[Factors determining the stability of oleandomycin phosphate].

Comparative stability of crystalline and amorphous oleandomycin phosphate was studied. It was shown that the structure and humidity of oleandomycin phosphate were among the main factors determining its stability. Crystalline oleandomycin phosphate was highly stable and the effect of humidity on its stability was relatively low.

[Solubility of the polyene antibiotics nystatin and levorin in water-organic mixtures].

Solubility of the polyenic antibiotics levorin and nystatin in water-alcohol mixtures and in the water-acetone system was studied. Methanol, ethanol, n-propanol, isopropanol and n-butanol were used as alcohols. It was shown that the water-n-propanol system had the maximum dissolving properties with respect to levorin and nystatin.

[Novobiocin adsorption on active charcoal].

Adsorption of novobiocin from organic solutions with active carbons A and B was studied. It was found that the adsorption level depended on the nature of the organic solvent and markedly increased when active carbon A was replaced by active carbon B. Active carbon A was used for purification of the novobiocin acetone extracts from the admixtures.

[Solubility of the sodium salt of novobiocin in ethyl alcohol mixtures with other solvents].

Solubility of sodium novobiocin in binary mixtures of ethyl alcohol with ehtyl acetate, methylene chloride, diethyl ether, carbon tetrachloride or n-heptane was studied. Deviation in the sodium novobiocin solubility from the additivity was observed depending on the nature of the second component of the solvent mixture.

[Differential spectrophotometric method of analysing levorin in the culture broth and in the mycelium].

It was shown on model experiments that the microbiological method was not applicable for determination of levorin content in industrial intermediate products containing in addition levoristatin, since the presence of the latter made higher the results of the microbiological assay. Because of this till to the present date the quantitative content of levorin in the industrial intermediate products was determined photometrically using alcohol (pure solvent) as the reference solution. Still, this method also made higher the results of the assay, especially when the content of levorin was determined in the fermentation broth.

[Increase in the oleandomycin distribution coefficient at the extraction stage by using electron carrier-acceptors].

A possibility of increasing the distribution coefficient of oleandomycin on its extraction from the aqueous solution into the organic phase containing an electron carrier-acceptor was shown. It was found that the level of the oleandomycin equilibrium shift into the organic phase depended on the carrier nature, i. e.

[Separation of novobiocin, isnovobiocin and descarbamyl novobiocin by a thin-layer chromatographic method].

A thin-layer chromatographic method for separation of novobiocin, isonovobiocin and descarbamylnovobiocin using Silufol plates was developed. The method is simple and rapid. It provided clear separation of the components and using of diethyl ether, a simple individual separating solvent.

[Components of a native solution that displace the equilibrium distribution of oleandomycin during extraction].

A marked decrease in the coefficient of oleandomycin distribution in the system of the fermentation broth filtrate-butyl acetate was observed during the transfer from the 1st to the following extraction stages. It was supposed that the oleandomycin fermentation broth filtrate contained admixtures affecting significantly the antibiotic distribution between the aqueous phase and organic solvent.

[Streptoverticillium griseoviridum n. sp., a producer of the candidin-amphotericin B group, antifungal heptaene nonaromatic antibiotic 0185].

An actinomyceteous strain LIA-0185 producing a heptaenic non-aromatic antibiotic of the candidin type was isolated from a soil sample taken in the Georgian SSR under the programme of screening antifungal antibiotics. The taxonomic study of the strain showed that it belonged to the series of viridoflavum and had the following main taxonomic features: the sporophores in the whorls, straight, remote: the aerial mycelium from yellow to dark-olive-grey; the substrate mycelium olive; the soluble pigment absent; the melanine pigment was produced on the peptone medium; the culture formed H2S; assimilated glucose, mannose, inozide and to a lesser extent fructose; did not assimilate arabinose, xylose, sucrose, lactose, ramnose and raffinose. The strain inhibited the growth of yeast and fungi, grampositive bacteria and actinomycetes and produced a complex of non-aromatic heptaenic antibiotics.

[Use of aluminum salts for purifying oleandomycin culture broth].

It was shown that "nepheline coagulant"--Al2 (SO4)3-18H2O was effective in coagulating the admixtures in oleandomycin fermentation broth. The use of the "nepheline coagulant" in an amount of 1 to 3 per cent (by the weight) of the volume of the oleandomycin fermentation broth provided butyl acetate extraction of the antibiotic without formation of stable emulsion. Addition of the "nepheline coagulant" in an amount of 1 to 2 per cent (by the weight) to the fermentation broth markedly increased the rate of the fermentation broth filtration.

[Study of the equilibrium conditions for the extractive purification of oleandomycin].

Dependence of the oleandomycin distribution coefficient on the antibiotic concentration, duration of the filtrate storage, extraction temperature and salting-out agents was studied. The distribution coefficient of oleandomycin in the system of fermentation broth filtrate--butylacetate was much lower (about 3 times) than that in the system of oleandomycin phosphate aqueous solution--butylacetate. Addition of sodium sulfate to the aqueous phase provided a significant increase in the oleandomycin distribution coefficient.

[Ways to optimize the technological process of oleandomycin reextraction].

Dependence of the oleandomycin distribution coefficient on pH of the acqueous phase and temperature in the system of butylacetate extract-water acidified with orthophosphoric acid was studied. With a purpose of intensification of the process of oleandomycin reextraction, decreasing the antibiotic inactivation and evaporation of the organic solvent it was proposed to perfom oleandomycin extraction at pH 4.0--5.

[Nystatin and amphotericin B sorption complexes with polyvinyl-pyrrolidone in nonaqueous solvent systems].

Complexes of polyenic antibiotics with polyvinylpyrrolidone (PVP) can be used for preparing effective pharmaceutical forms soluble in water and consisting of fine dispersions. Studies were carried out; they are of great importance for revealing the mechanism of polyen interaction with neutral polymers, as well as for development of the technological processes for production of the pharmaceutical forms. The sorption isoterms of PVP with the molecular weight of 10 000 and 35 000 on nystatin and amphotericin B were obtained in the process of precipitation in the system of dimethylformamide-ethylacetate.

[Effect of gamma-irradiation on some biological and physico-chemical properties of polyene antibiotics].

Deep effect of gamma-rays on polyenic antibiotics was studied. It was shown that gamma-radiation induced radiation-chemical oxidation of the substances. The chromatographic analysis showed that the levorin degradation products were identical to the polyenic products of the antibiotic oxidative destruction.

[Study of the association of nystatin and amphotericin B in nonaqueous solvent systems].

Association of nystatin and amphotericin B in non-aqueous systems was studied with the method of equilibria dialysis. A specially treated celophane membrane arresting colloid associats and macromolecules with a molecular weight of more than 30000 in the systems of dimethylformamide-ethylacetate was used for the dialysis. Relation between the dialysis rate and the difference of the concentrations at every side of the membrane was used for estimation of the antibiotic colloid association level.

[Ionization of the acid-base groups of polyene antibiotics in aqueous solutions].

The acid-base characteristics of polyenic antibiotics, such as nystatin, mycoheptin and levorin in aqueous solutions were studied. A special procedure provided the use of potentiometric titration for investigation of ionization of the groups of vater-insoluble substances. The ionization constants of the carboxylic and amine groups of the antibiotics at several temperatures were determined.

[Actinomyces fulvoviolaceus ver. achromogenes var. nov., a producer of the new heptaene complex, fulvomycin].

An actinomycetous culture designated as LIA-0721 was isolated from a soil sample. It was close to Act. fulvoviolaceus by its morphologo-cultural features and differed from it in production of melanoid pigments and the spectrum of carbohydrate assimilation.

[Acid-base properties and the thermodynamics of amphotericin B ionization in aqeous solutions].

Acid-base properties of amphotericin B, polyenic antibiotic in aqueous solutions was studied. A special procedure provided the use of potentiometric titration for investigation of ionization of the groups of the water-insoluble substance. The ionization constants of the carboxylic and amine groups of the antibiotic were determined at several temperatures.

[Optical rotary dispersion of some heptaene antibiotics].

Experimental differences in the curves of the optic rotation dispersion (ORD) of cystrans-heptaenic antibiotics were found. The ORD curves of amphotericin B, mycoheptin, levorin components and isolevorin A2, components of criptomycin and candidin were registered. The curves of the ORD which were smooth had been prepared in dimethylsulphoxide in the spectral range at 450 to 600 nm.