CN103535347A - Solid or liquid pesticide composition of cyclodextrin and dipyridyl herbicide clathrate compound, and preparation method of composition - Google Patents

Abstract

The invention discloses a solid or liquid pesticide composition of cyclodextrin and bipyridine herbicide clathrate, which comprises bipyridine herbicide and cyclodextrin with a mass ratio of 1:0.5-1:9. The invention also discloses a preparation method of a solid or liquid pesticide composition of cyclodextrin and bipyridyl herbicide clathrate, comprising the following steps: mixing 9 parts by mass of cyclodextrin with 9 to 63 parts by mass of water Mix, add 1-18 mass parts of bipyridyl herbicides, and mix thoroughly; heat at 60-80°C under dark conditions, stir to make the system completely uniform or dissolve, and then keep warm for 1 hour; prepare the system that completely dissolves into a solution A liquid pesticide composition is obtained; a powdery solid pesticide composition is obtained from a uniform or dissolved system. The pesticide composition of the present invention can be liquid or solid, and the bipyridyl herbicide clathrate has strong activity, stable properties, long shelf life, and lower irritation than ordinary water formulations, which reduces contact damage to humans and animals, and is not easy to spread and pollute the environment .

Description

Solid or liquid pesticide composition of inclusion compound of cyclodextrin and bipyridine herbicide and preparation method thereof

technical field

The invention relates to a new type of pesticide composition of bipyridine herbicides, in particular to a solid or liquid pesticide composition of cyclodextrin and bipyridine herbicide clathrates and a preparation method.

Background technique

The herbicides with bipyridine cationic structure widely used in agriculture and forestry mainly include paraquat and diquat. Paraquat (Paraquat), common trade name: Gramoxone (Gramoxone), chemical name: 1-1'-dimethyl-4-4'-bipyridine cationic salt, this product forms salts with different acid radicals, the common ones are Two products, dichloride and monomethyl disulfate, are: paraquat dichloride, molecular formula: C ₁₂ H ₁₄ C ₁₂ N ₂ , molecular weight: 257.2; paraquat monomethyl disulfate, molecular formula: C ₁₄ H ₂₀ N ₂ O ₈ S ₂ , molecular weight: 408.44. Paraquat dichloride is a colorless crystal with a melting point of 300°C (decomposition), and its monomethyl bissulfate salt is a yellow solid. Diquat, chemical name: 1,1'-ethylene-2,2'-bipyridyl dibromide, colorless to light yellow crystal, monohydrate light yellow solid, melting point 320°C (decomposition). Bipyridyl herbicides have a planar ring structure and exhibit strong UV absorption, with a high molar absorption coefficient ε (2.0×104 for paraquat; 1.8×104 for diquat).

Bipyridyl herbicides are all ionic compounds, easily soluble in water, slightly soluble in lower alcohols, hardly soluble in hydrocarbon organic solvents, compounds with good thermal stability, poor light stability, stable to acids, and stable to alkalis. Easy to decompose. Its aqueous solution is usually used. These products are non-selective herbicides with contact and systemic effects. It can be quickly absorbed by the green tissue of plants, causing them to die, and it is ineffective for plant roots, perennial underground stems and perennial roots. At present, the commonly used preparation product is 20% content water agent, the dosage per hectare is 300-900 grams (original drug), and the recommended concentration in Daejeon is 600 mg.L-1 (ppm)-1600 mg.L-1. After spraying, the drug can quickly combine with the soil and passivate. Therefore, in order to improve the effect of the drug, the actual application concentration is often above 2000ppm, and the product is used in excess, with low safety and large waste.

Bipyridyl herbicides are highly toxic to both humans and animals, with low lethal doses, can be partially absorbed through the skin, and can cause skin damage at high concentrations. The atomized soluble concentrate can be inhaled through the respiratory organs and cause poisoning, and accidental or deliberate ingestion of more than 30ml of 20% liquid can be fatal. The 20% paraquat water solution currently sold in the market is inconvenient to pack and carry, and has low safety in use. Existing products have a large amount of actual application and high concentration, which can easily cause human and animal poisoning. Therefore, reducing the dose to reduce toxicity hazards, reducing the possibility of misuse by changing the dosage form, making it easy to carry and transport, and improving its safety in use are the current focus of research on paraquat products.

The prior art works from the aspects of improving dosage forms, improving safety and enhancing effects. CN1247026A combines emesis, malodor, surfactant and adsorbent with paraquat to prepare a solid or semi-solid dosage form product. Due to the use of The poorly soluble adsorbent and the incomplete dissolution of the preparation affect the performance of the drug activity. CN1192708C prepares disperse granules by combining multiple components, and the killing effect on weeds is not significantly different from that of existing water-based products. In the technology disclosed in CN1618289A, hydrochloric acid and synergist are added to paraquat aqueous solution to make a combination of herbicides. Compared with the original product, there is no significant change in the use effect, and its high content of hydrochloric acid not only reduces product safety but also increases Chemical pollution after use. In the study aimed at enhancing the effect, by adding plant growth regulators gibberellin, naphthalene acetic acid and indole acetic acid (50mg. Paraquat (100mg.L-1) has also been observed to have a significant synergistic effect (Hubei Agricultural Sciences, 4, 2003: P54-56), but whether the synergistic effect brings about enhanced toxicity and increased residues, and whether the compound combination A series of uncertainties such as the stability of the final preparation still need to be further studied. The products currently used in the market are all 20% water formulations with different contents of surfactants added. It can be seen that the existing water preparation products have shortcomings such as easy ingestion, poor skin contact safety, high concentration and large dosage, difficult transportation and carrying, inconvenient use, and easy loss. Although many improved technologies have been proposed, there is still no A comprehensive solution to the paraquat problem could replace existing products.

In addition, at present, bipyridyl herbicides are applied at relatively high concentrations in practical applications, and the phenomenon of association of drug molecules is extremely significant, which will produce extremely adverse effects. The association of molecules produces larger association molecules, which will hinder the penetration of drugs into plant membranes, affect the diffusion of drugs, and reduce the efficacy of drugs. The association of a large number of molecules is more likely to lead to the inactivation of drug activity.

Cyclodextrin inclusion technology is often applied to drugs with poor solubility or low chemical stability to improve drug water solubility, enhance drug stability, improve bioavailability and remove drug odor. Since paraquat is a solid product with strong water solubility and relatively stable chemical properties, there are no relevant reports on the application of cyclodextrin in improving paraquat preparations and enhancing activity.

Contents of the invention

The object of the present invention is to provide a solid or liquid pesticide composition of cyclodextrin and bipyridyl herbicide clathrate with weak irritation and strong safety and its preparation method in order to solve the above problems.

The present invention achieves the above object through the following technical solutions:

The solid or liquid pesticide composition of cyclodextrin and bipyridine herbicide clathrate of the present invention comprises bipyridine herbicide and cyclodextrin in a mass ratio of 1:0.5-1:9.

Preferably, the mass ratio of the bipyridyl herbicide to cyclodextrin is 1:1-1:6; more preferably 1:4.5.

Specifically, the bipyridyl herbicide is paraquat dichloride, paraquat monomethyl sulfate or diquat dibromide; the cyclodextrin is a single cyclodextrin or multiple single cyclodextrins Composed of mixed cyclodextrins, wherein the single cyclodextrin is β-cyclodextrin, hydroxypropyl-β-cyclodextrin, hydroxyethyl-β-cyclodextrin, hydroxybutyl-β-cyclodextrin Glycol or sulfobutyl-β-cyclodextrin, the mixed cyclodextrin includes β-cyclodextrin with a mass percentage of 10-90%.

The bipyridyl herbicide is preferably paraquat dichloride.

Further, the solid or liquid pesticide composition also includes a surfactant with a mass percentage of 10% to 30%, and the surfactant is ionic and/or nonionic; the ionic surfactant is selected from: Sodium laureth succinate sulfonate, sodium dodecylbenzene sulfonate, sodium cetyl sulfonate, sodium dioctyl sulfosuccinate, and sodium dibutylnaphthalene sulfonate; the non- The ionic surfactant is selected from the group consisting of: polyoxyethylene-polyoxypropylene copolymer, isooctyl alcohol polyoxyethylene ether, lauryl alcohol polyoxyethylene ether, stearyl alcohol polyoxyethylene ether and Tewin-80.

Specifically, the surfactant is composed of one ionic surfactant mixed with 2 to 3 nonionic surfactants; the ionic surfactant and the nonionic surfactant The mass ratio of the agent is 2: (0-5).

In application, the solid or liquid pesticide composition is also added with pharmaceutical auxiliaries or auxiliary materials; wherein, the liquid pesticide composition is added with a buffer salt or electrolyte whose mass is 0-20% of the mass of the liquid pesticide composition, so The buffer salt is potassium dihydrogen phosphate, and the electrolyte is ammonium nitrate, potassium nitrate or calcium phosphate; hydroxypropyl cellulose, hydroxypropyl cellulose, Soluble starch, lactose, polyethylene glycol or mannitol, prepared as a solid preparation.

The preparation method of the solid or liquid pesticide composition of cyclodextrin and bipyridine herbicide clathrate of the present invention comprises the following steps:

(1) Mix 9 parts by mass of cyclodextrin with 9 to 63 parts by mass of water, add 1 to 18 parts by mass of bipyridyl herbicides, and mix thoroughly;

(2) Heat at 60-80°C under dark conditions, stir to make the system completely uniform or dissolve, and then keep warm for 1 hour;

(3) Cool the completely dissolved system obtained in step (2) to room temperature, filter, concentrate, measure the actual content of paraquat and then adjust it to the required concentration with water to obtain paraquat containing 10% to 25% by mass. A liquid pesticide composition of bipyridyl herbicides; the homogeneous or dissolved system obtained in step (2) is evaporated to remove water at 60°C, and then dried under reduced pressure at 50°C to obtain a solid, which is crushed to obtain a mass percentage The powdery solid pesticide composition is 10%-30% bipyridyl herbicide.

The following methods are preferred:

The preparation method of the liquid pesticide composition is as follows: mix 1 mass part of highly water-soluble cyclodextrin with 2 mass parts of water, add 1 mass part of bipyridyl herbicide, mix well, and heat to Stir at 60°C to dissolve the system, and then keep it warm for 1 hour; cool the solution to room temperature, filter, concentrate, measure the actual content of paraquat, and then adjust it with water to contain 25% by mass of the bipyridine herbicide to obtain a liquid pesticide Composition: Take 400 parts by mass of liquid pesticide composition, add 20 parts by mass of buffer salt or electrolyte and 20 parts by mass of surfactant, add appropriate amount of water and mix evenly to obtain a liquid pesticide composition herbicide product with a content of 20% for use ;

The preparation method of the solid pesticide composition is as follows: mix 1 mass part of cyclodextrin with 3 mass parts of water, add 0.2 mass part of bipyridyl herbicide, mix well, stir and heat to 60°C under dark conditions , keep warm for 1 hour; evaporate water under reduced pressure at 60°C, then dry under reduced pressure at 50°C to obtain a solid, and pulverize to obtain a powdery inclusion product containing bipyridyl herbicides in a mass percentage of 16.67%; 120 The powdery inclusion product of mass parts is mixed with 4 mass parts of surfactants and 9 mass parts of auxiliary materials, granulated, and dried to obtain a solid pesticide composition herbicide product containing bipyridyl herbicides in a mass percentage of 15%. use.

The beneficial effects of the present invention are:

In general, the pesticide composition of the present invention can be in liquid or solid state, which is convenient to use. The clathrate of bipyridine herbicides has strong activity, stable properties, and long shelf life. It reduces the difficulty of accidental or intentional administration, reduces the randomness of ingestion, reduces the contact injury of humans and animals, and is not easy to spread and pollute the environment. Low.

Specifically, the present invention uses cyclodextrin in the aqueous solution to clathrate paraquat or diquat to directly prepare a liquid pharmaceutical composition, or prepare a stable solid clathrate by removing water and drying the clathrate aqueous solution, and then prepare It can be prepared into a variety of solid dosage forms, and its solid preparation has strong water solubility, and can be mixed with water under the dosage to prepare a true solution. The inclusion state bipyridine herbicide preparation containing cyclodextrin can obtain excellent killing effect at a dosage lower than that of ordinary water preparation. The liquid composition can enhance the drug activity and reduce the dosage of the drug; the solid preparation increases the It is difficult to swallow by mistake, not only convenient to use and transport, but also can significantly improve the weeding effect and reduce the irritation of the product. At the same time, the clathrate preparation does not increase the soil residue, and has good safety to the environment and subsequent crops. The invention can also overcome the molecular association property of paraquat, eliminate or reduce the degree of molecular association, and has great significance for improving the drug effect of paraquat.

Description of drawings

Fig. 1 is: in aqueous solution, the curve graph that paraquat solution ε (measured molar absorption coefficient) continues to decrease with the increase of paraquat concentration c;

Figure 2 is a graph showing that in cyclodextrin solution, paraquat ε fluctuates irregularly with the increase of concentration c, and has a slight upward trend.

Detailed ways

Below in conjunction with specific embodiment and accompanying drawing, the present invention will be further described:

Example 1:

Mix 100 grams of hydroxypropyl-β-cyclodextrin with 200 milliliters of water, stir to dissolve, add 238 milliliters of soluble concentrate of paraquat dichloride (abbreviation: paraquat) (containing 100 grams of paraquat), and mix thoroughly at 60 Stir and keep warm at ℃ for 1 hour, then cool, filter, concentrate (60-90 ml of water is evaporated), add 4 grams of sodium dodecylbenzenesulfonate, 10 grams of polyoxyethylene-polyoxypropylene copolymer, isooctanol poly Add 6 grams of oxyethylene ether, add an appropriate amount of water to a total volume of 500 milliliters, stir and dissolve evenly, and obtain a liquid pesticide composition with a paraquat content of 20%.

Example 2, 5 grams of β-cyclodextrin, 45 grams of hydroxypropyl-β-cyclodextrin and 330 ml of pure water were mixed, stirred and dissolved, and 238 grams of paraquat soluble concentrate (containing 100 grams of paraquat) were added, fully After mixing, stir at 80°C, keep warm at 60°C for 1 hour, cool, filter, add 20 grams of potassium dihydrogen phosphate, 8 grams of sodium lauryl polyoxyethylene ether succinate sulfonate, and 4 grams of polyoxyethylene lauryl ether , 8 grams of isooctyl alcohol polyoxyethylene ether and about 9 milliliters of water are stirred and fully dissolved to obtain a liquid pesticide composition with a paraquat content of 15%.

Example 3, mix 200 g of β-cyclodextrin with 200 ml of pure water, add 106 ml of 42% paraquat soluble concentrate (containing 44.5 g of paraquat), mix well, stir at 80°C, and keep warm at 60°C for 1 Hours later, the water was evaporated and dried under reduced pressure to obtain about 241 grams of powdery solid pesticide composition.

Example 4, mix 200 grams of β-cyclodextrin with 250 milliliters of pure water, add 150 milliliters of 42% paraquat soluble concentrate (containing 63 grams of paraquat), mix well, stir at 80°C, and keep warm at 60°C for 1 Hours later, the water was evaporated at a temperature of 40° C., then dried under reduced pressure, and pulverized to obtain about 260 grams of powdery solid pesticide composition.

Example 5, mix 200 grams of β-cyclodextrin with 200 milliliters of pure water, add 200 milliliters of 42% paraquat soluble concentrate (containing 84 grams of paraquat), mix thoroughly, keep warm at 60°C for 1 hour, and then The moisture was evaporated, and then dried under reduced pressure to obtain about 281 grams of powdery solid pesticide composition.

Example 6, mix 380 grams of β-cyclodextrin with 400 milliliters of pure water, add 100 milliliters of 42% paraquat soluble concentrate (containing 42 grams of paraquat), mix well, keep warm at 60°C for 1 hour, and then The water was evaporated, and then dried under reduced pressure to obtain about 419 grams of powdery solid pesticide composition.

Example 7, mix 252 grams of β-cyclodextrin with 400 milliliters of pure water, add 100 milliliters of 42% paraquat soluble concentrate (containing 42 grams of paraquat), mix well, keep warm at 80°C for 1 hour, and then The moisture was evaporated, and then dried under reduced pressure to obtain about 292 grams of powdery solid pesticide composition.

Example 8 is the same as Example 7, the only difference is that the paraquat is changed to paraquat bisulphate monomethyl ester salt, and the β-cyclodextrin is changed to hydroxypropyl-β-cyclodextrin to obtain about 291 grams Powder clathrate.

Example 9 is consistent with Example 7, except that the β-cyclodextrin is changed to hydroxyethyl-β-cyclodextrin to obtain about 293 grams of powdery solid pesticide composition.

Example 10 is consistent with Example 7, except that the β-cyclodextrin is changed to sulfobutyl-β-cyclodextrin to obtain about 293 grams of powdery solid pesticide composition.

Example 11 is consistent with Example 7, except that paraquat is changed to diquat, and about 291 grams of powdery solid pesticide composition is obtained.

Example 12 is consistent with Example 6, the only difference is that the β-cyclodextrin is changed to a mixed cyclodextrin of 38 grams of β-cyclodextrin and 342 grams of hydroxyethyl-β-cyclodextrin, and about 421 gram of powdery solid pesticide composition.

Example 13 is consistent with Example 6, except that the β-cyclodextrin is changed to a mixed cyclodextrin of 190 grams of β-cyclodextrin and 190 grams of hydroxypropyl-β-cyclodextrin, and about 422 gram of powdery solid pesticide composition.

Example 14, consistent with Example 6, the only difference is: change the β-cyclodextrin to a mixed cyclodextrin of 300 grams of β-cyclodextrin and 80 grams of hydroxybutyl-β-cyclodextrin, and obtain about 421 gram of powdery solid pesticide composition.

Example 15 is consistent with Example 6, the only difference is that the β-cyclodextrin is changed to a mixed cyclodextrin of 38 grams of β-cyclodextrin and 342 grams of hydroxypropyl-β-cyclodextrin, and about 420 gram of powdery solid pesticide composition.

Example 16 is consistent with Example 6, the only difference being: change the mixed cyclodextrin of 342 grams of β-cyclodextrin and 38 grams of sulfobutyl-β-cyclodextrin to obtain about 420 grams of powdery solid pesticide combination.

Example 17, mix 200 g of β-cyclodextrin with 200 ml of pure water, add 200 ml of 42% paraquat soluble concentrate (containing 84 g of paraquat), mix well, stir at 80°C, and keep warm at 60°C for 1 Hours later, the water was evaporated and dried under reduced pressure to obtain a powdery solid pesticide composition. Add 4 grams of sodium dibutylnaphthalene sulfonate, 8 grams of polyoxyethylene lauryl alcohol ether, 2 grams of polyoxyethylene stearyl alcohol ether and 2.8 grams of Tween-80 in the powdery solid pesticide composition, add 35.2 grams of nitric acid simultaneously Ammonium and 84 grams of lactose were uniformly mixed, wet granulated, and dried to obtain a paraquat granule product with a content of 20%.

Example 18, mix 200 g of β-cyclodextrin with 250 ml of pure water, add 200 ml of 42% paraquat soluble concentrate (containing 84 g of paraquat), mix well, stir at 80°C, and keep warm at 60°C for 1 Hours later, the water was evaporated and dried under reduced pressure to obtain a powdery solid pesticide composition. Add 7.8 grams of sodium cetyl sulfonate, 5 grams of polyoxyethylene-polyoxypropylene copolymer, and 4 grams of isooctyl alcohol polyoxyethylene ether into the powdery solid pesticide composition, while adding 10 grams of potassium nitrate and 9 grams of phosphoric acid calcium, uniformly mixed, wet granulated, dried, pulverized and sieved to obtain a paraquat soluble powder product with a content of 26%.

Example 19, mix 189 g of β-cyclodextrin with 200 ml of pure water, add 100 ml of 42% paraquat soluble concentrate (containing 42 g of paraquat), mix well, stir at 80°C, and keep warm at 60°C for 1 Hours later, the water was evaporated and dried under reduced pressure to obtain a powdery solid pesticide composition. Add 2.4 grams of dioctyl sodium sulfosuccinate, 2 grams of isooctyl alcohol polyoxyethylene ether, 2 grams of lauryl alcohol polyoxyethylene ether, and 2 grams of stearyl polyoxyethylene ether in the powdery solid pesticide composition, and simultaneously Add 20 grams of hydroxypropyl cellulose and 20.6 grams of soluble starch, mix evenly, wet granulate, and dry to obtain a paraquat granule product with a content of 15%.

Example 20, mix 189 g of β-cyclodextrin with 200 ml of pure water, add 100 ml of 42% paraquat soluble concentrate (containing 42 g of paraquat), mix well, stir at 80°C, and keep warm at 60°C for 1 Hours later, the water was evaporated and dried under reduced pressure to obtain a powdery solid pesticide composition. The powdery solid pesticide composition is mixed with 4.6 grams of sodium dodecylbenzenesulfonate, 4 grams of polyoxyethylene-polyoxypropylene copolymer, and 4 grams of stearyl polyoxyethylene ether, and then add 20 grams of polyethylene glycol , 30.4 grams of mannitol and 10 grams of potassium dihydrogen phosphate, mixed uniformly, wet granulated, dried, pulverized and sieved to obtain a paraquat soluble powder product with a content of 13.8%.

Example 21, 210 grams of β-cyclodextrin was mixed with 210 milliliters of pure water, 100 milliliters of 42% paraquat soluble concentrate (containing 42 grams of paraquat) was added, mixed thoroughly, stirred at 80°C, and kept at 60°C for 1 Hours later, the water was evaporated and dried under reduced pressure to obtain a powdery solid pesticide composition. Add 3.4 grams of dioctyl sodium sulfosuccinate, 3 grams of isooctyl alcohol polyoxyethylene ether, and 2 grams of stearyl polyoxyethylene ether into the powdery solid pesticide composition, and add 19 grams of soluble starch at the same time, mix well, and wet Granulated by method, and dried to obtain a paraquat granule product with a content of 15%.

The technical characteristics and the verification process that the solid or liquid pesticide composition that above-mentioned embodiment gains are described below in detail:

Inclusion feasibility: The bipyridine cationic structure in aqueous solution has strong ultraviolet absorption at 200nm to 320nm. Adding cyclodextrin which has no ultraviolet absorption itself, the absorbance of the drug increases regularly with the increase of cyclodextrin concentration, indicating that in aqueous solution, cyclodextrin There is an obvious inclusion effect between the essence and the drug. The apparent inclusion constants (Ka) of a series of cyclodextrin-included bipyridine herbicides (1:1) were measured to be 661-1673 L. Ka of dextrin inclusion paraquat = 1434L.mol-1 (pure water, 225-227nm, 15±5°C).

Verification and structure of clathrate: Thermal analysis DTA-TG spectrum of cyclodextrin-paraquat solid clathrate at different ratios shows that endothermic weight loss peak (dehydration) appears at 50-110°C, and exothermic weight loss begins at 210-240°C peak (decomposition of paraquat), its decomposition point is 60-90°C earlier than that of the raw material drug (300°C), and it is also significantly lower than the decomposition point of cyclodextrin, indicating that cyclodextrin-paraquat molecules have produced effective inclusions, After paraquat is embedded in the cyclodextrin cavity and is included, the heterocyclic N and methyl ortho-C atoms are more susceptible to the attack of the adjacent hydroxyl group (the edge of the cyclodextrin cavity), resulting in decomposition.

The 1HNMR spectra of cyclodextrin-paraquat inclusion complexes with different ratios were determined, and it was shown that the C-3 and C-5 protons in the cyclodextrin cavity did not significantly migrate before and after inclusion, indicating that the central bipyridine ring of paraquat in the solution (12 atoms) do not enter the hydrophobic cavity of the cyclodextrin, but are exposed outside the cavity of the cyclodextrin, and the paraquat molecule enters the cavity of the cyclodextrin with a methyl group to form an inclusion complex. The 1H NMR spectra before and after inclusion of diquat showed that the C-3 protons in the cyclodextrin cavity were significantly migrated, and the bispyridine ring part entered the hydrophobic cavity of the cyclodextrin for inclusion.

Product solubility: a series of highly water-soluble cyclodextrin derivatives can be easily prepared into a herbicide inclusion complex aqueous solution with a water content of 50% to 90%, which can be completely dissolved by diluting with water. The solution is for use; the solid clathrate prepared by β-cyclodextrin and mixed cyclodextrin containing β-cyclodextrin also has high water solubility, and the solid clathrate can be quickly dissolved when mixed with water. The clathrate prepared by the less water-soluble β-cyclodextrin can still obtain a true solution at the required dosage concentration, such as: β-cyclodextrin:paraquat 10:1～1:1 solid inclusion compound Paraquat can also be quickly dissolved, and the drug concentration in the solution can reach ³ 530-10700 mg.L ^-1 , both of which are much higher than the highest concentration of paraquat currently used at 1600 mg.L ^-1 .

The aqueous solution prepared by diluting the composition prepared by the invention is a true solution without suspended solid particles in the system, which can effectively prevent the passivation of bipyridyl herbicides and improve the drug activity.

Characteristics of molecular action: Measure the UV absorption of paraquat (pure water and buffer solution) solution and find that: in pure water, with the increase of drug concentration (c), the measured molar absorption coefficient (ε) of the maximum absorption wavelength presents a continuous and continuous decrease, such as As shown in Figure 1, it shows that there is an obvious molecular association phenomenon of paraquat in pure water (Chemical Journal of Chinese Universities, 1993, 14 (6): 766-770), and the precise determination of pure aqueous solution is 0.25～60mg.L-1 (0.25～ 60ppm) interval of paraquat concentration c and ε, calculate ε ⁱ ·ci ^-1 (i=2, 3, 4, 5, 6..., degree of association), substitute i value and use ε to ε ⁱ ·ci ^-1 as Figure, if a straight line is obtained, then the association degree (i) of paraquat in this concentration range can be obtained, and the corresponding equation can be solved for its association constant, and some results are shown in the following table:

The degree of association of paraquat in solution

The measurement results prove that paraquat in aqueous solution has complex molecular association properties. Under pure water conditions, the degree of molecular association increases rapidly with the increase of concentration, and the tri-molecular association of paraquat occurs at very dilute concentration (0.25ppm), 18.7 The association of ten minutes appears in ppm. However, commercially available water agents added with electrolytes or surfactants in the buffer solution do not have a continuous decrease in ε. In the buffer solution with a high proportion concentration (0.1mol.L ^-1 ), only at a low concentration (below 8.88ppm concentration), ε has a continuous downward trend to c, and there is a two-molecular association in the system, but compared with the pure water system, the concentration Higher, and the concentration range is wider; higher than 8.88ppm, there is no continuous downward change of ε with the fluctuation of c, showing that the system has no obvious multi-molecular association. The results suggest that electrolytes, buffer salts and surfactants seem to have the effect of relieving molecular association.

At present, bipyridyl herbicides are applied at relatively high concentrations in practical applications. For example, the concentration of common aqueous paraquat is above 600ppm. Therefore, the phenomenon of drug molecule association is extremely significant, which will produce extremely adverse effects. The association of molecules produces larger association molecules, which will hinder the penetration of drugs into plant membranes, affect the diffusion of drugs, and reduce the efficacy of drugs. The association of a large number of molecules is more likely to lead to the inactivation of drug activity. It can be seen that overcoming the molecular association properties of paraquat and eliminating or reducing the degree of molecular association is of great significance for improving the efficacy of paraquat.

Measure the bipyridine herbicide-cyclodextrin inclusion compound solution prepared by the present invention, or dissolve the bipyridine herbicide with the cyclodextrin solution, and find that with the increase of the drug concentration c, the solution ε (measured molar absorption coefficient) increases with c There is no continuous downward change, but irregular fluctuations and a slight upward trend, as shown in Figure 2. It is suggested that cyclodextrin can significantly change the molecular behavior and existing form of drugs, and the effect is better than that of electrolytes, buffer salts and surfactants. In the solution, due to the spatial constraints of molecular size matching, cyclodextrin can only include a single drug molecule (it is impossible to include more than two drug molecules), and because the actual determination of cyclodextrin inclusion bipyridine herbicides has enough Large inclusion constant, therefore, inclusion greatly reduces the generation of association molecules, increases the concentration of a single free molecule of paraquat, makes it difficult to form association molecules in the solution, thereby improving drug effectiveness and promoting The play of drug activity can effectively prevent the occurrence of drug passivation in the solution.

Further microcalorimetric titration (ITC) tests showed that although the β-cyclodextrin inclusion paraquat in the solution had a large inclusion constant, it only released heat slightly (0.3～1.2kcal.mol ^-1 ), which was significantly lower than the general Drug inclusion heat, and with the increase of titration concentration (450mg.L ^-1 ~ 1800mg.L ^-1 ), the inclusion heat decreases obviously. The lower exothermic effect shows that paraquat molecules in the solution need to absorb energy to overcome the molecular association to achieve inclusion, thus resulting in a decrease in the total heat of inclusion. The thermal effect results suggest that heating during the preparation process can promote the dissociation of association molecules, which will help the formation of inclusion complexes and facilitate the preparation of inclusion products.

Product stability: The cyclodextrin inclusion compound prepared by the present invention can significantly improve the light and thermal stability of the product. Compared with the existing water preparation, the inclusion compound prepared by non-ionized cyclodextrin has a half-life of light and thermal decomposition Respectively increased by 15% to 35%, the clathrate of cyclodextrin ionized derivative sulfobutyl-β-cyclodextrin has the strongest light and thermal stability, and its light and thermal decomposition half-life is more than twice that of the water agent.

Weed-killing activity: the present invention finds that inclusion can greatly improve the activity of bipyridyl herbicides; the activity of the solid preparation prepared with a low inclusion ratio is equivalent to that of the commercially available water preparation (adding 30% surfactant).

Potted weed killing test: Cyclodextrin inclusion paraquat (paraquat:cyclodextrin mass ratio 1:0.5～1:9) has obvious synergistic effect, with the increase of cyclodextrin ratio, its synergistic effect enhanced. The clathrate solution with a mass ratio of 1:2 can enhance the activity by more than 30% (1200ppm clathrate solution is equivalent to the activity of 1600ppm raw material). The solid clathrate of equimolar cyclodextrin (embodiment 3) and 42% paraquat raw material contrast test, two samples add water and dilute respectively to obtain each series of solutions of paraquat concentration 350ppm, 700ppm and 1600ppm, spray potted weeds with solution, The following results are obtained:

Weed killing rate of paraquat and clathrate at each drug concentration

Field Weed Killing Test:

The 20% paraquat granules prepared by the present invention (Example 17), the paraquat 26% soluble powder (Example 18) and the commercially available 20% paraquat water were compared for field tests, and the test site was weeds in the ditch of the wheat field The test objects were Lagopsis supina (Steph.ex Willd.) Ik.-Gal), Capsella bursa-pastoris and Stellaria media (Linn.) Cyr.

WS-16P knapsack manual sprayer, the working pressure is 0.2-0.3Mpa, and the nozzle diameter is 1mm. Spray evenly with a hand sprayer after the dew dries on a sunny day. The spray volume is 450kg/hm ² , and the spray concentration is 500-2000ppm. In the field test, 5 days, 7 days, and 15 days after application, weed poisoning and symptoms were observed in each treatment area, and the amount of remaining weeds was investigated. According to the regulations in the "Pesticide Field Efficacy Test Guidelines (1)", control effect statistics and calculation of correction drugs were carried out. effect.

The calculation results using the DMRT method show that the corrected control efficacy of the two paraquat pesticides in the field test for controlling summer solstice, shepherd's purse and chickweed in the concentration range of 450 g/ha to 600 g/ha for 15 days both reached 90%. Above, and within this concentration range, the control effects on weeds of the two solid preparations after 15 days of application are not significantly different from those of the control drug 20% paraquat water solution. Below the recommended dose of 450 g/ha in the field test, the difference in the control effect of three pesticides with the same concentration of weeds was not significant.

According to field test results, the recommended dosage of the solid preparation prepared by the present invention is within the series concentration range of 450-600 g/ha, and a relatively ideal weeding effect can be achieved when the spray concentration is 1000 ppm.

Product Safety:

Irritation test: bipyridyl herbicides have obvious eye and skin irritation, and the solid preparation prepared with cyclodextrin inclusion compound can greatly alleviate the irritation. According to the toxicological test method for pesticide registration (GB15670-1995), the The 20% paraquat inclusion solid granule prepared by the invention (Example 17) was compared with the commercially used paraquat liquid preparation for skin and eye irritation comparison tests. The solid granule of the present invention has no eye irritation and no skin irritation; Commonly used liquid preparations have moderate eye irritation and mild skin irritation. The irritation of the solid granules prepared by the invention is significantly improved.

3631)，样品：包合物(β-环糊精-百草枯9：2质量比)，市售20％百草枯水剂，纯水(空白对照)。结果如下表：Soil drug residue test: bioassay method to detect paraquat residue test in soil (SAC-WB method, J.Agric.Food Chem.2002, 50,

3631), sample: clathrate (β-cyclodextrin-paraquat 9:2 mass ratio), commercially available 20% paraquat water solution, pure water (blank control). The results are as follows:

Both the common 20% paraquat aqueous solution and the inclusion compound inhibited the growth of the tested wheat roots, and the inclusion compound was slightly lower than the common paraquat aqueous solution (the drug residue was smaller), but there was no significant difference in the inhibitory effect. The results showed that the inclusion of cyclodextrin did not increase paraquat residues or aggravate its toxicity, and it was safe to soil and subsequent crops.

Claims (10)

1. solid or the liquid pesticide compositions of cyclodextrin and bipyridyl herbicides inclusion compound, is characterized in that: comprise that mass ratio is bipyridyl herbicides and the cyclodextrin of 1:0.5～1:9.

2. solid or the liquid pesticide compositions of cyclodextrin according to claim 1 and bipyridyl herbicides inclusion compound, is characterized in that: the mass ratio of described bipyridyl herbicides and cyclodextrin is 1:1～1:6.

3. solid or the liquid pesticide compositions of cyclodextrin according to claim 2 and bipyridyl herbicides inclusion compound, is characterized in that: the mass ratio of described bipyridyl herbicides and cyclodextrin is 1:4.5.

4. according to the cyclodextrin described in claim 1,2 or 3 and solid or the liquid pesticide compositions of bipyridyl herbicides inclusion compound, it is characterized in that: described bipyridyl herbicides is the two methyl sulfate salt of paraquat dichloride, paraquat or diquat dibromide; Described cyclodextrin is the hybrid ring dextrin that single cyclodextrin or multiple single cyclodextrin form, wherein, described single cyclodextrin is beta-schardinger dextrin-, HP-β-CD, hydroxyethyl-β-cyclodextrin, hydroxyl fourth group-beta-cyclodextrin or sulphur fourth group-beta-cyclodextrin, and described hybrid ring dextrin comprises that mass percent is 10～90% beta-schardinger dextrin-.

5. solid or the liquid pesticide compositions of cyclodextrin according to claim 4 and bipyridyl herbicides inclusion compound, is characterized in that: described bipyridyl herbicides is paraquat dichloride.

6. according to the cyclodextrin described in claim 1,2 or 3 and solid or the liquid pesticide compositions of bipyridyl herbicides inclusion compound, it is characterized in that: described solid or liquid pesticide compositions also comprise that mass percent is 10%～30% surfactant, and described surfactant is ionic and/or nonionic; Described ionic surfactant is selected from: laureth succinate sodium sulfonate, neopelex, sodium cetanesulfonate, dioctyl sodium sulfosuccinate and nekal; Described nonionic surface active agent is selected from: Pluronic F68, isooctanol APEO, Dodecyl Polyoxyethylene Ether, polyoxyethylene octadecanol and twen-80.

7. solid or the liquid pesticide compositions of cyclodextrin according to claim 6 and bipyridyl herbicides inclusion compound, is characterized in that: described surfactant is mixed and forms with 2～3 kinds of described nonionic surface active agent by a kind of described ionic surfactant; The mass ratio of described ionic surfactant and described nonionic surface active agent is 2:(0～5).

8. solid or the liquid pesticide compositions of cyclodextrin according to claim 7 and bipyridyl herbicides inclusion compound, is characterized in that: described solid or liquid pesticide compositions also add pharmaceutical auxiliary agent or auxiliary material; Wherein, in described liquid pesticide compositions, adding quality is 0～20% buffer salt or electrolyte of described liquid pesticide compositions quality, and described buffer salt is potassium dihydrogen phosphate, and described electrolyte is ammonium nitrate, potassium nitrate or calcium phosphate; In described solid pesticide compositions, adding quality is 0～120% L-HPC, soluble starch, lactose, polyethylene glycol or mannitol of described solid pesticide compositions quality, and preparation becomes solid pharmaceutical preparation.

9. cyclodextrin and the solid of bipyridyl herbicides inclusion compound or a preparation method for liquid pesticide compositions, is characterized in that: comprise the following steps:

(1) cyclodextrin of 9 mass parts is mixed with the water of 9～63 mass parts, add the bipyridyl herbicides of 1～18 mass parts, fully mix;

(2) under lucifuge condition, heat 60～80 ℃, stir, make system completely evenly or dissolve, be then incubated 1 hour;

(3) system that is dissolved as solution completely of step (2) gained is cooled to room temperature, filter, concentrated, measure paraquat actual content and with water, be adjusted to desired concn again, must comprise mass percent and be the liquid pesticide compositions of 10%～25% bipyridyl herbicides; By step (2) gained evenly or the system of dissolving at 60 ℃ of temperature, steams and removes moisture content, then drying under reduced pressure obtains solid at 50 ℃, pulverizes and obtain to comprise the powdery solid composition pesticide that mass percent is 10%～30% bipyridyl herbicides.

10. preparation method according to claim 9, it is characterized in that: the preparation method of described liquid pesticide compositions is as follows: the highly-water-soluble cyclodextrin of 1 mass parts is mixed with the water of 2 mass parts, the bipyridyl herbicides that adds 1 mass parts, fully mix, under lucifuge condition, be heated to 60 ℃, stir, system is dissolved, be then incubated 1 hour; Solution is cooled to room temperature, filters, concentrated, measure paraquat actual content, then take water and be adjusted to containing bipyridyl herbicides mass percent to be 25%, to obtain liquid pesticide compositions; The liquid pesticide compositions of getting 400 mass parts adds the buffer salt of 20 mass parts or the surfactant of electrolyte and 20 mass parts, add liquid pesticide compositions weed killer herbicide product that suitable quantity of water mixed and obtained content 20% for;

The preparation method of described solid pesticide compositions is as follows: the cyclodextrin of 1 mass parts is mixed with the water of 3 mass parts, add the bipyridyl herbicides of 0.2 mass parts, fully mix, be heated with stirring to 60 ℃ under lucifuge condition, be incubated 1 hour; At 60 ℃ of temperature, remove moisture content under reduced pressure, then drying under reduced pressure obtains solid at 50 ℃, the powdery inclusion product that to pulverize and obtain containing bipyridyl herbicides mass percent be 16.67%; This powdery inclusion product of 120 mass parts mixes with the surfactant of 4 mass parts, the auxiliary material of 9 mass parts, granulates, dry the solid pesticide compositions weed killer herbicide product that is 15% containing bipyridyl herbicides mass percent for.

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