Title of Invention | PHARMACEUTICAL COMPOSITION CONTAINING FENOFIBRATE AND METHOD FOR THE PREPARATION THEREOF |
---|---|
Abstract | A pharmaceutical coomposition containing micronized fenofibrate, a surfactant and a binding cellulose derivative as a solubilization adjuvant fenofibrate greater than or equal to 60% by weight. |
Full Text | FORM 2 THE PATENTS ACT 1970 [39 OF 1970] & THE PATENTS (AMENDMENT) RULES 2006 COMPLETE SPECIFICATION [See Section 10; rule 13] "PHARMACEUTICAL COMPOSITION CONTAINING FENOFIBRATE AND METHOD FOR THE PREPARATION THEREOF" LABORATOIRES DES PRODUITS ETHIQUES ETHYPHARM, a French company, of 21 rue Saint-Mathieu, F-78550 Houdan, France, The following specification particularly describes the nature of the invention and the manner in which it is to be performed:- The present invention relates to a novel pharmaceutical 5 composition containing fenofibrate. Fenofibrate is recommended in the treatment of adult endogenous hyperlipidemias, of hypercholesterolemias and of hypertriglyceridemias. A treatment of 300 to 10 400 mg of fenofibrate per day enables a 20 to 25% reduction of cholesterolemia and a 40 to 50% reduction of triglyceridemia to be obtained. The major fenofibrate metabolite in the plasma is 15 fenofibric acid, The half-life for elimination of fenofibric acid from the plasma is of the order of 20 hours. Its maximum concentration in the plasma is attained, on average, five hours after ingestion of the medicinal product- The mean concentration in the plasma 20 is of the order of 15 micrograms/ml for a" dose of 300 mg of fenofibrate per day. This level is stable throughout treatment. Fenofibrate is an active principle which is very poorly 25 soluble in water, and the absorption of which in the digestive tract is limited. An increase in its solubility or in its rate of solubilization leads to better digestive absorption. 30 Various approaches have been explored in order to increase the rate of solubilization of fenofibrate: micronization of the active principle, addition of a surfactant, and comicronization of fenofibrate with a surfactant. 35 Patent EP 256 933 describes fenofibrate granules in which the fenofibrate is micronized in order tc increase its bioavailability. The crystalline fenofibrate microparticles are less than 50 µm in size, the binder used is polyvinylpyrrolidone. The document suggests other types of binder, such as methacrylic polymers, cellulose derivatives and polyethylene 5 glycols. The granules described in the examples of EP 256 933 are obtained by a method using organic solvents. IPatent EP 330 532-- proposes improving the 10 bioavailability of fenofibrate by comicronizing it with a surfactant, such as sodium lauryl sulfate. The comicronizate is then granulated by wet granulation in order to improve the flow capacities of the powder and to facilitate the transformation into gelatin capsules. 15 This comicronization allows a significant increase in the bioavailability compared to the use of fenofibrate described in EP 256 933. The granules described in EP 330 532 contain polyvinylpyrrolidone as a binder. 20 This patent teaches that the comicronization of fenofibrate with a solid surfactant significantly improves the bioavailability of the fenofibrate compared to the use of a surfactant, of micronization or of the combination of a surfactant and of micronized 25 fenofibrate. Patent WO 98/31361 proposes improving the bioavailability of the fenofibrate by attaching to a hydrodispersible inert support micronized fenofibrate, 30 a hydrophilic polymer and, optionally, a surfactant. The hydrophilic polymer, identified as polyvinyl¬pyrrolidone, represents at least 20% by weight of the composition described above. 35 This method makes it possible to increase the rate of dissolution of the fenofibrate, and also its bioavailability. However, the preparation method according to that patent is not entirely satisfactory since it requires the use of a considerable amount of PVP and of the other excipients. The example presented in that patent application refers to a composition containing only 17.7% of fenofibrate expressed as a mass ratio. This l°w mass ratio for fenofibrate leads 5 to a final form which is very large in size, hence a difficulty in administering the desired dose of fenofibrate, or the administration of two tablets. In the context of the present invention, it has been 10 discovered that the incorporation of a cellulose derivative, used as a binder and solubilization adjuvant, into a composition containing micronized fenofibrate and a surfactant makes it possible to obtain a bioavailability which is greater than for a 15 composition containing a comicronizate of fenofibrate and of a surfactant. A subject of the present invention is therefore a pharmaceutical composition containing micronized 20 fenofibrate, a surfactant and a binding cellulose derivative, which is a solubilization adjuvant, preferably hydroxypropylmethylcellulose (HPMC). The composition of the invention is advantageously 25 provided as gelatin capsules containing powder or granules, preferably in the form of granules. These granules may in particular be prepared by assembly on neutral microgranules, by spraying an aqueous solution containing the surfactant, the solubilized binding 30 cellulose derivative and the micronized fenofibrate in suspension, or by wet granulation of powder, according to which the constituents, including in particular the micronized fenofibrate, the surfactant and the cellulose derivative, are granulated by wet granulation 35 using an aqueous wetting solution, dried and calibrated. The pharmaceutical composition according to the present invention has a high proportion, of fenofibrate; it may therefore be provided in a formulation which is smaller in size than the formulations of the prior art, which makes this composition according to the invention easy to administer. 5 The amount of fenofibrate is greater than or equal to 60% by weight, preferably greater than or equal to 70% by weight, even more preferably greater than or equal to 75% by weight, relative to the weight of the 10 composition. In the context of the present invention, the fenofibrate is not comicronized with a surfactant. On the contrary, it is micronized alone and then combined 15 with a surfactant and with the binding cellulose derivative, which is a solubilization adjuvant. The surfactant is chosen from surfactants which are solid or liquid at room temperature, for example sodium 20 lauryl sulfate, Polysorbate® 80 or Montane® 20, preferably sodium lauryl sulfate. The fenofibrate/HPMC ratio is preferably between 5/1 and 15/1. 25 The surfactant represents between 1 and 10%, preferably between 3 and 5%, by weight relative to the weight of fenofibrate. 30 The binding cellulose derivative represents between 2 and 15%, preferably between 5 and 12%, by weight of the composition. Hydroxypropylmethylcellulose is preferably chosen, the 35 apparent viscosity of which is between 2.4 and 18 cP, and even more preferably between 2.4 and 3.6 cP, such as for example Pharmacoat 603®. The mean size of the fenofibrate particles is less than 15 µm, preferably 10 µm, even more preferably less than 8µm. 5 The composition of the invention may also contain at least one excipient such as diluents, for instance lactose, antifoaming agents, for instance Dimethicone® and Simethicone®, or lubricants, for instance talc. 10 The pharmaceutical composition of the invention advantageously consists of granules in an amount equivalent to a dose of fenofibrate of between 50 and 300 mg, preferably equal to 200 mg. 15 The present invention also relates to a method for preparing the powder or the granules, the composition of which is described above. This method uses no organic solvent. 20 According to a first variant, the granules are prepared by assembly on neutral microgranules. The neutral microgranules have a particle size of between 200 and 1 000 microns, preferably between 400 25 and 600 microns. The assembly is carried out in a sugar-coating pan, in a perforated coating pan or in a fluidized airbed, preferably in a fluidized airbed. 30 The assembly on neutral microgranules is carried out by spraying an aqueous solution containing the surfactant, the solubilized binding cellulose derivative, and the micronized fenofibrate in suspension. 35 According to a second variant, the granules are obtained by wet granulation of powder. The granulation enables the powders to be made dense and makes it possible to improve their flow properties. It also allows better preservation of the homogeneity, by avoiding the various constituents becoming unmixed. The micronized fenofibrate, the surfactant, the 5 cellulose derivative and, optionally, the other excipients are mixed, granulated, dried and then calibrated. The wetting solution may be water or an aqueous solution containing the binding cellulose derivative and/or the surfactant. 10 According to a particular embodiment, the fenofibrate and the other excipients are mixed in -a planetary mixer. The wetting solution is added directly to the mixture. The wet mass obtained is granulated with an 15 oscillating granulator, and then dried in an oven. The granules are obtained after passage over an oscillating calibrator. Brief Description of Accompanying Drawings. Figure 1 represents the in vivo release profile of the 20 formulation of example IC and of a formulation of the prior art in fasting individuals.Figure 2 represents the in vivo release profile of the formulation of example 1C and of a formulation of the 25 prior art in individuals who have just eaten. Figure 3 represents the in vivo release profile of the formulation of example 2B and of a formulation of the prior art in fasting individuals. 30 Figure 4 represents the in vivo release profile of the formulation of comparative example 3 and of a formulation of the prior art in individuals who have just eaten. 35 The invention is illustrated in a nonlimiting way by the following examples. Example 1: Granules 1A) Microgranules (XFEN 1735) 5 The microgranules are obtained by spraying an aqueous suspension onto neutral cores. The composition is given in the following table: Formula Amount (percentage by mass) Micronized fenofibrate Neutral microgranules HPMC (Pharmacoat 603®) Polysorbate® 80 64.5 21 11.2 3.3 Fenofibrate content 645 mg/g 10 The in vitro dissolution was determined according to a continuous flow cell method with a flow rate of 8 ml/min of sodium lauryl sulfate at 0.1 N. The percentages of dissolved product as a function of time, in comparison with a formulation of the prior art, 15 Lipanthyl 200 M, are given in the following table. Time (min) 15 30 Example 1A (% dissolved) 73 95 Lipanthyl 200 M (% dissolved) 47.3 64.7 Formulation 1A dissolves more rapidly than Lipanthyl 200 M. 20 1B) Microgranules (X FEN 1935) The mean size of the fenofibrate particles is equal to 6.9 ± 0.7 microns. 25 The microgranules are obtained by spraying an aqueous suspension onto neutral cores. The suspension contains micronized fenofibrate, sodium lauryl sulfate and HPMC. The assembly is carried out in a Huttlin fluidized airbed (rotoprocess). The formula obtained is given below. FORMULA AMOUNT (percentage by mass) Micronized fenofibrate Neutral microgranules HPMC (Pharmacoat 603®) Sodium lauryl sulfate 65.2 20.1 11.4 3.3 Fenofibrate content 652 mg/g The size of the neutral microgranules is between 400 and 600 urn. 10 1C) Gelatin capsules of microgranules (Y FEN 001) Microgranules having the following composition are prepared: RAW MATERIALS AMOUNT (percentage by mass) Micronized fenofibrate Neutral microgranules Pharmacoat 603® (HPMC) Sodium lauryl sulfate 35% dimethicone emulsion Talc 67.1 17.2 11.7 3.3 0.2 0.5 Fenofibrate content 671 mg/g 15 according to the method described in paragraph 1A). The microgranules obtained are distributed into size 1 gelatin capsules, each containing 200 mg of 20 fenofibrate. The in vitro dissolution is determined according to a continuous flow cell method with a flow rate of 8 ml/min of sodium lauryl sulfate at 0.1 N. The comparative results with a formulation of the prior art, Lipanthyl 200 M, are given in the following table. Time (min) 15 30 Example 1C (% dissolved) 76 100 Lipanthyl 200 M (% dissolved) 47.3 64.7 Formula 1C dissolves more rapidly than Lipanthyl 200 M. 5 The gelatin capsules are conserved for 6 months at 40°C/75% relative humidity. The granules are stable under these accelerated storage conditions. In vitro dissolution tests (in continuous flow cells with a flow 10 rate of 8 ml/min of sodium lauryl sulfate at 0.1 N) were carried out. The percentages of dissolved product as a function of time for gelatin capsules conserved for 1, 3 and 6 months are given in the following table. Dissolution time (min) Conservation time 1 month (% dissolved product) 3 months (% dissolved product) 6 months (% dissolved product) 5 15 25 35 45 55 65 25.1 71.8 95.7 104.7 106.4 106.7 106.8 23.0 65.6 88.7 98.7 100.2 100.5 100.6 20.1 66.5 91.0 98.2 99.1 99.5 99.7 1 The evolution of the content of active principle during storage is given in the following table. Content (mg/gelatin Capsule) Conservation time 0 1 month 3 months 6 months 208.6 192.6 190.8 211.7 Pharmacokinetic study carried out in fasting individuals The in vivo release profile of the gelatin capsules 5 containing the YFEN 01 granules at a dose of 200 mg of fenofibrate is compared with that of the gelatin capsules marketed under the trademark Lipanthyl 200 M. This study is carried out in 9 individuals. Blood 10 samples are taken at regular time intervals and fenofibric acid is assayed. The results are given in the following table and figure 1. Pharmacokinetic Lipanthyl 200 M Example 1C parameters AUC0-t 76 119 (µg.h/ml) AUCinf 96 137 (µg.h/ml) Cmax 2.35 4.71 (µg/ml) Tmax 8.0 5.5 (hours) Ke 0.032 0.028 (1/hour) Elim 1/2 26.7 24.9 (hours) The following abbreviations are used in the present application: 20 Cmax"* maximum concentration in the plasma, Tmax: time required to attain the Cmax, Elim 1/2: plasmatic half-life, AUC0-t: area under the curve from 0 to t, AUC0-oo: area under the curve from 0 to 00, 25 Ke: Elimination constant. The results obtained for Lipanthyl 200 M and for the product of example 1C are represented on figure 1 by curves 1 and 2, respectively. 5 These results show that the composition according to the present invention has a bioavailability which is greater than that of Lipanthyl 200 M in fasting individuals. 10 Pharmacokinetic study carried out in individuals who have just eaten The in vivo release profile of the gelatin capsules containing the YFEN 01 granules at a dose of 200 mg of 15 fenofibrate is compared with that of the gelatin capsules marketed under the trademark Lipanthyl 200 M. This study is carried out in 18 individuals. Blood samples are taken at regular time intervals and 20 fenofibric acid is assayed. The results are given in the following table and figure 2. Pharmacokinetic Lipanthyl 200 M Example 1C parameters AUC0-t 244 257 (µg.h/ml} AUCinf 255 270 (µg.h/ml) Cmax 12 13 (ug/ml) Tmax 5.5 5.5 (hours) Ke 0.04 0.04 (1/hour) Elim 1/2 19.6 19.3 (hours) The results obtained for Lipanthyl 200 M and for the product of example 1C are represented on figure 2 by curves 1 and 2, respectively. 5 These results show that the composition according to the present invention is bioequivalent to that of Lipanthyl 200 M in individuals who have just eaten. Example 2: Powder 0 2A) Granules (X FEN 1992) Granules having the following composition are prepared FORMULA PERCENTAGE BY MASS Micronized fenofibrate 71 Lactose 21.5 HPMC (Pharmacoat 603®) 5 Sodium lauryl sulfate 2.5 The micronized fenofibrate, the HPMC and the lactose are mixed using a planetary mixer. This mixture is granulated in the presence of a solution of sodium lauryl sulfate. 20 The flow time of the granules is 7 s. The compacting capacity and the particle size distribution are given in the following tables. These measurements were carried out in accordance with the standards of the 25 European Pharmacopoeia. Compacting capac ity (X FEN 1992) v0 204 ml V10 186 ml V500 168 ml V1250 164 ml V10-V500 22 ml Particle size distribution (X FEN 1992) Sieve mesh size % of oversize mass (mm) 0.6 8 0.5 9 0.355 12 0.2 30 ■ 0.1 23 0 18 2B) Gelatin capsules of granules (Y FEN 002) 5 • Preparation The micronized fenofibrate is mixed in a PMA mixer (Niro Fielder) with lactose and HPMC, and then wetted with an aqueous solution of sodium lauryl sulfate. The 10 mass obtained is granulated by passage over an oscillating granulator, dried and then calibrated on a sieve with a mesh size of 1.25 mm. The granules are then packaged in size 1 gelatin 15 capsules at doses of 200 mg of fenofibrate. Granules of the following composition are obtained. FORMULA PERCENTAGE BY MASS Micronized fenofibrate Lactose Pharmacoat 603® (HPMC) Sodium lauryl sulfate 70 21.5 5 3.5 Content 700 mg/g 20 • Properties of the granules The flow time of the granules is 6 s. The compacting capacity and the particle size distribution are given in the following tables. These measurements were carried out in accordance with the standards of the European Pharmacopoeia. Compacting capacity (Y FEN 002) V0 216 ml V10 200 ml V500 172 ml V1250 170 ml V10-V500 28 ml 5 Particle size distribution (Y FEN 002) Sieve mesh size % of oversize mass (mm) 0.6 5 0.5 7 0.355 11 0.2 30 0.1 25 0 22 The in vitro dissolution is determined according to a continuous flow cell method with a flow rate of 8 ml/min of sodium lauryl sulfate at 0.1 N. The 10 comparative results for a formulation of the prior art, Lipanthyl 200 M, are given in the following table. Time (min) 15 30 Example 2B (% dissolved) 82.2 88.5 Lipanthyl 200 M (% dissolved) 47.3 64.7 Formulation 2B dissolves more rapidly than 15 Lipanthyl 200 M. • Stability tests The gelatin capsules conserved at 40°C/75% relative 20 humidity are stable for 6 months. In vitro dissolution tests (in continuous flow cells with a flow rate of 8 ml/min of sodium lauryl sulfate at 0.1 N) were carried out. The percentages of dissolved product as a function of time for gelatin 5 capsules conserved for 1, 3 and 6 months are given in the following table. Dissolution time (min) Conservation time 1 month (% dissolved product) 3 months (% dissolved product) 6 months (% dissolved product) 5 15 25 35 45 55 65 54.2 81.1 86.4 88.8 90.7 92.1 93.2 52.9 75.8 79.6 81.6 82.9 83.9 84.7 49.0 82.2 87.2 89.8 91.5 92.7 93.6 The evolution of the content of active principle during 10 storage is given in the following table. Content (mg/gelatin capsule) Conservation time 0 1 month 3 months 6 months 196.6 190.0 199.8 203.3 Pharmacokinetic study carried out in fasting individuals 15 The in vivo release profile of the gelatin capsules containing the YFEN 002 granules at doses of 200 mg of fenofibrate is compared with that of the gelatin capsules marketed under the trademark Lipanthyl 200 M. 20 This study is carried out in 9 individuals. Blood samples are taken at regular time intervals and fenofibric acid is assayed. The results are given in the following table and figure 3. Pharmacokinetic Lipanthyl 200 M Example 2B parameters AUCo-t 76 70 (ug.h/ml) AUCinf 96 82 (µg.h/ml) Cmax 2.35 .2.8 (ug/ml) Tmax 8.0 5.5 (hours) Ke 0.032 0.033 (1/hour) Elim 1/2 26.7 23. 1 (hours) J 5 The results obtained for Lipanthyl 200 M and for the product of example 2B are represented on figure 3 by curves 1 and 2, respectively. These results show that the composition of example 2B 10 is bioequivalent to that of Lipanthyl 200 M in fasting individuals. Comparative example 3: batch 2EF 001 15 This example illustrates the prior art. It combines micronization of fenofibrate and the use of a surfactant. It differs from the present invention by the use of the mixture of binding excipients consisting 20 of a cellulose derivative other than HPMC: Avicel PH 101 and polyvinylpyrrolidone (PVP K30). It is prepared by extrusion-spheronization. Theoretical formula Products Theoretical amount (%) Micronized fenofibrate 75.08 Montanox 80® 4.72 Avicel PH 101® 5.02 PVP K 30® 4.12 Explotab® 11.06 * In vitro dissolution profile 5 The in vitro dissolution is determined according to a continuous flow cell method with a flow rate of 8 ml/min of sodium lauryl sulfate at 0.1 N. The comparative results with Lipanthyl 200 M are given in 10 the following table. Time (min) 15 30 Example 3 (% dissolved) 24 40 Lipanthyl 200 M (% dissolved) 47.3 64.7 The dissolution is slower than that observed for Lipanthyl 200 M. 15 Pharmacokinetic study carried out in fasting individuals The in vivo release profile of the gelatin capsules 20 containing the ZEF 001 granules at doses of 200 mg of fenofibrate is compared with that of the gelatin capsules marketed under the trademark Lipanthyl 200 M. This study is carried out in 5 fasting individuals 25 receiving a single dose. Blood samples are taken at regular time intervals and fenofibric acid is assayed. The results are given in the following table and figure 4. 30 Pharmacokinetic Lipanthyl 200 M Example 3 parameters AUCo-t 92 47 (µg.h/ml) AUCinf 104 53 (µg.h/ml) Cmax 3.5 1.7 (µg/ml) Tmax 5.6 4.6 (hours) Ke 0.04 0.038 (1/hour) Elim 1/2. 18.9 20.3 (hours) The results obtained for Lipanthyl 200 M and for the product of example 3 are represented on figure 4 by 5 curves 1 and 2, respectively. These results show the greater bioavailability of Lipanthyl 200 M compared with this formulation based on the prior art. 10 Example 3 shows that combining the knowledge of the prior art (namely micronization or use of surfactants) does not make it possible to obtain rapid dissolution of fenofibrate. This results in low bioavailability 15 compared with Lipanthyl 200 M. The compositions prepared according to the present invention show more rapid dissolution than the formula of the prior art and improved bioavailability. 20 WE CLAIM: 1. A pharmaceutical composition in the form of granules, wherein each granule comprises a neutral microgranule on which is a composition comprising: micronized fenofibrate, a surfactant, and a binding cellulose derivative as a solubilization adjuvant, and wherein said fenofibrate is present in an amount greater than or equal to 60% by weight, relative to the weight of said pharmaceutical composition, and further wherein said binding cellulose derivative represents between 2 to 15% by weight, relative to the weight of said pharmaceutical composition. 2. The composition as claimed in claim 1, wherein the binding cellulose derivative which is a solubilization adjuvant, is hydroxypropylmethylcellulose. 3. The composition as claimed in claim 2, wherein the hydroxypropylmethylcellulose has an apparent viscosity of between 2.4 and 18 cP, preferably of between 2.4 and 3.6 cP. 4. The composition as claimed in one of claims 1 to 3, wherein it contains an amount of fenofibrate, greater than or equal to 70% by weight, even more preferably greater than or equal to 75% by weight, relative to the weight of the composition. 5. The composition as claimed in one of the preceding claims, wherein the surfactant is chosen from the group made up of polysorbate® 80, Montane® 20 and sodium lauryl sulfate. 6. The composition as claimed in claim 1, wherein said surfactant represents between 3 and 5 % by weight relative to the weight of fenofibrate. 7. The composition as claimed in one of claims 2 to 5, wherein the fenofibrate/HPMC mass ratio is between 5/1 and 15/1. 8. The composition as claimed in one of the preceding claims, wherein the binding cellulose derivative represents between 5 and 12%, by weight of the composition. 9. The composition as claimed in one of the preceding claims, wherein it contains at least one excipient such as a diluent, for instance lactose, an antifoaming agent, for instance Dimethicone® or Simethicone®, or a lubricant, for instance talc. 10. The composition as claimed in one of the preceding claims, wherein the mean size of the fenofibrate particles is less than 15 µm, preferably less than 8 µm. 11. The composition as claimed in one of the preceding claims, wherein it is in the form of gelatin capsules containing powder or granules. 12. A method for preparing the composition as claimed in one of the preceding claims, wherein granules are prepared by assembly on neutral microgranules, by spraying an aqueous suspension containing the surfactant, the solubilized binding cellulose derivative and the micronized fenofibrate in suspension. 13. The method for preparing the composition as claimed in one of claims 1 to 10, wherein granules are obtained by wet granulation of powder, according to which the constituents, including in constituents, including in particular the micronized fenofibrate, the surfactant and the cellulose derivative, are granulated by wet granulation using an aqueous wetting solution, dried and calibrated. Dated this January 08, 2002. (DEEPAK KUMAR) OF REMFRY AND SAGAR ATTORNEY FOR THE APPLICANTS |
---|
in-pct-2002-00025-mum-cancelled pages(24-09-2007).pdf
in-pct-2002-00025-mum-claims(granted)-(24-09-2007).doc
in-pct-2002-00025-mum-claims(granted)-(24-09-2007).pdf
in-pct-2002-00025-mum-correspondence(04-10-2007).pdf
IN-PCT-2002-00025-MUM-CORRESPONDENCE(2-2-2012).pdf
in-pct-2002-00025-mum-correspondence(ipo)-(04-10-2006).pdf
in-pct-2002-00025-mum-drawing(24-09-2007).pdf
IN-PCT-2002-00025-MUM-ENGLISH TRANSLATION(2-2-2012).pdf
in-pct-2002-00025-mum-form 1(08-01-2002).pdf
in-pct-2002-00025-mum-form 1(24-09-2007).pdf
in-pct-2002-00025-mum-form 13(01-10-2007).pdf
in-pct-2002-00025-mum-form 13(24-09-2007).pdf
in-pct-2002-00025-mum-form 18(22-12-2005).pdf
in-pct-2002-00025-mum-form 2(granted)-(24-09-2007).doc
in-pct-2002-00025-mum-form 2(granted)-(24-09-2007).pdf
in-pct-2002-00025-mum-form 3(08-01-2002).pdf
in-pct-2002-00025-mum-form 3(24-09-2007).pdf
in-pct-2002-00025-mum-form 5(08-01-2002).pdf
in-pct-2002-00025-mum-form-pct-ipea-409(08-01-2002).pdf
in-pct-2002-00025-mum-form-pct-isa-210(08-01-2002).pdf
in-pct-2002-00025-mum-petition under rule 137(22-09-2007).pdf
in-pct-2002-00025-mum-petition under rule 138(24-09-2007).pdf
in-pct-2002-00025-mum-power of authority(13-12-2001).pdf
in-pct-2002-00025-mum-power of authority(24-09-2007).pdf
Patent Number | 221507 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Indian Patent Application Number | IN/PCT/2002/00025/MUM | ||||||||||||
PG Journal Number | 35/2008 | ||||||||||||
Publication Date | 29-Aug-2008 | ||||||||||||
Grant Date | 24-Jun-2008 | ||||||||||||
Date of Filing | 08-Jan-2002 | ||||||||||||
Name of Patentee | LABORATOIRES DES PRODUITS ETHIQUES ETHYPHARM | ||||||||||||
Applicant Address | 21 RUE SAINT-MATHIEU, F-78550 HOUDAN, FRANCE | ||||||||||||
Inventors:
|
|||||||||||||
PCT International Classification Number | A 61 K 9/14 | ||||||||||||
PCT International Application Number | PCT/FR00/01971 | ||||||||||||
PCT International Filing date | 2000-07-07 | ||||||||||||
PCT Conventions:
|