Ethene containing solutions and use thereof in methods of...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Hydrocarbon doai

Reexamination Certificate

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Reexamination Certificate

active

06384086

ABSTRACT:

TECHNICAL FIELD
This invention relates generally to ethene containing solutions and to the use thereof in methods of therapy or prophylaxis.
BACKGROUND OF THE INVENTION
The current state of the art in respect of the metabolic role of ethene in mammals is best described in International Agency for Research on Cancer: Monographs of the Evaluation of Carcinogenic Risks to Humans Vol 60, 1994, Ethylene, as published by the World Health Organization. From this reference it may be concluded that ethene has no useful metabolic role in mammals (apart from use as an anaesthetic) and that its production or uptake by mammals seems to be without useful metabolic purpose.
The state of the art was advanced in specification PCT/NZ94/00151 (published as WO 95/17214 and for which the present applicant is an inventor) by the suggestion that ethene production by mammals may be a defense mechanism directed against invading micro-organisms. The use of ethene as a novel sterilizing agent was therefore described therein. Particularly described were sterilizing or micro-organism inhibiting solutions comprising ethene solubilized in a suitable liquid.
It was indicated that the solutions of WO 95/17214, would have utility in prophylaxis and/or therapy through a direct antimicrobial effect on infective or disease causing agents.
The application has now identified a disadvantage associated with the use of the solutions of WO 95/17214. These solutions have been found to exhibit poor storage and chemical stability. This lack of stability is believed to result from ethene's ability to react with other components in solutions.
More specifically, the applicant has found that ethene may react with other components in a liquid resulting in one or more of, a reduction in the amount of ethene in solution, alteration in the pH of the solution or the production of undesirable reaction products. The applicant has surprisingly found that ethene in solution may be reduced by 50% for example by reaction with such components. The applicant has found such reactions entirely unanticipated and at variance with the disclosure of WO 95/17214.
These components may comprise ions, for example H+ and OH− ions, calcium ions, or other impurities such as microscopic plant matter, calcium solids, or entrained gases, for example, air, oxygen or chlorine.
While not bound by the following, it is suggested for example, that one reaction may be between hydroxy ions and ethene forming 2-hydroxy ethene. Similarly, oxygen entrained in an ethene containing solution may also react with ultra violet light, or even neon light to produce ozone which subsequently reacts with ethene to produce ethylene oxide. The presence of a carcinogen such as ethylene oxide greatly reduces the utility of the ethene containing liquid for consumption. Moreover, all of these reactions may reduce the amount of ethene solubilized in the liquid.
By way of example, the applicant has found that ethene added to a suitable liquid, in this case water of a potable standard containing components giving a conductivity of 148 micromhos (reciprocal megohms) per centimetre, reacted to give a rise in pH which may continue over days and months of storage. A similar reaction was not observed when the water used was deionised by distillation to substantially zero conductivity prior to the addition of ethene.
A lack of storage stability is particularly disadvantageous for this ethene product if it is to be involved in lengthy transport operations, or where an extended shelf life is desirable.
As noted above, the applicant has now surprisingly found that an ethene containing solution exhibiting usefully increased chemical and storage stability can be produced by solubilizing ethene in a reactivity reduced liquid. The solution produced is useful as a tonic.
It is therefore an object of the invention to provide a storage stable solution comprising ethene solubilized in a suitable liquid or at least to provide the public with a useful choice.
It is a further object of the invention to provide methods of prophylaxis and/or therapy in which the storage stable solution is used as a directly active antimicrobial agent, or again at least to provide the public with a useful choice.
It was also the applicant's expectation that the solutions of WO 95/17214 would have utility in prophylaxis and/or therapy through a direct antimicrobial effect on infective or disease causing agents. However, the applicant has found that ethene containing solutions may not have a direct sterilizing/inhibiting effect against a number of micro-organisms in vitro. Some examples of micro-organisms found by the applicant not to be sterilized in vitro by solubilized ethene are: Influenza A (H3N2), Poliovirus type 1 (Sabin) and Herpes simplex virus. In addition to these viruses, eight bacterial strains representing four bacterial genera (Staphylococcus, Pseudomonas, Klebsiella, Enterococcus) of important human pathogens were tested in vitro without apparent sterilizing success.
The applicant has surprisingly found that, notwithstanding the apparent lack of an in vitro antimicrobial efficacy of ethene on certain micro-organisms, ethene, more particularly solubilized ethene, may provide prophylactic and/or therapeutic effects in vivo in hosts to which the ethene is administered. This is even against a micro-organism such as Herpes simplex which ethene does not inhibit or sterilize in vitro. In other words, an ethene induced micro-organism sterilizing/inhibiting effect may be observed in a host, even though the micro-organism(s) within that host may not be directly ethene labile. In this respect the applicant has found that a useful metabolic role of ethene in man is the same as its useful metabolic role in plants, that of a primary immunogen. It is upon this entirely unexpected finding that this invention is also partly based.
It is therefore a further object of the invention to provide methods of prophylaxis and/or therapy in which ethene is used otherwise than as a directly active antimicrobial agent, or at least to provide the public with a useful choice.
SUMMARY OF THE INVENTION
In a first aspect, the present invention can be said to broadly consist in a storage stable solution comprising ethene solubilized in a suitable liquid. The storage stable solution is preferably a tonic solution comprising ethene solubilized in a reactivity reduced liquid.
Desirably, the liquid is purified. Most preferably, the liquid is a deionized liquid.
In a general aspect, the present invention provides a method for improving metabolic function in a host which method involves administering to the host an effective amount of a storage stable solution of the invention.
In a further aspect, the present invention provides a method for prophylaxis and/or therapy for the treatment of diseases or infections in a host by exerting a direct antimicrobial effect, and which involves the step of administering to the host an effective amount of a storage stable solution of the invention.
In a related aspect, the present invention provides the use of a storage stable solution of the invention in the preparation of a medicament for use in prophylaxis and/or therapy against microbial infection, whereby the medicament exerts a direct antimicrobial effect.
In a still further aspect, the present invention can be said to broadly consist in a method for prophylaxis and/or therapy for the treatment of diseases or infections in a host other than through exerting a direct antimicrobial effect and which involves the step of administering to the host an effective amount of ethene.
More generally, the invention provides a method of improving metabolic function in a host which method involves the step of administering to the host an effective amount of ethene, and provided that the improved metabolic function is achieved other than through exerting a direct antimicrobial effect
In a further aspect, the present invention provides a method of priming and/or causing a host to mount a protective response, more particularly a protective immune respons

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