WO2004026278A1 - Nouveaux composes a base de copolymere et d'hemoproteine et leurs applications - Google Patents
Nouveaux composes a base de copolymere et d'hemoproteine et leurs applications Download PDFInfo
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- WO2004026278A1 WO2004026278A1 PCT/FR2003/001435 FR0301435W WO2004026278A1 WO 2004026278 A1 WO2004026278 A1 WO 2004026278A1 FR 0301435 W FR0301435 W FR 0301435W WO 2004026278 A1 WO2004026278 A1 WO 2004026278A1
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- compounds according
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- hemoprotein
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- hemoglobin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0026—Blood substitute; Oxygen transporting formulations; Plasma extender
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/41—Porphyrin- or corrin-ring-containing peptides
- A61K38/42—Haemoglobins; Myoglobins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
- A61K47/6929—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
- A61K47/6931—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
- A61K47/6935—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
- A61K47/6929—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
- A61K47/6931—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
- A61K47/6939—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
Definitions
- the invention relates to new compounds based on copoly eres with a sequenced structure comprising a hydrophilic segment linked to at least one hydrophobic segment, and their applications in particular for the preparation of blood substitutes and as depolluting agents.
- Perfluorocarbons are halogenated fatty acids which have the property of increasing the solubility of oxygen in an aqueous medium; hemoglobin solutions consist of polymerized hemoglobin.
- copolymers previously developed, usable as vectors of active principle, were capable of generally associating hemoproteins, in amounts of the order of at least 25 mg of hemoglobin per gram of polymer, which gives them great interest as oxygen transporters.
- hemoprotein as used in the invention includes normal hemoproteins, such as cytochromes, myoglobins, as well as modified hemoproteins, in particular natural or modified hemoglobins, for example bridged, polymerized, mutated or comprising chains. more or less long peptides.
- the invention also extends to hemoprotein analogs in which iron is substituted by another metal, for example by cobalt, magnesium, copper or zinc.
- such substitutes have " great stability. A significant part of the associated hemoprotein molecule remains in effect attached to the copolymer after treatment with surfactants.
- the invention therefore aims to provide, as new products, compounds of said copolymers with hemoproteins.
- the compounds of the invention are characterized in that they comprise a hemoprotein associated with a block block copolymer, comprising a hydrophilic segment of oligo or polysaccharide linked to at least one hydrophobic segment of formula
- - X represents H or an alkyl radical
- - Y represents a radical COOR ', CONHR "or C 6 H 5 , with R, R' and R" representing, independently of one another, an atom of hydrogen, a linear or branched C- L alkyl group, a linear or branched C1-C alkoxy group, an amino acid radical, a mono- or poly-hydroxylated acid radical or a C 5 aryl or heteroaryl radical to Ci ?, and the forms associated with a gas.
- the hemoprotein is natural or modified. It is more specifically hemoglobin, where appropriate recombinant.
- copolymers are in particular described in application WO 02/39979 published on May 23, 2002, on behalf of the CNRS (inventors Chauvierre et al). They are in the form of particles from 1 nia to 1 mm.
- said hydrophilic segment is linked by one of its ends to a single hydrophobic segment of formula (I), or by each of its two ends at a hydrophobic segment, the two hydrophobic segments being identical or different.
- X preferably represents a CN radical and Y an ester radical.
- Copolymers especially advantageous for the implementation of such applications include, as hydrophobic segment, pol (alkyl cyanoacryiates).
- X is advantageously H and Y a phenyl or ester radical.
- the hydrophilic segment of saccharide nature is a natural or synthetic oligo or polysaccharide, modified or not, as defined in application WO 02/39979. It is advantageously dextran, optionally sulfated, or heparin.
- the copolymers of the invention are in the form of particles from 1 n to 1 mm.
- the copolymers are in the form of nanoparticles of said compounds.
- These nanoparticles can be obtained according to the polymerization technique allowing the assembly by covalent bond of at least one hydrophobic segment of general formula (I) with a natural or modified oligo and / or polysaccharide segment, in particular according to the radical polymerization technique described in said application WO 02/39979.
- the core of the nanoparticles made up of the hydrophobic amorphous polymer allows the loading of hydrophobic compounds, such antioxidants, which limits the percentage of methemoglobin formation.
- the structure of the compounds makes it possible to avoid their capture by the non-specific immune defense system of the organism and, therefore, ensures their prolonged circulation in the circulatory current.
- the gas-associated forms of the compounds of the invention also fall within the scope of the invention.
- the invention relates in particular to associations with oxygen.
- the preparation of the compounds of the invention comprises contacting a colloidal suspension of said nanoparticles with a solution of r hemoprotein, for a time sufficient to obtain the combination of 1 'hemoprotein, advantageously followed by a purification step .
- the compounds of the invention do not exhibit toxicity in humans. It will also be noted with interest that sizes of the order of a nanometer allow the particles to access the vascular microcirculation. These products are non-munogenic, bioerodible and stable.
- the invention therefore relates to the biological applications of these compounds, especially as substitutes for human or animal blood.
- the nanoparticle development technology makes it possible to vary the size of the compounds, but also the composition of the polysaccharides on the surface of the nanoparticles. It is thus possible with a view to transfusion use, to choose polysaccharides endowed with properties. that may facilitate or target the supply of oxygen to the tissues concerned.
- the product will be indicated to treat a hemorrhagic syndrome, an occlusive vascular accident or as an adjuvant to an anti-tumor therapy, for example as a radiosensitizer.
- heparin-coated vectors have the advantage of combining hemoglobin, while retaining the anticoagulant properties of heparin. This blood substitute is therefore more particularly suitable for vasoocclusive accidents.
- the raw materials for preparing the substitutes of the invention, and their processes for obtaining them are inexpensive and that it is possible to produce large quantities of them.
- the invention is of great interest in the medical field since the market for blood substitutes is global, that demand is continuously growing and that this market is still awaiting an effective blood substitute without side effects.
- the invention also relates to pharmaceutical compositions characterized in that they contain a therapeutically effective amount of at least one compound in the form of nanoparticles as defined above, in combination with a pharmaceutically acceptable vehicle.
- These compositions will be administered in dosages adapted to the emergency situation and to the pathology to be treated, which will be easily determined by a person skilled in the art.
- These compositions are in the form of injectable solutions. These are more particularly compositions in which the nanoparticles are in a physiological serum.
- the invention further relates to the use of the compounds defined above as agents for the depollution of gases, such as carbon monoxide or nitrogen.
- Example 1 Nanoparticles from a copolymer consisting of dextran and poly (isobutyl cyanoacrylate) (PIBCA).
- PIBCA poly (isobutyl cyanoacrylate)
- Dialysis bags (Spectra / Por® CE MWCO: 100,000) are regenerated for 30 minutes with osmosis water. Colloidal suspensions passed through the vortex are introduced into the regenerated bags.
- Example 2 Nanoparticles from a copolymer of heparin and pol (isobutyl cyanoacrylate).
- Example 3 Nanoparticles from a copolymer of heparin, dextran and poly (isobutyl cyanoacrylate). The same protocol as that described in example 1 is reproduced using 0.0688 g of heparin and 0.6688 g of dextran in place of 0.1375 g of dextran.
- Example 4 Nanoparticles from a copolymer of dextran sulfate and of poly (isobutyl cyanoacrylate).
- the same protocol ⁇ as that described in example 1 is reproduced using 0.1375 g of dextran sulphate of variable molar mass (10,000 and 40,000 g / mol) in place of dextran.
- Example 5 Concentration of the colloidal suspensions.
- the colloidal suspensions can optionally be concentrated by ultrafiltration on an AMICON cell equipped with an Oga membrane of 300 kD.
- Example 6 Step of association of hemoglobins on the various nanoparticles.
- the colloidal suspension (1 ml) is brought into contact overnight with variable volumes (from 25 to 100 ⁇ l) of normal or bridged adult hemoglobin solution at 100 mg / ml and balanced under carbon onoxide at 10-th .
- the colloidal suspensions loaded with hemoglobin (1 ml) are isolated by filtration on a Sephacrvl® S100 column (60 cm long) balanced in 100 mM sodium phosphate buffer, pH 7.4.
- the fluids comprising the nanoparticles are then ultrafiltered on an AMICON cell equipped with a 300 kD Omega membrane and rinsed with 4 ml of 100 mM sodium phosphate solution, 150 M Na Cl, pH 7.4.
- the ultrafiltered nanoparticles are taken up in 1 ml of 100 mM sodium phosphate buffer, 150 mM Na Cl, pH 7.4.
- Example 7 Determination of the amount of associated hemoglobin on the various nanoparticles.
- Example 8 Determination of the size of the various nanoparticles.
- the size of the nanoparticles is checked by quasi-elastic light scattering, after synthesis and purification of the latter, then after fixation of the hemoglobins.
- the nanoparticle suspensions are diluted in MilliQ® water so that the number of particles per ml is suitable for the measuring equipment.
- Example 9 Functional studies of associated hemoglobins on nanoparticles.
- the dynamic properties of a functional hemoglobin are controlled " " in the hemoglobin-CO form (after ' reduction by dithionite and association of carbon monoxide at 10%) by flash photolysis and by the static spectral properties between 710 nm and 380 nm.
- Example 10 Determination of the surface charges of nanoparticles loaded with hemoglobin.
- the nanoparticle suspensions loaded with hemoglobin are diluted 1/200 ° in a solution of Na Cl at 1 mM, then analyzed using a zeta.
- Example 11 Studies of the function of polysaccharides on the surface of nanoparticles after their loading in hemoglobin.
- Nanoparticulate suspensions loaded with hemoglobin and having heparin on their surface are subjected to the von Willebrandt factor binding test.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Nanotechnology (AREA)
- Immunology (AREA)
- Optics & Photonics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Dermatology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Diabetes (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/533,084 US20060182807A1 (en) | 2002-09-17 | 2003-06-10 | Copolymer and hemoprotein based novel compounds and uses thereof |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0211518A FR2844512B1 (fr) | 2002-09-17 | 2002-09-17 | Nouveaux composes a base de copolymeres et leurs applications |
FR02/11518 | 2002-09-17 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2004026278A1 true WO2004026278A1 (fr) | 2004-04-01 |
Family
ID=31897452
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/FR2003/001435 WO2004026278A1 (fr) | 2002-09-17 | 2003-06-10 | Nouveaux composes a base de copolymere et d'hemoproteine et leurs applications |
Country Status (3)
Country | Link |
---|---|
US (1) | US20060182807A1 (fr) |
FR (1) | FR2844512B1 (fr) |
WO (1) | WO2004026278A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009034458A2 (fr) * | 2007-09-11 | 2009-03-19 | Universität Basel | Nanorécipients polymères perméables à l'oxygène utilisables en vue de l'encapsulation de composés sensibles |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102008045152A1 (de) * | 2008-07-09 | 2010-01-14 | Universität Duisburg-Essen | Künstliche Sauerstoffträger und ihre Verwendung |
AU2018304174A1 (en) | 2017-07-18 | 2020-02-06 | VirTech Bio, Inc. | Blood substitutes comprising hemoglobin and methods of making |
WO2023048002A1 (fr) * | 2021-09-24 | 2023-03-30 | 三菱鉛筆株式会社 | Dispersion de particules réductrices |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5670173A (en) * | 1992-09-14 | 1997-09-23 | Mcgill University | Biodegradable polymer membrane containing hemoglobin for blood substitute |
FR2799466A1 (fr) * | 1999-10-11 | 2001-04-13 | Inst Nat Sante Rech Med | Transporteurs artificiels d'oxygene a base d'hemoglobine ou de myoglobine |
WO2002039979A1 (fr) * | 2000-11-17 | 2002-05-23 | Centre National De La Recherche Scientifique (C.N.R.S.) | Copolymere a structure sequencee compose d'un segment saccharidique lie a au moins un segment hydrophobe bioerodable, et particules correspondantes |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4001401A (en) * | 1975-02-02 | 1977-01-04 | Alza Corporation | Blood substitute and blood plasma expander comprising polyhemoglobin |
US5616311A (en) * | 1991-01-15 | 1997-04-01 | Hemosphere, Inc. | Non-crosslinked protein particles for therapeutic and diagnostic use |
US6096331A (en) * | 1993-02-22 | 2000-08-01 | Vivorx Pharmaceuticals, Inc. | Methods and compositions useful for administration of chemotherapeutic agents |
US6333051B1 (en) * | 1998-09-03 | 2001-12-25 | Supratek Pharma, Inc. | Nanogel networks and biological agent compositions thereof |
-
2002
- 2002-09-17 FR FR0211518A patent/FR2844512B1/fr not_active Expired - Fee Related
-
2003
- 2003-06-10 WO PCT/FR2003/001435 patent/WO2004026278A1/fr active Application Filing
- 2003-06-10 US US10/533,084 patent/US20060182807A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5670173A (en) * | 1992-09-14 | 1997-09-23 | Mcgill University | Biodegradable polymer membrane containing hemoglobin for blood substitute |
FR2799466A1 (fr) * | 1999-10-11 | 2001-04-13 | Inst Nat Sante Rech Med | Transporteurs artificiels d'oxygene a base d'hemoglobine ou de myoglobine |
WO2002039979A1 (fr) * | 2000-11-17 | 2002-05-23 | Centre National De La Recherche Scientifique (C.N.R.S.) | Copolymere a structure sequencee compose d'un segment saccharidique lie a au moins un segment hydrophobe bioerodable, et particules correspondantes |
Non-Patent Citations (2)
Title |
---|
"Communiqué de presse, Prix de la Valorisation de la Recherche", B. BOURDON ET B. DEBUIRE, 25 June 2002 (2002-06-25), XP002227660, Retrieved from the Internet <URL:http://www.u-psud.fr/evenement.nsf/ec00752c0a54c65bc1256be400362827/$FILE/_s8dnmqrbldpkn2tc241984srldhq62t3j41b62r3f40p30c1i_.pdf> [retrieved on 20030117] * |
"Les Lauréats du Prix de la Valorisation de la Recherche 2002", UNIVERSITÉ PARIS-SUD XI, 11 July 2002 (2002-07-11), XP002227661, Retrieved from the Internet <URL:http://www.u-psud.fr/evenement.nsf/_oea176tbcehgn8spee1p6iu1depgmoc1i5pk78rbc_!OpenPage> [retrieved on 20030117] * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2009034458A2 (fr) * | 2007-09-11 | 2009-03-19 | Universität Basel | Nanorécipients polymères perméables à l'oxygène utilisables en vue de l'encapsulation de composés sensibles |
WO2009034458A3 (fr) * | 2007-09-11 | 2009-05-22 | Univ Basel | Nanorécipients polymères perméables à l'oxygène utilisables en vue de l'encapsulation de composés sensibles |
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FR2844512B1 (fr) | 2005-06-24 |
US20060182807A1 (en) | 2006-08-17 |
FR2844512A1 (fr) | 2004-03-19 |
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