AU2000268638A1 - A synthetic bulk laxative - Google Patents
A synthetic bulk laxativeInfo
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- AU2000268638A1 AU2000268638A1 AU2000268638A AU2000268638A AU2000268638A1 AU 2000268638 A1 AU2000268638 A1 AU 2000268638A1 AU 2000268638 A AU2000268638 A AU 2000268638A AU 2000268638 A AU2000268638 A AU 2000268638A AU 2000268638 A1 AU2000268638 A1 AU 2000268638A1
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Description
TITLE OF INVENTION A synthetic bulk laxative.
This invention also relates to a process for the preparation of the synthetic bulk laxative and a formulation com risi the same.
Background Art
Laxatives are classified depending on their mechanisms of action. For example, laxatives comprising preparations of sodium phosphate or magnesium sulfate are of the osmotic type. Laxatives 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 their non-acceptable organoleptic properties and poor efficacy.
Yet another type of laxative is bulk laxative which on oral adrninistration sweEs significantty occupying most of the intestinal lumen, thereby improving gastrointestinal motϋity to cure constipation. Bulk laxative is also used in the treatment of diarrhoea. Bulk laxative may comprise semisyiithetic polymers such as calcium polycarbophil or metliyl 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 crosslinker under physiological conditions, it is required to be prescribed in high doses of 4 - 6 g/day ( ie 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, ϊt exhibits low swelling (~ 40 times) in simulated 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 sensitisation of the mucous membrane, irritation and other allergic reactions in the body. Isphagula husk has low dispersibihty in water because of which it forms lumps or agglomerates in aqueous fluids. The lumps swell non-uniformly and adversly 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 acryhc acid or methaerylic acid and a polysaccharide such as starch or derivative 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 gelatinised starch as polysaccharide. Graft polymers of acryhc 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, polymethacryhc 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 gela inisation of starch, the polymers will show low swellabihty (30 to 40 times) in physiological fluids though their swellabihty in water is high. The starch in such graft polymers is likely to undergo digestion n the physiological fluid, and reduce the swellabihty of the graft polymers. Moreover such polymers are not slimy. High percentages of polysaccharides in polymer have been found to reduce the swellabihty thereof in physiological fluids.
Crosslinked, water soluble, water absorbable or water swellable polymers formed of monomers such as acrylates, acryhc acids, acrylamides, acrylonitriles or vinyl pyirohdones and cross linkers are known and reported to be used as absorbing or dehydrating or tliickening 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 Nol05634Bl and JP Patent No
6322178A).
Gums such as iragacanth, acacia or xanthan gum are water swellable and are known to be used as emu fiers, binders, stabilisers, tliickening or suspending agents in food and pharmaceutical industry.
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 adiiiirάstered 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 sensitisation, 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 ύie invention is to provide a synthetic bulk laxative, which is non-absorbable m the intestinal fluid.
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, wliich 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 that does not cause mucous membrane sensitisation, 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 syntlietic bulk laxative, which results in an inert product non-susceptible to microbial contamination during storage.
Another object of the invention is to provide a formulation of a synthetic bulk laxative, wliich has high swelling in physiological fluid and is slimy and assists bowel movement.
Another object of the invention is to provide a formulation of a synthetic bulk laxative, which has less swelling m. stomach than in the intestine and eliminates abdominal pain and discomfort.
Another object of the invention is to provide a formulation of a synthetic bulk laxative, wliich may be administered m low doses of ϊ - 2 gm/day.
Another object of the invention is to provide a formulation of a a synthetic bulk laxative, wliich does not cause mucous sensitisation, irritation or other allergic reactions.
Another object of the invention is to provide a formulation of a synthetic bulk laxative, wliich does not foπn lumps or agglomerates and swells uriiformly.
Another object of the invention is to provide a formulation of a synthetic bulk laxative, which is non-absorbable in the intestinal fluid.
Another object of the invention is to provide a formulation of a synthetic bulk laxative, wliich is inert and non-susceptible to microbial contamination during storage.
According to the invention there is provided a synthetic bulk laxative comprising a crosslinked graft polymer formed of a hydropliihc monomer partially neutralised upto 75%, a polysaccharide gum upto 3% by weight and a crosslinker upto 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) upto 75 % partial neutralisation of a hydrophilic monomer with an alkali;
b) polymerisation of the partially neutralised hydrophilic monomer with a crosslinker upto 2 % by weight and a polysaccharide gum upto 3% by weight, 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) pulverising the dried synthetic bulk laxative.
According to the invention there is also provided a formulation of a synthetic bulk laxative comprising a crosslinked graft polymer formed of a hydrophihc monomer partially neutralised upto 75%, a polysaccharide gum upto 3% by weight and a crosshnker upto 2% by weight, the weight percentages being with respect to the hydrophihc 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 hydrophihc monomer may be selected from a group comprising acryhc acid, mεthacryhc acid, 2-ethyl hexyl acryhc acid, hydroxy ethyl acryhc acid or hydroxy ethyl methacryhc acid, acrylamide, methacrylamide, vinyl pyrrolidone, acrylonitile or methacrylonitrile. Preferably acryhc acid may be used.
The polysaccharide gum used for grafting may be mucilaginous and selected from preferably acacia, xanthan or tragacanth gum.
The crosshnker may be divinyl benzene, ethylene glycol dimethacrylate, methylene bis acrylamide, methylene bis methacrylamide, ally! glycidyl ether or such other compounds known in the art. Preferably ethylene glycol dimethacrylate, divinyl benzene or ally! glycidyl ether may be used.
Preferably 20 - 30% partial neutralisation of the hydrophilic monomer may be carried out prior to polymerisation.
The a kah used for neutralisation may be selected from sodium hydroxide, carbonate or bicarbonate; potassium hydroxide, carbonate or bicarbonate; or calcium, magnesium or aluminium 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 wτeight of the hydrophihc monomer.
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 - 7G°C.
The dried synthetic bulk laxative obtained may be pulverized 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, sachets, biscuits, wafers or other oral dosage
forms, using pharmaceutically acceptable excipients 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 liydropliihc monomer chemically bonded to a polysaccharide gum 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 mucilagonous 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 m swellabihty of the graft polymer of the invention in physiological fluids on oral ingestion. Due to their high swellabihty, the polymers of the mventioii can be conveniently administered in small doses of 1 - 2 gm/day to be effective. The polymers show relatively less sweϋmg in. acidic gastric fluid ( 6 - 12 times) than in tlie intestinal fluid and therefore do not cause pain and abdominal discomfort. The graft polymer laxative of the invention is highly dispersible m 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 aHergjnic protein. Therefore mucous membrane sensitisation, 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.
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 ύie scope thereof.
Example 1 Acryhc acid (25.0 gm) was neutralised with potassium carbonate
(4.5 g). To this tragacanth gum (0.125 g ) was added. Divinyl benzene (0.6 gm) m ethyl acetate and acetone mixture ( 1:1, 100.0 ml) and benzoyl peroxide (300.0 g) were added to the above mixture and the mixture was polymerised by refluxmg 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 crosshnked acryhc acid-tragacanth gum graft polymer.
Example 2 The procedure of Example 1 was followed using 0.75 g instead of 0.6 gm of divinyl benzene to obtain 24.1 g of crosslinked acryhc 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 acryhc 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 g of the 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 acryhc acid polymer.
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 gm of the crosshnked acryhc 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-txagacanth 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 acryhc 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 crosshnked acryhc acid- tragacanth gum graft polymer.
Example 10 The procedure of Example 7 was followed using 0.08 gm instead of 0.125 gm of divinyl benzene and 0.03 gm instead of 1.0 gm of tragacanth gum to obtain 25.6 gm of crosslinked acryhc acid-tragacanth graft polymer.
Example 1 The procedure of Example 7 was followed us g 0.1 gm histead of 0.125 gm of divinyl benzene and using 0.125 gm histead of 1.0 gm of tragacanth gum to obtain 23.5 gm of crosshnked acryhc 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 gm of crosslinked acryhc acid-tragacanth gum graft polymer.
The poiymers of Examples 1 to 12 were pulverised and passed through sieve of mesh size 52 and polymer powders of mesh size 85 were retained.
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 obtahied by rnixhig 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 nig
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:
Graft polymer of Example 12 500.0 mg Magnesium stearate 5.0 mg
Macrocrystalline cellulose 50.0 mg
SweBa ϋty Tests:
Swellabihty 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 the USP method ( SP 23 page no 2053) . Polymers of Examples 7 to 12 were tested for swellabihty in bicarbonate solution (pH 8.5) as per the method used for testing the swehabihty of calcium polycarbophil (Product, hterature of B F Goodrich and Company) and the results were as follows hi Table 1:
Table 1
Swell weight in gm gm of polymer
Polymer Pepsin Pancreaim Bicarbonate solution solution solution
<PH 1.5) (pH 7.5) (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
Calciiϊm polycarbophil 4.60 45.00 38.00
Isphagαiahask 30.00 37.85 17.10
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 polysachharide 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 swelhng capacity thereof. Swelling of the polymers of Examples 10 to 12 in pancreatin being -10 times more than that 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 unifoπnity in the swelling. This shows that the polymers of the invention do not form lumps or agglomerates. The polymers of the invention show better swellabihty when compared to isphagula and calcium polycarbophil.
Sfiitimess test:
A blind study was conducted to detem ine the shminess 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, calciumpolycarbophil and isphagula to 10 adult volunteers. The evaluation was conducted on 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 potycarbophil. in vivo studies .
In vivo studies were conducted using the polymers of the invention, the details of wliich are as follows :
Wistar albino rats weighing between 180 - 200 g of either sex were divided into 3 groups consistmg of 8 aiiimals each and were housed individually as 3 animals per cage. The distribution of animals in groups, the sequence of trials and the treatment alloted to each group were randomized. The treatment was thai 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 g kg; p.o.) and was continued for 7 consecutive days. 30 minutes after aάministration of either the drug or saline, al the animals were hydrated by administering 5 ml of water by oral route and fed with standard rat chow diet (20 g/rat).
ϊ) Gastro-mtestiiial motility test: Following treatment, the rats were fasted for 18 h. To each animal was adimmstered 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 Total length Movement of Movement
(mg kg x days) (cm) charcoal meal of charcoal (cm) meal
Control 83.5219.67 47.58±4.66 52.8112.21
Example 12 (70x7) 84.50+4.53 66.50±5.32 82.6314.84 Isphagula husk (70x7) 82.25+6.62 61.32+5.98 73.39+5.93
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 shiny 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 diarrhoea! 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 lh Mean defacations group Mean no of (mg/kg days) wet faeces/ group
Control 4.3210.82 4.3210.82
Example 12 (70 x 1) 2.03+0.63 1.16+0.21
Isphagula husk (70 x 7) 2.36+0.34 1.8510.32
Polymer of Example 12 showed good control on diarrhoea with reduced wetness in faecal matter as shown in Table 3 and these results were found to be statistically significant (P < 0.01).
Ill) Radiological testing for laxative action:
Materials and 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 inchviduvally 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, ie predossing period, each animal is provided with 20 g of food and water (ad hbitum per day). From day 5 to 10 the animals received their respective treatment a the same 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 rng&g 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).
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 (motihty), 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
Appe: arance of barium after
Group 0.5 hr 2hrs 24 hrs
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 within 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 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 ie faecel matter from all the groups was determined and the results were as follows in Table 5. Table 5
Group Water content Average length Average width Bulk of faecal dropping of faecal dropping volume
(%) (mm) (mm) (ml/pa)
ϊ 49 15 5 1.2
E 61.5 16 1.2
HI 63.4 16 6 1.2
IV 71.2 17 7 2.4
The faeces of Grou IV appeared significantly bulkier than those of Groups I, II and III.
Conclusion:
5 The above observations suggest that polymer of the invention improved the consistency of the faeces (softens the faeces) and increased the gastro-hitestinal motihty 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 i o be used in the treatment of diarrhoea.
Claims
1) A synthetic bulk laxative comprising a crosshnked graft polymer formed of a hydrophihc monomer partially neutralised upto 75%, a
5 polysaccharide gum upto 3% by weight and a crosshnker upto 2% by weight; the weight percentages being with respect, to the hydrophihc monomer.
2) A bulk laxative as claimed in cl m 1, wherein the hydrophihc monomer is 20-30% partially neutralised. 0
3) A bulk laxative as claimed in claim 1 or 2, wherein the hydrophihc monomer is acryhc acid.
4) A bulk laxative as claimed in any one of claims 1 to 3, wherein s the polysaccharide gum is hi 0.05 - 0.1% by weight.
5) A bulk laxative as claimed in any one of claims 1 to 4, wherein the polysaccharide gum is acacia, tragacanth or xanthan gum.
0 6) A bulk laxative as claimed in any one of claims 1 to 5, wherein the cross linker is hi 0.01 to 0.5% by weight.
7) A bulk laxative as claimed in any one of claims 1 to 6, wherein the crosslinker is ethylene glycol dimethacrylate, divinyl benzene or allyl 5 glycidyl ether.
8) A process for the preparation of a synthetic bulk laxative comprising:
a) upt 75 % partial neutrahsation of a hydrophihc monomer with an alkali;
b) polymerisation of the partially neutralised hydrophihc monomer with upto 2 % by weight of a cross linker and upto 3% by weight of a polysaccharide gum in the presence of an initiator n an organic solvent under inert atmosphere at 30 - 80°C, the weight percentages being with respect to the hydrophihc monomer;
c) drying the synthetic bulk laxative at 30 - 120° C; and
d) pulverising the dried synthetic bulk laxative.
9) A process as claimed in claim 8, wherein the hydrophihc monomer is acryhc acid.
10) A process as claimed in claim 8 or 9, wherein 20 - 30% partial neutralisation of the hydrophihc monomer is carried out.
11) A process as claimed in any one of claims 8 to 10, wherein the alkali is potassium bicarbonate. 12) A process as claimed in any one of claims 8 to 11, wherein the cross linker is hi 0.01 to 0.5% by weight.
13) A process as clahned in any one of claims 8 to 12, wherein the crosslinker is ethylene glycol dimethacrylate, divinyl benzene or allyl giycidyl ether.
14) A process as claimed in any one of claims 8 to 13, wherein the polysaccharide gum is in 0.05 - 0.1% by weight.
15) A process as claimed in any one of claims 8 to 14, wherein the polysaccharide gum is acacia, tragacanth or xanthan gum.
16) A process as claimed in any one of claims 8 to 15, wherem the initiator is benzoyl peroxide.
17) A process as claimed in any one of claims 8 to 16, wherein the organic solvent is 1:1 ;: ethyl acetate ; acetone mixture.
18) A process as claimed in any one of claims 8 to 17, wherem the polymerisation is carried out at 60 °C.
19) A process as claimed in any one of claims 8 to 18, wherein the inert atmosphere is nitrogen. 20) A process as claimed in any one of claims 8 to 19, wherein the synthetic bulk laxative is dried at 50°C.
21) A process for the preparation of a synthetic bulk laxative s substantially as herein described particularly with reference to Examples 10 to
12.
22) A formulation of a synthetic bulk laxative comprising a crosshnked graft polymer formed of a hydrophihc monomer partially 0 neutrahsed upto 75%, a polysaccharide gum upto 3% by weight and a crosshnker upto 2% by weight, the weight percentages being with respect to the liydropliihc monomer, mixed with pharmaceutically acceptable excipients.
23) A. formulation as claimed in claim 22, wherein the hydrophilic s monomer is 20 - 30% partially neutrahsed.
24) A formulation as claimed in claim 22 or 23, wherein the hydrophihc monomer is acryhc acid.
0 25) A formulation as claimed in anyone of claims 22 to 24, wherein the polysaccharide gum is in 0.05 - 0.1% by weight.
26) A formulation as claimed in any one of claims 22 to 25, wherein the polysaccharide gum is acacia, tragacanth or xanthan gum. 5
27) A formulation as claimed hi any one of claims 22 to 26, wherein the cross linker is in 0.01 to 0.5% by weight. 28) A formulation as claimed in any one of claims 22 to 27, wherein the crosslinker is ethylene glycol dhnethacrylate, divinyl benzene or ahyl glycidyl ether.
29) A formulation as claimed in any one of claims 22 to 28, which is in the form of tablets, capsules, sachets, biscuits or wafers.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/IN2000/000064 WO2002000226A1 (en) | 2000-06-29 | 2000-06-29 | A synthetic bulk laxative |
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| AU2000268638A1 true AU2000268638A1 (en) | 2002-03-28 |
| AU2000268638B2 AU2000268638B2 (en) | 2004-09-23 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU6863800A Pending AU6863800A (en) | 2000-06-29 | 2000-06-29 | A synthetic bulk laxative |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US6969511B1 (en) |
| EP (1) | EP1311275B1 (en) |
| JP (1) | JP3880928B2 (en) |
| AT (1) | ATE275958T1 (en) |
| AU (2) | AU6863800A (en) |
| BR (1) | BR0017284A (en) |
| CA (1) | CA2413143A1 (en) |
| DE (1) | DE60013917T2 (en) |
| ES (1) | ES2228597T3 (en) |
| WO (1) | WO2002000226A1 (en) |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE535125A (en) * | 1954-01-25 | |||
| US4070348A (en) | 1973-07-25 | 1978-01-24 | Rohm Gmbh | Water-swellable, bead copolymer |
| US3997484A (en) | 1974-04-03 | 1976-12-14 | The United States Of America As Represented By The Secretary Of Agriculture | Highly-absorbent starch-containing polymeric compositions |
| JPS51125468A (en) | 1975-03-27 | 1976-11-01 | Sanyo Chem Ind Ltd | Method of preparing resins of high water absorbency |
| US4267103A (en) | 1978-12-07 | 1981-05-12 | The B. F. Goodrich Company | Solvent polymerization of carboxyl containing monomers |
| CA1213397A (en) * | 1980-10-20 | 1986-10-28 | Judith L. Page | Weight control with alkyl styrene polymers |
| US4525527A (en) | 1982-01-25 | 1985-06-25 | American Colloid Company | Production process for highly water absorbable polymer |
| NZ205449A (en) | 1982-09-07 | 1986-10-08 | Unilever Plc | Sulphonated,porous,cross-linked polymeric material |
| US4535098A (en) | 1984-03-12 | 1985-08-13 | The Dow Chemical Company | Material for absorbing aqueous fluids |
| DE3613309A1 (en) | 1986-04-19 | 1987-10-22 | Huels Chemische Werke Ag | METHOD FOR PRODUCING WATER-ABSORBING AND WATER-SWELLABLE POLYSACCHARIDE GRAFT POLYMERS |
| DE3738602A1 (en) | 1987-11-13 | 1989-05-24 | Cassella Ag | HYDROPHILY-SOURCE-PURPLE POLYMERISES, THEIR PREPARATION AND USE |
| GB8813552D0 (en) | 1988-06-08 | 1988-07-13 | Unilever Plc | Thickening system |
| US5221722A (en) | 1988-11-28 | 1993-06-22 | The B. F. Goodrich Company | Crosslinked polyacrylic acid |
| DE3911433A1 (en) | 1989-04-07 | 1990-10-11 | Cassella Ag | HYDROPHILIC SWELLABLE GRAFT POLYMERISATES, THEIR PRODUCTION AND USE |
| US5354290A (en) | 1989-05-31 | 1994-10-11 | Kimberly-Clark Corporation | Porous structure of an absorbent polymer |
| DE4029592C2 (en) | 1990-09-19 | 1994-07-14 | Stockhausen Chem Fab Gmbh | Polymer-based swelling agents and absorbents with improved degradability and absorption of water, aqueous solutions and body fluids, and their use for the production of hygiene articles and for soil improvement |
| TW320647B (en) | 1993-02-24 | 1997-11-21 | ||
| JPH06322178A (en) | 1993-05-14 | 1994-11-22 | Sanyo Chem Ind Ltd | Salt-resistant absorbent composition |
| US5626154A (en) | 1993-09-13 | 1997-05-06 | The Gillette Company | Method and system for shaving including a lubricant and a water-swellable polymer |
| FR2717815A1 (en) | 1994-03-25 | 1995-09-29 | Gel Sciences Inc | New gel-forming hyaluronic acid deriv. polymers or copolymers |
| GB9413605D0 (en) | 1994-07-06 | 1994-08-24 | American Colloid Co | Method of increasing the size and absorption under load of super-absorbent fine particles by impregnation with an aqueous acrylic monomer solution |
| US5804605A (en) | 1994-11-10 | 1998-09-08 | The Procter & Gamble Company | Absorbent material |
| US5985944A (en) | 1994-12-08 | 1999-11-16 | Nippon Shokubai Co., Ltd. | Water-absorbent resin, process for production thereof, and water-absorbent resin composition |
| DE19612628A1 (en) | 1996-03-29 | 1997-10-02 | Hoechst Ag | Process for the production of porous, hydrophilic, highly swellable hydrogels |
-
2000
- 2000-06-29 DE DE60013917T patent/DE60013917T2/en not_active Expired - Fee Related
- 2000-06-29 ES ES00956777T patent/ES2228597T3/en not_active Expired - Lifetime
- 2000-06-29 JP JP2002505008A patent/JP3880928B2/en not_active Expired - Fee Related
- 2000-06-29 EP EP00956777A patent/EP1311275B1/en not_active Expired - Lifetime
- 2000-06-29 AU AU6863800A patent/AU6863800A/en active Pending
- 2000-06-29 AU AU2000268638A patent/AU2000268638B2/en not_active Ceased
- 2000-06-29 BR BR0017284-7A patent/BR0017284A/en not_active Application Discontinuation
- 2000-06-29 WO PCT/IN2000/000064 patent/WO2002000226A1/en not_active Ceased
- 2000-06-29 US US10/130,780 patent/US6969511B1/en not_active Expired - Fee Related
- 2000-06-29 AT AT00956777T patent/ATE275958T1/en not_active IP Right Cessation
- 2000-06-29 CA CA002413143A patent/CA2413143A1/en not_active Abandoned
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