Bleomycin and processes for the preparation thereof
阅读：489发布：2022-09-24
专利汇可以提供Bleomycin and processes for the preparation thereof专利检索，专利查询，专利分析的服务。并且An antibiotic complex designated bleomycin was produced by fermentation of Streptomyces verticillus A.T.C.C. 15003 and found to inhibit the growth of Gram-negative and Gram-positive and acid-fast bacteria as well as certain plant pathogens and to inhibit the growth of HeLa cells in tissue culture and to inhibit the growth of certain experimental tumors in mice.，下面是Bleomycin and processes for the preparation thereof专利的具体信息内容。
2. The process of producing a biologically active complex, identified as bleomycin A, which comprises cultivating Streptomyces verticillus ATTC 15933 at a temperature of about 25* C. to 35* C. for at least 2 days under submerged aerobic conditions in an aqueous assimilable carbohydrate solution containing an assimilable nitrogenous nutrient until the substantial amount of the said antibiotic is produced and then recovering from the broth the bleomycin A thus produced by adsorption on a cation exchange resin and subsequent elution therefrom and then separating the bleomycin A from the bleOmycin B present therewith by chromatography, said bleomycin A being the fraction which exhibits an Rf value of 0.88- 0.94 by paper chromatography using 10% NH4Cl.
3. A biologically active complex identified as bleomycin A which is prepared by the process of claim 2 and which inhibits Gram-positive and Gram-negative bacteria, inhibits Ehrlich carcinoma, is soluble in water and methanol, and practically insoluble in ethanol, butanol, acetone, ethyl acetate, chloroform and benzene, forms salts with acids, chelates with copper, shows two ultraviolet absorption maxima at 254 m Mu and 295 m Mu , gives positive Pauly, Ehrlich, Dragendorf tests, gives negative Sakaguchi, Fehling, Tollens and Molisch tests and shows Rf 0.88-0.94 by paper chromatography using 10% NH5Cl.
4. The process of producing a biologically active substance identified as bleomycin A2 which is one of the main active components of bleomycin A and which gives a negative ninhydrin reaction, gives positive Pauly, Ehrlich, Dragendorf and permanganate tests and negative Sakaguchi, Fehling, Tollens, ferric chloride and Molisch tests, contains C, H. N, S and O and exhibits the ultraviolet absorption spectrum shown in FIG. 3 and the infrared absorption spectrum shown in FIG. 4 after is has been purified as its copper-containing form designated Cu- At2 in said Figures, said process comprising cultivating Streptomyces verticillus ATTC 15003 at a temperature of about 25* C. to 35* C. for at least two days under submerged aerobic conditions in an aqueous assimilable carbohydrate solution containing an assimilable nitrogeneous nutrient until the substantial amount of the said antibiotic is produced and then recovering from the broth the bleomycin A2 thus produced by adsorption on a cation exchange resin and subsequent elution therefrom and then separating the bleomycin A2 from the other bleomycins present therewith by chromatography as the fraction which exhibits in its copper-containing from an Rf of about 0.40 in thin layer chromotography using silica gel and 10 percent ammonium acetate-methanol (1:1) and a negative Sakaguchi reaction.
5. A biologically active substance identified as bleomycin A2 which is prepared by the process of claim 4 and which gives a negative ninhydrin reaction, gives positive Pauly, Ehrlich, Dragendorf and permanganate tests and negative Sakaguchi, Fehling, Tollens, ferric chloride and Molisch tests, contains C, H, N, S and O and exhibits the ultraviolet absorption spectrum shown in FIG. 3 and the infrared absorption spectrum shown in FIG. 4 after it has been purified as its copper-containing form designated Cu-At2 in said Figures.
6. The process of producing a biologically active substance identified as bleomycin A5 in its copper-free form and as Cu- At5 in its copper-containing form which is one of the main components of bleomycin A and which gives a positive ninhydrin reaction, and gives positive Pauly, Ehrlich, Dragendorf and permanganate tests and negative Sakaguchi, Fehling, Tollens, ferric chloride and Mollisch tests, and exhibits the ultraviolet absorption spectrum shown in FIG. 3 and the infrared absorption spectrum shown in FIG. 4 after it has been purified as its copper-containing form designated Cu- At5 in said FIgures, said process comprising cultivating Streptomyces verticillus ATCC 15003 at a temperature of about 25* C. to 35* C. for at least two days under submerged aerobic conditions in an aqueous assimilable carbohydrate solution containing an assimilable nitrogenous nutrient until the substantial amount of the said antibiotic is produced and then recovering from the broth the bleomycin A5 thus produced by adsorption on a cation exchange resin and subsequent elution therefrom And then separating the bleomycin A5 from the other bleomycins present therewith by chromatography as the fraction which exhibits in its copper-containing form an Rf of about 0.51 in thin layer chromotography using silica gel and 10 percent ammonium acetate-methanol (1.1) and a negative Sakaguchi reaction.
7. A biologically active substance identified as bleomycin A5 in its copper-free form and as Cu- At5 4 l in its copper-containing form which is prepared by the process of claim 6 and which gives a positive ninhydrin reaction, and gives positive Pauly, Ehrlich, Dragendorf and permanganate tests and negative Sakaguchi, Fehling, Tollens, ferric chloride and Molisch tests, and exhibits the ultraviolet absorption spectrum shown in FIG. 3 and the infrared absorption spectrum shown in FIG. 4 after it has been purified as its copper-containing form designated Cu- At5 in said Figures.
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