WO2007095842A1 - Utilisation d'acides ginkgoliques pour préparer un pesticide biotique destiné à éliminer les escargots et à prévenir la schistomiase - Google Patents

Utilisation d'acides ginkgoliques pour préparer un pesticide biotique destiné à éliminer les escargots et à prévenir la schistomiase Download PDF

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WO2007095842A1
WO2007095842A1 PCT/CN2007/000461 CN2007000461W WO2007095842A1 WO 2007095842 A1 WO2007095842 A1 WO 2007095842A1 CN 2007000461 W CN2007000461 W CN 2007000461W WO 2007095842 A1 WO2007095842 A1 WO 2007095842A1
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Prior art keywords
snail
acid
snails
ginkgolic
killing
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PCT/CN2007/000461
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English (en)
Chinese (zh)
Inventor
Jiahu Pan
Zuohua Mao
Peizhong Yu
Delong Xie
Qi Gao
Xiaohai Pan
Kai Sun
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Fudan University
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Priority claimed from CNB2006100240405A external-priority patent/CN100462006C/zh
Priority claimed from CN2006100276017A external-priority patent/CN101088339B/zh
Application filed by Fudan University filed Critical Fudan University
Publication of WO2007095842A1 publication Critical patent/WO2007095842A1/fr

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/36—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
    • A01N37/38—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids having at least one oxygen or sulfur atom attached to an aromatic ring system
    • A01N37/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids having at least one oxygen or sulfur atom attached to an aromatic ring system having at least one carboxylic group or a thio analogue, or a derivative thereof, and one oxygen or sulfur atom attached to the same aromatic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N65/00—Biocides, pest repellants or attractants, or plant growth regulators containing material from algae, lichens, bryophyta, multi-cellular fungi or plants, or extracts thereof
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the invention belongs to the field of biological pesticides, and relates to a new use of 6-alkylsalicyl ic acids (6-ASAs), commonly known as ginkgolic acids (GA) in the preparation of biological pesticides, and specifically relates to ginkgolic acid.
  • 6-ASAs 6-alkylsalicyl ic acids
  • GA ginkgolic acids
  • the invention also relates to a highly effective and low toxicity acaricidal preparation containing ginkgolic acid. Background technique
  • the genus Corynebacterium is the only intermediate host of schistosomiasis.
  • the snails of the schistosomiasis invade the snail, they can develop into the sputum sputum, which can proliferate thousands of times in the snail, and continuously produce the tail scorpion in the water or moist soil surface, and even infect humans and other animals, so that the schistosomiasis The spread and spread of the disease. Elimination of snails can cut off the transmission of schistosomiasis. Therefore, killing snails is an internationally recognized important measure to prevent schistosomiasis.
  • Schistosomiasis is prevalent in temperate, subtropical, and tropical regions. In 2001, it is estimated that the global population of schistosomiasis is about 200 million people, 600 million people are threatened, and 76 countries are affected, the vast majority of which are developing countries. The disease has seriously harmed the people of these countries. Health and economic development. There are 12 provinces and 418 counties in China with schistosomiasis epidemics, and about 1 million schistosomiasis patients. The total population of the endemic area is about 100 million people, with a snail area of 3787 km 2 .
  • molluscicide is one of the quickest and most effective ways to eliminate or reduce the infection and spread of schistosomiasis.
  • Ginkgo biloba acid is another active ingredient other than flavonoids and lactones in ginkgo, which is found in ginkgo leaves and outer seed coats.
  • Ginkgoic acid (6-hydrocarbylsalicylate) is a class of alkyl or alkenylphenolic compounds.
  • Ginkgo biloba is an important component of ginkgo leaves and their fruits and outer seeds. Ginkgo is one of the oldest species on earth, and it is the "living fossil" left over from the Jurassic. Studies on the existing ginkgo population in China show that its longevity is 2 to 3 thousand years, which is a rare "longevity family" in nature. One of the important reasons for the longevity of ginkgo is that it has significant resistance to common pests and diseases of plants. Ginkgo acid is an important member of its own defense system. Ginkgo biloba is a deciduous tree species. Every year, a large number of ginkgo leaves and outer seed coats degrade and circulate in nature, without damaging the ecological environment. Thus, ginkgolic acid is environmentally compatible and biodegradable.
  • Ginkgo biloba accounts for 1 to 2% of the dry weight of Ginkgo biloba leaves, and accounts for 3 to 5% of Ginkgo biloba exocarp (dry).
  • the amount of ginkgo leaf extract is 200 tons, and the amount of ginkgo acid in the ginkgo leaf extract is about 2. 2%, that is, the total amount of ginkgo acid removed from the ginkgo leaf extract is about 4. 4 tons.
  • the research and development of ginkgolic acid can comprehensively utilize ginkgo leaves and outer seed coats, turning waste into treasure, and generating enormous social and economic benefits.
  • 6-hydrocarbyl salicylic acid is a naturally occurring class of compounds in plants (represented by ginkgo), and there is no report on the activity of killing snails in its biological activity.
  • the object of the present invention is to provide a new use of ginkgolic acid in the preparation of biological pesticides, in particular to the use of ginkgolic acid in the preparation of biological pesticides for killing harmful mollusks, in particular to the preparation of ginkgolic acid for killing snails and preventing schistosomiasis. Use in pesticides.
  • the invention has been confirmed by experiments that ginkgolic acid can effectively kill the only intermediate host of the widely-populated schistosomiasis, snail and ginkgolic acid, which can be used for the prevention and treatment of schistosomiasis.
  • the invention opens up a new application of ginkgolic acid to kill snails and prevent schistosomiasis, and not only can change waste into treasure, but also comprehensively utilize ginkgo leaves, and further prepare novel biological molluscicide to prevent schistosomiasis.
  • the ginkgolic acid (6-hydrocarbyl salicylic acid compound) according to the present invention is an alkyl group or an alkenyl phenolic acid compound, and has a structure of the formula (I), wherein R is a lipid chain and is a main activity for killing snails.
  • the structure of ginkgolic acid is different from known chemical synthetic snail-killing agents or plant-derived snail-killing structures (such as semi-indole, triterpenoids, isoflavones, etc.), which are simple in structure, easy to synthesize or structurally modified.
  • the number of carbon (C) atoms on the R group may be 8 to 20 (C8 to 20); the number of double bonds on the R group may be 0 to 4, such as: C13: 0, C13: 1, etc.;
  • the carbon (C) atom on the group may be substituted by other atoms, such as 0, S, N or a halogen element.
  • the ginkgolic acid is chemically separated from the ginkgo leaf and the ginkgo biloba and its crude extract or pure Obtained in the extract, or recovered from the waste remaining in the extraction process of Ginkgo biloba extract, comprehensively utilized, or obtained from extracts of other parts of the plant containing the compound; or obtained by chemical synthesis , synthesized by salicylic acid as raw material; or further analyzed, identified and controlled by high performance liquid chromatography (HPLC) and other related analytical techniques.
  • HPLC high performance liquid chromatography
  • the drug comprising the compound of the present invention may be a crude extract or a pure extract derived from the leaves, outer seed coats and fruits thereof of ginkgo, or may be derived from extracts of various parts containing the compounds of other plants.
  • the medicament comprising the compound of the present invention can be used alone as a snail-killing agent, or can be used in combination with other snail-killing agents to enhance the snail-killing effect or reduce its toxic side effects and reduce the cost.
  • the pharmaceutical composition comprising the compound of the present invention may be in a solid form such as a powder, a granule, a liposome or the like.
  • the solid carrier can be a non-toxic, biodegradable, hydrophilic or hydrophobic material.
  • the pharmaceutical composition comprising the compound of the present invention may be in a liquid form such as a solution, an emulsion, a suspension or the like.
  • the liquid carrier can be water or a hydrophilic or hydrophobic organic solvent and a mixture thereof in various proportions in water.
  • compositions comprising a compound of the invention can be sprayed onto water or soil containing snails. It can be sprayed once every 3 to 4 days to enhance the killing effect on the snail.
  • the invention provides a high-efficiency and low-toxic composite snail-killing agent containing ginkgolic acid, which is mainly composed of ginkgolic acid, and is composed of niclosamide, copper ions and auxiliary materials in the following weight percentage, ginkgolic acid: 20 ⁇ 50%, Niclosamide: 0.1 to 10%, copper sulfate: 0.01 to 1%, and the remainder is an auxiliary material.
  • the copper ion is a snail-killing synergist which is produced by reacting copper sulfate with sodium hydroxide.
  • the ginkgolic acid-containing composite snail-killing agent of the present invention can be prepared into a microemulsion by a suitable preparation method of three active ingredients.
  • the microemulsion is relatively stable and easy to produce, store, transport and use.
  • the preparation containing the formulation of the preparation of the present invention may be in the form of a concentrated liquid preparation such as a microemulsion, an emulsion or the like, or a concentrated solid preparation such as a powder, a granule, a liposome or the like.
  • the ginkgolic acid-containing composite molluscicide of the present invention is prepared by the following method:
  • the ginkgolic acid and niclosamide are first dissolved in the co-solvent-ethanol according to the following weight percentage, and the non-ionic emulsifier-Tween 80 is added; and the configured 1 equivalent of sodium hydroxide is added to the quantitative copper sulfate. Prepared into a copper hydroxide colloid; then mixed by a high-speed emulsifier and added with water to prepare a microemulsion; or
  • the quantitative niclosamide wettable powder is directly dissolved in water, and the ginkgolic acid is dissolved in ethanol and added to Tween 80, and then the two are mixed with the copper hydroxide colloid by a high-speed emulsifier, and water is added to prepare a microemulsion. .
  • the other is ethanol.
  • the snail killing test is carried out according to the immersion method in the WHO "Snail Preparation Laboratory Final Screening Method".
  • the results showed that the effect of ginkgolic acid on killing snails has the following characteristics compared with niclosamide: (1) Ginkgoic acid can effectively inhibit the snail climbing and prevent it from escaping and killing; (2) Ginkgo biloba kills snails The effect is faster, and the death of the snail mainly occurs within 24 hours.
  • the results of LC50 determination of ginkgolidine killing snails showed that the order of killing snails was: GA-C 13 : o > GA-C 15 : I > GA- C 15 : . ⁇ GA-C n : i > GA- C 17 : 2 .
  • the snail-killing activity was mainly in the former three.
  • the 24-hour LC50 was 13.17 mg/L, 18.57 mg/L, and 26.33 mg/L, respectively.
  • the content of these three in ginkgoic acid was about 70%.
  • the synergistic effect of the body makes the ginkgolic acid achieve a better snail killing effect.
  • the main monomeric compound of ginkgolic acid and the LC50 of guaric acid to kill snails are within the range of the snail-killing agent required by WHO ( ⁇ 100 mg/L).
  • the snail-killing dose of the present invention is from l to 100 mg/L. The dose used will not cause harm to humans and freshwater fish;
  • the compatibility of the snail-clopidogrel wettable powder with ginkgolic acid can produce a synergistic effect, greatly reducing the dosage, and the dosage of niclosamide contained is 10 ⁇ 1000 ug/L.
  • the dose used reduces its toxicity to freshwater fish, meets environmental requirements and reduces costs.
  • the snail-killing agent-copper ion by compatibility with ginkgolic acid and niclosamide, can enhance the inhibition of the snail snail climb rate and increase its killing effect, and the dosage is 1 ⁇ ppm.
  • the dosage used meets economic and environmental requirements.
  • the snail-killing agent of the present invention is subjected to a fish toxicity test according to the "Temporary Regulations for Fish Toxicity Test" formulated by the Yangtze River Fisheries Research Institute, and the results show that there is no obvious toxic effect on freshwater fish.
  • the preparation comprising the snail-killing agent of the present invention may be diluted with water to a suitable concentration at the time of use, and sprayed on the water or soil containing the snail. It can be sprayed once every 3 to 4 days to enhance the killing effect on the snail.
  • Example 1 The effect of ginkgolic acid (C13: 0) component on killing snails
  • the ginkgolic acid (C13: 0) component was purified by the above-mentioned white crystals with a purity of 95%, dissolved in a small amount of absolute ethanol, and diluted with tap water cooled by boiling to different concentrations: 50 mg/L, 25 mg/L, 12.5 mg. /L, 6.25 mg / L 3.13 mg / L (the final concentration of ethanol is ⁇ 0.5%).
  • the niclosamide (produced by Huainan Pharmaceutical Factory) was used as a positive control drug, and the niclosamide ethanolamine wettable powder was diluted with boiling water cooled by boiling to the desired concentration. At the same time, tap water cooled after boiling was used as a control with 0.5% ethanol solution.
  • Snail taken from the epidemic area of schistosomiasis in Yueyang, Hunan. Male snails were removed by group eschar and cultured in the laboratory for 72 hours. The snails with a screwing age of 8 to 9 are selected for use.
  • the UV detection wavelength was 311 nra, for the above ginkgolic acid ( C15: 1)
  • the component is subjected to identification and is compared with the standard for purity determination.
  • the purity of the component of the ginkgolic acid (C15:1) was 60.63%.
  • the above obtained ginkgolic acid (C15: l) component was dissolved in a small amount of absolute ethanol, and diluted with tap water cooled by boiling to different concentrations: 50 mg / L, 25 mg / L, 12.5 mg / L, 6.25 mg / L 3.13mg/L (the final concentration of ethanol is ⁇ 0.5%) o
  • the niclosamide (produced by Huainan Pharmaceutical Factory) is the positive control drug, and the niclosamide ethanolamine wettable powder is diluted with the tap water cooled by boiling. To the desired concentration. At the same time, tap water cooled after boiling was used as a control with 0.5% ethanol solution.
  • Snail taken from the epidemic area of schistosomiasis in Yueyang, Hunan.
  • the male snails were removed by the group sputum method and cultured in the laboratory for 72 hours.
  • the snails with a screwing age of 8 to 9 are selected for use.
  • the total ginkgolic acid content of the crude extract of Ginkgo biloba exocarp was determined by the above RP-HPLC method to be 5.46%.
  • Snail taken from the epidemic area of schistosomiasis in Yueyang, Hunan. Male snails were removed by group eschar and cultured in the laboratory for 72 hours. The snails with a screwing age of 8 to 9 are selected for use.
  • the purity of the ginkgolic acid (C15:1) component was determined to be 60.63% by HPLC.
  • the ginkgolic acid (C15: l) component is dissolved in a small amount of absolute ethanol, diluted with tap water cooled by boiling, mixed with niclosamide ethanolamine powder which has been prepared by boiling water cooled, and then boiled.
  • the post-cooled tap water is diluted to a final concentration of 10 mg/L and 0.5 mg/L, respectively, of the ginkgolic acid (C15:1) component and the niclosamide ethanolamine wettable powder.
  • the niclosamide (produced by Huainan Pharmaceutical Factory) was used as a positive control drug, and the niclosamide ethanolamine wettable powder was diluted to the desired concentration with tap water cooled by boiling. At the same time, tap water cooled after boiling was used as a control with 0.5% ethanol solution.
  • Snail taken from the epidemic area of schistosomiasis in Yueyang, Hunan. The male snails were removed by the group sputum method, and the snails were selected to be snails in the laboratory for 72 hours.
  • Example 5 Decoupling effect of ginkgolic acid on oxidative phosphorylation of snail mitochondria
  • ginkgolic acid (C15: 1) The purity of the ginkgolic acid (C15: 1 ) component was determined to be 60.63% by HPLC.
  • the ginkgolic acid (C15: 1 ) component was dissolved in a small amount of absolute ethanol, and diluted with tap water cooled by boiling, and used.
  • a group of energetic adult snails were taken and the male snails were removed by group sputum method and cultured in the laboratory for 72 hours. Select a screw with a screwing age of 8 to 9 to be used as a screw.
  • the shell was broken by a broken snail method, and the head and foot of the snail were taken, and the mitochondria were prepared by centrifugation according to the literature method.
  • the mitochondrial respiratory control rate (RCR) was determined by oxygen electrode method, and the change of phosphorus and the activity of ATPase were measured by the malachite green method to study the cleavage of mitochondrial oxidative phosphorylation by ginkgolic acid (C15: 1 ) component. Joint action.
  • the ginkgolic acid (C15: 1) component dose-dependently increased the content of inorganic phosphorus and ATPase in the dose range (10 mg/L, 20 mg/L, 40 mg/L). , reducing its RCR, indicating that the ginkgolic acid (C15: 1) component has a good decoupling effect on oxidative phosphorylation of the snail mitochondria.
  • each 6-hydrocarbyl salicylic acid monomer was carried out on a Water HPLC preparative column chromatography system.
  • the total extract of 6-hydrocarbyl salicylic acid was dissolved in petroleum ether and applied to an Elit Kromasil C18 column (4.6 x 300 mm, 5 um).
  • the obtained eluate containing each component was concentrated and dried.
  • the purity of each 6-hydrocarbyl salicylic acid monomer prepared in this way can be more than 95%.
  • the mass spectrum was obtained by negative ion mode and recorded in the ⁇ ?/250 ⁇ 450 interval.
  • the capillary column temperature was 300 e C and the gas flow rate was 10 L/min.
  • the injection voltage in the negative ESI mode is 3500 V. See Figure 6-6 for the mass spectrometric identification of each monomeric compound in the total hydrocarbyl salicylate extract.
  • 6-hydrocarbyl salicylic acid In addition to the above-mentioned total extraction of 6-hydrocarbyl salicylic acid by direct extraction from an organic solvent, other routes can be used to extract and prepare a total extract of 6-hydrocarbyl salicylic acid.
  • the acidity of 6-hydrocarbylsalicylic acid is extracted by the following alkali extraction method.
  • Example 8 Determination of the activity of each monomeric compound of 6-hydrocarbyl salicylic acid to kill snails
  • Each of the 6-hydrocarbyl salicylic acid monomer compounds is isolated and purified by the above method, all of which are white crystals with a purity of >95%, dissolved in a small amount of absolute ethanol (final concentration ⁇ 0.5%), and added with a small amount of emulsifier or cosolvent. (Tween-80, final ethanol concentration ⁇ 1%), and then diluted to different concentrations with tap water cooled after boiling: 50mg / L, 25mg / L, 12.5mg / L, 6.25mg / L, 3.13mg / L.
  • the niclosamide ethanolamine wettable powder (manufactured by Huainan Pharmaceutical Factory) was used as a positive control drug, and it was diluted with boiling water cooled by boiling to the desired concentration. At the same time, tap water cooled after boiling was used as a control with 0.5% ethanol solution.
  • Snail collected from the epidemic area of schistosomiasis in Yueyang County, Hunan province. The male snails were removed by the group sputum method, and the snails with the snail age of 8 to 9 were selected in the laboratory for 72 ho.
  • the total extract of 6-hydrocarbyl salicylic acid can be obtained by extraction and separation by the above method, and its purity is >90%.
  • Snail collected from the epidemic area of schistosomiasis in Yueyang County, Hunan province. The male snails were removed by the group sputum method, and the snails were selected to be snails in the laboratory for 72 ho.
  • the total extract of 6-hydrocarbyl salicylic acid prepared above is dissolved in a small amount of absolute ethanol (final concentration ⁇ 0.5%), and a small amount of emulsifier or cosolvent (Tween-80, final concentration of ethanol ⁇ 1%) is added.
  • a small amount of emulsifier or cosolvent Tween-80, final concentration of ethanol ⁇ 1%
  • the niclosamide ethanolamine wettable powder manufactured by Huainan Pharmaceutical Factory
  • was used as a positive control drug was used as diluted with boiled and cooled tap water to the desired concentration.
  • tap water cooled after boiling was used as a control with 0.5% ethanol solution.
  • Snail collected from the epidemic area of schistosomiasis in Yueyang County, Hunan province. The male snails were removed by the group sputum method, and the snails with the snail age of 8 to 9 were selected in the laboratory for 72 ho.
  • the composite snail-killing agent is mainly composed of the above-mentioned 6-hydrocarbyl salicylic acid total extract, and is scientifically compatible with niclosamide, copper ions and other auxiliary materials according to the following weight percentages to form a new composite snail-killing agent:
  • 6 -hydrocarbyl salicylic acid 10 ⁇ 60%, niclosamide: 0. 1 ⁇ 20%, copper ion: 0. 01 ⁇ 5%, the rest are auxiliary solvents such as cosolvents, emulsifiers and stabilizers.
  • the 6-hydrocarbyl salicylic acid is a total extract of 6-hydrocarbyl salicylic acid having a relatively constant content ratio of each monomer compound; niclosamide is a wettable powder; copper ion is a snail-killing synergist, ie A copper hydroxide colloid produced by the reaction of copper sulfate with sodium hydroxide.
  • the total extract of 6-hydrocarbyl salicylic acid is dissolved in a small amount of absolute ethanol (final concentration ⁇ 0.5%), and a small amount of emulsifier or cosolvent (Tween-80, final concentration ⁇ 1%) is added, and chlorine is added.
  • emulsifier or cosolvent Titramide, copper hydroxide colloid and stabilizer are then thoroughly mixed by an idler emulsifier or a homomixer, and water is added to prepare a 0/W type microemulsion or emulsion.
  • This method produces a high concentration of stock solution for production, storage, transportation and use. When used, it can be diluted with water to the desired concentration.
  • Example 12 Synergistic snail killing effect of total extract of 6-hydrocarbyl salicylic acid and niclosamide
  • 6-hydrocarbyl salicylic acid total extract is dissolved in a small amount of absolute ethanol, added with a suitable emulsifier, by high-speed emulsification Prepare the emulsion (the final concentration of ethanol is ⁇ 0.1%).
  • the niclosamide wettable powder is formulated into a stock solution using tap water cooled after boiling. According to the ratio of Table 3, two liquids were separated and prepared into test liquids containing different concentrations of 6-hydrocarbyl salicylic acid total extract and niclosamide. At the same time, the tap water cooled after boiling was used as a blank control.
  • the snail-killing test was carried out according to the soaking method in the WHO "Spermicide Laboratory Final Screening Method".
  • Snail From the epidemic area of schistosomiasis in Yueyang, Hunan. The male snails were removed by the group sputum method, and the snails with a snail age of 8 to 9 were selected in the laboratory for 72 o.
  • 6-ASAs (mg/L) 0 1.25 2.5 5 10 20 40 0
  • the total extract of the quantitative 6-based salicylic acid is dissolved in the co-solvent-ethanol, and the niclosamide and the emulsifier-Tween 80 (1/10 of the amount of ethanol) are added; the other 1 equivalent of sodium hydroxide is configured.
  • tap water cooled after boiling was used as a blank control.
  • the snail-killing test was carried out according to the immersion method in the WHO "Spiral Laboratory Final Screening Method". Snail: collected from the epidemic area of schistosomiasis in Yueyang, Hunan. The male snails were removed by the group sputum method, and 72 snails were selected in the laboratory culture for 8 ⁇ 9 rotation.
  • Table 4 shows the synergistic effect of copper ions on the killing of snails by 6-hydrocarbyl salicylic acid and niclosamide in the preparation of the present invention.
  • 6-ASAs (mg L) 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 0 0
  • Niclosamide (ug/L) 50 50 50 50 50 0 .0
  • a composite microemulsion 4000 mL containing 6-hydrocarbyl salicylic acid (5 mg/L), niclosamide (50 ug/L), and copper ions (6 ppm) was prepared as described above. Take 50 mL from it for culture of snails. The rest is used to culture freshwater fish - red carp fry. The fish toxicity test was carried out according to the “Temporary Regulations for Fish Toxicity Test” formulated by the Yangtze River Fisheries Research Institute.
  • Snail From the epidemic area of schistosomiasis in Yueyang, Hunan. The male snails were removed by the group sputum method, and the snails with the snail age of 8 to 9 were selected in the laboratory culture. Add 30 ml of the above solution to the 25 ml beaker (ie, fill up to the cup), put 10 snails, and cover the nylon mesh to prevent the snail from crawling out. For the snails immersed in the corresponding liquid and placed in the beaker on the horizontal tabletop, observe and record the death of the snails at room temperature (22+ ⁇ ). Observe the activity by acupuncture combined with tapping method. Determine if it is dead.

Abstract

L'invention se rapporte à une nouvelle utilisation d'acides 6-alkyl-salicyliques connus sous le nom d'acides ginkgoliques pour préparer un pesticide biotique. L'invention concerne en particulier l'utilisation d'acides ginkgoliques pour éliminer les escargots et prévenir la schistomiase. L'invention permet de tirer le meilleur parti des feuilles de ginkgo. L'invention a également trait à un agent d'élimination des escargots contenant des acides ginkgoliques, qui présente ainsi une activité élevée et une faible toxicité. L'invention concerne en outre une composition pesticide destinée à éliminer les escargots, qui contient de 20 à 50% d'acides ginkgoliques, de 0,1 à 10% de niclosamide, de 0,01 à 1% de sulfate de cuivre et des additifs. La composition selon l'invention permet d'éliminer efficacement les escargots Oncomelania, qui sont les seuls vecteurs de la schistomiase en Chine, ce qui permet de lutter contre la schistomiase.
PCT/CN2007/000461 2006-02-21 2007-02-15 Utilisation d'acides ginkgoliques pour préparer un pesticide biotique destiné à éliminer les escargots et à prévenir la schistomiase WO2007095842A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
CN200610024040.5 2006-02-21
CNB2006100240405A CN100462006C (zh) 2006-02-21 2006-02-21 银杏酸在制备杀灭钉螺、防止血吸虫病的生物农药中的用途
CN200610027601.7 2006-06-12
CN2006100276017A CN101088339B (zh) 2006-06-12 2006-06-12 一种含银杏酸的复合杀螺剂及其制备方法

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CN103766332A (zh) * 2014-01-26 2014-05-07 江苏艾津农化有限责任公司 一种可用于喷施的新型环保杀钉螺颗粒剂及其制备方法
CN103766332B (zh) * 2014-01-26 2016-05-18 江苏艾津农化有限责任公司 一种可用于喷施的新型环保杀钉螺颗粒剂及其制备方法
CN105265248A (zh) * 2015-11-02 2016-01-27 湖南理工学院 生态消除钉螺种群的机理
CN109418332A (zh) * 2017-08-29 2019-03-05 湖北金海潮科技有限公司 一种复合植物灭螺剂及其制备方法和应用
CN110419531A (zh) * 2019-08-19 2019-11-08 临沂大学 一种银杏酚酸可湿性粉剂
CN110839644A (zh) * 2019-11-27 2020-02-28 中南林业科技大学 一种提高银杏外种皮银杏酸有效经济产量的方法
CN113826646A (zh) * 2021-08-15 2021-12-24 江苏小禾生物技术研究院有限公司 一种银杏酚酸溶液剂及制备方法
CN114288705A (zh) * 2021-11-19 2022-04-08 广东青云山药业有限公司 一种从银杏叶提取物中去除银杏酸的方法
CN114288705B (zh) * 2021-11-19 2023-11-17 广东青云山药业有限公司 一种从银杏叶提取物中去除银杏酸的方法
CN117814265B (zh) * 2024-03-01 2024-05-17 临沂大学 一种微生物发酵银杏外种皮的方法及其应用

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