FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
PROVISIONAL SPECIFICATION
(See section 10, rule 13)
"AN IMPROVED PROCESS FOR PREPARATION OF PHOSPHATE BINDING POLYMER"
EMCURE PHARMACEUTICALS LIMITED of Emcure House, T-184, MIDC, Bhosari, Pune - 411 026, Maharashtra, India.
The following specification particularly describes the invention.

AN IMPROVED PROCESS FOR PREPARATION OF PHOSPHATE BINDING POLYMER
INTRODUCTION
Hyperphosphatemia is a disease associated with acute and chronic renal failure and occurs when the serum phosphorus level is greater than 5 mg/dL (1.6 mmol/L), usually in the form of inorganic phosphorus. Hyperphosphatemia involves decreased Ca++ due to increased serum phosphorus, increased parathyroid hormone secretion, and associated sequelae (Ref: http://www.phosphoruscontrol.com/HY/Default.aspx).
Therapeutic efforts directed toward the control of hyperphosphatemia include dialysis, dietary phosphate reduction, and oral administration of insoluble phosphate-binding agents. As dialysis and dietary phosphate reduction alone is not able to sufficiently maintain normal phosphorus level in hyperphosphatemial patients, a combination of therapies must be used such as use of one or more phosphate binders, which is routinely used to treat these patients (Ref: US 5 496 545 A).
Phosphate binding agents act to reduce serum phosphorus ingested through the diet and include calcium, aluminium and magnesium salts or organic polymers such as poly (allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride.
Calcium based phosphate binders have been widely used to bind intestinal phosphate and prevent absorption. Calcium carbonate and calcium acetate are the most commonly used calcium based phosphate binders, although calcium citrate, ketovalin, and alginate are also available. The ingested calcium combines with phosphate to form insoluble calcium phosphate salts. Side effects associated with these agents limit their effectiveness. The major side effect of this therapy is hypercalcemia. Hypercalcemia causes serious side effects such as renal failure, confusion etc. Treatment with calcium base phosphate binders requires frequent monitoring of serum calcium level (Ref: US 5 496 545 A; http://www.phosphoruscontrol.com/PH/CalciumBasedBinders.aspx).
Aluminum is also an effective phosphate binder and is administered in the form of aluminum hydroxide, Al (OH) 3 gel and marketed as "Amphojel®". These compounds form complex
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with intestinal phosphate, to form highly insoluble aluminium phosphate. Prolong use of these gels may lead to aluminum toxicity accompanied by symptoms such as myopathy, severe bone disease and anemia (Ref: US 5 496 545 A and http://www.phosphoruscontrol.com/PH/AluminumBasedBinders.aspx).
Magnesium salts are also known to work as phosphate binder however; they are rarely used because of risk of hypomagnesaemia in renal failure.
Organic polymers are also used as phosphate binders. The said organic polymers are, for example the ion exchange resins like Dowex , XF43311 etc. These resins have several drawbacks like need for high dosage, poor binding capacity etc. (Ref: US 5 496 545 A).
Poly (allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride is one of the therapeutic drug used for the treatment of hyperphosphatemia. It is a copolymer of allylamine and epichlorohydrin, which is a phosphate binder used to reduce the absorption of dietary phosphate. It is used to reduce the serum phosphorus in patients with severe kidney disease known as End Stage Renal Disease (ESRD).
Poly(allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride is marketed by Geltex Pharmaceuticals after USFDA approved the active ingredient in October 1998 for the treatment of high level of serum phosphorus in patients with end-stage renal disease. This active ingredient, which is both calcium-free and aluminum-free, enables the fast treatment of hyperphosphatemia without the risks associated with other treatments. Poly (allylamine-co-N.N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride treatment also results in a lowering of low-density lipoprotein (LDL) and total serum cholesterol levels. (Ref: http://www.centerwatch.com/patient/drugs/dru640.html) and label information of poly (allylamine-co-N, N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride, available on USFDA website).
BACKGROUND OF THE INVENTION:
Poly (allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane)hydrochloride of formula (I) is a poly(allylamine hydrochloride) cross-linked with epichlorohydrin in which 40% amines are protonated.
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Poly(allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane)hydrochloride is a
polymeric phosphate binder, available in the form of tablet and capsules.

Poly (allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride of formula (I) was first disclosed in SU 4 174 41 assigned to Tashkent Polytechnic Institute in 1972. This patent discloses that epichlorohydrin is treated with allylamine at 40-50°C to give a water-soluble flocculant co-polymer.
US 4 605 701 (assigned to Nitto Boseki Co., Ltd.) discloses the preparation of compound of formula (I), according to method summarized in Scheme-1.
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Scheme-1: Method as disclosed in US 4 605 701 for preparation of compound of formula
(I).
The method disclosed in US 4 605 701 for the preparation of compound of formula (1) comprises reaction of allylamine of formula (II) with 35% concentrated hydrochloric acid at a temperature of 5°C to 10°C. Excessive water is distilled off under reduced pressure at 60°C. Allylamine hydrochloride of formula (IIA), thus prepared was dried on anhydrous silica gel and reacted with an aqueous solution of 2, 2'-diamidinyl-2, 2'-azopropane dihydrochloride
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in two lots with stirring for 30 hours after each addition, between 48°C and 52°C. Reaction mixture was quenched with methanol. Poly (allylamine hydrochloride) of formula (III) was isolated by filtration and dried at 50°C under reduced pressure.
An aqueous solution of polyallylamine was prepared by neutralizing compound of formula (III) with an aqueous solution of sodium hydroxide. Epichlorohydrin (IV) was added to an aqueous solution of polyallylamine and stirred for two minutes. The resulting mixture was added into a mixture of chlorobenzene, o-dichlorobenzene and Silvan S-83, to obtain a dispersion, which was allowed to cross-link at 25°C for 30 minutes and at 50°C for 2 hours. The desired compound was filtered and washed successively with methanol, IN sodium hydroxide, and D.M water. The compound of formula (I) was then dried under reduced pressure at 50°C.
The above embodiment for the preparation of compound of formula (I) has the following disadvantages, which are:
a) Use of sodium hydroxide as a base results in the opening of the epoxide ref: US 6982349, column 5 and 6.
b) Use of sodium hydroxide as a base results in the hydrolysis of the epichlorohydrin used i.e. replacement of the chloride ref: US 6982349, column 5 and 6.
c) Necessity to use higher quantities of epichlorohydrin to compensate with the losses of epichlorohydrin, while reacting with NaOH.
d) The use of inorganic base may result in poor phosphate binding property.
e) The process for the preparation of compound (I) utilizes Class 2 solvents such as chlorobenzene, o-dichlorobenzene for the reaction, which in turn makes the process hazardous for human health and environment, and
f) The above process also requires a dispersion stabilizer like Silvan S-83, which makes the process uneconomical.
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US 2004/0028803 Al discloses synthesis of compound of formula (1) in the form of gel, comprising reaction of poly (allylamine hydrochloride) (III) with epichlorohydrin of formula (IV) in an aqueous solution, at a pH between 10.0 and 10.4 adjusted by addition of 50% caustic lye, and maintaining the temperature between 5°C to 10°C followed by a process of gelling for 24 hours.
This method is lengthy and time consuming since the process requires 24 hours for formation of gel. Further the use of caustic lye might result in the opening of the epichlorohydrin or hydrolysis of the epichlorohydrin thus decreasing the yields.
US 5 496 545 (assigned to Geltex Pharmaceuticals) discloses a method for preparation of poly(allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride of formula (I), which is prepared from allylamine of formula (II) via preparation of poly(allylamine hydrochloride) of formula (III), according to the method summarized in Scheme-2


Scheme-2: Method as disclosed in US 5 496 545 for preparation of compound of formula
(I).
The method disclosed in US 5 496 545 for preparation of compound of formula (I) comprises of two steps:
i) reacting allylamine (II) with concentrated hydrochloric acid in aqueous medium to
form allylamine hydrochloride (IIA), followed by removal of water by vacuum distillation at 60°C-70°C,
ii) adding the catalyst azobis(amidinopropane) dihydrochloride in two lots and stirring the reaction for 24 hours and 44 hours respectively, after the addition of each lot, to form poly (allylamine hydrochloride) of formula (III),
iii) separating out compound (III) after quenching with methanol, followed by filtering and leaching with methanol repeatedly, and
iv) reacting epichlorohydrin (IV) with compound (III) in an aqueous medium, by adjusting pH 10 with solid sodium hydroxide and curing for 18 hours, followed by quenching with isopropanol to give compound of formula (I), which was vacuum dried for 18 hours.
The above process also has several drawbacks like:
a) Use of sodium hydroxide as a base results in the opening of the epoxide ref: US 6982349, column 5 and 6.
b) Use of sodium hydroxide as a base results in the hydrolysis of the epichlorohydrin used i.e. replacement of the chloride ref: US 6982349, column 5 and 6.
c) Necessity to use higher quantities of epichlorohydrin to compensate with the losses of epichlorohydrin, while reacting with NaOH.
d) Water has to be removed under vacuum during the preparation of poly (allylamine hydrochloride) of formula (III). Removal of water by distillation consumes lot of energy, which makes the process cumbersome, time consuming and tedious on commercial scale.
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e) Due to hygroscopic nature of the intermediate of formula (III), the filtration has to be carried out under stringent conditions.
f) Further, there is a danger of loss in yield during filtration and leaching, which is done repeatedly. Repeated methanol washing and filtration generates large quantity of effluent, that has to be either recycled by distillation or disposed in the effluent treatment plant.
US 6,290,947 (assigned to Geltex Pharmaceuticals) discloses the preparation of compound of formula (I) comprising reaction of poly (allylamine hydrochloride) of formula (III) in an aqueous medium, at a pH of 10.5 with solid sodium hydroxide, until homogenous mixture was formed. Reaction with epichlorohydrin of formula (IV) was carried out at a pH of 10.2 (Ref: Example 5 of US 6 290 945) and the reaction mixture cured for 18 hours to provide a gel, which is broken up with Kitchen Aid Mixer. Further, washings are given until the conductivity of the effluent was equal to 16.7 mS/cm. The co-polymer of formula (I) was air-dried at 60°C for 5 days.
The above process, although it seems to be commercially viable, has some limitations like:
a) Use of sodium hydroxide as a base results in the opening of the epoxide ref: US 6982349, column 5 and 6.
b) Use of sodium hydroxide as a base results in the hydrolysis of the epichlorohydrin used i.e. replacement of the chloride ref: US 6982349, column 5 and 6.
c) Necessity to use higher quantities of epichlorohydrin to compensate with the losses of epichlorohydrin, while reacting with NaOH.
d) During the process, pH was reduced to a specific range between 10.2 and 10.5. Maintaining pH on a commercial scale, at a precise pH is very tedious. Further, monitoring the sharp pH for a long period is cumbersome.
e) Use of Kitchen Aid Mixer for breaking gel on commercial scale is another limitation.
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f) Monitoring the washing process of final gel till the conductivity of effluent equals 16.7 mS/cm is cumbersome, and puts limitation on online quality control, adds additional manpower, requires more analytical instruments.
g) The final product of formula (I) prepared by this method takes 5 days for drying, thereby increasing the time cycle for each run. This increases drier occupancy and utility for a longer time, thereby, making the process uneconomical.
US 6 525 113 discloses the preparation of Poly(allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride of formula (I) comprising reaction of an aqueous solution of Poly(allylamine hydrochloride) of formula (III) in presence of sodium hydroxide, with epichlorohydrin of formula (IV) at temperature between 20°C to 30°C. The reaction was carried out in a water-miscible solvent like acetonitrile.
It should be noted that this method also utilizes a Class 2 solvent like acetonitrile (methyl cyanide), which has got quite a low exposure limit of 410 ppm. Utilization of such a hazardous cyanide solvent on an industrial scale makes the process environmentally dangerous and less feasible.
Considering all the above shortcomings in the prior art, the applicant has developed a simple and industrially viable process for the preparation of compound of formula (I), which is one-pot reaction, avoiding isolation of compound of formula (III) and avoiding the use of the inorganic base. The method embodied in this invention increases the yields, reduces the time cycle for each batch run, reduces cost, efforts and thereby, makes the process commercially viable.
OBJECT OF THE INVENTION
An object of the invention is to provide simple and cost effective process for the preparation of poly (allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride of formula (I).
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Another object of the invention is to provide a single-pot process for the preparation of poly (allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride wherein the process makes use of the organic bases.
Yet another object of the invention is to provide a single-pot process for the preparation of poly (allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride wherein the overall period for completion of the batch is reduced, making the process suitable for commercial applications.
SUMMARY OF THE INVENTION:
One aspect of the invention is to provide an economical, simple and improved process for the preparation of poly (allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride of formula (I).
Another aspect of the invention relates to an industrially feasible, preparation of poly (allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride of formula (I), which comprises reaction of allylamine of formula (II) with hydrochloric acid in presence of a catalyst i.e. azobis(amidinopropane) dihydrochloride, and optionally a solvent to form a poly (allylamine hydrochloride) of formula (III), which is treated in situ with epichlorohydrin of formula (IV), in the presence of an organic base, at a pH between 8 to 11 in an aqueous medium.
Further aspect of the invention relates to a simple and commercially viable process for the preparation of poly(allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride of formula (I), in a single pot, comprising reaction of allylamine of formula (II) with hydrochloric acid, in presence of catalyst i.e. azobis (amidinopropane) dihydrochloride, to form poly(allylamine hydrochloride) (III), which on further reaction with epichlorohydrin (IV) at a pH between 9 to 11, leads to the formation of poly(allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride of formula (I).
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DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to an improved method for the preparation of poly (allylamine-co-N, N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride of formula (I), using organic base. The said process broadly comprises the steps of:
a) reacting allylamine of Formula (II) with hydrochloric acid in an organic or inorganic to get allylamine hydrochloride of formula IIA

b) reacting allylamine hydrochloride in-situ in presence of catalyst to get polyallylamine hydrochloride of Formula (III), and

c) reacting pollyallylamine hydrochloride of Formula (III) with epichlorohydrine in the presence of organic base to get Sevelamer.
Epichlorohydrine
Poly (allylamine hydrochloride) »- Sevelamer Hydrochloride
(III) organic base (|)
d) optionally isolating Sevelamer by treating with an organic solvent
Preparation of compound (I)
In an embodiment, poly (allylamine-co-N, N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride of formula (I) is prepared according to the Scheme-3 below:
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Method for the preparation of compound of formula (I) according to the present invention.
a) reacting allylamine of formula (II) with concentrated hydrochloric acid to form
allylamine hydrochloride followed by removal of water under vacuum and adding an
aqueous solution of catalyst azobis (amidinopropane) dihydrochloride, and stirring the
reaction mixture at a temperature between 50°C and 55°C after the addition of
catalyst,
b) adding water to the reaction mixture and adjusting the pH of the reaction mixture between 8.0 and 11.0 with an organic base,
c) adding epichlorohydrin of formula (IV) into the reaction mixture at room temperature and keeping for curing for 15 to 20 hours at 40°C.
d) quenching the reaction mass with an organic solvent to separate the compound of formula (I), followed by leaching the filtered solid with an inorganic and organic solvent and filtering the same, and
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e) air-drying at 70°C -75°C for 25 to 35 hours.
In the present invention, all steps are carried out in a single step i.e. the preparation of compound of formula (I) is a one pot reaction, which obviates the need for isolation of compound (III), thereby reducing the time cycle for each batch run and making the process cost-effective.
The compound of formula (I) is a very important and a very costly copolymer used for phosphate binding, in the treatment of hyperphosphatemia. It is very important that compound of formula (I), is obtained in high yield with desired specifications, without utilization of additional steps of purification and isolation of intermediate (III).
The reaction of allylamine and concentrated hydrochloric acid is carried out between the temperatures -10°C to 10°C. The preferred temperature is between -5°C and 5°C to form allylamine hydrochloride. The reaction mass pH is adjusted up to 3.0.
Excess water was distilled off at the temperature between 45°C and 60°C. The preferred temperature is around 50°C which removes the unreacted allyl-amine and other volatile impurities.
A catalyst like azobis(amidonopropane) dihydrochloride is added and stirred for around 90 hours. The reaction is carried out at a temperature selected between 45°C and 70°C. The preferred temperature is between 50°C to 55°C for preparation of poly (allylamine hydrochloride) of formula (III). Any other similar catalyst such as 4-4"-azobis (4-cyanovaleric acid), l,1-azobis(cyclohexene carbonitrile), benzoylperoxide, cumene hydroperoxide may also be employed.
The addition of epichlorohydrin of formula (IV) is carried out by adjusting the pH of reaction mass with an organic base selected from the group comprising of triethylamine, diisopropylethylamine, diazabicycloundecene, tromethamine, hexamine, dimethylamino pyridine.
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For a batch size of 100g of Allyl amine (1.73 mol), the amount of the organic base used lies in the range of 0.71 mol to 1.07 mol.
The amount in moles of triethylamine added is between 0.71 to 1.07 mols.
The amount in moles of diisopropylethylamine added is between 0.97 to 1.5 mols.
The compound of formula (I) is obtained by co-polymerization of compound of formula (III) with epichlorohydrin of formula (IV) after adjusting the pH of the reaction mixture with an organic base. The co-polymerization of compound (III) is carried out at a pH between 9 and 11. The preferred pH range is between 9 and 10.
The addition of epichlorohydrin (IV) to the reaction mixture-containing compound (III) is carried out at a temperature between 25°C and 40°C. The preferred temperature is between 30°C and 35°C.
The cross linked polymer of formula (I) is obtained by stirring for 15 to 20 hours, but preferably 18 hours at a temperature between 30°C and 50°C. The preferred temperature is between 35°C and 45°C.
The compound of formula (I) is obtained by quenching the reaction mixture with a water-miscible protic or aprotic organic solvent. The preferred solvent is a water-miscible protic solvent.
Water miscible protic solvents are selected from the group like alcohols, thiols, etc. The preferred water-miscible protic solvent is an alcohol.
The alcohol employed is selected from the group comprising of methanol, ethanol, isopropanol etc. The preferred alcohol is isopropanol.
The reaction mixture is filtered and the wet cake is then leached separately with an inorganic or a organic solvent. The inorganic solvent utilized for leaching is water. Organic solvents utilized for the leaching is selected from the group comprising of alcohol, nitrile, hydrocarbons etc. The preferred organic solvent is an alcohol.
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The alcohol employed is selected from the group comprising of methanol, ethanol, isopropanol etc. The preferred alcohol is isopropanol.
The compound of formula (I), thus obtained by the process of the present invention exhibits a phosphate-binding activity required for the pharmaceutical preparation.
Thus, the present invention is advantageous in following ways:
1) Use of an organic base for polymerization in place of an inorganic base, which avoids the hydrolysis or the opening of the epoxide of epichlorohydrin.
2) The method is quick, cheap and industrially feasible.
3) The process utilizes comparatively safer solvents having higher exposure limits like alcohols, instead of nitriles such as acetonitrile or chlorinated solvents like chlorobenzene and o-dichlorobenzene. Avoids use of hazardous solvents such as methyl cyanide.
4) The process reduces the load on effluent by preparing compound (I) by eliminating the step of repeated leaching or washing of compound (III), also by using less quantities of epichlorohydrin.
5) Use of organic bases during the preparation of compound (I) from compound (III), makes the process comparatively more feasible than the use of solid sodium hydroxide as addition of solid sodium hydroxide makes the reaction suddenly exothermic and due to slow dissolution of solid sodium hydroxide, one cannot have an idea about the exact pH of the reaction mass, whereas organic bases mix easily due to which the reaction temperature and pH is controlled effectively.
6) Addition of concentrated HC1 to allyl amine minimizes the loss of allyl amine, allyl amine is less exposed to light, air and moisture.
7) Polyallylamine hydrochloride formed is not isolated and carried over as such for copolymerization offering following advantages:

a) material loss is minimum and
b) operation cost is low as equipment occupancy is less.
The principles, preferred embodiments, and modes of operation of the present invention have been described in the foregoing specification. The invention which is intended to be protected herein, however, is not to be construed limited to the particular forms disclosed, since these
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are to be regarded as illustrative rather than restrictive. Variations and changes may be made by those skilled in the art, without departing from the spirit of the invention.
The present invention is more particularly illustrated in the following example(s), but is not to limit the scope of the present invention.
Examples:
Example-1:
132 Kg of Hydrochloric acid was added in the reactor at room temperature under stirring. The reaction mass was cooled to 0 to -5°C. Pre-chilled allyl amine (75 Kg) was added in the reactor at 0 to -5°C. After the completion of the addition the reaction mixture was brought to room temperature. The reaction mixture was distilled out. The slurry of the azobis (amidinopropane dihydrochloride) was added under stirring in two lots. To another reactor was charged methanol. The reaction mixture was added slowly to methanol and stirred for an hour. The reaction mixture was stopped stirring and the reaction was allowed to settle for half an hour at room temperature. The supernatant methanol was decanted. The solid was degassed till the mass became thick. Water was charged to the reaction mixture and stirred to get a clear solution. Water was distilled out and reaction mixture was cooled.
Example-2:
To a reactor was charged water (150 ml) and cooled to 0-5°C. Allylamine (75g) was added to the chilled water. The reaction mixture was cooled to -10 to 0°C. Then fuming hydrochloric acid was added below 0°C to adjust pH 3. The pH was maintained and slowly the temperature was raised to room temperature. Water (150 ml) was distilled out from the reaction mixture. The reaction mixture was cooled. To this reaction mass was added the slurry of azobis (amidinopropane dihydrochloride) at 50-52°C. To another reactor was charged methanol. The reaction mixture was added slowly to methanol and stirred for an hour. The reaction mixture was stopped stirring and the reaction was allowed to settle for half an hour at room temperature. The supernatant methanol was decanted. The solid was degassed till the mass became thick. Water was charged to the reaction mixture and stirred to get a clear solution. Water was distilled out and reaction mixture was cooled.
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Example 3:
In a 4 neck round bottom flask was charged polyallylamine hydrochloride solution prepared as per the process described in Example-2 (253 ml equivalent to 50g of Allyl amine). Disopropylethyl amine (50 ml) was added and the reaction mixture was stirred for an hour. Further another diisopropylethylamine (25 ml) was added and the reaction mixture was stirred for 30 mins. Another (10 ml) of Diisopropylethyl amine was added and mixture was stirred for 30 minutes. Epichlorohydrin (9.3 gm) was added to the reaction mixture and the reaction mixture was warmed to 40°C. The reaction mixture was stirred at 40°C till gel formation and then allowed to stand for further 18 hours at the same temperature. The hard gel formed was smashed and broken and transferred in to a beaker. The slurry of the same was prepared with isopropyl alcohol (650 ml) and was stirred. The reaction mixture was filtered. The gel was transferred into beaker and slurry was prepared with water (1250 ml). The process was repeated (800 ml). Stir for another hour and filter it. Gel was transferred into beaker and the slurry was prepared with isopropyl alcohol (650 ml) and the mixture was stirred and filtered. The process was repeated (400 ml). The product was suck dried well and then dried at 70 - 75°C.
Yield: 65 g
Phosphate Binding : 15.56
Example 4:
In a 4 neck round bottom flask was charged polyallylamine hydrochloride solution prepared as per Example-2 (475 ml equivalent to 100g of Allyl amine). Triethylamine (120 ml) was added and the reaction mixture was stirred for 30 minutes. Epichlorohydrin (18.6 gm) was added to the reaction mixture at room temperature and the reaction mixture was warmed to 40°C. The reaction mixture was stirred at 40°C till gel formation and then allowed to stand for further 18 hours at the same temperature. The hard gel formed was smashed and broken and transferred in a beaker. The slurry of the same was prepared with (850 ml ) Isopropyl alcohol and was stirred for 1 hr at 45-50°C. The reaction mixture was filtered. The gel was transferred into beaker and slurry was prepared with water (2000 ml). Stirred for 1 hour and filtered. The process was repeated twice (2X 2000 ml). Gel was transferred into beaker and the slurry was prepared with isopropyl alcohol(850 ml) and the mixture was stirred for lhr
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and filtered. The process was repeated again by using Isopropyl alcohol (850 ml). The product was suck dried well and then dried at 70 - 75°C.

Yield: 130g
Phosphate Binding : 15.53
Dated this 5th day of October 2007

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ABSTRACT
Title: AN IMPROVED PROCESS FOR PREPARATION OF PHOSPHATE BINDING POLYMER
The present invention relates to an improved and economical process for the manufacture of copolymer, chemically known as poly (allylamine-co-N,N'-diallyl-l,3-diamino-2-hydroxypropane) hydrochloride.
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