CN114431339A - Low-additive stability-enhancing microencapsulated potassium diformate feed additive and preparation method thereof - Google Patents
Low-additive stability-enhancing microencapsulated potassium diformate feed additive and preparation method thereof Download PDFInfo
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
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- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
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- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
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- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
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- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/02—Local antiseptics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
- B01J13/16—Interfacial polymerisation
Abstract
The invention discloses a low-additive stability-increasing microencapsulated potassium diformate feed additive and a preparation method thereof, wherein the preparation method comprises the following steps: preparing a potassium diformate core material, adding the potassium diformate core material into an oily solvent, and uniformly stirring to obtain a suspension; preparing a monomer solution; and regulating the temperature of the suspension to 45-55 ℃ under the protection of nitrogen, continuously stirring, dropwise adding the monomer solution into the suspension during stirring, cooling, washing, filtering, and drying at low temperature to obtain the low-addition stability-enhancing microencapsulated potassium diformate feed additive. According to the invention, the hydrophobic isolation wall material is formed outside the potassium diformate core material, and the process is controlled to contain no water, so that the influence of water on the potassium diformate is reduced in the coating process, and meanwhile, after the microencapsulation is completed, the obtained wall material has good hydrophobicity, the influence of the subsequent transportation and storage processes on the potassium diformate is effectively avoided, the adverse influence of the external environment on the potassium diformate is reduced, and the product has good moisture resistance and high stability.
Description
Technical Field
The invention relates to the technical field of potassium diformate, in particular to a low-additive stability-enhancing microencapsulated potassium diformate feed additive and a preparation method thereof.
Background
After weaning, piglets often have intestinal problems, which are manifested by emaciation, diarrhea, stunted development and even death. In order to relieve and prevent growth retardation and diseases caused by weaning stress of piglets, antibiotics are often added to the daily ration of weaned piglets. After being approved as feed additives in the 50 th century, antibiotics play an important role in preventing and treating animal diseases, improving animal production performance and breeding benefits and the like, and promote the development of animal husbandry. However, with the long-term use and intensive research of the feed antibiotics, the side effects are gradually highlighted, mainly including:
1. the microecological balance of the gastrointestinal tract of the livestock and poultry is destroyed, the immune system of the livestock and poultry is interfered, the resistance of the livestock and poultry to diseases is reduced, and the sustainable development of the animal husbandry is seriously threatened;
2. drug-resistant strains are generated, so that the cross inheritance and cross propagation of antibiotic resistance are caused;
3. residues are caused in animal products and environment, the safety of animal food is affected, and the human health is threatened.
Based on the negative effect of feed antibiotics, the application of antibiotics in livestock and poultry production has been completely prohibited in 2006 in the European Union, and in recent years, organic acid feed additives have been developed greatly because the organic acid feed additives can maintain the acidic environment of intestinal tracts, inhibit the growth of harmful bacteria such as escherichia coli, salmonella and the like and have no adverse effect on animals. Formic acid is the most acidic organic acid under the same unit weight, can inhibit the growth of harmful bacteria in intestinal tracts and promote the growth of animals when added into feed, but formic acid has the problems of pungent smell, strong corrosivity, poor palatability and the like, and limits the use of the formic acid in the feed. However, the organic acid additives have the problems of unstable application effect, large addition amount, high cost and the like at present, and limit the wide application of the organic acid additives in the feed industry.
The potassium diformate is a dimer formed by associating formic acid and potassium formate through hydrogen bonds, has a molecular formula of HCOOH & HCOOK, can be dissociated into the formic acid and the potassium formate in a weak acid and weak base environment, and can enter the intestinal tract to play a role in inhibiting bacteria and promoting growth.
At present, the potassium diformate still has the advantages of high component release speed, unstable application effect, large effective dosage, extremely easy moisture absorption, easy influence of environmental factors in the processing and storage processes, and the improvement of the rear-end processing technology of the potassium diformate solves the practical application problem of the potassium diformate and is beneficial to promoting the large-scale application and popularization of the potassium diformate in the feed industry.
Disclosure of Invention
The invention aims to solve the defects in the prior art and provides a low-additive stability-enhancing microencapsulated potassium diformate feed additive and a preparation method thereof.
A preparation method of a low-additive stability-enhancing microencapsulated potassium diformate feed additive comprises the following steps:
s1, grinding the potassium diformate, the porous silicon dioxide, the dispersing agent and the surfactant for 2-6h, maintaining the temperature of the system to be less than or equal to 50 ℃ in the grinding process, adding N, N' -methylene bisacrylamide and the initiator, and continuing grinding for 1-2h to obtain a potassium diformate core material; adding into oily solvent, and stirring at 30-40 deg.C to obtain suspension;
s2, adding N-vinyl caprolactam and N-tert-butyl acrylamide into ethanol, and uniformly stirring to obtain a monomer solution;
s3, under the protection of nitrogen, adjusting the temperature of the suspension to 45-55 ℃, continuously stirring, dropwise adding the monomer solution into the suspension during stirring, continuously stirring for 3-6h, cooling, washing, filtering, and drying at low temperature to obtain the low-additive stability-increasing microencapsulated potassium diformate feed additive.
The initiator is firstly dispersed in the potassium diformate core material, so that the monomer solution can be promoted to be polymerized on the surface of the core material to form a microcapsule wall material, the self-polymerization of the monomer is effectively avoided, and the encapsulation rate is reduced, and the encapsulation rate is high and can reach more than 85%.
Preferably, in S1, the mass ratio of potassium diformate, porous silica, dispersant, surfactant, N' -methylene-bisacrylamide and initiator is 1-5: 4-10: 0.1-1: 0.1-1: 0.1-0.2: 0.01-0.05.
Preferably, in S1, the oily solvent is xylene.
Preferably, in S1, the initiator is ammonium persulfate.
Preferably, in S1, the surfactant is at least one of polyoxyethylene octylphenol ether, sodium dodecyl sulfate, and sodium dodecyl benzene sulfonate.
Preferably, in S1, the diameter of the porous silica is 612-945 nm.
Preferably, in S1, the porous silica is prepared by the steps of: aging cotton fiber, washing, drying, crushing, dripping tetraethyl silicate, cleaning, drying and sintering.
Specifically, the porous silica is prepared by the following steps: immersing cotton fibers into a sodium hydroxide solution, aging for 10-20h at room temperature, filtering, washing, drying, crushing, adding into an ethanol solution, stirring, adding ammonia water, stirring uniformly, dropwise adding tetraethyl silicate under a stirring state, stirring at room temperature, filtering, ultrasonically cleaning, freeze-drying, sintering, heating to 760 ℃ at the speed of 10-20 ℃/min from room temperature, preserving heat for 1-3h, air-cooling to room temperature, and crushing to obtain the porous silicon dioxide.
Further, the mass ratio of the cotton fiber, the ammonia water and the tetraethyl silicate is 5-10: 1-3: 1-5, wherein the mass fraction of ammonia water is 10-20%.
Further, the concentration of the sodium hydroxide solution is 0.2 to 1 mol/L.
Further, the mixture is aged at room temperature and washed with water for 2-4 times.
Further, the mass fraction of the ethanol solution is 60-80%.
Further, before freeze drying, ultrasonic cleaning is carried out by adopting ethanol and water in sequence.
In the porous silicon dioxide, cotton fibers are aged by sodium hydroxide, a defect structure is formed on the surfaces of the fibers, tetraethyl silicate is hydrolyzed to form silicon dioxide nano particles, the silicon dioxide nano particles are deposited and distributed on the surfaces of the fibers with the defect structure, the porous silicon dioxide keeps the tubular structure of the fibers after sintering, meanwhile, a tube body is porous, the diameter of the porous silicon dioxide is 612-945nm, the particle diameter of the nano particles is 80-125nm, and the pore diameter is 150-300 nm.
Preferably, in S2, the mass ratio of N-vinyl caprolactam to N-tert-butyl acrylamide is 1-5: 5-15.
Preferably, in S3, the mass ratio of potassium diformate core materials to N-vinyl caprolactam is 6-16: 1-5.
A low-additive stability-increasing microencapsulated potassium diformate feed additive is prepared by adopting the preparation method of the low-additive stability-increasing microencapsulated potassium diformate feed additive.
The technical effects of the invention are as follows:
according to the invention, potassium diformate, an initiator and N, N' -methylene bisacrylamide are jointly dispersed in an oily solvent to form a potassium diformate core material, wherein N-vinyl caprolactam is adopted as a microencapsulation framework, hydrophobic N-tert-butyl acrylamide is adopted as a monomer, and the N-vinyl caprolactam and the hydrophobic N-tert-butyl acrylamide are matched on the surface of the core material to carry out interfacial free radical polymerization reaction and wrap the core material, so that the self-polymerization phenomenon of the hydrophobic monomer can be reduced, the wrapping efficiency is high, the microcapsule is of a core-shell structure, the hydrophobic effect is good, the microcapsule stably exists in a certain temperature and pH value environment, and the slow-release and isolation effects are good.
The potassium diformate and the porous silicon dioxide are compounded and ground, the affinity of the potassium diformate and the porous silicon dioxide is good, the potassium diformate enters a hollow structure of the porous silicon dioxide, the potassium diformate and the porous silicon dioxide are fixed on the porous silicon dioxide through hydrogen bond combination, and then microencapsulation is carried out, so that the enteric coating of the potassium diformate can be realized, the product can be dissolved in intestinal tracts, the dissolved potassium diformate and the porous silicon dioxide have hydrogen bond action, the retention time of the potassium diformate in the intestinal tracts can be prolonged, and the antibacterial effect is remarkable.
According to the invention, the hydrophobic isolation wall material is formed outside the potassium diformate core material, and the process is controlled to contain no water, so that the influence of water on the potassium diformate is reduced in the coating process, and meanwhile, after the microencapsulation is completed, the obtained wall material has good hydrophobicity, the influence of the subsequent transportation and storage processes on the potassium diformate is effectively avoided, the adverse influence of the external environment on the potassium diformate is reduced, and the product has good moisture resistance and high stability.
The invention can adjust the release speed of the potassium diformate, realize the extension of action time and the enteric coating of the potassium diformate, ensure that the effective component of the potassium diformate can reach the tail section of an intestinal tract, has good absorption effect of the potassium diformate, improves the bioavailability, has excellent antibacterial performance, effectively reduces the dosage of the prior potassium diformate and reduces the cost.
Drawings
FIG. 1 is a graph showing the pH change of potassium diformate microcapsules obtained in example 5 and comparative examples 1-2 when the microcapsules are soaked in simulated gastric fluid and simulated intestinal fluid for different periods of time.
FIG. 2 is a graph showing the time-dependent change of the bacteriostatic rate of the potassium diformate microcapsules obtained in example 5 and comparative examples 1-2.
Detailed Description
The present invention will be further illustrated with reference to the following specific examples.
Example 1
A preparation method of a low-additive stability-enhancing microencapsulated potassium diformate feed additive comprises the following steps:
I. immersing 5g of cotton fiber into 30g of sodium hydroxide solution with the concentration of 0.2mol/L, aging at room temperature for 10h, filtering, washing with water for 2 times, drying, crushing, adding into 60% ethanol solution with the mass fraction, stirring for 2h, then adding 1g of ammonia water with the mass fraction of 10% into the solution, stirring uniformly, dropwise adding 1g of tetraethyl silicate under the stirring state, stirring at room temperature for 5h at the stirring speed of 1000r/min, filtering, sequentially ultrasonically cleaning with ethanol and water, freeze-drying, adding into a sintering furnace, heating from the room temperature to 700 ℃ at the speed of 10 ℃/min, preserving heat for 1h, air-cooling to the room temperature, and crushing to obtain porous silicon dioxide;
II. Grinding 1g of potassium diformate, 4g of porous silicon dioxide, 0.1g of dispersing agent and 0.1g of lauryl sodium sulfate for 2h, maintaining the temperature of the system to be less than or equal to 50 ℃ in the grinding process, adding 0.1g N, N' -methylene bisacrylamide and 0.01g of ammonium persulfate, and continuing grinding for 1h to obtain a potassium diformate core material; adding into 60g xylene, stirring at 30 deg.C and 1000r/min to obtain suspension;
III, adding 1g N-vinyl caprolactam and 5g N-tert-butyl acrylamide into 20g of ethanol, and uniformly stirring to obtain a monomer solution;
IV, under the protection of nitrogen, adjusting the temperature of the suspension to 45 ℃ and continuously stirring, and dropwise adding a monomer solution into the suspension in the stirring process, wherein the mass ratio of potassium diformate core materials to N-vinyl caprolactam is 6: 1; and continuously stirring for 3 hours, cooling, washing for 2 times by using deionized water, filtering, conveying into an oven, and drying for 20 hours at 40 ℃ to obtain the low-additive stability-increasing microencapsulated potassium diformate feed additive.
Example 2
A preparation method of a low-additive stability-enhancing microencapsulated potassium diformate feed additive comprises the following steps:
I. immersing 10g of cotton fiber into 60g of sodium hydroxide solution with the concentration of 1mol/L, aging at room temperature for 20h, filtering, washing with water for 4 times, drying, crushing, adding into 80% ethanol solution with the mass fraction of 20%, stirring for 4h, then adding 3g of ammonia water with the mass fraction of 20%, stirring uniformly, dropwise adding 5g of tetraethyl silicate under the stirring state, stirring at room temperature for 10h at the stirring speed of 2000r/min, filtering, sequentially ultrasonically cleaning with ethanol and water, freeze-drying, adding into a sintering furnace, heating from room temperature to 760 ℃ at the speed of 20 ℃/min, preserving heat for 3h, air-cooling to room temperature, and crushing to obtain porous silicon dioxide;
II. Grinding 5g of potassium diformate, 10g of porous silicon dioxide, 1g of dispersing agent and 1g of sodium dodecyl benzene sulfonate for 6 hours, maintaining the temperature of the system to be less than or equal to 50 ℃ in the grinding process, adding 0.2g N, N' -methylene bisacrylamide and 0.05g of ammonium persulfate, and continuing grinding for 2 hours to obtain a potassium diformate core material; adding into 100g xylene, stirring at 40 deg.C and 2000r/min to obtain suspension;
III, adding 5g N-vinyl caprolactam and 15g N-tert-butyl acrylamide into 30g of ethanol, and uniformly stirring to obtain a monomer solution;
IV, under the protection of nitrogen, adjusting the temperature of the suspension to 55 ℃, continuously stirring, and dropwise adding a monomer solution into the suspension in the stirring process, wherein the mass ratio of potassium diformate core materials to N-vinyl caprolactam is 16: 5; and continuously stirring for 6 hours, cooling, washing for 6 times by using deionized water, filtering, conveying into an oven, and drying for 30 hours at 50 ℃ to obtain the low-additive stability-increasing microencapsulated potassium diformate feed additive.
Example 3
A preparation method of a low-additive stability-enhancing microencapsulated potassium diformate feed additive comprises the following steps:
I. immersing 6g of cotton fiber into 50g of sodium hydroxide solution with the concentration of 0.4mol/L, aging at room temperature for 18h, filtering, washing with water for 3 times, drying, crushing, adding into 65% ethanol solution with the mass fraction of 18%, stirring for 3.5h, then adding 1.5g of ammonia water with the mass fraction of 18%, stirring uniformly, dropwise adding 2g of tetraethyl silicate under the stirring state, stirring at room temperature for 8h at the stirring speed of 1200r/min, filtering, sequentially performing ultrasonic cleaning by using ethanol and water, freeze-drying, adding into a sintering furnace, heating to 720 ℃ at the room temperature at the speed of 17 ℃/min, preserving heat for 2.5h, air-cooling to room temperature, and crushing to obtain porous silicon dioxide;
II. Grinding 2g of potassium diformate, 8g of porous silicon dioxide, 0.2g of dispersing agent and 0.8g of lauryl sodium sulfate for 3h, maintaining the temperature of the system to be less than or equal to 50 ℃ in the grinding process, adding 0.17g N, N' -methylene bisacrylamide and 0.02g of ammonium persulfate, and continuing grinding for 1.8h to obtain a potassium diformate core material; adding into 70g xylene, stirring at 37 deg.C and 1200r/min to obtain suspension;
III, adding 4g N-vinyl caprolactam and 8g N-tert-butyl acrylamide into 28g of ethanol, and uniformly stirring to obtain a monomer solution;
IV, under the protection of nitrogen, adjusting the temperature of the suspension to 48 ℃, continuously stirring, and dropwise adding a monomer solution into the suspension in the stirring process, wherein the mass ratio of potassium diformate core materials to N-vinyl caprolactam is 14: 2; and continuously stirring for 5 hours, cooling, washing for 3 times by using deionized water, filtering, conveying into a drying oven, and drying for 23 hours at 48 ℃ to obtain the low-additive stability-increasing microencapsulated potassium diformate feed additive.
Example 4
A preparation method of a low-additive stability-enhancing microencapsulated potassium diformate feed additive comprises the following steps:
I. immersing 8g of cotton fiber into 40g of sodium hydroxide solution with the concentration of 0.8mol/L, aging at room temperature for 12h, filtering, washing with water for 3 times, drying, crushing, adding into 75% ethanol solution with the mass fraction of 12%, stirring for 2.5h, then adding 2.5g of ammonia water with the mass fraction of 12%, stirring uniformly, dropwise adding 4g of tetraethyl silicate under the stirring state, stirring at room temperature for 6h at the stirring speed of 1800r/min, filtering, sequentially performing ultrasonic cleaning by using ethanol and water, freeze-drying, adding into a sintering furnace, heating to 740 ℃ at the room temperature at the speed of 13 ℃/min, preserving heat for 1.5h, air-cooling to room temperature, and crushing to obtain porous silicon dioxide;
II. Grinding 4g of potassium diformate, 6g of porous silicon dioxide, 0.6g of dispersing agent and 0.2g of sodium dodecyl benzene sulfonate for 5 hours, maintaining the temperature of the system to be less than or equal to 50 ℃ in the grinding process, adding 0.13g N, N' -methylene bisacrylamide and 0.04g of ammonium persulfate, and continuing grinding for 1.2 hours to obtain a potassium diformate core material; adding into 90g xylene, stirring at 33 deg.C and 1800r/min to obtain suspension;
III, adding 2g N-vinyl caprolactam and 12g N-tert-butyl acrylamide into 22g of ethanol, and uniformly stirring to obtain a monomer solution;
IV, under the protection of nitrogen, adjusting the temperature of the suspension to 52 ℃, continuously stirring, and dropwise adding a monomer solution into the suspension in the stirring process, wherein the mass ratio of potassium diformate core materials to N-vinyl caprolactam is 8: 4; and continuously stirring for 4 hours, cooling, washing for 5 times by using deionized water, filtering, conveying into a drying oven, and drying for 27 hours at 42 ℃ to obtain the low-additive stability-increasing microencapsulated potassium diformate feed additive.
Example 5
A preparation method of a low-additive stability-enhancing microencapsulated potassium diformate feed additive comprises the following steps:
I. immersing 7g of cotton fiber into 45g of sodium hydroxide solution with the concentration of 0.6mol/L, aging at room temperature for 15h, filtering, washing with water for 3 times, drying, crushing, adding into 70% ethanol solution with the mass fraction, stirring for 3h, then adding 2g of ammonia water with the mass fraction of 15% into the solution, uniformly stirring, dropwise adding 3g of tetraethyl silicate under the stirring state, stirring at room temperature for 7h at the stirring speed of 1500r/min, filtering, sequentially ultrasonically cleaning with ethanol and water, freeze-drying, adding into a sintering furnace, heating from the room temperature to 730 ℃ at the speed of 15 ℃/min, preserving heat for 2h, air-cooling to the room temperature, and crushing to obtain porous silicon dioxide;
II. Grinding 3g of potassium diformate, 7g of porous silicon dioxide, 0.4g of dispersing agent and 0.5g of octylphenol polyoxyethylene ether for 4 hours, maintaining the temperature of the system to be less than or equal to 50 ℃ in the grinding process, adding 0.15g N, N' -methylene bisacrylamide and 0.03g of ammonium persulfate, and continuing to grind for 1.5 hours to obtain a potassium diformate core material; adding into 80g xylene, stirring at 35 deg.C and 1500r/min to obtain suspension;
III, adding 3g N-vinyl caprolactam and 10g N-tert-butyl acrylamide into 25g of ethanol, and uniformly stirring to obtain a monomer solution;
IV, under the protection of nitrogen, adjusting the temperature of the suspension to 50 ℃ and continuously stirring, and dropwise adding a monomer solution into the suspension in the stirring process, wherein the mass ratio of potassium diformate core materials to N-vinyl caprolactam is 11: 3; and continuously stirring for 4.5h, cooling, washing for 4 times by using deionized water, filtering, conveying into an oven, and drying for 25h at the temperature of 45 ℃ to obtain the low-additive stability-enhancing microencapsulated potassium diformate feed additive.
Comparative example 1
A preparation method of a microencapsulated potassium diformate feed additive comprises the following steps:
I. grinding 3g of potassium diformate, 0.15g N, N' -methylene bisacrylamide, 0.03g of ammonium persulfate and 0.5g of octylphenol polyoxyethylene ether for 5.5 hours, and maintaining the temperature of the system to be less than or equal to 50 ℃ in the grinding process to obtain a potassium diformate core material; adding into 80g xylene, stirring at 35 deg.C and 1500r/min to obtain suspension;
II. Adding 3g N-vinyl caprolactam and 10g N-tert-butyl acrylamide into 25g of ethanol, and uniformly stirring to obtain a monomer solution;
III, under the protection of nitrogen, adjusting the temperature of the suspension to 50 ℃, continuously stirring, and dropwise adding a monomer solution into the suspension in the stirring process, wherein the mass ratio of potassium diformate core materials to N-vinyl caprolactam is 11: 3; and continuously stirring for 4.5h, cooling, washing for 4 times by using deionized water, filtering, conveying into an oven, and drying for 25h at the temperature of 45 ℃ to obtain the microencapsulated potassium diformate feed additive.
Comparative example 2
The conventional preparation method of the potassium diformate microcapsule feed comprises the following steps:
(1) preparation of a core material: and (3) putting 1g of mesoporous silica into 20mL of potassium diformate solution with the mass fraction of 3%, mechanically stirring for 3h at 40 ℃, centrifuging, and drying for 12h at 50 ℃ to obtain the microcapsule core material.
(2) Preparation of core material/sodium alginate solution: weighing 1g of core material, adding the core material into 200mL of sodium alginate solution with the mass fraction of 2%, and stirring at 40 ℃ until the mixture is uniformly mixed to obtain solution I.
(3) Preparation of chitosan-calcium chloride solution: weighing 1.5g chitosan, adding into 150mL acetic acid solution with volume fraction of 2%, stirring at 40 deg.C to obtain uniform solution, adding 20mL CaCl with mass fraction of 15%2The solution is stirred evenly to obtain a solution II.
(4) Preparing the sustained-release microcapsule: and (3) sucking the solution I by using a needle tube with the inner diameter of 0.5mm, slowly dripping the solution I into 170mL of the solution II, curing for 30min until microcapsules are formed, washing the microcapsules until no chloride ions exist by using distilled water, and drying the microcapsules in an oven at 50 ℃ for 12h to obtain the microcapsules with the particle size of 2.0-2.5 mm.
The test was carried out using the potassium diformate microcapsules obtained in example 5 and comparative examples 1-2.
Test example 1
The products of example 5 and comparative example 2 were subjected to moisture absorption testing, test method: at 60% humidity, room temperature, 1g of each sample was placed on an electronic balance and the weight was recorded periodically to check the degree of moisture absorption, the test results are shown in the following table:
| Time | example 5 | Comparative example 2 |
| 0h | 1.00g | 1.00g |
| 2h | 1.00g | 1.02g |
| 4h | 1.00g | 1.05g |
| 8h | 1.00g | 1.06g |
| 16h | 1.01g | 1.07g |
From the above table, compared with the microencapsulated potassium diformate in the prior art, the microencapsulated potassium diformate product has obviously improved moisture absorption, has no moisture absorption phenomenon before 8 hours, and particularly has the moisture absorption rate of only 1% at 16 hours, and has good moisture resistance.
Test example 2
1.2g of each group of samples were placed in 200mL of a hydrochloric acid solution having a pH of 2.0 (simulated gastric fluid system) and 200mL of a PBS buffer solution having a pH of 7.2 (simulated intestinal system), and the solutions were stirred at a constant temperature of 37 ℃ and a speed of 80r/min, and the pH values of the solutions were measured at regular time intervals.
The results are shown in FIG. 1. As can be seen from fig. 1:
1. the potassium diformate microcapsules obtained in example 5 and comparative example 1 are soaked in simulated gastric juice for a long time, the pH value of the solution is hardly changed, and the situation that the microcapsule wall material is not cracked and the potassium diformate is not released in the environment is shown. While the potassium diformate microcapsule obtained in the comparative example 2 is soaked in simulated gastric juice, but the pH value is increased to 3, the applicant believes that the pH value is increased because the wall material (particularly chitosan) reacts under acidic conditions by adopting sodium alginate and chitosan as the wall material in the comparative example 2.
2. Each group of potassium diformate microcapsules are soaked in simulated intestinal fluid, the microcapsule wall materials are broken in an alkaline environment, so that potassium diformate is effectively released, but compared with the wall materials of the potassium diformate microcapsules obtained in comparative example 2, example 5 and comparative example 1, the wall materials of the potassium diformate microcapsules can better resist the alkaline environment, and therefore, the effective component of the potassium diformate can reach the tail section of an intestinal tract along with the intestinal peristalsis.
Test example 3
1.2g of each group of samples are put into PBS buffer solution with the pH value of 7.2, and then put into a constant-temperature water bath kettle at 37 ℃, and stirred under a magnetic stirrer with the rotating speed of 80r/min, so that the potassium diformate in the microcapsules is fully released. And (3) absorbing 5mL of slow release solution into a centrifugal tube marked previously by a liquid transfer gun every 0.5h, placing the tube into a centrifugal machine with the speed of 5000r/min for centrifugation for 30min, diluting the tube by 30 times by using distilled water, and performing absorbance test on each diluted slow release solution by using an atomic absorption spectrophotometer to convert the solution into the content of the potassium diformate in each slow release solution, thereby calculating the encapsulation rate.
The encapsulation rate is the content of potassium diformate in the microspheres/the initial adding amount of the potassium diformate multiplied by 100 percent
The results are as follows:
| test items | Envelope rate% |
| Example 5 | 85.4 |
| Comparative example 1 | 74.6 |
| Comparative example 2 | 61.2 |
As can be seen from the above table: the encapsulation efficiency of the potassium diformate microcapsule obtained in example 5 is highest, and comparative example 1 is slightly worse than that of example 5, the applicant believes that the adsorption capacity of mesoporous silica to potassium diformate is limited, while the adsorption of the potassium diformate in example 5 by adopting the tubular structure of porous silica has the advantages of large loading amount of the porous silica and high stability, and the encapsulation efficiency reaches more than 85%.
Test example 4
Each set of potassium diformate microcapsule samples was added to PBS buffer solution with pH 7.2 used in test example 2 at an addition amount of 4% (based on the actual content of potassium diformate), 2mL was added to a test tube containing 8mL of a culture medium, 100 μ L of bacterial suspension of escherichia coli cultured to the logarithmic phase was added, the mixture was treated in a water bath at 37 ℃ and a stirring speed of 220r/min, and absorbance at a wavelength of 630nm was measured with a visible spectrophotometer at 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 15 hours, and 18 hours, respectively, and the bacteriostasis rate was calculated according to the following formula, as shown in fig. 2.
Inhibition rate (OD)1-OD)/OD×100％
OD is the absorbance of the sample; OD1The absorbance of the microcapsule-free bacteria-containing culture solution is shown.
As can be seen from fig. 2: example 5 porous silica is adopted to adsorb potassium diformate, so that the potassium diformate is slowly released in intestinal tracts, and has long-acting sterilization and bacteriostasis, and the antibacterial rate is stably increased within 16 hours and can reach more than 90 percent at most; in comparative example 2, mesoporous silica is adopted to adsorb potassium diformate, but the antibacterial efficiency is short, and only the early-stage antibacterial efficiency is stable, and can reach 82% at most, but the antibacterial efficiency continuously decreases after 6 hours, and the continuous antibacterial effect in intestinal tracts is difficult to maintain; comparative example 1 does not adopt the adsorption structure to protect potassium diformate, so that the potassium diformate enters the intestinal tract and starts to be released, the antibacterial rate reaches the peak initially, and then is continuously reduced.
Test example 5
The potassium diformate microcapsules obtained in example 5 and comparative examples 1-2 are added into pig feed for feeding in groups, and the addition amount is 4% (according to the actual content of the potassium diformate). Each group of feeding objects are 10 healthy piglets with age of 28 days, after the piglets are fed for 14 days, the piglets are respectively weighed and the average weight gain of each group of piglets is calculated, whether the piglets have diarrhea or death phenomenon is recorded in the feeding process, and the diarrhea rate and the death rate are calculated, and the test results are shown in the following table:
| example 5 | Comparative example 1 | Comparative example 2 | |
| Average weight gain, kg | 5.4 | 4.8 | 4.3 |
| Daily intake of food, kg | 0.38 | 0.31 | 0.22 |
| The rate of |
0 | 0 | 30 |
| |
0 | 0 | 10 |
The table shows that the diarrhea and death phenomena do not occur in the example 5 and the comparative example 1, the growth performance of the example 5 is better, and the immunity and the growth performance of the piglets can be obviously improved after the piglet feed is used for feeding the piglets.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be considered to be within the technical scope of the present invention, and the technical solutions and the inventive concepts thereof according to the present invention should be equivalent or changed within the scope of the present invention.
Claims (10)
1. A preparation method of a low-additive stability-enhancing microencapsulated potassium diformate feed additive is characterized by comprising the following steps:
s1, grinding the potassium diformate, the porous silicon dioxide, the dispersing agent and the surfactant for 2-6h, maintaining the temperature of the system to be less than or equal to 50 ℃ in the grinding process, adding N, N' -methylene bisacrylamide and the initiator, and continuing grinding for 1-2h to obtain a potassium diformate core material; adding into oily solvent, and stirring at 30-40 deg.C to obtain suspension;
s2, adding N-vinyl caprolactam and N-tert-butyl acrylamide into ethanol, and uniformly stirring to obtain a monomer solution;
s3, under the protection of nitrogen, adjusting the temperature of the suspension to 45-55 ℃, continuously stirring, dropwise adding the monomer solution into the suspension during stirring, continuously stirring for 3-6h, cooling, washing, filtering, and drying at low temperature to obtain the low-additive stability-increasing microencapsulated potassium diformate feed additive.
2. The preparation method of the low-additive stability-enhancing microencapsulated potassium diformate feed additive according to claim 1, wherein in S1, the mass ratio of potassium diformate, porous silica, a dispersing agent, a surfactant, N' -methylene bisacrylamide and an initiator is 1-5: 4-10: 0.1-1: 0.1-1: 0.1-0.2: 0.01-0.05.
3. The method for preparing the low-additive stability-enhancing microencapsulated potassium diformate feed additive as claimed in claim 1, wherein in S1, the oily solvent is xylene.
4. The method for preparing the low-additive stability-enhancing microencapsulated potassium diformate feed additive according to claim 1, wherein in S1, the initiator is ammonium persulfate.
5. The method for preparing the microencapsulated potassium diformate feed additive with low additive and stability as claimed in claim 1, wherein in S1, the surfactant is at least one of octylphenol polyoxyethylene ether, sodium dodecyl sulfate and sodium dodecyl benzene sulfonate.
6. The method for preparing the low-additive stability-enhancing microencapsulated potassium diformate feed additive as claimed in claim 1, wherein in S1, the diameter of the porous silica is 612-945 nm.
7. The preparation method of the microencapsulated potassium diformate feed additive with low additive and stability as claimed in claim 1, wherein in S1, the porous silica is prepared by the following steps: aging cotton fiber, washing, drying, crushing, dripping tetraethyl silicate, cleaning, drying and sintering.
8. The preparation method of the low-additive stability-enhancing microencapsulated potassium diformate feed additive according to claim 1, wherein in S2, the mass ratio of N-vinyl caprolactam to N-tert-butyl acrylamide is 1-5: 5-15.
9. The preparation method of the low-additive stability-enhancing microencapsulated potassium diformate feed additive according to claim 1, wherein in S3, the mass ratio of potassium diformate core materials to N-vinyl caprolactam is 6-16: 1-5.
10. A low-additive stability-increasing microencapsulated potassium diformate feed additive, which is characterized by being prepared by the preparation method of the low-additive stability-increasing microencapsulated potassium diformate feed additive of any one of claims 1 to 9.
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Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001038193A (en) * | 1999-07-28 | 2001-02-13 | Nippon Millipore Kk | Production of composite silica microcapsule, and method for controlling immobilization and slow releasing action of core substance of composite silica microcapsule |
| CN1452882A (en) * | 2003-05-23 | 2003-11-05 | 黄逸强 | Feed additive |
| JP2007121346A (en) * | 2005-10-25 | 2007-05-17 | Osaka Organic Chem Ind Ltd | Coated film forming resin composition |
| CN101283735A (en) * | 2007-08-10 | 2008-10-15 | 佛山市海纳川药业有限公司 | Microcapsule acidifier and its preparation method |
| WO2010113176A2 (en) * | 2009-03-31 | 2010-10-07 | Reliance Life Sciences Pvt. Ltd. | Novel copolymers for controlled release delivery system |
| US20110095227A1 (en) * | 2008-06-27 | 2011-04-28 | Gregor Herth | Retarded superabsorbent polymers |
| CN105112034A (en) * | 2015-08-11 | 2015-12-02 | 中国石油天然气股份有限公司 | High temperature resistant gel diverting agent and manufacturing method therefor and application thereof |
| CN109731103A (en) * | 2019-01-20 | 2019-05-10 | 桂林理工大学 | P-zeolite-chitin-sodium alginate-potassium diformate sustained-release antibacterial agent preparation method |
| CN110302188A (en) * | 2019-05-10 | 2019-10-08 | 郑州大学 | A kind of preparation method of the pharmaceutical composition of the hydrophobic associated polymer of anti-Alzheimer disease |
| CN112244163A (en) * | 2020-10-14 | 2021-01-22 | 四川省旺达饲料有限公司 | Antibiotic-free piglet feed additive and preparation method and application method thereof |
| CN112641001A (en) * | 2020-12-14 | 2021-04-13 | 重庆市六九畜牧科技股份有限公司 | Anti-coating compound acidifier |
| CN113801267A (en) * | 2021-09-24 | 2021-12-17 | 长春工业大学 | Thermosensitive polymer nano-microsphere for profile control and flooding and preparation method thereof |
-
2022
- 2022-02-14 CN CN202210134636.XA patent/CN114431339B/en active Active
Patent Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001038193A (en) * | 1999-07-28 | 2001-02-13 | Nippon Millipore Kk | Production of composite silica microcapsule, and method for controlling immobilization and slow releasing action of core substance of composite silica microcapsule |
| CN1452882A (en) * | 2003-05-23 | 2003-11-05 | 黄逸强 | Feed additive |
| JP2007121346A (en) * | 2005-10-25 | 2007-05-17 | Osaka Organic Chem Ind Ltd | Coated film forming resin composition |
| CN101283735A (en) * | 2007-08-10 | 2008-10-15 | 佛山市海纳川药业有限公司 | Microcapsule acidifier and its preparation method |
| US20110095227A1 (en) * | 2008-06-27 | 2011-04-28 | Gregor Herth | Retarded superabsorbent polymers |
| WO2010113176A2 (en) * | 2009-03-31 | 2010-10-07 | Reliance Life Sciences Pvt. Ltd. | Novel copolymers for controlled release delivery system |
| CN105112034A (en) * | 2015-08-11 | 2015-12-02 | 中国石油天然气股份有限公司 | High temperature resistant gel diverting agent and manufacturing method therefor and application thereof |
| CN109731103A (en) * | 2019-01-20 | 2019-05-10 | 桂林理工大学 | P-zeolite-chitin-sodium alginate-potassium diformate sustained-release antibacterial agent preparation method |
| CN110302188A (en) * | 2019-05-10 | 2019-10-08 | 郑州大学 | A kind of preparation method of the pharmaceutical composition of the hydrophobic associated polymer of anti-Alzheimer disease |
| CN112244163A (en) * | 2020-10-14 | 2021-01-22 | 四川省旺达饲料有限公司 | Antibiotic-free piglet feed additive and preparation method and application method thereof |
| CN112641001A (en) * | 2020-12-14 | 2021-04-13 | 重庆市六九畜牧科技股份有限公司 | Anti-coating compound acidifier |
| CN113801267A (en) * | 2021-09-24 | 2021-12-17 | 长春工业大学 | Thermosensitive polymer nano-microsphere for profile control and flooding and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 孟祥俭等: "二甲酸钾微胶囊的构建与缓释抑菌性", 精细化工, vol. 36, no. 11, pages 2252 - 2258 * |
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