RU2798677C2 - Method of treatment of stress urinary intention in women - Google Patents

Abstract

FIELD: medicine; urology; gynecology.

SUBSTANCE: against the background of physiological filling of the bladder, a transurethral injection of a heterogeneous gel into the paraurethral tissues of the proximal part of the urethra, using a fibroureteroscope or a rigid urethrocystoscope, is performed at three points, as in figure 1: along the lateral and lower walls of the urethra to a depth of 3 mm, until the formation of papules of the bulk-forming substance heterogeneous gel with a total volume of 1–3 ml, with a particle size of 150 to 300 micrometers, containing 30% collagen-containing extract and 70% monosaccharides.

EFFECT: method allows to reduce the time of treatment of patients, minimize possible risks and avoid complications associated with surgical treatment, improve the quality of life of patients, reduce economic costs by reducing the treatment time.

1 cl, 1 dwg, 2 ex

Description

The method relates to medicine, in particular to therapy, namely the treatment of clinically manifested stress urinary incontinence in women.

The main clinical manifestations of stress urinary incontinence are drip urinary incontinence during exercise, sneezing, coughing, etc. Stress urinary incontinence leads to the need to use personal hygiene and urological rehabilitation products: gynecological and urological pads, absorbent underwear.

Stress urinary incontinence is an urgent problem of modern society that significantly affects various aspects of the quality of life of women: social, physical, emotional, sexual, which ultimately leads to the development of a persistent depressive syndrome (Fry, C.H., Meng E., and Young J.S. The physiological function of lower urinary tract smooth muscle, Auton Neurosci 154:3–13, 2010). About 127 million women and 10 million men suffer from symptoms of stress urinary incontinence worldwide, and this figure is projected to increase to 167 million in the coming years (Irwin, D.E., Kopp Z.S., Agatep B., Milsom I., and Abrams P. Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction BJU Int. 108:1132–1138, 2011).

According to generally accepted standards, first-line therapy for the treatment of mild forms of stress urinary incontinence includes such methods as: pelvic floor muscle training, biofeedback and behavioral therapy (DeMaagd, G., and Davenport T. Management of urinary incontinence. Pharm. Ther. 37 :345–361, 2012). Pharmacotherapy in the treatment of stress urinary incontinence does not lead to satisfactory clinical results. The use of oral / transvaginal estrogen-containing drugs in many studies has not proven to be an effective method of treatment. Drugs of the serotonin reuptake inhibitor group lead to an increase in the tone of the striated urethral sphincter, however, they are currently not encouraged for use in stress urinary incontinence (Phé V., Nguyen K., Rouprêt M., Cardot V., Parra J., and Chartier-Kastler E. A systematic review of the treatment for female stress urinary incontinence by ACT® balloon placement, Uromedica, Irvine, CA, USA). World J Urol. 32:495–505, 2014). In the absence of the effect of conservative therapy, the method of choice is surgical treatment - sling urethropexy (Lucas, M. G., Bosch R.J.L., Burkhard F.C., Cruz F., Madden T. B., Nambiar A.K., Neisius A., et al. EAU guidelines on surgical treatment of urinary incontinence. Eur Urol 62(6):1118–1129, 2012). Despite the fact that this method is the "gold standard" for the treatment of stress urinary incontinence, it has a number of significant disadvantages: urethral pain syndrome, chronic urinary retention, dyspareunia, the need for anesthesia (Kennelly, M. J., and Myers E.. Single-incision slings, In: Smith's Textbook of Endourology, edited by A. D. Smith, G. Preminger, G. Badlani, and L. Kavoussi, Hoboken: Wiley-Blackwell, 2011, pp. 1672–1683).

Based on the foregoing and analyzing the presented methods of treatment of stress urinary incontinence (with the exception of experimental technologies), it becomes necessary to search for minimally invasive, effective, not requiring anesthesia, not leading to the development of secondary complications, treatment methods. One such approach is the use of paraurethral bulking agents to reduce or eliminate urinary incontinence.

Currently, there are several bulk-forming drugs used in the treatment of stress urinary incontinence, on the basis of which the concept of an “ideal material” for a bulk-forming substance was formed: easy conductivity through the injection needle, long-term preservation in the tissue structure, biocompatibility, cancer negativity, absence of allergic reactions, in addition, the substance should not migrate in body tissues (Herschorn S. Current use of injectable agents for female stress urinary incontinence. Rev. Urol. 7:S12–S21, 2005).

The closest (prototype) is a bulking drug based on bovine collagen (Ghoniem, G., and Boctor N. Update on urethral bulking agents for female stress urinary incontinence due to intrinsic sphincter deficiency. J. Urol. Res. 1:1009, 2014 ).

However, due to the high frequency of migration of the injected substance, allergenicity and high cost, the production of the drug was suspended.

For bulk-forming substances from autologous fat, the frequency of migration and fat embolism was extremely high, which prevented their continued use in wide practice.

All synthetic drugs based on inert polymers (calcium hydroxylapatite, polydimethyloxane, polyacrylamide) have found wider application in the treatment of stress urinary incontinence, however, none of them corresponded to the “ideal material” formula, which forced the search for an effective and high-quality drug for treatment stress urinary incontinence.

Almost all surgical methods of treatment carry anesthetic risks, are dangerous for the development of pain, bleeding, inflammation, and can lead to a decrease in the quality of urination, which, in general, reduces the quality of life of patients. Conservative medical methods require improvement.

The technical solution is the transurethral injection into the paraurethral tissues of the proximal part of the urethra of a biopolymer heterogeneous gel with high regenerative properties to reduce the severity or completely eliminate the symptoms of stress urinary incontinence in women.

The technical solution is achieved by the fact that, as well as in the known method (prototype), bulk-forming substances are introduced.

A feature of the proposed method is that, against the background of physiological filling of the bladder, a transurethral injection of a heterogeneous gel into the paraurethral tissues of the proximal part of the urethra, using a fibroureteroscope or a rigid urethrocystoscope, is performed at three points, as in figure 1: along the side and lower walls of the urethra to a depth of 3 mm, until the formation of papules of a bulk-forming substance of a heterogeneous gel with a total volume of 1-3 ml, with a particle size of 150 to 300 micrometers, containing 30% collagen-containing extract and 70% monosaccharides.

The peculiarity of this volume-forming substance can be attributed to its ability to be replaced by paraurethral tissues during resorption, capable of maintaining the locking functions.

The method of treatment is explained by a detailed description, clinical examples and an illustration, which shows:

Fig. 1 - scheme of drug administration: x - injection points.

The method is carried out as follows.

Method of administration of the drug: on an outpatient basis in compliance with the rules of asepsis and antisepsis against the background of physiological filling of the bladder (300-400 ml.) -3 ml (depending on the severity of stress urinary incontinence and anatomical features) at three points (Figure 1), remote at different distances from the neck of the bladder, along the side and lower walls of the urethra, to a depth of 3 mm., Before the formation of volume-forming papules heterogeneous gel substance containing: collagen-containing extract 30% (peptides of partially hydrolyzed collagen; proteoglycans (hyaluronic acid, chondroitin-4-sulfate, chondroitin-6-sulfate, dermatan sulfate, heparin, heparan sulfate, glycoproteins, proteins - antibodies, interferons, proteins complement and blood plasma systems, receptor proteins, monosaccharides (glucose, fructose, mannose, glucosamine, galactosamine, fructosamine, sialic acid)) and cross-linked and micronized collagen particles 70%, with a particle size of the administered drug of 100-300 micrometers.

After administration of the bulk-forming agent, the short-term observation period should be 1-2 hours. Control examination should be carried out 2-3 days after the manipulation.

Clinical examples.

Example 1

Patient S., born in 1974, is observed with a diagnosis of stress urinary incontinence. The patient complains of dripping urine during exercise, coughing, sneezing. From the anamnesis it is known that the patient performed pelvic floor muscle training for more than 12 months and took m-cholinolytic drugs for more than 3 months without effect.

On examination, there is no prolapse of the genitals. The diagnosis was confirmed by a cough test and urodynamic research methods. Drip leakage of urine was revealed at Pdet=47 cm H ₂ O on the bladder filling volume of 286 ml. The maximum mean intraurethral pressure during profilometry of the urethra was 36 cm H ₂ O.

On examination:

1. Diary of urination:

1. One hour Pad-test: 12g

2. Visual analogue scale: 65mm.

Based on the results of the history taking, assessment of complaints and clinical and instrumental examination, the severity of urinary incontinence in the patient was assessed as moderate. She completed the introduction of bulk-forming substances according to the above method.

Against the background of physiological filling of the bladder (350 ml) after application anesthesia with a preparation based on 20% benzocaine, the introduction was performed under visual control, using a fibroureteroscope, at three points, remote at different distances from the bladder neck along the lateral and lower walls of the urethra (Fig. .1), to a depth of 3 mm, with a total volume of 1 ml, until the formation of papules of a bulk-forming substance of a heterogeneous gel, containing: collagen-containing extract 30% (peptides of partially hydrolyzed collagen; proteoglycans (hyaluronic acid, chondroitin-4-sulfate, chondroitin-6 -sulfate, dermatan sulfate, heparin, heparan sulfate, glycoproteins, proteins - antibodies, interferons, proteins of the complement system and blood plasma, receptor proteins; monosaccharides (glucose, fructose, mannose, glucosamine, galactosamine, fructosamine, sialic acid)) and cross-linked and micronized particles collagen - 70%, with a particle size of the injected drug 100-300 micrometers.

After administration of the bulk-forming substance, the short-term observation period was 2 hours. The control examination was carried out 3 days after the manipulation.

After 14 days from the moment of administration of the volume-forming substance, a significant improvement in the general well-being of the patient was noted.

During the control examination:

Subjectively, the patient noted the absence of drip urinary incontinence. The maximum rate of urination according to uroflowmetry was 21 ml/s, the volume of excreted urine was 298 ml, the volume of residual urine was 12 ml.

1. Diary of urination:

De novo bladder overactivity was not detected.

2. One hour Pad-test: 0g

3. Visual analogue scale: 0 mm.

Thus, the patient, thanks to the proposed method, achieved a complete cure.

Example 2

Patient T., born in 1987, is observed with a diagnosis of stress urinary incontinence. The patient complains of dripping urine during exercise, coughing, sneezing, especially aggravated by sexual contact. For the first time complaints arose after the first birth. Childbirth is uncomplicated. Fetus - 1. Weight - 3650 g. After childbirth within 6 months. the patient used pads, applied Kegel exercises. The effect of treatment was not achieved. When examined at the place of residence, the patient was offered a sling urethropexy, which she refused due to the possible development of side effects in the form of dyspareunia.

On examination, there is no prolapse of the genitals. The diagnosis was confirmed by a cough test and urodynamic research methods. Drip leakage of urine was revealed at Pdet=59 cm H ₂ O on the bladder filling volume of 357 ml. The maximum mean intraurethral pressure during profilometry of the urethra was 42 cm H ₂ O.

On examination:

1. Diary of urination:

2. One hour Pad-test: 19g

3. Visual analogue scale: 77mm.

According to the results of the history taking, assessment of complaints and clinical and instrumental examination, the severity of urinary incontinence in the patient was assessed as severe. She completed the introduction of bulk-forming substances according to the above method.

Against the background of physiological filling of the bladder (350 ml) after application anesthesia with a drug based on 20% benzocaine, the introduction was performed under visual control using a rigid fibroureteroscope at three points, remote at different distances from the bladder neck along the lateral and lower walls of the urethra (Fig. 1), to a depth of 3 mm, with a total volume of 3 ml, until the formation of papules of a bulk-forming substance of a heterogeneous gel, containing: collagen-containing extract 30% (peptides of partially hydrolyzed collagen; proteoglycans (hyaluronic acid, chondroitin-4-sulfate, chondroitin-6- sulfate, dermatan sulfate, heparin, heparan sulfate, glycoproteins, proteins - antibodies, interferons, proteins of the complement system and blood plasma, receptor proteins; monosaccharides (glucose, fructose, mannose, glucosamine, galactosamine, fructosamine, sialic acid)) and cross-linked and micronized collagen particles - 70%, with a particle size of the injected drug 100-300 micrometers.

After administration of the bulk-forming substance, the short-term observation period was 2 hours. The control examination was carried out 3 days after the manipulation.

After 14 days from the moment of administration of the volume-forming substance, a significant improvement in the general well-being of the patient was noted.

During the control examination:

Subjectively, the patient noted a significant decrease in urinary incontinence, episodes of which appear only with active sports. There were no episodes of urinary incontinence during sexual intercourse. The maximum rate of urination according to uroflowmetry was 19 ml/s, the volume of excreted urine was 397 ml, the volume of residual urine was 26 ml.

1. Diary of urination:

De novo bladder overactivity was not detected.

2. One hour Pad-test: 2g

2. Visual analog scale: 31mm.

Thus, thanks to the proposed method, the patient achieved a significant improvement, which made it possible to maintain a good quality of life.

The use of the developed method in the clinic has medical, social and economic significance, is effective and safe, is simple, easy to perform, which allows it to be widely used in the practice of a urologist on an outpatient basis.

The proposed method allows:

- reduce the time of treatment of patients, minimize possible risks and avoid complications associated with surgical treatment;

- improve the quality of life of patients;

- reduce economic costs by reducing treatment time.

Claims (1)

A method for the treatment of stress urinary incontinence of mild and moderate severity in women, including the introduction of volume-forming substances, characterized in that, against the background of physiological filling of the bladder, a transurethral injection of a heterogeneous gel into the paraurethral tissues of the proximal part of the urethra is performed using a fibroureteroscope or a rigid urethrocystoscope, at three points , as in figure 1: along the lateral and lower walls of the urethra to a depth of 3 mm, until the formation of papules of a bulk-forming substance of a heterogeneous gel with a total volume of 1-3 ml, with a particle size of 150 to 300 micrometers, containing 30% collagen-containing extract and 70% monosaccharides.

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