EP2328935A1 - Polysaccharide mit antithrombotischer wirkung, die eine kovalente bindung und eine aminokette enthalten - Google Patents

Polysaccharide mit antithrombotischer wirkung, die eine kovalente bindung und eine aminokette enthalten

Info

Publication number
EP2328935A1
EP2328935A1 EP09737025A EP09737025A EP2328935A1 EP 2328935 A1 EP2328935 A1 EP 2328935A1 EP 09737025 A EP09737025 A EP 09737025A EP 09737025 A EP09737025 A EP 09737025A EP 2328935 A1 EP2328935 A1 EP 2328935A1
Authority
EP
European Patent Office
Prior art keywords
group
formula
oso
polysaccharides
pharmaceutically acceptable
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.)
Withdrawn
Application number
EP09737025A
Other languages
English (en)
French (fr)
Inventor
Joseph Schofield
Dave Smith
Patrick Soubayrol
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.)
Sanofi SA
Original Assignee
Sanofi Aventis France
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 Sanofi Aventis France filed Critical Sanofi Aventis France
Publication of EP2328935A1 publication Critical patent/EP2328935A1/de
Withdrawn legal-status Critical Current

Links

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
    • C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
    • C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
    • C08B37/0075—Heparin; Heparan sulfate; Derivatives thereof, e.g. heparosan; Purification or extraction methods thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to novel synthetic oligomers and polysaccharides having at least one covalent linkage with an amino chain and having the anticoagulant and antithrombotic pharmacological activities of heparin.
  • the patent application WO 02/24754 describes synthetic polysaccharides which have a covalent bond with biotin (hexahydro-2-oxo-7H-thieno [3,4-d] imidazole-4-pentanoic acid) or with a derivative of biotin.
  • biotin hexahydro-2-oxo-7H-thieno [3,4-d] imidazole-4-pentanoic acid
  • Such polysaccharides have antithrombotic activity which makes them usable as anticoagulants and have, in addition, the advantage of being able to be quickly neutralized by a specific antidote, in an emergency situation.
  • This specific antidote is avidin (The Merck Index, Twelfth edition, 1996, MN 920, pages 151-152) or streptavidin, two tetrameric proteins of respective masses equal to about 66,000 and 60,000 Da, which possess a very strong affinity for biotin.
  • the invention therefore relates to synthetic polysaccharides with antithrombotic activity having at least one covalent bond with an amino chain of formula -NH-CO- (CH 2 ) 5 -NH 2 .
  • the subject of the present invention is the polysaccharides of formula (I):
  • the wavy line designates a link situated either below or above the plane of the pyranosic cycle
  • h 1 or 2
  • n is an integer and can take any value from 0 to 25,
  • R 1 represents a group -NH-CO- (CH 2 ) S -NH 2 , a group (C 1 -C 6 JaClOXy) or a group -OSO 3 " ,
  • R 2 represents a group -NH-CO- (CH 2 ) 5 -NH 2 , a group (C 1 -C 6 JaClOXy) or a group -OSO 3 '
  • R 3 represents a group -NH-CO- (CH 2 ) S -NH 2 or a group (C 1 -C 6 JaClOXy
  • R 4 represents a group -NH-CO- (CH 2 ) 5 -NH 2 , a group (C 1 -C 6 JaClOXy) or a group -OSO 3 " or else R 4 constitutes a bridge -O-CH 2 -, the group -CH 2 - being bonded to the carbon atom carrying the carboxylic function on the same ring, it being understood that at least one of the substituents R 1 , R 2 , R 3 or R 4 represents a group -NH -CO- (CH 2 ) 5 -NH 2 ,
  • - W represents an oxygen atom or a methylene group, and their pharmaceutically acceptable salts.
  • a wavy line designates a link located either below or above the plane of the pyranosic cycle.
  • the monosaccharides contained in Po may be identical or different from one another, the interglycosidic bonds may be of the ⁇ or ⁇ type.
  • the polysaccharide portion Po may consist of from 0 to 25 monosaccharide units alkylated and di- or trisulfated.
  • the polysaccharide part Po may also consist of from 0 to 25 monosaccharide mono- saccharide units and mono- or disulfated.
  • the polysaccharide portion Po may consist of from 0 to 25 unloaded and / or partially charged and / or fully charged alkylated monosaccharide units.
  • the charged or uncharged units may be dispersed throughout the chain or they may instead be grouped into charged or uncharged saccharide domains.
  • the links between the units can be 1, 2; 1, 3; 1, 4; 1, 5; 1, 6; and of the ⁇ or ⁇ type.
  • L-iduronic acid may be 1 C 4 2 S 0 or 4 C 1 conformation.
  • the invention relates to the polysaccharides of formula (1.1):
  • the groups R 1 are as defined for (I) and, for the same monosaccharide, may be identical or different, the monosaccharide contained in [] m is repeated m times, the monosaccharide contained in [] t is repeated t times , the monosaccharide contained in [] p is repeated p times, m is an integer varying from 1 to 5, t is an integer varying from 0 to 24 and p is an integer varying from 0 to 24, provided that 1 ⁇ m + 1 + p ⁇ 25, as well as their pharmaceutically acceptable salts.
  • polysaccharides of formula (1.1) polysaccharides in which only one of the substituents R 1 , R 2 , R 3 or R 4 represents a group -NH-CO- (CH 2 ) S -NH 2 , as well as their pharmaceutically acceptable salts acceptable, constitute a subgroup of the invention.
  • the invention relates to hexadecasaccharides of formula (1.2):
  • - T represents a group -NH-CO- (CH 2 ) 5 -NH 2
  • - Pe represents a pentasaccharide of structure:
  • R 1 represents a group (C 1 -C 6 JaClOXy or a group -OSO 3 " ,
  • R 2 represents a group (C 1 -C 6 JaClOXy or a group -OSO 3 " ,
  • R 3 represents a group (C r C 6 ) alkoxy
  • R 4 represents a group (CrC 6 ) alkoxy or a group -OSO 3 " , or R 4 constitutes a bridge -O-CH 2 -, the group -CH 2 - being bonded to the carbon atom carrying the carboxylic function on the same cycle,
  • W represents an oxygen atom or a methylene group, as well as their pharmaceutically acceptable salts.
  • the invention relates to the pentasaccharides of formula (1.3):
  • R 1 , R 2 , R 3 , R 4 and W are as defined for (I), as well as their pharmaceutically acceptable salts.
  • pentasaccharides of formula (1.3) pentasaccharides in which only one of the substituents R 1 , R 2 , R 3 or R 4 represents a group -NH-CO- (CH 2 ) 5 -NH 2 , as well as their pharmaceutically acceptable salts acceptable, constitute a subgroup of the invention.
  • pentasaccharides of formula (1.3) the subject of the invention is also the pentasaccharides of formula (1.4):
  • T represents a group -NH-CO- (CH 2 ) 5 -NH 2 ,
  • R 1 represents a group (C 1 -C 6 JaClOXy or a group -OSO 3 " ,
  • R 2 represents a group (C 1 -C 6 JaClOXy) or a group -OSO 3 '
  • - R 3 represents a group (C 1 -C 6 ) BlCOXy
  • - R 4 represents a group (C 1 -C 6 JaClOXy) or a group -OSO 3 '
  • R 4 constitutes a bridge -O-CH 2 -, the group -CH 2 - being bonded to the carrier carbon atom of the carboxylic function on the same cycle
  • - W represents an oxygen atom or a methylene group, and their pharmaceutically acceptable salts.
  • the invention relates to the following polysaccharide: Methyl (2- [N- (6-aminohexanoyl)] - 2-deoxy-3,4-di-O-methyl-6-O-sulfonato- ⁇ -D-glucopyranosyl) - (1 - ⁇ 4) - (2,3-di-O-methyl- ⁇ -D-glucopyranosyluronic acid) - (1 ⁇ 4) - (2,3,6-tri-O-sulfonato) - ⁇ -D-glucopyranosyl) - (1 ⁇ 4) - (2,3-di-O-methyl- ⁇ -L-idopyranosyluronic acid) - (1 ⁇ 4) -2,3,6-tri-O- sulfonato- ⁇ -D-glucopyranoside, sodium salt.
  • the invention includes polysaccharides in their acid form or in the form of any of their pharmaceutically acceptable salts.
  • the -COO ' and -SO 3 "functions are respectively in the form of -COOH and -SO 3 H.
  • salt polysaccharides of the invention, a polysaccharide in which one or more of -COO - and / or -SO 3 - functions are ionically bonded to a pharmaceutically acceptable cation.
  • the preferred salts according to the invention are those whose cation is chosen from alkali metal cations and more preferably still those whose cation is Na + or K + .
  • the compounds of formula (I) above also include those in which one or more hydrogen or carbon atoms have been replaced by their radioactive isotope, for example tritium or carbon-14. Such labeled compounds are useful in research, metabolism or pharmacokinetics, in biochemical assays as ligands.
  • the process for preparing the compounds according to the invention uses di- or oligosaccharide base synthons prepared as previously reported in the literature.
  • These synthons are then coupled to each other so as to provide a fully protected equivalent of a polysaccharide according to the invention. This protected equivalent is then converted into a compound according to the invention.
  • One of the basic synthons mentioned above contains a particular protected function allowing the subsequent introduction of the group -CO- (CH 2 ) S -NH 2 (so as to form the chain -NH-CO- (CH 2 ) 5 -NH 2 on the polysaccharide), for example a latent amine function in the form of an azido group or protected in the form of N-phthalimido.
  • a "donor" di- or oligosaccharide activated on its anomeric carbon, reacts with a "acceptor” di- or oligosaccharide having a free hydroxyl.
  • the present invention relates to a process for the preparation of compounds of formula (I) characterized in that: in a first step, a completely protected equivalent of the desired polysaccharide (I), containing a protected precursor of the domain Pe extended at its non-reducing end by a protected precursor of the sulphated polysaccharide Po is synthesized, one of these precursors containing in particular a suitably protected amino function for the subsequent introduction of the -CO- (CH 2 ) 5 -NH 2 group , itself suitably protected; in a second step, the negatively charged groups are introduced and / or unmasked; in a third step, the amine function is deprotected on the polysaccharide and then the -CO- (CH 2 ) 5 -NH 2 protected group is introduced; in a fourth step, the NH 2 terminal group is unmasked.
  • the synthesis of Pe is carried out according to the methods described in particular in the patent applications published under the numbers WO 98/03554 and WO 99/36443, as well as
  • the synthesis of the polysaccharide precursor part of Po is carried out according to reactions well known to those skilled in the art, using the methods of oligosaccharide synthesis (GJ Boons, Tetrahedron, 1996, 52, 1095-1121, WO 98/03554 and WO 99/36443).
  • a glycosidic link donor oligosaccharide is coupled with a glycosidic link acceptor oligosaccharide to yield another oligosaccharide the size of which is equal to the sum of the sizes of the two reactive species. This sequence is repeated until the desired compound of formula (I) is obtained.
  • the nature and the charge profile of the desired final compound determine the nature of the chemical entities used in the various steps of the synthesis, according to the rules well known to those skilled in the art.
  • the compounds of the invention are obtained from their completely protected polysaccharide precursors using the following sequence of reactions:
  • the alcohol functions to be converted into an O-sulpho group and the carboxylic acids are deprotected by the elimination of the protective groups used during the development of the skeleton,
  • the suitably protected -CO- (CH 2 ) 5 -NH 2 group is introduced by a conventional amino / acid coupling reaction, and then
  • the compounds of the invention can naturally be prepared using various strategies known to those skilled in the art of oligosaccharide synthesis.
  • the process described above is the preferred method of the invention.
  • the compounds of formula (I) can be prepared by other well known methods of the chemistry of sugars described for example in Monosaccharides, Their chemistry and their roles in natural products, PM Collins and RJ. Ferrier, J. Wiley & Sons, 1995 and in GJ. Boons, Tetrahedron, 1996, 52, 1095-1121.
  • the pentasaccharides Pe can thus be obtained from disaccharide synthons in the manner described in the publication by C. van Boeckel, M. Petitou, Angew. Chem. Int. Ed. Engl., 1993, 32, 1671-1690.
  • the protecting groups used in the process for the preparation of compounds (I) are those commonly used in the chemistry of sugars, as described, for example, in Protective Groups in Organic Synthesis, TW Greene, John Wiley & Son, New York, 1981.
  • the protecting groups may for example be selected from acetyl, halomethyl, benzoyl, levulinyl, benzyl, substituted benzyl, optionally substituted trityl, tetrahydropyranyl, allyl, pentenyl, tert-butyldimethylsilyl (tBDMS) or trimethylsilylethyl groups.
  • Activator groups are those conventionally used in sugar chemistry according to GJ for example.
  • the introduction of the -CO- (CH 2 ) S -NH 2 group onto the free amine function of the polysaccharide can be carried out using an Act-CO type reagent.
  • Act represents an activating group of an acid function (such as an imide, for example a succinimide derivative, or a mixed anhydride, or any other agent known activator in peptide chemistry for amino / acid coupling reactions) and
  • Pg represents an amine protecting group (such as a benzyloxycarbonyl group).
  • the process described above makes it possible to obtain the compounds of the invention in the form of salts.
  • the compounds of the invention in the form of salts are contacted with a cation exchange resin in acid form.
  • the compounds of the invention in the form of acids can then be neutralized with a base to obtain the desired salt.
  • any inorganic or organic base can be used, giving with the compounds of formula (I), pharmaceutically acceptable salts.
  • Sodium, potassium, potassium hydroxide is preferably used as the base. calcium or magnesium.
  • the sodium and calcium salts of the compounds of formula (I) are the preferred salts.
  • the grafting of the amino chain is carried out on pentasaccharide 44, or methyl (2-amino-2-deoxy-3,4-di-O-methyl-6-O-sulfonato- ⁇ -D-glucopyranosyl) - (1 ⁇ 4) - (2,3-di-O-methyl- ⁇ -D-glucopyranosyluronic acid) - (1-> 4) - (2,3,6-tri-O-sulfonato- ⁇ -D-glucopyranosyl) - (1 ⁇ 4) - (2,3-di-O-methyl- ⁇ -L-idopyranosyl-uronic acid) - (1 ⁇ 4) - 2,3,6-tri-O-sulfonemono- ⁇ - D-glucopyranoside, sodium salt, the preparation of which is described in patent application WO 02/24754:
  • the solid residue is triturated with 2-propanol (10 mL) and the suspension centrifuged for 5 minutes at 2500 rpm.
  • the alcohol phase is withdrawn and replaced by 2-propanol (10 mL) and the centrifugation is repeated. After withdrawing the solvent, the crude product is dried under vacuum.
  • Proton NMR at 200 MHz in deuterated water The structure of the expected product is confirmed, since the spectrum obtained is identical to that produced on a product synthesized according to Example 5 of patent application WO 02/24754. , without the signals due to the atoms of the biotin part but with signals from 7.4 to 7.5 ppm due to the benzyloxy group.
  • the product obtained after the previous step (399 mg) is dissolved in deuterated water (10 mL).
  • the solution is treated with 10% palladium on carbon (25 mg) and the solution is stirred for 20 hours in the presence of hydrogen at atmospheric pressure.
  • the mixture is diluted with water (15 mL), the catalyst is filtered and the solution is washed with chloroform (2 x 15 mL) and evaporated to dryness under reduced pressure.
  • An aliquot (98 mg on 320 mg) of this product is purified on a column of Sephadex G-25 gel (2.5 x 50 cm) with water as eluent to give 25 mg of compound 1.
  • the compounds according to the invention have been the subject of biochemical and pharmacological studies.
  • IC 50 1.69 ⁇ 10 -2 ⁇ g / ml (IC 50: dose allowing a 50% inhibition).
  • the oligosaccharides of the present invention constitute very interesting drugs. Their toxicity is perfectly compatible with this use. They are also very stable and are therefore particularly suitable for constituting the active principle of pharmaceutical specialties.
  • thromboembolic disorders associated with atherosclerosis and diabetes such as unstable angina, cerebral attack, restenosis after angioplasty, endarterectomy, placement of endovascular prostheses; or thromboembolic disorders associated with rethrombosis after thrombolysis, infarction, dementia of ischemic origin, peripheral arterial diseases, hemodialysis, atrial fibrillation, or the use of aortic bypass graft vascular prostheses. -coronariens.
  • These products can also be used for the treatment or prevention of venous thromboembolic pathologies, such as pulmonary embolism and deep vein thrombosis. They can be used or to prevent or treat thrombotic complications observed for example as a result of surgical operations, tumor development or disruption of coagulation, induced by bacterial, viral or enzymatic activators.
  • the compounds of the present invention can cover prostheses and thus make them hemocompatible.
  • they can be attached to intravascular prostheses (stents).
  • they may optionally be chemically modified by introduction to the non-reducing or reducing end of a suitable arm, as described in EP 649854.
  • the compounds of the present invention may also be used as adjuvants during endarterectomy performed with porous balloons.
  • the compounds of the invention may be used for the preparation of medicaments for treating or preventing the above diseases.
  • the subject of the present invention is therefore a pharmaceutical composition containing, as active ingredient, a synthetic polysaccharide according to the invention or a pharmaceutically acceptable salt thereof, optionally in combination with one or more inert excipients. and appropriate.
  • Said excipients are chosen according to the desired pharmaceutical form and mode of administration: oral, sublingual, subcutaneous, intramuscular, intravenous, transdermal, transmucosal, local or rectal.
  • the active ingredient may also be presented in the form of a complex with a cyclodextrin, for example ⁇ , ⁇ or ⁇ -cyclodextrin, 2-hydroxypropyl- ⁇ -cyclodextrin or methyl- ⁇ -cyclodextrin.
  • the active ingredient can also be released by a balloon containing it or by an endovascular stent introduced into the blood vessels. The pharmacological effectiveness of the active ingredient is thus not affected.
  • each dosage unit the active ingredient is present in the appropriate amounts in order to obtain the desired prophylactic or therapeutic effect.
  • Each dosage unit may contain from 0.1 to 100 mg of active ingredient, preferably 0.5 to 50 mg, more preferably 2.5 to 3.0 mg.
  • the compounds according to the invention may also be used in combination with one or more other active ingredients that are useful for the desired therapy, such as, for example, antithrombotics, anticoagulants, antiplatelet agents such as, for example, dipyridamole, aspirin or ticlopidine. , clopidogrel or antagonists of the glycoprotein Ilb / IIIa complex.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Polymers & Plastics (AREA)
  • Materials Engineering (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Hematology (AREA)
  • Hospice & Palliative Care (AREA)
  • Urology & Nephrology (AREA)
  • Diabetes (AREA)
  • Psychiatry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Materials For Medical Uses (AREA)
  • Polysaccharides And Polysaccharide Derivatives (AREA)
EP09737025A 2008-08-26 2009-08-24 Polysaccharide mit antithrombotischer wirkung, die eine kovalente bindung und eine aminokette enthalten Withdrawn EP2328935A1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR0804704A FR2935386B1 (fr) 2008-08-26 2008-08-26 Nouveaux polysaccharides a activite antithrombotique comprenant une liaion covalente avec une chaine amine
PCT/FR2009/001023 WO2010023374A1 (fr) 2008-08-26 2009-08-24 Polysaccharides a activite antithrombotique comprenant une liaison covalente avec une chaine amine

Publications (1)

Publication Number Publication Date
EP2328935A1 true EP2328935A1 (de) 2011-06-08

Family

ID=40521663

Family Applications (1)

Application Number Title Priority Date Filing Date
EP09737025A Withdrawn EP2328935A1 (de) 2008-08-26 2009-08-24 Polysaccharide mit antithrombotischer wirkung, die eine kovalente bindung und eine aminokette enthalten

Country Status (5)

Country Link
US (1) US8492352B2 (de)
EP (1) EP2328935A1 (de)
JP (1) JP2012500884A (de)
FR (1) FR2935386B1 (de)
WO (1) WO2010023374A1 (de)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2614089A1 (de) 2010-09-10 2013-07-17 Sanofi-Aventis Biotinylierte polysaccharide mit antithrombotischer wirkung und erhöhter stoffwechselstabilität
AU2017321817B2 (en) 2016-08-31 2022-12-15 Oji Holdings Corporation Production method for acidic xylooligosaccharide, and acidic xylooligosaccharide
JP6225321B1 (ja) 2016-08-31 2017-11-08 王子ホールディングス株式会社 ポリ硫酸ペントサンの製造方法
JP6281659B1 (ja) 2017-02-28 2018-02-21 王子ホールディングス株式会社 ポリ硫酸ペントサン、医薬組成物及び抗凝固剤
SG11201911318SA (en) 2017-05-31 2020-01-30 Oji Holdings Corp Moisturizing topical preparation
WO2019054344A1 (ja) * 2017-09-12 2019-03-21 王子ホールディングス株式会社 ポリ硫酸ペントサン及びポリ硫酸ペントサンの製造方法
CN111511773B (zh) 2017-12-20 2023-01-13 王子控股株式会社 戊聚糖多硫酸酯以及含有戊聚糖多硫酸酯的药物
CN112717207A (zh) * 2020-12-15 2021-04-30 山东大学 一种基于仿生多巴胺的长效抗菌多功能涂层及其制备方法和应用
CN113616861A (zh) * 2021-08-03 2021-11-09 广州维力医疗器械股份有限公司 逐层自组装复合抗凝血涂层、其制备方法及医疗器械

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2751334B1 (fr) * 1996-07-19 1998-10-16 Sanofi Sa Polysaccharides synthetiques, procede pour leur preparation et compositions pharmaceutiques les contenant
FR2773804B1 (fr) * 1998-01-19 2000-02-18 Sanofi Sa Polysaccharides de synthese, procede pour leur preparation et compositions pharmaceutiques le contenant
FR2814463B1 (fr) * 2000-09-22 2002-11-15 Sanofi Synthelabo Nouveaux polysaccharides a activite antithrombotique comprenant au moins une liaison covalente avec la biotine ou un derive de la biotine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2010023374A1 *

Also Published As

Publication number Publication date
FR2935386B1 (fr) 2010-09-10
JP2012500884A (ja) 2012-01-12
US8492352B2 (en) 2013-07-23
US20110306567A1 (en) 2011-12-15
FR2935386A1 (fr) 2010-03-05
WO2010023374A1 (fr) 2010-03-04

Similar Documents

Publication Publication Date Title
EP1322673B1 (de) Polysaccharide mit antithrombotischer wirkung, die mit biotin oder einem biotenderivat kovalent gebunden sind
EP2328935A1 (de) Polysaccharide mit antithrombotischer wirkung, die eine kovalente bindung und eine aminokette enthalten
EP0214879B1 (de) Verfahren zur Sulphatierung von Glykosaminoglykanen, daraus hergestellte Glykosaminoglykane und ihre biologischen Verwendungen
CA2501546C (fr) Melanges de polysaccharides derives d'heparine, leur preparation et les compositions pharmaceutiques les contenant
EP0912613B1 (de) Synthetische polysaccharide, verfahren zu deren herstellung und diese enthaltende, pharmazeutische zusammensetzungen
EP1791872B1 (de) Biotinylierte hexadecasaccharide, pharmazeutische zusammensetzungen daraus und deren verwendung
EP1049721B1 (de) Synthetische polysaccharide, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzungen
EP0356275A1 (de) Selektiv O-acylierte Glycosaminoglykane
EP0165134B1 (de) Oligosaccharide, ihre Herstellung durch Synthese und ihre biologische Verwendung
EP1049706B1 (de) Pentasaccharide, verfahren zu ihrer herstellung und pharmazeutische zubereitungen die sie enthalten
EP0904299A1 (de) Synthetische polysaccharide, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzungen
CA2678166A1 (fr) Heparines comprenant au moins une liaison covalente avec la biotine ou un derive de la biotine, leur procede de preparation et leur utilisation
WO2010023375A1 (fr) Hexadecasaccharides a activite antithrombotique comprenant une liaison covalente avec une chaine amine
EP0138632B1 (de) Komplexe, welche Oligosaccharide enthalten, ihre Herstellung und ihre biologische und biochemische Verwendung
EP2614089A1 (de) Biotinylierte polysaccharide mit antithrombotischer wirkung und erhöhter stoffwechselstabilität
FR2964660A1 (fr) Nouveaux polysaccharides biotinyles a activite antithrombotique et presentant une stabilite metabolique amelioree
FR2531436A1 (fr) Pentasaccharides substitues possedant des proprietes biologiques, leur preparation et leurs applications en tant que medicaments
JPH0228192A (ja) 新規オリゴ糖及びその製造方法

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20110328

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR

AX Request for extension of the european patent

Extension state: AL BA RS

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: SANOFI

DAX Request for extension of the european patent (deleted)
RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: SANOFI

RAP1 Party data changed (applicant data changed or rights of an application transferred)

Owner name: SANOFI

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20150303