CN103980261A - Canagliflozin of crystal form A, and crystallization preparation method thereof - Google Patents
Canagliflozin of crystal form A, and crystallization preparation method thereof Download PDFInfo
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- CN103980261A CN103980261A CN201410129786.7A CN201410129786A CN103980261A CN 103980261 A CN103980261 A CN 103980261A CN 201410129786 A CN201410129786 A CN 201410129786A CN 103980261 A CN103980261 A CN 103980261A
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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
Abstract
The invention discloses a canagliflozin of crystal form A, and a crystallization preparation method thereof. The X-ray powder diffraction pattern of the canagliflozin of crystal form A has characteristic peaks at diffraction angles 2theta with the values of 3.7+/-0.1, 3.9+/-0.1, 7.7+/-0.1, 7.9+/-0.1, 11.5+/-0.1, 13.1+/-0.1, 13.5+/-0.1, 14.3+/-0.1, 15.5+/-0.1, 17.3+/-0.1, 18.8+/-0.1, 19.3+/-0.1, 20.3+/-0.1, 22.5+/-0.1, 22.7+/-0.1, 23.2+/-0.1 and 23.4+/-0.1. The preparation method has the advantages of simplicity and easy operation of operation steps, short time and less energy consumption. The above product prepared in the invention has a good stability, high a purity of above 99%, and has a yield of about 90%, and the purity, the color and the form of the product are unchanged after the product is stored under normal temperature dry conditions for 100d.
Description
Technical field
The invention belongs to fine chemistry industry and application, particularly clean new crystal and the crystallization preparation method thereof of a kind of Ka Gelie.
Background technology
Chemistry 1-(β-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienyl methyl by name of Ka Gelie clean (canagliflozin)] benzene, molecular formula is C
24h
25fO
5s, molecular weight is 444.52, structural formula is suc as formula (I).Ka Gelie is only as a kind of sodium dependent glucose running albumen (SGLT) inhibitor, food and drug administration (FDA) ratifies its tablet and coordinates with diet and motion on March 29th, 2013, it can make glucose in uriniferous tubules heavily not absorb smoothly to enter blood and discharge with urine, thereby reduction blood sugar concentration, controls blood sugar for adults with type 2 diabetes.
Diabetes are a kind of global chronic diseases that perplex, and at present approximately there are 2.3 hundred million patients in the whole world, and are the multiple phases of diabetes B after 35-40 year, make a definite diagnosis diabetic subject and account for more than 90%.Long-term hyperglycemia can increase the risk that occurs severe complication, comprises heart trouble, blind, nerve and kidney damage.Along with the sickness rate in growth in the living standard children also has the trend of rising in recent years.Reported that hyperglycemia is relevant with the damage of carrying out property with the morbidity of diabetes, chronic hyperglycemia can cause insulin secretion to reduce and further reduce insulin sensitivity, and result causes blood sugar concentration to increase so that diabetes self worsen.Therefore, by treatment hyperglycemia, thereby capable of blockingly above-mentionedly self worsen circulation and make prevention and treatment diabetes become possibility.
Although dietetic treatment and exercise therapy are essential in the treatment of diabetes, when these therapies are not enough to control illness, need other insulin injection or oral antidiabetic thing.At present, as antidiabetic, have: biguanide compound, sulphonyl urea compound, Regular Insulin impedance activator and alpha-glucosidase inhibitor.Yet these antidiabetics have various side effects.For example, biguanide compound can cause that lactic acidosis, sulphonyl urea compound can cause that hypoglycemia, Regular Insulin impedance activator can cause oedema, cardiac failure significantly, and alpha-glucosidase inhibitor can cause abdominal distension and diarrhoea.In this case, need to develop the new drug that is used for the treatment of diabetes and does not there are these side effects.
As one of method for the treatment of hyperglycemia, medically make excessive glucose can directly drain in urine and make blood sugar concentration normalizing.For example, the sodium dependent glucose running albumen that is positioned at kidney near-end kidney convoluted tubule by inhibition can suppress kidney to the absorbing again of glucose, promotes by this glucose to drain and into urine, makes glucose level reduce.In fact, confirmed that to the continuous subcutaneous administration of diabetes animal model, having SGLT suppresses active phlorizin, can make hyperglycemia normalizing and its glucose level is maintained normally in a long time, thereby improve insulin secretion and insulin resistant.
It is solid that Ka Gelie purifies under compound normal temperature and pressure, and it is first disclosed as in Chinese patent CN200480022007.8, and by day Honda limit, Co., Ltd. proposes.Its commodity are called Invokana(canagliflozin) tablet, by the Janssen Pharmaceutica of New Jersey Titusville, manufactured.Invokana tablet coordinates diet and motion to control blood sugar for adults with type 2 diabetes.Invokana kidney capable of blocking absorbs, increases glucose to glucose and drains and reduce blood sugar in diabetic patients level.Invokana can not increase (diabetic ketoacidosis) or severe renal functional defect, whole latter stage nephropathy or at dialysis patients for type 1 diabetes, blood urine ketone.
Patent CN200780043154.7, WO2008069327A1 disclose Ka Gelie clean semihydrate crystal formation and crystallization method thereof, this crystallization method crystallization time is longer, generally more than 20 hours.
Patent CN200880106239.X, WO2012154812A1 disclose clean compound crystal formation and the crystallization method thereof of Ka Gelie, and the crystallization method step of describing in the document is more, and need under the condition of argon shield, carry out.
It is clean clean with eutectic and the amorphous Ka Gelie of L-PROLINE, D-PROLINE, L-Phe that patent WO2013064909A2 discloses Ka Gelie, and this patent is mainly eutectic and the crystallization method thereof of clean and other the various assistant agents formation of the Ka Gelie that describes.
Summary of the invention
The invention discloses a kind of crystal formation of the new clean crystal of Ka Gelie, its X-ray powder diffraction is in diffraction angle 2 θ=3.7 ± 0.1,3.9 ± 0.1,7.7 ± 0.1,7.9 ± 0.1,11.5 ± 0.1,13.1 ± 0.1,13.5 ± 0.1,14.3 ± 0.1,15.5 ± 0.1,17.3 ± 0.1,18.8 ± 0.1,19.3 ± 0.1,20.3 ± 0.1,22.5 ± 0.1, there is characteristic peak at 22.7 ± 0.1,23.2 ± 0.1 and 23.4 ± 0.1 degree places, as shown in Figure 1; Ka Gelie is clean for called after A crystal formation.XRD figure spectrum is to collect X-ray powder diffraction instrument (D/max-2500, Rigaku Rigaku) is upper, and its transmitting target is Cu/K α, and power supply is set to 40kV/100mA, scanning speed be 2 degree/minute, scanning step is 0.02 degree, 2 θ sweep limits are 2 degree to 40 degree.
The described clean crystal of A crystal formation Ka Gelie, its dsc analysis result shows, has a feature endotherm(ic)peak, as shown in Figure 2 at 105 ± 2 ℃.DSC data are obtained by differential scanning calorimeter (DSC1/500, Switzerland Mettler Toledo company) analysis, and analysis condition is: sample 5~10mg is placed in aluminium crucible, in high-purity N
2under protection, with the speed of 2 ℃/min, sample temperature is risen to 125 ℃ by 25 ℃.
The profile of the described clean crystal of A crystal formation Ka Gelie is as shown in Fig. 3 microphotograph.Crystal boundary microphotograph is observed and is recorded by polarizing microscope (OLYMPUS BX51, MicroPublisher5.0RTU) and obtains.
The preparation method of the clean crystal of A crystal formation Ka Gelie of the present invention is as follows:
The clean crude product of Ka Gelie is added in alcoholic solvent, be mixed with the suspension of 0.05~0.5g/mL, under stirring action, at 15~43 ℃, solid is dissolved completely, in solution, drip dissolved agent, dissolved agent consumption is 3~10 times of alcoholic solvent volume; The formed suspension of suction filtration, obtains the clean crystal product of A crystal formation Ka Gelie after being dried.
The purity of the described clean crude product of Ka Gelie is 92.0%~96.0%.
Described alcoholic solvent is selected from one or more the mixed solvent in methyl alcohol, ethanol, propyl carbinol, isopropylcarbinol, sec-butyl alcohol, n-propyl alcohol, Virahol, ethylene glycol, Pentyl alcohol or primary isoamyl alcohol.
Described dissolved agent is selected from one or more the mixed solution in normal heptane, normal hexane, hexanaphthene, octane, n-butyl ether, sherwood oil, ether or water.
In described method, the drop rate of dissolved agent is 0.2%~5% of per minute dropping dissolved agent volume.
In described method, drying conditions is to carry out 6~8h under 30~65 ℃, the condition of normal pressure.
The inventive method has following beneficial effect:
The dilution crystallization method operation steps that adopts is simple to operation, consuming time short, power consumption is few.The product stability of preparing is good, purity higher than 99%, yield 90% left and right, product stored after 100 days under normal temperature, drying conditions, product purity, color, form do not change.Product is easy to pulverize and be easy to add the formulation of pharmaceutical composition, and cost is low, is easier to commercial industries scale and implements.
Only as Ka Gelie, clean selecting provides a new crystal formation to A crystal formation Ka Gelie, and the application of Ka Gelie is provided more choices.
Described A crystal formation Ka Gelie is applied to the raw material of the effective constituent of 1 type and diabetes B, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, postprandial hyperglycemia disease, hyperinsulinemia only.
Accompanying drawing explanation
Fig. 1: the X-ray powder diffraction pattern of the clean crystal of A crystal formation Ka Gelie;
Fig. 2: the dsc analysis figure of the clean crystal of A crystal formation Ka Gelie;
Fig. 3: the microphotograph of the clean crystal of A crystal formation Ka Gelie.
Embodiment
Embodiment 1:
The clean solid 5.1g of Ka Gelie dry, purity 92.0% is added in 100mL n-propyl alcohol and forms suspension, under agitation this suspension is heated to 15 ℃, solid is all dissolved; With the speed of 0.6mL/min, to the hexanaphthene that drips 300mL in solution, obtain suspension, vacuum filtration magma, by product under 30 ℃, normal pressure dry 8 hours to constant weight, obtain A crystal formation Ka Gelie net products.As shown in Figure 1, it is in diffraction angle 2 θ=3.71,3.94,7.77 for the X-ray powder diffraction of product, 7.92,11.53,13.16,13.58,14.30,15.56,17.32,18.81,19.36,20.31,22.50,22.79,23.24, there is characteristic peak at 23.48 degree places, and dsc analysis figure is as Fig. 2, and it has feature endotherm(ic)peak at 105.4 ℃.Crystal boundary microphotograph as shown in Figure 3.
The A crystal formation Ka Gelie net products good stability preparing, purity 99.3%, yield 88.3%, product stored after 100 days under normal temperature, drying conditions, and product purity, color, form do not change.Product is easy to pulverize and be easy to add the formulation of pharmaceutical composition.
Embodiment 2:
The clean solid 14.3g of Ka Gelie dry, purity 96.0% is added in 100mL Virahol and forms suspension, under agitation this suspension is heated to 25 ℃, solid is all dissolved; With the speed of 5mL/min, to the mixing dissolved agent that drips the normal hexane of 400mL and the water of 100mL in solution, obtain suspension, vacuum filtration magma, by product under 45 ℃, normal pressure dry 7 hours to constant weight, obtain A crystal formation Ka Gelie clean.The X-ray powder diffraction of product is in diffraction angle 2 θ=3.73,3.96,7.78,7.94,11.53,13.15,13.57,14.31,15.58,17.34,18.82,19.35,20.32,22.52,22.79, there is characteristic peak at 23.25,23.48 degree places, and dsc analysis figure has located feature endotherm(ic)peak at 105.56 ℃.
The A crystal formation Ka Gelie net products good stability preparing, purity 99.1%, yield 89.6%, product stored after 100 days under normal temperature, drying conditions, and product purity, color, form do not change.Product is easy to pulverize and be easy to add the formulation of pharmaceutical composition.
Embodiment 3:
The clean solid 28.5g of Ka Gelie dry, purity 94.0% is added in 40mL ethanol and 60mL Pentyl alcohol and forms suspension, under agitation this suspension is heated to 38 ℃, solid is all dissolved; With the speed of 26mL/min, to the sherwood oil that drips 650mL in solution, obtain suspension, vacuum filtration magma is dried to constant weight in 6 hours by product under 45 ℃, normal pressure, obtains A crystal formation Ka Gelie clean.The X-ray powder diffraction of product is in diffraction angle 2 θ=3.74,3.96,7.77,7.95,11.55,13.17,13.58,14.32,15.59,17.36,18.82,19.36,20.33,22.53,22.78, there is characteristic peak at 23.25,23.48 degree places, and dsc analysis figure has located feature endotherm(ic)peak at 106.72 ℃.
The A crystal formation Ka Gelie net products good stability preparing, purity 99.2%, yield 90.5%, product stored after 100 days under normal temperature, drying conditions, and product purity, color, form do not change.Product is easy to pulverize and be easy to add the formulation of pharmaceutical composition.
Embodiment 4:
The clean solid 50.0g of Ka Gelie dry, purity 95.0% is added in 30mL n-propyl alcohol and 70mL methyl alcohol and forms suspension, under agitation this suspension is heated to 43 ℃, solid is all dissolved; With the speed of 50mL/min, to dripping the octane of 500mL in solution and the normal heptane of 500mL mixes dissolved agent, obtain suspension, vacuum filtration magma, by product under 65 ℃, normal pressure dry 6 hours to constant weight, obtain A crystal formation Ka Gelie clean.The X-ray powder diffraction of product is in diffraction angle 2 θ=3.72,3.94,7.76,7.95,11.54,13.16,13.57,14.32,15.58,17.35,18.81,19.35,20.33,22.53,22.77, there is characteristic peak at 23.24,23.47 degree places, and dsc analysis figure has located feature endotherm(ic)peak at 105.82 ℃.
The A crystal formation Ka Gelie net products good stability preparing, purity 99.1%, yield 91.2%, product stored after 100 days under normal temperature, drying conditions, and product purity, color, form do not change.Product is easy to pulverize and be easy to add the formulation of pharmaceutical composition.
Open and clean crystal of A crystal formation Ka Gelie of proposing of the present invention and preparation method thereof, those skilled in the art can be by using for reference content herein, and the links such as appropriate change raw material, processing parameter realize.Method of the present invention and product are described by preferred embodiment, person skilled obviously can be within not departing from content of the present invention, spirit and scope to method as herein described with product is changed or suitably change and combination, realize the technology of the present invention.Special needs to be pointed out is, all similar replacements and change apparent to those skilled in the artly, they are deemed to be included in spirit of the present invention, scope and content.
Claims (9)
1. the clean new crystal of Yi Zhong Ka Gelie, is characterized in that X-ray powder diffraction is in diffraction angle 2 θ=3.7 ± 0.1,3.9 ± 0.1,7.7 ± 0.1,7.9 ± 0.1,11.5 ± 0.1,13.1 ± 0.1,13.5 ± 0.1,14.3 ± 0.1,15.5 ± 0.1,17.3 ± 0.1,18.8 ± 0.1,19.3 ± 0.1,20.3 ± 0.1,22.5 ± 0.1, there is characteristic peak at 22.7 ± 0.1,23.2 ± 0.1 and 23.4 ± 0.1 degree places.
2. crystal formation as claimed in claim 1, is characterized by called after A crystal formation Ka Gelie clean.
3. crystal as claimed in claim 1, is characterized in that dsc analysis result shows, has a feature endotherm(ic)peak at 105 ± 2 ℃.
4. the preparation method of the clean crystal formation of Ka Gelie as claimed in claim 1, is characterized in that:
The clean crude product of Ka Gelie is added in alcoholic solvent, be mixed with the suspension of 0.05~0.5g/mL, under stirring action, at 15~43 ℃, solid is dissolved completely, in solution, drip dissolved agent, dissolved agent consumption is 3~10 times of alcoholic solvent volume; The formed suspension of suction filtration, obtains the clean new crystal of Ka Gelie after being dried.
5. method as claimed in claim 4, is characterized in that described alcoholic solvent is selected from one or more the mixed solvent in methyl alcohol, ethanol, propyl carbinol, isopropylcarbinol, sec-butyl alcohol, n-propyl alcohol, Virahol, ethylene glycol, Pentyl alcohol or primary isoamyl alcohol.
6. method as claimed in claim 4, is characterized in that described dissolved agent is selected from one or more the mixed solution in normal heptane, normal hexane, hexanaphthene, octane, n-butyl ether, sherwood oil, ether or water.
7. method as claimed in claim 4, the drop rate that it is characterized in that dissolved agent be per minute drip dissolved agent volume 0.2%~5%.
8. method as claimed in claim 4, is characterized in that described drying conditions is that temperature is to enter under 30~65 ℃, the condition of normal pressure
Row 6~8h.
9. the clean new crystal of Ka Gelie as claimed in claim 1, is characterized in that the raw material of the effective constituent of 1 type that is applied to and diabetes B, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, hyperglycemia, hyperinsulinemia.
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Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104530024A (en) * | 2015-02-04 | 2015-04-22 | 上海迪赛诺药业有限公司 | Crystal form of 1-(beta-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienyl methyl] benzene and preparation method thereof |
CN104530023A (en) * | 2014-12-25 | 2015-04-22 | 重庆医药工业研究院有限责任公司 | Crystal form I of Canagliflozin and preparation method thereof |
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CN105541818A (en) * | 2016-03-04 | 2016-05-04 | 浙江华海药业股份有限公司 | Novel crystal form of canagliflozin hydrate and preparation method of novel crystal form |
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US20180016290A1 (en) * | 2015-02-09 | 2018-01-18 | Indoco Remedies Limited | Process for the preparation of sglt inhibitor compounds |
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WO2018149327A1 (en) | 2017-02-20 | 2018-08-23 | 浙江华海药业股份有限公司 | Method for preparing canagliflozin amorphous form |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008069327A1 (en) * | 2006-12-04 | 2008-06-12 | Mitsubishi Tanabe Pharma Corporation | CRYSTALLINE FORM OF 1- (β-D-GLUCOPYRANOSYL) -4 -METHYL- 3- [5- (4 -FLUOROPHENYL) -2-THIENYLMETHYL] BENZENE HEMIHYDRATE |
WO2009035969A1 (en) * | 2007-09-10 | 2009-03-19 | Janssen Pharmaceutica N.V. | Process for the preparation of compounds useful as inhibitors of sglt |
CN102648196A (en) * | 2009-10-14 | 2012-08-22 | 詹森药业有限公司 | Process for the preparation of compounds useful as inhibitors of SGLT2 |
WO2012154812A1 (en) * | 2011-05-09 | 2012-11-15 | Janssen Pharmaceutica Nv | L-proline and citric acid co-crystals of (2s, 3r, 4r, 5s, 6r )- 2- (3- ((5- (4-fluorophenyl)thiophen-2-yl) methyl) -4-methylphenyl)-6- (hydroxymethyl)tetrahydro-2h-pyran-3,4,5-triol |
CN102985075A (en) * | 2010-05-11 | 2013-03-20 | 田边三菱制药株式会社 | Canagliflozin containing tablets |
WO2013064909A2 (en) * | 2011-10-31 | 2013-05-10 | Scinopharm Taiwan, Ltd. | Crystalline and non-crystalline forms of sglt2 inhibitors |
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 |
CN103596944A (en) * | 2011-04-13 | 2014-02-19 | 詹森药业有限公司 | Process for the preparation of compounds useful as inhibitors of SGLT2 |
CN103641822A (en) * | 2013-10-21 | 2014-03-19 | 江苏奥赛康药业股份有限公司 | Canagliflozin compound and pharmaceutical composition thereof |
-
2014
- 2014-04-01 CN CN201410129786.7A patent/CN103980261B/en not_active Expired - Fee Related
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008069327A1 (en) * | 2006-12-04 | 2008-06-12 | Mitsubishi Tanabe Pharma Corporation | CRYSTALLINE FORM OF 1- (β-D-GLUCOPYRANOSYL) -4 -METHYL- 3- [5- (4 -FLUOROPHENYL) -2-THIENYLMETHYL] BENZENE HEMIHYDRATE |
WO2009035969A1 (en) * | 2007-09-10 | 2009-03-19 | Janssen Pharmaceutica N.V. | Process for the preparation of compounds useful as inhibitors of sglt |
CN101801371A (en) * | 2007-09-10 | 2010-08-11 | 詹森药业有限公司 | The preparation method of the chemical compound of useful as inhibitors of sglt |
CN102648196A (en) * | 2009-10-14 | 2012-08-22 | 詹森药业有限公司 | Process for the preparation of compounds useful as inhibitors of SGLT2 |
CN102985075A (en) * | 2010-05-11 | 2013-03-20 | 田边三菱制药株式会社 | Canagliflozin containing tablets |
CN103596944A (en) * | 2011-04-13 | 2014-02-19 | 詹森药业有限公司 | Process for the preparation of compounds useful as inhibitors of SGLT2 |
WO2012154812A1 (en) * | 2011-05-09 | 2012-11-15 | Janssen Pharmaceutica Nv | L-proline and citric acid co-crystals of (2s, 3r, 4r, 5s, 6r )- 2- (3- ((5- (4-fluorophenyl)thiophen-2-yl) methyl) -4-methylphenyl)-6- (hydroxymethyl)tetrahydro-2h-pyran-3,4,5-triol |
WO2013064909A2 (en) * | 2011-10-31 | 2013-05-10 | Scinopharm Taiwan, Ltd. | Crystalline and non-crystalline forms of sglt2 inhibitors |
CN103641822A (en) * | 2013-10-21 | 2014-03-19 | 江苏奥赛康药业股份有限公司 | Canagliflozin compound and pharmaceutical composition thereof |
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 |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104974146A (en) * | 2014-09-15 | 2015-10-14 | 苏州晶云药物科技有限公司 | Crystal form E and crystal form F of canagliflozin and preparation method thereof |
CN104974146B (en) * | 2014-09-15 | 2018-02-02 | 苏州晶云药物科技有限公司 | Crystal formation E, crystal formation F of canagliflozin and preparation method thereof |
CN104530023A (en) * | 2014-12-25 | 2015-04-22 | 重庆医药工业研究院有限责任公司 | Crystal form I of Canagliflozin and preparation method thereof |
JP2018500368A (en) * | 2014-12-25 | 2018-01-11 | 重慶医薬工業研究院有限責任公司 | Canagliflozin crystal form I and process for producing the same |
CN108003149A (en) * | 2014-12-25 | 2018-05-08 | 重庆医药工业研究院有限责任公司 | A kind of canagliflozin crystal form I and preparation method thereof |
CN104530024A (en) * | 2015-02-04 | 2015-04-22 | 上海迪赛诺药业有限公司 | Crystal form of 1-(beta-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienyl methyl] benzene and preparation method thereof |
EP3053919A1 (en) | 2015-02-04 | 2016-08-10 | Shanghai Desano Pharmaceuticals Investment Co., Ltd | Crystalline form of 1-(beta-d-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene and preparation method thereof |
US10167306B2 (en) | 2015-02-04 | 2019-01-01 | Shanghai Desano Pharmaceuticals Investment Co., Ltd. | Crystalline form of 1-(beta-D-glucopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienylmethyl]benzene and preparation method thereof |
US20180016290A1 (en) * | 2015-02-09 | 2018-01-18 | Indoco Remedies Limited | Process for the preparation of sglt inhibitor compounds |
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CN108017626A (en) * | 2016-11-04 | 2018-05-11 | 上海奥博生物医药技术有限公司 | A kind of canagliflozin semihydrate novel crystal forms |
WO2018149327A1 (en) | 2017-02-20 | 2018-08-23 | 浙江华海药业股份有限公司 | Method for preparing canagliflozin amorphous form |
CN107311993A (en) * | 2017-08-09 | 2017-11-03 | 江苏德源药业股份有限公司 | A kind of crystal formation II of canagliflozin and preparation method thereof |
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