CN103980262B - The B crystal form of canagliflozin and crystallization preparation method thereof - Google Patents
The B crystal form of canagliflozin and crystallization preparation method thereof Download PDFInfo
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Abstract
The invention discloses the B crystal form of a kind of canagliflozin and crystallization preparation method thereof, X-ray powder diffraction is in the angle of diffraction 2 θ=3.4 ± 0.1,6.6 ± 0.1,12.6 ± 0.1,13.2 ± 0.1,15.3 ± 0.1,15.6 ± 0.1,16.5 there is characteristic peak at ± 0.1,19.4 ± 0.1,19.8 ± 0.1 and 23.7 ± 0.1 degree of places。The inventive method has the advantages that operation efficient, easy, consuming time short。The B crystal form canagliflozin Crystal solubility prepared is bigger, rate of dissolution faster, the purity of product higher than 99%, yield about 95%, after product stores 100 days under room temperature, drying condition, product purity, color, form do not change。Product is prone to pulverize and be prone to add the dosage form of pharmaceutical composition, and cost is low, it is easier to commercial industries scale is implemented。
Description
Technical field
The invention belongs to fine chemistry industry and application, particularly to novel crystal forms and the crystallization preparation method thereof of a kind of canagliflozin。
Background technology
The chemistry of canagliflozin (canagliflozin) is called 1-(β-D-glycopyranosyl)-4-methyl-3-[5-(4-fluorophenyl)-2-thienyl methyl] benzene, and molecular formula is C24H25FO5S, molecular weight is 444.52, and structural formula such as formula is as follows。Canagliflozin is a kind of sodium dependent glucose operating albumen (SGLT) inhibitor, ratifies its tablet food and drug administration on March 29 in 2013 (FDA) and coordinates with diet and motion, controls blood glucose for adults with type 2 diabetes。
Long term hyperglycemia can increase risk severe complication occur, including heart disease, blind, neural and kidney damage。Along with in growth in the living standard child, the sickness rate of diabetes also has the trend of rising in recent years。Diabetes are a kind of chronic diseases perplexing the whole world, and type 2 diabetes mellitus is most common disease, how 35-40 year sequela, make a definite diagnosis diabetics and account for more than 90%。Although Diet Therapy and exercise therapy are required in the treatment of diabetes, but when these therapies are not enough to control disease, then need other insulin injection or oral antidiabetic thing。
In recent years, reported that hyperglycemia is relevant with the morbidity of diabetes and Progressive symmetric erythrokeratodermia damage, i.e. glucose toxicity theory。Reducing it is to say, chronic hyperglycemia may result in insulin secretion and reduce insulin sensitivity further, resulting in blood sugar concentration increases so that diabetes are self-exacerbated。Therefore, by treating hyperglycemia, above-mentioned self-exacerbating cycle can be blocked so that prevention and treatment diabetes are possibly realized。One of method as treatment hyperglycemia, it is considered to make excessive glucose directly to drain and make blood sugar concentration normalization in urine。Such as, by suppressing the sodium dependent glucose operating albumen being positioned at renal proximal kidney convoluted tubule can suppress the kidney re-absorption to glucose, thereby promote that glucose is drained and make into urine blood sugar level reduce。It is true that have proven to the phlorhizin to the continuous subcutaneous administration of diabetes animal model with SGLT inhibitory activity, hyperglycemia normalization can be made and make its blood sugar level remain normal in a long time, thus improving insulin secretion and insulin resistant。
At present, have as diabetes medicine: biguanide compound, sulphonyl urea compound, insulin resistance improving agent and alpha-glucosidase inhibitor。But, these antidiabetic medicines have various side effect。Such as, biguanide compound can cause lactic acidosis, sulphonyl urea compound that significant hypoglycemia, insulin resistance improving agent can be caused to cause edema, heart failure, and alpha-glucosidase inhibitor can cause abdominal distention and diarrhoea。It is thus desirable to develop for treating diabetes and not there is the new drug of these side effect。
Canagliflozin is first SGLT2(sodium-glucose co-transporters body 2 that food and drug administration (FDA) ratifies) inhibitor。It can make the glucose in renal tubules can not heavily be absorbed into blood smoothly and discharge with urine, thus reducing blood sugar concentration, is used for treating adult's type 2 diabetes mellitus。
Being solid under canagliflozin compound normal temperature and pressure, it is first disclosed as in Chinese patent CN200480022007.8, day Honda limit Co., Ltd. find。Its commodity are called Invokana(canagliflozin) tablet, the Janssen Pharmaceutica of New Jersey Titusville manufacture。Invokana tablet coordinates diet and motion to control blood glucose for adults with type 2 diabetes。Invokana can block kidney and glucose re-absorption, increase glucose are drained and reduce blood sugar in diabetic patients level。
Patent CN200780043154.7, WO2008069327A1 disclose canagliflozin semihydrate crystal formation and method for crystallising, this method for crystallising crystallization time is longer, is typically in more than 20 hours。
Patent CN200880106239.X, WO2012154812A1 disclose compound crystal form and the method for crystallising thereof of canagliflozin, and the method for crystallising step described in the document is more, and need to carry out when argon shield。
Patent WO2013064909A2 discloses canagliflozin and L-PROLINE, D-PROLINE, the eutectic of L-phenylalanine and amorphous canagliflozin, eutectic that the canagliflozin that this patent mainly describes and other various adjuvant are formed and method for crystallising thereof。
Summary of the invention
The invention discloses the crystal formation of a kind of new canagliflozin crystal, its X-ray powder diffraction in the angle of diffraction 2 θ=3.4 ± 0.1,6.6 ± 0.1,12.6 ± 0.1,13.2 ± 0.1,15.3 ± 0.1,15.6 ± 0.1,16.5 ± 0.1,19.4 ± 0.1,19.8 there is characteristic peak at ± 0.1 and 23.7 ± 0.1 degree of place, as it is shown in figure 1, called after B crystal form canagliflozin。XRD figure spectrum is that it launches target is Cu/K α, and power supply is set to 40kV/100mA, sweep speed 2 degree min, scanning step 0.02 degree, and 2 θ sweep limitss are 2 degree to 40 degree in the upper collection of X-ray powder diffractometer (D/max-2500, Rigaku Rigaku)。
Described B crystal form canagliflozin crystal, its dsc analysis result shows, has an endothermic peak at 84 ± 2 DEG C, as shown in Figure 2。DSC data is to obtain in the upper analysis of differential scanning calorimeter (DSC1/500, MettlerToledo company of Switzerland), and its analysis condition is: be placed in aluminum crucible by sample 5～10mg, in high-purity N2Under protection, with the speed of 2 DEG C/min, sample temperature is risen to 125 DEG C by 25 DEG C。
The profile of described B crystal form canagliflozin crystal product is such as shown in Fig. 3 microphotograph。Habit microphotograph is observed by polarizing microscope (OLYMPUSBX51, MicroPublisher5.0RTU) and is recorded and obtains。
The preparation method of B crystal form canagliflozin crystal of the present invention is as follows:
Being added in alcohols solvent by canagliflozin crude product, be configured to the suspension of 0.1～0.5g/mL, under stirring action, make solid be completely dissolved at 48～70 DEG C, drip dissolved agent in solution, dissolved agent consumption is 3～10 times of alcohols solvent volume, obtains suspension；Then solvent is evaporated at 48～70 DEG C；The suspension that sucking filtration is obtained, dries and obtains B crystal form canagliflozin crystal product。
The purity 92.0%～96.0% of described canagliflozin crude product。
The described alcohols solvent mixed solvent of one or more in methanol, ethanol, n-butyl alcohol, isobutanol, sec-butyl alcohol, normal propyl alcohol, isopropanol, ethylene glycol, n-amyl alcohol or isoamyl alcohol。
The described dissolved agent mixture of one or more in normal heptane, normal hexane, hexamethylene, normal octane, n-butyl ether, petroleum ether, ether or water。
In described method, the drop rate of dissolved agent is the 0.1%～5% of dropping dissolved agent volume per minute。
In described method, the amount of the solvent evaporated accounts for the 20～80% of liquor capacity。
In described method, evaporation dissolving agent process controls to complete in 5～10 hours。
In described method dry be 20～65 DEG C, normal pressure when carry out 6～10h。
The inventive method has the advantages that operation efficient, easy, consuming time short。The B crystal form canagliflozin Crystal solubility prepared is bigger, rate of dissolution faster, the purity of product higher than 99%, yield about 95%, after product stores 100 days under room temperature, drying condition, product purity, color, form do not change。Product is prone to pulverize and be prone to add the dosage form of pharmaceutical composition, and cost is low, it is easier to commercial industries scale is implemented。
B crystal form canagliflozin provides a new crystal formation as the selection of canagliflozin, and the application of Ka Gelie is provided more choices。
Described B crystal form canagliflozin is applied to the raw material of the effective ingredient of 1 type and type 2 diabetes mellitus, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, post prandial hyperglycemia, hyperinsulinemia。
Accompanying drawing explanation
Fig. 1: the X-ray powder diffraction pattern of B crystal form canagliflozin crystal；
Fig. 2: the dsc analysis figure of B crystal form canagliflozin crystal；
Fig. 3: the microphotograph of B crystal form canagliflozin crystal。
Detailed description of the invention
Embodiment 1:
Canagliflozin 10.02g dry, purity 92.0% is added in 100mL isoamyl alcohol and form suspension, under agitation this suspension is heated to 48 DEG C, make solid all dissolve, with the speed of 0.3mL/min to the normal butane dripping 300mL in solution, obtain suspension；Then, from 48 DEG C, in 5 hours, 80mL solvent is evaporated；Filter suspension and obtain wet crystal product, by its 20 DEG C, under normal pressure dry 10 hours to constant weight, obtain B crystal form canagliflozin product。The X-ray powder diffraction of product as it is shown in figure 1, it is in the angle of diffraction 2 θ=3.42,6.64,12.64,13.27,15.30,15.65,16.59,19.45,19.88,23.79 there is characteristic peak at degree place, dsc analysis figure is as in figure 2 it is shown, have endothermic peak at 84.2 DEG C of places, and its microphotograph is as shown in Figure 3。
The B crystal form canagliflozin product stability prepared is good, purity 99.3%, yield 92.3%, and after product stores 100 days under room temperature, drying condition, product purity, color, form do not change。Product is prone to pulverize and be prone to add the dosage form of pharmaceutical composition。
Embodiment 2:
Canagliflozin 21.98g dry, purity 93.0% is added in 100mL normal propyl alcohol and form suspension, under agitation this suspension is heated to 55 DEG C, solid is made all to dissolve, with the speed of 8.5mL/min to the mixing dissolved agent dripping the normal heptane of 550mL and the hexamethylene of 300mL in solution, obtain suspension, then, from 55 DEG C, in 10 hours, 380mL solvent is evaporated；The suspension being filtrated to get obtains wet crystal product, by its 45 DEG C, under normal pressure dry 7 hours to constant weight, obtain B crystal form canagliflozin product。The X-ray powder diffraction pattern of product is in the angle of diffraction 2 θ=3.41, and there is characteristic peak at 6.69,12.67,13.25,15.30,15.66,16.58,19.46,19.88,23.78 degree of places, and DSC has endothermic peak at 84.8 DEG C of places。
The B crystal form canagliflozin product stability prepared is good, purity 99.1%, yield 93.6%, and after product stores 100 days under room temperature, drying condition, product purity, color, form do not change。Product is prone to pulverize and be prone to add the dosage form of pharmaceutical composition。
Embodiment 3:
Canagliflozin 35.55g dry, purity 95.0% is added 20mL sec-butyl alcohol and 80mL normal propyl alcohol are formed suspension, under agitation this suspension is heated to 60 DEG C, make solid all dissolve, with the speed of 15mL/min to the normal hexane dripping 500mL in solution, obtain suspension；Then, from 60 DEG C, in 8 hours, the solvent of 360mL is evaporated；The suspension being filtrated to get obtains wet crystal product, by its 35 DEG C, under normal pressure dry 6 hours to constant weight, obtain B crystal form canagliflozin product。The X-ray powder diffraction of product is in the angle of diffraction 2 θ=3.40, and there is characteristic peak at 6.69,12.64,13.26,15.30,15.65,16.57,19.43,19.86,23.79 degree of places, and DSC has endothermic peak at 83.9 DEG C of places。
The B crystal form canagliflozin product stability prepared is good, purity 99.2%, yield 94.5%, and after product stores 100 days under room temperature, drying condition, product purity, color, form do not change。Product is prone to pulverize and be prone to add the dosage form of pharmaceutical composition。
Embodiment 4:
Canagliflozin 50.03g dry, purity 96.0% is added 30mL n-butyl alcohol and 70mL ethanol are formed suspension, under agitation this suspension is heated to 70 DEG C, solid is made all to dissolve, in solution, drip the normal heptane of 800mL and the mixing dissolved agent of 200mL water with the speed of 50mL/min, obtain suspension；Then 70 DEG C of beginnings, in 9 hours, the solvent of 880mL is evaporated；The suspension being filtrated to get obtains wet crystal product, by its 65 DEG C, under normal pressure dry 5 hours to constant weight, obtain B crystal form canagliflozin product。The X-ray powder diffraction angle of diffraction 2 θ=3.42 of product, there is characteristic peak at 6.68,12.64,13.26,15.30,15.66,16.58,19.43,19.87,23.78 degree of places, and DSC has endothermic peak at 84.5 DEG C of places。
The B crystal form canagliflozin product stability prepared is good, purity 99.1%, yield 95.2%, and after product stores 100 days under room temperature, drying condition, product purity, color, form do not change。Product is prone to pulverize and be prone to add the dosage form of pharmaceutical composition。
Canagliflozin novel crystal forms of disclosure and proposition and preparation method thereof, those skilled in the art can by link realizations such as reference present disclosure, suitable feed change, technological parameters。The method of the present invention and product have passed through preferred embodiment and are described, method described herein and product substantially can be modified or suitably change and combination by person skilled in without departing from present invention, spirit and scope, 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 art, they are considered as including in present invention spirit, scope and content。
Claims (4)
1. the crystal formation of a canagliflozin, it is characterised in that its X-ray powder diffraction in the angle of diffraction 2 θ=3.4 ± 0.1,6.6 ± 0.1,12.6 ± 0.1,13.2 ± 0.1,15.3 ± 0.1,15.6 ± 0.1,16.5 there is characteristic peak at ± 0.1,19.4 ± 0.1,19.8 ± 0.1 and 23.7 ± 0.1 degree of places；And this crystal formation has DSC endothermic peak at 84 ± 2 DEG C of places。
2. the preparation method of canagliflozin crystal formation as claimed in claim 1, is characterized in that:
Canagliflozin crude product is added in alcohols solvent, it is configured to the suspension of 0.1～0.5g/mL, under stirring action, solid is made to be completely dissolved at 48～70 DEG C, dissolved agent is dripped in solution, dissolved agent consumption is 3～10 times of alcohols solvent volume, and the drop rate of dissolved agent is the 0.1%～5% of dropping dissolved agent volume per minute, obtains suspension；Then evaporating solvent at 48～70 DEG C, the amount of the solvent evaporated accounts for the 20～80% of liquor capacity, and evaporation solvent time is 5～10 hours；The suspension that sucking filtration is obtained, dries and obtains described canagliflozin crystal formation product；
The described alcohols solvent mixed solvent of one or more in methanol, ethanol, n-butyl alcohol, isobutanol, sec-butyl alcohol, normal propyl alcohol, isopropanol, ethylene glycol, glycerol, n-amyl alcohol or isoamyl alcohol；The described dissolved agent mixture of one or more in normal heptane, normal hexane, hexamethylene, normal octane, n-butyl ether, petroleum ether or ether。
3. preparation method as claimed in claim 2, it is characterized in that described drying condition to be temperature be 20～65 DEG C, normal pressure when dry 6～10h。
4. the crystal formation of canagliflozin as claimed in claim 1 is for preparing the purposes in the medicine for the treatment of 1 type and type 2 diabetes mellitus, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, hyperglycemia, hyperinsulinemia。
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015071761A2 (en) * | 2013-11-11 | 2015-05-21 | Crystal Pharmatech Co., Ltd. | Crystalline forms b, c, and d of canagliflozin |
| WO2016016774A1 (en) * | 2014-07-31 | 2016-02-04 | Sun Pharmaceutical Industries Limited | Crystalline forms of canagliflozin |
| 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 |
| CN104530024B (en) * | 2015-02-04 | 2017-08-08 | 上海迪赛诺药业有限公司 | Crystal formation of 1 (β D glycopyranosyls) 4 methyl 3 [5 (4 fluorophenyl) 2 thienyl methyls] benzene and preparation method thereof |
| 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 |
| CN106588898A (en) | 2017-02-20 | 2017-04-26 | 浙江华海药业股份有限公司 | Preparation method for amorphous form of canagliflozin |
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 |
| 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 |
| CN103588762A (en) * | 2013-11-27 | 2014-02-19 | 苏州晶云药物科技有限公司 | Novel crystal form of canagliflozin and its preparation method |
| 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 CN201410129787.1A patent/CN103980262B/en not_active Expired - Fee Related
Patent Citations (11)
| 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 |
| CN103588762A (en) * | 2013-11-27 | 2014-02-19 | 苏州晶云药物科技有限公司 | Novel crystal form of canagliflozin and its preparation method |
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