CN106928193B - Preparation meets the method for the esomeprazole magnesium trihydrate of standards of pharmacopoeia - Google Patents
Preparation meets the method for the esomeprazole magnesium trihydrate of standards of pharmacopoeia Download PDFInfo
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- CN106928193B CN106928193B CN201710137186.9A CN201710137186A CN106928193B CN 106928193 B CN106928193 B CN 106928193B CN 201710137186 A CN201710137186 A CN 201710137186A CN 106928193 B CN106928193 B CN 106928193B
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- esomeprazole
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Abstract
The invention discloses a kind of prepare to meet the method for the esomeprazole magnesium trihydrate of standards of pharmacopoeia, which comprises the steps of: S101, at room temperature, esomeprazole potassium is soluble in water, then stirring puts into active carbon, by diatomite filter bed after stirring at room temperature, it is washed with water；Wet cake obtained by step S101 is transferred in another reactor, is slowly added to magnesium chloride solution by S102, at room temperature, then puts into EDTA solution, is centrifuged, is washed with water after stirring, drying of spinning, discharging；S103, step S102 resulting material is transferred in drying equipment, is heated to 60-65 DEG C and drying 3-4 hours, is cooled to room temperature rear discharging.This method is easy to operate, and the color and solubility of product are qualified, conducive to commercially producing.
Description
Technical field
The present invention relates to medicine synthesising process, the esomeprazole magnesium three for meeting standards of pharmacopoeia more particularly, to preparation is hydrated
The method of object.
Background technique
Patent WO9854171A2, which discloses to be reacted by esomeprazole potassium with magnesium sulfate, prepares esomeprazole magnesium, then
The method of preparation esomeprazole magnesium trihydrate is reacted with water.Patent WO2004046134A2, WO2004089935A1,
WO2007031845A2 discloses the method for directly reacting preparation esomeprazole magnesium trihydrate with water by esomeprazole magnesium.
Patent CN105111188A, which is disclosed, is dissolved in esomeprazole magnesium after C1-C3 alkanol through active carbon drainage, then anti-with water again
The method that esomeprazole magnesium trihydrate should be prepared.
By the description of patent WO9854171A1, WO2004046134A2, WO2004089935A1 and WO2007031845A2
Esomeprazole magnesium trihydrate is prepared, because there are crystallinity using the three hydration magnesium salts directly at salt, obtained in water
The problems such as difference, filtration difficulty, drying time is long, some products will could even be dried using the methods of microwave drying, be unfavorable for
Commodity production.Esomeprazole magnesium trihydrate color by the description preparation of patent CN105111188A is partially dark, finished product
Solubility is unqualified, does not meet the regulation of European Pharmacopoeia and United States Pharmacopeia.
Summary of the invention
The purpose of the present invention is to solve the above-mentioned problems, provides a kind of esomeprazole for preparing and meeting standards of pharmacopoeia
The method of magnesium trihydrate, it is intended to which commodity production color and solubility meet the esomeprazole of European Pharmacopoeia and United States Pharmacopeia
Magnesium trihydrate.
To achieve the goals above, the present invention adopts the following technical scheme: a kind of prepare the Esso beauty for meeting standards of pharmacopoeia
The method for drawing azoles magnesium trihydrate, includes the following steps:
S101, at room temperature, esomeprazole potassium is soluble in water, then stirring puts into active carbon, leads to after stirring at room temperature
Diatomite filter bed is crossed, is washed with water；
Wet cake obtained by step S101 is transferred in another reactor, it is molten to be slowly added to magnesium chloride by S102, at room temperature
Then liquid puts into EDTA solution, is centrifuged, is washed with water after stirring, drying of spinning, discharging；
S103, step S102 resulting material is transferred in drying equipment, is heated to 60-65 DEG C and dried 3-4 hours, it is cold
But to discharging after room temperature.
Preferably: in step S101, stirring put into active carbon after 10-20 minutes.
Preferably: in step S101, passing through diatomite filter bed after stirring 25-35 minutes at room temperature
Preferably: in step S102, stirring is centrifuged after 25-35 minutes.
Preferably: in step S102, spin is 60 minutes dry.
Preferably: in step S101, the w/v of esomeprazole potassium and water is 0.18-0.22KG/L.
Preferably: in step S101, by weight, activated carbon addition is the 0.018- of esomeprazole potassium weight
0.023 times.
Preferably: in step S102, according to poidometer, magnesium chloride weight is esomeprazole potassium weight in magnesium chloride solution
0.24-0.26 times.
Preferably: in step S102, according to poidometer, the ratio between EDTA solution additive amount and esomeprazole potassium additive amount are
0.0068-0.0072。
Compared with prior art, it is easy to operate that the invention has the following beneficial effects: this method, the color and dissolution of product
Degree is qualified, conducive to commercially producing.
Specific embodiment
A method of the esomeprazole magnesium trihydrate for meeting standards of pharmacopoeia is prepared, is included the following steps:
S101, at room temperature, esomeprazole potassium is soluble in water, then stirring puts into active carbon, leads to after stirring at room temperature
Diatomite filter bed is crossed, is washed with water；
Wet cake obtained by step S101 is transferred in another reactor (reaction kettle), is slowly added to chlorine by S102, at room temperature
Change magnesium solution, then puts into EDTA solution, be centrifuged, be washed with water after stirring, drying of spinning, discharging；
S103, step S102 resulting material is transferred in drying equipment (carriage-type drying case), is heated to 60-65 DEG C and does
It is 3-4 hours dry, it is cooled to room temperature rear discharging.
In step S101, stirring put into active carbon, preferably 15 minutes after 10-20 minutes.
In step S101, at room temperature stir 25-35 minute after pass through diatomite filter bed, preferably 30 minutes.
In step S102, stirring is centrifuged after 25-35 minutes, and preferably 30 minutes.
In step S102, spin is 55-65 minutes, preferably 60 minutes dry.
In step S101, the w/v of esomeprazole potassium and water is 0.18-0.22KG/L, preferably 0.2KG/L.
In step S101, by weight, activated carbon addition is 0.018-0.023 times of esomeprazole potassium weight.
In step S102, according to poidometer, magnesium chloride weight is the 0.24- of esomeprazole potassium weight in magnesium chloride solution
0.26 times, preferably 0.25 times.
In step S102, according to poidometer, the ratio between EDTA solution additive amount and esomeprazole potassium additive amount are 0.0068-
0.0072。
The present invention prepares esomeprazole magnesium trihydrate by intermediate of esomeprazole potassium.In order to make esomeprazole
The coloration compliance of magnesium trihydrate has carried out pre-treatment to esomeprazole potassium, i.e., esomeprazole potassium has been dissolved in water, then thrown
Enter after active carbon is stirred at room temperature 30 minutes and is filtered by diatomite filter bed；Meanwhile in order to make esomeprazole magnesium trihydrate
Solubility meets regulation, with (ethylenediamine tetra-acetic acid) EDTA solution is added in the reacting of water.
Embodiment: (1) checking the cleanliness of reaction kettle,
(2) investment 1300L-1480L water is to reaction kettle,
(3) stirring is lower puts into 260-296kg esomeprazole potassium,
(4) stirring makes to be completely dissolved at room temperature,
(5) active carbon suspension (6kg active carbon+6L water) is put into,
(6) it stirs 10-15 minutes,
(7) it is filtered by diatomite filter bed, with 260-296L water washing, collects filtrate,
(8) 65-74kg magnesium chloride being put into aqueous bucket, stirring makes to be completely dissolved, it filters,
(9) at room temperature, in the esomeprazole potassium filter that above-mentioned magnesium chloride solution is added to charcoal treated in 20 minutes
In liquid,
(10) investment EDTA solution (2KG) is to reaction kettle,
(11) stir about 30 minutes,
(12) it is centrifuged, with 100L water washing, dry discharging after sixty minutes of spinning,
(13) material of above-mentioned steps is transferred in carriage-type drying case, is warming up to 60-65 DEG C, drying 3-4 hours.
Product colour obtained and solubility are as shown in Table 1 according to the method described above:
Table one:
The foregoing is merely the preferred embodiment of the present invention, protection scope of the present invention is not limited in above-mentioned embodiment party
Formula, all technical solutions for belonging to the principle of the invention all belong to the scope of protection of the present invention.For those skilled in the art and
Speech, several improvement carried out without departing from the principles of the present invention, these improvement also should be regarded as protection model of the invention
It encloses.
Claims (1)
1. a kind of prepare the method for meeting the esomeprazole magnesium trihydrate of standards of pharmacopoeia, which is characterized in that including walking as follows
It is rapid:
S101, at room temperature, esomeprazole potassium is soluble in water, then stirring puts into active carbon, passes through silicon after stirring at room temperature
Diatomaceous earth filter bed, is washed with water；
Wet cake obtained by step S101 is transferred in another reactor, is slowly added to magnesium chloride solution, so by S102, at room temperature
EDTA solution is put into afterwards, is centrifuged, is washed with water after stirring, drying of spinning, discharging；
S103, step S102 resulting material is transferred in drying equipment, is heated to 60-65 DEG C and 3-4 hours dry, cooling
Discharging after to room temperature；
In step S101, stirring put into active carbon after 10-20 minutes；
In step S101, pass through diatomite filter bed after stirring 25-35 minutes at room temperature；
In step S102, stirring is centrifuged after 25-35 minutes；
In step S102, spin is 60 minutes dry；
In step S101, the w/v of esomeprazole potassium and water is 0.18-0.22KG/L,
In step S101, by weight, activated carbon addition is 0.018-0.023 times of esomeprazole potassium weight；
In step S102, according to poidometer, magnesium chloride weight is the 0.24- of esomeprazole potassium weight in magnesium chloride solution
0.26 times；
In step S102, according to poidometer, the ratio between EDTA solution additive amount and esomeprazole potassium additive amount are 0.0068-
0.0072。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710137186.9A CN106928193B (en) | 2017-03-09 | 2017-03-09 | Preparation meets the method for the esomeprazole magnesium trihydrate of standards of pharmacopoeia |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710137186.9A CN106928193B (en) | 2017-03-09 | 2017-03-09 | Preparation meets the method for the esomeprazole magnesium trihydrate of standards of pharmacopoeia |
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| CN106928193A CN106928193A (en) | 2017-07-07 |
| CN106928193B true CN106928193B (en) | 2018-12-11 |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108409714A (en) * | 2018-03-29 | 2018-08-17 | 成都通德药业有限公司 | The preparation method of esomeprazole, esomeprazole salt and esomeprazole magnesium |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004089935A1 (en) * | 2003-04-10 | 2004-10-21 | Hetero Drugs Limitd | Novel crystalline forms of s-omeprazole magnesium |
| CN102993184A (en) * | 2013-01-08 | 2013-03-27 | 湖南方盛制药股份有限公司 | Esomeprazole and preparation method of magnesium trihydrate of esomeprazole |
| CN104356114B (en) * | 2014-11-17 | 2017-02-22 | 江苏中邦制药有限公司 | Preparation method of esomeprazole magnesium trihydrate |
| CN104610227A (en) * | 2015-01-08 | 2015-05-13 | 浙江亚太药业股份有限公司 | High-pressure hydrothermal preparation method for esomeprazole magnesium polymorphic compound |
| CN105418588A (en) * | 2016-01-17 | 2016-03-23 | 青岛辰达生物科技有限公司 | Method for preparing high-purity esomeprazole magnesium trihydrate |
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