WO2019054967A2 - A pour on veterinary composition comprising eprinomectin - Google Patents

A pour on veterinary composition comprising eprinomectin Download PDF

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Publication number
WO2019054967A2
WO2019054967A2 PCT/TR2018/050097 TR2018050097W WO2019054967A2 WO 2019054967 A2 WO2019054967 A2 WO 2019054967A2 TR 2018050097 W TR2018050097 W TR 2018050097W WO 2019054967 A2 WO2019054967 A2 WO 2019054967A2
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Prior art keywords
pour
weight
veterinary composition
composition according
eprinomectin
Prior art date
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PCT/TR2018/050097
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French (fr)
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WO2019054967A3 (en
Inventor
Ali TÜRKYILMAZ
Ediz Yildirim
Oguz Bas
Yesim MURATOGLU
Original Assignee
Verano Ilac Sanayi Ve Ticaret Anonim Sirketi
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Publication of WO2019054967A2 publication Critical patent/WO2019054967A2/en
Publication of WO2019054967A3 publication Critical patent/WO2019054967A3/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A61K9/0017—Non-human animal skin, e.g. pour-on, spot-on

Definitions

  • the present invention relates to a pour-on veterinary composition
  • a pour-on veterinary composition comprising eprinomectin as active agent, at least one penetration enhancer and least one polymeric material.
  • Eprinomectin is a member of the macrocyclic lactone class of endectocides. It is effective against roundworms (gastrointestinal, respiratory, renal, in the skin, etc.) and, depending on the delivery form and the dosage also against a number of external parasites such as lice, mites and various myiasis. It's chemical structure is shown in the formula I.
  • Eprinomectin have a unique mode of action.
  • Compounds of the class bind selectively and with high affinity to glutamate-gated chloride ion channels which occur in invertebrate nerve and muscle cells. This leads to an increase in the permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell, resulting in paralysis and death of the parasite.
  • Compounds of this class may also interact with other ligand-gated chloride channels, such as those gated by the neurotransmitter gamma-aminobutyric acid (GABA).
  • GABA neurotransmitter gamma-aminobutyric acid
  • this invention provides glycol-ether-based pour-on formulations comprising a composition comprising a flukicide, such as, for example, clorsulon (4-amino-6-trichloroethenyl- 1 ,3 - benzene disulfonamide) and/or a macrolide anthelmintic or antiparasitic agent.
  • a flukicide such as, for example, clorsulon (4-amino-6-trichloroethenyl- 1 ,3 - benzene disulfonamide
  • the invention provides pour-on formulations comprising at least one active agent, a glycol ether, and a stability enhancer.
  • polyvinylpyrrolidone is used as polymeric agent. This provide synergistic effect so the drug is bound to the skin with the aid of the polymer which remains on the skin surface after the solvents have evaporated following application. The remaining eprinomectin is released by diffusion and/or erosion of the polymer. Further, this polymeric agent provides stability of pour-on composition.
  • denatonium benzoate is used as bittering agent to discourage the inhalation or ingestion of toxic substances.
  • this bittering agent animals do not interest in drug and animal poisoning does not happen.
  • liquid composition is homogeneous and is more consistent meaning that it does not crystallise, separate or settle out during the shelf-life.
  • the main object of the present invention is to bound the drug to the skin and at same time, evaporating liquid composition following application.
  • a further object of the present invention is to provide stability and homogeneous in pour on composition. Another aim of the invention is to provide such a formulation that is quick and easy to use and entirely compatible with use on herds or flocks containing a large number of animals. A further object of the present invention is to prevent animal poisoning by using bittering agent in pour on composition.
  • the formulation is non-flammable, it is not readily washable by rain, it has good spreadability and cold temperature usage and has good compatibility with currently available dosing devices.
  • pour-on composition is understood to refer to a ready-to-use solution intended to be applied topically and locally on the animal, preferably on the animal's back and at several points or along the line of the back, and applied in low volume.
  • the composition is advantageous as it allows the antiparasitic compound to be absorbed steadily through the skin over a period of time. This avoids or reduces the risk of blood level peaks and troughs commonly encountered with oral dosage forms.
  • the formulation also unexpectedly provides a zero milk withdrawal time for topically applied antiparasitic agents with regard to dairy animals.
  • the pour on veterinary composition comprises eprinomectin as active agent, at least one penetration enhancer and at least one polymeric material wherein the amount of polymeric material in the composition is 0.05% to 20% by weight.
  • the amount of polymeric material in the composition is 0.1 % to 12% by weight, preferably it is 0.15% to 2.0% by weight.
  • the amount of eprinomectin in the composition is 0.05% to 20.0% by weight, preferably it is 0.1 % to 12.0% by weight.
  • the polymeric material helps to keep the drug at the skin level longer by remaining on the skin surface after the solvents have evaporated following application.
  • the remaining eprinomectin and polymeric agent does not change the appearance of the animal's hair coat and the eprinomectin is released by diffusion and/or erosion of the polymer.
  • the polymeric materials are selected from the group comprising polyvinylpyrrolidone, polyvinyl alcohol, methyl cellulose, ethyl cellulose, carboxy methyl cellulose, hydroxyethyl cellulose, hydrolyzed wheat protein, hydrolyzed animal protein, gelatin derivatives, collagen derivatives, acrylates/tOctylpropenamide copolymer and cationic quatenary amine salts or mixtures thereof, preferably the polymeric material is polyvinylpyrrolidone.
  • the composition comprises a penetration enhancer.
  • This penetration enhancer facilitates the delivery of the antiparasitic agent through the animals's skin.
  • Suitable the penetration enhancers are selected from the group comprising propylene glycol dicaprylate/dicaprate, cetearyl ethylhexanoate, isopropyl myristate, azones, fatty acids and alcohols, terpenes, terpenoids, oxazolidinones, butyl stearate, C12-C15 alkyl benzoate, cetyl palmiate, di- isopropyl adipate, di-ethylhexyl adipate, caprylic/capric triglyceride, isocetyl stearate, isopropyl palmitate, lauryl lactate, myristyl myristate, ethylhexyl cocoate, ethylhexyl hydroxystearate, ethylhexyl palmitate, ethylhexyl pelargonate, ethylhexyl stearate,
  • the amount of the penetration enhancers is 22.0% to 50.0% by weight.
  • the pour on veterinary composition further comprises pharmaceutically acceptable excipients which are selected from the group comprising bittering agent, antioxidant or mixtures thereof.
  • bittering agents are selected from the group comprising denatonium benzoate, sucrose octaacetate, quercetin, brucine, quassin or mixtures thereof, preferably the bittering agent is denatonium benzoate.
  • Bittering agents can be present in an amount of from about 0 to about 0.1 % weight/volume (w/v), preferably in an amount of about 0.000001 to about 0.1 % w/v.
  • Suitable the antioxidants are selected from the group comprising BHT (butylated hydroxy toluene), propyl gal late, BHA (butylated hydroxy anisole), monothioglycerol or mixtures thereof, preferably the antioxidant is BHT (butylated hydroxy toluene). The amount of butylated hydroxy toluene is 0.001 % to 5.0% by weight.
  • the weight ratio of denatonium benzoate to butylated hydroxy toluene is 0.000001 -2.0, preferably the ratio is 0.00001 -1 .0 in composition.
  • the solvent may be water or an alcohol. Suitable the solvent is alcohol.
  • the alcohol is selected from the group comprising isopropyl alcohol, benzyl alcohol, propylene glycol, polyethylene glycol, ethanol, glycerine, cyclomethicone, glycerine triacetate, diethylene glycol monoethyl ether, glycerol formal, propylene carbonate or mixtures thereof, preferably the alcohol is isopropyl alcohol.
  • the composition comprises: 0.05 - 20.0% by weight of eprinomectin, 0.05 - 20.0% by weight of polyvinylpyrrolidone, 20.0 - 45.0% by weight of propylene glycol dicaprylate/dicaprate, 2.0 - 8.0% by weight of cetearyl ethylhexanoate and isopropyl myristate, 35.0 - 65.0% by weight of isopropyl alcohol, 0.000001 - 0.1 % weight/volume of denatonium benzoate, 0.001 - 5.0% by weight of butylated hydroxy toluene.
  • process for preparing the pour on veterinary composition comprises the following steps:
  • step(e) adding propylene glycol dicaprylate/dicaprate, cetearyl ethylhexanoate and isopropyl myristate to step(e) the mixture
  • This example describes a pour on veterinary composition
  • eprinomectin The active ingredient and excipients of the tablet are given below:
  • the volume is then adjusted to 100% by the addition of the final volume of isopropyl alcohol, with the solution being mixed until it becomes homogeneous.
  • This example describes a pour on veterinary composition
  • eprinomectin The active ingredient and excipients of the tablet are given below:
  • a process for example 1 and example 2 comprises the following steps:
  • step(e) adding propylene glycol dicaprylate/dicaprate (crodamol PC), ethylhexanoate and isopropyl myristate (crodamol CAP) to step(e) the mixture g) adding isopropyl alcohol to step(f) until the volume adjusted to 100%.
  • crodamol PC propylene glycol dicaprylate/dicaprate
  • crodamol CAP isopropyl myristate

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Agronomy & Crop Science (AREA)
  • Plant Pathology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Pest Control & Pesticides (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)

Abstract

The present invention relates to a pour-on veterinary composition, comprising eprinomectin as active agent, at least one penetration enhancer and least one polymeric material.

Description

A POUR ON VETERINARY COMPOSITION COMPRISING EPRINOMECTIN
Field of Invention
The present invention relates to a pour-on veterinary composition comprising eprinomectin as active agent, at least one penetration enhancer and least one polymeric material. Background of Invention
Eprinomectin is a member of the macrocyclic lactone class of endectocides. It is effective against roundworms (gastrointestinal, respiratory, renal, in the skin, etc.) and, depending on the delivery form and the dosage also against a number of external parasites such as lice, mites and various myiasis. It's chemical structure is shown in the formula I.
Figure imgf000002_0001
Formula I
Eprinomectin have a unique mode of action. Compounds of the class bind selectively and with high affinity to glutamate-gated chloride ion channels which occur in invertebrate nerve and muscle cells. This leads to an increase in the permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell, resulting in paralysis and death of the parasite. Compounds of this class may also interact with other ligand-gated chloride channels, such as those gated by the neurotransmitter gamma-aminobutyric acid (GABA). The margin of safety for compounds of this class is attributable to the fact that mammals do not have glutamate-gated chloride channels, the macrocyclic lactones have a low affinity for other mammalian ligand-gated chloride channels and they do not readily cross the blood-brain barrier. Pour-on formulations are described in U.S. Patent No. 6,010,710, incorporated herein by reference. The patent application WO2009070687 discloses a formulation. The aplication relates to pour-on formulations for combating parasites in animals. In some embodiments, this invention provides glycol-ether-based pour-on formulations comprising a composition comprising a flukicide, such as, for example, clorsulon (4-amino-6-trichloroethenyl- 1 ,3 - benzene disulfonamide) and/or a macrolide anthelmintic or antiparasitic agent. In other embodiments, the invention provides pour-on formulations comprising at least one active agent, a glycol ether, and a stability enhancer.
In comparison to prior art, according to present invention polyvinylpyrrolidone is used as polymeric agent. This provide synergistic effect so the drug is bound to the skin with the aid of the polymer which remains on the skin surface after the solvents have evaporated following application. The remaining eprinomectin is released by diffusion and/or erosion of the polymer. Further, this polymeric agent provides stability of pour-on composition.
In addition, according to present invention denatonium benzoate is used as bittering agent to discourage the inhalation or ingestion of toxic substances. Thus, thanks to this bittering agent, animals do not interest in drug and animal poisoning does not happen.
The other advantage of the above solutions is that the liquid composition is homogeneous and is more consistent meaning that it does not crystallise, separate or settle out during the shelf-life.
Detailed description of the Invention
The main object of the present invention is to bound the drug to the skin and at same time, evaporating liquid composition following application.
A further object of the present invention is to provide stability and homogeneous in pour on composition. Another aim of the invention is to provide such a formulation that is quick and easy to use and entirely compatible with use on herds or flocks containing a large number of animals. A further object of the present invention is to prevent animal poisoning by using bittering agent in pour on composition.
Additional advantages of this invention are that the formulation is non-flammable, it is not readily washable by rain, it has good spreadability and cold temperature usage and has good compatibility with currently available dosing devices.
The concentration of the active compound in the milk of dairy animals below a safe concentration for human consumption.
The expression "pour-on composition" is understood to refer to a ready-to-use solution intended to be applied topically and locally on the animal, preferably on the animal's back and at several points or along the line of the back, and applied in low volume. The composition is advantageous as it allows the antiparasitic compound to be absorbed steadily through the skin over a period of time. This avoids or reduces the risk of blood level peaks and troughs commonly encountered with oral dosage forms. The formulation also unexpectedly provides a zero milk withdrawal time for topically applied antiparasitic agents with regard to dairy animals.
According to all these embodiments, the pour on veterinary composition comprises eprinomectin as active agent, at least one penetration enhancer and at least one polymeric material wherein the amount of polymeric material in the composition is 0.05% to 20% by weight.
According to this embodiment, the amount of polymeric material in the composition is 0.1 % to 12% by weight, preferably it is 0.15% to 2.0% by weight.
According to this embodiment, the amount of eprinomectin in the composition is 0.05% to 20.0% by weight, preferably it is 0.1 % to 12.0% by weight.
The polymeric material helps to keep the drug at the skin level longer by remaining on the skin surface after the solvents have evaporated following application. The remaining eprinomectin and polymeric agent does not change the appearance of the animal's hair coat and the eprinomectin is released by diffusion and/or erosion of the polymer. Suitable the polymeric materials are selected from the group comprising polyvinylpyrrolidone, polyvinyl alcohol, methyl cellulose, ethyl cellulose, carboxy methyl cellulose, hydroxyethyl cellulose, hydrolyzed wheat protein, hydrolyzed animal protein, gelatin derivatives, collagen derivatives, acrylates/tOctylpropenamide copolymer and cationic quatenary amine salts or mixtures thereof, preferably the polymeric material is polyvinylpyrrolidone.
According to this embodiment of the invention, the composition comprises a penetration enhancer. This penetration enhancer facilitates the delivery of the antiparasitic agent through the animals's skin.
Suitable the penetration enhancers are selected from the group comprising propylene glycol dicaprylate/dicaprate, cetearyl ethylhexanoate, isopropyl myristate, azones, fatty acids and alcohols, terpenes, terpenoids, oxazolidinones, butyl stearate, C12-C15 alkyl benzoate, cetyl palmiate, di- isopropyl adipate, di-ethylhexyl adipate, caprylic/capric triglyceride, isocetyl stearate, isopropyl palmitate, lauryl lactate, myristyl myristate, ethylhexyl cocoate, ethylhexyl hydroxystearate, ethylhexyl palmitate, ethylhexyl pelargonate, ethylhexyl stearate, di-ethylhexyl succinate, PPG- 2 myristyl ether propionate, pentaerythrityl tetraisostearate, pentaerythrityl tetracaprylate, pentaerythrityl tetracaprate, cetyl esters, isotridecyl isononanoate, stearyl heptanoate, steryl caprylate or mixtures thereof, preferably the penetration enhancers are propylene glycol dicaprylate/dicaprate, cetearyl ethylhexanoate and isopropyl myristate.
According to this embodiment, the amount of the penetration enhancers is 22.0% to 50.0% by weight.
The pour on veterinary composition further comprises pharmaceutically acceptable excipients which are selected from the group comprising bittering agent, antioxidant or mixtures thereof.
Suitable the bittering agents are selected from the group comprising denatonium benzoate, sucrose octaacetate, quercetin, brucine, quassin or mixtures thereof, preferably the bittering agent is denatonium benzoate. Bittering agents can be present in an amount of from about 0 to about 0.1 % weight/volume (w/v), preferably in an amount of about 0.000001 to about 0.1 % w/v. Suitable the antioxidants are selected from the group comprising BHT (butylated hydroxy toluene), propyl gal late, BHA (butylated hydroxy anisole), monothioglycerol or mixtures thereof, preferably the antioxidant is BHT (butylated hydroxy toluene). The amount of butylated hydroxy toluene is 0.001 % to 5.0% by weight.
According to this embodiment of the invention, the weight ratio of denatonium benzoate to butylated hydroxy toluene is 0.000001 -2.0, preferably the ratio is 0.00001 -1 .0 in composition.
The solvent may be water or an alcohol. Suitable the solvent is alcohol. The alcohol is selected from the group comprising isopropyl alcohol, benzyl alcohol, propylene glycol, polyethylene glycol, ethanol, glycerine, cyclomethicone, glycerine triacetate, diethylene glycol monoethyl ether, glycerol formal, propylene carbonate or mixtures thereof, preferably the alcohol is isopropyl alcohol. According to this embodiment, the composition comprises: 0.05 - 20.0% by weight of eprinomectin, 0.05 - 20.0% by weight of polyvinylpyrrolidone, 20.0 - 45.0% by weight of propylene glycol dicaprylate/dicaprate, 2.0 - 8.0% by weight of cetearyl ethylhexanoate and isopropyl myristate, 35.0 - 65.0% by weight of isopropyl alcohol, 0.000001 - 0.1 % weight/volume of denatonium benzoate, 0.001 - 5.0% by weight of butylated hydroxy toluene.
According to this embodiment, process for preparing the pour on veterinary composition comprises the following steps:
a) dissolving eprinomectin in isopropyl alcohol
b) dissolving butyl hydroxyl toluene in isopropyl alcohol
c) dissolving denatonium benzoate in isopropyl alcohol
d) dissolving polyvinylpyrrolidone in isopropyl alcohol
e) after, mixing prepared the four solutions
f) adding propylene glycol dicaprylate/dicaprate, cetearyl ethylhexanoate and isopropyl myristate to step(e) the mixture
g) adding isopropyl alcohol to step(f) until the volume adjusted to 100%. Example 1
This example describes a pour on veterinary composition comprising eprinomectin. The active ingredient and excipients of the tablet are given below:
The pour on veterinary composition of eprinomectin.
Figure imgf000007_0001
The volume is then adjusted to 100% by the addition of the final volume of isopropyl alcohol, with the solution being mixed until it becomes homogeneous.
Example 2
This example describes a pour on veterinary composition comprising eprinomectin. The active ingredient and excipients of the tablet are given below:
The pour on veterinary composition of eprinomectin.
Figure imgf000007_0002
The volume is then adjusted to 100% by the addition of the final volume of isopropyl alcohol, with the solution being mixed until it becomes homogeneous. A process for example 1 and example 2 comprises the following steps:
a) dissolving eprinomectin in 3.5 kg isopropyl alcohol
b) dissolving butyl hydroxyl toluene in 3.5 kg isopropyl alcohol
c) dissolving denatonium benzoate in 3.5 kg isopropyl alcohol
d) dissolving polyvinylpyrrolidone in 3.5 kg isopropyl alcohol
e) after, mixing prepared four solutions
f) adding propylene glycol dicaprylate/dicaprate (crodamol PC), ethylhexanoate and isopropyl myristate (crodamol CAP) to step(e) the mixture g) adding isopropyl alcohol to step(f) until the volume adjusted to 100%.

Claims

1 . A pour on veterinary composition comprising;
a. eprinomectin as active agent
b. at least one penetration enhancer
c. at least one polymeric material
wherein the amount of polymeric material in the composition is 0.05% to 20.0% by weight.
2. The pour on veterinary composition according to claim 1 , wherein the amount of polymeric material in the composition is 0.1 % to 12% by weight, preferably it is 0.15% to 2.0% by weight.
3. The pour on veterinary composition according to claim 2, wherein the amount of eprinomectin in the composition is 0.05% to 20.0% by weight, preferably it is 0.1 % to 12.0% by weight.
4. The pour on veterinary composition according to claim 3, wherein the polymeric materials are selected from the group comprising polyvinylpyrrolidone, polyvinyl alcohol, methyl cellulose, ethyl cellulose, carboxy methyl cellulose, hydroxyethyl cellulose, hydrolyzed wheat protein, hydrolyzed animal protein, gelatin derivatives, collagen derivatives, acrylates/tOctylpropenamide copolymer and cationic quatemary amine salts or mixtures thereof, preferably the polymeric material is polyvinylpyrrolidone.
5. The pour on veterinary composition according to any preceding claims, wherein the penetration enhancers are selected from the group comprising propylene glycol dicaprylate/dicaprate, cetearyl ethylhexanoate, isopropyl myristate, azones, fatty acids and alcohols, terpenes, terpenoids, oxazolidinones, butyl stearate, C12-C15 alkyl benzoate, cetyl palmiate, di-isopropyl adipate, di-ethylhexyl adipate, caprylic/capric triglyceride, isocetyl stearate, isopropyl palmitate, lauryl lactate, myristyl myristate, ethylhexyl cocoate, ethylhexyl hydroxystearate, ethylhexyl palmitate, ethylhexyl pelargonate, ethylhexyl stearate, di-ethylhexyl succinate, PPG- 2 myristyl ether propionate, pentaerythrityl tetraisostearate, pentaerythrityl tetracaprylate, pentaerythrityl tetracaprate, cetyl esters, isotridecyl isononanoate, stearyl heptanoate, steryl caprylate or mixtures thereof, preferably the penetration enhancers are propylene glycol dicaprylate/dicaprate, cetearyl ethylhexanoate and isopropyl myristate.
6. The pour on veterinary composition according to claim 5, wherein the amount of the penetration enhancers is 22.0 % to 50.0% by weight.
7. The pour on veterinary composition according any preceding claims, further comprising pharmaceutically acceptable excipients which are selected from the group comprising bittering agent, antioxidant or mixtures thereof.
8. The pour on veterinary composition according to claim 7, wherein the bittering agents are selected from the group comprising denatonium benzoate, sucrose octaacetate, quercetin, brucine, quassin or mixtures thereof, preferably it is denatonium benzoate.
9. The pour on veterinary composition according to claim 8, wherein the amount of denatonium benzoate is 0.000001 % to 0.1 % weight/volume.
10. The pour on veterinary composition according to claim 7, wherein the antioxidants are selected from the group comprising butylated hydroxy toluene, propyl gal late, butylated hydroxy anisole, monothioglycerol or mixtures thereof, preferably antioxidant is butylated hydroxy toluene.
1 1 . The pour on veterinary composition according to claim 10, wherein the amount of butylated hydroxy toluene is 0.001 % to 5.0% by weight.
12. The pour on veterinary composition according to claim 9 or 1 1 , wherein the weight ratio of denatonium benzoate to butylated hydroxy toluene is 0.000001 - 2.0, preferably the ratio is 0.00001 -1 .0 in composition.
13. The pour on veterinary composition according to any preceding claims, further comprising the solvent is selected from water or alcohol, preferably the solvent is alcohol. 14. The pour on veterinary composition according to any preceding claims, wherein the composition comprises:
0.05 - 20.0% by weight of eprinomectin
0.05 - 20.0% by weight of polyvinylpyrrolidone
20.0 - 45.0% by weight of propylene glycol dicaprylate/dicaprate,
2.0 - 8.0% by weight of cetearyl ethylhexanoate and isopropyl myristate
35.0 - 65.0% by weight of isopropyl alcohol
0.000001 - 0.1 % weigth/volume of denatonium benzoate
0.001 - 5.0% by weight of butylated hydroxy toluene
15. A process for preparing the pour on veterinary composition according to claim 14, comprising the following steps:
a) dissolving eprinomectin in isopropyl alcohol
b) dissolving butyl hydroxyl toluene in isopropyl alcohol
c) dissolving denatonium benzoate in isopropyl alcohol
d) dissolving polyvinylpyrrolidone in isopropyl alcohol
e) after, mixing prepared the four solutions
f) adding propylene glycol dicaprylate/dicaprate, cetearyl ethylhexanoate and isopropyl myristate to step(e) the mixture
g) adding isopropyl alcohol to step(f) until the volume adjusted to 100%.
PCT/TR2018/050097 2017-03-15 2018-03-14 A pour on veterinary composition comprising eprinomectin WO2019054967A2 (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6010710A (en) 1996-03-29 2000-01-04 Merial Direct pour-on skin solution for antiparasitic use in cattle and sheep
WO2009070687A1 (en) 2007-11-26 2009-06-04 Merial Limited Solvent systems for pour-on formulations for combating parasites

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RO115102B1 (en) * 1993-05-10 1999-11-30 Merck & Co Inc Avermectin topical formulation and processes for preparing the same
PL1610613T3 (en) * 2003-04-04 2017-06-30 Merial, Inc. Topical anthelmintic veterinary formulations
GB0316377D0 (en) * 2003-07-12 2003-08-13 Norbrook Lab Ltd Parasiticidal composition

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6010710A (en) 1996-03-29 2000-01-04 Merial Direct pour-on skin solution for antiparasitic use in cattle and sheep
WO2009070687A1 (en) 2007-11-26 2009-06-04 Merial Limited Solvent systems for pour-on formulations for combating parasites

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