RU2683570C1 - Composition for vegetable components, which has the ability to reduce the level of uric acid in blood serum - Google Patents

Abstract

FIELD: pharmaceuticals.

SUBSTANCE: invention refers to pharmaceutical industry, namely to a composition reducing concentration of uric acid in blood serum. Composition is a mixture of plant components milled into 0.01–0.001 mm fractions, taken in ratio, wt%: aspen bark 30–50 %, birch leaf 10–20 %, Filipendula stems 15–30 %, Silybum marianum stems 15–30 %, Achillea stems 10–15 %.

EFFECT: composition is characterized by high solubility in water, bioavailability and efficacy, has no irritant and ulcerogenic action on gastric and intestine mucosa.

1 cl, 1 tbl, 5 ex

Description

The invention relates to medicine.

One of the most serious problems in modern therapy and surgery is impaired uric acid metabolism. As a rule, there are cases of an increase in the level of uric acid that are not associated with genetically determined causes, for example, gout. In this case, the concentration of uric acid in the blood serum increases, followed by the accumulation of uric acid salts in the tissue depots (kidneys, joints, vascular wall). Subsequently, the impairment of urinary acid excretion by the kidneys intensifies, disorders of lipid and carbohydrate metabolism occur, arterial hypertension develops, etc.

One of the most successful drugs to prevent increased uric acid formation is Allopurinol (R. Seth, etal. 2014). The drug blocks the activity of the xanthine oxidase enzyme, preventing the formation of uric acid de novo. The disadvantage of the drug is that it is not able to dissolve crystals of uric acid salts in tissue depots.

Known biological drug Hepatocatalase isolated from beef liver (www.eurolab.ua/diseases/2184). Hepatocatalase reduces the synthesis of endogenous uric acid and increases its breakdown. The main disadvantage is that the drug is parenteral, administered intramuscularly 2-3 times a week. The second disadvantage is frequent allergic reactions to the drug.

Known plant components that can improve the excretion of uric acid salts from the body. In these cases, we are talking about the use of plant extracts containing bioflavonoids and derivatives of organic acids (salicylic, citric, betulonic). However, the human gastrointestinal tract is designed so that most of these substances are either not absorbed or absorbed in extremely small quantities. New perspectives appear when using mechanical methods of processing raw materials in order to obtain supramolecular complexes with high solubility and bioavailability (Dushkin A.V. et al. 2010; Tolstikova T.G., et. Al. 2011). The sum of weak non-covalent bonds keeps the complex from decay, while the resulting compositions acquire new properties: increased solubility, increased bioavailability, and reduced toxicity.

Disclosure of invention

A composition that reduces the concentration of uric acid in the blood serum is a mixture of plant components crushed to a fraction size of 0.01-0.001 mm, taken in the ratio (wt.%): Aspen bark 30-50%, birch leaf 10-20%, stems meadowsweet 15-30%, thistle stalks 15-30%, yarrow stalks 10-15%.

The composition is characterized by increased solubility in water, bioavailability, effectiveness, has no irritating and ulcerogenic effects on the mucous membrane of the stomach and intestines.

The proposed composition incorporates polysaccharide complexing agents and triterpenes, which, as a result of mechanical treatment, form water-soluble complexes with high bioavailability of the general formula R2-R1-R2,

where R1 are hydrophobic compounds (carotenoids, terpenes, triterpenes, glutamine, folic acid, flavonoids, etc.)

R2 - soluble plant polysaccharides complexed by Van der Waals forces with hydrophobic compounds.

As a result, the proposed composition has high solubility, bioavailability and effectiveness.

In order to create complexes, mechanical processing of plant materials is carried out in two stages according to the scheme developed for this composition.

At the first stage, separate machining of each type of source plant material (aspen bark, birch leaf, stalks of meadowsweet, milk thistle, yarrow) is carried out with an initial particle size of less than 1 mm (0.1-1 mm), residual moisture not more than 10% in the following mode:

- loading of the processed material in relation to the loading of grinding media (steel balls with a diameter of 20-25 mm), respectively: 1: (1-2);

- drive rotation speed - 30-50 rpm;

- processing time 4-24 hours to obtain a powder with particle sizes of 0.4 mm or less (0.05-0.4 mm).

At the second stage, the obtained powders of bark of aspen, birch leaf, stalks of milk thistle, yarrow and meadowsweet are mixed in the above proportions, and subjected to repeated mechanical processing in the following mode:

- loading of the processed material in relation to the loading of grinding media - 1: 1-1: 2;

- drive rotation speed - 30-50 rpm;

- processing time 24-30 hours.

Comparison of the quality indicators of the compositions obtained in the second stage at various times of machining (optimized parameter) showed that with a process duration of more than 30 hours, the chemical decomposition of natural organic compounds occurs, thereby reducing their content by less than 80% of theoretical. On the other hand, when the duration of the mechanochemical process is less than 20 hours, the solubility of the treated mixture is not significantly different from the solubility of a simple fragmented mixture, i.e. a mixture of components with a particle size of 0.05-0.4 mm, obtained by processing the raw materials in the first stage before processing in the second stage.

Example 1

Aspen bark, birch leaf, stalks of meadowsweet, milk thistle, yarrow with a particle size of 0.1-1 mm and a residual moisture content of not more than 10% are mechanically crushed in the following mode:

- loading of the processed material - 1.5 kg;

- loading grinding media - steel balls with a diameter of 20 mm - 3 kg;

- drive rotation speed - 50 rpm;

- the time of machining - 24 hours to obtain a powder with a particle size of 0.05-0.4 mm

Further, the obtained powders of bark of aspen, birch leaf, stalks of meadowsweet, milk thistle, and yarrow are mixed in the ratios: aspen bark 40%, white birch leaf 10%, stalks of meadowsweet 20%, thistle stems 20%, yarrow stems 10%. The residual moisture content of the mixture should not exceed 10%.

The resulting mixture is subjected to mechanochemical treatment according to the following scheme:

- loading of the processed material - 1.5 kg;

- loading grinding media - steel balls with a diameter of 20 mm - 2 kg;

- drive rotation speed - 50 rpm;

- machining time - 24 hours

After processing in this mode, the final size of the obtained fraction was 0.01-0.001 mm, the solubility in water of the resulting composition at room temperature was 45%.

Example 2. Assessment of ulcerogenicity

The proposed composition was administered to rats intragastrically on an empty stomach (starvation 12-14 hours) daily for 30 days. After this, the animals were sacrificed and the stomachs were removed to visually assess the condition of the mucosa. After washing with running water, the presence / absence of hyperemia, erosion and ulcers was recorded.

Receiving the proposed composition for 30 days did not cause irritation and / or damage to the gastric mucosa.

Example 3

The soluble fraction extractivity was determined by the gravimetric method after evaporation of the supernatant.

When dissolving a simple fragmented mixture prepared by mixing the components obtained in the first stage in warm (40 ° С) water at the rate of 1 g of the mixture per 100 ml of water, the soluble fraction was 120 mg in solution from 1 g of the initial dry mixture. Upon dissolution of the proposed composition, the yield of the soluble fraction was 3.2 times greater in comparison with a simple mixture (Table 1).

Example 4. We studied the concentration of uric acid in serum in healthy volunteers, but with an increased concentration of uric acid (more than 350 μmol / L in women, and more than 415 μmol / L in men). In the 1st group (control group), volunteers (5 people) received capsules with starch (placebo). In the second control group, volunteers (8 people) received a mixture of plant components in the stated proportion, but without the second stage of mechanical processing at a dose of 0.6 g 2 times a day 15 minutes before meals. In the third group (7 people), volunteers took the proposed composition in the same dose and in the same mode. The duration of administration of drugs was 28 days in all three groups.

Statistical processing of data was carried out in the Statisticav.10 program using the t-test to assess the significance of differences. Data are presented in the format: mean ± standard error of the mean (SE).

In the third group, the average initial value of the concentration of uric acid in blood serum was (M ± m) 455 ± 15 μmol / L. Already 14 days after the start of taking the proposed composition, the level of uric acid decreased to 315 ± 18 μmol / L (p <0.05). In the first group, the uric acid level did not change after 2 and 4 weeks of the study. In the second group, the level of uric acid on the 14th day decreased slightly (from 455 ± 22 μmol / L to 439 ± 40 μmol / L, p> 0.5, the differences were not significant). Significant differences in uric acid concentration were observed in this group only on day 28 (from 455 ± 22 μmol / L to 345 ± 15 μmol / L, p <0.05)

Thus, the proposed composition significantly reduces the level of uric acid in the blood serum and is more effective than a simple mixture of crushed components in the same proportion, but without the second stage of processing.

Example 5. Patient N., 61 years old, with a diagnosis of metabolic syndrome; uric acid diathesis. Complaints of joint pain, high blood pressure. During biochemical examination, blood cholesterol was 6.2 mmol / L, blood sugar (morning) 6.5 mmol / L, uric acid 560 mmol / L. 2 weeks after the start of taking the claimed composition in a dose of 0.6 g 2 times a day 15 minutes before a meal, a significant improvement in well-being, the disappearance of pain in the joints was noted. The results of biochemical analyzes: serum cholesterol 5.2 mmol / l, blood sugar (morning) 6.1 mmol / l, uric acid concentration 365 μmol / l. The use of the claimed composition led to a rapid decrease in uric acid levels to normal values.

LITERATURE.

1. R. Seth, A. Kydd, R. Buchbinder, et al. Allopurinol for chronic gout // Cochrane Database of Systematic Reviews. - 2014

2. Tolstikova T.G., Khvostov M.V., Lifshits G.I., Dushkin A.V., Meteleva E.S. Alteration of Warfarin's Pharmacologic Properties in Clathrates with Glycyrrhizic Acid and Arabinogalactan // Letters in Drug Design & Discovery. 2011. - Vol. 8, No. 3. - P. 201-204.

3. A.B. Dushkin, E.C. Meteleva, T.G. Tolstikova, M.B. Khvostov, M.P. Dolgikh, G.A. Tolstikov. The combination of pharmacons with glycyrrhizic acid is the way to create drugs of increased efficiency // Chemistry in the interests of sustainable development. 2010. - T. 18. No. 4 - S. 517-525.

Claims (1)

A composition that reduces the concentration of uric acid in blood serum is a mixture of crushed to a particle size of 0.01-0.001 mm plant components, taken in the ratio, wt. %: aspen bark 30-50%, birch leaf 10-20%, stalks of meadowsweet 15-30%, stalks of milk thistle 15-30%, stems of yarrow 10-15%.