EA022803B1 - ПОЛИМЕРНЫЕ КОНЪЮГАТЫ ПАКЛИТАКСЕЛЯ И ДОЦЕТАКСЕЛЯ С КОНТРОЛИРУЕМЫМ ПОД ДЕЙСТВИЕМ pH ВЫСВОБОЖДЕНИЕМ КАНЦЕРОСТАТИЧЕСКОГО АГЕНТА - Google Patents
ПОЛИМЕРНЫЕ КОНЪЮГАТЫ ПАКЛИТАКСЕЛЯ И ДОЦЕТАКСЕЛЯ С КОНТРОЛИРУЕМЫМ ПОД ДЕЙСТВИЕМ pH ВЫСВОБОЖДЕНИЕМ КАНЦЕРОСТАТИЧЕСКОГО АГЕНТА Download PDFInfo
- Publication number
- EA022803B1 EA022803B1 EA201190315A EA201190315A EA022803B1 EA 022803 B1 EA022803 B1 EA 022803B1 EA 201190315 A EA201190315 A EA 201190315A EA 201190315 A EA201190315 A EA 201190315A EA 022803 B1 EA022803 B1 EA 022803B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- polymer
- drug
- ptx
- polymeric
- paclitaxel
- Prior art date
Links
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 title claims abstract description 72
- 229930012538 Paclitaxel Natural products 0.000 title claims abstract description 65
- 229960001592 paclitaxel Drugs 0.000 title claims abstract description 65
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 title claims abstract description 23
- 229960003668 docetaxel Drugs 0.000 title claims abstract description 22
- 230000003327 cancerostatic effect Effects 0.000 title description 7
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 45
- 229920001577 copolymer Polymers 0.000 claims abstract description 24
- 238000000034 method Methods 0.000 claims abstract description 16
- 102000015636 Oligopeptides Human genes 0.000 claims abstract description 12
- 108010038807 Oligopeptides Proteins 0.000 claims abstract description 12
- 239000000824 cytostatic agent Substances 0.000 claims abstract description 11
- VHSHLMUCYSAUQU-UHFFFAOYSA-N 2-hydroxypropyl methacrylate Chemical compound CC(O)COC(=O)C(C)=C VHSHLMUCYSAUQU-UHFFFAOYSA-N 0.000 claims abstract description 10
- OKPYIWASQZGASP-UHFFFAOYSA-N n-(2-hydroxypropyl)-2-methylprop-2-enamide Chemical compound CC(O)CNC(=O)C(C)=C OKPYIWASQZGASP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 150000001413 amino acids Chemical class 0.000 claims abstract description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 8
- 229940123237 Taxane Drugs 0.000 claims abstract description 7
- 150000004715 keto acids Chemical class 0.000 claims abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 3
- 150000007857 hydrazones Chemical class 0.000 claims abstract description 3
- 230000009466 transformation Effects 0.000 claims abstract description 3
- 229920000642 polymer Polymers 0.000 claims description 66
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 claims description 30
- -1 glycylglycilyl Chemical group 0.000 claims description 21
- 229940040102 levulinic acid Drugs 0.000 claims description 15
- 206010025323 Lymphomas Diseases 0.000 claims description 12
- FLZUYXUBDVKWPO-UHFFFAOYSA-N 4-(2-oxopropyl)benzoic acid Chemical compound CC(=O)CC1=CC=C(C(O)=O)C=C1 FLZUYXUBDVKWPO-UHFFFAOYSA-N 0.000 claims description 9
- 229920000578 graft copolymer Polymers 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 201000008275 breast carcinoma Diseases 0.000 claims description 5
- 125000000524 functional group Chemical group 0.000 claims description 5
- DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims description 3
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 210000000481 breast Anatomy 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 210000004072 lung Anatomy 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 229940126601 medicinal product Drugs 0.000 claims 1
- 230000001613 neoplastic effect Effects 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 75
- 229950005692 larotaxel Drugs 0.000 abstract description 7
- SEFGUGYLLVNFIJ-QDRLFVHASA-N larotaxel dihydrate Chemical compound O.O.O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@@]23[C@H]1[C@@]1(CO[C@@H]1C[C@@H]2C3)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 SEFGUGYLLVNFIJ-QDRLFVHASA-N 0.000 abstract description 7
- 150000002148 esters Chemical class 0.000 abstract description 6
- 238000002360 preparation method Methods 0.000 abstract description 6
- 229940079593 drug Drugs 0.000 description 70
- 241000699670 Mus sp. Species 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- 230000000694 effects Effects 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000003118 drug derivative Substances 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 12
- 238000006460 hydrolysis reaction Methods 0.000 description 11
- 125000006850 spacer group Chemical group 0.000 description 11
- 210000004881 tumor cell Anatomy 0.000 description 11
- 230000001093 anti-cancer Effects 0.000 description 10
- 239000002243 precursor Substances 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 238000002054 transplantation Methods 0.000 description 5
- 230000032258 transport Effects 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 238000009739 binding Methods 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 230000004087 circulation Effects 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000000178 monomer Substances 0.000 description 4
- 239000008363 phosphate buffer Substances 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000007334 copolymerization reaction Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 125000005597 hydrazone group Chemical group 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 230000004580 weight loss Effects 0.000 description 3
- XQAHOFAHGMZYNU-UHFFFAOYSA-N 5-oxohex-2-enoic acid Chemical compound CC(=O)CC=CC(O)=O XQAHOFAHGMZYNU-UHFFFAOYSA-N 0.000 description 2
- 102000013392 Carboxylesterase Human genes 0.000 description 2
- 108010051152 Carboxylesterase Proteins 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 206010042971 T-cell lymphoma Diseases 0.000 description 2
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 2
- 206010070863 Toxicity to various agents Diseases 0.000 description 2
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000007073 chemical hydrolysis Effects 0.000 description 2
- 230000001268 conjugating effect Effects 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229940058352 levulinate Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920002643 polyglutamic acid Polymers 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- XGTKSWVCNVUVHG-UHFFFAOYSA-N 4-oxopent-2-enoic acid Chemical compound CC(=O)C=CC(O)=O XGTKSWVCNVUVHG-UHFFFAOYSA-N 0.000 description 1
- JOOXCMJARBKPKM-UHFFFAOYSA-M 4-oxopentanoate Chemical compound CC(=O)CCC([O-])=O JOOXCMJARBKPKM-UHFFFAOYSA-M 0.000 description 1
- SPBQWHPKNVUQLO-UHFFFAOYSA-N 6-oxohept-2-enoic acid Chemical compound CC(=O)CCC=CC(O)=O SPBQWHPKNVUQLO-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 206010024264 Lethargy Diseases 0.000 description 1
- 241001409001 Maera Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 101150062708 Uso1 gene Proteins 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000002523 gelfiltration Methods 0.000 description 1
- 230000024924 glomerular filtration Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 150000004722 levulinic acids Chemical class 0.000 description 1
- 229920005684 linear copolymer Polymers 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- LYUQWAGPWZUFNV-UHFFFAOYSA-N n-(6-hydrazinyl-6-oxohexyl)-2-methylprop-2-enamide Chemical compound CC(=C)C(=O)NCCCCCC(=O)NN LYUQWAGPWZUFNV-UHFFFAOYSA-N 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 230000008884 pinocytosis Effects 0.000 description 1
- 229920001562 poly(N-(2-hydroxypropyl)methacrylamide) Polymers 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229920005604 random copolymer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 150000004579 taxol derivatives Chemical class 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Classifications
-
- 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
- A61K47/56—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—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 an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
-
- 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
- A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CZ20090085A CZ303072B6 (cs) | 2009-02-13 | 2009-02-13 | Polymerní konjugáty paclitaxelu a docetaxelu s pH rízeným uvolnováním kancerostatika |
| PCT/CZ2010/000014 WO2010091650A1 (en) | 2009-02-13 | 2010-02-09 | Polymeric conjugates of paclitaxel and docetaxel with ph-controlled releasing of the cancerostatic agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201190315A1 EA201190315A1 (ru) | 2012-05-30 |
| EA022803B1 true EA022803B1 (ru) | 2016-03-31 |
Family
ID=42309667
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201190315A EA022803B1 (ru) | 2009-02-13 | 2010-02-09 | ПОЛИМЕРНЫЕ КОНЪЮГАТЫ ПАКЛИТАКСЕЛЯ И ДОЦЕТАКСЕЛЯ С КОНТРОЛИРУЕМЫМ ПОД ДЕЙСТВИЕМ pH ВЫСВОБОЖДЕНИЕМ КАНЦЕРОСТАТИЧЕСКОГО АГЕНТА |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP2413973A1 (cs) |
| CZ (1) | CZ303072B6 (cs) |
| EA (1) | EA022803B1 (cs) |
| UA (1) | UA104187C2 (cs) |
| WO (1) | WO2010091650A1 (cs) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011147330A1 (zh) | 2010-05-27 | 2011-12-01 | 中国医学科学院药物研究所 | 双功能共缀物的化学合成及抗肿瘤与抗肿瘤转移作用 |
| US10500285B2 (en) | 2015-05-15 | 2019-12-10 | Zhuhai Beihai Biotech Co., Ltd. | Docetaxel and human serum albumin complexes |
| GB2551979A (en) * | 2016-06-30 | 2018-01-10 | Rs Arastirma Egitim Danismanlik Llac Sanayi Ticaret Ltd | Cleavable polymer drug conjugates |
| CN115487312B (zh) | 2016-10-27 | 2025-02-07 | 珠海贝海生物技术有限公司 | 多西他赛和人血清白蛋白的中性pH组合物 |
| CN118903095A (zh) | 2020-02-04 | 2024-11-08 | 珠海贝海生物技术有限公司 | 多西他赛制剂 |
| RU2753479C1 (ru) * | 2020-10-14 | 2021-08-17 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Пермская государственная фармацевтическая академия" Министерства здравоохранения Российской Федерации | 2-Амино-1-бензамидо-5-[2-(нафталин-1-ил)-2-оксоэтилиден]-4-оксо-4,5-дигидро-1Н-пиррол-3-карбоксамид, обладающий цитотоксическими и проапоптогенными свойствами в отношении клеток солидных опухолей человека, в том числе резистентных к химиопрепаратам |
| CN118510503A (zh) | 2022-02-25 | 2024-08-16 | 珠海贝海生物技术有限公司 | 多西他赛组合物和方法 |
| CN114588272B (zh) * | 2022-04-08 | 2023-05-26 | 皖西学院 | 一种负载no的多西紫杉醇纳米药物及其制备方法和应用 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9213077D0 (en) * | 1992-06-19 | 1992-08-05 | Erba Carlo Spa | Polymerbound taxol derivatives |
| CA2444483A1 (en) * | 2001-04-26 | 2002-11-07 | Board Of Regents, The University Of Texas System | Diagnostic imaging compositions, their methods of synthesis and use |
| US20080171067A1 (en) * | 2007-01-17 | 2008-07-17 | Immunomedics, Inc. | Polymeric Carriers of Therapeutic Agents and Recognition Moieties for Antibody-Based Targeting of Disease Sites |
| CZ2006207A3 (cs) * | 2006-03-28 | 2008-01-16 | Zentiva, A. S. | Micelární nosiče léčiv s protinádorovou aktivitou |
| CZ2006505A3 (cs) * | 2006-08-09 | 2008-04-09 | Zentiva, A. S. | Polymerní konjugáty doxorubicinu s pH-rízeným uvolnováním léciva a zpusob jejich prípravy |
| CZ298945B6 (cs) * | 2006-09-18 | 2008-03-19 | Zentiva, A. S. | Polymerní lécivo a zpusob jeho výroby |
| US8017141B2 (en) * | 2006-12-15 | 2011-09-13 | Advanced Cardiovascular Systems, Inc. | Coatings of acrylamide-based copolymers |
| CZ301004B6 (cs) * | 2007-06-27 | 2009-10-07 | Ústav experimentální botaniky AV CR v. v. i. | Cílené deriváty paclitaxelu, jejich zpusob výroby a jejich použití |
-
2009
- 2009-02-13 CZ CZ20090085A patent/CZ303072B6/cs not_active IP Right Cessation
-
2010
- 2010-02-09 UA UAA201115172A patent/UA104187C2/ru unknown
- 2010-02-09 EP EP10716267A patent/EP2413973A1/en not_active Withdrawn
- 2010-02-09 WO PCT/CZ2010/000014 patent/WO2010091650A1/en not_active Ceased
- 2010-02-09 EA EA201190315A patent/EA022803B1/ru not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CZ200985A3 (cs) | 2010-08-25 |
| EP2413973A1 (en) | 2012-02-08 |
| EA201190315A1 (ru) | 2012-05-30 |
| WO2010091650A1 (en) | 2010-08-19 |
| UA104187C2 (ru) | 2014-01-10 |
| CZ303072B6 (cs) | 2012-03-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Chen et al. | Enhanced tumour penetration and prolonged circulation in blood of polyzwitterion–drug conjugates with cell-membrane affinity | |
| Xie et al. | Furin-instructed aggregated gold nanoparticles for re-educating tumor associated macrophages and overcoming breast cancer chemoresistance | |
| EA022803B1 (ru) | ПОЛИМЕРНЫЕ КОНЪЮГАТЫ ПАКЛИТАКСЕЛЯ И ДОЦЕТАКСЕЛЯ С КОНТРОЛИРУЕМЫМ ПОД ДЕЙСТВИЕМ pH ВЫСВОБОЖДЕНИЕМ КАНЦЕРОСТАТИЧЕСКОГО АГЕНТА | |
| Shi et al. | Fullerene (C60)-based tumor-targeting nanoparticles with “off-on” state for enhanced treatment of cancer | |
| Sharma et al. | Dendrimer-mediated targeted delivery of rapamycin to tumor-associated macrophages improves systemic treatment of glioblastoma | |
| He et al. | Repurposing disulfiram for cancer therapy via targeted nanotechnology through enhanced tumor mass penetration and disassembly | |
| US11478493B2 (en) | Fabrication and application of a hetero-targeted nano-cocktail with traceless linkers | |
| Moon et al. | In vitro assessment of a novel polyrotaxane-based drug delivery system integrated with a cell-penetrating peptide | |
| Singh et al. | EGFR-targeted gelatin nanoparticles for systemic administration of gemcitabine in an orthotopic pancreatic cancer model | |
| AU2003230852B2 (en) | TNP-470 polymer conjugates and use thereof | |
| AU2017389094B2 (en) | Aptamer-drug conjugate and use thereof | |
| Shamay et al. | Inhibition of primary and metastatic tumors in mice by E-selectin-targeted polymer–drug conjugates | |
| Nakamura et al. | Pronounced cellular uptake of pirarubicin versus that of other anthracyclines: comparison of HPMA copolymer conjugates of pirarubicin and doxorubicin | |
| Chen et al. | Paclitaxel loaded phospholipid-based gel as a drug delivery system for local treatment of glioma | |
| CN103041402A (zh) | 通过间接化学轭合获得的透明质酸或其衍生物的抗肿瘤生物轭合物 | |
| Li et al. | Designing polymers with stimuli-responsive degradation for biomedical applications | |
| JP6462147B2 (ja) | Ｈｓｐ９０阻害ペプチド結合体及びその腫瘍治療における応用 | |
| Pickering et al. | Convection-Enhanced Delivery of Auristatin-Conjugated Layer-by-Layer Nanoparticles for Glioblastoma Treatment | |
| Kakinoki et al. | Synthesis and evaluation of water-soluble poly (vinyl alcohol)–paclitaxel conjugate as a macromolecular prodrug | |
| JP2010163417A (ja) | 標的タンパク質分解酵素感応型抗癌剤前駆体 | |
| CN113244175A (zh) | 一种免疫囊泡美登素偶联物及其制备方法与应用 | |
| Colombo et al. | Intraperitoneal administration of novel doxorubicin loaded polymeric delivery systems against peritoneal carcinomatosis: experimental study in a murine model of ovarian cancer | |
| CN113710323A (zh) | 偶联物及癌治疗剂 | |
| Viale et al. | Fibrin gels entrapment of a doxorubicin-containing targeted polycyclodextrin: Evaluation of in vivo antitumor activity in orthotopic models of human Neuroblastoma | |
| EP2349343B1 (en) | Polymeric composition with synergistic effect in treatment of tumour diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM AZ BY KZ KG MD TJ TM RU |