CN104367556B - 一种能提供一氧化氮的透明质酸硝酸酯去氧胆酸聚合物胶束的制备方法及其应用 - Google Patents
一种能提供一氧化氮的透明质酸硝酸酯去氧胆酸聚合物胶束的制备方法及其应用 Download PDFInfo
- Publication number
- CN104367556B CN104367556B CN201410647093.7A CN201410647093A CN104367556B CN 104367556 B CN104367556 B CN 104367556B CN 201410647093 A CN201410647093 A CN 201410647093A CN 104367556 B CN104367556 B CN 104367556B
- Authority
- CN
- China
- Prior art keywords
- hyaluronic acid
- nitrate
- polymer micelle
- deoxycholic acid
- deoxycholic
- 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
- 229920002674 hyaluronan Polymers 0.000 title claims abstract description 107
- 229960003160 hyaluronic acid Drugs 0.000 title claims abstract description 98
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 title claims abstract description 97
- 239000000693 micelle Substances 0.000 title claims abstract description 73
- 229960003964 deoxycholic acid Drugs 0.000 title claims abstract description 68
- 229920000642 polymer Polymers 0.000 title claims abstract description 56
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 title claims abstract description 39
- 229910002651 NO3 Inorganic materials 0.000 title claims abstract description 33
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 title claims abstract description 33
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 16
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 title claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 38
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- 229940079593 drug Drugs 0.000 claims abstract description 22
- 239000003960 organic solvent Substances 0.000 claims abstract description 20
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical class O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000002244 precipitate Substances 0.000 claims abstract description 14
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000004108 freeze drying Methods 0.000 claims abstract description 13
- 239000012153 distilled water Substances 0.000 claims abstract description 11
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 claims abstract description 11
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000001914 filtration Methods 0.000 claims abstract description 7
- 230000037452 priming Effects 0.000 claims abstract description 7
- 238000000502 dialysis Methods 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 16
- 229910017604 nitric acid Inorganic materials 0.000 claims description 16
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 230000000118 anti-neoplastic effect Effects 0.000 claims description 11
- 239000002246 antineoplastic agent Substances 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 238000003786 synthesis reaction Methods 0.000 claims description 8
- 229940041181 antineoplastic drug Drugs 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 7
- HAWSQZCWOQZXHI-FQEVSTJZSA-N 10-Hydroxycamptothecin Chemical compound C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-FQEVSTJZSA-N 0.000 claims 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 claims description 6
- 229930191701 arteannuin Natural products 0.000 claims description 6
- BLUAFEHZUWYNDE-NNWCWBAJSA-N artemisinin Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 claims description 6
- 229960004191 artemisinin Drugs 0.000 claims description 6
- 229960003668 docetaxel Drugs 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- 238000002512 chemotherapy Methods 0.000 claims description 5
- 229920000359 diblock copolymer Polymers 0.000 claims description 5
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 claims description 5
- 229940099552 hyaluronan Drugs 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 4
- 238000007385 chemical modification Methods 0.000 claims description 4
- 239000000376 reactant Substances 0.000 claims description 4
- 238000011938 amidation process Methods 0.000 claims description 3
- 239000012736 aqueous medium Substances 0.000 claims description 3
- 239000003560 cancer drug Substances 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 238000005192 partition Methods 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 238000000108 ultra-filtration Methods 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims 1
- 239000012046 mixed solvent Substances 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 abstract description 24
- 238000011282 treatment Methods 0.000 abstract description 16
- 230000008685 targeting Effects 0.000 abstract description 13
- 201000011510 cancer Diseases 0.000 abstract description 12
- -1 hyaluronic acid nitrates Chemical class 0.000 abstract description 4
- 238000010521 absorption reaction Methods 0.000 abstract description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 abstract 1
- 238000001556 precipitation Methods 0.000 abstract 1
- 229910052708 sodium Inorganic materials 0.000 abstract 1
- 239000011734 sodium Substances 0.000 abstract 1
- 210000004881 tumor cell Anatomy 0.000 description 17
- 239000002840 nitric oxide donor Substances 0.000 description 13
- 239000002253 acid Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000011068 loading method Methods 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 6
- 238000002798 spectrophotometry method Methods 0.000 description 5
- 238000001338 self-assembly Methods 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000002835 absorbance Methods 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 150000004676 glycans Chemical class 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- 230000010415 tropism Effects 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241001597008 Nomeidae Species 0.000 description 2
- 229930012538 Paclitaxel Natural products 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000005170 neoplastic cell Anatomy 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 229960001592 paclitaxel Drugs 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 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 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000012930 cell culture fluid Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002254 cytotoxic agent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000003969 glutathione Nutrition 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000002398 materia medica Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000003921 particle size analysis Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 238000009738 saturating Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims (6)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410647093.7A CN104367556B (zh) | 2014-11-14 | 2014-11-14 | 一种能提供一氧化氮的透明质酸硝酸酯去氧胆酸聚合物胶束的制备方法及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410647093.7A CN104367556B (zh) | 2014-11-14 | 2014-11-14 | 一种能提供一氧化氮的透明质酸硝酸酯去氧胆酸聚合物胶束的制备方法及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN104367556A CN104367556A (zh) | 2015-02-25 |
CN104367556B true CN104367556B (zh) | 2016-10-19 |
Family
ID=52546921
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410647093.7A Expired - Fee Related CN104367556B (zh) | 2014-11-14 | 2014-11-14 | 一种能提供一氧化氮的透明质酸硝酸酯去氧胆酸聚合物胶束的制备方法及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN104367556B (zh) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106177987B (zh) * | 2016-08-17 | 2020-06-12 | 上海交通大学 | 小分子-高分子轭合物自组装载药纳米颗粒及其制备方法 |
CN106729745B (zh) * | 2016-12-28 | 2020-04-21 | 郑州大学 | 一种基于透明质酸修饰的能够递送一氧化氮的胶束的制备方法与应用 |
CN113304123A (zh) * | 2021-06-04 | 2021-08-27 | 郑州大学 | 共载jtc801和dna甲基化转移酶抑制剂的仿生纳米药物及制备方法与应用 |
CN115120611B (zh) * | 2022-09-01 | 2022-12-02 | 江西中医药大学 | 一种no供体型胶束组合物及其制备方法与应用 |
CN115850534B (zh) * | 2022-12-16 | 2024-03-12 | 浙江大学 | 一种透明质酸-胆酸衍生物及其合成方法和应用 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1948331A (zh) * | 2005-10-13 | 2007-04-18 | 中国人民解放军军事医学科学院毒物药物研究所 | 胆汁酸的硝酸酯衍生物及其医药用途 |
CN101745119A (zh) * | 2010-01-25 | 2010-06-23 | 中国药科大学 | 羧酸类药物-多糖偶联物及其制备方法与应用 |
CN102125547A (zh) * | 2010-12-22 | 2011-07-20 | 中国药科大学 | 一种含藤黄酸类药物的药物组合物及其制备方法 |
CN103030140A (zh) * | 2012-12-21 | 2013-04-10 | 郑州大学 | 透明质酸修饰的氧化石墨烯及其药物组合物的制备方法与应用 |
-
2014
- 2014-11-14 CN CN201410647093.7A patent/CN104367556B/zh not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1948331A (zh) * | 2005-10-13 | 2007-04-18 | 中国人民解放军军事医学科学院毒物药物研究所 | 胆汁酸的硝酸酯衍生物及其医药用途 |
CN101745119A (zh) * | 2010-01-25 | 2010-06-23 | 中国药科大学 | 羧酸类药物-多糖偶联物及其制备方法与应用 |
CN102125547A (zh) * | 2010-12-22 | 2011-07-20 | 中国药科大学 | 一种含藤黄酸类药物的药物组合物及其制备方法 |
CN103030140A (zh) * | 2012-12-21 | 2013-04-10 | 郑州大学 | 透明质酸修饰的氧化石墨烯及其药物组合物的制备方法与应用 |
Non-Patent Citations (1)
Title |
---|
硝酸酯偶联药物的研究进展;李宏武等;《军事医学科学院院刊》;20050831;第29卷(第4期);参见全文 * |
Also Published As
Publication number | Publication date |
---|---|
CN104367556A (zh) | 2015-02-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Fang et al. | In vitro/vivo evaluation of novel mitochondrial targeting charge-reversal polysaccharide-based antitumor nanoparticle | |
CN101791411B (zh) | 两亲性多糖偶联物及其药物组合物的制备和应用 | |
CN104367556B (zh) | 一种能提供一氧化氮的透明质酸硝酸酯去氧胆酸聚合物胶束的制备方法及其应用 | |
CN108379228B (zh) | 一种包裹药理活性物质的白蛋白纳米颗粒及其制备方法和应用 | |
CN105727309A (zh) | 双敏感两亲性多糖-阿霉素偶联物及其药学组合物的制备和应用 | |
Gotov et al. | Hyaluronic acid-coated cisplatin conjugated gold nanoparticles for combined cancer treatment | |
Ling et al. | Tumor-targeting delivery of hyaluronic acid–platinum (iv) nanoconjugate to reduce toxicity and improve survival | |
Zheng et al. | Advances in tracking of polysaccharides in vivo: Labeling strategies, potential factors and applications based on pharmacokinetic characteristics | |
CN101732728B (zh) | 抗炎药物-多糖偶联物及其药物组合物的制备和应用 | |
CN103768080B (zh) | 一种抗耐药肿瘤的靶向制剂、制备方法及应用 | |
CN109875964B (zh) | 一种阿霉素无载体纳米药物的制备及其应用 | |
CN104940945B (zh) | 一种透明质酸修饰的中空介孔硫化铜复合物及其制备方法与应用 | |
CN103611165A (zh) | 透明质酸-环糊精-金刚烷聚乙二醇载体及其制备方法和应用 | |
CN105012271A (zh) | 一种共担载阿霉素和trail的白蛋白纳米粒靶向制剂及制备方法 | |
CN114748639B (zh) | 一种光敏剂-羟烷基淀粉-多肽偶联的两亲性大分子化合物、纳米载药***及其制备方法 | |
CN107096036A (zh) | 一种pH敏感型透明质酸‑多柔比星纳米前药的制备方法及其应用 | |
CN110063933A (zh) | 一种葡聚糖基纳米凝胶及其制备方法和应用 | |
Wu et al. | Polysaccharide-based tumor microenvironment-responsive drug delivery systems for cancer therapy | |
CN104491875A (zh) | 一种基于透明质酸-难溶性药物前药的自聚纳米***的制备方法 | |
Park et al. | Self-assembled nanocomplex of PEGylated protamine and heparin–suramin conjugate for accumulation at the tumor site | |
CN105126121B (zh) | 一种靶向金银合金纳米笼的药物递送***的制备方法及应用 | |
Wang et al. | A conveniently synthesized Pt (IV) conjugated alginate nanoparticle with ligand self-shielded property for targeting treatment of hepatic carcinoma | |
Li et al. | Temperature-and pH-responsive injectable chitosan hydrogels loaded with doxorubicin and curcumin as long-lasting release platforms for the treatment of solid tumors | |
Zhao et al. | Targeting delivery of partial VAR2CSA peptide guided N-2-Hydroxypropyl trimethyl ammonium chloride chitosan nanoparticles for multiple cancer types | |
CN107158404A (zh) | 一种应用于肝癌化疗联合给药的肝靶向pH敏感性纳米粒子给药***及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
CB03 | Change of inventor or designer information |
Inventor after: Zhang Zhenzhong Inventor after: Zhang Huijuan Inventor after: Guo Jimin Inventor after: Jiao Xiaojing Inventor after: Chen Qianqian Inventor after: Ji Yandan Inventor after: Zhang Hongling Inventor after: Hou Lin Inventor before: Zhang Huijuan Inventor before: Jiao Xiaojing Inventor before: Chen Qianqian Inventor before: Ji Yandan Inventor before: Zhang Zhenzhong Inventor before: Zhang Hongling Inventor before: Hou Lin |
|
COR | Change of bibliographic data | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CP02 | Change in the address of a patent holder |
Address after: 450001 Zhengzhou science and Technology Development Zone, Henan, No. 100 science Avenue Patentee after: Zhengzhou University Address before: 450001 science avenue of Zhengzhou high tech Development Zone, Zhengzhou, Henan Province, No. Patentee before: Zhengzhou University |
|
CP02 | Change in the address of a patent holder | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20161019 Termination date: 20171114 |
|
CF01 | Termination of patent right due to non-payment of annual fee |