CN114208836A - Bactericidal composition containing ketoconazole and application thereof - Google Patents

Bactericidal composition containing ketoconazole and application thereof Download PDF

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CN114208836A
CN114208836A CN202111639316.1A CN202111639316A CN114208836A CN 114208836 A CN114208836 A CN 114208836A CN 202111639316 A CN202111639316 A CN 202111639316A CN 114208836 A CN114208836 A CN 114208836A
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ketoconazole
azoxystrobin
composition
bactericidal composition
germicidal
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CN114208836B (en
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陈昶
马超
徐军
张刚应
赵宜君
纪林东
段小莉
杨洋
张力卜
孙国强
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Hebei Zhongbao Lvnong Crops Technology Co ltd
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    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/601,4-Diazines; Hydrogenated 1,4-diazines
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N43/00Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/541,3-Diazines; Hydrogenated 1,3-diazines
    • YGENERAL 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
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
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  • Engineering & Computer Science (AREA)
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  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

The invention belongs to the field of pesticide bactericides, and particularly relates to a bactericidal composition which comprises a methoxy acrylate bactericide and ketoconazole, wherein the methoxy acrylate bactericide is azoxystrobin or pyraclostrobin; the mass ratio of the strobilurin fungicide to the ketoconazole is 10:1-1: 10; the bactericidal composition has obvious synergistic effect and excellent control effect on apple ring spot and strawberry anthracnose.

Description

Bactericidal composition containing ketoconazole and application thereof
Technical Field
The invention belongs to the field of pesticide bactericides and particularly relates to a bactericidal composition and application thereof.
Background
Apple ring rot is common and is one of the fungal diseases with serious harm to apple trees. The disease is mainly harmful to fruits and branches, the disease starts from the near-mature period of the apples to cause fruit rot, the disease fruit rate can reach 30% when the disease fruit is serious, and the disease can still occur in the storage period of the apples if the disease fruit rate is not well controlled in the growth period; 2 disease symptoms can be formed by infecting the branches, when the branches grow normally, ring rot symptoms are caused, and when the branches are stressed by water, dry rot symptoms are formed, so that the tree vigor is seriously weakened. Because of long-term continuous use of single medicament and blind mixed use of pesticides, the method causes a series of adverse effects of increased cost of pesticide application, high pesticide residue in fruits, development of resistance and the like.
Strawberry anthracnose caused by anthrax is an important disease in seedling stage and transplanting stage of strawberries, and mainly damages stolons and root crowns to cause rot of the root crowns, and finally causes plant wilting and death. At present, chemical control is mainly used for controlling strawberry anthracnose, and chemical agents such as difenoconazole and pyraclostrobin are mostly adopted for controlling strawberry anthracnose. Although the chemical agent can achieve good control effect in a short period of time, the chemical agent can cause the problems of fruit pesticide residue, environmental pollution, drug resistance of germs and the like.
Ketoconazole is an imidazole antifungal drug, and has an action mechanism of inhibiting the biosynthesis of ergosterol on fungal cell membranes, influencing the permeability of the cell membranes and inhibiting the growth of the cell membranes. Can be used for treating superficial and deep mycoses, such as skin and nail tinea, vaginal candidiasis, gastrointestinal fungal infections, etc., and systemic infections caused by Candida albicans, coccidioidomycosis, histoplasma bacteria, etc. In the prior art, the application research of ketoconazole in agricultural disease control is less. CN108684734A discloses a compound preparation for inhibiting the growth of cotton mold, which is a compound preparation obtained by compounding Chinese herbal medicine alcohol extract and ketoconazole; the Chinese herbal medicine alcohol extract is clove alcohol extract, phellodendron alcohol extract, salvia miltiorrhiza alcohol extract and coptis chinensis alcohol extract. CN101775357A discloses that ketoconazole has a strong inhibitory effect on plant pathogenic fungi fusarium moniliforme.
Azoxystrobin is a methoxy acrylate bactericide developed by Syngenta, and is a bactericide which acts on mitochondrial respiration through inhibiting mitochondrial respiration, but the action part of a methoxy acrylate compound is different from that of all conventional bactericides, so that the azoxystrobin is effective in preventing and treating strains which generate resistance to sterol inhibitors, phenylamides, dicarboxamides and benzimidazoles. Has protective, therapeutic, relieving, penetrating, and systemic activities. Has good activity on almost all fungal diseases (ascomycetes, basidiomycetes, oomycetes and fungi imperfecti) such as powdery mildew, rust disease, glume blight, net blotch, scab, downy mildew, rice blast and other dozens of diseases.
Pyraclostrobin, also known as pyraclostrobin, can prevent and treat plant diseases caused by almost all types of fungal pathogens such as ascomycetes, basidiomycetes, deuteromycetes and oomycetes, and is a hormone-type bactericide which can enable crops to absorb more nitrogen and promote the growth of the crops. The product has low toxicity, is safe to non-target organisms, does not pollute users and the environment, and can be compounded and mixed with various bactericides to play roles in enhancing the effect and expanding the bactericidal spectrum.
In the prior art, no report is provided about the application of ketoconazole in preventing and treating apple ring rot and strawberry anthracnose, and no report is provided about the application of ketoconazole in preventing and treating apple ring rot and strawberry anthracnose after the strobilurin fungicide and ketoconazole are compounded.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: provides a sterilization composition with synergistic effect, slows down the generation of drug resistance of germs and reduces the dosage of pesticides. The invention provides the following technical scheme:
a sterilization composition comprises a methoxy acrylate bactericide and ketoconazole, wherein the methoxy acrylate bactericide is azoxystrobin or pyraclostrobin, and the mass ratio of the methoxy acrylate bactericide to the ketoconazole is 10:1-1: 10. The preferred mass ratio of the strobilurin fungicide to the ketoconazole is 9:1-7:3 and 1: 9; the more preferable mass ratio of the strobilurin fungicide to the ketoconazole is 1: 9.
The total mass percentage of the strobilurin fungicide and the ketoconazole in the sterilization composition is 5% -75%. The total mass percentage of the optimized strobilurin fungicide and ketoconazole in the fungicide composition is 10-50%
The bactericidal composition also contains auxiliary components of pesticide preparations so as to prepare the bactericidal composition into a dosage form suitable for agriculture. The auxiliary components are selected from one or more of solvent, emulsifier, dispersant, wetting agent, antifreeze agent, preservative, synergist, binder, thickener, disintegrant, defoamer and carrier.
The dosage form of the bactericidal composition is wettable powder, missible oil, suspending agent, aqueous emulsion, microemulsion or water dispersible granules. The selected dosage forms of the bactericidal composition are wettable powder, water dispersible granules and suspending agents
The bactericidal composition is applied to the prevention and control of crop diseases. The selected diseases are apple ring spot and strawberry anthracnose.
Compared with the prior art, the invention has the beneficial effects that:
1. when the azoxystrobin and the ketoconazole are compounded, the mass ratio of the azoxystrobin to the ketoconazole is 9:1, 7:3 and 1:9, so that the azoxystrobin and the ketoconazole have obvious synergistic effect on ring rot of apple; when the mass ratio of the azoxystrobin to the ketoconazole is 1:9, the synergistic effect on strawberry anthracnose pathogen is obvious.
2. When the 10% azoxystrobin and ketoconazole wettable powder, the 20% azoxystrobin and ketoconazole water dispersible granule and the 10% azoxystrobin and ketoconazole suspending agent are diluted by 1000-fold and 2000-fold, the apple ring rot control agent has excellent control effect, and the control effect is about 90%;
3. the ketoconazole can be used for preventing and treating ring rot of apples and anthracnose of strawberries by singly using the ketoconazole;
4. after the azoxystrobin and the ketoconazole are compounded, the use dosage of active ingredients can be effectively reduced, and the generation of drug resistance of germs can be slowed down.
Detailed Description
Through the toxicity screening of the azoxystrobin and the ketoconazole on fungal plant pathogenic bacteria, the apple ring spot and the strawberry anthracnose which are sensitive to single-dose toxicity are selected to carry out the compound toxicity synergy test, and the test result is as follows.
Example 1: determination of combined action of azoxystrobin and ketoconazole composition on physalospora piricola
1.1 materials
Test strains: collecting apple ring rot germ (Botryosphaeridothidea) in field, separating, purifying and identifying by tissue separation method, and storing in refrigerator at 4 deg.C for use.
Reagent to be tested: azoxystrobin and ketoconazole; is commercially available
1.2 test methods: the toxicity of single and mixed agents is determined by a hypha growth rate method. 6 concentration gradients are set for single dose of azoxystrobin and single dose of ketoconazole. The azoxystrobin and the ketoconazole are mixed according to 5 effective component ratios of 9:1, 7:3, 1:1, 3:7 and 1:9, and each ratio is provided with 6 concentration gradients. The PDA medium containing the drug was poured into a petri dish with a diameter of 9cm and 3 replicates of each concentration were set using PDA plates without drug as blank. Inoculating the ring rot germ activated bacterium cake with the diameter of 5mm into the center of the plate, and culturing in a constant temperature incubator at 26 ℃. After 5 days of culture, the growth diameter of the hypha mass was measured by the cross method.
Calculating a regression equation (y is A + Bx), a correlation coefficient (r), EC50 and a synergy coefficient (SR) of the toxicity of the single dose of azoxystrobin, the ketoconazole and each mixed dose to the ring rot apple. The toxicity of different mixed combinations is judged according to the synergistic coefficient (SR), wherein the antagonism is obtained when the SR is less than 0.5, the addition is obtained when the SR is between 0.5 and 1.5, and the synergism is obtained when the SR is more than 1.5.
1.3 results and analysis
The test respectively detects the indoor toxicity of the compound agents with different proportions of azoxystrobin and ketoconazole on the ring spot of apple ring spot, and the detection and evaluation results are shown in table 1.The results show that: the single-dose toxicity effect of the azoxystrobin and the ketoconazole on the ring rot apple germs is obvious, and EC500.2746 μ g/ml and 0.0983 μ g/ml, respectively. In the compound proportion, the azoxystrobin, ketoconazole and ketoconazole have the toxicity synergy coefficient SR more than 1.5 in the proportion of 9:1, 7:3 and 1:9, and have the synergy; the effect was additive at a ratio of 1:1 and antagonistic at 3: 7. The ratio of 9:1 to 1:9 of the three synergistic ratios is higher in synergistic coefficient, which indicates that the smaller the proportion of one single agent is, the more obvious the synergistic effect is.
TABLE 1 measurement of the Combined Effect of azoxystrobin and Ketoconazole on Physalospora Mali
Figure BDA0003442280180000041
Figure BDA0003442280180000051
Example 2: determination of combined action of azoxystrobin and ketoconazole on strawberry colletotrichum gloeosporioides
2.1 materials
Test strains: strawberry anthrax (Colletotrichumgloeosporioides) collected in greenhouse, separated, purified and identified by tissue isolation method for use.
Reagent to be tested: azoxystrobin and ketoconazole; is commercially available
2.2 test methods: the toxicity of single and mixed agents is determined by a hypha growth rate method. 6 concentration gradients are set for single dose of azoxystrobin and single dose of ketoconazole. The azoxystrobin and the ketoconazole are mixed according to 5 effective component ratios of 9:1, 7:3, 1:1, 3:7 and 1:9, and each ratio is provided with 6 concentration gradients. The PDA medium containing the drug was poured into a petri dish with a diameter of 9cm and 3 replicates of each concentration were set using PDA plates without drug as blank. Inoculating the ring rot germ activated bacterium cake with the diameter of 5mm into the center of the plate, and culturing in a constant temperature incubator at 28 ℃. When the control colony grows over the petri dish 2/3, the growth diameter of the mycelium pellet was measured by the cross method.
Calculating the regression equation (y is A + Bx), the correlation coefficient (r), the EC50 and the synergy coefficient (SR) of the toxicity of the single dose of azoxystrobin, the ketoconazole and each mixed dose to the strawberry anthracnose pathogen. The toxicity of different mixed combinations is judged according to the synergistic coefficient (SR), wherein the antagonism is obtained when the SR is less than 0.5, the addition is obtained when the SR is between 0.5 and 1.5, and the synergism is obtained when the SR is more than 1.5.
2.3 results and analysis
The test respectively detects the indoor toxicity of the compound agents with different proportions of azoxystrobin and ketoconazole on strawberry anthrax bacteria, and the detection and evaluation results are shown in table 2. The results show that: the single dose toxicity effect of the azoxystrobin on strawberry anthracnose pathogen is obvious, and EC500.0495. mu.g/ml, EC of ketoconazole on strawberry anthracnose pathogen504.6284. mu.g/ml. In the five compound proportions, only the azoxystrobin and the ketoconazole have synergistic action in a ratio of 1:9, and the synergistic coefficient SR is 5.4529, so that the synergistic effect is obvious; in other ratios, the azoxystrobin and ketoconazole are antagonistic at 7:3, and the others are additive. This shows that when the azoxystrobin accounts for a small proportion, the synergistic effect of the azoxystrobin and the azoxystrobin is obvious.
TABLE 2 measurement of the Combined Effect of azoxystrobin and Ketoconazole combinations on strawberry anthracnose
Figure BDA0003442280180000061
EXAMPLE 3 formulation
10% azoxystrobin ketoconazole wettable powder
Figure BDA0003442280180000062
Figure BDA0003442280180000071
The active ingredients, various additives, fillers and the like are fully mixed according to the proportion of the formula and crushed by an ultrafine crusher to obtain the 10 percent azoxystrobin ketoconazole wettable powder.
20% azoxystrobin ketoconazole water dispersible granule
Figure BDA0003442280180000072
The active component, dispersant, wetting agent, disintegrating agent, binder and filler are mixed uniformly according to the proportion of the formula, and are pulverized into wettable powder by air flow, and a certain amount of water is added for mixing and extrusion molding. Obtaining the 20 percent azoxystrobin ketoconazole water dispersible granule after drying and screening.
10% azoxystrobin-ketoconazole suspending agent
Figure BDA0003442280180000073
Figure BDA0003442280180000081
The active ingredients, the auxiliary materials and other components are uniformly mixed according to the proportion of the formula, and the 10 percent azoxystrobin ketoconazole suspension is obtained after grinding and high-speed shearing.
Example 4 field Effect test of azoxystrobin and Ketoconazole combinations on apple ring rot
Test materials: apple varieties to be tested: red Fuji; the control object is: ring rot of apple
Reagent to be tested: example 3 of the present invention
The test method comprises the following steps: reference is made to the pesticide field test guidelines GB/T17980.118-2004. 3 medicament treatments and 1 clear water blank control are set for the test, and the total number of the treatments is 4; each cell comprises 4 fruit trees with consistent growth vigor; repeat 4 times, random block permutation. The spraying device for the test is a knapsack electric sprayer; spraying the pesticide for 14 days after the apple flowers fall for the first time, and spraying the pesticide for 1 time every 15 days for 3 times in total; spraying the liquid medicine on each fruit tree uniformly and thoroughly, and dripping the liquid medicine slightly. When the apples are harvested, all fruits and fallen fruits on 2 apple trees in each district are investigated, and the total number of fruits and the number of diseased fruits are recorded.
The calculation formula is as follows:
disease fruit rate (%) (number of investigated disease fruits/total number of investigated fruits) × 100;
control effect (%) [ (blank control area fruit disease rate-treatment area fruit disease rate)/blank control area fruit disease rate ] × 100
Results and analysis: the test respectively detects the control effect of the azoxystrobin and the ketoconazole on the ring rot of apple, and the detection and evaluation results are shown in table 2. The results show that: when the 10% azoxystrobin and ketoconazole wettable powder, the 20% azoxystrobin and ketoconazole water dispersible granule and the 10% azoxystrobin and ketoconazole suspending agent are diluted by 1000-fold and 2000-fold, the apple ring rot control agent has excellent control effect, and the control effect is about 90%.
TABLE 3 field control of the azoxystrobin and ketoconazole combinations against ring rot of apple
Figure BDA0003442280180000082
Figure BDA0003442280180000091
The present invention will be described in detail with reference to examples. In the present invention, the following examples are intended to better illustrate the present invention and are not intended to limit the scope of the present invention. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

Claims (9)

1. A germicidal composition, characterized by: the bactericidal composition comprises a methoxy acrylate bactericide and ketoconazole, wherein the mass ratio of the azoxystrobin to the ketoconazole is 10:1-1: 10; the strobilurin fungicide is azoxystrobin or pyraclostrobin.
2. The germicidal composition of claim 1, wherein: the mass ratio of the strobilurin fungicide to the ketoconazole is 9:1-7:3 and 1: 9.
3. The germicidal composition of claim 1, wherein: the mass ratio of the strobilurin fungicide to the ketoconazole is 1: 9.
4. The germicidal composition as claimed in any one of claims 1 to 3, wherein: the total mass percentage of the strobilurin fungicide and the ketoconazole in the fungicide composition is 5-75%.
5. The germicidal composition of claim 4, wherein: the bactericidal composition also contains auxiliary components of pesticide preparations so as to prepare the bactericidal composition into a dosage form suitable for agriculture.
6. The germicidal composition of claim 5, wherein: the auxiliary components are one or more of solvent, emulsifier, dispersant, wetting agent, antifreeze agent, preservative, synergist, binder, thickener, disintegrant, defoamer and carrier.
7. The germicidal composition of claim 5, wherein: the dosage form of the bactericidal composition is wettable powder, missible oil, suspending agent, aqueous emulsion, microemulsion or water dispersible granules.
8. Use of the fungicidal composition according to any one of claims 1 to 7 for the control of crop diseases.
9. Use according to claim 8, characterized in that: the diseases are apple ring spot and strawberry anthracnose.
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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IN2013DE03504A (en) * 2013-12-03 2015-06-12 Crystal Crop Prot Pvt Ltd

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IN2013DE03504A (en) * 2013-12-03 2015-06-12 Crystal Crop Prot Pvt Ltd

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
李惠明 等: "《蔬菜病虫害诊断与防治实用手册》", 上海科学技术出版社 *

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