Method of producing n-(beta-hydroxyethyl)4,6-dimethyldihydropyrimidone-2

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and a method of producing N-(β-hydroxyethyl)-4,6-dimethyldihydropyrimidone-2, known in medicine as Xymedon, involving recrystallisation of hydrochloride, N-(β-hydroxyethyl)-4,6-dimethyldihydropyrimidone-2 from ethanol and then treated with a sodium hydroxide solution in ethanol. The sodium chloride formed is removed by filtering. Crude N-(β-hydroxyethyl)-4,6-dimethyldihydropyrimidone-2 is separated by evaporating ethanol and purified by double recrystallisation from chemically pure isopropyl alcohol in the presence of aluminium oxide and activated carbon.

EFFECT: method enables to obtain a highly pure product.

3 ex


The invention relates to the field of chemistry and technology of heterocyclic compounds, pyrimidine series, namely N-(β-hydroxyethyl)-4,6-dimethylpyrimidine-2, which is called Ksimedon recommended for use in medicine as a burn-drug immune actions [Segizbayev, Gasimov, Mavergames, Usernick. Ksimedon in clinical practice, ed. NGMI, Nizhny Novgorod, 2001] and in veterinary medicine for the prevention and treatment of gastrointestinal diseases in calves [RF Patents №2086240 and No. 2179846].

A known method of producing Ximena [RF Patent №2044730] hydrochloride Ximena obtained by the interaction of ethanolgasoline with acetylacetone in the environment of isopropyl alcohol in the presence of concentrated hydrochloric acid by treating it with an alkaline reagent (sodium hydroxide, sodium carbonate, sodium bicarbonate, aqueous ammonia) in water or in aqueous chloroform to obtain a solution Ximena with the subsequent removal of water and the partial removal of the chloroform and planting of Ximena from a concentrated solution in chloroform with acetone.

The above method is adopted as the closest equivalent.

Validation of this method in the experimental conditions showed that the resulting ksimedon does not match in appearance pharmacopoeial article [the Fund 42-0037-4764-03, as the product has orange or even red color. To bring the product to the Pharmacopoeia purity had to miss the solution Ximena in chloroform to distillation parts of chloroform through a chromatographic column filled with alumina [Begaliev, Gahaysuddin, Sgharifov, Vpoloborota, Inc, Sielecki, Spodarev, Vpoly. "Himiko-pharmaceutical journal, volume 42, issue 4, p.43-45, 2008].

The disadvantages are the counterpart:

- the use of inefficient column chromatography;

- use of toxic substances, chloroform and ammonia;

- the inability to regenerate formed by the planting of Ximena mixture of chloroform and acetone, as their solutions are practically not separated by rectification.

The technical object of the present invention is to develop a method of producing Ximena devoid of the above disadvantages.

The technical result is achieved by the fact that pre-hydrochloride Ximena recrystallized from ethanol to remove impurities that cause coloration in the processing of alkaline reagents, purified hydrochloride Ximena treated with sodium hydroxide solution in ethanol medium, the precipitated sodium chloride is removed by filtration and the resulting solution Ximena in ethanol concentrate. Fallen ksimedon raw soda is containing up to 4% of sodium chloride, filtered and purified by double recrystallization from isopropyl alcohol brand "chemically pure" in the presence of aluminum oxide and activated carbon.

The developed method allows to obtain ksimedon with a purity of more than 99% (according to HPLC), satisfying the Fund.

Distinctive features of the proposed method are:

the exception is the use of column chromatography for the purification of Ximena;

- exclusion from toxic chemicals - ammonia, chloroform and mixtures thereof with acetone, processing which is virtually impossible with conventional methods, and burning it uneconomical and unsafe for the environment due to the formation of phosgene.

The method of producing Ximena is illustrated by the following examples.

Example 1. Crystallization of the hydrochloride Ximena.

Hydrochloride Ximena in the amount of 348 g dissolved under stirring at 80-90°C in a mixture of 300 ml of water and 1200 ml of ethanol. Then the resulting solution was yellow-brown color is cooled to 10-15°C and maintained at this temperature and stirring for 30-40 minutes the precipitation of the hydrochloride Ximena filtered off, washed on the funnel 100-140 ml) cooled to 10-15°C ethanol. Receive 250 g (71,8% of theory) of the pure hydrochloride Ximena white with a little white shade BL is Stasi crystals with TPL 240-241°C.

Example 2. Getting Ximena raw.

Sodium hydroxide (205,2 g, 5,13 moles) is dissolved with stirring and the temperature of 20-32°C in 3.0 liters of ethanol. To the resulting sodium hydroxide solution add 1.0 kg (4.8 moles) of recrystallized hydrochloride Ximena and stirred for 60 minutes Then the reaction mass was filtered to separate from the separated sodium chloride. The sodium chloride on the funnel was washed with 200 ml of ethanol. From the mother liquor is distilled 2.5...3.0 liters of ethanol, the residue is cooled to 10-15°C, kept at this temperature for ~30 min and filtered. Ksimedon raw washed over 300-500 ml of acetone and dried at ~80°C for 2-3 hours, get 735 g (73.5%) of Ximena raw with TPL 138°C with the content of the basic substance is 95.2%. The resulting ksimedon raw contains up to 4% of sodium chloride.

Example 3. Getting Pharmacopoeia Ximena.

Ksimedon raw (95,5 g) is dissolved at a temperature of 75...80°C 350...400 ml of isopropyl alcohol brand "chemically pure" with the addition of 50 g of aluminum oxide and 10 g of activated charcoal. Then a hot solution is filtered from aluminum oxide, activated carbon and sodium chloride. The precipitate on a vacuum funnel washed with 50 ml of hot isopropyl alcohol and combine the wash with isopropyl alcohol with the main filtrate containing ksimedon. The solution Ximena in isopropyl alcohol, cooled to 10-15°C and maintained at p and the temperature 30-40 minutes Fallen ksimedon filtered off, washed it over 100 ml of acetone and dried at 80°C for 3...4 hours. Get 69,78 g (73% per ksimedon raw) Ximena, appropriate for all indicators of the Fund, except for chloride (0,03 0,04...% instead of 0.02%).

The resulting ksimedon from the first crystallization repeatedly recrystallized from isopropyl alcohol with the aforementioned method. Get 49,54 g (71% per ksimedon from the first recrystallization) Ximena, appropriate for all indicators of the Fund 42-0037-4764-03.

The total yield of Ximena from two precrystallization is 51,83% of theory.

The method of obtaining N-(β-hydroxyethyl)-4,6-dimethylpyrimidine-2 by neutralizing its hydrochloride, characterized in that the hydrochloride of N-(β-hydroxyethyl)-4,6-dimethylpyrimidine-2 pre recrystallized from ethanol, then treated with sodium hydroxide solution in ethanol, to remove the formed sodium chloride by filtration, N-(β-hydroxyethyl)-4,6-dimethylpyrimidin-2 raw produce partial evaporation of ethanol and purified by double recrystallization from isopropyl alcohol brand "chemically pure" in the presence of aluminum oxide and activated carbon.


Same patents:

FIELD: medicine.

SUBSTANCE: invention refers to cosmetology, specifically to an agent for dyeing keratin-containing fibres, first of all, human hairs, containing at least one compound of formula (I) and/or its enamic form, with R meaning allylic group, hydroxyalkyl group with 2-6 carbon atoms, or if required, substituted benzyl group, X- meaning a physiologically acceptable anion, and at least one aldehyde.

EFFECT: invention allows producing dyeing with shine, improved washability and light resistance.

18 cl, 3 ex, 3 tbl

The invention relates to a new compound - derived 4-oxo-1,4-dihydropyrimidin formula I, having antihypoxic, cerebroprotective and immunotropic activity, and may find application in medicine

The invention relates to heterocyclic compounds having angiotensin II antagonistic activity

The invention relates to new biologically active compounds derived from 4-oxo-1,4-dihydropyrimidin having antiallergic activity, which can find application in pharmaceutical industry and medicine

-hydroxyethyl)-4,6 - dimethylpyrimidine-2" target="_blank">

The invention relates to chemistry and technology of heterocyclic compounds, pyrimidine series, namely 4,6-dimethyl-N-(-oxyethyl)-2-oxo-1,2-dihydropyrimidine, which is called ksimedon recommended for use in medicine as a burn-drug immune action [1]

A known method of producing Ximena [2] consisting in the conversion of the hydrochloride of 2-hydroxy-4,6-dimethylpyrimidine sodium salt of 2-hydroxy-4,6-dimethylpyrimidine, when heated, which ethylenchlorhydrine received ksimedon

The invention relates to an improved method of producing chlorinol containing o-hydroxyphenyl group, of General formula I-III I

< / BR>
where Ia 4-CL; 2-o-HOC6H6; R = 6-CH3< / BR>
IB 4-CL; 2-o-HOC6H4; R = 6-CF3< / BR>
IB 4-Cl; 2-o-HOC6H4; R = 6-C6H5< / BR>
Iك 4-Cl; 2-o-HOC6H4; R = 5-CN

Ia 4-Cl; 2-o-HOC6H4; R = 5-COOC2H5< / BR>
Ie 4-Cl; 2-o-HOC6H4; R = 5-C6H5< / BR>
If 4-Cl; 2-o-HOC6H4; R = H

Z 4-Cl; 6-o-HOC6H4; R = H

AI 2-Cl; 4-o-HOC6H4; R = H

IC 2-Cl; 4-o-HOC6H4; R = 6-C6H5< / BR>
IIa R = H

IIb R = 4' -OC3H7< / BR>
IIb R = 5' -Br

G R = 5' -NO2< / BR>
D R = 3' , 5' -Cl2< / BR>
IIIa R = H is used as intermediate products in the synthesis of universal stabilizers for polyethylene, i.e

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to oncology, and can be used in therapy of disseminated abdominal and pelvic cancer. The method involves the preoperative patient positioning on a mattress heated to temperature 37-39°C, the removal of primary and secondary cancer foci, the installation of drainage tubes in the abdominal and pelvic cavities. Thereafter, a reservoir is created to be filled with a perfusion solution specified from dialysis solution, Ringer's solution or 5% glucose and containing Oxaliplatin in dosage 50-130 mg/m2 or Mitomycin C in dosage 20 mg/m2 and 5-fluorouracil in dosage 1 g/m2. The stage of the initiation and during hyperthermic chemotherapy involves the forced cooling of the patient's occiput and cervical great vessels. For the hyperthermic chemotherapy, the perfusion solution of temperature 43-48°C is used, and for the postoperative chemotherapy, the chemotherapeutic solution of temperature 37-38°C is introduced through the kept drainages.

EFFECT: method allows to prevent tumour cell penetration into the vascular and lymphatic bed due to combined high-temperature, sensitising and cytotoxic action of the high concentrated chemopreparations in tumour tissue.

31 cl, 11 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to hydrophilic pharmaceutical compositions for treatment of burn wounds. According to the first version of invention, pharmaceutical composition contains 1-β-oxyethyl)-4,6-dimethyl-1,2-dihydro-2-oxopyrimidine (xymedone) in amount of 1-10 wt %, chloramphenicol sodium succinate in amount of 0.1-5 wt % and gel base. According to the second version of invention, pharmaceutical composition contains xymedone in amount of 1-10 wt %, chloramphenicol sodium succinate in amount of 0.1-5 wt %, tri-(oxymethyl)-aminomethane (trisamine) in amount of 0.5-1.5 wt %, anesthesin in amount of 0-1 wt % and gel base.

EFFECT: compositions of invention are efficient for treatment of infected burn wounds, possess reparative, anti-inflammatory and antimicrobial effect as a result of synergetic and prolonged effect of xymedone and chloramphenicol sodium succinate.

8 cl, 2 tbl, 10 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to oncology, and can be used within integrated treatment of locally advanced clay pipe cancer. That is ensured by blood sampling in the amount 200-250 ml from the median cubital vein, centrifugation and plasma separation in the amount 10 ml in 9 syringes of 20 ml. Plasma containers are placed in a freezing chamber, and the rest cell suspension is added with 150 ml of physiologic saline and reinfused intravenously drop-by-drop. On the following day, the lingual artery is catheterised to introduce a mixture incubated at temperature 37 C for 30 minutes and containing 10 ml of autoplasma and 30 mg of methotrexate in one syringe and 500 mg of 5-fluorouracil and 10 ml of autoplasma in the second syringe. Such mixture is introduced daily during 4 days. 3 weeks later, a surgical removal the tumour follows with a bed of the removed tumour being injected all around during the operation with the mixture of 30 mg methotrexate and 10 ml of autoplasma incubated similarly that is followed with operative wound closure.

EFFECT: method allows higher clinical effectiveness in the case patients that is ensured by chemopreparations depot in a tumour lesion.

1 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, oncology, and can be used for treating locally advanced breast cancer. For this purpose, the method starts with chemotherapy. 15-30 minutes later, it is followed with hyperthermia at temperature 41.0-42.0°C on the periphery of a tumour at exposure time 90-60 min, respectively. If observing involution of the tumour more than by 30% by RECIST criteria, radical mastectomy followed by radiation therapy is performed. A less evident involution requires preoperative radiation therapy followed by radical mastectomy.

EFFECT: method allows improving a local therapeutic effect due to the fact that on the periphery of the tumour, total vascular dilatation and blood flow increase are observed that allows for maximum penetration of medicinal agents into the tumour, and in the centre of the tumour, high temperature is generated because of decreased blood flow and therefore heat extraction thereupon by the end of the procedure in the tumour region, blood flow is slowed in vessels and stops almost, the cumulated medicinal agents are kept in the tumour for a long time that allow prolonging the cytotoxic action of chemopreparations on malignant cells.

3 cl, 6 dwg, 2 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to surgery and endocrinology, and can be used in the patients requiring a conservative treatment of acute pancreatitis. That is ensured by a standard medical therapy by the introduction of infusion preparations, anaesthetics, spasmolytics, vasoconstrictors, antibiotics, novocaine, cytostatics, omeprazole, sandostatin. For the period of treatment, hunger with voluminous drinking is prescribed. Pit of the stomach is cooled. In addition, procaine blocks in the round ligament of liver are applied that implements the introduction of at least 200 mg of Immunomax and 10 ml of 5-fluorouracil. During 2 days, at least 1.0 g of metronidazole, 0.1 g of furaginum, at least 15.0 g of Enterosgel are intaken. During the whole therapeutic course, at least 1 ml of Sporobacterine suspension together with cooled water is taken once a day. Starting from the sixth day and during the whole therapeutic course of hospital treatment, 1 tablet of Mezym forte 2 times a day is prescribed. For at least two weeks after discharge from the hospital, treatment in a locally available health resort is continued.

EFFECT: method allows reducing considerably the probability of acute pancreatitis transition into a destructive form due to the effect of specified therapy by various pathogenesis links of specified disease.

2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to gastroenterology, and deals with treatment of liver diseases of various geneses. For this purpose as hepatoprotective medication introduced are derivatives of bis(2-thio-4,6-dioxo-1,2,3,4,5,6-hexahydropyrimidin-5-yl)arylmethanes.

EFFECT: method ensures reduction of cytolysis manifestations under impact of damaging agents, reliable reduction of dysproteinemia, acceleration of recovery of liver detoxication processes, increase of endogenic alpha interferon induction and, as a result, increase of efficiency of liver cell protection in case of hepatitis of various geneses.

5 tbl

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, namely to oncology and can be used in combined treatment of cancer. Versions of pharmaceutical preparation according to the invention include 7-tret-butoxyiminomethylcamptothecin and other chemical therapeutic agent. The inventions also relate to application of 7-tert-butoxyiminomethylcamptothecin for obtaining medication for application in combination with one or several chemical therapeutic agents.

EFFECT: application of the inventions allows to increase anti-tumour effect due to enhancement of cytotoxic effect with respect to tumour cells due to synergetic action of components.

9 cl, 18 tbl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to an agent representing 5-amino-6-methyluracil of formulas (1) which exhibit antioxidant activity and to a method for preparing thereof. The agent can be used in medicine for preparing a drug capable to inhibit lipid peroxidation processes and to activate restorative processes in chemical intoxications. The method for preparing 5-amino-6-methyluracil consists in hydrasine sulphate reduction of 5-nitro-6-methyluracil in ethanol medium at temperature 70-80°C with Raney-nickel added as a catalyst followed with product recovery.

EFFECT: invention allows for higher product yield.

2 cl, 5 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, oncology, and can be used for treating rectal cancer. That is ensured by daily 5-fluorouracil chemotherapy for 5 days combined with the following introduction of a platinum preparation. It is followed with gamma therapy according to the dynamic dose fractionation with the amplified fractions of 4 Gy for the first 3 days. Further, said ray therapy is ensured by small fractions in the superfractionation mode, twice a day, every 4-5 hours, of 1.25 Gy to total basic dose of 47.0 Gy. In addition, every night at bedtime, Derinat gel is introduced in microenemas of 5-10 ml for the first 5 days of treatment, of 10-20 ml in amplified fraction radiation, of 30-35 ml in small fraction radiation, of 25-30 ml after the termination of the radiation course for 2 weeks.

EFFECT: method provides increasing TBD to 47,0 Gy that is an equivalent of 50 Gy of conventional radiation dose fractionation, as normal tissues allow delivering the specified dose without the evident ray-induced reactions.

2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to oncology and may be used in treatment of cervical cancer. The method includes chemotherapy with 5-fluorouracil for 5 days every day, followed by simultaneous administering of platinum drugs and radiotherapy according to the scheme of dynamic dose fractionation with extended fractions of 4 Gy to the pelvis during the first 3 days. Then radiation therapy is continued in small fractions of 2.5 Gy once a day up to a total focal dose of 50 Gy, with additionally administered derinat-gel once a day to vaginal tube and simultaneously in the form of microclysters into rectum in scope of 10-15 ml during the first 5 days of treatment. Then for 3-4 hours prior of or 1-2 hours after each session of radiation and after radiation therapy course termination the installations into vaginal tube in the same extent are continued for 2-3 weeks.

EFFECT: method enables to increase resorption of tumor due to increasing the total focal dose up to 50,0 Gy with a decrease in the number and expressivity of radiation reactions due to restoration of oxidative-antioxidant processes and reduce the concentration of free radicals in tissues under influence of derinat gel.

2 ex

FIELD: medicine, oncology.

SUBSTANCE: invention relates to a method for treatment of uterus body topically spread cancer involving applying chemotherapy and intrauterus irradiation. Method is carried out by the following manner: at the 1-st day of treatment cyclophosphan is administrated in the dose 1200-1600 mg by interstitial paratumoral route; at the 2-d day cream-like based fluorouracil in the dose 300-550 mg or adriablastin in the dose 20-30 mg is administrated into uterus cavity; on the next day sйance of intracavitary irradiation is carried out in the dose 10 Gr. All these procedures are repeated three times with interval for 6 days. Method provides high topical concentrations of chemopreparations in tumor zone in reducing their adverse toxic effect that results to the curative effect of patients of elderly age with accompanying therapeutic diseases.

EFFECT: improved method for treatment.

1 ex

FIELD: medicine.

SUBSTANCE: method involves applying eradicative anti-helicobacterial therapy comprising Omeprazol administration at a dose of 20 mg twice a day and Ximedone at a dose of 500 mg twice a day in 12 days long course.

EFFECT: enhanced effectiveness of eradication; reduced adverse side effects risk.