CN103275154A - Preparation method of crystalline particles of acetyl isovaleryl tylosin salt - Google Patents
Preparation method of crystalline particles of acetyl isovaleryl tylosin salt Download PDFInfo
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- CN103275154A CN103275154A CN201310265755XA CN201310265755A CN103275154A CN 103275154 A CN103275154 A CN 103275154A CN 201310265755X A CN201310265755X A CN 201310265755XA CN 201310265755 A CN201310265755 A CN 201310265755A CN 103275154 A CN103275154 A CN 103275154A
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Abstract
The invention relates to a preparation method of crystalline particles of acetyl isovaleryl tylosin salt. The method comprises the steps of sufficiently dissolving powder of the acetyl isovaleryl tylosin salt in ethyl acetate, slowly and dropwise adding isobutanol for mixing in a stirring state and at 0-2 DEG C, standing after the mixing, conducting solid-liquid separation, eluting, and conducting vacuum drying. According to the preparation method, the acetyl isovaleryl tylosin salt is prepared into the crystalline particles to replace powder; the specific gravity of the crystalline particles is greater, so that dust pollution is avoided in packaging and using processes; the crystalline particles are added to animal drinking water to sink into the water bottom, are better in dispersity, higher in dissolving speed and higher in content, and can be directly added to animal feed or the animal drinking water; a used organic solvent can be recovered and recycled; and the preparation method has a certain application prospect.
Description
Technical field
The invention belongs to the technical field of antibiotic product preparation, particularly relate to a kind of preparation method of acetylisovaleryl tylosin salt crystalline particle.
Background technology
Acetylisovaleryl tylosin claims safe ten thousand rhzomorphs again, is semi-synthetic through biological fermentation and a kind of Macrolide fowl that obtain is raiseeed special-purpose microbiotic on the tylosin basis, and producing bacterial classification is the mutant strain of heat-resisting streptomycete, belongs to a kind of actinomycetes.As a kind of novel macrolide antibiotic, overcome the deficiency of many Macrocyclolactone lactone kind medicines, characteristics such as having efficient, wide spectrum, be difficult for producing resistance, toxic side effect is little, become and prevent and treat the good microbiotic of acute respiratory system and gi system disease clinically at present, be with a wide range of applications.Common on the market is the salt of acetylisovaleryl tylosin.
At present, domestic production producer adopts spray-dired mode to prepare acetylisovaleryl tylosin salt, obtains pressed powder.Pulvis produces a large amount of dust in wrapping process, operator's health is caused certain injury, and environment is caused certain pollution; Use acetylisovaleryl tylosin salt pulvis adds in the feed or in the drinking-water of animal, pulvis proportion is less, swims on the water surface, and dissolving slowly influences normally use.Acetylisovaleryl tylosin salt is made pre-mixture in some enterprises or granule is sold, but will reduce its content in the preparation process, influence drug effect.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of acetylisovaleryl tylosin salt crystalline particle, this method is by being prepared into crystalline particle with acetylisovaleryl tylosin salt, replace pulvis with crystal grain, because crystalline particle proportion is bigger, avoid dust pollution in packing and the use; Sink under water in the crystalline particle interpolation animal drinking water, better dispersed, dissolution rate is very fast, and content is higher, can be directly used in the animal drinking water additive.
The technical solution adopted in the present invention is as follows:
A kind of preparation method of acetylisovaleryl tylosin salt crystalline particle, it is characterized in that its processing step is: at first the powder with acetylisovaleryl tylosin salt fully is dissolved in the ethyl acetate, then under whipped state, 0～2 ℃ of temperature condition, slowly drip isopropylcarbinol and mix, mix leave standstill after finishing, solid-liquid separation, drip washing and vacuum-drying gets final product.
Described acetylisovaleryl tylosin salt is its tartrate or phosphoric acid salt.
The dissolving of above-mentioned acetylisovaleryl tylosin salt adds 1 kg acetylisovaleryl tylosin salt meter according to per 3～5 L ethyl acetate.
Above-mentioned mixing speed control is at 20～30r/min.
The consumption of isopropylcarbinol is 1～2 times of ethyl acetate volume in the above-mentioned mixing process, and rate of addition is the 10%/min of total amount.
Above-mentioned time of repose is 30～40min.
Above-mentioned solid-liquid separation adopts centrifugation.
Above-mentioned drip washing refers to adopt 0～2 ℃ isopropylcarbinol drip washing crystalline particle 2 times, and the amount of each used isopropylcarbinol of drip washing is 0.5～1 times of ethyl acetate volume.
Above-mentioned vacuum-drying adopts DoubletaperedVacuumdrier to realize, its drying temperature control is at 50～60 ℃, vacuum degree control-0.08～-0.02MPa, stop vacuum-drying after weight loss on drying is lower than 1%.
The mixed solvent of gained is at 68～72 ℃ after the above-mentioned solid-liquid separation ,-0.02～-condition of 0.1MPa under underpressure distillation, reclaim and obtain vinyl acetic monomer and isopropylcarbinol.
Compared with prior art, advantage of the present invention:
(1) the present invention compares with the pulvis of acetylisovaleryl tylosin salt, adopts crystallization mode, has avoided the dust pollution of medicine, has reduced operator's health harm, has reduced the pollution to environment.
(2) no matter the crystalline particle of the acetylisovaleryl tylosin salt of the present invention preparation adds feed to or adds in the animal drinking water, and better dispersed, dissolution rate is very fast, is difficult for conglomeration, and is easy to use.
(3) the present invention directly with the acetylisovaleryl tylosin crystalline particle as additive, do not reduce its content, have certain application prospect.
(4) adopt this crystallization mode to produce acetylisovaleryl tylosin particle, crystallization yield＞98%.
(5) organic solvent after the use is convenient to reclaim, and can reuse, and reduces production costs.
Embodiment
With example the present invention is described below, is it should be understood that example is for explanation the present invention rather than limitation of the present invention.Scope of the present invention and core content are determined according to claims.
Embodiment 1
Weighing tartrate acetylisovaleryl tylosin powder 10kg is measured ethyl acetate 30L.Start stirring system, the tartrate acetylisovaleryl tylosin is joined in the ethyl acetate, be cooled to 2 ℃ then.Rotating speed control is at 20r/min.Slowly add isopropylcarbinol under whipped state, the isopropylcarbinol add-on is 30L, and rate of addition control is at the 10%/min of total amount, and temperature is controlled all the time at 0～2 ℃ in the whole mixing process.Mix and finish, leave standstill 30min, carry out solid-liquid separation.The solid that obtains after centrifugal is with 2 ℃ isopropylcarbinol drip washing 2 times, and the consumption of drip washing for the first time is 15L, and the consumption of drip washing for the second time is 15L.Start the DoubletaperedVacuumdrier drying, drying temperature is controlled at 50 ℃, and vacuum degree control is at-0.02MPa, is lower than 1% to weight loss on drying, obtains tartrate acetylisovaleryl tylosin crystalline particle 9.82kg, and yield is 98.2%.Centrifugation gained mixed solvent is at 68～72 ℃, and solvent is reclaimed in underpressure distillation under the condition of-0.02～-0.1 MPa, separates isopropylcarbinol and ethyl acetate.The solvent rate of recovery＞97%.
Embodiment 2
Weighing tartrate acetylisovaleryl tylosin powder 10kg is measured ethyl acetate 40L.Start stirring system, the tartrate acetylisovaleryl tylosin is joined in the ethyl acetate, be cooled to 1 ℃ then.Rotating speed control is at 25r/min.Slowly add isopropylcarbinol under whipped state, the isopropylcarbinol add-on is 60L, and rate of addition control is at the 10%/min of total amount, and temperature is controlled all the time at 0～2 ℃ in the whole mixing process.Mix and finish, leave standstill 30min, carry out solid-liquid separation.The solid that obtains after centrifugal is with 1 ℃ isopropylcarbinol drip washing 2 times, and the consumption of drip washing for the first time is 30L, and the consumption of drip washing for the second time is 30L.Start the DoubletaperedVacuumdrier drying, drying temperature is controlled at 55 ℃, and vacuum degree control is at-0.02MPa, is lower than 1% to weight loss on drying, obtains tartrate acetylisovaleryl tylosin crystalline particle 9.84kg, and yield is 98.4%.Centrifugation gained mixed solvent is at 68～72 ℃, and solvent is reclaimed in underpressure distillation under the condition of-0.02～-0.1 MPa, separates isopropylcarbinol and ethyl acetate.The solvent rate of recovery＞97%.
Embodiment 3
Weighing tartrate acetylisovaleryl tylosin powder 10kg is measured ethyl acetate 50L.Start stirring system, the tartrate acetylisovaleryl tylosin is joined in the ethyl acetate, be cooled to 0 ℃ then.Rotating speed control is at 30r/min.Slowly add isopropylcarbinol under whipped state, the isopropylcarbinol add-on is 100L, and rate of addition control is at the 10%/min of total amount, and temperature is controlled all the time at 0～2 ℃ in the whole mixing process.Mix and finish, leave standstill 30min, carry out solid-liquid separation.The solid that obtains after centrifugal is with 0 ℃ isopropylcarbinol drip washing 2 times, and the consumption of drip washing for the first time is 50L, and the consumption of drip washing for the second time is 50L.Start the DoubletaperedVacuumdrier drying, drying temperature is controlled at 60 ℃, and vacuum degree control is at-0.02MPa, is lower than 1% to weight loss on drying, obtains tartrate acetylisovaleryl tylosin crystalline particle 9.87kg, and yield is 98.7%.Centrifugation gained mixed solvent is at 68～72 ℃, and solvent is reclaimed in underpressure distillation under the condition of-0.02～-0.1 MPa, separates isopropylcarbinol and ethyl acetate.The solvent rate of recovery＞97%.
Embodiment 4
Weighing phosphoric acid acetylisovaleryl tylosin powder 10kg is measured ethyl acetate 30L.Start stirring system, the tartrate acetylisovaleryl tylosin is joined in the ethyl acetate, be cooled to 2 ℃ then.Rotating speed control is at 20r/min.Slowly add isopropylcarbinol under whipped state, the isopropylcarbinol add-on is 30L, and rate of addition control is at the 10%/min of total amount, and temperature is controlled all the time at 0～2 ℃ in the whole mixing process.Mix and finish, leave standstill 30min, carry out solid-liquid separation.The solid that obtains after centrifugal is with 2 ℃ isopropylcarbinol drip washing 2 times, and the consumption of drip washing for the first time is 15L, and the consumption of drip washing for the second time is 15L.Start the DoubletaperedVacuumdrier drying, drying temperature is controlled at 50 ℃, and vacuum degree control is at-0.02MPa, is lower than 1% to weight loss on drying, obtains phosphoric acid acetylisovaleryl tylosin crystalline particle 9.83kg, and yield is 98.3%.Centrifugation gained mixed solvent is at 68～72 ℃, and solvent is reclaimed in underpressure distillation under the condition of-0.02～-0.1 MPa, separates isopropylcarbinol and ethyl acetate.The solvent rate of recovery＞97%.
Embodiment 5
Weighing phosphoric acid acetylisovaleryl tylosin powder 10kg is measured ethyl acetate 40L.Start stirring system, the tartrate acetylisovaleryl tylosin is joined in the ethyl acetate, be cooled to 1 ℃ then.Rotating speed control is at 25r/min.Slowly add isopropylcarbinol under whipped state, the isopropylcarbinol add-on is 60L, and rate of addition control is at the 10%/min of total amount, and temperature is controlled all the time at 0～2 ℃ in the whole mixing process.Mix and finish, leave standstill 30min, carry out solid-liquid separation.The solid that obtains after centrifugal is with 1 ℃ isopropylcarbinol drip washing 2 times, and the consumption of drip washing for the first time is 30L, and the consumption of drip washing for the second time is 30L.Start the DoubletaperedVacuumdrier drying, drying temperature is controlled at 55 ℃, and vacuum degree control is at-0.04MPa, is lower than 1% to weight loss on drying, obtains tartrate acetylisovaleryl tylosin crystalline particle 9.82kg, and yield is 98.2%.Centrifugation gained mixed solvent is at 68～72 ℃, and solvent is reclaimed in underpressure distillation under the condition of-0.02～-0.1 MPa, separates isopropylcarbinol and ethyl acetate.The solvent rate of recovery＞97%.
Embodiment 6
Weighing phosphoric acid acetylisovaleryl tylosin powder 10kg is measured ethyl acetate 50L.Start stirring system, the tartrate acetylisovaleryl tylosin is joined in the ethyl acetate, be cooled to 0 ℃ then.Rotating speed control is at 30r/min.Slowly add isopropylcarbinol under whipped state, the isopropylcarbinol add-on is 100L, and rate of addition control is at the 10%/min of total amount, and temperature is controlled all the time at 0～2 ℃ in the whole mixing process.Mix and finish, leave standstill 30min, carry out solid-liquid separation.The solid that obtains after centrifugal is with 0 ℃ isopropylcarbinol drip washing 2 times, and the consumption of drip washing for the first time is 50L, and the consumption of drip washing for the second time is 50L.Start the DoubletaperedVacuumdrier drying, drying temperature is controlled at 60 ℃, and vacuum degree control is at-0.08MPa, is lower than 1% to weight loss on drying, obtains tartrate acetylisovaleryl tylosin crystalline particle 9.85kg, and yield is 98.5%.Centrifugation gained mixed solvent is at 68～72 ℃, and solvent is reclaimed in underpressure distillation under the condition of-0.02～-0.1 MPa, separates isopropylcarbinol and ethyl acetate.The solvent rate of recovery＞97%.
Claims (10)
1. the preparation method of an acetylisovaleryl tylosin salt crystalline particle, it is characterized in that its processing step is: at first the powder with acetylisovaleryl tylosin salt fully is dissolved in the ethyl acetate, then under whipped state, 0～2 ℃ of temperature condition, slowly drip isopropylcarbinol and mix, mix leave standstill after finishing, solid-liquid separation, drip washing and vacuum-drying gets final product.
2. according to the preparation method of the described acetylisovaleryl tylosin salt of claim 1 crystalline particle, it is characterized in that described acetylisovaleryl tylosin salt is its tartrate or phosphoric acid salt.
3. according to the preparation method of claim 1 or 2 described acetylisovaleryl tylosin salt crystalline particles, it is characterized in that the dissolving of above-mentioned acetylisovaleryl tylosin salt adds 1 kg acetylisovaleryl tylosin salt meter according to per 3～5 L ethyl acetate.
4. according to the preparation method of the described acetylisovaleryl tylosin salt of claim 1 crystalline particle, it is characterized in that above-mentioned mixing speed control is at 20～30r/min.
5. according to the preparation method of the described acetylisovaleryl tylosin salt of claim 1 crystalline particle, the consumption that it is characterized in that isopropylcarbinol in the above-mentioned mixing process is 1～2 times of ethyl acetate volume, and rate of addition is the 10%/min of total amount.
6. according to the preparation method of the described acetylisovaleryl tylosin salt of claim 1 crystalline particle, it is characterized in that above-mentioned time of repose is 30～40min.
7. according to the preparation method of the described acetylisovaleryl tylosin salt of claim 1 crystalline particle, it is characterized in that above-mentioned solid-liquid separation adopts centrifugation.
8. according to the preparation method of the described acetylisovaleryl tylosin salt of claim 1 crystalline particle, it is characterized in that above-mentioned drip washing refers to adopt 0～2 ℃ isopropylcarbinol drip washing crystalline particle 2 times, the amount of each used isopropylcarbinol of drip washing is 0.5～1 times of ethyl acetate volume.
9. according to the preparation method of the described acetylisovaleryl tylosin salt of claim 1 crystalline particle, it is characterized in that the realization of above-mentioned vacuum-drying employing DoubletaperedVacuumdrier, its drying temperature control is at 50～60 ℃, vacuum degree control-0.08～-0.02MPa, stop vacuum-drying after weight loss on drying is lower than 1%.
10. according to the preparation method of claim 1 or 7 described acetylisovaleryl tylosin salt crystalline particles, it is characterized in that the mixed solvent of gained after the above-mentioned solid-liquid separation is at 68～72 ℃,-0.02～-condition of 0.1MPa under underpressure distillation, reclaim and obtain vinyl acetic monomer and isopropylcarbinol.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103923140A (en) * | 2014-04-14 | 2014-07-16 | 宁夏泰瑞制药股份有限公司 | Preparation method of acetylisovaleryltylosin tartrate |
| CN107936074A (en) * | 2017-12-26 | 2018-04-20 | 湖北回盛生物科技有限公司 | A kind of purification process of safe ten thousand rhzomorph |
| CN108358979A (en) * | 2018-05-22 | 2018-08-03 | 中牧实业股份有限公司 | The purification process of safe ten thousand rhzomorphs |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4362881A (en) * | 1980-07-02 | 1982-12-07 | Eli Lilly And Company | Tylactone |
| WO2003043642A1 (en) * | 2001-11-15 | 2003-05-30 | Enanta Pharmaceuticals Inc. | Novel tylosin derivatives having antibacterial activity |
| CN101381756A (en) * | 2007-09-07 | 2009-03-11 | 中牧实业股份有限公司 | Purification method of super tylosin |
| CN101531693A (en) * | 2008-03-13 | 2009-09-16 | 迈德金生物技术（北京）有限公司 | Method for extracting acetylisovaleryl tylosin |
| CN102659882A (en) * | 2012-05-11 | 2012-09-12 | 湖北泱盛生物科技有限公司 | Method for extracting tartaric acid acetylisovaleryl tylosion |
-
2013
- 2013-06-28 CN CN201310265755.XA patent/CN103275154B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4362881A (en) * | 1980-07-02 | 1982-12-07 | Eli Lilly And Company | Tylactone |
| WO2003043642A1 (en) * | 2001-11-15 | 2003-05-30 | Enanta Pharmaceuticals Inc. | Novel tylosin derivatives having antibacterial activity |
| CN101381756A (en) * | 2007-09-07 | 2009-03-11 | 中牧实业股份有限公司 | Purification method of super tylosin |
| CN101531693A (en) * | 2008-03-13 | 2009-09-16 | 迈德金生物技术（北京）有限公司 | Method for extracting acetylisovaleryl tylosin |
| CN102659882A (en) * | 2012-05-11 | 2012-09-12 | 湖北泱盛生物科技有限公司 | Method for extracting tartaric acid acetylisovaleryl tylosion |
Non-Patent Citations (2)
| Title |
|---|
| 孙汉文，等: "《高分子化学实验》", 30 April 2012 * |
| 王金玲，等: "乙酰异戊酰泰乐菌素的合成", 《湖北农业科学》 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103923140A (en) * | 2014-04-14 | 2014-07-16 | 宁夏泰瑞制药股份有限公司 | Preparation method of acetylisovaleryltylosin tartrate |
| CN103923140B (en) * | 2014-04-14 | 2016-06-15 | 宁夏泰瑞制药股份有限公司 | The preparation method of a kind of tartrate acetylisovaleryl tylosin |
| CN107936074A (en) * | 2017-12-26 | 2018-04-20 | 湖北回盛生物科技有限公司 | A kind of purification process of safe ten thousand rhzomorph |
| CN107936074B (en) * | 2017-12-26 | 2021-09-28 | 湖北回盛生物科技有限公司 | Purification method of tulathromycin |
| CN108358979A (en) * | 2018-05-22 | 2018-08-03 | 中牧实业股份有限公司 | The purification process of safe ten thousand rhzomorphs |
| CN108358979B (en) * | 2018-05-22 | 2020-08-25 | 中牧实业股份有限公司 | Purification method of tulathromycin |
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