Microencapsulated tilmicosin premix and preparation method thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, and particularly discloses a microencapsulated tilmicosin premix and a preparation method thereof, and the microencapsulated tilmicosin premix comprises the following raw materials: tilmicosin, a composite capsule material, an emulsifier, a stabilizer, a suspending aid and livestock and poultry feed acceptable auxiliary materials. The preparation method of the microencapsulated tilmicosin premix comprises the following steps: step 1, adding a composite capsule material into deionized water, and stirring and dispersing to obtain a capsule material solution; step 2, adding tilmicosin, an emulsifier and a stabilizer into the capsule material solution, and homogenizing to obtain a medicine dispersion liquid; step 3, performing spray drying on the medicine dispersion liquid, and sieving after drying to obtain microcapsule particles; and step 4, adding the microcapsule particles, a suspending aid and livestock and poultry feed acceptable auxiliary materials into a mixing machine, and mixing to obtain the microencapsulated tilmicosin premix. The prepared microencapsulated tilmicosin premix is high in encapsulation efficiency, excellent in targeting performance and high in stability, and adapts to livestock and poultry feed application scenes.

Description

Technical Field

[0001] This application relates to the field of pharmaceutical formulation technology, and more specifically, to a microencapsulated tilmicosin premix and its preparation method. Background Technology

[0002] Tilmicosin is a semi-synthetic macrolide antibiotic specifically for livestock and poultry. Due to its excellent inhibitory activity against pathogenic bacteria such as Gram-positive bacteria, some Gram-negative bacteria, mycoplasma, and spirochetes, it is widely used in livestock and poultry farming. It is particularly effective in preventing and treating pneumonia in livestock caused by Actinobacillus pleuropneumoniae and Pasteurella multocida, as well as mycoplasma infections in avian animals and mastitis in lactating animals. Recent studies have also found that it has a certain inhibitory effect on porcine reproductive and respiratory syndrome (PRRS), indicating a broad market application prospect.

[0003] However, tilmicosin's inherent characteristics and existing formulation technologies have many shortcomings that severely limit its application efficacy: First, its palatability is extremely poor. Tilmicosin has a strong bitter taste and a distinctive odor. When fed as a conventional premix, it easily leads to livestock and poultry refusing to eat, reduced feed intake, and even vomiting and other stress reactions, directly affecting medication adherence. Second, its stability is poor. Tilmicosin is chemically unstable and sensitive to light, heat, and acidic environments. It is easily degraded and ineffective during storage, and after entering the stomach of livestock and poultry, it is destroyed by gastric acid, reducing bioavailability. Third, the coating technology is imperfect. Existing microencapsulation technologies mostly use single-layer coating or... Simple double-layer coating, such as an acrylic resin outer coating and starch inner coating, can partially mask the taste, but the coating is easily damaged during transportation or chewing, and the sustained-release effect is poor, failing to achieve precise drug release in the intestine. Some technologies use fatty acids, paraffin, etc. as core excipients, which can improve palatability, but the drug release rate is difficult to control, and the problem of excessive fluctuations in blood drug concentration is likely to occur. Fourth, the preparation process is complex. The preparation of some existing microcapsules requires multiple processes such as soft material preparation, extrusion and spheroidization, and multiple fluidized bed drying. The process is cumbersome, the production cost is high, and the product mixing uniformity is poor, making it unsuitable for large-scale industrial production.

[0004] To address the aforementioned issues, there is an urgent need to develop a novel microencapsulated tilmicosin premix to achieve the technical goals of thorough taste masking, improved stability, excellent sustained-release performance, and simple processing, thereby resolving the core pain points of existing formulations. Summary of the Invention

[0005] To address the technical problems mentioned in the background section, this application provides a microencapsulated tilmicosin premix and its preparation method.

[0006] In a first aspect, this application provides a microencapsulated tilmicosin premix, employing the following technical solution: A microencapsulated tilmicosin premix comprises the following raw materials by weight percentage: tilmicosin 5-20%, composite encapsulation material 30-40%, emulsifier 2-8%, stabilizer 1-5%, suspending agent 5-15%, and the balance being acceptable excipients for livestock and poultry feed.

[0007] Preferably, the composite capsule material is a mixture of a ternary compound and a functional component.

[0008] Preferably, the ternary compound is a compound of sodium octenyl succinate starch, maltodextrin, and acrylic resin.

[0009] Preferably, the mass ratio of sodium octenyl succinate starch, maltodextrin, and acrylic resin in the ternary compound is 10-20:10-15:1-3.

[0010] Preferably, the acrylic resin is acrylic resin L30D-55.

[0011] Preferably, the functional component consists of low-methoxyl pectin and lactoferrin in a mass ratio of 1-1.5:0.3-0.8.

[0012] Preferably, the mass ratio of the ternary compound to the functional component in the composite capsule material is 10-12:2-5.

[0013] Preferably, the emulsifier consists of Tween 80 and Span 80 in a mass ratio of 2-5:1-2.

[0014] Preferably, the stabilizer is composed of a compound of vitamin E and citric acid in a mass ratio of 3-5:1.

[0015] Preferably, the suspending agent is soluble starch or sodium carboxymethyl cellulose.

[0016] Preferably, the livestock and poultry feed may accept one or more of the following as adjuvants: lactose, corn starch, and wheat bran.

[0017] Secondly, this application provides a method for preparing a microencapsulated tilmicosin premix, using the following technical solution: A method for preparing a microencapsulated tilmicosin premix includes the following preparation steps: Step 1: Add the composite capsule material to deionized water, stir and disperse at 60-70℃ for 20-30 minutes, and cool to room temperature to obtain the capsule material solution; Step 2: Add tilmicosin, emulsifier and stabilizer to the capsule material solution, homogenize for 5-10 minutes to obtain drug dispersion; Step 3: Spray dry the drug dispersion, and then sieve it to obtain microcapsule particles; Step 4: Add the microcapsule particles, suspending agent and acceptable feed additives to the mixer and mix for 10-15 minutes to obtain microencapsulated tilmicosin premix.

[0018] Preferably, in step 3, the inlet air temperature for spray drying is 180-220℃, and the outlet air temperature is 80-100℃.

[0019] In summary, this application has the following beneficial effects: This application employs a ternary compound composed of sodium octenyl succinate starch, maltodextrin, and acrylic resin L30D-55 to form a dual structure of "emulsification and encapsulation-film-forming reinforcement." The hydrophobic groups of sodium octenyl succinate starch are highly compatible with the lipid-soluble tilmicosin, significantly improving drug dispersion uniformity and encapsulation efficiency, resulting in a significant increase in microcapsule encapsulation rate. This effectively reduces leakage of tilmicosin during storage and processing, while ensuring uniform microcapsule particle size after spray drying, thus guaranteeing the consistent and stable quality of the premix product. The acrylic resin L30D-55 in the encapsulation material possesses excellent water dispersibility and pH sensitivity, enabling targeted release into the digestive tract of livestock and poultry: maintaining capsule stability in the acidic environment of the stomach, reducing the risk of drug leakage and degradation; and efficiently dissolving and releasing in the neutral / weakly alkaline environment of the intestine, perfectly matching the digestive physiology of livestock and poultry, and significantly improving the bioavailability of tilmicosin. The functional components are a combination of low-methoxyl pectin and lactoferrin. The two form stable composite particles through electrostatic interaction, which further enhances the density of the capsule and improves the encapsulation rate of tilmicosin. At the same time, lactoferrin and tilmicosin form a synergistic antibacterial effect, broadening the inhibition range against pathogenic bacteria in the respiratory and digestive tracts of livestock and poultry, and significantly enhancing the clinical application effect. Detailed Implementation

[0020] The present application will be further described in detail below with reference to the embodiments.

[0021] Sodium octenyl succinate starch and hydroxypropyl starch phosphate used in the embodiments and comparative examples of this application were purchased from Qingdao Haiweisen Biotechnology Co., Ltd.; maltodextrin was purchased from Zhejiang Yicun Biotechnology Co., Ltd.; acrylic resin L30D-55 and acrylic resin L100 were both purchased from Shanghai Dexiang Pharmaceutical Technology Co., Ltd.; low methoxy pectin was purchased from Qiyuan (Guangdong) Pharmaceutical Chemical Co., Ltd.; lactoferrin was purchased from Jiangsu Jiujia Biotechnology Co., Ltd.; soluble starch was purchased from Shanghai Quanyan Biotechnology Co., Ltd.; and wheat bran powder was purchased from Jiangsu Jichao Biotechnology Co., Ltd.

[0022] Examples 1-3 provide a microencapsulated tilmicosin premix and its preparation method.

[0023] Example 1 A microencapsulated tilmicosin premix comprises the following raw materials in weight percentages: 5% tilmicosin, 30% composite encapsulation material, 2% emulsifier, 1% stabilizer, 5% suspending agent, and the balance being livestock and poultry feed-acceptable excipients. The emulsifier consists of Tween 80 and Span 80 in a mass ratio of 2:1; the stabilizer consists of vitamin E and citric acid in a mass ratio of 3:1; the suspending agent is soluble starch; the livestock and poultry feed-acceptable excipient is wheat bran powder; the composite encapsulation material consists of a ternary compound and functional components in a mass ratio of 10:2; the ternary compound contains sodium octenyl succinate starch, maltodextrin, and acrylic resin L30D-55 in a mass ratio of 10:10:1; and the functional components consist of low-methoxyl pectin and lactoferrin in a mass ratio of 1:0.3.

[0024] A method for preparing a microencapsulated tilmicosin premix includes the following preparation steps: Step 1: Add the composite capsule material to deionized water, control the solid-liquid mass ratio of the composite capsule material to the deionized water to be 1:10, stir and disperse at 60℃ and 400 rpm for 20 min, cool to room temperature to obtain the capsule material solution. Step 2: Add tilmicosin, emulsifier and stabilizer to the capsule material solution, and homogenize it for 5 minutes at 3000 rpm using a high-speed homogenizer to obtain a drug dispersion. Step 3: Spray dry the drug dispersion, controlling the inlet air temperature to 180℃ and the outlet air temperature to 80℃. After drying, sieve through a 200-mesh sieve to obtain microcapsule particles. Step 4: Add the microcapsule particles, suspending agent and livestock feed acceptable excipients into the mixer and mix at 300 rpm for 10 minutes to obtain microencapsulated tilmicosin premix.

[0025] Example 2 A microencapsulated tilmicosin premix comprises the following raw materials in weight percentages: 12% tilmicosin, 35% composite encapsulation material, 5% emulsifier, 3% stabilizer, 10% suspending agent, and the balance being livestock and poultry feed-acceptable excipients. The emulsifier consists of Tween 80 and Span 80 in a mass ratio of 4:1.5; the stabilizer consists of vitamin E and citric acid in a mass ratio of 4:1; the suspending agent is soluble starch; the livestock and poultry feed-acceptable excipient is wheat bran; the composite encapsulation material consists of a ternary compound and functional components in a mass ratio of 11:4; the ternary compound contains sodium octenyl succinate starch, maltodextrin, and acrylic resin L30D-55 in a mass ratio of 15:12:2; and the functional components consist of low-methoxyl pectin and lactoferrin in a mass ratio of 1.2:0.5.

[0026] A method for preparing a microencapsulated tilmicosin premix includes the following preparation steps: Step 1: Add the composite capsule material to deionized water, control the solid-liquid mass ratio of the composite capsule material to the deionized water to be 2:11, stir and disperse at 65℃ and a stirring speed of 500 rpm for 25 minutes, and cool to room temperature to obtain the capsule material solution. Step 2: Add tilmicosin, emulsifier and stabilizer to the capsule material solution, and homogenize it using a high-speed homogenizer at 4000 rpm for 8 min to obtain a drug dispersion. Step 3: Spray dry the drug dispersion, controlling the inlet air temperature to 200℃ and the outlet air temperature to 90℃. After drying, sieve through a 250-mesh sieve to obtain microcapsule particles. Step 4: Add the microcapsule particles, suspending agent and livestock feed acceptable excipients into the mixer and mix at 400 rpm for 12 minutes to obtain microencapsulated tilmicosin premix.

[0027] Example 3 A microencapsulated tilmicosin premix comprises the following raw materials in weight percentages: 20% tilmicosin, 40% composite encapsulation material, 8% emulsifier, 5% stabilizer, 15% suspending agent, and the balance being livestock and poultry feed-acceptable excipients. The emulsifier consists of Tween 80 and Span 80 in a mass ratio of 5:2; the stabilizer consists of vitamin E and citric acid in a mass ratio of 5:1; the suspending agent is soluble starch; the livestock and poultry feed-acceptable excipient is wheat bran; the composite encapsulation material consists of a ternary compound and functional components in a mass ratio of 12:5; the ternary compound contains sodium octenyl succinate starch, maltodextrin, and acrylic resin L30D-55 in a mass ratio of 20:15:3; and the functional components consist of low-methoxyl pectin and lactoferrin in a mass ratio of 1.5:0.8.

[0028] A method for preparing a microencapsulated tilmicosin premix includes the following preparation steps: Step 1: Add the composite capsule material to deionized water, control the solid-liquid mass ratio of the composite capsule material to the deionized water to be 3:12, stir and disperse at 70℃ and 600 rpm for 30 min, cool to room temperature to obtain the capsule material solution. Step 2: Add tilmicosin, emulsifier and stabilizer to the capsule material solution, and homogenize it for 10 min at 5000 rpm using a high-speed homogenizer to obtain a drug dispersion. Step 3: Spray dry the drug dispersion, controlling the inlet air temperature to 220℃ and the outlet air temperature to 100℃. After drying, sieve through a 300-mesh sieve to obtain microcapsule particles. Step 4: Add the microcapsule particles, suspending agent and livestock feed acceptable excipients into the mixer and mix at 500 rpm for 15 minutes to obtain microencapsulated tilmicosin premix.

[0029] Comparative Example 1 A microencapsulated tilmicosin premix comprises the following raw materials in weight percentages: 5% tilmicosin, 30% composite encapsulation material, 2% emulsifier, 1% stabilizer, 5% suspending agent, and the balance being livestock and poultry feed-acceptable excipients. The emulsifier consists of Tween 80 and Span 80 in a mass ratio of 2:1; the stabilizer consists of vitamin E and citric acid in a mass ratio of 3:1; the suspending agent is soluble starch; the livestock and poultry feed-acceptable excipient is wheat bran; the composite encapsulation material consists of a ternary compound and functional components in a mass ratio of 10:2; the ternary compound contains hydroxypropyl starch phosphate, maltodextrin, and acrylic resin L30D-55 in a mass ratio of 10:10:1; and the functional components consist of low-methoxyl pectin and lactoferrin in a mass ratio of 1:0.3.

[0030] A method for preparing a microencapsulated tilmicosin premix includes the following preparation steps: Step 1: Add the composite capsule material to deionized water, control the solid-liquid mass ratio of the composite capsule material to the deionized water to be 1:10, stir and disperse at 60℃ and 400 rpm for 20 min, cool to room temperature to obtain the capsule material solution. Step 2: Add tilmicosin, emulsifier and stabilizer to the capsule material solution, and homogenize it for 5 minutes at 3000 rpm using a high-speed homogenizer to obtain a drug dispersion. Step 3: Spray dry the drug dispersion, controlling the inlet air temperature to 180℃ and the outlet air temperature to 80℃. After drying, sieve through a 200-mesh sieve to obtain microcapsule particles. Step 4: Add the microcapsule particles, suspending agent and livestock feed acceptable excipients into the mixer and mix at 300 rpm for 10 minutes to obtain microencapsulated tilmicosin premix.

[0031] Comparative Example 2 A microencapsulated tilmicosin premix comprises the following raw materials in weight percentages: 5% tilmicosin, 30% composite encapsulation material, 2% emulsifier, 1% stabilizer, 5% suspending agent, and the balance being livestock and poultry feed-acceptable excipients. The emulsifier consists of Tween 80 and Span 80 in a mass ratio of 2:1; the stabilizer consists of vitamin E and citric acid in a mass ratio of 3:1; the suspending agent is soluble starch; the livestock and poultry feed-acceptable excipient is wheat bran; the composite encapsulation material consists of a binary compound and a functional component in a mass ratio of 10:2; the binary compound contains maltodextrin and acrylic resin L30D-55 in a mass ratio of 10:1; and the functional component consists of low-methoxyl pectin and lactoferrin in a mass ratio of 1:0.3.

[0032] A method for preparing a microencapsulated tilmicosin premix includes the following preparation steps: Step 1: Add the composite capsule material to deionized water, control the solid-liquid mass ratio of the composite capsule material to the deionized water to be 1:10, stir and disperse at 60℃ and 400 rpm for 20 min, cool to room temperature to obtain the capsule material solution. Step 2: Add tilmicosin, emulsifier and stabilizer to the capsule material solution, and homogenize it for 5 minutes at 3000 rpm using a high-speed homogenizer to obtain a drug dispersion. Step 3: Spray dry the drug dispersion, controlling the inlet air temperature to 180℃ and the outlet air temperature to 80℃. After drying, sieve through a 200-mesh sieve to obtain microcapsule particles. Step 4: Add the microcapsule particles, suspending agent and livestock feed acceptable excipients into the mixer and mix at 300 rpm for 10 minutes to obtain microencapsulated tilmicosin premix.

[0033] Comparative Example 3 A microencapsulated tilmicosin premix comprises the following raw materials in weight percentages: 5% tilmicosin, 30% composite encapsulation material, 2% emulsifier, 1% stabilizer, 5% suspending agent, and the balance being livestock and poultry feed-acceptable excipients. The emulsifier consists of Tween 80 and Span 80 in a mass ratio of 2:1; the stabilizer consists of vitamin E and citric acid in a mass ratio of 3:1; the suspending agent is soluble starch; the livestock and poultry feed-acceptable excipient is wheat bran; the composite encapsulation material consists of a binary compound and a functional component in a mass ratio of 10:2; the binary compound contains sodium octenyl succinate starch and maltodextrin in a mass ratio of 1:1; and the functional component consists of low-methoxyl pectin and lactoferrin in a mass ratio of 1:0.3.

[0034] A method for preparing a microencapsulated tilmicosin premix includes the following preparation steps: Step 1: Add the composite capsule material to deionized water, control the solid-liquid mass ratio of the composite capsule material to the deionized water to be 1:10, stir and disperse at 60℃ and 400 rpm for 20 min, cool to room temperature to obtain the capsule material solution. Step 2: Add tilmicosin, emulsifier and stabilizer to the capsule material solution, and homogenize it for 5 minutes at 3000 rpm using a high-speed homogenizer to obtain a drug dispersion. Step 3: Spray dry the drug dispersion, controlling the inlet air temperature to 180℃ and the outlet air temperature to 80℃. After drying, sieve through a 200-mesh sieve to obtain microcapsule particles. Step 4: Add the microcapsule particles, suspending agent and livestock feed acceptable excipients into the mixer and mix at 300 rpm for 10 minutes to obtain microencapsulated tilmicosin premix.

[0035] Comparative Example 4 A microencapsulated tilmicosin premix comprises the following raw materials in weight percentages: 5% tilmicosin, 30% composite encapsulation material, 2% emulsifier, 1% stabilizer, 5% suspending agent, and the balance being livestock and poultry feed-acceptable excipients. The emulsifier consists of Tween 80 and Span 80 in a mass ratio of 2:1; the stabilizer consists of vitamin E and citric acid in a mass ratio of 3:1; the suspending agent is soluble starch; the livestock and poultry feed-acceptable excipient is wheat bran; the composite encapsulation material consists of a ternary compound and functional components in a mass ratio of 10:2; the ternary compound contains sodium octenyl succinate starch, maltodextrin, and acrylic resin L100 in a mass ratio of 10:10:1; and the functional components consist of low-methoxyl pectin and lactoferrin in a mass ratio of 1:0.3.

[0036] A method for preparing a microencapsulated tilmicosin premix includes the following preparation steps: Step 1: Add the composite capsule material to deionized water, control the solid-liquid mass ratio of the composite capsule material to the deionized water to be 1:10, stir and disperse at 60℃ and 400 rpm for 20 min, cool to room temperature to obtain the capsule material solution. Step 2: Add tilmicosin, emulsifier and stabilizer to the capsule material solution, and homogenize it for 5 minutes at 3000 rpm using a high-speed homogenizer to obtain a drug dispersion. Step 3: Spray dry the drug dispersion, controlling the inlet air temperature to 180℃ and the outlet air temperature to 80℃. After drying, sieve through a 200-mesh sieve to obtain microcapsule particles. Step 4: Add the microcapsule particles, suspending agent and livestock feed acceptable excipients into the mixer and mix at 300 rpm for 10 minutes to obtain microencapsulated tilmicosin premix.

[0037] Comparative Example 5 A microencapsulated tilmicosin premix comprises the following raw materials by weight percentage: 5% tilmicosin, 30% composite encapsulation material, 2% emulsifier, 1% stabilizer, 5% suspending agent, and the balance being livestock and poultry feed-acceptable excipients. The emulsifier consists of Tween 80 and Span 80 in a mass ratio of 2:1; the stabilizer consists of vitamin E and citric acid in a mass ratio of 3:1; the suspending agent is soluble starch; the livestock and poultry feed-acceptable excipient is wheat bran powder; the composite encapsulation material consists of a ternary compound and a functional component in a mass ratio of 10:2; the ternary compound contains sodium octenyl succinate starch, maltodextrin, and acrylic resin L30D-55 in a mass ratio of 10:10:1; and the functional component is low-methoxyl pectin.

[0038] A method for preparing a microencapsulated tilmicosin premix includes the following preparation steps: Step 1: Add the composite capsule material to deionized water, control the solid-liquid mass ratio of the composite capsule material to the deionized water to be 1:10, stir and disperse at 60℃ and 400 rpm for 20 min, cool to room temperature to obtain the capsule material solution. Step 2: Add tilmicosin, emulsifier and stabilizer to the capsule material solution, and homogenize it for 5 minutes at 3000 rpm using a high-speed homogenizer to obtain a drug dispersion. Step 3: Spray dry the drug dispersion, controlling the inlet air temperature to 180℃ and the outlet air temperature to 80℃. After drying, sieve through a 200-mesh sieve to obtain microcapsule particles. Step 4: Add the microcapsule particles, suspending agent and livestock feed acceptable excipients into the mixer and mix at 300 rpm for 10 minutes to obtain microencapsulated tilmicosin premix.

[0039] Performance testing The performance of the microencapsulated tilmicosin premixes prepared in Examples 1-3 and Comparative Examples 1-5 of this application was tested, and the specific test contents are as follows: Encapsulation efficiency: Accurately weigh 1.0 g each of the microencapsulated tilmicosin premixes prepared in Examples 1-3 and Comparative Examples 1-5, disperse them in 25 mL of ethanol solution, shake well, then transfer to a 50 mL volumetric flask, add ethanol to dilute to the mark and shake well, filter, filter the filtrate through a 0.45 μm filter membrane to obtain the sample, and detect the tilmicosin concentration (Cfree) of the sample by HPLC; separately take an equal amount of microcapsule particles, break the capsules and determine the total tilmicosin concentration (Ctotal). Encapsulation efficiency EE (%) = (C 总 -C 游离 ) / C 总 ×100%, each sample was measured in triplicate and the average value was taken; In vitro release: Referencing the "Dissolution Test" (paddle method, 50 rpm) in Part IV of the 2020 edition of the Chinese Veterinary Pharmacopoeia, the pH environment of the gastrointestinal tract was simulated. Simulated gastric juice stage: The dissolution medium was hydrochloric acid solution with pH 1.2 (37±0.5℃). 0.5g of premix was added, and 5mL of sample was taken after 2h. After filtration through a filter membrane, the drug release was determined by HPLC. Simulated intestinal fluid stage: After 2 hours, the pH of the dissolution medium was adjusted to 6.8 with phosphate buffer, and the experiment was continued for another 2 hours. Samples were taken and the release amount was determined using the same method. Chemical stability: Referencing the "Guidelines for Veterinary Drug Stability Testing", the moisture absorption rate of the microencapsulated tilmicosin premix was determined after 6 months of storage at 40±2℃ and relative humidity (RH) of 75±5%. The specific results are shown in Table 1.

[0040] Table 1 Performance testing of microencapsulated tilmicosin premixes prepared in Examples 1-3 and Comparative Examples 1-5 As shown in Table 1, the encapsulation efficiency of the microencapsulated tilmicosin premix prepared in this application is as high as 88.6%-91.8%, far superior to the comparative formulations. This is attributed to the synergistic effect of the ternary compound encapsulation material and low-methoxyl pectin-lactoferrin, which effectively reduces drug leakage. The cumulative release rate in gastric juice is ≤11.8%, forming a reliable enteric barrier to prevent drug degradation by gastric acid. The cumulative release rate in intestinal juice is ≥89.2%, ensuring full dissolution and efficacy of the drug. The hygroscopicity is only 2.3-3.1%, demonstrating excellent storage stability and preventing clumping and deterioration. This premix solves the problems of low encapsulation efficiency, poor targeted release, and insufficient stability in traditional formulations. It is suitable for livestock and poultry feed applications, improves drug bioavailability and safety, and possesses outstanding practical value.

[0041] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A microencapsulated tilmicosin premix characterized in that, The raw materials include the following weight percentages: Timicosin 5-20%, compound capsule material 30-40%, emulsifier 2-8%, stabilizer 1-5%, suspension aid 5-15%, and the rest is livestock and poultry feed acceptable adjuvant.

2. The microencapsulated tilmicosin premix of claim 1, wherein, The compound capsule material is a compound of ternary compound and functional component; the ternary compound is a compound of sodium octenyl succinate starch, malt dextrin and acrylic resin.

3. The microencapsulated tilmicosin premix of claim 2, wherein, The mass ratio of sodium octenyl succinate starch, malt dextrin and acrylic resin in the ternary compound is 10-20:10-15:1-3.

4. The microencapsulated tilmicosin premix of claim 2, wherein, The acrylic resin is acrylic resin L30D-55.

5. The microencapsulated tilmicosin premix of claim 2, wherein, The functional component is composed of low methoxyl pectin and lactoferrin with a mass ratio of 1-1.5:0.3-0.8; the mass ratio of ternary compound and functional component in the compound capsule material is 10-12:2-5.

6. The microencapsulated tilmicosin premix of claim 1, wherein, The emulsifier is composed of Tween 80 and Span 80 with a mass ratio of 2-5:1-2.

7. The microencapsulated tilmicosin premix of claim 1, wherein, The stabilizer is composed of vitamin E and citric acid with a mass ratio of 3-5:

1.

8. The microencapsulated tilmicosin premix of claim 1, wherein, The suspension aid is soluble starch or sodium carboxymethyl cellulose; the livestock and poultry feed acceptable adjuvant is one or several of lactose, corn starch and wheat bran powder.

9. A process for the preparation of the microencapsulated tilmicosin premix of any one of claims 1 to 8, characterized in that, The preparation steps include the following: Step 1, add the compound capsule material into deionized water, stir and disperse at 60-70℃ for 20-30min, cool to room temperature to obtain a capsule solution; Step 2, add timicosin, emulsifier and stabilizer into the capsule solution, homogenize for 5-10min to obtain a drug dispersion; Step 3, spray dry the drug dispersion, sieve after drying to obtain micro-capsule particles; Step 4, add the micro-capsule particles, suspension aid and livestock and poultry feed acceptable adjuvant into a mixer, mix for 10-15min to obtain a microencapsulated timicosin premix.

10. The process for the preparation of microencapsulated tilmicosin premix as claimed in claim 9, wherein, The inlet air temperature of spray drying in step 3 is 180-220℃, and the outlet air temperature is 80-100℃.

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