Pseudopolymorphic forms of...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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Details

C544S396000

Reexamination Certificate

active

06262057

ABSTRACT:

The present invention relates to new pseudopolymorphic crystalline forms of 2-[2-[4-[bis(4-fluorophenyl)methyl]-1-piperazinyl]ethoxy]acetic acid dihydrochloride, to processes for their preparation and to pharmaceutical compositions containing them.
2-[2-[4-[Bis(4-fluorophenyl)methyl]-1-piperazinyl]ethoxy]acetic acid, also known and hereinafter referred to as efletirizine (INN: International Non-proprietary Name), is the compound of the following formula:
Efletirizine is encompassed within general formula I of European patent No. 58146 in the name of the applicant, which relates to substituted benzhydrylpiperazine derivatives.
Like 2-[2-[4-1(4-chlorophenyl)phenylmethyl]-1-piperazinyl]ethoxy]acetic acid, also known and hereinafter referred to as cetirizine (INN), efletirizine has been found to possess excellent antihistaminic properties. It belongs to the pharmacological class of second generation histamine H
1
-receptor antagonists and shows in vitro high affinity and selectivity for H
1
-receptors. Like cetirizine, it is useful as an antiallergic, antihistaminic, bronchodilator and antispasmodic agent. Recent clinical studies have shown the utility of efletirizine when administered in the form of a nasal spray for the treatment of allergic rhinitis and rhino-conjunctivitis (J. -F. Dessanges et al., Allergy and Clin. Immunol. News (1994), Suppl. n°2, abstract 1864; C. De Vos et al., Allergy and Clin. Immunol. News (1994), Suppl. n°2, abstract 428).
Another recent clinical pharmacology study (to be published) has shown that efletirizine gives unexpectedly good results In the treatment of urticaria, atopic dermatitis and prurit.
Due to increasing therapeutic interest for efletirizine, we have set out to prepare pharmaceutical compositions containing efletirizine.
Efletirizine is an amorphous solid. However, it is highly desirable to dispose of a product with reproducible characteristics, which always performs in the same way during formulation. in particular in order to comply with regulatory requirements. For these reasons, we attempted to prepare crystalline forms of efletirizine. Although efletirizine has been studied for its therapeutic utility, no attention has yet been given to such crystalline forms.


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patent: 97/2973 (1998-01-01), None

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