RU2251421C2 - Antiparasitic preparation for needle-free injection - Google Patents

Abstract

FIELD: veterinary science.

SUBSTANCE: the suggested preparation is being the solution of either avermectines or their derivatives in organic solvents or their mixtures at concentration of 1-35 g/100 ml; as organic solvents the preparation contains benzyl alcohol, ethanol, triethylene glycol, dimethylsulfoxide or their mixtures. This preparation provides in case of needle-free injection the development of "depot" of active substance. Moreover, the latter practically does not enter milk, so the preparation could be applied for treating lactating cows.

EFFECT: higher efficiency of needle-free injection technique.

1 cl, 2 dwg, 3 tbl

Description

The invention relates to the field of veterinary medicine and can be used for the prevention and treatment of diseases caused by parasites of animals, in particular agricultural.

The effectiveness of antiparasitic treatment of livestock in large livestock farms depends on a number of factors: the active ingredient used, the composition of the preparation containing the active substance, the route of administration of the drug to animals, etc. The route of administration of the drug largely determines the requirements for its composition, which should provide an acceptable combination the solubility of the active substance, bioavailability, viscosity and stability of the drug, a minimum of adverse reactions, etc.

The most common subcutaneous and intramuscular routes of administration of antiparasitic drugs using syringes. Less commonly used are formulations for oral administration or topical topical application (US Pat. No. 5773422, 1996). Among the active substances of antiparasitic drugs, avermectins and their derivatives (individual or in complexes) occupy a significant place, including in combination with other substances. The most common avermectin B ₁ -abamectin and its dihydro derivative ivermectin, as well as mixtures (complexes) of individual avermectins - aversectin C and aversectin AB. The most commonly used solvent for water-insoluble avermectins is polyethylene glycol or propylene glycol. Known drugs for the control of animal parasites, the active substance of which is a complex of avermectins, called ivermectin (patent EP 146414, 1985), or closantelum mixed with avermectins (patent RU 2129430, 1999). The disadvantage of such drugs is a severe pain and inflammatory reaction in animals with both intramuscular and subcutaneous administration of drugs.

Known injection drug containing avermectin solution in hydrogenated castor oil and retaining activity for about 40 days (patent EP 535734, 1993). In this case, the drug does not cause severe pain and irritation in animals.

But with sufficient effectiveness of injectable drugs administered by conventional syringes, the process of processing animals is very time-consuming.

Known antiparasitic agent based on avermectins, applied in the form of an aerosol to the mucous membrane of animals (patent CN 1176100, 1998). The bioavailability of the agent is 90% and ensures the death of nematodes at the level of 95% of the agent for intramuscular administration. But even with this method of processing, the complexity of the process decreases not very significantly.

The proposed drugs based on avermectins or their derivatives, the composition of which allows animals to be injected intradermally using the needleless injector, provides a sharp decrease in the complexity of antiparasitic treatment while maintaining efficacy at the level of drugs administered intramuscularly. Empirically, the concentrations of abamectin, ivermectin, aversectin C and aversectin AB in organic solvents are acceptable for injection by injection method. They are in the range of 1-35 g / 100 cm ³ (1-35 g / 100 ml). Preferred solvents for preparing solutions of antiparasitic drugs are benzyl alcohol, ethyl alcohol, triethylene glycol, dimethyl sulfoxide, or mixtures thereof: 95% benzyl alcohol and 5% ethyl alcohol; 80% triethylene glycol and 20% ethyl alcohol; 50% benzyl alcohol and 50% dimethyl sulfoxide and others.

For cattle (cattle), the preparations according to the invention are used against nematodoses (strongilatoses, trichocephaliasis, strongyloidoses) and ectoparasites (psoroptosis, sarnoptosis, chornoptosis, sifunculosis) and with hypodermatosis at a dose of 0.2 mg / kg of animal weight (0.4 mg / kg kg animal weight for aversectin AB).

For pigs, it is used in case of nematodoses (metastrongylosis, ascariasis, esophagostomiasis, strongyloidosis) and against ectoparasites (sarcoptosis, hematopinosis) at a dose of 0.3 mg / kg of animal weight (0.6 mg / kg of animal weight for aversectin AB).

Example 1

10 g of abamectin was dissolved in 80 cm ^{3 of} benzyl alcohol in a volumetric flask with a capacity of 100 cm ³ when heated in a water bath at a temperature of 50-60 ° C. After cooling, the volume was adjusted to 100 cm ³ and mixed thoroughly.

Example 2

20 g of ivermectin was dissolved in 70 cm ^{3 of} benzyl alcohol in a volumetric flask with a capacity of 100 cm ³ when heated in a water bath at a temperature of 50-60 ° C. After cooling, the volume was adjusted to 100 cm ³ and mixed thoroughly.

With the same amount of ivermectin, solutions were prepared in dimethyl sulfoxide or a mixture of 50% benzyl alcohol and 50% dimethyl sulfoxide, etc.

Example 3

20 g of aversectin C was dissolved in 70 cm ^{3 of} benzyl alcohol in a volumetric flask with a capacity of 100 cm ³ when heated in a water bath at a temperature of 50-60 ° C. After cooling, the volume was adjusted to 100 cm ³ and mixed thoroughly.

With the same amount of aversectin C, solutions were prepared in a mixture of 95% benzyl alcohol and 5% ethyl alcohol, etc.

Example 4

35 g of aversectin AB was dissolved in 60 cm ^{3 of} benzyl alcohol in a 100 cm volumetric flask when heated in a water bath at a temperature of 50-60 ° C. After cooling, the volume was adjusted to 100 cm and mixed thoroughly.

With the same amount of aversectin AB, solutions were prepared in triethylene glycol or a mixture of 80% triethylene glycol and 20% ethyl alcohol, etc.

The test results of antiparasitic drugs are given in the following examples.

Example 5

In the experiment, 25 cows were used spontaneously infected with strongilates of the gastrointestinal tract and dictiocaul. Formed 5 groups of animals. The first group was injected with a 10% solution of abamectin, the second group with a 20% solution of ivermectin, the third group with a 20% solution of aversectin C, the fourth group with a 35% solution of aversectin AB, and the fifth group served as a control. The drug was injected intradermally by the injection method using a needleless injector in a dose of 0.4 ml (two shots). Cows from the control group were not exposed to treatment.

The effectiveness of the preparations was determined by the results of helminthovirus and larvoscopy of fecal samples from experimental animals before treatment and 14 days after treatment. The results are presented in table 1.

Table 1 Drug, No. of animal group Helminth eggs and larvae detected Strongilat Dictiocaul Before treatment After treatment Before treatment After treatment 10% r-abamectin, group No. 1 II ex-82.3 ± 28.7
EI% -100 0
0 EI% -100 0 20% ivermectin solution, group No. 2 II ex-85.9 ± 30.5
EI% -100 0
0 EI% -100 0 20% aversectin C solution, group No. 3 II ex-93.7 ± 28.2
EI% -100 0
0 EI% -100 0 35% solution of aversectin AB, group No. 4 II ex-87.3 ± 39.8
EI% -100 0
0 EI% -100 0 Control, Group No. 5 II ex-85.4 ± 29.7
EI% -100 II ex-86.8 ± 27.3
EI% -100 EI% -100 EI% -100

Example 6

In a cattle hypodermatosis-dysfunctional disease, 20 cows were selected. The animals were divided into 2 groups - experimental and control, ten animals each.

In the autumn, after the end of the summer of flying gadfly, the cows of the experimental group were injected intracutaneously with a 20% solution of aversectin C with the injection method using a needleless injector in a dose of 0.4 ml (two shots) intracutaneously. Cows from the control group were not exposed to treatment.

A commission examination of all animals with the identification and counting of all formed in the area of the croup and partly the sides of the gadfly chews was carried out after six months. In the experimental group, in two animals, infection with bovine gadfly larvae with an average intensity of 1.5 specimens per infected animal or 0.3 specimens of all animals of this group was detected, while in the cows of the control group 100% extensinvasion was recorded with an average intensity of 10.1 specimens per the cow. The extensibility (EE) of the intradermal injection of a 20% injection of aversectin C during bovine bovine infestation was equal to 80.0%, and the intensification (IE) was 97.0%.

In the specified dose, the drug does not cause any significant swelling at the injection site, an increase in the local temperature reaction and pain.

Example 7

In the experiment, 35 piglets were used at the age of 3-4 months with a weight of 40-45 kg, spontaneously infected with roundworms and lice. Formed 3 groups of animals. Two groups of 15 animals, the third in the amount of 5 piglets served as a control. In the first group, a 10% solution of abamectin was used, in the second group, 20% of ivermectin. The drug was injected intradermally by injection using a needleless injector at a dose of 0.3 mg / kg. Piglets from the control group were not exposed to treatment. The effectiveness of the preparations was determined by the results of a clinical examination and detection of lice and nits on the body and hairline of animals. Nematodicidal efficacy was evaluated according to the results of helminthovoscopy of animal feces samples from experimental and control animals before treatment and 14 days after drug administration. The results are shown in table 2.

table 2 Drug group Animal invasion Efficiency (%) lice roundworm (ind.) against lice against roundworms 10% abamectin solution, group No. 1 +++ 150 ± 16.3 100 100 20% ivermectin solution, group No. 2 +++ 169 ± 11.5 100 100 Control, group No. 3 +++ 161.3 ± 17.5 - -

Example 8

In the experiment, 12 lactating cows were used, of which 4 groups were formed.

The first group was injected with a 20% ivermectin solution.

The second group - 20% solution of aversectin C.

The third group - 35% solution of aversectin AB.

The solutions were administered at a dose of 0.4 ml per animal (80 mg of active ingredient) using a needleless injector.

The fourth group was used as a control. Animals of this group were injected with a 1% solution of aversectin C (aversect-2) at a dose of 8 cm ³ (80 mg of active substance).

12 hours after the administration of preparations to animals, and then on 1, 2, 3, 4, 5, 7, 10, 14, and 21 days milk samples were taken in which the content of avermectins was determined. Determination of the content of avermectins in milk was performed by fluorescence high performance liquid chromatography. The results of the determination of the content of avermectins (ng / cm ³ ) are shown in table 3 and figure 1.

Example 9

Aversectin C 20% was administered once to 15 calves weighing 100-110 kg at the rate of 0.1 ml per 100 kg of body weight (which corresponds to a dose of 0.2 mg / kg for the active substance per kg of body weight). The drug was administered with a needleless injector.

Three calves were killed after 12 hours; 1; 5; 10 and 15 days after administration of the drug. Muscle and liver samples were taken from all animals. Samples were analyzed for avermectins. The analysis was performed by fluorescence high performance liquid chromatography.

The results of the analysis are shown in figure 2.

The results of testing the effectiveness of the concentrated forms of avermectin-containing antiparasitic preparations according to the invention showed that, in their behavior in the animal’s body, the concentrated forms differ from the previously known ones in that they practically do not stand out with milk and accumulate in the organs and tissues of the animal in amounts below the permitted level. These circumstances make it possible, firstly, to use concentrated forms of avermectin-containing preparations in the dairy herd, and secondly, to reduce the waiting time for the use of meat products after using concentrated forms by 10-15 days compared with the known forms.

Claims (2)

1. An antiparasitic drug for needleless administration in the treatment of farm animals, which is a solution of avermectins or their derivatives in organic solvents or their mixtures at a concentration of 2-35 g / 100 ml. 2. The antiparasitic preparation according to claim 1, characterized in that, as organic solvents, the preparation contains benzyl alcohol, ethyl alcohol, triethylene glycol, dimethyl sulfoxide or mixtures thereof.

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