EA028655B1 - Сульфатированный полисахарид полигулоновой кислоты или фармацевтическая соль, способ получения и применение - Google Patents
Сульфатированный полисахарид полигулоновой кислоты или фармацевтическая соль, способ получения и применение Download PDFInfo
- Publication number
- EA028655B1 EA028655B1 EA201690123A EA201690123A EA028655B1 EA 028655 B1 EA028655 B1 EA 028655B1 EA 201690123 A EA201690123 A EA 201690123A EA 201690123 A EA201690123 A EA 201690123A EA 028655 B1 EA028655 B1 EA 028655B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- inhibitors
- pharmaceutically acceptable
- acid sulfate
- polygulonic acid
- cancer
- Prior art date
Links
- 239000002253 acid Substances 0.000 title claims abstract description 76
- 150000003839 salts Chemical class 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 229920001282 polysaccharide Polymers 0.000 title description 10
- 239000005017 polysaccharide Substances 0.000 title description 10
- 150000004676 glycans Chemical class 0.000 title description 9
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims abstract description 65
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 44
- 239000003112 inhibitor Substances 0.000 claims abstract description 22
- 102000007469 Actins Human genes 0.000 claims abstract description 18
- 108010085238 Actins Proteins 0.000 claims abstract description 18
- 108010037536 heparanase Proteins 0.000 claims abstract description 14
- 102100024025 Heparanase Human genes 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 12
- 230000029115 microtubule polymerization Effects 0.000 claims abstract description 6
- 230000002776 aggregation Effects 0.000 claims abstract description 5
- 238000004220 aggregation Methods 0.000 claims abstract description 5
- 239000004037 angiogenesis inhibitor Substances 0.000 claims abstract description 5
- 229940121369 angiogenesis inhibitor Drugs 0.000 claims abstract description 5
- 239000002257 antimetastatic agent Substances 0.000 claims abstract description 4
- 239000002532 enzyme inhibitor Substances 0.000 claims abstract description 3
- 206010027476 Metastases Diseases 0.000 claims description 28
- 230000002401 inhibitory effect Effects 0.000 claims description 23
- 230000009401 metastasis Effects 0.000 claims description 21
- 206010006187 Breast cancer Diseases 0.000 claims description 19
- 208000026310 Breast neoplasm Diseases 0.000 claims description 19
- 230000012010 growth Effects 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 239000003638 chemical reducing agent Substances 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 239000011593 sulfur Substances 0.000 claims description 7
- 201000001441 melanoma Diseases 0.000 claims description 6
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical group CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 4
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000012279 sodium borohydride Substances 0.000 claims description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 230000001180 sulfating effect Effects 0.000 claims description 3
- 230000019635 sulfation Effects 0.000 claims description 3
- 238000005670 sulfation reaction Methods 0.000 claims description 3
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 229910000652 nickel hydride Inorganic materials 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 206010038038 rectal cancer Diseases 0.000 claims description 2
- 201000001275 rectum cancer Diseases 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 238000006277 sulfonation reaction Methods 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 230000004614 tumor growth Effects 0.000 abstract description 10
- 239000003966 growth inhibitor Substances 0.000 abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- 239000000243 solution Substances 0.000 description 26
- 230000000694 effects Effects 0.000 description 24
- 230000005764 inhibitory process Effects 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 19
- 241000699670 Mus sp. Species 0.000 description 13
- 210000004072 lung Anatomy 0.000 description 13
- 235000000346 sugar Nutrition 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 10
- 239000012528 membrane Substances 0.000 description 10
- 102000015693 Actin Depolymerizing Factors Human genes 0.000 description 9
- 108010038798 Actin Depolymerizing Factors Proteins 0.000 description 9
- 206010027458 Metastases to lung Diseases 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 235000013601 eggs Nutrition 0.000 description 9
- 210000004379 membrane Anatomy 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
- 230000033115 angiogenesis Effects 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 150000001720 carbohydrates Chemical class 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 229920002307 Dextran Polymers 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 238000011081 inoculation Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 241000287828 Gallus gallus Species 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 102000004243 Tubulin Human genes 0.000 description 4
- 108090000704 Tubulin Proteins 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 230000000259 anti-tumor effect Effects 0.000 description 4
- 201000011510 cancer Diseases 0.000 description 4
- 210000004671 cell-free system Anatomy 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000010253 intravenous injection Methods 0.000 description 4
- 210000001161 mammalian embryo Anatomy 0.000 description 4
- 230000005012 migration Effects 0.000 description 4
- 238000013508 migration Methods 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 150000004044 tetrasaccharides Chemical class 0.000 description 4
- 102000002322 Egg Proteins Human genes 0.000 description 3
- 108010000912 Egg Proteins Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 229960004679 doxorubicin Drugs 0.000 description 3
- 210000003278 egg shell Anatomy 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 238000010186 staining Methods 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 239000011345 viscous material Substances 0.000 description 3
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- FNEHAOQZWPHONV-UHFFFAOYSA-N 9h-carbazole;sulfuric acid Chemical compound OS(O)(=O)=O.C1=CC=C2C3=CC=CC=C3NC2=C1 FNEHAOQZWPHONV-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229940122588 Heparanase inhibitor Drugs 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 238000004566 IR spectroscopy Methods 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 229940009456 adriamycin Drugs 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- OOULUYZFLXDWDQ-UHFFFAOYSA-L barium perchlorate Chemical compound [Ba+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O OOULUYZFLXDWDQ-UHFFFAOYSA-L 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000002485 combustion reaction Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 244000144977 poultry Species 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- MQLACMBJVPINKE-UHFFFAOYSA-N 10-[(3-hydroxy-4-methoxyphenyl)methylidene]anthracen-9-one Chemical compound C1=C(O)C(OC)=CC=C1C=C1C2=CC=CC=C2C(=O)C2=CC=CC=C21 MQLACMBJVPINKE-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- VVLAIYIMMFWRFW-UHFFFAOYSA-N 2-hydroxyethylazanium;acetate Chemical compound CC(O)=O.NCCO VVLAIYIMMFWRFW-UHFFFAOYSA-N 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 101100328895 Caenorhabditis elegans rol-8 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000222356 Coriolus Species 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 102000003668 Destrin Human genes 0.000 description 1
- 108090000082 Destrin Proteins 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108090001064 Gelsolin Proteins 0.000 description 1
- 229920002971 Heparan sulfate Polymers 0.000 description 1
- 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 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 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 description 1
- IAJILQKETJEXLJ-SQOUGZDYSA-N L-guluronic acid Chemical group O=C[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O IAJILQKETJEXLJ-SQOUGZDYSA-N 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- -1 Ropa polysaccharides Chemical class 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 210000004712 air sac Anatomy 0.000 description 1
- RGCKGOZRHPZPFP-UHFFFAOYSA-N alizarin Chemical compound C1=CC=C2C(=O)C3=C(O)C(O)=CC=C3C(=O)C2=C1 RGCKGOZRHPZPFP-UHFFFAOYSA-N 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000012496 blank sample Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000033383 cell-cell recognition Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 210000003711 chorioallantoic membrane Anatomy 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000011532 immunohistochemical staining Methods 0.000 description 1
- 238000003364 immunohistochemistry Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000001725 pyrenyl group Chemical group 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/737—Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C08B37/0084—Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Polymers & Plastics (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Materials Engineering (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Gastroenterology & Hepatology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310275323.7 | 2013-07-02 | ||
| CN201310275323.7A CN104277130A (zh) | 2013-07-02 | 2013-07-02 | 一种硫酸酯化聚古洛糖酸多糖或其可药用盐及其制备方法和用途 |
| PCT/CN2014/081472 WO2015000411A1 (zh) | 2013-07-02 | 2014-07-02 | 一种硫酸酯化聚古洛糖酸多糖或其可药用盐及其制备方法和用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201690123A1 EA201690123A1 (ru) | 2016-07-29 |
| EA028655B1 true EA028655B1 (ru) | 2017-12-29 |
Family
ID=52143111
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201690123A EA028655B1 (ru) | 2013-07-02 | 2014-07-02 | Сульфатированный полисахарид полигулоновой кислоты или фармацевтическая соль, способ получения и применение |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US10058566B2 (enExample) |
| EP (1) | EP3018147B1 (enExample) |
| JP (2) | JP6757249B2 (enExample) |
| KR (1) | KR102258569B1 (enExample) |
| CN (2) | CN104277130A (enExample) |
| AU (1) | AU2014286711B2 (enExample) |
| BR (1) | BR112015032849B1 (enExample) |
| CA (1) | CA2916749C (enExample) |
| DK (1) | DK3018147T3 (enExample) |
| EA (1) | EA028655B1 (enExample) |
| ES (1) | ES2674976T3 (enExample) |
| HU (1) | HUE038981T2 (enExample) |
| MX (1) | MX373099B (enExample) |
| PL (1) | PL3018147T3 (enExample) |
| PT (1) | PT3018147T (enExample) |
| SG (1) | SG11201510717SA (enExample) |
| TR (1) | TR201809674T4 (enExample) |
| WO (1) | WO2015000411A1 (enExample) |
| ZA (1) | ZA201509353B (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104277130A (zh) * | 2013-07-02 | 2015-01-14 | 中国科学院上海药物研究所 | 一种硫酸酯化聚古洛糖酸多糖或其可药用盐及其制备方法和用途 |
| CN107904240A (zh) * | 2017-12-04 | 2018-04-13 | 辽东学院 | 一种抗肝癌细胞转移的抑制剂组合物 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4689322A (en) * | 1982-07-28 | 1987-08-25 | Algina Aktiengesellschaft | Pharmaceutical products, calcium mixed salts of polymeric, anionic carboxylic acids and/or their esters of sulfuric acid, and methods for their preparation and use |
| CN1132209A (zh) * | 1995-03-27 | 1996-10-02 | 青岛海洋大学 | 一种新药多聚甘露糖醛酸硫酸盐 |
| CN1473836A (zh) * | 2003-08-04 | 2004-02-11 | 中国海洋大学 | 还原端1位为羧基的古罗糖醛酸寡糖及其衍生物 |
| CN1544475A (zh) * | 2003-11-25 | 2004-11-10 | 中国海洋大学 | 一种古糖酯及其制备方法和应用 |
| CN101691410A (zh) * | 2009-09-18 | 2010-04-07 | 中国海洋大学 | 一种具有防治胰岛素抵抗作用的海洋寡糖铬配合物 |
| CN102743409A (zh) * | 2012-06-18 | 2012-10-24 | 中国海洋大学 | 聚甘露糖醛酸丙酯硫酸盐在制备抗甲型h1n1流感病毒药物中的应用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0625304A (ja) | 1992-07-06 | 1994-02-01 | Higeta Shoyu Co Ltd | ガラクトサミン重合体硫酸化物及び該物質を 含有する抗ウイルス剤 |
| GB2317182B (en) | 1996-09-11 | 2000-11-01 | Johnson & Johnson Medical | Sulfated polysaccharides and uses thereof in medical treatment |
| JP4897310B2 (ja) | 2006-02-28 | 2012-03-14 | 理研食品株式会社 | L−グルロン酸金属塩又はd−マンヌロン酸金属塩の製造方法 |
| JP2008027767A (ja) | 2006-07-21 | 2008-02-07 | Aomori Prefecture | 固体高分子電解質膜及び燃料電池 |
| RU2553348C2 (ru) | 2010-03-10 | 2015-06-10 | Айновобайолоджик, Инк. | Продукт, содержащий глюкоманнан, ксантановую камедь и альгинат для лечения метаболических нарушений |
| CN104277130A (zh) * | 2013-07-02 | 2015-01-14 | 中国科学院上海药物研究所 | 一种硫酸酯化聚古洛糖酸多糖或其可药用盐及其制备方法和用途 |
-
2013
- 2013-07-02 CN CN201310275323.7A patent/CN104277130A/zh active Pending
-
2014
- 2014-07-02 CN CN201480038171.1A patent/CN105358582B/zh not_active Expired - Fee Related
- 2014-07-02 KR KR1020167002769A patent/KR102258569B1/ko not_active Expired - Fee Related
- 2014-07-02 DK DK14819337.8T patent/DK3018147T3/en active
- 2014-07-02 US US14/901,297 patent/US10058566B2/en not_active Expired - Fee Related
- 2014-07-02 WO PCT/CN2014/081472 patent/WO2015000411A1/zh not_active Ceased
- 2014-07-02 BR BR112015032849-0A patent/BR112015032849B1/pt not_active IP Right Cessation
- 2014-07-02 HU HUE14819337A patent/HUE038981T2/hu unknown
- 2014-07-02 MX MX2016000043A patent/MX373099B/es active IP Right Grant
- 2014-07-02 ES ES14819337.8T patent/ES2674976T3/es active Active
- 2014-07-02 SG SG11201510717SA patent/SG11201510717SA/en unknown
- 2014-07-02 AU AU2014286711A patent/AU2014286711B2/en not_active Ceased
- 2014-07-02 JP JP2016522246A patent/JP6757249B2/ja not_active Expired - Fee Related
- 2014-07-02 EP EP14819337.8A patent/EP3018147B1/en not_active Not-in-force
- 2014-07-02 PL PL14819337T patent/PL3018147T3/pl unknown
- 2014-07-02 CA CA2916749A patent/CA2916749C/en not_active Expired - Fee Related
- 2014-07-02 EA EA201690123A patent/EA028655B1/ru unknown
- 2014-07-02 TR TR2018/09674T patent/TR201809674T4/tr unknown
- 2014-07-02 PT PT148193378T patent/PT3018147T/pt unknown
-
2015
- 2015-12-23 ZA ZA2015/09353A patent/ZA201509353B/en unknown
-
2019
- 2019-02-22 JP JP2019030255A patent/JP6772318B2/ja not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4689322A (en) * | 1982-07-28 | 1987-08-25 | Algina Aktiengesellschaft | Pharmaceutical products, calcium mixed salts of polymeric, anionic carboxylic acids and/or their esters of sulfuric acid, and methods for their preparation and use |
| CN1132209A (zh) * | 1995-03-27 | 1996-10-02 | 青岛海洋大学 | 一种新药多聚甘露糖醛酸硫酸盐 |
| CN1473836A (zh) * | 2003-08-04 | 2004-02-11 | 中国海洋大学 | 还原端1位为羧基的古罗糖醛酸寡糖及其衍生物 |
| CN1544475A (zh) * | 2003-11-25 | 2004-11-10 | 中国海洋大学 | 一种古糖酯及其制备方法和应用 |
| CN101691410A (zh) * | 2009-09-18 | 2010-04-07 | 中国海洋大学 | 一种具有防治胰岛素抵抗作用的海洋寡糖铬配合物 |
| CN102743409A (zh) * | 2012-06-18 | 2012-10-24 | 中国海洋大学 | 聚甘露糖醛酸丙酯硫酸盐在制备抗甲型h1n1流感病毒药物中的应用 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Davydova et al. | Cytokine-inducing and anti-inflammatory activity of chitosan and its low-molecular derivative | |
| KR101594552B1 (ko) | 알킬화된 반합성 글리코사미노글리코산 에테르 및 이의 제조 및 사용 방법 | |
| AU2015228870B2 (en) | Carbohydrate ligands that bind to IgM antibodies against myelin-associated glycoprotein | |
| CN113135906A (zh) | 一种能够特异性检测脂滴内极性变化的脂滴靶向荧光探针 | |
| Huang et al. | Evaluation of sulfated α-glucans from Poria cocos mycelia as potential antitumor agent | |
| Tang et al. | Structure of a polysaccharide MDP2-1 from Melastoma dodecandrum Lour. and its anti-inflammatory effects | |
| CN103382229B (zh) | 一种具有免疫调节作用的新型海胆黄多糖的制备方法及结构鉴定 | |
| JP6772318B2 (ja) | 硫酸化ポリグルロン酸多糖又はその薬学的塩、その調製方法及びその使用 | |
| CN109071585A (zh) | 预防和治疗半乳糖凝集素相关疾病的硒代半乳糖苷化合物及其用途 | |
| JP2748001B2 (ja) | プソイドプテロシンの合成誘導体、及びそれを含む剤 | |
| CN111249235B (zh) | 一种载有正电聚合物/miR-195复合物的脑靶向纳米脂质体及其制备方法与应用 | |
| US20220265697A1 (en) | ß-GLUCAN COMPOSITION AND USE THEREFOR | |
| CN102746346A (zh) | 以碳原子为连接点的富勒烯单糖衍生物及其制备方法 | |
| US11524026B2 (en) | Heparanase inhibitors for treatment of diabetes | |
| CN114901702B (zh) | 一种糖胺聚糖衍生物及其应用 | |
| Wang et al. | Elucidating the structures and antitumor activities of Pleione bulbocodioides polysaccharides | |
| Stern | A new approach to tumour immunity | |
| CN109134694B (zh) | 一种金钗石斛多糖的硫酸化衍生物及其制备方法和用途 | |
| HK1220984B (zh) | 一种硫酸酯化聚古洛糖酸多糖或其可药用盐及其制备方法和用途 | |
| Xie et al. | A dual-target pectin-like polysaccharide LRP01B from Lamiophlomis rotata induces pancreatic cancer cell apoptosis in vitro and in vivo by causing mitochondrial dysfunction | |
| CN116535532A (zh) | 一种小球藻甘露半乳聚糖或其硫酸酯化合物和应用 | |
| KR101836641B1 (ko) | C-메틸로테노이드계 화합물을 함유하는 혈관염증질환의 예방 또는 치료용 약학적 조성물 | |
| CN120939019A (zh) | 嘧啶并三嗪二酮衍生物在制备抑制人类蛋白酶caspase-1活性的药物中的应用 | |
| WO2024181026A1 (ja) | 組成物 |