CN1069032C - Antiparasitic medicine containing avermectin/ivermectin for animals - Google Patents

Abstract

The present invention is a kind of veterinary antiparasitic medicine containing abamectin (AVM) or ivermectin (IVM), and it is characterized in that it is prepared into the colloidal suspension containing 0.05-10% AVM/IVM, emulsion and It is mixed with anthelmintics such as levamisole and albendazole to form a compound preparation. The invention contains AVM/IVM veterinary antiparasitic medicine, has low production cost, simple production process, convenient use and relatively good effect.

Description

A kind of veterinary antiparasitic drug containing avermectin/ivermectin

The invention belongs to veterinary antiparasitic drugs, more precisely, the present invention is a veterinary antiparasitic drug of Avermectin B ₁ (abbreviated as AVM) or its derivative ivermectin (abbreviated as IVM). Parasite gel suspensions, suspensions and creams.

In the 1980s, American MERCK Company successfully developed AVM or IVM into veterinary antiparasitic drugs, but at present there are dosage forms of powder, injection, capsule and smear, and these dosage forms all have certain shortcomings, such as powder in the production process. There is dust pollution, which affects the health of operators, and the amount of smears is relatively large, making it inconvenient to use powders, capsules, and injections.

The purpose of the present invention is to overcome some shortcomings of the prior art, to provide a low production cost, high drug efficacy containing IVM or AVM veterinary anti-parasitic gel suspension, emulsion and emulsifiable paste.

The colloidal suspension of the present invention is made of AVM, wetting agent, dispersion suspending agent, antifreeze, preservative, dispersion medium, and its component content (taking colloidal suspension weight as 100%): IVM or AVM 0.5-10%, wetting agent 0.2-10%, dispersion suspending agent 0.2-30%, antifreeze agent 5-15%, preservative 0.1-1%, and the rest is dispersion medium.

The preparation method of the colloidal suspension adopts the usual preparation technology to mix AVM or IVM with a wetting agent and a dispersion medium, homogenize and grind to 20-80 microns with a colloid mill, and then grind to 0.25 microns by a sand mill , add dispersing suspending agent, antifreeze, preservative, and homogenize with a high-speed shear emulsifying disperser to obtain a colloidal suspension.

The composition and content of the emulsion of the present invention (taking the weight of the emulsion as 100%): AVM or IVM0.05～10%, organic solvent 2～80%, emulsifier 1～30%, tackifier 0.2～10% %, antifreeze 5-10%, preservative 0.1-1%, and the rest is water.

The preparation method of the emulsion adopts the usual preparation technology, that is, the AVM or IVM is dissolved in an organic solvent, an emulsifier is added, a stabilizer, an antifreeze, a preservative and water are mixed, and homogenized by a high-speed shearing disperser to obtain emulsion.

The composition and content of the cream of the present invention (taking the cream weight as 100%): AVM or IVM 0.05～10%, organic solvent 2～80%, emulsifier 1～30%, tackifier 0.5～30% %, antifreeze 5-15%, preservative 0.1-1%, and the rest is water.

The preparation method of the cream is the same as that of the emulsion, except that more viscosifiers are added to form a paste or cream that is difficult to flow.

The AVM of the present invention is a metabolite of Streptomyces avermitilis, consisting of eight structures, namely A _1a , A _1b , A _2a , A _2b , B _1a , B _1b , B _2a , B _2b , Composed of homologues, B _1a component has the highest insecticidal activity and the broadest insecticidal spectrum, but B _1b and B _1a have very similar structures and are difficult to separate, so they are usually a mixture of the two, referred to as AVM. The IVM (Ivermectin) is a derivative of AVM William C. Campbell, "Ivermectin ana Abamectin", Springer-verlag New York Inc. 1989, P1-23.

The AVM or IVM can also be made into an oily liquid to replace the crystalline product (or called the original drug) of the AVM or IVM with a purity of about 90%. The preparation method of the oily liquid: the strains used for production are fermented and filtered for 7 to 9 days to obtain the mycelium, the mycelium is extracted with acetone, ethanol or other organic solvents, filtered, the extract is recovered, decolorized and the toxic components are removed , concentrated under reduced pressure to an oil paste, the paste mixture contains Averimectin A ₁ 3-10%, A ₂ 8-25%, B ₁ , 6-25%, B ₂ 3-10%, lipid 10-30% , Water 5-10%.

Described wetting agent comprises Tween-80, sodium lauryl sulfate, sodium dodecylbenzenesulfonate; Described dispersion suspending agent comprises xanthan gum, gum arabic, methylcellulose, carboxymethyl Base cellulose; Described antifreeze comprises ethylene glycol, propylene glycol; Described emulsifier comprises Tween-80, OP-10, OP-21; Described preservative comprises sodium benzoate, sodium salicylate, benzene Methanol; described organic solvent comprises ethyl acetate, acetone, ethanol; described dispersion medium comprises water, animal and vegetable oil.

The above-mentioned suspensions, emulsions and creams can be compounded by adding other known anthelmintic drugs. Square gel suspension, compound emulsion and compound cream. The other anthelmintic drugs mentioned include levamisole and albendazole, added in an amount of 1 to 20% of the weight of the compound preparation, and its addition method: mixing with other components in the preparation of a single dose, or adding to the prepared single dose in, and mix well.

The gel suspension, emulsion, cream or its compound preparation of the present invention can be used for deworming cattle and sheep, including internal nematodes, external mites, ticks, lice, fly maggots and other parasites. When using a suspension, emulsion or cream compound, after diluting with water, use 0.2 mg of AVM (or IVM) per kilogram of body weight for oral gavage.

The veterinary anti-parasitic preparation containing AVM or IVM proposed by the present invention overcomes the shortcomings of the existing preparations, and the production cost is reduced due to the use of less or no organic solvents, and the production process is simple, and there is no dust pollution in the production process. It is simple and convenient to use, and the effect is relatively good.

Further describe characteristics of the present invention with example below:

Example 1

This example is to prepare the colloidal suspension containing AVM 0.1%.

Grind 0.55Kg of the original drug of AVM (purity 90%) to below 300 microns, mix it with 1 kg of sodium lauryl sulfate and 2 kg of distilled water, grind it to 20-80 microns with a colloid mill, and then grind it to 0.2 microns with a sand mill. ~5 microns, add 1% carboxymethylcellulose solution, 5% propylene glycol, and 1% sodium benzoate to a total volume of 500 liters, and homogenize to obtain the required suspension.

Example 2

In this example, the oily liquid of AVM is used to prepare a suspension containing 0.2%.

Take 2kg of oily liquid with 10% AVM content, add 4 liters of Tween-80 and homogenize it with a high shear emulsifier at 50°C, add 10 liters of 1,2-propanediol and mix, then add 0.3% xanthan gum solution To 100 liters, grind in a sand mill until the solid particles are below 0.2 microns.

Example 3

This example is to prepare the colloidal suspension containing AVM 10%.

Grind 55kg of AVM (purity 90%) technical material to below 300 microns, mix with 40kg of Tween 080, 100kg of distilled water, use a colloid mill to homogenize and grind to about 20-80 microns, and use a sand mill to grind to a fineness of 0.2 -5 microns, add 75kg 1,2 propylene glycol, 0.5kg sodium benzoate, and then add 10% carboxymethyl cellulose solution to 500 liters.

Example 4

In this example an emulsion was prepared containing 0.2% AVM.

After dissolving AVM 1.1Kg with a purity of 90% in 10 liters of acetone, add 20 liters of Tween-80, mix until homogeneous at high speed, then add a stabilizing solution (containing 8% methylcellulose, 1,2-propanediol 15%, benzyl alcohol 1%, and the rest is water) to 500 liters, and homogenize to obtain the emulsion.

Example 5

This example is to prepare an emulsion containing 10% AVM

Preparation process is the same as example 3. The content of each component: AVM (content 90%) 11Kg ethanol 50 liters, Tween-80 30 liters, add stabilizing solution (containing xanthan gum 0.2%, 1,2-propylene glycol 5%, sodium benzoate 0.2%, the rest is water ) to 100 liters, homogenized to obtain the emulsion.

Example 6

This example is the preparation of a cream containing 0.2% AVM.

Dissolve 1.1 kg of AVM with a purity of 90% in 10 liters of ethyl acetate, add OP-1040 liters, homogenize with an emulsifier, add 75 liters of 1,2-propanediol, 1 kg of sodium salicylate, and then add 1% gum arabic liquid to 500 liters, and obtain the required cream through homogenization.

Example 7

This example is the preparation of cream containing 10% IVM.

Preparation process is with example 5. The content of components used: 11kg of IVM with a purity of 90%, 60 liters of acetone, 20 liters of Tween-80, 5 liters of 1,2-propanediol, after homogenization, add a viscosifier (containing 0.9% xanthan gum, benzene Sodium formate 0.2%, the rest is water) to 100 liters and finally get the emulsifiable cream through homogenization.

Example 8

This example is to prepare the compound suspension containing 0.2% AVM-6% albendazole.

Take 0.22 kg of AVM with a purity of 90%, add 6 kg of albendazole, 5 liters of 1,2-propanediol, 1 kg of sodium benzoate, and 2 liters of Tween-80, grind it in a sand mill, and add 0.15% of Xanthan gum solution to 100 liters, further grinding to homogenization.

Example 9

This example is to prepare the compound cream containing 5% IVM-18% levamisole.

After 5.5Kg of IVM with a purity of 90% was dissolved in 10 liters of ethanol, 5 liters of Tween-80 was added, mixed evenly and then 18 kg of levamisole was added. Mix 5 liters of 1,2-propylene glycol and grind until the solid phase particles are 0.2 to 4 microns, then add 55.5 liters of 0.6% xanthan gum solution and 1 liter of 10% sodium benzoate solution, stir and shear until homogenized to obtain the compound emulsion.

Example 10

This solid side is to prepare the compound cream containing 5% AVM-18% albendazole with AVM oily liquid.

Take 20kg of oily liquid with an AVM content of 25%, add 18kg of albendazole, 20 liters of Tween-80, and 5 liters of 1,2-propylene glycol, grind it with a sand mill until the solid phase particles are 0.2-2 microns, add 0.8% xanthan Glue to 100 liters, further grinding until homogeneous to obtain the desired product.

Example 11

This example is the preparation of the present invention and AVM-containing powder, capsule comparison. The results are shown in Table 1 and Table 2.

Table 1 Comparison table of the reduction rate of various dosage forms of AVM to various types of nematode eggs (larvae) in sheep dosage form Dose (mg/kg) Egg (larvae) reduction rate Trichosanthes austenis tenornis Dictyocaulus Prostrongylus nematodes nematodes nematodes (larvae) larvae (larvae) Example 2 Colloidal Suspension Example 4 Emulsion Example 6 Ointment 0.2% AVM Injection * AVM Powder ** AVM Capsule *** 0.20.20.20.20.20.2 100 98.7 100 100 95.0100 98.5 100 100 93.5100 98.5 100 100 93.7100 98.3 100 100 93.598.5 97.7 100 98.2 90.397.6 97.2 100 95.0 *AVM injection is the new veterinary drug certificate No. 23 of the Ministry of Pesticides of the People's Republic of China (94); **VM powder is the new veterinary drug certificate of the Ministry of Pesticides of the People's Republic of China (94) New Veterinary Drug Certificate No. 24; ***AVM The capsules are self-made, formula: AVM0.2%, the rest is CaCO ₃ .

Table 2: Example 8 compound gel suspension and AVM albendazole single dose comparison table for the deworming rate of sheep endoparasites project Compound albendazole single agent AVM single dose AVM (mg/kg) albendazole (mg/kg) 0.26 -6 0.2- Trichostrongylus Osteria worm 10010098.710010099.2 98.397.698.010097.298.5 98.799.298.310098.099.2 Monitz tapeworm (adult) 100 100 0 yolkless tapeworm 100 97.3 0

Claims (4)

1. A kind of veterinary antiparasitic medicine containing abamectin or ivermectin, it is characterized in that it is made of abamectin or ivermectin and wetting agent, dispersion suspending agent, antifreezing agent, preservative 1. The colloidal suspension composed of dispersion medium, its composition content (calculated as colloidal suspension 100%) is: avermectin or ivermectin 0.05-10%, wetting agent 0.2-10%, dispersing suspending agent 0.1% -5%, antifreeze 5-15%, preservative 0.1-1%, and the rest is dispersion medium. The wetting agent includes Tween-80, sodium lauryl sulfate, sodium dodecylphenyliodate , described dispersion suspending agent comprises xanthan gum, gum arabic, methyl cellulose, carboxymethyl cellulose, described antifreeze comprises ethylene glycol, propylene glycol, glycerine, and described preservative comprises sodium benzoate, Sodium salicylate, benzyl alcohol, and the described dispersion medium includes water, animal oil, vegetable oil. 2. A veterinary antiparasitic drug containing abamectin or ivermectin, characterized in that it is composed of avermectin or ivermectin and organic solvent, wetting agent, emulsifier, viscosifier, An emulsion composed of antifreeze, preservative, and water, whose composition content (based on 100% of the emulsion) is: 0.05-3% of avermectin or ivermectin, 2-80% of organic solvent, and 1-30% of emulsifier , thickening agent 0.1-5%, antifreeze agent 5-10%, preservative 0.1-1%, the rest is water, described organic solvent includes ethanol, propanol, ethyl acetate, and described emulsifier includes Tween -80, OP-10, OP-21, described thickening agent comprises xanthan gum, gum arabic, methylcellulose, carboxymethylcellulose, described antifreeze comprises ethylene glycol, propylene glycol, glycerin, Described antiseptic comprises sodium benzoate, sodium salicylate, benzyl alcohol. 3. According to the antiparasitic drug described in claim 1, it is characterized in that the anthelmintic that comprises levamisole and albendazole can be mixed in the described gel suspension to make a compound gel suspension, and the anthelmintic The addition amount is 1-20% of compound gel suspension weight. 4. According to the antiparasitic drug described in claim 2, it is characterized in that the anthelmintic that comprises levamisole and albendazole can be mixed in the described emulsion to make a compound emulsion, and the addition of the described anthelmintic is 1-20% of compound emulsion weight.