Stabilized sucralose complex

The chlorosucrose sweetener known as sucralose is prepared in a thermally stable composition by co-crystallization with a cyclodextrin. The resulting crystalline product may be comminuted to form particles of desired size for use as a sweetener component in place of or in addition to known sweeteners such as sucrose, saccharin and the like, in a variety of foods, comestibles, and oral medications. The preparation of the stabilized sucralose compositions of the present invention constitutes a molecular encapsulation of the sucralose within the cyclodextrin thereby protecting the sucralose from discoloration caused by heat. Numerous applications for this stabilized complex are suggested and disclosed.

BACKGROUND OF THE INVENTION 
The present invention relates to the preparation of chlorosucrose 
sweeteners and particularly to the preparation of such sweeteners in a 
stable form useful for incorporation in a variety of food and 
confectionery products as well as for medicinal uses. 
The sweetening agent known as sucralose comprises a chlorosucrose sweetener 
derived from a class of compounds based upon sucrose and galactosucrose in 
which one or more hydroxy groups are replaced by chlorine atoms, and is 
described in U.K. Patent No. 1,543,167, the disclosure of which is 
incorporated herein by reference. Of particular interest is the compound 
sucralose, (4-chloro-4-deoxy-.alpha.-D-galactopyranosyl 
1,6-dichloro1,6-dideoxy-.beta.-D-fructofuranoside, also known as 
4,1',6',-trichloro-4,1',6'-trideoxygalactosucrose). Sucralose and the 
other members of its chemical family have been identified as intensely 
sweet, offering a sweetness several hundred times that of sucrose, and are 
of particular interest for use as low calorie sweeteners to replace 
saccharin in various products, including foods, candy, comestibles, 
beverages and orally received medicinals such as cough drops. 
This class of compounds is generally relatively stable and inert and 
particularly exhibits the stability in acid aqueous solutions, in marked 
contrast to peptide-based sweeteners such as aspartame. Under completely 
dry conditions, however, sucralose which is present in a crystalline form 
tends to discolor in response to elevated temperatures. For example, such 
discoloration can be exhibited after twenty minutes of exposure of pure 
dry sucralose to a temperature of 100C., wherein the color changes to a 
pale brown. 
Efforts have previously been undertaken to stabilize sucralose by various 
techniques. For example, in U.K. Patent Application No. 2,169,601A to 
Jackson, sucralose is treated by co-crystallization with a nitrogenous 
base and in particular compounds containing an amine group such as 
niacinamide or an amino acid. An alternative approach was pursued by 
Jackson and Jenner and disclosed in European Patent Publication No. 
0,255,260, wherein crystalline sucralose was prepared and then reduced to 
particles of critical dimension, in particular such particles no greater 
than 10 microns in mean particle size with a maximum particle size no 
greater than twice the mean. 
Neither of the foregoing approaches has been totally satisfactory as the 
resulting sucralose products have continued to exhibit commercially 
undesirable thermal instability, and in the instance of the 
co-crystallization with the nitrogenous base material are further 
qualified in their acceptability by the admixture with a material that may 
be of reduced sweetness sensation. 
A need therefore exists to develop a truly thermally stable form of 
sucralose that likewise maximizes the delivery of the sweetness sensation 
when such material is incorporated into foods and related comestible 
products. 
SUMMARY OF THE INVENTION 
In accordance with the present invention, a thermally stabilized 
composition is prepared which comprises a co-crystallized complex of 
sucralose and a cyclodextrin, preferably .beta.(.beta.CD). The 
co-crystallized complex comprises at least about 5% by weight of 
cyclodextrin and is prepared in particulate form to a uniform particle 
size. In a preferred embodiment, the co-crystallized complex comprises at 
least about 15% by weight of the cyclodextrin. 
The complex may be prepared by dissolving a mixture of cyclodextrin and 
sucralose in a non-aqueous solvent such as methanol, followed by the 
removal of the methanol and the placement of the remaining slurry in a 
solvent such as ethyl acetate, filtering out the formed precipitate, 
washing the same with a further quantity of ethyl acetate and then drying 
the resulting crystals. Thereafter, the crystals may be ground down to the 
desired particle size and are ready for use. 
The resulting crystalline complex exhibits extended thermal stability and 
can be incorporated into a variety of food, confectionery and medicinal 
products where sweeteners such as saccharin may be desirable. Accordingly, 
the present invention extends to such products having the complex included 
therein as an ingredient, such as anti-bacterial oral preparations and the 
like. 
Accordingly, it is a principal object of the present invention to prepare a 
thermally stable form of the sweetener sucralose. 
It is a still further object of the present invention to prepare the 
sweetener sucralose as aforesaid which exhibits extended thermal stability 
in conjunction with sweetness delivery comparable to that of the 
unmodified sweetener material. 
It is a still further object of the present invention to provide a method 
for the preparation of a thermally stable complex of the sweetener 
sucralose which is simple and economical to perform. 
It is a still further object of the present invention to prepare one or 
more comestible products containing a thermally stabilized complex 
including the sweetener sucralose. 
It is a still further object of the present invention to prepare one or 
more food products containing a thermally stabilized complex of the 
sweetener sucralose. 
It is a still further object of the present invention to prepare one or 
more medicinal products containing a thermally stabilized complex of the 
sweetener sucralose. 
Other objects and advantages will become apparent to those skilled in the 
art from a review of the ensuring detailed description which proceeds with 
reference to the following illustrative drawings.

EXAMPLE I 
Several stabilized sucralose compositions were prepared by the following 
procedure. A quantity of .beta.was added to sucralose and the resulting 
mixture was then dissolved in 25 ml. methanol and thereafter heated to 
40.C. with the application of vacuum suction to draw off the methanol. 
After 1 hour the remaining slurry was dissolved in ethyl acetate and the 
resulting solution was heated to complete the formation of the solution. 
The solution was then cooled to 20.C. and allowed to crystallize overnight 
in a refrigerator. The crystalline precipitate was then filtered off by 
cold-filtration, and thereafter air-dried and then milled to a uniform 
particle size. 
A series of samples of co-crystalline complexes were prepared for testing, 
and accordingly 0.25, 0.5 and 1.0 g of cyclodextrin were added to 
sucralose to prepare a total of 5 g of mixture. The samples thus 
corresponded to mixtures containing 5%, 10% and 20% cyclodextrin. As a 
comparison, a sample containing pure sucralose was prepared in the same 
manner, and was likewise milled identically to eliminate any particle size 
differences. 
The powders thus prepared were subjected to a temperature of about 195 F 
(92.C.) and were monitored during heating to note the length of time that 
it took for the respective samples to turn light brown and to thereby 
discolor. The results are set forth in Table 1, below. 
TABLE 1 
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ELAPSED TIME 
SAMPLE BEFORE DISCOLORATION 
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SUCRALOSE ALONE 60 Minutes 
SUCRALOSE-5% 80 Minutes 
CYCLODEXTRIN 
SUCRALOSE-10% 90 Minutes 
CYCLODEXTRIN 
SUCRALOSE-20% 180 Minutes 
CYCLODEXTRIN 
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Referring to Table 1, it is apparent that a 33.3% improvement in thermal 
stability as reflected in resistance to discoloration is achieved by the 
co-crystallization of sucralose with as little as 5% cyclodextrin, with a 
50% improvement results from the use of 10% cyclodextrin. The most 
dramatic improvement of 300% was seen when co-crystallization was 
conducted with 20% by weight of cyclodextrin. A complex containing only 1% 
cyclodextrin was also prepared and tested, and although the data was not 
presented above, it indicated that such a minimal concentration of 
cyclodextrin was largely ineffective. 
Lastly, it was noted that the measurements and results presented herein 
were more apparent when the tests were conducted at the lower temperature 
range selected. 
EXAMPLE II 
Additional thermal stability testing was conducted between a free sucralose 
control and inventive samples containing 2%, 3%, 5%, 10% and 15% 
cyclodextrin, respectively, for the purpose of confirming the results of 
the tests conducted in Example 1, and to determine the activity and 
effectiveness of inventive complexes prepared with other variant 
cyclodextrin contents. The preparation of the control and inventive 
samples was the same as that employed with the samples of Example 1. The 
temperature applied during the stability test was 195.degree. F..+-.5.F. 
The results are set forth in Table 2 below, as well as in FIG. 1, which 
represents a plot of time delay in discoloration of the inventive samples 
over the control sample of pure sucralose. 
TABLE 2 
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MINUTES 
ELAPSED TIME DELAYED VS. 
BEFORE FREE 
SAMPLE DISCOLORATION SUCRALOSE 
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SUCRALOSE 65 Minutes 0 
ALONE 
SUCRALOSE-2% 
69 Minutes 4 
CYCLODEXTRIN 
SUCRALOSE-3% 
72 Minutes 7 
CYCLODEXTRIN 
SUCRALOSE-5% 
82 Minutes 17 
CYCLODEXTRIN 
SUCRALOSE-10% 
94 Minutes 29 
CYCLODEXTRIN 
SUCRALOSE-15% 
136 Minutes 71 
CYCLODEXTRIN 
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The data presented above and in FIG. 1 further confirm the threshold of 
significant thermal stability exhibited by the use of 5% cyclodextrin, and 
also demonstrates a substantial improvement in stability as the level of 
cyclodextrin is increased from 10% to 15%. 
EXAMPLE III 
In this Example, a comparison was made between complexes of the present 
invention that differed as to the quantity of cyclodextrin present, to 
determine whether the presence of cyclodextrin has any effect on the 
sweetness intensity and delivery of the sucralose component. Accordingly, 
0.29 g of a complex containing 5% cyclodextrin and 0.31 g of a complex 
containing 10% cyclodextrin were separately dissolved in 100 g of water to 
form equivalent solutions of 0.28% sucralose content. A solution 
containing 0.28% of free sucralose was also prepared and tested. 
Equal samples of each of the solutions were given to an expert panel. The 
panel concluded that all of the solutions were sweet and noted no 
differences among the respective solutions. From the above results, it can 
be concluded that cyclodextrin in these amounts does not diminish the 
sweetness delivery and sensation offered by sucralose. 
EXAMPLE IV 
The sweetness intensity of the invention in a gum formulation was compared 
herein with that of free sucralose, a co-crystalline complex of sucralose 
and niacinamide, the latter prepared in accordance with the procedures 
taught in the United Kingdom Application No. 2,169,601A to Jackson, 
disclosed earlier herein. Specifically, samples of the inventive complex 
containing 5% cyclodextrin, free sucralose and the complex of Jackson 
publication prepared with 3% by weight of niacinamide, were respectively 
formulated and incorporated into otherwise identical spearmint flavored 
chewing gums in equal amounts and by equally identical procedures. After 
formulation, the gum samples were subjected to expert chew panel 
evaluation of sweetness intensity. 
Accordingly, the gum samples were given to a panel of scientists, all of 
whom chew on a regular basis for the purpose of screening the samples. 
During the experiment each panelist was asked to evaluate the sweetness 
intensity of each of the samples and to render an opinion based on the 
following numerical values. 
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0 10 20 30 40 50 60 70 80 90 100 
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LOWEST HIGHEST 
SWEETNESS SWEETNESS 
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The panelists were asked to rate the samples at intervals of 30 seconds, 2 
minutes and 6 minutes. The results of the ratings assigned by each of the 
panelists to each of the samples were averaged together and then compared. 
The data are expressed in graphical form in FIG. 2. 
As can be seen from FIG. 2, the sample containing the inventive sucralose 
complex was rated better as to sweetness than both of the other samples. 
Accordingly, the present complex offered an initial sweetness that was 
greater than free sucralose. By comparison, the sample prepared in 
accordance with the Jackson disclosure offered the lowest initial 
sweetness intensity. 
This invention may be embodied in other forms or carried out in other ways 
without departing from the spirit or essential characteristics thereof. 
The present disclosure is therefore to be considered as in all respects 
illustrative and not restrictive, the scope of the invention being 
indicated by the appended claims, and all changes which come within the 
meaning and range of equivalency are intended to be embraced therein.