CN113197200B

CN113197200B - Preparation method and application of gel drug-loading system with pesticide molecule hymexazol as gelling agent

Info

Publication number: CN113197200B
Application number: CN202110482027.9A
Authority: CN
Inventors: 曹立冬; 许春丽; 黄啟良; 曹冲; 赵鹏跃; 李凤敏
Original assignee: Institute of Plant Protection of Chinese Academy of Agricultural Sciences
Current assignee: Institute of Plant Protection of Chinese Academy of Agricultural Sciences
Priority date: 2021-04-30
Filing date: 2021-04-30
Publication date: 2022-04-08
Anticipated expiration: 2041-04-30
Also published as: CN113197200A

Abstract

The invention discloses a preparation method and application of a gel drug-loading system with pesticide molecule hymexazol as a gelling agent, wherein the preparation method comprises the following steps: step A: placing carboxymethyl chitosan CMCS and sodium alginate SA in the same container, adding water, and stirring until completely dissolving to obtain a mixed solution CA; and B: preparing hymexazol into hymexazol solution Hy; and C: and mixing the mixed solution CA and the hymexazol solution Hy, and uniformly stirring to obtain a hydrogel drug-loading system. The application of the pesticide molecule hymexazol as a gel drug-loading system of a gelling agent comprises the following steps: the gel drug-loaded system prepared by the preparation method is used for loading pesticide active ingredients. The hymexazol hydrogel drug-loading system prepared by the invention can enhance the adhesiveness of hydrophilic pesticide hymexazol at a target part, fully exert the atom economy of a carrier material, and reduce the loss of pesticide caused by rain wash and the like, thereby improving the utilization rate of the drug.

Description

Preparation method and application of gel drug-loading system with pesticide molecule hymexazol as gelling agent

Technical Field

The invention relates to the technical field of preparation of gel drug-loaded systems. In particular to a preparation method and application of a gel drug-loading system with pesticide molecule hymexazol as a gelling agent.

Background

The intelligent pesticide sustained and controlled release system is one of effective ways for improving the pesticide effectiveness and utilization rate and prolonging the lasting period in the current agriculture. Along with the continuous development of pesticide formulations and the cross fusion between different subject fields, a water-based gel system taking a high molecular polymer as a carrier material attracts attention. As a semi-solid carrier material, the hydrogel not only can absorb and retain a large amount of water, but also can load active ingredients such as fertilizers and pesticides and release the active ingredients slowly and continuously, and plays an important role in the field of soilless culture in modern agriculture. However, most of the currently widely studied hydrogel drug-loading systems are high molecular polymer hydrogels prepared by a chemical crosslinking method, which not only have higher cost, but also have certain pressure on the environment. Therefore, the hydrogel is prepared by taking the cheap and easily-obtained degradable natural high molecular compound as a substrate material and not adding or adopting the effective component with the gelling effect as a cross-linking agent, so that the cost can be reduced, the effect of fully realizing the atom economy of the carrier material can be achieved, and the hydrogel has important significance for the use and development of pesticides in modern agriculture.

It has been reported that natural polymer-based compounds such as sodium alginate, chitosan and its derivatives, guar gum, starch, folic acid, etc. can form hydrogel systems through covalent bonds or non-covalent bonds (hydrogen bonding, pi-pi stacking, electrostatic interactions, van der waals interactions, dipole-dipole interactions, coordination interactions, etc.). According to the synthesis means and properties of the hydrogel, the hydrogel drug-loaded system can be divided into a high-molecular hydrogel drug-loaded system and a supramolecular hydrogel drug-loaded system. Compared with the traditional covalent bond polymer hydrogel, the supermolecule hydrogel self-assembles low molecular weight gelling agent molecules into three-dimensional grids with various nano structures through non-covalent interaction, so that solvent water molecules are immobilized. The supermolecule hydrogel has more intelligent and stronger application potential in aspects of subject-object chemistry, bio-organic chemistry, molecular devices, liquid crystal materials and the like.

The hymexazol (hymexazol) has a chemical name of 3-hydroxy-5 methyl-isoxazole, is a new generation of novel pesticide bactericide, and is a systemic pesticide suitable for trees, wheat, cotton, rice and the like. The hymexazol can effectively inhibit or kill pathogenic fungi mycelium fungicide and soil disinfectant, belongs to green, environment-friendly, low-toxicity and pollution-free products, is suitable for crop fruits, and has the effects of promoting plant growth, promoting crop root growth and development, rooting and strengthening seedlings and the like. As a hydrophilic pesticide, hymexazol is easy to prepare into a water-based dosage form, but due to the hydrophilicity, hymexazol is easy to be washed away with water in the environment, so that the pesticide effect is lost, and the waste of the pesticide is caused.

The alginate is a natural anionic polymer, is mainly extracted from brown algae in the ocean, and has good biocompatibility and biodegradability. The alginate is a copolymer with L-guluronic acid (G) and D-mannuronic acid (M) as structural units, and the chain segments can be continuous G chain segments (GGGGG) and M chain segments (MMMMM) or alternate MGMG chain segments. Carboxymethyl chitosan is a zwitterionic polymer, is a carboxymethylation product of chitosan, has the excellent performance of chitosan, and shows good water solubility.

Disclosure of Invention

Therefore, the technical problem to be solved by the invention is to provide a preparation method and application of a gel drug-loading system using pesticide molecule hymexazol as a gelling agent, so as to solve the problem that pesticide such as hymexazol is easy to run off along with water washing to cause drug effect reduction.

In order to solve the technical problems, the invention provides the following technical scheme:

the preparation method of the gel drug-loading system with pesticide molecule hymexazol as the gelatinizer comprises the following steps:

step A: placing carboxymethyl chitosan CMCS and sodium alginate SA in the same container, adding water, and stirring until completely dissolving to obtain a mixed solution CA;

and B: dissolving hymexazol in solvent to prepare hymexazol solution Hy;

and C: and mixing the mixed solution CA and the hymexazol solution Hy, and uniformly stirring to obtain a gel drug-loaded system.

In the step A, the carboxymethyl chitosan CMCS is O-carboxymethyl chitosan; the relative molecular mass of the carboxymethyl chitosan CMCS is 10-20 ten thousand.

In the step A, the purity of the sodium alginate SA is more than or equal to 99 wt%.

In the step A, the mass ratio of the carboxymethyl chitosan CMCS to the sodium alginate SA is 9: 1-1: 9; the mass concentration of the mixed solution CA is 2-20 mg/mL.

In the step B, the solvent used for preparing the hymexazol solution Hy is water, methanol or ethanol; the mass concentration of the hymexazol solution Hy is 0.5-10 mg/mL; the purity of the hymexazol is greater than or equal to 98 wt%.

In the step C, the volume ratio of the mixed solution CA to the hymexazol solution Hy is 1: 2-8: 1.

According to the preparation method of the gel drug loading system with pesticide molecule hymexazol as a gelling agent, the mass ratio of carboxymethyl chitosan CMCS to sodium alginate SA is 1:1, the concentration of the mixed solution CA is 20mg/mL, the concentration of hymexazol solution Hy is 10mg/mL, and the volume ratio of the mixed solution CA to hymexazol solution Hy is 2: 1.

In the preparation method of the gel drug-loading system with the pesticide molecule hymexazol as the gelling agent, in the step B, the pesticide which can be dissolved in the solvent is added into the hymexazol solution Hy.

In the step B, the pesticide is: one or two or more of mixed aqueous solution or alcoholic solution of dicamba, glyphosate, glufosinate and imidacloprid, or one or two or more of alcoholic solution of 2,4-D, pyrithiobac-sodium, nitenpyram, indoxacarb, tricyclazole, propiconazole, epoxiconazole, fludioxonil, azoxystrobin, pyraclostrobin, tebuconazole, thifluzamide, difenoconazole, prothioconazole or prochloraz; the alcohol solution is a methanol solution or an ethanol solution.

The application of the pesticide molecule hymexazol as a gel drug-loading system of a gelling agent is to use the gel drug-loading system prepared by the preparation method for loading pesticide active ingredients.

The technical scheme of the invention achieves the following beneficial technical effects:

(1) the invention adopts alginate and chitosan derivative O-carboxymethyl chitosan as carrier materials, and pesticide active ingredient hymexazol as gelling agent, so as to obtain gel drug-loading systems with different performances suitable for various scenes; the hymexazol is used as a gelatinizing agent to prepare a novel gel drug-loading system, so that the adhesion of hydrophilic pesticide hymexazol at a target part can be enhanced, the atom economy of a carrier material is fully exerted, and the loss of pesticide caused by rain wash and other reasons is reduced, thereby improving the utilization rate of the drug.

(2) The hymexazol hydrogel prepared by the invention has good thixotropy, can ensure that the gel has better adhesiveness due to increased viscosity when being sprayed on the surface of a plant, can better resist the washing of external force action such as rainwater, wind power and the like, reduces the loss of a medicament, and improves the medicament effect.

(3) The hymexazol hydrogel prepared by the invention has the advantages that the loading rate of the hymexazol is close to 100 percent, and the drug effect of the hymexazol is ensured; simultaneous HYG_B1And HYG_B2The hydrogel prepared by the method has good stability, and is not easy to be washed and lost due to dissolution in rainwater after being washed by rainwater; in addition, leaching tests also prove that in the hymexazol gel drug-loading system, the hymexazol and the carrier material have good combination effect, and can be adhered to a target interface and not easy to be washed away by rainwater. Through testing the bacteriostatic performance of the hydrogel, the hydrogel HYG is found_B1The method can effectively inhibit sclerotinia sclerotiorum, which shows that the hydrogel prepared by the invention retains the biological activity of hymexazol and has obvious drug effect.

(4) The hymexazol hydrogel medicine carrying system prepared by the invention has the loss amount of 43 percent and 54 percent respectively on cucumber leaves and a hydrophobic membrane after rainwater simulation washing, and the hymexazol water agent sold in the market can be completely washed away, and the washing rate is 100 percent, which shows that the gel medicine carrying system can be better attached to an interface, and the probability of being washed away by rainwater is reduced. In addition, when the hydrogel prepared by the invention is sprayed on an interface, the phenomena of bouncing and crushing are not easy to occur, and the drug loss caused by the splashing of liquid drops due to impact force is reduced.

(5) When the hymexazol gel drug-loading system is prepared, other various pesticides can be added according to the disease requirements of crops, and the gel drug-loading system with the rain washing prevention effect and good stability can be prepared.

Drawings

FIG. 1 hydrogel HYG of the invention_A1、HYG_B1And photographs of the CA solution;

FIG. 2 hydrogel HYG with allura red of the present invention_A1、HYG_B1、HYG_C1The photograph of (a);

FIG. 3 HYG of the present invention_A1Scanning electron micrograph (100 μm);

FIG. 4 HYG of the present invention_B1Scanning electron micrograph (100 μm);

FIG. 5 HYG of the present invention_C1Scanning electron micrograph (100 μm);

FIG. 6 HYG of the present invention_A1Scanning electron micrograph (10 μm);

FIG. 7 HYG of the present invention_B1Scanning electron micrograph (10 μm);

FIG. 8 HYG of the present invention_C1Scanning electron micrograph (10 μm);

FIG. 9 HYG of the present invention_A1、HYG_B1、HYG_C1Test results of stress dependence (f ═ 1 Hz);

FIG. 10 HYG of the present invention_A1、HYG_B1、HYG_C1The frequency dependence of the oscillation profile (stress of 1Pa) was measured;

FIG. 11 HYG of the present invention_A1、HYG_B1、HYG_C1The shear viscosity of (d);

FIG. 12 HYG of the present invention_A1、HYG_B1、HYG_C1The strain induced damage and self-healing performance test results;

FIG. 13 hydrogel HYG of the present invention_D2Photographs after injection into pure water;

FIG. 14 hydrogel HYG of the present invention_D2Gel fixation pattern after injection onto a substrate;

FIG. 15 shows the different mass ratios of CMCS to SA according to the invention,Phase transition of hydrogel formed by different volume ratios of CA and Hy (C)_Hy＝10mg/mL、C_CA＝20mg/mL)；

FIG. 16 shows the phase transition of the hydrogel formed by different mass ratios of CMCS to SA and different volume ratios of CA to Hy according to the present invention (C)_Hy＝5mg/mL、C_CA＝20mg/mL)；

FIG. 17 shows the phase transition of the hydrogel formed by different mass ratios of CMCS to SA and different volume ratios of CA to Hy according to the present invention (C)_Hy＝10mg/mL、C_CA＝10mg/mL)；

FIG. 18 shows the phase transition of the hydrogel formed by different mass ratios of CMCS to SA and different volume ratios of CA to Hy according to the present invention (C)_Hy＝5mg/mL、C_CA＝10mg/mL)；

FIG. 19 shows the ratio of the amounts of hymexazol to an aqueous solution of an equivalent amount of hymexazol in the hydrous gel of the present invention;

FIG. 20 HYG of the present invention_A1、HYG_A2、HYG_B1And HYG_B2Maximum swelling ratio of hydrogel in 0.01M PBS solution at different pH (pH 3.23, 5.34, 7.24, 9.04, respectively);

FIG. 21 HYG of the present invention_A1、HYG_A2、HYG_B1And HYG_B2Maximum swelling ratio of hydrogel in 0.1M PBS solution at different pH (pH 3.23, 5.34, 7.24, respectively);

FIG. 22 is a graph showing the bacteriostatic results of different treatment groups of the present invention against pathogenic bacteria;

FIG. 23 shows the results of measurement of leaching properties of hydrogel soil according to the present invention;

FIG. 24 shows the results of the washing of the water-repellent PTFE film and the cucumber leaf surface with the water-gel of the present invention and hymexazol water (TJX);

FIG. 25 is a photograph of the water gel of the present invention and hymexazol water aqua (TJX) before simulating rainwash on the surfaces of PTFE hydrophobic membrane and cucumber leaf;

FIG. 26 is a photograph of the PTFE hydrophobic membrane and cucumber leaf surface after simulated rain washing with the hydrogel and hymexazol water aqua (TJX) of the present invention;

FIG. 27 measurement of drop bounce behavior for different treatment groups according to the invention.

Detailed Description

1. Materials and methods

Materials: the relative molecular mass of the O-carboxymethyl chitosan is 10 to 20 ten thousand; sodium alginate with the purity of 99 wt% and the viscosity of more than or equal to 0.02(10 g/L)/Pa.s; hymexazol, purity of 98 wt%; the water used was ultrapure water, and the other reagents were analytical grade.

1.1 preparation method of hydrogel drug-loading

Respectively weighing a certain amount of carboxymethyl chitosan (CMCS) and Sodium Alginate (SA), putting the weighed CMCS and Sodium Alginate (SA) into the same beaker in proportion, wherein the weight ratio of CMCS to SA is 9: 1. 4:1, 3:1, 1:3, 1:4, 1:9 preparing 7 groups of samples, adding a proper amount of ultrapure water into the mixed sample of the CMCS and the SA, and stirring by using a magnetic stirrer until the ultrapure water is completely dissolved to obtain a mixed solution (CA), wherein the adding amount of the ultrapure water is such that the concentration of each group of CA solution respectively reaches 2, 5, 10 and 20 mg/mL; using hymexazol as gelatinizer, respectively preparing hymexazol water solution (Hy) with mass concentration of 0.5, 1, 2, 5, 10 mg/mL; mixing the CA solution and the Hy solution according to different proportions, and uniformly mixing to obtain a hydrogel drug-loading system; the volume ratio of the CA solution to the Hy solution is 1:2, 1:1, 2:1, 4:1 and 8:1 respectively.

In this example, the hydrogel drug-loaded system is simply referred to as "hydrogel". CMCS: SA ═ 1:1, (m/m), CA: 3 of the hydrogels prepared under Hy ═ 2:1(v/v) were named HYG_A1、HYG_B1、HYG_C1The specific ratios of the components in the above-mentioned 3 kinds of hydrogels and other several kinds of hydrogels are shown in table 1.

TABLE 1

1.2 stability determination of hydrogels

In the invention, hymexazol is used as a gelling factor in hydrogel to participate in the synthesis of gel. In order to examine whether the stability of hymexazol in the gel is changed, the content of hymexazol before and after gelling is measured in the embodiment. Taking a certain mass of hydrogel, and adding 0.2M NaHCO₃Dissolving with 0.06M sodium citrate solution, and detecting by high performance liquid chromatographyContent of hymexazol in the gel. The content of hymexazol in the hydrogel is calculated according to a standard curve y of hymexazol in methanol solution of 0.3645x-3.3729(R2 is 0.9999). The method comprises the steps of dividing the content of the hymexazol detected in the gel by an equal amount of the hymexazol to obtain a detectable amount of the hymexazol, and verifying whether the hymexazol exists stably in the hydrogel.

1.3 sample characterization of hydrogels

And dripping the hydrogel on a silicon wafer, freezing and drying, and then adhering the hydrogel on a conductive adhesive for gold spraying. Scanning electron microscopy (SEM, SU8010, hitachi ltd, tokyo, japan, operating voltage 20.0kV) was used to characterize the morphology of the resulting hydrogel.

The rheological properties of the hydrogels were evaluated using an MCR301 rheometer. The rheometer was equipped with 20mm parallel plates at 25 + -0.1 deg.C. Dynamic strain sweep spectra were studied at a frequency of 1Hz over a range of 0.1-100pa of dynamic strain sweep. The dynamic frequency sweep spectrum of the gel is obtained from the linear viscoelastic state of the hydrogel determined from the dynamic stress sweep measurement, i.e. when the strain is 1pa, the dynamic frequency sweep range is 0.1-10 Hz. The dynamic oscillation measurement of the gel was carried out at 1% strain and 1Hz with a shear rate from 1s^-1Increased to 10s^-1Immediately followed by a shear rate of from 10s^-1Down to 1s^-1. An oscillatory strain test is alternately carried out by adopting small strain (0.1%) and large strain (200%) at the frequency of 2Hz, and the strain-induced damage and self-healing performance of the hydrogel to the applied stress are examined.

1.4 measurement of swelling value of hydrogel

The swelling value (SR) was used to further evaluate the pH responsiveness of the hydrogel particles prepared. Briefly, a predetermined weight of the sample was immersed in a buffer solution having a pH of 3 to 9 at room temperature, and then the swollen hydrogel particles were taken out of the solution at intervals, weighed after the surface water was blotted with filter paper, and then put back into the solution. All experiments were repeated three times. The Swelling Ratio (SR) was calculated according to the following equation.

Wherein, W_sAnd W_dThe weights of swollen hydrogel and dry hydrogel are indicated, respectively.

This example uses HYG_A1、HYG_A2、HYG_B1And HYG_B2Four different hydrogels were used as test subjects.

1.5 hydrogel bacteriostatic property test

The antagonism of the hydrogel to sclerotinia sclerotiorum is determined by adopting a plate confronting method. The cultured sclerotinia rot of colza colony is punched with a punch (diameter 5mm) and the cake is picked and placed in the center of PDA plate. A hole with the diameter of 5mm is punched at the position of 2cm left and right of the fungus cake by a puncher respectively, and the test groups are as follows:

1) blank control CK: respectively using a liquid transfer gun to transfer 0.6mL of sterile water into holes on the left side and the right side of the bacterial cake;

2) test group a: respectively using a pipette to pipette 0.2mL of CA solution with the concentration of 10mg/mL into the holes on the left side and the right side of the bacterial cake;

3) test group B: obtaining dried hydrogel HYG with diameter of 5mm with a puncher_B1And placing the mixture at the position of 2cm left and right of the fungus cake.

4) Test group C: 0.2mL of hydrogel HYG was pipetted separately with a pipette_B1Directly injecting into the holes at the left and right sides of the fungus cake without drying.

The PDA plates treated in different ways are cultured at a constant temperature of 25 ℃, when the contrast colonies in the plates are nearly full, the test group plates are observed to have an antibacterial band, and each treatment is repeated for 3 times.

1.6 measurement of interfacial flow Rate of hydrogel

Selecting fresh cucumber leaf and PTFE hydrophobic membrane with the same size, spreading in a watch glass, and adding hymexazol hydrogel HYG with effective component concentration of 1mg/mL_C3Uniformly dripping the solution on cucumber leaves and a hydrophobic membrane, and naturally drying. Then, the watch glass is placed to form an included angle of 30 degrees with the table top, and 1.5mL of deionized water is used for washing the blade and the PTFE hydrophobic membrane for three times; collecting washing liquid with commercial hymexazol aqueous solution (TJX) as control group, filtering with filter membrane, and collecting filtrateAnd measuring the content of hymexazol by high performance liquid chromatography.

1.7 hydrogel bouncing Property measurement

This embodiment sets a groups: pure water, group B: 5mg/mL CA solution, group C: 5mg/mL of Tujunxiao (TJX) solution, group D: 5mg/mL of hymexazol aqueous solution, and group E: HYG_D1And group F: HYG_D2And group G: HYG_D3(ii) a The ultra-high speed camera is fixed and connected with a computer, the injector is fixed on the tripod, the falling height of the liquid drop is adjustable, and the collision speed of the liquid drop is controlled by adjusting the height of the injector. The liquid drops all fall from the height of 40cm, and the surface of the PTFE hydrophobic membrane is horizontally placed at the bottom of the platform. The collision and bounce process of the liquid drop on the target interface is captured at the falling moment of the liquid drop.

1.8 determination of leaching Performance of hydrogel soil

Collecting soil from the test field, wherein the sampling depth is 0-15 cm. Drying in shade, sieving with sieve with diameter of 2mm, and storing at room temperature; filling the air-dried soil into a glass column (20 cm in length and 2.5cm in diameter), wherein the height of the filled soil column is 12cm, and the bottom of the soil column is filled with glass wool; mixing hydrogel HYG_A1Placing on a soil column, then covering with air-dried soil with the thickness of 1cm, and filling the top with quartz sand; and controlling the leaching speed by using a peristaltic pump, adjusting the flow rate to be 1mL/min, and performing a soil leaching test. Commercial hymexazol Granules (GR) were used as a control in this experiment. In the test, when 10mL of leaching solution is collected, the leaching condition of hymexazol is determined by adopting a high performance liquid chromatography, and the accumulated leaching amount is calculated according to the following formula:

E_lthe accumulated leaching amount (%) of hymexazol in the soil leaching solution after the test; ve is the volume of the drench solution (10mL) per sampling time; cn is the concentration (mg/mL) of hymexazol in the soil leaching solution within the sample time n; m is_pesticideThe administration amount (mg) of hymexazol is adopted.

2. Test results

2.1 characterization of the hydrogels

FIG. 1 and FIG. 2 are respectively HYG_A1、HYG_B1And CA solution and HYG with addition of allura red_A1、HYG_B1And HYG_C1The digital photograph of (1). After gelation, the gel was seen to solidify at the bottom of the tube when inverted, and the CA solution settled to the bottom by gravity when inverted. When the allura red is added to the hymexazol water solution, the solution can still produce gel after being mixed, and is not influenced by the added components. The results also indicate that the gel remains stable when other ingredients are added to the hydrogel, further indicating that the hydrogel can be used as a carrier to carry other active ingredients.

In addition, it has been tested that adding water-soluble pesticides such as dicamba, glyphosate, glufosinate, imidacloprid, etc. to the hymexazol aqueous solution can form hydrogel. The gel can also be generated by adding methanol or ethanol solutions of 2,4-D, pyrithiobac-sodium, nitenpyram, indoxacarb, tricyclazole, propiconazole, epoxiconazole, fludioxonil, azoxystrobin, pyraclostrobin, tebuconazole, thifluzamide, difenoconazole, prothioconazole, prochloraz and the like into the hymexazol aqueous solution. Further, when the solvent of the hymexazol solution is replaced with ethanol or methanol, a gel may still be formed, and a gel may also be formed by adding the above-mentioned agricultural chemical or various agricultural chemicals soluble in the above-mentioned solvent.

FIG. 3 and FIG. 6 are HYG_A1The gel of (2) is scanned by electron microscope, and FIGS. 4 and 7 are HYG_B1The gel of (2) is scanned by electron microscope, and FIGS. 5 and 8 are HYG_C1Scanning electron micrograph of the gel. As can be seen from the above figure, the hydrogel lattice is denser with increasing CA, and the flowable hydrogel lattice structure formed at low concentrations is more porous.

As shown in FIG. 9, the elastic modulus G 'of the hydrogels prepared at different concentration ratios is larger than the viscous modulus G'. When the concentration of the CA is increased to 20mg/mL from 5mg/mL, the elastic modulus G' is increased by 1 order of magnitude, and the yield value is also increased, which shows that the increase of the density of the carrier material CA has a larger influence on the enhancement of the mechanical property of the hydrogel, and the strength of the hydrogel is enhanced along with the increase of the carrier material. Under stressThe hydrogel showed less dependence on frequency in the frequency range of 0.1-1Hz at 1Pa (see FIG. 10), indicating that the viscoelastic properties of the hydrogel were more stable. In addition, the viscosity test in FIG. 11 shows that the shear rate is changed from 0.1s^-1Increased to 10s^-1The viscosity of the hydrogel showed a decreasing trend as a whole, indicating that all 3 hydrogels prepared in this example had good shear thinning behavior. In addition, as can be seen from fig. 12, the hydrogel has good strain-induced damage and self-healing properties, the elastic modulus G' and the viscous modulus G ″ recover almost completely within 30s, and the recovery behavior can be repeated many times, showing rapid self-healing properties.

FIGS. 13 and 14 show that when the concentration of CA solution is 2mg/mL and the concentration of Hy solution is 2mg/mL, respectively, and allure red hydrogel HYG is added during the preparation process_D2The pictures were injected into water and on the substrate. The hydrogel can be injected to an aqueous solution and a substrate material through an injector, the thixotropy of the hydrogel is demonstrated, when pesticide liquid is sprayed through a nozzle hole, liquid drops are formed under high shear pressure, and the hydrogel is expected to be used in ultra-low volume sprays and can be suitable for spraying by an unmanned aerial vehicle.

2.2 phase transition of hydrogels

FIG. 15 is a phase transition of hydrogel formed when the concentration of Hy solution is 10mg/mL, the concentration of CA solution is 20mg/mL, and the mass ratio of CMCS to SA is different, the volume ratio of CA solution to Hy solution being different; as can be seen in fig. 15, as the SA content increased, the hydrogel gradually changed from a non-flowable hydrogel to a flowable hydrogel. When the CMCS: SA 1: at 3(m/m), no hydrogel is formed. It is assumed that the repulsion between CMCS and the side chain carboxyl group of SA, the interaction between the molecule and hymexazol, and the hydrogen bond between the molecules cancel each other, and therefore no hydrogel is formed. FIG. 16 is a phase transition of hydrogel formed when the concentration of Hy solution is 5mg/mL, the concentration of CA solution is 20mg/mL, and the mass ratio of CMCS to SA is different, the volume ratio of CA solution to Hy solution being different; FIG. 17 is a phase transition of hydrogel formed when the concentration of Hy solution is 10mg/mL, the concentration of CA solution is 10mg/mL, and the mass ratio of CMCS to SA is different, the volume ratio of CA solution to Hy solution being different; FIG. 18 is a phase transition of a hydrogel formed when the concentration of the Hy solution is 5mg/mL, the concentration of the CA solution is 10mg/mL, and the mass ratio of CMCS to SA is different from that of the Hy solution.

After the exploration and exploration of various test methods, the CMCS: SA is 1: 1(m/m) and the volume ratio V of the CA solution to the Hy solution_CA：V_HyIs that 2:1, it forms hydrogel with hymexazol very easily (see fig. 15-18 in particular). Hy solutions at low concentrations, do not readily form hydrogels with CA solutions (see fig. 16 and 18 in particular); with the increase of the concentration of the Hy solution, when the concentration of the CA solution is 2mg/mL and 5mg/mL, the CA solution and the Hy solution with the concentration of 1-10 mg/mL can form a flowable hydrogel; when the CA concentration was increased, hydrogels could be formed only in high concentration of hymexazol aqueous solution, and all gels were non-flowable hydrogels.

2.3 stability of active ingredients in hydrogels

This example uses HYG_A1And HYG_B1Detection of HYG as the subject of investigation_A1And HYG_B1The content of hymexazol as the effective component. HYG before and after gelling_A1And HYG_B1The detected amount of hymexazol is shown in fig. 19. As can be seen from the figure, the hydrogel formed under the condition of CA solution with high mass concentration (20mg/mL) or low mass concentration (10mg/mL) is equivalent to hymexazol solution with the same amount, and the ratio of the detected amount is about 100%. It was thus demonstrated that hymexazol is stably present in the hydrogel, and that hymexazol can be used as a carrier material and can still exert its pharmacological effect as an active ingredient.

2.4 hydrogel swelling Properties

FIGS. 20 and 21 are different Hydrogels (HYG) in 0.01M PBS and 0.1M PBS salt solutions at different pH's, respectively_A1、HYG_A2、HYG_B1And HYG_B2) The maximum swelling ratio of (a). Since the hydrogel has a three-dimensional network structure, it can absorb water in a salt solution to swell. The swelling performance of the hydrogel is different under different proportions, and the pH and the ion concentration of the solution also influence the swelling performance of the gel.

From FIG. 20 and the drawings21 it can be seen that the swelling of the hydrogel exhibits both pH and ion sensitivity. Hydrogel HYG formed when the concentration of CA solution is 10mg/mL in solutions with different ion concentrations_B1And HYG_B2The hydrogel has better swelling performance in different pH solutions, wherein the swelling ratio of the hydrogel in a concentration of 0.01M is more obvious, and the maximum swelling ratio is reached. The water soluble polymer can be dissolved quickly in ionic solution with high pH and high concentration, and the swelling ratio of the water soluble polymer cannot be detected. In a high-concentration ionic solution, the swelling of the hydrogel is increased along with the increase of pH, and the hydrogels with different proportions show the same swelling trend. When the ion concentration of the solution is reduced, the hydrogel slowly swells and erodes simultaneously; the swelling ratio obtained in the test is the combined result of erosion and swelling of the hydrogel.

2.5 biological Activity of hydrogels

Hydrogel HYG_B1The antagonism against sclerotinia sclerotiorum is shown in fig. 22. The hydrogel shows different bacteriostatic effects on pathogenic bacteria before and after drying. Hymexazol is more sensitive to sclerotinia sclerotiorum pathogenic bacteria, when using hydrogel HYG_B1After the treatment of the dishes, the pathogenic bacteria hardly grew (see B1, B2, C1 and C2 in fig. 22). The group A shows that the carrier material CA solution shows a certain bacteriostasis effect on the pathogenic bacteria of the sclerotinia rot of rape, but the width of the bacteriostasis band is not as obvious as that of the group B and the group C. Hydrogel HYG undried from heel group C_B1Compared with the treatment method, the hydrogel dried in the group B still has good bacteriostatic effect.

2.6 soil leaching Performance of the hydrogel

Granules GR and hydrogel HYG_A1The results of the soil leaching performance test are shown in FIG. 23, and it can be seen that the hydrogel HYG is obtained under the same volume of eluent_A1The total leaching amount (72.19%) of hymexazol is obviously lower than that of hymexazol granule (89.57%). Illustrative of the hydrogel HYG prepared in this example_A1The hymexazol as the medium-effective component has better combination effect with the carrier material, and has better soil leaching resistance compared with the hymexazol particles sold in the market.

2.7 hydrogel interfacial flow Rate

Through rain simulationAfter washing, the washing experiment results of the hydrogel and the commercial hymexazol water aqua (TJX) on the surfaces of the PTFE hydrophobic membrane and the cucumber leaf are shown in fig. 25 and 26; FIG. 24 is hydrogel HYG_C3And the flushing result of hymexazol water aqua (TJX) on the surfaces of the PTFE hydrophobic membrane and the cucumber leaf; as can be seen from the figure, no matter on the hydrophobic membrane or on the hydrophilic cucumber leaf, the hymexazol agent can be completely washed away, the washing rate is 100 percent, and the hydrogel HYG_C3The washing amount of the hymexazol is obviously different from the loss of the hymexazol in the hymexazol water aqua (TJX), and the loss amounts of the hymexazol in cucumber leaves and a hydrophobic film after gelation are respectively 43 percent and 54 percent.

The cucumber leaves have hydrophilicity, and can be fully contacted with the cucumber leaves when being washed by rainwater to wash away the hymexazol on the leaves, and the gelatinized hymexazol can be attached to a target interface. As shown in FIG. 25, hymexazol hydrogel HYG when simulating rainwash_C3And a protective film is formed on the hydrophobic film, so that hymexazol is adhered to the interface to reduce the chance of being washed by rainwater.

2.8 hydrogel bouncing Properties

The dynamic process of the droplets of the different treatment groups hitting the PTFE hydrophobic membrane is shown in fig. 27. When the pure water droplet hits the hydrophobic surface of PTFE, spreading and retraction to full bounce behavior occurs within 15ms (see FIG. 27-A panel). Although sodium alginate SA and carboxymethyl chitosan CMCS act as surfactants, they do not inhibit the bouncing of droplets, which still occur after the droplets land on the hydrophobic membrane and begin to bounce at 12ms (see FIG. 27-B). Commercial hymexazol aqua (see fig. 27-C group) and hymexazol aqueous solution (see fig. 27-D group) completed spreading, retracting, and fully bouncing behavior of the droplets within 15 ms. Due to the fact that the auxiliary agent is added into the commercial hymexazol water aqua, compared with the impact of hymexazol water aqua liquid drops, the hymexazol water solution is easy to crack and bounce when impacting the PTFE hydrophobic surface.

Gelation can obviously improve the phenomena of breakage and rebound of liquid drops on the hydrophobic surface of PTFE. According to the dynamic process result of hydrogel droplet impact, the hymexazol is not easy to bounce after gelation, the three-dimensional network structure between gels enables the gels to keep the appearance of the droplets without fragmentation and splashing, and the droplets can keep the lower parts of the droplets adhered to the solid surface in the 12ms rebound stage and cannot be completely bounced. The impact process of the hydrogels prepared under different mixture ratios is different (see fig. 27-E, F and G), the hydrogel formed by the high-concentration CA solution and the hymexazol can be more adhered to the hydrophobic surface, while the hydrogel formed by the low-concentration CA solution and the hymexazol has a bouncing tendency and is obviously bounced at 18 ms.

It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications are possible which remain within the scope of the appended claims.

Claims

1. The preparation method of the gel drug-loading system with pesticide molecule hymexazol as the gelatinizer is characterized by comprising the following steps:

step A: placing carboxymethyl chitosan CMCS and sodium alginate SA in the same container, adding water, and stirring until completely dissolving to obtain a mixed solution CA; the mass ratio of the carboxymethyl chitosan CMCS to the sodium alginate SA is 9: 1-1: 9; the mass concentration of the mixed solution CA is 2-20 mg/mL;

and B: dissolving hymexazol in solvent to prepare hymexazol solution Hy; preparing the hymexazol solution Hy by using water, methanol or ethanol as a solvent; the mass concentration of the hymexazol solution Hy is 0.5-10 mg/mL; the purity of the hymexazol is more than or equal to 98 wt%;

and C: mixing the mixed solution CA and the hymexazol solution Hy, and uniformly stirring to obtain a gel drug-loading system; the volume ratio of the mixed solution CA to the hymexazol solution Hy is 1: 2-8: 1.

2. The method for preparing a gel drug-loaded system with hymexazol as a gelling agent as a pesticide according to claim 1, wherein in step a, the carboxymethyl chitosan CMCS is O-carboxymethyl chitosan; the relative molecular mass of the carboxymethyl chitosan CMCS is 10-20 ten thousand.

3. The method for preparing the gel drug-loaded system with hymexazol as a gelling agent as the pesticide of claim 1, wherein in the step a, the purity of the sodium alginate SA is greater than or equal to 99 wt%.

4. The preparation method of the gel drug loading system with pesticide molecule hymexazol as a gelling agent according to claim 1, characterized in that the mass ratio of the carboxymethyl chitosan CMCS to the sodium alginate SA is 1:1, the concentration of the mixed solution CA is 20mg/mL, the concentration of the hymexazol solution Hy is 10mg/mL, and the volume ratio of the mixed solution CA to the hymexazol solution Hy is 2: 1.

5. The method for preparing a gel drug delivery system with hymexazol as a gelling agent as a pesticidal molecule according to any one of claims 1 to 4, wherein in step B, a pesticide soluble in the solvent is added to hymexazol solution Hy.

6. The method for preparing the gel drug-loaded system with hymexazol as the gelling agent as the pesticide of claim 5, wherein in the step B, the pesticide is: one or two or more of mixed aqueous solution or alcoholic solution of dicamba, glyphosate, glufosinate and imidacloprid, or one or two or more of alcoholic solution of 2,4-D, pyrithiobac-sodium, nitenpyram, indoxacarb, tricyclazole, propiconazole, epoxiconazole, fludioxonil, azoxystrobin, pyraclostrobin, tebuconazole, thifluzamide, difenoconazole, prothioconazole or prochloraz; the alcohol solution is a methanol solution or an ethanol solution.

7. Use of the pesticidal molecule hymexazol as a gel drug carrier of a gelling agent, characterized in that the gel drug carrier prepared according to claims 1 to 6 is used for loading a pesticidal active ingredient.