-07-10 | Siegfried Ltd. | Amlodipine mesylate salts |
-
2004
- 2004-04-16 WO PCT/GB2004/001638 patent/WO2004096770A1/en not_active Ceased
- 2004-04-16 GB GB0522075A patent/GB2415696B/en not_active Expired - Fee Related
- 2004-04-16 DE DE112004000712T patent/DE112004000712T5/en not_active Withdrawn
- 2004-04-22 AR ARP040101372A patent/AR044063A1/en unknown
- 2004-04-23 CL CL200400864A patent/CL2004000864A1/en unknown
- 2004-04-23 PA PA20048601501A patent/PA8601501A1/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0089167A2 (en) * | 1982-03-11 | 1983-09-21 | Pfizer Limited | Dihydropyridine anti-ischaemic and antihypertensive agents, processes for their production, and pharmaceutical compositions containing them |
| EP0244944A2 (en) * | 1986-04-04 | 1987-11-11 | Pfizer Limited | Salts of amlodipine |
| EP1221438A2 (en) * | 2001-01-09 | 2002-07-10 | Siegfried Ltd. | Amlodipine mesylate salts |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1458681A4 (en) * | 2001-11-22 | 2005-04-27 | Xitian Zhang | Hydrophilic (s)-amlodipine salts or their hydrates and pharmaceutical compositions |
| CN112538044A (en) * | 2019-12-09 | 2021-03-23 | 昆明赛诺制药股份有限公司 | Amlodipine mesylate monohydrate, and preparation method and application thereof |
| WO2021114012A1 (en) * | 2019-12-09 | 2021-06-17 | 昆明赛诺制药股份有限公司 | Amlodipine mesylate monohydrate, preparation method therefor and use thereof |
| CN112538044B (en) * | 2019-12-09 | 2021-08-13 | 昆明赛诺制药股份有限公司 | Amlodipine mesylate monohydrate, and preparation method and application thereof |
| US12435038B2 (en) | 2019-12-09 | 2025-10-07 | Kunming Sinoway Natural Pharmaceuticals Co., Ltd. | Amlodipine mesylate monohydrate preparation method therefor and use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| GB2415696B (en) | 2007-06-20 |
| AR044063A1 (en) | 2005-08-24 |
| GB2415696A (en) | 2006-01-04 |
| PA8601501A1 (en) | 2004-12-16 |
| CL2004000864A1 (en) | 2005-04-22 |
| DE112004000712T5 (en) | 2006-10-19 |
| GB0522075D0 (en) | 2005-12-07 |
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