Title of Invention

A PROCESS FOR PREPARING DIOSMIN

Abstract

An improved process for preparing pure diosmin, comprising the following steps, a) dissolving hesperidine in a solvent followed by adding of sodium hydroxide under constant stirring, b) adding iodine portion wise within one hour to the mixture obtained at step (a), kept mixture constant for a period of 6-8 hrs at 80-90C c) distillation of solvent followed by adding sodium thiosulphate, and water allowed to filter to get crude diosmin followed by stirring with conc.Hcl allow to filter d) conversion of crude diosmin into sodium salt by dissolution in NaoH, water and carbon-treated with followed by filteration again treated with sulphuric acid until to achieve Ph-2, e) filtering and washing the product obtained at step (d).

Full Text

FORM 2 THE PATENTS ACT, 1970 (39 of 1970) COMPLETE SPECIFICATION (See section 10; rule 13) Title :- A process for preparing Diosmin, ELDER PHARMACEUTICALS LTD. Elder House, Plot No. C/9, Dalia Indl. Estate, Off. NewLinkRoad,Andheri (W), Mumbai - 400 058, India. 3 0 NOV .004 Title : - A process for preparing Diosmin, Filed of the Invention : - The present invention relates to a process for the preparing Diosmin , in the field of pharmaceuticals/ drug, more particularly 7-[[6-0-(6-Deoxy-a-L-mannopyransoyl)-[3-D-glucopyranosyl]oxy]-5- hydroxy-2-(3-hydroxy-4-methoxyphenyl)-4H- l-benzopyran-4-one , and 3",5,7-trihydroxy-4"methoxyflavone-7-rutinoside, 5-hydroxy-4"methoxy-2- (3-hydroxy-4-methoxy-4-methoxyphenyl)-7-(06-a-L-rhamnopyransyl-b-D- glucopyran0syloxy)chrome-4-one, and 5-hydroxy-2-(3-hydroxy-4- methoxyphenyl)-7-P-rutinosyloxy-4H-chromen-4-one„ and or diosmethin-7-B-rutinoside . Back Ground and Prior art ;- The present invention relates to a new and improved process for the preparing pure diosmin , having molecular formula ( C.sub.28.sub.320?sub.l5). Suitable for use as therapeutic agent .This also can be used as a tonic agent for veins or a liver protective agent is well known. The diosmin manufactured in accordance with the process described in the prior art publication is genrally obtained with small yield and purity but an instant process describes to obtained pure diosmin with several purification techniques as and using less solvents and reagent, where as in the prior art reported utilized more than one solvents and reagent, which would leads to more of manufacturing and less purity . As per the prior art the use of morpholin for the removal of iodine has been totally eliminated in the present invention by simple and efficient techniques The solvent used in the present in the present invention is pyridine as compared with Dimethyl formamide , Dimethyl acetamide , morpholine & DMSO. Objects;- Primary object of the present invention isuse of morpholine for the removal of iodine which would drastically reduces the cost of manufacturing at industrial level. Further object of the present invention is , while using a single solvent and reagents , and with less purification steps will reduces the time and manufacturing cost, also give pure product within less time and cost. Description ;- The present invention relates to an improved process for the preparation of pure diosmin comprising the following steps , Reaction Scheme 2 above stirred mixture in 1 hour. The mixture is maintained at 80-90°C for 6-8 hrs. after which the pyridine is distilled off under vacuum and aqueous sodium thiosulpate 5 gm , 0.02 mole are added. 1.0 Ltr water is added and the contained are filtered at pump.The crude Diosmin is than slurried with Conc. HCI 350 ml and filtered once again to yield 91 gm. This crude Diosmin is converted in to the sodium salt by dissolution in sodium hydroxide 50 gm, 1.25 mole in 1.0 Ltr water, carbon-treated and the filtrated is treated with 98% Sulphuric acid to achieve a pH 2.The product is filtered and washed with hot water followed by methanol and sucked dry. On drying the pure Diosmin weigh 85 gms with an HPLC purity of above 98.6%. Illustrative Examples Example : 1 4 The reaction was performed as per the representative example except for reduced quantity of Pyridine i.e. 400 ml. The purity of the final product fails to achieve the desired pharmacoepial standards. Example : 2 The reaction was performed as per the representative example except for the substitution of pyridine by dimethyl formamide 500 ml. The yield in this case too, was very low. Example : 3 The reaction was performed as per the representative example except for the substitution of pyridine by N,N-dimethyl acetamide 500 ml. The conversion of 2.61% was noted with the large formation of undesirable impurities. Example : 4 The reaction was performed as per the representative example; except for the substitution of pyridine by morpholine 500 ml. Diosmin was found to an extent of 52% having a melting point of 273-276°C. Example : 5 The reaction was performed as per the representative example, except for the substitution of pyridine and NaOH by DMSO and KOH respectively. There was 70% conversion of Hesperidin into Diosmin. The product melted at 273-276°C. Example : 6 The reaction was performed as per the representative example except for the reduction of Iodine (41 gm, 0.161 mole). The conversion was incomplete due to the reduced iodine content. We claim, 5 1. An Improved process for preparing pure diosmin , comprising the following steps, a) dissolving hesperidine in a solvent followed by adding of sodium hydroxide under constant stirring , b) adding iodine portion wise within one hour to the mixture obtained at step (a) , kept mixture constant for a period of 6-8 hrsat 80-90C c) distillation of solvent followed by adding sodium thiosulphate . and water allowed to filter to get crude diosmin followed by stirring with conc.Hcl allow to filter d) conversion of crude diosmin into sodium salt by dissolution in NaoH, water and carbon - treated i followed by Alteration agin treated with sulphuric acid until to achieve Ph-2, e) filtering and washing the product obtained at step (d) 2. A process as claimed in claim 1, wherein solvent used is pyridine 3. A process as claimed in claim 1, wherein washing the product is done using methanol. 4. An Improved process for preparing pure diosmin such as here in described with reference to forgoing examples , Dated this 04 th day of Nov. 2004 6

Documents:

1184-mum-2004- claims.doc

1184-mum-2004-claims(granted)-(30-11-2004).doc

1184-mum-2004-claims.pdf

1184-mum-2004-correspondence(28-12-2004).pdf

1184-mum-2004-correspondence(ipo)-(13-12-2004).pdf

1184-mum-2004-correspondence(ipo).pdf

1184-mum-2004-correspondence.pdf

1184-mum-2004-description(granted).doc

1184-mum-2004-description(granted).pdf

1184-mum-2004-drawing(30-11-2004).pdf

1184-mum-2004-form 1(04-11-2004).pdf

1184-mum-2004-form 1(30-11-2004).pdf

1184-mum-2004-form 1.pdf

1184-mum-2004-form 19(04-11-2004).pdf

1184-mum-2004-form 19.pdf

1184-mum-2004-form 2(granted)-(30-11-2004).doc

1184-mum-2004-form 2(granted)-(30-11-2004).pdf

1184-mum-2004-form 2(granted).pdf

1184-mum-2004-form 2(provisional specification).pdf

1184-mum-2004-form 2(title page).pdf

1184-mum-2004-form 3(30-11-2004).pdf

1184-mum-2004-form 3.pdf

1184-mum-2004-form 5(30-11-2004).pdf

1184-mum-2004-form 5.pdf

1184-mum-2004-form-2(garanted).doc