Method of treating benign hyperplasia of prostate gland

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to urology, and can be used for treatment of benign hyperplasia of prostate gland. For this purpose dynamic examination of prostate gland is carried out before drug therapy and 3, 6 and 9 months after that. Dynamic examination includes transrectal ultrasound examination (TRUSE) with Dopplerography and sonoelastography (SEG) of prostate gland. Comparison of prostate size values, hyperplasia size, blood flow in capsular and parauretral arteries, blood flow in adenomatous nodes and density of transitory zones of prostate is carried out in SEG. If values of examined parameters by TRUSE data decrease by 15% and more, each parameter is given 1 point. If density of transitory zones of prostate in sonoelastography is higher than 35 KPa, 1 point is given too. As a result if the sum is not less than 4 points, conservative therapy is stopped. If the sum of points is less than 4 points, therapy is continued. Examination is repeated after next 3 months.

EFFECT: method ensures reduction of terms of drug treatment and increase of treatment quality due to possibility of determining indications for complete or partial cancellation of drug treatment within 3-6 months.

1 tbl, 3 ex

 

The invention relates to medicine, namely to urology, and can be used for the treatment of patients with benign prostatic hyperplasia (BPH).

Benign prostatic hyperplasia (BPH) is a progressive condition characterized by enlargement of the prostate (PI) and with symptoms of lower urinary tract (SNMP). Approximately 75% of men over age 50 have symptoms resulting from BPH, and 20-30% of men 40 years of age, under the age of 80 years of life will require surgical intervention for BPH (Gasanova VE New ultrasound technology in the diagnosis and monitoring of treatment of diseases of the prostate". Diss. Doc. the honey. Sciences. 2002).

Currently, BPH is the most common illness among men older than 50 years (L.A. Mitin, V. Kazakevich, S.O. Stepanov. Ultrasonic oncourology. Ed. by V.I. of Cassova, I.G. Rusakova. Moscow, 2005, 200 C., with Illus.).

The progression of BPH is manifested in the strengthening of disorders of urination, worsening quality of life, increasing the risk of acute urinary retention (AUR) and the need for surgery (Zubarev A. Ultrasound assessment of the vascular pattern of the prostate gland in normal and adenoma / ALEXANDER Zubarev, V.E. Gasanova // Visualization in the clinic. - 1997. No. 11. - P.35-43).

Despite the development of techniques of surgical interventions, the number of postoperative complications remains high. The total number of immediate postoperative complications (14.5%) and complications in the long term (16,7%) after ROUND mud reaches to 31.2%, and after crespuzyrna adenomectomy - 35, 85% (Transrectal sonography in patients with diseases of the prostate. YG alyayev, A. Amosov, AS Vinarov, K.L. Church, G. Spivak. - National publishing house "Kostroma", 2004. - P.88).

Thus, an important direction for BPH treatment is the improvement of methods of conservative therapy of the disease.

To assess intra - and blood flow in the prostate gland are ultrasonic methods, as color Doppler mapping, power Doppler mapping, three-dimensional reconstruction of the mode energy mapping, ultrasound angiography (CE Alexandrov, M.I. Karelin 2004). A promising direction in the diagnosis of neoplastic lesions of the prostate is sonoelastography (Gasanova V.E. 2002).

Medical treatment according to the recommendations of EAU involves applying only drugs from the group of inhibitors of 5-α reductase and α blockers. In recent decades, medical treatment was so effective that in most patients the question about surgical treatment is deposited on opredelennoe time Ultrasound imaging in the diagnosis of prostate cancer. V.N. Sholokhov, BV Bukharin, P.I. Lepadatu, 1st edition - M.: OOO "firma STROM", 2006. - 112 S.: ill.).

Thus, it can be stated that currently, the following methods are used for the treatment of BPH.

I. follow the advice of an expert

II. Medication

a) Effect on efferent link autonomic nervous system:

competitive inhibition of 1-adrenergic receptors of the bladder neck and prostatic Department urethra selective ganglioblokatorami. Used 1-adrenergic blockers: doxazosin, terazosin, alfuzosin etc.) (Christian de Mey. The alpha-blockers in treatment of BPH: whether there are distinctions? Eur Urol - 1999; 36 (suppl-3): P.52-63); Vinarov AS // Drug treatment prostatic hyperplasia. - Diss...Doc. the honey. Sciences. - M - 1999. - P.1-349);

competitive inhibition of M-acetylcholine receptors in the detrusor (oxybutynin, tolterodine) (Savchenko N.A. et al. // Non-surgical methods of treatment of BPH. - Minsk. - 1998).

b) Competitive inhibition of 5-reductase inhibitor (Finasteride) (O. Laurent, etc. // Comparative evaluation of effektivnosti and safety of combination drug therapy in patients with benign prostatic hyperplasia drugs Finasteride and Alfuzosin. - Urology. No. 1. - 2002).

in Therapy herbal remedies (SV Minds, I.I. Derevyanko, A.V. Sivkov // Prostamol-DNA in the treatment of Bo is lnyh with benign prostatic hyperplasia. - Urology. No. 2. - 2001. - P.35-37).

III. Surgical treatment

a) Radical or palliative removal of adenomatous nodes (partial prostatectomy, TURP operation), (A.G. Martov and other Transurethral retortable in the treatment of BPH. - Urology. No. 4. - 2000).

b) minimally Invasive treatment methods:

endoscopic thermal methods: interstitial laser coagulation of the prostate; TUNA (transurethral needle ablation of the prostate; prostatic stents (A. I. Kornev, GI Varentsov. Laser technologies prostate surgery. - Urology and Nephrology. No. 2. - 1996, 49-52; became popular Dolgopyatova, A.S. Segal, L.V., Ciganko. Transurethral radiofrequency thermotherapy using the apparatus of Termex" in an accident. - Urology and Nephrology. No. 6. - 1995. - P.48-50);

- endoskopicheskie thermal methods: transrectal microwave hyperthermia; transurethral microwave (or RF) therapy; transurethral radiofrequency thermal decomposition of the prostate; - transrectal focused ultrasound thermoablative prostate; extracorporeal pyrotherapy prostate; balloon dilatation of the prostate (Benign prostatic hyperplasia. Edited by Lopatkin N.A. M 1997);

- cryosurgery;

one of the new technologies in surgery BPH is electrovaporization, based on the effect of the issue is the air traffic management of prostatic tissue special roller electrode under the influence of the current high power (V.M. Nagorno and other Combined andelectronically treatment of benign prostatic hyperplasia, 2000).

It should be noted that all of these methods are different sclerosing hyperplastic nodes of the prostate (laser, thermal, high frequency, cryosurgery) with the substitution later in this zone robovie tissues and, thereby, increase the lumen of the prostatic urethra.

Criteria of treatment efficacy are the dynamics of the IPSS, the reduction of prostate volume, maximum urinary flow rates (Q max), residual urine volume and PSA.

There is a method of monitoring treatment of prostate tumors by RF patent No. 2079132 (10.05.1997), including a preliminary detection of the disease by determining the DNA content in tumor cells of the biological material. The method is characterized by the fact that, as the use of biological material of the morning urine before and after digital examination of the prostate gland (IF), and if it finds it after WHEN increasing the number of cells with DNA content greater than tetraploid and/or more than 5-7 number of cells with DNA content greater than that of normal diploid, compared with a sample of urine to IF, judged on the presence of the tumor cells of the prostate. Follow-up treatment made tlaut to change these parameters, in this case, the decrease in their value judgments about the correctness of the chosen course of treatment.

The disadvantage of this method is to accelerate the detection of tumor cells and reducing the morbidity of the procedure, but is only applicable in Oncology. As pointed out by the authors themselves, a comparative analysis of the percentage of cells in G0 and G1 phases of the cycle and elements with ploidy less than 20, shows that the performance of the group of patients with adenomas and cancer of the prostate, differ little from each other, although different from control (p<0,05).

There is a method of treatment of BPH by the RF patent №2124314 (10.01.99), according to which conduct clinical and instrumental examination of the patient, record the social indicators: age, presence of comorbidity, assess the quality of life, time loss disability, the nature of the employment activity after treatment. Evaluate the performance instrumental examination: the mass of the prostate gland, the amount of residual urine, the nature of the scar-sclerotic changes in the prostate gland, metric flow rate of urination, character growth lobes of the prostate, the coefficient of expansion of the bladder muscles. Determined by Trembley scale rate health and choose depending on coefficie is the conservative treatment, laser ablation of the prostate, transurethral resection of the prostate, adenomectomy.

The disadvantage of this method is the difficulty of defining and evaluating a large number of factors that may affect its accuracy.

There is a method of treatment of BPH by the RF patent №2167687 (27.05.2001) method visual laser ablation. Each patient before treatment individually select the exposure dose of laser irradiation. To do this, hold the patient survey, which are determined by: the type of growth lobes of the prostate, the weight of the prostate gland, the degree of sclerosing prostate cancer, the average volumetric rate of urination, the maximum power of contraction of the detrusor and the reactivity of the organism to laser treatment. Using the figures obtained by the formula N=Nmax[1] [2] [3] ([4] [5] and [6]), calculate the optimal exposure dose of laser irradiation.

The disadvantage of this method: a large amount of parameters, invasiveness, the probability of relapse, the absence of histological control.

There is a method of determining the treatment of patients with benign prostatic hyperplasia by RF patent No. 2205001 (27.05.2003), consisting in the execution of uroflowmetry, characterized in that the re-uroflowmetry spend 2 weeks after administration of 1-blocker, e.g. the Tamsulosin, and in case of improvement of urodynamic indices continue medical therapy, and in case of deterioration - designate of surgical treatment.

The disadvantage of low efficiency method uroflowmetry, the possibility of a sharp decline in blood pressure in the patient. In addition, 1-blocker only affects receptors in smooth muscles, i.e. irritative symptoms.

Described is a method of treatment of BPH by assigning dutasteride, if this is considered a minimum term of appointment of dutasteride 6 months (Kogan M.I. Clinical case of benign prostatic hyperplasia. RMJ. Tom 19, №16 (410), 2011). The criterion of effectiveness of the drug, according to the author, are the data of transrectal us, which is the source before therapy and after 6 months of treatment.

The disadvantages of this method: the lack of an integrated approach to the use of transrectal us (Doppler, assessment of blood flow in adenomatous nodes, sonoelastography).

The prototype of the invention, the selected method of treatment of benign prostatic hyperplasia (BPH) patent of Russian Federation №2250748 (27.04.2005), which consists in performing urodynamic examination and prescription of pharmaceuticals, characterized in that exercise excretory cystometry with simultaneous registration of the total amplitude of the action potential motor is of Diniz (SPDE) muscles of the perineum and external anal sphincter by means of surface electrodes and, in case of confirmation of obstructive voiding according to the excretory cystometry and identify improvement total amplitude SPDE more than 500 µv, the patient is prescribed a muscle relaxant Central mechanism of action tizanidine dose of 24 mg per day in three doses (8 mg three times a day).

The disadvantage of the prototype method is the complexity and invasiveness of the study.

The present invention is the reduction of the period of medication and increase its effectiveness in patients with BPH by performing transrectal ultrasound transrectal us) and detect (SAG) with subsequent determination of the indications for continuation or cessation pharmacotherapy.

This task is solved in that the dynamic survey carried out by the methods of transrectal ultrasound transrectal us) with Doppler and detect (SAG) prostate gland, conduct a comparison of the values of the size of the prostate size, prostate hyperplasia, blood flow in the capsular (PKA) and paraurethral arteries (PUA), blood flow in adenomatous nodes and density of transient zones of the prostate at SAG to drug therapy dutasterida in the dosage of 0.5 mg 1 time per day and tamsulosin dosage of 0.4 mg 1 time per day, and after 3, 6, 9, etc. months after it, and, if the values the analyzed parameter is in according to the transrectal us decrease by 15% or more - for each indicator is scored 1 point, if the density of transient zones of the prostate when detect exceeds 35 KPa - 1 point, if the amount is not less than 4 points cease conservative therapy. If a score of less than 4, CT and continue the study may be repeated in the next 3 months.

The technical result obtained from applying the proposed method for the treatment of BPH, is that this method allows for 3-6 months to determine the indications for full or partial cancellation of medical treatment of BPH, which improves the quality of treatment, while the prolongation of pharmacotherapy leads to expensive and unnecessary delay in treatment, increasing drug load on the patient's body. The term of 3.6 months due to the fact that the control in a shorter time dynamics of the investigated parameters PJ is not clear.

Arterial blood is delivered to the prostate paired prostatovesiculitis arteries (branches of the internal iliac arteries), are divisible into two terminal branches: prostatic and lower the cystic artery. Prostatic artery gives rise to two groups of blood arteries: capsular and urethral uniformly distributed on the gland (M.I. Kogan et al. 2011).

The main arteries involved in the blood supply of the prostate include: capsular, idealnie and urethral (Pereverzev A.S. 2004; Orozmambetova AH 1999; alyayev YG et al 2004; MG weight Gain 1974). For normal vascular pattern of the prostate gland characterized by symmetry, the absence of focal or diffuse changes, keeping the normal pace and size of individual vessels (alyayev YG et al. 2004).

Thus, the main inflow of arterial blood provides capsular group of prostatic arteries. These vessels passing in the parenchyma of the prostate, Oxygenium more than two thirds of prostatic tissue. Therefore, any processes, leading to reduced blood flow in prostatomegaly and parenchymal blood vessels (compression, the reduction in internal diameter), can lead to the development of tissue hypoxia prostatovesical segment that produces the clinical picture of pain, impaired urination and ED (M.I. Kogan et al. 2011).

When performing the mud transrectal us in healthy men can visualize anatomical four glandular zone (Central, peripheral, and two transient) and four fibromuscular layer (front massive fibro muscular stroma, prepostericity and postprostatectomy sphincter, longitudinal smooth muscles of the urethra (McNeal J.E. 1981, 1983; YG alyayev, 2009; VN Sholokhov et al. 2006).

The volume of mud is one of the least dependent on the subjective errors of the indicators. Often su is th in clinical practice it is calculated by the formula V=0,52×D×W×h (where D, W and the size of the prostate in three dimensions). In normal conditions it does not exceed 30 cm cubic (Gasanova V.E. 2002).

It is believed that in the study of unmodified prostate mode, spectral Doppler characterization of blood flow is possible in all rendered with a color/energy mapping arteries and veins (ALEXANDER Zubarev, V.E. Gasanova, 1997; YG alyayev et al, 2004).

Normal indicators of maximum systolic velocity of blood flow in the prostate gland: from 4.5 to 11 cm/s for urethral arteries and from 8 to 17 cm/s for capsular (Gasanova V.E. 2002; ALEXANDER Zubarev, V.E. Gasanova, 1997; A.I. Gromov, 1999).

In normal mud no statistically significant difference between the blood flow values of the different anatomical areas (YG alyayev et al. 2004).

Data linear velocity of blood vessels in the mud difficult to assess, as their calculation is unreliable due to the small duration visualization of the vessel, its small diameter (about 0.1 cm) and the complexity of spatial location within the prostate gland. These reasons do not allow you to adjust the angle of the Doppler scan, which inevitably leads to significant errors in the measurement results and a low reproducibility of the data.

In the Aixplorer system for the first time in the ultrasonic diagnosis function is applied, the issue is rastvornogo composite ultrasonic scanning using computer technology to obtain the highest quality image with color Doppler mapping or energy the Doppler examination.

In the available literature we have not identified the study of changes in ultrasound hemodynamic picture of the prostate gland in different modes of conservative therapy (CT)to determine a criterion of its efficiency at any stage of treatment. Also there are no data on the use detect to study in the dynamics of changes in the mud under the influence of CT. Technology ShearWave gives you the opportunity to receive objective elastographic image, where each pixel of the image may be separately processed, regardless of the nature of the surrounding tissue. Elastography ShearWave makes it possible to objectively evaluate in numerical terms, the local elasticity of the fabric and does not rely on the method of manual compression, so the obtained results are consistent and reproducible in the future. There is the opportunity to compare and track area, causing the interest for a certain period of time, while getting a numerical parameters. This provides additional reliability in the diagnosis and shows objective results. Aixplorer produces an image, called elastography card. It demonstrates the elasticity or density of the fabric in the color coding. The elasticity of the tissue is quantitatively determined on the basis of the velocity of propagation in the village of the Whigs waves. On the basis of the well-known modulus of elasticity young's modulus, the elastic fabric can be defined as the velocity of propagation of sound waves are measurable. Using Q-box can be measured any pixel of visual information in the targeted treatment area during subsequent surveys. The propagation velocity of shear waves depends on the degree of elasticity of the investigated tissue. This dependence can be expressed quantitatively in kilopascals. In the actual elasticity of the fabric of the study area, expressed in kilopascals, is displayed using color mapping, along with the usual visual information in the form of In-image. Map with color coding shows a dense fabric of high in kilopascals, in red colour scheme. Upholstered fabric low in kilopascals depicted in blue colour scheme. The Q-Box it is possible to measure the elasticity of tissue in kilopascals in any area and elasticity of the fabric one specific area. Using the second Q-Box, you can measure the density of the other and compare them.

Thus sonoelastography ShearWave (Shear Waves) gives the possibility to evaluate in numerical terms, the local elasticity of the fabric. The elasticity of the fabric is alicantino is determined based on the velocity of propagation in her shear waves. The propagation velocity of shear waves depends on the degree of elasticity of the investigated tissue. This dependence can be expressed quantitatively in kilopascals. In the actual elasticity of the fabric of the study area, expressed in kilopascals, is displayed using color mapping, along with the usual visual information in the form In the image.

These regulations formed the basis of our research with the aim of obtaining objective measures of abolition of the medication.

Dutasteride, affecting the hyperplastic prostate tissue, indirectly, through suppression of the activity of the isoenzymes of 5-α reductase type 1 and 2, causes it to atrophy. Atrophy of the tissue leads to a reduction of prostate volume and the hyperplasia, decrease rate and blood flow and increase the density of tissue (defined using detect). Thus the positive dynamics of changes in the size of prostate hyperplasia, blood flow in the capsular (PKA) and paraurethral arteries (PUA), blood flow in adenomatous nodes. The combination of these factors results in remission of the disease, allowing you to undo conservative therapy.

Detailed description of the method and examples of its clinical implementation

For conservative combined treatment of BPH who were Tbilisi patients no absolute indications for surgery such as bladder stone; recurring hematuria; not permitted conservatively acute urinary retention; bilateral ureterohydronephrosis; chronic renal failure. Contraindications to therapy were also considered to be the refusal of a patient from conservative treatment.

Before drug therapy dutasterida in the dosage of 0.5 mg 1 time per day and tamsulosin dosage of 0.4 mg 1 time per day shall study mud methods transrectal ultrasound transrectal us) and detect (SAG) of the prostate. Use the Apparatus Aixplorer SSIP 90089 system MultiWave and endocavitary sensor 12-3 MHz, firm Su-perSonic Imagine, France.

With the patient lying on your side with your knees bent perform transrectal study to assess the prostate gland (PI) in b-mode. Examine the shape, contour, symmetry shares mud, zonal characteristics, the degree of differentiation of zones, the presence of focal lesions zones with a detailed description of the structural characteristics of the "hearth" and secondary changes in it. Then evaluate the transient area, volume, presence of hyperplasia, hyperplastic volume zones; periuretralnuu cancer, the presence of hyperplasia; boundary layer gland; seminal vesicles, their structure, symmetry, size is s, the presence of focal lesions; the projection of the seed tubercle and samovyravnivayuschie ducts. Perform ultrasound angiography prostate mode energy mapping, evaluate its vascular pattern in the whole, its symmetry, the severity, the type of vascular pattern, the presence of zones of deformation as a whole and individually. When color Doppler mapping expect speed and spectral characteristics of blood flow in the capsular and paraurethral vessels, as well as in areas of hyperplasia of both sides of (Vmax, Vmin), and the characteristics of blood flow in abnormal sites. If detect (SAG) estimate the density of the peripheral zones at two points on symmetric sections (left and right lobes); the density of transient zones of the gland on the symmetric parts of at least 3 points on both sides; take the average density of transient zones.

Parameters evaluated according to 5 criteria:

1. The size of the prostate

2. The size of the prostate hyperplasia

3. The blood flow in PKA and POIX

4. The blood flow in the adenomatous nodes

5. The density of transient zones of the prostate at SAG

Record the data. Patients prescribed combination of conservative therapy: dutasteride at a dose of 0,5 mg 1 time per day and tamsulosin 0.4 mg 1 time a day, constantly.

About anywayt dynamics parameters measured again after 3, 6, 9, etc. months. The criterion for the termination of conservative therapy in patients is the sum of not less than 4 points:

1. Decreased prostate according to the transrectal us by 15% or more - 1 point;

2. Decreased hyperplasia according to the transrectal us by 15% or more - 1 point;

3. Decreased blood flow in PKA and POIX according to the transrectal us with Doppler 15% or more - 1 point.

4. Decreased blood flow in adenomatous nodes according to the transrectal us with Doppler 15% or more - 1 point;

5. The density of transient zones of the prostate when detect exceeds 35 KPa - 1 point;

If the amount is not less than 4 points cease conservative therapy dutasteride and tamsulosin. If improvements of indicators does not occur, and their sum remains less than 4 points, pharmacotherapy and observation of the patient continue, and the study repeated every 3 months to achieve results.

The efficiency of the method is confirmed by the following clinical examples:

Example 1

The patient in the 62 year history No. N 00065, came in March 2011 When viewed complained of frequent difficulty urinating. Ill for 4 months. During examination: common urine analysis, complete blood count normal; questionnaire on a scale IPSS - 19 points, the index of quality of life related to urinary Qol - 5 points (bad). The Level Of P Is A - the 1.44 ng/ml; levels of total testosterone blood - 32,1 ng/ml Performed urodynamic testing, which showed a significant dysfunction of the bladder: Q max 15.7 ml/sec, Q average of 9.0 ml/sec, functional bladder volume was 243 ml Patient was performed by transrectal us prostate, according to which the volume of the prostate was 35,4 CC, the volume of hyperplastic tissue - 10,6 cub sm. According to the Doppler - flow paraurethral artery (PUA): Q max 19,0 cm/sec, Q min 6.7 cm/sec; flow pericapsular arteries (PKA): Q max 13,7 cm/sec, Q min 5.4 cm/s; the flow in adenomatous nodes of the prostate: Q max 21,4 cm/sec, Q min 6,9 cm/sec; Density adenomatous tissue in its transient area with detect amounted to 26 KPa.

The patient is administered a combination of conservative therapy: dutasteride 0.5 mg/1 time per day and tamsulosin 0.4 mg/1 time per day.

The patient re-examination after 3 months of therapy, not showing significant dynamics in the ultrasonic parameters. The rate of CT was continued. 6 months after CT held the following results are obtained.

Urination free, periodically casino. The IPSS questionnaire - 7 points, Qol=2 points (satisfactory). DOG to 1.31 ng/ml; total testosterone - 30,9 ng/ml Uroflowmetry: Q max of 18.6 ml/sec, Q average of 10.4 ml/sec, functional bladder volume 454 ml According to the transrectal us: objtemplate was 29.1 see cube (decreased 17.8%) - 1 point; the amount of hyperplastic tissue of 5.1 CC (decreased 51.9%) - 1 point; the blood flow in POIX: Q max 14,3 cm/sec (down 24.6%), Q min 4.9 cm/sec (decreased 26.9%); blood in PKA Q max 11,4 cm/sec (decreased by 16.8%), Q min 3.5 cm/sec (decreased by 35.2%) - 1 point; the blood flow in the adenomatous nodes Q max 10.6 cm/sec (decreased 51.5%), Q min 3.0 cm/sec (56.5%) - 1 point. The density of adenomatous tissue in detect amounted to 41 KPa - 1 point.

The research identified change all 5 dynamic parameters - 5 points.

Patient cancelled conservative therapy. Is dynamic observation.

Example 2

Patient P s, 49 years old, medical history, No. F, addressed to the urologist in April 2011, When viewed complained of frequent urination, weak urine stream. Ill for years. During examination: common urine analysis, complete blood count normal; questionnaire on a scale IPSS - 15 points, the index of quality of life related to urinary Qol - 5 points (bad). PSA levels - of 2.15 ng/ml; levels of total testosterone blood - 9.7 ng/ml Performed urodynamic testing: Q max 19.8 ml/sec, Q average of 8.3 ml/sec, functional bladder volume was 310 ml Patient was performed by transrectal us prostate, according to which the volume of the prostate was 52,2 cub sm., the volume of hyperplastic tissue - 27,2 cub sm. According to the Doppler - rootok in pericapsular arteries (PKA): Q max - 11.0 cm/sec, Q min - 3.2 cm/sec flow paraurethral artery (PUA): Q max - 24 cm/sec, Q min - 7,3 cm/sec; flow in adenomatous nodes of the prostate: Q max - 19,1 cm/sec, Q min - 5.2 cm/sec. The density of adenomatous tissue in its transient area with detect amounted to 33 KPa.

The patient is administered a combination of conservative therapy: dutasteride at a dose of 0,5 mg 1 time per day and tamsulosin 0.4 mg 1 time per day.

The patient performed control tests after 6 months (study 3 months showed improvement in the minimum number of indicators that led to the prolongation of CT). Urination, the patient is free, periodically casino. The IPSS questionnaire - 5 points, Qol=2 points (satisfactory). The DOG is 1.01 ng/ml; testosterone is 15.7 ng/ml Uroflowmetry: Q max to 39.4 ml/sec, Q average of 10.1 ml/sec, the functional volume of the bladder 490 ml.

According to the transrectal us: prostate volume was 40.1 CC (decreased 23.2%) - 1 point; the amount of hyperplastic tissue amounted to 14.3 CC (decreased 23.2%) - 1 point; the blood flow in PKA Q max 9.4 cm/sec (16.4%), Q min 2.2 cm/sec (decreased 31.3%); blood in POIX: Q max 17,6 cm/sec (decreased by 26.7%), Q min 2.6 cm/sec (down 64.4%) - 1 point; the blood flow in the adenomatous nodes Q max 16.9 cm/sec (decreased by 11.5%), Q min 4.8 cm/sec (down 7.7%) - 0 points; the Density of adenomatous tissue in detect amounted to 45 KPa - ball.

The research identified change 4 dynamic parameters - 4 points.

Patient cancelled conservative therapy. Is dynamic observation.

Example 3

The patient is In s, 67 years old, medical history, No. V, addressed to the urologist in October 2011, When viewed complained of frequent, occasionally difficulty in urination, weak urine stream. Ill for 10 months. During examination: common urine analysis, complete blood count normal; questionnaire on a scale IPSS - 17 points, Qol was 5 points (bad). PSA levels - 2.7 ng/ml; levels of total testosterone blood - to 15.2 ng/ml Performed urodynamic testing, which showed a significant dysfunction of the bladder: Q max 13.7 ml/sec, Q average of 4.9 ml/sec, functional bladder volume was 118 ml Patient was performed by transrectal us prostate, according to which the volume of the prostate was 61.4 CC, the volume of hyperplastic tissue - 41 cub sm. According to the Doppler - flow paraurethral artery (PUA): Q max - 21.3 cm/sec, Q min - 6.5 cm/s; the flow in pericapsular arteries (PKA): Q max - 13.5 cm/sec, Q min - 4.3 cm/s; the flow in adenomatous nodes of the prostate: Q max - 11.2 cm/sec, Q min - 4.1 cm/sec. The density of adenomatous tissue in its transient area with detect amounted to 21 KPa.

The patient is administered a combination of conservative therapy: dutasteride 05 mg/1 time per day and tamsulosin 0.4 mg/1 time per day.

Performed after 3 months control study showed no significant improvement on any of the parameters. The rate of CT was continued. Another study was conducted after 6 months of combination therapy.

Urination, the patient was free, periodically casino. The IPSS questionnaire - 7 points, Qol=2 points (satisfactory). DOG - 1.6 ng/ml; testosterone - 17.2 ng/ml Uroflowmetry: Q max is 20.1 ml/sec, Q the mean of 7.9 ml/s, the functional volume of the bladder 213 ml. According to the transrectal us: prostate volume was 49.7 CC (decreased by 19%) - 1 point; the amount of hyperplastic tissue - 29,3 CC (decreased by 28.5%) - 1 point; the blood flow in POIX: Q max - 19,1 cm/sec (decreased by 10.4%), Q min - 3,7 cm/sec (decreased by 43%); blood in PKA Q max - 13.5 cm/sec (reduced to 0%), Q min 3.8 cm/sec (down 11.5%) - 0 points; the blood flow in the adenomatous nodes Q max - 10.2 cm/sec (down 9%),Q min - 3.8 cm/sec (down 7.3%) - 0 points. The density of adenomatous tissue in detect amounted to 27 KPa - 0 points.

The research identified the changing dynamic parameters - 2 points.

The patient continued conservative therapy dutasterida in the dosage of 0.5 mg 1 time per day and tamsulosin dosage of 0.4 mg 1 time per day. Control tests are planned in 3 months.

The presented work is based on the analysis of the treatment of 112 patients with BPH, which wire is stayed conservative in CT 2011 Road urological center NPH CST JSC "RZD" on strocov-Chief. The average age of the men included in the study, was 59,0 and 1.4 years.

Prior to, and during the control visit as part of a comprehensive survey was performed transrectal ultrasound (transrectal us) mud in gray-scale mode, and Doppler assessment of blood flow in the mud system capsular (PKA) and paraurethral arteries (POIX).

To obtain quantitative characteristics of arterial blood flow was used to calculate maximum (Q max) and minimum (Q min) systolic velocity and wholesaleing of the resistance index (RI), characterizing vascular resistance. All studies were performed on the ultrasound system Zonare-Ultra abdominal sensor F 9-4 MHz.

All the obtained data were statistically processed with the calculation of descriptive statistical parameters: arithmetic mean values (M) and standard deviation (σ). To establish evidence of differences (p) between the data used T-test for paired samples.

Assessment of the effectiveness of CT with a control survey was conducted every 3 months of therapy.

The treatment allowed us to identify a group of patients (n=14), which pharmacotherapy of BPH was discontinued after six months of therapy. In the data the nd group was determined by marked regression of clinical symptoms, the volume reduction of hyperplastic tissue mud to a minimum size, reduced blood flow parameters in the mud.

Prostate volume in patients significantly decreased after 3 months of treatment and continued to decline to a six-month observation. Volume hyperplasia decreased by 58% and to 6 months remained the same. The blood flow in pericapsular and paraurethral arteries has changed in the direction of reducing the maximum and minimum speed to 6 musicmedicine (table 1).

Table 1
Dynamics of indicators of transrectal us in patients on background CT
The duration of therapy0 months3 months6 monthsp 0-3p 0-6
V prostate41,7±2,335,7±1,031,6±2,10,020,02
V hyperplasia10,2±1,14,0±1,13,0±1,10,0040,004
Vmax PKA15,9±09 14,4±1,313,0±0,40,250,0005
Vmin PKA4,5±0,4the 3.65±0,33,1±0,030,010,05
Vmax POIX17,4±1,316,6±1,613,3±0,30,90,05
Vmin POIX5,2±0,45,5±0,74,1±0,30,40,008

Thus, the obtained data testify to the positive dynamics of changes in the size of the prostate hyperplasia, blood flow in the capsular (PKA) and paraurethral arteries (PUA), blood flow in adenomatous nodes and the effectiveness of the course of dutasteride and tamsulosin have a specific group of patients with BPH.

The combination of these factors results in remission of the disease, allowing you to undo conservative therapy.

Compared with the known, this method has several advantages:

- allows you to objectively determine the duration of treatment of the patient;

- allows you to exercise effective control of the ü the effectiveness of the treatment.

- allows to significantly reduce the cost of treatment of this disease;

- helps reduce medication burden on the patient's body.

The inventive method of treatment of benign prostatic hyperplasia has been tested on a significant volume of clinical material, showed good results and can be recommended for use in urological practice.

1. A method of treating benign prostatic hyperplasia, which consists in performing a dynamic examination of the prostate and the appointment of pharmaceutical preparations, characterized in that the dynamic survey carried out by the methods of transrectal ultrasound transrectal us) with Doppler and detect (SAG) prostate cancer to drug therapy and after 3, 6 and 9 months thereafter, conduct a comparison of the values of the size of the prostate size, prostate hyperplasia, blood flow in the capsular and paraurethral arteries, blood flow in adenomatous nodes and density of transient zones of the prostate at SAG and if the values of the investigated parameters according to the transrectal us decrease by 15% or more for each the indicator is scored 1 point, if the density of transient zones of the prostate when detect exceeds 35 KPa - 1 point, if the amount is not less than 4 points cease conservative terap the Yu, if a score of less than 4, continue therapy and research, follow through the next 3 months.

2. The method according to claim 1, characterized in that the conservative medicamental treatment is carried dutasterida in the dosage of 0.5 mg 1 time per day and tamsulosin dosage of 0.4 mg 1 time per day.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: what is presented is using at least one protease for producing a drug preparation for treating and/or preventing benign prostatic hypertrophy/hyperplasia wherein the drug preparation is acceptable for the oral administration with at least one protease being specified in a group consisting of plant and microorganism proteases, and with at least one protease being administered in the amount of 1 to 100 mg/kg of body weight, and a respective pharmaceutical preparation.

EFFECT: what is shown is reducing high vascular endothelial growth factor in patient's blood under the action of a mixture of enzymes that makes it possible to inhibit angiogenic growth factors (VEGF), thereby leading to lower vascularisation, and reducing benign prostatic hypertrophy/hyperplasia, with the enzymatic therapy under the present invention having no effect on the normal VEGF level.

13 cl, 7 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely urology, and may be used for treating suppurative septic complications of prostate adenoma. For this purpose, with underlying administering antibiotics, ozonised saline solution in the concentration of 3 to 6 mg/l in the amount of 200 to 400 ml is additionally intravenously administered; the therapeutic course is 3-5 injections depending on the patient's state. Besides, ozonised saline solution in the concentration of 5 to 8 mg/l is injected into the bladder in the preoperative preparation period, and from the second postoperative day, saline solution is introduced drop-by-drop in the amount of 400.0 ml daily five times with a two-way flushing system.

EFFECT: method enables reducing the risk of urosepsis, eliminating intoxication and accelerating postoperative wound healing of a BPH bed by anti-inflammatory, detoxification, analgesic action, improved blood rheology and microcirculation, increased local immunity with activated regenerative and reparative processes.

2 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (1), in which Ar is a group of formula (Ar-1) or (Ar-2), in which R1 is a halogen, R2 is hydrogen, R3 is hydrogen, R4 is hydrogen, alkyl or alkenyl, X is a nitrogen atom or CH, R5 and R6 are each hydrogen and h equals 1; 1 equals 1 or 2; m equals 1 or 2; n equals 0, 1 or 2; o equals an integer from 0 to 3, under the condition that n and o are equal to 0 at the same time. Values of group A are as given in claim 1 of the invention. Described also is a pharmaceutical composition having agonistic activity with respect to 7 serotonin (5-HT4-receptors), which contains a compound of formula (1) and an agent which stimulates enterokinesis or improves functioning of the alimentary canal, which contains a compound of formula (1) as an active ingredient.

EFFECT: novel compounds are obtained and described, which have strong affinity towards 4 serotonin receptors, which are useful as an agent which stimulates enterokinesis or an agent which improves functioning of the alimentary canal.

28 cl, 233 ex, 29 tbl

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to urology, and can be used for treatment of chronic abacterial prostatitis in men, which is not connected with dysfunction of urethral sphincter. For this purpose, efficient amount of fispemiphene is introduced to patient who needs it. Introduction of fispemiphene is performed in amount in the range from 0.1 to approximately 100 mg/kg of body weight.

EFFECT: invention ensures efficient treatment of abacterial prostatitis at the early stage of disease where only histological changes of prostate gland are present without presence of urethral sphincter dysfunction, with drug fispemiphene, which demonstrates antagonistic activity to estrogen receptors in particular with respect to prostate tissue.

2 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to field of pharmaceutical industry, in particular to composition, which contains epigallocatechine-3-gallate as active component and target additive. Pharmaceutical composition for peroral introduction, which contains epigallocatechine-3-gallate and block-copolymer of oxyethylene and oxypropylene, in which content of hydrophobic block constitutes not less than 50 wt %, and molecular weight of hydrophilic block constitutes 2250 Dalton and not more, with specified weight ratio of epigallocatechine-3-gallate and block copolymer 1:1-10:1. Application of upper described pharmaceutical composition for treatment of atopic dermatitis, Crohn's disease, adenomyosis, and hyperplastic diseases of prostate.

EFFECT: composition has increased bioavailability in peroral application, improves absorption of active compound epigallocatechine-3-gallate in blood flow.

6 cl, 2 dwg, 4 tbl, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmacy, namely technology of preparation of rectal suppositories. The suppositories with solid licorice extract consist of solid licorice extract 0.75 g on a hydrophilic base, polyethylene glycol 6000 1.25 g and polyethylene glycol polystear 0.25 g.

EFFECT: making the preparations exhibiting anti-inflammatory action, and also a positive effect on the hormonal status and the copulative function.

7 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel acid-additive salts of pyrrolopyrimidinone derivative, represented by formula (1) which is selected from gentisate, maleate, citrate, fumarate and semitartrate salts, which possess improved properties in their application, in particular higher stability.

EFFECT: invention also relates to method of obtaining acid-additive salts of pyrrolopyrimidinone derivative, represented by formula (1) and to pharmaceutical composition, containing them, for treatment and prevention of erectile dysfunction, pulmonary arterial hypertension, chronic obstructive lung disease, benign prostate gland hypertrophy and diseases of lower urinary tract.

11 cl, 30 ex, 7 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: declared group of inventions relates to medicine. There are declared methods of treatment and preventive treatment of prostate cancer in males and a method for treatment of prostate cancer in male dogs involving a single agent therapy in the form of introducing a therapeutic amount of N,N'-bis(2,3-butadienyl)-1,4-butane-diamine or its pharmaceutically acceptable salt or solvate. The therapeutic amount is specified within the range from 1-100 mg/kgbody weight and dosed within the range from twice a week to once a day.

EFFECT: group of inventions has high therapeutic efficacy.

26 dwg, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to coated pharmaceutical formulations with a controlled-release active substance and to the use thereof for treating benign prostatic hyperplasia. The formulation contains a therapeutically effective amount of the active substance representing tamsulosin or its pharmaceutically acceptable salt encapsulated in a granulated core, and an insoluble permeable polymer found both in the granulated core and in the coating. Said pharmaceutical formulations may also contain a surfactant and other optional excipients. Besides, the invention refers to a method for preparing the pharmaceutical formulations which involves mixing core ingredients, granulating, pressing and shaping in a sphere, drying and coating.

EFFECT: invention provides the formulations with pH-independent release of the active substance, low inter-individual variability and low biological variability.

14 cl, 7 ex

FIELD: medicine.

SUBSTANCE: The invention relates to pharmacology, in particular, to medication for preventing or treating herpes labialis or herpes genitalis. The homeopathic medication or biologically active additive with anti-viral effect or preventing or treating herpes labialis or herpes genitalis contains: Nisylen, Cepa, Euphrasia, Belladonna and Mericulis Solubilis, furthermore, the components are present with a certain dilution and amount. The combination of the said components is used for production of homeopathic medication or biologically active additive with anti-viral effect or preventing or treating herpes labialis or herpes genitalis.

EFFECT: production of medication which effectively treats herpes labialis or herpes genitalis.

14 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: group of inventions relates to a crystalline minocycline base and specifically to three crystalline forms denoted form 1, form II and form III and methods for production thereof (form I, II and III).

EFFECT: obtaining novel, more stable forms of a minocycline base.

14 cl, 6 ex, 8 dwg

FIELD: medicine.

SUBSTANCE: invention relates to method of obtaining beta-lactam antibiotics in for of polymer complex gels with silver ions, which includes preparation of solutions of sodium salts of antibiotics of 0.1-1.0 mol/l concentration, solution of silver nitrate of 0.1-1.0 mol/l concentration, mixing observing ratio antibiotic:silver not less than 1 and not higher than 9, obtained solutions at temperature 10÷40°C with formation of dispersion of white colour, keeping dispersion without mixing until its decolouration with formation of colourless transparent gels, characterised by the fact that as antibiotic used are oxacillin derivatives, solutions of sodium salts of antibiotic contain 50-90 volume percent of water and 10-50 volume percent of organic solvent.

EFFECT: gel is thermally stable, ensures higher bactericidal and antibacterial activity and is prepared without additional polymer thickening agents.

11 dwg, 4 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to field of pharmaceutics and medicine and deals with pharmaceutical composition in form of water solution for injections, containing 4-iodine-3-nitrobenzamide, physiologically compatible buffer and cyclodextrin, application of said composition for treatment of viral disease and cancer and method of treating viral disease and cancer.

EFFECT: composition possesses increased solubility in water solutions.

55 cl, 12 dwg, 10 tbl, 10 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine, particularly to oncology, and concerns treating breast cancer which is negative in relation to an estrogen receptor (ER), a progesterone receptor (PR) and a human epidermal growth factor 2 (HER2). That is ensured by presenting the method or the use of the combination of an effective amount of 4-iodine-3-nitrobenzamide or its pharmaceutically acceptable salt in a combination with gemcitabine and carboplatin.

EFFECT: invention provides the effective treatment of the mentioned type of breast cancer.

25 cl, 6 dwg, 8 tbl, 9 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, and aims at anaesthetic care of post-burn oesophageal bougienage. Before a bougienage procedure, a solution 25-30 ml containing sterile glycerol and 2% lidocaine hydrochloride in the following proportions: sterile glycerol - 100 ml, 2% lidocaine hydrochloride - 10-15 ml is intaken. Besides, reinforced pharyngeal reflex requires cerucal 2 ml to be intramuscularly injected 20-30 min before the bougienage procedure.

EFFECT: method enables pain relief during the post-burn bougienage procedure and prevented mucosal injures.

2 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to oncology, and can be used for treatment of cerebrovascular diseases and asthenic syndrome. For this purpose mixture of medications, consisting of cytoflavin 2.0 ml and novocaine 0.5% - 5.0 ml, is introduced in lymphotropic way by interstitial injection into posterior zone of neck suboccipitally.

EFFECT: invention makes it possible to achieve reduction of dose of used medications, as well as minimise development of undesirable reactions of introduced medications.

3 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely occupational pathology, and may be used for correction of cognitive dysfunction and vegetative-sensory polyneuropathy in the patients with vibration disease. That is ensured by prescribing health resort treatment and drug-induced therapy. The drug-induced therapy involves the intravenous drop-by-drop introduction of cytoflavin 20 ml per 5% glucose 200 ml daily for 10 days.

EFFECT: invention provides improving higher cortical functions in the given category of the patients due to the developed enhanced regimen of the preparation dosage.

1 dwg, 1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I), having histone deacetylase (HDAC) enzyme inhibiting action, stereoisomers, hydrates, solvates and pharmaceutically acceptable salts thereof, compounds of formula (II), compounds selected from a list, a method of producing compounds of formula (I), a pharmaceutical composition, an inhibition method and methods of treating using compounds of formula (I). In formulae

and

R denotes substituted or unsubstituted groups selected from (C6-C10)aryl, (C3-C12)cycloalkyl, heteroaryl, (C6-C10)aryl (C1-C6)alkyl and heterocyclyl; where the heterocyclyl hereinafter is a 5-10-member ring radical which consists of carbon atoms and 1-5 heteroatoms selected from nitrogen, oxygen and sulphur, and heteroaryl hereinafter is an aromatic heterocyclyl, and each aryl, cycloalkyl, heteroaryl, arylalkyl and heterocyclyl can be substituted with one or more substitutes selected from halogens, including fluorine, chlorine, bromine, iodine, (C1-C6)alkyl, (C1-C6)alkoxy, (C6-C10)aryl, halogen(C1-C6)alkyl, (C6-C10)aryl(C1-C6)alkoxy, -O-(C3-C12)cycloalkyl, -O-CH2-(C3-C12)cycloalkyl, hydroxyl, NRaRb and ORa, where Ra and Rb independently denote (C1-C6)alkyl and aryl; R1 denotes (C6-C10)aryl; R2 and R3 independently denote hydrogen, (C1-C6)alkyl, -COOR5, -CONR5R6, -CH2NR5R6, -CH2CH2NR5R6, -CH2CH2OH or -CH2OH; provided that one of R5 or R6 is hydrogen or unsubstituted alkyl, the other is neither hydrogen nor unsubstituted alkyl; R5 and R6 independently denote hydrogen, (C1-C6)alkyl, (C3-C12)cycloalkyl, (C6-C10)aryl, (C6-C10)aryl(C1-C6)alkyl, heteroaryl or heteroaryl(C1-C6)alkyl, which can be unsubstituted or substituted; or R5 and R6 can be combined to form a saturated or unsaturated 3-8-member ring having 0-2 heteroatoms, including N, O or S; where the heteroaryl hereinafter is a 5-10-member ring radical consisting of carbon atoms and 1-5 heteroatoms selected from nitrogen, oxygen and sulphur, and each alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl can be substituted with one or more substitutes selected from halogen, including chlorine, fluorine, bromine or iodine,(C1-C6)alkoxy and NRaRb; R4 denotes OH, (C6-C10)aryl, ortho-substituted aniline or amino (C6-C10) aryl, which can be optionally substituted with one or more groups selected from halogens, including fluorine, chlorine, bromine, iodine, hydroxyl, amino groups or (C6-C10)aryl; X denotes -NR7-, -CONR7- or -N R7CO; R7 denotes hydrogen or (C1-C6)alkyl; Y denotes (C6-C10)aryl or (C6-C10)aryl(C2-C6)alkenyl; m is an integer from 0 to 1; n is an integer from 0 to 1; o is an integer from 0 to 7; and p is an integer from 0 to 1.

EFFECT: improved method.

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions relates to medicine. A method of treating a disease, a disorder or a condition caused by a non-homologous DNA end-joining defect involves the introduction to an individual of a therapeutically effective amount of an agent which inhibits RAD51 activity, interrupts RAD51 focus formation or interrupts the assembly of a functional reparation complex of the homologous DNA recombination; and the therapeutically effective amount of treatment providing cell DNA damage. The declared pharmaceutical composition contains a first coating for first release of the therapeutically effective amount of the agent which inhibits RAD51 activity, interrupts RAD51 focus formation, interrupts the assembly of the functional reparation complex of the homologous DNA recombination; and a second coating for second release of a DNA damaging agent. Said agent represents 3-((dimethylamino)methyl)-K-(2-(4-(hydroxycamoyl)phenoxy)ethyl)benzofuran-2-carboxamide.

EFFECT: group of inventions is effective in treating the diseases caused by the non-homologous DNA end-joining defect, RAD51 expression, particularly in treating cancer.

12 dwg, 1 tbl, 18 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula I

and/or to all isomer forms of a compound of formula I and/or to mixtures of these forms in any proportions, and/or to physiologically acceptable salts of the compound of formula I, wherein R1 represents 1) -(C6-C14)-aryl-Z, wherein Z represents aminomethylene, 2) Het-Z, wherein Z represents amino group, and wherein Het is unsubstituted or additionally monosubstituted by group T, R2 represents 1) -(C0)-alkylene-(C6-C14)aryl, wherein aryl is unsubstituted or mono- or disubstituted by group T or 2) -(C0)-alkylene-Het, wherein Het is unsubstituted or monosubstituted by group T, R3 represents 1) -(C0)-alkylene-(C6-C14)-aryl, wherein aryl is unsubstituted or mono- or disubstituted by group T, 2) -O-(C6-C14)-alkylene(C6-C14)-aryl, wherein aryl is unsubstituted or monosubstituted by group T, 3) -(C0)-alkylene-Het, wherein Het is unsubstituted or mono-, di- or trisubstituted by group T, 4) -(C0)-alkylene-(C6-C14)-aryl-Q-(C6-C14)-aryl, wherein both aryl radicals are unsubstituted, 5) -(C0)-alkylene-(C6-C14)-aryl-Q)-Het, wherein aryl and Het in each case are independently unsubstituted or disubstituted by group T, 6) -(C0)-alkylene-Het-Q-Het, wherein both radicals Het are unsubstituted, Q represents a covalent bond, -(C1-C4)-alkylene, -N((C1-C4)-alkyl)- or -O-, T represents 1) halogen, 2) -(C1-C6)-alkyl, wherein alkyl is unsubstituted disubstituted by group -(C1-C3)-fluoralkyl or -N-C(O)-(C1-C4)-alkyl, 3) -(C1-C3)-fluoralkyl, 4) -(C3-C8)-cycloalkyl, 5) -O-(C1-C4)-alkyl, 6) -O-(C1-C3)-fluoralkyl, 7) -N(R10)(R11), wherein R(10) and R(11) independently represent hydrogen atom or -(C1-C6)-alkyl, 8) -C(O)-NH-R10, 9) -SO2-(C1-C4)-alkyl, 10) -SO2-(C1-C3)-fluoralkyl, R4 and R5 are identical and represent hydrogen atom, and R6 represent hydrogen atom with said Het being 5-10-member ring system consisting of 1 or 2 coupled ring systems, and wherein one or two identical or different heteroatoms are selected from oxygen, nitrogen and sulphur. Also, the invention refers to the use of the compound of formula I for preparing a drug.

EFFECT: there are prepared new compounds exhibiting antithrombotic activity, which particularly inhibit blood coagulation factor lXa.

6 cl, 2 tbl, 9 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine and pharmacy and can be applied in production and application of solutions for intravenous introduction in treatment of conditions, associated with endogenous intoxication. Disintoxication solution contains components in the following ratio (wt %): sodium hypochlorite 0.04-0.08, sodium chloride 0.50-1.00, aminoethane sulfonic acid 0.02-1.20.

EFFECT: novel infusion solution is claimed.

4 ex, 1 tbl

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