Pharmaceutical composition for treating diseases of lower part of genitourinary system

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to pharmacology and medicine and represents pharmaceutical composition for treating diseases of lower part of genitourinary system in form of suppositories, which includes bioactive compound and fat basis, characterised by the fact that as bioactive compound, composition contains mixture of amino acids: glutamic acid, lysine, alanine, arginine and glycine, and additionally zinc in form of zinc chloride, components in composition being in specified ratio per one suppository with weight 2.7-2.9 g.

EFFECT: extension of spectrum of medication action.

3 cl, 6 ex, 1 tbl

The invention relates to medicine, in particular to medicine, namely to suppositories containing agent for the treatment of diseases of the lower section of the genitourinary system. It can be used in General medical practice in the treatment of urological and gynecological diseases.

It is known for the treatment of chronic prostatitis in the form of suppositories comprising one suppository mass of 2.0-2.2 g 4-6 mg of bioactive compounds concentrate of the extract of the prostate gland of cattle and additionally concentrate liquid purified α-interferon or interferon [RU No. 2160114, MCL⁶AC 35/48, 2000]. Suppositories made on the basis of gelatin, glycerin and sodium carbonate-bicarbonate buffer. The presence of interferon, giving antiviral protection, allows the use of suppositories for RU # 2160114 in the treatment of chronic prostatitis taking place on the background of immunodeficiency.

However, the effectiveness of these suppositories low, which is connected, apparently, with low concentrations of bioactive compounds and instability of interferon in this composition.

Most similar in essential characteristics of the claimed composition is a pharmaceutical composition in the form of suppositories containing suppository the weight of 2.15 to 2.35 g of 0.05-0.40 g of bioactive compounds and 0.7 g of antimicrobial drugs [RU No. 2304979, Ml⁷C 38/02, 2007]. As bioactive compounds, the composition comprises a complex of bioregulatory peptides of the prostate gland of cattle. As an antimicrobial agent composition includes antibiotics of the fluoroquinolone, or penicillins, or cephalosporins, or tetracyclines and other Suppositories for RU # 2304979 could include antiviral and Antiprotozoal drugs. They were tested on the model of prostatitis in white rats-males.

The presence of antibiotics in suppositories for RU # 2304979 can cause a person to the usual complications associated with allergic reactions to antibiotics, as well as reduced levels of immunity, usually caused by antibiotics.

However, the pharmaceutical compositions according to EN No. 2160114 and RU # 2304979 share a common drawback - use as bioactive compounds complex bioregulatory peptides of the prostate gland of cattle.

Like any tool, derived from natural raw materials, they have not fully identified the structure as methods for determining its complicated, and methods of standardization, and are not always available and producer, and researcher. The content of active substances does not exceed 20%; the drug is released from natural raw materials, always contains a number of high-molecular compounds, netdelay what's the active component.

All this narrows the range of action of a drug.

The technical result, which is aimed by the invention, is to expand the range of action of a drug.

This technical result is achieved in that the pharmaceutical composition in the form of suppositories comprising the bioactive compound and the fat basis, as bioactive compounds contains a mixture of amino acids, including glutamic acid, lysine, alanine, arginine and glycine, in addition to the zinc in the form of zinc chloride in the following ratio of components in the composition in grams per one suppository mass of 2.7-2.9 g:

The pharmaceutical composition may further comprise 10-30 µg of selenium in the Orme of sodium Selenite anhydrous or at 0.020-0.035 g of sodium femoropatellar one suppository.

It is known that certain amino acids regulate various physiological functions of living organisms [Chirkin A.A., Danchenko EO Biochemistry. M., "Medical literature", 2010, 608 S.]. So, it is known tool in the form of suppositories for the treatment of female sexual dysfunction [RU application No. 2000120537, MCL⁷AC 45/06, 2002], including 2-10 mg antagonist α-adrenergic receptors (yohimbine, phentolamine, and others) and 1-8 g arginine, showing NO donor activity.

Also known pharmaceutical antiherpetic composition in the form of, for example, suppositories [RU No. 2264819, MCL⁷AC 35/74, 2005 and RU application No. 2004128635, MCL⁷AC 31/19, 2006], including virginny vaccine Antiherpes virus effect of the drug, as well as immunomodulator polyoxidonium and additionally valine, lysine, isoleucine, and a combination of at least two amino acids selected from the group including, in particular, alanine and arginine.

Also known pharmaceutical composition in the form of suppositories for the treatment of erectile dysfunction [EN application 2000100301, MCL⁷AC 31/475, 2001], including 2-8 mg yohimbine and 1-4 g of arginine.

None of the known pharmaceutical compositions comprising individual amino acids, or even a mixture of amino acids [RU NO. 2264819, RU application No. 2004128635], do not show activity in the treatment of diseases of the prostate. All systems shall be controlled compositions include funds from other classes, taken as basic, and amino acids included in them separately, and usually in large numbers.

It is known that when combined in a composition separate biologically active substances it is impossible to foresee whether it will be a summation of their efficiency, and even whether the components are compatible [see, for example, Societyhow the NI Blood substitutes blood loss and shock. L., "Medicine", 1984, p.148; Ed. by Oleinik S.A. Sports pharmacology and dietetics. M.: OOO "Idiles", 2008, 256 S., Principles of clinical nutrition. The materials of the lectures for the courses of the European Association for parenteral and enteral nutrition. M., "Intelteck", 2003, 416 S.].

Therefore manifested the claimed composition physiological activity in the treatment of diseases of the prostate gland (prostatitis, adenoma of the prostate gland) and, in addition, gynecological diseases such as vaginitis, was the unexpected and unpredictable in advance.

All components of the claimed composition are produced by the industry. Were used glutamic acid company Ajinomoto, Japan, lysine company Sigma-Aldrich, Germany, alanine company Merk, Germany, arginine company Ajinomoto, Japan, glycine company Sijo city Huayang chemical, China and zinc chloride (Merck, Germany), and its content in the claims given in the calculation of the zinc.

When the song includes 10-30 micrograms of selenium, he was taken in anhydrous form of sodium Selenite.

The composition may also include at 0.020-0.03 to 5 g of sodium femoropatellar. As the basis can be used, for example, cocoa butter, edible oils, a mixture of mono-, di - and triglycerides of fatty acids (Witepsol) and other fatty bases allowed Pharmacopoeia.

Suppositories prepared as follows.

Example 1. Manufacturing technology suppositories

1. Getting suppozitornoj mass.

1.1. Getting premix.

The premix is prepared in a homogenizer with a heated jacket.

For the preparation of the premix in the homogenizer put enough suppozitornoj bases (Witepsol /Witepsol/ W35) and melted.

Then place a pre-weighed ingredients: glutamic acid, alanine, lysine, arginine, glycine, zinc, perhaps, sodium panaromaticky and selenium. Homogenization premix hold for 20-30 minutes. At the end of the process check the quality of the premix weight should be uniform.

1.2. Mixing the premix with the basis

Suppozitornyj basis (Witepsol /Witepsol/ W35) are placed in a reactor and melted. Then add to the base premix and stirred for 1 hour. Suppozitornaja the weight should be homogeneous with no visible inclusions.

2. Molding suppositories

2.1. Filling blisters suppozitornyj mass (PASOK is).

The packaging of the drug in blister packaging carried out on a dosing machine. Suppozitornyj mass is passed into the hopper of the batching machine. Packing suppozitornoj mass in the cell is held at a constant temperature and stirring.

Blister packaging, filled suppozitornyj mass, by means of the guide rollers wound into rolls and transmit the operation of the Cooling suppositories".

2.2. Cooling suppositories

Cooling suppositories is carried out in a refrigerated Cabinet at a temperature of 10-15°C for 1-2 hours.

Was investigated acute and chronic toxicity of the proposed suppositories in accordance with the requirements of the "Manual on experimental (preclinical) study of new pharmacological substances (2005)". The study of the acute toxicity was carried out on 36 outbred mice-females; study of chronic toxicity were performed on 45 outbred mice-females and 9 rabbits male.

In the study of acute toxicity of the drug was carried out in ascending doses of 1.0, 2,0, 4,0, 8.0 and 10.0 g/kg (finished dosage form) according to the Litchfield-Wilcoxon signed on the basis of the average weight of suppositories - 2,0,

Found that a single injection of study drug to animals in doses exceeding therapeutic recommended for klinicheskoj the application, more than 500 times, does not cause toxic reactions, which testifies to the great therapeutic breadth of the drug.

The study of the chronic toxicity of the drug indicates the absence of side effects with the use of suppositories for 30 days at doses exceeding therapeutic more than 200 times. In the study no significant effect of study drug on morphological, biochemical parameters in peripheral blood and erythrocyte sedimentation rate, and the resistance of erythrocytes. Along with that content was determined in the serum total protein by the method of Lowry, potassium and sodium by plasma spectrophotometry. After completion of the experiment conducted pathomorphological study of the brain and spinal cord, spinal ganglia, thyroid gland, parathyroid glands, adrenal glands, testes, pituitary gland, heart, lung, aorta, liver, kidney, bladder, pancreas, stomach, small intestine, colon, thymus, spleen, lymph nodes, bone marrow.

When assessing the General condition of the animals, morphological and biochemical indices of peripheral blood, the morphological status of the internal organs, the state of the cardiovascular and respiratory systems, liver and kidney pathological changes in the organism not found

No General toxic effect of the suppositories can be recommended for testing in vivo in experimental urogenital pathology. It was studied the pharmacological effect of the claimed composition in experimental models of prostate and vaginitis.

Example 2. The effectiveness of suppositories in the rat model irritative prostatitis

The experiments were carried out on outbred rats male weighing 180-200 g, were grown in the nursery RAMS "Rapolano". Before the experiments, animals were subjected to 14-day quarantine and randomization. Labels and individual numbers of animals recorded in the protocols of laboratory tests. Animals were kept in vivarium conditions on a standard diet.

All experimental animals were simulated chronic prostatitis through the introduction of a 10%aqueous solution of Dimexidum in water, mixed with turpentine in a volume ratio of 4:1. Before the introduction of the mixture was shaken for 1 min before the formation of a fine emulsion. Received freshly prepared emulsion was injected to rats rectal to a depth of 20-25 mm in a volume of 1 ml using a device for rectal infusion (dispenser), preventing the morbidity of the procedure, while the animals were fixed in a horizontal position by hand in canvas glove. The mixture before you put the eat which was to obtain a fine emulsion.

In the specified rectal injection of a mixture of turpentine is used to create pathological congestion in the prostate gland, and an aqueous solution of Dimexidum is a conductor that improves interstitial penetration of turpentine, and analgesic effect.

The test drugs were administered to rats of different groups individually in the following doses over 28 days from the date of simulation pathology. Animals were divided into following groups of 10 rats each:

- intact animals;

control 1 (irritative prostatitis);

control 2 (irritative prostatitis+drug comparison - Prostatilen (bioregulatory peptides of the prostate gland of cattle), 190 mg/kg RG);

- irritative prostatitis+declare suppositories, 240 mg/kg R.G. Study drugs were injected every male individually in molten form using atraumatic tip.

Determined the reduction of urodynamics (in terms of spontaneous daily diuresis), using individual metabolic cages firm "Techniplast, Italy). Defined background values of diuresis (28 days from the date of simulation pathology) and values at the end of therapy (58-59 days).

Daily urine to determine the level of secreted protein by quantitative method turbidimetry.

After collecting the urine in exchange CL is located rats were subjected to instant decapitate under light ftorotanovom anesthesia. Blood sampling was carried out in vacuum tubes with a coagulation activator "Vacutest SER" company "Vacutestkrma" (Italy). The samples were let warm up for 30 min at 37°C in an incubator, cooled for 1 h in the cooling chamber was centrifuged at 2050 rpm, the Serum was separated in tubes Eppendorf Microtubes firm "Plastibrand" (Germany).

In the serum was determined by testosterone levels (enzyme-linked immunosorbent assay, a set of firm "HEMA"), nitrogen oxide (method photometry Griss at 520 nm), thiobarbituric-reactive products - malondialdehyde (by means of photometry at 537 nm), C-reactive protein (enzyme-linked immunosorbent assay, a set of firm "BD"), ceruloplasmin (by means of photometry Revin), the activity of prostatic acid phosphatase (kinetic method photometry, set firm "olivex Diagnosticum").

For histological study ventral part of the prostate gland were fixed in 10% neutral formalin and after the standard wiring through a series of solvents were placed in paraffin. The tissue sections with a thickness of 5-7 µm were stained with haematoxylin-eosin.

To compare the severity of prostatitis in different groups have developed the following 5-point scale:

1 point - signs of prostatitis (small foci of fibrosis, interstitial, lymphocytic and histiocytomas infiltration);

2 points - foci of chronic prostatitis vospalitelnoe infiltration (mainly interstitial), occupying less than 1/4 slice gland;

3 points - the foci of prostate with large inflammatory infiltrates around ducts, acini, and blood vessels, with accumulation of cells in the Lumina of the glands, occupying 1/4-1/2 slice gland;

4 points - expressed prostatitis, spectacular 1/2-3/4 slice gland;

5 points - pronounced prostatitis defeat more than 3/4 of a slice of cancer. Statistical processing of data was performed using the standard software package "Microsoft Excel". The significance of changes was calculated using t-student test.

Simulation of the experimental prostatitis is accompanied by the development of significant pathological changes of urodynamics in rats after 28 days from the moment of introduction of logogen (mixture of turpentine with Dimexidum). The introduction of a mixture of turpentine with Dimexidum has led to the development of prostatitis, which was accompanied at the expense of the inflammatory increase in mass-volume indicators gland, reduction of urodynamics. In all experimental groups, daily diuresis after 28 days of simulation (background pathology) was reduced by more than 40%. Proteinuria was significantly increased (5.4 times), which is explained by the release of inflammatory exudate in the lumen of the urethra in males and hit its components in urine. Against the background of a pathology has increased release of tissue isoenzyme of acid phosphatase is basically what about the token prostatitis and adenoma. Also noted increased levels of acute-phase protein ceruloplasmin (24 times) and C-reactive protein (2.2 times) and decreased testosterone levels.

Experimental model of prostate leads to an inflammatory increase in mass-volumetric size of the ventral prostate during the assessment of the effects of drugs on the course of prostatitis was evaluated by the value of the mass of the gland of rats at the end of the experiment.

Increased cancer was mainly due to the swelling and hyperemia of the gland tissue. These changes play a significant role in the deterioration of urodynamics in the passages of the urine and are a major factor in the development of hyperlactatemia wall of the bladder in patients with prostatitis and BPH, as well as a cause of dysuric disorders, including pain during urination.

Therapy study medication for 1 month resulted in a significant normalization of the mass of the prostate gland of male rats with experimental prostatitis. Prostatilen reduced the weight of the ventral prostate by 23.7% compared to the control without treatment. Studied suppositories slightly more contributed to the normalization of this index is reduced by 30.4%.

Amid drug comparison Prostatilen was a significant reduction of proteinuria in rats 3.2 times and restore the s diuresis by 54.3% compared with the background pathology.

Introduction the study of suppositories helped restore urodynamics (increase diuresis 22,4%), and reduction of daily excretion of protein in urine (proteinuria) - 2,2 times in comparison with the background pathology in this group.

Therapy drug compare Prostatilen contributed to the decrease in the intensity of oxidative processes in the gland, which was expressed by a significant decrease in the level of nitric oxide (1.5 times), and products of reacting with thiobarbituric acid (TBA-RP) (2.2 times) compared to control animals without treatment.

The introduction of rats studied suppositories had comparable with Prostatilen effect on the expression of oxidative stress - reduction of nitric oxide was 1.8 times, and TBA-RP - 1.9 times compared to control.

Under the influence of drug therapy Prostatilen noted a significant decrease of the output of prostatic isoenzyme of acid phosphatase (1.7 times) and increase of level of testosterone (1.6-fold) compared to control pathology.

Studied suppositories have had a more substantial impact on the activity of prostatic acid phosphatase (reduction of 2.4 times compared with the control, and 1.4 times in comparison with the reference product) and testosterone levels (an increase of 1.4 times).

Prostatilen have reduced levels of Ostrovidov the x protein ceruloplasmin (2.4 times) and C-reactive protein (1.8 times) in the blood.

Therapy investigational suppositories also contributed to the normalization of the level of ceruloplasmin (2.5 times) and in particular C-reactive protein (lower level 2.2 times).

As shown by morphological examination of the slices therapy drug compare Prostatilen contributed to the reduction of the inflammatory infiltration in the stroma of the gland acinar-to-find white blood cells. Signs of inflammation were noted in only 40% of surveyed male rats when viewing histological preparations. The remaining animals were observed normal structure of the tissue of the gland.

Studied suppositories had a similar Prostatilen action. Only 40% of the animals were observed foci of chronic prostatitis with inflammatory infiltration (mainly interstitial), occupying more than 1/4 slice of cancer. The remaining rats, the structure of the prostate gland was consistent with that of intact animals.

In General, the inventive pharmaceutical composition provides for the treatment of experimental prostatitis therapeutic effect, such Prostatilen or exceeding the action of Prostatilen.

Example 3. The effectiveness of suppositories in the rat model irritative vaginitis

Experiments were performed on 40 white mongrel rats-females weighing 180-200 g

Vaginitis was modeled by ADNOC atoi vnutrivlagalishnogo appliques irritant, which used a combination of gum turpentine with dimethylsulfoxide in the ratio of 1:1 dose of 0.5 ml/100 g body weight of the animal. 24 hours after the introduction of irritant started treatment of animals from the experimental group. The drug was administered in the vagina for 7 days at doses corresponding to a daily dose for a human. In terms of dosage form for rats daily dose amounted to 220 mg/kg of the drug was carried out 1 time per day. To prevent the free escape of suppositories for the vagina was temporaroly small cotton swab for 30 minutes.

Animals of the control group remained untreated. They recorded the dynamics of the inflammatory process, which evaluated the cellular composition of the vaginal smear and perform microbiological study of smears, fingerprints of the original, at 1, 3 and 7 days after application of irritant. During the same period were evaluated hematological markers of inflammation - content in peripheral blood leukocytes, leukocyte counts and erythrocyte sedimentation rate. In addition, monitor the behavior and General condition of the animals. Take into account also:

the severity of local hyperemia scoring: 0 - visible vaginal mucosa and the skin around the vagina with no changes; 1 - mild hyperemia of the visible mucous of the vagina; 2 points - severe hyperemia of mucous is vagina and the skin; 3-severe hyperemia of the mucosa of the vagina and the signs of self-harm skin-bites;

- the degree of ampleness vaginal scoring: 0 - no discharge; 1-weak selection pressure pad; 2 - moderate allocation, moistened skin around the vagina; 3 - copious, moistened skin around the vagina and litter.

Histological control was performed on 3, 7 and 10 day. For histological study in rats of the experimental and control groups were subjected to euthanasia using decapitate under light ether anesthesia.

Vagina were fixed in 10% formalin and after alcohol wiring embedded in paraffin. Sections were stained with hematoxylin-eosin and studied under a biological microscope MBI-6.

Animals from all experimental groups 24 hours after the introduction of irritant watched expressed concern, vaginal discharge and redness of the visible mucous membranes of the vagina.

In the first days after modeling vaginitis animals of the control group showed anxiety, increased reaction to external stimuli. They have a marked decrease in food and water consumption, the presence of tousled hair. All animals were observed sero-mucous discharge from the vagina. Deviations in the behavior of animals gradually decreased to 3-th day of the experiment. On the 7th day, the surface is Denia rats did not differ from the behavior of the intact (not participating in the experiment) animals.

The state and behavior of animals treated with investigational suppositories on the first day of the experiment, did not differ from the control group. They noted ruffled coat, increasing anxiety, aggressiveness in response to the grip. The drug was accompanied by anxiety and vocalization. On the third day of the introduction of vaginal suppositories marked decrease in vaginal discharge, decreased the severity of hyperemia. These changes were statistically significant compared with control. On the 7th day of the experiment, the visible symptoms of inflammation were stopped completely.

In the first days after initiation of therapy in all experimental groups was observed picture of acute inflammation with marked leukocytosis and shift leukocyte formula to the left to stab generation of leukocytes, lymphopenia. Noted high ESR.

Already on the first day of therapy with the investigational suppositories gave a positive result. In animals treated erythrocyte sedimentation rate was 1.3 times lower, the number of leukocytes was also decreased. This trend was observed throughout the experiment.

On the 3rd day, in the absence of positive dynamics in the control group of animals that were administered the investigational suppositories, noted a significant decrease in the number of leukocytes and segmented the tion of neutrophils, as well as reducing the severity lymphopenia compared with the first day since the beginning of therapy.

On the 7th day in the control group (without treatment) marked the beginning of a positive dynamics in relation to the studied parameters. In the group of animals treated with investigational suppositories, observed a significant decrease in the total number of blood leukocytes, a slight band shift, restored the number of neutrophils, lymphocytes. On the 7th day erythrocyte sedimentation rate was not different from that seen in intact animals.

Introduction irritant caused disturbances of the vaginal flora in animals from all experimental groups. In the control group during the whole experiment showed a significant change, indicating an inflammatory process is the high content of vegetative and revegetating forms of yeast, increasing the number diplokokkovyh and coccal flora in smears. Only on the seventh day of the experiment tended to normalize the microflora of the vagina.

Treatment with the study drug already on the 1st day led to a reduction in the number of diplococcus, yeast, gram-negative rods and gram-positive cocci. Under the influence of the studied suppositories animals on the third day restored the natural microflora composition (quantitative and qualitative characteristics), prakticheskie different from the scores in the norm. It should also be noted the increase of the number of lactic acid bacteria with high antagonistic activity against a wide range of pathogenic and conditionally pathogenic microbes, which determines the corrective effect of the drug in violation of bacteriocins.

Drug treatment for 7 days resulted in reduction of pathogenic flora in smears recovery microsense vagina. To the action of investigated suppositories were susceptible to both gram-positive and Grammatically cocci, Grammatically bacteria and vegetative and revegetative yeast.

Thus, the model irritative vaginitis study suppositories showed a pronounced antimicrobial effect. The treatment helped to restore the natural balance of vaginal microorganisms.

Morphological study of the sections of the vagina of rats with irritative the vaginitis was performed at 1, 3 and 7 days of the experiment.

The control rats during the first three days of the experiment was noted destructive and inflammatory changes in all layers of the vaginal wall. The superficial layer of the epithelium of the mucosa was in a state of necrobiosis, sometimes absent. Observed hyperchromatism nuclear membrane and lysis of chromatin. Polymorphonuclear leukocytes were unfilterable submucosal layer penetrated into the EPI is the men. In the deeper layers of submucosal layer watched the plethora and swelling of loose connective tissue. On the 3rd day of the processes of destruction are saved. A strong inflammatory reaction is characterized by massive infiltration of granular cells and the appearance of macrophages, lymphocytes and plasma cells. The 7th day of the experiment, changes in the mucous membrane of the vagina were slightly expressed: the epithelium of the mucous fully regenerates, the nuclei of epithelial cells were clear, plethora and edema, leukocyte infiltration of the submucosal layer is poorly expressed.

The treatment with investigational suppositories during the first three days allowed us to reduce the severity of inflammation of the mucosal epithelium. Necrobiosis cells were observed in the surface layers of the epithelium, also in the area of inflammation was infiltration by polymorphonuclear leukocytes, were found isolated polymorphonuclear leukocytes, lymphocytes and plasma cells.

Treatment with the study drug for 7 days led to a complete restoration of epithelial integrity, the histological structure of the vaginal mucosa did not differ from the mucous membrane of intact rats.

Obtained during histological research data, fully correlated with the results of the evaluation of hematological and microbiological markers is asplenia.

Thus, the claimed pharmaceutical composition effective for treatment of experimental vaginitis.

Clinical efficacy of suppositories was installed in the application of the sick men and women with diseases of the lower section of the genitourinary system.

Example 4. The effectiveness of suppositories in patients with chronic prostatitis

Study of the efficacy of clinical use of suppositories conducted in 22 patients with chronic prostatitis aged 25-47 years.

The main symptoms of chronic prostatitis were aching typical localization, various urination disorders, disorders of the ability to commit sexual intercourse and signs of neurotic state.

All patients had previously received conventional medications symptomatic and pathogenetic steps, where it was noted short-term therapeutic effect, requiring increased doses of treatment and a long reception. Suppositories used rectally at night before going to sleep within 10-15 days depending on the severity of the disease. The control group consisted of 10 similar patients who were prescribed conventional treatment.

The effectiveness of the treatment claimed by the suppositories were evaluated on the basis of the dynamics of complaints b is selected, clinical studies of blood and urine biochemical study of blood, the coagulation of the blood before and after treatment. The degree of abdominal pressure during urination and character of the urine stream expressed in points from 1 to 5 (1 = normal, 5 - highest change rate). Determine the maximum and average speed and time of urination, the time to reach the maximum speed of the urinary tract, estimated fluorometrically index. Along with the above research produced palpation assessment of the prostate gland, a laboratory study her secret, more in-depth study of the state of the copulative function. Also did an ultrasound of the prostate.

The main consideration when assessing the results of treatment of chronic prostatitis was paid to clinical criteria. After treatment, the pain completely disappeared at 72.4% and significantly decreased from 23.7% of the patients presenting complaints. From the number of patients suffering from sexual dysfunction, 52,6% indicated full recovery and 43.7% reported improvement. The positive effect of the suppositories was shown how to improve the quality of erections and enhance orgasm and eliminate his pain. There was also an increase in the duration of sexual intercourse. By the end of treatment 50,6% b is selected reported restoring libido.

Pollakiuriya (increases urination) completely stopped bothering with 85.4% of patients. Gone was the need for nighttime urination. Stranguria (difficulty urinating) ceased to bother 82,5%of patients, 22.9 per cent noted a distinct increase of the urine stream and relief act of urination.

Uroflometry recorded after treatment in patients with chronic prostatitis stage I and II, showed the restoration of the main parameters of urination to normal values. In stage III disease that prevented the decrease in elasticity of the bladder neck due to sclerotic changes in the tissue of the prostate, but they observed a distinct increase of the urine stream. Palpation of the prostate through the rectum was determined by the tendency to recover its size and consistency after treatment claimed by suppositories. Thus disappeared the parts of the seal, and the research itself was painless. The observed decrease in the size of the prostate gland, regarded as the result of a decrease in edema interstitial tissue and indicating the elimination of inflammatory activity in it, were confirmed by results of diagnostic ultrasound. Dynamic clinical and biochemical blood tests did not reveal any significant deviations from nor the social indicators. Side effects were not observed.

With the restoration of the function of the prostate gland under the influence of suppositories, there was an improvement in properties of its secret. This ensured the increase of the content of motile sperm in the ejaculate by 23.7%. Reduction of inflammatory activity was confirmed by reducing the number of leukocytes in the ejaculate, the prostate gland secretion and urine. At the same time decrease was observed in the studied material content of the deflated cells of the epithelium.

Example 5. The effectiveness of suppositories in patients of elderly and senile age with dysuric disorders

The study involved 49 patients with urination, including 29 men aged from 68 to 82 years and 20 women aged from 58 to 84 years. All patients of elderly and senile age complained of frequent urination up to 10-20 times a day, especially at night (up to 5-10 times), which significantly reduces the quality of life of older people and hampered their social adaptation.

The treatment efficiency was evaluated on the basis of the dynamics of the complaints of patients and the urodynamics. Determine the maximum, average speed and time of urination, the time to reach the maximum speed of the urinary tract, estimated uroflowmetry index.

Belnameda were randomly divided into 2 groups. The control group consisted of 18 people (11 men, 7 women)who received conventional therapy, including antispasmodic drugs (spasmes, spasma, spasmodically Neo) and cholinergic (detrusitol) actions.

Formed the core group of 31 patients (18 men, 13 women) were divided into 3 subgroups depending on the severity of urinary disorder. Patients, celebrating the most pronounced dysuric disorders in the form of increased frequency of urination up to 15-20 times a day, especially at night (up to 10 times), was appointed rectal suppositories in the morning and at night before going to sleep within 15 days.

When the average degree dysuric disorders (increased frequency of urination up to 10 times per day, including up to 5 times at night) patients received rectal suppositories at night before going to sleep within 15 days. Patients, celebrating moderate urinary disturbances, such as increased urination at night up to 5 times, used rectal suppositories at night before going to sleep within 10-15 days.

When comparing the patients in the control and main groups expressed positive trend was observed in the group of patients treated with suppositories.

In assessing the dynamics of subjective indicators all patients treated with suppositories, rated their condition as "superior". pollakiuria (increases urination) completely stopped worrying 76.5% of the patients of the basic group, in addition, they also have no need for nighttime urination. 13.2% of patients of the main group pollakiuriya significantly decreased to 7-8 times a day, and the need for nighttime urination decreased to 2-3 times.

Indicators of urodynamics in patients of elderly and senile age with dysuric disorders after using the pharmaceutical compositions in the form of suppositories presented in the table.

It should be noted that patients in the control troupe was not observed positive dynamics of the bladder both subjective and objective indicators, despite the use of conventional tools.

Patients in the control group who received conventional therapy, uroflowmetry index virtually unchanged after treatment.

In the group of patients of the main group treated with the claimed suppositories, uroflowmetry index increased almost in 2 times, which confirms their positive influence on the nature of urination.

Uroflowmetry recorded after treatment in patients for whom ilago and senile age with moderate dysuric disorders showed restoration of the basic parameters of urination to normal values under the action of suppositories.

In elderly patients with severe manifestations of dysuric disorders full normalization of urination prevented the age-related decline in the elasticity of the bladder neck, but, nevertheless, these patients treated with suppositories, there was a marked strengthening of the urine stream and reduced daytime urination up to 7-8 times, and in the night - up to 2-3 times.

These data indicate therapeutic efficacy suppositories when applied rectally in 10-15 days depending on the severity of the disease and the feasibility of their use in the treatment of patients with dysuric disorders of various origins in order to restore the functional activity detrusor-sphincter system of the urinary bladder.

Example 6. The effectiveness of suppositories for the treatment of urogenital disorders in women in peri - and postmenopause

Treatment with the use of suppositories held on 24 women aged 46-55 years with urogenital disorders in peri - and postmenopausal women. Patients complained of hot flashes heat to the head and upper body, rash, irritability, emotional labels the industry. It was noted the symptoms of vaginal atrophy (dryness and itching in the vagina, dyspareunia, recurrent vaginal discharge) and cystourethroscopy atrophy (frequent daytime (pollakiuriya) and night (nocturia) urination, cystalgia, imperative (urgent) urination).

Declare suppositories used vaginally at night before going to sleep within 25-30 days.

It was found that after using suppositories in 83% of patients were stopped subjective symptoms vaginal (dryness and itching in the vagina, dyspareunia, bleeding etc) and cystourethroscopy atrophy (pollakiuriya, nocturia, urgent desires and so on). These symptoms disappeared in the perimenopausal and postmenopausal periods. The vaginal health index was increased in women up to 4-5 points, the value of the maturity of the vaginal epithelium was increased to 57-79% (appeared intermediate and superficial cells), normalized colposcopic picture.

For stress urinary incontinence in perimenopause on the background monotherapy suppositories symptoms completely disappeared in 27% of women.

In other forms of dysuric disorders from the beginning it was used combined treatment suppositories and hormone replacement therapy, behavioral therapy, M-cholinolytics, selective serotonin reuptake inhibitors serot is Nina). When such treatment a good effect was achieved in 82% of patients: the patients was 2.5 times decreased frequency of daytime and night time urination, in 93% of cases were stopped imperative incontinence.

Thus, the results obtained indicate normalizing effects of suppositories on the structures of the urogenital tract, consisting in the improvement of the trophic and proliferation of the epithelium, as well as the normalization of the contractile activity of the detrusor due to an improved blood supply.

Declare suppositories it is advisable to apply with curative purpose in combination with any symptomatic and pathogenetic therapy used for the treatment of urogenital disorders in peri - and postmenopausal women.

As studies have shown, the inventive pharmaceutical composition in the form of suppositories was effective not only in treating diseases of the prostate gland (as a mixture of bioregulatory peptides of the prostate gland of cattle), but also in other diseases of the pelvic organs not only men but also women.

1. Pharmaceutical composition for the treatment of diseases of the lower section of the genitourinary system in the form of suppositories comprising the bioactive compound and a fatty base, characterized in that as bioactive the th compound composition contains a mixture of amino acids: glutamic acid, lysine, alanine, arginine and glycine and optionally zinc in the form of zinc chloride in the following ratio of components in the composition in grams per one suppository mass of 2.7-2.9 g:

2. The pharmaceutical composition according to claim 1, characterized in that it further comprises 10-30 µg of selenium in the anhydrous form of sodium Selenite.

3. The pharmaceutical composition according to claim 1, characterized in that it further comprises at 0.020-0.035 g of sodium femoropatellar.