IPC분류정보
국가/구분 |
United States(US) Patent
등록
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국제특허분류(IPC7판) |
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출원번호 |
US-0685033
(1976-05-10)
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발명자
/ 주소 |
- Berg David H. (Greenfield IN) Hamill Robert L. (Greenwood IN) Hoehn Marvin M. (Indianapolis IN)
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출원인 / 주소 |
- Eli Lilly and Company (Indianapolis IN 02)
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인용정보 |
피인용 횟수 :
7 인용 특허 :
0 |
초록
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Antibiotic A-28086 complex, comprising microbiologically active, structurally related factors A, B, and D, produced by submerged aerobic fermentation of Streptomyces aureofaciens NRRL 5758. Individual factors A, B, and D are separated and isolated by chromatography. The A-28086 antibiotics are antib
Antibiotic A-28086 complex, comprising microbiologically active, structurally related factors A, B, and D, produced by submerged aerobic fermentation of Streptomyces aureofaciens NRRL 5758. Individual factors A, B, and D are separated and isolated by chromatography. The A-28086 antibiotics are antibacterial, antifungal, antiviral, anti-PPLO, anticoccidial, insecticidal and acaricidal agents and also increase feed-utilization efficiency in ruminants.
대표청구항
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A method of preventing or treating coccidiosis in poultry which comprises administering to poultry an effective anticoccidial amount of a composition comprising a physiologically-acceptable carrier and a compound selected from the group consisting of antibiotic A-28086 factor A which is a white crys
A method of preventing or treating coccidiosis in poultry which comprises administering to poultry an effective anticoccidial amount of a composition comprising a physiologically-acceptable carrier and a compound selected from the group consisting of antibiotic A-28086 factor A which is a white crystalline compound when crystallized from acetone-water; which is soluble in lower alcohols, dimethylformamide, dimethyl sulfoxide, ethyl acetate, chloroform, acetone, and benzene; but which is only slightly soluble in hexane; and is insoluble in water; which melts at about 98°-100°C., resolidifies, and remelts at about 195°-200°C. and which has: (a) a molecular weight of 764, as determined by mass spectrometry; (b) an approximate elemental composition of 66.69 percent carbon, 9.85 percent hydrogen, and 23.10 perCent oxygen; (c) an empirical formula of C43H72O11, as determined by mass spectrometry; (d) a specific rotation of -54°(c=0.2, methanol) when determined at 25°C.; (e) an infrared absorption spectrum in chloroform with the following distinguishable absorption maxima: 2.85, 3.34, 5.83, 6.82, 7.22, 7.53 (weak), 7.78 (weak), 8.75 (strong), 8.95 (strong), 9.15, 9.50 (strong), 9.55 (strong), 9.60, 9.85, 10.15, 10.45, and 10.70 (weak) microns; (f) in its ultraviolet spectrum in ethanol only end absorption below 220 mmd6.01, 4.21, 4.11, 3.99, 3.89, 3.80, 3.67, 3.65, 3.57, 3.55, 2.83, 2.76, 2.74, 2.68, 2.66, 2.58, 2.56, 2.30, 2.22, 2.17, 2.10, 2.05, 1.96, 1.90, 1.85, 1.70, 1.62, 1.60, 1.47, 1.39, 1.31, 1.25, 1.18, 0.95, 0.93, 0.90, 0.88, 0.85, 0.77, 0.75, 0.73, 0.68, and 0.66 ppm; (h) a titratable group with a pKa value of 7.9 in 80% aqueous dimethylformamide; (i) a characteristic X-ray powder diffraction pattern (Curadiation, 1.5405 lnickel filter) having the following interplanar spacings in angstroms (d): ________________________________ -d Relative Intensity ________________________________ 12.00 100 10.10 50 9.25 90 8.00 40 7.50 15 6.92 90 6.40 40 5.98 05 5.68 15 5.20 40 4.98 40 4.62 40 4.21 20 3.48 10 ________________________________ (j) Rf value of 0.24 on thin-layer chromatography over silica gel in a benzene-ethyl acetate (3:2) solvent system, using Bacillus subtilis ATCC 6633 as the detection organism; (k) the following Rf values in the paper-chromatographic systems indicated below, using Bacillus subtilis ATCC 6633 as detection organism: ________________________________ -RfValue Solvent System ________________________________ 0.11 Water saturated with methyl iso- butyl ketone (MIBK) 0.41 Water saturated with MIBK plus 2% p-toluenesulfonic acid and 1% piperidine 0.54 Water:methanol:acetone (12:3:1)- adjusted to pH 10.5 with NH4OH and then lowered to pH 7.5 with H3PO4 0.48 1% MIBK, 0.5% NH4OH in water 0.15 17.4 g K2HPO4, 30 ml ethanol per liter of water 0.24 Benzene saturated with water 0.24 Water 0.75 Water:MIBK:ethyl acetate (98:1:1) ________________________________ (l) an acid function capable of forming salts and ester derivatives; and (m) at least one hydroxyl group capable of esterification; A-28086 factor A acetyl ester derivative which is a white crystalline compound (from acetone-water); which is soluble in methanol, ethanol, dimethylformamide, dimethyl sulfoxide, ethyl acetate, chloroform, acetone and benzene; is only slightly soluble in hexane; and is insoluble in water; which melts at about 100°-103°C.; and which has: (a′) a molecular weight of about 807; (b′) an elemental composition of 67.67 percent carbon, 8.71 percent hydrogen, and 23.13 percent oxygen; (c′) an empirical formula of C45H74O12; (d′) an infrared spectrum in chloroform with the following observable absorption maxima: 2.85, 3.36, 3.38 (strong), 5.80, 6.83, 7.25, 7.52 (strong), 7.60 (weak), 7.80 (strong), 8.45 (strong), 8.80 (strong), 8.95 (strong), 9.10 (strong), 9.20, 9.63, 9.80 (strong), 10.12 (weak), 10.25 (weak), and 10.50 microns; (e′) an ultraviolet spectrum showing only end absorption; (f′) a nuclear magnetic resonance spectrum in which the carbinyl resonance is shifted downfield to approximately 5.3 ppm; (g′) a titratable group with a pKa value of 8.5 in 80% aqueous dimethylformamide; (h′) an acid function capable of forming salts and ester derivatives; A-28086 factor A propionyl ester derivative which is a white crystalline compound (from acetone-water); which is soluble in methanol, ethanol, dimethylformamide, dimethyl sulfoxide, ethyl acetate, chloroform, acetone, and benzene; is slightly soluble in hexane; and is insoluble in water; which melts at about 96°-98°C.; and which has: (a″) a molecular weight of about 821; (b″) an elemental composition of 66.06 percent carbon, 9.17 percent hydrogen, and 23.41 percent oxygen; (c″) an empirical formula of C46H76O12; (d″) an infrared absorption spectrum in chloroform with the following observable absorption maxima: 2.85, 3.33, 3.38 (strong), 3.45 (strong), 5.75 (strong), 5.82, 6.81, 7.22, 7.30 (strong), 7.50 (weak), 7.60 (weak), 7.80, 8.43, 8.75 (strong), 8.90, 9.05, 9.15 (strong), 9.50 (strong), 9.63, 9.83 (weak), 10.05 (strong), 10.13, 10.20 (strong), 10.45, and 10.68 microns; (e″) an ultraviolet spectrum showing only end absorption; (f″) a nuclear magnetic resonance spectrum in which the carbinyl resonance is shifted downfield to approximately 5.3 ppm; (g″) an acid function capable of forming salts and ester derivatives; A-28086 factor A butyryl ester derivative which is a white crystalline compound (from acetone-water); which is soluble in methanol, ethanol, dimethylformamide, dimethyl sulfoxide, ethyl acetate, chloroform, acetone, and benzene; is slightly soluble in hexane; and is insoluble in water; which melts about 96°-98°C.; and which has: (a′″) a molecular weight of about 835; (b′″) an approximate elemental composition of 67.60 percent carbon, 9.41 percent hydrogen, and 22.99 percent oxygen; (c′″) an empirical formula of C47H78O12; (d′″) an infrared spectrum in chloroform with the following observable absorption maxima: 2.89, 3.40, 3.45, 3.51, 5.85, 5.92 (strong), 5.97 (strong), 6.90, 7.30, 7.84 (weak), 8.55, 8.85 (weak), 9.01 (strong), 9.26, 9.76, 9.95, 10.31, and 10.64 microns; (e′″) a nuclear magnetic resonance spectrum in which the carbinyl resonance is shifted downfield to approximately 5.3 ppm; (f′″) an acid function capable of forming salts and ester derivatives; A-28086 factor A valeryl ester derivative which is a white crystalline compound (from acetone-water); which is soluble in methanol, ethanol, dimethylformamide, dimethyl sulfoxide, ethyl acetate, chloroform, acetone, and benzene; is slightly soluble in hexane; and is insoluble in water; which melts at about 173°-175°C.; and which has: (a″″) a molecular weight of about 849; (b″″) an approximate elemental composition of 67.89 percent carbon; 9.50 percent hydrogen; and 22.61 percent oxygen; (c″″) an empirical formula of C48H80O12; (d″″) an infrared spectrum in chloroform with the following observable absorption maxima: 2.90, 3.40, 3.45, 3.51, 5.87, 5.92 (strong), 5.99 (strong), 6.91, 7.30, 7.69 (weak), 7.87 (weak), 8.16, 8.58, 8.85 (weak), 9.26, 9.76, 10.00 (weak), 10.31, and 10.64 microns; (e″″) a nuclear magnetic resonance spectrum in which the carbinyl resonance is shifted downfield to approximately 5.3 ppm; (f″″) an acid function capable of forming salts and ester derivatives; A-28086 factor A caproyl ester derivative which is a white crystalline compound (from acetone-water); which is soluble in methanol, ethanol, dimethylformamide, dimethyl sulfoxide, ethyl acEtate, chloroform, acetone, and benzene; is slightly soluble in hexane; and is insoluble in water; which melts at about 163°-167°C.; and which has: (a′″″) a molecular weight of about 863; (b′″″) an approximate elemental composition of 68.18 percent carbon; 9.58 percent hydrogen; and 22.24 percent oxygen; (c′″″) an empirical formula of C49H82O12; (d′″″) an infrared spectrum in chloroform with the following observable absorption maxima: 2.90, 3.40, 3.45, 3.51, 5.87, 5.92 (strong), 5.97 (strong), 6.90, 7.30, 7.66 (weak), 7.84 (weak), 8.16, 8.58, 8.85 (weak), 9.05 (strong), 9.17, 9.72, 9.95, 10.29, and 10.62 microns; (e′″″) a nuclear magnetic resonance spectrum in which the carbinyl resonance is shifted downfield to approximately 5.3 ppm; (f′″″) an acid function capable of forming salts and ester derivatives; the pharmaceutically-acceptable salts of A-28086 factor A; antibiotic A-28086 factor B, a white crystalline compound when crystallized from acetone-water, which is soluble in lower alcohols, dimethylformamide, dimethyl sulfoxide, ethyl acetate, chloroform, acetone and benzene; but which is only slightly soluble in hexane and is insoluble in water; and which has: (a) a melting point of about 150°-153°C.; (b) a molecular weight of 762, as determined by high resolution mass spectrometry; (c) an empirical formula of C43H70O11, as determined by high-resolution mass spectrometry; (d) an infrared absorption spectrum in chloroform with the following distinguishable absorption maxima: 2.82, 3.30, 5.77, 5.85, 6.80, 7.20, 7.50 (weak), 7.72 (weak), 7.80 (weak), 8.57 (strong), 8.68, 8.90 (strong), 9.10, 9.50, 9.83 (strong), 9.90, 10.10, 10.17 (strong), 10.43 (weak), 10.80 (weak), 11.20 (weak), 11.35 (weak), 11.73 (weak), and 12.03 (weak) microns; (e) an observed absorption maximum in ethanol in its ultraviolet spectrum at 220 mm1cm1% = 137.5, e); (f) a nuclear magnetic resonance spectrum in deuterochloroform with the following characteristics: d7.20, 7.09, 6.26, 6.15, 4.19, 4.12, 4.05, 3.95, 3.89, 3.78, 3.62, 3.59, 3.52, 3.48, 2.81, 2.73, 2.63, 2.54, 2.52, 1.99, 1.91, 1.84, 1.71, 1.67, 1.64, 1.55, 1.43, 1.33, 1.18, 1.11, 0.96, 0.94, 0.90, 0.87, 0.84, 0.77, 0.74, and 0.68 ppm; (g) an Rf value of 0.42 on thin-layer chromatography over silica gel in benzene-ethyl acetate (3:2), using Bacillus subtilis ATCC 6633 as the detection organism; (h) the following Rf values in the paper-chromatographic systems indicated below, using Bacillus subtilis ATCC 6633 as the detection organism: ________________________________ -RfValue Solvent System ________________________________ 0.16 Water saturated with MIBK plus 2% p-toluenesulfonic acid and 1% piperidine 0.46 Water:methanol:acetone (12:3:1)- adjusted to pH 10.5 with NH4OH and then lowered to pH 7.5 with H3PO4 0.36 1% MIBK, 0.5% NH4OH in water 0.51 Benzene saturated with water 0.11 Water 0.61 Water:MIBK:ethyl acetate (98:1:1) ________________________________ (i) an acid function capable of forming salts and ester derivatives; (j) two ketone moieties; and (k) at least one hydroxyl moiety; and the pharmaceutically-acceptable salts of A-28086 factor B.
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