A medicine for treating mycoplasma hyopneumoniae and a preparation method thereof

Abstract

The present application provides a kind of drug for treating mycoplasma hyopneumoniae, the drug combination of the present application can inhibit the replication of mycoplasma hyopneumoniae and control the complications and sequelae caused by infection, for the treatment and prevention of mycoplasma hyopneumoniae, the present application starts from substance metabolism, by correcting the disorder of substance metabolism, thereby well control the harm caused by mycoplasma hyopneumoniae, well control the occurrence of mycoplasma pneumonia.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, and in particular to a drug for treating Mycoplasma pneumoniae in pigs and its preparation method. Background Technology

[0002] Mycoplasma pneumonia of swine (MPS) is a chronic respiratory disease in pigs caused by Mycoplasma hyopneumoniae (Mhp). Although it is not highly resistant to external environmental and physicochemical factors, it can persist in the pig's body for a long time, causing persistent infection. According to serological testing statistics from large-scale pig farms in my country, the positive rate is 30%-50%. Infected pigs experience slow growth and development, with a growth rate reduction of about 15% and feed utilization rate reduction of 20%, resulting in significant waste of feed and labor. After Mhp challenge or infection, clinical manifestations include coughing, wheezing, and typical muscular lesions and interstitial pneumonia in the lungs, along with loss of cilia in the bronchial tubes.

[0003] Although vaccines, drugs, and preventative measures have been developed, they still cannot effectively control the occurrence of this disease. It is necessary to analyze the pathogenic mechanism of Mycoplasma pneumoniae in order to find suitable targets for better prevention and control of porcine mycoplasma pneumonia. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides a drug for treating Mycoplasma pneumoniae in pigs and a method for its preparation. This drug can inhibit the replication of Mycoplasma pneumoniae and control complications and sequelae caused by infection, and is used for the treatment and prevention of Mycoplasma pneumoniae in pigs.

[0005] To achieve the above objectives, the present invention provides the following technical solution:

[0006] A drug for treating Mycoplasma hyopneumoniae in pigs, by weight, comprises the following components per 1 mL solution:

[0007]

[0008]

[0009] As a further aspect of the present invention, adjuvant 201 is a biphase adjuvant used to fuse the aqueous phase and the oil phase. As a further aspect of the present invention, based on weight, 1 ml of solution comprises the following components:

[0010] As a further aspect of the present invention, the solution, calculated by weight per 1 ml, comprises the following components:

[0011] As a further aspect of the present invention, the solution, calculated by weight per 1 ml, comprises the following components:

[0012] As a further embodiment of the present invention, the 25HC is used to inhibit cholesterol synthesis by downregulating the expression of cholesterol synthesis-related genes by inhibiting the activation of transcription factor SREBP; and to promote the efflux and esterification of intracellular cholesterol by activating LXR, thereby promoting the efflux of intracellular cholesterol and bile synthesis.

[0013] As a further aspect of the present invention, the ursodeoxycholic acid is used to regulate the endoplasmic reticulum's stress response capacity, including both reducing the activation of endoplasmic reticulum stress-coupled inflammatory and apoptotic signals and increasing the effective transmission of XBP1 pathway-insulin metabolism signals.

[0014] In this invention, the drug for treating Mycoplasma pneumoniae in pigs is emulsified to form an emulsion for intramuscular injection. This drug can inhibit the replication of Mycoplasma pneumoniae and control complications and sequelae caused by infection, and is used for the treatment and prevention of Mycoplasma pneumoniae in pigs.

[0015] This invention also provides a method for preparing a drug for treating Mycoplasma pneumoniae in pigs, comprising the following steps:

[0016] 25HC was dissolved in phosphate buffer;

[0017] Lovastatin and ursodeoxycholic acid were slowly added to adjuvant 201 and emulsified by stirring.

[0018] Mix the dissolved 25HC with the emulsion until homogeneous;

[0019] Adjust the volume using phosphate buffer.

[0020] Among them, adjuvant 201 is a biphasic adjuvant that can effectively blend the aqueous and oil phases. Lovastatin and ursodeoxycholic acid are insoluble in water but soluble in oils. In the preparation process, 25HC is dissolved in phosphate buffer, and then lovastatin and ursodeoxycholic acid are slowly added to adjuvant 201, stirred and emulsified at 2000 rpm to form a homogeneous liquid, which is then mixed with 25HC and finally brought to a final volume with phosphate buffer.

[0021] The present invention has the following beneficial effects:

[0022] The drug combination of the present invention can inhibit the replication of Mycoplasma pneumoniae and control the complications and sequelae caused by infection, and can be used for the treatment and prevention of Mycoplasma pneumoniae in pigs.

[0023] Existing control strategies focus on inhibiting mycoplasma replication, but these strategies are difficult to prevent mycoplasma infection. This invention addresses the issue by focusing on metabolism and correcting disordered metabolism, thereby effectively controlling the harm caused by Mycoplasma pneumoniae in pigs and significantly reducing the incidence of mycoplasma pneumonia. Detailed Implementation

[0024] The present invention will be further described below with reference to embodiments and relevant knowledge. Obviously, the described applications are only some embodiments of the present invention, and not all embodiments.

[0025] This invention provides a drug combination for treating Mycoplasma pneumoniae in pigs. This drug can inhibit the replication of Mycoplasma pneumoniae and control complications and sequelae caused by infection, and is used for the treatment and prevention of Mycoplasma pneumoniae in pigs.

[0026] This invention addresses the issue of mycoplasma pneumoniae in porcines by correcting metabolic disorders, effectively controlling the disease and incidence of mycoplasma pneumonia. Specifically, in the first 14 days after Mph infection, the disease primarily disrupts pathways related to cholesterol metabolism, apoptosis signaling, inflammation signaling, and protein modification. By day 28, these disrupted pathways are concentrated in cholesterol metabolism, inflammation, apoptosis, signal transduction, and functional impairment. Cholesterol metabolism and inflammation play major roles in Mph infection. By regulating cholesterol levels and restoring them to normal, porcine mycoplasma pneumonia can be effectively controlled.

[0027] In the mevalonate pathway, HMGCR, as the rate-limiting enzyme in cholesterol biosynthesis, is a glycoprotein located at the endogenous endothelial cell line (ER). Statins, specifically HMG-CoA reductase inhibitors, not only potently lower total cholesterol (TC) and low-density lipoprotein (LDL), but also work by competitively inhibiting HMG-CoA reductase, the rate-limiting enzyme in endogenous cholesterol synthesis, thereby blocking the intracellular mevalonate metabolic pathway and reducing intracellular cholesterol synthesis. In the negative feedback mechanism of cholesterol synthesis, oxycholesterol, especially 25-hydroxycholesterol (25HC), exhibits a stronger negative feedback effect.

[0028] In this invention, the main functions of 25HC are: 1) inhibiting de novo cholesterol synthesis: by blocking the activation of the transcription factor SREBP, downregulating the expression of genes related to de novo cholesterol synthesis; and 2) promoting intracellular cholesterol efflux and esterification: by activating LXR, thereby promoting intracellular cholesterol efflux and bile synthesis. Mycoplasma hyopneumoniae infection in swine pneumonia causes a significant increase in intracellular cholesterol and cholesterol in blood lipids. This cholesterol is transported to the liver via reverse transport, greatly increasing the liver's cholesterol concentration. In cholesterol metabolism, synthesis and excretion are in a strictly regulated dynamic balance. If cholesterol in the liver cannot be transferred in a timely manner, metabolic abnormalities and inflammation will occur.

[0029] Ursodeoxycholic acid (UDCA) is a natural molecular chaperone that helps endoplasmic reticulum (ER) proteins fold and can effectively regulate ER stress response, including reducing ER stress-coupled inflammatory and apoptotic signaling activation and increasing the effective transmission of XBP1 pathway-insulin metabolic signals. It has protective effects on hepatocellular carcinoma cells, promotes bile secretion, and has anti-inflammatory, antioxidant, anti-apoptotic, and immunomodulatory effects. It is a choleretic hydrophilic bile acid. UDCA can increase the conversion of cholesterol into bile acids, effectively alleviating cholesterol accumulation in the liver.

[0030] This invention synthesizes, eliminates, and rapidly transforms cholesterol metabolism imbalances at the source. It can inhibit the replication of Mycoplasma pneumoniae and control complications and sequelae caused by infection, making it suitable for the treatment and prevention of Mycoplasma pneumoniae in pigs.

[0031] Example 1

[0032] A drug for treating Mycoplasma pneumoniae in pigs. By weight, 1 ml of solution comprises the following components:

[0033]

[0034] The preparation method is as follows: 25HC is dissolved in phosphate buffer; lovastatin and ursodeoxycholic acid are slowly added to adjuvant 201 and stirred to emulsify; the dissolved 25HC is mixed evenly with the emulsion; and the volume is adjusted with phosphate buffer to obtain the drug for treating porcine mycoplasma pneumoniae.

[0035] In a severely infected pig farm, 10 litters (108 piglets in total) were randomly selected and injected with the drug at 2 ml / piglet. Another 10 litters were selected as a control group. By the end of the nursery period, the proportion of coughing and wheezing in the injected group was less than 5%. The results of the control group are shown in Table 1.

[0036] Table 1. Statistical Table of Treatment Results

[0037] Treatment group 108 2 1.85％(2 / 108) control group 110 67 60.9％(67 / 110)

[0038] Referring to Table 1, the proportion of cough and wheezing in the treatment group using the drug combination of the present invention was 1.85%, which was significantly lower than 60.9% in the control group.

[0039] Example 2

[0040] A drug for treating Mycoplasma pneumoniae in pigs. By weight, 1 ml of solution comprises the following components:

[0041]

[0042] Ten piglets in the late nursery stage were randomly divided into two groups. One group received 2 ml of the drug per piglet for 7 consecutive days. The other group served as a control and was not injected. The pigs were then observed for 15 consecutive days. After the experiment, the pigs were euthanized, and their lungs were scored. The lung lesions in the injected group were significantly less severe than those in the control group. The results are shown in Table 2.

[0043] Table 2 Lung Scoring Table

[0044] The number of heads corresponding to the score in the medication group 2 2 1 0 0 0 0 Control group score corresponding to number of heads 0 0 0 0 1 1 3

[0045] Example 3

[0046] A drug for treating Mycoplasma pneumoniae in pigs. By weight, 1 ml of solution comprises the following components:

[0047]

[0048] One hundred piglets in the late nursery stage were randomly divided into two groups. One group was injected with the drug at a dose of 2 ml per piglet for three days each month. The other group served as a control and was not injected. Observations were conducted continuously until slaughter. Daily weight gain was calculated, and the results are shown in Table 3.

[0049] Table 3: Daily Weight Gain Statistics

[0050] Treatment group 50 512 control group 50 426

[0051] Table 4. Correspondence between Lung Scoring Criteria and Daily Weight Loss

[0052]

[0053] As shown in Table 3, the daily weight gain of the treatment group after using the drug combination of the present invention was significantly higher than that of the control group.

[0054] The technical principles of the present invention have been described above with reference to specific embodiments, which are merely preferred embodiments of the present invention. The scope of protection of the present invention is not limited to the above embodiments; all technical solutions falling within the scope of the present invention's concept are within its protection scope. Those skilled in the art can conceive of other specific embodiments of the present invention without creative effort, and these embodiments will all fall within the protection scope of the present invention.

Claims

1. A drug for treating Mycoplasma pneumoniae in pigs, characterized in that, The solution, by weight, comprises the following components per 1 mL: 25HC 0.5 mg–3 mg; lovastatin 10 mg–40 mg; ursodeoxycholic acid 100 mg–300 mg; 201 adjuvant 0.1 mL–0.2 mL; and phosphate buffer to a final volume of 1 mL. The 201 adjuvant is a biphasic adjuvant used to fuse the aqueous and oil phases.

2. The drug for treating Mycoplasma pneumoniae in pigs as described in claim 1, characterized in that, The solution, by weight, comprises the following components per 1 ml: 25HC 0.5 mg; lovastatin 10 mg; ursodeoxycholic acid 200 mg; 201 adjuvant 0.1 mL; and phosphate buffer to a final volume of 1 mL.

3. The drug for treating Mycoplasma pneumoniae in pigs as described in claim 1, characterized in that, The solution, by weight, comprises the following components per 1 ml: 25HC 2 mg; lovastatin 40 mg; ursodeoxycholic acid 100 mg; and 201 adjuvant 0.2 mL phosphate buffer, brought to a final volume of 1 mL.

4. The drug for treating Mycoplasma pneumoniae in pigs as described in claim 1, characterized in that, The solution, by weight, comprises the following components per 1 ml: 25HC 3 mg; lovastatin 20 mg; ursodeoxycholic acid 300 mg; 201 adjuvant 0.15 mL; and phosphate buffer to a final volume of 1 mL.

5. A method for preparing a drug for treating Mycoplasma hyopneumoniae as described in claim 1, characterized in that, Includes the following steps: 25HC was dissolved in phosphate buffer; Lovastatin and ursodeoxycholic acid were slowly added to adjuvant 201 and emulsified by stirring. Mix the dissolved 25HC with the emulsion until homogeneous; Adjust the volume using phosphate buffer.

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