CA1167769A - Laxative composition comprising psyllium seeds and senna fruits and method for the preparation thereof - Google Patents

Laxative composition comprising psyllium seeds and senna fruits and method for the preparation thereof

Info

Publication number
CA1167769A
CA1167769A CA000368439A CA368439A CA1167769A CA 1167769 A CA1167769 A CA 1167769A CA 000368439 A CA000368439 A CA 000368439A CA 368439 A CA368439 A CA 368439A CA 1167769 A CA1167769 A CA 1167769A
Authority
CA
Canada
Prior art keywords
weight
psyllium
senna
parts
fruits
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired
Application number
CA000368439A
Other languages
French (fr)
Inventor
Rolf Madaus
Klaus Gorler
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Madaus Holding GmbH
Original Assignee
Dr Madaus GmbH and Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dr Madaus GmbH and Co filed Critical Dr Madaus GmbH and Co
Application granted granted Critical
Publication of CA1167769A publication Critical patent/CA1167769A/en
Expired legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/23Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/481Astragalus (milkvetch)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/48Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/482Cassia, e.g. golden shower tree
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/534Mentha (mint)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537Salvia (sage)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/68Plantaginaceae (Plantain Family)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/899Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10Laxatives

Landscapes

  • Health & Medical Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Epidemiology (AREA)
  • Botany (AREA)
  • Mycology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Biotechnology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicinal Preparation (AREA)

Abstract

Abstract of the Disclosure Laxative compositions having particularly mild and well-tolerated action, not accompanied by toxic or side-effects, based on psyllium seeds and senna fruits are prepared by mixing separately ground psyllium seeds and senna fruits in a dry state, moistening the resulting ground mixture rapidly and uniformly with water, quickly granulating the resulting mixture and drying same in a manner preventing substantial swelling of the product to a residual moisture content of no more than 3.5% and then coating the composition with a pharmacologically acceptable material.

Description

1 ~ 67 ~69 The invention relates to a laxative composition, more specifically a laxative comprisirlg psylli-~n 5eeds and senna fruits, and to a method of preparin~ the same, The use of psyllium seeds (Planta~ psyllium L.) for preparations.for the regulatilDn of intestinal activity is known. Psyllium seed has a c3nsiderable capacity ~or swell-ing and thus stimulates physical dilation of sensitive receptors of the intestinal wall. In accordance with a known method (German Patent 1,103,5Z0), psyllium seed is ; lO finely ground, moistened with.water to form a very viscouspaste, and dried in strand form, then broken up and finally sugar coated.

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

In other composite laxative medicines both psyllium seed and senna fruits are contained, and in these preparati~ns the predom;nantly physical action of the psyllium seed is supported by the pharmacolo~ical stimulating action of senna ~ fruits, to achieve a better overall effect.

; 20 The active sennosides contained in senna fruits are sensi~i~e to oxidation and are easily oxidized to the rhein, which has a certain convulsant and pain producing action. There ha~ thus been a need for a composi~ion which overcomes or mitigates the possibility of un-desirable side effects.
.

- 1 ~' ,; I

, , ' ~ .

7 ~ 9 ~he present invention provides such a com-position, i.e., a preparation in which the ground senna fruit product is protected against premature attack.
The laxative of the invention comprises ground psyllium seed(I) and senna fruits 1II) and is characterized in that component II is in a form in which it is largely enveloped by dried-on com-ponent I.
Thus in one aspect of the invention there is provided a laxative composition comprising ground psylliu~l seeds and senna fruits wherein said senna fruits are in a form substantially enveloped by swollen psyllium seeds~
In a particular embodiment, the combination comprising the senna fruits enveloped by said psyllium, seeds has a residual moisture content of no more than 3.5% by weight of water, and the combination is coated with a pharmacologically acceptable material.
- By being substantially enveloped by the psyllium component, the senna fruit component is protected against undesirable alteration and its release is furthermore retarded, so that a longer-lasting, moderated action virtually free of undesirable side effects is achieved.

, t 11 ~69 ~rhis protective action may additionally be stabllized and enhanced if the mixture of the two ground cornponents psyllium seeds ovatae and sennae fructus angutifoliae further includes with minor proportions of hus~s to make up for losses in the course of grinding of the psyllium seeds.
As compared to ground psyllium seads the use of husks as ground product features a substantially increa~ed swelling ability by virtue of the muci~
products contained therein in a substantially higher concentration. Measures of the swelling number according to West German Pharmakopoea DAB 8, page 24, with thirty samples each resulted in an average value of 57 ml for each gram of ground psyllium seed husks whereas 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.
~he weight ratio of the psyllium seed portion to the sennae fruit portion in the laxative ~' .

~67~9 composition according to the invention is preferably in the range of 4 to 5 : 1, with a weight ratio of psyllium saed portion, psyllium seed husks portion and senna fruit portion of the ground product of approximately 52 : ~,2 : 12,4 being particularly advantageous .
As now recognized psyllium seed not only contains a considerable amolmt of material insoluble in water, but also forms an insoluble hydrolysis residue of about 30-35%. This together with a neutralizing action of certain components of psyllium seed, seems to be the reason for the favourable chara-cteristics of the new compositions comprising com-minuted senna fruits prevailingly enveloped by a protective psyllium seed coating.
In accordance with another aspect of the invention there is provided a process for preparing the laxative composition in which separately ground psyllium seeds and senna fruits are mixed together dry, and the-mixture, rapidly and uniformly moistened with ~ water, is so quickly granulated and dried that sub-`~ stantial swelling of the product is suppressed, and the granules, dried to a residual moisture content of ; no more than 3.5%, are then coated with a pharmacolo.-gically acceptable carrier.

-\ j I :~ 6~7769 The mixture may, for example, be moistened with about 50% water.
The pharmacologically acceptable carrier is suitably a sugar coating.
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, whereby only a limited swelling occurs. In this swollen state the mucic products 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, with an appropriate ability ~ for further processing of the mass being maintained ; 15 nevertheless. Greater amounts of water, however, cause processing problems, while the lyospheres are at sublimit values upon addition of insufficient amounts of water so that the spreading may not be achieved as desired.
: 20 ~rior to the grinding the psyllium seeds and senna fruits are conveniently d*~ed to a moisture content of 3.5% at a temperature of 80C and the sennoside content of the senna fruit component is adjusted at 2.0 to 2.5% by weight, preferably at approximately 2.2% by weight by combining different ~, ,, 1 1 6'~769 lots. During the grinding operation the temperature of the ground material should not exceed 80C.
In 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. The fines contained in the ground product of psyllium seeds, however, swell so rapidly that the vehicle - 5a -t 1 67~69 1 (water) becomes a mucilage resulting in an enveloping of the
2 sensitive senna fruit component.

4 It has been found that when proceeding in accordance with the process of the invention, there occurs a favor-6 able and beneficial pH adjustment, the e~fect of which is 7 that an initially acid pH (e.g., pH 5.5-6.0) is shifted 8 toward the neutral point, i.e., pH 7.o, by action of the 9 components being mixed; the mixture thus exhibits a lo desirable characteristic, apparently by undergoing a reac 11 tion or reactions which produce alkaline components. This 12 effect is important because sennoside products are 13 generally sensitive to acid or alkali media, which lead to 14 instability and undesired oxidation; since the process of the invention leads to an inherently pH neutral product, 16 the stability thereof is desirably enhanced.

18 In order to achieve a rapid and uniform moistening 19 of the mixture of ground products, each time only small amounts of grinding product mixture, as well as water, 21 should be combined successively ~especially in a continous : t 22 matter) and subjected to intensive mixing in a series of 23 mixing oper~tions. Preferably this is accomplished in a 24 plurality of sequential screw blenders.

26 In this manner, a uniform paste is produced within a 27 few minutes and the material is deliverd to the granulator 28 which must also be a fast-operating machine. Preferably, 29 therefore, an extrusion press having a large D ratio, at whose output a separately drive, revolving chopper provi-des for immediate chopping of the emerging strand into . granules of sizes ranging around 2 to 2.5 mm, is used.

. .

.

t ~ 67 1~9 ~he granu]~tcd material ; r l~rer~r_bly ~ied in a fluidized bed using air, in which a rapld, gentle drying is achieved, and caking of material is prevented We found that the granulated materialt of which only the fines are swollen with moisture, urdergoes this process without appreciable shrinkage and can be delivered in the resultant form to the fina, sugar-coated operation.

Preferably, psyllium husks (especially in an amount compensating for psyllium husk portions posSibly lost during the comminution of the psyllium seed) ànd tragacanth gum are added in small amounts to the mixture to be granu-lated; this increases the swelling component of the laxa-tive and produces an additional binding action.

The weight ratios of ad.nixture of the ground psyllium seeds and senna ~ruits ~nges especially from about 4 : 1 to 5:1, a controlled sennoside content of about 2.5 % being maintained in senna fruit component by combining different lots. Psyllium husks and t.agacanth gum are added, preferab-`~ ly in amounts of 3 to 4 % by weight (husks) and 1 to 1.5 %
(tragacanth gum), based on the combined mixture of ground psyllium seeds and senna frllits.
' Psyllium seeds and senna fruits are ground separately to approximately the same grain size distribution, pre ferably to approximately the following sieve analysis:
99 % finer than sbo ~um ¦ 85 % finer than 40O ~m 50 % finer than 200 ~m _ 7 ~

.. . 1 ~

1 An especially preferred laxative contains especially 2 about 75 % psyllium seed, approximately 20 % senna fruits,
3 approximately 3.2 % additional psyllium husks, and about
4 o.8 % gum tragacanth.
6 A particularly preferred embodiment of the above 7 described product consists essentially of the following:
9 psyllium seeds ovatae 52,ooo parts by weight lo psyllium seeds ovatae (husks) 2,200 11 sennae fructu.s angustifoliae 12,400 12 talcum . 12 9 459 13 gum arabic 1,400 14 ferrum oxydatum E 172 o,697 Color Index (1956) 77 452 18 gum tragacanth o,750 19 oleum carvi o,o35 oleum slaviae o,o35 21 oleum menthae piperitae o,o70 22 paraffinum subliquidum o,240 23 - paraffinum durum ~ o,111 24 saccharum 17,604 25 per loo parts by weight of composition.

27 A further particularly preferred embodiment comprises 28 the following components:
29 psyllium seeds ovataei 54,200 parts by weight sennae fructus angustifoliae 12,400 usual additives, as described above.

,J ' I 1 ~7~9 During the overall preparation a control o~ the bacteria number should be continously maintained.

The mode o~ 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 corlsist 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 eli-minated, for example an irritation of the mucuous membranes of the stomach and the bowel and a careful and attenuated release of the intact sennosides is ensured. These pharma-cologically and clinically observed particular advantages will become.better understood by way of model tests on the lS kinetics of the sennoside release:

To evidence the protecting enveloping action of the dried-on mucic products of psyllium seed (husks) ground products, extraction tests were performed in water of a ; temperature of 23 C and in artificial gastric juices and artificial bowel juices (each at a temperature of 37 Ct using 12,4 g of ground sennae fructus angustifoliae ~I), a mixture of 12,4 g ground sennae fruit and 54,2 g ground psyllium seeds ~II) and the laxative-according to the invention comprising 12,4 g sennae fruit ground products and 54,2 g psyllium seeds ground products ~III).

_ 9 _ .

1 1, ~'7 ~'69 1 ¦ The above ground products were stirred in 300 ml 2 ¦ extraction liquid each for lo and 30 minutes, respectively.
3 ¦ The liquid was separated from the insolubles by centrifuging 4 1 and lyophilized. After determining the weight each, the 1 content of sennosides was determined according to the modi-6 ¦ fied procedure of the European Pharmakopoea EuA~ 2 and 7 1 put into a relationship with the amount of sennosides 8 1 contained in the lots used for each experiment. The 9 ¦ following table shows the data obtained in these tests.
lo I
11 ¦ Tested Percentage of extracted Sennosides l material lZ Water artificial artificial 13 juices bowel juices 14 _ 10 min 30 minlo min30 minlo min 30 min _ ____ _ _ __ 16I 85,2 % 88,9 %55,6 %59,3 %74,1 % 74,1 %
17II 55,6 % 59,3 %40,7 %44,4 %48,2 % 59,3 %

III 13,o % 8,9 % 6,7 % 2,2 %3,2 % 5,6 %
1 9 ~
These data clearly show a retarded release of the 21 sennosides for the laxative composition according to the 22 invention.
23 .
24 The retarded release of the sennosides from the laxa-25 tive composition according to the invention does not result 26 in a complete blocking of the active ingredients, which, 27 to the contrary are substantially completely released over 28 longer periods of time as evidenced by the following in 29 vitro test:

-lo _ .' ,.~ .

1 ~ 6 9 l The laxative composition of` the invention was allowed 2 to swell overnight. Thereafter the swollen material was 3 additioned with water and extracted five times with the 4 water phase being renewed after each hour. After five hours extraction approximately 84 % of the expected sennosides 6 could be isolated from the aqueous phases. The individual 7 data are listed in the following table.

9 Determination of the Sennoside Release Rate from Swollen lo Laxative Composition ~ Extraction Solids (g) Sennosides (g9 dissolved 12 Sennos~de 13 __ _ _portion ( 14 1. 20,73 o,126 ~i6,67 2. '6,56 o,o51 18,89 16 _ _ __ _ _ 17 3. 2,98 o,o26 9,63 18 4. 1,53 o,ol4 5,18
5. 1,15 o,oo9 3,33 22 Total o,226 83,7 24 Upon using artificial gastric juices and artificial bowel juices, respectively, essentially the same data are 26 obtained.

28 The above tests, which are approximated to the mean 29 duration of residence of the drugs in the gastro-intestinal tract clearly show tha' essentially all of the Sennosides o~ the sennae fruit component in the laxative composition ~ ~67~69 1 according to the invention will be effective with the 2 desired retardation.

4 The above results and ~urther results as described in the examples which ~ollow, show that the laxative compo-
6 sition has a smooth action free o~ undesired side ef~ects
7 and is characterized by a particularly high tolerability,
8 particularly as an aid to defacation ~or maemorrhoid or
9 ~issure patients be~ore and after surgery. They may be ad-ministered in a clinical application to patients con~ined 11 to bed over prolonged periods of time and may be admini-12 stered also during pregnancy without concern.

16 Psyllium seeds were cleaned o~ dirt and ~oreign seeds, 17 dried at about 80 C to a moisture content of 3.5 %, and 18 ground to a grain size distribution corresponding to the 19 ~ollowing sieve analysis 99 % finer than 500 um 21 85 % finer than 400 um 22 50 % finer than 200 um.

24 In the grinding process the material must not be heated above 80 C.

27 Senna ~ollicles were tested separately for their 28 sennoside content and standardized at 2.2 % by the ~ixing 2g o~ different lots, if necessary. The grinding o~ this material to a size corresponding to the size speci~ied above Eor psvllium sssd as perE rms~ in - 12 _ 1 3 ~7'i'69 l two stages, name]y a preliminary grinding and a fine 2 grinding.

4 The gwo ground products were mixed dry with 4.4 kg of ground psyllium husks and 1.5 kg of tragacanth gum in 6 the following ratio:
7 psyllium seeds:105.500 kg 8 senna fruits:27. 600 kg 9 husks and gum:5.900 k_ lo 138.ooo kg .~ This pre-granulate resulted, after the below-described 13 granulation and dragee formation procedure~ in 200 kg 14 of final laxative product.

16 The powder mixture passed from the mixing vessel to 17 the mixing section feeding the strand extruder, in which 18 approximately 30-40 % of filtered water was added. This 19 moist mass was allowed to stand for 1-2 hours in order to promote spreading of the mucilage around the senna fruit 21 particles. The material was then rapidly mixed and fed to , 22 the extruder where it was extruded with a large D-ratio 23 at a pressure of about 50 atmospheres excess pressure and 24 chopped by a rotating knife at the die into granules from 2.1 to 2.2 mm long. The moist granular product is to have 26 a moisture content of 35 %.

28 The drying operation that follows was performed in 29 a fluidized bed dryer with vibratory feed, to a residual moisture content of no more than 3.5 % within about 25 mi-nutes at an air temperature of 125 C and an air flow rate of 8000 cubic meters per hour.
,- . , ~, ~', . .' .

.~ . I ~6'7769 1 1 The dry granules were sif'ted to remoi/e those sma]ler 2 1 than 1 mm and those over 3 mm, and then their buld weight 3 1 was from 510 to 530 grams per liter. Finally the material 4 1 was formulated into dragees by contacting the above "pre-1 granulate" with a dragee suspension comprising aromatic 6 1 essences, gum arabic, saccharose pigment and talcum which 7 ¦ was applied to the pre-granulate in a conventional dragge-8 ¦ making machine. This resulted in a sugar-coated dragee in-9 1 corporating therein a flavoring mixture of peppermint oil, lo 1 caraway oil and sage oil (ratio 2:1:1) in amounts of approx 11 ¦ o,1 % with respect to the final product. The bacteria count 1? 1 of the material was constantly inspected during the entire 13 ¦ process.
14 1 .
The final product, which is the particularly preferred 16 embodiment of the invention because of its outstanding 17 pharmacological properties, had the following composition 18 (per loo kilograms of product):
19 Psyllium seeds ovatae 52.ooo kg Supplementary Psyllium husks 2.200 kg Sennae fructus angustifoliae 12.400 kg Talcum 12.459 kg 21 Gum arabic 1.400 kg Ferrum oxydatum, E 172 o.697 kg 22 Color Index (1956) 77492 Gum tragacanth o.750 kg 24 Oleum carvi o.o35 kg Oleum salviae o.o35 kg Oleum menthae piperitae o.o70 kg Paraffinum subliquidum o.240 kg 26 Paraffinum durumo.110 kg 27 Saccharum 17.604 kg 28 The above product has a swelling number of' about 7.50 29 (at leat 6.o) (determined accordi,ng to West German Pharma-kopoea DAB 8), a bulk density of o.765 to o.905 g/ml ., 1 1~7769 1 ¦ (determined according to DIN 53 912), a granula diameter 2 ¦ of 1 to 3 mm and a sennoside content of o, 25 % to o,31 %, 3 ¦ particularly of o,27 %. These parameters ensure a particu-4 ¦ larly good overall act~on.
6 ¦ A further preferred embodiment consists of the 7 1 following:
3 ¦ Psyllium seeds ovatae, ground product 54. 200 kg 9 ¦ Sennae fructus angustifoliae 2. 200 kg lo ¦ Usual additives as above.

1 2 ¦ The parameters of this further preferred embodiment 13 ¦ are in the same range.

1 ~ 67~J69 1 ¦ The laxatlves of the invention are characterized by their 2 mild, reliable action combined with complete tolerability.
3 The compositions of the invention are also characteriæed by 4 stable effectivenss over long periods, no habituation phenomena having been observed.

7 To establish the pharmacological safety of the laxatives 8 of the invention, the embod:iment set forth in the above 9 preparation example was tested as follows:

ll Toxicity and Side EFfect Tests 13 Acute toxicity was tested in rats and mice of both sexes, 14 using 40 of each. The powdered material was suspended in water and the fresh suspension administered per os to the animals, 16 which were observed for eight days. The precise determination 17 of the LD50 proved to be impossible because the toxicity was 18 too low. Even one hundred times the daily dose recommended l9 for human beings produced no harmful effect.
LV50 (per os) in the rat: 5 g/k~;
21 in the mouse: 10 g/kg.

23 In additional tests for the subacute toxicity in rats 24 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.
26 To test for the chronic toxicity, a dose of 0.5 g/kg and 1.0 27 g/lcg was administered per os to two groups of rats (Sprague-28 Dawley) of 150 g body weight, of male and female sex.
: 29 Tests were made for weight gain, erythrocyte count, . ~- 16 -'~ ~

~ : 1~)7~69 1 leucocyte count, diEferential white count, blood sugar, 2 prothrombin time, transaminases and residual nitrogen before 3 and after treatment. I~o marked changes were observed in comparison with a control group of animals.
6 After the tests were completed, all of the animals were 7 killed and subjected to a complete autopsy. 'rhe weight of 8 the spleen, liver, heart, kidneys, brain, suprarenal gland, 9 thyroid gland, testes and hypophysis showed no Marked anomalies in comparison with the control animals. ~istologically, 11 virtually no changes were observed with regard to cellular 12 infiltration, fatty infiltration and adenomatose hyperplasia 13 of the liver, nephrosis, sinusoidal dilatation of the adrenals, 14 cellular infiltration of the heart, adenomatose hyperplasia of the thyroid, and infiltration of the cells of the spleen and 16 testes.

18 In another series of toxicity tests the subacute toxicity 19 of the composition of the invention,administered over thirty days, was investigated both in rats and dogs and in still 21 another series of safety tests chronic toxicity was determined 22 both in rats and do~s by administration over a period of 180 23 days. Oral administration of the inventive composition for 24 thirty consecutive days in doses five and ten times higher than those recommended for human consumption was well tolerated by 26 rats and dogs of both sexes. Oral administration of the com-27 position over a period of 180 days in doses two-and-a-half 28 and five times higher than those recommended for hurnan con-29 sumption was well tol~rated by prague-Dawley rats and mongrel dogs of both sexes. During and after the treatment there were .. . ,, ..

~167-l6~

1 no changes observed in the following parameters: development 2 of body weight, hematological, blood chemistry, and urino-3 logical parameters, macroscopic and microscopic examination of 4 the principal organs. In ~articular there was no incidence of bleeding or ulceration of the gastrointestinal tract.
7 Studies on the rabbit, with a daily administration of 8 1.0 g/kg for 6 weeks to male and female animals by adminis-9 tration per os, gave no inclication of any harmful effects as regards body weight, erythrocyte count, leucocyte count, 11 differential white count, residual nitrogen and blood sugar.

13 The teratogenic action oE the product was tested in 14 rats and rabbits with daily doses of 1 g/kg ~_ os, which were a~ministered Erom the 7th Eo 21st day of pregnancy in 16 the rat and from the 7th to the l5th day in the rabbit.
17 The fetuses were removed from the animals on the 21st and 27th 18 day, respectivel~, and examined. Ilo specific teratogenetic 19 effect of the product was found, and evidently the inventive composition has no effect on embryonic development.

22 Laxative Action Tests 24 For the testing of the laxative action itself, single doses of 2.5 and 5 g/kg were administered per os respectively 26 to mice `and rats. A decided increase and so:Etening of the 27 feces was observed. A definitely dose-related effect is 28 observed 3 to 4 hours after administration. The influence 29 of the product on intestinal motility and on the time 30 I required for the ssage of the ntest~nal contents .

1 ~6~69 1 was tested in rats (strain Sprague-Dawley) of both sexes 2 weighing 240 g, in groups of 10 animals each. After 2~ days 3 of fasting, the anima].s were administered per o.s 22 ml/kg of 4 aqueous suspension of 10~/a animal charcoal and 0.5% carboxy-methylcellulose, as well as 2.5 and 5 g/kg, respectively, o~
6 the product under test. Forty minutes after administration 7 the animals were killed and the total length of the small 8 intestine and the suspension-filled length of same were 9 measured. The following results were obtained:

11 Treatment Dose Intestinal l2 ~/kg Eill length ~ __ 13 _ _ 56 ~- 4.4 14 Laxative 2.5 79 + 6.2 Laxative 5 86 + 6.8 18 In another series of tests the laxative action of the 19 inventive composition was determined by administration of the test substance at different dosage levels to rnice and rats.

22 The test procedure was as follows:
23 An equal number of male and female mice (strain Swiss) 24 with a mean body weight of 24 g and the same number of male and fernale rats (strain Sprague-Dawley) with a mean body weight 26 of 230 g were used. After withdrawin~ food frorn the animals for 27 3 hours, they were housed in a compartmentalized cage. The 28 floor of the cage was covered with filter paper in order to 29 collect the fecal pellets of each animal. The animals which excreted soft fecal pellets were rejected from the ex?eriment.

-`` . ` ~ ~ 67~69 1 The remaining animals were placed i.n the treatment cage. The test composition was administered p.o. using an oral syringe at 3 2.5 and 5 g/kg. At regular time intervals, up to 8 hours 4 after the administration of the inventive composition, the number and nature of the fecal pellets excreted by each animal 6 was observed. The results are set forth in the tables below 7 (wherein "Test Comp" is the inventive composition):
8 Investi~ation of the laxative effect in the rat.
9 (single dose of 2.5 and 5.0 g/kg p.o.)
10 . _ _, ___ ~ _
11 n Treatment g/kg Observation period (no. of hours afer administration~
12 _ . ............. _ V ~ H S 6 8 10 controls _ 2.4 0.1 3.8 0.1 4.5 0.1 4.5 0.1 16 10 Test Col;p 2.5 3.1 0.2 3.~ 2.2 4.2 6.2 5.4 6.8 17 10 Test Comp 5 ~ ~ ~ 3.9 6.1 1 4.4 7.2 4.9 9 1 18 H = hard faeces: No. of faecal pellets per rat 19 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 e o ) _ . _~
23 n Treatment g/kg Observation periot (no. of hours after administratio~
24 H 2 `S L~ S ~ ~ ~ S A
_ _ _ ~ ~ __ 26 20 controls _ 3.1 0.1 4.2 0.1 4.4 0.2 4.~ 0.2 28 20 Test Co~ 2.5 2.4 0.2 4.2 201 5.1 3.3 5.3 3~8 29 20 Test C ~ 5 2.6 3,4 4.4 5.6 4.6 8.Z 4.6 9.8 I H = hard faeces: No. of faecal pellets per ncuse ¦ S = soft faeces: No. of faecal pellets per mouse I
~ ¦
~ 20 _ ~ ~7~16(3 Investiqation of the laxative effect in the rat.
1 (single dose o~ 2.5 and 5,0 g/kg p.o.) 4 n Treatment g/kg 6 . 2 Hours after administrati ~n 8 _. . _ . _. -. . ~ ~__ 710controls _ 0/10 0/10 Z/10 2/10 810Test Co~p 2.5 3/10 5/10 5/10 6/lD
910Test Ctmp 5 3/10 7/10 10/lD 10/lO
. .
11 With these animals obviously at a dosis above 2.5 g/kg the upper limit with regard to an increase of activity is reached.
12 Investi~ation of the laxative effect in the rat.
13 (single dose _f 2.5 an~ 5.0 g/kg p.o.)
14 _ _ _ _ .
n Treatment 9/~9 No. of mice with soft faeces/No. of treated animals 16 . Hours after admi~istration 18 ~ _ _ 19 20 controls _ . Ot2D 1/20 4/20 4/20 20 Tes~ CC~D 2.5 4/20 S/20 10/20 17/20 21 20 ~est Cbmp 5 8/20 17/2D ~ 20/20 Z0/20 23 The results showed a distinct laxative action dem-24 onstrated by the increased frequency of defecation and also by a substantial increase in soft fecal pellets in comparison 27 with hard fecal pellets.

2g 21 _ 1 ~ ~7'~69 1 In a test for diuresis, a recluction of kidney secretion 2 was observed, which appears to be connected with the increase 3 in the enteral fluid excretion. In a test for choleretic 4 action, virtually no significant change was detected, and from this it is concluded that the product of t'ne invention has no 6 choleretic action. The daily food intake was also teste~;
7 virtually no change was found.
The product administered per 09 in doses of 1.0 and 2.0 9 g/kg to male rats to 280 grams weight produced no perceptible changes in arterial blood pressure and heart rate. Also, no 11 inflammatory changes in the gastrointestinal area were detected.
12 In summary, the test results established that the in-13 ventive composition has very low toxicity, i.e., even too low to 14 determine the LD50 in the in vivo experiments in which the inventive composition was administered in dosa~es 100 times those 16 reco~ended for hu~an therapy. No toxic effects or intolerance 17 were observed, only laxative action, i.e., its main 18 pharmocological property. In addition, no inflammatory changes 19 in the gastric and intestinal regions of animals receiving one large dose of the composition or long-term treatment therewith 21 was established and this is regarded as surprising since in-22 flammatory changes are frequently observed in ani~aals treated 23 with laxatives. In gravid animals the administration or the 24 inventive composition did not evo~e any changes in normal feta].
development and the test animals were totally comparable to 2~ those of control animals with regard to number, weight and 27 appearance of the fetuses.
28 The laxative action of the invention composition was found 29 to occur between 3 and 4 hours after administration to the animals and was directly dosage related. The laxative action 1 ~ 67~6~

1 is accompanied by an acceleration o~ the transit time of contents 2 through the intestine. The diuresis experiments with treated 3 animals resulted in a diminution o:E urine output which can be 4 related to the increase in enteral fluid excretion. No changes in bile secretion, smooth muscle function, arterial blood 6 pressure or heart rate were demonstrated. Daily food intake 7 was also not affected by the administration of the inventive 8 composition.
~ 9 The laxatives of the invention are generally applied at 11 daily dosages of approximately 1 to 5 grams per 75 kg of 12 body weight to patients suffering from constipation and for 13 the regulation of the stool. The laxatives can be formulated 14 in a conventional manner with the addition of flavoring substances and the like. The addition of peppermit oil, 16 caraway oil and sage oil to sugar-coated preparations have 17 proven to be desirable in giving pleasantly administered 18 dragees.

21 When percentages are referred to hereinabove, percentage 22 by weight is intended, unless otherwise stated.

24 It will be understood that the specification a-nd ex-amples are illustrative but not limitative of the present 26 invention and that other embodimen-ts within the spirit and 27 scope of the invention will suggest themselves to those 28 skilled in the art.

~. .

.

Claims (42)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:
1. A method of preparing a laxative based on psyllium seeds and senna fruits, which method com-prises 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 a product having a residual moisture content of no more than 3.5% by weight of water and then coating the composition with a pharma-cologically acceptable material.
2. A method as claimed in claim 1 wherein said moistening with water is carried out using an amount of water which is from about 30 to 40% by weight, based on the moistened total mixture.
3. A method as claimed in claim 1 wherein said moistening is performed by continuously combining relatively small amounts of each grinding product mixture and water in a plurality of successive mixing stages.
4. A method as claimed in claim 3 wherein said mixing is caried out in a plurality of screw mixers.
5. A method as claimed in claim 1, 2 or 3 wherein said granulating step is performed in an extrusion press fitted with a separately controllable chopping knife at the press outlet.
6. A method as claimed in claim 1, 2 or 3 wherein said granulating step is performed at approximately 50 atmospheres of excess pressure and to result in particle sizes in the range of ap-proximately 2 to 2.5 mm.
7. A method as claimed in claim 1, 2 or 3 wherein said granules are dried in air in a fluidized bed for approximately half an hour.
8. A method as claimed in claim 1, 2 or 3 wherein psyllium seeds and senna fruits are initially ground separately to a grain size distribution of approximately:
99% finer than 500 um 85% finer than 400 um 50% finer than 200 um.
9. A method as claimed in claim 1, 2 or 3 wherein the ground psyllium seeds and senna fruits are mixed in a mixture ratio of about 4 : 1 to 5 : 1 (psyllium : senna).
10. A method as claimed in claim 1 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.
11. A method as claimed in claim 10 wherein the sennoside content of the senna fruits is adjusted to a standard value of 2.2% by weight.
12. A method as claimed in claim 1 wherein in the mixing step of the psyllium seeds and senna fruits there are additionally added psyllium husks and tragacanth gum.
13. A method as claimed in claim 12 wherein said supplementary husks are used in an amount of 3 to 4% and tragacanth gum in an amount of 1 to 1.5%, based on the total amount of ground psyllium seeds and senna fruits.
14. A method as claimed in claim 2 wherein said psyllium seeds and senna fruits are initially ground separately to a grain size distribution of approximately:

99% finer than 500 um 85% finer than 400 um 50% finer than 200 um and are mixed in a mixture ratio of about 4 : 1 to 5 : 1 (psyllium : senna).
15. A method as claimed in claim 14 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.
16. A method as claimed in claim 15 wherein in the mixing step of the psyllium seeds and senna fruits there are additionally added psyllium husks in an amount of 3 to 4% and tragacanth gum in an amount of 1 to 1.5%, based on the total amount of ground psyllium seeds and senna fruits.
17. A method as claimed in claim 14, 15 or 16 wherein said granulating step is performed at approximately 50 atmospheres of excess pressure and to result in particle sizes in the range of ap-proximately 2 to 2.5 mm., and said granules are dried in air in a fluidized bed.
18. A method as claimed in claim 1, 14 or 16 wherein the ground psyllium seeds and senna fruits are formed by grinding at a temperature not exceeding 80°C.
19. A method of preparing a laxative based on psyllium seeds and senna fruits, wherein said senna fruits are substantially enveloped by partially swollen psyllium seeds, comprising:
mixing separately ground psyllium seeds and senna fruits in a dry state, moistening the resulting mixture rapidly and uniformly with barely sufficient water, quickly granulating the resulting mixture, drying the granulated mixture in a manner preventing substantial swelling to a product having a residual moisture content of no more than 3.5% by weight of water, and coating the resulting combination com-prising said fruits substantially enveloped by partially swollen psyllium seeds with a pharmacolo-gically acceptable material.
20. A method as claimed in claim 19 wherein the ground psyllium seeds and senna fruits are mixed in a mixture ratio of about 4 : 1 to 5 : 1 (psyllium senna).
21. A method as claimed in claim 19 wherein said moistening with water is carried out using an amount of water which is from about 30 to 40% by weight, based on the moistened total mixture.
22. A method as claimed in claim 21 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.
23. A method as claimed in claim 22 wherein in the mixing step of the psyllium seeds and senna fruits there are additionally added psyllium husks and tragacanth gum.
24. A method as claimed in claim 23 wherein said supplementary husks are used in an amount of 3 to 4% and tragacanth gum in an amount of 1 to 1.5%, based on the total amount of ground psyllium seeds and senna fruits.
25. A laxative composition comprising ground psyllium seeds and senna fruits wherein said senna fruits are in a form substantially enveloped by swollen psyllium seeds.
26. A laxative composition as claimed in claim 25 additionally comprising supplementary psyllium husks and tragacanth gum.
27. A laxative composition according to claim 25 wherein the combination comprising said senna fruits enveloped by said psyllium seeds has a residual moisture content of no more than 3.5% by weight of water, said combination being coated with a pharmacologically acceptable material.
28. A laxative composition according to claim 26 wherein the combination comprising said senna fruits enveloped by said psyllium seeds has a residual moisture content of no more than 3.5% by weight of water, said combination being coated with a pharmacologically acceptable material.
29. A laxative composition as claimed in claim 25, 26 or 27 wherein the weight ratio of ground psyllium seeds to senna fruits is from 4 : 1 to 5 : 1.
30. A laxative composition as claimed in claim 28 wherein the weight ratio of ground psyllium seeds to senna fruits is from 4 : 1 to 5 : 1.
31. A laxative composition as claimed in claim 26 or 28 comprising approximately:
52% by weight psyllium seeds 12% by weight senna fruits 2% by weight supplementary psyllium husks 0.8% by weight tragacanth gum.
32. A laxative composition as claimed in claim 26 or 28 consisting essentially of the following:

Psyllium seeds ovatae 52.000 parts by weight Supplementary psyllium husks 2.200 parts by weight Sennae Fructus Angustifoliae 12.400 parts by weight Talcum 12.459 parts by weight Gum arabic 1.400 parts by weight Ferrum oxydatum, E 172 0.697 parts by weight Color Index (1956) 77492 Gum tragacanth 0.750 parts by weight 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 Saccharum 17.604 parts by weight per 100 parts by weight of composition.
33. A laxative composition as claimed in claim 26 or 28 consisting essentially of the following:
Psyllium seeds ovatae 54.200 parts by weight Sennae fructus angustifoliae 12.400 parts by weight Talcum 12.459 parts by weight Gum arabic 1.400 parts by weight Ferrum oxydatum, E 172 0.697 parts by weight Color Index (1956) 77492 Gum tragacanth 0.750 parts by weight 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 Saccharum 17.604 parts by weight per 100 parts by weight of composition.
34. A laxative composition based on psyllium seeds and senna fruits, wherein said senna fruits are substantially enveloped by partially swollen psyllium seeds, produced by a method comprising:
mixing separately ground psyllium seeds and senna fruits in a dry state, moistening the resulting mixture rapidly and uniformly with barely sufficient water, quickly granulating the resulting mixture, drying the granulated mixture in a manner preventing substantial swelling to a product having a residual moisture content of no more than 3.5%
by weight of water, and coating the resulting combination com-prising said senna fruits substantially enveloped by partially swollen psyllium seeds with a pharma-cologically acceptable material.
35. A laxative composition according to claim 34 wherein the weight ratio of ground psyllium seeds to senna fruits is from 4 : 1 to 5 : 1 and wherein said method comprises mixing said seeds and fruits in said ratio of from 4 : 1 to 5 : 1.
36. A laxative composition according to claim 34 wherein said moistening comprises moistening with an amount of water which is from about 3 to 4% by weight, based on the moistened total mixture.
37. A laxative composition according to claim 36 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.
38. A laxative composition according to claim 37 additionally comprising supplementary psyllium husks and tragacanth gum, said husks and gum have been added during said mixing.
39. A laxative composition according to claim 38 wherein said husks are added in an amount of 3 to 4% and said gum is added in an amount of 1 to 1.5%, based on the total amount of ground psyllium seeds and senna fruits.
40. A laxative composition comprising ground psyllium seeds and senna fruits in a weight ratio of ground psyllium seeds to senna fruits of from 4 : 1 to 5 : 1, said senna fruits being substantially enveloped by partially swollen psyllium seeds;
the combination comprising said senna fruits enveloped by partially swollen psyllium seeds having a residual moisture content of no more than 3.5% by weight of water and said combination being coated with a pharma-cologically acceptable material.
41. A laxative composition according to claim 40 wherein said combination additionally comprises psyllium husks and tragacanth gum.
42. A laxative composition according to claim 41 wherein said husks are present in an amount of 3 to 4% and said tragacanth gum is present in an amount of 1 to 1.5%, based on the total of ground psyllium seeds and senna fruits.
CA000368439A 1980-01-16 1981-01-13 Laxative composition comprising psyllium seeds and senna fruits and method for the preparation thereof Expired CA1167769A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP3001357.1 1980-01-16
DE3001357A DE3001357C2 (en) 1980-01-16 1980-01-16 Granulated laxative based on plantago seeds and senna pods and process for the manufacture of the same

Publications (1)

Publication Number Publication Date
CA1167769A true CA1167769A (en) 1984-05-22

Family

ID=6092153

Family Applications (1)

Application Number Title Priority Date Filing Date
CA000368439A Expired CA1167769A (en) 1980-01-16 1981-01-13 Laxative composition comprising psyllium seeds and senna fruits and method for the preparation thereof

Country Status (26)

Country Link
AR (1) AR222269A1 (en)
AT (1) AT372280B (en)
AU (1) AU547152B2 (en)
BE (1) BE887111A (en)
CA (1) CA1167769A (en)
CH (1) CH650403A5 (en)
CS (1) CS227324B2 (en)
DE (1) DE3001357C2 (en)
DK (1) DK153774C (en)
FI (1) FI75095C (en)
FR (1) FR2473311A1 (en)
GB (1) GB2067402B (en)
GR (1) GR73649B (en)
HK (1) HK75984A (en)
IE (1) IE50621B1 (en)
IT (1) IT1135052B (en)
LU (1) LU83058A1 (en)
MX (1) MX7112E (en)
NL (1) NL188452C (en)
NO (1) NO153594C (en)
NZ (1) NZ196034A (en)
PT (1) PT72358B (en)
SE (1) SE454744B (en)
SU (1) SU1145911A3 (en)
YU (1) YU42551B (en)
ZA (1) ZA81254B (en)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4321263A (en) * 1980-09-30 1982-03-23 Rowell Laboratories, Inc. Psyllium compositions
US5009916A (en) * 1983-12-12 1991-04-23 The Procter & Gamble Company Psyllium mucilloid fiber food products
EP0144644B1 (en) * 1983-12-12 1989-09-06 THE PROCTER & GAMBLE COMPANY Psyllium mucilloid products
US4950689A (en) * 1987-03-31 1990-08-21 Yang Robert K Pectin delivery system
DE69002561T2 (en) * 1989-08-10 1993-11-18 Procter & Gamble Agglomerated psyllium husk containing edible acid.
US5219570A (en) * 1989-08-10 1993-06-15 The Procter & Gamble Company Agglomerated psyllium husk containing edible acid
US5126150A (en) * 1990-10-01 1992-06-30 The Procter & Gamble Company Compositions containing psyllium
GB2272374B (en) * 1992-11-13 1996-07-03 Asta Medica Ag Stable senna extract formulations
FR2723318B1 (en) * 1994-08-04 1999-09-03 Chicouri Marcel NOVEL LAXATIVE COMPOSITIONS AND THEIR PREPARATION PROCESS
US20050053676A1 (en) * 2003-09-05 2005-03-10 Madaus Ag Powdered composition for use as laxative
ES2320827B1 (en) * 2006-12-29 2010-03-03 Madaus, S.A. "PHARMACEUTICAL COMPOSITION CONTAINING PSYLLIUM AND SENNA".
DE202007007143U1 (en) 2007-05-02 2008-06-12 Madaus Gmbh New pharmaceutical composition for use as a laxative
DE102007023397B4 (en) * 2007-05-02 2015-03-26 Madaus Gmbh New pharmaceutical composition for use as a laxative

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1847247A (en) * 1931-02-14 1932-03-01 Jones William Thomas Mechanical laxative
DE1003916B (en) * 1954-05-12 1957-03-07 Westminster Lab Ltd Process for the production of Sennespraeparaten
GB829068A (en) * 1958-04-09 1960-02-24 Mundipharma Ag Improvements in novel laxative agents
DE1103520B (en) * 1959-08-12 1961-03-30 Madaus & Co Dr Process for making a laxative
DE2629773C2 (en) * 1976-07-02 1985-06-27 Thiele, Henry, Dipl.-Ing. Dr., 7534 Birkenfeld Product made from bran and pectin

Also Published As

Publication number Publication date
IE50621B1 (en) 1986-05-28
SU1145911A3 (en) 1985-03-15
DE3001357A1 (en) 1981-07-23
AU547152B2 (en) 1985-10-10
YU42551B (en) 1988-10-31
MX7112E (en) 1987-06-29
DK15181A (en) 1981-07-17
GR73649B (en) 1984-03-26
AT372280B (en) 1983-09-26
PT72358A (en) 1981-02-01
FR2473311A1 (en) 1981-07-17
DK153774C (en) 1989-04-10
DK153774B (en) 1988-09-05
GB2067402B (en) 1984-01-25
NL188452C (en) 1992-07-01
NO153594B (en) 1986-01-13
GB2067402A (en) 1981-07-30
SE8100207L (en) 1981-07-17
IT1135052B (en) 1986-08-20
NZ196034A (en) 1984-05-31
FI75095C (en) 1988-05-09
AU6624181A (en) 1981-07-23
IT8119154A0 (en) 1981-01-15
DE3001357C2 (en) 1986-08-21
CH650403A5 (en) 1985-07-31
FR2473311B1 (en) 1984-03-30
PT72358B (en) 1981-12-18
HK75984A (en) 1984-10-12
ZA81254B (en) 1982-02-24
IE810074L (en) 1981-07-16
SE454744B (en) 1988-05-30
NL188452B (en) 1992-02-03
NO153594C (en) 1986-05-21
NL8100167A (en) 1981-08-17
NO810133L (en) 1981-07-17
CS227324B2 (en) 1984-04-16
FI75095B (en) 1988-01-29
AR222269A1 (en) 1981-04-30
LU83058A1 (en) 1981-06-04
BE887111A (en) 1981-07-16
ATA14681A (en) 1983-02-15
FI810095L (en) 1981-07-17
YU9581A (en) 1984-02-29

Similar Documents

Publication Publication Date Title
US4511561A (en) Laxative composition comprising psyllium seeds and senna fruits
CA1167769A (en) Laxative composition comprising psyllium seeds and senna fruits and method for the preparation thereof
CA1219770A (en) Dietary fibre product
CN103141709B (en) Carp feed and preparation method thereof
KR100255887B1 (en) Laxative composition containing lactic acid bacterium
CN104524110A (en) Traditional Chinese medicine composition with functions of tonifying spleen and clearing damp
KR100487732B1 (en) The method for manufacturing of feed
McCollister et al. Dietary feeding studies of methylcellulose and hydroxypropylmethylcellulose
CN106361741B (en) A kind of chlorophyll composition for being used to treat constipation
CN110721256B (en) Traditional Chinese medicine composition for preventing and treating teniasis of laying hens and preparation method thereof
WO2021074807A1 (en) Nutritional supplement
AU728928B2 (en) Anticancer drug
CN110100953A (en) A kind of pet fermented food and production technology
CN111437313A (en) Traditional Chinese medicine pill for relaxing bowel and preparation method thereof
GB2029217A (en) Herbal Bakery Products
JPS6026375B2 (en) A laxative made from pusillium and senna seeds
RU2185845C2 (en) Biologically active food additive "pochechnyye"
WO2002082928A1 (en) Health foods supplementary for treatment and prevention of constipation
US20110033563A1 (en) Stabilized Senna Extract Gel Formulation and Method of Preparation
CN115137787A (en) Intestine moistening and bowel relaxing aloe composition, aloe capsule and preparation method thereof
CN117838781A (en) Traditional Chinese medicine formula capable of burning fat and resisting hunger and losing weight and preparation process thereof
CN114681579A (en) Traditional Chinese medicine granules for treating calf new roundworm intestinal obstruction and preparation method thereof
Sari et al. The Potential of Polysaccharides from Various Plants as Constipation Treatment
CN116076745A (en) Method for extracting soluble dietary fiber by combining low-temperature vacuum microwave puffing and fermentation and dietary fiber defaecation and weight-losing composition
CN107439792A (en) A kind of fermented feed for preventing and treating milch goat stomatitis and preparation method thereof

Legal Events

Date Code Title Description
MKEX Expiry