RU2611648C1 - Method of production of purgative agent from grass of field restharrow - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to the pharmaceutical industry, particularly, to the method of production of a purgative agent. The method of production of a purgative agent from the grass of the field restharrow including the dry grinding of the grass of the field restharrow by a squeezing and mastication, extraction of the water and methanol solution. Whereupon, before extraction of active substances (for the extraction, 50% water and ethanol solution containing 1 mass.% of citric acid), the infusion of grinded grass is performed in the same solution, as well as purification of the obtained solution from resinous substances via passing it through a layer of a silica-gel under certain conditions.

EFFECT: method of production of an effective purgative agent with the high concentration of the active substances in it.

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Description

The invention relates to medicine, and relates to the creation of a laxative of plant origin from grass of a field steel.

The group of laxatives registered in the Russian Federation is represented mainly by herbal medicines (herbal remedies). This is due to the fact that herbal remedies are more harmless and safe, have fewer side effects, are physiologically closer to the human body than synthetic ones. Being complex in their chemical composition, they contain a diverse set of biologically active substances that give them extremely valuable properties and provide a multilateral effect on the body [1].

It is known laxative of plant origin, containing the amount of antraglycosides of the leaves of senna (cassia), - antrasennin. The technology for obtaining this drug is as follows. The crushed senna leaves with up to 3% anthraglycosides content are extracted three times with 65% alcohol for 1 hour with stirring (raw material: extractant ratio 1: 7). Then evaporate the water-alcohol extract in a circulating vacuum evaporator at 40 ° C to 1/10 of the original volume. The aqueous bottoms are settled at 8-10 ° C for 3 hours. Water-insoluble resins separated in a centrifuge precipitate. Next, a 10% solution of calcium chloride (16: 1) is added to an aqueous solution with anthraglycosides with stirring, stirred for 15-20 minutes, then a mixture of ammonia with alcohol is added, strictly maintaining the pH of the mixture in the range of 6.5-6.7. When precipitated with alcohol, a reddish-brown color appears, a flocculent precipitate of calcium salts of anthraglycosides forms, which is separated in a centrifuge. The filter cake was washed with acetone and dried at 35-40 ° C in a vacuum dryer. A powder is obtained from light to dark brown, hygroscopic, soluble in water. The yield of anthrasennine is 50% of the content of anthraglycosides in the feed [2].

The proposed method in its practical implementation in pharmaceutical production has several disadvantages:

1. The technological scheme for the production of herbal medicine is complex and lengthy;

2. Low yield of the current group of substances - the amount of anthraglycosides;

3. The technological scheme provides for the use of a sufficiently toxic organic solvent - acetone, the use of vacuum evaporation systems;

4. The disadvantages of anthrasennin and, in general, antraglycoside-containing preparations include the following. The systematic administration of these phytochemicals leads to the development of a number of serious side effects, such as melanosis of the intestinal mucosa, severe liver dysfunction, abdominal pain in the abdomen, colitis, cramps, vascular collapse, impaired water-electrolyte metabolism, and increased blood pressure. Tolerance to these drugs also occurs, which requires an increase in their dose with prolonged use. In addition, their laxative effect occurs 5-10 hours after administration. This is due to the fact that anthraglycosides per se are not active. They are slowly hydrolyzed by enzymes and bacterial flora of the large intestine in an alkaline medium with the release of aglycones. In addition, they are contraindicated in intestinal, uterine bleeding, acute and chronic glomerulonephritis, ulcerative colitis, intestinal obstruction, peritonitis, cystitis, decompensated diabetes mellitus, as well as in spastic constipation and hemorrhoids. They should not be prescribed to children and combined with antibiotics, especially with tetracyclines, since they disrupt their absorption. It is also important to note the fact that recently some European countries have practically abandoned the use of anthranoid drugs, due to their genotoxic and mutagenic properties [3].

It is known that alcohol tincture from the roots of a field steel be used as a therapeutic laxative, which is a clear reddish-brown liquid with a regulated concentration of isoflavonoids as an active group of tincture substances at a level of at least 0.2% by mass, with a dry solids content of at least 2% of the mass. Stalnik tincture contains isoflavonoids (ononin, onospin), tannins, triterpene saponins, resins, citric acid, starch, essential oil. Stalnik tincture is prescribed inside, 30 minutes before a meal: 1 / 2-1 teaspoon of tincture is taken in 1/4 cup of water, 2-3 times a day. The course of treatment is 2-3 weeks [4,5].

However, the tincture of the roots of the field stalnik has several disadvantages: the presence of resins, a low concentration of biologically active substances, including the active group — isoflavonoids (0.2% mass);

The closest in technical essence and effectiveness of the treatment of chronic constipation and hemorrhoids, taken as the closest analogue [6], is a liquid extract of grass of field steel, obtained by extraction at a ratio of (raw material: finished product) 1: 2. A method of obtaining a laxative from a field steel Ononis arvensis L. is as follows. The dry steel of the steel, crushed by the principle of simultaneous crushing and abrasion to a particle size of not more than 1.0 mm, is uniformly loaded into the extractor-diffuser. Then the raw material is extracted without extracting with a 70% aqueous solution of ethyl alcohol in the ratio (raw material 6 extractant) 1: 2, constantly maintaining the “mirror” of the extractant. The duration of the process of extraction of raw materials is 6 hours. The concentration of biologically active substances, including the active group - isoflavonoids - 0.59% mass. The resulting liquid extract is defended, filtered and packaged.

Disadvantages:

The extraction conditions and its implementation do not allow to implement the process of ethanolysis of the feed due to the neutral pH of the aqueous-alcoholic solution, which does not contribute to the achievement of the maximum amount of active substance. Mixing of the extracted medium is not provided, which complicates the extraction processes. The high content of ethyl alcohol in the solution leads to the extraction of vegetable resins and other minor substances that degrade the overall quality of the laxative - precipitation forms during storage.

The objective of the invention is to develop an effective method for producing a laxative from a field steel, expanding the assortment of this group of phytochemicals, increasing the concentration of the active group of biologically active substances, improving the production process of a laxative while maintaining this type of activity, using dry grass of a field steel as a laxative containing a rich complex of biologically active substances (BAS).

The problem is realized by the method consisting in obtaining a laxative from dry grass of the field steel, including grinding it with simultaneous crushing and abrasion to a particle size of not more than 1.0 mm, insisting for 0.5 hours in an aqueous solution of 50% by volume ethyl alcohol and 1% mass citric acid, extraction with stirring with the same solution for 1 hour in the ratio of raw materials: extractant, respectively 1: 2, purification of resinous substances by passing 0.2-0.3 m fractions through a silica gel layer .

The technical result is achieved by improving the quality of the finished product by increasing the yield of the active group of substances - isoflavonoids, in terms of ononin (1.5% mass), extractive substances and improving the conditions of the extraction process by introducing citric acid into the extracting solution, purifying the obtained extract with silica gel .

A method of obtaining a laxative from grass stalnik field Ononis arvensis L. is as follows. The dry steel of the steel, crushed by the principle of simultaneous crushing and abrasion to a particle size of not more than 1.0 mm, is uniformly loaded into an extractor-diffuser of a known type. Then the raw material after 30 minutes of infusion in an aqueous-alcoholic solution at a temperature of 20-25 ° C, is extracted with stirring with a 50% by volume aqueous-alcoholic solution with 1% mass citric acid in the ratio (raw material: extractant) 1: 2, constantly keeping the “mirror” of the extractant for 1 hour. The total duration of the extraction process of raw materials is 1.5 hours. Then carry out the cleaning of extraneous resinous substances of the obtained extract by passing it through a layer of silica gel fraction 0.2-0.3 mm The resulting purified liquid extract is filtered and Packed.

The proposed method allows to obtain a finished product, which is a clear liquid of greenish color with a slight grassy odor. At the same time, the share of biologically active substances (“dry residue”) transferred from raw materials to the extraction is 90%. The extraction efficiency for isoflavonoids is about 95%, which ensures the concentration of this active group of substances in the liquid extract at the level of 1.5% mass.

In order to select the optimal extractant composition for the preparation of a laxative from field steel grass, the phytochemical composition and pharmacological activity of 40%, 50%, 60% and 70% (volumetric) water-alcohol extracts with and without citric acid (food grade) were studied. As a result of the studies, it was found that 50% (volumetric) water-alcohol extraction with 1% by mass of citric acid is the most rich in phenolic compounds in qualitative and quantitative composition and is easier to purify with silica gel. A study of pharmacological activity, namely, the laxative effect in relation to the above extracts, showed that 50% (volumetric) water-alcohol with 1% by mass citric acid extract from the steel of the steel increased the tone and intestinal motility more than 40%, 60%, 70% water-alcohol purified extracts.

The results of studying the dynamics of extraction revealed a characteristic feature of the extraction behavior of flavonoids and isoflavonoids of grass of field steel when using rolled raw materials and 50% (volumetric) aqueous-alcoholic solution with 1% mass citric acid, which consisted in their maximum transition from raw materials to the first two plums obtained. In this case, citric acid replaced the active groups of natural polymers associated with isoflavonoids, and subsequently did not significantly affect the taste of a laxative. Silica gel provided purification of a laxative from plant resins and minor substances.

Thus, the proposed method and the degree of grinding of raw materials (not more than 1.0 mm), the optimal concentration of ethyl alcohol (50% by volume) and 1% by mass of citric acid as an extractant, as well as the removal rate of the finished product 1: 2, silica gel purification at obtaining a laxative from grass stalnik field, are optimal from a technological point of view and ensure the achievement of the desired pharmacological effect.

Obtained by the proposed method, the laxative contains a rich and diverse complex of biologically active substances, such as flavonoids, phenolcarboxylic acids, tannins, triterpene saponins, organic acids. Flavonoids presented in the proposed drug have an antimicrobial, choleretic effect, strengthen the walls of capillaries, increase their elasticity, increase oxygen consumption by the arterial wall, lower blood pressure; have anti-inflammatory, bactericidal, diuretic and estrogenic effects. In addition, flavonoids play the role of antioxidants - substances that prevent the non-enzymatic peroxidation of organic compounds or significantly slow it down.

Phenolcarboxylic acids in the composition of the claimed funds also exhibit choleretic, antioxidant, antibacterial, anti-inflammatory activity. In addition, phenological glycosides have a disinfecting effect on the genitourinary system and have a diuretic effect.

Saponins regulate water-salt metabolism, have anti-inflammatory and laxative effects, lower blood pressure. In addition, they have a stimulating, adaptogenic, diaphoretic, restorative effect.

As for tannins, they have a local hemostatic effect, have astringent, bactericidal properties in the treatment of gastrointestinal diseases, namely with acute and chronic diarrhea, enterocolitis. Organic acids are actively involved in the metabolism, activate the secretion of bile, pancreatic juice, have a bactericidal effect, reduce putrefactive processes in the intestine. In addition, this group of natural substances enhances the excretion of digestive juices and intestinal motility.

In general, active substances increase the tone of the intestinal wall, reduce the blood supply to hemorrhoidal veins and swelling of the hemorrhoidal nodes, and facilitate the bowel movement. In addition, the active substances have an anti-inflammatory effect and prevent thrombosis. Isoflavonoids and saponins stabilize cell membranes, reduce vascular permeability.

The invention is illustrated by the following examples.

Example 1. 100.0 g of grass steel, crushed by the principle of simultaneous crushing and abrasion to a particle size of not more than 1.0 mm, was uniformly loaded into the extractor-diffuser. Then the feed was infused for 0.5 hours in a 50% (volume) aqueous ethanol solution with 1% by mass of citric acid and extracted with stirring for 1 hour a 50% (volume) water-ethanol solution with 1% by mass of citric acid in the ratio (feed : extractant) 1: 2, constantly maintaining the “mirror” of the extractant. The duration of the extraction process of raw materials was 1.5 hours. The obtained liquid extract was defended, subjected to purification by passing 0.2-0.3 mm fractions through silica gel, filtered and sent to the packaging. Silica gel was subjected to regeneration and used for cleaning repeatedly.

Result: the extraction efficiency of the amount of biologically active substances in the liquid extract was 95%, and the concentration of isoflavonoids was 1.5% by mass.

Example 2. Similar to the prototype method. Result: the concentration of isoflavonoids is 0.61% mass.

Tests have shown that the proposed remedy from the grass of the field steel, with a laxative effect, refers to substances of toxicity class IV, i.e. It is low hazard to human health. The study of the effect of purified water-alcohol extraction of field steel from grass on the motility of the gastrointestinal tract was carried out in experiments on rats of both sexes, weighing 220-260 g. For 20 hours before the experiment, the animals did not receive food. The amount of water was not limited. A 5% suspension of activated carbon in 2% starch mucus was injected into the stomach with rats using a probe. After 15 minutes, aqueous solutions of steel extracts (in terms of solids) were poured intragastrically at a dose of 15.0 mg / kg. 2 hours after the administration of the studied objects, the animals were sacrificed under ether anesthesia, the stomach and small intestine were opened and removed, without separating them from each other. Then they were stretched under a load of 3 grams, the distance of coal advancement in the intestine was measured with a meter, and an indicator of the intensity of intestinal motility relative to the control was calculated. Analysis of the results allowed us to conclude that in the control experiment, the rate of advancement of activated carbon in the intestines was 121.8 ± 6.2 cm. When the extract obtained according to the prototype was introduced, the coal advanced by 152.5 ± 5.1 cm, then there is 25.2% further in comparison with the control. With the introduction of the liquid extract obtained according to the proposed method (example 1), the coal advanced 182.2 ± 5.6 cm, that is, 19.5% further than for the prototype method (example 2), and 49.6 % further than for control. All of the above, allows us to conclude that the laxative activity of the prototype is significantly lower than that of the funds obtained by the proposed method.

The simplicity of the process makes it possible to create mass production of an effective domestic laxative drug and expand the range of laxative herbal remedies.

In general, it should be noted that the invention in comparison with the prototype has the following advantages:

- the target product (liquid extract of grass stalnik field) has a significantly greater laxative activity than the prototype (liquid extract of grass stalnik field 70% volume of water-alcohol extraction);

- obtaining a laxative from dry grass of the field stalnik is more economical: the extraction time is reduced by 4 times (instead of 6 hours, extraction is carried out for 1.5 hours), effective purification of the laxative by silica gel from resins and minor substances;

- the proposed laxative technology allows extracting about 95% of the amount of biologically active substances from the grass of the stalnik and ensuring the concentration of active substances in the target product at the level of 1.5% by weight, which is 2.54 times higher than in the case of the prototype.

Bibliography

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2. Minina S.A. Chemistry and technology of phytopreparations / S.A. Minina, I.E. Kaukhova.- M .: GEOTAR - Honey, 2004 .-- 560 p.

3. Lesiovskaya E.E. Pharmacotherapy with the basics of herbal medicine: Textbook. allowance / E.E. Lesiovskaya, L.V. Shepherdesses. - 2nd ed. - M .: GEOTAR-MED, 2003 .-- S. 297-333.

4. Kovalev V.N. Chemical study of isoflavonoids contained in tincture of steel / V.N. Kovalev // Modern methods for the study of medicinal plants: Sat. scientific tr - M., 1988 .-- S. 96-103.

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6. Sampiev A.M. Development of active substance-oriented technology of liquid extract of grass steel / A.M. Sampiev, N.A. Davitavyan // Bulletin of Voronezh State University. Series: Chemistry. Biology. Pharmacy. - 2011. - No. 2. - S. 199-203.

Claims (1)

A method of obtaining a laxative from grass of field steel, including grinding dry grass of steel, providing for crushing and abrasion to a particle size of not more than 1.0 mm, extraction with an aqueous-ethanol solution for 1 hour in the ratio of raw material: extractant, respectively, 1: 2 and characterized in that before extraction of the active substances, the crushed grass is infused in the same solution for 0.5 hours; for extraction, a 50% by volume aqueous ethanol solution containing 1 wt.% citric acid is used you, and carry out the purification of the obtained extract from resinous substances by passing 0.2-0.3 mm fractions through a layer of silica gel.