RU2256463C1 - Medicinal plant species for complex therapy of liver and bile- excreting way diseases in chronic intoxications associated with industrial (technogenic) and domestic toxic effects - Google Patents

Abstract

FIELD: medicine, phytotherapy, chemical-pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to the development of medicinal species for treatment of liver and bile-excreting way diseases. Agent for treatment and prophylaxis of liver and bile-excreting way diseases in chronic intoxications associated with industrial (technogenic) and domestic toxic effects comprises milk thistle fruits, common immortelle flowers, knot-grass (knotweed) herb, marjoram herb, milfoil herb, motherwort herb, wild rose fruits, flax seeds, alder compound fruits, and fungus Inonotus obliquus taken in the definite ratio of components. Agent is made as a solid formulation (tablet) or syrup. Agent can be milled and packaged in filter-bags. Agent is prepared as dry extract for the following industrial processing. Apart from cholagogue effect the agent elicits antioxidant, expressed membrane-protective, analgesic and anti-inflammatory effects.

EFFECT: valuable medicinal properties of species.

5 cl, 7 tbl

Description

The invention relates to medicine, namely to herbal medicine, and can be used for the prevention and treatment of diseases of the liver and biliary tract.

The official collection of choleretic No. 2 (VFS 42-639-77) (immortelle flowers 40%, yarrow grass 20%, peppermint leaves 20%, coriander fruits 20%) is known, has a choleretic, anti-inflammatory and antispasmodic effect (Great Russian Encyclopedia of Medicines . M., “Remedium”, 2001). However, it has a number of drawbacks, in particular, it has no indications of hepatomembranoprotective and antioxidant properties, which makes it necessary to use additional drugs, often synthetic hepatoprotectors and antioxidants, in complex therapy. The latter are known to inhibit the functioning of the immune system (Ball et al., 1986).

The prototype is the drug "Karsil", which is a drug containing the active ingredients of the fruit of milk thistle and used in acute (toxic) hepatitis, for maintenance therapy for chronic liver diseases and cirrhosis. The hepatoprotective effect of “Karsil” is explained by antioxidant activity, as well as by the fact that it stimulates protein synthesis, normalizes the metabolism of phospholipids (Mashkovsky, “Medicines”, 2000). However, the drug “Karsil” does not have an analgesic, membrane-protective and anti-inflammatory effect.

EFFECT: obtaining a hepatoprotective agent having, in addition to the choleretic and antioxidant effects, pronounced membrane-protective, analgesic and anti-inflammatory properties.

The proposed collection, having the trade name "Golden" (hereinafter referred to as the collection) (in the form of a grass collection, in filter bags, dry extract, in the form of special-purpose syrup, in tablet form), contains immortelle flowers, bird of the mountaineer (knotweed), grass oregano, yarrow grass, motherwort grass, milk thistle, rosehips, flax seeds, alder fruit, chaga in the following ratio, wt.%:

immortelle flowers 1.9

grass of the mountaineer bird (knotweed) 3.2

oregano grass 6.3

yarrow grass 12.6

motherwort herb 3.2

milk thistle fruit 12.6

rose hips 19

flax seeds 3.2

alder congestion 19

chaga 19

The collection includes medicinal plants that are approved for use in medical practice (State Pharmacopoeia of the USSR, 11th edition. Issue 2 - M., 1990, GOST 21908-93, GOST 1994-93, TU 9700-005-26795008-02).

The antioxidant effect of the collection, established in the course of research as a pharmacological property belonging to this collection, manifests itself due to the composition of medicinal herbs included in it. Milk thistle fruits are used in the collection, which are part of the well-known preparations “Karsil” and “Silibor”, however, milk thistle fruits are not used in the Global Fund, which forced us to write TU 9700-005-26795008-02. Other components of the collection are immortelle flowers, oregano grass, yarrow grass, rose hips have a choleretic effect (Big Russian Encyclopedia of Medicines. M., Remedium, 2001).

The technology for preparing the collection is that each type of medicinal raw material that meets the requirements of the Gosfarmokopey X and XI edition is ground to a size of not more than 7 mm (for filter bags from 0.2 to 2 mm). Then the medicinal raw materials are weighed and thoroughly mixed in equal parts until a uniform mixture is filtered and sifted out from dust through a sieve with a hole diameter of 0.18 mm. The crushed raw materials for the manufacture of filter bags are packed in 2 g each in a special heat-sealing porous paper on an ARIZ apparatus. To prepare dry extracts and syrups for special purposes, the collection is extracted under vacuum (-0.8 atm) at a temperature of 65 ± 5 ° C for 2 hours. A syrup is prepared by saturating the extract with dissolved sugar to a concentration of 60-64%, then the syrup is bottled and pasteurized. To obtain a dry extract, a 5% liquid extract is first concentrated using the UMK installation (membrane concentration installation) to a concentration of 18-20%, and then the concentrate is spray dried to 95-97% dry matter and hermetically packed in 1000 g for subsequent industrial processing. The solid form (tablets) is prepared from the dry extract and excipients on tablet machines.

To prepare an aqueous extraction of 4.0 g of the collection, pour 200 ml of purified room temperature water, insist in an infundira apparatus for 15 minutes, then cool at room temperature for 45 minutes; filter, squeeze the plant material and add water to the required extraction volume. When preparing an infusion of filter bags (2 g), it is necessary to place the filter bag in a cup, pour 200 ml of boiling water, close the lid and let it brew for 10-15 minutes. Dry extract is intended for further industrial processing. A drink is prepared from special-purpose syrup by adding 20-30 ml of syrup to boiled water or tea. Dosage of the tablet form 0.1 g of dry extract in a tablet.

The action of the collection was investigated on the analgesic (analgesic) effect on white non-inbred rats on the model of “acetic cramps”, which were caused by a single intraperitoneal injection of 1 ml of 1% acetic acid, and the time of their onset was recorded for 15 minutes. As a comparison drug, analgin was administered intragastrically 50 mg / kg. In the control group, the pain syndrome manifested itself after 4.5 minutes, the collection delayed the manifestation of the pain syndrome for 7.8 minutes, and analgin 9.8 minutes. Thus, the analgesic effect of the collection is comparable to the action of analgin (table. 1).

The anti-inflammatory activity of the collection was investigated for decongestion in the development of carrageenin inflammation, which is recorded by the magnitude of the formed edema in white non-inbred rats (Table 2). Comparison drug ortofen reduced exudation by 63.7%, collection by 23.9% of the control.

Membrane-protective activity was observed in the model of acute carbon tetrachloride poisoning. In the integrated test, the microviscosity of the membranes was assessed by the mobility of the fluorescence probe of pyrene in the erythrocyte membranes (Table 3). The structure of biomembranes in the pathogenesis of most pathological conditions is violated due to the intensification of lipid peroxidation, during which hydroperoxide groups are formed in hydrophobic fatty acid lipid residues. The interaction of these groups with other polar structures of biomembranes leads to an increase in microviscosity of cell and subcellular membranes, which, as a result, leads to disruption of intracellular metabolism. As can be seen from table 3, the collection in its action occupied an intermediate position between the control (intact animals) and untreated. Thus, the collection has a certain membrane protective effect.

Hepatoprotective activity of the collection was evaluated in 2 models:

Toxic hepatitis was caused by subcutaneous administration of 50% carbon tetrachloride daily for 4 days. The collection was administered within 4 days in 15 minutes and 2 hours after poisoning. As a comparison drug used hepatoprotector "Silibor" at a dose of 5 mg / kg. In the blood serum, the activity of alanine aminotransferase was determined, aspartate minotransferase whose increased level indicates damage to the hepatocyte membranes, and a thymol test was performed. Collection treatment led to an improvement in biochemical parameters and is comparable to the Silibor comparison drug (Table 4).

In untreated animals with toxic hepatitis, AlAT activity increased by 15.1 times, AsAT activity - by 10.2 times, thymol test increased by 7 times. Treatment with collection and Silibor reduced AlAT activity, respectively, 10.56 and 3.9 times, AsAT activity 5.2 and 2.1 times, reduced the severity of the thymol test, the values of which exceeded normal values, by 3.6 and 1.7 times, respectively.

High values of the thymol test indicate impaired functioning of hepatocytes (liver parenchyma). Elevated levels of AlAT and AsAT indicate damage to the liver cells. The pharmacological effect of the collection, leading to an improvement in biochemical parameters comparable with Silibor, allows us to conclude that hepatoprotective activity is present.

In the second model, acute toxic hepatitis was caused by an industrial toxicant from the group of hydrazine derivatives. The drugs “Karsil”, “Heptral” and “Essential” served as comparison drugs. These preparations and collection were administered to animals for. day and an hour before the hepatotoxicant. The survival of animals was recorded by day (up to 14 days). Under the action of the LD ₅₀ toxicant on day 4, the survival rate of white mice was 100% with the use of the drug Karsil, collection 83%, Heptral 66%, Essential 50% (Table 5). As can be seen from table 5, the collection exceeded the well-known pharmacopoeial hepatoprotectors, Heptral and Essential, and was close to the action of Karsila.

Under more “harsh” conditions (“2LD ₅₀ toxicants) for 4 days the survival rate was“ Karsil ”- 53%, collection - 46% (Table 6).

Thus, the collection has hepatoprotective activity.

Antioxidant activity of the collection was evaluated by chemiluminescence in experiments in vitro and in vivo (Farkhutdinov, Likhovsky, 1995). At a dose of 0.1 mg / ml, the collection inhibited more than 50% of free radical reactions in the system for the generation of reactive oxygen species and in the lipid peroxidation system at a dose of 1 mg / ml. On the glow of whole blood, caused mainly by neutrophilic granulocytes, the collection had a stimulating effect. The generation of biooxidants increased by 25.9% (Table 7). It is known that luminol-dependent neutrophil chemiluminescence is closely related to the myeloperoxidase system and determines bactericidal activity (Horan et al., 1982). The synthetic antioxidant Mexidol, on the contrary, inhibits the luminescence of phagocytes.

The collection was also used in complex therapy with drugs in the rehabilitation of persons in contact with occupational hazards. So for a group of 34 people in the functional state of the autonomic nervous system, there was a predominance of vagotonic signs in the initial vegetative tone, an impaired microcirculation of an extravascular nature. Spontaneous and stimulated chemiluminescence levels of whole blood were also reduced.

Table 1.
Analgesic action of the collection Name of fee Time of onset of pain, min The number of cramps Collection 7.8 ± 0.6 * 11.0 ± 1.4 * “Analgin” (comparison drug) 9.8 ± 0.8 * 10.7 ± 0.9 * The control 4,5 ± 0,3 32.7 ± 3.1 * Differences with the control group are statistically significant. Table 2.
Antiexidative effect of collection on a model of carrageenin inflammation. Name of fee The magnitude of the edema after 3 hours,% The magnitude of the edema after 24 hours,% Collection 48.5 ± 6.6 38.6 ± 4.8 * “Ortofen” (comparison drug) 19.8 ± 0.9 * 22.7 ± 1.0 * The control 54.6 ± 3.7 50.7 ± 3.9 * Differences with the control group are statistically significant.

Table 3.
The effect of drugs on the microviscosity characteristics of erythrocyte membranes in rats poisoned by carbon tetrachloride Group F ₄₀₀ F ₄₇₅ K _Exim (F ₄₇₅ / F ₄₀₀ ) The control 68.1 ± 4.7 37.3 ± 3.0 0.55 □ Untreated 88.7 ± 5.3 30.2 ± 2.1 0.34 * Collection 80.1 ± 4.0 31.9 ± 2.6 0.40 * * Differences with the control group are statistically significant.
□ Differences with the untreated group are statistically significant. Table 4.
Hepatoprotective activity collection (1 model) Group name The activity of AlAT, μm / h · ml The activity of AsAT, μm / h · ml Thymol test, rel. units The control 0.24 ± 0.03 * 0.33 ± 0.02 * 2.1 ± 0.01 * Collection 2.51 ± 0.24 * 1.72 ± 0.32 * 7.6 ± 0.6 * Silibor (comparison drug) 0.93 ± 0.22 * 0.68 ± 0.40 * 3.6 ± 0.4 * Control (untreated) 3.62 ± 0.29 3.36 ± 0.35 14.6 ± 0.1 * Differences with the control group are statistically significant.

Table 5.
The effect of collection on the survival of white mice in acute toxicosis (including hepatosis) in case of poisoning at a dose of LD ₅₀ ,% protection A drug 1st day 4th day Qualitative assessment of the drug Karsil 100 100 Protective Collection 83 83 Activity: expressed Heptral 66.6 66.6 moderate Essentiale fifty fifty not effective The control fifty 33 Table 6
The effect of collection on the survival of white mice with 2LD ₅₀ toxicants,% A drug 1st day 4th day Karsil 60 53 Collection 53 46 The control 0 0

Table 7.
The effect of different concentrations of collection on the chemiluminescence of model systems (in cu) Fitosbor Concentration, mg / ml ROS generating system LPO Trigger System Whole Blood Phagocyte System SS % of control SS % of control SS % of control The control 0 14.08 ± 0.03 100.00 34.91 ± 1.40 100.00 100.00 0.01 8.7 ± 0.3 62.42 * 30.65 ± 1.30 87.79 * Collection 0.1 8.62 ± 0.1 61.35 * 28.20 + 0.90 80.77 * 322.8 ± 11.1 125.89 * 1,0 6.77 ± 0.04 48.08 * 9.74 ± 0.60 27.90 * * P <0.05.

At the beginning of treatment, euphillin was prescribed in tablets of 0.15 for 10 days to remove perivascular edema, then 5 ml of 20% solution intramuscularly for 10 days for piracetam, then in 0.4-0.8 capsules 2 times a day for up to 1 month. Subsequently, a collection of 2% aqueous infusion of 200-300 ml per day was prescribed for 20 days.

After the first course of treatment, consisting of prescribed medications, there was an improvement in microcirculation, a tendency toward normalization of blood chemiluminescence indices, more pronounced in relation to indices of spontaneous luminescence. After the course with the use of collection, these changes grew, the effect of normalizing the functional reserve of phagocytic blood cells was more pronounced - the difference between the light sum of the stimulated and spontaneous chemiluminescence of whole blood. 90.3% of patients showed this trend. Immunological parameters also improved - the number of T-lymphocytes, including helper inducers, increased, the immunoregulatory index changed due to a decrease in the content of suppressor-cytotoxic cells.

In general, the use of collection in complex therapy with drugs had a positive effect on microcirculation, the central nervous system, and free radical oxidation. The results allow us to recommend a fee for the treatment of persons in contact with occupational hazards, since due to their negative impact on the body, most workers are in a non-optimal functional state, which can be regarded as a pre-illness.

Thus, the proposed collection can be used in the complex therapy of diseases of the liver and biliary tract, as well as the prevention of chronic intoxication associated with industrial (industrial) and domestic toxic effects.

Claims (5)

1. An agent for the treatment and prevention of diseases of the liver and biliary tract during chronic intoxications associated with industrial (technogenic) and domestic toxic effects, containing milk thistle fruits, characterized in that it additionally contains immortelle flowers, bird of the highlander (knotweed), oregano grass , yarrow grass, motherwort grass, rose hips, flax seeds, alder fruit, chaga, in the following ratio, wt.%: Helichrysum flowers 1.9 Highlander (knotweed) grass 3.2 Oregano grass 6.3 Yarrow Grass 12.6 Motherwort grass 3.2 Thistle fruit 12.6 Rose hips 19,0 Flax Seeds 3.2 Fertility alder 19.0 Chaga 19.0 2. The tool according to claim 1, characterized in that it is made in the form of a solid form (tablets). 3. The tool according to claim 1, characterized in that it is made in the form of a syrup. 4. The tool according to claim 1, characterized in that it is crushed and packaged in filter bags. 5. The tool according to claim 1, characterized in that it is made in the form of a dry extract for subsequent industrial processing.