EA041779B1 - APPLICATION OF ZINC(II) DIACETYLCYSTEINATE AS AN ANTIMICROBIAL AGENT - Google Patents

Description

The invention relates to a new biologically active chemical substance and can be used in veterinary medicine as a mucolytic drug for the treatment of animal diseases.

Known drug acetylcysteine, Acetylcysteinum (genus Acetylcysteini), chemical name Nacetyl-L-cysteine, showing mucolytic, expectorant and detoxifying properties. This drug is used for infectious diseases, accompanied by increased viscosity of sputum, and is also prescribed for otitis media, rhinitis and sinusitis. Molecular formula: (C5H9NO ₃ S), [1-2], the graphic formula is represented by formula 1:

H ₃ C

Formula 1. Graphic formula of Acetylcysteine

The disadvantage of this compound are allergic reactions: skin rash, itching, urticaria, bronchospasm (mainly in patients with bronchial hyperreactivity), drowsiness, fever; rarely tinnitus, reflex cough, local irritation of the respiratory tract, rhinorrhea (with inhalation use), burning at the injection site (with parenteral use).

Known drug carbocysteine, Carbocisteinum (genus Carbocisteini), chemical name 2-Amino3-(carboxymethylsulfanyl)propanoic acid, exhibiting mucolytic, expectorant and detoxifying properties. This drug is used in diseases of the respiratory system with profuse and viscous bronchial discharge, in preparing the patient for bronchoscopy or bronchography. Molecular formula (C5H9NO4S), [3-4], the graphical formula is represented by formula 2:

He

Formula 2. Graphic formula Carbocysteine

The disadvantage of this compound is contraindications for hypersensitivity, ulcerative lesions of the gastrointestinal tract, impaired renal function, acute glomerulonephritis, cystitis, pregnancy and lactation.

The aim of the invention is to find a new more effective means for the treatment of diseases of the respiratory system.

This goal is achieved by using a new coordination compound zincacs zinc diacetylcysteinate (II) [Zn(C5H ₈ NO ₃ S) ₂ ], the graphic formula of which is represented by formula 2:

Zn

Formula 2. Graphic formula of zinc diacetylcysteinate (P)

It is synthesized by the interaction of zinc sulfate with acetylcysteine (ACC) and has mucolytic activity. In the new compound, the mucolytic activity is enhanced by the combined action of the acetylcysteine residue and the metal ions of the complexing agent; solubility improves, the production of the drug is cheaper.

The chemical name of zinccas according to the IUPAC nomenclature of coordination compounds is zinc(II) diacetylcysteinate with the following general formula: [Zn(C5H ₈ NO ₃ S) ₂ ]. The general composition of the synthesized compound was established by oximetry, elemental analysis, and IR spectroscopy. The theoretical molecular weight of zinccas is 389, and experimentally found by cryoscopy is 390, the discrepancy is 0.3%, which is quite acceptable within the limits of experimental and theoretical calculation errors.

Example 1. To a suspension of 9.78 g (0.06 mol) of acetylcysteine in 40 ml of water is added 2.72 g (0.068 mol) of sodium hydroxide, stirred for 10 minutes until the acetylcysteine is completely dissolved and heated to 50°C. To a homogeneous solution is sprinkled with portions of 8.61 g (0.03 mol) of zinc sulfate: ZnSO ₄ -7H ₂ O, stirred, incubated for 40 min at a temperature of 50°C. The reaction mixture is cooled to 7-10°C, the precipitated crystals are filtered, washed with water from sulfates (quality control), alcohol and dried. 12 g (93.6%) of zinc diacetylcysteinate C ₁₀ H ₁₆ O ₆ N ₂ S ₂ Zn are obtained. Nitrogen content (%): found - 6.91; calculated - 7.02. Zinc dicetylcysteinate is a white crystalline substance, soluble in water, insoluble in alcohol.

Example 2. In order to assess the safety of the compound at an approximate therapeutic dose of 0.03 g/kg of body weight with water, orally in the form of a 10% solution was administered to white mice (weighing 18-20 g, number 5 pcs.) And chinchilla rabbits (weighing 2.5-2.7 kg, quantity 5 pieces) 2 times a day for 7

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Claims (4)

days. There were no animal deaths during the specified time. Acute toxicity was studied in experiments on white mice (weighing 18-20 g), from which 10 groups were formed according to the principle of paired analogues. Before the start of the study, laboratory animals, which were kept under normal conditions, were observed for 14 days. The last time food was given in the evening on the eve of the experiment, water intake was not limited. White mice zinccas in the form of a 10% solution was administered once orally in a volume of 0.5 ml. Control animals were injected with saline in appropriate volumes. Thus, according to the results of toxicological studies, it was determined that zinccas at a dose of 7.5 g/kg of body weight causes the death of all experimental animals (LD _1O o=7.5 g/kg). Chronic toxicity was studied in experiments on feeding the compound for 20 days on three groups of white mice (weighing 18-20 g) and three groups of chinchilla rabbits (weighing 2.5-2.7 kg) in 2-, 5- and 10- multiple approximate therapeutic dose (0.03 g/kg of body weight). Animals in the control groups did not receive the test compound. The laboratory animals were observed for 30 days. Example 3. The effect on the skin and mucous membranes was determined on rabbits (females, weighing 2.5-2.7 kg), which were daily applied to the skin with 2 drops of 5%, 1%, 0.5%, 0.1% - th solution of the compound for 21 days, their repeated local action was also studied. Animals of the control group were applied 2 drops of sunflower oil according to the same method. Animals were observed for 30 days. The effect of zinccas on the mucous membrane of the eye was studied on rabbits (females, weighing 2.5-2.7 kg, η = 5), which were divided into two groups. Animals of the first group in the conjunctival sac once instilled 0.1% solution of the compound in the amount of one drop, the second (control) - distilled water in the same amount. It has been established that the local irritating effect of zinccas on the mucous membranes of the eyes when administered for 14 days is not pronounced. A source of information 1. Kuzmin A.A. Anthelmintics in veterinary medicine. M.: AQUARIUM LTD. 2001-144 p. 2. Mashkovsky M. D. Medicines. In 2 vols. Vol. 1., Vol. 2. - M: Publishing House LLC Novaya Volna, 2004, p. 540 and 608. 3. Radjabov U., Ermamadova S.G., Rakhimova R.N., Mizhgoni Shukhratzoda. Synthesis and application of metal-containing bioactive coordination compounds. Dushanbe: Irfon, 2017, 151 p. 4. Veterinary preparations: reference book/Comp. L.I. Malanin [and others] ed. HELL. Tretyakov. Moscow: Agropromizdat, 1988, 319 p. CLAIM The use of di(X-acetyl E-cysteinate)zinc(II) represented by the formula as an antimicrobial agent. Eurasian Patent Organization, EAPO Russia, 109012, Moscow, Maly Cherkassky per., 2