Balneological agent glinofir for treating and preventing various diseases

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to balneology. A balneological agent for treating and preventing various diseases is prepared by the gradual and sequential mixing at room temperature of yellow clay, natural brine of Bolshoy Tambukan Lake, sage essence, dimethyl sulphoxide in certain relations.

EFFECT: agent possesses the more prominent therapeutic effect.

5 tbl, 2 ex

 

The invention relates to medicine, namely to Spa therapy for the treatment and prevention of various diseases.

Famous balneological facilities for treatment of various diseases, for example: mud silt sulfide mineral, mud, organic peat and sapropel (Oliferenko Century So / In kN.: Vodoteplolichil. - M., 1986). The disadvantages of mud is often qualitative environmental non-compliance with sanitary norms and specific contraindications to the appointment of patients.

The closest in technical essence to the present invention is previously patented balneotherapy for treatment and prevention of diseases, for example, "Linefit". Specified in balneotherapy consists of natural components: bischofite is 2.5-3.5 ml, water - 41,5-42,5, essential oils of fir - 1-2 ml, white clay - 55-52 g and silver water. Rheological parameters: the shear - 2071, stickiness - 4137 often meet the requirements of MU 2000/36 - conforming (normal rheological parameters 1500-2500 Dyne/cm2for volcanic mud. The concentration of bischofite equal to 1.35 g is similar to the local baths (patent No. 2329815).

"Linefit" has the following disadvantages:

The tool has the same contraindications, and therapeutic mud, and especially not always differentiated impacts who meet certain pathological disorders in humans.

The technical result of the proposed balneological means "Glenfir is more effective and potent with higher therapeutic effect of finely dispersed, homogeneous and elastic substrate with enhanced therapeutic indications and targeted differential impact on certain types of disease.

For this yellow clay - 1000±10 g mixed in the following ratio: with brine (cheaper natural component) from Big lake Tambukan - 350-450 ml, essential oil of sage - 1-2 ml) and dimethylsulfoxide 98±2 ml Due to proper ratios of ingredients rheological parameters "Glenfir": shear - 2126, stickiness - 5152 correspond conforming to the requirements according to Annex No. 12 to the Regulation on the establishment of therapeutic properties and qualities of natural objects (mineral waters and therapeutic muds), to the order of the Ministry of health and social development of the Russian Federation (the norm of rheological parameters 1500-2500 Dyne/cm2for volcanic mud. The concentration of the brine is 15±5 g/DM3- similar to the local baths).

Thus, balneotherapy "Glenfir" is conditioned by the requirements for the rheological parameters to the volcanic mud, for the future is the sing it as a therapeutic and preventive tool.

At the present time, given therapeutic properties of yellow clay, essential oils of sage, dimethyl sulfoxide and brine from the Great lakes of Tambukan, as well as sanitary-bacteriological welfare received Glinoer, you can enable its therapeutic application in the form of applications for specific areas of the body: lower back, neck, joints after heating on a water bath.

Trace element composition of the powdered air-dried powder of yellow clay and brine are presented in table 1.

Table 1
Trace elements in samples of yellow clay and brine from the Great lakes of Tambukan
NN p/pIndicatorsAverage spread-
of microelement
Ltd, in % of dry. prophetic in the earth's crust (Clarke)
Yellow clay is investigated by atomic emission spectrophotomet
re Optima 2100" company Perkin-Elmer, % on dry clay
Brine from the Great lakes of Tambukan investigated on the same spectrophotometer, % brine
12345
2 Samples,%, (dried at 105°C)Humidity native sample to 2.57The dry residue in the brine 2,294
3Titanium0,45not ODA.not ODA.
4Manganese0,0350,0100,0000129
5Vanadium0,010,002<0,00000005
6Copper0,00470,0040<0,00000003
7Nickel0,00580,0035<0,00000004
8Zinc0,00830,00280,0000026
9Chrome0,00830,0025&l; 0,00000007
10Tin0,00025not ODA.not ODA.
11Lead0,00110,0010<0,000001
12Cobalt0,0018not ODA.not ODA.
13Cadmium0,0000130,000012<0.00000005
14Molybdenum0,00011not ODA.not ODA.
15Li0,000500,000100,00012
16Barely0,00030not ODA.not ODA.
17Barium0,0580,085 <0.000005
18Strontium0,0030,00520,00041
19Iron1,0<0,00001

As follows from table 1, the microelement composition of the investigated natural substrates generally does not exceed the average prevalence of trace elements in the earth's crust. Naturally, the majority of trace elements entering into the composition of the clay in the form of a water-insoluble complexes that are not detected in the brine. However, it should be noted that the brine is not detected a number of trace elements in the clay, minor deviations may not have a significant impact on therapeutic and preventive properties of these substrates when applied externally. Differences in the treatment effect more may be due to their makrogiannis composition, for example, a significant amount of cation magnesium and sodium in the brine. As microelement composition in all substrates does not exceed the average prevalence in the earth's crust, so they can widely be used in therapeutic and preventive purposes in a mixture with clay, complementing each other in diverse quality microlam ntdom composition.

Physico-chemical composition of the brine used to obtain balneological means presented in table 2.

Table 2
Physico-chemical composition of the brine from the Great lakes of Tambukan used to obtain "Glenfir"
Physico-chemical composition of the brine used to obtain balneological means "Glenfir"Brine from the Great lakes of Tambukan
Date of sampling23.03.2012 year
LocationStavropol region, the Piedmont region
pH7,6
In 1 l of water cations-anions:gmg·equivalent.% mg·equivalent.
Ammonium (NH4)Not OBN.
Potassium (K)0,05201,3300,39
Sodium (Na)4,2892186,48755,46
Magnesium (Mg)1,5176124,80737,12
Calcium (Ca)0,472023,5537,03
Iron (Fe)≤0,0001
Amount6,3363336,117100,00
Fluorine (F)Not ODA.
Chlorine (Cl)4,0116113,12733,64
Bromine (Br)Not ODA
Iodine (J)Not ODA.
Sulfate (SO4)10,6332221,38365,84
Bicarbonate0,07851,2870,38
Carbonates (CO3)0,01140,3800,14
Amount14,7347336,117100,00
Silicic acidNot ODA.
Boric acidNot ODA.
Mineralization
The dry residue22,940
Radium (Ra), Bq/kg1,68±2,80
Uranium (U), g/l225,0*10-7
Cesium (CS137), Bq/kg1,28±1,55
Thorium Th-232, Bq/kg1,35±3,06
Potassium-40, Bq/kg6,63±23,49
The density D (g/cm31,02
Formula Kurlov

Physico-chemical composition of the lake brine presented in table 2 refers to the saline solution, it was investigated major cations and anions. Their composition is characterized as a sodium-sulfate [Cl - 34 mg-equiv.% SO4 -66 mg-equiv.%] magnesium-sodium [Mg - 37 mEq.%, (Na+K) - 56 mg-equiv.%)], slightly alkaline reaction medium (pH 7,6), salinity 21,0 g/DM3. The main anion, superior to other content, is the sulfate ion, the cation superior to others, is sodium. In this regard, when astrologicheskih diseases therapeutic effect is substantiated by the presence in its composition of sodium sulfate (Na2SO4·6H2O), essential oils of sage and dimethyl sulfoxide in therapeutically active concentrations.

Thus, we have obtained a new balneological substrate in a mixture of yellow clay, essential oil of sage and dimethyl sulfoxide. Brine for injection in balneological drug chosen to obtain balneological means conforming with the rheological parameters and the necessary curative effect.

Physico-chemical composition and sanitary and bacteriological state of new balneological means "Glenfir":

Designation standard (TU)
Name of raw materials
Clay treatmentTHE 9310-002-00288024-99
BrineTHE 9154-001-93934149-08
The sage oil natural purifiedTHE 9156-001-77344782-2007 or GF 419-46
TimerswitchFS 42-2980-91
Laminated packages Doy - Paek""RUSK LINE Ltd in Moscow

The resulting preparation was investigated in balneotherapy. Balneological evaluation of the obtained preparation was made in terms of physico-chemical and sanitary-microbiological status. To address the question about the use of the submitted sample Glenfir" for therapeutic purposes based on the Department of resort resources of the fgbi "Pjatigorskogo state research Institute of balneology of the FMBA of Russia" and Pyatigorsk centre for sanitary and epidemiological supervision performed the following study.

The external characteristics of the obtained sample Glenfir": yellow color, with a smell of sage oil, and dimexide, the consistency of thick cream, homogeneous structure, without visible inclusions.

Humidity sample "Glenfir" 36,69%. The results of physico-helices the second part of "Glenfir are presented in table 3.

Evaluation of a new balneological funds were made in accordance with the requirements of Annex 12 to the Regulation on the establishment of therapeutic properties and qualities of natural objects (mineral waters and therapeutic muds), to the order of the Ministry of health and social development of the Russian Federation.

Table 3
Physico-chemical indicators in the Spa means "Glenfir" received 12.05.2012 year
NN p/pIndicatorsDimensionThe norm for mudThe results of the analyses sample preparation
1Date received medication12.05.2012
2Humidity%40-8036,69
3Volumetric weightg/cm31,1-2,01,705
4ShearDyne/cm21500-25002126
5StickinessDyne/cm25152
6Solids larger than 5 mm%NoNo
7The same size of 0.25-5.0 mm%No more than 32,86
8The same size of 0.1-0.25 mm%5,46
9Heat capacitycal/g·deg0,4-0,60,58
10Ash% dry. prophetic-inOver 9091,58
11The reaction medium pH7,0-9,07,39
12Redox potential (Eh)MV-500...+500+105
13The sulfide total% of eats. prophetic-VA0,15-0,50Not OBN.
14The iron sulfide“ “Not OBN.
15Iron (II) oxide“ “0,402
16Iron (III) oxide“ “3,100
17The organic carbon% abs. dry. clayLess than 101,02
18Nitrogen, organic% abs. dry. clay 5,69
19The C/N ratio0,18
20Lipids“ “NoNot OBN.
20.1including carotenoidsmg % dry.NoNot OBN.
21Humic acid% abs. dry. clayto 3.73
22Mineralization of centrifugate of "Glenfir"g/l1-3513,0
24Trace elements% of dry clay (Clark)
24.1Titanium0,45Not ODA.
24.2Manganese0,0350,02421
24.3Vanadium0,010,00098
24.4Copper0,00470,00108
24.5Nickel0,00580,00910
24.6Zinc0,00830,003681
24.7Chrome0,00830,001890
24.8Tin0,00025Not ODA.
24.9Lead0,00110,001521
2410Cobalt0,0018 0,000702
24.11Cadmium0,0000130,000014
24.12Molybdenum0,00011Not ODA.
24.13LiA.0,000500,000708
24.14Berylliumtt0,00030not ODA.
at 24.15Barium0,0580,01332
24.16Strontiumit,0,0030,01593

Physico-chemical parameters in balneotherapy "Glenfir" refers to low-mineralized (13,0 g/l), bisulfide substrates, slightly alkaline reaction medium (pH 7,39). In "Glenfir" the content of hydrogen sulfide is completely absent. Humidity in Glenfir" 36,69%. It is close to the lower value requirements, pragya is up to therapeutic volcanic mud (40-75% for volcanic mud). Thus, the sample Glenfir" in its composition and properties are similar to therapeutic mud hills Akhtali (Akhtala resort Georgian Republic). In the list of the main types of mud CIS for peloids Akhtali field has the following limits of fluctuations of physico-chemical parameters: salinity mud mortar ≥1 g/l, the concentration of hydrogen sulfide of less than 0,010% on natural dirt, ash content of more than 95% on a dry dirt, pH 7.0, and 9.0, the redox potential of -50 to+200 MV, humidity 40-75%,a specific heat of 0.4-0.6 cal/g·deg weight and dimensions 1.3 to 1.7 g/DM3.Volumetric weight in Glenfir" 1.70 g/DM3that corresponds to the norm (1.3 to 1.7 g/DM3). The resistance value of the shift in the pattern of drug - 2126 Dyne/cm2meets the requirements of volcanic mud, prepared by the procedures (1500-2500 Dyne/cm2), i.e., approaching its average value.

The heat capacity of the drug is calculated by the amount of humidity in Glenfir" she 0.49 cal/g·deg.

The total amount of the drug particles larger than 5 mm is missing. The debris particles larger than 0.25 mm - 2,86%, which meets established standards (not more than 3%).

The investigated sample "Glenfir" contains the oxide of total ferrous iron 0,402% on air-dry the substrate. Trivalent W is spread contains 3.10% on air-dry the substrate, indicating that aerobic processes of its production. The redox potential (+105 MV) has a positive value that characterizes prepared procedures Glenfir" as the substrate, in which the oxidizing processes.

Microelement composition comprises manganese, vanadium, chromium, Nickel, copper, lead, and other elements (see table 3). Most of their contents does not exceed the average distribution of chemical elements in the earth's crust (3).

The content of organic carbon (Corg. "Pinophyta" - 1,02% on absolutely dry product), which is typical for substrates such as mud (not less than 0.1% of natural substances).

The content of biologically active lipids and carotenoids in the product was not found. The content of humic acids in Glenfir" to 3.73% on absolutely dry substrate, which indicates the biological activity of yellow clay used for its manufacture. UV absorption spectra of aqueous solutions of humic acids from Glinoer are characterized by the presence of absorption bands in the region of 260 nm and then a monotonic decrease in optical density.

Offer balneotherapy "Glenfir" is illustrated by the following examples:

Example 1. Suspension of clay about 1 kg to obtain "Glenfir" was subjected to sanitary is the processing of aplicom and then after removing it, and drop large particles of rock and sand was treated with brine from the Great lakes of Tambukan. Clay with brine defended, brine was decentralise and mixed fraction was poured into 1 l plastic vessels. After settling and desantirovaniya of these vessels brine to obtain balneological means "Glenfir" in the resulting mixture were added dimethyl sulfoxide and essential oil of sage. After mixing yellow clay with brine both substrate became viscous mass consistency of thick cream, homogeneous structure, without visible inclusions. In the mixture by syringe under pressure gradually with careful stirring introduce 1-2 ml of essential oil of sage and 98±2 ml of dimethylsulfoxide.

Example 2. About 1000±10 g yellow clay is placed in a 5-liter plastic vessel and mix it with 4 l of water, after settling, the water part is drained, but moist clay is poured in 1 l of brine and thoroughly mixing a suspension of clay with brine transferred to another 5-liter plastic vessel, simultaneously drop large particles of rock and sand, after settling brine decanted not completely, and a mixed fraction with clay and with brine transferred into a 1-liter plastic vessel, periodically decanter brine and adding a suspension of clay with brine. Then in the resulting mixture by syringe under pressure gradually with careful paramasivan and introduce 1-2 ml of essential oil of sage and 98±2 ml of dimethylsulfoxide.

The presence in Glenfir" biologically active agents: water, essential oils of sage and dimethylsulfoxide characterized by its high medicinal properties.

The composition of centrifugate obtained from sample Glenfir": chloride - sodium (mEq. %: Cl - 75, (Na+K) - 77), the pH is slightly alkaline (pH 7.8), mineralization of centrifugate 13,0 g/l in Glenfir" (see table 4).

The formula of the chemical composition of centrifugate has the following form:

Table 4
The composition of centrifugate of "Glenfir"
1 DM3solution containing cations and anions:gmg/EQ.mg/EQ. %
Sodium (Na)3,8726166,85377,11
Calcium (Ca)0,15277,6203,52
Magnesium (Mg)0,509541,90119,37
Amount4,348 216,374100,00
Chlorine (Cl)5,7839163,10475,39
Sulfate (SO4)1,909539,75418,37
Bicarbonate (HCO3)0,60479,9114,58
Carbonate (CO3)0,10813,6031,66
Hydrogen phosphate (HPO4)not ODA.
Nitrite (NO2)not ODA.
Nitrate (NO3)not ODA.
Amount8,4061216,374100,00
Boric acid (HBO2), g/DM3not ODA.is the
Silicic acid
(H2SiO3), g/DM3
not ODA.
Total mineralization, g/DM312,9409
The dry residue, g/DM315,07
pH7,80
Eh, mV+140
Formula Kurlov

Thus, the sample obtained "Glenfir", is determined by the mineralization of centrifugate - 13,0 g/DM3and the lack of pollution by particles larger than 5 mm, the microelement composition it does not exceed the average spread them in the earth's crust, so "Clinovir can be widely used for balneological procedures.

Sanitary and bacteriological state Glenfir" presented in tubize 5 and is within the normal range (table.5)

Table 5
Sanitary and bacteriological indicators "Glenfir"
№№ p/pIndicators"Glenfir"
1E-coli>10
2Title perfringens>10
3Title coccal flora>1
4Title Pseudomonas aeruginosa>10
5QMAFAnM CFU in 1 g mud35
6BGK (coli-forms)Not OBN.
7St. AureusNot OBN.
8Pathogenic m/FL., including SalmonellaNot OBN.
9Ps. AeruginosaNot OBN.
10Mould CFU in 1 gNot OBN.
11YeastNot OBN.

Pathogenic microorganisms were not detected. The number of mesophilic aerobic and facultative anaerobic microorganisms does not exceed allowable values. The drug can be used without the prior bacterial purification by bactericides show essential oil of sage and dimethyl sulfoxide.

Thus, the proposed balneotherapy "Glenfir", obtained by mixing yellow clay from Novo-Pyatigorsk career Stavropol region Piedmont region with brine from the Great lakes of Tambukan, essential oil of sage and dimethylsulfoxide, meets established standards by rheological parameters (shear strength and stickiness) and, therefore, can be used for procedures in the form of applications, as long as they meet air-condi-tion requirements for volcanic mud (1500-2500 Dyne/cm2in this regard, it can be used in therapeutic and prophylactic purposes, in accordance with medical indications and contraindications.

Physico-chemical parameters investigated drug belongs to low-mineralized (13,0 g/l), bisulfide, vysokopol the major substrates, slightly alkaline reaction medium, approaching in composition and properties to therapeutic volcanic mud Akhtali field Georgian Republic.

Offer balneotherapy "Glenfir" do not contain harmful substances and heavy metals in quantities exceeding maximum concentration limit for natural substrates, and therefore can be used in the form of applications due to sanitary-bacteriological well-being.

The proposed sample after inclusion in the composition of the brine, essential oils of sage and dimethyl sulfoxide is recommended to use in the form of a preformed balneological tools for therapeutic and preventive purposes.

The composition of this balneological tools selected for further production, this requires the development of technical specifications (TS) for this treatment-and-prophylactic substrate, the instruction on the packaging and instructions for use.

Some therapeutic indications of the "Glenfir":

1. Chronic diseases of the musculoskeletal system:

- non-infectious polyarthritis (rheumatoid) in remission or decaying exacerbation, without significant restriction of function of joints;

- dystrophic diseases of joints metabolic-endocrine and other etiologies;

- degenerative sousta is s - arthrosis, arthritis of various localization;

- atrophie infectious poly - and mono after suffering dysentery, brucellosis, gonorrhea, influenza, and other infections;

- diseases of bones, muscles, ligaments of the joints, trauma and fractures - osteitis, periostitis, osteomyelitis different stages (sequestration);

- spinal diseases: spondylitis (except tuberculosis), spondyloarthropathies, ankylosing spondylitis 1-2 tbsp., spondylosis different localization (better in the initial stage), the residual effects of injuries and wounds.

2. Chronic diseases of the peripheral nervous system:

- polyneuritis, plexitis, neuritis toxico-infectious, allergic and other etiology; neuromyositis, plexalgia, neuralgia, Radiologie metabolic, traumatic, colds etiology, lumbago;

- professional diseases of the peripheral nerve trunks on the ground of chronic intoxications (chemical industries, in agriculture, in case of poisoning with heavy metals), injuries.

3. Chronic diseases of the Central nervous system:

residual effects after suffering polio and other neurotropic infections in the absence of an active process, and sufficient motor function;

- vibration disease of different origin and localization.

4. Diseases of the peripheral is practical blood vessels:

- endarteritis sclerosis, spastic and mixed forms without significant pain syndrome and advanced trophic changes of the tissues (necrosis). In these cases, mud applications are assigned only on segmental type (lumbosacral region) and lower temperature (37-38°C);

- postthrombotic syndrome, with no tendency to relapse and migration process;

- varicose veins of lower extremities with slight edema; not far advanced lymphostasis (elephantiasis of the legs).

5. Chronic diseases of the digestive organs:

- chronic diseases of the stomach, flowing with high acidity, secretion and the presence of musculoskeletal disorders (Hypo-hyperkinesia stomach, hypertension stomach, pilorospazm, pain gastritis);

- chronic gastroduodenal ulcer in remission, with no tendency to bleeding in the near history and presence of decompensated pyloric stenosis;

- diseases of the operated stomach: a syndrome resulting intestine, small stomach; dumping syndrome, adhesive disease of the abdominal cavity;

- scar-ulcerative duodenitis, duodenostasis and others;

- chronic liver disease and biliary tract inflammatory, toxic-allergic nature, chronic hepatitis of different etiology without expressed W is lluhi and the process activity; Botkin's disease no earlier than 6 months after the icteric period (mud application on the liver area and the back is at a temperature 40-38°C);

- chronic cholecystitis, cholangitis, angiocholitis various etiologies being calm, adhesive disease after surgery. Cholelithiasis with rare and mild attacks of colic mud contraindicated!!!

functional diseases of the gallbladder and biliary tract

- various dyskinesia Hypo - and hypermotor type, hypotension congestive gallbladder;

- a chronic disease of the large intestine of various etiologies

- infectious, allergic, toxic-chemical and professional (poisoning with heavy metals), proceeding as spastic-flaccid psoriasis inflammatory and functional nature; proctitis, proctosigmoiditis, congenital abnormalities of the large intestine.

6. Chronic diseases and metabolic disorders:

- gout and gout (uric acid diathesis with deformation of the small joints of the hands and feet, with limitation of function;

- obesity all degrees combined with diseases of the joints, spine and organs of digestion, with preservation of the functions of the cardiovascular system, without the presence of hypertension;

- metabolic diseases of the peripheral nerve trunk of the century

7. Chronic diseases of the skin:

- psoriasis (summer form) limited localization, without exacerbation (in combination with heliotherapy), dry eczema, dermatitis and other

8. Chronic diseases of female genital organs inflammatory and functional character:

- residual effects and consequences of inflammation of the uterus and its appendages, without exacerbation;

functional disorders of the menstrual-ovarian cycle; primary and secondary infertility;

- adhesive disease, pelvic inflammatory and posleoperatsionnogo origin, without exacerbation.

Deployed contraindications for treatment Glenfir":

1. All acute febrile illness.

2. Tuberculosis and malignant lesions of the joints, bones and spine.

3. Diseases of the lungs and other internal organs tuberculosis and malignant etiologies (stomach, intestine, liver and biliary tract, pancreas, kidney and urinary tract, the female reproductive organs).

4. Tumors of the same organs benign course.

5. Disease of the blood forming organs, and blood.

6. Gastroduodenal ulcer disease with a tendency to frequent bleeding disorder and severe stenosis of the pylorus.

7. Chronic chimicheski (acid-free) gastritis with the decline of the power and anemia.

8. The HRO is practical pancreatitis of any clinical manifestations.

9. The collapse of the stomach and intestines.

10. Cirrhotic changes in the liver.

11. Gallstones and kidney stones, even flowing without frequent attacks.

12. Diabetes mellitus (initial presentation).

13. Thyrotoxicosis in any stage.

14. Pregnancy in all periods of development.

15. Disease of the heart muscle and valve apparatus with blood circulation above 1 tbsp. (limited applications).

16. Violation of cardiac rhythm (arrhythmia) any clinical manifestations.

17. Hypertensive heart disease or predisposition to hypertension.

18. Coronary heart disease with angina voltage and peace.

19. Myocardial infarction in the near history.

20. Disease of various etiologies (valid only segmental mud - appliques on the lumbosacral region).

Balneotherapy for treatment and prevention of various diseases, containing clay, characterized in that it is obtained by a gradual and consistent stirring at room temperature yellow clay, brine from Big lake Tambukan, essential oils of sage and dimethyl sulfoxide in the following ratio:

Yellow clay1000±10 g
Brine from the Great lakes is ambuen 350-450 ml
Essential oil of sage1-2 ml
The sulfoxide98±2 ml



 

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FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula IV, VIII-A and X, and to their pharmaceutical acceptable salts possessing the inhibitory activity on PI3-kinase (phosphoinositide-3-kinase). In compounds of formula IV and IX and Wd is specified in a group consisting of, , , and each of which can be substituted. In formula VIII-A, the group Wd represents the group or , wherein Ra is hydrogen, R11 is amino; in compound IV, Wa2 represents CR5; Wa3 represents CR6; Wa4 represents N or CR7; in compound IX, Wa1 and Wa2 independently represent CR5, N or NR4, and Wa4 independently represents CR7 or S, wherein no more than two neighbouring atoms in a ring represent atom or sulphur; Wb5 represents N; B represents a grouping of formula II, as well as in case of compound IV, B means C1-C10alkyl, C3-C10cycloalkyl, C3-C10heterocycloalkyl having one to six ring heteroatoms specified in N, O and S; in case of compound IX, B also means C1-C10alkyl, C3-C10cycloalkyl or 6-merous heterocycloalkyl having nitrogen atom; Wc represents C6-C10aryl or 5-18-merous heteroaryl having one or more ring heteroatoms specified in N, O and S, or phenyl or 6-merous heteroaryl respectively is equal to an integer of 0, 1, 2, 3 or 4; X is absent or represents -(CH(R9))z-, respectively; z is equal to 1; Y is absent. The other radical values are specified in the patent claim.

EFFECT: compounds can be used for treating such diseases, as cancer, bone disorders, an inflammatory or immune disease, diseases of the nervous system, metabolic disorders, respiratory diseases, thrombosis or cardiac diseases mediated by PI3-kinase.

68 cl, 11 dwg, 7 tbl, 55 ex

FIELD: medicine.

SUBSTANCE: composition 16-21ml consisting of a mixture of therapeutic preparations: Dona glucosamine sulphate 3.0 ml; ChondroGuard, or Mucosatum, or Chondrolon chondroitin sulphate - 2.0 ml; Alflutop 2.0 ml; Actovegin 4.0-5.0 ml; glucocorticosteroids Depo-Medrol 1.0-2.0 ml in the concentration of 40 mg/ml, or Diprospane 1.0-2.0 ml in the concentration of 7 mg/ml, or Metipred 1.0-2.0 ml in the concentration of 62.5 mg/ml; vitamins B1, B6, B12 Combilipen 2.0 ml, or Milgamma 2.0 ml, or Neurobion 3.0 ml; 95% or 70% ethanol 2.0-4.0 ml, is administered into a pathologically changed region. That is immediately followed by exposing the pathologically changed region and adjoining segments to a session of A shock-wave therapy in the following mode: pressure 1.2 - 4.0 bar, frequency 7-12 Hz, beat quantity 8000-14000 for 20-40 minutes. The complex procedures are performed within the course of 1-6 times every 7-10 days.

EFFECT: method enables the direct exposure on the pathologically changed region to achieve the optimum concentration of drug preparations therein with avoiding systemic prescription and preventing a risk of side effects.

3 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of general formula [1] or their pharmaceutically acceptable salts, which possess properties of an inhibitor of the JAK2 thyrokinase activity. In general formula radicals are selected from group (I) or (II). In group (I) X represents CH or N; R1 represents a halogen atom and R2 represents H, a halogen atom, CN, or is selected from the groups of formulas

,

or a group -ORP or 5-6-membered heteroaryl, containing 1-4 nitrogen atoms and optionally additionally containing an oxygen or sulphur atom or containing an oxygen atom as a heteroatom, optionally substituted; or (II) X represents -CRA; and RA represents a group of formula , RB represents (a) amino, optionally substituted with one or two groups, selected from the group, consisting of C1-6alkyl, C3-6cycloalkyl, (C3-6cycloalkyl)C1-6alkyl and C1-3alcoxyC1-3alkyl, (b) C1-3alcoxy, (c) hydroxy or (d) a 5-6-membered saturated cyclic amino group, which additionally can contain a heteroatom, selected from an oxygen atom; R1 represents a halogen atom and R2 represents H; R3 -R5 have values given above. Other values of the radicals are given in the invention formula.

EFFECT: compounds can be applied for the prevention or treatment of cancer, for instance hematologic cancer disease or a solid form of cancer, inflammatory disorder, for instance, rheumatoid arthritis, inflammatory intestinal disease, osteoporosis or multiple sclerosis and angiopathy, for instance, pulmonary hypertension, arteriosclerosis, aneurism or varicose veins.

14 cl, 19 tbl, 234 ex

FIELD: veterinary medicine.

SUBSTANCE: method of treatment of intervertebral disk disease in dogs comprises intravenous injection of 3-5.5% aqueous solution of lithium chloride based on 2.5-3.5 mmol/kg of animal body weight, and additionally subcutaneously 10-30% aqueous solution of polyethylene glycol-4000 based on 2-4 ml/kg of animal body weight every second day for 5-7 days.

EFFECT: increased efficiency and simplification of the method.

4 ex

FIELD: veterinary medicine.

SUBSTANCE: method of treatment of intervertebral disk disease in dogs comprises administering the medicinal product, and the medicinal product is used as 10-30% aqueous solution of polyethylene glycol-4000, which is administered subcutaneously in an amount of 2-4 ml/kg of animal body weight every second day for 5-7 days.

EFFECT: improvement of efficiency of the method.

1 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to a kit for targeted medical imaging and/or clinical medicine, and to a method for using the kit. The declared kit comprises a pre-guide probe and an effector probe, wherein the pre-guide probe comprises a primary guide fragment and a first bio-orthogonal reactive group, and wherein the effector probe comprises an effector element, such as a label or a pharmaceutically active compound, and a second bio-orthogonal reactive group. Any of the first and second bio-orthogonal reactive groups represents dienophile in the form of stressed 8-merous cycle (cyclooctene or cyclooctine), while diene represents electron-deficient tetrazine or other applicable diene. A method for using the kit involves administering the pre-guide probe into the individual and enabling the probe circulating in the individual system for a period of time effective to achieve binding of the primary guide fragment with the primary target with the unbounded substance discharge from the body, with the effector probe to be inserted.

EFFECT: invention involves using the [4+2] Diels-Alder retrochemical reaction with electron reuptake to bind the pre-guide probe and the effector probe that enables fast in vivo reaction behaviour.

12 cl, 12 dwg, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where X=S, SO or SO2, and one of radicals R1 and R2 is a hydrogen atom and the other has a value given in the claim, which are used for depigmentation of the skin and/or hair and/or body hair and for skin disinfection, to cosmetic application of the disclosed compounds, and to compounds of formula (I), wherein R1 and R2 can also be a hydrogen atom at the same time. The invention also relates to a cosmetic composition and a pharmaceutical composition based on the disclosed compounds and to methods of producing said compounds.

EFFECT: improved properties.

19 cl, 2 tbl, 30 ex

FIELD: medicine.

SUBSTANCE: method involves application of a dressing on the periodontal tissues. Before the application of the dressing, the periodontal tissues are irrigated with Dentos solution for more than once. The dressing is prepared by adding zinc oxide power and zinc sulphate to Dentos and mixing them to pasty consistency. The solid dental tissues are coated with the polymer film from the vestibular and oral surfaces to a cutting edge. The periodontal tissues and the solid dental tissues coated with the polymer film are coated with the dressing.

EFFECT: method provides the anti-inflammatory, hardening, haemostatic capillary-reinforcing, immunomodulatory and adaptogenic effects; it enables maintaining the active substance concentration in the periodontal tissues, removing the dressing from the solid dental tissues, preventing colouring them and providing the Dentos exposure on the restoration components.

2 ex

FIELD: medicine.

SUBSTANCE: treating locally advanced oropharyngeal cancer is ensured by a radiation therapy in the mode of dynamic dose fractionation. The radiation therapy is started by supplying a fraction dose of 2.4 Gy. After 2 days of treatment gap, the patient is exposed to total fractions at a fraction dose of 3.6Gy for three days. Each session is precede by placing high-structure hydrogel matrix of sodium alginate under a patient's tongue with metronidazole 150mg and bilberry 20-35mg pre-introduced into the matrix, for 4-5 hours twice every 1-2 hours. The two following sessions of the exposure at a fraction dose of 2.4 Gy are preceded by placing the matrix once under the tongue for 4-5 hours. After 2 days of treatment gap, the following 5 sessions of the radiation therapy are performed at a fraction dose of 2.4 Gy to a cumulative dose of 30Gy. Colegel-DNA-Ch high-structure disk is preliminary placed under the tongue for 4-5 hours.

EFFECT: method enables avoiding the compulsory gaps of the radiation therapy by reducing a rate of severe local radiation reactions, and provides the target delivery and accurate dosage of metronidazole administered into the patient's body leading to the partial death of well-oxygenated cells and re-oxygenation of hypoxic tumour cells.

2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine and cosmetology and can be used for the effective transdermal delivery of the wide range of active substances (AS). What is declared is a method for the transdermal delivery of the active substances as a part of PEG-12 dimethicone niosomes characterised by the fact that the AS are included into the niosomes in the concentration of 10% by homogenising gel containing 10% niosomes in the homogeniser APV.

EFFECT: invention provides the higher transdermal effect of the interstitial delivery of the AS as a part of the niosomes.

3 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: method of obtaining sanguinarine and chelerythrine sulphates includes extraction of milled overground part of macleaya microcarpa and/or macleaya cordata with water aliphatic alcohol, removal of water aliphatic alcohol in vacuum, alkalinisation of water distillation residue with hydrophobic solvent, processing organic phase with sulphuric acid, filtration, washing and drying of target product, with extraction of milled raw material being carried out with water aliphatic alcohol in presence of methanesulphoacid, and solution of alkaloid bases in hydrophobic organic solvent is additionally filtered through layer of hydrophobic solvent, and target product is subjected to boiling in acetone.

EFFECT: method makes it possible to increase quality of finished product, simplify technology of production of sanguinarine and chelerythrine sulphates, and reduce the process duration.

8 cl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to the pharmaceutical industry, namely to a composition possessing the analgesic and anti-inflammatory action (versions). A topical composition possessing the analgesic and anti-inflammatory action and containing chondroitin sulphate, phenyl trimethicone, stabilene 30, cetyl alcohol, cetyl palmitate, Carbopol, a wetting agent, triethanolamine, glucosamine hydrochloride, liposomes, beta-cyclodextrin, bitter orange flower oil, Lavandula angustifoiia oil, escin, betulin, hyaluronidase, ginger extract, harpagophytum extract, euxyl k727, demineralised water in certain proportions. The topical composition possessing the analgesic and anti-inflammatory action and containing chondroitin sulphate, phenyl trimethicone, stabilene 30, cetyl alcohol, cetyl palmitate, Carbopol, a wetting agent, triethanolamine, glucosamine hydrochloride, liposomes, beta-cyclodextrin, bitter orange flower oil, Lavandula angustifoiia oil, escin, betulin, hyaluronidase, ginger extract, harpagophytum extract, euxyl k727, demineralised water in certain proportions.

EFFECT: compositions possess the pronounced analgesic and anti-inflammatory effect; they are stable.

2 cl, 1 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to therapy, and concerns preventing and treating atherosclerosis. That is ensured by prescribing tablets or capsules with their active ingredients representing black elder blossom, marigold blossom and violet herb in certain proportions. Two tablets or two capsules are administered two times a day every 12 hours within the unlimited therapeutic course.

EFFECT: method provides the effective prevention and treatment of atherosclerosis, including reducing a thickness of carotid artery intima-medial thickness by suppressing the expression of anti-inflammatory cytokines and reducing blood serum atherogenicity.

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry, namely to a cholinergic agent. A mixture of bornyl acetate and camphene taken in a certain ratio possessing the cholinergic action.

EFFECT: above mixture possesses the pronounced cholinergic action.

3 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: method involves the exposure of biologically active points (BAPs), the intake of herbal teas, the conflict management and the compliance with sleep mode. The BAPs exposure is conducted by finger pressing and twisting. The exposure takes the first 10 days of the therapeutic course. The exposure length is 3-5 minutes and involves the finger pressing and clockwise twisting in the moderating rhythm. On the odd-numbered day, the exposure covers a group of points found on the meridians, including a posterior median one - one point, an anterior median one - two points, a spleen - a pancreas - one point, a stomach - one point, lungs - one point, a liver - one point, kidneys - one point, and an urinary bladder - one point. On the even-numbered day, the exposure covers a group of points found on the meridians, including a posterior median one - one point, an anterior median one - two points, a spleen - a pancreas - one point, lungs - one point, a liver - one point, kidneys - one point, and an urinary bladder - two points. The whole therapeutic course is of the length of 3.5-4.0 months; in the first two months, herbal tea of milfoil is taken, while in the second two months - herbal teas of centaury and St. John's wort. The therapeutic course is accompanied by complying with the general and water schedules.

EFFECT: method provides the higher clinical effectiveness ensured by avoiding the psychological rejection of the conducted treatment and creating the health memory in the children.

5 cl, 3 ex

FIELD: chemistry.

SUBSTANCE: application of 5% water solution of sodium and potassium salts of humic acids, obtained from leonardite brown coal, in dose 10.0 mg/kg as membrane-protective preparation.

EFFECT: application of composition described above makes it possible to extend arsenal of membrane-protective preparations from low-toxic, cheap, available natural raw material.

2 dwg, 2 ex

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