Using tetranitrosyl complex of iron with thiophenol as anti-tumour medicinal agent

FIELD: chemistry.

SUBSTANCE: invention relates to use of a tetranitrosyl complex of iron with thiophenol of formula [Fe2(SC6H5)2(NO)4] as an anti-tumour medicinal agent in order to prepare a medicinal agent for treating oncological diseases. The invention also relates to a pharmaceutical composition and a set containing said complex.

EFFECT: invention ensures high efficiency of treatment.

8 cl, 1 tbl, 1 ex

 

The technical FIELD

The invention relates to tetranitroaniline binuclear complexes of iron and can be used in medical practice to create a medicinal product of a new generation for the treatment of cancer. Specifically, the present invention relates to the use of tetranitroaniline binuclear iron complex with thiophenols as anticancer drugs of new generation.

The LEVEL of TECHNOLOGY

In recent years, with the aim of creating drugs of new generation, used in the treatment of cancer, is an intensive search for anticancer agents based on transition metal complexes with improved spectrum of activity and reduced side effects in comparison with the already used clinical drugs, such as cisplatin, sodium nitroprusside, etc.

Interest in nitrosyl complexes of metals has increased due to open possibilities for their use as an effective NO-donors in medicine, in particular for the treatment of neoplastic diseases. The use of NO donors as a new class of antitumor agents is associated with the important role of NO in the process of growth of malignant tumors [Wink D., Vodovoz J., Cook, J., Biochemistry, 1998, 63, 7, pp.948-957]. It is shown that the nitric monoxide changes the level of apoptosis of Oholibah cells, the activity of a gene p53 and neoangiogenesis [Brune B., Scheneiderhan N., Nitric oxide evoked p53 accumulation and apoptosis, Toxicol Letters, 2003, 193, 2, PP. 19-23], and inhibits the activity of key repair protein O6-methyl-guanine-DNA-methyl-transferase mammals [L Liu, M. Xu-Welliver, S. Kanagula, H.E. Pegg, Inactivation and degradation of O6-alkylguanine-DNA alkyltransferase after reaction with nitric oxide., Canser. Res., 2002, 62, R-3043].

Binding of NO to the active centers of metallothionen, in particular, with megamovie iron-containing proteins, has been studied intensively [Ford P.C., Lorkovic I.M., Chem.Rev., 2002, 102, 993; Hoshino, M.; Laverman LE, Ford P.C., Coord. Chem. Rev., 1999, 187, R]. It is established that one of the forms of natural reservoirs are NO nitrosyl iron complexes with tolstushki ligands [A.R. Butler, Megson I.I., Chem. Rev.,2002, 102, pp.1155-1165].

Their synthetic models - ethers “red salt” Russa have the composition [Fe2(SR)2(NO)4], where R = Et, t-Bu, (CH2)4-CH3C6H5F, Ph [T. Thomas, J.H. Robertson, E.G. Cox, Acta. Crystalogr., 1958, 11, p.599; C. Glidewell, M.E. Harman, M.B. Hursthouse, I.L. Johnson, M. Motevalli, J. Chem.Res., 1998, 212, p.1676; R.E. Marsh, A.L. Spek, Acta. Crystalogr., Sect. B. Struct. Sci., 2001, 57, p.800; C. Jinhua, M. Shaoping, H. Jinling, L. Jiaxi, Chinese J. Struct. Chem., 1983, 2, p. 263; T.B. Rauchfuss, T.D. Weatherill,Inorg. Chem., 1982, 21, pp.827-830].

These binuclear diamagnetic serenadasunny complexes with R = Alk generate NO in thermo - or photoactivation [J.L. Bourassa, P.C. Ford, Coord. Chem. Rev., 2000, 200-202, pp.887-900] and can serve as a new promising anticancer NO-generousity AG is nami.

However, the known synthetic NO donors in different classes are used as therapeutic agents for the treatment of cancer, and is used only for reinforcement (in varying degrees, depending on the chemical nature of existing chemotherapeutic agents or radiotherapy [Wink D., Vodovoz J., Cook, J., Biochemistry, 1998, 63, 7, pp. 948-957; N.P. Konovalova, S.A. Goncharova, L.M. Volkova, T.A. Raevskaya, L. T. Eremenko, A.M. Korolev, Nitric Oxide: Biology and Chemistry, 2003, 8, pp.59-64; Yang, W., Rogers P.A., H. Ding, J. Biol. Chem., 2002, 277, pp. 12868-12873; O. Siri, A. Tabard, P. Pullumbi, R. Guilard, Inorg. Chim. Acta 2003, 350, p.633; J.L. Burgaud, E. Jngini, Del Soldato P. Ann, N.Y. Acad. Sci. 2002, 962, p.360; T. I. Karu, L. V. Pyatibrat, G. S. Kalendo, Toxicology Letters, 2001, 121, p.57].

In the work of A. Janczyk et al., Nitric Oxide, 2004, 10, 1, pp.42-50, studied the direct cytotoxic action of nitrosyl iron complex Na[Fe4S3(NO)7] on human melanoma cells in human and mouse. However, the nitrosyl complex of iron generates NO by photoactivation (even in darkness), and may not be used as anticancer drugs because of the high toxicity against normal cells.

Thus, there is a need for other antitumor tools with increased efficacy and reduced toxicity.

The present invention is to expand the Arsenal of anticancer agents and the creation of protivo the Holevo medicines on the basis of transition metal complexes with improved spectrum of activity and reduced side effects, in particular medicinal product on the basis of tetranitroaniline binuclear iron complex, acting as a donor of NO, with increased activity and reduced toxicity.

A BRIEF STATEMENT of the substance of the INVENTION

The authors of the present invention found that tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4] spontaneously emits NO decomposition in proton environments and has antitumor activity against tumor cells of mammals, in particular humans.

Thus, in one aspect the invention relates to the use of tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4] as anticancer drugs.

In another aspect the invention relates to the use of tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4] for anticancer drugs.

In the following aspect the present invention relates to pharmaceutical compositions containing an effective amount tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4] and the pharmaceutically preelimination.

In the following aspect the present invention provides a kit used for the treatment of cancer, comprising: (1) a pharmaceutical composition comprising tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4], in a sealed package; and (2) auxiliary tools.

DETAILED disclosure of the INVENTION

The present invention relates to the use of tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4] as anticancer drugs.

Tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4] known from the prior art. Getting tetranitroaniline complex of iron with thiophenols formula [Fe2(SC6H5)2(NO)4] from Fe2(I)2(NO)4and PhSH in the presence of Et3N described in article T.B. Rauchfuss, T.D. Weatherill,Inorg. Chem., 1982, 21, RR-830. Another way to get tetranitroaniline complex of iron with thiophenols formula [Fe2(SC6H5)2(NO)4] disclosed in the article by C. Glidewell, R.J. Lambert, M.E. Harman and M.B. Hursthouse, J. Chem. Soc., Dalton Trans., 1990, 10, RR-2690. The method consists in the interaction of Na[Fe4S3(NO)7] tetrafluoroborate phenyldiazonium PhN2 +BF4-in a solution of acetonitrile at 0°C.

But none of the documents of the prior art does not disclose biologically active properties, any purpose or use tetranitroaniline complex of iron with thiophenols in any field.

Tetranitroaniline complex of iron with thiophenols formula [Fe2(SC6H5)2(NO)4] can be obtained by known methods of synthesis, for example, by the method disclosed in the article by C. Glidewell, R.J. Lambert, M.E. Harman and M. B. Hursthouse, J. Chem. Soc., Dalton Trans., 1990, 10, RR-2690, for similar tetranitroaniline complexes [Fe2(SR)2(NO)4], where R is an alkyl(C1-C8), CH2CO2IU, CH2CH2HE or 2-pyrimidinyl. The method consists in the interaction of bis(μ-thiosulfate-S)-bis-(dinitrodiphenyl)(2-) sodium: Na2[Fe2(S2O3)2(NO)4] in aqueous solution with thiols RSH in the presence of sodium thiosulfate, Na2S2O3·5H2O and NaOH.

The inventors have obtained the complex [Fe2(SC6H5)2(NO)4] interaction tetranitroaniline thiosulfate binuclear iron complex with thiophenols in their stoichiometric ratio in an aqueous alkaline medium, followed by separation of the target product by extraction with dichloromethane and Chris is alsacia of dichloromethane.

The inventors have found that tetranitroaniline complex of iron with thiophenols [Fe2(SC6H5)2(NO)4] is an effective donor NO highlighting NO spontaneous decomposition in proton environments (such as water, blood and its components, physiological solutions, and the like), and do not require thermal or photoactivation, as for other known nitrosyl iron complexes. This has a significant advantage in the treatment of neoplastic diseases: for activation of the complex [Fe2(SC6H5)2(NO)4] does not need to be heated or irradiated (as, for example, in photodynamic therapy). The authors of the present invention has also shown that tetranitroaniline binuclear iron complex with thiophenols inhibits the growth of tumor cells in mammals, in particular humans.

Thus, in the first aspect of the present invention relates to the use of tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4] as anticancer drugs.

In particular, tetranitroaniline binuclear iron complex with thiophenols can be used for the treatment of myeloid leukemia.

Tetranitroaniline binuclear iron complex with thiophenols according to the present invention suitable for Engibarov the Oia growth of tumors in mammals, and it is preferably introduced in the form of pharmaceutical compositions comprising an effective antitumor amount of a compound according to the present invention in combination with at least one pharmaceutically or pharmacologically acceptable carrier. The media is also known from the prior art, as excipient, filler, excipient, additive or diluent, is any substance which is pharmaceutically inert, gives the appropriate consistency or form to the composition, and does not reduce therapeutic efficacy of antitumor compounds. The media is a "pharmaceutically or pharmacologically acceptable"if it does not cause any adverse, allergic or other adverse reactions when administered to a mammal or human, respectively.

In another aspect the invention relates to the use of tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4] for the manufacture of anticancer drugs.

The present invention also provides pharmaceutical compositions containing an effective amount tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4] and a pharmaceutically acceptable carrier.

Preferably as a pharmaceutically acceptable but is of Italia use protonotariou Wednesday, more preferably, the mixture protonotaria environment and dimethyl sulfoxide.

In the present invention as protonotaria environment preferably use water, saline solution, water-soluble biopolymers.

Preferably, tetranitroaniline complex of iron with thiophenols is present in the pharmaceutical composition in the amount of 50-100 microns.

Pharmaceutical compositions containing the anti-tumor compound according to the present invention can be obtained by any conventional method. Necessary preparative form chosen depending on the selected method of administration. Compositions according to the invention can be prepared for any way of introduction so that the target tissue was available in this route of administration. Suitable routes of administration include, but are not limited to, oral, parenteral (e.g. intravenous, intraarterial, subcutaneous, rectal, intramuscular, intraorbital, intracapsular, intraspinal, intraperitoneal or intrasternally), local (nasal, percutaneous, ocular), vnutrishkolnoe, vnutriobolochechnoe, small intestine, lung, intralymphatically, intracavitary, vaginal, transurethrally, intradermal, ear, intramammary, transbukkalno, orthotopic, intratracheal, inside jehovae, percutaneous, endoscopic, cressilia, sublingual and intestinal introduction.

Pharmaceutically acceptable carriers for use in the compositions according to the present invention are well known to the specialist, and they are chosen depending on a number of factors: specific antitumor compound and its concentration, stability and expected bioavailability; the disease, disorder or condition of the person being treated with the composition; the subject, its age, weight and General condition; and the route of administration. Suitable carriers can be easily determined by the expert (J.G. Nairn in: Remington''s Pharmaceutical Science (edit. A. Gennaro), Mack Publishing Co., Easton, Pa, (1985), pp.1492-1517).

The compositions preferably are in the form of tablets, dispergiruyushchie powders, pills, capsules, gelatin capsules, dripping with the floor, gels, granules, solutions, suspensions, emulsions, syrups, elixirs, tablets, pills, cakes or any other dosage forms that can be administered orally. Technology and composition to obtain a suitable in accordance with the present invention the oral dosage forms described in the literature (Modern Pharmaceutics, chapters 9 and 10 (ed. Banker and Rhodes, 1979); Lieberman and others, the Pharmaceutical Dosage Form: Tablets (1981); and Ansel, Introduction to Pharmaceutical Dosage Forms, second edition (1976)).

Compositions according to the present invention for oral administration include eff is active antitumor amount of a compound according to the invention and a pharmaceutically acceptable carrier. Suitable carriers for solid dosage forms include sugars, starches, and other common substances, including lactose, talc, sucrose, gelatin, carboxymethylcellulose, agar, mannitol, sorbitol, calcium phosphate, calcium carbonate, sodium carbonate, kaolin, alginic acid, gum Arabic, corn starch, potato starch, sodium saccharinate, magnesium carbonate, tragakant, microcrystalline cellulose, colloidal silicon dioxide, nitrocresols, talc, magnesium stearate and stearic acid. Further, such solid dosage forms may be uncoated or can be coated with a known coating methods, for example, to delay disintegration and absorption.

Antitumor compound according to the present invention is also preferably used for the preparation of dosage forms for parenteral administration, for example, in the form of dosage forms for injection intravenous, intraarterial, subcutaneous, rectal, intramuscular, intraorbital, intracapsular, intraspinal, intraperitoneal or intrasternally ways. Compositions according to the invention for parenteral administration include an effective antitumor amount of antitumor compounds in a pharmaceutically acceptable carrier. Suitable for parenteral administration dosiro the data forms include solutions, suspensions, dispersions, emulsions, or any other dosage form, which may be introduced parenterally. Methods and compositions for receiving parenteral dosage forms are known from the prior art.

In the composition according to the invention may be included for various purposes a small number of additional components that are well known in the pharmaceutical industry. These components are for the most part give properties that increase the retention time of antitumor compounds in the introduction, we contribute to the stability of the composition, regulate pH value, facilitate the introduction of antitumor compounds in pharmaceutical compositions, etc. Each of these components individually is present in amounts of, preferably, less than about 15 wt.%, more preferably, less than about 5 wt.% and, most preferably, less than about 0.5 wt.% calculated on the total weight of the composition. Some components, such as fillers or diluents, can be up to 90 wt.% calculated on the total weight of the composition, as is well known in the technology of preparation of medicines. Such additives include createsite components to prevent the deposition of iron complex with thiophenols, surfactants, wetting and and emulsifying agents (for example, lecithin, Polysorbate-80, tween®80, pluronic-60, polyoxyethylenated), preservatives (e.g., ethyl-p-hydroxybenzoate), protects from the effects of microbes means (for example, benzyl alcohol, phenol, m-cresol, chlorobutanol, sorbic acid, thimerosal, and paraben), agents for adjusting the pH or buferiruemoi agents (e.g., acids, bases, acetic sodium, sorbitan-monolaurate), components for control osmolarity (for example, glycerin), thickeners (for example, aluminum monostearate, stearic acid, cetyl alcohol, stearyl alcohol, guar gum, methylcellulose, hydroxypropylcellulose, tristearin, complex citylove esters wax, polyethylene glycol), pigments, dyes, additives, giving fluidity, non-volatile silicones (for example, cyclomethicone), clay (e.g. bentonite), adhesives, increasing the volume of agents, flavorings, sweeteners, adsorbents, fillers (for example, water, saline, solutions of electrolytes), binders (for example, starches such as corn starch, wheat starch, rice starch or potato starch, gelatin, tragakant, methylcellulose, hypromellose, sodium carboxymethyl cellulose, polyvinylpyrrolidone, sugars, polymers, gum Arabic), loosening agents (e.g., starches such as corn is rahmel, wheat starch, rice starch, potato starch or carboximetilkrahmal, structured polyvinylpyrrolidone, agar, alginic acid or its salt, such as sodium alginate, nitrocresols or crosspovidone), lubricating agents (for example, silicon dioxide, talc, stearic acid or its salts, such as magnesium stearate, or polyethylene glycol), agents for coatings (for example, concentrated solutions of sugar, including gum Arabic, talc, polyvinylpyrrolidone, carbopol, polyethylene glycol, or titanium dioxide) and antioxidants (e.g., sodium metabisulfite, sodium bisulfite, sodium sulfite, dextrose, phenol and thiophenol).

According to a preferred variant implementation of the pharmaceutical composition according to the invention includes at least one non-aqueous pharmaceutically acceptable solvent and antitumor compounds having a solubility therein at least about 10-60 mg/ml Without regard to any particular theory believe that the solubility in dimethyl sulfoxide antitumor compounds can be directly related to its effectiveness. Also preferred is that the antitumor compound has an ID value100(i.e., the drug concentration causing 100%inhibition of the images is of the colony), at least 4 times less than that of cisplatin, when carrying out measurements in accordance with the methodology described in the book "Experimental evaluation of anticancer drugs in the USSR and the USA" Ed. by Z.P. Sofianou, A.B. sarcina (USSR), A. Goldin, A. Klein (USA) M.: Medicine, 1979, p.71-105.

The introduction of the dosage forms listed ways can be continuous or intermittent, depending, for example, on the physiological state of the patient, whether the purpose of the introduction of therapeutic or prophylactic, and other factors, known or estimated practitioner.

Dose and scheme to introduce the pharmaceutical compositions according to the invention can be easily determined by the oncologist. It is clear that the dose of anticancer compounds depends on age, sex, health and weight of the recipient, type the concurrent treatment, if any, frequency of treatment and the nature of the desired effect. For any way of introduction, the exact amount used anticancer compounds, as well as appointed by the dose required to achieve the described here useful effects, also depends, in part, on factors such as bioavailability of anticancer compounds, a human disease that is treated, the desired therapeutic dose, and other factors that obvious expert is.

The concentration of antitumor compounds of the present invention in the liquid pharmaceutical composition is most preferably 50-100 μm. Generally, the preferred relatively low concentration, so as anticancer compound is most soluble at low concentrations.

Emulsion for parenteral administration can be prepared by dissolving an antitumor compound in any pharmaceutically acceptable solvent capable of dissolving the compound (e.g., DMSO, dichloromethane), with formation of a solution. To the solution was added with stirring with an appropriate volume of media, which is an emulsion, such as emulsion (Liposyn II or Liposyn III, getting a pharmaceutically acceptable emulsions for parenteral administration to a patient. If desirable, such emulsions can be prepared with the content of the minimum number, or without, a solution of Cremophor®.

Solutions for parenterale injection can be prepared by dissolving an antitumor compound in any pharmaceutically acceptable solvent capable of dissolving the compound (e.g., DMSO), with formation of a solution. To the solution was added with stirring with an appropriate volume of media that represents protonotariou environment (salt solutions,solutions of sugars, water-soluble polymers, proteins, electrolytes) for parenteral administration to a patient.

So, for example, preparative liquid forms as a carrier typically use non-aqueous pharmaceutically acceptable polar solvents, such as oils, alcohols, amides, esters, ethers, ketones, hydrocarbons and mixtures thereof, and water, salt solutions, solutions of dextrose (for example, DW5), solutions of electrolytes or any other proton, pharmaceutically acceptable environment.

Suitable non-aqueous pharmaceutically acceptable polar solvents include, but are not limited to, amides (for example, dimethylacetamide (DMA), diethylenetriaminepenta, dimethylformamide, N- (β-hydroxyethyl) lactamide, N,N-dimethylacetamide, 2-pyrrolidinone, 1-methyl-2-pyrrolidinone or polyvinylpyrrolidone); esters (for example, 1-methyl-2-pyrrolidinone, 2-pyrrolidinone, the acetic acid esters, such as monoacetin, diacetin and triacetin; aliphatic or aromatic esters, such as ethylcaproic or ethyloctanoic, alkyllead, the benzyl benzoate, benzoylacetate, dimethylsulfoxide (DMSO), esters of glycerol, such as mono-, di - or triglyceriderich or tartratami, ethylbenzoic, ethyl acetate, ethylcarbonate, ethyllactate, etiloleat, esters of fatty acids sorbitan, esters of fatty acids and of polyethylene glycol (PEG), glicerio stearate, esters of glycerides such as mono-, di - or triglycerides, fatty acid esters, such as isopropylmyristate, esters based on fatty acids and PEG, such as PEG-hydroxyoleic and PEG-hydroxystearate, N-methylpyrrolidinone, pluronic-60, polyoxyethylenated polyesters based on sorbitol and oleic acid, such as poly(oksietilenom)30-60orbitale(oleate)2-4, poly(oksietilenom)15-20monooleate, poly (oksietilenom)15-20mono-12-hydroxystearate and poly(oksietilenom)15-20monoricinoleate; polyoxyethylenesorbitan esters such as polyoxyethylene sorbitan monooleate, polyoxyethylenesorbitan, polyoxyethylenesorbitan, polyoxyethylenesorbitan and Polysorbate®20, 40, 60 or 80 company ICI Americas, Wilmington, DE; polyvinylpyrrolidone; modified acceleratedly esters of fatty acids, such as gidrirovannoe polyoxyl(40)-castor oil and polyoxyethylene castor oil (for example, a solution of Cremophor®EL or Cremophor solution®RH 40); esters of fatty acid and saccharide (i.e., the condensation product of a monosaccharide (e.g., pentoses such as ribose, ribulose, arabinose, xylose, lyxose, xylulose; hexose, such as glucose, fructose, galactose, mannose and sorbose; triose, tetrose, heptose and actoz), disaccharides (e.g. sucrose, maltose,lactose and trehalose) or oligosaccharide, or a mixture thereof with a fatty acid (fatty acids) with 4 to 22 carbon atoms (for example, saturated fatty acids such as Caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid and stearic acid, and saturated fatty acids, such as palmitoleic acid, oleic acid, elaidic acid, erucic acid and linoleic acid)), or steroid esters); alkalemia, aryl, or cyclic ethers with 2-30 carbon atoms (for example, diethyl ether, tetrahydrofuran, dimethyldithiocarba, monotropy ether of diethylene glycol); glycoluril (simple ester of polyethylene glycol and tetrahydrofurfuryl alcohol); ketones with 3 to 30 carbon atoms (for example, acetone, methyl ethyl ketone, methyl isobutyl ketone); aliphatic, cycloaliphatic or aromatic hydrocarbons having 4-30 carbon atoms (for example, benzene, cyclohexane, dichloromethane, dioxolanes, hexane, n-decane, n-dodecane, n-hexane, sulfolan, tetramethylarsonium, tetramethylsilane, toluene, dimethylsulfoxide (DMSO) or tetramethylsilane); alkyl or aryl halides containing 1-30 carbon atoms and optionally more than one halogen atom as a substituent; dichloromethane; monoethanolamine; petroleum ether; trolamine; omega-3-polyunsaturated fatty acids (for example, alpha-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid or docosa Aksenova acid); polyglycidyl ester 12-hydroxystearate acid and polyethylene glycol (Solutol® HS-15 BASF, Ludwigshafen, germany); polyoxyethyleneglycol; sodium laurate; sodium oleate; or servicemanual.

Preferably as a pharmaceutically acceptable carrier in the present invention to use protostegana environment, such as water, saline solutions, water-soluble polymers, proteins, solutions of dextrose (for example, DW5), electrolyte solutions or alcohols from the catalogue “PAA Laboratory's”, R.26, 2006.

Compositions, for example, represent a 0.2% solution of DMSO in culture medium RPMI 1640 with dissolved in it tetranitroaniline binuclear complex of iron with thiophenols with a concentration of 50-100 μm. Pharmaceutically acceptable carrier medium RPMI 1640 - may be replaced by a saline solution, starch and other media selected by a specialist, depending on the method of administration, type of tumor and the subject being treated.

The following aspect of the present invention features a kit for the treatment of cancer, which includes: (1) a pharmaceutical composition comprising tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4], in a sealed package; and (2) auxiliary tools.

The set may win a composition in the form of a single dosage form or in multiple doses. The set can include forms for oral or parenteral administration.

Pharmaceutical composition in the kit can be placed in glass or plastic vials, ampoules, bottles, measured cartridges for injectors, blisters, capsules, sachets with the composition used, respectively, for oral or parenteral form.

Auxiliary means include fluid recovery composition introduced parenterally, if she's in the set is presented in a concentrated form, for example, in the form of solids, dried drug etc.; means for receiving oral liquid forms and forms for injectionex tempore. As a liquid for recovery can be used water for injection, saline solution, lidocaine and the like To restore the composition applied in liquid form by mouth, can be used glucose, sugars, syrups, etc.

Optional auxiliary tool set includes tools for dissection of youporon, means for sealing the opened reusable youporon, liners statement.

Pharmaceutical composition, which represents a solid dosage form for oral administration may be presented as a set in the form of tablets, capsules in blisters, vials, bottles, vials, bags and so on The pharmaceutical composition constituting the liquid dosage form for parenteral or oral administration may be presented as a set in vials, capsules, ampoules, cartridges, etc.

Example set for parenteral administration includes packaging, which includes instructions for use, ampoules or vials with dry composition, and vials with saline solution for injection. In the packaging goes a device for opening ampoules. The ampoules are Packed in blisters of 10 vials.

Other options set obvious to the person skilled in the art from the above description.

Examples

The following examples are given only as an additional illustration of the invention and they should not be construed as limitations of the invention.

Example of getting tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4]

The synthesis was carried out in an inert atmosphere. Distilled water for 30 minutes, saturated with argon. In the flask Slanka put 0,508 g (3.2 mmol) of Na2S2O3·5H2O (Aldrich), 0,588 g (1.0 mmol) of Na2[Fe2(S2O3)2(NO)4]·4H2O synthesized according to the method [N.A. Sanin, S.M. Aldoshin, TN. Rudnev, N. Golovin, Shilov G.V., Y.M. who Olga, V.M. Martynenko, NS Hovhannisyan, "Synthesis, structure and solid-phase transformations of nitrosyl iron complex Na2[Fe2(S2O3)2(NO)4]·4H2O", Coordination Chemistry, 2005, 31, 301-306], 0.2 g (5.1 mmol) granulated NaOH (Aldrich) and 0.52 ml (5.1 mmol) of C6P5SH (Aldrich). To the mixture was added 40 ml of H2O and intensively stirred for 2 hours at room temperature. At the end of this procedure, carried out the extraction of the product with dichloromethane (Aldrich) in the air three times in 15 ml. of All fractions were combined and the resulting red solution was evaporated to 1/5 of the initial volume, filtered through a porous glass filter N4 and left in air for several hours. Formed after removal of the solvent a dark blue crystals were air-dried. The product yield was 0,319 g (87%).

The structure of the obtained iron complex was investigated by the following methods.

Elemental analysis for Fe2S2C12H10N4O4. Found, %: Fe 24,82; S 14,20; N 12,38; C 32,03; H 2,20. Calculated, %: Fe 24,89; S 14,22; N To 12.44; C 32,01; H 2,22; O 14,22.

The IR spectrum of the sample were recorded on a spectrometer Fourier SPECTRUM BX-II. The sample was prepared in the form of tablets with KBr (1 mg analyte in 300 mg KBr).

IR spectrum (cm-1): 1778,1763, 1723, 1583, 1478, 1441, 1303, 1181, 1118, 1092, 1071, 1024, 999, 916, 834, 734, 694, 688.

Mössbauer absorption spectra were shot on set is VCE WissEl, operating in constant acceleration. Source served as the Co57in the matrix Rh. Measurements of the spectra at low temperatures was performed using flow helium cryostat CF-506 (Oxford Instruments) with controlled temperature. Processing mössbauer spectra was performed using the least squares method assuming Lorentzian form of individual spectral components.

Parameters NGR spectroscopy:

The isomer shift - 0,074 mm·with-1;

Quadrupole expansion - 0,971 mm·with-1.

The study of the cytotoxicity of nitrosyl iron complex on tumor human cellsin vitro

For the study used the following line human tumor cells: carcinoma ovarian SKOV3, myeloid leukemia K, carcinoma of the breast MCF7, non-small cell lung cancer A. Cells were grown in monolayer in RPMI medium 1640 containing 10% fetal calf serum, at 37°C and 5% CO2. For experiments cells were planted in 96-well plates and were grown in the same conditions.

Before the experiment, the compound was dissolved in 200 μl of DMSO, and then brought to the desired concentration of the nutrient medium RPMI 1640. The final concentration of DMSO in the sample did not exceed 0.2% and had no effect on cell growth.

Testing the cytotoxic effect was performed using the MTT-test, based on what sposobnosti dehydrogenases of living cells to restore unpainted salt tetrazole in blue crystals formazan, soluble in dimethyl sulfoxide (DMSO). The connection was made in the wells in a volume of 20 μl in 4 final concentrations (µm) 100, 50, 25 and 10. The total volume of incubation was 200 ál. Cells with the drug were incubated in the above conditions within 72 hours. After incubation, the cells were added MTT reagent and incubated under the same conditions for 2 hours. Then the resulting crystals formazan was dissolved in 100 μl DMSO at 37°C for 20 minutes. The optical absorption of DMSO solutions were measured on an optical counter to advance the plate at a wavelength of 540 nm. The results were expressed as average values for 4 parallel measurements as inhibition of cell growth in %: (1 - experience/control)×100. A connection is considered active if the concentration of 100 μm on one of the 3 cell lines caused a growth inhibition of 50% or more (IR50≤ 100 µm). The measurement error did not exceed 5%.

As Comparators in the study used well-known clinic anticancer drug cisplatin (cis-DDP) and carmustine (mechlorethamine).

Nitrosyl complex of iron with thiophenols showed cytotoxic activity on all cell lines (table 1). The complex was most active in cells of the myeloid leukemia K (IR50= 20 μm), an activity comparable to the activity of the platinum complex cis-DDP (the K 50= 20 μm). The most resistant to the action of the studied complex was the cell line of lung cancer A and carcinoma of the ovary SCOV3.

The complex [Fe2(SC6H5)2(NO)4] has a cytotoxic effect on tumor cells of various origins: myeloid leukemia K, carcinoma of the breast MCF7, non-small cell lung cancer A549 and carcinoma ovarian SKOV3. The toxicity of the claimed anti-cancer drugs is much lower (LD100= 60 mg/kg)than cisplatin (LD100= 16 mg/kg).

Table 1
Cytotoxic activity of nitrosyl iron complex with thiophene [Fe2(SC6H5)2(NO)4] on the lines of human tumor cells
№ p/pMedicationCell line, IR50, mcm
CMCF7A
1[Fe2(SC6H5)2(NO)4]2065100
2cis-DDP17 5037
3Carmustin20058570

In accordance with the methodological guidelines for the study of antitumor activity of pharmacological substances studies on transplantable tumors of mice Ca-755 and melanoma B-16 (in mice-the first generation hybrids BDF1(C57Bl/6 × DBA/2) and DBA/2weighing 18-25 g, obtained from the Department of laboratory animals of the Russian them. N.N. Blokhin Russian Academy of medical Sciences). Revealed moderate statistically significant compared with control anti-tumor effect of the proposed drug in doses of 10-75 mg/kg by daily intraperitoneal injection for 5 days.

1. Application tetranitroaniline complex of iron with thiophenols formula [Fe2(SC6H5)2(NR)4] as anticancer drugs.

2. Application tetranitroaniline complex of iron with thiophenols formula [Fe2(SC6H5)2(NO)4] to obtain drugs for cancer treatment.

3. Pharmaceutical composition comprising an effective amount tetranitroaniline complex of iron with thiophenols formula [Fe2(SC6H5)2(NO)4

4. The pharmaceutical composition according to claim 3, where the pharmaceutically acceptable carrier used protonotariou environment.

5. The pharmaceutical composition according to claim 3, where the pharmaceutically acceptable carrier, a mixture of protonotaria environment and dimethyl sulfoxide.

6. The pharmaceutical composition according to any one of claims 4 or 5, where as protonotaria environment using water, saline solution, water-soluble biopolymers.

7. The pharmaceutical composition according to claim 3, where tetranitroaniline complex of iron with thiophenols is present in the amount of 50-100 microns.

8. The set used for the treatment of cancer, comprising: (1) a pharmaceutical composition comprising tetranitroaniline binuclear iron complex with thiophenols formula [Fe2(SC6H5)2(NO)4], in a sealed package; and (2) auxiliary funds.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to complex compound of iron with carbohydrate. Complex compound, in addition to iron (III) contains iron (II). Per cent of iron (II) in terms of total amount of iron in complex compound constitutes, at least, 2 wt %. Carbohydrate is selected from group, consisting of natural carbohydrates or synthetic derivatives of carbohydrates, such as starch, hydrolysed starches, dextrins, in particular such as maltodextrin, maltose syrup, glucose syrup, cyclodextins, dextrans, saccharides. Per cent of carbohydrate in terms of complex compound of iron with carbohydrate constitutes from 10 to 80 wt %. Method of obtaining complex compound of iron with carbohydrate includes the following stages. Water solution of suspension of carbohydrate is prepared. After that, iron (III) salts are added at constant pH value within the range from 7 to 13. Iron (III) salt is selected from group, consisting of iron (III) chloride and iron (III) sulfate. Water solution or suspension is heated with further cooling. Formed complex compound of iron with carbohydrate if isolated. Precipitation of complex compound of iron with carbohydrate is performed by addition of one or more alcohols, such as ethanol or propanol. Obtained complex compound is used for production of medication for treatment of iron-deficient anemias, which is well absorbed in organism in case of peroral intake.

EFFECT: iron, included into composition of medication is better resorbed and better tolerated by organism than pure iron preparations.

26 cl, 1 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing trihydrate of iron (II) aminobutyrate-riboflavinate Fe(C4H8O2N)(C17H19O6N4) 3H2O, which can be used as a biologically active additive which enhances growth and development of animals. The method is implemented by mixing an aqueous suspension of riboflavinate and iron (II) gamma-aminobutyrate in equimolar ratio and temperature 70-80°C.

EFFECT: high output while cutting the time for implementing the method.

1 cl, 3 ex

FIELD: agriculture.

SUBSTANCE: invention relates to a novel compound - dihydrate of iron (II) hydroascorbate riboflavinate

(II) Fe(C6H7O6)(C17H19O6N4)2H2O which is used as an additive.

EFFECT: improved development and growth of chickens.

1 cl, 1 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to 1-alkenylimidazole derivatives of general formula 1 , where R is vinyl, allenyl or isopropenyl, R1 is hydrogen or methyl, E is Zn (II) or Fe(III), An is chlorine or acetate, n equals 1, 2 or 4, except compounds where R is vinyl, R1 is hydrogen, E is Zn(II), An is chlorine or acetate and n equals 2.

EFFECT: compounds have antihypoxic properties for different types of hypoxia.

5 ex, 8 tbl

FIELD: process engineering.

SUBSTANCE: invention relates to complete methane oxidation catalysts and can be used in industries using diesel fuel. Invention covers complete methane oxidation catalysts based on strontium hexaferrites of the following composition: SrMnxFe12-xO19, where x=0, 1, 2, 6. Proposed method comprises settling catalyst components with the help of NH4HCO3 solution at constant pH equal to (7.1 to 8.0) and temperature not lower than 70°C with subsequent stages of filtration, rinsing, drying and roasting. Proposed method comprises also the stage of heat treatment at 800° to 1000° C and is realised in the presence of above described catalysts.

EFFECT: high degree of methane conversion at relatively low temperatures.

6 cl, 2 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a polyolefin synthesis method and more specifically to a polyethylene synthesis method. Polyethylene is a copolymer of ethylene with 1-alkenes. The invention also relates to polyethylene synthesis catalyst systems. The catalyst system is a mixture of metallocenes: hafnocene and an iron-based complex, an activating compound and a support. The invention also relates to films made from polyethylene and packets made from the said films.

EFFECT: disclosed catalyst system enables production of polyethylene with given molecular weight distribution in a single reactor.

16 cl, 3 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing iron (II) oxalate by directly reacting metal with acid in the presence of atmospheric oxygen and a liquid phase while stirring. The process is carried out in a bead mill. The liquid phase solvent used is water with mass ratio of the liquid phase to glass beads equal to 1:1, content of oxalic acid in the initial load is between 0.5 and 2.0 mol/kg, and content of stimulating sodium chloride additive is between 0.02 and 0.10 mol/kg. Crushed grey cast iron which is stirred by a blade mixer is taken in amount of 30% of the mass of the rest of the load. The process is started and carried out at temperature in the interval from (50±2) to (93±2)°C while bubbling air under conditions for stabilising temperature using a heated liquid bath and controlling using a sample taking method and determination of content of iron (II) and (III) salts in the samples, and residual quantity of acid up to virtually complete conversion of the latter into salt. After that air bubbling, external heat supply for stabilising temperature and stirring are stopped. The suspension of the reaction mixture is separated from the glass beads and particles of unreacted metal alloy and filtered. The filtration residue is washed with distilled water and taken for further purification through recrystallisation, while the filtrate and the washing water are returned to the load for the repeated process. Iron (II) oxalate, which is separated from the reaction mixture by traditional filtering, is virtually the only product of conversion.

EFFECT: liquid phase used together with the sodium chloride additive can be repeatedly returned to the process.

10 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: iron (II) fumarate can be used in different fields of chemical practice, in analytical control and in scientific research, through direct reaction of iron with fumaric acid in the presence of a catalyst, where the catalyst used is molecular iodine in amount of 0.025 to 0.1 mol/kg of the initial load, iron is taken in large excess in form of shells on the entire height of the reactor, false bottom and blade mixer, as well as in form of crushed cast iron and(or) reduced iron powder, the liquid phase solvent used is butylacetate, in which iodine and fumaric acid are at least partially dissolved, where fumaric acid is taken in amount of 0.8 to 1.2 mol/kg of the initial load, loading is done in the sequence: glass beads, liquid phase solvent, fumaric acid, iodine, and then crushed cast iron and(or) reduced iron powder; the process is started at room temperature and is carried out in a vertical type bead mill with ratio of mass of beads to mass of crushed cast iron and(or) reduced iron powder equal to 4:1, at temperature ranging from 18 to 45°C while bubbling air with flow rate of 0.95 l/min-kg of the liquid phase and using forced cooling and controlling using a sampling method until complete exhaustion of the loaded acid for formation of salt, after which stirring and cooling are stopped, the reaction mixture is separated from glass beads and unreacted crushed cast iron and(or) reduced iron powder and filtered, the residue is washed with butylacetate and taken for recrystallisation, and the filtrate and washing butylacetate are returned to the repeated process. Amount of acid used in extracting the product (without loss during purification) ranges from 89 to 96.5%, which depends on conditions for carrying out the process.

EFFECT: improved method of producing said product.

8 ex

FIELD: chemistry.

SUBSTANCE: invention refers to coordination chemistry: specifically, to improved method of producing heterometal neodymium (III) and iron (III) malate of formula 1 to be used for synthesis of mixed oxides of perovskite composition. . Method is enabled by electrolysis of concentrated aqueous solution of neodymium (III) nitrate and malic acid in ratio 1:3 with pyridine or lithium perchlorate with anode added, pressed from recovered iron, and inert cathode from graphite with using pulse current of variable porosity. Thereafter the solution is evaporated with precipitation then washed with ethanol and dried.

EFFECT: method is cost-effective, controlled and productive.

3 cl, 3 tbl, 1 dwg

FIELD: chemistry.

SUBSTANCE: as catalyst substituted iron phthalocyanines of general formula ,

where R=[CH2N+(CH3)2CH2CH2OH]Cl-, L=(CH3)2NCH2CH2OH (I);

R=[CH2N+(CH3)2CH2CH2N(CH3)2]Cl-, L=(CH3)2NCH2CH2N(CH3)2 (III);

are used. Oxychlorination is carried out with mixture of H2O2 and HCl in water-alcohol medium in presence of suggested catalyst.

EFFECT: simplification of technology of obtaining chlor-derivatives of aromatic hydrocarbons with good yield and quality of product.

2 cl, 19 ex

FIELD: chemistry.

SUBSTANCE: agent is derivatives of bis(5-methylaminomethyluracil)polymethylene of formula (I) or pharmaceutically acceptable salts thereof

.

The agent is specifically a compound selected from: 5-[4-(2,4-dioxo-1,2,3,4-tetrahydro-5-pyrimidinylmethylamino)propylaminomethyl]-1,2,3,4-tetrahydro-2,4-pyrimidine dione (n=1); 5-[4-(2,4-dioxo-1,2,3,4-tetrahydro-5- pyrimidinylmethylamino)butylaminomethyl]-1,2,3,4-tetrahydro-2,4-pyrimidine dione (n=2);5-[4-(2,4-dioxo-1,2,3,4-tetrahydro-5- pyrimidinylmethylamino)pentylaminomethyl]-1,2,3,4-tetrahydro-2,4-pyrimidine dione (n=3) and 5-[4-(2,4-dioxo-1,2,3,4-tetrahydro-5- pyrimidinylmethylamino)hexylaminomethyl]-1,2,3,4-tetrahydro-2,4- pyrimidine dione (n=4). The disclosed compound was found to have in vitro capacity to increase activity of di- and polyamine oxidase, reduce ornithine decarboxylase activity, particularly in tumour cells, specifically tumour cells of human ovarian carcinoma. The disclosed compounds have in vitro low cytotoxicity. The invention also relates to a method of slowing down tumour cell proliferation using compounds of formula (1).

EFFECT: improved properties of inhibitor of formation of polyamines, low rate of tumour cells proliferation.

6 cl, 4 dwg, 11 tbl, 4 dwg

FIELD: medicine.

SUBSTANCE: treatment of oropharyngeal squamous cell carcinoma is ensured by drop-by-drop introduction of cetuximab 400 mg/m2 for the first day of the first week. Then from the first day of the second week, radiation therapy of large fractions 4 Gy is combined with introduction of cisplatin 30 mg for 3 days running. On the first day of the second to the fifth week, cetuximab 250 mg/m2 is introduced drop-by-drop. Further, a dose of radiation therapy is 2 Gy once a day, 5 times a week to total basic dose 30-40 Gy. In 2 weeks, the course is performed again to total basic dose 70 Gy according to the same scheme.

EFFECT: method allows increasing rate and degree of primary tumour regress, suppressing sub-clinical disseminated metastases, ensuring maximum anticancer effect without injuring normal tissue cells, enables preserving organ functions, increasing a number of organ-saving surgeries, improving quality of life of the patients, reducing invalidisation.

2 ex

FIELD: medicine.

SUBSTANCE: method involves introduction in a patient's body cyclophosphan, a preparation of a cytostatic group which is introduced in dose 20 to 100 mg/kg of body weight and a preparation of fragmented allogenic two-chained genomic DNA with fragments having a biologically active value and composing a full genome of physiologically and genetically healthy donor (hereinafter - exogenic DNA). The exogenic DNA preparation is introduced 48 hours after each introduction of the cytostatic preparation and for the following 30 days for the scheme when the patient has taken a full course dose 6-14 g, or for the following 3-5 days after a single injection and one day before a following injection with continuing with such intermittent to a complete setting of a therapeutic or supporting dose of the cytostatic preparation.

EFFECT: use of the invention allows higher clinical effectiveness in tumours ensured by differentiated inhibition of cytotoxic and regulatory lymphocyte viability under the effect of cyclophosphan and exogenic DNA.

3 tbl, 9 dwg

FIELD: medicine.

SUBSTANCE: group of inventions can be used for detection of epidermal growth factor receptor (EGFR) antibodies reducing or preventing signal transmission by intact EGFR or EGFRvIII. The methods under the invention include (a) contact of a candidate antibody with EGFR protein or its fragment having wild-type EGFR, (b) contact of the candidate antibody with EGFR protein or its fragment having mutant EGFR, comparison of binding of the candidate antibody with EGFR protein or its fragment, at the stage (a) with binding of the candidate antibody with EGFR protein or its fragment at the stage (b), and the antibody binding with EGFR at the stage (a), not at the stage (b) is identified as an anti-EGFR antibody which decreases or prevents signal transmission by intact EGFR or EGFRvIII.

EFFECT: use of inventions enables to identify the antibodies inhibiting signal transduction by intact EGFR.

19 cl, 9 dwg, 3 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: in order to stimulate anti-tumour activity of cytotoxic effectors of immune system into organism of person with tumour introduced are recombinant proteins, containing mini-antibody to tumour-specific antigens and molecule "БТШ70".

EFFECT: invention makes it possible to activate anti-tumour immune response, connected with NK-cell activation, due to targeted delivery to the surface of tumor cells of "БТШ70" molecules.

3 ex, 4 dwg

FIELD: medicine.

SUBSTANCE: intraoperationally introduced is fluoruracyl in dose 1000 mg/m and leukovorine in dose 100 mg/m after incubation with 100 ml of ozonised 400 mcg/l of autoblood intravenously. Oxaliplatin in dose 100 mg/m2 with 50 ml of ozonised 1000 mcg/l physiological solution is introduced into left gastric artery. Exposition of medications is 30 min. Gastrectomy is performed. After 7 days blood is sampled from patient in amount 100 ml in sterile vial with glugicir. Blood is bubbled. Concentration of ozone in ozone-oxygen mixture is 400 mcg/l. 100 mg/m2 of oxaliplatine are added and re-infused to patient intravenously, in drops. Next day 1000 mg/l of fluoruracyl and 100 mg/m2 of leukovorine are introduced successively intravenously, in drops with 100 ml of ozonised 400 mcg physiological solution. Treatment is repeated two times more with 3 week interval.

EFFECT: method makes it possible to prolong remission terms.

1 ex

FIELD: medicine.

SUBSTANCE: methods in accordance with invention relate to introduction of enantiomerically pure (+)-1,4-dihydro-7-[(3S,4S)-3-methoxy-4-(methyamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiasolyl)-1,8-naphthydirine-3-carboxylic acid in dose from 50 to 90 mg/m2 for treatment of myelogenous leukemia leukemia and in dose from 45 to 75 mg/m2 for treatment of ovary cancer.

EFFECT: extension of arsenal of medications for treatment of ovary cancer and myelogenous leukemia.

37 cl, 15 tbl, 20 dwg, 11 ex

FIELD: medicine.

SUBSTANCE: claimed is application of analogues of 39-desmethoxypapamicine of formula (I) in preparation of medication for treatment of pathology, affecting central nervous system, requiring medication crossing the hematoencephalic barrier (HEB) and where medication is intended for treating brain tumour, as well as medication for treatment of tumours or B-cell neoplasms, where tumour or B-cell neoplasm expressed P-glycoprotein and are resistant to one or more existing anti-tumour agents, and corresponding to last purpose pharmaceutical composition.

EFFECT: increased passage of compound through HEB, suppression of P-gp-expressing tumour cells, reduction of glioma growth.

18 cl, 9 dwg, 13 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: medication for photodynamic therapy (PDT) includes photosensitising substance based on hydrophilic chlorine E6 derivative, phosphatidylcholine, cholesterol, citric acid and saccharose with definite molar component ratio. Method of obtaining said medication includes dissolution of phosphatidylcholine and cholesterol in chloroform, mixing said solutions and further evaporation under vacuum until formation of film, which is dispersed with water solution of chlorine E6 derivative into liposomal dispersion. After that, into liposomal dispersion water solution of saccharose and citric acid with pH 5.0 is added and lyophilised, and immediately before intravenous introduction redispersed with application of distilled water or physiological solution. Method of carrying out PDT lies in systemic introduction of claimed medication and irradiation of pathologic section 4-5 hours after its introduction with optic irradiation, absorbed by chlorine E6. Claimed method of obtaining medication for PDT ensured increase of chlorine E6 derivative inclusion into said medication, increase of its stability in long storage and increase of its technological output.

EFFECT: high efficiency of photodynamic therapy and selectiveness of accumulation.

3 cl, 4 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: invention deals with application of trans-resveratrol nano-form as medication, possessing anti-proliferative properties with respect to hormone-dependent diseases. In particular, such diseases can be represented by: breast cancer, uterus and cervix cancer, fibromyomas, ovary cancer, endometrium cancer, endometriosis, adenomyosis, prostate adenoma, prostate cancer.

EFFECT: application of invention makes it possible to extend arsenal of medications for treatment of proliferative hormone-dependent diseases due to obtaining novel transport nano-form of trans-resveratrol.

2 cl, 4 dwg, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to complex compound of iron with carbohydrate. Complex compound, in addition to iron (III) contains iron (II). Per cent of iron (II) in terms of total amount of iron in complex compound constitutes, at least, 2 wt %. Carbohydrate is selected from group, consisting of natural carbohydrates or synthetic derivatives of carbohydrates, such as starch, hydrolysed starches, dextrins, in particular such as maltodextrin, maltose syrup, glucose syrup, cyclodextins, dextrans, saccharides. Per cent of carbohydrate in terms of complex compound of iron with carbohydrate constitutes from 10 to 80 wt %. Method of obtaining complex compound of iron with carbohydrate includes the following stages. Water solution of suspension of carbohydrate is prepared. After that, iron (III) salts are added at constant pH value within the range from 7 to 13. Iron (III) salt is selected from group, consisting of iron (III) chloride and iron (III) sulfate. Water solution or suspension is heated with further cooling. Formed complex compound of iron with carbohydrate if isolated. Precipitation of complex compound of iron with carbohydrate is performed by addition of one or more alcohols, such as ethanol or propanol. Obtained complex compound is used for production of medication for treatment of iron-deficient anemias, which is well absorbed in organism in case of peroral intake.

EFFECT: iron, included into composition of medication is better resorbed and better tolerated by organism than pure iron preparations.

26 cl, 1 tbl, 4 ex

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