RU2006142100A - Пэг-илированные наночастицы - Google Patents
Пэг-илированные наночастицы Download PDFInfo
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- RU2006142100A RU2006142100A RU2006142100/15A RU2006142100A RU2006142100A RU 2006142100 A RU2006142100 A RU 2006142100A RU 2006142100/15 A RU2006142100/15 A RU 2006142100/15A RU 2006142100 A RU2006142100 A RU 2006142100A RU 2006142100 A RU2006142100 A RU 2006142100A
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- Prior art keywords
- polyethylene glycol
- nanoparticles according
- nanoparticles
- glycol
- active molecule
- Prior art date
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- 239000002105 nanoparticle Substances 0.000 title claims abstract 29
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract 21
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract 19
- 229920002988 biodegradable polymer Polymers 0.000 claims abstract 8
- 239000004621 biodegradable polymer Substances 0.000 claims abstract 8
- 229920001577 copolymer Polymers 0.000 claims abstract 5
- -1 2 -aminopropyl Chemical group 0.000 claims abstract 4
- 239000000203 mixture Substances 0.000 claims abstract 4
- 229920001451 polypropylene glycol Polymers 0.000 claims abstract 4
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 claims abstract 3
- XJRBAMWJDBPFIM-UHFFFAOYSA-N methyl vinyl ether Chemical compound COC=C XJRBAMWJDBPFIM-UHFFFAOYSA-N 0.000 claims abstract 3
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims abstract 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims abstract 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims abstract 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims abstract 2
- 229910019142 PO4 Inorganic materials 0.000 claims abstract 2
- 239000004698 Polyethylene Substances 0.000 claims abstract 2
- 239000004743 Polypropylene Substances 0.000 claims abstract 2
- 125000003545 alkoxy group Chemical group 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract 2
- 229920001400 block copolymer Polymers 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 2
- 150000002540 isothiocyanates Chemical class 0.000 claims abstract 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims abstract 2
- 239000010452 phosphate Substances 0.000 claims abstract 2
- 229920001515 polyalkylene glycol Polymers 0.000 claims abstract 2
- 229920000573 polyethylene Polymers 0.000 claims abstract 2
- 229920001155 polypropylene Polymers 0.000 claims abstract 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 2
- 108090000623 proteins and genes Proteins 0.000 claims abstract 2
- 102000004169 proteins and genes Human genes 0.000 claims abstract 2
- 229920005604 random copolymer Polymers 0.000 claims abstract 2
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims abstract 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims abstract 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims 8
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 239000003960 organic solvent Substances 0.000 claims 3
- 229920000642 polymer Polymers 0.000 claims 3
- 239000000427 antigen Substances 0.000 claims 2
- 102000036639 antigens Human genes 0.000 claims 2
- 108091007433 antigens Proteins 0.000 claims 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims 1
- 229930195725 Mannitol Natural products 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 108091034117 Oligonucleotide Proteins 0.000 claims 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims 1
- 229930006000 Sucrose Natural products 0.000 claims 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims 1
- 239000002671 adjuvant Substances 0.000 claims 1
- 239000013566 allergen Substances 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 239000007900 aqueous suspension Substances 0.000 claims 1
- 210000003169 central nervous system Anatomy 0.000 claims 1
- 239000002577 cryoprotective agent Substances 0.000 claims 1
- 238000004108 freeze drying Methods 0.000 claims 1
- 239000003862 glucocorticoid Substances 0.000 claims 1
- 238000009169 immunotherapy Methods 0.000 claims 1
- 238000011534 incubation Methods 0.000 claims 1
- 239000000594 mannitol Substances 0.000 claims 1
- 235000010355 mannitol Nutrition 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 210000004400 mucous membrane Anatomy 0.000 claims 1
- 239000002777 nucleoside Substances 0.000 claims 1
- 125000003835 nucleoside group Chemical group 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 239000012074 organic phase Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000012071 phase Substances 0.000 claims 1
- 108091033319 polynucleotide Proteins 0.000 claims 1
- 239000002157 polynucleotide Substances 0.000 claims 1
- 102000040430 polynucleotide Human genes 0.000 claims 1
- 239000003223 protective agent Substances 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 239000005720 sucrose Substances 0.000 claims 1
- 238000002255 vaccination Methods 0.000 claims 1
Classifications
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
-
- 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
- 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
- A61K47/6933—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 by reactions only involving carbon to carbon, e.g. poly(meth)acrylate, polystyrene, polyvinylpyrrolidone or polyvinylalcohol
-
- 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
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- 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
- A61K9/5192—Processes
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F222/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a carboxyl radical and containing at least one other carboxyl radical in the molecule; Salts, anhydrides, esters, amides, imides, or nitriles thereof
- C08F222/04—Anhydrides, e.g. cyclic anhydrides
- C08F222/06—Maleic anhydride
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S977/00—Nanotechnology
- Y10S977/70—Nanostructure
- Y10S977/773—Nanoparticle, i.e. structure having three dimensions of 100 nm or less
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nanotechnology (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Immunology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Biological Depolymerization Polymers (AREA)
Abstract
1. ПЭГ-илированные наночастицы для переноса биологически активных молекул, включающие биологически разлагаемый полимер и полиэтиленгликоль или его производные.2. Наночастицы по п. 1, отличающиеся тем, что биологически разлагаемый полимер представляет собой сополимер простого винилметилового эфира и малеинового ангидрида (PVM/MA).3. Наночастицы по п. 2, где сополимер имеет молекулярную массу в диапазоне от 100 до 2400 кДа, предпочтительнее от 200 до 2000 кДа, особенно предпочтительно от 180 до 250 кДа.4. Наночастицы по п.1, где полиэтиленгликоль или его производные имеют молекулярную массу от 400 до 35000 Да.5. Наночастицы по п.4, где полиэтиленгликоль выбран из группы полиэтиленгликолей, полипропиленгликолей, блок- или статистических сополимеров, включая 2 типа блоков, их смеси или их производные.6. Наночастицы по п.5, где полиэтиленгликоль имеет, по меньшей мере, одну модифицированную концевую гидроксильную группу, предпочтительно с алкокси-, акрилатной, метакрилатной, алкильной, амино-, фосфатной, изотиоцианатной, сульфгидрильной, меркапто- или сульфатной группой.7. Наночастицы по любому из пп.1-6, где полиалкиленгликоль выбран из группы, образованной полиэтиленгликолем 2000, простым метиловым эфиром полиэтиленгликоля 2000, O,O'-бис-(2-аминоэтил)полиэтиленгликоля 2000, O,O'-бис-(2-аминопропил)полипропиленгликоль-полиэтиленгликоль-полипропиленгликоля 2000 или их смесей.8. Наночастицы по п.1, где отношение массы полиэтиленгликоля к биологически разлагаемому полимеру составляет 1:2-6, предпочтительно 1:2-4, предпочтительнее примерно 1:4.9. Наночастицы по п.1, включающие белок или пептид в качестве активной молекулы.10. Наночастицы по п.1, включающие соедине
Claims (27)
1. ПЭГ-илированные наночастицы для переноса биологически активных молекул, включающие биологически разлагаемый полимер и полиэтиленгликоль или его производные.
2. Наночастицы по п. 1, отличающиеся тем, что биологически разлагаемый полимер представляет собой сополимер простого винилметилового эфира и малеинового ангидрида (PVM/MA).
3. Наночастицы по п. 2, где сополимер имеет молекулярную массу в диапазоне от 100 до 2400 кДа, предпочтительнее от 200 до 2000 кДа, особенно предпочтительно от 180 до 250 кДа.
4. Наночастицы по п.1, где полиэтиленгликоль или его производные имеют молекулярную массу от 400 до 35000 Да.
5. Наночастицы по п.4, где полиэтиленгликоль выбран из группы полиэтиленгликолей, полипропиленгликолей, блок- или статистических сополимеров, включая 2 типа блоков, их смеси или их производные.
6. Наночастицы по п.5, где полиэтиленгликоль имеет, по меньшей мере, одну модифицированную концевую гидроксильную группу, предпочтительно с алкокси-, акрилатной, метакрилатной, алкильной, амино-, фосфатной, изотиоцианатной, сульфгидрильной, меркапто- или сульфатной группой.
7. Наночастицы по любому из пп.1-6, где полиалкиленгликоль выбран из группы, образованной полиэтиленгликолем 2000, простым метиловым эфиром полиэтиленгликоля 2000, O,O'-бис-(2-аминоэтил)полиэтиленгликоля 2000, O,O'-бис-(2-аминопропил)полипропиленгликоль-полиэтиленгликоль-полипропиленгликоля 2000 или их смесей.
8. Наночастицы по п.1, где отношение массы полиэтиленгликоля к биологически разлагаемому полимеру составляет 1:2-6, предпочтительно 1:2-4, предпочтительнее примерно 1:4.
9. Наночастицы по п.1, включающие белок или пептид в качестве активной молекулы.
10. Наночастицы по п.1, включающие соединение, выбранное из группы, образованной ДНК, РНК, нуклеозидами, нуклеотидами, олигонуклеотидами или полинуклеотидами в качестве активной молекулы.
11. Наночастицы по п.1, включающие противоопухолевое средство или антиген для опухолей в качестве активной молекулы.
12. Наночастицы по п.1, включающие защитное средство центральной нервной системы или глюкокортикоид в качестве активной молекулы.
13. Наночастицы по п.1, включающие антиген для вакцинации или аллерген для иммунотерапии в качестве активной молекулы.
14. Фармацевтическая композиция, включающая ПЭГ-илированные наночастицы по любому из пп. 1-13, вместе с эксципиентом, носителем или адъювантом.
15. Фармацевтическая композиция по п. 14 для введения путем обеспечения доступа к слизистой оболочке организма, предпочтительно орально, ректально, интраназально, вагинально или интраокулярно.
16. Фармацевтическая композиция по п. 15 для орального введения.
17. Фармацевтическая композиция по п. 15 для глазного введения.
18. Применение наночастиц по любому из пп.1-13 при изготовлении лекарственного средства.
19. Лиофилизат, включающий ПЭГ-илированные наночастицы по любому из пп. 1-13.
20. Способ получения описанных ПЭГ-илированных наночастиц по любому из пп.1-13, включающий стадию одновременной инкубации полимера и полиэтиленгликоля в органическом растворителе перед десольватацией полимера водно-спиртовым раствором.
21. Способ по п. 20, отличающийся тем, что концентрация биологически разлагаемого полимера составляет от 0,001 до 10 мас.%/об., а концентрация полиэтиленгликоля - от 0,001 до 5 мас.%/об.
22. Способ по любому из пп. 20 или 21, отличающийся тем, что отношение органической фазы к фазе водно-спиртового раствора составляет от 1/1 до 1/10.
23. Способ по п. 20, отличающийся тем, что он включает дополнительные стадии для удаления органических растворителей и/или очистки.
24. Способ по п. 20, отличающийся тем, что активная молекула добавляется на стадии одновременной инкубации полимера и полиэтиленгликоля в органическом растворителе.
25. Способ по п. 20, отличающийся тем, что активная молекула добавляется к водной суспензии уже сформированных наночастиц.
26. Способ по п. 20, отличающийся тем, что включает дополнительную стадию лиофилизиации, необязательно в присутствии криопротективного средства, предпочтительно сахарозы или маннита.
27. Способ по п. 21, где биологически разлагаемый полимер представляет собой сополимер простого винилметилового эфира и малеинового ангидрида (PVM/MA), предпочтительно с молекулярной массой в диапазоне от 100 до 2400 кДа.
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EP1752142B1 (en) | 2009-09-16 |
CA2564982A1 (en) | 2005-11-10 |
RU2400215C2 (ru) | 2010-09-27 |
MXPA06012583A (es) | 2007-03-21 |
AU2005237270B2 (en) | 2011-02-17 |
ATE442841T1 (de) | 2009-10-15 |
CN1976688A (zh) | 2007-06-06 |
WO2005104648A2 (es) | 2005-11-10 |
BRPI0509827B1 (pt) | 2020-11-03 |
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