Traditional Chinese medicine compound for treating endometritis of livestock and poultry, preparation method and application thereof

Abstract

The application discloses a traditional Chinese medicine compound for treating uterine endometritis of livestock and poultry and a preparation method and application thereof; raw materials of the traditional Chinese medicine compound include 25-35 parts of poria cocos, 15-25 parts of radix codonopsis, 10-20 parts of cyperus rotundus, 5-15 parts of white atractylodes, 15-25 parts of dried ginger, 5-15 parts of taraxacum and 15-25 parts of arctium lappa by weight percentage. The traditional Chinese medicine compound has a good treatment effect on uterine endometritis of livestock and poultry, and all the drugs used in the application are natural plants which can be fed and can effectively reduce side effects in the treatment of uterine endometritis.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of livestock and poultry traditional Chinese medicine, and particularly relates to a traditional Chinese medicine compound for treating endometritis of livestock and poultry, and a preparation method and application thereof. BACKGROUND

[0002] Endometritis is one of the common obstetric diseases in livestock and poultry. The disease has a high incidence, with an incidence of 20% to 40% in dairy cows, a wide range of prevalence, and is one of the main causes of infertility in livestock and poultry, increasing the breeding cost and culling rate, and causing huge economic losses to the breeding industry. Uterine flushing is a commonly used method for treating endometritis in dairy cows, but it also has disadvantages and limitations. First, this method can cause trauma and stress to the dairy cow. During the uterine flushing process, sensitive dairy cows may feel uncomfortable, and even lead to other health diseases; second, uterine flushing cannot completely remove all pathogens. Some pathogens may hide in the deep layer of the endometrium or form a biofilm, so that flushing cannot completely remove them, thereby affecting the treatment effect; third, uterine flushing can lead to secondary infection. If the operation is not proper or clean, the catheter inserted into the uterine cavity can further infect bacteria, which can lead to further infection of bacteria, increasing the risk of secondary infection; fourth, the time of uterine flushing is limited. This method needs to be treated during the specific periodic opening of the neck, and cannot forcibly insert the tube.

[0003] The commonly used treatment method for endometritis is also antibiotic treatment, but this method still has the following disadvantages:

[0004] First, the problem of drug resistance: long-term use of antibiotics can lead to drug resistance of dairy cows to such drugs, thereby reducing the treatment effect. The development of drug resistance will increase the difficulty of treatment and can lead to recurrence of the disease;

[0005] Second, the problem of residues and food safety: after the metabolism of antibiotics in dairy cows, residues can be left in the milk, meat and other foods of dairy cows, causing food safety problems. Long-term consumption of foods containing antibiotic residues can pose potential risks to human health;

[0006] Third, harm to the health of dairy cows: long-term use of antibiotics inevitably destroys the beneficial flora in the intestinal tract of dairy cows, leading to imbalance of intestinal microecology. This also has a negative impact on the health and immune system of dairy cows, reduces their resistance, and makes them more susceptible to infection by other pathogens. In addition, antibiotics can also cause a burden on the organs such as liver and kidney of dairy cows;

[0007] Fourth, the problem of environmental pollution: the large-scale use of antibiotics can lead to the accumulation of antibiotics in the environment, causing environmental pollution and having a negative impact on the ecosystem.

[0008] Hormone treatment for endometritis in dairy cows also has disadvantages and limitations:

[0009] First, side effects and risks: Hormone therapy may lead to hormonal imbalance, metabolic disorders, immunosuppression, etc. Long-term use or abuse of hormones may have a negative impact on the health and productivity of dairy cows.

[0010] Second, its applicability is limited: hormone therapy is not suitable for all dairy cows, especially those with other health problems, hormone sensitivity, or whose physical condition is unsuitable for hormone intervention. Therefore, when using hormone therapy, it is necessary to conduct an assessment and selection based on the specific circumstances.

[0011] Third, hormone therapy may mask underlying problems: while it may temporarily relieve symptoms, it does not cure the root cause of endometritis. If the underlying cause and pathological changes are not addressed, the disease may relapse or worsen.

[0012] Traditional Chinese medicine (TCM) treatments are numerous and varied in dosage forms, with minimal side effects on animals. Currently, Chinese invention patent CN116870080A discloses a TCM compound for treating endometritis in beef cattle. The compound contains, by weight, 30-40% Angelica sinensis, 20-30% Leonurus japonicus, 10-20% black soybean, 10-20% Ligusticum chuanxiong, 5-10% Rehmannia glutinosa, 5-10% Paeonia lactiflora, 5-10% Alisma plantago-aquatica, 1-4% Carthamus tinctorius, 5-10% Morinda officinalis, and 1-4% brown sugar. However, this formula uses high-cost medicinal materials, resulting in high treatment costs and slow effects, requiring a prolonged treatment period to demonstrate efficacy. Furthermore, its complex composition and cumbersome preparation significantly increase treatment costs.

[0013] Therefore, it is of great significance to develop traditional Chinese medicine preparations that are low in cost and have faster effects. Summary of the Invention

[0014] The purpose of this invention is to overcome the shortcomings of the prior art and provide a traditional Chinese medicine compound for treating endometritis in livestock and poultry, its preparation method, and its application.

[0015] To achieve the above objectives, the technical solution designed by the present invention is as follows:

[0016] This invention provides a traditional Chinese medicine compound for treating endometritis in livestock and poultry. The raw materials of the traditional Chinese medicine compound include, by weight, the following ingredients: 25-35 parts of Poria cocos, 15-25 parts of Codonopsis pilosula, 10-20 parts of Cyperus rotundus, 5-15 parts of Atractylodes macrocephala, 15-25 parts of dried ginger, 5-15 parts of Taraxacum mongolicum, and 15-25 parts of Arctium lappa.

[0017] Furthermore, the raw materials of the traditional Chinese medicine compound, by weight, include 28-32 parts of Poria cocos, 18-22 parts of Codonopsis pilosula, 13-17 parts of Cyperus rotundus, 8-12 parts of Atractylodes macrocephala, 18-22 parts of dried ginger, 8-12 parts of dandelion, and 18-22 parts of Arctium lappa.

[0018] Furthermore, the raw materials of the Chinese herbal compound, by weight, include 30 parts of Poria cocos, 20 parts of Codonopsis pilosula, 15 parts of Cyperus rotundus, 10 parts of Atractylodes macrocephala, 20 parts of dried ginger, 10 parts of dandelion, and 20 parts of Arctium lappa.

[0019] Furthermore, the raw materials of the Chinese herbal compound, by weight, include 30 parts of Poria cocos, 18 parts of Codonopsis pilosula, 15 parts of Cyperus rotundus, 10 parts of Atractylodes macrocephala, 18 parts of dried ginger, 8 parts of dandelion, and 20 parts of Arctium lappa.

[0020] This invention also provides a method for preparing the above-mentioned traditional Chinese medicine compound for treating endometritis in livestock and poultry, comprising the following steps:

[0021] 1) Weigh out the following ingredients according to the above weight ratio: Poria cocos, Codonopsis pilosula, Cyperus rotundus, Atractylodes macrocephala, dried ginger, Taraxacum mongolicum, and Arctium lappa.

[0022] 2) Mix all Chinese herbs except Cyperus rotundus and soak them in water. Heat over high heat until boiling. Count from the time of boiling, pour out the first decoction after heating, add warm water and Cyperus rotundus, and heat to obtain the second decoction.

[0023] 3) Mix the two medicinal solutions to obtain a traditional Chinese medicine compound.

[0024] The present invention also provides an application of the above-mentioned traditional Chinese medicine compound in the preparation of traditional Chinese medicine preparations for endometritis in livestock and poultry.

[0025] The present invention also provides a traditional Chinese medicine preparation, which includes the above-mentioned traditional Chinese medicine compound.

[0026] Furthermore, the traditional Chinese medicine preparation also includes pharmaceutically acceptable excipients.

[0027] Furthermore, the excipients are any one or more of vitamin C, sorbitol, mannitol, xylitol, fructose, amino acids, meglumine, dextrin, magnesium stearate, and sucrose.

[0028] Furthermore, the traditional Chinese medicine preparation is an oral liquid or granules.

[0029] The pharmacological properties of this invention are as follows:

[0030] This formula uses Poria cocos as the main ingredient to promote diuresis and eliminate dampness, strengthen the spleen and calm the mind, improve the body's resistance, and detoxify and expel pathogens. Dried ginger, Codonopsis pilosula, and Arctium lappa are used as assistant ingredients to relieve exterior syndromes and dispel cold, warm the middle jiao and detoxify, strengthen the spleen and benefit the lungs, nourish blood and generate body fluids. Cyperus rotundus and Atractylodes macrocephala are used as adjuvant ingredients to soothe the liver and relieve depression, regulate qi and relieve chest tightness, regulate menstruation and relieve pain, strengthen the spleen and benefit qi, dry dampness and promote diuresis. Dandelion is used as the guiding ingredient to clear heat and detoxify, reduce swelling and dissipate nodules, and promote urination and relieve strangury.

[0031] The beneficial effects of this invention are:

[0032] 1. The traditional Chinese medicine compound of the present invention can effectively treat endometritis in livestock and poultry, and also has a significant relieving effect on the symptoms of endometrial epithelial cell inflammation. It can be effective in 2 days, and is convenient to treat by oral administration.

[0033] 2. The traditional Chinese medicine components contained in the compound formula of the present invention are all of the 115 kinds of feed-grade traditional Chinese medicine additives, which comply with relevant Chinese policies and can be used as feed additives for a long time. The compound formula has few side effects, low cost, and low treatment cost. Attached Figure Description

[0034] Figure 1 Image showing the changes in body weight and gross morphology of the uterus in mice with endometritis before and after treatment;

[0035] Figure 2 A pathological section of the mouse uterus;

[0036] Figure 3 A pathological scoring image of the mouse uterus (200μm);

[0037] Figure 4 Image showing inflammatory markers in mouse uterine tissue and serum. Detailed Implementation

[0038] The present invention will now be described in further detail with reference to specific embodiments, so that those skilled in the art can understand it.

[0039] Example 1

[0040] The raw materials of the traditional Chinese medicine compound 1 used to treat endometritis in livestock and poultry are: Poria cocos 30g, Codonopsis pilosula 20g, Cyperus rotundus 15g, Atractylodes macrocephala 10g, dried ginger 20g, Taraxacum mongolicum 10g, and Arctium lappa 20g.

[0041] All the Chinese medicinal materials mentioned above were purchased from Wuhan Zhihe Qingqiang Pharmacy Co., Ltd., and were accurately weighed before being used in subsequent experiments.

[0042] The preparation method of the above-mentioned traditional Chinese medicine compound 1 includes the following steps:

[0043] 1) Weigh out 30g of Poria cocos, 20g of Codonopsis pilosula, 15g of Cyperus rotundus, 10g of Atractylodes macrocephala, 20g of dried ginger, 10g of Taraxacum mongolicum, and 20g of Arctium lappa. Mix all the herbs except Cyperus rotundus and soak them in cold water (distilled water) for 20 minutes, with the water level 2-3cm above the herbs (or according to a material-to-liquid ratio of 1:10, w / v). Heat over high heat until boiling, and from the boiling point, heat for 25 minutes. Pour out the first decoction, add warm water and Cyperus rotundus, add an appropriate amount of warm water, and heat for 15 minutes to obtain the second decoction.

[0044] 2) The two decoctions (water decoctions) are mixed to obtain the Chinese herbal compound 1.

[0045] Example 2

[0046] The traditional Chinese medicine compound 2 prepared in this embodiment is basically the same as that in Example 1, except that:

[0047] The raw materials of the above-mentioned Chinese herbal compound 2, by weight, include 32 parts of Poria cocos, 18 parts of Codonopsis pilosula, 16 parts of Cyperus rotundus, 9 parts of Atractylodes macrocephala, 18 parts of dried ginger, 8 parts of dandelion, and 18 parts of Arctium lappa.

[0048] Example 3

[0049] The traditional Chinese medicine compound 3 prepared in this embodiment is basically the same as that in Example 1, except that:

[0050] The raw materials of the above-mentioned Chinese herbal compound 4, by weight, include 28 parts of Poria cocos, 18 parts of Codonopsis pilosula, 16 parts of Cyperus rotundus, 10 parts of Atractylodes macrocephala, 18 parts of dried ginger, 8 parts of dandelion, and 20 parts of Arctium lappa.

[0051] Example 4

[0052] The traditional Chinese medicine compound 4 prepared in this embodiment is basically the same as that in Example 1, except that:

[0053] The raw materials of the above-mentioned Chinese herbal compound 4, by weight, include 30 parts of Poria cocos, 18 parts of Codonopsis pilosula, 15 parts of Cyperus rotundus, 10 parts of Atractylodes macrocephala, 18 parts of dried ginger, 8 parts of dandelion, and 20 parts of Arctium lappa.

[0054] Example 5

[0055] The traditional Chinese medicine compound 5 prepared in this embodiment is basically the same as that in Example 1, except that:

[0056] The raw materials of the above-mentioned Chinese herbal compound 5, by weight, include 35 parts of Poria cocos, 15 parts of Codonopsis pilosula, 20 parts of Cyperus rotundus, 5 parts of Atractylodes macrocephala, 25 parts of dried ginger, 15 parts of Taraxacum mongolicum, and 15 parts of Arctium lappa.

[0057] Example 6

[0058] The traditional Chinese medicine compound 6 prepared in this embodiment is basically the same as that in Example 1, except that:

[0059] The raw materials of the above-mentioned Chinese herbal compound 6, by weight, include 25 parts of Poria cocos, 25 parts of Codonopsis pilosula, 10 parts of Cyperus rotundus, 15 parts of Atractylodes macrocephala, 15 parts of dried ginger, 5 parts of Taraxacum mongolicum, and 25 parts of Arctium lappa.

[0060] Example 7

[0061] A traditional Chinese medicine compound granule is prepared by the following steps:

[0062] The traditional Chinese medicine compound 1 obtained in Example 1 was heated and concentrated to a thick paste (5 - 10 g), and at the same time, 50 g each of dextrin and sucrose were weighed and mixed as excipients. The thick paste was slowly poured into the excipients in a large evaporating dish and mixed to form soft materials (the softness and hardness of the soft materials should be appropriate, preferably "forming a ball when held in the hand and dispersing when gently pressed"). Then, granulation was carried out by extrusion through a 18-mesh stainless steel sieve, and the granules were pressed into a square porcelain dish. They were placed in an oven and dried at 40 - 60 °C for about 1 h. After taking them out and weighing, screening was carried out again with 12-mesh and 60-mesh stainless steel sieves. Finally, weighing was carried out again, and the granule yield was calculated. This granule has good palatability for animals, is easy to store, and can be directly added to feed.

[0063] Verification effect of the traditional Chinese medicine compound prepared in the above example:

[0064] 1. Verify the side effects of traditional Chinese medicine compound 1

[0065] The traditional Chinese medicine compound 1 prepared in Example 1 was gavaged to mice at the drug doses of 250, 500, and 1000 mg / kg. After 7 days of administration, the median lethal dose of the mice was calculated; the results showed that when the administration dose was increased to 1000 mg / kg, no death occurred in the mice, and there were no significant differences in the food intake, water intake, body weight, and body weight growth rate between the experimental group mice and the control group mice. The LD50 of this formula was greater than 1000 mg / kg. This range far exceeded the commonly used effective dose of this formula. It indicates that this compound has no side effects at effective concentrations.

[0066] 2. Preliminary verification of the effectiveness of traditional Chinese medicine compounds 1 - 4

[0067] (1) Experimental materials

[0068] 1.1 Drugs: Traditional Chinese medicine compounds 1, 2, 3, and 4 were concentrated to 1 g / mL with a rotary evaporator; normal saline.

[0069] 1.2 Animals: Male Kunming mice (SPF grade), weighing 20 ± 2 g, were purchased from Huazhong Agricultural University, license number SCXK(E)2020 - 0019, and the license number for the experimental unit's use was SYXK(E)2019 - 0044. This experiment was approved by the Scientific Ethics Committee of Huazhong Agricultural University, ethics number HZAUMO - 2023 - 0146. All mice were kept in an environment with a temperature of 22 ± 1 °C and a humidity of 55 ± 5%. Keep 12 hours of lighting / 12 hours of darkness, evenly irradiated with natural light, 6 mice per cage, and the mice can freely ingest food and water.

[0070] (2) Experimental methods

[0071] Thirty-six mice were randomly divided into six groups, with no significant difference in body weight among the groups. Each group consisted of six mice: a control group, a model group, F1 group (compound 1), F2 group (compound 2), F3 group (compound 3), and F4 group (compound 4). The mice were acclimatized for 7 days before the experiment began. Modeling: Except for the control group, 50 μL of 1 mg / mL LPS was injected into the mouse vagina via a gavage needle, inserted approximately 0.5 cm, and infused into the uterus to induce an endometritis model. Drug treatment: One day later, all groups began treatment. The control and model groups were administered 150 μL of physiological saline by gavage, while groups F1, F2, F3, and F4 were administered the traditional Chinese medicine oral solution by gavage for 2 days. During the treatment period, mice were closely monitored for phenotypic indicators. Affected mice should exhibit lethargy, reduced activity, decreased appetite, frequent urination attempts without urine output, and discharge of copious yellowish-white or reddish-gray mucous or purulent secretions from the vulva with a foul odor; severe cases may present with brownish-red mucous discharge. Sample collection: After treatment, blood was collected from the eyeballs, and serum was separated by centrifugation at 6000 rpm for 5 minutes to detect serum indicators. Mice were euthanized by cervical dislocation, and the abdominal cavity was opened. The uterus was removed, weighed, and the uterine index was calculated. A portion of the uterus was fixed with 4% paraformaldehyde, and another portion was stored at -80℃ for later analysis.

[0072] (3) Experimental Results

[0073] Before LPS stimulation, there was no significant difference in body weight among the groups of mice, but 3 days after LPS challenge, a significant decrease in body weight was observed in the challenged mice. Figure 1 A) Among them, the weight loss of mice in groups F1 and F4 was significantly different from that in the model group (P<0.05), but not significantly different from that in the blank group. However, the weight loss of mice in groups F2 and F3 was not significantly different from that in the model group. This suggests that both compound 1 and compound 4 have good therapeutic effects. Anatomical images of the uterus also show obvious redness and swelling in the model group and F2 group, obvious redness in the F3 group, only slight redness in the F4 group, and the uterine condition in the F1 group is closest to that of the control group. Figure 1 B). In summary, these results preliminarily suggest that compound F1 to F4 all have certain therapeutic effects on endometritis in mice, with compound F1 and F4 showing significant efficacy.

[0074] Histopathological analysis showed that compound F4 had the best therapeutic effect. In the control group mice, the endometrium was intact, the structure was clear, the boundary between the myometrium and endometrium was distinct, and the uterine cavity was relatively large. Figure 2 A); while the uterus of the model group mice showed obvious swelling (A); Figure 2 B), the residual area of ​​the uterine cavity was small, accompanied by inflammatory cell infiltration, and the pathological score was significantly different from that of the control group. Figure 3 The uterus of mice in groups F1, F2, and F3 still showed some degree of swelling, while the swelling in mice in group F4 subsided. Figure 2The pathological scores of F4 patients were significantly different from those of the model group. Therefore, from a pathological analysis perspective, F4 patients showed the best treatment efficacy.

[0075] Analysis of inflammatory markers revealed that F4 was the most effective treatment for endometritis in mice. In uterine tissue and serum, the levels of MPO and NO in the model group mice were significantly higher than in the control group, and both decreased after treatment. The decrease in MPO and NO levels was particularly significant after treatment with F1 and F4, indicating that F4 was more effective than F1. Figure 4 ).

[0076] In summary, this invention can be used as a traditional Chinese medicine compound reagent for treating endometritis.

[0077] All other parts not described in detail are existing technologies. Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine for treating endometritis in livestock and poultry, characterized in that: The raw materials of the Chinese medicine are composed of 30-32 parts of Poria cocos, 18-22 parts of Codonopsis pilosula, 13-17 parts of Cyperus rotundus, 8-12 parts of Atractylodes macrocephala, 18-22 parts of dried ginger, 8-12 parts of dandelion and 18-22 parts of burdock seed by weight.

2. The traditional Chinese medicine for treating endometritis in livestock and poultry according to claim 1, characterized in that: The raw materials of the Chinese medicine are composed of 30 parts Poria cocos, 20 parts Codonopsis pilosula, 15 parts Cyperus rotundus, 10 parts Atractylodes macrocephala, 20 parts dried ginger, 10 parts dandelion and 20 parts burdock seed by weight.

3. The traditional Chinese medicine for treating endometritis in livestock and poultry according to claim 1, characterized in that: The raw materials of the Chinese medicine are composed of 30 parts by weight of Poria cocos, 18 parts of Codonopsis pilosula, 15 parts of Cyperus rotundus, 10 parts of Atractylodes macrocephala, 18 parts of dried ginger, 8 parts of dandelion and 20 parts of Arctium lappa.

4. A method for preparing a traditional Chinese medicine for treating endometritis in livestock and poultry as described in any one of claims 1 to 3, characterized in that: Includes the following steps: 1) Weigh out the following ingredients according to the above weight ratio: Poria cocos, Codonopsis pilosula, Cyperus rotundus, Atractylodes macrocephala, dried ginger, Taraxacum mongolicum, and Arctium lappa. 2) Mix all Chinese herbs except Cyperus rotundus and soak them in water. Heat over high heat until boiling. Count from the time of boiling, pour out the first decoction after heating, add warm water and Cyperus rotundus, and heat to obtain the second decoction. 3) Mix the two solutions to obtain traditional Chinese medicine.

5. The use of the traditional Chinese medicine as described in any one of claims 1 to 3 in the preparation of a traditional Chinese medicine preparation for treating endometritis in livestock and poultry.

6. A traditional Chinese medicine preparation, characterized in that: The traditional Chinese medicine preparation includes the traditional Chinese medicine as described in any one of claims 1 to 3.

7. The traditional Chinese medicine preparation according to claim 6, characterized in that: The traditional Chinese medicine preparation also includes pharmaceutically acceptable excipients.

8. The traditional Chinese medicine preparation according to claim 7, characterized in that: The excipients are any one or more of vitamin C, sorbitol, mannitol, xylitol, fructose, amino acids, meglumine, dextrin, magnesium stearate, and sucrose.

9. The traditional Chinese medicine preparation according to any one of claims 6 to 8, characterized in that: The traditional Chinese medicine preparation is an oral liquid or granule.

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