WO2012115249A1 - Cristal de dérivé de spirocétal - Google Patents

Cristal de dérivé de spirocétal Download PDF

Info

Publication number
WO2012115249A1
WO2012115249A1 PCT/JP2012/054648 JP2012054648W WO2012115249A1 WO 2012115249 A1 WO2012115249 A1 WO 2012115249A1 JP 2012054648 W JP2012054648 W JP 2012054648W WO 2012115249 A1 WO2012115249 A1 WO 2012115249A1
Authority
WO
WIPO (PCT)
Prior art keywords
type
crystal
stirring
crystals
producing
Prior art date
Application number
PCT/JP2012/054648
Other languages
English (en)
Japanese (ja)
Inventor
政利 村形
正弘 永瀬
伸彰 木村
友之 島村
覚 有本
直 武田
効彦 中野
則幸 高田
隆充 植戸
智嗣 谷田
Original Assignee
中外製薬株式会社
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 中外製薬株式会社 filed Critical 中外製薬株式会社
Priority to JP2013501153A priority Critical patent/JP6294665B2/ja
Publication of WO2012115249A1 publication Critical patent/WO2012115249A1/fr

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/01—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing oxygen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • the present invention relates to a novel crystalline form of 1,1-anhydro-1-C- [5- (4-ethylphenyl) methyl-2- (hydroxylmethyl) phenyl] - ⁇ -D-glucopyranose, a spiroketal derivative. .
  • Patent Document 1 WO2006 / 080421 (Patent Document 1) describes the formula (I):
  • a compound represented by: 1,1-anhydro-1-C- [5- (4-ethylphenyl) methyl-2- (hydroxylmethyl) phenyl] - ⁇ -D-glucopyranose is disclosed. It has been described as having excellent SGLT2 inhibitory activity.
  • Patent Document 2 discloses a monohydrate crystal, a sodium acetate cocrystal and a potassium acetate cocrystal of the compound represented by the formula (I), and this monohydrate crystal ( (Hereinafter referred to as “type I crystal”) in the powder X-ray diffraction pattern, 3.5 °, 6.9 °, 10.4 °, 13.8 °, 16.0 °, 17.2 °, 18.4 It is described that it has a peak at diffraction angles (2 ⁇ ) in the vicinity of °, 20.8 °, 21.4 °, and 24.4 °.
  • sodium acetate co-crystal is 4.9 °, 8.7 °, 9.3 °, 11.9 °, 12.9 °, 14.7 °, 16. It has peaks at diffraction angles (2 ⁇ ) around 0 °, 17.1 °, 17.7 °, 19.6 °, 21.6 °, and 22.0 °, and the potassium acetate co-crystal has powder X-rays In the diffraction pattern, 5.0 °, 10.0 °, 10.4 °, 12.4 °, 14.5 °, 15.1 °, 19.0 °, 20.1 °, 21.4 °, and It is described that it has a peak at a diffraction angle (2 ⁇ ) near 25.2 °.
  • the compound represented by the formula (I) has an excellent effect as a pharmaceutical product.
  • Certain monohydrate crystals of the compound (type I crystals) and co-crystals with acetate are known, but no other crystal forms have been reported.
  • the object of the present invention is to use 1,1-anhydro-1-C- [5- (4-ethylphenyl) methyl-2- (hydroxylmethyl) phenyl] - ⁇ -D-glucopyranose used as an active ingredient of pharmaceuticals It is to provide a novel crystal form of
  • the present inventors surprisingly found that the crystalline form of the compound of formula (I) was stirred by stirring it at a specific temperature in the presence of moisture. And found that a new crystal form was obtained.
  • the present inventors have also found that the novel crystalline form can be obtained by stirring an amorphous compound of formula (I) at a specific temperature in the presence of moisture.
  • Said type II crystals having (3) A crystal of the compound represented by the above formula (I), and in a powder X-ray diffraction pattern, 4.0 °, 12.7 °, 14.7 °, 18.0 °, 19.5 ° , And the type II crystal having a peak at a diffraction angle (2 ⁇ ) near 22.7 °.
  • a pharmaceutical composition comprising the type II crystal described in any of (1) to (7) above.
  • diabetes diabetic complications resulting from hyperglycemia, or obesity
  • administering the crystal according to any one of (1) to (7) to a subject comprising administering the crystal according to any one of (1) to (7) to a subject.
  • a method of preventing or treating the disease is provided.
  • the production methods (8) to (13) are provided.
  • a method for producing a type II crystal according to 1. (9) The method for producing a type II crystal according to the above (8), comprising a step of stirring the wet type I crystal having a water content of 13 to 43% by weight. (10) In the step of stirring the wet type I crystal having a water content of 13 to 43% by weight, the wet type I crystal is stirred under reduced pressure to perform transition to the type II crystal and removal of water.
  • the manufacturing methods of (14) and (15) are provided.
  • (14) The method for producing a type II crystal according to any one of the above (1) to (7), comprising stirring an amorphous compound of the formula (I) at a temperature of 0 to 30 ° C.
  • (15) The method according to any one of (1) to (7) above, comprising stirring an amorphous compound of the formula (I) containing 8% by weight or less of water at a temperature of 0 to 30 ° C.
  • the crystal of the compound of the formula (I) provided by the present invention exists stably at room temperature and has characteristics suitable as a pharmaceutical raw material. Moreover, since handling at the time of formulation is easy, it is excellent as a raw material for safely and stably producing a pharmaceutical comprising the compound of formula (I) as an active ingredient.
  • the pharmaceutical composition containing the crystal is excellent in storage stability.
  • FIG. 1 An example of the results of differential scanning calorimetry of type II crystals of 1,1-anhydro-1-C- [5- (4-ethylphenyl) methyl-2- (hydroxylmethyl) phenyl] - ⁇ -D-glucopyranose
  • FIG. 1 An example of the results of differential scanning calorimetry of type II crystals of 1,1-anhydro-1-C- [5- (4-ethylphenyl) methyl-2- (hydroxylmethyl) phenyl] - ⁇ -D-glucopyranose
  • FIG. 5 is an enlarged view of a portion at a temperature of 100 ° C. to 100 ° C.
  • Example of measurement result of powder X-ray diffraction of type III crystal of 1,1-anhydro-1-C- [5- (4-ethylphenyl) methyl-2- (hydroxylmethyl) phenyl] - ⁇ -D-glucopyranose FIG. 5
  • the crystal of the compound of formula (I) according to the present invention (type II crystal) is characterized by having a peak in the vicinity of a specific diffraction angle (2 ⁇ ) in the powder X-ray diffraction pattern.
  • analysis by powder X-ray diffraction can be performed according to a conventional method such as “powder X-ray diffraction measurement method” described in Japanese Pharmacopoeia (15th revision), for example. According to the Japanese Pharmacopoeia, it is generally explained that the diffraction angle 2 ⁇ coincides within a range of ⁇ 0.2 degrees in the same crystal form.
  • Measuring device X'Pert-Pro MPD (manufactured by Panallytical), Counter cathode: Cu, Tube voltage: 45 kV, Tube current: 40 mA, Step width: 0.017, Scanning axis: 2 ⁇ Sampling time per step: 30 seconds, Scanning range: 2 to 35 °.
  • the type II crystal of the present invention is characterized in that when a temperature rise is measured using an airtight cell in differential scanning calorimetry analysis, an endothermic peak, an exothermic peak, and an endothermic peak are detected in this order at 50 to 80 ° C.
  • the differential scanning calorimeter analysis can be performed, for example, according to the “heat flux differential scanning calorimetry” described in the Japanese Pharmacopoeia (15th revision).
  • An airtight cell is preferably used as the sample container.
  • the airtight cell those described in the following documents can be used: "Basics and Applications of New Thermal Analysis", edited by the Japan Society for Thermometry, published by Realize Science and Technology Center (July 1989), p. 40; and "Basics of Thermal Analysis for Material Chemistry", written by Yasutoshi Saito, Kyoritsu Shuppan (December 1990), pages 63-65.
  • DSC Differential scanning calorimeter
  • Q200 manufactured by TA Instruments
  • Heating rate 2 ° C / min
  • Measurement temperature range about 25 ° C to 250 ° C
  • Atmospheric gas dry nitrogen
  • Atmospheric gas flow rate 50 mL / min
  • Cell Aluminum pan (airtight)
  • Sample amount about 5 mg
  • Standard Empty container.
  • the endothermic peak and the exothermic peak of the same crystal form are usually matched within a range of ⁇ 1.3 ° C.
  • NIR analysis is performed on specimens such as type I crystals, type II crystals, and amorphous, and PLS regression analysis of multivariate analysis is performed on the measurement results to create a calibration curve. The abundance ratio of crystal and amorphous can be calculated.
  • the type II crystal of the present invention is a monohydrate.
  • the water content of the type II crystal can be measured by a conventional method, for example, by the Karl Fischer method.
  • An example of the measurement conditions of the moisture measurement method using a Karl Fischer analyzer is shown below: Analytical method: coulometric titration method, KF analyzer: Trace moisture analyzer Model KF-100 (Mitsubishi Chemical Corporation), Anolyte: Aquamicron AX (Mitsubishi Chemical) Catholyte: Aquamicron CXU (Mitsubishi Chemical).
  • the type II crystal of the present invention is obtained by converting a monohydrate crystal (type I crystal) of the compound of the above formula (I) to a temperature lower than room temperature, for example, 0 to 15 ° C., preferably 0 to 10 in the presence of moisture. It can be prepared by stirring at a temperature of ° C.
  • a type II crystal it is preferable to use a type I crystal having a water content of 13% by weight or more as a raw material.
  • a wet type I crystal particularly a wet powder of type I crystal
  • An aqueous suspension suspended in water can be used as a raw material.
  • the water required for the generation of the type II crystal may be, for example, crystal water contained in the raw material type I crystal and water adhering to the crystal.
  • the amount of water contained in the wet type I crystal, including crystal water is, for example, 13% by weight or more, preferably 13 to 43% by weight, more preferably 20 to 43% by weight.
  • the transition from wet type I crystal to type II crystal is initiated by impact, compression, crushing, mixing, kneading and the like.
  • the transition to the type II crystal is achieved, for example, by stirring the wet type I crystal.
  • the stirring means include a stirring bar, a magnetic stirrer and a magnetic stirrer, a mechanical stirrer with a stirring blade, a paddle stirrer, and a stirring filter dryer.
  • the stirring time for transferring the I-type crystal to the II-type crystal can be appropriately adjusted depending on fluctuations in conditions such as stirring efficiency, and is, for example, 1 hour or longer, preferably 6 hours or longer.
  • the transition in order to perform transition from type I crystal to type II crystal and removal of excess water, the transition can be advanced by stirring under reduced pressure.
  • the pressure under the reduced pressure condition is, for example, pressure: 0 to 30 hPa, preferably 20 to 30 hPa.
  • the transition from the I-type crystal to the II-type crystal can be advanced by stirring under reduced pressure drying conditions. Stirring under dry conditions can be performed using, for example, a filter dryer.
  • the I-type crystal it is also possible to transfer the I-type crystal to the II-type crystal by stirring the aqueous suspension of the I-type crystal.
  • a suspension of a mixture of a type I crystal and a type II crystal in water is stirred.
  • a type I crystal can be transferred to a type II crystal by a method in which a seed crystal of a type II crystal is added to an aqueous suspension of the type crystal.
  • the stirring means include a stirring bar, a magnetic stirrer and a magnetic stirrer, a mechanical stirrer with a stirring blade, a paddle stirrer, and a stirring filter dryer.
  • a mixture of type I crystals and type II crystals obtained by directly stirring wet type I crystal powder is suspended in water, and the aqueous suspension is further stirred. A mold crystal is produced.
  • the type II crystal of the present invention can be prepared by stirring an amorphous compound of the above formula (I) in the presence of moisture at a temperature of, for example, 0 to 30 ° C., preferably 10 to 25 ° C.
  • a type II crystal an amorphous material containing 8% by weight or less, for example, 0.001% by weight or more and 8% by weight or less can be used as a raw material, and the moisture content is 4.6% by weight.
  • an amorphous material of 0.001% by weight or more and 4.6% by weight or less is preferable.
  • the transition from amorphous to type II crystal is initiated by impact, compression, crushing, mixing, kneading and the like. Specifically, the transition to the type II crystal is achieved, for example, by stirring the amorphous.
  • the stirring means include a stirring bar, a magnetic stirrer and a magnetic stirrer, a mechanical stirrer with a stirring blade, a paddle stirrer, and a stirring filter dryer.
  • the stirring time for transferring the amorphous to the II-type crystal can be appropriately adjusted depending on fluctuations in conditions such as stirring efficiency, but is, for example, 1 hour or longer, preferably 6 hours or longer.
  • the transition in order to transition from amorphous to type II crystal, the transition can be advanced by stirring under reduced pressure.
  • the pressure under the reduced pressure condition is, for example, pressure: 0 to 30 hPa, preferably 20 to 30 hPa.
  • the purity of the type II crystal contained in the crystal obtained by the production method of the present invention is, for example, 1% by weight or more, preferably 50% by weight or more, more preferably 90% by weight or more.
  • Type III crystals can be obtained, for example, by precipitating the compound of formula (I) from a mixture of acetone and water, and in the powder X-ray diffraction pattern, at a diffraction angle (2 ⁇ ) near 19.2 °, Specifically, diffraction angles (2 ⁇ ) around 11.0 °, 19.2 °, and 21.6 °, more specifically 11.0 °, 12.3 °, 19.2 °, 20.2 It has a peak at a diffraction angle (2 ⁇ ) in the vicinity of ° and 21.6 °.
  • FIG. 4 An example of the measurement result of the powder X-ray diffraction of the type III crystal is shown in FIG. 4, and an example of the peak in the powder X-ray diffraction pattern is shown below. Further, from the examination using TG-DTA-MS, the type III crystal was determined to be a solvate of water and acetone.
  • the type I crystal can also be obtained by stirring a suspension of water added to the type III crystal obtained by filtration.
  • the temperature at the time of stirring is set to 0 to 30 ° C., preferably 10 to 30 ° C., more preferably 20 to 30 ° C.
  • stirring time can be suitably adjusted with the fluctuation
  • a pharmaceutical composition comprising type II crystals of the compound of formula (I) above.
  • the compound of the said formula (I) has the inhibitory activity of the sodium dependence glucose cotransporter 2 (SGLT2) in connection with glucose reabsorption in a kidney (patent document 1 etc.).
  • SGLT2 sodium dependence glucose cotransporter 2
  • the pharmaceutical composition of the present invention can be used to prevent or treat diseases or conditions that can be ameliorated by inhibiting the activity of SGLT2, such as diabetes, diabetes-related diseases and diabetic complications.
  • Diabetes includes type 1 diabetes, type 2 diabetes, and other types of diabetes due to specific causes.
  • Diabetes-related diseases include, for example, obesity, hyperinsulinemia, glucose metabolism disorder, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, lipid metabolism disorder, hypertension, congestive heart failure, edema, high This includes uricemia and gout.
  • Diabetic complications includes both acute complications and chronic complications. Examples of “acute complications” include hyperglycemia (ketoacidosis, etc.), infections (skin, soft tissue, biliary system, respiratory system, urinary tract infection, etc.), etc.
  • Angiopathy nephropathy, retinopathy
  • arteriosclerosis arteriosclerosis
  • myocardial infarction cerebral infarction
  • cerebral infarction cerebral infarction
  • lower limb arterial occlusion etc.
  • neuropathy sensor nerve, motor nerve, autonomic nerve, etc.
  • foot gangrene etc.
  • Major diabetic complications include diabetic retinopathy, diabetic nephropathy, diabetic neuropathy.
  • the pharmaceutical composition of the present invention contains, as an additional active ingredient, a therapeutic agent for diabetes, a therapeutic agent for diabetic complications, a therapeutic agent for hyperlipidemia, a therapeutic agent for hypertension and the like having a different mechanism of action other than the SGLT2 inhibitor. Or may be used in combination with these agents.
  • the pharmaceutical composition of the present invention can be systemically or locally administered orally or parenterally such as rectal, subcutaneous, intramuscular, intravenous, transdermal, etc., and contains a pharmaceutically acceptable carrier.
  • excipients and extenders examples include lactose, magnesium stearate, starch, talc, gelatin, agar, pectin, gum arabic, and other commonly used ones.
  • the dose of the compound of the above formula (I) varies depending on the disease, symptoms, body weight, age, sex, route of administration, etc. 1 to 1000 mg / kg body weight / day, more preferably 0.1 to 200 mg / kg body weight / day, which can be administered once or divided into several times a day.
  • Acetone (620 kg) and water (16 kg) were added to the obtained crude product, and the solvent was distilled off under reduced pressure.
  • Acetone (186 kg) and water (16 kg) were added to the obtained residue, and the temperature was raised to 54 ° C. to dissolve the crude product.
  • acetone (13.1 kg) and water (298 kg) were added, and the solution was heated to 40 ° C. and filtered. The residue was washed with water (940 kg) and the washing solution was added to the filtrate.
  • the obtained wet powder was dried under reduced pressure for 57 hours using a filter dryer (rotation speed: 4 rpm, pressure: 25 hPa) to give 1-anhydro-1-C- [5- (4-ethylphenyl) methyl-2 -(Hydroxylmethyl) phenyl] - ⁇ -D-glucopyranose (68.8 kg, water content: 4.68%) was obtained as a mixture of type I and type II crystals. Subsequently, the mixture (68.6 kg) was pulverized to obtain a pulverized powder (66.4 kg).
  • the seed crystal used twice in Example 1 is 1,1-anhydro-1-C- [5- (4-ethylphenyl) methyl-2-obtained according to Step 5 of Example 5 of WO2009 / 154276.
  • a portion of the monohydrate crystal (type I crystal) of (hydroxylmethyl) phenyl] - ⁇ -D-glucopyranose was used.
  • the moisture content was measured by the following method.
  • Analytical method coulometric titration method
  • KF analyzer Trace moisture analyzer Model KF-100 (Mitsubishi Chemical)
  • Anolyte Aquamicron AX (Mitsubishi Chemical)
  • Catholyte Aquamicron CXU (Mitsubishi Chemical).
  • Example 1 the following filter dryer was used: Manufacturer: Rosenmund, Total capacity: 3530L, Diameter: 1800mm, Filtration area: 2.5 m 2 Stirring blade: 2-blade.
  • a part (5 g, moisture content: 47%) of the obtained wet powder was put in a test tube (inner diameter 35 mm), and a polytetrafluoroethylene stirrer (rugby ball type, The mixture was stirred for 22 hours using a total length of 25 mm (150 rpm, Personal Organic Synthesizer PPS-CTRL1 manufactured by EYELA). Subsequently, the mixture was stirred (150 rpm) for 24 hours at 10 ° C. (external temperature) under reduced pressure (pressure: 25 hPa) to obtain the title compound (wet powder, water content: 36%). Powder X-ray diffraction of the obtained crystal was measured, and it was confirmed that the crystal was a mixture of type I crystal and type II crystal.
  • the seed crystal used in Example 2 is 1,1-anhydro-1-C- [5- (4-ethylphenyl) methyl-2- (hydroxyl) obtained according to Step 5 of Example 5 of WO2009 / 154276.
  • a portion of the monohydrate crystal (type I crystal) of methyl) phenyl] - ⁇ -D-glucopyranose was used.
  • a type II crystal can be obtained by performing the same operation as in Example 1 on the mixture of the type I crystal and the type II crystal obtained in Example 2.
  • Example 3 Preparation of type II crystals of 1,1-anhydro-1-C- [5- (4-ethylphenyl) methyl-2- (hydroxylmethyl) phenyl] - ⁇ -D-glucopyranose 1,1, -Anhydro-1-C- [5- (4-ethylphenyl) methyl-2- (hydroxylmethyl) phenyl] - ⁇ -D-glucopyranose type I crystals (2.3 g) were prepared on a hot plate (manufactured by IKA) C-MAGHP4) was heated and melted at 95 ° C. for 1.5 hours, and then cooled to room temperature to prepare an amorphous. The prepared amorphous was ground with a mortar.
  • amorphous water content of Examples 3 and 4 and the water content of the sample after NIR measurement of Example 3 were measured by the Karl Fischer method. The measurement conditions are shown below.
  • Analytical method coulometric titration method
  • KF analyzer Trace moisture analyzer Model CA-100 (Mitsubishi Chemical Corporation)
  • Anolyte Aquamicron AKX
  • Catholyte Aquamicron CXU.
  • NIR measurement method The sample lightly ground in a mortar was taken in a sample bottle and stored in a desiccator of 10% RH or less for 2 to 6 hours. Thereafter, the abundance ratio of the type II crystal and the amorphous was measured using a NIR measuring device (manufactured by BRUKER, MPA). The sample was measured after measuring the background once under the following measurement conditions. The measurement was repeated 5 times, and the sample inside was lightly stirred while tilting and rotating the sample bottle every time. However, since the grain size may be biased, tapping to hit the desk was not performed.
  • the type II crystal of the present invention is obtained by stirring the type I crystal or amorphous in the presence of a specific amount of water at a specific temperature.
  • DSC Differential scanning calorimetry
  • DSC differential scanning calorimeter
  • Model Q200 (manufactured by TA Instruments)
  • Heating rate 2 ° C / min
  • Measurement temperature range Temperature around 25 °C ⁇ 250 °C
  • Atmospheric gas Dry nitrogen Atmospheric gas flow rate: 50 mL / min
  • Cell Aluminum pan (airtight) Sample amount: about 5mg Standard: Empty container.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Diabetes (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Emergency Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)

Abstract

La présente invention concerne une nouvelle forme cristalline de 1,1-anhydro-1-C-[5-(4-éthylphényl)méthyl-2-(hydroxyl- méthyl)phényl]-β-D-glucopyranose, qui présente un pic à un angle de diffraction angle (2θ) d'environ 4,0˚ dans un diffractogramme de poudre par rayons X.
PCT/JP2012/054648 2011-02-25 2012-02-24 Cristal de dérivé de spirocétal WO2012115249A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2013501153A JP6294665B2 (ja) 2011-02-25 2012-02-24 スピロケタール誘導体の結晶

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2011040418 2011-02-25
JP2011-040418 2011-02-25

Publications (1)

Publication Number Publication Date
WO2012115249A1 true WO2012115249A1 (fr) 2012-08-30

Family

ID=46721021

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2012/054648 WO2012115249A1 (fr) 2011-02-25 2012-02-24 Cristal de dérivé de spirocétal

Country Status (2)

Country Link
JP (1) JP6294665B2 (fr)
WO (1) WO2012115249A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015099139A1 (fr) 2013-12-27 2015-07-02 中外製薬株式会社 Préparation solide comprenant de la tofogliflozine et procédé de production associé
CN107759649A (zh) * 2017-12-12 2018-03-06 威海贯标信息科技有限公司 一种托格列净新晶型
CN108640958A (zh) * 2017-05-05 2018-10-12 镇江圣安医药有限公司 异苯并呋喃衍生物、其药物组合物和制剂以及用途

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006080421A1 (fr) * 2005-01-28 2006-08-03 Chugai Seiyaku Kabushiki Kaisha Dérivé de spirocétal et emploi dudit dérivé au titre de médicament contre le diabète
WO2009154276A1 (fr) * 2008-06-20 2009-12-23 中外製薬株式会社 Cristaux de dérivé de spirocétal et leur procédé de fabrication

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006080421A1 (fr) * 2005-01-28 2006-08-03 Chugai Seiyaku Kabushiki Kaisha Dérivé de spirocétal et emploi dudit dérivé au titre de médicament contre le diabète
WO2009154276A1 (fr) * 2008-06-20 2009-12-23 中外製薬株式会社 Cristaux de dérivé de spirocétal et leur procédé de fabrication

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
CHEUNG EUGENE Y. ET AL.: "Reconciling thermal and structural data from the polymorphic transitions of malonamide", THERMOCHIMICA ACTA, vol. 482, 2009, pages 57 - 61 *
LI HUI ET AL.: "Investigations on Solid-Solid Phase Transformation of 5-Methyl-2-[(4-Methyl- 2-Nitrophenyl)Amino]-3-Thiophenecarbonitrile", JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 96, no. 5, 2007, pages 1079 - 1089 *
NORIAKI HIRAYAMA, YUKI KAGOBUTSU KESSHO SAKUSEI HANDBOOK -GENRI TO KNOW-HOW, 25 July 2008 (2008-07-25), pages 68 - 73, 82-83 *
OTSUKA MAKOTO ET AL.: "RELATION BETWEEN POLYMORPHIC TRANSFORMATION PATHWAY DURING GRINDING AND THE PHYSICOCHEMICAL PROPERTIES OF BULK POWDERS FOR PHARMACEUTICAL PREPARATIONS", DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, vol. 20, no. 9, 1994, pages 1649 - 1660 *
YADA SHUICHI ET AL.: "Solid phase transition of CS-891 enantiotropes during grinding", INTERNATIONAL JOURNAL OF PHARMACEUTICS, vol. 255, 2003, pages 69 - 79 *

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2020203918A (ja) * 2013-12-27 2020-12-24 中外製薬株式会社 トホグリフロジンを含有する固形製剤及びその製造方法
KR102395687B1 (ko) * 2013-12-27 2022-05-06 추가이 세이야쿠 가부시키가이샤 토포글리플로진을 함유하는 고형 제제 및 그 제조 방법
JPWO2015099139A1 (ja) * 2013-12-27 2017-03-23 中外製薬株式会社 トホグリフロジンを含有する固形製剤及びその製造方法
TWI774159B (zh) * 2013-12-27 2022-08-11 日商中外製藥股份有限公司 含有托格列淨（Tofogliflozin）之固體製劑及其製造方法
JP2019112424A (ja) * 2013-12-27 2019-07-11 中外製薬株式会社 トホグリフロジンを含有する固形製剤及びその製造方法
US10231930B2 (en) 2013-12-27 2019-03-19 Chugai Seiyaku Kabushiki Kaisha Solid preparations containing tofogliflozin and process of producing the same
KR20160101719A (ko) 2013-12-27 2016-08-25 추가이 세이야쿠 가부시키가이샤 토포글리플로진을 함유하는 고형 제제 및 그 제조 방법
US10398653B2 (en) 2013-12-27 2019-09-03 Chugai Seiyaku Kabushiki Kaisha Solid preparations containing tofogliflozin and process of producing the same
EP3482748A1 (fr) 2013-12-27 2019-05-15 Chugai Seiyaku Kabushiki Kaisha Préparations solides comprenant de la tofogliflozine et procédé de production associé
WO2015099139A1 (fr) 2013-12-27 2015-07-02 中外製薬株式会社 Préparation solide comprenant de la tofogliflozine et procédé de production associé
JP2022116267A (ja) * 2013-12-27 2022-08-09 中外製薬株式会社 トホグリフロジンを含有する固形製剤及びその製造方法
KR20210082557A (ko) 2013-12-27 2021-07-05 추가이 세이야쿠 가부시키가이샤 토포글리플로진을 함유하는 고형 제제 및 그 제조 방법
CN108640958A (zh) * 2017-05-05 2018-10-12 镇江圣安医药有限公司 异苯并呋喃衍生物、其药物组合物和制剂以及用途
CN108640958B (zh) * 2017-05-05 2021-03-30 镇江圣安医药有限公司 异苯并呋喃衍生物、其药物组合物和制剂以及用途
CN107759649A (zh) * 2017-12-12 2018-03-06 威海贯标信息科技有限公司 一种托格列净新晶型

Also Published As

Publication number Publication date
JP6294665B2 (ja) 2018-03-14
JPWO2012115249A1 (ja) 2014-07-07

Similar Documents

Publication Publication Date Title
JP5091853B2 (ja) １−クロロ−４−（β−Ｄ−グルコピラノス−１−イル）−２−［４−（（Ｒ）−テトラヒドロフラン−３−イルオキシ）ベンジル］ベンゼンの結晶形、その調製方法及び薬剤を調製するための使用
JP4226070B2 (ja) １−クロロ−４−（β−Ｄ−グルコピラノース−１−イル）−２−［４−（（Ｓ）−テトラヒドロフラン−３−イルオキシ）−ベンジル］−ベンゼンの結晶性形態、その調製方法及び薬物を調製するためのその使用
JP5748954B2 (ja) チアゾリジンジオン化合物の結晶およびその製造方法
EP1908757A1 (fr) Cristal de sel de choline de compose azulene
EP3502105A1 (fr) Forme polymorphe d'un composé inhibiteur de kinase, composition pharmaceutique le contenant, son procédé de préparation et son utilisation
AU2011312185B2 (en) New crystalline forms of the sodium salt of (4- {4- [5- ( 6 - trifluoromethyl - pyridin- 3 - ylamino ) - pyridin- 2 -yl] -phenyl} - cyclohexyl) -acetic acid
JP6294665B2 (ja) スピロケタール誘導体の結晶
JP2023062091A (ja) Ｓ１ｐ１受容体アゴニストの付加塩およびその結晶形態、ならびに薬学的組成物
JP2009235088A (ja) ５−ヒドロキシ−１−メチルヒダントイン結晶の製造方法
WO2021196949A1 (fr) Forme cristalline a d'antagoniste du récepteur glp-1 et son procédé de préparation
TWI662031B (zh) １－｛２－氟－４－［５－（４－異丁基苯基）－１，２，４－噁二唑－３－基］－苄基｝－３－吖丁啶羧酸的晶型
JP7322151B2 (ja) 医薬化合物、その製造方法、及び薬剤としての使用
CN113045554A (zh) 一种非索替尼晶型及其制备方法
CN106478616B (zh) 一种gpr40激动剂的结晶形式及其制备方法
WO2022143897A1 (fr) SUBSTANCE POLYMORPHE D'UN COMPOSÉ A-DÉCARBURATION-5α ANDROSTANE
WO2016136830A1 (fr) Nouveau cristal de 1-(b-d-glucopyranosyl)-4-méthyle-3-[5-(4-fluorophényl)-2-thiénylméthyle]benzène
CN113336733B (zh) 一种sglt-2抑制剂的l-脯氨酸共结晶体的制备方法
EP3434677B1 (fr) Polymorphes du maléate inhibiteur de dppiv et leur procédés de préparation
US20230372375A1 (en) Sglt-2 inhibitor sarcosine co-crystal, preparation method therefor and use thereof
KR102672632B1 (ko) S1p1 수용체 작용제의 부가 염 및 이의 결정 형태 및 약제학적 조성물
CN117105923A (zh) 具有高生物利用度的鲁拉西酮盐及其制法和应用
KR20200003645A (ko) 신규한 결정형 및 그의 제조방법
JPH0745404B2 (ja) 骨粗鬆症治療剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12750270

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2013501153

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 12750270

Country of ref document: EP

Kind code of ref document: A1