New therapeutic use of Fagaricine as a drug to treat stenoxenic hemoprotozoal infections in tropical countries

Abstract

The present invention relates to a new therapeutic use of Fagaricine as an orally administered drug for the treatment of stenoxenous hemoprotozoal infections in tropical countries. Fagaricine, containing as its active ingredient an extract of Zanthoxylum heitzii, can be combined with the extract of at least one of the following plants: Carapa procera, Vernonia amygdalina, Alstonia boonei, Alstonia congensis, Combretum micranthum, Crossopteryx febrifuga, Enantia chlorantha, Eucalyptus globulus, Harungana madagascariensis, Lophira alata, Picralima nitida, Piper umbellatum, Tricoscypha ferruginea, Voacanga africana, Artemisia annua, Artemisia afra.

Description

Title of the invention: New therapeutic use of Fa-garicine as a drug for treating stenoxene hemoprotozoa in tropical countries.

[0001] The present invention relates to a new therapeutic use of Fa-garicine and its active ingredient, the aqueous extract of Zanthoxylum heitzii, as a medicament administered orally to treat stenoxene hemoprotozoa in tropical countries.

[0002] Some definitions

[0003] To better understand this text it is desirable to define some of the words and terms used in it. The majority of all the terms and terms used are defined in the Illustrated Dictionary of Medical Terms by Garnier Delamare, 28th edition.

[0004] Excipient: It is a vehicle for a drug. It is a substance into which the active ingredients are incorporated to make them easily absorbable.

[0005] Nutrients: food substance that can be directly and completely assimilated, without having to undergo the changes of digestion and that can be introduced by intravenous injection. Example: glucose, vitamins, mineral salts etc.

[0006] Medicine: Substance or combination of substances presented as having curative or preventive properties with regard to human or animal diseases, as well as any product which can be administered to humans or animals with a view to establishing a medical diagnosis, restoring, correcting or modifying their organic functions.

[0007] Essential medicine: A medicine that meets the priority health care needs of the population. These medicines are generally used for priority conditions and are included on the national list of essential medicines.

[0008] Aqueous extract: We mean by aqueous extract, the extract using as solvent only water in liquid or vapor form.

[0009] Protozoa: Disease caused by protozoa.

[0010] Protozoa: Subkingdom of unicellular animals including rhizopods, flagellates, sporozoa and infusoria.

[0011] Haemoprotozoosis: synonym for blood protozoosis. Generic name for diseases caused by the presence in the blood of parasites belonging to the protozoa branch; malaria, trypanosomiasis, leishmaniasis, piroplasmosis, anaplasmosis.

[0012] Per os: orally

[0013] Stenoxena: in biology, said of a parasite having only one definitive host. Stenoxena parasites (lice, hematozoa) are adapted, dependent on a single host; Euryxenes, on the contrary, only present a loose specificity: this is the case of the agents of zoonoses, parasitoses common to humans and animals - toxoplasmosis, distomatoses, larval forms of tapeworms (hydatidosis, alveolar echinococcosis).

[0014] According to the guidelines of the European Patent Office, therapy involves the cure of a disease or organic dysfunction and includes prophylactic treatments such as, for example, immunization against a certain disease or the removal of dental plaque. A method for therapeutic purposes, which relates to the operation of an apparatus in contact with a living human or animal body, is not excluded from patentability if there is no functional relationship between the operations related to the use of the apparatus and the therapeutic effect exerted on the body by it.

[0015] The present invention relates to a new therapeutic use of the aqueous extract of the bark of Zanthoxylum heitzii (active principle of Fagaricine) combined with the aqueous extract of at least one of the plants from list 1 of the following: Carapa procera, Vernonia amygdalina, Alstonia boonei, Alstonia congensis, Combretum mi-cranthum, Crossopteryx febrifuga, Enantia chlorantha, Eucalyptus globulus, Harungana madagascariensis, Lophira alata, Picralima nitida, Piper umbellatum, Tri-coscypha ferruginea, Voacanga africana, Artemisia afra, Artemisia annua administered orally (per os) to treat stenoxene hemoprotozoa in humans in tropical countries.

[0016] The aqueous extract of Zanthoxylum heitzii, also called Fagara heitzii, is the active ingredient of Fagaricin (F-532), a drug used as an immunoreconstituent to strengthen the immune defenses of immunocompromised people. This phytomedicine has been authorized since 2005 and is sold in several countries, particularly in sub-Saharan Africa. Fagaricin as a drug has been protected for its antiviral and antibacterial properties and for stimulating immune defenses (PCT WO 2005 / 021019 Al). List 1

[0017] Carapa procera, Vernonia amygdalina, Alstonia boonei, Alstonia congensis, Combretum micranthum, Crossopteryx febrifuga, Enantia chlorantha, Eucalyptus globulus, Harungana madagascariensis, Lophira alata, Picralima nitida, Piper umbellatum, Tricoscypha ferruginea, Voacanga africana, Artemisia afra, Artemisia annua.

[0018] The present invention relates to a new therapeutic use of Fagaricin (F-532) or its active ingredient which is the aqueous extract of the bark of Zanthoxylum heitzii: combined with the aqueous extract of at least one of the plants from the following list 1: Carapa procera, Vernonia amygdalina, Alstonia boonei, Alstonia congensis, Combretum micranthum, Crossopteryx febrifuga, Enantia chlorantha, Eucalyptus globulus, Harungana madagascariensis, Lophira alata, Picralima nitida, Piper um- bellatum, Tricoscypha ferruginea, Voacanga africana, Artemisia annua, Artemisia afra, administered orally (per os) to treat stenoxenous hemoprotozoa in humans in tropical countries.

[0019] According to the guidelines of the European Patent Office, where a substance or composition is already known, (theoretical) novelty may arise from a new medical use pursuant to Article 54(4) and (5).

[0020] According to Article 54(4), even if a substance or composition is known, it may be patented for the performance of a method referred to in Article 53(c) if its use has not been previously disclosed for such a method (first medical use). A claim to a known substance or composition that would be used for the first time in a surgical, therapeutic and / or diagnostic method must be formulated as follows: -Substance or composition X, followed by the indication of the use, e.g., for use as a medicament or - for use for in vivo therapeutic / diagnostic / surgical purposes.

[0021] Furthermore, if the use of the known substance or composition has already been disclosed in surgery, therapy or for diagnostic methods applied to the human or animal body, a patent may still be obtained under Article 54(5) for a second or subsequent medical use of that substance in one of those methods provided that said use is new and inventive (subsequent medical use). A claim for a subsequent medical use of a known substance should be formulated as follows: "Substance or composition X", followed by the indication of the specific use for therapeutic / in vivo diagnostic / surgical purposes, e.g., -for use in the treatment of disease Y.

[0022] It is for this reason that the applicant wishes to patent the following composition:

[0023] Fagaricin (F-532) containing as an active principle the aqueous extract of the bark of Zanthoxylum heitzii associated with the aqueous extract of at least one of the following plants: Carapa procera, Vernonia amygdalina, Alstonia boonei, Alstonia congensis, Combretum micranthum, Crossopteryx febrifuga, Enantia chlorantha, Eucalyptus, globushiras, Habulus, Habuluphirangana Picralima nitida, Piper um-bellatum, Tricoscypha ferruginea, Voacanga africana, Artemisia annua, Artemisia afra, for its use as an orally administered drug to treat stenoxen Hemoprotozoa of tropical countries.

[0024] Preferably, the aqueous extract according to the invention contains between 1% and 99% by weight of the extract of Zanthoxylum heitzii relative to the total weight of the composition or of the medicament and between 0.1% to 80% by weight of the aqueous extract of at least one of the plants of list 1 relative to the total weight of the composition or of the medicament.

[0025] According to the invention, the various pharmaceutical compositions containing Zanthoxylum heitzii and at least one of the plants in list 1 are called Zanthoxylum-based combination therapy (ZCT). When Zanthoxylum heitzii is used only with Artemisia annua, or Artemisia afra the pharmaceutical composition is called Artemisia-based combination therapy (ACT).

[0026] Dosage forms

[0027] According to the invention, the composition can be presented in the form of tablets, capsules, granules, syrup, oral solution or any other forms known to those skilled in the art comprising lavender extract or mixed with at least one aqueous plant extract from list 1.

[0028] Those skilled in the art know and use various excipients as binders or lubricants for manufacturing powders, granules or other preparations. Examples of excipients which can thus be used according to the invention are: lactose, starch, dextrin, calcium phosphate, calcium carbonate, natural or synthetic aluminum silicate, magnesium oxide, hydrated aluminum hydroxide, magnesium stearate, sodium bicarbonate, rice starch. Other excipients not mentioned above but which are also suitable are described in “Remington's Pharmaceutical Sciences” by EW Martin, and can be used according to the invention.

[0029] In these different formulations, and for example those mentioned above, the composition can also be presented in powder for dilution or syrup. This powder may contain only the active ingredients. This is obtained for example by atomization, drying, or lyophilization from the aqueous, hydroalcoholic extract. The aim of the invention is therefore to propose a new pharmaceutical and / or dietary composition as an anticancer or as an antimitotic to combat the divisions of human, animal or plant cells.

[0030] The applicant achieves that the administration of an effective quantity of the mixture of an aqueous extract of Zanthoxylum heitzii associated with at least one of the plants from the plants of list 1 and administered orally to treat human stenoxenic hemoprotozooses in tropical countries. Technical field of the invention

[0031] The implementation of the invention can be done on the activity of Fagaricine alone 200 mg or associated with the aqueous extract of Artemisia annua 255 mg, or Artemisia afra. 255 mg, on the destruction of Hemoprotozooses.

[0032] Activity of Fagaricin alone or associated with Artemisia annus on Haemoprotozooses.

[0033] A biological test based on the demonstration of the elimination of hematozoa in human blood see species determination.

[0034] Protocol for demonstrating the activity of the invention Parasitological diagnosis:

[0035] This is the discovery of the hematozoan. The blood sample is taken as close as possible to the thermal access. It consists of collecting 1 or 2 drops of blood after pricking the finger, the earlobe or, in children, the heel. In practice, it is often preferable for a non-specialist doctor to send blood taken by venipuncture on an anticoagulant to the laboratory.

[0036] The search for the parasite is carried out on thin smears. Thin smears must be very carefully prepared to give truly single-cell spreads. They will be stained by the May Grünwald Giemsa method which stains the cytoplasm blue and the nucleus red. The result can be obtained urgently. The thick drop is a technique which makes it possible to highlight parasites when they are relatively rare, in a larger quantity of blood, and will be stained by the Giemsa method. The few hours of drying necessary for its preparation do not allow it to be interpreted urgently. Results

[0037] The method of identifying parasites in the blood allows not only to make the diagnosis, but also to verify the effectiveness of the treatment administered.

[0038] [Fig.l] represents the effectiveness of Fagaricine or F-532 according to the invention and Fa-garicine associated with Artemisia annua as V Artemisia afra according to the invention on parasitaemia (hematozoan).

[0039] According to the invention, the composition can be used as: 1) Fagaricine containing as active ingredient the aqueous extract of the bark of Zanthoxylum heitzii, for its use as a medicament to be administered orally to treat stenoxene hemoprotozooses in tropical countries. 2) Fagaricine containing as active ingredient the aqueous extract of the bark of Zanthoxylum heitzii combined with the aqueous extract of at least one of the following plants: Carapa procera, Vemonia amygdalina, Alstonia boonei, Alstonia congensis, Combretum micranthum, Crossopteryx febrifuga, Enantia chlorantha, Eucalyptus globulus, Harungana madagascariensis, Lophira alata, Picralima nitida, Piper umbellatum, Tricoscypha ferruginea, Voacanga africana, for its use as an antimalarial drug called Zanthoxylum-based combination therapy, abbreviated to ZCT.3) Fagaricine containing as active ingredient the aqueous extract of the bark of Zanthoxylum heitzii, combined with the aqueous extract of at least one of the following plants: Artemisia annua, Artemisia afra, for its use as an antimalarial drug called Artemisia-based combination therapy, abbreviated ACT. 4) Pharmaceutical composition for treating Hemoprotozoa. containing Fagaricin and an associated aqueous extract of the plant representing between 0.1% and 80% by weight relative to the total weight of said composition.

Claims

Claims

1. Association of Fagaricine or an aqueous extract of Zanthoxylum heitzii, with an aqueous extract of at least one of the following plants: Artemisia annua, Artemisia afra, for its use as an antimalarial drug called Artemisia-based combination therapy abbreviated to ACT, said association being in a form suitable for oral administration.

2. Composition for antimalarial drug, comprising the combination of Fagaricin or an aqueous extract of Zanthoxylum heitzii, with an aqueous extract of at least one of the following plants: Artemisia annua, Artemisia afra, characterized in that the aqueous extract of the plant combined with Fagaricin represents between 0.1% and 80% by weight relative to the total weight of said composition.

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