Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Reexamination Certificate
2000-10-17
2004-04-06
Wilson, James O. (Department: 1623)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
C435S018000
Reexamination Certificate
active
06716827
ABSTRACT:
TECHNICAL FIELD
The subject of the present invention is complexes formed by the inclusion of precursors, from a natural source, of organic isothiocyanates in cyclodextrins.
It particularly concerns the solubilisation and/or controlled release of bacteriostatic, bactericidal and/or fungicidal agents formed of organic isothiocyanates, from such complexes.
It also concerns bacteriostatic, bactericidal and/or fungicidal compositions containing such complexes, which can be used in the fields of food and food processing.
STATE OF PRIOR ART
Organic isothiocyantes are known to have remarkable bacterio- and fungistatic properties, and their activity in controlling the proliferation of aerobic and anaerobic micro-organisms has been well identified, as described in “Antimicrobial Properties of Isothiocyanates in Food Preservation” by P. J. Delaquis and G. Mazza, published by James Giese in “Food technology”, November 1995, pages 73 to 84 [1].
However, their physical properties (they are most often volatile liquids) make their use very difficult in food and food processing applications since it is impossible to control the minimal doses which ensure the preservation process without harming the organoleptic properties of the food to be preserved.
DISCLOSURE OF THE INVENTION
The precise subject of this present invention is bacteriostatic, bactericidal and/or fungicidal compositions in which the organic isothiocyanate is stabilised in the form of an inclusion complex in a cyclodextrin, permitting its solubilisation in an aqueous medium and control over its release.
According to the invention, the inclusion complex is formed of a natural precursor of an organic isothiocyanate included in a cyclodextrin.
According to the invention, the organic isothiocyanate preferably meets the formula:
R
1
—N═C═S (I)
in which R
1
represents an alkyl group, whether linear or branched, with 1 to 6 carbon atoms; an alkenyl group, linear or branched, with 2 to 6 carbon atoms; an arylalkyl group in which the alkyl group has 1 to 6 carbon atoms; a group having the formula:
in which q=1 or 2 and R
2
represents a hydrogen atom or an alkyl or alkoxyl group with 1 to 3 carbon atoms, the substituent R
2
being in ortho, para or meta position; a group with the formula R
3
CO(CH
2
)
n
— in which R
3
is an alkyl group with 1 to 3 carbon atoms and n is a whole number of 3 or 4; a group with the formula R
3
OCO(CH
2
)
n
— in which R
3
and n are as defined above; a methylthioalkyl group with the formula CH
3
S(CH
2
)
p
— in which p is a whole number from 1 to 10; or a group with the formula CH
3
—S—CH═CH—(CH
2
)
r
— in which r is a whole number from 1 to 8.
As an example of such isothiocyanates, mention may be made of those for which R
1
has the denotation given in the appended table.
The natural precursor of organic isothiocyanate, or glucosinolate, may meet the formula:
in which R
1
has the denotation given above.
These natural precursors may in particular be those mentioned in the appended table.
These natural precursors may be obtained from plant sources such as those also listed in the appended table.
The cyclodextrin used in the inclusion complex described above may be a natural cyclodextrin or a chemically modified cyclodextrin.
It is recalled that the cyclodextrins or cyclomaltooligosaccharides are compounds of natural origin, formed by the chain conformation of glucose units bonded at &agr;-1.4.
The natural cyclodextrins are &agr;-cyclodextrin which contains 6 glucose units, &bgr;-cyclodextrin which contains 7 glucose units and &ggr;-cyclodextrin which contains 8 glucose units. Much research work has shown that these cyclodextrins could form inclusion complexes with hydrophobic molecules, thereby permitting their solubilisation in aqueous media and their use in various industries, as described in the work entitled: “Cyclodextrins and their Industrial Uses” by D. Duchêne published by Editions de Santé, 1987, pages 299 to 326, [2].
According to the invention, not only a natural cyclodextrin may be used, but also a natural cyclodextrin that is chemically modified through the addition of appropriate substituents. Said modified cyclodextrin may meet the formula:
in which m=6, 7 or 8 and the R
4
s which may be identical or different, represent OH or a group chosen from among the X-alkylated or X-arylated groups in which X represents a carbon atom or a heteroatom provided that at least one of the R
4
s is not OH.
In this case, the substituents R
4
of cyclodextrin are chosen such as to improve its properties, in particular in respect of the solubilisation and stabilisation of the organic isothiocyanates.
According to the invention, the inclusion complex of a natural precursor of an organic isothiocycate in a cyclodextrin, using an aqueous solution of cyclodextrin, may be prepared by the addition of the natural precursor to this solution. The cyclodextrins used are those previously described.
In this manner, the inclusion complex may be formed either in the form of an aqueous solution, or in the form of a precipitate which is subsequently separated from the solution. In this latter case, an aqueous solution saturated with cyclodextrin may be used.
According to the invention, the inclusion complexes of natural precursors of organic isothiocyanates in cyclodextrins may be used to prepare an inclusion complex of an organic isothyanate in a cyclodextrin.
Indeed, it is known that these natural precursors of organic isothiocyanates may be converted into the corresponding isothiocyanates by hydrolytic reaction with myrosinase in accordance with the following reaction diagram:
Myrosinase is an enzyme naturally present in Cruciferae. The enzymatic hydrolysis of the natural precursor of formula (IV) by myrosinase leads to the corresponding organic isothiocyanate and to the release of a molecule of D-glucose and potassium acid sulphate.
According to the invention, it has been discovered that it is possible to prepare an inclusion complex containing organic isothiocyanate from an inclusion complex containing the natural precursor of this isothiocyanate through the action of myrosinase on this complex.
Therefore, a further object of this invention is a method for preparing an inclusion complex formed of an organic isothiocyanate included in a cyclodextrin, which comprises the following steps:
a) preparing, in an aqueous solution, an inclusion complex containing a natural precursor of an organic isothiocyanate in cyclodextrin, and
b) submitting the complex so obtained to the action of myrosinase in aqueous solution to convert the natural precursor included in the cyclodextrin into the corresponding organic isothiocyanate.
In this case, the aqueous solution used in the second step, and optionally in the first step, is a solution suitable for hydrolysis by myrosinase. It may be a buffer solution such as a phosphate buffer solution with a pH value of 6.
A further object of the invention is a bacteriostatic, bactericidal and/or fungicidal composition, made up of a dry mixture containing:
a) an inclusion complex of a natural precursor of an organic isothiocyanate, having bactericidal, bacteriostatic and/or fungicidial properties, in a cyclodextrin, and
b) myrosinase.
By way of example, the composition may be in powder, granule, wettable powder form etc. This composition may comprise appropriate vehicles and additives such as those generally used for the production of bacteriostatic, bactericidal and/or fungicidal products intended for the food or food processing industries.
It may be prepared using conventional methods.
With this composition, at the time of use, when the dry mixture is placed in contact with water or a humid atmosphere, the presence of water will convert the natural precursor present in the inclusion complex into the corresponding organic isothiocyanate through enzymatic hydrolysis with the myrosinase in the composition.
In this case, the composition is for example in powder form, or wettable powder form.
REFERENCES:
patent: 4528271 (1985-07-01), Pechany
Perly Bruno
Rollin Patrick
Roselli Cécile
Commissariat a l'Energie Atomique
White Everett
Wilson James O.
LandOfFree
Complexes for immobilizing isothiocyanate natural precursors... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Complexes for immobilizing isothiocyanate natural precursors..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Complexes for immobilizing isothiocyanate natural precursors... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3198024