CN106928193A - 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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- CN106928193A CN106928193A CN201710137186.9A CN201710137186A CN106928193A CN 106928193 A CN106928193 A CN 106928193A CN 201710137186 A CN201710137186 A CN 201710137186A CN 106928193 A CN106928193 A CN 106928193A
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- esomeprazole
- pharmacopoeia
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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
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a kind of method of the esomeprazole magnesium trihydrate for preparing and meeting standards of pharmacopoeia, it is characterised in that comprise the following steps：S101, at room temperature, esomeprazole potassium is soluble in water, stirring, then puts into activated carbon, by diatomite filter bed after stirring at room temperature, washes with water；S102, at room temperature, step S101 gained wet cakes are transferred in another reactor, are slowly added to magnesium chloride solution, then put into EDTA solution, are centrifuged after stirring, are washed with water, spin drying, discharging；S103, step S102 resulting materials are transferred in drying equipment, are heated to 60 65 DEG C and dry 34 hours, be cooled to discharging after room temperature.The method is easy to operate, and the color of product is qualified with solubility, beneficial to commercially producing.
Description
Technical field
The present invention relates to medicine synthesising process, the hydration of esomeprazole magnesium three of standards of pharmacopoeia is met more particularly, to preparation
The method of thing.
Background technology
Patent WO9854171A2 is disclosed and is prepared esomeprazole magnesium by esomeprazole potassium and sulfuric acid reactive magnesium, then
The method for preparing esomeprazole magnesium trihydrate with water reaction.Patent WO2004046134A2, WO2004089935A1,
WO2007031845A2 discloses the method for preparing esomeprazole magnesium trihydrate by esomeprazole magnesium and water direct reaction.
Patent CN105111188A is disclosed and esomeprazole magnesium is dissolved in after C1-C3 alkanols through activated 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 using directly into salt in water, the three hydration magnesium salts for obtaining have crystallinity
Difference, filtration difficulty, the problems such as drying time is long, some products will could even be dried using methods such as microwave dryings, be unfavorable for
Commodity production.The esomeprazole magnesium trihydrate color prepared by the description of patent CN105111188A is partially dark, finished product
Solubility is unqualified, does not meet the regulation of European Pharmacopoeia and American Pharmacopeia.
The content of the invention
The purpose of the present invention is exactly to solve the above problems, there is provided a kind of to prepare the esomeprazole for 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 American Pharmacopeia
Magnesium trihydrate.
To achieve these goals, the present invention is adopted the following technical scheme that：It is a kind of to prepare the Esso U.S. for meeting standards of pharmacopoeia
The method for drawing azoles magnesium trihydrate, comprises the following steps：
S101, at room temperature, esomeprazole potassium is soluble in water, stirring, then puts into activated carbon, leads to after stirring at room temperature
Diatomite filter bed is crossed, is washed with water；
S102, at room temperature, step S101 gained wet cakes are transferred in another reactor, are slowly added to magnesium chloride molten
Liquid, then puts into EDTA solution, is centrifuged after stirring, washes with water, spin drying, discharging；
S103, step S102 resulting materials are transferred in drying equipment, are heated to 60-65 DEG C and dry 3-4 hours, it is cold
But to discharging after room temperature.
Preferably：In step S101, stirring puts into activated carbon after 10-20 minutes.
Preferably：In step S101, diatomite filter bed is passed through 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 dried 60 minutes.
Preferably：In step S101, esomeprazole potassium is 0.18-0.22KG/L with the w/v of water.
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 weight meter, magnesium chloride weight is esomeprazole potassium weight in magnesium chloride solution
0.24-0.26 times.
Preferably：In step S102, according to weight meter, the ratio between EDTA solution addition and esomeprazole potassium addition are
0.0068-0.0072。
Compared with prior art, the present invention has the advantages that：The method is easy to operate, color and the dissolving of product
Degree is qualified, beneficial to commercially producing.
Specific embodiment
A kind of method for preparing the esomeprazole magnesium trihydrate for meeting standards of pharmacopoeia, comprises the following steps：
S101, at room temperature, esomeprazole potassium is soluble in water, stirring, then puts into activated carbon, leads to after stirring at room temperature
Diatomite filter bed is crossed, is washed with water；
S102, at room temperature, step S101 gained wet cakes are transferred in another reactor (reactor), are slowly added to chlorine
Change magnesium solution, then put into EDTA solution, be centrifuged after stirring, wash with water, spin drying, discharging；
S103, step S102 resulting materials are transferred in drying equipment (carriage-type drying case), are heated to 60-65 DEG C and do
It is dry 3-4 hours, it is cooled to discharging after room temperature.
In step S101, stirring puts into activated carbon, preferably 15 minutes after 10-20 minutes.
In step S101, by diatomite filter bed after stirring 25-35 minutes at room temperature, preferably 30 minutes.
In step S102, stirring is centrifuged after 25-35 minutes, preferably 30 minutes.
In step S102, spin dries 55-65 minutes, preferably 60 minutes.
In step S101, esomeprazole potassium is 0.18-0.22KG/L, preferably 0.2KG/L with the w/v of water.
In step S101, by weight, activated carbon addition is 0.018-0.023 times of esomeprazole potassium weight.
In step S102, according to weight meter, 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 weight meter, the ratio between EDTA solution addition and esomeprazole potassium addition are 0.0068-
0.0072。
The present invention prepares esomeprazole magnesium trihydrate by intermediate of esomeprazole potassium.In order that esomeprazole
The coloration compliance of magnesium trihydrate, pre-treatment has been carried out to esomeprazole potassium, will esomeprazole potassium be dissolved in water, then throw
Enter after activated carbon is stirred at room temperature 30 minutes and filtered by diatomite filter bed；Meanwhile, in order that esomeprazole magnesium trihydrate
Solubility meets regulation, and (ethylenediamine tetra-acetic acid) EDTA solution is added in the reaction with water.
Embodiment：(1) cleanliness factor of reactor is checked,
(2) 1300L-1480L water is put into reactor,
(3) lower input 260-296kg esomeprazole potassium is stirred,
(4) stirring makes to be completely dissolved at room temperature,
(5) input activated carbon suspension (6kg activated carbon+6L water),
(6) stir 10-15 minutes,
(7) filtered by diatomite filter bed, use 260-296L water washings, collect filtrate,
(8) by the aqueous bucket of 65-74kg magnesium chlorides input, stirring makes to be completely dissolved, and filters,
(9) at room temperature, in the esomeprazole potassium filter that above-mentioned magnesium chloride solution is added charcoal treated in 20 minutes
In liquid,
(10) EDTA solution (2KG) is put into reactor,
(11) stir about 30 minutes,
(12) it is centrifuged, discharging after using 100L water washings, spin to dry 60 minutes,
(13) material of above-mentioned steps is transferred in carriage-type drying case, is warming up to 60-65 DEG C, dried 3-4 hours.
Obtained product colour and solubility is as shown in Table 1 according to the method described above：
Table one：
The preferred embodiment of the present invention is the foregoing is only, protection scope of the present invention is not limited in above-mentioned embodiment party
Formula, every technical scheme for belonging to the principle of the invention belongs to protection scope of the present invention.For those skilled in the art
Speech, some improvement carried out on the premise of principle of the invention is not departed from, these improvement also should be regarded as protection model of the invention
Enclose.
Claims (9)
1. a kind of method for preparing the esomeprazole magnesium trihydrate for meeting standards of pharmacopoeia, it is characterised in that including following step
Suddenly：
S101, at room temperature, esomeprazole potassium is soluble in water, stirring, then puts into activated carbon, and silicon is passed through after stirring at room temperature
Diatomaceous earth filter bed, washes with water；
S102, at room temperature, step S101 gained wet cakes are transferred in another reactor, are slowly added to magnesium chloride solution, so
EDTA solution is put into afterwards, is centrifuged after stirring, wash with water, spin drying, discharging；
S103, step S102 resulting materials are transferred in drying equipment, are heated to 60-65 DEG C and dry 3-4 hours, be cooled to
Discharging after room temperature.
2. the method that preparation according to claim 1 meets the esomeprazole magnesium trihydrate of standards of pharmacopoeia, its feature
It is：In step S101, stirring puts into activated carbon after 10-20 minutes.
3. the method that preparation according to claim 1 meets the esomeprazole magnesium trihydrate of standards of pharmacopoeia, its feature
It is：In step S101, diatomite filter bed is passed through after stirring 25-35 minutes at room temperature.
4. the method that preparation according to claim 1 meets the esomeprazole magnesium trihydrate of standards of pharmacopoeia, its feature
It is：In step S102, stirring is centrifuged after 25-35 minutes.
5. the method that preparation according to claim 1 meets the esomeprazole magnesium trihydrate of standards of pharmacopoeia, its feature
It is：In step S102, spin is dried 60 minutes.
6. the method that preparation according to claim 1 meets the esomeprazole magnesium trihydrate of standards of pharmacopoeia, its feature
It is：In step S101, esomeprazole potassium is 0.18-0.22KG/L with the w/v of water.
7. the method that preparation according to claim 1 meets the esomeprazole magnesium trihydrate of standards of pharmacopoeia, its feature
It is：In step S101, by weight, activated carbon addition is 0.018-0.023 times of esomeprazole potassium weight.
8. the method that preparation according to claim 1 meets the esomeprazole magnesium trihydrate of standards of pharmacopoeia, its feature
It is：In step S102, according to weight meter, magnesium chloride weight is the 0.24- of esomeprazole potassium weight in magnesium chloride solution
0.26 times.
9. the method that preparation according to claim 1 meets the esomeprazole magnesium trihydrate of standards of pharmacopoeia, its feature
It is：In step S102, according to weight meter, the ratio between EDTA solution addition and esomeprazole potassium addition are 0.0068-
0.0072。
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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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| 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 true CN106928193A (en) | 2017-07-07 |
| CN106928193B CN106928193B (en) | 2018-12-11 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
Citations (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 |
| CN104356114A (en) * | 2014-11-17 | 2015-02-18 | 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 |
-
2017
- 2017-03-09 CN CN201710137186.9A patent/CN106928193B/en active Active
Patent Citations (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 |
| CN104356114A (en) * | 2014-11-17 | 2015-02-18 | 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 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
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| CN106928193B (en) | 2018-12-11 |
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