EP1309320A2 - Anthelminthic agents for the prevention of parasitic infections in humans and animals ii - Google Patents
Anthelminthic agents for the prevention of parasitic infections in humans and animals iiInfo
- Publication number
- EP1309320A2 EP1309320A2 EP01945311A EP01945311A EP1309320A2 EP 1309320 A2 EP1309320 A2 EP 1309320A2 EP 01945311 A EP01945311 A EP 01945311A EP 01945311 A EP01945311 A EP 01945311A EP 1309320 A2 EP1309320 A2 EP 1309320A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- alkyl
- optionally substituted
- formula
- hydrogen
- different
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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- 208000030852 Parasitic disease Diseases 0.000 title description 2
- 230000002265 prevention Effects 0.000 title description 2
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 23
- 230000003071 parasitic effect Effects 0.000 claims abstract description 6
- 150000001875 compounds Chemical class 0.000 claims description 24
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- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 9
- 244000045947 parasite Species 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 9
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- 125000004429 atom Chemical group 0.000 claims description 7
- 244000000013 helminth Species 0.000 claims description 7
- 125000002950 monocyclic group Chemical group 0.000 claims description 7
- 230000007123 defense Effects 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
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- SASYSVUEVMOWPL-NXVVXOECSA-N decyl oleate Chemical compound CCCCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC SASYSVUEVMOWPL-NXVVXOECSA-N 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000036576 dermal application Effects 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
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- 230000007613 environmental effect Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 231100000722 genetic damage Toxicity 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 239000000383 hazardous chemical Substances 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000000077 insect repellent Substances 0.000 description 1
- 239000002563 ionic surfactant Substances 0.000 description 1
- 230000001678 irradiating effect Effects 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229940089456 isopropyl stearate Drugs 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- XJRBAMWJDBPFIM-UHFFFAOYSA-N methyl vinyl ether Chemical compound COC=C XJRBAMWJDBPFIM-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- REOJLIXKJWXUGB-UHFFFAOYSA-N mofebutazone Chemical group O=C1C(CCCC)C(=O)NN1C1=CC=CC=C1 REOJLIXKJWXUGB-UHFFFAOYSA-N 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- BARWIPMJPCRCTP-UHFFFAOYSA-N oleic acid oleyl ester Natural products CCCCCCCCC=CCCCCCCCCOC(=O)CCCCCCCC=CCCCCCCCC BARWIPMJPCRCTP-UHFFFAOYSA-N 0.000 description 1
- BARWIPMJPCRCTP-CLFAGFIQSA-N oleyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC BARWIPMJPCRCTP-CLFAGFIQSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- RWPGFSMJFRPDDP-UHFFFAOYSA-L potassium metabisulfite Chemical compound [K+].[K+].[O-]S(=O)S([O-])(=O)=O RWPGFSMJFRPDDP-UHFFFAOYSA-L 0.000 description 1
- 229940043349 potassium metabisulfite Drugs 0.000 description 1
- 235000010263 potassium metabisulphite Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- ZPWFUIUNWDIYCJ-UHFFFAOYSA-N propan-2-yl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(C)C ZPWFUIUNWDIYCJ-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- JNYAEWCLZODPBN-CTQIIAAMSA-N sorbitan Polymers OCC(O)C1OCC(O)[C@@H]1O JNYAEWCLZODPBN-CTQIIAAMSA-N 0.000 description 1
- 239000001587 sorbitan monostearate Substances 0.000 description 1
- 235000011076 sorbitan monostearate Nutrition 0.000 description 1
- 229940035048 sorbitan monostearate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000004544 spot-on Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 230000037072 sun protection Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 230000035900 sweating Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000003860 topical agent Substances 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- 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
-
- 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
- A61P33/12—Schistosomicides
Definitions
- Anthelmintics to prevent parasitic infections in humans and animals II
- the present invention relates to compositions containing certain active substances suitable as repellents and their use for preventing infection of humans or animals with the infection stages of parasitic flatworms (plathelminths).
- the agents are used on the skin against such stages of flatworms, so-called cercariae, which can penetrate through the skin into the host body.
- a pretreatment of the skin according to the invention with anthelmintic substances can, however, protect against the penetration of the pathogens.
- Hexachlorophene has a killing effect on cercariae from Schistosomas mansoni (Fripp, P.J. and Armstrong, F.L., The efficacy of hexachlorophene skin cleanser as a cercariae repellent. South African Med. J. 47: 1973, 526-527). Because of health risks, especially liver damage, hexachlorophene cannot be applied to the skin in humans. It is poisonous in contact with the skin and if swallowed, may cause malformations and may be carcinogenic [Commission of the European Communities, Directive 93/72 / EEC of 1 September. 1993, Appendix Vol. I and II (EU Hazardous Substances Ordinance) with additions up to 1999, Official Journal of EUL258A, 36th year, Oct. 16, 1993, additions up to 1997].
- Niclosamide acts against the penetration of cercariae [Bruce, J.I. et al. (1992) Efficacy of niclosamide as apotential topical antipenetrant (TAP) against cercariae of Schistosoma mansoni in monkeys. Mem. Inst. Oswaldo Cruz 87:28 1-289.] Is toxicologically unsafe because it can cause inheritable genetic damage (Registry of Toxic Effects of Chemical Substances, National Institute of Occupational Safety and Health). Application on the skin after exposure in
- N, N-Diethyl-m-toluamide acts on cercariae from Schistosoma mansoni [Salafsky, B. et al. Evaluation of N, N-diethyl-m-toluamide (DEET) as a topical agent for preventing skin penetration by cercariae of Schistosoma mansoni. At the. J. Trop. Med. Hyg. 58: 1998, 828-834).
- DEET has some unfavorable properties. The effects of the anthelmintics described so far against infectious stages of plathelminths have so far only been tested on cercariae of the species Schistosoma mansoni, so that the effectiveness of these agents against other types of worms has not been demonstrated.
- the agents according to the invention are suitable for providing effective protection for humans and animals against infections with plathelminths, in particular Schistosoma haematobium, Schistosoma japonicum, Trichobilharzia spp. and Omithobilharzia spp., but also Echinostoma spp. et al to offer.
- the invention accordingly relates to
- Y represents hydrogen, optionally substituted alkyl or the radical O-X,
- X represents hydrogen, COR 1 COOR 12 , R l3 ,
- R 1 represents optionally substituted alkyl or alkenyl radicals
- R 2 , R 11 , R 12 and R 13 are identical or different and represent optionally substituted alkyl or alkenyl radicals
- R 3 to R 10 are the same or different and represent hydrogen or optionally substituted alkenyl radicals, and where R 2 and R 3 together with the atoms to which they are attached can also form an optionally substituted monocyclic ring and
- n and m are the same or different and represent 0 or 1, with the proviso that X is not hydrogen or R 13 if n and m are 0.
- X represents hydrogen, COR 11 or R 13 ,
- R 1 represents Ci-C-alkyl or C 3 -C 7 -alkenyl
- R 2 , R n , R 13 are the same or different and are C 3 -C 6 alkyl
- R 3 to R 6 are the same or different and stand for hydrogen or Ci- - alkyl, where R 2 and R 3 together with the atoms to which they are attached can form a 5- or 6-membered monocyclic ring and n for 1 and
- R 2 and R 3 very particularly preferably form, together with the atoms to which they are attached, a 5- or 6-membered monocyclic ring, in particular a piperazine ring.
- the mosquitoes with their bites can transmit diseases such as malaria, various viruses, filaria and parasites, especially in the tropics.
- the agents according to the invention now enable simultaneous prevention against infections with platinum helminths and protection against mosquitoes with one agent. This avoids the need to use two different, possibly incompatible agents on the skin at the same time.
- the agents according to the invention can also contain all customary auxiliaries and additives which are used in formulations for topical application.
- the active ingredients are used directly or in the form of suitable preparations dermally or with the aid of shaped articles containing active ingredients, e.g. Strips, plates, ribbons, collars, ear tags, limb straps, marking devices.
- the dermal application happens e.g. in the form of bathing, diving (dipping), spraying (spraying), pouring on (pour-on or spot-on), washing, shampooing, watering, powdering.
- Suitable preparations are:
- Emulsions and suspensions for dermal use and semi-solid preparations are Emulsions and suspensions for dermal use and semi-solid preparations
- Formuherungen in which the active ingredient is processed in an ointment base or in an oil in water or water in oil emulsion base;
- Solid preparations such as powders, shaped articles containing active ingredients.
- Solutions for use on the skin are dripped on, spread on, rubbed in, sprayed on, sprayed on or applied by dipping (dipping), bathing or washing.
- the solutions are prepared by dissolving the active ingredient in a suitable solvent and possibly adding additives such as solubilizers, acids, bases, buffer salts, antioxidants, preservatives.
- solvents such as
- Alcohols such as ethanol, butanol, benzyl alcohol, glycerin, hydrocarbons, propylene glycol, polyethylene glycols, N-methyl-pyrrolidone, and mixtures thereof.
- the active ingredients can optionally also be dissolved in physiologically compatible vegetable or synthetic oils.
- solubilizers solvents which require the active ingredient to be dissolved in the main solvent or prevent it from precipitating.
- solvents which require the active ingredient to be dissolved in the main solvent or prevent it from precipitating.
- examples are polyvinyl pyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan esters.
- Preservatives are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester, n-butanol.
- Gels that are applied or spread on the skin are produced by adding enough thickening agent to solutions that have been prepared as described above to produce a clear mass with an ointment-like consistency.
- the thickeners specified above are used as thickeners. Pour-on formulations are poured or sprayed onto limited areas of the skin, the active ingredient being distributed over the surface of the body.
- pour-on formulations are prepared by dissolving, suspending or emulsifying the active ingredient in suitable skin-compatible solvents or solvent mixtures. If necessary, further auxiliaries such as dyes, antioxidants, light stabilizers and adhesives are added.
- solvents water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenylethanol, phenoxyethanol, esters such as ethyl acetate, butyl acetate, benzylbenzoate, ethers such as alkylene glycol alkyl ethers such as dipropylene glycol monomethyl ether, diethylene glycol, monobutyl glycol, monobutyl glycol Methyl ethyl ketone, aromatic and / or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, dimethylacetamide, N-methylpyrrolidone, 2-dimethyl-4-oxy-methylene-l, 3-dioxolane.
- aromatic alcohols such as benzyl alcohol, phenylethanol, phenoxyethanol
- esters such as ethyl acetate, butyl acetate
- benzylbenzoate
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention relates to agents containing particular active ingredients which can be used as repellents, and the use thereof to prevent humans or animals being infected by the stages of infection of parasitic flatworms (platyhelminths). Said active ingredients are cyclic or acyclic amides.
Description
Anthelmintika zur Verhinderung von parasitären Infektionen bei Mensch und Tier IIAnthelmintics to prevent parasitic infections in humans and animals II
Die vorliegende Erfindung betrifft Mittel enthaltend bestimmte, als Repellentien geeignete Wirkstoffe und deren Verwendung zur Verhinderung einer Infektion des Menschen bzw. von Tieren mit den Infektionsstadien von parasitischen Plattwürmern (Plathelminthen). Die Mittel kommen dabei auf der Haut gegen solche Stadien der Plattwürmer, sogenannte Cercarien, zum Einsatz, die durch die Haut in den Wirtskörper eindringen können.The present invention relates to compositions containing certain active substances suitable as repellents and their use for preventing infection of humans or animals with the infection stages of parasitic flatworms (plathelminths). The agents are used on the skin against such stages of flatworms, so-called cercariae, which can penetrate through the skin into the host body.
Mehrere Arten von Plathelminthen verursachen schwerwiegende Erkrankungen von Menschen und Tieren. In tropischen Ländern fuhren insbesondere Infektionen mit Schistosoma- Arten zu chronischem Leiden und oft zum Tod. Wichtige Erreger sind Schistosoma mansoni, Schistosoma haematobium und Schistosoma japomcum. Betroffen sind die einheimische Bevölkerung, Touristen, Mitarbeiter von humanitären Hilfsorganisationen sowie militärisches Personal. Bei der Infektion des Menschen können die infektionsfähigen Cercarien, die sich im Wasser offener Gewässer befinden, durch die Haut in den Körper eindringen.Several types of plathelminths cause serious human and animal diseases. In tropical countries, infections with Schistosoma species in particular lead to chronic suffering and often to death. Important pathogens are Schistosoma mansoni, Schistosoma haematobium and Schistosoma japomcum. The local population, tourists, humanitarian aid workers and military personnel are affected. When humans are infected, the infectious cercariae, which are found in open water, can penetrate the body through the skin.
Ebenfalls problematisch ist in Ländern mit gemäßigtem Klima der Befall vonThe infestation of is also problematic in countries with a temperate climate
Menschen mit Cercarien verschiedener Arten der Gattungen Trichobilharzia und Ornithobilharzia, die sich in die Haut einbohren und eine Dermatitis hervorrufen können. Solche Infekte erfolgen bei Freizeitaktivitäten an Binnengewässern oder Meeresküsten sowie bei Tätigkeiten in der Fischerei, Teichwirtschaft oder Feldbe- Wässerung. Generell ist in vielen Situationen des täglichen Lebens der Kontakt derPeople with cercariae of various types of the genera Trichobilharzia and Ornithobilharzia, who can dig into the skin and cause dermatitis. Such infections occur during leisure activities on inland waterways or sea coasts, as well as during activities in fishing, pond management or field irrigation. Generally, in many situations of everyday life, the contact is
Haut mit u. U. kontaminiertem/infiziertem Wasser unvermeidbar.Skin with u. U. contaminated / infected water inevitable.
Eine erfindungsgemäße Vorbehandlung der Haut mit anthelminthisch wirkenden Substanzen kann jedoch vor einem Eindringen der Erreger schützen.A pretreatment of the skin according to the invention with anthelmintic substances can, however, protect against the penetration of the pathogens.
In der Vergangenheit wurden bereits einige Verbindungen auf ihre Tauglichkeit zur Verhinderung von Infektionen mit solchen Parasiten getestet. Die bisher für die
erfindungsgemäßen Zwecke beschriebenen Substanzen sind jedoch toxisch, wenn sie durch die Haut oder nach oraler Aufnahme in den Körper gelangen:Some compounds have been tested in the past for their suitability for preventing infections with such parasites. So far for the However, substances described according to the purposes of the invention are toxic if they enter the body through the skin or after oral ingestion:
So zeigt z.B. Hexachlorophen eine abtötende Wirkung auf Cercarien von Schisto- soma mansoni (Fripp, P. J. and Armstrong, F. L, The efficacy of hexachlorophene skin cleanser as a cercariae repellent. South African Med. J. 47: 1973, 526-527). Hexachlorophen kann wegen gesundheitlicher Risiken, insbesondere Leberschäden, beim Menschen nicht auf der Haut angewandt werden. Es ist giftig bei Berührung mit der Haut und beim Verschlucken, kann möglicherweise Missbildungen hervor- rufen und ist eventuell krebserregend [Kommission der Europäischen Gemeinschaften, Richtlinie 93/72/EWG vom 1 .Sept. 1993, Anhang Bd. I und II (EU Gefahrstoff- Verordnung) mit Ergänzungen bis 1999, Amtsblatt der EUL258A, 36. Jahrgang, 16. Okt. 1993, Ergänzungen bis 1997].For example, Hexachlorophene has a killing effect on cercariae from Schistosomas mansoni (Fripp, P.J. and Armstrong, F.L., The efficacy of hexachlorophene skin cleanser as a cercariae repellent. South African Med. J. 47: 1973, 526-527). Because of health risks, especially liver damage, hexachlorophene cannot be applied to the skin in humans. It is poisonous in contact with the skin and if swallowed, may cause malformations and may be carcinogenic [Commission of the European Communities, Directive 93/72 / EEC of 1 September. 1993, Appendix Vol. I and II (EU Hazardous Substances Ordinance) with additions up to 1999, Official Journal of EUL258A, 36th year, Oct. 16, 1993, additions up to 1997].
Niclosamid wirkt gegen Eindringen von Cercarien [Bruce, J. I. et al. (1992) Efficacy of niclosamide as apotential topical antipenetrant (TAP) against cercariae of Schistosoma mansoni in monkeys. Mem. Inst. Oswaldo Cruz 87:28 1-289.] ist aber toxikologisch bedenklich, weil es möglicherweise vererbbare genetische Schäden verursachen kann (Registry of Toxic Effects of Chemical Substances, National Institute of Occupational Safety and Health). Die Anwendung auf der Haut bei Exposition inNiclosamide acts against the penetration of cercariae [Bruce, J.I. et al. (1992) Efficacy of niclosamide as apotential topical antipenetrant (TAP) against cercariae of Schistosoma mansoni in monkeys. Mem. Inst. Oswaldo Cruz 87:28 1-289.] Is toxicologically unsafe because it can cause inheritable genetic damage (Registry of Toxic Effects of Chemical Substances, National Institute of Occupational Safety and Health). Application on the skin after exposure in
Gewässern verbietet sich durch seine umweltgefährdende Eigenschaft, da Niclosamid stark wassergefährdend ist [Umweltbundesamt (Hrsg.)Katalog wassergefährdender Stoffe. LTwS-Nr. 12. Mai 1996 mit laufenden Ergänzungen, Berlin 1996]. Daher hat bisher keine kommerzielle Anwendung gegen Cercarien beim Menschen stattgefün- den.Water is forbidden due to its environmentally hazardous properties, since niclosamide is highly water-endangering [Federal Environment Agency (ed.) Catalog of water-endangering substances. LTwS no. May 12, 1996 with ongoing additions, Berlin 1996]. Therefore, no commercial use against cercariae has occurred in humans to date.
N, N-Diethyl-m-toluamid (DEET) wirkt auf Cercarien von Schistosoma mansoni [Salafsky, B. et al. Evaluation of N, N-diethyl-m-toluamide (DEET)as a topical agent for preventing skin penetration by cercariae of Schistosoma mansoni. Am. J. Trop. Med. Hyg. 58: 1998, 828- 834). DEET besitzt jedoch einige ungünstige Eigenschaften.
Die Wirkung der bisher beschriebenen Anthelminthika gegen infektiöse Stadien von Plathelminthen wurde bisher nur an Cercarien der Art Schistosoma mansoni getestet, so dass eine Wirksamkeit dieser Mittel gegen andere Wurmarten bislang nicht nachgewiesen war.N, N-Diethyl-m-toluamide (DEET) acts on cercariae from Schistosoma mansoni [Salafsky, B. et al. Evaluation of N, N-diethyl-m-toluamide (DEET) as a topical agent for preventing skin penetration by cercariae of Schistosoma mansoni. At the. J. Trop. Med. Hyg. 58: 1998, 828-834). However, DEET has some unfavorable properties. The effects of the anthelmintics described so far against infectious stages of plathelminths have so far only been tested on cercariae of the species Schistosoma mansoni, so that the effectiveness of these agents against other types of worms has not been demonstrated.
Es wurde nun überraschenderweise gefunden, dass die erfindungsgemäßen Mittel geeignet sind, um Mensch und Tier einen effektiven Schutz vor Infektionen mit Plathelminthen, insbesondere Schistosoma haematobium, Schistosoma japonicum, Trichobilharzia spp. und Omithobilharzia spp., aber auch Echinostoma spp. u.a. zu bieten.It has now surprisingly been found that the agents according to the invention are suitable for providing effective protection for humans and animals against infections with plathelminths, in particular Schistosoma haematobium, Schistosoma japonicum, Trichobilharzia spp. and Omithobilharzia spp., but also Echinostoma spp. et al to offer.
Die Erfindung betrifft demnachThe invention accordingly relates to
1. Mittel zur Abwehr von helminthischen Parasiten, gekennzeichnet durch einen Gehalt an mindestens einer Verbindung der Formel (I)1. Agent for defense against helminthic parasites, characterized by a content of at least one compound of the formula (I)
in welcher in which
Y für Wasserstoff, gegebenenfalls substituiertes Alkyl oder für den Rest O-X steht,Y represents hydrogen, optionally substituted alkyl or the radical O-X,
X für Wasserstoff, COR11, COOR12, Rl3 steht,X represents hydrogen, COR 11 , COOR12, Rl3,
R1 für einen gegebenenfalls substituierten Alkyl-, Alkenyl-, Cycloalkyl oder Cycloalkenylrest steht,
R2, R11, R12 und R13 gleich oder verschieden sind und für gegebenenfalls substituierte Alkyl- oder Alkenylreste stehen,R 1 represents an optionally substituted alkyl, alkenyl, cycloalkyl or cycloalkenyl radical, R 2 , R 11 , R 12 and R 13 are identical or different and represent optionally substituted alkyl or alkenyl radicals,
R3 bis R10 gleich oder verschieden sind und für Wasserstoff oder für gegebe- nenfalls substituierte Alkenylreste stehen und wobei R2 und R3 gemeinsam mit den Atomen, an welche sie gebunden sind auch einen gegebenenfalls substituierten monocyclischen Ring bilden können undR 3 to R 10 are the same or different and represent hydrogen or optionally substituted alkenyl radicals and where R 2 and R 3 together with the atoms to which they are bonded can also form an optionally substituted monocyclic ring and
n und m gleich oder verschieden sind und 0 oder 1 bedeuten, mit der Maß- gäbe, dass X nicht für Wasserstoff oder R13 steht, wenn n und m für 0 stehen.n and m are the same or different and denote 0 or 1, with the proviso that X is not hydrogen or R 13 if n and m are 0.
2. Mittel zur Abwehr von helminthischen Parasiten gemäß Punkt 1, gekennzeichnet durch einen Gehalt an mindestens einer Verbindung der Formel (I), in welcher2. Means for defense against helminthic parasites according to item 1, characterized by a content of at least one compound of the formula (I) in which
Y für Wasserstoff, Ci-Cö-Alkyl oder für den Rest O-X steht,Y represents hydrogen, Ci-C ö alkyl or the radical OX,
X für Wasserstoff, COR1 * oder R13 steht,X represents hydrogen, COR 1 * or R 13 ,
R1 für C3-C7-Cycloalkyl, C3-C7-Cycloalkenyl, C1-C2-Alkyl-C3-C7-Cyclo- alkyl, CrC2-Alkyl-C3-C -Cycloalkenyl, wobei die Cycloalkyl- oderR 1 for C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkenyl, C 1 -C 2 alkyl-C 3 -C 7 cycloalkyl, CrC 2 alkyl-C 3 -C cycloalkenyl, where the cycloalkyl or
Cycloalkenylringe der vorgenannten Reste gegebenenfalls bis zu dreifach durch C^-Cö-Alkyl oder durch eine Ci-Cg-Dialkylenbrücke substituiert sind oderCycloalkenyl rings of the aforementioned radicals are optionally substituted up to three times by C 1-6 alkyl or by a C 1 -C 6 -dialkylene bridge or
R1 für CrC7-Alkyl oder C3-C7-Alkenyl steht,R 1 represents C r C 7 alkyl or C 3 -C 7 alkenyl,
R2, R11, R13 gleich oder verschieden sind und für Ci-Cό- Alkyl stehen,
R3 bis R6 gleich oder verschieden sind und für Wasserstoff oder C^-Cg- Alkyl stehen, wobei R2 und R3 gemeinsam mit den Atomen, an welche sie gebunden sind, einen 5- oder 6-gliedrigen monocyclischen Ring bilden können undR 2 , R 11 , R 13 are the same or different and represent Ci-Cό- alkyl, R 3 to R 6 are the same or different and represent hydrogen or C 1 -C 6 -alkyl, where R 2 and R 3 together with the atoms to which they are attached can form a 5- or 6-membered monocyclic ring and
n für 1 undn for 1 and
m für 0 steht.m stands for 0.
3. Verfahren zur Bekämpfung von parasitischen Helminthen, dadurch gekennzeichnet, dass man Verbindungen der Formel (I) gemäß Punkt 1 auf Helminthen und/oder ihren Lebensraum einwirken lässt.3. A method for combating parasitic helminths, characterized in that compounds of the formula (I) according to item 1 are allowed to act on helminths and / or their habitat.
4. Verwendung von Verbindungen der Formel (I) gemäß Punkt 1 zur Be- kämpfung von parasitischen Helminthen.4. Use of compounds of the formula (I) according to item 1 for controlling parasitic helminths.
5. Verfahren zur Herstellung von Mitteln zur Abwehr von helminthischen Parasiten, dadurch gekennzeichnet, dass man Verbindungen der Formel (I) gemäß Punkt 1 mit Streckmitteln und/oder oberflächenaktiven Mitteln vermischt.5. A process for the preparation of agents for defense against helminthic parasites, characterized in that compounds of the formula (I) according to item 1 are mixed with extenders and / or surface-active agents.
Gemäß einer bevorzugten Ausführungsform steht in Formel (I) der Substituent Y für Wasserstoff oder -Ce- Alkyl, wie z. B. Methyl, Ethyl, Propyl, Isopropyl, n-Butyl, sek.-Butyl, iso-Butyl oder tert.-Butyl, Pentyl oder Hexyl. In diesem Fall steht R1 bevorzugt für C3-C7-Cycloalkyl, C3-C7-Cycloalkenyl, C1-C2-Alkyl-C3-C7-Cyclo- alkyl, C1-C2-Alkyl-C3-C7-Cycloalkenyl, wobei die Cycloalkyl- oder Cycloalkenyl- ringe der vorgenannten Reste gegebenenfalls bis zu dreifach durch C^Cg- Alkyl oder durch eine Cj-Cg-Dialkylenbrücke substituiert sind.According to a preferred embodiment in formula (I) the substituent Y is hydrogen or -Ce-alkyl, such as. B. methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, iso-butyl or tert-butyl, pentyl or hexyl. In this case, R 1 preferably represents C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkenyl, C 1 -C 2 alkyl-C 3 -C 7 cycloalkyl, C 1 -C 2 alkyl- C 3 -C 7 cycloalkenyl, the cycloalkyl or cycloalkenyl rings of the abovementioned radicals optionally being substituted up to three times by C 1 -C 6 -alkyl or by a C 1 -C 6 -dialkylene bridge.
Gemäß einer weiteren Ausführungsform geeignet für den Einsatz in den erfmdungs- gemäßen Mitteln sind Verbindungen der Formel (I), in welcher
Y für den Rest O-X steht,According to a further embodiment, compounds of the formula (I) in which are suitable for use in the agents according to the invention Y stands for the rest OX,
X für Wasserstoff, COR1 COOR12, Rl3 steht,X represents hydrogen, COR 1 COOR 12 , R l3 ,
R1 für gegebenenfalls substituierte Alkyl- oder Alkenylreste steht,R 1 represents optionally substituted alkyl or alkenyl radicals,
R2, R11, R12 und R13 gleich oder verschieden sind und für gegebenenfalls substituierte Alkyl- oder Alkenylreste stehen,R 2 , R 11 , R 12 and R 13 are identical or different and represent optionally substituted alkyl or alkenyl radicals,
R3 bis R10 gleich oder verschieden sind und für Wasserstoff oder für gegebenenfalls substituierte Alkenylreste stehen und wobei R2 und R3 gemeinsam mit den Atomen, an welche sie gebunden sind auch einen gegebenenfalls substituierten monocyclischen Ring bilden können undR 3 to R 10 are the same or different and represent hydrogen or optionally substituted alkenyl radicals, and where R 2 and R 3 together with the atoms to which they are attached can also form an optionally substituted monocyclic ring and
n und m gleich oder verschieden sind und 0 oder 1 bedeuten, mit der Maßgabe, dass X nicht für Wasserstoff oder R13 steht, wenn n und m für 0 stehen.n and m are the same or different and represent 0 or 1, with the proviso that X is not hydrogen or R 13 if n and m are 0.
sen besonders geeignet sind Verbindungen der Formel (I), in welcherCompounds of the formula (I) in which
X für Wasserstoff, COR11 oder R13 steht,X represents hydrogen, COR 11 or R 13 ,
R1 für Ci-C -Alkyl oder C3-C7-Alkenyl steht,R 1 represents Ci-C-alkyl or C 3 -C 7 -alkenyl,
R2, Rn, R13 gleich oder verschieden sind und für C3-C6- Alkyl stehen,R 2 , R n , R 13 are the same or different and are C 3 -C 6 alkyl,
R3 bis R6 gleich oder verschieden sind und fürWasserstoff oder Ci- - Alkyl stehen, wobei R2 und R3 gemeinsam mit den Atomen, an welche sie gebunden sind, einen 5- oder 6-gliedrigen monocyclischen Ring bil- den können und
n für 1 undR 3 to R 6 are the same or different and stand for hydrogen or Ci- - alkyl, where R 2 and R 3 together with the atoms to which they are attached can form a 5- or 6-membered monocyclic ring and n for 1 and
m für 0 steht.m stands for 0.
In diesen Verbindungen bilden R2 und R3 ganz besonders bevorzugt gemeinsam mit den Atomen, an welche sie gebunden sind, einen 5- oder 6-gliedrigen monocyclischen Ring, insbesondere einen Piperazinring.In these compounds, R 2 and R 3 very particularly preferably form, together with the atoms to which they are attached, a 5- or 6-membered monocyclic ring, in particular a piperazine ring.
Von diesen wiederum besonders geeignet sind die Verbindungen der Formel (la)Of these, the compounds of the formula (Ia) are particularly suitable.
woπn embedded image in which
X für Wasserstoff, COR11, COOR12, R13 steht, wobei R1 \ R12 und R13 gleich oder verschieden sind und für gegebenenfalls substituierte Alkyl- oder Alkenylreste , insbesondere für Wasserstoff oder CrGrAlkyl, wie z. B.X represents hydrogen, COR 11 , COOR 12 , R 13 , where R 1 \ R 12 and R 13 are the same or different and for optionally substituted alkyl or alkenyl radicals, in particular for hydrogen or CrGrAlkyl, such as. B.
Methyl, Ethyl, Propyl, Isopropyl, n-Butyl, sek.-Butyl, iso-Butyl oder teri-Methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, iso-butyl or teri-
Butyl, stehen undButyl, stand and
R1 für CrC6-Alkyl oder für C3-C6-Alkenyl steht.R 1 represents C r C 6 alkyl or C 3 -C 6 alkenyl.
Im einzelnen seien die folgenden Verbindungen der Formel (I) bzw. (Ia)In particular, the following compounds of the formula (I) or (Ia)
als besonders geeignet für die Verwendung in den erfindungsgemäßen Mitteln genannt. mentioned as particularly suitable for use in the agents according to the invention.
Die Verbindungen der Formel (I) und (la) und ihre Herstellung sind aus DE OS 37 08 033 bekannt.The compounds of formula (I) and (la) and their preparation are known from DE OS 37 08 033.
Ebenfalls zur erfindungsgemäßen Verwendung geeignet ist die folgende Verbindung der Formel (I)The following compound of the formula (I) is also suitable for use according to the invention
Diese Verbindung ist bekannt und kommerziell erhältlich.This compound is known and commercially available.
Die in den erfindungsgemäßen Mitteln enthaltenen Wirkstoffe wurden bereits speziell zur Verwendung als Repellent auf der Haut gegen Insekten und Zecken eingesetzt.The active substances contained in the agents according to the invention have already been used specifically for use as repellants on the skin against insects and ticks.
Ein wesentlicher Vorteil der Verwendung der erfindungsgemäßen Verbindungen ist deren hohe Haut-, Pflanzen- und Umweltverträglichkeit und die generell geringe Toxizität dieser Verbindungen .A major advantage of using the compounds according to the invention is their high skin, plant and environmental compatibility and the generally low toxicity of these compounds.
Es ist weiterhin wünschenswert, beim Aufenthalt im Freien gegen Moskitos geschützt zu sein, die zum einen als belästigend empfunden werden, zum anderen können die Moskitos mit ihren Stichen speziell in den Tropen Krankheiten wie Malaria, verschiedene Viren, Filarien und Parasiten übertragen. Die erfindungsgemäßen Mittel ermöglichen nun die gleichzeitige Prävention vor Infektionen mit Plathelminthen und Schutz vor Moskitos mit einem Mittel. Damit wird die Notwendigkeit der gleichzeitigen Anwendung von zwei verschiedenen, möglicherweise nicht miteinander verträglichen Mitteln auf der Haut vermieden.
Die erfindungsgemäßen Mittel können neben den Wirkstoffen auch alle üblichen Hilfs- und Zusatzstoffe enthalten, welche in Formulierungen zur topikalen Applikation verwendet werden.It is also desirable to be protected against mosquitoes when they are outdoors, which on the one hand is perceived as annoying and on the other hand, the mosquitoes with their bites can transmit diseases such as malaria, various viruses, filaria and parasites, especially in the tropics. The agents according to the invention now enable simultaneous prevention against infections with platinum helminths and protection against mosquitoes with one agent. This avoids the need to use two different, possibly incompatible agents on the skin at the same time. In addition to the active ingredients, the agents according to the invention can also contain all customary auxiliaries and additives which are used in formulations for topical application.
Die Anwendung der Wirkstoffe erfolgt direkt oder in Form von geeigneten Zubereitungen dermal oder mit Hilfe wirkstoffhaltiger Formkörper wie z.B. Streifen, Platten, Bänder, Halsbänder, Ohrmarken, Gliedmaßeribänder, Markierungsvorrichtungen.The active ingredients are used directly or in the form of suitable preparations dermally or with the aid of shaped articles containing active ingredients, e.g. Strips, plates, ribbons, collars, ear tags, limb straps, marking devices.
Die dermale Anwendung geschieht z.B. in Form des Badens, Tauchens (Dippen), Sprühens (Sprayen), Aufgießens (pour-on oder spot-on), Waschens, Schamponierens, Begießens, Einpuderns.The dermal application happens e.g. in the form of bathing, diving (dipping), spraying (spraying), pouring on (pour-on or spot-on), washing, shampooing, watering, powdering.
Geeignete Zubereitungen sind:Suitable preparations are:
Lösungen oder Konzentrate zur Verabreichung nach Verdünnung, Lösungen zum Gebrauch auf der Haut, Aufgußformulierungen, Gele;Solutions or concentrates for administration after dilution, solutions for use on the skin, infusion formulations, gels;
Emulsionen und Suspensionen zur dermalen Anwendung sowie halbfeste Zuberei- tungen;Emulsions and suspensions for dermal use and semi-solid preparations;
Formuherungen, bei denen der Wirkstoff in einer Salbengrundlage oder in einer Öl in Wasser oder Wasser in Öl Emulsionsgrundlage verarbeitet ist;Formuherungen in which the active ingredient is processed in an ointment base or in an oil in water or water in oil emulsion base;
Feste Zubereitungen wie Pulver, wirkstoffhaltige Formkörper.Solid preparations such as powders, shaped articles containing active ingredients.
Lösungen zum Gebrauch auf der Haut werden aufgeträufelt, aufgestrichen, eingerieben, aufgespritzt, aufgesprüht oder durch Tauchen (Dippen), Baden oder Waschen aufgebracht.
Die Lösungen werden hergestellt, indem der Wirkstoff in einem geeigneten Lösungsmittel gelöst wird und evtl. Zusätze wie Lösungsvermittler, Säuren, Basen, Puffersalze, Antioxidantien, Konservierungsmittel zugefügt werden.Solutions for use on the skin are dripped on, spread on, rubbed in, sprayed on, sprayed on or applied by dipping (dipping), bathing or washing. The solutions are prepared by dissolving the active ingredient in a suitable solvent and possibly adding additives such as solubilizers, acids, bases, buffer salts, antioxidants, preservatives.
Als Lösungsmittel seien genannt: Physiologisch verträgliche Lösungsmittel wieThe following may be mentioned as solvents: Physiologically compatible solvents such as
Wasser, Alkohole wie Ethanol, Butanol, Benzylakohol, Glycerin, Kohlenwasserstoffe, Propylenglykol, Polyethylenglykole, N-Methyl-pyrrolidon, sowie Gemische derselben.Water, alcohols such as ethanol, butanol, benzyl alcohol, glycerin, hydrocarbons, propylene glycol, polyethylene glycols, N-methyl-pyrrolidone, and mixtures thereof.
Die Wirkstoffe lassen sich gegebenenfalls auch in physiologisch verträglichen pflanzlichen oder synthetischen Ölen lösen.The active ingredients can optionally also be dissolved in physiologically compatible vegetable or synthetic oils.
Als Lösungsvermittler seien genannt: Lösungsmittel, die die Lösung des Wirkstoffs im Hauptlösungsmittel fordern oder sein Ausfallen verhindern. Beispiele sind Polyvi- nylpyrrolidon, polyoxyethyliertes Rhizinusöl, polyoxyethylierte Sorbitanester.The following may be mentioned as solubilizers: solvents which require the active ingredient to be dissolved in the main solvent or prevent it from precipitating. Examples are polyvinyl pyrrolidone, polyoxyethylated castor oil, polyoxyethylated sorbitan esters.
Konservierungsmittel sind: Benzylalkohol, Trichlorbutanol, p-Hydroxybenzoesäure- ester, n-Butanol.Preservatives are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoic acid ester, n-butanol.
Es kann vorteilhaft sein, bei der Herstellung der Lösungen Verdickungsmittel zuzufügen. Verdickungsmittel sind: Anorganische Verdickungsmittel wie Bentonite, kolloidale Kieselsäure, Aluminiummonostearat, organische Verdickungsmittel wie Cellulosederivate, Polyvinylalkohole und deren Copolymere, Acrylate und Meth- acrylate.It may be advantageous to add thickeners when preparing the solutions. Thickeners are: inorganic thickeners such as bentonites, colloidal silica, aluminum monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohols and their copolymers, acrylates and methacrylates.
Gele, die auf die Haut aufgetragen oder aufgestrichen werden, werden hergestellt indem Lösungen, die wie oben beschrieben hergestellt worden sind, mit soviel Verdickungsmittel versetzt werden, dass eine klare Masse mit salbenartiger Konsistenz entsteht. Als Verdickungsmittel werden die weiter oben angegebenen Verdickungsmittel eingesetzt.
Aufgießformulierungen werden auf begrenzte Bereiche der Haut aufgegossen oder aufgespritzt, wobei der Wirkstoffsich auf der Körperoberfläche verteilt.Gels that are applied or spread on the skin are produced by adding enough thickening agent to solutions that have been prepared as described above to produce a clear mass with an ointment-like consistency. The thickeners specified above are used as thickeners. Pour-on formulations are poured or sprayed onto limited areas of the skin, the active ingredient being distributed over the surface of the body.
Aufgießformulierungen werden hergestellt, indem der Wirkstoff in geeigneten hautverträglichen Lösungsmitteln oder Lösungsmittelgemischen gelöst, suspendiert oder emulgiert wird. Gegebenenfalls werden weitere Hilfsstoffe wie Farbstoffe, Antioxidantien, Lichtschutzmittel, Haftmittel zugefügt.Pour-on formulations are prepared by dissolving, suspending or emulsifying the active ingredient in suitable skin-compatible solvents or solvent mixtures. If necessary, further auxiliaries such as dyes, antioxidants, light stabilizers and adhesives are added.
Als Lösungsmittel seien genannt: Wasser, Alkanole, Glycole, Polyethylenglycole, Polypropylenglycole, Glycerin, aromatische Alkohole wie Benzylalkohol, Phenyl- ethanol, Phenoxyethanol, Ester wie Essigester, Butylacetat, Benzylbenzoat, Ether wie Alkylenglykolalkylether wie Dipropylenglykolmonomethylether, Diethylenglykol- monobutylether, Ketone wie Aceton, Methylethylketon, aromatische und/oder aliphatische Kohlenwasserstoffe, pflanzliche oder synthetische Öle, DMF, Dimethylacetamid, N-Methylpyrrolidon, 2-Dimethyl-4-oxy-methylen-l ,3-dioxolan.The following may be mentioned as solvents: water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenylethanol, phenoxyethanol, esters such as ethyl acetate, butyl acetate, benzylbenzoate, ethers such as alkylene glycol alkyl ethers such as dipropylene glycol monomethyl ether, diethylene glycol, monobutyl glycol, monobutyl glycol Methyl ethyl ketone, aromatic and / or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, dimethylacetamide, N-methylpyrrolidone, 2-dimethyl-4-oxy-methylene-l, 3-dioxolane.
Farbstoffe sind alle zur Anwendung am Tier zugelassenen Farbstoffe, die gelöst oder suspendiert sein können.Dyes are all dyes approved for use on animals, which can be dissolved or suspended.
Hilfsstoffe sind auch spreitende Öle wie Isopropylmyristat, Dipropylenglykol- pelargonat, Silikonöle, Fettsäureester, Triglyceride, Fettalkohole.Excipients are also spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides, fatty alcohols.
Antioxidantien sind Sulfite oder Metabisulfite wie Kahummetabisulfit, Ascorbinsäure, Butylhydroxytoluol, Butylhydroxyanisol, Tocopherol.Antioxidants are sulfites or metabisulfites such as potassium metabisulfite, ascorbic acid, butylated hydroxytoluene, butylated hydroxyanisole, tocopherol.
Lichtschutzmittel sind z.B. Stoffe aus der Klasse der Benzophenone oder Novantisol- säure.Light stabilizers are e.g. Substances from the class of benzophenones or novantisolic acid.
Haftmittel sind z.B. Cellulosederivate, Stärkederivate, Polyacrylate, natürliche Polymere wie Alginate, Gelatine.
Emulsionen sind entweder vom Typ Wasser in Öl oder vom Typ Öl in Wasser.Adhesives are, for example, cellulose derivatives, starch derivatives, polyacrylates, natural polymers such as alginates, gelatin. Emulsions are either water in oil or oil in water.
Sie werden hergestellt, indem man den Wirkstoff entweder in der hydrophoben oder in der hydrophilen Phase löst und diese unter Zuhilfenahme geeigneter Emulgatoren und gegebenenfalls weiterer Hilfsstoffe wie Farbstoffe, resorptionsfordemde Stoffe,They are produced by dissolving the active ingredient either in the hydrophobic or in the hydrophilic phase and, with the aid of suitable emulsifiers and, if appropriate, other auxiliaries such as dyes, absorption-promoting substances,
Konservierungsstoffe, Antioxidantien, Lichtschutzmittel, viskositätserhöhende Stoffe, mit dem Lösungsmittel der anderen Phase homogenisiert.Preservatives, antioxidants, light stabilizers, viscosity-increasing substances, homogenized with the solvent of the other phase.
Als hydrophobe Phase (Öle) seien genannt: Paraffinöle, Silikonöle, natürliche Pflanzenöle wie Sesamöl, Mandelöl, Rizinusöl, synthetische Triglyceride wie Capryl/The following may be mentioned as the hydrophobic phase (oils): paraffin oils, silicone oils, natural vegetable oils such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic /
Caprinsäurebiglycerid, Triglyceridgemisch mit Pflanzenfettsäuren der Kettenlänge C8-12 oder anderen speziell ausgewählten natürlichen Fettsäuren, Partialglycerid- gemische gesättigter oder ungesättigter eventuell auch hydroxylgruppenhaltiger Fettsäuren, Mono- und Diglyceride der Cs/Cto-Fettsäuren.Caprinsäurebiglycerid, triglyceride mixture with vegetable fatty acids of chain length C8-12 or other natural fatty acids, Partialglycerid- specially selected mixtures of saturated or unsaturated fatty acids possibly also containing hydroxyl groups, mono- and diglycerides of the Cs / C o t-fatty acids.
Fettsäureester wie Ethylstearat, Di-n-butyryl-adipat, Laurinsäurehexylester, Dipropy- len-glykolpelargonat, Ester einer verzweigten Fettsäure mittlerer Kettenlänge mit gesättigten Fettalkoholen der Kettenlänge C 6-C18, Isopropylmyristat, Isopropyl- palmitat, Capryl/Caprinsäureester von gesättigten Fettalkoholen der Kettenlänge C12-C18, Isopropylstearat, Ölsäureoleylester, Ölsäuredecylester, Ethyloleat, Milch- säureethylester, wachsartige Fettsäureester wie Dibutylphthalat, Adipinsäurediiso- propylester, letzterem verwandte Estergemische u.a. Fettalkohole wie Isotride- cylalkohol, 2-Octyldodecanol, Cetylstearyl-alkohol, Oleylalkohol.Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, lauric acid hexyl ester, dipropylene glycol pelargonate, esters of a branched fatty acid of medium chain length with saturated fatty alcohols of chain length C 6 -C 18 , isopropyl myristate, isopropyl palmitate, caprylic / capric alcohol esters of saturated fatty alcohol Chain length C 12 -C 18 , isopropyl stearate, oleic acid oleyl ester, oleic acid decyl ester, ethyl oleate, lactic acid ethyl ester, waxy fatty acid esters such as dibutyl phthalate, adipic acid diisopropyl ester, the latter related ester mixtures including fatty alcohols such as isotride-cyl alcohol, 2-octyl alcohol, 2-octyl alcohol, 2-octyl alcohol doleyl alcohol.
Fettsäuren wie z.B. Ölsäure und ihre Gemische.Fatty acids such as Oleic acid and its mixtures.
Als hydrophile Phase seien genannt:The following can be mentioned as the hydrophilic phase:
Wasser, Alkohole wie z.B. Propylenglycol, Glycerin, Sorbitol und ihre Gemische.
Als Emulgatoren seien genannt: nichtionogene Tenside, z.B. polyoxyethyliertes Rizinusöl, polyoxyethyhertes Sorbitanmonooleat, Sorbitanmonostearat, Glycerinmono- stearat, Polyoxyethylstearat, Alkylphenolpolyglykolether;Water, alcohols such as propylene glycol, glycerin, sorbitol and their mixtures. The following may be mentioned as emulsifiers: nonionic surfactants, for example polyoxyethylated castor oil, polyoxyethylene sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate, alkylphenol polyglycol ether;
ampholytische Tenside wie Di-Na-N-lauryl-ß-iminodipropionat oder Lecithin;ampholytic surfactants such as di-Na-N-lauryl-β-iminodipropionate or lecithin;
anionaktive Tenside, wie Na-Laurylsulfat, Fettalkoholethersulfate, Mono/Dialkylpoly- glykoletherorthophosphorsäureestermonoethanolaminsalz; kationaktive Tenside wie Cetyltrimethylammoniumchlorid.anionic surfactants, such as sodium lauryl sulfate, fatty alcohol ether sulfates, mono / dialkyl polyglycol ether orthophosphoric acid ester monoethanolamine salt; cationic surfactants such as cetyltrimethylammonium chloride.
Als weitere Hilfsstoffe seien genannt: Viskositätserhöhende und die Emulsion stabilisierende Stoffe wie Carboxymethylcellulose, Methylcellulose und andere Cellulose- und Stärke-Derivate, Polyacrylate, Alginate, Gelatine, Gummi-arabicum, Polyvinylpyrrolidon, Polyvinylalkohol, Copolymere aus Methylvinylether und Malein- Säureanhydrid, Polyethylenglykole, Wachse, kolloidale Kieselsäure oder Gemische der aufgeführten Stoffe.The following may be mentioned as further auxiliaries: substances which increase viscosity and stabilize the emulsion, such as carboxymethyl cellulose, methyl cellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinyl pyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycols, waxes , colloidal silica or mixtures of the listed substances.
Suspensionen werden hergestellt, indem man den Wirkstoff in einer Trägerflüssigkeit gegebenenfalls unter Zusatz weiterer Hilfsstoffe wie Netzmittel, Farbstoffe, resorp- tionsfördernde Stoffe, Konservierungsstoffe, Antioxidantien, Lichtschutzmittel suspendiert.Suspensions are produced by suspending the active ingredient in a carrier liquid, optionally with the addition of other auxiliary substances such as wetting agents, dyes, absorption-promoting substances, preservatives, antioxidants, light stabilizers.
Als Trägerflüssigkeiten seien alle homogenen Lösungsmittel und Lösungsmittelgemische genannt.All homogeneous solvents and solvent mixtures may be mentioned as carrier liquids.
Als Netzmittel (Dispergiermittel) seien die weiter oben angegebenen Tenside genannt.The surfactants specified above may be mentioned as wetting agents (dispersants).
Als weitere Hilfsstoffe seien die weiter oben angegebenen genannt.Further additives mentioned are those mentioned above.
Halbfeste Zubereitungen zur dermalen Verabreichung unterscheiden sich von den oben beschriebenen Suspensionen und Emulsionen nur durch ihre höhere Viskosität.
Zur Herstellung fester Zubereitungen wird der Wirkstoff mit geeigneten Trägerstoffen gegebenenfalls unter Zusatz von Hilfsstoffen vermischt und in die gewünschte Form gebracht.Semi-solid preparations for dermal administration differ from the suspensions and emulsions described above only in their higher viscosity. To prepare solid preparations, the active ingredient is mixed with suitable carriers, if appropriate with the addition of auxiliaries, and brought into the desired shape.
Als Trägerstoffe seien genannt alle physiologisch verträglichen festen Inertstoffe. Als solche dienen anorganische und organische Stoffe. Anorganische Stoffe sind z.B. Kochsalz, Carbonate wie Calciumcarbonat, Hydrogencarbonate, Aluminiumoxide, Kieselsäuren, Tonerden, gefälltes oder kolloidales Siliciumdioxid, Phosphate.All physiologically compatible solid inert substances may be mentioned as carriers. Inorganic and organic substances serve as such. Inorganic substances are e.g. Table salt, carbonates such as calcium carbonate, hydrogen carbonates, aluminum oxides, silicas, clays, precipitated or colloidal silicon dioxide, phosphates.
Hilfsstoffe sind Konservierungsstoffe, Antioxidantien, Farbstoffe, die bereits weiter oben aufgeführt worden sind.Excipients are preservatives, antioxidants, dyes, which have already been listed above.
Weitere geeignete Hilfsstoffe sind Schmier- und Gleitmittel wie z.B. Magnesiumstea- rat, Stearinsäure, Talkum, Bentonite.Other suitable auxiliaries are lubricants and lubricants such as Magnesium stearate, stearic acid, talc, bentonite.
Weiterhin ist es wünschenswert, dass ein solches Schutzmittel auch noch nach längerem Wasserkontakt, beispielsweise beim Schwimmen, Kleiderwaschen oder Fischen, noch eine ausreichende Schutzwirkung zeigt. Zu diesem Zweck können die erfin- dungsgemäßen Mittel auch wasserabweisende bzw. wasserfeste Substanzen enthalten.Furthermore, it is desirable that such a protective agent still has a sufficient protective effect even after prolonged contact with water, for example when swimming, washing clothes or fishing. For this purpose, the agents according to the invention can also contain water-repellent or water-resistant substances.
Geeignete wasserfeste Substanzen wurden bisher schon in Sonnenschutzmitteln eingesetzt, die den Benutzer gegen die UV-Strahlung der Sonne schützen sollen (z. B. US 55 18712 und US 4810489). Das Ziel war dabei, den Sonnenschutz auch aufrecht zu erhalten wenn der Benutzer schwimmen war oder heftig schwitzt etc. Sonnenschutzmittel enthaltend solche wasserfesten bzw. wasserabweisenden Substanzen und Insektenrepellentien sind bereits bekannt (US5716602). Bisher wurden jedoch noch keine Mittel, enthaltend Anthelminthika beschrieben.Suitable waterproof substances have previously been used in sunscreens which are intended to protect the user against the UV radiation from the sun (for example US 55 18712 and US 4810489). The aim was to maintain sun protection even when the user was swimming or sweating profusely, etc. Sunscreen compositions containing such water-resistant or water-repellent substances and insect repellents are already known (US5716602). However, no agents containing anthelmintics have yet been described.
Es können dementsprechend auch wasserfeste Substanzen im erfindungsgemäßen
Mittel enthalten sein. Dies können fettlösliche, wasserunlösliche Stoffe sein sowie Verbindungen welche die Haftung des Mittels auf der Haut erhöhen.Accordingly, waterproof substances can also be used in the invention Means be included. These can be fat-soluble, water-insoluble substances as well as compounds that increase the adhesion of the agent to the skin.
In Hautschutzprodukten könnten als wasserfeste Bestandteile beispielsweise 1- 50 Gew. % eines Polymers wie Polyinylpyrrolidone, Polyacrylate, Silicone etc. enthalten sein.Skin protection products could contain, for example, 1-50% by weight of a polymer, such as polyynylpyrrolidones, polyacrylates, silicones, etc., as water-resistant components.
Die Mittel zur topischen Anwendung können als Spray, Lösung, Creme, Salbe oder schicht- bzw. filmbildende Mittel, nach den zur Herstellung von Kosmetika bekann- ten Verfahren (Schrader, K. (1979) Grundlagen und Rezepturen der Kosmetika. Dr.The agents for topical use can be used as a spray, solution, cream, ointment or layer- or film-forming agent, according to the methods known for the production of cosmetics (Schrader, K. (1979) fundamentals and formulations of cosmetics.
Alfred Hüthig Verlag, Heidelberg), formuliert werden.Alfred Hüthig Verlag, Heidelberg).
Zur Anwendung werden die erfindungsgemäßen Formulierungen in verbrauchergerechter Menge gleichmäßig und lückenlos abdeckend auf die Haut aufgetragen.For use, the formulations according to the invention are applied to the skin uniformly and without gaps in a consumer-appropriate amount.
Die erfindungsgemäßen Mittel sind selbstverständlich auch zur Anwendung am Tier geeignet, um die Infektion der Tiere mit Parasiten dieser Gattungen zu verhindern. Die Mittel können bei Hobbytieren, wie beispielsweise Hunden und Katzen und bei Nutztieren, beispielsweise Rindern, Schweinen, Schafen u. a. angewendet werden.The agents according to the invention are of course also suitable for use on animals in order to prevent infection of the animals with parasites of these genera. The agents can be used in pet animals such as dogs and cats and in farm animals such as cattle, pigs, sheep and the like. a. be applied.
Bei der Anwendung der erfindungsgemäßen Mittel werden im allgemeinen 0,03 bis 1 mg, bevorzugt 0,03 bis 0,1 mg und besonders bevorzugt 0,04 bis 0,06 mg des Wirkstoffes pro Quadratzentimeter Haut aufgebracht. Dadurch wird em prophylaktischer Schutz gegen hautdurchdringende Würmer bzw. deren Vorstadien erreicht. Während eines längeren Aufenthaltes im Wasser ist der Wirkstoff wiederholt aufzutragen.When using the agents according to the invention, 0.03 to 1 mg, preferably 0.03 to 0.1 mg and particularly preferably 0.04 to 0.06 mg of the active ingredient are generally applied per square centimeter of skin. This provides prophylactic protection against skin-penetrating worms or their pre-stages. The active ingredient must be applied repeatedly during a longer stay in the water.
Die erfindungsgemäßen Mittel werden durch die folgenden Beispiele illustriert ohne sie jedoch einzuschränken.
Biologisches BeispielThe compositions according to the invention are illustrated by the following examples, but without restricting them. Biological example
Wirksamkeit gegen Schistosoma mansoni-CercarienEfficacy against Schistosoma mansoni cercariae
[500 μl/1 Endkonzentration der Wirkstoffe][500 μl / 1 final concentration of the active ingredients]
Zur Infektion wurden Schnecken (Biomphalaria glabrata) mit jeweils 8 Miracidien in in 10 ml Wasser über Nacht inkubiert. Cercarien wurden etwa 6 bis 9 Wochen nach Infektion gewonnen, indem die im Dunkeln gehaltenen Schnecken mit Licht bestrahlt und die danach ausschwärmenden Cercarien innerhalb von 2 Stunden gesammelt wurden.For infection, snails (Biomphalaria glabrata) were incubated with 8 miracidia each in 10 ml of water overnight. Cercariae were obtained about 6 to 9 weeks after infection by irradiating the snails kept in the dark with light and collecting the cercariae after they had swarmed out within 2 hours.
Den Versuchsansätzen wurde soviel Cercarien-haltiges Wasser zugesetzt (1 bzw. 2 ml, siehe unten), daß jeder Ansatz etwa 100 bis 150 Cercarien enthielt.Sufficient water containing cercariae (1 or 2 ml, see below) was added to the test batches so that each batch contained about 100 to 150 cercariae.
5 μl Wirkstoff wurden mit 25 μl PEG300 gründlich vermischt. Anschließend wurde 9 ml Aquarienwasser zugesetzt und der Ansatz heftig geschüttelt. Nach (zeitversetzter) Zugabe von 1 ml Cercarien-Suspension wurde jeweils ab sofort mit der Stereolupe das Überleben der Cercarien beobachtet. Zur Einteilung der Wirksamkeit der Wirkstoffe wurde folgende Einteilung verwendet : 0 = keine Wirkung über die gesamte Versuchsdauer von 120 Minuten; 1 = schwache Wirkung (Cercarien weisen eine stark verringerte Beweglichkeit auf); 2 = gute Wirkung (Cercarien sind nur noch leicht beweglich und gelcrümmt); 3 = volle Wirksamkeit (Cercarien sind vollkommen regungslos)5 μl of active ingredient were thoroughly mixed with 25 μl of PEG300. Then 9 ml of aquarium water was added and the mixture was shaken vigorously. After (delayed) addition of 1 ml of cercariae, the survival of the cercariae was observed with the stereo magnifier. The following classification was used to classify the effectiveness of the active compounds: 0 = no effect over the entire test period of 120 minutes; 1 = weak effect (cercariae have a greatly reduced mobility); 2 = good effect (cercariae are only slightly mobile and curved); 3 = full effectiveness (cercariae are completely motionless)
Bewertung für verschiedene erfindungsgemäße Verbindungen:
Verbindung BewertungEvaluation for various compounds according to the invention: Connection rating
Claims
1. Mittel zur Abwehr von helminthischen Parasiten, gekennzeichnet durch einen Gehalt an mindestens einer Verbindung der Formel (I)1. Agent for defense against helminthic parasites, characterized by a content of at least one compound of the formula (I)
in welcher in which
Y für Wasserstoff, gegebenenfalls substituiertes Alkyl oder für den Rest O-X steht,Y represents hydrogen, optionally substituted alkyl or the radical O-X,
X für Wasserstoff, COR1 COOR12, R13 steht,X represents hydrogen, COR 1 COOR 12 , R 13 ,
R1 für einen gegebenenfalls substituierten Alkyl-, Alkenyl-, Cycloalkyl oder Cycloalkenylrest steht,R 1 represents an optionally substituted alkyl, alkenyl, cycloalkyl or cycloalkenyl radical,
R2, R11, R12 und R13 gleich oder verschieden sind und für gegebenenfalls substituierte Alkyl- oder Alkenylreste stehen,R 2 , R 11 , R 12 and R 13 are identical or different and represent optionally substituted alkyl or alkenyl radicals,
R3 bis R10 gleich oder verschieden sind und für Wasserstoff oder für gegebenenfalls substituierte Alkenylreste stehen und wobei R2 und R3 gemeinsam mit den Atomen, an welche sie gebunden sind auch einen gegebenenfalls substituierten monocyclischen Ring bilden können undR 3 to R 10 are the same or different and represent hydrogen or optionally substituted alkenyl radicals, and where R 2 and R 3 together with the atoms to which they are attached can also form an optionally substituted monocyclic ring and
n und m gleich oder verschieden sind und 0 oder 1 bedeuten, mit der Maßgabe, dass X nicht für Wasserstoff oder R13 steht, wenn n und m für 0 stehen. n and m are the same or different and represent 0 or 1, with the proviso that X is not hydrogen or R 13 if n and m are 0.
2. Mittel zur Abwehr von helminthischen Parasiten gemäß Anspruch 1, gekennzeichnet durch einen Gehalt an mindestens einer Verbindung der Formel (I), in welcher2. Means for defense against helminthic parasites according to claim 1, characterized in that they contain at least one compound of the formula (I) in which
Y für Wasserstoff, d-Ce-Alkyl oder für den Rest O-X steht,Y represents hydrogen, d-Ce-alkyl or the radical O-X,
X für Wasserstoff, COR11 oder R13 steht,X represents hydrogen, COR 1 1 or R 13 ,
R1 für C3-C7-Cycloalkyl, C3-C7-Cycloalkenyl, C1-C2-Alkyl-C3-C7-Cyclo- alkyl, C]-C -Alkyl-C3-C -Cycloalkenyl, wobei die Cycloalkyl- oderR 1 for C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkenyl, C 1 -C 2 alkyl-C 3 -C 7 cycloalkyl, C] -C alkyl-C 3 -C cycloalkenyl , where the cycloalkyl or
Cycloalkenylringe der vorgenannten Reste gegebenenfalls bis zu dreifach durch Ci-Cg-Alkyl oder durch eine Ci-Cg-Dialkylenbrücke substituiert sind oderCycloalkenyl rings of the above radicals are optionally substituted up to three times by Ci-Cg-alkyl or by a Ci-Cg-dialkylene bridge or
R1 für CrC7-Alkyl oder C3-C7-Alkenyl steht,R 1 represents C r C 7 alkyl or C 3 -C 7 alkenyl,
R2, R11, R13 gleich oder verschieden sind und für C^-Cg- Alkyl stehen,R 2 , R 11 , R 13 are the same or different and represent C 1 -C 6 -alkyl,
R3 bis R6 gleich oder verschieden sind und für Wasserstoff oder Cj-Cg- Alkyl stehen, wobei R2 und R3 gemeinsam mit den Atomen, an welche sie gebunden sind, einen 5- oder 6-gliedrigen monocyclischen Ring bilden können undR 3 to R 6 are identical or different and represent hydrogen or Cj-Cg-alkyl, where R 2 and R 3 together with the atoms to which they are attached can form a 5- or 6-membered monocyclic ring and
n für 1 undn for 1 and
m für 0 steht.m stands for 0.
3. Verfahren zur Bekämpfung von parasitischen Helminthen, dadurch gekennzeichnet, dass man Verbindungen der Formel (I) gemäß Anspruch 1 auf Helminthen und/oder ihren Lebensraum einwirken lässt. 3. A method for combating parasitic helminths, characterized in that compounds of the formula (I) according to Claim 1 are allowed to act on helminths and / or their habitat.
4. Verwendung von Verbindungen der Formel (I) gemäß Anspruch 1 zur Bekämpfung von parasitischen Helminthen.4. Use of compounds of formula (I) according to claim 1 for combating parasitic helminths.
5. Verfahren zur Herstellung von Mitteln zur Abwehr von helminthischen Parasiten, dadurch gekennzeichnet, dass man Verbindungen der Formel (I) gemäß Anspruch 1 mit Streckmitteln und/oder oberflächenaktiven Mitteln vermischt. 5. A process for the preparation of agents for defense against helminthic parasites, characterized in that compounds of the formula (I) according to Claim 1 are mixed with extenders and / or surface-active agents.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10032879A DE10032879A1 (en) | 2000-07-06 | 2000-07-06 | Anthelmintics to prevent parasitic infections in humans and animals II |
DE10032879 | 2000-07-06 | ||
PCT/EP2001/007200 WO2002002087A2 (en) | 2000-07-06 | 2001-06-25 | Anthelminthic agents for the prevention of parasitic infections in humans and animals ii |
Publications (1)
Publication Number | Publication Date |
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EP1309320A2 true EP1309320A2 (en) | 2003-05-14 |
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EP01945311A Withdrawn EP1309320A2 (en) | 2000-07-06 | 2001-06-25 | Anthelminthic agents for the prevention of parasitic infections in humans and animals ii |
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US (1) | US20040014813A1 (en) |
EP (1) | EP1309320A2 (en) |
JP (1) | JP2004501959A (en) |
KR (1) | KR20030017542A (en) |
CN (1) | CN1440280A (en) |
AU (1) | AU2001267565A1 (en) |
BR (1) | BR0112369A (en) |
CA (1) | CA2413581A1 (en) |
DE (1) | DE10032879A1 (en) |
HU (1) | HUP0301298A3 (en) |
PL (1) | PL359596A1 (en) |
WO (1) | WO2002002087A2 (en) |
ZA (1) | ZA200300055B (en) |
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DE102006007546A1 (en) * | 2006-02-16 | 2007-08-30 | Saltigo Gmbh | Water-in-oil formulation for arthropod and platelet defenses |
DE102006007549A1 (en) * | 2006-02-16 | 2007-08-30 | Lanxess Deutschland Gmbh | Oil-in-water formulation for arthropod and platelet defenses |
DE102006007547A1 (en) * | 2006-02-16 | 2007-08-30 | Lanxess Deutschland Gmbh | Gel formulation for arthropod and platelet defenses |
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DE3708033A1 (en) * | 1987-03-12 | 1988-09-22 | Bayer Ag | AGENT FOR INSECT AND MITE REVENTION |
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2001
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- 2001-06-25 JP JP2002506709A patent/JP2004501959A/en active Pending
- 2001-06-25 EP EP01945311A patent/EP1309320A2/en not_active Withdrawn
- 2001-06-25 KR KR1020027017199A patent/KR20030017542A/en not_active Application Discontinuation
- 2001-06-25 WO PCT/EP2001/007200 patent/WO2002002087A2/en not_active Application Discontinuation
- 2001-06-25 US US10/311,463 patent/US20040014813A1/en not_active Abandoned
- 2001-06-25 BR BR0112369-6A patent/BR0112369A/en not_active IP Right Cessation
- 2001-06-25 CA CA002413581A patent/CA2413581A1/en not_active Abandoned
- 2001-06-25 PL PL01359596A patent/PL359596A1/en not_active Application Discontinuation
- 2001-06-25 AU AU2001267565A patent/AU2001267565A1/en not_active Abandoned
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PL359596A1 (en) | 2004-08-23 |
US20040014813A1 (en) | 2004-01-22 |
DE10032879A1 (en) | 2002-01-17 |
CA2413581A1 (en) | 2003-01-03 |
CN1440280A (en) | 2003-09-03 |
KR20030017542A (en) | 2003-03-03 |
BR0112369A (en) | 2003-05-13 |
AU2001267565A1 (en) | 2002-01-14 |
WO2002002087A3 (en) | 2002-06-20 |
HUP0301298A3 (en) | 2005-04-28 |
WO2002002087A2 (en) | 2002-01-10 |
HUP0301298A2 (en) | 2003-08-28 |
ZA200300055B (en) | 2004-01-30 |
JP2004501959A (en) | 2004-01-22 |
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