[go: up one dir, main page]

WO2012101544A1 - Procédé de préparation amélioré de polysulfate de pentosane ou de sels de celui-ci - Google Patents

Procédé de préparation amélioré de polysulfate de pentosane ou de sels de celui-ci Download PDF

Info

Publication number
WO2012101544A1
WO2012101544A1 PCT/IB2012/050213 IB2012050213W WO2012101544A1 WO 2012101544 A1 WO2012101544 A1 WO 2012101544A1 IB 2012050213 W IB2012050213 W IB 2012050213W WO 2012101544 A1 WO2012101544 A1 WO 2012101544A1
Authority
WO
WIPO (PCT)
Prior art keywords
pentosan polysulfate
salt
formula
xylan
crude
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/IB2012/050213
Other languages
English (en)
Inventor
Jayaraman Venkat Raman
Bijukumar Gopinathan Pillai
Sundara Kalyana BALAJI
Hitesh Patel
Dharmesh Dhameliya
Govind JINJALA
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 Pharmaceuticals Ltd
Original Assignee
Alembic Pharmaceuticals 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 Pharmaceuticals Ltd filed Critical Alembic Pharmaceuticals Ltd
Publication of WO2012101544A1 publication Critical patent/WO2012101544A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

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
    • 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
    • C08B37/0003—General processes for their isolation or fractionation, e.g. purification or extraction from biomass

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, potassium, and magnesium which provides in particular to a narrow distribution low molecular weight, highly sulfated Pentosan polysulfate (in this instance a Xylan).
  • Pentosan polysulfate sodium represents as below:
  • Pentosan polysulfate sodium salt is being sold by Ortho McNeil under the tradename Elmiron ® in the form of capsules which is used for the treatment of bladder infection, interstitial cystitis and tumors.
  • Pentosan polysulfate sodium is chemically known as ⁇ -D-Xylan, (1-4), 2, 3-bis (hydrogen sulphate) sodium salt having molecular weight range of 4000 to 6000 Dalton with special low molecular weight distribution pattern as per the CE of the innovator product i.e. Elmiron ® .
  • This CE is depicted in Fig. 2 and 3.
  • 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 to 50% at pH 6.
  • Pentosan polysulfate sodium is a mixture of linear polymers of ⁇ -1 à 4-linked xylose, usually sulfated at the 2- and 3-positions and occasionally substituted at the 2-position with 4- O -methyl- ⁇ -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 is disclosed in US patent no. 2689848.
  • this process does not provide end product with desired molecular weight.
  • US patent 2689848 disclosed the process for the production of salts of sulfuric acid ester of Xylan, the steps which comprise oxidizing the aqueous solution of the a 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%.
  • Sulfate esters Under-sulfation highly sulfated (sulfate esters) Xylan form a significant therapeutic class of pharmaceuticals in human and veterinary medicine. Sulfate esters demonstrate a broad range of clinical utility in treating various conditions including osteoarthritis, myocardial ischaemia, interstitial cystitis, cancer, and the control and treatment of virus diseases, including human immunodeficiency virus and other retroviruses.
  • Pentosan polysulfate has been used in pharmaceutical formulations to treat osteoarthritis, as an anticoagulant or for other conditions such as interstitial cystitis, transmissible spongiform encephalopathy (TSE) and immunodeficiency virus (such as HIV/AIDS or Feline Immunodeficiency Virus (FIV)) in mammals, such as humans, food-producing and companion animals (such as feline, canine and equine). Pentosan polysulfate may also be used to treat haematomas, haemorrhoids, frostbite, burns, and multiparameter illnesses such as thrombosis and atherosclerosis.
  • TSE transmissible spongiform encephalopathy
  • FV Feline Immunodeficiency Virus
  • Pentosan polysulfate is semisynthetic.
  • the derivation and synthesis of Pentosan polysulfate is proved to be very challenging, with production outcomes being highly variable. This directly relates to inconsistent clinical outcomes. While there are currently no reported clinical trials looking at differences in clinical outcomes of osteoarthritis treatment using more homogenous and more highly sulfated Pentosan polysulfate compared with low sulfated Pentosan polysulfate, anecdotal evidence suggests variability in clinical outcome of low sulfated Pentosan polysulfate. The main reasons that might be behind variability of molecular weight ranges during synthetic process of Pentosan polysulfate is inconsistent and high variation in the degree of sulfation of xylan.
  • Pentosan polysulfate as free acid or in the salt form (typically with inorganic cations such as sodium or calcium) is described in the prior art as a mixture of semi-synthetic polysulfated oligosaccharides, generally obtained from xylan.
  • Pentosan polysulfate consists of sulfated linear 1-4 conjugated beta-D-xylopyranose units and has 4-O-methyl-D-glucuronic acid randomly attached on every eight to ten xylose units (on average).
  • Pentosan polysulfate mixtures typically contain 15 to 17% sulfation. While the prior art describes degrees of sulfation from 15 to 20%, it is apparent from theory and experience that 20% sulfation of Pentosan polysulfate is not theoretically possible unless the sodium is substituted with hydrogen giving Pentosan hydrogen sulfate (in which case maximum sulfation is 21.9%).
  • NMR peak ratios Prior art NMR analyses of sulfate esters (such as US Patent No 4,713,373) use NMR peak ratios to calculate degrees of sulfation. However, NMR peak ratios will not necessarily indicate the degree of sulfation of the molecule unless the calculation is made by analysis of the entire NMR spectrum.
  • Pentosan polysulfate prior art fails to characterise the position of SO 3 ' groups (other than to describe theoretical full sulfation) or to discuss the molecular subspecies. There has been no disclosure in the prior art of where the sulfur is missing along the xylan chain when there is less than full sulfation. The prior art acknowledges that Pentosan polysulfate mixtures differ but focus only on the level of sulfation and average molecular weight as being factors that may significantly affect physiological efficacy of the Pentosan polysulfate material.
  • heparin Studies with heparin show the efficacy of varying molecular species (of heparin) depends on the location of the -OSO 3 groups within the molecule. Specifically, the relationship of chemical structure to activity for heparin is isolated to a pentasaccharide sequence comprising three D-glucosamine and two uronic acid units. The central D-glucosamine unit in this sequence contains a 3-O-sulfate moiety that is rare outside of this sequence. Sulfate groups on the D-glucosamines are found to be critical for retaining high anticoagulant activity, while undersulfation at less important locations seems not to affect the anticoagulant activity.
  • Pentosan polysulfate While use of Pentosan polysulfate became widespread, and to reduce batch to batch variations that could affect pharmaceutical effectiveness, the fundamental problem to overcome was production of a Pentosan polysulfate molecular species with a constant sulfur content close to or at 18 to 19%, with narrow average molecular weight range that ensures consistent physiological benefits and sulfate groups consistently attached to positions that will guarantee physiological effect. To date, there has been no discussion in the prior art regarding the relative importance of the positions of the sulfate groups on the xylan chain.
  • Pentosan polysulfate is derived from natural sources such as xylan. In its natural form, Pentosan polysulfate consists of molecular chains of varying lengths, or molecular weights. However, like heparin, the effects of unfractionated natural Pentosan polysulfate can be difficult to predict.
  • Pentosan polysulfate sodium which provides Pentosan polysulfate with a consistent average molecular weight, consistently low molecular weight and steady but high level of sulfation.
  • It is therefore an 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.
  • Another object of the present invention is to provide the process for the preparation of Pentosan polysulfate of formula (I) or its salt which provides Pentosan polysulfate of formula (I) or its salt with consistent molecular weight of less than 6000 Dalton and with steady but high level of sulfation.
  • Yet another object of the present invention is to provide an improved process for the preparation of Pentosan polysulfate of formula (I) or salt thereof comprising:
  • the present invention provides an improved process for the preparation of Pentosan polysulfate of formula (I) or salt thereof, comprising:
  • Figure-1 depicts capillary electrophoresis pattern of Pentosan polysulfate sodium obtained according to process of present invention.
  • Figure-2 depicts capillary electrophoresis pattern of innovator's Pentosan polysulfate sodium API isolated from Capsule i.e. Elmiron ® .
  • Figure-3 depicts capillary electrophoresis pattern of innovator's Pentosan polysulfate sodium Capsule i.e. Elmiron ® capsule.
  • Xylan is esterified with chlorosulfonic acid in presence of pyridine and Dimethyl form amide to give sulfuric acid ester of Xylan, which is isolated as sodium salt of sulfuric acid ester of Xylan by treatment with sodium hydroxide in methanol.
  • Pentosan Polysulfate sodium Sodium salt of sulfuric acid ester of Xylan is subjected to oxidative depolymerization in presence of hydrogen peroxide and sulfuric acid to give crude Pentosan Polysulfate sodium.
  • the crude Pentosan Polysulfate is isolated by addition of methanol and dried.
  • Pentosan Polysulfate Sodium is resulfonated by pyridine and chlorosulfonic acid in DMF solvent. The material is isolated by methanol and decolorized by chlorine dioxide in water. Pentosan Polysulfate sodium (crude) is purified by reverse osmosis to yield pure Pentosan Polysulfate Sodium, which is isolated by crystallization from methanol.
  • present invention provides an improved process for the preparation of Pentosan polysulfate of formula (I) or salt thereof having Capillary Electrophoresis as depicted in Fig. 1 comprising:
  • the present invention provides an improved process for the preparation of Pentosan polysulfate of formula (I) or salt thereof comprising steps of:
  • alkali' used hereinabove is selected but not limited to alkali metal salt of carbonate, bicarbonate, hydroxide or mixtures thereof. The most preferable is sodium hydroxide.
  • the alcoholic solvent is selected from methanol, ethanol, propanol, isopropanol, butanol or mixtures thereof.
  • the most preferable is methanol.
  • 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 less than of 6000 Dalton.
  • the main advantage of the process of present invention is CE pattern of Pentosan polysulfate sodium obtained according to process of present invention as depicted in Fig. 1 which having molecular weight less than of 6000 Dalton is matches with CE pattern of innovator's Pentosan polysulfate sodium API isolated from Capsule as depicted in Fig. 2 as well as with CE pattern of innovator's Pentosan polysulfate sodium Capsule i.e. Elmiron ® capsule.
  • the isolated product was dissolved in water 500ml and decolorized with chlorine dioxide (400ml), then it was added a mixture of methanol (4000ml) and 33% Sodium hydroxide (400ml). It was then adjusted to pH to neutral with acetic acid, filtered and dried the material at 50-55 0 C under reduced pressure to get 240 gm sodium salt of sulfuric acid ester of xylan.
  • the isolated product was dissolved in water (2125ml) and decolorized with chlorine dioxide (425ml).
  • the reaction mixture pH was adjusted to pH 9.5-10.0 by using 5 N aqueous sodium hydroxide and than stir the reaction mixture for 15 minutes at 25-30°C further the reaction mixture again pH was adjusted to pH 6.5-7.0 by using acetic acid and than reaction mixture was diluted with DM water (10 liter) and charge into feeding tank with system [HPA-400 membrane].
  • the NF Membrane system was monitored the by HPLC till to get the low molecular weight 1.6 to 2.2%. After the completion of filtration, the concentrate was subjected to water recovery at 40-60°C under reduced pressure up to 8500ml.

Landscapes

  • 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)
  • Sustainable Development (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)

Abstract

Cette invention concerne un procédé de préparation amélioré de polysulfate de pentosane de formule (I) ou de son sel. Dans la formule (I), R représente -SO3Y, et Y est au moins un élément choisi dans le groupe constitué par H et un cation de qualité pharmaceutique tel que sodium, potassium, et magnésium qui donne, en particulier, un polysulfate de pentosane très sulfaté (dans ce cas, xylane), de bas poids moléculaire et distribution étroite.
PCT/IB2012/050213 2011-01-29 2012-01-17 Procédé de préparation amélioré de polysulfate de pentosane ou de sels de celui-ci Ceased WO2012101544A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN254MU2011 2011-01-29
IN254/MUM/2011 2011-01-29

Publications (1)

Publication Number Publication Date
WO2012101544A1 true WO2012101544A1 (fr) 2012-08-02

Family

ID=45688918

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2012/050213 Ceased WO2012101544A1 (fr) 2011-01-29 2012-01-17 Procédé de préparation amélioré de polysulfate de pentosane ou de sels de celui-ci

Country Status (1)

Country Link
WO (1) WO2012101544A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
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
US9888679B2 (en) 2007-12-04 2018-02-13 Proteobioactives Pty Ltd Protection of progenitor cells and regulation of their differentiation
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
EP3302705A4 (fr) * 2015-05-27 2019-01-23 Vanguard Therapeutics, Inc. Pentosane polysulfate de sodium pour le traitement de la drépanocytose
WO2020039480A1 (fr) 2018-08-20 2020-02-27 株式会社レクメド Nouvelle préparation de pentosane polysulfate sodique
CN111065654A (zh) * 2016-08-31 2020-04-24 王子控股株式会社 戊聚糖多硫酸酯的生产方法
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
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
US11718609B2 (en) 2016-12-13 2023-08-08 Beta Therapeutics Pty Ltd Heparanase inhibitors and use thereof
US11787783B2 (en) 2016-12-13 2023-10-17 Beta Therapeutics Pty Ltd Heparanase inhibitors and use thereof
WO2024224410A1 (fr) * 2023-04-22 2024-10-31 Rk Pharma Inc Compositions de polysulfate de pentosane de faible poids moléculaire ou de ses sels, et leur procédé de fabrication

Citations (5)

* 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
US4699900A (en) * 1983-03-24 1987-10-13 Sanofi S.A. Xylane sulfates, process for their preparation, and anti-thrombosis and hypolipemic activity thereof
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
WO2008107906A1 (fr) 2007-03-06 2008-09-12 Alembic Limited Processus de préparation de polysulfate de pentosane ou de ses sels
WO2010000013A1 (fr) * 2008-07-04 2010-01-07 Parnell Laboratories (Aust) Pty Ltd Composé polysaccharide sulfaté et sa fabrication et son utilisation

Patent Citations (5)

* 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
US4699900A (en) * 1983-03-24 1987-10-13 Sanofi S.A. Xylane sulfates, process for their preparation, and anti-thrombosis and hypolipemic activity thereof
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
WO2008107906A1 (fr) 2007-03-06 2008-09-12 Alembic Limited Processus de préparation de polysulfate de pentosane ou de ses sels
WO2010000013A1 (fr) * 2008-07-04 2010-01-07 Parnell Laboratories (Aust) Pty Ltd Composé polysaccharide sulfaté et sa fabrication et son utilisation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
OFOSU F A ET AL: "2 Mechanisms of action of low molecular weight heparins and heparinoids", BAILLIERE'S CLINICAL HAEMATOLOGY, BAILLIERE TINDALL, LONDON, GB, vol. 3, no. 3, 1 July 1990 (1990-07-01), pages 505 - 529, XP026166376, ISSN: 0950-3536, [retrieved on 19900701], DOI: 10.1016/S0950-3536(05)80016-2 *

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10609922B2 (en) 2007-12-04 2020-04-07 Proteobioactives Pty Ltd Protection of progenitor cells and regulation of their differentiation
US9888679B2 (en) 2007-12-04 2018-02-13 Proteobioactives Pty Ltd Protection of progenitor cells and regulation of their differentiation
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
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
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
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
EP3302705A4 (fr) * 2015-05-27 2019-01-23 Vanguard Therapeutics, Inc. Pentosane polysulfate de sodium pour le traitement de la drépanocytose
CN111065654B (zh) * 2016-08-31 2022-08-26 王子控股株式会社 戊聚糖多硫酸酯的生产方法
CN111065654A (zh) * 2016-08-31 2020-04-24 王子控股株式会社 戊聚糖多硫酸酯的生产方法
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
US11718609B2 (en) 2016-12-13 2023-08-08 Beta Therapeutics Pty Ltd Heparanase inhibitors and use thereof
US11787783B2 (en) 2016-12-13 2023-10-17 Beta Therapeutics Pty Ltd Heparanase inhibitors and use thereof
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
US11274165B2 (en) 2017-02-28 2022-03-15 Oji Holdings Corporation Pentosan polysulfate, pharmaceutical composition, and 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
WO2024224410A1 (fr) * 2023-04-22 2024-10-31 Rk Pharma Inc Compositions de polysulfate de pentosane de faible poids moléculaire ou de ses sels, et leur procédé de fabrication

Similar Documents

Publication Publication Date Title
WO2012101544A1 (fr) Procédé de préparation amélioré de polysulfate de pentosane ou de sels de celui-ci
WO2008107906A1 (fr) Processus de préparation de polysulfate de pentosane ou de ses sels
WO2009087581A1 (fr) Procédé perfectionné pour la préparation de polysulfate de pentosane ou de ses sels
AU784655B2 (en) Polysaccharidic esters of N-derivatives of glutamic acid
WO1999029734A1 (fr) Derives de dextrane, leur procede de preparation et leurs applications comme medicaments a action biologique specifique
EP0355905B1 (fr) Fragments et fractions d'héparine avec une action contre HIV
CN104231112B (zh) 一种6-o-羧甲基壳聚糖硫酸酯化产物的合成方法
US8513407B2 (en) Process for the preparation of N-acyl-(epi)K5-amine-O-sulfate-derivatives and products thus obtained
HK1254793A1 (zh) 生产高纯度硫酸化ha的改进方法
CN1286852C (zh) 含有自由羟基(oh)或伯胺或仲胺官能团的化合物的磺化方法
ES2584038T3 (es) Sulfato de condroitina similar al de tiburón, y procedimiento para la preparación del mismo
NZ537216A (en) Process for the manufacture of N-acyl-(epi)K5-amine-O-sulfate-derivatives and products thus obtained
IE833063L (en) Process for the depolymerisation and sulfation of¹polysaccharides
WO2018220514A1 (fr) Dérivés de polysaccharides hydrosolubles, leur procédé de préparation et leurs utilisations
US20230151121A1 (en) Chitosan derivatives and methods for preparing the same
AU2006248966A1 (en) Antiproliferative conjugates comprising hyaluronic acid and N-derivatives of glutamic acid
EP1411956B1 (fr) Utilisation de polysaccharides sursulfates comme inhibiteurs du hiv
GB2262531A (en) Antiviral sulphated polysaccharides
RU2283320C1 (ru) Способ получения модифицированных гликозаминогликанов, обладающих анальгезирующими свойствами
GB796737A (en) A process for the production of glycan poly-(sulphuric acid esters)
ZA200410357B (en) Process for the manufacture on N-acyl-(EPI)K5-amine-o-sulfate-derivatives and products thus obtained.
KR20050024339A (ko) 엔-아실-(에피)케이5-아민-오-황산염-유도체 생산방법 및그 생성물

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12704909

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 12704909

Country of ref document: EP

Kind code of ref document: A1