Diagnostic technique for antihypertensive drug tolerance

FIELD: medicine.

SUBSTANCE: therapeutic course involves examination that implies photography of eye-ground vessels and measurement of diametre of retinal vessels on an empty stomach of the patient prior to and after administration of a medicine. Observed increase in diametre of supero-temporal branch of central retinal artery at a distance of one vertical diametre of disk of optic nerve from an edge of disk of optic nerve by 10% and more from the initial one ensures to diagnose efficiency of the administered medicine. The absence of increase in diametre of supero-temporal branch of central retinal artery by 10% and more in administration of the same dosage of the medicine enables to diagnose development of tolerance.

EFFECT: method extends range of means to determine antihypertensive drug tolerance.

3 ex

 

The invention relates to medicine, namely to methods of diagnosing pathological conditions, and can be used for the diagnosis of tolerance to the antihypertensive drugs.

Therapy of hypertension is based on a regular, long-term, usually lifelong use of antihypertensive drugs [Makolkin VI the Phenomenon of "escapes" in the treatment of hypertension. // Russian medical journal. - 2001. - No. 1 - p.14-16; Nesterov SCI, Teplyakov A.T., Soeva VI the Efficacy and tolerability of ACE inhibitor of invoria and blocker ATI-receptors of angiotensin II diovan in patients with arterial hypertension stage I-II. // Clinical medicine. - 2002. - No. 8 - p.46-49].

It is often initially high antihypertensive activity of the drug over time decreases up to its complete loss. In this case we speak of the reduction of antihypertensive drug individual sensitivity or the development of tolerance to it [Makolkin VI the Phenomenon of "escapes" in the treatment of hypertension // Russian medical journal. - 2001. - No. 1 - p.14-16; debut HE Place of nitrates in the modern treatment of patients with ischemic heart disease. // Cardiology. - 2005. No. 7, - pp.69-72; debut HE Debuts of coronary heart disease: a strategy for diagnosis and treatment. // Cardiovasculary therapy and prevention. - 2002. - No. 1 - p.76-83].

Under the tolerance to drugs understand the reduction of the effect of drugs in their continuous reception [Blizzard VI, debut HE, Kozyrev BTW, Oganov RG Tolerance to nitrates: new data on the mechanism of development and possibilities of correction. // Cardiology. - 1998. - No. 12 - p.56-61; debut HE Place of nitrates in modern therapy of patients with coronary heart disease. // Cardiology. - 2005. No. 7, - pp.69-72; Sumarokov A.B., Blokhin A.B., M. Menshikov, Kuzmin A.V., Chikvashvili DI, Ore MA Clinical-instrumental and biochemical study of nitrate tolerance in patients with coronary atherosclerosis. // Cardiology. - 1995. - T.35. - N 2 - p.4-8].

In relation to antihypertensive drugs also used the term "phenomenon escapes antihypertensive action" [Makolkin VI the Phenomenon of "escapes" in the treatment of hypertension. // Russian medical journal. - 2001. No. 1. - P.14-16; Nesterov SCI, Teplyakov A.T., Soeva VI the Efficacy and tolerability of ACE inhibitor of invoria and blocker ATI-receptors of angiotensin II diovan in patients with arterial hypertension stage I-II. // Clinical medicine. - 2002. No. 8. - P.46-49; Nebieridze D.V. Rilmenidine is one of the first representatives of agonists imidazoline receptors: new opportunities for treatment of arterial hypertension. // Hypertension - 2001. - Vol.8 - No. 4. - S-150; Skvortsov A.A., Nasonova, S.N., Sychev A.V. and others Combined use of angiotensin-converting enzyme inhibitor quinapril and receptor blocker 1-th type to angiotensin II of valsartan in patients with moderate chronic heart failure: is it possible to increase the degree of neurohormonal blockade and improvement of the parameters of the daily heart rate variability heart compared with monotherapy. // Therapeutic archive. - 2005. No. 8. - P.34-43; Skvortsov A.A., Mareev V.Y., S. Nasonov. and other changes in the activity of neurohormonal systems at rest and at the height of the load in patients with stable chronic heart failure during treatment with angiotensin converting enzyme inhibitors. // Russian national Congress of cardiologists, 8-11 October 2002, St. Petersburg: Abstracts of presentations. SPb; 2002, p.45; Xiu J.C., Wu p., Xu J.p. et al. Effects of long-term enalaprile and lozartan therapy of heart failure on cardiovascular aldosterone. // J. Endocrinol. Invest. 2002; 25: 463-468].

The development of tolerance to the antihypertensive drugs significantly limits the effectiveness of drug therapy and is a serious threat to patients with arterial hypertension.

The development of tolerance to medications in General is well known and very common phenomenon [Ilyukhin O.V., Statsenko M.E. Ter-Minassian, Yakovlev A. T., M. Lopatin Level of specific antibodies to captopril and therapeutic activity of the drug in the treatment of patients with arterial hypertension. // Cardiology. - 2001. No. 9. - P.60-61].

As for antihypertensive drugs, mention of tolerance to this group of drugs in the scientific literature appeared relatively recently. It should be noted that the authors are unanimous in saying that the problem of tolerance to the antihypertensive drugs can relate to each practitioner [Makolkin VI the Phenomenon of "escapes" in the treatment of hypertension. // Russian medical journal. - 2001. No. 1. - P.14-16; Skvortsov A.A., Nasonova, S.N., Sychev A.V. and others Combined use of angiotensin-converting enzyme inhibitor quinapril and receptor blocker 1-th type to angiotensin II of valsartan in patients with moderate chronic heart failure: is it possible to increase the degree of neurohormonal blockade and improvement of the parameters of the daily heart rate variability heart compared with monotherapy. // Therapeutic archive. - 2005. No. 8. - P.34-43].

Very important is the fact that today there is virtually no way adequate diagnosis of development of tolerance to the antihypertensive drugs. Of tolerance to the antihypertensive drugs today it is customary to judge by the adverse change in blood pressure profile on the background glutelin the first administration of the medicine. The level of blood pressure measured once or method Korotkova, or by conducting daily monitoring of HELL. If on a background of drug action is recorded the excess of the AD relative to normal, talk about the development of patient tolerance to the antihypertensive agent. While completely ignored recognized, described by lang, that the actual arterial hypertension has an undulating course, and periods of improvement followed by periods of worsening.

In case of tolerance to the antihypertensive drug according to the standard technique, as a rule, the drug should be discontinued and appoint a new drug (mainly empirically). Pharmacodynamics the vast majority of modern antihypertensive drugs is such that the maximum effect from their destination develops not earlier than 2-4 weeks from the start of the reception. Through the same time and made a conclusion about the appropriateness of the use of this drug as a baseline antihypertensive agents.

Thus, at least for data 2-4 weeks the patient is poorly protected from the negative influence of arterial hypertension.

The lack of reliable diagnostic criteria of tolerance to the antihypertensive drug which creates an entirely contradictory reports in the literature regarding the presence and frequency of this phenomenon - the claims that he is almost in every second patient within one year of taking the drug, up to a total denial of tolerance from the same group of antihypertensive agents [Materson B.J., Reda D.J., Cushman W.S. et al. // New Engl. J Med. - 1993. - Vol.328. - P.914-921].

Studies on patent and scientific and medical literature, we found no ways to diagnose tolerance to the antihypertensive drugs. The closest in content and technical solutions ways to evaluate the antianginal effectiveness of nitrates. However, all these methods are applicable solely to determine individual sensitivity to one group of antianginal drugs and may not be used for the diagnosis of tolerance to the antihypertensive drugs. As an example, here are the most common methods of diagnosis tolerance micropreparation.

Diagnosis of nitrate tolerance can be produced according to the frequency of angina attacks and the amount of nitroglycerin tablets. However, it is known that patients with marked improvement, as a rule, seek to increase physical activity, and those whose condition is deteriorating, on the contrary, to reduce the physical load. As a result the frequency of angina attacks and the amount of energy consumption is by nitroglycerin tablets may not accurately reflect the degree of effectiveness of micropreparative [Blizzard VI, Davydov A.B. Drugs nitrates in cardiology. / M: Medicine, 1989. - Pp.92].

There is a method of determining the development of nitrate tolerance by reducing the effect of drugs nitroglycerin in heart rate and blood pressure [Abrams J. Tolerance to organic nitrates. // Circulation. - 1986. - Vol.74. - N-6. - P.1181-1185]. However, the development of tolerance to the effect of nitrate on blood vessels may not be accompanied by a weakening of the antianginal effect [Blizzard V., Davydov A.B. Drugs nitrates in cardiology. // Medicine, 1989. - P.84]. This is because the weakening of the arterial vascular effect is not always accompanied by a reduction venodilating effect [Jahnchen E. Relationship between pharmacokinetics and pharmacodynamics of organic nitrates. // Z. Kardiol. - 1986. - Vol.75. - Suppl. 3. - P.13-15]. It venodilation effect play the main role in the mechanism of antianginal action of nitrates [Blizzard V., Davydov A.B. Drugs nitrates in cardiology. / M: Medicine, 1989. - P.84; Abomasnow. Tolerance to nitrates in the treatment of angina. // Therapeutic archive, 1989, No. 8, - t, - p.146-150].

Author's certificate No. 1394130 protected method of determining individual sensitivity to nitrates in patients with ischemic heart disease (autospid. No. 1394130, MKI G01N 33/48; bull. No. 17; 1988). This method is based on a series of ad tests with subsequent measurement of the temperature of the exhaled air 2-14 minute after each reception of nitroglycerine. At the maximum temperature determine the optimal dose of the drug. The method allows to assess individual sensitivity to nitrates in patients with ischemic heart disease, however, has several disadvantages. First of all, this method is indirect because it is based on indicators that are only indirectly can indicate the presence of hemodynamic action of nitrates, causing their antianginal effect. This undoubtedly reduces the information content of the described method. In addition, it requires multiple (3-6 times) techniques micropreparative with an interval of 10 minutes in an ever-increasing dose. There is a high risk of overdose nitrates, increase in the frequency of side effects and the patient refuses further implementation of the study. The accuracy of this process depends on the ambient temperature.

There is a method of determining the effectiveness of long-acting nitrates on the results of the paired exercise of samples described by Blizzard V.I. and co-authors in "the Problem of nitrate tolerance and the ways of its solution in patients with angina" (Therapeutic archive. - 1993. - T. - N 9. - P.34-39.). This method consists in carrying out exercise of samples before treatment (without drug) and with the first dose of the drug. Evaluation of e is the efficiency of nitrates is produced by changing the length of the repeated load within 1 hour after ingestion of nitrate compared to the baseline (Delta t) to achieve an identical criteria: reduction of ischemic ST segment type 1 mm or more through 0,08 after point j and/or angina. The drug is considered effective if ΔT≥2 min [Blizzard VI, debut HE, kokurina E.V., Kozyrev BTW, Bochkareva E.V. the Problem of nitrate tolerance and the ways of its solution in patients with angina. // Therapeutic archive. - 1993. - T. - N 9. - P.34-39]. To assess the development of tolerance to nitrates spend a third cycle ergometry at the end of the treatment micropreparative. Shortening ΔT against the backdrop of prolonged nitrate, less than 2 minutes is considered as a criterion for the development of tolerance to micropreparation [Blizzard VI, debut HE, kokurina E.V., Kozyrev BTW, Bochkareva E.V. the Problem of nitrate tolerance and the ways of its solution in patients with angina. // Therapeutic archive. - 1993. - T. - N 9. - P.34-39].

This method allows to evaluate the effectiveness of long-acting nitrates and to determine the development of tolerance to them. However, it is not possible to assess the effectiveness of short-acting nitrates because the estimated duration less than the time required for holding the Bicycle ergometry. In addition, the conduct of Bicycle ergometry is not possible in the pathology of locomotor apparatus, obliterating atherosclerosis of lower extremities, changes the terminal portion of QRs complex on electrocardiogram the e alone, poor physical fitness of the patient. Due to these reasons, conducting load tests in elderly and senile age is often not possible [Karpov Y.A. Features of the course and treatment of coronary heart disease in elderly patients. // International medical journal. - 1999. - №3-4. - S-143]. The tests with physical activity unsafe and can cause pulmonary edema, ventricular fibrillation of the heart and severe coronary insufficiency in the form of sudden coronary death or myocardial infarction [Kaltenbachm M. / Forms of exercise testing. // Detection of ischemic myocardium with exercise. / Ed. F.Looden, L.Seipel. - Berlin: Springer Verlag; New York: Heidelberg, 1982. - P.3-9; Diseases of the heart and blood vessels. A guide for physicians: 4 I. Vol. 1. / Diamond I.I., Aronov D.M., Atkov O.Y; Ed. Chazov E.I. - M.: Medicine, 1992. - S]. To test the exercise there are absolute and relative contraindications. Absolute: acute myocardial infarction (less than 4 weeks from the onset of the disease); unstable angina; circulatory failure IIB-III stage classification Strazhesko-Vasilenko; severe respiratory failure; cerebrovascular circulation; myocarditis (first 3 months); acute thrombophlebitis; acute infectious diseases; dangerous arrhythmias and conduction (early and frequent ventricular extras the tables, atrio-ventricular block II-III degree); dissecting aneurysm of the aorta.

Relative: arterial hypertension at values of blood pressure over 200/100 mm Hg; atrial fibrillation; blockade of the branches of the bundle of his; heart failure, in which you want to apply glycosides; the defeat of the main trunk of the left coronary artery; aortic stenosis; metabolic disease (diabetes mellitus, myxedema and thyrotoxicosis).

In addition, in 10% of cases of possible false-positive, and in 4-14% of cases of false negative test results [Furkalo NICHOLAS, Yanovsky, GV, Sledzevska I.K. Clinical and instrumental diagnosis of lesions of the heart and coronary vessels. - K.: Health, 1990. - P.28]. All this greatly limits the range of persons who can use the above method and reduces its reproducibility and reliability.

As a prototype, is taken Way to assess individual sensitivity to nitrates proposed Kivva NR. and Chugunova I.I. (RF patent for the invention №2132066).

The method is carried out by research vessels of the ocular fundus on remediations retinal camera (e.g., TRC-NW53/TRC-NW5SF Topcon [Japan]). The patient on an empty stomach, before taking drugs, shoots vessels of the ocular fundus remediations retinal camera. Then someone introduced NITR the t and produce a re-imaging of the fundus vessels at the time of maximum effect of the drug - 7-10 min for preparations of short action and after 1 hour for prolonged forms. Using the processing system graphical images included in the software bundle IMAGEnet for Windows, perform the mapping and processing of images before and after administration of the drug. This produces simultaneous automatic measurement of the diameter of the branches of the Central retinal vein (venules). To increase the diameter of the venules are judged on the effectiveness of the drug. The expansion of the branches of the Central retinal vein by more than 10% from the original is the criterion of the effectiveness of nitrate. No extensions venules or increase their diameter is less than 10% after administration of nitrate indicates the inefficiency of the dose of the drug. The presence of nitrate tolerance establish a consistent hold 3 research: prior to the treatment of micropreparative, after taking the first dose of nitrate and another, identical doses of the drug in the course of the treatment. To reduce the degree of expansion of the venous vessels of the ocular fundus in response to receiving micropreparative judged on the development of nitrate tolerance. The method is safe, reproducible and highly reliable. However, it is based on the assessment of the response of the venous bed infusion, whereas the point of application of the vast majority antihype tentunya drugs are blood vessels. The number of antihypertensive drugs did not have on venous vessels no action. In addition, the prototype is not clearly defined vessel itself (what branch of the Central vein), and the point at which to measure the diameter of the vessel.

However, we emphasize again that all of the above methods, including the prototype, designed for the detection of nitrate tolerance or evaluation of an individual's sensitivity to them and may not be applied for the diagnosis of tolerance to the antihypertensive drugs.

The aim of the present invention is the identification of tolerance to different groups of antihypertensive drugs.

The proposed method is carried out by repeated studies of arterial vessels of the ocular fundus on remediations retinal camera. The patient on an empty stomach, before taking drugs, shoots vessels of the ocular fundus remediations retinal camera (for example, TRC-NW53/TRC-NW5SF Topcon [Japan]). Then the patient is administered antihypertensive drug and produce a re-imaging of the fundus vessels at the time of maximum effect of the drug through 20-30 minutes with sublingual admission and 1.5 hours after oral administration. Using the processing system graphical images included in the software bundle IMAGEnet for Windows, perform CT the licensing and processing of images before and after administration of the drug. This produces simultaneous automatic measurement of the diameter of the top-temporal branch of the Central artery of the retina at a distance of one vertical diameter of the optic disc from the edge of the optic disc. To increase the diameter of the artery in 10% or more of the original judge on the original drug's efficacy. For the diagnosis of tolerance produce a re-test with antihypertensive drug with the aforementioned method.

The presence of tolerance to the antihypertensive drug is establish a consistent hold 3 research: before treatment, after taking the first dose of antihypertensive drug and another, identical doses of the drug in the course of the treatment. In the absence of the expansion of the top-temporal branch of the Central artery of the retina in response to receiving antihypertensive drug by 10% or more from the original judge on the development of tolerance to it.

Example 1.

Patient P., 76 years old, diagnosis: hypertension Art. II, H1.

To determine the source of sensitivity to antihypertensive therapy capatina the patient was carried out test with sublingual introduction 25 mg of this drug by the method described above. After 30 minutes of taking the drug, the diameter of the upper temporal artery increased by 17.5%. This is a witness who was tovolo about the effectiveness of the drug, and he was assigned to the patient as an antihypertensive dose of 25 mg 3 times a day. Within 16 months, the patient was regularly attended capoten and the preparation was supported by an adequate level of blood pressure - 120-130/70-80 mm Hg, However, by the end of 16 months of taking the drug the blood pressure of the patient began to exceed the target value. It has been suggested the development of tolerance to capoten. With this purpose, the patient was re-performed test with sublingual taking 25 mg of capoten. As a result, the diameter of the upper temporal artery virtually unchanged (extension 3%), which helped confirm the presence of the patient's tolerance to this antihypertensive agent. Capoten the patient was replaced by cordaflex-retard 20 mg that the test caused an increase in the diameter of the upper temporal artery by 19%. The purpose of cordaflex-retard was accompanied by an adequate reduction in blood pressure to the target level.

Example 2.

Patient K., 78 years old, diagnosis: hypertension article III, ischemic heart disease myocardial infarction, N1.

Survey carried out by the above method pharmacological tests to the patient as an antihypertensive was selected drug enalapril 20 mg during the first dose of this drug increase the diameter of the upper temporal artery was 15%. The patient took the drug for 3 months with adequate antihypertensive effect. After 3 months from start of treatment the patient began to recorded episodes of blood pressure above the target level. To avoid development of tolerance re-test with amlodipine at a dose of 20 mg In the course of the marked increase in the diameter of the upper temporal artery 14% from the original. That allowed us to reject the assumption of tolerance to enalapril and testified unfavorable for arterial hypertension. Antihypertensive therapy has been strengthened with the appointment of 25 mg of hydrochlorothiazide, which in combination with taking enalapril 20 mg resulted in normalization of blood pressure for 4 days. After 21 days from the start of the reception of hydrochlorothiazide it was cancelled, and the patient continued monotherapy with enalapril 20 mg with adequate antihypertensive effect.

Example 3.

Patient R., 65 years, diagnosis: hypertension article III, ischemic heart disease, vasospastic angina, postinfarction cardiosclerosis, SSSU, N FL

For the implementation of individual selection of antihypertensive therapy, the patient was held pharmacological test with the aforementioned method with the drug cordipin-retard 20 mg Drug caused an expansion of the upper temporal artery n is 11% and was recognized as the original effective in a particular patient. The next day the patient was carried out test with drug amlodipine at a dose of 20 mg of the drug was also effective, and caused the increase in the diameter of the upper temporal artery 12%. As antihypertensive therapy, the patient was assigned to the combination of these drugs. Within six months of the combined intake of these drugs has been supported by the target level of blood pressure. After 6 months the average values of HELL reached the level of 160-170/100-110 mm Hg was an assumption of tolerance to take antihypertensive drugs.

For the purpose of diagnosis tolerance to the antihypertensive funds were held again pharmacological tests with drugs enalapril 20 mg and cordipin-retard 20 mg, which found that taking enalapril was still increased the diameter of the upper temporal artery (11%), while the purpose of cordipin-retard practically does not lead to any significant change in the diameter of the vessel. In this regard, the conclusion was made about the development of tolerance to cordipin-retard, while maintaining the effectiveness of enalapril. Cordipin-retard patient was canceled, and as antihypertensive therapy assigned to the combination of enalapril 20 mg and indapamide 2,5 mg Last during pharmacological tests expanded the diameter of the upper temporal Arte the AI is 11%. The new combination has allowed for the first week to reduce the level of blood pressure to target values.

The proposed method is:

1. Absolutely safe and does not cause complications from cardiovascular system.

2. No contraindications.

3. Highly reproducible and does not give false-positive and false-negative results.

4. To evaluate the effectiveness of antihypertensive drugs both short and long actions, regardless of the route of administration of the drug.

5. Gives the possibility to determine the degree of tolerance to the antihypertensive drugs - mathematically assessing the degree of loss of the pharmacodynamic effect of the drug.

Compared with the prototype method has the following advantages.

1. The method allows to evaluate the effectiveness of antihypertensive drugs of different groups, which significantly expands the scope of its application.

2. The method allows to reliably diagnose tolerance to the antihypertensive agents.

3. The method is more accurate and repeatable by specifying the name of the vessel and the level at which a reading is taken.

Method for diagnosis of tolerance to the antihypertensive drugs, including in the treatment process of examination, when the patient on whom Omak before and after the introduction of the medicinal product, at the time of the maximum of his actions, perform imaging of the fundus vessels and measuring the diameter of the retinal vessels, characterized in that when the increase in the diameter of the upper temporal branches of the Central artery of the retina at a distance of one vertical diameter of the optic disc from the edge of the optic disc by 10% or more from the source diagnose the effectiveness of the drug, and in the absence of increased diameter upper temporal branches of the Central artery of the retina by 10% or more on the introduction of identical doses of the drug to diagnose the development of tolerance to it.



 

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SUBSTANCE: invention relates to application of compound of formula I or II given below in preparation of medication for elimination or attenuation of microorganisms' growth in the way which includes subjection of said compound to exposure to source of light of photodynamic therapy or source of ultrasound of ultrasonic (sonodynamic) therapy, where X1, X2, X3 and X4 independently represent hydrogen atom, lipophylic part of molecule, phenyl group, lower alkyl, alkaryl or aralkyl group or cationic group of the following formula: -L-R1-N+(R2)(R3)R4 where: L represents binding (linking) part of molecule or is absent; R1 represents lower alkylene, lower alkenylene or lower alkinylene, which is optionally substituted with one or several substituents selected from lower alkyl, lower alkylene (optionally interrupted with oxygen), fluorine, OR5, C(O)R6, C(O)OR7, C(O)NR8R9, NR10R11 and N+R12R13R14; and R2, R3 and R4 independently represent H, aryl, lower alkyl, lower alkenyl or lower alkinyl, three latter of which are optionally substituted with one or several substituents selected from lower alkyl, lower alkylene (optionally interrupted with oxygen), aryl, OR5, C(O)R6, C(O)OR7, C(O)NR8R9, NR10R11 and N+R12R13R14; Z represents -CH or N; Y1, Y2, Y3 and Y4 are absent or independently represent aryl, lower alkyl, lower alkenyl or lower alkinyl, three latter of which are optionally substituted with one or several substituents selected from lower alkyl, lower alkylene (optionally interrupted with oxygen), aryl, OR5, C(O)R6, C(O)OR7, C(O)NR8R9, NR10R11 and N+R12R13R14, or, taken together with pyrrolic ring, to which they are bound, can form cyclic group; and R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 independently represent H or lower alkyl; M represents element of metal or metalloid; on condition that at least one of X1, X2, X3 and X4 is cationic group, defined above, and at least one of X1, X2, X3 and X4 represents hydrogen atom, phenyl group, lipophylic part of molecule or lower alkyl, alkaryl or aralkyl group, said microorganisms being selected from bacteria, mycoplasms, yeasts and/or fungi. Invention also relates to method of treating patient who needs treatment with antimicrobial agent and method of eliminating microorganisms in vitro, including contact of said microorganisms with compound of formula

and

EFFECT: novel application of porphyrin compounds as antimicrobial agent, said microorganisms being selected from bacteria, mycoplasms, yeasts or fungi.

67 cl, 13 dwg, 4 tbl, 7 ex

FIELD: medicine.

SUBSTANCE: pharmaceutical composition of fast release includes granules obtained by granulation from melt. Granules contain DPP-IV inhibitor and meltable hydrophobic component with ratio from 1:1 to 1:10 (per dry weight). At least 90% of granule surface are covered with meltable hydrophobic component. Granules release approximately 50% of DPP-IV inhibitor during 30 minutes after peroral introduction of medication. DPP-IV inhibitor is N-(substituted glicyl)-2-cyanopyrrolodin or its pharmaceutically acceptable salt. Preferably DPP-IV is (S)-1-[(3-hydroxy-1-adamantyl)amino]acetyl-2-cyanopyrrolidin.

EFFECT: composition for fast release according to invention possesses improved stability in presence of moisture in comparison with known compositions for controlled or prolonged release.

20 cl, 9 tbl, 10 ex

FIELD: medicine.

SUBSTANCE: pharmaceutical composition of fast release includes granules obtained by granulation from melt. Granules contain DPP-IV inhibitor and meltable hydrophobic component with ratio from 1:1 to 1:10 (per dry weight). At least 90% of granule surface are covered with meltable hydrophobic component. Granules release approximately 50% of DPP-IV inhibitor during 30 minutes after peroral introduction of medication. DPP-IV inhibitor is N-(substituted glicyl)-2-cyanopyrrolodin or its pharmaceutically acceptable salt. Preferably DPP-IV is (S)-1-[(3-hydroxy-1-adamantyl)amino]acetyl-2-cyanopyrrolidin.

EFFECT: composition for fast release according to invention possesses improved stability in presence of moisture in comparison with known compositions for controlled or prolonged release.

20 cl, 9 tbl, 10 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, oncology, and can be used for treating basaliomas. For this purpose dissection of affected skin portions is performed including healthy tissues within 0.5 cm by means of surgical laser with wavelength 810 nm pulse duration 0.2-0.5 seconds radiating power 15 W. After that 0.1% Radachlorin gel is applied on affected surface in terms 0.2 g per 1 cm2 of surface. 2-hour exposition under light-tight bandage. After gel removal surface is processed by laser light with wavelength 662 nm with light energy dose 200 J/cm2. Exposure is performed without contact. As laser radiation source, diode laser apparatus for photodynamic therapy "LAHTA-MILON" can be used.

EFFECT: method allows to prevent cosmetic defect, post-operation complications due to quick healing of affected area, stop of tumor growth of tissues, reduces method traumatism and number of recurrences.

2 cl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: described are water-soluble mono-PEGylated derivatives of tetrapyrrole of formulas (1A) or (2), (values of radicals Y,B,R1,R4-R6 are given in invention formula), pharmaceutical composition, containing them, method of obtaining compound (2), including interaction of corresponding tetrapyrrole of general formula (7) with aminopolyethyleneglycol of formula H-Y, containing functionalised end fragment.

EFFECT: application of novel compounds as photosensibiliser in photodynamic therapy.

5 cl, 2 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I: where A,Y,R and R2 assume values given in the description. The invention also relates to methods of producing compounds of formula I and their intermediate compounds, pharmaceutical compositions and methods of using the compounds and their pharmaceutical compositions for inhibiting caspase.

EFFECT: novel compounds have useful biological properties.

44 cl, 5 tbl, 66 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I: where A,Y,R and R2 assume values given in the description. The invention also relates to methods of producing compounds of formula I and their intermediate compounds, pharmaceutical compositions and methods of using the compounds and their pharmaceutical compositions for inhibiting caspase.

EFFECT: novel compounds have useful biological properties.

44 cl, 5 tbl, 66 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I: where A,Y,R and R2 assume values given in the description. The invention also relates to methods of producing compounds of formula I and their intermediate compounds, pharmaceutical compositions and methods of using the compounds and their pharmaceutical compositions for inhibiting caspase.

EFFECT: novel compounds have useful biological properties.

44 cl, 5 tbl, 66 ex

FIELD: chemistry.

SUBSTANCE: described are compounds of formula , where X, R1, R2, R3, R4 and R5 assume values given in the description and paragraphs of the formula of invention, and their pharmaceutically acceptable salts.

EFFECT: compounds have antagonistic activity on histamine receptor 3 (H3).

25 cl, 3 tbl, 215 ex

FIELD: medicine.

SUBSTANCE: invention can be used in ophthalmogeriatric practice for prediction of pseudoexfoliation syndrome (PES) arising, rate of its progression and determining indications for performing cataract extraction in due time. Method lies in determining index of eye ageing and if its value is more than 1.5 arising of quickly-progressing PES with development of 3 degree in terms up to 3 years from the momenr of arising is predicted, if values are 1.0-1.5 possibility of arising of slowly progressing PES, with development of 3 degree in terms longer than 3 years from the moment of arising, is predicted.

EFFECT: method allows to realise prediction of PES arising and rate of its progression.

2 ex

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