Use of pharmaceutical compositions comprising thymol and/or carvacrol against histomoniasis

Abstract: The invention relates to pharmaceutical compositions comprising carvacrol and/or thymol as active agents as well as their use in the human and veterinary field. For instance, the compositions according to the invention can be used in the treatment of histomoniasis, an infectious disease of poultry, mainly of turkeys, in the treatment against hemoflagellates and in the treatment of inflammation diseases like pneumonia, nephritis, metritis, artritis, etc. Preferably the active agents are available in the form of an oil, extracted from a group of plants, like Origanum vulgaris, Thymus vulgaris and Mentha piperita

Description: Field of Invention The invention relates to the use of pharmaceutical compositions comprising carvacrol and/or thymol as active agents, for the preparation of a medicament against histomoniasis in poultry. More in particular histomoniasis is an infectious disease of poultry, mainly turkeys, due to Histomonas meleagridis with intestinal and hepatic lesions and dark discoloration of the comb ("black-head"). In detail the trophozoites of Histomonas meleagridis and resulting lesions are confined to the cecum and liver. The infected cecum is enlarged and the mucosa becomes necrotic consisting of leather-like cheesy material. The parasites lie singly or in small groups in the spaces between the cells. From the mucosa, they can spread to the submucosa and muscle layers and eventually be carried to the liver via the portal blood. The liver has circular areas or necrotic tissue usually resulting in impaired function. Early liver lesions are small in size, spherical and cream-colored while older lesions are large with depressed dark centers and a pale periphery. Clinical signs include drowsiness, weakness, and sulfur-colored droppings. Transmission can be by ingestion of trophozoites or ingestion of Heterakis gallinae (nematode) egg containing the trophozoite. In the latter case the flagellated form of the H.meleagridis is ingested by the co-habitating H.gallinarum nematode. The Histomonas passes through the gut wall of the female worm and penetrates into the ovary. It multiplies in the ovary and invades the oocysts. When embryonated Heterakis eggs are ingested by the susceptible host, the Histomonas escapes into the lumen of the cecum. Young birds usually have an acute form of the histomoniasis disease while older birds may appear sick for several days prior to becoming emaciated. Heaviest losses occur at 3 to 12 weeks of age. Many other species of birds including quail and pea fowl are also susceptible to above infection. A treatment is possible with nitroimidazole as well as the following medicines Dimetriazol and Ronidazol. Separation of species and ages is vital in preventing this disease. Problem related to the prior art Above-defined diseases are well known in the art, together with the relevant medications therefore. However, the prior art medications have been either forbidden on account of for example the presence of bioresidues in the meat of e.g. turkeys, its cancerogenic properties or they have become less active against the harmful microorganisms in question. Especially in the last decade many pathogenic microorganisms like Salmonella typhimurium DT 104 have build up considerable resistance to the marketed antibiotic products. Description of the solution of the above-described problem The primary component(s) to be used in the compositions according to the invention is thymol (2-hydroxy-1-isopropyl-4-methylbenzene) and/or carvacrol (2-hydroxy-4-isopropyl- 1 -methylbenzene). Although above active compounds may have a synthetic origin, preferably the active compounds are applied in the form of an oil extracted from any of the plants, selected from Origanum vulgaris, Thymus vulgaris, Mentha piperita, Thymus serpilum, Saturea hortensis, Saturea montana, Saturea subricata, Carum corticum, Thymus zugus, Ocimum gratisimum, Moranda pungtata, Mosla japanoica and Salvia officinalis. The pharmaceutical compositions according to the invention may comprise a pharmaceutically acceptable carrier, preferably of natural origin. Representatives of such carriers are generally known in the human and veterinary pharmaceutical field. Examples of such carriers are lactose, honey, laurel, vaselin, paraffin, starch products, calcium carbonate, etc. The pharmaceutical compositions may have any form suitable for its application, for instance the form of a water-soluble solution and a powder in the case of the treatment of histomoniasis and in the form of an injectable solution in the case of the above-defined inflammations. The content of active agent in the pharmaceutical compositions according to the invention, which in fact does also depend on its pharmaceutical use, may vary between wide limits. Preferably the active agent in the form of thymol and/or carvacrol is present in an amount of 1-10% by weight, most preferably 2-5 % by weight, calculated on the total weight of the pharmaceutical composition. Further to the active agent according to the invention also other active substances, preferably of natural origin, can be used. Such substances may have bacteriological, fungicidal, adstrigidic etc. properties. The way of application of the pharmaceutical compositions according to the invention depends on their form. For instance, the treatment of histomoniasis may be carried out by means of a water soluble solution or powder per oral. Examples of forms of pharmaceutical compositions to be used according to the invention are for instance: 1) Powder form The following composition in powder form may be used in the treatment of poultry, e.g. turkeys, against histomoniasis. CaCO 3 20-25 wt.% Magnesium stearate 3-5 wt. % Potato starch 25-30 wt. % Dextrose 45-50 wt. % Carvacrol or Thymol 3-4 wt. % 2) Water soluble solution The following composition may be used in the treatment of poultry against histomoniasis. Double distilled water 4-5 wt. % Polysorbate 60-65 wt. % Monoethylene glycol 30-35 wt. % Carvacrol and/or Thymol 3-4 wt. % Example 1 The following powder composition was applied: CaCO 3 25 wt. % Magnesium stearate 5 wt. % Potato starch 25 wt. % Dextrose 41 wt. % Carvacrol and/or Thymol 4 wt. % In a farm 90 turkeys, suffering from both histomoniasis and rhinitis were treated with the above-defined composition in a dosis of 5 g/kg over 10 days. At the first day of the treatment only one turkey died. The others recreated quickly, and only some of them still had rhinitis. For comparison purposes 90 turkeys of the same group as above, also suffering from both histomoniasis and rhinitis, were treated by the marketed product "Bayril". However, 20 turkeys died without showing sulfur-coloured feces before. At necropsy of four of these turkeys , they showed the typical picture of typhlohepatitis in different degrees of severity.

Claims: Use of a composition comprising carvacrol and/or thymol for the manufacture of a medicament for therapeutic prevention or treatment of histomoniasis in poultry. Use according to claim 1, characterized in that the active agent is thymol and/or carvacrol as present in the oil, extracted from any of the plants selected from Origanum vulgaris, Thymus vulgaris, Mentha piperita, Thymus serpilum, Saturea hortensis, Saturea montana, Saturea subricata, Carum corticum, Thymus zugis, Ocimum gratisimum, Moranda pungtata, Mosla japanoica and Salvia officinalis. Use according to any of claim 1-2, characterized in that the active agent is at least an oil, extracted from any of the plants, selected from Origanum vulgaris, Thymus vulgaris and Mentha piperita. Use according to claim 3, characterized in that the active agent is at least an oil extracted from Origanum vulgaris and optionally Thymus vulgaris. Use according to any of claims 1-4, characterized in that the pharmaceutical carrier is of a natural origin. Use according to claim 5, characterized in that the pharmaceutical carrier is selected from lactose, honey, laurel, vaselin, paraffin, starch products and calcium carbonate. Use according to any of the claims 1-6, characterized in that the active agent in the form of thymol and/or carvacrol is present in an amount of 1-10% by weight, calculated on the total weight of the composition. Use according to claim 7, characterized in that the active agent is present in an amount of 2-5% by weight, calculated on the total weight of the composition. Use according to any of the claims 1-8, characterized in that the medicament has the form of a water-soluble solution or a powder. Use according to any of the claims 1-8, characterized in that the medicament has the form of an injectable solution.

Inventors: NINKOV DUSAN, NINKOV, DUSAN, NINKOV, DUSAN ROPAPHARM B.V.
Applicants: ROPAPHARM B V, ROPAPHARM B.V.
Application year: 1997
Main classification: A61K31
IPC codes: A61K31