Method for correcting increased levels of anxiety and depression in patients with arterial hypertension accompanying type 2 diabetes mellitus

FIELD: medicine.

SUBSTANCE: correcting increased levels of anxiety and depression in the patients with arterial hypertension accompanying type 2 diabetes mellitus is ensured by combining a standard drug treatment and administering Kudesan 60 mg a day for two months.

EFFECT: method provides the effective correction of anxiodepressive conditions in the given category of patients that in turn enables normalising blood pressure more effectively by reducing the negative psychosomatic effect.

1 ex, 2 tbl

 

The invention relates to medicine, internal medicine and can be used for the correction of high levels of anxiety and depression in patients with arterial hypertension(AH) and diabetes mellitus(DM) type 2.

Mental health problems of society are inextricably linked with diseases of the cardiovascular system. A correlation between increased stress levels and increase depressive disorders, and increased morbidity and mortality from coronary heart disease [6]. Correlation between arterial hypertension (AH) and depression [6, 10]. Therefore, in modern conditions the problem of depression is seen as a key not only in psychiatry but also in General medicine [10]. Anxiety, like depression, is associated with increased risk of hypertension [9, 14]. It is important to note the close comorbidity of depressive and anxiety disorders. Depression is almost always accompanied by disturbing symptoms [10].

J. Das-Munshi et al. (2007) [14] to study the prevalence of mental disorders in patients with somatic conducted a large population study among 8580 inpatient. Suffered from diabetes mellitus 249 (3%) patients. It was found that mental disorders occur in patients with diabetes is 1.5 times more often than in the General population, and anxiety-depressive disorders - � 1.7 times. The results of the study suggests that anxiety and depressive disorders and related mental pathology observed in diabetic patients, reduces their social adaptation, quality of life and leads to irregular and poor quality control by the patients own state.

Note that most researchers detected an increased prevalence, increased level of anxiety and depression in patients with arterial hypertension on the background of diabetes.

Despite the high prevalence of anxiety and depressive disorders in General medical network in Russia in the vast majority of cases are not diagnosed and therefore not treated. This situation is largely due to a lack of awareness among General practitioners about the prevalence, modern facilities for diagnosis and therapy of anxiety and depressive disorders. Regional aspects of the epidemiology of anxiety and depressive disorders, risk factors for cardiovascular disease (CVD), their interaction has not been studied.

A study of the sources of patent and scientific and medical information sources did not reveal the methods of correction of the raised levels of anxiety and depression in patients with arterial hypertension on the background of type 2 diabetes.

A new technical task is to develop a method which allows the Kli�algebraic practice to conduct a significantly positive drug correction of anxiety and depressive disorders in patients with arterial hypertension on the background of type 2 diabetes.

To solve the problem in the way of high levels of anxiety and depression in patients with arterial hypertension on the background of diabetes mellitus type 2, on the background of standard therapy additionally enter product "Qudesan" in a dose of 60 mg per day for two months.

The method is as follows.

At the outpatient stage is carried out a complex of measures: history taking and clarification of patient complaints; palpation and auscultation of the heart and major blood vessels; blood pressure measurement on the upper limbs according to method N. With.Korotkova; registration of ECG, conducting Echocardiography. Conduct biochemical analysis of whole plasma, fasting: exploring the level of glucose, glycosylated hemoglobin, lipid profile (cholesterol, triglycerides, LDL, HDL), indicators of blood coagulation (PI, APTT, fibrinogen), electrolytes (K, Mg). Also patients are testing, by completing a medical questionnaire for special purposes. Use the HADS questionnaire and Samoobrona depression CED-S.

Assessment of the severity of the condition of a patient on the Hospital scale of anxiety and depression (HADS)

The scale is composed of 14 statements (serving 2 podskalny: "anxiety" and "depression". Each of the statement corresponds to 4 possible answers that reflect gradations in the severity of symptom and encoded on n�rasteniy the severity of the symptom from 0 (absence) to 3 (maximum severity) [14].

In interpreting the results already take into account the total index for each podskali, allocate 3 field values are:

- 0-7 - "norm" (the absence of a significantly severe symptoms of anxiety and depression);

- 8-10 - "subclinical anxiety/depression";

- 11 and above as "clinically severe anxiety/depression."

Assessment of the severity of depressive disorder spend on Samoobrona CED-S.

As a screening instrument to identify depressive disorders are also using the questionnaire CED-S (Center for Epidemiologic Studies-Depression), developed in the US in 1977 [1]. If the patient is gaining 19 points or more, he suffers from depressive disorder: slight depression at values 19-26 points expressed depression at values of more than 26 points.

After evaluation of interest to us patients in addition to standard Protocol of treatment of hypertension on the background of type 2 diabetes (beta-blockers, ACE inhibitors, calcium antagonists, inhibitors of angiotensin II receptor, etc., hypoglycemic agents) and in the presence of coronary heart disease (nitrates, statins, cardioprotective agents), appoint a mitochondrial coenzyme CoQ10 - drug "Qudesan" on 60 mg a day for two months.

The proposed method of correction of the raised levels of anxiety and depression in patients hypertension on the background of diabetes mellitus type 2 is illustrated with a concrete example.

Example 1. Patient R., woman, 62 years old, cloakroom. Is registered with a General practitioner with a diagnosis of coronary artery disease: SN FC II. Hypertension stage III, the achieved degree of AH 2, risk 4. Diabetes mellitus type 2, target level of HbAlc < 7.5 per cent. The obesity of the second degree. Is on standard therapy of hypertension and DM. From history: hypertension affects about 10 years, diabetes mellitus 5 years, coronary heart disease about seven years. Complained of increased blood pressure up to 150/110 mm Hg.CT., headaches, dizziness, occasionally during exercise discomfort behind the breastbone, shortness of breath. Accepts cardflex 20 mg per day, Prestarium 5 mg, ciofora 1000 1 t - 2 times per day, maninil 3.5 mg 1 t - 2 times per day. Drugs taking constantly. Objectively: the condition is satisfactory, vesicular breathing, no rales, heart sounds clear, rhythmic, HELL 155/114 mm Hg.PT. General analysis of blood leukocytes to 4.2×109/l; erythrocytes - 4,7×1012/l; hemoglobin 134 g/l; the platelet count is 261×109/%; ESR - 4 mm/h. Biochemical analysis of blood: glucose - 6,4 mmol/l; glycosylated hemoglobin - 6,21%; cholesterol - 6,07 mmol/l; triglycerides - 1.56 mmol/l; LDL - 4.5 mmol/l; HDL - 1.3 mmol/l; PETIT 98,3%; APTT was 30.3 C; fibrinogen - 3,24 g/l; potassium - 4,05 mmol/l; magnesium - 0,79. Urinalysis: color - yellow, transparent, density 1012, protein is not specified, sugar - not determined; MICR�scopy: leukocytes - 0-1-0, erythrocytes 0-1 in the field of view. Conclusion: hyperglycemia, hypercholesterolemia. ECG: sinus rhythm, right, HR - 62 in 1 minute, the deviation of the EOS left, signs of left ventricular hypertrophy, signs of myocardial ischemia. ECHO: a slight extension of the ascending aorta, the aortic wall is sealed. The chambers of the heart are not expanded. The contractility of the left and right ventricles are normal. Violation of local contractility (alone) no. Diastolic dysfunction (impaired relaxation). Small concentric left ventricular hypertrophy. Valves without modification, are functioning normally. Pericardium - without features.

The patient on the background of standard therapy (beta-blockers, ACE inhibitors, calcium antagonists, inhibitors of angiotensin II receptor, etc., hypoglycemic agents), was appointed Qudesan drug at a dose of 60 mg per day for two months. According to the proposed method before the treatment was determined by the level of anxiety on a scale HADS 12 - symptomatic; the level of depression 9 points - subclinical expressed. Determining the level of depression on the CES-D scale 22 points, which corresponds to mild depression. After one year of follow-up examination was repeated. Objectively: the condition is satisfactory, vesicular breathing, no rales, heart sounds clear, rhythmic, HELL 123/86 mm Hg.PT.General blood analysis l�Ecocity - 4,4×109/l; erythrocytes - 4,8×1012/l; hemoglobin - 136 g/l; platelets - 258×109/%; ESR - 2 mm/h. Biochemical analysis blood glucose was 5.2 mmol/l; glycosylated hemoglobin - 5,44%; cholesterol - 5,09 mmol/l; triglycerides - 1,51 mmol/l; LDL 3.2 mmol/l; HDL - 1.6 mmol/l; PETIT 96,9%; APTT - 29; fibrinogen - 3.19 g/l; potassium was 4.1 mmol/l; magnesium - 0,92. Urinalysis: color - yellow, transparent, density 1014, protein is not specified, sugar - not determined; microscopy: leucocytes - 0-1-0, erythrocytes 0-1 in the field of view. Conclusion: indicators General and biochemical blood analysis, urinalysis within normal limits. ECG: sinus rhythm, right, HR - 62 in 1 minute, the deviation of the EOS to the left, the signs of hypertrophy of the left ventricle. ECHO: a slight extension of the ascending aorta, the aortic wall is sealed. The chambers of the heart are not expanded. The contractility of the left and right ventricles are normal. Violation of local contractility (alone) no. Diastolic left ventricular function is not impaired. Small concentric left ventricular hypertrophy. Valves without modification, are functioning normally. Pericardium - without features. Determining the level of anxiety on a scale HADS 6 points - which corresponds to the norm; the level of depression by 5 points, which corresponds to the norm. Determining the level of depression on the CES-D scale 15 points, which corresponds to the norm. Get�record data in this case suggest about the treatment of arterial hypertension on the background of diabetes mellitus type 2 standard therapy (beta-blockers, ACE inhibitors, calcium antagonists, inhibitors of angiotensin II receptor, etc., hypoglycemic agents), complementing the medication Qudesan on 60 mg a day for two months has a significant positive effect on the characteristics of the emotional state of the patient.

The proposed method of assessing the level of anxiety and depression in patients with arterial hypertension on the background of diabetes mellitus type 2, and the method of its correction with the use of mitochondrial coenzyme CoQ10 is based on the analysis of clinical trial data and the results of a study of the literary sources.

Drug "Qudesan", according to the instructions for use, has the following characteristics:

Registration # LSR-003092/10,

Trade name: "Qudesan",

Chemical rational name: Ubidecarenone,

Dosage form: drops for oral administration.

Description: Transparent liquid of yellowish-orange color with a slight opalescence.

The composition of the drug "Qudesan": Active substance: ubidecarenone 30 mg. inactive ingredients: alpha-tocopherol acetate - 4.5 mg, ascorbyl palmitate - 1.0 mg, macrogol glycerylmonostearate (RH-40) - 105,0 mg, sodium benzoate - 2.0 mg, citric acid (food grade) - 1.6 mg, purified water to 1 ml.

Pharmacotherapeutic group: non-glycoside Cardiotonic agent structure ATC Code: SEV.

Pharmacological properties

Pharmacodynamics

The drug, normalizing myocardial metabolism, reduces tissue hypoxia. Ubidecarenone (CoQ10, ubiquinone) is a naturally occurring substance, which is a vitamin-like coenzyme. Ubidecarenone is an endogenous substrate that participates in the transfer of electrons in the transport chain redox processes, in the process of exchange of energy in the reaction of oxidative phosphorylation in the respiratory chain of mitochondria of cells. Participates in the processes of cellular respiration by increasing the synthesis of ATP. Have clinically significant antioxidant activity. Protects the lipids of cell membranes from peroxidation. Reduces the area of myocardial damage in conditions of ischemia and reperfusion. Ubidecarenone prevents prolongation of the QT interval, improves exercise tolerance. Due to the endogenous synthesis 100% satisfaction the body's need for CoQ10 occurs only up to the age of 20. The concentration of coenzyme Q10 is reduced in elderly patients and in a variety of diseases in both adults and children.

Pharmacokinet�ICA

Data on the pharmacokinetics of the drug is not provided.

Indications for use:

Adults:

For prevention and complex therapy of various diseases of the cardiovascular system:

- chronic heart failure (including dilated cardiomyopathy);

- Coronary artery disease, including myocardial infarction (during the period of rehabilitation therapy);

- arrhythmias;

- arterial hypertension;

- the period of preparation for heart surgery (coronary artery bypass grafting, heart defects).

Children older than 1 year:

For prevention and complex therapy:

- diseases of the cardio-vascular system: arrhythmia, chronic heart failure (including dilated cardiomyopathy), the period of preparation for heart surgery (congenital and acquired);

- diseases of the gastrointestinal tract: chronic gastroduodenitis;

- kidney disease: chronic pyelonephritis, metabolic nephropathy;

- diseases of the nervous system (including hereditary neurodegenerative diseases: migraine, disorders of the autonomic nervous system (NDCs), mitochondrial encephalomyopathy (MELAS syndrome), a syndrome Laga, tuberous sclerosis, congenital myopathies, muscular dystrophy.

In the treatment of diseases associated with metabolic disorders:

- ACTE�quarter syndrome;

- the recovery period after a serious illness and surgery.

The drug Qudesan® should be taken orally 1 time per day during meals in the morning, pre-dissolved in a small amount of boiled water or another beverage at room temperature. For the purpose of prevention and making up a deficiency of coenzyme Q10 to adopt, in accordance with the recommendations. In complex therapy of various diseases Qudesan® should be taken depending on the age of all the stated indications in accordance with the recommendations. Time course of the drug Qudesan is 2-3 months. Repeated courses on the recommendation of a doctor.

Manufacturer: CJSC "aquion, Russia 125040, Moscow, 3-ya ulitsa Yamskogo polya, d. 28

Coenzyme Q10 is a natural substance for the body. It is produced and present in all cells of the body. Unfortunately, with age, the production of CoQ10 in the body declines: after 25 years becomes a significant deficiency Q10. As a result of impaired energy production and preservation of cellular structures. As a consequence, there is fatigue, reduced activity, disrupted the work of the heart, weakens the immune system, etc. Q10 Deficiency and the decrease of its synthesis may occur due to various diseases, medications, large physical disturbance�s metabolism, etc. In addition, regardless of health and lifestyle, synthesis of Q10 in the human body begins to decline with age. To prevent and to eliminate the deficit Q10 doctors recommend supporting agent - medications Q10. The presence of Q10 in all cells, natural origin ensures the safety of its use. In addition, CoQ10 has proven effective in combating age-related changes. Unlike cosmetic products, which have recently become often include coenzyme Q10, if ingestion occurs a complex effect on the body on a deeper level. Qudesan is an effective source of Q10. Its effectiveness is confirmed by the experience of domestic cardiologists, who for several years used the drug in the prevention and the treatment of cardio=cardiovascular disease. Q10 is a fat - soluble substance (i.e. absorbed with fats). Therefore, most of the drugs on the basis of the Q10 has to be taken with fatty foods, which is not always possible.

Russian specialists have developed and patented a technology enabling the transfer of poorly digestible fat-soluble substance Q10 in a water soluble form, for optimal absorption and easy to use. This technology is used in the production of Cudesna. Thanks to water-soluble forms� of CoQ10 Qudesan able to more effectively compensate for a deficiency of Q10 in the human body.

As a result of a clinical study, we found a new property of the drug on the basis of coenzyme Q10, namely its ability to correct high levels of anxiety and depression in patients with arterial hypertension on the background of type 2 diabetes. This property was discovered through the observation of patients at the outpatient reception in municipal budgetary health care institution "Hospital 2". Concluded that the indication for prescription medicines "Qudesan" is an increased level of anxiety and depression in patients with arterial hypertension on the background of type 2 diabetes.

The study included 120 patients with essential hypertension (EH), associated with diabetes type 2 diabetes mellitus with inadequate control of blood pressure (BP). The diagnosis of essential hypertension was verified in accordance with the classification of hypertension and criteria for risk stratification of cardiovascular complications of the third revision (Recommendations GFCF, 2010). In cases of an associated clinical condition (ASC) GB and CHD, the diagnosis of ischemic heart disease, stable angina was determined in accordance with the clinical recommendations of the second review of GFCF, 2010. Functional class (FC) angina mouth�was avowals according to the classification proposed by the Canadian Association of cardiologists (CCS). The diagnosis of diabetes mellitus type 2 was based on the who classification, 1999 with additions.

Criteria for inclusion in the study. Patients with GB had a second degree of increase of AP on the background of type 2 diabetes, mild to moderate severity in the stage of compensation at the level of glycated hemoglobin is 6.25%. Patients had a relatively high frequency of comorbidities and risk factors, complicating the course of hypertension. All patients were on a baseline antihypertensive therapy, mainly in patients received various combinations of antihypertensive agents (beta-blockers, ACE inhibitors, calcium antagonists, inhibitors of angiotensin II receptor). In addition, the patients took the drugs for the treatment of concomitant pathology (lipid-lowering drugs, nitrates, glucose-lowering drugs). Mandatory criterion was the patient's consent to participate in the study.

Exclusion criteria from the study. Failure to meet criteria of inclusion, participation in clinical trials of other drugs with less than 3 months old, the refusal of a patient to perform the study Protocol, cancer, mental disorders, drug or narcotic dependence, use of drugs without prescription-the study�tell, the presence of tuberculosis or systemic connective tissue diseases, severe violations of rhythm and conductivity, implanted EX, severe liver or renal failure, patients with pathology and substitution therapy with thyroid hormones, uncontrolled hypertension, pregnancy, severe anemia.

Patients-men and women with arterial hypertension on the background of diabetes mellitus type 2. When contacting the clinic patients who meet the criteria of inclusion and exclusion, randomly distributed into 2 groups: group 1 (n=60) (age of 57.2±5.5 years). The patients were administered standard therapy of treatment of hypertension on the background of diabetes mellitus type 2; group 2 (n=60) (age of 57.2±5.5 years). Standard therapy of treatment of hypertension on the background of type 2 DM was supplemented medicine "Qudesan" for 2 months at 60 mg a day. Clinical examination of patients was performed according to "guidelines on prevention, diagnosis and treatment of arterial hypertension" [3]. To perform all procedures without prior written consent.

The results of the study are illustrated by Tables 1, 2.

Table 1 presents the data of clinical parameters in the treatment of arterial hypertension on the background of diabetes mellitus type 2 on a standard Protocol and dobavleniyu the standard treatment Protocol of the drug "Qudesan"

Note: # p<0,05; ## p<0.01 compared with the indicators of the groups;

* p<0,05; ** p<0.01 compared to the baseline.

Table 2 presents the data of clinical parameters in the treatment of arterial hypertension on the background of diabetes mellitus type 2 on a standard Protocol and when added to the standard treatment Protocol of the drug "Qudesan".

In the tables presented in the comparison of average data changes of clinical characteristics of the patients in the two cohort: in the treatment of hypertension on the background of type 2 diabetes using standard Protocol (beta-blockers, ACE inhibitors, calcium antagonists, inhibitors of angiotensin II receptor, etc., hypoglycemic agents) and in the presence of coronary heart disease (nitrates, statins, cardioprotective agents) and the Protocol with the addition to the standard treatment of the drug on the basis of coenzyme Q10. These data suggest that the clinical effect was achieved in patients receiving the drug "Qudesan" significantly positively changed the psychological status of patients - decreased symptoms of depression on the scale of specialized questionnaires (tab. 2). In patients treated with "Qudesan", also observed positive clinical effect: a significant decrease in systolic and diastolic blood pressure�, significant reduction of variability in blood pressure, a significant decrease of glucose level and glycosylated hemoglobin, a significant increase of Mg level in the blood, a decrease in total cholesterol, LDL, triglyceride levels, a slight increase in HDL and To the disappearance of signs of ischemia on ECG data, the disappearance of diastolic dysfunction according to Echocardiography. Assessing the impact of the drug on the basis of CoQ10 was performed by comparison of clinical characteristics after treatment. Before treatment compared clinical data were identical, as evidenced by the lack of statistically significant differences between them (p>0,01) (tab. 1).

The study revealed new evidence that the inclusion of a standard Protocol for the treatment of arterial hypertension on the background of diabetes mellitus type 2 drug that contains coenzyme 010, has a positive clinical effect, in particular, consisting in a significant reduction in systolic and diastolic blood pressure, significant reduction in the variability of blood pressure, a significant decrease of glucose level and glycosylated hemoglobin, a significant increase of Mg level in the blood. Also observed a positive effect of combined therapy on reducing anxiety and depression in patients with arterial hypertension on the background of type 2 diabetes.

The use of p�americasa scale (HADS questionnaire and questionnaire CES-D) allows you to assess the level of anxiety and depression in patients with inadequate control of blood pressure and to reveal the peculiarities of their mental status, what should you consider in an integrated approach to treatment tactics of patients is very important in clinical practice.

Surveyed patients characterization of psychological status was conducted twice: at the beginning of the study, the first patient treatment and after 1 year. The duration of treatment due to the fact that this period was sufficient to stabilize blood pressure and variability, as well as to achieve the clinical effect of the drug "Qudesan".

Epidemiology of arterial hypertension in patients with diabetes mellitus currently in the world more than 135 million people suffer from diabetes mellitus (DM). While by 2025 it is projected that the number of such patients will increase in 2 times. Diabetes is a major independent risk factors for cardiovascular morbidity [2, 8]. As you know, most patients with diabetes die from cardiovascular complications, the frequency of which increases sharply in this category. Arterial hypertension (AH) is found in more than 50% of patients with diabetes mellitus, especially type 2 diabetes [5], and is a risk factor for coronary heart disease, acute myocardial infarction, heart rhythm disorders, cardiovascular disease [11]. The prevalence of hypertension in diabetic patients is 1.5-3 times higher compared�Yu with similar age groups of persons not suffering from diabetes mellitus [16]. The development of hypertension and clinical symptoms differ in DM type 1 and type 2. In diabetes mellitus type 1 hypertension develops after a few years with the onset of the disease and usually reflects the severity of diabetic retinopathy. Usually hypertension occurs in 30% of patients with type 1 diabetes [4, 7]. In type 2 diabetes hypertension can occur at the time of diagnosis of the disease or even before the development of hyperglycemia [14]. There are a number of factors complicating the study of the frequency of hypertension in type 2 diabetes: that older age and more severe the degree of obesity compared with patients without diabetes. The prevalence of hypertension in Western countries increases with increasing age and degree of obesity [5, 16]. After adjusting for age and weight, the prevalence of hypertension in DM is still 1.5 times higher than that in those without diabetes [4, 12]. In type 2 diabetes hypertension occurs in 20-60% of patients, varying depending on age, ethnicity, body mass. In some ethnic groups, such as certain Indian tribes, diabetic nephropathy can be the first manifestation of type 2 DM [19]. In some populations revealed "endemic", the existence of hypertension, reduced glucose tolerance or even overt diabetes mellitus type 2, hyperlipidemia, Central type obesity and insulin resistance [15]. Intensive epidemiological studies indicate means�Sal increased risk of cardiovascular complications, renal failure and diabetic retinopathy in DM [11]. The relationship between diabetic neuropathy and hypertension less studied, although it is assumed that AG may be a causal factor in the development of this complication [5, 9]. According to Framingham study, hypertension is 5 times increases mortality among patients with diabetes mellitus [17]. Increases significantly the number of cases of lesions of the lower limbs with the outcome in diabetic gangrene with subsequent amputation. AG leads to the progression of nephropathy and retinopathy, premature disability and death in these patients of chronic renal insufficiency. Hypertension also contributes to the development of diabetic retinopathy, the leading cause of blindness in the U.S. [19]. According to some researchers 35-75% of complications of diabetes, cardio-vascular or kidney may be associated with hypertension [17, 18]. Hypertension is observed in people suffering from diabetes, in 2 times more often than other groups of people [7]. Important in the development of both diseases are lifestyle and heredity. Based on these considerations, hypertension and diabetes as early as possible should be diagnosed and actively treated. Hypertension remains a serious problem for most countries, therefore, the formation of risk groups of patients with diabetes mellitus with hypertension and lipeng� exchange in the initial stages of vascular lesions is extremely important for practical public health for the purpose of rehabilitation, prevent the development of angiopathy and improve the quality of life of patients with diabetes mellitus. The incidence of diabetes and hypertension increases with age among residents of economically developed countries. Most patients with type 2 diabetes constituting 90% of persons with diabetes and hypertension, noted essential hypertension [5, 13].

The variety of ways that could increase the effectiveness of treatment of high blood pressure to diabetes mellitus type 2, must also lie in the sphere of influence on systemic manifestations of the disease, in particular, at reducing depressive and anxiety States.

Thus, the proposed method allows in clinical practice to conduct effective correction of high levels of anxiety and depression in patients with arterial hypertension on the background of diabetes mellitus type 2. In turn, timely medical correction of this important systemic manifestations GB sposobnosti its progression by reducing psychosomatic effects and give patients the opportunity to increase daily physical activity and adherence to treatment.

A list of sources of information

1. Andryushchenko A. V. Comparative evaluation scales CES-D, BDI and HADS in the diagnosis of depression in General practice / V. A. Andryushchenko, M. D. Drobizhev, A. V. Dobrovolsky. // Journal of neurology and PS�hiatari them. S. S. Korsakov. 2003. - No. 5. - P. 11-18.

2. Boytsov S. A. Study of the pathogenesis of hypertension continues // Ter. arch. - 2006. - No. 9. - S. 5-12.

3. All-Russian scientific society of cardiology (GFCF). Diagnosis and treatment of hypertension. Russian recommendations (fourth revision). Systemic hypertension 2010; 35-26.

4. Dedov I. I., Shestakova M. V. diabetes mellitus. - M: Medical information Agency, 2005. - S. 677.

5. Kobalava J. D., Kotovskaya Y., Liskova L. A., Moiseev B. C. the testing and Treatment of elderly patients with arterial hypertension: the representation of doctors and actual practice (according to the Russian scientific-practical program ARGUS). Hypertension 2002; 8:165-168.

6. Koshansky A. G. the relationship of psychological and clinical characteristics in patients with diabetes mellitus type 2 in all its different currents: author. dis. Cand. psychol. Sciences: 19.00.04 / A. G. Koshansky. - SPb., 2007. - 22 p.

7. Sliver V. B., Chazova I. E. cardiovascular complications of diabetes mellitus type 2 // Consilium Medicum. - 2003. - Vol. 5, No. 11. Pp. 504-509.

8. Oganov R. G., Maslennikova G. J. // Cardiology. - 2007. - No. 1. - Pp. 4-7.

9. American Diabetes Association. Treatment of Hypertension in Adults With Diabetes II Diabetes Care. - 2004. - Vol. 27 (Suppl.l). - S65-S67.

10. Association of comorbid depression, anxiety, and stress disorders with Type 2 diabetes in Bahrain, a country with a very high prevalence of Type 2 diabetes / Almawi W., H. Tamim [et al.] // J. Endocrinol. Invest. 31. - 2008. - P. 1020-1024.

11. Blood Presure Lowering Treatment Trialist's Collaboration: Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomized trials // Lancet. - 2000. - Vol. 356. - P. 1945 - 1954.

12. Casey R. G., Gang C, Joyce M., Bouchier-Hayes D. J. Taurine attenuates acute hyperglycaemia such-induced endothelial cell apoptosis, leucocyte-endothelial cell interactions and cardiac dysfunction // J Vase Res. 2007. 44: 31-39.

13. Creates a Vicious Circle Promoting Obesity // Endocrinology. 2006. 147: 3276-3284.

14. Das-Munshi, J. Diabetes, common mental disorders, and disability: findings from the UK National Psychiatric Morbidity Survey / J. Das-Munshi, R. Stewart, K. Ismail, et al. // Psychosom Med. 2007. - Jul-Aug. -69(6): 543-550.

15. Detecting psychological distress in cancer patients: validity of the Italian version of the Hospital Anxiety and Depression Scale. Costantini M, Musso M, Viterbori P, Bonci F, Del ML, Garrone O, et al //. - 1999. - Vol. 7, Ν 3. - P. 121-127.

16. Haffner SM. Obesity and the metabolic syndrome: the San Antonio Heart Study. Br J Nutr 2000; 83 (suppl. 1): 20-70.

17. How do patients with type 2 diabetes perceive their disease? Insights from the French DIA - BASIS survey / H. Mosnier-Pudar, G. Hochberg [et al.] // Diabetes Metab. - 2009. - Vol. 35. - Issue 3. - P. 220-227.

18. Leonardi-Bee, J., Bath P., Phillips S. J., Sandercock P. Blood pressure and clinical outcomes in the International Stroke Trial // Stroke. - 2002. - Vol. 33. - P. 1315-1320.

19. Pennathur s, Heinecke J. W. Oxidative stress and endothelial dysfunction in vascular disease // Curr Diab Rep. 2007. 7: 257-264.

Method of correction of the raised levels of anxiety and depression in patients with arterial hypertension on the background of diabetes mellitus type 2, characterized in that it further on the background of standard pharmacotherapy administered drug "Qudesan" in a dose of 60 mg per day for two months.



 

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EFFECT: obtained is novel mixture of isomers, demonstrating hypotensive activity.

2 cl, 4 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to heterocyclic compound of formula or to its pharmaceutically acceptable salt, where Alk represents linear C1-6 alkylene group, branched C1-6 alkylene group or C1-6 alkylene group, which has ring structure, where part of carbon atoms, constituting ring structure can be optionally substituted with oxygen atom, in ring X, X1 represents N or CRX1, X2 represents N or CRX2, X3 represents CRX3, X4 represents N or CRX4, where RX1, RX2, RX3 and RX4 each independently represents hydrogen atom; linear or branched C1-6alkyl group; linear or branched C1-6alcoxygroup; or halogen atom, in ring Y, Y1 represents CRY1, Y2 represents N or CRY2, Y3 represents N or CRY3, Y4 represents N or CRY4, RY1, RY2, RY3 and RY4 each independently represents hydrogen atom; linear or branched C1-6alkyl group, which can be substituted with halogen atom(s); C3-7alkyl group, which has ring structure; linear or branched C1-6alkoxygroup; halogen atom or cyanogroup, in ring Z, RZ represents linear or branched C1-6alkyl group, which can be substituted with halogen atom(s), or C3-7alkyl group, which has ring structure, which can be substituted with halogen atom(s). Invention also relates to particular compounds, DGAT1 inhibitor based on formula (I) compound, application of formula (I) compound, method of prevention or treatment of diseases, mediated by DGAT1 inhibition.

EFFECT: obtained are novel compounds, possessing useful biological activity.

19 cl, 19 tbl, 149 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to substituted isoquinolines and isoquinolinones of formula (I) and to their stereoisomer and/or tautomer forms and/or pharmaceutically acceptable salts, wherein R1 is H, OH or NH2; R3 is H; R4 is H, halogen or (C1-C6)alkylene-R'; R5 is H, halogen, (C1-C6)alkyl; R7 is H, halogen, (C1-C6)alkyl, O-(C1-C6)alkyl; R8 is H; R6 is absent; or is one of (C1-C4)alkylene related to a cycloalkyl ring related to a cycloalkyl ring, wherein (C1-C4)alkylene forms a second bond to another carbon atom of the cycloalkyl ring to form a bicyclic ring system, R10 is H, phenyl, or pyridine, wherein phenyl is unsubstituted or substituted; R11 is H, (C1-C6)alkyl; or R11 and R12 together with the carbon atom to which they are attached form (C3)cycloalkyl; R12 is (C1-C6)alkyl, (C3-C8)cycloalkyl or phenyl; or R12 is H, provided r=2 and another R12 is other than H; or R11 and R12 together with the carbon atom to which they are attached form (C3)cycloalkyl; R13 and R14 are independently H, (C1-C6)alkyl, (C1-C6)alkylene-R', C(O)O-(C1-C6)alkyl, n is equal to 0; m is equal to 1 or 2; s is equal to 1 or 2; r is equal to 1 or 2; L is O, NH; R' is (C3-C8)cycloalkyl, (C6-C10)aryl; wherein in R11 and R12 residues, alkyl is unsubstituted or optionally substituted by one OCH3; wherein in R11 and R12 residues, alkyl is unsubstituted or optionally substituted by one or more halogens; wherein in R10 and R12 residues, (C6-C10)aryl is unsubstituted or optionally substituted by one or two groups optionally specified in halogen, CN, (C1-C6)alkyl, O-(C1-C6)alkyl, SO2-(C1-C6)alkyl, CF3 and OCF3. Also, the invention refers to using a compound of formula (I).

EFFECT: there are prepared new isoquinoline and isoquinolinone derivatives effective in treating and preventing the diseases related to Rho-kinase inhibition.

38 cl, 132 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to phenol derivatives of formula (1), wherein R1 represents C1-C6 alkyl group, C1-C6 alkynyl group, C1-C6 halogen alkyl group, C1-C6 alkyl sulphanyl group or a halogen atom, R2 represents a cyano group or a halogen atom, R3 represents a hydrogen atom, and X represents -S(=O)2. Besides, the invention refers to a drug preparation containing a compound of formula (I) as an active ingredient.

EFFECT: phenol derivatives of formula (1) characterised by the high urine concentration of the permanent compound, and possess the uricosuric action.

11 cl, 1 dwg, 2 tbl, 42 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to methods of treating type 2 diabetes, insulin resistance, insulin hyposecretion, obesity, hyperglycaemia and hyperinsulinemia, involving administering an effective amount of an anti-IL-1β antibody or its fragment into an individual, as well as to using the anti-IL-1β antibody or its fragment in preparing a composition applicable for treating the above diseases or conditions.

EFFECT: group of inventions is effective in treating type 2 diabetes mellitus, insulin resistance, insulin hyposecretion, obesity, hyperglycaemia and hyperinsulinemia.

67 cl, 13 dwg, 5 tbl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel N-containing heteroaryl derivatives of formula I or II or their pharmaceutically acceptable salts, which possess properties of JAK kinase, in particular JAK3, and can be applied for treating such diseases as asthma and chronic obstructive pulmonary disease (COPD). In formulae A represents carbon and B represents nitrogen or A represents nitrogen and B represents carbon; W represents CH or N; R1 and R2, independently represent hydrogen, C1-4alkyl, halogenC1-4alkyl, -CN; R3 represents C1-4alkyl, R9-C1-4alkyl, Cy1, where Cy1 is optionally substituted with one or several substituents R10; R4 represents hydrogen, C1-4alkyl, R12R7N-C0alkyl, where one of R7 and R12 represents hydrogen, and the other represents C1-4alkyl or group R13, which is selected from C1-5alkyl, Cy2-C0alkyl; R5 represents hydrogen; R6 represents hydrogen, C1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkyl, R12R7N-C1-4alkyl, R16CO-C0alkyl, Cy1; R7 represents hydrogen or C1-4alkyl; R9 represents halogen, -CN, -CONR7R12, -COR13, CO2R12, -OR12, -SO2R13, -SO2NR7R12, -NR7R12, -NR7COR12; R10 represents C1-4alkyl or R9-C0-4alkyl; R11 represents C1-4alkyl, halogen, -CN, -NR7R14; R12 represents hydrogen or R13; R13 represents C1-5alkyl, hydroxyC1-4alkyl, cyanoC1-4alkyl, Cy2-C0alkyl or R14R7N-C1-4alkyl; where Cy2 is optionally substituted with one or several constituents R11; R14 represents hydrogen or C1-4alkyl; R16 represents C1-4alkyl, halogenC1-4alkyl, C1-4alkoxyC1-4alkyl, hydroxyC1-4alkyl or cyanoC1-4alkyl; Cy1 represents monocyclic carbocyclic unsaturated or saturated ring, selected from C3-C6cycloalkyl, phenyl, or saturated monocyclic 4-6-membered heterocyclic ring, containing from 1 to 2 heteroatoms, selected from N and S, or partially unsaturated 10-membered bicyclic heterocyclic ring, containing oxygen atom as heteroatom, which can be substituted with group R11, where said ring is bound with the remaining part of molecule via any available C atom, and where one or several ring C or S atoms are optionally oxidised with formation of CO or SO2; and Cy2 represents monocyclic carbocyclic unsaturated ring, selected from C3-C6cycloalkyl, or aromatic monocyclic 4-6-membered heterocyclic ring, containing from 1 to 2 heteroatoms, selected from N and S, or unsaturated 10-membered bicyclic heterocyclic ring, containing oxygen atom as heteroatom, which can be substituted with group R11, where said ring is bound with the remaining part of molecule via any available atom C or N.

EFFECT: obtaining novel heteroaryl derivatives.

27 cl, 41 ex

Transdermal plaster // 2553350

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine. Described is matrix layer, suitable for application in plaster for transdermal delivery, aimed at introduction of biologically active compounds, which includes phosphate compound of tocopherol and polymer carrier. Also described is transdermal plaster and method of its production.

EFFECT: plaster makes it possible to efficiency introduce biologically active compounds.

48 cl, 15 tbl, 13 dwg, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry and represents clinical nutrition for prevention, treatment or relief of one or several symptoms, associated with impairment of metabolism or its disorder, which contains composition of polysaccharide high-viscosity dietary fibre, including viscous fibre mixture or its complex, consisting of from 48% to 90% in wt % of glucomannan, from 5 to 20 % in wt % of xanthan gum and from 5% to 30% in wt % of alginate, as well as, at least, one macroelement, selected from the group, consisting of protein carbohydrate and fat, where clinical nutrition is composed in order to provide dose of composition of polysaccharide high-viscosity dietary fibre from 20 g/day to 35 g/day for time period, effective for prevention, treatment and relief of one or several symptoms, associated with impairment of metabolism or its disorder.

EFFECT: invention ensures extension of arsenal of means, preventing, relieving or treating one or several symptoms, associated with impairment of metabolism or metabolic disease.

14 cl, 6 ex, 20 tbl, 48 dwg

FIELD: medicine.

SUBSTANCE: patients with diabetic microangiopathy are subjected to an examination which includes: general blood test, blood sugar, general urine analysis, ultrasonic examination of kidneys with the determination of indices of the kidney blood flow (Vmax, Vmin, S/D, PI, RI), basic ophthalmological parameters (vision acuity, examination of eye fundus vessels). Then, the intake of mildly-mineralised hydrocarbonate-chloride-sodium mineral water "Obyhovskaya" directly from the spring under sanatorium conditions is administered. Water is taken in heated to a temperature of 37°C in a dose of 3 ml per 1 kg of body weight 3 times per day 40 minutes before meal, the course constitutes 18 days.

EFFECT: application of the invention makes it possible to normalise the general blood test, blood sugar, general urine analysis, improve the condition of the visual analyser and indices of the kidney blood flow.

1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to 2-pyridone compounds, represented by general formula [1], , where A represents benzene ring or pyridine ring, X represents structure, represented by general formula [3], V represents single bond or lower alkylene, W represents single bond, ether bond or lower alkylene, which can include ether bond, or their tautomers or stereoisomers.

EFFECT: obtaining pharmaceutically acceptable salts, which possess excellent activating activity with respect to GK and can be applied as medications.

27 cl, 23 tbl, 371 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to quinolines substituted by phosphorus-containing group of formula and applicable in medicine, wherein Z represents V1 and V2 are independently specified in hydrogen or halogen; one of R and R` represent phosphorus-containing substitute Q; the other one is specified in hydrogen or methoxyl; wherein the phosphorus-containing substitute Q represents A represents O; L represents C1-6alkyl; J represents NH or C3-6heterocycloalkyl and J is optionally substituted by G3; X is absent or represents -C(=O)-; X is absent or represents C1-6alkyl; each of R1 and R2 are independently specified in C1-6alkyl or C1-6alkoxy; G3 represents C1-6alkyl, R3S(=O)m-, R5C(=O)- or R3R4NC(=O)-; R3, R4 and R5 are independently specified in 3 or C1-6alkyl; m is equal to 0-2.

EFFECT: there are presented new protein kinase inhibitors effective for treating the diseases associated with abnormal protein kinase activity.

20 cl, 42 ex, 8 tbl, 3 dwg

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to endocrinology, and deals with stimulation of insulin secretion. For this purpose 2 ml of concentrated nitro-glycerine solution are diluted with distilled water, cotton swab is soaked with obtained solution, stretched to 10-12 cm long and 3-4 cm wide size, applied perpendicular to spine on the left at the level of Th12, covered with cellophane and sealed with self-adhering plaster, with patient being turned onto back with preservation of said position for 1 hour.

EFFECT: method provides enhancement of insulin secretion by pancreas due to improvement of its blood supply.

2 ex, 2 tbl, 4 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to new substituted aminotetrahydropyranes of structural formula or to their pharmaceutically acceptable salts , and , wherein V is specified in groups having the formulas below, Ar represents phenyl unsubstituted or substituted by one to five halogen atoms, each of R1 and R2 is independently specified in C1-C6alkyl; R3 is specified in a group consisting of C1-C6alkyl; cyano; tetrazolyl; -C(O)OC1-C6alkyl and -C(O)NH2; wherein C1-C6alkyl is substituted by 1-4 substitutes independently specified in a group consisting of OH; -C(O)NH2 and -CO2H. The declared compounds can be dipeptidylpeptidase-IV inhibitors and can be applicable in treating or preventing diseases involving the enzyme dipeptidylpeptidase-IV, such as diabetes, and especially type 2 diabetes mellitus.

EFFECT: invention also refers to a pharmaceutical composition containing the above compounds, and using the above compounds and compositions for preventing or treating the diseases involving the enzyme dipeptidylpeptidase-IV.

12 cl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the field of organic chemistry, namely to derivatives of diaza-spiro[4.5]decan-1-one of formula (I) or to their pharmaceutically acceptable salts, where. R1 is a substituted phenyl, which contains one substituent, selected from the group, including C1-4-alkyl, C3-6-cycloalkyl halo-C1-4-alkyl and halo -C1-4-alkoxy, and which can additionally contain one substituent, selected from a halogen; R2 is hydrogen, C1-4-alkyl, phenyl, substituted phenyl, with the substituted phenyl containing one substituent, selected from the group, including C1-4-alkoxy; R3 is -R4, -C(OH)R5R6 or -C(O)NR7R8; R4 is phenyl, phenyl-C1-4-alkyl, substituted phenyl, substituted phenylcarbonyl, with the substituted phenyl, substituted phenylcarbonyl containing from one to two substituents, selected from the group, including a halogen, halo-C1-4-alkyl; one of R5 and R6 is hydrogen, C1-4-alkyl, and the other is aminocarbonyl, phenyl, substituted phenyl or substituted phenyl-C1-4-alkyl, with the substituted phenyl or substituted phenyl-C1-4-alkyl containing from one to two substituents, independently selected from the group, including a halogen; one of R7 and R8 is hydrogen C1-4-alkyl, and the other is C1-4-alkyl, C3-6-cycloalkyl, C1-4-alkoxy-C1-4-alkyl, phenyl-C1-4-alkyl, substituted phenyl or substituted phenyl-C1-4-alkyl, with the substituted phenyl or substituted phenyl-C1-4-alkyl containing one substituent, selected from the group, including a halogen, halo-C1-4-alkyl; or R7 and R8 together with a nitrogen atom, which they are bound to, form pyrrolidinyl; n equals zero or 1/ The invention also relates to a pharmaceutical composition based on the compound of formula (I), application of the formula (I) compound and a method of treatment.

EFFECT: obtained are novel heterocyclic compounds, useful as an inhibitor of hormone-sensitive lipase.

17 cl, 57 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds of formula I, possessing ability of binding with delta-opioid receptors. In formula R1 is selected from the group, consisting of i) phenyl, optionally substituted with one-two substituents, independently selected from the group, consisting of C1-4alkyl, C1-4alcoxy, C1-4alkylthio, hydroxyl, di(C1-4alkyl), aminocarbonyl, chlorine and fluorine, in such a way that only one di(C1-4alkyl)aminocarbonyl is present; ii) naphthyl; iii) pyridinyl, optionally substituted with one substituent, selected from the group, consisting of C1-4alkyl, C1-4alcoxy, C1-4alkylthio, hydroxy, fluorine, chlorine and cyano; iv) pyrimidin-5-yl; v) furanyl; vi) thienyl; vii) 5-oxo-4,5-dihydro-[1,2,4]oxodiazol-3-yl; and viii) di(C1-2alkyl)aminocarbonyl; Y represents ethyl, vinyl or bond; or Y represents O, when R1 represents optionally substituted phenyl, where substituent represents C1-4alcoxy; R2 represents phenyl, optionally substituted with one-two substituents, independently selected from the group, consisting of C1-4alkyl, C1-4alcoxy, fluorine, chlorine and cyano, trifluoromethoxy and hydroxy; or R2 represents phenyl, substituted with one aminocarbonyl, di(C1-4alkyl)aminocarbonyl, C1-4alcoxycarbonyl or carboxysubstituent; R3 is selected from the group, consisting of i) 3-aminocyclohexyl; ii) 4-aminocyclohexyl; iii) piperidin-3-yl; iv) piperidin-4-yl; v) pyrrolodin-2-yl-methyl, in which pyrrolodin-2-yl is optionally substituted by 3-rd or 4-th position with one or two fluorine-substituents; vi) azetidin-3-yl; vii) 2-(N-methylamino)ethyl; viii) 3-hydroxy-2-aminopropyl; ix) piperidin-3-yl-methyl; x) 1-azabicyclo[2.2.2]octan-3-yl; and xi) 8-azabicyclo[3.2.1]octan-3-yl; or R3 together with Ra and nitrogen atom, which they both are bound to, form piperazinyl, optionally substituted with 4-C1-4alkyl; Ra represents hydrogen, 2-(N-methylamino)ethyl or C1-2alkyl, optionally substituted with azetidin-3-yl.

EFFECT: compounds can be used in treatment of pain in the range from medium to strong, caused by diseases or conditions, such as osteoarthritis, migraine, burn, fibromyalgia, cystitis, rhenite, neuropathic pain, idiopathic neuralgia, toothache, etc.

21 cl, 4 tbl, 26 ex

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