WO2018084824A1

WO2018084824A1 - Topical preparation "ingaliptum active plus"

Info

Publication number: WO2018084824A1
Application number: PCT/UA2017/000095
Authority: WO
Inventors: Вадим Александрович САФОНОВ; Elena Yuriyivna GOLIK; Николай Андреевич КОМИСАРЕНКО; Андрей Николаевич КОМИСАРЕНКО; Дарья Валентиновна НИКОЛОВА; Дмитрий Иванович ИСАЕВ; Дмитрий Михайлович КОЖУШКО
Original assignee: Вадим Александрович САФОНОВ
Priority date: 2016-11-04
Filing date: 2017-10-10
Publication date: 2018-05-11
Also published as: RU2639562C1; UA117523C2

Abstract

The claimed invention relates to an active biological substance which exhibits antibacterial and antifungal activity, and a preparation based on same. The active biological substance is characterized by the following ratio of ingredients:26.5-63 wt% polysorbate 80; 3-12.45 wt% benzalkonium chloride; 2-18 wt% thymol; 2-18 wt% mint oil; 0.9-7.5 eucalyptus extract.

Description

INHALIPT ACTIVE PLUS

The field of application 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, 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, Basillus 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

An 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 use synthetic and semi-synthetic antibiotics, which are resistant to most microorganisms. , these antimicrobial agents have a toxic effect on organs and systems of the human and animal body, contribute to the development of disbac theriosis, 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, is a possible cause of adverse reactions, especially in children, pregnant women, women during lactation and patients with chronic diseases. In this regard, herbal preparations that are topical preparations are becoming more common and 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 biologically compatible with them. Another advantage of topical preparations of "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 well-known local drug "Ingalipt" or lat. "Ingaliptum", which was introduced in 1968 (see Order of the USSR Ministry of Health of 08.21.1969 Ns612 "On authorizing the medical use of medicines", also see Pharmacopoeia article "Ingaliptum" Ns FS 42-1000-86, publ. June 27, 1986).

The well-known local drug "Ingalipt" has the following composition, in May. %:

soluble streptocide 2,475

sodium sulfathiazole (norsulfazole sodium) 2.475 thymol 0.0495

eucalyptus oil 0.0495

peppermint oil 0.0495

ethanol 96% 6

refined sugar 5 glycerin 7

polysorbate-80 3

other purified water

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 not desirable for pregnant women, women during lactation, children and people while driving and performing types of work that require concentration.

Another disadvantage of the known drug is the undesirable use of sugar, which leads to an increase in blood glucose and 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 an active biological substance that has antibacterial activity, has bactericidal, bacteriostatic and antifungal effects.

5 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 objective of the invention is to suppress the growth activity of the following 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 15 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, on its 20 basis, a locally produced preparation.

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 means for suppressing the growth activity of strains: Staphylococcus aureus ATCC 25 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 claimed invention will be disclosed below as the description and tables,

z The above objectives are achieved by creating an active biological substance, which is characterized by the presence of thymol, eucalyptus oil, peppermint oil, eucalyptus extract, polysorbate 80, benzalkonium chloride in the following ratio, May. %:

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 an active biological substance provides a synergistic pharmacological effect, as a result of which the use of the obtained active biological substance inhibits 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. The resulting active biological substance has antibacterial activity, has bactericidal, bacteriostatic and antifungal effects.

According to an embodiment of the invention, the active biological 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, characterized in that it contains an active biological substance according to the invention, glycerin and purified water in the following ratio, May. %

active biological substance 0.21-0.63 glycerol 0.5-5.0 purified water A package of a topical preparation according to the invention is a topical preparation that is placed in a bottle with a metering device. Example Ns1

To prepare an active biological 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. After which the resulting solutions are mixed and receive an active biological substance.

Table Ns1 shows three samples of the obtained active biological substance that exhibit the activity of suppressing the growth of strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636, Pseudomonas aeruginosa ATCC 27853, Basillus subtilis ATCC 66335888 Candida.

Peppermint oil was used as peppermint oil.

Nsl table

The resulting substances have a green color, shelf life of 36 months, and have antibacterial and antifungal effects. Ns2 example

Based on the obtained sample of Ns3 of an active biological substance, see Example Nsl, a local preparation was prepared, for which purified water was mixed with glycerin, followed by the addition of an active biological substance (sample Νδ3), as a result of which a local preparation of the following composition was obtained, in May. %:

active biological substance 0.42

glycerin 2.75

purified water 96.83

After that, the antibacterial and antifungal activity of the obtained sample Ν-3 "Ingalipt Asset Plus" was determined. To compare the results, we took a control drug - a well-known local drug Ingalipt, which was made by different plants: Ingalipt Zdorovye Plant, Ingalipt with chamomile Zdorovye Plant, Ingalipt Aerosol JSC Stoma, Ingalipt Plant Microfarm and the resulting sample Na3 , which is obtained on the basis of the active biological 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 the work. For research, Muller-Hinton agar was used (Production - India “HIMediaLaboratorles Pvt. Ltd lndia”, the shelf life of the medium is until XI.2016). Saburo agar was used for Candidaalbicans (Production - India, "HIMediaLaboratorles Pvt. Ltd lndia" expiration date of Wednesday 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 5 two layers of a dense nutrient medium, poured into 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 "hole" are installed horizontally. Around the cylinders is poured the top 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 top layer was well mixed until a homogeneous mass was formed. After solidification, the cylinders were pulled out with sterile forceps, and in

Fifteen wells were placed in the test preparations (Ingalipt Plant Health, Ingalipt with chamomile Plant Health, Ingalipt Aerosol JSC Stoma, Ingalipt Plant Microfarm and sample Ne3 Ingalipt Asset Plus) taking into account its volume (0.3 ml).

The volume of medium for the top layer ranged from 14 to 16 ml. Cups

20 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 inhibition of the strains around the well, as well as zones of 25 delays of up to 10 mm, indicates that the strains are not sensitive to the local drug 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;

zo - growth inhibition zones with a diameter of 15–25 mm are regarded as an indicator of the sensitivity of the strains to a local drug; θ

- 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 out in table Ν ° 2. Table Ns2

The data in table Ns2 indicate that, in contrast to known preparations, the invention actively suppresses the growth of the strains: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Basillus subtilis ATCC 6633, and also provides static suppression of the growth of the fungus strain Candida albicans ATCC 653/885 . That is, the resulting topical 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 additionally provides 5 deodorization of the oral cavity.

From the data presented in table Ns2, it can be seen that the concentration of the active biological substance of 0.42% in a topical preparation indicates the high effectiveness 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 "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 x ways.

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

A package of a topical preparation is the resulting topical preparation, which is placed in a bottle with a dosing device, with the help of which the topical preparation

20 is applied to the oral cavity.

Title to the invention

We are the inventors of the obtained active biological substance, which has antibacterial activity, has 25 bactericidal, bacteriostatic and antifungal effects called: lat. "Lngaliptum active plus", Ukrainian “1ngalt 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 an active biological substance can be used as an antiseptic for scratches and burns.

Technical result

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

Claims

CLAIM

1. An active biological substance with antibacterial activity and antifungal activity, characterized by the presence of: thymol, eucalyptus oil, peppermint oil, extract

5 eucalyptus, polysorbate 80, benzalkonium chloride in the following ratio, May. %:

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.

Yu

3. The substance according to claim 2, which has a predominant composition in the following ratio of components, May. %:

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. The substance according to claim 1, characterized in that it is used to suppress the activity of growth of strains: Staphylococcus aureus ATCC

15 25923, Escherichia coli ATCC 25922, Proteus vulgaris ATCC 4636,

Pseudomonas aeruginosa ATCC 27853, Basillus subtilis ATCC 6633, and Candida albicans ATCC 653/885.

5. A topical preparation with antibacterial activity and antifungal action, characterized

20 in that it contains an active biological substance, characterized by any of the above 1-4, glycerin and purified water in the following ratio, May. %:

active biological substance 0.21-0.63

glycerin 0.5-5.0

purified water

5 6. The drug according to claim 5, which is used to deodorize the oral cavity.

7. The drug according to claim 5, which is used for the prevention and treatment of infectious and inflammatory diseases of the upper respiratory tract.

S 8. The drug according to claim 5, which is placed in a bottle with a metering device.