Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2000-03-24
2003-04-08
Wilson, James O. (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C424S652000, C536S103000
Reexamination Certificate
active
06544964
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a process for the fixation or separation of ions, particularly of Pb, by per(3,6-anhydro)cylcodextrin derivatives.
PRIOR ART
Cyclodextrins or cyclomaltooligosaccharides are compounds having a natural origin formed by the linking of glucose units which are &agr;(1,4)-bonded.
Numerous works have revealed that these compounds could form inclusion complexes with hydrophobic molecules, thus permitting their solubilization in aqueous media. Numerous applications have been proposed for taking advantage of this phenomenon, particularly in the pharmaceutical field, as is described by D. Duchêne “Pharmaceutical application of cyclodextrins” in “Cyclodextrins and their industrial uses”, D. Duchêne, Editions de Santé, Paris, 1987, pp 213-257.
Pharmaceuticals have already been marketed in Japan, Italy and more recently in France, in the form of complexes in cyclodextrins. In France, the first active principle marketed in the form of an inclusion complex in a cyclodextrin is piroxicam, which is an anti-inflammatory agent marketed by Pierre Fabre Medicament under the name BREXIN
(R)
. Among the very numerous modified derivatives of said cyclodextrins, those for which the cavity is turned on itself have interesting properties, even though their capacity to include organic molecules is lost or very limited. Compounds of this type are per(3,6-anhydro)cyclodextrins.
The synthesis of said peranhydrocyclodextrins has been described as from 1991 in document 1: Gadelle A. and Defaye J., Angew. Chem. Int. Ed. Engl., 1991, 30, 78-79; and document 2: Ashton P. R., Ellwood P., Staton I. and Stoddart J. F., Angew. Chem. Int. Ed. Engl., 1991, 30, 80-81) and it has been demonstrated that these derivatives have interesting solubilities both in water and organic solvents. Several subsequent studies (document 3: Yamamura H. and Fujita K. Chem. Pharm. Bull., 1991, 39, 2505-2508; document 4: Yamamura H., Ezuka T., Kawase Y., Kawai M., Butsugan Y. and Fujita K., J. Chem. Soc., Chem. Com., 1993, 636-637; and document 5: Yamamura H., Nagaoka H., Kawai M. and Butsugan Y., Tetrahedron Lett. 1995, 36, 1093-1094) have also demonstrated that these peranhydro derivatives could complex alkaline ions with a non-negligible selectivity.
Ashton et al in J. Org. Chem., 60, 1995, pp 3898-3903, have described the synthesis of the pernanhydro-&bgr;-cyclodextrin derivative substituted in the 2-position by a methyl group.
However, this chemical modification has not been carried out with a view to optimizing the complexing or selectivity properties of the peranhydrocyclodextrins.
DESCRIPTION OF THE INVENTION
The present invention relates to the use for the separation or fixation of ions of derivatives of peranhydrocyclodextrins in which a chemical modification has been carried out for modifying their properties, particularly their selectivity with respect to the ions which they are liable to complex and in particular with respect to lead.
According to the invention, this modification relates to the hydroxyl groups present on said molecule, as well as the configuration of carbon C
2
, which can be reversed for leading to L-mannose-type derivatives.
Thus, the invention relates to a process for the fixation or separation ions, which consists of contacting a medium containing said ions with a derivative of per(3,6-anhydro)cyclodextrin, complying with one of the following formulas:
in which at least one of the R
1
represents the methoxy group and the other R
1
, which can be the same or different, represent a group complying with one of the formulas: OH, OR
2
, SH, SR
2
, OCOR
2
, NH
2
, NR
2
R
3
, CONR
2
R
3
, CONH
2
, CN, COOR
2
, COOH and R
2
, in which R
2
represents a saturated or unsaturated, aliphatic or aromatic, hydrocarbon group, which can have one or more heteroatoms chosen from among O, S and N, and R
3
represents a hydrogen atom or a saturated or unsaturated, aromatic or aliphatic, hydrocarbon group, which can have one or more heteroatoms chosen from among O, S and N, and n is equal to 6, 7 or 8, for fixing said ions in complex form with the per(3,6-anhydro)cyclodextrin derivative and for separating them from said medium.
In the cyclodextrin derivative of formula (I) or (II), the aliphatic or aromatic, hydrocarbon groups which can be used for R
2
and R
3
can be of various types. They are constituted by a carbon chain, in which certain carbon atoms can be replaced by one or more heteroatoms such as O, S and N and can have one or more ethylene or acetylene unsaturations. Moreover, the hydrocarbon group can have different substituents, in particular functional groups or halogen atoms. The aromatic hydrocarbon groups can be constituted by the optionally substituted tosyl group and phenyl group, e.g. by alkyl groups having 1 to 20 carbon atoms. R
2
and R
3
can in particular represent a straight or branched, alkyl group having 1 to 20 carbon atoms.
According to a preferred embodiment of the invention, intended more particularly for the separation of lead ions, the per(3,6-anhydro)cyclodextrin derivative is an &bgr;-cyclodextrin derivative, i.e. in the aforementioned formulas (I) and (II), n is equal to 6.
Preferably, the derivative used complies with formula (I), in which all the R
1
represent the methoxy group and n is equal to 6.
The ions which can be fixed or separated by the process according to the invention can be of various types. They can e.g. be ions of alkali metals, actinides, lanthanides or polluting metals such as lead, mercury, cobalt and strontium.
The process according to the invention more particularly applies to the separation and fixation of lead in complex form.
Thus, lead and its derivatives pollute the environment and are toxic both to man and animal. The main toxic effects affect the neurological development and the functioning of the nervous system. It is consequently necessary to separate and eliminate lead from the environment and store it safely.
In addition, products which would make it possible to ensure the lead decontamination of living beings by preventing the action of lead on the nervous system and on other organs, would be of great interest for solving these problems.
According to the invention, it has been found that derivatives of per(3,6-anhydro)cyclodextrins complying with the above formulas (I) and (II), have a high specificity for lead and are capable of complexing it with high yields able to reach 100%, even in the presence of other ions, such as sodium ions.
Thus, it is possible to separate the lead from the surrounding medium in complex form.
The invention also relates to complexes of lead and derivatives of per(3,6-anhydro)cyclodextrins of formulas (I) or (II) described hereinbefore.
For implementing the process according to the invention, it is possible to use the per(3,6-anhydro)cyclodextrin derivative of formula (I) or (II) in the form of an aqueous solution or organic solution.
When the medium containing the ions to be separated or fixed is an aqueous solution, it is possible to dissolve the cyclodextrin derivative in an organic solvent which is immiscible with the aqueous solution, e.g. in chloroform, in order to form the complex in the organic solution and separate it easily from the aqueous solution.
It is also possible to use the cyclodextrin derivative in aqueous solution, particularly for the lead decontamination of living beings.
Thus, it is known that cyclodextrin derivatives of formulas (I) or (II) are biocompatible compounds. They can consequently be administered to man or animals for ensuring the fixation of the lead in complex form and thus prevent its interaction with the organs of the human or animal body.
The invention also relates to a pharmaceutical composition for the lead decontamination of a living being, characterized in that it comprises a per(3,6-anhydro)cyclodextrin derivative complying with one of the following formulas:
in which at least one of the R
1
represents the methoxy group and the other R
1
, which can be the same or different, represent a group complying with one of the formulas: OH, OR
Baudin Cecile
Debouzy Jean-Claude
Fauvelle Florence
Gadelle Andree
Perly Bruno
Burns Doane , Swecker, Mathis LLP
Commissariat A L'Energie Atomique
Maier Leigh C.
Wilson James O.
LandOfFree
Method for fixing or separating ions, in particular of lead,... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for fixing or separating ions, in particular of lead,..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for fixing or separating ions, in particular of lead,... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3034480