IT202000023269A1 - COMPOSITION FOR THE TREATMENT OF SYMPTOMS ASSOCIATED WITH DISEASES OF THE RESPIRATORY TRACT - Google Patents

Description

Description of the patent for an industrial invention entitled:

?COMPOSITION FOR THE TREATMENT OF SYMPTOMS ASSOCIATED WITH DISEASES OF THE RESPIRATORY TRACT?

The present invention relates to a composition for the treatment of symptoms associated with respiratory tract pathologies.

Technical background

At the end of 2019, a new serious respiratory disease (coronavirus disease 2019, COVID-19) ? emerged in Wuhan, China and since then ? became pandemic in a few months, with approx. 11 million people infected worldwide to date. COVID-19 ? caused by a new coronavirus called (SARS) CoV-2 to distinguish it from the virus called SARS-CoV that emerged in Guangdong province in China in 2003 and caused the serious medical condition known as SARS. Like SARS-CoV, SARS-CoV-2 causes severe pneumonia that can lead to acute respiratory distress syndrome (ARDS) and death. However, unlike SARSCoV, SARS-CoV-2 can cause multi-organ disease and hypercoagulation on the one hand and mild symptoms limited to upper respiratory tract infection on the other. High viral loads were detected in nasal swabs even in the presence of mild symptoms or in asymptomatic subjects.

The main route of transmission of SARS-CoV-2 ? through mucous contact with infected exhaled droplets. Considering the higher viral load detected in the nose, compared to the lower respiratory tract, this may be one of the first anatomical structures exposed to viral contagion as evidenced by the fact that acute anosmia ? a relatively common symptom. With the rapid spread of COVID-19, healthcare systems have faced the challenge of treating huge numbers of patients for whom there is no immunity. widespread. There is currently no specific treatment. Many off-label therapies have been tried but so far with uncertain results.

Those who contract the infection are isolated and treated, mostly at home, with supportive therapies aimed at monitoring symptoms.

Acetic acid, the active component of vinegar, is a well-known disinfectant agent. Inhaling an aqueous solution of acetic acid to treat symptoms of the common cold is a well-known folk remedy in Italy.

The activities antibacterial and antiviral properties of acetic acid are documented in the literature. Acetic acid causes the inactivation and breakdown of hemagglutinin glycoproteins (present on the surface of influenza viruses) generating a conformational change of those glycoproteins, destroying the viral envelope and inhibiting viral transmission.

In order to mitigate virus replication and its effects on the upper respiratory tract mucosa, including acute anosmia (a frequent early symptom of SARS-CoV-2 infection), fumigation of vinegar diluted in boiling water to a concentration of 0.34% for 15 minutes ? been adopted as an empirical practice in COVID-19 patients, in whom ? improvement of symptoms such as cough and fever was found in > 90% of individuals (Pianta L et al. Acid Acetic disinfection as a potential adjunctive therapy for non-severe COVID-19. European Archives of Oto-RhinoLaryngology 2020).

DESCRIPTION OF THE INVENTION

Yup ? it has now been found that the association of vinegar (or an equivalent aqueous solution of acetic acid) with essential balsamic oils and any other components such as film-forming and mucolytic agents, when administered by inhalation, in particular by fumigation, significantly improves the activity? of vinegar and allows effective treatment of corona virus infections, in particular of Covid-19.

The invention therefore relates to inhalation compositions comprising vinegar or an aqueous solution of acetic acid with a concentration of from 3 to 10% by weight and at least one essential oil having an active activity. balsamic.

AND? preferred, for its wide availability? and low cost, the vinegar typically having an acetic acid content of about 5-6% by weight.

The balsamic essential oils are preferably selected from eucalyptus oil, mountain pine oil, thyme oil and mint oil.

White thyme oil has a fluidifying action on bronchial secretions and contributes to the well-being of the nose and throat; eucalyptus oil promotes functionality? of the mucous membranes of the respiratory system and the well-being of the throat with a balsamic, soothing and emollient action while the essential oils of mint and pine have a balsamic effect.

The compositions of the invention preferably also comprise a film-forming agent.

Examples of suitable film-forming agents include polyvinylpyrrolidone, ethylcellulose, methylcellulose, hydroxypropylmethylcellulose, polyethylene glycol, hyaluronic acid, native or hydrolysed collagen, polysaccharides extracted from nopal, prickly pear, plantain, mallow, marshmallow or tamarind, xyloglucans, pullulans, fucoidans, ulvans, mucin, glucomannan arabinogalactan, guar gum, agar, pectin.

Known mucolytics that can be administered by inhalation, such as N-acetylcysteine and methylsulfonylmethane (MSM), preservative and solubilizing agents, may also be present.

The percentage by weight of vinegar can? vary from 90 to 98% while each essential oil? present in weight percentages between 0.001 and 0.1%. Are preferably included two or more? preferably three or four essential oils selected from those indicated above.

The percentage by weight of filming agent can? range from 0.0001 to 0.01%.

The hypothesized mechanism of action is based, in addition to the properties? of vinegar as described above, also on the barrier effect which limits contact with pathogens by protecting the mucous membranes. Such an effect? synergistic with the antibacterial and balsamic essential oils.

The compositions of the invention act both on the mucous membranes of the respiratory tract (nose, oral cavity, lungs), limiting contact with pathogens thanks to a "barrier effect", and on the fluidisation of the mucus, performing a balsamic and emollient action . Considering the ease of treatment, the economic aspects and the absence of side effects, the compositions of the invention offer the possibility of an additional treatment particularly suitable for the less severe forms of Covid-19 as well as for other respiratory system infections such as colds and flu.

The compositions of the invention can be administered in any form suitable for the inhalation route, for example by aerosol. Preferred form of administration? that in fumigation: the inhalation of water vapor generated by fumigation allows in fact the formation of a suspension of very small particles that allow the dissolved ingredients to access the respiratory mucous membranes easily. and effectiveness. The optimal temperature for fumigation? between 37?C and 45?C. A possible way? administration involves the dilution in hot or boiling water (for example about 500 ml) of 10-50 ml of the composition and the inhalation of the vapors for about 10 minutes two or more? times a day.

The following examples illustrate the invention in greater detail.

Example 1- Quantitative composition

Example 2 - In vitro tests: inhibition of SARS-CoV-2 replication

For purpose? of research ? Has the exact concentration used for fumigation in patients infected with SARS-CoV-2 been replicated, and is it? a correlation curve was then made between the concentration of vinegar (diluted from 0.28% to 0.008% in PBS) and the viral inhibition response by the vinegar on an experimental model based on plaque formation (PFU) put developed and optimized in the case of Zika virus on African monkey epithelial cells, correlating the concentration of plaque inhibition resulting from treatment with the virus after treatment.

Diluted vinegar effectively inhibited SARS-CoV-2 plaque formation by 80% at a concentration of 0.28% with an inhibitory effective concentration 50 (IC50) of 0.08% (Figure 1A); to notice ? the fact that this vinegar dilution was not toxic to the cells (Figure 1B) as revealed by the activity levels? of adenylate kinase (AK Activity) released in culture supernatants as an indicator of plasma membrane damage and cell necrosis. because the active component of vinegar ? the? acetic acid, yes ? subsequently evaluated its activity? anti-SARS-CoV-2.

Incubation of SARS-CoV-2 with 0.5% acetic acid in PBS for 15 minutes at 37°C reduced SARS-CoV-2 plaque formation by 89% with an IC50 of 0.14% (Figure 1C) without evidence of cytotoxicity? (Figure 1D).

Yup ? moreover, the inhibition effect of viral replication was studied as a function of the temperature of the administration, an important parameter in view of the administration by fumigation at 45°C for 15 min. ? A significant decrease in plaque formation was observed by infecting cells with virus and treated at 45°C with 0.28% vinegar diluted in PBS compared with untreated controls at 37°C (Figure 2).

Also, when is the vinegar solution ? been heated to 45?C for 15 minutes, ? an additional significant reduction to 90% was observed compared to the viral inoculum treated at 37°C.

Subsequently ? Was it evaluated whether vinegar could inactivate infectiousness? of SARS-CoV-2 present in a nasopharyngeal swab transport medium. To this end, the medium of the swab ? was tested directly in a plaque assay in the presence of diluted vinegar at a concentration of 0.14%.

When the medium (50 or 10 ?l) ? been added to the cells of Verum, yes ? recorded the formation of plaques proportional to the volume of the medium and ? It was observed that vinegar significantly reduced the number of plaques. When tested at 45?C, viral plaques generated by 10?l of transport medium were reduced to almost zero.

because the number of plaque was 5 times lower with 10 µl of medium than with 50 µl, the results were pooled as shown in Figure 3. The mean number of plaques in the control sample was 248 µl. 18 at 37?C while at 45?C ? significantly decreased (about 50%) the number of plaques. The vinegar reduced the plaque yield to approx. 50% at 37?C and up to 90% at 45?C.

Claims (8)

1. Inhalation compositions comprising vinegar or an aqueous solution of acetic acid with a concentration of from 3 to 10% by weight and at least one essential oil with active balsamic. 2. Compositions according to claim 1 comprising vinegar with acetic acid titre of 6% by weight. 3. Compositions according to claim 1 or 2 wherein the balsamic essential oils are selected from eucalyptus oil, mountain pine oil, thyme oil and mint oil. 4. Compositions according to one or more? of claims 1 to 3 comprising a film-forming agent. 5. Compositions according to claim 4 in which the film-forming agent is selected from polyvinylpyrrolidone, ethylcellulose, methylcellulose, hydroxypropylmethyl cellulose, polyethylene glycol, hyaluronic acid, native or hydrolysed collagen, polysaccharides extracted from nopal, prickly pear, plantain, mallow, marshmallow or tamarind, xyloglucans, pullulans, fucoidans, ulvans, mucin, arabinogalactan , glucomannan, guar gum, agar, pectin. 6. Compositions according to one or more? of claims from 1 to 5 administrable as fumigation. 7. Compositions of claims 1-6 for the treatment of coronavirus, influenza virus, rhinovirus infections. 8. Compositions for use according to claim 7 for the treatment of Covid-19, cold and flu.