Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1991-11-05
1995-03-21
Rollins, John W.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
514 27, 435101, 435119, 4352521, 536 187, 426658, C07H 1704, A61K 3170, C12P 1900
Patent
active
053996755
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to novel acidic polycyclic ether antibiotics and the pharmaceutically acceptable cationic salts thereof. This invention also relates to novel Actinomadura roseorufa microorganisms. Further, this invention relates to processes for producing the novel acidic polycyclic ether antibiotics and the known acidic polycyclic ether antibiotic UK-58,852. Further still, this invention relates to methods for controlling coccidial infections in poultry, enteritis in livestock and swine dysentery by administering the novel antibiotics of this invention to said animals. This invention also relates to nutrient feed compositions comprising the novel antibiotics of this invention and to methods for promoting growth and/or improving efficiency of feed utilization in ruminant or monogastric animals by administering the novel antibiotics of this invention.
BACKGROUND ART
Acidic polycyclic ether antibotics are a class of compounds characterized by their effects on cation transport in mitochondria. This family of antibiotics includes such well known agents as monensin; nigericin; grisorixin; dianemycin; salinomycin; mutalomycin; ionomycin and leuseramycin. The subject has been reviewed by Westley, "Polyether Antibiotics", Adv. Appl. Microbiol., 22,177, 1977.
The polycyclic ether antibiotics listed immediately above are active against Gram-positive bacteria, fungi and protozoa. In particular those antibiotics exhibit potent anti-coccidial activity. They therefore have been employed with varying degrees of success in the treatment of a variety of animal infections.
The well-known protozoan disease, coccidiosis, continues to be a serious problem and its control is of economic importance to veterinary science, especially to the poultry industry. Coccidiosis results from infection by one or more species of Eimeria or Isospora (for a summary, see Lund and Farr in "Diseases of Poultry," 5th ed., Biester and Schwarte, Eds., Iowa State University Press, Ames, Ia., 1965, pp. 1056-1096). There are six species of coccidia which produce easily discernible morbidity in susceptible chickens. Eimeria tenella, E. necatrix, E. brunetti, E. acervulina, E. maxima and E. mivati produce damage either directly through destruction of epithelial cells of the digestive tract or indirectly through production of toxins. Three other species of protozoa belonging to the same genus are considered to be relatively innocuous; however, E. mitis, E. hagani and E. praecox are capable of reducing weight gain, lowering feed efficiency and adversely affecting egg production.
In view of the great economic losses due to coccidiosis and the known disadvantages of existing anti-coccidial agents, the search for better anti-coccidial agents continues.
Enteritis is another disease which can cause severe economic losses to livestock producers. Enteritis occurs in chickens, swine, cattle and sheep and is attributed mainly to anaerobic bacteria, particularly Clostridium perfringens and viruses. Enterotoxemia in ruminants, an example of which is "overeating disease" in sheep, is a condition caused by C. perfringens infection.
Swine dysentery is one of the most common swine diseases diagnosed in the United States. Additionally, the disease is prevalent in many other countries and annually causes considerable losses in stock to swine growers around the world. It has recently been discovered that a large spirochete is the causative organism of the disease. This organism, Treponema hyodysenteriae, has now been isolated and shown to be capable of producing the disease [Harris, D. L. et al. "Swine-Dysentery-1, Inoculation of Pigs with Treponema hyodysenteriae (New species) and Reproduction of the Disease," Vet Med/SAC, 67, 61-64, 1972]. It must be noted that it is not known whether T. hyodysenteriae is the sole causative organism of swine dysentery. From the data available, however, it can be concluded that it is a primary source of the infection.
Performance enhancement (increased rate of growth and/or increased efficiency of feed utilizatio
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Westley, Adv. Appl. Microbiol. 22:177 (1977).
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Leng in "Physiology of Digestion and Metabolism in the Ruminant," Phillipson et al., Eds., Oriel Press, Newcastle-upon-Tyne, England, 1970, pp. 408-410.
McCullough in "Feedstuffs," Jun. 19, 1971, p. 19.
Church et al. in "Digestive Physiology and Nutrition of Ruminants", vol. 2, 1971, pp. 622 and 625.
"The Merck Veterinary Manual," Siegmund et al., Eds., Merck & Co., Rahway, N.J., 5th Ed., pp. 431-433 (1979).
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Benson Gregg C.
Jones James T.
Lee Howard C.
Pfizer Inc.
Richardson Peter C.
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