Method for correcting cognitive disorders in patients with arterial hypertension accompanying type 2 diabetes mellitus

FIELD: medicine.

SUBSTANCE: correcting cognitive disorders in the patients suffering arterial hypertension accompanying type 2 diabetes mellitus is ensured by combining a standard drug therapy with administering the preparation Kudesan 60 mg a day throughout two months.

EFFECT: administering Kudesan in the above dose and regimen provides the effective correction of cognitive disorders in the above group of patients in a combination with improving the cardiovascular function and metabolic processes.

2 tbl, 1 ex

 

The invention relates to medicine, internal medicine, specifically to methods of correction of cognitive impairment (KN) in patients with essential hypertension on the background of diabetes mellitus (DM) type 2.

To date, there is compelling evidence that chronic hyperglycemia causes damage to the Central nervous system. Cerebral complications of DM as the 1st and 2nd types can be designated by the term "diabetic encephalopathy" - this concept was proposed by E. Rescke and Nielsen in 1965 [15]. Since then, there has been a considerable number of works, mostly relevant and comparative, at least - a prospective and longitudinal. The qualitative features of cognitive disorders in diabetes mellitus, the relationship between clinical characteristics of diabetes and the assessment of cognitive functions, neurophysiological and neurochemical basis of disorders of higher cerebral function in diabetes mellitus [19, 22]. However, to this day there remain many open questions related to phenomenology, pathogenesis diagnosis of cognitive impairment (KN) in DM. More attention to the problem in DM KN has received in recent years in connection with the detected connection of diabetes with the incidence of Alzheimer's disease (AD) [10].

Data on the prevalence KN among DM patients in the literature a bit. Most authors agree that the Board of Directors Pref�leads mainly to the lungs and moderately impaired cognitive function, dementia is less common [5, 22].

According to a study conducted in the USA, the prevalence of moderate CI (MCI) in DM 2nd type is 20% among men and 18% among women 60 years and older [19], which is slightly greater than the prevalence of MCI in the General population (10-15%) [15]. Bruce D. G et al. found that only 36% of patients with type 2 diabetes do not have the cognitive and emotional disorders [10]. Meanwhile, even a small reduction of cognitive functions in diabetic patients may lead to deterioration of metabolic control and, therefore, more rapid development of diabetic complications and disability [7, 19].

Determining the severity of the disorders is the basis of modern classification of cognitive impairment, which can be divided into mild, moderate, or severe dementia). Of special interest at the present time is called early forms of cerebral dysfunction known as mild cognitive disorders - UKR (mild cognitive impairment), not reaching the degree of dementia. This term (mild cognitive impairment - MCI) was first proposed in 1997 by American neurologist B. Petersen to refer predementia stages of Alzheimer's disease. The specified syndrome characterized by the prevalence of subjective disorders (memory loss, mental health) that over a sufficiently long period of time can be compensated[15]. In addition, it is light and mild cognitive impairment perspective from the point of view of the effectiveness of therapeutic interventions and prognosis. Although mild cognitive impairment is so severe socio-economic and emotional burden of dementia, however, the presence of even mild cognitive disorders significantly reduces the patient's quality of life, the ability to effectively perform the recommended treatment of any comorbidities [12]. Mild cognitive impairment is associated with significant risk of subsequent development of dementia and severe disability [18]. The prevalence of the syndrome UKR among older persons actively studied. However, despite the high prevalence of cognitive impairment 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 cognitive impairment. Regional aspects of cognitive impairment, risk factors for cardiovascular disease (CVD), their interaction has not been studied.

A study of patent and scientific and medical information sources did not reveal the methods of correction to�naivnyh disorders in patients with arterial hypertension on the background of type 2 diabetes.

A new technical task is the creation of ways in clinical practice to conduct a significantly positive drug correction of cognitive impairment.

To solve the problem in the way of correction of cognitive impairment in patients with essential hypertension on the background of diabetes mellitus (DM) type 2 are additionally on the background of traditional pharmacotherapy administered drug "Qudesan" in a dosage of 60 mg per day for two months.

The method is as follows. At the outpatient stage at the first visit carried out complex of measures, including medical history 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. Also carried out 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, filling medical scales for special purposes. Use the rating scale mental status MINI-MENTAL STATE EXAMINATION (MMSE) [1]. M. F. FOLSTEIN, S.E. FOLSTEIN, P. R. HUGH. 1975. The test result obtained by the summation of scores on each item.

Maximum display�tel Aviv in this test - 30 points, which corresponds to the highest cognitive abilities. The lower the test result, the more pronounced cognitive deficits. Evaluation results on a scale MMSE is performed respectively to the total points:

28-30 points - Norm. Cognitive impairment is missing.

24-27 points - Cognitive impairment.

20-23 points - Dementia mild degree.

11-19 points - Dementia of moderate severity.

0-10 points - Severe dementia.

In identifying cognitive impairment patients in addition to standard Protocol of treatment of hypertension on the background of type 2 diabetes on a background of standard drug therapy, including beta-blockers, ACE inhibitors, calcium antagonists, inhibitors of angiotensin II receptor, etc., hypoglycemic agents and in the presence of ischemic heart disease, respectively, nitrates, statins, cardioprotective funds administered mitochondrially coenzyme CoQ10 - drug "Qudesan" on 60 mg a day for two months.

The proposed method of correction of cognitive impairment in patients with arterial hypertension on the background of diabetes mellitus type 2 is illustrated with a concrete example.

Example 1. Patient 3., the woman, 58 years old, retired. Is registered with a General practitioner with a diagnosis of coronary artery disease: SP FC II. Hypertension stage III, the achieved degree of AH 1, the risk 4. Sugar d�abet type 2, the target level of HbA1c < 7,5%. Is on standard therapy of hypertension and DM. From history: hypertension affects about 20 years, diabetes mellitus 7 years, ischemic heart disease for about two years. Complained of increased blood pressure to 165/130 mm Hg.CT., headaches, occasionally during exercise shortness of breath Taking enalapril 10 mg per day, losap 100 mg, 1 so - 2 times a day., maninil 3,5 mg t - 2 times a day., diabeton MB 1 so - 2 times per day. Drugs taking constantly. Objectively: the condition is satisfactory, vesicular breathing, no rales, heart sounds clear, rhythmic, HELL 147/110 mm Hg.PT. total blood leukocytes of 4.4×109/l; erythrocytes - 4,9×1012/l; hemoglobin - 138 g/l; platelets - 305×109/%; ESR - 2 mm/hour. Biochemical analysis blood glucose was 7.1 mmol/l; glycosylated hemoglobin is 6.32 per cent; cholesterol of 5.0 mmol/l; triglycerides was 1.47 mmol/l; LDL - 3.9 mmol/l; HDL - 1.6 mmol/l; PETIT 99,1%; APTT - 29 sec; fibrinogen - 3.22 g/l; Potassium - 4,01 mmol/l; Magnesium - 0,68. Urinalysis: color - yellow, transparent, density 1015, protein is not specified, sugar - not determined; microscopy: leukocytes 0-1-0, erythrocytes 0-1 in the field of view. Conclusion: hyperglycemia. ECG: sinus rhythm, right, HR - 70 in 1 minute, the deviation of the EOS left, signs of left ventricular hypertrophy, signs of myocardial ischemia. Echocardiography: heart Chambers are not dilated. Akratitos�ü left and right ventricles are normal. Violation of local contractility (alone) no. Diastolic dysfunction (impaired relaxation). Concentric left ventricular hypertrophy. Valves without modification, are functioning normally. Pericardium - without features. The patient on the background of standard therapy, was appointed Qudesan drug at a dose of 60 mg per day for two months. According to the proposed method before treatment were identified cognitive impairment on the MMSE scale - 26 points, which corresponds to the presence of cognitive impairment. After one year of follow-up examination was repeated. Objectively: the condition is satisfactory, vesicular breathing, no rales, heart sounds clear, rhythmic, BP 125/90 mmHg.PT. General analysis of blood leukocytes to 4.2×109/l; erythrocytes - 4,9×1012/l; hemoglobin - 139 g/l; platelets - 297×109/%; ESR - 3 mm/hour. Biochemical analysis of blood: glucose - 5,8 mmol/l; glycosylated hemoglobin - 5,01%; cholesterol is 4.03 mmol/l; triglycerides - 1,42 mmol/l; LDL - 3.0 mmol/l; HDL - 1.8 mmol/l; PETIT 96,4%; APTT - 30 sec; fibrinogen - 3,16 g/l; Potassium 4.5 mmol/l; Magnesium - 0,96. Urinalysis: color - yellow, transparent, density 1013, protein is not specified, sugar - not determined; microscopy: leukocytes 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, great�ilen, HR - 69 in 1 minute, the deviation of the EOS to the left, the signs of hypertrophy of the left ventricle. Echocardiography: heart Chambers are not dilated. The contractility of the left and right ventricles are normal. Violation of local contractility (alone) no. Diastolic left ventricular function is not impaired. Concentric left ventricular hypertrophy. Valves without modification, are functioning normally. Pericardium - without features. Determination of cognitive impairment on the MMSE scale -30 points, which corresponds to the norm. Obtained data allow to conclude that 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 60 mg a day for two months has a significant positive effect on the characteristics of cognitive functions of the patient, clinical features, laboratory and instrumental studies

The proposed method 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 nom�R No. LSR-003092/10, Trade name: "Qudesan", rational Chemical 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 (cremophor 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: CEW

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 damage zone miokarda 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.

Pharmakinetic: Data about the pharmacokinetics of the drug is not provided.

Indications for use:

Adults:

For prevention and complex therapy of different 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:

-asthenic syndrome;

- the recovery period after a serious illness and surgery.

Adults and children older than 1 year:

- to prevent and compensate for a deficiency of coenzyme Q10;

- to improve adaptation to increased physical activity in athletes.

Contraindications:

- children up to age 1 year;

- hypersensitivity to the drug components.

The way of application and dose:

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 claimed indications in accordance with the recommendations of the

The duration of application of PR�ttings Qudesan is 2-3 months. Repeated courses on the recommendation of a doctor.

Side effects: From the digestive system: very rarely - nausea, diarrhea.

Other: possible allergic reactions.

Drug interactions:

Concomitant use of lipid-lowering drugs (statins, fibrates, beta-blockers (atenolol, metoprolol, propranolol), tricyclic antidepressants may result in a decrease in the concentration of ubidecarenone in plasma. Ubidecarenone may potentiate the effect of diltiazem, metoprolol, enalapril and nitrates, as well as to reduce the effect of warfarin.

Overdose: cases of overdose of the drug Qudesan was observed.

Precautions: None.

Product: Drops for oral administration of 3%. 20 ml in bottles of dimming (orange) glass with polyethylene stopper-dropper and screw caps.

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 a rapid boring�th 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, medication, strenuous, violations of metabolism. 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 a support means - drugs 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 complex therapy of cardiovascular diseases. 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 the technology, p�svalivau translate poorly digestible fat-soluble substance Q10 in a water soluble form, optimal for absorption and easy to use. This technology is used in the production of Cudesna. Thanks to water-soluble form of coenzyme Q10, Qudesan able to more effectively compensate for a deficiency of Q10 in the human body.

As a result of a clinical study discovered a new property of the drug on the basis of coenzyme Q10, namely its ability correction of cognitive disorders 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". At the outpatient stage, at the first visit and after 1 year, conducted a range of activities including medical history 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. Conducted biochemical analysis of whole plasma, fasting: we examined the level of glucose, glycosylated hemoglobin, lipid profile (cholesterol, triglycerides, LDL, HDL), indicators of blood coagulation (PI, APTT, fibrinogen), electrolytes (K, Mg). Also patients spend filling out medical scales for special purposes. Used the rating scale mental stat�sa MINI-MENTAL STATE EXAMINATION (MMSE) [1].

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 was defined 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, inhibitors of AP�, 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, the use of drugs unless prescribed by a physician-researcher, 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). Patients�ntam were assigned 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:

In table 1 the data of the dynamics of clinical indicators 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",

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

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

and Table 2 shows the dynamics of clinical indicators 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" presents 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�AI ischemic heart disease (nitrates, statins are cardioprotective means) 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", showed a significant improvement of cognitive functions in patients according to the MMSE scale (tab. 2). In patients receiving "Qudesan", also observed positive clinical effect: there was a significant decrease 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, 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 2 t�PA medicines containing Q10 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 noted the positive influence of therapy on cognitive function in patients with arterial hypertension on the background of type 2 diabetes.

Using the MMSE scale allows an assessment of cognitive functions in patients with inadequate control of blood pressure and reveal their offense, it should be considered in an integrated approach to treatment tactics of patients is very important in clinical practice.

Surveyed patients study of cognitive function was performed 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 predicted that h�a layer of such patients will increase in 2 times. Diabetes is a major independent risk factors for cardiovascular morbidity [2, 91. 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 [6], and is a risk factor for coronary heart disease, acute myocardial infarction, heart rhythm disorders, cardiovascular disease [13]. The prevalence of hypertension in diabetic patients is 1.5-3 times higher compared to the same age groups of persons not suffering from diabetes mellitus [17]. 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 develops in "30% of patients with type 1 diabetes [4, 8]. In type 2 diabetes hypertension can occur at the time of diagnosis of the disease or even before the development of hyperglycemia [4]. 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 [6, 17]. After adjustment for age and�with the prevalence of hypertension in DM is still 1.5 times higher than that in those without diabetes G4, 14]. 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 diabetes [21]. 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 [4, 13]. Intensive epidemiological studies indicate a significant increased risk of cardiovascular complications, renal failure and diabetic retinopathy in DM [13]. 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 [6, 11]. According to Framingham study, hypertension is 5 times increases mortality among patients with diabetes mellitus [18]. 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 main cause of blindness in the U.S. [21]. According to some researchers 35-75% of complications of diabetes, cardio-vascular or kidney may be associated with hypertension [18, 20]. Hypertension is observed in people suffering from diabetes, in 2 times more often than other groups of people [8]. 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 groups at risk diabetic patients with hypertension and lipid metabolism in the initial stages of vascular lesions is extremely important for practical public health for the purpose of rehabilitation, prevention of 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 [6, 16].

The direction of the treatment of hypertension today is facing to stabilize blood pressure, reduce blood pressure variability. The choice of means, which could increase the effectiveness of treatment of high blood�CSOs pressure on the background of diabetes mellitus type 2, must also lie in the sphere of influence on systemic manifestations of the disease, in particular for the improvement of cognitive functions.

Thus, the proposed method allows in clinical practice to conduct effective correction of cognitive impairment in patients with arterial hypertension on the background of diabetes mellitus type 2. Timely medical correction of this important systemic manifestations GB, at least slow its progression by reducing cognitive impairment and will give patients the opportunity to increase daily physical activity and adherence to treatment.

A list of sources of information taken into account when preparing the description

1. Belova A. N. Scales and questionnaires in neurology and neurosurgery. - M., 2004. - 432 p.

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. Zakharov V. V., Yakhno N. N. The syndrome of mild cognitive disorders in the elderly: diagnosis and treatment. Rus. honey. Phys. 2004; 10:573-6.

6. Kobalava J. D., Kotovskaya Y., With�iscove 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.

7. Levin O. S., Golubeva L. V. Heterogeneity moderate cognitive disorders: diagnostic and therapeutic aspects. Consilium Medicum 2006; 12:106-10. Sliver V. B., Chazova I. E. cardiovascular complications of diabetes mellitus type 2 // Consilium Medicum. - 2003. - T. 5, No. 11. - C. 504-509.

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

9. Yakhno N. N. Cognitive disorders in neurological clinic // Neuro. Phys. - 2006; 11 (Appendix 1): 4-12.

10. American Diabetes Association. Treatment of Hypertension in Adults With Diabetes II Diabetes Care. - 2004. - Vol. 27(Suppl. 1). - S65-S67.

11. Birns J, Morris R, Donaldson N, Kaira L. The effects of blood pressure reduction on cognitive function: a review of effects based on pooled data from clinical trials. J Hypertens 2006; 24:1907-14.

12. Blood Pressure 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.

13. Casey R. G., C. Gang, 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.

14. Cox D. J., Kovatchev B. P. fonder-Frederick L. A. et al. Relationships Between Hyperglycemia and Cognitive Performance Among Adults With Type 1 and Type 2 Diabetes//Diabetes Care. l997. Vol. 28. P. 71-77.

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

16. Haffner SM. Obesity and the meabolic 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 DIABASIS survey / H. Mosnier-Pudar, G. Hochberg [et al.] // Diabetes Metab. - 2009. - Vol. 35. - Issue 3. - P. 220-227.

18. Jefferson A, Benjamin E. Cardiovascular disease, cognitive decline and dementia. Vascular cognitive impairment in clinical practice. Eds. L. Wahlung TErkinjuntti, S. Gauthier. Cambridge 2009; 166-77.

19. 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.

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

21. Vogels R, Oosterman J, Harten B. Neuroimaging and correlates of cognitive function among patients with heart fatiure. Dement Geriatr Cogn Disord 2007; 24:418-23.

Method of correction of cognitive impairment 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 dosage of 60 mg per day for two months.



 

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2 cl, 2 ex, 4 tbl, 2 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to therapy and endocrinology, and concerns the correction of the crisis course of hypertensive disease and abdominal obesity. To this effect, Moxogamma 200-400 mcg/day and Reduxin 18-30 mg/day are administered with underlying a therapy of the angiotensin converting enzyme inhibitor lisinopril. The preparations are administered in two stages - in the morning and 6 or 7 hours later; Moxogamma is first to be administered, and Reduxin is administered 40-60 min later.

EFFECT: method provides decreasing systolic and diastolic pressure, reducing the signs of cardiac failure and correcting the metabolic disorders by improving the endothelial function, reducing the sympathetic activity and the insulin resistance.

12 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new cyclic indolysincarboxamides and azaindolysincarboxamides of formulas Ia and Ib:

presented below, wherein the values of R, Ra, R10, R20, R30, R40, Y, n, p and q are specified in cl. 1 of formula. What is described is a method for preparing them.

EFFECT: compounds exhibit rennin-inhibitory activity that enables using them in the pharmaceutical composition and for treating hypertension.

11 cl, 4 tbl, 17 ex

FIELD: pharmacology.

SUBSTANCE: invention relates to a therapeutical or preventive agent for treatment of hypertension or high blood pressure and to the appropriate method of treatment with its usage. The proposed agent contains (a) and (b) as active ingredients: (a) 2-(3-cyano-4-isobutyloxyphenyl)-4-methyl-5-thiazolcarbonic acid (febuxostat) or its pharmaceutically acceptable salt; (b) a compound selected from a group made of blockers of calcium channels, blockers of a receptor of angiotensin II, and inhibitors of an angiotensin-converting ferment and their salts applicable from the point of view of medicine.

EFFECT: synergism of lower blood pressure on a model of spontaneous hypertension.

9 cl, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry, namely to mixture of E- and Z-isomers of (4-bromophenyl)ethylidene hydrazide of 2-[6-methyl-1-(thiethan-3-yl)uracyl-3-yl]acetic acid in molar ratio 3.5:1 of general formula: .

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.

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

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: 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

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