Alpha-crystalline form of substituted selenoxanthenes and method of producing said form

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry, particularly to the technology of producing selenoxanthenes and can be used in producing food additives, medicinal agents and cosmetic agents, which exhibit broad biological activity. An agent is described, which is an α-crystalline form of 9-phenyl-sym-octahydroselenoxanthene, which has antixodant, detoxication, immunomodulating, antiatherogenic, antisclerotic, anabolic, hypolipid action, and the corresponding structural formula with powder X-ray pattern obtained on Cu-K radiation sources with characteristic reflection indices expressed in degrees of the diffraction angle 2θ: 6.0 12.0 15.0 17.0 19.0 20.0 21.5, 21.7, 20.9 25.0 27.0 28.0 29.0 37.0 and melting temperature 96.8°C, as well as to a method of producing said agent, involving crystallisation of the corresponding 9-R-sym-hydroselenoxanthene from low-polar or non-polar solvent, preferably hexane, chloroform or isopropyl alcohol.

EFFECT: design of an efficient method of producing selenoxanthenes.

3 cl, 1 dwg, 1 tbl


The invention relates to organic chemistry, medicine, pharmacology, food and cosmetic industries, in particular to a technology for production of selenocysteine, and can be used in the production of food additives, drugs and cosmetics exhibiting biological activity, a wide spectrum of action.

Substituted selenocysteine known (RU 2213092, EN 2239632). Their structural formula looks

So far replaced selenocysteine received mainly in the amorphous form. The disadvantage of amorphous form is unstable during storage. The substance has a low flowability, prone to caking.

Selenolate and the methods of its production are disclosed, for example, in patent RU 2213092, EN 2239632, EN 2281007. In these publications indicate that the received selenolate can be recrystallized from ethanol or acetone.

The use and activity of the compounds disclosed in these publications, in particular in EN 2281007. According to this patent, 9-phenyl-s-octahydrophenanthrene has antioxidant, detoxifying, gipolipidemiceski, immunomodulatory, immunocorrection, antiatherogenic, antiateroskleroticescoe and anabolic effects. According to the data obtained from the report on determination of toxicologica the fir characteristics of selenocysteine /Laboratory BAS Belgorod agricultural Academy, K. wetney. Overall, 1996/, is replaced by selenolate has acute toxicity after intragastric administration at the level of LD50=725+75 mg/kg All this limits the scope of substituted selenocysteine, including as substances for dietary supplements and pharmaceuticals.

The authors have solved the problem of obtaining non-toxic substituted selenocysteine, stable during storage and has good flowability.

To solve this problem is proposed remedy represents selenolate α-crystal modification with a powder x-ray obtained at the Cu-K a radiation source with parameters characteristic of reflection expressed in degrees of diffraction angle 2θ: 6,0 12,0 15,0 17,0 19,0 20,0 21,5, 21,7, 20,9 25,0 27,0 28,0 29,0 37,0, below the drawing.

Powder diffraction pattern was obtained on a diffractometer "Bruker D8 Advance" (T=298 K, λCu Kα-radiation, mirror Goebel, θ/2θ scans with a step of 0.02°).

Description of the experiment

X-ray diffraction study. Crystal connection N (C19H22Se1M=329.33), tetragonal, space group P 421c, at T=100 To a=b=19.5515(15)Å, C=8.0074(6)Å, V=3060.9(4)Å3Z(Z')=8(1), F(000)=1360, dcalc=1.429 g•cm-3, µ=at 24.42 mm-1. Intensity 12199 reflections measured on an automatic diffractometer "Bruker SMART APEX II CCD" (T=100 K, The Mo-α-radiation, graphite monochromator φ - and ω-scans, θmax=58°) and further calculations were carried out on 4063 independent reflections (Rint=0.0444). Accounting for the absorption of x-rays was performed according to the program SADABS1. The structure is defined by the direct method and refined by full-fabric by the least squares method in the anisotropic approximation for non-hydrogen atoms. Position of hydrogen atoms calculated geometrically and they are all refined in isotropic approximation with fixed position (model "rider") and thermal parameters. The final factors of divergence equal to R1=0.0306 for 3506 independent reflections with I > 2σ(I) and wR2=0.0614 and GOF=0.999 for all independent reflections. All calculations were performed using complex programs SHELXTL PLUS (Version 5.10)2.

The product is obtained in the following way. The amorphous powder obtained by known techniques, crystallized either from a polar solvent selected from the group consisting of methanol, isopropanol, any of the aprotic solvent selected from the group consisting of chloroform, and hexane.

To prove the achievement of the technical result, it is possible to provide data for evaluation of acute toxicity of the proposed substance. In the course of its General toxic studies have not found toxic effects at once the rats intragastrically, at a dose of 1000 mg/kg animal body weight, which is more than 1000 times the average therapeutic dose.

Results on the determination of physico-chemical data of amorphous and crystalline forms are presented in the table:

The angle of repose, °Melting point,°CShelf life, monthsAppearance
The substance of the patent RU 2281007 (acetone)52°95-96°6Beige, powder
Crystalline form (hexane)43°96.8°24Yellow needle crystals

The method is as follows.

To obtain 9-(o-oxyphenyl)-SIMM-octahydrophenanthrene took 12.5 g of 9-(o-oxyphenyl)-octahydro-10-oaxacana and were placed in a three-neck flask with a magnetic stirrer and with a supply of gas. Then added 30 ml of a mixture of acetic acid:acetic anhydride (4:1). With stirring, the reaction mixture was purged with nitrogen for 30 minutes, then a stream of nitrogen was stopped and missed in the reactions is nnow mixture and hydrogen selenide. 30 minutes after the start of transmission of the selenide in the reaction mixture at intervals of 1 hour twice was added 1.0 ml of concentrated hydrochloric acid. The bandwidth of the selenide was 2-3 bubble per second. The total time of transmission of the selenide was 6 hours, after its completion, the reaction mixture was purged with nitrogen for 40 minutae the reaction mixture was placed in a refrigerator and the next day the precipitation was filtered, washed with acetic acid and alcohol. The product yield was 11.5,

Example 1

For recrystallization took 10 g of amorphous product was placed in a flask with a capacity of 250 ml, was added 85 ml of hexane, brought to the boil, filtered hot solution. After the loss of their crystals filtered off, washed with cold alcohol and dried at 40°C. Yield is 8.7, Tpl.- 96.8°C.

Example 2

For recrystallization took 10 g of amorphous product was placed in a flask with a capacity of 500 ml, was added 250 ml of isopropanol, brought to the boil, filtered hot solution. After the loss of their crystals filtered off, washed with cold alcohol and dried at 40°C. Output - 9.2, Tpl.- 96.6°C.

1. The tool, which represents the α-crystalline form of 9-phenyl-s-octahydrophenanthrene with antioxidant, detoxifying, immune-modulating, anti-atherogenic, antic is erotic, anabolic, gipolipidemiceski action and the corresponding structural formula

with a powder x-ray obtained on Cu-K a radiation source with parameters characteristic of reflection, expressed in degrees of diffraction angle 2θ: 6,0 12,0 15,0 17,0 19,0 20,0 21,5, 21,7, 20,9 25,0 27, 0 28, 0 29,0 37,0 and melting temperature 96,8°C.

2. A method of obtaining a crystalline form of substituted 9-R-SIMM-hydroselenoquinolinate consists in the fact that the corresponding 9-R-SIMM-hydrosilicate crystallized from malopolyarnoi or non-polar solvent.

3. The method according to claim 2, characterized in that monopolarly or non-polar solvent is chosen from the series: hexane, chloroform, isopropyl alcohol.


Same patents:

FIELD: chemistry.

SUBSTANCE: method for preparation of 2,4,6-triarylselenium pyrylium chlorozincates includes the interreaction of 1,3,5-aryl-substituted 1,5-diketones with hydrogen selenide obtained by dissolution of zinc selenide in the hydrogen chloride solution in diethyl ether. The reaction medium is obtained by reaction of phosphorus pentachloride with water in diethyl ether medium. The 2,4,6-triphenylselenium pyrylium chlorozincate, C23H17SeCl·0.5ZnCl2, 265-268°C, 57.5; 2,6-diphenyl-4-(n-methoxyphenyl)selenium pyrylium chlorozincate, C24H19SeO3Cl·0.5ZnCl2, 262-264°C, 60.5; 2,4,6-tri-(n-methoxyphenyl)selenium pyrylium chlorozincate C24H21SeO3Cl·0.5ZnCl2, 238-241°C, 71 are described.

EFFECT: avoiding of gaseous hydrogen selenide formation

1 cl, 3 ex

FIELD: chemical technology.

SUBSTANCE: invention relates to the improved method for preparing selenopyrilium salts by interaction of 1,5-diketones with hydrogen selenide that is prepared in dissolving zinc selenide in mixture of acetic acid, hydrogen bromide and diethyl ether. The reaction medium is prepared by addition of acetic acid bromoanhydride to mixture of diethyl ether and hydrogen bromide an aqueous solution. The following indices of compounds are given below as, name, empirical formula, melting point and the yield of the end product, %, respectively: 2,4,6-triphenylselenopyrilium bromozincate, C23H17SeZnBr3, 256-258°C, 75; 2,6-diphenyl-4-(p-methoxyphenyl)-selenopyrilium bromozincate, C24H19SeOZnBr3, 247-252°C, 71; 2,6-diphenyl-4-methylselenopyrilium bromozincate, C18H15SeZnBr3, 205-207°C, 68. All prepared salts have been converted to the corresponding perchlorates. Method provides excluding the use of gaseous hydrogen selenide.

EFFECT: improved preparing method.

2 cl, 3 ex

The invention relates to a method of producing selenopyran displaying biological activity, as well as to medicine, pharmacology, food and cosmetic industries, and can be used in the production of food additives and drugs, broad-spectrum

The invention relates to medicine, pharmacology and food industry and can be used in the production of food additives and to obtain drugs for the regulation of metabolism

FIELD: medicine.

SUBSTANCE: invention relates to medicine, particularly to cardiology, and concerns treatments of cardiovascular diseases that is ensured by introduction of a composition containing stem cells and undifferentiated precursors prepared of adipose tissue by separating mature adipocytes and connective tissue.

EFFECT: that ensures restoration of blood circulation in ischemic region.

28 cl, 7 ex, 12 dwg

FIELD: medicine.

SUBSTANCE: invention concerns medicine, namely application of sodium thiosulphate as a hypolipidemic and antiatherosclerotic agent for oral introduction to treat dislipoproteinemia and atherosclerosis.

EFFECT: there is disclosed hypolipidemic and antiatherosclerotic agent.

5 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medical products and concerns a pharmaceutical tablet, contains a therapeutically effective dose of crystalline telmisartan sodium salt of fusion temperature 245±5°C and diuretic hydrochlorothiaside, as well as one or more adjuvants used to prepare medical products. There is also disclosed method for making thereof. According to the invention, the pharmaceutical tablets are storage-stable.

EFFECT: intended for prevention or treatment of diseases wherein application of angiotensin II antagonists ensures the therapeutic effect.

23 cl, 7 tbl, 8 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine and can be used for treatment of neural diseases. The invention represents a combined antihypoxic medical product characterised by that it contains vinpocetine and succinic acid in the relation 1:2-50. Succinic acid potentiates antihypoxic action of vinpocetine.

EFFECT: invention provides extended range of medical products used for treating various ischemic conditions of central nervous system.

5 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine and pharmacology and presents a pharmaceutical composition based on alpha-lipoic acid as an aqueous solution for injections, for treatment and/or prevention of a disease chosen from group including alcoholic and/or diabetic polyneuropathy, coronary atherosclerosis, hyperlipidemia, hyperlipoproteinemia, mild and moderate viral hepatitis type A, hepatic cirrhosis, heavy metal salts poisoning, intoxications of various aetiologies, differing that it contains ethylenediamine, propylene glycol, solubiliser presented with plasdone, water for injection or 0.9% NaCI solution for injection in a certain relation components in the composition.

EFFECT: invention provides improved stability and absence of sediment in the solution, as well as extended range of products.

5 cl, 1 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: use of disodium salt of 4,4'-di(sulphophenyl) sulphone as a hypolipidemic and an antiatherosclerotic agent during treatment of dislipoproteinemia of atherogenic nature and atherosclerosis of various localisation is proposed. The proposed preparation reduces level of cholesterol and triglycerides in blood plasma (hypolipidemic action), reduces cholesterol content in the aorta and degree of its atherosclerotic damage (antiatherosclerotic action).

EFFECT: preparation exhibits low toxicity and efficiency during oral administration.

5 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to therapy, and concerns treatment of chronic arterial insufficiency. That is ensured by introduction of the preparation Antistax once a day in a dose 720 mg within 10 days, and then in a dose 320 mg within 20 days in addition to the conventional therapy involving antiaggregants, anticoagulants and vasodilators. Besides, Xymedone is introduced in a daily dose 1 g within 10 days in combination with machine pneumatic massage in mode "running wave" at duration of procedure 45 minutes and more and maximum pressure in chambers 100 mm Hg and less.

EFFECT: such complex of pharmacological aids introduced in developed doses and modes in combination with pneumatic massage provides effective treatment ensured by improved microcirculation and normalised lymphatic and venous blood flow.

3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, particularly to experimental cardiopharmacology and can be used for correction of endothelial dysfunction. It is ensured by simulation of endothelial dysfunction in experiment by intraperitoneal introduction to Wistar rats of N-nitro-L-arginine methyl ester dosed 25 mg/kg within 7 days. Thus the degree of dysfunction development is estimated by the relation of endothelium independent and endothelium dependent vasodilatation. Dysfunction is corrected by intraperitoneal introduction of preparation phosphogliv lyophilisate dosed 5.0 ml/kg and 0.5 ml/kg.

EFFECT: invention provides effective correction of endothelial dysfunction in specific experimental conditions.

2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to vascular surgery and intensive therapy, and can be used in treating the patients with acute limb ischemia. It is ensured by preoperative intravenous introduction of Perftoran during 12 hours in a dose 5 ml/kg of body weight combined with inhalation of 40-50% oxygen-enriched air mix in combination with introduction of preparations improving tissue microcirculation. It is followed with operative intervention that depending on the involvement level involves surgical approach to arteries wherein oxygenic Perftoran is introduced in amount 50 ml. Then arteries are clamped with main arteries and collaterals being excluded from blood circulation, and blood flow is restored. After the operation, during 12 h the patient takes inhalations of the oxygen-enriched air mix.

EFFECT: method allows improving clinical effectiveness of such patients, and also preventing development of postischemic syndrome due to joint introduction of oxygenic Perftoran and the oxygen-enriched air mix.

1 ex

FIELD: medicine.

SUBSTANCE: hop or hop-product is subjected to isomerisation reaction in presence of water in alkaline medium and at least one extraction, which is carried out by at least one organic solvent, selected from group of alcohols, water-containing alcohols, ketones, water-containing ketones or ethers or their mixtures or alkalised water. Reaction of isomerisation and at least one extraction is continued until obtained is extract which contains 8-prenylnaringenyl, in which (8-prenylnaringenin×100%)/(8-prenylnaringenin+6-prenylnaringenin) ratio constitutes at least 50%. By said method obtained is hop extract, which has estrogenic and anti-proliferative bioactivity. Hop extract is applied for producing medicament in which probable proliferative activity, caused by estrogenic activity of 8-prenylnaringenin, is inhibited or balanced by anti-proliferative activity of xanthogumol. Hop extract is applied for producing medicament for treatment or prevention of one of conditions, symptoms, complaints or diseases, caused by disturbance of hormonal balance of estrogenic nature.

EFFECT: invention allows realisation of said function.

25 cl, 2 tbl, 2 ex

FIELD: food industry.

SUBSTANCE: preparation for usage as feeding contains Bifidobacterium breve in quantity 1×104 -1×1010 cfu/g and a mixture of indigestible carbonhydrates. Carbohydrates are chosen from indigestible monosaccharides up to hexasaccharides of the same carbohydrate structure and from indigestible heptasaccharides and top polysaccharides of the same structure including inuline. Addition to children feeding and infant food containing mentioned preparation are proposed as its usage for healing or prevention of children immune disturbances as for usage for children obtaining artificial of partly breast-feeding.

EFFECT: usage of the preparation for producing of composition for prevention and healing of insufficient energy consumption, also for preparation of composition for inhibiting of eosinophils infiltration when having allergy.

16 cl, 7 tbl, 29 ex

FIELD: chemistry; biochemistry.

SUBSTANCE: invention relates to biotechnology and design of agents with immunomodulating properties. A new fungal strain Penicillium verrucosum VKPM F-984 and a new immunomodulating agent based on the strain are proposed. The strain is extracted from microflora of ginseng roots and is kept in a medium which contains mineral salts, glucose and asparagine. Fungus mycelium is extracted with a water-alcohol solution (70% ethanol solution). The advantage of this agent is its natural occurrence and effecient stimulation of adaptive capabilities of the body.

EFFECT: obtaining an extract which has stimulating action on cell and humoral immunity, improves immune status of the body.

3 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new derivatives of imidazo[1,2-c]pyrimidinyl acetic acid of formula (I) or to its salts: , where R1 is ,, in which n is an integer ranging from 0 to 6; Y is aryl, where the said aryl is optionally substituted at a substitutable position with one or more substitutes selected from a group which consists of halogen or C1-6alkyl, optionally substituted with mono-, di- or trihalogen; R2 is hydrogen; R3 is hydrogen or halogen; and R4 is hydrogen. The invention also relates to derivatives of imidazo[1,2-c]pyrimidinyl acetic acid of formula (I-i) or to its salts, to a drug, to use of compounds in paragraph 1, as well as to a drug in form of a standard single dosage.

EFFECT: obtaining new biologically active compounds, which are active towards CRTH2.

23 cl, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medical products and concerns an ellagic acid composition for immune system enhancement, differing that additionally is contains chitosan beta-1.3/1.6-glucans or oligosaccharides.

EFFECT: offered composition possesses enhanced immunostimulating effect.

3 ex

FIELD: medicine.

SUBSTANCE: invention refers to pharmacology and can be used in veterinary science and medicine for chemotherapy. There is disclosed immunostimulating and antioxidant lithium composition containing lithium ascorbate and lithium aspartate in percentage ratio 50:50.

EFFECT: expansion of the list of low-toxicity immunomodulators applicable for manufacture of drugs.

1 dwg, 2 tbl

FIELD: medicine.

SUBSTANCE: invention concerns medicine, particularly therapy, and can be applied in chronic disease treatment. Method involves causative agent extraction or determination of antibodies to causative agents or extraction of genetic components from blood, body fluid or smear. Treatment is performed by vaccine drugs specific to one or several identified causative agents, additionally immunomodulators are administered.

EFFECT: activated repair processes, arrested development of disease state of organs and systems due to elimination of identified pathogen from organism and to immune correction.

3 cl, 8 ex