[go: up one dir, main page]

WO2017047970A1 - Forme cristalline de linagliptine et procédé de préparation de cette dernière - Google Patents

Forme cristalline de linagliptine et procédé de préparation de cette dernière Download PDF

Info

Publication number
WO2017047970A1
WO2017047970A1 PCT/KR2016/010001 KR2016010001W WO2017047970A1 WO 2017047970 A1 WO2017047970 A1 WO 2017047970A1 KR 2016010001 W KR2016010001 W KR 2016010001W WO 2017047970 A1 WO2017047970 A1 WO 2017047970A1
Authority
WO
WIPO (PCT)
Prior art keywords
linagliptin
formula
crystal form
hydroxybenzoic acid
acid salt
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/KR2016/010001
Other languages
English (en)
Korean (ko)
Inventor
문지연
김유림
주준호
이재헌
장영길
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hanmi Fine Chemicals Co Ltd
Original Assignee
Hanmi Fine Chemicals Co Ltd
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 Hanmi Fine Chemicals Co Ltd filed Critical Hanmi Fine Chemicals Co Ltd
Priority to JP2018513310A priority Critical patent/JP2018527363A/ja
Priority to CN201680054246.4A priority patent/CN108290891A/zh
Publication of WO2017047970A1 publication Critical patent/WO2017047970A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
    • C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms

Definitions

  • the present invention relates to a novel linagliptin crystal form and a preparation method thereof, and a pharmaceutical composition for treating diabetes comprising the same as an active ingredient.
  • Linagliptin (8-[(3R) -3-aminopiperidin-1-yl] -7- (but-2-yn-1-yl) -3-methyl-1-[(4-methylquinazolin -2-yl) methyl] -3,7-dihydro-1H-purine-2,6-dione) is usefully used as a raw material for the treatment of diabetes.
  • Linagliptin was approved by the US Food and Drug Administration in 2011 for the treatment of type 2 diabetes and is currently sold under the trade name Tratraenta TM worldwide.
  • Type 1 diabetes in which beta cells are destroyed and no insulin is secreted
  • type 2 diabetes in which insulin action is reduced due to insulin resistance and sufficient secretion is not achieved.
  • Drug therapy uses insulin or hypoglycemic agents.
  • DPP-4 inhibitor dipeptidyl peptidase-4 inhibitor among the hypoglycemic agents used for type 2 diabetes has been attracting much attention, and the blood concentration of GLP-1, which is one of the pathogenesis factors of diabetes, has been increased. It acts to promote insulin secretion.
  • Linagliptin is a recently-developed DPP-4 inhibitor, which is a single dose for patients with impaired renal or hepatic function, since the primary excretory pathway of conventional DPP-4 inhibitors is the kidneys, while most are excreted through the bile and gastrointestinal tract. There is an advantage that can be administered.
  • an object of the present invention is to provide a novel linagliptin crystal form and a method for producing the same, which are excellent in thermal stability, can be reproducibly produced in a single crystal form, and can be mass-produced.
  • Another object of the present invention is to provide a linagliptin 4-hydroxybenzoic acid salt used in the method for preparing the linagliptin crystal form and a method for producing the same.
  • Another object of the present invention to provide a pharmaceutical composition for treating diabetes comprising the linagliptin crystal form as an active ingredient.
  • the present invention is Linagliptin represented by the following formula (1) in the X-ray diffraction spectrum (XRD) 5.6, 9.8, 11.2, 11.8, 13.1, 14.4, 14.9, 16.1, 16.4, 18.4, 18.8, 19.9 Linagliptin crystal form comprising peaks at diffraction angles (2 ⁇ ⁇ 0.2 °) of 20.2, 20.7, 22.0.
  • the present invention comprises the steps of: (1) adding a linagliptin 4-hydroxybenzoic acid salt represented by the following formula (2) in water or an organic solvent, adding a base and then stirring; And (2) filtering the reactants of step (1), and washing the filtered crystals with water and an organic solvent and drying the linagliptin crystal form.
  • the present invention provides a linagliptin 4-hydroxybenzoic acid salt represented by the following general formula (2), which is an intermediate used in the preparation of linagliptin crystal form.
  • the present invention comprises the steps of (i) reacting linagliptin represented by the formula (1) and 4-hydroxybenzoic acid represented by the formula (3) in a solvent; And (ii) obtaining crystals from the solution obtained in the step (i), a process for preparing linagliptin 4-hydroxybenzoic acid salt.
  • the present invention provides a pharmaceutical composition for treating diabetes comprising the linagliptin crystal form as an active ingredient.
  • novel linagliptin crystalline form according to the present invention is not only excellent in thermal stability and can be reproducibly produced in a single crystalline form, and thus can be used as a pharmaceutical composition for treating diabetes because it can be mass produced in a certain quality.
  • Example 1 is a graph showing the results of the X-ray diffraction spectroscopy of the linagliptin crystal form prepared in Example 2.
  • FIG. 2 is a graph showing the results of differential scanning calorimetry (DSC) of linagliptin crystalline form prepared in Example 2.
  • DSC differential scanning calorimetry
  • linagliptin represented by the following Chemical Formula 1 is 5.6, 9.8, 11.2, 11.8, 13.1, 14.4, 14.9, 16.1, 16.4, 18.4, 18.8, 19.9, 20.2 in the X-ray diffraction spectrum (XRD) Linagliptin crystal form comprising peaks at diffraction angles (2 ⁇ ⁇ 0.2 °) of 20.7, 22.0:
  • the linagliptin crystal form is characterized by characteristic 2 ⁇ (2 theta) diffraction angle peaks shown in the X-ray powder diffraction spectrometer irradiated with Cu-K ⁇ light source.
  • linagliptin crystal form according to the present invention is 5.6, 9.8, 11.2, 11.8, 13.1, 14.4, 14.9, 16.1, 16.4, 18.4, 18.8, 19.9, 20.2, 20.7, 22.0, in X-ray powder diffraction analysis
  • Characteristic peaks are shown at diffraction angles (2 ⁇ ⁇ 0.2 °) of 23.6, 24.3, 25.1, 26.4, 27.2, 29.9, 30.9, 31.8, 33.2 and 34.3 (see FIG. 1).
  • the linagliptin crystal form is characterized by showing two endothermic peaks at about 173 ° C. and 206 ° C. in differential scanning calorimetry (DSC) (see FIG. 2).
  • the present invention also provides a method for producing the linagliptin crystal form.
  • the linagliptin crystal form may be prepared by reacting linagliptin 4-hydroxybenzoic acid salt represented by the following formula (2) in the presence of a base in water or an organic solvent, as shown in Scheme 1 below.
  • the method for preparing linagliptin crystal form includes the steps of: (1) adding the linagliptin 4-hydroxybenzoic acid salt to water or an organic solvent, further adding a base, followed by stirring; And (2) filtering the reactants of step (1), and washing and drying the filtered crystals with water and an organic solvent.
  • the solvent is alcohol such as methyl alcohol, ethyl alcohol; Acetone; Water etc. can be used and it is preferable to use water independently. Water can dissolve a variety of bases, avoid the use of various types of organic solvents that were often used in the preparation of known crystalline forms, and remove excess acid that has been separated.
  • the solvent may be used in an amount of 5 to 20 vol, preferably 8 to 15 vol, based on the volume of linagliptin 4-hydroxybenzoic acid salt.
  • the base may be reacted with linagliptin 4-hydroxybenzoic acid salt to form linagliptin crystal form, and organic or inorganic base may be used, and specifically, sodium hydroxide, potassium hydroxide, sodium hydrogencarbonate, Potassium hydrogen carbonate, sodium carbonate, potassium carbonate and the like can be used.
  • the base may be used in an amount of 1 to 10 equivalents, preferably 5 to 10 equivalents based on 1 equivalent of linagliptin 4-hydroxybenzoic acid salt.
  • the solution to which the base is added is then stirred to allow the basicization reaction to occur so that linagliptin can be produced in crystalline form. If the stirring time is longer, the production of linagliptin crystal form is poor, which leads to poor filtration, and therefore, it is preferable to stir for 5 to 30 minutes and to carry out the basic reaction.
  • the basic reaction can be reacted at 0 to 60 °C, it is preferred to react at 10 to 30 °C.
  • step (2) the step of washing in order to prevent the remaining of the acid that may remain in the linagliptin crystal form, specifically, the linagliptin crystal form obtained by filtration is washed sufficiently with water and then washed with an organic solvent.
  • the organic solvent may be heptane, hexane, diethyl ether, methyl tertiary butyl ether, isopropyl ether, and the like.
  • a more crystalline linagliptin crystal form may be obtained by washing the organic solvent.
  • the washed crystals may be dried at least 60 days in a hot air or vacuum at 60 ° C. to obtain linagliptin crystalline form.
  • the dried linagliptin crystal form may maintain the crystal form even when heated to 120 ° C.
  • the present invention provides a linagliptin 4-hydroxybenzoic acid salt represented by the formula (2) and a preparation method thereof.
  • the linagliptin 4-hydroxybenzoic acid salt may be prepared and used to obtain the linagliptin crystal form, and the method for preparing the linagliptin 4-hydroxybenzoic acid salt is as follows.
  • the linagliptin 4-hydroxybenzoic acid salt represented by Formula 2 includes (i) reacting linagliptin represented by Formula 1 with 4-hydroxybenzoic acid represented by Formula 3 in a solvent; And (ii) obtaining crystals from the solution obtained in step (i).
  • methyl alcohol, ethyl alcohol, isopropyl alcohol, water, and the like may be used, and ethyl alcohol may be preferably used.
  • Linagliptin crystal form according to the present invention exists in a single phase at room temperature, and has the form of a stable single phase required in the pharmaceutical industry by eliminating the risk of polymorphic transformation.
  • the manufacturing method is relatively simple, safe and reproducible, so that it can be applied to various commercially.
  • the present invention provides a pharmaceutical composition for treating diabetes comprising the linagliptin crystal form as an active ingredient.
  • the pharmaceutical composition may include, in addition to the active ingredient, conventional pharmaceutically acceptable carriers and / or excipients, and the like, which are conventional agents in the pharmaceutical field, for example, tablets, capsules, troches, solutions, suspensions, and the like. It may be formulated into a preparation for oral administration or a preparation for parenteral administration.
  • conventional pharmaceutically acceptable carriers and / or excipients, and the like which are conventional agents in the pharmaceutical field, for example, tablets, capsules, troches, solutions, suspensions, and the like. It may be formulated into a preparation for oral administration or a preparation for parenteral administration.
  • Solid form preparations for oral administration may be prepared by mixing one or more excipients, for example starch, calcium carbonate, sucrose, lactose, gelatin and the like.
  • excipients for example starch, calcium carbonate, sucrose, lactose, gelatin and the like.
  • lubricants such as magnesium stearate and talc may be used.
  • suspending agents, liquid solutions, emulsions, and syrups are used.
  • various excipients such as wetting agents, sweeteners, fragrances, and preservatives can be used. .
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, and the like.
  • non-aqueous solvent or suspension solvent vegetable oils such as propylene glycol, polyethylene glycol, olive oil, injectable esters such as ethyl oleate, etc. may be used, and the bases of the suppositories may be Uthepsol, macrogol, Tween 61, Cacao butter, laurin butter, glycerol, gelatin and the like can be used.
  • the human dosage of the pharmaceutical composition may vary depending on the age, weight, sex, dosage form, health condition and degree of disease of the patient, and is 0.1 to 20 mg / kg, preferably 1 to 1, based on the linagliptin active ingredient. It may be administered in several divided doses once a day to regular time intervals in an amount of 10 mg / kg.
  • the linagliptin crystalline form may be used in combination with one or more other known agents having therapeutic effects on diabetes.
  • linagliptin (Intercore Corporation) was added to the reactor, 240 ml of ethyl alcohol was added thereto, and the reaction mixture was heated to about 70 ° C., and then stirred for about 15 minutes to completely dissolve it. After the temperature of the dissolved reaction solution was adjusted to about 60 ° C., 1 equivalent of 4-hydroxybenzoic acid was added to the clear reaction solution. After stirring at the same temperature for about 4 hours, the resulting crystals were filtered off, washed with 90 ml of ethyl alcohol, and warmly dried at about 60 ° C. to obtain 34.8 g of linagliptin 4-hydroxybenzoic acid salt (yield: 90%, Purity: 88.2% (4-hydroxybenzoic acid 11.6%), melting point: 204 ⁇ ).
  • Example 20.0 g of linagliptin 4-hydroxybenzoic acid salt prepared in Example 1 was added to the reactor, and an aqueous solution in which 12.0 g of sodium hydroxide was dissolved in 300 ml of water was added. After stirring at about 25 ° C. for 15 minutes, the reaction mixture was filtered, washed with 200 ml of water, and hot-dried at about 60 ° C. to obtain 14.0 g of a solid compound (yield: 91%). Thereafter, 10 g of the solid compound was added to the reactor, and 100 ml of water was added thereto, followed by stirring at about 25 ° C. for 10 minutes.
  • reaction mixture was filtered, washed with 100 ml of water and then with 50 ml of heptane and vacuum dried at about 60 ° C. to obtain 9.29 g of linagliptin crystalline form (yield: 93%, purity: 99.8%, melting point: 202 ° C.). .
  • Test Example 1 X-ray diffraction spectrum (XRD) analysis of linagliptin crystal form
  • the melting point of each compound prepared in the Examples was measured using a melting point meter (B-545, Buchi, Switzerland).
  • the linagliptin crystal form prepared in Example is a compound represented by Chemical Formula 1, wherein 5.6, 9.8, 11.2, Endothermic peaks at 173 ° C. and 206 ° C., including peaks at diffraction angles (2 ⁇ ⁇ 0.2 °) of 11.8, 13.1, 14.4, 14.9, 16.1, 16.4, 18.4, 18.8, 19.9, 20.2, 20.7, 22.0 It can be seen that.
  • linagliptin crystal form according to the present invention has excellent thermal stability, is easy to store and maintain at room temperature, and can be usefully used as a medicine because it can be prepared as a pure polymorph.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)

Abstract

La présente invention concerne une forme cristalline de linagliptine et un procédé de préparation de cette dernière. Selon la présente invention, la forme cristalline de linagliptine présente une excellente stabilité thermique et peut être préparée de manière reproductible en une forme monocristalline, permettant ainsi une production en masse de qualité constante, et peut ainsi être utile en tant que composition pharmaceutique pour le traitement du diabète.
PCT/KR2016/010001 2015-09-17 2016-09-07 Forme cristalline de linagliptine et procédé de préparation de cette dernière Ceased WO2017047970A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2018513310A JP2018527363A (ja) 2015-09-17 2016-09-07 リナグリプチン結晶形及びこの製造方法
CN201680054246.4A CN108290891A (zh) 2015-09-17 2016-09-07 一种利格列汀晶型及其制备方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2015-0131749 2015-09-17
KR1020150131749A KR102442536B1 (ko) 2015-09-17 2015-09-17 리나글립틴 결정형 및 이의 제조방법

Publications (1)

Publication Number Publication Date
WO2017047970A1 true WO2017047970A1 (fr) 2017-03-23

Family

ID=58289234

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2016/010001 Ceased WO2017047970A1 (fr) 2015-09-17 2016-09-07 Forme cristalline de linagliptine et procédé de préparation de cette dernière

Country Status (4)

Country Link
JP (1) JP2018527363A (fr)
KR (1) KR102442536B1 (fr)
CN (1) CN108290891A (fr)
WO (1) WO2017047970A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110305131A (zh) * 2019-07-03 2019-10-08 山东百诺医药股份有限公司 利格列汀新晶型及其制备方法
US11911387B2 (en) 2010-11-15 2024-02-27 Boehringer Ingelheim International Gmbh Vasoprotective and cardioprotective antidiabetic therapy
US11911388B2 (en) 2008-10-16 2024-02-27 Boehringer Ingelheim International Gmbh Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral or non-oral antidiabetic drug
US12171767B2 (en) 2006-05-04 2024-12-24 Boehringer Ingelheim International Gmbh Uses of DPP IV inhibitors
US12178819B2 (en) 2006-05-04 2024-12-31 Boehringer Ingelheim International Gmbh DPP IV inhibitor formulations
US12312352B2 (en) 2012-05-14 2025-05-27 Boehringer Ingelheim International Gmbh Use of a DPP-4 inhibitor in SIRS and/or sepsis
US12364700B2 (en) 2016-06-10 2025-07-22 Boehringer Ingelheim International Gmbh Medical use of pharmaceutical combination or composition

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109111443A (zh) * 2018-08-28 2019-01-01 上海迪赛诺药业股份有限公司 Dpp-iv抑制剂类降糖药的新晶型及其制备方法
WO2021250995A1 (fr) * 2020-06-10 2021-12-16 有機合成薬品工業株式会社 Morphologie cristalline de 1- [(4-méthyl-quinazoline-2-yl)méthyl]-3-méthyl-7-(2-butyn-1-yl)-8-(3-(r)-amino-péperidine-1-yl)-xanthine
CN118496229A (zh) * 2024-05-13 2024-08-16 迪嘉药业集团股份有限公司 一种利格列汀新晶型及其制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012152837A1 (fr) * 2011-05-10 2012-11-15 Sandoz Ag Polymorphe de benzoate de linagliptine
US20130123282A1 (en) * 2011-11-16 2013-05-16 Leonid Metsger Solid state forms of linagliptin
WO2013128379A2 (fr) * 2012-02-27 2013-09-06 Dr. Reddy's Laboratories Limited Formes polymorphes cristallines de linagliptine
WO2014083554A1 (fr) * 2012-11-30 2014-06-05 Ranbaxy Laboratories Limited Forme amorphe stable de linagliptine
WO2015044880A1 (fr) * 2013-09-25 2015-04-02 Ranbaxy Laboratories Limited Composition pharmaceutique liquide orale d'un inhibiteur dpp-iv

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101541791B1 (ko) * 2006-05-04 2015-08-04 베링거 인겔하임 인터내셔날 게엠베하 다형태
KR20110103968A (ko) * 2008-12-23 2011-09-21 베링거 인겔하임 인터내셔날 게엠베하 유기 화합물의 염 형태
CN102372691A (zh) * 2011-11-15 2012-03-14 海门慧聚药业有限公司 (r)-3-苯二甲酰亚胺哌啶酒石酸盐的制备工艺
US9056112B2 (en) * 2011-12-28 2015-06-16 Dr. Reddy's Laboratories Limited Process for preparation of pure linagliptin
US9879011B2 (en) 2012-03-12 2018-01-30 Cadila Healthcare Limited Amorphous form of linagliptin and process for preparation thereof
IN2015DN00280A (fr) * 2012-08-13 2015-06-12 Sandoz Ag
CN104672238B (zh) * 2015-02-17 2017-12-08 华润赛科药业有限责任公司 一种利格列汀的制备方法
CN104844603A (zh) * 2015-06-05 2015-08-19 武汉理工大学 一种ⅱ型糖尿病药利格列汀的简易制备方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012152837A1 (fr) * 2011-05-10 2012-11-15 Sandoz Ag Polymorphe de benzoate de linagliptine
US20130123282A1 (en) * 2011-11-16 2013-05-16 Leonid Metsger Solid state forms of linagliptin
WO2013128379A2 (fr) * 2012-02-27 2013-09-06 Dr. Reddy's Laboratories Limited Formes polymorphes cristallines de linagliptine
WO2014083554A1 (fr) * 2012-11-30 2014-06-05 Ranbaxy Laboratories Limited Forme amorphe stable de linagliptine
WO2015044880A1 (fr) * 2013-09-25 2015-04-02 Ranbaxy Laboratories Limited Composition pharmaceutique liquide orale d'un inhibiteur dpp-iv

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12171767B2 (en) 2006-05-04 2024-12-24 Boehringer Ingelheim International Gmbh Uses of DPP IV inhibitors
US12178819B2 (en) 2006-05-04 2024-12-31 Boehringer Ingelheim International Gmbh DPP IV inhibitor formulations
US11911388B2 (en) 2008-10-16 2024-02-27 Boehringer Ingelheim International Gmbh Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral or non-oral antidiabetic drug
US11911387B2 (en) 2010-11-15 2024-02-27 Boehringer Ingelheim International Gmbh Vasoprotective and cardioprotective antidiabetic therapy
US12312352B2 (en) 2012-05-14 2025-05-27 Boehringer Ingelheim International Gmbh Use of a DPP-4 inhibitor in SIRS and/or sepsis
US12364700B2 (en) 2016-06-10 2025-07-22 Boehringer Ingelheim International Gmbh Medical use of pharmaceutical combination or composition
CN110305131A (zh) * 2019-07-03 2019-10-08 山东百诺医药股份有限公司 利格列汀新晶型及其制备方法
CN110305131B (zh) * 2019-07-03 2021-12-31 山东百诺医药股份有限公司 利格列汀新晶型及其制备方法

Also Published As

Publication number Publication date
JP2018527363A (ja) 2018-09-20
CN108290891A (zh) 2018-07-17
KR102442536B1 (ko) 2022-09-13
KR20170033684A (ko) 2017-03-27

Similar Documents

Publication Publication Date Title
WO2017047970A1 (fr) Forme cristalline de linagliptine et procédé de préparation de cette dernière
US7439252B2 (en) Ascomycin crystalline forms and preparation thereof
RU2467012C2 (ru) Способ очистки стауроспорина и способ получения n-бензоилстауроспорина
WO2011095059A1 (fr) Polymorphes du dasatinib, leurs procédés de préparation et leurs compositions pharmaceutiques
US12492214B2 (en) Solid state forms of Risdiplam and process for preparation thereof
KR20060111675A (ko) 테가세로드 염기 및 그것의 염의 다형태
US20230167156A1 (en) Solid state forms of voclosporin
EP0579681A1 (fr) Monohydrate d'hydrochlorure de tiagabine cristalline, sa preparation et son utilisation
EP0517221A1 (fr) Dérivés de arylalkylpiperidine-4-yl)méthyl]-alpha,3,4,5-tetrahydro-1-(2H)-acenaphthylene-1-one, procédé pour leurs préparations et leurs utilisations comme médicaments
EP1432681B1 (fr) Formes pseudopolymorphes de carvedilol
JP2005523874A (ja) Ｎ−〔３−（３−シアノピラゾロ〔１，５−ａ〕ピリミジン−７−イル）フェニル〕−Ｎ−エチルアセタミド（ザレプロン）の精製方法、及び当該方法により得られうるザレプロンの結晶型
KR20060015750A (ko) 지프라시돈 ＨＣｌ의 다형 형태 및 그 제조 방법
AU2002338726A1 (en) Pseudopolymorphic forms of carvedilol
WO2021060949A1 (fr) Éfinaconazole co-cristallin, et son procédé de production
US9682074B2 (en) Crystal form
WO2011152657A2 (fr) Malate d'acétyle-l-carnitine, procédé permettant de la préparer et composition pharmaceutique la comprenant
WO2009116801A2 (fr) Promédicament inhibiteur de caspase
CN100484939C (zh) 多晶型的N-(2,3-二甲基-5,6,7,8-四氢呋喃并[2,3-b]喹啉-4-基)-2-(2-氧代吡咯烷-1-基)乙酰胺
US20040097528A1 (en) Crystalline solid famciclovir forms I, II, III and preparation thereof
US12091388B2 (en) Solid state forms of Reproxalap
WO2025017530A1 (fr) Formes solides de buntanetap et leur procédé de préparation
WO2025084446A1 (fr) Forme cristalline d'un dérivé de triazolopyrimidinone
WO2024072109A1 (fr) Nouveau co-cristal d'énavogliflozine
WO2024072108A1 (fr) Nouvelle forme cristalline d'énavogliflozine et son procédé de préparation
WO2025165158A1 (fr) Composition pharmaceutique comprenant de l'hexoxyde de tétraarsenic (as4o6) pour la prévention ou le traitement du cancer de la vessie

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: 16846791

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2018513310

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: 16846791

Country of ref document: EP

Kind code of ref document: A1