Note: Descriptions are shown in the official language in which they were submitted.
33
This invention relates to sweeteners for in~3estible
products, oral compositions and sweetening compositions.
By an "ingestible product" there is meant one which
in the ordinary course of use is intended to be swallowed,
for instance a foodstuff or beverage, or an orally administered
pharmaceutical composition. ~y an "oral composition" there is
meant one which in the ordinary course of use is not intended
to be ingested as such, but is taken into the mouth for the
treatment of the throat or buccal cavity, for instance a tooth-
paste, tooth powder, mouth wash, gargle, troche, dental lotionor cnewing gum~ By a "sweetening composition" there is meant
a composition which is not itself taken orally, either to be
ingested or held in the mouth, but instead is intended to be
added to other ingestible products or oral compositions to
render them sweet or to increase their sweetness.
Although sucrose is still the most widely used sweet-
ening agent, many efforts have been made to find substantially
sweeter alternatives which could be used when it is desired -to
combine a high degree of sweetness with a low calorie content
and/or a low risk of dental caries, for example in dietetic
products and in the manufacture of soft drinks. The two most
successful non--sucrose sweeteners (that is to say sweeteners
comprising a compound other than sucrose itself) to date have
been saccharin and cyclamate, having respectively about 200 and
about 30 times the sweetening power of sucrose, but the use of
these sweeteners, particularly cyc]amate, has recently been
restricted or banned in some countries because of doubts about
their safety. Saccharin also suffers from the disadvantage of
an unpleasantlybitter after-taste which can be detected by many
people.
More recently, many other non-sucrose sweetcners have
been investigated, some of natural origin and others synthetic,
- 1 -
33
covering a wide range of chemical structures. These compounds
have included proteins, such as monellin, thaumatin and miraculin,
dipeptides such as aspartame, and dihydrochalcones such as neo-
hesperidin dihydrochalcone. Ilowever, apart from the difficulties
of synthesizing or extracting such sweeteners, they do not nec-
essarily possess the same quality of sweetness as sucrose: in
particular, as compared with sucrose, the sweetness may be slow
in onset and relatively lingering, and there may be a li~uorice-
like or other after-taste, making the sweetener unsuitable as a
d.ireet replacement for sucrose unless these differences can be
mas~ed.
Although numerous sweeteners of widely diverse chemical
structures have now been investigated, it is significant to note
that sweetness substantially greater than that of sucrose has
not been discovered in any derivative of suerose or in any other
ear~onydrate: when an intensely sweet substance has been dis-
eovered, sueh as saceharin, cyclamate and the other non-suerose
sweeteners already mentioned, its structure has always been
radieally different from that of sucrose. Indeed, it is known
that the presenee of some substituents on the suerose molecule
ean, in faet, destroy its sweetness and even impart a bitter
t.aste.
Most surprisinglyj and in complete contrast to previous
knowledge about non-suerose sweeteners, we have now discovered
that eertain derivatives of sucrose and of a sucrose isomer are
very mueh sweeter than suerose itself, their sweetness being
eomparable in intensity with that of saeeharin, but having a
quality similar to that of sucrose.
Aeeording to the present invention we provide as
sweetening agents compounds selected from the group consisting
of 4--ehloro-4-deoxy-~-D-galactopyranosyl-~-D--fructofuranoside;
4-cllloro-4-deoxy-~-D-galactopyranoSyl-1, 6--dichloro-1, 6-dideoxy-
233
~-D-fructofuranoside; 4,6--dichloro-4~ 6-dideoxy~ D-galacto-
pyranosyl-6-chloro-6~deoxy~ D fructofuranoside and 6,1',
6'-trichloro-6, 1', 6'-trideoxy-sucrose.
The compounds can be used as sweetening agents in any
conventional way, including the sweetening of "ingestible pro-
ducts" (as previously defined), for example foodstuffs, bev-
erages and orallyadministered pharmaceutical compositions, and
of "oral compositions" (as previously defined), for example
toothpastes, chewing gums and mouth washes. They can also be
used, with conventional liquid or solid extenders and carriers,
in "sweetening compositions" (as previously defined).
The extender or carrier comprises any suitable vehicle
for the sucrose derivative so that it can be formulated in a
composition which can conveniently be used for sweetening other
products, for example granules, tablets or drops. The extender
or carrier may thus include, for example, conventional water-
dispersible tabletting ingredients, such as starch, lactose and
sucrose itself; low--density bulking agents to provide a granular
sweetening composition having a volume per unit sweetness
equivalent to that of sucrose, for example, spray dried malto-
dextrins- and aqueous solutions containing adjuvants such as
stabilising agents, colouring agents and viscosity-adjusting
agents.
Beverages, such as soft drinks, containing one of the
said sucrose derivatives may be formulated either as sugar-
free dietetic products, or "sugar-reduced" products containing
the minimum amount of sugar required by law. In the absence of
sugar lt is desirable to add further agents to provide a "mouth-
feel" similar to that provided by sugar, for example, pectin or
a vegetable gum. For example, pectin may be added at a level of
from 0.1 to 0.15~ in a bottling syrup.
The compounds which may be used according to -t~le present
- 3 -
23;~
invention are shown in the following Table. The compounds are
represented by the formula: -
R~ R~
R ~--~ \ ~Rl o
~ >~ ~/6
1~0 ~1 o / ~
OH
.
Compound No. ~1 ~ R R ~ ~PPrtXlrnS(X Sucrose)*
I . l
1 OH H C1 OH OH 5
2 Cl H Cl OH Cl 2000
3, ~H H Cl Cl Cl 4
Cl OH H Cl Cl l00
. .. .
*Sweetness Evaluation
The sweetness is evaluated in aqueous solution, bycomparison with a 10% by weight aqueous solution of sucrose.
The results were obtained from a small taste panel and are,
tl~erefore, not statistically accurate, but indicate the approx-
imate order of sweetness.
The cor,lpounas in Table 1 are as follows (the sys-terriatic
nomenclature is given first, followed br a trivial n.-,me base~ on
"galacto sucrose" in chose cases where a 4--cliloro substituent
is p L~resent):
1. 4-chloro-4-deox~ -D--c~alacto,oyranosyl--~-D-
~'
233
fructofuranoside (i.e. 4-chloro-4-deoxygalactosucrose)
2. 4-chloro-4-deoxy-~-D-galactopyrallosyl-1, 6-dicnloro-
1, ~-di~eoxy-~-D-fructofuranoside (i.e. 4-1', 6'-trichloro-4,
1', 6'-trideoxygalacto sucrose)
3. 4,6-dichloro-4, 6-dideoxy-~-D--galactopyranosyl-6-
chloro-6-deoxy~ D-fructofuranoside (i.e. 4,6,6'-trichloro-4,
6,6'-trideoxygalactosucrose)
4. 6,1',6'-trichloro-6, 1',6'-trideoxysucrose
The remarkable sweetness of the compounds is combined
with an LDSo (lethal dose 50%) which, in the case of compound 2
in Table 1, for example, is in excess of 16g/kg in mice, that
being the largest dose which can be administered in practice.
The compounds are all ~nown and can be-prepared by the
synthetic routes disclosed in the chemical literature. However,
none of the compounds has previously been recognised as possessing
any useful sweetness.
The compound 2 is reported in Carbohyd. Res., 40(1975),
285; Compound 3 in Carbohyd. ~es., 44, (1375), 37; and Com~ound 4
in Carbohyd. Res., 25, (197~), 504 and ibid 44, (1975), 12-13.
Com~ound 1 is reported in Carbohyd, Res., 40, (1975), 285-298.
All the compounds may be prepared by reaction of a
sucrose ester, having free hydroxy groups in the portions re-
uired to ~e c}llorinated, with sulphuryl chloride to o~tain the
corresponding chlorosulphate derivative. This, on treatment with
a source of chloride ions such as lithium chloride, in amide
solvent such as hexametllyl pihosplloric triamide, yields the
cillorinated sucrose ester. Hydrolysis of the chloro-ester,
e.g. using sodium methoxide in dry methanol, then liberates the
free chlorosucrose. The reaction with sulphuryl chloride is con-
~7eniently effected at a reduced temperature in an inert solvent
in the presence of a base, for example chloroEorm containing
pyridine.
- 5 -
33
A similar metilod can ~e used for furtller chlorinating
an already clllorinated sucrose derivative.
Tne following ~xamples illustrate the invention further
(tcmperatures are given in degrees centigrade).
EXAMPLE 1
Sweetening tablets for beverages, etc.
Each ta~let contains:
Compound 2 2 mg
together Witil a dispersable tablet base (ca. 60 mg) containing
sucrose, gum arabic and magnesium stearate, and is equivalent in
sweetness to about 4.5 g sucrose.
EXAMPLE 2
Bulked sweetener
A bulked sweetener having the same sweetness as an equivalent
volume of sucrose (granulated sugar) is prepared by mixing the
following ingredients and spray-~drying to a bulk density of
0.2 g/cc:
maltodextrin solution containing dry weight 222.2 g
Compound 2 0.5 g
The resulting composition has a sweetening po~er equivalent to
approximately 2 kilograms of sugar.
EXAMPLE 3
Reduced calorie cola drink containing sugar
Ingredients to prepare 100 ml bottling syrup:
Compound 2 20 mg
Sugar 60 mg
Benzoic acid 35 mg
Pllosphoric acid (conc.)1 ml
Cola flavour 1.1 ml
Colour ad lib.
Make up to 100 ml with mineral water.
This syrup may then be added in 25 ml doses to carbonated 225
ml aliquots of chilled mineral water.
- 6 -
33
EXA_PLE 4
Carbonated low calorie lemonade (sugar~free)
. _ . . . _ .
Ingredients to prepare 100 ml syrup:
Compound 2 19 mg
Benzoic acid 35 mg
Citric acid (dry base) 1.67 g
Lemon essence 0.8 g
Make up to 100 ml in mineral water.
Tl~is syrup can be added in 25 ml doses to 225 ml aliquots of
carbonated cnilled mineral water.
EXAMPLE 5
Tootllpaste
_ _
% by weight
Dibasic calcium phospilate 50%
Clycerol 20%
Sodium lauryl sulphate 2.5%
Spearmint oil 2.5%
Gum tragacanth 1.0%
Compound 2 0.008%
Water 23.992%
The ingredients are mixed to produce a sl~earmint ~lavoured tooth-
paste of accepta~le sweetness but free from sugar or saccharin.
EXAMPLFJ 6
part by weight
Polyvinyl acetate 20
Butyl plltllalylbutylglycolate 3
Polyisobutylene 3
Microcrystalline wax 2
3~ Calcium carbonate 2
Flavouring/aroma
Compound 2 0.17
~'
6233
Glucose 10
The above chewing gum base can be cut into conventional tablets
or stri~s.
~1
