A kind of triacontanol suspension

Abstract

The invention relates to a triacontanol suspension, and belongs to the technical field of pesticides. The triacontanol suspension of the invention is prepared from the following raw materials by a hot melt condensation method: triacontanol technical, auxiliary agent and water; the auxiliary agent includes a fluxing agent and a dispersant; the triacontanol technical accounts for 5-30% of the total mass of the raw materials, and the fluxing agent accounts for 2.5-30% of the total mass of the raw materials. The triacontanol suspension of the invention has a high triacontanol content, can effectively reduce the pollution to the environment during the use of pesticides, and can greatly reduce the amount of auxiliary materials used in the production of raw materials, thereby effectively reducing production costs, reducing inventory occupied area, and reducing packaging and storage costs.

Description

Technical Field

[0001] The invention relates to a triacontanol suspension and belongs to the technical field of pesticides. Background Art

[0002] Triacontanol, also known as triacontanol, is a plant growth regulator. It was discovered by SK Ries in 1975 in a crude extract of alfalfa leaves. It is generally extracted from beeswax, bran wax or cane wax, and is also called beeswax alcohol. There are many isomers of triacontanol, among which only triacontanol-1 is physiologically active, and its structural formula is shown in Formula I.

[0003]

[0004] The main function of triacontanol is to promote plant growth, and it has an effect of increasing the yield of crops such as rice, wheat, cotton, soybeans, corn, and peanuts. In addition to being used as a plant growth regulator, studies have also found that triacontanol has varying degrees of inhibitory effects on a variety of solid tumors, such as liver cancer, intestinal cancer, and lung cancer.

[0005] The synthetic pure triacontanol is a white flaky crystal, which is almost insoluble in water, difficult to dissolve in cold methanol, ethanol, and acetone, and easily soluble in ether, chloroform, and carbon tetrachloride. Since the original triacontanol has the special properties of low fat solubility and low water solubility, triacontanol is not suitable for processing into conventional dosage forms. In addition, the active ingredient content of the existing dosage forms is generally less than 3%. When the content of triacontanol is greater than 3%, it is difficult to develop a qualified dosage form. Summary of the invention

[0006] The object of the present invention is to provide a triacontanol suspension concentrate having a higher triacontanol content.

[0007] In order to achieve the above purpose, the technical solution adopted by the present invention is:

[0008] A triacontanol suspension is prepared from the following raw materials by a hot melt coagulation method: triacontanol technical, auxiliary agent and water; the auxiliary agent comprises a fluxing agent and a dispersant; the triacontanol technical accounts for 5-30% of the total mass of the raw materials, and the fluxing agent accounts for 2.5-30% of the total mass of the raw materials.

[0009] The triacontanol suspension of the present invention is made by hot melt coagulation, the mass percentage of triacontanol can reach 5-30%, the highest 30% is more than 10 times the effective ingredient content of the commercially available triacontanol suspension product, 1 ton of mass percentage of 30% triacontanol suspension can replace at least 10 tons of commercially available products to prevent and treat crops of the same area, can effectively reduce the pollution to the environment during the use of pesticides, and can greatly reduce the amount of auxiliary materials used in production raw materials, thereby effectively reducing production costs, reducing inventory occupied area, and reducing packaging and storage and transportation costs. In a word, the triacontanol suspension of the present invention can save resources, reduce costs, and is environmentally friendly.

[0010] Further, the fluxing agent accounts for 2.5-15% of the total mass of the raw materials. Further, the fluxing agent is one or any combination of stearic acid, polyethylene glycol, and poloxamer. In the hot melt coagulation method, the fluxing agent and triacontanol are melted simultaneously to form a miscible coagulant, which can improve the stability of the triacontanol suspension. Further, the average molecular weight of the polyethylene glycol is 2000-6000, for example, the polyethylene glycol is one or any combination of polyethylene glycol 2000, polyethylene glycol 4000, and polyethylene glycol 6000. The average molecular weight of the poloxamer is 7680-9510.

[0011] The dispersant can improve the dispersion stability of triacontanol particles in the dispersion medium water. In the suspension, the dispersant is adsorbed on the surface of the pesticide particles, reduces the interfacial energy of the particles, and provides electrostatic repulsion and steric hindrance to stabilize the suspension. Further, the dispersant accounts for 3-7% of the total mass of the raw material. Further, the dispersant is one or any combination of phosphate dispersants, sulfate dispersants, and polycarboxylate dispersants; the phosphate dispersant is one or any combination of YUS-FS3000 dispersant and YUS-FS3300 dispersant; the sulfate dispersant is YUS-FS7PG dispersant; the polycarboxylate dispersant is one or any combination of YUS-CH7000 dispersant and YUS-CS300M dispersant.

[0012] Furthermore, the mass ratio of the triacontanol technical to the dispersant is 1.5 to 2.5:1, for example, 2:1.

[0013] In order to improve the wetting performance of triacontanol particles by the dispersion medium-water, the auxiliary agent further includes a wetting agent. The wetting agent accounts for 0.5-2% of the total mass of the raw material, for example, 0.5-1%; the wetting agent is a sulfonate wetting agent; the sulfonate wetting agent is one of YUS-A41B wetting agent and YUS-A51G wetting agent or any combination thereof.

[0014] Furthermore, the auxiliary agent also includes a thickener. In the processing of the water suspension, a thickener is usually added to increase the viscosity of the system, prevent the triacontanol particles from settling and agglomerating due to gravity, play a suspending role, and stabilize the storage stability of the triacontanol suspension. For the pesticide water suspension, if the viscosity is too low, it is easy to precipitate and precipitate water, resulting in low stability and affecting the use; if the viscosity is too high, the fluidity is poor, the dispersion effect is not good, it is easy to gelatinize, and the processing and use are inconvenient. In order to obtain a triacontanol suspension with better performance and convenient processing, preferably, the thickener accounts for 0.04-1% of the total mass of the raw material, for example, 0.2-1%; the thickener is one of magnesium aluminum silicate and diutan gum or any combination. When the thickener contains diutan gum, before adding diutan gum, take part of the water to prepare a diutan gum aqueous solution, and then add it to the system. The mass concentration of the diutan gum aqueous solution is preferably 2%.

[0015] Furthermore, the auxiliary agent also includes a defoamer. The defoamer can effectively eliminate the foam generated during the production process. Furthermore, the defoamer accounts for 0.1 to 0.5% of the total mass of the raw materials. The defoamer is preferably an organosilicon defoamer. For example, the organosilicon defoamer is AF1501 defoamer.

[0016] When the suspension is produced, stored and used in a low temperature environment, an antifreeze must be added to improve the stability of the suspension at low temperatures. The antifreeze changes the freezing temperature and other properties of the suspension system, thereby making the suspension have better antifreeze ability. In order to improve the low temperature stability of the suspension, the auxiliary agent further includes an antifreeze. The antifreeze accounts for 3 to 5% of the total mass of the raw materials. The antifreeze should not only have good antifreeze performance and low volatility, but also dissolve the active ingredients as low as possible. Preferably, the antifreeze is one or any combination of ethylene glycol and propylene glycol.

[0017] In order to prevent the suspension from deteriorating during storage, the auxiliary agent further includes a preservative, which accounts for 0.1 to 0.5% of the total mass of the raw materials. The preservative is preferably kason.

[0018] Furthermore, the auxiliary agent is composed of a flux, a dispersant, a wetting agent, a thickener, a defoamer, an antifreeze agent and a preservative; the flux accounts for 2.5-15% of the total mass of the raw materials, the dispersant accounts for 3-7% of the total mass of the raw materials, the wetting agent accounts for 0.5-2% of the total mass of the raw materials, the thickener accounts for 0.2-1% of the total mass of the raw materials, the defoamer accounts for 0.1-0.5% of the total mass of the raw materials, the antifreeze agent accounts for 3-5% of the total mass of the raw materials, and the preservative accounts for 0.1-0.5% of the total mass of the raw materials. Furthermore, the flux accounts for 2.5-15% of the total mass of the raw materials, the dispersant accounts for 3-7% of the total mass of the raw materials, the wetting agent accounts for 0.5-1% of the total mass of the raw materials, the thickener accounts for 0.54-1% of the total mass of the raw materials, the defoaming agent accounts for 0.1-0.5% of the total mass of the raw materials, the antifreeze accounts for 3-5% of the total mass of the raw materials, and the preservative accounts for 0.1-0.5% of the total mass of the raw materials.

[0019] Furthermore, the preparation method of the triacontanol suspension comprises the following steps: dripping the molten material uniformly mixed with the triacontanol original drug and the fluxing agent into the water phase under shearing action to solidify, and continuing to shear after the dripping is completed to obtain a sheared material; grinding the sheared material, and then adding a thickener and a preservative to mix; the water phase is composed of a dispersant, a wetting agent, an antifreeze agent, a defoamer and water. The molten material is dripped into the water phase to directly recrystallize and solidify, and after dispersion, an oil-in-water suspension system is formed, and then the original drug particles are further depolymerized by grinding, and the original drug particles are dispersed smaller, and the macromolecular dispersant replaces the fluxing agent or the wetting agent to fully modify the particles, and finally the thickener and the preservative are added to mix to form a relatively stable suspension system.

[0020] Further, the melt is formed by uniformly mixing the triacontanol technical drug and the flux from solid to liquid at a temperature higher than the melting point of the triacontanol technical drug. It is understood that the melting point of the flux is not higher than that of the triacontanol technical drug.

[0021] Furthermore, the shearing rate is controlled at 9500r / min-10000r / min, and the temperature of the system is controlled below 30°C during the shearing process. The shearing time after the dropwise addition is 20-25min. The shearing rate is 9500r / min-10000r / min.

[0022] Furthermore, the grinding is sand grinding. During grinding, the mass ratio of the shear material to the grinding medium is controlled to be 1:1-1.2, for example, 1:1.5 or 1:1.2. The grinding is sand grinding, and the grinding medium is zirconia beads with a diameter of 1.0-2.0 μm, for example, zirconia beads with a diameter of 1.8 μm.

[0023] It should be noted that the triacontanol in the present invention refers to triacontanol-1. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The particle size distribution diagram of the sheared material obtained during the preparation of the triacontanol suspension concentrate in Examples 1 to 3 and the comparative example;

[0025] Figure 2 The particle size distribution diagram of the triacontanol suspension concentrate in Examples 1 to 3 and the comparative example;

[0026] Figure 3 The photos of the storage physical stability evaluation of the triacontanol suspension in Examples 1 to 3 and the comparative example, wherein 3a is a photo of storage at room temperature for 60 days, 3b is a photo of heat storage at 54°C for 14 days, and 3c is a photo of storage at low temperature at 0°C for 7 days;

[0027] Figure 4 The particle size distribution diagram of the sheared material obtained during the preparation of the triacontanol suspension in Examples 1, 4 to 7;

[0028] Figure 5 The particle size distribution diagram of the triacontanol suspension in Examples 1, 4 to 7;

[0029] Figure 6 These are photos of the storage physical stability evaluation of the triacontanol suspension in Examples 4 to 7, wherein 6a is a photo of storage at room temperature for 60 days, 6b is a photo of heat storage at 54°C for 14 days, and 6c is a photo of low-temperature storage at 0°C for 7 days. DETAILED DESCRIPTION

[0030] The technical solution of the present invention is further described below in conjunction with specific implementation methods.

[0031] The triacontanol technical used in the following examples was purchased from Huzhou Shengtao Biotechnology Co., Ltd. with a purity of 90%; polyethylene glycol 2000, polyethylene glycol 4000, polyethylene glycol 6000, ethylene glycol and propylene glycol were all purchased from Tianjin Yongda Chemical Reagent and were all reagent pure; stearic acid was purchased from Wuhan Fengtai Weiyuan Technology Co., Ltd.; poloxamer (polymer nonionic surfactant, average molecular weight 8350) was purchased from Jiangsu Hai'an Petrochemical Plant under the trade name PLURONIC F68; YUS-FS3000 (phosphate, anionic surfactant), YUS-FS3300 (phosphate, anionic surfactant), YUS-CH7000 (polycarboxylate, anionic surfactant), YUS-CS300M (polycarboxylate, anionic surfactant), YUS-FS7PG (sulfate, anionic surfactant), YUS-A41B (sulfonate, anionic surfactant), YUS-A51G (sulfonate, anionic surfactant), all purchased from Shanghai Jieshi Chemical Co., Ltd.; magnesium aluminum silicate purchased from Shanghai Jianchao Biotechnology Co., Ltd.; diutanol purchased from Hebei Lihua Biotechnology Co., Ltd.; AF1501 (organic silicon defoamer) purchased from Guangzhou Fangzhong Chemical Co., Ltd.; Kason purchased from Shandong Xiangxin Chemical Co., Ltd. The water used in the following examples is all deionized water.

[0032] The high shear emulsifier used in the following examples is an A-25 laboratory high shear emulsifier (Shanghai Ouhe Machinery Equipment Co., Ltd.), and the sand mill used is an SM-0.2L laboratory sand mill (vertical sand mill, Jiangyin Zhuoying Drying Engineering Technology Co., Ltd.).

[0033] Examples 1 to 19

[0034] The triacontanol suspension concentrates of Examples 1 to 19 are all prepared from the following raw materials by hot melt coagulation: triacontanol technical, a flux, a dispersant and deionized water; the preparation method of the triacontanol suspension concentrates of Examples 1 to 19 comprises the following steps:

[0035] 1) melting the triacontanol technical and the flux at 95° C. and stirring evenly to obtain a molten slurry;

[0036] Mix deionized water and dispersant and stir evenly to obtain a water phase;

[0037] 2) The aqueous phase is transferred to a high shear emulsifier, and circulating cooling water of the aqueous phase is connected. The molten slurry is slowly added dropwise to the aqueous phase under high-speed shearing. After the addition is completed, the shearing is continued for 25 minutes to obtain a sheared material. During the process of adding the molten slurry dropwise and the process of continuous shearing after the addition is completed, the shear rate is controlled to be 10000r / min, and the system temperature is maintained below 30°C;

[0038] 3) The sheared material was transferred to the grinding cylinder of the sand mill, and the grinding medium (the grinding medium was zirconia beads with a diameter of 1.8 μm) was added according to the material mass: grinding medium mass = 1:1.2, the speed was maintained at 1400 r / min, and sand milled for 2 h to obtain the triacontanol suspension.

[0039] In Examples 1 to 11, the percentages of triacontanol technical, fluxing agent, dispersant and water in the total mass of raw materials in each example are shown in Table 1, and the fluxing agent and dispersant used in each example are also shown in Table 1.

[0040] In Examples 12 to 19, the percentages of triacontanol technical, fluxing agent, dispersant and water in the total mass of raw materials in each example are shown in Table 1, and the fluxing agent and dispersant used in each example are also shown in Table 2.

[0041] Table 1 The percentage of triacontanol technical, fluxing agent, dispersant and water in the total mass of raw materials in Examples 1 to 11 (%) and the specific fluxing agent and dispersant used in Examples 1 to 11

[0042]

[0043] Table 2 The percentage of triacontanol technical, fluxing agent, dispersant and water in the total mass of raw materials in Examples 12 to 19 and the specific fluxing agent and dispersant used in Examples 12 to 19

[0044]

[0045]

[0046] Examples 20 to 27

[0047] The triacontanol suspensions of Examples 20 to 27 are all prepared from the following raw materials by hot melt coagulation: triacontanol technical, a flux, a dispersant, a wetting agent and deionized water; the preparation method of the triacontanol suspensions of Examples 20 to 27 comprises the following steps:

[0048] 1) melting the triacontanol technical and the eutectic at 95° C. and stirring evenly to obtain a molten slurry;

[0049] Mix deionized water, a dispersant and a wetting agent and stir them uniformly to obtain a water phase;

[0050] 2) The aqueous phase is transferred to a high-speed shear emulsifier, and circulating cooling water of the aqueous phase is connected. The molten slurry is slowly added dropwise to the aqueous phase under high-speed shearing. After the addition is completed, the shearing is continued for 25 minutes to obtain a sheared material. During the process of adding the molten slurry dropwise and the process of continuous shearing after the addition is completed, the shear rate is controlled to be 10000r / min, and the system temperature is maintained below 30°C;

[0051] 3) The sheared material was transferred to the grinding cylinder of the sand mill, and the grinding medium (the grinding medium was zirconia beads with a diameter of 1.8 μm) was added according to the material mass: grinding medium mass = 1:1.2, the rotation speed was maintained at 1400 r / min, and sand milled for 2 h to obtain triacontanol suspension.

[0052] The ratio of triacontanol technical, fluxing agent, dispersant, wetting agent and water to the total mass of raw materials in Examples 20 to 27 and the specific fluxing agent, dispersant and wetting agent used are shown in Table 3.

[0053] Table 3 The ratio of triacontanol technical, fluxing agent, dispersant, wetting agent and water to the total mass of raw materials in Examples 20-27 and the specific fluxing agent, dispersant and wetting agent used

[0054]

[0055] Embodiments 28 to 35

[0056] The triacontanol suspensions of Examples 28 to 35 are all prepared from the following raw materials using a hot melt coagulation method: triacontanol technical, a flux, a dispersant, a wetting agent, a thickener and deionized water.

[0057] Wherein, the preparation method of the triacontanol suspension concentrate of Examples 28 to 30 comprises the following steps:

[0058] 1) melting the triacontanol technical and the flux at 95° C. and stirring evenly to obtain a molten slurry;

[0059] Taking part of the deionized water and adding diutanol to dissolve it, so as to obtain a diutanol solution with a diutanol concentration of 2%;

[0060] The remaining deionized water, dispersant and wetting agent are mixed and stirred uniformly to obtain a water phase;

[0061] 2) The aqueous phase is transferred to a high-speed shear emulsifier, and circulating cooling water of the aqueous phase is connected. The molten slurry is slowly added dropwise to the aqueous phase under high-speed shearing. After the addition is completed, the shearing is continued for 25 minutes to obtain a sheared material. During the process of adding the molten slurry dropwise and the process of continuous shearing after the addition is completed, the shear rate is controlled to be 10000r / min, and the system temperature is maintained below 30°C;

[0062] 3) Transfer the sheared material to the grinding cylinder of the sand mill, add grinding media (the grinding media is zirconia beads with a diameter of 1.8 μm) according to the material mass: grinding media mass = 1:1.2, maintain the speed at 1400 r / min, and sand grind for 2 hours;

[0063] 4) Add a thickener to the sand-milled slurry in proportion, stir at a stirring rate of 500 r / min, and complete the processing after stirring for 30 minutes to obtain a triacontanol suspension.

[0064] Wherein, the preparation method of the triacontanol suspension concentrate of Examples 31 to 33 comprises the following steps:

[0065] 1) melting the triacontanol technical and the flux at 95° C. and stirring evenly to obtain a molten slurry;

[0066] Mix deionized water, dispersant and wetting agent and stir evenly to obtain a water phase;

[0067] 2) The aqueous phase is transferred to a high-speed shear emulsifier, and circulating cooling water of the aqueous phase is connected. The molten slurry is slowly added dropwise to the aqueous phase under high-speed shearing. After the addition is completed, the shearing is continued for 25 minutes to obtain a sheared material. During the process of adding the molten slurry dropwise and the process of continuous shearing after the addition is completed, the shear rate is controlled to be 10000r / min, and the system temperature is maintained below 30°C;

[0068] 3) Transfer the sheared material to the grinding cylinder of the sand mill, add grinding media (the grinding media is zirconia beads with a diameter of 1.8 μm) according to the material mass: grinding media mass = 1:1.2, maintain the speed at 1400 r / min, and sand grind for 2 hours;

[0069] 4) Add a thickener to the sand-milled slurry in proportion, stir at a stirring rate of 500 r / min, and complete the processing after stirring for 30 minutes to obtain a triacontanol suspension.

[0070] Wherein, the preparation method of the triacontanol suspension concentrate of Examples 34 to 35 comprises the following steps:

[0071] 1) melting the triacontanol technical and the flux at 95° C. and stirring evenly to obtain a molten slurry;

[0072] Taking part of the deionized water and adding diutanol to dissolve it, so as to obtain a diutanol solution with a diutanol concentration of 2%;

[0073] The remaining deionized water, dispersant and wetting agent are mixed and stirred uniformly to obtain a water phase;

[0074] 2) The aqueous phase is transferred to a high-speed shear emulsifier, and circulating cooling water of the aqueous phase is connected. The molten slurry is slowly added dropwise to the aqueous phase under high-speed shearing. After the addition is completed, the shearing is continued for 25 minutes to obtain a sheared material. During the process of adding the molten slurry dropwise and the process of continuous shearing after the addition is completed, the shear rate is controlled to be 10000r / min, and the system temperature is maintained below 30°C;

[0075] 3) Transfer the sheared material to the grinding cylinder of the sand mill, add grinding media (the grinding media is zirconia beads with a diameter of 1.8 μm) according to the material mass: grinding media mass = 1:1.2, maintain the speed at 1400 r / min, and sand grind for 2 hours;

[0076] 4) Add diutanol solution and aluminum magnesium silicate to the sand-milled slurry in proportion, stir at a stirring rate of 500 r / min for 30 min to complete the processing and obtain triacontanol suspension.

[0077] The percentage of triacontanol technical, fluxing agent, dispersant, wetting agent, thickener and water used in Examples 28 to 35 in the total mass of the raw materials and the specific fluxing agent, dispersant, wetting agent and thickener used therein are shown in Table 4.

[0078] Table 4 The percentage of triacontanol technical, fluxing agent, dispersant, wetting agent, thickener and water used in Examples 28 to 35 in the total mass of raw materials and the specific fluxing agent, dispersant, wetting agent and thickener used in the examples

[0079]

[0080] Embodiments 36 to 51

[0081] The triacontanol suspension concentrates of Examples 36 to 51 are all prepared by hot melt coagulation from the following raw materials: triacontanol technical, a flux, a dispersant, a wetting agent, a thickener, a defoaming agent, an antifreeze agent, a preservative and deionized water; the preparation method of the triacontanol suspension concentrates of Examples 36 to 45 and 48 to 51 comprises the following steps:

[0082] 1) melting the triacontanol technical and the eutectic at 95° C., stirring evenly to obtain a molten slurry for later use;

[0083] Taking part of the deionized water and adding diutanol to dissolve it, so as to obtain a diutanol solution with a diutanol concentration of 2%;

[0084] The remaining deionized water, dispersant, wetting agent, antifreeze agent and defoamer are mixed and stirred uniformly to obtain an aqueous phase;

[0085] 2) The aqueous phase is transferred to a high-speed shear emulsifier, and circulating cooling water of the aqueous phase is connected. The molten slurry is slowly added dropwise to the aqueous phase under high-speed shearing. After the addition is completed, the shearing is continued for 25 minutes to obtain a sheared material. During the process of adding the molten slurry dropwise and the process of continuous shearing after the addition is completed, the shear rate is controlled to be 10000r / min, and the system temperature is maintained below 30°C;

[0086] 3) Transfer the sheared material to the grinding cylinder, add grinding media (the grinding media is zirconia beads with a diameter of 1.8 μm) according to the ratio of material mass to grinding media mass = 1:1.2, maintain the speed at 1400 r / min, and sand grind for 2 hours;

[0087] 4) Add dimethoate solution, aluminum magnesium silicate and preservative to the sand-ground slurry in proportion, and stir for 30 minutes at a stirring rate of 500 r / min to complete the processing.

[0088] The preparation method of the triacontanol suspension of Example 46 comprises the following steps:

[0089] 1) melting the triacontanol technical and the eutectic at 95° C., stirring evenly to obtain a molten slurry for later use;

[0090] Taking part of the deionized water and adding diutanol to dissolve it, so as to obtain a diutanol solution with a diutanol concentration of 2%;

[0091] The remaining deionized water, dispersant, wetting agent, antifreeze agent and defoamer are mixed and stirred uniformly to obtain an aqueous phase;

[0092] 2) The aqueous phase is transferred to a high-speed shear emulsifier, and circulating cooling water of the aqueous phase is connected. The molten slurry is slowly added dropwise to the aqueous phase under high-speed shearing. After the addition is completed, the shearing is continued for 25 minutes to obtain a sheared material. During the process of adding the molten slurry dropwise and the process of continuous shearing after the addition is completed, the shear rate is controlled to be 10000r / min, and the system temperature is maintained below 30°C;

[0093] 3) Transfer the sheared material to the grinding cylinder, add grinding media (the grinding media is zirconia beads with a diameter of 1.8 μm) according to the ratio of material mass to grinding media mass = 1:1.2, maintain the speed at 1400 r / min, and sand grind for 2 hours;

[0094] 4) Add dimethoate solution and preservative to the sand-ground slurry in proportion, and stir for 30 minutes at a stirring rate of 500 r / min to complete the processing.

[0095] The preparation method of the triacontanol suspension of Example 47 comprises the following steps:

[0096] 1) melting the triacontanol technical and the eutectic at 95° C., stirring evenly to obtain a molten slurry for later use;

[0097] The remaining deionized water, dispersant, wetting agent, antifreeze agent and defoamer are mixed and stirred uniformly to obtain an aqueous phase;

[0098] 2) The aqueous phase is transferred to a high-speed shear emulsifier, and circulating cooling water of the aqueous phase is connected. The molten slurry is slowly added dropwise to the aqueous phase under high-speed shearing. After the addition is completed, the shearing is continued for 25 minutes to obtain a sheared material. During the process of adding the molten slurry dropwise and the process of continuous shearing after the addition is completed, the shear rate is controlled to be 10000r / min, and the system temperature is maintained below 30°C;

[0099] 3) Transfer the sheared material to the grinding cylinder, add grinding media (the grinding media is zirconia beads with a diameter of 1.8 μm) according to the ratio of material mass to grinding media mass = 1:1.2, maintain the speed at 1400 r / min, and sand grind for 2 hours;

[0100] 4) Add aluminum magnesium silicate and preservatives to the sand-ground slurry in proportion, and stir for 30 minutes at a stirring rate of 500 r / min to complete the processing.

[0101] The percentage of triacontanol technical, fluxing agent, dispersant, wetting agent, thickener, defoamer, antifreeze agent, preservative and water used in Examples 36 to 51 in the total mass of raw materials and the specific fluxing agent, dispersant, wetting agent, defoamer, antifreeze agent and preservative used therein are shown in Tables 5 and 6.

[0102] Table 5 Percentage of triacontanol technical, fluxing agent, dispersant, wetting agent, thickener, defoamer, antifreeze agent, preservative and water used in Examples 36 to 43 in the total mass of raw materials and the specific fluxing agent, dispersant, wetting agent, thickener, defoamer, antifreeze agent and preservative used in the examples

[0103]

[0104]

[0105] Table 6 Percentage of triacontanol technical, fluxing agent, dispersant, wetting agent, thickener, defoamer, antifreeze agent, preservative and water used in Examples 44 to 51 in the total mass of raw materials and the specific fluxing agent, dispersant, wetting agent, thickener, defoamer, antifreeze agent and preservative used in the examples

[0106]

[0107] Comparative Example

[0108] The triacontanol suspension of this comparative example is made of the following raw materials: triacontanol original drug, dispersant and deionized water; the mass ratio of the triacontanol original drug, dispersant and deionized water used in the dispersant is 5:3:92; the dispersant used is YUS-FS3000. The preparation method of the triacontanol suspension of this embodiment comprises the following steps:

[0109] 1) melting triacontanol technical at 95° C. to obtain a molten slurry;

[0110] Mix deionized water and dispersant and stir evenly to obtain a water phase;

[0111] 2) The aqueous phase is transferred to a high shear emulsifier, and circulating cooling water of the aqueous phase is connected. The molten slurry is slowly added dropwise to the aqueous phase under high-speed shearing. After the addition is completed, the shearing is continued for 25 minutes to obtain a sheared material. During the process of adding the molten slurry dropwise and the process of continuous shearing after the addition is completed, the shear rate is controlled to be 10000r / min, and the system temperature is maintained below 30°C;

[0112] 3) The sheared material was transferred to the grinding cylinder of the sand mill, and the grinding medium (the grinding medium was zirconia beads with a diameter of 1.8 μm) was added according to the material mass: grinding medium mass = 1:1.2, the rotation speed was maintained at 1400 r / min, and sand milled for 2 h to obtain triacontanol suspension.

[0113] In the following experimental example:

[0114] 1) The particle size distribution was determined by referring to the laser particle size method in NY / T 1860.32 using a BT-9300ST laser particle size distribution analyzer (Dandong Better Instrument Co., Ltd.); the measurement was repeated three times and the average value was taken. In general, the D90 particle size of the suspension is required to be below 10 μm.

[0115] 2) Heat storage stability is tested in accordance with the method in GB / T 19136. About 30 mL of the suspension sample is injected into a clean ampoule with a syringe (to avoid contact between the sample and the bottleneck), sealed with a high-temperature flame (to avoid solvent volatilization), and stored at (54±2)℃ for 14 days. After that, it is restored to room temperature. After returning to room temperature, observe whether the appearance changes, whether the fluidity is good, and whether water precipitation occurs. It is required that the appearance does not change, the fluidity is good, and the water precipitation rate is less than 5% to be qualified. Select qualified samples to test their active ingredient content and calculate their active ingredient decomposition rate. The active ingredient decomposition rate after heat storage is less than 5% to be qualified.

[0116]

[0117] Where:

[0118] W0: the content of active ingredient measured by the sample retained at room temperature (%);

[0119] W1: The content of active ingredients measured after hot storage of the sample (%).

[0120] The water separation rate after storage at (54±2)℃ for 14 days is calculated according to the following formula:

[0121]

[0122] Where:

[0123] h0: height from the initial liquid level to the bottom of the suspension sample before hot storage (cm);

[0124] h1: height of the water separation layer of the suspension sample after hot storage (cm);

[0125] 3) The viscosity was measured by using NDJ-8S rotary viscometer (Shanghai Youyi Instrument Co., Ltd.) according to the method in NY / T 1860.21 to automatically measure the viscosity of the test object at 20°C; the suspension viscosity value was measured by selecting rotor No. 2, with a speed of 30r / min, and the suspension to be measured was fixed so that the rotor would not touch the wall during the measurement process. The measurement was repeated 3 times and the average value was taken. The viscosity was qualified if it was below 800mPa·s.

[0126] 4) pH determination is carried out in accordance with the method in GB / T 1601; before the determination, the instrument is calibrated with a standard buffer solution, and the cleaned electrode is inserted into the diluted sample solution (the dilution factor is 100 times) to determine its pH value. Repeat 3 times and take the average value. The pH value is qualified when it is between 5.0 and 8.0.

[0127] 5) Pourability is measured according to the method in GB / T 31737; the sample is considered qualified if the residue after pouring is less than 5% and the residue after washing is less than 0.5%.

[0128] ① Determination of dumpable residues

[0129] Weigh the mass of the measuring cylinder with stopper, add the sample to the mark where the total volume of the measuring cylinder is 80%, cover it with a lid, and weigh it again. Let it stand at room temperature for 24 hours, first rotate the measuring cylinder 135° from the upright position, tilt it for 60 seconds, then invert it for 60 seconds, and weigh the mass of the measuring cylinder again.

[0130] Calculate the residue after pouring the sample.

[0131]

[0132] Where:

[0133] M0: mass of the stoppered measuring cylinder (g);

[0134] M1: the sum of the sample mass and the stoppered measuring cylinder mass (g);

[0135] M2: the sum of the mass of the residue after pouring and the mass of the stoppered measuring cylinder (g);

[0136] ② Determination of residue after washing

[0137] Add distilled water to the 80% mark of the total volume of the measuring cylinder, cover the lid, and invert the measuring cylinder 180° up and down 10 times (2 seconds each time) with the center of the measuring cylinder as the center. First, rotate the measuring cylinder 135° from the upright position, tilt it for 60 seconds, and then invert it for 60 seconds, and re-weigh the mass of the measuring cylinder. Calculate the residue after the sample is washed.

[0138]

[0139] Where:

[0140] M0: mass of the stoppered measuring cylinder (g);

[0141] M1: the sum of the sample mass and the stoppered measuring cylinder mass (g);

[0142] M2: the sum of the mass of the residue after pouring and the mass of the stoppered measuring cylinder (g);

[0143] M3: The sum of the mass of the residue after washing and the mass of the stoppered measuring cylinder (g).

[0144] 6) The persistent foaming property is tested according to the method in GB / T 28137. Add standard hard water to a 250mL measuring cylinder to the 180mL mark, place the measuring cylinder on a balance, weigh 1.0g of the sample, add hard water to the 9cm mark at the bottom of the measuring cylinder stopper, cover the stopper, and turn the measuring cylinder upside down 180° 30 times (2s each time) with the middle of the measuring cylinder as the center. Place it vertically on the test bench and let it stand. Record the foam volume at 1min±10s, repeat three times, and take the average value as the persistent foaming property test result of the sample. The persistent foaming property is qualified if it is less than 60mL.

[0145] 7) The suspension rate determination is carried out in accordance with the method in GB / T 14825. Weigh an appropriate amount of sample into a 250mL measuring cylinder, add standard hard water to fill up to the scale, turn it upside down 30 times continuously, open the stopper, vertically place it in a 30℃ constant temperature water bath and let it stand for 30 minutes, use a pipette to remove 9 / 10 (i.e. 225mL) of the suspension in 10-15s, determine the mass of the active ingredient in the sample and the lower 1 / 10 (i.e. 25mL) of the suspension in the measuring cylinder according to the prescribed method, and calculate the suspension rate. A suspension rate greater than 90% is qualified.

[0146]

[0147] Where:

[0148] m0: the mass of the active ingredient in the sample taken to prepare the suspension (g);

[0149] m1: the mass of the active ingredient in the remaining 1 / 10 suspension at the bottom (g);

[0150] Conversion factor.

[0151] Determination of active ingredient content:

[0152] Preparation of standard sample: Weigh 0.02 g (accurate to 0.0002 g) of triacontanol standard into a 100 mL volumetric flask, dissolve it completely with chloroform, accurately add 1 mL of internal standard solution, dissolve it with chloroform and dilute to the scale, and shake well.

[0153] Sample preparation: Weigh 0.3 g (accurate to 0.0002 g) of the sample into a 100 mL beaker, dry it in an open oven at 55°C until it is nearly dry (without moisture), cool it to room temperature, accurately add 24 mL of chloroform for ultrasonication, accurately add 1 mL of internal standard solution, ultrasonicate, and shake well.

[0154] Determination: Under the set chromatographic conditions, after the instrument baseline is stable, continuously inject several injections of standard solution, calculate the relative response value of each injection, and when the relative deviation of the peak area of ​​two adjacent injections of triacontanol and the internal standard is less than 1.0%, perform gas chromatography analysis in the following order: standard solution, sample solution, sample solution, standard solution.

[0155] The peak areas of triacontanol in the two sample solutions and the two standard solutions were averaged, and the mass fraction of triacontanol in the sample was calculated as follows:

[0156]

[0157] Where:

[0158] r1——the average value of the ratio of the peak area of ​​triacontanol in the standard solution to the peak area of ​​the internal standard;

[0159] r2——the average value of the ratio of the peak area of ​​triacontanol in the sample solution to the peak area of ​​the internal standard;

[0160] m1——mass of triacontanol (g);

[0161] m2——mass of the sample (g);

[0162] p——mass fraction of triacontanol in standard sample (%).

[0163] 8) Low temperature stability is tested in accordance with the method in GB / T 19137. Use a syringe to inject about 30 mL of the suspension sample into a clean ampoule (avoid the sample from contacting the bottleneck), seal it with a high temperature flame (avoid solvent volatilization), store it at (0±2)℃ for 7 days, and then restore it to room temperature. After returning to room temperature, observe whether the appearance changes, whether the fluidity is good, whether there is water precipitation, etc. It is qualified if there is no change in appearance, good fluidity, and water precipitation rate is less than 5%.

[0164] Experimental Example 1

[0165] The particle size distribution of the sheared material, the particle size distribution of the triacontanol suspension obtained after sand grinding, and the thermal storage stability of the triacontanol suspension in the preparation methods of Examples 1 to 7 and the comparative example were tested, and the results are shown in Figures 7 and Figures 1 to 6 .

[0166] Table 7 Changes in sheared material and suspension particle size and thermal storage stability of suspension

[0167]

[0168] Compare the data of Examples 1 to 3 and the comparative example in Table 7 and combine Figures 1 to 3 It can be seen that the amount of fluxing agent has a great influence on the particle size distribution during the processing of the suspension agent; among them, the particle size of the sheared material decreases with the increase of the amount of polyethylene glycol 6000, and when the mass ratio of triacontanol to polyethylene glycol 6000 is ≤1, the particle size distribution is not much different; but after sand grinding, the particle size distribution of the suspension agent of Example 1 is narrower, the suspension agent of Example 2 is second, the particle size distribution of the suspension agent of Example 3 is relatively slightly wider, and the suspension agent of the comparative example is the worst. It shows that the addition of fluxing agent can make the small particles of triacontanol more evenly distributed and the particle size smaller; the results of heat storage 14D also show that the stability of the triacontanol suspension agent of Example 1 is the best.

[0169] The melting points of the selected fluxes in Examples 1 and 4 to 7 are all below 70° C. (wherein the melting range of polyethylene glycol 2000 is 51.3-53.4° C., the melting range of polyethylene glycol 4000 is 59.3-60.1° C., the melting range of polyethylene glycol 6000 is 59.4-62.8, the melting range of stearic acid is 68.2-69.3° C., and the melting range of poloxamer is 55.4-58.7° C.), and are all lower than the melting point of triacontanol (the melting range of triacontanol is 83.5-85.5° C.);

[0170] Compare the data of Examples 1, 4 to 7 in Table 7 and combine Figures 4 to 6 It can be seen that the particle size of the sheared material is larger, and the particle size will be greatly reduced after sand grinding. The particle size distribution of the triacontanol suspension of Example 1 and Example 5 after sand grinding is not much different, and the particle size distribution is relatively narrow; the triacontanol suspension of Examples 4, 6 and 7 is not much different, and the particle size distribution is relatively slightly wider; the hot storage results also show that the triacontanol suspension of Examples 1 and 5 has a lower water separation rate and better stability.

[0171] Experimental Example 2

[0172] In the preparation methods of the triacontanol suspension concentrates of Examples 8 to 15, the viscosity of the sheared material and the viscosity of the triacontanol suspension concentrate obtained after sand grinding were tested, and the results are shown in Table 8.

[0173] Table 8 Viscosity response of triacontanol suspension concentrates of Examples 8 to 15

[0174] Example Viscosity after shearing / mPa·s Viscosity after sanding / mPa·s Judgment results 8 39.6 88 qualified 9 215.6 385.3 qualified 10 398.2 540.3 qualified 11 897.6 - Failure 12 349.7 509.2 qualified 13 298.6 464.3 qualified 14 369.5 498.2 qualified 15 420.8 529.1 qualified

[0175] “-” represents paste.

[0176] From the data of Examples 8-11 in Table 8, it can be seen that the amount of dispersant used affects the viscosity of the suspension. As the drug loading increases, the viscosity of the suspension increases significantly; but its viscosity after shearing is quite different from that after sand grinding. The reason is that as the drug loading increases, the proportion of the molten slurry increases, which makes it more difficult to disperse during shearing, and often forms larger lumps that cannot be sheared. After sand grinding, the dispersion is more uniform, resulting in an increase in viscosity. It can be clearly seen from the above table that Example 11 is directly paste-formed after sand grinding, and Examples 8 to 10 have good appearance.

[0177] From the data of Examples 10, 12 to 15 in Table 8, it can be seen that as the proportion of dispersant increases from 3% to 7%, the viscosity of the triacontanol suspension decreases first and then increases. When the amount of dispersant is small, the interfacial energy of the original drug can continue to decrease, so the viscosity decreases as the amount of dispersant increases. When the drug particles reach saturated adsorption, the amount of dispersant continues to increase, resulting in vacancy flocculation and increased viscosity of the system. When the proportion of dispersant is 5%, the viscosity of the triacontanol suspension is the lowest.

[0178] Experimental Example 3

[0179] The suspension rates of the triacontanol suspension concentrates of Examples 13 to 27 were measured respectively, wherein the suspension rate results of the triacontanol suspension concentrates of Examples 13 to 19 are shown in Table 9, and the suspension rates of the triacontanol suspension concentrates of Examples 20 to 27 are shown in Table 10.

[0180] Table 9 Suspension rate of triacontanol suspension concentrate of Examples 14 to 20

[0181] Example 13 16 17 18 19 Suspension rate / % 92.3 93.7 85.3 87.6 82.3

[0182] Comparing the suspension rates of the triacontanol suspension concentrates of Examples 13 to 19, it can be seen that the effects of different dispersants on the suspension rates of the triacontanol suspension concentrates are quite different. The suspension rates of the suspension concentrates whose dispersants are YUS-FS3000 and YUS-FS3300 are both greater than 90%, and the suspension rates of the suspension concentrates whose dispersants are YUS-FS7PG, YUS-CH7000 and YUS-CS300M are less than 90%.

[0183] Table 10 Suspension rate of triacontanol suspension concentrate of Examples 20 to 27

[0184] Example 20 21 22 23 24 25 26 27 Suspension rate / % 98.6 88.9 86.5 87.3 98.3 84.6 87.1 81.9

[0185] When two or more surfactant solutions are mixed with each other, the properties of the mixed solution are different from those of the individual surfactants. Due to molecular interactions, complex formation, electrostatic attraction, or repulsion, as well as other physical or chemical interactions, synergistic or antagonistic effects are produced. If the effect produced after mixing is better than that of the individual components, it is called a synergistic effect; if the opposite is true, it is called an antagonistic effect.

[0186] Comparing the suspension rates of the triacontanol suspension concentrates of Examples 20 to 27, it can be seen that when the wetting agent is YUS-A41B and the amount is 0.5%, the suspension rate of the suspension concentrate is improved, while when the amount is increased to 1%, the suspension rate decreases instead; when the wetting agent is YUS-A51G, the suspension rate decreases at 0.5% and 1%. It can be seen that when the dispersants YUS-FS3000 and YUS-FS3300 are combined with 0.5% YUS-A41B wetting agent, a synergistic effect is produced, which increases the suspension rate of the suspension concentrate.

[0187] Experimental Example 4

[0188] The viscosity of the triacontanol suspension concentrates of Examples 28 to 35 was measured respectively. The results are shown in Table 11.

[0189] Table 11 Viscosity of the triacontanol suspension of Examples 28 to 35

[0190]

[0191]

[0192] It can be seen from Table 11 that the viscosity of diutanol or magnesium aluminum silicate suspension alone is basically below 400 mPa·s. When the two are compounded, the viscosity increases significantly. Among them, the combination of 0.08% diutanol + 0.5% magnesium aluminum silicate has the best effect, and the suspension viscosity is 459.7 mPa·s, which is more suitable and has good fluidity.

[0193] Experimental Example 5

[0194] The low temperature stability of the triacontanol suspension concentrates of Examples 36 to 41 was measured to determine whether they were qualified. The results are shown in Table 12.

[0195] Table 12 Low temperature stability of triacontanol suspensions of Examples 36 to 41

[0196] Example 36 37 38 39 40 41 Judgment results Failure qualified qualified Failure qualified qualified

[0197] It can be seen from Table 12 that when the dosage of ethylene glycol and propylene glycol is 3-5%, the antifreeze effect is good and the suspension system will not be adversely affected. In order to save costs, ethylene glycol is selected as the antifreeze agent with a dosage of 3%.

[0198] Experimental Example 6

[0199] The performance of the triacontanol suspension concentrates of Examples 42 to 51 were tested respectively. The results are shown in Table 13.

[0200] Table 13 Performance test results of triacontanol suspension concentrates of Examples 42 to 51

[0201]

[0202]

[0203] As shown in Table 13, all the indicators of the triacontanol suspension concentrates of Examples 42 to 51 are qualified.

Claims

1. A triacontanol suspension concentrate, characterized in that: The invention is prepared from the following raw materials by hot melt coagulation method: triacontanol technical, auxiliary agent and water; the auxiliary agent comprises a fluxing agent and a dispersing agent; the fluxing agent is polyethylene glycol, and the average molecular weight of the polyethylene glycol is 4000-6000; the triacontanol technical accounts for 5-30% of the total mass of the raw materials, the fluxing agent accounts for 2.5-10% of the total mass of the raw materials, and the dispersing agent accounts for 3-7% of the total mass of the raw materials.

2. The triacontanol suspension according to claim 1, wherein: The fluxing agent accounts for 2.5-15% of the total mass of the raw materials.

3. The triacontanol suspension according to claim 1, wherein: The dispersant is one or any combination of a phosphate dispersant, a sulfate dispersant, and a polycarboxylate dispersant.

4. The triacontanol suspension according to claim 1, wherein: The auxiliary agent also includes a wetting agent, which accounts for 0.5-2% of the total mass of the raw materials; the wetting agent is a sulfonate wetting agent.

5. The triacontanol suspension according to claim 1, wherein: The auxiliary agent also includes a thickener, and the thickener accounts for 0.04-1% of the total mass of the raw materials.

6. The triacontanol suspension according to claim 1, wherein: The auxiliary agent also includes a defoamer, which accounts for 0.1-0.5% of the total mass of the raw materials; the defoamer is an organic silicon defoamer.

7. The triacontanol suspension according to claim 1, wherein: The auxiliary agent also includes antifreeze agent, and the antifreeze agent accounts for 3-5% of the total mass of the raw materials.

8. The triacontanol suspension according to claim 1, wherein: The auxiliary agent also includes a preservative, and the preservative accounts for 0.1-0.5% of the total mass of the raw material.

9. The triacontanol suspension concentrate according to any one of claims 1 to 8, characterized in that: The auxiliary agent consists of a flux, a dispersant, a wetting agent, a thickener, a defoamer, an antifreeze agent and a preservative; the flux accounts for 2.5-15% of the total mass of the raw materials, the wetting agent accounts for 0.5-2% of the total mass of the raw materials, the thickener accounts for 0.2-1% of the total mass of the raw materials, the defoamer accounts for 0.1-0.5% of the total mass of the raw materials, the antifreeze agent accounts for 3-5% of the total mass of the raw materials, and the preservative accounts for 0.1-0.5% of the total mass of the raw materials.

10. The triacontanol suspension concentrate according to claim 9, characterized in that: The preparation method of the triacontanol suspension comprises the following steps: dripping a molten product uniformly mixed with triacontanol technical and a flux into a water phase under shearing action to solidify, and continuing to shear after the dripping is completed to obtain a sheared material; grinding the sheared material, and then adding a thickener and a preservative to mix; the water phase is composed of a dispersant, a wetting agent, an antifreeze agent, a defoaming agent and water.

Images