CH703437A2 - Use of an active mixture of essential oils and volatile synthetic molecules as pulmonary tuberculosis therapy by inhalation of the mixture which is essence of clove, eugenol, thyme, synthetic thymol and methyl jasmonate - Google Patents

Abstract

Use of an active mixture of essential oils and volatile synthetic molecules as pulmonary tuberculosis therapy by inhalation of the mixture which is constituted of essence of clove, eugenol, thyme, synthetic thymol and methyl jasmonate ( Hedione(RTM: Methyl dihydrojasmonate) in different combinations, is claimed. ACTIVITY : Antitubercular; Tuberculostatic. MECHANISM OF ACTION : None given.

Description

Introduction and current state of science

Tuberculosis is a contagious disease affecting mainly the lung, but can also affect other parts of the body, such as the spine, brain and kidneys. The pathogen, Mycobacterium tuberculosis, is transmitted by droplets of cough and sputum.

[0002] Tuberculosis is affecting more and more people, especially in developing countries where there is a large number of HIV / AIDS patients with poor access to health care.

[0003] Mycobacterium tuberculosis has a lipid envelope and is developing more and more resistance to the chemical agents of the usual treatments and its eradication is long. A considerable improvement in the treatment of tuberculosis by a mixture of essential oils which is breathed by the patient is the subject of the patent application described below.

The Invention

We found that the mixture of three volatile products having a synergistic action and is able to kill Mycobacterium tuberculosis when it is in contact with the vapors of this mixture.

This mixture consists of these three substances: <tb> 1. <sep> Essential oil of clove obtained by stillation of the leaves or buds (cloves) of the Eugenio Caryophyllata tree. <tb> 2. <sep> Essential oil of red thyme obtained by distillation of the whole plant Thymus Vulgaris. <tb> 3. <sep> Methyl Jasmonate, a molecule found naturally in green tea.

The active substance in clove oil is eugenol which can be isolated by distillation of crude clove oil. The active substance in the essence of thyme is thymol which is also accessible by chemical synthesis. Methyl Jasmonate is present in green tea, but for perfumes and flavors only the chemical synthesis molecule known commercially under the name "Hedione" from Firmenich in Geneva, Switzerland, is used.

Theoretically we could use these pure substances but we found that their action in the whole of the natural essential oil that contains in addition a multitude of other active molecules is significantly superior and more enjoyable to use. In addition to the bactericidal action of the active mixtures mentioned, it is possible to add essential oils or molecules having an anti-inflammatory action.

[0008] Mycobacterium tuberculosis causes by its action which includes among others the lipoxygenase enzyme an inflammation of the surrounding tissue. As a result, volatile substances having an antioxidant action (free radical scavengers and peroxides) which decrease inflammation have a beneficial effect when they are inhaled together with the active mixture. The essence of sage, bergamot, lemon, vetiver, chamomile, vanillin and others has an anti-inflammatory effect.

Example 1

Active mixture No 1: <tb> Rectified clove oil <sep> 50.0% <tb> Essence of thyme <sep> 20.0 <Tb> Hedione <September> 30.0

This mixture is tested according to the growth inhibition method. Test germ: Mycobacterium tuberculosis ATCC 25177

Culture medium: Löwenstein-Jensen agar (see Murray et al., Manual of Clinical Microbiology, 7. Ed ASM press). The culture agar is in a test tube with the sloping surface. Mycobacteria are inoculated on the surface of the agar. Then 100 microliters of the active mixture was poured onto the inoculated surface. The specimens are then incubated at 37 ° C for a period of 6 weeks. After the growth of Mycobacterium was compared with a control that had not received the active mixture. We observed complete growth inhibition on the surface directly affected by the active mixture 1 and greatly reduced growth on the surface affected only by the vapors of this mixture.

Example 2

Using the same test seeds inoculated on the same culture medium as described in Example 1 we sprayed the following mixture on the culture surface Previously inoculated:

Active mixture 2: <tb> Rectified clove oil <sep> 40.0% <tb> Essence of thyme <sep> 20.0 <tb> Synthetic Thymol <sep> 10.0 <Tb> Hedione <September> 30.0

The vaporization was carried out with a device Aeroneb ProX-fogger (manufacturer Aerogen Ltd., Galway, Ireland)

For the practical test, a culture growth of Mycobacterium tuberculosis of one week was exposed for 5 minutes to microdroplets and vapors of the active mixture. To obtain a better vaporization, each active mixture was diluted as follows: 20% active mixture in ethanol 30% sol. aqueous. Active mixture 1 and 2 were tested in parallel. Then the specimens are incubated at 37 ° C for 24 hours. This procedure is repeated for 10 consecutive days.

At the end of this period the growth of bacteria was greatly reduced in visual comparison with the untreated control.

It is known that ethanol alone has no action on Mycobacterium tuberculosis. As a result, the inhibitory action is due only to the active mixtures.

Example 3

The same test described in Example 2 was repeated using an aerosol spray with liquefied propellant instead of the nebulizer.

Aerosol formula: <tb> 2.0% <sep> active mixture 1 or 2 <tb> 98.0% <sep> propane / butane propellant 2.5 bar

Application:

4 times 1 second of spray were directed to the agar surface previously inoculated with Mycobacterium tuberculosis and incubated for 1 week at 37 ° C. After the test specimen is incubated again at 37 ° C. Each day this same treatment is applied to the agar surface for a period of 7 days.

Result:

We observed a complete growth inhibition of Mycobacterium tuberculosis after 7 days of treatment already. Active mix 1 and 2 showed the same results. To verify the lethal effect of these formulas we subcultivated Mycobacteria from the treated agar surface on the same fresh Löwenstein-Jensen culture medium and incubated for 6 weeks at 37 ° C to check for presence of living cells. No growth was observed on the treated specimens. On the other hand, the subculture of the control without treatment showed a strong growth after 2 weeks of incubation already.

Claims (6)

1. Use of an active mixture of essential oils and volatile synthetic molecules as a therapy for pulmonary tuberculosis by inhalation of said mixture which consists of clove oil, eugenol, thyme oil, synthetic thymol and methyl Jasmonate (Hedione ) in different relationships. 2. Use of an active mixture of essential oils and volatile synthetic molecules according to claims 1 and 2, characterized in that this active mixture contains in addition other essential oils and molecules which have an anti-inflammatory action, especially sage, chamomile , bergamot, lemon and vanillin. 3. Use of a mixture of essential oils and volatile synthetic molecules according to claims 1 and 2, characterized in that this mixture is premixed with ethanol and water in varying concentrations and then sucked into the lungs using a pharmaceutical ultrasonic nebulizer. 4. Use of a mixture of essential oils and volatile synthetic molecules according to claims 1,2 and 3, characterized in that this mixture is sucked into the lungs using an aerosol spray. 5. Use of a mixture of essential oils and volatile synthetic molecules according to claims 1, 2, 3 and 4, characterized in that this mixture is sucked into the lungs using a compressed air venturi system. 6. Use of a mixture of essential oils and volatile synthetic molecules according to claims 1, 2, 3, 4 and 5, characterized in that this mixture is sucked into the lungs using a vapor distillation system water by heating the said active mixtures with water and breathing the mixture of these vapors.