A heat-clearing and cough-stopping traditional Chinese medicine preparation for livestock and poultry and a preparation method thereof

Abstract

This invention provides a traditional Chinese medicine preparation for clearing heat and relieving cough in livestock and poultry, comprising the following raw materials: mulberry bark, anemarrhena rhizome, bitter almond, angelica root, gypsum, aromatic organic acids, gelatin, and a suspension mother liquor. The effective medicinal components in the oral liquid are presented in the form of sustained-release microcapsules. These microcapsules use gypsum with a mixed extract of mulberry bark, anemarrhena rhizome, bitter almond, and angelica root as the core material, and aromatic organic acids and gelatin as the wall material, prepared using an emulsification cross-linking method. This invention prepares sustained-release microcapsules from the raw materials with a pronounced bitter taste in the traditional Chinese medicine preparation. This not only prolongs the drug's action time and improves its utilization rate, but also, the aromatic organic acids on the surface of the microcapsules impart a refreshing aroma to the oral liquid, making it easier for livestock and poultry to consume.

Description

Technical Field

[0001] This invention relates to the field of veterinary drug technology, and in particular to a traditional Chinese medicine preparation for livestock and poultry that clears heat and relieves cough, and its preparation method. Background Technology

[0002] With the improvement of people's living standards, dietary structures have improved, and meat has become an indispensable part of people's daily diet. Among various meat products, chicken is the most popular, which has also promoted the development of my country's animal husbandry industry. Broiler chicken farming is profitable and low-risk, and there are numerous chicken farms of all sizes throughout the country. Chickens are raised using both pen-raising and free-range methods. Disease control and prevention are effective measures to reduce farming risks. Bronchitis in chickens is caused by infection with infectious mycoviruses, which damage the respiratory system and kidney tissue. This disease has a high incidence rate and is highly contagious, so it is necessary to strengthen the prevention and control of bronchitis in chicken farming.

[0003] Based on previous diagnosis and treatment of bronchitis in chickens, and analysis of its symptoms, the following conclusions have been drawn: In the early stages of infection with the bronchitis virus, chickens exhibit lethargy, loss of appetite or poor appetite, diarrhea, and increased nasal discharge. Initially, infected chickens will show tearing and swollen eyelids. As the disease progresses, in more severe stages of bronchitis, chickens will experience severe difficulty breathing, accompanied by rales and coughing. Furthermore, during illness, chickens may experience elevated body temperature, slowed growth, and emaciation.

[0004] In animal husbandry, vaccination is the most effective way to prevent disease, while antibiotics are the fastest way to treat it. However, in the past decade or so, the problems caused by the overuse of antibiotics have threatened human safety and health. Food safety issues in the livestock industry are mainly manifested in problems such as drug resistance, drug residues, decreased animal immune function, frequent outbreaks of livestock and poultry diseases, accelerated viral mutation, and the emergence of superbugs. Reducing, limiting, or even eliminating antibiotics in livestock farming has become a key task strongly promoted by the government. The environmentally friendly development of livestock farming is a hurdle that the industry must overcome.

[0005] Traditional Chinese medicine (TCM), often called "natural antibiotics," not only contains flavonoids, saponins, and other bioactive components that directly inhibit or kill pathogenic microorganisms, but more importantly, it contains polysaccharides and peptides that repair and regulate the body's disease-fighting abilities, mobilizing the body's stress response and enhancing its immune function and disease defense capabilities. Due to the multi-target and multi-stage antibacterial characteristics of TCM, it is generally less likely to induce drug resistance during use, and it remains effective even against antibiotic-resistant bacteria.

[0006] Patent document CN107714822A discloses a traditional Chinese medicine composition for livestock and poultry with the effects of resolving phlegm, relieving cough, and calming asthma. The components and their weight ratios are as follows: Poria cocos 10-40 parts; Citrus medica var. sarcodactylis 10-40 parts; Trichosanthes kirilowii seed 10-40 parts; Lysimachia christinae 5-30 parts; Scutellaria baicalensis 5-30 parts; Inula japonica 5-30 parts; Morus alba leaf 5-30 parts; Glycyrrhiza uralensis 10-30 parts; Ziziphus jujuba seed 10-30 parts. It has the effects of clearing the lungs and resolving phlegm, calming asthma, and soothing the nerves and relieving stress. However, this traditional Chinese medicine composition has a relatively large number of components, which may be difficult for livestock and poultry with compromised bodily functions to absorb effectively, leading to prolonged treatment time and increased breeding costs. Summary of the Invention

[0007] In order to solve some problems existing in the prior art, the present invention provides a traditional Chinese medicine preparation for clearing heat and relieving cough in livestock and poultry and its preparation method.

[0008] A traditional Chinese medicine preparation for clearing heat and relieving cough in livestock and poultry comprises the following raw materials: mulberry bark, anemarrhena rhizome, bitter almond, angelica root, gypsum, aromatic organic acid, gelatin, and suspension mother liquor; wherein, the mulberry bark, anemarrhena rhizome, bitter almond, angelica root, and gypsum are prepared into microcapsule core material through extraction and adsorption, and the aromatic organic acid and gelatin are prepared into microcapsule wall material, and the two are combined through emulsification and cross-linking to form sustained-release microcapsules.

[0009] In some embodiments of the present invention, the suspension mother liquor is at least one of purified water, ethyl oleate, soybean oil, corn oil, and sesame oil.

[0010] In some embodiments of the present invention, the aromatic organic acid is at least one of p-hydroxycinnamic acid, caffeic acid, ferulic acid, and sinapic acid.

[0011] In some embodiments of the present invention, the preparation process of the sustained-release microcapsules includes the following steps: S1: Gypsum pretreatment: Weigh the gypsum, grind it, sieve out the gypsum with a particle size of 0.1-0.2μm, add acidic EDTA solution, sonicate at a constant temperature in a water bath at 50-70℃ for 30-45min, filter, dry under reduced pressure, and set aside for later use. S2: Extraction of medicinal liquid: Weigh out mulberry bark, anemarrhena rhizome, bitter almond, and angelica root, grind them into powder and mix them evenly. Put them into an extraction tank, add ethanol for reflux treatment, and after treatment for 2-4 hours, take out the powder and dry it. Then perform ultrasonic cell pulverization, add distilled water for ultrasonic treatment, filter, and concentrate by rotary evaporation. S3: Core material preparation: Weigh the concentrated drug solution obtained in S2, place it in a stoppered conical flask, add the pretreated gypsum from S1, fill with inert gas, seal tightly, stir at 1500-2000 r / min for 30 min, filter, dry under reduced pressure at 30-50℃, and place in a sealed container for later use; S4: Weigh gelatin and aromatic organic acid, add a small amount of deionized water, keep the temperature at 50-60℃, and stir until fully swollen; weigh the core material obtained in S3 and add it to the gelatin solution, stirring to form a suspension as the aqueous phase; mix liquid paraffin and Span to form the oil phase; slowly add the aqueous phase to the oil phase, continue stirring, add isopropanol for dehydration for 3-5 minutes, and cure with glutaraldehyde for 5-10 minutes. Stir, place at 4-6℃ overnight, wash three times with isopropanol and water respectively, filter and dry to obtain the sustained-release microcapsules.

[0012] Further, in S1, the acidic EDTA is prepared by mixing 1.5-2.5mM hydrochloric acid solution and EDTA at a mixing ratio of 3.5-4ml:1mg; the mixing ratio of gypsum and acidic EDTA is 1g:20-25ml.

[0013] Furthermore, in S2, the ultrasonic power is 800-1000W, and the ultrasonic treatment lasts for 30-45 minutes; the mass ratio of the powder to distilled water is 1:20-30.

[0014] Furthermore, in S3, the mass ratio of the concentrated medicinal solution to the pretreated gypsum is 1-5:1.

[0015] Furthermore, in S4, the mixing ratio of the core material to the gelatin solution is 1:50-100; the volume of the liquid paraffin used is 0.5-0.7 times that of the gelatin solution.

[0016] Further, in S4, the mass concentration of gelatin in the gelatin solution is 10-20%; the concentration of Span in liquid paraffin is 1.5-2.0%.

[0017] The preparation method of the above-mentioned traditional Chinese medicine preparation for clearing heat and relieving cough for livestock and poultry includes the following steps: mixing the prepared sustained-release microcapsules with the suspension mother liquor at a volume ratio of 2-5:10-18 at room temperature to obtain the traditional Chinese medicine preparation.

[0018] Beneficial effects: Compared with the prior art, the traditional Chinese medicine preparation provided by this invention has the following advantages: 1. The aromatic organic acids contained in the wall of the sustained-release microcapsules can significantly reduce the bitterness of the traditional Chinese medicine liquid, making it more palatable; more importantly, the presence of aromatic organic acids can indirectly promote the operation of the body's own immune system through chelation by gathering metal ions in the body, thus exhibiting an immune-enhancing effect. 2. By preparing sustained-release microcapsule core materials from Chinese medicinal herbs in different states of existence, the aroma emitted from the microcapsule walls not only increases the drug's orally applicability but also enhances the body's effective absorption rate of the drug. Detailed Implementation The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0019] Example 1 S1: Gypsum pretreatment: Weigh 10g of gypsum and grind it. Sift out 8g of gypsum with a particle size of 0.1-0.2μm. Add 160ml of acidic EDTA solution (350mL of 1.5mM hydrochloric acid solution contains 100mg EDTA). Sonicate at a constant temperature in a 50℃ water bath for 30min. Filter, dry under reduced pressure, and set aside for later use. S2: Extraction of medicinal liquid: Weigh 2g of mulberry bark, 3g of anemarrhena rhizome, 2g of bitter almond, and 5g of angelica root, grind them into powder and mix them evenly. Put them into an extraction tank, add 50ml of 70% ethanol and reflux for 2 hours. After treatment, take out the powder and dry it. Then perform ultrasonic cell disruption (800W, 45min), add 240ml of distilled water and sonicate. After filtration, concentrate by rotary evaporation. S3: Core material preparation: Weigh 15ml of the concentrated drug solution obtained in S2, place it in a stoppered conical flask, add 3g of the pretreated gypsum in S1, purge with nitrogen, seal tightly, stir at 1500r / min for 30min, filter, dry under reduced pressure at 30℃, and place in a sealed container for later use. S4: Weigh 2g of gelatin and 8g of p-hydroxycinnamic acid, add 18ml of deionized water, keep warm to 50℃, and stir until fully swollen; weigh 2g of the core material obtained in S3 and add it to 100ml of gelatin solution, stir to form a suspension as the aqueous phase; take 50ml of liquid paraffin and 0.87g of Span-80 and mix well as the oil phase; slowly add the aqueous phase to the oil phase, continue stirring, add isopropanol for dehydration for 3min, and cure with glutaraldehyde for 5min. Stir, place at 4℃ overnight, wash three times with isopropanol and water respectively, filter and dry to obtain the sustained-release microcapsules.

[0020] The obtained sustained-release microcapsules were mixed with ethyl oleate at a volume ratio of 2:10 at room temperature to obtain a traditional Chinese medicine preparation.

[0021] Example 2 S1: Gypsum pretreatment: Weigh 10g of gypsum and grind it. Sift out 8g of gypsum with a particle size of 0.1-0.2μm. Add 184ml of acidic EDTA solution (400mL of 2.0mM hydrochloric acid solution contains 100mg EDTA). Sonicate at a constant temperature in a 60℃ water bath for 30min. Filter, dry under reduced pressure, and set aside for later use. S2: Extraction of medicinal liquid: Weigh 3.5g of mulberry bark, 5g of anemarrhena rhizome, 3.5g of bitter almond, and 6.5g of angelica root, grind them into powder and mix them evenly. Put them into an extraction tank, add 50ml of 80% ethanol and reflux for 3 hours. Take out the powder and dry it. Then perform ultrasonic cell disruption (900W, 40min), add 462.5ml of distilled water and sonicate. After filtration, concentrate by rotary evaporation. S3: Core material preparation: Weigh 24 ml of the concentrated drug solution obtained in S2, place it in a stoppered conical flask, add 3 g of the pretreated gypsum from S1, purge with nitrogen, seal tightly, stir at 1700 r / min for 30 min, filter, dry under reduced pressure at 40℃, and place in a sealed container for later use. S4: Weigh 3g of gelatin and 10g of caffeic acid, add 17ml of deionized water, keep warm to 55℃, and stir until fully swollen; weigh 1g of the core material obtained in S3 and add it to 100ml of gelatin solution, stirring to form a suspension as the aqueous phase; take 60ml of liquid paraffin and 0.93g of Span-80 and mix well as the oil phase; slowly add the aqueous phase to the oil phase, continue stirring, add isopropanol for dehydration for 3min, and cure with glutaraldehyde for 5min. Stir, place at 5℃ overnight, wash three times with isopropanol and water respectively, filter and dry to obtain the sustained-release microcapsules.

[0022] The obtained sustained-release microcapsules were mixed with ethyl oleate at a volume ratio of 3:14 at room temperature to obtain a traditional Chinese medicine preparation.

[0023] Example 3 S1: Gypsum pretreatment: Weigh 10g of gypsum and grind it. Sift out 8g of gypsum with a particle size of 0.1-0.2μm. Add 184ml of acidic EDTA solution (400mL of 2.5mM hydrochloric acid solution contains 100mg EDTA). Sonicate at a constant temperature in a 70℃ water bath for 45min. Filter, dry under reduced pressure, and set aside for later use. S2: Extraction of medicinal liquid: Weigh 5g of mulberry bark, 7g of anemarrhena rhizome, 5g of bitter almond, and 8g of angelica root, grind them into powder and mix them evenly. Put them into an extraction tank, add 50ml of 80% ethanol and reflux for 3 hours. After treatment, take out the powder and dry it. Then perform ultrasonic cell disruption (1000W, 30min), add 750ml of distilled water and sonicate. After filtration, concentrate by rotary evaporation. S3: Core material preparation: Weigh 30ml of the concentrated drug solution obtained in S2, place it in a stoppered conical flask, add 3g of the pretreated gypsum in S1, fill with nitrogen, seal tightly, stir at 2000r / min for 30min, filter, dry under reduced pressure at 50℃, and place in a sealed container for later use. S4: Weigh 5g of gelatin and 10g of ferulic acid, add 20ml of deionized water, keep the temperature at 60℃, and stir until fully swollen; weigh 1g of the core material obtained in S3 and add it to 100ml of gelatin solution, stirring to form a suspension as the aqueous phase; take 70ml of liquid paraffin and 0.91g of Span-80 and mix well as the oil phase; slowly add the aqueous phase to the oil phase, continue stirring, add isopropanol for dehydration for 3min, and cure with glutaraldehyde for 5min. Stir, place at 6℃ overnight, wash three times with isopropanol and water respectively, filter and dry to obtain the sustained-release microcapsules.

[0024] The obtained sustained-release microcapsules were mixed with soybean oil at a volume ratio of 5:18 at room temperature to obtain a traditional Chinese medicine preparation.

[0025] Comparative Example 1 The preparation process is basically similar to that in Example 3, except that in S3, the pretreated lime is replaced with activated carbon.

[0026] Comparative Example 2 The preparation process is similar to that in Example 3, except that ferulic acid is not added.

[0027] Comparative Example 3 Mulberry bark, anemarrhena rhizome, bitter almond, angelica root, gypsum, and ferulic acid were mixed according to the dosage in Example 3, and decocted in water for 60 minutes to obtain a traditional Chinese medicine oral liquid.

[0028] Performance testing Forty-five hundred one-day-old white chicks were purchased from a chicken farm in the suburbs of Nanjing and were raised and managed according to standard procedures. Before the experiment, they were fed a complete feed without antibiotics and had free access to water. At 45 days of age, the chicks were divided into nine groups: six experimental groups, and three control groups (enrofloxacin control, infection control, and healthy control, without infection). Each chick in the experimental groups received 2 ml of enrofloxacin.

[0029] Test method: Artificial induction of chicken mycoplasma septicemia: Freeze-dried tubes of chicken mycoplasma septicemia (M·G) BG44T strain, after 4 passages, showed a growth turbidity of 10. 9 CFU / ml indicates mycoplasma infection. Except for the healthy control group, each chicken was inoculated with 1 ml of mycoplasma fluid in each of the left and right pectoral air sacs, and an additional 0.5 ml of mycoplasma fluid was administered via nasal drops.

[0030] Administration: Six hours after inoculating the experimental chickens with mycoplasma, each group of chickens was treated with the drug mixed into their feed for 3 consecutive days. Clinical symptoms were observed and dead chickens were necropsied before each administration to examine air sac lesions and determine the cause of death. The observation period was 15 days after the first administration.

[0031] Efficacy evaluation criteria: Mortality rate: During the trial, any chicken that showed typical symptoms of mycoplasma septicemia and died, and whose air sacs showed typical lesions upon necropsy, was considered dead. The mortality rate was calculated based on the number of deaths. Cure rate: Chickens whose mental state, appetite, and respiration returned to normal after medication during the trial period, and who no longer exhibited clinical symptoms such as coughing, rales, open-mouth breathing, or runny nose, were considered cured. The cure rate was calculated based on the number of cured chickens. Efficacy rate: After administration, the test chickens showed significant improvement in their spirit, appetite, and respiration, and their weight increased compared to before administration. The efficacy rate was calculated based on this.

[0032] Average weight gain: The weight gain was calculated based on the weight of the chickens before and after administration and at the end of the experiment, and the average weight gain for each group was calculated.

[0033] The treatment results are detailed in Table 1: Table 1 Treatment status of chickens in each group As shown in Table 1, the traditional Chinese medicine preparation provided by this invention has a higher curative efficiency for symptoms such as colds and coughs in chickens compared to traditional oral Chinese medicine liquids (Example 3 and Comparative Example 3). Furthermore, the results of Example 3 and Comparative Example 2 indicate that the presence of aromatic organic acids in the traditional Chinese medicine preparation promotes faster recovery and nutrient absorption in sick chickens. Therefore, it can be inferred that the traditional Chinese medicine preparation provided by this invention is more readily accepted by livestock and poultry than traditional oral Chinese medicine liquids, leading to increased intake and thus increased utilization of the active ingredients.

Claims

1. A traditional Chinese medicine preparation for clearing heat and relieving cough in livestock and poultry, characterized in that, It contains the following raw materials: mulberry bark, anemarrhena rhizome, bitter almond, angelica root, gypsum, aromatic organic acid, gelatin, and suspension mother liquor; wherein, the mulberry bark, anemarrhena rhizome, bitter almond, angelica root, and gypsum are prepared into microcapsule core material through extraction and adsorption, and the aromatic organic acid and gelatin are prepared into microcapsule wall material, and the two are combined through emulsification and cross-linking to form sustained-release microcapsules.

2. The traditional Chinese medicine preparation for clearing heat and relieving cough for livestock and poultry according to claim 1, characterized in that, The suspension mother liquor is at least one of purified water, ethyl oleate, soybean oil, corn oil, and sesame oil.

3. The traditional Chinese medicine preparation for clearing heat and relieving cough for livestock and poultry according to claim 1, characterized in that, The aromatic organic acid is at least one of p-hydroxycinnamic acid, caffeic acid, ferulic acid, and sinapic acid.

4. The traditional Chinese medicine preparation for clearing heat and relieving cough for livestock and poultry according to claim 1, characterized in that, The preparation process of the sustained-release microcapsules includes the following steps: S1: Gypsum pretreatment: Weigh the gypsum, grind it, sieve out the gypsum with a particle size of 0.1-0.2μm, add acidic EDTA solution, sonicate at a constant temperature in a water bath at 50-70℃ for 30-45min, filter, dry under reduced pressure, and set aside for later use. S2: Extraction of medicinal liquid: Weigh out mulberry bark, anemarrhena rhizome, bitter almond, and angelica root, grind them into powder and mix them evenly. Put them into an extraction tank, add ethanol for reflux treatment, and after treatment for 2-4 hours, take out the powder and dry it. Then perform ultrasonic cell pulverization, add distilled water for ultrasonic treatment, filter, and concentrate by rotary evaporation. S3: Core material preparation: Weigh the concentrated drug solution obtained in S2, place it in a stoppered conical flask, add the pretreated gypsum from S1, fill with inert gas, seal tightly, stir at 1500-2000 r / min for 30 min, filter, dry under reduced pressure at 30-50℃, and place in a sealed container for later use; S4: Weigh gelatin and aromatic organic acid, add a small amount of deionized water, keep the temperature at 50-60℃, and stir until fully swollen; weigh the core material obtained in S3 and add it to the gelatin solution, stirring to form a suspension as the aqueous phase; mix liquid paraffin and Span to form the oil phase; slowly add the aqueous phase to the oil phase, continue stirring, add isopropanol for dehydration for 3-5 minutes, and cure with glutaraldehyde for 5-10 minutes. Stir, place at 4-6℃ overnight, wash three times with isopropanol and water respectively, filter and dry to obtain the sustained-release microcapsules.

5. The traditional Chinese medicine preparation for clearing heat and relieving cough for livestock and poultry according to claim 4, characterized in that, In S1, the acidic EDTA is prepared by mixing 1.5-2.5mM hydrochloric acid solution and EDTA at a mixing ratio of 3.5-4ml:1mg; the mixing ratio of gypsum and acidic EDTA is 1g:20-25ml.

6. The traditional Chinese medicine preparation for clearing heat and relieving cough for livestock and poultry according to claim 4, characterized in that, In S2, the ultrasonic power is 800-1000W, and the ultrasonic treatment lasts for 30-45 minutes; the mass ratio of the powder to distilled water is 1:20-30.

7. The traditional Chinese medicine preparation for clearing heat and relieving cough for livestock and poultry according to claim 4, characterized in that, In S3, the mixing ratio of the concentrated medicinal solution to the pretreated gypsum is 5-10 ml: 1 g.

8. The traditional Chinese medicine preparation for clearing heat and relieving cough for livestock and poultry according to claim 4, characterized in that, In S4, the mass concentration of gelatin in the gelatin solution is 10-20%; the concentration of Span in liquid paraffin is 1.5-2.0%.

9. The traditional Chinese medicine preparation for clearing heat and relieving cough for livestock and poultry according to claim 4, characterized in that, In S4, the mixing ratio of the core material to the gelatin solution is 1g:50-100ml; the volume of the liquid paraffin used is 0.5-0.7 times that of the gelatin solution.

10. The method for preparing the traditional Chinese medicine preparation for clearing heat and relieving cough for livestock and poultry according to any one of claims 1-9, characterized in that, The process includes the following steps: mixing the prepared sustained-release microcapsules with the suspension mother liquor at a volume ratio of 2-5:10-18 at room temperature to obtain the traditional Chinese medicine preparation.

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