WO1999036460A1 - Composes susceptibles de pieger les ions metalliques, procede les mettant en oeuvre, et leur utilisation - Google Patents
Composes susceptibles de pieger les ions metalliques, procede les mettant en oeuvre, et leur utilisation Download PDFInfo
- Publication number
- WO1999036460A1 WO1999036460A1 PCT/FR1999/000103 FR9900103W WO9936460A1 WO 1999036460 A1 WO1999036460 A1 WO 1999036460A1 FR 9900103 W FR9900103 W FR 9900103W WO 9936460 A1 WO9936460 A1 WO 9936460A1
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- WO
- WIPO (PCT)
- Prior art keywords
- formula
- mixture
- group
- diamine
- polyamines
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G73/00—Macromolecular compounds obtained by reactions forming a linkage containing nitrogen with or without oxygen or carbon in the main chain of the macromolecule, not provided for in groups C08G12/00 - C08G71/00
- C08G73/02—Polyamines
- C08G73/0206—Polyalkylene(poly)amines
Definitions
- the present invention relates to compounds having a high capacity for retaining metal ions and their anions present in aqueous media.
- the complexing yield must be high and, if possible, easy salting out to recover the trapped ions on the one hand and on the other hand recycle the compounds used.
- the objectives are therefore the following:
- the invention relates to compounds chosen from:
- - A represents a (CC 6 ) alkylene or alkylidene, optionally substituted by one or more carboxyls; a group (CH 2 ) - - C -; a group
- R t represents hydrogen or a (CrC ⁇ alkyl optionally substituted by one or more carboxyls and / or an imidazolyl, either by polymerization on itself of a molecule comprising both a primary amine function and a aldehyde function protected in acetal form, either by reduction of a polyamide by a powerful reducing agent such as lithium aluminum hydride;
- Z independently represent a diamine of formula (1) or a polyamine or a mixture of polyamines as defined above; Z can also represent a carrier molecule such as polylysine and bovine serum albumin;
- - p is an integer varying from 1 to 3.
- (C 1 -C 6 ) alkyl is meant the methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, i-pentyl groups, t-pentyl and hexyl.
- (C ⁇ -C 6 ) alkylene or alkylidene is meant the monovalent or divalent radicals corresponding to the CC 6 alkyl groups.
- the invention therefore relates to the conjugates of formula XYZ where Y represents succinic or glutaric anhydride, Z represents polylysine and X represents a diamine of formula ⁇ NA-NHR ! in which
- the diamine of formula (1) is chosen from:
- the polyamines according to the invention comprise one or more repeating units of formula (1).
- the invention therefore relates equally well to homopolyamines such as, for example, poly (L-ornithine), poly (putrescine), poly (cadaverine), poly (L-carnosine), poly (spermidine) or poly ( spermine) than copolyamines such as, for example, spermine / spermidine / cadaverine / L-camosine copolyamines; spermine / spermidine / cadaverine; spermine / spermidine; spermine / spermidine; spermine / cadaverine / L-carnosine; spermine / cadaverine / putrescine / L-carnosine; or even spermine / spermidine / putrescine / L-omithine.
- copolyamines such as, for example, spermine / spermidine / cadaverine / L-camosine copolyamines; spermine / sperm
- the copolyamines can also comprise an amino acid such as tryptophan, cysteine or tyrosine, such as for example the spermine / L-carnosine / cysteine copolymer, or alternatively a molecule having at least one group amino.
- the compound according to the invention is a mixture of polyamines, in particular a mixture of homopolyamines, and preferably a mixture of poly (L-ornithine), poly (putrescine), poly (cadaverine), poly (spermidine) and poly (spermine).
- Other preferred compounds according to the invention include the conjugates of formula XYZ where X represents a diamine of formula (1), Y represents the residue of succinic or glutaric anhydride and Z represents a mixture of polyamines as defined above .
- X advantageously represents poly (L-ornithine) or poly (L-carnosine) and Z represents spermidine or spermine.
- the polyamines in accordance with the invention can be obtained by polymerization of a crosslinking agent such as formaldehyde, giyoxal, malonaldehyde, 1, 1, 3,3-tetramethoxypropane or glutaraldehyde, and a diamine of formula (1) or a mixture of diamines of formula (1).
- a crosslinking agent such as formaldehyde, giyoxal, malonaldehyde, 1, 1, 3,3-tetramethoxypropane or glutaraldehyde
- a diamine of formula (1) or a mixture of diamines of formula (1) for example, the polymerization can be carried out according to the following three-step protocol: 1st step:
- 3rd step The purification of the polyamines is carried out by dialysis: * 1st dialysis against water with NaBH 4 to complete the reduction; * then 2 other dialyses against water without NaBH 4 .
- the polymerization can also be carried out from m molecules of 1, 1, 3,3-tetramethoxypropane and from m molecules comprising two primary amines such as ethylene diamine or a polyamine:
- polymerization can be carried out from aminoacetaldehyde-diethylacetal:
- the protocol used is as follows: protected from light, 100 mg of acetal are dissolved in 2 ml of water and 200 ⁇ l of 4N HCl; the mixture is placed in an oven at 37 ° C. with stirring for 30 minutes. 4 ml of 3M pH 8 acetate are added. The mixture is placed in an oven at 37 ° C., with stirring, for 2 hours.
- the imine reduction and purification steps are carried out in the same manner as in the glutaraldehyde polymerization.
- the conjugates of formula XYZ according to the present invention can be obtained by coupling methods well known to those skilled in the art, between a functional group of each of the molecules X and Z, optionally via succinic or glutaric anhydride . Examples of coupling agent which can be used for the purposes of the invention include, in particular, carbodiimide, ethyl chloroformate or hexamethylene diisocyanate.
- the compound Y is for example glutarylated or succinylated in the following way: 10 mg of the compound Y are dissolved in 1 ml of water [or 200 ⁇ l of dimethylsulfoxide (DMSO) and 800 ⁇ l of water], 8 are added, 5 mg of succinic or glutaric anhydride and 85 ⁇ l of 1N sodium hydroxide by vortexing the mixture. At the end of this step, the solution is frozen and lyophilized.
- the freeze-dried product is the compound: Y-succinylated or Y-glutarylated with a free carboxyl which can be activated with carbodiimide (aqueous medium) or with ethyl chloroformate (ECF, anhydrous solvent).
- the Y-succinylated or Y-glutarylated product is attached to the X-Z assembly.
- the final compound is purified by dialysis (s) against equilibrium water.
- Z represents polylysine or bovine serum albumin
- the compounds according to the present invention have an excellent ability to trap metal ions in solution by forming a coordination complex with said ions.
- the invention relates to a method for recovering metal ions in solution, which comprises the following steps: - bringing a solution containing metal ions into contact with a compound as defined above for form a complex;
- a dialysis apparatus As a filtration device, a dialysis apparatus, an ultrafiltration membrane or preferably an affinity chromatography column are advantageously used. In the latter case, it is necessary that the pH of the column is maintained at a value greater than or equal to 8 during the passage of the complex in order to maintain the -NH- or -NH 2 groups of the diamines and / or polyamines under this form.
- the metal ions are recovered by adding to the dyalisate a solution of a mineral acid such as hydrochloric acid or an organic acid buffer such as a glycine buffer, or washing of the membrane or of the column by such a solution.
- Another advantage of the process according to the invention lies in the fact that it is possible to regenerate the compounds used, in particular by treating the filter used with a buffer solution whose pH is greater than or equal to 7.4.
- the process according to the invention is therefore both simple and economical. Thanks to their properties, the compounds according to the invention can be used in different applications, for example:
- G reduced glutaraldehyde residue MDA: para, para'-methylenedianiline blend 1: poly (ORN-G) + poly (PU-G) + poly (CD-G) + poly (SPD-G) + poly (SPM-G ) blend 2: poly (SPD-G) + poly (SPM-G)
- ORN L-omithine PL: poly-L-lysine PU: putrescine SPD: spermidine SPM: spermine
- EXAMPLE 1 Filtration by dialysis 1 - Piéqeaqe / salargage du cuiyre a) - 2 ml of a solution containing copper sulphate, brought into contact with a compound according to the invention, are dialysed against water (liter). A sample of the dialysate is taken to the Departmental Laboratory for Water Analysis in Pau to quantify the quantity of metallic ion released.
- the quantity of Cu2 + ion released was determined according to the techniques used at the departmental laboratory for water analysis in Pau: the CDERE. In this laboratory, we used the methods of quantification of ions called:
- CD-AG-mixture 1 CD-AG-mixture 1; CARN-AG-PL and PU- AG-mixture 1.
- a large part of the Cu 2+ trapped by the mixture 2 is released after acid treatment.
- the mixture 2 is pH-sensitive, therefore after treatment allows recycling of the retained ions.
- Polyamines can be reused after washing in buffer solutions with a pH> 7.4.
- the ratio of the copper concentration of the ultrafiltered solution to the initial copper concentration (Cf / Ci) increases as the ultrafiltered volume (V) increases.
- the column consists of 2 g of Sepharose gel activated with cyanogen bromide (REF: Pharmacia Code N ° 17-0430-01) to which a mixture of polyamines (mixture 1) has been fixed.
- REF Pharmacia Code N ° 17-0430-01
- the volume of the column is 7.4 ml.
- the concentration of sample 4 which corresponds to 800 ml of water filtered on the column, is 61.22 ⁇ g / l. It gives us the quantity of Cu 2+ retained by the column, 2.351 mg and the percentage of Cu + retained is therefore 97.95%.
- the concentration of sample 5, which corresponds to the elution, is 43.94 mg / l. It gives us the quantity of Cu released, 2.197 mg.
- the flow rate of the column is 500 ml / h
- the Cu 2+ concentration is divided by 1969.2 between the outlet water and that to be decontaminated, which confirms the need for coupling with the Tris to maintain a pH above 8 in order to maintain the NH 2 and NH groups under this form.
- the Zn + concentration of the filtered solution (sample 7.7) is 14.36 mg / l. So the amount of Zn 2+ that was captured is 7.23 mg. It is noted that for the Zn 2+ ions it is necessary to increase the amount of Tris fixed on the gel in order to have a slower decrease in pH and to obtain a good yield for trapping these ions. 3.3 - conclusion - the column system is applicable in an industrial environment. Its cost is low in comparison with the means available to manufacturers today, such as ion exchange resins;
- copolyamine having the highest number of NH and NH2 has a higher buffering capacity, therefore here copolyamine 5 which corresponds to the copolyamine on which spermine has been coupled with the carbodiimide.
- copolyamine 5 which corresponds to the copolyamine on which spermine has been coupled with the carbodiimide.
- a pH test is carried out between copolyamine 5 and mixture 2, which so far has had the strongest buffering capacity.
- the polyamine which has the most important buffering capacity is copolyamine
- the encephalitogenic peptide has the following sequence:
- the rats came from the January Breeding Center. During all the experiments, the animals were put under the breeding conditions required by legislation. The rats are injected with the encephalitogenic mixture (PE and Mycobacterium) and then distributed randomly in each group.
- PE and Mycobacterium encephalitogenic mixture
- the animals were observed clinically every working day after administration of the encephalitogenic emulsion.
- the tests are based on a few criteria relating to:
- the average weight development of the group treated with the 0.7 W 0.3 -G SPD copolymer is not different from that of the control group.
- the advantage of the SPDo copolymer, W 0 ⁇ 3 - G is confirmed: the compound is not sufficient to abolish the brain attack, but it reduces it by half in its intensity and its duration . Here it was administered 12 days before the onset of the attack.
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
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- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99900962A EP1049736A1 (fr) | 1998-01-20 | 1999-01-20 | Composes susceptibles de pieger les ions metalliques, procede les mettant en oeuvre, et leur utilisation |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9800547A FR2773808B1 (fr) | 1998-01-20 | 1998-01-20 | Composes susceptibles de pieger les ions metalliques, leur procede d'obtention et leur utilisation |
FR98/00547 | 1998-01-20 |
Publications (1)
Publication Number | Publication Date |
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WO1999036460A1 true WO1999036460A1 (fr) | 1999-07-22 |
Family
ID=9521937
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FR1999/000103 WO1999036460A1 (fr) | 1998-01-20 | 1999-01-20 | Composes susceptibles de pieger les ions metalliques, procede les mettant en oeuvre, et leur utilisation |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP1049736A1 (fr) |
FR (1) | FR2773808B1 (fr) |
WO (1) | WO1999036460A1 (fr) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006512435A (ja) * | 2002-12-24 | 2006-04-13 | ゲマック | 有効成分の拡散の分野において適用できる活性分子のベクターの製造方法及びそのようにして得られるベクター |
WO2007020422A2 (fr) * | 2005-08-18 | 2007-02-22 | The University Of York | Recepteur |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2849044B1 (fr) * | 2002-12-24 | 2005-07-08 | Caption | Procede de fabrication d'un vecteur de molecules applicable dans le domaine du traitement de l'eau et vecteur obtenu |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2230593A1 (de) * | 1971-06-26 | 1972-12-28 | Kyowa Hakko Kogyo Kk | Verfahren zur Herstellung eines amphoteren Harzes |
WO1996015810A1 (fr) * | 1994-11-18 | 1996-05-30 | Michel Geffard | Conjugues monofonctionnels et/ou polyfonctionnels de la polylysine |
WO1996038493A1 (fr) * | 1995-05-30 | 1996-12-05 | The Regents Of The University Of California | Polymeres hydrosolubles et leurs compositions |
-
1998
- 1998-01-20 FR FR9800547A patent/FR2773808B1/fr not_active Expired - Fee Related
-
1999
- 1999-01-20 EP EP99900962A patent/EP1049736A1/fr not_active Withdrawn
- 1999-01-20 WO PCT/FR1999/000103 patent/WO1999036460A1/fr not_active Application Discontinuation
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2230593A1 (de) * | 1971-06-26 | 1972-12-28 | Kyowa Hakko Kogyo Kk | Verfahren zur Herstellung eines amphoteren Harzes |
WO1996015810A1 (fr) * | 1994-11-18 | 1996-05-30 | Michel Geffard | Conjugues monofonctionnels et/ou polyfonctionnels de la polylysine |
WO1996038493A1 (fr) * | 1995-05-30 | 1996-12-05 | The Regents Of The University Of California | Polymeres hydrosolubles et leurs compositions |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2006512435A (ja) * | 2002-12-24 | 2006-04-13 | ゲマック | 有効成分の拡散の分野において適用できる活性分子のベクターの製造方法及びそのようにして得られるベクター |
WO2007020422A2 (fr) * | 2005-08-18 | 2007-02-22 | The University Of York | Recepteur |
WO2007020422A3 (fr) * | 2005-08-18 | 2007-05-03 | Univ York | Recepteur |
Also Published As
Publication number | Publication date |
---|---|
FR2773808A1 (fr) | 1999-07-23 |
FR2773808B1 (fr) | 2000-05-05 |
EP1049736A1 (fr) | 2000-11-08 |
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