Soluble compound sulfachloropyridazine sodium powder and preparation method thereof

Abstract

The invention discloses soluble compound sulfachlorpyridazine sodium powder and a preparation method thereof. The soluble compound sulfachlorpyridazine sodium powder comprises sulfachlorpyridazine sodium, a trimethoprim inclusion compound and a filling agent. Aiming at the problem of acetic acid residue in a process for preparing soluble compound sulfachloropyridazine sodium in the prior art, trimethoprim is included by adopting a cyclodextrin derivative, and a product obtained by spray drying is subjected to acetic acid removal treatment by utilizing a high-temperature blast drying oven, so that the negative influence caused by dissolving trimethoprim by utilizing acetic acid is effectively solved, and the yield of soluble compound sulfachloropyridazine sodium is improved. And cost reduction and benefit increase are realized.

Description

Technical Field

[0001] The invention belongs to the technical field of medicine, and particularly relates to soluble compound sulfachloropyridazine sodium powder and a preparation method thereof. Background Art

[0002] Compound sulfachloropyridazine sodium is a mixed preparation of sulfachloropyridazine sodium and trimethoprim. It is the sulfonamide with the strongest antibacterial activity both in vitro and in vivo, exhibiting broad-spectrum antibacterial properties and excellent inhibitory effects against most Gram-positive and Gram-negative bacteria. It is primarily used to treat Escherichia coli and Pasteurella infections in pigs and chickens, and also has significant effects against coccidia, Toxoplasma gondii, and leukocytozoa. Long-term clinical exploration and validation of combined drug use has shown that a 5:1 ratio of the two drugs is most effective. This combination can simultaneously block folic acid metabolism at two different points, exerting a dual blocking effect, reducing the likelihood of drug-resistant strains and minimizing or delaying the development of bacterial resistance. Furthermore, it achieves a bactericidal effect unattainable by sulfonamides alone, making the combination of trimethoprim and sulfachloropyridazine sodium an ideal veterinary anti-infective drug.

[0003] Currently, research on this compound preparation focuses primarily on dosage forms such as premixes, oral solutions, suspensions, and soluble powders. Premixes are administered through mixed feed, but given the increasing centralization and scale of the livestock industry, this dosage form is no longer widely used. In contrast, powders offer cost advantages in packaging and transportation, as well as greater convenience and stability. In actual use, centralized administration through drinking water allows the active ingredients to be absorbed quickly, achieving optimal blood concentrations and maximizing efficacy. However, sulfachloropyridazine sodium is readily soluble in water, while trimethoprim is essentially insoluble in water, resulting in extremely low bioavailability. This disparity in their solubility makes it difficult to achieve an optimal ratio, significantly impacting the synergistic effect of trimethoprim. In preparation, glacial acetic acid is commonly used to dissolve trimethoprim to prepare compound sulfachloropyridazine sodium, which to some extent addresses trimethoprim's water solubility. However, glacial acetic acid residues are extremely difficult to eliminate. Not only will the solubility of sulfachlorpyrifos sodium in water be reduced, but the product will also have a strong acetic acid smell, which will affect the drinking and feeding of animals. Summary of the Invention

[0004] One of the purposes of the present invention is to provide a soluble compound sulfachloropyridazine sodium powder, which comprises sulfachloropyridazine sodium, a trimethoprim inclusion compound and a filler, wherein the mass ratio of the sulfachloropyridazine sodium, the trimethoprim inclusion compound and the filler is 62.5:12.5:25.

[0005] Furthermore, the trimethoprim inclusion compound is prepared from trimethoprim, a cyclodextrin derivative, a stabilizer and a surfactant, and the mass ratio of trimethoprim, cyclodextrin derivative, stabilizer and surfactant is 12.5-25:25-100:3-5:1-3.

[0006] Furthermore, the cyclodextrin derivative is one or a combination of β-cyclodextrin, methyl-β-cyclodextrin, carboxymethyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, and hydroxypropyl-γ-cyclodextrin; the stabilizer is povidone K30 or povidone K90; and the surfactant is one or a combination of Tween 60, Tween 80, and poloxamer 188.

[0007] Furthermore, the preparation method of the trimethoprim inclusion complex is as follows: trimethoprim, a cyclodextrin derivative, a stabilizer, and a surfactant are added to an acetic acid solution for inclusion, and the inclusion complex solution is dried to obtain the trimethoprim inclusion complex.

[0008] The preparation process of inclusion is as follows: inclusion temperature 60°C-80°C, stirring speed 900-1500r / min, and reaction time 4-8h.

[0009] In one embodiment of the present invention, the inclusion complex solution is first spray-dried to obtain an inclusion complex solid, which is then further dried in a drying oven to obtain the trimethoprim inclusion complex. The spray drying process comprises an inlet air temperature of 190-210°C, an outlet air temperature of 90-110°C, and an atomizing disk speed of 3000-3500 rpm. The drying oven drying conditions are 120-135°C for 4-6 hours.

[0010] Furthermore, the filler is one or a combination of sucralose, maltodextrin, and sucrose.

[0011] The second object of the present invention is to provide a method for preparing the soluble compound sulfachloropyridazine sodium powder, which comprises mixing trimethoprim inclusion compound, sulfachloropyridazine sodium and a filler.

[0012] According to the relevant requirements of the Chinese Veterinary Pharmacopoeia, the content of sulfachloropyridazine sodium in compound sulfachloropyridazine sodium powder is 62.5%, and the content of trimethoprim is 12.5%. Sucrose is contained in the auxiliary material. Therefore, based on this, the present invention has developed a soluble compound sulfachloropyridazine sodium powder. The present invention adopts a simple and easy inclusion compound inclusion technology, and prepares a powder with auxiliary materials such as stabilizers and surfactants, so that the solubility of the trimethoprim component in compound sulfachloropyridazine sodium in water reaches 2500-3000ppm, and it can not precipitate in 12h. In addition, sulfachloropyridazine sodium and trimethoprim meet the ratio requirements, give full play to the synergistic effect of the medicine, reduce production costs, and expand clinical application.

[0013] To address the problem of acetic acid residue in the prior art process for preparing soluble compound sulfachloropyridazine sodium, the present invention uses a cyclodextrin derivative to encapsulate trimethoprim and uses a high-temperature forced air drying oven to remove acetic acid from the spray-dried product, effectively solving the negative impact of using acetic acid to dissolve trimethoprim and achieving cost reduction and efficiency improvement. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 This is the standard curve of trimethoprim.

[0015] Figure 2 This is the solution condition of the sample prepared in Example 2 after being left for 12 hours. DETAILED DESCRIPTION

[0016] The preferred embodiments of the present invention will be described in detail below with reference to the examples. It should be understood that the following examples are provided for illustrative purposes only and are not intended to limit the scope of the present invention. Those skilled in the art may make various modifications and substitutions to the present invention without departing from the purpose and spirit of the present invention.

[0017] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0018] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0019] Example 1

[0020] A method for preparing soluble compound sulfachloropyridazine sodium powder comprises the following steps:

[0021] (1) Weigh the following raw materials: 12.5 g trimethoprim, 50 g β-cyclodextrin, 4.5 g povidone K30, and 2 g Tween 80;

[0022] (2) Dissolve trimethoprim in 50 mL of 0.5% acetic acid solution. After complete dissolution, add the amounts of β-cyclodextrin, povidone K30, and Tween 80 described in step (1) in sequence. The inclusion temperature is 65°C, the reaction speed is 1000 r / min, and the inclusion time is 8 h.

[0023] (3) spray drying the prepared inclusion compound solution to obtain a white inclusion compound powder, wherein the inlet air temperature of the spray drying is 195°C, the outlet air temperature is 90°C, and the atomizing disk speed is 3200 r / min;

[0024] (4) The product was placed in a high-temperature forced air drying oven to remove acetic acid at high temperature. The drying oven temperature was 135°C and the drying time was 4 hours, until there was no acetic acid smell.

[0025] (5) Grind the dried product through an 80-mesh sieve;

[0026] (6) The sieved product was mixed with 62.5 g of sulfachloropyridazine sodium and 25 g of maltodextrin to obtain soluble compound sulfachloropyridazine sodium powder.

[0027] The soluble compound sulfachloropyridazine sodium powder prepared in this example is a dry, loose, uniformly mixed, light yellow powder of uniform color, which passes through an 80-mesh sieve. The solubility of trimethoprim in the powder can reach 2500 ppm.

[0028] Example 2

[0029] A method for preparing soluble compound sulfachloropyridazine sodium powder comprises the following steps:

[0030] (1) Weigh the following raw materials: 12.5 g trimethoprim, 37.5 g hydroxypropyl-β-cyclodextrin, 3 g povidone K90, and 2 g poloxamer 188;

[0031] (2) Dissolve trimethoprim in 50 mL of 0.5% acetic acid solution. After complete dissolution, add the amounts of hydroxypropyl-β-cyclodextrin, povidone K90, and poloxamer 188 described in step (1) in sequence. The inclusion temperature is 60° C., the reaction speed is 1200 rpm, and the inclusion time is 6 h.

[0032] (3) spray drying the prepared inclusion compound solution to obtain a white inclusion compound powder, wherein the inlet air temperature of the spray drying is 200°C, the outlet air temperature is 95°C, and the atomizing disk speed is 3200 r / min;

[0033] (4) The product was placed in a high-temperature forced air drying oven to remove acetic acid at high temperature. The drying oven temperature was 135°C and the drying time was 4 hours.

[0034] (5) Grind the dried product through an 80-mesh sieve;

[0035] (6) The sieved product was mixed with 62.5 g of sulfachloropyridazine sodium and 25 g of maltodextrin to obtain soluble compound sulfachloropyridazine sodium powder.

[0036] The soluble compound sulfachloropyridazine sodium powder prepared in this example is a dry, loose, uniformly mixed, light yellow powder of uniform color, which passes through an 80-mesh sieve. The solubility of trimethoprim can reach 3000 ppm.

[0037] Example 3

[0038] A method for preparing soluble compound sulfachloropyridazine sodium powder comprises the following steps:

[0039] (1) Weigh the following raw materials: 12.5 g trimethoprim, 56 g methyl-β-cyclodextrin, 3 g povidone K90, and 2 g poloxamer 188;

[0040] (2) Dissolve trimethoprim in 50 mL of 0.5% acetic acid solution. After complete dissolution, add the amounts of methyl-β-cyclodextrin, povidone K90, and poloxamer 188 described in step (1) in sequence. The inclusion temperature is 65°C, the reaction speed is 1000 r / min, and the inclusion time is 8 h.

[0041] (3) spray drying the prepared inclusion compound solution to obtain a white inclusion compound powder, wherein the inlet air temperature of the spray drying is 190°C, the outlet air temperature is 90°C, and the atomizing disk speed is 3200 r / min;

[0042] (4) The product was placed in a high-temperature forced air drying oven to remove acetic acid at high temperature. The drying oven temperature was 130°C and the drying time was 4 hours.

[0043] (5) Grind the dried product through an 80-mesh sieve;

[0044] (6) The sieved product was mixed with 62.5 g of sulfachloropyridazine sodium and 25 g of maltodextrin to obtain soluble compound sulfachloropyridazine sodium powder.

[0045] The soluble compound sulfachloropyridazine sodium powder prepared in this example is a dry, loose, uniformly mixed, light yellow powder of uniform color, which passes through an 80-mesh sieve. The solubility of trimethoprim in the powder can reach 2800 ppm.

[0046] Example 4

[0047] A method for preparing soluble compound sulfachloropyridazine sodium powder comprises the following steps:

[0048] (1) Weigh the following raw materials: 12.5 g trimethoprim, 37.5 g hydroxypropyl-β-cyclodextrin, 3 g povidone K30, and 2 g Tween 80;

[0049] (2) Dissolve trimethoprim in 50 mL of 0.5% acetic acid solution. After complete dissolution, add the amounts of hydroxypropyl-β-cyclodextrin, povidone K30, and Tween 80 described in step (1) in sequence. The inclusion temperature is 60° C., the reaction speed is 1200 rpm, and the inclusion time is 6.5 h.

[0050] (3) spray drying the prepared inclusion compound solution to obtain a white inclusion compound powder, wherein the inlet air temperature of the spray drying is 195°C, the outlet air temperature is 90°C, and the atomizing disk speed is 3200 r / min;

[0051] (4) The product was placed in a high-temperature forced air drying oven to remove acetic acid at high temperature. The drying oven temperature was 135°C and the drying time was 4 hours.

[0052] (5) Grind the dried product through an 80-mesh sieve;

[0053] (6) The sieved product was mixed with 62.5 g of sulfachloropyridazine sodium and 25 g of maltodextrin to obtain soluble compound sulfachloropyridazine sodium powder.

[0054] The soluble compound sulfachloropyridazine sodium powder prepared in this example is a dry, loose, uniformly mixed, light yellow powder of uniform color, which passes through an 80-mesh sieve. The solubility of trimethoprim can reach 3000 ppm.

[0055] Example 5

[0056] A method for preparing soluble compound sulfachloropyridazine sodium powder comprises the following steps:

[0057] (1) Weigh the following raw materials: 12.5 g trimethoprim, 55 g carboxymethyl-β-cyclodextrin, 3 g povidone K30, and 2 g poloxamer 188;

[0058] (2) Dissolve trimethoprim in 50 mL of 0.5% acetic acid solution. After complete dissolution, add the amounts of carboxymethyl-β-cyclodextrin, povidone K30, and poloxamer 188 described in step (1) in sequence. The inclusion temperature is 60° C., the reaction speed is 1000 rpm, and the inclusion time is 8 h.

[0059] (3) spray drying the prepared inclusion compound solution to obtain a white inclusion compound powder, wherein the inlet air temperature of the spray drying is 190°C, the outlet air temperature is 90°C, and the atomizing disk speed is 3200 r / min;

[0060] (4) The product was placed in a high-temperature forced air drying oven to remove acetic acid at high temperature. The drying oven temperature was 130°C and the drying time was 4 hours.

[0061] (5) Grind the dried product through an 80-mesh sieve;

[0062] (6) The sieved product was mixed with 62.5 g of sulfachloropyridazine sodium and 25 g of maltodextrin to obtain soluble compound sulfachloropyridazine sodium powder.

[0063] The soluble compound sulfachloropyridazine sodium powder prepared in this example is a dry, loose, uniformly mixed, light yellow powder of uniform color, which passes through an 80-mesh sieve. The solubility of trimethoprim in the powder can reach 2600 ppm.

[0064] Example 6

[0065] A method for preparing soluble compound sulfachloropyridazine sodium powder comprises the following steps:

[0066] (1) Weigh the following raw materials: 12.5 g trimethoprim, 55 g carboxymethyl-β-cyclodextrin, 3 g povidone K30, and 2 g Tween 80;

[0067] (2) Dissolve trimethoprim in 50 mL of 0.5% acetic acid solution. After complete dissolution, add the amounts of carboxymethyl-β-cyclodextrin, povidone K30, and Tween 80 described in step (1) in sequence. The inclusion temperature is 60° C., the reaction speed is 1000 r / min, and the inclusion time is 8 h.

[0068] (3) spray drying the prepared inclusion compound solution to obtain a white inclusion compound powder, wherein the inlet air temperature of the spray drying is 195°C, the outlet air temperature is 90°C, and the atomizing disk speed is 3200 r / min;

[0069] (4) The product was placed in a high-temperature forced air drying oven to remove acetic acid at high temperature. The drying oven temperature was 135°C and the drying time was 4 hours.

[0070] (5) Grind the dried product through an 80-mesh sieve;

[0071] (6) The sieved product was mixed with 62.5 g of sulfachloropyridazine sodium and 25 g of maltodextrin to obtain soluble compound sulfachloropyridazine sodium powder.

[0072] The soluble compound sulfachloropyridazine sodium powder prepared in this example is a dry, loose, uniformly mixed, light yellow powder of uniform color, which passes through an 80-mesh sieve. The solubility of trimethoprim in the powder can reach 2500 ppm.

[0073] Example 7

[0074] A method for preparing soluble compound sulfachloropyridazine sodium powder comprises the following steps:

[0075] (1) Weigh the following raw materials: 12.5 g trimethoprim, 40 g sulfobutyl-β-cyclodextrin, 3 g povidone K30, and 2 g poloxamer 188;

[0076] (2) Dissolve trimethoprim in 50 mL of 0.5% acetic acid solution. After complete dissolution, add sulfobutyl-β-cyclodextrin, povidone K30, and poloxamer 188 in the amounts described in step (1) in sequence. The inclusion temperature is 60° C., the reaction speed is 1000 rpm, and the inclusion time is 8 h.

[0077] (3) spray drying the prepared inclusion compound solution to obtain a white inclusion compound powder, wherein the inlet air temperature of the spray drying is 190°C, the outlet air temperature is 90°C, and the atomizing disk speed is 3200 r / min;

[0078] (4) The product was placed in a high-temperature forced air drying oven to remove acetic acid at high temperature. The drying oven temperature was 130°C and the drying time was 4 hours.

[0079] (5) Grind the dried product through an 80-mesh sieve;

[0080] (6) The sieved product was mixed with 62.5 g of sulfachloropyridazine sodium and 25 g of maltodextrin to obtain soluble compound sulfachloropyridazine sodium powder.

[0081] The soluble compound sulfachloropyridazine sodium powder prepared in this example is a dry, loose, uniformly mixed, light yellow powder of uniform color, which passes through an 80-mesh sieve. The solubility of trimethoprim in the powder can reach 2300 ppm.

[0082] The samples prepared in the above examples are tested below.

[0083] 1. Quality evaluation of trimethoprim inclusion complex

[0084] 1. Determine the UV detection wavelength

[0085] Referring to the absorption coefficient section of trimethoprim in the 2020 edition of the "Pharmacopoeia of the People's Republic of China", its ultraviolet detection wavelength is determined to be 271nm, which can be used for HPLC detection.

[0086] 2. Drawing a standard curve using UV spectrophotometer

[0087] The trimethoprim standard solution was diluted stepwise with methanol to prepare trimethoprim solutions with concentrations of 2.775, 5.55, 11.1, 22.2, and 44.4 μg / ml, and the absorbance was measured at a wavelength of 271 nm.

[0088] Methanol was used as a blank control, trimethoprim concentration (C) was used as the abscissa, and absorbance (A) was used as the ordinate. A standard curve was drawn and linear regression was performed.

[0089] The results are as follows:

[0090] Table 1. Results of trimethoprim UV spectrophotometer test

[0091]

[0092]

[0093] Figure 1 The standard curve of trimethoprim UV spectrophotometer was established based on concentration and absorbance. Its regression equation is: C = 0.0213A + 0.0119, R 2 =0.9996, where C is the concentration of trimethoprim and A is the absorbance.

[0094] 3. Detection of trimethoprim content in the prepared inclusion complex

[0095] Three groups of inclusion complex solutions were prepared in parallel with the recipe and process of Example 2. The actual content of trimethoprim in the inclusion complex was calculated using the calibration curve established in 2. The results are shown in the following table:

[0096] Table 2 Actual content of trimethoprim in inclusion complex

[0097] serial number Actual concentration (μg / ml) Theoretical concentration (μg / ml) percentage Example 2-1 38.79 40 96.97％ Example 2-2 40.17 40 100.4％ Example 2-3 39.89 40 99.73％

[0098] From the above results, it can be seen that the formulation and process of the present invention can effectively include trimethoprim.

[0099] 2. Quality Evaluation of Soluble Compound Sulfadiazine Sodium Powder

[0100] 1. Content Determination

[0101] The experiment was designed with reference to the content determination method of compound sulfachloropyridazine sodium powder in the 2020 edition of the Veterinary Pharmacopoeia of the People's Republic of China. Take an appropriate amount of this product (approximately equivalent to 0.2g of sulfachloropyridazine sodium and 40mg of trimethoprim), accurately weigh it, place it in a 100mL volumetric flask, add 50% methanol solution to dissolve it and dilute it to the scale, shake it well; accurately measure 5mL, place it in a 50mL volumetric flask, dilute it to the scale with mobile phase, shake it well; accurately measure 20uL, inject it into the liquid chromatograph, and record the liquid chromatogram; take another sulfachloropyridazine sodium reference substance and trimethoprim reference substance and determine them in the same way. Calculate by peak area according to the external standard method to obtain the result.

[0102] The results are as follows:

[0103] Table 3 Content determination and mass ratio results

[0104] Sulfadiazine sodium (μg / mL) Trimethoprim (μg / mL) Concentration ratio Example 1 189.44 38.98 4.86 Example 2 205.32 41.23 4.98 Example 3 195.47 39.73 4.92

[0105] As can be seen from the above table, the content determination results of the prepared samples meet the quality standards, and the content ratio of sulfachloropyridazine sodium to trimethoprim in the samples meets the requirements.

[0106] 2. Loss on drying

[0107] The drying loss of the soluble compound sulfachloropyridazine sodium powder prepared in Example 2 was measured with reference to Appendix 135 of the 2015 edition of the Veterinary Pharmacopoeia of the People's Republic of China.

[0108] Experimental results: The drying loss was 1.13% ± 0.05%.

[0109] Experimental conclusion: less than 2%, meeting the testing standards of the Veterinary Pharmacopoeia.

[0110] 3. Moisture determination

[0111] The water activity agent was used to measure the water content of the soluble compound sulfachloropyridazine sodium powder prepared in Example 2.

[0112] Experimental results: The moisture content was determined to be 2.03%.

[0113] Experimental conclusion: less than 3%, meeting the testing standards of the Veterinary Pharmacopoeia.

[0114] 4. Stability inspection

[0115] The stability of the soluble compound sulfachloropyridazine sodium powder prepared by the present invention is compared with that of the commercially available product Danan within 12 hours.

[0116] The experimental group was 3 groups of soluble compound sulfachloropyridazine sodium powder prepared in parallel according to Experimental Example 2, and the control group was a commercially available sulfachloropyridazine sodium product.

[0117] Experimental method: Take an appropriate amount of the soluble compound sulfachloropyridazine sodium powder prepared in Example 2 and dissolve it (TMP solubility is about 3000 ppm). At the same time, take an appropriate amount of a commercially available sulfachloropyridazine sodium product and dissolve it (its solubility is much lower than that of the experimental group) to examine the stability of the sample solution within 12 hours.

[0118] The results are as follows:

[0119] Table 4 Comparison of the stability of the soluble sulfachloropyridazine sodium powder prepared by the present invention and the commercially available product solution

[0120] control group Example 2-1 Example 2-2 Example 2-3 0h Light yellow, no precipitation Yellow, no precipitation Yellow, no precipitation Yellow, no precipitation 0.5h Light yellow, a small amount of precipitation Yellow, no precipitation Yellow, no precipitation Yellow, no precipitation 1h Obvious stratification, with a large amount of sediment at the bottom Yellow, no precipitation Yellow, no precipitation Yellow, no precipitation 2h - Yellow, no precipitation Yellow, no precipitation Yellow, no precipitation 3h - Yellow, no precipitation Yellow, no precipitation Yellow, no precipitation 4h - Yellow, no precipitation Yellow, no precipitation Yellow, no precipitation 8h - Yellow, no precipitation Yellow, no precipitation Yellow, no precipitation 12h - Yellow, no precipitation Yellow, with a small amount of precipitation Yellow, with a small amount of precipitation

[0121] From the above results and Figure 2 It can be seen that the sample prepared in Example 2 can maintain good stability within 12 hours, and a small amount of precipitation will be produced between 11 and 12 hours. The control group begins to stratify at 0.5 hours, and its color is lighter. The content of sulfachloropyridazine sodium and trimethoprim are much lower than those in the experimental group.

Claims

1. A soluble compound sulfachloropyridazine sodium powder, characterized in that, The invention comprises sulfachloropyridazine sodium, trimethoprim inclusion compound and filler, wherein the mass ratio of sulfachloropyridazine sodium, trimethoprim inclusion compound and filler is 62.5:12.5:

25.

2. The soluble compound sulfachloropyridazine sodium powder according to claim 1, characterized in that The trimethoprim inclusion compound is prepared from trimethoprim, a cyclodextrin derivative, a stabilizer and a surfactant, and the mass ratio of the trimethoprim, the cyclodextrin derivative, the stabilizer and the surfactant is 12.5-25:25-100:3-5:1-3.

3. The soluble compound sulfachloropyridazine sodium powder according to claim 2, characterized in that, The cyclodextrin derivative is one or a combination of β-cyclodextrin, methyl-β-cyclodextrin, carboxymethyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, and hydroxypropyl-γ-cyclodextrin; the stabilizer is povidone K30 or povidone K90; and the surfactant is one or a combination of Tween 60, Tween 80, and poloxamer 188.

4. The soluble compound sulfachloropyridazine sodium powder according to claim 2, characterized in that, The preparation method of the trimethoprim inclusion compound is as follows: trimethoprim, a cyclodextrin derivative, a stabilizer and a surfactant are added into an acetic acid solution for inclusion, and the inclusion compound solution is dried to obtain the trimethoprim inclusion compound.

5. The soluble compound sulfachloropyridazine sodium powder according to claim 4, characterized in that, The preparation process of inclusion is: inclusion temperature 60°C-80°C, stirring speed 900-1500 r / min, and reaction time 4-8 h.

6. The soluble compound sulfachloropyridazine sodium powder according to claim 4, characterized in that: The inclusion compound solution is firstly subjected to spray drying to obtain an inclusion compound solid, which is then placed in a drying oven for further drying to obtain a trimethoprim inclusion compound.

7. The soluble compound sulfachloropyridazine sodium powder according to claim 1, characterized in that: The filler is one or a combination of sucralose, maltodextrin and sucrose.

8. The method for preparing the soluble compound sulfachloropyridazine sodium powder according to any one of claims 1 to 7, characterized in that: The trimethoprim inclusion compound, sulfachloropyridazine sodium and a filler are mixed to obtain the soluble compound sulfachloropyridazine sodium powder.

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