阅读说明：本技术 一种防治动物外寄生虫病的药物及应用 (Medicine for preventing and treating animal ectoparasitosis and application thereof ) 是由 尚小飞 苗小楼 代立霞 潘虎 张继瑜 李冰 于 2019-12-17 设计创作，主要内容包括：本发明公开了化合物4-甲氧基-2H-色烯-2-酮作为防治动物外寄生虫病药物的用途。所述的4-甲氧基-2H-色烯-2-酮作为杀虫药物与传统的药物相比,具有以下特点和优点：4-甲氧基-2H-色烯-2-酮防治动物外寄生虫病效果好,相较于现有技术中的杀虫剂获得了显著提高；4-甲氧基-2H-色烯-2-酮其毒性低,对环境安全；4-甲氧基香豆素能溶于多种溶剂,易与其它杀动物体外寄生虫成分混配制药,可起到提高杀虫效果的作用。本发明提供了一种较为安全的杀动物外寄生虫药物。(The invention discloses application of a compound 4-methoxy-2H-chromen-2-one as a medicine for preventing and treating animal ectoparasite diseases. Compared with the traditional medicine, the 4-methoxy-2H-chromene-2-ketone as the insecticidal medicine has the following characteristics and advantages: the 4-methoxy-2H-chromene-2-one has good effect of preventing and treating animal ectoparasitosis, and is obviously improved compared with the pesticide in the prior art; 4-methoxy-2H-chromen-2-one has low toxicity and is safe to the environment; the 4-methoxy coumarin can be dissolved in various solvents, is easy to be mixed with other animal ectoparasite killing components for preparing medicines, and can play a role in improving the insecticidal effect. The invention provides a safer drug for killing animal ectoparasites.)

Application of 4-methoxy-2H-chromen-2-one in preparation of medicines for preventing/treating animal ectoparasite diseases is disclosed.

2. The use according to claim 1, wherein the ectoparasites are one or more of fleas, lice, flies, mosquitoes, ticks and mites.

The application of 4-methoxy-2H-chromen-2-one as synergistic agent of animal ectoparasite resisting medicine.

4. The use according to claim 3, wherein the ectoparasites are one or more of ticks, mites, fleas, lice, flies and mosquitoes.

Application of 4-methoxy-2H-chromen-2-one as lead compound of anti-animal ectoparasite drugs.

6. The use according to claim 5, wherein the ectoparasites are one or more of fleas, lice, flies, mosquitoes, ticks and mites.

7. The use according to any one of claims 1 to 6, wherein the 4-methoxy-2H-chromen-2-one is formulated as a powder, an injection, a topical ointment, an emulsion, a spray, with the addition of pharmaceutically acceptable excipients.

Technical Field

The invention belongs to the field of veterinary medicines, and discloses a new application of a 4-methoxy-2H-chromen-2-one compound, in particular to an application of the compound in preventing and treating animal ectoparasitosis.

Background

Animal ectoparasites such as fleas, lice, flies, mosquitoes, ticks, and mites can be infested with many types of animals at all ages, resulting in reduced performance of the affected animals and in decreased quality of the livestock products, and even death. It is reported that the transmission of African swine fever, a virulent infectious disease that severely affects the production of domestic pigs, is inseparable with insects such as ticks as vectors. Meanwhile, the health of human beings is seriously threatened, and 1 to 3 hundred million cases of scabies infection are reported every year in the world. Animal ectoparasitosis not only directly affects the production benefit and healthy development of livestock breeding industry, but also harms related industries such as leather processing and the like, and causes serious economic loss. At present, chemical drugs are still important means for controlling the occurrence of the diseases caused by the external diseases of the animals, such as organic phosphorus, carbamates, pyrethroids and the like, but the problems of drug resistance, drug residues and the like are often generated after long-term use of a large amount of the drugs. Therefore, the development of a high-efficiency, safe and low-toxicity medicament capable of effectively treating animal ectoparasitosis is of great significance.

At present, some medicines for treating animal ectoparasites, such as amido hydroxymethyl coumarins, have been developed to have good acaricidal activity; the methoxy coumarin compounds such as scopoletin and scoparone have good acaricidal activity; coumarin compounds such as imperatorin, isoimperatorin and the like have certain insecticidal activity, but the insecticidal effect of the medicine is not obvious, and the clinical application cannot be met.

4-methoxy-2H-chromen-2-one (4-methoxy-2H-chromen-2-on), CAS: 20280-81-3, molecular formula is C₁₀H₈O₃. The coumarin compound is derived from microorganisms, can be synthesized, has a simple synthesis method, belongs to coumarin compounds, and has less research on the pharmacological and toxicological properties at present. In the invention, the inventor discovers for the first time that the 4-methoxy-2H-chromen-2-one has good insecticidal and acaricidal activity and can be used for preventing and treating animal ectoparasite diseases.

Disclosure of Invention

The invention aims to provide a new application of 4-methoxy-2H-chromen-2-one. The specific technical scheme is as follows:

the invention aims to provide application of 4-methoxy-2H-chromen-2-one in preparation of a medicine for preventing/treating animal ectoparasite diseases.

Preferably, the animal ectoparasite is one or more of tick, mite, flea, louse, fly and mosquito.

Another object of the present invention is to provide the use of 4-methoxy-2H-chromen-2-one as a synergistic agent against animal ectoparasitic agents.

Preferably, the animal ectoparasite is one or more of tick, mite, flea, louse, fly and mosquito.

The invention also aims to provide application of the 4-methoxy-2H-chromen-2-one serving as a lead compound of an anti-parasitic drug.

Preferably, the animal ectoparasite is one or more of tick, mite, flea, louse, fly and mosquito.

Preferably, the 4-methoxy-2H-chromen-2-one is added with pharmaceutically acceptable auxiliary materials to be prepared into powder, injection, external ointment, emulsion, spray and the like.

The medicine of the invention has the beneficial effects that:

the 4-methoxy-2H-chromene-2-one has high-efficiency prevention and treatment effects on animal ectoparasite diseases, and can be used as a new insecticidal lead compound or a synergistic agent for biological reasonable development. Has better control effect on various common animal ectoparasite diseases such as ticks, mites, fleas, lice, flies, mosquitoes and the like. Experiments prove that the lethality of the 4-methoxy-2H-chromene-2-one to the young ticks longicornus is 75.33 +/-3.06%, and is remarkably improved compared with the pesticide in the prior art. And the cure rate of the 4-methoxy-2H-chromene-2-ketone for treating rabbit acariasis is 86.67%, the total effective rate is 100%, and the treatment effect is equivalent to that of the commercially available ivermectin. The 4-methoxy-2H-chromene-2-ketone is simple to synthesize, can be dissolved in various solvents, is easy to be mixed with other acaricidal components for preparing a medicament, plays a role in improving the acaricidal effect, and is suitable for popularization and application.

Detailed Description

The foregoing and other aspects of the present invention will become more apparent from the following detailed description, given by way of example only, for purposes of illustrating the invention. This is not to be construed as limiting the invention.

The experiments disclosed by the invention are not specially explained, and all adopt a conventional method;

the drugs of the present invention are not specifically described, and are commercially available.

Example 1 study of insecticidal Activity of coumarins on Young Lepidium hunger

1. Experimental methods and materials

Collecting Haemaphysalis longicornis hungericornis starving adult ticks, carrying out passage by using New Zealand big ear white rabbits as hosts, and culturing at 27 +/-2 ℃ under the condition that RH is more than or equal to 80%. The test ticks were used only once and then sacrificed with boiling water.

Grouping experiments: 4-methoxy-2H-chromen-2-one, 7-hydroxy-4-methylcoumarin (hydroxymethyl coumarin) group, scopoletin group, imperatorin group, and isoimperatorin group.

The experimental method comprises the following steps: 50 young ticks incubated for 10 days were placed in filter paper bags of 4X 4cm according to the filter paper bag method. After the drug was dissolved in 10% DMSO, 0.8ml of the drug solution was soaked in filter paper coated with young ticks, and the solvent control was 10% DMSO. After 5 minutes, all young ticks were transferred to untreated filter paper bags, sealed, cultured in an incubator (27. + -. 1 ℃ C., RH. gtoreq.80%) for 24h, counted under a microscope for the number of deaths, and considered dead once immobile. The experiment was performed in triplicate.

2. Results of the experiment

TABLE 1 insecticidal Activity of different compounds on Young ticks hunger

Group of	Concentration of	Mortality (%)
			4-methoxy-2H-chromen-2-one group	300μg/mL	75.33±3.06％
7-hydroxy-4-methylcoumarins	300μg/mL	52.00±4.00％
			Scopoletin lactone group	300μg/mL	32.66±3.06％
Scoparone group	300μg/mL	61.33±5.03％
			Imperatorin group	300μg/mL	31.33±3.06％
Isoimperatorin group	300μg/mL	16.00±5.29％
			Solvent control group	--	0.00±0.00

The insecticidal activity of different compounds on young ghrelin ticks is shown in table 1, and it can be seen from table 1 that the highest lethality rate of the 4-methoxy-2H-chromen-2-one group is 75.33 +/-3.06% under the same drug concentration, compared with the 7-hydroxy-4-methylcoumarin group, scopoletin group, imperatorin group, isoimperatorin group and solvent control group, the insecticidal activity of the 4-methoxy-2H-chromen-2-one group is the best. Comparison of the control group of 7-hydroxy-4-methylcoumarin, scopoletin, scoparone, imperatorin and isoimperatorin revealed that the highest lethality of scoparone group was 61.33 ± 5.03%. In order to further verify the insecticidal activity of the 4-methoxy-2H-chromen-2-one, the 4-methoxy-2H-chromen-2-one and scoparone are selected for subsequent mite-killing clinical efficacy research.

EXAMPLE 2 study of the clinical efficacy of acaricidal Agents

1. Experimental groups and dosages

4-methoxy-2H-chromen-2-one drug treatment group: 100 mu g/mL;

the scoparone drug treatment group comprises: 100 mu g/mL;

1% ivermectin group: 100 mu g/mL;

2. experimental methods

New Zealand big-ear white rabbits naturally infected with psoriatic mites are collected from a farm, according to a grading system (table 2) of the conditions of the psoriatic mites clinically infected with rabbits, 45 big-ear white rabbits with similar scores are selected and randomly divided into three groups of 15 rabbits, each group of 15 rabbits is free from other drug treatments and other complications before experiments, and clinically no significant difference exists among the three groups. The 4-methoxy-2H-chromene-2-one drug treatment group and the scoparone drug treatment group spray drugs on the crus of the external auditory canals of the rabbits, and the drugs are respectively administered once every 3 days, 6 days, 9 days, 12 days and 15 days, 2mL for each time, and 5 times, and the ivermectin group is injected according to the drug instruction. Observing the clinical manifestations and health conditions of the rabbits suffering from the acariasis within 15 days, and grading and judging the curative effect according to the diseased situation.

TABLE 2 grading System for clinical itch mite rabbit cases and recovery conditions

3. Results of the experiment

The curative effect of different medicines for treating rabbit acariasis is shown in table 3, and the 4-methoxy-2H-chromene-2-one group obtained from the curative effect for treating rabbit acariasis is 86.67 percent, and the total effective rate is 100 percent; the cure rate of the scoparone group is 60 percent, and the total effective rate is 90 percent; the cure rate and the total effective rate of the 4-methoxy-2H-chromene-2-one group are obviously improved compared with the scoparone group; the cure rate of the ivermectin group is 93.33%, the total effective rate is 100%, the ivermectin is a known effective medicament for treating animal ectoparasites in the field, the 4-methoxy-2H-chromene-2-one group protected by the invention obtains a curative effect equivalent to that of the animal ectoparasites when treating the animal ectoparasites, meanwhile, the commercially available ivermectin is injected and administered, and the administration is complex, while the 4-methoxycoumarin claimed by the invention is prepared into powder, injection, external ointment, emulsion, spray and the like, so that the administration is convenient.

TABLE 3 curative effect of different drugs on rabbit acariasis

In conclusion, the 4-methoxy-2H-chromen-2-one claimed by the invention has high lethality to the young ticks pernicious, can kill other parasites including the young ticks pernicious, such as fleas, lice, flies, mosquitoes and the like, and meanwhile, the cure rate of the 4-methoxy-2H-chromen-2-one claimed by the invention to the rabbit acariasis is equivalent to that of ivermectin, and can be applied to the preparation of medicaments for treating animal ectoparasites.

Finally, it should be noted that: the above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and it will be obvious to those skilled in the art that modifications may be made in the technical solutions described in the above embodiments, or some technical features may be equivalently replaced. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.