RU2647460C1 - Active biological substance "clorophylliptum active plus", received on its basis of local action preparation and packaging fot it - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine, namely to an active biological or pharmaceutical substance. Substance is characterized by the presence of: an eucalyptus extract, benzalkonium chloride and essential eucalyptus oils, mint, fir, pine, lavender, tea tree, rosemary, coriander, rose and wormwood at the following ratio of components, mass%: eucalyptus extract – 18.86–55.63, benzalkonium chloride – 18.86–44.47, essential eucalyptus oil – 3.70–22.24, mint essential oil – 3.70–22.24, fir essential oil – 0.1–4.42, pine essential oil – 0.1–4.42, lavender essential oil – 0.1–4.42, tea tree essential oil – 0.1–4.42, rosemary essential oil – 0.1–4.42, coriander essential oil – 0.1–4.42, rose essential oil – 1.34–2.24, wormwood essential oil – 1.34–2.24.

EFFECT: substances and local action preparation on its basis have antibacterial activity, have bactericidal, bacteriostatic and antifungal effects.

9 cl, 4 tbl

Description

The scope of the invention

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

The invention also relates to a topical preparation 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 suppress the growth activity of the strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Basilius subtilis ATCC 6633 and Candida aibicans 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 antimicrobial agents requires the need to expand the arsenal of topical drugs that have antimicrobial effects, which are synthetic and semi-synthetic antibiotics, to 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 include antiseptics 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, 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 that include herbal components (eucalyptus, mint, sage and others). As a result, herbal preparations contain complexes of biologically active substances that are close to the metabolites of the body and are 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. These 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 well-known drug “Chlorophyllipt” (Clorophylliptum), which is obtained from the leaves of ball eucalyptus (Eucalyptus globulus L) or rod eucalyptus (Eucaliptus viminalis. L) by extraction with 95% ethanol, which has antibacterial activity against staphylococcus, streptococcus and cm. Auth. SU No. 1123706). In practice, 0.25%, 1% alcohol and 2% oil solutions of Chlorophyllipt are used. The main biologically active substances of the drug are lipophilic substances: a mixture of euglobals (phenolaldehydes), terpenoids and chlorophylls (Kurkin VA, Pharmacognosy, Samara, LLC Etching, 2004, pp. 327-333).

A solution of “Chlorophyllipt” (see Auth. Certificate, see SU No. 801341) is obtained by extraction of the leaves of eucalyptus rod (Eucaliptus viminalis. L) with 96% ethanol and subsequent treatment of the concentrated extract with a salt of divalent copper, namely 4% solution of copper sulfate with the subsequent extraction of the target product is the amount of hydrophobic components. Extraction with benzene is carried out three times with stirring each time for 15 minutes and settling for 5-6 hours. The settled benzene extract is washed 3 times with purified water and evaporated in vacuo at a temperature of 40 ° C, and then dissolved in alcohol or in oil.

Other methods for the preparation of “Chlorophyllipt” and preparations made on its basis are also known (see No. SU 1123706, RU 2320360, RU 2416423, UA 39463, UA 79383 and UA 92308).

The disadvantage of “Chlorophyllipt” and preparations made on its basis is that its antimicrobial effect is directed mainly to bacteria of the genus Staphylococcus and cannot be used against fungi. For example, table No. 1 shows the diameter of growth retardation of 1% of chlorophyllipt extract.

The essence of the invention

The objective of the invention is the creation of an active biological substance that has antibacterial activity, has bactericidal, bacteriostatic and antifungal effects.

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 bactericidal, bacteriostatic and antifungal effects.

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, Basillus 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, based on it, a locally produced preparation.

Another objective of the invention is to reduce the toxicity of exposure to the body during its use.

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

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

The above objectives are achieved by creating an active biological substance, which is characterized by the presence of an extract of eucalyptus, benzalkonium chloride and essential oils of eucalyptus, mint, fir, pine, lavender, tea tree, rosemary, coriander, rose and wormwood in the following ratio of components, wt. %:

eucalyptus extract 18.86-55.63 benzalkonium chloride 18.86-44.47 essential eucalyptus oil 3.70-22.24 peppermint essential oil 3.70-22.24 fir essential oil 0.1-4.42 pine essential oil 0.1-4.42 lavender essential oil 0.1-4.42 tea tree essential oil 0.1-4.42 rosemary essential oil 0.1-4.42 coriander essential oil 0.1-4.42 rose essential oil 1.34-2.24 wormwood essential oil 1.34-2.24

Also according to the invention, the above active biological substance additionally contains 1-15% polyvinylpyrrolidone.

Also according to the invention, the above active biological substance additionally contains 10-50% polysorbate 80.

Also according to the invention, the preferred composition of the above active biological substance has in the following ratio of components, wt. %:

eucalyptus extract 10.3 benzalkonium chloride 10.3 essential eucalyptus oil 5.15 peppermint essential oil 5.15 fir essential oil 1,03 pine essential oil 1,03 lavender essential oil 1,03 tea tree essential oil 1,03 rosemary essential oil 1,03 coriander essential oil 1,03 rose essential oil 0.51 wormwood essential oil 0.51 polysorbate 80 52.41 polyvinylpyrrolidone 10.3

Not intending to associate themselves with any particular theory, the inventors believe that the combination of the active components of the extract of eucalyptus, benzalkonium chloride and a complex of essential oils in an active biological substance provides a synergistic pharmacological effect, as a result of which the use of the obtained active biological substance leads to a suppression of activity growth strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Basillus subtilis ATCC 6633 and Candida aibicans ATCC 653/885. The resulting active biological substance has antibacterial activity, has bactericidal, bacteriostatic and antifungal effects.

The use of polyvinylpyrrolidone in an active biological substance 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 .

The use of polysorbate 80 in the active biological substance leads to the fact that the stability of the solution is increased.

A topical preparation is characterized in that it contains an active biological substance, according to the invention, glycerin and purified water in the following ratio of components, wt.%:

active biological substance 0.5-2 glycerol 0.5-5.0 purified water rest

Packing a topical preparation. According to the invention, a topical preparation is placed in a bottle with a metering device.

Example No. 1

To prepare an active biological substance, the active components are mixed: eucalyptus extract, benzalkonium chloride and essential oils of eucalyptus, mint, fir, pine, lavender, tea tree, rosemary, coriander, rose and wormwood, and with the addition of additional components of polyvinylpyrrolidone and polysorbate 80.

Table 2 shows the three obtained samples of the active biological substance that suppress the growth activity of the strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Basillus subtilis ATCC 6633 and Candida aibicans ATCC 6633 653 .

Peppermint oil was used as peppermint oil.

The obtained samples of the active biological substance have a color from green to greenish-brown, an shelf life of 36 months, and have an antibacterial and antifungal effect.

Example No. 2

Based on the obtained sample No. 3 of an active biological substance (see example No. 1), a topical preparation was obtained, for which purified water was mixed with glycerin, followed by the addition of an active biological substance (sample No. 3), as a result, three samples of a local action preparation were obtained (see table No. 3).

After that, the determination of the antibacterial and antifungal activity of the obtained sample No. 3 "Chlorophyllipt asset plus" was carried out. To compare the results, we took a control drug - Chlorophyllipt spray, which was manufactured by GNTsLS (State Scientific Center for Medicines).

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. For research, Muller-Hinton agar was used (Production - India “HIMediaLaboratorles Pvt. Ltd India”, the shelf life of the medium is until XI.2016). Saburo agar was used for Candidaalbicans (Production - India, “HIMediaLaboratorles Pvt. Ltd India”; the shelf life of the medium is until 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 used a "hungry" un seeded medium (agar-agar, water, salt). 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 are installed horizontally. Around the cylinders is poured the upper layer, consisting of a nutrient agarized medium, molten and cooled to 40 ° C, into which the corresponding standard of the daily culture of test strains was introduced. In advance, the top layer was well mixed until a homogeneous mass was formed. After solidification, the cylinders were pulled out with sterile tweezers, and the test preparations (Chlorophyllipt, manufactured by GNTSLS (patent RU 39463) and sample No. 3 “Chlorophyllipt asset plus”) were taken into the wells formed taking into account its 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 delay zone of up to 10 mm, indicates that the strains are not sensitive to the local preparation introduced into the well of the studied drug;

- 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. 4.

The data in table No. 4 indicate that, in contrast to the well-known drug, the invention actively suppresses the growth of the strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Basillus subtilis ATCC 6633, and also carries out static suppression of the growth of the fungus strain Candida aibicans ATCC 653 / 885, that is, the obtained local preparation, obtained on the basis of a biologically active substance, has antibacterial activity, has bactericidal, bacteriostatic and antifungal effects.

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

From the data in table No. 4 it is seen that the concentration of the active biological substance of 0.97% in the local preparation indicates the high efficiency of the active biological substance and that its use does not lead to irritation, which causes a high concentration of ethyl alcohol in the well-known drug "Chlorophyllipt", 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 ny ways.

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

We, the inventors of the obtained active biological substance, which has antibacterial activity, has bactericidal, bacteriostatic and antifungal effects, called: lat. "Clorophylliptum active plus", Ukrainian Chlorophyllipt Asset Plus, Rus. "Chlorophyllipt 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 understood that an active biological substance can be used as an antiseptic for scratches and burns.

Technical result

The technical result of the invention is the production of an active biological substance and a local preparation based on it, which have antibacterial activity, have bactericidal, bacteriostatic and antifungal effects.

Claims (12)

1. An active biological substance with antibacterial activity and antifungal activity, characterized by the presence of: eucalyptus extract, benzalkonium chloride and essential oils of eucalyptus, mint, fir, pine, lavender, tea tree, rosemary, coriander, rose and wormwood in the following ratio of components, wt .%: eucalyptus extract 18.86-55.63 benzalkonium chloride 18.86-44.47 essential eucalyptus oil 3.70-22.24 peppermint essential oil 3.70-22.24 fir essential oil 0.1-4.42 pine essential oil 0.1-4.42 lavender essential oil 0.1-4.42 tea tree essential oil 0.1-4.42 rosemary essential oil 0.1-4.42 coriander essential oil 0.1-4.42 rose essential oil 1.34-2.24 wormwood essential oil 1.34-2.24 2. The substance according to claim 1, which additionally contains 1-15% polyvinylpyrrolidone. 3. The substance according to any one of the above paragraphs. 1 or 2, which additionally contains 10-61.6% polysorbate 80. 4. Active biological substance with antibacterial activity and antifungal activity, characterized by the presence of: eucalyptus extract, benzalkonium chloride and essential oils of eucalyptus, mint, fir, pine, lavender, tea tree, rosemary, coriander, rose and wormwood, as well as the presence of polysorbate 80 and polyvinylpyrrolidone in the following ratio of components, wt.%: eucalyptus extract 10.3 benzalkonium chloride 10.3 essential eucalyptus oil 5.15 peppermint essential oil 5.15 fir essential oil 1,03 pine essential oil 1,03 lavender essential oil 1,03 tea tree essential oil 1,03 rosemary essential oil 1,03 coriander essential oil 1,03 rose essential oil 0.51 wormwood essential oil 0.51 polysorbate 80 51.60 polyvinylpyrrolidone 10.3 5. The substance according to claim 1, characterized in that it is used to suppress the activity of growth of strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Basillus subtilis ATCC 6633 and ATCC 65/885 . 6. A topical preparation with antibacterial activity and antifungal activity, characterized in that it contains an active biological substance, characterized according to any one of the above paragraphs. 1-5, glycerin and purified water in the following ratio of components, wt.%: active biological substance 0.5-2 glycerol 0.5-5.0 purified water rest 7. The drug according to claim 6, which is used to deodorize the oral cavity. 8. The drug according to claim 6, which is used for the prevention and treatment of infectious and inflammatory diseases of the upper respiratory tract. 9. The drug according to claim 6, placed in a bottle with a metering device.