EA034382B1 - Medicinal product in complex therapy of chronic cystitis and method of complex therapy of chronic cystitis - Google Patents

Abstract

The invention relates to the field of pharmaceutics and medicine, namely to the use of a medicinal product hydroxyethyldimethyldihydropyrimidine as a medicament in the complex therapy of chronic cystitis, and to a method of the complex therapy of chronic cystitis using hydroxyethyldimethyldihydropyrimidine.

Description

The invention relates to the field of pharmaceuticals and medicine, in particular to the use of the drug hydroxyethyl dimethyldihydropyrimidine as a medicine in the complex therapy of chronic cystitis, as well as to a method for the complex treatment of chronic cystitis using hydroxyethyl dimethyldihydropyrimidine.

Cystitis is a serious women's health problem characterized by infectious inflammatory changes in the bladder wall with a primary lesion of its mucous membrane [1].

The problem of treating cystitis in women has important social significance: 57% of patients are of working age, 40% of the duration of the disease varies from 1 to 5 years, and the average age is 35 years.

The most common (80-90%) microbial pathogen is E. coli, which has high pathogenic and adaptive capabilities, causing the adhesion phenomenon, has a high reproduction rate, causes the production of ammonia, weakening the immune system and disrupting the function of smooth muscle fibers of the urinary tract.

According to the clinical course, cystitis can be acute and chronic. The most difficult in terms of treatment is the chronic form of the course. Unfortunately, 40% of women do not seek timely medical attention, considering cystitis a trifling disease. In addition, untimely and inadequate treatment creates the conditions for frequent relapse. It is known that after completion of treatment, 60% of women report a relapse of the infection within 3-4 months. It should be noted that women with symptoms of cystitis, not wanting to spend time visiting a doctor, use the recommendations of pharmacists, which certainly affects the results of treatment.

In a quarter of cases, relapse occurs due to ongoing adhesion of bacteria (penetration into the submucosal layer). Adhesion of microorganisms is carried out in two stages:

stage - glycocalyx damage and contact with the cell membrane (initial stage);

stage - the existence of bacteria as a single complex (glycocalyx) with the host cell (persistence).

Persistence is the basis of asymptomatic bacteriuria and intermittent aggression of microorganisms against host cells, causing a relapse of chronic cystitis.

The role of microorganisms in the genesis of chronic cystitis is a violation of the structure of collagen fibers of the connective tissue of the lamina propria mucosa and submucosal layer. As a result, the glycosaminoglycan layer is depolymerized, the vascular permeability and microcirculation of the mucous and submucosal layers are disturbed, leading to the destruction of urotheliocytes. Restructuring of connective tissue is a springboard for the development of hyperplastic, proliferative, metaplastic and diplastic changes in the transitional epithelium in chronic cystitis.

The prior art comprehensive approach to the treatment of recurrent urinary tract infections, which consists in the appointment of antibiotic therapy, the use of glycosaminoglycan layer stabilizers, immunotherapy and the use of herbal remedies.

However, it is not always possible to use expensive drugs in the treatment of chronic cystitis, therefore, in urological hospitals, it is more often used, in addition to antibacterial and vascular therapy, topical treatment - instillations in the bladder of a solution of a compound - a derivative of silver, for example collargol (the closest analogue of the invention is the prototype) .

Collargol is a silver-based drug with an antiseptic effect. The drug has anti-inflammatory, bactericidal, astringent (decrease in mucus production) action. It contains 70% silver and 30% albumin, which is designed to connect silver molecules to each other and maintain them in an active state. For instillation, a 1% aqueous solution with an exposure of 15-20 minutes is used.

The disadvantage of the old, long-standing method of treating chronic cystitis using the collargol instillation is that the collargol solution causes a burn of the mucous membrane of the bladder of the mild degree and its recovery after local treatment takes a long time, which certainly affects the preservation of frequent urination and even more sharp that time after treatment.

The technical problem to which the invention is directed is the development of a new, effective method for the treatment of chronic cystitis using a well-known drug devoid of the lack of a prototype.

The technical result of the invention is:

1. Strengthening the process of regeneration of the mucous membrane of the bladder, leading to an improvement in the condition of the mucous membrane of the bladder and urination.

2. The implementation of the new appointment of a known drug.

The technical result of the invention is achieved by the inclusion in the complex therapy of cystitis of a well-known drug with the international nonproprietary name - hydroxyethyl dimethyldihydropyrimidine. The trade name of the drug in the form of tablets,

- 1 034382 produced in Russia from the specified active substance, registered in various countries of the world as a trademark - Xymedon. There are no generics of the drug Ximedon in the world.

Hydroxyethyl dimethyldihydropyrimidine accelerates tissue regeneration processes and reduces the healing time of the burn surface, improves the healing of skin grafts with autodermoplasty. Helps to normalize the ratio between the content of fibrinogen in the blood and its fibrinolytic activity. Improves regional blood circulation. It normalizes the immune system, increases the phagocytic activity of T-lymphocytes and nonspecific resistance of the body. It stimulates erythro- and leukopoiesis, cellular and humoral defense factors, and has anti-inflammatory and antimicrobial effects [2].

To date, the use of hydroxyethyl dimethyldihydropyrimidine in urology for the treatment of cystitis is not known.

The authors of the present invention, taking into account the properties of hydroxyethyl dimethyldihydropyrimidine as a medicine that enhances the regeneration process, which has both bactericidal and bacteriostatic effects, suggested that the inclusion of hydroxyethyl dimethyldihydropyrimidine in the complex treatment of chronic cystitis will accelerate the process of regeneration of the mucous membrane of the urinary bladder with antimycol drugs and antimycol solution.

To conduct a clinical study on the basis of the urological clinic im.A.V. Vishnevsky, Kazan, were selected 30 patients with a confirmed diagnosis of chronic cystitis with a relapse rate of at least three times a year at the age of 20 to 70 years. The average age was 46.0 ± 2.7 years (Table 1).

Table 1. The distribution of patients by age

Age years Number of persons The proportion in the group,% 20-29 5 16 30-39 5 16 40-49 eleven 38 50-59 3 10 60 years and older 6 20

In most patients (70%), the disease arose between the ages of 25 and 50 years (working age), characterized by a duration of 1-15 years (Table 2) with a relapse rate of 3 to 7 episodes. The duration of the maximum without recurrent course was 6 years, the minimum 2-3 months. Table 2. Duration of chronic cystitis

Criteria Number of persons The proportion in the group,% Up to 5 years 12 40 Up to 10 years 5 16 More than 10 years thirteen 44

The characteristics of the complaints of patients are presented in table. 3.

Table 3. Characterization of complaints in examined women before treatment

Symptoms The number of patients The proportion of complaints in the group,% Rapid urination 27 90 Imperative urge 16 53 Pain during urination 26 87 Nocturia 23 77 Burning sensation 14 47 Feeling of incomplete emptying 17 57

As can be seen from the table. 3, the main complaints of patients were rapid and painful urination with a burning sensation and incomplete emptying of the bladder. Increased nighttime urination (nocturia) occurred in 77% of patients, which affected the general well-being.

Laboratory studies conducted by all patients before treatment did not reveal pathological changes in the clinical blood test.

When examining urine, changes were found that are characteristic of an infectious and inflammatory process in the organs of the urinary system (Table 4).

- 2 034382

Table 4. Laboratory diagnosis of chronic cystitis

Indicators Number of Patients Specific weight% leukocyturia 23 78 microhematuria eleven 36 macrohematuria 2 8 proteinuria 24 81 alkaline urine reaction 26 86 uric acid reaction 4 14

According to the table. 4 in the general analysis of urine in 23 (78%) patients, the leukocyte count was more than 12 in the field of view; in the analysis of urine according to Nechiporenko, the content of leukocytes is from 5 to 12 thousand in 1 ml .; in 11 people (36%), the presence of red blood cells was noted.

According to the results of bacteriological studies, it was found that more often the causative agent of the infectious and inflammatory process in the bladder was E. coli - 38%, although other microflora were also sown, six patients did not have microflora. (table 5)

Table 5. The results of bacteriological studies

Pathogen The number of patients Specific weight% E.Coli eleven 38 Staphylococcus 6 20 Klebsiella 3 10 Enterococcus 2 6 Other 2 2

Patients were treated as follows. Antimicrobials (antibiotics and / or antibacterial drugs) were prescribed in accordance with the sensitivity to the drugs, or antimicrobials recommended by the Federal Clinical Recommendations were used (T. Perepanova, 2015)

Next, local treatment was prescribed - instillation with a solution of a silver derivative, and then the drug Ximedon with the active substance hydroxyethyl dimethyldihydropyrimidine was taken in an amount of 1.5 g per day (500 mg 3 times a day) for 30 days.

15 days after the start of treatment, the patients underwent an intermediate control. Two weeks after the start of treatment, there was already a positive trend in the symptoms, laboratory tests and other methods of follow-up examination.

After 30 days, all 30 patients completed the treatment. A follow-up examination after 30 days made it possible to establish that the complex therapy of chronic cystitis according to the above treatment regimen with the inclusion of the drug hydroxyethyl dimethyldihydropyrimidine with the aim of regenerating the bladder mucosa was effective. No adverse events associated with the use of the drug Ximedon, not identified. Complaints characteristic of cystitis are absent.

In the table. 6 shows the dynamics of changes in indicators before treatment during treatment and after treatment, illustrating the effectiveness of the treatment using the drug hydroxyethyl dimethyldihydropyrimidine.

Table 6. Evaluation of the effectiveness of treatment

Indicator Value to treatment Value 15 days after starting treatment Value 30 days after starting treatment The coefficient of significance of changes (P) The number of urinations, times 12.3 ± 2.1 9.1 ± 1.2 6.4 ± 1.2 <0.001 Nocturia, times 3.3 ± 0.8 1.2 ± 0.5 - The number of urgent calls for urination times 6.2 ± 1.4 2.7 ± 1.2 Urine volume (the amount of urine excreted at one urination), ml 84.1 ± 2.3 128.6 ± 3.6 147.9 ± 26.7 <0.001 The volume of residual urine, ml 65.2 ± 21.6 56.0 ± 11.2 12.0 ± 11.1 <0.001 Bladder wall thickness (according to ultrasound), mm 6.4 ± 0.2 5.3 ± 0.6 3,5 ± 3

- 3 034382

According to the table. 6, the number of urinations was halved (from 12.3 ± 2.1 to 6.4 ± 1.2) and corresponds to normal daily values. There are no urgent urges, urinary incontinence and nighttime urination (nocturia). The average volume of residual urine in most patients decreased three times. The bladder wall thickness in the filled state decreased almost twice and corresponds to normal values (3.5 ± 3).

The effectiveness of the treatment of chronic cystitis with the inclusion of hydroxyethyl dimethyldihydropyrimidine in the complex therapy was analyzed in comparison with the traditional method of treatment mentioned above - the use of an antimicrobial preparation in combination with the instillation of a solution of a silver derivative compound in the bladder.

In the urological clinic named after A.V. Vishnevsky, Kazan, has accumulated a large body of static information on the treatment of patients in the traditional way, including the administration of an antimicrobial preparation and the installation of a solution of a silver derivative compound in the bladder. Such patients had relapses 2-3 times a year and were repeatedly admitted to a urological clinic during periods of recurrence of the inflammatory process. To evaluate the effectiveness of treatment in comparison, several criteria were selected (by which a comparison can be made correctly): the number of urination, nocturia (the number of urination at night), the number of urgent urination, hyperemia, leukocyturia (Table 7).

Table 7. Comparative analysis of the results of treatment of chronic cystitis with and without hydroxyethyl dimethyldihydropyrimidine (main group) (control group)

Indicators Control group Main group In 15 days After 30 days In 15 days After 30 days The number of urinations, times 10.1 ± 1.7 9.1 ± 1.9 9.1 ± 1.2 6.4 ± 1.2 Nocturia, times 3.4 ± 0.7 1.6 ± 1.7 1.2 ± 0.5 0 Urgent urination, times 7.1 ± 1.1 5.2 ± 0.8 2.7 ± 1.2 0 Urine volume (amount of urine excreted at one urination), ml 96.2 ± 4.3 107.9 ± 3.9 128.6 ± 36 147.9 ± 26.7 Hyperemia, the number of patients 24 7 0 0 Leukocyturia, the number of patients 24 3 5 0

As can be seen from the table. 7, the number of urinations after 30 days of treatment in the main group is 6.4 ± 1.2 times, while in the control group 9.1 ± 1.9 times. The main group has no night and urgent urination, there is no hyperemia and leukocyturia, which in combination indicates a higher treatment efficiency in the main group of patients compared with the control group.

In patients of the control group, relapse occurred 2-3 times a year. In patients of the main group who took hydroxyethyl dimethyldihydropyrimidine, no relapse was recorded 10 months after the start of treatment.

Thus, we can conclude that the technical result of the invention is achieved - a new purpose of the well-known drug hydroxyethyl dimethyldihydropyrimidine in the complex treatment of chronic cystitis is realized. A new method of treating chronic cystitis accelerates the process of regeneration of the mucous membrane of the bladder, which leads to an improvement in the condition of the mucous membrane of the bladder and indicators of urination.

List of used literature:

1. Report on the clinical study of the drug Ximedon "in the treatment of chronic cystitis in women (the main coordinator is Professor M.E. Sitdykova).

2. Instructions for use of the drug Ximedon.

Claims (8)

CLAIM 1. The use of hydroxyethyl dimethyldihydropyrimidine in an amount of 1.5 g per day as a medicine in the treatment of chronic cystitis. 2. The use according to claim 1, characterized in that the hydroxyethyl dimethyldihydropyrimidine is taken at 0.5 g three times a day. 3. The use according to claim 1 or 2, characterized in that the hydroxyethyl dimethyldihydropyrimidine is taken orally. 4. The use according to claim 3, characterized in that the hydroxyethyl dimethyldihydropyrimidine is taken in tablet form. 5. A method for the treatment of chronic cystitis, comprising administering to the patient an effective amount of an antimicrobial drug, instilling a solution of a silver derivative compound into the bladder, characterized in that it further comprises administering 1.5 g per day of hydroxyethyl dimethyldihydropyrimidine to the patient. 6. The method according to claim 5, characterized in that the hydroxyethyl dimethyldihydropyrimidine is administered 0.5 g three times a day. 7. The method according to claim 5 or claim 6, characterized in that the hydroxyethyl dimethyldihydropyrimidine is administered orally. 8. The method according to claim 7, characterized in that the hydroxyethyl dimethyldihydropyrimidine is administered in the form of tablets.