Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing heterocyclic carbon compound having only o – n – s,...
Patent
1993-03-12
1995-05-23
Knode, Marian C.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing heterocyclic carbon compound having only o, n, s,...
435123, 4352521, 514451, 514453, 514460, 514462, C12P 1716
Patent
active
054181526
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
The present invention concerns a new acidic polycyclic ether antibiotic having the formula: ##STR1## having relative stereochemistry as shown; pharmaceutically acceptable cationic salts thereof; nutrient feed compositions comprising said antibiotic for poultry, cattle or swine; its use as an anticoccidial agent in poultry, in the treatment or prevention of swine dysentery, or as a growth promotant in cattle or swine; a fermentation method for its preparation; and the Actinomadura sp. microorganism which produces said antibiotic in said fermentation method.
The compound (I) is a new member of the acidic polycyclic ether group of antibiotics. This family includes such well known agents as monensin (The Merck Index, 11th Ed., Merck and Co., Inc., Rahway, N.J., 1989, monograph no. 6157), nigericin (loc. cit., monograph no. 6457), narasin (loc. cit., monograph no. 6339), lasalocid A (loc. cit., monograph no. 5243), and salinomycin (loc. cit., monograph no. 8305). The subject has been reviewed by Westley, "Polyether Antibiotics", Adv. Appl. Microbiol., vol. 22, pp. 177-223 (1977). These compounds are generally known as coccidiostats, as feed additive-growth promotants, and/or as agents useful against swine dysentery.
SUMMARY OF THE INVENTION
A culture of Actinomadura sp. ATCC 55080, when fermented under aerobic conditions in aqueous media, produces a new acidic polycyclic ether antibiotic, a compound having the formula (I), as specified above.
The present invention is directed to said compound of the formula (I), including the pharmaceutically-acceptable cationic salts thereof, and to a process for its preparation which comprises fermentation of said Actinomadura sp. ATCC 55080 in an aqueous nutrient medium comprising an assimilable source of carbon and nitrogen until a recoverable amount of said compound of the formula (I) is formed, preferably under submerged aerobic conditions. For use as an anticoccidial agent, in the prevention or treatment of swine dysentery, and/or as a growth promotant, the compound (I) can be separated from the fermentation and isolated in substantially pure form. However, it is alternatively used in crude form, for example, in precipitated form admixed with mycelium (recovered by filtration of the fermentation medium), or in solids obtained by spray- or freeze-drying the entire fermentation medium.
Said pharmaceutically-acceptable cationic salts include, but are not limited to, those of sodium, potassium, calcium, ammonia, N,N'-dibenzylethylenediamine, N-methylglucamine (meglumine) and diethanoiamine. The preferred cationic salts are those of potassium and sodium.
The present invention is also directed to nutrient feed compositions, one for cattle or swine which comprises the compound of the formula (I) in an amount effective to promote growth and/or improve the feed utilization of said cattle or swine, or to prevent or treat dysentery in swine; and the other for poultry which comprises the compound of the formula (I) in an amount effective to control coccidial infection in said poultry.
The present invention is further directed to a method for promoting growth and/or increasing the efficiency of feed utilization in swine or cattle which comprises administering to said swine or cattle a growth promoting or feed-utilization efficiency promoting amount of the compound of the formula (I), particularly in the form of a nutrient feed composition; to a method for preventing or treating dysentery in swine which comprises administering to said swine a compound of the formula (I) in an amount effective in preventing or treating said dysentery in said swine; and to a method for controlling coccidial infections in poultry which comprises administering to said poultry an anticoccidially effective amount of the compound of the formula (I), particularly in the form of a nutrient feed composition.
Finally, the present invention is directed to a biologically pure culture of Actinomadura sp. ATCC 55080, said culture being capable of producing the compound of the formula
REFERENCES:
patent: 3985872 (1976-10-01), Chamberlin
patent: 4129578 (1978-12-01), Celmer et al.
patent: 4533553 (1985-08-01), Celmer et al.
patent: 4804680 (1989-02-01), Goudie et al.
Waitz et al, The J. of Antibiotics, XXXIV (9):1101-6, (Sep., 1981).
Cullen Walter P.
Dirlam John P.
Maeda Hiroshi
Tone Junsuke
Benson Gregg C.
Knode Marian C.
Osoteo Maria L.
Pfizer Inc
Richardson Peter C.
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