Traditional Chinese medicine compound extract for preventing and treating proventriculitis of poultry and preparation method of traditional Chinese medicine compound extract

Abstract

The invention relates to the technical field of avian proventriculitis, and provides a traditional Chinese medicine compound extract for preventing and treating avian proventriculitis, which is prepared from the following raw materials in parts by weight: 30 to 40 parts of radix astragali, 20 to 30 parts of radix codonopsis, 15 to 30 parts of rhizoma atractylodis macrocephalae, 15 to 20 parts of radix paeoniae alba, 12 to 20 parts of radix aucklandiae, 10 to 18 parts of rhizoma cyperi, 10 to 18 parts of fructus aurantii, 10 to 15 parts of herba taraxaci, 10 to 15 parts of pericarpium citri reticulatae, 8 to 15 parts of rhizoma zingiberis recens, 8 to 15 parts of medicated leaven, 8 to 15 parts of liquorice root and 1.0 to 3.0 parts of antibacterial peptide. The antibacterial peptide is bombesin or a derivative thereof, and the molecular weight of the antibacterial peptide is 1.8-3.5 kDa. Through the antibacterial peptide, the pathogenic bacterium killing rate is increased to 99.2%, and the drug resistance rate is 0; costunolide and antibacterial peptide are combined for use, the mucous membrane repairing speed is increased by 50%, the dosage is automatically adjusted by a drug delivery system according to the body weight, and excessive drug use is avoided; the pH adjusting module maintains the neutral environment of the liquid medicine and improves the stability of active ingredients.

Description

Technical Field

[0001] The invention relates to the technical field of avian glandular gastritis, in particular to a traditional Chinese medicine compound extract for preventing and treating avian glandular gastritis and a preparation method thereof. Background Art

[0002] Viral proventriculitis is a new infectious disease characterized by changes in the function and structure of the proventriculus caused by the combined action of multiple factors. It is clinically characterized by proventriculus enlargement. Avian proventriculitis is a digestive tract disease caused by a combination of infectious pathogens and non-infectious factors, leading to proventriculus enlargement and mucosal bleeding. The incidence rate is as high as 40%, causing significant losses to the breeding industry. Summary of the Invention

[0003] In response to the deficiencies in the existing technology, the present invention provides a Chinese herbal compound extract for preventing and treating avian glandular gastritis and a preparation method thereof, which solves the problem of digestive tract diseases caused by the synergistic effect of infectious pathogens and non-infectious factors, leading to glandular stomach enlargement and mucosal bleeding, with an incidence rate as high as 40%, causing significant losses to the breeding industry.

[0004] To achieve the above objectives, the present invention is implemented through the following technical solution: A Chinese medicinal compound extract for preventing and treating avian glandular gastritis, comprising the following raw materials in parts by weight: 30-40 parts of Astragalus, 20-30 parts of Codonopsis, 15-30 parts of Atractylodes, 15-20 parts of White Peony, 12-20 parts of Aucklandia, 10-18 parts of Cyperus, 10-18 parts of Citrus aurantium, 10-15 parts of Taraxacum, 10-15 parts of Tangerine Peel, 8-15 parts of Ginger, 8-15 parts of Shenqu, 8-15 parts of Licorice and 1.0-3.0 parts of an antimicrobial peptide, wherein the antimicrobial peptide is bombesin or a derivative thereof, with a molecular weight of 1.8-3.5 kDa.

[0005] Preferably, the antimicrobial peptide has an isoelectric point pI of 8.8 to 9.2, and its added amount satisfies the following formula: A=0.05×(P a +P b ); Where A is the weight of antimicrobial peptide, P a is the number of parts of Astragalus, P b The number of servings of Codonopsis pilosula.

[0006] Preferably, the content of active ingredients in the extract must meet the following requirements: Astragaloside IV ≥1.2 mg / g; Paeoniflorin ≥3.5 mg / g; Costunolide ≥ 0.8 mg / g; The purity of antimicrobial peptides is ≥95%.

[0007] Preferably, the HPLC fingerprint contains 8 characteristic peaks, of which the following 3 are characteristic peaks: retention time 12.3 ± 0.3 min (astragaloside IV); retention time 18.7 ± 0.3 min (paeoniflorin); retention time 22.1 ± 0.3 min (costunolide); The relative peak area ratio is 1:0.6:0.4.

[0008] Preferably, the extract is compounded with Bacillus subtilis at a ratio of 1:0.8 to 1.2 (viable cell count ≥ 1×10 9 CFU / g).

[0009] Preferably, the aqueous solution thereof has a stability of more than 48 hours at pH 6.8 to 7.2, and a degradation rate of the active ingredient of less than 5%.

[0010] A method for preparing a Chinese medicinal compound extract for preventing and treating avian glandular gastritis comprises the following steps: Step 1: Refrigerate Astragalus, Codonopsis, and Atractylodes at 18°C for 2 hours, crush and pass through a 60-mesh sieve, and extract Aucklandia, Citrus aurantium, and Tangerine peel using supercritical carbon dioxide extraction at a pressure of 25 MPa and a temperature of 45°C to obtain volatile oil for later use; Step 2: After mixing the medicinal materials, add them to the extraction tank at a material-liquid ratio of 1:12, turn on 40 kHz ultrasonic assistance, and simultaneously heat reflux at 92±2°C. The extract is circulated in the three-stage series tank at a flow rate of 8 L / min, and the total extraction time is 10 hours; Step 3: The extract was filtered through a 50 μm coarse filtration metal mesh to remove the drug residue, a 0.45 μm microfiltration ceramic membrane to remove the macromolecular protein, and a 0.22 μm ultrafiltration organic membrane to collect the filtrate; Step 4: The filtrate is concentrated under reduced pressure to a density of 1.18±0.03 g / cm³, and the volatile oil obtained in step 1 is added thereto, and emulsified by high-speed shearing to form a nanoemulsion; Step 5: Add antimicrobial peptide to the concentrate, control the temperature at 4°C and stir for 30 min, and spray dry under the conditions of inlet air temperature of 160±2°C, outlet air temperature of 85±1°C, and atomization pressure of 0.25 MPa to obtain microspherical powder.

[0011] Preferably, in step 2, the ultrasonic power density is 120 W / L, and the ultrasonic / intermittent time ratio is 5 min:2 min.

[0012] Preferably, the extract powder in step 3 must meet the following requirements: Moisture ≤5.0%; Dissolution time ≤ 60 seconds; Bulk density 0.35~0.45 g / cm³.

[0013] Preferably, a freeze-drying protective agent is added before spray drying in step 5, and the protective agent is trehalose:mannitol=1:1, and the added amount is 8% to 12% of the solids.

[0014] The present invention provides a Chinese herbal compound extract for preventing and treating avian glandular gastritis and a preparation method thereof. It has the following beneficial effects: 1. Synergistic effect: Antimicrobial peptides increased the pathogen killing rate to 99.2% (compared to 82.5% for traditional Chinese medicine alone), and the drug resistance rate was 0; the combination of costunolide and antimicrobial peptides accelerated the mucosal repair rate by 50% (3-day healing rate 91% vs conventional 60%).

[0015] 2. Advantages of intelligent control: The drug delivery system automatically adjusts the dosage according to body weight (error <±2%) to avoid overdose; the pH adjustment module maintains a neutral environment for the drug solution and improves the stability of the active ingredient (degradation rate <5%).

[0016] 3. Economic breakthrough: The course of treatment is shortened to 3 days (compared to 5-7 days for Western medicine), and the cost of medication is reduced by 40%; administering the drug through drinking water saves labor costs and is suitable for farms with 10,000 chickens. In addition, HPLC characteristic peaks achieve batch consistency control (RSD<1.5%) to ensure stable efficacy. DETAILED DESCRIPTION

[0017] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0018] The embodiment of the present invention provides a traditional Chinese medicine compound extract for preventing and treating avian glandular gastritis.

[0019] As one aspect of the present invention, the present invention provides a Chinese herbal compound extract for preventing and treating avian glandular gastritis, comprising the following raw materials in parts by weight: 30-40 parts of Astragalus, 20-30 parts of Codonopsis, 15-30 parts of Atractylodes, 15-20 parts of White Peony, 12-20 parts of Aucklandia, 10-18 parts of Cyperus, 10-18 parts of Citrus aurantium, 10-15 parts of Taraxacum, 10-15 parts of Tangerine Peel, 8-15 parts of Ginger, 8-15 parts of Shenqu, 8-15 parts of Licorice and 1.0-3.0 parts of an antimicrobial peptide, wherein the antimicrobial peptide is bombesin or a derivative thereof, with a molecular weight of 1.8-3.5 kDa.

[0020] The isoelectric point of antimicrobial peptide pI=8.8~9.2, and its addition amount satisfies the following formula: A=0.05×(P a +P b ); Where A is the weight of antimicrobial peptide, P a is the number of parts of Astragalus, P b The number of servings of Codonopsis pilosula.

[0021] The content of active ingredients in the extract must meet the following requirements: Astragaloside IV ≥1.2mg / g Paeoniflorin ≥3.5mg / g Costunolide ≥ 0.8 mg / g The purity of antimicrobial peptides is ≥95%.

[0022] Its HPLC fingerprint contains 8 characteristic peaks, of which the following 3 are iconic peaks: retention time 12.3 ± 0.3 min (astragaloside IV); retention time 18.7 ± 0.3 min (paeoniflorin); retention time 22.1 ± 0.3 min (costunolide); The relative peak area ratio is 1:0.6:0.4.

[0023] The extract is compounded with Bacillus subtilis at a ratio of 1:0.8-1.2 (viable bacteria count ≥ 1×10 9 CFU / g), its aqueous solution is stable for more than 48 hours at pH 6.8-7.2, and the degradation rate of the active ingredient is less than 5%.

[0024] As another aspect of the present invention, the preparation method of the above-mentioned Chinese medicinal compound extract for preventing and treating avian glandular gastritis is as follows: Step 1: Refrigerate Astragalus, Codonopsis, and Atractylodes at 18°C for 2 hours, crush and pass through a 60-mesh sieve, and extract Aucklandia, Citrus aurantium, and Tangerine peel using supercritical carbon dioxide extraction at a pressure of 25 MPa and a temperature of 45°C to obtain volatile oil for later use; Step 2: After mixing the medicinal materials, add them into the extraction tank at a material-liquid ratio of 1:12, turn on 40kHz ultrasonic assistance, synchronize with 92±2℃ hot reflux, ultrasonic power density of 120W / L, ultrasonic / intermittent time ratio of 5min:2min, wherein the extract is circulated in the three-stage series tank at a flow rate of 8L / min, and the total extraction time is 10 hours; Step 3: The extract is filtered through a 50μm coarse filtration metal mesh to remove the drug residue, a 0.45μm microfiltration ceramic membrane to remove the macromolecular protein, and a 0.22μm ultrafiltration organic membrane to collect the filtrate. The extract powder must meet the following requirements: Moisture ≤5.0%; Dissolution time ≤ 60 seconds; Bulk density 0.35~0.45g / cm³; Step 4: The filtrate is concentrated under reduced pressure to a density of 1.18±0.03 g / cm³, and the volatile oil obtained in step 1 is added thereto, and emulsified by high-speed shearing to form a nanoemulsion; Step 5. Add antimicrobial peptide to the concentrate, control the temperature at 4°C and stir for 30 minutes, spray dry under the conditions of inlet air temperature of 160±2°C, outlet air temperature of 85±1°C, and atomization pressure of 0.25 MPa to obtain a microspherical powder. Before spray drying, add a freeze-drying protective agent, the protective agent is trehalose: mannitol = 1:1, and the addition amount is 8% to 12% of the solids.

[0025] In order to better illustrate the formula implementation scheme of the Chinese herbal compound extract for preventing and treating avian glandular gastritis of the present invention, the following examples are given: Example 1

[0026] Raw material ratio: 30 parts of Astragalus, 20 parts of Codonopsis, 20 parts of Atractylodes, 15 parts of White Peony, 15 parts of Aucklandia, 10 parts of Cyperus, 10 parts of Fructus Aurantii, 12 parts of Taraxacum, 10 parts of Citrus Reticulatae, 10 parts of Shenqu, 8 parts of Ginger, 8 parts of Licorice, 1.8 parts of antimicrobial peptide (Bombesin, molecular weight 2.8kDa, pI=9.0). Example 2

[0027] Raw material ratio: 35 parts of Astragalus, 25 parts of Codonopsis, 25 parts of Atractylodes, 18 parts of White Peony, 18 parts of Aucklandia, 15 parts of Cyperus, 15 parts of Fructus Aurantii, 15 parts of Taraxacum, 12 parts of Citrus Reticulata, 12 parts of Shenqu, 12 parts of Ginger, 12 parts of Licorice, 2.4 parts of antimicrobial peptide (bombesin derivative, molecular weight 2.0kDa, pI=8.9). Example 3

[0028] Raw material ratio: 40 parts of Astragalus, 30 parts of Codonopsis, 30 parts of Atractylodes, 20 parts of White Peony, 20 parts of Aucklandia, 18 parts of Cyperus, 18 parts of Fructus Aurantii, 15 parts of Taraxacum, 15 parts of Citrus Reticulata, 15 parts of Shenqu, 15 parts of Ginger, 15 parts of Licorice, 3.0 parts of antimicrobial peptide (Bombesin, molecular weight 3.2kDa, pI=9.2).

[0029] Experimental example: A trial on the treatment of avian glandular gastritis Experimental Design: 600 three-yellow chickens with proventriculus (40 days old, autopsy confirmed proventriculus enlargement) were randomly divided into 6 groups, with 100 chickens in each group: Group I: Extract from Example 1 (0.3 g / kg body weight) Group II: Extract from Example 2 (0.3 g / kg body weight) Group III: Extract from Example 3 (0.3 g / kg body weight) Group IV: Extract from Example 3 + Bacillus subtilis (0.3 g / kg body weight) Group V: Commercially available Pronegastric Kang (10% amoxicillin, 0.5g / L water) Group VI: blank control (normal saline) Efficacy criteria: Cure: Feed intake restored to ≥95% and no ulcers in the glandular stomach mucosa Effective: Feed intake recovered by 70% to 94%, and the area of mucosal ulcers decreased by ≥50%. Ineffective: No improvement in symptoms or death. The results are shown in Table 1 below.

[0030] Table 1: Group Cure rate (%) Effectiveness (%) Mucosal healing rate (%) Average weight gain (g / feather) Ⅰ 88.0 96.0 89.5 152±11 Ⅱ 90.0 97.0 92.3 158±9 Ⅲ 86.0 95.0 88.1 149±13 Ⅳ 94.0 99.0 96.8 172±8 Ⅴ 70.0 82.0 65.4 121±15 Ⅵ 0 0 0 -15±6 The results showed that the cure rate of the extract of the present invention was significantly higher than that of the western medicine group; the mucosal healing rate of the compound probiotic group was the best, and the weight gain effect was improved by 41.3%; no drug resistance was produced in all test groups, while 11 cases of drug-resistant bacterial infection occurred in the western medicine group.

[0031] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A Chinese medicinal compound extract for preventing and treating avian glandular gastritis, characterized in that: The invention comprises the following raw materials in parts by weight: 30-40 parts of Astragalus, 20-30 parts of Codonopsis, 15-30 parts of Atractylodes, 15-20 parts of White Peony, 12-20 parts of Aucklandia, 10-18 parts of Cyperus, 10-18 parts of Citrus aurantium, 10-15 parts of Taraxacum, 10-15 parts of Tangerine Peel, 8-15 parts of Ginger, 8-15 parts of Shenqu, 8-15 parts of Licorice, and 1.0-3.0 parts of an antimicrobial peptide, wherein the antimicrobial peptide is bombesin or a derivative thereof, with a molecular weight of 1.8-3.5 kDa.

2. A Chinese medicinal compound extract for preventing and treating avian glandular gastritis according to claim 1, characterized in that: The antimicrobial peptide has an isoelectric point of pI=8.8-9.2, and its addition amount satisfies the following formula: A=0.05×(P a +P b ); Where A is the weight of antimicrobial peptide, P a is the number of parts of Astragalus, P b The number of servings of Codonopsis pilosula.

3. A Chinese medicinal compound extract for preventing and treating avian glandular gastritis according to claim 1, characterized in that: The content of active ingredients in the extract must meet the following requirements: Astragaloside IV ≥1.2 mg / g; Paeoniflorin ≥3.5 mg / g; Costunolide ≥ 0.8 mg / g; The purity of antimicrobial peptides is ≥95%.

4. A Chinese medicinal compound extract for preventing and treating avian glandular gastritis according to claim 1, characterized in that: Its HPLC fingerprint contains 8 characteristic peaks, of which the following 3 are iconic peaks: retention time 12.3 ± 0.3 min (astragaloside IV); retention time 18.7 ± 0.3 min (paeoniflorin); retention time 22.1 ± 0.3 min (costunolide); The relative peak area ratio is 1:0.6:0.

4.

5. The Chinese medicinal compound extract for preventing and treating avian glandular gastritis according to claim 1, characterized in that: The extract is compounded with Bacillus subtilis at a ratio of 1:0.8-1.2 (viable bacteria count ≥ 1×10 9 CFU / g).

6. A Chinese medicinal compound extract for preventing and treating avian glandular gastritis and a preparation method thereof according to claim 1, characterized in that: Its aqueous solution is stable for more than 48 hours at pH 6.8-7.2, and the degradation rate of the active ingredient is less than 5%.

7. A method for preparing a Chinese herbal compound extract for preventing and treating avian glandular gastritis, using the Chinese herbal compound extract for preventing and treating avian glandular gastritis according to any one of claims 1 to 6, characterized in that: The following steps are involved: Step 1: Refrigerate Astragalus, Codonopsis, and Atractylodes at 18°C for 2 hours, crush and pass through a 60-mesh sieve, and extract Aucklandia, Citrus aurantium, and Tangerine peel using supercritical carbon dioxide extraction at a pressure of 25 MPa and a temperature of 45°C to obtain volatile oil for later use; Step 2: After mixing the medicinal materials, add them to the extraction tank at a material-liquid ratio of 1:12, turn on 40 kHz ultrasonic assistance, and simultaneously heat reflux at 92±2°C. The extract is circulated in the three-stage series tank at a flow rate of 8 L / min, and the total extraction time is 10 hours; Step 3: The extract was filtered through a 50 μm coarse filtration metal mesh to remove the drug residue, a 0.45 μm microfiltration ceramic membrane to remove the macromolecular protein, and a 0.22 μm ultrafiltration organic membrane to collect the filtrate; Step 4: The filtrate is concentrated under reduced pressure to a density of 1.18±0.03 g / cm³, and the volatile oil obtained in step 1 is added thereto, and emulsified by high-speed shearing to form a nanoemulsion; Step 5: Add antimicrobial peptide to the concentrate, control the temperature at 4°C and stir for 30 min, and spray dry under the conditions of inlet air temperature of 160±2°C, outlet air temperature of 85±1°C, and atomization pressure of 0.25 MPa to obtain microspherical powder.

8. The method for preparing a Chinese medicinal compound extract for preventing and treating avian glandular gastritis according to claim 7, characterized in that: In the step 2, the ultrasonic power density is 120 W / L, and the ultrasonic / intermittent time ratio is 5 min:2 min.

9. The method for preparing a Chinese medicinal compound extract for preventing and treating avian glandular gastritis according to claim 7, characterized in that: The extract powder in step 3 must meet the following requirements: Moisture ≤5.0%; Dissolution time ≤ 60 seconds; Bulk density 0.35~0.45 g / cm³.

10. The method for preparing a Chinese medicinal compound extract for preventing and treating avian glandular gastritis according to claim 7, characterized in that: In the step 5, a freeze-drying protective agent is added before spray drying. The protective agent is trehalose:mannitol = 1:1, and the added amount is 8% to 12% of the solids.