A pharmaceutical composition for preventing and treating zearalenone poisoning in pigs

Abstract

This application belongs to the field of pharmaceutical technology, and specifically relates to a pharmaceutical composition for preventing and treating porcine zearalenone poisoning. The pharmaceutical composition comprises the following components in parts by weight: Morinda officinalis 1 - 15 parts, Acacia vine 1 - 15 parts, Bupleurum chinense 1 - 15 parts, and Rehmannia glutinosa 1 - 15 parts. The research results of the present invention show that it can relieve the phenomena of vulva swelling and uterine enlargement in pigs poisoned by zearalenone, accelerate the health recovery of pigs, and reduce the economic losses caused by zearalenone toxin poisoning.

Description

Technical Field

[0001] This application belongs to the field of pharmaceutical technology, and specifically relates to a pharmaceutical composition for preventing and treating porcine zearalenone poisoning. Background Art

[0002] Zearalenone (ZEA), 6-(10-hydroxy-6-oxo-undecenyl)-β-resorcylic acid lactone, is a reproductive system toxin with strong teratogenic effects. It can cause a decline in the growth rate, immunosuppression, and reproductive disorders in various livestock and poultry, thus posing a serious threat to the livestock industry. Among them, pigs are one of the most common and severely affected animals by ZEA. Due to its special metabolic mechanism in pigs, its sensitivity is more than a hundred times higher than that of other animals. It mainly causes reproductive dysfunction in sows, leading to infertility, estrus disorders, reduced litter size, or fetal malformations in sows. Currently, the main ZEA detoxification technologies are adsorption and biodegradation methods. The former still has significant problems in terms of adsorption range, practicability, effectiveness, and safety. The latter is the development trend of ZEA and other mycotoxin detoxification, but its degradation mechanism research is still not deep enough, and there are problems such as unstable degradation ability and degradation of the strains. The Chinese herbal medicine mycotoxin antidote aims to improve the liver's own detoxification and the kidney's detoxification function, neutralize the mycotoxins in the body, antagonize the mycotoxins in the body, and achieve the purpose of detoxification by regulating the body's state. Using anti-estrogen Chinese herbal medicine to prevent and treat ZEA-poisoned pigs is a relatively feasible implementation plan. Summary of the Invention

[0003] Based on a scientific screening method, the formula screened by the present invention is safe, effective, has a good therapeutic effect on the poisoning symptoms caused by ZEA toxin, can enhance the animal's own detoxification ability, is simple to prepare, has a low cost, and has good prospects.

[0004] The specific technical solution is as follows:

[0005] A pharmaceutical composition for preventing and treating porcine zearalenone poisoning, comprising the following components in parts by weight: Morinda officinalis 1 - 15 parts, Abrus cantoniensis 1 - 15 parts, Bupleurum chinense 1 - 15 parts, Rehmannia glutinosa 1 - 15 parts.

[0006] The pharmaceutical composition of the present invention comprises the following components in parts by weight: Morinda officinalis 3 - 10 parts, Abrus cantoniensis 3 - 10 parts, Bupleurum chinense 2 - 10 parts, Rehmannia glutinosa 3 - 10 parts.

[0007] The pharmaceutical composition described in the present invention comprises the following components in parts by weight: Morinda officinalis 3 parts, Acacia vine 10 parts, Bupleurum chinense 2 parts, Rehmannia glutinosa 10 parts; or, Morinda officinalis 3 parts, Acacia vine 3 parts, Bupleurum chinense 3 parts, Rehmannia glutinosa 3 parts; or, Morinda officinalis 10 parts, Acacia vine 10 parts, Bupleurum chinense 5 parts, Rehmannia glutinosa 5 parts; or, Morinda officinalis 5 parts, Acacia vine 5 parts, Bupleurum chinense 10 parts, Rehmannia glutinosa 10 parts; or, Morinda officinalis 5 parts, Acacia vine 10 parts, Bupleurum chinense 10 parts, Rehmannia glutinosa 5 parts.

[0008] The present invention provides a method for preparing the pharmaceutical composition, which is to pulverize the traditional Chinese medicine raw materials with a pharmaceutical pulverizer and then premix them evenly.

[0009] The pharmaceutical composition described in the present invention is used for preventing and treating zearalenone poisoning in pigs.

[0010] Specifically, the present invention provides the following examples:

[0011] Example 1: Morinda officinalis 3 g, Acacia vine 10 g, Bupleurum chinense 2 g, Rehmannia glutinosa 10 g; each group of formulas was weighed, pulverized, and passed through a 40-mesh sieve.

[0012] Example 2: Morinda officinalis 3 g, Acacia vine 3 g, Bupleurum chinense 3 g, Rehmannia glutinosa 3 g; each group of formulas was weighed, pulverized, and passed through a 40-mesh sieve.

[0013] Example 3: Morinda officinalis 10 g, Acacia vine 10 g, Bupleurum chinense 5 g, Rehmannia glutinosa 5 g; each group of formulas was weighed, pulverized, and passed through a 40-mesh sieve.

[0014] Example 4: Morinda officinalis 5 g, Acacia vine 5 g, Bupleurum chinense 10 g, Rehmannia glutinosa 10 g; each group of formulas was weighed, pulverized, and passed through a 40-mesh sieve.

[0015] Example 5: Morinda officinalis 5 g, Acacia vine 10 g, Bupleurum chinense 10 g, Rehmannia glutinosa 5 g; each group of formulas was weighed, pulverized, and passed through a 40-mesh sieve.

[0016] Compared with the prior art, the present invention has the following beneficial technical effects:

[0017] The research results of the present invention show that it can relieve the phenomenon of vulva swelling and uterine enlargement in pigs poisoned by zearalenone, accelerate the recovery of the pigs' health, and reduce the economic losses caused by zearalenone toxin poisoning. Description of the Drawings

[0018] Figure 1 The manifestations of the vulva and secretions of pigs in the first group of Example 1 at the beginning of the experiment;

[0019] Figure 2 The manifestations of the vulva and secretions of pigs in the first group of Example 1 at the beginning of the experiment;

[0020] Figure 3 The manifestations of the vulva and secretions of pigs in the first group of Example 1 in the middle stage of the experiment;

[0021] Figure 4 Performance of the vulva and secretions of pigs at the end of the experiment in Example 1 group;

[0022] Figure 5 Performance of the vulva and secretions of pigs at the start of the experiment in the mycotoxin adsorbent group;

[0023] Figure 6 Performance of the vulva and secretions of pigs at the end of the experiment in the mycotoxin adsorbent group;

[0024] Figure 7 Performance of the vulva and secretions of pigs at the end of the experiment in the blank control group;

[0025] Figure 8 Vulva symptoms of piglets born to sows in Example 1 group;

[0026] Figure 9 Vulva symptoms of piglets born to sows in the mycotoxin adsorbent group;

[0027] Figure 10 Vulva symptoms of piglets born to sows in the blank control group. Detailed implementation method

[0028] According to the following examples, the present invention can be better understood. However, those skilled in the art can easily understand that the content described in the examples is only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0029] Test Example 1: Component screening test of the pharmaceutical composition

[0030] Detection indexes: Detection was carried out using body weight, uterine index and estrogen content (E2) as indexes;

[0031] Experimental method: Administration was carried out after successful establishment of the model by gavage with a dose of 1.00 mg / kg·bw for 10 consecutive days.

[0032] Experimental animals: Kunming mice, 20 - 22 g.

[0033] Test results: The specific values are shown in the following table. To more directly and obviously evaluate the drug effect, the year-on-year index is used for data standardization. Year-on-year index = prescription group / model group.

[0034] Table 1 Prescription drug composition

[0035]

[0036] Table 2 Grouping and administration

[0037]

[0038] The pharmacological effects were calculated and analyzed using the difference from the model group as the index. The specific results are shown in Table 3 below:

[0039] Table 3 Results of the optimization and screening test

[0040]

[0041] Result analysis:

[0042] In this study, the orthogonal t-value method was used for the formulation design based on modern pharmacological research. The test results showed that Morinda officinalis and Acacia concinna were the two main drugs with significant anti-estrogenic effects, while Bupleurum chinense and Rehmannia glutinosa had insignificant effects (adjuvant drugs), and Epimedium brevicornu, Glycyrrhiza uralensis, Angelica sinensis, and Pueraria lobata had adverse effects; Ligusticum chuanxiong, Zingiber officinale var. recens, and Carthamus tinctorius had no obvious effects.

[0043] The optimized prescription combination is: Morinda officinalis, Acacia concinna, Bupleurum chinense, and Rehmannia glutinosa. The combination of these four drugs can achieve the highest anti-estrogenic effect.

[0044] Test Example 2: Clinical effects of the pharmaceutical composition

[0045] Materials and methods

[0046] Mycotoxin binder and test animals

[0047] Example 1 was self-made, and a commercial mycotoxin binder (mainly composed of montmorillonite) was used as the control; pregnant sows close to parturition were provided by a pig farm in Luoyang. All test pigs had a history of eating moldy feed, and after quantitative detection, they were found to contain ZEA toxin, with clinical manifestations of enlarged vulva.

[0048] Clinical effect verification test

[0049] Nine pregnant sows close to parturition with similar parity, body weight, and ZEA poisoning manifestations were randomly divided into 3 groups, with 3 pigs in each group. They were raised separately and numbered as Example 1 group, mycotoxin binder control group, and blank control group. The specific operations are shown in Table 4. All groups were continuously administered for 17 days. When adding the drugs, they should be fully stirred to ensure thorough mixing. After administration, the vulva status of the test pigs (including redness, swelling, and secretions), daily average feed intake, farrowing rate, abortion rate, number of live piglets per litter, litter weight, feed-to-meat ratio, and health status were carefully observed and recorded every day.

[0050] Table 4 Clinical effect verification of the traditional Chinese medicine mycotoxin binder

[0051]

[0052] Results and analysis

[0053] Observation of vulva status

[0054] The results are shown in Table 5. As can be seen from Table 5, in the Example 1 group, the pigs had clinical disease manifestations in the vulva and secretions at the beginning of the test (Figure 1 )( Figure 2 ), the vulvar swelling was reduced after the 8th and 9th days of feeding ( Figure 3 ), and the vulvar swelling and secretions disappeared after the 17th day of feeding ( Figure 4 ); It is indicated that Example 1 has a relatively obvious effect on ZEA poisoning.

[0055] In the mycotoxin adsorbent group, the vulvar swelling of each pig was relatively severe at the beginning of the experiment ( Figure 5 ); The symptoms were reduced at the end of the experiment ( Figure 6 ), but it was relatively more severe than that in the Example 1 group, indicating that the mycotoxin adsorbent has a detoxifying effect on pigs poisoned by ZEA, but the effect is not as obvious as that of Example 1.

[0056] In the blank control group, the change in vulvar swelling of pigs was not obvious from the beginning to the end of the experiment, and the clinical symptoms were only slightly reduced ( Figure 7 ). The self-healing speed of pigs without using the mycotoxin adsorbent product after poisoning is slow.

[0057] Table 5 Record form of vulvar status

[0058]

[0059] Note 1:

[0060] (1) None: There are no symptoms in the vulva, recorded as "0 points";

[0061] (2) Slight: There are very slight and imperceptible symptoms in the vulva, which do not affect daily activities, feed intake and weight gain, recorded as "1 point";

[0062] (3) Moderate: Slight symptoms can be observed in the vulva, but there is no great interference with normal daily activities and production performance, recorded as "2 points";

[0063] (4) Slightly more: Obvious symptoms can be observed in the vulva, which have obvious interference with daily activities and production performance, recorded as "3 points";

[0064] (5) Severe: There are severe symptoms in the vulva, which have great interference with daily activities and production performance and affect production performance, recorded as "4 points";

[0065] Determination of production performance-related indicators

[0066] The results are shown in Table 6. It can be seen from Table 6 that the farrowing rates of the three experimental groups are all 100%, and no abortions occurred. The litter survival rates of all pigs in the Example 1 group and the mycotoxin adsorbent group are both 100%, and the litter survival rates of the control group are 90.9%, 100% and 83.3% respectively; The average litter weight is the highest in the Example 1 group and the lowest in the control group.

[0067] The pigs in Example 1 group gave birth on the 14th, 16th, and 31st days of feeding respectively, and the vulvas of the piglets born were normal ( Figure 8 ); the pigs in the mycotoxin adsorbent group gave birth on the 13th, 17th, and 31st days of feeding respectively, and the vulvas of the piglets born had slight swelling ( Figure 9 ); in the blank control group, pigs C1, C2, and C3 gave birth on the 13th, 17th, and 31st days of feeding respectively, and the vulvas of the piglets born had swelling ( Figure 10 ).

[0068] Table 6 Determination of related indexes of production performance

[0069]

[0070] Conclusions and Discussions

[0071] The screening of the formula is crucial for preventing porcine ZEA poisoning. The results of the clinical verification test of Example 1, which is composed of traditional Chinese medicines in combination, on sows poisoned by ZEA show that Example 1 has an obvious detoxification effect on ZEA. Considering the comprehensive evaluation results, Example 1 has a more obvious effect compared with the commonly used mycotoxin adsorbents in the existing market, and the present invention has prominent effect advantages.

Claims

1. A pharmaceutical composition for preventing and treating zearalenone poisoning in pigs, characterized in that: The invention comprises the following components in parts by weight: 1-15 parts of Morinda officinalis, 1-15 parts of Acacia scabra, 1-15 parts of Bupleurum chinense and 1-15 parts of Rehmannia glutinosa.

2. The pharmaceutical composition according to claim 1, characterized in that The invention comprises the following components in parts by weight: 3-10 parts of Morinda officinalis, 3-10 parts of Acacia scabra, 2-10 parts of Bupleurum chinense and 3-10 parts of Rehmannia glutinosa.

3. The pharmaceutical composition according to claim 2, characterized in that Contains the following components in parts by weight, 3 parts of Morinda officinalis, 10 parts of Acacia chinensis, 2 parts of Bupleurum chinense, and 10 parts of Rehmannia glutinosa; Or, 3 parts of Morinda officinalis, 3 parts of Acacia scabra, 3 parts of Bupleurum chinense, and 3 parts of Rehmannia glutinosa; Or, Morinda officinalis 10 parts, Acacia sylvestris 10 parts, Bupleurum 5 parts, Rehmannia glutinosa 5 parts; Or, Morinda officinalis 5 parts, Acacia sinensis 5 parts, Bupleurum 10 parts, Rehmannia glutinosa 10 parts; Alternatively, 5 parts of Morinda officinalis, 10 parts of Acacia sylvestris, 10 parts of Bupleurum chinense, and 5 parts of Rehmannia glutinosa.

4. The method for preparing the pharmaceutical composition according to any one of claims 1 to 3, characterized in that: The raw materials of Chinese medicine can be crushed with a pulverizer and premixed evenly.

5. Use of the pharmaceutical composition according to any one of claims 1 to 3 in the preparation of a drug for preventing and treating zearalenone poisoning in pigs.

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