NZ210247A - Anthelmintic compositions containing levamisole derivatives - Google Patents
Anthelmintic compositions containing levamisole derivativesInfo
- Publication number
- NZ210247A NZ210247A NZ210247A NZ21024784A NZ210247A NZ 210247 A NZ210247 A NZ 210247A NZ 210247 A NZ210247 A NZ 210247A NZ 21024784 A NZ21024784 A NZ 21024784A NZ 210247 A NZ210247 A NZ 210247A
- Authority
- NZ
- New Zealand
- Prior art keywords
- glycofurol
- levamisole
- composition according
- dimethyl isosorbide
- solvent
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed 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
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- 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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
Description
New Zealand Paient Spedficaiion for Paient Number £10247
12 i02 A 7
N.Z. PATENT OFFICE
19 NOV 1984
Priority [)ate{s): Z/~ II
* *
Corr Clas:
°PeClfiCaf'ior> f//ecf; '9.7JAt84
NEW ZEALAND
p^iCS„on 0;te;; e p«P. Journal, pj0. /AHlK ®
frl.30 501
PATENTS ACT 1953 PATENTS FORM No. 5 COMPLETE SPECIFICATION "NEW ANTHELMINTIC COMPOSITIONS"
WE, MAY & BAKER LIMITED, a British Company of Dagenham, Essex, Rrn10 7XS, 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
- 1 - (followed by Page la)
2 10247
- 1 a-
-dcscripti-sk
-^CW ANTHELMINTIC COMPOSITIONS"
This invention relates to new formulations of an organic salt having anthelmintic properties, to processes for the preparation of such formulations and to their use in combatting helminthiasis. 5 Levamisole (L-2,3,5,6-tetrahydro-6-phenyl-
imidazo-[2,1-b]-thiazole), which is widely-used to control intestinal nematodes and lungworm in warm-blooded animals, and nitroxynil (4-cyano-2-iodo-6-nitrophenol or 4-hydroxy-3-iodo-5-nitrobenzonitrile), 10 which is widely-used to control trematode and certain nematode parasites in warm-blooded animals, form a salt, hereinafter referred to as the nitroxynil salt of levamisole, which is as to be expected from the known basic nature of levamisole which is generally 15 provided and used in the form of its hydrochloride or dihydrogen phosphate salts, and the known acid nature of nitroxynil, which is commercially available in the form of an aqueous solution of the eglumine (N-ethyl-D-glucamine) salt of nitroxynil. The nitroxynil salt 20 of levamisole combines the activity of levamisole against nematodes, for example Haemonchus contor tus, Ostertagia spp., Tr ichostrongylus spp., e.g. Tr ichostrongylus axe i, Cooper i a spp., e.g. Cooper i a
«/
21024
oncophora, Nematodirus spp., e.g. Nematodirus fillicolis, Oesaphagostomum spp., e.g. Oesaphagostomum venulosum, Strongyloides spp., e.g. Strongyloides papillosus, Bunostomum spp., e.g. Bunostomum 5 trigonocephalum, Chabertia spp., e.g. Chabertia ovina, Tr ichur is spp., e.g. Tr ichur is ovis , and D ictyocaulus spp., e.g. Dictyocaulus filaria and Dictyocaulus viviparus, and the activity of nitroxynil against trematodes, for example Fasciola hepatica and Fasciola 10 gigantica, and certain nematodes, e.g. Haemonchus contortus, Bunostomum spp, Oesaphagostomum spp, and Parafilaria bovicola. The nitroxynil salt of levamisole may be used to kill internal helminth, e.g. nematode and trematode, parasites of 15 warm-blooded animals, for example cattle, sheep, pigs, goats, horses and dogs. The dosage used depends upon the nature of the helminths, the animal being treated and the route of administration but the administration of a single dose of the nitroxynil salt of levamisole 20 at dosage levels of from 10 to 30 milligrams, and usually about 18 milligrams of the salt per kilogram of animal body weight, generally gives satisfactory control of the parasites. Administration may be parenteral, i.e. by intravenous, intramuscular or 25 subcutaneous injection, oral, e.g. in an oral dosage form such as a tablet, bolus, capsule or drench, as an
2102 4 7
additive to feed, or dermally by a 'pour-on' dosage form, administration of an effective dose in a single unit dose, more especially a single parenteral unit dose, being preferred.
The nitroxynil salt of levamisole may be prepared by the reaction of stoichiometric quantities of nitroxynil and levamisole in water or an inert organic solvent, e.g. ethanol, or by the reaction in water of stoichiometric quantities of a water-soluble 10 salt of nitroxynil, for example the sodium, meglumine (N-methyl-D-glucamine) or eglumine salt and a water-soluble salt of levamisole, for example the hydrochloride or dihydrogen phosphate salt. The aforesaid salts of nitroxynil and levamisole are 15 commercially available or may be readily prepared by known methods from nitroxynil and levamisole, which are themselves commercially available or may be prepared by known methods. (By the term 'known methods' as used in the present specification is meant 20 methods heretofore used or described in the chemical literature). The following procedure illustrates the preparation of the nitroxynil salt of levamisole:-Procedure
A solution of the eglumine salt of nitroxynil 25 (63.05g; 0.125 moles) in water (100ml) was added slowly, with stirring at ambient temperature, to a
2 10247
~ 4 ~
solution of levamisole hydrochloride (29.12g; 0.125 moles) in water (100ml). After completion of the addition, the precipitate which formed was removed by filtration, washed with water and dried i_n vacuo, to give the nitroxynil salt of levamisole (60.2g), m.p. 129°C, in the form of yellow needles.
For parenteral administration to animals, it is desirable to provide a sterile solution suitable for injection which contains an amount of the nitroxynil salt of levamisole in a pharmaceutically acceptable solvent enabling the desired dose to be administered in a single unit dose and which is well tolerated by the animal. Desirably, such solutions would contain from 5 to 70% w/v (weight/volume), and particularly from 5 to 407o w/v, of the nitroxynil salt of levamisole.
The nitroxynil salt of levamisole is only sparingly soluble in water and suspensions of the salt have been found to be poorly tolerated by parenteral administration to animals, even when additives expected to reduce local intolerance are included in the suspensions. Suitable solvents to give solutions of the nitroxynil salt of levamisole which have been mentioned are pharmaceutically-acceptable alcohols, e.g. benzyl alcohol and tetrahydrofurfuryl alcohol, ketones, esters, e.g. ethyl lactate, amides, e.g.
2102
" 5 "
N-(2-hydroxyethyl)lactamide, sulphoxides, e.g. dimethylsulphoxide, sulphones, e.g. sulpholane, cyclic ether derivatives, formals, e.g. glycerol formal, hydrocarbons, perfluorinated hydrocarbons, e.g. perfluorodecalin, glycols and glycol derivatives, e.g. ethylene glycol, propylene glycol, ethylene glycol mono- and di-alkyl ethers, propylene glycol mono- and di-alkyl ethers, poly-propylene glycols, polyethylene glycols, for example polyethylene glycols having an average molecular weight in the range of from 100 to 600, polypropylene glycol mono- and di-alkyl ethers, polyethylene glycol mono- and di-alkyl ethers, for example diethylene glycol dimethyl ether,
pyrrolidones, for example N-methylpyrrolidone and poly (N-vinylpyrrolidone) , silcone oils, for example polymethylsiloxane, aprotic solvents, for example dimethylformamide, dimethylacetamide and tetra-methylurea, and mixtures of such solvents.
As indicated above, it is desirable to be able to prepare solutions of the nitroxynil salt of levamisole which contain from 5 to 40% w/v of the salt, which are well-tolerated on parenteral administration to the animal and which use solvents which are othewise accepted as being suitable for use as the diluent or carrier in a pharmaceutical composition. In practice, it has been found that
^O-lUrl
-6- 210247
these criteria are difficult to achieve. For example, although the nitroxynil salt of levamisole is highly soluble in neat benzyl alcohol, the latter is biologically active, being used at concentrations up 5 to 2% volume/volume as a preservative in liquid pharmaceutical compositions and the use of high concentrations of benzyl alcohol in such compositions is unacceptable and solutions in dimethylsulphoxide and mixtures of N-methylpyrrolidone and polyethylene-10 glycol 400 have been found to be poorly tolerated on parenteral administration to animals. Accordingly, there remains a need for solutions of the nitroxynil salt of levamisole which meet the aforesaid criteria.
it has been found that solutions of the nitroxynil salt of levamisole which meet these criteria, i.e. which can contain up to 40% w/v of the salt, are well-tolerated on parenteral administration to animals and which utilize a solvent which is otherwise 20 accepted as being suitable for use as the diluent or carrier in a liquid pharmaceutical composition can be prepared using dimethyl isosorbide or glycofurol or a mixture of dimethyl isosorbide and glycofurol as the sole diluent or carrier or in admixture with a 25 co-solvent or co-solvents.
As a result of research and experimentation,
I)
210247
The present invention accordingly provides novel pharmaceutical formulations comprising the nitroxynil salt of levamisole in solution in a solvent comprising dimethyl isosorbide and/or glycofurol, and containing up to 40$ w/v 5 of the nitroxynil salt of levamisole. The lower limit of the nitroxynil salt of levamisole content of the compositions according to the present invention is not critical, the salt content being selected such that the required amount of the nitroxynil salt of 10 levamisole is contained in a volume of solution appropriate to the intended purpose. In practice, it is preferred that the nitroxynil salt of levamisole content of the solution is at least 57o w/v, although, as already indicated, lower concentrations may, if 15 desired, be used.
As used in the present specification in respect of solutions according to the present invention, the term 'nitroxynil salt of levamisole' is to be understood to embrace not only the salt formed 20 between nitroxynil and levamisole but also an association of nitroxynil and levamisole in equimolar proportions.
2 10247
Dimethyl isosorbide or glycofurol or mixtures thereof may be used alone as carrier or diluent in pharmaceutical compositions according to the present invention, but if desired one or more co-solvents, for 5 example water, butyrolactone and alcohols, for example,
ethanol, glycols, e.g. ethylene glycol, propylene glycol, polyethylene glycols and polypropylene glycols, glycerol, tetrahydrofurfuryl alcohol and benzyl alcohol, or mixtures thereof may be included. Preferably, the proportion 10 of dimethyl isosorbide or glycofurol or mixtures of dimethyl isosorbide and glycofurol in the solvent should not be less than 25$ "by volume. When mixtures of dimethyl isosorbide and glycofurol are used as the sole diluent or carrier or in association with 15 co-solvents, the ratio of dimethyl isosorbide to glycofurol in the mixture used as the sole diluent or carrier and the ratio of dimethyl 'isosorbide to glycofurol in the dimethyl isosorbide-glycofurol component of diluents or carriers which comprise, in 20 addition, one or more co-solvents can vary widely, for example from 100:1 to 1:100 by volume. Suitable solvents include 80:20$ v/v (volume/volume) mixtures of dimethyl isosorbide and water and 1:1:1 v/v mixtures of dimethyl isosorbide, glycofurol and water.
2102
The pharmaceutical formulations according to the present invention may be used to administer the nitroxynil salt of levamisole to kill internal helminth, e.g. nematode and trematode, parasites of 5 warm-blooded animals, e.g. cattle, sheep, pigs, goats, horses and dogs, at the dosages and for the purposes hereinbefore described for the nitroxynil salt of levamisole, by parenteral administration, i.e. by intravenous, intramuscular or subcutaneous 10 administration, by oral administration as a drench or dermally as a 'pour-on' dosage form, administration of an effective dose of the nitroxynil salt of levamisole in a single unit dose of the pharmaceutical formulation according to the present invention, more 15 especially a single parenteral unit dose, being preferred. Accordingly, there are provided as a preferred feature of the present invention, novel pharmaceutical compositions comprising sterile solutions of the nitroxynil salt of levamisole in 20 dimethyl isosorbide or glycofurol or mixtures of dimethyl isosorbide and glycofurol alone or in admixture with a co-solvent or co-solvents as hereinbefore described, containing up to 407o w/v, and preferably at least 5% w/v, of the nitroxynil salt of
21024
levamisole, wherein, when a co-solvent or co-solvents is present, the proportion of dimethyl isosorbide or glycofurol or mixture thereof in the solvent is preferably at least 257o by volume. As will be 5 appreciated, when administered orally as a drench or dermally by a 'pour-on' dosage form, the pharmaceutical formulations according to the present invention need not be sterile, but sterile formulations may, if desired, be used for these 10 purposes.
The novel pharmaceutical formulations according to the present invention may be prepared by dissolving the nitroxynil salt of levamisole in dimethyl isosorbide or glycofurol or mixture thereof 15 alone or in admixture with a co-solvent or co-solvents as hereinbefore described, or by dissolving stoichiometric amounts of levamisole or a salt thereof, e.g. the hydrochloride or dihydrogen phsophate, and nitroxynil or a salt thereof, e.g. the 20 eglumine, meglumine or sodium salt, in dimethyl isosorbide or glycofurol or mixture thereof alone or in admixture with a co-solvent or co-solvents as hereinbefore described. These dissolutions of the nitroxynil salt of levamisole or levamisole and 25 nitroxynil or salts thereof may be carried out at ambient temperature or with gentle heating, e.g. to 60
210247
- li -
to 70°C and with agitation. The solution thus obtained may then, if desired, be sterilised, for example, by passage through a suitable bacteria-proof filter to give the preferred sterile pharmaceutical 5 compositions according to the present invention suitable for parenteral administration, which are then placed and sealed under sterile conditions in sterile single unit dose or multi-dose containers.
Bases, for example organic bases, e.g.
eglumine, or inorganic bases, e.g. sodium hydroxide,
may, if required, be included in the pharmaceutical compositions according to the present invention to obtain complete dissolution of the nitroxynil salt of levamisole in mixtures of dimethyl isosorbide and/or glycofurol 15 and co-solvents in which the salt is only sparingly soluble, e.g. water, which contains significant proportions of the co-solvent(s) and from which precipitation would otherwise occur.
If desired, biological preservatives, e.g. up 20 to 27c v/v of benzyl alcohol, additives to improve chemical and physical stability on storage, and additives to reduce localised tissue reaction on injection, may be incorporated into the pharmaceutical compositons according to the present invention. 25 Dimethyl isosorbide is offered by 1C1 Americas
Inc. and Atlas Chemicals Industries (UK) Ltd.
Glycofurol is offered by Lusochimica S.p.a.,
Italy.
710247
The following non-limitative examples illustrate the present invention.
EXAMPLE 1
A clear 207o w/v solution of the nitroxynil 5 salt of levamisole was obtained by dissolving nitroxynil (11.7g) and levamisole (8.3g) with stirring at ambient temperature in dimethyl isosorbide (100ml) until dissolution of solid material was complete.
The solution thus obtained was sterilised by 10 passage through a bacteria-proof filter and divided and sealed under sterile conditions into sterile ampoules in quantities such as to give a suitable unit dose for parenteral administration. Sterile solutions similarly prepared may, if desired, be placed and 15 sealed under sterile conditions in sterile multi-dose containers from which suitable unit doses for parenteral administration may be withdrawn for use as required.
EXAMPLE 2
A clear 20% w/v solution of the nitroxynil salt of levamisole in a 80 r 20% v/v mixture of dimethyl isosorbide and water was obtained by adding nitroxynil (11.7g) and levamisole (8.3g), with stirring to a mixture of dimethyl isosorbide (80ml) and water (20ml) 25 and stirring the suspension thus obtained at 40°C until dissolution of solid material was complete.
121024 1
13 -
The solution thus obtained was sterilised by passage through a bacteria-proof filter and divided and sealed under sterile conditions into sterile ampoules in quantities such as to give a suitable unit 5 dose for parenteral administration. Sterile solutions similarly prepared may, if desired, be placed and sealed under sterile conditions in sterile multi-dose containers from which suitable unit doses for parenteral administration may be withdrawn for use as 10 required.
EXAMPLE 3
The nitroxynil salt of levamisole (20g) and eglumine (8.4g) were added, with stirring at 40°C, to a mixture of dimethyl isosorbide (33ml), glycofurol 15 (33ml), water (32ml) and benzyl alcohol (2ml) and stirring at 40°C was continued until dissolution was complete.
The clear 20% w/v solution of the nitroxynil salt of levamisole in a 33:33:32:2% v/v mixture of 20 dimethyl isosorbide, glycofurol, water and benzyl alcohol thus obtained was sterilised by passage through a bacteria-proof filter and divided and sealed under sterile conditions into sterile ampoules in quantities such as to give a suitable unit dose for 25 parenteral administration. Sterile solutions similarly prepared may, if desired, be placed and
Claims (16)
1. A pharmaceutical composition which comprises the nitroxynil salt of levamisole in solution in a solvent comprising dimethyl isosorbide and/or glycofurol, and containing up to 40% w/v of the 5 nitroxynil salt of levamisole.
2. A composition according to claim 1 which comprises at least 5% w/v of the nitroxynil salt of levamisole.
3. A composition according to claim 1 or 2 which 10 comprises one or more co-solvents.
4. A composition according to claim 3 in which the co-solvents are selected from water, butyrolactone and alcohols.
5. A composition according to claim 3 or 4 in 15 which the proportion of dimethyl isosorbide or glycofurol or mixture of dimethyl isosorbide and glycofurol in the solvent is not less than 25% by volume.
6. A composition according to any one of the 20 preceding claims wherein the solvent comprises dimethyl isosorbide and glycofurol in a ratio of dimethyl isosorbide to glycofurol of from 100:1 to 1:100 by volume.
7. A composition according to any one of the 25 preceding claims in which the solvent is a mixture of ip - 16 - 2 1 024 dimethyl isosorbide and glycofurol in a ratio of 80:20 v/v.
8. A composition according to any one of claims 1 to 6 in which the solvent is a mixture of 5 dimethyl isosorbide, glycofurol and water in a ratio of 1:1:1 v/v.
9. A composition according to any one of the preceding claims in a form suitable for parenteral or oral administration, or for dermal administration as a 10 pour-on dosage form.
10. A sterile pharmaceutical composition which comprises the nitroxynil salt of levamisole in a solvent comprising dimethyl isosorbide or glycofurol or a mixture of dimethyl isosorbide and glycofurol alone 15 or in admixture with a co-solvent or co-solvents, and containing up to 40% w/v of the nitroxynil salt of levamisole.
11. A composition according to claim 10 which comprises at least 5% w/v of the nitroxynil salt of 20 levamisole.
12. A composition according to claim 10 or 11 wherein, when one or more co-solvents is present the proportion of dimethyl isosorbide or glycofurol or mixture thereof in the solvent is at least 25% v/v. 25
13. A composition according to any one of the preceding claims which comprises a base to obtain complete dissolution of the nitroxynil salt of the 7^(0 - 17 - 210247 levamisole in a solvent comprising dimethyl isosorbide and/or glycofurol and a co-solvent in which the salt is only sparingly soluble.
14. A composition according to any one of the 5 preceding claims in unit dosage form.
15. A composition according to claim 14 for parenteral administration.
16. A pharmaceutical composition according to claim 1 substantially as hereinbefore described in any 10 one of Examples 1, 2, 3 and 4. DATED THIS |C>^~DAY OF 198^7 A. J. ARK & SON PER AGENTS FOR THE APPLICANTS
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB838331037A GB8331037D0 (en) | 1983-11-21 | 1983-11-21 | Compositions of matter |
Publications (1)
Publication Number | Publication Date |
---|---|
NZ210247A true NZ210247A (en) | 1988-01-08 |
Family
ID=10552109
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NZ210247A NZ210247A (en) | 1983-11-21 | 1984-11-19 | Anthelmintic compositions containing levamisole derivatives |
Country Status (15)
Country | Link |
---|---|
JP (1) | JPS60123419A (en) |
AU (1) | AU3564984A (en) |
BE (1) | BE901095A (en) |
CA (1) | CA1236402A (en) |
CH (1) | CH662273A5 (en) |
DE (1) | DE3442402A1 (en) |
DK (1) | DK548884A (en) |
ES (1) | ES8600933A1 (en) |
FR (1) | FR2555047B1 (en) |
GB (2) | GB8331037D0 (en) |
HU (1) | HU196307B (en) |
IT (1) | IT1177262B (en) |
NL (1) | NL8403528A (en) |
NZ (1) | NZ210247A (en) |
ZA (1) | ZA849008B (en) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0147883A3 (en) * | 1983-12-21 | 1986-12-30 | Janssen Pharmaceutica N.V. | Aqueous non-aggressive anthelmintic pour-on formulations |
EP0202568A1 (en) * | 1985-05-13 | 1986-11-26 | Syntex (U.S.A.) Inc. | Anthelmintic compositions |
IT1223343B (en) * | 1987-11-03 | 1990-09-19 | Also Lab Sas | PHARMACEUTICAL FORMULATIONS FOR TRANSDERMAL ADMINISTRATION |
BRPI0506279B1 (en) | 2005-12-16 | 2018-01-09 | Npa - Núcleo De Pesquisas Aplicadas Ltda | SYNERGY COMPOSITION OF ANTIHELMINTICS AND NON-DECATED |
CN100500648C (en) * | 2006-12-29 | 2009-06-17 | 浙江工业大学 | Synthesizing process of nitro iodo phenol cyanide |
BRPI0904365A2 (en) * | 2009-11-05 | 2011-11-16 | Ouro Fino Participacoes E Empreendimentos S A | pharmaceutical associations, pharmaceutical compositions, medicament and method of treating animals |
RU2602189C2 (en) * | 2010-12-27 | 2016-11-10 | Интервет Интернэшнл Б.В. | Topical localized isoxazoline formulation comprising glycofurol |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4082881A (en) * | 1976-12-23 | 1978-04-04 | E. R. Squibb & Sons, Inc. | Topical and other type pharmaceutical formulations containing isosorbide carrier |
AU527154B2 (en) * | 1978-12-15 | 1983-02-17 | Pitman-Moore Australia Limited | Composition and process |
EP0052962B1 (en) * | 1980-11-20 | 1984-05-09 | Beecham Group Plc | Pharmaceutical compositions containing two beta-lactam derivatives |
NZ202422A (en) * | 1981-11-25 | 1985-02-28 | Ici Australia Ltd | D, l-and l-2,3,5,6-tetrahydro-6-phenylimidazo(2,1-b)thiazolium 4-cyano-2-iodo-6-nitrophenoxide and veterinary compositions |
-
1983
- 1983-11-21 GB GB838331037A patent/GB8331037D0/en active Pending
-
1984
- 1984-11-19 JP JP59242550A patent/JPS60123419A/en active Pending
- 1984-11-19 AU AU35649/84A patent/AU3564984A/en not_active Abandoned
- 1984-11-19 DK DK548884A patent/DK548884A/en not_active Application Discontinuation
- 1984-11-19 NZ NZ210247A patent/NZ210247A/en unknown
- 1984-11-19 ZA ZA849008A patent/ZA849008B/en unknown
- 1984-11-20 FR FR8417647A patent/FR2555047B1/en not_active Expired
- 1984-11-20 GB GB08429264A patent/GB2150024B/en not_active Expired
- 1984-11-20 IT IT23660/84A patent/IT1177262B/en active
- 1984-11-20 BE BE0/214033A patent/BE901095A/en not_active IP Right Cessation
- 1984-11-20 DE DE19843442402 patent/DE3442402A1/en not_active Withdrawn
- 1984-11-20 NL NL8403528A patent/NL8403528A/en not_active Application Discontinuation
- 1984-11-20 HU HU844307A patent/HU196307B/en unknown
- 1984-11-20 CA CA000468249A patent/CA1236402A/en not_active Expired
- 1984-11-21 ES ES537825A patent/ES8600933A1/en not_active Expired
- 1984-11-21 CH CH5562/84A patent/CH662273A5/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
IT1177262B (en) | 1987-08-26 |
HU196307B (en) | 1988-11-28 |
GB2150024B (en) | 1987-02-04 |
CH662273A5 (en) | 1987-09-30 |
FR2555047A1 (en) | 1985-05-24 |
CA1236402A (en) | 1988-05-10 |
FR2555047B1 (en) | 1987-04-17 |
JPS60123419A (en) | 1985-07-02 |
AU3564984A (en) | 1985-05-30 |
DK548884D0 (en) | 1984-11-19 |
ES537825A0 (en) | 1985-10-16 |
IT8423660A0 (en) | 1984-11-20 |
BE901095A (en) | 1985-05-20 |
DE3442402A1 (en) | 1985-05-30 |
GB2150024A (en) | 1985-06-26 |
IT8423660A1 (en) | 1986-05-20 |
ZA849008B (en) | 1985-07-31 |
GB8429264D0 (en) | 1984-12-27 |
ES8600933A1 (en) | 1985-10-16 |
GB8331037D0 (en) | 1983-12-29 |
DK548884A (en) | 1985-05-22 |
NL8403528A (en) | 1985-06-17 |
HUT35955A (en) | 1985-08-28 |
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