JP2015514059A - 多糖ナノ粒子の調製方法 - Google Patents
多糖ナノ粒子の調製方法 Download PDFInfo
- Publication number
- JP2015514059A JP2015514059A JP2015500386A JP2015500386A JP2015514059A JP 2015514059 A JP2015514059 A JP 2015514059A JP 2015500386 A JP2015500386 A JP 2015500386A JP 2015500386 A JP2015500386 A JP 2015500386A JP 2015514059 A JP2015514059 A JP 2015514059A
- Authority
- JP
- Japan
- Prior art keywords
- group
- active substance
- derivatives
- polysaccharide
- solution
- 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.)
- Granted
Links
- 239000002105 nanoparticle Substances 0.000 title claims abstract description 62
- 238000000034 method Methods 0.000 title claims abstract description 46
- 229920001282 polysaccharide Polymers 0.000 title claims abstract description 43
- 239000005017 polysaccharide Substances 0.000 title claims abstract description 43
- 150000004676 glycans Chemical class 0.000 title abstract description 9
- 125000003172 aldehyde group Chemical group 0.000 claims abstract description 48
- 238000006243 chemical reaction Methods 0.000 claims abstract description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000007254 oxidation reaction Methods 0.000 claims abstract description 25
- 239000013543 active substance Substances 0.000 claims abstract description 24
- 230000003647 oxidation Effects 0.000 claims abstract description 24
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 125000003277 amino group Chemical group 0.000 claims abstract description 11
- -1 aromatic organic acids Chemical class 0.000 claims abstract description 11
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 9
- 150000001412 amines Chemical class 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 6
- 150000001413 amino acids Chemical class 0.000 claims abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract description 5
- 150000001408 amides Chemical class 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 4
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000003118 aryl group Chemical group 0.000 claims abstract description 3
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 claims abstract description 3
- 235000005985 organic acids Nutrition 0.000 claims abstract description 3
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims abstract description 3
- 150000004804 polysaccharides Chemical class 0.000 claims description 44
- 239000000243 solution Substances 0.000 claims description 29
- 229920002307 Dextran Polymers 0.000 claims description 28
- 239000003814 drug Substances 0.000 claims description 20
- 229940079593 drug Drugs 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 239000007864 aqueous solution Substances 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 12
- 108090000623 proteins and genes Proteins 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 238000000502 dialysis Methods 0.000 claims description 8
- 235000018102 proteins Nutrition 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 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 claims description 5
- XJGFWWJLMVZSIG-UHFFFAOYSA-N 9-aminoacridine Chemical compound C1=CC=C2C(N)=C(C=CC=C3)C3=NC2=C1 XJGFWWJLMVZSIG-UHFFFAOYSA-N 0.000 claims description 5
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 5
- 229920002472 Starch Polymers 0.000 claims description 5
- 235000004279 alanine Nutrition 0.000 claims description 5
- 235000001014 amino acid Nutrition 0.000 claims description 5
- 229940024606 amino acid Drugs 0.000 claims description 5
- 229960001441 aminoacridine Drugs 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- 108010092160 Dactinomycin Proteins 0.000 claims description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 4
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical group CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims description 4
- 239000001913 cellulose Substances 0.000 claims description 4
- 229920002678 cellulose Polymers 0.000 claims description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 4
- 229920002674 hyaluronan Polymers 0.000 claims description 4
- 229960003160 hyaluronic acid Drugs 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- DPBLXKKOBLCELK-UHFFFAOYSA-N pentan-1-amine Chemical compound CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 claims description 4
- 229910002651 NO3 Inorganic materials 0.000 claims description 3
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 239000000975 dye Substances 0.000 claims description 3
- 239000012634 fragment Substances 0.000 claims description 3
- 238000004108 freeze drying Methods 0.000 claims description 3
- 238000001415 gene therapy Methods 0.000 claims description 3
- HSEMFIZWXHQJAE-UHFFFAOYSA-N hexadecanamide Chemical compound CCCCCCCCCCCCCCCC(N)=O HSEMFIZWXHQJAE-UHFFFAOYSA-N 0.000 claims description 3
- IOQPZZOEVPZRBK-UHFFFAOYSA-N octan-1-amine Chemical compound CCCCCCCCN IOQPZZOEVPZRBK-UHFFFAOYSA-N 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 claims description 2
- GEYKZYNEWQWLTF-KTKRTIGZSA-N (z)-octadec-9-enehydrazide Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)NN GEYKZYNEWQWLTF-KTKRTIGZSA-N 0.000 claims description 2
- FJLUATLTXUNBOT-UHFFFAOYSA-N 1-Hexadecylamine Chemical compound CCCCCCCCCCCCCCCCN FJLUATLTXUNBOT-UHFFFAOYSA-N 0.000 claims description 2
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 claims description 2
- CFWRDBDJAOHXSH-SECBINFHSA-N 2-azaniumylethyl [(2r)-2,3-diacetyloxypropyl] phosphate Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-SECBINFHSA-N 0.000 claims description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 claims description 2
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 2
- 229920000856 Amylose Polymers 0.000 claims description 2
- 108010006654 Bleomycin Proteins 0.000 claims description 2
- 241000206575 Chondrus crispus Species 0.000 claims description 2
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 claims description 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 2
- MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 claims description 2
- MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 claims description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 2
- 229920002527 Glycogen Polymers 0.000 claims description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 2
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 2
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 2
- 239000002147 L01XE04 - Sunitinib Substances 0.000 claims description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 2
- 229930192392 Mitomycin Natural products 0.000 claims description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 2
- OJGMBLNIHDZDGS-UHFFFAOYSA-N N-Ethylaniline Chemical compound CCNC1=CC=CC=C1 OJGMBLNIHDZDGS-UHFFFAOYSA-N 0.000 claims description 2
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 claims description 2
- PLZVEHJLHYMBBY-UHFFFAOYSA-N Tetradecylamine Chemical compound CCCCCCCCCCCCCCN PLZVEHJLHYMBBY-UHFFFAOYSA-N 0.000 claims description 2
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 claims description 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 2
- 229960004150 aciclovir Drugs 0.000 claims description 2
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 2
- 239000000999 acridine dye Substances 0.000 claims description 2
- 229930183665 actinomycin Natural products 0.000 claims description 2
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 claims description 2
- 239000000783 alginic acid Substances 0.000 claims description 2
- 229920000615 alginic acid Polymers 0.000 claims description 2
- 235000010443 alginic acid Nutrition 0.000 claims description 2
- 229960001126 alginic acid Drugs 0.000 claims description 2
- 150000004781 alginic acids Chemical class 0.000 claims description 2
- 229960001561 bleomycin Drugs 0.000 claims description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 2
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 2
- 229960000590 celecoxib Drugs 0.000 claims description 2
- 238000005119 centrifugation Methods 0.000 claims description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 2
- 229960004316 cisplatin Drugs 0.000 claims description 2
- 229960002436 cladribine Drugs 0.000 claims description 2
- 239000002577 cryoprotective agent Substances 0.000 claims description 2
- 229960000684 cytarabine Drugs 0.000 claims description 2
- 229960000640 dactinomycin Drugs 0.000 claims description 2
- 229960000860 dapsone Drugs 0.000 claims description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 2
- 229960000975 daunorubicin Drugs 0.000 claims description 2
- JRBPAEWTRLWTQC-UHFFFAOYSA-N dodecylamine Chemical compound CCCCCCCCCCCCN JRBPAEWTRLWTQC-UHFFFAOYSA-N 0.000 claims description 2
- 229960004679 doxorubicin Drugs 0.000 claims description 2
- 229960002949 fluorouracil Drugs 0.000 claims description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 2
- 229960005277 gemcitabine Drugs 0.000 claims description 2
- 229940096919 glycogen Drugs 0.000 claims description 2
- 229960002897 heparin Drugs 0.000 claims description 2
- 229920000669 heparin Polymers 0.000 claims description 2
- SSVSELJXJJCANX-UHFFFAOYSA-N hexadecanehydrazide Chemical compound CCCCCCCCCCCCCCCC(=O)NN SSVSELJXJJCANX-UHFFFAOYSA-N 0.000 claims description 2
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims description 2
- 229960002411 imatinib Drugs 0.000 claims description 2
- 229960000310 isoleucine Drugs 0.000 claims description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 2
- 229960003350 isoniazid Drugs 0.000 claims description 2
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 claims description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 2
- 229960001924 melphalan Drugs 0.000 claims description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 claims description 2
- 229960001428 mercaptopurine Drugs 0.000 claims description 2
- 229930182817 methionine Natural products 0.000 claims description 2
- 229960000485 methotrexate Drugs 0.000 claims description 2
- 229960004857 mitomycin Drugs 0.000 claims description 2
- IXOXBSCIXZEQEQ-UHTZMRCNSA-N nelarabine Chemical compound C1=NC=2C(OC)=NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O IXOXBSCIXZEQEQ-UHTZMRCNSA-N 0.000 claims description 2
- 229960000801 nelarabine Drugs 0.000 claims description 2
- PGSADBUBUOPOJS-UHFFFAOYSA-N neutral red Chemical compound Cl.C1=C(C)C(N)=CC2=NC3=CC(N(C)C)=CC=C3N=C21 PGSADBUBUOPOJS-UHFFFAOYSA-N 0.000 claims description 2
- BYTFESSQUGDMQQ-UHFFFAOYSA-N octadecanehydrazide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NN BYTFESSQUGDMQQ-UHFFFAOYSA-N 0.000 claims description 2
- FATBGEAMYMYZAF-KTKRTIGZSA-N oleamide Chemical compound CCCCCCCC\C=C/CCCCCCCC(N)=O FATBGEAMYMYZAF-KTKRTIGZSA-N 0.000 claims description 2
- 229940100684 pentylamine Drugs 0.000 claims description 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 2
- 238000001556 precipitation Methods 0.000 claims description 2
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 claims description 2
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 claims description 2
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 claims description 2
- 229960001796 sunitinib Drugs 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 229960004964 temozolomide Drugs 0.000 claims description 2
- 239000004474 valine Substances 0.000 claims description 2
- 229960002555 zidovudine Drugs 0.000 claims description 2
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims 1
- 230000002528 anti-freeze Effects 0.000 claims 1
- 229910052802 copper Inorganic materials 0.000 claims 1
- 239000010949 copper Substances 0.000 claims 1
- 239000011877 solvent mixture Substances 0.000 claims 1
- 239000002245 particle Substances 0.000 abstract description 5
- 230000008878 coupling Effects 0.000 abstract 1
- 238000010168 coupling process Methods 0.000 abstract 1
- 238000005859 coupling reaction Methods 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 12
- 206010028980 Neoplasm Diseases 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 7
- 230000021615 conjugation Effects 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 238000009826 distribution Methods 0.000 description 5
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.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 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 3
- 229940105329 carboxymethylcellulose Drugs 0.000 description 3
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 3
- 150000002772 monosaccharides Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- NAALWFYYHHJEFQ-ZASNTINBSA-N (2s,5r,6r)-6-[[(2r)-2-[[6-[4-[bis(2-hydroxyethyl)sulfamoyl]phenyl]-2-oxo-1h-pyridine-3-carbonyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC(O)=CC=1)C(=O)C(C(N1)=O)=CC=C1C1=CC=C(S(=O)(=O)N(CCO)CCO)C=C1 NAALWFYYHHJEFQ-ZASNTINBSA-N 0.000 description 2
- IZBZQUREHISXFJ-UHFFFAOYSA-N 2-[4-chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetic acid Chemical compound CC1=C(Cl)C(C(F)(F)F)=NN1CC(O)=O IZBZQUREHISXFJ-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 229960003109 daunorubicin hydrochloride Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229960000304 folic acid Drugs 0.000 description 2
- 235000019152 folic acid Nutrition 0.000 description 2
- 239000011724 folic acid Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- MLIWQXBKMZNZNF-KUHOPJCQSA-N (2e)-2,6-bis[(4-azidophenyl)methylidene]-4-methylcyclohexan-1-one Chemical compound O=C1\C(=C\C=2C=CC(=CC=2)N=[N+]=[N-])CC(C)CC1=CC1=CC=C(N=[N+]=[N-])C=C1 MLIWQXBKMZNZNF-KUHOPJCQSA-N 0.000 description 1
- GBKVTQSWZCBVSL-FHAQVOQBSA-N (2s,3s)-2-amino-3-methylpentanoic acid;hydrochloride Chemical compound Cl.CC[C@H](C)[C@H](N)C(O)=O GBKVTQSWZCBVSL-FHAQVOQBSA-N 0.000 description 1
- VFTRKSBEFQDZKX-UHFFFAOYSA-N 3,3'-diindolylmethane Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4NC=3)=CNC2=C1 VFTRKSBEFQDZKX-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- KCURWTAZOZXKSJ-JBMRGDGGSA-N 4-amino-1-[(2r,3s,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one;hydron;chloride Chemical compound Cl.O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 KCURWTAZOZXKSJ-JBMRGDGGSA-N 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000005749 Copper compound Substances 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical group O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 108700022034 Opsonin Proteins Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 230000006682 Warburg effect Effects 0.000 description 1
- JCABVIFDXFFRMT-DIPNUNPCSA-N [(2r)-1-[ethoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] octadec-9-enoate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC)OC(=O)CCCCCCCC=CCCCCCCCC JCABVIFDXFFRMT-DIPNUNPCSA-N 0.000 description 1
- XHCLAFWTIXFWPH-UHFFFAOYSA-N [O-2].[O-2].[O-2].[O-2].[O-2].[V+5].[V+5] Chemical compound [O-2].[O-2].[O-2].[O-2].[O-2].[V+5].[V+5] XHCLAFWTIXFWPH-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 150000001880 copper compounds Chemical class 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- RMKNCYHVESPYFD-UHFFFAOYSA-N decan-1-amine;hydrochloride Chemical compound [Cl-].CCCCCCCCCC[NH3+] RMKNCYHVESPYFD-UHFFFAOYSA-N 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- TWJAXIHBWPVMIR-UHFFFAOYSA-N diindolylmethane Natural products C1=CC=C2NC(CC=3NC4=CC=CC=C4C=3)=CC2=C1 TWJAXIHBWPVMIR-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 239000003269 fluorescent indicator Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 125000000524 functional group Chemical class 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 description 1
- PHFDTSRDEZEOHG-UHFFFAOYSA-N hydron;octan-1-amine;chloride Chemical compound Cl.CCCCCCCCN PHFDTSRDEZEOHG-UHFFFAOYSA-N 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940050526 hydroxyethylstarch Drugs 0.000 description 1
- 230000000899 immune system response Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000411 inducer Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 239000002159 nanocrystal Substances 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-M periodate Chemical compound [O-]I(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-M 0.000 description 1
- 230000010399 physical interaction Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(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- Chemical compound [Na+].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 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 229910001935 vanadium oxide Inorganic materials 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B1/00—Preparatory treatment of cellulose for making derivatives thereof, e.g. pre-treatment, pre-soaking, activation
- C08B1/08—Alkali cellulose
- C08B1/10—Apparatus for the preparation of alkali cellulose
- C08B1/12—Steeping devices
-
- 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
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- 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
- A61K47/6939—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 a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin
-
- 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
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B11/00—Preparation of cellulose ethers
- C08B11/02—Alkyl or cycloalkyl ethers
- C08B11/04—Alkyl or cycloalkyl ethers with substituted hydrocarbon radicals
- C08B11/10—Alkyl or cycloalkyl ethers with substituted hydrocarbon radicals substituted with acid radicals
- C08B11/12—Alkyl or cycloalkyl ethers with substituted hydrocarbon radicals substituted with acid radicals substituted with carboxylic radicals, e.g. carboxymethylcellulose [CMC]
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0021—Dextran, i.e. (alpha-1,4)-D-glucan; Derivatives thereof, e.g. Sephadex, i.e. crosslinked dextran
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/006—Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof
- C08B37/0063—Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan
- C08B37/0072—Hyaluronic acid, i.e. HA or hyaluronan; Derivatives thereof, e.g. crosslinked hyaluronic acid (hylan) or hyaluronates
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
- C08L1/08—Cellulose derivatives
- C08L1/26—Cellulose ethers
- C08L1/28—Alkyl ethers
- C08L1/286—Alkyl ethers substituted with acid radicals, e.g. carboxymethyl cellulose [CMC]
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/02—Dextran; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82B—NANOSTRUCTURES FORMED BY MANIPULATION OF INDIVIDUAL ATOMS, MOLECULES, OR LIMITED COLLECTIONS OF ATOMS OR MOLECULES AS DISCRETE UNITS; MANUFACTURE OR TREATMENT THEREOF
- B82B1/00—Nanostructures formed by manipulation of individual atoms or molecules, or limited collections of atoms or molecules as discrete units
Abstract
Description
分子量70kDaのデキストランを過ヨウ素酸ナトリウムで酸化して、約5%のグルコース環を酸化し、精製した。これを実施するために、デキストラン水溶液を調製し、過ヨウ素酸ナトリウムをそれに添加した。この反応の化学量論は、酸化条件、分子量、及び多くの場合、デキストランの源によって決まり、1モルの酸化グルコース当たり1〜2モルの過ヨウ素酸塩に相当し(2つのアルデヒド基が形成される)、これは、実験的に確認されなければならない。デキストラン酸化のプロセスを、黒いガラス製の容器中、室温で1時間、実施した。その後、この溶液を中和し、蒸留水に対する透析により精製し、その後、真空中で水を揮散させた。アルデヒド基の数を既知のヒドロキシルアミン滴定法により決定した。該デキストランの5%蒸留水溶液を調製した。その後、使用量の酸化デキストラン中のアルデヒド基のモル数に基づく15mol%の塩酸ダウノルビシンを添加した。この溶液を30℃で20分間撹拌した。その後、5%塩酸ドデシルアミン水溶液を、使用量の酸化デキストラン中のアルデヒド基の初期のモル数に基づく85mol%で添加し、温度を35℃に上昇させ、反応を60分間継続させた。実行中の反応は、反応環境のpHを低下させる。その後、5%NaOH水溶液を添加することにより、pHの上昇を開始させた。30分でpHをpH9に上昇させるように、添加を実施した。pH=9に達した後、反応を更に30分間継続させた。その後、アラニンを、使用量の酸化デキストラン中のアルデヒド基の初期のモル数に基づく15mol%で添加して、全ての未反応アルデヒド基を結合させた。15分間撹拌した後、この溶液を5%塩酸でpH=7に中和し、24時間の透析により精製した。その後、(酸化デキストランの初期重量に基づく)20重量%の純粋な非酸化デキストランを抗凍結剤として添加し、溶液を凍結乾燥させた。粉末を水に再懸濁させると、ナノ粒子の懸濁液が得られた。得られたナノ粒子の直径の分布を、図1に示すMalvern Zeta Sizer装置で測定した。405nmレーザーを備えたNanoSight装置で行なわれた測定により、わずかにより小さい平均粒径及びより狭い直径分布が明らかになった。
分子量40kDaのデキストランを過ヨウ素酸ナトリウムで酸化して、約20%のグルコース環を酸化し、精製した。そのようなデキストランの10%蒸留水溶液を調製した。その後、使用量の酸化デキストラン中のアルデヒド基のモル数に基づく20mol%の塩酸ドキソルビシンを添加した。この溶液を30℃で20分間撹拌した。その後、5%塩酸オクチルアミン水溶液を、使用量の酸化デキストラン中のアルデヒド基の初期のモル数に基づく80mol%で添加し、温度を40℃に上昇させ、反応を60分間継続させた。実行中の反応は、pHの低下を引き起こす。その後、5%NaOH水溶液を添加することにより、pHの上昇を開始させた。30分でpHをpH8に上昇させるように、添加を実施した。pH=8に達した後、反応を更に30分間継続させた。その後、アラニンを、使用量の酸化デキストラン中のアルデヒド基の初期のモル数に基づく10mol%で添加した。15分間撹拌した後、この溶液を5%塩酸でpH=7に中和し、NaBH3CNをアルデヒド基の初期量に基づく10mol%過剰で添加した。その後、反応を12時間実施した。この溶液を中和し、48時間の徹底的な透析により精製し、その後、デキストランをデキストランの初期重量に基づく50重量%で添加し、溶液を凍結乾燥させた。水に再懸濁させた後、得られたナノ粒子の直径の分布を、405nmレーザーを備えたNanoSight装置で測定し、図2に示した。
分子量約100kDa及び酸化数5%のカルボキシメチルセルロースの4%水溶液を調製し、pHをpH5に調整した。その後、9−アミノアクリジンを、その塩酸塩水溶液として、使用されたセルロース誘導体のアルデヒド基の初期量に基づく50mol%で添加した。その後、水性オクチルアミンをアルデヒド基の初期のモル数に基づく55mol%で添加した。反応を40℃で1時間実施した。その後、15分でpHをpH9に上昇させることにより、この溶液を中和し、30分間放置し、透析した。150nmの平均直径の蛍光ナノ粒子が得られた。
分子量70kDaのデキストランを過ヨウ素酸ナトリウムで酸化して、約15%のグルコース環を酸化し、精製した。そのようなデキストランの10%蒸留水溶液を調製した。その後、使用量の酸化デキストラン中のアルデヒド基のモル数に基づく25mol%の塩酸ドキソルビシンを添加した。この溶液を35℃で20分間撹拌した。その後、葉酸をアルデヒド基の初期の量に基づく5mol%で添加して、腫瘍細胞に対するナノ粒子の親和性を増強させた。15分後、5%塩酸イソロイシン水溶液を、使用量の酸化デキストラン中のアルデヒド基の初期のモル数に基づく80mol%で添加し、温度を40℃に上昇させ、反応を60分間実施した。その後、5%NaOH水溶液を添加することにより、pHの上昇を開始させた。30分でpHをpH9.5に上昇させるように、添加を実施した。反応を更に30分間継続させた。その後、この溶液を中和し、24時間の透析により精製した。得られたナノ粒子の平均直径は、140nmであった。
カルボキシメチルセルロースナトリウム塩を、水溶液中、テトラ−スルホ鉄−フタロシアニン触媒の存在下、過酸化水素で酸化した[非特許文献7]。このプロセスを40℃で12時間実施し、その後、生成物を、濾過、次いで、透析により精製した。得られたアルデヒドカルボキシメチルセルロース誘導体中のアルデヒド基の量を、既知のヒドロキシルアミン滴定法により決定した。得られた誘導体の5%蒸留水溶液を調製した。その後、使用量の酸化デキストラン中のアルデヒド基のモル数に基づく10mol%の塩酸ドキソルビシンを添加した。この溶液を30℃で20分間撹拌した。その後、5%塩酸ドデシルアミン水溶液を、使用量の酸化デキストラン中のアルデヒド基の初期のモル数に基づく90mol%で添加し、温度を35℃に上昇させ、反応を60分間継続させた。その後、5%NaOH水溶液を添加することにより、pHの上昇を開始させた。30分でpHをpH9に上昇させるように、添加を実施した。pH=9に達した後、反応を更に30分間継続させた。その後、アラニンを、使用量の酸化デキストラン中のアルデヒド基の初期のモル数に基づく30mol%で添加して、全ての未反応アルデヒド基を結合させた。15分間撹拌した後、この溶液を5%塩酸でpH=7に中和し、24時間の透析により精製した。Malvern Zeta Sizer装置で測定したときの、得られたナノ粒子の平均直径は、110nmであった。
1%ヒアルロン酸ナトリウム塩水溶液を調製し、実施例1と同様に、5%の酸化度にまで過ヨウ素酸ナトリウムで酸化した。pHをpH5に調整し、塩酸ダウノルビシン及び塩酸シタラビンを、酸化ヒアルロン酸の全アルデヒド基の10mol%を含む各々の薬物に対して添加し、反応を30℃で15分間実施した。その後、塩酸デシルアミン水溶液を、アルデヒド基の初期のモル数に基づく85mol%で添加した。反応を40℃で1時間実施した。その後、20分以内にpHをpH9に上昇させ、この溶液を中和し、透析した。作用機序の異なる2種の薬物を含む多糖ナノ粒子の水懸濁液が得られた。
Claims (19)
- アルデヒド基を生成させ、アルデヒド基と反応するアミノ基又はR−NH2結合を有するその他の基を有する化合物を付加するその特異的部分酸化により、多糖及びその誘導体からナノ粒子を調製する方法であって、該多糖又はその誘導体を、糖環の0.1%〜80%の酸化度が得られるまで、既知の方法により酸化して、アルデヒド基を得、次いで、該アルデヒド基の結合後、4〜20個の炭素原子を含有する脂肪族又は芳香族有機アミン、4〜20個の炭素原子を含有する脂肪族及び芳香族有機酸のアミド及びヒドラジド、疎水性アミノ酸、ホスファチジルエタノールアミン、並びに少なくとも1つのアミノ、アミド、又はヒドラジド基を含有する少なくとも1つの活性物質:を含む群から選択される、疎水性を示す少なくとも1つのナノ粒子形成剤を、水又は水と有機溶媒との混合物中の酸化された多糖の溶液に添加し、反応を、該溶液の1〜9のpHで、10〜100℃の温度で実施することを特徴とし、ここで、アミノ基対アルデヒド基の総モル比が20〜0.5である、方法。
- 前記ナノ粒子形成剤が前記活性物質と同時に添加されることを特徴とする、請求項1に記載の方法。
- 前記ナノ粒子形成剤が前記活性物質を添加した後に添加されることを特徴とする、請求項1に記載の方法。
- 前記ナノ粒子形成剤が、ブチルアミン、ペンチルアミン、ヘキシルアミン、オクチルアミン、デシルアミン、ドデシルアミン、テトラデシルアミン、ヘキサデシルアミン、シクロヘキシルアミン、ベンジルアミン、エチルフェニルアミン、スフィンゴシン、オレイン酸アミド、パルミチン酸アミド、ステアリン酸ヒドラジド、パルミチン酸ヒドラジド、オレイン酸ヒドラジド、ロイシン、イソロイシン、バリン、メチオニン、アラニン、フェニルアラニン、セファリン:を含む群から選択されることを特徴とする、請求項1に記載の方法。
- 前記活性物質として、アミノ、アミド、もしくはヒドラジド基を含む薬物、又はカルボキシ基がアミドもしくはヒドラジドに修飾されている誘導薬物、遺伝子治療に好適なRNAもしくはDNA断片、又はこれらの誘導体、プレーン色素及び蛍光色素が使用されることを特徴とする、請求項1に記載の方法。
- 前記活性物質が、ダウノルビシン、ドキソルビシン、アミノアクリジン及びその誘導体、シスプラチン及びその誘導体、メトトレキセート、シタラビン、ゲムシタビン、ダプソン、アシクロビル、アジドチミジン、5−フルオロウラシル、メルカプトプリン、イマチニブ、スニチニブ、ブレオマイシン、アクチノマイシン、マイトマイシン、ダクチノマイシン、メルファラン、テモゾロミド、セレコキシブ、ネララビン、クラドリビン、イソニアジド、9−アミノアクリジン及び他のアクリジン色素、DAPI、ローダミン及びその誘導体、ニュートラルレッド、トリパンブルー:を含む群から選択されることを特徴とする、請求項1又は5に記載の方法。
- 前記形成剤と前記活性物質の両方が、反応液中に、易溶性塩の形態で添加されることを特徴とする、請求項1に記載の方法。
- 塩酸塩、硝酸塩、又は硫酸塩が、塩として使用されることを特徴とする、請求項7に記載の方法。
- デキストラン、デンプン及びその誘導体、アミロース及びその誘導体、セルロース誘導体、グリコーゲン、ヒアルロン酸、ヘパリン、アルギン酸、カラギーンが、多糖として使用されることを特徴とする、請求項1に記載の方法。
- 水/DMSO、水/アセトニトリル、水/エーテル溶媒混合物中で実施されることを特徴とする、請求項1に記載の方法。
- 前記酸化が、多糖中の糖環の0.1%〜80%の酸化度が得られるまで実施されることを特徴とする、請求項1に記載の方法。
- 前記酸化が、過ヨウ素酸イオンを含む酸化剤、酸化数4の鉛の塩、酸化数2の銅の化合物、又は好適な触媒の存在下で酸化された水の存在下で実施されることを特徴とする、請求項1に記載の方法。
- 前記反応が終了した後、形成された結合の還元が実施されることを特徴とする、請求項1に記載の方法。
- 前記還元が、NaBH4又はNaBH3CNにより、水溶液中で実施されることを特徴とする、請求項13に記載の方法。
- 水性ナノ粒子懸濁液が、透析、沈殿、遠心分離により精製されるか、又はそれが直接使用されることを特徴とする、請求項1に記載の方法。
- 得られたナノ粒子が、酸化された多糖のアルデヒド基とペプチドアミノ基との反応によっても、抗体、ペプチド、又はタンパク質で修飾されることを特徴とする、請求項1に記載の方法。
- 前記得られたナノ粒子の溶液が凍結乾燥されることを特徴とする、請求項1に記載の方法。
- 凍結乾燥が凍結防止物質を添加して実施されることを特徴とする、請求項17に記載の方法。
- 抗凍結剤が未修飾多糖であることを特徴とする、請求項18に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PL398450A PL221351B1 (pl) | 2012-03-14 | 2012-03-14 | Sposób otrzymywania nanocząstek polisacharydowych |
PLPL398450 | 2012-03-14 | ||
PCT/PL2013/000030 WO2013137755A1 (en) | 2012-03-14 | 2013-03-12 | Process for the preparation of polysaccharide nanoparticles |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2015514059A true JP2015514059A (ja) | 2015-05-18 |
JP6470169B2 JP6470169B2 (ja) | 2019-02-13 |
Family
ID=48014274
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015500386A Active JP6470169B2 (ja) | 2012-03-14 | 2013-03-12 | 多糖ナノ粒子の調製方法 |
Country Status (14)
Country | Link |
---|---|
US (1) | US10258579B2 (ja) |
EP (1) | EP2825563B1 (ja) |
JP (1) | JP6470169B2 (ja) |
CN (1) | CN104169305B (ja) |
AU (1) | AU2013232850B2 (ja) |
BR (1) | BR112014022767B1 (ja) |
CA (1) | CA2866682C (ja) |
ES (1) | ES2780387T3 (ja) |
IL (1) | IL234572A (ja) |
IN (1) | IN2014MN01651A (ja) |
MX (1) | MX369114B (ja) |
PL (1) | PL221351B1 (ja) |
RU (1) | RU2632019C2 (ja) |
WO (1) | WO2013137755A1 (ja) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016093352A1 (ja) * | 2014-12-12 | 2016-06-16 | 日本化薬株式会社 | 核酸代謝拮抗剤が結合した多分岐化合物 |
CA3032635A1 (en) * | 2016-08-01 | 2018-02-08 | Hppe, Llc | Biopolymers for fugitive dust control |
US10736964B2 (en) * | 2017-05-01 | 2020-08-11 | China Medical University | Immunomagnetic nanocapsule and kit for treating cancer |
CN107446054B (zh) * | 2017-08-11 | 2021-05-18 | 武汉理工大学 | 一种生物质基纳米粒子及其制备方法和应用 |
PL424773A1 (pl) * | 2018-03-06 | 2019-09-09 | Nanovelos Spółka Akcyjna | Enkapsulowana polisacharydem antracyklina do zastosowania w leczeniu nowotworów |
CN108676181B (zh) * | 2018-05-30 | 2022-05-17 | 江西师范大学 | 通过二醛基纤维素制备纤维素纳米颗粒的方法 |
CN108553448A (zh) * | 2018-05-30 | 2018-09-21 | 江西师范大学 | 一种pH响应的药物缓释纤维素纳米颗粒的制备方法 |
PL240772B1 (pl) | 2018-06-11 | 2022-06-06 | Nanothea Spolka Akcyjna | Sposób wytwarzania nanocząstek polimerowych chelatujących izotopy promieniotwórcze do zastosowania w diagnostyce i terapii |
CN112353781B (zh) * | 2020-11-12 | 2022-08-19 | 云南开放大学 | 一种药物载体空心纳米球的制备方法 |
CN112516310B (zh) * | 2020-12-11 | 2022-11-29 | 武汉理工大学 | 一种肿瘤酸环境响应的纳米前药的制备方法及其应用 |
CN112830979A (zh) * | 2021-01-15 | 2021-05-25 | 江南大学 | 一种改性黄原胶及其制备方法与应用 |
CN113800501B (zh) * | 2021-10-08 | 2023-04-18 | 山西大学 | 一种用于检测pH和精氨酸的橙红色荧光碳点的制备方法及其应用 |
WO2023092208A1 (pt) * | 2021-11-25 | 2023-06-01 | Universidade Estadual De Campinas | Processo de obtenção de solução polimérica injetável fotoreticulável, solução polimérica injetável fotoreticulável e seus usos |
CN115463262A (zh) * | 2022-08-11 | 2022-12-13 | 南方医科大学第五附属医院 | 一种水凝胶复合修复补片及其制备方法与应用 |
Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS61222531A (ja) * | 1985-02-28 | 1986-10-03 | テクニコン・インストウルメンツ・コーポレイシヨン | 試薬被覆粒子の凍結乾燥方法 |
JPS62221637A (ja) * | 1986-03-24 | 1987-09-29 | Green Cross Corp:The | 制癌剤−抗体複合体の製造方法 |
JPS62283101A (ja) * | 1986-05-30 | 1987-12-09 | Green Cross Corp:The | 制癌作用物質複合体の製造方法 |
JPS63264427A (ja) * | 1986-12-17 | 1988-11-01 | Green Cross Corp:The | 制癌作用物質複合体 |
JPS63503138A (ja) * | 1986-02-25 | 1988-11-17 | センタ−、フォア、モレキュラ−、メディシン、アンド、イミュノロジ− | 診断および治療用抗体複合体 |
JPH01190636A (ja) * | 1988-01-22 | 1989-07-31 | Green Cross Corp:The | 制癌作用物質複合体 |
JP2002530321A (ja) * | 1998-11-20 | 2002-09-17 | アールティーピー・ファーマ・インコーポレーテッド | 分散し得るリン脂質で安定化されたミクロ粒子 |
JP2003505473A (ja) * | 1999-07-23 | 2003-02-12 | ポリジーン リミティッド | アニオン性高分子の送達のための生分解性ポリカチオン組成物 |
JP2005535604A (ja) * | 2002-06-03 | 2005-11-24 | アルニス バイオサイエンシーズ, インコーポレイテッド | 治療剤を含むポリマーナノ物品 |
JP2008542295A (ja) * | 2005-05-27 | 2008-11-27 | ロイヤー バイオメディカル, インク. | 生体再吸収性ポリマーマトリックス、ならびにその作製および使用方法 |
JP2009508938A (ja) * | 2005-09-22 | 2009-03-05 | ハダシット メディカル リサーチ サーヴィスィズ アンド ディベロップメント リミテッド | 治療上活性な化合物の結合体 |
WO2010080557A1 (en) * | 2008-12-17 | 2010-07-15 | New World Pharmaceuticals, Llc | Sustained release of nutrients in vivo |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SU825542A1 (ru) * | 1979-04-04 | 1981-04-30 | Inst Orch Chimii Aka | Способ получения n-производных полисахаридов 1 |
US4452773A (en) * | 1982-04-05 | 1984-06-05 | Canadian Patents And Development Limited | Magnetic iron-dextran microspheres |
EP0999222A1 (en) | 1998-11-02 | 2000-05-10 | Nederlandse Organisatie Voor Toegepast-Natuurwetenschappelijk Onderzoek Tno | Carbohydrate oxidation products |
CA2412582A1 (en) | 2000-06-29 | 2002-01-03 | Daiichi Pharmaceutical Co., Ltd. | Dds compound and process for the preparation thereof |
DE10129369C1 (de) * | 2001-06-21 | 2003-03-06 | Fresenius Kabi De Gmbh | Wasserlösliches, einen Aminozucker aufweisendes Antibiotikum in Form eines Pol ysaccharid-Konjugats |
TWI313609B (en) | 2001-08-21 | 2009-08-21 | Mitsubishi Tanabe Pharma Corp | Pharmaceutical composition for inhibiting the metastasis or preventing the recurrence of malignant tumor |
DE10209821A1 (de) * | 2002-03-06 | 2003-09-25 | Biotechnologie Ges Mittelhesse | Kopplung von Proteinen an ein modifiziertes Polysaccharid |
KR100578382B1 (ko) * | 2004-07-16 | 2006-05-11 | 나재운 | 항암제의 전달체용 수용성 키토산 나노입자 및 그 제조방법 |
GB0502095D0 (en) | 2005-02-01 | 2005-03-09 | Chiron Srl | Conjugation of streptococcal capsular saccharides |
EP1937304A2 (en) | 2005-08-24 | 2008-07-02 | Novartis Vaccines and Diagnostics S.r.l. | Zwitterionization of capsular saccharides |
WO2007029898A1 (en) * | 2005-09-09 | 2007-03-15 | Jae-Woon Nah | Water soluble chitosan nanoparticle for delivering an anticancer agent and preparing method thereof |
CN105833337B (zh) * | 2008-11-19 | 2020-01-21 | 阿克塔马克斯手术器材有限责任公司 | 纤维组织封合剂及其使用方法 |
CZ302503B6 (cs) * | 2009-12-11 | 2011-06-22 | Contipro C A.S. | Zpusob prípravy derivátu kyseliny hyaluronové oxidovaného v poloze 6 glukosaminové cásti polysacharidu selektivne na aldehyd a zpusob jeho modifikace |
WO2012004007A1 (en) * | 2010-07-09 | 2012-01-12 | Fresenius Kabi Deutschland Gmbh | Conjugates comprising hydroxyalkyl starch and a cytotoxic agent and process for their preparation |
-
2012
- 2012-03-14 PL PL398450A patent/PL221351B1/pl unknown
-
2013
- 2013-03-12 CN CN201380014214.8A patent/CN104169305B/zh active Active
- 2013-03-12 IN IN1651MUN2014 patent/IN2014MN01651A/en unknown
- 2013-03-12 RU RU2014133962A patent/RU2632019C2/ru active
- 2013-03-12 EP EP13712947.4A patent/EP2825563B1/en active Active
- 2013-03-12 WO PCT/PL2013/000030 patent/WO2013137755A1/en active Application Filing
- 2013-03-12 BR BR112014022767-5A patent/BR112014022767B1/pt active IP Right Grant
- 2013-03-12 MX MX2014010979A patent/MX369114B/es active IP Right Grant
- 2013-03-12 JP JP2015500386A patent/JP6470169B2/ja active Active
- 2013-03-12 AU AU2013232850A patent/AU2013232850B2/en active Active
- 2013-03-12 ES ES13712947T patent/ES2780387T3/es active Active
- 2013-03-12 CA CA2866682A patent/CA2866682C/en active Active
-
2014
- 2014-09-10 IL IL234572A patent/IL234572A/en active IP Right Grant
- 2014-09-12 US US14/485,309 patent/US10258579B2/en active Active
Patent Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS61222531A (ja) * | 1985-02-28 | 1986-10-03 | テクニコン・インストウルメンツ・コーポレイシヨン | 試薬被覆粒子の凍結乾燥方法 |
JPS63503138A (ja) * | 1986-02-25 | 1988-11-17 | センタ−、フォア、モレキュラ−、メディシン、アンド、イミュノロジ− | 診断および治療用抗体複合体 |
JPS62221637A (ja) * | 1986-03-24 | 1987-09-29 | Green Cross Corp:The | 制癌剤−抗体複合体の製造方法 |
JPS62283101A (ja) * | 1986-05-30 | 1987-12-09 | Green Cross Corp:The | 制癌作用物質複合体の製造方法 |
JPS63264427A (ja) * | 1986-12-17 | 1988-11-01 | Green Cross Corp:The | 制癌作用物質複合体 |
JPH01190636A (ja) * | 1988-01-22 | 1989-07-31 | Green Cross Corp:The | 制癌作用物質複合体 |
JP2002530321A (ja) * | 1998-11-20 | 2002-09-17 | アールティーピー・ファーマ・インコーポレーテッド | 分散し得るリン脂質で安定化されたミクロ粒子 |
JP2003505473A (ja) * | 1999-07-23 | 2003-02-12 | ポリジーン リミティッド | アニオン性高分子の送達のための生分解性ポリカチオン組成物 |
JP2005535604A (ja) * | 2002-06-03 | 2005-11-24 | アルニス バイオサイエンシーズ, インコーポレイテッド | 治療剤を含むポリマーナノ物品 |
JP2008542295A (ja) * | 2005-05-27 | 2008-11-27 | ロイヤー バイオメディカル, インク. | 生体再吸収性ポリマーマトリックス、ならびにその作製および使用方法 |
JP2009508938A (ja) * | 2005-09-22 | 2009-03-05 | ハダシット メディカル リサーチ サーヴィスィズ アンド ディベロップメント リミテッド | 治療上活性な化合物の結合体 |
WO2010080557A1 (en) * | 2008-12-17 | 2010-07-15 | New World Pharmaceuticals, Llc | Sustained release of nutrients in vivo |
Also Published As
Publication number | Publication date |
---|---|
CN104169305B (zh) | 2016-07-27 |
BR112014022767B1 (pt) | 2021-08-31 |
PL398450A1 (pl) | 2013-09-16 |
AU2013232850A1 (en) | 2014-09-11 |
US10258579B2 (en) | 2019-04-16 |
EP2825563A1 (en) | 2015-01-21 |
US20150072946A1 (en) | 2015-03-12 |
PL221351B1 (pl) | 2016-03-31 |
MX2014010979A (es) | 2015-02-24 |
AU2013232850B2 (en) | 2016-01-07 |
MX369114B (es) | 2019-10-29 |
CN104169305A (zh) | 2014-11-26 |
JP6470169B2 (ja) | 2019-02-13 |
RU2632019C2 (ru) | 2017-10-02 |
ES2780387T3 (es) | 2020-08-25 |
RU2014133962A (ru) | 2016-03-20 |
WO2013137755A1 (en) | 2013-09-19 |
IN2014MN01651A (ja) | 2015-05-29 |
BR112014022767A2 (ja) | 2017-10-03 |
IL234572A (en) | 2017-01-31 |
CA2866682A1 (en) | 2013-09-19 |
EP2825563B1 (en) | 2020-02-05 |
CA2866682C (en) | 2016-05-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6470169B2 (ja) | 多糖ナノ粒子の調製方法 | |
Pooresmaeil et al. | Advances in development of the dendrimers having natural saccharides in their structure for efficient and controlled drug delivery applications | |
Debele et al. | Polysaccharide based nanogels in the drug delivery system: Application as the carrier of pharmaceutical agents | |
Singh et al. | Pullulan and pullulan derivatives as promising biomolecules for drug and gene targeting | |
Goodarzi et al. | A review of polysaccharide cytotoxic drug conjugates for cancer therapy | |
Saravanakumar et al. | Polysaccharide-based nanoparticles: a versatile platform for drug delivery and biomedical imaging | |
Cai et al. | Reduction-and pH-sensitive hyaluronan nanoparticles for delivery of iridium (III) anticancer drugs | |
Youn et al. | Multifunctional nano-sized fullerenes for advanced tumor therapy | |
Kashkouli et al. | Synthesis and characterization of aminotetrazole-functionalized magnetic chitosan nanocomposite as a novel nanocarrier for targeted gene delivery | |
Kang et al. | pH-sensitive fluorescent hyaluronic acid nanogels for tumor-targeting and controlled delivery of doxorubicin and nitric oxide | |
Della Sala et al. | Advances in Hyaluronic‐Acid‐Based (Nano) Devices for Cancer Therapy | |
Liu et al. | Cell membrane-inspired polymeric micelles as carriers for drug delivery | |
Jang et al. | Hyaluronic acid-siRNA conjugate/reducible polyethylenimine complexes for targeted siRNA delivery | |
Ghassami et al. | Redox sensitive polysaccharide based nanoparticles for improved cancer treatment: a comprehensive review | |
Ebani et al. | Carboxymethyl chitosan/ionic liquid imidazolium-based nanoparticles as nanocarriers for zinc phthalocyanine and its photodynamic activity | |
Padhi et al. | Chitosan-based drug delivery systems in cancer therapeutics | |
WO2008007932A1 (en) | Chitosan complex containing ph sensitive imidazole group and preparation method thereof | |
Feng et al. | Natural Hydrogels Applied in Photodynamic Therapy | |
US9119391B1 (en) | Polymer coated ceria nanoparticles for selective cytoprotection | |
AU2022334942A1 (en) | Diblock polymer | |
Nigam et al. | Aptamer functionalized multifunctional fluorescent nanotheranostic platform for pancreatic cancer | |
KR101323102B1 (ko) | 글리콜키토산-담즙산 복합체에 항암제가 봉입된 나노입자 및 그 제조방법 | |
Gomes et al. | Polysaccharide-based nanoparticles for cancer therapy | |
Deka et al. | Design, fabrication and evaluation of amphiphilic hyaluronic acid conjugates as efficient carriers of 6‐thioguanine for in vitro anticancer drug delivery applications | |
Maghsoudnia et al. | Hyaluronic Acid in Drug Delivery |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150825 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20160520 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160524 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160817 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161124 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170502 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170719 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171031 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20180206 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180606 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20180608 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20180629 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180904 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181015 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20181211 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181227 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190108 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190117 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6470169 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |