Celangulin V solid dispersion, its preparation method and application

Abstract

The present invention relates to the field of plant pesticides and preparations, and specifically discloses a celangulin V solid dispersion, its preparation method and application. The celangulin V solid dispersion is composed of celangulin V and a hydrophilic carrier. Among them, the proportion of celangulin V is 9.1% - 33.3%, and the proportion of the hydrophilic carrier is 66.7% - 90.9%. The celangulin V solid dispersion is prepared by a melting method or a solvent method. The hydrophilic carrier includes 2-hydroxypropyl-β-cyclodextrin, PEG 4000, chitosan, PEG 6000, mannitol or PVP K30. The present invention prepares the poorly soluble drug celangulin V into a solid dispersion, effectively improving the solubility and dissolution rate of celangulin V, ensuring good physical stability while maintaining a highly dispersed state and having good insecticidal activity.

Description

Technical Field

[0001] The present invention relates to the field of plant pesticides and preparations, and specifically discloses a celangulin V solid dispersion, a preparation method thereof, and an application thereof. Background Art

[0002] Celangulin V: Chemical name: (3R,4S,5R,5aR,6R,7S,9s,9aS,10R)-5-(benzoyloxy)-9,10-dihydroxy-5a-(isobutoxymethyl)-4-isobutyryl-2,2,9-trimethyloctahydro-2H-3,9a-methanobenzo[b]oxepine-6,7-diyl diacetate, molecular formula: C 34 H 48 O 11 , molecular weight: 632, and the structure is shown as follows:

[0003]

[0004] Celangulin V is an insecticidal active ingredient extracted from the root bark of Celasturs angulatus Maxim, a widely distributed insecticidal plant. It has good insecticidal and antibacterial effects and is an excellent plant-derived pesticide. Celangulin is also a new type of grain protectant used for the control of stored grain pests and has broad development space and application prospects.

[0005] Celangulin V is a new type of plant-derived insecticidal active substance invented by the laboratory of Professor Wu Wenjun at Northwest A&F University. Wu Wenjun et al. have shown that celangulin V can damage the midgut wall cells of insects, causing insects to vomit and diarrhea, and die due to excessive water loss. Lu Lina et al. have pointed out the mechanism of action of celangulin V: The plant insecticide mainly composed of celangulin V is sprayed and deposited on the leaves of crops. The drug is ingested into the digestive tract with the feeding activities of pests, penetrates the peritrophic membrane, enters the intestinal cavity, binds to the V-ATPase H subunit on the cytoplasmic membrane of the intestinal wall, hinders the assembly of the H subunit and other subunits into the V1 complex, and thus hinders the assembly of the V1 and V0 complexes into the V-ATPase holoenzyme on the apical membrane of goblet cells, inhibiting the activity of V-ATPase. This may be the reason for the loss of a large amount of body fluid (part of which is hemolymph) by insects and their ultimate death.

[0006] Compared with traditional pesticides, celangulin V has the characteristics of no drug resistance, no killing of natural enemies, and stable physical and chemical properties. However, celangulin V has poor water solubility, resulting in slow release rate, rapid metabolism, and low bioavailability, which limits the development and utilization of its preparations. Summary of the Invention

[0007] To solve the problems pointed out in the background art section, the present invention provides a celangulin V solid dispersion, its preparation method and application.

[0008] The celangulin V solid dispersion is composed of celangulin V and a hydrophilic carrier. Among them, the proportion of celangulin V is 9.1% - 33.3%, and the proportion of the hydrophilic carrier is 66.7% - 90.9%.

[0009] The above celangulin V solid dispersion is prepared according to the following steps:

[0010] 1) Grind and sieve the original celangulin V drug and the hydrophilic carrier separately.

[0011] 2) Weigh celangulin V and the hydrophilic carrier respectively according to the proportion that celangulin V accounts for 9.1% - 33.3% and the hydrophilic carrier accounts for 66.7% - 90.9%.

[0012] 3) Prepare the celangulin V solid dispersion by the melting method or the solvent method.

[0013] Among them, when preparing the celangulin V solid dispersion by the melting method, the hydrophilic carrier used is one of PEG4000, chitosan, and PEG6000.

[0014] The operation of the melting method is as follows:

[0015] Weigh celangulin V and the hydrophilic carrier respectively according to the proportion that celangulin V accounts for 9.1% - 33.3% and the hydrophilic carrier accounts for 66.7% - 90.9%. Add the hydrophilic carrier to the reaction vessel, stir and heat it to the molten state, add celangulin V in multiple batches and in small amounts. After adding, continue to react for 30 - 90 minutes. After the reaction is completed, quickly cool the reaction mixture to a solid under vigorous stirring, or pour the reaction mixture onto a stainless steel plate to form a thin layer, and quickly cool it to a solid with cold air or ice water. Then place this solid at a certain temperature until it becomes brittle and fragile, crush it and sieve it to obtain the celangulin V solid dispersion.

[0016] When preparing the celangulin V solid dispersion by the solvent method, the hydrophilic carrier used is one or more of 2 - hydroxypropyl - β - cyclodextrin, PEG6000, mannitol, and PVP K30.

[0017] The operation of the solvent method is as follows:

[0018] Weigh celangulin V and hydrophilic carrier respectively according to the proportion of celangulin V being 9.1% - 33.3% and the proportion of hydrophilic carrier being 66.7% - 90.9%. Dissolve celangulin V and hydrophilic carrier material together in an organic solvent, and ultrasonicate or heat until it is clear and transparent. After rotary evaporation to remove the organic solvent, the drug and the carrier material precipitate simultaneously. Dry, pulverize, and sieve it to obtain the celangulin V solid dispersion.

[0019] Among them, the organic solvent is ethanol, methanol, dichloromethane, ethyl acetate, toluene, acetone, and methanol is preferred.

[0020] Compared with the prior art, the features and beneficial effects of the present invention are as follows:

[0021] 1) For the celangulin V solid dispersion provided by the present invention, the use of a hydrophilic carrier increases the solubility and dissolution rate of the poorly soluble drug celangulin V, which helps to improve the bioavailability of the drug.

[0022] 2) For the celangulin V solid dispersion provided by the present invention, celangulin V can be uniformly dispersed in the carrier in a highly dispersed state such as molecular, amorphous, microcrystalline state, etc., and good physical stability is ensured while maintaining the highly dispersed state.

[0023] 3) Compared with traditional pesticides, the celangulin V solid dispersion provided by the present invention has the characteristics of not generating drug resistance, not killing natural enemies, and stable physical and chemical properties.

[0024] 4) For the preparation method of the celangulin V solid dispersion provided by the present invention, the process is simple and easy to operate, the raw materials are cheap and the cost is low, and it is easy to industrialize the production. Description of the Drawings

[0025] Figures 1 to 4 It is a comparative diagram of in vitro dissolution curves of celangulin V raw drug, some examples and solid dispersions obtained from comparative examples.

[0026] Figures 5 to 17 It is an FTIR analysis spectrum diagram of celangulin V raw drug, some examples and solid dispersions obtained from comparative examples.

[0027] Figure 18 It is an SEM scanning spectrum diagram of celangulin V raw drug, physical mixture, and celangulin V solid dispersion. Among them, A: celangulin V; B: physical mixture of celangulin V - PVP K30 - 2 - hydroxypropyl - β - cyclodextrin (1:3:7); C: solid dispersion obtained in Example 10. Detailed Embodiments

[0028] In order to more clearly illustrate the purpose, technical solution and advantages of the present invention, the present invention will be further described in detail below with reference to the drawings and specific examples.

[0029] In the embodiment of the present invention, the dissolution rate of celangulin V solid dispersion was determined by the paddle method according to the Chinese Pharmacopoeia (2015 Edition): the release medium was 0.02% SDS aqueous solution, the temperature was (37±0.5)°C, and the rotation speed was 100 r / min. Accurately weigh the physical mixture and solid dispersions in various proportions into a 250 ml dissolution cup, take 1 mL of sample at 5, 10, 20, 40, 60, 90, and 120 min, filter through a 0.22 μm microporous filter membrane, and supplement the release medium with the same temperature and volume at the same time. Using the release medium as the blank control, measure the absorbance value at 229 nm, calculate the cumulative dissolution rate at each time period, and draw the dissolution curve.

[0030] Example 1

[0031] The celangulin V solid dispersion was composed of celangulin V and PEG4000. By the melting method, 1000 mg of PEG4000 was heated to melting in a water bath at 65°C. Under continuous stirring, 100 mg of celangulin V was added in 5 portions, and stirring was continued for 30 min. The melt was poured onto a glass container to form a thin layer, quickly cooled, dried in a desiccator for 24 h, pulverized, and sieved through a 100-mesh sieve to obtain the celangulin V / PEG4000 solid dispersion. The results of in vitro dissolution experiments showed that the dissolution rate at 5 min was 46.20%, and the dissolution rate at 2 h was 63.02%. It can be seen that the solid dispersion prepared with PEG4000 as the carrier can effectively improve the dissolution behavior of celangulin V.

[0032] Comparative Example 1

[0033] The physical mixture of celangulin V was prepared by adding 1000 mg of PEG4000 and 100 mg of celangulin V into a mortar and grinding them thoroughly to make a homogeneous mixture, and then sieving through a 100-mesh sieve to obtain the celangulin V / PEG4000 physical mixture. The results of in vitro dissolution experiments showed that the dissolution rate at 5 min was 15.37%, and the dissolution rate at 2 h was 40.19%.

[0034] Example 2

[0035] The celangulin V solid dispersion was composed of celangulin V and PEG6000. By the melting method, 1000 mg of PEG6000 was heated to melting in a water bath at 70°C. Under continuous stirring, 100 mg of celangulin V was added in 5 portions, and stirring was continued for 30 min. The melt was poured onto a glass container to form a thin layer, quickly cooled, dried in a desiccator for 24 h, pulverized, and sieved through a 100-mesh sieve to obtain the celangulin V / PEG6000 solid dispersion. The results of in vitro dissolution experiments showed that the dissolution rate at 5 min was 51.06%, and the dissolution rate at 2 h was 60.48%. It can be seen that the solid dispersion prepared with PEG6000 as the carrier can effectively improve the dissolution behavior of celangulin V.

[0036] Example 3

[0037] Celangulin V solid dispersion, composed of celangulin V and PVP K30. Using the solvent method, 1000 mg of PVP K30 and 100 mg of celangulin V were dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, then the solvent was removed by rotary evaporation under reduced pressure. The obtained product was dried in a vacuum drying oven for 24 h, pulverized, and passed through a 100-mesh sieve to obtain the celangulin V / PVP K30 solid dispersion. The in vitro dissolution test results showed that the dissolution rate at 5 min was 54.58%, and the dissolution rate at 2 h was 62.45%. It can be seen that the solid dispersion prepared with PVP K30 as the carrier can effectively improve the dissolution behavior of celangulin V.

[0038] Comparative Example 2

[0039] Physical mixture of celangulin V. 1000 mg of PVP K30 and 100 mg of celangulin V were added to a mortar and ground thoroughly to make a homogeneous mixture, and then passed through a 100-mesh sieve to obtain the celangulin V / PVP K30 physical mixture. The in vitro dissolution test results showed that the dissolution rate at 5 min was 17.94%, and the dissolution rate at 2 h was 41.63%.

[0040] Example 4

[0041] Celangulin V solid dispersion, composed of celangulin V and PEG6000. Using the solvent method, 1000 mg of PEG6000 and 100 mg of celangulin V were dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, then the solvent was removed by rotary evaporation under reduced pressure. The obtained product was dried in a vacuum drying oven for 24 h, pulverized, and passed through a 100-mesh sieve to obtain the celangulin V / PEG6000 solid dispersion. The in vitro dissolution test results showed that the dissolution rate at 5 min was 53.88%, and the dissolution rate at 2 h was 63.17%. It can be seen that the solid dispersion prepared with PEG6000 as the carrier can effectively improve the dissolution behavior of celangulin V.

[0042] Example 5

[0043] Celangulin V solid dispersion, composed of celangulin V and 2-hydroxypropyl-β-cyclodextrin. By the solvent method, 1000 mg of 2-hydroxypropyl-β-cyclodextrin and 100 mg of celangulin V are dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and sieved through a 100-mesh sieve to obtain the celangulin V / 2-hydroxypropyl-β-cyclodextrin solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 34.89%, and the dissolution rate at 2 h is 67.74%. It can be seen that the solid dispersion prepared with 2-hydroxypropyl-β-cyclodextrin as the carrier can effectively improve the dissolution behavior of celangulin V.

[0044] Example 6

[0045] A celangulin V solid dispersion, composed of celangulin V, PEG6000 and 2-hydroxypropyl-β-cyclodextrin. By the solvent method, 500 mg of PEG6000, 500 mg of 2-hydroxypropyl-β-cyclodextrin and 100 mg of celangulin V are dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and sieved through a 100-mesh sieve to obtain the celangulin V / PEG6000 / 2-hydroxypropyl-β-cyclodextrin solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 49.40%, and the dissolution rate at 2 h is 71.86%. It can be seen that the solid dispersion prepared with the mixture of PEG6000 and 2-hydroxypropyl-β-cyclodextrin as the carrier can effectively improve the dissolution behavior of celangulin V.

[0046] Example 7

[0047] Celangulin V solid dispersion, composed of celangulin V, PVP K30 and PEG6000. By the solvent method, 500 mg of PEG6000, 500 mg of PVP K30 and 100 mg of celangulin V are dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and sieved through a 100-mesh sieve to obtain the celangulin V / PEG6000 / PVP K30 solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 60.50%, and the dissolution rate at 2 h is 75.72%. It can be seen that the solid dispersion prepared with the mixture of PVP K30 and PEG6000 as the carrier can effectively improve the dissolution behavior of celangulin V.

[0048] Example 8

[0049] Celangulin V solid dispersion, which is composed of celangulin V, PVP K30 and 2-hydroxypropyl-β-cyclodextrin. By using the solvent method, 500 mg of PVP K30, 500 mg of 2-hydroxypropyl-β-cyclodextrin and 100 mg of celangulin V are dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, and then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and passed through a 100-mesh sieve to obtain the celangulin V / PVP K30 / 2-hydroxypropyl-β-cyclodextrin solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 58.21%, and the dissolution rate at 2 h is 78.81%. It can be seen that the solid dispersion prepared by using the mixture of PVP K30 and 2-hydroxypropyl-β-cyclodextrin as the carrier can effectively improve the dissolution behavior of celangulin V.

[0050] Example 9

[0051] Celangulin V solid dispersion, which is composed of celangulin V, PVP K30 and 2-hydroxypropyl-β-cyclodextrin. By using the solvent method, 200 mg of PVP K30, 800 mg of 2-hydroxypropyl-β-cyclodextrin and 100 mg of celangulin V are dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, and then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and passed through a 100-mesh sieve to obtain the celangulin V / PVP K30 / 2-hydroxypropyl-β-cyclodextrin solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 81.38%, and the dissolution rate at 2 h is 86.51%.

[0052] Example 10

[0053] Celangulin V solid dispersion, which is composed of celangulin V, PVP K30 and 2-hydroxypropyl-β-cyclodextrin. By using the solvent method, 300 mg of PVP K30, 700 mg of 2-hydroxypropyl-β-cyclodextrin and 100 mg of celangulin V are dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, and then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and passed through a 100-mesh sieve to obtain the celangulin V / PVP K30 / 2-hydroxypropyl-β-cyclodextrin solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 85.36%, and the dissolution rate at 2 h is 87.02%. It can be seen that when the mixture of PVP K30 and 2-hydroxypropyl-β-cyclodextrin with a mass ratio of 3:7 is used as the carrier to prepare the solid dispersion, the dissolution behavior of celangulin V can be improved more effectively.

[0054] Example 11

[0055] Celangulin V solid dispersion, which is composed of celangulin V, PVP K30 and 2-hydroxypropyl-β-cyclodextrin. By using the solvent method, 400 mg of PVP K30, 600 mg of 2-hydroxypropyl-β-cyclodextrin and 100 mg of celangulin V are dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, and then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and passed through a 100-mesh sieve to obtain the celangulin V / PVP K30 / 2-hydroxypropyl-β-cyclodextrin solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 78.45%, and the dissolution rate at 2 h is 86.04%.

[0056] Example 12

[0057] Celangulin V solid dispersion, which is composed of celangulin V, PVP K30 and 2-hydroxypropyl-β-cyclodextrin. By using the solvent method, 600 mg of PVP K30, 400 mg of 2-hydroxypropyl-β-cyclodextrin and 100 mg of celangulin V are dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, and then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and passed through a 100-mesh sieve to obtain the celangulin V / PVP K30 / 2-hydroxypropyl-β-cyclodextrin solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 45.84%, and the dissolution rate at 2 h is 87.18%.

[0058] Example 13

[0059] Celangulin V solid dispersion, which is composed of celangulin V, PVP K30 and 2-hydroxypropyl-β-cyclodextrin. By using the solvent method, 700 mg of PVP K30, 300 mg of 2-hydroxypropyl-β-cyclodextrin and 100 mg of celangulin V are dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, and then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and passed through a 100-mesh sieve to obtain the celangulin V / PVP K30 / 2-hydroxypropyl-β-cyclodextrin solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 60.38%, and the dissolution rate at 2 h is 82.15%.

[0060] Example 14

[0061] Celangulin V solid dispersion, which consists of celangulin V, PVP K30 and 2-hydroxypropyl-β-cyclodextrin. By using the solvent method, 800 mg of PVP K30, 200 mg of 2-hydroxypropyl-β-cyclodextrin and 100 mg of celangulin V are dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, and then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and sieved through a 100-mesh sieve to obtain the celangulin V / PVP K30 / 2-hydroxypropyl-β-cyclodextrin solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 51.10%, and the dissolution rate at 2 h is 81.41%.

[0062] Example 15

[0063] Celangulin V solid dispersion, which consists of celangulin V and PVP K30. By using the solvent method, 1000 mg of PVP K30 and 100 mg of celangulin V are dissolved in ethyl acetate, ultrasonicated until clear and transparent, magnetically stirred for 1 h, and then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and sieved through a 100-mesh sieve to obtain the celangulin V / PVP K30 solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 53.32%, and the dissolution rate at 2 h is 61.24%. It can be seen that the solid dispersion prepared with PVP K30 as the carrier can effectively improve the dissolution behavior of celangulin V.

[0064] Example 16

[0065] Celangulin V solid dispersion, which consists of celangulin V and PVP K30. By using the solvent method, 1000 mg of PVP K30 and 100 mg of celangulin V are dissolved in dichloromethane, ultrasonicated until clear and transparent, magnetically stirred for 1 h, and then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and sieved through a 100-mesh sieve to obtain the celangulin V / PVP K30 solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 50.83%, and the dissolution rate at 2 h is 60.56%. It can be seen that the solid dispersion prepared with PVP K30 as the carrier can effectively improve the dissolution behavior of celangulin V.

[0066] Example 17

[0067] Celangulin V solid dispersion, which consists of celangulin V and PEG6000. By using the solvent method, 1000 mg of PEG6000 and 200 mg of celangulin V are dissolved in anhydrous methanol, ultrasonicated until clear and transparent, magnetically stirred for 1 h, and then the solvent is removed by rotary evaporation under reduced pressure. The obtained product is dried in a vacuum drying oven for 24 h, pulverized, and sieved through a 100-mesh sieve to obtain the celangulin V / PEG6000 solid dispersion. The results of in vitro dissolution experiments show that the dissolution rate at 5 min is 49.18%, and the dissolution rate at 2 h is 58.36%.

[0068] Example 18 Evaluation of the Saturated Solubility of Celangulin V Solid Dispersions

[0069] An excess of celangulin V and each solid dispersion were taken in a volumetric flask, and a certain amount of distilled water was added to obtain a supersaturated solution. The solution was placed in a water bath thermostatic oscillator (37°C, 120 r / min) and saturated for 24 h, then filtered through a 0.2-μm microporous membrane, and the collected filtrate was analyzed by HPLC. Three parallel samples of the saturated solution of each sample were prepared. The results of the saturated solubility of each sample are shown in Table 1.

[0070] Table 1 Saturated Solubility of Each Sample

[0071]

[0072]

[0073] Example 19 Study on the Insecticidal Activity of Celangulin V Solid Dispersions

[0074] 1) Contact Toxicity - Immersion Method

[0075] The celangulin V solid dispersion of Example 10 was dissolved in water to prepare a medicinal solution with a celangulin V content of 10, 20, 40, and 60 μg / mL. Thirty larvae of uniform size and good health were selected and placed in an insect immersion tube. The test insects were immersed in the medicinal solution of each concentration, taken out after 10 s, blotted dry with absorbent paper, and placed in a plastic lunch box with feed. They were cultured in a dry and well-ventilated place indoors. Water was used as a blank control, and a 6% technical drug on the market was formulated into 40 μg / mL as a control. The number of dead insects was investigated at 12, 24, 48, 72, 96, 120, 144, and 168 h after application, and the mortality rate was calculated. The results are shown in Table 2.

[0076] Table 2 Toxicity Determination of the Immersion Method against Tenebrio molitor

[0077]

[0078] 2) Stomach Toxicity - Feeding Insects with Feed Containing Drugs Method

[0079] The celangulin V solid dispersion was dissolved in water to prepare a medicinal solution with a celangulin V content of 10, 20, 40, and 60 μg / mL. Thirty larvae of uniform size and good health were selected and placed in a disposable lunch box. The mass ratio of feed to test insects was approximately 1:1. The feed was soaked in the medicinal solution of different concentrations for 30 s, and after soaking, the moisture was evaporated. They were cultured in a dry and well-ventilated place indoors. Water was used as a blank control, and a 6% technical drug on the market was formulated into 40 μg / mL as a control. The number of dead insects was investigated at 12, 24, 48, 72, 96, 120, 144, and 168 h after application, and the mortality rate was calculated. The results are shown in Table 3.

[0080] Table 3 Toxicity determination of breadworms by the method of feeding insects with feed containing drugs

[0081]

Claims

1. Celangulin V solid dispersion used as an insecticidal active substance, characterized in that, The solid dispersion is composed of celangulin V and a hydrophilic carrier; The hydrophilic carrier consists of 2-hydroxypropyl-β-cyclodextrin and PVP K30; The mass ratio of celangulin to 2-hydroxypropyl-β-cyclodextrin and PVP K30 is 1:2:8 - 1:4:6; The preparation method of the celangulin V solid dispersion is prepared according to the following steps: 1) Grind and sieve the original celangulin V drug and the hydrophilic carrier separately; 2) Weigh celangulin V and the hydrophilic carrier respectively according to the mass percentage; 3) Prepare the celangulin V solid dispersion by the solvent method.

2. The celangulin V solid dispersion used as an insecticidal active substance according to claim 1, characterized in that, The specific operation of the solvent method is as follows: Dissolve celangulin V and the hydrophilic carrier in an organic solvent, ultrasonicate or heat until clear and transparent, remove the organic solvent by rotary evaporation to precipitate celangulin V and the carrier simultaneously, dry, crush, and sieve it to obtain the celangulin V solid dispersion.

3. The celangulin V solid dispersion used as an insecticidal active substance according to claim 2, characterized in that, The organic solvent is ethanol, methanol, dichloromethane, ethyl acetate, toluene, acetone.

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