RU2790054C2 - Composition and method for control of infectious diseases with functional flavoring substances - Google Patents

Abstract

FIELD: pharmaceutical industry.

SUBSTANCE: group of inventions relates to the pharmaceutical industry, namely to a composition for inhibition of E. coli infection, methicillin-resistant staphylococcus aureus (hereinafter – MRSA), influenza virus, rhinovirus, or M. Tuberculosis. Composition (1) for inhibition of E. coli infection, MRSA, influenza virus, rhinovirus, or M. Tuberculosis contains: 0.25-7% of β-pinene, 0.25-25% of borneol, 5-30% of cinnamon aldehyde, 0.25-25% of citral, 0.25-5% of d-limonene, 1-10% of eucalyptol, 1-15% of eugenol, 10-30% of farnesol, 25-50% of linalool, 0.5-7% of thymol, and 2.7% of vanillin. Composition (2) for inhibition of E. coli infection, MRSA, influenza virus, rhinovirus, or M. Tuberculosis contains: 1-3% of β-pinene, 1-5% of borneol, 15-25% of cinnamon aldehyde, 1-3% of d-limonene, 5-10% of eucalyptol, 5-15% of eugenol, 25-50% of linalool, 0.5-2% of thymol, and 5-10% of vanillin. A method for inhibition of E. coli infection, MRSA, influenza virus, rhinovirus, or M. Tuberculosis includes administration of therapeutically effective amount of above-described composition (1) to a patient who needs it. A method for inhibition of E. coli infection, MRSA, influenza virus, rhinovirus, or M. Tuberculosis includes administration of therapeutically effective amount of above-described composition (2) to a patient who needs it.

EFFECT: above-described compositions and methods are effective for inhibition of E. coli infection, MRSA, influenza virus, rhinovirus, or M. Tuberculosis.

16 cl, 13 ex

Description

Field of invention

The present invention relates to a composition and method for controlling infectious diseases and, in particular, to a composition and method that include several different functional components.

Prior Art

Infectious diseases are a widespread and growing problem. Bacteria, viruses, fungi and parasites dominate the environment, including what is touched, what is drunk and eaten, even what is breathed. While many are harmless or even beneficial, there are some that are very harmful and cause infectious diseases that lead to sickness and death. Infectious diseases cause a third of all deaths in the world.

Infectious diseases affect all people globally and are especially dangerous among vulnerable populations, including populations in developing countries, the very young, the elderly, and people undergoing treatment for other medical conditions. Infectious diseases are of particular concern in hospitals and are common in nursing homes, leading to poor quality of life, susceptibility to other ailments, complications of existing conditions, and death.

Methicillin-resistant S. aureus (MRSA), antibiotic-resistant P. aeruginosa, and enterobacteria such as E. coli and K. pneumonia are among the most dangerous bacteria listed as a World Health Organization priority. health organization to develop new treatments. Antibiotics, the current standard of care for infectious diseases caused by bacteria, are becoming less effective as bacteria develop resistance to treatments through evolutionary mutations, such as producing secretions that destroy antibiotics, and changing structures in ways that prevent the antibiotic from being delivered or attached. .

Ways to defeat bacteria include inhibition of replication, inhibition of biofilm formation, and inhibition of quorum sensing. To inhibit the replication of bacteria, the antibacterial agent may interfere with the process by which bacteria develop and reproduce safely. To inhibit the formation of a biofilm of bacteria, the antibacterial agent may interfere with the processes by which bacteria adhere to each other or to other surfaces. To inhibit quorum sensing, an antibacterial agent can interfere with the processes by which bacteria transmit, receive, and respond to information.

Viruses such as norovirus, herpes virus, many types of influenza viruses and rhinoviruses are a continuing global health concern despite all current preventive measures. Influenza alone is estimated to cause 3 to 5 million infections and 300,000 to 650,000 deaths each year.

Ways to defeat viruses include inhibition of virus entry, inhibition of replication, and inhibition of budding and release. To inhibit the entry of the virus, the antiviral agent may interfere with the ability of the virus to infect a host cell by destroying ICAM-1 (Inter-Cellular Adhesion Molecule 1) or helicase. To reduce or prevent viral replication, the antiviral agent may interfere with the production or use of the polymerase or proteases. To prevent the release of virus progeny, the antiviral agent may interfere with the production or use of neuraminidase.

Fungi are responsible for many pathogenic infections. There are approximately 300 fungi that cause human diseases. Fungal infections can cause complications in patients treated for other diseases, can lead to serious illness, and can cause death.

Ways to defeat fungi or control fungal infections include inducing apoptosis and preventing or reducing the release of harmful toxins. To induce apoptosis, an antifungal agent can activate metacaspases, stimulate the production of reactive oxygen species, cause disruption of cellular ultrastructure, induce DNA fragmentation, and trigger externalization of phosphatidylserine. To reduce or prevent the biosynthesis of harmful toxins, the antifungal agent can down-regulate the expression of the toxin biosynthesis genes afIR, afIT, afID, aflM, and aflP.

Parasites such as P. falciparum are extremely dangerous and cause malaria, a disease that is estimated to cause over 212 million infections and over 400,000 deaths each year.

Ways to defeat parasites such as P. falciparum include interfering with the systems used to metabolize nutrients into energy and interfering with enzymatic functions. To interfere with metabolism, the antiparasitic agent may inhibit the biosynthesis of isoprenoids. To interfere with enzymatic functions, the antiparasitic agent may target key enzymes for inhibition, such as the plasmepsin II enzyme.

Tuberculosis is the leading cause of death from a single infectious agent. M. tuberculosis, the bacterium that causes the disease, is spread through the air by currently infected people when they cough, sneeze, or otherwise release infected fluids into the air. Tuberculosis caused over 1.6 million deaths and over 10 million illnesses in 2016, making it the ninth leading cause of death in the world.

Ways to defeat M. tuberculosis include direct inhibition of the pathogen and inhibition of biofilm formation and quorum sensing functions. For direct inhibition of M. tuberculosis, the antimicrobial agent can degrade the cell wall of the pathogen. To inhibit biofilm formation and quorum sensing functions, an antimicrobial agent can be targeted to genes and proteins involved in these functions.

Brief summary of the invention

The present invention is directed to a composition and method for combating the negative effects of microbial pathogens through a flavoring agent. A means is being contemplated for combining specific substances known to be generally recognized as safe (GRAS) for humans for use in flavoring agents for synergistic effects against microbes such as bacteria, viruses, fungi and parasites. The use of fragrance chemicals with these properties enables the use of many commonly used products, including soaps, lotions, detergents, shampoos, perfumes, body sprays, fabric softeners, and softener-antistatic wipes, as effective and safe antimicrobial delivery vehicles.

The present invention, in one form, relates to a composition comprising:

0.25-7% β-pinene,

0.25-25% borneol,

5-30% cinnamaldehyde,

0.25-25% citral,

0.25-5% d-limonene,

1-10% eucalyptol,

1-15% eugenol,

10-30% farnesol,

25-50% linalool,

0.5-7% thymol and

2-7% vanillin.

In one particular form of this composition, the components are as follows:

0.25-3% β-pinene,

0.25-25% borneol,

10-25% cinnamaldehyde,

0.25-5% citral,

0.25-5% d-limonene,

1-8% eucalyptol,

5-15% eugenol,

20-30% farnesol,

25-50% linalool,

0.5-7% thymol and

5-20% vanillin.

In an alternative form, this composition contains:

3-7% β-pinene,

1-5% borneol,

5-20% cinnamaldehyde,

1-5% citral,

1-5% d-limonene,

5-10% eucalyptol,

10-15% eugenol,

10-20% farnesol,

30-50% linalool,

2-7% thymol and

5-20% vanillin.

In yet another form, this composition contains:

0.5-5% β-pinene,

1-5% borneol,

10-30% cinnamaldehyde,

1-5% citral,

1-5% d-limonene,

1-5% eucalyptol,

1-7% eugenol,

20-25% farnesol,

25-50% linalool,

0.5-2% thymol and

2-7% vanillin.

In yet another form, this composition contains:

1-3% β-pinene,

1-5% borneol,

15-25% cinnamaldehyde,

1-3% d-limonene,

5-10% eucalyptol,

5-15% eugenol,

20-50% linalool,

0.5-2% thymol and

5-10% vanillin.

The present invention, in another form, relates to a method that treats or limits the occurrence of infectious diseases by administering a therapeutically effective amount of a composition comprising:

0.25-7% β-pinene,

0.25-25% borneol,

5-30% cinnamaldehyde,

0.25-25% citral,

0.25-5% d-limonene,

1-10% eucalyptol,

1-15% eugenol,

10-30% farnesol,

25-50% linalool,

0.5-7% thymol and

2-7% vanillin.

In one useful form, this method treats infectious diseases such as those caused by E, coli, MRSA, influenza virus, and rhinovirus.

In various alternative forms, a method of treating or limiting the occurrence of a limited number of infectious diseases includes administering any of the above compositions.

It is contemplated that the present compositions can be used for topical application to a patient or as a surface disinfectant. In addition, the compositions can be formulated to take advantage of the microbial properties of the component (ie flavoring chemicals) for administration to the auditory and respiratory systems, for example when formulated as a liquid or aerosol. The presence of these antimicrobial flavors in the nasal and respiratory tract provides sufficient sites for interaction with pathogens via the antimicrobial flavors and thereby control or eliminate infectious diseases.

In addition, the presently disclosed compositions can be formulated as a spray, aerosol, or other means of releasing these fragrances into the air to be a layer of protection against microbial infections through air-to-air contact with microbes to provide beneficial effects. and increased security.

In addition, the currently disclosed compositions can be formulated for use in a variety of applications, which include wide open areas of airports, hospitals, triage centers, rapid response centers, and biosecurity response structure locations to control the spread of severe epidemics caused by such pathogens, like the Ebola virus and the "Marburg disease" virus, through inhibition of protease, helicase and neuraminidase.

In addition, these compositions can be used in a variety of applications such as travel proximity spaces such as airports, aircraft, cruise ships, ports of entry, checkpoints and ports of departure to prevent or reduce the spread of tuberculosis.

Detailed description of the invention

The present invention is directed to unique compositions that contain several different components, many of which are classified as "flavoring substances". In one form, this composition has the following components in the following amounts:

0.25-7% β-pinene,

0.25-25% borneol,

5-30% cinnamaldehyde,

0.25-25% citral,

0.25-5% d-limonene,

1-10% eucalyptol,

1-15% eugenol,

10-30% farnesol,

25-50% linalool,

0.5-7% thymol and

2-7% vanillin.

In an alternative form, this composition has the following components:

0.25-3% β-pinene,

0.25-25% borneol,

10-25% cinnamaldehyde,

0.25-5% citral,

0.25-5% d-limonene,

1-8% eucalyptol,

5-15% eugenol,

20-30% farnesol,

25-50% linalool,

0.5-7% thymol and

5-20% vanillin.

In yet another form, this composition has the following components:

3-7% β-pinene,

1-5% borneol,

5-20% cinnamaldehyde,

1-5% citral,

1-5% d-limonene,

5-10% eucalyptol,

10-15% eugenol,

10-20% farnesol,

30-50% linalool,

2-7% thymol and

5-20% vanillin.

In yet another form, this composition has the following components:

0.5-5% β-pinene,

1-5% borneol,

10-30% cinnamaldehyde,

1-5% citral,

1-5% d-limonene,

1-5% eucalyptol,

1-7% eugenol,

20-25% farnesol,

25-50% linalool,

0.5-2% thymol and

2-7% vanillin.

In yet another form, this composition has the following components:

1-3% β-pinene,

1-5% borneol,

15-25% cinnamaldehyde,

1-3% d-limonene,

5-10% eucalyptol,

5-15% eugenol,

20-50% linalool,

0.5-2% thymol and

5-10% vanillin.

These compositions have unique antimicrobial and antiviral properties. These compositions can be made to treat or limit the occurrence of various diseases and to kill, and/or be used as a disinfectant against various microbes, pathogens and the like. For example, these compositions can be used to kill microbes as a disinfectant and to be administered to a patient to treat an appropriate disease or condition. This composition is effective against a variety of pathogens, including but not limited to E. coli, MRSA, influenza, rhinovirus, and M. tuberculosis.

These compositions can be formulated into various forms for use by the patient and can be used as a surface disinfectant. Accordingly, these compositions may be formulated as a spray or aerosol for surface application. In addition, these compositions may be formulated for topical application to a patient. In yet another form, these compositions may be in the form of a liquid or aerosol for ear or respiratory systems.

Examples

The following examples provide further understanding of the present compositions and their applications. These examples do not limit the scope of this disclosure in any way.

Example 1

Inhibition of bacterial quorum sensing is done by terpenes such as β-pipene, citral, d-limonene, and phenols such as vanillin, in ways such as inhibition of the AHL system as seen against bacterial species such as E. coli and P. putida, and phenols such as cinnamaldehyde and eugenol by binding to quorum sensing receptors such as RpfF, LuxS, LuxR, LasR, ExpL and ExpR as observed against bacterial species such as P. fluorescens, V. harveyiw P. aeruginosa.

Example 2

Inhibition of bacterial replication is carried out by terpenes such as citral, as has been observed against bacterial species such as C. sakazakii.

Example 3

Inhibition of bacterial biofilm formation is mediated by phenols such as cinnamaldehyde, eugenol, thymol, and vanillin, and also by terpenes such as citral, farnesol, and linalool, as observed against bacterial species such as C. sakazakii, S. pyogenes, S. aureus ( including methicillin-resistant strain), A. baumannii, S. saintpaul, S. enteritidis, E. coli, V. anguillarum, Vibrio spp. and V. vulnificus.

Example 4

Additionally, terpenes such as β-pinene, borneal, citral, d-limonene, farnesol and linolool as well as phenols such as eugenol, thymol and vanillin are effective against bacterial species such as E. coli, P. aeruginosa, P mirabilis, K. pneumoniae, A. baumannii, S. aureus, E. faecalis and B. subtilis.

Example 5

Inhibition of viral entry can be done by terpenes such as eucalyptol, which inhibits the ICAM-1 molecule, as seen against influenza virus-induced pneumonia.

Example 6

Inhibition of viral replication is carried out by terpenes such as β-pinene, borneol, citral, d-limonene, and also phenols such as cinnamaldehyde and eugenol, as observed against viral pathogens such as HSV-1 (herpes simplex virus-1), influenza A/PR/8 virus, influenza A virus, yellow fever, MNV-1 (simulating human norovirus).

Example 7

Inhibition of the release of virus progeny is carried out by phenols such as vanillin, which inhibit the enzyme neuraminidase.

Example 8

Induction of fungal apoptosis is mediated by activation of metacaspases, production of reactive oxygen species, inducing disruption of cellular ultrastructure, inducing DNA fragmentation, and triggering externalization of phosphatidylserine by terpenes such as farnesol and linalool, as seen against fungi such as P. expansum.

Example 9

Inhibition of the biosynthesis of harmful toxins by fungi is mediated by downregulation of the expression of the toxin biosynthesis genes afIR, afIT, afID, aflM and aflP by phenols such as cinnamaldehyde and eugenol, and also by terpenes such as citral and farnesol against fungi such as A. flavus.

Example 10

Interference with the metabolic systems of parasites by preventing or reducing isoprenoid biosynthesis is carried out by terpenes such as d-limonene, farnesol and linalool, as has been observed against the parasite P. falciparum.

Example 11

Interference with enzymatic functions of parasites by targeting enzymes such as the flamepsin II enzyme is mediated by phenols such as thymol against the parasite P. falciparum.

Example 12

Direct inhibition of M. tuberculosis through cell wall degradation of M. tuberculosis is carried out by terpenes such as β-pinene, d-limonene and linalool, as well as phenols such as cinnamaldehyde, eugenol and thymol.

Example 13

Inhibition of biofilm and quorum sensing functions by targeting LuxR-like genes and M. tuberculosis proteins can be mediated by terpenes such as β-pipene, d-limonene, and linalool, as well as phenols such as cinnamaldehyde, eugenol, and thymol.

Preferred Embodiments

The following examples of preferred embodiments are provided for further understanding of the present compositions.

In one preferred embodiment, hereinafter referred to as F1, the composition consists of not more than 5% and not less than 0.5% β-pinene, not more than 5% and not less than 1% borneol, not more than 30% and not less than 10% cinnamaldehyde, not more than 5% and not less than 1% citral, not more than 5% and not less than 1% d-limonene, not more than 5% and not less than 1% eucalyptol, not more than 7% and not less than 1% eugenol, not more than 25% and not less than 20% farnesol, not more than 50% and not less than 25% linalool, not more than 2% and not less than 0.5 % thymol and not more than 7% and not less than 2% vanillin.

In another embodiment, the composition, hereinafter referred to as F2, consists of not more than 3% and not less than 0.25% β-pinene, not more than 3% and not less than 0.25% borneol, not more than 25% and not less than 10% cinnamaldehyde, not more than 5% and not less than 0.25% citral, not more than 5% and not less than 0.25% d-limonene, not more than 8% and not less than 1% eucalyptol, not more than 15% and not less than 5% eugenol, not more than 30% and not less than 20% farnesol, not more than 50% and not less than 25% linalool, not more than 2% and not less than 0.5% thymol and not more than 10% and not less than 5% vanillin.

In yet another embodiment, the composition, hereinafter referred to as F3, consists of not more than 7% and not less than 3% β-pinene, not more than 5% and not less than 1% borneol, not more than 20% and not less than 5% cinnamaldehyde, not more than 5% and not less than 1% citral, not more than 5% and not less than 1% d-limonene, not more than 10% and not less than 5% eucalyptol, not more not more than 15% and not less than 10% eugenol, not more than 20% and not less than 10% farnesol, not more than 50% and not less than 30% linalool, not more than 7% and not less than 2% thymol and not more than 20% and not less than 5% vanillin.

Independent analyzes of the preferred embodiments F1, F2 and F3 give the following results:

MIC ₉₉ represents the observed minimum inhibitory concentration of the test sample in eliminating 99% of the pathogen.

In order to assist in understanding the principles of the invention, this invention has been explained in connection with various embodiments, it should be understood that various modifications thereof will be apparent to those skilled in the art upon reading the description of the invention. Characteristics of different embodiments described in this document samples can be combined in one sample. Therefore, it is to be understood that the invention described herein is intended to cover such modifications as fall within the scope of the appended claims.

Claims (102)

1. Composition for inhibiting infection of E. coli, methicillin-resistant Staphylococcus aureus (MRSA), influenza virus, rhinovirus or M. Tuberculosis, containing: 0.25-7% β-pinene, 0.25-25% borneol, 5-30% cinnamaldehyde, 0.25-25% citral, 0.25-5% d-limonene, 1-10% eucalyptol, 1-15% eugenol, 10-30% farnesol, 25-50% linalool, 0.5-7% thymol and 2-7% vanillin. 2. Composition according to claim 1, containing: 0.25-3% β-pinene, 0.25-25% borneol, 10-25% cinnamaldehyde, 0.25-5% citral, 0.25-5% d-limonene, 1-8% eucalyptol, 5-15% eugenol, 20-30% farnesol, 25-50% linalool, 0.5-7% thymol and 5-20% vanillin. 3. Composition according to claim 1, containing: 3-7% β-pinene, 1-5% borneol, 5-20% cinnamaldehyde, 1-5% citral, 1-5% d-limonene, 5-10% eucalyptol, 10-15% eugenol, 10-20% farnesol, 30-50% linalool, 2-7% thymol and 5-20% vanillin. 4. Composition according to claim 1, containing: 0.5-5% β-pinene, 1-5% borneol, 10-30% cinnamaldehyde, 1-5% citral, 1-5% d-limonene, 1-5% eucalyptol, 1-7% eugenol, 20-25% farnesol, 25-50% linalool, 0.5-2% thymol and 2-7% vanillin. 5. The composition according to claim 1, further comprising its inclusion in a composition selected from the group consisting of soaps, lotions, detergents, shampoos, perfumes, body sprays, fabric softeners and wipes impregnated with an antistatic softener. 6. The composition of claim. 1, where this composition is made in the form of a solution for application in the form of a spray or aerosol. 7. A composition according to claim 2, wherein the composition is formulated as a solution for application as a spray or aerosol. 8. The composition of claim. 3, where this composition is made in the form of a solution for application in the form of a spray or aerosol. 9. The composition of claim. 4, where this composition is made in the form of a solution for application in the form of a spray or aerosol. 10. Composition for inhibiting infection of E. coli, methicillin-resistant Staphylococcus aureus (MRSA), influenza virus, rhinovirus or M. Tuberculosis, containing: 1-3% β-pinene, 1-5% borneol, 15-25% cinnamaldehyde, 1-3% d-limonene, 5-10% eucalyptol, 5-15% eugenol, 25-50% linalool, 0.5-2% thymol and 5-10% vanillin. 11. The composition of claim. 10, where this composition is made in the form of a solution for application in the form of a spray or aerosol. 12. A method of inhibiting infection with E. coli, methicillin-resistant Staphylococcus aureus (MRSA), influenza virus, rhinovirus, or M. tuberculosis, comprising administering a therapeutically effective amount of a composition according to claim 1 to a patient in need thereof. 13. The method according to p. 12, where this composition contains: 0.25-3% β-pinene, 0.25-25% borneol, 10-25% cinnamaldehyde, 0.25-5% citral, 0.25-5% d-limonene, 1-8% eucalyptol, 5-15% eugenol, 20-30% farnesol, 25-50% linalool, 0.5-7% thymol and 5-20% vanillin. 14. The method according to p. 12, in which the composition contains: 3-7% β-pinene, 1-5% borneol, 5-20% cinnamaldehyde, 1-5% citral, 1-5% d-limonene, 5-10% eucalyptol, 10-15% eugenol, 10-20% farnesol, 30-50% linalool, 2-7% thymol and 5-20% vanillin. 15. The method according to p. 12, in which the composition contains: 0.5-5% β-pinene, 1-5% borneol, 10-30% cinnamaldehyde, 1-5% citral, 1-5% d-limonene, 1-5% eucalyptol, 1-7% eugenol, 20-25% farnesol, 25-50% linalool, 0.5-2% thymol and 2-7% vanillin. 16. A method of inhibiting infection with E. coli, methicillin-resistant Staphylococcus aureus (MRSA), influenza virus, rhinovirus, or M. tuberculosis, comprising administering a therapeutically effective amount of a composition according to claim 10 to a patient in need thereof.