CN103709140A - Pantoprazole sodium crystal and preparation method thereof - Google Patents
Pantoprazole sodium crystal and preparation method thereof Download PDFInfo
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- CN103709140A CN103709140A CN201310472625.3A CN201310472625A CN103709140A CN 103709140 A CN103709140 A CN 103709140A CN 201310472625 A CN201310472625 A CN 201310472625A CN 103709140 A CN103709140 A CN 103709140A
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- 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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Abstract
The invention relates to three new pantoprazole sodium crystal forms comprising a crystal form W, a crystal form Y and a crystal form Z. The discovery of the new crystal forms of an active pharmaceutical ingredient provides more possibilities for improvement of final drug product features, as well as provides a broader space for medicine researchers to design prescriptions.
Description
Technical field
The invention belongs to field of medicaments, particularly crystal of Pantoprazole Sodium and preparation method thereof.
Background technology
Pantoprazole Sodium, chemistry 5-difluoro-methoxy-2-[(3 by name, 4-dimethoxy-2-pyridinyl) methyl] sulfinyl-1H-benzoglyoxaline sodium salt, its structural formula is as follows.Be a kind of proton pump inhibitor, can be used for treatment and the disorderly relevant disease of gastric acid secretion.
Kohl, the people such as B, at document J. Med. Chem. 1992,35, have reported times semihydrate of Pantoprazole Sodium in 1049-1057.
International monopoly WO 91/19710 discloses the monohydrate of Pantoprazole Sodium.
International monopoly WO 2004056804 discloses a series of polymorphics and the solvate of Pantoprazole Sodium, comprising:
Acetone solvate form IV, n-butanol solvent compound crystal form V, butanone solvent compound crystal form V III, dimethyl carbonate solvent compound crystal formation IX, n-propyl alcohol solvate crystal form X, anhydrous pantoprazole crystal form X I, iso-butanol solvent compound crystal form X II, water-butanone solvent compound crystal form X VII, boiling solvate crystal form X VIII, dihydrate crystal form X IX, trihydrate crystal form X X, amorphous state Pantoprazole Sodium and hydrate crystal forms II, VI, XIII, XIV, XV, XVI.
International monopoly WO 2004099183 discloses pantoprazole sodium crystal I, crystal form II and amorphous substance.
International monopoly WO 2004100949 discloses a series of polymorphics and the solvate of Pantoprazole Sodium, comprising:
Hydrate crystal forms N, acetone-water compound crystal form A 1, A2, A3, A4, methyl acetate-hydrate crystal forms B1, B2, B3, butanone-hydrate crystal forms C1, C2, the hydrate crystal forms E1 of metacetone-hydrate crystal forms D1 and desolventizing.
US Patent No. 20040186139 discloses the preparation of Pantoprazole Sodium sesquialter hydrate crystal forms I.
US Patent No. 20050245578 discloses the acetone-monohydrate crystal form of Pantoprazole Sodium, butanone-monohydrate crystal form, metacetone-monohydrate crystal form, and methyl iso-butyl ketone (MIBK)-monohydrate crystal form.
International monopoly WO 2007091276 discloses Pantoprazole Sodium crystal form II I and form IV.
Chinese patent CN102796078 also discloses a kind of new crystal of pantoprazole sodium-hydrate.
Summary of the invention
The invention provides three kinds of new crystal that Pantoprazole Sodium is unlike the prior art provided, at this difference called after crystal formation W, crystal formation Y and crystal formation Z.
In one embodiment, the invention provides pantoprazole sodium crystal W.Its PXRD(Powder X-Ray Diffraction powder x-ray diffraction) in collection of illustrative plates, source of radiation is CuK α 1, in angle of diffraction 2 θ values, be 5.33, 6.30, 7.66, 12.59, 13.99, 14.80, 17.21, 18.38, 19.72, 21.38, there is stronger diffraction peak at 24.18 places, in angle of diffraction 2 θ values, be 5.76, 8.72, 8.98, 9.34, 10.38, 10.64, 11.05, 11.49, 13.03, 13.76, 16.46, 17.78, 18.71, 20.09, 20.82, 22.13, 22.51, 23.07, 23.33, 23.67, 24.87, 25.33, 26.45, 27.64, 28.72, 29.20, 30.97, 31.4, 33.81, 34.82, 36.48, there is weak diffraction peak at 37.11 places, wherein 2 θ value limit of error are ± 0.2, its DSC(Differential Scanning Calorimetry means of differential scanning calorimetry) collection of illustrative plates has endotherm(ic)peak at 167 ± 5 ℃.
The invention provides the preparation method of a kind of pantoprazole sodium crystal W: under room temperature, by Pantoprazole Sodium times semihydrate stirring suspension in Isosorbide-5-Nitrae-dioxane, filter.
In one embodiment, the invention provides pantoprazole sodium crystal Y.In its PXRD collection of illustrative plates, source of radiation is CuK α 1, in angle of diffraction 2 θ values, be that 6.71,15.77,20.13,20.85,23.25,23.53,27.65,29.25 places have stronger diffraction peak, in angle of diffraction 2 θ values, be that 13.28,13.76,17.15,18.99,21.57,24.75,25.72,26.39,26.65,32.17,32.65,33.84,36.18,37.27,41.04,43.68 places have weak diffraction peak, wherein 2 θ value limit of error are ± 0.2; Its DSC collection of illustrative plates has endotherm(ic)peak at 140 ± 5 ℃.
The invention provides the preparation method of a kind of pantoprazole sodium crystal Y: under room temperature, a Pantoprazole Sodium times semihydrate is dissolved in tetrahydrofuran (THF), after filtering that filtrate is standing, slowly volatilization, after solvent all volatilizes, solid is taken out, with the drip washing of Isosorbide-5-Nitrae-dioxane.
In another embodiment, the invention provides pantoprazole sodium crystal Z.In its PXRD collection of illustrative plates, source of radiation is CuK α 1, in angle of diffraction 2 θ values, be 5.43, 11.84, 12.93, 13.58, 15.26, 16.21, 16.42, 18.20, 21.65, 25.01, 25.82, there is stronger diffraction peak at 26.27 places, in angle of diffraction 2 θ values, be 10.36, 14.27, 17.35, 19.13, 19.54, 20.41, 21.32, 21.95, 22.90, 23.12, 23.79, 24.55, 25.42, 27.38, 27.71, 28.13, 28.37, 29.65, 29.92, 32.02, 32.98, 33.36, 33.79, 34.52, 35.00, 35.97, 37.07, 39.70, there is weak diffraction peak at 40.48 places, wherein 2 θ value limit of error are ± 0.2, its DSC collection of illustrative plates has two endotherm(ic)peaks at 76 ± 5 ℃, 157 ± 5 ℃.
The invention provides the preparation method of a kind of pantoprazole sodium crystal Z: under room temperature, a Pantoprazole Sodium times semihydrate is dissolved in 2-butanone, after filtering that filtrate is standing, slowly evaporate into crystallize out, filter.
PXRD testing method of the present invention: instrument model: Bruker D8 advance XRD, diffracted ray: CuK α 1 (40 kV, 40 mA), scanning speed: 8 °/min (2 θ value), sweep limit: 3 ° ~ 45 ° (2 θ value); DSC testing method: instrument model: TA Q2000,10 ℃/min of temperature rise rate.
Accompanying drawing explanation
Fig. 1 is the XRPD collection of illustrative plates of pantoprazole sodium crystal W of the present invention.
Fig. 2 is the DSC collection of illustrative plates of pantoprazole sodium crystal W of the present invention.
Fig. 3 is the XRPD collection of illustrative plates of pantoprazole sodium crystal Y of the present invention.
Fig. 4 is the DSC collection of illustrative plates of pantoprazole sodium crystal Y of the present invention.
Fig. 5 is the XRPD collection of illustrative plates of pantoprazole sodium crystal Z of the present invention.
Fig. 6 is the DSC collection of illustrative plates of pantoprazole sodium crystal Z of the present invention.
embodiment
embodiment 1the preparation of pantoprazole sodium crystal W
Take 1 g Pantoprazole Sodium times semihydrate in container, add 5 ml Isosorbide-5-Nitrae-dioxane, after stirring at room suspends 4 days, after filtration, vacuum-drying, obtain white powder.
Fig. 1 is shown in by its PXRD collection of illustrative plates, and source of radiation is CuK α
1, in angle of diffraction 2 θ values, be 5.33, 6.30, 7.66, 12.59, 13.99, 14.80, 17.21, 18.38, 19.72, 21.38, there is stronger diffraction peak at 24.18 places, in angle of diffraction 2 θ values, be 5.76, 8.72, 8.98, 9.34, 10.38, 10.64, 11.05, 11.49, 13.03, 13.76, 16.46, 17.78, 18.71, 20.09, 20.82, 22.13, 22.51, 23.07, 23.33, 23.67, 24.87, 25.33, 26.45, 27.64, 28.72, 29.20, 30.97, 31.4, 33.81, 34.82, 36.48, there is weak diffraction peak at 37.11 places, wherein 2 θ value limit of error are ± 0.2.
Fig. 2 is shown in by its DSC collection of illustrative plates, at 167 ± 5 ℃, has endotherm(ic)peak.
embodiment 2the preparation of pantoprazole sodium crystal Y
Take 1 g Pantoprazole Sodium times semihydrate in container, add 40 ml tetrahydrofuran (THF)s, stirring at room to solid dissolves completely, elimination insolubles, filtrate is placed in open container, slowly volatilization in Fume Hoods, after solvent all volatilizes, solid is taken out, with the drip washing of Isosorbide-5-Nitrae-dioxane (3 * 15 ml), after vacuum-drying, obtain white crystal.
Fig. 3 is shown in by its PXRD collection of illustrative plates, and source of radiation is CuK α
1in angle of diffraction 2 θ values, be that 6.71,15.77,20.13,20.85,23.25,23.53,27.65,29.25 places have stronger diffraction peak, in angle of diffraction 2 θ values, be that 13.28,13.76,17.15,18.99,21.57,24.75,25.72,26.39,26.65,32.17,32.65,33.84,36.18,37.27,41.04,43.68 places have weak diffraction peak, wherein 2 θ value limit of error are ± 0.2.
Fig. 4 is shown in by its DSC collection of illustrative plates, at 140 ± 5 ℃, has endotherm(ic)peak.
embodiment 3the preparation of pantoprazole sodium crystal Z
Take 1 g Pantoprazole Sodium times semihydrate in container, add 40 ml 2-butanone, stirring at room to solid dissolves completely, elimination insolubles, filtrate is placed in open container, slowly volatilization in Fume Hoods, after 2 days, in container, separate out solid, after filtration, vacuum-drying, obtain white crystal.
Fig. 5 is shown in by its PXRD collection of illustrative plates, and source of radiation is CuK α
1, in angle of diffraction 2 θ values, be 5.43, 11.84, 12.93, 13.58, 15.26, 16.21, 16.42, 18.20, 21.65, 25.01, 25.82, there is stronger diffraction peak at 26.27 places, in angle of diffraction 2 θ values, be 10.36, 14.27, 17.35, 19.13, 19.54, 20.41, 21.32, 21.95, 22.90, 23.12, 23.79, 24.55, 25.42, 27.38, 27.71, 28.13, 28.37, 29.65, 29.92, 32.02, 32.98, 33.36, 33.79, 34.52, 35.00, 35.97, 37.07, 39.70, there is weak diffraction peak at 40.48 places, wherein 2 θ value limit of error are ± 0.2.
Fig. 6 is shown in by its DSC collection of illustrative plates, at 76 ± 5 ℃, 157 ± 5 ℃, has two endotherm(ic)peaks.
Same medicine, crystal formation is different, and the solid state physical properties such as its mobility, compressibility, solvability are also not quite similar, and these character produce certain impact to the prescription of medicine, administering mode etc.The final medicament production characteristic of improvement that is found to be of active pharmaceutical ingredient new crystal provides more possibilities, also for medical research staff designs prescription, provides more wide space simultaneously.
Be only above with general explanation, embodiment and test, the present invention has been made to detailed description, and unrestricted the present invention.On basis of the present invention, can make some modifications or improvements it, these modifications or improvements, all belong to the scope of protection of present invention without departing from theon the basis of the spirit of the present invention.
Claims (15)
1. a pantoprazole sodium crystal W, in its PXRD collection of illustrative plates, source of radiation is CuK α 1, in angle of diffraction 2 θ values, be 5.33, 6.30, 7.66, 12.59, 13.99, 14.80, 17.21, 18.38, 19.72, 21.38, there is stronger diffraction peak at 24.18 places, in angle of diffraction 2 θ values, be 5.76, 8.72, 8.98, 9.34, 10.38, 10.64, 11.05, 11.49, 13.03, 13.76, 16.46, 17.78, 18.71, 20.09, 20.82, 22.13, 22.51, 23.07, 23.33, 23.67, 24.87, 25.33, 26.45, 27.64, 28.72, 29.20, 30.97, 31.4, 33.81, 34.82, 36.48, there is weak diffraction peak at 37.11 places, wherein 2 θ value limit of error are ± 0.2.
2. pantoprazole sodium crystal W as claimed in claim 1, is characterized in that DSC collection of illustrative plates has endotherm(ic)peak at 167 ± 5 ℃.
3. pantoprazole sodium crystal W according to claim 1, described PXRD collection of illustrative plates as shown in Figure 1 and/or described DSC collection of illustrative plates as shown in Figure 2.
4. pantoprazole sodium crystal W according to claim 1, its preparation method is: under room temperature, by Pantoprazole Sodium times semihydrate stirring suspension in Isosorbide-5-Nitrae-dioxane, filter.
5. the preparation method of pantoprazole sodium crystal W: by Pantoprazole Sodium times semihydrate stirring suspension in Isosorbide-5-Nitrae-dioxane, filter under room temperature.
6. a pantoprazole sodium crystal Y, in its PXRD collection of illustrative plates, source of radiation is CuK α 1, in angle of diffraction 2 θ values, be that 6.71,15.77,20.13,20.85,23.25,23.53,27.65,29.25 places have stronger diffraction peak, in angle of diffraction 2 θ values, be that 13.28,13.76,17.15,18.99,21.57,24.75,25.72,26.39,26.65,32.17,32.65,33.84,36.18,37.27,41.04,43.68 places have weak diffraction peak, wherein 2 θ value limit of error are ± 0.2.
7. pantoprazole sodium crystal Y as claimed in claim 5, is characterized in that DSC collection of illustrative plates has endotherm(ic)peak at 140 ± 5 ℃.
8. pantoprazole sodium crystal Y according to claim 5, described PXRD collection of illustrative plates as shown in Figure 3 and/or described DSC collection of illustrative plates as shown in Figure 4.
9. according to the pantoprazole sodium crystal Y described in claim 5 or 6, its preparation method: under room temperature, a Pantoprazole Sodium times semihydrate is dissolved in tetrahydrofuran (THF), after filtering that filtrate is standing, slowly volatilization is taken out solid, with 1 after solvent all volatilizes, the drip washing of 4-dioxane.
10. the preparation method of a pantoprazole sodium crystal Y: under room temperature, a Pantoprazole Sodium times semihydrate is dissolved in tetrahydrofuran (THF), after filtering that filtrate is standing, slowly volatilization is taken out solid after solvent all volatilizes, with the drip washing of Isosorbide-5-Nitrae-dioxane.
11. 1 kinds of pantoprazole sodium crystal Z, in its PXRD collection of illustrative plates, source of radiation is CuK α 1, in angle of diffraction 2 θ values, be 5.43, 11.84, 12.93, 13.58, 15.26, 16.21, 16.42, 18.20, 21.65, 25.01, 25.82, there is stronger diffraction peak at 26.27 places, in angle of diffraction 2 θ values, be 10.36, 14.27, 17.35, 19.13, 19.54, 20.41, 21.32, 21.95, 22.90, 23.12, 23.79, 24.55, 25.42, 27.38, 27.71, 28.13, 28.37, 29.65, 29.92, 32.02, 32.98, 33.36, 33.79, 34.52, 35.00, 35.97, 37.07, 39.70, there is weak diffraction peak at 40.48 places, wherein 2 θ value limit of error are ± 0.2.
12. pantoprazole sodium crystal Z as claimed in claim 9, is characterized in that DSC collection of illustrative plates has two endotherm(ic)peaks at 76 ± 5 ℃, 157 ± 5 ℃.
13. pantoprazole sodium crystal Z according to claim 9, described PXRD collection of illustrative plates as shown in Figure 5 and/or described DSC collection of illustrative plates as shown in Figure 6.
14. according to the pantoprazole sodium crystal Z described in claim 9 or 10, and its preparation method is: under room temperature, a Pantoprazole Sodium times semihydrate is dissolved in 2-butanone, and after filtering that filtrate is standing, slowly evaporate into crystallize out, filter.
The preparation method of 15. 1 kinds of pantoprazole sodium crystal Z: under room temperature, a 1 g Pantoprazole Sodium times semihydrate is dissolved in 2-butanone, after filtering that filtrate is standing, slowly volatilization, crystallize out in solution after 1 ~ 3 day, filters.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104856994A (en) * | 2015-05-26 | 2015-08-26 | 苗怡文 | Medical pantoprazole sodium composition tablet for treating gastric ulcer |
| CN104958265A (en) * | 2015-08-05 | 2015-10-07 | 青岛蓝盛洋医药生物科技有限责任公司 | Medicinal pantoprazole sodium composition granules for treating digestive system diseases |
| WO2016127684A1 (en) * | 2015-02-12 | 2016-08-18 | 天津大学 | New crystal form of pantoprazole sodium compound and preparation method therefor |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040186139A1 (en) * | 2002-09-02 | 2004-09-23 | Dr. Reddy's Laboratories Limited | Process for preparation of crystalline form-1 of pantoprazole sodium sesquihydrate |
| WO2004099183A1 (en) * | 2003-05-06 | 2004-11-18 | Hetero Drugs Limited | Novel polymorphs of pantoprazole sodium |
| WO2007091276A2 (en) * | 2006-02-10 | 2007-08-16 | Rajasthan Antibiotic Limited | Novel crystal form of omeprazol sodium |
-
2013
- 2013-10-11 CN CN201310472625.3A patent/CN103709140A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040186139A1 (en) * | 2002-09-02 | 2004-09-23 | Dr. Reddy's Laboratories Limited | Process for preparation of crystalline form-1 of pantoprazole sodium sesquihydrate |
| WO2004099183A1 (en) * | 2003-05-06 | 2004-11-18 | Hetero Drugs Limited | Novel polymorphs of pantoprazole sodium |
| WO2007091276A2 (en) * | 2006-02-10 | 2007-08-16 | Rajasthan Antibiotic Limited | Novel crystal form of omeprazol sodium |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016127684A1 (en) * | 2015-02-12 | 2016-08-18 | 天津大学 | New crystal form of pantoprazole sodium compound and preparation method therefor |
| CN104856994A (en) * | 2015-05-26 | 2015-08-26 | 苗怡文 | Medical pantoprazole sodium composition tablet for treating gastric ulcer |
| CN104958265A (en) * | 2015-08-05 | 2015-10-07 | 青岛蓝盛洋医药生物科技有限责任公司 | Medicinal pantoprazole sodium composition granules for treating digestive system diseases |
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Application publication date: 20140409 |