The invention relates to the effect of oligosaccharides on intestinal transit
in mammals.
The term "intestinal transit" is intended to mean the complex operation
performed by the intestines in order to transport the food bolus from the stomach
to the rectum.
Currently, an increasing number of human beings are suffering from health
problems linked to intestinal transit dysregulation. Intestinal transit dysregulation
can result both in transit times which are too long (hypotransit) and transit times
which are too short (hypertransit).
Health problems resulting from intestinal transit dysregulation can vary
from simple intestinal bloating to acute pain (hypotransit). In the case of
intestinal transit which is too rapid, dehydration may even occur. In certain
regions of the world it is a major public health problem, which especially
involves children and is one of the most common causes of infant mortality.
In the most developed regions of the world, intestinal transit dysregulation
is worsened by a sedentary lifestyle, food which is too low in fibre and by stress.
The effect of certain oligosaccharides on intestinal transit is known.
Galactofructose is in fact commonly used to accelerate intestinal transit.
However, this can result in the conversion of intestinal hypotransit into intestinal
hypertransit ("laxative" effect).
FR 2 891 439 describes a food supplement comprising an agent for
increasing the weight of faeces and a laxative. The laxative is preferably in
particular lactulose. However, the food supplement in FR 2 891 439 is intended
for patients suffering from constipation, or even from advanced stages of
constipation.
The invention aims to improve the well-being of generally healthy
mammals, through acting on their intestinal flora.
Consequently, the invention relates to galactofructose for its regulatory
effect on the intestinal transit time of mammals, when it is incorporated into a
food composition and when said composition is absorbed by the mammal in an
amount corresponding to daily doses of galactofructose, averaged over 30
consecutive days, of between 0.1 and 5 g, advantageously between 0.1 and 2 g.
3
As those skilled in the art will easily understand, the term "to average"
should be understood here in its mathematical sense, and therefore means "to
calculate the average" (ref.: http://en.wiktionary.org/wiki/moyenner). Just as
obviously, the average to be calculated in order to define the dosage in
accordance with the invention is the arithmetic average of the daily doses
absorbed during the period of 30 days.
In the invention, the mammal is preferably healthy, showing no sign of
disease.
Galactofructose, also called lactulose, is a disaccharide formed from the
combination of two monosaccharide molecules, fructose and galactose. Its
chemical formula is (4-O-β-D-Galactopyranosyl-β-D-fructofuranose). It is an
isomerization product of lactose, which both have the same empirical formula
(C12H22O11) and molecular weight (342.3).
Galactofructose, when it is absorbed in small amounts according to the
invention in food compositions, improves the well-being of mammals. The
invention also has the advantage of not interfering with the taste and the
appearance (for example colour) of the food compositions. This is particularly
advantageous for feeding infants and animals, in which a taste modification can
cause the foodstuff to be rejected.
It is recommended that the galactofructose according to the invention
comprise less than 30%, preferably less than 25% by total weight of sugars such
as fructose, epilactose, galactose or lactose relative to the amount of
galactofructose.
The galactofructose according to the invention is incorporated into a food
composition. The expression "food composition" is understood to mean a
composition intended for feeding mammals. The mammals are preferably human
beings, although the invention can also be used for improving the well-being of
various mammalian animals, such as domestic animals. The food composition is
advantageously a composition absorbed regularly, preferably at least once a
month, more preferentially once a week, and particularly preferentially daily.
Food compositions for human beings, such as bread, butter, milk, fermented
dairy products, cereals, biscuits, beverages and fruit juices are advantageous.
In one particularly preferred embodiment of the invention, the food
compositions are intended for feeding children.
According to the invention, the galactofructose is absorbed in daily
amounts, averaged over 30 consecutive days, of between 0.1 and 5 g,
4
advantageously between 0.1 and 2 g. This means that the daily doses may vary
but that the total dose absorbed over one month divided by 30 is between 0.1 and
5 g, advantageously between 0.1 and 2 g.
In another embodiment of the invention, the amounts are averaged over 7
days, which means that the total dose absorbed over seven consecutive days
divided by 7 is between 0.1 and 5 g, advantageously between 0.1 and 2 g.
In one advantageous embodiment of the invention, the daily dose absorbed,
not averaged, exceeds 0.1 g, preferably 0.5 g. It is recommended, furthermore,
that it remain less than 5 g and in certain cases less than 2 g.
In one preferred variant, the daily doses of galactofructose are between 0.1
and 5g, advantageously between 0.5 and 2 g, for at least 30 consecutive days. In
this variant, galactofructose is absorbed regularly every day and the doses are no
longer averages, but daily estimated values.
The regulatory effect on intestinal transit time according to the invention is
measured concretely by scintigraphy, the patient absorbing a radioactive tracer.
It it has been observed that the regular taking, according to the invention,
of galactofructose in low doses makes it possible not only to accelerate intestinal
transit when it is too slow, but also, surprisingly, to slow it down when it is too
rapid, in particular when it is slightly too rapid. In the invention, the regulatory
effect on intestinal transit time is such that the intestinal transit time, measured
by scintigraphy, is regulated at values generally less than 40 hours, often less
than 35 hours and in certain advantageous cases less than 30 hours. These values
are also generally greater than 10 hours, often greater than 15 hours, and in
certain cases greater than 20 hours.
In a first embodiment of the invention, galactofructose used for its
regulatory effect on the intestinal transit time of mammals is done so in order to
accelerate intestinal transit in the mammals which absorb it (these mammals
typically having an intestinal transit which is too slow before beginning the
absorption). Therefore, a mammal whose intestinal transit is too slow before
having absorbed galactofructose sees its intestinal transit time, measured by
scintigraphy, reduced from a given initial value (value before absorption) to a
lower value, which lower value is less than 40 hours, often less than 35 hours
and in certain advantageous cases less than 30 hours, after it has absorbed
galactofructose incorporated into a food composition according to the dosage in
accordance with the present invention; the value after absorption in accordance
with the present invention is, moreover, generally greater than 10 hours, often
5
greater than 15 hours and in certain advantageous cases greater than 20 hours.
According to this first embodiment of the invention, the initial value (before
absorption) of the intestinal transit time may be, for example, at a value in a
range from 40 to 50 hours, in a range from 35 to 45 hours or else in a range from
30 to 40 hours. According to this first embodiment of the invention, the
reduction in the intestinal transit time (value before absorption minus value after
use in accordance with the invention) is advantageously at least 2 hours,
preferably at least 5 hours; it may be at least 10 hours, or even at least 15 hours.
In one particularly advantageous variant of this first embodiment, the
mammal whose intestinal transit is too slow before having absorbed
galactofructose is nevertheless not suffering from constipation (the intestinal
transit thereof is only slightly too slow), and said mammal is even
advantageously healthy, showing no sign of disease. The constipation may be
characterized by an intestinal transit time, measured by scintigraphy, of at least
48 hours, for example. According to this variant of the first embodiment of the
invention, the initial value (before absorption) of the intestinal transit time of the
mammal whose intestinal transit is too slow before having absorbed
galactofructose is preferably equal to at most 40 hours; furthermore, this
mammal sees its intestinal transit time reduced to a value of generally less than
35 hours, preferably less than 30 hours, after it has absorbed galactofructose
incorporated into a food composition according to the dosage in accordance with
the present invention. According to this variant of the first embodiment of the
invention, the initial value (before absorption) of the intestinal transit time of the
mammal whose intestinal transit is too slow before having absorbed
galactofructose is particularly preferably from 30 to 40 hours; furthermore, this
mammal sees its intestinal transit time reduced, so as to reach a value of
generally less than 30 hours, preferably to a value between 20 and 30 hours, after
it has absorbed galactofructose incorporated into a food composition according
to the dosage in accordance with the present invention.
In a second, particularly surprising, embodiment of the invention,
galactofructose used for its regulatory effect on the intestinal transit time of
mammals is done so in order to slow down intestinal transit in the mammals
which absorb it (these mammals typically having an intestinal transit which is
too rapid before beginning the absorption). Therefore, a mammal whose
intestinal transit is too rapid before having absorbed galactofructose sees its
intestinal transit time, measured by scintigraphy, increased from a given initial
6
value (before absorption) to a higher value, which higher value is generally
greater than 10 hours, often greater than 15 hours and in certain advantageous
cases greater than 20 hours, after it has absorbed galactofructose incorporated
into a food composition according to the dosage in accordance with the present
invention; the value after absorption in accordance with the present invention is,
moreover, generally less than 40 hours, often less than 35 hours and in certain
advantageous cases less than 30 hours. According to this second embodiment of
the invention, the initial value (before absorption) of the intestinal transit time
may be, for example, at a value included in a range from 0 to 10 hours, in a range
from 5 to 15 hours or else in a range from 10 to 20 hours. According to this
second embodiment of the invention, the increase in the intestinal transit time
(value after use in accordance with the invention minus value before absorption)
is advantageously at least 2 hours, preferably at least 5 hours; it may be at least
10 hours, or even at least 15 hours.
In one particularly advantageous variant of this second embodiment, the
mammal whose intestinal transit is too rapid before having absorbed
galactofructose is nevertheless not suffering from diarrhoea (the intestinal transit
thereof is only slightly too rapid), and said mammal is even advantageously
healthy, showing no sign of disease. The diarrhoea may be characterized by an
intestinal transit time, measured by scintigraphy, of at most 8 hours, for example.
According to this variant of the second embodiment of the invention, the initial
value (before absorption) of the intestinal transit time of the mammal whose
intestinal transit is too rapid before having absorbed galactofructose is preferably
equal to at least10 hours; furthermore, this mammal sees its intestinal transit time
increased, so as to reach a value of generally greater than 15 hours, preferably
greater than 20 hours, after it has absorbed galactofructose incorporated into a
food composition according to the dosage in accordance with the present
invention. According to this variant of the second embodiment of the invention,
the initial value (before absorption) of the intestinal transit time of the mammal
whose intestinal transit is too rapid before having absorbed galactofructose is
particularly preferably a value included in a range from 10 to 20 hours;
furthermore, this mammal sees its intestinal transit time increased, so as to reach
a value of generally greater than 20 hours, preferably a value between 20 and 30
hours, after it has absorbed galactofructose incorporated into a food composition
according to the dosage in accordance with the present invention.
7
In the invention, the daily number of stools is generally between 0.5 and
1.5, for a standardized unit stool weight value of 220 g/day.
The invention also relates to galactofructose for its regulatory effect on the
intestinal transit time of mammals, combined with its prebiotic effect on the
intestinal flora, when it is incorporated into a food composition and when said
composition is absorbed by the mammal in an amount corresponding to daily
doses of galactofructose, averaged over 30 days, of between 0.1 and 5 g,
advantageously between 0.1 and 2 g.
A prebiotic is a non-digestible food compound that can be broken down by
the microorganisms of the intestinal flora. This breakdown gives rise to an effect
on the intestinal flora of the mammal, beneficial to the health thereof since it
leads to development of certain bacteria of the flora. Among these, bifidobacteria
are known for having an important role, for example in the immune system of
the hosts. Their selective development by virtue of prebiotic compounds
(bifidogenic prebiotic effect) is therefore beneficial to the well-being of the host
mammal. Therefore, the prebiotic effect of a non-living compound refers to the
change, both in composition and in activity, of the intestinal flora of the host due
to the ingestion of this compound, when this change has a beneficial effect on the
well-being and/or the health of the host (see: Gibson and Roberfroid, J. Nutr,
125, 1401, 1995).
In the combined effect according to the invention, an increase in the
population of bifidobacteria in the intestinal flora of the host mammal is also
observed, in addition to the regulatory effect on the intestinal transit. This
increase is at least 50%. Preferably, the population is at least doubled.
Particularly preferably, the population of Bifidobacterium spp bifidobacteria,
expressed in log 10, is increased by 0.5 at least, which corresponds to a
multiplication of the population by a factor of around 3 at least. Bifidobacterium
spp bifidobacteria protect the gut against colonization by pathogenic bacteria.
This protection results, on the one hand, from the competition at the surface of
the cells, from the competition for essential nutrients, from the production of
antimicrobial agents and from the production of compounds comprising shortchain
fatty acids, which decrease the pH of the faeces and inhibit the
development of pathogenic bacteria. Bifidobacterium spp bifidobacteria are also
associated with a strengthening of the immune system, especially in children,
and with a preventive action against cancer, via a reduction in the activity of
enzymes that convert procarcinogenic substances into carcinogenic substances
8
(see von Wright et al., Eur J. Gastroenterol.Hepatol. November 1999, 11(11),
pp1195-1198).
Owing to the combined effect according to the invention, the increase in
the population of bifidobacteria does not require any probiotic in the food
composition. It is even recommended that the composition be substantially free
thereof. The expression "substantially free of probiotics" is understood to mean
that the food composition alone, in the absence of galactofructose, gives rise to
an increase in the population of Bifidobacterium spp of less than 10%, generally
of less than 5%.
The invention is preferably aimed at mammals in good health, exhibiting
no sign of disease. It makes it possible to improve their well-being. Under certain
circumstances, it also makes it possible to protect their good health.
In the same way as for the galactofructose according to the invention, the
food composition according to the invention is advantageously a regularly
absorbed composition, and preferably is intended for feeding children, such as
powdered milk for feeding infants.
In one preferred embodiment variant of the food composition according to
the invention, this is also substantially free of probiotics.
The invention also relates to a prepackaged dose of the composition
according to one of the preceding claims, comprising between 0.1 and 2 grams,
advantageously between 0.1 and 1 g of galactofructose. It is recommended to
absorb at least one such dose daily.
The invention finally relates to a process for manufacturing a composition
according to the invention, according to which a galactofructose powder, having
a water content of less than 5% by weight and an average particle size D50 of
less than 500 μm, is mixed with a foodstuff. The powder may be manufactured
according to the process described in FR2898516.
The process according to the invention is particularly advantageous when
the foodstuff is itself in powder form, as is the case of milk powders for feeding
children, for example.
The following examples serve to illustrate the invention.
Example 1
20 human volunteers, aged from 18 to 50 years old, having a body mass
index of between 20 and 30, were randomly split into two groups of 10, one
group absorbing, every day, for 30 days, a 20 cl glass of milk produced from
powdered milk to which 2.5g of Solactis® powder are added, corresponding to
9
1.5g of galactofructose, and the other group absorbing a placebo. The
galactofructose powder has the following composition, as percentage relative to
the galactofructose content:
Tagatose Fructose Galactose Epilactose Lactose
<2% <1% <14% <6% <8%
The volunteers did not display any sign of disease, in particular of
intestinal disease. They had never participated in a test relating to prebiotics or
probiotics. During the test they did not absorb any probiotic. The
Bifidobacterium spp population before the test, measured by the FISH
(Fluorescence In Situ Hybridization) technique was around 8.5 log10 cells/g
faeces on average. The initial intestinal transit time measured by scintigraphy
was 52 h in the two groups. At the end of the test (30 days), the Bifidobacterium
spp population increased to around 9 log10 in the group absorbing
galactofructose according to the invention and the transit time decreased to 22 h.
No significant variation (taking into account natural variations in measurement),
both in Bifidobacterium spp and in transit time, was observed in the placebo
group. 30 days after the end of the ingestion, the bifidobacterium population of
the galactofructose group returned to a value close to 8.75 on average.
Furthermore, it was verified that the total population of anaerobic bacteria varied
little during and after the test, both in the galactofructose group and in the
placebo group.
Example 2
20 human volunteers, aged from 18 to 50 years old, having a body mass
index of between 20 and 30, were randomly split into two groups of 10, one
group absorbing, every day, for 30 days, a 20 cl glass of milk produced from
powdered milk to which 2.5g of Solactis® powder are added, corresponding to
1.5g of galactofructose, and the other group absorbing a placebo. The
galactofructose powder has the following composition, as percentage relative to
the galactofructose content:
Tagatose Fructose Galactose Epilactose Lactose
<2% <1% <14% <6% <8%
The volunteers did not display any sign of disease, in particular of
intestinal disease. They had never participated in a test relating to prebiotics or
probiotics. During the test they did not absorb any probiotic. The initial intestinal
transit time measured by scintigraphy was 14 h in the two groups. At the end of
the test (30 days), the transit time was 24 h in the group absorbing
galactofructose according to the invention. On the other hand, no significant
10
variation (taking into account natural variations in measurement) in transit time
was observed in the placebo group.
Example 3
20 children were randomly split into two groups of 10, one group
absorbing, every day, for 30 days, a glass of milk produced from powdered milk
to which Solactis® powder is added, corresponding to 1g of galactofructose, and
the other group absorbing a placebo. The galactofructose powder has the
following composition, as percentage relative to the galactofructose content:
Tagatose Fructose Galactose Epilactose Lactose
<2% <1% <14% <6% <8%
The children did not display any sign of disease, in particular of intestinal
disease. They had never participated in a test relating to prebiotics or probiotics.
During the test they did not absorb any probiotic. The initial intestinal transit
time measured by scintigraphy was 34 h in the two groups. In the group
absorbing galactofructose according to the invention, the transit time measured
was 21 h halfway through the test (15 days) and was 24 h at the end of the test
(30 days). On the other hand, no significant variation (taking into account natural
variations in measurement) in transit time was observed in the placebo group.
11
I/We Claim:
1. Galactofructose for its regulatory effect on the intestinal transit time of
mammals, when it is incorporated into a food composition and when said
composition is absorbed by the mammal in an amount corresponding to daily
doses of galactofructose, averaged over 30 consecutive days, of between 0.1 and
5 g, advantageously between 0.1 and 2 g.
2. Galactofructose according to Claim 1, for slowing down intestinal
transit in the mammals which absorb it.
3. Galactofructose according to Claim 2, characterized in that the
mammal is not suffering from diarrhoea.
4. Galactofructose according to Claim 3, characterized in that the
mammal is healthy.
5. Galactofructose according to any one of Claims 2 to 4, characterized
in that the mammal has an intestinal transit time before absorption, measured by
scintigraphy, equal to a value included in a range from 10 to 20 hours.
6. Galactofructose according to any one of Claims 2 to 5, characterized
in that the increase in the intestinal transit time, measured by scintigraphy, is at
least 5 hours.
7. Galactofructose according to any one of the preceding claims,
characterized in that the mammal has an intestinal transit time after absorption,
measured by scintigraphy, equal to a value included in a range between 20 and
30 hours.
8. Galactofructose according to any one of the preceding claims, in
which the non-averaged daily doses of galactofructose absorbed are less than 5 g,
advantageously less than 2 g.
9. Galactofructose according to one of the preceding claims, in which the
non-averaged daily doses of galactofructose absorbed are between 0.1 and 5 g,
advantageously between 0.5 and 2 g, for at least 30 consecutive days.
12
10. Food composition comprising galactofructose for its regulatory effect
on the intestinal transit time of mammals, when the food composition is absorbed
in an amount corresponding to average daily doses of galactofructose of between
0.1 and 5 g, advantageously between 0.1 and 2 g.
11. Composition according to Claim 10, comprising less than 25% by total
weight of sugars such as fructose, epilactose, galactose or lactose relative to the
amount of galactofructose.
12. Galactofructose for its regulatory effect on the intestinal transit time of
mammals, combined with its prebiotic effect on the intestinal flora, when it is
incorporated into a food composition and when said composition is absorbed by
the mammal in an amount corresponding to daily doses of galactofructose,
averaged over 30 consecutive days, of between 0.1 and 5 g, advantageously
between 0.1 and 2 g.
13. Galactofructose according to the preceding claim, characterized in that
the regulatory effect on the intestinal transit time consists in slowing down
intestinal transit in the mammals which absorb it.
14. Prepackaged dose of the composition according to Claim 10 or 11,
comprising from 0.1 to 2 grams of galactofructose.
15. Process for manufacturing a composition according to Claim 10 or 11,
according to which a galactofructose powder, having a water content of less than
5% by weight, is mixed with a foodstuff.
Dated 30 July 2013
KONPAL RAE
IN/PA-1228
Agent for the Applicant
To,
The Controller of Patents
The Patent Office at New Delhi
13