Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1997-09-17
1999-05-04
Rose, Shep K.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
424451, 424457, 424464, 424468, A61K 920, A61K 922, A61K 948, A61K 952
Patent
active
059004312
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a novel use of fumagillol and its derivatives, especially fimagillin.
Fumagillin is an antibiotic, first described in 1951 (The Merck Index 11th Edition, no. 4199), which is used especially for preventing or controlling parasitic diseases in fish farming and beekeeping and which has also been used in man for the local treatment, in an eye lotion, of keratoconjunctivitis due to Encephalitozoon hellem (J. Ophtal., 1993, 115, 293). However, it has been found to be inactive as a carcinolytic agent (Antibiotic Annual, 1958-1959, 541-546).
It has now been found that fumagillol and certain esters formed with this compound, when formulated in a drug, especially an oral drug, are capable of resolving very serious infectious conditions of the intestine due to microsporidia or cryptosporidia.
It has also been found, surprisingly, that fuimagillol and the esters formed by fumagillol and saturated or unsaturated (C.sub.1 -C.sub.12) alkylcarboxylic or (C.sub.1 -C.sub.12) alkyldicarboxylic acids are capable of inducing eradication of Enterocytozoon bieneusi in patients affected by HIV. This discovery is surprising and decisive because there is currently no known remedy for this type of infection, which constitutes 95% of the intestinal infections due to microsporidia which result in cachexia and death in patients suffering from AIDS.
Thus, according to one of its features, the present invention relates to the use of fumagillol or esters formed by fuimagillol and saturated or unsaturated (C.sub.1 -C.sub.12) alkylcarboxylic or (C.sub.1 -C.sub.12) alkyldicarboxylic acids, and their pharmaceutically acceptable salts, for the preparation of drugs for combating intestinal infections due to microsporidia and/or cryptosporidia.
More particularly and advantageously, according to its preferred feature, the present invention relates to the use of fumagillol or esters formed by fumagillol and saturated or unsaturated (C.sub.1 -C.sub.12) alkylcarboxylic or (C.sub.1 -C.sub.12) alkyldicarboxylic acids, and their pharmaceutically acceptable salts, for the preparation of drugs for combating intestinal infections for which the parasite Enterocytozoon bieneusi is principally responsible.
"Saturated or unsaturated (C.sub.1 -C.sub.12) alkylcarboxylic or (C.sub.1 -C.sub.12) alkyldicarboxylic acids" are understood as meaning carboxylic or dicarboxylic acids of linear or branched alkyls, it being possible for said alkyls to contain one or more double bonds.
Examples of such acids are acetic, propionic, butyric, valeric, pivalic, malonic, succinic, acrylic, crotonic, isocrotonic, oleic, maleic, fumaric and 2,4,6,8-decatetraenedioic acids.
The ester of fumagillol and 2,4,6,8-decatetraenedioic acid, fumagillin, is a particularly advantageous compound.
The esters of the present invention are easily prepared by reacting fumagillol with the appropriate acid under the normal esterification conditions described in the literature.
Fumagillol, either as such or esterified with a (C.sub.1 -C.sub.12) alkylcarboxylic or (C.sub.1 -C.sub.12) alkyldicarboxylic acid, can be administered in the form of the free acid or else in the form of one of its salts with a pharmaceutically acceptable base.
For their administration to patients suffering from an infection due to microsporidia or cryptosporidia, fumagillol or the esters formed therewith are mixed with pharmaceutical excipients commonly used for the preparation of pharmaceutical formulations, preferably for oral administration.
Advantageously, the compounds of the present invention are formulated as active principles in dosage units, for example tablets or gelatin capsules, containing from 1 to 200 mg of active principle, advantageously from 2 to 100 mg, more advantageously from 5 to 50 mg or preferably from 7.5 to 30 mg per dosage unit.
The pharmaceutical compositions for oral administration constitute a further subject of the present invention.
In the pharmaceutical compositions of the present invention for oral administration, the active principle can be administered in the
REFERENCES:
patent: 2791530 (1957-05-01), Dallavis et al.
patent: 5328930 (1994-07-01), Wilson
Molina et al AIDS (London) 11(13):1603-1610, 1997.
Derouin Francis
Molina Jean-Michel
Rose Shep K.
Sanofi
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