Title of Invention

STABLE ORAL DOSAGE COMPOSITIONS OF BISPHOSPHONIC ACIDS

Abstract A stabilized oral dosage pharmaceutical composition of bisphosphonic acid derivative comprising at least one carbohydrate alcohol, which do not contain a reducing aldehyde moiety, together with an aqueous binder; wherein said composition is devoid of lactose.
Full Text FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
COMPLETE SPECIFICATION
[See section 10, rule 13]
"Stable oral dosage compositions of bisphosphonic acids"
(a) CIPLALTD.
(b) 289, Bellasis Road, Mumbai Central, Mumbai - 400 008, Maharashtra, India
(c) Indian Company incorporated under the Companies Act 1956
The following specification describes the nature of this invention and the manner in which it is to be performed:


Technical field
The present invention relates to an improved, stable oral formulation comprising bisphosphonacid derivatives, its process of manufacture and use thereof.
Background and prior art
Bisphosphonic acid derivatives are very well known to be used for treatment of skeletal disorders. These bisphosphonic acids include but are not limited to clodronic acid, pamidronic acid, alendronic acid, risedronic acid, etidronic acid, ibandronaic acid, tiludronic acid such other compounds of this class, their salts and solvates thereof. These compounds are active in calcium and phosphate metabolism mediated disorders.
Alendronate sodium i.e (4-amin-1.-hydroxybutylidene) bisphosphonic acid is taught by the patent DE 3,016,289.
Patent number US 6,554,967 describes liquid formulation of alendronate monosodium trihydrate comprising of sodium propyl paraben, sodium butyl paraben, sodium citrate dihydrate, citric acid anhydrous, sodium hydroxide to adjust pH and water as a vehicle.
Another patent no. W09529679 relates to a process and a composition of bisphosphonic acid derivative. The composition is made by the wet granulation technique using water. The diluents comprise lactose and microcrystalline cellulose, which is wet granulated with bisphosphonic acid derivative. But in this, wet granulation of the drug with lactose may lead to problem of degradation of lactose containing dosage form with bisphosphonic acid derivatives with a primary or a secondary amine group.
Alendronic acid as monosodium salt trihydrate is an active ingredient of the pharmaceutical oral dosage formulation known as Fosamax®, indicated for the treatment and prevention of osteoporosis. Beside the active substance this formulation comprises of microcrystalline cellulose, anhydrous lactose, croscarmellose sodium and magnesium
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stearate as the excipients. Lactose, which is used in Fosamax , in its anhydrous form, is generally used as filler for solid dosage forms due to its excellent compressibility, high purity and stability.
However patent number WO 0185176 cites that this substance may generate formulation incompatibilities with the primary or secondary amine group containing compounds. The incompatibilities are caused by the reaction between the reducing aldehyde moiety of lactose and the amine group present in the active ingredient, known as the Maillard reaction. The resulting degradation products are inactive. The formation of the said products is evidenced by a brown coloring of the final drug dosage forms. The presence of water enhances the degradation. [(Reference: Handbook of Pharmaceutical Excipients, 2nd edition, 1994, pg. 257 (ISBN 091730 60 8)].
The bisphosphonic acid derivatives such as alendronic acid derivatives, etidronic acid derivatives, clodronic acid derivatives, pamidronic acid derivatives, ibandronaic acid derivative, tiludronic acid derivative, risedronic acid derivatives contain an amine group in their molecule. The problem of browning of lactose containing dosage form with alendronic acid and other bisphosphonic acid derivatives with a primary or a secondary amine group was disclosed in the International Patent Publication No. WO 94/12200. This patent proposes the method of avoiding the interaction of bisphosphonic acid derivatives comprising an amine group in the molecule with lactose by providing the dry composition of the active ingredient and lactose and the process of preparation thereof comprising the direct blending of the said dry mix without granulation or addition of water before compression.
Prior art US 5,358941, US 6,090,410 and US 5,681,590 granted to Merck & Co. claim a dry mix for bisphosphonic acids along with lactose in which lactose used is essentially anhydrous. The method as described for preparation of the formulation of these inventions is direct compression of said dry mix.
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Patent number US 5,849,726 and US 6,008,207 describe a formulation of anhydrous bisphosphonic acid derivative, viz, anhydrous alendronate monosodium along with anhydrous lactose and microcrystalline cellulose. The method of preparation as described therein is direct compression of a dry mix formulation comprising of the active ingredient lactose and other ingredients such as microcrystalline cellulose, magnesium stearate and crosscarmellose sodium.
Although patent WO 01/85176 appreciated these prior, arts for their ingenuity in attempting to stabilize the formulations, it still stated that the direct compression method of preparing these formulations did not however solve the instability problem of these pharmaceutical preparations during long storage, especially in warm and damp conditions. Therefore this patent describes a wet granulation method for preparation of a bisphosphonic acid derivative along with a carbohydrate alcohol such as D-mannitol. But the manner of preparing the dosage form dogs not bring the bisphosphonic acid derivative and mannitol directly in contact with water. The patent describes preparing a core of mannitol and cross-linked polyvinylpyrolidone and polyvinylpyrolidone by wet granulation and drying this core to obtain granules. This core is then combined with the active ingredient with the lubricant and other excipients. This blend is then compressed to form tablets. This patent claims that the quantity of mannitol is between 50 to 80%. But such a high quantity of mannitol may create problems with compressibility.
Therefore, it is clearly evident that the patent although claiming a wet granulation process of preparation of the said dosage form still anticipates degradation when the bisphosphonic acid derivative along with mannitol are intimately mixed with water or any such aqueous solvents.
Object
Therefore the object of the present invention is to provide an improved stable; formulation of bisphosphonic acid derivative along with atleast one carbohydrate alcohol, together with an aqueous binder aqueous binder.
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It is another object of the present invention to provide a simple method of manufacturing a stable formulation, which does not result in degradation of the bisphosphonic acid derivatives
It is yet another object of the present invention to provide an improved, stable formulation that is devoid of lactose thus avoiding degradation associated therewith.
It is yet another object of the present invention to provide a method of treating or preventing various skeletal diseases such as systemic bone diseases like osteoporosis, osteoarthritis, Paget's diseases, osteomalacia, multiple myeloma, and other forms of cancer, steroid therapy wherein the skeletal system is affected, age-related bone mass, local disorders, such as bone fractures and such other related disorders which comprises administering a therapeutically effective or prophylactic amount of a formulation according to the present invention.
Summary
Hence according to the present invention there is provided an improved, stable formulation comprising of bisphosphonic acid derivative or their salts, solvates, hydrates, enantiomers, prodrugs and racemic mixtures thereof along with at least one carbohydrate alcohol, together with an aqueous binder.
In another embodiment of the present invention there is provided a process of manufacture of an improved, stable formulation comprising of bisphosphonic acid derivative or their salts, solvates, hydrates, enantiomers, prodrugs and racemic mixtures thereof along with at least one carbohydrate alcohol using aqueous binder.
In yet another preferred embodiment of the present invention the is provided a method of treating or preventing various skeletal diseases such as systemic bone diseases like osteoporosis, osteoarthritis, Paget's diseases, osteomalacia, multiple myeloma, and other forms of cancer, steroid therapy wherein the skeletal system is affected, age-related bone mass, local disorders, such as bone fractures and such other related disorders which
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comprises administering a therapeutically effective or prophylactic amount of a formulation according to the present inention.
Description
Surprisingly, it has been found that a stable formulation comprising of bisphosphonic acid-derivatiye can be prepared by intimately mixing it with a carbohydrate alcohol using aqueous binder. The formulation so prepared by a simple technique is highly stable and does not result in degradation of the bisphosphonicacid derivative.
The present invention is therefore aimed at providing a stable formulation of a bisphosphonic acid derivative along with one or more carbohydrate alcohol together with an aqueous binder.
The advantage of wet granulating the bisphosphonic acid derivative along with the carbohydrate alcohol using an aqueous binder is that it helps achieve a better content uniformity of the drug. When the bisphosphonic acid derivative is added extragranular there might be a possibility of the drug not being uniformly mixed and thus the present invention overcomes this problem by incorporating the drug intragranularly.
The active ingredient may be selected from 4-amino-l- hydroxybutylidene)
bisphosphonic acid derivative, dichloromethylene bisphosphonic acid derivative, (1-
hydroxy-3-(methylpentylamino)propylidene)bisphosphonic acid) derivative, (1-
hydroxyethylidene) diphosphonic acid derivative, (3-amino-1-
hydroxypropylidene)bisphosphonic acid derivatives, [l-hydroxy-2-(3-pyridinyl) ethylidene]bisphosphonic acid derivative,[[(4-chlorophenyl)thio]methylene]bisphosphnic acid or , their salts, solvates, hydrates, prodrugs, enantiomers and racemic mixtures thereof. The bisphosphonic acid derivatives may be selected from alendronic acid, etidronic acid, clodronic acid, risedronic acid, pamidronic acid, ibandronaic acid, tiludronic acid and such other compounds of this class which are susceptible to degradation with lactose resulting in browning of the dosage form, and include their salts,
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solvates, derivatives, hydrates, enantiomers, prodrugs, racemic mixtures thereof. The salt of bisphosphonic acid is preferably sodium, disodium or trisodium salts. The bisphosphonic acid derivative may be used in the range of 0.5% to 40% with respect to the formulation.
The carbohydrate alcohols may be selected from Mannitol, Maltitol, Sorbitol, Lactitol, Erythritol, Xylitol such other compounds of this class, which do not contain a reducing aldehyde moiety in their chemical structure, their isomers and racemic mixtures thereof.
Along with the active ingredient, and carbohydrate alcohol, additional intragranular excipients such as diluents, disintegrants, binders may be employed. The diluents may comprise one or more of starches and cellulose derivatives like microcrystalline cellulose, cellulose powdered; calcium phosphate-dibasic, calcium sulfate, dextrates, dextrins, gums like alginates, dextrose excipients. The diluents may be added in a range of 15 to 90%. The preferred diluent is microcrystalline cellulose.
The disintegrants comprises one or more of low substituted hydroxypropyl cellulose, carboxymethyl cellulose, calcium carboxymethylcellulose, sodium carboxymethyl cellulose, sodium starch glycollate, crospovidone, croscarmellose sodium, starch, crystalline cellulose, hydroxypropyl starch, and partially pregelatinized starch. The disintegrant can be added in a range of 5 to 20%. The preferred disintegrant is Sodium starch glycollate.
The intragranular ingredients may be converted to granules by using suitable binders selected from natural and synthetic gums, celluloses such as hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose sodium, polyvinylpyrolidones, starches, gelatins and povidones and such other pharmaceutically acceptable substances with cohesive properties. The binder can be used in a range of 1 to 15%. The preferred binder is starch. The binder solution can be prepared using water.
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The granules may be further lubricated by employing lubricants/glidants selected from talc, magnesium stearate, stearic acid, hydrogenated vegetable oils, glyceryl behenate, polyethylene glycols and their derivatives sodium lauryl sulphate, sodium stearyl fumarate, and the like. The lubricants /glidants can be added in a quantity range of 0.5 to 5%. The preferred lubricant/glidants is magnesium stearate.
The present invention provides a simple method of manufacturing a stable formulation, which does not result in degradation of the bisphosphonic acid derivatives.
In another preferred embodiment of the present invention there is provided a process for manufacturing the present invention which process comprises mixing intimately the bisphosphonic acid derivative or their salts, solvates, hydrates, enantiomers, prodrugs and racemic mixtures thereof along with at least one carbohydrate alcohol using aqueous binder. The process is such that the bisphosphonic acid derivative comes in direct contact with the aqueous binder. The process comprises forming a dry blend of the said bisphosphonic acid derivative and at least one carbohydrate alcohol with other suitable intragranular excipients. It further comprises wet granulating the said dry blend with suitable aqueous binder to obtain the granules of the bisphosphonic acid derivative.
The granules so obtained can then be compressed to obtain the tablet else they can be encapsulated to obtain the capsules.
The said formulation as mentioned may be prepared as tablets in capsules, pellets, dry syrups, liquids and such other oral dosage form.
The formulation as provided by the present invention can be used in the treatment of various skeletal diseases such as systemic bone diseases like osteoporosis, osteoarthritis, Paget's disease, osteomalacia, multiple myleloma, and other forms of cancer, steroid,therapy and age-related loss of bone mass, local disorders such as bone fractures and such other related disorders.
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It is also provided by the present invention a formulation comprising of the active ingredients in therapeutic range so as to produce adequate therapeutic efficacy and subsequent relief in treatment of skeletal diseases such as systemic bone diseases like osteoporosis, osteoarthritis, Paget's disease, osteomalacia, multiple myleloma, and other forms of cancer, steroid, therapy and age-related loss of bone mass, local disorders such as bone fractures and such other related disorders.
The dosage forms as prepared contain the active ingredient in therapeutic range. The said formulation can be used to treat humans, particularly females who are post-menopausal, with an osteogenically effective amount of the bisphosphonic acid derivatives to inhibit bone resorption in need of such treatment. The term "bone resorption" as used herein, refers to treatment and prevention of bone loss, especially inhibiting the removal of existing bone either from the mineral phase and/or the organic matrix phase, through direct or indirect alteration of osteoclast formation or activity. Thus, the term "inhibitor of bone resorption" refers to agents that prevent bone loss by the direct or indirect alteration of osteoclast formation or activity and which may increase bone mass in the patient treatment populations. The term "osteogenically effective" as used herein, means that the amount, which affects the turnover of mature bone. As used herein, an osteogenically effective dose is also "pharmaceutically effective".
It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the scope and spirit of the invention. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be falling within the scope of the invention.
The following examples are for the purpose of illustration of the invention only and are not intended in any way to limit the scope of the invention.
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Example 1

SR. NO. INGREDIENTS QTY/TAB
(mg) QTY/TAB
(mg)
INTRAGRANULAR INGREDIENTS
1. Alendronate Sodium Trihydrate equivalent to alendronic acid 35 70
2. Microcrystalline cellulose 57.5 115.0
3. Mannitol 58.32 116.63
4. Sodium Starch Glycollate 7.5 15.0
BINDER SOLUTION
5. Starch 1.5 3.0
6. Purified Water q.s. q.s.
EXTRAGRANULAR INGREDIENTS
7. Magnesium Stearate 2.00 4.00
8. Sodium Starch Glycollate 2.5 5.00
TOTAL 175.00 350.00
PROCESS:
Pre-sifted Alendronate sodium trihydrate, sodium starch glycollate, mannitol, microcrystalline cellulose were dry-mixed in the Fluidized Bed Processor for 5 mins. Binder solution was prepared using starch and purified water. This binder solution was hen sprayed over the drymix at a specified rate and temperature to obtain granules. The granules were then spray dried and sifted. The granules were then blended in a suitable blender along with sodium starch glycollate and pre-sifted magnesium stearate. The granules were then compressed to form tablets.
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Example 2:

SR. NO. INGREDIENTS QTY/TAB
(mg)
INTRAGRANULAR INGREDIENTS
1. Etidronate disodium equivalent to etidronic acid 200
2. Microcrystalline cellulose 158.20
3. Mannitol 156.64
4. Sodium Starch Glycollate 20.14
BINDER SOLUTION
5. Starch 4.0
6. Purified Water q.s.
EXTRAGRANULAR INGREDIENTS
7. Magnesium Stearate 5.52
8. Sodium Starch Glycollate 5.5
TOTAL 550.00
Process:
Pre-sifted Etidronate disodium, sodium starch glycollate, mannitol, microcrystalline cellulose were dry-mixed in the Fluidized Bed Equipment for 5 mins. Binder solution was prepared using starch and purified water. This binder solution was then sprayed over the drymix at a specified rate and temperature to obtain granules. The granules were then spray dried and sifted followed by mixing them in a suitable blender along with sodium starch glycollate and pre-sifted magnesium stearate. The granules were then filled in capsules.
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Example 3:

SR. NO. INGREDIENTS QTY/TAB
(mg)
INTRAGRANULAR INGREDIENTS
1. Risedronate sodium monohydrate equivalent to Risedronic acid. 30
2. Microcrystalline cellulose 45.3
3. Mannitol 55.6
4. Sodium Starch Glycollate 4.9
BINDER SOLUTION
5. Starch 1
6. Purified Water q.s.
EXTRAGRANULAR INGREDIENTS
7. Magnesium Stearate 1.3
8. Sodium Starch Glycollate 1.6
TOTAL 140.00
Process:
Pre-sifted Risedronate sodium monohydrate, sodium starch glycollate, mannitol, microcrystalline cellulose were dry-mixed in the Fluidized Bed Equipment for 5 mins. Binder solution was prepared using starch and purified water. This binder solution was then sprayed over the dry mix at a specified rate and temperature to obtain granules. The granules were then spray dried and sifted followed by mixing them in a suitable blender along with sodium starch glycollate and pre-sifted magnesium stearate. The granules were then filled in capsules.
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claim
1. A stabilized oral dosage pharmaceutical composition of bisphosphonic acid derivative comprising at least one carbohydrate alcohol, which do not contain a reducing aldehyde moiety, together with an aqueous binder; wherein said composition is devoid of lactose.
2. The oral dosage pharmaceutical composition as claimed in claims 1 wherein said bisphosphonic acid derivative is selected from alendronic acid, clodronic acid, etidronic acid, ibandronaic acid, tiludronic acid pamidronic acid, risedronic acid, their salts, salts, solvates, hydrates, prodrugs, enantiomers and racemic mixtures thereof and such other compounds of this class.
3. The oral dosage pharmaceutical composition as claimed in claim 2, wherein said salt of bisphosphonic acid is preferably sodium, disodium or trisodium salts.
4. The oral dosage pharmaceutical composition as claimed in claims 1 to 3, wherein, said bisphosphonate derivative is alendronate sodium trihydrate.
5. The oral dosage pharmaceutical composition as claimed in claims 1 to 3, wherein, said bisphosphonate derivative is etidronate disodium.
6. The oral dosage pharmaceutical composition as claimed in claims 1 to 3, wherein, said bisphosphonate derivative is risedronate sodium monohydrate.
7. The oral dosage pharmaceutical composition as claimed in claim 1 wherein said carbohydrate alcohol is selected from mannitol, maltitol, sorbitol, lactitol, erythritol and xylitol.
8. The oral dosage pharmaceutical composition as claimed in claim land 7, wherein said carbohydrate alcohol is mannitol.
9. The oral dosage pharmaceutical composition as claimed in claim 8, wherein said mannitol is in the range of 15 to 90%.
10. The oral dosage pharmaceutical composition as claimed in claim 9, wherein said mannitol is in the range of _15.to 50%.
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11. The oral dosage pharmaceutical composition as claimed in claim 10, wherein said mannitol is in the range of 15 to 40%.
12. The oral dosage pharmaceutical composition as claimed in claims 1 to 11, wherein said pharmaceutical composition is a tablet.
13. The oral dosage pharmaceutical composition as claimed in claim 1, wherein said disintegrants comprise one or more of low substituted hydroxypropyl cellulose, carboxymethyl cellulose, calcium carboxymethylcellulose, sodium carboxymethyl cellulose, sodium starch glycollate, crospovidone, croscarmellose sodium, starch, crystalline cellulose, hydroxypropyl starch, and partially pregelatinized starch.
14. The oral dosage pharmaceutical composition as claimed in claim 13, wherein said pharmaceutical composition comprises 5 to 20% of disintegrant.
15. The oral dosage pharmaceutical composition as claimed in claims 13 and 14, wherein said disintegrant is sodium starch glycollate.
16. The oral dosage pharmaceutical composition as claimed in claim 1, wherein said lubricants/glidants comprise one or more of talc, magnesium stearate, stearic acid, hydrogenated vegetable oils, glyceryl behenate, polyethylene glycols and their derivatives, sodium lauryl sulphate and sodium stearyl fumarate.
17. The oral dosage pharmaceutical composition as claimed in claims 1 and 16, wherein said pharmaceutical composition comprises 0.5 to 5% of said lubricants/glidants.
18. The oral dosage pharmaceutical composition as claimed in claims 1,16 and 17, wherein said lubricant/glidant is magnesium stearate.
19. The oral dosage pharmaceutical composition as claimed in claim 1, wherein said binder comprises one or more of natural and synthetic gums, celluloses such as hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose sodium, polyvinylpyrolidones, starches, gelatins and povidones.
Vt

20. The oral dosage pharmaceutical composition as claimed in claims 1 and 19, wherein said pharmaceutical composition comprises 1 to 15% of binder.
21. The oral dosage pharmaceutical composition as claimed in claims 19 and 20, wherein said binder is starch.
22. The oral dosage pharmaceutical composition as claimed in claim 1, wherein said diluents comprises one or more of starches and cellulose derivatives like microcrystalline cellulose, cellulose powdered, calcium phosphate-dibasic, calcium sulfate, dextrates, dextrins and dextrose.
23. The oral dosage pharmaceutical composition as claimed in claims 1 and 22, wherein said pharmaceutical composition comprises 15 to 90% of the diluent.
24. The oral dosage pharmaceutical composition as claimed in claims 22 and 23, wherein said diluent is microcrystalline cellulose.
25. A process for the manufacture of a stabilized pharmaceutical composition comprising the steps of:
Dry mixing of bisphosphonic acid derivative or their salts, solvates, hydrates, enantiomers, prodrugs and racemic mixtures thereof and at least one carbohydrate alcohol along with other suitable intragranular excipients; and wet granulating the dry mix using suitable aqueous binder solution to obtain the granules.
26. The process as claimed in claim 25, wherein the wet granulation of the bisphosphonic acid derivative and at least one carbohydrate alcohol, such that the bisphosphonic acid derivative comes in direct contact with the aqueous binder.
27. The process as claimed in claims 25 and 26, wherein said process further comprises compressing the granules obtained according to claim 25 to form a tablet.
28. The oral dosage pharmaceutical composition as claimed in claim 1 to 24, wherein said composition is a capsule.
IS

29. The oral dosage pharmaceutical composition as claimed in claim 28, wherein said capsule comprises encapsulating the granules obtained according to claims 25 and 26.
30. The oral dosage pharmaceutical composition as claimed in claims 1 to 24, wherein said composition is formulated as tablets in capsules, pellets, dry syrups, liquids and such other oral dosage forms.
Dated this the 28 th day of September 2004-





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Dr. Gopakumar G. Nair
Agent for the Applicant

Documents:

1023-mum-2003-abstract(complete)-(28-9-2004).pdf

1023-mum-2003-cancelled pages(18-04-2006).pdf

1023-mum-2003-cancelled pages(27-3-2006).pdf

1023-mum-2003-claims(amended)-(18-4-2006).pdf

1023-mum-2003-claims(complete)-(28-9-2004).pdf

1023-mum-2003-claims(granted)-(18-04-2006).doc

1023-mum-2003-claims(granted)-(18-04-2006).pdf

1023-mum-2003-claims(granted)-(29-6-2007).pdf

1023-mum-2003-claims.doc

1023-mum-2003-claims.pdf

1023-mum-2003-correspondence(18-04-2006).pdf

1023-mum-2003-correspondence(18-4-2006).pdf

1023-mum-2003-correspondence(ipo)-(24-04-2006).pdf

1023-mum-2003-correspondence(ipo)-(30-7-2007).pdf

1023-mum-2003-correspondence(ipo).pdf

1023-mum-2003-correspondence.pdf

1023-mum-2003-description(complete)-(28-9-2004).pdf

1023-mum-2003-description(granted)-(29-6-2007).pdf

1023-mum-2003-description(granted).doc

1023-mum-2003-description(granted).pdf

1023-mum-2003-description(provisional)-(29-9-2003).pdf

1023-mum-2003-form 1(18-04-2006).pdf

1023-mum-2003-form 1(18-4-2006).pdf

1023-mum-2003-form 1(27-3-2006).pdf

1023-mum-2003-form 1(29-09-2003).pdf

1023-mum-2003-form 1.pdf

1023-mum-2003-form 18(26-08-2005).pdf

1023-mum-2003-form 18.pdf

1023-mum-2003-form 2(complete)-(28-9-2004).pdf

1023-mum-2003-form 2(garanted).doc

1023-mum-2003-form 2(granted)-(18-04-2006).doc

1023-mum-2003-form 2(granted)-(18-04-2006).pdf

1023-mum-2003-form 2(granted)-(29-6-2007).pdf

1023-mum-2003-form 2(granted).pdf

1023-mum-2003-form 2(provisional)-(29-9-2003).pdf

1023-mum-2003-form 2(provisional).pdf

1023-mum-2003-form 2(title page)-(complete)-(28-9-2004).pdf

1023-mum-2003-form 2(title page)-(granted)-(29-6-2007).pdf

1023-mum-2003-form 2(title page)-(provisional)-(29-9-2003).pdf

1023-mum-2003-form 2(title page).pdf

1023-mum-2003-form 26.pdf

1023-mum-2003-form 3(27-03-2006).pdf

1023-mum-2003-form 3(27-3-2006).pdf

1023-mum-2003-form 3(29-9-2003).pdf

1023-mum-2003-form 3.pdf

1023-mum-2003-form 5(28-09-2004).pdf

1023-mum-2003-form 5.pdf

1023-mum-2003-form-pct-isa-210(18-10-2005).pdf

1023-mum-2003-form-pct-isa-210.pdf

1023-mum-2003-form-pct-isa-237.pdf

1023-mum-2003-other document(27-3-2006).pdf

1023-mum-2003-specification(amended)-(27-3-2006).pdf


Patent Number 207880
Indian Patent Application Number 1023/MUM/2003
PG Journal Number 31/2008
Publication Date 01-Aug-2008
Grant Date 29-Jun-2007
Date of Filing 29-Sep-2003
Name of Patentee M/S. CIPLA LIMITED
Applicant Address 289, BELLASIS ROAD, MUMBAI CENTRAL, MUMBAI - 400008
Inventors:
# Inventor's Name Inventor's Address
1 LULLA, AMAR 131, MAKER TOWER-L, 13TH FLOOR, CUFFE PARADE, COLABA, MUMBAI 400 005, MAHARASHTRA
2 Malhotra, Gcena 4, Anderson House, Opp. Mazgaon Post Office, Mazgaon, Mumbai
PCT International Classification Number A61K 31/66
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA