Flubendiamide was discovered by Japan pesticide Co., Ltd. in 1998 and developed jointly with Bayer since 2001. It is a kind of phthalamide compound. Like chlorfenoxamide, fluorofenoxamide also acts on the fish nicotine receptor of insects. Its birth was once the focus of attention and expectation, but it suffered twists and turns in 2016, and its subsequent market also attracted much attention.
Physical and chemical properties
Flufenoxamide technical is pure white crystal powder; Melting point: 217.5 ~ 220.7 ℃; Vapor pressure (25 ℃) < 1 × 10-1mPa; The solubility in water is 29.9 μ g/L(20℃); No explosion hazard, no spontaneous combustion, no oxidation.
Flufenoxamide has low toxicity and low risk to bees; Low toxicity and low risk to birds; Low risk and toxicity to fish; But it is highly toxic to silkworm and high risk; It is highly toxic to Daphnia magna and is forbidden to be used in rice fields.
Fluorobenzamide is a phthalamide compound, which has a unique mechanism of action. Like chlorfenoxamide, fluorofenoxamide is also a fish nicotine receptor agent. By stimulating the precipitation of calcium ions in insects, fluorobenzamide weakens muscle function, affects insect behavior and makes pests stop feeding quickly.
Fish nicotine receptors exist not only in insects, but also in mammals, but there are great differences in their structures, resulting in the high selectivity of flufenoxamide between insects and mammals and low toxicity to mammals. In addition, fluorobenzamide has very high activity to the 3rd instar larvae of Plutella xylostella, which is not possessed by carbamates, benzoylureas, pyrethroids and organophosphorus insecticides. Therefore, it is very suitable for resistance management and comprehensive management of pests.
Flufenoxamide has stomach toxicity and contact killing effect. It has no internal absorption, high efficiency and broad spectrum. It is suitable for many annual and perennial crops. Its main application crops include: soybeans, vegetables, fruit trees, corn, cotton, gourds, grapes, nut trees, rice, tobacco and tea trees. Fluorobenzamide has good activity against almost all lepidopteran pests. It can effectively control the adults and larvae of lepidopteran pests, especially the larvae, with fast action speed and long duration. Mainly through foliar spray.
European Patent: Compound patent (Japanese pesticide Co., Ltd.; phthalamide derivatives, or salt thereof, agrohorticultural pesticide, and method for using the same; phthalamide derivatives or their salts, pesticides for agriculture and horticulture and their use methods), ep1006107 was applied on November 24, 1999, and the patent expired on November 23, 2019. As of June 2017, the European patent has not applied for SPC (supplementary protection certificate) protection.
U.S. Patent: Compound patent (Japan pesticide Co., Ltd.; phthalamide derivatives, or salt thereof, agrohorticultural pesticide, and method for using the same; phthalamide derivatives or their salts, pesticides for agriculture and horticulture and their use methods), us6603044 applied for patent on November 29, 1999, and the patent expired on November 29, 2019.
Chinese patent: Compound patent (Japanese pesticide Co., Ltd.; phthalamide derivative or its salt, pesticide for agriculture and horticulture and its application method), cn1328246c, applied on November 30, 1999, and the patent expires on November 29, 2019.
At present, the compound patents of flufenoxamide in Europe, the United States and China have expired. Manufacturers with domestic demand can plan their registration.
Since its first registration in 2007, flufenoxamide has been registered in many countries around the world, such as Argentina, Australia, Bangladesh, Benin, Brazil, Cameroon, China, Chile, Colombia, Cyprus, Ghana, Greece, India, Ivory Coast, Japan, Liberia, Malaysia, Mexico, Morocco, the Netherlands, Nigeria, Pakistan, the Philippines, South Africa, South Korea, Spain China Taiwan, Thailand and Togo.
In 2006, the European Commission received Bayer's application for registration of flufenoxamide; That year, it was announced that the registration data were completed, and Greece was the drafting country of its document. In 2011, the provisional registration of flufenoxamide in the EU was extended until 31 July 2013. In 2013, the provisional registration was extended to April 30, 2015. In 2014, the European Commission approved the formal registration of flufenoxamide; On September 1, 2014, flufenoxamide was listed as a new active ingredient in the list of registered active ingredients in the EU pesticide registration regulation (1107 / 2009), which is valid until August 31, 2024.
In 2007, Japan pesticide Co., Ltd. registered and listed fluorobenzamide in Japan, with the trade name Phoenix, which is used for tea, vegetables, fruit trees and cotton to control Lepidoptera pests. In the same year, flufenoxamide was also registered in India, Pakistan, Chile, Brazil and the Philippines.
In 2008, the US EPA registered Bayer's flufenoxamide; In the same year, it was registered in South Korea; Temporary registration was obtained in China, and 96% flufenamide technical drug was officially registered on March 24, 2011.
In 2009, Bayer registered and marketed flufenoxamide in Australia and Mexico.
In 2011, Bayer launched the fluorobenzamide product belt in Argentina, which is used in soybeans, tomatoes, cotton and tobacco.
In 2013, Bayer listed tihan 175 o-teq (fluorobenzamide + spirochete ethyl ester) in Benin, Cameroon, Ghana, Ivory Coast, Liberia, Nigeria and Togo for cotton.
In 2014, Ivory Coast approved the registration of Bayer's compound insecticide belt expert 480 SC (fluorobenzamide + thiamethoxaline) for the control of Lepidoptera pests and stinging mouthparts pests.
In 2016, India's insecticides India reached an agreement with Japan pesticide Co., Ltd. to market Suzuka, a fluorobenzamide product of Japanese pesticide, in India.
The registered dosage forms mainly include: suspension, microemulsion, water dispersible granule, wettable powder, ultra-low volume liquid, suspension emulsion and emulsion, etc; It is mainly compounded with spirochete ethyl ester, avermectin, methylaminoavermectin benzoate, insecticide, thiazide, chlorpyrifos, thiazoline, hexazolol, pyraphid, profenofos, etc.
In 2001, Japanese pesticide and Bayer cooperated to jointly promote the market of flufenoxamide. In 2007, Bayer first launched the fluorobenzamide product belt. At present, fluorfenacicam has been sold in many countries, including Argentina, Australia, Bangladesh, Benin, Brazil, Cameroon, China, Chile, Columbia, Cyprus, Garner, Greece, India, Ivory Coast, Japan, Liberia, Malaysia, Mexico, Morocco, Morocco, Morocco, Holland, China, South Africa, South Korea, Spain, China, Thailand and Togo. The US market was interrupted due to environmental risks, while China banned the use of rice.
Flufenoxamide was listed in 2007; In 2011, the global sales reached 150 million US dollars; In 2012, the sales of flufenoxamide rose to US $230 million; In 2013, the global sales of flufenoxamide increased by 93.5% year-on-year to US $445 million; In 2014, global sales increased to $530 million (due to the cotton bollworm outbreak in Brazil), reaching a historical peak; In 2015, the global sales of flufenoxamide decreased by 9.4% year-on-year to USD 480 million; In 2016, the global sales of flufenoxamide was US $440 million.
Latin America is the main market for fipronamide, followed by Asia. In 2015, the sales volume of flufenoxamide in Latin America was US $245 million, accounting for 51.1% of the total market; Its sales in Asia were US $111 million, accounting for 23.2% of the total market.
Brazil is the largest national market of flufenoxamide, followed by India, China, the United States and Japan. In 2015, the sales volume of flufenoxamide in Brazil was US $228 million, accounting for 47.7% of the global market; The sales volume in India is 39 million US dollars, accounting for 8.2% of the global market; China and the United States ranked third and fourth, accounting for 5.3% and 4.1% respectively.
Soybean is the largest drug crop of flufenoxamide. In 2015, the sales of soybean, cotton, corn and rice were US $201 million, US $44 million, US $23 million and US $12 million respectively, and their market shares were 41.8%, 9.1%, 4.7% and 2.5% respectively. Other / non crops also accounted for a large weight of flufenoxamide. In 2015, the sales of flufenoxamide in this field was US $132 million, accounting for 27.5% of the global market.
Such a hot fluorobenzamide suffered a sudden setback in 2016. The United States Environmental Protection Agency (EPA) revoked its registration on more than 200 crops, China revoked its registration on rice, and China banned the use of fluorobenzamide on rice crops from October 1, 2018. Why does such a high-profile product suddenly encounter such a great "pressure"?
First, flufenoxamide can be decomposed into more toxic metabolites, causing harm to aquatic organisms and threatening the aquatic food chain (especially fish). It is highly toxic to Daphnia magna and algae, and the metabolite is persistent in the environment.
Secondly, flufenoxamide is very easy to make the target pests resistant. Single drug use faces a greater risk of pest resistance, and there is a risk of cross resistance between flufenoxamide and flufenoxamide due to the same effect on the fish nicotine receptor of insects.
Finally, for China, rice is a traditional crop in China. A large number of products have been registered for pest control of rice. There are 760 products for the control of rice stem borer and 900 products for the control of rice leaf roller. In the context of such registration, both chlorfenoxamide and neonicotine insecticides can perfectly replace fluorofenoxamide.
Although the United States prohibits the use of fipronamide and China prohibits its use in rice, its action mechanism is unique. In addition, the largest market of fipronamide is in Brazil and the largest applied crop is soybean, so this twists and turns has little impact on its market. In such a depressed environment, the sales of diamide insecticides are still growing. The author believes that fluorobenzamide will have a certain market share.