The method of obtaining complexes of transition metals
(57) Abstract:Usage: as radiopharmaceutical products or in the synthesis of radiopharmaceutical products. Entity: an improved way of obtaining complexes of transition metals selected from the group of:99mTe186Re ,188Re containing nitride group: M-N, where M is Tc,186Re,188Re . Reagent 1: compound of the transition metal pertechnetate or perinat alkali metal or ammonium. Reagent 2.: the first ligand - postsin General formula where R1, R2, R3- same or different and denote phenyl, which may be substituted by CN, sulphonate group, a lower alkyl which may be substituted by cyano. Reaction conditions: reagent 1 is subjected to interaction with the first ligand is a phosphine of the formula 1: where R1, R2, R3- same or different and denote phenyl, which may be substituted by cyano group, a sulphonate group and the second ligand is a nitrogen - containing compound selected from the compounds of formula II where R4is hydrogen, lower alkyl, R5lowest alkylthiomethyl, where Z Is O,S, R H, lower alkyl, NH2or Z is NH, R is H or COR , where R is lower alkoxy, lower alkyl, furyl, oxetanyl or soy the azide of an alkali metal, or ammonium , and, if necessary, with the third ligand from the group of compounds of the formula where R8- R9- , (CH2)2NH2or halide-di-lower alkylphosphonate, or hydrohalogen of mercaptoquinoline, in aqueous solution at a molar ratio of nitrogen-containing ligand to the peroxide compound is 1: 10-9- 10-4. 1 C.p. f-crystals, 3 tables. The invention relates to methods for transition metal complexes that can be used as radiopharmaceutical products as such or in the synthesis of new radiopharmaceutical products.More specifically, the invention relates to the production of nutrigenomics transition metal M selected from the99mTc 186Re and188Re containing the group MN, where M stands for99mTc 186Re and188Re.These complexes of transition radioactive metals are used as pharmaceutical products for radiodiagnosis and radiotherapy.A method of obtaining radiopharmaceutical products based on complexes of technetium - 99m containing the group (Tc N)2+(see J. Chem.Soc. Dalton. Trans. 1981, pp. 1798-1801), which consists in the interaction of the compounds of formula R+M. However, this method is long, as mentioned source includes at least three stages. In addition, this method does not guarantee the sterility and apyrogenicity of the obtained product.From the document Isotopenpraxis, 1981, pages 174-175 is also known interaction pertechnitat99mTC sodium with ligands, for example, triphenylphosphine and diclorhidrato hydrazine; carried out in an organic solvent, such as benzene, ether, acetone. However, as returned by this method the complex is not pharmaceutically suitable product, and is used as a catalyst for the reduction reaction of elemental nitrogen into ammonia.The purpose of the invention is to develop a more simple way of obtaining complexes of radioactive metals with obtaining sterile and pyrogen-free pharmaceutically suitable product.This goal is achieved by the proposed method to obtain nutrigenomics transition metal selected from the group of:99mTc186Re and188Re, which lies in the interaction of peroxy compounds of the transition metal with the appropriate ligand and characterized in that the peroxide compound is transient the action with the first ligand is a phosphine of General formula I
PR2where R1, R2, R3- same or different denote phenyl, possibly substituted by cyano or sulfonic group, and lower alkyl, possibly substituted by cyano, and with the second ligand is a nitrogen - containing compound selected from the group: azide of alkali metal or ammonium, and the compounds of formula II:
H2N-N where R4is hydrogen, lower alkyl,
R5is hydrogen, lower alkylthiomethyl, group:
CHR , where Z means oxygen atom or sulfur,
R" is hydrogen, lower alkyl, NH2or Z signifies NH, R" is hydrogen or -- COR"', where R"' is lower alkoxygroup, lower alkyl, furyl, oxetanyl; or the compounds of formula III
R7-CH= N-N where R4- has the above meanings;
R7oksifenil, pyridyl, and, if necessary, with the third ligand selected from the group of compounds of the formula
C-C where R8= R9means C(CH3)2SH, (CH2)2NH2; or hydrohalogen di-lower alkylphosphonate or hydrohalogen of mercaptoquinoline, in aqueous solution at a molar ratio of nitrogen-containing ligand to the peroxide compound is equal to 1:(10-9- 10-4).For prakticheskoj is respectfully in aqueous solution, and then, after adjusting the pH to a desired value by using acid or alkali, add the required amount of peroxide compound of the transition metal, for example, pertechnitat technetium 99m. The reaction is carried out at room temperature or at a temperature higher by 50 to 100aboutC. Temperature and pH value depends on the type of the second ligand. Typically operate at pH below 4.The resulting product is suitable for use as a radiopharmaceutical product in therapy or diagnosis. To obtain nutrigenomics with enhanced tropism for certain organs of the human body obtained nutrigenomics technetium subjected exchange reaction with the third ligand.This exchange reaction can be carried out simultaneously, preferably in aqueous solution with formation of nutrigenomics by the interaction of all components: peroxide compounds transition metal, the first ligand, the second ligand and second ligand, which is used as the organic compound with the nucleophilic group, a monoclonal antibody or antibody fragment.It is possible to conduct the reaction in two stages: the first stage carried out Predoctoral ligands, and in the second stage, the interaction of the product obtained in the first stage, with the third ligand selected from the monoclonal antibodies or fragments of antibodies, also preferably in aqueous solution.This exchange reaction can be carried out in an alcohol or water-alcohol solution; you can also first and second stage in various solutions, for example, the first phase in an aqueous solution, and the second phase - in alcoholic or aqueous-alcoholic solution or Vice versa.Organic ligands with nucleophilic groups can be very diverse. For example, it is possible to use amines, thiols, thioethers, oximes, phosphines, and polyfunctional ligands of type polyaminopropyl.For implementing the method in a hospital setting it is enough to position the kit comprising a first vial containing a first ligand phosphine type, and a second vial containing the second nitrogen-containing ligand.Mix the contents of two vials and add, for example, a solution of sarahnet alkali metal or ammonium. The first and second ligand can be respectively in the first and second vials in liquid form or in liofilizirovannom.In n the removed solution of peroxide compounds transition metal, for example, pertechnitat or perrenate for receiving radiopharmaceutical product.As mentioned above, you can use the complex transition metal obtained from the first and second ligand, as an intermediate product to obtain further another nutrigenomics transition metal by exchange reaction with the third ligand is a monoclonal antibody or antibody fragment.The product resulting from this reaction can also be used as such as a radiopharmaceutical product or for the diagnosis or therapy. In this case, a kit for preparing a radiopharmaceutical product may include a third vial containing a third organic ligand with nucleophilic groups, a monoclonal antibody or antibody fragment.P R I m e R 1. In penitsillinovy vial injected with 0.4 ml of a solution containing 210-2mol/l (2.5 mg/ml) S-methyldithiocarbamate (second ligand) in ethanol, and then 0.2 ml of a solution containing 210-2mol/l (5 mg/ml) of triphenylphosphine (first ligand) in ethanol, and 0.1 ml of 1 N. chlorotalonil acid. Then add 0.5 to 1 ml pertechnitat sodium (Tc-99m), (10-6- 10-11P R I m e R s 2-13. Work according to the method of example 1 and obtained from the ligand listed in table.1 nutrigenomics technetium, entering into the vial 510-3- 110-2mmol second ligand, 410-3mmol first ligand and 0.1 ml of 1 N. HCl and then adding 0.5 to 1 ml pertechnitat sodium.Chromatographic analysis of the products shows that we are talking about nitrido complexes containing the center TCN.P R I m e R 14. In penicillin vial injected with 0.4 ml of an alcohol solution of the second ligand, consisting of a solution with a concentration of 2.5 mg/ml (1.1 x x10-2mol/l) S-methyl-beta-N-(2-hydroxyphenyl) methylenecyclobutane in ethanol, 0.2 ml of a solution containing 5 mg/l (210-2mol/l) of triphenylphosphine (first ligand) in ethanol and 0.1 ml of a 1 N. chlorotalonil acid.Then add 0.5-1 ml of sterile solution pertechnitat sodium (technetium - 99m), the corresponding radioactivity from 18 Bq M to 3.7 GBq (0.5 to 100 mG), then heat the flask at 80aboutC for 30 minutesChromatographic analysis in a thin layer in the opposite phase, using as solvent a mixture of methanol, acetonitrile, and then it is carbonated is her group TcN.P R I m e R s 15-22. Repeat the procedure of example 14, but with the first and second ligands are listed in table. 2, entering into the vial 110-2- 310-3mmol second ligand, 410-3mmol first ligand and 0.1 ml of 1 N HCl and then adding 0.5 to 1 ml pertechnitat sodium Tc-99m. At the end of the operation, the resulting product is subjected to chronographie in a thin layer, which indicates that the complex contains a group TN and that phosphine is an integral part of the received complex.P R I m e R 23. Working as described in example 1, but using as the second ligand 4-methyl-3-thiosemicarbazide formula
CH3-NH--NH-NH2Chromatographic analysis of the product shows that the resulting complex is nutrigenomics technetium and that it contains triphenylphosphine.P R I m e R 24. In this example, followed by the method of example 14, but using as the second ligand aminoacetonitrile formula
H2N--NH-N= H2-NH2< / BR>Chromatographic analysis in a thin layer shows that the resulting complex is nutrigenomics technetium.P R I m e R 25. In this example, is injected into the vial with 1 ml of a solution containing 510-3mol/l alpha-N-methyl-S-methyl-beta-N - (2-gidrol-phosphino)ethane of the formula:
(CH3)2P-CH2-CH2-P(CH3)2and 0.1 ml of 1 N. chlorotalonil acid. Then add 0.5 ml of sterile solution pertechnitat sodium (Tc-99m) vial and heated at 80aboutC for 30 minutesGet nutrigenomics technetium containing a first ligand-based diphosphine.P R I m e R 26. Work the same as in example 25, but using a solution containing 510-3mol/l bis(1,2-dificil-phosphine)ethane and the solution 510-3mol/l alpha-N-methyl-S-methyl-beta-N - (2-hydroxy - phenyl) methylenecyclobutane.Get nutrigenomics technetium containing diphosphinic ligand.P R I m e R 27. In this example, preparing a complex of rhenium-186, entering into the vial penicillin type 7 mmol of triphenylphosphine and 2 mmol of alpha-N-methyl-S-methyl-beta-N - (2-hydroxyphenyl) methylenecyclobutane in an alcohol solution and 5 mmol of 1 N. chlorotalonil acid. Then enter 1 mmol of perrenate sodium and carried out at 40aboutC for 30 minutesGet nutrigenomics rhenium with output above 90%. In the following examples use nutrigenomics technetium obtained in the previous examples for other complexes of technetium used as a diagnostic cont what about the complex of technetium with the third ligand, which is the compound 1,1-(1,2-atendimento (bis-(2-methyl-2-propanethiol) formula
C To the contents of the bottle obtained in example 14, add 0.2 ml of a solution containing 410-2mol/l of 1,1'-(1,2-tenderlionne)-bis(2-methyl-2-propanethiol) in ethanol.Bring the pH to 9.5 by adding 0.5 ml of buffer solution, carbonate/bicarbonate concentration of 0.5 M and heat the bottle up to 80aboutC for 30 minutesThe resulting product analyzed by chromatography in thin layer using silica gel and a solvent mixture of ethanol, chloroform and benzene (2: 2: 1). The location of the chromatographic spots corresponds to nutrigenomics technetium containing group TcN; Rf = 0,44 (silicon oxide, ethanol/chloroform/benzene).Comparative example 1.Interact solution of 1,1'-(1,2-tenderlionne) bis-(2-methyl-2-propanethiol) pertechnitat sodium (Tc-99m) in the presence of chloride of tin. Get diaminopimelate Ecotechnie that analyze thin-layer chromatography under the same conditions as the product in example 27.The location of the chromatographic spots obtained complex of technetium center (TSS)3+different from the location of these spots nitri is Holocene other nutrigenomics technetium, on the basis of the products obtained in examples 1, 2 and 16-21 and using as the third ligand compound 1,1'-(1,2-tenderlionne)-bis-(2-methyl-2-propanethiol).In all cases receive nutrigenomics technetium containing the third ligand. Rf = 0,44 (silicon oxide, ethanol/chloroform/benzene).P R I m e R 37. Work similarly to the method of example 28 to obtain a new complex of technetium from the product obtained in example 1, but using as the third ligand solution containing 610-2mol/l of tetrataenia formula
< / BR>Get a new nutrigenomics technetium containing as a ligand tetrathionate Rf = 0,61 (cellulose, ethanol, ammonium acetate).The purity of the obtained product was determined by thin-layer chromatography using cellulose and solvent-based ethanol-ammonium acetate 0.15 M ratio (4:3).P R I m e R s 38-45. Follow the procedure of example 37, by adding to the product obtained in examples 2, 14, 16-21 0.2 ml of a solution containing 610-2mol/l Tetra - asoundconf.In all cases receive nutrigenomics technetium containing the ligand tetrathionate. Rf = 0,61 (cellulose, ethanol, ammonium acetate).P R I m e R 46. To stereomate bis(1,2-dimethylphosphino)ethane (DMPE). Bring the pH to 10 by adding 0.5 ml of buffer solution of bicarbonate/carbonate with a concentration of 0.5 mol/l and carry out the reaction at 80aboutC for 30 minutesThe resulting product analyzed by thin-layer chromatography (cellulose; solvent - ethanol - ammonium acetate, 0,015 M; 4:3). The analysis confirms the receipt of nutrigenomics technetium containing the third ligand. Rf = 0.75 in (cellulose, ethanol, ammonium acetate).So chromatographic spots related to this complex differ from those obtained with the known complex of technetium with formulas
99mTcCl2DMPA2+and 99mTcO2DMPA2+< / BR>P R I m e R 47. Obtaining complex99mTc N containing 8-mercaptoquinoline.A. Obtaining an intermediate product.In the vial penicillin-type injected with 0.2 ml of a solution containing 7,710-2mol/l (5 mg/ml) of sodium azide in water, and then 0.5 ml of a solution containing 5,210-3mol/l (1 mg/ml) of Tris(2-cyanoethyl)-phosphine in water.Then add 0,5-5 ml pertechnitat sodium (99mTc) and conducting the reaction at 80aboutC for 30 min or at 100aboutC for 15 minutesB. Receiving target complera carbonate-sodium bicarbonate concentration of 0.5 mol/l to pH 9.0 and 0.4 ml of solution, containing 510-2mol/l hydrochloride 8-mercaptoquinoline (10 mg/ml) in ethanol.The reaction is carried out for 15 min at 100aboutC, 30 min at 80aboutC or 60 min at room temperature.Radiochemical purity of the obtained complex was determined by chromatography in thin layer using silica gel and a solvent mixture of ethanol, chloroform, toluene and ammonium acetate (0.5 M) in the ratio 6:3:3: 1.The resulting complex has a Rf = 0.95, and while99mTcO4- indicator Rf = 0,5.Radio purity above 95%.P R I m e R 48. Obtaining antibodies, labeled intermediate complex TN.a) Obtaining an intermediate product.In the vial penicillin-type injected with 0.4 ml of a solution containing 210-2mol/l (2.7 mg/ml) S-methyl-N-methyldithiocarbamate in the water, and then 0.5 ml of a solution containing 5,210-3mol/l Tris(2-cyanoethyl)phosphine in water and 0.1 ml and 1 N. chlorotalonil acid. Then add 0.5 to 5 ml, pertechnitat sodium (99mTC) and conducting the reaction at 80aboutC for 30 min or at 100aboutC for 15 minutesb) Obtaining labeled antibodies.The contents of practical anti-ACE (anti-antigen, carcinoembryonic), the pre-treated mercaptoethylamine for activation of sulfhydryl groups in a buffer solution of 0.1 M phosphate with a pH of 7.0.The reaction proceeds for 30 min at 35aboutC.Radiochemical purity determined by chromatographic method by filtration through a gel column TSK type G 3000 SW (0,75 x 30 cm) using phosphate tampon 0.1 M pH 7.0 at a speed of 1 ml/min was recorded Simultaneously radioactivity and absorption capacity of the sample.95% elyuirovaniya radioactivity detected between 7 and 7.8 ml, and the designated number of99mTCO4with 12 ml is less than 5%.P R I m e R s 49-55. In these examples, we study the properties of the complexes obtained in examples 2, 14, 17, 21, 28, 37 and 47, by bearsdley in male rats breed Sprague Dawley weighing 200+20, For this purpose, rats, shot by pentobarbital, enter the product dose from 3.7 q to 10 q (1-2,7).Animals wortlaut after 5 min after administration of the product. Authorities seized washed and measure their radioactivity on scintigraphically the counter.The results are shown in table.3. The results are expressed as percentages of induced reactivity detected the. The METHOD of OBTAINING COMPLEXES of TRANSITION METALS selected from the group99mT186Re ,188Re containing nitride group of the General formula where M is Tc , 186Re ,188Re possessing radiopharmaceutical properties, the interaction of peroxy compounds of the transition metal with the appropriate ligand, characterized in that the peroxide compound of the transition metal used pertechnetate or perinat alkali metal or ammonium, which is subjected to interaction with the first ligand is a phosphine of General formula
< / BR>where R1, R2, R3the same or different, is a phenyl which may be substituted by CN, sulphonate group, a lower alkyl which may be substituted by cyano,
and with the second ligand is a nitrogen - containing compound selected from the compounds of General formula
< / BR>where R4is hydrogen, lower alkyl;
R5is hydrogen, lower alkylthiomethyl, where Z Is O, S; R" is hydrogen, lower alkyl, NH2or Z is NH, R" is hydrogen or COR"', where R"' is lower alkoxy, lower alkyl, furyl, oxyphenyl,
or compounds of General formula
< / BR>where R4has the specified values;
R7oksifenil,s compounds of General formula
< / BR>where R8= R9- C(CH3)2SH, (CH2)2NH2< / BR>or hydrohalogen di-lower alkylphosphonate, or hydrohalogen of mercaptoquinoline, in aqueous solution at a molar ratio of nitrogen-containing ligand and peroxide of 1 : 10-9- 10-4.2. The method according to p. 1, wherein the first ligand using triphenylphosphine or diethylphosphine.Priority signs
15.11.88 first ligand is a phosphine, in which R1and/or R2is phenyl or alkyl substituted by CN-group, the second ligand - azide of alkali metal or ammonium, the third ligand - hydrogenogenic of mercaptoquinoline.09.05.88 - all other values specified in the formula.
FIELD: organic chemistry, medicine, physiology.
SUBSTANCE: invention relates to agents for regulation (maintaining or suppression) of physical working ability and/or adaptation to different variants represented by solvated complex compounds of the general formula (I): Katm+[L1 qEL2]Ann- x p.Solv (I) wherein L1 means aminothiols of the formula: R1NHCH(R2)(CH2)1-2SR3 wherein R1 means hydrogen atom (H), (C1-C20)-alkyl or RCO; R means (C1-C19)-alkyl; R2 means H or carboxyl; R3 means H, (C1-C20)-alkyl, (C2-C20)-alkenyl or benzyl; q = 1, 2 or 3; L2 means halogen atom, water and/or organic ligand. For example, bis-(N-acetyl-L-cysteinato)aquozinc (II) diheptahydrate suppresses physical working ability and in the dose 50 mg/kg increases reviving time of mice by 6 times and cats - by 2.8fold under conditions of acute hypoxia with hypercapnia, and increases reviving time of mice by 4 times under conditions of acute hypobaric hypoxia. Under the same conditions the known antihypoxic agents amtizol, acizol or mexidol are inactive or less active significantly by their activity. Bis-(N-acetyl-L-cysteinato)-ferrous (II) pentahydrate is more active as compared with the known antihypoxic agents and protects experimental animals in 4 variants of hypoxia. Bis-(N-acetyl-L-cysteinato)zinc (II) sulfate octahydrate is similar to enumerated compounds by its antihypoxic activity.
EFFECT: valuable medicinal properties of compounds.
4 cl, 1 dwg, 11 tbl, 33 ex
FIELD: catalyst preparation methods.
SUBSTANCE: invention relates to preparation of manganese (III) acetylacetonate, which can be used as catalyst as well as vinyl monomer polymerization initiator. Method is implemented in aqueous medium with ammonium acetylacetonate freshly prepared by mixing acetylacetone with aqueous ammonia solution. Hydrogen peroxide is used as oxidant and sodium bicarbonate is additionally introduced into reaction mixture. Following consecutive operations are carried out: reaction of manganese (II) chloride tetrahydraye with sodium bicarbonate; separating thus formed manganese (II) bicarbonate in the form of paste; adding ammonia acetylacetonate and then hydrogen peroxide aqueous solution to the paste; and recovering manganese (III) acetylacetonate with yield 95%.
EFFECT: improved economical and environmental characteristics of process.
FIELD: chemical technology.
SUBSTANCE: invention relates to technology for synthesis of acetic acid inorganic salts. Method involves interaction of metallic manganese or its dioxide with acetic acid in the presence of oxidizing agent. Process is carried out in beaded mill of vertical type fitted with reflux cooling-condenser, high-speed blade mixer and glass beads as grinding agent loaded in the mass ratio to liquid phase = 1.5:1. Liquid phase represents glacial acid solution in ethylcellosolve, ethylene glycol, 1,4-dioxane, isoamyl alcohol and n-butyl alcohol as a solvent. The concentration of acid in liquid phase is 3.4-4 mole/kg. Then method involves loading iodine in the amount 0.025-0.070 mole/kg of liquid phase, metallic manganese and manganese dioxide in the mole ratio = 2:1 and taken in the amount 11.8% of liquid phase mass. The process starts at room temperature and carries out under self-heating condition to 30-38°C to practically complete consumption of manganese dioxide. Prepared salt suspension is separated from beads and unreacted manganese and filtered off. Filtrate is recovered to the repeated process and prepared precipitate is purified by recrystallization. Invention provides simplifying method using available raw and in low waste of the process.
EFFECT: improved method of synthesis.
3 cl, 9 ex
FIELD: chemical industry; methods of production of the bromine derivatives of fullerene С60.
SUBSTANCE: the invention is pertaining to the method of production of the bromine derivatives of fullerene С60. The process consists in the interaction of the bromoform and the tetra bromomethane with fullerene С60 at presence of the rhodium-containing catalyst - Wilkinson's complex [RhCl(PPh3)3] at the temperature of 100°С within 10-20 hours, at the molar ratio of [Rh]:[C60]:[CHBr3 or CBr4]= 1:100:100-500. The technical result of the invention is the increased output of the product, the reduced amount of the wastes, the insignificant consumption of the catalyst.
EFFECT: the invention ensures the increased output of the product, the reduced amount of the wastes, the insignificant consumption of the catalyst.
3 ex, 1 tbl
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to an improved solid-phase method for synthesis of radioisotope indicators, in particular, for synthesis of compounds labeled with 18F that can be used as radioactive indicators for positron- emission tomography (PET). In particular, invention relates to a method for synthesis of indicator labeled with 18F that involves treatment of a precursor fixed on resin if the formula (I): SOLID CARRIER-LINKER-X-INDICATOR wherein X means a group promoting to nucleophilic substitution by a definite center of a fixed INDICATOR with 18F- ion for preparing a labeled indicator of the formula (II): 18F-INDICATOR; to compound of the formula (Ib):
and compound of the formula (Ih): ;
to radiopharmaceutical set of reagents for preparing indicator labeled with 18F for using in PET; to a cartridge for radiopharmaceutical set of reagents for preparing indicator labeled with 18F for using in positron-emission tomography.
EFFECT: improved method of synthesis.
13 cl, 1 sch, 3 ex
FIELD: chemical industry; methods of production of the manganese salts with the organic acids.
SUBSTANCE: the invention is pertaining to production of the manganese salts with the organic acids in particular, to the salt of the divalent manganese and formic acid. The method is exercised by interaction of manganese, its oxides in the state of the highest valence with the formic acid solution in the organic solvent in the presence of iodine as the stimulating additive. The production process is conducted in the bead grinder of the vertical type having the revertive cooler-condenser, the high-speed paddle stirrer and the glass beads of in the capacity of the grinding agent loaded in the mass ratio to the loading of the liquid phase as (1÷2): 1. The liquid phase consists of the formic acid solution in the organic solvent. The concentration of the acid is taken within the range of 3.5÷10.8 mole/kg. In the loaded liquid phase they dissolve the stimulating additive of iodine in the amount of 0.025-0.100 mole/kg of the liquid phase. The ratio of the masses of the liquid phase and the total of the metallic manganese and the manganese oxide are as(4.9÷11):1. The molar ratio of the metal and the oxide in the loading is as (1.8÷2.,2):1. The metal and the oxide are loaded the last. It is preferable in the capacity of the dissolvent to use the butyl alcohol, ethyl acetate, ethylene glycol, 1.4-dioxane, dimethyl formamide. The production process is started and conducted at the indoor temperature up to practically complete(consumption of the whole loaded manganese oxide. Then the stirring is stopped, the suspension of the salt is separated from the beads and the nonreacted manganese and after that conduct filtration. The filtrate and the nonreacted manganese are returned into the repeated production process, and the filtered out settling of the manganese salt is exposed to purification by recrystallization. The technical result of the invention is - simplification of the method at usage of accessible reactants.
EFFECT: the invention ensures simplification of the method at usage of accessible reactants.
16 ex, 2 tbl
SUBSTANCE: invention is related to improved method for preparation of manganese oxalate (II) by means of direct interaction of metal with acid in bead mill in presence of liquid phase, in which manganese and oxalic acid are loaded into bead mill in stoichiometric ratio in amount of 0.75-2.4 mole/kg of load at mass ratio of load and glass beads of 1:1.2, liquid phase dissolvent used is water or organic substance, or mixture of organic substances; loading is carried out in the following sequence: liquid phase dissolvent, acid, then metal; process is started at room temperature and is carried out under conditions of forced cooling in the temperature range of 18-39°C with control over procedure by sampling method to practically complete spend of loaded reagents for product making, afterwards mixing and cooling are terminated, suspension of reaction mixture is separated from glass beads and filtered, salt deposit is sent for product cleaning from traces of non-reacted metal, and filtrate is returned into repeated process.
EFFECT: method makes it possible to produce target product in absence of manganese dioxide and stimulating additive at temperatures close to room temperature.
2 cl, 13 ex, 2 tbl
SUBSTANCE: invention refers to chelating agents and their technetium complexes to be used as radiopharmaceuticals and characterised by formula I where X is -NR-, -CO2-, -CO-, -NR(C=S)-, -NR(C=O)-, -CONR- or Q; Y represents amino acid, -CH2-, -CH2OCH2-, -OCH2CH2O- or X; Z is an aggregation from peptides, their analogues, substrata, antagonists or enzyme inhibitors, receptor-bonding compounds, oligonucleotides, oligo-DNA- or oligo-RNA-fragments; n is a number 1 to 8; m is a number 0 to 30; R represents H, C1-4alkyl, C2-4alkoxyalkyl, C1-4hydroxyalkyl or C1-4fluoroalkyl; Q represents remains of succinimide , A is a pharmaceutically acceptable anion.
EFFECT: production of new chelating agents applicable for making the technetium complexes.
22 cl, 12 ex, 3 dwg, 2 tbl
SUBSTANCE: invention relates to an improved method of producing manganese (II) fumarate from manganese metal and its oxide (III) through direct reaction of the metal and its oxide Mn2O3 with an acid in the presence of a liquid phase and a stimulating iodine additive in a vertical type bead mill with glass beads as grinding agent. The metal and its oxide are loaded in molar ratio (2±0.1):1 in total amount of 7.87 to 10.93% of the mass of the load. Acid is added with 15 to 25% excess of the calculated value, equal to the number of moles of metal and twice the number of moles of metal oxide in the load. The base of the liquid phase is isoamyl alcohol, in which the iodine stimulating additive is dissolved in amount of 0.02 to 0.05 mol/kg. Glass beads are loaded first, in mass ratio to the reaction mixture of 1.35:1, and then later the liquid phase solvent, acid and stimulating additive, and after brief stirring, metal oxide and metal, stirring all the while. Taking this moment as the beginning of the process, forced cooling is introduced right away. Operating temperature is stabilised in the range 33 to 45°C and in this mode, the process is carried out until virtually quantitative conversion of metal and its oxide to the target salt, after which stirring and forced cooling are stopped. The reaction mixture is separated from the glass beads, cooled to temperature 5 to 6°C and kept at that temperature for 1 to 2 hours. The solid phase of the target salt is filtered off and washed with isoamyl on a filter cooled to approximately the same temperature, after which it is taken for purification by recrystallisation. The filtrate and the cleaning solvent, containing excess acid, the bulk of the stimulating additive and a certain amount of dissolved target salt, are returned for loading in the repeated process. The process is carried out in light temperature conditions. The target substance can be easily separated.
EFFECT: design of a low-waste method, which allows for obtaining target product from available manganese oxide with an easy to implement process.
SUBSTANCE: method of synthesis of manganese (II) fumarate through direct reaction of metal with acid is presented. The process is carried out in a vertical type bead mill with mass ratio of beads to the reaction mixture equal to 1:1, and the liquid phase is a solution of fumaric acid in an organic solvent with content of acid of 0.70-1.80 mol/kg. Manganese is taken in stoichiometric amount with acid or in deficiency of up to 5%. The process is started by loading the liquid phase solvent and acid and preparation of the acid solution in a bead mill, after which metal is loaded and the process is carried out at temperature ranging from 25 to 35°C while preventing spontaneous increase of temperature through forced cooling and controlling through sample taking and determination of manganese salt in the samples and residual amount of acid until attaining values close to calculated values during quantitative conversion of the reagent in deficiency. After that stirring and cooling are stopped. The suspension of the reaction mixture is separated from the glass beads, cooled to temperature between 5.2 and 6.2°C and filtered. The filtering residue is washed with the liquid phase solvent, cooled to approximately the same temperature, and taken for purification by recrystallisation. The filtrate and the washing solvent are returned to the repeated process.
EFFECT: method is easy to implement, the end product can be easily separated and there are no auxiliary materials which contaminate the obtained product.
2 cl, 11 ex