WO2004108796A1 - Polyaminoacides fonctionnalises par au moins un groupement hydrophobe et leurs applications notamment therapeutiques - Google Patents
Polyaminoacides fonctionnalises par au moins un groupement hydrophobe et leurs applications notamment therapeutiques Download PDFInfo
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- WO2004108796A1 WO2004108796A1 PCT/FR2004/050209 FR2004050209W WO2004108796A1 WO 2004108796 A1 WO2004108796 A1 WO 2004108796A1 FR 2004050209 W FR2004050209 W FR 2004050209W WO 2004108796 A1 WO2004108796 A1 WO 2004108796A1
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- alpha
- polyamino acid
- amino acid
- composition according
- aspartic
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- 0 BC(C[C@](C)C(C(C(C)(C)NC(**)C(C(C)(C)*)=O)=O)N(C(C)*)N)=O Chemical compound BC(C[C@](C)C(C(C(C)(C)NC(**)C(C(C)(C)*)=O)=O)N(C(C)*)N)=O 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/88—Polyamides
-
- 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
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/02—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
- C08G69/08—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids derived from amino-carboxylic acids
- C08G69/10—Alpha-amino-carboxylic acids
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/48—Polymers modified by chemical after-treatment
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/57—Compounds covalently linked to a(n inert) carrier molecule, e.g. conjugates, pro-fragrances
Definitions
- the present invention relates to new materials based on biodegradable polyamino acids, useful in particular for the vectorization of active principle (s) (PA).
- PA active principle
- the invention also relates to new pharmaceutical, cosmetic, dietetic or phytosanitary compositions based on these polyamino acids.
- These compositions can be of the type of those allowing vectorization of AP and preferably being in the form of emulsions, micelles, particles, gels, implants or films.
- the APs considered are, advantageously, biologically active compounds which can be administered to an animal or human organism by the oral, parenteral, nasal, vaginal, ocular, subcutaneous, intravenous, intramuscular, intradermal, intraperitoneal, intracerebral route, buccal, etc.
- the PAs more particularly but not limited to concerned by the invention are proteins, glycoproteins, peptides, polysaccharides, lipopolysaccharides, oligo or polynucleotides, and organic molecules. However, it can also be cosmetic or phytosanitary products, such as herbicides, insecticides, fungicides, etc.
- polymers of the polylactic, polylactic-glycolic, polyoxyethylene-oxypropylene, polya inoacid or even polysaccharide type.
- These polymers constitute raw materials making it possible to manufacture, for example, mass implants, microparticles, nanoparticles, vesicles, micelles or gels.
- these polymers must be suitable for the manufacture of such systems, they must also be biocompatible, non-toxic, non-immunogenic. economical and they must be easily eliminated from the body and / or biodegradable.
- biodegradation in the organism generates non-toxic products.
- US-B-4, 652,441 describes microcapsules of polylactide encapsulating the hormone LH-RH. These microcapsules are produced by preparing a water-in-oil-in-water emulsion and comprise an aqueous internal layer containing the hormone, a substance (gelatin) fixing the latter, an oily layer of polylactide, as well as an aqueous external layer (polyvinyl alcohol). The release of the AP can be done over a period of more than two weeks after subcutaneous injection.
- AMyoshi et al. (J. Controlled Release 1998, 54, 313-320) describe pullulans which are made hydrophobic by grafting cholesterol and which form nanoparticles in water. These nanoparticles capable of reversibly complexing with insulin form stable colloidal suspensions.
- US-B-4,888,398 describes polymers based on polyglutamate or polyaspartate, and optionally polyleucine, with pendant groups of the alkyloxycarbonylmethyl type, placed randomly on the polyamino acid chain.
- These polyamino acids grafted by lateral groups e.g. methoxycarbonylmethyl, can be used in the form of biodegradable implants containing a prolonged release AP.
- US-B-5,904,936 describes nanoparticles obtained from a polyleucine-polyglutamate block polymer, capable of forming stable colloidal suspensions and capable of spontaneously associating with biologically active proteins without denaturing them. The latter can then be released in vivo in a controlled manner, over a long period.
- US-B-5,449,513 describes amphiphilic block copolymers comprising a polyoxyethylene block and a polyamino acid block, for example poly (beta-benzyl-L-aspartate). These polyoxyethylene-polybenzylaspartate polymers form micelles which are capable of encapsulating active hydrophobic molecules such as radryamicin or indomethacin.
- Patent application WO-A-99/61512 describes polylysines and polyornithines functionalized by a hydrophobic group (palmitic acid linked to polylysine or ornithine) and a hydrophilic group (polyoxyethylene). These polymers, for example polylysine grafted with polyoxyethylene and palmitoyl chains form vesicles capable of encapsulating doxorubicin or DNA in the presence of cholesterol. These polylysine-based polymers are cationic in a physiological medium.
- Patent application WO-A-00/30618 describes block or random polymers poly (sodium glutamate) -poly (methyl, ethyl, hexa-decyl or dodecyl glutamate), capable to form stable colloidal suspensions capable of spontaneously associating with biologically active proteins without denaturing them. The latter can then be released in vivo in a controlled manner, over a long period.
- These amphiphilic copolyamino acids are modified by the presence of a hydrophobic alkyl side chain. These alkyl groups are grafted covalently onto the polymer via an ester function.
- These polymers are anionic in a physiological medium.
- French unpublished patent application FR N ° 02/07008 of 7/06/2002 describes a polyglutamate carrying grafts based on alpha-tocopherol linked to a spacer formed by one to four "amino acid" residues and for example a leucine residue.
- one of the essential objectives of the present invention is to provide a new family of anionic polymers at animal physiological pH, based on polyglutamate and polyaspartate, which represent an improvement over those described in patent application WO-A-00/30618, in particular in terms of stability and absorption capacity of a protein.
- Another essential objective of the present invention is that these polymers are suitable for being used for the vectorization of AP and make it possible to optimally satisfy all the specifications of the specifications, namely in particular: o capacity:
- the present invention which firstly relates to a polyamino acid comprising aspartic units and / or glutamic units, some of which carry at least one graft, characterized in that at at least one of these grafts: "is linked to an aspartic or glutamic unit of the main chain, via a spacer comprising one or more (oligo) amino acid (s), formed by one or more "amino acid” units chosen from “amino acid” units having an alpha alkyl or aryl group, preferably from the "amino acid” units included in the group comprising alanine, valine, leucine, isoleucine and phenylalanine,
- the inventors perfected the known polyamino acids by finding, surprisingly and unexpectedly, that the grafting onto these polyamino acids of grafts comprising hydrophobic groups derived from alcohol-type precursors are linked to the polymer via a spacer "(oligo) amino acid" having a substitution in the alpha position, the stability of the ester bond in aqueous medium is greatly improved.
- each graft is connected to an aspartic or glutamic unit of the main chain via an amide bond.
- polyamino acid covers both oligoamino acids comprising from 2 to 20 “amino acid” units and polyamino acids comprising more than 20 “amino acid” units.
- the oligoamino acid or the (oligo) amino acids of all or part of the grafts is (are) constituted (s) (each) by "amino acid" units identical to each other.
- association or "associate” used to qualify the relationships between one or more active ingredients and polyamino acids, mean in particular that the active ingredient (s) are linked to ( x) polyamino acid (s) in particular by a weak bond, for example by ionic bond and / or by hydrophobic contact, and / or are encapsulated by the polyamino acid (s).
- the polyamino acids according to the present invention are oligomers or homopolymers comprising repeating units of glutamic or aspartic acid or copolymers comprising a mixture of these two types of "amino acid” units.
- the units considered in these polymers are amino acids having the D or L or D / L configuration and are linked by their alpha or gamma positions for the glutamate or glutamic unit and alpha or beta for the aspartic or aspartate unit.
- the preferred "amino acid" units of the main polyamino acid chain are those having the L configuration and an alpha-type bond.
- polyamino acids according to the invention correspond to the following general formula (I):
- R 1 represents an H, a linear acyl group in C2 to C10 or branched in
- R 2 represents an H, a linear C2 to CIO or branched C3 to alkyl
- R 3 is an H or a canonical entity, preferably selected from the group comprising:
- - metal cations advantageously chosen from the subgroup comprising: sodium, potassium, calcium, magnesium;
- Cations based on arnine acid (s) advantageously chosen from the class comprising cations based on lysine or arginine,
- n groups B each independently represent a monovalent radical of the following formula:
- R represents methyl (alanine), isopropyl (valine), isobutyl (leucine), secbutyl (isoleucine), benzyl (phenylalanine), the amino acids mentioned in parentheses are those which correspond to the "amino acid" unit formed when R 4 represents the alkyl considered;
- R 5 represents a hydrophobic group comprising 6 to 30 (for example 8 to 30) carbon atoms and preferably bonded to the polymer (more precisely to the spacer [-NH-CHR4-CO-] 1 via an ester function;
- A independently represents a -CH 2 - (aspartic unit) or -CH 2 -CH 2 -
- n / (n + m) is defined as the molar grafting rate and varies from 0.5 to
- n + m varies from 3 to 1000, preferably between 30 and 300.
- all or part of the hydrophobic groups R 5 of the grafts are chosen independently from the group of radicals comprising:
- a linear or branched alkoxy comprising from 6 to 30 carbon atoms and which may comprise at least one heteroatom (preferably O and or N and / or S) and / or at least one unsaturation, • an alkoxy comprising 6 to 30 atoms carbon and having one or more ringed carbocycles and optionally containing at least one unsaturation and or at least one heteroatom (preferably O and or N and / or S), • an alkoxyaryl or an aryloxyalkyl of 7 to 30 carbon atoms and which may comprise at least one msaturation and / or at least one heteroatom (preferably O and / or N and / or S).
- the hydrophobic group of the graft is derived from an alcoholic precursor is chosen from the group comprising: Toctanol, dodecanol, tetradecanol, Phexadecanol, Foctadecanol, Foleylalcohol or cholesterol.
- amino acid unit of the graft a “amino acid” unit originating from the group comprising: L-leucine, L-valine or L-phenylalanine will more particularly be chosen within the framework of the invention. .
- the main chains of the polyamino acids are homopolymers of alpha-L-glutamate or of alpha-L-glutamic.
- the main chains of the polyamino acids are homopolymers of alpha-L-aspartate or of alpha-L-aspartic.
- the main chains of the polyamino acids are copolymers of alpha-L-aspartate / alpha-L-glutamate or of alpha-L-aspartic / alpha-L-glutamic acid.
- the distribution of the aspartic and / or glutamic units of the main polyamino acid chain is such that the polymers thus formed are either random, or of block type, or of multiblock type.
- the polyamino acids according to the invention have a molar mass which is between 2,000 and 100,000 g / mole, and preferably between 5,000 and 40,000 g / mole.
- the rate of molar grafting in hydrophobic unit of the polyamino acids according to the invention is between 2 and 70%, and preferably between 5 and 40%.
- the polyamino acids of the invention can be used in several ways depending on the grafting rate.
- Methods of forming a polymer for the encapsulation of an active principle in the various forms targeted by the invention are known to those skilled in the art. For more details, one can refer, for example to these some particularly relevant references:
- Polyamino acids are also extremely interesting, because at a relatively low grafting rate of the order of 3 to 30, they disperse in water at pH 7.4 (for example with a phosphate buffer) to give colloidal solutions or suspensions or gels, depending on the polymer concentration and the grafting rate.
- polyamino acids in the form of particles or not
- the preferred shaping is that described in patent application WO-A-00/30618 of the applicant and which consists in dispersing the polymer in water and in incubating the solution in the presence of an AP.
- This colloidal solution of vectoring particles consisting of the polyamino acids according to the invention can then be filtered under 0.2 ⁇ m and then directly injected into a patient.
- the polymer can then form microparticles capable of associating or encapsulating PAs.
- the microparticles can be shaped by co-solubilizing the PA and the polymer in an appropriate organic solvent and then the mixture precipitated in water.
- the particles are then recovered by filtration and can then be used for oral administration (in the form of a capsule, in compacted and / or coated form or alternatively in dispersed form in an oil) or parenterally after redispersion in the water.
- the redispersion of the polymer in the aqueous phase becomes more difficult due to the lower amount of the ionizable carboxylate functions and the polymer precipitates.
- the polymer can be dissolved in a biocompatible solvent such as N-methylpyrrolidone or an appropriate oil such as Mygliol® and then injected intramuscularly or subcutaneously or in a tumor. The diffusion of the solvent or oil leads to precipitation of the polymer at the injection site and thus forms a deposit. These deposits then provide controlled release by diffusion and or by erosion and or by hydrolytic or enzymatic degradation of the polymer.
- the polymers of the invention in neutral or ionized form, are more generally usable alone or in a liquid, solid or gel composition and in a medium. aqueous or organic.
- the polyamino acid-based polymer contains carboxyl groups which are either neutral (COOH form) or ionized (anion COO "), depending on pH and composition.
- the solubility in an aqueous phase is directly a function of the level of free COOH of the polymer (not grafted by the hydrophobic unit) and of the pH.
- the counter-cation can be a metal cation such as sodium, calcium or magnesium, or an organic cation such as triethanolamine, fried (hycuOxymémyl) -ammomethane or a polyamine such as polyethyleneimine.
- the polymers of the invention are for example obtained by methods known to those skilled in the art.
- the random polyamino acids can be obtained by grafting the hydrophobic graft, previously functionalized with the amino acid spacer, directly on the polymer by a conventional coupling reaction.
- the block or multi-block polyamino acids can be obtained by sequential polymerization of the corresponding N-carboxy-amino acid anhydrides (NCA).
- a polyamino acid, homopolyglutamate, homopolyaspartate or a glutamate / aspartate, block, multiblock or random copolymer is prepared according to conventional methods.
- N-carboxy-amino acid anhydrides NCA
- the polymers are then hydrolyzed under appropriate conditions to obtain the polymer in its acid form.
- polysuccirdmide polysuccirdmide
- basic hydrolysis cf. Tomida et al. Polymer 1997, 38, 4733-36
- the coupling of the graft with an acid function of the polymer is easily carried out by reaction of the polyamino acid in the presence of a carbodiimide as coupling agent and optionally, a catalyst such as 4-dimethylammopyridine and in an appropriate solvent such as dimethylformamide (DMF) , N-methyl pyrrolidone (NMP) or dimethylsulfoxide (DMSO).
- a carbodiimide is for example, dicyclohexylcarbodiimide or ⁇ isopropylcarbodiimide.
- the grafting rate is controlled chemically by the stoichiometry of the constituents and reagents or the reaction time. Hydrophobic grafts functionalized with an amino acid are obtained by conventional peptide coupling or by direct condensation by acid catalysis. These techniques are well known to those skilled in the art.
- the NCA-hydrophobic derivative is copolymerized with NCA-O-Benzyl and then the benzyl groups are removed by hydrolysis selectively.
- the invention relates to a pharmaceutical, cosmetic, dietetic or phytosanitary composition
- a pharmaceutical, cosmetic, dietetic or phytosanitary composition comprising at least one polyamino acid as defined above and optionally at least one active principle, which can be therapeutic, cosmetic, dietetic or phytosanitary.
- the active principle is associated with the polyamino acid (s) by one or more bonds other than (or only) covalent chemical bond (s) ).
- PNs • placing in aqueous solution of PA, then addition of the PNs, either in the form of a colloidal suspension, or in the form of isolated PNs (lyophilisate or precipitate);
- the active principle is a protein, a glycoprotein, a protein linked to one or more polyalkylene glycol chains (preferably Polyethylene glycol (PEG): "protein-PEGylated”), a polysaccharide, a liposaccharide, an oligonucleotide, a polynucleotide or a peptide.
- PEG Polyethylene glycol
- the active principle is a "small" hydrophobic, hydrophilic or amphiphilic organic molecule.
- a "small” molecule is in particular a small non-protein molecule.
- AP which can be associated with the polyamino acids according to the invention, whether or not in the form of (nano or micro) particles, mention may be made of: o proteins such as insulin, interferons, hormones growth, interleukins, erythropoietin or cytokines; o peptides such as leuprolide or cyclosporine; o small molecules such as those belonging to the family of anthracyclines, taxoids or camptothecins; o and their mixtures.
- the composition of the invention is in the form of a gel, a solution, a suspension, an emulsion, micelles, nanoparticles, microparticles, an implant, 'a powder or film.
- the composition, charged or not charged with active principle (s) is a stable colloidal suspension of nanoparticles and / or microparticles and / or micelles of polyamino acids, in an aqueous phase.
- the composition of the invention is in the form of a solution in a biocompatible solvent and can be injected subcutaneously, intramuscularly or into a tumor.
- composition according to the invention can be administered by the oral, parenteral, nasal, vaginal, ocular, subcutaneous, intravenous, intramuscular, intradermal, intraperitoneal, intracerebral or buccal route.
- composition is in the form of a solution in a biocompatible solvent, capable of being injected subcutaneously, intramuscularly or into a tumor.
- composition according to the invention is formulated such that it is capable of forming a deposit on the injection site.
- compositions which comprise polyamino acids according to the invention and active principles and which can be used for the preparation:
- drugs in particular for oral, nasal, vaginal, ocular, subcutaneous, intravenous, intramuscular, intradermal, intraperitoneal or intracerebral administration, the active principles of these drugs possibly being, in particular, proteins, glycoproteins, bound proteins with one or more polyalkylene glycol chains ⁇ for example Polyethylene glycol (PEG), we then speak of "PEGylated” proteins ⁇ , peptides, polysaccharides, liposaccharides, oligonucleotides, polynucleotides and small hydrophobic, hydrophilic or amphiphilic organic molecules;
- PEG Polyethylene glycol
- the invention relates to a preparation process: • drugs, in particular for oral, nasal, vaginal, ocular, subcutaneous, intravenous, intramuscular, intradermal, intraperitoneal or intracerebral administration, the active principles of these drugs possibly being, in particular, proteins, glycoproteins, bound proteins with one or more polyalkylene glycol chains ⁇ for example Polyethylene glycol (PEG), we then speak of "PEGylated” proteins ⁇ , peptides, polysaccharides, liposaccharides, oligonucleotides, polynucleotides and small hydrophobic, hydrophilic or amphiphilic organic molecules;
- drugs in particular for oral, nasal, vaginal, ocular, subcutaneous, intravenous, intramuscular, intradermal, intraperitoneal or intracerebral administration
- the active principles of these drugs possibly being, in particular, proteins, glycoproteins, bound proteins with one or more polyalkylene glycol chains ⁇ for example Polyethylene glycol (PEG), we then
- the invention also relates to a method of therapeutic treatment consisting essentially in administering the composition as described in the present description, by oral, parenteral, nasal, vaginal, ocular, subcutaneous, intravenous, intramuscular, intradermal, intraperitoneal, intracerebral or oral.
- this method of therapeutic treatment essentially consists in administering the composition as described above in the form of a solution in a biocompatible solvent and then injecting it subcutaneously, intramuscularly or into a tumor, preferably so that it forms a deposit at the injection site.
- This product is synthesized from L-leucine and dodecanol by condensation in the presence of an acid, according to a process described in patent US-A-4,826,818.
- the alpha-L-polyglutamic polymer (with a mass equivalent to approximately 12,000 g / mol relative to a polyoxyethylene standard) is obtained by polymerization of monomers constituted by N-Carboxy derivativesMethyl glutamate anhydride: NCAGluOMe. This polymerization is followed by hydrolysis as described in patent application FR-A-2 801 226. 18 g of the polymer is then dissolved in 360 ml of DMethylFormamide (DMF) while heating at 80 ° C for 2 hours. Once the polymer has dissolved, the temperature is allowed to return to 25 ° C.
- DMF DMethylFormamide
- the polymers P2 to P5 and the comparative examples C1 and C2 are synthesized according to the same protocol as for the polymer PI.
- For the NalChol graft we carried out a coupling of cholesterol with Bocvaline in the presence of diisopropylcarbodiimide monitoring of the deprotection of Tamine in an acid medium (see for example the work “Principles of peptide synthesis” by Bodanszky, Springer-Nerlag 1984).
- aqueous solution is prepared containing 10 mg of polymer per milliliter at pH 7.4 and 200 IU of insulin (7.4 mg). The solutions are incubated for two hours at room temperature and the free insulin is separated from the associated insulin by ultiafiltration (threshold at 100 KDa, 15 minutes under 10000G at 18 ° C). The free insulin recovered in the filtrate is then determined by HPLC (High Performance Liquid Chromatography) and the amount of associated insulin is deduced. The results are given in Table 2 below.
- Example 5 Study of the stability of polymers in an aqueous medium.
- the polymers are dissolved in 20 mg / ml of water by adjusting the pH to 6.0 and the clear solutions are then placed in temperature-controlled ovens at 25 or 37 ° C for one week.
- the pH range useful in the targeted applications is often between 6 and 7.4.
- Analysis of the polymers by various techniques shows that the only way of degradation of the polymer under these conditions is the hydrolysis of the ester grafts.
- the hydrolysis rate of polymers PI, P3 and Cl as a function of time is given in table 3 below. Table 3
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
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JP2006530446A JP4896723B2 (ja) | 2003-05-28 | 2004-05-28 | 少なくとも1つの疎水性基で官能化されたポリアミノ酸及びその応用、特に治療用応用 |
EP04742877A EP1633800B9 (fr) | 2003-05-28 | 2004-05-28 | Polyaminoacides fonctionnalises par au moins un groupement hydrophobe et leurs applications notamment therapeutiques |
CA002526435A CA2526435A1 (fr) | 2003-05-28 | 2004-05-28 | Polyaminoacides fonctionnalises par au moins un groupement hydrophobe et leurs applications notamment therapeutiques |
US10/558,617 US7919572B2 (en) | 2003-05-28 | 2004-05-28 | Polyamino acids functionalised with at least one hydrophobic group and applications thereof particularly therapeutic applications |
Applications Claiming Priority (2)
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FR0350190A FR2855521B1 (fr) | 2003-05-28 | 2003-05-28 | Polyaminoacides fonctionnalises par au moins un groupement h ydrophobe et leurs applications notamment therapeutiques. |
FR0350190 | 2003-05-28 |
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US (1) | US7919572B2 (fr) |
EP (1) | EP1633800B9 (fr) |
JP (1) | JP4896723B2 (fr) |
CA (1) | CA2526435A1 (fr) |
FR (1) | FR2855521B1 (fr) |
WO (1) | WO2004108796A1 (fr) |
Cited By (4)
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EP1773914B1 (fr) * | 2004-07-30 | 2009-11-25 | Flamel Technologies | Polyaminoacides fonctionnalises par des greffons hydrophobes portant une charge anionique et leurs applications notamment therapeutiques |
EP1689425B1 (fr) * | 2003-11-21 | 2009-12-09 | FLAMEL TECHNOLOGIE, Société Anonyme | Formulations pharmaceutiques pour la libération prolongée de principe(s) actif(s), ainsi que leurs applications notamment therapeutiques |
US7683024B2 (en) | 2002-06-07 | 2010-03-23 | Flamel Technologies | Polyaminoacids functionalized by alpha tocopherol and uses thereof, particular for therapeutic applications |
AU2004292370B2 (en) * | 2003-11-21 | 2010-12-02 | Flamel Technologies | Pharmaceutical formulations for the sustained release of interferons and therapeutic applications thereof |
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FR2843117B1 (fr) | 2002-07-30 | 2004-10-15 | Flamel Tech Sa | Polyaminoacides fonctionnalises par au moins un groupement hydrophobe et leurs applications notamment therapeutiques |
FR2860516B1 (fr) | 2003-10-03 | 2006-01-13 | Flamel Tech Sa | Homopolyaminoacides telecheliques fonctionnalises par des groupements hydrophobes et leurs applications notamment therapeutiques |
FR2862535B1 (fr) * | 2003-11-21 | 2007-11-23 | Flamel Tech Sa | Formulations pharmaceutiques pour la liberation prolongee d'interleukines et leurs applications therapeutiques |
FR2881140B1 (fr) * | 2005-01-27 | 2007-04-06 | Flamel Technologies Sa | Copolyhydroxyalkylglutamines fonctionnalises par des groupements hydrophobes et leurs applications notamment therapeutiques |
EP2206736B1 (fr) * | 2005-12-05 | 2012-02-08 | Nitto Denko Corporation | Conjugués d'acide polyglutamate-aminé et procédés |
PE20110235A1 (es) | 2006-05-04 | 2011-04-14 | Boehringer Ingelheim Int | Combinaciones farmaceuticas que comprenden linagliptina y metmorfina |
EP1852108A1 (fr) | 2006-05-04 | 2007-11-07 | Boehringer Ingelheim Pharma GmbH & Co.KG | Compositions d'inhibiteurs de la DPP IV |
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US20080181852A1 (en) * | 2007-01-29 | 2008-07-31 | Nitto Denko Corporation | Multi-functional Drug Carriers |
FR2915684B1 (fr) | 2007-05-03 | 2011-01-14 | Flamel Tech Sa | Particules a base de polyelectrolytes et de principe actif a liberation modifiee et formulations pharmaceutiques contenant ces particules |
FR2915683B1 (fr) * | 2007-05-03 | 2009-08-07 | Flamel Technologies Sa | Formulations pharmaceutiques auto-precipitantes pour la liberation modifiee de principe actif |
FR2915748B1 (fr) * | 2007-05-03 | 2012-10-19 | Flamel Tech Sa | Acides polyglutamiques fonctionnalises par des groupes cationiques et des groupements hydrophobes et leurs applications, notamment therapeutiques |
US8486467B1 (en) * | 2007-09-20 | 2013-07-16 | Albert G. Prescott | Dermal filler and method of using same |
PE20091730A1 (es) | 2008-04-03 | 2009-12-10 | Boehringer Ingelheim Int | Formulaciones que comprenden un inhibidor de dpp4 |
US20200155558A1 (en) | 2018-11-20 | 2020-05-21 | Boehringer Ingelheim International Gmbh | Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug |
FR2940619B1 (fr) | 2008-12-31 | 2012-02-10 | Flamel Technologies Sa | Composition comprenant un actif de solubilite aqueuse faible ou moyenne |
TWI448485B (zh) * | 2010-08-03 | 2014-08-11 | Univ Nat Taiwan Normal | 半互穿網絡型水膠聚合物、其製造方法及包含其之水泥組成物 |
US9034883B2 (en) | 2010-11-15 | 2015-05-19 | Boehringer Ingelheim International Gmbh | Vasoprotective and cardioprotective antidiabetic therapy |
EP3129425B1 (fr) * | 2014-04-07 | 2019-04-10 | Nitto Denko Corporation | Agents hydrotropes à base de polymère pour administration de médicaments hydrophobes |
FR3083088B1 (fr) * | 2018-06-29 | 2020-10-02 | Adocia | Solution injectable a ph 7 comprenant au moins une insuline basale dont le pi est compris entre 5,8 et 8,5 et un co-polyaminoacide porteur de charges carboxylates et de radicaux hydrophobes |
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WO2019110788A1 (fr) * | 2017-12-07 | 2019-06-13 | Adocia | Compositions sous forme d'une solution aqueuse injectable comprenant de l'amyline, un agoniste au recepteur de l'amyline ou un analogue d'amyline et un co-polyaminoacide |
CA3084688A1 (fr) | 2017-12-07 | 2019-06-13 | Adocia | Solution injectable a ph 7 comprenant au moins une insuline basale dont le pi est compris entre 5,8 et 8,5 et un co-polyaminoacide porteur de charges carboxylates et de radicaux hydrophobes |
FR3083085B1 (fr) * | 2018-06-29 | 2020-10-02 | Adocia | Compositions sous forme d'une solution aqueuse injectable comprenant de l'amyline, un agoniste au recepteur de l'amyline ou un analogue d'amyline et un co-polyaminoacide |
AU2018380901A1 (en) | 2017-12-07 | 2020-06-11 | Adocia | Compositions in the form of an injectable aqueous solution comprising amylin, an amylin receptor agonist or an amylin analog and a copolyamino acid |
CN111565710A (zh) | 2017-12-07 | 2020-08-21 | 阿道恰公司 | 包含胰淀素、胰淀素受体激动剂或胰淀素类似物以及共聚氨基酸的呈可注射水溶液形式的组合物 |
WO2019110773A1 (fr) * | 2017-12-07 | 2019-06-13 | Adocia | Solution injectable a ph 7 comprenant au moins une insuline basale dont le pi est compris entre 5,8 et 8,5 et un co-polyaminoacide porteur de charges carboxylates et de radicaux hydrophobes |
EP3774017B1 (fr) * | 2018-09-19 | 2022-06-15 | Firmenich SA | Procédé de préparation de microcapsules basées sur des dérivés de polysuccinimide |
EP4308288A1 (fr) * | 2021-03-18 | 2024-01-24 | Agfa-Gevaert Nv | Capsules à base de poly(acide aminé) |
Citations (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4351337A (en) | 1973-05-17 | 1982-09-28 | Arthur D. Little, Inc. | Biodegradable, implantable drug delivery device, and process for preparing and using the same |
EP0179023A2 (fr) * | 1984-10-19 | 1986-04-23 | Battelle Memorial Institute | Polypeptide biodégradable et son utilisation pour le relargage progressif de médicaments |
US4652441A (en) | 1983-11-04 | 1987-03-24 | Takeda Chemical Industries, Ltd. | Prolonged release microcapsule and its production |
WO1987003891A1 (fr) * | 1985-12-19 | 1987-07-02 | Battelle Memorial Institute | Polypeptide synthetique biodegradable et son utilisation en therapeutique |
US4826818A (en) | 1983-10-26 | 1989-05-02 | Kanebo Ltd. | Proteinaceous emulsifier, process for preparing same and emulsion type cosmetic compositions containing same |
US5449513A (en) | 1992-08-14 | 1995-09-12 | Research Development Corporation Of Japan | Physical trapping type polymeric micelle drug preparation |
WO1996029991A1 (fr) * | 1995-03-28 | 1996-10-03 | Flamel Technologies | Particules a base de polyaminoacide(s) et susceptibles d'etre utilisees comme vecteurs de principe(s) actif(s) et leurs procedes de preparation |
WO1999061512A1 (fr) | 1998-05-23 | 1999-12-02 | University Of Strathclyde | Vesicules formees a partir d'acide polyamine |
WO2000030618A1 (fr) | 1998-11-20 | 2000-06-02 | Flamel Technologies | Particules a base de polyaminoacide(s) et leurs procedes de fabrication |
US6153193A (en) | 1993-04-28 | 2000-11-28 | Supratek Pharma Inc. | Compositions for targeting biological agents |
WO2000078791A2 (fr) * | 1999-06-17 | 2000-12-28 | Universiteit Gent | DERIVES FONCTIONNELS POLY-α-AMINO ACIDE UTILES POUR LA MODIFICATION DE MATIERES A ACTIVITE BIOLOGIQUE ET APPLICATION DE CES DERIVES |
FR2801226A1 (fr) | 1999-11-23 | 2001-05-25 | Flamel Tech Sa | Suspension colloidale de particules submicroniques de vectorisation de principes actifs et son mode de preparation |
US20020169125A1 (en) * | 2001-03-21 | 2002-11-14 | Cell Therapeutics, Inc. | Recombinant production of polyanionic polymers and uses thereof |
Family Cites Families (64)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2680749A (en) * | 1951-12-01 | 1954-06-08 | Eastman Kodak Co | Water-soluble tocopherol derivatives |
US4126628A (en) * | 1977-03-28 | 1978-11-21 | Canadian Patents And Development Limited | Acylation of amino acids |
FR2533209B1 (fr) * | 1982-09-22 | 1985-11-08 | Centre Nat Rech Scient | Lipopeptides, leur obtention et leur application comme emulsifiants |
US4766106A (en) * | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
MX9203291A (es) * | 1985-06-26 | 1992-08-01 | Liposome Co Inc | Metodo para acoplamiento de liposomas. |
US5102872A (en) * | 1985-09-20 | 1992-04-07 | Cetus Corporation | Controlled-release formulations of interleukin-2 |
US4861580A (en) | 1985-10-15 | 1989-08-29 | The Liposome Company, Inc. | Composition using salt form of organic acid derivative of alpha-tocopheral |
CA1340681C (fr) * | 1989-07-07 | 1999-07-27 | Robert Deziel | Tetrapeptides antiherpetiques, a chaine laterale constituee d'acide aspartique avec substitution |
SE9002684D0 (sv) * | 1990-08-17 | 1990-08-17 | Malvac Foundation C O Peter Pe | New peptides and their use |
FR2686899B1 (fr) * | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
US5792451A (en) * | 1994-03-02 | 1998-08-11 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
DE4221875A1 (de) * | 1992-07-03 | 1994-01-05 | Basf Ag | Modifizierte Polyasparaginsäuren, Verfahren zu ihrer Herstellung und ihre Verwendung |
WO1994012158A1 (fr) * | 1992-12-02 | 1994-06-09 | Alkermes Controlled Therapeutics, Inc. | Microspheres contenant une hormone de croissance a liberation regulee |
FR2702373B1 (fr) * | 1993-03-08 | 1996-06-07 | Rhone Merieux | Emulsions vaccinales fluides eau-dans-l'huile contenant une huile métabolisable. |
IL109403A0 (en) * | 1993-04-22 | 1994-07-31 | Emisphere Tech Inc | Oral drug delivery compositions and methods |
EP0698040A4 (fr) * | 1993-05-20 | 1999-01-07 | Biotech Australia Pty Ltd | Antagonistes de la lhrh |
US5534241A (en) * | 1993-07-23 | 1996-07-09 | Torchilin; Vladimir P. | Amphipathic polychelating compounds and methods of use |
US5478919A (en) * | 1994-07-29 | 1995-12-26 | Donlar Corporation | Aspartic acid copolymers and their preparation |
US6001347A (en) * | 1995-03-31 | 1999-12-14 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
US5872210A (en) * | 1995-10-05 | 1999-02-16 | The United States Of America As Represented By The Department Of Health And Human Services | Transframe peptide inhibitor of viral protease |
DE19543161A1 (de) * | 1995-11-18 | 1997-05-22 | Basf Ag | Verfahren zur Herstellung von verzweigten Polyamiden |
JPH09165447A (ja) * | 1995-12-15 | 1997-06-24 | Mitsubishi Chem Corp | ポリアスパラギン酸共重合体及びその製造方法 |
FR2746035B1 (fr) * | 1996-03-15 | 1998-06-12 | Microparticules de gel composite susceptibles d'etre utilisees comme vecteur(s) de principe(s) actif(s), l'un de leurs procedes de preparation et leurs applications | |
US5929198A (en) * | 1996-07-16 | 1999-07-27 | Nalco Chemical Company | Biodegradable poly (amino acid)s, derivatized amino acid polymers and methods for making same |
US6284267B1 (en) * | 1996-08-14 | 2001-09-04 | Nutrimed Biotech | Amphiphilic materials and liposome formulations thereof |
SE9603480L (sv) | 1996-09-23 | 1998-03-24 | Johan Carlfors | Beredningsform för svårlösliga läkemedel |
FR2758565B1 (fr) * | 1997-01-22 | 1999-02-19 | Atochem Elf Sa | Melanges de polymere a blocs polyamides et de copolymeres a motifs vinylaromatiques et motifs anhydride |
US5981761A (en) * | 1997-03-27 | 1999-11-09 | Solutia Inc. | Crosslinked polyaspartate salts a process for their production |
KR100195291B1 (ko) * | 1997-07-12 | 1999-06-15 | 서경배 | 비이온성 비타민 |
JP4656725B2 (ja) | 1997-10-03 | 2011-03-23 | プロセリックス・ソルト・レイク・シティ,インコーポレーテッド | 逆熱的ゲル化特性を有する生分解性低分子量トリブロックポリ(ラクチド−co−グリコリド)−ポリエチレングリコールコポリマー |
US6201072B1 (en) * | 1997-10-03 | 2001-03-13 | Macromed, Inc. | Biodegradable low molecular weight triblock poly(lactide-co- glycolide) polyethylene glycol copolymers having reverse thermal gelation properties |
US6320017B1 (en) * | 1997-12-23 | 2001-11-20 | Inex Pharmaceuticals Corp. | Polyamide oligomers |
JP2002502616A (ja) * | 1998-02-10 | 2002-01-29 | ユニバーシティ・オブ・ユタ・リサーチ・ファウンデーション | イモガイγ−カルボキシラーゼを精製しアッセイする方法 |
DE19822600C2 (de) * | 1998-05-20 | 2003-08-21 | Goldschmidt Ag Th | Copolymere, hydrophob modifizierte Polyasparaginsäureester mit erhöhter Molekularmasse |
US7030155B2 (en) * | 1998-06-05 | 2006-04-18 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
JP2000054170A (ja) * | 1998-08-10 | 2000-02-22 | Nippon Shokubai Co Ltd | 金属腐食防止剤 |
CN1177809C (zh) * | 1998-08-12 | 2004-12-01 | 味之素株式会社 | 新型聚氨基酸衍生物 |
US6143314A (en) * | 1998-10-28 | 2000-11-07 | Atrix Laboratories, Inc. | Controlled release liquid delivery compositions with low initial drug burst |
US6355270B1 (en) * | 1999-01-11 | 2002-03-12 | The Regents Of The University Of California | Particles for oral delivery of peptides and proteins |
US20040121954A1 (en) * | 1999-04-13 | 2004-06-24 | Xu Wuhan Jingya | Poly(dipeptide) as a drug carrier |
EP1185301A1 (fr) | 1999-05-24 | 2002-03-13 | Sonus Pharmaceuticals, Inc. | Excipient en emulsion pour medicaments faiblement solubles |
MXPA02003719A (es) * | 1999-10-12 | 2002-08-30 | Cell Therapeutics Inc | Fabricacion de congujados de poliglutamato-agente terapeutico. |
FR2814952B1 (fr) * | 2000-10-06 | 2004-01-02 | Flamel Tech Sa | Suspension colloidale de particules submicromiques de vectorisation de principes actifs et leur mode de preparation |
US7713544B2 (en) * | 2000-07-28 | 2010-05-11 | Emory University | Biological component comprising artificial membrane |
US20060177416A1 (en) * | 2003-10-14 | 2006-08-10 | Medivas, Llc | Polymer particle delivery compositions and methods of use |
US6499183B1 (en) | 2000-09-29 | 2002-12-31 | Oreck Holdings, Llc | Low-profile and highly-maneuverable vacuum cleaner having a headlight, a sidelight, anti-ingestion bars, side brushes, a squeegee, and a scent cartridge |
US20030129223A1 (en) * | 2000-10-11 | 2003-07-10 | Targesome, Inc. | Targeted multivalent macromolecules |
DE10050137A1 (de) * | 2000-10-11 | 2002-04-18 | Bayer Ag | Stabilisierte Mono- und Polyasparaginsäureester |
US6545097B2 (en) * | 2000-12-12 | 2003-04-08 | Scimed Life Systems, Inc. | Drug delivery compositions and medical devices containing block copolymer |
JP4775985B2 (ja) | 2000-12-27 | 2011-09-21 | 三井化学株式会社 | 重合体及びその製造方法 |
JP4585114B2 (ja) | 2000-12-27 | 2010-11-24 | 三井化学株式会社 | 重合体及びその製造方法 |
CA2444383A1 (fr) * | 2001-04-26 | 2002-11-07 | Board Of Regents, The University Of Texas System | Compositions therapeutiques conjuguees agent/ligand, leur methodes de synthese et leur utilisation |
EP1392756B1 (fr) | 2001-06-01 | 2007-02-14 | Astellas Pharma Europe B.V. | Conjugues lipide-polymere |
CA2450949C (fr) | 2001-06-28 | 2009-04-28 | John Samuel | Procedes et compositions d'antibiotiques de la famille des polyenes a toxicite reduite |
JP2004537627A (ja) * | 2001-08-03 | 2004-12-16 | ザ プロクター アンド ギャンブル カンパニー | 洗剤組成物に使用するためのポリアスパルテート誘導体 |
DE10200075A1 (de) * | 2002-01-03 | 2003-07-17 | Goldschmidt Ag Th | Verfahren zur Herstellung von copolymeren hydrophob modifizierten Polyglutaminsäurederivaten und ihre Verwendung |
MXPA04010989A (es) * | 2002-05-07 | 2005-07-14 | Aquero Company Llc | Copolimeros de aminoacidos y metodos de producirlos. |
JP2003327693A (ja) * | 2002-05-15 | 2003-11-19 | Mitsuru Akashi | 親−疎水性修飾ポリ(γ−グルタミン酸) |
FR2840614B1 (fr) * | 2002-06-07 | 2004-08-27 | Flamel Tech Sa | Polyaminoacides fonctionnalises par de l'alpha-tocopherol et leurs applications notamment therapeutiques |
US7033602B1 (en) * | 2002-06-21 | 2006-04-25 | Advanced Cardiovascular Systems, Inc. | Polycationic peptide coatings and methods of coating implantable medical devices |
FR2843117B1 (fr) * | 2002-07-30 | 2004-10-15 | Flamel Tech Sa | Polyaminoacides fonctionnalises par au moins un groupement hydrophobe et leurs applications notamment therapeutiques |
US6774207B2 (en) * | 2002-09-26 | 2004-08-10 | Bayer Polymers Llc | Polyaspartate resins with good hardness and flexibility |
EP1567578B1 (fr) * | 2002-12-04 | 2008-06-25 | Flamel Technologies | Polyaminoacides fonctionnalises par au moins un groupement (oligo)aminoacide et leurs applications notamment therapeutiques |
US6790925B2 (en) * | 2002-12-05 | 2004-09-14 | Bayer Polymers Llc | In-situ preparation of polyaspartic ester mixtures |
-
2003
- 2003-05-28 FR FR0350190A patent/FR2855521B1/fr not_active Expired - Fee Related
-
2004
- 2004-05-28 CA CA002526435A patent/CA2526435A1/fr not_active Abandoned
- 2004-05-28 WO PCT/FR2004/050209 patent/WO2004108796A1/fr active Application Filing
- 2004-05-28 US US10/558,617 patent/US7919572B2/en not_active Expired - Fee Related
- 2004-05-28 JP JP2006530446A patent/JP4896723B2/ja not_active Expired - Fee Related
- 2004-05-28 EP EP04742877A patent/EP1633800B9/fr not_active Expired - Fee Related
Patent Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4351337A (en) | 1973-05-17 | 1982-09-28 | Arthur D. Little, Inc. | Biodegradable, implantable drug delivery device, and process for preparing and using the same |
US4826818A (en) | 1983-10-26 | 1989-05-02 | Kanebo Ltd. | Proteinaceous emulsifier, process for preparing same and emulsion type cosmetic compositions containing same |
US4652441A (en) | 1983-11-04 | 1987-03-24 | Takeda Chemical Industries, Ltd. | Prolonged release microcapsule and its production |
EP0179023A2 (fr) * | 1984-10-19 | 1986-04-23 | Battelle Memorial Institute | Polypeptide biodégradable et son utilisation pour le relargage progressif de médicaments |
US4888398A (en) | 1984-10-19 | 1989-12-19 | Battelle Memorial Institute | Biodegradable polypeptide and the use thereof for the gradual release of drugs |
WO1987003891A1 (fr) * | 1985-12-19 | 1987-07-02 | Battelle Memorial Institute | Polypeptide synthetique biodegradable et son utilisation en therapeutique |
US5449513A (en) | 1992-08-14 | 1995-09-12 | Research Development Corporation Of Japan | Physical trapping type polymeric micelle drug preparation |
US6153193A (en) | 1993-04-28 | 2000-11-28 | Supratek Pharma Inc. | Compositions for targeting biological agents |
WO1996029991A1 (fr) * | 1995-03-28 | 1996-10-03 | Flamel Technologies | Particules a base de polyaminoacide(s) et susceptibles d'etre utilisees comme vecteurs de principe(s) actif(s) et leurs procedes de preparation |
US5904936A (en) | 1995-03-28 | 1999-05-18 | Flamel Technologies | Particles based on polyamino acid(s) and capable of being used as delivery vehicles for active principle(s) and method for preparing them |
WO1999061512A1 (fr) | 1998-05-23 | 1999-12-02 | University Of Strathclyde | Vesicules formees a partir d'acide polyamine |
WO2000030618A1 (fr) | 1998-11-20 | 2000-06-02 | Flamel Technologies | Particules a base de polyaminoacide(s) et leurs procedes de fabrication |
WO2000078791A2 (fr) * | 1999-06-17 | 2000-12-28 | Universiteit Gent | DERIVES FONCTIONNELS POLY-α-AMINO ACIDE UTILES POUR LA MODIFICATION DE MATIERES A ACTIVITE BIOLOGIQUE ET APPLICATION DE CES DERIVES |
FR2801226A1 (fr) | 1999-11-23 | 2001-05-25 | Flamel Tech Sa | Suspension colloidale de particules submicroniques de vectorisation de principes actifs et son mode de preparation |
US20020169125A1 (en) * | 2001-03-21 | 2002-11-14 | Cell Therapeutics, Inc. | Recombinant production of polyanionic polymers and uses thereof |
Non-Patent Citations (7)
Title |
---|
"Biopolymers", vol. 15, 1976, SPRINGER VERLAG, article "alpha-Aminoacid-N-carboxy Anhydride and related Heterocycles", pages: 1869 |
"Colloidal Drug Delivery Systems", 1994, MARCEL DEKKER, INE. |
"Handbook of Phannaceutical Controlled Release Technology", 2000, MARCEL DEKKER, INE. |
"Préparation and chemical applications", vol. 1, 1999, CITUS BOOKS, article "Microspheres, Microcapsules and Liposomes" |
"Sustained-Release Injectable Products", 2000, INTERPHARM PRESS |
AKIYOSHI ET AL., J. CONTROLLED RELEASE, vol. 54, 1998, pages 313 - 320 |
BODANSZKY: "Principles of peptide synthesis", 1984, SPRINGER-VERLAG |
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US7683024B2 (en) | 2002-06-07 | 2010-03-23 | Flamel Technologies | Polyaminoacids functionalized by alpha tocopherol and uses thereof, particular for therapeutic applications |
EP1689425B1 (fr) * | 2003-11-21 | 2009-12-09 | FLAMEL TECHNOLOGIE, Société Anonyme | Formulations pharmaceutiques pour la libération prolongée de principe(s) actif(s), ainsi que leurs applications notamment therapeutiques |
AU2004292370B2 (en) * | 2003-11-21 | 2010-12-02 | Flamel Technologies | Pharmaceutical formulations for the sustained release of interferons and therapeutic applications thereof |
AU2004292369B2 (en) * | 2003-11-21 | 2010-12-09 | Flamel Ireland Limited | Pharmaceutical formulations for the sustained release of one or more active principles and applications thereof, such as therapeutic applications |
EP1773914B1 (fr) * | 2004-07-30 | 2009-11-25 | Flamel Technologies | Polyaminoacides fonctionnalises par des greffons hydrophobes portant une charge anionique et leurs applications notamment therapeutiques |
Also Published As
Publication number | Publication date |
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JP4896723B2 (ja) | 2012-03-14 |
JP2007501321A (ja) | 2007-01-25 |
EP1633800B9 (fr) | 2012-02-29 |
FR2855521B1 (fr) | 2005-08-05 |
EP1633800A1 (fr) | 2006-03-15 |
FR2855521A1 (fr) | 2004-12-03 |
EP1633800B1 (fr) | 2011-08-10 |
US20070010652A1 (en) | 2007-01-11 |
US7919572B2 (en) | 2011-04-05 |
CA2526435A1 (fr) | 2004-12-16 |
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