Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Biocides; animal or insect repellents or attractants
Reexamination Certificate
1998-09-30
2001-02-27
Levy, Neil S. (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Biocides; animal or insect repellents or attractants
C514S030000, C514S937000
Reexamination Certificate
active
06193989
ABSTRACT:
An object of this invention is a new long acting injectable parasiticide composition and the process for its preparation.
Ivermectin is a semisynthetic derivative formed by a mixture of two components, 22,23-dihydroavermectin B
1a
and 22,23-dihydroavermectin B
1b
. Initial avermectin B
1
is a macrocyclic lactone obtained from
Streptomyces avermitilis
culture fermentation broth and the selective hydrogenation of the existing double bonds in the C22-C23 position of avermectin B
1
macrolid structures leads to the synthesis of ivermectin as described in literature.
Ivermectin, a macrocyclic lactone, whose developed formula is:
where R2 is isopropyl (20%) or sec-butyl (80%), is a broad spectrum antiparasitic not only against internal parasites, but also against external parasites and even endoparasitic stages of several arthropods. It is active against nemathod genera which affect pets and cattle such as Trichostrongyloidea, Strongyloidea, Metastrongyloidea, Rhabditoidea, Ascaridoidea, Oxyuroidea, Spiruroidea, Filaroidea and Trichurioidea superfamilies. Its high solubility, high body penetration and long term average life, account for the broad use of ivermectin as antihelminthic.
The normal way to administer antiparasiticides to large animals is orally. Patents EP 473223, EP 537000, EP 537998 and U.S. Pat. No. 4,440,740 describe solid formulations of ivermectin.
Highly efficient injectable formulations have also been described and their handy application triggered the appearance of a series of preparations, such as the ones described in the following patents which are related with liquid administration forms: EP 146414, EP 413538, EP 535734, EP 538750 and U.S. Pat No. 4,389,397.
More specifically, patent EP 146414, protects certain non watery liquid formulations which contain ivermectin and more precisely, those which contain ivermectin 1% in a vehicle formed by a mixture of 40% formal glycerol—60% propylene glycol.
The object of the present invention is a novel injectable, long acting parasiticidal composition which contains ivermectin and which presents comparatively superior pharmakinetic properties over known formulations.
Said novel, long acting, injectable parasiticidal composition presents acceptable levels of residue for the consumption of beef by humans, in conditions of total safety. The European Union has settled maximum residue quantities for ivermectin in bovines at 100 ug/kg in liver and 40 ug/kg in fat.
Likewise, the object of the present invention is a process for the preparation of said novel injectable, long acting parasiticidal composition.
Therefore, the object of the present invention is an injectable, long acting parasiticidal composition which comprises enough ivermectin to achieve a final concentration of about 1% (w/w), benzilic alcohol, polyvinylpyrrolidone, N-methyl-2-pyrrolidone in a 40-65% proportion (v/w) of the total formulation and glycerin until completing final 100% weight.
Besides these components, the formulation may contain stabilizers/antioxidants such as thiodipropionic acid, acetyl cysteine, cysteine, sodium metabisulfite, EDTA, sodium EDTA, sodium citrate, N-propyl gallate, butyl-hydroxy-toluene or a mixture of more than one of these products in a 0.01 to 2% w/w proportion. Optionally, the formulation may also contain a coloring such as betacarotene, in a 0.005-0.05 w/w proportion.
Another object of the present invention is the procedure to prepare an injectable, long acting parasiticidal composition which involves mixing enough ivermectin to obtain a final concentration of about 1% (w/w) with benzilic alcohol and polyvinylpyrrolidone followed by the addition of the mixture to N-methyl-2-pyrrolidone, the latter in a 40-65% proportion (v/w) of the total of the formulation. Afterwards, the antioxidant or mixture of antioxidants dissolved in water if necessary, are added. The mixture is shaken until totally dissolved and glycerin is added until reaching 100% final weight.
Polyvinylpyrrolidone that has been used in the composition of the invention is Kollidon K 17 PF with a K 16-18 value and a relative viscosity of the solution in distilled water at 5% from 1.250-1.370. Kollidon K 17 PF is preferably used in a proportion between 7-11% (w/w) of the total of the mixture.
Benzilic alcohol is incorporated to the mixture in an appropriate proportion to achieve a final concentration between 1.5 and 2% (w/w).
REFERENCES:
patent: 413538 (1991-08-01), None
patent: 9505812 (1995-03-01), None
Biogenesis S.A.
Birch Stewart Kolasch & Birch, LLP.
Levy Neil S.
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