WO2008038094A2 - Procédé pour la préparation de l'adénosine pure - Google Patents

Procédé pour la préparation de l'adénosine pure Download PDF

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Publication number
WO2008038094A2
WO2008038094A2 PCT/IB2007/002763 IB2007002763W WO2008038094A2 WO 2008038094 A2 WO2008038094 A2 WO 2008038094A2 IB 2007002763 W IB2007002763 W IB 2007002763W WO 2008038094 A2 WO2008038094 A2 WO 2008038094A2
Authority
WO
WIPO (PCT)
Prior art keywords
adenosine
process according
solution
purity
pure
Prior art date
Application number
PCT/IB2007/002763
Other languages
English (en)
Other versions
WO2008038094A3 (fr
Inventor
Anjum Reyaz Khan
Nagesh Devidasrao Limbekar
Arvind Yenkatesha Merwade
Mohammed Jaweed Mukarram Siddiqui
Original Assignee
Wockhardt Research Centre
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 Wockhardt Research Centre filed Critical Wockhardt Research Centre
Publication of WO2008038094A2 publication Critical patent/WO2008038094A2/fr
Publication of WO2008038094A3 publication Critical patent/WO2008038094A3/fr

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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
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals

Definitions

  • the field of the invention relates to a process for the preparation of pure adenosine.
  • the invention also relates to pharmaceutical compositions that include the pure adenosine.
  • adenosine is 9- ⁇ -D-Ribofuranosyl-9H-purin-6-amine of structural Formula I. It is also known by other names. It is indicated for the treatment of the signs and symptoms of arrhythmia, hyperlipemia and cardiac infarction.
  • Adenosine is a naturally occurring nucleoside composed of the purine, adenine, and the sugar, D-ribose. In addition, it is commonly present in the body in the form of adenosine monophosphate (AMP), adenosine diphosphate (ADP) and adenosine triphosphate (ATP). Adenosine is manufactured from yeast nucleic acid.
  • AMP adenosine monophosphate
  • ADP adenosine diphosphate
  • ATP adenosine triphosphate
  • the present inventors have now developed an efficient process to get the adenosine of high purity.
  • the process of present invention is cost-effective and easily scalable at commercial scale.
  • a process for preparing pure adenosine having a purity of 99.9% w/w or more when measured by HPLC includes obtaining a suspension or a solution of adenosine in one or more solvents; contacting the suspension or solution with a base to get a solution; and recovering the pure adenosine from the solution thereof by the removal of the solvent.
  • the process may include further drying of the product obtained.
  • the process may produce the pure adenosine having a purity of 99.5% w/w or more when measured by HPLC. In particular, it may produce the pure adenosine having purity 99.9% w/w or more.
  • a pharmaceutical composition that includes a therapeutically effective amount of pure adenosine having purity 99.9% w/w or more; and one or more pharmaceutically acceptable carriers, excipients or diluents.
  • the inventors have developed a process for the preparation of pure adenosine, by obtaining a suspension or a solution in one or more solvents; contacting the suspension or solution with a base to get a mixture; heating the resultant mixture; and recovering the pure adenosine from the solution thereof by the removal of the solvent.
  • compositions that contain the pure adenosine having purity 99.9% w/w or more, in admixture with one or more solid or liquid pharmaceutical diluents, carriers, and/or excipients.
  • the solution of adenosine may be obtained by dissolving in a suitable solvent.
  • a suitable solvent such a solution may be obtained directly from a reaction in which adenosine is formed.
  • the solvent containing adenosine may be heated to obtain a solution. It can be heated from about 30 0 C to about reflux temperature of the solvent used, for example from about 30 0 C to about 100 0 C.
  • obtaining includes dissolving, slurrying, stirring or a combination thereof.
  • the pure adenosine may be recovered from the solution by a technique which includes, for example, filtration, filtration under vacuum, evaporation, decantation, and centrifugation.
  • suitable solvents includes any solvent or solvent mixture in which adenosine can be solubilized, including, for example, water, alcohols, ketones, and mixtures thereof.
  • a suitable alcohol includes one or more of methanol, ethanol, and isopropanol.
  • ketones include acetone and methyl isobutyl ketone.
  • the adenosine may be prepared by any of the methods known in the art. In particular, it may be prepared by using the reactions and techniques described in Journal of medical chemistry, 30(6), 982-991 , (1987).
  • the adenosine may contain impurities, which may arise during production or storage, such as degradation products.
  • Adenosine can be prepared by methods known in the art.
  • the said adenosine containing impurities in the form of solution or suspension was treated with base at higher temperature.
  • the mass is cooled and the separated product was isolated.
  • the product obtained was dried to get pure adenosine having HPLC purity of 99.5 % or more.
  • the base may be organic or inorganic.
  • base examples include sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, triethylamine, methylamine, ammonia, and ammonia solution.
  • 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 Dryer.
  • the pure adenosine has a purity of 99.5% w/w or more. More particularly, the purity of adenosine is 99.9% w/w or more.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)

Abstract

L'invention concerne un procédé pour la préparation de l'adénosine pure. L'invention concerne également des compositions pharmaceutiques qui comprennent de l'adénosine pure.
PCT/IB2007/002763 2006-09-29 2007-09-24 Procédé pour la préparation de l'adénosine pure WO2008038094A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1585/MUM/2006 2006-09-29
IN1585MU2006 2006-09-29

Publications (2)

Publication Number Publication Date
WO2008038094A2 true WO2008038094A2 (fr) 2008-04-03
WO2008038094A3 WO2008038094A3 (fr) 2011-05-19

Family

ID=39230582

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2007/002763 WO2008038094A2 (fr) 2006-09-29 2007-09-24 Procédé pour la préparation de l'adénosine pure

Country Status (1)

Country Link
WO (1) WO2008038094A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008038094A3 (fr) * 2006-09-29 2011-05-19 Wockhardt Research Centre Procédé pour la préparation de l'adénosine pure

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6566371B2 (en) * 2000-04-28 2003-05-20 University Of Pittsburgh Intraperitoneal administration of adenosine for the treatment of prevention of gastrointestinal of systemic diseases

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008038094A2 (fr) * 2006-09-29 2008-04-03 Wockhardt Research Centre Procédé pour la préparation de l'adénosine pure

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6566371B2 (en) * 2000-04-28 2003-05-20 University Of Pittsburgh Intraperitoneal administration of adenosine for the treatment of prevention of gastrointestinal of systemic diseases

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHIRAKUL ET AL.: 'Preparation of Base-Deuterated 2'-Deoxyadenosine Nucleosides and their Site-Specific Incorporation into DNA, .' NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS, [Online] vol. 20, no. 12, 31 December 2001, pages 1903 - 1913 Retrieved from the Internet: <URL:http://pdfserve.informaworld.com/839439_713642851.pdf> *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008038094A3 (fr) * 2006-09-29 2011-05-19 Wockhardt Research Centre Procédé pour la préparation de l'adénosine pure

Also Published As

Publication number Publication date
WO2008038094A3 (fr) 2011-05-19

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