CA2387611C - Manufacture of polyglutamate-therapeutic agent conjugates - Google Patents
Manufacture of polyglutamate-therapeutic agent conjugates Download PDFInfo
- Publication number
- CA2387611C CA2387611C CA2387611A CA2387611A CA2387611C CA 2387611 C CA2387611 C CA 2387611C CA 2387611 A CA2387611 A CA 2387611A CA 2387611 A CA2387611 A CA 2387611A CA 2387611 C CA2387611 C CA 2387611C
- Authority
- CA
- Canada
- Prior art keywords
- conjugate
- camptothecin
- polyglutamic acid
- acid
- hydroxycamptothecin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- 239000003814 drug Substances 0.000 title abstract description 63
- 229940124597 therapeutic agent Drugs 0.000 title abstract description 58
- 238000000034 method Methods 0.000 claims abstract description 49
- 229920002643 polyglutamic acid Polymers 0.000 claims description 78
- 108010020346 Polyglutamic Acid Proteins 0.000 claims description 47
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 43
- 229920000642 polymer Polymers 0.000 claims description 40
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 37
- 229940127093 camptothecin Drugs 0.000 claims description 31
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 14
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 10
- 230000021615 conjugation Effects 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- 239000004471 Glycine Substances 0.000 claims description 7
- 229950009213 rubitecan Drugs 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 5
- FJHBVJOVLFPMQE-QFIPXVFZSA-N 7-Ethyl-10-Hydroxy-Camptothecin Chemical compound C1=C(O)C=C2C(CC)=C(CN3C(C4=C([C@@](C(=O)OC4)(O)CC)C=C33)=O)C3=NC2=C1 FJHBVJOVLFPMQE-QFIPXVFZSA-N 0.000 claims description 4
- FUXVKZWTXQUGMW-FQEVSTJZSA-N 9-Aminocamptothecin Chemical compound C1=CC(N)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 FUXVKZWTXQUGMW-FQEVSTJZSA-N 0.000 claims description 4
- RPFYDENHBPRCTN-NRFANRHFSA-N mdo-cpt Chemical compound C1=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=CC2=C1OCO2 RPFYDENHBPRCTN-NRFANRHFSA-N 0.000 claims description 4
- VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims 4
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims 4
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- 238000005481 NMR spectroscopy Methods 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- -1 improved solubility Chemical class 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
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- 239000012266 salt solution Substances 0.000 description 9
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 8
- MZNMZWZGUGFQJP-UHFFFAOYSA-N 1-[11-(dodecylamino)-10-hydroxyundecyl]-3,7-dimethylpurine-2,6-dione Chemical compound O=C1N(CCCCCCCCCC(O)CNCCCCCCCCCCCC)C(=O)N(C)C2=C1N(C)C=N2 MZNMZWZGUGFQJP-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 238000002835 absorbance Methods 0.000 description 8
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 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 description 6
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- TXFOLHZMICYNRM-UHFFFAOYSA-N dichlorophosphoryloxybenzene Chemical compound ClP(Cl)(=O)OC1=CC=CC=C1 TXFOLHZMICYNRM-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 1
- GCSAXWHQFYOIFE-UHFFFAOYSA-N dipyridin-2-yl carbonate Chemical compound C=1C=CC=NC=1OC(=O)OC1=CC=CC=N1 GCSAXWHQFYOIFE-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
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- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
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- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- JDNTWHVOXJZDSN-UHFFFAOYSA-N iodoacetic acid Chemical compound OC(=O)CI JDNTWHVOXJZDSN-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000005007 materials handling Methods 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- HNEGQIOMVPPMNR-NSCUHMNNSA-N mesaconic acid Chemical compound OC(=O)C(/C)=C/C(O)=O HNEGQIOMVPPMNR-NSCUHMNNSA-N 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- HNEGQIOMVPPMNR-UHFFFAOYSA-N methylfumaric acid Natural products OC(=O)C(C)=CC(O)=O HNEGQIOMVPPMNR-UHFFFAOYSA-N 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
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- 210000003205 muscle Anatomy 0.000 description 1
- 230000008634 non enzymatic mechanism Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
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- 239000012044 organic layer Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical class C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
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- 230000001105 regulatory effect Effects 0.000 description 1
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- 239000000523 sample Substances 0.000 description 1
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- 238000001374 small-angle light scattering Methods 0.000 description 1
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- 235000011152 sodium sulphate Nutrition 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
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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
-
- 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
-
- 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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Polyamides (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US15913599P | 1999-10-12 | 1999-10-12 | |
| US60/159,135 | 1999-10-12 | ||
| PCT/US2000/028109 WO2001026693A2 (en) | 1999-10-12 | 2000-10-12 | Manufacture of polyglutamate-therapeutic agent conjugates |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2387611A1 CA2387611A1 (en) | 2001-04-19 |
| CA2387611C true CA2387611C (en) | 2011-03-29 |
Family
ID=22571222
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2387611A Expired - Fee Related CA2387611C (en) | 1999-10-12 | 2000-10-12 | Manufacture of polyglutamate-therapeutic agent conjugates |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US20020077279A1 (enExample) |
| EP (2) | EP1466627A1 (enExample) |
| JP (1) | JP2003511423A (enExample) |
| KR (1) | KR100821437B1 (enExample) |
| CN (2) | CN1607962A (enExample) |
| AU (1) | AU781735B2 (enExample) |
| BR (1) | BRPI0014652B1 (enExample) |
| CA (1) | CA2387611C (enExample) |
| HU (1) | HUP0203123A3 (enExample) |
| MX (1) | MXPA02003719A (enExample) |
| NO (1) | NO20021701L (enExample) |
| NZ (1) | NZ529789A (enExample) |
| PL (1) | PL354623A1 (enExample) |
| SG (1) | SG147286A1 (enExample) |
| WO (1) | WO2001026693A2 (enExample) |
| ZA (1) | ZA200202695B (enExample) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2001095943A2 (en) | 2000-06-14 | 2001-12-20 | Medarex, Inc. | Prodrug compounds with an oligopeptide having an isoleucine residue |
| US6872715B2 (en) | 2001-08-06 | 2005-03-29 | Kosan Biosciences, Inc. | Benzoquinone ansamycins |
| JP4578470B2 (ja) | 2003-04-22 | 2010-11-10 | イプセン ファルマ ソシエテ パール アクシオン サンプリフィエ | ソマトスタチンベクター |
| FR2855521B1 (fr) * | 2003-05-28 | 2005-08-05 | Flamel Tech Sa | Polyaminoacides fonctionnalises par au moins un groupement h ydrophobe et leurs applications notamment therapeutiques. |
| US7259156B2 (en) | 2004-05-20 | 2007-08-21 | Kosan Biosciences Incorporated | Geldanamycin compounds and method of use |
| US8614228B2 (en) | 2004-08-11 | 2013-12-24 | Arqule, Inc. | Quinone prodrug compositions and methods of use |
| WO2006020719A2 (en) | 2004-08-11 | 2006-02-23 | Arqule, Inc. | Aminoacid conjugates of beta - lapachone for tumor targeting |
| AU2005285953B2 (en) | 2004-09-22 | 2011-01-20 | Nippon Kayaku Kabushiki Kaisha | Novel block copolymer, micelle preparation, and anticancer agent containing the same as active ingredient |
| ATE432955T1 (de) | 2005-12-05 | 2009-06-15 | Nitto Denko Corp | Polyglutamat-aminosäure-konjugate und verfahren |
| KR20080074202A (ko) * | 2005-12-06 | 2008-08-12 | 셀 쎄러퓨틱스 인코포레이티드 | 에스트로겐 암 요법 |
| US7462627B2 (en) * | 2006-02-09 | 2008-12-09 | Enzon Pharmaceuticals, Inc. | Multi-arm polymeric conjugates of 7-ethyl-10-hydroxycamptothecin for treatment of breast, colorectal, pancreatic, ovarian and lung cancers |
| US7671067B2 (en) * | 2006-02-09 | 2010-03-02 | Enzon Pharmaceuticals, Inc. | Treatment of non-hodgkin's lymphomas with multi-arm polymeric conjugates of 7-ethyl-10-hydroxycamtothecin |
| US8323669B2 (en) | 2006-03-28 | 2012-12-04 | Nippon Kayaku Kabushiki Kaisha | Polymer conjugate of taxane |
| CN101448875A (zh) | 2006-05-18 | 2009-06-03 | 日本化药株式会社 | 鬼臼毒素类的高分子量结合体 |
| WO2008056596A1 (fr) | 2006-11-06 | 2008-05-15 | Nippon Kayaku Kabushiki Kaisha | Dérivé polymère d'un antagoniste métabolique d'acide nucléique |
| WO2008056654A1 (fr) | 2006-11-08 | 2008-05-15 | Nippon Kayaku Kabushiki Kaisha | Dérivé polymère d'un antagoniste métabolique d'acide nucléique |
| CN101209350B (zh) * | 2006-12-30 | 2011-09-07 | 中国人民解放军军事医学科学院毒物药物研究所 | 以氨基酸为连接子的多聚谷氨酸-药物偶合物 |
| US7928095B2 (en) * | 2007-02-09 | 2011-04-19 | Enzon Pharmaceuticals, Inc. | Treatment of resistant or refractory cancers with multi-arm polymeric conjugates of 7-ethyl-10-hydroxycamptothecin |
| CN101674852A (zh) * | 2007-04-10 | 2010-03-17 | 日东电工株式会社 | 多功能聚谷氨酸盐药物载体 |
| CA2685739C (en) | 2007-04-30 | 2016-06-14 | Arqule, Inc | Hydroxy sulfonate of quinone compounds and their uses |
| CA2683590A1 (en) * | 2007-05-09 | 2008-11-20 | Nitto Denko Corporation | Compositions that include a hydrophobic compound and a polyamino acid conjugate |
| CN101707869A (zh) * | 2007-05-09 | 2010-05-12 | 日东电工株式会社 | 具有多种药物的聚谷氨酸盐结合物和聚谷氨酸盐-氨基酸结合物 |
| EP2155254B1 (en) * | 2007-05-09 | 2012-11-28 | Nitto Denko Corporation | Polymers conjugated with platinum drugs |
| WO2009041570A1 (ja) | 2007-09-28 | 2009-04-02 | Nippon Kayaku Kabushiki Kaisha | ステロイド類の高分子結合体 |
| JP2011513412A (ja) * | 2008-03-06 | 2011-04-28 | 日東電工株式会社 | ポリマーパクリタキセル結合体を含む癌を治療するための薬学組成物 |
| KR101589582B1 (ko) | 2008-03-18 | 2016-01-28 | 니폰 가야꾸 가부시끼가이샤 | 생리활성물질의 고분자량 결합체 |
| WO2009136572A1 (ja) | 2008-05-08 | 2009-11-12 | 日本化薬株式会社 | 葉酸若しくは葉酸誘導体の高分子結合体 |
| US20100056555A1 (en) * | 2008-08-29 | 2010-03-04 | Enzon Pharmaceuticals, Inc. | Method of treating ras associated cancer |
| KR101705077B1 (ko) | 2008-10-07 | 2017-02-09 | 렉산 파마슈티컬스, 인코포레이티드 | Ｈｐｍａ-도세탁셀 또는 젬시타빈 컨쥬게이트 및 이의 용도 |
| CN102176923A (zh) * | 2008-10-15 | 2011-09-07 | 日东电工株式会社 | 制备聚谷氨酸酯结合物的方法 |
| CN102215688A (zh) * | 2008-10-21 | 2011-10-12 | 安龙制药公司 | 用7-乙基-10-羟基喜树碱的多臂聚合物对神经母细胞瘤的治疗 |
| DE102008060549A1 (de) * | 2008-12-04 | 2010-06-10 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Wirkstoff-Peptid-Konstrukt zur extrazellulären Anreicherung |
| US8808749B2 (en) | 2009-05-15 | 2014-08-19 | Nippon Kayaku Kabushiki Kaisha | Polymer conjugate of bioactive substance having hydroxy group |
| MX2012004416A (es) | 2009-10-13 | 2012-05-08 | Rexahn Pharmaceuticals Inc | Sistemas polimericos para el suministro de agentes anticancer. |
| MX2012010448A (es) * | 2010-03-11 | 2012-12-05 | Nitto Denko Corp | Conjugados de carbohidrato-poli aminoacido-farmaco. |
| EP2552967A4 (en) | 2010-04-02 | 2014-10-08 | Amunix Operating Inc | BINDING FUSION PROTEINS, BINDING FUSION PROTEIN MEDICINAL CONJUGATES, XTEN MEDICAMENT CONJUGATES, AND METHOD FOR THEIR PREPARATION AND USE |
| CN103221054A (zh) | 2010-11-17 | 2013-07-24 | 日本化药株式会社 | 新的胞苷类代谢拮抗剂的高分子衍生物 |
| CN102649810A (zh) * | 2011-05-19 | 2012-08-29 | 东北林业大学 | 喜树碱衍生物、其制备方法和用途 |
| US8691284B2 (en) | 2011-07-07 | 2014-04-08 | Empire Technology Development Llc | Fluorinated block co-polymers |
| JP5711378B2 (ja) | 2011-09-11 | 2015-04-30 | 日本化薬株式会社 | ブロック共重合体の製造方法 |
| US8383093B1 (en) | 2011-11-01 | 2013-02-26 | Serina Therapeutics, Inc. | Subcutaneous delivery of poly(oxazoline) conjugates |
| US8907045B2 (en) | 2012-04-03 | 2014-12-09 | Empire Technology Development Llc | Biocompatible adhesive polymers |
| JP2016520687A (ja) | 2013-04-26 | 2016-07-14 | 日東電工株式会社 | ポリアニオン性ポリマー結合体からのエンドトキシンの減少 |
| KR101507119B1 (ko) * | 2013-05-31 | 2015-03-30 | 주식회사 바이오리더스 | 점막 점착성 폴리감마글루탐산 나노마이셀 및 이를 이용한 약물 전달체 |
| CN106267227A (zh) * | 2016-08-12 | 2017-01-04 | 北京蓝贝望生物医药科技股份有限公司 | 抗肿瘤药物 |
| CN106750272B (zh) * | 2016-12-05 | 2019-05-28 | 福建卫生职业技术学院 | 一种水溶性蛇葡萄素聚合物 |
| CN110123748A (zh) * | 2019-04-22 | 2019-08-16 | 南京师范大学 | 一种叶酸介导的靶向双载药聚合物胶束及其制备方法和应用 |
| CN113773282A (zh) * | 2021-09-22 | 2021-12-10 | 无锡紫杉药业有限公司 | 一种10-乙酰紫杉醇的制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4356166A (en) * | 1978-12-08 | 1982-10-26 | University Of Utah | Time-release chemical delivery system |
| US5629433A (en) * | 1994-07-18 | 1997-05-13 | Hauser, Inc. | Selective process for the deacylation and deacetylation of taxol and taxanes |
| CA2192725C (en) * | 1995-12-28 | 2004-04-20 | Kenji Tsujihara | Camptothecin derivatives |
| WO1997033552A1 (en) * | 1996-03-12 | 1997-09-18 | Pg-Txl Company, L.P. | Water soluble paclitaxel prodrugs |
| US6441025B2 (en) * | 1996-03-12 | 2002-08-27 | Pg-Txl Company, L.P. | Water soluble paclitaxel derivatives |
| CA2402643A1 (en) * | 2000-03-17 | 2001-09-27 | Cell Therapeutics, Inc. | Polyglutamic acid-camptothecin conjugates and methods of preparation |
-
2000
- 2000-10-12 JP JP2001529754A patent/JP2003511423A/ja active Pending
- 2000-10-12 HU HU0203123A patent/HUP0203123A3/hu unknown
- 2000-10-12 EP EP04013703A patent/EP1466627A1/en not_active Withdrawn
- 2000-10-12 CN CNA008170290A patent/CN1607962A/zh active Pending
- 2000-10-12 KR KR1020027004640A patent/KR100821437B1/ko not_active Expired - Fee Related
- 2000-10-12 CN CNA2009101276554A patent/CN101507820A/zh active Pending
- 2000-10-12 AU AU10793/01A patent/AU781735B2/en not_active Ceased
- 2000-10-12 SG SG200401981-6A patent/SG147286A1/en unknown
- 2000-10-12 WO PCT/US2000/028109 patent/WO2001026693A2/en not_active Ceased
- 2000-10-12 EP EP00972079A patent/EP1225917A2/en not_active Withdrawn
- 2000-10-12 BR BRPI0014652A patent/BRPI0014652B1/pt not_active IP Right Cessation
- 2000-10-12 NZ NZ529789A patent/NZ529789A/en not_active IP Right Cessation
- 2000-10-12 CA CA2387611A patent/CA2387611C/en not_active Expired - Fee Related
- 2000-10-12 PL PL00354623A patent/PL354623A1/xx not_active IP Right Cessation
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2001
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2002
- 2002-04-05 ZA ZA200202695A patent/ZA200202695B/en unknown
- 2002-04-11 NO NO20021701A patent/NO20021701L/no not_active Application Discontinuation
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2003
- 2003-04-02 US US10/404,152 patent/US7399860B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0014652B1 (pt) | 2016-08-09 |
| ZA200202695B (en) | 2004-02-25 |
| MXPA02003719A (es) | 2002-08-30 |
| BR0014652A (pt) | 2003-06-10 |
| SG147286A1 (en) | 2008-11-28 |
| KR20020059616A (ko) | 2002-07-13 |
| KR100821437B1 (ko) | 2008-04-10 |
| US20030224971A1 (en) | 2003-12-04 |
| NO20021701L (no) | 2002-05-23 |
| HUP0203123A2 (hu) | 2003-01-28 |
| EP1225917A2 (en) | 2002-07-31 |
| CN101507820A (zh) | 2009-08-19 |
| US7399860B2 (en) | 2008-07-15 |
| EP1466627A1 (en) | 2004-10-13 |
| US20020077279A1 (en) | 2002-06-20 |
| NO20021701D0 (no) | 2002-04-11 |
| AU1079301A (en) | 2001-04-23 |
| CA2387611A1 (en) | 2001-04-19 |
| WO2001026693A3 (en) | 2001-12-27 |
| PL354623A1 (en) | 2004-02-09 |
| AU781735B2 (en) | 2005-06-09 |
| JP2003511423A (ja) | 2003-03-25 |
| WO2001026693A2 (en) | 2001-04-19 |
| NZ529789A (en) | 2005-04-29 |
| HUP0203123A3 (en) | 2004-12-28 |
| CN1607962A (zh) | 2005-04-20 |
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