CN110612984B

CN110612984B - Application of cyclopropylimine in oncomelania killing medicine

Info

Publication number: CN110612984B
Application number: CN201910982665.XA
Authority: CN
Inventors: 邢云天; 戴建荣
Original assignee: Jiangsu Institute of Parasitic Diseases
Current assignee: Jiangsu Institute of Parasitic Diseases
Priority date: 2019-10-16
Filing date: 2019-10-16
Publication date: 2021-11-05
Anticipated expiration: 2039-10-16
Also published as: CN110612984A

Abstract

The invention provides an application of cyclopropaneimine in oncomelania killing drugs, belonging to the technical field of schistosomiasis control. The invention uses the active component of the cyclopropane imine to prepare the molluscicide, the molluscicide takes the forms of suspending agent, emulsion and microemulsion, and is applied to killing oncomelania. The usage amount of the cyclopropanimide as the molluscicide active ingredient is 1.00-10.00mg/L, and the soaking and killing time is 24 or 48 hours. Experiments prove that the cyclopropanimide has killing activity on oncomelania, and can be prepared into a molluscicidal preparation to be applied to the field of schistosomiasis control.

Description

Application of cyclopropylimine in oncomelania killing medicine

Technical Field

The invention relates to a new application of cyclopropanimide, belonging to the field of schistosomiasis control.

Background

Schistosomiasis japonica is an infectious parasitic disease which seriously affects the health of people in China, is popular in 74 countries in the world and belongs to zoonosis. According to the WHO estimates that 6 million people worldwide are in a dangerous environment for schistosome infection, of which about 2 million people are infected. The Yangtze river basin and 12 provinces, direct prefectures and autonomous regions in the south of China are popular. Oncomelania hupensis is found to be the only intermediate host of Schistosoma japonicum. Molluscicidal activity is an important link in the control of schistosomiasis japonica.

The method for preventing and treating oncomelania includes environmental oncomelania killing, physical oncomelania killing, biological oncomelania killing, drug oncomelania killing and the like.

The drug has a relatively long molluscacidal effect, can determine the application range according to regions, and is a method for more molluscacidal use. At present, the method for killing snail by using a medicament commonly used at home and abroad is the chemical medicament snail killing. Sodium pentachlorophenate which is popularized and used in the past has good snail killing effect and low price, but has serious harm to human, livestock, aquatic animals and plants and serious environmental pollution, and is forbidden to be used by WHO.

Niclosamide is a chemical molluscicide still used at present, has good drug effect, but the oncomelania obviously climbs away from water after contacting with the drug, reduces the molluscicidal effect, is expensive, has high toxicity to non-target organisms, and influences the popularization and application of the drug.

Cyclopropaneimine, also known as cyclopropanoylamin, ipramine, english name: carpopamid, CAS No.104030-54-8, molecular formula C15H18CL3NO, molecular weight 334.67, pure colorless crystal, with a solubility in water of 1.9mg/l (br) at pH 7 and 20 ℃. The cyclopropanimide is a systemic and protective bactericide, is mainly used for preventing and treating rice blast of rice fields at present, and has no toxic action on rice seedlings under the recommended dosage.

WHO and China always focus on the research of molluscicidal drugs, and the molluscicide with good molluscicidal effect, low toxicity, less pollution and low price is expected to be developed. Therefore, the development of new molluscicides has wide application prospect and huge market value.

Disclosure of Invention

In view of the above-mentioned disadvantages of niclosamide in the prior art, it is an object of the present invention to provide a novel use of a cyclopropylimine for the preparation of molluscicidal drugs.

The inventor proves that the low-dose cyclopropionimide has a killing effect on oncomelania through a large number of screening experiments at the early stage, has the activity of killing the oncomelania as an intermediate host of schistosoma japonicum, and can be prepared into a molluscicide to be applied to the field of prevention and control of schistosomiasis.

If necessary, one or more auxiliary materials acceptable in the dosage form can be added into the molluscicide. The auxiliary materials comprise conventional diluents, fillers, adhesives, wetting agents, absorption promoters, surfactants, adsorption carriers, lubricants and the like in the field of pharmaceutics. The molluscicide taking the cyclopropaneimine as the active ingredient is mainly sprayed to be administrated and can be prepared into various pesticide formulations such as suspending agent, emulsion, microemulsion and the like. The various dosage forms can be prepared according to the conventional method in the field of pesticide preparation.

The invention observes the killing effect of the cyclopropionimine with different dosages on oncomelania, proves that the cyclopropionimine has obvious snail killing effect, and therefore, the cyclopropionimine can be widely applied to the field of schistosome prevention and control.

In order to achieve the above objects and other related objects, the present invention provides use of a cyclopropylimine in the preparation of a oncomelania-killing drug, characterized in that: the molluscicide is prepared by taking the cyclopropaneimine as an active ingredient, and the molluscicide is selected from suspending agents, emulsions, microemulsions and granules.

Preferably, the use amount of the cyclopropanimide for killing oncomelania is 1.00-10.00 mg/L.

Preferably, the use amount of the cyclopropanimidate for killing oncomelania is 10.00mg/L, and the soaking time is 24 or 48 hours.

Preferably, the molluscicide also comprises one or more auxiliary materials acceptable on dosage forms.

Preferably, the adjuvant includes a diluent, a filler, a binder, a wetting agent, an absorption enhancer, a surfactant, an adsorption carrier and a lubricant, which are conventional in the field of pharmaceutical formulation.

The invention has the beneficial effects that: the novel application of the cyclopropanimide is found, and the cyclopropanimide can be used for killing the snails. Simultaneously overcomes the defects of the prior medicine niclosamide, has lower price and lower toxicity to non-target organisms (particularly fishes).

Detailed Description

The following description of the embodiments of the present invention is provided for illustrative purposes, and other advantages and effects of the present invention will become apparent to those skilled in the art from the present disclosure.

EXAMPLE 1 killing of Oncomelania by Cyclopropioneimide

Preparing 6 groups of cyclopropylimide solutions with the concentrations of 10.00, 1.00 and 0.10mg/L, wherein the liquid medicine in each group is 100ml, soaking the oncomelania for 24 hours and 48 hours, pouring out the liquid medicine, washing with clear water, recovering for 48 hours, observing the death and the activity of the oncomelania by a tapping method, and counting; meanwhile, a blank control and a 50% niclosamide ethanolamine salt wettable powder control are set. The detailed results are shown in Table 1.

TABLE 1 Cyclopropionimide Leaching Effect

Example 2 study of acute toxicity of aquatic organisms

And (3) testing the fish species: zebra fish, body length 20 + -2 mm, body weight 0.5 + -0. lg.

The test process comprises the following steps: the drug concentrations were 0.01mg/L, 0.05mg/L, 0.20mg/L, 0.50mg/L, 2mg/L, 20mg/L, 40mg/L, 60mg/L, and 80mg/L, respectively, for 9 groups.

The domestication is carried out for 7 days in the continuously aerated diluted water before the test, and the water quality condition and the lighting condition during the domestication are consistent with the conditions during the test. Feeding is stopped 24h before the test, the death rate during the domestication period is not more than 10%, the water temperature is kept at 23 +/-1 ℃ during the test, the dissolved oxygen content in the test is higher than 60% of the air saturation value, the pH value is 7.0 +/-0.2, the test period is 48h, the poisoning symptoms and the death rate of the tested fish are observed and recorded at any time within 3 to 6h after the test is started, and the poisoning symptoms and the death rate of the tested fish under different concentrations are observed and recorded within 12h, 24h, 36h and 48h after the test is started. The dead fish is judged by tapping the tail part of the fish with glass, and the dead fish is determined if no reaction occurs. The toxicity results of each drug on fish are shown in table 2.

TABLE 2 LC50 value determination of drug toxicity to Zebra fish

The results show that: the LC50 value of the cyclopropylimide at 48h is more than 10mg/L, while the LC50 value of the niclosamide at 48h is only 0.067mg/L, and the administration of niclosamide at a concentration of 0.20mg/L for 1 hour results in almost total death of the fish. It can be seen that the compounds of the present invention have very low toxicity to fish. Therefore, the niclosamide compound is safe to aquatic organisms and is expected to be further researched and developed into a safe and effective niclosamide substitute medicament.

The foregoing embodiments are merely illustrative of the principles and utilities of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or change the above-mentioned embodiments without departing from the spirit and scope of the present invention. Accordingly, it is intended that all equivalent modifications or changes which can be made by those skilled in the art without departing from the spirit and technical spirit of the present invention be covered by the claims of the present invention.

Claims

1. The application of the cyclopropanimide in preparing the oncomelania killing medicine is characterized in that: the molluscicide is prepared by taking cyclopropaneimine as an active ingredient, and the molluscicide is selected from suspending agents, microemulsions and granules; the dosage of the cyclopropanimide as the molluscicide active ingredient is 1.00-10.00 mg/L; the leaching time of the cyclopropionimide as the molluscicide active ingredient is 24 or 48 hours.

2. Use of a cyclopropylimine according to claim 1 in the preparation of a oncomelania killing drug, characterized in that: the molluscicide also comprises one or more excipients acceptable in formulation.

3. Use of a cyclopropylimine according to claim 2 in the preparation of a oncomelania killing drug, characterized in that: the auxiliary materials comprise diluents, fillers, adhesives, wetting agents, absorption promoters, adsorption carriers and lubricants which are conventional in the field of pharmaceutical science.