Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-08-27
2003-03-25
Fan, Jane (Department: 1625)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C546S321000
Reexamination Certificate
active
06538012
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a novel compound, to processes for preparing it and to its use in treating medical disorders. In particular the present invention relates to a novel acid addition salt of amlodipine.
2. Description of the Related Arts
Pharmaceutical products with antianginal and antihypertensive properties are described in U.S. Pat. Nos. 4,572,909 and 4,879,303. An especially important compound among those disclosed is amlodipine, ±2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester. Amlodipine has the following structural formula.
This compound is used for the preparation of a medicament having calcium channel blocking activity, useful in the management of the hypertension and angina pectoris. Particularly useful forms of amlodipine for use in human medicine are maleate and benzenesulfonate salts thereof. Examples 9, 11, 12 and 22 of U.S. Pat. No. 4,572,909 as well as J. Med. Chem. 29,1698(1986) disclose the preparation of amlodipine maleate (in 1:1 molar ratio) by dissolving a reaction mixture containing in situ prepared raw amlodipine base in ethylacetate or in ethanol and adding solid maleic acid while the maleate salt of amlodipine precipitates. The salt is then isolated by filtration and recrystallized from ethyl acetate or from acetone/ethyl acetate 1:1. The prior art disclosure of amlodipine maleate has thus been of a compound having a 1:1 molar ratio between amlodipine and maleic acid. This compound should be more precisely called amlodipine hydrogenmaleate.
SUMMARY OF THE INVENTION
The present invention relates to the discovery of a novel salt of amlodipine useful for the preparation of medicaments containing amlodipine and being a suitable equivalent to the marketed amlodipine benzene sulfonate. Specifically, the present invention relates to amlodipine hemimaleate of formula (1)
Another aspect of the present invention relates to a process that comprises contacting amlodipine free base or a salt thereof with maleic acid or its ammonium salt in the presence of a solvent to form amlodipine hemimaleate.
A further aspect of the present invention relates to a method for treating, or preventing angina or hypertension which comprises administering to a patient in need thereof an effective amount of an amlodipine hemimaleate as well as to a pharmaceutical composition for use in the treatment and/or prevention of angina or hypertension comprising an effective amount of amlodipine hemimaleate together with a pharmaceutically acceptable excipient.
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Fan Jane
Fleshner & Kim LLP
Synthon BV
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