METHOD OF PRODUCING BRANCHED OLIGOHEXAMETHYLENE GUANIDINE SALTS HAVING DEGREE OF PURITY SUFFICIENT FOR USE THEREOF AS PHARMACEUTICAL SUBSTANCE Russian patent published in 2020 - IPC C07C277/08 C07C279/02 C08G73/00 

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing branched oligohexamethylene guanidine (OHMG) salts, selected from hydrosuccinate, hydrochloride, hydrocitrate, hydrosalicylate, hydrosulphosalicylate having degree of purity sufficient for their use as a pharmaceutical substance. Method involves synthesis of technical hydrochloride MHF (OHMG-HC), presented by following general formula, where R is n₁, n₂ and n₃ are equal to 1–3, z is equal to 0.15–1.10, with number-average molecular weight M_n in the range from approximately 600 to 1100, polycondensation of hexamethylenediamine (HMDA) with hydrochloride guanidine (HCG) in molar ratio of 1.0:1.0 to 1.0:1.2 and minimum reaction temperature of 180 °C. Method is characterized by that polycondensation of HMDS with HMC to obtain technical OHMG-HC is carried out at temperature within 180–210 °C. Method further includes the following steps a)-e). Step a) is used to dissolve technical OHMG-HC in water to obtain 40–60 wt. % aqueous solution. At step b) addition of 1 volume part of aqueous solution of technical OHMG-HC to 4–6 volume parts of alcohol solution of alkali, selected from sodium hydroxide or potassium hydroxide and taken in amount of 1–4 equivalents per 1 equivalent of OHMG-HC, where alcohol is selected from ethanol, propanol or isopropanol, followed by stirring for 3–4 hours and holding for about 16 hours to separate phases. At step c), the phase containing most of the base of the OHMG is separated, and 1–3 equivalents of alkali are added thereto per 1 equivalent of OHMG-HC, followed by stirring for 3–4 hours and holding for approximately 16 hours before separation of phases. At step d), the phase containing the greater part of the base of the OHMG is separated, and adding portions of the acid selected from amber, hydrochloric, citric, salicylic or sulphosalicylic, until the precipitation of the corresponding inorganic salt ceases to obtain a solution of the technical salt of the OHMG selected from hydrosuccinate, hydrochloride, hydrocitrate, hydrosalicylate or hydrosulphosalicylate. At step e) separation of inorganic salt precipitate is carried out by filtration, evaporation of filtrate, dissolution of dry residue of technical salt of OHMG in 1 part of water, addition to obtained solution of 2 weight parts of alcohol selected from ethanol, propanol or isopropanol, and 1 part by weight of chloroform, stirring for approximately 1 hour, separating the lower phase containing purified branched-OHMGs salt, and evaporating it to obtain branched-chain solid salt.

EFFECT: disclosed method enables to obtain said salts of branched OHMG with purity sufficient for use thereof as a pharmaceutical substance.

1 cl, 9 tbl, 14 ex