WO2007068007A1

WO2007068007A1 - Use of a disinfectant for treating respiratory tract infections

Info

Publication number: WO2007068007A1
Application number: PCT/ZA2006/000142
Authority: WO
Inventors: Harm Benjamin Steyn
Original assignee: Harm Benjamin Steyn
Priority date: 2005-12-07
Filing date: 2006-12-01
Publication date: 2007-06-14
Also published as: ZA200804944B

Abstract

The invention provides method of administering a treatment to a patient infected with an infective agent, said method comprising forming inhalable particles of a disinfectant, inhaling the disinfectant particles to deposit the disinfectant on the infected surfaces of the respiratory tract, sinuses, and the lungs, and repeating the inhalation periodically until the level of infection has decreased. The invention further provides a single use container for use in the method and the use of a disinfectant in the preparation of a medicament.

Description

USE OF A DISINFECTANT FOR TREATING RESPIRATORY TRACT INFECTIONS

Field of the Invention The invention relates to the treatment of upper respiratory tract infections, sinusitis, and lung infections.

Background to the Invention The inventor is aware that with the advent of so called "super bugs" many patients admitted to hospital become infected with pathogens such as Pseudomonas and eventually die from these infections of the lungs and respiratory tract rather than recovering from the ailment for which they were admitted in the first place.

These pathogens are dubbed "super bugs" due to their extreme resistance to known antibiotics and even antibiotic combinations so that once a patients infection level rises above a certain level it is almost impossible to treat the infection and the patient dies.

It is also known that with low infection levels even some single drug treatments can be effective. In cases where higher infection levels occur, combination therapies may be required. In this specification, the term "super bug" and "super bugs" denotes the group of microorganisms which are antibiotic resistant, including but not limited to:

Pseudomonas aeruginosa The inventor has thus identified a long felt and critical need to lower the infection levels of infected patients to a level where single or combination drug therapy can be effective and the patient can be saved. Summary of the Invention

According to a first aspect of the invention, there is provided a method of administering a treatment to a patient infected with an infective agent, said method comprising:

- forming inhalable particles of a disinfectant;

inhaling the disinfectant particles to deposit the disinfectant on the infected surfaces of the respiratory tract, sinuses, and the lungs; and repeating the inhalation periodically until the level of infection has decreased.

The invention thus also provides a method of treatment of a patient infected with an infective agent.

The infective agent may be bacteria.

The infective agent may be one or more virus.

The infective agent may be an amoeba. The infective agent may be a fungus.

The disinfectant may be a surface disinfectant.

The bacteria may be a super bug, as defined. Additionally, infections by other bacteria may also be treated by the invention, for example but not limited to:

Streptococcus pneumoniae

Haemophilus influenzae

Maraxella catarrhalis

Klebsiella pneumoniae

The method may include co-administering an anti-biotic drug at a dosage level which is not effective alone in treating the infection.

The anti-biotic may include one or more substance selected from the group including fluoroquinolones, such as ciprofloxacin, aminoglucosides, such as amikacin, β-lactam's, such as aztreonam, and polymyxin's, such as colistin The anti-biotic may be ciprofloxacin. The anti-biotic may be a floxacin drug.

The decrease in the level of infection may be sufficient for a patient to be considered to be cured, however, the decrease may be to level at which antibiotics which were not effective at higher infection levels are effective.

The method may include the contemporaneous administration of an antihistamine, a bronchodilator, and/or a steroid to reduce irritation and/or inflammation of the respiratory tract, sinuses, and lungs by the disinfectant.

The forming of the inhalable particles may be by sonic means, atomization by pressurized gas urging a fluid through a nozzle, or mechanical. Typically, for a liquid disinfectant, the forming of the particles is carried out by a nebuliser such as that used by asthma sufferers to inhale bronchodilators. T/ZA2006/000142

The disinfectant may be an alcohol.

The alcohol may be ethyl alcohol (ethanol).

The ethyl alcohol (ethanol) may be a weak solution of ethyl alcohol (ethanol), typically below 50 mass% ethyl alcohol (ethanol).

The ethyl alcohol (ethanol) may be 30 mass% or less of the inhaled volume.

The ethyl alcohol (ethanol) may be less than 15 mass% of the inhaled volume.

The ethyl alcohol (ethanol) may be diluted with one or more diluent, selected from the group including but not limited to, water and saline solution.

The ethyl alcohol (ethanol) may be approximately 30 mass% of the disinfectant with the balance being predominantly saline solution.

The method may include inhaling the disinfectant several times during a 24 hour period.

The inhalation of the disinfectant may be irregularly distributed over the 24 hour period. The inhalation regime may include three inhalations, spaced hourly, at the beginning of the 24 hour period followed by 21 hours without inhalation thereof.

According to a second aspect of the invention there is provided a single use container of disinfectant for use in the administration method described above.

The single use container may be a sachet, a glass ampoule, or a plastic bottle. 6 000142

The single use container may contain the disinfectant and a diluent.

The single use container may include an antihistamine.

The single use container may include a steroid, such as a corticosteroid, for example, cortisone.

The single use container may include an anti-inflammatory substance.

The single use container may include an anti-biotic in a quantity insufficient to be effective against an infection on its own.

The anti-biotic may include one or more substance selected from the group including fluoroquinolones, aminoglucosides, such as amikacin, β-lactam's, such as aztreonam, and polymyxin's, such as colistin.

A dose of the anti-biotic may be co-packaged with the container and not be mixed with the contents of the container.

The anti-biotic may be ciprofloxacin.

The single use container may hold less than 25 ml, typically less than 15 ml, usually from 1 ml to 10 ml.

A typical single use container contains 2.5 ml of a 10 mass% ethyl alcohol (ethanol) in saline solution.

Another typical single use container contains 10 ml of a 30 mass% ethyl alcohol (ethanol) in saline solution. ZA2006/000142

According to a third aspect of the invention there is provided the use of a disinfectant in the preparation of an inhalable medicament for the treatment of upper respiratory tract, sinusitis, and lung infections. The infections may be caused by one or more agents selected from bacteria, viruses, amoeba, and fungi.

The invention extends to a medicament comprising essentially of a disinfectant and saline solution for the treatment of upper respiratory tract, sinusitis, and lung infections.

The infections may be caused by one or more agents selected from bacteria, viruses, amoeba, and fungi. The disinfectant of the medicament may be ethyl alcohol (ethanol). The medicament may include an antihistamine.

The medicament may include a steroid, such as a corticosteroid, for example, cortisone.

The medicament may include an anti-inflammatory substance.

The medicament may include a bronchodilator.

The medicament may include an anti-biotic in a quantity insufficient to be effective against an infection on its own.

The anti-biotic may include one or more substance selected from the group including aminoglucosides, such as amikacin, β-lactam's, such as aztreonam, and polymyxin's, such as colistin The anti-biotic may be ciprofloxacin.

The invention extends to a method of prophylaxis for upper respiratory tract infections and lung infections, said method comprising:

forming inhalable particles of a disinfectant;

inhaling the disinfectant particles to deposit the disinfectant on surfaces of the respiratory tract, sinuses, and/or the lungs; and repeating the inhalation periodically thereby inhibiting infection thereof.

The infection may be caused by one or more agents selected from bacteria, viruses, amoeba, and fungi.

The bacteria may be a super bug, as defined.

Additionally, infections by other bacteria may also be treated by the invention, for example but not limited to:

Streptococcus pneumoniae

Haemophilus influenzae

Maraxella catarrhalis

Klebsiella pneumoniae

The method may include the contemporaneous administration of an antihistamine, a bronchodilator, and/or a steroid to reduce irritation and/or inflammation of the respiratory tract, sinuses, and lungs by the surface disinfectant.

The forming of the inhalable particles may be by sonic means, atomization by pressurized gas urging a fluid through a nozzle, or mechanical. Typically, for a liquid disinfectant, the forming of the particles is carried out by a nebuliser such as that used by asthma sufferers to inhale bronchodilators.

The disinfectant may be an alcohol.

The alcohol may be ethyl alcohol (ethanol).

The ethyl alcohol (ethanol) may be less than 35 mass% of the inhaled volume.

The ethyl alcohol (ethanol) may be about 30 mass% of the inhaled volume. The ethyl alcohol (ethanol) may be diluted with one or more diluent, including but not limited to, water and saline solution.

The method may include inhaling the surface disinfectant several times during a 24 hour period.

The inhalation of the surface disinfectant may be irregularly distributed over the 24 hour period.

The inhalation regime may include three inhalations, spaced hourly, at the beginning of the 24 hour period followed by 21 hours without inhalation thereof.

Description of an Example of Performing the Invention

The invention will now be described, by way of non-limiting examples only.

Example 1 A patient, Mr. S age 69, was diagnosed with chronic bronchitis and emphysema complicated by recurrent lower airway infections and colonization of airways with Pseudomonas aeruginosa and Streptococcus pneumoniae and was recurrently admitted to hospital into intensive care where combination antibiotic therapy was administered 19 times over a period of 36 months and the prognosis was bad.

The patient put himself onto a treatment method using as inhalable medicament a liquid surface disinfectant, ethyl alcohol (ethanol).

The method of treatment was followed for a period of two months and was monitored regularly by pathologists Lancet Laboratories of Pretoria, South Africa.

After a period of 2 months the Pseudomonas aeruginosa in a culture of sputum was reduced from "high growth" to "minimal growth" and whereas it was immune to antibiotic treatment when the inhalation therapy began it was treatable by a number of antibiotics, including aminoglucosides such as amikacin, and other antibiotics such as β-lactam's such as aztreonam, and polymyxin's such as

Colistin.

The sputum changed from purulent at the beginning of the inhalation treatment to clear at the end thereof.

The patient reported to be feeling much better and was mobile to the extent that he could resume most of his normal activities including running a business.

The inhalation treatment comprised inhalation from a nebuliser of an ethyl alcohol (ethanol) and saline solution three times within a 24 hour cycle, typically in the morning, afternoon and evening.

The alcohol and saline solution contained approximately 10 mass% alcohol. The inhalation was accompanied by a dose of Salbutimol (Venteze™) or Atrovent™. Each dose was approximately 20 ml of the alcohol and saline solution which amount was introduced into a nebuliser and inhaled.

Example 2 A patient diagnosed with chronic bronchitis and a sputum analysis was performed.

The pathologists reported that a culture of the sputum of the patient had a moderate growth of Pseudomonas aeruginosa.

The Pseudomonas aeruginosa was shown to be resistant to Ciprofloxacin.

For a period of 7 days the patient ciprofloxacin was administered orally to the patient at a rate of 500mg twice daily even though the pathologist report indicated this would not be effective.

Together with the course of ciprofloxacin the patient administered an inhalation from a nebuliser of an ethyl alcohol (ethanol) and saline solution three times daily. Each administration was carried out by nebulising 20 ml of a 30% m/m ethyl alcohol (ethanol) solution in saline solution with steam.

The patient also used a bronchodilator between administrations of the ethyl alcohol (ethanol) solution. After 14 days the patient was again examined and a sputum sample was sent to the same pathologist for analysis. The analysis showed that there was no trace of Pseudomonas aeruginosa in a culture of the sputum and that only normal respiratory flora were present. This result was unexpected as the Pseudomonas aeruginosa was shown to be resistant to ciprofloxacin and thus it was the co-administratioή of the inhalant that had the symbiotic effect of clearing up the infection.

Technical Evaluation of Examples of the Invention

Technical discussion

The effect of the treatment was evaluated by means of four main criteria: - Criteria 1 : Determination of the effect of the treatment on a number of known bacteria on an in vivo basis.

- Criteria 2: Determination of the effect of the solution on the viscosity of sputum.

- Criteria 3: Determination of the influence of the treatment on patients in terms of the absorption of the solution in the blood.

- Criteria 4: Determination of the effect of the treatment in prevention,

controlling or elimination of infections in the human body. This might be by means of combination therapy with known antibiotics, or as a separate treatment.

CRITERIA 1

The effect of the treatment on a number of known bacteria was tested in vivo by an independent laboratory, the South African Bureau of Standards (SABS), Pretoria, South Africa. In these tests the following bacteria were tested, for the purpose of illustrating the effectiveness of the treatment in eliminating some of the most aggressive bacteria. The bacteria tested is not considered to be a complete set of all the possible bacteria that might be treated, but merely serve as illustration of the more aggressive and life-threatening bacteria's reaction to the treatment. The following bacteria were tested by the SABS:

- Pseudomonas aeruginosa SATCC Pse 16

- Staphylococcus aureus SATCC Sta 59

- Klebsiella pneumoniae ATCC 10031 KIe 2 The dilution of the samples (ethyl alcohol (ethanol) with saline) was tested at 1/5 dilution. The samples were tested according to the method described in SANS 1615-1995 with approximately 10⁵ organisms per 10ml of test solution.

In the evaluation by the SABS, it was found that the treatment was extremely effective with the following test results, based on a single treatment with a 10 minute contact time:

Table 1: Effectiveness against bacteria

Between 46% and 57% of the bacteria were killed with a single treatment, which indicates very positive results. CRITERIA 2

A common problem which leads to increased infections, deterioration of quality of life, and higher susceptibility to secondary infections, is the fact that secretions from the upper respiratory tract and lungs are generally difficult to cough up. This is the result of decreased lung functions in some patients, and also primarily because of the nature of the secretions. The secretions are generally purulent and needs to be "broken up" to enable easier excretion thereof from the upper respiratory tract and lungs. The solution developed by the inventor has been proven to be very effective in achieving this, with sputum generally changing in substance from purulent at the beginning of the treatment to clear at the end there-of. CRITERIA 3

The solution may be made up of a dilution of ethyl alcohol (ethanol) and saline, or other elements. The question has arisen whether this will be safe to the human body.

The ingredients of the solution are generally consumed by people throughout the world, as alcohol consumption in reasonable quantities is very common, without any serious side effects. The quantities of the dosage is very low. For example, should a 20% ethyl alcohol (ethanol) dosage be used in a total of a 10 ml container (which might be a typical dosage), the alcohol content would be 2ml (20% x 10 ml). This can be compared to a beer of 340 ml, with 5% alcohol, resulting in 17 ml of alcohol. It can be seen that a standard beer would contain 8,5 times as much alcohol as what might be administered to a patient by means of the invention. Clearly, the dosage is within acceptable range to ensure that there are no negative side effects to the human body.

Furthermore, blood alcohol tests were conducted before and after the administration of the solution. The treatment consisted of inhalation of the solution by means of an ultrasonic nebuliser over a 10 minute time period. This was evaluated on 4 patients, with the following results.

Table 2: Blood alcohol tests

The test results, were reported by an independent laboratory, Ampath

Pathologists, Pretoria, South Africa.

CRITERIA 4

As set out in Examples 1 and 2, the solution proved to very effective in the treatment and control, both re-active and preventative based on the reaction of a patient, Mr. S. The patient, Mr. S age 69, was diagnosed with chronic bronchitis and emphysema complicated by recurrent lower airway infections and colonization of airways with Pseudomonas aeruginosa. Mr. S was recurrently admitted to hospital into intensive care where combination antibiotic therapy was administered 19 times over a period of 36 months and the prognosis was bad.

The patient put himself onto a treatment method using as inhalable medicament a liquid surface disinfectant, ethyl alcohol (ethanol), which was diluted with a saline solution. The method of treatment was followed for a period of 14 months. Since the treatment began, the patient was admitted to hospital only twice over the 14 month time period, which is significantly less than what was previously experienced. Preventative treatment: The patient responded very well in terms of the prevention of infections with bacteria, other than the super-bug, Pseudomonas aeruginosa. This is evident from the fact that only two infections was recorded from bacteria other than the super-bug. In March and July 2006 Moraxella catarrhalis infections was experienced, once at minimal growth level and once at profuse growth level.

These infections were extremely limited, given the history of the patient, being very susceptible to lung infections.

Combination treatment with known antibiotics: As set out in example 2 above, the patient responded very well in terms of the control of infections with bacteria, by administering the disinfectant inhaler in combination with known antibiotics. 00142

Normally Pseudomonas aeruginosa infections would only be controlled by means of intravenous antibiotics in a patient with the history of previous infections as is the case with Mr S. However, the combination treatment of the invention with the known oral antibiotics was effective in eliminating the super bug.

The inventor believes that the invention can contribute significantly to improve living conditions.

Recently there have been reports in the press about Klebsiella pneumoniae infections occurring in a number of babies in a South African hospital. These infections could potentially have been controlled by means of the treatment developed in this invention. This is only one example of numerous applications of the treatment to improve conditions of patients.

The inventor believes that although more research needs to be carried out on the efficacy against specific organisms the method of treatment and the medicament show great potential and already exhibit advantages over conventional therapies.

Claims

1. A method of administering a treatment to a patient infected with an infective agent, said method comprising:

- forming inhalable particles of a disinfectant;

2. A method as claimed in claim 1 , wherein the infective agent is bacteria.

3. A method as claimed in claim 1 or claim 2, wherein the disinfectant is a surface disinfectant.

4. A method as claimed in claim 2 or claim 3, wherein the bacteria is selected from the group including Pseudomonas aeruginosa, Streptococcus pneumonia, Haemophilus influenza, Maraxella catarrhalis, and Klebsiella pneumoniae.

5. A method as claimed in any one of the preceding claims, wherein the method includes co-administering an anti-biotic drug at a dosage level which is not effective alone in treating the infection.

6. A method as claimed in claim 5, wherein the anti-biotic is selected from fluoroquinolones, aminoglucosides, β-lactam's, and polymyxin's.

7. A method as claimed in claim 6, wherein the anti-biotic is ciprofloxacin.

8. A method as claimed in any one of the preceding claims, said method including contemporaneous administration of an antihistamine, a bronchodilator, and/or a steroid to reduce irritation and/or inflammation of the respiratory tract, sinuses, and lungs.

9. A method as claimed in any one of the preceding claims, wherein the inhalable particles are formed by sonic means, atomization by pressurized gas urging a fluid through a nozzle, or mechanical means.

10. A method as claimed in any one of the preceding claims, wherein the disinfectant is an alcohol.

11. A method as claimed in claim 10, wherein the alcohol is ethyl alcohol (ethanol).

12. A method as claimed in claim 11, wherein the ethyl alcohol (ethanol) in the method is a weak solution of ethyl alcohol (ethanol), typically below 50 mass% ethyl alcohol (ethanol).

13. A method as claimed in claim 12, wherein the ethyl alcohol (ethanol) is 30 mass% of the inhaled volume.

14. A method as claimed as in any one of claims 11 to 13, wherein the ethyl alcohol (ethanol) is diluted with one or more diluent, selected from the group including but not limited to, water and saline solution.

15. A method as claimed in any one of the preceding claims, which includes inhaling the disinfectant several times during a 24 hour period.

16. A method as claimed in claim 15, wherein the inhalation of the disinfectant is performed three times in a 24 hour period.

17. A single use container of disinfectant for use in the administration method as claimed in any one of the preceding claims.

18. A single use container as claimed in claim 17, which container is selected from a sachet, a glass ampoule, or a plastic bottle.

19. A single use container as claimed in claim 17 or claim 18, containing the disinfectant and a diluent.

20. A single use container as claimed in any one of claims 17 to 19, including one or more of an antihistamine, a steroid, an anti-inflammatory substance, and an anti-biotic in a quantity insufficient to be effective against an infection on its own.

21. A single use container as claimed in claim 20, wherein the anti-biotic includes one or more substance selected from the group including fluoroquinolones, aminoglucosides, β-lactam's, and polymyxin's.

22.A single use container as claimed in any one of claims 20 or 21, wherein a dose of the anti-biotic is co-packaged with the container and is not mixed with the contents of the container.

23.A single use container as claimed in any one of claims 17 to 22, wherein the single use container holds less than 25 ml.

24.A single use container as claimed in any one of claims 17 to 23, which container contains 20 ml of a 30 mass% ethyl-alcohol in saline solution.

25. Use of a disinfectant in the preparation of an inhalable medicament for the treatment of upper respiratory tract, sinusitis, and lung infections.

26. Use as claimed in claim 25, wherein the medicament comprises of disinfectant and saline solution for the treatment of upper respiratory tract, sinusitis, and/or lung infections.

27. Use as claimed in claim 25 or claim 26, wherein the infections are caused by one or more agents selected from bacteria, viruses, amoeba, and fungi.

28. Use as claimed in any one of claims 25 to 27, wherein the disinfectant of the medicament is ethyl alcohol (ethanol).

29. Use as claimed in any one of claims 25 to 28, which medicament includes one or more of an antihistamine, a steroid, an anti-inflammatory substance, a bronchodilator, and an anti-biotic in a quantity insufficient to be effective against an infection on its own.

30. Use as claimed in claim 29, wherein the anti-biotic includes one or more substance selected from the group including fluoroquinolones, aminoglucosides, β-lactam's, and polymyxin's.

31. Use as claimed in any one of claims 29 or 30, wherein a dose of the antibiotic is co-packaged with the container and is not mixed with the contents of the container.

32. Use as claimed in any one of claims 25 to 31 , wherein the disinfectant is less than 50 mass% of the medicament.

33. Use as claimed in claim 32, wherein the disinfectant is 20 mass% of the medicament.

34. Use as claimed in any one of claims 25 to 33, wherein the medicament includes saline solution.