CN105566425A - Method for refining prednisolone - Google Patents
Method for refining prednisolone Download PDFInfo
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- CN105566425A CN105566425A CN201610037548.2A CN201610037548A CN105566425A CN 105566425 A CN105566425 A CN 105566425A CN 201610037548 A CN201610037548 A CN 201610037548A CN 105566425 A CN105566425 A CN 105566425A
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- Prior art keywords
- prednisolone
- crude product
- purification
- refined soln
- organic solvent
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
- C07J5/0046—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa
- C07J5/0053—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond substituted in position 17 alfa not substituted in position 16
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a method for refining prednisolone. The method includes the steps that crude prednisolone with the content of 96%-98% serves as a raw material, a mixed solution of an organic solvent and water serves as a refining solution, and the crude prednisolone is put into the refining solution, and is heated and dissolved under the stirring condition; then cooling, crystallizing and filtering are carried out, and the high-purity prednisolone with the content of 99.10% or above is obtained. By means of the method, the product is high in content and yield. The reaction condition is mild, and operation is easy. The adopted refining solution is easy to obtain and low in cost. The method is suitable for large-scale production of a factory, and production cost is reduced.
Description
Technical field
The present invention relates to biomedicine, particularly relate to a kind of process for purification of prednisolone.
Background technology
Because the difference that synthesis technique and synthesis condition control, cause the prednisolone impurity of each manufacturer production at present varied, content is different.Traditional is refining, adopts one or several pure organic solvents such as methyl alcohol, methylene dichloride, ethyl acetate as refined soln more.Because the structure of the hydrocortisone in impurity and prednisolone is difference one 1, the double bond of 2, polarity is very close, use traditional process for purification, hydrocortisone content can only be down to 1% ~ 0.5%, for high-level prednisolone, then take to sacrifice yield, recrystallization method for several times.This operation, yield is low, and cost is high.
Summary of the invention
Object of the present invention, exactly in order to solve the problem, provides a kind of process for purification of novel prednisolone.
In order to achieve the above object, present invention employs following technical scheme: a kind of process for purification of prednisolone, be that 96% ~ 98% crude product prednisolone is for raw material with content, using the mixed solution of organic solvent and water as refined soln, crude product prednisolone is put in refined soln, under agitation heating for dissolving; Then cooling, crystallization, filtration, namely obtains the high purity prednisolone of content more than 99.10%.
Described organic solvent is selected from one or more in methyl alcohol, methylene dichloride, ethyl acetate, acetone, sherwood oil.
In described refined soln, the volume ratio of organic solvent and water is 1:9 ~ 2:3; The ratio of the volume milliliter number of refined soln and the weight grams of crude product prednisolone is 10:1 ~ 1:2.
Described heating for dissolving is under agitation that to be heated to refined soln be boiling state, and maintains 20 ~ 40 minutes and all dissolve to crude product prednisolone.
Described cooling, crystallization are after closing and stirring, and naturally let cool or water-bath cools, and are cooled to 0 ~-20 DEG C, place 8 ~ 10 hours, allow the abundant crystallization of prednisolone.
The present invention utilizes different in organic solvent and solubleness in the mixing solutions that water is formed of prednisolone and various impurity, purification prednisolone.Change the crystal formation of prednisolone simultaneously, become aciculiform from Polygons, be more conducive to purifying.
Beneficial effect of the present invention is as follows:
1, content is high, yield is high
Produce crude product prednisolone for raw material with Shandong, Henan, Zhejiang, with the inventive method operation (content in crude product is refined for twice at 96% ~ 98% primary purification, 91% ~ 96%), detect according to national standard, HPLC result is as shown in table 1:
Table 1
| Table-prednisolone % | Impurity-1% | Prednisone % | Impurity-2% | Prednisolone % | Hydrocortisone % | Dehydrogenation-RS% | |
| Sample 1 | 0.08 | 0.05 | 0.11 | 0.04 | 99.50 | 0.14 | 0.08 |
| Sample 2 | 0.10 | 0.05 | 0.14 | 0.04 | 99.38 | 0.20 | 0.09 |
| Sample 3 | 0.08 | 0.06 | 0.11 | 0.03 | 99.47 | 0.12 | 0.04 |
From table 1, adopt method of the present invention, comparatively conventional methanol is refined, and yield improves about 10%.
2, reaction conditions is gentle, simple to operate.
3, refined soln used is easy to get, and cheap.Very easily be applicable to plant sizeization to produce, reduce production cost.
Embodiment
Below by way of specific embodiment, technical scheme of the present invention is further described.
Embodiment 1:
Configure a certain amount of refined soln, organic solvent adopts methyl alcohol, and the volume of methyl alcohol and water is 1:9; Drop into a certain amount of crude product prednisolone, the ratio of the volume milliliter number of refined soln and the weight grams of crude product prednisolone is 10:1; Open and stir, system being warmed up to refined soln is boiling state, and maintain 20 minutes, crude product prednisolone all dissolves; Cool to 25 DEG C, close and stir, then cool to-5 DEG C, low temperature crystallization 10 hours, filter, dry, namely obtain a kind of high purity prednisolone of the present invention.
Embodiment 2:
Configure a certain amount of refined soln, organic solvent adopts methylene dichloride, and the volume of methylene dichloride and water is 1:3; Drop into a certain amount of crude product prednisolone, the ratio of the volume milliliter number of refined soln and the weight grams of crude product prednisolone is 1:2; Open and stir, system being warmed up to refined soln is boiling state, and maintain 30 minutes, crude product prednisolone all dissolves; Cool to 25 DEG C, close and stir, then cool to-2 DEG C, low temperature crystallization 9 hours, filter, dry, namely obtain a kind of high purity prednisolone of the present invention.
Embodiment 3:
Configure a certain amount of refined soln, organic solvent adopts ethyl acetate, and the volume of ethyl acetate and water is 2:3; Drop into a certain amount of crude product prednisolone, the ratio of the volume milliliter number of refined soln and the weight grams of crude product prednisolone is 2:1; Open and stir, system being warmed up to refined soln is boiling state, and maintain 40 minutes, crude product prednisolone all dissolves; Cool to 25 DEG C, close and stir, cool to-8 DEG C, low temperature crystallization 7 hours, filter, dry, namely obtain a kind of high purity prednisolone of the present invention.
Embodiment 4:
Configure a certain amount of refined soln, organic solvent adopts the mixture of ethyl acetate and acetone, and the volume of organic solvent and water is 1:5; Drop into a certain amount of crude product prednisolone, the ratio of the volume milliliter number of refined soln and the weight grams of crude product prednisolone is 5:9; Open and stir, system being warmed up to refined soln is boiling state, and maintain 40 minutes, crude product prednisolone all dissolves; Cool to 25 DEG C, close and stir, cool to-20 DEG C, low temperature crystallization 8 hours, filter, dry, namely obtain a kind of high purity prednisolone of the present invention.
Claims (5)
1. the process for purification of a prednisolone, it is characterized in that, with content be 96% ~ 98% crude product prednisolone for raw material, using the mixed solution of organic solvent and water as refined soln, crude product prednisolone is put in refined soln, under agitation heating for dissolving; Then cooling, crystallization, filtration, namely obtains the high purity prednisolone of content more than 99.10%.
2. the process for purification of prednisolone according to claim 1, is characterized in that: described organic solvent is selected from one or more in methyl alcohol, methylene dichloride, ethyl acetate, acetone, sherwood oil.
3. the process for purification of prednisolone according to claim 1, is characterized in that: in described refined soln, and the volume ratio of organic solvent and water is 1:9 ~ 2:3; The ratio of the volume milliliter number of refined soln and the weight grams of crude product prednisolone is 10:1 ~ 1:2.
4. the process for purification of prednisolone according to claim 1, is characterized in that: described heating for dissolving under agitation, is that to be heated to refined soln be boiling state, and maintains 20 ~ 40 minutes and all dissolve to crude product prednisolone.
5. the process for purification of prednisolone according to claim 1, is characterized in that: described cooling, crystallization, is after closing and stirring, and naturally lets cool or water-bath cools, and is cooled to 0 ~-20 DEG C, places 8 ~ 10 hours, allows the abundant crystallization of prednisolone.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610037548.2A CN105566425A (en) | 2016-01-20 | 2016-01-20 | Method for refining prednisolone |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610037548.2A CN105566425A (en) | 2016-01-20 | 2016-01-20 | Method for refining prednisolone |
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| Publication Number | Publication Date |
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| CN105566425A true CN105566425A (en) | 2016-05-11 |
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| CN201610037548.2A Pending CN105566425A (en) | 2016-01-20 | 2016-01-20 | Method for refining prednisolone |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113754713A (en) * | 2021-09-28 | 2021-12-07 | 丽江映华生物药业有限公司 | Method for decoloring and refining prednisone acetate |
| CN113801183A (en) * | 2021-09-13 | 2021-12-17 | 丽江映华生物药业有限公司 | Prednisolone refining method |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101397324A (en) * | 2007-09-29 | 2009-04-01 | 天津药业研究院有限公司 | Preparation of metacortandralone and derivatives thereof |
| CN103387595A (en) * | 2013-08-12 | 2013-11-13 | 李竞 | Method for preparing prednisolone |
| CN104610406A (en) * | 2013-11-05 | 2015-05-13 | 河南利华制药有限公司 | Prednisolone refining technology |
-
2016
- 2016-01-20 CN CN201610037548.2A patent/CN105566425A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101397324A (en) * | 2007-09-29 | 2009-04-01 | 天津药业研究院有限公司 | Preparation of metacortandralone and derivatives thereof |
| CN103387595A (en) * | 2013-08-12 | 2013-11-13 | 李竞 | Method for preparing prednisolone |
| CN104610406A (en) * | 2013-11-05 | 2015-05-13 | 河南利华制药有限公司 | Prednisolone refining technology |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113801183A (en) * | 2021-09-13 | 2021-12-17 | 丽江映华生物药业有限公司 | Prednisolone refining method |
| CN113754713A (en) * | 2021-09-28 | 2021-12-07 | 丽江映华生物药业有限公司 | Method for decoloring and refining prednisone acetate |
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Application publication date: 20160511 |
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