WO2005030698A1 - Procede de preparation de voglibose - Google Patents

Procede de preparation de voglibose Download PDF

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Publication number
WO2005030698A1
WO2005030698A1 PCT/IB2004/003120 IB2004003120W WO2005030698A1 WO 2005030698 A1 WO2005030698 A1 WO 2005030698A1 IB 2004003120 W IB2004003120 W IB 2004003120W WO 2005030698 A1 WO2005030698 A1 WO 2005030698A1
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WO
WIPO (PCT)
Prior art keywords
voglibose
acid
pure
crystalline
hydrochloride
Prior art date
Application number
PCT/IB2004/003120
Other languages
English (en)
Inventor
Chandra Has Khanduri
Jayachandra Suresh Babu
Purna Chandra Ray
Jigar Bhaskarbhai Shah
Yatendra Kumar
Original Assignee
Ranbaxy Laboratories Limited
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 Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Publication of WO2005030698A1 publication Critical patent/WO2005030698A1/fr

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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
    • A61K31/13—Amines
    • A61K31/133—Amines having hydroxy groups, e.g. sphingosine
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/10—Separation; Purification; Stabilisation; Use of additives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
    • C07C215/42—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups or hydroxy groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C215/44—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having amino groups or hydroxy groups bound to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton bound to carbon atoms of the same ring or condensed ring system

Definitions

  • the field of the invention relates to processes for the preparation of pure voglibose.
  • the invention also relates to the preparation of acid addition salts of voglibose. More particularly, it relates to the preparation of crystalline hydrochloride salt of voglibose.
  • the invention also relates to pharmaceutical compositions that include the pure voglibose or crystalline voglibose hydrochloride and use of said compositions for treatment or prevention of hyperglycemic symptoms and various disorders caused by hyperglycemia such as diabetes, obesity, adiposity, and hyperlipemia.
  • voglibose is (lS)-(l(OH),2,4,5/l,3)-5-[[2-hydroxy-l- (hydroxymethyl) ethyl]amino]-l-C-(hydroxymethyl)-l,2,3,4-cyclohexanetetrol, which has an excellent inhibitory activity against glucoside hydrolase.
  • Several processes have been reported for the preparation of voglibose for example, in U.S. Patent Nos. 4,701,559; 4,824,943; 4,898,986; and 6,150,568; J Org. Chem., 1992, 57, 3651 andJ Med. Chem., 1986, 29, 1038.
  • a pure voglibose in one general aspect there is provided a pure voglibose.
  • the pure voglibose may have the X-ray diffraction pattern of Figure IV, infrared spectrum of Figure V, and differential scanning calorimetry plot of Figure VI.
  • a process for preparing pure voglibose includes obtaining a solution of voglibose in one or more solvents; contacting the solution with an acid; isolating voglibose acid addition salt in a solid state; and converting the voglibose acid addition salt into pure voglibose.
  • the process may include further drying of the product obtained.
  • a pharmaceutical composition that includes a therapeutically effective amount of pure voglibose; and one or more pharmaceutically acceptable carriers, excipients or diluents.
  • a method for treating or preventing a disease caused by hyperglycemia such as diabetes, obesity, adiposity, and hyperlipemia in a warm-blooded animal, the method comprising providing a pharmaceutical composition to the warm-blooded animal that includes the pure voglibose.
  • a crystalline hydrochloride salt of voglibose i.e. voglibose hydrochloride.
  • the voglibose hydrochloride may have the X-ray diffraction pattern of Figure I, infrared spectrum of Figure II, and differential scanning calorimetry plot of Figure III.
  • a process for preparing voglibose hydrochloride includes obtaining a solution of voglibose in one or more solvents; contacting the solution with hydrogen chloride; and isolating the voglibose hydrochloride in the crystalline form.
  • a pharmaceutical composition that includes a therapeutically effective amount of crystalline voglibose hydrochloride; and one or more pharmaceutically acceptable carriers, excipients or diluents.
  • a method for treating or preventing a disease caused by hyperglycemia such as diabetes, obesity, adiposity, and hyperlipemia in a warm-blooded animal comprising providing a pharmaceutical composition to the warm-blooded animal that includes the crystalline voglibose hydrochloride.
  • Figure III is differential scanning calorimetry plot of voglibose hydrochloride.
  • Figure TV is X- ray powder diffraction pattern of voglibose.
  • Figure V is an infrared spectrum of voglibose.
  • Figure VI is differential scanning calorimetry plot of voglibose.
  • the inventors have developed a process for the preparation of pure voglibose, by preparing a solution of voglibose in one or more solvents; contacting the solution with an acid; isolating voglibose acid addition salt in a solid state; and converting the voglibose acid addition salt into pure voglibose.
  • compositions that contain the pure voglibose, in admixture with one or more solid or liquid pharmaceutical diluents, carriers, and/or excipients.
  • the solution of voglibose may be obtained by dissolving voglibose in a suitable solvent. Alternatively, such a solution may be obtained directly from a reaction in which voglibose is formed. The solvent containing voglibose may be heated to obtain a solution.
  • the voglibose may be prepared by any of the methods known in the art including those described in U.S. Patent Nos. 4,701,559; 4,824,943; 4,898,986; and 6,150,568; J Org.
  • suitable solvents includes any solvent or solvent mixture in which voglibose can be solubilized, including, for example, water, alcohols, ketones, nitriles, chlorinated hydrocarbons, dipolar aprotic solvents, esters, cyclic ethers, and mixtures thereof.
  • a suitable alcohol includes one or more of methanol, ethanol, and isopropanol. Examples of ketones include acetone and methyl isobutyl ketone.
  • nitrile examples include acetonitrile.
  • a suitable chlorinated hydrocarbon includes one or more of chloroform, dichloromethane, and 1,2-dichloroethane.
  • dipolar aprotic solvents include solvents such as dimethylsulfoxide and dimethylformamide.
  • esters include solvents such as methyl acetate, ethyl acetate, and isopropyl acetate.
  • cyclic ethers include solvents such as dioxane and tetrahydrofuran. Mixtures of all of these solvents are also contemplated.
  • the solution of voglibose in a solvent can be obtained by dissolving, slurrying, stirring or a combination thereof.
  • the conversion of voglibose into acid addition salt of voglibose can be carried out by adding organic or an inorganic acid.
  • the acid may be added to a solution of voglibose in a suitable solvent.
  • acid may be added in the last step for the preparation of voglibose and acid addition salt of voglibose may be isolated directly without isolating the voglibose.
  • inorganic acids include hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid and nitric acid.
  • Examples of organic acids include formic acid, acetic acid, maleic acid, malic acid, oxalic acid, tartaric acid, citric acid, ascorbic acid, mandelic acid, p-toluenesulfonic acid and methane sulfonic acid.
  • Isolating the acid addition salt of voglibose includes one or more of distillation, distillation under vacuum, crystallization, precipitation, cooling, filtration, filtration under vacuum, decantation and centrif ⁇ gation.
  • the precipitation of acid addition salt of voglibose may be spontaneous, depending upon the solvent and the conditions used.
  • the precipitation may also be facilitated by adding seeds of the desired salt or by adding an anti-solvent, i.e.
  • a solvent in which acid addition salt of voglibose is insoluble or sparingly soluble, to the solvent in which acid addition salt of voglibose is prepared may be insoluble or sparingly soluble, to the solvent in which acid addition salt of voglibose is prepared.
  • precipitation may also be induced by distilling off some solvent and/or reducing the temperature.
  • the acid addition salt may be recrystallized one or more times before conversion to voglibose, to get higher purity.
  • anti-solvents that may be added to precipitate out acid addition salt of voglibose include hydrocarbons such as hexane, cyclohexane, toluene, heptane and octane; lower alkyl ethers such as diethylether and diisopropylether and mixtures thereof.
  • the conversion of acid addition salts of voglibose to pure voglibose may be achieved by adding a base in a suitable solvent.
  • the base may be organic or inorganic.
  • organic bases include trimethylamine, triethylamine, tributylamine, triisopropylamine, diisopropylethylamine, pyridine, morpholine, DBU (1,8- diazabicyclo- [5.4.0]-undec-7-ene), DBN (l,5-diazabicyclo-[4.3.0]-non-5-ene), 4- dimethylamino pyridine and mixtures thereof.
  • inorganic bases include alkali metal carbonate, bicarbonate, hydroxide and mixtures thereof.
  • alkali metal carbonate examples include lithium carbonate, sodium carbonate and potassium carbonate.
  • alkali metal bicarbonate examples include sodium bicarbonate and potassium bicarbonate.
  • alkali metal hydroxide examples include sodium hydroxide and potassium hydroxide.
  • the solvents used for the conversion of acid addition salts of voglibose to pure voglibose may be the same as those described above for the preparation of voglibose acid addition salts.
  • the product obtained may be further or additionally dried to achieve the desired moisture values.
  • the product may be further or additionally dried in a tray drier, dried under vacuum and/or in a Fluid Bed Drier.
  • the pure voglibose has a purity of more than 99%.
  • the purity of voglibose is more than 99.5%, for example more than 99.8%.
  • the inventors have found a novel crystalline form of voglibose hydrochloride.
  • the crystalline form is characterized by its X-ray powder diffraction pattern as shown in Figure I, infrared spectrum as shown in Figure II, and differential scanning calorimetry plot as shown in Figure III.
  • the crystalline voglibose hydrochloride may be characterized by X- ray diffraction peaks at about 17.70, 20.20, 22.84 and 26.78 ⁇ 0.2 degrees two-theta.
  • the inventors also have developed a process for the preparation of the crystalline form of voglibose hydrochloride, by obtaining a solution of voglibose in one or more solvents; contacting the solution with hydrogen chloride; and isolating the voglibose hydrochloride in the crystalline form.
  • the inventors also have developed pharmaceutical compositions that contain crystalline voglibose hydrochloride, in admixture with one or more solid or liquid pharmaceutical diluents, carriers, and/or excipients.
  • the pure voglibose may be obtained from crystalline voglibose hydrochloride in a manner similar to that described above for the preparation of voglibose from acid addition salts of voglibose.
  • the solution of voglibose may be obtained by dissolving voglibose in one or more solvents. Alternatively, such a solution may be obtained directly from a reaction in which voglibose is formed.
  • the voglibose may be prepared by any of the methods known in the art including those described in U.S. Patent Nos. 4,701,559; 4,824,943; 4,898,986; and 6,150,568; J. Org.
  • the voglibose may also be obtained as a solution directly from a reaction in which voglibose is formed and used as such without isolation.
  • the solution of voglibose in a solvent can be obtained by dissolving, slurrying, stirring or a combination thereof.
  • the hydrogen chloride may be added to a solution of voglibose in a suitable solvent.
  • the hydrogen chloride may be added in the last step for the preparation of voglibose and voglibose hydrochloride in the crystalline form may be isolated directly without isolating the voglibose.
  • Isolating the voglibose hydrochloride in the crystalline form includes one or more of distillation, distillation under vacuum, crystallization, precipitation, cooling, filtration, filtration under vacuum, decantation and centrifugation.
  • the hydrogen chloride used in the salt formation process may be an aqueous solution or in gaseous form.
  • the aqueous solution of hydrogen chloride is commercially available.
  • the gaseous hydrogen chloride may be obtained commercially or prepared by the methods known in art.
  • the gaseous hydrogen chloride may be dissolved in a suitable solvent.
  • the solvents used for the preparation of voglibose hydrochloride may be similar to those used for the preparation of acid addition salts of voglibose as described above.
  • the product obtained may be further or additionally dried.
  • the product may be further or additionally dried in a tray drier, dried under vacuum and/or in a Fluid Bed Drier.
  • the resulting crystalline voglibose hydrochloride may be formulated into ordinary dosage forms such as, for example, tablets, capsules, pills, solutions, etc.
  • the medicaments can be prepared by conventional methods with conventional pharmaceutical excipients.
  • the voglibose hydrochloride can be administered for the prevention and treatment of hyperglycemic symptoms and various disorders caused by hyperglycemia such as obesity, adiposity, hyperlipemia (arteriosclerosis), and diabetes in a warmblooded animal.
  • a warm-blooded animal is a member of the animal kingdom possessed of a homeostatic mechanism and includes mammals and birds.
  • the salt is generally administered as part of a pharmaceutical composition with a pharmaceutically acceptable carrier, diluent or excipient and optionally other therapeutic ingredients.
  • the salt may be conventionally formulated into tablets, capsules, suspensions, dispersions, injectables and other pharmaceutical forms. Any suitable route of administration may be employed for example, peroral or parenteral.
  • the present invention is further illustrated by the following examples which are provided merely to be exemplary of the invention and are not intended to limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
  • 2-amino-l,3-propanediol (20. lg, 220 mmol) was added to a solution of tetra-O-benzyl- 5-oxo-l-C-(hydroxymethyl)-l,2,3,4-cyclohexanetetrol (35.0 g, 63.4 mmol) in methanol (350 ml) at ambient temperature and stirred for 60 minutes.
  • Sodium cyanoborohydride 14 g, 222 mmol
  • Concentrated hydrochloric acid was added to adjust pH to about 8.0 and the reaction mixture was stirred overnight.
  • the reaction mixture was partitioned between water and ethyl acetate. Ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated to obtain title compound as pale yellow color syrup.

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

Abstract

L'invention concerne des procédés de préparation de voglibose pur et la préparation de sels d'addition acide de voglibose. Plus spécifiquement, elle concerne la préparation du chlorhydrate cristallin de voglibose. L'invention concerne également des compositions pharmaceutiques qui contiennent du voglibose pur ou du chlorhydrate de voglibose et l'utilisation de ces compositions pour traiter ou prévenir les symptômes hyperglycémiants et différents troubles provoqués par l'hyperglycémie, tels que le diabète, l'obésité et l'hyperlipidémie.
PCT/IB2004/003120 2003-09-26 2004-09-24 Procede de preparation de voglibose WO2005030698A1 (fr)

Applications Claiming Priority (2)

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IN1210DE2003 2003-09-26
IN1210/DEL/2003 2003-09-26

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005092834A1 (fr) * 2004-03-29 2005-10-06 Ranbaxy Laboratories Limited Procedes pour la purification de la voglibose et de ses intermediaires
JP2007277238A (ja) * 2006-04-05 2007-10-25 Hanmi Pharm Co Ltd ボグリボースの製造方法
WO2008011791A1 (fr) * 2006-07-17 2008-01-31 Pharmaxyn Laboratories Ltd. Voglibose tetrabenzyle cristallin et procédé de préparation associé
US20140018391A1 (en) * 2012-04-20 2014-01-16 Ono Pharmaceutical Co., Ltd. Methods of Producing Anamorelin Hydrochloride Having Controlled Chloride Content

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101279925B (zh) * 2008-05-30 2011-10-19 雷云 四苄基伏格列波糖盐及其制备方法和应用
CN105963280B (zh) * 2016-06-30 2018-11-06 合肥华方医药科技有限公司 一种伏格列波糖口腔速溶膜及其制备方法
CN111855841B (zh) * 2020-06-30 2022-06-14 辰欣药业股份有限公司 一种伏格列波糖原料及制剂中有关物质的测定方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4898986A (en) * 1986-09-09 1990-02-06 Takeda Chemical Industries, Ltd. Inosose derivatives, production and use thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4898986A (en) * 1986-09-09 1990-02-06 Takeda Chemical Industries, Ltd. Inosose derivatives, production and use thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
HIROSHI FUKASE AND SATOSHI HORII: "Synthesis of Valiolamine and Its N-Substituted Derivatives AO-128, Validoxylamine G, and Validamycin G via Branched-Chain Inosose Derivatives", J. ORG. CHEM., vol. 57, no. 13, 1992, pages 3651 - 3658, XP002317080 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005092834A1 (fr) * 2004-03-29 2005-10-06 Ranbaxy Laboratories Limited Procedes pour la purification de la voglibose et de ses intermediaires
JP2007277238A (ja) * 2006-04-05 2007-10-25 Hanmi Pharm Co Ltd ボグリボースの製造方法
WO2008011791A1 (fr) * 2006-07-17 2008-01-31 Pharmaxyn Laboratories Ltd. Voglibose tetrabenzyle cristallin et procédé de préparation associé
CN100393694C (zh) * 2006-07-17 2008-06-11 深圳市药兴生物科技开发有限公司 四苄基伏格列波糖的结晶及制备方法
KR101379988B1 (ko) 2006-07-17 2014-04-01 파마신 라보라토리스 엘티디. 결정상의 테트라벤질 보글리보스 및 그의 제조방법
US20140018391A1 (en) * 2012-04-20 2014-01-16 Ono Pharmaceutical Co., Ltd. Methods of Producing Anamorelin Hydrochloride Having Controlled Chloride Content
US9872883B2 (en) 2012-04-20 2018-01-23 Helsinn Healthcare Sa Methods of producing anamorelin hydrochloride having controlled chloride content
US9956261B2 (en) 2012-04-20 2018-05-01 Helsinn Healthcare Sa Methods of producing anamorelin hydrochloride having controlled chloride content
US9981002B2 (en) 2012-04-20 2018-05-29 Helsinn Healthcare Sa Methods of producing anamorelin hydrochloride having controlled chloride content
US10300105B2 (en) 2012-04-20 2019-05-28 Ono Pharmaceutical Co., Ltd Methods of producing anamorelin hydrochloride having controlled chloride content
US10576122B2 (en) 2012-04-20 2020-03-03 Helsinn Healthcare Sa Methods of producing anamorelin hydrochloride having controlled chloride content
US10905737B2 (en) 2012-04-20 2021-02-02 Helsinn Healthcare Sa Methods of producing anamorelin hydrochloride having controlled chloride content

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