WO2020007018A1 - 一种食品级灭蚊幼制剂及其制备方法和应用 - Google Patents

一种食品级灭蚊幼制剂及其制备方法和应用 Download PDF

Info

Publication number
WO2020007018A1
WO2020007018A1 PCT/CN2019/000127 CN2019000127W WO2020007018A1 WO 2020007018 A1 WO2020007018 A1 WO 2020007018A1 CN 2019000127 W CN2019000127 W CN 2019000127W WO 2020007018 A1 WO2020007018 A1 WO 2020007018A1
Authority
WO
WIPO (PCT)
Prior art keywords
mosquito
isothiocyanate
propylene
preparation
polyoxyethylene ether
Prior art date
Application number
PCT/CN2019/000127
Other languages
English (en)
French (fr)
Inventor
王渊
王雪平
刘起勇
卢金星
王毅
程璟侠
孟凤霞
李兴
任东生
徐海军
张永光
冯帅
刘小波
Original Assignee
王渊
王雪平
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by 王渊, 王雪平 filed Critical 王渊
Publication of WO2020007018A1 publication Critical patent/WO2020007018A1/zh

Links

Classifications

    • 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
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/46—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=C=S groups
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/02—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
    • A01N25/04—Dispersions, emulsions, suspoemulsions, suspension concentrates or gels
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
    • A01N25/10—Macromolecular compounds
    • 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
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/12—Powders or granules

Definitions

  • the invention relates to a mosquito killing larva preparation and a preparation method and application thereof, in particular to a mosquito killing preparation prepared with a food additive propylene isothiocyanate and a preparation method and application thereof.
  • the invention belongs to the field of biomedical technology.
  • mosquitoes are important pests that spread various infectious diseases such as dengue fever, malaria, yellow fever, filariasis, and encephalitis. According to incomplete statistics, the number of deaths caused by mosquito-transmitted diseases every year in the world is about 7 to 1 million. Among them, malaria is a mosquito-borne infectious disease that causes major health risks to tropical and subtropical regions. Another important mosquito-borne disease is the dengue virus, which is transmitted by Aedes aegypti and infects about 100 million people each year, mainly in Latin America and Asia. Mosquito-borne diseases have been on the rise in the United States in recent years.
  • Eastern Equine Encephalitis Virus is another arbovirus transmitted by mosquitoes, which has also caused illness in humans in the United States, Central and South America. EEE infections are characterized by convulsions and coma, causing death in about half of patients. In addition, the large-scale use of chemical mosquito killers has led to a rapid increase in mosquito resistance. Therefore, there is an urgent need for safer, more environmentally friendly, more effective, and non-resistant agents to protect humans from mosquito-borne diseases.
  • Dithiphos is currently the most commonly used mosquito killer preparation in the world. Due to potential or long-term risks to the environment and water bodies, countries such as the European Union have added dithiphos to their restricted or banned lists.
  • pyrethroid pesticides have also been included in the list of prohibited or restricted use by the EU and other countries.
  • the Canadian Pest Management Agency (PMRA) proposed in November 2017 to ban certain uses of the pyrethroid insecticide permethrin.
  • lambda-cyhalothrin was designated by the European Union as a candidate for substitution due to its high toxicity.
  • PMRA proposed a ban on the use of the pyrethroid insecticide, lambda-cyhalothrin, in all food and feed crops, and ceased its use indoors.
  • the application number is 201510394924.9, and the invention name is "a preparation for mosquito larvae and its preparation and application”.
  • the active larvae-killing compound used is tert-butylphenol, which is toxic to aquatic organisms. Or have adverse effects.
  • the invention name of "sustained mosquito juvenile slow release agent”
  • most of the active substances used are toxic chemical pesticides.
  • the carrier used is glass beads that are not easily degradable, and Bt has a limited effect on mosquito larvae.
  • the application number is 201310419640.1, and the Chinese patent application for the invention name is "matrine plant-derived insecticidal EC" (mosquito killer).
  • the preparation process is complicated, the application cost is high, and the effect is insufficient.
  • Propyl isothiocyanate (abbreviated as AITC), English name Allyl isothiocyanate, chemical formula C 4 H 5 NS, molecular weight 99.15, melting point -80 ° C, boiling point 151-153 ° C, density 1.013, flash point 46 ° C, CAS number 57-06 -7.
  • Propylene isothiocyanate also known as mustard oil or horseradish, is a popular condiment, and has been listed in the food additive catalog by more than 100 countries.
  • the Chinese standard is GB 29980-2013 "National Food Safety Standard Food Additives" Allyl isothiocyanate.
  • the US FDA has clear guidelines for the application of propylene isothiocyanate.
  • FEMA (mg / kg): soft drinks 0.02 to 0.50; cold drinks 0.50; candy 0.50; baked goods 5.2. Moderate limit (FDA-172.515, 2000).
  • the patent application number for greenhouse vegetable disinfection is 201610431130.X "a Shed disinfection method”
  • patent number 200810112497.0 a horseradish capsule and its application “for soil disinfection
  • patent application number 201510757165.8 a horseradish with silica as a carrier
  • Sustained microcapsule sustained-release agent and preparation method thereof the patent number for food preservatives is 201310238688.2” a mustard oil nanoemulsion and a preparation method thereof ", and the like.
  • the applicant of the present invention has found and proved for the first time that the lethal rate of propylene isothiocyanate with a content of 5-50 ppm to mosquitoes can reach 40-100%, and its safety, efficacy and cost are better than dithion. .
  • the present invention is of great significance to reduce the number of mosquito young populations and protect the ecological environment.
  • the purpose of the present invention is to provide a food-grade allyl isothiocyanate mosquito-repellent young preparation and a preparation method and application thereof, which are used to solve the problems of insufficient safety and drug resistance of the chemical mosquito-repellent young preparation.
  • the present invention adopts the following technical means:
  • the present invention proposes for the first time the use of propylene isothiocyanate in the preparation of mosquito-killing young preparations.
  • the propylene isothiocyanate is food-grade propylene isothiocyanate, which meets the requirements of China GB299801-2013 "Food Safety Standard Food Additive Allyl Isothiocyanate", and the effective content is ⁇ 98.0 %.
  • the effective concentration of the mosquito-killing larva of isopropyl cyanate is 5-50 ppm.
  • the present invention also proposes a food-grade mosquito killer preparation, which uses propylene isothiocyanate as an active ingredient of the mosquito killer larva.
  • the mosquito-killing young preparation further contains an emulsifier and a carrier.
  • the carrier is microporous starch or micro-silica powder, and preferably, the particle size of the micro-silica powder is 400-800 mesh.
  • the carrier used in the present invention is preferably microporous starch; in consideration of stability or durability, the present invention is preferably 400 mesh micro-silica powder.
  • the anti-mosquito juvenile preparation is composed of the following weight percentages of each raw material:
  • the emulsifier is AS02-30 sodium lauroyl sarcosinate, potassium monododecyl phosphate, alkylphenol polyoxyethylene ether (OP-10), isooctanol polyoxyethylene ether Phosphate, nonylphenol polyoxyethylene ether, nonylphenol polyoxyethylene ether phosphate, polyoxyethylene ether, sodium lauryl sulfate, calcium dodecylbenzenesulfonate, tea saponin, ligninsulfonic acid Sodium, calcium lignosulfonate, sodium dodecylbenzenesulfonate, alcohol ether carboxylate AEC-9, vegetable polyoxyethylene ether, Tween 80, glycol esters, propylene glycol esters, and polyethylene glycols
  • the emulsifier is AS02-30 sodium lauroyl sarcosinate, alkylphenol polyoxyethylene ether (OP-10), tea
  • the plant-type polyoxyethylene ether includes NSF-10E polyoxyethylene ether, NSF-7 polyoxyethylene ether, NSF-9 polyoxyethylene ether, NSF-10 polyoxyethylene ether, and NSF-20 Polyoxyethylene ether.
  • microporous starch also known as porous starch
  • microporous starch is a natural polymer material. It is safe and non-toxic. It has a honeycomb porous structure with a pore size of 1-2 ⁇ m. The pore volume accounts for about 50% of the particle volume.
  • the drug improves the stability of the drug and has a slow-release effect.
  • micro-silica powder also called micro-powder silica gel
  • micro-powder silica gel is a white powdery inorganic chemical product, non-toxic, odorless, non-flammable, non-explosive, non-volatile, non-corrosive, large pore volume, strong surface activity, and stable chemical properties. It has the function of absorbing and embedding drugs, and is produced by Guangzhou Xinxian Metallurgical Chemical Co., Ltd.
  • propylene isothiocyanate product with a content of less than 5% is produced according to the formula of the present invention, it is suitable for preparing powders; if the propylene isothiocyanate product with a content of more than 5% is produced according to the formula of the present invention, Suitable for preparing emulsion products.
  • the content and dosage form of propylene isothiocyanate in the preparation of the mosquito-killing young preparation, can be adjusted according to the requirements given in the present invention, and products with different contents and different dosage forms can be prepared.
  • the product has high content, good water solubility, can be arbitrarily diluted, and has a large dilution factor, and can be sold as raw materials.
  • a 40% by weight acrylic isothiocyanate mosquito-killing young anhydrous emulsion is prepared. Using 40kg of propylene isothiocyanate, 40kg of emulsifier, and 20kg of micro silicon powder, mix the weighed propylene isothiocyanate, emulsifier, and micro silicon powder and pump it into a high-pressure homogenizer through a liquid pump. Working pressure and feed pressure, homogeneous, can press propylene isothiocyanate into the pores of micro-silica powder, and make 100kg of emulsion with 40% propylene isothiocyanate content, the product content is high, the dilution factor Large, easy to use, good water solubility, can be sold as raw materials. Before use, the 40% propylene isothiocyanate emulsion is diluted to 5-50 ppm with water and sprayed on the surface of the water body to quickly kill mosquito larvae.
  • a powder product By adjusting the raw material formula and the mixing ratio given by the present invention, a powder product can also be produced.
  • Preparation method (1) firstly mixing propylene isothiocyanate and propylene glycol fatty acid ester emulsifier; (2) putting microporous starch into a common pulverizer and starting up; (3) under stirring state, isolating The liquid mixture of propylene thiocyanate and propylene glycol fatty acid ester is slowly added to the pulverizer equipped with microporous starch, so that propylene isothiocyanate and propylene glycol fatty acid ester are uniformly brought into contact with, adsorbed on, and filled with microporous starch.
  • the pulverizer continues to work for 20 to 40 minutes to make the material more uniform, and then the machine is stopped, discharged, and vacuum-packed to obtain the microporous starch loaded with 5% isothiocyanate of the present invention.
  • Mosquito powder After the liquid mixture is completed, the pulverizer continues to work for 20 to 40 minutes to make the material more uniform, and then the machine is stopped, discharged, and vacuum-packed to obtain the microporous starch loaded with 5% isothiocyanate of the present invention.
  • Mosquito powder Mosquito powder.
  • Another example preparing a microsilica powder containing 1% isopropyl thiocyanate mosquito killer powder with a weight percentage content of 1%.
  • Preparation method (1) first mixing isopropyl cyanocyanate and tea saponin emulsifier; (2) put 400 mesh micro silicon powder into a common pulverizer and start up; (3) under stirring state, The liquid mixture of propylene isothiocyanate and tea saponin is slowly added to the pulverizer equipped with micro silicon powder, so that the propylene isothiocyanate and tea saponin are uniformly contacted and adsorbed with the microporous starch. After the liquid mixture, the pulverizer continues to mix for 20-40 minutes to make the material more uniform, and then the machine is stopped, discharged, and vacuum-packed to obtain the microporous starch loaded with 1% isothiocyanate in the invention.
  • Mosquito powder The powder has better stability and persistence than microporous starch, and the disadvantage is that the production cost is slightly higher.
  • the present invention also provides a method for preparing the mosquito-killing young preparation, comprising the following steps:
  • mosquito juvenile formulation is an emulsion:
  • the preferred working pressure of the high-pressure homogenizer is 60 to 200 MPa, the more preferred working pressure is 80 to 120 MPa, the feed pressure is 0.1 to 2 MPa, preferably 0.8 MPa, and the homogenization time is 10 to 50 min;
  • the preparation process and features of the invention are that the isopropyl cyanate is forced into the pores of microporous starch or microsilica powder by the internal pressure of a high-pressure homogenizer, so as to embed, stabilize, store and relax The role of interpretation.
  • Acrylic isothiocyanate mosquito-repellent emulsion obtained by high-pressure homogenization mechanism, transparent, homogeneous, no suspension and precipitation, no water, easy to dissolve in water, and slowly release isopropyl thiocyanate, mosquito-killing Young effect is fast.
  • the present invention also proposes the use of the mosquito-killing preparation for treating mosquito-killing, wherein, preferably, the mosquito-killing includes Aedes, Culex, Egypt Aedes aegypti, Anopheles, Anophelesannulipes, Armigeres, Ayurakitia, Bironella, Borichinda , Chagasia, Coquillettidia, Culex quinquefasciatus, Culex annulirostris, Culiseta, Ficalbia, Tendrobium Haemagogus, Schumannia, Hodgesia, Kimia, Malaya, Mansonia, Mimomyia, Straight Orthopodomyia, Lepidoptera, Sabethes, Topomyia, Toxorhynchites, Trichoprosopon, Triptereroides, and Aedes (Udaya) Mosquito.
  • the mosquito-killing includes Aedes, Culex, Egypt Aedes
  • the mosquito-killing young preparation having a content of 1 to 40% of propylene isothiocyanate prepared by the present invention is a high-concentration masterbatch and cannot be used directly.
  • the concentration of propylene isothiocyanate should be diluted in the range of 5-50 ppm, and then spread on the place where mosquitoes are young, preferably diluted with water, talc and / or corn cob powder.
  • the content of propylene isothiocyanate at 0.005% (50ppm) is 12 hours, and the lethal rate to mosquito larvae can reach 99-100%; the content of propylene isothiocyanate at 0.0025% (25ppm) is 12 hours, the lethal rate to mosquito larvae can reach 99 to 100%; the content of propylene isothiocyanate at 0.0005% (5ppm), 12 hours, the lethal rate to mosquito larvae can reach 90 to 100%.
  • the content of propylene isothiocyanate is 0.00025% (2.5 ppm). After 12 hours of action, the lethal rate to mosquitoes is 40 to 70%. However, the reproducibility is not good. Therefore, the present invention limits propylene isothiocyanate.
  • the minimum effective concentration for use is 5 ppm.
  • the method for evaluating the efficacy of the propylene isothiocyanate anti-mosquito juvenile preparation according to the present invention is:
  • the auxiliary materials used include emulsifiers and carriers, all adopting the corresponding product technical standards provided by the enterprise.
  • the present invention provides a new technical approach for reducing the number of mosquito young populations and solving the problem of drug resistance caused by chemical mosquito repellents.
  • the liquid mixture of propylene isothiocyanate and propylene glycol fatty acid ester is slowly added to a pulverizer equipped with microporous starch to make propylene isothiocyanate and propylene glycol fatty acid ester.
  • the microporous starch is uniformly contacted and adsorbed.
  • the pulverizer continues to mix for 20-40 minutes to make the material more uniform, and then the machine is stopped, discharged, and vacuum-packed to prepare the microporous starch of the present invention.
  • the 5% (w / w) propylene isothiocyanate mosquito killer powder is loaded.
  • the preparation method is simple and the use and storage are convenient.
  • the average particle size of the 25% propylene isothiocyanate emulsion was 199 nm as measured by a laser particle size analyzer.
  • the preparation of mosquito-killing preparations of propylene isothiocyanate and the preparation method and application thereof are provided by the inventor.
  • the inventors have given seven different examples, which explain the preparation of propylene isothiocyanate according to the present invention.
  • Mosquito juvenile preparation and preparation method and application thereof within the scope of the formulation, ratio, high-pressure homogenization process, and pulverization process of the present invention, propylene isothiocyanate mosquito killing formulations with different contents, different carriers, and different emulsifiers were trial-produced.
  • the present invention emphasizes that The best use concentration of propylene isothiocyanate raw material to kill mosquito is 5-50ppm.
  • mosquito larvae were cultured at a temperature of 26 ⁇ 1 ° C, a relative humidity of 70% ⁇ 10%, and a photoperiod of L / D: 12h / 12h. Mosquito larvae with strong vitality and uniform body size were selected.
  • the mortality of the mosquito larvae can reach 90 to 100% 12 hours after dosing.
  • control agent add 1g 1% dithion phosphate particles to a beaker of 25mL dechlorinated water, and put 30 viable and consistent 3rd-instar larvae in the beaker. 12 hours after dosing, the death of Aedes albopictus and Culex mosquitoes Rates can reach 99 to 100%.
  • each pond From the wild breeding ponds provided by Shanxi Badun Environmental Protection Technology Research Institute, each pond has an area of 1 m 2 and a water depth of 20 cm. There are sufficient 2 to 3 instar Aedes and Culex mosquitoes in the pond.
  • the control agent used 1% dithion phosphate particles (produced by Abe, Germany), 1g per square meter, artificially spread, sinking to the bottom of the water, the mosquito mortality rate was 80% after 12 hours, and reached 99% after 24 hours.
  • 0.005% concentration (50ppm) of isothiocyanate has a reliable and rapid killing effect on mosquito larvae such as Culex and Aedes, and the change of the carrier and emulsifier affects the performance of propylene isothiocyanate. The effect is not affected.
  • the present invention measured the indoor and field drug efficacy of Examples 3-7 and other examples not listed.
  • a large number of experimental studies and tests have proved that as long as the use concentration of propylene isothiocyanate is 5 Within the range of ⁇ 50ppm, proper adjustment of the formulation and ratio within the range described in the present invention, especially adjustment or replacement of different emulsifiers or carriers, will not affect the mosquito killing effect and the final purpose of the present invention.
  • the embodiments of the present invention describe the entire technology in a specific and detailed manner, and therefore, it is helpful for those skilled in the art or non-professionals to understand the present invention.
  • the present invention can be easily prepared by those skilled in the art or non-skilled persons without departing from the present invention's discovery, application, and the like. , And can also make a number of deformation or improvement products, including solid, powder, microcapsules, suspensions and other products of different dosage forms, these deformations or improvements belong to the scope of protection of the present invention.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • Agronomy & Crop Science (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Toxicology (AREA)
  • Chemical & Material Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

一种食品级灭蚊幼制剂及其制备方法和应用。所述的灭蚊幼制剂中的有效成分为异硫氰酸丙烯酯，含量为5～50ppm的异硫氰酸丙烯酯对蚊幼的致死率可达90～100％，而且其安全性、药效和使用成本优于双硫磷。所述的灭蚊幼制剂由以下重量百分比的各原料组成：异硫氰酸丙烯酯1～40％，乳化剂2～40％，载体20～97％。一种制备食品级异硫氰酸丙烯酯灭蚊幼制剂的方法，包括高压均质工艺。实验证明，用水将所述的灭蚊幼制剂稀释至异硫氰酸丙烯酯浓度为5～50ppm，喷于水体表面，可快速杀灭蚊幼虫。对减少蚊幼种群数量和保护生态环境具有非常重要的意义。

Description

一种食品级灭蚊幼制剂及其制备方法和应用 技术领域
本发明涉及一种灭蚊幼虫制剂及其制备方法和应用，特别涉及一种用食品添加剂异硫氰酸丙烯制备的灭蚊幼制剂及其制备方法和应用，本发明属于生物医药技术领域。
背景技术
众所周知，蚊子是传播登革热、疟疾、黄热病、丝虫病、脑炎等多种传染病的重要害虫，据不完全统计，全球每年由蚊传播疾病造成的死亡人数大约为75～100万。其中，疟疾是蚊媒传染病的一种，给热带和亚热带地区造成重大的健康隐患。另外一种重要的蚊媒传染病是登革热病毒，由埃及伊蚊传播，每年感染一亿人左右，主要在拉丁美洲和亚洲。蚊媒传播疾病在美国近年处于上升态势。从1999年纽约州首次报道人类感染以来，西尼罗河病毒已经逐步地向南和向西移动，目前在美国本土所有的州都有检出记录。东方马脑炎病毒(EEE)是另一种由蚊传播的虫媒病毒，其也造成了美国以及中美和南美人体的患病。EEE感染的特征为抽搐和昏迷，导致大约一半患者的死亡。除外，大量使用化学灭蚊剂，导致蚊虫的抗药性在急剧增长，因此，全球急需更安全、更环保、更有效、无抗性的药剂保护人类免受蚊虫传染病的侵害。
中国的中药至今已有数千年的历史，为人类做出了重要的贡献，其中，包括众所周知的青蒿素，为治疗由蚊虫叮咬引起的疟疾传染病发挥了重要作用，由此，青蒿素的发明人屠呦呦荣获诺贝尔国际奖。如果，我们能够发明一种新的、无抗药性的、可替代双硫磷的食品级灭蚊幼制剂，那么，我们就希望从根源上减少成蚊的种群数量，这对控制蚊媒传染病和保护生态环境具有非常重要的意义。
目前，国内外已有数种类型的灭蚊剂，多数为低毒类化学品，但是，低毒并不等于无毒，包括双硫磷和菊酯类灭蚊剂，如果长时间使用，易对人体或环境造成远期或不明的危害，包括抗药性的问题，因此引起了欧盟等发达国家的高度关注。
双硫磷(灭幼剂)，4，4′-双(O，O-二甲基硫代磷酰氧基)苯硫醚，别称替美福司，化学式C 16H 20O 6P 2S 3，分子量466.4689，CAS号3383-96-8。白色结晶固体，杀虫作用广谱。急性经口毒性：大鼠LD 50 1000mg/kg；小鼠LD 50 223mg/kg。
双硫磷是目前全球应用最普遍的一种灭蚊幼制剂，由于对环境和水体有潜在或远期的风险，因此，欧盟等国家已将双硫磷列入限制或禁用名单。
菊酯类杀虫剂同样因为存在潜在的风险，同样被欧盟等国列入禁止或限制使用目录。其中，加拿大有害生物管理局(PMRA)于2017年11月建议禁止拟除虫菊酯杀虫剂氯菊酯的某些用途。2015年，高效氯氟氰菊酯因为毒性高等原因被欧盟指定为候选被替代物质。2017年，PMRA提出禁止将拟除虫菊酯类杀虫剂高效氯氟氰菊酯用于所有食品和饲料作物，并停止在住宅室内使用。2013年，欧盟在对杀虫剂进行审查后，联苯菊酯的杀虫杀螨剂非农用途被淘汰。
另外，申请号为201510394924.9，发明名称为“一种用于灭蚊幼虫的制剂及其制备和应用”的中国专利申请中，所用灭幼蚊活性物为叔丁基苯酚类化合物，对水生生物有毒或有不良影响。申请号为87104588，发明名称为“灭蚊幼缓释剂”的中国专利申请中，所用活性物多为有毒的化学杀虫剂。申请号为201310733631.X，发明名称为“一种杀灭蚊子幼虫的苏云金杆菌制剂及其制备方法”的中国专利申请中，所用载体为不易降解的玻璃微珠，且Bt对蚊幼虫作用有限。申请号为201310419640.1，发明名称为“苦参碱植物源杀虫乳油”(灭蚊幼剂)的中国专利申请，其制备工艺复杂，应用成本高，效果不足。
综上所述，化学灭蚊剂可以快速有效地控制有害昆虫，同时也会对环境产生多种多样的副作用。随着全球对于化学品给公众健康和环境带来的危险认知日益提高，天然化合物正逐渐成为有害化学品的替代品。其中，美国环境保护局已经采取立法手段将某些天然化合物或高安全的食品原料划为“环境安全化合物(杀虫剂)”，从而保护这些环境安全化合物的使用不受政府规章的限制。(注：通常所说的“环境安全化合物”是指对生态环境的影响有限或不造成危害的化合物。)
根据国内外现有灭蚊幼剂存在的安全性和环保性的不足，特别是双硫磷和菊酯类杀虫剂已被欧盟等国列入限制或禁用名单，因此，研究能够替代双硫磷等有害灭蚊剂显得刻不容缓，同时，对减少蚊媒传染病和保护生态环境有着极为重要的意义。
异硫氰酸丙烯酯(简称AITC)，英文名Allyl isothiocyanate，化学式C 4H 5NS，分子量99.15，熔点-80℃，沸点151～153℃，密度1.013，闪点46℃，CAS号57-06-7。异硫氰酸丙烯酯又称芥末油或辣根素，是人们普遍喜好的调味品，并被100多个国家列入食品添加剂目录中，中国标准为GB 29980-2013《食品安全国家标准食品添加剂异硫氰酸烯丙酯》。另外，美国FDA对异硫氰酸丙烯酯的应用有明确 的限量指导，FEMA(mg/kg)：软饮料0.02～0.50；冷饮0.50；糖果0.50；焙烤食品5.2。适度为限(FDA-172.515，2000)。
异硫氰酸丙烯酯除用于调味品外，在农业杀虫、食品保鲜、医疗、医药方面的应用研究也非常活跃，比如用于温室大棚蔬菜消毒的专利申请号为201610431130.X“一种棚室消毒方法”，用于土壤消毒的专利号为200810112497.0“一种辣根素胶囊剂及其应用”，用于土壤消毒的专利申请号为201510757165.8“一种以二氧化硅为载体的辣根素微囊缓释剂及其制备方法”，用于食品保鲜剂的专利号为201310238688.2“一种芥末油纳米乳及其制备方法”，等等。
异硫氰酸丙烯酯的应用研究与用途虽然广泛，但是，至今未见异硫氰酸丙烯酯用于灭蚊幼的报道。
本发明申请人首次发现并证明，含量为5～50ppm的异硫氰酸丙烯酯，对蚊幼的致死率可达40～100％，其安全性、药效、使用成本均优于双硫磷。同时，本发明的提出对减少蚊幼种群数量和生态环境的保护具有非常重要的意义。
发明内容
本发明的目的在于提供一种食品级异硫氰酸烯丙酯灭蚊幼制剂及其制备方法和应用，用于解决化学灭蚊幼制剂存在的安全性不足和抗药性问题。
为了达到上述目的，本发明采用了以下技术手段：
本发明首次提出了异硫氰酸丙烯酯在制备灭蚊幼制剂中的用途。
其中，优选的，所述的异硫氰酸丙烯酯是食品级异硫氰酸丙烯酯，符合中国GB299801-2013《食品安全标准食品添加剂异硫氰酸烯丙酯》标准要求，有效含量≥98.0％。
其中，优选的，所述的异硫氰酸丙烯酯的灭蚊幼的有效浓度为5～50ppm。
进一步的，本发明还提出了一种食品级灭蚊幼制剂，将异硫氰酸丙烯酯作为灭蚊幼虫的有效成分。
其中，优选的，所述的灭蚊幼制剂中，还含有乳化剂和载体。
其中，优选的，所述的灭蚊幼制剂中，所述载体为微孔淀粉或微硅粉，优选的，所述的微硅粉的粒径为400～800目。考虑到应用成本的问题，本发明所用载体优选微孔淀粉；考虑到稳定性或持效性的问题，本发明则优选400目的微硅粉。
其中，优选的，所述的灭蚊幼制剂由以下重量百分比的各原料组成：
异硫氰酸丙烯酯 1～40％
乳化剂  2～40％
载体    20～97％
其中，优选的，所述的乳化剂为AS02-30月桂酰肌氨酸钠、单十二烷基磷酸酯钾、烷基酚聚氧乙烯醚(OP-10)、异辛醇聚氧乙烯醚磷酸酯、壬基酚聚氧乙烯醚、壬基酚聚氧乙烯醚磷酸酯、聚氧乙烯醚、十二烷基硫酸钠、十二烷基苯磺酸钙、茶皂素、木质素磺酸钠、木质素磺酸钙、十二烷基苯磺酸钠、醇醚羧酸盐AEC-9、植物型聚氧乙烯醚、吐温80、乙二醇酯、丙二醇酯以及聚乙二醇的一种或几种的混合，优选的，所述的乳化剂为AS02-30月桂酰肌氨酸钠、烷基酚聚氧乙烯醚(OP-10)、茶皂素、聚乙二醇、NSF-10E聚氧乙烯醚，更优选为AS02-30月桂酰肌氨酸钠。
其中，优选的，所述的植物型聚氧乙烯醚包括NSF-10E聚氧乙烯醚、NSF-7聚氧乙烯醚、NSF-9聚氧乙烯醚、NSF-10聚氧乙烯醚以及NSF-20聚氧乙烯醚。
本发明配方中所述或使用的载体，可以是微孔淀粉，也可以是微硅粉。其中，微孔淀粉，又名多孔淀粉，是一种天然高分子材料，安全无毒，具有蜂窝状多孔结构，孔径1～2μm，孔的容积占颗粒体积的50％左右，能吸附和包埋药物，提高药物的稳定性，并具有缓释作用。
所述的微硅粉，又称微粉硅胶，是一种白色粉末状的无机化工产品，无毒、无味、不燃、不爆、不挥发、无腐蚀、孔容大、表面活性强，化学性质稳定，具有吸附和包埋药物的作用，由广州市新稀冶金化工有限公司生产。
值得说明的是，通过调整本发明提出的灭蚊幼配方、配比，不但可以生产不同含量的异硫氰酸丙烯酯灭蚊幼乳液，包括1％、5％、20％、40％重量百分比含量的异硫氰酸丙烯酯，而且，还可以生产不同载体、不同含量异硫氰酸丙烯酯的粉剂和无水乳液产品。
需要说明的是，如果按本发明配方生产含量在5％以下的异硫氰酸丙烯酯产品，适合于制备粉剂；如果按本发明配方生产含量在5％以上异硫氰酸丙烯酯的产品，适合于制备乳液型产品。
在本发明中，所述的灭蚊幼制剂制备，异硫氰酸丙烯酯的含量和剂型可根据需要，在本发明给出的配方范围内调整，可以制得含量不同、剂型不同的产品，包括1～5％异硫氰酸丙烯酯的粉剂和5～40％异硫氰酸丙烯酯的无水乳液。因为异硫氰酸丙烯酯的使用浓度非常的低(5～50ppm)，而且用水可任意稀释，1％含量的异硫氰酸丙烯酯，完全可以作为母料商品生产和销售。使用前，只需用水将异硫氰酸丙烯酯稀释至5～50ppm即可，储存、使用、运输极为方便。总之，只要不违背本 发明提出的异硫氰酸丙烯酯的使用浓度(5～50ppm)，任何含量的调整或剂型的改变，均不会影响本发明的灭蚊虫效果以及最终目的。
举例：制备重量百分比含量为20％的异硫氰酸丙烯酯灭蚊幼乳液。称取20kg异硫氰酸丙烯酯、20kg乳化剂、60kg微孔淀粉(载体)，将称取的异硫氰酸丙烯酯、乳化剂、微孔淀粉混合，通过液体泵泵入高压均质机内，选择合适的工作压力以及进料压力，均质，可将异硫氰酸丙烯酯压入微孔淀粉孔隙中，制得100kg含量为20％的异硫氰酸丙烯酯无水乳液，该产品含量高，水溶性好，可任意稀释，稀释倍数大，可作为原料出售。使用前，用水将20％含量的异硫氰酸丙烯酯无水乳液稀释至5～50ppm浓度，喷于水体表面，即可快速杀灭蚊幼虫。
再例：制备重量百分比含量为40％的异硫氰酸丙烯酯灭蚊幼无水乳液。采用40kg异硫氰酸丙烯酯、40kg乳化剂、20kg微硅粉，将称取的异硫氰酸丙烯酯、乳化剂、微硅粉混合，通过液体泵泵入高压均质机内，选择合适的工作压力以及进料压力，均质，可将异硫氰酸丙烯酯压入微硅粉孔隙中，制得100kg异硫氰酸丙烯酯含量为40％的乳液，所制产品含量高，稀释倍数大，使用简单，水溶性好，可作为原料出售。使用前，用水将40％含量的异硫氰酸丙烯酯乳液稀释至5～50ppm浓度，喷于水体表面，即可快速杀灭蚊幼虫。
通过上述两个高含量异硫氰酸丙烯酯灭蚊幼无水乳液的制备，不难看出，一个浓度为20％，一个浓度为40％，改变或变化载体和含量，并不影响本发明的使用效果。
通过调整本发明给出的原料配方、配比，还可以生产出粉剂产品。
举例：制备微硅粉负载重量百分比含量为5％的异硫氰酸丙烯酯灭蚊幼粉剂。
称取5kg异硫氰酸丙烯酯、5kg丙二醇脂肪酸酯乳化剂(市售商品)、90kg微孔淀粉(辽宁立达生物科技有限公司生产)，备用。
制备方法：(1)先将异硫氰酸丙烯酯和丙二醇脂肪酸酯乳化剂混合；(2)将微孔淀粉放入普通粉碎机内，开机；(3)在搅拌的状态下，将异硫氰酸丙烯酯和丙二醇脂肪酸酯的液体混合物，缓慢加入到装有微孔淀粉的粉碎机内，使异硫氰酸丙烯酯和丙二醇脂肪酸酯与微孔淀粉均匀接触、吸附，加注完液体混合物后，粉碎机继续工作20～40min，使物料更加均匀，然后停机，出料，真空包装，即可制得本发明所述的微孔淀粉负载5％的异硫氰酸丙烯酯灭蚊幼粉剂。
再例：制备微硅粉负载重量百分比含量为1％的异硫氰酸丙烯酯灭蚊幼粉剂。
称取1kg异硫氰酸丙烯酯灭蚊幼剂、2kg茶皂素乳化剂(市售商品)和97kg 400 目微硅粉载体(由广州市新稀冶金化工有限公司生产)，备用。
制备方法：(1)先将异硫氰酸丙烯酯和茶皂素乳化剂混合；(2)将400目微硅粉放入普通粉碎机内，开机；(3)在搅拌的状态下，将异硫氰酸丙烯酯和茶皂素的液体混合物，缓慢加入到装有微硅粉的粉碎机内，使异硫氰酸丙烯酯和茶皂素与微孔淀粉均匀接触、吸附，加注完液体混合物后，粉碎机继续混合20～40min，使物料更加均匀，然后停机，出料，真空包装，即可制得本发明所述的微孔淀粉负载1％的异硫氰酸丙烯酯的灭蚊幼粉剂。该粉剂的稳定性和持效性好于微孔淀粉，不足之处是生产成本略高。
更进一步的，本发明还提出了一种制备所述的灭蚊幼制剂的方法，包括以下步骤：
当所述的灭蚊幼制剂为乳液时：
(1)按照以下重量百分比分别称取各原料，备用；
异硫氰酸丙烯酯 1～40％
乳化剂         2～40％
载体           20～97％
(2)将称取的异硫氰酸丙烯酯、乳化剂、载体混合，通过液体泵泵入高压均质机内，选择合适的工作压力以及进料压力，均质，即可制得含有异硫氰酸丙烯酯的灭蚊幼乳液；
其中，优选的高压均质机的工作压力为60～200MPa，更优选的工作压力为80～120MPa，进料压力为0.1～2MPa，优选0.8MPa，均质时间为10～50min；
当所述的灭蚊幼制剂为粉剂时：
(1)按照以下重量百分比分别称取各原料，备用；
异硫氰酸丙烯酯 1～40％
乳化剂         2～40％
载体           20～97％
(2)将异硫氰酸丙烯酯和乳化剂混合；
(3)将载体放入普通粉碎机内，开机；
(4)在搅拌的状态下，将异硫氰酸丙烯酯和乳化剂的液体混合物，缓慢加入到装有载体的粉碎机内，使异硫氰酸丙烯酯和乳化剂与载体均匀接触、吸附，加注完液体混合物后，粉碎机继续工作20～40min，然后停机，出料，真空包装，即可制得异硫氰酸丙烯酯灭蚊幼粉剂。
本发明的制备工艺和特点，在于借助高压均质机的内压作用，将异硫氰酸丙烯酯强制压入微孔淀粉或微硅粉的孔隙中，起到包埋、稳定、存储和缓释的作用。经高压均质机制得的异硫氰酸丙烯酯灭蚊幼乳液，外观透明、均质、无悬浮和沉淀，不含水，水中易自行溶解，并可缓慢释放异硫氰酸丙烯酯，灭蚊幼作用快。
更进一步，本发明还提出了所述的灭蚊幼制剂在治理蚊幼中的用途，其中，优选的，所述的蚊幼包括伊蚊属(Aedes)、库蚊属(Culex)、埃及伊蚊(Aedes aegypti)、按蚊属(Anopheles)、环须按蚊(Anophelesannulipes)、阿蚊属(Armigeres)、艾蚊属(Ayurakitia)、伯罗按蚊属(Bironella)、鲍蚊属(Borichinda)、恰氏蚊属(Chagasia)、轲蚊属(Coquillettidia)、致倦库蚊(Culex quinquefasciatus)、环纹库蚊(Culex annulirostris)、脉毛蚊属(Culiseta)、费蚊属(Ficalbia)、趋血蚊属(Haemagogus)、领蚊属(Heizmannia)、霍蚊属(Hodgesia)、金蚊属(Kimia)、钩蚊属(Malaya)、曼蚊属(Mansonia)、小蚊属(Mimomyia)、直脚蚊属(Orthopodomyia)、鳞蚊属、煞蚊属(Sabethes)、土蚊属(Topomyia)、巨蚊属(Toxorhynchites)、前毛蚊属(Trichoprosopon)、杵蚊属(Tripteroides)以及尤蚊属(Udaya)蚊幼。
本发明制备得到的异硫氰酸丙烯酯含量为1～40％的灭蚊幼制剂为高浓度母料，不可直接使用。使用前，需稀释异硫氰酸丙烯酯浓度为5～50ppm范围内，然后再撒布于有蚊幼的地方，优选采用水、滑石粉和/或玉米芯粉进行稀释。
室内实验结果表明，异硫氰酸丙烯酯的使用浓度与灭蚊幼的速率成正比。
其中，含量为0.005％(50ppm)的异硫氰酸丙烯酯，作用12h，对蚊幼的致死率即可达99～100％；含量为0.0025％(25ppm)的异硫氰酸丙烯酯，作用12h，对蚊幼的致死率可达99～100％；含量为0.0005％(5ppm)的异硫氰酸丙烯酯，作用12h，对蚊幼的致死率可达90～100％。含量为0.00025％(2.5ppm)的异硫氰酸丙烯酯，作用12h，对蚊幼的致死率达40～70％，但是，重现性不好，因此，本发明限定异硫氰酸丙烯酯的最低使用有效浓度为5ppm。
本发明所述异硫氰酸丙烯酯灭蚊幼制剂的药效评价方法是：
(1)室内试验方法
采用世界卫生组织(WHO)推荐的药液浸养法或中国国家南方农药创制中心生测SOP中的浸虫法。
(2)野外现场试验
依据中国GB/T 31711-2015《卫生杀虫剂现场药效测定与评价 杀蚊幼剂》标准。
(3)灭蚊幼原料(异硫氰酸丙烯酯)的标准
采用中国GB 29980-2013《食品安全国家标准食品添加剂异硫氰酸烯丙酯》标准。
(4)辅料标准
所用辅料包括乳化剂和载体，均采用企业提供的相应产品技术标准。
相较于现有技术，本发明的有益效果是：
(1)本发明申请人首次发现和证明，食品级异硫氰酸丙烯酯在5～50ppm的使用浓度下，对蚊幼虫具有可靠的灭杀作用，并具有食品级的安全性和低于双硫磷的使用成本。
(2)异硫氰酸丙烯酯来源容易，可以从植物中提取，也可以化学合成，均可满足中国国家GB 29980-2013的标准要求。
(3)本发明的提出，为减少蚊幼种群数量和解决化学灭蚊剂产生的抗药性问题提供了新的技术途径。
具体实施方式
下面结合具体实施例来进一步说明本发明的特点，同时，随着实施例与方法的描述，将有助于对本发明进行更详细、更清楚地了解。但是，这些实施例仅是范例性的，并不对本发明的范围构成任何限制。本领域技术人员应该理解的是，在不偏离本发明的精神和范围下，可以对本发明技术方案的细节和形式进行修改或替换，但这些修改和替换均落入本发明的保护范围内。
实施例1 40％(w/w)含量的异硫氰酸丙烯酯灭蚊幼乳液(母料)的制备
(1)称取40kg含量为98％的异硫氰酸丙烯酯(平乡县天邦调味食品有限公司生产)，备用；称取40kg OP-10烷基酚聚氧乙烯醚乳化剂(江苏省海安石油化工厂生产)，备用；称取20kg微孔淀粉载体(辽宁立达生物科技有限公司生产)，备用。
(2)将称好的异硫氰酸丙烯酯、OP-10烷基酚聚氧乙烯醚和微孔淀粉放入不锈钢搅拌机内进行预混合，然后用液体泵将混合物泵入诺泽流体科技(上海)有限公司生产的高压均质机内，设定工作压力为80MPa，进料压力为0.15MPa，开机均质20min，即可制得含量为40％(w/w)的异硫氰酸丙烯酯灭蚊幼乳液。
实施例2 20％(w/w)含量的异硫氰酸丙烯酯灭蚊幼乳液(母料)的制备
(1)称取20kg含量为98％的异硫氰酸丙烯酯(平乡县天邦调味食品有限公司生产)，备用；称取20kg OP-10烷基酚聚氧乙烯醚乳化剂(江苏省海安石油化工厂生产)，备用；称取60kg 400目微硅粉(广州市新稀冶金化工有限公司生产)，备用。
(2)将称好的异硫氰酸丙烯酯、OP-10烷基酚聚氧乙烯醚和微硅粉放入不锈钢搅拌机内进行预混合，然后用液体泵将混合物泵入诺泽流体科技(上海)有限公司生产的高压均质机内，设定工作压力为80MPa，进料压力为0.15MPa，开机均质20min，即可制得含量为20％(w/w)的异硫氰酸丙烯酯灭蚊幼乳液。所得产品因含有微硅粉，稳定性较微孔淀粉好，可用水任意稀释，对环境和人畜无危害。
实施例3 5％(w/w)的异硫氰酸丙烯酯灭蚊幼粉剂(母料)的制备
(1)称取5kg含量为98％的异硫氰酸丙烯酯、5kg丙二醇脂肪酸酯乳化剂(市售商品)、90kg微孔淀粉，备用。
(2)先将异硫氰酸丙烯酯和丙二醇脂肪酸酯乳化剂混合；
(3)将微孔淀粉放入普通粉碎机内，开机；
(4)在搅拌的状态下，将异硫氰酸丙烯酯和丙二醇脂肪酸酯的液体混合物，缓慢加入到装有微孔淀粉的粉碎机内，使异硫氰酸丙烯酯和丙二醇脂肪酸酯与微孔淀粉均匀接触、吸附，加注完液体混合物后，粉碎机继续混合20～40min，使物料更加均匀，然后停机，出料，真空包装，即可制得本发明所述的微孔淀粉负载5％(w/w)的异硫氰酸丙烯酯灭蚊幼粉剂，该制备方法简单，使用和存储方便。
实施例4 1％(w/w)的异硫氰酸丙烯酯灭蚊幼粉剂(母料)的制备
(1)称取1kg含量为98％的异硫氰酸丙烯酯、2kg茶皂素(市售食品)、97kg800目微硅粉载体，备用。
(2)先将异硫氰酸丙烯酯和茶皂素乳化剂混合；
(3)将800目微硅粉放入普通粉碎机内，开机；
(4)在搅拌的状态下，将异硫氰酸丙烯酯和茶皂素的液体混合物，缓慢加入到装有微硅粉的粉碎机内，使异硫氰酸丙烯酯和茶皂素与微硅粉均匀接触、吸附，加注完液体混合物后，使粉碎机继续工作20～40min，停机，出料，真空包装，即可制备出微硅粉负载1％(w/w)的异硫氰酸丙烯酯灭蚊幼粉剂。
实施例5 20％(w/w)的异硫氰酸丙烯酯灭蚊幼乳液(母料)的制备
(1)称取20kg含量为98％的异硫氰酸丙烯酯；称取30kg吐温80乳化剂(市售食品)；称取50kg微孔淀粉载体，备用。
(2)将称取的异硫氰酸丙烯酯、吐温80乳化剂、微孔淀粉放入不锈钢储料桶内预混合，用液体泵泵入诺泽流体科技(上海)有限公司生产的高压均质机内，设定工作压力为90MPa，进料压力为0.2MPa，开机均质25min，即可制得含量为20％(w/w)的异硫氰酸丙烯酯灭蚊幼乳液。所制产品外观透明，均质、水溶性好、稳定，使用和存储方便。
实施例6 25％(w/w)的异硫氰酸丙烯酯灭蚊幼乳液(母料)的制备
(1)称取25kg含量为98％的异硫氰酸丙烯酯；称取30kg茶皂素乳化剂(市售食品)；称取45kg微孔淀粉，备用。
(2)将称取的异硫氰酸丙烯酯、茶皂素、微孔淀粉放入不锈钢储料桶内预混合，通过液体泵将预混料泵入诺泽流体科技(上海)有限公司生产的高压均质机内，设定工作压力为120MPa，进料压力为0.4MPa，开机均质25min，即可制得含量为25％(w/w)的异硫氰酸丙烯酯乳液。所制产品外观清澈，无悬浮和沉淀、水中易溶解，使用和存储方便。
经激光粒度仪测得25％含量异硫氰酸丙烯酯的乳液平均粒径为199nm。
实施例7 30％(w/w)的异硫氰酸丙烯酯灭蚊幼乳液(母料)的制备
(1)称取30kg含量为98％的异硫氰酸丙烯酯；称取40kg氨基酸类表面活性剂AS02-30月桂酰肌氨酸钠(市售商品)；称取30kg微孔淀粉载体，备用。
(2)将称取的异硫氰酸丙烯酯、AS02-30月桂酰肌氨酸钠、微孔淀粉放入不锈钢储料桶内预混合，用液体泵将预混料泵入诺泽流体科技(上海)有限公司生产的高压均质机内，设定工作压力为120MPa，进料压力为0.2MPa，开机均质35min，即可制得含量为30％(w/w)的异硫氰酸丙烯酯灭蚊幼乳液。所制产品水溶性好，投加到水中后，易产生泡沫，具有延迟药效的作用。
实施例8 异硫氰酸丙烯酯灭蚊幼药效的测定
根据本发明提出的异硫氰酸丙烯酯制备灭蚊幼制剂及其制备方法与应用，发明人给出了7个不同的实施例，详细说明了本发明提出的异硫氰酸丙烯酯制备灭蚊幼 制剂及其制备方法与应用。其中，在本发明配方、配比和高压均质工艺及粉碎工艺的范围内，试制了不同含量、不同载体、不同乳化剂的异硫氰酸丙烯酯灭蚊幼制剂，同时，本发明强调了异硫氰酸丙烯酯原料灭蚊幼的最佳使用浓度为5～50ppm。鉴于不同实施例中所用原料相同、使用浓度相同、应用目标相同，因此，采用统一的药效测定方法显得非常必要，下面以实施例1和2所制的40％和20％含量的异硫氰酸丙烯酯乳液为例，说明灭蚊幼的效果评价方法与测定结果。
一.药效的测定方法
1.室内药效的测定
1.1方法
采用世界卫生组织(WHO)推荐的药液浸养法或国家南方农药创制中心生测SOP中的浸虫法。
1.2供试的蚊幼
由山西巴盾环境保护技术研究所提供，包括白纹伊蚊和库蚊。受试的蚊幼在温度26±1℃，相对湿度70％±10％，光周期为L/D：12h/12h的条件下培养，选用2～3龄活力强、体形大小一致的蚊幼虫。
1.3试验步骤
(1)称取实施例1所制含量为40％(w/w)的异硫氰酸丙烯酯乳液2g或称取实施例2所制含量为20％(w/w)的异硫氰酸丙烯酯乳液4.7g，滴入放有14mL去氯离子自来水的烧杯中，混合，得到含量为5％(w/w)的异硫氰酸丙烯酯溶液。
(2)称取2g含量为5％(w/w)的异硫氰酸丙烯酯乳液，滴入放有18mL去氯离子自来水的烧杯中，混合，即得到含量为0.5％(w/w)的异硫氰酸丙烯酯溶液。
(3)取4个50mL烧杯，编号为1、2、3、4，往烧杯中各加入25mL去氯离子自来水，并各引入30头活力健壮、大小一致的3龄白纹伊蚊或库蚊幼虫。
(4)用微量移液枪分别吸取25μL、12.5μL 5％(w/w)的异硫氰酸丙烯酯溶液，分别加入1、2号烧杯，用微量移液枪分别吸取25μL、12.5μL 0.5％(w/w)的异硫氰酸丙烯酯溶液，分别加入3、4号烧杯，这样，1-4号烧杯中异硫氰酸丙烯酯的终浓度分别为0.005％(50ppm)、0.0025％(25ppm)、0.0005％(5ppm)、0.00025％(2.5ppm)，轻微晃动各烧杯，使药液均匀分布在水中。
每个浓度处理设3组重复，包括异硫氰酸丙烯酯试验组、空白对照和1％双硫磷颗粒剂对照。
1.4试验结果
当烧杯水内异硫氰酸丙烯酯终浓度为0.005％(w/w，50ppm)，加药后12h，蚊幼的死亡率达99～100％。
当烧杯水内异硫氰酸丙烯酯终浓度为0.0025％(w/w，25ppm)，加药后12h，蚊幼的死亡率达99～100％。
当烧杯水内异硫氰酸丙烯酯终浓度为0.0005％(w/w，5ppm)，加药后12h，蚊幼的死亡率可达90～100％。
当烧杯水内异硫氰酸丙烯酯终浓度为0.00025％(w/w，2.5ppm)，加药后12h，蚊幼的死亡率达40～70％。但是，该实验重现性不好。
对照药剂，在25mL去氯离子水的烧杯中加入1g 1％双硫磷颗粒，放入30头活力健壮、大小一致的3龄幼蚊，加药后12h，白纹伊蚊和库蚊的死亡率均可达99～100％。
空白对照，在25mL去氯离子水的烧杯中直接放入30头活力健壮、大小一致的3龄白纹伊蚊和库蚊，不加药，观察1～24h，蚊幼的死亡率为0。
2.现场药效的测定
2.1试验方法
采用国家GB/T 31711-2015《卫生杀虫剂现场药效测定与评价杀蚊幼剂》标准。
2.2试验用蚊虫
来自山西巴盾环境保护技术研究所提供的野外培育池，每个池的面积1m 2，水深20cm，池内有足量的2～3龄伊蚊和库蚊。
2.3用药量
按1.0g/m 2用药量计。
2.4试验结果
每平方米用0.005％浓度(w/w，50ppm)的异硫氰酸丙烯酯乳液1g，喷撒于水面，药后12h，蚊幼的死亡率达90％，24h后达100％。
对照药剂采用1％双硫磷颗粒(德国安倍产)，每平方米用药1g，人工撒布，沉于水底，12h后蚊幼的死亡率为80％，24h后达99％。
空白对照，无加药，24h后蚊幼死亡率为0。
二、小结
1、室内药效
(1)浓度为5ppm、25ppm、50ppm的异硫氰酸丙烯酯乳液，作用12h，对蚊 幼的致死率达到80～100％；
(2)浓度为2.5ppm的异硫氰酸丙烯酯乳液，作用12h，对蚊幼的致死率40～70％，该实验重现性不好，有待进一步研究。
2、现场药效
(1)0.005％浓度(50ppm)的异硫氰酸丙烯酯对库蚊、伊蚊等蚊幼具有可靠、快速的灭杀作用，而且，载体和乳化剂的变化对异硫氰酸丙烯酯的药效没有影响。
(2)0.005％浓度(50ppm)的异硫氰酸丙烯酯乳液与1％双硫磷颗粒剂比较，灭蚊幼的作用无明显差异。
按照上述相同的方法，本发明测定了实施例3-7以及其他没有列举的实施例的室内以及现场药效，大量的实验研究和试验证明，只要保证异硫氰酸丙烯酯的使用浓度在5～50ppm范围内，在本发明所述的范围内适当调整配方和配比，特别是调整或替换不同的乳化剂或载体，不会影响本发明的灭蚊幼效果以及最终目的。
本发明实施例具体而详实地描述了全部技术，因此，有助于本领域技术人员或非专业人员理解本发明。本发明无论对于本领域的技术人员，或非本领域的人员，均可在不脱离本发明、发现、应用的前提下，轻松地制备出类似本发明的异硫氰酸丙烯酯灭蚊幼制剂，并还可以做出若干变形或改进型产品，包括固体、粉体、微胶囊、悬浮剂等不同剂型的产品，这些变形或改进均属于本发明的保护范围。

Claims (10)

  1. 异硫氰酸丙烯酯在制备灭蚊幼制剂中的用途。
  2. 如权利要求1所述的用途，其特征在于，所述的异硫氰酸丙烯酯的有效工作浓度为5～50ppm。
  3. 一种食品级灭蚊幼制剂，其特征在于，含有异硫氰酸丙烯酯作为灭蚊幼的有效成分。
  4. 如权利要求3所述的灭蚊幼制剂，其特征在于，所述的灭蚊幼制剂由以下重量百分比的各原料组成：
    异硫氰酸丙烯酯    1～40％
    乳化剂            2～40％
    载体              20～97％。
  5. 如权利要求4所述的灭蚊幼制剂，其特征在于，所述的乳化剂为AS02-30月桂酰肌氨酸钠、单十二烷基磷酸酯钾、烷基酚聚氧乙烯醚(OP-10)、异辛醇聚氧乙烯醚磷酸酯、壬基酚聚氧乙烯醚、壬基酚聚氧乙烯醚磷酸酯、聚氧乙烯醚、十二烷基硫酸钠、十二烷基苯磺酸钙、茶皂素、木质素磺酸钠、木质素磺酸钙、十二烷基苯磺酸钠、醇醚羧酸盐AEC-9、植物型聚氧乙烯醚、吐温80、乙二醇酯、丙二醇酯以及聚乙二醇的一种或几种的混合，优选的，所述的乳化剂为AS02-30月桂酰肌氨酸钠、烷基酚聚氧乙烯醚(OP-10)、茶皂素、聚乙二醇或NSF-10E聚氧乙烯醚，更优选为AS02-30月桂酰肌氨酸钠；所述载体为微孔淀粉或微硅粉，优选的，所述的微硅粉的粒径为400～800目。
  6. 如权利要求5所述的灭蚊幼制剂，其特征在于，所述的植物型聚氧乙烯醚包括NSF-10E聚氧乙烯醚、NSF-7聚氧乙烯醚、NSF-9聚氧乙烯醚、NSF-10聚氧乙烯醚以及NSF-20聚氧乙烯醚。
  7. 如权利要求4所述的灭蚊幼制剂，其特征在于，所述的灭蚊幼制剂为粉剂或乳液。
  8. 一种制备权利要求3-7任一项所述的灭蚊幼制剂的方法，其特征在于，包括以下步骤：
    当所述的灭蚊幼制剂为乳液时：
    (1)按照以下重量百分比分别称取各原料，备用；
    异硫氰酸丙烯酯    1～40％
    乳化剂            2～40％
    载体              20～97％
    (2)将称取的异硫氰酸丙烯酯、乳化剂、载体混合，通过液体泵泵入高压均质机内，选择合适的工作压力以及进料压力，均质，即可制得含有异硫氰酸丙烯酯的灭蚊幼乳液；
    其中，优选的高压均质机的工作压力为60～200MPa，更优选的工作压力为80～120MPa，进料压力为0.1～2MPa，优选0.8MPa，均质时间为10～50min；
    当所述的灭蚊幼制剂为粉剂时：
    (1)按照以下重量百分比分别称取各原料，备用；
    异硫氰酸丙烯酯    1～40％
    乳化剂            2～40％
    载体              20～97％
    (2)将异硫氰酸丙烯酯和乳化剂混合；
    (3)将载体放入普通粉碎机内，开机；
    (4)在搅拌的状态下，将异硫氰酸丙烯酯和乳化剂的液体混合物，缓慢加入到装有载体的粉碎机内，使异硫氰酸丙烯酯和乳化剂与载体均匀接触、吸附，加注完液体混合物后，粉碎机继续工作20～40min，然后停机，出料，真空包装，即可制得异硫氰酸丙烯酯灭蚊幼粉剂。
  9. 权利要求3-7任一项所述的灭蚊幼制剂在治理蚊幼中的用途，其中，优选的，所述的蚊幼包括伊蚊属(Aedes)、库蚊属(Culex)、埃及伊蚊(Aedes aegypti)、按蚊属(Anopheles)、环须按蚊(Anophelesannulipes)、阿蚊属(Armigeres)、艾蚊属(Ayurakitia)、伯罗按蚊属(Bironella)、鲍蚊属(Borichinda)、恰氏蚊属(Chagasia)、轲蚊属(Coquillettidia)、致倦库蚊(Culex quinquefasciarus)、环纹库蚊(Culex annulirostris)、脉毛蚊属(Culiseta)、费蚊属(Ficalbia)、趋血蚊属(Haemagogus)、领蚊属(Heizmannia)、霍蚊属(Hodgesia)、金蚊属(Kimia)、钩蚊属(Malaya)、曼蚊属(Mansonia)、小蚊属(Mimomyia)、直脚蚊属(Orthopodomyia)、鳞蚊属、煞蚊属(Sabethes)、土蚊属(Topomyia)、巨蚊属(Toxorhynchites)、前毛蚊属(Trichoprosopon)、杵蚊属(Tripteroides)以及尤蚊属(Udaya)蚊幼。
  10. 如权利要求9所述的用途，其特征在于，将所述的灭蚊幼制剂稀释至异硫氰酸丙烯酯的工作浓度为5～50ppm使用。
PCT/CN2019/000127 2018-07-06 2019-06-17 一种食品级灭蚊幼制剂及其制备方法和应用 WO2020007018A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201810739257.7A CN108684699A (zh) 2018-07-06 2018-07-06 一种食品级灭蚊幼制剂及其制备方法和应用
CN201810739257.7 2018-07-06

Publications (1)

Publication Number Publication Date
WO2020007018A1 true WO2020007018A1 (zh) 2020-01-09

Family

ID=63851448

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2019/000127 WO2020007018A1 (zh) 2018-07-06 2019-06-17 一种食品级灭蚊幼制剂及其制备方法和应用

Country Status (2)

Country Link
CN (1) CN108684699A (zh)
WO (1) WO2020007018A1 (zh)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108684699A (zh) * 2018-07-06 2018-10-23 王渊 一种食品级灭蚊幼制剂及其制备方法和应用
CN114467929A (zh) * 2022-02-24 2022-05-13 山西巴盾环境保护技术研究所 一种可长期悬浮在水面并可回收的灭蚊幼材料其制备方法与应用

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1236553A (zh) * 1999-06-01 1999-12-01 童忠良 新型天然植物驱蚊膏
CN1709957A (zh) * 2005-06-17 2005-12-21 华南农业大学 驱蝇塑料瓶盖的制法及其在调味品包装品中的应用
CN101186772A (zh) * 2007-12-04 2008-05-28 华南农业大学 驱蝇蚊乳胶漆及其制备方法
JP2012180297A (ja) * 2011-02-28 2012-09-20 Kohendo:Kk ボウフラ駆除組成物
US20150313219A1 (en) * 2010-04-09 2015-11-05 Pacific Tech Industries, Inc. Grease-like gel for repelling insects and preventing undesirable behavior in hoofed animals
CN107027826A (zh) * 2017-04-25 2017-08-11 黄山力神日用品有限公司 一种植物源驱蚊剂
US20170347666A1 (en) * 2010-12-20 2017-12-07 Mpt Mustard Products & Technologies Inc. Mixtures of Mustard Plant Material For The Control of Pests and Methods of Making
CN108684699A (zh) * 2018-07-06 2018-10-23 王渊 一种食品级灭蚊幼制剂及其制备方法和应用

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103719166A (zh) * 2013-12-12 2014-04-16 江苏集贤绿色化学科技研究院有限公司 一种复合熏蒸杀虫剂及其制备方法

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1236553A (zh) * 1999-06-01 1999-12-01 童忠良 新型天然植物驱蚊膏
CN1709957A (zh) * 2005-06-17 2005-12-21 华南农业大学 驱蝇塑料瓶盖的制法及其在调味品包装品中的应用
CN101186772A (zh) * 2007-12-04 2008-05-28 华南农业大学 驱蝇蚊乳胶漆及其制备方法
US20150313219A1 (en) * 2010-04-09 2015-11-05 Pacific Tech Industries, Inc. Grease-like gel for repelling insects and preventing undesirable behavior in hoofed animals
US20170347666A1 (en) * 2010-12-20 2017-12-07 Mpt Mustard Products & Technologies Inc. Mixtures of Mustard Plant Material For The Control of Pests and Methods of Making
JP2012180297A (ja) * 2011-02-28 2012-09-20 Kohendo:Kk ボウフラ駆除組成物
CN107027826A (zh) * 2017-04-25 2017-08-11 黄山力神日用品有限公司 一种植物源驱蚊剂
CN108684699A (zh) * 2018-07-06 2018-10-23 王渊 一种食品级灭蚊幼制剂及其制备方法和应用

Also Published As

Publication number Publication date
CN108684699A (zh) 2018-10-23

Similar Documents

Publication Publication Date Title
US8187618B2 (en) Sustained release microbial insect control composition and means
CN112568235B (zh) 一种用于杀灭登革热等蚊媒传染病传播媒介蚊子的展膜油剂卫生杀虫剂及其制备方法
WO2020007018A1 (zh) 一种食品级灭蚊幼制剂及其制备方法和应用
CN105724389A (zh) 一种含氯虫苯甲酰胺的可分散油悬浮剂
CN103651550A (zh) 丁硫克百威和毒死蜱和阿维菌素复配微胶囊悬浮剂
CN104522054A (zh) 一种生物源增效复配杀虫剂、制备方法及其应用
CN100531572C (zh) 一种含天然除虫菊素和吡虫啉的农药组合物及其应用
CN106689186A (zh) 含有联苯菊酯和吡丙醚的高效杀虫组合物
CN109221191A (zh) 含有双丙环虫酯与吡蚜酮的杀虫组合物及其应用
CN102246778A (zh) 一种增效的杀虫组合物及其应用
CN109769842A (zh) 一种含有三氟苯嘧啶、鱼藤酮类化合物的杀虫剂组合物
CN101455204A (zh) 苯甲酰基脲类杀虫剂与噻嗪酮复配制剂
CN103931649B (zh) 甲氨基阿维菌素苯甲酸盐和氯烯炔菊酯的杀虫组合物
CN102246800A (zh) 一种含有茚虫威和呋虫胺的杀虫组合物
CN106035364A (zh) 一种含有七氟菊酯和灭蝇胺的杀虫组合物
CN107751219A (zh) 具有增效作用的杀虫剂组合物
CN102057942B (zh) 甲氨基阿维菌素苯甲酸盐噻嗯菊酯复配杀虫剂
CN105494450B (zh) 一种稳定性强的可降解天然除虫菊素乳液及其制备方法
CN104522041A (zh) 一种含有氟啶虫酰胺与高效氯氟氰菊酯的杀虫组合物
CN105123710B (zh) 一种含氟螨嗪的农药组合物及其制备方法
CN109392934A (zh) 一种含有乙唑螨腈与丁醚脲的杀虫组合物
CN111374148A (zh) 一种含烯虫酯的杀虫组合物
CN107691467A (zh) 一种甲维盐和高效氯氰菊酯复配的杀虫农药组合物及其制剂
CN109392937A (zh) 一种含有氟氯虫双酰胺与双三氟虫脲的杀虫组合物
CN103109846B (zh) 一种敌敌畏噻嗯菊酯复配杀虫剂

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19829815

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19829815

Country of ref document: EP

Kind code of ref document: A1