Title: Lactulose-based anhydrous composition
United States Patent: 6,221,853
Inventors: Salsarulo; Odette M. (14, rue de la Belle Feuille,
92100 Boulogne-Billancourt, FR); Salsarulo; Gerard (14, rue de la Belle
Feuille, 92100 Boulogne-Billancourt, FR)
Appl. No.: 176213
Filed: October 21, 1998
Foreign Application Priority Data: Oct 21, 1997[FR] (97
The invention relates to a lactulose-based medicinal product,
characterized by the incorporation of anhydrous lactulose into a coating
vehicle, which is also anhydrous, consisting of a mixture of
pharmaceutically acceptable purified paraffinic hydrocarbons, this vehicle
having a melting point of about 37oC..+-.4oC. It is,
in particular, dosed so as to allow the administration of 3 to 5 g per day
to an adult, in particular in a single dosage intake.
Description of the Invention
Lactulose is a recognized laxative which acts, on the
basis of its osmotic power, in the intestine.
Pharmaceutically, lactulose is usually:
either in the form of a 50% solution
or in pure powdered form, but, in this case, patients ingest it with
In these presentations, the active oral doses of lactulose are high,
ranging from 10 to 30 grams/day (for an adult) in terms of pure powder
value (which often makes it necessary to take several doses during the
day). Oral administration is not without problems relating to the
tolerance of the product by the body. It is liable to result in
undesirable side effects, such as flatulence or a bloated feeling.
The aim of the invention is to provide a pharmaceutical composition which
makes it possible largely to overcome the abovementioned drawback, i.e.
which allows the daily administration of lower doses of lactulose while at
the same time retaining an equivalent laxative activity.
The composition or pharmaceutical form described in French patent No.
9013619/2688706, characterized by the incorporation of anhydrous lactulose
into a pharmaceutically acceptable vehicle for the oral route, which is
also anhydrous, having in particular a melting point of between 45oC.
and 60oC. and consisting of a mixture of purified paraffinic
hydrocarbons, already largely overcame the abovementioned drawbacks.
Indeed, not only can these lactulose-based pharmaceutical compositions be
ingested without water, and thus be taken as they are by patients, but
also the clinical working daily doses were able to be lowered to 5 to 10
grams of lactulose per day for an adult.
The present invention is an improvement of the composition described in
the French patent identified above. It results from the twofold discovery
the efficacy due to the osmotic pressure exerted during absorption of the
medicinal product of the above patent was not affected by the use, for the
coating vehicle, of a mixture of paraffinic hydrocarbons, usually
paraffinic carbon distillates containing liquid paraffin, but having a
lower melting point, in particular of about 37oC. instead of 45
to 60oC., and
the clinical working dosage of lactulose which can be administered daily
under these conditions was able to be reduced even further, resulting in
an even greater reduction in the side effects (flatulence or a bloated
feeling) of lactulose when it is used at high doses.
The composition according to the invention which contains anhydrous
lactulose coated in a vehicle which is also anhydrous consisting of a
mixture of pharmaceutically acceptable purified hydrocarbons, is thus
characterized in that the vehicle has a melting point of about 37oC..+-.4oC.,
thus equal to, or in any case close to, body temperature.
It should be noted that the abovementioned melting point, of about 37oC.,
corresponds to a capillary melting point which can be measured with a
variability of .+-.5% by carrying out the technique described in the
French Pharmacopoeia, 10th edition, 1983, V.611.
According to an additional preferred characteristic of the invention, the
anhydrous lactulose used in these compositions is micronized, the particle
sizes advantageously being between 75 and 150 .mu.m. The incorporation of
anhydrous lactulose thus micronized into the vehicle, in particular the
coating of its particles in the vehicle, results in greater dispersion of
the lactulose in the composition and an additional increase in its osmotic
The result of this is that the clinical working doses of lactulose which
can be administered to an adult in this new form can be lowered even
further, and in particular can be reduced to 3.5 to 5 grams per day,
instead of the daily doses which still required the use of the
compositions of the above paten: 5 to 10 grams of lactulose per day for an
It goes without saying that the composition thus obtained does not
necessarily represent the final pharmaceutical presentation as will be
given to patients. This presentation can also contain other excipients
provided that the anhydrous nature of the lactulose, which is the basis of
its osmotic pressure, is maintained, and as long as the final composition
does indeed contain the abovementioned working doses of lactulose.
As in the case of the above patent, the hydrocarbon-based vehicle
advantageously consists of anhydrous distillates of paraffinic carbons,
refined to a level which makes them completely harmless and, if need be,
selected such that this mixture has a melting point of about 37oC.,
by optional and complementary addition of pharmacopoeia-grade liquid
paraffin. The preferred vehicle thus consists of a mixture of paraffinic
carbon distillates containing liquid paraffin, it being understood that
the relative proportions of these constituents are to be selected by a
person skilled in the art on the basis of the melting point chosen, of
about 37oC. By way of non-limiting example, it will be
indicated that the proportion of liquid paraffin will, as a result, often
be within a proportion ranging from 1/4 to 3/4 of the weight of the
composition. It goes without saying that the liquid paraffin can even be
left out if the mixture of paraffinic carbon distillates itself already
has a melting point of about 37oC.
Three compositions which satisfy the conditions of the invention are given
below, as examples, it nevertheless being understood that they should in
no way be considered as being limiting in nature.
The proportion of the coating (paraffinic carbons and liquid paraffin) is
about 1 to 2 times the amount of lactulose. Thus, the proportion of
lactulose relative to the entire composition is advantageously from about
30 to 45% by weight of the total composition, and, for example, of about
3.5 g of lactulose per 6.5 g of hydrocarbons.
The use of the composition according to the invention is naturally
accompanied by the advantages already mentioned with regard to the
invention described in the above patent, but to an even greater beneficial
degree since it allows, for the same efficacy, an additional reduction in
dosage, in particular by virtue of the additional reduction of the
effective doses of lactulose, to 3 to 5 grams per day instead of the 5 to
10 grams per day required for the composition of the prior patent.
Advantageously, the composition is in a pharmaceutical form such that it
allows the administration of effective daily doses of about 3.5 to 5 grams
of lactulose per day, preferably in a single dosage intake. At this
reduced dose, the tolerance is greatly improved.
Claim 1 of 14 Claims
What is claimed is:
1. A laxative composition having a reduced amount of lactulose with a
clinical working dose of 5 or less grams per day comprising anhydrous
lactulose incorporated into an anhydrous coating vehicle, said coating
vehicle comprising a mixture of pharmaceutically acceptable purified
paraffinic hydrocarbons, and said vehicle having a melting point of about
37oC..+-.4oC. and wherein said lactulose comprises
micronized particles of 75 to 150 micrometers (microns).
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