CN113040279A - Antibacterial detoxified feed additive and feed containing the same - Google Patents
Antibacterial detoxified feed additive and feed containing the same Download PDFInfo
- Publication number
- CN113040279A CN113040279A CN202110441999.3A CN202110441999A CN113040279A CN 113040279 A CN113040279 A CN 113040279A CN 202110441999 A CN202110441999 A CN 202110441999A CN 113040279 A CN113040279 A CN 113040279A
- Authority
- CN
- China
- Prior art keywords
- andrographolide
- montmorillonite
- modified montmorillonite
- antibacterial
- feed additive
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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Abstract
The invention provides an antibacterial detoxified feed additive, which comprises: the andrographolide modified montmorillonite mainly comprises polyethylene glycol composite modified montmorillonite and andrographolide, and the andrographolide is adsorbed or intercalated in a crystal structure of the PEG composite modified montmorillonite. Therefore, the antibacterial and detoxified feed additive can simultaneously have the advantages of montmorillonite and andrographolide, can adsorb mycotoxin, reduce mycotoxins such as aflatoxin B1 and zearalenone in the feed, and is used as a mycotoxin detoxifier; can also adsorb microorganisms such as Escherichia coli, has antibacterial and bactericidal effects, and can replace feed antibiotics. The invention also provides a feed containing the antibacterial and detoxified feed additive, and the addition amount of the antibacterial and detoxified feed additive is less than or equal to 1 percent. The feed can realize feed detoxification, prevent animal mycotoxin poisoning and prevent livestock diarrhea; and has the characteristics of safe storage and use, low feeding cost and the like.
Description
Technical Field
The invention belongs to the field of feed, and particularly relates to an antibacterial and detoxified feed additive and feed containing the same.
Background
The prevention and treatment of animal epidemic diseases and the mycotoxin pollution of the feed are two major problems facing the healthy breeding, although the antibiotics added in the feed have the advantages of resisting bacteria, protecting health, improving the survival rate, promoting growth, improving the feed conversion efficiency and the like, in recent years, the abuse of the antibiotics can bring serious consequences such as drug-resistant bacteria, teratogenesis, carcinogenesis and the like. From 7 months and 1 day in 2020, feed production enterprises in China stop producing commercial feeds containing growth-promoting drug feed additives (except traditional Chinese medicines). Therefore, the development of antibiotic substitutes is urgent.
At present, the proportion of mycotoxin appearing in feed grains all over the world is up to more than 25%, according to the survey of feed samples in 2019, the pollution of corn and byproducts, namely aflatoxin B1 and zearalenone, is the most serious, and the overproof rates respectively reach 12.0% and 1.1%; the cake meal raw material is obviously polluted by aflatoxin B1, the overproof rate is 11.8%, and the pollution degree is only second to that of corn and byproducts thereof (12.0%); the bran sample has moderate pollution of vomitoxin, the DDGS sample is mainly polluted by aflatoxin B1, the overproof rate reaches 10.0%, and the DDGS sample is moderately polluted by vomitoxin (66.7%). In addition to causing significant economic losses to the animal husbandry industry, some mycotoxins are carcinogenic or teratogenic and can be transmitted to human beings through meat and milk consumption, and the research and development of mycotoxin detoxifiers are always the key point of the livestock breeding industry.
Currently, research on antibiotic substitutes mainly focuses on biological feed additives, plant extracts and the like, and the elimination of mycotoxins mainly adopts biodegradation or physical adsorption technology. In the prior art, biological feed additives or plant extracts which can replace antibiotics and can eliminate mycotoxins are rarely reported.
Disclosure of Invention
In view of the above, the present invention provides an antibiotic detoxified feed additive and a feed containing the same, wherein the antibiotic detoxified feed additive can replace antibiotics to prevent diarrhea of livestock and poultry, and can adsorb mycotoxin to detoxify the feed and prevent mycotoxin poisoning of animals.
Therefore, the antibacterial and detoxified feed additive provided by the invention comprises andrographolide modified montmorillonite which mainly comprises polyethylene glycol (PEG) composite modified montmorillonite and andrographolide, and the andrographolide is adsorbed or intercalated in the crystal structure of the PEG composite modified montmorillonite. Specifically, andrographolide is adsorbed or intercalated between layers of the PEG composite modified montmorillonite crystal structure, and part of cations on the montmorillonite crystal structure are replaced.
Preferably, in the andrographolide modified montmorillonite, the adsorption capacity of andrographolide is 1.80-10.33 mg/g. More preferably, the adsorption capacity of the andrographolide on the andrographolide modified montmorillonite is 5.00-10.33 mg/g.
The andrographolide modified montmorillonite is mainly prepared by the following method: mixing andrographolide and PEG composite modified montmorillonite in water, reacting at constant temperature and at a stirring speed of 80-200 r/min, and then centrifuging, washing and drying to obtain the andrographolide modified montmorillonite.
Wherein, the andrographolide can be purchased directly from the market or made by the user; preferably, andrographolide is extracted from the extract of Andrographis paniculata Nees by sonication with an organic solvent.
When the andrographolide is prepared by self, the andrographolide modified montmorillonite is mainly prepared by the following method: firstly, placing the andrographis paniculata extract in an ethanol solution with the volume fraction of more than or equal to 60 percent for ultrasonic extraction treatment, and adding water and the PEG composite modified montmorillonite; stirring and reacting for 0.5-4 h under the conditions that the reaction pH value is 5-11 and the reaction temperature is 40-80 ℃; and then centrifuging, washing and drying to obtain the andrographolide modified montmorillonite. Wherein the substance for adjusting pH value is alkaline substance such as sodium hydroxide and potassium hydroxide. Preferably, the mass ratio of the PEG composite modified montmorillonite to the andrographis paniculata extract is 2: 1-10: 1. The pH value is preferably 8 to 11.
Wherein the PEG composite modified montmorillonite comprises metal ionized montmorillonite and PEG, and the PEG is intercalated between layers of the crystal structure of the metal ionized montmorillonite; preferably, the PEG is polyethylene glycol 1000. The PEG composite modified montmorillonite is mainly prepared by the following method: dispersing metal ionized montmorillonite in water in a water bath, adding PEG, stirring for reaction, and then centrifuging, washing, drying, grinding and sieving to obtain the PEG composite modified montmorillonite.
The metal-ionized montmorillonite is sodium-modified montmorillonite or potassium-modified montmorillonite, and is mainly prepared by the following steps: mixing raw ore montmorillonite powder with water to prepare ore pulp, adding a soluble carbonate solution, stirring and reacting under a constant temperature condition, and then centrifuging, washing, drying, grinding and sieving to prepare the metal ionized montmorillonite; wherein the soluble carbonate solution comprises sodium carbonate solution, potassium carbonate solution, sodium bicarbonate solution or potassium carbonate hydrogen solution.
The invention also provides a feed which comprises the antibacterial and detoxified feed additive, and the addition amount of the antibacterial and detoxified feed additive is less than or equal to 1%. Preferably, the addition amount of the antibacterial and detoxified feed additive is between 0.2 and 1 percent.
The feed also includes an animal basal ration. The basic ration for animals can be basic ration for pig, chicken, duck, rabbit, cattle, horse, dog, etc. in each growth stage. Preferably, the basic ration of the animal basic ration comprises the following components in percentage by mass: 15 to 22 percent of crude protein, 5 to 8 percent of crude fat, less than 3 percent of crude ash, 0.8 to 2 percent of lysine, 0.5 to 0.8 percent of sodium chloride, 0.4 to 0.7 percent of phosphorus and 0.7 to 1 percent of calcium.
The antibacterial and detoxified feed additive provided by the invention comprises andrographolide modified montmorillonite which mainly comprises polyethylene glycol (PEG) composite modified montmorillonite and andrographolide, wherein andrographolide is adsorbed or intercalated between layers of a crystal structure of the PEG composite modified montmorillonite and also replaces cations in crystal lattices of the PEG composite modified montmorillonite to form a stable andrographolide montmorillonite compound. Therefore, the antibacterial and detoxified feed additive can simultaneously have the advantages of montmorillonite and andrographolide, can adsorb mycotoxin, reduce mycotoxins such as aflatoxin B1 and zearalenone in feed, and is used as a mycotoxin detoxifier; can also adsorb microorganisms such as Escherichia coli, has antibacterial and bactericidal effects, and can replace feed antibiotics. Therefore, the antibacterial and detoxified feed additive and the feed containing the additive can realize feed detoxification, prevent animal mycotoxin poisoning and prevent livestock diarrhea. In addition, the antibacterial and detoxified feed additive can be stored for a long time under the condition of drying at room temperature, the addition amount of the additive in the feed is less than or equal to 1 percent, and the feed additive has the characteristics of safe storage and use, low feeding cost and the like.
Drawings
FIG. 1 is a scanning electron microscope image of PEG composite modified montmorillonite.
FIG. 2 is a scanning electron microscope image of andrographolide-modified montmorillonite.
FIG. 3 is an infrared spectrum of andrographolide modified montmorillonite.
FIG. 4 is an infrared spectrum of PEG-modified montmorillonite.
FIG. 5 is a thermogravimetric analysis map of andrographolide-modified montmorillonite.
FIG. 6 is a bar graph showing the adsorption rate of various types of montmorillonite to Escherichia coli.
FIG. 7 is a graph showing the effect of the concentration of andrographolide-modified montmorillonite on the bacterial leakage rate of Escherichia coli.
FIG. 8 is a graph showing the effect of the concentration of andrographolide-modified montmorillonite on the conductivity of E.coli culture.
FIG. 9 is a graph showing the adsorption effect of andrographolide-modified montmorillonite on aflatoxin B1.
FIG. 10 is a graph showing the adsorption effect of andrographolide-modified montmorillonite on zearalenone.
Detailed Description
The technical solution of the present invention is further described in detail by the following embodiments. Unless otherwise specified, the technical means used in the following examples are conventional means well known to those skilled in the art.
Wherein, the raw montmorillonite ore in the montmorillonite materials used in the following examples is from Nemontage-Haoyang, andrographolide is from Shanghai Homophor Biotech GmbH, Andrographis paniculata extract is from Guilin Sparganium Biotech, Enterotoxin-producing Escherichia coli (E.coli) ((C.))Escherichia coli ETEC Strain number CICC 10667) was purchased from china collection of microorganisms management center.
Example 1
The embodiment provides an antibacterial and detoxified feed additive which consists of andrographolide modified montmorillonite, wherein the andrographolide modified montmorillonite mainly consists of polyethylene glycol 1000 modified montmorillonite and andrographolide, and the andrographolide is adsorbed or intercalated between layers of a crystal structure of the polyethylene glycol 1000 modified montmorillonite and simultaneously replaces cations on the crystal structure of the montmorillonite; in the andrographolide-modified montmorillonite, the adsorption capacity of andrographolide is 10.33 mg/g. The "adsorption amount of andrographolide" herein mainly refers to a ratio of the mass of andrographolide adsorbed or intercalated in the crystal structure of the PEG composite modified montmorillonite to the mass of the PEG composite modified montmorillonite.
The antibacterial and detoxified feed additive provided by the embodiment of the invention is mainly prepared by the following method:
na modification treatment, namely preparing raw ore montmorillonite powder and water into ore pulp according to the mass ratio of 1:8, and adding 4.0 mass percent of Na2CO3Stirring the solution for 2 h in a constant-temperature water bath kettle at 80 ℃, then washing the solution for multiple times by using a centrifugal machine, drying the product for 6 h at 80 ℃, and grinding and sieving the product by using a 200-mesh sieve to obtain Na-montmorillonite;
performing PEG modification treatment, namely taking 10 g of prepared Na-montmorillonite, dispersing in 80 mL of distilled water in a water bath at 60 ℃ for 2 h, then adding 0.4 g of polyethylene glycol 1000, continuously stirring for 1.5 h, adding a proper amount of absolute ethyl alcohol, performing centrifugal washing by using distilled water, performing multiple washing, drying at 60 ℃ for 10 h, grinding and sieving to obtain PEG composite modified montmorillonite, wherein a scanning electron microscope photo of the PEG composite modified montmorillonite is shown in figure 1;
treating andrographolide modified montmorillonite by ultrasonically extracting 0.200 g of andrographis paniculata extract by using 75% ethanol solution with volume fraction for 20 min, adding 20 mL of distilled water, weighing 0.500 g of PEG composite modified montmorillonite, and reacting in a constant-temperature water bath oscillator under the conditions of 120 r/min, adjusting the pH value to 10 by using sodium hydroxide, adjusting the reaction temperature to 60 ℃ and reacting for 2 h to obtain a reaction product; centrifuging the reaction product in a centrifuge at 4000 r/min for 10 min, washing for three times, collecting bottom precipitate, and freeze-drying under vacuum to obtain andrographolide modified montmorillonite, wherein scanning electron microscope photograph of the andrographolide modified montmorillonite is shown in FIG. 2.
Comparing fig. 1 and fig. 2, it is found that: although the surface morphology of the PEG composite modified montmorillonite and the andrographolide modified montmorillonite is changed, the basic crystal form skeleton of the PEG composite modified montmorillonite and the andrographolide modified montmorillonite is not changed. In fig. 2 it is shown that andrographolide modified montmorillonite has some spheroidal particles, which may be caused by the increased hydrophobicity between montmorillonite mineral layers due to the addition of andrographolide, resulting in a change in the cohesion between montmorillonite layers, thus demonstrating the insertion of andrographolide between the layers of montmorillonite crystal structure.
1. Structural characterization of the antibacterial detoxified feed additive provided in this example
By separately comparing the antibacterial detoxified feed additive provided in the examples: the andrographolide modified montmorillonite and the PEG composite modified montmorillonite adopted in the embodiment are subjected to Fourier transform infrared spectroscopy for scanning analysis, and the structure of the andrographolide modified montmorillonite provided in the embodiment is represented by comparison analysis of an infrared spectrogram.
Comparing fig. 3 and fig. 4, it can be seen that: the andrographolide modified montmorillonite and PEG composite modified montmorillonite are 2789, 1727, 1453 and 1060cm-1The characteristic absorption peaks appear in the vicinity of the probe, wherein the absorption peak is 2789 cm-1The methylene C-H stretching vibration peak is mainly the characteristic absorption peak of PEG in the PEG composite modified montmorillonite, and is at 1727, 1453 and 1060cm-1The characteristic absorption peak near the position is the main characteristic absorption peak of the montmorillonite mineral, so that the andrographolide modified montmorillonite does not change the basic structure of the montmorillonite, the basic structure of the montmorillonite mineral is completely preserved, and the basic structure of the PEG composite modified montmorillonite is not changed.
In FIG. 3, the andrographis paniculata modified montmorillonite is shown at 3397 cm-1A broader characteristic peak appears, which is the stretching vibration peak of-OH in andrographolide; 1650 cm-1Nearby occurrence of H2The bending vibration peak of O indicates that-OH is replaced; and andrographolide modified montmorillonite at 1727, 1453 and 1060cm-1The characteristic peaks at (A) all appeared to be weakened to various degrees, which is probably caused by that andrographolide is inserted into the interlayer of the montmorillonite crystal structure, so that the Si-O-Si bonds and Si-O bonds between the layers of the montmorillonite crystal structure are weakened. Thereby further proving that andrographolide is inserted into PEG composite modified montmorilloniteThe interlayer of the crystal structure of montmorillonite in the stone is substituted with ion on montmorillonite to form stable andrographis paniculata montmorillonite compound.
2. The heat stability analysis of the antibacterial detoxified feed additive provided in this example
Aiming at the antibacterial and detoxified feed additive provided by the embodiment: the andrographolide modified montmorillonite is subjected to thermogravimetric analysis under the conditions that the temperature range is 40-600 ℃ and the temperature rise rate is 10 ℃/min, and the analysis result is shown in figure 5.
From the thermogravimetric analysis shown in fig. 5, it can be seen that: the thermal gravimetric decomposition of andrographolide modified montmorillonite is roughly divided into three stages: wherein, the evaporation of free water between montmorillonite molecule layers, the thermal decomposition of organic molecules such as PEG and andrographolide, and the removal of montmorillonite silicate sheet hydroxyl.
Before the pyrolysis temperature reaches 200 ℃, the water between molecular layers of the andrographolide modified montmorillonite is evaporated, the quality is rapidly reduced by 3.87%.
The thermal decomposition of the intercalated organic components such as PEG, andrographolide and the like in the molecular structure of the montmorillonite is carried out at the temperature of 200-525 ℃, the quality of the andrographolide modified montmorillonite is reduced by 12.03 percent at the stage, and the quality reduction rate reaches the peak at the temperature of 314 ℃, which is mainly caused by the fact that the thermal stability of the andrographolide is poor and the andrographolide is significantly degraded at the temperature of about 300 ℃. Thus, the andrographolide intercalated PEG composite modified montmorillonite has no significant influence on the thermal stability of andrographolide.
The removal of hydroxyl groups from silicate sheets takes place after 525 ℃ and there is a tendency for the quality to decline slowly at this stage. It can thus be demonstrated that andrographolide is adsorbed into the layers of the montmorillonite crystal structure.
3. The antibacterial performance of the antibacterial and detoxified feed additive provided by the embodiment is verified
(1) Effect of different types of montmorillonite on the adsorption Rate of Escherichia coli
0.100 g of each of five types of montmorillonite powder was accurately weighed in 100 mL of sterilized PBS buffer, and 100. mu.L of montmorillonite powder having a concentration of about 10 was pipetted8Placing the activated bacterial liquid of CFU/mL in a buffer solution, shaking for 2 h at constant temperature of 37 ℃, and taking the supernatantLiquid, coating and counting; respectively calculating the apparent in vitro adsorption rate of the montmorillonite of the different types to the escherichia coli. The results are shown in FIG. 6. Wherein, the five types of montmorillonite powder are respectively as follows: the andrographolide-modified montmorillonite, the polyethylene glycol 1000 composite modified montmorillonite, the sodium-modified montmorillonite, the raw mineral montmorillonite powder and the montmorillonite simple mixed powder provided by the embodiment; the montmorillonite simple mixed powder is prepared by simply and uniformly mixing 10.33 mg of andrographolide and 1 g of polyethylene glycol 1000 composite modified montmorillonite.
The bar graph data in fig. 6 are marked with an x to indicate significant differences (P < 0.05), and the same or no x indicates insignificant differences (P > 0.05). Fig. 6 shows that under the condition that the concentrations of the four types of montmorillonite are all 1 mg/mL, both the Na-modified montmorillonite and the PEG composite modified montmorillonite have a tendency of reducing the adsorption capacity to escherichia coli, and the simple mixed powder of montmorillonite has no influence on the growth of escherichia coli, but the antibacterial detoxification feed additive provided by the embodiment can significantly improve the apparent adsorption rate of montmorillonite to bacteria by utilizing andrographolide modification; on the one hand, the interlayer spacing is increased, the positive charge content is higher and the adsorption capacity to bacteria is enhanced probably because the montmorillonite crystals in the andrographolide modified montmorillonite layer material are increased; on the other hand, it is probably because andrographolide itself has the effects of destroying the surface morphology of bacteria and damaging the structure of bacteria, which promotes the destruction of bacterial cell membrane, and leakage of intracellular protein and intracellular ion, resulting in bacterial death.
(2) Antibacterial test of andrographolide modified montmorillonite
Inoculating escherichia coli in an andrographolide modified montmorillonite culture medium with the concentration of 0-200 mg/mL, culturing in a constant-temperature shaking table at 37 ℃, sampling at 2, 4, 6 and 8 hours respectively, centrifuging at 5000 r/min for 5 min, and taking a supernatant to measure the total leakage rate of escherichia coli and the conductivity of a culture solution. The measurement results are shown in fig. 7 and 8, respectively.
As can be seen in fig. 7 and 8: the andrographolide modified montmorillonite can improve the bacterial leakage rate of Escherichia coli and the conductivity of culture solution, and can increase with the increase of the dose of andrographolide modified montmorillonite. Andrographolide at 200 mg/mLThe modified montmorillonite can remarkably improve the bacterial leakage rate and the conductivity (P) in 6 th and 8 th hours<0.05), it can be thus demonstrated that: 200 mg/mL andrographolide modified montmorillonite can significantly improve thallus cracking of Escherichia coli, and thallus intracellular charge Na+、K+The plasma dissolves out, resulting in the increase of the conductivity of the bacteria culture solution. Therefore, the PEG composite modified montmorillonite is used as a carrier of andrographolide, and andrographolide is slowly released in a culture solution, so that the andrographolide modified montmorillonite can inhibit escherichia coli and has the functions of bacteriostasis and sterilization.
4. Mycotoxin detoxification test of antibacterial detoxified feed additive provided in this example
The experiment is mainly carried out by modifying montmorillonite with andrographolide to aflatoxin B1 (AFB)1) And the adsorption effect of Zearalenone (ZEN) to reflect the detoxification effect of the andrographolide modified montmorillonite.
Wherein, the sodium montmorillonite, the PEG composite modified montmorillonite and the andrographis paniculata modified montmorillonite are respectively added into the sprayed corn bran according to the mass ratio of 0.1%, 0.2%, 0.3%, 0.4%, 0.5% and 1%, the mixture is evenly mixed and placed for 24 h, and the ZEN and AFB in the sample are measured1The content of (a). The test results are shown in fig. 9 and 10.
As can be seen in fig. 9 and 10: three montmorillonite pairs AFB1And ZEN have adsorption effect, and the adsorption effect is enhanced along with the increase of the addition amount of the andrographis paniculata modified montmorillonite. However, andrographolide-modified montmorillonite has the best adsorption effect, and when the amount of andrographolide-modified montmorillonite is 1%, the adsorption effect on AFB is good1And ZEN adsorption rates of 62.60% and 43.38%, respectively.
Example 2
The antibacterial and detoxified feed additive comprises andrographolide modified montmorillonite, the structural composition of which is basically the same as that of the andrographolide modified montmorillonite provided in example 1, and the main difference is that: in the andrographolide-modified montmorillonite of this example, the adsorption amount of andrographolide was 9.33 mg/g.
The preparation method of andrographolide-modified montmorillonite provided in this example is basically the same as the preparation method provided in example 1, and the main difference is that:
treating andrographolide modified montmorillonite 0.1 g of andrographis paniculata extract is extracted by adopting 75% ethanol solution with volume fraction for 20 min by ultrasonic wave, 20 mL of distilled water is added, 0.250 g of PEG composite modified montmorillonite is weighed, and the reaction conditions in a constant temperature water bath oscillator under the condition of default pH value of a reaction system are as follows: 120 r/min, the reaction temperature is 60 ℃, and the reaction time is 2 hours to obtain a reaction product; and centrifuging the reaction product in a centrifuge at the rotating speed of 4000 r/min for 10 min, washing for three times, collecting bottom precipitates, and performing freeze vacuum drying to obtain the andrographolide modified montmorillonite.
Example 3
The structural composition of the antibacterial detoxified feed additive provided in the embodiment is basically the same as that of the antibacterial detoxified feed additive provided in the embodiment 1, and the main difference is that: in the andrographolide-modified montmorillonite of this example, the adsorption amount of andrographolide was 8.00 mg/g.
The preparation method of andrographolide-modified montmorillonite provided in this example is basically the same as the preparation method provided in example 1, and the main difference is that:
treating andrographolide modified montmorillonite, performing ultrasonic extraction on 0.1 g of andrographis paniculata extract by adopting an ethanol solution with volume fraction of 75% for 20 min, adding 20 mL of distilled water, weighing 0.500 g of PEG composite modified montmorillonite, and reacting in a constant-temperature water bath oscillator under the condition of default pH value of a reaction system at the reaction temperature of 60 ℃ for 2 h under the reaction condition of 120 r/min and the reaction temperature of 120 ℃ to obtain a reaction product; and centrifuging the reaction product in a centrifuge at the rotating speed of 4000 r/min for 10 min, washing for three times, collecting bottom precipitates, and performing freeze vacuum drying to obtain the andrographolide modified montmorillonite.
Example 4
The structural composition of the antibacterial detoxified feed additive provided in the embodiment is basically the same as that of the antibacterial detoxified feed additive provided in the embodiment 1, and the main difference is that: in the andrographolide-modified montmorillonite of this example, the adsorption amount of andrographolide was 9.02 mg/g.
The preparation method of andrographolide-modified montmorillonite provided in this example is basically the same as the preparation method provided in example 1, and the main difference is that:
treating andrographolide modified montmorillonite by ultrasonically extracting 0.1 g of andrographis paniculata extract by using 75% ethanol solution with volume fraction for 20 min, adding 20 mL of distilled water, weighing 0.500 g of PEG composite modified montmorillonite, and reacting in a constant-temperature water bath oscillator under the conditions of 120 r/min, 10.0 pH value, 60 ℃ and 2 h to obtain a reaction product; and centrifuging the reaction product in a centrifuge at the rotating speed of 4000 r/min for 10 min, washing for three times, collecting bottom precipitates, and performing freeze vacuum drying to obtain the andrographolide modified montmorillonite.
Example 5
The structural composition of the antibacterial detoxified feed additive provided in the embodiment is basically the same as that of the antibacterial detoxified feed additive provided in the embodiment 1, and the main difference is that: in the andrographolide-modified montmorillonite of this example, the adsorption amount of andrographolide was 1.80 mg/g.
The preparation method of andrographolide-modified montmorillonite provided in this example is basically the same as the preparation method provided in example 1, and the main difference is that:
treating andrographolide modified montmorillonite by ultrasonically extracting 0.1 g of andrographis paniculata extract by using 75% ethanol solution with volume fraction for 20 min, adding 20 mL of distilled water, weighing 0.500 g of PEG composite modified montmorillonite, and reacting in a constant-temperature water bath oscillator under the conditions of 120 r/min, pH value of 5.0, reaction temperature of 60 ℃ and reaction time of 2 h to obtain a reaction product; and centrifuging the reaction product in a centrifuge at the rotating speed of 4000 r/min for 10 min, washing for three times, collecting bottom precipitates, and performing freeze vacuum drying to obtain the andrographolide modified montmorillonite.
Example 6
The structural composition of the antibacterial detoxified feed additive provided in the embodiment is basically the same as that of the antibacterial detoxified feed additive provided in the embodiment 1, and the main difference is that: in the andrographolide-modified montmorillonite of this example, the adsorption amount of andrographolide was 5.35 mg/g.
The preparation method of andrographolide-modified montmorillonite provided in this example is basically the same as the preparation method provided in example 1, and the main difference is that:
treating andrographolide modified montmorillonite, performing ultrasonic extraction on 0.100 g of andrographis paniculata extract by adopting 75% ethanol solution with volume fraction for 20 min, adding 20 mL of distilled water, weighing 1.000 g of PEG composite modified montmorillonite, and reacting in a constant-temperature water bath oscillator under the condition of default pH value of a reaction system at the reaction temperature of 60 ℃ for 2 h under the reaction condition of 120 r/min and the reaction temperature of 120 ℃ to obtain a reaction product; and centrifuging the reaction product in a centrifuge at the rotating speed of 4000 r/min for 10 min, washing for three times, collecting bottom precipitates, and performing freeze vacuum drying to obtain the andrographolide modified montmorillonite.
Example 7
The structural composition of the antibacterial detoxified feed additive provided in the embodiment is basically the same as that of the antibacterial detoxified feed additive provided in the embodiment 1, and the main difference is that: in the andrographolide-modified montmorillonite of this example, the amount of andrographolide adsorbed was 7.03 mg/g.
The preparation method of andrographolide-modified montmorillonite provided in this example is basically the same as the preparation method provided in example 1, and the main difference is that:
treating andrographolide modified montmorillonite, performing ultrasonic extraction on 0.100 g of andrographis paniculata extract by adopting 75% ethanol solution with volume fraction for 20 min, adding 20 mL of distilled water, weighing 0.500 g of PEG composite modified montmorillonite, and reacting in a constant-temperature water bath oscillator under the condition of default pH value of a reaction system at the reaction temperature of 60 ℃ for 1 h under the reaction condition of 120 r/min and the reaction temperature of 1 h to obtain a reaction product; and centrifuging the reaction product in a centrifuge at the rotating speed of 4000 r/min for 10 min, washing for three times, collecting bottom precipitates, and performing freeze vacuum drying to obtain the andrographolide modified montmorillonite.
Example 8
The embodiment provides a feed suitable for weaned piglets, which consists of a basic ration for the weaned piglets and the antibacterial and detoxified feed additive provided in the embodiment 1, wherein the additive amount of the antibacterial and detoxified feed additive is 1%. Wherein, calculated by mass percentage, the basic ration for the weaned piglets consists of 56.5 percent of corn, 15.0 percent of soybean meal, 8.0 percent of expanded soybean, 5.0 percent of wheat middling, 4.0 percent of fish meal, 3.5 percent of soybean oil, 2.5 percent of whey powder, 2.5 percent of glucose and 3 percent of premix, and each kilogram of premix contains 150 mg of Fe, 85 mg of Cu, 80 mg of Mn, 10000 IU of VA, 31200 IU of VD, 30 IU of VE, 11.5 mg of VB, 23.5 mg of VB, 61.4 mg of VB, 120.03 mg of VB, 30 mg of nicotinic acid, 15 mg of D-pantothenic acid and 0.14 mg of biotin; the basic daily ration for the weaned piglets comprises 18.32% of crude protein, 6.07% of crude fat, 2.41% of crude ash, 1.40% of lysine, 0.62% of sodium chloride, 0.59% of phosphorus and 0.81% of calcium, and the digestion energy is 13.80 MJ/Kg.
Example 9
The present embodiment provides a feed suitable for weaned piglets, which is composed of a basic ration for weaned piglets and the antibacterial and detoxified feed additive provided in embodiment 3 (the adsorption amount of andrographolide is 8.00 mg/g), and the addition amount of the antibacterial and detoxified feed additive is 1%.
Example 10
The present embodiment provides a feed suitable for weaned piglets, which is composed of a basic ration for weaned piglets and the antibacterial and detoxified feed additive (the adsorption amount of andrographolide is 1.80 mg/g) provided in embodiment 5, and the additive amount of the antibacterial and detoxified feed additive is 1%.
Example 11
The present example provides a feed suitable for weaned piglets, which is composed of a basic ration for weaned piglets and the antibacterial and detoxified feed additive provided in example 6 (the adsorption amount of andrographolide is 5.35 mg/g), and the addition amount of the antibacterial and detoxified feed additive is 1%.
The basic ration for the weaned pigs adopted in the feeds provided in examples 9 to 11 and comparative examples 1 to 3 below has the same raw material composition and nutritional ingredients as the basic ration for the weaned pigs in example 8.
Diarrhea effect test on piglets with different feeds
1. Test object
The selected weaned piglets are all the three-element long-growing hybrid weaned piglets with the same variety and similar weight, the number of the piglets is 126 in each half of the male and female, then the selected experimental animals are randomly divided into 7 groups which are respectively the feed provided in examples 8-11 and comparative examples 1-3, each group is provided with 3 repetitions, and each repetition is provided with 6 piglets.
Wherein, the comparative example 1 consists of basic daily ration of weaned pigs and montmorillonite simple mixed powder with the addition of 1 percent, and the composition of the montmorillonite simple mixed powder is the same as that of the montmorillonite simple mixed powder in the section 3 of the example 1 and the bacteriostasis performance verification of the antibacterial and detoxified feed additive provided by the example; comparative example 2 consists of basal ration for weaned piglets and 80 mg/kg of chlortetracycline antibiotic; comparative example 3 consisted of a basal diet for weaned piglets.
2. Test conditions
Weaned piglets are kept in the same closed pigsty, water is freely drunk, and dry powder is selected as feed. Pre-feeding basal diet for 2 days, then using Escherichia coli to counteract toxic substance, and injecting into abdominal cavity with 0.2 mL Escherichia coli K88 (concentration of 2.1 × 10)9one/mL), feeding the test feed after the diarrhea symptoms appear, observing and recording the diarrhea condition of the piglets, wherein the test period is 7 d.
3. Test results
After 24 h of escherichia coli challenge, all piglets in the treatment group showed diarrhea. After the test feed is fed, the piglets fed with the feed provided by the comparative example 3 have severe diarrhea, and have dehydration on the third day, and are treated by antibiotics on the fourth day to ensure the health of the piglets.
On the 5 th day of the feeding test, the diarrhea rate of the feed provided by the example 8 is reduced to 11 percent, which is lower than 22 percent of that of the group of the comparative example 2; the feed provided in example 9 was the same as the group of comparative example 2 on the fifth day of the feeding test, lower than that of comparative example 1; the diarrhea rate of the feed provided in example 10 on the fifth day of the feeding test was 67%, which was the same as that of comparative example 1; the diarrhea rate of the feed of example 11 was 61% on the fifth day of the feeding test, which was slightly lower than that of comparative example 1. While the diarrhea rate of piglets fed with the feed provided in comparative example 1 was 67%. On day 7 of the trial, diarrhea was controlled in piglets fed the feeds provided in example 8 and comparative example 2. Specific results are shown in table 1.
TABLE 1 piglet diarrhea test results table
Example 12
The present embodiment provides a feed suitable for chicks, which comprises a basal diet of chicks and the antibacterial and detoxified feed additive provided in embodiment 2, and the additive amount of the antibacterial and detoxified feed additive is 0.8%. The basal diet of the chicks mainly comprises 86% of corn, 4% of corn protein powder and 10% of soybean meal.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention and not to limit it; although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art will understand that: modifications to the specific embodiments of the invention or equivalent substitutions for parts of the technical features may be made; without departing from the spirit of the present invention, it is intended to cover all aspects of the invention as defined by the appended claims.
Claims (10)
1. An antibacterial detoxified feed additive is characterized by comprising andrographolide modified montmorillonite mainly composed of polyethylene glycol composite modified montmorillonite and andrographolide, wherein the andrographolide is adsorbed or intercalated in the crystal structure of the PEG composite modified montmorillonite.
2. The antibacterial and detoxified feed additive according to claim 1, wherein the adsorption amount of andrographolide in the andrographolide-modified montmorillonite is 1.80-10.33 mg/g.
3. The antibacterial and detoxified feed additive according to claim 1 or 2, characterized in that the andrographolide-modified montmorillonite is mainly prepared by the following method: mixing andrographolide and PEG composite modified montmorillonite in water, reacting at constant temperature and at a stirring speed of 80-200 r/min, and then centrifuging, washing and drying to obtain the andrographolide modified montmorillonite.
4. The antibacterial and detoxified feed additive according to claim 3, wherein the andrographolide-modified montmorillonite is mainly prepared by the following method: placing the andrographis paniculata extract in an ethanol solution with the volume fraction of more than or equal to 60% for ultrasonic extraction treatment, and adding water and the polyethylene glycol composite modified montmorillonite; stirring and reacting for 0.5-4 h under the conditions that the reaction pH value is 5-11 and the reaction temperature is 40-80 ℃; and then centrifuging, washing and drying to obtain the andrographolide modified montmorillonite.
5. The antibacterial and detoxified feed additive according to claim 1 or 2, wherein the polyethylene glycol complex modified montmorillonite comprises metal-ionized montmorillonite and polyethylene glycol, and the polyethylene glycol is intercalated between layers of the crystal structure of the metal-ionized montmorillonite.
6. The antibacterial and detoxified feed additive according to claim 5, wherein the PEG-modified montmorillonite is mainly prepared by the following method: dispersing metal ionized montmorillonite in water in a water bath, adding PEG, stirring for reaction, and then centrifuging, washing, drying, grinding and sieving to obtain the PEG composite modified montmorillonite.
7. The antibacterial and detoxified feed additive according to claim 6, wherein the metal-ionized montmorillonite is sodium-or potassium-montmorillonite, and is mainly prepared by the following steps: mixing raw ore montmorillonite powder with water to prepare ore pulp, adding a soluble carbonate solution, stirring and reacting under a constant temperature condition, and then centrifuging, washing, drying, grinding and sieving to prepare the metal ionized montmorillonite; the soluble carbonate solution is one or a mixture of sodium carbonate solution, potassium carbonate solution, sodium bicarbonate solution and potassium carbonate hydrogen solution.
8. A feed, which is characterized by comprising the antibacterial and detoxified feed additive as claimed in any one of claims 1 to 7, wherein the addition amount of the antibacterial and detoxified feed additive is less than or equal to 1%.
9. The feed of claim 8, further comprising an animal basal ration.
10. The feed of claim 9, wherein the animal basal ration is a basal ration for each growth stage of a livestock.
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|---|---|---|---|---|
| CN115024392A (en) * | 2022-06-15 | 2022-09-09 | 长沙傲鑫生物工程有限公司 | Preparation method for loading metal ion compound by using non-metallic mineral |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1372815A (en) * | 2002-03-18 | 2002-10-09 | 浙江大学 | Feed nano additive with health-care and growth promoting functions and its preparing process |
| WO2015081887A1 (en) * | 2013-12-05 | 2015-06-11 | 广西大学 | Acidic montmorillonite calcium hydroxide pharmaceutical composition, and preparation, product and application |
| CN105853459A (en) * | 2016-03-29 | 2016-08-17 | 东北农业大学 | Medicinal composition used for sows to prevent and treat diarrhea of newborn piglets, and compound traditional Chinese veterinary medicinal preparation method thereof |
| CN106615776A (en) * | 2016-11-16 | 2017-05-10 | 临沂大学 | Anti-mycotoxin feed additive for pigs as well as preparation method and application of anti-mycotoxin feed additive |
| CN107801839A (en) * | 2017-12-06 | 2018-03-16 | 江西省食品发酵研究所 | Add the preparation method of the fermentation pig feed of mold toxin sorbent |
| WO2020201586A1 (en) * | 2019-04-01 | 2020-10-08 | Lipidos Toledo S.A. | Supplement for use in animal feeding |
| CN113040278A (en) * | 2021-04-23 | 2021-06-29 | 河南工业大学 | Montmorillonite modified material and preparation method and application thereof |
-
2021
- 2021-04-23 CN CN202110441999.3A patent/CN113040279A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1372815A (en) * | 2002-03-18 | 2002-10-09 | 浙江大学 | Feed nano additive with health-care and growth promoting functions and its preparing process |
| WO2015081887A1 (en) * | 2013-12-05 | 2015-06-11 | 广西大学 | Acidic montmorillonite calcium hydroxide pharmaceutical composition, and preparation, product and application |
| CN105853459A (en) * | 2016-03-29 | 2016-08-17 | 东北农业大学 | Medicinal composition used for sows to prevent and treat diarrhea of newborn piglets, and compound traditional Chinese veterinary medicinal preparation method thereof |
| CN106615776A (en) * | 2016-11-16 | 2017-05-10 | 临沂大学 | Anti-mycotoxin feed additive for pigs as well as preparation method and application of anti-mycotoxin feed additive |
| CN107801839A (en) * | 2017-12-06 | 2018-03-16 | 江西省食品发酵研究所 | Add the preparation method of the fermentation pig feed of mold toxin sorbent |
| WO2020201586A1 (en) * | 2019-04-01 | 2020-10-08 | Lipidos Toledo S.A. | Supplement for use in animal feeding |
| CN113040278A (en) * | 2021-04-23 | 2021-06-29 | 河南工业大学 | Montmorillonite modified material and preparation method and application thereof |
Non-Patent Citations (7)
| Title |
|---|
| Y.H. SHI ET AL: "Efficacy of modified montmorillonite nanocomposite to reduce the toxicity of aflatoxin in broiler chicks", 《ANIMAL FEED SCIENCE AND TECHNOLOGY》, 31 December 2006 (2006-12-31), pages 138 - 148 * |
| 卢其明等: "聚乙二醇/蒙脱石插层复合物的制备及结构表征", 《华南农业大学学报(自然科学版)》, no. 01, 31 January 2004 (2004-01-31), pages 2 * |
| 樊安利: "穿心莲内酯和乙酰穿心莲内酯的微生物转化及活性比较研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》, 15 May 2007 (2007-05-15), pages 2 - 1 * |
| 王恩文: "《黏土基多孔颗粒材料吸附净化工业废水研究》", 31 July 2018, 中国农业大学出版社, pages: 17 * |
| 郑水林等: "《粉体表面改性》", 30 June 2019, 中国建材工业出版社, pages: 246 - 249 * |
| 马玉龙等: "纳米载铜蒙脱石对断奶仔猪腹泻、肠道菌群及肠粘膜形态的影响", 《中国兽医学报》, no. 02, 31 March 2007 (2007-03-31), pages 3 * |
| 高灵娟: "蒙脱石型有机/无机复合抗菌材料的制备及抑菌性能研究", 《中国优秀硕士学位论文全文数据库 农业科技辑》, 15 February 2020 (2020-02-15) * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115024392A (en) * | 2022-06-15 | 2022-09-09 | 长沙傲鑫生物工程有限公司 | Preparation method for loading metal ion compound by using non-metallic mineral |
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