WO2006061214A1 - Anthelmintic composition - Google Patents

Anthelmintic composition Download PDF

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Publication number
WO2006061214A1
WO2006061214A1 PCT/EP2005/013139 EP2005013139W WO2006061214A1 WO 2006061214 A1 WO2006061214 A1 WO 2006061214A1 EP 2005013139 W EP2005013139 W EP 2005013139W WO 2006061214 A1 WO2006061214 A1 WO 2006061214A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
anthelmintic
praziquantel
anthelmintic composition
oxyclosanide
Prior art date
Application number
PCT/EP2005/013139
Other languages
French (fr)
Inventor
Ernest Schay
Original Assignee
Bayer Healthcare Ag
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Bayer Healthcare Ag filed Critical Bayer Healthcare Ag
Priority to EP05823841A priority Critical patent/EP1824474A1/en
Publication of WO2006061214A1 publication Critical patent/WO2006061214A1/en

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Classifications

    • 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
    • A61K31/275—Nitriles; Isonitriles
    • A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/235—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group
    • A61K31/24—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids having an aromatic ring attached to a carboxyl group having an amino or nitro group
    • A61K31/245—Amino benzoic acid types, e.g. procaine, novocaine
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • 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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A61P33/12—Schistosomicides

Definitions

  • This invention relates to an anthelmintic composition.
  • Praziquantel and Oxyclosanide are known anthelmintics and, for this purpose, are generally available in suspensions. Although fairly effective, the suspensions do suffer the disadvantage that they are difficult to formulate and are relatively limited as to the amount of immediately bioavailable active compound that they contain.
  • an anthelmintic composition comprising an active ingredient selected from any one or more of Praziquantel, Closantel Sodium, Levimasole and Oxyclosanide dissolved in propylene glycol.
  • compositions to contain between 0.5 and 4%m/v Praziquantel, preferably 2.8%m/v Praziquantel; alternatively for the composition to contain between 1 and 5%m/v Levimasole, preferably 2.5 to 3.75%m/v Levimasole; further alternatively for the composition to contain between 1 and 5%m/v Oxyclosanide, preferably 2.55% Oxyclosanide; still further alternatively for the composition to contain between 1 and 4%m/v Closantel Sodium, preferably 2.5% Closantel Sodium.
  • compositions according to the present invention may contain Chlorbutanol and/or benzyl alcohol.
  • Preferred concentrations of Chlorbutanol are 2 to 5%m/v, in particular 3,3 to 4,l%m/v; preferred concentrations of benzyl alcohol are 1 to 4%m/v, in particular 2,3 to 2,8%m/v.
  • a suitable amount of an active ingredient selected from Praziquantel, Levimasole and Oxyclosanide was dissolved in propylene glycol to provide the solutions of varying concentration. These solutions were tested against suspensions that are available on the market to find concentrations in solution have the same efficacy as suspensions. The results are shown in table below.
  • Solution 2 uses has a higher concentration of Praziquantel than the Endotape Suspension. This concentration was selected simply to match that of Solution 1 but it has nonetheless been found that Solution 2 is effective against a much broader spectrum of tape worms than the Endotape Suspension.
  • Chlorbutanol and benzyl alcohol are defined as preservatives, in this formulation they function as free radical scavengers, possibly due to their OH groups. According to this theory, degradation releases free radicals, and these free radicals function as a catalyst for further degradation. Hence the preservatives, by functioning as free radical scavengers, retard the degradation process.
  • solutions of the invention are easy to formulate, contain less excipients and are more effective than prior art suspensions and highly effective. It will be appreciated, however, that many other embodiments of anthelmintic solutions exists which fall within the scope of the invention, particularly as regards the concentration of the active ingredient.

Abstract

An anthelmintic composition is provided which includes an active ingredient selected from any one or more of Praziquantel, Closantel Sodium, Levimasole and Oxyclosanide dissolved in propylene glycol.

Description

ANTHELMINTIC COMPOSITION
FIELD OF THE INVENTION
This invention relates to an anthelmintic composition.
BACKGROUND TO THE INVENTION
Praziquantel and Oxyclosanide are known anthelmintics and, for this purpose, are generally available in suspensions. Although fairly effective, the suspensions do suffer the disadvantage that they are difficult to formulate and are relatively limited as to the amount of immediately bioavailable active compound that they contain.
OBJECT OF THE INVENTION
It is an object of this invention to provide an anthelmintic composition which at least partially alleviates the abovementioned problem.
SUMMARY OF THE INVENTION
In accordance with this invention there is provided an anthelmintic composition comprising an active ingredient selected from any one or more of Praziquantel, Closantel Sodium, Levimasole and Oxyclosanide dissolved in propylene glycol.
Further features of the invention provide for the composition to contain between 0.5 and 4%m/v Praziquantel, preferably 2.8%m/v Praziquantel; alternatively for the composition to contain between 1 and 5%m/v Levimasole, preferably 2.5 to 3.75%m/v Levimasole; further alternatively for the composition to contain between 1 and 5%m/v Oxyclosanide, preferably 2.55% Oxyclosanide; still further alternatively for the composition to contain between 1 and 4%m/v Closantel Sodium, preferably 2.5% Closantel Sodium.
Moreover, the compositions according to the present invention may contain Chlorbutanol and/or benzyl alcohol. Preferred concentrations of Chlorbutanol are 2 to 5%m/v, in particular 3,3 to 4,l%m/v; preferred concentrations of benzyl alcohol are 1 to 4%m/v, in particular 2,3 to 2,8%m/v.
Embodiments of the invention are described, by way of example only, in the following example. EXAMPLE 1
A suitable amount of an active ingredient selected from Praziquantel, Levimasole and Oxyclosanide was dissolved in propylene glycol to provide the solutions of varying concentration. These solutions were tested against suspensions that are available on the market to find concentrations in solution have the same efficacy as suspensions. The results are shown in table below.
Figure imgf000003_0001
From these results it will be noted that lower amounts of the active compounds can be used to achieve efficacies equal to those of the prior art suspensions. It must be noted that Solution 2 uses has a higher concentration of Praziquantel than the Endotape Suspension. This concentration was selected simply to match that of Solution 1 but it has nonetheless been found that Solution 2 is effective against a much broader spectrum of tape worms than the Endotape Suspension.
It is suspected that the better efficacy of the solutions according to the invention is as a result of better bioavailability than the suspensions.
In Solution 1, Praziquantel is dissolved in 100% undiluted propylene glycol together with 3,7 %m/v Chlorbutanol and 2,5%m/v benzyl alcohol. Normally concentrations of propylene glycol in excess of 70% are considered to be self preserving due to the osmotic effect created by the concentrate propylene glycol on micro organisms. Thus it appears counter-intuitive that, although 100% propylene glycol is used and the product should thus be self preserving, the preservatives Chlorbutanol and benzyl alcohol are also included. During development it was found that if these "preservatives" were not included the stability of the product was severely effected in that the shelf life was severely reduced. It is thus surmised that although Chlorbutanol and benzyl alcohol are defined as preservatives, in this formulation they function as free radical scavengers, possibly due to their OH groups. According to this theory, degradation releases free radicals, and these free radicals function as a catalyst for further degradation. Hence the preservatives, by functioning as free radical scavengers, retard the degradation process.
The solutions of the invention are easy to formulate, contain less excipients and are more effective than prior art suspensions and highly effective. It will be appreciated, however, that many other embodiments of anthelmintic solutions exists which fall within the scope of the invention, particularly as regards the concentration of the active ingredient.

Claims

- A -CLAIMS
1. An anthelmintic composition comprising an active ingredient selected from any one or more of Praziquantel, Closantel Sodium, Levimasole and Oxyclosanide dissolved in propylene glycol.
2. An anthelmintic composition as claimed in claim 1 wherein the composition contains between 0.5 and 4%m/v Praziquantel.
3. An anthelmintic composition as claimed in claim 2 wherein the composition contains 2.8%m/v Praziquantel.
4. An anthelmintic composition as claimed in any one of the preceding claims wherein the composition contains between 1 and 5%m/v Levimasole.
5. An anthelmintic composition as claimed in claim 4 wherein the composition contains between 2.5 to 3.75%m/v Levimasole.
6. An anthelmintic composition as claimed any one of the preceding claims wherein the composition contains between 1 and 5%m/v Oxyclosanide.
7. An anthelmintic composition as claimed in claim 6 wherein the composition contains 2.55% Oxyclosanide.
8. An anthelmintic composition as claimed in any one of the preceding claims wherein the composition contains between 1 and 4%m/v Closantel Sodium.
9. An anthelmintic composition as claimed in claim 8 wherein the composition contains 2.5% Closantel Sodium.
10. An anthelmintic composition substantially as herein described and as illustrated with reference to Solutions 1 to 4 in Example 1.
PCT/EP2005/013139 2004-12-10 2005-12-08 Anthelmintic composition WO2006061214A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP05823841A EP1824474A1 (en) 2004-12-10 2005-12-08 Anthelmintic composition

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ZA2004-10001 2004-12-10
ZA200410001 2004-12-10

Publications (1)

Publication Number Publication Date
WO2006061214A1 true WO2006061214A1 (en) 2006-06-15

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2005/013139 WO2006061214A1 (en) 2004-12-10 2005-12-08 Anthelmintic composition

Country Status (3)

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EP (1) EP1824474A1 (en)
WO (1) WO2006061214A1 (en)
ZA (1) ZA200704633B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010107791A2 (en) 2009-03-17 2010-09-23 Concert Pharmaceuticals, Inc. Pyrazinoisoquinoline compounds

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2252730A (en) * 1991-02-12 1992-08-19 Ancare Distributors Anthelmintic formulations containing praziquantel
WO1995005812A1 (en) * 1993-08-24 1995-03-02 Ashmont Holdings Limited Anthelmintic formulations
AU711820B3 (en) * 1996-07-30 1999-10-21 Ashmont Holdings Limited Anthelmintic formulations
WO2001089497A2 (en) * 2000-05-23 2001-11-29 Bayer Corporation Praziquantel compositions for treating diseases due to sarcocystis, neospora, toxoplasma and isospora
WO2002094221A1 (en) * 2001-05-18 2002-11-28 Jupitar Pty Ltd Emulsion and dispersion formulations and method
WO2003072113A1 (en) * 2002-02-28 2003-09-04 Norbrook Laboratories Limited Long acting parasiticidal composition containing a salicylanilide compound, a polymeric species and at least one other anti-parasitic compound
WO2004043445A1 (en) * 2002-11-11 2004-05-27 Schering-Plough Ltd. Topical parasiticide formulations and methods of treatment
US20040198676A1 (en) * 2003-04-04 2004-10-07 Soll Mark D. Topical anthelmintic veterinary formulations
WO2005074912A2 (en) * 2004-02-02 2005-08-18 Wyeth Antiparasitic composition containing an organic amine salt of closantel

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2252730A (en) * 1991-02-12 1992-08-19 Ancare Distributors Anthelmintic formulations containing praziquantel
WO1995005812A1 (en) * 1993-08-24 1995-03-02 Ashmont Holdings Limited Anthelmintic formulations
AU711820B3 (en) * 1996-07-30 1999-10-21 Ashmont Holdings Limited Anthelmintic formulations
WO2001089497A2 (en) * 2000-05-23 2001-11-29 Bayer Corporation Praziquantel compositions for treating diseases due to sarcocystis, neospora, toxoplasma and isospora
WO2002094221A1 (en) * 2001-05-18 2002-11-28 Jupitar Pty Ltd Emulsion and dispersion formulations and method
WO2003072113A1 (en) * 2002-02-28 2003-09-04 Norbrook Laboratories Limited Long acting parasiticidal composition containing a salicylanilide compound, a polymeric species and at least one other anti-parasitic compound
WO2004043445A1 (en) * 2002-11-11 2004-05-27 Schering-Plough Ltd. Topical parasiticide formulations and methods of treatment
US20040198676A1 (en) * 2003-04-04 2004-10-07 Soll Mark D. Topical anthelmintic veterinary formulations
WO2005074912A2 (en) * 2004-02-02 2005-08-18 Wyeth Antiparasitic composition containing an organic amine salt of closantel

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010107791A2 (en) 2009-03-17 2010-09-23 Concert Pharmaceuticals, Inc. Pyrazinoisoquinoline compounds

Also Published As

Publication number Publication date
ZA200704633B (en) 2008-09-25
EP1824474A1 (en) 2007-08-29

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