IE50621B1 - Laxative composition - Google Patents

Abstract

A laxative composition, comprising ground psyllium seeds and senna fruits, the senna fruit being in a form substantially enveloped by swollen psyllium seeds is prepared by mixing separately ground psyllium seeds and senna fruits in a dry state, moistening the resulting ground mixture rapidly and uniformly with barely sufficient water, quickly granulating the resulting mixture and drying the same in a manner preventing substantial swelling to give a product having a residual moisture content of no more than 3.5% by weight of water and then coating the composition with a pharmacologically acceptable material.

Description

The invention relates to a laxative composition, more specifically a laxative comprising psyllium seeds and senna fruits, and to a method of preparing the same, The use of psyllium seeds (Plantaqo psyllium L.) for preparations for the regulation of intestinal activity is known. Psyllium seed has a considerable capacity for swelling and thus stimulates physical dilation of sensitive receptors of the intestinal wall.

In accordance with a known method (German Patent 1,103,520), psyllium seed is finely ground, moistened with water to form a very viscous paste, and dried in strand form, then broken up and finally sugar coated.

The action of senna fruits (Cassia anqustifolia) as a vegetable laxative is also known.

In other composite laxative medicines both psyllium seed and senna fruits are contained, and in these preparations the predominantly physical action of the psyllium seed is supported by the pharmaco20 logical stimulating action of senna fruits, to achieve a better overall effect.

The active sennosides contained in senna fruits are sensitive to oxidation and are easily oxidised to rhein, which has a certain convulsant and pain produc25 ing action. There has thus been a need for a composition which overcomes or mitigates the possibility of undesirable side effects. -3The present invention provides such a composition, i.e. a preparation in which the ground senna fruit product is protected against premature attack.

The laxative of the invention comprises ground 5 psyllium seed (I) and senna fruits (IX), the senna fruit being in a form substantially enveloped by swollen psyllium seeds.

By being substantially enveloped by the psyllium component, the senna fruit component is protected against undesirable alteration and its release is also retarded so that a longer-lasting, moderated action is achieved which is virtually free of undesirable side effects.

This protective action may be additionally stabilised and enhanced if the mixture of the two ground components psyllium seeds ovatae and sennae fructus angustifoliae is admixed with minor proportions of psyllium husks to make up for losses in the course of grinding of the psyllium seeds.

As compared to ground psyllium seeds, the use of husks as ground product features a substantially increased swelling ability by virtue of the gummy products contained therein in a substantially higher concentration. Measurement of the swelling number according to West German Pharmacopoeia DAB 8, page 24, with thirty samples each resulted in an average value of 57 ml. for each gram of ground psyllium seed husks. -4whereas for the ground psyllium seeds an average value of 15 ml. for each gram was found.

In accordance with the increased swelling ability of the ground psyllium seed husks, their addition increases the tendency of forming the desired enveloping of the dispersed sennae fructus particles, which is particularly advantageous for a pharmaceutical application.

The weight ratio of the psyllium seed portion 10 to the sennae fruit portion in the laxative composition according to the present invention is preferably in the range of 4 to 5 : 1, with a weight ratio of psyllium seed portion, psyllium seed husks portion and senna fruit portion of the ground product of approximately 52 : 2.2 : 12.4 being particularly advantageou s.

As is now recognised, psyllium seed not only contains a considerable amount of water-insoluble material but also forms an insoluble hydrolysis residue of about 30 - 35% by weight. This, together with a neutralising action of certain components of psyllium seed, seems to be the reason for the favourable characteristics of the new compositions comprising comminuted senna fruits predominantly enveloped by a protective psyllium seed coating.

The present invention also provides a method for preparing a laxative based on psyllium seeds and -5senna fruits, which method comprises mixing separately ground psyllium seeds and senna fruits in a dry state, moistening the resulting ground mixture with up to 50% by weight of water, granulating the resulting mixture and drying it in a manner such that swelling is suppressed to give a product having a residual moisture content of no more than 3.5% by weight of water and then coating the composition with a pharmacologically acceptable material.

According to a preferred embodiment, the ground psyllium seeds and senna fruits are kneaded with 30 to 40% by weight of water, adding approximately 3 to 4% by weight of ground psyllium seed husks, only a limited swelling thereby occurring. In this swollen state, the gummy conponents of the ground psyllium ovatae husks have a sufficient ability for spreading in view of a sufficient immobilisation of the water in the swollen layers but with an appropriate ability for further processing of the mass being maintained.

However, greater amounts of water cause processing problems, while the lyospheres are at sublimit values if an insufficient amount of water is added so that the spreading may not be achieved as desired.

Prior to the grinding, the psyllium seeds and senna fruits are conveniently dried to a moisture content of 3.5% by weight at a temperature of 80°C. and the sennoside content of the senna fruit conponent 621 -6is preferably adjusted to 2.0 to 2.5% by weight and more preferably to approximately 2.?% by weight by combining different batches. During the grinding operation, the temperature of the ground material should preferably not exceed 80°C.

Xn the moistening of the dry mixed ground products of psyllium seed and senna fruits with water, provision must be made to prevent substantial swelling of the ground psyllium component (represented by a swelling number of about 16), by rapid and uniform moistening and thorough mixing. However, the fines contained in the ground product of psyllium seeds swell so rapidly that the vehicle (water) becomes a mucilage, resulting in an enveloping of the sensitive senna fruit component.

We have found that, when proceeding in accordance with the process of the present invention, a favourable and beneficial pH adjustment occurs, the effect of which is that an initially acid pH (e.g. pH 5.5-6.0) is shifted towards the neutral point, i.e., pH 7.0, by the action of the components being mixed. The mixture thus exhibits a desirable characteristic, apparently by undergoing a reaction or reactions which produce alkaline components. This effect is important because sennoside products are generally sensitive to acid or alkali media, which lead to instability and undesired oxidation. Since S0621 -7the process of the present invention results in an inherently pH neutral product, the stability thereof is desirably enhanced.

According to a preferred embodiment of the present invention, in order to achieve a rapid and uniform moistening of the mixture of ground products, each time only small amounts of grinding product mixture, as well as water, should be combined successively (especially in a continuous manner) and subjected to intensive mixing in a series of mixing operations. This is preferably accomplished in a plurality of sequential screw blenders.

In this manner, a uniform paste is produced within a few minutes and the material is delivered to the granulator, which must also be a fastoperating machine. Preferably, therefore, there is used an extrusion press having a large D ratio, at the output of which a separately driven, revolving chopper provides for immediate chopping of the emerging strand into granules of sizes generally ranging around 2 to 2.5 mm.

The granulated material is preferably dried in a fluidised bed using air, a rapid, gentle drying being achieved and caking of material being prevented. We have found that the granulated material, of which only the fines are swollen with moisture, undergoes this process without appreciable shrinkage and can. -8if desired, then be subjected to a sugar-coating operation.

Psyllium husks (especially in an amount compensating for psyllium husk portions possibly lost during the comminution of the psyllium seed) and tragacanth gum are preferably added in small amounts to the mixture to be granulated. This increases the swelling component of the laxative and produces an additional binding action.

The weight ratios of tbe mixture of ground psyllium seeds and senna fruits range especially from about 4:1 to 5:1, a controlled sennoside content of about 2.5% preferably being maintained in senna fruit component by combining different batches.

Psyllium husks and tragacanth gum are preferably added in amounts of 3 to 4% by weight of husks and of 1 to 1.5% of tragacanth gum, based on the combined mixture of ground psyllium seeds and senna fruits. Psyllium seeds and senna fruits are ground separately to approximately the same grain size distribution, preferably to approximately the following sieve analysis: 99% by weight finer than 500 yum 85% by weight finer than 400 pm 50% by weight finer than 200 ^im. -9An especially preferred laxative contains especially about 75% psyllium seed, approximately 20% senna fruits, approximately 3.2% additional psyllium husks and about 0.8% gum tragacanth.

A particularly preferred embodiment of the abovedescribed product consists essentially of the following: psyllium seeds ovatae 52.00 parts by weight psyllium seeds ovatae (husks) 2.200 sennae fructus angustifoliae 12.400 10 talc 12.459 gum arabic 1.400 ferrum oxydatum E 172 Colour Index (1956) 77 452 77 499 0.697 15 77 491 gum tragacanth 0.750 oleum carvi 0.035 oleum salviae 0.035 oleum menthae piperitae 0.070 20 paraffinum subliguidum 0.240 paraffinum durum 0.111 saccharum 17.604 per 100 parts by weight of composition. A further particularly preferred embodiment 25 comprises the following components: psyllium seeds ovatae 54.200 parts by weight sennae fructus angustifoliae 12.400 -10usual additives, as described above.

During the overall preparation, a control of the bacteria number should be continuously maintained.

The mode of preparation and the type and amount of the constituents of the laxative provide advantageous properties as compared to known laxatives of this type. These advantages consist in that, by the physiologically appropriate swelling of the product, the bowel is provided with a filling which is necessary for an optimum natural bowel activity. Further, undesired side effects are eliminated, for example an irritation of the mucous membranes of the stomach and the bowel and a careful and attenuated release of the intact sennosides is ensured. These pharmacologically and clinically observed particular advantages will become better understood by way of model tests on the kinetics of the sennoside release: To evidence the protecting enveloping action of the dried-on gummy products of psyllium seed (husks) ι ground product, extraction tests were performed in j water at a temperature of 23°C. and in artificial gastric juices and artificial bowel juices (each at a temperature of 37°C.) using 12.4 g. of ground sennae fructus angustifoliae (I), a mixture of 12.4 g. ground senna fruit and 54.2 g. ground psyllium seeds (IX) and the laxative according to the invention comprising 12.4 g. sennae fruit ground products and 54.2 g. ι -11psyllium seeds ground products (III).

The above ground products were stirred in 300 ml. extraction liquid each for 10 and 30 minutes, respectively. The liquid was separated from the insolubles by centrifuging and lyophilised. After determining the weight each, the content of sennosides was determined according to the modified procedure of the European Pharmacopoeia EuAB 2 and put into a relationship with the amount of sennosides contained in the batches used for each experiment. The following Table shows the data obtained in these tests.

Tested material Percentage of extracted sennosides water artificial gastric juices artificial bowel juices 10 min 30 min 10 min 30 min 10 min 30 min I 85.2% 88.9% 55.6% 59.3% 74.1% 74.1% II 55.6% 59.3% 40.7% 44.4% 48.2% 59.3% III 13.0% 8.9% 6.7% 2.2% 3.2% 5.6% These data clearly show a retarded release of the 20 sennosides for the laxative composition according to the invention.

The retarded release of the sennosides from the laxative composition according to the invention does not result in a complete blocking of the active » 50621 -12ingredients, which, on the contrary, are substantially completely released over longer periods of time, as evidenced by the following in vitro test: The laxative composition of the invention was 5 allowed to swell overnight. Thereafter, the swollen material was mixed with water and extracted five times, with the water phase being renewed after each hour. After five hours extraction, approximately 84% of the expected sennosides could be isolated from the aqueous phases. The individual data are listed in the following Table.

Determination of the sennoside release rate from swollen laxative composition Extraction solids (g) sennosides (g) dissolved sennoside portion (%) 1 20.73 0.126 46.67 2 6.56 0.051 18.89 3 2.98 0.026 9.63 4 1.53 0.014 5.18 5 1.15 0.009 3.33 Total 0.226 83.7 Upon using artificial gastric juices and artificial bowel juices, respectively, essentially the same data are obtained. 30621 -13The above tests, which are approximated to the mean duration of residence of the drugs in the gastrointestinal tract, clearly show that essentially all of the sennosides of the sennae fruit component in the laxative composition according to the invention will be effective with the desired retardation.

The above results and further results as described in the Examples which follow, show that the laxative composition has a smooth action, free of undesired side effects, and is characterised by a particularly high tolerability, particularly as an aid to defaecation for haemorrhoid or fissure patients, before and after surgery. They may be administered in a clinical application to patients confined to bed over prolonged periods of time and may be administered also during pregnancy without concern.

Preparative Example Psyllium seeds were cleaned of dirt and foreign seeds, dried at about 80°C. to a moisture content of 3.5% and ground to a grain size distribution corresponding to the following sieve analysis: 99% finer than 500 fum 85% finer than 400 /im 50% finer than 200 frm.

In the grinding process, the material must not be heated above 80°C. -14Senna follicles were tested separately for their sennoside content and standardised at 2.2% by the mixing of different batches, if necessary. The grinding of this material to a size corresponding to the size specified above for psyllium seeds was performed in two stages, namely, a preliminary grinding and a fine grinding.

The two ground products were mixed dry with 4.4 kg. of ground psyllium husks and 1.5 kg. of tragacanth gum in the following ratio: psyllium seeds: 105.500 kg. senna fruits: 27.600 kg. husks and gum: 5.900 kg. 138.000 kg. This pre-granulate resulted, after · described granulation and dragee formation procedure, in 200 kg. of final laxative product.

The powder mixture passed from the mixing vessel to the mixing section feeding the strand extruder, in which approximately 30 - 40% of filtered water was added. This moist mass was allowed to stand for 1-2 hours in order to promote spreading of the mucilage around the senna fruit particles. The material was then rapidly mixed and fed to the extruder where it was extruded with a large D-ratio at a pressure of about 50 atmospheres excess pressure and chopped by a rotating knife at the die into -15granules from 2.1 to 2,2 mm. long. The moist granular product is to have a moisture content of 35%.

The drying operation that follows was performed in a fluidised bed dryer with vibratory feed to a residual moisture content of no more than 3.5% within about 25 minutes at an air temperature of 125°C. and an air flow rate of 8000 cubic metres per hour.

The dry granules were sifted to remove those smaller than 1 mm. and those over 3 mm., and then their bulk weight was from 510 to 530 grams per litre.

Finally, the material was formulated into dragees by contacting the above pre-granulate with a dragee suspension comprising aromatic essences, gum arabic, saccharose pigment and talc, which was applied to the pre-granulate in a conventional dragee-making machine. This resulted in a sugar-coated dragee incorporating therein a flavouring mixture of peppermint oil, caraway oil and sage oil (ratio 2:1:1) in amounts of approximately 0.1% with respect to the final product.

The bacterial count of the material was constantly inspected during the entire process.

The final product, which is the particularly preferred embodiment of the invention because of its outstanding pharmacological properties, had the following conposition (per 100 kilograms of product): psyllium seeds ovatae 52.000 kg. supplementary psyllium husks 2.200 kg. sennae fructus angustifoliae 12.400 kg. talc 12.459 kg. gum arabic 1.400 kg. ferrum oxydatum, E 172 0.697 kg.

Colour Index (1956) 77492 77499 77491 gum tragacanth 0.750 kg. oleum carvi 0.035 kg. oleum salviae 0.035 kg. oleum menthae piperitae 0.070 kg. paraffinum subliquidum 0.240 kg. paraffinum durum 0.110 kg. saccharum 17.604 kg. The above product has a swelling number of about 7.50 (at least 6.0) (determined according to West German Pharmacopoeia DAB 8), a bulk density of 0.765 to 0.905 g/ml. (determined according to DIN 53 912), a granule diameter of 1 to 3 mm. and a sennoside content of 0.25 to 0.31%, particularly of 0.27%. These parameters ensure a particularly good overall action.

A further preferred embodiment consists of the following: psyllium seeds ovatae, ground product 54.200 kg. sennae fructus angustifoliae 12.400 kg.

Usual additives as above. -17The parameters of this further preferred embodiment are in the same range.

The laxatives of the invention are characterised by their mild, reliable action combined with complete tolerability. The compositions of the invention are also characterised by stable effectiveness over long periods, no habituation phenomena having been observed.

To establish the pharmacological safety of the laxatives of the invention, the embodiment set forth in the above preparative example was tested as follows: Toxicity and side effect tests Acute toxicity was tested in rats and mice of both sexes, using 40 of each. The powdered material was suspended in water and the fresh suspension administered per os to the animals, which were observed for eight days. The precise determination of the LD,jq proved to be impossible because the toxicity was too low. Even one hundred times the daily dose recommended for human beings produced no harmful effect. ld50 (per 03) in the rat: 5 g/kg. in the mouse: 10 g/kg.

In additional tests for the subacute toxicity in rats and mice, no mortality was observed in the administration per os of 0.5, 1.0 and 2.0 g/kg. over a period of 15 days. To test for the chronic toxicity, a dose of 0.5 g/kg. and 1.0 g/kg. was administered -18per os to two groups of rats (Sprague-Dawley) of 150 g. body weight, of male and female sex.

Tests were made for weight gain, erythrocyte count, leukocyte count, differential white count, blood sugar, prothrombin time, transaminases and residual nitrogen, before and after treatment. No marked changes were observed in comparison with a control group of animals.

After the tests were completed, all of the 10 animals were killed and subjected to a complete autopsy. The weight of the spleen, liver, heart, kidneys, brain, suprarenal gland, thyroid gland, testes and hypophysis showed no marked anomalies in comparison with the control animals. Histologic15 ally, virtually no changes were observed with regard to cellular infiltration, fatty infiltration and adenomatose hyperplasia of the liver, nephrosis, sinusoidal dilation of the adrenals, cellular infiltration of the heart, adenomatose hyperplasia of the thyroid, and infiltration of the cells of the spleen and testes.

In another series of toxicity tests, the subacute toxicity of the composition of the invention, administered over thirty days, was investigated both in rats and dogs and, in still another series of safety tests, chronic toxicity was determined both in rats and dogs by administration over a period of -19180 days. Oral administration of the inventive composition for thirty consecutive days in doses five and ten times higher than those recommended for human consumption was well tolerated by rats and dogs of both sexes. Oral administration of the composition over a period of 180 days in doses two-and-a-half and five times higher than those recommended for human consumption was well tolerated by SpragueDawley rats and mongrel dogs of both sexes. During and after the treatment, there were no changes observed in the following parameters: development of body weight, haematological, blood chemistry and urinological parameters, macroscopic and microscopic examination of the principal organs. In particular, there was no incidence of bleeding or ulceration of the gastrointestinal tract.

Studies on the rabbit, with a daily administration of 1.0 g/kg. for 6 weeks to male and female animals by administration per os, gave no indication of any harmful effects as regards body weight, erythrocyte count, leukocyte count, differential white count, residual nitrogen and blood sugar.

The teratogenic action of the product was tested in rats and rabbits with daily doses of 1 g/kg. per os, which were administered from the 7th to 21st day of pregnancy in the rat and from the 7th to the 15th day in the rabbit. The foetuses were removed from the 50631 -20animals on the 21st and 27th day, respectively, and examined. No specific teratogenetic effect of the product was found and evidently the inventive composition has no effect on embryonic development.

Laxative action tests For the testing of the laxative action itself, single doses of 2.5 and 5 g/kg. were administered per os, respectively, to mice and rats. A decided increase and softening of the faeces was observed.

A definitely dose-related effect is observed 3 to 4 hours after administration. The influence of the product on intestinal motility and on the time required for the passage of the intestinal contents was tested in rats (strain Sprague-Dawley) of both sexes weighing 240 g., in groups of 10 animals each. After 24 hours of fasting, the animals were administered per os 22 ml./kg. of aqueous suspension of 10% animal charcoal and 0.5% carboxymethylcellulose, as well as 2.5 and 5 g./kg., respectively, of the product under test. Forty minutes after administration the animals were killed and the total length of the small intestine and the suspension filled length of same were measured. The following results were obtained: treatment dose g.Ag. intestinal fill length (cm.) - - 56 + 4.4 laxative 2.5 79 + 6.2 laxative 5 86 + 6.8 In another series of tests, the laxative action of the inventive composition was determined by administration of the test substance at different dosage levels to mice and rats.

The test procedure was as follows: An equal number of male and female mice (strain Swiss) with a mean body weight of 24 g. and the same number of male and female rats (strain Sprague-Dawley) with a mean body weight of 230 g. were used. After withdrawing food from the animals for 3 hours, they were housed in a compartmentalised cage. The floor of the cage was covered with filter paper in order to collect the faecal pellets of each animal. The animals which excreted soft faecal pellets were excluded from the experiment. The remaining animals were placed in the treatment cage. The test composition was administered £.o. using an oral syringe at 2.5 and 5 g/kg.

At regular time intervals, up to 8 hours after the administration of the inventive composition, the number and nature of the faecal pellets excreted by 50631 -22each animal was observed. The results are set forth in the Tables below (wherein Test Comp is the inventive composition).

Investigation of the laxative effect in the rat 5 (single dose of 2,5 and 5,0 g/kg, p.o.)_ n treatment gAg Observation period (no. of hours after administration) 2 4 6 8 H S H S' H S H S 10 controls - 2.4 0.1 3.8 0.1 4.5 0.1 4.5 0.1 10 Test Comp. 2.5 3.1 0.2 3.8 2.2 4.2 6.2 5.4 6.8 10 Test Comp. 5 3.3 4.1 3.9 6.1 4.4 7.2 4.9 9.1 H = hard faeces: No. of faecal pellets per rat S = soft faeces: No. of faecal pellets per rat Investigation of the laxative effect in the mouse (single dose of 2.5 and 5,0 g/kg. p.o.) n treatment gAg Observation period (no. of hours after administration 2 4 6 8 H S H S H S H S 20 controls - 3.1 0.1 4.2 0.1 4.4 0.2 4.5 0.2 20 Test Comp. 2.5 2.4 0.2 4.2 2.1 5.1 3.3 5.3 3.8 20 Test Comp. 5 2.6 3.4 4.4 5.6 4.6 8.2 4.6 9.8 H = hard faeces: No. of faecal pellets per mouse 25 S = soft faeces: No. of faecal pellets per mouse -23Investigation of the laxative effect in the rat (single dose of 2.5 and 5.0 g/kg. p.o.) n treatment g/'kg No. of rats with soft faeces/ No. of treated animals Hours after administration 2 4 6 8 10 controls - 0/10 0/10 2/10 2/10 10 Test Comp. 2.5 3/10 5/10 5/10 6/10 10 Test Comp. 5 3/10 7/10 10/10 10/10 With these animals obviously at a dosis above 2.5 gAg· the upper limit with regard to an increase of activity is reached.

Investigation of the laxative effect in the mouse (single dose of 2.5 and 5.0 gAg· p.o.) n treatment gAg No. of mice with soft faeces/ No. of treated animals Hours after administration 2 4 6 8 20 controls - 0/20 1/20 4/20 4/20 20 Test Comp. 2.5 4/20 8/20 10/20 17/20 20 Test Comp. 5 8/20 17/20 20/20 20/20 The results showed a distinct laxative action, demonstrated by the increased frequency of defaecation and also by a substantial increase in soft faecal pellets in comparison with hard faecal pellets. 50631 -24In a test for diuresis, a reduction of kidney secretion was observed, which appears to be connected with the increase in the enteral fluid excretion. In a test for choleretic action, virtually no significant change was detected and from this it is concluded that the product of the invention has no choleretic action. The daily food intake was also tested; virtually no change was found.

The product administered per os in doses of 1.0 10 and 2.0 g/kg. to male rats of 280 grams weight produced no perceptible changes in arterial blood pressure and heart rate. Also, no inflammatory changes in the gastrointestinal area were detected.

In summary, the test results established that 15 the inventive composition has very low toxicity, i.e., even too low to determine the Γ,ϋθθ in the in vivo experiments in which the inventive composition was administered in dosages 100 times those recommended for human therapy. No toxic effects or intolerance were observed, only laxative action, i.e. its main pharmacological property. In addition, no inflammatory changes in the gastric and intestinal regions of animals receiving one large dose of the composition or longterm treatment therewith was established and this is regarded as surprising since inflammatory changes are frequently observed in animals treated with laxatives.

In gravid animals, the administration of the inventive -?·»composition did not evoke any changes in normal foetal development and the test animals were totally comparable to those of control animals with regard to number, weight and appearance of the foetuses.

The laxative action of the inventive composition was found to occur between 3 and 4 hours after administration to the animals and was directly dosage related. The laxative action is accompanied by an acceleration of the transit time of contents through the intestine. The diuresis experiments with treated animals resulted in a diminution of urine output which can be related to the increase in enteral fluid excretion. No changes in bile secretion, smooth muscle function, arterial blood pressure or heart rate were demonstrated. Daily food intake was also not affected by the administration of the composition according to the present invention.

The laxatives of the present invention are generally administered in daily dosages of approximately 1 to 5 grams per 75 kg. of body weight to patients suffering from constipation and for the regulation of the stool. The laxatives can be formulated in a conventional manner with the addition of flavouring substances and the like. The addition of peppermint oil, caraway oil and sage oil to sugar-coated preparations have proved to be desirable in giving pleasantly administered dragees. -26When percentages are referred to hereinabove, percentages by weight is intended, unless otherwise stated.

Claims (13)

1. CLAIMS:1. Method for preparing a laxative based on psyllium seeds and senna fruits, which method comprises mixing separately ground psyllium seeds and senna fruits in 5 a dry state, moistening the resulting ground mixture with up to 50% by weight of water, granulating the resulting mixture and drying it in a manner such that swelling is suppressed to give a product having a residual moisture content of no more than 3.5% by 10 weight of water and then coating the composition with a pharmacologically acceptable material.

2. Method according to claim 1, wherein the moistening with water is carried out using an amount of water which is from about 30 to 40% by weight, 15 based on the moistened total mixture.

3. Method according to claim 1 or 2, wherein the moistening is performed by continuously mixing partial amounts of the ground mixture and water in a plurality of successive mixing stages. 20

4. Method according to claim 3, wherein the mixing is carried out in a plurality of screw mixers.

5. Method according to any of the preceding claims, wherein granulation is performed in an extrusion press fitted with a separately controllable chopping 25 knife at the press outlet. -286. Method according to any of the preceding claims, wherein the granules obtained have a particle size range of approximately 2 to 2.5 mm.

6. 7. Method according to any of the preceding claims, 5 wherein granulation is performed at approximately 50 atmospheres excess pressure.

7. 8. Method according to any of the preceding claims, wherein the granules are dried in air in a fluidised bed for approximately half an hour.

8. 10 9. Method according to any of the preceding claims, wherein psyllium seeds and senna fruits are initially ground separately to a grain size distribution of approximately 99% by weight finer than 500 ftm 15 85% by weight finer than 400 μπι 50% by weight finer than 200 ^un. 10. Method according to any of the preceding claims, wherein the ground psyllium seeds and senna fruits are mixed in a weight ratio of about 4 : 1 to 5 :1 20 (psyllium : senna).

9. 11. Method according to any of the preceding claims, wherein the sennoside content of the senna fruits is adjusted, prior to grinding thereof, to a standard value in the range of 2.0 to 2.5% by weight. 25 12. Method according to claim 11, wherein the sennoside content of the senna fruits is adjusted to a standard value of 2.2% by weight. -2913. Method according to any of the preceding claims, wherein, in the step of mixing the psyllium seeds and the senna fruits, psyllium husks and tragacanth gum are additionally added. 14. Method according to claim 13, wherein the additional husks are used in an amount of 3 to 4% by weight and the tragacanth in an amount of 1 to 1.5% by weight, based on the total amount of ground psyllium seeds and senna fruits. 15. Method according to claim 1 for preparing a laxative, substantially as hereinbefore described and exemplified. 16. Laxative, whenever prepared by the process according to any of claims 1 to 15. 17. Laxative composition, comprising ground psyllium seeds and senna fruits, the senna fruit being in a form substantially enveloped by swollen psyllium seeds. 18. Laxative composition according to claim 17, which additionally comprises supplementary psyllium husks and tragacanth gum. 19. Laxative composition according to claim 17 or 18, wherein the weight ratio of ground psyllium seeds to senna fruits is from 4 :1 to 5 : 1. 20. Laxative composition according to claim 18 or 19, comprising approximately: -3052% by weight psyllium seeds 12% by weight senna fruits 2% by weight supplementary psyllium husks and 0.8% by weight tragacanth gum. 21. Laxative composition according to any of claims 18 to 20, consisting essentially of the following: psyllium seeds ovatae supplementary psyllium husks sennae fructus angustifoliae talc gum arabic ferrum oxydatum, E 172 Colour Index (1956) 77492 77499 77491 52.000 parts by weight 2.200 parts by weight

10. 12.400 parts by weight 12.459 parts by weight 1.400 parts by weight 0.697 parts by weight gum tragacanth oleum carvi oleum salviae oleum menthae piperitae paraffinum subliquidum paraffinum durum saccharum 0.750 parts by weight 0.035 parts by weight 0.035 parts by weight 0.070 parts by weight 0.240 parts by weight 0.110 parts by weight

11. 17.604 parts by weight per 100 parts by weight of composition.

12. 22. Laxative composition according to any of claims 17 to 19, consisting essentially of the following: 60621 psyllium seeds ovata 54.200 parts by weight 12.400 parts by weight 12.459 parts by weight 1.400 parts by weight sennae fructus angustifoliae talc gum arabic 5 ferrum oxydatum, E 172 0.697 parts by weight Colour Index (1956) 77492 77499 77491 gum tragacanth 0.750 parts by weight 10 oleum carvi 0.035 parts by weight oleum salviae 0.035 parts by weight oleum menthae piperitae 0.070 parts by weight paraffinum subliquidum 0.240 parts by weight paraffinum durum 0.110 parts by weight 15 saccharum 17.604 parts by weight per 100 parts by weight of conqsosition.

13. 23. Laxative composition according to claim 17, substantially as hereinbefore described and exemplified.