RU2245161C1 - Contact-type purgative preparation, pharmaceutical composition upon its basis and method for preventing and treating constipations and affected biorhythm of defecation - Google Patents

Abstract

FIELD: chemical and pharmaceutical industry.

SUBSTANCE: the present innovation deals with creating medicinal preparations of plant origin and could be applied for treating functional constipations and affected biorhythm of defecation. It is suggested to apply either dry aqueous or aqueous-alcoholic extract of horse chestnut seeds of Aesculus species to prepare curative-prophylactic preparation in case of constipation and affected biorhythm of defecation. The suggested preparation should be applied in the form of powder, tablets or suppositories. Pharmaceutical composition for preventing and treating constipation and affected biorhythm of defecation contains an active substance out of medicinal plant and a pharmaceutically acceptable filling agent, moreover, this preparation is designed as suppositories and contains either dry aqueous or aqueous-alcoholic extract of horse chestnut seeds of Aesculus species and suppository hydrophobic foundation at certain content of ingredients. Dry aqueous or aqueous-alcoholic extract contains 1-50% active substance as escin. As foundation it could contain either cacao oil or vitepsol. The method for preventing and treating constipations and affected biorhythm of defecation deals with introducing the suggested pharmaceutical composition into patient's anus 5-15 min before planned act of defecation. Application of "Rectum-activ" preparation provides positive result at treating functional psychogenic constipation: in 5-15 min after introducing a suppository into anus pronounced urgency for defecation. In case of course therapy for 4 wk one should observe restoration of natural urgency for intestinal evacuation. Moreover, purgative preparation causes no unfavorable pain feelings.

EFFECT: higher efficiency.

10 cl, 6 ex

Description

The invention relates to the pharmaceutical industry, in particular to the creation of herbal medicines, and can be used to treat functional constipation and bowel movements.

Constipation is the difficulty (violation) of bowel movement, accompanied by the absence of an independent stool for more than 2-3 days, which requires the use of laxatives or other auxiliary agents. Today this phenomenon is very common both in Western Europe, North America, and Russia. If previously constipation was characteristic of the urban population, today it is often found in rural residents. The prevalence of constipation translates this problem into the category of social, requiring massive diagnostic, therapeutic and preventive measures. The importance of the problem is determined by the fact that many pathological conditions of the colon increase the risk of developing malignant neoplasms or the pathology of functionally related (dependent) organs of the digestive system (gall bladder and bile ducts, stomach, duodenum, pancreas).

Currently, the treatment of constipation is represented by various treatment methods, which include the widespread use of laxatives and diets.

In recent years, overseas oral preparations containing extracts from medicinal plants have increasingly been used abroad for this purpose. So, Senade, Glaxena, Kafiol, Regulaks, Castor oil, Agiolax, etc. are widely used. Almost all laxative herbal remedies are based on senna leaves, buckthorn bark, laxative joster fruits and rhubarb rhizomes containing anthraquinone glycosides (RLS, 2002).

The disadvantage of oral laxatives is a long irritating effect on the entire intestine, a large period of time from the moment of administration to the desired effect, as well as side effects: cramping abdominal pain, frequent loose stools, repeated urge to defecate.

In addition to oral agents, rectal suppositories are used as laxatives. Currently, 9 types of suppositories with a laxative effect are presented on the Russian pharmaceutical market, including 3 domestic ones (Bisacodyl-Nizhpharm, Glycelaks, Glycerol), 6 foreign ones (Bisacodyl, Dulcolax, Laksbene, Flit, Km-glycerophyte, Km-sennofit ) (Radar, 2002). The active ingredients of all these suppositories are 2 substances - bisacodyl and glycerin. Both substances have significant disadvantages. Bisacodyl has a mild laxative effect, and glycerin causes inflammation of the rectum.

The objective of the invention is to develop a new therapeutic and prophylactic agent based on a plant extract with high therapeutic activity aimed at treating constipation of various etiologies: functional (habitual), psychogenic, senile, constipation in inactive patients, as well as constipation associated with a decrease in the sensitivity of the receptor apparatus rectum.

The task is achieved by a group of inventions, united by a single inventive concept.

The use of a dry aqueous or aqueous-alcoholic extract of horse chestnut seeds of the genus Aesculus for the preparation of a therapeutic and prophylactic agent for constipation and defective biorhythm is proposed.

The tool is used in the treatment of constipation of functional, psychogenic, senile, constipation in inactive patients, constipation associated with a decrease in the sensitivity of the receptor apparatus of the rectum.

The tool is used in the form of a powder, in the form of tablets or suppositories.

A pharmaceutical composition is proposed for the prevention and treatment of constipation and disorders of the bowel movement, containing an active substance from a medicinal plant and a pharmaceutical acceptable excipient, the agent being made in the form of a suppository and containing a dry aqueous or aqueous-alcoholic extract of horse chestnut seeds of the genus Aesculus and a suppository hydrophobic base for the following ingredients per 1 candle weighing 1 g:

dry aqueous or hydroalcoholic extract

horse chestnut seed 10-100 mg

suppository hydrophobic base rest.

Dry water or water-alcohol extract of horse chestnut seeds contains 1-50% of the active substance escin.

As a basis, it may contain cocoa butter or witepsol.

A method is also proposed for the prevention and treatment of constipation and biorhythm disorders of defecation, namely, that the pharmaceutical composition is injected into the anus 5-15 minutes before the planned act of defecation.

To restore the natural biorhythm of defecation, the course of treatment is carried out up to 1 month.

The proposed tool is called “Rectum Asset."

Horse chestnut is a large deciduous tree, the leaves are opposite, the flowers are white, collected in erect pyramidal brushes, the fruits are spherical, spiky boxes, seeds are large 3-4 cm in diameter, shiny, brown. Less commonly used are leaves harvested in the first half of summer. For medical purposes, use mature seeds and flowers.

The bark of the trunk and branches contains glycosides: esculin, which upon hydrolysis breaks down into esculletin (6-7-dioxicoumarin), fraxin and glucose; triterpene saponin escin, which gives eszigenin during cleavage; tannins and fatty oil.

Quercetrin, isocvercitrin and quercetin, related to flavono compounds, were found in the leaves of the plant; isolated rutin and spireoside, astragaline; carotenoids lutein, violaxanthin.

The flowers contain quercetrin, rutin, isocvercitrin (Turova, Sapozhnikova, 1982).

Seeds contain coumarin glycosides (esculin, fraxin), flavonoids (quercetin, kempferol), triterpene saponins (escin), fatty oil (5-7%), protein substances (up to 10%), starch (up to 50%), tannins ( 1%), vitamin E, B vitamins (Likarsky roslini, 1989).

Preparations containing horse chestnut seed extracts are used in official medicine as antihemorrhoidal agents and varicose veins in pregnant women and women in childbirth. In patients with varicose syndrome, edema and inflammation after taking the drug are reduced. Positive results in patients with cerebral edema when prescribing chestnut preparations are due to its decongestant effect and are confirmed by the normalization of electroencephalographic parameters (Sokolov, Zamotaev, 1989; Sokolov, 2000).

Preparations from the peel of ripe seeds of horse chestnut are used for prostate adenoma (Gelencir N., 1982) and chronic prostatitis in combination with prostate adenoma (Mamchur F.I., Kushniruk Yu.N., 1992). The aqueous extract from the peel of the fruit slows down the adenomatous transformation and reparatively affects the parts of the prostate gland covered by the process. The mechanism of action of this drug has not been studied, but Polish scientists believe that glycoside esculin in combination with vitamin E, which are rich in chestnut seeds, helps reduce the size and even resorption of small adenomatous nodes (Krylov A.A. et al., 1991; Mamchur F.I. ., Kushniruk Yu.N., 1992).

A fresh homeopathic preparation Aesculus hippocastanum is prepared from freshly purified seeds. The drug is used in breeding from DJ to D2 and is given 2-3 times a day in a few drops: with dry catarrh of the nasopharynx, with hemorrhoidal and trophic ulcers of the leg.

It is believed that horse chestnut bark improves digestion and suppresses the intestinal secretion associated with the inflammatory process. Therefore, it is recommended to use a decoction of chestnut bark for diarrhea. In febrile states, it is advised to use it instead of the bark of a cinchona tree and willow. Also, a decoction of chestnut bark is used to dress festering wounds. Fruits are recommended for coughing with thick sputum. Outwardly, an extract from chestnut fruits is recommended for neuralgia, myalgia, rheumatism, skin inflammation, etc. (Modern phytotherapy, 1988).

Tincture of flowers, bark or leaves, from time to time used in folk medicine, is prepared on the basis of wheat vodka. It is used against vein diseases and for rheumatic complaints. They try to take it with stomach and intestinal pains. In some cases, the chestnuts are roasted, then crushed, mixed with flour and vinegar, and this gruel-like mixture is placed on the hardened breast of nursing mothers to soften it. However, there is no serious need for this, because pharmacies have many ready-made horse chestnut preparations that can be used mainly for venous diseases (Palov, 1998).

Galenic preparations from horse chestnut (Aesculus hippocastanum L): infusions and decoctions from bark, leaves, fruits - have long been used in folk medicine as astringents, choleretic, hemostatic (for uterine and hemorrhoidal bleeding) agents. Different parts of the plant contain in varying amounts saponins, flavonoids (rutin, quercetin) and other organic compounds. Escin is an especially important pharmacologically active substance. Escin (Escin, Aescin, Ascin) - triterpene glycoside with a complex chemical structure; during hydrolysis, it is split into escigenin and three sugar residues. Escin has a pronounced capillaroprotective activity and has an antiexudative (anti-inflammatory) effect. The pharmacological activity of a number of total drugs derived from horse chestnut (eskusan, esflazid, etc.) is largely associated with the presence of escin in them.

Currently, the following chestnut preparations are registered in Russia.

ANAVENOL (Anavenol) *

The combined preparation in the form of dragees containing esculin (close in action to escin) 0.0015 g (1.5 mg), dihydroergocristine (mesylate) 0.0005 g (0.5 mg) and rutin 0.03 g (30 mg) , or in the form of drops containing 1 ml (20 drops) of esculin 0.0015 g (1.5 mg), dihydroergocristine (mesylate) 0.0005 g (0.5 mg) and sodium rutin sulfonate 0.04 g (40 mg).

It is a venotropic drug used in chronic venous diseases: phlebitis, varicose veins, leg ulcers, post-traumatic vein lesions, etc.

The action of the drug is associated with the capillary-protective properties of esculin and rutin and a special effect on the peripheral vessels of dihydroergocristine (see), which, being an α-blocker, causes the expansion of arterioles and, in addition, tones the smooth muscles of the veins. The consequence of this is an improvement in blood circulation in the peripheral vessels.

VENOPLANT (Venoplant) *

Standardized dry horse chestnut seed extract. Contains triterpene glycosides of the escin group.

It has a venotonic and anti-inflammatory (antiexudative) effect. It reduces the increased activity of lysosomal enzymes observed in chronic venous diseases in the capillary wall, as a result of which the vascular permeability decreases, the filtration of low molecular weight proteins, electrolytes and water into the intercellular space is prevented.

Used for impaired venous circulation (varicose veins), chronic venous insufficiency with pain and a feeling of heaviness in the legs, swelling of the legs.

REPARIL (Reparil) *

A capillary-protective and anti-inflammatory drug, the active ingredient of which is triterpene glycoside (saponin) escin, which is found in horse chestnut fruits (seeds).

Reparil is available in the form of dragees, coated with a membrane resistant to the action of gastric juice (reparil-40), and in the form of a gel (reparil-gel).

In the preparation, the capillary-protective and anti-inflammatory properties of escin are mainly used to accelerate the restoration of the function (reparatio) of organs and tissues (reducing swelling, pain) after injuries (including sports), operations, phlebitis, varicose veins, hemorrhoids and some other pathological conditions.

Reparil-gel N. Combination preparation for skin application. Contained in 100 g of gel, 1 g of escin and 5 g of diethylamine salicylate.

It has anti-inflammatory and analgesic effects.

When applied topically, it is absorbed through the skin and is relatively quickly detected in subcutaneous fat and muscle tissue.

It is used for injuries with bruises, sprains, with hematomas, tendovaginitis, lumbosacral radiculitis, lumbago and other pain syndromes, as well as for superficial phlebitis, varicose veins.

ESCUZAN (AESCUSAN®) Queisser Pharma GmbH & Co. (Germany)

Composition and form of release. 100 g of oral solution contain a dry extract from horse chestnut seeds in terms of escin 6.25 g and thiamine hydrochloride chloride i g; in dropper bottles of 20 ml, in 1 pack 1 bottle.

Pharmachologic effect. Venotonic, antiexudative. It reduces the concentration of lysosomal enzymes and inhibits the degradation of mucopolysaccharides in the walls of capillaries. Reduces vascular permeability, preventing the filtration of low molecular weight proteins, electrolytes and water into the lung space.

ESCUZAN 20 (AESCUSAN® 20) Sobering AG (Germany)

Composition and form of release. 1 coated tablet contains a dry horse chestnut extract corresponding to an escin content of 20 mg; in a blister 20 pcs., in a box 2 blisters.

Pharmachologic effect. Venotonic. Reduces the activity of lysosomal enzymes, inhibits the breakdown of mucopolysaccharides in the parietal space of capillaries. Reduces vascular permeability, filtration of low molecular weight proteins, electrolytes and water into the intercellular space.

ESCIN (ESCIN) / DCF /

Triterpene glycoside (saponin) from the fruits (seeds) of horse chestnut (and in the form of sodium salt).

Pharmacological action - decongestant, anti-inflammatory, venotonic, angioprotective. It prevents the activation of lysosomal enzymes that break down proteoglycan, increases the tone of the venous wall, eliminates venous congestion; reduces capillary permeability and fragility. Increased venous blood flow has a beneficial effect in diseases accompanied by venous congestion (especially in the lower extremities), edema, trophic damage to the walls of blood vessels, inflammatory processes and venous thrombosis, contributes to the repair of organs and tissues.

ESSAVEN-GEL (Essaven) *

A gel containing 100 g: escin 1 g, heparin sodium salt 10,000 ME, phospholipids, unsaturated fatty acids (linoleic, linolenic, oleic), ethyl alcohol.

Used for disorders of venous circulation: varicose veins, inflammation of superficial veins, edema, bruises, sprains, sports injuries.

Esflazid (Aesflazidum)

The combined preparation (from horse chestnut) in the form of tablets containing escin (from the fruit) 0.005 g (5 mg) and the sum of flavonoids (from the leaves) - flavazide 0.025 g (25 mg).

The content of active substances and therapeutic effect is close to eskusan.

Used for phlebitis, thrombophlebitis, hemorrhoids. The proposed tool contains a dry aqueous or aqueous-alcoholic extract of seeds of horse chestnut of the genus Aesculus.

Dry water or dry water-alcohol extract of chestnut seeds is prepared according to the requirements of the existing pharmacopoeia.

The pharmaceutical composition in the form of suppositories is distinguished by the content of horse chestnut seed extract in 1 suppository (for children — 15 mg, 25 mg; adults — 50 mg, 100 mg).

The tool is prepared as follows.

Example 1. To 985 grams of molten fat base (cocoa butter, vitepsol, etc.), heated to a temperature of 40-45 ° C, add 15 grams of dry horse chestnut seed extract and mix thoroughly in a mixer until the extract is evenly distributed in the base. The resulting candle mass is poured into a chilled casting mold for 1000 candles weighing 1 gram each.

Example 2. To 975 grams of molten fat base (cocoa butter, vitepsol, etc.), heated to a temperature of 40-45 ° C, add 25 grams of dry horse chestnut seed extract and mix thoroughly in a mixer until the extract is evenly distributed in the base. The resulting candle mass is poured into a chilled casting mold for 1000 candles weighing 1 gram each.

Example 3. To 950 grams of molten fat base (cocoa butter, vitepsol, etc.), heated to a temperature of 40-45 ° C, add 50 grams of dry horse chestnut seed extract and mix thoroughly in a mixer until the extract is evenly distributed in the base. The resulting candle mass is poured into a chilled casting mold for 1000 candles weighing 1 gram each.

Example 4. To 900 grams of molten fat base (cocoa butter, vitepsol, etc.), heated to a temperature of 40-45 ° C, add 100 grams of dry horse chestnut seed extract and mix thoroughly in a mixer until the extract is evenly distributed in the base. The resulting candle mass is poured into a chilled casting mold for 1000 candles weighing 1 gram each.

Suppositories "Rectum Asset" have a light brown color. The active ingredients of the drug are triterpene saponins of the β-amirin group, of which the main escin, a derivative of escigenin. The absence of thermal effects and heat-mass transfer processes leading to the loss of some components of the extract during the preparation of the preparation ensures the preservation of the entire complex of biologically active substances in their native state.

Dosage and administration.

Having previously released the suppository from the contour packaging, enter it into the anus 5-15 minutes before the planned act of defecation. To restore the lost natural biorhythm of defecation, course treatment is carried out for 1 month.

The drug was tested on volunteers suffering from constipation, namely:

Functional constipation - 7 people,

Psychogenic constipation - 5 people,

Senile constipation - 3 people

According to clinical observations, a high effect of this drug can be noted.

The drug showed a very high effect in the treatment of patients with functional and psychogenic constipation.

The invention is illustrated by the following examples.

Example 1. Patient M., 35 years old, the diagnosis of chronic functional constipation. Prior to this, over the past few years, it has been unsuccessfully treated with various laxatives, mainly teas containing senna and cleansing enemas. Rectum-active suppositories were prescribed once a day, in the morning, immediately after waking up. A strong desire for bowel movement arose every time 5-7 minutes after the introduction of the suppository into the rectum. After a month's course of using suppositories, a complete restoration of the natural urge to defecate was noted. The patient stated that after the suppository was canceled, she had a natural urge to defecate every 15-30 minutes every day after waking up, and her irritability and headaches disappeared.

Example 2. Patient K., 25 years old, diagnosed with dyshesia. A disease of a psychogenic nature arose 7 years ago during the course of military service in the army. Upon returning from the army, I tried to treat myself with candles with bisacodyl and glycerin, but did not get a positive result. Suppositories with bisacodyl did not cause a laxative effect, and suppositories with glycerin caused persistent inflammation of the rectum. To remove the inflammatory process in the rectum, he made microclysters with vegetable oil. A course of treatment with suppositories “Rectum-asset” was carried out according to the scheme: 1 suppository per day in the morning immediately after waking up. A strong desire for bowel movement arose every time 5-15 minutes after the introduction of the suppository into the rectum. After 30 days of treatment, after discontinuation of the drug, without a suppository in the morning, natural urge to defecate appeared, acne and abdominal pain disappeared.

These observations show that the use of the “Rectum-active” drug gives a positive result in the treatment of functional and psychogenic constipation, ie 5-15 minutes after the introduction of the suppository into the anus, strongly expressed urges to defecate occur. With a course of treatment for 4 weeks, a restoration of the natural urge to empty the intestine was noted. In addition, a laxative does not cause unpleasant pain.

Claims (10)

1. The use of a dry aqueous or aqueous-alcoholic extract of horse chestnut seeds of the genus Aesculus for the preparation of a therapeutic and prophylactic agent for constipation and bowel movement disorders. 2. The use according to claim 1, characterized in that the tool is used in the treatment of constipation of functional, psychogenic, senile, constipation in inactive patients, constipation associated with a decrease in the sensitivity of the receptor apparatus of the rectum. 3. The use according to claim 1, characterized in that the tool is used in powder form. 4. The use according to claim 1, characterized in that the tool is used in tablet form. 5. The use according to claim 1, characterized in that the tool is used in the form of suppositories. 6. A pharmaceutical composition for the prevention and treatment of constipation and disorders of the bowel movement, containing an active substance from a medicinal plant and a pharmaceutical acceptable excipient, characterized in that it is in the form of a suppository and contains a dry aqueous or hydroalcoholic extract of horse chestnut seeds of the genus Aesculus and suppository hydrophobic base with the following ingredients per 1 candle weighing 1 g: Dry aqueous or hydroalcoholic extract horse chestnut seed 10-100 mg Suppository hydrophobic base 7. The pharmaceutical composition according to claim 6, characterized in that the dry aqueous or hydroalcoholic horse chestnut seed extract contains 1-50% of the active substance escin. 8. The pharmaceutical composition according to claim 6, characterized in that it contains cocoa butter or witepsol as a base. 9. A method for the prevention and treatment of constipation and biorhythm defecation disorders, characterized in that the suppository according to claim 6 is inserted into the anus 5-15 minutes before the planned act of defecation. 10. The method according to claim 9, to restore the natural biorhythm of defecation, the course of treatment is carried out up to 1 month.