WO2006109069A1 - Use of a metal ion chelating agent for the treatment of animal and human parasites - Google Patents
Use of a metal ion chelating agent for the treatment of animal and human parasites Download PDFInfo
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- WO2006109069A1 WO2006109069A1 PCT/GB2006/001350 GB2006001350W WO2006109069A1 WO 2006109069 A1 WO2006109069 A1 WO 2006109069A1 GB 2006001350 W GB2006001350 W GB 2006001350W WO 2006109069 A1 WO2006109069 A1 WO 2006109069A1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
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- 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
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/04—Amoebicides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
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- 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
- This invention relates to manufacture and applications of metal ion chelating compositions for the treatment of parasitic nematodes and (other) parasitic organisms which include the protozoan species and others in human and non-human animals; including horses, sheep, cattle, cats, and dogs .
- nematodes There are many thousands of nematodes and whilst there are some 15,000 known species, there are thousands that occur even in a handful of soil; with a substantial number not yet named. They are prolific breeders with some containing many millions of eggs and laying up to 200,000 eggs per day.
- various parasitic nematodes that affect animals which may be mentioned are lungworms, whipworms, hookworms, threadworms, toxocara, and various filarial parasites.
- Other parasitic organisms in animals include, cestodes, notably tapeworms, and Bots.
- a nematode typically has a long and narrow body, in some cases resembling a thread and the epidermis is a mass of cellular material and nuclei without separate membranes.
- This epidermis establishes a thick outer layer called the cuticle, which is very tough and flexible.
- the cuticle which is very tough and flexible.
- Under the epidermis lie long muscles, which are aligned longitudinally, and this allows the nematode to bend its body from side to side. These muscles are activated by two nerves along its dorsal and ventral side.
- the nematode can either feed through its head or various openings along its body where it can draw food in, crush it and then digest it. Waste is removed through excretory canals, which are on each side of the body.
- the blood sucking varieties can consume up to O.lmls of blood per day and with several thousand present in an animal drawing blood it can result in the infested animal having a lethargic condition.
- a large family of parasitic nematodes (mainly round worms although flat worms may be present as well) inhabit the gut and intestinal passages of the animals and if not treated can lead to the occurrence of adverse medical and physical conditions.
- nematodes can suspend their life processes when conditions become unfavourable, for example they can survive extreme drying, heat or cold and then commence life at a later stage; a condition known as cryptobiosis .
- Parasitic nematodes in animals will result in the animal becoming thin and in some extreme cases if the animal is not treated for nematodes, it will die from malnutrion as the nematodes compete for nutrition from what the animal eats and tries to digest .
- the animals that experience parasites and parasitic nematodes are mainly horses, cattle and sheep, although companion animals (pets) do experience infestation to a degree .
- the main varieties that may be present are, Telodorsagia circumcinta, Trichostrongylus colubriformis, Haemonchus contortus ( Barber's pole or wire worm-blood sucker) , Ostertagia sp . up to several species of lungworm (Dictyocaulus filana) , tapeworms (Moniezia expansa) and at the same time, liver flukes - mainly Fasciola hepatica (a flatworm) .
- Oxyuris equi pin worms
- Tarascaris Equorum round worms
- Stongylus equines Str ⁇ ngylus edentatus (large)
- Strongylus vularis small
- Haemonchus contortus blood suckers
- the parasitic hookworm nematodes are Ancylostoma duodenale, and Toxocara canis in dogs and Ancylostoma tubeforme, and Toxocara cati in cats.
- parasitic nematodes go through various cycles of life within the animal and they may be present as eggs, larvae or fully-grown nematodes. When present in the gut and intestines of the animal they lodge in the gut wall and intestinal wall tissue and can live there for an indefinite period of time, adversely affecting the animal concerned. They control the growth of young animals as with parasitic nematodes being present nutrition is denied to the growing animal .
- Moxidectin Microcyclic Lactone - affects the chloride channels in the nervous system
- Ivermectin (Macrocyclic Lactone - binds to the glutamate gated chloride channels in the parasites nervous system)
- Oxibendazole Benzimidazole family- binds to tubulin subunit and interferes with microtubule formation
- Fenbendzole Benzididazole family - interferes with the nervous system
- Pyrantel pamoate Imidazothiazole - acts as a blocking agent on muscle activity
- Parasitic nematodes and parasites have, over a period of time, started to become resistant to the action of these chemicals with the result that they are no longer effective in treating animals for these conditions at the set dosage rate. If the dosage rate were to be increased to overcome the resistance problems, the toxicity of a lot of these chemicals would exceed the safe limits imposed for the treatment of animals so this is clearly not a realistic option.
- the Protozoan's that may be present are Amoeba and flagellates, Trichomonas vaginalis, Acanthamoeba, Giardia, Cryptosporidium, Entamoeba, Isospora, Balantidium Equine Protozoal Myeloencephalitis, Coccidia, Leishmania, Trypanosoma, Naegleria, Toxoplasma and
- Brucella may be present in animals as Brucella abortus, in seals as Brucella maris and in humans as Brucellosis.
- Parasitic Protozoan's and Brucella depend on Ferric and/or Ferrous ions and in all cases they enter the bloodstream to have access to the red blood cells to survive.
- Trichomonas protozoan With Trichomonas protozoan, this can be present in equines to an extent as a sexually transmitted disease and the female equine will be emitting a white secretion from the genital tract, as well as losing weight and if the animal is used for breeding it will not become pregnant with this condition present.
- Trichomonas vaginalis is treated as a sexually transmitted disease and if not treated, it produces various medical conditions within the vagina that will give vaginal discharge and itchiness.
- Trichomonas vaginalis can also be present in males in the urethra transmitted through sexual contacts. Other transmission of the Trichomonas protozoa can be by soiled towels, lavatory seats, sports clubs facilities and saunas .
- Coccidia and Giardia are two protozoans' that do invade and inhabit the lining of the small intestines in cats and dogs and create severe watery discharges or bloody diarrhoea .
- Equine protozoal myeloencephalitis is a condition that affects the nervous system of the equine, as it creates - 1 ⁇ inflammation of the brain tissue and damage to the spinal cord.
- the source of the parasite which creates this situation is Sarcocystis neurona normally derived from opossum faeces and this infective form is a "sporocyst" .
- the sporocyst is ingested by the horse from the grass it consumes and then the sporocyst enters the blood stream and enters the brain and forms lesions on the brain tissue and spinal cord.
- the equine When the equine is infected its coordination is erratic and has very little ability in moving its legs in a coordinated fashion.
- Acanthamoeba and Naegleria species are found worldwide and they are mainly in fresh water sources like lakes, rivers , hot springs and in hot tubs . They can be found in heating, venting and air conditioning units.
- Acanthamoeba infections of the eye can result in being transmitted through the use of soft contact lenses as well as the contact lens solutions not been clean and with this situation eye infections where the Acanthamoeba enters the eye through a cornea cut or sore and a corneal ulcer can result .
- Acanthamoeba can enter the skin through a cut, wound, or through the nostrils. Once inside they can travel to the lungs through the bloodstream and to other parts of the body, especially the nervous system. In the case of nervous system infections, these can be fatal.
- Naegleria entering the nasal passages of humans can cause a fatal situation.
- Tryanosoma the cause of the condition called African sleeping sickness and is conveyed by the Tsetse fly (Glossina) .
- the infection is developed in the blood stream which results in bouts of fever and malaise, a classical sleeping sickness syndrome.
- Toxoplasma protozoan is found in mainly felines in the intestinal system but upon transmission to humans can end up creating cogenital toxoplamosis (toxoplasma encephalitis) .
- Leishmania is widespread and produces zoonotic infections in dogs and rodents.
- Plasmodium With Plasmodium this is the protozoan parasite that induces Malaria in humans. This protozoan has four known species “vivax” , “malariae” , “ovale” and “falciparum” of which falciparum is the most common and deadliest species.
- the Plasmodium parasite is world wide and is transmitted by the Anopheles mosquito. When a human is infected from a mosquito bite the
- Plasmodium parasite enters the bloodstream and goes straight to the liver where it is safe and where it replicates itself many thousand times over within a two week period.
- the Plasmodium parasite requires Ferric and/or Ferrous ions to multiply so it attacks a plasma protein called "Transferrin" that transports Ferric/Ferrous ions through the blood to the liver, spleen and bone marrow.
- Brucella is an parasitic bacteria that causes Brucellosis in its various forms in sheep, goats, cattle, deer, elk, pigs, dogs and humans who come into contact with diseased animals. With humans brucellosis can cause a range of symptoms like, fevers, sweats, backaches, headaches and physical weakness . Transmission by humans is rare but lactating females can transmit the infection to their baby, and also it is reported that transmission by sexual activity has been recorded.
- compositions based on the use of chelating compounds as disclosed in WO 03/032944 are effective in the treatment of various parasite infestations for animals and humans in one or more different ways, further discussed herein below.
- compositions have the capability of killing nematodes over a period of time, allowing the animal to regain control over its digestive system and establish a healthy condition.
- compositions to be effective in the treatment of bot larvae infestations .
- compositions have the capability of entering the blood stream and attacking various Protozoan parasite and also Brucella present in the blood stream by chelating the Ferric and Ferrous ions .
- the chelate that has been formed denies the Ferric and Ferrous ions to the protozoan parasite and brucella.
- the chelate also actually enters the diseased cell and exerts a profound biological effect on it resulting in the death of the diseased cell .
- the present invention provides the use of a metal ion chelating agent for the manufacture of a medicament for the treatment or prophylaxis of a parasitic infestation, wherein the parasite is susceptible to coating by said metal ion chelating agent or being attacked by the chelate formed.
- the present invention provides the use of a metal ion chelating agent for the manufacture of a medicament for the treatment or prophylaxis of a parasitic infestation, wherein the parasite is nutritionally dependent on a host bacterial population and wherein said metal ion chelating agent has a metal ion chelating capacity for metal ions on which said host bacterial population is dependent for viability.
- the treatment or prophylaxis may be in respect of nematodes, and their bacterial food sources wherein said metal ion chelating agent provides a metal ion chelating capacity for at least one metal ion on which the said nematodes and their bacterial food sources are dependent for viability.
- the present invention provides the use of a metal ion chelating agent for the manufacture of a medicament for the treatment or prophylaxis of a parasitic infestation, wherein the parasite is susceptible to paralysis by said metal ion chelating agent .
- the present invention provides the use of a metal ion chelating agent for the manufacture of a medicament for the treatment or prophylaxis of a parasitic infestation, wherein the parasite is a bloodsucking or blood dependent parasite, and wherein said metal ion chelating agent has a metal ion chelating capacity for ferric and/or ferrous ions.
- the present invention provides the use of a metal ion chelating agent for the manufacture of a medicament for the treatment or prophylaxis of a nematode, cestode, bot larvae infestation or Protozoan parasite or Brucella infestation.
- This invention also provides a method for the treatment or prophylaxis, in a human or non-human, animal, of: a parasitic infestation, and especially of a parasitic infestation selected from a nematode, cestode and bot larvae, infestation, Protozoan and Brucella.
- the Protozoan's that may be present are Amoeba and flagellates, Trichomonas vaginalis, Acanthamoeba,
- Brucella may be present in animals as Brucella abortus, in seals as Brucella maris and in humans as Brucellosis.
- Treatment of animals for nematodes with the current treatments removes a proportion of the nematodes. After this treatment, a dose of active bacteria is required to achieve balance within the stomach and intestinal system to allow digestion of the food eaten.
- Nematodes and other parasitic organisms appear to have developed resistance to current treatments by blocking the effect of these treatments entering into their bodies; probably by coating themselves with a further resistant coating.
- the metal ion chelating composition appears to coat the nematodes and, at the same time, completely paralyse them so they cannot move or feed. In so doing it prevents the nematodes from eating all the digestive bacteria present .
- the nematodes After a period of time, with the nematodes unable to eat, they will die. The nematodes are in various stages of development within the stomach and intestinal system and they are all affected.
- the other mode of attack is that the metal ion chelating composition also coats the bacteria present and chelates the metal ions present that the bacteria relies on to survive. This means that, with the bacteria being coated or smothered and then starved to death, the food source for the nematodes has been eliminated and the nematodes will die.
- preferred chelating agents can chelate various different metal ions and thereby attack the nematodes by multiple, direct and indirect, routes. More particularly, it is preferable for the metal ion chelating agent to form a chelate with a plurality of metal ions selected from Mg 2+ , Fe 2+ , Cu 2+ , Zn 2+ , Mn 2+ , Ni 2+ , and Se 2+ . 8-hydroxyquinoline has been found to have a particularly broad spectrum of activity, chelating most metals apart from sodium, potassium and calcium.
- this metal ion chelating agent Upon treatment of equines with this metal ion chelating agent on a planned program dosage, no dead nematodes appear in their faeces for the first 3 days. The first dead nematodes and other parasites (such as bots) will then start to appear and will continue for typically another 6 days after which normally no more can be located in the dung. A great majority of the eggs are also emitted during that
- administration of a pro-biotic may be beneficial to assist the development of the natural bacteria population in the digestive system re-establishing itself.
- the metal ion and the metal ion chelating agent form together a stable complex such that the metal ion is effectively removed for a sufficient period of time to prejudice microbe viability and overcome the infection and/or to maintain a coating on the nematode, before the metal ion chelate dissociates.
- the metal ion and metal ion chelating agent should form a stable chelate under physiological conditions, and especially conditions prevailing in the intestinal tract where blood-sucking nematodes tend to be attached.
- the metal ion and the metal ion chelating agent form together a stable complex such that the metal ion is effectively removed or chelated to prejudice the viability of the Protozoan parasites and Brucella.
- the metal ion chelating agent is a heteropolar compound comprising at least one unsaturated heterocyclic six-membered ring in which at least one heteroatom moiety acts as a hydrogen acceptor and in which said compound also comprises at least one hydrogen donor moiety, conveniently a hydroxyl group, said heteropolar compound having no substituent which by itself or together with another substituent or substituents creates such steric hindrance and/or renders the molecule so basic or acidic or so alters the steric geometry of the molecule as to prevent interaction of the hydrogen donor and acceptor moieties of one molecule of heteropolar compound with the hydrogen donor and acceptor moieties of another molecule of said heteropolar compound.
- the preferred metal ion chelating agent is a hetero aryl compound having at least one nitrogen in the ring structure and at least one hydroxyl substituent disposed on the ring structure so as to provide together, a chelating function.
- Preferred metal ion chelating agents are selected from optionally substituted 2,3- dihydroxypyridine; 4 , 6-dihydroxypryrimidine; 2- pteridinol; 2 , 4-quinolindiol ; 2 , 3-dihydroxyquinoxalin; 2 , 4-pteridinediol ; 6-purinol; 3-phenanthridinol ; 2- phenanthrolinol ; 2-phenazinilol, and most preferred is 8- hydroxyquinoline .
- 8-hydroxyquinoline has the advantage of forming metal ion chelates with a particularly broad range of different metal ions.
- the present invention provides an orally ingestible pharmaceutical composition suitable for use in the treatment or prophylaxis of a parasitic infestation (such as a nematode, cestode, bot larvae infestation, protozoan parasites or brucella) , said composition comprising a physiologically acceptable metal ion chelating agent and a pharmaceutically acceptable carrier therefore, in which composition said metal ion chelating agent has at least one of: a metal ion chelating capacity for metal ions on which a host bacterial population providing nutrition to the parasite, is dependent for viability; a capability for coating the parasite; a capability for paralysing the parasite; and a metal ion chelating capacity for ferric and ferrous ions .
- a parasitic infestation such as a nematode, cestode, bot larvae infestation, protozoan parasites or brucella
- composition comprising a physiologically acceptable metal ion chelating agent and a pharmaceutically acceptable carrier therefore, in which
- compositions of the present invention for internal application will generally comprise from 0.000001% to 0.2% w/w, preferably from 0.00001 to 0.1, % w/w, conveniently from 0.0005 to 0.05 % w/w, of the chelating agent, depending on the particular administration route selected (e.g. admixed with dry feedstuff or drinking water, or administered as a liquid or paste-form drench etc) .
- a chelating agent concentration of around 0.05% w/w a convenient dosage of a liquid formulation suitable for incorporating into feed etc, would typically be around 10 mis.
- it is preferred to administer the composition directly to the animal then it is conveniently presented as a paste at a dosage of around 100 mis, using a chelating agent concentration of around 0.005% w/w.
- the dose rate of the liquid compound is according to their actual weight and may vary from about 5mls per day to about 20mls per day.
- the dose may vary from about 10mls at a time to about 20 mis at a time twice a day depending on the Protozoan parasite or Brucella and may be for a period of time from about 5-6 days to about 45-50 days.
- the period is typically for about 42 days dosing at the rate of about 20 mis per day.
- the period is typically for about 5 days dosing at the rate of about 20 mis per day.
- treatment may be for a period of about 5 days with a vagina flush and then application of the paste in the vagina .
- treatment of Trichomonas vaginalis in humans is typically for a period of about 5 days inserting the paste in the vagina or in the penis in the case of the male .
- Treatment of Acanthamoeba infections normally in the eye typically use about 10 mis of liquid compound per eye in a eyewash glass typically followed by application of about 5 mis of the paste around the eyelid for a period of about 5 days .
- Treatment of Equine Protozoal Myeloencephalitis is typically by adding about 50 mis per day to the equine feed and this treatment is for about 42-50 days.
- the doses and dose regimes used are readily determined by the skilled practitioner.
- orally ingestible composition may be used in accordance with the present invention.
- an aqueous based liquid composition which can be readily mixed in with dry feedstuff, incorporated in drinking water etc.
- a paste formulation or in encapsulated form e.g. using capsules of suitable material which are readily available, e.g. based on starch, gum and alginate.
- Suitable aqueous based compositions of 8-hydroxyquinoline can be prepared by using an intermediate solvent such as a polyolol, including glycols, preferably propylene glycol, glycerine, or sorbitol, and a wetting agent.
- an intermediate solvent such as a polyolol, including glycols, preferably propylene glycol, glycerine, or sorbitol, and a wetting agent.
- wetting agents are available that may be used which would give solubility of the metal ion chelating agent in glycol, including inter alia Polyoxyethylene Sorbitan Fatty Acid Ester T20, T40, T60 and T80 (Polysorbate) , and C9-C11 Alcohol ethoxylate (Symperonic 91/6,91/8) .
- a range of different proportions of the various components of the aqueous based compositions may be used depending on the solubilities of the metal ion chelating agents used, the final concentration required etc.
- the amount of wetting agent used is relatively sensitive.
- the intermediate solvent glycol etc
- the amount of this intermediate solvent can be readily increased further, though there is normally no particular advantage in doing so .
- a pH controller in order to ensure an alkaline pH in the composition, most preferably a pH in the region of 9.2 to 9.4.
- the pH controller may simply be KOH or NaOH.
- EDTA conveniently in the form of the DiSodium or TetraSodium salt .
- Deionised Water as required to obtain the final concentration required.
- pH controller as required to achieve a pH of 9.2 to 9.4.
- Example 2 Preparation of Veterinary Treatment Composition for nematodes and other parasites.
- the strength of this preparation is 125 ppm of 8- Hydroxyquinoline, whereby each millilitre contains 125 micrograms of the chelating agent.
- Estimated dosage rate of this composition for the following animals is as follows; a) Horses: 3.5 to 4.0 microgram per kg body weight for 9 days. This liquid can be put into their daily oats or hay that they consume .
- Sheep 3.5 to 4.0 micrograms per kg body weight for 6 days. This liquid can be placed in their daily feed.
- Dogs 3.0 to 4.0 micrograms per day/ estimated body weight for 5 days. This liquid can be placed in their daily food.
- the strength of this liquid preparation is 500 ppm of 8- hydroxquinoline, whereby each millilitre contains 500 micrograms of the chelating agent .
- the above liquid is taken and a 1.2 grams of thickener added being being either hydroxypropylcellulose of dehydoxanthan gum to produce 100 grams the paste with the desired viscosity.
- Trichomonas in towels etc. Place 50 mis of the Liquid compound per gallon of wash water in the washing machine to eliminate the presence of Trichomonas in soiled towels.
- Tetracycline The treatment with the liquid composition was for 6 weeks taking 10 mis in the morning, and 10 mis in the afternoon.
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Tropical Medicine & Parasitology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
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Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP06726749A EP1879576A1 (en) | 2005-04-14 | 2006-04-13 | Use of a metal ion chelating agent for the treatment of animal and human parasites |
AU2006235719A AU2006235719A1 (en) | 2005-04-14 | 2006-04-13 | Use of a metal ion chelating agent for the treatment of animal and human parasites |
JP2008505958A JP2008535901A (en) | 2005-04-14 | 2006-04-13 | Treatment of human and animal parasitic infections |
CA002606908A CA2606908A1 (en) | 2005-04-14 | 2006-04-13 | Use of a metal ion chelating agent for the treatment of animal and human parasites |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB0507490.1A GB0507490D0 (en) | 2005-04-14 | 2005-04-14 | Treatment of animal parasites |
GB0507490.1 | 2005-04-14 |
Publications (1)
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WO2006109069A1 true WO2006109069A1 (en) | 2006-10-19 |
Family
ID=34611081
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/GB2006/001350 WO2006109069A1 (en) | 2005-04-14 | 2006-04-13 | Use of a metal ion chelating agent for the treatment of animal and human parasites |
Country Status (6)
Country | Link |
---|---|
EP (1) | EP1879576A1 (en) |
JP (1) | JP2008535901A (en) |
AU (1) | AU2006235719A1 (en) |
CA (1) | CA2606908A1 (en) |
GB (1) | GB0507490D0 (en) |
WO (1) | WO2006109069A1 (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010013408A (en) * | 2008-07-04 | 2010-01-21 | Kanazawa Univ | Therapeutic or preventive medicine for protozoan diseases |
WO2015049546A1 (en) | 2013-10-04 | 2015-04-09 | Universitetet I Oslo | Inhibitors of metallo-beta-lactamase (mbl) comprising a zinc chelating moiety |
US9913824B2 (en) | 2010-01-25 | 2018-03-13 | Elanco Us Inc. | Methods for internally controlling or treating equine bot larvae |
US10961223B2 (en) | 2016-08-15 | 2021-03-30 | Universitetet I Oslo | Compounds |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016210780A (en) * | 2015-05-12 | 2016-12-15 | 参天製薬株式会社 | Administration of azole antifungal on palpebra skin |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3070498A (en) * | 1960-09-12 | 1962-12-25 | Wallace & Tiernan Inc | Nitrothiazole-hydroxyquinoline compositions |
AU3027984A (en) * | 1983-07-04 | 1985-01-10 | Australian National University, The | Antimalarial drugs |
US6407125B1 (en) * | 1995-12-29 | 2002-06-18 | Novactyl, Inc. | Pharmacological agent and method of treatment |
US20040248874A1 (en) * | 2001-10-12 | 2004-12-09 | Jemmett Alan Edwin | Anti-microbial composition comprising a metal ion chelating agent |
-
2005
- 2005-04-14 GB GBGB0507490.1A patent/GB0507490D0/en not_active Ceased
-
2006
- 2006-04-13 AU AU2006235719A patent/AU2006235719A1/en not_active Abandoned
- 2006-04-13 CA CA002606908A patent/CA2606908A1/en not_active Abandoned
- 2006-04-13 WO PCT/GB2006/001350 patent/WO2006109069A1/en not_active Application Discontinuation
- 2006-04-13 JP JP2008505958A patent/JP2008535901A/en active Pending
- 2006-04-13 EP EP06726749A patent/EP1879576A1/en not_active Withdrawn
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3070498A (en) * | 1960-09-12 | 1962-12-25 | Wallace & Tiernan Inc | Nitrothiazole-hydroxyquinoline compositions |
AU3027984A (en) * | 1983-07-04 | 1985-01-10 | Australian National University, The | Antimalarial drugs |
US6407125B1 (en) * | 1995-12-29 | 2002-06-18 | Novactyl, Inc. | Pharmacological agent and method of treatment |
US20040248874A1 (en) * | 2001-10-12 | 2004-12-09 | Jemmett Alan Edwin | Anti-microbial composition comprising a metal ion chelating agent |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010013408A (en) * | 2008-07-04 | 2010-01-21 | Kanazawa Univ | Therapeutic or preventive medicine for protozoan diseases |
US9913824B2 (en) | 2010-01-25 | 2018-03-13 | Elanco Us Inc. | Methods for internally controlling or treating equine bot larvae |
WO2015049546A1 (en) | 2013-10-04 | 2015-04-09 | Universitetet I Oslo | Inhibitors of metallo-beta-lactamase (mbl) comprising a zinc chelating moiety |
US10227327B2 (en) | 2013-10-04 | 2019-03-12 | Universitetet | Oslo | Inhibitors of metallo-beta-lactamase (MBL) comprising a zinc chelating moiety |
US10961223B2 (en) | 2016-08-15 | 2021-03-30 | Universitetet I Oslo | Compounds |
EP3978488A1 (en) | 2016-08-15 | 2022-04-06 | Universitetet I Oslo | Zinc chelating compounds for use in the treatment of bacterial infection |
US11649222B2 (en) | 2016-08-15 | 2023-05-16 | Universitetet I Oslo | Compounds |
Also Published As
Publication number | Publication date |
---|---|
CA2606908A1 (en) | 2006-10-19 |
AU2006235719A1 (en) | 2006-10-19 |
JP2008535901A (en) | 2008-09-04 |
GB0507490D0 (en) | 2005-05-18 |
EP1879576A1 (en) | 2008-01-23 |
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