Triacontanol microemulsion and preparation method thereof

Abstract

The invention discloses a triacontanol microemulsion and a preparation method thereof, and relates to the technical field of medicament preparation. The triacontanol microemulsion is prepared from the following components in percentage by mass: 0.1% of triacontanol active compound, 10-30% of emulsifier, 2-7% of oleophylic regulator and the balance of water, wherein the emulsifier takes fatty alcohol-polyoxyethylene ether with an HLB (Hydrophile-Lipophile Balance) value not less than 13 as a main emulsifier; the oleophylic regulator is an ester environment-friendly solvent with a dielectric constant less than 5. According to the invention, the triacontanol is not dissolved in a solvent, and only a small amount of oleophylic regulator is added to adjust the hydrophilic-oleophylic balance of the system, so that the triacontanol has good stability in the system, the formula is green and environment-friendly, the preparation process is simple, the energy consumption is low, and the method is suitable for large-scale production.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparation, and in particular to a triacontanol microemulsion and a preparation method thereof. Background Art

[0002] Triacontanol (TRIA) is a long-chain fatty alcohol composed of 30 carbon atoms, with the chemical formula CH3(CH2). 28 CH2OH, which is widely present in nature, is an important component of wax deposited on the protective layer of plant leaves, stems, flowers, fruits and seeds. It is also a naturally occurring plant growth regulator. Triacontanol can promote seed germination, promote the division and elongation of plant cells, promote flower bud differentiation, increase the number of flowering, increase fruiting rate and thousand-grain weight, delay leaf senescence, promote early maturity of crops, improve quality and many other physiological effects. It has a significant yield-increasing effect on many crops such as tomatoes, cucumbers, lettuce, corn, and rice. Triacontanol is a white flaky crystal with a melting point of 85.5-86.5℃. It is insoluble in water, difficult to dissolve in cold methanol, ethanol, and acetone, and easily soluble in organic solvents such as ether, chloroform, and carbon tetrachloride.

[0003] At present, the monomer dosage form of drug registration is microemulsion, and the compound dosage forms include suspension, soluble powder, wettable powder, emulsion, water dispersible granule, emulsifiable concentrate and water emulsion. Previous studies have confirmed (Zeng Dongmei, 2018): the use effect of microemulsion obtained by microemulsification of triacontanol is better than that of solid preparations, water emulsions and suspensions. Therefore, microemulsification of triacontanol into microemulsions is a research focus in the industry. Due to the special physical and chemical properties of triacontanol, it is often completely dissolved in ethanol and other strong polar organic solvents in production, and then emulsified at high temperature with emulsifiers to obtain the desired microemulsion. However, due to its solubility limitation, triacontanol has many problems in production and use, such as poor dispersion and easy emulsion precipitation; in addition, emulsification at high temperature consumes a lot of energy in actual production, making it difficult to control the production cost of production enterprises. In order to solve these problems, people have conducted research from different directions. Some have modified the structure of triacontanol. For example, the patent application document with publication number CN1078851A discloses a treatment scheme for improving the water solubility of triacontanol by inclusion of triacontanol with cyclodextrin; and the patent application document with publication number CN107998403A connects PEG and triacontanol by covalent bonds through easily degradable ester bonds to obtain water-soluble prodrugs of triacontanol, thereby making various water-soluble preparations; there are also preparations that add substances that are easily soluble in triacontanol as cosolvents. For example, the patent application document with publication number CN115624027A discloses a technical scheme for using triacontanol to be configured into an aqueous emulsion using organic solvents such as cosolvents and antifreeze agents, wherein the cosolvent is one or more of dimethyl sulfoxide, solvent oil S-150#, N-methylpyrrolidone, n-octanol, cyclohexanone or N,N-dimethylacetamide. However, the method of improving the water solubility of triacontanol by structural modification of triacontanol is relatively complicated, difficult to implement, and costly, and the change in structure may affect its use effect; and the cosolvent added in the patent application document with publication number CN115624027A has certain toxicity, making the prepared microemulsion a non-environmentally friendly preparation with toxicity or irritation. Therefore, the development of a safe and environmentally friendly triacontanol microemulsion with simple process, low energy consumption and stable quality is of great significance to the efficient application of triacontanol. Summary of the invention

[0004] The invention provides a triacontanol microemulsion and a preparation method thereof, so as to solve the technical problems of high preparation cost, environmental pollution and unstable quality of the existing triacontanol microemulsion.

[0005] The technical solution adopted by the present invention is as follows:

[0006] A triacontanol microemulsion is composed of the following components in percentage by mass: 0.1% of triacontanol original drug, 10-30% of emulsifier, 2-7% of lipophilic regulator, and the balance of water; wherein the emulsifier is mainly a fatty alcohol polyoxyethylene ether with an HLB value of not less than 13; and the lipophilic regulator is an ester environmentally friendly solvent with a dielectric constant of less than 5.

[0007] Preferably, the emulsifier also uses alkylphenol polyoxyethylene ether TX-15 as an auxiliary emulsifier, and the mass ratio of the main emulsifier to the auxiliary emulsifier is 7 to 13:1.

[0008] More preferably, the mass ratio of the primary emulsifier to the auxiliary emulsifier is 9 to 11:1.

[0009] Preferably, the mass percentage of the emulsifier in the triacontanol microemulsion is 17-25%.

[0010] More preferably, the mass percentage of the emulsifier in the triacontanol microemulsion is 18-20%.

[0011] Preferably, the lipophilic regulator is one or more of soybean oil, sesame oil, peanut oil, sunflower oil, castor oil, fatty acid methyl ester, methyl oleate, and ethyl oleate.

[0012] Preferably, the mass percentage of the lipophilic regulator in the triacontanol microemulsion is 3-6%.

[0013] The preparation method of the triacontanol microemulsion comprises the following steps: mixing the triacontanol, emulsifier, lipophilic regulator and water not less than the amount of the emulsifier in the formula, heating to 90°C and stirring, stopping heating and keeping stirring when the mixture is stirred to a clear and transparent state, then adding the remaining water in the formula under stirring, continuing to stir until it is clear and transparent, and obtaining the triacontanol microemulsion when the temperature drops to room temperature.

[0014] Furthermore, the mass ratio of water to emulsifier added for the first time is 1-1.5:1.

[0015] Furthermore, the mass ratio of water to emulsifier added for the first time is 1-1.2:1.

[0016] In summary, compared with the prior art, the present invention has the following advantages and beneficial effects:

[0017] 1. The present invention does not use a solvent to dissolve triacontanol, but only adds a small amount of lipophilic regulator to adjust the hydrophilic-lipophilic balance of the system, so that triacontanol has good stability in the system;

[0018] 2. The lipophilic regulator used in the present invention has the advantages of low toxicity and environmental protection;

[0019] 3. The process of preparing triacontanol microemulsion of the present invention is relatively simple. Only the triacontanol original drug, emulsifier, lipophilic regulator and part of water are heated, and the remaining water is added at room temperature to obtain a qualified microemulsion, which improves the preparation content and quality stability, reduces production energy consumption, and also reduces the preparation cost, meeting the requirements of green production. DETAILED DESCRIPTION

[0020] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with various embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention, that is, the embodiments described are only part of the embodiments of the present invention, rather than all of the embodiments.

[0021] The word "embodiment" used here as an "exemplary" does not necessarily mean that any embodiment described is superior to or better than other embodiments. Unless otherwise specified, the performance index tests in the embodiments of this method adopt conventional test methods in the art. The terms described in the present invention are only for describing specific implementation methods and are not intended to limit the content disclosed in the present invention.

[0022] Unless otherwise specified, the technical and scientific terms used herein have the same meanings as commonly understood by ordinary technicians in the technical field to which the invention belongs; other raw materials, reagents, experimental methods and technical means not specifically specified in the present invention refer to the raw materials and reagents commonly used by ordinary technicians in the field, as well as the commonly used experimental methods and technical means.

[0023] The triacontanol microemulsion provided by the present invention comprises 0.1% of triacontanol original drug, 10-30% of emulsifier, 2-7% of lipophilic regulator, and the balance is water; wherein the emulsifier comprises a main emulsifier or a main emulsifier / co-emulsifier, the main emulsifier is a fatty alcohol polyoxyethylene ether with an HLB value of not less than 13, the co-emulsifier is an alkylphenol polyoxyethylene ether, and the ratio of the main emulsifier to the co-emulsifier is 7-13:1, more preferably 9-11:1. The total amount of the emulsifier is 10-30%, preferably 17-25%, more preferably 18-20%. The lipophilic regulator is an ester environmentally friendly solvent with a dielectric constant of less than 5, specifically including one or more of soybean oil, sesame oil, peanut oil, sunflower seed oil, castor oil, fatty acid methyl ester, methyl oleate, ethyl oleate, etc., and the dosage is 2-7%, preferably 3-6%. The preparation process comprises the following steps: mixing triacontanol, an emulsifier, a lipophilic regulator and water not less than the amount of the emulsifier in the formula, heating to 90°C and stirring, stopping heating and maintaining stirring when the mixture is stirred to a clear and transparent state, then adding the remaining water in the formula under stirring, continuing to stir until it becomes clear and transparent, and obtaining a triacontanol microemulsion when the temperature drops to room temperature.

[0024] The present invention is further described below in conjunction with various embodiments.

[0025] Example 1

[0026] This example explores the effect of solvents of different polarities as lipophilic regulators on triacontanol microemulsions, and specifically uses 0.1% triacontanol, 20% fatty alcohol polyoxyethylene ether AEO-9 emulsifier, 3% lipophilic regulator, and the balance water as the basic formula for the test. All components are weighed in proportion and mixed evenly, heated to boiling, and the evaporated water is supplemented after cooling. The experimental design is shown in Table 1.

[0027] Table 1 Information on lipophilic modifiers of different polarities

[0028]

[0029]

[0030] For each treatment, the state of the preparation during mixing and heating, and the state of the preparation after cooling were observed. An appropriate amount of the preparation was put into an ampoule, sealed, and placed at 4°C and 54°C to observe the low temperature and hot storage stability. The results are shown in Table 2.

[0031] Table 2 Test results of lipophilic regulators with different polarities

[0032] Processing number Initial state After cooling 4℃14 days status 54℃ 14 days status Emulsion stability Process 1 transparent translucent milky Layering Failure Process 2 transparent translucent milky Layering Failure Process 3 transparent translucent translucent translucent qualified Process 4 transparent Separation / / Failure Process 5 transparent Separation / / Failure Process 6 transparent Separation / / Failure Process 7 transparent Separation / / Failure Process 8 Milky white paste Milky white paste / / Failure Process 9 Milky white paste Milky white paste / / Failure

[0033] From the experimental results in Table 2, non-polar solvents have good test results. They can reach a transparent state under heating and are translucent after cooling. However, xylene and kerosene showed abnormalities after 14 days of cold and hot storage. They were milky white at low temperature and stratified at high temperature. It can be seen that not all non-polar solvents can achieve ideal results. Medium-grade and strong polar solvents performed poorly. Although ethanol and other four solvents can reach a transparent state under heating conditions, triacontanol precipitates after cooling, and the performance is poor. N-methylpyrrolidone and N,N-dimethylformamide performed the worst, and no good microemulsions could be obtained under the treatment conditions. The results show that the addition of some non-polar solvents improves the stability of the microemulsion, and also shows an amazing side. It is not necessary to use solvents to dissolve all triacontanol to prepare microemulsions. At this time, the non-polar solvent may only provide lipophilicity and act as a bridge to connect the oil phase and the water phase.

[0034] Example 2

[0035] This example further explores the effect of ester solvents with different dielectric constants of dielectric constant <5 on triacontanol microemulsion when used as lipophilic regulators. Specifically, 0.1% triacontanol, 20% fatty alcohol polyoxyethylene ether AEO-9 emulsifier, 3% lipophilic regulator, and the balance water are used as the basic formula for the test. All components are weighed in proportion and mixed evenly, heated to boiling, and the evaporated water is supplemented after cooling. The experimental design is shown in Table 3.

[0036] Table 3 Information of different non-polar lipophilic regulators

[0037]

[0038]

[0039] For each treatment, the state of the preparation during mixing and heating, and the state of the preparation after cooling were observed. An appropriate amount of the preparation was put into an ampoule, sealed, and placed at 4°C and 54°C to observe the low temperature and hot storage stability. The results are shown in Table 4.

[0040] Table 4 Test results of different non-polar lipophilic regulators

[0041] Processing number Initial state After cooling 4℃14 days status 54℃ 14 days status Emulsion stability Process 1 transparent translucent Low transparency translucent qualified Process 2 transparent translucent Low transparency translucent qualified Process 3 transparent translucent translucent translucent qualified Process 4 transparent translucent translucent translucent qualified Process 5 transparent translucent translucent translucent qualified Process 6 transparent translucent translucent translucent qualified Process 7 transparent translucent translucent translucent qualified

[0042] As shown in Table 4, the microemulsions obtained from the eight groups of solvents can all be transparent in the initial state and translucent after cooling. However, after a long period of cold and hot storage, the performance is different. The low temperature performance of dimethyl carbonate and castor oil with larger dielectric constants is relatively poor, but basically within the qualified range; the rest of the treatments all perform well, among which soybean oil and fatty acid methyl ester are the best, and their transparency in cold and hot storage states is higher than that of other treatments. Subsequent experiments are conducted using soybean oil and fatty acid methyl ester as lipophilic regulators. The results of this embodiment show that ester solvents with different dielectric constants of dielectric constant <5 are generally suitable for lipophilic regulators of triacontanol microemulsions, but ester solvents with larger dielectric constants (>3.2) perform less well.

[0043] Example 3

[0044] This example explores the effect of the amount of lipophilic regulator on triacontanol microemulsion, and selects environmentally friendly solvents such as soybean oil and fatty acid methyl ester for testing, triacontanol 0.1%, fatty alcohol polyoxyethylene ether AEO-9 emulsifier 20%, lipophilic regulator 2-7%, and the balance water as the basic formula for testing. All components are weighed in proportion and mixed evenly, heated to boiling, and evaporated water is supplemented after cooling. The experimental design is shown in Table 5.

[0045] Table 5 Soybean oil and methyl oleate dosage test

[0046]

[0047]

[0048] For each treatment, the state of the preparation during mixing and heating, and the state of the preparation after cooling were observed. An appropriate amount of the preparation was put into an ampoule, sealed, and placed at 4°C and 54°C to observe the low temperature and hot storage stability. The results are shown in Table 6.

[0049] Table 6 Results of the test on the dosage of lipophilic regulator

[0050] Processing number Initial state After cooling 4℃14 days status 54℃ 14 days status Emulsion stability Process 1 transparent translucent translucent stratification, precipitation Failure Process 2 transparent translucent translucent translucent qualified Process 3 transparent translucent translucent translucent qualified Process 4 transparent translucent translucent translucent qualified Process 5 transparent translucent translucent translucent qualified Process 6 transparent translucent translucent milky Failure Process 7 transparent translucent translucent stratification, precipitation Failure Process 8 transparent translucent translucent translucent qualified Process 9 transparent translucent translucent translucent qualified Processing 10 transparent translucent translucent translucent qualified Process 11 transparent translucent translucent translucent qualified Processing 12 transparent translucent translucent milky Failure

[0051] From the results in Table 6, it can be seen that within the set range, soybean oil and fatty acid methyl ester can be transparent in the initial state, and can maintain translucency after cooling and at low temperatures. However, they are not very stable under hot storage. The overall rule is that they are relatively stable within a certain range. Too high or too low content of soybean oil and fatty acid methyl ester cannot be well stabilized. If the content is too low, hot storage will show stratification and precipitation, and if the content is too high, it will show milky white opaque. The results show that within a certain range of soybean oil and fatty acid methyl ester content, the preparation is relatively stable.

[0052] Example 4

[0053] This embodiment explores the influence of emulsifier types on triacontanol microemulsion, and tests are carried out with triacontanol 0.1%, emulsifier 20%, fatty acid methyl ester 3%, and balance water as basic formula. 10 different types of emulsifiers are set, including 2 fatty alcohol polyoxyethylene ethers, 2 alkylphenol polyoxyethylene ethers, 2 fatty alcohol polyoxyethylene esters, 2 castor oil polyoxyethylene ethers, and 2 polyethylene glycol fatty acid esters. All components are weighed in proportion and mixed evenly, heated to boiling, and evaporated water is supplemented after cooling. The experimental design is shown in Table 7.

[0054] Table 7 Emulsifier type settings

[0055]

[0056]

[0057] For each treatment, the state of the preparation during mixing and heating, and the state of the preparation after cooling were observed. An appropriate amount of the preparation was put into an ampoule, sealed, and placed at 4°C and 54°C to observe the low temperature and hot storage stability. The results are shown in Table 8.

[0058] Table 8 Emulsifier type test results

[0059] Processing number Initial state After cooling 4℃14 days status 54℃ 14 days status Emulsion stability Process 1 transparent Low transparency milky stratification, precipitation Failure Process 2 transparent translucent translucent translucent qualified Process 3 transparent Low transparency milky stratification, precipitation Failure Process 4 transparent translucent Low transparency transparent qualified Process 5 transparent milky milky stratification, precipitation Failure Process 6 transparent translucent Translucent, precipitation transparent Failure Process 7 transparent milky Transparent, precipitation translucent Failure Process 8 transparent milky Transparent, precipitation translucent Failure Process 9 transparent milky Translucent, precipitation translucent Failure Processing 10 transparent milky Translucent, precipitation translucent Failure

[0060] It can be seen from the experimental results that qualified products can be obtained when only AEO-9 and TX-15 are used as emulsifiers, and AEO-9 performs relatively balanced throughout the test and has good stability. We consider that the HLB value may affect the stability of the microemulsion, so subsequent experiments further explore fatty alcohol polyoxyethylene ether emulsifiers with similar HLB values. TX-15 performs slightly worse at low temperatures, has better transparency at high temperatures, and the original drug does not precipitate. The remaining types of emulsifiers have various abnormalities that do not meet the dosage form requirements. The results show that some emulsifiers of fatty alcohol polyoxyethylene ether and alkylphenol polyoxyethylene ether have good emulsification properties, which makes the triacontanol microemulsion have good stability.

[0061] Example 5

[0062] In order to verify whether the microemulsion prepared when the fatty alcohol polyoxyethylene ether with an HLB value of not less than 13 is used as an emulsifier has the same stability, this embodiment explores the influence of other fatty alcohol polyoxyethylene ethers with an HLB value of not less than 13 on the triacontanol microemulsion, and the experiment is carried out with 0.1% triacontanol, 20% emulsifier, 3% fatty acid methyl ester, and the balance water as the basic formula. Set 6 different types of emulsifiers, weigh all the components in proportion and mix them evenly, heat to boiling, and add evaporated water after cooling. The experimental design is shown in Table 9.

[0063] Table 9 Settings for different types of fatty alcohol polyoxyethylene ethers

[0064] Processing number type name HLB value Process 1 Lauryl alcohol polyoxyethylene ether AEO-10 13.5 Process 2 Cholesterol polyoxyethylene ether Solulan C-24 14 Process 3 Lanolin alcohol polyoxyethylene ether Solulan PB-20 14 Process 4 Oleyl alcohol polyoxyethylene ether Ameroxol OE-20 15 Process 5 Multi-branched isomeric tridecanol polyoxyethylene ether OXO1309 13.3 Process 6 Monobranched dodecanol polyoxyethylene ether Ger12E9 13.5

[0065] For each treatment, the state of the preparation during mixing and heating, and the state of the preparation after cooling were observed. An appropriate amount of the preparation was put into an ampoule, sealed, and placed at 4°C and 54°C to observe the low temperature and hot storage stability. The results are shown in Table 10.

[0066] Table 10 Test results of different types of fatty alcohol polyoxyethylene ethers

[0067] Processing number Initial state After cooling 4℃14 days status 54℃ 14 days status Emulsion stability Process 1 transparent transparent transparent transparent qualified Process 2 transparent transparent transparent transparent qualified Process 3 transparent transparent transparent transparent qualified Process 4 transparent transparent transparent transparent qualified Process 5 transparent transparent transparent transparent qualified Process 6 transparent transparent transparent transparent qualified

[0068] It is not difficult to see from the experimental results of this embodiment that the microemulsions prepared when the fatty alcohol polyoxyethylene ether with an HLB value of not less than 13 is used as an emulsifier have good stability.

[0069] Example 6

[0070] This example explores the effect of the ratio of AEO-9 and TX-15 compound emulsifiers on triacontanol microemulsion, and specifically uses 0.1% triacontanol, 20% emulsifier, 3% fatty acid methyl ester, and the balance water as the basic formula for the test. Set different ratios of primary emulsifier and auxiliary emulsifier. All components are weighed in proportion and mixed evenly, heated to boiling, and evaporated water is supplemented after cooling. The experimental design is shown in Table 11.

[0071] Table 11 Main emulsifier and auxiliary emulsifier ratio settings

[0072] Processing number AEO-9(%) TX-15(%) Proportion Process 1 18.7 1.3 15:1 Process 2 18.6 1.4 13:1 Process 3 18.3 1.7 11:1 Process 4 18 2 9:1 Process 5 17.5 2.5 7:1 Process 6 16.7 3.3 5:1

[0073] For each treatment, the state of the preparation during mixing and heating, and the state of the preparation after cooling were observed. An appropriate amount of the preparation was put into an ampoule, sealed, and placed at 4°C and 54°C to observe the low temperature and hot storage stability. The results are shown in Table 12.

[0074] Table 12 Test results of compound emulsifier dosage

[0075] Processing number AEO-9:TX-15 Initial state After cooling 4℃14 days status 54℃ 14 days status Emulsion stability Process 1 15:1 transparent transparent translucent translucent qualified Process 2 13:1 transparent transparent translucent translucent qualified Process 3 11:1 transparent transparent transparent transparent qualified Process 4 9:1 transparent transparent transparent transparent qualified Process 5 7:1 transparent transparent translucent transparent qualified Process 6 5:1 transparent translucent Low transparency transparent qualified

[0076] From the test results of 6 compounding ratios of AEO-9 and TX-15, it can be seen that when the ratio is 7-13:1, the triacontanol microemulsion has better properties, especially when the ratio is 9-11:1, the preparation state under all conditions is transparent and its stability is the best.

[0077] Example 7

[0078] The effect of the amount of AEO-9 and TX-15 compound emulsifiers on triacontanol microemulsion was discussed. Specifically, 0.1% triacontanol, 15-25% emulsifier, 3% fatty acid methyl ester, and the balance water were used as the basic formula for the experiment. Different ratios of the main emulsifier and the auxiliary emulsifier were set. All components were weighed in proportion and mixed evenly, heated to boiling, and the evaporated water was supplemented after cooling. The experimental design is shown in Table 13.

[0079] Table 13 Setting of dosage of compound emulsifier

[0080] Processing number AEO-9(%) TX-15(%) Total amount (%) Process 1 22.7 2.3 25 Process 2 20.9 2.1 23 Process 3 19.1 1.9 21 Process 4 17.3 1.7 19 Process 5 15.5 1.5 17 Process 6 13.6 1.4 15

[0081] For each treatment, the state of the preparation during mixing and heating, and the state of the preparation after cooling were observed. An appropriate amount of the preparation was put into an ampoule, sealed, and placed at 4°C and 54°C to observe the low temperature and hot storage stability. The results are shown in Table 14.

[0082] Table 14 Test results of compound emulsifier dosage

[0083] Processing number Emulsifier (%) Initial state After cooling 4℃14 days status 54℃ 14 days status Emulsion stability Process 1 25 transparent transparent transparent transparent qualified Process 2 23 transparent transparent transparent transparent qualified Process 3 21 transparent transparent transparent transparent qualified Process 4 19 transparent transparent transparent transparent qualified Process 5 17 transparent translucent translucent transparent qualified Process 6 15 transparent translucent Low transparency transparent Failure

[0084] This embodiment sets 6 concentration gradients for testing, and it is found that as the amount of emulsifier increases, the stability of the emulsion increases, and when the content exceeds 17%, the triacontanol microemulsion can be stably present. It shows that the amount of emulsifier in the triacontanol microemulsion should be above 17%, and preferably 18-20% to control the cost.

[0085] Example 8

[0086] This example explores the effects of different preparation processes on triacontanol microemulsions, and tests are conducted using 0.1% triacontanol, a ratio of 10:1 between the primary emulsifier and the auxiliary emulsifier, 20% usage, 3% fatty acid methyl ester, and the balance water as the basic formula. The configuration process is performed as shown in Table 15.

[0087] Table 15 Preparation process settings

[0088]

[0089]

[0090] For each treatment, the state of the preparation during mixing and heating, and the state of the preparation after cooling were observed. An appropriate amount of the preparation was put into an ampoule, sealed, and placed at 4°C and 54°C to observe the low temperature and hot storage stability. The results are shown in Table 16.

[0091] Table 16 Test results of different preparation processes

[0092] Process No. Initial state After cooling 4℃14 days status 54℃ 14 days status Emulsion stability Process 1 Unable to emulsify / / / Failure Craft 2 Unable to emulsify / / / Failure Craft 3 milky milky milky translucent Failure Craft 4 milky milky milky translucent Failure Craft 5 transparent transparent transparent transparent qualified

[0093] This embodiment sets 5 processes. Process 1 and process 2 have the same processing method, and the order of adding the oil phase and the water phase is exchanged. Under this process, the oil phase cannot be emulsified and a stable microemulsion cannot be formed. Process 3 and process 4 have the same processing method, and the order of adding the oil phase and the water phase is exchanged. Under this process, the oil phase can be emulsified, but a microemulsion cannot be formed. Process 5 can form a microemulsion well, and has good stability.

[0094] Example 9

[0095] This example further explores the effect of the amount of water added for the first time on the triacontanol microemulsion, and tests are conducted with 0.1% triacontanol, a ratio of 10:1 between the primary emulsifier and the auxiliary emulsifier, 20% of the amount, 3% of fatty acid methyl ester, and the balance of water as the basic formula. The configuration process is carried out according to Table 17. Triacontanol, fatty acid methyl ester, emulsifier and water are all heated together until clear and transparent, the remaining water is heated to a set temperature and kept warm, and the remaining water is added under stirring.

[0096] Table 17 Preparation process settings

[0097] Process No. Emulsifier (%) water(%) Process 1 20 0 Craft 2 20 10 Craft 3 20 20 Craft 4 20 40 Craft 5 20 60 Process 6 20 77

[0098] For each treatment, the state of the preparation during mixing and heating, and the state of the preparation after cooling were observed. An appropriate amount of the preparation was put into an ampoule, sealed, and placed at 4°C and 54°C to observe the low temperature and hot storage stability. The results are shown in Table 18.

[0099] Table 18 Test results of water added once

[0100]

[0101]

[0102] From the results, it can be seen that the initial state, the state after cooling and the low-temperature storage state of process 1 and process 2 are all milky white. Only at 54°C can the liquid reach a translucent state, and the emulsion stability is also unqualified. Transparent microemulsions can be formed at all time points of processes 3-6, and their emulsion stability is also qualified. The results show that when the amount of water added at one time is less than the amount of emulsifier, a stable microemulsion cannot be formed. Only when the amount of water added at one time is the same as the amount of emulsifier can a stable microemulsion be formed.

[0103] Example 10

[0104] This example further explores the effect of the temperature of the second water addition on the triacontanol microemulsion, and tests are conducted with 0.1% triacontanol, a ratio of 10:1 between the primary emulsifier and the auxiliary emulsifier, 20% usage, 3% fatty acid methyl ester, and the balance water as the basic formula. The configuration process is carried out according to Table 19. Triacontanol, fatty acid methyl ester, emulsifier and water are all heated together until clear and transparent, and the remaining water is added under stirring.

[0105] Table 19 Preparation process settings

[0106] Process No. Emulsifier (%) Primary water volume (%) Secondary water temperature (℃) Process 1 20 20 25 Craft 2 20 20 50 Craft 3 20 20 75 Craft 4 20 20 100

[0107] For each treatment, the state of the preparation during mixing and heating, and the state of the preparation after cooling were observed. An appropriate amount of the preparation was put into an ampoule, sealed, and placed at 4°C and 54°C to observe the low temperature and hot storage stability. The results are shown in Table 20.

[0108] Table 20 Secondary addition of water temperature test results

[0109] Process No. Secondary water temperature (℃) Initial state After cooling 4℃14 days status 54℃ 14 days status Emulsion stability Process 1 25 transparent transparent transparent transparent qualified Craft 2 50 transparent transparent transparent transparent qualified Craft 3 75 transparent transparent transparent transparent qualified Craft 4 100 transparent transparent transparent transparent qualified

[0110] From the results, it can be seen that the preparations under the four water temperature conditions are all transparent and the emulsion stability is qualified. The results show that the triacontanol microemulsion is not sensitive to the stability of the second addition of water, and a stable microemulsion can be formed without adding hot water.

[0111] In order to verify that 20% of the water (the same as the amount of emulsifier) ​​is added once and the remaining water is added at room temperature to produce triacontanol microemulsion, we tested the microemulsion prepared by process 1 of this embodiment according to the indicators of the microemulsion. The test results are shown in Table 21.

[0112] Table 21 Quality test results of 0.1% triacontanol microemulsion

[0113]

[0114]

[0115] It can be seen that the various indicators of the microemulsion prepared by process 1 of this embodiment are qualified. The preparation process of adding water in the same amount as the emulsifier for the first time and adding the remaining water at room temperature can produce a microemulsion that meets the requirements, which can greatly reduce production energy consumption.

[0116] The above-mentioned embodiments only express the specific implementation methods of the present application, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the protection scope of the present application. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the technical solution concept of the present application, and these all belong to the protection scope of the present application.

Claims

1. A triacontanol microemulsion, characterized in that: The triacontanol microemulsion is composed of the following components in percentage by mass: 0.1% of triacontanol original drug, 10-30% of emulsifier, 2-7% of lipophilic regulator, and the balance of water; wherein the emulsifier is mainly a fatty alcohol polyoxyethylene ether with an HLB value of not less than 13; and the lipophilic regulator is an ester environmentally friendly solvent with a dielectric constant of less than 5.

2. The triacontanol microemulsion according to claim 1, characterized in that The emulsifier also uses alkylphenol polyoxyethylene ether TX-15 as an auxiliary emulsifier, and the mass ratio of the main emulsifier to the auxiliary emulsifier is 7-13:

1.

3. The triacontanol microemulsion according to claim 2, characterized in that The mass ratio of the primary emulsifier to the auxiliary emulsifier is 9-11:

1.

4. The triacontanol microemulsion according to claim 1, characterized in that The mass percentage of the emulsifier in the triacontanol microemulsion is 17-25%.

5. The triacontanol microemulsion according to claim 5, characterized in that The mass percentage of the emulsifier in the triacontanol microemulsion is 18-20%.

6. The triacontanol microemulsion according to claim 1, characterized in that The lipophilic regulator is one or more of soybean oil, sesame oil, peanut oil, sunflower seed oil, castor oil, fatty acid methyl ester, methyl oleate, and ethyl oleate.

7. The triacontanol microemulsion according to claim 1, characterized in that The mass percentage of the lipophilic regulator in the triacontanol microemulsion is 3-6%.

8. The method for preparing the triacontanol microemulsion according to any one of claims 1 to 7, characterized in that: The method comprises the following steps: mixing triacontanol, an emulsifier, a lipophilic regulator and water not less than the amount of the emulsifier in the formula, heating to 90°C and stirring, stopping heating and keeping stirring when the mixture is stirred to a clear and transparent state, then adding the remaining water in the formula under stirring, continuing to stir until it is clear and transparent, and obtaining a triacontanol microemulsion when the temperature drops to room temperature.

9. The method for preparing the triacontanol microemulsion according to claim 8, characterized in that: The mass ratio of water to emulsifier added for the first time is 1-1.5:

1.

10. The method for preparing the triacontanol microemulsion according to claim 9, characterized in that: The mass ratio of water to emulsifier added for the first time is 1-1.2:1.

Images