CN1042423C - Omeprazole salt hydrate and preparation method thereof - Google Patents
Omeprazole salt hydrate and preparation method thereof Download PDFInfo
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- CN1042423C CN1042423C CN95111640A CN95111640A CN1042423C CN 1042423 C CN1042423 C CN 1042423C CN 95111640 A CN95111640 A CN 95111640A CN 95111640 A CN95111640 A CN 95111640A CN 1042423 C CN1042423 C CN 1042423C
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- Prior art keywords
- omeprazole
- salt hydrate
- hydrate
- preparation
- aomeilazole
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- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical class N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 239000003112 inhibitor Substances 0.000 claims abstract description 18
- 210000004211 gastric acid Anatomy 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 57
- 229960000381 omeprazole Drugs 0.000 claims description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 238000005342 ion exchange Methods 0.000 claims description 14
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 8
- 239000011347 resin Substances 0.000 claims description 6
- 229920005989 resin Polymers 0.000 claims description 6
- 230000001476 alcoholic effect Effects 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- 239000013557 residual solvent Substances 0.000 abstract description 4
- 208000007107 Stomach Ulcer Diseases 0.000 abstract description 2
- 208000000718 duodenal ulcer Diseases 0.000 abstract description 2
- 201000005917 gastric ulcer Diseases 0.000 abstract description 2
- 238000010253 intravenous injection Methods 0.000 abstract description 2
- 231100000086 high toxicity Toxicity 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000000843 powder Substances 0.000 abstract 1
- 231100000331 toxic Toxicity 0.000 abstract 1
- 230000002588 toxic effect Effects 0.000 abstract 1
- RRFCKCAQHRITRG-UHFFFAOYSA-N sodium;5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]benzimidazol-3-ide;hydrate Chemical compound O.[Na+].N=1C2=CC(OC)=CC=C2[N-]C=1S(=O)CC1=NC=C(C)C(OC)=C1C RRFCKCAQHRITRG-UHFFFAOYSA-N 0.000 description 39
- 229960004756 ethanol Drugs 0.000 description 20
- 239000000243 solution Substances 0.000 description 18
- 229940063517 omeprazole sodium Drugs 0.000 description 15
- 230000008676 import Effects 0.000 description 8
- 239000008176 lyophilized powder Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 229960000935 dehydrated alcohol Drugs 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 235000011121 sodium hydroxide Nutrition 0.000 description 6
- 239000012535 impurity Substances 0.000 description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000011521 glass Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000007599 discharging Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 235000011118 potassium hydroxide Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000000967 suction filtration Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229940083608 sodium hydroxide Drugs 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000002211 ultraviolet spectrum Methods 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- GCFHZZWXZLABBL-UHFFFAOYSA-N ethanol;hexane Chemical compound CCO.CCCCCC GCFHZZWXZLABBL-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000001869 rapid Effects 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- -1 sodium alkoxide Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The present invention relates to an omeprazole salt hydrate and a preparation method thereof. Omeprazole salt is an excellent gastric acid inhibitor, but clinical application is affected due to poor stability and high toxicity of residual solvents. The omeprazole salt hydrate provided by the invention has good stability and high purity, does not contain toxic residual solvent, and can be used for preparing freeze-dried powder for intravenous injection and oral preparations for treating gastric ulcer and duodenal ulcer. The preparation method of the invention has simple process and is suitable for industrial production.
Description
The invention belongs to Aomeilazole salt hydrate for gastric acid inhibitor and preparation method thereof.
Form of omeprazole salts (5-methoxyl group-2-[[(4-methoxyl group-3,5-dimethyl-2-pyridyl) methyl] sulfinyl]-1H-benzoglyoxaline salt hydrate) be a kind of good acid inhibitor.Existing many pieces of patent reports form of omeprazole salts and its production and application, as GB2137616, ES2023778 and ES2024993 etc.But, because the water absorbability of form of omeprazole salts descends significantly at the suction rear stability.Influence its clinical application.In addition, there are some defectives in prior preparation method.For example the method for preparing Omeprazole Sodium of report is to adopt omeprazole and sodium hydroxide, sodium alkoxide or the reaction of acetylacetic ester sodium at present, sees reaction formula one
Wherein R=OH-, CH
3O-, CH
3C-CH
2CO-, CH
3Adopted water, ethyl acetate, tetrahydrofuran (THF), trieline equal solvent in this method of C-CHCOR ', the Omeprazole Sodium purity of preparation is not high, also accompanies solvent sometimes, can produce certain toxicity.
The object of the invention is in order to solve toxicity problem form of omeprazole salts, stability and residual solvent, through the hydrate of trial production success form of omeprazole salts.This hydrate is difficult for absorbing, good stability, and can adopt the omeprazole crude product to prepare highly purified Aomeilazole salt hydrate for gastric acid inhibitor.
The invention provides the Aomeilazole salt hydrate for gastric acid inhibitor of formula I.(5-methoxyl group-2-[[(4-methoxyl group-3,5-dimethyl-2-pyridyl) methyl] sulfinyl]-1H-benzoglyoxaline salt hydrate)
Wherein M is Na, K.
Aomeilazole salt hydrate for gastric acid inhibitor of the present invention [I] is proved conclusively by following method:
1, TGA (thermal weight loss) and DSC (differential scanning) analyze, and have confirmed to contain crystal water in its structure.By test result as seen, thermal weight loss is 4.75%.Conform to calculated value 4.68%, the dehydration starting temperature is 124.8 ℃.(seeing Fig. 1, Fig. 2)
Fig. 1 Aomeilazole salt hydrate for gastric acid inhibitor hot weightless picture
Fig. 2 Omeprazole Sodium-hydrate differential scanning calorimetry figure
2, scanning electron microscopy analysis (see figure 3)
Fig. 3 Aomeilazole salt hydrate for gastric acid inhibitor sem photograph
3, as follows through C, H, N results of elemental analyses:
Elements C H N O S
Theoretical value 52.97% 5.23% 10.90% 16.60% 8.32%
Measured value 52.95% 5.23% 10.85% 16.78% 8.37%
4, measure the content of water in the Aomeilazole salt hydrate for gastric acid inhibitor with the Ka Shi method, the result is 4.55.0%.
5, the rotating anode X-ray diffraction is analyzed, and compares with Omeprazole Sodium, and its crystalline structure is different fully.(seeing Fig. 4, Fig. 5)
Fig. 4 Omeprazole Sodium-hydrate rotating anode X-ray diffractogram
Fig. 5 Omeprazole Sodium rotating anode X-ray diffractogram
Said structure has confirmed that Omeprazole Sodium of the present invention has crystal water.
6, infrared spectra (IR) is analyzed: (seeing Fig. 6, Fig. 7)
Fig. 6 Omeprazole Sodium-hydrate infrared spectrogram
Fig. 7 import Astra company's omeprazole lyophilized powder (containing little water) infrared spectrogram
7, UV spectrum (UV) is analyzed: (see Fig. 8-Figure 11)
Fig. 8 Omeprazole Sodium-hydrate ultraviolet spectrogram (95% alcohol solvent)
Fig. 9 Omeprazole Sodium-hydrate ultraviolet spectrogram (0.1mol1
-1The NaOH aqueous solution is made solvent)
Figure 10 import Astra company's omeprazole lyophilized powder (containing little water) ultraviolet spectrogram (95% alcohol solvent)
Figure 11 import Astra company's omeprazole lyophilized powder (containing little water) ultraviolet spectrogram (0.1mol.1
-1The NaOH aqueous solution is made solvent)
8, nucleus magnetic resonance (H-NME) analysis (
13C-NMR) analyze: (see Figure 12-Figure 19)
Figure 12 Omeprazole Sodium-hydrate ' H-NMR schemes (D
2O makes solvent) testing tool Bruker, Am-300
Figure 13 import Astra company's omeprazole lyophilized powder (containing little water) ' H-NMR figure
Figure 14 Omeprazole Sodium-hydrate
12C-NMR schemes (D
2O makes solvent)
Figure 15 Omeprazole Sodium-hydrate Dept90 ℃ figure
Figure 16 Omeprazole Sodium-hydrate Dept135 ℃ figure
Figure 17 import Astra company's omeprazole lyophilized powder (containing little water)
13C-NMR figure
Dept90 ℃ of figure of Figure 18 import Astra company's omeprazole lyophilized powder (containing little water)
Dept135 ℃ of figure of Figure 19 import Astra company's omeprazole lyophilized powder (containing little water)
9, the mass spectrum MS omeprazole lyophilisate contrast (seeing Figure 20, Figure 21) analyzing and produce with Sweden Astra company
Figure 20 Omeprazole Sodium-hydrate MS schemes (FAB, mono-nitration glycerine is made substrate)
Figure 21 import Astra company's omeprazole lyophilized powder (containing little water) MS schemes (FAB, mono-nitration glycerine is made substrate)
The above results shows: omeprazole anion structure and Omeprazole Sodium in the omeprazole sodium hydrate (I) are in full accord.
The result is as follows: 1, humid test through humidity, temperature, light durability investigation for omeprazole sodium hydrate of the present invention:
Condition: 40 ℃ of dew of 80% relative humidity were put ten days.
Content result:
Annotate: measure content with HPLC, measure moisture content with the Ka Shi method, content calculates with dry product.2, humid test:
| % before placing | % after ten days | Content decline % | |
| Omeprazole Sodium | 98.2 | 96.0 | 2.2 |
| Omeprazole sodium hydrate (I) | 99.6 | 99.4 | 0.2 |
Condition: 60 ℃ of glass are airtight, two weeks.
Content result:
| % before placing | Two week back % | Content decline % | |
| Omeprazole Sodium | 98.2 | 97.8 | 0.4 |
| Omeprazole sodium hydrate (I) | 99.6 | 99.3 | 0.3 |
Annotate: content assaying method: HPLC
3, exposure experiments to light:
Condition: 2000nX, a week
Content result:
| % before placing | One week of illumination back % | Content decline % | |
| Omeprazole Sodium | 98.2 | 94.6 | 3.4 |
| Omeprazole sodium hydrate (I) | 99.6 | 97.1 | 2.5 |
Annotate: content assaying method: HPLC
4, product purity contrast:
Annotate: content assaying method: HPLC, impurity determination method: TLC
| Content % | The impurity spot | |
| Omeprazole Sodium | ＜98.5 | Have |
| Omeprazole sodium hydrate (I) | ＞99.5 | Do not have |
Prove by above-mentioned test-results; Omeprazole sodium hydrate (I) obviously is better than Omeprazole Sodium to the stability of humidity; Stability to temperature and illumination also is better than Omeprazole Sodium; Product purity is apparently higher than Omeprazole Sodium.
Another object of the present invention has provided the preparation method of omeprazole sodium hydrate (I).(seeing reaction formula two)
OM is an omeprazole
The preparation method of omeprazole sodium hydrate of the present invention comprises the following steps: that (1) use NaCl solution, NaOH solution and water treatment D201 resin in order respectively; (2) resin that will handle is packed in the ion exchange column, and is full of full post with ethanol; (3) after omeprazole is dissolved in alcohol, the omeprazole ethanolic soln is entered above-mentioned ion exchange column from the upper end of ion exchange column adsorb; (4) MOH is dissolved in aqueous alcohol, and this solution is pressed into step from the lower end of ion exchange column
(3) in the ion exchange column;
(5) collect the omeprazole salts solution, be evaporated to 1/4 volume from the upper end of step (4) ion exchange column, add 2 times of amount organic solvents and separate out solid, filtration, drying make Aomeilazole salt hydrate for gastric acid inhibitor.
Alcohol used in above-mentioned preparation method's step (2) can be C
1-C
3Alcohols; MOH in the step (4) can be NaOH or KOH; Organic solvent in the step (5) can be sherwood oil or C
5-C
8Alkane.
The ion-exchange column device that uses among the preparation method of the present invention is seen Figure 22
Figure 22 ion-exchange column device
Wherein 1. contain omeprazole alcoholic solution container
2. porous pressing plate
3.D201 anionite-exchange resin
4. porous supporting plate
5. contain the alkaline solution container
Aomeilazole salt hydrate for gastric acid inhibitor of the present invention and form of omeprazole salts have same therapeutic action, can be used for preparing lyophilisate and the oral preparations treatment stomach ulcer and the duodenal ulcer of used for intravenous injection.Such stability of formulation is good.Form of omeprazole salts preparation method technology provided by the invention is simple, product purity is high, do not contain the toxicity residual solvent, and can directly prepare Aomeilazole salt hydrate for gastric acid inhibitor with rough omeprazole product, is suitable for suitability for industrialized production.
Example one, preparation omeprazole sodium hydrate
In the glass tube column of a 1.4cm * 150cm (lower end connects a piston, and the upper end connects a mouth), be full of the D201 resin of crossing through sodium-hydroxide treatment (160 gram).(device is seen Figure 22) adds in the post from the upper end with dehydrated alcohol earlier, after treating to be full of ethanol in the post, opens the lower end piston, and the control discharging amount keeps ethanol to be full of full post, when upper end ethanol adds, closes the lower end piston immediately.34.5g (0.1mol) omeprazole is dissolved in the 700ml ethanol, adds, open the lower end piston simultaneously, regulate discharge, make above-mentioned solution in 56 hours, pass through post, continue to add an amount of dehydrated alcohol and wash post, to remove impurity from the post upper end.Keep ethanol to be full of full post, close the lower end piston.In (1) container, add 3.2gNaOH and 800ml95% alcoholic acid solution.Be pressed in the post from the lower end, and open the lower end piston, the joint press-in speed that withers, control post upper end discharge finishes the back and continues to pass through post with 200ml95% ethanol at 100ml per hour.Collect high purity omeprazole sodium ethoxide solution 900ml from the upper end, (removing beginning effluent liquid 200ml) is concentrated into resid vol 200ml with this solution pressure, add the 400ml normal hexane, stir, after solid is separated out, be cooled to 5 ℃, stirred 6 hours, suction filtration, solid washs 40 ℃ of drying under reduced pressure with ethanol normal hexane mixed solvent, get omeprazole sodium hydrate 30g, purity 99.5%.(the HPLC method is measured content, and dry product calculates to anhydrate).
Example two, preparation omeprazole sodium hydrate
In the glass tube column of a 4.7cm * 200cm, device adds in the post, after treating to be full of ethanol in the post from upper end (2) with dehydrated alcohol earlier as example 1, open the lower end piston, the control discharging amount keeps ethanol to be full of full post, when upper end ethanol adds, close the lower end piston immediately.1.035kg (3mol) omeprazole is dissolved in the 20L dehydrated alcohol, adds from post upper end (2), open the lower end piston simultaneously, the throttling output of withering made above-mentioned solution pass through post in 5-6 hour.Continue to add dehydrated alcohol and wash post,, keep ethanol to be full of full post, turn off the lower end piston to remove impurity.Add 72gNaOH and 9L95% alcoholic acid solution in (1) container, be pressed in the post from the lower end, and open the lower end piston, regulate press-in speed, control post upper end discharge continues pass through post with 5L95% at 2L per hour after finishing.Collect high purity omeprazole sodium ethoxide solution from last rapids, (removing beginning effluent liquid 3.2L) is concentrated into volume 5L with this solution decompression, add the 10L normal hexane, stir, after solid is separated out, be cooled to 5 ℃, stirred 5 hours, suction filtration, solid washs with ethanol normal hexane mixing solutions, 40 ℃ of drying under reduced pressure get omeprazole sodium hydrate 0.65kg.
Continuation drops into the 0.62kg omeprazole in exchange column (2) container and the 12L ethanol solution repeats as above to operate, but the product of continuous production high purity omeprazole sodium hydrate.
Example three, preparation omeprazole potassium hydrate
In the glass tube column of a 1.4cm * 150cm, (device is seen Figure 22).Add in the post from the upper end with dehydrated alcohol earlier, after treating to be full of ethanol in the post, open the lower end piston, the control discharging amount keeps ethanol to be full of full post.When upper end ethanol adds, close the lower end piston immediately.34.5 gram (0.1mol) omeprazoles are dissolved in the 700ml ethanol, add, open the lower end piston simultaneously, regulate discharge, make above-mentioned solution in 5-6 hour, pass through post from the post upper end.Continue to add an amount of dehydrated alcohol and wash post, to remove impurity.Keep ethanol to be full of full post, close the lower end piston.Add KOH4.48g and 800ml95% alcoholic acid solution in (1) container, be pressed in the post from the lower end, and open the lower end piston, regulate press-in speed, discharge after the end, continues pass through post with 200ml95% ethanol at 100ml per hour on the control post.Collect high purity omeprazole potassium ethanolic soln 900ml from the upper end, (removing beginning effluent liquid 200ml) is concentrated into volume 200ml with this solution decompression, add the 400ml normal hexane, stir, after solid is separated out, be cooled to 5 ℃, stirred 6 hours, suction filtration, solid washs with ethanol hexane mixed solvent, 40 ℃ of drying under reduced pressure, get omeprazole potassium hydrate 31g, purity 99.5% (the HPLC method is measured content, and dry product calculates to anhydrate).
Claims (4)
1, a kind of Aomeilazole salt hydrate for gastric acid inhibitor with formula I is characterized in that this hydrate contains crystal water,
Wherein M is Na, K.
2, a kind of preparation method of Aomeilazole salt hydrate for gastric acid inhibitor as claimed in claim 1 is characterized in that this method comprises the following steps: that (1) use NaCl solution, NaOH solution and water treatment D201 resin in order respectively; (2) resin that will handle is packed in the ion exchange column, and is full of full post with alcohol; (3) after omeprazole is dissolved in alcohol, the omeprazole alcoholic solution is entered above-mentioned ion exchange column from the upper end of ion exchange column adsorb; (4) NaOH or KOH are dissolved in aqueous alcohol, the lower end of this solution from ion exchange column is pressed in the ion exchange column of step (3); (5) collect the omeprazole salts solution, be evaporated to 1/4 volume from the upper end of step (4) ion exchange column, add 2 times of amount organic solvents and separate out solid, filtration, drying make Aomeilazole salt hydrate for gastric acid inhibitor.
3, the preparation method of Aomeilazole salt hydrate for gastric acid inhibitor according to claim 2 is characterized in that wherein the used alcohol of step (2) is C
1-C
3Alkyl alcohol.
4, the preparation method of Aomeilazole salt hydrate for gastric acid inhibitor according to claim 2 is characterized in that the wherein organic solvent of step (5), is sherwood oil or C
5-C
8Alkane.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95111640A CN1042423C (en) | 1995-05-25 | 1995-05-25 | Omeprazole salt hydrate and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95111640A CN1042423C (en) | 1995-05-25 | 1995-05-25 | Omeprazole salt hydrate and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1136564A CN1136564A (en) | 1996-11-27 |
| CN1042423C true CN1042423C (en) | 1999-03-10 |
Family
ID=5078906
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN95111640A Expired - Lifetime CN1042423C (en) | 1995-05-25 | 1995-05-25 | Omeprazole salt hydrate and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1042423C (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE510650C2 (en) | 1997-05-30 | 1999-06-14 | Astra Ab | New association |
| US6747155B2 (en) | 1997-05-30 | 2004-06-08 | Astrazeneca Ab | Process |
| SE510643C2 (en) * | 1997-06-27 | 1999-06-14 | Astra Ab | Thermodynamically stable omeprazole sodium form B |
| EP1907375B1 (en) * | 2005-06-08 | 2013-07-24 | LEK Pharmaceuticals d.d. | Crystalline solvate of omeprazole sodium |
| CN101412710B (en) * | 2008-12-16 | 2010-04-21 | 海南百那医药发展有限公司 | Omeprazole sodium compound and preparation thereof |
| CN102319223B (en) * | 2011-09-21 | 2013-06-19 | 石药集团欧意药业有限公司 | Esomeprazole freeze-dried preparation and preparation method thereof |
| CN102512380B (en) * | 2011-12-20 | 2013-04-17 | 海南锦瑞制药股份有限公司 | Freeze-dried powder injection with omeprazole sodium as active component and preparation method thereof |
| CN104788426B (en) * | 2015-04-02 | 2015-12-30 | 天津大学 | A kind of Omeprazole Sodium semihydrate and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2137616A (en) * | 1983-03-04 | 1984-10-10 | Haessle Ab | Novel compounds |
-
1995
- 1995-05-25 CN CN95111640A patent/CN1042423C/en not_active Expired - Lifetime
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2137616A (en) * | 1983-03-04 | 1984-10-10 | Haessle Ab | Novel compounds |
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| Publication number | Publication date |
|---|---|
| CN1136564A (en) | 1996-11-27 |
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