The method of obtaining technical digoxin
(57) Abstract:The invention relates to pharmaceutical industry and relates to a method of obtaining technical digoxin. The method is carried out by fermentation followed by extraction with an aqueous solution of ethyl alcohol leaves of digitalis lanata, evaporation of the extract, extract of digoxin chloroform, evaporation of the chloroform extraction, chromatography was carried out on alumina, elution of the target product mixtures ethanol-chloroform, evaporation of the fractions containing digoxin, recrystallization technical digoxin from acetone and filtering. The invention relates to pharmaceutical industry, and in particular to methods of obtaining technical digoxin from the leaves of digitalis lanata. Digoxin is a cardiac glycoside and is one of the most well-known and well-proven pharmaceutical drugs cardiotonic action.Currently known a number of proprietary ways to get digoxin with implementation stage fermentation by moistening with water the leaves of digitalis lanata and curing them at an elevated temperature , ; MESI methylene chloride - ethanol (9: 1). A further selection of technical digoxin spend a countercurrent method in the system chloroform-benzene - methanol - water followed by purification on alumina  , extrapyramidal chloroform and purified by double passage through alumina using for the first chromatography was carried out of a mixture of chloroform - methanol (90:10), and the second mixtures of chloroform - methanol (95:5), chloroform - methanol (90:10), chloroform - methanol (50:50)  ; evaporation of the extract, followed by dissolving the dry residue in formamide, treatment with a mixture of methylene chloride - carbon tetrachloride, extraction of digoxin chloroform, add in one stripped off the water extract of acetone and purification of the resulting solution on the adsorbent Diaion HP - 20 with subsequent extraction of digoxin with a mixture of methylene chloride - methanol (97:3) ; evaporation, elution of the adsorbent Diaion HP-20 50% aqueous acetone extraction eluates chloroform . The recrystallization of the resulting product is carried out from ethanol , methanol, , , a mixture of chloroform - ethanol (1:1) , acetone , .However, the above methods have the following drawbacks. Among them is the use in the process of toxic solvents, solvents, possession the bot to improve the technology remains relevant.The most optimal method of obtaining digoxin described in the patent . In our proposed method of obtaining the fermentation of dry powdered feedstock is carried out in a similar way, but at the stage of extraction of the authors of the patent  used a toxic solvent is methanol, which replaced us on ethanol. Further purification of the authors of the patent  is performed using the chromatography was carried out one stripped off water VAT residue on the adsorbent Diaion HP - 20 using 50% aqueous acetone for elution, with subsequent extraction of the fractions containing digoxin, chloroform. We offer a cleaning method using more of the available sorbent - oxide of aluminium with the optimum particle size - 5/40, with digoxin was previously extrahieren from one stripped off water VAT residue with chloroform. Elution is performed with mixtures of chloroform - ethanol (39:1), chloroform - ethanol (38:2), chloroform - ethanol (37: 3) using flash chromatography. Previously proposed methods of receiving digoxin using as adsorbent alumina . However, in this practice exercise 2 chromatography was carried out, which increases the number of process steps and leads to a higher consumption of sorbent. The proposed method is ente  a chloroform-methanol mixture for elution by chloroform-ethanol. The resulting product was recrystallized from acetone, in a way similar to that described in the patent .The aim of the invention is a simplified method of obtaining digoxin by reducing the time and complexity of the process, improve efficiency, reduce consumption of solvents, as well as improving the technical and economic indicators. In addition, when selecting consumables accounted for their explosive properties, toxicity and availability.Example 1. 1 kg of crushed leaves of digitalis lanata content lanatoside With 0.10% and with the loss of moisture on drying 6% moisturize 2 l of purified water and maintained at a temperature of 451oC for 24 hours, then cooled to room temperature, add 2 l 96,4% aqueous ethanol and extracted for 3 hours with continuous stirring. Raw similarly extracted 2 more times, loading on each subsequent loading of 70% aqueous ethyl alcohol in a quantity equal merged the previous extract. The combined extract was evaporated to an aqueous VAT residue and extracted four times with chloroform, feeding on the first and second extraction 1/3 of the volume of water VAT residue, and the third and Thursday is up through the sorbent (0.3 kg of aluminum oxide with a particle size 5/40,), using the flash technique. For elution using chloroform and then a mixture of chloroform - 96,4% aqueous ethyl alcohol (39:1), mixture of chloroform - 96,4% aqueous ethanol (38:2), a mixture of chloroform - 96,4% aqueous ethanol (37:3). Fractions analyzed by thin-layer chromatography and containing digoxin, unite. The solvent is distilled under vacuum until a dry residue which is dissolved in 10 times the amount of acetone and left for crystallization at night. The precipitated crystals digoxin filtered and washed with acetone. Obtain 0.74 g of technical digoxin.Sources of information
1. PL 140548,1989.2. PL 143815, 1990.3. HU 183223, 1986.4. DD 160593, 1983.5. FR 2552767, 1985.6. HU 185302, 1987.7. HU 181889, 1985. The method of obtaining technical digoxin by fermentation in water crushed dried leaves of digitalis lanata (Digitalis lanata), extraction with aqueous alcohol, evaporation of the extract, extract of digoxin chloroform, evaporation of the chloroform extraction, chromatographic purification, crystallization from acetone and filtering, characterized in that the extraction is carried out in water ethyl alcohol in the ratio of raw materials-extractant 1: 4, chromatograph chloroform, and then a mixture of chloroform - 96,4% aqueous ethyl alcohol (39: 1), mixture of chloroform - 96,4% aqueous ethanol (38: 2), a mixture of chloroform - 96,4% aqueous ethanol (37: 3).
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a compound of general formula and its pharmaceutically acceptable salts and stereoisomers possessing anti-cancer activity, a based pharmaceutical composition, using them and a method of treating cancer with using them. In general formula I R1 and R2 are specified in hydrogen and halogen; R3, R5, R6, R7, R11, R12, R14 and R15 mean hydrogen; R4 means -OH; R8, R9 and R17 mean unsubstituted C1-C6 alkyl; R10 is specified in hydrogen, =O and ORb, wherein Rb means unsubstituted C1-C6 alkyl; R13 is specified in unsubstituted C1-C6 alkyl, OH-substituted C1-C6 alkyl and COH; R16 means -OH; and the line ----- represents either a bond, or an epoxy group.
EFFECT: producing pharmaceutically acceptable salts and stereoisomers possessing anti-cancer activity.
17 cl, 10 tbl, 5 ex