Method for treating diabetes mellitus patients for angiopathy by applying peloids

FIELD: medicine.

SUBSTANCE: method involves administering peloidotherapy as applications over lower extremities with sulfide mud temperature of 37-38°C during 10-15 min in 10 procedures long course alternating with carbonic-acid/hydrogen-sulfide water baths taken at 36°C during 10-15 min. The total treatment course is 10 procedures long.

EFFECT: reduced glycemia profile level; reduced lipid metabolism indices; improved regional blood circulation.

9 tbl

 

The invention relates to medicine, namely to the treatment of patients with diabetes mellitus type 1 and 2, is complicated by angiopathies of the lower limbs, using mud applications in combination with balneophtotherapy.

As the prototype used the results of the study pelotherapy on a similar group of patients ("the Effect of the combined treatment in the resort Essentuki on the state of regional blood flow in patients with diabetic angiopathy of the lower extremities" Diss. the candidate honey. of Sciences, St. Petersburg 1993, author - Sporangia).

It is shown that resort treatment of patients with diabetes mellitus complicated by angiopathy of lower extremities, with the use of appliqués from the muds, the temperature of 39-40° has a positive effect on regional blood flow and the overall clinical picture of the disease.

The pathogenesis of late complications of diabetes is quite complex and many-sided and many pathogenetic factors in the development of late complications of diabetes is hyperglycemia and the lack of compensation of the disease. Hyperglycemia leads to activation arbitrage route of glucose metabolism, the nonenzymatic glycosylation proteins and lipoproteins, activation of lipid peroxidation, oxidative stress, lipid and protein metabolism. Due to these is Rzeszow changing the structure of the basal membranes of the vascular endothelium violated endothelium, the processes of microcirculation, tissue hypoxia and processes remodeling of blood vessels, which leads to the development and progression of angiopathies (Efimov A.S., 1987). Research in the last years in the pathogenesis of diabetic angiopathies great importance of the microcirculation as important even high sensitivity to various physiological stimulants. There are new methods of studies of the microvasculature - laser analysis of capillary blood flow, which helps to assess the state of regulatory mechanisms in the microcirculation system in different pathologies, including analysis of microcirculation in different frequency bands: endothelial, neurogenic and myogenic activity (Web, 2002; Aigrain, 2003).

Laser Doppler flowmetry allows you to more deeply explain the mechanism of action of pelotherapy, in particular its temperature component. There are work Teanaway with al., 2002 (proceedings of "the Use of laser Doppler flowmetry in medical practice" - proceedings of the IV all-Russian Symposium, Pushchino may 14-16, 2002, p.8-14)show the effect of different temperature settings on the regulation of vascular tone and including endothelial component, which is of great importance in diabetes mellitus, opredeleniya the amplitude of neurogenic and endothelial activity microvessels in the temperature range of 37-38° C.

Method prototype using mud applications temperature 39-40°on the lower limb according to our data, has a dampening effect on the regulation of endothelial and neurogenic activity - according to laser Doppler flowmetry that patients with diabetes under the influence of pathogenic factors have been oppressed.

Therefore, we propose as an adequate method, potentiating therapeutic effect, to use these contingents application of the muds in the lower limbs not exceeding 37-38°C.

The technical result of the proposed method is to increase the efficiency of treatment of patients with diabetes with angiopathies in the adequate temperature settings pelotherapy optimized regulation of vascular tone due to the activation of endothelial and neurogenic mechanism of the regulation of microcirculatory level.

This technical result is achieved by the fact that I appoint peloidoterapiya in the form of applications in the lower extremity temperature sulfide mud 37-38°s With a duration of 10-15 minutes, No. 10, alternating with carbonate-sulphide bath temperature of 36°for 10-15 minutes, No. 10.

The method is performed as follows. The patient in the face of adequate diet, the dose of antidiabetic drugs or insulin designate flavou mineral water carbon dioxide, average salinity (Essentuki №4), according to traditional methods (200-250 ml 3 times a day for 10-20 minutes before a meal), uglekislotnye mineral baths, temperature 36°C, a single exposure of 10-15 minutes, No. 10, alternating with mud applications on lower limb temperature 37-38°C, a single exposure of 10-15 minutes, a total of 10.

The method is illustrated by the following examples.

1. Patient Abdullayev RB, 55 years of age, was treated in the Essentuki clinic GNIIT with 24.11.05 on 17.12.05 GS diagnosis: diabetes mellitus, type 2, moderate severity, subcompensated complicated distal angioneurotic, ETC I.

Diabetes suffers from 2002, when for the first time after stress has become concerned about dry mouth, thirst, polyuria. When examination revealed increased levels of blood glucose to 12 mmol/l; assigned to the standard glucose-lowering drugs. Blood sugar of 7.5-10 mmol/l, hypoglycemia, one without. Upon receipt of a complaint of weakness, General fatigue, lethargy, periodically dry mouth, leg cramps, numbness in her feet. At the time of admission the patient take diabeton MB 1 tab. 1 time per day.

During examination: HELL 95/70 mm RT. Art., glycemia - 6,9-to 11.3-5.7 mmol/l, glucosuria is 1.5%, when diuresis 1,200 l (18 g/day), cholesterol - 4,79 mmol/l, O. lipids 440 mg%, LDL - 340 mg%, catalase - 42,6%, MDA - 2.54 mmol/l, triglycerides - 1.2 mm/l, LDL - 323 mm/l, VLDL cholesterol - 0,54 mmol/l, LDL LPV - 0,91 2 mm/L. Conclusion RVG: pulse volume slightly raised on the right, moderately increased on the left. The tone of the arterial network is moderately elevated. The tone of the arterioles and precapillaries normal. Venous outflow is obstructed. Conclusion LDF: level of PM within the averages. The prevailing rhythms neurogenic, milennia. The performance index ICR normal. Conclusion AWG (cardiotocography): moderate ischemia heart rate of 56 beats/min Uncertain impact of the divisions of the ANS on the regulation CF (cardiac rhythm).

Patient assigned to the basic therapy, mud packs on the lower limbs, the temperature of 37-38° (motivirovannoe mud), duration 15 minutes, in the course of 10 treatments, alternating with the baths.

As a result of treatment being significantly improved, initial complaints had disappeared by the end of the first week. After 5 days blood sugar dropped to 5.6 mmol/l, was reduced dose CAF, then by the end of the treatment, the blood glucose level reached to 5.8 to 10.6-4.4 mmol/l, in urine - glucosuria, without taking glucose-lowering drugs, cholesterol - 4,99 mmol/l, O. lipids 440 mg%, LDL - 340 mg%, catalase - 52,8%, MDA - 2,96 mmol/l, triglycerides - 1.2 mm/l, LDL - 3,23 mm/l, VLDL cholesterol - 0,54 mm/l, XC LPV - 1,1 2 mm/L. AD to the end of the treatment - 120/80 mm RT. Art. Conclusion RVG: pulse volume reasonable price is but enhanced. The tone of the arterial network is moderately elevated. The tone of the arterioles and precapillaries normal. Venous outflow is saved. Conclusion LDF: level of PM within the averages. The prevailing rhythms neurogenic. The performance index ICR reduced. Conclusion the CWG: the normal heart rate of 63 beats/min Powerful slow waves of short period (10 to 30) with the decline of fast waves. A significant contribution of the parasympathetic division of the regulation CF.

The result of treatment is a significant improvement.

2. Patient Sondikova N.A. was treated in the Essentuki clinic GNIIT with 05.09.050 on 28.09.05. With a diagnosis of diabetes mellitus type 2, moderate severity, subcompensated complicated distal angioneurotic.

Diabetes mellitus type 2 was first identified in 1995, when the examination of complaints of dry mouth, itching elevated blood sugar up to 15 mmol/l was assigned to oral hypoglycemic therapy. Upon receipt of a complaint of weakness, General fatigue, lethargy, periodically dry mouth, bleeding gums, leg cramps, increased blood pressure to 160/100 mm Hg At admission were received maninil 1,75 1 tab. 3 times a day, siofor 850 1 tab. in the evening, the blood glucose levels up to 13 mmol/L.

During examination: glycemia - 13,6-16,0 is 11.9 mmol/l, glucosuria of 2.5% when diuresis 1,020 l (25,5 g/day), holes the Erin - 4.7 mmol/l, O. lipids 480 mg%, LDL - 560 mg%, catalase - 36,6%, MDA - 2.4 mmol/l, triglycerides - 2.2 mm/l, LDL - 1,64 mm/l, VLDL cholesterol - 1.0 mm/l, XC LPV - 1,09 mm/L. Conclusion RVG: pulse volume slightly decreased. The tone of the arterial network is moderately elevated. The tone of the arterioles and precapillaries normal. Venous outflow is saved. Conclusion LDF: level of PM within the averages. The prevailing rhythms neurogenic. The performance index ICR reduced. Conclusion the CWG: the normal heart rate of 76 beats/min Dominant slow wave short-period (>30). Significant vagosympathetic imbalance. A significant increase in the parasympathetic division of the regulation CF.

The patient is assigned to the basic therapy, mud packs on the lower limbs, the temperature of 37-38°s With a duration of 10 minutes on a course of 10 treatments, alternating with the baths.

The treatment results in the well-being of the patient has improved, initial complaints had disappeared by the end of the first week, BP 130/80 mm RT. Art. blood Sugar in the middle of treatment was 9.3 mmol/l, and by the end of the stay at the resort the blood glucose level reached - 6,8-5.3 to 6.6 mmol/l, in urine - glucosuria, cholesterol - 4.0 mmol/l, catalase - 42,2%, MDA - 2.9 mmol/l, triglycerides - 1.6 mm/l, LDL - 1,60 mm/l, VLDL cholesterol - 0,72 mm/l, XC LPV - 1,65 mm/L. AD to the end of the treatment - 130/80 mm RT. Art. Conclusion RVG: pulse blood is impor slightly, reduced right side, normal on the left. The tone of the arterial network is saved. The tone of the arterioles and precapillaries normal on the left. Slightly raised on the right. Venous outflow is saved. Conclusion LDF: level of PM within the averages. The prevailing rhythms neurogenic. The performance index ICR normal. Conclusion the CWG: the normal heart rate is 72 beats/min Balance regulatory systems on the regulation CF.

The result of treatment is a significant improvement.

Demonstrated clinical examples the proposed method is tested in the Essentuki clinic State. Research Institute of balneology (hepatosis) in 40 patients with diabetes mellitus type 1 and 2 (I set), who were appointed by the inventive method of treatment. To control the research was conducted in an identical group of patients with diabetes who received treatment complex prototype with temperature peloid 39-40° (II medical complex). These groups were comparable on these types of diabetes, sex, age, severity and duration of the disease, the degree of compensation (table 1).

Frequency disappearance of symptoms such as thirst, dry mouth, General weakness, fatigue, irritability patients I LK was within 88,5 to 90.0%in the second LC - 75-83,3%. And the disappearance of symptoms characterizing the activity of the cardiovascular system (b is whether in the heart, increased blood pressure, headaches)were statistically significantly higher (P<0,05) in patients I LK in comparison with II LC (table 2). Similarly, the best was the dynamics of symptoms that characterize diabetic angiopathy (PL. 3).

A statistically significant change in glycemic profile and daily glucosuria were seen more frequently in patients who received mud with mud temperature 37-38°in comparison with the prototype. These data are presented in table. 4. It is known that mud with high temperature settings contributes to the activation of sympathetic-adrenal system, and this can prevent the decrease of glycemia.

Similar changes were also observed in relation to lipid metabolism (table 5), the improvement of malondialdehyde and catalase blood in the studied groups, respectively, was equal in the I LK - 72,0 and 77,0%, and the second 56,0 46,0 and% (P<0,05).

When determining the skin temperature of the extremities by means of elektrotermometria best results are obtained when using mud with lower temperature settings (table. 6).

Regional blood flow was estimated by rheovasography (PL. 7), the performance of I LC were significantly better in comparison with the control group.

A special place is the assessment of the dynamics of laser LDF, which was determined in 1 interdigital prom is Jude on the back surface of the foot (PL. 8). As can be seen from the table. 8 endothelial activity (very slow oscillations) is markedly reduced in patients with diabetes compared with healthy ones. After treatment I LK this indicator was significantly increased (P<0,05), while in the II LC is significantly decreased, indicating that the inhibition of endothelial activity of blood vessels at high temperatures mud applications. The efficiency coefficient of the microcirculation and the coefficient of variation M also was significantly increased in the I LK in comparison with the second and microcirculation index, a measure of perfusion) tended to increase. It should be noted that oscillations of heart rate in II LC was significantly increased by the end of treatment, indicating the increase of the load on the cardiorespiratory system and this unwanted effect in diabetes mellitus.

As you know, diabetes is dominated by the activity of the sympathetic-adrenal system. The balance of the autonomic nervous system (ANS) was determined using cardiotocography (CWG). The prevalence of sympathetic ANS was noted in 28 patients in the I LK - 70,0%; and 30 patients in the II LC 75,0%. After the Spa treatment, the balance of the ANS was achieved in 22 patients I LK - 78,6% and only 11 patients II LK - 36,6% (P<0,05), which can be explained by the large trigger influence on the sympathetic who created the system of peloids higher temperatures.

The overall results of treatment were high enough (table), but with substantial improvements were often discharged patients I LK.

Given that the studied groups were comparable on key clinical features and differed only by the assigned treatment, can be considered a higher treatment efficiency I LK due to the combined term effects of drinking mineral water and mud with a temperature of 37-38°With our proposed technique.

The positive effect of the proposed method is confirmed we obtained statistically reliable data concerning the improvement of clinical manifestations of diabetes mellitus and symptoms that characterize the manifestations of diabetic angiopathy, biochemical parameters (the reduction of the glycemic profile, lipid metabolism), changes in skin temperature when elektrotermometria, the dynamics of rheovasography, performance laser LDF limbs and improve cardiotocography. The method is on the presented indicators are more effective in comparison with the prototype and can be used at the stage of sanatorium-resort treatment.

Table 1
Clinical characteristics of patients with diabetes mellitus
Key indicatorsI LK (n=40)II LC (n=40)
abs%abs%
FloorMen20-50,018-45,0
Women20-50,022-35,0
AgeUp to 30 years6-15,08-20,0
31-40 years8-20,09-22,0
41-50 years16-40,012-30,0
51-60 years10-25,011-28,0
Disease durationUp to 5 years7-17,08-20,0
5-10 years28-70,0Lasts 26 to 65,0
>10 years5-13,06-15,0
WeightLight--
Average40-100,040-100,0
The comp is sacia Good12-30,014-35,0
Acceptable28-70,0Lasts 26 to 65,0
poor--
The average height166±2,6165±2,8
The average weight80,5±3,181,5±3,0

2-,27
Table 2
Dynamics of clinical manifestations in patients with diabetes mellitus complicated by distal angiopathy in Spa treatments with mud applications on lower limb
SymptomI LK (40)II LC (40)
nDynamicsnDynamics
ischeznut.reducedb/changesischeznutreducedb/changes
Thirst3125-80,6--3229-,61-3,2
Dry mouth3024-80,06-20,0-2820-71,46-21,42-7,2
Increased appetite188-44,410-55,6-168-50,08-50,0-
Polyuria1610-62,56-37,5-126-50,04-3,32-6,7
General weakness3330-90,93-9,1-3130-96,81-3,2-
Fatigue3429-88,95-11,1-3229-90,61-3,22-6,4
Skin itching1816-88,82-11,2-168-50,08-50,0-
Poor sleep2115-71,46-28,6-189-50,06-33,33-16,4
Irritability3130-96,71-3,3-30 29-96,61-3,4-
Headaches1813-72,25-17,8-126-50,04-33,32-16,7
Joint pain1810-55,56-33,32-11,2168-50,06-37,52-12,5
Pain in the heart1210 83,36-16,7-105-50,05-50,0
Shortness of breath63-50,03-50,0-84-50,024-50 .0
Raising HELL1812-66,66-33,4-168-50,06-37,52-12,5

-
Table 3
Dynamics of symptoms characterizing the presence of diabetic angiopathy in patients with diabetes mellitus treated with the complex Spa treatment using mud applications of different temperatures
The medical complexSYMPTOMS
Pain in legs Chilly extremitiesNumb toesCramps in the leg musclesParesthesiaTrophic disordersThe deterioration of the pulsations in the arteries of the feet
Abs%Abs%Abs%Abs%Abs%Abs%Abs%
I21-52,522-55,019-47,520-50,122-55,016-40,015-37,5
13-61,9*18-81,8*16-84,2*15-75,018-81,8*5-31,35-33,3
8-38,12-13,63-15,85-25,04-18,28-50,05-33,3
-2-13,6---3-18,75-33,3
II22-55,021-52,522-55,021-52,524-60,015-37,521-52,5
13-59,16-28,612-54,515-71,4*12-50,04-26 .76-28,7
9-40,98-38,16-27,36-28 .66-25,06-40 010-47,6
7-33,34-18,2-6-25,05-33 .36-28,7,6
Note: 1 - the line - number of patients with symptom, 2 - disappearance, 3 - reduction, 4 - no change; * - significance of difference P<0,05 - between groups

Table 4
Comparative indices of glycemic profile in patients with diabetes mellitus I and II medical facilities
The group of patientsGlycemia in mmol/l at certain periods of the day at the beginning and end of the treatment
1234
I LCLED110,29±0,6110,91±6,689,81±0,99*9,95±1,01
9,45±0,799,41±0,817,45±0,517,6±0,44
DM28,1±0,3810,0±0,638,3±0,4*8,0±0,38*
7,4±0,378,89±0,516,6±0,376,7±0,31
II LCLED1to 10.09±0,78 9,51±0,5610,1±0,819,3±0,7
9,8±0,59which 9.22±0,669,01±0,658,95±0,65
DM27,9±0,359,87±0,68,2±0,47*8,2±0,34
7,4±0,358,3±0,46,4±0,377,5±0,27
Note.*P<0,05 - significance in the difference at the beginning and end of treatment.

Table 5
Changes in lipid metabolism in patients with diabetes mellitus complicated by angiopathy of the limbs under the influence of Spa treatments with the use of pelotherapy
Lipid fractionsI LCII LC
O. lipidsn608,63±28,6*576,13±23,66
to540, 6L±19,59554,1±of 23.11
Cholesteroln5,99±0,16*5,64±0,17
to5,09±0,165,27±0,16
β-lipoproteinsn504,25±19,56*473,5± 158,8
to430±19,92445±24,145
Triglyceridesn2,259±0,16*USD 2.075±0,16*
to1,60±0,031,66±0,03
HDLn1,065±0,0441,04±0,05
to1,094±0,0531,072±0,05
VLDLn0,89±0,390,78±0,24
to0,66±0,020,74±0,05
LDLn2,99±0,053,1±0,04
to2,6±0,542,8±0,53
CAn4,68±0,33*4,23±0,31
toto 3.58±0,313,9±0,3
Note.*- P<0,05 - significance in the difference at the beginning and end of treatment.

Table 6
The change of skin temperature in patients with diabetes mellitus with use of medical facilities
Index I LCII LC
rightleftrightleft
Hip30,14±0,56*31,18±0,58*30,7±0,5931,5±0,34
31,75±0,3331,9±0,3430,8±0,4731,0±0,48
Tibiawhile 30.92±0,4730,9±0,431,2±0,24*31,5±0,27*
31,11±0,3831,5±0,4432,6±0,2832,6±0,24
Foot (inner surface)27,8±0,54*27,8±0,36*29,3±0,5828,6±0,51
30,7±0,4130,0±0,4530,36±0,4430,7±0,51
Foot (outer surface)30,1±0,41*30,0±0,43*30,62±0,5430,5±0,58
31,87±0,4231,6±0,4131,52±0,4831,48±0,45
Note: the upper values before treatment, the lower after treatment.
* - P<0,05 - significance in the difference at the beginning and end of treatment.

Table 7
The dynamics of rheovasography in patients with diabetes mellitus of different medical facilities
INDICATORSTherapeutic complexes
III
RIthe right limb0,48±0,16**0,48±0,018
0,57±0,020,53±0,03
left0,44±0,016**0,47±0,019
0,57±0,0180,51±0,018
A/Tright16,6±0,25**14.4V±0,51
12,7±0,3116,0±0,33
left14,6±0,27**15,5±0,41
12,7±0,3215,4±0,35
V/aright54,0±1,4253,7±1,5
42,4±1,4852,4±1,3
left52,2±1,455,2±1,47
51,8±1,454,7±1,21
Note: the upper values before treatment, the lower after treatment. The significance of differences is between indicators at the beginning and end of treatment ** P<0,01.

Table 8
Indicators laser LDF skin 1st interdigital gap on the back surface of the foot
IndicatorsDIABETES mellitus type 2Healthy
I groupGroup II
ntonto
M - index of microcirculation perfusion unitsto 7.77±0,568,5±0,637,56±0,767,76±0,69of 5.53±0,66
σ - deviation from the mean value M0,9±0,071,07±0,111,05±0,131,15±0,840,96±0,1
Kvthe % coefficient of variation M12,23±0.814.65±1.07*13.56MHz±1,2614,00±0,1317,36±2,49
Indicators amplitude frequency (A), perfusion units
Andα (very slow oscillations) endothelial activity1,49±0,11,86±0,15*1,57±0,111,7± 0,181,71±0,16
ALF (slow oscillations) neurogenic activity1.22±0.091,39±0,091,36±0,091,26±0,111.44MB±0,14
AHF1 (rapid respiratory oscillations)0,51±0,040,41±0,040,51±0,050,58±0,040,52±0,05
ACF1 (fluctuations of heart rate)0,31±0,030,26±0,030,29±0,020,39±0,04*0,28±0,01
Indicators calculated indexes
ACF1/ALF active mechanism of regulation of blood flow0,21±0,020,25±0,020,25±0,020,24±1,530,34±0,01
AHF1/ALF passive mechanism of regulation of blood flow0,42±0,020,41±0,020,39±0.130,46±0.280,41±0,04
ACF1/M 100% intravascular resistance3,99±0,323,07±0,273,84±0.275,02±0.433,41±0,32
IEM=ALF/AHF1+ACF1 - effectiveness ratio of microcirculation1,65±0,051,85±0,06*1,75±0.08 1,62±0.131,85±0,15
Note: * - significance of differences (P<0.05) in comparison with the indicator at the beginning of the treatment

Table 9.
The effectiveness of Spa treatment of patients with diabetes mellitus complicated by angiopathy of the limbs with the use of pelotherapy
The observed groupThe number of patientsThe result of the treatment
Significant improvementImprovementNeznachit. improvementWithout improvements
abs%abs%abs%abs%
I LC401025,0*3075,0----
II LC40615,03075,0410,0--
Note: * - significance of difference P<0,05.

Method for the treatment of patients with sah is rnym diabetes, complicated by angiopathy of the lower extremities by internal and external use of mineral waters, characterized in that designate peloidoterapiya in the form of applications in the lower extremity temperature sulfide mud 37-38°With a duration of 10-15 minutes No. 10, alternating with carbonate-sulphide bath temperature of 36°10-15 min No. 10.



 

Same patents:

FIELD: organic chemistry, medicine, neurology, pharmacy.

SUBSTANCE: invention relates to novel hydrogenated pyrrolo[4,3-b]indoles of the general formula (1): , their racemates, optical isomers, geometric isomers, pharmaceutically acceptable salts and/or hydrates that can be used, for example, in treatment and prophylaxis of different neurodegenerative diseases, such as Alzheimer's syndrome. In the general formula (1): a dotted line with accompanying unbroken line represents ordinary or double bond; R1 and R2 represent independently of one another substitutes of amino group chosen from hydrogen atom, possibly substituted (C1-C6)-alkyl substituted possibly with aryl, possibly substituted phenyl, possibly substituted carbonylamino or thiocarbonylamino group, substituted acyl, possibly substituted aryl sulfonate wherein substituted in indicated R1 and R2 are chosen from (C1-C6)-alkyl, halogen atoms, nitro, carboxy, alkoxy group, aryl; R1n represents one or some similar or different substituted of cyclic system chosen from hydrogen atom, alkyl, aryl, cyano group, halogen atom, 5-6-membered nitrogen-containing heteroaryl. Also, invention relates to methods for synthesis of these compounds, pharmaceutical compositions and their using, and to using compounds in libraries with their using.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions, improved methods of synthesis.

20 cl, 2 tbl, 12 ex

FIELD: organic chemistry, medicine, pharmacology.

SUBSTANCE: invention relates to compound of the formula (I): or (II): wherein R1 and R2 are chosen independently from hydrogen, optionally substituted alkyl or the group: -D-E wherein R represents a covalent bond or alkylene; E represents optionally substituted alkoxy-group, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted alkenyl or optionally substituted alkynyl under condition that if D represents a covalent bond then E can't represents alkoxy-group; R3 represents hydrogen atom, optionally substituted alkyl or optionally substituted cycloalkyl; X represents optionally substituted arylene or heteroarylene; Y represents a covalent bond or alkylene wherein one carbon atom can be substituted optionally for -O-, -S- or -NH-, and optionally substituted hydroxy-, alkoxy-, optionally substituted amino-group or -COR wherein R represents hydroxy-, alkoxy- or amino-group under condition that if an optional substitute represents hydroxy- or amino-group then it can't be adjacent with a heteroatom; Z represents hydrogen atom, optionally substituted monocyclic aryl or optionally substituted monocyclic heteroaryl under condition that Z represents hydrogen atom only under condition that Y represents a covalent bond, and X represents optionally substituted 1,4-pyrazolene, and under condition that if X represents optionally substituted arylene then Z represents optionally substituted monocyclic heteroaryl. Also, invention describes a method for treatment of the morbid state by inhibition of adenosine receptors describes as A2B based on compounds of the formula (I) or the formula (II). Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable medicinal properties of compounds.

32 cl, 35 ex

FIELD: medicine, experimental cardiology.

SUBSTANCE: one should intragastrically introduce claritromycin at the dosage of 30 mg/kg 15 min before coronary occlusion in the course of experimental coronary occlusion myocardial infarction. The innovation provides significant decrease of the necrosis area due to cardioprotector action of claritromycin.

EFFECT: higher efficiency.

1 ex, 1 tbl

FIELD: medicine, experimental cardiology.

SUBSTANCE: the present innovation deals with restricting the necrosis area in the course of experimental coronary occlusion myocardial infarction due to intragastric introduction of roxytromycin at the dosage of 30 mg/kg 15 min before coronary occlusion. The innovation provides significant decrease of the necrosis area due to cardioprotector action of roxytromycin.

EFFECT: higher efficiency.

1 ex, 1 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to pharmaceutical compositions containing inhibitor of cholesterol esters-transporting protein (CETP) and a water-insoluble additive increasing its concentration. As CETP inhibitor invention uses S-{2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl}-2-methylpropanethioate or a prodrug that forms in vivo S-{2-([[1-(2-ethylbutyl)cyclohexyl]carbonyl]amino)phenyl}-thiol. A water-insoluble additive increasing the concentration of CETP inhibitor represents crospovidon. Indicated compositions show improved bioavailability in medium wherein they are used that allows using in methods for treatment of cardiovascular disorders.

EFFECT: improved and valuable pharmaceutical properties of compositions.

13 cl, 11 tbl, 5 dwg, 9 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention describes novel derivatives of triazolo[4,5-d]pyrimidine of the general formula (I): wherein R1 means (C3-C5)-alkyl that can be substituted with halogen atom; R2 means phenyl that can be substituted with fluorine atom; R3 and R4 are similar and mean hydroxy-group; R means XOH wherein X means -CH2, -OCH2CH2 or a bond, or their pharmaceutically acceptable salt or solvate of solvate of such salt under condition that when X means -CH2 or a bond then R1 doesn't mean propyl group; when X means -CH2 and R1 means -CH2CHCF3, butyl or pentyl groups then phenyl group at R2 must be substituted with fluorine atom; when X means -OCH2CH2 and R1 means propyl then phenyl group at R2 must be substituted with fluorine atom. Also, invention describes a pharmaceutical composition based on these compounds, method for their synthesis and novel intermediate compounds of the formula (II) , (V) and R-(R*,R*)-2,3-dihydroxybutanedioate (1:1) of compound of the formula (III): . Also, invention relates to a method for treatment of diseases mediated by P2T-receptors, such as myocardium infarction, prophylaxis or propagation of tumors and others.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions, improved method of synthesis.

15 cl, 9 ex

FIELD: organic chemistry, chemical technology, medicine, pharmacy.

SUBSTANCE: invention relates to novel hydrogenated azepino[4,3-b]indoles of the general formula (1): , their racemates, optical isomers, geometric isomers and their pharmaceutically acceptable salts and/or hydrates. In the general formula (1) a dotted line with accompanying unbroken line represents a simple or double bond; R1 and R2 represent independently of one another substitutes of amino-group chosen from hydrogen atom, possibly substituted (C1-C8)-alkyl possibly substituted with aryl, 5-6-membered azaheterocyclyl, (C1-C8)-alkoxycarbonyl, possibly substituted phenyl, possibly substituted carbonylamino- or thiocarbonylamino-group, substituted acyl, (C1-C8)-alkylsulfonyl, possibly substituted arylsulfonyl and wherein substitutes in indicated R1 and R2 are chosen independently from (C1-C8)-alkyl, halogen atoms, nitro-, carboxy-, alkoxy-group, aryl; Rin represents one or some similar or different substitutes of cyclic system chosen from hydrogen atom, (C1-C8)-alkyl, (C6-C10)-aryl, halogen atom, 5-6-membered azaheterocyclyl. Also, invention relates to methods for synthesis of these compounds, their using and pharmaceutical composition and libraries of compounds. Synthesized compounds possess neuroprotective, cognitive-stimulating and anti-histaminic properties and can be used in treatment of different neurological disorders, allergic and autoimmune diseases, for example, for memory improvement.

EFFECT: valuable medicinal and biological properties of compounds and pharmaceutical composition, improved method of synthesis.

25 cl, 2 tbl, 12 ex

FIELD: biologically active substances.

SUBSTANCE: invention relates to improved method of obtaining total amount of phenol acid including following steps: (a) multi-rooted sage is extracted with water and filtered; (b) filtrate is placed in polyamide column and washed with water to neutral reaction, wash water is removed, and polyamide column is eluted with weak aqueous alkali solution, and obtained fractions are connected; (c) alkali fractions obtained in step (b) are acidified and placed in absorption column with macroporous resin, column is washed to neutral state, wash water is removed, column is eluted with aqueous or anhydrous lower alcohol, eluent is collected, evaporated at reduced pressure to remove alcohol, and dried. Yield of final product exceeds 4% based on amount of crude drug and content of total amount of phenol acid exceeds 80%. Thus obtained total amount of phenol acid can be used as drug for prevention and treatment of brain vessel diseases.

EFFECT: enlarged resource of vegetable material for preparation of vascular drugs.

15 cl, 7 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to using inhibitor of absorption of sterol of the formula (VIII): or its pharmaceutically acceptable salts or solvates. This compound is used for preparing a medicinal agent that is used for decreasing the concentration of at least one sterol in plasma or tissues or their mixture of mammals wherein this sterol is not cholesterol or 5α-stanol. Also, invention relates to a method for decreasing the concentration of at least one sterol in plasma or tissue and involves administration to mammal a compound of the formula (VIII) in the dose 0.3-10 mg/1 kg of body mass per 24 h. Decreasing the content of content of indicated sterols in plasma or tissues provides prophylaxis or attenuation of such states as arteriosclerosis, risk of cardiovascular attack.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

19 cl, 6 tbl, 2 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to using compounds of (R,S)-2-arylpropionic acids of the formula (Ia) , and their (R)- and (S)-isomers as inhibitors of neutrophile (PMN leukocytes) chemotaxis induced by IL-8. These compounds elicit unexpected ability to inhibit effectively IL-8-induced chemotaxis and degranulation of neutrophiles being without significant effect on activity of cyclooxygenases. These compounds can be used in treatment of such diseases as psoriasis, ulcerated colitis, melanoma, chronic obstructive pulmonary disease, bulla pemphigus, rheumatic arthritis, idiopathic fibrosis, glomerulonephritis, and for prophylaxis and treatment of damages induced by ischemia and reperfusion.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

9 cl, 3 tbl, 43 ex

FIELD: medicine.

SUBSTANCE: method involves giving magnesium-sodium-hydrocarbonate mineral water of moderate mineralization degree at room temperature in the amount of 150-200 ml. 20-30 min later alternating electromagnetic field operating in low frequency bandwidth of 0.022 Hz-270 kHz is administered in scanning mode of 43 produced by Rematherp apparatus. The total treatment course is 8-10 procedures long.

EFFECT: enhanced effectiveness of treatment; stimulated reparative processes in esophageal mucous membrane.

FIELD: medicine.

SUBSTANCE: method involves prescribing low mineralization water to drink and mud applications on liver and gallbladder area. The liver and gallbladder area is to be additionally exposed to extremely high frequency bandwidth electromagnetic field treatment as 4-6 s long pulses and pauses. Then, heart zones of Zakharyin-Gedda are treated within 5-10 min in nonmodulated mode. Then paired biologically active points of gallbladder meridian VB 24 (Ri-yue) are treated 3-5 min long per each biologically active point in modulation mode as 4-6 s long pulses and pauses. The total treatment course is 15 daily procedures long.

EFFECT: enhanced effectiveness of anti-inflammatory biliary excretion system treatment; improved blood microcirculation processes, lipid peroxidation processes; accelerated injured functions recovery.

3 tbl

FIELD: medicine.

SUBSTANCE: method involves applying therapy course containing iodine-bromine baths and vaginal irrigations given every other day. Electrophoresis is administered in days free of baths and irrigations after 2 adaptation days with silt mud enriched in hydrogen sulfide water containing hydrogen sulfide in concentration of 350 mg/l. The treatment is applied to hypogastric and lumbosacral region at the level of L4-S2 vertebrae. Electric current intensity is equal to 0.05-0.1 MA/cm2 during 20 min. The total treatment course is 8 balneo- and physioprocedures long.

EFFECT: reduced peritoneal commissure process intensity; normalized vegetative nervous system and ovarian functions; improved cellular and humoral immunity; increased female fertility.

5 tbl

FIELD: medicine.

SUBSTANCE: method involves crushing shungit mineral to fraction size of 5-10 mm large and placing it into drinking water in 1:15-1:20 proportions by volume and keeping them together at room temperature 3 days long. The extract is saturated with colloid silver ions to concentration of 5000 mcg/l and 100% Volatile Australian tea tree oils are next added in the amount of 15-30% by volume.

EFFECT: accelerated wound healing including persistent ones.

2 cl, 2 dwg

FIELD: medicine, gastroenterology.

SUBSTANCE: it is necessary to apply omeprasol 20 mg twice daily, furasolidone at 100 mg thrice daily and hydrogen sulfide solution at concentration of 10 mg/l per 150 ml thrice daily. Therapeutic course corresponds to 10 d. Due to additional anti-Helicobacter impact of hydrogen sulfide solution at hydrogen sulfide concentration being 10 mg/l the present innovation provides efficient eradication of Helicobacter pylori without using antibiotics.

EFFECT: higher efficiency of therapy.

3 ex

FIELD: medicine, gynecology.

SUBSTANCE: the present innovation deals with treating puerperal obesity-manifesting neuroendocrine syndrome. The method includes fractional nutrition, terrencur per 7.8-8.5 km/d, mineral baths and gynecological irrigations at applying hydrocarbonate-sulfate sodium-calcium mineral water of Slavyanovski well of 35-38°. During the whole course of therapy it is necessary to have the intake of the same mineral water thrice daily about 30-40 min before meals. One should carry out acupuncture reflexotherapy due to the second brake method during maximal activity of renal canals, those of urinary bladder, liver and pancreas. Acupuncture reflexotherapy should be alternated according to the days of affecting key points, group LO of "magic meridians", "key points" on the main syndrome. The innovation improves therapeutic result due to affecting autonomic nervous system.

EFFECT: higher efficiency of therapy.

3 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: method involves prescribing drinking radon-containing mineral water distinguished by radon activity of 185-370 kBq/l in the amount of 100 ml 3 times a day. Then, radon baths are given where radon activity is of 0.75-2.25 kBq/l, temperature is 36-37°C, procedure duration is 10-15 min. Then, vacuum depression of 4-9 atm with succession frequency of 15-25 pulses per 1 min and alternating sinusoid current of 100-200 Hz, current intensity of 20-40 mA and duration of 12-15 min is applied to kidney region and injured ureter segment region in everyday mode with 10-12 procedures long treatment course.

EFFECT: increased stimulated action to functional renal pacemaker and neuromuscular apparatus; higher percent of stone excretion.

4 cl

FIELD: medicine.

SUBSTANCE: method involves carrying out vacuum massage of prostate with an apparatus. Tampons with 40-45°C hot sulfide mud taken from Sucsun pond are additionally rectally introduced for 20-30 min. The total treatment course is 8-10 procedures long. Daily microenemas are prescribed with mineral water at 36°C in a 10 procedures long course.

EFFECT: enhanced effectiveness of treatment.

FIELD: medicine, gynecology.

SUBSTANCE: patients should be suggested to take radon procedures as baths, gynecolopgical irrigations, microenemas, laserotherapy in autoresonance mode at altering frequency of laser apparatus independently against frequency characteristics of human body, at wave length of 0.89 mcm, power of 10 W onto area of uterine projection in case of genital endometriosis and uterine myoma at exposure of 15 min and onto mammary glands in case of diffuse proliferative mastopathies. Impact fields should be chosen by sectors ranged 10-16 per 10-15 sec for each impact field. Local therapy should be conducted about 2.5-3 h after taking radon procedures successively, not earlier. The first stage - baths with malavit at 1:5 dilution at exposure of 15 min. The second stage - after removing the solution out of vagina it is necessary to introduce malavit gel at a tampon for 4-6 h. The whole therapy should be carried out together with internal intake of mineral water 30-60 min before meals thrice daily per 3.5 mg/kg body weight. The innovation enables to achieve prolonged remission, normalize hormonal level in blood and duration of the second phase of the cycle and decrease cholesterol level in blood.

EFFECT: higher efficiency of correction.

1 dwg, 4 ex

FIELD: medicine, gastroenterology.

SUBSTANCE: the present innovation deals with prescribing dietetic nutrition, drinking mineral water and mineral baths for a patient. Additionally, it is necessary to prescribe relaxation therapy at the quantity of 12 procedures in a massage chair for 18 min, moreover, in the course of the first 2 d of therapy the impact should be made in the massage chair only, and during the next days - in the morning the impact is in the massage chair and 2-3 h later - with the help of apparatus "Zen Trainer" for about 15-20 min. The innovation suggested enables to achieve increased ATP level, decreased AMP level, increased energy charge and positive dynamics according the main values of the level and the ratio of nucleotides.

EFFECT: increased efficiency of restorative therapy.

2 ex, 4 tbl

FIELD: medicine.

SUBSTANCE: method involves starting magnetic laser therapy beginning from the second treatment day. Apparatus having magnetic head is used at frequency 80 Hz. Segmental vertebral column reflex region is irradiated. Paravertebral zones are irradiated in the vicinity of C5-D2 in predominant upper extremity articulation injury cases; in the vicinity of L1-S3 in predominant lower extremity articulation injury cases. Scanning method is applied with speed not exceeding 2 cm/s, spending 4 min for each field. Stable local radiation is applied to the most severely injured pair of articulations over articulation fissure projection zones spending 3 min for each zone during three days in succession. Then, magnetic laser therapy sessions are given every other day with hydrogen sulfide baths being added beginning from the fourth treatment day making 10 min long pauses between physiotherapeutic procedures. Amplipulse pelotherapy with silt mud enriched in hydrogen sulfide water having hydrogen sulfide concentration of 350 mg/l is applied to the same zones using Amplipulse apparatus. The total treatment course is 10 magnetic laser therapy procedures, 8 amplipulse pelotherapy and 8 balneo procedures long.

EFFECT: marked anti-inflammatory and anesthetic effectiveness; improved local and segmental trophic action; avoided adverse side effects.

9 tbl

Up!