RU2393721C2 - Agent and alcohol-free drink for prophylactics of consequences and reduction of manifestations of acute alcohol intoxication - Google Patents

Abstract

FIELD: food industry.

SUBSTANCE: method for prophylactics of consequences and reduction of acute alcohol intoxication manifestations contains biologically active compounds of dry extract of haws. The latter includes procyanidins (from monomers to hexamers with average extent of polymerisation from 1.1 to 5.5) from 1.0-50.0 mg/g of extract dry weight equivalent to cyanidin chloride), epicatechins, chlorogenic acid and flavonoids, represented by hyperoside, rutin, quercitin, glycosides of vitexin, vitexin, isovitexin, orientin, isoorientin, apigenin, with total concentration of phenol compounds of at least 10 mg/g of extarct dry weight equivalent to gallic acid. Alcohol-free drink for prophylactics of consequences and reduction of unfavorable manifestations of acute alcohol intoxication contains above-specified dry extract of haws in concentration from 1.0 to 60.0% as an active substance. It makes it possible to increase latent period of narcotic dream and to reduce its duration.

EFFECT: drink with application of this agent weakens intoxication specific for usual taken dose of vodka and at the same time preserves invigorating feeling.

5 cl, 13 tbl, 7 ex

Description

The invention relates to the field of creating funds and soft drinks based on natural raw materials with prophylactic and therapeutic properties, sobering up effect on alcoholic intoxication and reducing the concentration of exogenous ethanol in the blood.

The state of intoxication is a factor of increased mortality, which causes a whole range of medical and social problems. According to expert estimates, alcohol is a direct or indirect cause of the order of half a million deaths of Russians annually [Alcohol catastrophe and the possibility of state policy in overcoming alcoholic deaths in Russia / Otv. ed. D.A. Khalturina. A.V. Korotaev. M .: LENAND, 2008. - 376 p.].

The dominant idea of the nature of mental and somatic disorders observed with alcohol abuse is based on the postulate of a direct causal relationship between these disorders and the ethanol content in human tissues and biological fluids.

One of the ways to prevent the consequences and reduce the manifestations of acute alcohol intoxication, in particular, intoxication, is to use foods that reduce the content of exogenous ethanol by slowing the evacuation of stomach contents or increasing the efficiency of the primary metabolism of ethanol (First Pass Metabolism, FPM) in the gastrointestinal tract . A decrease in the manifestations of acute alcohol intoxication can also occur due to increased hepatic blood flow, induction of the synthesis of ethanol oxidation enzymes in the liver and / or an increase in the rate of NADH reoxidation.

The traditional way to achieve this effect at the household level is to eat food (snacks) before and / or while taking alcoholic beverages. It is generally accepted that the presence of food in the stomach only slows the flow of alcohol into the intestines, to the place of main absorption, which determines the milder character of intoxication. However, the presence of food in the stomach not only slows the evacuation and absorption of alcohol, which leads to an increase in the latency of reaching a peak blood alcohol concentration (V _max ), but is also accompanied by a significant decrease in the integral blood alcohol content (AUC), where AUC (Area Under Curve) - area under the ethanol elimination curve.

The decrease in ethanol AUC when food is in the stomach can be explained by both stimulation of alcohol metabolism in the liver and FPM activation, which reduces the bioavailability of alcohol when administered orally. The participation of both processes seems most probable [Rozhanets V.V. and Necessary V.P. Primary ethanol metabolism in the gastrointestinal tract // Issues of addiction medicine - 2007. - No. 5-6. - S. 37-42].

In addition to food products consumed in quantities that have significant nutritional value, low-calorie plant extracts can have a significant effect on the rate of elimination of ethanol when they are consumed in quantities that are not of nutritional value or at a dose at which they are unable to serve as food products.

It was shown that aloe leaf extract when administered orally to rats 30 minutes before ethanol was administered was able to accelerate its elimination [Sakai K., Saitoh Y., Ikawa C. et al. Effect of water extracts of aloe and some herbs in decreasing blood ethanol concentration in rats. II. // Chem. Pharm. Bull. (Tokyo). - 1989. Vol. 37 (1). - P.155-159].

Known means for the prevention and reduction of adverse manifestations of acute alcohol intoxication based on the extract of seeds and / or inflorescences of plants of the family Brassicaceae. One form of the proposed drug (lyophilized extract) in doses of 200-800 mg / kg when administered orally to rats reduces the content of exogenous ethanol in the blood and has a sobering effect on animals [Application 2004119533/15, 06/29/2004].

It was found that decoction of St. John's wort herb is capable of exerting a sobering effect during alcohol intoxication and reduce the time of regression of withdrawal symptoms [Auth. testimonial. USSR 1795581, A61K 35/78, 1990].

Known tool based on extracts of grape ridges, St. John's wort and rose hips, reducing the toxic effect of alcohol in laboratory animals and in healthy subjects [Application 2003116625/15, 2003.06.05].

Known means to reduce the effect of acute alcohol intoxication and post-toxic alcohol syndrome based on succinic and fumaric acids, fructose, St. John's wort herb extract, sources of potassium and magnesium ions [Application WO 2004RU00517 20041223]. The use of a biologically active food supplement called "Antip Green", corresponding to the proposed remedy, reduces the severity of symptoms of acute alcohol intoxication and post-toxicity [Nuzhny VP, Pometov Yu.D., Martyushov AN et al. Investigation of the effect of the biologically active food supplement “Antip green” (RU21 green) on the severity and structure of manifestations of alcohol intoxication and post-toxicity in an experiment in healthy volunteers // Narcology. - 2005. - No. 8. - S. 39-47].

A chewing gum containing a kudzu root juice concentrate has been proposed as an anti-alcoholic [Application CN 20041054141 20040831].

A well-known drink with a sobering and hepatoprotective effect, made from the flowers of chrysanthemum, roses, Japanese sophora and kudzu as the main components. The secondary components of this drink are the leaves of Japanese medlar, mulberry, basil and mint; additional components are lotus and bamboo leaves [Application CN 19941000339 19940115].

A sobering carambola drink is known, consisting of the juice of the fruit of the Karambola tree (Averrhoa carambola) with the addition of several plants, including the five-leafed Gynostemma (Gynostemma pentaphyllum), kudzu flowers and a number of components [Application CN 20001026712 20001127].

A sobering composition in the form of a dry powder is described, consisting of six medicinal components accepted in Chinese medicine: kudzu roots, bitter pattra fruit, fungus mushroom (Poria cocos), magnolia vine fruits, green tea and cloves [Application CN 20021054140 20021226].

A sobering tea with anabolic action based on the roots of kudzu, one of the varieties of cardamom, Chinese oolong tea and other components has been proposed [Application CN 19981013780 19980224].

A composition has been patented that has a sobering and hepatoprotective effect, consisting of extractive compounds of soybean, dereza fruit (Lycium), plantain rhyme (Alisma plantago-aquatica), L-cysteine, vitamins and other components [Application CN 20031022873 20030508].

A patent application for a sobering agent is published, which includes one of the varieties of tea, lemon, red orange, kudzu and licorice roots with taurine and honey [Application CN 20031008564 20030326].

A sobering drink is proposed that has both tonic and hypnotic effects based on rhodiola and honey [Application CN 19991009283 19990625].

Granules having a sobering and hepatoprotective effect are described, made on the basis of extracts from fungi of the genus Hericium, cardamom, grapefruit, candy tree (Hovenia acerba), kudzu flowers [Application CN 19941013986 19941111].

A sobering agent has been proposed that includes extracts of Chinese plants Tupistra chinensis and plants of the family Balanophoraceae parasitizing on tree roots [Application CN 20061019115 20060519].

Describes a sobering agent based on fresh pear juice with the addition of sorbitol, citric acid and honey [Application CN 2006108382620060605].

A sobering and hepatoprotective agent based on peptides of soybean extract, panaxosides of ginseng leaves, green tea polyphenols, amino acids and vitamins has been proposed [Application CN 20051077612 20050621].

Describes a sobering and hepatoprotective agent based on extracts of bitter orange and grape seeds subjected to hard radiation using Co ⁶⁰ [Application CN 20041046032 20040602].

A sobering agent (also effective in diseases of the upper respiratory tract) based on an extract of iris rhizomes has been proposed [Application CN 20041022293 20040406].

Claimed sobering, hepatoprotective and restorative agent obtained by deep extraction of tinder fungus Glossy Ganoderma Mask [Application CN 20031113 316 20031110].

A commercially available Security Feel Better drink is known containing artichoke extract (Cynara scolymus), ascorbic acid and fructose. In the Russian Federation, an identical drink is also known as Vik's Wonder®. According to the manufacturers, the use of 30 ml of this product before taking alcoholic beverages increases the rate of ethanol oxidation by 2.5-6 times and weakens the manifestations of post-toxic alcohol syndrome (hangover). However, information on the ability of artichoke extracts to influence the metabolism of ethanol is not available in the scientific literature. A randomized, placebo-controlled trial of the action of a standardized artichoke extract did not reveal its effect on the severity of symptoms of an alcoholic hangover [Pittler MN, White A.R., Stevinson C. et al. Effectiveness of artichoke extract in preventing alcohol-induced hangovers: a randomized controlled trial. // CMAJ. - 2003 .-- V.169 (12). - P.1269-1273]. Thus, the information on the sobering effect of drinks consisting of artichoke extracts given in advertising texts is not true.

Several patent applications have been published for compositions with a sobering effect, containing extracts of hawthorn fruit.

Known sobering and hepatoprotective drink containing extracts of flowers and roots of kudzu, black plum, ginseng, dried peel of mandarin, fruits of the tropical plant Longan (Euphoria longan), raisins, chrysanthemum, fruits of the snowberry or barbary dereza (Lycium barbarum), root gingerbread , or medicinal (Polygonatum odoratum), figs, Chinese dates and pumpkins [Application CN 19951019327 19951123].

Describes a drink that reduces alcohol intoxication, the components of which are 23 traditional Chinese medicinal objects, including kudzu roots (pueraria), hawthorn fruits, sweet potato tubs, hyacinth beans, oyster shells and other components [Application CN 20021010916 20020228].

A carbonated drink having anti-alcoholic and health-improving properties is proposed, which includes juice of kudzu roots, cardamom pods, aloe leaves, fruits of hawthorn and watermelon, cane, pineapple and other components [Application CN 20031052822 20030822].

A drink based on the fungus mushrooms of the genus Ganoderma, tea, kudzu flowers, tangerine peel and hawthorn fruit is patented. According to the authors, its use before drinking alcohol increases the tolerance to the acute toxic effect of alcohol, and use after alcohol excesses avoids hiccups, suppresses the vomiting reflex and normalizes digestive function [Application CN 20001031281 20001215].

Formally, the closest to the present invention relates to a herbal sober action based on an extract from the aboveground parts of elecampane, which reduces the content of exogenous ethanol in the blood and reduces the severity of symptoms of intoxication [Application 2003116624/15, 05/06/2003; WO 2004RU00213 20040603; RF patent No. 2229304. Registered May 27, 2004.].

Known plant composition corresponding to the claimed tool, consisting of equal parts of dry extracts of flowers of Elecampane high and the fruits of the blood-red hawthorn called "Depromil". In a randomized, placebo-controlled study conducted on 126 patients with stage II alcoholism who were admitted to a narcological hospital while intoxicated with mild to moderate severity, this phytocomposite, used against the background of standardized detoxification therapy, has the ability to provide a sobering effect, reducing the severity of manifestations alcohol intoxication. [Paveliev E.V., Garev F.V., Rozhanets V.V. et al. Phytocomposition "Depromil": a study of the effect on elimination of alcohol and manifestations of alcohol intoxication in patients with alcoholism // Narcology. - 2008. - No. 2 (74). - S. 47-55.].

Elecampane flowers have the ability to have a luteinizing and abortive effect. In a number of countries in the Middle East, decoctions of elecampane flowers are traditionally used as an effective abortive agent [Al-Dissi N.M., Salhab A.S., Al-Hajj H.A. Effects of lnula viscosa leaf extracts on abortion and implantation in rats. // J. Ethnopharmacol. - 2001 .-- Vol.77 (1). -P.117-121.]. This significantly limits the use of this plant object for food purposes and serves as an objective obstacle to the use of the Depromil phytocomposition as a food product. That is why the herbal composition “Depromil” is intended only for detoxification in case of alcohol poisoning in medical hospitals or medical detoxification centers and cannot be considered as a food product.

Hawthorn fruits are also a raw material for the production of drugs used as antiarrhythmic and cardiotonic agents for functional disorders of cardiac activity, heart weakness and initial forms of hypertension [Pittler MH, Guo R., Ernst E. Hawthorn extract for treating chronic heart failure // Cochrane Database Syst. Rev. - 2008. - Jan 23; (1): CD005312].

Currently, several hundred species of hawthorn are known. Of these, the Russian Pharmacopoeia and the State Pharmacopoeia of the USSR from the 1st to the 11th editions include the following species as equivalent: 1) blood red or Siberian hawthorn - Crataegus sanguinea Pall., 2) smoothed hawthorn - C. laevigata Poir. (prickly - S. oxyacantha sensu Pojark.), 3) Korolkov hawthorn - S. korolkovii L., Henry (Altai - C. altaica (Lond.) Lange)., 4) yellow hawthorn - C. chlorocarpa Lenne., 5) daursky hawthorn - S. dahurica Koehne ex Schneid., 6) single-hawthorn hawthorn - S. monogina Jacq., 7) German hawthorn - C. alemanniensis Cin., 8) five-hawthorn hawthorn - C. pentagyna Waldst. et Kit., 9) eastern Baltic hawthorn - C. orientobaltica Cin., 10) bent hawthorn - C. curvisepala Lindm., 11) Kurzeme hawthorn - C. x curonica Cin., 12) Daugava hawthorn - C. x dunensis Cin. ., hawthorn pinnatifolia or Chinese C. pinnatifida bunge. [MH. State Pharmacopoeia of the USSR XI edition. Issue 2. General methods of analysis. Plant materials (as of October 20, 2006)].

The fruits of various types of hawthorn contain up to 15 different polyphenols, which make up about 20% of their dry weight. These compounds are represented by procyanidins (from monomers to hexamers), epicatechins, chlorogenic acid and flavonoids represented by hyperoside, rutin, quercetin, vitexin glycosides, vitexin, isovitexin, orient, isoorientin, apigenin, etc.

It was shown that it is these compounds that are included in extracts of hawthorn fruits and have high antioxidant activity that provide their cardiotonic, anti-ischemic, anti-stenocardial and hypolipidemic effect, as well as their activity as inhibitors of the angiotensin-converting enzyme [Bahorun T., Gressier B., Trotin F. et al. Oxygen species scavenging activity of phenolic extracts from hawthorn fresh plant organs and pharmaceutical preparations. // Arzneimittclforschung. - 1996.- V. 46 (11). - P.1086-1089]; [LacailIe-Dubois., Franck U., Wagner H. Search for potential angiotensin converting enzyme (ACE) -inhibitors from plants. // Phytomedicine. - 2001 .-- V.8 (1). - P.47-52]; [Cui T., Nakamura K., Tian S. et al. Polyphenolic content and physiological activities of Chinese hawthorn extracts // Biosci. Biotechno. Biochem. - 2006 - Vol.70 (12). - P.2948-2956].

In an experimental model of myocardial infarction, hawthorn fruit extracts exhibit hepatoprotective effects [Thirupurasundari C. J., Jayalakshmi R., Niranjali Devaraj S. Liver architecture maintenance by tincture of Crataegus against isoproterenol-induced myocardially infarcted rats // J. Med. Food - 2005 .-- Vol.8 (3). - P. 400-404].

The principal pharmacological equivalence of aqueous-alcoholic and aqueous extracts of hawthorn has been shown [Vierling W., Brand N., Gaedcke F. et al. Investigation of the pharmaceutical and pharmacological equivalence of different Hawthorn extracts // Phytomedicine. - 2003. Vol.10 (1). - P.8-16].

It is significant that all previously proposed products containing hawthorn fruit extract, intended to weaken one of the primary manifestations of acute alcohol intoxication (namely, to sober up), additionally contain medicinal plants and / or other ingredients in their composition. In addition to the flowers of elecampane, these components are represented by the flowers and rhizomes of kudzu, barbarian dereza fruits, rhizomes bought fragrant or medicinal, aloe leaves, fungi, fungus genus Ganoderma and shell oysters.

So, the roots and other parts of the kudzu plant (Pueraria), which are components of all the claimed sobering agents (excluding the product based on the extract from the aboveground parts of elecampane), contain more than a dozen phytoestrogens, which significantly affect the hormonal status of animals and humans. The severity of this pharmacological effect of kudzu allows us to consider this plant in a number of other herbal means of regulating fertility in humans [Kamboj V.P., Dhawan B.N. Research on plants for fertility regulation in India // J. Ethnopharmacol. - 1982. - Vol.6 (2). - P.191-226.]. Recent studies have shown that chronic administration of kudzu extract in non-toxic doses can significantly reduce the likelihood of conception in mice, significantly reducing the level of luteinizing and follicle-stimulating hormones in the blood of animals [Jaroenpom S., Malaivijitnond S., Wattanasirmkit K. et al. Assessment of fertility and reproductive toxicity in adult female mice after long-term exposure to Pueraria mirifica herb // J. Reprod. Dev. - 2007 .-- Vol. 53 (5). - P.995-1005]. These properties of kudzu indicate the unsafe use of this plant as a food product.

Aloe leaf juice can also not be considered as a food product due to the well-documented, lactating properties known for millennia.

Hawthorn fruits in the Russian Federation are a food product used in the manufacture of confectionery, dairy products, soft drinks and alcoholic beverages and do not have the above disadvantages.

The objective of the present invention is to achieve a sobering effect by increasing the rate of elimination of exogenous ethanol when using a herbal product, which is a food product in the Russian Federation.

This object is achieved by the fact that the proposed tool for the prevention of consequences and reduce the adverse manifestations of acute alcohol intoxication, containing hawthorn fruit extract, including procyanidins (from monomers to hexamers with an average degree of polymerization from 1.1 to 5.5) from 1.0-50 , 0 mg / g dry weight of the extract in terms of cyanidin chloride), epicatechins, chlorogenic acid and flavonoids represented by hyperoside, rutin, quercetin glycosides of vitexin, vitexin, isovitexin, orient, iso-orientation Mr., Apigeninom, with a total concentration of phenolic compounds of at least 10 mg / g dry weight of the extract in terms of gallic acid.

The product contains extracts of the fruits of pharmacopeia hawthorn species.

The tool can be made in the form of a solution, suspension, soluble powder, as well as soluble (including effervescent) tablets.

The tool may contain excipients, carriers and / or excipients.

A soft drink is also proposed to prevent the consequences and reduce the adverse manifestations of acute alcohol intoxication, characterized in that it contains as an active substance a dry extract of hawthorn fruit in a concentration of from 1.0 to 60.0%.

The technical result consists in the fact that when using an agent based on a dry extract of hawthorn, including procyanidins (from monomers to hexamers with an average degree of polymerization from 1.1 to 5.5) from 1.0-50.0 mg / g dry weight of the extract in terms of cyanidin chloride), epicatechins, chlorogenic acid and flavonoids represented by hyperoside, rutin, quercetin, vitexin glycosides, vitexin, isovitexin, orient, isoorientin, apigenin, with a total concentration of phenolic compounds of at least 10 mg / g dry weight extract and in terms of gallic acid, as well as a non-alcoholic drink with this extract in a concentration of from 1.0 to 60.0%, the adverse effects of acute alcohol intoxication on a large number of people taking alcohol are significantly reduced. The product and the drink can be used for prophylactic and therapeutic purposes.

The tool is used before drinking alcohol, during their use or after an alcoholic excess.

The advantage achieved by using the present invention is to achieve the claimed effect when using only products and components authorized in the Russian Federation for use as components of soft drinks.

The effectiveness of the proposed tool that reduces the adverse effects of acute alcohol intoxication is confirmed, in particular, by the following examples, which only illustrate the feasibility of the invention and its advantages and cannot be construed as limiting.

Example 1. The study of the effect of water extracts from the fruits of different types of hawthorn on the acute toxicity (narcotic effect) of ethyl alcohol.

Four types of hawthorn are most widely represented in the Russian Federation: b. blood red - C. sanguinea Pall .; b. prickly - S. oxyacantha sensu Pojark .; b. monoecious - C. monogyna Jacg. and b. fivefold - S. pentagyna Waldst. et Kit.

For a comparative assessment of the desired biological activity in these experiments, the fruits of the hawthorn of the four above types were used, of which aqueous extracts were prepared under laboratory conditions (freshly prepared water infusions with a solids content of 12 mg / ml).

Male CBA / lac mice weighing 20-24 g were injected intragastrically with liquid extracts of different types of hawthorn fruit at a dose of 200 mg / kg (in terms of solids). The control group mice were injected with an equal volume of water. The amount of injected fluid did not exceed 20 ml / kg. After 20 minutes, the mice of the control and experimental groups were injected intraperitoneally with ethanol in the form of 20%, w / v, solution at a dose of 4 g / kg. The latent period of narcotic sleep was recorded (the time from the moment ethanol was introduced until the animals adopted a lateral position, s) and the duration of narcotic sleep (time spent in the lateral position, min). The results of the experiment are presented in table 1.

Table 1. The effect of aqueous extracts of different species of hawthorn fruit on the latent period and duration of narcotic sleep caused by ethanol (M ± S.D.) Groups of animals (n = number of mice in the group) Latent period of narcotic sleep, s Duration of drug sleep, min Control (n 14) 89 ± 16 54 ± 18 hawthorn blood red (n 14) 116 ± 21 * 35 ± 16 * prickly hawthorn (n 14) 119 ± 24 * 38 ± 19 * single-haw hawthorn 115 ± 25 * 36 ± 18 * (n 13) pentacarpal hawthorn (n 13) 114 ± 22 * 39 ± 20 * Note: * - p <0.05 compared with control

From the table it follows that extracts of hawthorn fruit of all tested species increase the latent period of narcotic sleep caused by ethanol and reduce the duration of narcotic sleep in mice.

All subsequent studies were carried out using blood-red hawthorn, taking into account its widest raw material base.

Example 2. The study of the effect of solutions of dry aqueous and aqueous-alcoholic extracts of the fruit of the hawthorn blood-red on the acute toxicity (narcotic effect) of ethyl alcohol in mice.

Water and water-alcohol extraction of the blood-red hawthorn fruit was carried out under laboratory conditions by the method of repercolation. The extracts were dried at a temperature of 60 ° C. The content of phenolic compounds in the aqueous extract, measured according to the method of Folin-Ciokalteu, was 106.7 mg / g in terms of gallic acid. The content of procyanidins in the aqueous extract, measured according to the method recommended by the European Pharmacopoeia 5.0 in monograph 01/2005: 1220, was 10.1 mg / g in terms of cyanidin chloride. For the water-alcohol extract, these values were 143.2 mg / g and 11.3 mg / g, respectively. Before the study, the dry extracts were dissolved in water (12 mg / ml).

Male CBA / lac mice weighing 20-24 g were injected intragastrically with extract solutions at doses of 100 mg / kg and 200 mg / kg (in terms of solids). The mice of the control group were injected with an equal amount of water. The amount of injected fluid did not exceed 20 ml / kg. After 20 minutes, the mice of the control and experimental groups were injected intraperitoneally with ethanol in the form of 20%, w / v, solution at a dose of 4 g / kg. The latent period of narcotic sleep was recorded (the time from the moment ethanol was introduced until the animals adopted a lateral position, s) and the duration of narcotic sleep (time spent in the lateral position, min). The experimental results are presented in table 2.

Table 2. The effect of aqueous and aqueous-alcoholic extracts of the blood-red hawthorn fruit on the latent period and the duration of narcotic drug-induced sleep (M ± S.D.) Groups of animals (n is the number of mice in the group) Latent period of narcotic sleep, s Duration of drug sleep, min Control (n 14) 89 ± 16 54 ± 18 Water extract 100 mg / kg (n 14) 103 ± 29 * 44 ± 20 * Water extract 200 mg / kg (n 14) 112 ± 24 * 39 ± 18 * Water-alcohol extract 100 mg / kg (n 14) 98 ± 23 * 48 ± 14 * Water-alcohol extract 200 mg / kg (n 14) 105 ± 25 * 40 ± 20 * Note: * - p <0.05 compared with control

From the table it follows that aqueous solutions of aqueous and aqueous-alcoholic extracts of the blood-red hawthorn fruit exhibit a pronounced ability to dose-dependently attenuate the acute toxic (narcotic) effect of ethyl alcohol in mice.

All of the following examples illustrate studies that were carried out using freshly prepared water extracts (tinctures) of the blood-red hawthorn fruit.

Example 3. The study of the effect of the extract of hawthorn fruit on the dynamics of the narcotic action of ethyl alcohol in an experiment on rats.

Male Wistar rats weighing 220-260 g were injected intragastrically with an extract of hawthorn fruit (freshly prepared aqueous extract with a solids content of 12 mg / ml) at doses of 100 and 200 mg / kg (in terms of solids). The rats in the control group were injected with an equal amount of water. The volume of injected fluid did not exceed 15 ml / kg. 30 minutes later rats of the control and experimental groups were injected intragastrically with ethanol in the form of 30%, w / v, solution at a dose of 4 g / kg. The condition of the animals was evaluated hourly for 10 hours and expressed it in points using the developed ranking scale for the manifestations of alcohol intoxication. The integral severity of alcohol intoxication was assessed by the total score for the entire observation period [Nuzhny V.P. et al. The effect of fusel oil components and the ether-aldehyde fraction on the acute toxicity and narcotic effects of ethyl alcohol. - Toxicol. Herald. - 1999. - No. 2. - C.2-8]. The results of the study are presented in table 3.

Table 3. The effect of hawthorn fruit extract on the dynamics of the narcotic effect of ethanol, expressed in points (M ± S.D.) The time after the introduction of ethanol, hours Groups of animals (n-number of rats in the group) Control (n 12) Hawthorn, 100 mg / kg (n 12) Hawthorn, 200 mg / kg (n 12) one 4,5 ± 0,5 4.2 ± 0.4 4.2 ± 0.6 2 4.4 ± 0.5 4.1 ± 0.5 4.0 ± 0.5 3 4.3 ± 0.4 3.9 ± 0.4 3.7 ± 0.4 * four 4.1 ± 0.4 3.7 ± 0.2 * 3.4 ± 0.3 * 5 3.7 ± 0.2 3.4 ± 0.3 * 3.0 ± 0.3 * 6 3.3 ± 0.3 3.0 ± 0.3 * 2.7 ± 0.2 * 7 2.6 ± 0.2 2.3 ± 0.2 * 2.0 ± 0.3 * 8 2.2 ± 0.3 1.8 ± 0.3 * 1.5 ± 0.4 * 9 1.9 ± 0.4 1.4 ± 0.7 0.8 ± 0.5 * 10 1.2 ± 0.5 0.9 ± 0.6 0.2 ± 0.5 * Total points 32.2 ± 2.4 28.7 ± 2.6 * 25.2 ± 2.5 * Note: * - p <0.05 compared with control

From the table it follows that the use of extract of hawthorn fruit in doses of 100 and 200 mg / kg dose-dependently accelerates the exit of animals from intoxication, weakening the severity of alcohol intoxication (total points) by 10.9% and 21.3%, respectively.

Example 4. The study of the effect of the extract of the fruit of the hawthorn blood red on acute toxicity (lethal effect) of ethyl alcohol in mice.

Male CBA / lac mice weighing 20-24 g (63 individuals) were administered the intragastrically proposed drug in the form of a solution of extracts of hawthorn fruit (with a solids content of 12 mg / ml) at a dose of 200 mg / kg (in terms of solids) . The mice of the control group were injected with an equal amount of water. The volume of injected fluid did not exceed 20 ml / kg. After 20 minutes, the mice of the control and experimental groups were injected intraperitoneally with ethanol in the form of 30%, w / v, solution. For injections of ethanol solution, syringes with a division value of 0.02 ml were used. The ethanol dose range was 6.0-9.2 g / kg ethanol in increments of 0.4 g / kg. The number of animals in each group is 7. Registration of the number of surviving animals was carried out for 3 days after the introduction of ethanol. Based on the data obtained, LD ₁₆ , LD _50, and LD _{84 were} calculated. The calculations were performed using an authorized computer program. The results of the study are presented in table 4.

Table 4. The effect of hawthorn fruit extract on acute toxicity (lethal effect) of ethyl alcohol. Registration time Indicator (g / kg) The control Hawthorn 200 mg / kg 1 day Ld ₁₆ 6.7 6.8 LD ₅₀ 7.5 ± 0.2 7.7 ± 0.2 LD ₈₄ 8.9 8.8 2 days Ld ₁₆ 7.3 7.5 LD ₅₀ 7.6 ± 0.2 7.8 ± 0.2 LD ₈₄ 7.7 7.9 3 days Ld ₁₆ 6.7 7.4 LD ₅₀ 7.5 ± 0.2 7.8 ± 0.1 LD ₈₄ 8.9 8.9

From the table it follows that the use of extract of hawthorn fruit contributes to a slight increase in the LD _{50 of} ethanol. At the level of the trend, it attenuates the acute toxic effects of ethyl alcohol in mice.

Example 5. The study of the effect of the extract of hawthorn fruit on the ethanol content in rat blood.

Male Wistar rats weighing 220-260 g were injected intragastrically with an extract of hawthorn fruit (freshly prepared aqueous extract with a solids content of 12 mg / ml) at doses of 100 and 200 mg / kg (in terms of dry matter). The rats in the control group were injected with an equal amount of water. The volume of injected fluid did not exceed 15 ml / kg. After 30 minutes, rats of the control and experimental groups were injected intragastrically with ethanol in the form of 30%, w / v, solution at a dose of 4 g / kg. Blood was collected from the tail vessels of rats 3 and 6 hours after ethanol administration. Ethanol was determined by gas chromatography on a chromatograph LHM-80 [Uspensky A.E. et al. Determination of ethanol and acetaldehyde in biological fluids. - Court. expertise. - 1982. - T. 25, No. 3. - S. 45-48]. The results of the study are presented in table 5.

Table 5. The effect of hawthorn fruit extract on the ethanol content (g / l) in rat blood (M ± S.D.) Time Groups of animals (n is the number of rats in the group) after administration The control Hawthorn, Hawthorn, ethanol watch (n 9) 100 mg / kg 200 mg / kg (n 9) (n 9) 3 2.0 ± 0.2 1.9 ± 0.2 1.7 ± 0.3 ** 6 1.4 ± 0.2 1.5 ± 0.1 1.0 ± 0.3 * Note: ** - p <0.05; * p <0.1 in comparison with the control

From the table it follows that the use of extract of hawthorn fruit in a dose of 100 mg / kg does not affect the alcohol content in the blood of animals. At a dose of 200 mg / kg, it reduces blood alcohol level by 15% 3 hours after the introduction of ethanol; after 6 hours, a decrease in this indicator at the trend level is also observed.

Summarizing the above results of experiments on laboratory animals, we can conclude that the extract of hawthorn fruit slightly reduces the toxicity of ethyl alcohol, dose-dependently reduces the time spent by animals in alcohol anesthesia and increases the latency of its onset, dose-dependently accelerates the exit of animals from alcohol intoxication and significantly reduces the content of exogenous ethanol in blood.

Example 6. The study of the effect of the extract of hawthorn fruit on the severity of alcohol intoxication in healthy subjects - volunteers.

The study was conducted on men. During the preliminary selection, people with alcoholism, low alcohol tolerance, and people with abnormal reactions to alcohol or suffering from chronic diseases of the liver, cardiovascular system, and gastrointestinal tract were excluded from the study. 10 people were selected who gave voluntary consent to participate in the experiment. The average age of the subjects was 22.2 years (18-25), the average body weight was 76.6 kg (66-101), and the average height was 175.0 cm (165-187).

The study was carried out in two stages with an interval of 6 days (on Saturdays and Sundays). All subjects were divided into two groups of 5 people each. At the first stage, the subjects of the 1st gr. received extract of hawthorn fruit (freshly prepared water infusion with a solids content of 12 mg / ml) in an amount of 250 ml (about 3.0 g of solids), and the subjects were 2 gr. - equal amount of water (control). In the second stage, on the contrary, the subjects of the 1st gr. received water, and the 2nd gr. - hawthorn fruit extract.

At each stage, a feast with the use of alcohol (vodka) in a dose of 1.0 g / kg was simulated for the subjects. The amount of vodka consumed varied from 220 to 340 ml, depending on body weight. An individual dose of alcohol was consumed fractionally for one hour under a standardized snack (a salad of fresh vegetables and several sandwiches with sausage and cheese) and washed down with either hawthorn fruit extract or water.

2 hours after the end of drinking, the subjects were tested in order to identify the severity of intoxication, which was evaluated through psychological tests, many times described in various manuals and training aids: the ability to switch attention (“black and white table”), the ability to concentrate ( “Proof test”); coordination of movements (fast drawing by a test subject with a jet pen of a line inside a narrow winding corridor printed on a sheet of paper with subsequent fixation of the number of exits outside the corridor); short-term figurative memory ("memory for images"). Additionally, the ability of the subjects to perform the “finger-nasal” test was assessed during the Romberg test (10 squats with closed eyes, shifted feet, arms extended forward and fingers extended).

The results of the study are presented in tables 6-12.

Table 6. The number of reproduced pairs of letters per unit time when performing the test "black and white table" Water (control) Hawthorn 6.7 ± 4.3 9.0 ± 5.1

Table 7. The number of errors (in%) of the total number of reproduced pairs of letters per unit time when performing the test "black and white table" Water (control) Hawthorn 38 ± 29.8 24.5 ± 25.1

Table 8. The number of letters viewed per unit time when assessing the ability to concentrate ("proof test") Water (control) Hawthorn 319.5 ± 58.3 344.4 ± 46.68 *

Table 9. The number of errors in assessing the ability to concentrate ("proof test") Water (control) Hawthorn 3.4 ± 2.3 3.2 ± 1.4

Table 10. The number of exits beyond the gray corridor when assessing coordination of movements Water (control) Hawthorn 18.8 ± 6.4 10.2 ± 4.4 *

Table 11. The number of images reproduced in the test “image memory” Water (control) Hawthorn 3.4 ± 4.1 3.7 ± 3.9

Table 12. Inaccurate execution of the “finger-nasal” test during the Romberg test (in% of the total number of observations) Water (control) Hawthorn 60.0 30,0

According to clinical observation, the subjects developed a state of intoxication of a low degree of severity (increased sociability, talkativeness, motor hyperactivity, increased mood), which reached its maximum severity 1.5-2.0 hours after cessation of alcohol consumption. External differences in the severity of intoxication against the background of water and hawthorn extract were not observed. However, the subjectively assessed, according to test subjects, picture of intoxication in control and experience had significant differences. Nine out of ten subjects said that intoxication against the background of hawthorn fruit extract was less pronounced and was faster.

From the above table materials it follows that according to the results of two tests (the number of errors when performing a proofreading test and the number of images reproduced in the “memory for images” test) there are no differences between control and experience. At the same time, the use of hawthorn fruit extract statistically significantly contributed to the faster completion of the proofreading test (the number of letters scanned per unit time) and the more efficient implementation of the coordination test. In other tests, there is a tendency towards more successful completion of tasks. This was most clearly manifested in the case of performing the "finger-nasal" test during the Romberg test.

Thus, judging by the results of studies conducted on healthy volunteers, a food product - hawthorn fruit extract has the ability to weaken the severity of intoxication or have a sobering effect.

Example 7. Evaluation of the effect of the extract of the fruit of the hawthorn blood-red, introduced into some soft drinks, on the severity of alcohol intoxication in healthy subjects - volunteers.

As compared non-alcoholic drinks, industrially produced non-alcoholic drinks containing caffeine and other tonic ingredients were selected - the Bahmaro non-alcoholic highly carbonated drink based on black tea extract and the Red Devil energy-free soft drink containing caffeine, taurine and a vitamin complex. It is believed that caffeine can have a mild sobering effect.

Water extraction of the blood-red hawthorn fruit was carried out in laboratory conditions. The extract was dried at a temperature of 60 ° C and dissolved in 330 ml of the above beverages at a concentration of 12 mg / ml (1.2%), or a suspension of the dry extract in 330 ml of the above beverages at a concentration of 500 mg / ml (50%) was prepared.

The study was conducted on three healthy men - volunteers aged 25-36 years. Six times with an interval of one week in a friendly feast, the subjects were asked to drink a fixed amount of vodka (350 ml per person).

As a liquid for drinking vodka, they were offered the Bakhmaro drink (330 ml) in the first session of the study; in the second session, a 1.2% solution of dry extract of the blood-red hawthorn fruit in the Bakhmaro drink (330 ml); in the third session - a 50% suspension of the dry extract of the blood-red hawthorn fruit in the Bakhmaro drink (330 ml); in the fourth session - Red Devil drink (330 ml), in the fifth session - 1.2% solution of dry extract of the blood-red hawthorn fruit in Red Devil drink (330 ml); in the sixth session - 50% suspension of dry extract of the fruit of the hawthorn blood red in the drink Red Devil (330 ml). The consumption of the usual snack and the duration of the feast were not limited.

Before each feast, subjects received instructions instructing them to control and evaluate their well-being, the severity and duration of developing alcohol intoxication. After the end of each feast, the subjects were questioned and their subjective sensations were recorded by the tester. The results of the study are presented in table 13.

Table 13. The severity of alcohol intoxication, developing on the background of the use of soft drinks with and without the extract of hawthorn fruit extract Beverages Test subjects No. 1 Number 2 Number 3 Bahmaro Intoxication Intoxication Drunkenness more ordinary. ordinary. expressed by compared to usually developing after use similar dose vodka. Bahmaro with Intoxication Intoxication Intoxication extract weak, fast weak weak hawthorn started to decline. joyful. prompting to (12%) conversation. Bahmaro with Weaker intoxication Intoxication Intoxication extract ordinary weak towards the end weak condition hawthorn characteristic of feasts comfortable (fifty%) this dose of vodka. saved sensation pep Red devil Intoxication a little Intoxication Intoxication lighter than usual. ordinary ordinary Red Devil with Intoxication Intoxication Intoxication extract weak, nice weak weak, nice hawthorn relaxing. well-being relaxing. 1.2% great. Red Devil with Weaker intoxication Intoxication Intoxication extract characteristic of weak condition weak hawthorn this dose of vodka comfortable. is developing fifty% saved slower sensation accompanied by vivacity. enjoyable relaxed

From the table it follows that the tested soft drinks do not affect the severity of intoxication. On the contrary, the same drinks with hawthorn extract in a certain concentration weaken the severity of intoxication. According to the subjects when drinking vodka and tested drinks without extract and with hawthorn extract, there were no unpleasant sensations or other negative effects.

In addition, as shown by experiments on volunteers taking daily alcoholic beverages, when drinking soft drinks with hawthorn extract at a concentration of 1-15% for prophylactic purposes, a weakening of intoxication was observed, which is typical for the usual dose of vodka taken. In addition, a state of vigor remained.

Claims (5)

1. Means for preventing the consequences and reducing the adverse manifestations of acute alcohol intoxication, characterized in that it contains an extract of hawthorn fruit, including procyanidins (from monomers to hexamers with an average degree of polymerization from 1.1 to 5.5) from 1.0-50 , 0 mg / g dry weight of the extract in terms of cyanidin chloride, epicatechins, chlorogenic acid and flavonoids represented by hyperoside, rutin, quercetin, vitexin glycosides, vitexin, isovitexin, orient, isoorientin, apigenin, in general its concentration of phenolic compounds is not less than 10 mg / g of dry weight of the extract in terms of gallic acid. 2. The tool according to claim 1, which contains extracts of the fruits of pharmacopeia species of hawthorn. 3. The tool according to claim 1, which can be made in the form of a solution, suspension, soluble powder, as well as soluble (including effervescent) tablets. 4. The tool according to claim 1 or 3, which additionally contains auxiliary substances, carriers and / or excipients. 5. A soft drink to prevent the consequences and reduce the adverse manifestations of acute alcohol intoxication, characterized in that it contains as an active substance a dry extract of hawthorn fruit according to claim 1 in a concentration of from 1.0 to 60.0%.