Background technology
Salinomycin is a monocarboxylic acid polyethers animal specific antibiotic; Most of gram positive bacterias and various coccidiosis there are stronger inhibition and killing action, are difficult for producing drug resistance and cross-resistance, drain rapidly; Residual quantity is extremely low, can be used for preventing and treating diarrhoea, growth promotion, raising survival rate.Salinomycin has the cation transport effect in cell, especially the affinity to potassium ion, sodium ion, rubidium ion is high especially, and these ion selectivities are flowed out outside films, causes ionic equilibrium to destroy, the osmotic pressure imbalance, cell expansion, be out of shape, break, disintegrate.
The method for preparing of Salinomycin pre-mixing agent comprises solvent extraction, spray drying method, plate-and-frame filtration method etc.Application number is that 93115177.5 Chinese patent discloses a kind of method of utilizing the Powdered feed grade Salinomycin Sodium of spray drying method for preparation; The Salinomycin fermentation liquid is heated through alkalization; After separating concentration, make excipient, adopt spray-dired method convection drying Salinomycin mycelium with calcium carbonate; Obtain the feed grade Salinomycin Sodium of different content, its finished product is the fawn uniform powder.This method is made Powdered Salinomycin Sodium, removes in the production process and very easily produces dust, influence the operative employee healthy outside, also progressively be eliminated along with the popularization of pellet.Application number is the method for preparing that 200410023920.1 Chinese patent discloses a kind of Salinomycin Sodium granule; Supernatant concentration is gone in Salinomycin fermentation liquid sedimentation after sterilization treatment; Add adjuvant and medicinal adhesive a-starch, methylol fiber sodium and sodium carboxymethyl cellulose in proportion; The adjustment pH value is an alkalescence, processes the dried granule of Salinomycin Sodium with the bed spray seasoning.Though this method can prepare the graininess Salinomycin Sodium by meeting the market requirement, complex procedures, the production cycle is long, and is all unfavorable to production cost and product quality.In addition, the content of the Salinomycin pre-mixing agent that prior art is prepared is generally 10% or 12%, and high-load Salinomycin pre-mixing agent can not reach requirement usually.
Summary of the invention
In view of this, the object of the present invention is to provide a kind of method for preparing of salinomycin particle premix, this method can reduce the influence of external additive, fast, stable, energy-conservation uniformity height and the high Salinomycin pre-mixing agent of content produced.
For realizing above-mentioned purpose, technical scheme of the present invention is:
The method for preparing of salinomycin particle premix may further comprise the steps:
A prepares alkaline broth: will tire is that the Salinomycin fermentation liquid of 60000~100000u/ml is regulated pH to 6.5~10.0 with alkali, alkaline broth;
B prepares the Salinomycin feed liquid: in step a gained alkaline broth, add the calcium carbonate that is equivalent to alkaline broth quality 0~25%, get the Salinomycin feed liquid;
C spray drying: step b gained Salinomycin feed liquid is processed granule with spray drying method, promptly get salinomycin particle premix.
Further, further comprising the steps of between said step a and the step b: as step a gained alkaline broth to be heated to 40~42 ℃ of insulations 4 hours earlier, to add sodium silicate solution and with acid for adjusting pH to 7~8, again according to the said adding calcium carbonate of step b;
Further, the mass concentration of said sodium silicate solution is 0.5%, and the addition of said sodium silicate solution is equivalent to 1~6% of alkaline broth volume.
Beneficial effect of the present invention is: this method is high with the salinomycin particle premix homogeneity and the stability of quick, energy-conservation mode of production preparation, and its content can be up to 31%; It is low at high-load salinomycin particle fat content that the present invention prepares, and then guaranteed quality of stability.
The specific embodiment
Below will carry out detailed description to the preferred embodiments of the present invention with reference to accompanying drawing.
Embodiment 1 content is the method for preparing of 16.5% salinomycin particle premix
The spawn culture of 1 Salinomycin
Select in the inclined-plane the plentiful single bacterium colony of outward appearance several, under aseptic condition, the bacterium colony spore is put into the 5ml sterilized water and shakes up.Evenly be applied to the method for scoring spore suspension and produce on the spore slant medium and place 30 ℃ of thermostatic chambers to cultivate 8 days, well-grown slant pore bottle is indicated strain number, on following bottle of date, preserve in 2~4 ℃ of refrigerators subsequent use.
2 fermenting and producing
Add 30ml water in every inclined-plane of sub-slant pore, carefully scrape spore and make it not carry any culture medium material, merge and pour in the aseptic bottle, pressure differential method is inoculated in the 500L first class seed pot then, and after 30 hours, mycelia polybrochate merogenesis mycelia is sturdy, does not have assorted bacterium.Abnormal smells from the patient is normal, and light yellow, PH7.0, Biomass are 22%; With its subcultivation to 3m
3In the secondary seed jar, after 10 hours, the growth mycelia is sturdy, and branch is few, and polybrochate does not have assorted bacterium PH7.0, and Biomass is 29%, and subcultivation is to 6m
3In the fermentation tank, at 35 ℃ of fermentation culture 268 hours, ventilation 1.3, pressure 0.05Mpa, moisturizing 800L, repairing 348L, logical alkali 50L; Putting a jar Salinomycin tires: 78000u/ml.
3 feed liquids are handled
Get above-mentioned fermentation liquid 500L, get in the storage tank, pH is transferred to 9.8, add calcium carbonate 120Kg, stir with caustic soda solution.
4 spray dryinges
Open spray drying device, when wind pushing temperature reaches 120 ℃ of left and right sides, open intake valve, close exhaust valve.Temperature is raised to 70 ℃ in tower, when temperature of outgoing air is 60 ℃, starts centrifuge.Open inlet valve then, a small amount of charging is also adjusted the feed liquid flow at any time, and when EAT rises to more than 140 ℃, temperature in the tower, temperature of outgoing air are stable, and atomizing is good, normal charging.Obtain Salinomycin Sodium granule semi-finished product 220Kg.
5. hybrid packed
To be transported to through the semi-finished product that are up to the standards after the spray drying in the mixer, through the mixer uniform mixing after 40 minutes, so that obtain the mixture of the even homogeneity of this product.The mass fraction of in time notifying reviewer's sampling inspection wherein to contain Salinomycin behind the mix homogeneously is 16.5%, and the product that is up to the standards can import packing into from mixer.
Embodiment 2 content are the method for preparing of 31% salinomycin particle premix
1. the spawn culture of Salinomycin
Select in the inclined-plane the plentiful single bacterium colony of outward appearance several, under aseptic condition, the bacterium colony spore is put into the 5ml sterilized water and shakes up.Evenly be applied to the method for scoring spore suspension and produce on the spore slant medium and place 30 ℃ of thermostatic chambers to cultivate 8 days, well-grown slant pore bottle is indicated strain number, on following bottle of date, preserve in 2~4 ℃ of refrigerators subsequent use.
2. fermenting and producing
Add 30ml water in every inclined-plane of sub-slant pore, carefully scrape spore and make it not carry any culture medium material, merge and pour in the aseptic bottle, pressure differential method is inoculated in the 500L first class seed pot then, and after 32 hours, mycelia polybrochate merogenesis mycelia is sturdy, does not have assorted bacterium.Abnormal smells from the patient is normal, and light yellow, PH7.0, Biomass are 24%; With its subcultivation to 3m
3In the secondary seed jar, after 9 hours, the growth mycelia is sturdy, and branch is few, and polybrochate does not have assorted bacterium PH7.0, and Biomass is 32%, and subcultivation is to 6m
3In the fermentation tank, at 33 ℃ of fermentation culture 288 hours, ventilation 1.3, pressure 0.05Mpa, moisturizing 900L, repairing 402L, logical alkali 78L; Putting a jar Salinomycin tires: 72000u/ml.
3 feed liquids are handled
Get above-mentioned 500L fermentation liquid, get in the storage tank, pH is transferred to 9.5 with sodium hydroxide solution; Fermentation liquid is heated to 40 degrees centigrade, is incubated 4 hours, adding mass concentration is 0.5% sodium silicate solution 30L; Transfer PH to 7.5 with hydrochloric acid, add calcium carbonate 20Kg, stir.
4 spray dryinges
Open spray drying device, when wind pushing temperature reaches 120 ℃ of left and right sides, open intake valve, close exhaust valve.Temperature is raised to 70 ℃ in tower, when temperature of outgoing air is 60 ℃, starts centrifuge.Open inlet valve then, a small amount of charging is also adjusted the feed liquid flow at any time, and when EAT rises to more than 140 ℃, temperature in the tower, temperature of outgoing air are stable, and atomizing is good, normal charging.Obtain salinomycin particle semi-finished product 110Kg.
5. hybrid packed
To be transported to through the semi-finished product that are up to the standards after the spray drying in the mixer, through the mixer uniform mixing after 40 minutes, so that obtain the mixture of the even homogeneity of this product.The mass fraction of in time notifying reviewer's sampling inspection wherein to contain Salinomycin behind the mix homogeneously is 31%, and the product that is up to the standards can import packing into from mixer.
In the method for preparing of above-mentioned salinomycin particle premix, the realization of consumption that can be through regulating calcium carbonate prepares the salinomycin particle premix of different content, wherein, when the consumption of calcium carbonate is 0, can prepare the highest salinomycin particle premix of content; When the higher salinomycin particle premix of preparation content; Usually can produce the too high problem of fat content; And then cause salinomycin particle in bulk and the unstable a series of problems of quality in the storage process, and can reach except that greasy purpose through adding sodium silicate solution.
Explanation is at last; Above embodiment is only unrestricted in order to technical scheme of the present invention to be described; Although through invention has been described with reference to the preferred embodiments of the present invention; But those of ordinary skill in the art should be appreciated that and can make various changes to it in form with on the details, and the spirit and scope of the present invention that do not depart from appended claims and limited.