CN-122005463-A - Compound sulfachloropyrazine sodium soluble powder and preparation method and application thereof

Abstract

The application discloses compound sulfachloropyrazine sodium soluble powder and a preparation method and application thereof, and belongs to the technical field of veterinary medicines. The soluble powder comprises sulfachloropyrazine sodium 15-30 g, methicillin 4-8 g, carrier I6-12 g, carrier II 3-6 g, surfactant, metal chelating agent, antioxidant and filler. The preparation method is characterized in that the carrier I and the carrier II are dissolved in absolute ethyl alcohol, then the carrier II is added for dispersion, and the carrier I and the carrier II are heated for volatilization, cooled for solidification and dried to prepare the carrier solid dispersion of the composite carrier of the methicillin, and then the carrier solid dispersion of the composite carrier of the methicillin is mixed with sulfachloropyrazine sodium and other auxiliary materials to prepare the finished product. The application obviously improves the dissolving and dispersing performance of the methicillin by a solid dispersion technology, ensures synchronous dissolution of the methicillin and the sulfachloropyrazine sodium, ensures that the preparation has good water solubility and high stability, and shows excellent synergistic effect and animal growth promoting effect in preventing and treating chicken and sheep coccidiosis.

Inventors

• HUANG LINGLI
• LIU HAIYAN
• ZHANG RONG
• OU YAHONG
• ZHANG HEYING
• PAN YUANHU

Assignees

• 华中农业大学

Dates

Publication Date

20260512

Application Date

20260408

Claims (10)

1. 1. A compound sulfachloropyrazine sodium soluble powder, wherein each 100 g of the soluble powder consists of the following components: 15-30 g of sulfachloropyrazine sodium, 4-8 g of methine, 6-12 g of carrier I, 3-6 g of carrier II, 1-5 g of surfactant, 0.1-3 g of metal chelating agent, 0.1-3 g of antioxidant and the balance of filler, wherein the carrier I is polyvinylpyrrolidone-vinyl acetate copolymer or polyvinylpyrrolidone K30, and the carrier II is mesoporous silica.
2. 2. The compound sulfachloropyrazine sodium soluble powder according to claim 1, wherein each 100 g of the soluble powder consists of 18-25 g of sulfachloropyrazine sodium, 4-5 g of methine, 6-8 g of carrier I, 3-4 g of carrier II, 2.5-3 g of surfactant, 0.3-2 g of metal chelating agent, 0.3-2 g of antioxidant and the balance of filler.
3. 3. The compound sulfachloropyrazine sodium soluble powder according to claim 1, wherein the surfactant is at least one selected from sodium dodecyl sulfate, tween 80 and poloxamer 188, and the metal chelating agent is disodium edentate.
4. 4. The compound sulfachloropyrazine sodium soluble powder according to claim 1, wherein the antioxidant is at least one of anhydrous sodium sulfite and sodium thiosulfate, and the filler is at least one of anhydrous glucose and lactose.
5. 5. The method for preparing the compound sulfachloropyrazine sodium soluble powder of claim 1, comprising the following steps: (1) Dissolving the copolymer of the methicillin and the polyvinylpyrrolidone-vinyl acetate or the polyvinylpyrrolidone K30 in absolute ethyl alcohol, adding mesoporous silica and uniformly dispersing to form a uniform dispersion system of the methicillin loaded on a composite carrier; (2) Heating the system obtained in the step (1) to 70-85 ℃, and stirring and volatilizing to remove the solvent until a sticky substance is formed; (3) Spreading the sticky material into a thin layer, and performing cooling and solidifying treatment; (4) Drying the solidified material to constant weight, crushing the solidified material to 80-100 meshes, and sieving the crushed material to obtain a methine solid dispersion; (5) Uniformly mixing sulfachloropyrazine sodium, the methine solid dispersion obtained in the step (4), the surfactant, the metal chelating agent, the antioxidant and the filler according to the claim 1; (6) And (3) grinding and sieving the mixture obtained in the step (5) to obtain a finished product of the compound sulfachloropyrazine sodium soluble powder.
6. 6. The process according to claim 5, wherein in the step (3), the cooling and solidifying treatment is carried out under the condition that the relative humidity is not higher than 40%, at 0℃for 4 to 8 hours.
7. 7. Use of the compound sulfachloropyrazine sodium soluble powder according to any one of claims 1 to 4 in preparing a medicament for preventing and treating coccidiosis in livestock and poultry.
8. 8. The use according to claim 7, wherein the livestock and poultry are chickens or sheep.
9. 9. The use according to claim 8, wherein the chicken is a chick and the sheep is a lamb.
10. 10. The use according to any one of claims 7-9, wherein the coccidiosis is a coccidiosis caused by eimeria tenella or eimeria ovis.

Description

Compound sulfachloropyrazine sodium soluble powder and preparation method and application thereof Technical Field The application relates to the technical field of veterinary medicines, in particular to compound sulfachloropyrazine sodium soluble powder, a preparation method and application thereof, and more particularly relates to a compound anticoccidial veterinary medicine preparation for improving dispersibility and solubility of a synergist in a compound preparation by introducing an amorphous solid dispersion of methicillin. Background Coccidiosis is a common and serious parasitic disease caused by Eimeria (Eimeria) protozoa, and is widely circulated in livestock and poultry cultivation. Chicken coccidiosis is one of the most serious diseases in chicken raising industry, and especially has great influence on chickens, can cause serious growth blockage and extremely high acute infection mortality rate, and causes great economic loss. Also, coccidiosis in sheep is common worldwide, clinical symptoms are obvious after lamb infection, diarrhea, growth retardation and other problems are caused, and the damage is increasingly prominent along with the turning of the breeding mode to large-scale house feeding. At present, chemical drug control remains the primary means of controlling the disease. Sulfachloropyrazine sodium (Sulfachloropyrazine sodium, SPZ) is used as a special animal sulfanilamide anticoccidial drug, and plays a role by interfering with the metabolism of coccidian folic acid, so that the sulfachloropyrazine sodium has wide clinical application. However, with the long-term and wide-ranging use of medicines, the drug resistance of coccidium to sulfachloropyrazine sodium is increasingly prominent, the control effect of single-component preparations is gradually limited, and the requirements of high-efficiency control in the current cultivation production are difficult to meet. In order to improve the curative effect and delay drug resistance, the sulfonamide and the antibacterial synergist are commonly used in clinical practice, and the synergistic effect is generated by doubly blocking the folic acid metabolic pathway. The methicillin (Aditoprim, ADP) is a novel benzyl aminopyrimidine synergist, and has the pharmacokinetic advantages of long half-life, high bioavailability and the like compared with traditional benzyl aminopyrimidine medicines such as trimethoprim, omeprazole, bromine Mo Pulin and the like, and has the potential of enhancing anticoccidial activity when being combined with sulfachloropyrazine sodium. However, the water solubility of the methicillin itself is extremely poor, which presents a significant challenge for its use in compound formulations. In the existing compound anticoccidial soluble powder preparation, a preparation process of simply and physically mixing sulfachloropyrazine sodium and methicillin bulk drugs is mostly adopted. Because of the great difference of physical and chemical properties, sulfachloropyrazine sodium is easy to dissolve, and the methicillin is difficult to dissolve. This simple mixing approach makes it difficult to ensure that the two active ingredients are simultaneously and evenly dispersed during dissolution. After administration, the soluble components are rapidly dissolved, and the insoluble components are retained in the gastrointestinal tract, so that the concentration of the in-vivo medicines is asynchronous, the optimal sequential blocking effect can not be realized, and the full play of the synergistic effect of the compound is severely restricted. In addition, uneven dispersion of poorly soluble ingredients may also affect the content uniformity of the formulation and the accuracy of the dosage administered. Solid dispersion technology is one of the effective strategies for improving the dissolution rate of poorly soluble drugs by highly dispersing the drug in a hydrophilic carrier, in an amorphous state, thereby increasing the dissolution rate and extent. Although the technology is known per se, how to apply the technology to solve the problem of the dissolution synergy of the methicillin and the sulfachloropyrazine sodium in the compound preparation in a targeted manner, and design a specific compound carrier system and technology which have good stability and are suitable for industrial production, and a systematic solution is not yet available in the prior art. Therefore, development of a novel compound sulfachloropyrazine sodium soluble powder and a preparation method thereof is needed, the dispersion state and the dissolution performance of the methicillin in the preparation can be fundamentally improved, synchronous dissolution and synergistic effect of the methicillin in the preparation are ensured, and the overall anticoccidial effect and the application value of the compound preparation are improved. Disclosure of Invention The application relates to a compound sulfachloropyrazine sodium soluble powder, a preparation method