Medication with nephroprotective action and method of obtaining thereof

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the pharmaceutical industry, in particular to a medication, possessing a nephroprotective action. The medication with the nephroprotective action, contains an extract of grass with roots and rhizomes of slender-leaf iris (Iris tenuifolia), stabilising agents and preservatives, taken in a certain ratio, where the extract is obtained by extraction of the grass with roots and rhizomes of slender-leaf iris (Iris tenuifolia) with a 30-70% water solution of polyol.

EFFECT: medication possesses an effective nephroprotective action.

3 cl, 3 dwg, 7 tbl, 14 ex.

 

The technical field to which the invention relates.

The invention relates to the pharmaceutical industry, in particular to the development of new effective herbal remedies nephroprotective actions.

The level of technology

Currently, the number of patients with nevropatologii is growing rapidly. However, in medicine, virtually no drugs, can have a therapeutic pathogenetic impact of these diseases. In particular, this applies to glomerulonephritis, in which the treatment is to try to slow down the pathological process through the use of immunosuppressants, and in the end almost always this disease is fatal. Of great importance in the treatment of kidney patients herbs commonly used in aqueous decoctions and infusions, often in the form of alcoholic extracts. A decoction of the leaves of bearberry or cranberry has an antimicrobial effect on the microflora of the urinary tract due arbutin, mild antispasmodic effect and successfully used for pyelonephritis and kidney stones. A decoction of horsetail, Java staminate, flowers, cornflower blue, birch buds stimulate the secretion of urine (diuretic effect) that has therapeutic value for edema of renal origin. Lisinopril (liquid e is strict lespedeza capitate) and flaronin (preparation of Astragalus serpophaga) increased diuresis and thus stimulate nitrogen-emission kidney function, that allows to use them in complex therapeutic agents in chronic renal failure. A number of herbal remedies is effective in the treatment of kidney stones - canephron, ciston, drugs madder, spore and others. However, available in the Arsenal of medicine drugs have mainly symptomatic action, not stopping the development of the pathological process. Therefore great importance is the development of drugs capable of exerting a therapeutic effect on the disease process in parenchyma kidney, particularly in the development of glomerulonephritis is the most severe and the most resistant to treatment, and disease.

In medicine of Mongolia and Tibet to treat diseases of the kidneys used infusions widely known fine leaved iris (Iris teniufolia) grown in the South Gobi regions of Mongolia. LLC "Monos Pharma, Mongolia (manufacturer LLC PharmaMed", Russia) offers on the market of alcoholic extract of iris fine leaved (http://www.farmamedspb.ru/component/content/article/21-bad.html as nephroprotective funds. In addition, veterinary drug "Photodoc-nephrops" offered Agrovetzaschita" as a nephroprotective agent, as active substance contains purified alcoholic extract of the underground part of the fine leaved iris (Iris tenuifolia) ( id=370)

Ledue is to be noted, what is known the use of drugs of various kinds of dear for all sorts of reasons, for example: to reduce or relieve tension on the skin and/or subcutaneous tissue (W0 97/35556, 1997.10.02, EN 98119466, publ. 27.08.2000), to stimulate bone growth (2004121173, publ. 10.01.2006), for the biological purification of water from salts (EN 2094392, publ. 27.10.1997), as burns funds (RU 2195307, publ. 27.12.2002), for weight management and prevention of obesity in Pets (EN 2313228, publ. 27.12.2007), in Oncology practice (Yakovlev, P., Blinov, K. F. Botanical-pharmacognostically dictionary. - M.: Higher school, 1990, S. 192.), a face and painkillers (Evans W. C. Trease aand Evans. Pharmacognosy. 14-th Edition. London, 1996, c.327 and 476). In addition, the complex proposed in EN 2123349, publ. 20.12.1998 with anti-inflammatory, immunomodulatory and antihypoxic effect, representing the dry extract of my milky white (Iris lactea Pallas). On its basis have been proposed various dosage forms: tablets, lozenges, syrups... (EN 2140277, publ. 27.10.1999). In (Diss. Kida. Biol. Sciences Sivak K. C. Pharmacological study of some vegetable nephroprotection (experimental study), St. Petersburg, 2007) it was noted that the dry extract of my milky white is promising for the creation of nephroprotective drugs on istia and for clinical studies.

However, the above-described dosage forms and liquid and dry extracts - require the use of large quantities of food alcohol, which leads to well-known economic costs and logistical challenges, the procedure is not cost effective. Storage, transportation and sale of formulations containing alcohol, is also associated with great difficulties. [EN 2140277 publ. 27.10.1999] proposed a syrup containing 62-66% of sugar, the production of which is of the dry extract of my milky white, used as an immunomodulator. Although this solves a number of problems related to logistics (because the product does not contain high concentrations of ethanol, not the fire), but this form has several disadvantages:

- to dissolve the extract of the authors, along with the sugar syrup, add ethanol;

himself dry extract produced by extraction with ethanol and subsequent distillation of the solvent;

sugar makes it impossible for the standardization of the drug polysaccharides, which are considered to be the component most responsible for therapeutic effects of herbal remedies.

Thus, the aim of the invention was to solve two problems:

- development of phytomedicine with marked nephroprotective effect and, in particular, suitable for the treatment of glomerulonephritis;

- complete elimination of COI is whether food alcohol from the process.

Disclosure of inventions

The invention is realized by the fact that the proposed drug with the nephroprotective effect, represents an extract of the herb with roots and rhizomes of fine leaved iris [Iris tenuifolia] in an aqueous solution of a polyhydric alcohol containing stabilizers and preservatives.

Unexpected was that the extraction of dry grass with roots and rhizomes of fine leaved iris [Iris tenuifolia] 30-70% th aqueous solution at a weight ratio of extractant: dry grass rhizome =(4÷5):1) such polyhydric alcohols as 1,2-propylene glycol and/or glycerol and/or sorbitol and/or xylitol and others, is more efficient than extraction 30-70% ethanol. The extract is transferred and polysaccharides, presumably largely determine the main effects of the drug, while extraction with concentrated ethanol solutions of practically they are not extracts (see table 1).

Table 1
Comparison of alcohol Netrokona and sorbitol
No. series Netrokona-syrupKey indicators
The total content of flavonoids in PE is eschete on apigenin, mg/mlThe content of polyphenols in terms of Gallic acid (mg/mlThe content of polysaccharides (mg/mlThe total content of iridoids, mg/mlPHDensity, g/cm3The dry residue, %
N(C)L1,6the 4.757,40,55,01,041,4
N(C)L2,35,963,11,25,01,052,6
N(C)L0,82,965,60,6a 4.91,030,8
N(C)L1,14,075,90,4the 4.71,03 1,2
Afroman-spirit0,20,7the 4.70,5-0,970,2

Since aqueous solutions of polyhydric alcohols have a high viscosity, has proved to be expedient to carry out the extraction at moderately elevated temperatures (60-90°C; at temperatures below 60°C. the solution is too viscous and is retained by the meal at a temperature above 90°With the possible destruction of the components (glycosides, flavonoids and xanthones) extract. The study of the kinetics of extraction showed that under these conditions the equilibrium concentration of indicator components (flavonoids, polysaccharides, iridoids) installed through 4-7,5 hours depending on temperature and extractant, while using as extractant 50% ethanol at room temperature, the equilibrium concentration of indicator components are installed in 3 days.

In the extract can be used as stabilizers ascorbic acid concentration (0.1 to 1.0)%, which is an antioxidant and supports a pH in the region of maximum chemical stability phytoextract (from 3.5 to 5.0), and as preservatives benzoic acid is or its pharmaceutically acceptable salt concentrations (0.01 to 0.5)% and/or sorbic acid or its pharmaceutically acceptable salt concentrations (0.01 to 0.6)%. When the concentration of the preservatives is less than 0.01% of the drug is not withstand the stated shelf life (2 years) for microbiological purity. At the same time to use preservatives in amounts larger than reported (for benzoic acid and its salts and 0.5% sorbic acid and its salts - 0,6%), inappropriate. Proposed as bacteriostatic-stabilizers for "syrup" esters of p-oksibenzoynoy acid (parabens) can also be used, but less acceptable in view of the known side effects.

Thus obtained syrups stable during storage (example 1, 2, 6, 7), they have a strong and reliable effect in the treatment of renal pathology, and therapeutic effect is much greater than the effect known nephroprotective drug - "Lesperon" (example 14).

Highly active extracts with nephroprotective effect can be obtained in a single extraction grass with roots and rhizomes of fine leaved iris (Iris tenuifolia) aqueous solutions of polyhydric alcohols with the above concentrations and in specified conditions. However, in this case a significant amount of the extract is retained by the meal and lost: up to 600-700 g with load dry grass 500, To avoid loss of extractives, increasing the degree of extraction, reduce wasteful rubbed the polyhydric alcohol extraction is advantageously carried out in three stages. Each portion grass of fine leaved iris with rhizome extracted three times, with the extractant for dry herbs is prepared by mixing a polyhydric alcohol and the extract obtained in the second extraction, the extractant for the second extraction using the extract obtained in the final third extraction, and as an extractant for the third extraction using water.

While in the meal virtually no valuable extractives and no loss polyhydric alcohol. Thus, the proposed method of producing a medicinal product allows to extract from the meal biologically active substances with minimal loss of valuable components.

To reduce the degradation of glycosides, flavanoids and xanthones thermal effects in the extraction process, and also to eliminate the growth of microorganisms in the wet cake (between the first and second; second and third extraction), stabilizers and preservatives suitable to be loaded into the extractant for dry grass. If the concentration of ascorbic acid or preservatives in the product is less than the lower limit (for ascorbic acid and 0.1%, for preservatives - 0,01%), the estimated number of required components add to the final syrup.

The amount of polyhydric alcohol, taken in the preparation of EXT the agent for dry grass, is in a weight ratio to the dry grass (1,2÷2,8):1, and the quantity of water taken for the final third extraction, is in a weight ratio to the dry grass(1,2÷3):1.

The resulting syrup was tested for pharmacological (nephroprotective) activity was determined by its acute and chronic toxicity, a study of its allergenicity and immunotoxicity, embryotoxicity, mutagenic and carcinogenic actions, effects on reproductive function (report on experimental pre-clinical study of the safety and pharmacological activity of the drug "Afroman syrup for oral administration" production LLC PharmaMed", EKATERINBURG it FMBA of Russia, Saint-Petersburg, 2012) from the calculation of its use 5-10 ml 3 times a day. In the result of the study drug "Afroman syrup for oral administration" was recommended for clinical trials in chronic kidney disease as a low-toxic and effective medicines.

The results of studies of acute toxicity and toxicometric drug "Afroman syrup for oral administration" (see example 12) can take it to the V class is practically non-toxic drugs (N. Hodge et al. Clinical Toxicology of Commercial Products. Acute Poisoning. Ed. IV, Baltimore, 1975, 427 p.) and low-hazard substances (IV hazard class according to GOST 12.1.007-76).

According to the results of the research the subacute and chronic toxicity "Afroman syrup for oral administration (see example 13) using it after intragastric administration once a day for 90 days at doses of 500, 5000 and 10000 mg/kg in rats of both sexes does not cause changes in appearance, General condition and behavior of animals, not have a negative impact on biochemical blood parameters and basic physiological functions of the body, does not cause pathological changes, which indicates a good tolerability and safety dosage form of the drug.

Developed the drug to allow effective treatment of severe, considered to be almost incurable kidney disease with fatal chronic glomerulonephritis, is restored as the excretory function of the kidneys, normalized and immune factors with attenuation of autoimmune destruction of the structure of the kidney (example 14). The proposed method of treatment of chronic glomerulonephritis is long, up to the normalization of renal function, pills introduction developed drug, the optimal dose and regimen three times a day for 5-10 ml of the extract. The proposed method of treatment may be used as monotherapy, and be accompanied by the use of other therapeutic agents antibiotics, immunomodulators, etc. for use with the tet necessary by the attending physician.

Brief description of drawings

Fig.1. Fatty degeneration neuroepithelial convoluted tubule of the kidney poisoned rats. Color Sudan. Magnification 40×7.

Fig.2. Proteinases neuroepithelial proximal tubules of the cortical substance of the kidney poisoned rats. The indistinguishability of cell borders, pikes cores, desquamated cells in the lumen of the tubules. Paint hematoxylin-eosin. Magnification 40×7.

Fig.3. Nearly normal structure of the cortical substance of the kidney poisoned rats after treatment Netrokona syrup for oral administration". Paint hematoxylin-eosin. Magnification 40×7.

The implementation of the invention

Example 1 (sorbitol, 90°C, three stage extraction)

The first extraction

In a glass reactor placed 500 g of grass (with minor compaction) with roots and rhizomes of iris fine leaved.

In a glass beaker with a volume of 2 l put the extract obtained in the second extraction previous boot, heated to 30°C and under stirring with a glass rod make 1 kg of sorbitol; when the temperature of the glass extractant warm up. After complete dissolution of sorbitol in a glass, add 10 g Pharmacopoeia of ascorbic acid and 5 g of potassium sorbate; stir until dissolved and loaded into the reactor with grass. Heat the contents of the reactor to 90°C and kept at this temperature is; after 3 hours of exposure determine the total content of flavonoids in the extract of SF-method (photomatrixovina in the form of an aluminum complex), the analysis should be repeated after 1 hour; the coincidence of the results of the analysis of the extraction process completes, by increasing the concentration of flavonoids lengthen the shutter speed to 1 hour and re-define the content of flavonoids.

After extraction of the hot extract is drained (by gravity) on a glass funnel and filtered. Get 1250 g dark brown filtrate with a pleasant characteristic odor of extract of the herb with roots and rhizomes of iris fine leaved. Extract parameters as follows:

- pH 4.5

the density of 1.26 g/cm3(at 20°C)

- total content of flavonoids in terms of apigenin (UV spectrophotometry) 1.9 mg/ml

the content of polyphenols in terms of Gallic acid 5.0 mg/ml

the content of polysaccharides 77.0 mg/ml

- the content of iridoids in terms of harpagide acetate 1.1 mg/ml

- microbiological purity:

- total number of aerobic bacteria in 1 g of 1.0×103(norm is not more than 104)

- the total number of fungi in 1 g absent

- E. coli in 1 g absent

- Salmonella in 10g - no

- Enterobacteriaceae in 1 year or less 10 (norm - not more than 102)

- St. Aureus in 1 g absent

The second extraction

The meal in the reactor poured ek is a path, obtained by the third extraction previous boot, heated to 90°C and maintained until the establishment of the equilibrium concentration of indicator components (amount of flavonoids) in the liquid phase, and then filtered. The extract is # 2, which is used for preparation of the extractant on the first extraction load it later.

The third extraction

By remaining in the reactor feeds poured 1500 ml of purified water, incubated at 90°C before the establishment of the equilibrium concentration of indicator components (amount of flavonoids) in the liquid phase and filtered. Obtained in this extract No. 1 is used for the second extraction can be loaded later. Get 1358 g of wet cake (65,5% moisture), practically does not contain detectable quantities of flavonoids, polysaccharides, iridoid.

After two years of storage parameters of the obtained extract of the herb with roots and rhizomes of iris fine leaved the following:

- pH 4,48 - density 1.22 g/cm3(at 20°C)

- total content of flavonoids in terms of apigenin 1.6 mg/ml

the content of polyphenols in terms of Gallic acid 4.5 mg/ml

the content of polysaccharides 73,0 mg/ml

- the content of iridoids 0.9 mg/ml

- microbiological purity:

- total number of aerobic bacteria in 1 g of 1.6×103(norm is not more than 104)

- the total number of fungi in 1 g - no longer is t

- E. coli in 1 g absent

- Salmonella in 10g - no

- Enterobacteriaceae in 1 year or less 10 (norm - not more than 102)

- St. Aureus in 1 g absent

Thus, the resulting syrup is an extract of the herb with roots and rhizomes of fine leaved iris (Iris teniufolia), stable in storage for 2 years.

Example 2 (single-stage extraction, 90°C, 50% sorbitol)

In a glass reactor with a volume of 2000 ml was placed 500 g of grass with roots and rhizomes of fine leaved iris (Iris teniufolia). Separately in a glass beaker, dissolve 1 kg of sorbitol in 1 l of water with stirring and heated to 30-40°C (sorbitol is dissolved with a significant temperature drop). In a warm solution of sorbitol add 5 g of potassium sorbate and 10 g of ascorbic acid pharmacopoeial quality. The resulting solution was poured into the reactor, the mass is heated to 90°C and maintained at this temperature and after 3 hours of exposure determine the total content of flavonoids in the extract of SF-method (photomatrixovina in the form of an aluminum complex), the analysis should be repeated after 1 hour; the coincidence of the results of the analysis of the extraction process completes, by increasing the concentration of flavonoids lengthen the shutter speed to 1 hour and re-define the content of flavonoids.

The solution is gravity discharged from the reactor on a glass funnel, filtered under vacuum. Receive 765 g of a dark-coric is avago extract of the herb with roots and rhizomes of iris fine leaved with the following options:

- dark brown syrup with a little rainy, muddy, has a characteristic pleasant smell

- pH 4,6

the density of 1.12 g/cm3

- total content of flavonoids in terms of apigenin 1.7 mg/ml

the content of polysaccharides 65.9 mg/ml

- the content of iridoids 1.0 mg/ml

the polyphenol content of 3.5 mg/ml

- microbiological purity:

- total number of aerobic bacteria in 1 g of 1.5×103(norm is not more than 104)

- the total number of fungi in 1 year or less 10 (norm not exceeding 102)

- E. coli in 1 g absent

- Salmonella in 10g - no

- Enterobacteriaceae in 1 year or less 10 (norm - not more than 102)

- St. Aureus in 1 g absent

After two years of storage options "product" as follows:

- dark transparent brown syrup with a film of sediment on the bottom, has a characteristic pleasant smell

- pH - 4,5

the density of 1.09 g/cm3

- total content of flavonoids in terms of apigenin 1,68 mg/ml

the content of polysaccharides 64,0 mg/ml

- the content of iridoids 0.9 mg/ml

the polyphenol content of 3.45 mg/ml

- microbiological purity:

- total number of aerobic bacteria in 1 g of 1.8×103(norm is not more than 104)

- the total number of fungi in 1 g absent

- E. coli in 1 g absent

- Salmonella in 10g - no

- Enterobacteriaceae in 1 year or less 10 (norm - not more than 102)

- St Aureus in 1 g - no

Thus, the resulting syrup extract of fine leaved iris (Iris teniufolia), stable in storage for 2 years.

Example 3 (sorbitol, 60°C)

The first extraction

In a glass reactor placed in a bath thermostat, placed 500 g of grass with roots and rhizomes of fine leaved iris (Iris teniufolia). A 2-liter beaker placed extract obtained in the second extraction the previous load, number 1470 (1210 ml) and 1000 g of sorbitol food; the contents of the glass slowly heated to 40°C. under stirring, the amount of mass 1960 ml beaker add 5 g of potassium sorbate and 10 g of ascorbic acid, is stirred until dissolution. The obtained dark brown syrup is poured into the reactor. The reactor is heated to 60°C and maintained until reaching the equilibrium concentration of indicator components (flavonoids) in the liquid phase, the extraction process takes up to 6.0 hours. Then the hot solution was poured onto a glass filter with a porous plate, filtered and receive 1320 g of the solution a dark brown color with a characteristic pleasant smell - an extract of the herb with roots and rhizomes of iris fine leaved ("product").

The second extraction

The meal in the reactor poured the extract obtained in the third extraction the previous load; the amount of this extract 1620 Meal in the reactor to extract heat is 60°C and maintained at this temperature to achieve equilibrium concentration of indicator components (flavonoids) in the liquid phase; then decant the extract by gravity into the funnel and filtered. Get 1470 g of extract No. 2, which is used for preparation of the extractant on the first extraction next boot.

The third extraction

The meal in the reactor add 1500 ml of distilled water, heated to 60°C in bulk and kept at this temperature to achieve equilibrium concentration of indicator components (flavonoids) in the liquid phase, and then filtered as described above. Get 1620 extract No. 1, which is used for the second extraction can be loaded later.

The amount of wet cake 1520 g; after drying to constant weight the amount of dry meal 486 g; extraction with 70% ethanol and dry meal and subsequent analysis of the extract indicates that there is virtually no end to the meal extractives.

Extract parameters of grass with roots and rhizomes of iris fine leaved ("product") at the time of packing the following:

- dark brown slightly turbid, foaming syrup with a characteristic pleasant smell

- pH - 4,51

the density of 1.28 g/cm3

- total content of flavonoids in terms of apigenin 2.0 mg/ml

- the content of iridoids 1.2 mg/ml

the content of polysaccharides 72,0 mg/ml

the polyphenol content of 3.5 mg/ml

After two years of storage under natural conditions:

- about is this at all a dark brown, foaming syrup with a characteristic pleasant smell

- pH - 4,51

the density of 1.23 g/cm3

- total content of flavonoids in terms of apigenin 1.8 mg/ml

- the content of iridoids 1.1 mg/ml

the content of polysaccharides 70.0 mg/ml

the polyphenol content of 3.46 mg/ml

Example 4 (xylitol, 60°C)

The process is conducted according to example 3, but as a polyhydric alcohol use xylitol in the amount of 1 kg. Get 1411 g of the extract with the following options:

- dark brown hazy, bubbly syrup with a pleasant characteristic odor

- pH of 4.4

- density of 1.24 g/cm3

- total content of flavonoids in terms of apigenin 1.4 mg/ml

- the content of iridoids 1.6 mg/ml

the content of polysaccharides to 57.0 mg/ml

the polyphenol content of 7.1 mg/ml

- microbiological purity:

- total number of aerobic bacteria in 1 ml of 6×102(norm is not more than 104)

- the total number of fungi in 1 ml or less 10 (norm not exceeding 102)

- E. coli in 1 ml - missing

- Salmonella in 10 ml no

- Enterobacteriaceae in 1 ml or less 10 (norm - not more than 102)

- St. Aureus in 1 ml - missing

Example 5 (1,2-propylene glycol, 60°C)

The process is conducted according to example 3, but as a polyhydric alcohol use 1,2-propylene glycol in the amount of 1 kg. Get 1502 extract with the following options:

those who but brown hazy, bubbly syrup with a pleasant characteristic odor

- pH of 4.9

- density of 1.1 g/cm3

- total content of flavonoids in terms of apigenin 3.0 mg/ml

- the content of iridoids 0.8 mg/ml

the content of polysaccharides 82,0 mg/ml

the polyphenol content of 6.1 mg/ml

- microbiological purity:

- total number of aerobic bacteria in 1 ml of 2×103(norm is not more than 104)

- the total number of fungi in 1 ml or less 10 (norm not exceeding 102)

- E. coli in 1 ml - missing

- Salmonella in 10 ml no

- Enterobacteriaceae in 1 ml or less 10 (norm - not more than 102)

- St. Aureus in 1 ml - missing

Example 6 (glycerin)

In a glass reactor with a volume of 2000 ml was placed 500 g of grass with roots and rhizomes of iris fine leaved. Separately in a glass beaker placed 1400 g of dry glycerol (H. H.), add 20 g of ascorbic acid, 12 g of potassium sorbate and 10 g of sodium benzoate, then add water up to 2 kg and stirred with a magnetic stirrer until complete dissolution of the components. The resulting solution is poured grass in the reactor, the mass is heated by thermostat up to 80±5°C and maintained, periodically determining the total content of flavonoids (SF-method) to establish their equilibrium concentration; the extraction process takes 7.5 hours. The solution is gravity drained from the reactor on a glass funnel, filtered under vacuum. Receive 954 g murky orange Siro is a - extract of the herb with roots and rhizomes of iris fine leaved, with a characteristic pleasant odor, with a small light sediment.

Extract parameters as follows:

- the density of 1.19 g/cm3

- pH of 4.7

the content of flavonoids in terms of apigenin 1.9 mg/ml

the content of polyphenols in terms of Gallic acid 9.0 mg/ml

the content of polysaccharides to 58.2 mg/ml

- the content of iridoids 1.2 mg/ml

After two years storage:

- slightly turbid, brown, foamy syrup with a pleasant characteristic (fruity) odor, sweetish-bitter taste, with a small light sediment

- the density of 1.19 g/cm3

- pH 4,6

the content of flavonoids in terms of apigenin 1.8 mg/ml

the content of polyphenols in terms of Gallic acid 8.5 mg/ml

the content of polysaccharides of 57.8 mg/ml

- the content of iridoids 1.0 mg/ml

Example 7 (xylitol, 1,2-propylene glycol, pH 3.5)

In a glass reactor with a volume of 2000 ml was placed 500 g of grass with roots and rhizomes of iris fine leaved. Separately in a glass beaker placed 670 g of xylitol, 670 g of 1,2-propylene glycol, add 2 g of ascorbic acid and water up to 2 kg; the mass is stirred until complete dissolution of the components. Because dissolution is accompanied by a decrease in solution temperature, the glass is heated in a water bath. The resulting solution is poured grass in reacto is e, the mass is heated by thermostat up (80±5)°C and maintained, periodically determining the total content of flavonoids, before the termination of the growth of their concentration in the liquid phase, the extraction process takes 7.5 hours. The solution is gravity drained from the reactor on a glass funnel, filtered under vacuum. Get 1015 g light brown extract with a characteristic pleasant odor of extract of the herb with roots and rhizomes of iris fine leaved. To the syrup to the filtrate add 0.2 g of sorbic acid and 0.2 g of benzoic acid, is stirred with a glass rod, and the intensity of the color of the extract is reduced.

Extract parameters as follows:

the density of 1.21 g/cm3

- pH - 3,5

the content of flavonoids in terms of apigenin 2.1 mg/ml

the content of polyphenols in terms of Gallic acid 5.4 mg/ml

the content of polysaccharides of 63.7 mg/ml

- the content of iridoids 0.4 mg/ml

After two years of storage of the sample extract in normal conditions:

- light brown transparent syrup with a pleasant smell, a bitter-sweet taste, with a slight dark sediment

the density of 1.21 g/cm3

- pH 3.5

the content of flavonoids in terms of apigenin was 2.05 mg/ml

the content of polyphenols in terms of Gallic acid 5.2 mg/ml

the content of polysaccharides of 63.5 mg/ml

- the content of IR is of Dodov 0.4 mg/ml

- microbiological purity:

- total number of aerobic bacteria in 1 g of 1.4×103(norm is not more than 104) SOME

- the total number of fungi in 1 g less than 10 CFU

- Salmonella in 10g - no

- enterobacteria in 1 g absent

- St.Aureus in 1 g absent

Thus, the concentration of stabilizer is ascorbic acid 0.1% preservative sorbic acid 0.01%, sufficient to stabilize the product.

Example 8 (70% 1,2-propylene glycol, 70°C)

In a glass beaker equipped with a magnetic stirrer, mix 700 g 1 2-propylene glycol, 5 g of ascorbic acid and 2.5 g of sorbate sodium, water is added to 1 kg and stirred until complete dissolution of the components.

In another beaker was placed 100 g of grass with roots and rhizomes of iris fine leaved, add 400 g cooked extractant and incubated in a water bath at 70°C before the termination of the growth in the concentration of flavonoids in the liquid phase, it takes 6.5 hours. The hot solution is drained, filtered. Get 274 g of the extract of the herb with roots and rhizomes of iris fine leaved with a characteristic pleasant odor, bitter taste, with the following options:

- density at 20°C 1.04 g/cm3

- pH - 5,0

- total content of flavonoids in terms of apigenin and 2.3 mg/ml

the content of polyphenols in terms of Gallic acid 5,7 mg/ml

content on the Ikharev 69,1 mg/ml

- the content of iridoids 1.2 mg/ml

Example 9 (30% 1,2-propylene glycol, 70°C)

The experience carried out analogously to example 8, but for the preparation of the extractant used 300 g of 1,2-propylene glycol and 4 g of ascorbic acid, 2.0 g of potassium benzoate and water up to 1 kg For the extraction of 100 g of grass with roots and rhizomes take 400 g cooked extractant. As a result of extraction get 236 g of a dark brown extract with a characteristic pleasant odor, with the following parameters:

- density at 20°C 1,03 g/cm3

- pH of 4.7

the content of flavonoids in terms of apigenin 1.1 mg/ml

the content of polyphenols in terms of Gallic acid 4.0 mg/ml

the content of polysaccharides 59,7 mg/ml

- the content of iridoids 0.4 mg/ml

Example 10 (Comparative experiment)

The experience is conducted according to example 2, but as extractant using 70% ethyl alcohol, stabilizers and preservatives are not added. The extraction is carried out at 20-25°C before the termination of the growth in the concentration of flavonoids in the liquid phase, the process lasts for 3.5 days. The liquid phase is drained and filtered. Get 1315 g of alcoholic extract is dark brown, with the following parameters:

- density at 20°C 0.97 g/cm3

the content of flavonoids in terms of apigenin 0.2 mg/ml

the content of polyphenols in terms of Gallic acid 0.7 mg/ml

- the content is of polysaccharides of 4.7 mg/ml

- the content of iridoids 0.5 mg/ml

Thus, ethanol is significantly less effective extractant than polyhydric alcohols.

Example 11 (Industrial example)

The first extraction: enamel percolator volume of 100 liters, equipped with a jacket and a "false" bottom load 25,0 kg of grass with roots and rhizomes of iris fine leaved. In polymer drum of 200 l put 73,5 kg (60,5 l) of the extract obtained in the second extraction previous boot, and 50.0 kg of sorbitol (food), 0.25 kg of potassium sorbate (food) and 0.5 kg of ascorbic acid (FS 42-2668-95). The mixture is stirred shaft, then using a vacuum to take in percolator. Include a thermostat set at 90°C; the beginning of the shutter count from the moment when the temperature of the mass in the upper part of percolator reaches 60°C. under these conditions stand before the termination of the growth in the concentration of flavonoids in the liquid phase. Then on the top flange of percolator set enameled grill and filter-package of two polyterephthalate filter cloths, between which is placed a layer of medical (sterile) wool thickness of 5 see Percolator overturn and create pressure 3 ATM supply of inert gas. The hot filtrate is collected in plastic drum of 200 l, pre-treated 70% ethanol solution. Get 62,5 kg (50,0 l) ex is rakta grass with roots and rhizomes of iris fine leaved ("product").

The second extraction: Percolator return to its original position, remove the filter package. The meal poured the extract obtained in the third extraction previous boot, the amount of 81,0 kg and maintained at a temperature in the reaction mass (60-90°C before the termination of the growth in the concentration of flavonoids in the liquid phase. Then set the filter pack, the extract is filtered in polymer drum under the pressure of the inert gas. The extract is No. 2 in the amount of 73.5 kg), which is used for preparation of the extractant on the first extraction next boot.

The third extraction: percolator vacuum load 75,0 l of purified water and the extraction is carried out meal if (60-90)° before the termination of the growth in the concentration of flavonoids in the liquid phase. Obtained in this extract No. 1 (81,0 kg) is used for the second extraction can be loaded later. thermostat turn off heat and serve water to the cooling system; after cooling to 25 to 30°C. meal unload and transfer for recycling.

Received in the amount of 62.5 kg extract ("product") has the following options:

Table 2
Analysis of the Extract of iris fine leaved (syrup) for THE project.
Least the Finance indicators The requirements of normative documentationThe results of the tests
DescriptionOut of line. Transparent or slightly turbid foaming liquid yellow-brown or brown color with a characteristic odor, Pets loss of natural sediment.Hazy, bubbly brown liquid with a characteristic odor and natural sediment.
AuthenticityUV-spectrophotometry. Absorption spectrum of the test solution in the region from 300 to 500 nm should have the maximum absorption wavelength (392±2) nm.

IndicesThe requirements of normative documentationThe results of the tests
Qualitative reaction for flavonoids. When adding vasoreactive should be observed red-brown color.Red-brown staining
Qualitative reaction on specific flavonoids. Adding 1 N NaOH solution Dol is Yong painted in intense brown color. Intense brown color
Qualitative reaction on specific components. Adding zinc dust to the solution becomes red color.Red staining
pHGF XI; potentiometric (original solution). From 3.5 to 5.04,3
Density, g/cm3From 1.00 to 1.351,03
The dry residue, %GF XI. At least 0.50,9
Heavy metals, %GF XII. Not more than 0.001Less than 0.001
GF XII, part 1, page 160. Category 3 B.PI No. 1123/1172-l from 11.11.2012, LLC "Expert Bio"
The total number of aerobic bacteria - not more than 104in 1 mlLess than 104
Microbiological purityThe total number of fungi - not more than 102in 1 mlLess than 10
The absence of E. coli in 1 ml No
The absence of Salmonella in 10 mlNo
Enterobacteria is not more than 102in 1 mlLess than 10
No St. Aureus in 1 mlNo

IndicesThe requirements of normative documentationThe results of the tests
Quantitative determination:
The total content of flavonoids in terms of apigenin, mg/mlUV-spectrophotometry. Not less than 0.3.1,0
The content of polyphenols in terms of Gallic acid (mg/mlUV-spectrophotometry. Not less than 2.5.5,6
The content of sorbitol, %.TLC. At least 30.53
The content of sorbic acid, mg/mlGLC. Not less than 0.1 and not more than 6.03,3
The content of polysaccharides (mg/mlUV-spectrophotometry. Not less than 5.0.62,9
The total content of iridoids, mg/mlUV-spectrophotometry. Not less than 0.3.0,6

CONCLUSION: THE SAMPLE MEETS THE REQUIREMENTS OF SPECIFICATIONS.

Example 12 (the study of the acute toxicity)

The definition of indicators of acute toxicity included experiments on rodents (mice, rats).

The recorded parameters: mortality, time of death, symptoms of poisoning, daily observation of the General condition and behavior, weighing, feed and water intake, dissection and macroscopic description of the precarious and all surviving animals at the end of the study (euthanasia was carried out by an overdose of ether), evaluation of local irritation, determining the mass coefficients of internal organs.

The drug was administered to white rats and mice of both sexes (6 animals of the same sex) intragastrically (W/W) through atraumatically probe in increasing doses according to the Litchfield-Wilcoxon signed. The follow-up period was 14 days.

The studied dose range was 5000, 10000 and 15000 mg/kg (µl/kg). The high dose was achieved by repeated injections of the drug at intervals of 30 minutes. Control of the LM is now received a similar volume of distilled water every 30 minutes (the maximum amount of solvent).

In none of the experimental groups, either in mice or in rats, mortality was not observed. The General condition and behavior of the animals corresponded to normal.

In tables 3-4 shows the mass ratios of the internal organs of mice and rats averaged over groups. Any significant differences between the groups were not found.

Table 3
The mass ratios of the organs of mice (g/kg body weight) in acute intragastric administration of a drug "Afroman syrup for oral administration"
BodyThe experimental group
Control"Afroman syrup"
MFMF
Heart3.7±0.13.4±0.43.5±0.23.6±0.5
Lungs with trachea6.2±0.16.6±0.36.4±0.36.8±0.1
The thymus0.89±0.080.87±0.080.90±0.070.85±0.05
Liver40.1±2.737.4±2.538.5±0.636.3±1.3
Spleen3.4±0.53.4±0.53.0±0.13.0±0.1
Kidney (left)4.2±0.64.7±0.24.6±0.34.4±0.3
The adrenal glands0.18±0.010.15±0.010.19±0.020.15±0.01
The brain15.9±0.416.3±0.714.0±0.415.4±0.7
The testes or ovaries3.3±0.20.20±0.033.5±0.20.19±0.03

Table 4
Mass (µ) organs in albino rats (g/kg body weight) in acute intragastric administration of a drug "Afroman syrup for oral administration"
BodyThe experimental group
Control"Afroman syrup"
MFMF
Heart4.2±0.34.2±0.14.1±0.44.4±0.3
Lungs with trachea7.6±0.28.4±0.67.8±0.28.3±0.3
The thymus1.42±0.101.29±0.101.20±0.081.26±0.11
Liver37.9±1.437.4±2.136.8±1.934.7±1.3
Spleen3.5±0.13.7±0.13.9±0.3 3.7±0.2
Kidney (left)4.2±0.34.3±0.35.0±0.34.5±0.1
The adrenal glands0.10±0.010.10±0.010.10±0.010.11±0.01
The brain8.5±0.58.7±0.38.9±0.29.1±0.5
The testes or ovaries12.3±0.60.26±0.0212.4±0.70.22±0.03

Thus, according to the necropsy acute intragastric administration of the drug "Afroman syrup for oral administration" does not cause macroscopic changes in the internal organs, organs of the endocrine system and brain of Wistar white rats, and is not accompanied by inflammation or irritation of the mucous membranes of the stomach and intestines.

The results of toxicometric - necropsy data allow us to classify dosage form of the drug "Afroman syrup for oral administration" to the V class is practically non-toxic drugs (N. Hodge et al. Clinical Toxicology of Commercial Products. Acute Posoning. Ed. IV, Baltimore, 1975, 427 p). The condition of the animals after acute administration of the drug shows good tolerability and safety of the drug in doses exceeding the maximum therapeutic (about 0.5 ml/kg (500 ál/kg, 500 mg/kg), on the basis of 30 ml per day for the average human weighing 60 kg) dozens of times.

In addition, the results of toxicometric allow us to classify drug "Afroman syrup for oral administration" as a chemical compound to the low hazard substances (IV hazard class according to GOST 12.1.007-76).

Example 13 (the Study of subacute and chronic toxicity)

Given the low toxicity of the drug, shown in the acute experiment, the recommendations of normative documents of the MOH CF RF and GLP regulations and the maximum therapeutic dose (500 mg/kg), for the evaluation of the subacute toxicity was selected period of 1 month, and chronic introduction was carried out for 3 months.

Animals: Rats of both sexes, nonlinear, mass 180-190,

Mongrel dogs of both sexes, weighing 10-16 kg

Route of administration: Intragastrically (Rat - through noninvasive probe; dogs in the throat through the mouthpiece and down using a rubber probe through a large syringe Jean).

Dose:

1 dose of 500 mg/kg - maximum daily human dose;

2 dose of 5000 mg/kg (10 times more);

3 dose - 10000 mg/kg (20 times more). To take a high dose-is difficult. At this dose, each rat received more than 2 ml of the drug, which is almost the limit for rats in the/W introduction.

The number of animals. Rats: 15 animals of each sex per group:

1 dose of 15 males, 15 females;

2 dose of 15 males, 15 females;

3 dose of 15 males, 15 females;

Control - 15 males, 15 females.

The total number of 120, and 30 to the control group.

Dogs: 3 animals of each sex per group:

1 dose of 3 males, 3 females;

2 dose - 3 males, 3 females;

3 dose 3 males, 3 females;

Control - 3 males, 3 females.

The total number is 24, 6 control group.

The duration of observations: Total duration of follow - 90 days.

After injection the animals of all groups were euthanized and subjected to autopsy and pathological examination.

Check indicators: General condition was estimated by daily inspection of the animal. Weighing, measuring rectal temperature, consumption of water and feed were performed once a week during the first month, then 1 time per month and after the injection.

Physiological, hematological and biochemical investigations were carried out before the start of the experiment, after 30 and 90 days after the beginning of the study.

Bone marrow, macroscopic and histological examination of internal organs was conducted after the introduction and the last is the total mortification.

The studies found that the drug does not have a cumulative effect, causing no change in the frequency of cardiovascular abbreviations and nature of the ECG does not change the duration geksenalovy sleep (i.e., no negative impact on the detoxifying function of the liver), no effect on morphological indices of peripheral blood, activity of enzymes and electrolyte composition of blood plasma, myelogram blood (blood-forming organs). Load samples with phenol red showed no violations of the secretory function of the kidneys.

According to the results of the necropsy and histological examination daily intragastric administration of the drug "Afroman syrup for oral administration in doses of 500, 5000 and 10000 mg/kg for 90 days in rats and dogs of both sexes does not cause irritation, inflammation or destruction of tissue, and is not accompanied by the development of dystrophic and destructive, focal sclerotic changes in parenchymatous cells and stroma of internal organs.

Evidence of these claims are given in the report on the experimental pre-clinical study of the safety and pharmacological activity of the drug "Afroman syrup for oral administration" production LLC PharmaMed", EKATERINBURG it FMBA of Russia, Saint-Petersburg, 2012. The proposal does not appear in the possible to lead such a large data array.

In the determination of biochemical parameters of peripheral blood was observed a significant decrease of glucose level (see table 3, 4).

Example 14 (the Study of the pharmacological activity)

Materials and methods

For modeling toxic nefrosonefrit used ethylene glycol, which was administered once in a/W at a dose of 2.5 g/kg to rats-males standard mass (160-170 g) through the metal noninvasive probe.

"Afroman syrup for oral administration" began to introduce/W with 3-day dose of 5000 mg/kg for 10 days.

Drug comparison Lisipril was administered at a dose of 3 ml/kg 3000 mg/kg)/W 2 times a day, morning and evening (at the manufacturer's recommended doses). "Afroman" and Lisipril introduced animals perse.

The drug "Lesperon" is an aqueous-alcoholic solution of purified extract of lespedeza dichroic (Lespedeza Bicolor), which is used in the treatment of chronic renal failure of different origin. It is manufactured by CJSC "Vifiteh" (Moscow region, p. Obolensk). Series 050610, valid until 01.2013,

Ethylene glycol was chosen because it is known that he calls the classical renal disease with renal failure and oligarchism the syndrome is Ohm [Ryabov S. I. Kidney diseases. L., "Medicine", 1982, S. 432].

Just been formed 4 experimental groups (each experimental group consisted of 10 animals):

1. Intact animals.

2. Animals with intoxication without treatment.

3. Animals with intoxication and treatment Esperilla.

4. Animals with intoxication and treatment "Netrokona syrup for oral administration"

The dynamics of the weight of the rats and the relative weight of the kidney to body weight was determined on the scales VLR-500. The kidneys of the animals were weighed on electronic scales 1602 Mr German company "Sartorius".

Daily urine was collected by placing the animals in metabolic cages Italian firm "Texnoplast". Urine analysis was performed by standard methods [Laboratory methods in the clinic. Handbook edited by centuries Menshikov. M, "Medicine", 1987, S. 365].

Blood for biochemical analysis were obtained by puncture of the tail vein of rats.

The activity of glomerular filtration rate (KF), lactate dehydrogenase (LDH), urea and creatinine in serum, urine protein was determined using sets of Bio-Lat-Test of the Czech company "Lachema", the content of ceruloplasmin - by Babenko [Clinical evaluation of laboratory tests. Ed. by N.. Tietz, M, "Medicine", 1986, S. 480].

Mortified by decapitation, the animals were subjected to autopsy the autopsy and histological examination./p>

Statistical processing of results of experiments conducted by the Student-Fisher.

The results of the study

The effectiveness of the "Netrokona syrup for oral administration, and drug comparisons were evaluated by several groups of indicators: morphometric, biochemical, and functional. First of all, the observed clinical picture of intoxication. The clinical picture in the group of rats that received the glycol without treatment, was characterized by physical inactivity, lethargy, theresaknott wool, untidiness animals. They are worse gaining weight than other rats. On day 2 they developed makrogematuriya, and from the 4th day was growing oliguria (table 7).

All animals without treatment developed symptoms of kidney damage in the urine was determined erythrocytes, protein, cylinders, crystals of calcium oxalate, the cells of the renal epithelium. All suffered renal function: secretory, excretory, secretory; blood was growing products of nitrogen metabolism, indicators of cytolysis. Without treatment, the animal was disturbed concentration kidney function (oliguria, urine alkaline, specific gravity, chloride reduced); violated the filtration function of the kidneys (glucose, protein, urea, creatinine increased); reduced secretory function of the kidneys (decreased secretion of phenolic KRA is nogo); developed degeneration of the nephron (cylinders, erythrocytes, leukocytes). Four animals without treatment by the end of the period of the study were killed.

The morphological examination of the kidney showed degenerative changes and minor bleeding into the parenchyma of the organs. In preparations stained with Sudan, was observed fatty neuroepithelial in the cytoplasm of the cells of the convoluted tubules were visible droplets of fat (Fig.1). On histological preparations stained with hematoxylin-eosin, were visible signs of protein malnutrition epithelium proximally tubules. Cell borders were indistinguishable, cytoplasm were intensively stained by eosin, cores were pinnatifida (Fig.2).

The use of "Netrokona syrup for intake and the comparison drug caused pronounced therapeutic effect. Normalized morphometric, biochemical and functional characteristics of the kidney, as evidenced by the data in table 7. This was confirmed by histological examination, where there was virtually no signs of degenerative changes neuroepithelial (Fig.3).

Application Lesparre was less effective than "Netrokona syrup for oral administration".

The results showed that "Afroman syrup for oral administration restores renal function in severe nefrosonefrit caused ethylenglycol is eat. "Afroman syrup for oral administration has been effectively registered healthcare of the Russian Federation funds Lisipril used in renal failure of various origins.

1. Medicine with nephroprotective effect, containing an extract of the herb with roots and rhizomes of fine leaved iris (Iris tenuifolia), stabilizers and preservatives in the following ratio of components, wt.%:

an extract of the herb with roots and98,4-99.89 per
rhizomes of iris
fine leaved (Iris tenuifolia)
stabilizers0,1-1,0
preservatives0,01-0,6

where the extract is obtained by extraction of grass with roots and rhizomes of fine leaved iris (Iris tenuifolia) 30-70% aqueous solution of a polyhydric alcohol.

2. Drug under item 1, characterized in that as stabilizers use of ascorbic acid, if the pH is maintained within the range from 3.5 to 5.0.

3. Drug under item 1, characterized in that used as preservatives benzoic acid or its pharmaceutically acceptable the s salt at a concentration of 0.01-0.5 wt.% and/or sorbic acid or its pharmaceutically acceptable salt in a concentration of 0.01-0.6 wt.%.



 

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Phosphate adsorbent // 2527682

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20 cl, 10 dwg, 5 tbl, 16 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula , wherein A means a six-merous aryl radical or a five-merous heteroaryl radical which contains one heteroatom specified in oxygen and sulphur; one or more hydrogen atoms in the above aryl or heteroaryl radicals can be substituted by substituting groups R1 which are independently specified in a group consisting of: F, Cl, Br, I, (C1-C10)-alkyl-, (C1-C10)-alkoxy-, -NR13R14; B means a radical with mono- or condensed bicyclic rings specified in a group consisting of: six-ten-merous aryl radicals, five-ten-merous heteroaryl radicals and nine-fourteen-merous cycloheteroalkylaryl radicals, wherein cycloheteroalkyl links can be saturated or partially unsaturated, while the heterocyclic groups can contain one or more heteroatoms specified in a group consisting of nitrogen, oxygen and sulphur, one or more hydrogen atoms in the radical groups B can be substituted by substituting groups R5 (as specified in the patent claim), L means a covalent bond, X means the group -O-, R2 is absent or means one or more substitutes specified in F and (C1-C4)-alkyl radical; R3 and R4 independently mean (C1-C10)-alkyl, (C3-C14)-cycloalkyl, (C4-C20)-cycloalkylalkyl, (C2-C19)-cycloheteroalkyl, (C3-C19)-cycloheteroalkylalkyl, (C6-C10)-aryl, (C7-C20)-arylalkyl, (C1-C9)-heteroaryl, (C2-C19)-heteroarylalkyl radicals, or R3 and R4 together with nitrogen attached whereto can form a four-ten-merous saturated, unsaturated or partially unsaturated heterocyclic compound which can additionally contain one or more heteroatoms among -O-, -S(O)n-, =N- and -NR8-; other radicals are such as specified in the patient claim. Also, the invention refers to using the compound of formula I for preparing a drug.

EFFECT: compounds of formula (I) as Na+/H+ metabolism inhibitors NHE3.

22 cl, 27 dwg, 1 tbl, 756 ex

FIELD: chemistry.

SUBSTANCE: described are novel compounds of general formula ,

where X equals 1 or 2; Y equals 0 1, 2, or 3; R1 is hydrogen, C1-2alkyl or C1-2alkoxy; A denotes 2,6,-dimethylphenyl, a pharmaceutical composition containing same, a method of reducing concentration of uric acid in blood or increasing release of uric acid in a mammalian subject, and use the novel compounds to obtain a medicinal agent for treating, particularly, gout and hyperuricemia.

EFFECT: obtaining a medicinal agent for treating gout and hyperuricemia.

30 cl, 9 dwg, 17 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine and aims at treating patients with renal dysfunction. There are described a method for nephroprotection and a method for blood serum creatinine reduction in a mammal in need thereof. At least one compound described by the formula Y=O, NH, or at least one compound described by the formula , or a combination thereof, wherein R1 means a linear or branched, saturated or unsaturated C7-C11 alkyl group; A and B independently represents hydrogen or , and X represents a hydroxyl group, oxy anion with one- or two-valent metal counter-ions or an alkoxy group with a linear or branched C1-C4 alkyl residue is introduced into the mammal.

EFFECT: using the declared group of inventions is effective in treating the patients with renal dysfunction caused by fibrosis, and for reducing creatinine.

18 cl, 14 dwg, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to compositions and methods for prevention or treatment of renal fibrosis in an individual. Particularly, the method for prevention or treatment of renal fibrosis in an individual involves administering a composition containing a pharmaceutically effective amount of a vasoactive intestinal peptide (VIP) or one or more functional VIP fragments specified in VIP(10-28), VIP(4-12), VIP(4-16), VIP(4-20), VIP(4-24), VIP(6-10), VIP(6-12), VIP(6-16), VIP(6-20), VIP(6-24) or conventional substitutes thereof into the individual exposed to a risk of developing renal fibrosis or suffering from renal fibrosis.

EFFECT: using the group of invention enables preventing or delaying developing renal fibrosis in the individual more effectively.

15 cl, 4 dwg, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to a method of treating or preventing renal diseases in a domestic animal by feeding a nutrient compound. The compound contains one or more pyruvates an amount of which is sufficient for treating or preventing the above diseases. Pyruvates may be presented by: calcium pyruvate, sodium pyruvate, lithium pyruvate, potassium pyruvate, magnesium pyruvate, zinc pyruvate, manganese pyruvate and a combination thereof. The domestic animal is a cat or a dog.

EFFECT: preventing renal diseases.

6 cl, 6 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: described are novel 2-pyridyl-substituted imidazoles of general formula (I) , where Ra is C1-6alkyl; m = 1; A1 = N; A2 = NR1, where R1 is hydrogen; X is bond, -NR2-, -O- or -S-, where R2 is hydrogen or C1-3alkyl; Rb independently is H, halogen, C1-6alkyl, C2-6alkenyl, C2-6alkinyl, -(CH2)q-OR3, where R3 - C1-6alkyl or C1-6halogene alkyl, and q=0,1, -(CH2)q-NR3R4, where R3 and R4 independently are C1-6alkyl or together with nitrogen atom - pyrrolidinyl or morpholinyl, and q=0-2; -SR3, where R3 - C1-6alkyl, -(CH2)q-CN, where q=0 or 1, -COR3 or -CO2R3, where R3 is C1-6alkyl, -CONR3R4, where R3 and R4 is hydrogen, -NHCOR3 or -NHSO2R3, where R3 stands for C1-6alkyl; n equals 0, 1, 2, 3, 4 or 5; or their pharmaceutically acceptable salts, or hydrates and pharmaceutically acceptable compositions for treatment or abatement of metastasis of tumour cells, carcinomas, fibrosis by inhibiting pathways of transmission of signal of TGF-β or activin, or both.

EFFECT: improvement of composition properties.

6 cl, 6 tbl, 7 ex, 33 dwg

FIELD: veterinary science.

SUBSTANCE: preparation of local therapy contains pine resin, chlorophyll carotin paste, birch oil, castor oil in the following proportions: pine resin: chlorophyll carotin paste: birch oil: castor oil - 10:5:5:80.

EFFECT: using the declared preparation enables the higher therapeutic effect as compared to the existing agents for treating animal skin diseases, including dermatitis.

1 ex

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