Coated biological sulfur as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of feed additives, and particularly relates to coated biological sulfur as well as a preparation method and application thereof. The coated biological sulfur is prepared from a biological sulfur granule core and a coating film coated outside the biological sulfur granule core, and the average particle size of the coated biological sulfur granule is 10-80 meshes. The prepared coated biological sulfur is simple in formula and low in preparation cost, covers the special odor of the biological sulfur, is good in palatability, can be used as a feed additive enteric-coated preparation, can be intensively released and absorbed in intestinal tracts, can obviously improve the bioavailability of the biological sulfur, and is a safe, effective and stable feed additive.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of feed additives, and particularly relates to a coated biological sulfur and a preparation method and application thereof. BACKGROUND

[0002] At present, livestock breeding is facing increasing pressure from food safety and environmental protection. Antibiotics, as feed additives, have been widely used in livestock breeding due to their obvious disease resistance and growth promotion. However, the abuse of antibiotics has led to bacterial drug resistance, intestinal flora imbalance of livestock, and accumulation of residues in livestock products, which has seriously polluted the environment and harmed human health. Therefore, reducing the use of antibiotics or even not using antibiotics is the trend of long-term development of livestock breeding, and seeking green, environmentally friendly, safe and efficient antibiotic substitutes has become a research hotspot at home and abroad.

[0003] Biological sulfur is obtained by applying biological desulfurization and sulfur recovery technology, that is, allowing sulfides to be oxidized by specific microorganisms to obtain elemental sulfur, thereby treating wastewater and recycling sulfur resources. The recovered sulfur slurry is dehydrated to form a sulfur cake containing 60-65% solid matter, and the purity of sulfur can reach 95-98%. The recovered elemental sulfur is nanoscale biological sulfur, which is much safer than ordinary sulfur and can be used as a raw material for producing pesticides, fungicides, fertilizers, sulfuric acid and feed additives.

[0004] At present, there are still some problems in the research of biological sulfur feed additives. First, biological sulfur itself has a special odor and poor palatability, which will reduce the feed intake of animals when directly added to feed. Second, the development and utilization of biological sulfur products are not sufficient, and most of the sulfur cakes are directly discharged into the soil after dilution, without truly realizing the waste-to-resource. Third, the existing biological sulfur additives lack effective coating technology, which makes it difficult to control the release process in the animal digestive tract and affects its bioavailability and efficacy. Therefore, it is of great practical significance to develop a biological sulfur feed additive that can improve the palatability of biological sulfur, improve its stability and bioavailability. SUMMARY

[0005] To solve the above technical problems, the present application provides a coated biological sulfur, which is made of a biological sulfur particle core and a coating film wrapped outside the biological sulfur particle core.

[0006] The biological sulfur particle core, in terms of mass parts, comprises the following raw materials: 200-500 parts of biological sulfur, 50-150 parts of microcrystalline cellulose, 300-600 parts of starch, and 30-300 parts of PVP K30 solution.

[0007] The coating film, in mass parts, comprises: purified water 15 parts, talcum powder (1250 mesh) 3 parts, polyacrylic resin emulsion No. 15 parts, triethyl citrate 1 part; the average particle size of the coated bio-sulfur is 10-80 mesh.

[0008] Further, the bio-sulfur particle core, in mass parts, comprises: bio-sulfur 300-400 parts, microcrystalline cellulose 75-120 parts, starch 400-500 parts, PVP K30 solution 100-250 parts.

[0009] Preferably, the bio-sulfur particle core, in mass parts, comprises: bio-sulfur 350 parts, microcrystalline cellulose 100 parts, starch 450 parts, PVP K30 solution 200 parts.

[0010] Further, the PVP K30 solution is a 0.5% mass / volume aqueous solution.

[0011] Further, the polyacrylic resin emulsion No. 15 in the coating film is a 12.5% solid content alkaline water dispersion solution.

[0012] The application also provides a preparation method of the coated bio-sulfur, comprising the following steps:

[0013] (1) After the bio-sulfur is taken through an 80-mesh sieve, the bio-sulfur is mixed with microcrystalline cellulose, starch and PVP K30 solution to prepare a soft material;

[0014] (2) The prepared soft material is put into a rotary extrusion granulator and extruded and granulated through an 80-mesh sieve;

[0015] (3) After the granulation is completed, the uniform pellets are thrown by a spherical shot blasting machine, dried in a fluidized bed, sieved and granulated, and the bio-sulfur particle core is obtained;

[0016] (4) The required raw materials of the coating film are mixed and stirred according to the proportion to obtain a coating film solution;

[0017] (5) The bio-sulfur particle core is put into a coating fluidized bed, the coating process is set, and the coating film solution is sprayed to coat;

[0018] (6) After the coating is completed, the mixture is dried in the fluidized bed for 5-10 minutes, and the coated bio-sulfur is obtained.

[0019] Further, the coating process: gun pressure 0.3 bar, air inlet temperature 50℃, and coating film solution spraying rate 60 mL / min.

[0020] The application also provides a feed or feed additive containing the coated bio-sulfur.

[0021] The application also provides the use of the coated bio-sulfur in the preparation of feed or feed additive. Preferably, 1-5 kg of the coated bio-sulfur is added in each ton of basal diet to prepare the feed.

[0022] The application also provides the use of the coated bio-sulfur in the preparation of a preparation for improving the growth performance and / or diarrhea of farmed animals.

[0023] The application has the following advantages over the prior art:

[0024] The coated bio-sulfur prepared by the application can effectively inhibit intestinal pathogenic bacteria, regulate intestinal flora balance, and maintain intestinal health; at the same time, it can improve the digestive and absorptive capacity of the intestinal tract for nutrients and the feed utilization rate; enhance the body's resistance to pathogenic microorganisms, reduce the incidence of disease; promote the rapid growth of livestock and poultry, improve the production performance of livestock and poultry, and improve the quality of livestock and poultry products; compared with traditional antibiotics, the product of the application has the advantages of green, safety, environmental protection, and no residue; realizes the transformation of waste into treasure of bio-sulfur, and fills the gap left after the prohibition of traditional growth-promoting antibiotics. BRIEF DESCRIPTION OF DRAWINGS

[0025] Figure 1 Mice for acute toxicity test of bio-sulfur DETAILED DESCRIPTION

[0026] The application will be further described below in conjunction with the examples, and the described examples are part of the examples of the application, but not all the examples. Based on the examples in the application, all other examples obtained by those skilled in the art without creative labor fall within the scope of the application.

[0027] The bio-sulfur used in the following examples is self-made by Gansu Dabeinong Bioengineering Co., Ltd., and the production process is as follows: sodium thiosulfate is oxidized to elemental sulfur by sulfur bacillus in a reactor, the elemental sulfur is washed with purified water for 2 times, and then bio-sulfur is obtained through plate and frame pressure filtration and natural air drying, with a sulfur content of 95%.

[0028] Example 1

[0029] The preparation method of the coated bio-sulfur includes the following steps:

[0030] (1) Preparation of bio-sulfur particle core:

[0031] Take the following weight parts of raw materials: biogenic sulfur 200 parts (content 95%), microcrystalline cellulose 50 parts, starch 300 parts, 0.5% PVP K30 aqueous solution 30 parts.

[0032] The biogenic sulfur raw material is passed through an 80-mesh sieve, mixed with microcrystalline cellulose, starch and 0.5% PVP K30 aqueous solution to prepare a soft material; the prepared soft material is put into a rotary extrusion granulator and extruded and granulated through an 80-mesh sieve; after granulation, the uniform pellets are thrown into a spherical shot blasting machine, dried at 80°C in a fluidized bed, sieved and granulated, and obtained.

[0033] (2) Preparation of coating film:

[0034] Take the following weight parts of raw materials: purified water 15 parts, talc (1250 mesh) 3 parts, polyacrylic acid resin No. 6 emulsion 15 parts, triethyl citrate 1 part, mix and stir uniformly for standby. Among them, polyacrylic acid resin No. 6 emulsion is a weak alkaline aqueous dispersion with a solid content of 12.5% (w / w).

[0035] (3) Preparation of coated biogenic sulfur:

[0036] The mass ratio of biogenic sulfur particle core to coating film is 19:1. The biogenic sulfur particle core is put into the coating fluidized bed for coating, and the coating parameters are: gun pressure 0.3 bar, inlet air temperature 50°C, and the speed of injecting the coating film liquid is 60 mL / min; after coating, continue to dry and mix in the fluidized bed for 10 minutes, and obtain.

[0037] Example 2

[0038] The preparation method of coated biogenic sulfur includes the following steps:

[0039] (1) Preparation of biogenic sulfur particle core:

[0040] Take the following weight of raw materials: biogenic sulfur 500 parts, microcrystalline cellulose 150 parts, starch 600 parts, 0.5% PVP K30 aqueous solution 300 parts.

[0041] The biogenic sulfur raw material is passed through an 80-mesh sieve, mixed with microcrystalline cellulose, starch and 0.5% PVP K30 aqueous solution to prepare a soft material. The prepared soft material is put into a rotary extrusion granulator and extruded and granulated through an 80-mesh sieve; after granulation, the uniform pellets are thrown into a spherical shot blasting machine, dried at 80°C in a fluidized bed, sieved and granulated, and obtained.

[0042] (2) Preparation of coating film:

[0043] Take the following weight parts of raw materials: purified water 15 parts, talc (1250 mesh) 3 parts, polyacrylic acid resin No. 15 parts of emulsion, triethyl citrate 1 part, mix and stir uniformly for standby. Among them, polyacrylic acid resin No. 15 emulsion is a weak alkaline aqueous dispersion (Aqueous Dispersion) with a solid content of 12.5% (w / w).

[0044] (3) Preparation of coated bio-sulfur:

[0045] Bio-sulfur particle core: the mass ratio of coating film is 19:1. The bio-sulfur particle core is put into the coating fluidized bed for coating, and the coating parameters are: gun pressure 0.3 bar, inlet air temperature 50℃, and the speed of punching into the coating film liquid is 60 mL / min; after coating, continue to dry and mix in the fluidized bed for 10 minutes, and then get it.

[0046] Example 3

[0047] The preparation method of coated bio-sulfur includes the following steps:

[0048] (1) Preparation of bio-sulfur particle core:

[0049] Take the following weight of raw materials: bio-sulfur 300 parts, microcrystalline cellulose 80 parts, starch 400 parts, and 0.5% PVP K30 aqueous solution 100 parts.

[0050] The bio-sulfur raw material is passed through an 80-mesh sieve, mixed with microcrystalline cellulose, starch and 0.5% PVP K30 aqueous solution to prepare a soft material. The prepared soft material is put into a rotary extrusion granulator and extruded and granulated through an 80-mesh sieve; after granulation, it is thrown into a spherical shot blasting machine to form uniform pellets, which are dried in a fluidized bed at 80℃, sieved and granulated, and then obtained.

[0051] (2) Preparation of coating film:

[0052] Take the following weight parts of raw materials: purified water 15 parts, talc (1250 mesh) 3 parts, polyacrylic acid resin No. 15 parts of emulsion, triethyl citrate 1 part, mix and stir uniformly for standby. Among them, polyacrylic acid resin No. 15 emulsion is a weak alkaline aqueous dispersion (Aqueous Dispersion) with a solid content of 12.5% (w / w).

[0053] (3) Preparation of coated bio-sulfur:

[0054] Bio-sulfur particle core: the mass ratio of coating film is 19:1. The bio-sulfur particle core is put into the coating fluidized bed for coating, and the coating parameters are: gun pressure 0.3 bar, inlet air temperature 50℃, and the speed of punching into the coating film liquid is 60 mL / min; after coating, continue to dry and mix in the fluidized bed for 10 minutes, and then get it.

[0055] Example 4

[0056] The method for preparing the coated bio-sulfur includes the following steps:

[0057] (1) Preparation of bio-sulfur particle core:

[0058] Take the following raw materials with the following weights: bio-sulfur 400 parts, microcrystalline cellulose 120 parts, starch 500 parts, and 0.5% PVP K30 aqueous solution 250 parts.

[0059] Pass the bio-sulfur raw material through an 80-mesh sieve, and mix it with the microcrystalline cellulose, starch, and 0.5% PVP K30 aqueous solution to prepare a soft material. Put the prepared soft material into a rotary extrusion granulator and pass it through an 80-mesh sieve for extrusion granulation. After granulation, pass the small pellets through a spherical shot blasting machine to make them uniform, dry them in a fluidized bed at 80°C, and sieve and granulate them, and you will get the coated bio-sulfur.

[0060] (2) Preparation of coating film:

[0061] Take the following raw materials with the following weights: purified water 15 parts, talc (1250 mesh) 3 parts, polyacrylic acid resin No. 30 emulsion 15 parts, and triethyl citrate 1 part. Mix them well and use. The polyacrylic acid resin No. 30 emulsion is a weak alkaline aqueous dispersion with a solid content of 12.5% (w / w).

[0062] (3) Preparation of coated bio-sulfur:

[0063] Bio-sulfur particle core: the mass ratio of coating film to bio-sulfur particle core is 19:1. Put the bio-sulfur particle core into the coating fluidized bed for coating. The coating parameters are: gun pressure 0.3 bar, inlet air temperature 50°C, and the speed of injecting the coating film liquid is 60 mL / min. After coating, continue to dry and mix in the fluidized bed for 10 minutes, and you will get the coated bio-sulfur.

[0064] Example 5

[0065] The method for preparing the coated bio-sulfur includes the following steps:

[0066] (1) Preparation of bio-sulfur particle core:

[0067] Take the following raw materials with the following weights: bio-sulfur 350 parts, microcrystalline cellulose 100 parts, starch 450 parts, and 0.5% PVP K30 aqueous solution 200 parts.

[0068] The bio-sulphur raw material is sieved through an 80-mesh sieve, mixed with microcrystalline cellulose, starch and 0.5% PVP K30 aqueous solution to prepare a soft material. The prepared soft material is put into a rotary extrusion granulator to be extruded and granulated through an 80-mesh sieve; after granulation, the uniform pellets are thrown by a spherical shot blasting machine, dried at 80°C in a fluidized bed, sieved and granulated, and the coated bio-sulphur is obtained.

[0069] (2) Preparation of coating film:

[0070] The following raw materials are weighed: 15 parts of purified water, 3 parts of talc (1250 mesh), 15 parts of polyacrylic resin emulsion No. 8, and 1 part of triethyl citrate, which are mixed and stirred uniformly for use. The polyacrylic resin emulsion No. 8 is a weak alkaline aqueous dispersion with a solid content of 12.5% (w / w).

[0071] (3) Preparation of coated bio-sulphur:

[0072] The bio-sulphur core: the coating film ratio is 19:1. The bio-sulphur core is put into the coating fluidized bed for coating, and the coating parameters are: gun pressure 0.3 bar, inlet air temperature 50°C, and the speed of injecting the coating film liquid is 60 mL / min; after coating, the mixture is dried in the fluidized bed for 10 minutes, and the coated bio-sulphur is obtained.

[0073] Example 6

[0074] The preparation method of the coated bio-sulphur includes the following steps:

[0075] (1) Preparation of bio-sulphur core:

[0076] The following raw materials are weighed: 200 parts of bio-sulphur, 75 parts of microcrystalline cellulose, 300 parts of starch, and 200 parts of 0.5% PVP K30 aqueous solution.

[0077] The bio-sulphur raw material is sieved through an 80-mesh sieve, mixed with microcrystalline cellulose, starch and 0.5% PVP K30 aqueous solution to prepare a soft material. The prepared soft material is put into a rotary extrusion granulator to be extruded and granulated through an 80-mesh sieve; after granulation, the uniform pellets are thrown by a spherical shot blasting machine, dried at 80°C in a fluidized bed, sieved and granulated, and the coated bio-sulphur is obtained.

[0078] (2) Preparation of coating film:

[0079] The following raw materials are weighed: 15 parts of purified water, 3 parts of talc (1250 mesh), 15 parts of polyacrylic resin emulsion No. 8, and 1 part of triethyl citrate, which are mixed and stirred uniformly for use. The polyacrylic resin emulsion No. 8 is a weak alkaline aqueous dispersion with a solid content of 12.5% (w / w).

[0080] (3) Preparation of coated bio-sulfur:

[0081] Bio-sulfur particle core: the mass ratio of coating film to bio-sulfur particle core is 19:1. The bio-sulfur particle core is put into the coating fluidized bed for coating, and the coating parameters are as follows: gun pressure 0.3 bar, air inlet temperature 50℃, and the speed of punching into the coating film liquid is 60 mL / min; after coating, drying and mixing in the fluidized bed for 10 minutes are continued, and the coated bio-sulfur is obtained.

[0082] The feed additive of the present application is mixed with pig and chicken, and 500 g (calculated by bio-sulfur) of the feed additive is added to each ton of feed, and the addition amount can be increased to 1 kg (calculated by bio-sulfur) in special stages or poor feeding environment.

[0083] In order to further verify the practical application effect of the coated bio-sulfur prepared by the present application, the following test examples are provided to further illustrate the good effect of the feed additive of the present application.

[0084] Test Example 1: Acute Toxicity Test (LD 50 determination) of Bio-sulfur

[0085] 1. Pre-experiment

[0086] The purpose of this test is to evaluate the safety of bio-sulfur according to the Guidelines for Acute Toxicity (LD 50 determination) of Veterinary Drugs by determining the median lethal dose (LD 50 ) of bio-sulfur, and to provide a basis for the application of bio-sulfur as a feed additive in livestock.

[0087] Test drug: bio-sulfur, provided by the R&D Department of Gansu Dabeinong Biological Engineering Co., Ltd., self-made, sulfur content 95%, batch number: 240621.

[0088] Test animals: 16 Kunming mice, half male and half female, weighing 18-22 g, purchased from the GLP laboratory of Lanzhou University. The qualification certificate number is SCXK (Gan) 2023-0003.

[0089] The mice were purchased and acclimated for 3 days in a constant temperature, ventilated room, and randomly divided into 4 groups of 4 each (half male and half female), and fasted for 8 hours before administration (without water restriction). The bio-sulfur was prepared into a suspension solution with concentrations of 75, 150, 300, and 600 mg / mL using deionized water, and each mouse was given 0.2 mL of the solution, 4 times a day, with 3 hours between each administration, for a total of 3000 mg / kg, 6000 mg / kg, 12000 mg / kg, and 24000 mg / kg per day, as shown in Table 1. The mice were observed for 7 days after administration, and the toxic effects and characteristics of the side effects were recorded. The dead mice were autopsied, and the pathological changes were observed and recorded. The absolute lethal dose and the maximum tolerated dose were determined to prepare for the formal test.

[0090] Table 1: Grouping of acute toxicity pre-test

[0091]

[0092] After administration, the high-dose group of mice had restlessness, lethargy, weight loss, and less activity, and some mice had grayish and watery feces. The low-dose group of mice had normal eating, drinking, activity, and mental state. On the second day of examination, 3 mice in the 24000 mg / kg dose group and 1 mouse in the 12000 mg / kg dose group died, with gray powder and chyme-like foreign matter in the chest, subcutaneous hemorrhage, ammonia smell, gastric distension, and black-green abdominal cavity. No toxic reactions were observed in the low-dose group, and no mice died at the end of the test. The specific results are shown in Table 2.

[0093] Table 2: Results of acute toxicity pre-test

[0094]

[0095] According to the results of the pre-test, the absolute lethal dose was greater than 24000 mg / kg, and the maximum tolerated dose was 6000 mg / kg.

[0096] 2. Formal test

[0097] Test drug: Bio-sulfur, same as pre-test.

[0098] Test animals: 50 Kunming mice, half male and half female, weighing 18-22 g, purchased from the GLP laboratory of Lanzhou University. The certificate number is SCXK (Gan) 2023-0003.

[0099] Test method: the test method is the same as above. The pre-test dose was set at 24000 mg / kg, which was found to be the maximum limit of the biological sulfur suspension preparation during the preparation of the drug solution. Therefore, the formal test design Dm=24000 mg / kg, Dn=6000 mg / kg. According to the "Guidelines for Acute Toxicity of Veterinary Drugs (LD50 Determination)", 5 dose groups between 6000-24000 mg / kg can be calculated according to the following formula: 1 / k=lg-1[(lgDm-lgDn) / (n-1)], 1 / k is 1.414 according to the above formula, and the 5 dose groups are 6000, 8485, 12000, 16971, 24000 mg / kg respectively. According to the pre-test solution preparation method, 5 concentrations of biological sulfur suspension were prepared, and the mice were randomly divided into 5 groups, 10 in each group, half male and half female. The 5 test groups were given drugs according to the dose, with equal volume and different concentrations, 0.2 ml / 20g each time, 4 times, with an interval of 3 hours. After administration, the mice were observed for 7 days, and the toxic effects and characteristics of the mice were recorded. Autopsy was performed on the dead mice, and the toxic pathological changes were observed and recorded.

[0100] During the test, the high-dose group of mice showed restlessness, lethargy, emaciation, and less activity, a few mice were arched and sat like a dog, their eyes were closed, some mice had grayish loose stools, some mice had loose fur, and some mice died on the 2nd-4th day. The symptoms of the low-dose group of mice were milder, and they ate, drank, moved and were normal in 2-3 days. The specific results are shown in Table 3.

[0101] Table 3 Results of acute toxicity test

[0102]

[0103] The test results were imported into Bliss statistical software for processing, and the regression equation y(Probit)=-23.674+6.6425Log(D) was obtained, the median lethal dose LD 50 =20739 mg / kg, LD 50 (Feller correction) 95% confidence limit=17314-29650 mg / kg.

[0104] The above tests show that the oral administration of biological sulfur to mice has an LD 50 of 20739 mg / kg. According to the dose classification table of acute toxicity (LD 50 ) of chemicals in China: 501-5000 mg / kg is low toxicity, 5001 mg-15000 mg / kg is practically non-toxic, and more than 15000 mg / kg is non-toxic, indicating that biological sulfur is non-toxic and has good safety.

[0105] Test Example 2: Evaluation Test of Coated Bio-sulfur Quality

[0106] 1. Materials and Methods

[0107] 1.1 Materials and Equipment

[0108] Coated bio-sulfur additive samples: prepared according to the methods of Examples 1-6, batch numbers: 2409001, 2409002, 2409003, 2409004, 2409005, 2409006.

[0109] Instrumentation: ZRS-8G dissolution tester, Tianjin Haiyida. KQ2200B ultrasonic cleaner, Kunshan Ultrasonic Instrument Co., Ltd. 9030MBE digital air drying oven, Shanghai Boxin Industrial Co., Ltd. Medical Equipment Factory. Electronic balance of 100,000th, Mettler Toledo.

[0110] 1.2 Inspection

[0111] Characteristics: investigate the characteristics and odor of coated bio-sulfur additive

[0112] Particle size: according to the particle size requirements of the Chinese Veterinary Pharmacopoeia 2010 edition, the particle size of the sample was inspected, according to the particle size and particle size distribution determination method, the sample was weighed with a precision electronic balance, the coated bio-sulfur particles were placed in the upper layer of the specified pore size screen (the lower screen was equipped with a tight receiving container), and the standard operation method was maintained horizontally, and the screen was shaken and tapped for 3 minutes. The particles and powder that could not pass through the large pore size screen and the particles and powder that could pass through the small pore size screen were weighed with a precision electronic balance. The sum of the particles that could not pass through the No. 1 screen (10 mesh) and the particles that could pass through the No. 5 screen (80 mesh) should not exceed 15% of the test amount.

[0113] Loss on drying: the coated bio-sulfur particles were determined according to the determination method of loss on drying, the sample was weighed with a precision electronic balance, and an appropriate amount was placed in a flat weighing bottle that had been dried to a constant weight, the sample was dried to a constant weight at a temperature of 105°C, and then the sample was weighed with a precision electronic balance. The loss on drying of the test sample was calculated from the weight loss and the sample weight.

[0114] 1.3 Content Determination

[0115] Take the coated biological sulfur additive sample, grind thoroughly, then accurately weigh 0.54 g of the sample, add 50 ml of ethanol-potassium hydroxide titration solution (0.5 mol / L), add 10 ml of water, heat in a water bath to dissolve, and evaporate the ethanol (until there are no bubbles and no alcohol smell). Add 40 ml of water, insert a small funnel into the bottle neck, and boil for 10 minutes. Cool, carefully add 5 ml of hydrogen peroxide test solution, shake well, heat in a boiling water bath for 10 minutes, cool to room temperature, rinse the funnel and bottle walls with water, add 2 drops of methyl orange indicator, titrate with hydrochloric acid titration solution (0.5 mol / L), and correct the titration result with a blank test. Each 1 ml of ethanol-potassium hydroxide titration solution (0.5 mol / L) is equivalent to 8.015 mg of sulfur (S). Calculate the sulfur (S) content in the coated biological sulfur sample.

[0116] 1.4 Release determination

[0117] Acid release amount: The acid release amount of the coated biological sulfur additive was determined according to the release determination method (Chinese Veterinary Pharmacopoeia 2010 Edition Volume I). 900 mL of 0.1 mol / L hydrochloric acid solution was taken as the test dissolution medium and placed in the dissolution cup according to the standard operation. When the temperature of the dissolution medium reached 37°C ± 0.5°C and remained constant in this range. 5.4 g was weighed and placed into the dissolution cup. The instrument was started to reach the specified speed. After 2 hours, the solution was taken at the designated sampling point, filtered through a 100 mesh sieve. Take 100 ml of the filtrate and evaporate it in a water bath. Accurately add 50 ml of ethanol-potassium hydroxide titration solution (0.5 mol / L), add 10 ml of water, heat in a water bath to dissolve, and evaporate the ethanol (until there are no bubbles and no alcohol smell). Add 40 ml of water, insert a small funnel into the bottle neck, and boil for 10 minutes. Cool, carefully add 5 ml of hydrogen peroxide test solution, shake well, heat in a boiling water bath for 10 minutes, cool to room temperature, rinse the funnel and bottle walls with water, add 2 drops of methyl orange indicator, titrate with hydrochloric acid titration solution (0.5 mol / L), and correct the titration result with a blank test. Each 1 ml of ethanol-potassium hydroxide titration solution (0.5 mol / L) is equivalent to 8.015 mg of sulfur (S). Calculate the acid release amount of the sample.

[0118] Release in buffer: the release in buffer of the coated bio-sulfur additive was determined according to the release determination method (Chinese Veterinary Pharmacopoeia, 2010 edition, part I). The acid solution in each dissolution cup was discarded, and 900 mL of phosphate buffer (pH 6.86) at a temperature of 37 ℃ ± 0.5 ℃ was immediately added. The rotation speed was set to 30 r / min, and the operation was continued for 45 min. At the specified sampling point, the solution was taken in an appropriate amount and filtered through a 100-mesh sieve. 100 mL of the filtrate was taken and evaporated in a water bath. 50 mL of ethanol-potassium hydroxide titration solution (0.5 mol / L) was added, 10 mL of water was added, and the solution was dissolved in a water bath and the ethanol was evaporated (until there were no bubbles and no alcohol smell). 40 mL of water was added, a small funnel was inserted into the bottle neck, and it was boiled for 10 minutes. After cooling, 5 mL of hydrogen peroxide test solution was added dropwise, shaken well, and placed in a boiling water bath for 10 minutes. After cooling to room temperature, the funnel and the bottle wall were washed with water, 2 drops of methyl orange indicator solution were added, and the titration was performed with hydrochloric acid titration solution (0.5 mol / L). The titration result was corrected by a blank test. Every 1 mL of ethanol-potassium hydroxide titration solution (0.5 mol / L) was equivalent to 8.015 mg of sulfur (S). The release in buffer of the sample was calculated.

[0119] 2 Results and analysis

[0120] 2.1 Inspection results

[0121] After preparing the coated bio-sulfur according to the prescription amount in the examples, the inspection was carried out according to the requirements of Chinese Veterinary Pharmacopoeia, 2020 edition, part I for granules. The bio-sulfur particle core was round with obvious sulfur irritation. The coated bio-sulfur was white and round with a light epoxy resin taste. The particle size, moisture content, etc. met the requirements of the Pharmacopoeia. The results are shown in Table 4.

[0122] Table 4 Inspection of coated bio-sulfur

[0123]

[0124] 2.2 Content determination results

[0125] The content detection results of the coated bio-sulfur additive are shown in Table 5. According to the prescription in the examples, the theoretical sulfur content of the coated bio-sulfur was calculated to be between 32.69-37.61%, and the content determination was carried out according to the sulfur content determination method in Chinese Pharmacopoeia, 2015 edition, part I. The actual sulfur content detection results were between 30.87-35.77%.

[0126] Table 5 Sulfur content determination results of coated bio-sulfur

[0127]

[0128] 2.3 Release results

[0129] The results of the coated bio-sulfur release determination are shown in Table 6. The bio-sulfur feed additive release amount in the acid solution was between 2.99-14.48%, and the release amount of other samples was within 10% except sample 2409002. The bio-sulfur feed additive release amount in the buffer solution was between 67.18-84.03%. The release amount of other samples was more than 70% except sample 240901.

[0130] Table 6 Results of coated bio-sulfur release determination

[0131]

[0132] 3 Summary

[0133] According to the results of the coated bio-sulfur sulfur content and release determination, sample 2409005 is the best, followed by 2409003.

[0134] Test Example 3: Growth promotion test of coated bio-sulfur on piglets

[0135] The test pigs were 120 "Duchangda" weaned piglets with a body weight of about 6 kg, which were randomly divided into 3 test groups and 1 control group according to the principle of "similar body weight, half male and half female". Each treatment had 30 pigs, divided into 3 replicates, 10 pigs per replicate.

[0136] The test groups 1-2 added the coated bio-sulfur of the application (prepared according to Example 5, content 35.8%), the test group 1 added 1.4 kg of coated bio-sulfur additive (containing 500 g of bio-sulfur) per ton of feed, and the test group 2 added 4.2 kg of coated bio-sulfur additive (containing 1500 g of bio-sulfur) per ton of feed. The test group 3 added 400 g of 15% aureomycin premix (containing 60 g of aureomycin) per ton of feed. The control group did not add any additive product, and the test diet was designed according to the standard in the pig feeding standard (NY / T 65-2004) for 8-20 kg weight. The feed formula and its nutritional level are shown in Table 7.

[0137] Table 7 Test diet formula and its nutritional level

[0138]

[0139] The test was carried out in a certain ecological breeding Co., Ltd. in Wuwei City, Gansu Province. The test time was from September to October 2024, for a total of 30 days. The pre-feeding period was 7 days. The feed consumption and remaining amount were weighed and recorded 3 times a day. At the beginning and end of the test, the body weight was measured on an empty stomach, and the daily gain, feed conversion ratio, and diarrhea rate were calculated.

[0140] Daily gain (ADG) = (final weight - initial weight) / number of test days

[0141] Feed conversion ratio = feed intake / weight gain

[0142] Diarrhea case = diarrhea head x d number / (test pig head number x test d number)

[0143] Diarrhea index (%) = diarrhea head x d number / (test pig head number x test d number) x 100%

[0144] The data were statistically analyzed by SPSS 18.0 software, the final weight, daily weight gain and feed conversion ratio were compared by variance analysis, the diarrhea frequency was compared by χ² test, and the diarrhea index was calculated. The results are shown in Table 8.

[0145] Table 8 Anti-diarrhea and growth-promoting effects of biological sulfur feed additive on piglets

[0146]

[0147] Note: The same column comparison, different letters represent significant difference (P<0.05).

[0148] As shown in Table 2, the final weight and daily weight gain of test group 1 (500 ppm biological sulfur), test group 2 (1500 ppm biological sulfur) and test group 3 (60 ppm aureomycin) were higher than those of the control group, and the daily weight gain of test group 2 was the highest, which was 17.41% higher than that of the control group (P<0.05). The feed conversion ratio of test group 1, test group 2 and test group 3 was lower than that of the control group, and the feed conversion ratio of test group 2 was 11.42% lower than that of the control group (P<0.05).

[0149] In terms of prevention of diarrhea, the diarrhea index of test group 1, test group 2 and test group 3 was lower than that of the control group, and the diarrhea index of test group 2 was the lowest, which was 2.7%, 5.1% lower than that of the control group, and the difference was not significant.

[0150] In summary, the effects of test group 1 (500 ppm biological sulfur) and test group 3 (60 ppm aureomycin) were basically equivalent, and test group 2 (1500 ppm) had good effects on prevention and treatment of weaned piglet diarrhea and growth promotion. Considering the cost factor, it is recommended to add 1.4 kg / T (500 ppm biological sulfur) of coated biological sulfur additive in nursery pig feed.

[0151] The above only describes the preferred embodiments of the present application, and it should be noted that for ordinary skilled persons in the technical field, several improvements and refinements can be made without departing from the technical principles of the present application, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A coated biosulphur characterised in that, The coated bio-sulfur is made of a bio-sulfur core and a coating film wrapped outside the bio-sulfur core; The bio-sulfur core comprises, in mass parts, 200-500 parts of bio-sulfur, 50-150 parts of microcrystalline cellulose, 300-600 parts of starch and 30-300 parts of PVP K30 solution. The coating film comprises, in mass parts, 15 parts of purified water, 3 parts of talc, 15 parts of polyacrylic resin emulsion No. 15 parts of triethyl citrate.

2. The coated bio-sulfur of claim 1, wherein, The bio-sulfur core comprises, in mass parts, 300-400 parts of bio-sulfur, 75-120 parts of microcrystalline cellulose, 400-500 parts of starch and 100-250 parts of PVP K30 solution.

3. The coated bio-sulfur of claim 2, wherein, The bio-sulfur core comprises, in mass parts, 350 parts of bio-sulfur, 100 parts of microcrystalline cellulose, 450 parts of starch and 200 parts of PVP K30 solution.

4. The coated bio-sulfur of any one of claims 1-3, wherein, The polyacrylic resin emulsion No. 15 is an alkaline water dispersion with a solid content of 12.5%.

5. The coated bio-sulfur of any one of claims 1-3, wherein, The PVP K30 solution is an aqueous solution with a mass / volume percentage concentration of 0.5%.

6. A process for the preparation of the coated bio-sulphur of any one of claims 1 to 3, characterized in that, The method comprises the following steps: (1) After the bio-sulfur is taken through an 80-mesh sieve, the bio-sulfur is mixed with microcrystalline cellulose, starch and PVP K30 solution to prepare a soft material; (2) The prepared soft material is put into a rotary extrusion granulator and extruded and granulated through an 80-mesh sieve; (3) After the granulation, the uniform small pellets are thrown by a spherical shot blasting machine, dried in a fluidized bed and sieved and granulated to obtain the bio-sulfur core; (4) The required raw materials of the coating film are mixed and stirred according to the proportion to obtain a coating film liquid; (5) The bio-sulfur core is put into a coating fluidized bed, the coating process is set, and the coating film liquid is sprayed to coat the bio-sulfur core; (6) After the coating is completed, the coated bio-sulfur is mixed and dried in the fluidized bed for 5-10 minutes.

7. The method of claim 6, wherein, The mass ratio of the bio-sulfur core to the coating film is 19:

1.

8. The method of claim 6, wherein, The coating process: gun pressure 0.3 bar, air inlet temperature 50℃, and the spraying rate of the coating film liquid is 60 mL / min.

9. A feed or feed additive containing the coated bio-sulfur according to any one of claims 1-3.

10. Use of the coated bio-sulfur according to any one of claims 1-3 in the preparation of a feed or feed additive.

11. Use according to claim 10, characterized in that, Each ton of the base daily ration is added with 1-5 kg of the coated bio-sulfur to prepare the feed.

12. Use of the coated bio-sulfur according to any one of claims 1-3 in the preparation of a preparation for improving the growth performance and / or diarrhea of farmed animals.

Images