Method for preventing cardio-vascular diseases in women at climacteric period at the background of substitute hormonal therapy

FIELD: medicine.

SUBSTANCE: before applying substitute hormonal therapy (SHT) on should evaluate antithrombogenic activity of vascular wall in women. For this purpose one should determine quantitative values of ADP-induced aggregation of thrombocytes, activity of antithrombin III in blood and fibrinolytic blood activity both before and after "cuff"-test. Then one should detect the indices calculated as the ratio of mentioned values both before and after carrying out the mentioned test. If mentioned indices are decreased against the norm by 20-40% women should be prescribed to undergo SHT at additional introduction of aspirin and supradin. The method provides prophylaxis of cardio-vascular diseases in this category of female patients due to correcting affected functional activity of vascular endothelium.

EFFECT: higher efficiency of prophylaxis.

1 cl, 1 ex, 4 tbl

 

The invention relates to medicine and can be used when using hormone replacement therapy (HRT) in women with natural menopause.

The known method of prevention of cardiovascular diseases, including a comprehensive study of the mental status and spectral indices of HRV (EN 2195166 C1, publ. 27.12.2002).

The disadvantages of this method include the fact that it should not be the possibility of restoration of impaired functional activity of endothelium in patients with climacteric period on a background of hormonal replacement therapy (HRT).

Object of the invention is the correction of obvious violations of the functional activity of vascular endothelium in women in the menopausal period, the establishment of criteria for the selection of patients for conducting hormone replacement therapy, as the application of HRT possible thromboembolic complications.

The problem is solved in that in the method of prevention of cardiovascular disease before the use of hormone replacement therapy (HRT) assessing anti-platelet activity of blood vessels in women, this complex determine objective quantitative indicators antiaggregatory, anticoagulant and fibrinolytic activity wall with the courts using five-minute occlusion of the vessels of the forearm, caused by the imposition of the cuff of the sphygmomanometer on the shoulder of the subject (cuff test), then determine the indices of the anti-platelet activity of the vascular walls, which are calculated as the ratio of these indicators before and after the specified cuff samples, conduct a quantitative assessment of the degree of reduction of the anti-platelet activity of the vascular wall, in this case, if the specified index is lower than the norm in 20-40%of women prescribed HRT with the drug Divina (1 tablet a day) and parallel to this prescribed aspirin at a dose of 100 mg per day and Supradyn 1 capsule per day.

Preferably, the combination of aspirin and Spadina conducted throughout the period of the HRT courses for 90 days followed by a break of 180 days.

When using HRT possible thromboembolic complications. Restoration of impaired functional activity of endothelium in patients with climacteric period is a way of prevention of diseases of the cardiovascular and thromboembolic complications.

The main function of the endothelium is the anti-platelet activity of the vascular wall. Most women in menopause are detected deviation of anti-platelet activity of blood vessels from normative values due to estrogenic n is sufficiency. While HRT is an effective method of correction violated anti-platelet activity of the vascular wall only if it is a minor source reduction (not more than 20%). During the year, the normalization of indicators of anti-platelet activity of the vascular wall.

You can restore the anti-platelet activity of the vascular wall with its initial decline by 20-40%when HRT Divin (1 tablet once daily) in parallel with the use of aspirin at a dose of 100 mg per day and Supradyn 1 capsule per day. The combination of aspirin and Spadina should be conducted in parallel with HRT courses for 90 days followed by a break of 180 days.

The method includes the evaluation of anti-platelet activity of the vascular wall in women before therapy, the use of HRT in women with an initial decrease in anti-platelet activity of the vascular wall by more than 40% compared with the age norm leads to a further deterioration and development of diseases of the cardiovascular system associated with disorders of hemostasis. Such patients are prohibited HRT, as they have repeatedly (2-25 times or more) increases the risk of cardiovascular and thromboembolic complications (angina, heart attack, stroke, thromboembolism).

Anti-platelet activity of vascular stancioiu by defining an objective quantitative indicators antiaggregatory (ADP-induced platelet aggregation where ADP is the abbreviation of adenosintriphosphate), anticoagulant (activity of anti-thrombin III in the blood) and fibrinolytic (fibrinolytic blood activity) activity of blood vessels using the cuff of the sample according to the method Mavalue. Short-term (5 min) occlusion of the vessels of the forearm caused by the imposition of the cuff of the sphygmomanometer on the shoulder of the subject, leads to the release of the blood from the blood vessels healthy people plasminogen activator, antiaggregatory factor and anti-thrombin III.

Then determine the indices of the anti-platelet activity of the vascular wall, calculated as the ratio of the above indicators before and after cuff samples, conduct a quantitative assessment of the degree of reduction of the anti-platelet activity of blood vessels using the specified index.

A specific example of the method

Were surveyed 180 women aged 46-48 years. All women were diagnosed with diabetes mellitus type 2 moderate compensation stage amid menopausal syndrome of varying severity. All women were identified reduced anti-platelet activity of the vascular wall from the specified values by more than 20%. Surveyed women received hormone replacement therapy drug Divina (oral, 1 pill a day, Kale is shock package 21 days, 7 days break) and oral hypoglycemic therapy drug siofor (500 mg 2 times a day), as well as drugs: aspirin cardio (1 tablet (100 mg) daily) and Supradyn (1 tablet daily) for 3 months with a 6 month break. Women were observed during the 3 years, with periodic monitoring of anti-platelet activity of the vascular wall after 1 month, then every 3 months. As a control, we examined 40 healthy women of reproductive age in the age 42-44 years.

All women were examined to identify gynecological and extragenital pathology. None of the patient was not observed in cases of decompensated diabetes. For various reasons from the proposed therapy, 15 patients refused.

Statistical processing of data was performed using ANOVA statistical Microsoft programs (Excel).

The results obtained after the first year of therapy, has facilitated the sharing of women surveyed into two groups: group a (n=100 per treatment was effective (smfbl), in group b (n=80 pax) - no (table 2). Study of the results showed that the effectiveness of therapy depends on the source of violations of the anti-platelet activity of the vascular wall and critical is the change in the indices comprising antithrombogenic the activity of the vascular wall, 40%. In women with source reduction anti-platelet activity of the vascular wall is not more than 40% (group a), the use of the above drug combination led to a normalization of its performance after 3 months of therapy (table 1). In the case of a more pronounced reduction of functional activity of the vascular wall (group b), despite ongoing therapy, indicators of anti-platelet activity remained at baseline (table 2).

As follows from the presented data in table 3, anti-platelet activity of the vascular wall in women in the group And remained within normal values over the next 2 years of observation, while none of the women was not recorded diseases of the cardiovascular system.

In table 4 presents the dynamics of the anti-platelet activity of the vascular wall in women group C. these women over the next 2 years of observations there was a further reduction in anti-platelet activity of the vascular wall by 3-5%. On the background of the above changes in the functional activity of vascular endothelium in 8 women are diagnosed with a myocardial infarction, 4 - stroke, 32 - angina, 3 - embolism.

Thus, hormone replacement therapy in combination with aspirin and Spadina applied every 90 days with 180-day clause is rarawa, is an effective method for correcting anti-platelet activity of the vascular wall in women in the menopausal period when the source reduction of 20-40%.

Table 1
The dynamics of anti-platelet activity of the vascular wall under the influence of therapy Divin, aspirin and Spadina in group a during the first year of observation
IndexControl-eThe source dataThe duration of therapy (months)
(index)group 136912
ATIII,1,28± 0,041,01± 0,061,07± 0,061,27± 0,111,27± 0,121,26± 0,101,27± 0,11
FAK, %1,56± 0,051,12± 0,071,21± 0,041,57± 0,041,56± 0,031,56± 0,011,56± 0,04
ADP-induced platelet aggregation, %0,82± 0,041,11± 0,061,06± 0,050,83± 0,8 0,84± 0,040,84± 0,050,82± 0,07
Table 2
The dynamics of anti-platelet activity of the vascular wall under the influence of therapy Divin, aspirin and Spadina in group b during the first year of observation
IndexControl-eThe source dataThe duration of therapy (months)
(index)group 136912
ATIII,1,28± 0,040,70± 0,040,71± 0,050,71± 0,040,75± 0,060,90± 0,060,91± 0,05
FAK, %1,56± 0,050,81± 0,050,81± 0,050,84± 0,050,84± 0,060,86± 0,060,85± 0,06
ADP-induced platelet aggregation, %0,82± 0,041,23± 0,041,24± 0,071,24± 0,041,21± 0,041,22± 0,051,21± 0,05

Table 3
The dynamics of anti-platelet activity of the vascular wall under the influence of therapy Divin, aspirin and Spadina in group a during 3 years of follow-up
Index (index)The duration of therapy (years)
 123
AIII,1,27±0,111,28±0,101,27±0,12
FAK, %1,56±0,041,55±0,031,57±0,06
ADP-induced platelet aggregation, %0,82±0,070,81±0,040,82±0,06
Table 4
The dynamics of anti-platelet activity of the vascular wall under the influence of therapy Divin, aspirin and Spadina in the group during 3 years of follow-up
Index (index)The duration of therapy (years)
 123
ATIII,0,91±0,050,72±0,070,65±0,07
FAK, %0,85±0,060,83±0,030,76±0,04
ADP in osirovna platelet aggregation %1,21±0,051,23±0,031,27±0,05

1. Method of prevention of cardiovascular disease in women in the menopausal period on a background of hormonal replacement therapy (HRT), characterized in that before HRT investigate anti-platelet activity of the vascular wall, defining indicators of ADP-induced platelet aggregation, activity of anti-thrombin III in the blood and fibrinolytic activity of the blood and the relationship of these indicators before and after “cuff test”, and when the indices that reflect these relationships by 20-40% in comparison with the norm, it is also prescribed aspirin at a dose of 100 mg per day and Supradyn 1 capsule per day.

2. The method according to claim 1, characterized in that the combination of aspirin and Spadina carried out throughout the period of the HRT courses for 90 days followed by a break of 180 days.



 

Same patents:

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to a group of new derivatives of 4,5-dihydro-1H-pyrazole of the general formula (I):

wherein R means phenyl, thienyl or pyridyl and these indicated groups can be substituted with (C1-C3)-alkoxy-group or halogen atom; R1 means phenyl that can be substituted with (C1-C3)-alkoxy-group or pyridyl group; R2 means hydrogen atom or hydroxy-group; Aa means one group among the following groups: (i) , (ii) , (iii) , (iv) or (v) ; R4 and R5 mean independently from one another hydrogen atom or (C1-C8)-branched or unbranched alkyl; or R4 means acetamido- or dimethylamino-group or 2,2,2-trifluoroethyl, or phenyl, or pyridyl under condition that R5 means hydrogen atom; R6 means hydrogen atom at (C1-C3)-unbranched alkyl; Bb means sulfonyl or carbonyl; R3 means benzyl, phenyl or pyridyl that can be substituted with 1, 2 or 3 substitutes Y that can be similar or different and taken among the group including (C1-C3)-alkyl or (C1-C3)-alkoxy-group, halogen atom, trifluoromethyl; or R3 means naphthyl, and its racemates, mixtures of diastereomers and individual stereoisomers and as well as E-isomers, Z-isomers and mixture of E/Z-compounds of the formula (I) wherein A has values (i) or (ii), and its salt. These compounds are power antagonists of Cannbis-1 (CB1) receptor and can be used for treatment of psychiatric and neurological diseases. Except for, invention relates to a pharmaceutical composition used for treatment of some diseases mediated by CB1-receptor, to a method for preparing this composition, a method for preparing representatives of compounds of the formula (I) wherein Aa means group of the formulae (i) or (ii), intermediate compounds used for preparing compounds of the formula (I) and to a method for treatment of some diseases mediated by CB1-receptor.

EFFECT: valuable medicinal properties of compounds.

16 cl, 9 ex

FIELD: organic synthesis.

SUBSTANCE: invention provides compounds of general formula I:

, where R1 represents -CO-Ra, -SO2-Rb, or aryl optionally substituted by lower alkoxy, wherein Ra represents cycloalkyl, cycloalkyl(lower)alkyl, cycloalkyloxy, aryl, aryloxy, aryl(lower)alkyl, aryl(lower)alkoxy, aryloxy(lower)alkyl, aryl-S-(lower)alkyl, aryl(lower)alkenyl, provided that aryl group can be optionally substituted by halogen, lower alkyl, hydroxy, nitro, cyano, lower alkoxy, phenyl, CF3, cyano(lower)alkyl, lower alkyl-C(O)NH, lower alkyl-CO, and lower alkyl-S; heteroaryl, heteroaryl(lower)alkyl, or heteroaryl(lower)alkoxy, provided that heteroaryl group is 5- or 6-membered ring or bicyclic aromatic group constituted by two 5- or 6-membered rings including 1-3 heteroatoms selected from oxygen, nitrogen, and sulfur and that heteroaryl group can be optionally substituted by lower alkoxy; Rb represents aryl, aryl(lower)alkyl, or heteroaryl, aryl group optionally substituted by halogen, cyano, or lower alkyl-C(O)NH; R2 and R3 represent hydrogen atoms; R4 representshydrogen or lower alkyl; R5 represents hydrogen, lower alkyl, cycloalkyl, benzodioxyl, or aryl optionally substituted by lower alkyl, halogen, lower alkoxy, hydroxy, or (lower)alkyl-C(O)O; n is 1 or 2; and pharmaceutically acceptable salts thereof and/or pharmaceutically acceptable esters thereof. Invention also provides a pharmaceutical composition exhibiting inhibitory activity with regard to cysteine proteases of the cathepsin family, which composition comprises compound of formula I, pharmaceutically acceptable recipient, and/or adjuvant.

EFFECT: increased choice of cysteine protease inhibitors.

34 cl, 1 tbl, 13 ex

FIELD: medicine, cardiology.

SUBSTANCE: it is suggested to apply cortisol antagonists in addition to clonidine while manufacturing preparation to treat heart failure. Moreover, one should introduce cortisol antagonist or a product that includes cortisol antagonist along with the second medicinal preparation being a combined preparation to be applied either simultaneously, separately or successively. The present innovation provides decreased symptoms of heart failure at decreasing cardiac muscle's fibrosis and heart sizes due to preferable impact upon glucocorticoid receptors in patient's heart and/or kidneys.

EFFECT: higher efficiency of application.

12 cl, 2 ex

FIELD: medicine.

SUBSTANCE: method involves administering Noliprelum in postoperative period for reducing left ventricle hypertrophy.

EFFECT: enhanced effectiveness of treatment in early postoperative period.

FIELD: medicine.

SUBSTANCE: method involves administering Noliprelum in postoperative period for reducing left ventricle hypertrophy.

EFFECT: enhanced effectiveness of treatment in early postoperative period.

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to synthesis of new biologically active substance, namely, to γ-hydroxypropylammonium-5-hydroxynicotinate of the formula (I): , eliciting an anti-ischemic, anti-arrhythmic and hypolipidemic activity. This compound shows low toxicity and absence of cardiodepressive effect. Compound of the formula (I) is prepared by interaction of 5-hydroxynicotinic acid with 3-amino-1-propanol in the presence of a solvent at heating.

EFFECT: valuable medicinal properties of compound.

1 cl, 7 tbl, 3 ex

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to synthesis of new biologically active substance, namely, to γ-hydroxypropylammonium-5-hydroxynicotinate of the formula (I): , eliciting an anti-ischemic, anti-arrhythmic and hypolipidemic activity. This compound shows low toxicity and absence of cardiodepressive effect. Compound of the formula (I) is prepared by interaction of 5-hydroxynicotinic acid with 3-amino-1-propanol in the presence of a solvent at heating.

EFFECT: valuable medicinal properties of compound.

1 cl, 7 tbl, 3 ex

FIELD: medicine, cardiology.

SUBSTANCE: traditional therapy of myocardial infarction should be supplemented with granocyte introduced either subcutaneously or intravenously at the dosage of 0.48 mln IU/kg body weight daily for 5 d.

EFFECT: higher efficiency of therapy.

2 ex

FIELD: medicine, cardiology.

SUBSTANCE: patient with stenocardia should be introduced with efficient quantity of omapathrylate or its pharmaceutically acceptable salt either separately or in combination with another pharmaceutically active agent. Another pharmaceutically active substance could be represented by organic nitrate, beta-adrenergistic blocking agent, blocking agent of calcium supply or antithrombocytic preparation. It is suggested to apply omapathrylate or its pharmaceutically acceptable salt to prepare medicinal preparations for treating and/or decreasing stenocardial symptoms.

EFFECT: higher efficiency.

16 cl, 2 dwg, 2 ex, 8 tbl

FIELD: medicine, combustiology, resuscitation.

SUBSTANCE: during the first 2 d since the moment of trauma one should intravenously inject infusion solution of vasaprostan additionally to conventional anti-shock therapy at 1 mcg/kg patient's body weight daily. The present innovation favors to normalize capillary walls' tonicity, decrease their permeability and improve the values of blood hemoconcentration and viscosity.

EFFECT: higher efficiency of correction.

1 ex, 1 tbl

The invention relates to medicine and refers to the treatment and prevention of normalizing the functions of the genital organs, acute amenorrhea, neurological development and osteoporotic manifestations in premenopausal or menopausal periods

The invention relates to the field of medicine and relates to self-adhesive drug composition for percutaneous use of estrogen combined with progestogen containing 25-90 wt.% self-adhesive acrylate copolymer, 1-15 wt

The invention relates to medicine, in particular to the pharmaceutical industry for the production of drugs therapeutic and prophylactic purposes, and can be used as a means to reduce the risk of symptoms of menopausal syndrome
The invention relates to medicine and for new ways of correction of oestrogen deficiency in natural or artificial menopause
The invention relates to medicine, gynecology, and can be used for the treatment of menopausal syndrome

The invention relates to new naphtylpropionate F.-ly (I), where R1and R2- N, -HE or-O(C1-C4-alkyl); R3- 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholinyl, dialkylamino - or 1-hexamethylen-aminogroup; n = 2 or 3, or pharmaceutically acceptable salts

The invention relates to new niftystories compounds of formula I, where R1and R2- H, -OH, -O(C1-C4alkyl), -OCOC6H5, -OCO(C1-C6alkyl), -OSO2(C4-C6alkyl); R3- 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, 1 hexamethyleneimino; intermediate compounds, which are suitable for easing symptoms of postmenopausal syndrome, including osteoporosis, hyperlipemia and estrogenzawisimy cancer, and inhibition of uterine fibroids, endometriosis and proliferation of aortic smooth muscle cells

FIELD: medicine, oncology.

SUBSTANCE: the present innovation deals with treating patients with uterine cervix cancer with relapses in parametral fiber and in case of no possibility for radical operative interference and effect of previous radiation therapy. During the 1st d of therapy one should intravenously inject 30 mg platidiam incubated for 1 h at 37 C with 150 ml autoblood, during the next 3 d comes external irradiation per 2.6 G-r. During the 5th d of therapy one should introduce the following composition into presacral space: 60 ml 0.5%-novocaine solution, 1 ml hydrocortisone suspension, 2 ml 50%-analgin solution, 1 ml 0.01%-vitamin B12 solution, 1.6 g gentamycine, 800 mg cyclophosphan, 10 mg metothrexate. These curative impacts should be repeated at mentioned sequence four times. The method enables to decrease radiation loading and toxic manifestations of anti-tumor therapy at achieving increased percent of tumor regression.

EFFECT: higher efficiency of therapy.

1 ex

Up!