RU2372096C1 - Fungicidal, antiinfective and viricidal phytoextract composition (versions) - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention concerns chemical-pharmaceutical industry, and can find application in manufacturing of medical, preventive, cosmetic and sanitary-and-hygienic agents like gels, sprays, balms, creams, lotions and liquids for wipes of disinfecting and sanitation actions with antifungal, antiinfective and antiviral activity without by-effects. An effective fungicidal, antiinfective, viricidal, adaptogenic and antiradiation agent contains the active substances made of vegetable raw bee balm in the form of oily, water-alcohol extracts and bee balm essence.

EFFECT: bee balm extract complex (BBEC) as a stabilised suspension of phospholipid vesicles allow incorporating lipophilic and hydrophilic fractions of complex active substances of bee balm as one structure, provides their stable transport and possesses expressed inactivating activity in relation to pathogenic microorganisms (viruses, bacteria, fungi and protozoa).

4 cl, 4 ex, 1 tbl, 1 dwg.

Description

The invention relates to the pharmaceutical industry and may find application in the manufacture of therapeutic, prophylactic, cosmetic and sanitary-hygienic products such as gels, sprays, balms, creams, lotions and liquids with a disinfecting and healing effect with fungicidal, antimicrobial and virucidal effects.

Environmental degradation, the spread of antibiotic-resistant strains of microorganisms has an increasingly strong effect on human health. In this regard, the search for effective environmentally friendly innovative forms of drugs is necessary.

Fractions from plant materials, including essential oils, are natural factors with a wide range of positive effects on many body systems. They have a universal preventive effect, have a pronounced therapeutic effect and have several advantages over other means, because their properties are provided by multicomponent compounds, many of which are similar in chemical structure and biological effect to endogenous compounds involved in the bioregulation of physiological systems of the macroorganism. Since the development of various forms of pathology, due to environmental factors, is characterized by the complexity and versatility of the violation of regulation systems, this becomes especially important and relevant. In this case, it is important to take into account the concentration of the active components, their set and combinations. The maximum positive effects are observed when using the most complete extraction of active molecules from plant materials and when using low concentrations due to the fact that the responses require less energy. The mild action of herbal preparations, good tolerance, the absence of toxic effects with prolonged use, the absence of contraindications for use and a pronounced bioregulatory effect - all this is their advantage over other known drugs and provides the possibility of individual and mass application.

The effectiveness of herbal remedies has been convincingly proven by a number of works in the field of medicine, veterinary medicine and cosmetology. The advantage of herbal preparations over synthetic ones is that when they are used according to indications and in recommended doses, a long-lasting effect is achieved without relapses and seasonal exacerbations of many chronic and systemic diseases.

The use of drugs of this class made it possible to create entire areas in medicine and various sections of healthcare. Taking into account the latest technological advances in the production of preparations with nanoparticles, including the preparation of finely dispersed systems saturated with lipophilic and hydrophilic mixtures, one can count on success in creating and putting into practice the means of a new generation of phytopreparations, in particular, with extracts of monarda monada fistulosa). Varieties of monarda are known under the names of melissa tubular, golden, Turkish, it is used for canning vegetables, as a spice in salads, green soups, for stewing meat and fish, gives a pleasant aroma to herbal teas, and is used in the production of vermouth and cheese. Monarda dry raw materials and extracts from it are widely used. Essential oil (EM) from monarda is isolated by hydrodistillation of the whole plant. When extracted with oil, in addition to the essential oil fraction, flavonoids are secreted; accordingly, alcohol-soluble compounds, including chlorophyll, are obtained by water-alcohol extraction.

It is known that extracts from monarda have a wide spectrum of antimicrobial activity, which is manifested against bacteria, including mycoplasmas, viruses, fungi, L-forms of bacteria. In addition, extracts from monarda have immunomodulating, antioxidant, radioprotective, desensitizing, anti-cancer, adaptogenic effects on the human body (V.V. Nikolayevsky, V.I. Zinkovich. Plant aromas and human health. Tolyatti, 1997, p. 110-114 )

Known compositions containing water-alcohol extracts from the herb monarda to create medicines (RF patent No. 2155071 A61K 47/34 9/00, 2000, Bull. No. 24).

It is known that monarda extracts are included in the production of food and alcoholic beverages (RF patents No. 2239653, C12G 3/06, 2004; No. 2228040, А23В 4/20, 2004).

Known methods of cultivating monarda in Siberia, and also developed a method for producing an oil extract from Monarda fistulosa. Convincing evidence is presented of the high antimicrobial and fungicidal activity of this drug and its other positive properties (RF patents No. 2250596, IPC A01G 1/00, 2005, Bull. No. 12; No. 2244552, IPC A61K 36/78, 2005).

Known application tool and method for its production, containing water-alcohol extracts from the herb monad duodea and poplar buds (RF patent No. 2179456 A61L 26/00, 15/58, 2002, Bull. No. 5). The tool also contains extracts from another 14 types of medicinal plants and is intended to expand the range of drugs of prolonged action in the form of film formers from natural raw materials.

The disadvantages of the known funds are the use of DMSO as a penetrator, provoking local skin irritation, violation of the protective lipid barrier, as well as a high alcohol content (from 7.8 to 39%).

The closest in technical essence to the present invention is a therapeutic and prophylactic cosmetic product containing, as active agents, microparticles of colloidal silver, essential oils of monarda and tea tree, enclosed in a lipid component and distributed in a gel medium with preservatives, plant extracts, essential oils and stabilizing additives (RF patent No. 2167650, IPC АКК 9/10, 9/06, 2001, Bull. No. 15).

The disadvantage of the prototype is the use of only monarda essential oil and only as an auxiliary component that enhances the action of silver, and in one concentration, which significantly reduces the effectiveness against many microorganisms, usually comprising a population of pathogens. The absence of other active substances from the monarda in the product, in particular flavonoids, limits the scope and does not allow it to be used as fungicidal, antimicrobial, virucidal.

The objective of the invention is the creation of a unified complex means of a new generation with high fungicidal, antimicrobial and virucidal activity based on a complete set of active substances obtained from Monarda fistulosa in combination with extracts of other plants, in liposome form.

As a result of the use of the present invention, it becomes possible to expand the range of environmentally friendly highly effective fungicidal, antimicrobial and antiviral compositions based on natural phytoextract compounds with pronounced inactivating activity against pathogenic microorganisms (viruses, bacteria, fungi, including mold, and protozoa) and This has a general strengthening and adaptogenic effect on the human body, and the most environmentalist in another way. The use of the proposed composition provides the treatment and prevention of microbial etiology and closed space infections by physiological methods - exposure to pathogenic forms of microorganisms (bacteria, viruses and fungi, including molds) while enhancing the protective properties of the human body.

The above result is achieved by the fact that the proposed composition having a fungicidal, antimicrobial and virucidal effect contains, as a base, oil, water-alcohol extracts and aromatic monarda essential oil - Monarda fistulosa, propylene-glycolic extracts of pine and poplar, peppermint essential oil, basil, aristoflex, gum, lecithin, glycerin, epofen, charomix (propylene glycol solution of methyl and propyl esters of paraoxybenzoic acid) and water in the following ratio of components, wt.%:

Monarda Oil Extract 0.5-3.0 Hydroalcoholic extract of monarda 0.1-2.0 Monarda essential oil 0.03-1.0 Pine extract 0.5-1.0 Poplar extract 0.5-1.0 Peppermint essential oil 0.05-0.2 Basil Essential Oil 0.07-0.1 Aristoflex 0.2-1.0 Gum 0.01-0.9 Lecithin 0.1-7.0 Glycerol 1.0-5.0 Epofen 0.001-0.1 Sharomiks 0.001-0.5 Water Rest

In another embodiment, the proposed composition having a fungicidal, antimicrobial and virucidal effect, contains as a base oil, water-alcohol extracts and monarda essential oil - Monarda fistulosa, propylene glycol extracts of calendula, linden, grapefruit, hyssop and rose essential oil, aristoflex, lecithin, glycerin, epofen, charomix and water in the following ratio of components, wt.%:

Monarda Oil Extract 0.5-1.5 Hydroalcoholic extract of monarda 0.1-1.5 Monarda essential oil 0.1-0.3 Calendula Propylene Glycol Extract 0.5-1.0 Propylene Glycolic Linden Extract 0.5-1.0 Grapefruit essential oil 0.05-0.2 Hyssop essential oil 0.01-0.02 Rose essential oil 0.01-0.05 Aristoflex 0.2-1.0 Lecithin 0.1-5.0 Epofen 0.001-0.1 Glycerol 1.0-5.0 Sharomiks 0.5-0.8 Water Rest

In another embodiment, the proposed composition having a fungicidal, antimicrobial and virucidal effect, contains as a base oil, water-alcohol extracts and monarda essential oil - Monarda fistulosa, propylene glycol extracts from pine and cornflower, essential oils of grapefruit and rosemary, aristoflex, gum , glycerin, epofen, charomix and water in the following ratio of components, wt.%:

Monarda Oil Extract 0.05-0.7 Hydroalcoholic extract of monarda 0.05-0.5 Monarda essential oil 0.01-0.1 Propylene glycol pine extract 0.5-1.0 Cornflower propylene glycol extract 0.5-1.0 Grapefruit essential oil 0.05-0.2 Rosemary Essential Oil 0.05-0.1 Aristoflex 0.2-1.0 Gum 0.1-0.5 Glycerol 1.0-5.0 Epofen 0.001-0.1 Sharomiks 0.4-0.6 Water Rest

The use of not only one, but several fractions - extracts of plant material monarda in the composition in combination with extracts of other plants in liposomal form, provides potentiation of their action, expands the range of points of application. The tool has anti-inflammatory, pronounced antimicrobial, fungicidal, virucidal, bronchodilator, etc., including the normalizing function of the immune system, action. Monarda extract fractions and other biologically active substances incorporated into phospholipid vesicles inactivate pathogenic microbes and viruses, which contributes to the rapid elimination of microbial air pollution, its refreshment, and increased humidity.

The formula of the proposed compositions containing stabilized fractions of the monarda, can be used in the form of creams, balms and health-improving gels for humans.

It became possible to use a gel spray to clean the air when the smallest aerosol drops generated by spraying the proposed product, consisting of water, a complex of extracts from monarda and other plants and gelling agents-sorbents, bind and neutralize a suspension of pathogenic microbial particles and dust from the air. Processing can be carried out in the presence of people due to the safety of the product. Due to the pleasant smell of special compositions of essential oils, the product has an aromatherapy effect.

The formation of liposomes is carried out by the method of ultra-rapid dispersion with a powdery substance (RF patent No. 2311499 C2, IPC C11B 1/00, 2007, Bull. No. 33). The stabilization of the monarda extract complex (CEM) in phospholipid vesicles ranging in size from 30 nm to 150 nm is controlled by spectrophotometry and electron microscopy.

The process of preparing the proposed composition with fungicidal, antimicrobial and virucidal action based on a complex of monarda extracts

1. Component preparation

Aristoflex structurant (gellant) is prepared by its swelling in structured water with constant stirring.

Gum (gelling agent and sorbent) is prepared by the method of its swelling in structured water with constant stirring.

Glycerin (skin moisturizer and plasticizer of the finished gel form) is mixed with sharomiks (preservative) and introduced into the mixing tank.

Water-soluble components (epophene - antioxidant, plant extracts) are dissolved immediately before administration.

Oil and water-alcohol extracts, as well as essential oils, including monarda, are mixed with lecithin using a laboratory homogenizer until smooth.

Liposomes are obtained on an ultra-fast homogenizer of any type at a speed of 2 thousand rpm.

The finished suspension of liposomes is introduced into the mixing reactor.

2. The technology of preparation of the proposed composition

Aristoflex and gum builders, solutions of plant extracts of pine, poplar, linden, calendula, cornflower, etc. are subsequently introduced into the mixer tank. Then, a suspension of liposomes with incorporated extracts of monarda and essential oils is introduced, mixed well until a homogeneous mass, pH is checked (from 6, 0 to 7.0) of the finished product at room temperature.

The preparation of compositions is carried out according to a single technology, using various concentrations of active components. The concentration of the introduced liposome composition and extract solutions from medicinal plants depends on the purpose of the drug. For example, to achieve antimicrobial action, monard concentrations from 0.1 to 1.5% are used, to achieve fungicidal action, from 0.3 to 3.0%, for virucidal, from 0.1 to 0.5%.

Specific examples of the invention are presented below. The presented examples are not limited to the list of possibly obtained compositions based on extracts of monarda with fungicidal, antimicrobial and virucidal effects.

Example 1. A composition having a fungicidal, antimicrobial and virucidal effect, for example, in the treatment and prevention of dental diseases, for the safe disinfection, treatment and prevention of fungal diseases of the legs and nail plates, for the treatment and prevention of viral diseases, contains oil, water-alcohol extracts and monarda essential oil, propylene-glycolic extracts of pine and poplar, essential oils of hyssop, basil, aristoflex, gum, lecithin (phosphatisylethanolamine), glycerin, epofen, charomix (propylene glyco left solution of methyl and propyl esters of para-hydroxybenzoic acid) in the following ratio of components, wt.%:

Monarda Oil Extract 2.5 Hydroalcoholic extract of monarda 0.7 Monarda essential oil 1,0 Pine extract 0.5 Poplar extract 0.5 Hyssop essential oil 0.1 Basil Essential Oil 0.1 Aristoflex 0.4 Gum 0.1 Lecithin 0.5 Glycerol 3.0 Epofen 0.1 Sharomiks 0.45 Water Rest

The gel form of the product with a high content of structured water, glycerin and a natural polysaccharide provides a moisturizing effect on the skin, increasing its moisture-holding qualities. Gums (guar or xanthan gum) have immunomodulating and sorbing properties, therefore they strengthen local immunity, and also bind polluting and toxic substances. The complex of highly effective substances from monarda, pine, poplar and hyssop has an antimicrobial, fungicidal and virucidal effect. Thus, the proposed composition has an immunostimulating effect (in particular, monarda essential oil affects B-lymphocytes, and T-lymphocytes - EM hyssop officinalis) and positively affects the general condition of the body by normalizing skin microbiocenosis by limiting the growth of fungi and pathogenic bacteria .

Example 2. Composition for the safe treatment of hands and other parts of the body, including intimate ones, their cleansing, moisturizing and deodorization through exposure to the active components of the gel, namely glycerin, gum, extracts of medicinal plants. The gel can be applied by applying to the surface of the skin when spraying spray forms or applying gel forms.

The composition contains oil, water-alcohol extracts and monarda essential oil, propylene glycol extracts of calendula, linden, grapefruit, hyssop and rose essential oils, aristoflex, lecithin, glycerin, epofen, charomix in the following ratio, wt.%:

Monarda Oil Extract 0.5 Hydroalcoholic extract of monarda 1,5 Monarda essential oil 0.1 Calendula Propylene Glycol Extract 1,0 Propylene Glycolic Linden Extract 1,0 Grapefruit essential oil 0.2 Hyssop essential oil 0.01 Rose essential oil 0.01 Aristoflex 0.3 Lecithin 0.2 Glycerol 1,0 Epofen 0.05 Sharomiks 0.5 Water Rest

Example 3. Composition for disinfection of rooms: rooms, offices, salons of vehicles, medical and cosmetic institutions; instruments, tools and other accessories. Processing of premises is carried out using spray forms of packaging of finished forms. Fine spraying provides the formation of a suspension of microdrops that bind, precipitate and neutralize dust particles and microorganisms from the air, while capturing the surfaces of furniture and equipment. Contact with the skin and mucous membranes of humans and animals is absolutely harmless. Tools can be sprayed or wiped with swabs moistened with the composition.

The composition contains oil and water-alcohol extracts and monarda essential oil, propylene glycol extracts from pine and cornflower, essential oils of grapefruit and rosemary, aristoflex and gum, glycerin, epofen, charomix in the following ratio of components, wt.%:

Monarda Oil Extract 0.7 Hydroalcoholic extract of monarda 0.5 Monarl essential oil 0.05 Propylene glycol pine extract 1,0 Cornflower propylene glycol extract 0.5 Grapefruit essential oil 0.1 Rosemary Essential Oil 0.1 Aristoflex 0.4 Gum 0.2 Glycerol 1,5 Epofen 0.003 Sharomiks 0.4 Water Rest

The composition in the form of a gel, spray provides ease of use. The gel can be prepared in various degrees of viscosity. The product moisturizes and softens the skin, prevents microbial infection and thrush.

The proposed composition having a fungicidal, antibacterial, virucidal effect, with a complex of fractions from Monarda fistulosa with plant extracts, sorbents and antioxidants can be presented in the form of gels, balms, creams and lotions, as sprays, liquids and in other forms.

To determine the active concentrations, the activity of individual fractions of monarda, which were purchased in the form of finished commodity forms as raw materials in the manufacture of the proposed compositions, was initially investigated. The antimicrobial properties of EM monarda were determined using the method of saturating the atmosphere with EM vapor at a concentration of from 0.47 to 236 μg / cm ³ on the following pathogenic and conditionally pathogenic microorganisms isolated in patients with inflammatory lesions of the skin, respiratory tract and intestines: Staphylococcus aureus, E .coli, Klebsiella pneumoniae, Streptococcus pyogenes, Pseudomonas aeruginosa, Candida albicans. Such a set of microorganisms is considered mandatory as standard. Essential oils of sage and tea tree, known for their bactericidal action, were used as the comparison preparations. The results are presented in the drawing.

It was found that microorganisms exhibit different sensitivity to the action of various essential oils. The bactericidal effect of monarda essential oil is realized in very low concentrations: at a concentration of 4.7 μg / cm ^3, there is a complete suppression of the growth of Staphylococcus aureus, E. coli, Klebsiella pneumoniae, Streptococcus pyogenes, Candida albicans, and at a concentration of 0.94 μg / cm ³ there is significant inhibition of the growth of all cultures.

These results are 25 times higher than the effect of tea tree essential oil (a similar result was observed at a concentration of 118 μg / cm ³ ) and clary sage - 50 times (236 μg / cm ³ ).

In the process of research it was found that Pseudomonas aeruginosa showed resistance to the effects of all used EM: only inhibition of its growth was observed at the used concentrations. The most sensitive cultures are Staphylococcus aureus and Streptococcus pyogenes.

Subsequent studies have shown that it is better to use essential oils in the form of aqueous suspensions and emulsions, which makes it possible to optimize their use.

Studies of the antiviral properties of EM monarda were carried out on a model system — on bacteriophages (bacterial viruses) of various morphotypes. In order to achieve an optimally uniform distribution of essential oils of both monarda and other plants, they were used in the form of microemulsions introduced into the gel. The studies were twofold: 1 - obtaining a forecast on the effect of EM on viral particles; 2 - the study of the synergism of essential oils and bacteriophages.

A pronounced antiviral activity of the gel with microemulsion EM monarda (0.1%) in vitro was detected. The virulent property of EM monarda manifested itself in a 100-fold decrease in the titer of lytic activity of all the investigated phages. Electron microscopy revealed a significant number of phages with morphological abnormalities: destruction of the phage head membrane was observed with a characteristic exit of the nucleic acid molecule, while the phage process retained its structure. The results obtained suggest that the effect of EM monarda is directed to the membrane apparatus of viral particles, the destruction of which leads to inactivation of the virus. It was noted that EM lavender does not have antiphase activity. None of the studied models (bacteriophages of various morphotypes) showed a decrease in the titer of lytic activity of phages. By electron microscopy, no evidence of a violation of the phage structure was revealed. Preservation of the ability of phages to adhere to the surface of bacterial cells was found. A study of the activity of EM of clary sage, peppermint and tea tree showed that the suppression of the viability of phage particles is observed with a significant increase in the concentration of EM microemulsion: for tea tree, this concentration is from 50 to 150 mg / ml, for mint - from 1 g / ml, for sage - from 2.0 to 2.5 g / ml.

Thus, EM monarda is active against bacteria, fungi (Candida albicans) and viral particles. The study of the properties of oil and alcohol extracts of monarda was carried out by standard microbiological methods. It was shown that the bactericidal activity in EM is most pronounced, which is explained by the high content of phenolic derivatives - thymol (up to 48%) and carvacrol (up to 19%).

Monarda extracts are used to improve the quality of a number of finished product preparations. Monarda alcohol extract is used as an auxiliary component for a drug substance; to reduce microbial contamination and improve taste in food products. When determining the effectiveness of finished compositions with CEM, the entire spectrum of their action was taken into account. For example, when examining a composition for disinfecting air and surfaces in rooms (according to the normative documentation “Methods of testing disinfectants to assess their safety and effectiveness.” M., 1998), the following results were obtained, shown in the table. As a test culture used Staphylococcus aureus.

The concentration of microorganisms in the flush Efficiency% Control surfaces Test surfaces (Staphylococcus aureus, pcs. 56, 2 × 10 ⁹ μl) 2.15 × 10 ⁹ 1.08 × 10 ⁶ 99.95% 1.9 × 10 ⁹ E. coli, pcs. 3E, 2.5 × 10 ⁹ , 32.08 × 10 ⁶ 92.4% 2.3 × 10 ⁹ Str. pyogenes, pcs. HR6, 2 × 10 ⁹ μl) 73.7 × 10 ⁶ 88.5%

Data confirm the effectiveness of the proposed composition against staphylococcus, E. coli and streptococcus.

For the first time, the activity of the composition with CEM against mold fungi was determined, including Aspirgilus niger. For this, various methods for determining fungicide on liquid and solid nutrient media were used, for example, or the composition was introduced into test tubes with broth and inoculated with gray mold, or a piece of special material was applied to a fresh grass lawn and impregnated with the composition according to Example 1 so that the final concentration the active principle was 0.03 mg / cm ³ . It was found that with this ratio there is a complete suppression of the growth of Aspirgilus niger.

Claims (3)

1. The composition has a fungicidal, antimicrobial and virucidal effect, characterized in that it contains as a base oil, water-alcohol extracts and essential oil of Monarda fistulosa, propylene-glycolic extracts of pine and poplar, essential oils of mint, basil , aristoflex, gum, lecithin, glycerin, epofen, charomix (propylene glycol solution of methyl and propyl esters of para-hydroxybenzoic acid) and water in the following ratio of components, wt.%:
monarda oil extract 0.5-3.0 hydroalcoholic extract of monarda 0.1-2.0 monarda essential oil 0.03-1.0 propylene glycol pine extract 0.5-1.0 propylene glycol poplar extract 0.5-1.0 peppermint essential oil 0.05-0.2 basil essential oil 0.07-0.1 aristoflex 0.2-1.0 gum 0.01-0.9 lecithin 0.1-7.0 glycerol 1.0-5.0 epofen 0.001-0.1 sharomiks 0.001-0.5 water rest 2. A composition having a fungicidal, antimicrobial and virucidal effect, characterized in that it contains oil, water-alcohol extracts and monarda essential oil (Monarda fistulosa), propylene glycol extracts of calendula, linden, grapefruit, hyssop and rose essential oils, aristoflex, lecithin, glycerin, epofen, charomix and water in the following ratio of components, wt.%:
monarda oil extract 0.5-1.5 hydroalcoholic extract of monarda 0.1-1.5 monarda essential oil 0.1-0.3 Calendula propylene glycol extract 0.5-1.0 propylene glycolic linden extract 0.5-1.0 grapefruit essential oil 0.05-0.2 hyssop essential oil 0.01-0.02 rose essential oil 0.01-0.05 aristoflex 0.2-1.0 lecithin 0.1-5.0 epofen 0.001-0.1 glycerol 1.0-5.0 sharomiks 0.5-0.8 water rest 3. A composition having a fungicidal, antimicrobial and virucidal effect, characterized in that it contains as a base oil, water-alcohol extracts and monarda essential oil (Monarda fistulosa), propylene glycol extracts from pine and cornflower, grapefruit and rosemary essential oils , aristoflex, gum, glycerin, epofen, charomix and water in the following ratio of components, wt.%:
monarda oil extract 0.05-0.7 hydroalcoholic extract of monarda 0.05-0.5 monarda essential oil 0.01-0.1 propylene glycol pine extract 0.5-1.0 propylene glycol cornflower extract 0.5-1.0 grapefruit essential oil 0.05-0.2 rosemary essential oil 0.05-0.1 aristoflex 0.2-1.0 gum 0.1-0.5 glycerol 1.0-5.0 epofen 0.001-0.1 sharomiks 0.4-0.6 water rest

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