RU2600795C1 - Vegetable composition in the form of a micellar solution - Google Patents

Abstract

FIELD: pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, namely to a composition, possessing anti-inflammatory and throat softening effect. Composition possessing anti-inflammatory and throat softening effect, represents a micellar solution and comprises an eucalyptus extract, echinacea extract, sodium alginate or methyl cellulose, as auxiliary substances, mixture of nonionic surfactants TWEEN-20 and TWEEN-80; 96 % ethyl alcohol and water at certain ratio of components.

EFFECT: described composition provides prolonged effect, possesses high therapeutic effect, prevents dry mouth.

1 cl, 1 tbl, 3 ex

Description

The invention relates to medicine, namely to a composition based on plant materials of extracts of echinacea and eucalyptus, intended for the treatment and prevention of diseases of the upper respiratory tract, with antiseptic and prolonged action, preventing the appearance of dry mouth.

Against the background of the unfavorable environmental situation, the number of various diseases, for example, the upper respiratory tract and throat, has significantly increased. In this regard, active research is currently underway in terms of the search for new anti-inflammatory, immunostimulating drugs. However, most of these drugs are individual chemicals, which often roughly interfere with the activity of the immune system and cause a number of side effects, for example, in the form of local irritations. Therefore, it is no coincidence that medicinal plants began to fall into the field of view of scientists more and more as a source of mild immunomodulating agents, plant extracts with antiseptic and anti-inflammatory effects. One of the groups of such plants are species of the genus Echinacea (Echinacea L.).

A wide range of anti-inflammatory drugs are available for the treatment of the respiratory tract and throat. The composition of the preparations may include from two or more active ingredients of both natural and synthetic origin.

The development of non-toxic preparations of plant origin, which have a favorable profile of efficacy and safety, allowing gently and physiologically to provide an antibacterial effect, without exerting toxic effects on internal organs, is a priority. Such drugs can be prescribed for children, pregnant women, as well as patients with age-related liver and kidney failure.

Today, in folk medicine, there are known methods of treating diseases of the upper respiratory tract with plants (Lavrenov V., Lavrenova G. Encyclopedia of practical phytotherapy. Publishing house "Stalker", 2001, 590 pp .; Reference "Phytotherapy with the basics of clinical pharmacology." / Edited by VG Kukes. M.: “Medicine”, 1999, 187 pp.). Plants such as calendula, common basil, medicinal sage, pharmacy chamomile, St. John's wort perforated, thyme ordinary are used. However, the above medicinal plants may also have an irritating effect on the mucous membrane of the gastrointestinal tract when ingested and cannot be widely used in therapeutic practice for children, patients with diseases of the gastrointestinal tract, bronchial asthma, chronic obstructive bronchitis, diseases of the reproductive system. In the case of application of fees, the totality of chemically active compounds in medicinal plants does not always allow one to predict with complete confidence the integral clinical effect.

Dry echinacea extract is widely used to treat diseases of the upper respiratory tract. According to Russian and German scientists, Echinacea grass contains two groups of biologically active compounds - phenylpropanoids, in particular chicoric acid, and polysaccharides, which have antimicrobial, anti-blast, and immunostimulating effects. This circumstance was taken into account by the authors when developing the claimed composition.

Taking into account the available raw material base of Echinacea purpurea in the Russian Federation, as well as the need for practical health care for plant-based immunomodulating, anti-inflammatory drugs that are accessible to the general population, the problem of creating drugs based on the raw materials of this plant is relevant.

Thus, the grass of Echinacea purpurea (Echinacea purpurea (L.) Moench.], Echinacea angustifolia (Echinacea angustifolia Moench.) And other species serves as a source of such foreign drugs as “The Tincture of Echinacea Dr. Tays”, “Echinacin”, “Immunal”, Echinafors, Parodontax, et al. [Bauer R., Wagner N. Echinacea: Handbuch fur Arzte Apotheker und andere Naturwissenschaftler. - Stuttgart: Wissenschaftliche Verlagsgeselschaft, 1990. - 182 s.). The known preparations "Echinacin liquidum" (series 518626, Germany) and "Immunal" (series 0401195, Slovenia) obtained by pressing a freshly picked plant and adding 22 or 20% ethyl alcohol

A known composition based on plant materials for the treatment of acute respiratory diseases (ARI) (US Pat. RF No. 2080868), namely, tinctures of elderberry, mullein, duckweed, echinacea, wormwood, wolf bast, Persian chamomile, sneezing grass, taken 10 g , and 100 g of a 1% solution of burnt alum with a physiologically acceptable carrier. This tool can be made in the form of drops, capsules, tablets, lozenges. It is known that Echinacea pills can cause itching, swelling of the face, skin rash, difficulty breathing.

A number of pharmacological preparations based on substances of various species of plants of the genus Echinacea are known, as well as various methods for their preparation from various parts of plants: roots, inflorescences and terrestrial parts (US Pat. RF No. 2163138). So, this patent describes a water-alcohol tincture based on extractive substances Echinacea.

Known means for the treatment and prevention of tonsillitis, stomatitis, gingivitis, pharyngitis, laryngitis, etc. (Pat. RF №2125456), containing apis, belladonna, phytolucus, calendula, mercury solubilis, echinacea and ethyl alcohol 70% in a certain ratio. The disadvantage is that the drug is an alcohol tincture; the use of the collection does not allow predicting the clinical effect.

Known application in folk medicine tinctures of eucalyptus for diseases of the respiratory tract for rinsing or inhalation. It is not recommended to use eucalyptus inside children under 2 years of age. Contraindications exist for inhalations - for patients with whooping cough, bronchial asthma and respiratory tract spasms, with severe damage to the kidneys and liver.

In European Pharmacopoeia, phytotherapy mainly uses eucalyptus extract obtained from leaves, flowers, fruits, stems or bark of eucalyptus, preferably from eucalyptus leaves. Eucalyptus leaves are traditionally used orally and topically for the treatment of diseases of the respiratory system (bronchitis, sore throat, nasal congestion, runny nose, etc.) or overlay for the treatment of wounds, skin ulcers, etc. The specified eucalyptus extract is obtained by the extraction method, carried out by the usual stages known to the specialist. The leaves, flowers, fruits, stems or stem of the eucalyptus (Eucalyptus sp.) Or a mixture of these parts is ground, then extracted with an organic solvent or a mixture of water and an organic solvent or solvents miscible with water (for example, a water-alcohol mixture).

Most often, eucalyptus is used as a flavoring in various herbal medicines (US Pat. RF No. 2384201, 2396941, 2487710) or in compositions to provide a sensation similar to that caused by menthol (US Pat. RF No. 2398476).

As a prototype, we selected a composition for the treatment of diseases of the upper respiratory tract, etc. (US Pat. RF No. 2125456), containing echinacea and other medicinal plants, ethyl alcohol 70% in a certain ratio. The disadvantage is that the drug is an alcohol tincture, it is not approved for use by children and pregnant women.

The main objective of the invention is the creation of a new anti-inflammatory and softening throat composition based on eucalyptus extract and echinacea, which effectively suppresses inflammation in the throat, prevents the occurrence of dry mouth and is characterized by a prolonged action. In addition, the purpose of this invention is to increase the shelf life of the composition.

Based on the experience of using extracts of eucalyptus and echinacea, the authors proposed a new anti-inflammatory composition, as well as a convenient form of application in the form of a micellar solution, which can be used in the form of a spray.

The goal is achieved by using a composition of plant origin in the form of a micellar solution, consisting of a mixture of extracts of echinacea and eucalyptus, excipients, including an aqueous-alcoholic solution. Additionally, the composition contains as auxiliary substances sodium alginate or methyl cellulose, a mixture of non-ionic surfactants TWIN-20 and TWIN-80, taken in a ratio of 1: 4, in the following ratio, wt.%:

eucalyptus extract 0.1-0.5 echinacea extract 0.1-0.5 sodium alginate or methyl cellulose 1.5-3.0 a mixture of nonionic surfactants 0.1-1.0 ethanol 1.0-1.5 water the rest is up to 100%

In addition, the composition may additionally contain a preservative nipagin in an amount of 0.05-0.2 wt.% Or nipazole in an amount of 0.02-0.03 wt.%.

The following substances were used as auxiliary compounds.

Oxyethylated sorbitans were used as a mixture of nonionic surfactants. Polysorbate-20 is a derivative of lauryl acid, TWIN-20. Polysorbate-80 is a monooleate with a degree of hydroxyethylation of 20, TWIN-80. Sodium alginate is a salt of alginic acid, a natural polysaccharide extracted from red and brown seaweeds. It is used as a thickener, stabilizer. Methyl cellulose - is used in the pharmaceutical industry as a stabilizer, film former and emulsifier.

Nipagin and nipazole, if necessary, are added to aqueous solutions as preservatives, are approved for medical use, are used in the pharmaceutical industry, in cosmetics, and in food products to extend shelf life.

Nipagin is a methyl ester of para-hydroxybenzoic acid. It is used as a preservative and antiseptic. The substance actively inhibits the growth of gram-positive bacteria, less active against gram-negative bacteria and molds. It is mainly used in combination with other preservatives.

Nipazole is a p-hydroxybenzoic acid propyl ester. Its bactericidal effect is more than 5 times higher than nipagin. It is quite effective against fungi and gram-positive bacteria.

As a result of an intensive study conducted by the inventors to achieve the aforementioned goals, new compositions have been developed for oral administration by using an extract from medicinal herbs of natural origin. To increase the therapeutic effect of water-insoluble extracts of echinacea and eucalyptus, a physicochemical method was used to transfer these components to lyophilic nanodispersion in an aqueous medium. The technique used in this work consists in solubilizing extracts in mixed surfactant micelles (TWIN-20, TWIN-80).

Distinctive features of the resulting composition for production are:

firstly, the use of a mixture of nonionic surfactants TWIN-20 and TWIN-80 in a ratio of 1: 4, which provides a content of surfactant molecules with a saturated hydrocarbon radical of 30-35% (wt.) and an unsaturated hydrocarbon radical of 70-65% (wt.) . This ratio of hydrophobic (hydrocarbon) parts of surfactant molecules determines the optimal conditions for the inclusion (solubilization) of active substances in the volume of micelles;

secondly, obtaining a micellar solution of extracts of active substances, carried out by adding an alcoholic solution of extracts of active substances and a mixture of surfactants in an aqueous solution of methylcellulose or sodium alginate. This method of obtaining a nanodispersed system allows to obtain a narrow distribution of micelles in size with a high degree of solubilization of the LHC in them. Micelles (spherical and cylindrical) obtained under the used conditions have an average size of 10 to 50 nm, which ensures high therapeutic activity of the composition and colloidal stability of the drug during storage;

thirdly, the inclusion of methyl cellulose and sodium alginate in the composition of the drug composition provides the formation of a thin film on the treated throat surface. Aqueous solutions of methylcellulose and sodium alginate in the presence of a surfactant (a mixture of Tween-20 and Tween-80) moisten the mucin layer, which forms the mucous surface of the throat, well. The resulting thin film, having a thickness of the order of 50 μm, has an increased viscosity due to the orientation of the polymer molecules and the participation of surfactant micelles in the formation of the supramolecular structure in the thin layer. Structuring of a disperse system in a thin film determines an increase in its viscosity, which significantly slows down the process of rinsing (draining) a drug from a treated surface. The latter determines the prolonged action of the developed composition, about 4-6 hours, depending on the physiological characteristics of the patient.

The proposed composition in the form of a micellar form of an aqueous dispersion of hydrophobic biologically active extracts of eucalyptus and echinacea with the optimal, from the point of view of solubilization capacity of micelles, ratio of saturated and unsaturated hydrocarbon parts of surfactant molecules (Tween-20 and Tween-80 mixtures), a method for producing a micellar solution by mixing alcohol solution of biologically active extracts and surfactants with an aqueous solution of sodium alginate or methyl cellulose, as well as the use of a polymer-micellar solution to obtain a tone oh highly viscous film on the treated surface of the throat provide prolonged action of the composition, a high therapeutic effect and prevent dry mouth.

Example 1. Preparation of composition

102.0 g of a 96% aqueous solution of ethyl alcohol, 10.0 g of echinacea extract, 10.0 g of eucalyptus extract, 2.0 g of Tween-20, 8.0 g of Tween-80 are placed in a round-bottom flask. The flask is heated in a water bath to a temperature of 40-45 ° C under a reflux condenser (cooling water temperature of 12-17 ° C). The duration of heating is 30-40 minutes. Under these conditions, the components are completely dissolved. In parallel, a solution of 150.0 g of methyl cellulose in 9718.0 g of prepared water is prepared in a 12-liter reactor equipped with a stirrer. The system is stirred for 15-20 minutes at a speed of 150-200 rpm.

After dissolving methyl cellulose with stirring at a speed of 150-200 rpm add an alcohol solution (flow rate of 50 ml / minute). Stirring is continued for 20-25 minutes after adding the entire volume of the alcohol solution.

The resulting composition is packaged in bottles with a spray device.

Example 2. Similarly, the composition was obtained with sodium alginate

In a round-bottom flask, 102.0 g of a 96% aqueous solution of ethyl alcohol, 10 g of echinacea extract, 10 g of eucalyptus extract, 2.0 g of Tween-20, 8.0 g of Tween-80 are placed. The flask is heated in a water bath to a temperature of 40-45 ° C under a reflux condenser (cooling water temperature of 12-17 ° C). The duration of heating is 30-40 minutes. Under these conditions, the components are completely dissolved. In parallel, in a 12-liter reactor equipped with a stirrer, a solution of 150 g of sodium alginate in 9718.0 g of prepared water is prepared. The system is stirred for 15-20 minutes at a speed of 150-200 rpm. After dissolving the sodium alginate with stirring at a speed of 150-200 rpm add an alcohol solution (flow rate of 50 ml / minute). Stirring is continued for 20-25 minutes after adding the entire volume of the alcohol solution.

Before packing into vials, nipagin or nipazole in the required amount can be added to the resulting composition.

The resulting composition is packaged in bottles with a spray device.

Example 3. Preparation of the proposed composition

The following compositions of the composition were prepared, indicated in table. 1. Similar results were obtained using the preservatives of nipagin in an amount of 0.05 wt.% And nipazole in an amount of 0.02 wt.%.

Particle sizes in the micellar solution of the therapeutic composition can range from 10 to 70 nm. Alternatively, such compositions can be easily applied as a spray.

The auxiliary substances used (surfactants, polymers) act as stabilizers and film formers, preventing the coagulation of nanoparticles during the formation of the colloidal system at all stages of production, storage and use, and also provide a prolonged action due to the increased viscosity of the formed film on the treated surface.

The resulting composition has bioavailability and, therefore, a lower degree of side effects compared with free active substances and is able to withstand long-term storage of up to 3.5 years.

Claims (2)

1. The composition has anti-inflammatory and softening the throat effect, characterized in that it is a micellar solution and contains eucalyptus extract, echinacea extract, sodium alginate or methyl cellulose, a mixture of non-ionic surfactants TWIN-20 and TWIN-80 taken in the ratio 1: 4, 96% ethyl alcohol and water in the following ratio of components, wt.%:
eucalyptus extract 0.1-0.5 echinacea extract 0.1-0.5 sodium alginate or methyl cellulose 1.5-3.0 a mixture of nonionic surfactants 0.1-1.0 96% ethyl alcohol 1.0-1.5 water the rest is up to 100% 2. The composition according to p. 1, characterized in that it further comprises a preservative nipagin in an amount of 0.05-0.2 wt.% Or nipazole in an amount of 0.02-0.03 wt.%.