Phosphine Pouring Solution and its Preparation Method

Abstract

This application relates to the field of pharmaceutical formulation technology, specifically to a phoxim pourable solution and its preparation method. The phoxim pourable solution, by weight, comprises: 6-8 parts of crude phoxim, 0.1-0.2 parts of colorant, and 50-100 parts of solvent; wherein the crude phoxim contains not less than 95% cis-phoxim and has a water content not exceeding 0.2%. The preparation method of the phoxim pourable solution includes the following steps: weighing the components, weighing the crude phoxim, colorant, and solvent according to the labeled amounts; dissolving the components, adding the solvent to a mixing tank, then adding the crude phoxim and stirring to dissolve, followed by adding the colorant and stirring continuously until dissolved; filtering the solution through a 0.45μm filter, sampling and testing, and transferring the solution to a container after passing the test. Using the above technical solution, the prepared phoxim pourable solution can be more stable, facilitating the implementation of its pharmacological effects.

Description

Technical Field

[0001] This application relates to the field of pharmaceutical formulation technology, specifically to a phoxim pourable solution and its preparation method. Background Technology

[0002] Parasitic infections in animals, especially livestock (cattle, sheep, pigs, etc.), pose a great threat to the breeding industry and, to some extent, restrict its development.

[0003] Phoxim, as an organophosphorus insecticide, is characterized by high efficiency, low toxicity, broad spectrum, and long residual effect. It has a strong contact killing effect on pests and can treat various external parasitic diseases of livestock, such as cattle warty flies, sheep mange, swine scabies, and blight.

[0004] Pour-over formulations are a new dosage form designed based on the physiological characteristics of animals and the characteristics of drug administration, and have the following advantages:

[0005] (1) The absorption of the drug is not affected by the digestive system such as the gastrointestinal tract, reducing the instability of the deworming effect caused by individual differences; (2) The operation is safe, without the need to capture animals or administer drugs orally or by injection, reducing stress response and avoiding adverse effects on animal growth; (3) The method of use is simple, small animals can be directly applied, and large animals can be poured along their backs, without the need for professional veterinarians to operate, making it easier to promote.

[0006] However, existing phoxim spray solutions do not adhere well to the surface of animals, affecting their efficacy. Therefore, there is an urgent need in the field for a phoxim spray solution and its preparation method to solve the above problems, hence this application is filed. Summary of the Invention

[0007] The purpose of this application is to provide a phorate pourable solution and a method for preparing the same, in order to solve at least one of the technical problems described in the background art.

[0008] Specifically, in a first aspect of this application, a phoxim pourable solution is provided, comprising, by weight, the following components:

[0009] 6-8 parts of crude phoxim.

[0010] Colorant 0.1-0.2 parts,

[0011] Solvent 50-100 parts,

[0012] The crude oil containing phorate contains no less than 95% cis-phorate and has a water content of no more than 0.2%.

[0013] By adopting the above technical solution and controlling the quality indicators of crude phoxim, the prepared phoxim pourable solution can be made more stable, making it easier to implement its efficacy.

[0014] Preferably, the solvent is selected from one or more of ethanol, propanol, butanol, propylene glycol, glycerol, and isopropanol.

[0015] Preferably, the colorant is selected from one or more of crystal violet, oil violet, and oil blue.

[0016] Preferably, the phorate pouring solution comprises, by weight, the following components:

[0017] 7.7 parts of crude phoxim.

[0018] 0.12 parts colorant,

[0019] 80 parts solvent.

[0020] Preferably, the phorate pouring solution further comprises, by weight, the following components:

[0021] 0.2-1.2 parts of isotriacontane.

[0022] Preferably, the phorate pouring solution further comprises, by weight, the following components:

[0023] Polyvinylpyrrolidone, wherein the weight ratio of polyvinylpyrrolidone to isotriacontane is 1:10-2:5.

[0024] Preferably, the polyvinylpyrrolidone is polyvinylpyrrolidone K30.

[0025] By adopting the above technical solution and adding isotriacontane, the adhesion of phoxim spray solution to the animal body surface can be improved, thereby increasing the duration of drug action; furthermore, the addition of polyvinylpyrrolidone can ensure the stability of the product.

[0026] A second aspect of this application provides a method for preparing a phoxim pourable solution as described in the first aspect, comprising the steps of:

[0027] Weigh the components, including crude phoxim, colorant, and solvent, according to the labeled amounts;

[0028] The components are dissolved by adding solvent to the mixing tank, adding crude phoxim and stirring to dissolve, then adding colorant and stirring continuously to dissolve.

[0029] The solution is filtered through a 0.45μm filter, sampled and tested, and if it passes the test, the liquid is transferred to a container.

[0030] Preferably, the component dissolution step is carried out at a temperature of 20-30°C.

[0031] Preferably, the solvent is isopropanol.

[0032] A third aspect of this application provides a method for preparing a phoxim pourable solution as described in the first aspect, comprising the steps of:

[0033] Weigh the components according to the labeled amounts: crude octyl phosphate, colorant, solvent, isotriacontane, and polyvinylpyrrolidone.

[0034] In the first dissolution step, after adding 1 / 3 to 1 / 2 of the labeled amount of solvent to the first mixing tank, add isotriacontane and polyvinylpyrrolidone in sequence, and stir at a temperature of 60-70℃ to ensure that it is fully dissolved.

[0035] In the second dissolution step, after adding 1 / 3 to 1 / 2 of the labeled amount of solvent to the second mixing tank, add crude phoxim and stir to dissolve it completely.

[0036] In the mixing step, the solutions obtained in the first dissolution step and the second dissolution step are mixed, and then the colorant is added and stirred continuously until it dissolves. After it dissolves, the solvent is added to the indicated amount.

[0037] The solution is filtered through a 0.45μm filter, sampled and tested, and if it passes the test, the liquid is transferred to a container.

[0038] Preferably, in the second dissolution step, the temperature is controlled at 20-30°C.

[0039] Preferably, the temperature is controlled at 20-30°C during the mixing step.

[0040] Preferably, the solvent is isopropanol.

[0041] In summary, this application has the following beneficial effects:

[0042] 1. The phoxim pourable solution provided in this application, by controlling the quality indicators of phoxim crude oil, can make the prepared phoxim pourable solution more stable and facilitate the implementation of its efficacy.

[0043] 2. The phoxim pourable solution provided in this application, by adding isotriatriane, can improve the adhesion of the phoxim pourable solution to the animal body surface, thereby increasing the duration of drug action; furthermore, the addition of polyvinylpyrrolidone can ensure the stability of the product.

[0044] 3. The method for preparing phoxim pourable solution provided in this application can prepare phoxim pourable solution with a relatively simple process and ensure that the components are fully dissolved, thereby ensuring the stability of the product. Detailed Implementation

[0045] The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with this application. Rather, they are merely examples of apparatuses and methods consistent with some aspects of this application as detailed in the appended claims.

[0046] The terminology used in this application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. The singular forms “a,” “the,” and “the” used in this application and the appended claims are also intended to include the plural forms unless the context clearly indicates otherwise. It should also be understood that the term “and / or” as used herein refers to and includes any or all possible combinations of one or more of the associated listed items.

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

[0048] In existing technologies, phoxim spray solution is commonly used to treat various ectoparasitic diseases in livestock. Its ease of use eliminates the need to capture animals or administer medication individually via oral gavage or injection, reducing stress and avoiding adverse effects on animal growth, making it widely favored by farmers. However, existing phoxim spray solutions do not adhere well to the animal's skin and easily detach during animal activity or in humid conditions, affecting their efficacy.

[0049] In view of the above, the inventive concept of this application is to provide a phoxim pourable solution and its preparation method that can solve the above-mentioned technical problems. The phoxim pourable solution, by weight, comprises: 5-8 parts of crude phoxim, 0.1-0.2 parts of colorant, and 50-100 parts of solvent. The crude phoxim contains not less than 95% cis-phoxim and has a water content not exceeding 0.2%. By using the technical solution provided in this application and controlling the quality indicators of the crude phoxim, the prepared phoxim pourable solution can be made more stable, facilitating the implementation of its efficacy.

[0050] Before introducing the technical solution of this application, the main components involved in this application will be introduced first. It should be noted that all compounds not specifically emphasized in this application can be purchased commercially, and are not limited to the few described below, nor are they limited to the sources listed below.

[0051] Crude phoxim: Purchased from Shandong Essen Chemical Co., Ltd., containing no less than 95% cis-phoxim.

[0052] Crystal violet, oil violet, and oil blue: purchased from Shanghai Dyestuff Research Institute Co., Ltd.

[0053] Ethanol, propanol, butanol, propylene glycol, glycerol, and isopropanol: purchased from Tianjin Beichen Fangzheng Reagent Factory.

[0054] Isotriane (or squalane): Purchased from Hubei Dongcao Chemical Technology Co., Ltd.

[0055] Polyvinylpyrrolidone: Purchased from Shaanxi Zhengyi Pharmaceutical Excipients Co., Ltd.

[0056] To better understand the above technical solutions, the following detailed descriptions will be provided in conjunction with specific implementation methods. Those skilled in the art should also understand that the reaction times and drug dosages involved in this application cannot be absolutely precise in actual production, but are all within the allowable error range. For example, if the desired sample heating time is 30 minutes, the actual operation may be 30 minutes plus or minus 1 second; if the desired sample weight is 30g, the actual weight may be 30.001g or 29.998g.

[0057] Experiment 1: Viscosity Test

[0058] The viscosity of the sample at 37°C was determined using the viscosity measurement method described in GB / T 10247-2008.

[0059] Experiment Example 2 Accelerated Test

[0060] This experimental example conducts an accelerated test based on a simulated drug application environment. The specific experimental method is as follows:

[0061] The containers holding the phoxim pouring solution were stored at 37±2℃, relative humidity 60±5%RH, and light intensity 1000±100Lx. The properties of the phoxim pouring solution were tested at 0, 1, 3, and 6 months.

[0062] Experiment Example 3: Insect Repellent Test

[0063] Clinical trials were conducted on the prepared phoxim pourable solution, and the test method was as follows:

[0064] The experimental animals were yaks that had been severely infected with warfly larvae over the years, and the cattle were selected from 1.5 to 3 years old; they were randomly divided into groups of 10, and each group was treated with 50 mg / kg of phoxim solution;

[0065] Administration method: Before administration, calculate the dosage for each head using the formula: Body weight (kg) = [Chest circumference (cm)] 2 Calculate the animal's weight using [×body length (cm) ÷ 10800] × 0.85, and then calculate the dosage based on that weight. Apply the designed dosage of drug along the midline of the back to each animal, marking each animal. After administration, allow the animals to graze freely in their original pastures. Observe the feed intake, mental state, and defecation of the experimental group cattle for 7 days after drug administration; the control group cattle were given a placebo (water for injection).

[0066] Efficacy check: After 180 days of administration, examine the skin on the backs of yaks in the experimental and control groups for the presence of galls and worm holes. Based on the increase, decrease, and disappearance of galls and worm holes, calculate the results using the following formula to evaluate the control effect: Deworming rate (%) = (Average number of galls in the control group - Average number of galls in the experimental group) / Average number of galls in the control group × 100%.

[0067] Experiment Example 4

[0068] This experiment measured the viscosity of phoxim pouring solution under different preparation schemes. Five samples were prepared for each scheme, and parallel experiments were conducted to measure the solution viscosity. The average value was then taken.

[0069] Option A

[0070] This scheme prepares phorate pourable solution using the following method:

[0071] Weigh the components as indicated: 6 parts of phoxim crude oil, 0.1 parts of oil-soluble blue, and 50 parts of isopropanol; wherein the phoxim crude oil contains 98% cis-phoxim and has a water content of 0.2%.

[0072] The components are dissolved by adding isopropanol to the mixing tank, then adding crude phoxim and stirring to dissolve it, followed by adding oil blue and stirring continuously until dissolved; this step is carried out at a temperature of 25°C.

[0073] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0074] Option B

[0075] This scheme prepares phorate pourable solution using the following method:

[0076] Weigh the components as indicated: 8 parts of phoxim crude oil, 0.2 parts of oil-soluble blue, and 100 parts of isopropanol; wherein the phoxim crude oil contains 98% cis-phoxim and has a water content of 0.2%.

[0077] The components are dissolved by adding isopropanol to the mixing tank, then adding crude phoxim and stirring to dissolve it, followed by adding oil blue and stirring continuously until dissolved; this step is carried out at a temperature of 25°C.

[0078] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0079] Option C

[0080] This scheme prepares phorate pourable solution using the following method:

[0081] The components were weighed as follows: 6 parts of crude phoxim, 0.1 parts of oil-soluble blue, 50 parts of isopropanol, and 1.2 parts of isotriacontane, according to the labeled amounts; wherein, the crude phoxim contained 98% cis-phoxim and had a water content of 0.2%.

[0082] The components are dissolved by adding isopropanol to the mixing tank, then adding crude octyl phosphate and stirring to dissolve, followed by adding isotriacontane and stirring to dissolve, and finally adding oil blue while stirring continuously to dissolve. This step is carried out at a temperature of 25°C.

[0083] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0084] Option D

[0085] This scheme prepares phorate pourable solution using the following method:

[0086] The components were weighed as follows: 6 parts of phoxim crude oil, 0.1 parts of oil-soluble blue, 50 parts of isopropanol, and 3 parts of isotriacontane, according to the labeled amounts; wherein the phoxim crude oil contains 98% cis-phoxim and has a water content of 0.2%.

[0087] The components are dissolved by adding isopropanol to the mixing tank, then adding crude octyl phosphate and stirring to dissolve, followed by adding isotriacontane and stirring to dissolve, and finally adding oil blue while stirring continuously to dissolve. This step is carried out at a temperature of 25°C.

[0088] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0089] Option E

[0090] This scheme prepares phorate pourable solution using the following method:

[0091] The components were weighed as follows: 8 parts of crude phoxim, 0.2 parts of oil-soluble blue, 100 parts of isopropanol, and 0.2 parts of isotriacontane, according to the labeled amounts; wherein the crude phoxim contained 98% cis-phoxim and had a water content of 0.2%.

[0092] The components are dissolved by adding isopropanol to the mixing tank, then adding crude octyl phosphate and stirring to dissolve, followed by adding isotriacontane and stirring to dissolve, and finally adding oil blue while stirring continuously to dissolve. This step is carried out at a temperature of 25°C.

[0093] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0094] Option F

[0095] This scheme prepares phorate pourable solution using the following method:

[0096] The components were weighed as follows: 8 parts of crude phoxim, 0.2 parts of oil-soluble blue, 100 parts of isopropanol, and 0.1 parts of isotriacontane, according to the labeled amounts; wherein, the crude phoxim contained 98% cis-phoxim and had a water content of 0.2%;

[0097] The components are dissolved by adding isopropanol to the mixing tank, then adding crude octyl phosphate and stirring to dissolve, followed by adding isotriacontane and stirring to dissolve, and finally adding oil blue while stirring continuously to dissolve. This step is carried out at a temperature of 25°C.

[0098] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0099] The viscosity of the phoxim pourable solution of schemes A-F was determined according to the method in Experimental Example 1. The test results are shown in Table 1.

[0100] Table 1 Viscosity of Phosphine Pouring Solution for Schemes A-F

[0101] Group Viscosity (mPa·s) Option A 2.8±0.1 Option B 3.2±0.2 Option C 7.9±0.4 Option D 8.3±0.5 Option E 5.1±0.2 Option F 3.9±0.2

[0102] Based on the viscosity data of the phoxim pourable solution in Table 1, we can preliminarily conclude that:

[0103] First, adding an appropriate amount of isotriacontane can significantly increase the viscosity of the solution, thereby increasing the adhesion of the product to the animal's body surface and helping to exert the drug's efficacy.

[0104] Second, an excessively high content of isotriacontane does not significantly increase the solution viscosity (compared to scheme C in scheme D), and it is prone to changing the properties of the solution, so this scheme is not suitable. An excessively low content of isotriacontane (scheme F) has little effect on the solution viscosity, so this scheme is also not suitable.

[0105] Furthermore, insect repellent tests were conducted on schemes A to F according to the method in Experimental Example 3. The test results are shown in Table 2.

[0106] Table 2 Results of insect repellent trials for schemes A-F

[0107]

[0108]

[0109] Based on the deworming test data in Table 2, we can preliminarily conclude that:

[0110] First, the AF scheme provided in this application has a significantly higher deworming rate than the control group, indicating that the above scheme has a relatively significant deworming effect.

[0111] Second, compared with scheme A, scheme C showed a significant increase in insect repellency, and compared with scheme B, scheme E showed a significant increase in insect repellency. This indicates that the increased viscosity of the phoxim solution has a positive impact on the insect repellency effect of the drug, and also shows that the preparation schemes of schemes C and E can achieve good insect repellency effects.

[0112] Experiment Example 5 Stability Test

[0113] This experiment determined the stability of phoxim pourable solution under different preparation schemes. Five samples were prepared for each scheme, and parallel experiments were conducted to detect the solution viscosity and take the average value.

[0114] Option G

[0115] This scheme prepares phorate pourable solution using the following method:

[0116] The components were weighed as follows: 6 parts of crude phoxim, 0.1 parts of oil-soluble blue, 50 parts of isopropanol, 1.2 parts of isotriacontane, and 0.12 parts of polyvinylpyrrolidone K30 were weighed according to the labeled amounts; wherein, the crude phoxim contained 98% cis-phoxim and had a water content of 0.2%.

[0117] In the first dissolution step, after adding 1 / 3 of the labeled amount of isopropanol to the first mixing tank, add isotriacontane and polyvinylpyrrolidone K30, and stir at a temperature of 65°C to fully dissolve them.

[0118] The second dissolution step involves adding 1 / 3 of the labeled amount of isopropanol to the second mixing tank, followed by the addition of crude octyl phosphate, and stirring until fully dissolved. This step is carried out at a temperature of 25°C.

[0119] In the mixing step, the solutions obtained from the first dissolution step and the second dissolution step are mixed, and then oil blue is added and stirred continuously until dissolved. After dissolution, isopropanol is added to bring the volume to the labeled amount. This step is carried out at a temperature of 25°C.

[0120] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0121] Option H

[0122] This scheme prepares phorate pourable solution using the following method:

[0123] The components were weighed as follows: 8 parts of crude phoxim, 0.2 parts of oil-soluble blue, 100 parts of isopropanol, 0.2 parts of isotriacontane, and 0.08 parts of polyvinylpyrrolidone K30 were weighed according to the labeled amounts; wherein, the crude phoxim contained 98% cis-phoxim and had a water content of 0.2%.

[0124] In the first dissolution step, after adding 1 / 3 of the labeled amount of isopropanol to the first mixing tank, add isotriacontane and polyvinylpyrrolidone K30, and stir at a temperature of 65°C to fully dissolve them.

[0125] The second dissolution step involves adding 1 / 3 of the labeled amount of isopropanol to the second mixing tank, followed by the addition of crude octyl phosphate, and stirring until fully dissolved. This step is carried out at a temperature of 25°C.

[0126] In the mixing step, the solutions obtained from the first dissolution step and the second dissolution step are mixed, and then oil blue is added and stirred continuously until dissolved. After dissolution, isopropanol is added to bring the volume to the labeled amount. This step is carried out at a temperature of 25°C.

[0127] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0128] The phoxim content (ratio of current content to labeled amount) of schemes A-H was determined according to the method in Experimental Example 2, and the solution state was observed. The experimental results are shown in Table 3.

[0129] Table 3 Accelerated test results of schemes A-H

[0130]

[0131] Based on the accelerated test data in Table 3, we can preliminarily conclude that:

[0132] First, comparing scheme A with schemes C and D, although the viscosity of the solution obtained by schemes C and D is higher than that of scheme A, its stability in accelerated testing is significantly lower than that of scheme A. Similarly, the viscosity of the solution obtained by schemes E and F is higher than that of scheme B, but its stability in accelerated testing is significantly lower than that of scheme B. It is speculated that although the addition of isotriacontane can increase the viscosity of the solution to a certain extent, it will have an adverse effect on the stability of the solution.

[0133] Second, comparing scheme G with schemes C and D, scheme G showed a significantly higher phoxim content than schemes C and D after 6 months of accelerated testing. It is speculated that adding an appropriate amount of polyvinylpyrrolidone K30 to scheme G can improve the stability of the solution to a certain extent. Similarly, scheme H also showed a similar pattern with schemes E and F.

[0134] Example 1

[0135] This embodiment prepares a phoxim pourable solution using the following method:

[0136] Weigh the components as indicated: 6 parts of phoxim crude oil, 0.1 parts of oil-soluble blue, and 50 parts of isopropanol; wherein the phoxim crude oil contains 98% cis-phoxim and has a water content of 0.2%.

[0137] The components are dissolved by adding isopropanol to the mixing tank, then adding crude phoxim and stirring to dissolve it, followed by adding oil-soluble blue and stirring continuously until dissolved; this step is carried out at a temperature of 20°C.

[0138] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0139] Example 2

[0140] This embodiment prepares a phoxim pourable solution using the following method:

[0141] The components were weighed as follows: 7.7 parts of phoxim crude oil, 0.12 parts of oil-soluble blue, and 80 parts of isopropanol were weighed according to the labeled amounts; wherein, the phoxim crude oil contained 98% cis-phoxim and had a water content of 0.2%;

[0142] The components are dissolved by adding isopropanol to the mixing tank, then adding crude phoxim and stirring to dissolve it, followed by adding oil blue and stirring continuously until dissolved; this step is carried out at a temperature of 25°C.

[0143] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0144] Example 3

[0145] This embodiment prepares a phoxim pourable solution using the following method:

[0146] Weigh the components as indicated: 8 parts of phoxim crude oil, 0.2 parts of oil-soluble blue, and 100 parts of isopropanol; wherein the phoxim crude oil contains 98% cis-phoxim and has a water content of 0.2%.

[0147] The components are dissolved by adding isopropanol to the mixing tank, then adding crude phoxim and stirring to dissolve it, followed by adding oil-soluble blue and stirring continuously until dissolved; this step is carried out at a temperature of 30°C.

[0148] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0149] Example 4

[0150] This embodiment prepares a phoxim pourable solution using the following method:

[0151] The components were weighed as follows: 6 parts of crude phoxim, 0.1 parts of oil-soluble blue, 50 parts of isopropanol, and 1.2 parts of isotriacontane, according to the labeled amounts; wherein, the crude phoxim contained 98% cis-phoxim and had a water content of 0.2%.

[0152] The components were dissolved by adding isopropanol to the mixing tank, followed by crude octyl phosphate and stirring to dissolve. Then, isotriacontane was added and stirred to dissolve. Finally, oil blue was added, and stirring was continued throughout the process until the components were dissolved. This step was carried out at a temperature of 20°C.

[0153] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0154] Example 5

[0155] This embodiment prepares a phoxim pourable solution using the following method:

[0156] The components were weighed as follows: 7.7 parts of phoxim crude oil, 0.12 parts of oil-soluble blue, 80 parts of isopropanol, and 0.6 parts of isotriacontane, according to the labeled amounts; wherein, the phoxim crude oil contains 98% cis-phoxim and has a water content of 0.2%;

[0157] The components are dissolved by adding isopropanol to the mixing tank, then adding crude octyl phosphate and stirring to dissolve, followed by adding isotriacontane and stirring to dissolve, and finally adding oil blue while stirring continuously to dissolve. This step is carried out at a temperature of 25°C.

[0158] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0159] Example 6

[0160] This embodiment prepares a phoxim pourable solution using the following method:

[0161] The components were weighed as follows: 8 parts of crude phoxim, 0.2 parts of oil-soluble blue, 100 parts of isopropanol, and 0.2 parts of isotriacontane, according to the labeled amounts; wherein the crude phoxim contained 98% cis-phoxim and had a water content of 0.2%.

[0162] The components are dissolved by adding isopropanol to the mixing tank, then adding crude octyl phosphate and stirring to dissolve, followed by adding isotriacontane and stirring to dissolve, and finally adding oil blue while stirring continuously to dissolve. This step is carried out at a temperature of 30°C.

[0163] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0164] Example 7

[0165] This embodiment prepares a phoxim pourable solution using the following method:

[0166] The components were weighed as follows: 6 parts of crude phoxim, 0.1 parts of oil-soluble blue, 50 parts of isopropanol, 1.2 parts of isotriacontane, and 0.12 parts of polyvinylpyrrolidone K30 were weighed according to the labeled amounts; wherein, the crude phoxim contained 98% cis-phoxim and had a water content of 0.2%.

[0167] In the first dissolution step, after adding 1 / 3 of the labeled amount of isopropanol to the first mixing tank, add isotriacontane and polyvinylpyrrolidone K30, and stir at a temperature of 60°C to fully dissolve them.

[0168] The second dissolution step involves adding 1 / 3 of the labeled amount of isopropanol to the second mixing tank, followed by the addition of crude octyl phosphate, and stirring until fully dissolved. This step is carried out at a temperature of 20°C.

[0169] In the mixing step, the solutions obtained from the first dissolution step and the second dissolution step are mixed, and then oil blue is added and stirred continuously until dissolved. After dissolution, isopropanol is added to bring the volume to the labeled amount. This step is carried out at a temperature of 20°C.

[0170] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0171] Example 8

[0172] This embodiment prepares a phoxim pourable solution using the following method:

[0173] The components were weighed as follows: 7.7 parts of crude phoxim, 0.12 parts of oil-soluble blue, 80 parts of isopropanol, 0.6 parts of isotriacontane, and 0.12 parts of polyvinylpyrrolidone K30 were weighed according to the labeled amounts; wherein, the crude phoxim contained 98% cis-phoxim and had a water content of 0.2%.

[0174] In the first dissolution step, after adding 1 / 3 of the labeled amount of isopropanol to the first mixing tank, add isotriacontane and polyvinylpyrrolidone K30, and stir at a temperature of 65°C to fully dissolve them.

[0175] The second dissolution step involves adding 1 / 3 of the labeled amount of isopropanol to the second mixing tank, followed by the addition of crude octyl phosphate, and stirring until fully dissolved. This step is carried out at a temperature of 25°C.

[0176] In the mixing step, the solutions obtained from the first dissolution step and the second dissolution step are mixed, and then oil blue is added and stirred continuously until dissolved. After dissolution, isopropanol is added to bring the volume to the labeled amount. This step is carried out at a temperature of 25°C.

[0177] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0178] Example 9

[0179] This embodiment prepares a phoxim pourable solution using the following method:

[0180] The components were weighed as follows: 8 parts of crude phoxim, 0.2 parts of oil-soluble blue, 100 parts of isopropanol, 0.2 parts of isotriacontane, and 0.08 parts of polyvinylpyrrolidone K30 were weighed according to the labeled amounts; wherein, the crude phoxim contained 98% cis-phoxim and had a water content of 0.2%.

[0181] In the first dissolution step, after adding 1 / 3 of the labeled amount of isopropanol to the first mixing tank, add isotriacontane and polyvinylpyrrolidone K30, and stir at a temperature of 70°C to ensure complete dissolution.

[0182] The second dissolution step involves adding 1 / 3 of the labeled amount of isopropanol to the second mixing tank, followed by the addition of crude phoxim, and stirring until fully dissolved. This step is carried out at a temperature of 30°C.

[0183] In the mixing step, the solutions obtained from the first dissolution step and the second dissolution step are mixed, and then oil blue is added and stirred continuously until dissolved. After dissolution, isopropanol is added to bring the volume to the labeled amount. This step is carried out at a temperature of 30°C.

[0184] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0185] Comparative Example 1

[0186] The phorate pourable solution was prepared using the technical solution of Example 4 in existing technology CN114712408A:

[0187] The phorate pouring solution is composed of the following mass percentages:

[0188] The mixture comprises 30% crude phoxim, 1.2% pine oil, 1.5% azone, 15% Tween-80, and ethanol to a total of 100%. The crude phoxim contains 98% cis-phoxim and has a water content of 0.2%.

[0189] Phoxim and pine oil were dissolved in ethanol, and azone and Tween-80 were added. After stirring evenly, a phoxim pourable solution was obtained.

[0190] Comparative Example 2

[0191] The technical solution is basically the same as that in Embodiment 2, with the only difference being:

[0192] The crude phoxim contained 98% cis-phoxim and had a water content of 0.5%.

[0193] Comparative Example 3

[0194] The technical solution is basically the same as that in Embodiment 5, with the only difference being:

[0195] The crude phoxim contained 98% cis-phoxim and had a water content of 0.5%.

[0196] Comparative Example 4

[0197] The technical solution is basically the same as that in Embodiment 8, with the only difference being:

[0198] The crude phoxim contained 98% cis-phoxim and had a water content of 0.5%.

[0199] Comparative Example 5

[0200] The technical solution is basically the same as that in Example 8, the only difference being the preparation method:

[0201] The components were weighed as follows: 7.7 parts of crude phoxim, 0.12 parts of oil-soluble blue, 80 parts of isopropanol, 0.6 parts of isotriacontane, and 0.12 parts of polyvinylpyrrolidone K30 were weighed according to the labeled amounts; wherein, the crude phoxim contained 98% cis-phoxim and had a water content of 0.2%.

[0202] The components are dissolved by adding isopropanol to the mixing tank, then adding crude octyl phosphate and stirring to dissolve, followed by adding isotriacontane and stirring to dissolve, then adding polyvinylpyrrolidone K30 and stirring to dissolve, and finally adding oil blue while stirring continuously to dissolve. This step is carried out at a temperature of 25°C.

[0203] The solution was filtered through a 0.45μm filter to obtain a phoxim pourable solution.

[0204] Comparative Example 6

[0205] The technical solution is basically the same as that in Embodiment 5, with the only difference being:

[0206] Replace isotriacontane with 0.6 parts of polyvinylpyrrolidone K30.

[0207] Furthermore, in the component dissolution step: after adding isopropanol to the mixing tank, crude octyl phosphate is added and stirred to dissolve, followed by the addition of polyvinylpyrrolidone K30 and stirring to dissolve, and finally the addition of oil-soluble blue, with continuous stirring to dissolve; this step is carried out at a temperature of 25°C.

[0208] Example 10

[0209] The stability (month 0 and month 6) of the phoxim spray solution obtained under each scheme of Examples 1-9 and Comparative Examples 1-6, as well as the insect repellency test data, were tested according to the methods of Experimental Examples 2-3. The experimental results are shown in Table 4. After the accelerated test, no visibly turbidity was observed in any of the groups of solutions.

[0210] Table 4 shows the stability and insecticidal data of phoxim drenching solutions obtained in Examples 1-9 and Comparative Examples 1-6.

[0211]

[0212] First, based on the experimental data in Table 4, we can preliminarily conclude that:

[0213] First, the phoxim spraying solutions provided in Examples 4-9 all showed significantly better insect repellent effects than the prior art comparative example 1, indicating that the technical solutions of this application have good application prospects.

[0214] Second, comparing Example 2 with Comparative Example 2, Example 5 with Comparative Example 3, and Example 8 with Comparative Example 4, the phoxim pouring solution prepared in this application has better stability in accelerated experiments when the water content of the phoxim crude oil is low.

[0215] Third, comparing Example 8 and Comparative Example 5, the phoxim pouring solution obtained by using the technique proposed in this application of dissolving isotriacontane and polyvinylpyrrolidone K30 separately and then mixing them exhibits better stability in accelerated experiments.

[0216] Fourth, comparing Example 5 and Comparative Example 6, replacing isotriacontane in the components with polyvinylpyrrolidone K30, although the stability data were relatively normal, the insect repellency data was significantly reduced, indicating that polyvinylpyrrolidone K30 cannot achieve the effect of increasing the adhesion of the solution on the animal's body surface as isotriacontane.

[0217] Fifth, comparing Examples 4-6 with Examples 1-3, the addition of isotriatriane significantly increased the insect repellency rate, but reduced the stability in accelerated tests. Furthermore, comparing Examples 7-9 with Examples 4-6, the addition of polyvinylpyrrolidone K30 to isotriatriane maintained the original stability of the phoxim drenching solution while maintaining a high insect repellency rate.

[0218] In summary, the phoxim pourable solution and its preparation method provided in this application can improve the adhesion of the phoxim pourable solution to the animal body surface by adjusting the product components, thereby increasing the duration and efficacy of the drug, and have good commercial prospects.

[0219] For those skilled in the art, the technical features in the above embodiments can be freely combined, and the resulting technical solutions also belong to the embodiments disclosed in this application.

[0220] Furthermore, without departing from the principles of this application, several improvements and modifications may be made to this application, and these improvements and modifications also fall within the protection scope of the claims of this application.

Claims

1. A phoxim pourable solution, characterized in that: By weight, including components: 6-8 parts of crude phoxim. Colorant 0.1-0.2 parts, Solvent 50-100 parts, 0.2-1.2 parts of isotriacontane, The crude phoxim contains no less than 95% cis-phoxim and no more than 0.2% water; the solvent is selected from one or more of ethanol, propanol, butanol, propylene glycol, glycerol, and isopropanol.

2. The phoxim pourable solution according to claim 1, characterized in that: The colorant is selected from one or more of crystal violet, oil violet, and oil blue.

3. The phoxim pourable solution according to claim 1, characterized in that: The phorate pourable solution, by weight, comprises the following components: 7.7 parts of crude phoxim. 0.12 parts colorant, 80 parts solvent.

4. The phoxim pourable solution according to claim 1, characterized in that: The phorate pourable solution, by weight, also includes the following components: Polyvinylpyrrolidone, wherein the weight ratio of polyvinylpyrrolidone to isotriacontane is 1:10-2:

5.

5. A method for preparing the phorate pourable solution according to any one of claims 1-4, characterized in that: Including the following steps: Weigh the components according to the labeled amounts: crude octyl phosphate, colorant, solvent, isotriacontane, and polyvinylpyrrolidone. In the first dissolution step, after adding 1 / 3 to 1 / 2 of the labeled amount of solvent to the first mixing tank, add isotriacontane and polyvinylpyrrolidone in sequence, and stir at a temperature of 60-70℃ to ensure that it is fully dissolved. In the second dissolution step, after adding 1 / 3 to 1 / 2 of the labeled amount of solvent to the second mixing tank, add crude phoxim and stir to dissolve it completely. In the mixing step, the solutions obtained in the first dissolution step and the second dissolution step are mixed, and then the colorant is added and stirred continuously until it dissolves. After it dissolves, the solvent is added to the indicated amount. The solution is filtered through a 0.45μm filter, sampled and tested, and if it passes the test, the liquid is transferred to a container.

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