WO2008000298A1 - Procédé de purification de bétaïnes - Google Patents

Procédé de purification de bétaïnes Download PDF

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Publication number
WO2008000298A1
WO2008000298A1 PCT/EP2006/063613 EP2006063613W WO2008000298A1 WO 2008000298 A1 WO2008000298 A1 WO 2008000298A1 EP 2006063613 W EP2006063613 W EP 2006063613W WO 2008000298 A1 WO2008000298 A1 WO 2008000298A1
Authority
WO
WIPO (PCT)
Prior art keywords
extraction
indocyanine green
purification
nai
betaines
Prior art date
Application number
PCT/EP2006/063613
Other languages
German (de)
English (en)
Inventor
Bernhard Dr. Hanke
Original Assignee
Pulsion Medical Systems Ag
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 Pulsion Medical Systems Ag filed Critical Pulsion Medical Systems Ag
Priority to PCT/EP2006/063613 priority Critical patent/WO2008000298A1/fr
Publication of WO2008000298A1 publication Critical patent/WO2008000298A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B67/00—Influencing the physical, e.g. the dyeing or printing properties of dyestuffs without chemical reactions, e.g. by treating with solvents grinding or grinding assistants, coating of pigments or dyes; Process features in the making of dyestuff preparations; Dyestuff preparations of a special physical nature, e.g. tablets, films
    • C09B67/0096—Purification; Precipitation; Filtration

Definitions

  • the present invention relates to a process for the purification of synthetically produced chemicals containing a betaine structure in the molecule.
  • indocyanine green a dye described in the American Pharmacopoeia.
  • Indocyanine green is 2- ⁇ 7- [1,3-dihydro-i, 1-dimethyl-3- (4-sulfobutyl) -2W-benz [e] indol-2-ylidene] -
  • Indocyanine green represents a green dye used in medicine & medicine. a is used for the diagnosis of heart, circulatory, microcirculation and liver function.
  • indocyanine green takes place, for example, by condensation of two indolinium molecules using sodium iodide.
  • the sodium iodide is added to the synthesis approach to precipitate the dye.
  • Conventional measures for reducing the Natriumiodidgeh old are complex and costly, resulting in significantly increased production cost of the dye.
  • the discontinuous Uieriiche processing of indocyanine green (ICG) with hooves of crystallization or precipitation is limited, a large-scale purification of the substance is almost impossible.
  • chromatographic methods for the purification of ICG are conceivable on a laboratory scale, larger quantities can not be cleaned in a single operation.
  • the present invention accordingly provides a process for the purification of chemical substances and chemical compounds containing a betaine structure in the 'molecule which is characterized in that reaction by-products, starting materials and / or other impurities that are insoluble in the selected organic solvent , separated by extraction.
  • the process of the invention takes advantage of the differences in solubility between the impurities and betaines.
  • the process for the purification of indocyanine green is particularly well-suited if sodium iodide (NaI) is used as the precipitation reagent in its preparation for the conversion of the acid into the corresponding Na salt.
  • NaI sodium iodide
  • indocyanine green natural substances which can be purified in this way from inorganic impurities, in particular alkaloids of the indole and isoquinoline type, are also suitable for the process according to the invention.
  • the extraction is carried out in an organic, preferably anhydrous solvent, in particular in aprotic solvents (for example CH 2 Cl 2 or ethyl acetate).
  • aprotic solvents for example CH 2 Cl 2 or ethyl acetate.
  • anhydrous solvent is used as the solvent.
  • the drying of the anhydrous solvents can be carried out in a conventional manner via molecular sieves, P 2 O 5, etc.
  • the extraction according to the invention can be carried out by shaking out (sequential extraction) or continuously.
  • the sequential extraction is usually carried out in a separatory funnel.
  • the shaking out of the substances is relatively cumbersome, time consuming and therefore less preferred.
  • the extraction is carried out continuously. Particularly suitable for this is the so-called Soxhlet extraction.
  • the material to be purified is preferably added to a sleeve permeable to the solvent or similar receiving device and continuously flushed with solvent just below its boiling point.
  • the soluble components are dissolved while leaving insoluble components in the receiver, i.e. in the purification of Indocyanin indispensable this compound is dissolved by the extraction solvent and removed from the template, while in the solvent used insoluble substances, eg. B. NaI, remain behind.
  • an indocyanine green obtained from a conventional industrial production and containing 4.6% NaI was subjected to continuous extraction in a Soxhlet apparatus.
  • anhydrous methylene chloride 500 ml of methylene chloride were dried over molecular sieves (4 ⁇ from Roth, 0.4 nm, bead form) and then distilled. 100 ml of the forerun were discarded so that about 400 ml of purified and dried methylene chloride were available for the subsequent continuous extraction.
  • the resulting indocyanine green contained ⁇ 0.4% NaI. This amount is more than 10 times lower than the tolerance specified by the USP for the parenteral use of Indocyanine Green for Injection. Extraction with solvents such as acetone resulted in extraction of NaI, which is to some extent soluble in them.

Abstract

L'invention concerne un procédé de purification de composés de synthèse possédant une structure bétaïnique dans la molécule, p. ex. de vert d'indocyanine, caractérisé en ce que les sous-produits de la réaction, les composés de départ et/ou d'autres impuretés, telles que le NaI utilisé lors du processus de production, sont éliminés par extraction.
PCT/EP2006/063613 2006-06-28 2006-06-28 Procédé de purification de bétaïnes WO2008000298A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/EP2006/063613 WO2008000298A1 (fr) 2006-06-28 2006-06-28 Procédé de purification de bétaïnes

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2006/063613 WO2008000298A1 (fr) 2006-06-28 2006-06-28 Procédé de purification de bétaïnes

Publications (1)

Publication Number Publication Date
WO2008000298A1 true WO2008000298A1 (fr) 2008-01-03

Family

ID=38068816

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2006/063613 WO2008000298A1 (fr) 2006-06-28 2006-06-28 Procédé de purification de bétaïnes

Country Status (1)

Country Link
WO (1) WO2008000298A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT107134A (pt) * 2013-08-28 2015-03-02 Mfobmx Unipessoal Lda Sistema de aperto e fixação de pedaleiro para bicicletas
CN115093362A (zh) * 2022-07-04 2022-09-23 深圳市罗素医药有限公司 一种吲哚菁绿的纯化方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2245249A (en) * 1938-10-21 1941-06-10 Eastman Kodak Co Cyclammonium quaternary salts
US2895955A (en) * 1957-06-05 1959-07-21 Eastman Kodak Co Tricarbocyanine infrared absorbing dyes
DE2046141A1 (en) * 1970-09-18 1972-03-23 Merck Patent Gmbh, 6100 Darmstadt Tricarbocyanine dyestuff mfr - using alkali alcoholate instead of sodium iodide to obtain iodine-free products
WO1995007888A1 (fr) * 1993-09-17 1995-03-23 Societe D'etudes Et De Recherches Biologiques Procede de preparation de benz[e]indoles substitues de purete elevee et leurs sels alcalins
CN1196351A (zh) * 1997-12-30 1998-10-21 河北省固安县宏峰化工有限公司 三甲铵乙内酯(甜菜碱)的合成与分离方法
WO2004078109A2 (fr) * 2003-03-07 2004-09-16 Merck Sharp & Dohme Limited Procede de synthese de produits intermediaires destines a la preparation d'antagonistes des recepteurs d'$g(a)$g(n)$g(b)3
US20040192917A1 (en) * 2003-03-31 2004-09-30 Srivastava Santosh Kumar Process for isolation of anticancer agent camptothecin from nothapodytes foetida
WO2006128451A2 (fr) * 2005-06-01 2006-12-07 Pulsion Medical Systems Ag Procede de purification de betaines

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2245249A (en) * 1938-10-21 1941-06-10 Eastman Kodak Co Cyclammonium quaternary salts
US2895955A (en) * 1957-06-05 1959-07-21 Eastman Kodak Co Tricarbocyanine infrared absorbing dyes
DE2046141A1 (en) * 1970-09-18 1972-03-23 Merck Patent Gmbh, 6100 Darmstadt Tricarbocyanine dyestuff mfr - using alkali alcoholate instead of sodium iodide to obtain iodine-free products
WO1995007888A1 (fr) * 1993-09-17 1995-03-23 Societe D'etudes Et De Recherches Biologiques Procede de preparation de benz[e]indoles substitues de purete elevee et leurs sels alcalins
CN1196351A (zh) * 1997-12-30 1998-10-21 河北省固安县宏峰化工有限公司 三甲铵乙内酯(甜菜碱)的合成与分离方法
WO2004078109A2 (fr) * 2003-03-07 2004-09-16 Merck Sharp & Dohme Limited Procede de synthese de produits intermediaires destines a la preparation d'antagonistes des recepteurs d'$g(a)$g(n)$g(b)3
US20040192917A1 (en) * 2003-03-31 2004-09-30 Srivastava Santosh Kumar Process for isolation of anticancer agent camptothecin from nothapodytes foetida
WO2006128451A2 (fr) * 2005-06-01 2006-12-07 Pulsion Medical Systems Ag Procede de purification de betaines

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Week 199910, Derwent World Patents Index; AN 1999-106746, XP002408022 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT107134A (pt) * 2013-08-28 2015-03-02 Mfobmx Unipessoal Lda Sistema de aperto e fixação de pedaleiro para bicicletas
PT107134B (pt) * 2013-08-28 2015-07-30 Mfobmx Unipessoal Lda Sistema de aperto e fixação de pedaleiro para bicicletas
CN115093362A (zh) * 2022-07-04 2022-09-23 深圳市罗素医药有限公司 一种吲哚菁绿的纯化方法

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