FR2728462A1 - Powdered laxative compsn. reducing risk of fibre fermentation in colon - Google Patents

Abstract

Dry powdered compsn. contains soya cotyledon fibres (I) and liq. paraffin (II) dispersed in the form of microspheres together with one or more excipients, diluents and inert non-toxic supports. Also claimed is the prepn. of the compsn. Wt. ratio of (I):(II) is 10:1-2:10 (esp. 4:1-1:2). The compsn. pref. also contain an alkyl cellulose (methyl-, ethyl-, hydroxyethyl- or hydroxypropyl-cellulose which improves the physical properties of the cotyledon powder. In addn., inositol or sorbitol, sweeteners such as saccharin or aspartame, flavourings such as vanillin, ethyl vanillin and preservatives such as sorbic acid and sorbates, ascorbic acid and ascorbates. Powder is suspended in water to give a suspension that is pleasant to drink.

Description

NEW LAXATIVE COMPOSITIONS
AND THEIR PROCESS FOR OBTAINING
The present invention relates to the field of therapeutic chemistry and more particularly to the production of new pharmaceutical formulations.

More specifically, it relates to pharmaceutical compositions with laxative action formed by a bulk laxative and a lubricant laxative.

It specifically relates to new pharmaceutical compositions in which the ballast laxative is a preparation based on soy cotyledon fibers and the lubricant laxative is a dry powdery preparation based on liquid paraffin dispersed in the form of microspheres, in combination or in mixture with one or more excipients, diluents or inert carriers, pharmacologically compatible.

We know the interest of soy cotyledon fiber in the treatment or in the regulation of the functioning of intestinal transit. Soy cotyledon fiber contains a relatively large percentage of water-soluble dietary fiber, made up of acidic pectin-like polysaccharides and neutral arabinogalactans. The soy cotyledon fibers being formed for approximately 75% of dietary fibers, therefore, the insoluble fraction of these fibers varies according to the analysis methods between 55 and 70% of the total weight.

As a result, soybean cotyledon fibers have multiple physiological functions and, in particular, a direct effect on the digestive tract by regulating the use of food and on the functioning of the intestine by improving the moisture content of the food bolus. . In addition, clinical studies have shown that preparations based on soybean cotyledon fibers significantly increase the weight of the fecal bowl and normalize the moisture content of this fecal bowl as well as the transit time.

However, the beneficial effects of soy cotyledon fibers are only achieved by daily administration of 13 to 60 g of preparation. This poses a serious problem of absorption and tolerance, in particular because of the fermentable nature in the intestine of such a preparation.

As described by GS LO in "New Development in Dietary Fixer1 p.49, the advantage of a large soluble fraction of dietary fibers like those of soya is to increase the viscosity in the stomach, as do Pectin and gums On the contrary, the sources of insoluble fibers purely cellulosic have these effects only in a very limited way, but contribute to a laxative effect by reducing the transit time and by increasing the volume of the fecal bowl. , cellulosic fibers (hemi-celluloses, a-celluloses) give rise to volatile fatty acids and to various hydrocarbon products, which appreciably and unfavorably affects the physiological responses to the administration of dietary cellulose fibers.

This is why it has proven useful to combine with the soy cotyledon fibers a significant proportion of a lubricating laxative which further accelerates intestinal transit and thus limits the risk of fermentation in the colon, and which increases the effect. laxative of soy cotyledon fibers.

The most suitable lubricant laxative is liquid paraffin, also called paraffin oil, and its most suitable mode of presentation is the presentation in the form of microspheres, possibly coated, to form a powdery presentation, perfectly fluid and mixing well, without demixing with soy cotyledon fibers.

These microspheres are hard enough to form a perfectly dry powder which does not allow paraffin oil to ooze through the outer shell. These microspheres can therefore be mixed with the soy cotyledon fiber powder also in powder form and form a completely homogeneous powder.

This mixture can then be supplemented with inert excipients such as lactose, mannitol, tricalcium phosphate, magnesium carbonate, colloidal silica, sodium citrate or sodium phosphate. The powder thus formed can also be supplemented with flavoring agents such as inositol or sorbitol, sweetening agents such as saccharin or aspartame, flavoring agents such as vanillin,
Ethylvanillin, furaneol or linalylthiol, preservatives such as sorbic acid or an alkali metal sorbate, ascorbic acid or sodium ascorbate.

The powder mixture is distributed in unit doses or stored loose in glass vials. It is intended to be poured into a determined volume of water in which the soy fiber powder swells, forming a mucilage which includes the paraffin oil microspheres. This gives a fluid emulsion that is perfectly pleasant to taste, easily ingested and of incomparable efficiency.

In fact, the effects specific to each of the laxative constituents of the compositions according to the invention not only add up but, moreover, mutually reinforce each other with real synergy. It emerges from clinical studies carried out with the compositions according to the invention with respect to the powder of soybean fibers alone, that the loading action of the soybean fiber is considerably reinforced and facilitated, by the addition of a lubricant laxative. .

In addition, the use of paraffin oil in the form of microspheres avoids the oozing of the oil and the unpleasant digestive disorders which result therefrom. The tolerance of the mixture is excellent, the acceptability is without any measure with that of each of the active components taken in isolation (fine preparation obtained by grinding the soy cotyledons or liquid paraffin oil dispersed in a carboxymethylcellulose gel).

In the pharmaceutical compositions according to the invention, the weight ratio between the powder of soya fibers and the microspheres of paraffin oil varies from 10 parts of soya fibers per 1 part by weight of paraffin oil to 2 parts of fibers soy per 10 parts by weight of paraffin oil. The preferred proportions vary from 4 parts of soya fibers for 1 part of paraffin oil in microspheres to 1 part of soya fibers for 2 parts of paraffin oil.

Preferably, the pharmaceutical compositions according to the invention are presented in the form of powder sachets or powder packages, containing 4 to 10 g of mixture.

A particularly preferred composition is that which contains soy cotyledon fibers and the paraffin oil microspheres in equal parts. The preferred administration unit is that which contains 6 to 7 g of the mixture of active ingredients in a polyethylene bag covered with aluminum foil. The mixture according to the invention can also be distributed in well-closed glass vials and the administration of the mixture will be in the form of teaspoons with 50 to 100 ml of water.

The dosage is one or two sachets per day, for a period which does not exceed five days.

For reasons of ease of mixing, it has been found to be advantageous to incorporate into the soybean cotyledon powder, an alkyl cellulose which contributes to improving the physical properties of the soybean cotyledon powder.

Among the alkyl celluloses, methylcellulose, ethylcellulose, hydroxyethylcellulose or hydroxypropylcellulose are preferably used. The alkylcellulose and soy cotyledon powder mixture is produced by spraying the soy cotyledon powder with an alkylcellulose solution in an alkanol and then drying the mixture thus formed in a fluidized bed drier or in an oven with forced air circulation. then grinding the mass thus obtained and sieving it.

Preferably, the alkylcellulose is an ethylcellulose and, in particular, an ethylcellulose having from 42 to 49% of ethoxy groups, soluble in the lower alkanols. For the soaking of the soy cotyledon powder, a solution of ethylcellulose in isopropranol is preferably used at a concentration ranging from 40 to 50%. The ethylcellulose solution in the alkanol can then be diluted with an appropriate amount of water to improve the tackiness qualities of the mixture.

The amount of water incorporated into the alkanolic solution can vary from 14 to 70% of the amount of alkanol used.

The crushed soybean cotyledon fibers, thus coated and sieved, have a great fluidity which allows their incorporation into the liquid paraffin microspheres without risk of demixing and above all, with the assurance that the mixture will be completely homogeneous and will be preserved. perfectly.

The pharmaceutical compositions according to the invention are precious medicaments for treating constipation, especially in the elderly, the bedridden, pregnant women, women who have recently given birth or subjects who are to undergo abdominal surgery or an intestinal radiograph.

The invention also relates to a process for obtaining laxative compositions according to the invention which consists in first producing a soy cotyledon powder by grinding the cotyledons then separation of the integuments, spraying very fine tegument followed by rotary sieving, then incorporates this very fine powder (Hull) into paraffin oil microspheres until a homogeneous mixture is obtained and final sieving of the mixture which is diluted with an inert excipient then sweeten and / or flavor, if desired, and distribute as a unit.

The following examples illustrate the invention, they do not limit it in any way:
EXAMPLE I
6.6 g sachets of the mixture
A soy cotyledon powder is produced beforehand by drying, after harvest, the said cotyledons until the integuments fold. After threshing and winnowing, the integuments are screened on a cell sieve. The integuments are separated by successive screenings (6 or 7) through ball mills and then calibrated by passage over a sieve.

The sieved powder, formed from successive shreds of seed coats, is then pulverized using a flail mill (Promill) coupled to a reception cone followed by a rotary sieve fitted with a 400 µm mesh sieve.

25 kg of the soy cotyledon powder thus prepared are then mixed with 28 kg of paraffin oil microspheres until a homogeneous mixture is obtained. The powder is sieved through a 200 sieve and the very fluid mixture is sweetened with 0.100 g of calcium saccharinate and 0.200 g of orange essence.

The mixture is then divided into sachets of about 6.6 g, containing the mixture in equal proportions of soy cotyledon powder and paraffin oil.

Preparation of micro parhers of paraffin oil
Cold preparation is made of 100 ml of a 5% gelatin solution in a container fitted with a powerful mechanical stirring device. 120.50 g of paraffin oil are added to this solution in small portions and the stirring is continued until a fine emulsion is obtained. The gelatin droplets are coacerved by adding a 25% ammonium sulphate solution. It is filtered to separate the excess oily phase which has not been included in the gelatin and the saline solution. The microspheres are then suspended in a 40% formalin solution for 30 minutes with vigorous stirring, then separated and dried in an oven at a temperature below 40t. The microspheres are in the form of small, easily flowing, odorless and colorless grains. They are then mixed with 10% lactose and 1% talc to improve their fluidity.

EXAMPLE II
10 9 mix bags
400 g of soy cotyledon powder of soybean obtained as in Example I are mixed with 250 g of microspheres of paraffin oil until perfect homogeneity. 60 g of tricalcium phosphate and 40 g of colloidal silica (sieve 200) are added to the mixture. The mixture is then distributed into 10 g sachets.

Claims (8)

CLAIMS inert pharmacologically compatible supports. in combination or in admixture with one or more excipients, diluents or pulverulent based on liquid paraffin dispersed in the form of microspheres, soy cotyledon fibers and the lubricant laxative is a dry laxative lubricant preparation in which the ballast laxative is a preparation based on  1 0-New pharmaceutical compositions formed by a ballast laxative and a  soy fibers per 10 parts by weight of paraffin oil.  parts of soy fiber per 1 part by weight of paraffin oil to 2 parts of  soy fiber powder and paraffin oil microspheres ranges from 10  2 -Compositions according to claim 1 "wherein the weight ratio between the  for 2 parts of paraffin oil.  soy for 1 part of paraffin oil in microspheres to 1 part of soy fibers  ratio of soy fibers to paraffin oil vary from 4 parts of fiber to  3 - Compositions according to claim 1 "or claim 2" wherein the  an alkylcellulose is incorporated into the mixture of active principles.  4 -Pharmaceutical composition according to one of claims 1 to 3 in which  hydroxypropylcellulose.  the alkylcellulose is methylcellulose, ethylcellulose, hydroxyethylcellulose or  5 -Pharmaceutical composition according to claim 4 "wherein  conservation.  a sweetening agent and / or a flavoring agent and / or a flavoring agent  an inert excipient and / or a flavoring agent and / or  6 -Pharmaceutical composition according to one of claims 1 to 5 in which  unitary.  in the form of a sachet of 4 to 10 g of mixture of active ingredients per dose  7 -Pharmaceutical composition according to one of claims 1 to 6 "presented  and / or flavor if desired and distribute in unit intake.  final sieving of the mixture which is diluted with an inert excipient then sweetened  paraffin oil microspheres until a homogeneous mixture is obtained and  integuments, spraying the integuments and incorporating this powder into the  a soy cotyledon powder by grinding said cotyledons and then separating  claims 1 to 7 "which consists of what is carried out at first  8 "- Process for obtaining pharmaceutical compositions according to one of