RU2592234C1 - Agent for preventing and treating phosphate nephrolithiasis - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to an agent for prevention and treatment of phosphate nephrolithiasis. Above agent represents an extract of herbal preparation, where the preparation includes 1-3 parts of pipsissewa, 1-2 parts of wood betony, 1-2 parts of European pyrola, 1-3 of calamus root, 2-4 parts of tormentil root, 1-2 parts of dandelion root, 1-3 parts of marjoram herb, 1-3 parts of common centauries, 2-4 parts of nettle leaves, and boiling water is used as extraction agent.

EFFECT: invention produces antibacterial effect upon urine, promotes calculus dissolution and removing out of kidneys, is characterised by absence of side reactions and toxic effect.

1 cl, 1 tbl, 3 ex

Description

The invention relates to pharmaceuticals, in particular to the creation of pharmacological agents of plant origin with nephrolytic action, which can be used for the prevention and treatment of urolithiasis (ICD).

The present invention is a continuation and development of previous works of the authors previously reflected in a number of patents, for example:

- RF patent No. 2205655 "Means for the prevention and treatment of urolithiasis" (Orlova SV, Chaban NG and others), 06/10/2003;

- RF patent No. 2238735 "Means for litholysis of urinary stones and a method for its production" (Chaban N.G., Belousova A.S. et al.), 10.27.2004;

- RF patent No. 2304425 "Method for determining the composition of urinary stones in vivo" (Kuzmicheva G.M., Chaban N.G. et al.), 08/20/2007.

The versatility of the action of herbal remedies makes herbal medicine an indispensable component of the complex treatment of ICD. Herbal medicine expands the possibilities of medicine for chronic inflammatory diseases of the genitourinary system, when long-term treatment is required, and the use of chemotherapeutic agents is not effective or desirable.

Currently, there are several dozen herbs used to treat IBD. Isolated use of herbs is rarely used, usually use fees. The advantage of using herbal preparations over synthetic preparations is the following:

- there are practically no complications and undesirable side effects;

- the scope for maneuvering is increased, which avoids addiction, which reduces the final result;

- the possibility of selecting such combinations of medicinal herbs that, on the one hand, mutually enhance individual properties, and on the other hand, provide the patient with all the necessary set of biologically active substances such as flavonoids, glycosides, alkaloids, essential oils, polyphenols, tannins, vitamins , bitterness, mucus, organic acids, coumarins, volatile, mineral salts, resins, oils, gums.

Phosphate stones contain salts of phosphoric acid. The most common of all phosphates are struvite MgNH ₄ PO ₄ × 6H ₂ O and carbonatapatite Ca ₁₀ (PO ₄ ) ₆ CO ₃ . The composition of phosphate stones may also include brushite CaHPO ₄ × H ₂ O, vitlokite β-Ca ₃ (PO ₄ ) ₂ ; phosphate infectious (secondary) stones may contain up to 15% hydroxylapatite - Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ . Phosphate stones look like powdery casts of white, light yellow, sometimes light brown. They have a smooth or slightly rough surface, a variety of shapes, including coral, and soft consistency. They are white or light gray in color, are formed in alkaline urine, are easily crushed [Tiktinsky OL, Alexandrov VP Series "Modern Medicine": Urolithiasis. SPb .: Piter Publishing House, 2000. - 384 pp.] A distinctive feature of phosphate stones is the high content of the organic matrix — up to 30%. Phosphate stones are radiopaque due to the presence of calcium in them: on the survey urograms, the outer borders of such stones are even, the contrast of the x-ray shadow in approximately half of the cases is uneven - layered or with focal enlightenments. The effectiveness of remote shock wave lithotripsy of phosphate stones is 80-90% with sizes up to 15 mm. Note that salts of the brushite type, which are relatively rare and in small amounts in stones, have no practical significance in terms of lithotripsy and conservative treatment [Neymark A.I., Neymark B.A., Kablova I.V. Urolithiasis disease. M .: Publishing house "GEOTAR-Media", 2011. - 218 p.]

The cause of the occurrence of phosphaturia and phosphate stone formation is the urease-forming infection of the groups proteus, pseudomonas, enterobacter, etc. in the form of monocultures or microbial associations. The urease urease produced by these microorganisms undergoes hydrolysis of urine urea to form the NH ₄ ⁺ ion in it. The latter alkalizes urine and forms a precipitate of phosphates. At the same time, these microorganisms in the process of their life release inflammatory products - hydrophobic colloids (mucus). Urine infection is observed with cystitis, pyelonephritis, in the presence of drainage systems in the urinary tract, endoscopic examinations and operations. In inflammatory processes, leukocytes, erythrocytes, necrotized urothelium and other components that increase the viscosity of urine and promote the conglomeration of phosphate salts accumulate in the urine [Kolpakov I.S. Urolithiasis disease. Academy Publishing Center, 2006. - 224 p .; Korsun V.F., Zakharov P.A., Korsun A.A. Family herbalist professor Korsun. M., 2009. 324 p.].

Phosphate stone formation occurs in two phases: initially (the first phase) free phosphates (phosphaturia) are formed directly in the urine, and then (the second phase) the formed phosphate crystals co-precipitate with organic substances, including those of inflammatory origin, and stone growth. If in this case free accompanying crystals of oxalates, uric acid or cystine are formed in the urine, they do not participate in the construction of the corresponding stones and are freely excreted by the urine. Phosphaturia and phosphate stone formation can have a double origin: 20% are various disorders of phosphorus-calcium metabolism, 80% are inflammatory processes in the organs of the urinary system [Levkovsky S.N. Urolithiasis: prognosis and metaphylaxis. St. Petersburg: Beresta Printing House LLC, 2010. - 120 p.] Due to the coprecipitation of salt phosphate components, phosphate urinary stones form either a layered or sedimentary structure, and the crystals in them are arranged randomly (isometrically), i.e. they are not oriented by their faces to the centers of growth of stones. Consequently, phosphaturia is a prerequisite for the growth of phosphate stones, and it occurs only during the presence of free crystals and amorphous phosphate compounds in the urine. It is also the main mechanism of alkalization of urine in metabolic phosphate urolithiasis.

Phosphates are excreted from the body by the intestines and kidneys. Normally, phosphorus is excreted in the urine in the form of sodium and calcium salts of phosphoric acid in the dissolved state - only when the urine is acidic.

For the treatment and relapse of stone formation, consisting of calcium and magnesium phosphates, acidification of urine is necessary. It contributes to the creation of adverse conditions for the life of bacteria and the dissolution of phosphate calculi. From conservative agents for the treatment of phosphate nephrolithiasis, it is necessary to use anti-inflammatory, diuretic, antispasmodic, antibacterial agents, as well as drugs that reduce the absorption of salts in the intestine and facilitate their excretion in the urine. Herbal preparations can:

- contribute to the formation of protective colloids of the urinary tract and the excitation of excretory function of the kidneys;

- reduce inflammatory processes;

- bind phenols;

- enhance the release of sodium ions and chloride ions of blood;

- neutralize microorganisms and products of their vital activity.

The prior art collection, consisting of the pods of common beans, motherwort leaves, femur roots (saxifrage), smooth hernia grass, shepherd’s bag grass [Kruglyak L. “Kidney stones”. SPb .: Publishing house "Peter", 2002. - 94 p.]. However, this collection is not always effective due to the weak diuretic effect. In addition, with prolonged use of this collection, a toxic effect is possible, since the leaves of the motherwort have cumulative properties.

Known collection of herbs and plant materials, which includes the fruits of anise, the fruits of parsley, the grass of the shepherd’s bag, the fruits of juniper ordinary, the root of the prickly steel, the root of the lovage drug, the root of the dandelion medicinal [Kruglyak L. “Kidney stones”. SPb .: Publishing house "Peter", 2002. - 94 p.]. However, this collection can cause side effects in the form of increased choleresis, which subsequently leads to attacks of cholecystitis, due to the relatively high content of anise fruits. The use of this collection can lead to the movement of calculi and, as a result, to pain syndrome, and in some cases to emergency surgery.

A collection is also known, which includes dioica nettle, rhizome of calamus swamp, peppermint leaf, field horsetail grass, black elderberry flowers, heart-shaped linden flowers, common juniper fruits, rosehip fruits [Tiktinsky OL, Aleksandrov V.P. Series "Modern Medicine": Urolithiasis. SPb .: Piter Publishing House, 2000. - 384 pp.] The use of this collection is not always accompanied by a clinical effect, due to the lack of a significant effect on diuresis, and normalization of the function of the urinary system.

Known drug "Kanefron" on the basis of plant materials, containing centaury grass, peel of rose hips, rosemary leaves and root of the lovage [VIDAL. Medicines of Russia. Section B. M .: Publishing house "AstraFarmService", 1999. - 270 p.]. The presence in Kanefron of flavonoid compounds, tannins, quinones and rosmarinic acid should contribute to the destruction of urinary stones and have a diuretic, anti-inflammatory, antimicrobial and antispasmodic effect. However, the drug has a narrowly targeted effect, and the effectiveness of the destruction of phosphate stones and anti-inflammatory activity of the drug are negligible.

The closest technical solution to the proposed invention is a collection consisting of 14 types of medicinal plant materials: spiky lavender grass, blackcurrant leaves, birch leaves, ivy buds, common juniper fruits, hop cones, lingonberry leaves, large plantain leaves, forest strawberry fruits, shoots of field horsetail, medicinal sweet clover grass, shepherd’s bag grass, blue cornflower flowers, ordinary flax seed [Kruglyak L. “Kidney stones”. SPb .: Publishing house "Peter", 2002. - 94 p.]. This fee has several disadvantages. The presence of strawberry fruits in the collection causes the risk of allergic rashes. Allergic reactions to lavender grass in the form of cough and runny nose are also possible. Plantain leaves in patients with high acidity can cause dyspeptic symptoms in the form of heaviness in the epigastric region, nausea and constipation. Ivy-shaped budra sometimes causes irritation of the kidneys, expressed in rapid urination and discomfort in the lumbar region and back. Since the medicinal raw materials are not crushed, there is no complete extraction of the active substances, and thereby the clinical effect is weakened. Thus, the collection in the prototype does not always lead to the achievement of the desired clinical effect.

The technical result of the claimed invention consists in enhancing the clinical effect of the proposed collection of medicinal herbs and obtaining a therapeutic effect, expressed in the antibacterial effect on urine, dissolution and excretion of calculi from the kidneys in the absence of adverse reactions and toxic effects.

The claimed technical result is achieved by the use of an extract of the collection of medicinal plant materials, which include components in the following ratio (in parts):

umbilical hobby - 1 ÷ 3;

initial letter medicinal - 1 ÷ 2;

round-leaf pear - 1 ÷ 2;

calamus marsh - 1 ÷ 3;

cinquefoil erect - 2 ÷ 4;

medicinal dandelion - 1 ÷ 2;

oregano - 1 ÷ 3;

centaury umbrella - 1 ÷ 3;

nettle - 2 ÷ 4.

A new and important factor for achieving a technical result is the presence of certain biologically active components — phenolcarboxylic acids, bioflavonoids, minerals, and vitamins in the plant material used in the composition of the proposed product.

The inventive tool in the form of an extract must be used within 3 weeks for 1 (one) tablespoon 2 times a day.

Umbrellas umbrella (grass)

Ingredients: glycosides (arbutin, homoarbutin, andromedotoxin), flavonoids (kempferol), tannins (5%), bitterness, gallic acid, gum, salicylic acid methyl ester, resinous substances.

Properties: diuretic, bactericidal.

Initial letter medicinal (grass)

Ingredients: essential oil, flavonic glycosides, vitamins C and K, alkaloids (concretein, stachydrin), tannins, bitterness, calcium salts.

Properties: diuretic, choleretic, bactericidal, improves metabolism.

Grushanka round-leaved (grass)

Ingredients: triterpenoids (oleanic, ursolic, betulinic acids), flavonoids (kempferol, quercetin, hyperoside), glycosides (saponins, dolphinidin), coumarin, citric, malic, oxalic acid, carotene, vitamins C, K, P, active component - group cyclopentanpyran monoterpenoids.

Properties: bactericidal, diuretic, anti-inflammatory.

Calamus marsh (roots)

Composition: bicyclic monoterpenes and their oxygen derivatives, cyclic sesquiterpenes and their oxygen derivatives, ketones, phenols and phenyl ethers, bitter glycoside acorin, ascorbic acid, tannins.

Properties: diuretic, choleretic, anti-inflammatory.

The cinquefoil is erect (roots)

Composition: ellagic and quinic acids, tannins with a predominance of condensed tannins.

Properties: anti-inflammatory, diuretic, antimicrobial; destroys urinary stones, interacting with the inorganic and organic components of the stone.

Medicinal dandelion (roots)

Ingredients: saponins, triterpene alcohols, protein, bitterness, vitamins A ₁ , B ₂ , C, PP, tannins, resins, fatty oil, mucus, sucrose.

Properties: diuretics, laxatives, loosens and dissolves stones, lowers urine pH.

Oregano (grass)

Ingredients: phenols (thymol), geranyl acetate, tannins and pigment substances, fatty oil, essential oil, vitamins A, D, E, K, C, B1, B2, B5, B6, B9.

Properties: diuretic, antimicrobial, can be used for infectious diseases of the genitourinary system.

Centaury umbrella (grass)

Composition: phenolcarboxylic acids in free (o-hydroxyphenylacetic) and in a bound state (n-coumaric acid predominates), essential oil, resin, mucus, wax, terpenes, triterpenes, flavonoids, flavonic glycosides, vitamins C and PP, pharmacological activity determines iridoid glycosides are bitterness.

Properties: antibacterial, anthelmintic, laxative, helps to increase the secretion of digestive glands and increase bile secretion.

Nettle (leaves)

Ingredients: vitamins K, C, B2, pantothenic acid; carotenoids, β-carotene, xanthophyll, urticin, tannins, formic acid, mineral salts, riboflavin, phytosterone, histamine.

Properties: diuretic, anti-inflammatory, normalizes metabolism.

To obtain the claimed drug, all types of medicinal raw materials were crushed, mixed in certain proportions, brewed with boiling water and insisted in a thermos for 6-8 hours. The extracts were separated by filtration and then used to carry out litholysis of stones extracted from patients with ICD. Note that stones of various compositions were obtained during surgical treatment of 56 patients.

Litholysis was carried out as follows: the stone was placed in a plant extract, kept for two weeks at room temperature, filtered, the precipitate was dried in an oven to constant weight, and then weighed. Litholysis time is 3 weeks.

The density of urinary stones (in relative units of H) was determined in vivo by spiral X-ray computed tomography on a General Electric instrument. Further, using the density equation calculated from x-ray data (ρ, g / cm ³ ) and found by tomography, N,

ρ = 1.539 + 0.000485 N,

the composition of urinary stones was determined [Alyaev Yu.G., Belousov S.R., Bukin V.I., Kuzmicheva G.M., Rapoport L.M., Rudenko V.I., Chaban N.G. Integrated study of urinary stones // Zh. non-organ. Chem. - 2002.V. 47, No. 3. S. 456-464].

Measurements of the pH of the solutions were carried out using a universal pH meter pH-340 Ekoniks Expert.

The invention is illustrated by the following examples.

Example 1

The composition of the claimed funds when containing the ingredients in parts:

umbilical umbrella - 1;

initial letter - 1;

round-leaved pear - 1;

calamus marsh - 1;

cinquefoil erect - 2;

medicinal dandelion - 1;

oregano - 1;

centaury umbrella - 1;

nettle - 2.

Example 2

The composition of the claimed funds when containing the ingredients in parts:

umbilical umbrella - 3;

initial letter medicinal - 2;

round-leaved pear - 2;

calamus marsh - 3;

cinquefoil erect - 4;

medicinal dandelion - 2;

oregano - 3;

centaury umbrella - 3;

nettle - 4.

Example 3

The composition of the claimed funds when containing the ingredients in parts:

umbilical umbrella - 2;

initial letter - 1;

round-leaved pear - 2;

calamus marsh - 2;

cinquefoil erect - 3;

medicinal dandelion - 2;

oregano - 2;

centaury umbrella - 2;

nettle - 3.

In all the above examples, extracts were obtained by pouring mixtures of medicinal plant materials with boiling water.

The results of in vitro litholysis of phosphate stones of various compositions are presented in table 1. Obviously, the most durable phosphate stones are apatites Ca ₁₀ (PO ₄ ) ₆ CO ₃ and Ca ₁₀ (P0 ₄ ) ₆ (OH) ₂ .

Studies on litholysis of phosphate stones in vivo. It was found that taking the proposed drug in patients with phosphate stones contributed to a decrease in urine pH from 7.5-7.0 to values of 4.3-4.6 within 10 days and the disappearance of urease-forming infection in the urine. It is shown that, compared with similar in vitro experiments in water, in vivo dissolution of phosphate stones proceeds faster. These fees were tested on 14 patients with phosphate nephrolithiasis at the Department of Urology 1 MGMU them. THEM. Sechenov and demonstrated a pronounced therapeutic effect superior to the action of known analogues.

All medicinal plants used in the composition of the proposed product are of domestic origin, are included in the Pharmacopoeia of the Russian Federation (and earlier - the USSR) from the 1st to the 11th editions, are known in medical practice and are widely used in herbal medicine for various purposes.

Claims (1)

Means for the prevention and treatment of phosphate nephrolithiasis based on the extract of the collection from medicinal plant materials, characterized in that the collection includes components in the following ratio, in parts:
umbrellas grass 1-3 herb initial letters 1-2 pear grass 1-2 calamus roots 1-3 uproot roots 2-4 dandelion roots 1-2 oregano grass 1-3 umbrella centaury grass 1-3 nettle leaves 2-4,
and boiling water is used as an extractant.