CN116019092A

CN116019092A - Triacontanol suspending agent

Info

Publication number: CN116019092A
Application number: CN202211262200.5A
Authority: CN
Inventors: 郑先福; 李明; 龚梦华
Original assignee: ZHENGZHOU ZHENGSHI CHEMICAL PRODUCT CO Ltd
Current assignee: ZHENGZHOU ZHENGSHI CHEMICAL PRODUCT CO Ltd
Priority date: 2022-10-14
Filing date: 2022-10-14
Publication date: 2023-04-28

Abstract

The invention relates to a triacontanol suspending agent, and belongs to the technical field of pesticides. The triacontanol suspending agent is prepared from the following raw materials by a thermal fusion polymerization method: triacontanol original medicine, auxiliary agent and water; the auxiliary agent comprises a mixed solvent and a dispersing agent; the triacontanol raw medicine accounts for 5-30% of the total mass of the raw materials, and the mixed solvent accounts for 2.5-30% of the total mass of the raw materials. The triacontanol suspending agent has higher triacontanol content, can effectively reduce the pollution to the environment in the using process of pesticides, and can greatly reduce the consumption of auxiliary materials on production raw materials, thereby effectively reducing the production cost, reducing the occupied area of the stock and the cost of packaging and storing and transporting.

Description

Triacontanol suspending agent

Technical Field

The invention relates to a triacontanol suspending agent, and belongs to the technical field of pesticides.

Background

Triacontanol, also known as triacontanol, is a plant growth regulating substance. Riss (S.K.Ries) was found in 1975 in the crude extract of alfalfa leaves. Is typically extracted from beeswax, bran wax or cane wax, also known as beeswax alcohol. The triacontanol has a plurality of isomers, wherein only triacontanol-1 has physiological activity, and the structural formula is shown as a formula I.

The triacontanol has the main function of promoting plant growth and has yield increasing effect on crops such as rice, wheat, cotton, soybean, corn, peanut and the like; in addition to use as plant growth regulator, triacontanol has also been found to have various degrees of inhibition on solid tumors such as liver cancer, intestinal cancer, lung cancer, etc.

The synthesized triacontanol is white scale-like crystal, is hardly soluble in water, is hardly soluble in cold methanol, ethanol and acetone, and is easily soluble in diethyl ether, chloroform and carbon tetrachloride. Triacontanol is not suitable for processing into conventional dosage forms because of its particular low fat-soluble, low water-soluble nature. And the content of active ingredients of the existing dosage forms is generally lower than 3%, and when the content of triacontanol is more than 3%, the qualified dosage forms are difficult to develop.

Disclosure of Invention

The invention aims to provide a triacontanol suspending agent with higher triacontanol content.

In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:

a triacontanol suspending agent is prepared from the following raw materials by a thermal fusion polymerization method: triacontanol original medicine, auxiliary agent and water; the auxiliary agent comprises a mixed solvent and a dispersing agent; the triacontanol raw medicine accounts for 5-30% of the total mass of the raw materials, and the mixed solvent accounts for 2.5-30% of the total mass of the raw materials.

The triacontanol suspending agent is prepared by adopting a thermal fusion polymerization method, the mass percentage of the triacontanol can reach 5-30%, the maximum 30% is more than 10 times of the content of the active ingredients of the triacontanol suspending agent product sold in the market at present, 1 ton of the triacontanol suspending agent with the mass percentage of 30% can replace at least 10 tons of the product sold in the market to prevent and treat crops with the same area, the pollution to the environment in the pesticide using process can be effectively reduced, the consumption of auxiliary materials on production raw materials can be greatly reduced, the production cost is further effectively reduced, the occupied area of the stock is reduced, and the packaging and storage cost is reduced. In a word, the triacontanol suspending agent can save resources, reduce cost and is environment-friendly.

Further, the mixed flux accounts for 2.5-15% of the total mass of the raw materials. Further, the mixed solvent is one or any combination of stearic acid, polyethylene glycol and poloxamer. The mixed solvent and triacontanol are simultaneously melted in the thermal fusion polymerization method to form a mixed condensate, so that the stability of the triacontanol suspending agent can be improved. 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.

The dispersing agent can improve the dispersion stability of triacontanol particles in water as a dispersing medium, and in the suspending agent, the dispersing agent is adsorbed on the surfaces of pesticide particles, reduces the interfacial energy of the particles, and provides electrostatic repulsion and steric hindrance to stabilize the suspending agent. Further, the dispersant accounts for 3-7% of the total mass of the raw materials. Further, the dispersing agent is one or any combination of a phosphate dispersing agent, a sulfate dispersing agent and a polycarboxylate dispersing agent; the phosphate dispersant is one or any combination of a YUS-FS3000 dispersant and a YUS-FS3300 dispersant; the sulfate dispersant is a YUS-FS7PG dispersant; the polycarboxylate dispersant is one or any combination of a YUS-CH7000 dispersant and a YUS-CS300M dispersant.

Further, the mass ratio of the triacontanol original drug to the dispersing agent is 1.5-2.5:1, for example, 2:1.

In order to improve the wettability of the triacontanol particles by the dispersion medium-water, the auxiliary agent further comprises a wetting agent. The wetting agent accounts for 0.5 to 2 percent of the total mass of the raw materials, for example, 0.5 to 1 percent; the wetting agent is sulfonate wetting agent; the sulfonate wetting agent is one or any combination of a YUS-A41B wetting agent and a YUS-A51G wetting agent.

Further, the auxiliary agent also comprises a thickening agent. In the processing of aqueous suspensions, thickeners are typically added to increase the viscosity of the system, prevent the triacontanol particles from settling and agglomerating due to gravity, act as a suspending aid, and stabilize the storage stability of the triacontanol suspensions. For the pesticide water suspending agent, if the viscosity is too low, precipitation and water separation are easy to occur, so that the stability is low, and the use is affected; if the viscosity is too high, the fluidity is poor, the dispersion effect is poor, the pasting is easy, and the processing and the use are inconvenient. In order to obtain the triacontanol suspending agent with better performance and convenient processing, preferably, the thickening agent accounts for 0.04-1% of the total mass of the raw materials, for example, 0.2-1%; the thickener is one or any combination of magnesium aluminum silicate and diutan. When the thickener contains diutan, partial water is prepared into diutan water solution before the diutan is added, and then the diutan water solution is added into the system. The mass concentration of the diutan aqueous solution is preferably 2%.

Further, the auxiliary agent also comprises an antifoaming agent. The defoamer can effectively eliminate foam generated in the production process. Further, the defoamer accounts for 0.1 to 0.5 percent of the total mass of the raw materials. The defoamer is preferably a silicone defoamer. For example, the silicone defoamer is AF1501 defoamer.

When the suspending agent is produced, stored and used in a low temperature environment, an antifreezing agent must be added to improve the stability of the suspending agent at low temperatures. The antifreezing agent changes the freezing temperature and other properties of the suspension system, so that the antifreezing capability of the suspension agent is better. In order to improve the low-temperature stability of the suspending agent, the auxiliary agent further comprises an antifreezing agent. The antifreezing agent accounts for 3-5% of the total mass of the raw materials. The antifreezing agent has good antifreezing performance and low volatility, and the lower the dissolution of the effective components is, the better. Preferably, the antifreezing agent is one or any combination of ethylene glycol and propylene glycol.

In order to prevent deterioration of the suspending agent during storage, the auxiliary agent further comprises a preservative. The preservative accounts for 0.1 to 0.5 percent of the total mass of the raw materials. The preservative is preferably pinus koraiensis.

Further, the auxiliary agent consists of a mixed solvent, a dispersing agent, a wetting agent, a thickening agent, a defoaming agent, an antifreezing agent and a preservative; the mixed flux accounts for 2.5-15% of the total mass of the raw materials, the dispersing agent 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 thickening agent accounts for 0.2-1% 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 antifreezing 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. Further, the mixed solvent accounts for 2.5 to 15 percent of the total mass of the raw materials, the dispersing agent accounts for 3 to 7 percent of the total mass of the raw materials, the wetting agent accounts for 0.5 to 1 percent of the total mass of the raw materials, the thickening agent accounts for 0.54 to 1 percent of the total mass of the raw materials, the defoaming agent accounts for 0.1 to 0.5 percent of the total mass of the raw materials, the antifreezing agent accounts for 3 to 5 percent of the total mass of the raw materials, and the preservative accounts for 0.1 to 0.5 percent of the total mass of the raw materials.

Further, the preparation method of the triacontanol suspending agent comprises the following steps: dripping the melt of the triacontanol raw material and the mixed solvent which are uniformly mixed into the water phase under the shearing action to solidify and solidify, and continuously shearing after the dripping is finished to obtain a sheared material; grinding the sheared materials, and then adding a thickening agent and a preservative for uniform mixing; the water phase consists of dispersing agent, wetting agent, antifreezing agent, defoaming agent and water. The melt is dripped into the water phase to directly undergo recrystallization and solidification, an oil-in-water suspension system is formed after dispersion, the raw material particles are further depolymerized through grinding, the raw material particles are dispersed smaller, the macromolecular dispersing agent replaces a mixed solvent or a wetting agent to fully modify the particles, and finally a thickening agent and a preservative are added to be uniformly mixed to form a relatively stable suspension system.

Further, the melt is formed by uniformly mixing the triacontanol raw material and the mixed solvent from solid state to liquid state at a temperature higher than the melting point of the triacontanol raw material. It is understood that the melting point of the flux is not higher than that of the triacontanol prodrug.

Further, the rate of the shearing action is controlled to be 9500r/min-10000r/min, and the temperature of the system is controlled to be below 30 ℃ in the shearing process. And continuing shearing for 20-25 min after the dripping is finished. The rate of continued shearing is 9500r/min-10000r/min.

Further, the grinding is sanding. The mass ratio of the shearing materials to the grinding medium is controlled to be 1:1-1.2, for example, 1:1.5 or 1:1.2 during grinding. The grinding is sanding and the grinding medium is zirconia beads having a diameter of 1.0 to 2.0 μm, for example zirconia beads having a diameter of 1.8 μm.

In the present invention, triacontanol refers to triacontanol-1.

Drawings

FIG. 1 is a graph showing the particle size distribution of sheared materials obtained during the preparation of triacontanol suspension in examples 1 to 3 and comparative example;

FIG. 2 is a graph showing particle size distribution of triacontanol suspensions in examples 1 to 3 and comparative examples;

FIG. 3 is a photograph showing evaluation of storage physical stability of triacontanol suspensions in examples 1 to 3 and comparative example, wherein 3a is a photograph showing storage at normal temperature for 60 days, 3b is a photograph showing heat storage at 54℃for 14 days, and 3c is a photograph showing storage at 0℃for 7 days;

FIG. 4 is a graph showing particle size distribution of sheared materials obtained during preparation of triacontanol suspension agent in examples 1, 4-7;

FIG. 5 is a graph showing particle size distribution of triacontanol suspensions of examples 1 and 4 to 7;

FIG. 6 is a photograph showing evaluation of storage physical stability of triacontanol suspensions in examples 4 to 7, wherein 6a is a photograph of storing at normal temperature for 60 days, 6b is a photograph of heat-storing at 54℃for 14 days, and 6c is a photograph of storing at 0℃for 7 days.

Detailed Description

The technical scheme of the invention is further described below with reference to the specific embodiments.

The triacontanol stock used in the following examples was purchased from san Jose Biotechnology Co., huzhou, 90% pure; polyethylene glycol 2000, polyethylene glycol 4000, polyethylene glycol 6000, ethylene glycol and propylene glycol, all purchased from Tianjin Gnaphalic chemical reagent and all are reagent pure; stearic acid was purchased from wuhanfengtai wilford technologies limited; poloxamer (a high molecular nonionic surfactant having an average molecular weight of 8350) was purchased from the sea-safe petrochemical plant of Jiangsu province 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 available from Shanghai Jie chemical company, inc.; magnesium aluminum silicate was purchased from Shanghai health super biotechnology Co., ltd; diutan was purchased from Hebei Lihua biotechnology limited; AF1501 (silicone defoamer) was purchased from Guangzhou chemical Co., ltd; kathon was purchased from Shandong Xiangxin chemical Co. The water used in the examples below was deionized water.

The high shear emulsifying machine used in the following examples was an A-25 laboratory high shear emulsifying machine (Shanghai European river mechanical equipments Co., ltd.) and the sand mill used was an SM-0.2L laboratory sand mill (belonging to the vertical sand mill, jiangyin city Zhuo Ying drying engineering Co., ltd.).

Examples 1 to 19

The triacontanol suspensions of examples 1 to 19 were each prepared by a thermal fusion polymerization process using the following raw materials: triacontanol original medicine, a mixed solvent, a dispersing agent and deionized water; the preparation method of the triacontanol suspending agent of examples 1 to 19 comprises the following steps:

1) Melting triacontanol raw material and a mixed solvent at 95 ℃, and uniformly stirring to obtain molten slurry;

mixing deionized water and a dispersing agent, and uniformly stirring to obtain a water phase;

2) Transferring the water phase into a high-shear emulsifying machine, switching on water phase circulating cooling water, slowly dripping molten slurry into the water phase under high-speed shearing, and continuously shearing for 25min after dripping is finished to obtain sheared materials; controlling the shearing rate to 10000r/min in the process of dripping molten slurry and the continuous shearing process after dripping, and maintaining the temperature of the system to be lower than 30 ℃;

3) Transferring the sheared materials into a grinding cylinder of a sand mill, adding grinding media (the grinding media are zirconia beads with the diameter of 1.8 mu m) according to the mass of the materials, wherein the mass of the grinding media is 1:1.2, maintaining the rotating speed of 1400r/min, and grinding for 2 hours to obtain the triacontanol suspending agent.

In examples 1 to 11, the percentage of triacontanol raw material, the mixed flux, the dispersing agent and the water in the total mass of the raw materials in each example are shown in Table 1, and the mixed flux and the dispersing agent adopted in each example are also shown in Table 1.

In examples 12 to 19, the percentage of triacontanol raw material, the solvent mixture, the dispersant and water in the total mass of the raw materials in each example was shown in Table 1, and the solvent mixture and the dispersant used in each example are also shown in Table 2.

TABLE 1 percentage (%) of triacontanol original drug, flux, dispersant and water to total mass of raw materials in examples 1 to 11, and flux and dispersant specifically used in examples 1 to 11

TABLE 2 percentage of triacontanol original drug, mixed flux, dispersant and Water to total mass of raw materials in examples 12 to 19, and Mixed flux and dispersant specifically used in examples 12 to 19

Examples 20 to 27

The triacontanol suspensions of examples 20 to 27 were each prepared by a thermal fusion polymerization process using the following raw materials: triacontanol original medicine, a mixed solvent, a dispersing agent, a wetting agent and deionized water; the preparation method of the triacontanol suspending agent of examples 20 to 27 comprises the following steps:

1) Melting triacontanol raw material and a cosolvent at 95 ℃, and uniformly stirring to obtain molten slurry;

mixing deionized water, a dispersing agent and a wetting agent, and uniformly stirring to obtain a water phase;

2) Transferring the water phase into a high-speed shearing emulsifying machine, switching on water phase circulating cooling water, slowly dripping molten slurry into the water phase under high-speed shearing, and continuously shearing for 25min after dripping is finished to obtain sheared materials; controlling the shearing rate to 10000r/min in the process of dripping molten slurry and the continuous shearing process after dripping, and maintaining the temperature of the system to be lower than 30 ℃;

3) Transferring the sheared materials to a grinding cylinder of a sand mill, adding grinding media (the grinding media are zirconia beads with the diameter of 1.8 mu m) according to the mass of the materials, wherein the mass of the grinding media is 1:1.2, maintaining the rotating speed at 1400r/min, and grinding for 2 hours to obtain the triacontanol suspending agent.

The ratio of triacontanol original drug, mixed flux, dispersant, wetting agent and water to the total mass of the raw materials in examples 20 to 27 is shown in Table 3.

TABLE 3 ratio of triacontanol Protock, mixed flux, dispersant, wetting agent and Water to total mass of raw materials in examples 20-27, and specific use of Mixed flux, dispersant and wetting agent

Examples 28 to 35

The triacontanol suspensions of examples 28 to 35 were each prepared by a thermal fusion polymerization process using the following raw materials: triacontanol original medicine, a mixed solvent, a dispersing agent, a wetting agent, a thickening agent and deionized water.

The preparation method of the triacontanol suspending agent of the embodiments 28 to 30 comprises the following steps:

adding partial deionized water into the diutan to dissolve, so as to obtain a diutan solution with the diutan concentration of 2%;

mixing the rest deionized water, the dispersing agent and the wetting agent, and uniformly stirring to obtain a water phase;

3) Transferring the sheared materials to a grinding cylinder of a sand mill, adding grinding media (the grinding media are zirconia beads with the diameter of 1.8 mu m) according to the mass of the materials, wherein the mass of the grinding media is 1:1.2, and maintaining the rotating speed of 1400r/min and sanding for 2 hours;

4) And (3) adding a thickening agent into the sanded slurry according to a proportion, and stirring for 30min at a stirring rate of 500r/min to obtain the triacontanol suspending agent.

The preparation method of the triacontanol suspending agent of examples 31 to 33 comprises the following steps:

The preparation method of the triacontanol suspending agent of the examples 34 to 35 comprises the following steps:

4) Adding diutan solution and magnesium aluminum silicate into the sanded slurry according to a proportion, and stirring for 30min at a stirring rate of 500r/min to obtain the triacontanol suspending agent.

The triacontanol original drug, the mixed solvent, the dispersing agent, the wetting agent, the thickening agent and the water adopted in examples 28 to 35 account for the total mass of the raw materials, and the mixed solvent, the dispersing agent, the wetting agent and the thickening agent adopted in the examples are shown in Table 4.

TABLE 4 triacontanol master batch, flux, dispersant, wetting agent, thickener and water used in examples 28 to 35 were the percentage of total mass of the master batch, and the flux, dispersant, wetting agent and thickener specifically used therein

Examples 36 to 51

The triacontanol suspensions of examples 36 to 51 were each prepared by a thermal fusion polymerization process using the following raw materials: triacontanol original medicine, a mixed flux, a dispersing agent, a wetting agent, a thickening agent, a defoaming agent, an antifreezing agent, a preservative and deionized water; the preparation method of the triacontanol suspending agent of the embodiments 36 to 45 and 48 to 51 comprises the following steps:

1) Melting triacontanol raw material and a cosolvent at 95 ℃, and uniformly stirring to obtain molten slurry for later use;

mixing the rest deionized water, a dispersing agent, a wetting agent, an antifreezing agent and a defoaming agent, and uniformly stirring to obtain a water phase;

3) Transferring the sheared materials to a grinding cylinder, adding grinding media (the grinding media are zirconia beads with the diameter of 1.8 mu m) according to the mass of the materials, wherein the mass of the grinding media is 1:1.2, and maintaining the rotating speed of 1400r/min and grinding for 2h;

4) Adding diutan solution, magnesium aluminum silicate and preservative into the sanded slurry according to the proportion, and stirring for 30min at the stirring rate of 500r/min to finish the processing.

The method for preparing the triacontanol suspension of example 46 comprises the steps of:

4) Adding diutan solution and preservative into the sanded slurry according to a proportion, and stirring for 30min at a stirring rate of 500r/min to finish the processing.

The method for preparing the triacontanol suspension of example 47 comprises the steps of:

4) Adding magnesium aluminum silicate and preservative into the sanded slurry according to a proportion, and stirring for 30min at a stirring rate of 500r/min to finish the processing.

The triacontanol original drug, the mixed flux, the dispersing agent, the wetting agent, the thickening agent, the antifoaming agent, the antifreezing agent, the preservative and the water adopted in examples 36 to 51 account for the total mass of the raw materials, and the mixed flux, the dispersing agent, the wetting agent, the antifoaming agent, the antifreezing agent and the preservative adopted in the examples are shown in tables 5 and 6.

TABLE 5 triacontanol master batch, flux, dispersant, wetting agent, thickener, defoamer, antifreeze, preservative and water used in examples 36 to 43 are the total mass percent of the materials and the flux, dispersant, wetting agent, thickener, defoamer, antifreeze and preservative are specifically used therein

TABLE 6 triacontanol master batch, flux, dispersant, wetting agent, thickener, defoamer, antifreeze, preservative and water used in examples 44 to 51 were the total mass percent of the materials and the fluxes, dispersant, wetting agent, thickener, defoamer, antifreeze and preservative were specifically used

Comparative example

The triacontanol suspending agent of the comparative example is prepared from the following raw materials: triacontanol original medicine, a dispersing agent and deionized water; the adopted dispersing agent is triacontanol original drug, the mass ratio of the dispersing agent to deionized water is 5:3:92; the dispersant used was YIS-FS 3000. The preparation method of the triacontanol suspending agent comprises the following steps:

1) Melting triacontanol raw material at 95 ℃ to obtain molten slurry;

3) Transferring the sheared materials into a grinding cylinder of a sand mill, adding grinding media (the grinding media are zirconia beads with the diameter of 1.8 mu m) according to the mass of the materials, wherein the mass of the grinding media is 1:1.2, maintaining the rotating speed at 1400r/min, and grinding for 2 hours to obtain the triacontanol suspending agent.

In the following experimental examples:

1) The particle size distribution was measured by using a BT-9300ST laser particle size distribution instrument (Dendong Baite instruments Co., ltd.) with reference to the laser particle size method in NY/T1860.32; the measurement is repeated 3 times to obtain an average value, and it is generally required that the D90 particle size of the suspending agent is 10 μm or less.

2) The heat storage stability is carried out according to the method in GB/T19136, about 30mL of the suspending agent sample is injected into a clean ampoule bottle (avoiding the bottleneck of sample contact) by a syringe, the ampoule bottle is sealed by high-temperature flame (avoiding solvent volatilization), the ampoule bottle is stored for 14d at the temperature of (54+/-2), and then the ampoule bottle is placed at room temperature for recovery, and after the temperature is recovered, whether the appearance changes, the fluidity is good, whether water is separated or not is observed. The appearance is required to be unchanged, the fluidity is good, the water separation rate is lower than 5 percent, the qualified sample is selected to test the content of the effective components, and the decomposition rate of the effective components is calculated. The decomposition rate of the effective components after heat storage is lower than 5 percent, which is qualified.

Wherein:

W ₀ the content (%) of the effective components measured by reserving the sample at normal temperature;

W ₁ the content (%) of the effective components measured after the sample is thermally stored.

The water evolution rate after 14d of storage at (54.+ -. 2) ℃ was calculated according to the following formula:

wherein:

h ₀ the initial liquid level of the suspension sample before heat storage to the bottom height (cm);

h ₁ the height (cm) of a water layer of a suspension sample after heat storage;

3) Measuring viscosity by using an NDJ-8S rotary viscometer (Shanghai right instrument Co., ltd.) according to the method in NY/T1860.21; and (3) selecting a No. 2 rotor for measuring the viscosity value of the suspending agent, fixing the suspending agent to be measured at the rotating speed of 30r/min, enabling the rotor not to touch the wall in the measuring process, repeatedly measuring for 3 times, and taking an average value. The viscosity was not more than 800 mPas.

4) The pH measurement was carried out according to the method in GB/T1601; the instrument was calibrated with a standard buffer solution before measurement, and the cleaned electrode was inserted into a diluted sample solution (dilution factor 100), and its pH was measured. Repeat 3 times and take the average. The pH value is 5.0-8.0.

5) Pourability is carried out in accordance with the method in GB/T31737; and judging that the pourability of the sample is qualified by taking the residue after the sample is poured is less than 5% and the residue after the washing is less than 0.5% as a standard.

(1) Pourable residue determination

The mass of the measuring cylinder is weighed, the sample is added to the position of a scale mark of 80% of the total volume of the measuring cylinder, a cover is covered, and then the measuring cylinder is weighed. Standing for 24h at room temperature, rotating the measuring cylinder from the upright position by 135 degrees, pouring for 60s, inverting for 60s, and re-weighing the mass of the measuring cylinder.

Calculate the residue after the sample was poured.

Wherein:

M ₀ the mass (g) of the cylinder with the plug;

M ₁ the sum (g) of the mass of the sample and the mass of the cylinder with the plug;

M ₂ the sum (g) of the mass of the residue after pouring and the mass of the cylinder with the stopper;

(2) post-wash residue assay

Distilled water is added to the position of a scale mark of 80% of the total volume of the measuring cylinder, a cover is covered, and the measuring cylinder is turned upside down for 10 times (2 s each time) by taking the middle part of the measuring cylinder as the center at 180 degrees. The cylinder was rotated 135 ° from the upright position, poured for 60s, inverted for 60s, and the cylinder mass was re-weighed. The residue after sample washing was calculated.

Wherein:

M ₀ the mass (g) of the cylinder with the plug;

M ₃ the sum (g) of the mass of the residue after washing and the mass of the cylinder with plug.

6) Persistent foaming is carried out in accordance with the method described in GB/T28137. Adding standard hard water into a 250mL measuring cylinder to a position of 180mL scale marks, placing the measuring cylinder on a balance, weighing 1.0g of sample, adding hard water to a position of 9cm scale marks at the bottom of a measuring cylinder plug, covering the measuring cylinder plug, and reversing for 30 times (2 s each time) at 180 degrees up and down by taking the middle of the measuring cylinder as the center. Vertically placing on a test bed, and standing. The foam volume at 1 min.+ -. 10s was recorded and repeated three times, and the average was taken as a measurement of the permanent foamability of the sample. And the persistent foamability is less than 60mL and is qualified.

7) The suspension rate measurement was carried out according to the method described in GB/T14825. Weighing a proper amount of sample in a 250mL measuring cylinder, adding standard hard water to fill up to a scale, continuously reversing for 30 times, opening a plug, vertically placing in a constant-temperature water bath kettle at 30 ℃ for standing for 30min, removing 9/10 (namely 225 mL) of suspension of the content within 10-15s by using a suction pipe, measuring the mass of the effective components in the sample and the suspension at the lower layer 1/10 (namely 25 mL) of the measuring cylinder according to a specified method, and calculating the suspension rate. The suspension rate is more than 90 percent and is qualified.

Wherein:

m ₀ preparing the mass (g) of the effective components in a sample taken from the suspension;

m ₁ the mass (g) of the active ingredient in the 1/10 suspension remained at the bottom;

and (5) converting the coefficient.

And (3) measuring the content of active ingredients:

preparing a standard sample: weighing 0.02g (accurate to 0.0002 g) of triacontanol standard substance, putting into a 100mL volumetric flask, completely dissolving with chloroform, accurately adding 1mL of internal standard solution, dissolving with chloroform, diluting to scale, and shaking.

Sample preparation: weighing 0.3g (accurate to 0.0002 g) of the sample, placing the sample in a 100mL beaker, baking the sample in an oven at 55 ℃ until the sample is nearly dry (free of moisture), cooling the sample to room temperature, accurately adding 24mL of chloroform for ultrasound, accurately adding 1mL of internal standard solution, performing ultrasound, and shaking the sample uniformly.

And (3) measuring: under the set chromatographic condition, after the instrument baseline is stable, continuously injecting a plurality of needles of standard sample solution, calculating the relative response value of each needle, and carrying out gas chromatographic analysis according to the following sequence when the relative deviation of peak areas of two adjacent needles of triacontanol and an internal standard is less than 1.0 percent: standard sample solution, and standard sample solution.

The peak areas of the triacontanol in the two-needle sample solution and the two-needle standard sample solution are respectively averaged, and the mass fraction of the triacontanol in the sample is calculated according to the following formula:

wherein:

r ₁ -an average value of the ratio of the triacontanol peak area to the internal standard peak area in the standard sample solution;

r ₂ -an average value of the ratio of the triacontanol peak area to the internal standard peak area in the sample solution;

m ₁ -the mass (g) of triacontanol;

m ₂ -mass (g) of the sample;

p-mass fraction (%) of triacontanol in the standard sample.

8) The low temperature stability is carried out in accordance with the method described in GB/T19137. About 30mL of the suspending agent sample is injected into a clean ampoule bottle (the bottleneck of the sample is avoided) by a syringe, the ampoule bottle is sealed by high-temperature flame (the solvent volatilization is avoided), the ampoule bottle is stored for 7d at the temperature of (0+/-2), then the ampoule bottle is restored at room temperature, and whether the appearance changes, the fluidity is good, whether water is separated or not is observed after the ampoule bottle is restored at room temperature. The appearance is required to be unchanged, the fluidity is good, and the water separation rate is required to be lower than 5 percent.

Experimental example 1

The particle size distribution of the sheared materials, the particle size distribution of the triacontanol suspension obtained after sanding, and the heat storage stability of the triacontanol suspension were tested in the preparation methods of the triacontanol suspensions of examples 1 to 7 and comparative examples, respectively, and the results are shown in fig. 7 and fig. 1 to 6.

TABLE 7 variation of particle size of sheared materials and suspending agents and thermal storage stability of suspending agents

Comparing the data of examples 1-3 and comparative example in Table 7, and referring to FIGS. 1-3, it can be seen that the amount of the flux mixture has a large effect on the particle size distribution during the processing of the suspending agent; wherein, the grain diameter of the sheared materials is reduced along with the increase of the dosage of polyethylene glycol 6000, and when the mass ratio of triacontanol to polyethylene glycol 6000 is less than or equal to 1, the grain diameter distribution is not much different; however, the particle size distribution of the suspending agent of example 1 was narrower after sanding, the suspending agent of example 2 was inferior, the particle size distribution of the suspending agent of example 3 was relatively slightly broader, and the suspending agent of comparative example was worst. The addition of the mixed solvent can lead the distribution of the triacontanol small particles to be more uniform and the particle size to be smaller; the results of heat storage 14D also indicate that the triacontanol suspension of example 1 has the best stability.

The melting points of the mixed fluxes selected in examples 1 and 4-7 are below 70 ℃ (wherein the melting point of polyethylene glycol 2000 is 51.3-53.4 ℃, the melting point of polyethylene glycol 4000 is 59.3-60.1 ℃, the melting point of polyethylene glycol 6000 is 59.4-62.8, the melting point of stearic acid is 68.2-69.3 ℃, the melting point of poloxamer is 55.4-58.7 ℃) and are all lower than the melting point of triacontanol (the melting point of triacontanol is 83.5-85.5 ℃);

comparing the data of examples 1, 4-7 in Table 7 with those of FIGS. 4-6, it can be seen that the sheared materials have a larger particle size, and the particle size is greatly reduced after sanding, wherein the triacontanol suspending agent of example 1 and example 5 have a slightly different particle size distribution and a relatively narrow particle size distribution after sanding; the triacontanol suspensions of examples 4, 6 and 7 were not very different and the particle size distribution was relatively slightly broader; the heat storage results also show that the triacontanol suspending agents of examples 1 and 5 have lower water evolution rate and better stability.

Experimental example 2

The viscosity of the sheared materials and the viscosity of the triacontanol suspension obtained after sanding in the preparation methods of triacontanol suspensions of examples 8 to 15 were tested, respectively, and the results are shown in table 8.

TABLE 8 viscosity response of triacontanol suspensions of examples 8-15

Examples	Viscosity after shearing/mPa.s	Post-sanding viscosity/mPa.s	Judgment result
				8	39.6	88	Qualified product
9	215.6	385.3	Qualified product
				10	398.2	540.3	Qualified product
11	897.6	-	Failure to pass
				12	349.7	509.2	Qualified product
13	298.6	464.3	Qualified product
				14	369.5	498.2	Qualified product
15	420.8	529.1	Qualified product

"-" means creaming.

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 suspending agent, and the viscosity of the suspending agent increases significantly with the increase in drug loading; however, the viscosity after shearing is more different from the viscosity after sanding, because the ratio of the molten slurry is increased along with the increase of the drug loading, the molten slurry is difficult to shear and disperse, larger blocks are often formed, the blocks cannot be sheared, and the slurry is uniformly dispersed after sanding, so that the viscosity is increased. As is evident from the above table, example 11 was directly creamed after sanding, and examples 8 to 10 all exhibited better appearance.

From the data of examples 10, 12-15 in Table 8, it is seen that the viscosity of the triacontanol suspension decreases and then increases as the dispersant ratio increases from 3% to 7%. When the amount of the dispersant is small, the interfacial energy of the raw material can be continuously reduced, so that the viscosity is reduced with the increase of the amount of the dispersant. When the drug particles reach saturation adsorption, the amount of dispersant increases, causing vacancy flocculation and an increase in the viscosity of the system. When the proportion of the dispersing agent is 5%, the viscosity of the triacontanol suspending agent is the lowest.

Experimental example 3

The suspension ratios of the triacontanol suspensions of examples 13 to 27 were measured, respectively, and the results of the suspension ratios of the triacontanol suspensions of examples 13 to 19 are shown in Table 9, and the suspension ratios of the triacontanol suspensions of examples 20 to 27 are shown in Table 10.

TABLE 9 suspension Rate of triacontanol suspensions of examples 14 to 20

Examples	13	16	17	18	19
						Suspension rate/%	92.3	93.7	85.3	87.6	82.3

As is clear from comparison of the suspension ratios of the triacontanol suspensions of examples 13 to 19, the influence of different dispersants on the suspension ratio of the triacontanol suspension is remarkable, the suspension ratios of the suspension concentrates of the dispersants YUS-FS3000 and YUS-FS3300 are both greater than 90%, and the suspension concentrates of the dispersants YUS-FS7PG, YUS-CH7000 and YUS-CS300M are less than 90%.

Table 10 suspension ratios of triacontanol suspensions of examples 20 to 27

Examples	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

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. The synergistic or antagonistic effect is produced by molecular interactions, complexing, or electrostatic attraction, or repulsion, as well as other physical or chemical interactions. If the effect produced after mixing is better than that of the individual components, it is called synergistic effect; if the contrary is said to have an antagonistic effect.

As is clear from the comparison of the suspension ratios of the triacontanol suspensions of examples 20 to 27, when the wetting agent was YUS-A41B, the suspension ratio of the suspension was increased at 0.5%, and when the amount was increased at 1%, the suspension ratio was decreased instead; when the wetting agent is YUS-A51G, the suspension rates are reduced at 0.5% and 1%. It is thus clear that the dispersants YUS-FS3000 and YUS-FS3300, when combined with 0.5% YUS-A41B wetting agent, produce a synergistic effect that results in an increase in the suspension rate of the suspending agent.

Experimental example 4

The viscosities of the triacontanol suspensions of examples 28 to 35 were measured, respectively, and the results are shown in Table 11.

TABLE 11 viscosity of triacontanol suspensions of examples 28-35

As can be seen from Table 11, the viscosity of the single use diutan or magnesium aluminum silicate suspending agent is basically below 400 mPa.s, and the viscosity is obviously increased when the single use diutan or magnesium aluminum silicate suspending agent and the single use diutan or magnesium aluminum silicate suspending agent are compounded, wherein the combination effect of 0.08% diutan and 0.5% magnesium aluminum silicate is best, the viscosity of the suspending agent is 459.7 mPa.s, the viscosity is proper, and the fluidity of the suspending agent is good.

Experimental example 5

The low-temperature stability of the triacontanol suspensions of examples 36 to 41 was measured to determine whether they were acceptable, and the results are shown in Table 12.

TABLE 12 Low temperature stability of triacontanol suspensions of examples 36-41

Examples	36	37	38	39	40	41
							Judgment result	Failure to pass	Qualified product	Qualified product	Failure to pass	Qualified product	Qualified product

As is clear from Table 12, the use of ethylene glycol and propylene glycol in amounts of 3-5% gives good anti-freezing effect, and the suspension system is not adversely affected, and ethylene glycol is selected as the anti-freezing agent in an amount of 3% for cost saving.

Experimental example 6

The triacontanol suspensions of examples 42 to 51 were each tested for performance and the results are shown in Table 13.

TABLE 13 Performance test results of triacontanol suspensions of examples 42 to 51

As is clear from Table 13, the triacontanol suspensions of examples 42 to 51 were all acceptable in terms of each index.

Claims

1. A triacontanol suspending agent, characterized in that: the material is prepared by adopting a thermal fusion polymerization method by the following raw materials: triacontanol original medicine, auxiliary agent and water; the auxiliary agent comprises a mixed solvent and a dispersing agent; the triacontanol raw medicine accounts for 5-30% of the total mass of the raw materials, and the mixed solvent accounts for 2.5-30% of the total mass of the raw materials.

2. The triacontanol suspension according to claim 1, wherein: the mixed flux accounts for 2.5 to 15 percent of the total mass of the raw materials; the mixed solvent is one or any combination of stearic acid, polyethylene glycol and poloxamer.

3. The triacontanol suspension according to claim 1, wherein: the dispersing agent accounts for 3-7% of the total mass of the raw materials, and is one or any combination of a phosphate dispersing agent, a sulfate dispersing agent and a polycarboxylate dispersing agent.

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

5. The triacontanol suspension according to claim 1, wherein: the auxiliary agent also comprises a thickening agent, wherein the thickening agent 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 comprises an antifoaming agent, wherein the antifoaming agent accounts for 0.1-0.5% of the total mass of the raw materials; the defoaming agent is an organosilicon defoaming agent.

7. The triacontanol suspension according to claim 1, wherein: the auxiliary agent also comprises an antifreezing agent, wherein the antifreezing 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 comprises a preservative, wherein the preservative accounts for 0.1-0.5% of the total mass of the raw materials.

9. The triacontanol suspension according to any one of claims 1 to 8, wherein: the auxiliary agent consists of a mixed solvent, a dispersing agent, a wetting agent, a thickening agent, a defoaming agent, an antifreezing agent and a preservative; the mixed flux accounts for 2.5-15% of the total mass of the raw materials, the dispersing agent 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 thickening agent accounts for 0.2-1% 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 antifreezing 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 according to claim 9 wherein: the preparation method of the triacontanol suspending agent comprises the following steps: dripping the melt of the triacontanol raw material and the mixed solvent which are uniformly mixed into the water phase under the shearing action to solidify and solidify, and continuously shearing after the dripping is finished to obtain a sheared material; grinding the sheared materials, and then adding a thickening agent and a preservative for uniform mixing; the water phase consists of dispersing agent, wetting agent, antifreezing agent, defoaming agent and water.