Method for correcting immune disorders in patients with ischemic cardiac and type ii diabetes

FIELD: medicine, cardiology.

SUBSTANCE: the present innovation deals with treating patients with ischemic cardiac disease at the background of type II diabetes. For this purpose, in case of stenocardia of functional class II and type II diabetes of average severity degree one should introduce enalapril at the dosage of 20 mg/d in combination with trental at the dosage of 400 mg/d, and at stenocardia of functional class III and type II diabetes of severe flow one should introduce enalapril at the dosage of 30 mg/d in combination with trental at the dosage of 400 mg/d. The innovation suggested normalizes monocytic-macrophageal link of immune system.

EFFECT: higher efficiency of correction.

2 ex, 4 tbl

 

The invention relates to medicine and immunology, and can be used for correction of immune disorders in patients with ischemic heart disease on the background of diabetes mellitus type 2 (DM).

Closest to the invention is the use of enalapril and pentoxifylline in patients with chronic heart failure to reduce excessive levels of TNFα and IL-6. (Ziu, Zhao SP Changes of circulating tumor necrosis factor levels in patients with congestive heart failure influenced by therapy. Jut. CasrdioL, 1999, 69 (I): 77-82. Skudicky D., et al., Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol: results randomized study. Circulation, 2001, 103 (8): 1083-1088). The described method was applied in patients with chronic heart failure due to dilatational cardiomyopathy. In patients with chronic heart failure therapy with enalapril and pentoxifylline showed decrease in the level of TNFα and IL-6. In the given work the effectiveness of treatment with enalapril and pentoxifylline were evaluated by changing the content of TNFα and IL-6 without taking into account the effect of these drugs on other parts of the immune system that it is not possible to fully assess the activity of the immune correcting action of drugs, the possibility of their use in patients with coronary artery disease on the background of diabetes. The described method does not take into account the differentiated approach to therapy is defined by the dose regimens ven the preparations.

The objective of the invention was to develop a method of immune disorders in patients with ischemic heart disease on the background of diabetes mellitus type 2.

This object is achieved by assigning enalapril (20-30 mg/day) and trental 400 mg/day) and within 3-4 weeks. To assess systemic immunity was studied subpopulation composition of peripheral blood lymphocytes using monoclonal antibodies to the structures of CD4+ (T helper cells), CD8+ (cytotoxic lymphocytes), CD20+ (b cells), CD25+, CD95+, HLA-DR+ (markers of lymphocyte activation). The levels of immunoglobulins G, M was estimated by the method of immunodiffusion, the levels of the cytokines IL-1β, IL-6, TNFα, IL-4, neopterin concentrations, With3With4components of complement was determined by ELISA. All the patients before treatment and after treatment were carried out clinical and laboratory studies, including: determination of immune status, echocardiography, ECG monitoring and cycle ergometry.

Clinical testing of the proposed method was performed in 104 patients with angina II-III functional class against type 2 diabetes moderate and heavy flow, which amounted to 3 groups. All patients received diet and hypoglycemic agents in accordance with the severity of diabetes. Patients of the 1st group, along with the means of glycemic control included microsorb the Dr. 300 mg/day. Therapy patients of the 2nd group consisted of enalapril (20 mg/day) + trental 400 mg/day), the 3rd group - enalapril (30 mg/day) in combination with answered (400 mg/day). Patients of all examined groups on background therapy had positive clinical dynamics: improved health, reduces General weakness, were stopped insipidly syndrome, disappeared attacks of anginal pain, decreased shortness of breath, increased tolerance to physical activity. Positive clinical dynamics was confirmed data ECG monitoring, cycle ergometry (VEM).

In patients with angina II FC and SD moderate after combined treatment with enalapril (20 mg/day) and answered (400 mg/day) along with clinical remission achieved correction of immune disorders. The results of the research of the immune status in this group of patients after treatment showed normalization of the subpopulation composition of lymphocytes, a decrease in their expression of early (CD25+) and late (HLA-DR+) markers of activation, a decrease in the expression of the lymphocyte induction factor apoptosis CD95+ (table 1), the concentration of TNFα, IL-1β, IL-4, IL-6 (table 3), the activity of the complement system (table 4). Decreased content of serum immunoglobulins (table 2). There was also a decrease in the level of blood neopterin concentrations to levels seen in the control group (6,5±0,03 small), testified to normalize the activity of the monocyte-macrophage immunity.

In patients with angina FC III and DM heavy flow of inclusion in therapy of enalapril (30 mg/day) and trental 400 mg/day) along with clinical compensation allowed to achieve an effective immune. During treatment, a marked increase in the content of CD4+, reduction of CD8+ and CD20+ lymphocytes, a decrease in their expression of early (CD25+) and late (HLA-DR+) markers of activation, a decrease in the expression of the lymphocyte induction factor apoptosis CD95+.

To the level of healthy donors decreased the concentration of serum IL-6, IL-4. Significantly decreased the level of TNFα, IL-1βand blood neopterin concentrations (table 2, 3). Control study of immune status in patients of the 1st group (therapy nitrosorbid) significant changes in the activity of inflammation is not found.

10,1±0,8*1,3,5
Table 2
Dynamics of the level of serum immunoglobulins and neopterin concentrations in patients with CHD and DM during therapy
№ p/pThe group surveyedIg G g/lIg M g/lNeopterin nmol/l
1Control (n=37)11,5±0,321,42±0,04 6,2±0,2
Before the treatment
2Patients with angina II FC and SD moderate (n=51)15,3±0,51*12,11±0,05*18,4±0,4*1
3Patients with angina III FC SD and severe (n=53)17,5±0,53*1,22,63±0,09*1,213,8±0,6*1,2
Therapy nitrosorbid
4Patients with angina II FC and SD moderate (n=14)15,1±0,46*12,01±0,07*17,8±0,3*1
5Patients with angina II FC SD and severe (n=14)16,3±0,65*12,55±0,07*112,6±0,7*1,2
Therapy enalapril 20 mg + trental 400 mg
6Patients with angina II FC and SD moderate (n=37)13,1±0,51*1,2,41,51±0,03*2.4GHz6,5±0,3*2.4GHz
Therapy amlodipine 30 mg + trental 400 mg
7Patients with angina III FC SD and severe (n=39)14,8±0,45*1,3,51,87±0,05*1,3,5

Table 3
Dynamics of serum cytokines in patients with CHD and DM depending on therapy.
№ p/pThe group surveyedIL-1β

PCG/ml
IL-6

PCG/ml
TNFα

PCG/ml
IL-4

PCG/ml
1Control (n=37)31,8±5,812,3±1,232,6±4,818,6±1,8
Before the treatment
2Patients with angina II FC and SD moderate (n=51)94,9±5,7*171,7±3,7*1to 219.5±17,1*184,3±3,5*1
3Patients with angina III FC SD and severe (n=53)to 107.7±13,4*1,283,7±5,3*1,2236,5±15,5*1,2of 97.8±5,9*1,2
Therapy nitrosorbid
4Patients with angina II FC and SD moderate (n=14)89,8±7,3*166,9±3,9*1198,6±18,2*178,6±3,2*1
5Patients with angina III FC SD and severe (n=14)95,7±9,7*179,5±4,7*1RUR 219.7±13,3*191,8±5,3*1
Therapy enalapril 20 mg + trental 400 mg
6Patients with angina II FC and SD moderate (n=37)40,3±7,8*1,2,414,9±2,9*1,2,444,3±5,3*1,2,424,5±2,1*1,2,4
Therapy amlodipine 30 mg + trental 400 mg
7Patients with angina III FC SD and severe (n=39)61,2±6,1*1,3,515,3±3,4*3,581,4±10,3*1,3,523,5±3,1*3,5

Table 4
Dynamics of indicators of the complement system in patients with CHD and DM on therapy.
№ p/pThe group surveyedComplement
CH50heme. edWith3edWith4ed
1Control (n=37)66,9±2,780,41±0,020,19±0,02
Before the treatment
2Patients with angina II FC and SD moderate (n=51)54,3±2,69*10,87±0,06*10,49±0,03*1
3Patients with angina III FC SD and severe (n=53)50,3±2,53*1,20,98±0,09*1,20,58±0,07*1,2
Therapy nitrosorbid
4Patients with angina II FC and SD moderate (n=14)56,5±2,33*10,85±0,05*10,47±0,03*1
5Patients with angina III FC SD and severe (n=14)51,4±2,63*10,95±0,05*10,57±0,05*1
Therapy enalapril 20 mg + trental 400 mg
6Patients with angina II FC and SD moderate (n=37)63,5±2,91*2.4GHz0,45±0,02*2.4GHz0,23±0,03*2.4GHz
Therapy amlodipine 30 mg + trental 400 mg
7Patients with angina III FC SD and severe (n=39)60,1±2,65*1,3,50,56±0,07*1,3,50,43±0,05*1,3,5

Here are clinical observation # 1:

Patient M., aged 52, was admitted to cardiology Department in December 2002, complaining of attacks of angina pain and shortness of breath when walking over a distance of 100 m and stairs to the 2nd floor, weakness, dry mouth, thirst, pain in the lower extremities during walking. Ill with diabetes for 7 years, had received treatment with maynila (2 pills a day), decompensation of diabetes explains the violation of the diet. In the last 4 years in a patient experiencing seizures stenocarditiceski pain, for which he took nitrosorbid.

Over the past month condition worsened: increased signs of decompensation of diabetes mellitus, increased frequency and intensity of attacks chest pain, shortness of breath during exercise, and therefore sought medical help. Of illness marks the flu, appendectomy in 1984. When receiving a satisfactory condition, normostenik. Skin and visible mucous regular color, the skin is dry, reduced turgor. Peripheral edema no. Vesicular breathing in lungs. The number of 20 breaths in 1 minute. The left border of the heart is determined at the level srednechrochnoy line. Heart sounds loud, accent II tone of the aorta. Regular rhythm, heart rate 82 in 1 minute. AD - 140/90 mm Hg wet Tongue is, lined with whitish bloom. The belly of the usual form, palpation painless. The size of the liver by karlovu: 14-10-8 cm, palpation painless. In General, the analysis of blood and urine revealed no pathology. The level of HbA1C - 8%. ECG: sinus rhythm right, signs of chronic coronary insufficiency. Echocardiography: diastolic dysfunction of the left ventricle. VEM: the test is terminated when the load level of 75 watts in connection with the occurrence of pain, accompanied by a horizontal ST segment depression V5,6at 1 mm, which has continued up to 4-5 min rest. Conclusion: tolerance to physical load is below average. The signs of coronary insufficiency, corresponding strokes voltage and II, respectively.

Indicators of immune status: CD4+ 34,2%; CD8+ - 50,9%; CD25+ - 20,1%; CD95+ - 4,7±0,05%; HLA-DR+ 24,8±2,9%; IgM - 2.7 g/l; IgG - 17.3 g/l; IL-1β 284,5 PCG/ml; IL-6 to 112.4 PCG/ml; IL 184,5 PCG/ml; TNFα 468,4 PCG/ml; neopterin - 23.5 nmol/l; activity of the complement system: CH50- 55,4 heme; C3- 0,84%; With4- 0,48%

Examined by an ophthalmologist, conclusion: angiopathy of the retina. Examined by a neurologist: sensory polyneuropathy of the lower extremities, RVG lower limbs: lower blood vessels of the lower extremities. In a patient diagnosed with diabetes mellitus type 2, moderate severity, decompensation. Diabetic m is creamypie: angiopathy of the retina; sensory polyneuropathy of the lower extremities. Macroangiopathy of the lower extremities. Coronary heart disease: stable angina II functional class. N. I.

He was appointed therapy: enalapril (20 mg/day), trental (400 mg/day). On the background of treatment achieved clinical remission: reduction of FC angina and heart failure. When control of Bicycle ergometry increased tolerance to physical activity. ECG monitoring: reducing the frequency and duration of ischemic episodes.

Immune status: CD4+ 40,3%; CD8+ - 28,9%; CD20+ 16,2%; CD25+ - 14,9±1,2%; CD95+ - 4,3±0,04%; HLA-DR+ 23,8±2,7%; IgM was 1.43 g/l; IL-1β - 61,8 PCG/ml; IL-6 - 21,3 PCG/ml; TNFα - 72,3 PCG/ml; neopterin and 12.4 nmol/l; CH50- 66,3 heme. units; (C3- 0,48%; With4- 0,21%

The patient was discharged from the hospital with the recommendation of the re-inspection after 1-2 months.

Clinical observation # 2:

Patient D., aged 57, was admitted to the cardiology Department in February 2003, complaining of attacks of angina pain and shortness of breath when walking at a distance less than 100 m or climbing stairs to 1st floor, General weakness, pain in the legs when walking. Sick diabetes for 9 years, had received treatment (monotard + siofor 850). In the last 3 years in a patient with angina, about which periodically took nitrosorbid.

On the bushes last month condition worsened: increased frequency of attacks of chest pain, shortness of breath during exercise, and therefore sought medical help. Of illness notes ARI, pneumonia. When receiving a satisfactory condition, hypersthenics (BMI body > 30 kg/m2). Skin and visible mucous regular color, the skin is dry, reduced turgor. Peripheral edema no. Vesicular breathing in lungs. The number of breaths 19 per minute. The left border of the heart is determined at the level srednechrochnoy line. Muffled heart sounds, accent II tone of the aorta. Regular rhythm, heart rate is 78 per minute. AD - 160/90 mm Hg wet Tongue coated yellowish-white tint. The belly of the usual form, palpation painless. The size of the liver by karlovu: 14-9-8 see In the General analysis of blood revealed no pathology. In the General analysis of urine: reduction beats. density up to 1015, proteinuria - 0.01 g/l, hyaline cylinders in 1-2 p/SP. The level of HbA1C - 6.9 per cent. ECG: sinus rhythm right, signs of chronic coronary insufficiency. Echocardiography: diastolic dysfunction of the left ventricle. VEM: the test is terminated at a load of 50 watts with the advent stenocarditiceski pain.

Indicators of immune status: CD4+ 56,2%, CD8+ - 13,9%, CD20+ 26,5%, IgG - 17.5 mg/ml, IgM - 1.7 mg/ml, neopterin blood - 13.5 nmol/l, IL-1β - to 107.7 PG/ml, IL-6 - 83,7 PG/ml, TNFα - 236 PG/ml, IL-4 - 97 PG/ml the Activity of the complement system:3- 0,98%, With4- 0,58%, With the 50- 50,3%

Examined by an ophthalmologist, conclusion: preproliferative retinopathy. Examined by a neurologist, conclusion: sensory polyneuropathy of the lower extremities.

RVG vessels of lower extremities: lower blood vessels of the lower limb II Art.

In a patient diagnosed: coronary heart disease: stable angina of FC III. N. I. Arterial hypertension I tbsp. Sugar type 2 diabetes, severe, subcompensated. Diabetic microangiopathy: preproliferative retinopathy; nephropathy, sensory polyneuropathy of the lower extremities. Macroangiopathy lower extremities II Art.

He was appointed therapy: enalapril (30 mg/day), trental (400 mg/day). On the background of treatment achieved positive clinical dynamics. Decreased the number of strokes from 11 to 3 per week, reduced need for nitroglycerin. When control of Bicycle ergometry increased tolerance to physical activity. ECG monitoring: reducing the frequency and duration of ischemic episodes.

Immune status: CD4+ and 42.3%, CD8+ - 21,9%, CD20+ 12.7%), and IgG - 12,8 mg/ml, IgM was 1.43 mg/ml, neopterin - 9.4 nmol/L.

Cytokine status: IL-1β - 66,7 PG/ml, IL-6 and 18.5 PG/ml, TNFα - 81,3 PG/ml, IL-4 - of 25.6 PG/ml the Activity of complement:3- 0,54%, With4at 0.42%, SN50- 61,1%

The patient was discharged from Stazione is and with the recommendation of the re-inspection after 1-2 months.

These clinical examples demonstrate high clinical and immunomodulator effectiveness of the combined treatment with enalapril and answered in patients with coronary artery disease on the background of type 2 diabetes.

Thus, the method can be used in clinical practice in patients with CHD and diabetes of varying severity, because along with clinical remission allows to achieve an effective immune that allows you to control the progression of the atherosclerotic process, angiopathies and coronary heart disease, to improve the prognosis of the disease.

Method of correction of immune disorders in patients with ischemic heart disease and diabetes mellitus type 2, characterized in that use enalapril 20 mg/day in combination with answered 400 mg/day for angina II functional class and diabetes type 2 moderate; enalapril (30 mg/day in combination with answered 400 mg/day in strokes III functional class and diabetes type 2 heavy flow.



 

Same patents:

FIELD: medicine.

SUBSTANCE: method involves administering required dose of renin-angiotensin inhibitor Ramipryl or its salt combined with a hypotensive drug, means for reducing cholesterol content, diuretic or aspirin to patients showing no signs of left ventricle dysfunction or cardiac insufficiency.

EFFECT: prevented cardiovascular attacks, angina pectoris, diabetes manifestations.

18 cl, 5 tbl

FIELD: medicine.

SUBSTANCE: method involves administering Eucanol at a daily dose of 3-4 g and Ispradin at a daily dose of 1.2-1.3 mg twice a day. Eucanol is taken during a meal and Ispradin is taken 30-40 min before meals.

EFFECT: enhanced effectiveness of treatment; reduced drug consumption.

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to pharmaceutically acceptable salts of 2,4,6-trimethyl-2-hydroxypyridine with lower dicarboxylic acids of the general formulae (1-a-d): possessing an antioxidant activity wherein X means a simple bond (compound 1a), oxalate, C8H11NO x C2H2O4; X means -CH2 (compound 1b), malonate, C8H11NO x C3H4O4; X means -CH2-CH2 (compound 1c), succinate, C8H11NO x C4H6O4); X means the group -CH2CH(OH) (compound 1d), malate, C8H11NO x C4H6O5. Also, invention relates to a pharmaceutical composition of salt of the formula (1c) possessing geroprotecting and anti-ischemic activities, and to a method for preparing these salts.

EFFECT: improved preparing method, valuable medicinal properties of substances and pharmaceutical composition.

3 cl, 5 tbl, 6 ex

FIELD: medicine.

SUBSTANCE: method involves additionally administering vitamins B6, B12 and folic acid to patients receiving anticoagulation therapy. Protein content is limited in daily food allowance to 0.8-1.1 g/kg of body weight and cysteine content is increased to 400-500 mg/day.

EFFECT: enhanced effectiveness of treatment; eliminated homocysteine link in pathogenesis.

FIELD: medicine.

SUBSTANCE: method involves administering Clonidine (Clophelinum). The drug is introduced intramuscularly, intravenously or as pills on the background of neurotropic therapy at a dose of 2.5-3.0 mcg/kg of body weight during the first hours of posttraumatic period within 7-10 days.

EFFECT: accelerated and simplified treatment course.

1 dwg, 1 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of 5-amidino-2-hydroxybenzenesulfonamide of the general formula (I): wherein R2 means hydrogen atom (H), lower alkyl that can comprise a substitute chosen from the group (A): wherein (A) means -COORA, -CONRBRC, 3-7-membered monocyclic heterocycloalkyl group comprising one or two heteroatom in ring chosen from atoms N, O, S that can comprise oxo-group and 5-6-membered monocyclic aromatic heterocyclic group comprising one-three heteroatoms in ring chosen from atoms N, O, S that can comprise oxo-group or lower alkyl wherein RA means hydrogen atom (H), 3-7-membered monocyclic aliphatic alkyl group, lower alkyl that can comprises a substitute chosen from the group (i) wherein (i) means -COORA1 wherein RA1 means hydrogen atom (H), -OCORA2 wherein RA2 means lower alkyl group, -OCOORA3 wherein RA3 means lower alkyl, -ORA4 wherein RA4 means hydrogen atom (H), lower alkyl -CONRA5RA6 wherein RA5 and RA6 mean independently hydrogen atom (H), lower alkyl, or -NRA5RA6 forms 5-6-membered monocyclic amino-group comprising one heteroatom in ring chosen from atoms N, O, S and another one distinct from nitrogen atom (N) instead a bond; wherein RB and RC mean independently hydrogen atom (H), lower alkyl that can comprise a substitute chosen from the group (ii), or -NRBRC forms 5-6-membered monocyclic amino-group comprising one heteroatom in ring chosen from atoms N, O, S and another one distinct from nitrogen atom (N) instead a bond; (ii) means -COORB1 wherein RB1 means hydrogen atom (H), lower alkyl; T means oxygen atom (O), sulfonyl group; or TR1 means -SO2NRB3RC3 wherein RB3 and RC3 means independently hydrogen atom (H), lower alkyl; R2 means lower alkyl, phenyl that can comprise one-three substitutes chosen from the group (B) wherein (B) means halogen atom, -COORE, sulfamoyl, lower alkylsulfonyl wherein RE means lower alkyl; Q means hydrogen atom (H), lower alkyl that can comprise a substitute chosen from the group (D) wherein (D) means 5-6-membered monocyclic aromatic heterocyclic group that can comprise one-three heteroatom chosen from atoms N, O, S that can comprise a substitute chosen from the group (iv) wherein (iv) means oxo-group, lower alkyl; Z means hydrogen atom (H), hydroxyl group (OH), -COORN wherein RN means lower alkyl that can comprise a substitute chosen from the group (viii) wherein (viii) means -OCOR5 wherein RN5 means lower alkyl that can comprise -OCORN51 wherein RN51 means lower alkyl; or its pharmaceutically acceptable salt. Compounds of the formula (I) inhibit activated factor X in blood coagulation system that allows their using in pharmaceutical composition. Also, invention describes intermediate compounds.

EFFECT: valuable medicinal properties of compounds and compositions.

12 cl, 5 tbl

FIELD: medicine, cardiology.

SUBSTANCE: invention proposes an agent for correction of abdominal complications in acute period in myocardium infarction. Proposed agent represents ondansetron or domperidone. Agent reduces frequency of hyperemia occurring, improved indices of intestine contractions, promotes to declining lethality in acute period in myocardium infarction.

EFFECT: improved and valuable medicinal properties of agent.

4 tbl, 6 dwg

FIELD: medicine, pharmacy.

SUBSTANCE: invention proposes a pharmaceutical preparation based on angiotensin-converting enzyme inhibitor, its using in prophylaxis of insult, diabetes and/or congestive cardiac insufficiency and corresponding methods for its using in patient with maintenance heart function and subjected for risk of cardiovascular attack due to previous history of ischemic disease, insult or peripheral arterial disease. In particular, inhibitor of angiotensin-converting enzyme can be chosen from ramipril, ramiprilat, lisinopril, enalapril and enalaprilat. Invention promotes to reducing the total lethality of patients group in case of cardiovascular diseases, cardiac attacks and insults, the necessity for carrying out procedures for revascularization (such as surgery operation for coronary shunt, angioplasty with using balloon and so on) and diabetic complication are diminished.

EFFECT: improved and valuable medicinal properties of preparations.

19 cl, 1 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to using a pharmaceutical preparation comprising beta-blocking agent in the maintenance dose less 50 mg, in particular, in the range from 25 mg to 47 mg in mixture with a pharmaceutically acceptable adjuvant, vehicle or carrier. The preparation is used in treatment of atherosclerosis and diseases associated with thereof. Invention provides decreasing dose of the preparation.

EFFECT: improved using method.

6 cl, 3 tbl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivative of triazaspiro[5.5]undecane of the formula (I): wherein R1 means compound of the formula (1): or (2): wherein G represents a bond, (C1-C4)-alkylene, (C2-C4)-alkenylene or -CO-; ring A represents: (1) C5-10-membered mono- or bicarbocyclic ring or (2) 5-10-membered mono- or bicyclic heterocycle comprising 1-2 nitrogen atoms and/or 1-2 oxygen atoms; substitute R6 means the following values: (1) (C1-C4)-alkyl, (2) halogen atom, (3) nitrile group, (4) trifluoromethyl group and others; R2 represents: (1) (C1-C4)-alkyl, (2) (C2-C4)alkynyl or (3) (C1-C4)-alkyl substituted with a substitute represented in claim 1 of the invention claim; each R3 and R4 represents independently: (1) hydrogen atom, (2) (C1-C4)-alkyl or (3) (C1-C4)-alkyl substituted with 1-2 substituted taken among: (a) Cyc 2 and (b) hydroxy-group (wherein Cyc 2 represents (1) C5-6-membered monocarbocyclic ring or (2) 5-6-membered monocyclic heterocycle comprising 1-2 nitrogen atoms and/or one oxygen atom), or R3 and R4 form in common group of the formula: wherein R26 represents (C1-C4)-alkyl or Cyc 2; R5 represents hydrogen atom or (C1-C4)-alkyl, its quaternary ammonium salt, its N-oxide or its nontoxic salt. Also, invention relates to pharmaceutical composition inhibiting HIV, regulator of chemokine/chemokine receptor and agent used in treatment and prophylaxis of some diseases, such as inflammatory diseases, asthma, atopic dermatitis, nettle rash, allergic diseases, nephritis, hepatitis, arthritis and other diseases that comprise as an active component above described compound of the formula (I) or its quaternary ammonium salt, its N-oxide or its nontoxic salt. Also, invention relates to (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane or its pharmaceutically acceptable salt and pharmaceutical composition based on thereof, and to (3R)-1-butyl-2,5-dioxo-3-((1R)-1-hydroxy-1-cyclohexylmethyl)-9-(4-(4-carboxyphenyloxy)phenylmethyl)-1,4,9-triazaspiro[5.5]undecane hydrochloride and pharmaceutical composition based on thereof.

EFFECT: valuable medicinal properties of derivative and composition.

16 cl, 32 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to substituted bicyclic heterocyclic compounds of the formula (I): their tautomeric forms, stereoisomers, polymorphous forms, pharmaceutically acceptable salts and pharmaceutically acceptable solvates wherein groups R1, R2, R3 and R4, and groups R5 and R6 when they are bound with carbon atom they represent hydrogen, halogen atom, hydroxy-group, alkyl, alkoxy-group; R5 and R6 as a single group or both can represent also an oxo-group when they are bound with carbon atom; when R5 and R6 are bound with nitrogen atom then they represent hydrogen atom, hydroxy-group or such unsubstituted groups as alkyl, alkoxy-group, aralkyl. X means oxygen or sulfur atom; Ar means phenylene, naphthylene or benzofuryl. Proposed compounds can be used against obesity and hypercholesterolemia. Also, the invention describes methods for preparing compounds, pharmaceutical compositions, method for treatment and using compounds proposed.

EFFECT: valuable medicinal properties of compounds and compositions.

52 cl, 77 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new compounds including all its enantiomeric and diastereomeric forms, and to their pharmaceutically acceptable salts wherein indicated compound corresponds to the formula: wherein A represents a conformationally limited ring system chosen from the group comprising the following formulae: (a) (d) and (e) wherein carbon atoms labeled by asterisks can be in any stereochemical configuration or their mixtures wherein Y has a formula: -(CH2)b-R15 wherein index b = 1-4, and R15 represents -OH, -NH2, guanidine-group, and Z has a formula: wherein R represents hydrogen atom; R9 represents naphthylmethyl; R10 represents -C(X)N(R16)2 wherein each R16 represents independently hydrogen atom or (C1-C10)-alkyl; X represents oxygen atom; or Z represents naphthylmethyl wherein W has a formula: wherein R represents phenyl substituted optionally with halogen atom of OH-group wherein fragment L is chosen from the group comprising: -NH- or -NHC(O)-; B represents hydrogen atom of fragment of the formula: wherein fragments R2, R3 and R4 are chosen independently among the group comprising hydrogen atom, -NHC(O)CH3, benzyl substituted optionally with hydroxy-group or halogen atom, imidazolylmethyl; or fragments R2, R3 and R represent in common naphthalinyl or isoquinolinyl; or one radical among R2, R3 and R4 represents hydrogen atom and two radical among R, R3 or R4 chosen in common form piperidine ring or tetrahydroisoquinoline ring substituted optionally with the group -C(O)CH3. Also, invention relates to a pharmaceutical composition possessing the agonistic activity with respect to MC-3/MC-4 receptors based on these compounds. Invention provides preparing new compounds and pharmaceutical compositions based on thereof for aims in treatment of disorders mediated by function of MC-3/MC-4 receptors.

EFFECT: valuable medicinal properties of compounds and compositions.

17 cl, 14 tbl, 12 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new compounds of the general formula (I) in racemic form, enantiomer form or in any combinations of these forms possessing affinity to somatostatin receptors. In the general formula (I): R1 means phenyl; R2 means hydrogen atom (H) or -(CH2)p-Z3 or one of the following radicals: and Z3 means (C3-C8)-cycloalkyl, possibly substituted carbocyclic or heterocyclic aryl wherein carbocyclic aryl is chosen from phenyl, naphthyl and fluorenyl being it can be substituted, and heterocyclic aryl is chosen from indolyl, thienyl, thiazolyl, carbazolyl, or radicals of the formulae and and it can be substituted with one or some substitutes, or also radical of the formula: R4 means -(CH2)p-Z4 or wherein Z4 means amino-group, (C1-C12)-alkyl, (C3-C8)-cycloalkyl substituted with -CH2-NH-C(O)O-(C1-C6)-alkyl, radical (C1-C6)-alkylamino-, N,N-di-(C1-C12)-alkylamino-, amino-(C3-C6)-cycloalkyl, amino-(C1-C6)-alkyl-(C3-C6)-cycloalkyl-(C1-C6)-alkyl, (C1-C12)-alkoxy-, (C1-C12)-alkenyl, -NH-C(O)O-(C1-C6)-alkyl, possibly substituted carbocyclic or heterocyclic aryl; p = 0 or a whole number from 1 to 6 if it presents; q = a whole number from 1 to 5 if it presents; X means oxygen (O) or sulfur (S) atom n = 0 or 1. Also, invention relates to methods for preparing compounds of the general formula (I), intermediate compounds and a pharmaceutical composition. Proposed compounds can be used in treatment of pathological states or diseases, for example, acromegaly, hypophysis adenomas, Cushing's syndrome and others.

EFFECT: improved preparing method, valuable medicinal properties of compounds and composition.

11 cl, 2 tbl

FIELD: medicine.

SUBSTANCE: method involves administering required dose of renin-angiotensin inhibitor Ramipryl or its salt combined with a hypotensive drug, means for reducing cholesterol content, diuretic or aspirin to patients showing no signs of left ventricle dysfunction or cardiac insufficiency.

EFFECT: prevented cardiovascular attacks, angina pectoris, diabetes manifestations.

18 cl, 5 tbl

FIELD: medicine, endocrinology.

SUBSTANCE: invention elates to a method for treatment of diabetes mellitus type 2, method for declining the glucose content in patient blood and method for reducing resistance to insulin, diminishing the hemoglobin A1c content, enhancing the insulin level after eating, and reducing the amplitude change content ("mobility") of glucose in diabetic patients. Method involves administration of metformin to patient in the low dose (160-750 mg) in combination with the second anti-diabetic agent chosen from the group including glucose oxidase inhibitor, glucagons-like peptide-1 (GLP-1), insulin, α/β-double agonist of PRAP other than thiazolidinedione, meglitimide and inhibitor aP2 wherein the second anti-diabetic agent is administrated as a daily dose in interval between the initial daily dose comprising 20-60% of the initial daily dose of this anti-diabetic agent used in usual medicinal practice in therapy of the first order in treatment of diabetes mellitus up to the daily supporting dose comprising 40-60% of the daily supporting dose of this anti-diabetic agent used in usual medicinal practice as therapy of the first order in treatment of diabetes mellitus. Invention provides the effectiveness in treatment of diabetes mellitus that is equivalent practically to effectiveness of treatment by using combination of metformin and other indicated anti-diabetic agent used in doses prescribing in usual medicinal practice but with significantly less adverse effects.

EFFECT: improved method for treatment of diabetes mellitus.

7 cl, 10 dwg, 4 tbl, 3 ex

FIELD: medicine, endocrinology, in particular treatment of diabetus mellitus type 2 in patient didn't use anti-diabetic drugs.

SUBSTANCE: claimed method includes simultaneous administration of metformine in daily dose of 160-750 mg and gliburide in daily dose of 0.5-15 mg. Gliburide has grain-size classification wherein min.10 % particles have size less than 2 mum and max.10 % particles have size more than 60 mum.

EFFECT: treatment of improved effectiveness with decreased drug doses and reduced side effects.

24 cl, 10 dwg, 4 ex, 4 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of diphenylazathedinone of the general formula (I): wherein R1, R2, R3 and R4 mean independently of one another (0-C30)-alkylene-L wherein one or some C-atoms of alkylene residue can be substituted with -O-, -(C=O)- or -NH- and, except for, R1-R6 can represent hydrogen atom (H), fluorine atom (F), and L represents compound of the formula: , and their pharmaceutically tolerated salts also. Compounds of the formula (I) elicit hypolipidemic effect and can be used in therapeutic aims. Also, invention describes a medicinal agent and its using.

EFFECT: valuable medicinal properties of compounds.

7 cl, 31 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition used for stabilization of homeostasis and arresting pathological processes in the body. Invention proposes a pharmaceutical composition as powder with particles size from 250 to 400 mcm comprising the following components by the first variant, wt.-%: carbon, 10.01-53.02; oxygen, 30.10-53.10; potassium, 0.26-1.99, and calcium, 0.20-31.37, and comprising the following components by the second variant, wt.-%: calcium, 0.35-31.20; carbon, 10.99-50.21; oxygen, 34.55-51.03; sulfur, 0.73-14.81, and phosphorus, 0.08-3.30. Invention provides compensation of trace elements unbalance that causes and accompanies many diseases, possibility for stabilization of trace element homeostasis and arresting pathological processes of different etiology.

EFFECT: improved and valuable medicinal properties of composition.

12 cl, 13 ex

FIELD: chemistry of organophosphorus compounds, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new bisamidate phosphonate compounds that are inhibitors of fructose 1,6-bis-phosphatase. Invention describes a compound of the formula (IA): wherein compound of the formula (IA) is converted in vivo or in vitro to compound of the formula M-PO3H2 that is inhibitor of fructose 1,6-bis-phosphatase and wherein M represents R5-X- wherein R5 is chosen from a group consisting of compounds of the formula or wherein each G is chosen from the group consisting of atoms C, N, O, S and Se and wherein only one G can mean atom O, S or Se and at most one G represents atom N; each G' is chosen independently from the group consisting of atoms C and N and wherein two G' groups, not above, represent atom N; A is chosen from the group consisting of -H, -NR42, -CONR42, -CO2R3, halide, -S(O)R3, -SO2R3, alkyl, alkenyl, alkynyl, perhaloidalkyl, haloidalkyl, aryl, -CH2OH, -CH2NR42, -CH2CN, -CN, -C(S)NH2, -OR2, -SR2, -N3, -NHC(S)NR42, -NHAc, or absent; each B and D is chosen independently from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclyl, aralkyl, alkoxyalkyl, -C(O)R11, -C(O)SR11, -SO2R11, -S(O)R3, -CN, -NR92, -OR3, -SR3, perhaloidalkyl, halide, -NO2, or absent and all groups except for -H, -CN, perhaloidalkyl, -NO2 and halide are substituted optionally; E is chosen from the group consisting of -H, alkyl, alkenyl, alkynyl, aryl, alicyclyl, alkoxyalkyl, -C(O)OR3, -CONR42, -CN, -NR92, -NO2, -OR3, -SR3, perhaloidalkyl, halide, or absent; all groups except for -H, -CN, perhaloidalkyl and halide are substituted optionally; J is chosen from the group consisting of -H, or absent; X represents optionally substituted binding group that binds R5 with phosphorus atom through 2-4 atoms comprising 0-1 heteroatom chosen from atoms N, O and S with exception that if X represents urea or carbamate then there are 2 heteroatoms that determine the shortest distance between R5 and phosphorus atom and wherein atom bound with phosphorus means carbon atom and wherein X is chosen from the group consisting of -alkyl(hydroxy)-, -alkynyl-, - heteroaryl-, -carbonylalkyl-, -1,1-dihaloidalkyl-, -alkoxyalkyl-, -alkyloxy-, -alkylthioalkyl-, -alkylthio-, -alkylaminocarbonyl-, -alkylcarbonylamino-, -alkoxycarbonyl-, -carbonyloxyalkyl-, -alkoxycarbonylamino- and -alkylaminocarbonylamino- and all groups are substituted optionally; under condition that X is not substituted with -COOR2, -SO3H or -PO3R22; n means a whole number from 1 to 3; R2 is taken among the group -R3 and -H; R3 is chosen from the group consisting of alkyl, aryl, alicyclyc and aralkyl; each R4 is chosen independently from the group consisting of -H and alkyl, or R4 and R4 form cycloalkyl group; each R9 is chosen independently from the group consisting of -H, alkyl, aryl, aralkyl and alicyclyl, or R9 and R9 form in common cycloalkyl group; R11 is chosen from the group consisting of alkyl, aryl, -NR22 and -OR2; each R12 and R13 is chosen independently from the group consisting of hydrogen atom (H), lower alkyl, lower aryl, lower aralkyl wherein all groups are substituted optionally, or R12 and R13 in common are bound through 2-5 atoms comprising optionally 1-2 heteroatoms chosen from the group consisting of atoms O, N and S to form cyclic group; each R14 is chosen independently from the group consisting of -OR17, -N(R17)2, -NHR17, -NR2OR19 and -SR17; R15 is chosen from the group consisting of -H, lower alkyl, lower aryl, lower aralkyl, or in common with R16 is bound through 2-6 atoms comprising optionally 1 heteroatom chosen from the group consisting of atoms O, N and S; R16 is chosen from the group consisting of -(CR12R13)n-C(O)-R14, -H, lower alkyl, lower aryl, lower aralkyl, or in common with R15 is bound through 2-6 atoms comprising optionally 1 heteroatom chosen from the group consisting of atoms O, N and S; each R17 is chosen independently from the group consisting of lower alkyl, lower aryl and lower aralkyl and all groups are substituted optionally, or R17 and R17 at atom N are bound in common through 2-6 atoms comprising optionally 1 heteroatom chosen from the group consisting of atoms O, N and S; R18 is chosen independently among the group consisting of hydrogen atom (H), lower alkyl, aryl, aralkyl, or in common with R12 is bound through 1-4 carbon atoms forming cyclic group; each R19 is chosen independently from the group consisting of -H, lower alkyl, lower aryl, lower alicyclyl, lower aralkyl and -COR3; and under condition that when G' represents nitrogen atom (N) then the corresponding A, B, D or E are absent; at least one from A and B, or A, B, D and E is chosen from the group consisting of -H, or absent; when G represents nitrogen atom (N) then the corresponding A or B is not halide or group bound directly with G through a heteroatom; and its pharmaceutically acceptable salts. Also, invention describes a method for treatment or prophylaxis of diabetes mellitus, a method for inhibition of activity 0f fructose 1,6-bis-phosphatase, a method for decreasing blood glucose in animals, a method for treatment of diseases associated with glycogen deposition, a method for inhibition of gluconeogenesis in animal and a pharmaceutical composition based on compounds of the formula (IA).

EFFECT: valuable medicinal and biochemical properties of compounds.

69 cl, 7 tbl, 64 ex

FIELD: medicine, pharmacy.

SUBSTANCE: invention relates to a pharmaceutical composition made mainly as solid medicinal formulations and comprising therapeutically effective amount of gliclazide and the special additive in the amount 4.65-6.70 mass. p. per mass unit of active substance. The additive comprises hydroxypropylmethylcellulose, microcrystalline cellulose, aerosil and stearate taken in the following ratio of components, mass. p. per 1 m. p. of active substance: hydroxypropylmethylcellulose, 2.50-3.50; microcrystalline cellulose, 2.12-3.00; aerosil, 0.01-0.05, and stearate, 0.02-0.15. Proposed pharmaceutical composition provides the sustained-release of gliclazide and high bioavailability of active substance, a simple method for its preparing as compared with solid medicinal formulation of gliclazide known from the prior art.

EFFECT: improved and valuable properties of composition.

3 cl, 2 tbl, 3 ex

FIELD: organic chemistry, neurology, medicine.

SUBSTANCE: invention relates to a new medicinal agent used in treatment of feeble-mindedness comprising a derivative of 2-aryl-8-oxodihydropurine, namely, a derivative of 2-aryl-8-oxodihydropurine that comprises acetamide group at position 7 or 9 of purine ring. Invention proposes compounds of formulae (Ia) and (Ib) wherein radicals X1, Y1, R12, R13, R22, R23, R32, R42 and R43 have the corresponding values, or their pharmaceutically acceptable acid-additive salt. Also, invention proposes using compounds of the formulae (Ia) and (Ib) or their pharmaceutically acceptable acid-additive salt for preparing a medicinal agent used in treatment or prophylaxis of feeble-mindedness wherein feeble-mindedness represents deterioration of the teaching process, dysmnesia, dysmnesia-based disorientation, mental dysfunction, Alzheimer's disease, cerebrovascular feeble-mindedness and/or senile feeble-mindedness, and in treatment or prophylaxis of higher cerebral dysfunction. Invention provides the development of a medicinal preparation for prophylaxis or treatment of feeble-mindedness symptoms associated with diseases that can induce feeble-mindedness and higher cerebral dysfunction.

EFFECT: valuable medicinal properties of agents.

12 cl, 3 tbl, 5 ex

Up!