KR20000004995A - Pesticide for parasitic insects and acarids on humans - Google Patents

Abstract

PURPOSE: The pesticide for parasitic insects and acarids on human is provided, which comprises agonists or antagonists of the nicotinic acetylcholine receptors of insects. CONSTITUTION: In relation to the total weight of the composition, agonists or antagonist of the nicotinic acetylcholine receptors of insects in a concentration of 0.0001 to 20 wt.% are mixed with a solvent from the group of cyclic carbonates in a concentration of 2.5 to 99.9999 wt.%. Other solvents such as alcohols are added in a concentration of 0 to 95 wt.%, and other auxiliary agents such as thickeners, spreading agents, and colourants can be added in a concentration of 0 to 30 wt.%.

Description

Composition for parasitic insect and tick control for humans

Agonists or antagonists of nicotinic acetylcholine receptors in insects are known. These include nicotinyl insecticides and very particularly chloronicotinyl insecticides.

PCT application WO 93/24002 discloses certain 1- [N- (halo-3-pyridylmethyl)]-N-methylamino-1-alkylamino-2-nitroethylene derivatives for systemic use against livestock fleas. It is disclosed as appropriate. According to WO 93/24 002, the non-systemic application mode-that is, the skin application mode is inadequate for controlling livestock fleas.

The present invention relates to agents for controlling parasitic insects and ticks on the skin of humans by agonists or antagonists of nicotinergic acetylcholine receptors of insects.

The present invention provides a novel formulation for skin application of an agonist or antagonist of nicotine-effective acetylcholine receptors of insects which is particularly suitable for the dermal relief of parasitic insects and ticks on humans.

The formulations according to the invention have the following composition:

-Agonists or antagonists of nicotinic potency acetylcholine receptors in insects at concentrations from 0.0001 to 20% by weight, based on the total weight of the preparation;

Solvent from cyclic carbonate groups at a concentration of 2.5 to 99.9999% by weight, based on the total weight of the formulation;

If desired, additional solvent from an alcohol group at a concentration of 0 to 95% by weight, based on the total weight of the formulation;

If desired, an additional adjuvant selected from the group consisting of thickening agents, spreading agents, coloring agents, antioxidants, propellants, preservatives, adhesives, emulsifiers at concentrations of 0 to 30% by weight, based on the total weight of the preparation.

Agonists or antagonists of nicotinic acetylcholine receptors in insects are described, for example, in EP 580 553, 464 830, 428 941, 425 978, 386 565, 383 091, 375 907, 364 884 No. 315 826, 259 738, 254 859, 235 725, 212 600, 192 060, 163 855, 154 178, 136 636, 303 570, 302 833, 306 696, 189 972, 455 000, 135 956, 471 372, 302 389; German Publication Nos. 3 639 877, 3 712 307; Japanese Patent Application Laid-Open No. 03 220 176, 02 207 083, 63 307 857, 63 287 764, 03 246 283, 04 9371, 03 279 359, 03 255 072; U.S. Patent Specifications 5 034 524, 4 948 798, 4 918 086, 5 039 686, 5 034 404; PCT Applications WO 91/17 659, 91/4965; French application 2 611 114; Known from Brazilian application 88 03 621.

The compounds and their preparation described in these publications are expressly incorporated herein by reference.

These compounds can advantageously be represented by general formula (I):

Where

R represents hydrogen or an optionally substituted radical selected from the group consisting of acyl, alkyl, aryl, aralkyl, heteroaryl and heteroarylalkyl;

A represents a monofunctional group selected from the group consisting of hydrogen, acyl, alkyl and aryl, or a bifunctional group linked to the radical Z;

E represents an electron-drawing radical;

X represents the radical -CH = or = N-, and it is possible for the radical -CH = to be connected to the radical Z in place of the H atom,

Z is alkyl, -OR, -SR and It represents a monofunctional group selected from the group consisting of or a bifunctional group linked to radical A or radical X.

Particularly preferred compounds of formula (I) are those in which the radicals have the following meanings:

R represents hydrogen or an optionally substituted radical selected from the group consisting of acyl, alkyl, aryl, aralkyl, heteroaryl and heteroarylalkyl.

Acyl radicals that may be mentioned are formyl, alkylcarbonyl, arylcarbonyl, alkylsulfonyl, arylsulfonyl, (alkyl)-(aryl) -phosphoryl, which may be substituted again.

Alkyl which may be mentioned is C _1-10 -alkyl, in particular C _1-4 -alkyl, in particular methyl, ethyl, i-propyl, secondary- or tert-butyl, which may in turn be substituted.

Aryl that may be mentioned is phenyl, naphthyl, in particular phenyl.

Aralkyls which may be mentioned are phenylmethyl, phenethyl.

Heteroaryls which may be mentioned are heteroaryls having up to 10 reducers and N, O, S, in particular N atoms, as heteroatoms. In particular, mention may be made of thienyl, furyl, thiazolyl, imidazolyl, pyridyl, benzothiazolyl.

Heteroarylalkyl which may be mentioned are heteroarylmethyl with up to 6 reducing and heteroatoms N, O, S, in particular N, heteroarylethyl.

Substituents which may be listed by way of example and as preference are preferably alkyl having 1 to 4, especially 1 or 2 carbon atoms, for example methyl, ethyl, n- and i-propyl and n-, i- and t-butyl; Preferably alkoxy having 1 to 4, especially 1 or 2 carbon atoms, for example methoxy, ethoxy, n- and i-propyloxy, and n-, i-, t-butyloxy; Preferably alkylthio having 1 to 4, especially 1 or 2 carbon atoms, for example methylthio, ethylthio, n- and i-propylthio and n-, i- and t-butylthio; Preferably having 1 to 4, in particular 1 or 2 carbon atoms and preferably 1 to 5, especially 1 to 3 halogen atoms, the halogen atoms being the same or different, preferably fluorine, chlorine, or Bromine, especially halogenoalkyl which is fluorine such as trifluoromethyl; Hydroxyl; Halogen, preferably fluorine, chlorine, bromine and iodine, in particular fluorine, chlorine and bromine; Cyano; Nitro; Amino; Preferably monoalkyl- and dialkylamino having 1 to 4, in particular 1 or 2 carbon atoms per alkyl group, for example methylamino, methyl-ethyl-amino, n- and i-propylamino and methyl-n- Butylamino; Carboxyl; Preferably carboalkoxy having 2 to 4, especially 2 or 3 carbon atoms, for example carbomethoxy and carboethoxy; Sulfo (-SO ₃ H); Preferably alkylsulfonyl having 1 to 4, especially 1 or 2 carbon atoms, for example methylsulfonyl and ethylsulfonyl; Preferably arylsulfonyl having 6 or 10 aryl carbon atoms, for example phenylsulfonyl, and also heteroarylamino and heteroarylalkylamino, for example chloropyridylamino and chloropyridylmethylamino.

A particularly preferably represents hydrogen, or preferably an optionally substituted radical selected from the group consisting of acyl, alkyl and aryl having the meaning defined for R. A also represents a bifunctional group. It may be mentioned optionally substituted alkylene having 1 to 4, in particular 1 or 2 carbon atoms, substituents which may be mentioned are substituents listed above and the alkylene group is a group consisting of N, O, S It is possible to be blocked by a heteroatom selected from.

A and Z together with the atoms to which they are attached form a saturated or unsaturated heterocyclic ring. Heterocyclic rings may further contain one or two identical or different hetero atoms and / or hetero groups. The heteroatom is preferably oxygen, sulfur or nitrogen, the heterogroup is preferably N-alkyl, wherein the alkyl in the N-alkyl group preferably contains 1 to 4, in particular 1 or 2 carbon atoms do. Alkyl which may be mentioned are methyl, ethyl, n- and i-propyl and n-, i- and t-butyl. Heterocyclic rings contain 5 to 7, preferably 5 or 6 reductions.

Examples of heterocyclic rings that may be mentioned are imidazolidine, pyrrolidine, piperidine, piperazine, hexamethyleneimine, hexahydro-1,3,5-triazine, hexahydrooxodiazine, morpholine Each of which may be optionally substituted by methyl, preferably.

E represents an electron-drawing radical, which may in particular be mentioned in this connection are NO ₂ , CN, halogenoalkylcarbonyl, for example 1,5-halogeno-C _1-4 -carbonyl, in particular COCF ₃ to be.

X represents -CH = or -N =.

Z represents optionally substituted radical alkyl, -OR, -SR, -NRR, wherein R and substituents preferably have the above-mentioned meanings.

Z is a radical with and instead of X the atom to which it is attached, apart from the aforementioned ring Together with a saturated or unsaturated heterocyclic ring can be formed. Heterocyclic rings may further contain one or two identical or different heteroatoms and / or groups. The heteroatom is preferably oxygen, sulfur or nitrogen, the heterogroup is preferably N-alkyl, in which case the alkyl or N-alkyl group preferably contains 1 to 4, in particular 1 or 2 carbon atoms. . Alkyl which may be mentioned are methyl, ethyl, n- and i-propyl and n-, i- and t-butyl. Heterocyclic rings contain 5 to 7, preferably 5 or 6 reductions.

Examples of heterocyclic rings that may be mentioned are pyrrolidine, piperidine, piperazine, hexamethyleneimine, morpholine and N-methylpiperazine.

As compounds which can be used very particularly preferably according to the invention, those which may be mentioned are compounds of the general formulas (II) and (III):

Where

n represents 1 or 2,

Subst. Represents one of the substituents listed above, in particular halogen, very particularly chlorine,

A, Z, X and E have the meanings defined above.

In particular, the following compounds may be mentioned:

The preparations according to the invention contain the active substance at a concentration of 0.0001 to 20% by weight, preferably 0.1 to 12.5% by weight, particularly preferably 1 to 10% by weight.

Formulations diluted prior to use contain the active substance at a concentration of 0.5 to 90% by weight, preferably 1 to 50% by weight.

Suitable solvents are water, cyclic carbonates. Preferred cyclic carbonates are ethylene carbonate, propylene carbonate. Especially preferred is propylene carbonate.

They are present at concentrations of 2.5 to 99.9999% by weight, preferably 7.5 to 90% by weight, particularly preferably 10 to 90% by weight.

Suitable further solvents are cyclic and acyclic alcohols such as isopropanol, ethanol, diethylene glycol, 2-octyl-1-dodecanol and tetrahydrofuryl alcohol.

They are present at concentrations of at least 0 to 95% by weight, preferably 5 to 30% by weight, particularly preferably 5 to 20% by weight.

Suitable further auxiliaries are preservatives such as benzyl alcohol (not required if already present as a solvent), trichlorobutanol, p-hydroxybenzoic acid esters, n-butanol and solubility enhancers.

They are present at concentrations of 0 to 15% by weight, preferably 2.5 to 12.5% by weight, in particular 2.5 to 10.0% by weight.

The sum of the active compounds, solvents and auxiliaries should be 100% by weight.

Thickeners include, for example, inorganic thickeners such as bentonite, colloidal silicic acid, aluminum monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone and their Copolymers, acrylates and methacrylates.

Colorants which may be mentioned are all colorants which are recognized for use in medicaments, which may be dissolved or suspended.

Adjuvants are also spreading oils such as cyclic and acyclic silicone oils such as di-2-ethylhexyl adipate, isopropyl myristate, dipropylene glycol pelargonate, dimethicone, and also ethylene oxide, propylene Its copolymers and trimers with oxides and formalin, fatty acid esters, triglycerides, fatty alcohols.

Antioxidants are for example sulfites or metasulfites, for example potassium metasulfite, ascorbic acid, butylated hydroxytoluene, butylated hydroxyanisole, tocopherol.

Light stabilizers are, for example, substances from the class of benzophenones or novantisol acids.

Adhesives are for example polymer thickening agents, for example cellulose derivatives, starch derivatives, polyacrylates, natural polymers such as alginates, gelatin.

Auxiliaries may also be emulsifiers, for example nonionic surfactants such as polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate, Alkylphenol polyglycol ethers; Amphoteric surfactants such as disodium N-lauryl-β-iminodinopropionate or lecithin; Anionic surfactants such as sodium lauryl sulfate, fatty alcohol ether sulfates, mono / dialkyl-polyglycol ether orthophosphoric acid ester monoethanolamine salts; Cationic surfactants such as cetyltrimethylammonium chloride.

Further auxiliaries are preparations in which the preparations according to the invention can be sprayed or squirted or rubbed together on the skin. These are conventional propellant gases required for spray cans, such as propane, butane, dimethylether, CO ₂ or halogenated lower alkanes, or mixtures of each other.

The preparations according to the invention, while low in toxicity to warm hematoma, are suitable for the control of parasitic insects encountered by humans. They are active against all or individual stages of pest development and against pests that are resistant or usually sensitive.

Pests

Anoplura, for example Pediculus spp., Pthirus spp .;

The order of the fleas (Siphonaptera), for example Ctenocephalides spp., Echidnophaga spp., Ceratophyllus spp.

Particularly mentioned are the actions on the eyes and fleas.

In this regard, Pediculus humanus (head tooth), Pediculus humanus corporis (body or garment tooth) and Phthivus pubis (hemorrhoids) Or action on pubic or crab louse.

The action on the ticks of the genus Astigmata, in particular Listrophoridae, Psoroptidae families and Sarcoptes, may be mentioned.

Use against Sabgeineus and further action on ticks such as Ixodes vicinus and Lipicepholus can be prophylactic and therapeutic.

The preparations according to the invention may further comprise juvenile hormones or larval hormonal substances, for example diaryl ether, benzoylurea or triazine. These materials include in particular compounds of the formula

Substituted diaryl ethers include compounds of the general formula:

R ¹ R ³ R ⁵ R ⁶ Z H H CH ₃ H O H H CH ₃ 2-Cl O 5-F H CH ₃ H O H H CF ₃ H O H H C ₂ H ₅ H O H H H H O H H CH ₃ H CH ₂ H H CH ₃ H C (CH ₃ ) ₂

Benzoylurea includes compounds of the general formula:

R ¹ R ² R ⁴ H Cl CF ₃ Cl Cl CF ₃ F F CF ₃ H F CF ₃ H Cl SCF ₃ F F SCF ₃ H F SCF ₃ H Cl OCF ₃ F F OCF ₃ H F OCF ₃ F F F F F F

Triazines include compounds of the general formula:

R ₁ R ₂ R ₃ Cyclopropyl H H Cyclopropyl H CH ₃ Cyclopropyl H C ₂ H ₅ Cyclopropyl H C ₃ H ₇ -n Cyclopropyl H C ₄ H ₉ -n Cyclopropyl H C ₅ H _11- n Cyclopropyl H C ₆ H ₁₃ -n Cyclopropyl H C ₇ H ₁₅ -n

(continue)

R ¹ R ² R ³ Cyclopropyl H C ₈ H ₁₇ -n Cyclopropyl H C ₁₂ -H ₂₅ -n Cyclopropyl H CH ₂ -C ₄ H ₉ -n Cyclopropyl H CH ₂ CH (CH ₃ ) C ₂ H ₅ Cyclopropyl H CH ₂ CH = CH ₂ Cyclopropyl Cl C ₂ H ₅ Cyclopropyl Cl C ₆ H ₁₃ -n Cyclopropyl Cl C ₈ H ₁₇ -n Cyclopropyl Cl C ₁₂ H ₂₅ -n Cyclopropyl H Cyclopropyl Cyclopropyl H COCH ₃ Cyclopropyl H COCH ₃ HCl Cyclopropyl H COC ₂ H ₅ HCl Cyclopropyl H COC ₂ H ₅ Cyclopropyl H COC ₃ H ₇ -n Cyclopropyl H COC ₃ H ₇ -i Cyclopropyl H COC ₄ H ₉ -t HCl Cyclopropyl H COC ₄ H ₉ -n Cyclopropyl H COC ₆ H ₁₃ -n

(continue)

R ₁ R ₂ R ₃ Cyclopropyl H COC ₁₁ -H ₂₃ -n Cyclopropyl COCH ₃ COC ₂ H ₅ Cyclopropyl COC ₃ H ₇ -n COC ₆ H ₁₃ -n Cyclopropyl COCH ₃ COC ₃ H ₇ -n Cyclopropyl COC ₂ H ₅ COC ₃ H ₇ -n Cyclopropyl H CO cyclopropyl Cyclopropyl CO cyclopropyl CO cyclopropyl Cyclopropyl COCH ₃ COCH ₃ Isopropyl H H Isopropyl H COCH ₃ Isopropyl H COC ₃ H ₇ -n Cyclopropyl H CONHCH ₃ Cyclopropyl H CONHC ₃ H ₇ -i Cyclopropyl CONHCH ₃ CONHCH ₃ Cyclopropyl H SCNHCH ₃ Cyclopropyl H CONHCH ₂ CH = CH ₂ Cyclopropyl CONHCH ₂ CH = CH ₂ CONHCH ₂ CH = CH ₂ Cyclopropyl CSNHCH ₃ CSNHCH ₃

The amount of additional active compound may be from 0 to 10% by weight, preferably up to 7.5%, particularly preferably up to 5.0%, based on the total formulation weight.

Active compounds that can be used for the purposes of the present invention are imidacloprid, AKD 1022 and Ti 435.

AKD 1022 is a chloronicotinyl derivative of the formula:

Ti 435 is a chloronicotinyl derivative of the formula:

In the examples below, the active compound employed is 1-[(6-chloro-3-pyridinyl) methyl] -N-nitro-2-imidazolidineimine (common name, imidacloprid).

Example 1

5 g of imidacloprids

75 g of propylene carbonate

19 g of isopropanol

^R Belsil DMC 6031 1 g

(Polysiloxane Copolymer from Wacker GmbH, D-81737 Munich, Germany)

Example 2

Imidacloprid 10 g

89 g of propylene carbonate

^R Belsil L 066 1 g

(Polysiloxane Copolymer from Wacker GmbH, D-81737 Munich, Germany)

Example 3

8.5 g of imidacloprids

Ethanol 30.0 g

60.5 g of ethylene carbonate

^R Bellsil L 066 1 g

(Polysiloxane Copolymer as Electrodeposition Agent)

Example 4

Imidacloprid 10 g

30.0 g of tetrahydrofurfuryl alcohol

59.9 g of propylene carbonate

^R Bellsil DMC 6031 0.1 g

(Polysiloxane Copolymer as Electrodeposition Agent)

Example 5

7.5 g of AKD 1022

70.0 g of isopropanol

22.5 g of propylene carbonate

Example 6

Ti 435 10.0 g

80.0 g of propylene carbonate

10.0 g of 2-octyl-1-dodecanol

Example 7

7.0 g of imidacloprid

89.0 g of propylene carbonate

4.0 g of isopropyl myristate

Example 8

12.5 g of imidacloprid

Benzyl Alcohol 70.0 g

17.4 g of propylene carbonate

0.1 g of butylated hydroxytoluene

Example 9

5.0 g of imidaclopride

22.5 g of ethanol

70 g of propylene carbonate

2.5 g of di-2-ethylhexyl adipate

Example 10

Imidacloprid 2.5 g

60.0 g of isopropanol

37.5 g of propylene carbonate

Example 11

Imidacloprid 2.5 g

1.0 g of pyriproxyfen

70.0 g of isopropanol

26.4 g of propylene carbonate

0.1 g of butylated hydroxytoluene

Example 12

Imidacloprid 2.5 g

12.5 g of isopropanol

60.0 g of propylene carbonate

25.0 g of propane / butane (15:85)

Spray formulations containing

Example 13

Imidacloprid 2.5 g

Ethanol 40.0 g

50.0 g of propylene carbonate

7.5 g of CO ₂

Spray formulations containing

Example 14

Imidacloprid 2.5 g

15.0 g of ethylene carbonate

15.0 g of propylene carbonate

Ethanol 20.0 g

47.5 g of diethyl ether

Spray formulations containing

Example of use

Two ml of the formulations described in Examples 1-11 were poured into the back of a dog weighing about 20 kg infected with head teeth. The following results were obtained:

The weight of these animals is comparable to the weight of children 6 to 8 years old.

Day Number of teeth per dog Action% Untreated process -1 infected with 100 teeth 0 processing and counting 35 0 100 5,8 infected with 100 teeth 9 factor 53 0 100 15 100 infected with teeth 16 modulus 79 0 100 19 Infected with 100 teeth (untreated animals) 250 Infected with teeth (treated animals) 20 modulus 45 0 100 26 Infected with 100 teeth 27 modulus 42 0 100

Toxicological experiments show that these agents do not cause any skin irritation in rats and rabbits.

The LD ₅₀ value of the formulation is> 1,800 mg / kg. The formulations have good spreading properties on animal fur. Therefore, the formulation will also have good results in humans.

Example B of use

2 ml of the solution according to Examples 12-14 were sprayed onto the shoulders of dogs weighing 20 kg. Animals were infected with 200 teeth after 2 days and treated 6 days later. Teeth remaining in dogs were counted on days 3 and 7 after treatment, respectively. No living teeth were found. The effect was 100%.

Toxicological experiments show that these agents do not cause any skin irritation in rats and rabbits. The formulations have good electrodeposition properties on animal fur and human skin.

Claims (4)

-An agonist or antagonist of nicotinic acetylcholine receptor at a concentration of 0.0001 to 20% by weight, based on the total weight of the formulation; A solvent selected from the group of cyclic carbonates at a concentration of 2.5 to 99.9999% by weight, based on the total weight of the formulation; If desired, further solvents selected from alcohol groups in concentrations of 0 to 95% by weight, based on the total weight of the formulation; -If desired, containing an additional adjuvant selected from the group of thickening agents, electrodeposition agents, colorants, antioxidants, propellants, preservatives, adhesives, emulsifiers at concentrations of 0 to 30% by weight, based on the total weight of the formulation. A composition for skin remedies of parasitic insects and ticks. A process for the preparation of a composition according to claim 1 characterized in that the active substance is mixed with the solvent (s) and further auxiliaries are added if desired. Use of the composition according to claim 1 for dermal relief of parasitic insects and ticks on humans. Use of a nicotine-effective acetylcholine receptor agonist or antagonist for the preparation of a composition for skin remedies of parasitic insects and ticks to humans.