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WO2009087581A1 - Procédé perfectionné pour la préparation de polysulfate de pentosane ou de ses sels - Google Patents

Procédé perfectionné pour la préparation de polysulfate de pentosane ou de ses sels Download PDF

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Publication number
WO2009087581A1
WO2009087581A1 PCT/IB2009/050001 IB2009050001W WO2009087581A1 WO 2009087581 A1 WO2009087581 A1 WO 2009087581A1 IB 2009050001 W IB2009050001 W IB 2009050001W WO 2009087581 A1 WO2009087581 A1 WO 2009087581A1
Authority
WO
WIPO (PCT)
Prior art keywords
salt
picoline
xylan
pentosan polysulfate
sodium
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IB2009/050001
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English (en)
Other versions
WO2009087581A4 (fr
Inventor
Keshav Deo
Ashok Prasad
Hitesh Patel
Dharmesh Dhameliya
Bharat Patel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alembic Ltd
Original Assignee
Alembic Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Alembic Ltd filed Critical Alembic Ltd
Publication of WO2009087581A1 publication Critical patent/WO2009087581A1/fr
Publication of WO2009087581A4 publication Critical patent/WO2009087581A4/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0057—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Xylans, i.e. xylosaccharide, e.g. arabinoxylan, arabinofuronan, pentosans; (beta-1,3)(beta-1,4)-D-Xylans, e.g. rhodymenans; Hemicellulose; Derivatives thereof

Definitions

  • the present invention relates to an improved process for the preparation of Pentosan polysulfate of formula (I)
  • R represents -SO 3 Y
  • Y is at least one member selected from the group consisting of H and a pharmaceutically acceptable cation such as sodium and potassium.
  • Pentosan polysulfate sodium is chemically known as Beta-D-Xylan, (1-4), 2, 3-bis (hydrogen sulphate) sodium salt having molecular weight range of 4000 to 6000 Dalton.
  • the structural formula of Pentosan polysulfate sodium represents as below:
  • Pentosan polysulfate sodium [37319-17-8] is a semi- synthetically produced heparin- like macromolecular carbohydrate derivative which chemically and structurally resembles glycosaminoglycans. It is a white odorless powder, slightly hygroscopic and soluble in water.
  • Pentosan polysulfate sodium is a mixture of linear polymers of Beta-1 -> 4-linked xylose, usually sulfated at the 2- and 3-positions and occasionally substituted at the 2-position with 4-O-methyl-alpha-D-glucuronic acid 2, 3-O-suflate.
  • Pentosan polysulfate is a semi-synthetic compound whose polysaccharide backbone, xylan is extracted from the bark of the beech tree or other plant sources and then treated with sulfating agents such as chlorosulfonic acid or sulfuryl chloride and acid. After sulfation, Pentosan polysulfate is usually treated with sodium hydroxide to yield the sodium salt.
  • Pentosan polysulfate was disclosed in US patent no. 2689848. The process wherein
  • Xylan was treated with chlorosulfonic acid in the presence of pyridine to obtain sulfuric acid ester salt of xylan followed by oxidative depolymerisation in acidic or neutral aqueous medium to obtain depolymerised product which was dialyzed and followed the fractionation process to obtain desired product.
  • the isolation of sulfuric acid ester salt of xylan provides sticky material.
  • this process did not provide end product with desired molecular weight.
  • US patent no. 2689848 disclosed the process for the production of salts of sulfuric acid ester of Xylan, the steps which comprised oxidizing the aqueous solution of the salt of a sulfuric acid ester of highly polymeric xylan in an aqueous solution of H 2 O 2 and H 2 SO 4 to depolymerize such highly polymeric xylan ester partially, dialyzing the depolymerized product and fractionating an aqueous solution of the dialyzate with an organic water miscible solvent to obtain a fraction having a Z ⁇ value between 0.0030 and 0.015 and sulfur content of 13.5 to 17%.
  • the present invention relates to an improved process for preparation of Pentosan polysulfate of formula (I) or salt thereof, comprising a step of treating xylan with chlorosulfonic acid in the presence of picoline.
  • Another object of the present invention is to provide an improved process for the preparation of Pentosan polysulfate of formula (I) or salt thereof.
  • Another object of the present invention is to provide the process for the preparation of Pentosan polysulfate of formula (I) or its salt which is operationally simple, easy to handle and applicable at an industrial scale.
  • Yet another object of the present invention is to provide an improved process for preparation of Pentosan polysulfate of formula (I) or salt thereof, comprising steps of: [35] i) treating xylan with chlorosulfonic acid in the presence of picoline followed by addition of alkali in the presence of alcoholic solvent to obtain salt of sulfuric acid ester of xylan [36] ii) oxidizing the salt of sulfuric acid ester of xylan with the mixture of H 2 SO 4 and
  • a further object of the present invention is to provide an improved process for preparation of Pentosan polysulfate of formula (I) or salt thereof, comprising a step of treating xylan with chlorosulfonic acid in the presence of picoline.
  • present invention provides an improved process for the preparation of Pentosan polysulfate of formula (I)
  • R represents -SO 3 Y
  • Y is at least one member selected from the group consisting of H and a pharmaceutically acceptable cation such as sodium and potassium.
  • present invention provides an improved process for the preparation of Pentosan polysulfate of formula (I) or salt thereof, which is operationally simple, easy to handle and applicable at an industrial scale.
  • Yet another aspect of the present invention is to provide an improved process for preparation of Pentosan polysulfate of formula (I) or salt thereof, comprising a step of treating xylan with chlorosulfonic acid in the presence of picoline.
  • the picoline in step (i) is selected from alpha-picoline, Beta-picoline, Gamma- picoline and the like or mixtures thereof.
  • the suitable alkali in step (i) is selected from alkali metal salt of carbonate, bicarbonate, hydroxide or mixtures thereof.
  • the preferable is sodium hydroxide, sodium carbonate, potassium carbonate, potassium hydroxide and the like thereof.
  • the most preferable is sodium hydroxide
  • the suitable alcoholic solvent in step (i) is selected from methanol, ethanol, propanol, isopropanaol, butanol or mixtures thereof. The most preferable is methanol.
  • the suitable alcohol for crystallization is selected from methanol, ethanol, propanol, isopropanaol, butanol or mixtures thereof.
  • the most preferable is methanol.
  • chlorosulfonic acid is added slowly to Beta-picoline at below 35-45 0 C.
  • the resulting salt is heated to 60-65 0 C before addition of xylan and is raised the temperature to 75-8O 0 C for 3-4 hrs.
  • reaction mixture is cooled to room temperature and water is added and then allows standing for 12 hrs after adding chlorine dioxide solution. Subsequently this solution is allowed to flow into a mixture of methanolic sodium hydroxide solution.
  • the reaction mixture is stirred for 30 min at room temperature.
  • the solution is then adjusted to pH 6.5 to 7.0 by addition of glacial acetic acid.
  • the resulting salt is isolated by filtration followed by washing with methanol and finally drying at 45-5O 0 C to obtain Sodium salt of sulfuric acid ester of xylan.
  • reaction mixture 90-100 0 C, then addition of preheated mixture of 5N H 2 SO 4 and 30% hydrogen peroxide.
  • the reaction mixture is maintained at 90-100 0 C.
  • the reaction mixture is cooled to 25-3O 0 C followed by adjustment of pH 7.5-7.3 with 5N sodium hydroxide solution.
  • the reaction mixture is subjected to the NF membrane of cut off molecular weight of 4000-6000 Dalton, filtration.
  • the NF Membrane system is monitored the rejection of lower molecular weight material with HPLC.
  • the concentrate is subjected to water recovery at 50-60 0 C under reduced pressure. Finally residue is crystallized with methanol to get the pure Pentosan polysulfate sodium.
  • the material is filtered and dried to get pure Pentosan polysulfate sodium.
  • the concentrate is transferred in a single neck round bottom flask and fitted to Lyophilizer (BT4KZL-105) and starts the operation of lyophilyzation. It takes about 24 hr to complete the lyophilyzation and provides Pentosan polysulfate sodium.
  • the filtration step as discussed hereinabove is carried out by using NF Membrane system 'PERMA' Pilot Membrane System manufactured by PERMIONIC Membranes Pvt. Ltd., 3/29, 4/19, B.I.D.C, Gorwa Estate, Vadodara- 390016, India.
  • the meaning of the term 'NF membrane system' is nano-filtration accompanied by membrane which is capable to pass the undesired product having molecular weight of at least 4000 Dalton.
  • the present invention provides high yield of salt of sulfuric acid ester of xylan which is free flow in nature.
  • Beta-picoline (lit) was added in chlorosulfonic acid (200 ml) slowly at below
  • reaction mixture was decolorized by 200ml chlorine dioxide with water (500 ml). The decolorized solution was filtered through celite bed and filtrate was neutralized with aqueous methanolic sodium hydroxide solution and crystallized with methanol to get sodium salt of sulfuric acid ester of Xylan (250 gm).
  • the concentrate was subjected to water recovery at 50-60 0 C under reduced pressure up to 300ml. Finally the concentrated solution was subjected to spray drying to get the Pentosan polysulfate sodium having Molecular weight 4000-6000 of Dalton. The yield of pure Pentosan polysulfate sodium was 200 gm.

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Materials Engineering (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention vise à proposer un procédé perfectionné pour la préparation de polysulfate de pentosane de formule (I) ou un sel de celui-ci, comprenant une étape de traitement de xylane par de l'acide chlorosulfonique en présence de picoline.
PCT/IB2009/050001 2008-01-04 2009-01-01 Procédé perfectionné pour la préparation de polysulfate de pentosane ou de ses sels Ceased WO2009087581A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN34MU2008 2008-01-04
IN34/MUM/2008 2008-01-04

Publications (2)

Publication Number Publication Date
WO2009087581A1 true WO2009087581A1 (fr) 2009-07-16
WO2009087581A4 WO2009087581A4 (fr) 2009-10-08

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WO (1) WO2009087581A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012114349A1 (fr) 2011-02-23 2012-08-30 Cadila Healthcare Limited Procédé amélioré pour la préparation de pentosane polysulfate sodium
CN102766225A (zh) * 2011-05-06 2012-11-07 上海医药工业研究院 一种戊聚糖聚硫酸钠的制备方法以及一种寡聚木糖
WO2013116366A1 (fr) 2012-01-30 2013-08-08 Baxter International Inc. Polysaccharides sulfatés ou sulfonés non anticoagulants
ITMI20130112A1 (it) * 2013-01-24 2014-07-25 Chemi Spa Metodo di qualificazione di preparazioni di pentosan polifosfato, sue materie prime e processi di produzione
WO2018159580A1 (fr) * 2017-02-28 2018-09-07 王子ホールディングス株式会社 Polysulfate de pentosane, composition pharmaceutique et anticoagulant
WO2020039480A1 (fr) 2018-08-20 2020-02-27 株式会社レクメド Nouvelle préparation de pentosane polysulfate sodique
US11278485B2 (en) 2017-05-31 2022-03-22 Oji Holdings Corporation Moisturizing topical preparation
US11286272B2 (en) 2016-08-31 2022-03-29 Oji Holdings Corporation Production method for acidic xylooligosaccharide, and acidic xylooligosaccharide
US11312790B2 (en) 2016-08-31 2022-04-26 Oji Holdings Corporation Production method for pentosan polysulfate
US11344570B2 (en) 2017-12-20 2022-05-31 Oji Holdings Corporation Pentosan polysulfate and medicine containing pentosan polysulfate
US11390693B2 (en) 2017-09-12 2022-07-19 Oji Holdings Corporation Pentosan polysulfate and method for producing pentosan polysulfate

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2689848A (en) * 1951-02-06 1954-09-21 Wander Ag Dr A Salts of sulfuric acid esters of xylan
US4713373A (en) * 1984-11-07 1987-12-15 Sanofi S.A. Xylan sulfates of low molecular weight, process for their preparation and medicaments containing them
WO1988000211A1 (fr) * 1986-07-07 1988-01-14 Pharmacia Ab Procede de preparation de polysaccharides sulfates par traitement du polysaccharide avec un agent reducteur avant sulfatation
WO2008107906A1 (fr) * 2007-03-06 2008-09-12 Alembic Limited Processus de préparation de polysulfate de pentosane ou de ses sels

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2689848A (en) * 1951-02-06 1954-09-21 Wander Ag Dr A Salts of sulfuric acid esters of xylan
US4713373A (en) * 1984-11-07 1987-12-15 Sanofi S.A. Xylan sulfates of low molecular weight, process for their preparation and medicaments containing them
WO1988000211A1 (fr) * 1986-07-07 1988-01-14 Pharmacia Ab Procede de preparation de polysaccharides sulfates par traitement du polysaccharide avec un agent reducteur avant sulfatation
WO2008107906A1 (fr) * 2007-03-06 2008-09-12 Alembic Limited Processus de préparation de polysulfate de pentosane ou de ses sels

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012114349A1 (fr) 2011-02-23 2012-08-30 Cadila Healthcare Limited Procédé amélioré pour la préparation de pentosane polysulfate sodium
CN102766225A (zh) * 2011-05-06 2012-11-07 上海医药工业研究院 一种戊聚糖聚硫酸钠的制备方法以及一种寡聚木糖
WO2013116366A1 (fr) 2012-01-30 2013-08-08 Baxter International Inc. Polysaccharides sulfatés ou sulfonés non anticoagulants
EP3415153A1 (fr) 2012-01-30 2018-12-19 Baxalta GmbH Polysaccharides sulfatés ou sulfonés non anticoagulants
US11242412B2 (en) 2013-01-24 2022-02-08 Chemi S.P.A. Method for the qualification of preparations of pentosan polysulfate, raw materials and production processes thereof
ITMI20130112A1 (it) * 2013-01-24 2014-07-25 Chemi Spa Metodo di qualificazione di preparazioni di pentosan polifosfato, sue materie prime e processi di produzione
WO2014114723A1 (fr) * 2013-01-24 2014-07-31 Chemi S.P.A. Procédé pour la qualification de préparations de polysulfate de pentosane, matières premières et de procédés de production associés
US10407515B2 (en) 2013-01-24 2019-09-10 Chemi S.P.A. Method for the qualification of preparations of pentosan polysulfate, raw materials and production processes thereof
US11286272B2 (en) 2016-08-31 2022-03-29 Oji Holdings Corporation Production method for acidic xylooligosaccharide, and acidic xylooligosaccharide
US11312790B2 (en) 2016-08-31 2022-04-26 Oji Holdings Corporation Production method for pentosan polysulfate
US11274165B2 (en) 2017-02-28 2022-03-15 Oji Holdings Corporation Pentosan polysulfate, pharmaceutical composition, and anticoagulant
WO2018159580A1 (fr) * 2017-02-28 2018-09-07 王子ホールディングス株式会社 Polysulfate de pentosane, composition pharmaceutique et anticoagulant
US11278485B2 (en) 2017-05-31 2022-03-22 Oji Holdings Corporation Moisturizing topical preparation
US11390693B2 (en) 2017-09-12 2022-07-19 Oji Holdings Corporation Pentosan polysulfate and method for producing pentosan polysulfate
US11344570B2 (en) 2017-12-20 2022-05-31 Oji Holdings Corporation Pentosan polysulfate and medicine containing pentosan polysulfate
WO2020039480A1 (fr) 2018-08-20 2020-02-27 株式会社レクメド Nouvelle préparation de pentosane polysulfate sodique

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