CN103275154B - The preparation method of acetylisovaleryl tylosin salt-pepper noise particle - Google Patents
The preparation method of acetylisovaleryl tylosin salt-pepper noise particle Download PDFInfo
- Publication number
- CN103275154B CN103275154B CN201310265755.XA CN201310265755A CN103275154B CN 103275154 B CN103275154 B CN 103275154B CN 201310265755 A CN201310265755 A CN 201310265755A CN 103275154 B CN103275154 B CN 103275154B
- Authority
- CN
- China
- Prior art keywords
- acetylisovaleryl tylosin
- salt
- isopropylcarbinol
- preparation
- pepper noise
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Medicinal Preparation (AREA)
- Saccharide Compounds (AREA)
- Confectionery (AREA)
Abstract
The present invention relates to a kind of preparation method of acetylisovaleryl tylosin salt-pepper noise particle, first the powder of acetylisovaleryl tylosin salt is fully dissolved in ethyl acetate by the method, then under whipped state, 0 ~ 2 DEG C of temperature condition, slow dropping isopropylcarbinol mixes, mixing terminates to leave standstill afterwards, solid-liquid separation, drip washing and vacuum-drying.The present invention, by acetylisovaleryl tylosin salt is prepared into crystalline particle, replaces pulvis with crystal grain, because crystalline particle proportion is comparatively large, avoids dust pollution in packaging and use procedure; Sink under water in crystalline particle interpolation animal drinking water, better dispersed, dissolution rate is very fast, and content is higher, can directly add in animal-feed or animal drinking water, and the organic solvent of use can reclaim and again utilize, and has certain application prospect.
Description
Technical field
The invention belongs to technical field prepared by antibiotic product, particularly relate to a kind of preparation method of acetylisovaleryl tylosin salt-pepper noise particle.
Background technology
Acetylisovaleryl tylosin, also known as safe ten thousand rhzomorphs, is semi-synthetic through biological fermentation on tylosin basis and the special microbiotic of a kind of Macrolide poultry that is that obtain, produces the mutant strain that bacterial classification is 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, there is efficient, wide spectrum, not easily produce the features such as resistance, toxic side effect are little, become the good microbiotic preventing and treating acute respiratory system and gi system disease at present clinically, be with a wide range of applications.Common on 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, causes certain injury to operator's health, causes certain pollution to environment; Use acetylisovaleryl tylosin salt pulvis to add in feed or animal drinking-water in, pulvis proportion is less, swims on the water surface, and dissolve slowly, impact normally uses.Pre-mixture acetylisovaleryl tylosin salt is made by some enterprises or granule is sold, but will reduce its content in preparation process, affect drug effect.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of acetylisovaleryl tylosin salt-pepper noise particle, the method is by being prepared into crystalline particle by acetylisovaleryl tylosin salt, pulvis is replaced with crystal grain, because crystalline particle proportion is comparatively large, in packaging and use procedure, avoid dust pollution; Sink under water in crystalline particle interpolation animal drinking water, better dispersed, dissolution rate is very fast, and content is higher, can be directly used in animal drinking water additive.
The technical solution adopted in the present invention is as follows:
A kind of preparation method of acetylisovaleryl tylosin salt-pepper noise particle, it is characterized in that its processing step is: be first fully dissolved in ethyl acetate by the powder of acetylisovaleryl tylosin salt, then under whipped state, 0 ~ 2 DEG C of temperature condition, slow dropping isopropylcarbinol mixes, mixing terminates to leave standstill afterwards, solid-liquid separation, drip washing and vacuum-drying.
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 every 3 ~ 5 L ethyl acetate.
Above-mentioned mixing speed controls at 20 ~ 30r/min.
In above-mentioned mixing process, the consumption of isopropylcarbinol is 1 ~ 2 times of ethyl acetate volume, 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 the isopropylcarbinol drip washing crystalline particle 2 times of employing 0 ~ 2 DEG C, and the amount of each drip washing isopropylcarbinol used is 0.5 ~ 1 times of ethyl acetate volume.
Above-mentioned vacuum-drying adopts DoubletaperedVacuumdrier to realize, and its drying temperature controls at 50 ~ 60 DEG C, and vacuum degree control is at-0.08 ~-0.02MPa, and weight loss on drying stops vacuum-drying after 1%.
After above-mentioned solid-liquid separation, the mixed solvent of gained is at 68 ~ 72 DEG C, underpressure distillation under the condition of-0.02 ~-0.1MPa, reclaims and obtains vinyl acetic monomer and isopropylcarbinol.
Compared with prior art, advantage of the present invention:
(1) the present invention is compared with the pulvis of acetylisovaleryl tylosin salt, adopts crystallization mode, avoids the dust pollution of medicine, reduce the body harm of operator, decrease the pollution to environment.
(2) crystalline particle of acetylisovaleryl tylosin salt prepared of the present invention, no matter add feed to or add in animal drinking water, better dispersed, dissolution rate is very fast, and not easily conglomeration is easy to use.
(3) the present invention directly using acetylisovaleryl tylosin crystalline particle as additive, do not reduce its content, there is certain application prospect.
(4) this crystallization mode is adopted to produce acetylisovaleryl tylosin particle, crystallization yield > 98%.
(5) organic solvent after using is convenient to reclaim, and can reuse, and reduces production cost.
Embodiment
Be explained the present invention with example below, it should be understood that example is for illustration of the present invention instead of limitation of the present invention.Scope of the present invention and core content are determined according to claims.
embodiment 1
Weigh tartrate acetylisovaleryl tylosin powder 10kg, measure ethyl acetate 30L.Start stirring system, tartrate acetylisovaleryl tylosin is joined in ethyl acetate, is then cooled to 2 DEG C.Rotating speed controls at 20r/min.Under whipped state, slowly add isopropylcarbinol, isopropylcarbinol add-on is 30L, and rate of addition controls the 10%/min in total amount, and in whole mixing process, temperature controls all the time at 0 ~ 2 DEG C.Mixing terminates, and leaves standstill 30min, carries out solid-liquid separation.The solid obtained after the centrifugal isopropylcarbinol drip washing 2 times of 2 DEG C, first time drip washing consumption is 15L, and second time drip washing consumption is 15L.Start DoubletaperedVacuumdrier dry, drying temperature controls at 50 DEG C, and vacuum degree control is at-0.02MPa, and to weight loss on drying lower than 1%, obtain tartrate acetylisovaleryl tylosin crystalline particle 9.82kg, yield is 98.2%.Centrifugation gained mixed solvent is at 68 ~ 72 DEG C, and under the condition of-0.02 ~-0.1 MPa, solvent is reclaimed in underpressure distillation, is separated isopropylcarbinol and ethyl acetate.Solvent rate of recovery > 97%.
embodiment 2
Weigh tartrate acetylisovaleryl tylosin powder 10kg, measure ethyl acetate 40L.Start stirring system, tartrate acetylisovaleryl tylosin is joined in ethyl acetate, is then cooled to 1 DEG C.Rotating speed controls at 25r/min.Under whipped state, slowly add isopropylcarbinol, isopropylcarbinol add-on is 60L, and rate of addition controls the 10%/min in total amount, and in whole mixing process, temperature controls all the time at 0 ~ 2 DEG C.Mixing terminates, and leaves standstill 30min, carries out solid-liquid separation.The solid obtained after the centrifugal isopropylcarbinol drip washing 2 times of 1 DEG C, first time drip washing consumption is 30L, and second time drip washing consumption is 30L.Start DoubletaperedVacuumdrier dry, drying temperature controls at 55 DEG C, and vacuum degree control is at-0.02MPa, and to weight loss on drying lower than 1%, obtain tartrate acetylisovaleryl tylosin crystalline particle 9.84kg, yield is 98.4%.Centrifugation gained mixed solvent is at 68 ~ 72 DEG C, and under the condition of-0.02 ~-0.1 MPa, solvent is reclaimed in underpressure distillation, is separated isopropylcarbinol and ethyl acetate.Solvent rate of recovery > 97%.
embodiment 3
Weigh tartrate acetylisovaleryl tylosin powder 10kg, measure ethyl acetate 50L.Start stirring system, tartrate acetylisovaleryl tylosin is joined in ethyl acetate, is then cooled to 0 DEG C.Rotating speed controls at 30r/min.Under whipped state, slowly add isopropylcarbinol, isopropylcarbinol add-on is 100L, and rate of addition controls the 10%/min in total amount, and in whole mixing process, temperature controls all the time at 0 ~ 2 DEG C.Mixing terminates, and leaves standstill 30min, carries out solid-liquid separation.The solid obtained after the centrifugal isopropylcarbinol drip washing 2 times of 0 DEG C, first time drip washing consumption is 50L, and second time drip washing consumption is 50L.Start DoubletaperedVacuumdrier dry, drying temperature controls at 60 DEG C, and vacuum degree control is at-0.02MPa, and to weight loss on drying lower than 1%, obtain tartrate acetylisovaleryl tylosin crystalline particle 9.87kg, yield is 98.7%.Centrifugation gained mixed solvent is at 68 ~ 72 DEG C, and under the condition of-0.02 ~-0.1 MPa, solvent is reclaimed in underpressure distillation, is separated isopropylcarbinol and ethyl acetate.Solvent rate of recovery > 97%.
embodiment 4
Weigh phosphate isovaleryl tylosin powder 10kg, measure ethyl acetate 30L.Start stirring system, tartrate acetylisovaleryl tylosin is joined in ethyl acetate, is then cooled to 2 DEG C.Rotating speed controls at 20r/min.Under whipped state, slowly add isopropylcarbinol, isopropylcarbinol add-on is 30L, and rate of addition controls the 10%/min in total amount, and in whole mixing process, temperature controls all the time at 0 ~ 2 DEG C.Mixing terminates, and leaves standstill 30min, carries out solid-liquid separation.The solid obtained after the centrifugal isopropylcarbinol drip washing 2 times of 2 DEG C, first time drip washing consumption is 15L, and second time drip washing consumption is 15L.Start DoubletaperedVacuumdrier dry, drying temperature controls at 50 DEG C, and vacuum degree control is at-0.02MPa, and to weight loss on drying lower than 1%, obtain phosphate isovaleryl tylosin crystalline particle 9.83kg, yield is 98.3%.Centrifugation gained mixed solvent is at 68 ~ 72 DEG C, and under the condition of-0.02 ~-0.1 MPa, solvent is reclaimed in underpressure distillation, is separated isopropylcarbinol and ethyl acetate.Solvent rate of recovery > 97%.
embodiment 5
Weigh phosphate isovaleryl tylosin powder 10kg, measure ethyl acetate 40L.Start stirring system, tartrate acetylisovaleryl tylosin is joined in ethyl acetate, is then cooled to 1 DEG C.Rotating speed controls at 25r/min.Under whipped state, slowly add isopropylcarbinol, isopropylcarbinol add-on is 60L, and rate of addition controls the 10%/min in total amount, and in whole mixing process, temperature controls all the time at 0 ~ 2 DEG C.Mixing terminates, and leaves standstill 30min, carries out solid-liquid separation.The solid obtained after the centrifugal isopropylcarbinol drip washing 2 times of 1 DEG C, first time drip washing consumption is 30L, and second time drip washing consumption is 30L.Start DoubletaperedVacuumdrier dry, drying temperature controls at 55 DEG C, and vacuum degree control is at-0.04MPa, and to weight loss on drying lower than 1%, obtain tartrate acetylisovaleryl tylosin crystalline particle 9.82kg, yield is 98.2%.Centrifugation gained mixed solvent is at 68 ~ 72 DEG C, and under the condition of-0.02 ~-0.1 MPa, solvent is reclaimed in underpressure distillation, is separated isopropylcarbinol and ethyl acetate.Solvent rate of recovery > 97%.
embodiment 6
Weigh phosphate isovaleryl tylosin powder 10kg, measure ethyl acetate 50L.Start stirring system, tartrate acetylisovaleryl tylosin is joined in ethyl acetate, is then cooled to 0 DEG C.Rotating speed controls at 30r/min.Under whipped state, slowly add isopropylcarbinol, isopropylcarbinol add-on is 100L, and rate of addition controls the 10%/min in total amount, and in whole mixing process, temperature controls all the time at 0 ~ 2 DEG C.Mixing terminates, and leaves standstill 30min, carries out solid-liquid separation.The solid obtained after the centrifugal isopropylcarbinol drip washing 2 times of 0 DEG C, first time drip washing consumption is 50L, and second time drip washing consumption is 50L.Start DoubletaperedVacuumdrier dry, drying temperature controls at 60 DEG C, and vacuum degree control is at-0.08MPa, and to weight loss on drying lower than 1%, obtain tartrate acetylisovaleryl tylosin crystalline particle 9.85kg, yield is 98.5%.Centrifugation gained mixed solvent is at 68 ~ 72 DEG C, and under the condition of-0.02 ~-0.1 MPa, solvent is reclaimed in underpressure distillation, is separated isopropylcarbinol and ethyl acetate.Solvent rate of recovery > 97%.
Claims (7)
1. the preparation method of an acetylisovaleryl tylosin salt-pepper noise particle, it is characterized in that its processing step is: the powder of acetylisovaleryl tylosin salt is fully dissolved in ethyl acetate by the amount ratio first adding 1 kg acetylisovaleryl tylosin salt according to every 3 ~ 5 L ethyl acetate, then under whipped state, 0 ~ 2 DEG C of temperature condition, slow dropping isopropylcarbinol mixes, wherein the consumption of isopropylcarbinol is 1 ~ 2 times of ethyl acetate volume, and rate of addition is the 10%/min of total amount; Mixing terminates to leave standstill afterwards, solid-liquid separation, drip washing and vacuum-drying;
Above-mentioned drip washing refers to the isopropylcarbinol drip washing crystalline particle 2 times of employing 0 ~ 2 DEG C, and the amount of each drip washing isopropylcarbinol used is 0.5 ~ 1 times of ethyl acetate volume.
2., according to the preparation method of acetylisovaleryl tylosin salt-pepper noise particle according to claim 1, it is characterized in that described acetylisovaleryl tylosin salt is its tartrate or phosphoric acid salt.
3., according to the preparation method of acetylisovaleryl tylosin salt-pepper noise particle according to claim 1, it is characterized in that above-mentioned mixing speed controls at 20 ~ 30r/min.
4., according to the preparation method of acetylisovaleryl tylosin salt-pepper noise particle according to claim 1, it is characterized in that above-mentioned time of repose is 30 ~ 40min.
5., according to the preparation method of acetylisovaleryl tylosin salt-pepper noise particle according to claim 1, it is characterized in that above-mentioned solid-liquid separation adopts centrifugation.
6. according to the preparation method of acetylisovaleryl tylosin salt-pepper noise particle according to claim 1, it is characterized in that above-mentioned vacuum-drying adopts DoubletaperedVacuumdrier to realize, its drying temperature controls at 50 ~ 60 DEG C, vacuum degree control is at-0.08 ~-0.02MPa, and weight loss on drying stops vacuum-drying after 1%.
7. according to the preparation method of the acetylisovaleryl tylosin salt-pepper noise particle described in claim 1 or 5, it is characterized in that the mixed solvent of gained after above-mentioned solid-liquid separation is at 68 ~ 72 DEG C, underpressure distillation under the condition of-0.02 ~-0.1MPa, reclaims and obtains vinyl acetic monomer and isopropylcarbinol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310265755.XA CN103275154B (en) | 2013-06-28 | 2013-06-28 | The preparation method of acetylisovaleryl tylosin salt-pepper noise particle |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310265755.XA CN103275154B (en) | 2013-06-28 | 2013-06-28 | The preparation method of acetylisovaleryl tylosin salt-pepper noise particle |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103275154A CN103275154A (en) | 2013-09-04 |
| CN103275154B true CN103275154B (en) | 2015-08-12 |
Family
ID=49057796
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310265755.XA Active CN103275154B (en) | 2013-06-28 | 2013-06-28 | The preparation method of acetylisovaleryl tylosin salt-pepper noise particle |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103275154B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| CN107936074B (en) * | 2017-12-26 | 2021-09-28 | 湖北回盛生物科技有限公司 | Purification method of tulathromycin |
| CN108358979B (en) * | 2018-05-22 | 2020-08-25 | 中牧实业股份有限公司 | Purification method of tulathromycin |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4362881A (en) * | 1980-07-02 | 1982-12-07 | Eli Lilly And Company | Tylactone |
| US6664240B2 (en) * | 2001-11-15 | 2003-12-16 | Enanta Pharmaceuticals, Inc. | Tylosin derivatives having antibacterial activity |
| CN101381756B (en) * | 2007-09-07 | 2012-01-25 | 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 |
| CN102659882B (en) * | 2012-05-11 | 2015-04-22 | 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
Also Published As
| Publication number | Publication date |
|---|---|
| CN103275154A (en) | 2013-09-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103275155A (en) | Preparation method of tylosin phosphate or tartrate crystal | |
| CN103275154B (en) | The preparation method of acetylisovaleryl tylosin salt-pepper noise particle | |
| CN106345414A (en) | Magnetic core-shell nanocomposite as well as preparation method and application thereof | |
| CN104856972A (en) | Amoxicillin capsules and preparation method thereof | |
| CN101961427A (en) | Method for extracting polysaccharide and polyphenol of oil-tea camellia husk | |
| CN102659882B (en) | Method for extracting tartaric acid acetylisovaleryl tylosion | |
| CN107523093B (en) | Preparation method of carotenoid pigment-clay composite product | |
| CN104530087B (en) | A kind of Cefazolin sodium novel crystal form and preparation method thereof | |
| CN104666249A (en) | Ceflazidime powder preparation for injection | |
| CN102659818A (en) | Hydrochloric acid cefotiam crystalline compound, preparation method thereof and medicine combination containing compound | |
| CN104961749B (en) | A kind of infant industry crystallization method of Cefuroxime sodium and preparation thereof | |
| CN103099295A (en) | Fructus kochiae natural preservative and preparation method thereof | |
| CN103288904B (en) | Preparation method of tilmicosin phosphate crystal | |
| CN103012536B (en) | Sodium fusidate crystallization method | |
| CN101235025B (en) | Method for preparing theaflavin | |
| CN104447795A (en) | Cefadroxil compound and pharmaceutical composition comprising same | |
| CN101502496B (en) | Method for preparing norfloxacin capsule | |
| CN104231044A (en) | Process for purifying nosiheptide by passing through column | |
| CN104543413B (en) | A kind of preparation method of avilamycin pre-mixing agent | |
| CN103319632A (en) | Preparation method of powder rubber | |
| CN102675476A (en) | Production method for soluble starch | |
| CN101723957A (en) | Method for preparing ampicillin sodium salt | |
| CN103127058A (en) | Moxidectin preparation and preparing method thereof | |
| CN103288694B (en) | Preparation method of pleuromutilin synthetic derivate salt crystal | |
| CN101942009B (en) | Compound medicament for separating crude proteins from monosodium glutamate-fermented waste liquor and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |