NZ196034A - Laxative comprising ground psyllium seeds and ground senna fruits - Google Patents
Laxative comprising ground psyllium seeds and ground senna fruitsInfo
- Publication number
- NZ196034A NZ196034A NZ196034A NZ19603481A NZ196034A NZ 196034 A NZ196034 A NZ 196034A NZ 196034 A NZ196034 A NZ 196034A NZ 19603481 A NZ19603481 A NZ 19603481A NZ 196034 A NZ196034 A NZ 196034A
- Authority
- NZ
- New Zealand
- Prior art keywords
- weight
- parts
- psyllium
- ground
- seeds
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/481—Astragalus (milkvetch)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
- A61K36/482—Cassia, e.g. golden shower tree
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/534—Mentha (mint)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
- A61K36/537—Salvia (sage)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/68—Plantaginaceae (Plantain Family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
Description
New Zealand Paient Spedficaiion for Paient Number 1 96034
196034
Priority D_: ■<;: f;x"; /^ - 7^ 5?o "1
1 ' ' * * 1 1 * » • > « i * » , , , , ,
Compfcta Specification Filed* (|b •/• «/•
««* .9felS.fR/7?...;.. Patted J1 MAY19W"
' " ' r ' B
P.O.. Jc-arr.ra-Mo':- ' 1358
II ^ " f? $ j|Sj jl iH ^ i t.^ijt
L1^ JAN 1981
N.Z. NO.
NEW ZEALAND ■ Patents Act, 1953
COMPLETE SPECIFICATION
"LAXATIVE COMPOSITION COMPRISING PSYLLIUM SEED AND SENNA FRUITS."
We, DR. MADAUS & CO., a German company of 5 Koln-Merheim,, Federal Republic of Germany do hereby declare the invention, for which we P^ay that a Patent may be granted to us , and the method by which it is to be performed, to be particularly described in and by the following statement:-
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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 (Planta^o 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 angustifolia) 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 pharmacological 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 oxidized to the rhein, which has a certain convulsant and pain producing action. There has thus been a need for a composition which overcomes or mitigates the possibility of un^
desirable side effects. •
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The 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 psyllium seed (I) and senna fruits (II) and is characterized in that Component II is in a form in which it is largely enveloped by dried-on component I.
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.
This protective action may additionally be stabilized and enhanced if the mixture of the two ground components psyllium seeds ovatae and sennae fructus angustifoliae is additioned with minor proportions of 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 swell-
r mucinous ing ability by virtue of the ' products contained therein in a substantially higher concentration. Measures of the swelling number according to West German Pha33i\acopoeia 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.
frl.Z. PATENT OFFICE
. 3 . 15 DEC 1983
RECEIVED
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196034
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 despersed sennae fructus particles which is particularly advantageous for a pharmaceutical application.
The weight ratio of the psyllium seed portion to the sennae fruit portion in the laxative composition according to the 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 advantageous.
As now recognized psyllium seed not only contains a considerable amount of material insoluble in water, but also forms an insoluble hydrolysis residue of about 3o-35 % This, togehter with a neutralizing action of certain components of psyllium seed, seems to be the reason for the favorable characteristics of the new compositions comprising comminuted senna fruits prevailingly enveloped by a protective psyllium seed coating.
To make such preparations, separately ground psyllium seeds and senna fruits are mixed together dry, and the
/between substantially 30 mixture, rapidly and uniformly moistened with * and 5o %
rby weight water/, is so quickly granulated and dried that substantial swelling of the product is suppressed, and the granules, dried to a residula moisture content of no more than 3.5 %, are then feuga^"coatedy
* N.2. PA ]
2 5 JAN 1984
RECEiVEr J
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196034
According to a preferred embodiment the ground psyllium seeds and senna fruits are kneaded with 3o to
4o % 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 r mucinous
I 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 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.
Prior to the grinding the psyllium seeds and senna fruits are conveniently dried to a moisture content of 3.5 % at a temperature of 80° C and the sennoside content of the senna fruit componente is adjusted at 2.0 to 2.5 % by weight, preferably at approximately 2.2 % by weight by combining different lots. During the grinding operation the temperature of the ground material should not exceed 8o° C.
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
N.2, PATE,\TOFF5CE
2 5 JAN 1984
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196034
(water) becomes a mucilage resulting in an enveloping of the sensitive senna fruit component.
It has been found that when proceeding in accordance with the process of the invention, there occurs a favorable and beneficial pH adjustment, the effect of which is that an initially acid pH (e.g., pH 5.5-6.0) is shifted toward the neutral point, i.e., pH 7.0, by 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 the process of the invention leads to an inherently pH neutral product, the stability thereof is desirably enhanced.
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 continous matter) and subjected to intensive mixing in a series of mixing operations. Preferably this is accomplished in a plurality of sequential screw blenders.
In this manner, a uniform paste is produced within a few minutes and the material is deliverd to the granulator which must also be a fast-operating machine. Preferably, therefore, an extrusion press having a large D ratio, at whose output a separately driven, revolving chopper provides for immediate chopping of the emerging strand into pin length granules of sizes ranging around 2 to 2.5 mml, is used.
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The granulated material is preferably dried in a fluidized bed using air, in which a rapid, gentle drying is achieved, and caking of material is prevented. We found that the granulated material, of which only the fines are swollen with moisture, undergoes this process without appreciable shrinkage and can be delivered in the resultant form to the final, sugar-coated operation.
Preferably, psyllium husks (especially in an amount compensating for psyllium husk portions possibly lost during the comminution of the psyllium seed) and tragacanth gum are 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 admixture of the ground psyllium seeds and senna fruits range 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 tragacanth gum are added, preferably 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 fruits.
Psyllium seeds and senna fruits are ground separately to approximately the same grain size distribution, preferably to approximately the following sieve analysis:
99 % finer than 500 jum diameter 85 % finer than 4oo ;um diameter 5o % finer than 2oo jura diameter
N.Z. PATENT OFFICE
DEC 1983
RECEIVED
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1 96034
An especially preferred laxative contains especially about 75 % psyllium seed, approximately 2o % senna fruits, approximately 3.2 % additional psyllium husks, and about o.8 % gum tragacanth.
A particularly preferred embodiment of the above described product consists essentially of the following:
Psyllium ovatae seeds 52.ooo parts by weight
Psyllium ovatae seeds (husks) 2.2oo sennae fructus angustifoliae 12-4oo talcum 12.459
gum arabic 1-4oo ferric oxide - E 172 o.697 Color Index (1956) 77 492
77 499 77 491
gum tragacanth o.75o oleum-carvi o.o35
oleum salviae (the essential o-o35
oil of Salvia officinalis)
oleum menthae piperitae o.ojo paraffinum subliquidum o. 24o paraffinum durum o. '11<0
saccharum 17;6o4
per loo parts by weight of composition.
A further particularly preferred embodiment comprises the following components:
; Psyllium ovatae seeds 54. 2oo parts by weight sennae fructus angustifoliae 12.4oo usual additives, as described above.
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During the overall preparation a control of the bacteria number should be continously 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 mucuous 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 ^mucinous dried-om 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° C) using 12'. 4 g of ground sennae fructus angustifoliae rmere ad-
(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).
N.Z. PATENT OF" S ~-r ~!
2 5 JAN 1984
Dcr>~-
196034
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The above ground products were stirred in 3oo ml extraction liquid each for 1o and 3o minutes, respectively. The liquid was separated from the insolubles by centrifuging and lyophilized. 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 lots 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
1o min 3o min 1o min 3o min 1o min 3o rain
I
85. 2 %
88.9 %
55. 6
%
59. 3
%
74/1
%
74.1
%
II
55.6 %
59 .3 %
4o. 7
%
44. 4
%
48.2
%
59- 3
%
III
13 .o %
8.9 %
6.7
%
2.2
%
3. 2
%
. 6
%
These data clearly show a retarded release of the sennosides for the laxative composition according to the invention.
The retarded release of the sennosides fronj. the laxative composition according to the invention does not result in a complete blocking of the active ingredients, which, to the contrary are substantially completely released over longer periods of time as evidenced by the following in vitro test:
I H?»:TOFFICE
-lo -
DEC 1983
RECEIVED
196034
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The laxative composition of the invention was allowed to swell overnight. Thereafter the swollen material was additioned with water and extracted five times with the water phase being renewed after each hour. After five hours extraction approximately 8A % 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 (g9
dissolved Sennoside portion (%)
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2o.73
o. 126
A6. 67
2.
6.56
o.o51
18. 89
3.
2-98
o. o26
9. 63
A.
1.53
o^ ol A
CO i_n
.
1.15
o. oo9
3. 33
Total
o. 226
83. 7
Upon using artificial gastric juices and artificial bowel juices, respectively, essentially the same data are obtained.
The above tests, which are approximated to the mean duration of residence of the drugs in the gastro-intestinal tract clearly show that essentially all of the Sennosides of the sennae fruit component in the laxative composition
DEC 1983
RECEIVED
196034
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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 characterized by a particularly high tolerability, particularly as an aid to defecation 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.
PREPARATION EXAMPLE
Psyllium seeds were cleaned of dirt and foreign seeds, dried at about 8o° C to a moisture content of 3.5 %, and ground to a grain size distribution corresponding to the following sieve analysis
99 % finer than 5oo um 85 % finer than Aoo um 5o % finer than 2oo um.
In the grinding process the material must not be heated above 8o° C.
Senna follicles were tested separately for their sennoside content and standardized at 2.2 % by the mixing of different lots, if necessary. The grinding of this material to a size corresponding to the size specified above for psyllium seeds was performed in
IV.,1 PA'i'c IV r OrFfCii
1S D E C1983
RECEIVr)
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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: 1o5.5oo kg senna fruits: 27.600 kg husks and gum: 5.9oo kg
138.ooo kg
This pre-granulate resulted, after the below-described granulation and dragee formation procedure, in 2oo kg of final laxative product.
The powder mixture passed.from the mixing vessel to the mixing section feeding the strand extruder, in which approximately 3o-4o % 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 5o atmospheres excess pressure and 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 a moisture content of 35 %.
The drying operation that follows was performed in a fluidized bed dryer with vibratory feed, to a residual xhaif Ap hour (eg within 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 meters per hour.
• -Z. PATENT OFFICE
DEC 1983 received
1 96034
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The dry granules were sifted to remove those smaller than 1 mm and those over 3 mm, and then their, buld weight was from 51o to 53o grams per liter. Finally the material was formulated into dragees by contacting the above "pre-granulate" with a dragee suspension comprising aromatic essencesgum arabic, saccharose pigment and talcum which was applied to the pre-granulate in a conventional dragged— making machine. This resulted in a sugar-coated dragee incorporating therein a flavoring mixture of peppermint oil, caraway oil and sage oil (ratio 2:1:1) in amounts of approx o.1 % with respect to the final product. The bacteria count cf the material was constantly inspected durirg the entire process.
The final product, which is the particularly preferred embodiment of the invention because of its outstanding pharmacological properties,, had the following composition
(per loo kilograms of product): .
Psyllium seeds ovatae 52.ooo kg
Supplementary Psyllium husks 2.2oo kg Sennae fructus angustifoliae 12.4oo kg
Talcum Gum arabic
Ferrum oxydatum, E 172
Color Index (1956) 77492
77499 77491
Gum tragacanth
Oleum carvi
Oleum salviae
Oleum menthae piperitae
Paraffinum subliquidum
Paraffinum durum
Saccharum
12.459 kg 1.4oo kg o.697 kg o.75o kg o.o35 kg o.o35 kg o.ojo kg o.24o kg o.11o kg
17.6o4 kg
The above product has a swelling number of about 7. 5o (at leat 6.o) (determined according to West German Pharma-kopoea DAB 8), a bulk density of o.765 to 0.905 g/ral
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(determined according to DIN 53 912), a granula diameter of 1 to 3 mm and a sennoside content of o, 25 % to o,31 % particularly of o,27 %. These parameters ensure a particu larly good overall action.
A further preferred embodiment consists of the following:
Psyllium seeds ovatae, ground product 54.2oo.kg
Sennae fructus angustifoliae • 2.2oo kg
Usual additives as above.
The parameters of this further preferred embodiment are in the same range.
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The laxatives of the invention are characterized by their mild, reliable action combined with complete tolerability. The compositions of the invention are also characterized by stable effectivenss 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 preparation 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 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.
LD^q (per os) in the rat: 5 g/kg;
in the mouse: 10 g/kg.
In additional tests for the subacute toxicity in rats and micQ, 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 per 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,
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leucocyte count, differential white count, blood sugar, prothrombin time, transaminases and residual nitrogen before and after treatment. Ho marked changes were observed in comparison with a control group of animals.
After the tests were completed, all of the 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. Histologically, virtually no changes were observed with regard to cellular infiltration, fatty infiltration and adenomatose hyperplasia of the liver, nephrosis, sinusoidal dilatation of the adrenals, cellular infiltration of the heart, adenomatose hyperplasia of the thyroid, and infiltration of the cells of the spleen and tcstes .
In another series of toxicity tests the subacute toxicity of the composition of the invention, administered over thirty days, was investigated" both in rats an'd dogs and in still another series of safety tests chronic toxicity was determined both in rats and dogs by administration over a period of 180 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 prague-Dawley rats and mongrel dogs of bo'th sexes. During and after the treatment there were
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ho changes observed in the following parameters: development of body weight, hematological, blood chemistry, and urino-logical 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, leucocyte 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 t 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 fetuses were removed from the animals on the 21st and 27th day, respectively, and examined. Wo 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 feces 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
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was tested in rats (strain Sprague-Dawley) of both sexes weighing 240 g, in groups of 10 animals each. After 24 days of fasting, the animals were administered per os 22 ml/kg of aqueous suspension of 107<> animal charcoal and 0.5% carboxy-methylcellulose, 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 Intestinal g/kg fill length (cm) ..
Laxative 2.5
Laxative 5
In another series of tests the laxative action of the inventive composition was determined by a omitiis tration 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 sane 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 compartmentalized cage. The floor of the cage was covered with filter paper in order to collect the fecal pellets of each animal. The animals which excreted soft fecal pellets were rejected from the experiment.
56 + 4.4 79 + 6.2 86 +6.8
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The remaining animals were placed in the treatment cage. The test composition was administered p.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 fecal pellets excreted by each 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. •
(single dose of 2.5 and 5.0'g/kg p.o.)
n
Treatment g/kg
Observation period (no.
of hours afer administration)
Z
4
6
8
H S
H S
H S
H S
controls
- -
2.4 0.1
3.8 0.1
4.5 • 0,1
4.5 0.1
Test Coirp
2.5
3.1 ' 0.2
3.8 2.2
4.2 6.2
.4 6.8
Test Comp
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 g/kg
Observation period (no.
of hours after adnri ni stratioi
2
4
.6
8
H S
H • S
H S
H S
controls
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' 3.1 0.1
4.2 ' 0.1
4.4 0.2
4.5 0.2
Test Corp
2.5
2.4 0.2
4.2 2.1
.1 3.3
.3 3.8
Test Conp
•
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 S = soft faeces: No. of faecal pellets per mouse
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Investication 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"
controls
-
0/10
0/10
2/10
2/10
Test Conp
2.5
3/10
/10 •
/10
6/10
Test Coivp
3/10
7/10
/10
/10
With these animals obviously at a dosis above 2.5'g/kg the upper limit with■ regarc' to an increase of activity is reached.
Investigation of the laxative effect in the rat.
(single dose of 2.5 and '5.0 g/kg p.o.)
n
Treatment gAs
No. of mice with soft faeces/No. of treated animals
Hours after administration
2
'4
•5
8
controls
- •
0/20
1/20
4/20 -
4/20
Test Coid
2.5 .
4/20
3/20
/20
17/20
i
Test Comp
'
8/20
17/20 ,
/20 '
/20
The results showed a distinct laxative action demonstrated by the increased frequency of defecation and also-by a substantial.increase in soft fecal pellets, in comparison with hard fecal pellets.
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In 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 chang'e was found.
The product administered per os in doses of 1.0 and.2.0 g/kg to male rats to 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 the inventive composition has very low toxicity, i.e., even too low to determine the LDrn in the in vivo experiments in which the 50
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 pharmocological property. In addition, no inflammatory changes in the gastric and intestinal regions of animals receiving one large dose of the composition or long-term 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 fetal development and the test animals were totally comparable to those of control animals with regard to number, weight and appearance of the fetuses. "
The laxative action of the invention composition was found to occur between 3 and 4 hours after administration to the animals and was directly dosage related. The laxative action'
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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 inventive, composition.
The laxatives of the invention are generally applied at 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 flavoring substances and the like. The addition of peppermit oil,
caraway oil and sage oil to sugar-coated preparations have proven to be desirable in giving pleasantly administered dragees. -
When percentages are referred to hereinabove, percentage by weight is intended, unless otherwise stated.
It will be understood that' the specification and examples are illustrative but not limitative of the present invention and that other embodiments within the spirit and scope of the invention will suggest themselves to those skilled in the art.
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196034
Claims (3)
- WHAT WE CLAIM IS: 1. Method of preparing a laxative based on psyllium seeds and senna fruits, which method comprises mixing separately-ground psyllium seeds and senna fruit Ln a dry state, moistening the resulting ground mixture rapidly anc uniformly with between substantially 30 and 50% water by weight, uickly granulating the resulting mixture and drying the ame in a manner preventing substantial swelling to a roduct having a residual moisture content of no more optionally han 3.5% by weight of water and thenj coating the omposition with a pharmacologically acceptable aterial.
- 2. Method as claimed in claim 1 wherein said moistening with water is carried out using an amount of water which is from 3o to Ao % by weight, based on the moistened total mixture.
- 3. Method as claimed in claim 1 wherein said moistening is performed by continuously combining relatively small amounts of the. grinding product mixture and water in a plurality of successive mixing stages. A. Method as claimed in claim 3 wherein said mixing is carried out in a plurality of screw mixers. 5. Method as claimed in claim 1 wherein said granulating step is performed in an extrusion press fitted with a separately controllable chopping knife at the press outlet. - 2A - N.Z. PA." " 2 5 JAN REr 1 2 3 4 5 6 7 8 9 1 o 11 12 13 14 15 16 17 18 19 2o 21 22 23 24 25 26 27 28 29 3o I 96034 6. Method as claimed in claim 1 wherein said granulating step is performed at substantially . 50 atmospheres of excess pressure and to result in particle sizes in the range of 2 to 2.5 mm in length. 7. Method as claimed in claim 1 wherein said granules are dried in air in a fluidized bed for substantially haif an hour. 8. Method as claimed in claim 1 wherein psyllium seeds and senna fruits are initially ground separately to a grain size distribution of substantially 99 % finer than 5oodiameter 85 % finer than 4oo yum diameter 5o % finer than 2ooyUm diameter. 9. Method as claimed in claim 1 wherein the ground psyllium seeds and senna fruits are mixed in a r- by weight mixture ratio of - 4 : 1 to 5 : ij(psyllium : senna). 10. 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. Method as claimed in claim 1o wherein the sennoside content of the senna fruits is adjusted to a standard value of 2.2 % by weight. N.Z. PATEMT OFFICE - 25 - 25 JA^ 1 2 3 4 5 6 7 8 9 1o 11 12 13 14 15 16 17 18 19 2o 21 22 23 24 25 26 27 28 29 3o rl . j , 12. Method as claimed in.claim 1 whereinIthe mixing step of the psyllium seeds and senna fruits there are additionally added psyllium husks and tragacanth gum. 13. 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. Laxative composition comprising ground psyllium seeds and senna fruits wherein said senna fruit is in a form substantially enveloped by swollen psyllium seeds. 15. Laxative composition as claimed in claim 14 additionally comprising supplementary psyllium husks and tragacanth gum. 16. Laxative composition as claimed in claim 14 wherein the weight ratio of ground psyllium seeds to senna fruits is from 4 : 1 to 5 : 1. 18. Laxative composition as claimed in claim 14 consisting essentially of the following: 17. Laxative composition as claimed in claim 14 comprising substantially 52 % by weight psyllium seeds 12 % by weight senna fruits 2 % by weight supplementary psyllium husks o.8 % by weight tragacanth gum. Psyllium ovatae seeds 52.ooo parts by weight Supplementary psyllium husks 2.2oo parts by weight Sennae Fructus Angustifoliae12.4oo parts by weight Talcum Gum arabic 12.459 parts by weight 1.4oo parts by weight _ _ 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 \7 18 19 20 21 22 23 24 25 26 27 28 29 30 \9 603A Ferric oxide, Color Index E 172 (1956) 77492 77499 77491 0.697 parts by weight Gum tragacanth °. 750 Oleum carvi o o35 Oleum salviae 0* o35 Oleum menthae piperitae o. o7o Paraffinum subliquidum O. 24o Paraffinum durum 0. 1 10 Saccharum 17. 6o4 parts parts parts parts parts parts parts by weight by weight by weight by weight by weight by weight by weight per 1oo parts by weight of composition. 19. Laxative composition as claimed in claim 14 consisting essentially of the following: Psyllium ovatae seeds 54 2oo parts by weight Sennae fructus angustifoliae 12 4o o parts by weight Talcum 12 .459 parts by weight Guip. arabic, . 1 ,4oo parts by weight Ferric oxide , E 172 o .697 parts by weight Color Index (1956) 77492 77499 77491 Gum tragacanth Oleum carvi Oleum salvias Oleum menthae piperitae Paraffinum subliquidum Paraffinum durum Saccharum o--75o parts o.o35 parts o.o35 parts 0-070 parts o«24o parts o.11o parts 17.6o4 parts by weight by weight by weight by weight by weight by weight by weight per 1oo parts by weight of composition. 20. A method according to Claim 1 substantially as hereinbefore described. - 27 - DR. MADAUS & CO., By Their Attorneys HENRY HUGHES LIMITED jj^PATENT OFFICE 15DECJ983
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
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 |
---|---|
NZ196034A true NZ196034A (en) | 1984-05-31 |
Family
ID=6092153
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NZ196034A NZ196034A (en) | 1980-01-16 | 1981-01-16 | Laxative comprising ground psyllium seeds and ground senna fruits |
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)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4321263A (en) * | 1980-09-30 | 1982-03-23 | Rowell Laboratories, Inc. | Psyllium compositions |
EP0144644B1 (en) * | 1983-12-12 | 1989-09-06 | THE PROCTER & GAMBLE COMPANY | Psyllium mucilloid products |
US5009916A (en) * | 1983-12-12 | 1991-04-23 | The Procter & Gamble Company | Psyllium mucilloid fiber food products |
US4950689A (en) * | 1987-03-31 | 1990-08-21 | Yang Robert K | Pectin delivery system |
US5219570A (en) * | 1989-08-10 | 1993-06-15 | The Procter & Gamble Company | Agglomerated psyllium husk containing edible acid |
DE69002561T2 (en) * | 1989-08-10 | 1993-11-18 | Procter & Gamble | 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)
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 |
-
1980
- 1980-01-16 DE DE3001357A patent/DE3001357C2/en not_active Expired
-
1981
- 1981-01-13 CA CA000368439A patent/CA1167769A/en not_active Expired
- 1981-01-14 GB GB8101047A patent/GB2067402B/en not_active Expired
- 1981-01-14 DK DK015181A patent/DK153774C/en not_active IP Right Cessation
- 1981-01-14 FI FI810095A patent/FI75095C/en not_active IP Right Cessation
- 1981-01-14 LU LU83058A patent/LU83058A1/en unknown
- 1981-01-15 IE IE74/81A patent/IE50621B1/en not_active IP Right Cessation
- 1981-01-15 NO NO810133A patent/NO153594C/en unknown
- 1981-01-15 ZA ZA00810254A patent/ZA81254B/en unknown
- 1981-01-15 AU AU66241/81A patent/AU547152B2/en not_active Ceased
- 1981-01-15 SE SE8100207A patent/SE454744B/en not_active IP Right Cessation
- 1981-01-15 CS CS81297A patent/CS227324B2/en unknown
- 1981-01-15 GR GR63874A patent/GR73649B/el unknown
- 1981-01-15 NL NLAANVRAGE8100167,A patent/NL188452C/en not_active IP Right Cessation
- 1981-01-15 CH CH247/81A patent/CH650403A5/en not_active IP Right Cessation
- 1981-01-15 IT IT19154/81A patent/IT1135052B/en active
- 1981-01-15 PT PT72358A patent/PT72358B/en not_active IP Right Cessation
- 1981-01-15 AT AT0014681A patent/AT372280B/en not_active IP Right Cessation
- 1981-01-16 AR AR283983A patent/AR222269A1/en active
- 1981-01-16 SU SU813238931A patent/SU1145911A3/en active
- 1981-01-16 YU YU95/81A patent/YU42551B/en unknown
- 1981-01-16 BE BE0/203510A patent/BE887111A/en not_active IP Right Cessation
- 1981-01-16 MX MX819267U patent/MX7112E/en unknown
- 1981-01-16 FR FR8100819A patent/FR2473311A1/en active Granted
- 1981-01-16 NZ NZ196034A patent/NZ196034A/en unknown
-
1984
- 1984-10-04 HK HK759/84A patent/HK75984A/en not_active IP Right Cessation
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