WO2000078149A1 - Anthelmintic compositions - Google Patents

Abstract

The invention relates to an anthelmintic composition comprising praziquantel, and polyethylene glycol, production thereof and use of said compositions for combating endoparasites.

Description

  
 



  The composition may, for example, include levamisole, salts thereof or other derivatives thereof. Thus, the levamisole may be levamisole either as a base or as a hydrohalogen salt (e. g. the hydrochloride salt) or as a phosphate salt as a supplementary active   ingredient.    The levamisole may render the composition effective against roundworms as well.



  Other active ingredients such as niclosamide, and/or closantel, and/or oxyclozanide may also be included.



  The composition may also include other customary   formulating    agents.



  The composition of the present invention may be used as an anthelmintic for veterinary or human use. It may be administered orally or as a liquid in a capsule or in the form of a granulate or tablet made by using the aforementioned solution.



  The composition is manufactured by mixing the suitable amount of components in an apparatus usually suitable for that purpose.



  In a preferred embodiment of the invention the composition is administered at a rate of 2.5 mg/kg or above   (praziquantel/body    means of the person or animal administered to). Preferably it is administered at a rate of 3.75   mg/kg.    These dosage rates are particularly suitable for sheep.



  The invention will now be further illustrated by way of example without thereby limiting the scope of the invention.  



  Example 1
Polyethylene glycol solution of praziquantel 2.5 g praziquantel was added to 100 g polyethylene glycol and dissolved by   stirring.   



  In this way a 2.5% praziquantel solution was formed.



  Example 2
Efficacy evaluation of oral formulations of praziquantel against a confirme natural infestation of Moniezia expansa in lambs.



  The efficacy of a 2.5% praziquantel solution according to the invention, prepared as described in Example 1 ("The Test Article"), was tested at various dosage rates against a commercially available praziquantel formulation (Cestocur) made up as a suspension ("The Standard") for the control of Moniezia expansa. The Standard was administered at the prescribed dosage rate of 5 mg/kg that is 5 mg praziquantel per kg body mass of the animal.



  Examination of the ingesta and staining and identification of the Moniezia expansa was done in the laboratory. Dorper lambs of approximately two months of age were utilise during the trial. The lambs were housed in a kraal for the duration of the trial and fed lucerne with water available on tap.



  The cestocides were tested in naturally infested lambs which was confirmed on the trial premises. Moniezia expansa is readily diagnosed in the live animal. Diagnosis was done using egg morphology and   excreted    strobilae although these may be digested with corresponding difficulty of identification. The trial was done on the lines of a staggered critical control test.



  The animals were divided in groups and within each of the groups, and on three consecutive days, some animals were treated with the Test Article (various dosage  rates) some with the Standard (prescribed dosage rate of 5 mg/kg) and some were untreated controls ("The Controls") for comparison.



  The animals involved in each stagger were equipped with faecal collection bags for one day pre-treatment and three days post-treatment. The faeces thus collected were examined for the presence of strobilae.



  The animals involved in each stagger were slaughtered four days post-treatment following the procedure hereunder: 1. Animals were euthanased, skinned and the abdominal cavity opened. The
 gastro-intestinal tract was removed and from this the small intestine and
 caecum/colon was recovered. These were labelled with the animal's number.



  2. Intestines were placed in a bucket. Water was added to both ends of the
 intestine allowing filling at each end to approximately 1-2 meters.



  3. The water was allowed to flow through the intestine from both ends until a
 loop was formed at the bottom end located in the bucket.



  4. One end of the intestine was released and the water was forced from the
 intestine by sliding the organ gently between the fingers.



  5. The organ was then opened along its entire length using a pair of bowel
 scissors after which the wall was thoroughly washed under a stream of water.
 The intestine was then sealed in a glass jar after the addition of   formalin    for
 preservation. This was done in case later examination might be required.



  6. Ingesta was recovered, sluiced through an Endecotts sieve and stored in glass
 jars for examination in the laboratory under direct sunlight in the plastic pans.  



  The results were as follows:
EMI5.1     


Number <SEP> of <SEP> Animals <SEP> Remedy <SEP> Dose <SEP> Rate* <SEP> Animals <SEP> infested <SEP> at <SEP> Post <SEP> Mortem <SEP> 1
<tb>  <SEP> 7 <SEP> Test <SEP> Article <SEP> 1. <SEP> 25 <SEP> mg/kg <SEP> 6
<tb>  <SEP> 7 <SEP> Test <SEP> Article <SEP> 1. <SEP> 25 <SEP> mg/kg <SEP> 0
<tb> 
EMI5.2     


<tb> Number <SEP> of <SEP> DoseRate*AnimalsRemedy <SEP> infested <SEP> at <SEP> Post <SEP> Mortem
<tb>  <SEP> Article3.75mg/kg06Test <SEP> 
<tb>  <SEP> 7 <SEP> Test <SEP> Article <SEP> 5 <SEP> mg/kg <SEP> 0
<tb>  <SEP> 9 <SEP> Standard <SEP> 5 <SEP> mg/kg <SEP> 0
<tb>  <SEP> 6 <SEP> Control--6
<tb>  * The dosage rate is expressed as mg praziquantel per kg body mass of the animal.



  The results indicate that the Test Article is as effective as the Standard at a dosage rate as low as 2.5 mg/kg compared to the dosage rate of 5 mg/kg of the Standard. A dosage rate of 3.75 mg/kg provides consistent control and is preferred for sheep.



  It will be appreciated that when customary praziquantel suspensions are prepared, great care has to be taken to ensure that the correct particle size of the praziquantel is obtained. Additives to maintain the suspension and preserve the product are also required which adds to the costs of the product. The present invention does not require such excipients and is   self-preserving.   



  The present invention is also much easier to prepare.



   It will further be appreciated that many variations in details are possible   without   
 thereby departing from the scope and spirit of the invention.
  

Claims

Anthelmintic Compositions This invention relates to an anthelmintic composition. More particularly it relates to an anthelmintic composition containing praziquantel as an active ingredient.

Praziquantel (2- (cyclohexylcarbonyl)-1,2,3,6,7,1lb-hexahydro-4H-pyrazino [2,1a] isoquinolin-4-one) is a known anthelmintic composition sold by Bayer (Pty) Ltd. under the trade name Cestocur. Known compositions of praziquantel comprise a suspension of praziquantel in a liquid medium. These suspensions are conventionally administered to animals, particularly sheep at a dosage rate of 5 mg praziquantel per kilogram body mass for the control of cestode and/or conical fluke infestations.

Surprisingly, it has now been found that effective control of cestode and/or conical fluke infestation can be achieved with praziquantel at seemingly reduced dosage rates if the praziquantel is administered in a composition according to the present invention.

According to the present invention an anthelmintic composition comprises praziquantel or a pharmaceutically acceptable salt or a derivative thereof dissolved in polyethylene glycol.

Preferably praziquantel is dissolved in the polyethylene glycol.

The solution may comprise from 1% to about 6% mass praziquantel per mass polyethylene glycol. In one preferred embodiment of the invention the solution comprises 2.5% praziquantel per polyethylene glycol (mass/mass).

The composition may also include one or more other active ingredients. Such active ingredients may be aimed at extending the therapeutic spectrum of the formulation.

The one or more other active ingredients may be present in the form of a suspension and/or a solution.