WO2008117091A2 - Treatments for bacterial, parasitic, fungal and prionic infections - Google Patents
Treatments for bacterial, parasitic, fungal and prionic infections Download PDFInfo
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- WO2008117091A2 WO2008117091A2 PCT/GB2008/050215 GB2008050215W WO2008117091A2 WO 2008117091 A2 WO2008117091 A2 WO 2008117091A2 GB 2008050215 W GB2008050215 W GB 2008050215W WO 2008117091 A2 WO2008117091 A2 WO 2008117091A2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/40—Peroxides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/16—Fluorine compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/18—Iodine; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01C—AMMONIA; CYANOGEN; COMPOUNDS THEREOF
- C01C3/00—Cyanogen; Compounds thereof
- C01C3/20—Thiocyanic acid; Salts thereof
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the present invention relates to a treatment, a method of preparing the same and a kit for preparing the same.
- Infection is caused by a foreign species colonizing in a host organism and utilizing the hosts resources in order to multiply. Infections can have severe detrimental effects in the host including inflammation of the infected area which can lead in some cases to severe trauma to the host and even death. Infections can be bacterial, parasitic, fungal or prionic. Common infections that may affect humans include: cholera, leprosy and bubonic plague, E. CoIi, Salmonella, MRSA and infections due to genetic immune deficiencies.
- anti-infection agents are used to treat infections by killing or preventing the growth of the foreign species without harming the host.
- Many different anti-infection agents have been developed and are effective against different foreign species, but can have a detrimental effect on the host.
- a treatment for an infection comprising the products formed from a peroxidase catalysed reaction between an oxidisable species and at least one oxygen donor, in aqueous solution; wherein the original peroxidase enzyme has been removed therefrom.
- the infection may be a bacterial infection (an infection caused by one or more bacterium) ; a parasitic infection (an infection caused by one or more parasite) ; a fungal infection (an infection caused by one or more fungus); and/or a prionic infection (an infection caused by one or more prion) .
- the treatment may be orally administrable, topically administrable, administrable as a wash or douche, or administrable by inhalation.
- the treatment may be orally administrable as an aqueous solution.
- the treatment may be administered topically or orally by any of a spray, a gel, a bath, a wetted cloth.
- the treatment may be administered by inhalation by spray, humidified air or fog.
- treatment refers to a pharmaceutical composition.
- the oxidisable species comprises any species operable to be oxidised by the oxygen donor in the presence of a peroxidase enzyme.
- the oxidisable species may comprise a source of thiocyanate ions.
- the source of thiocyanate ions may be any substance that provides free thiocyanate ions in aqueous solution, for example a metal salt thereof such as any of a sodium, potassium, lithium salt etc.
- the source of thiocyanate ions may be derived from hydrogen thiocyanate .
- the source of thiocyanate ions may be as reaction products of a further reaction.
- thiocyanate ions means [SCN] " ions.
- the oxidisable species may comprise a source of halide ions.
- the source of halide ions may be any substance that provides free halide ions in aqueous solution, for example a metal halide salt.
- the source of halide ions may comprise a source of one or more of fluoride ions, chloride ions, bromide ions or iodide ions.
- Suitable metal salts include any halide salt that readily dissociates in aqueous solution to provide the free halide ion.
- the salt may be a group I metal salt such as lithium, sodium, potassium etc .
- the treatment further comprises an amount of the oxidisable species.
- the treatment may comprises the products formed from a peroxidase catalysed reaction between an oxidisable species and at least one oxygen donor, in aqueous solution; and an amount of unreacted oxidisable species.
- the oxidisable species is present in the treatment in an amount (by mol) in excess of the said formed products.
- the ratio of the oxidisable species present in the treatment to the amount of the said formed products is at least about 1.1:1 (by mol), more preferably at least about 1.2:1 (by mol), more preferably at least about 1.3:1 (by mol), most preferably at least about 1.4:1.
- the ratio of the oxidisable species present in the treatment to the amount of the said formed products is about 1.5:1 (by mol) .
- the oxidisable species may be [SCN] " and the said formed products may comprise [OSCN] " .
- [SCN] " is present in the treatment in an amount (by mol) in excess of the [OSCN] " .
- the oxidisable species present in the treatment may be different to the oxidisable species from which the said formed products are derived.
- the oxidisable species from which the said products are formed may be [SCN] "
- the oxidisable species present in the treatment may be a source of halide ions, such as Cl " , for example.
- the source of the oxidisable species may be present in the reactants (prior to the peroxidase catalysed reaction) in a concentration such that the oxidisable species in the reactants is present in the aqueous solution at a concentration of about 0.1 to 5OmM. More preferably, about 0.5 to 1OmM, more preferably between about 1 and 5mM. In a most preferred embodiment, about 2mM.
- the at least one oxygen donor comprises a source of peroxide.
- the source of peroxide may be any entity that comprises the group X-O-O-Y, where 0 represents an oxygen radical.
- one of or both of X and Y may be hydrogen.
- the source of peroxide may be hydrogen peroxide.
- Either of X and/or Y may represent a chemical species, such as an organic fragment or, in one embodiment, may represent a surface to which the -0-0- group is bound. If X and/or Y represents a surface to which the -0-0- group is bound, then a linking group between the -0-0- group and the surface may be present, such as a bivalent organic bridging group, for example. Alternatively, X and/or Y may represent an inorganic species, such as magnesium, sodium etc.
- the source of peroxide may be present in the reactants
- a concentration such that the peroxide species in the reactants in aqueous solution is present at a concentration of about 0.1 to 5OmM. More preferably, about 0.5 to 1OmM, more preferably between about 1 and 5mM.
- the source of peroxide may be an organic peroxide compound or salt thereof.
- the peroxidase enzyme is a lactoperoxidase enzyme .
- the lactoperoxidase may be naturally occurring lactoperoxidase, for example as extracted from milk. Alternatively, the lactoperoxidase may be artificially synthesised.
- the peroxidase enzyme is provided on one or more support.
- the support is an inorganic clay material.
- the support may comprise bentonite .
- the peroxidase enzyme is present in the reactants (prior to the peroxidase catalysed reaction) in an amount of between about 0.001 to 10 g/1. More preferably, 0.005 to 5 g/1.
- the peroxidase enzyme is present in the treatment in an amount less than about 0.001 g/1. More preferably, the peroxidase enzyme is present in the treatment in an amount less than about 0.0005g/l. More preferably, the peroxidase enzyme is present in the treatment in an amount less than about O.OOOlg/1. More preferably, the peroxidase enzyme is present in the treatment in an amount less than about O.OOOOlg/1.
- the treatment comprises substantially no peroxidase enzyme therein.
- the reaction can occur over a range of pH depending on the desired use of the resulting active species.
- the reaction can occur between pH 3 and pH 11 (measured at 25 0 C) .
- the reaction takes place between pH 4 and pH 10 (measured at 25 0 C) .
- the reaction is performed in a temperature range between 2 0 C and 6O 0 C.
- a temperature may be chosen to correspond with the intended use. For example, at higher temperatures, the stability of the oxidised species is lower (and therefore degrades faster) than at lower temperatures.
- the reaction products are present in the aqueous solution in a concentration between about 1 to lOOOppm, more preferably between about 5 to 500 ppm, more preferably, between about 10 to lOOppm and most preferably between about 25 and 90ppm.
- the reaction products are present in the aqueous solution in a concentration of between about 55 to 75ppm.
- the reaction is quite rapid and the products liable to degrade, thus after contacting the reactants at room temperature, it is preferred that the resultant treatment is administered within about 3 to 4 hours.
- the peroxidase enzyme is removed from the reaction products formed from the peroxidase catalysed reaction by rendering it captive in a solid phase after the reaction has occurred.
- the enzyme may be rendered captive in a solid phase by an aggregate, which may be a coagulant, flocculant or emulsifier, which may be in the presence of one or more thickening agent.
- the peroxidase enzyme should be understood as optionally also referring to the support upon which the enzyme may be carried.
- the aggregate may be synthetic or naturally occurring.
- the aggregate may be Aluminium based.
- the aggregate may comprise chitosan, which may be derived from an extract of the exoskeleton of crustaceans such as shrimps or crabs for example.
- the enzyme is rendered captive in a solid phase by one or more flocculant.
- the one or more flocculant is selected from one or more of polymeric anionic or cationic flocculants, such as polysaccharides or polyacrylamides .
- the enzyme is rendered captive in a solid phase by one or more coagulants.
- reaction products of the reaction are the oxidised species (the product of oxidisation of the oxidisable species). Therefore, for example, if the oxidisable species is a thiocyanate ion, then the main active ingredient of the treatment is believed to be hypothiocyanate : [OSCN] " .
- a method of preparing a treatment comprising contacting at least one oxidisable species with at least one oxygen donor in the presence of a peroxidase enzyme and thereafter removing the peroxidase enzyme.
- kits for preparing a treatment comprising a source of an oxidisable species, a source of at least one oxygen donor and a peroxidase enzyme .
- the kit may further comprise at least one flocculating agent .
- the kit may further comprise a pH adjusting agent such as an acid, for example.
- the pH adjusting agent may adjust the pH of the aqueous solution to between 3 and 11.
- a pharmaceutical composition comprising an active ingredient and one or more inactive ingredient, the active ingredient consisting of the products formed from a peroxidase catalysed reaction between an oxidisable species and at least one oxygen donor.
- the one or more inactive ingredient may comprise a solvent .
- the active ingredient may consist of one or more of the following ions: [OSCN] “ ; [OF] “ ; [OCl] “ ; [OBr] “ ; [0I] “ .
- bacterial infections and bacterial infectious diseases include but are not restricted to the following: Anthrax; Bacterial Meningitis; Botulism; Brucellosis; Campylobacteriosis; Cat Scratch Disease; Cholera; Diphtheria; Epidemic Typhus; Gonorrhea; Impetigo; Legionellosis; Leprosy (Hansen's Disease); Leptospirosis; Listeriosis; Lyme Disease; Melioidosis; MRSA infection; Nocardiosis; Pertussis (Whooping Cough); Plague; Pneumococcal pneumonia; Psittacosis; Q fever; Rocky Mountain Spotted Fever (RMSF) ; Salmonellosis; Scarlet Fever; Shigellosis; Syphilis; Tetanus; Trachoma; Tuberculosis; Tularemia; Typhoid Fever; Typhus; Urinary Tract Infections; eye infections; gastric infections; lung infections; vaginosis.
- parasitic infections and parasitic infectious diseases include but are not restricted to the following: African trypanosomiasis; Amebiasis; Ascariasis; Babesiosis; Chagas Disease; Clonorchiasis; Cryptosporidiosis; Cysticercosis; Diphyllobothriasis; Dracunculiasis; Echinococcosis; Enterobiasis; Fascioliasis ; Fasciolopsiasis; Filariasis; Free-living amebic infection; Giardiasis; Gnathostomiasis; Hymenolepiasis; Isosporiasis; Kala-azar; Leishmaniasis; Malaria; Metagonimiasis; Myiasis; Onchocerciasis; Pediculosis; Pinworm Infection; Scabies; Schistosomiasis; Taeniasis; Toxocariasis; Toxoplasmosis
- fungal infections and fungal infectious diseases include but are not restricted to the following: Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Histoplasmosis; Tinea pedis .
- prionic infections and prionic infectious diseases include but are not restricted to the following: transmissible spongiform encephalopathy; Bovine spongiform encephalopathy; Creutzfeldt-Jakob disease; Kuru-Fatal Familial Insomnia; Alpers Syndrome.
- the infection is a respiratory system infection.
- the treatment is for mammalian infections, more preferably, human infections.
- the treatment is a respiratory system infection treatment.
- the treatment may be administered by adding the aqueous reaction products to a volume of air or an air stream, for example by humidification of air.
- a method of treatment of an infection comprising contaminating a volume of air or an air stream with the reaction products of a source of an oxidisable species and a source of an oxygen donor in the presence of a peroxidase enzyme, the peroxidase enzyme having been removed from the said reaction products, and exposing a patient to the said volume of air or air stream.
- reaction products of a source of an oxidisable species and a source of an oxygen donor in the presence of a peroxidase enzyme, the peroxidase enzyme having been removed from the said reaction products, in contaminating a volume of air or an air stream.
- the said reaction products are present as an aqueous mist in the volume of air or the air stream.
- the particle diameter of the mist droplets are less than 20 microns in size, more preferably less than 10 microns in size, more preferably between about 1 micron and 5 microns in size. Reference to size of vapour droplets refers to average particle diameter.
- the aqueous mist is prepared by ultrasound.
- Each studied strain has been extracted from its environment and identified as follows: Salmonella infantis, Escherichia coli, Staphylococcus aureus and Listeria monocytogenes .
- the strain Prior to the impact study, the strain (preserved at 4 0 C on nutrient agar) is planted out on trypcase-soy agar (Biomerieux) and incubated during 24h at 37 0 C.
- a bacterial suspension is made in sterile physiological water from the planting out on a solid medium, so as to obtain a suspension from 10 5 to 10 7 CFU/ml.
- a sterile bottle is filled up with drinkable water, i.e. a process water without OSCN " ions (negative control bottle) . Five of those are also prepared for each studied strain .
- drinkable water i.e. a process water without OSCN " ions (negative control bottle) .
- Five of those are also prepared for each studied strain .
- T 0 20 ⁇ l of bacterial suspension was added to each bottle.
- the number of CFU/ml in the reaction medium for each bottle from T 0 to T+xmin (at ambient temperature i.e. ⁇ 2O 0 C) was determined by counting on the surface of the trypcase-soy solid medium (5 analyses per bottle until the dilution is sufficient to count the number of microorganisms) and incubating during 24h at 37 0 C.
- the total count (0,1 ml spreading) was performed after having neutralized OSCN " ions by mixing 1 ml of the suspension to be counted with 1 ml of neutralizing solution, i.e. 2 mM cysteine able to neutralize OSCN " up to a concentration of 1000 ⁇ M. This is done for each collecting time and each bottle (negative control included) .
- This value is the one used to define the level of population in each bottle.
- defining the population in the bottles containing OSCN " ions at To would imply to instantly neutralize active ions after the introduction of the inoculum, which is technically very difficult.
- the count of CFU/plate after 24h of incubation at 37 0 C allows us to determine the evolution of the microbial population in the reaction medium for each type of treatment (various concentrations) in relation to the contact time with the active principle (OSCN " ions) .
- OSCN content is determined in the reaction medium just before inserting the bacterial inoculum, in order to know precisely the concentration of active principle, which the microorganism population will be exposed to.
- a kit may be provided from which the treatment may be manufactured in the home or where required.
- Such a kit has a long life span and is easily transportable .
- Lactoperoxidase enzyme (on a bentonite support) 1. Og Coagulant (Aluminium polychlorosulphate) 0.0011
- Such a kit may be used to produce a 500ml aqueous solution of 35ppm OSCN " as follows.
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Abstract
A treatment for an infection, the treatment comprising the products formed from a peroxidase catalysed reaction between an oxidisable species and at least one oxygen donor, in aqueous solution; wherein the original enzyme has been removed therefrom.
Description
A Treatment
The present invention relates to a treatment, a method of preparing the same and a kit for preparing the same.
Infection is caused by a foreign species colonizing in a host organism and utilizing the hosts resources in order to multiply. Infections can have severe detrimental effects in the host including inflammation of the infected area which can lead in some cases to severe trauma to the host and even death. Infections can be bacterial, parasitic, fungal or prionic. Common infections that may affect humans include: cholera, leprosy and bubonic plague, E. CoIi, Salmonella, MRSA and infections due to genetic immune deficiencies.
Commonly, anti-infection agents are used to treat infections by killing or preventing the growth of the foreign species without harming the host. Many different anti-infection agents have been developed and are effective against different foreign species, but can have a detrimental effect on the host.
It is an aim of objects of the present invention to provide an alternative anti-infection agent that does not have a detrimental effect on the host and a treatment for one or more infection.
According to a first aspect of the present invention there is provided a treatment for an infection, the treatment comprising the products formed from a peroxidase catalysed reaction between an oxidisable species and at least one oxygen donor, in aqueous
solution; wherein the original peroxidase enzyme has been removed therefrom.
The infection may be a bacterial infection (an infection caused by one or more bacterium) ; a parasitic infection (an infection caused by one or more parasite) ; a fungal infection (an infection caused by one or more fungus); and/or a prionic infection (an infection caused by one or more prion) .
The treatment may be orally administrable, topically administrable, administrable as a wash or douche, or administrable by inhalation. The treatment may be orally administrable as an aqueous solution.
The treatment may be administered topically or orally by any of a spray, a gel, a bath, a wetted cloth.
The treatment may be administered by inhalation by spray, humidified air or fog.
For the avoidance of doubt, the term "treatment" as used herein refers to a pharmaceutical composition.
Preferably, the oxidisable species comprises any species operable to be oxidised by the oxygen donor in the presence of a peroxidase enzyme.
In one embodiment, the oxidisable species may comprise a source of thiocyanate ions. The source of thiocyanate ions may be any substance that provides free thiocyanate ions in aqueous solution, for example a metal salt thereof such as any of a sodium, potassium, lithium salt etc. Alternatively, the source of thiocyanate ions may be
derived from hydrogen thiocyanate . In one embodiment, the source of thiocyanate ions may be as reaction products of a further reaction.
For the avoidance of doubt, reference herein to thiocyanate ions means [SCN]" ions.
In an alternative embodiment, the oxidisable species may comprise a source of halide ions. The source of halide ions may be any substance that provides free halide ions in aqueous solution, for example a metal halide salt. The source of halide ions may comprise a source of one or more of fluoride ions, chloride ions, bromide ions or iodide ions. Suitable metal salts include any halide salt that readily dissociates in aqueous solution to provide the free halide ion. For example, the salt may be a group I metal salt such as lithium, sodium, potassium etc .
Preferably, the treatment further comprises an amount of the oxidisable species. For example, the treatment may comprises the products formed from a peroxidase catalysed reaction between an oxidisable species and at least one oxygen donor, in aqueous solution; and an amount of unreacted oxidisable species. Preferably, the oxidisable species is present in the treatment in an amount (by mol) in excess of the said formed products. Preferably, the ratio of the oxidisable species present in the treatment to the amount of the said formed products is at least about 1.1:1 (by mol), more preferably at least about 1.2:1 (by mol), more preferably at least about 1.3:1 (by mol), most preferably at least about 1.4:1. In a particularly preferred embodiment, the ratio of the
oxidisable species present in the treatment to the amount of the said formed products is about 1.5:1 (by mol) .
In one embodiment, the oxidisable species may be [SCN]" and the said formed products may comprise [OSCN]". In such a scenario, [SCN]" is present in the treatment in an amount (by mol) in excess of the [OSCN]".
Alternatively, the oxidisable species present in the treatment may be different to the oxidisable species from which the said formed products are derived. For example, the oxidisable species from which the said products are formed may be [SCN]", whereas the oxidisable species present in the treatment may be a source of halide ions, such as Cl", for example.
The source of the oxidisable species may be present in the reactants (prior to the peroxidase catalysed reaction) in a concentration such that the oxidisable species in the reactants is present in the aqueous solution at a concentration of about 0.1 to 5OmM. More preferably, about 0.5 to 1OmM, more preferably between about 1 and 5mM. In a most preferred embodiment, about 2mM.
Preferably, the at least one oxygen donor comprises a source of peroxide.
The source of peroxide may be any entity that comprises the group X-O-O-Y, where 0 represents an oxygen radical. In one embodiment, one of or both of X and Y may be hydrogen. For example, the source of peroxide may be hydrogen peroxide.
Either of X and/or Y may represent a chemical species, such as an organic fragment or, in one embodiment, may represent a surface to which the -0-0- group is bound. If X and/or Y represents a surface to which the -0-0- group is bound, then a linking group between the -0-0- group and the surface may be present, such as a bivalent organic bridging group, for example. Alternatively, X and/or Y may represent an inorganic species, such as magnesium, sodium etc.
The source of peroxide may be present in the reactants
(prior to the peroxidase catalysed reaction) in a concentration such that the peroxide species in the reactants in aqueous solution is present at a concentration of about 0.1 to 5OmM. More preferably, about 0.5 to 1OmM, more preferably between about 1 and 5mM.
In one embodiment, the source of peroxide may be an organic peroxide compound or salt thereof.
Preferably, the peroxidase enzyme is a lactoperoxidase enzyme .
The lactoperoxidase may be naturally occurring lactoperoxidase, for example as extracted from milk. Alternatively, the lactoperoxidase may be artificially synthesised.
Preferably, the peroxidase enzyme is provided on one or more support. Preferably, the support is an inorganic clay material. For example, the support may comprise bentonite .
Preferably, the peroxidase enzyme is present in the reactants (prior to the peroxidase catalysed reaction) in an amount of between about 0.001 to 10 g/1. More preferably, 0.005 to 5 g/1.
Preferably, the peroxidase enzyme is present in the treatment in an amount less than about 0.001 g/1. More preferably, the peroxidase enzyme is present in the treatment in an amount less than about 0.0005g/l. More preferably, the peroxidase enzyme is present in the treatment in an amount less than about O.OOOlg/1. More preferably, the peroxidase enzyme is present in the treatment in an amount less than about O.OOOOlg/1.
Preferably, the treatment comprises substantially no peroxidase enzyme therein.
The reaction can occur over a range of pH depending on the desired use of the resulting active species. For example, the reaction can occur between pH 3 and pH 11 (measured at 250C) . In a preferred embodiment, the reaction takes place between pH 4 and pH 10 (measured at 250C) .
Preferably, the reaction is performed in a temperature range between 20C and 6O0C. However, it should be noted that the stability of the oxidised products is temperature dependent and therefore a temperature may be chosen to correspond with the intended use. For example, at higher temperatures, the stability of the oxidised species is lower (and therefore degrades faster) than at lower temperatures.
Preferably, the reaction products (the oxidised species) are present in the aqueous solution in a concentration
between about 1 to lOOOppm, more preferably between about 5 to 500 ppm, more preferably, between about 10 to lOOppm and most preferably between about 25 and 90ppm. In a most preferred embodiment, the reaction products (the oxidised species) are present in the aqueous solution in a concentration of between about 55 to 75ppm.
The reaction is quite rapid and the products liable to degrade, thus after contacting the reactants at room temperature, it is preferred that the resultant treatment is administered within about 3 to 4 hours.
In a preferred embodiment, the peroxidase enzyme is removed from the reaction products formed from the peroxidase catalysed reaction by rendering it captive in a solid phase after the reaction has occurred. For example, the enzyme may be rendered captive in a solid phase by an aggregate, which may be a coagulant, flocculant or emulsifier, which may be in the presence of one or more thickening agent.
Reference herein to "the peroxidase enzyme" should be understood as optionally also referring to the support upon which the enzyme may be carried.
The aggregate may be synthetic or naturally occurring. The aggregate may be Aluminium based. The aggregate may comprise chitosan, which may be derived from an extract of the exoskeleton of crustaceans such as shrimps or crabs for example.
Preferably, the enzyme is rendered captive in a solid phase by one or more flocculant. Preferably, the one or more flocculant is selected from one or more of polymeric
anionic or cationic flocculants, such as polysaccharides or polyacrylamides .
Preferably, the enzyme is rendered captive in a solid phase by one or more coagulants.
It is believed that the reaction products of the reaction are the oxidised species (the product of oxidisation of the oxidisable species). Therefore, for example, if the oxidisable species is a thiocyanate ion, then the main active ingredient of the treatment is believed to be hypothiocyanate : [OSCN]".
According to a further aspect of the present invention, there is provided a method of preparing a treatment, the method comprising contacting at least one oxidisable species with at least one oxygen donor in the presence of a peroxidase enzyme and thereafter removing the peroxidase enzyme.
According to a further aspect of the present invention there is provided a kit for preparing a treatment, the kit comprising a source of an oxidisable species, a source of at least one oxygen donor and a peroxidase enzyme .
The kit may further comprise at least one flocculating agent .
The kit may further comprise a pH adjusting agent such as an acid, for example. The pH adjusting agent may adjust the pH of the aqueous solution to between 3 and 11.
According to a further aspect of the present invention there is provided a use of the reaction products of a source of an oxidisable species and a source of an oxygen donor in the presence of a peroxidase enzyme, the reaction products having been separated from the peroxidase enzyme, in the treatment of an infection.
According to a further aspect of the present invention there is provided a pharmaceutical composition comprising an active ingredient and one or more inactive ingredient, the active ingredient consisting of the products formed from a peroxidase catalysed reaction between an oxidisable species and at least one oxygen donor.
The one or more inactive ingredient may comprise a solvent .
The active ingredient may consist of one or more of the following ions: [OSCN]"; [OF]"; [OCl]"; [OBr]"; [0I]".
Examples of bacterial infections and bacterial infectious diseases include but are not restricted to the following: Anthrax; Bacterial Meningitis; Botulism; Brucellosis; Campylobacteriosis; Cat Scratch Disease; Cholera; Diphtheria; Epidemic Typhus; Gonorrhea; Impetigo; Legionellosis; Leprosy (Hansen's Disease); Leptospirosis; Listeriosis; Lyme Disease; Melioidosis; MRSA infection; Nocardiosis; Pertussis (Whooping Cough); Plague; Pneumococcal pneumonia; Psittacosis; Q fever; Rocky Mountain Spotted Fever (RMSF) ; Salmonellosis; Scarlet Fever; Shigellosis; Syphilis; Tetanus; Trachoma; Tuberculosis; Tularemia; Typhoid Fever; Typhus; Urinary
Tract Infections; eye infections; gastric infections; lung infections; vaginosis.
Examples of parasitic infections and parasitic infectious diseases include but are not restricted to the following: African trypanosomiasis; Amebiasis; Ascariasis; Babesiosis; Chagas Disease; Clonorchiasis; Cryptosporidiosis; Cysticercosis; Diphyllobothriasis; Dracunculiasis; Echinococcosis; Enterobiasis; Fascioliasis ; Fasciolopsiasis; Filariasis; Free-living amebic infection; Giardiasis; Gnathostomiasis; Hymenolepiasis; Isosporiasis; Kala-azar; Leishmaniasis; Malaria; Metagonimiasis; Myiasis; Onchocerciasis; Pediculosis; Pinworm Infection; Scabies; Schistosomiasis; Taeniasis; Toxocariasis; Toxoplasmosis; Trichinellosis; Trichinosis; Trichuriasis; Trichomoniasis; Trypanosomiasis ; Deznutziolisis .
Examples of fungal infections and fungal infectious diseases include but are not restricted to the following: Aspergillosis; Blastomycosis; Candidiasis; Coccidioidomycosis; Cryptococcosis; Histoplasmosis; Tinea pedis .
Examples of prionic infections and prionic infectious diseases include but are not restricted to the following: transmissible spongiform encephalopathy; Bovine spongiform encephalopathy; Creutzfeldt-Jakob disease; Kuru-Fatal Familial Insomnia; Alpers Syndrome.
Preferably, the infection is a respiratory system infection. Preferably, the treatment is for mammalian infections, more preferably, human infections. Preferably, the treatment is a respiratory system infection treatment.
According to a further aspect of the present invention there is provided a use of the reaction products of a source of an oxidisable species and a source of an oxygen donor in the presence of a peroxidase enzyme for the manufacture of a medicament for the treatment of an infection .
The treatment may be administered by adding the aqueous reaction products to a volume of air or an air stream, for example by humidification of air.
Therefore, according to a further aspect of the present invention there is provided a method of treatment of an infection comprising contaminating a volume of air or an air stream with the reaction products of a source of an oxidisable species and a source of an oxygen donor in the presence of a peroxidase enzyme, the peroxidase enzyme having been removed from the said reaction products, and exposing a patient to the said volume of air or air stream.
According to a further aspect of the present invention there is provided a use of the reaction products of a source of an oxidisable species and a source of an oxygen donor in the presence of a peroxidase enzyme, the peroxidase enzyme having been removed from the said
reaction products, in destroying airborne infection causing organisms.
In a further embodiment of the present invention there is provided the use of the reaction products of a source of an oxidisable species and a source of an oxygen donor in the presence of a peroxidase enzyme, the peroxidase enzyme having been removed from the said reaction products, in contaminating a volume of air or an air stream.
Preferably, the said reaction products are present as an aqueous mist in the volume of air or the air stream. Preferably, the particle diameter of the mist droplets are less than 20 microns in size, more preferably less than 10 microns in size, more preferably between about 1 micron and 5 microns in size. Reference to size of vapour droplets refers to average particle diameter.
Preferably, the aqueous mist is prepared by ultrasound.
All of the features disclosed herein may be combined with any of the above aspects and in any combination.
For a better understanding of the invention, and to show how embodiments of the same may be carried into effect, reference will now be made, by way of example only, to the following experimental data.
Experimental
Each studied strain has been extracted from its environment and identified as follows: Salmonella
infantis, Escherichia coli, Staphylococcus aureus and Listeria monocytogenes .
Making the bacterial suspension:
Prior to the impact study, the strain (preserved at 40C on nutrient agar) is planted out on trypcase-soy agar (Biomerieux) and incubated during 24h at 370C.
On the day of study, a bacterial suspension is made in sterile physiological water from the planting out on a solid medium, so as to obtain a suspension from 105 to 107 CFU/ml.
Assessing the efficiency of the process on bacterial strains
For each studied strain and concentration (3 concentrations between 100 μM and 700 μM OSCN") , five sterile bottles are filled up with 200 ml of OSCN" solution produced by exposing a source of thiocyanate and a source of H2O2 to a lactoperoxidase enzyme on a bentonite carrier, followed by adding a flocculant, aluminium polychlorosulphate, to flocculate the enzyme and carrier, before filtering the resulting aqueous solution. Washing water is at 120C and the pH is adjusted with lactic acid at 7 ±0,05.
A sterile bottle is filled up with drinkable water, i.e. a process water without OSCN" ions (negative control bottle) . Five of those are also prepared for each studied strain .
At T0, 20 μl of bacterial suspension was added to each bottle. The number of CFU/ml in the reaction medium for each bottle from T0 to T+xmin (at ambient temperature i.e. ~ 2O0C) was determined by counting on the surface of the trypcase-soy solid medium (5 analyses per bottle until the dilution is sufficient to count the number of microorganisms) and incubating during 24h at 370C.
The total count (0,1 ml spreading) was performed after having neutralized OSCN" ions by mixing 1 ml of the suspension to be counted with 1 ml of neutralizing solution, i.e. 2 mM cysteine able to neutralize OSCN" up to a concentration of 1000 μM. This is done for each collecting time and each bottle (negative control included) .
It is to be noted that the initial population (T0) is only determined in the negative control bottle as the variability between bottles is very little (maximum observed coefficient of variation = 15%) . This value is the one used to define the level of population in each bottle. Besides, defining the population in the bottles containing OSCN" ions at To would imply to instantly neutralize active ions after the introduction of the inoculum, which is technically very difficult.
The count of CFU/plate after 24h of incubation at 370C allows us to determine the evolution of the microbial population in the reaction medium for each type of treatment (various concentrations) in relation to the contact time with the active principle (OSCN" ions) .
Determination of OSCN" ions in the reaction medium :
The measure is performed with a spectrophotometry technique at 412nm.
OSCN" content is determined in the reaction medium just before inserting the bacterial inoculum, in order to know precisely the concentration of active principle, which the microorganism population will be exposed to.
Impact studies
Impact study of OSCN solutions on a population of Escherichia coli
The table below gives the various OSCN concentrations tested and the evolution of the population in CFU/ml = f (exposure time) for each type of treatment.
Neg.
Designation. & B C COΩtrol
22 O± 5 463± 4 630± 7 0
CFtJ/ml at- 0 min NM NM NM 370 ± 21
CFtJ/ml at- 5- min 325 ± 50 60 ± 20 30 ± 15 NM
CFtJ/ml at 15
301 ± 37 10 ± 3 2 ± 1 NM min
CFU/ml at 30
250 ± 63 0 0 NM min
CFtJ/ml at 60
190 ± 27 0 0 330 ± 83 min
Results in CFU/ml ± standard deviation (n=5] NM: Not Measured
Impact study of OSCN on a population of Salmonella infantis
Impact on a 103 CFU/ml population
The table below gives the various OSCN" concentrations tested and the evolution of the population in CFU/ml = f (exposure time) for each type of treatment.
Results in CFU/ml ± standard deviation (n=5] NM: Not Measured
Impact on a 102 CFU/ml population
£Jeg<
D^signation B C control
[GSCJsT] Tt) 240± 8 402± 7 588± 8 0
CFU/ml at 0 mi.ύ. NM NM NM 970 ± 71
CFU/ml at 5 min. 185 ± 112 15± 5 10 ± 4 NM
CFU/ml at 15 min 35 ± 18 2+ 1 0 NM
CFU/ml at 30 min 15 ± 5 0 0 890 ± 139
Results in CFU/ml ± standard deviation (n=5^
NM: Not Measured
Impact study of OSCN solutions on a population of Staphylococcus aureus
The table below gives the various OSCN" concentrations tested and the evolution of the population in CFU/ml = f (exposure time) for each type of treatment.
Results in CFU/ml ± standard deviation (n=5] NM: Not Measure d
Impact study of OSCN solutions on a population of Listeria monocytogene
Impact on a 103 CFU/ml population
The table below gives the OSCN" concentration tested and the evolution of the population in CFU/ml = f (exposure time) for each treatment and the negative control.
Results in CFU/ml ± standard deviation (n=5) NM: Not Measured
Impact on a 102 CFU/ml population
The table below gives the OSCN concentration tested and the evolution of the population in CFU/ml = f (exposure time) for each treatment and the negative control.
Results in CFU/ml ± standard deviation (n=5] NM: Not Measured
A treatment made in accordance with the present invention offers a quick and simple to prepare medicament that may be used to treat a wide range of infections.
Advantageously, a kit may be provided from which the treatment may be manufactured in the home or where required. Such a kit has a long life span and is easily transportable .
An example of such a kit is as follows:
Lactoperoxidase enzyme (on a bentonite support) 1. Og Coagulant (Aluminium polychlorosulphate) 0.0011
Sodium thiocyanate
0.062g
Hydrogen peroxide 0.00751 of
100%
Such a kit may be used to produce a 500ml aqueous solution of 35ppm OSCN" as follows.
500ml of water is added to a jug followed by adding the enzyme thereto and stirring. The Sodium thiocyanate is then added during continuous stirring. Hydrogen peroxide is next added during continuous stirring before adding the coagulant and stirring for a further 5 minutes. The mixture is then left for about 30 minutes, during which time flocculation occurs and the solid settles to the bottom of the container. The aqueous solution is then poured into a separate receptacle through filter paper and is ready to be used as a treatment, for example by drinking .
Although the above preparation prepares a aqueous solution of 35ppm [OSCN]-, it will be appreciated that by changing the concentration of reagents a different concentration may be prepared, in accordance with the preferred ranges stated above.
Attention is directed to all papers and documents which are filed concurrently with or previous to this specification in connection with this application and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference.
All of the features disclosed in this specification (including any accompanying claims, abstract and drawings), and/or all of the steps of any method or process so disclosed, may be combined in any combination, except combinations where at least some of such features and/or steps are mutually exclusive.
Each feature disclosed in this specification (including any accompanying claims, abstract and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.
The invention is not restricted to the details of the foregoing embodiment (s) . The invention extends to any novel one, or any novel combination, of the features disclosed in this specification (including any accompanying claims, abstract and drawings), or to any
novel one, or any novel combination, of the steps of any method or process so disclosed.
Claims
1. A treatment for an infection, the treatment comprising the products formed from a peroxidase catalysed reaction between an oxidisable species and at least one oxygen donor, in aqueous solution; wherein the original enzyme has been removed therefrom.
2. A treatment according to claim 1 wherein the infection is a bacterial infection (an infection caused by one or more bacterium) ; a parasitic infection (an infection caused by one or more parasite) ; a fungal infection (an infection caused by one or more fungus); and/or a prionic infection (an infection caused by one or more prion) .
3. A treatment according to claim 1 or 2 wherein the treatment is orally administrable, topically administrable, administrable as a wash or douche, or administrable by inhalation.
4. A treatment according to any preceding claim, wherein the treatment is orally administrative as an aqueous solution.
5. A treatment according to any preceding claim, wherein the treatment is administered topically by any of a spray, a gel, a bath, a wetted cloth.
6. A treatment according to any preceding claim, wherein the treatment may be administered by inhalation by spray, humidified air or fog.
7. A treatment according to any preceding claim wherein the oxidisable species comprises any species operable to be oxidised by the oxygen donor in the presence of a peroxidase enzyme.
8. A treatment according to any preceding claim wherein the oxidisable species comprises a source of thiocyanate ions.
9. A treatment according to claim 8, wherein the source of thiocyanate ions comprises any substance that provides free thiocyanate ions in aqueous solution, for example a metal salt thereof such as any of a sodium, potassium, lithium salt etc.
10. A treatment according to claim 8 wherein the source of thiocyanate ions is derived from hydrogen thiocyanate .
11. A treatment according to claim 8 wherein the source of thiocyanate ions is provided as reaction products of a further reaction.
12. A treatment according to claim 1 to 7 wherein the oxidisable species comprises a source of halide ions .
13. A treatment according to claim 12 wherein the source of halide ions is any substance that provides free halide ions in aqueous solution, for example a metal halide salt.
14. A treatment according to claim 12 or 13 wherein the source of halide ions comprises a source of one or more of fluoride ions, chloride ions, bromide ions or iodide ions.
15. A treatment according to claim 12 to 14 wherein suitable metal salts include any halide salt that readily dissociates in aqueous solution to provide the free halide ion.
16. A treatment according to claim 12 to 15 wherein the salt is a group I metal salt such as lithium, sodium, potassium etc.
17. A treatment according to any preceding claim wherein the source of the oxidisable species is present in the reactants (prior to the peroxidase catalysed reaction) in a concentration such that the oxidisable species in the reactants is present in the aqueous solution at a concentration of about 0.1 to 5OmM.
18. A treatment according to any preceding claim wherein the at least one oxygen donor comprises a source of peroxide.
19. A treatment according to claim 18, wherein the source of peroxide is any entity that comprises the group X-O-O-Y, where 0 represents an oxygen radical .
20. A treatment according to claim 19, wherein one of or both of X and Y are hydrogen.
21. A treatment according to claim 19 wherein either of X and/or Y represent a chemical species, such as an organic fragment or, in one embodiment, represent a surface to which the -0-0- group is bound.
22. A treatment according to claim 19 wherein X and/or Y represent an inorganic species, such as magnesium, sodium etc.
23. A treatment according to claim 18 to 22 wherein the source of peroxide is present in the reactants (prior to the peroxidase catalysed reaction) in a concentration such that the peroxide species in the reactants in aqueous solution is present at a concentration of about 0.1 to 5OmM.
24. A treatment according to claim 18 to 23 wherein the source of peroxide is an organic peroxide compound or salt thereof.
25. A treatment according to any preceding claim, wherein the peroxidase enzyme is a lactoperoxidase enzyme .
26. A treatment according to claim 25, wherein lactoperoxidase is naturally occurring lactoperoxidase, for example as extracted from milk .
27. A treatment according to claim 25 wherein the lactoperoxidase has been synthesised artificially.
28. A treatment according to any preceding claim wherein the peroxidase enzyme is provided on one or more support .
29. A treatment according to claim 28, wherein the support is an inorganic clay material.
30. A treatment according to any preceding claim, wherein the peroxidase enzyme is present in the reactants (prior to the peroxidase catalysed reaction) in an amount of between about 0.001 to 10 g/i
31. A treatment according to any preceding claim wherein the peroxidase catalysed reaction occurs between pH 3 and pH 11 (measured at 250C) .
32. A treatment according to any preceding claim wherein the peroxidase catalysed reaction is performed in a temperature range between 20C and 6O0C.
33. A treatment according to any preceding claim wherein the peroxidase catalysed reaction products (the oxidised species) are present in the aqueous solution in a concentration between about 1 to lOOOppm.
34. A treatment according to any preceding claim wherein the enzyme is removed from the treatment following the peroxidase catalysed reaction by rendering the enzyme captive in a solid phase.
35. A treatment according to claim 34, wherein the enzyme is rendered captive in a solid phase by an aggregate, which may be a coagulant, flocculant or emulsifier, which may be in the presence of one or more thickening agent.
36. A method of preparing a treatment, the method comprising contacting at least one oxidisable species with at least one oxygen donor in the presence of a peroxidase enzyme and thereafter removing the peroxidase enzyme.
37. A kit for preparing a treatment, the kit comprising a source of an oxidisable species, a source of at least one oxygen donor and a peroxidase.
38. A kit according to claim 37 wherein the kit further comprise at least one flocculating agent.
39. A kit according to claim 37 or 38, wherein the kit further comprises a pH adjusting agent such as an acid, for example.
40. Use of the reaction products of a source of an oxidisable species and a source of an oxygen donor in the presence of a peroxidase enzyme; the peroxidase enzyme having been removed from the products, in the treatment of an infection.
41. A treatment according to any of claims 1 to 35 wherein the treatment is for mammalian infections, more preferably, human infections.
42. Use of the reaction products of a source of an oxidisable species and a source of an oxygen donor in the presence of a peroxidase enzyme, the peroxidase enzyme having been removed from the products, for the manufacture of a medicament for the treatment of an infection.
43. A method of treatment of an infection comprising contaminating an air stream with the reaction products of a source of an oxidisable species and a source of an oxygen donor in the presence of a peroxidase enzyme, the peroxidase enzyme having been removed from the products, and exposing a patient to that said air stream.
44. Use of the reaction products of a source of an oxidisable species and a source of an oxygen donor in the presence of a peroxidase enzyme, the peroxidase enzyme having been removed from the products, in destroying airborne infection causing organisms .
45. Use of the reaction products of a source of an oxidisable species and a source of an oxygen donor in the presence of a peroxidase enzyme, the peroxidase enzyme having been removed from the products, in contaminating an air stream.
46. A treatment, substantially as herein before described and with reference to the examples.
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002682145A CA2682145A1 (en) | 2007-03-23 | 2008-03-25 | A treatment |
EP08719060A EP2124971A2 (en) | 2007-03-23 | 2008-03-25 | Treatments for bacterial, parasitic, fungal and prionic infections |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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GBGB0705557.7A GB0705557D0 (en) | 2007-03-23 | 2007-03-23 | A treatment |
GB0705557.7 | 2007-03-23 |
Publications (2)
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WO2008117091A2 true WO2008117091A2 (en) | 2008-10-02 |
WO2008117091A3 WO2008117091A3 (en) | 2009-04-23 |
Family
ID=38024667
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB2008/050213 WO2008117089A2 (en) | 2007-03-23 | 2008-03-25 | Treatments for viral infections |
PCT/GB2008/050215 WO2008117091A2 (en) | 2007-03-23 | 2008-03-25 | Treatments for bacterial, parasitic, fungal and prionic infections |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/GB2008/050213 WO2008117089A2 (en) | 2007-03-23 | 2008-03-25 | Treatments for viral infections |
Country Status (4)
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EP (1) | EP2124971A2 (en) |
CA (1) | CA2682145A1 (en) |
GB (1) | GB0705557D0 (en) |
WO (2) | WO2008117089A2 (en) |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8515079D0 (en) * | 1985-06-14 | 1985-07-17 | Kellway Pharma | Contact lens cleaning & disinfection |
GB9015910D0 (en) * | 1990-07-19 | 1990-09-05 | Univ Bruxelles | Novel use |
EP0745327A1 (en) * | 1995-05-29 | 1996-12-04 | Symbollon Corporation | Method for inactivating pathogens |
SE506529C2 (en) * | 1996-01-23 | 1997-12-22 | Semper Ab | Use of a lactoperoxidase system for the preparation of a drug against Helicobacter pylori |
FR2798137A1 (en) * | 1999-09-07 | 2001-03-09 | Bonneau Marguerite Gabr Calone | GENERATING APPARATUS FOR OXYGENIC CHEMICAL RADICALS AND INDUSTRIAL APPLICATIONS |
US6592890B1 (en) * | 1999-10-20 | 2003-07-15 | Oxibio, Inc. | Conveyance of anti-infective activity to wound dressings |
WO2002069958A1 (en) * | 2001-03-01 | 2002-09-12 | Wolfgang Weuffen | Thiocyanate ions for preventing and treating bse and similar animal and human diseases |
US6702998B2 (en) * | 2001-05-15 | 2004-03-09 | Gregory E. Conner | Methods and devices for treating lung dysfunction |
FR2825373B1 (en) * | 2001-05-31 | 2004-04-30 | Tmi Europ | PROCESS FOR THE ENZYMATIC PRODUCTION OF A FLUID TREATMENT AGENT |
JP4355592B2 (en) * | 2004-02-23 | 2009-11-04 | 森永乳業株式会社 | Antiviral agent |
-
2007
- 2007-03-23 GB GBGB0705557.7A patent/GB0705557D0/en not_active Ceased
-
2008
- 2008-03-25 WO PCT/GB2008/050213 patent/WO2008117089A2/en active Application Filing
- 2008-03-25 CA CA002682145A patent/CA2682145A1/en not_active Abandoned
- 2008-03-25 WO PCT/GB2008/050215 patent/WO2008117091A2/en active Application Filing
- 2008-03-25 EP EP08719060A patent/EP2124971A2/en not_active Withdrawn
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EP2124971A2 (en) | 2009-12-02 |
CA2682145A1 (en) | 2008-10-02 |
WO2008117091A3 (en) | 2009-04-23 |
WO2008117089A3 (en) | 2009-04-23 |
WO2008117089A2 (en) | 2008-10-02 |
GB0705557D0 (en) | 2007-05-02 |
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