NZ243613A

NZ243613A - Tablet comprising praziquantel, pyrantel pamoate and oxantel pamoate in synergistic proportions for treatment of nematode infestations

Info

Publication number: NZ243613A
Application number: NZ24361392A
Authority: NZ
Inventors: Donald George Mclaren; Wayne Frederick Leech
Original assignee: Bomac Lab Ltd
Priority date: 1992-07-17
Filing date: 1992-07-17
Publication date: 1996-04-26

Description

<div class="application article clearfix" id="description"> New Zealand Paient Spedficaiion for Paient Number £43613 2436 13 NEW ZEALAND PATENTS ACT. 1953 No.: 243613 Date: 17 July 1992 COMPLETE SPECIFICATION "Improvements in or Relating to Anthelmintic Compositions and/or Methods of Treating Non-Human Mammals" We, BOMAC LABORATORIES LIMITED, a company duly incorporated under the laws of New Zealand of Cnr Win Station Road and Hobill Avenue, Manukau City, Auckland, New Zealand hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- 24 3 6 1 3 This invention relates to anthelmintics and to methods of treatment of animals with anthelmintics. Praziquantel is a known efficient specific cesticodal drug active against common tape worms of dogs and cats and also known as active against larval cestodes and cestodes of ruminants. Pyrantel and its meta-axyphenyl analogue oxantel are known anthelmintics having high efficacy against roundworms and hookworms. The combination of oxantel and pyrantel is known to have a broader spectrum efficacy than pyrantel alone. A disadvantage of known anthelmintic treatments for animals has been the relatively specific action of the common drugs used, and occasional occurrences of resistance to particular drugs by certain organisms, resulting in continued infection by one or more parasites after treatment It has now been found unexpectedly that an anthelmintic composition combining praziquantel, pyrantel pamoate and oxantel pamoate goes at least some way to overcoming these disadvantages and is believed to be of greater efficacy and stability than would be expected from a consideration of data for the individual active ingredients, and also produces an adequately shelf stable composition with low toxicity. Also described is a method of treating non-human mammals with anthelmintic compounds which goes at least some way to overcoming the abovementioned disadvantages and/or which will at least provide the public with a useful choice. Accordingly, in a first aspect, the invention may broadly be said to consist in an anthelmintic composition comprising a synergistic mixture of praziquantel, oxantel pamoate, and pyrantel pamoate. The finished composition in the preferred form may comprise from substantially 2 to substantially 20% w/w praziquantel, from substantially 5 to substantially 50% w/w 2436 13 pyrantel pamoate, and from substantially 20 to substantially 90% w/w oxantel pamoate. More preferably, said composition comprises from substantially 5 to substantially 6% w/w praziquantel, from substantially 13 to substantially 16% w/w pyrantel pamoate and from substantially 50 to substantially 62% w/w oxantel pamoate, and is in the form of a shelf stable tablet, liquid, or paste. The composition may include disintegrating, bulking and/or lubricating agents. In a second aspect, the invention consists in a method of treating gastrointestinal parasites in non-human mammals comprising the simultaneous administration to said non-human mammal of praziquantel, oxantel pamoate and pyrantel pamoate in biologically acceptable concentrations. To those skilled in the art to which the invention relates, many changes in construction and widely differing embodiments and applications of the invention will suggest themselves without departing from the scope of the invention as defined in the appended chims. The disclosures and the descriptions herein are purely illustrative and are not intended to be in any sense limiting. The invention consists in the foregoing and also envisages compositions and methods of which the following gives examples. The preferred method of preparing the composition according to the invention will now be described, together with the preferred formulation for the finished composition and/or for a composition suitable for use in carrying out the method of the invention. Praziquantel, having the formula: 2-cyclohexyl carbonyl-1, 3, 4, 6, 7, llb-hexahydro-2H pyrazino (2, la) isoquinolin- 4 one l-msthyl-l, 4, 5, 6-tetrahydro-2-[2-(3-hydroxyphenyl)vinyl] pyrimidine , and pyrantel pamoate being the pamoate sale of pyrantel having the formula: 1, 4, 5, 6-tetrahydro-l-methyl-2-(2-thienyl) vinyl pyrimidine H , together with lactose, all being in dry powder form, are passed through a 100-mesh screen and mixed. A suitable disintegrating agent, such as crospovidone (cross-linked insoluble polyvinylpyrrolidone), is dispersed in sufficient deionised water and added to the mixture of dry powders, the resulting mixture then being further mixed to form granules. ' 2436 13 The granules are dried to a suitable consistency and dry screened. Suitable binding and lubricating agents such as sodium starch glycolate (primogel), microcrystalline cellulose (avicel PH101), and magnesium stearate are passed through a suitable screen such as a 100-mesh screen and mixed with the granules prepared above, for five minutes. The total mixture is then formed into tablets. For example in one presently preferred form of the invention the finished product comprises a 970mg tablet which contains substantially 45.0-55.0nig praziquantel, substantially 126-154mg pyrantel pamoate and substantially 490-600mg oxantel pamoate, meeting approved standards of hardness, disintegration, weight variation and stability, and is so formulated as to disintegrate in the stomach of the recipient animal Preferably, the finished composition comprises a 970mg tablet comprising substantially 50mg praziquantel, substantially 545mg oxantel pamoate and substantially 140mg pyrantel pamoate. An example of the preferred exact formulation is given below: Praziquantel 5.1546% w/w Oxantel Pamoate 56.1856% Pyrantel Pamoate 14.4330% Lactose 16.6804% Crospovidone 2.0000% Primogel 1.5464% Avicel pHlOl 3.0000% Magnesium Stearate 1.0000% Deionised Water (for granulation) qs Total 100% 2436 13 The composition of the invention may also be formulated as for example a liquid or a paste. In carrying out the method according to the invention, praziquantel, oxantel pamoate and pyrantel pamoate are simultaneously administered to a non-human mammal. A suitable means of administering the compounds will be by way of a composition such as that described above comprising the three named compounds. This may for example be in the form of a solid tablet as described above or may be in another form for example as a liquid or paste which may be administered to the animal. The composition according to the invention has been tested on dogs and cats under veterinary supervision at twice the recommended dose rate (one tablet to five kilogram body weight) by ingestion of tablets. None of the animals dosed displayed any signs of toxicity or adverse effects during the observation period. It is found that the composition of the invention and/or the method of treatment of the invention is particularly useful in treatment of animals in particular dogs infected with gastro intestinal parasites including tapeworms, hookworms and other worm parasites. The efficacy of the three active compounds is not found to be diminished by being administered simultaneously and indeed the simultaneous administration of the three compounds appears to have an unexpectedly synergistic effect giving a very high broad spectrum activity against a wide range of parasites. It is believed that the composition and/or the simultaneous administration method of the invention demonstrates unexpectedly high efficacy against parasites of demonstrated resistance to known single agent or combination anthelmintics. </div>

Claims

<div class="application article clearfix printTableText" id="claims"> O " ' "7 /T^ Jt ^ J 0 1 Furthermore, the very high broad spectrum efficacy of the composition reduces the likelihood of any survival of parasites, and therefore substantially reduces the development of resistant parasite 'trains. It is believed that the composition of the invention demonstrates this synergistic mode of action through highly beneficial effects on the recipient animals which demonstrate increased rates of growth and enhanced thrift Not wishing to be bound by any theory, it is hypothesised that simultaneous administration of praziquantel, pyrantel pamoate and oxantel pamoate results in prolonged blood levels of these compounds as compared with any one of these compounds alone, possibly as a result of a synergistic blocking or delaying effect on the breakdown or excretory routes. While combinations of oxantel and pyrantel have previously been known and marketed, it has not before been suggested that combining these two compounds with praziquantel would be particularly effective or would produce a compound having adequate shelf stability. The present composition is believed to be adequately shelf stable for at least substantially 18 months. Thus it can be seen that an anthelmintic composition and a method of treating non-human mammals with anthelmintics is provided by the invention which is unexpectedly effective and stable and provides a significant advance over existing compositions and methods of treatment 243613 WHAT WE CLAIM IS:

1. A synergistic anthelmintic composition suitable for administration to mammals to treat disease complex of parasitism, said composition comprising synergistically effective amounts of praziquantel, oxantel pamoate, and pyrantel pamoate in a pharmaceutically acceptable dosage form.

2. A composition as claimed in claim 1 comprising from substantially 2 to substantially 20% w/w praziquantel, from substantially 5 to substantially 50% w/w pyrantel pamoate, and from substantially 20 to substantially 90% w/w oxantel pamoate.

3. A composition as claimed in claim 2 comprising from substantially 5 to substantially 6% w/w praziquantel, from substantially 13 to substantially 16% w/w pyrantel pamoate and from substantially 50 to substantially 62% w/w oxantel pamoate.

4. A composition as claimed in any one of claims 1 to 3 in the form of a shelf stable tablet, liquid, or paste.

5. A composition as claimed in any one of claims 1 to 4 including in addition disintegrating, bulking and/or lubricating agents.

6. A composition as claimed in any one of the preceding claims substantially as hereinbefore described with reference to the example.

7. A method of treating gastro-intestmal parasites in non-human mammals comprising the simultaneous administration to said non-human mammal of praziquantel, oxantel pamoate and pyrantel pamoate in biologically acceptable concentrations and in synergistically effective amounts.

8. A method of treating gastro-intestinal parasites in non-human mammals comprising the oral administration of an anthelmintic composition as claimed in any one of claims 1 to 6. DATED THIS hf </div>