Title of Invention	PROCESS FOR THE PREPARATION OF GRANULES OF METHIONINE
Abstract	A process for the preparation of granules of methionine which process comprises (a) applying the mixture to high shear rate mixing, thereby forming granules of said mixture; and (c) drying said grnules.

Full Text

FORM 2 THE PATENTS ACT 1970 [39 OF 1970] & THE PATENTS (AMENDMENT) RULES 2006 COMPLETE SPECIFICATION [See Section 10; rule 13] "PROCESS FOR THE PREPARATION OF GRANULES OF METHIONINE" ADISSEO FRANCE S.A.S., a French company of 42 avenue Aristide Briand, 92160 Antony, France, The following specification particularly describes the nature of the invention and the manner in which it is to be performed :- original 135/mumnp/2003 12-8-2007 WO 02/41555 PCT/EP01/09877 PROCESS FOR THE PREPARATION OF GRANULES OF METHIONINE The present invention relates to a process for the preparation of free 5 flowing granules of methionine suitable for use as an animal feed supplement. Methionine is used as a feed additive for animals, in particular ruminants and poultry, and is useful in the production of animal proteins. Methionine is produced by the conversion of methionine nitrile to methionine amide, followed by saponification of the amide. The resulting methionine product is a fine powder 10 and a problem encountered on the production plant is the presence of static electricity, providing a high risk of explosion. To overcome this problem, the powdered methionine is recrystallised. This involves an additional step in the process. The recrystallised methionine may then be used in this form as the feed supplement. 15 An alternative means to overcome this problem is disclosed in European Patent No. 0992490 in which the powdered methionine is converted to granules. This method comprises forming extrudates from the powdered methionine, and then treating the extrudates to provide substantially spherical particles. EP-A-0992490 purports to provide a method of producing granules of methionine for 20 use in animal feed which avoids the problem of dust and ultimate risk associated with static electricity. We have developed a process for the production of granules of methionine that produces directly the spherical granules of methionine without the need for the additional step of treating the granules to obtain the desired spherical 25 shape. Accordingly, the present invention provides a process for the preparation of granules of methionine which process comprises (a) forming a mixture of methionine powder, a binding agent and water (b) applying the mixture to high shear rate mixing, thereby forming granules of said mixture; and (c) drying said 30 granules. The process of the present invention negates the need to shape the product. We have also found that the resulting granules have specific advantageous properties that render them particularly suitably for incorporation into animal feed, in particular good mixability. 2 WO 02/31555 " PCT/EP01/09877 For the purposes of the present invention, "methionine powder" is defined as particles of methionine in which less than 40% of the particles have a size greater than 150 microns. In particular, it is preferred that less than 10% of the particles are greater than 150 microns and that the powder has a bulk density 5 of from 300 to 500 kg/m3 and a tapped density of from 500 to 600 kg/m3. The process of the present invention comprises a first step of forming a mixture of methionine powder, a binding agent and water. The methionine powder may be used as is, in the solid form, or may be used as a suspension of methionine in water. Suitably, the mixture comprises from 30 to 82 weight %, 10 preferably from 55 to 80 weight % methionine. Suitable binding agents for inclusion into the mixture include celluloses, for example, microcrystalline cellulose, hydroxypropyl methyl cellulose and carboxyl methyl cellulose; starch for example native, pregelatmized or modified starch; hydrocolloid gums, for example, xanthane gum, guar gum, carob gum and 15 arabic gum; polyvinyl alcohol; polyvinyl pyrrolidone; sugars and syrup of sugars, for example a mixture of oligo and polysaccharides. The preferred binder is a starch or a hydrocolloid gum, especially xanthane or arabic gum. Suitably, the binder is present in the mixture in an amount of from 0.3 to 10 % by weight, preferably from 0.5 to 5% by weight. The binder may be added in the solid form 20 or in the liquid form, especially as an aqueous solution. Water may be admixed with the other components before application of the high shear rate mixing or may be added during the high shear mixing. Water may be present in the mixture in an amount of from 15 to 65 % by weight, preferably from 15 to 40 % by weight. 25 Additional components may be present in the mixture. A surfactant may be added to the mixture. Suitable surfactants include non ionic surfactants such as polyoxyethylene sorbitan fatty acid esters 20 to 80 or anionic surfactants such as dodecyl sodium sulphonate. The surfactant may be present in an amount of from 0 to 1.5 % by weight, preferably from 0.1 to 1 % by weight. 30 Certain salts that are known to have an efficacious effect in animals may also be present in the mixture. The salt may be added as a separate component prior to the high shear rate mixing. Alternatively, the salt may be present as an admixture with the methionine powder and may be granulated with the methionine powder. In such case, the methionine powder may be used directly 35 from the production method which can comprise a mixture of methionine and a 3 WO .02/11555 PCT/EP01/09877 salt, the salt having been co-formed during the saponification step. In particular, metal salts of Group I or II of the Periodic Table, for example, sodium or potassium, especially sodium, may be present with the methionine powder. Suitable salts are halides such as sodium chloride, sulphates such as sodium 5 sulphate and the methioninate salt such as sodium methioninate. Suitably, the salt may be present in the mixture in an amount of from 0 to 30 %, preferably from 10 to 20% by weight. Further nutritionally active compounds may also be present, for example amino acids such as lysine and vitamins such as Vitamin A and Vitamin E. Such 10 compounds may be present in the mixture in an amount of from 0 to 20 weight %. The second step of the process of the present invention involves high shear rate mixing of the mixture to form the granules. The mixing is carried out using any suitable apparatus that is capable of providing the necessary mixing, for example, high shear and high speed mixers, especially an impeller mixer in which 15 the mixture is centrifuged against the walls of the mixer chamber. The speed of the mixer will depend upon the size and capacity of the mixer. The mixing is suitably carried out at a speed of at least 5 ms1, preferably between 30 and 80 ms" This granulation step may be carried out at ambient or elevated temperature, preferably at ambient temperature. 20 The resulting granules are then dried, preferably using a fluidised bed drier at a temperature of up to 150°C, preferably between 20 and 150°C. The aforementioned processes may be carried out as a continuous process or as a batch process. The granule produced from this granulation process has a substantially 25 spherical shape and, thus, does not require further treatment. A particular advantage of the granule produced by the method of the present invention is that the granule has a bulk density similar to the resulting pellet of animal feed to which the methionine granule is to be incorporated. The resulting methionine granule also exhibits good mixability in the animal feed. In particular, it has been 30 found that the method of the present invention provides granules of methionine having a bulk density of at least 0.6g/cm3, preferably at least 0.7g/cm3, this being in the same region as the density of the animal feed pellets. Thus, according to another aspect of the present invention there is provided granules of methionine prepared as hereinbefore defined having a bulk density of at least 0.6g/cm3. 4 WO 02/11555 PCT/EP01/09877 The granules of methionine suitably have a particle size distribution of from 50 to 2000 microns, preferably from 100 to 1500 microns, especially from 200 to 1200 microns, with less than 10% of the granules being less than 200 microns and less than 10% greater than 1000 microns. 5 The granules of methionine produced by the process of the present invention suitably contain from 65 to 98 % methionine, 0.3 to 12 % binding agent, less than .1% water and from.O to 1.7 % by weight surfactant When a salt is present in the mixture, the ratio of methionine to salt suitably is from 0.7 to 1. In particular, we have found that granules of methionine comprising 10 sodium chloride, have a bulk density of at least 0.7g/cm3 and the particle size distribution is of from 100 microns to 2000 microns, preferably from 400 to 1500 microns. The granules of methionine may be used as an animal feed supplement and thus according to a further aspect of the present invention there is provided an 15 animal feed composition comprising granules of methionine as hereinbefore defined. The invention will now be illustrated with reference to the following examples: Examples 1 to 7 exemplify the preparation of the granules of methionine 20 according to the present invention. Comparative Examples A to D exemplify the preparation of granules according to the prior art method. In Examples 1 to 7, the following equipment was used: A Fryma Diosna mixer of 30 litres capacity A Retsch TG-1 fluidised bed dryer. 25 In comparative Examples A to D the following equipment was used: A Lodige blender of 5 litres capacity A Fuji Paudal DG-L1 extruder (flow .5 to 50 kg/hour) A Retsch TG-1 fluidised bed dryer To evaluate the properties of the granules the following standard tests 30 were carried out: (1) Water Content - The amount of water was determined by infra red balance at 105°C until constant weight. (2) Granule Size - The size of the granule was measured by passing l00g of granules through Retsch sieves with 1.5 mm of amplitude for 10 35 minutes. 5 WO 02/11555 PCT/EPO1/09877 (3) Bulk and Tapped Density - The bulk and tapped density were measured by powder volumenometer (230 nil). (4) Carr Index - Defined as: (Bulk Density - Tapped Density) / Bulk Density. (5) The Jenike Index was measured by a flow tester which is the ring shear stress of Schulze (device referenced RST-01.01 Dr Ing. Dietmar Schulze, Wolfenbuttel, Germany). Jenike Index is defined by the ratio of principal stress at a steady flow to the unconfined yield strength. 10 Granules of methionine, as detailed in Examples 1 to 7, were prepared according to the following procedure: Step (1): The powdered methionine, binder and water were added to the mixer operating at a stirring speed of 6 ms"1 The stirring was continued for 10 minutes. 15 Step (2) : Where a surfactant was used, the surfactant powder was dissolved with stirring in water at ambient temperature until a homogeneous solution was obtained. The surfactant solution was sprayed into the blender using a nozzle operating at a liquid flow between 3.6 and 10 kg/h. The spraying was continued for 10 minutes. The crushing turbine was then operated for 30 minutes. 20 Step (3): The resulting granules were dried at 40°C for 60 minutes. Example 1: Powdered methionine, starch binding agent, water and a surfactant were used in the following amounts: 25 Table 1 Component Concentration of Component (%) Concentration in dry granule (%) Weight (g) powdered methionine 81.28 97.85 2450.0 pregeletanised starch o.so 0.97 24.2 surfactant 0.15 0.18 4.6 water 17.76 1.00 535.3 total 100.00 100.00 3014.1 The concentration of surfactant in water was 0.8%. 6 WO 02/11555 " PCT/EP01/09877 The ratio ofmethonine to binder was 1%. The resulting granules have a mean diameter D50 equal to 608 microns with 10% 1 mm. The bulk density was 0.650 g/cm3, the tapped"density was 0.720 g/cm3, the Carr Index was 11% and the Jenilce Index 5 was 23. Example 2: The procedure of Example 1 was repeated but the binding agent was introduced as a mix with the surfactant in an aqueous solution at 4.6 10 kg/h. Table 2 Component Concentration of Component (%) Concentration in dry granule (%) Weight (g) powdered methionine 81.28 97.85 2000.0 pregelatinised starch 0.80 0.97 19.7 surfactant 0.15 0.18 3.7 water 17.76 1.00 437.0 total 100.00 100.00 2460.4 The concentration of surfactant in water was 0.85%. 15 The ratio of memionine to binder was 1 %. The granules had D50 equal to 610 microns with 13% less than 200 microns and 5% greater than 1000 microns. The bulk density was 0.643 g/cm3, the tapped density was 0.704 g/cm3, the Carr Index was 9.5%. 20 25 7 WO 02/11555 PCT/EP01/09877 Example 3 : The procedure of Example 1 was repeated but varying the amount of starch and with the following amounts of components: Table 3 Component Concentration of Component (%) Concentration in dry granule (%) Weight (g) powdered methionine 80.18 96.82 2000.0 pregeletanised starch 1.60 1.96 40.0 surfactant 0.18 0.22 4.5 water 18.04 1.00 450.0 Total 100.00 100.00 2494.5 The concentration of surfactant in water was 1 %. The ratio of methionine to binder was 2%. The resulting granules had D50 equal to 930 microns with 1% microns and 40% > 1 mm. The bulk density was 0.68g/crn3, the tapped density 10 was 0.74g/cm3 and the Carr Index was 8%. Example 4 : The procedure of Example 1 was repeated varying the amount of starch and with the following amounts of components: 15 Table 4 Component Concentration of Component (%) Concentration in dry granule (%) Weight (g) powdered methionine 78.00 94.12 2980.0 pregeletanised starch 3.90 4.76 149.0 surfactant 0.10 0.12 3.7 water 18.00 1.00 688.0 total 100.00 100.00 3820.7 The concentration of surfactant in water was 0.5 %. The ratio of methionine to binder was 5%. 8 WO 02/11555 PCT/EP01/09877 The resulting granules had D50 equal to 1 mm with 1% Example 5. : The procedure of Example 1 was repeated but replacing the starch with xanthane gum and with the following amounts of components: Table 5 Component Concentration of Component (%) Concentration in dry granule (%) Weight (g) powdered methionine 79.02 97.76 1700.0 xanthane gum 0.79 0.99 17.0 surfactant 0.20 0.25 ■-4.3 water 19.99 1.00 430.0 total 100.00 100.00 2151.3 The concentration of surfactant in water was 1%. The ratio of methionine to binder was 1%. The resulting granules had a medium diameter D50 equal to 1 mm with 5% of the granules less than 200 microns. The bulk density was 0.610 g/cm3and the tapped density was 0.670 g/cm3 and the Carr Index was 10%. WO 02/11555 PCT/EP01/09877 Example 6 : The procedure of Example 1 was repeated varying the amount of starch and including a salt and with the. following amounts of components". Table 6 Component Concentration of Component (%) Concentration in dry granule (%) Weight (g) powdered methionine . 71.30 82.16 1700.0 sodium chloride 12.58 14.68 300.0 pregelatinised starch 1.68 1.96 40.0 surfactant 0.18 0.20 4.2 water 14.26 1.00 340.0 total 100.00 100.00 2384.2 In this example, the sodium chloride salt was added to the blender with the powdered methionine and the binder. The concentration of surfactant in water was 1.2 %. The ratio of methionine to binder was 2.35%. 10 The resulting granules had D50 equal to 430 microns with 17% microns and 5% > 1mm. The bulk density was 0.716 g/cm3, the tapped density was 0.770 g/cm3 and the Carr Index was 8%. The Jenike Index was 16.5. Example 7 : The procedure of Example 6 was repeated varying the 15 amount of salt and with the following amounts of components: Table 7 Component Concentration of Component (%) Concentration in dry granule (%) Weight (g) powdered methionine 63.19 71.33 1700.0 sodium chloride 22.30 25.53 600.0 pregelatinised starch 1.72 1.96 46.2 surfactant 0.16 0.18 4.2 water 12.63 1.00 340.0 total 100.00 100.00 2690.4 10 WO 02/11555 PCT/EP01/09877 The concentration of surfactant in water was 1.2 %. The ratio of methionine to binder was 2.7%. The resulting granules had D50 equal to 570 microns with 5% > 1mm and 11% Comparative Examples : Granules of metinonine were prepared by the extrusion method according to the following steps: Step (1) ; The binder was dissolved, with stirring, in water at ambient temperature until a homogeneous solution (2% w/w) was obtained. Step (2) : The temperature of the blender was set at 60° C. The powdered metliionine was placed in the blender operating at a stirring speed of 2 minutes per second. The binder solution prepared in Step (1) was then added at a rate of 500 grams per minute and the resulting mixture was stirred until a paste was formed. The paste was then left to cool to ambient temperature. Step (3) : The paste was placed in the extruder which was fitted with a 0.7 mm size grid. The extrudate material was transferred to the fluidised bed dryer where the granules were left to dry at ambient temperature for 60 minutes, followed by a further 60 minutes at 60°C. Comparative Example A Comparative to Example 1 Powdered methionine, starch binding agent and water were used in the following amounts: Table A Component Concentration of Component (%) Concentration in dry granule (%) Weight (g) powdered methionine 73.98 98.00 600.0 pregeletanised starch 0.75 1.00 6.1 water 25.27 1.00 204.9 total 100.00 100.00 811.0 11 wVO 02/11555 PCT7EP01/09877 The concentration of starch in solution was 3 %w/w. 75% of the granules had a size distribution of between 200 and 1000 microns with 5% greater than 1000 microns and 20% less that 200 microns. The bulk density and tapped density were determined to be 0.470 g/cm3 and 0.620 5 g/cm3 respectively. The Carr Index was 15%. Comparative Example B : Comparative example to Example 4 10 The procedure of Comparative Example A was repeated using a cellulose binder and with the following amounts of components. Table B Component Concentration of Component (%) Concentration in dry granule (%) Weight (g) ! powdered rnethionine 69.93 95.92 400.0 pregelatinised starch 2.97 4.08 17.0 water 27.10 1.00 155.0 total 100.0 100.00 572.0 The extruder was fitted with a 1 mm grid and the concentration of 15 cellulose in solution was 11 %w/w. 80% of the granules had a size distribution of between 500 and 1600 microns with 20% less than 500 microns. The bulk density and tapped density were determined to be 0.420 g/cm3 and 0.530 g/cm3 respectively. The Carr Index was determined to Toe 26%. 20 25 12 wVO 02/11555 PCT/EP01/09877 Comparative Example C: Comparative to Example 5 The procedure of Comparative Example A was repeated using a xanthane gum as binder and with the following amounts of components. Table C Component Concentration of Component (%) Concentration in dry granule (%) Weight (g) powdered methionine 70-55 98.58 400.0 xanthane gum 0.30 0.42 1.7 water 29.15 1.00 165.3 Total 100.00 100.00 567.0 The concentration of xanthane gum in solution was 1 %w/w. 97% of the granules had a size distribution of between 200 and 1600 microns with 3% greater that 1600 microns and 3% less than 200 microns. The bulk density and tapped density were determined to be 0.540 g/cm3 and 0.610 g/cm3 respectively. The Carr Index was determined to be 13%. Comparative Example D: Comparative to Example 7 The procedure of Example A was repeated but with the addition of sodium chloride salt and with the following amounts of components. Table D Component Concentration of" Component (%) Concentration in dry granule (%) Weight (g) powdered methionine 52.00 68.33 416.0 pregelatinised starch 0.50 0.67 4.0 sodium chloride 22.50 30.0 180.0 water 25.00 1.00 200.0 total 100.00 100.00 800.0 13 WO 02/11555 PCT/EP01/09877 The concentration of starch in solution was 2 %w/w. 60% of the granules had a size distribution of between 200 and 1000 microns with 26% greater that 1000 microns and 14% less than 200 microns. The bulk density and tapped density were determined to be 0.570 g/cm3 and 0.640 5 g/cm3 respectively. The Carr Index was determined to be 12%. It can be seen from these examples that the process of the present invention provides granules with greater bulk density than the extrusion method. 10 14 WE CLAIM: 1. A process for the preparation of granules of methionine which process comprises (a) forming a mixture of methionine powder, a binding agent selected from cellulose, starch, hydrocolloid gum, polyvinyl alcohol, polyvinyl pyrrolidone, sugar and syrup of sugar and water (b) applying the mixture to high shear rate mixing, at a speed of least 5 ms4, at ambient or elevated temperature, thereby forming granules of said mixture; and (c) drying said granules. 2. A process as claimed in claim 1 where the granulation is carried out in a high shear and high speed mixer wherein the mixture is centrifuged against the walls of the mixer. 3. A process as claimed in claim 1 or claim 2 wherein the methionine powder is having a bulk density of from 300 to 500 kg/m3 and a tapped density of from 500 to 600 kg/m3 and a particle size distribution wherein at least 40 % of the particles of methionine have size greater than 150 microns. 4. A process as claimed in any one of the preceding claims wherein the mixture comprises 30 to 82 % by weight methionine powder, 0.3 to 10 % by weight binding agent and 15 to 65 % by weight water. 5. A process as claimed in any one of the preceding claims wherein the mixture comprises a surfactant selected from non ionic surfactants and anionic surfactants. 15 6. A process as claimed in any one of the preceding claims wherein the mixture comprises a salt of metals selected from Group I or II of the Periodic Table. 7. A process as claimed in claim 6 wherein the salt is sodium chloride or sodium methioninate. 8. A process as claimed in any one of the preceding claims wherein said process is carried out continuously or batch. Dated this 29th day of January, 2003 (DEEPAK KUMAR) OF REMFRY & SAGAR ATTORNEYS FOR THE APPLICANTS 16

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