CN108017626A - A kind of canagliflozin semihydrate novel crystal forms - Google Patents
A kind of canagliflozin semihydrate novel crystal forms Download PDFInfo
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- CN108017626A CN108017626A CN201610964905.XA CN201610964905A CN108017626A CN 108017626 A CN108017626 A CN 108017626A CN 201610964905 A CN201610964905 A CN 201610964905A CN 108017626 A CN108017626 A CN 108017626A
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- canagliflozin
- crystal form
- semihydrate
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- crystal forms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of novel crystal forms of canagliflozin (1 (β D glycopyranosyls) 4 methyl 3 [5 (4 fluorophenyl) 2 thienyl methyls] benzene) semihydrate, about 3.8 in the X-ray powder diffraction pattern that the canagliflozin semihydrate novel crystal forms are detected using Cu K α radiations, 7.7,11.6,15.5,19.4,23.3,27.3,31.3 (± 0.2) degree has characteristic peak.
Description
Technical field
The present invention relates to a kind of canagliflozin (1- (β-D- glycopyranosyls) -4- methyl -3- [5- (4- fluorophenyls) -2- thiophenes
Fen ylmethyl] benzene) semihydrate novel crystal forms, belong to chemical medicine.
Technical background
Entitled 1- (β-D- glycopyranosyls) -4- methyl -3- [5- (the 4- fluorobenzene of canagliflozin (Canagliflozin) chemistry
Base) -2- thienyl methyls] benzene is Janssen Pharmaceutica of the subsidiary exploitation by Johson ＆ Johnson.Canagliflozin is a selectivity
2 type sodium glucose transporter (SGLT-2) inhibitor, can specificity suppress reabsorption of the kidney to glucose, make excessive Portugal
Grape sugar is discharged from urine, so as to directly reduce blood sugar level.The medicine obtains FDA approvals on March 29th, 2013 and is used to treat
Type ii diabetes.
It is well known that polymorphism is widely present in medicine.In recent years, the polymorphism of drug molecule is increasingly
Attract much attention.Since different polycrystalline kenels is in solubility, fusing point, dissolution rate, stability, biological effectiveness etc.
There is very big difference, cause the different crystal forms of same medicine to produce different influences in bioavilability and curative effect.Therefore, medicine
It is necessary to carry out comprehensive and systematic screening polymorph in thing research and development, selects to be most suitable for the crystal form of exploitation.
Patent CN101573368B discloses the semihydrate crystal form and its method for crystallising of canagliflozin, which finally uses
In industrialization.Having patent to mention, the crystal form crystal grain that this method is prepared is small, and electrostatic is big, to preparing pharmaceutical formulation by certain
Counter productive.
Patent CN103554092A discloses the crystal form B of canagliflozin, is volatilized from the in the mixed solvent of second alcohol and water
Arrive.
Patent CN104356122A disclose canagliflozin crystal form C and crystal form D and preparation method thereof.In specification not
Illustrate any substantial advantage compared with the prior art discloses crystal form.
Patent CN103889429A disclose canagliflozin and L-PROLINE, D-PROLINE, L-phenylalanine eutectic with
And amorphous canagliflozin, the patent are mainly the eutectic and its crystallization side that the canagliflozin described is formed with other various assistant agents
Method.
Patent CN103980261A and CN103980262A discloses the A crystal forms and B crystal form of canagliflozin.Disclosed by patent
Data understand, A, B crystal form is long laminated structure, has poor mobility, and there are query for repeatability.
Patent WO 2014180872 discloses a kind of new canagliflozin hydrate crystal forms, which contains
Water is non-chemical dose, and crystal form feature can not determine completely, so it is difficult to ensure that can be made in large-scale production process
It is standby go out the consistent crystal form of product quality.
In conclusion the crystal form of canagliflozin develops the novel crystal forms of canagliflozin, after being there are various technical problems at present
It is very necessary that the exploitation of continuous medicine provides new selection.The present inventor has found a kind of new canagliflozin by constantly studying
Semihydrate crystal form, overcomes problem existing in the prior art.
The content of the invention
The present invention provides the solid form of canagliflozin semihydrate (type I compound) novel crystal forms E, named in the present invention
For crystal form E.
Further, the present invention provides the solid form of canagliflozin semihydrate (type I compound), its feature to exist
In the X-ray powder diffraction pattern of the semihydrate crystal form E includes the characteristic peak shown in following 2 θ angles：3.8,7.7,
11.6,15.5,19.4,23.3,27.3,31.3 (± 0.2)；(such as Fig. 1)
Further, the present invention provides the solid form of canagliflozin semihydrate (type I compound), its feature to exist
In the Differential Scanning Calorimetry of the semihydrate crystal form E, which is shown at about 99-107 DEG C, endothermic peak；(such as Fig. 2)
Further, the present invention provides the solid form of canagliflozin semihydrate (type I compound), its feature to exist
In the semihydrate crystal form E shows about 1.5%-1.7% weightlessness by thermogravimetric analysis.(such as Fig. 3)
Brief description of the drawings
Fig. 1 is the XRPD spectrograms of canagliflozin semihydrate crystal form E.
Fig. 2 is the DSC spectrograms of canagliflozin semihydrate crystal form E.
Fig. 3 is the TGA spectrograms of canagliflozin semihydrate crystal form E.
Example is embodied：
Elaborate below with reference to embodiment to embodiments of the present invention.Embodiments of the present invention are included but not
Following embodiments are confined to, it is not construed as limiting the scope of the invention.
X-ray powder diffraction data of the present invention are the BRUKER D8Advance using German Brooker company
Measure, voltage and current：40kV,40mA；Angular instrument：Vertical angular instrument, radius 280mm；Slit：DS=2 °, SS=1/2 °,
Mask=15mm, RS=5.0mm；Detector：LYNXEYE detectors；Scan pattern：Continuous scanning；Scanning range：3-40°；Often
Walk gate time：0.2s；Scan total time：390s.
Differential Scanning Calorimetry of the present invention is measured using the Q2000 of TA companies of the U.S., temperature range 40-
295 DEG C, 10 DEG C/min of programming rate.
Thermogravimetric collection of illustrative plates of the present invention is measured using the Q500 of TA companies of the U.S., 10 DEG C/min of programming rate.
Embodiment 1：The preparation of canagliflozin semihydrate crystal form E
At room temperature, 80mg canagliflozins are weighed, add 3ml acetonitrile solutions, stirs to being completely dissolved, filters at room temperature.To
The water of 10.5ml is added dropwise in filtrate, solid separates out, white suspension.Solid is filtered after suspension is stood 3 days, is dry,
Obtain canagliflozin semihydrate crystal form E.
Embodiment 2：The preparation of canagliflozin semihydrate crystal form E
At room temperature, 80mg canagliflozins are weighed, add 3ml acetonitrile solutions, stirs to being completely dissolved, filters at room temperature.To
The water of 10.5ml is added dropwise in filtrate, adds 0.5mg canagliflozin semihydrate crystal forms E immediately as crystal seed.Solid separates out, in white
Color suspension.Solid is filtered after suspension is stood 3 days, is dry, obtains canagliflozin semihydrate crystal form E.
Embodiment 3：The preparation of canagliflozin semihydrate crystal form E
At room temperature, 320mg canagliflozins are weighed, add 12ml acetonitrile solutions, stirs to being completely dissolved, filters at room temperature.
The water of 42ml is added dropwise into filtrate, adds 10mg canagliflozin semihydrate crystal forms E as crystal seed.Solid separates out, white outstanding
Turbid.Solid is filtered after suspension is stood 3 days, is dry, obtains canagliflozin semihydrate crystal form E.
Claims (6)
- A kind of 1. crystal form E of canagliflozin semihydrate (Formulas I), it is characterised in that the X-ray powder diffraction pattern of the crystal form E Include the characteristic peak shown in following 2 θ angles：3.8,7.7,11.6,15.5,19.4,23.3,27.3,31.3 (± 0.2).
- 2. the crystal form E of canagliflozin semihydrate (Formulas I) as claimed in claim 1, it is characterised in that it has such as the institute of attached drawing 1 The X powder diffraction collection of illustrative plates shown.
- 3. the crystal form E of canagliflozin semihydrate (Formulas I) as claimed in claim 1, it is characterised in that pass through differential scanning amount Calorimetry analysis, which is shown at about 99-107 DEG C, endothermic peak.
- 4. the crystal form E of canagliflozin semihydrate (Formulas I) as claimed in claim 1, it is characterised in that it has such as the institute of attached drawing 2 The DSC collection of illustrative plates shown.
- 5. the crystal form E of canagliflozin semihydrate (Formulas I) as claimed in claim 1, it is characterised in that shown by thermogravimetric analysis It is shown with about 1.5%-1.7% weightlessness.
- 6. the crystal form E of canagliflozin semihydrate (Formulas I) as claimed in claim 1, it is characterised in that it has such as the institute of attached drawing 2 The TGA collection of illustrative plates shown.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610964905.XA CN108017626A (en) | 2016-11-04 | 2016-11-04 | A kind of canagliflozin semihydrate novel crystal forms |
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|---|---|---|---|
| CN201610964905.XA CN108017626A (en) | 2016-11-04 | 2016-11-04 | A kind of canagliflozin semihydrate novel crystal forms |
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| CN108017626A true CN108017626A (en) | 2018-05-11 |
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| CN201610964905.XA Pending CN108017626A (en) | 2016-11-04 | 2016-11-04 | A kind of canagliflozin semihydrate novel crystal forms |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111057049A (en) * | 2019-11-18 | 2020-04-24 | 杭州华东医药集团新药研究院有限公司 | Preparation method of canagliflozin hemihydrate |
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| CN101573368A (en) * | 2006-12-04 | 2009-11-04 | 田边三菱制药株式会社 | Crystalline form of 1- (belta-D-glucopyranosyl) -4 -methyl- 3- [5- (4 -fluorophenyl) -2-thienylmethyl] benzene hemihydrate |
| CN102482250A (en) * | 2009-07-10 | 2012-05-30 | 詹森药业有限公司 | Crystallisation process for 1-(ss-d-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl] benzene |
| CN103554092A (en) * | 2013-11-11 | 2014-02-05 | 苏州晶云药物科技有限公司 | New crystal form B of 1-(beta-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl] benzene and preparation method of new crystal form B |
| CN103980262A (en) * | 2014-04-01 | 2014-08-13 | 天津大学 | Canagliflozin of crystal form B, and crystallization preparation method thereof |
| CN103980261A (en) * | 2014-04-01 | 2014-08-13 | 天津大学 | Canagliflozin of crystal form A, and crystallization preparation method thereof |
| CN104356122A (en) * | 2013-11-27 | 2015-02-18 | 苏州晶云药物科技有限公司 | New crystal form of canagliflozin and preparation method thereof |
| CN104744449A (en) * | 2015-03-21 | 2015-07-01 | 北京工业大学 | Preparation method of canagliflozin hemihydrate and monocrystal thereof |
| WO2016016774A1 (en) * | 2014-07-31 | 2016-02-04 | Sun Pharmaceutical Industries Limited | Crystalline forms of canagliflozin |
| CN105358553A (en) * | 2013-05-08 | 2016-02-24 | 斯洛文尼亚莱柯制药股份有限公司 | Novel crystalline hydrates of 1-([beta]-d-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene |
-
2016
- 2016-11-04 CN CN201610964905.XA patent/CN108017626A/en active Pending
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101573368A (en) * | 2006-12-04 | 2009-11-04 | 田边三菱制药株式会社 | Crystalline form of 1- (belta-D-glucopyranosyl) -4 -methyl- 3- [5- (4 -fluorophenyl) -2-thienylmethyl] benzene hemihydrate |
| CN102482250A (en) * | 2009-07-10 | 2012-05-30 | 詹森药业有限公司 | Crystallisation process for 1-(ss-d-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl] benzene |
| CN105358553A (en) * | 2013-05-08 | 2016-02-24 | 斯洛文尼亚莱柯制药股份有限公司 | Novel crystalline hydrates of 1-([beta]-d-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene |
| CN103554092A (en) * | 2013-11-11 | 2014-02-05 | 苏州晶云药物科技有限公司 | New crystal form B of 1-(beta-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl] benzene and preparation method of new crystal form B |
| CN104356122A (en) * | 2013-11-27 | 2015-02-18 | 苏州晶云药物科技有限公司 | New crystal form of canagliflozin and preparation method thereof |
| CN103980262A (en) * | 2014-04-01 | 2014-08-13 | 天津大学 | Canagliflozin of crystal form B, and crystallization preparation method thereof |
| CN103980261A (en) * | 2014-04-01 | 2014-08-13 | 天津大学 | Canagliflozin of crystal form A, and crystallization preparation method thereof |
| WO2016016774A1 (en) * | 2014-07-31 | 2016-02-04 | Sun Pharmaceutical Industries Limited | Crystalline forms of canagliflozin |
| CN104744449A (en) * | 2015-03-21 | 2015-07-01 | 北京工业大学 | Preparation method of canagliflozin hemihydrate and monocrystal thereof |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111057049A (en) * | 2019-11-18 | 2020-04-24 | 杭州华东医药集团新药研究院有限公司 | Preparation method of canagliflozin hemihydrate |
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Application publication date: 20180511 |