RU2639562C1 - Active biological substance "ingaliptum active plus", local action preparation obtained on its basis - Google Patents

Abstract

FIELD: pharmacology.SUBSTANCE: invention relates to a biologically active substance for inhibition of the growth activity of Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633 and Candida albicans ATCC 653/885 strains. The biologically active substance for inhibition of the growth activity of Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633 and Candida albicans ATCC 653/885 strains contains thymol, eucalyptus oil, peppermint oil, eucalyptus extract, polysorbate 80, benzalkonium chloride at a certain ratio of components. The local action preparation for inhibition of the growth activity of Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633 and Candida albicans ATCC 653/885 strains contains the biologically active substance, glycerin and purified water at a certain ratio of components. The above-described substance and preparation are effective for inhibition of the growth activity of Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633 and Candida albicans ATCC 653/885 strains.EFFECT: increased preparation efficiency.6 cl, 2 tbl, 2 ex

Description

The field of application of the invention

The claimed invention relates to an active biological or pharmaceutical substance, which has antibacterial activity, has a bactericidal, bacteriostatic and antifungal effect.

The invention also relates to a topical preparation, which is obtained on the basis of the above active biological substance.

The invention can be used for the prevention and treatment of infectious and inflammatory diseases.

Also, the invention can be used to deodorize the oral cavity.

The invention can also be used to inhibit the growth activity of the strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633 and Candida albicans ATCC 653/885.

The claimed invention can be used in the chemical, pharmaceutical, cosmetic and food industries.

Prior art

The increase in the number of infections caused by various kinds of microorganisms that are resistant to many antimicrobials requires the need to expand the arsenal of topical drugs that have antimicrobial effects, which are used synthetic and semi-synthetic antibiotics, which most microorganisms quickly develop resistance. In addition, these antimicrobial agents have a toxic effect on organs and systems of the human and animal body, contribute to the development of dysbiosis, hepatitis and the like.

The majority of local antimicrobials contain an antiseptic of chemical origin, but they are xenobiotics for the body and therefore, against the background of infectious intoxication, cause an additional load of its metabolizing and eliminated systems, and therefore are a possible cause of adverse reactions, especially in children, pregnant women, women during lactation and patients with chronic diseases. In this regard, herbal preparations are becoming more common, which are topical preparations and include herbal components (eucalyptus, mint, sage and others). As a result, phytopreparations contain complexes of biologically active substances that are close to the metabolites of the body and biologically compatible with them. Another advantage of topical preparations - “phytopreparations” - is their normalizing effect on altered body functions in the absence of influence on other indicators. The noted properties, as well as the use of low doses of plant components, can virtually eliminate toxic and side effects on the human body during their use.

The topical preparation "Ingalipt" or lat is widely known. "Ingaliptum", which was introduced in 1968 (see Order of the USSR Ministry of Health of 08.21.1969 No. 612 "On the permission of medical use of medicines", also see Pharmacopeia article "Ingaliptum" No. FS 42-1000-86, publ. 06/27/1986).

Known local drug "Ingalipt" has the following composition, wt.%:

Soluble streptocide 2,475 Sulfathiazole sodium (norsulfazole sodium) 2,475 Thymol 0,0495 Eucalyptus oil 0,0495 Peppermint oil 0,0495 Ethanol 96% 6 Rafinated sugar 5 Glycerol 7 Polysorbate-80 3 Purified water Rest

A well-known local drug has antiseptic and anti-inflammatory effects and is used for tonsillitis, pharyngitis, laryngitis, aphthous and ulcerative stomatitis.

However, the use of sulfanilamides — streptocide and norsulfazole sodium (hexahydrate) —in a well-known topical preparation, is not optimal, since sulfonamides are one of the oldest classes of antibacterial drugs. Over the past decades, they have lost their significance and have very limited indications for use. Sulfanilamides in activity are significantly inferior to modern antibiotics and at the same time are characterized by high toxicity and side effects. Most clinically significant bacteria are currently resistant to sulfonamides, and this reduces the effectiveness of using the known drug.

Another disadvantage of the known drug is the undesirable use of ethyl alcohol, which has an irritating effect on the inflamed mucosa of the oropharynx and nasopharynx, as well as its use is undesirable for pregnant women, women during lactation, children and people while driving and performing types of work that require concentration of attention.

Another disadvantage of the known drug is the undesirable use of sugar, which leads to an increase in blood glucose, and the drug cannot be used by people with diabetes. Also, during the use of a well-known local drug, the presence of sugar in its composition creates a favorable environment for the reproduction of bacteria, which leads to problems with teeth and gums.

Also a disadvantage of the known drug is that it does not have an antifungal effect.

The essence of the invention

The objective of the invention is the creation of a biologically active substance that has antibacterial activity, has a bactericidal, bacteriostatic and antifungal effect.

Another objective of the invention is the creation of a topical preparation, which is obtained on the basis of an active biological substance that has antibacterial activity, has a bactericidal, bacteriostatic and antifungal effect.

Another object of the invention is to suppress the growth activity of the strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633 and Candida albicans ATCC 653/885.

Another objective of the invention is to increase the effectiveness of the spectrum of action for the prevention and treatment of infectious and inflammatory diseases.

Another objective of the invention is to increase the effectiveness of the spectrum of action during deodorization of the oral cavity.

It is also an object of the invention to reduce the addiction (resistance) of microorganisms to an active biological substance and a topical preparation obtained on its basis.

Another objective of the claimed invention is to reduce the effects of toxicity on the body during its use.

Another objective of the invention is to expand the arsenal of agents for suppressing the growth activity of strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633 and Candida albicans ATCC 653/885.

Other objectives and advantages of the claimed invention will be disclosed below as the description and tables.

The above objectives are achieved by creating a biologically active substance, which is characterized in that it contains: thymol, eucalyptus oil, peppermint oil, eucalyptus extract, polysorbate 80, benzalkonium chloride in the following ratio, wt.%:

Polysorbate 80 26.5-63 Benzalkonium chloride 3-12.45 Thymol 2-18 Eucalyptus oil 2-18 Peppermint oil 2-18 Eucalyptus extract 0.9-7.5

Not intending to associate themselves with any particular theory, the inventors believe that the combination of active components in a biologically active substance provides a synergistic pharmacological effect, as a result of which the use of the obtained biologically active substance inhibits the growth activity of the strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633 and Candida albicans ATCC 653/885. The obtained biologically active substance has antibacterial activity, has a bactericidal, bacteriostatic and antifungal effect.

According to an embodiment of the invention, the biologically active substance further comprises 1-12% polyvinylpyrrolidone.

The use of polyvinylpyrrolidone leads to the prolongation of the antimicrobial and antifungal action, which consists in the fact that the presence of polyvinylpyrrolidone creates a film on the surface of the organ that is being processed, and this leads to improved adhesion, which leads to the prolongation of the antimicrobial and antifungal action.

A topical preparation is characterized in that it contains a biologically active substance, glycerin and purified water in the following ratio of components, wt.%:

Biologically active substance 0.21-0.63 Glycerol 0.5-5.0 Purified water rest

A package of a topical preparation according to the invention is a topical preparation which is placed in a bottle with a metering device.

Example 1

To prepare a biologically active substance, thymol is dissolved in a mixture of eucalyptus and peppermint oils. The polysobrate 80 (tween) and benzalkonium chloride are mixed in an eucalyptus extract. Then the resulting solutions are mixed and get a biologically active substance.

Table 1 shows three samples of the obtained biologically active substance that exhibit the activity of inhibiting the growth of strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633 AT 653 Candice albicans .

Peppermint oil was used as peppermint oil.

The resulting substances have a green color, shelf life of 36 months and have antibacterial and antifungal effects.

Example 2

Based on the obtained sample No. 3 of a biologically active substance, see example 1, a local preparation was obtained, for which purified water was mixed with glycerin, followed by the addition of a biologically active substance (sample No. 3), as a result, a local preparation of the following composition was obtained, wt.%:

Biologically active substance 0.42 Glycerol 2.75 Purified water 96.83

After that, the determination of the antibacterial and antifungal activity of the obtained sample No. 3 "Ingalipt asset plus" was carried out. To compare the results, we took a control drug - a well-known local drug, Ingalipt, which was made by different plants: Ingalipt of Zdorovye Plant, Ingalipt with chamomile of Zdorovye Plant, Ingalipt Aerosol of Stoma JSC, Ingalipt of Microfarm Plant and sample No. 3, which is obtained on the basis of the biologically active substance "Ingalipt asset plus".

A microbial suspension of strains (microorganisms) was prepared, which was carried out using a Densi-La-Meter device (manufactured by PLIVA-Lachema, Czech Republic; wavelength 540 nm). The microbial suspension of the strains was made according to the instructions that are attached to the device and the information letter about innovations in the healthcare system "Standardization of the preparation of microbial suspensions", Kiev. The culture of the strains was synchronized using a low temperature (4 ° C). Microbial loads were 10 ⁷ microbial cells per 1 ml of medium and were installed according to the McFarland standard. An 18-24-hour culture of microorganism strains was taken into work. Müller-Hinton agar (Production - India “HIMediaLaboratorles Pvt. Ltd. India”, shelf life of the medium until XI.2016) was used for research. Saburo agar was used for Candida albicans (Production - India, HIMediaLaboratorles Pvt. Ltd. India, shelf life until Wednesday, XI.2016).

The method of diffusion of the drug into agar was carried out by "wells". The determination of the activity of antibacterial drugs was carried out on two layers of a dense nutrient medium spilled in Petri dishes. In the lower layer, a "hungry" un seeded medium (agar-agar, water, salt) was used. The bottom layer is a substrate of 10 ml of "hungry agar", on which 3-6 thin-walled stainless steel cylinders with a diameter of 8 mm and a height of 10 mm "hole" are installed horizontally. Around the cylinders is poured the upper layer, consisting of a nutrient agar medium, molten and cooled to 40 ° C, into which the corresponding standard of the daily culture of test strains was introduced. In advance, the upper layer was well mixed until a homogeneous mass was formed. After solidification, the cylinders were pulled out with sterile tweezers and test preparations were placed in the resulting wells (Ingalipt Zdorovye Plant, Ingalipt with chamomile of Zdorovye Plant, Ingalipt Aerosol JSC Stoma, Ingalipt Plant Microfarm and sample No. 3 Ingalipt Asset Plus) taking into account their volume (0.3 ml).

The volume of medium for the upper layer ranged from 14 to 16 ml. The cups were dried for 30-40 minutes at room temperature and placed in a thermostat for 18-24 hours.

When evaluating the antimicrobial and antifungal properties of the drugs, the following criteria were used:

- the absence of zones of growth retardation of strains around the well, as well as a zone of delay of up to 10 mm, indicates that the strains are insensitive to the studied local drug introduced into the well;

- growth retardation zones with a diameter of 10-15 mm indicate a low sensitivity of the strains to a topical preparation;

- growth retardation zones with a diameter of 15-25 mm are regarded as an indicator of the sensitivity of the strains to a topical preparation;

- growth inhibition zones, the diameter of which exceeds 25 mm, indicates a high sensitivity of the strains to the drug local action.

To obtain reliable data to draw a conclusion regarding the effectiveness of the drugs, three independent trials were performed (number of repetitions of studies).

Test data of antibacterial and antifungal activity are set forth in table No. 2.

The data in table No. 2 indicate that, in contrast to the known drugs, the invention actively suppresses the growth of strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, and also provides static suppression of the growth of the fungus strain Candida albicans ATCC 653 / 885. That is, the resulting local preparation, obtained on the basis of a biologically active substance, has antibacterial activity, has a bactericidal, bacteriostatic and antifungal effect.

It should be further noted that the use of peppermint and eucalyptus oils additionally provides deodorization of the oral cavity.

From the data in table No. 2 it can be seen that the concentration of the biologically active substance of 0.42% in a topical preparation indicates the high effectiveness of the biologically active substance and that its use does not lead to irritation, which causes a high concentration of ethyl alcohol in the well-known drug "Ingalipt", and also suggests that the local drug can be effectively used against catarrh and for the prevention and treatment of infectious and inflammatory diseases of the upper respiratory tract s.

The resulting topical preparation can be used in the form of a solution, spray and aerosol.

A package of a topical preparation is an obtained topical preparation that is placed in a bottle with a dosing device, with which a topical preparation is applied to the oral cavity.

Title to the invention

The inventors obtained biologically active substance, which has antibacterial activity, has a bactericidal, bacteriostatic and antifungal effect, called: lat. "Ingaliptum active plus", Ukrainian Ingalipt Asset Plus, Rus. "Ingalipt asset plus."

It should be clear that this description provides the necessary and sufficient data for a clear and complete understanding of the invention. Information that is obvious to specialists in this field of technology and which would not contribute to a better understanding of the invention was not given in this description.

For example, it is clear that a biologically active substance can be used as an antiseptic for scratches and burns.

Technical result

The technical result of the invention is to obtain a biologically active substance and a topical preparation based on it, which have antibacterial activity, have bactericidal, bacteriostatic and antifungal effects.

Claims (9)

1. A biologically active substance for suppressing the growth activity of strains of Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633 and Candida albicans ATCC 653/8, which contains, eucalyptus, peppermint oil, eucalyptus extract, polysorbate 80, benzalkonium chloride in the following ratio, wt.%: Polysorbate 80 26.5-63 Benzalkonium chloride 3-12.45 Thymol 2-18 Eucalyptus oil 2-18 Peppermint oil 2-18 Eucalyptus extract 0.9-7.5 2. The substance according to claim 1, which additionally contains 1-12% polyvinylpyrrolidone. 3. The substance according to claim 2, which has a predominant composition in the following ratio of components, wt.%: Polysorbate 80 62.24 Benzalkonium chloride 12.45 Thymol 6.22 Eucalyptus oil 6.22 Peppermint oil 6.22 Eucalyptus extract 2,50 Polyvinylpyrrolidone 4.15 4. A topical preparation for suppressing the growth activity of the strains of Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Bacillus subtilis ATCC 6633 and Candida albicans ATCC 653/885, which contains a biologically active substance by pp. 1-3, glycerin and purified water in the following ratio of components, wt.%: Biologically active substance 0.21-0.63 Glycerol 0.5-5.0 Purified water Rest 5. The drug according to claim 4, which is used to deodorize the oral cavity. 6. The drug according to claim 4, which is used for the prevention and treatment of infectious and inflammatory diseases of the upper respiratory tract.