CN105343010A - Preparation technology based on yield improvement of salinomycin granular preparation - Google Patents
Preparation technology based on yield improvement of salinomycin granular preparation Download PDFInfo
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- CN105343010A CN105343010A CN201510759012.7A CN201510759012A CN105343010A CN 105343010 A CN105343010 A CN 105343010A CN 201510759012 A CN201510759012 A CN 201510759012A CN 105343010 A CN105343010 A CN 105343010A
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- salinomycin
- fermentation liquid
- acid
- acid fermentation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
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- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Inorganic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a preparation technology based on yield improvement of salinomycin granular preparation. The preparation technology comprises the following steps: preparing acid fermentation liquor; adjusting the pH of salinomycin fermentation liquor to be 4.0-5.0 by adopting acid liquor; carrying out pretreatment on the acid fermentation liquor; carrying out heat preservation on the acid fermentation liquor after pH regulation at 60-65 DEG C for 3-4 h; adjusting the pH to be basic, and carrying out saponification to prepare salinomycin feed liquid; adding a certain amount of light calcium carbonate into the obtained acid fermentation liquor to prepare salinomycin feed liquid; carrying out spray drying; and carrying out spray drying on the prepared salinomycin feed liquid to prepare granules, thus obtaining the salinomycin granular preparation. According to the invention, the acid fermentation is adopted as the fermentation technology of salinomycin, the pH is adjusted to be basic, and then saponification is carried out, so that the layering speed of the fermentation liquor is accelerated, the layering time is shortened, the layering is complete, and the yield of salinomycin is improved.
Description
Technical field
The present invention relates to medical art, particularly, relating to the preparation technology based on improving salinomycin particle preparation yield.
Background technology
Salinomycin is the polyethers ionophore type animal specific antibiotic produced by streptomyces albus.Salinomycin particle preparation not only good anti-bacterial effect, low toxicity and low residue, production technology is simple, and raw material is easy to get and cheap, is one of veterinary drug of the most prospect that market is approved.
Salinomycin has stronger inhibitory action and killing action to most of gram positive bacteria and various coccidiosis, not easily produces drug resistance and cross-resistance, and rapidly, residual quantity is extremely low in excretion, can be used for preventing suffering from diarrhoea, promotes production, improves survival rate.Salinomycin has cation transport effect in cell, and especially to the affinity of potassium ion, sodium ion, rubidium ion, but these ion selectivities flow out outside film, cause ionic equilibrium to destroy, osmotic pressure imbalance, cell expansion, be out of shape, break, disintegrate.
Existing salinomycin particle preparation process due to Salinomycin fermentation liquor pretreatment step and spray step the unreasonable yield of salinomycin particle preparation that causes of process lower.
Summary of the invention
Technical problem to be solved by this invention is to provide the preparation technology based on improving salinomycin particle preparation yield, to overcome the low problem of yield that existing salinomycin particle preparation process causes.
The present invention's adopted technical scheme that solves the problem is: based on the preparation technology improving salinomycin particle preparation yield, comprise the following steps:
1) acid fermentation liquid, is prepared: Salinomycin fermentation liquid acid solution is regulated pH to 4.0 ~ 5.0;
2), the pretreatment of acid fermentation liquid: will the acid fermentation liquid of pH be mixed up 60 DEG C ~ 65 DEG C insulations 3 ~ 4 hours;
3), plate-and-frame filtration: to through step 2) add sodium hydroxide as saponifier in the acid fermentation liquid that obtains, add perlite, kieselguhr and precipitated calcium carbonate as filter aid, add alkali liquor and regulate pH to be 8.5 ~ 9.5, abundant saponification;
4) Salinomycin feed liquid, is prepared: make Salinomycin feed liquid to obtaining adding a certain amount of precipitated calcium carbonate in fermentation liquid after step 3) saponification;
5), spraying dry: adopt spray drying method to make granule the Salinomycin feed liquid prepared through step 4), obtain salinomycin particle preparation.
Existing salinomycin particle preparation process is all generally adopt base extraction for the fermentation process of fermentation liquid, cause the layered velocity of fermentation liquid slow, generally all want about 12h, and layering is not thorough and then cause the yield of Salinomycin low, fermentation technology to Salinomycin of the present invention adopts acid fermentation, after adopt regulate pH alkalize after carry out saponification, improve the speed of fermentation liquid layering, shorten the time of layering, and layering is thorough, improve the yield of Salinomycin, so, instant invention overcomes the problem that yield that existing salinomycin particle preparation process causes is low.
Further, the acid solution described in step 1) is sulphuric acid or phosphoric acid.
Further, the medicine valency of the Salinomycin fermentation liquid described in step 1) is 80000 ~ 100000u/ml.
Further, in step 4), the addition of precipitated calcium carbonate is 10% ~ 20% of acid fermentation liquid quality.
Further, step 2) described in alkali liquor be sodium carbonate.
To sum up, the invention has the beneficial effects as follows:
Fermentation technology to Salinomycin of the present invention adopts acid fermentation, after adopt regulate pH alkalize after carry out saponification, improves the speed of fermentation liquid layering, shorten the time of layering, and layering is thorough, improves the yield of Salinomycin.
Detailed description of the invention
Below in conjunction with embodiment, to the detailed description further of invention do, but embodiments of the present invention are not limited thereto.
Embodiment 1:
Based on the preparation technology improving salinomycin particle preparation yield, comprise the following steps:
1) acid fermentation liquid, is prepared: the Salinomycin fermentation liquid sulfur acid for adjusting pH to 4.0 by medicine valency being 80000u/ml;
2), the pretreatment of acid fermentation liquid: will the acid fermentation liquid of pH be mixed up 60 DEG C of insulations 3 hours;
3), plate-and-frame filtration: to through step 2) add sodium hydroxide as saponifier in the acid fermentation liquid that obtains, add perlite, kieselguhr and precipitated calcium carbonate as filter aid, add sodium carbonate and regulate pH to be 8.5, abundant saponification;
4), prepare Salinomycin feed liquid: make Salinomycin feed liquid to obtaining adding a certain amount of precipitated calcium carbonate in fermentation liquid after step 3) saponification, described precipitated calcium carbonate addition be 10% of acid fermentation liquid quality;
5), spraying dry: adopt spray drying method to make granule the Salinomycin feed liquid prepared through step 4), obtain salinomycin particle preparation.
Embodiment 2:
Based on the preparation technology improving salinomycin particle preparation yield, comprise the following steps:
1) acid fermentation liquid, is prepared: the Salinomycin fermentation liquid sulfur acid for adjusting pH to 4.5 by medicine valency being 90000u/ml;
2), the pretreatment of acid fermentation liquid: will the acid fermentation liquid of pH be mixed up 62 DEG C of insulations 3.5 hours;
3), plate-and-frame filtration: to through step 2) add sodium hydroxide as saponifier in the acid fermentation liquid that obtains, add perlite, kieselguhr and precipitated calcium carbonate as filter aid, add sodium carbonate and regulate pH to be 9.0, abundant saponification;
4), prepare Salinomycin feed liquid: make Salinomycin feed liquid to obtaining adding a certain amount of precipitated calcium carbonate in fermentation liquid after step 3) saponification, described precipitated calcium carbonate addition be 15% of acid fermentation liquid quality;
5), spraying dry: adopt spray drying method to make granule the Salinomycin feed liquid prepared through step 4), obtain salinomycin particle preparation.
Embodiment 3:
Based on the preparation technology improving salinomycin particle preparation yield, comprise the following steps:
1) acid fermentation liquid, is prepared: the Salinomycin fermentation liquid sulfur acid for adjusting pH to 5.0 by medicine valency being 100000u/ml;
2), the pretreatment of acid fermentation liquid: will the acid fermentation liquid of pH be mixed up 65 DEG C of insulations 4 hours;
3), plate-and-frame filtration: to through step 2) add sodium hydroxide as saponifier in the acid fermentation liquid that obtains, add perlite, kieselguhr and precipitated calcium carbonate as filter aid, add sodium carbonate and regulate pH to be 9.5, abundant saponification;
4), prepare Salinomycin feed liquid: make Salinomycin feed liquid to obtaining adding a certain amount of precipitated calcium carbonate in fermentation liquid after step 3) saponification, described precipitated calcium carbonate addition be 20% of acid fermentation liquid quality;
5), spraying dry: adopt spray drying method to make granule the Salinomycin feed liquid prepared through step 4), obtain salinomycin particle preparation.
As mentioned above, the present invention can be realized preferably.
Claims (5)
1., based on the preparation technology improving salinomycin particle preparation yield, it is characterized in that, comprise the following steps:
1) acid fermentation liquid, is prepared: Salinomycin fermentation liquid acid solution is regulated pH to 4.0 ~ 5.0;
2), the pretreatment of acid fermentation liquid: will the acid fermentation liquid of pH be mixed up 60 DEG C ~ 65 DEG C insulations 3 ~ 4 hours;
3), plate-and-frame filtration: to through step 2) add sodium hydroxide as saponifier in the acid fermentation liquid that obtains, add perlite, kieselguhr and precipitated calcium carbonate as filter aid, add alkali liquor and regulate pH to be 8.5 ~ 9.5, abundant saponification;
4) Salinomycin feed liquid, is prepared: make Salinomycin feed liquid to obtaining adding a certain amount of precipitated calcium carbonate in fermentation liquid after step 3) saponification;
5), spraying dry: adopt spray drying method to make granule the Salinomycin feed liquid prepared through step 4), obtain salinomycin particle preparation.
2. the preparation technology based on improving salinomycin particle preparation yield according to claim 1, it is characterized in that, the acid solution described in step 1) is sulphuric acid or phosphoric acid.
3. the preparation technology based on improving salinomycin particle preparation yield according to claim 1, it is characterized in that, the medicine valency of the Salinomycin fermentation liquid described in step 1) is 80000 ~ 100000u/ml.
4. the preparation technology based on improving salinomycin particle preparation yield according to claim 1, it is characterized in that, in step 4), the addition of precipitated calcium carbonate is 10% ~ 20% of acid fermentation liquid quality.
5. the preparation technology based on improving salinomycin particle preparation yield according to claim 1, is characterized in that, step 2) described in alkali liquor be sodium carbonate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510759012.7A CN105343010A (en) | 2015-11-10 | 2015-11-10 | Preparation technology based on yield improvement of salinomycin granular preparation |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201510759012.7A CN105343010A (en) | 2015-11-10 | 2015-11-10 | Preparation technology based on yield improvement of salinomycin granular preparation |
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| CN105343010A true CN105343010A (en) | 2016-02-24 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201510759012.7A Pending CN105343010A (en) | 2015-11-10 | 2015-11-10 | Preparation technology based on yield improvement of salinomycin granular preparation |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108484630A (en) * | 2018-03-30 | 2018-09-04 | 内蒙古拜克生物有限公司 | A kind of salinomycin method of purification |
-
2015
- 2015-11-10 CN CN201510759012.7A patent/CN105343010A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108484630A (en) * | 2018-03-30 | 2018-09-04 | 内蒙古拜克生物有限公司 | A kind of salinomycin method of purification |
| CN108484630B (en) * | 2018-03-30 | 2019-03-05 | 内蒙古拜克生物有限公司 | A kind of salinomycin method of purification |
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Application publication date: 20160224 |
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| WD01 | Invention patent application deemed withdrawn after publication |