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Urolithiasis is a worldwide problem that has arisen in humans for many centuries. the annual incidence of urolithiasis in Western countries is about 10-15%, and in the Middle East ranges from 20-25% (uthaya chandirika jayaraman et al., 2018).

The prevalence of pathology is quite high in countries with a high standard of living, for example, in Canada, Sweden and the United States of America (10%) (Türk C. et al., 2016).

Urolithiasis, or urolithiasis, is a disease characterized by metabolic imbalance and the formation of calculi in any part of the urinary system. It occurs most often as a result of structural and functional changes in the urinary tract, a hereditary predisposition, diseases of the endocrine system (Alyaev Y.G. et al., 2014).

Urinary stone is an organic deposit of a solid consistency, it contains minerals and salts that are formed in the renal parenchyma, renal pelvis and bladder. Small-sized stones are removed from the body with a stream of urine, which is absolutely painless for a person, but if the size of the stone is larger than the lumen of the ureter or urethra, it can injure their walls and cause a pronounced pain syndrome, which is called "renal colic." In some cases, the stone can stop in the lumen of the ureter or urethra and cause a complete stop of the outflow of urine - occlusion of the urinary tract. This condition requires immediate surgical intervention.

By localization, there are: stones of the cups, stones of the renal pelvis, stones of the ureters, stones of the bladder, stones of the urethra.

Stones can be divided into groups by size: A - up to 5 mm; B - 5-10 mm; C - 10–20 mm; D - more than 20 mm. They are also classified due to the formation of: infectious nature, non-infectious nature, due to hereditary conditions (genetic) or formed due to the intake of certain drugs (drugs) (Türk C. et al., 2016).

The group of non-infectious stones includes calcium oxalates, calcium phosphates and uric acid stones. Infectious stones contain: magnesium and ammonium phosphates, carbonatapatite, as well as ammonium urate. Stones formed for genetic reasons - cystine, xanthine and 2,8-dihydroxyadenine.

The process of stone formation in the urethra, as a rule, takes more than one year. There are many theories of the starting mechanism of stone formation.

1. Matrix theory - infectious processes cause the active death of epithelial cells, on which salts are adhered.

2. Colloid or protein theory - protective proteins change from a lyophilic state (ability to attract liquid) to a lyophobic state (ability to repel liquid), creating favorable conditions for crystallization of urine salts.

3. The ionic theory is based on the insufficiency of urine proteolysis, which under conditions of an altered pH leads to stone formation.

4. The theory of precipitation and crystallization considers the formation of stone during the supersaturation of urine with ions, which starts the crystallization process (Buck A., 1990).

5. The inhibitory theory explains the formation of stones by the imbalance of inhibitors and promoters that maintain the stability of a homogeneous urine composition (Sommeren A., 1989; Alyaev Y.G. et al., 2014).

Nevertheless, the further process of stone formation occurs according to one scenario. It consists of the following stages:

1) nucleation - the union of ions into microscopic particles, or their deposition on fragments of the epithelium, protein.

2) aggregation is a process in which crystals agglomerate, which are transformed in a free solution into larger multicomponent particles, the connection of primary crystals with each other. They are attached to each other due to proteins, lipids, polysaccharides, etc.

3) further crystal growth (Clin Rev Bone Miner, 2011).

There are two systems that are antagonists - lithogenic (contributing to the formation of stones) and antilithogenic.

The lithogenic system includes uric acid concentration and urine pH.

Uric acid is directly involved in the process of attachment of calcium oxalate to epithelial cells.

Urine pH directly affects stone formation. High acid urine precipitates uric acid crystals and also stimulates the crystallization of calcium oxalate. Highly alkaline urine can precipitate calcium phosphate and thereby contribute to the secondary nucleation of calcium oxalate. It is believed that the risk of stones is minimal when the pH of urine is in the range of 5.8–6.2.

Antilithogenic factors include small organic anions such as citrate, pyrophosphates, magnesium cations, and the Tamm – Horsfall protein (Clin. Rev. Bone Miner., 2011).

Some types of stones are amenable to drug therapy, more precisely chemical elimination, while others need to be removed surgically. Trinefron - multicomponent drug. Centaurium erythraea grass, root lovage (Levisticum officinale), rosemary leaves (Rosmarinus officinalis) are included in its composition.

Trinephron successful prevention and reduction of gestational pyelonephritis in pregnant women. In addition, the drug Trinefron actively prescribed in the treatment of urolithiasis, as well as to control the recurrence of stone formation in the urinary tract.

The main active ingredients of the herbal preparation Trinefron are:

· Phenolic glycosides and phenolcarboxylic acids (rosemary, lovage and centaury) - antispasmodic and stimulating diuresis effects, acidification of urine;

· Phthalides (centaury) - antispasmodic effect;

· Secoiridoid bitterness (centaury) - a vasodilating effect;

· Essential oils - terpen (lovage, rosemary) - diuretic effect;

Flavonoids (centaury, rosemary) - anti-inflammatory, antibacterial, antioxidant effect.

The drug has a wide range of pharmacological effects, in particular, diuretic (diuretic), antispasmodic, anti-inflammatory, vasodilation, antimicrobial and nephroprotective.

A randomized, prospective study by Dudar et al. Showed a significant reduction in the incidence of episodes in individuals with recurrent cystopyelitis (an inflammatory disease of the bladder and urinary tract) who received a herbal preparation. The complex included the same centaury, rosemary, as well as lovage in similar Trinefron doses. The drug was taken as prophylaxis for 3 months after standard therapy compared to relapse prevention using herbal tea. In patients taking this herbal complex along with standard therapy, the cure rate was much higher compared to patients receiving only standard therapy (Kurt G. Naber, 2013).

When using any drug during pregnancy, safety and tolerability are always important. In 1762 pregnant women who received doses of a drug of a similar composition Trinefronno side effects have been reported. In addition, in two studies, the possible effect of this plant complex (a drug of similar composition) was studied. Trinefron) on embryogenesis and development of children after birth (Kurt G. Naber, 2013).

Nephroprotective effect of the drug (similar in composition Trinefron) was evaluated by the example of artificially reproduced Hayman glomerulonephritis in rats. Herbal medicine partially normalized the outflow of urine, accelerated glomerular filtration, slightly reduced the level of creatinine in the blood, and also significantly reduced the number of leukocytes in the urine. The combination of the plant complex with prednisone had a positive effect on the immune system and kidneys of rats.The complex effect of prednisolone and the plant complex was manifested in the rapid elimination of hematuria and the disappearance of leukocytes in the urine, a decrease in the level of metabolic products in the urine and cryoglobulins in the blood, as well as in an increase in the number of CD8 + cells (Sivak K.V. et al., 2017).

Trinefron It belongs to the group of drugs used in urology.

Composition and release forms

1. Drops for internal use Trinefron in bottles of tinted glass with a dispenser stopper, in a rectangular packaging made of cardboard there is one bottle. Each bottle contains 50 and 100 ml of the drug.

2. Trinefron in the form of capsules - dense gelatin capsules, have a light orange color. The capsules contain granules and brown powder.

Just ten units per blister, a cardboard package can contain either thirty capsules - three blister packs, or sixty capsules - six blister packs.

A drug Trinefron Is a herbal medicine with a combined composition.

Trinefron It has anti-inflammatory potential, produces a mild diuretic effect without disturbing the water-salt balance, stabilizes urine pH by acidifying it. Thus, adverse conditions are created for the multiplication of pathogenic microorganisms in the urine. It relaxes the smooth muscle fibers of the urinary tract, normalizing the outflow of urine, has an antibacterial effect. Thanks to the active chemical compounds contained in Trinefrone, the risk of stone formation is reduced.

Indications

1. Combined therapy of acute inflammatory processes of the urinary tract:

glomerulonephritis - inflammation of the glomerular apparatus of the kidney, and pyelonephritis - inflammation of the renal pelvis;

ureteritis - inflammation of the ureters of various etiologies;

cystitis is an inflammatory process in the wall or mucous membrane of the bladder.

2. Prevention of exacerbations in chronic inflammatory diseases of the urinary system.

3. Prevention of the appearance of stones with urolithiasis, including after extraction of calculi.

4. Prevention of secondary complications in congenital diseases of the urinary system.

5. Gestational pyelonephritis in pregnant women.

Dosage and administration

Drops

A single dose for adults, usually 50 drops Trinefron 3 r / day

· A single dose for children over 6 years old, usually 25 drops 3 r / day.

· A single dosage for children from 1 year to 5 years - 15 drops 3 r / day. After the course of treatment is completed, it is recommended to continue taking Trinefron as maintenance therapy (4-6 weeks) for the prevention of relapse.

· At reception Trinefron in drops, it is allowed to be diluted in milk, juice or another drink.

Capsules

Trinefron in capsules are swallowed without chewing, washed down with a small amount of liquid.

Adults - 2 capsules Trinefron 3 r / day

Children over 6 years old - 1 capsule of the drug 3 r / day.

Against the background of taking the drug, it is necessary to maintain water balance.

Adverse effects include dyspepsia: nausea, vomiting, diarrhea. A skin rash is rarely observed.

During clinical trials, the drug had no toxic effects.

Contraindications

1. Allergic reactions to the components of the drug.

2. Exacerbation of peptic ulcer of the stomach or duodenum.

3. The need for fluid restriction due to edema of renal etiology.

4. Lactose intolerance.

5. It should not be prescribed as a first-line drug for the treatment of edema.

findings

Trinefron - multicomponent preparation of complex action. With the right course in combination with heavy drinking, it eliminates the factors that cause the formation of stones in the urinary tract. Suitable for the treatment of diseases of the urinary system in pregnant women, this is a good alternative, since Trinefron does not show toxicity, and many antibiotics are contraindicated for pregnant women.

It is also worth noting the fact that the percentage of bacteria resistance to antibiotics is growing inexorably in the world, and Trinefron shows good results as therapy for asymptomatic bacteriuria without the use of antibacterial drugs.

Trinefron It is not indicated as the main therapy for acute glomerulonephritis and pyelonephritis, and is also not used as the drug of choice in the treatment of renal failure. Ineffective for eliminating already formed stones, but only as a background prevention of the formation of new calculi. Do not use the medicine as a diuretic.

This drug, belonging to the group of herbal medicines, is suitable for long-term background use, works to normalize the composition and quality of urine.

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