FORM 2
THE PATENTS ACT 1970
As amended by the Patents (Amendment) Act, 2002
COMPLETE SPECIFICATION
(See Section 10; Rule 13)
TITLE
Process for the preparation of a synthetic bulk laxative
APPLICANTS
KOPRAN RESEARCH LABORATORIES LIMITED,
Parijat House, 1076 Dr. E. Moses Road, Worli, Mumbai 400 018, Maharashtra, India, an Indian Company
The following specification particularly describes the nature of this invention and the manner in which it is to be performed

FIELD OF INVENTION
This invention relates to a process for the preparation of a synthetic
bulk laxative and a formulation comprising the same.
BACKGROUND ART
Laxatives are classified depending on their mechanisms of action. For example, laxative comprising preparations of sodium phosphate or magnesium sulfate are of the osmotic type. Laxative comprising preparations of phenolphthalein, bisacodyl, danthron, senna or cascara are of stimulant type and laxative comprising preparations of docusates, poloxamer, mineral oil or castor oil are of surfactant type. The osmotic, stimulant and surfactant laxatives have limited use due to non acceptable organoleptic properties and poor efficacy.
Yet another type of laxative is bulk laxative which on oral administration swells significantly occupying most of the intestinal lumen, thereby improving gastrointestinal motility to cure constipation. Bulk laxative is also used in the treatment of diarrhoea. Bulk laxative may comprise semisynthetic polymers such as calcium polycarbophil or methyl cellulose or natural products such as bran, psyllium or isphagula husk. Due to the low swellability of calcium polycarbophil ie calcium substituted polymer formed of acrylic acid monomer and a
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cross linker under physiological conditions, it is required to be prescribed in high doses of 4 - 6 g/day (i.e. 8-12 tablets of 500 mg/day). Methyl cellulose also has limited use due to its high dosage requirement (6 gm/day). Amongst the bulk laxatives, isphagula husk is most widely used. It exhibits low swelling (~ 40 times) in stimulated intestinal fluid (USP 23 Page No 2053) and necessitates administration of large doses (7 gm/day) which causes discomfort and results in loss of appetite. Besides swelling in the intestine, isphagula husk also significantly swells in the stomach occupying a large volume and causes abdominal pain and discomfort. Proteins associated with the natural product isphagula husk are known to cause sensitization of the mucous membrane, irritation and other allergic reactions in the body. Isphagula husk has low dispersibility in water because of which it forms lumps or agglomerates in aqueous fluids. The lumps swell non-uniformly and adversely affect gastrointestinal motility. Moreover, being a natural product, isphagula husk is prone to microbial contamination during storage.
US Patent No 4777232 describes such polymers comprising water soluble monomers such as acrylic acid or methacrylic acid and a polysaccharide such as starch or derivative
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thereof. It is formed in combination with a surface active agent and
employs the polysaccharide in an amount of 10- 70% by weight of
the monomer. US Patent No 3997484 discloses a graft polymer
formed of polyacrylonitrile and gelatinized starch such as
polysaccharide. Graft polymers of acrylic monomers such as
acrylonitrile with polysaccharide such as starch or cellulose derivative
are known (US Patents Nos 4076663, 4931497 and 5011892). US
Patent No 5340853 describes a mixture of 20 - 98%, preferably 10
- 50% by weight of a polymer such as polyacrylic acid,
polymethacrylic acid, polyacrylamide or polymethacrylamide and 2 -
80%, preferably 10-50% by weight of a polysaccharide such as
tragacanth or guar gum, gum arabic, starch, dextran, cellulose or
derivative thereof. Polymers comprising polysaccharides are
reported to find applications in diapers, sanitary napkins, tampons, surgical pads and sheets, paper towels, electrolyte thickeners in dry batteries, moisture conserving materials in agriculture or drying agents. The polymers of the above US Patents are not known or reported to have been used as laxative. Due to gelatinisation of starch, the polymers will show low swellability (30 to 40 times) in physiological fluids though their swellability in water is high. The starch in such graft polymers is likely to undergo digestion in the physiological fluid and reduce the swellability of the graft polymers.
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Moreover such polymers are not slimy. High percentages of polysaccharides in polymer have been found to reduce the swellability thereof in physiological fluids.
Crosslinked, water soluble, water absorbable or water swellable polymers formed of monomers such as acrylates, acrylic acids, acrylamides, acrylonitriles or vinyl pyrrolidones and cross linkers are known and reported to be used as absorbing or dehydrating or thickening agents in sanitary napkins, diapers, shaving system or for bioadhesion (US Patents Nos 5985944,4070348, 5354290, 5716707, 5804605,4618631,5514754, 5626154,4535098, 5973014, 5221722 and 4267103; EP Patent No. 105634B1 and JP Patent No. 6322178A).
Gums such as tragacanth, acacia or xanthan gum are water swellable and are known to be used as emulsifiers, binders, stabilizers, thickening or suspending agents in food and pharmaceutical industry.
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Disclosure of the invention
An object of the invention is to provide a synthetic bulk laxative, which shows high swelling in the physiological fluids and is slimy and assists bowel movement.
Another object of the invention is to provide a synthetic bulk laxative, which has less swelling in stomach than in the intestine and eliminates abdominal pain and discomfort.
Another object of the invention is to provide a synthetic bulk laxative, which may be administered in low doses of 1-2 gm/day.
Another object of the invention is to provide a synthetic bulk laxative, which does not cause mucous membrane sensitization, irritation or other allergic reactions.
Another object of the invention is to provide a synthetic bulk laxative, which does not form lumps or agglomerates and swells uniformly.
Another object of the invention is to provide a synthetic bulk laxative, which is non-absorbable in the intestinal fluid.
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Another object of the invention is to provide a synthetic bulk laxative, which is inert and non-susceptible to microbial contamination during storage.
Another object of the invention is to provide a process for the preparation of a synthetic bulk laxative, which results in a product having high swelling in the physiological fluids and is slimy to assist bowel movement.
Another object of the invention is to provide a process for the preparation of a synthetic bulk laxative, which results in a product having less swelling in stomach than in the intestine and thus eliminating abdominal pain and discomfort.
Another object of the invention is to provide a process for the preparation of a synthetic bulk laxative, which results in a product that may be administered in low doses of 1 - 2 gm/day.
Another object of the invention is to provide a process for the preparation of a synthetic bulk laxative, which results in a product
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that does not cause mucous membrane sensitization, irritation or other allergic reactions.
Another object of the invention is to provide a process for the preparation of a synthetic bulk laxative, which results in a product that does not form lumps or agglomerates and swells uniformly.
Another object of the invention is to provide a process for the preparation of a synthetic bulk laxative, which results in a product that is non-absorbable in the intestinal fluid.
Another object of the invention is to provide a process for the preparation of a synthetic bulk laxative, which results in an inert product non-suspectible to microbial contamination during storage.
Another object ofthe invention is to provide a method of making a formulation of a synthetic bulk laxative, which has high swelling in the physiological fluid and is slimy to assists bowel movement.
Another object of the invention is to provide a method of making a formulation of a synthetic bulk laxative, which has less swelling in
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stomach than in the intestine and eliminating abdominal paid and discomfort.
Another object of the invention is to provide a method of making a formulation of a synthetic bulk laxative, which may be administered in low doses of 1 - 2 gm/day.
Another object of the invention is to provide a method of making a formulation of a synthetic bulk laxative, which does not cause mucous membrane sensitization, irritation or other allergic reactions.
Another object of the invention is to provide a method of making a formulation of a synthetic bulk laxative, which does not form lumps or agglomerates and swells uniformly.
Another object of the invention is to provide a method of making a formulation of a synthetic bulk laxative, which is non-absorbable in the intestinal fluid.
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Another object of the invention is to provide a method of making a formulation of a synthetic bulk laxative, which is inert and non-suspectible to microbial contamination during storage.
According to the invention there is provided a synthetic bulk laxative comprising a crosslinked graft polymer formed of a hydrophilic monomer partially neutralized from 20% - 75%, a polysaccharide gum from 0.05%-3% by weight and a crosslinker from 0.01%- 2% by weight; the weight percentages being with respect to the hydrophilic monomer.
According to the invention there is also provided a process for the preparation of a synthetic bulk laxative comprising:
a) 20%- 75%o partial neutralization of a hydrophilic
monomer with an alkali;
b) polymerization of the partially neutralised
hydrophilic monomer with 0.01 - 2% by weight of a cross linker
and 0.05%- 3% by weight of a polysaccharide gum in the presence
of an initiator in an organic solvent under inert atmosphere at 30 -
80 ° C, the weight percentages being with respect to the hydrophilic
monomer;
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c) drying the synthetic bulk laxative at 30-120°C; and
d) pulverizing the dried synthetic bulk laxative.
According to the invention there is also a method of making a formulation of a synthetic bulk laxative comprising mixing a crosslinked graft polymer formed of a hydrophilic monomer partially neutralized from 20% - 75%, a polysaccharide gum from 0.05% - 3% by weight and a crosslinker from 0.01%-2% by weight, the weight percentages being with respect to the hydrophilic monomer, mixed with pharmaceutically acceptable excipients.
Preferably the polysaccharide gum is in 0.05 - 0.1% by weight and preferably the cross linker is in 0.01 to 0.5% by weight.
The hydrophilic monomer may be selected from a group comprising acrylic acid, methacrylic acid, 2-ethyl hexyl acrylic acid, hydroxy ethyl acrylic acid or hydroxy ethyl methacrylic acid, acrylamide, methacrylamide, vinyl pyrrolidone, acrylonitrile or methacrylonitrile. Preferably acrylic acid may be used.
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The polysaccharide gum used for grafting may be mucilaginous and selected from preferably acacia, xanthan or tragacanth gum.
The crosslinker may be divinyl benzene, ethylene glycol dimethacrylate, methylene bis acrylamide, methylene bis methacrylamide, allyl glycidyl ether or such other compounds known in the art. Preferably ethylene glycol dimethacrylate, divinyl benzene or alkyl glycidyl ether may be used.
Preferably 20 - 30% partial neutralisation of the hydrophilic monomer may be carried out prior to polymerisation.
The alkali used for neutralisation may be selected from sodium hydroxide, carbonate or bicarbonate, potassium hydroxide, carbonate or bicarbonate, or calcium, magnesium or aluminum hydroxide. Preferably potassium hydroxide or carbonate or calcium hydroxide may be used.
The initiator may be ammonium peroxide, benzoyl peroxide, azobis isobutyronitrile, lauroyl peroxide or such other compounds known in the art, preferably benzoyl peroxide and may be used in 0.5 -1.5% by weight of the hydrophilic monomer.
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The polymerisation is preferably carried out at 60 - 80°C.
The organic solvent may be ethyl acetate, isopropyl acetate, butyl acetate, acetone or methyl isobutyl ketone or a mixture thereof, preferably 1:1 :: ethyl acetate : acetone.
The inert atmosphere may be nitrogen or argon, preferably nitrogen.
The synthetic bulk laxative may be dried at preferably 50 - 70°C.
The dried synthetic bulk laxative obtained may be pulverised in known manner to uniform powder of 40/120 mesh size.
The pulverised synthetic bulk laxative of the invention may be formulated into tablets, capsules sachet, biscuits, wafers or other oral dosage forms, using pharmaceutically acceptable excipents such as saccharin, microcrystalline cellulose, magnesium stearate, aspartame, flavours or other such compounds known in the art in known manner.
The synthetic graft polymer bulk laxative comprising a
hydrophilic monomer chemically bonded to a polysaccharide gum
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and crosslinker in the weight percentages as defined in the invention
exhibits high swelling (~ 100 times) in physiological ie intestinal
fluid. The polymer of the invention has mucilaginous slimy texture
and assists bowel movement and cures constipation. The
polysaccharide gum does not undergo digestion in the
physiological fluid and is non-absorbable. Therefore there is no deterioration in swellability of the graft polymer of the invention in physiological fluids on oral ingestion. Due to their high swellability, the polymers of the invention can be conveniently administered in small dQses of 1 - 2 gm / day to be effective. The polymers show relatively less swelling in acidic gastric fluid (6-12 times) than in the intestinal fluid and therefore do not cause pain and abdominal discomfort. The graft polymer laxative of the invention is highly dispersible in the intestinal fluids. Therefore the polymer does not form lumps or agglomerates and swells uniformly invivo. The polymer of the invention is synthetically prepared and hence is not associated with allerginic protein. Therefore, mucous membrane sensitization, irritation or allergic reactions are not caused with the use of this polymer. Since the polymer is not a natural product but is synthetically made, it is resistant to microbial attack and is not prone to contamination during storage.
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Due to the water-swellable property, the polymer of the invention besides as a laxative, may be used in the treatment of diarrhoea and to regulate consistency of effluent in colostomy patients or as a constituent element of sanitary napkins, tampons, paper diapers, wound protecting / healing materials, biological carrier or moisture conserving materials in agriculture.
The following experimental examples are illustrative of the invention but not limitative of the scope thereof.
EXAMPLE - 1
Acrylic acid (25.Og) was neutralised with potassium carbonate (4.5 g). To this tragacanth gum (0.125 gm) was added. Divinyl benzene (0.6 gm) in ethyl acetate and acetone mixture (1:1, 100.0 ml) and benzoyl peroxide (300.0 mg) were added to the above mixture and the mixture was polymerised by refluxing under nitrogen atmosphere for 6 hours at 60°C. The reaction mass was filtered and dried at 50°C for 8 hours to obtain 24.5 gm of the crosslinked acrylic acid-tragacanth gum graft polymer.
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EXAMPLE 2
The procedure of Example 1 was followed using 0.75 gm instead of 0.6 gm of divinyl benzene to obtain 24.1 gm of crosslinked acrylic acid-tragacanth gum graft polymer.
EXAMPLE 3
The procedure of Example 1 was followed using 0.85 gm instead of 0.6 gm of divinyl benzene to obtain 24.8 gm of crosslinked acrylic acid-tragacanth gum graft polymer.
Example 4
The procedure of Example 3 was followed using 0.125 gm instead of 0.85 gm of divinyl benzene and without tragacanth gum to obtain 23.9 gmof crosslinked acrylic acid polymer.
Example 5
The procedure of Example 4 was followed using 0.25 gm instead of 0.125 gm of divinyl benzene to obtain 25.1 gm of the crosslinked acrylic acid polymer.
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Example 6
The procedure of Example 4 was followed using 0.5 gm instead of 0.125 gm of divinyl benzene to obtain 23.9 gmofthe crosslinked acrylic acid polymer.
Example 7
The procedure of Example 1 was followed using 0.125 gm instead of 0.6 gm of divinyl benzene and 1.0 gm instead of 0.125 gm of tragacanth gum to obtain 24.5 gm of the crosslinked acrylic acid-tragacanth gum graft polymer.
Example 8
The procedure of Example 7 was followed using 1.2 gm instead of 1.0 gm of tragacanth gum to obtain 24.8 gm of the crosslinked acrylic acid-tragacanth gum graft polymer.
Example 9
The procedure of Example 7 was followed using 1.5 gm instead of 1.0 gm of tragacanth gum to obtain 24.3 gm of the crosslinked acrylic acid-tragacanth gum graft polymer.
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Example 10
The procedure of Example 7 was followed using 0.08 gm instead of 0.125 gm ofdivinyl benzene and 0.03 gm instead of 1.0 gm of tragacanth gum to obtain 25.6 gmof crosslinked acrylic acid-tragacanth graft polymer.
Example 11
The procedure of Example 7 was followed using 0.1 gm instead of 0.125 gm of divinyl benzene and using 0.125 gm instead of 1.0 gm of tragacanth gum to obtain 23.5 gm of crosslinked acrylic acid-tragacanth gum graft polymer.
Example 12
The procedure of Example 7 was followed using 0.375 gm instead of 1.0 gm of tragacanth gum to obtain 24.1 gmof crosslinked acrylic acid-tragacanth gum graft polymer.
The polymers of Examples 1 to 12 were pulverised and passed through sieve of mesh size 52 and polymer powders of mesh size 85 were retained.
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Example 13
A sachet weighing 1.5 gm was prepared by mixing the following
ingredients:
Graft polymer of Example 12 1.0 g
Citric acid 0.2 g
Aspartame 0.1 g
Lemon juice flavour 0.2 g
Example 14
Tablets were obtained by mixing the following ingredients before
compressing
Graft polymer of Example 12 500.0 mg
Hydroxypropyl cellulose (L-HPC) 30.0 mg
Colloidal silica 2.0 mg
Apricot flavour 1. 0 mg
Vanilla flavour 1. 0 mg
Saccharin 0.1 mg
Magnesium stearate 0.1 mg
Example 15
Hard gelatin capsules were prepared by mixing the following ingredients
and filling into capsules :
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Graft polymer of Example 12 500.0 mg
Magnesium stearate 5.0 mg
Microcrystalline cellulose 50.0 mg
SWELLABILITY TESTS
Swellability tests were carried out on the polymers of Examples 1 to 12 in simulated gastric juice (pH 1.5) and simulated intestinal fluid (pH 7.5) as per USP method ( USP 23 page no 2053). Polymers of Examples 7 to 12 were tested for swellability in bicarbonate solution (pH 8.5) as per the method used for testing the swellability of calcium polycarbophil (Product literature of B F Goodrich and Company) and the results were as follows in Table 1:
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Table 1

Swell weight in gm/gm of polymer
Polymer Pepsin solution (pHl.5) Pancreatin solution (PH 7.5) Bicarbonate solution (pH 8.5)
Example 1 2.4 50.8 -
Example 2 2.1 33.4 -
Example 3 2.0 20.5 -
Example 4 8.3 76.1 -
Example 5 10.1 72.5 -
Example 6 11.5 62.6 -
Example 7 2.8 60.0 111.0
Example 8 3.6 55.5 102.6
Example 9 3.9 45.0 83.2
Example 10 7.5 89.5 165.5
Example 11 8.6 93.8 173.53
Example 12 9.1 95.0 175.53
Calcium polycarbophil 4.60 45.00 38.00
Isphagula husk 30.00 37.85 17.10
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The results of polymers of Examples 4 to 6 when compared to those of Examples 10 to 12 show that the polymers of the invention with the polysaccharide gum incorporated thereinto show high swelling when compared to the polymers without the polysaccharide gum. The results of polymers of Examples 1 to 3 and Examples 7 to 9 show that higher weight percentages of the crosslinker and the polysaccharide gum in the polymer than those defined in the invention, reduce the swelling capacity thereof. Swelling of the polymers of Examples 10 to 12 in pancreatin being ~ 10 times more than in pepsin, the polymers of the invention will exhibit less swelling in the stomach than in the intestine. An observation of the swollen polymers of Examples 10 to 12 showed uniformity in the swelling. This shows that the polymers of the invention do not form lumps or agglomerates. The polymers of the invention show better swellability when compared to isphagula and calcium polycarbophil.
Shrniness test:
A blind study was conducted to determine the sliminess by sense of touch of the polymers of Examples 1 to 12, polycarbophil and isphagula by handing over the pancreatin solution swollen polymers of Examples 1 to 12, calcium polycarbophil and isphagula to 10 adult volunteers. The evalulation was conducted on
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the basis of 4 ratings viz 0 for non-slimy, 1 for slightly slimy, 2 for moderately slimy and 3 for highly slimy feel. The analysis rated the polymers of Examples 10 to 12 and isphagula at 3. The polymers of Examples 1 to 3 were rated 2. The polymers of Examples 4 to 6 and calcium polycarbophil were rated 1.
The results show that the polymers of the invention are very slimy when compared to the other polymers and calcium polycarbophil.
In vivo studies:
In vivo studies were conducted using the polymers of the invention, the details of which are as follows:
Wistar albino rats weighing between 180 - 200 g of either sex were divided into 3 groups consisting of 8 animals each and were housed individually as 3 animals per cage. The distribution of animals in groups, the sequence of trials and the treatment allotted to each group were randomized. The treatment was that the 1st group i.e. control group received phosphate buffer saline [1 ml /kg per oral (p.o)], the 2nd group received polymer of Example 12 (70 mg/kg; p.o.) and the 3rd group received isphagula husk (70
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mg/kg; p.o) and was continued for 7 consecutive days. 30 minutes after administration of either the drug or saline, all the animals were hydrated by administering 5 ml of water by oral route and fed with standard rat chow diet (20 g/rat).
I) Gastro-intestinal motility test:
Following treatment, the rats were fasted for 18 h. To each animal was administered orally, 1 ml of charcoal meal (3% deactivated charcoal in 10% aqueous tragacanth). 1 hour later, each animal was killed and the distance moved by the charcoal meal in the intestine from the pylorus was cut and measured and expressed as a percentage of the distance from the pylorus to the caecum and the results are as in Table 2.
TABLE - 2

Treatment (mg/kg x days) Total length (cm) Movement of charcoal meal (cm) Movement of charcoal meal (%)
Control 83.52 + 9.67 47.58 + 4.66 52.81 ±2.21
Example 12 (70 x 7) 84.50 + 4.53 66.50 + 5.32 82.63+4.84
Isphagula husk (70 x 7) 82.25 ± 6.62 61.32 + 5.98 73.39 ±5.93
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Polymer of Example 12 showed improved bowel movement and its results were found to be statistically significant (P < 0.01). This also proves the high slimy nature of the polymer of the invention.
II) Castor-oil induced diarrhoea in rats
The method followed here was the method of Awouters et al (1978) with modification. The rats were fasted for 18 hours before being treated. One hour later each animal received 1 ml of castor oil orally by gavage and then observed for defacation upto 4 hours and the presence of characteristic diarrhoeal droppings were noted in the transparent plastic dishes placed beneath the individual rate cages. The results were as shown in Table 3:
TABLE - 3

Oral pretreatment at 1 hr. (mg/kg x days) Mean defecations/group Mean no of wet faeces/group
Control 4.32 ±0.82 4.32 + 0.82
Example 12 (70 x 7 ) 2.03 + 0.63 1.16 + 0.21
Isphagula husk (70 x 7 ) 2.36 + 0.34 1.85 + 0.32
Polymer of Example 12 showed good control on diarrhoea with reduced wetness in faecal matter as shown in
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Table 3 and these results were found to be statistically significant (P <0.01).
B. RADIOLOGICAL TESTING FOR LAXATIVE ACTION
Materials & Methods
Wistar albino rats of either sex weighing between 160 - 220 g were used in this study. The animals were divided into four groups. Animals from all groups were housed individually in standard cages with filter paper at the bottom on which a mesh of the same size was placed. The animal was placed on the mesh to avoid coprophasy and for proper collection of faecal matter. The laxative activity was studied over a period of 11 days. From day 1 to 5, i.e predossing period, each animal is provided with 20 g of food and water (ad libitum per day). From day 5 to 10 the animals received their respective treatment at the same time everyday orally as follows:
Rats of group I served as control i.e. they were fed with 2 ml water, group II was treated with isphagula husk (70 mg/kg body weight / day in 2 ml water), group III with calcium polycarbophil (80 mg/kg body weight / day in 2 ml water) and group IV with polymer of Example 10(25 mg /kg body weight /day in 2 ml water).
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After 4 days treatment all the animals were fasted overnight and on the next day the animals were subjected to X-rays after 0.5, 2 and 24 hours to study the intestinal transit (motility), after feeding the animals with barium meal (2 ml/rat). The appearance of barium, a radio opaque substance in different parts of the gastro intestinal tract was observed and the results were as shown in Table 4.
TABLE - 4

Appearance of barium after
Goup 0.5 hr 2hrs 24hrs
I Mid ileum Mid ileum Traces
II Proximal colon Traces

III Distal ileum Descending colon Traces
IV Descending colon Rectum Traces
Polymer of the invention showed better laxative property compared to isphagula husk and calcium polycarbophil, since without 30 mins the polymer of the invention showed a bowel movement upto descending colon whereas use of isphagula husk and calcium polycarbophil showed bowel movements upto proximal colon and
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distal ileum respectively. In addition, use of polymer of the invention showed well maintained barium column, whereas in case of isphagula husk and calcium polycarbophil, the column was broken, which presumably indicates erratic contractions of the intestine and thus abdominal discomfort. Thus the polymer of the invention is a more effective laxative, at a lower dose of 25 mg/kg body weight / day dose when compared to isphagula and calcium polycarbophil at higher doses of 70 mg / kg weight / day and 80 mg/kg weight / day respectively.
At the end of X-ray studies, the water content in the faecel matter from all the groups was determined and the results were as follows in
Table 5.
TABLE - 5

Group Water content (%) Average length of faecal dropping ( mm) Average width of faecal dropping (mm) Bulk volume ml/gm.
I 49 15 5 1.2
II 61.5 16 6 1.2
III 63.4 16 6 1.2
IV 71.2 17 7 2.4
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The faeces of Group IV appeared significantly bulkier than those of Groups I, II and III.
Conclusion
The above observations suggest that polymer of the invention improved the consistency of the faeces (softens the faeces) and increased the gastro-intestinal motility comparable to that of isaphgula and are capable of being used as bulk laxatives and that too at one-third dose. The polymers of the invention solidified the faeces and reduced its water content and can also be used in the treatment of diarrhoea.
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WE CLAIM:
1. A process for the preparation of a synthetic bulk laxative
comprising :
a) 20%- 75% partial neutralization of a hydrophilic
monomer with an alkali;
b) polymerization of the partially neutralised
hydrophilic monomer with 0.01 - 2% by weight of a cross linker
and 0.05% - 3% by weight of a polysaccharide gum in the presence
of an initiator in an organic solvent under inert atmosphere at 30 -
80 ° C, the weight percentages being with respect to the hydrophilic
monomer;
c) drying the synthetic bulk laxative at 30-120°C; and
d) pulverizing the dried synthetic bulk laxative.

2. A process as claimed in claim 1, wherein the hydrophilic monomer is acrylic acid.
3. A process as claimed in claim 1 or 2, wherein 20-30%, partial neutralization of the hydrophilic monomer is carried out.
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4. A process as claimed in any one of claims 1 to 3, wherein the alkali is potassium bicarbonate.
5. A process as claimed in any one of claims 1 to 4, wherein the cross linker is in 0.01 to 0.5% by weight.
6. A process as claimed in any one of claims 1 to 5, wherein the crosslinker is ethylene glycol dimethacrylate, divinyl benzene or allyl glycidyl ether.
7. A process as claimed in any one of claims 1 to 6, wherein the polysaccharide gum is in 0.05 - 0.1% by weight.
8. A process as claimed in any one of claims 1 to 7, wherein the polysaccharide gum is acacia, tragacanth or xanthan gum.
9. A process as claimed in any one of claims 1 to 8, wherein the initiator is benzoyl peroxide.
10. A process as claimed in any one of claims 1 to 9, wherein the organic solvent is 1:1 :: ethyl acetate : acetone mixture.
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11. A process as claimed in any one of claims 1 to 10, wherein the polymerization is carried out at 60 ° C.
12. A process as claimed in anyone of claims 1 to 11, wherein the inert atmosphere is nitrogen.
13. A process as claimed in any one of claims 1 to 12, wherein the synthetic bulk laxative is dried at 50 ° C.
14. A method of making a formulation of a synthetic bulk laxative as claimed in claim 1 comprising mixing a crosslinked graft polymer formed of a hydrophilic monomer partially neutralised from 20% -75%, a polysaccharide gum from 0.05% - 3% by weight and a crosslinker from 0.01% - 2% by weight, the weight percentages being with respect to the hydrophilic monomer with pharmaceutically acceptable excipients.
15. A method of making a formulation as claimed in claim 14, wherein the hydrophilic monomer is 20 - 30% partially neutralised.
16. A method of making a formulation as claimed in claim 14 or 15, wherein the hydrophilic monomer is acrylic acid.
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17. A method of making a formulation as claimed in anyone of claims 14 to 16, wherein the polysaccharide gum is in 0.05 -0.1% by weight.
18. A method of making a formulation as claimed in any one of claims 14 to 17, wherein the polysaccharide gum is acacia, tragacanthor xanthan gum.
19. A method of making a formulation as claimed in anyone of claims 14 to 18, wherein the cross linker is in 0.01 to 0.5% by weight.
20. A method of making aformulation as claimed in any one of
claims 14 to 19, wherein the crosslinker is ethylene glycol
dimethacrylate, divinyl benzene or allyl glycidyl ether.