Production process of aureomycin premix

Abstract

The invention relates to the technical field of antibiotic production, in particular to a production process of an aureomycin premix. The invention provides a production process of an aureomycin premix, which comprises the following specific steps: adding aureomycin fermentation liquor into a composite carrier, mixing, and carrying out plate frame filtration to obtain a filter cake with the water content of 50%; crushing the filter cake to obtain a wet material, adding aureomycin powder into the wet material, and reducing the water content to be less than 40%; adding an adhesive into the wet material and uniformly mixing; granulating the wet material by using a granulator, and then collecting a wet granular material; and drying the wet granulated material in a fluidized bed, and screening the dried material to obtain a 20-80-mesh material. By optimizing the process, the particle yield of the aureomycin premix is remarkably improved, meanwhile, powder residues are greatly reduced, efficient recycling of the screened powder is achieved, and raw material loss is reduced.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of antibiotic production, and particularly relates to a production process of chlortetracycline premix. BACKGROUND

[0002] Chlortetracycline (CTC) is commonly known as chlortetracycline premix, also known as chlortetracycline, which is a derivative of tetracycline. The main component is chlortetracycline calcium salt. As an important member of tetracycline antibiotics, chlortetracycline occupies a key position in the field of veterinary drugs due to its broad-spectrum and high-efficiency antibacterial properties. Chlortetracycline is widely used in the breeding industry and is a very effective veterinary product. It can effectively inhibit the growth of harmful bacteria, maintain the balance of intestinal microecology, thereby improving feed conversion rate, reducing breeding cost, and promoting the healthy growth of animals. Compared with traditional antibiotics, chlortetracycline has the advantages of high efficiency, low toxicity, and difficulty in developing drug resistance. It has a significant effect in preventing and treating bacterial infections in animals and has a broad market prospect.

[0003] At present, chlortetracycline premix is mainly produced by biological fermentation method. The fermentation is carried out by using Streptomyces aureus which can produce chlortetracycline, then heavy calcium is added to the fermentation liquor for extraction of chlortetracycline, and then chlortetracycline premix is obtained through the steps of plate and frame filtration, drying, screening and mixing. However, this process has many deficiencies, such as low particle ratio, high raw material loss, low utilization rate, and insufficient particle uniformity, which affects the subsequent application effect of the product. Therefore, it is urgent to develop a chlortetracycline premix production process with energy saving and economic benefit. SUMMARY

[0004] In order to solve the above technical problems, the present application provides a production process of chlortetracycline premix, which comprises the following steps:

[0005] S1: chlortetracycline fermentation liquor is added to a composite carrier at a ratio of 7% w / v, the composite carrier is made of chlortetracycline powder and heavy calcium powder, and the fermentation liquor and the carrier are fully mixed, then plate and frame filtration is carried out to obtain a filter cake with a water content of 45% to 55%;

[0006] S2: the filter cake is crushed to obtain wet material, and the wet material is added to chlortetracycline powder and the water content is reduced to below 40%;

[0007] S3: the wet material of S2 is added to sodium carboxymethyl cellulose with a weight ratio of not less than 5‰ and mixed uniformly;

[0008] S4: the S3 wet material is granulated by a granulator, the mesh size of the granulator is controlled to be no more than 3 mm, and the wet granulated material is collected; the wet granulated material is dried by a fluidized bed, and the dried material is screened to obtain a 20-80 mesh material; and the 20 mesh oversize material is crushed and rescreened, and the 80 mesh undersize material is used in S1.

[0009] Further, the step S1 composite carrier is made of aureomycin powder and heavy calcium powder in a weight ratio of (1-5):(2-6).

[0010] Preferably, the step S1 composite carrier is made of aureomycin powder and heavy calcium powder in a weight ratio of (1-3):(4-6).

[0011] Preferably, the step S1 composite carrier is made of aureomycin powder and heavy calcium powder in a weight ratio of 3:4.

[0012] Further, the water content of the step S2 wet material is reduced to 30%-38%.

[0013] Preferably, the water content of the step S2 wet material is reduced to 36%.

[0014] Further, the step S3 sodium carboxymethyl cellulose is added in an amount of 5‰-9‰.

[0015] Further, the mesh size of the step S4 granulator is 1-3 mm.

[0016] Further, the titer of the aureomycin fermentation broth is 28500 U / mL.

[0017] The application also provides an aureomycin premix prepared by the above production process.

[0018] The application has the following beneficial effects over the prior art:

[0019] The application significantly improves the granule yield of the aureomycin premix by optimizing the process, greatly reduces the residue of the powder, realizes efficient reuse of the undersize powder, and reduces the loss of raw materials; by precisely controlling the moisture of the wet material, the mixing uniformity of sodium carboxymethyl cellulose, and the drying parameters of the fluidized bed, high-proportion (20-80 mesh) uniform granules are obtained, the product stability and production efficiency are improved, and energy saving and consumption reduction and economic benefits are achieved. BRIEF DESCRIPTION OF DRAWINGS

[0020] Figure 1 The application is an aureomycin premix production process flow chart.

[0021] Figure 2 The application is an aureomycin premix production process flow chart.

[0022] Figure 3 To use different proportions of adhesives to affect the proportion of powder.

[0023] Figure 4 The material produced by different test groups. DETAILED DESCRIPTION

[0024] The application will be further described in conjunction with the examples. Those skilled in the art should understand that the examples are only for illustration and do not constitute any limitation on the application.

[0025] Example 1 Production process of aureomycin premix

[0026] The production process of aureomycin premix in this example is shown in Figure 1 The specific steps are as follows:

[0027] (1) Take a certain amount of aureomycin fermentation broth, add a certain proportion (w / v) of composite carrier, the carrier is mixed with aureomycin powder and heavy calcium powder, mix the fermentation broth and the carrier thoroughly, then perform plate and frame filtration to obtain a filter cake with a water content of 50%;

[0028] (2) Crush the filter cake and further add aureomycin powder to the crushed wet particles, reduce the moisture content of the wet material to a certain proportion;

[0029] (3) Add a certain proportion (w / w) of sodium carboxymethyl cellulose to the wet material and mix thoroughly in a mixer until the material state is uniform;

[0030] (4) Granulate the material with a granulator, control the screen mesh size of the granulator, and collect the wet granular material. Uniformly feed the wet granular material into a fluidized bed for drying, and sieve the dried material to obtain 20-80 mesh material. The 20 mesh sieve material is crushed and sieved again, and the 80 mesh sieve material is used in step (1).

[0031] Example 2 Selection of composite carrier proportion

[0032] The production process of aureomycin premix in this example is the same as in Example 1, and the amount of aureomycin fermentation broth used is 1 m 3 , and the measured titer is 28500 U / mL.

[0033] Step (1) sets up different proportions of composite carrier experimental groups 1-6 and a control group.

[0034] Among them:

[0035] The proportions (w / v) of aureomycin powder to heavy calcium in experimental groups 1-6 are 1:6, 2:5, 3:4, 4:3, 5:2, and 6:1, respectively; and the control group adds 7% heavy calcium instead of the composite carrier.

[0036] Step (2) The moisture content of the wet material is reduced to 30%.

[0037] Step (3) The sodium carboxymethyl cellulose is added at a ratio of 3 ‰.

[0038] Step (4) The mesh size of the granulator screen is selected to be 3 mm.

[0039] The experimental results show (see Figure 2 ), the yield of aureomycin in the control group is the highest, reaching 86%. When part of the heavy calcium is replaced by aureomycin powder, the yield gradually decreases, but in the compound carrier group with a ratio of aureomycin powder to heavy calcium of 3:4, the yield can still be maintained at 84%. Since the goal of this experiment is to increase the amount of powder added as much as possible while reducing yield loss, the compounding ratio of 3:4 is more reasonable.

[0040] Example 3: Selection of moisture content of wet material

[0041] In this example, the production process of aureomycin premix is the same as in Example 1, and the amount of aureomycin fermentation broth used is 1 m 3 , and the titer is determined to be 28500 U / mL.

[0042] Step (1) Add the compound carrier with a ratio of aureomycin powder to heavy calcium of 3:4.

[0043] Step (2) The moisture content of the wet material is reduced to 40%, 38%, 36%, 34%, 32%, and 30%, respectively.

[0044] Step (3) The sodium carboxymethyl cellulose is added at a ratio of 3 ‰.

[0045] Step (4) The mesh size of the granulator screen is selected to be 3 mm.

[0046] The experimental results are shown in Table 1. When aureomycin powder is added to reduce the moisture content to more than 40%, the wet granules are prone to stick to the screen during the granulation process. If the moisture content is controlled at 38%, although the sticking to the screen is reduced, there is still a small amount of sticking, and the granulation time is longer. Further increasing the amount of powder added to reduce the moisture content to less than 34% solves the sticking problem, but because the wet material is too dry, the granules are loose, and there is more fine powder produced after drying. Therefore, considering the granulation effect and product quality, it is recommended to control the moisture content in the range of 34% to 38%, with 36% as the optimal value.

[0047] Table 1: Results of selection of moisture content of wet material

[0048]

[0049] Example 4: Selection of the ratio of binder

[0050] The production process of aureomycin premix in this example is the same as that in Example 1, and the use amount of aureomycin fermentation liquor is 1 m 3 , and the determined titer is 28500 U / mL.

[0051] Step (1) adding aureomycin powder and heavy calcium carbonate in a ratio of 3:4.

[0052] Step (2) reducing the moisture content of the wet material to 36% respectively.

[0053] Step (3) adding sodium carboxymethyl cellulose in a ratio of 1 ‰, 3 ‰, 5 ‰, 7 ‰, 9 ‰ respectively.

[0054] Step (4) selecting 3 mm as the screen mesh size of the granulator.

[0055] The experimental results are shown in Table 1. Figure 3 After adding the binder sodium carboxymethyl cellulose, the proportion of powder significantly decreased, and when the addition amount of sodium carboxymethyl cellulose reached 5 ‰ or more, the proportion of powder remained basically unchanged. Therefore, considering the proportion of powder and the addition cost of the binder, 5 ‰ was selected as the optimal addition amount.

[0056] Example 5: Selection of screen mesh size of granulator

[0057] The production process of aureomycin premix in this example is the same as that in Example 1, and the use amount of aureomycin fermentation liquor is 1 m 3 , and the determined titer is 28500 U / mL.

[0058] Step (1) adding aureomycin powder and heavy calcium carbonate in a ratio of 3:4.

[0059] Step (2) reducing the moisture content of the wet material to 36% respectively.

[0060] Step (3) adding sodium carboxymethyl cellulose in a ratio of 5 ‰.

[0061] Step (4) selecting 1 mm, 2 mm, 3 mm, 4 mm, 5 mm as the screen mesh size of the granulator.

[0062] The experimental results are shown in Table 2. Considering the screening time and the proportion of 20 mesh sieve, the particles prepared by using 3 mm screen mesh have a passing rate of 20 mesh sieve of only 4.7%, which can be the best choice.

[0063] Table 2: Results of selection of screen mesh size of granulator

[0064]

[0065]

[0066] Test Example 1

[0067] The preparation process of aureomycin premix was tested, and test group 1, test group 2 and test group 3 were set. The use amount of aureomycin fermentation liquor was 1m 3 , and the determined titer was 28500U / mL.

[0068] Test group 1:

[0069] (1) Take aureomycin fermentation liquor (28500U / mL) 1m 3 , add calcium carbonate according to the proportion of 7% (w / v), mix the fermentation liquor and the carrier, then perform plate and frame filtration, and control the water content of the filter cake to be 30%;

[0070] (2) The filter cake is crushed to obtain wet granules. The wet granules are granulated by a granulator, the screen mesh aperture of the granulator is controlled to be 3mm, and the wet granular material is collected. The wet granular material is uniformly fed into a fluidized bed for drying, and the dried material is sieved to obtain 20-80 mesh material.

[0071] Test group 2:

[0072] (1) Take aureomycin fermentation liquor (28500U / mL) 1m 3 , add a composite carrier according to the proportion of 7% (w / v), the composite carrier is prepared by mixing aureomycin powder and calcium carbonate powder, the weight ratio of aureomycin powder to calcium carbonate is 3:4, mix the fermentation liquor and the carrier, then perform plate and frame filtration, and obtain a filter cake with a water content of 50%;

[0073] (2) The filter cake is crushed, and aureomycin powder is further added to the crushed wet granules, so that the water content of the wet material is reduced to 36%;

[0074] (3) The wet material is granulated by a granulator, the screen mesh aperture of the granulator is controlled to be 3mm, and the wet granular material is collected. The wet granular material is uniformly fed into a fluidized bed for drying, and the dried material is sieved to obtain 20-80 mesh material, the material above the 20 mesh sieve is crushed and sieved again, and the material below the 80 mesh sieve is fed into step (1).

[0075] Test group 3:

[0076] (1) Take aureomycin fermentation liquor (28500U / mL) 1m 3 , add a composite carrier according to the proportion of 7% (w / v), the composite carrier is prepared by mixing aureomycin powder and calcium carbonate powder, the weight ratio of aureomycin powder to calcium carbonate is 3:4, mix the fermentation liquor and the carrier, then perform plate and frame filtration, and obtain a filter cake with a water content of 50%;

[0077] (2) The filter cake is crushed, and aureomycin powder is further added to the crushed wet granules, so that the water content of the wet material is reduced to 36%;

[0078] (3) Add the wet material into 5‰ (w / w) sodium carboxymethyl cellulose, and mix in a mixer until the material is uniform;

[0079] (4) Granulate the material with a granulator, control the mesh size of the granulator to be 3 mm, and collect the wet granular material. Uniformly feed the wet granular material into a fluidized bed for drying, and sieve the dried material to obtain 20-80 mesh material. Crush the 20 mesh oversize and sieve again, and feed the 80 mesh undersize into step (1).

[0080] Table 3 Test results of different groups

[0081]

[0082] The test results are shown in Table 3. According to the test results, the test group 3 not only consumes more powder, but also has more granules. The use of the process of the present application can effectively improve the economy of the production process of aureomycin. In combination Figure 4 As can be seen from the material of each group, the test group 1 not only produces a large amount of powder, but also has uneven particle size, brittle particle texture, and still has the problem of bag sticking. The test group 2 has a moderate amount of powder, and the particle texture is slightly improved. Overall, the test group 3 has the best powder amount and better particle strength, and is not easy to break during production.

[0083] The above only describes the preferred embodiments of the present application. It should be noted that for those skilled in the art, without departing from the technical principles of the present application, a number of improvements and refinements can be made, which should also be considered within the protection scope of the present application.

Claims

1. A process for producing a chlortetracycline premix, characterized in that: The following steps are involved: S1: adding chlortetracycline fermentation broth to a composite carrier at a weight volume ratio of 7%, wherein the composite carrier is made of chlortetracycline powder and heavy calcium powder, the fermentation broth and the carrier are fully mixed, and then plate and frame filtration is performed to obtain a filter cake with a water content of 45% to 55%; S2: crushing the filter cake to obtain a wet material, adding chlortetracycline powder to the wet material and reducing the moisture content to below 40%; S3: adding not less than 5‰ by weight of sodium carboxymethyl cellulose to the wet material of S2 and mixing well; S4: Granulate the wet material of S3 with a granulator, control the sieve aperture of the granulator to be no higher than 3 mm, collect the wet granular granulation material; dry the wet granular granulation material in a fluidized bed, sieve the dried material to obtain 20-80 mesh material, crush and sieve the material above the 20 mesh sieve, and put the material below the 80 mesh sieve into S1 for use.

2. The process for producing chlortetracycline premix according to claim 1, wherein: In step S1, the composite carrier is prepared from chlortetracycline powder and heavy calcium powder in a weight ratio of (1-5): (2-6).

3. The process for producing chlortetracycline premix according to claim 2, wherein: The composite carrier in step S1 is prepared from chlortetracycline powder and heavy calcium powder in a weight ratio of (1-3): (4-6).

4. The process for producing chlortetracycline premix according to claim 3, wherein: The composite carrier in step S1 is prepared from chlortetracycline powder and heavy calcium powder in a weight ratio of 3:

4.

5. The process for producing chlortetracycline premix according to claim 1, wherein: In step S2, the moisture content of the wet material is reduced to 30% to 38%.

6. The process for producing chlortetracycline premix according to claim 5, characterized in that: In step S2, the moisture content of the wet material is reduced to 36%.

7. The process for producing chlortetracycline premix according to claim 1, characterized in that: The amount of sodium carboxymethyl cellulose added in step S3 is 5‰ to 9‰.

8. The process for producing chlortetracycline premix according to claim 1, wherein: The aperture of the granulator screen in step S4 is 1 to 3 mm.

9. The process for producing chlortetracycline premix according to claim 1, wherein: The titer of the chlortetracycline fermentation broth is 28500 U / mL.

10. A chlortetracycline premix, characterized in that: The chlortetracycline premix is ​​prepared by the production process according to any one of claims 1 to 9.

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