CN109265442A - A kind of refining methd of bulk pharmaceutical chemicals Lansoprazole - Google Patents
A kind of refining methd of bulk pharmaceutical chemicals Lansoprazole Download PDFInfo
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- CN109265442A CN109265442A CN201811189736.2A CN201811189736A CN109265442A CN 109265442 A CN109265442 A CN 109265442A CN 201811189736 A CN201811189736 A CN 201811189736A CN 109265442 A CN109265442 A CN 109265442A
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- lansoprazole
- pharmaceutical chemicals
- bulk pharmaceutical
- alkali
- alcohol
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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)
Abstract
The invention discloses a kind of refining methds of bulk pharmaceutical chemicals Lansoprazole, specific step is as follows: by the wet crude product of Lansoprazole, alcohol solution and alkali are added in reaction kettle by a certain percentage, stirring is warming up to dissolution, active carbon is added, decolourize 10~30min, filters pressing is to crystallizing tank, filtrate is cooled to 20 DEG C or less, it is slowly added to acid, stirring and crystallizing, filtering, filter cake is washed with alcohol solution and aqueous alkali respectively, collect filter cake, filter cake is added in purified water or aqueous alkali, agitator treating, filtering, filter cake is washed with aqueous alkali, obtain the wet fine work of Lansoprazole, forced air drying, until water content detection≤0.5%, obtain bulk pharmaceutical chemicals Lansoprazole.Operation of the present invention is simple, it is easily enlarged production, purification gained bulk pharmaceutical chemicals Lansoprazole is white crystalline powder, content is greater than 99.9%, list is miscellaneous to be not higher than 0.2%, and always miscellaneous to be not higher than 0.3%, residue on ignition is not higher than 0.1%, good product quality is much better than the quality standard of Chinese Pharmacopoeia two middle bulk pharmaceutical chemicals Lansoprazoles.
Description
Technical field
The invention belongs to bulk pharmaceutical chemicals Lansoprazole production technical fields, and in particular to a kind of purification of bulk pharmaceutical chemicals Lansoprazole
Method.
Background technique
Lansoprazole (lansoprazole), chemical name 2- [[[3- methyl -4-(2,2,2- trifluoro ethoxies) -2- pyridine
Base] methyl] sulfinyl] -1H- benzimidazole, white or off-white color crystalline powder, it is odorless, it meets light and air is perishable, it is main
It is used in the diseases such as gastric ulcer, duodenal ulcer.The Lansoprazole long period is sudden and violent in existing Lansoprazole subtractive process
Be exposed in air, and Lansoprazole meet light and air it is unstable, degradation apt to deteriorate so that purification after Lansoprazole in impurity
Content is high, and product quality is bad.
Summary of the invention
The purpose of the invention is to overcome the deficiencies in the prior art, and provide a kind of good product quality, easy to operate, easy
In the refining methd of the bulk pharmaceutical chemicals Lansoprazole of expanding production, Lansoprazole degradation apt to deteriorate in subtractive process can be solved,
The problem of increasing impurity content in product.
The object of the present invention is achieved like this: a kind of refining methd of bulk pharmaceutical chemicals Lansoprazole includes the following steps:
Step A: the wet crude product of Lansoprazole, alcohol solution and alkali are added in reaction kettle by a certain percentage, and stirring is warming up to molten
Active carbon is added in solution, and decolourize 10~30min, and filters pressing to crystallizing tank, wherein the wet crude product of Lansoprazole is by 2- chloromethyl -3- methyl -
4-(2,2,2- trifluoro ethoxy) pyridine hydrochloride and 2-mercaptobenzimidazole be made through condensation reaction and oxidation reaction；
Step B: the filtrate that step A is obtained in crystallizing tank is cooled to 20 DEG C hereinafter, being slowly added to acid, stirring and crystallizing filters, filter
Cake is washed with alcohol solution and aqueous alkali respectively, collects filter cake；
Step C: the obtained filter cake of step B being added in purified water or aqueous alkali, agitator treating, filtering, filter cake buck
Solution washing, obtains the wet fine work of Lansoprazole；
Step D: the wet fine work of the Lansoprazole that step C is obtained carries out forced air drying, until water content detection≤0.5%, obtains raw material
Medicine Lansoprazole.
Preferably, in the step A the wet crude product of Lansoprazole, alcohol solution and alkali mass ratio be 1:8~14:0.3~
2, preferably 1:11:1.65.
Preferably, the mass fraction of alcohol is 40~70% in alcohol solution in the step A, and alcohol is methanol, ethyl alcohol, positive third
Alcohol or isopropanol, preferably 55% ethanol water.
Preferably, alkali is ammonium hydroxide, ethylenediamine, triethylamine, pyridine, sodium hydroxide, potassium hydroxide, carbonic acid in the step A
Sodium, sodium bicarbonate, potassium carbonate or saleratus, preferably ammonium hydroxide, ammonium hydroxide are generally technical grade and the above rank, ammonia concn 17
~28%(w/w).
Preferably, the temperature range that stirring is warming up to dissolution in the step A is 40~70 DEG C, preferably 45~55 DEG C.
Preferably, stirring and crystallizing temperature is 0~30 DEG C, preferably 0~20 DEG C in the step B.
Preferably, the stirring and crystallizing time is 0.5~10h, preferably 0.5~2h in the step B.
Preferably, acid is glacial acetic acid, citric acid, hydrochloric acid or sulfuric acid, preferably glacial acetic acid in the step B, wherein acid is added
Amount and be added alkali amount molar ratio be 0.2~0.3:1.
Preferably, the alcohol in the step B in alcohol solution is methanol, ethyl alcohol, normal propyl alcohol or isopropanol, in aqueous alkali
Alkali be ammonium hydroxide, ethylenediamine, triethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate or carbonic acid
Hydrogen potassium at least washes twice respectively wherein the dosage of pure and mild alkali is 5~20 times of Lansoprazole quality.
Preferably, the alkali in the step C in aqueous alkali is ammonium hydroxide, ethylenediamine, triethylamine, pyridine, sodium hydroxide, hydrogen
The pH value of potassium oxide, sodium carbonate, sodium bicarbonate, potassium carbonate or saleratus, aqueous alkali controls between 7~9.
By adopting the above-described technical solution, the beneficial effects of the present invention are: the present invention is using Lansoprazole in alkalescent
Or stable under alkaline conditions is good, not oxidizable and degradation, so that impurity contains in Lansoprazole product in subtractive process
It measures low, product content can be improved, good product quality can reach the quality standard of Chinese Pharmacopoeia two middle bulk pharmaceutical chemicals Lansoprazoles；
Operation of the present invention is simple simultaneously, is easily enlarged production, with good economic efficiency, is worthy to be popularized.
Specific embodiment
Below by embodiment, technical solution of the present invention is described in further detail.
Embodiment 1
The wet crude product of 15.9g Lansoprazole, 66.4g ethyl alcohol, 51.7g purified water, 17.5g concentration are successively added into reaction flask is
28% ammonium hydroxide, stirring are warming up to 45 DEG C to dissolving, active carbon 0.23g are added, and decolourize 10min, filtering, and filtrate is down to 15 DEG C, delay
It is slow to be added dropwise 4.1 grams of glacial acetic acid, after addition, 10~15 DEG C of stirring and crystallizing 1h of temperature, filtering are controlled, filter cake successively uses 34.5g
The rinsing of 50% ethanol water and 34.5g grams of ammonia spirit (PH is about 8) rinsing twice, collect filter cake, filter cake are purified with 84g
Water agitator treating 1h, filtering, filter cake are rinsed with ammonia spirit (PH is about 8), and forced air drying obtains finished product white crystalline powder
Bulk pharmaceutical chemicals Lansoprazole 8.1g, through testing product content 99.92%, single miscellaneous 0.18%, total miscellaneous 0.27%, residue on ignition 0.08%.
Embodiment 2
It is 28% that 15.9g Lansoprazole wet product, 66.4g ethyl alcohol, 51.7g purified water, 17.5g concentration are successively added into reaction flask
Ammonium hydroxide, stirring is warming up to 50 DEG C to dissolving, active carbon 0.3g is added, and decolourize 10min, filtering, and filtrate is down to 12 DEG C hereinafter, slow
It is slow to be added dropwise 4.1 grams of glacial acetic acid, after addition, 10~15 DEG C of stirring and crystallizing 1h of temperature, filtering are controlled, filter cake successively uses 35g
The rinsing of 50% ethanol water and 35g grams of ammonia spirit (PH is about 8) rinsing twice, collect filter cake, filter cake are added to 84g PH
In about 8 ammonia spirit, 1h, filtering are stirred, filter cake is rinsed with ammonia spirit (PH is about 8), forced air drying, obtains finished product white
Crystalline powder bulk pharmaceutical chemicals Lansoprazole 8.7g, through testing product content 99.98%, single miscellaneous 0.12%, total miscellaneous 0.21% are blazing residual
Slag 0.04%.
Embodiment 3
24.3kg Lansoprazole wet product, 127.7kg ethyl alcohol, 99.8kg purified water, 33.2kg concentration are successively added into reaction kettle
For 23% ammonium hydroxide, stirring is warming up to 45 DEG C to dissolving, active carbon 0.42kg is added, and decolourize 10min, filtering, and filtrate is down to 10
DEG C, glacial acetic acid 7.7kg is slowly added dropwise, after addition, controls 10~15 DEG C of stirring and crystallizing 1h of temperature, filtering, filter cake is successively used
The rinsing of 50% ethanol water of 64kg and 64kg ammonia spirit (PH is about 8) rinsing twice, collect filter cake, by filter cake 160kg
Purified water agitator treating 1h, filtering, filter cake are rinsed with ammonia spirit (PH is about 8), and forced air drying obtains finished product white crystalline
Powder raw material medicine Lansoprazole 14.2kg, through testing product content 99.96%, single miscellaneous 0.17%, total miscellaneous 0.25%, residue on ignition
0.05%。
In above-described embodiment, forced air drying carries out stage by stage, successively are as follows: 40~45 DEG C of dry 4h, 55~60 DEG C of dry 2h,
75~80 DEG C of dry 2h.
It can be seen that operation of the present invention is simple, it is easily enlarged production；Lansoprazole is in alkalescent in entire subtractive process
Under the conditions of, Lansoprazole has good stability, not oxidizable and degradation；Gained finished product bulk pharmaceutical chemicals Lansoprazole is white after purification
Crystalline powder, condition are good；Purification gained finished product bulk pharmaceutical chemicals Lansoprazole content is greater than 99.9%, and list is miscellaneous to be not higher than 0.2%, total miscellaneous
Not higher than 0.3%, residue on ignition is not higher than 0.1%, and good product quality is much better than Chinese Pharmacopoeia two middle bulk pharmaceutical chemicals Lansoprazoles
Quality standard.
Finally it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention, rather than its limitations, although
Referring to above-described embodiment, invention is explained in detail, it should be understood by a person of ordinary skill in the art that still may be used
With modifications or equivalent substitutions are made to specific embodiments of the invention, and repaired without departing from any of spirit and scope of the invention
Change or equivalent replacement, is intended to be within the scope of the claims of the invention.
Claims (10)
1. a kind of refining methd of bulk pharmaceutical chemicals Lansoprazole, which comprises the steps of:
Step A: the wet crude product of Lansoprazole, alcohol solution and alkali are added in reaction kettle by a certain percentage, and stirring is warming up to molten
Active carbon is added in solution, and decolourize 10~30min, filters pressing to crystallizing tank；
Step B: the filtrate that step A is obtained in crystallizing tank is cooled to 20 DEG C hereinafter, being slowly added to acid, stirring and crystallizing filters, filter
Cake is washed with alcohol solution and aqueous alkali respectively, collects filter cake；
Step C: the obtained filter cake of step B being added in purified water or aqueous alkali, agitator treating, filtering, filter cake buck
Solution washing, obtains the wet fine work of Lansoprazole；
Step D: the wet fine work of the Lansoprazole that step C is obtained carries out forced air drying, until water content detection≤0.5%, obtains raw material
Medicine Lansoprazole.
2. the refining methd of bulk pharmaceutical chemicals Lansoprazole according to claim 1, it is characterised in that: blue rope in the step A
The mass ratio for drawing the wet crude product of azoles, alcohol solution and alkali is 1:8~14:0.3~2.
3. the refining methd of bulk pharmaceutical chemicals Lansoprazole according to claim 1, it is characterised in that: alcohol water in the step A
The mass fraction of alcohol is 40~70% in solution, and alcohol is methanol, ethyl alcohol, normal propyl alcohol or isopropanol.
4. the refining methd of bulk pharmaceutical chemicals Lansoprazole according to claim 1, it is characterised in that: alkali is in the step A
Ammonium hydroxide, ethylenediamine, triethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate or saleratus.
5. the refining methd of bulk pharmaceutical chemicals Lansoprazole according to claim 1, it is characterised in that: stirred in the step A
The temperature range for being warming up to dissolution is 40~70 DEG C.
6. the refining methd of bulk pharmaceutical chemicals Lansoprazole according to claim 1, it is characterised in that: stirred in the step B
Crystallization temperature is 0~30 DEG C.
7. the refining methd of bulk pharmaceutical chemicals Lansoprazole according to claim 1, it is characterised in that: stirred in the step B
The crystallization time is 0.5~10h.
8. the refining methd of bulk pharmaceutical chemicals Lansoprazole according to claim 1, it is characterised in that: acid is in the step B
Glacial acetic acid, citric acid, hydrochloric acid or sulfuric acid, wherein the molar ratio that the amount of acid is added and the amount of alkali is added is 0.2~0.3:1.
9. the refining methd of bulk pharmaceutical chemicals Lansoprazole according to claim 1, it is characterised in that: alcohol water in the step B
Alcohol in solution is methanol, ethyl alcohol, normal propyl alcohol or isopropanol, the alkali in aqueous alkali be ammonium hydroxide, ethylenediamine, triethylamine, pyridine,
Sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate or saleratus, wherein the dosage of pure and mild alkali is Lansoprazole
5~20 times of quality, at least wash twice respectively.
10. the refining methd of bulk pharmaceutical chemicals Lansoprazole according to claim 1, it is characterised in that: buck in the step C
Alkali in solution is ammonium hydroxide, ethylenediamine, triethylamine, pyridine, sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, potassium carbonate
Or saleratus, the pH value of aqueous alkali control between 7~9.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811189736.2A CN109265442A (en) | 2018-10-12 | 2018-10-12 | A kind of refining methd of bulk pharmaceutical chemicals Lansoprazole |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811189736.2A CN109265442A (en) | 2018-10-12 | 2018-10-12 | A kind of refining methd of bulk pharmaceutical chemicals Lansoprazole |
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| Publication Number | Publication Date |
|---|---|
| CN109265442A true CN109265442A (en) | 2019-01-25 |
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| CN201811189736.2A Pending CN109265442A (en) | 2018-10-12 | 2018-10-12 | A kind of refining methd of bulk pharmaceutical chemicals Lansoprazole |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113956200A (en) * | 2021-12-16 | 2022-01-21 | 南京威凯尔生物医药科技有限公司 | Crystallization process of roxasistat bulk drug with controlled particle size |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004018454A1 (en) * | 2002-08-21 | 2004-03-04 | Teva Pharmaceutical Industries Ltd. | A method for the purification of lansoprazole |
| WO2004046135A1 (en) * | 2002-11-18 | 2004-06-03 | Teva Pharmaceutical Industries Ltd. | Stable lansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol |
| CN101289443A (en) * | 2008-06-10 | 2008-10-22 | 上海慈瑞医药科技有限公司 | Method for refining lansoprazole bulk drug |
| CN105037327A (en) * | 2015-03-06 | 2015-11-11 | 海南海力制药有限公司 | Purifying method of dextral lansoprazole anhydrous substance |
| CN106478600A (en) * | 2016-09-27 | 2017-03-08 | 苏州天马精细化学品股份有限公司 | A kind of process for purification of Lansoprazole |
| CN106928191A (en) * | 2015-12-30 | 2017-07-07 | 河南康达制药有限公司 | A kind of preparation technology of Lansoprazole |
-
2018
- 2018-10-12 CN CN201811189736.2A patent/CN109265442A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004018454A1 (en) * | 2002-08-21 | 2004-03-04 | Teva Pharmaceutical Industries Ltd. | A method for the purification of lansoprazole |
| WO2004046135A1 (en) * | 2002-11-18 | 2004-06-03 | Teva Pharmaceutical Industries Ltd. | Stable lansoprazole containing more than 500 ppm, up to about 3,000 ppm water and more than 200 ppm, up to about 5,000 ppm alcohol |
| CN101289443A (en) * | 2008-06-10 | 2008-10-22 | 上海慈瑞医药科技有限公司 | Method for refining lansoprazole bulk drug |
| CN105037327A (en) * | 2015-03-06 | 2015-11-11 | 海南海力制药有限公司 | Purifying method of dextral lansoprazole anhydrous substance |
| CN106928191A (en) * | 2015-12-30 | 2017-07-07 | 河南康达制药有限公司 | A kind of preparation technology of Lansoprazole |
| CN106478600A (en) * | 2016-09-27 | 2017-03-08 | 苏州天马精细化学品股份有限公司 | A kind of process for purification of Lansoprazole |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113956200A (en) * | 2021-12-16 | 2022-01-21 | 南京威凯尔生物医药科技有限公司 | Crystallization process of roxasistat bulk drug with controlled particle size |
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Application publication date: 20190125 |