Composite pharmaceutical composition for preventing and treating avian salmonella infection and application thereof

Abstract

The invention belongs to the field of veterinary drugs, and particularly relates to a composite pharmaceutical composition for preventing and treating avian salmonella infection and application of the composite pharmaceutical composition. The composition comprises the following components in parts by weight: florfenicol, coptis chinensis and schisandra chinensis extract, vitamin C and prebiotics. Florfenicol and specific traditional Chinese medicines are combined and matched with sufficient vitamin C and prebiotics to form an antibacterial-protection-repair three-in-one synergistic system. On the premise of remarkably reducing the dosage of florfenicol, the compound can achieve a better clinical curative effect, relieve toxic and side effects and promote rapid rehabilitation of infected poultry, has obvious comprehensive advantages and is suitable for preparing a medicine for preventing and treating avian salmonellosis.

Description

Technical Field

[0001] This invention belongs to the field of veterinary drugs, specifically relating to a compound drug composition for preventing and treating Salmonella infection in poultry and its application. Background Technology

[0002] Salmonella is an important zoonotic enteric pathogen that is ubiquitous in nature. It can cause diseases such as pullorum disease in chicks and fowl typhoid, leading to stunted growth and increased mortality in poultry, posing a significant threat to the poultry industry. As a major cause of foodborne illness globally, Salmonella infection in humans often results in gastrointestinal discomfort and can even trigger poisoning or shock. In other words, Salmonella poses a serious threat to both poultry health and food safety.

[0003] Currently, florfenicol is a commonly used antibiotic for the prevention and treatment of Salmonella infection in poultry. However, long-term and irrational use of single antibiotics has led to increasingly prominent problems such as increased drug resistance, drug residues, and toxic side effects.

[0004] Therefore, it is of great significance to develop a new compound that can effectively overcome drug resistance, reduce antibiotic usage, ensure safety and low residues, and comprehensively enhance the disease resistance of poultry. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a compound drug composition for the prevention and treatment of Salmonella infection in poultry, which has good component synergy, significant efficacy, high safety, and more comprehensive benefits. This composition achieves synergistic integration of antibacterial, toxicity-reducing, gut-protecting, and immune-enhancing effects through the innovative combination of florfenicol, specific traditional Chinese medicine extracts, and key functional excipients vitamin C and prebiotics.

[0006] Another object of the present invention is to provide a method for preparing the above-mentioned compound pharmaceutical composition and its application.

[0007] Specifically, the present invention is achieved through the following technical solutions:

[0008] In a first aspect, the present invention provides a compound pharmaceutical composition for preventing and treating Salmonella infection in birds, characterized in that it comprises, by weight, the following active ingredients:

[0009] Florfenicol 10-30 parts;

[0010] 30-50 parts of Chinese herbal extract;

[0011] Vitamin C 10-30 servings;

[0012] 30-70 servings of prebiotics.

[0013] Preferably, the herbal extract is prepared by extracting dried Coptis chinensis and Schisandra chinensis, wherein the weight ratio of Coptis chinensis to Schisandra chinensis is 1:1 to 3:1. More preferably, the weight ratio of Coptis chinensis to Schisandra chinensis is 2:1.

[0014] Preferably, the herbal extract is an aqueous or alcoholic extract of Coptis chinensis and Schisandra chinensis.

[0015] Preferably, the vitamin C is coated vitamin C or vitamin C phosphate.

[0016] Preferably, the prebiotic is selected from one or more of fructooligosaccharides, galactooligosaccharides, mannan oligosaccharides, and inulin.

[0017] Preferably, the composite pharmaceutical composition may further include a pharmaceutically acceptable carrier and / or excipients. More preferably, the carrier includes starch, glucose, etc.

[0018] Secondly, the present invention provides a method for preparing the above-mentioned compound pharmaceutical composition, the method comprising: placing a specified amount of florfenicol raw material, dried powder of traditional Chinese medicine extract, vitamin C and prebiotics, optionally with a pharmaceutically or feed-acceptable carrier, in a mixing device, and mixing thoroughly until homogeneous to prepare a premix or granules.

[0019] Thirdly, the present invention provides the use of the above-mentioned compound pharmaceutical composition in the preparation of a medicament or feed additive for the prevention and / or treatment of Salmonella infection in poultry.

[0020] Preferably, the poultry includes chickens, ducks, geese, turkeys, etc. More preferably, the poultry is chicken.

[0021] Preferably, the pharmaceutical composition or feed additive can be administered to poultry via drinking water, mixing with feed, or spraying. More preferably, the pharmaceutical composition or feed additive is administered to poultry via mixing with feed. When used for treatment, the daily dose of florfenicol in the pharmaceutical composition can be reduced to 10 mg / kg body weight, lower than the conventional dose of its single-component formulation (20-30 mg / kg body weight).

[0022] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here.

[0023] Compared with the prior art, the present invention has the following advantages:

[0024] 1. Synergistic effect of "antibacterial-protection-repair":

[0025] This composition creatively combines the antibacterial ingredient florfenicol with a specific ratio of Coptis chinensis-Schisandra chinensis extract. Coptis chinensis, whose main active components are alkaloids such as berberine, possesses broad-spectrum and strong antibacterial and anti-inflammatory effects, and has a direct inhibitory effect on Salmonella. Schisandra chinensis, rich in lignans, exhibits significant antioxidant, anti-inflammatory, and immune-enhancing effects, and can protect the liver and reduce stress damage caused by infection and drugs. Coptis chinensis primarily "attacks" (antibacterial and anti-inflammatory), while Schisandra chinensis primarily "defends" (liver protection and immunity). While powerfully eliminating pathogens, it effectively regulates the immune function of poultry, promoting recovery and embodying the traditional Chinese medicine principle of "strengthening the body's resistance and eliminating pathogens."

[0026] As an antioxidant, vitamin C can effectively eliminate free radicals generated during infection and drug metabolism, relieve oxidative stress, enhance poultry immune function, and assist in the body's recovery.

[0027] Prebiotics selectively promote the proliferation of beneficial bacteria in the gut, maintain the balance of the gut microbiota, and help restore gut health without antagonizing antibiotics.

[0028] The components in the composition work synergistically through multiple mechanisms, forming a complete action chain from "clearing pathogens" to "protecting the body" and then to "repairing the body", which can achieve a significant synergistic effect.

[0029] 2. Significantly Reduced Antibiotic Dosage and Toxicity: The components in the composition have complementary mechanisms of action, significantly reducing over-reliance on and use of antibiotics in aquaculture. A specific ratio (especially 2:1) of Coptis chinensis-Schisandra chinensis extract, used in combination with florfenicol, exhibits a significant synergistic antibacterial effect against avian Salmonella. This allows for a reduction of florfenicol dosage by more than 50% while achieving the same or even better therapeutic effects, fundamentally reducing antibiotic exposure and residue risks. Furthermore, the hepatoprotective and antioxidant effects of Schisandra chinensis and Vitamin C directly counteract the potential hepatic metabolic burden and oxidative damage caused by the drugs, thereby reducing antibiotic toxicity and improving medication safety.

[0030] 3. Enhanced Overall Production Performance: This composition not only effectively controls diseases, but also improves poultry appetite, promotes growth, and increases feed conversion rate due to the anti-stress effect of vitamin C. Prebiotics selectively promote the proliferation of beneficial intestinal bacteria and maintain microecological balance without antagonizing antibiotics. The anti-inflammatory and immunomodulatory functions of the traditional Chinese medicine components help control systemic inflammation caused by infection, promote poultry recovery, and improve survival rate and production performance.

[0031] 4. Excellent stability: The composition does not contain live bacteria or special mineral components, avoiding antagonism with antibiotics and complex physical compatibility issues. It has relaxed requirements for processing and storage conditions, and the product quality is stable, making it suitable for long-term storage. Detailed Implementation

[0032] The present invention will be further described below with reference to specific embodiments. It should be understood that the specific embodiments described herein are for illustrative purposes only and are not intended to limit the scope of the invention.

[0033] Where specific techniques or conditions are not specified in the examples, they shall be performed in accordance with the techniques or conditions described in the literature in this field, or in accordance with the product instructions. Reagents or instruments whose manufacturers are not specified are all conventional products that can be purchased through legitimate channels.

[0034] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods. Unless otherwise specified, the experimental materials used in the following embodiments are commercially available products.

[0035] Florfenicol was purchased from Zhejiang Kangmu Animal Health Co., Ltd., with a content of ≥98%.

[0036] Unless otherwise stated, all percentages and parts in this invention refer to weight percentages and weight parts.

[0037] Example 1

[0038] Take 200g of dried Coptis chinensis and 100g of Schisandra chinensis, and grind them into coarse powder. Extract twice with 8 times the volume of 60% ethanol, 1.5 hours each time. Combine the extracts, filter, concentrate under reduced pressure to a paste, dry and grind to obtain 75g of Coptis chinensis-Schisandra chinensis compound extract for later use.

[0039] Example 2

[0040] Compared with Example 1, the difference lies in the amount of Coptis chinensis and Schisandra chinensis (150g), while the preparation process is the same as in Example 1.

[0041] Example 3

[0042] Compared with Example 1, the difference lies in the amount of Coptis chinensis 225g and Schisandra chinensis 75g, while the preparation process is the same as in Example 1.

[0043] Example 4

[0044] Compared with Example 1, the difference lies in the amount of Coptis chinensis 100g and Schisandra chinensis 200g, while the preparation process is the same as in Example 1.

[0045] Example 5

[0046] Compared with Example 1, the difference lies in the amount of Coptis chinensis 240g and Schisandra chinensis 60g, while the preparation process is the same as in Example 1.

[0047] Example 6

[0048] Weigh each component according to the following weight ratio:

[0049] • 20 portions of florfenicol

[0050] • Coptis chinensis-Schisandra chinensis compound extract dry powder (prepared in Example 1) 35 parts

[0051] • Coated Vitamin C (50% content) 40 servings (equivalent to 20 servings of pure Vitamin C)

[0052] • 50 parts of mannan oligosaccharide

[0053] •875 parts starch

[0054] Mix all the above components thoroughly and evenly, and pass through a 100-mesh sieve to obtain a powdered composite drug composition.

[0055] Example 7

[0056] Compared with Example 6, the only difference is that the Coptis-Schisandra compound extract prepared in Example 1 is replaced with the Coptis-Schisandra compound extract prepared in Example 2, while other conditions and parameters are the same as in Example 6, and a powdered compound pharmaceutical composition is obtained.

[0057] Example 8

[0058] Compared with Example 6, the only difference is that the Coptis-Schisandra compound extract prepared in Example 1 is replaced with the Coptis-Schisandra compound extract prepared in Example 3, while other conditions and parameters are the same as in Example 6, and a powdered compound pharmaceutical composition is obtained.

[0059] Example 9

[0060] Compared with Example 6, the only difference is that the Coptis-Schisandra compound extract prepared in Example 1 is replaced with the Coptis-Schisandra compound extract prepared in Example 4, while other conditions and parameters are the same as in Example 6, and a powdered compound pharmaceutical composition is obtained.

[0061] Example 10

[0062] Compared with Example 6, the only difference is that the Coptis-Schisandra compound extract prepared in Example 1 is replaced with the Coptis-Schisandra compound extract prepared in Example 5, while other conditions and parameters are the same as in Example 6, and a powdered compound pharmaceutical composition is obtained.

[0063] Comparative Example 1

[0064] Weigh each component according to the following weight ratios. The preparation process is exactly the same as in Example 6.

[0065] • 20 portions of florfenicol

[0066] • Coated Vitamin C (50% content) 40 servings (equivalent to 20 servings of pure Vitamin C)

[0067] • 50 parts of mannan oligosaccharide

[0068] • 910 parts starch

[0069] Comparative Example 2

[0070] Weigh each component according to the following weight ratios. The preparation process is exactly the same as in Example 6.

[0071] • 55 portions of florfenicol

[0072] • Coated Vitamin C (50% content) 40 servings (equivalent to 20 servings of pure Vitamin C)

[0073] • 50 parts of mannan oligosaccharide

[0074] •875 parts starch

[0075] Comparative Example 3

[0076] The florfenicol (55 parts) and starch (945 parts) were mixed evenly to obtain the product.

[0077] Comparative Example 4

[0078] Weigh each component according to the following weight ratios. The preparation process is exactly the same as in Example 6.

[0079] • Coptis chinensis-Schisandra chinensis compound extract dry powder (prepared in Example 1) 35 parts

[0080] • Coated Vitamin C (50% content) 40 servings (equivalent to 20 servings of pure Vitamin C)

[0081] • 50 parts of mannan oligosaccharide

[0082] •895 parts starch

[0083] Trial Example 1: Comparative Trial of Therapeutic Effects

[0084] 1.1 Strains used for challenge: *Salmonella Pullorum*, BNCC 124693, purchased from Beijing Beina Chuanglian Biotechnology Research Institute. Fresh cultures of *Salmonella* were inoculated into tryptic soy broth and incubated at 30-35°C with shaking for 24 hours to adjust the bacterial concentration to 1.0 × 10⁻⁶. 8 CFU / mL, store at 37℃ for later use.

[0085] 1.2 Experimental animals: One-day-old Liangfenghua broiler chickens were purchased from Yongdeng Branch of Baiyin Tongren Poultry Breeding Co., Ltd., and were raised in pollution-free cages with a room temperature of 20 to 24℃ and a relative humidity of 50±10%. The feed was complete broiler feed (medicated compound feed) purchased from Lanzhou Yangdongli Feed Co., Ltd. Feeding was provided three times a day, and water was available freely.

[0086] 1.3 Experimental Methods: At 14 days of age, 220 healthy chicks in good condition were randomly divided into 11 groups of approximately 20 chicks each. After grouping, except for the healthy control group, all other groups received an intraperitoneal injection of 0.6 mL of Salmonella suspension. Treatment groups were administered medication after the onset of clinical symptoms. Specifically, the drug compositions prepared in Examples 6 to 10 and Comparative Examples 1 to 4 were added to the basal diet at a ratio of 25 g of drug composition per 10 kg of chicken feed, and fed continuously for 7 days. The healthy control group and the infected control group received no medication. The healthy control group was fed the basal diet and kept in isolation. During the treatment period, the onset and recovery of the disease in each group were closely monitored. The mortality rate, effectiveness rate, and cure rate of each group were observed and recorded. Necropsy was performed on the dead chickens, and the liver or lungs were aseptically collected for bacterial isolation and identification.

[0087] 1.4 Efficacy assessment and observation indicators

[0088] Mortality: Chickens exhibiting typical symptoms of pullorum disease and dying during the experiment, with necropsy revealing typical pathological features, and Salmonella pullorum isolated and cultured from the liver, spleen, and heart, were determined to have died from infection with this bacterium. The mortality rate for each group was calculated based on the number of dead chickens.

[0089] Cure: After administration, the chickens' mental state and appetite returned to normal, the soft crop symptoms disappeared, there was no more pasty feces, and typical symptoms such as downy hairs around the anus and inflammation around the anus disappeared; suspected colonies isolated from fecal samples were not isolated from typical Salmonella colonies by xylose lysine deoxycholate identification culture, and were judged as cured.

[0090] Effective: After administration, the above-mentioned clinical symptoms of chickens improved significantly, diarrhea symptoms were reduced, and mental state, appetite, and respiration gradually returned to normal, which was judged as effective.

[0091] 1.5 Test Results

[0092] The experimental results are detailed in Table 1.

[0093] Table 1. Efficacy results of each treatment group and control group against chicken salmonellosis (n=20)

[0094] Group Number of deaths (animals) mortality rate(%) Effectiveness (%) Cure rate (%) Average daily weight gain (g / animal) healthy control group - - - - 17.8 Infection control group 12 60 - - 10.3 Treatment Group 1 (Example 6) 0 0 100 100 22.7 Treatment Group 2 (Example 7) 0 0 100 100 19.9 Treatment Group 3 (Example 8) 0 0 100 100 19.2 Treatment Group 4 (Example 9) 1 5 95 95 18.2 Treatment group 5 (Example 10) 1 5 95 95 17.6 Control Group 1 (Comparative Example 1) 4 20 80 80 16.4 Control Group 2 (Comparative Example 2) 2 10 90 85 16.8 Control Group 3 (Comparative Example 3) 3 15 85 80 15.2 Control Group 4 (Comparative Example 4) 2 10 90 90 17.0

[0095] Results analysis:

[0096] 1. Mortality Rate: Compared with the infected control group, which had a mortality rate of 60%, the mortality rates of chickens in treatment groups 1-5 and control groups 1-4 were significantly reduced, ranging from only 0% to 20%. In particular, no chickens died in treatment groups 1-3, with a mortality rate of 0%. The mortality rates in treatment groups 3 and 4 (5%) were significantly lower than those in control groups 1-4 (10% to 20%). This strongly demonstrates that the compound pharmaceutical composition of the present invention can greatly improve the survival rate of diseased poultry.

[0097] 2. In terms of production performance: The average daily weight gain of chickens in treatment groups 1 to 3 was the most significant, and was significantly higher than that of the healthy control group and the control group. This indicates that the drug composition provided by this invention not only has a good therapeutic effect on avian salmonellosis, but also has few toxic side effects, while simultaneously improving relative weight gain and production performance. The traditional Chinese medicine components (especially the hepatoprotective and immunomodulatory effects of Schisandra chinensis) and vitamin C played a key role in promoting the recovery and growth of poultry after infection.

[0098] 3. Regarding the cure rate: After 7 days of medication, the mental state and appetite of the chicks in treatment groups 1 to 3 and the surviving chicks in treatment groups 4 and 5 basically returned to normal; after 7 days of medication, the chicks in treatment groups 1 to 3 and the surviving chicks in treatment groups 4 and 5 no longer excreted pasty grayish-white watery feces, and the fecal samples were isolated and cultured on a differential culture medium, and no typical Salmonella colonies were detected, which can be judged as a cure.

[0099] 4. Overall Conclusion: Each treatment group was able to rapidly alleviate the clinical symptoms of diarrhea, with quick results. Through comparison, it was confirmed that the combination of traditional Chinese medicine extracts (extracts of Coptis chinensis and Schisandra chinensis, especially extracts of Coptis chinensis and Schisandra chinensis in a specific ratio) with florfenicol is an essential technical feature of this invention. It makes outstanding contributions to improving the overall prevention and treatment effect, reducing mortality and promoting growth, and its effect is far superior to the schemes that use only antibiotics and only traditional Chinese medicine combinations.

[0100] Test Example 2: Florfenicol Residue Test

[0101] On the 7th day after drug withdrawal in the above experiment, pectoral muscle and liver samples were collected from chickens in each group. Florfenicol in the pectoral muscle and liver samples was determined by SPE-UPLC-MS / MS method according to GB 31658.5-2021 standard. The results are shown in Table 2.

[0102] Table 2. Florfenicol concentration in chicken liver and muscle tissue (μg / kg, n=20)

[0103] Group liver muscle Treatment Group 1 (Example 6) 671.73±15.43 26.74±1.78 Treatment Group 2 (Example 7) 665.96±26.15 36.45±2.65 Treatment Group 3 (Example 8) 704.89±19.67 32.42±1.89 Treatment Group 4 (Example 9) 606.12±13.47 13.43±1.45 Treatment group 5 (Example 10) 705.43±23.78 39.56±3.93 Control Group 1 (Comparative Example 1) 1678.47±106.96 59.79±5.23 Control Group 2 (Comparative Example 2) 2765.27±148.39 98.72±6.85 Control Group 3 (Comparative Example 3) 3864.57±187.43 258.77±19.83 Control Group 4 (Comparative Example 4) - -

[0104] The results showed that the florfenicol content in the liver and muscle tissue of chickens in treatment groups 1 to 5 was lower than the relevant national limits (Ministry of Agriculture and Rural Affairs Announcement No. 235, "Maximum Residue Limits for Veterinary Drugs in Animal-Derived Foods," with a limit of 100 μg / kg for florfenicol in muscle and 2500 μg / kg for florfenicol in liver), meeting the hygiene and safety requirements for animal-derived foods. However, the florfenicol content in the liver and muscle tissue of chickens in control groups 1 to 3 was significantly higher than that in treatment groups 1 to 5, indicating that the compound drug composition of the present invention effectively reduced the accumulation of florfenicol in animals.

[0105] The above examples and experimental data fully demonstrate that the compound pharmaceutical composition provided by the present invention, through the scientific combination of florfenicol, a specific ratio of Coptis chinensis-Schisandra chinensis extract, vitamin C and prebiotics, produces a comprehensive effect of synergistic enhancement, dosage reduction and toxicity reduction, and protection of the body. Its technical effect is significantly better than that of florfenicol alone.

[0106] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A compound pharmaceutical composition for preventing and treating Salmonella infection in poultry, characterized in that, Its active ingredients, by weight, consist of the following components: Florfenicol 10-30 parts; 30-50 parts of Chinese herbal extract; Vitamin C 10-30 servings; 30-70 servings of prebiotics.

2. The compound pharmaceutical composition according to claim 1, characterized in that, The herbal extract is prepared by extracting dried Coptis chinensis and Schisandra chinensis in a weight ratio of 1:1 to 3:

1.

3. The compound pharmaceutical composition according to claim 2, characterized in that, The weight ratio of Coptis chinensis to Schisandra chinensis is 2:

1.

4. The compound pharmaceutical composition according to claim 1, characterized in that, The vitamin C mentioned is encapsulated vitamin C or magnesium vitamin C phosphate.

5. The compound pharmaceutical composition according to claim 1, characterized in that, The prebiotics are selected from one or more of fructooligosaccharides, galactooligosaccharides, mannan oligosaccharides, and inulin.

6. The compound pharmaceutical composition according to claim 1, characterized in that, The composite pharmaceutical composition also includes a pharmaceutically acceptable carrier.

7. A method for preparing the compound pharmaceutical composition according to any one of claims 1-6, characterized in that, include: Mix each active ingredient with the carrier until homogeneous.

8. Use of the compound pharmaceutical composition according to any one of claims 1-6 in the preparation of a medicament or feed additive for the prevention or treatment of Salmonella infection in poultry.

9. The application according to claim 8, characterized in that, The drugs or feed additives are administered to poultry via drinking water, mixing with feed, or spraying.

10. The application according to claim 9, characterized in that, When used for treatment, the daily dose of florfenicol in the compound pharmaceutical composition is 10 mg / kg body weight.