Application of cyclodextrin loaded salicylic acid alkaloid eutectic crystal

Abstract

The invention relates to the field of pesticides, and discloses an application of a cyclodextrin-loaded salicylic acid alkaloid eutectic crystal, including an application of the cyclodextrin-loaded salicylic acid alkaloid eutectic crystal as a safener in reduction of poison of a herbicide to crops and an application of the cyclodextrin-loaded salicylic acid alkaloid eutectic crystal in preparation of a weeding composition. The cyclodextrin-loaded salicylic acid alkaloid eutectic can effectively reduce the poison of a herbicide to the growth of crops.

Description

Technical Field

[0001] The present invention relates to the field of pesticides, and in particular to an application of a cyclodextrin-loaded salicylic acid alkaloid cocrystal, including an application of the cyclodextrin-loaded salicylic acid alkaloid cocrystal as a safener in reducing the toxicity of herbicides to crops, and an application of the cyclodextrin-loaded salicylic acid alkaloid cocrystal in preparing a herbicidal composition. Background Art

[0002] Weed damage is one of the three major biological disasters in agricultural production. There are many types of weeds and they are very harmful. Every year, they cause a large loss of world grain production and huge economic losses. With the continuous development of agricultural technology, herbicides have become an indispensable part of modern agriculture. They are mainly used to control weeds in the field, reduce labor intensity, and improve the yield and quality of crops. However, the application of herbicides in crops will have a negative impact on crops, such as pesticide damage, residues, etc., which will have an adverse effect on the growth and yield of crops. In severe cases, it may even lead to crop failure. The use of herbicide safeners is the most direct and effective way to solve the problem of herbicide damage.

[0003] Herbicide safeners, also known as antidotes or protectants, are a class of compounds that can protect crops from herbicide damage. They improve weed control by increasing crop resistance and improving the selectivity of herbicides. However, the ability of herbicide safeners to mitigate the toxicity of herbicides to crop growth needs to be improved. For example, the herbicide safener fenthiocarb, which is commonly used in rice fields, has the limitation of poor solubility during use, and its effective utilization rate is low.

[0004] Therefore, there is an urgent need to provide a herbicide safener that can effectively alleviate the toxicity of herbicides to crop growth. Summary of the invention

[0005] The purpose of the present invention is to overcome the problem that the herbicide safener in the prior art cannot effectively reduce the toxicity of the herbicide to the growth of crops, and to provide an application of a cyclodextrin-loaded salicylic acid alkaloid cocrystal, including the application of the cyclodextrin-loaded salicylic acid alkaloid cocrystal as a safener in reducing the toxicity of herbicides to crops and the application of the cyclodextrin-loaded salicylic acid alkaloid cocrystal in preparing a herbicidal composition. The cyclodextrin-loaded salicylic acid alkaloid cocrystal has good solubility and can effectively reduce the toxicity of the herbicide to the growth of crops.

[0006] The first aspect of the present invention provides the use of cyclodextrin-loaded salicylic acid alkaloid co-crystal as a safener in reducing the toxicity of herbicides to crops.

[0007] Preferably, the alkaloid is selected from at least one of matrine, betaine, theophylline, tetrahydropalmatine and choline, and more preferably matrine.

[0008] Preferably, the herbicide is selected from at least one of S-metolachlor, acetochlor, thiamethoxam, nicosulfuron, sulfamethoxam and fenoxaprop-butyl, and more preferably S-metolachlor.

[0009] Preferably, the crop is selected from at least one of rice, wheat, barley, corn, sorghum, cotton, soybean, peanut and rapeseed, and more preferably rice.

[0010] The second aspect of the present invention provides the use of cyclodextrin-loaded salicylic acid alkaloid co-crystal in the preparation of a herbicidal composition.

[0011] Preferably, the preparation process of the cyclodextrin-loaded salicylic acid alkaloid cocrystal comprises the following steps:

[0012] (1) in the presence of solvent I, 3-nitrosalicylic acid and alkaloids are mixed to react I, and salicylic acid alkaloid cocrystals are obtained by separation;

[0013] (2) In the presence of solvent II, cyclodextrin and the salicylic acid alkaloid cocrystal are subjected to a mixing reaction II.

[0014] Preferably, in step (1), the solvent I is selected from at least one of methanol, ethanol and acetone, more preferably methanol and / or ethanol.

[0015] Preferably, the weight ratio of the 3-nitrosalicylic acid to the alkaloid is 1:1-2.

[0016] Preferably, the conditions of the mixing reaction I at least include: a temperature of 50-70° C., a time of 10-60 min, and a rotation speed of 200-400 rpm.

[0017] Preferably, in step (2), the solvent II is methanol and / or ethanol, more preferably ethanol.

[0018] Preferably, the cyclodextrin is hydroxypropyl-β-cyclodextrin.

[0019] Preferably, the weight ratio of the cyclodextrin to the salicylic acid alkaloid co-crystal is 2-5:1.

[0020] Preferably, the conditions of the mixed reaction II at least include: temperature of 30-40°C, time of 4-6h, and rotation speed of 200-400rpm.

[0021] Through the above technical scheme, the beneficial effects of the present invention are as follows: the cyclodextrin-loaded salicylic acid alkaloid cocrystal provided by the present invention has good solubility and dissolution rate in water through the synergistic effect between the salicylic acid alkaloid cocrystal and cyclodextrin, and can be used as a safener to significantly alleviate the toxicity of herbicides to the growth of crops. Moreover, the use of the cyclodextrin-loaded salicylic acid alkaloid cocrystal in the preparation of a herbicidal composition can promote the growth of crops, thereby increasing the yield of crops, and has significant economic benefits.

[0022] Other features and advantages of the present invention will be described in detail in the following detailed description. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is the infrared spectrum of the cyclodextrin-loaded matrine salicylate co-crystal prepared in Example 1. DETAILED DESCRIPTION

[0024] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0025] The first aspect of the present invention provides the use of cyclodextrin-loaded salicylic acid alkaloid co-crystal as a safener in reducing the toxicity of herbicides to crops.

[0026] The present invention provides a new use of cyclodextrin-loaded salicylic acid alkaloid cocrystals, and the inventors have found through research that the salicylic acid alkaloid cocrystals can reduce the toxicity of herbicides to crops; through the synergistic effect between the salicylic acid alkaloid cocrystals and cyclodextrin, the cyclodextrin-loaded salicylic acid alkaloid cocrystals have good solubility and dissolution rate in water, and the ability of the cyclodextrin-loaded salicylic acid alkaloid cocrystals to reduce the toxicity of herbicides to crops is further improved, and the cyclodextrin-loaded salicylic acid alkaloid cocrystals can be used as a safener to reduce the toxicity of herbicides to crops, which has significant economic benefits.

[0027] According to the present invention, the alkaloid is an alkaloid that can form a cocrystal with 3-nitrosalicylic acid. In order to enable the salicylic acid alkaloid cocrystal to further reduce the toxicity of the herbicide to the growth of crops, preferably, the alkaloid is selected from at least one of matrine, betaine, theophylline, tetrahydropalmatine and choline, and matrine is further preferred.

[0028] According to the present invention, the herbicide can be a herbicide conventionally selected by technicians in the field for crop growth. Preferably, the herbicide is selected from at least one of S-isopropylamine, acetochlor, thiamethoxam, nicosulfuron, sulfamethoxam and fenoxaprop-butyl, and is further preferably S-isopropylamine.

[0029] According to the present invention, the crops can be food crops or cash crops. Preferably, the crops are selected from at least one of rice, wheat, barley, corn, sorghum, cotton, soybean, peanut and rapeseed, more preferably rice.

[0030] The second aspect of the present invention provides the use of cyclodextrin-loaded salicylic acid alkaloid co-crystal in the preparation of a herbicidal composition.

[0031] The present invention provides another new use for cyclodextrin-loaded salicylic acid alkaloid co-crystals, and the inventors have found that the cyclodextrin-loaded salicylic acid alkaloid co-crystals are used to prepare a herbicidal composition, which can reduce the toxicity of the herbicidal composition to crops while removing weeds.

[0032] In the present invention, the herbicidal composition contains cyclodextrin-loaded salicylic acid alkaloid cocrystal and a herbicide. The cyclodextrin-loaded salicylic acid alkaloid cocrystal and the herbicide can be mixed in any proportion. Preferably, the weight ratio of the cyclodextrin-loaded salicylic acid alkaloid cocrystal to the herbicide is 100-200:1, specifically 100:1, 150:1, 200:1, or any value between the foregoing two values.

[0033] In the present invention, the herbicidal composition further contains a solvent, and the solvent may be water, N,N-dimethylformamide or dimethyl sulfoxide. The concentration of the cyclodextrin-loaded salicylic acid alkaloid cocrystal in the herbicidal composition is not particularly limited. Preferably, the concentration of the cyclodextrin-loaded salicylic acid alkaloid cocrystal is 5-10 mg / L, specifically 5 mg / L, 6 mg / L, 7 mg / L, 8 mg / L, 9 mg / L, 10 mg / L, or any value between the above two values.

[0034] In the present invention, the cyclodextrin-loaded salicylic acid alkaloid co-crystal can be purchased commercially or prepared by itself. Preferably, the preparation process of the cyclodextrin-loaded salicylic acid alkaloid co-crystal comprises the following steps:

[0035] (1) in the presence of solvent I, 3-nitrosalicylic acid and alkaloids are mixed to react I, and salicylic acid alkaloid cocrystals are obtained by separation;

[0036] (2) In the presence of solvent II, cyclodextrin and the salicylic acid alkaloid cocrystal are subjected to a mixing reaction II.

[0037] According to the present invention, in step (1), solvent I is an organic solvent capable of dissolving 3-nitrosalicylic acid and alkaloids. In order to further improve the reaction effect of salicylic acid alkaloid eutectic, preferably, the solvent I is selected from at least one of methanol, ethanol and acetone, more preferably methanol and / or ethanol, and solvent I can be methanol, ethanol, or methanol and ethanol. Exemplarily, 3-nitrosalicylic acid is dissolved in a mixed solution of ethanol and methanol, and matrine is dissolved in ethanol. The amount of solvent I is not particularly limited, and it can have the effect of dissolving 3-nitrosalicylic acid and alkaloids. The inventors found that under this preferred embodiment, the prepared salicylic acid alkaloid eutectic has the ability to reduce the toxicity of herbicides to crop growth.

[0038] In the present invention, the alkaloid is an alkaloid that can form a cocrystal with 3-nitrosalicylic acid. In order to enable the salicylic acid alkaloid cocrystal to further reduce the toxicity of the herbicide to the growth of crops, preferably, the alkaloid is selected from at least one of matrine, betaine, theophylline, tetrahydropalmatine and choline, and matrine is more preferably used.

[0039] According to the present invention, 3-nitrosalicylic acid and alkaloids can be mixed in any proportion. In order to further improve the reaction effect of salicylic acid alkaloid cocrystal, preferably, the weight ratio of the 3-nitrosalicylic acid to the alkaloid is 1:1-2, specifically 1:1, 1:1.5, 1:2, or any value between the foregoing two values.

[0040] According to the present invention, in order to further improve the reaction effect of salicylic acid alkaloid cocrystal, preferably, the conditions of the mixed reaction I at least include: a temperature of 50-70°C, specifically 50°C, 60°C, 70°C, or any value between the foregoing two values; a time of 10-60min, specifically 10min, 20min, 30min, 40min, 50min, 60min, or any value between the foregoing two values; a rotation speed of 200-400rpm, specifically 200rpm, 300rpm, 400rpm, or any value between the foregoing two values.

[0041] In the present invention, separation can be performed by a separation method conventionally selected in the art, such as centrifugation, filtration or suction filtration.

[0042] According to the present invention, in step (2), solvent II is an organic solvent capable of dissolving salicylic acid alkaloid eutectic. In order to further improve the reaction effect of cyclodextrin-loaded salicylic acid alkaloid eutectic, preferably, the solvent II is methanol and / or ethanol, and solvent II can be methanol, ethanol, or methanol and ethanol. Further preferably, solvent II is ethanol. The inventors found that under this preferred embodiment, through the synergistic effect of cyclodextrin and salicylic acid alkaloid eutectic, cyclodextrin-loaded salicylic acid alkaloid eutectic has good solubility and dissolution rate in water, and using it as a safener can significantly reduce the toxicity of herbicides to crop growth.

[0043] In the present invention, cyclodextrin is a general term for a series of cyclic oligosaccharides generated by amylose under the action of cyclodextrin glucosyltransferase produced by Bacillus, and generally contains 6-12 D-pyranose units. In order to further improve the reaction effect of cyclodextrin-loaded salicylic acid alkaloid cocrystal, preferably, the cyclodextrin is hydroxypropyl-β-cyclodextrin.

[0044] In the present invention, there is no particular limitation on the molecular weight of cyclodextrin. In order to further enhance the effect of cyclodextrin-loaded salicylic acid alkaloid cocrystal in reducing the toxicity of herbicides to crops, preferably, the molecular weight of cyclodextrin is 600-3000Da, which can be purchased commercially.

[0045] According to the present invention, cyclodextrin and salicylic acid alkaloid cocrystals can be mixed in any proportion. In order to further improve the reaction effect of cyclodextrin-loaded salicylic acid alkaloid cocrystals, preferably, the weight ratio of the cyclodextrin to the salicylic acid alkaloid cocrystal is 2-5:1, specifically 2:1, 3:1, 4:1, 5:1, or any value between the foregoing two values.

[0046] According to the present invention, in order to further improve the reaction effect of cyclodextrin-loaded salicylic acid alkaloid cocrystal, preferably, the conditions of the mixed reaction II at least include: the temperature is 30-40°C, specifically 30°C, 35°C, 40°C, or any value between the foregoing two values; the time is 4-6h, specifically 4h, 5h, 6h, or any value between the foregoing two values; the rotation speed is 200-400rpm, specifically 200rpm, 300rpm, 400rpm, or any value between the foregoing two values.

[0047] The present invention will be described in detail below through examples.

[0048] In the following examples, 3-nitrosalicylic acid was purchased from Jilin Zhongke Shen Technology Co., Ltd. with a purity of 98%; matrine was purchased from Jilin Zhongke Shen Technology Co., Ltd. with a purity of 98%; hydroxypropyl-β-cyclodextrin was purchased from Jilin Zhongke Shen Technology Co., Ltd. with a purity of 98%; unless otherwise specified, the remaining raw materials or reagents are conventional commercially available products.

[0049] Example 1

[0050] (1) 6 ml of anhydrous ethanol and 2 ml of methanol were added to 0.5 g of 3-nitrosalicylic acid to obtain a 3-nitrosalicylic acid solution, 2 ml of anhydrous ethanol was added to 0.69 g of matrine to obtain a matrine solution, the 3-nitrosalicylic acid solution and the matrine solution were added dropwise and mixed, and stirred at 60° C. and 300 rpm for 30 min. A yellow solid was produced in the mixed solution, and the mixed solution was filtered to obtain salicylic acid matrine cocrystals. The yield of salicylic acid matrine cocrystals was 99.0%;

[0051] (2) 1.08 g of matrine salicylate cocrystal and 3.75 g of hydroxypropyl-β-cyclodextrin were added to 30 ml of ethanol to obtain a mixed solution, which was stirred at 35° C. and 300 rpm for 5 h. The mixed solution was then rotary evaporated to dryness at 45° C. to obtain cyclodextrin-loaded matrine salicylate cocrystal. The drug loading rate of cyclodextrin on matrine salicylate cocrystal was 85%;

[0052] (3) Dissolving cyclodextrin-loaded matrine salicylate cocrystal and S-metolachlor in water so that the concentration of cyclodextrin-loaded matrine salicylate cocrystal is 8 mg / L and the concentration of S-metolachlor is 0.25 μmol / L, to obtain a herbicidal composition.

[0053] The infrared spectrum of the cyclodextrin-loaded salicylic acid matrine co-crystal prepared in Example 1 is shown in Figure 1 .

[0054] Example 2

[0055] (1) 6 ml of anhydrous ethanol and 2 ml of methanol were added to 0.5 g of 3-nitrosalicylic acid to obtain a 3-nitrosalicylic acid solution, 2 ml of anhydrous ethanol was added to 0.5 g of matrine to obtain a matrine solution, the 3-nitrosalicylic acid solution and the matrine solution were added dropwise and mixed, and stirred at 50° C. and 400 rpm for 60 min. A yellow solid was produced in the mixed solution, and the mixed solution was filtered to obtain salicylic acid matrine cocrystals. The yield of salicylic acid matrine cocrystals was 63%;

[0056] (2) 0.78 g of matrine salicylate cocrystal and 1.56 g of hydroxypropyl-β-cyclodextrin were added to 30 ml of ethanol to obtain a mixed solution, which was stirred at 30° C. and 200 rpm for 4 h, and then the mixed solution was rotary evaporated to dryness at 45° C. to obtain cyclodextrin-loaded matrine salicylate cocrystal, and the drug loading rate of cyclodextrin on matrine salicylate cocrystal was 80%;

[0057] (3) Dissolving cyclodextrin-loaded matrine salicylate cocrystal and S-metolachlor in water so that the concentration of cyclodextrin-loaded matrine salicylate cocrystal is 5 mg / L and the concentration of S-metolachlor is 0.1 μmol / L, to obtain a herbicidal composition.

[0058] Example 3

[0059] (1) 6 ml of anhydrous ethanol and 2 ml of methanol were added to 0.5 g of 3-nitrosalicylic acid to obtain a 3-nitrosalicylic acid solution, 2 ml of anhydrous ethanol was added to 1.0 g of matrine to obtain a matrine solution, the 3-nitrosalicylic acid solution and the matrine solution were added dropwise and mixed, and stirred at 70° C. and 200 rpm for 10 min. A yellow solid was produced in the mixed solution, and the mixed solution was filtered to obtain salicylic acid matrine cocrystals. The yield of salicylic acid matrine cocrystals was 70%;

[0060] (2) 1.25 g of matrine salicylate cocrystal and 6.25 g of hydroxypropyl-β-cyclodextrin were added to 30 ml of ethanol to obtain a mixed solution, which was stirred at 40° C. and 400 rpm for 6 h, and then the mixed solution was rotary evaporated to dryness at 45° C. to obtain cyclodextrin-loaded matrine salicylate cocrystal, and the drug loading rate of cyclodextrin on matrine salicylate cocrystal was 75%;

[0061] (3) Dissolving cyclodextrin-loaded matrine salicylate cocrystal and S-metolachlor in water so that the concentration of cyclodextrin-loaded matrine salicylate cocrystal is 10 mg / L and the concentration of S-metolachlor is 0.18 μmol / L, thereby obtaining a herbicidal composition.

[0062] Example 4

[0063] (1) 1.08 g of betaine salicylate cocrystal and 3.75 g of hydroxypropyl-β-cyclodextrin were added to 30 ml of ethanol to obtain a mixed solution, which was stirred at 35° C. and 300 rpm for 5 h, and then the mixed solution was rotary evaporated to dryness at 45° C. to obtain cyclodextrin-loaded betaine salicylate cocrystal, and the drug loading rate of cyclodextrin on betaine salicylate cocrystal was 82%;

[0064] (2) Dissolving cyclodextrin-loaded betaine salicylate cocrystal and S-metolachlor in water so that the concentration of cyclodextrin-loaded matrine salicylate cocrystal is 8 mg / L and the concentration of S-metolachlor is 0.25 μmol / L, thereby obtaining a herbicidal composition.

[0065] Example 5

[0066] A herbicidal composition was prepared according to the method of Example 1, except that S-metolachlor in step (3) was replaced by acetochlor.

[0067] Comparative Example 1

[0068] The herbicidal composition was prepared according to the method of Example 1, except that step (2) and step (3) were replaced by:

[0069] (2) Dissolving matrine salicylate cocrystal and S-metolachlor in water so that the concentration of matrine salicylate cocrystal is 8 mg / L and the concentration of S-metolachlor is 0.25 μmol / L, to obtain a herbicidal composition.

[0070] Comparative Example 2

[0071] Fenclorac and S-metolachlor were dissolved in water so that the concentration of fenclorac was 8 mg / L and the concentration of S-metolachlor was 0.25 μmol / L, to obtain a herbicidal composition.

[0072] Comparative Example 3

[0073] The herbicidal composition was prepared according to the method of Example 1, except that step (2) and step (3) were replaced by:

[0074] (2) Dissolving matrine salicylate cocrystal, hydroxypropyl-β-cyclodextrin and S-isopropylamine in water so that the concentration of cyclodextrin-loaded matrine salicylate cocrystal is 2 mg / L, the concentration of hydroxypropyl-β-cyclodextrin is 6 mg / L, and the concentration of S-isopropylamine is 0.25 μmol / L, to obtain a herbicidal composition.

[0075] Test Case

[0076] The rice seeds were disinfected with 0.1wt% hypochlorous acid and then rinsed with deionized water for 3 times, then soaked in deionized water at 28°C for 24h, and then germinated in the dark for 36h. Before the embryo germination, the rice seedlings with consistent radicle germination were selected and transplanted into small round transparent plastic boxes containing agar culture medium (specifications: outer diameter 14cm, inner diameter 12.5cm, height 9cm, round, volume 916mL), and then transferred to a light incubator for cultivation. First, the light was illuminated for 14h (light intensity 110-130μE·m -2 s -1 , temperature was 30°C), followed by incubation at 25°C in the dark for 10 h;

[0077] Select rice seedlings with consistent shoot length and root length, and evenly distribute the rice seedlings on the surface of agar medium containing the herbicidal compositions obtained in Examples 1 to 5 and Comparative Examples 1 to 2, respectively, and set them as Example 1 group, Example 2 group, Example 3 group, Example 4 group, Example 5 group, Comparative Example 1 group, Comparative Example 2 group, and Comparative Example 3 group; select rice seedlings with consistent shoot length and root length, and evenly distribute the rice seedlings on the surface of agar medium containing an aqueous solution of S-isopropylamine with a concentration of 0.25 μmol / L, and set them as a control group; select rice seedlings with consistent shoot length and root length, and evenly distribute the rice seedlings on the surface of agar medium containing only water, and set them as a blank group;

[0078] The Example 1 to Example 5 groups, the Comparative Example 1 to Comparative Example 3 groups, the control group and the blank group were transferred into a light incubator for culture. The light was controlled to be: 14 h (light intensity 110-130 μE·m -2 s -1 , temperature 30℃, time 6:00-20:00), dark 10h (temperature 25℃, time 20:00-6:00). Maintain appropriate humidity in the first few days, and increase watering (watering time 8:00) after the rice grows to the three-leaf stage. Measure the root length of rice half a month later. The results are shown in Table 1.

[0079] Table 1

[0080]

[0081]

[0082] It can be seen from the results in Table 1 that, compared with Comparative Example 1 to Comparative Example 3, the herbicidal compositions prepared by Example 1 to Example 5 using the cyclodextrin-loaded salicylic acid alkaloid cocrystal provided by the present invention significantly reduced the toxicity of the herbicide to rice.

[0083] The preferred embodiments of the present invention are described in detail above, but the present invention is not limited thereto. Within the technical concept of the present invention, the technical solution of the present invention can be subjected to a variety of simple modifications, including the combination of various technical features in any other suitable manner, and these simple modifications and combinations should also be regarded as the contents disclosed by the present invention and belong to the protection scope of the present invention.

Claims

1. Application of cyclodextrin-loaded salicylic acid alkaloid cocrystals as safeners in reducing the toxicity of herbicides to crops.

2. The use according to claim 1, characterized in that: The alkaloid is at least one selected from matrine, betaine, theophylline, tetrahydropalmatine and choline, preferably matrine.

3. The use according to claim 1, characterized in that: The herbicide is at least one selected from the group consisting of S-metolachlor, acetochlor, thiamethoxam, nicosulfuron, sulfamethoxam and fenoxaprop-butyl, preferably S-metolachlor.

4. The use according to claim 1, characterized in that: The crop is selected from at least one of rice, wheat, barley, corn, sorghum, cotton, soybean, peanut and rapeseed, preferably rice.

5. Application of cyclodextrin-loaded salicylic acid alkaloid cocrystals in the preparation of herbicidal compositions.

6. The use according to any one of claims 1 to 5, characterized in that: The preparation process of the cyclodextrin-loaded salicylic acid alkaloid cocrystal comprises the following steps: (1) in the presence of solvent I, 3-nitrosalicylic acid and alkaloids are mixed to react I, and salicylic acid alkaloid cocrystals are obtained by separation; (2) In the presence of solvent II, cyclodextrin and the salicylic acid alkaloid cocrystal are subjected to a mixing reaction II.

7. The use according to claim 6, characterized in that: In step (1), the solvent I is selected from at least one of methanol, ethanol and acetone, preferably methanol and / or ethanol.

8. The use according to claim 7, characterized in that: The weight ratio of the 3-nitrosalicylic acid to the alkaloid is 1:1-2; Preferably, the conditions of the mixing reaction I at least include: a temperature of 50-70° C., a time of 10-60 min, and a rotation speed of 200-400 rpm.

9. The use according to claim 6, characterized in that: In step (2), the solvent II is methanol and / or ethanol, preferably ethanol; Preferably, the cyclodextrin is hydroxypropyl-β-cyclodextrin.

10. The use according to claim 9, characterized in that: The weight ratio of the cyclodextrin to the salicylic acid alkaloid cocrystal is 2-5:1; Preferably, the conditions of the mixed reaction II at least include: temperature of 30-40°C, time of 4-6h, and rotation speed of 200-400rpm.

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