CN118085120A - Qihong polysaccharide KBPW1 with anti-tumor activity and application thereof in preparation of anti-tumor drugs - Google Patents
Qihong polysaccharide KBPW1 with anti-tumor activity and application thereof in preparation of anti-tumor drugs Download PDFInfo
- Publication number
- CN118085120A CN118085120A CN202410402982.0A CN202410402982A CN118085120A CN 118085120 A CN118085120 A CN 118085120A CN 202410402982 A CN202410402982 A CN 202410402982A CN 118085120 A CN118085120 A CN 118085120A
- Authority
- CN
- China
- Prior art keywords
- polysaccharide
- tumor
- kbpw
- kbpw1
- glcp
- 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.)
- Pending
Links
- 229920001282 polysaccharide Polymers 0.000 title claims abstract description 140
- 239000005017 polysaccharide Substances 0.000 title claims abstract description 140
- 150000004676 glycans Chemical class 0.000 title claims abstract description 139
- 230000000259 anti-tumor effect Effects 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims description 6
- 239000002246 antineoplastic agent Substances 0.000 title abstract description 8
- 229940041181 antineoplastic drug Drugs 0.000 title abstract description 8
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 46
- 206010009944 Colon cancer Diseases 0.000 claims abstract description 21
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims abstract description 20
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 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 claims abstract description 9
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 claims abstract description 9
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229930182830 galactose Natural products 0.000 claims abstract description 8
- 239000008103 glucose Substances 0.000 claims abstract description 8
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 claims abstract description 7
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 claims abstract description 5
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims abstract description 5
- 239000007788 liquid Substances 0.000 claims description 21
- 238000010521 absorption reaction Methods 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 239000000843 powder Substances 0.000 claims description 5
- 206010029260 Neuroblastoma Diseases 0.000 claims description 4
- -1 adsorption carrier Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 208000005017 glioblastoma Diseases 0.000 claims description 4
- 238000001179 sorption measurement Methods 0.000 claims description 3
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 208000018142 Leiomyosarcoma Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 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
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 2
- 239000007884 disintegrant Substances 0.000 claims description 2
- 239000003623 enhancer Substances 0.000 claims description 2
- 239000000945 filler Substances 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 239000007937 lozenge Substances 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 239000006186 oral dosage form Substances 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 239000000080 wetting agent Substances 0.000 claims description 2
- 241000699670 Mus sp. Species 0.000 abstract description 30
- 230000000694 effects Effects 0.000 abstract description 24
- 230000012010 growth Effects 0.000 abstract description 6
- 230000005012 migration Effects 0.000 abstract description 6
- 238000013508 migration Methods 0.000 abstract description 6
- 230000035755 proliferation Effects 0.000 abstract description 6
- 231100000331 toxic Toxicity 0.000 abstract description 6
- 230000002588 toxic effect Effects 0.000 abstract description 6
- 201000011510 cancer Diseases 0.000 abstract description 5
- 239000013543 active substance Substances 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 239000004480 active ingredient Substances 0.000 abstract description 2
- 230000001093 anti-cancer Effects 0.000 abstract description 2
- 230000007547 defect Effects 0.000 abstract description 2
- 230000009545 invasion Effects 0.000 abstract description 2
- 230000000214 effect on organisms Effects 0.000 abstract 1
- 238000000605 extraction Methods 0.000 description 23
- 210000004027 cell Anatomy 0.000 description 22
- 244000269722 Thea sinensis Species 0.000 description 20
- 235000013616 tea Nutrition 0.000 description 18
- 101000883798 Homo sapiens Probable ATP-dependent RNA helicase DDX53 Proteins 0.000 description 15
- 102100038236 Probable ATP-dependent RNA helicase DDX53 Human genes 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 239000000243 solution Substances 0.000 description 14
- 230000005764 inhibitory process Effects 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 150000002772 monosaccharides Chemical class 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 230000004044 response Effects 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 238000004192 high performance gel permeation chromatography Methods 0.000 description 5
- 238000007069 methylation reaction Methods 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 238000013461 design Methods 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 229960002949 fluorouracil Drugs 0.000 description 4
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000011987 methylation Effects 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 210000001541 thymus gland Anatomy 0.000 description 4
- 238000005303 weighing Methods 0.000 description 4
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 3
- 244000146486 Glehnia littoralis Species 0.000 description 3
- 235000004036 Glehnia littoralis Nutrition 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001720 carbohydrates Chemical class 0.000 description 3
- 235000014633 carbohydrates Nutrition 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000003205 fragrance Substances 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 238000003304 gavage Methods 0.000 description 3
- 239000000413 hydrolysate Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000004255 ion exchange chromatography Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- OQUKIQWCVTZJAF-UHFFFAOYSA-N phenol;sulfuric acid Chemical compound OS(O)(=O)=O.OC1=CC=CC=C1 OQUKIQWCVTZJAF-UHFFFAOYSA-N 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 230000004614 tumor growth Effects 0.000 description 3
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 2
- 229920002271 DEAE-Sepharose Polymers 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 2
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 229920005654 Sephadex Polymers 0.000 description 2
- 239000012507 Sephadex™ Substances 0.000 description 2
- 235000006468 Thea sinensis Nutrition 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 235000020279 black tea Nutrition 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000012292 cell migration Effects 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000004737 colorimetric analysis Methods 0.000 description 2
- 238000005100 correlation spectroscopy Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 125000003147 glycosyl group Chemical group 0.000 description 2
- 238000000990 heteronuclear single quantum coherence spectrum Methods 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000001035 methylating effect Effects 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000005211 surface analysis Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 229910021642 ultra pure water Inorganic materials 0.000 description 2
- 239000012498 ultrapure water Substances 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- CBOJBBMQJBVCMW-BTVCFUMJSA-N (2r,3r,4s,5r)-2-amino-3,4,5,6-tetrahydroxyhexanal;hydrochloride Chemical compound Cl.O=C[C@H](N)[C@@H](O)[C@H](O)[C@H](O)CO CBOJBBMQJBVCMW-BTVCFUMJSA-N 0.000 description 1
- HNSDLXPSAYFUHK-UHFFFAOYSA-N 1,4-bis(2-ethylhexyl) sulfosuccinate Chemical compound CCCCC(CC)COC(=O)CC(S(O)(=O)=O)C(=O)OCC(CC)CCCC HNSDLXPSAYFUHK-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 101500000959 Bacillus anthracis Protective antigen PA-20 Proteins 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 102400000888 Cholecystokinin-8 Human genes 0.000 description 1
- 101800005151 Cholecystokinin-8 Proteins 0.000 description 1
- AEMOLEFTQBMNLQ-BZINKQHNSA-N D-Guluronic Acid Chemical compound OC1O[C@H](C(O)=O)[C@H](O)[C@@H](O)[C@H]1O AEMOLEFTQBMNLQ-BZINKQHNSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-VANFPWTGSA-N D-mannopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H]1O AEMOLEFTQBMNLQ-VANFPWTGSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- 108010087230 Sincalide Proteins 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 238000004115 adherent culture Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- AEMOLEFTQBMNLQ-UHFFFAOYSA-N beta-D-galactopyranuronic acid Natural products OC1OC(C(O)=O)C(O)C(O)C1O AEMOLEFTQBMNLQ-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000003560 cancer drug Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 238000010609 cell counting kit-8 assay Methods 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 235000021045 dietary change Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000012154 double-distilled water Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960001911 glucosamine hydrochloride Drugs 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000008821 health effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000001052 heteronuclear multiple bond coherence spectrum Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000005917 in vivo anti-tumor Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 238000013178 mathematical model Methods 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 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
- 238000003305 oral gavage Methods 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 235000011225 shan shi Nutrition 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a Qihong polysaccharide KBPW1 with anti-tumor activity and application thereof in preparing anti-tumor drugs, and relates to the technical field of plant polysaccharide active substances and application thereof. The repeatable primary structural unit of the keemun polysaccharide KBPW contains →4)-β-D-Glcp-(1→、α-L-Araf-(1→、→3)-β-D-Galp-(1→、→5)-α-L-Araf-(1→、→3,5)-β-L-Araf-(1→、β-D-Glcp-(1→、→4,6)-β-D-Glcp-(1→、→6)-β-D-Glcp-(1→ eight glycosidic bonds, which consists of arabinose, galactose and glucose, wherein the molar ratio of the arabinose to the galactose to the glucose is 2.62:1.02:6.36; the relative molecular mass is 3.8X10 3 Da. The beneficial effects are that: as an anticancer active ingredient, the composition can obviously inhibit the growth, proliferation and migration invasion of colorectal cancer CT26WT cells, reduce the tumor volume and weight of CT26WT tumor-bearing mice, has the characteristics of small toxic and side effects on organisms, good biocompatibility, strong specificity, low toxic and side effects and the like, can make up the defects of the traditional cancer treatment means, and can be used for developing new anticancer drugs.
Description
Technical Field
The invention relates to the technical field of plant polysaccharide active substances and application thereof, in particular to a keemun polysaccharide KBPW1 with anti-tumor activity and application thereof in preparing anti-tumor drugs.
Background
Tumors have been one of the major public health problems worldwide, severely compromising human health. In recent years, the morbidity and mortality of tumors are gradually increased, and according to the global cancer statistics report in 2020, 457 cases of new cancer cases and 300 cases of death cases are newly increased in China every year, accounting for 23.7% of the world, and the new cases and the death population of the world are far beyond those of other countries. The traditional treatment method of the tumor at present mainly adopts the combination of surgery, chemotherapy and radiotherapy, but the curative effect is not ideal, the toxic and side effects of the traditional anti-tumor medicine are large, normal cells and immune cells of a body are destroyed while tumor cells in a patient are killed, various tissues and organs are damaged, the prognosis is poor, and the malignant progress is rapid. Therefore, there is a need to develop new and highly targeted cancer treatment methods and drugs to improve the quality of life and survival time of cancer patients, and to find safe, efficient and specific natural antitumor new drugs gradually becomes the goal of the middle and outer scientific research workers.
The Qimen black tea (hereinafter called Qimen for short) is one of three-major high-aroma black tea in the world and ten-major famous tea in China, and is mainly produced in the Qimen county of Huang Shanshi Anhui province in China, and is popular among consumers all the time because the special fragrance like flowers, fruits and honey, namely the fragrance like Qimen, is known as the fragrance of group. The literature records that the medical history of the keemun has more than one hundred years, and the long-term drinking of the tea has various health effects of nourishing stomach, protecting stomach, promoting the production of body fluid, clearing heat, promoting urination, diminishing inflammation, sterilizing, refreshing, relieving fatigue, resisting aging, preventing cardiovascular and cerebrovascular diseases and the like. Modern pharmacological researches show that tea polysaccharide is a key component of tea to exert various biological activities, and has remarkable curative effects on aspects of resisting tumor, improving immunity, resisting oxidation and the like. The chemical structure of tea polysaccharide is the material basis for exerting biological activity, while keemun has different structure and physiological activity from other tea leaves due to the special fermentation process and production place, and deserves intensive research.
At present, the main active components of the keemun polysaccharide are not clear, the active substance basis and the efficacy of the keemun polysaccharide are still to be clear, meanwhile, the fine chemical structure of the keemun polysaccharide is not reported, and the keemun polysaccharide with the anticancer activity, which has the clear chemical structure and uniform composition, is prepared by a suitable extraction and purification process, so that the research and development of novel anticancer drugs of the keemun polysaccharide are limited.
The Chinese patent application document with publication number of CN105859903A discloses a radix glehniae polysaccharide, a preparation method and application thereof, and relates to the technical field of polysaccharides. The molecular weight of the glehnia littoralis polysaccharide is 26.3kDa; the monosaccharide composition and the molar ratio of the glehnia littoralis polysaccharide are as follows: rhamnose: galactose: glucose = 2.05:1.00:7.06; and provides a primary structure repeating unit of the glehnia littoralis polysaccharide. The radix Glehniae polysaccharide has the advantages of simple extraction process, high component purity, good anti-tumor and antioxidant activity, and small toxic and side effects. However, the patent does not disclose the keemun polysaccharide KBPW1 and its use according to the present invention.
Disclosure of Invention
The technical problem to be solved by the invention is how to provide the keemun polysaccharide with anti-tumor activity.
The invention solves the technical problems by the following technical means:
in a first aspect of the present invention, a keemun polysaccharide KBPW with anti-tumor activity is provided, wherein a repeatable primary structural unit of the keemun polysaccharide KBPW1 contains →4)-β-D-Glcp-(1→、α-L-Araf-(1→、→3)-β-D-Galp-(1→、→5)-α-L-Araf-(1→、→3,5)-β-L-Araf-(1→、β-D-Glcp-(1→、→4,6)-β-D-Glcp-(1→、→6)-β-D-Glcp-(1→ eight glycosidic bonds; the connection mode of the glycosidic bond is shown as formula 1:
The beneficial effects are that: the keemun polysaccharide KBPW-1 provided by the invention has novel structure, definite chemical structure and uniform composition, and the in-vitro and in-vivo experiments of cells prove that the keemun polysaccharide KBTP-1 has good anti-tumor effect.
Preferably, the relative molecular mass of the keemun polysaccharide KBPW is 3.8X10 3 Da.
Preferably, the keemun polysaccharide KBPW is composed of arabinose, galactose and glucose, and the molar ratio of the arabinose, galactose and glucose is 2.62:1.02:6.36.
The second aspect of the invention provides an application of the Qihong polysaccharide KBPW1 in preparing an anti-tumor medicament.
Preferably, the tumor comprises colorectal cancer (CRC), cholangiocarcinoma, gastric cancer, glioblastoma (GBM), leiomyosarcoma, melanoma, lung cancer, neuroblastoma (NB), ovarian cancer, pancreatic cancer, prostate cancer, thyroid cancer, breast cancer, or any combination thereof.
The third aspect of the present invention provides an antitumor pharmaceutical composition, which comprises the above-mentioned keemun polysaccharide KBPW.
Preferably, the composition further comprises one or more pharmaceutically acceptable carriers.
Preferably, the pharmaceutically acceptable carrier is a diluent, excipient, filler, binder, wetting agent, disintegrant, absorption enhancer, adsorption carrier, surfactant or lubricant.
Preferably, the pharmaceutically acceptable carrier is a diluent.
Preferably, the oral dosage form of the pharmaceutical composition comprises a tablet, a capsule, a lozenge, an oral liquid, a granule, a pill or a powder.
Compared with the prior art, the invention has the beneficial technical effects that:
1. The Qihong polysaccharide KBPW1 provided by the invention has novel structure, definite chemical structure and uniform composition, and the in-vitro and in-vivo experiments of cells prove that the Qihong polysaccharide KBPW1 has good anti-tumor effect, can relieve weight loss caused by 5-Fu, improve the immune organ index and liver function of mice, and overcomes the defect of large side effect of the existing chemical anticancer drugs on organisms.
2. The Qihong polysaccharide KBPW1 provided by the invention can obviously inhibit the growth, proliferation and migration invasion of colorectal cancer CT26 WT cells, the tumor growth of tumor-bearing mice given with the polysaccharide in animal experiments can be effectively inhibited, the tumor inhibition rate can reach 71.26%, and the vital signs of the tumor-bearing mice are still obviously better than those of control groups without the polysaccharide and the positive drug 5-FU when the administration concentration reaches high concentration of 200 mg/kg.
3. The keemun polysaccharide has good anti-tumor activity in vitro and in vivo, can obviously inhibit the growth and proliferation of colorectal cancer, has no toxic or side effect, and has not been reported at present.
4. The invention provides a brand-new keemun polysaccharide compound, which has a definite chemical structure, and through high performance liquid chromatography (HPGPC) analysis, the keemun polysaccharide prepared by the method has only one absorption peak, has the molecular weight of 3.8X10 3 Da, has stronger anti-tumor activity, and can be used as a novel active ingredient for preparing anti-colorectal cancer drugs.
5. The method for preparing the active polysaccharide has high efficiency and stable activity.
Drawings
FIG. 1 is a graph showing the effect of the feed to liquid ratio (A), temperature (B) and time (C) on the yield of Keemun polysaccharide in example 1 of the present invention;
FIG. 2 is a response surface analysis chart of the factor design of the preparation process of the Keemun polysaccharide in example 1 of the invention; a-B: feed liquid ratio and temperature; C-D: feed liquid ratio and time; E-F: time and temperature;
FIG. 3 is a graph showing the elution of the Qihong polysaccharide KBPW1 in example 2 of the present invention; a is DEAE-Sepharose Fast Flow ion exchange chromatographic column elution curve of Qihong polysaccharide KBPW; b is the elution curve of a Sephadex G-100 gel column of the Qihong polysaccharide KBPW;
FIG. 4 is an Ultraviolet (UV) full-wavelength scan (A) and HPGPC molecular weight chromatogram (B) of Qihong polysaccharide KBPW1 of example 3 of the present invention;
FIG. 5 is a Fourier infrared spectrum (FT-IR) of the Qihong polysaccharide KBPW of example 3 of the invention;
FIG. 6 is a Scanning Electron Microscope (SEM) image of the Qihong polysaccharide KBPW1 of example 3 of the present invention;
FIG. 7 is a diagram showing the monosaccharide composition Ion Chromatography (IC) of the Qihong polysaccharide KBPW1 of example 3 of the present invention;
FIG. 8 is a chart of a glycosidic bond type mass spectrum (GC-MS) of the Qihong polysaccharide KBPW1 of example 4 of the present invention;
FIG. 9 is a nuclear magnetic resonance spectrum of the Qihong polysaccharide KBPW1 of example 4 of the present invention; a is 13 C. Carbon spectrum; b is 1 H hydrogen spectrum; c is HSQC spectrum; d is 1H-1 H COSY spectrum; e is HMBC spectrum;
FIG. 10 is a graph showing the inhibition of CT26 WT colorectal cancer cells by Qihong polysaccharide KBPW1 of example 5 of the present invention; wherein A is the inhibition of the proliferation of CT26-WT cells by Qihong polysaccharide KBTP-1; b is a migration condition diagram of cell scratches after carrying out treatment on the Qihong polysaccharide for 0, 24 and 48 hours by KBTP-1 with different concentrations;
FIG. 11 is a graph showing the tumor-inhibiting effect of the Qihong polysaccharide KBPW1 of example 6 on CT26 WT colorectal cancer tumor-bearing mice.
Detailed Description
For the purpose of making the objects, technical solutions and advantages of the embodiments of the present invention more apparent, the technical solutions in the embodiments of the present invention will be clearly and completely described in the following in conjunction with the embodiments of the present invention, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
The test materials, reagents and the like used in the examples described below are commercially available unless otherwise specified.
Those of skill in the art, without any particular mention of the techniques or conditions, may follow the techniques or conditions described in the literature in this field or follow the product specifications.
Example 1: response surface optimized keemun polysaccharide extraction process
(1) Removing impurities, taking proper amount of tea leaves, crushing by a crusher, sieving by a 80-mesh sieve, and drying and preserving in dark place for standby; accurately weighing tea powder, adding 95% ethanol according to a feed-liquid ratio of 1:20g/mL, stirring at 25deg.C and a rotation speed of 120rpm/min for 24h, suction filtering, collecting precipitate, and drying in a 55 deg.C oven to obtain decolorized and defatted dry tea powder;
(2) And (3) a single factor test, namely respectively setting the factors such as the feed liquid ratio (1:10, 1:20, 1:30, 1:40, 1:50 g/mL), the time (1, 1.5, 2, 2.5, 3 h), the temperature (60, 70, 80, 90, 100 ℃) and the like of the extracted keemun polysaccharide, taking the yield of the keemun polysaccharide as an index, examining the influence of various factor variables on the extraction rate of the keemun polysaccharide, and determining the optimal extraction process parameters.
(3) And adopting Box-Benhnken L 17(33) Design test scheme in Design-Expert 13 software to extract the feed liquid ratio, temperature and time of the Keemun polysaccharide as dependent variables and the polysaccharide yield as variables for response surface analysis. Each independent variable level was coded with-1, 0, 1, respectively, and experimental factors and level designs are shown in Table 1.
Table 1 coding level of response surface test independent variables
(4) Single factor experimental results:
As shown in fig. 1A, as the feed-to-liquid ratio increases, the extraction rate of the keemun polysaccharide tends to increase, and the extraction rate reaches the highest value at a feed-to-liquid ratio of 1:30g/mL, but as the feed-to-liquid ratio continues to increase, the polysaccharide yield starts to decrease. It is presumed that when the feed liquid is relatively low, the polysaccharide is not completely swelled, the extract is difficult to separate, the polysaccharide is affected to be precipitated, when the feed liquid is relatively high, the solution becomes thin, the intermolecular adsorption is enhanced, thereby causing the reduction of the polysaccharide extraction rate and the increase of the subsequent treatment cost of the solvent. Therefore, the optimal feed-to-liquid ratio is 1:30g/mL.
FIG. 1B shows that as the extraction temperature increases, the yield of the Keemun polysaccharide tends to increase and then decrease, and the polysaccharide yield reaches a maximum when the temperature is 90 ℃. The diffusion coefficient of polysaccharide increases with increasing extraction temperature, so that the content of polysaccharide in the aqueous solution increases. However, excessive temperatures can cause degradation of the polysaccharide, resulting in reduced polysaccharide yields, while increasing energy consumption. Therefore, the optimum extraction temperature is 90 ℃.
FIG. 1C shows that polysaccharide extraction rate showed a slow increasing trend with increasing extraction time, with a maximum polysaccharide yield of 5.35.+ -. 0.35% when time was 2.5h, but polysaccharide yield began to decrease after time exceeded 2.5h. This is because the extraction time is prolonged to make the dissolution of polysaccharide into the solvent simpler and faster, but too long an extraction time also results in degradation of polysaccharide, which reduces its yield. Therefore, the optimal extraction time is 2.5h.
(5) Response surface test results, on the basis of single factor test, the response surface test of L 17(33) is carried out by taking the liquid-material ratio, the extraction temperature and the extraction time as test factors, the extraction process of the Qihong polysaccharide is optimized, and the test design and the result are shown in Table 2. Performing multiple regression fitting on the data of table 2 by using Design-Expert 13.0 software to obtain a quadratic multiple regression equation of the yield (Y) of the keemun polysaccharide to the feed-liquid ratio (A), the temperature (B) and the time (C):
Y＝7.48+0.06400A+0.3563B+0.2013C-0.1750AB-0.0450AC+0.1475BC-0.6878A2-0.91
53B2-1.01C2。
TABLE 2 response surface test factor level and results
TABLE 3 analysis of variance
Note that: * p <0.05, representing a significant difference; * P <0.01, representing a very significant difference
Analysis of variance was performed on the regression mathematical model to verify the validity of the equation and the partial regression coefficient of each factor, as shown in table 3, the model selected for the test was extremely significant (P < 0.01), the mismatching term of variance was not significant (p=0.5787 > 0.05), and it was demonstrated that the influence of the non-test factors on the test results was not great. In addition, the value of the decision coefficient R 2 of the selected model is 0.9760, which indicates that the model is better fitted with an actual test, the value of the corrected decision coefficient R 2 Adj is 0.9451 and is close to the value of R 2, and the model has sufficient accuracy and universality. The influence of each factor on polysaccharide yield can be seen from the F value as: feed to liquid ratio > temperature > time. It can also be seen from the table that A, B, A 2、B2、C2 has a very significant effect on polysaccharide yield (P < 0.01), and that C has a significant effect on polysaccharide yield (P < 0.05); the effect of other factors is insignificant.
The response curve and contour diagram of interaction among the factors of the regression model are shown in fig. 2, and the optimal extraction process of the keemun crude polysaccharide obtained by the regression model comprises the following steps: the feed liquid ratio is 1:34.418g/mL, the temperature is 91.6057 ℃ and the time is 2.55097 hours, under the condition, the extraction rate of polysaccharide reaches 7.65811 percent, the feasibility is considered from the practical operation point of view, and the optimal extraction parameters are set as follows according to the model result and the practical situation: the feed liquid ratio is 1:30g/mL, the temperature is 90 ℃ and the time is 2.5 hours, the average yield of the obtained crude polysaccharide is 7.48+/-0.22%, and the average yield is basically consistent with the predicted result. The results show that optimal polysaccharide extraction process parameters can be obtained by using the method.
Example 2: preparation and purification of keemun polysaccharide
(1) Uniformly mixing the decolorized and defatted tea powder obtained in the example 1 with distilled water according to a feed liquid ratio of 1:30g/mL, stirring and extracting at 80 ℃ and a rotation speed of 120rpm/min for 2.5 hours, filtering, collecting filtrate, repeating for 2 times, and combining 3 times of filtrate to obtain a tea water extract;
(2) Concentrating the tea water extract in a rotary evaporator (35 rpm/min,55 ℃ and 0.09-0.10 MPa) under reduced pressure to 1/4 of the original volume, centrifuging at 4 ℃ and 10000rpm/min for 10min, discarding the precipitate, and collecting the supernatant concentrate; adding 4 times volume of absolute ethanol (to make final concentration of ethanol 80%) into the concentrated solution, precipitating (at room temperature) for 12 hr, filtering with gauze, collecting precipitate, and drying in oven at 55deg.C to obtain tea alcohol precipitate;
(3) Taking a tea alcohol sediment, adding a proper amount of deionized water (100 mL) until the tea alcohol sediment is completely dissolved, adding 1/4 volume (25 mL) of Sevag reagent (chloroform/n-butanol=4/1), magnetically stirring for 30min at room temperature, repeating for 4 times until no white protein layer exists, and collecting a supernatant polysaccharide solution; placing the polysaccharide solution with protein removed in a plate, sealing with a preservative film, freezing in a refrigerator at-20deg.C for 12 hr, and freeze-drying in a vacuum freeze dryer (-50deg.C, 10 Pa) for 48 hr to obtain tea polysaccharide sample;
(4) Using tea polysaccharide sample, preparing 20mg/mL tea polysaccharide solution, eluting with DEAE-Sepharose Fast Flow ion exchange column, sequentially gradient eluting with deionized water and 0.1, 0.2, 0.3, 0.4 and 0.5mol/L NaCl solution at 5mL/min, detecting polysaccharide content in the eluent by phenol-sulfuric acid colorimetric method, collecting sugar-containing eluent to obtain Qihong polysaccharide extract, and drawing elution curve as shown in figure 3A.
(5) Collecting the eluent of the main component deionized water, further purifying by using a Sephadex G-100 gel column, eluting with deionized water at a flow rate of 0.5mL/min, detecting the polysaccharide content in the eluent by a phenol-sulfuric acid colorimetric method, and drawing an elution curve as shown in figure 3B. Collecting polysaccharide-containing eluate, concentrating under reduced pressure, dialyzing, desalting, and vacuum lyophilizing to obtain Qihong polysaccharide component KBPW.
Example 3: physicochemical properties and structural characterization of Qihong polysaccharide KBPW1
(1) Carbohydrate content determination of Qihong polysaccharide KBPW1
The carbohydrate content of KBPW1 obtained in example 1 was determined by the phenol-sulfuric acid method, and the carbohydrate content in KBPW1 was 83.60.+ -. 0.79% by spectrophotometry at 490 nm.
(2) Ultraviolet spectral analysis of Qihong polysaccharide KBPW1
The Qihong polysaccharide KBPW1 is prepared into 0.1mg/mL solution, and is scanned in the wavelength range of 190-400 nm by using a full-wavelength scanning microplate reader, as shown in figure 4A, KBPB 1 has no absorption peak at 260nm and 280nm, which shows that KBPW1 almost contains no pigment, protein and nucleic acid.
(3) Homogeneity and weight average molecular weight determination of keemun polysaccharide KBPW1
The retention time of dextran standards of different molecular weights (5 KD, 25KD, 80KD, 150KD, 420KD, 670 KD) was determined by high performance gel permeation chromatography HPGPC, a molecular weight standard curve was drawn, and then the relative molecular weight was calculated from the standard curve and the peak time of the Qihong polysaccharide KBPW1 sample.
HPGPC detection conditions: chromatographic column: BRT105-103-101 series gel column (8X 300 mm); mobile phase: 0.05M NaCl solution; flow rate: 0.8mL/min; column temperature: 40 ℃; sample injection amount: 25 μl; a detector: differential detector RID-20A.
As a result, as shown in FIG. 4B, the Qihong polysaccharide KBPW is a homogeneous polysaccharide having a weight average molecular weight of: 3.8X10 3 Da.
(4) Apparent morphology analysis of Qihong polysaccharide KBPW1
Analyzing the apparent morphology of the Qihong polysaccharide KBPW by adopting a scanning electron microscope, weighing 2mg of KBPB 1, adhering the obtained product to a metal iron block by using conductive adhesive, spraying a layer of gold on the surface of a polysaccharide sample by using a spraying instrument, and then observing the apparent morphology by using the scanning electron microscope. As a result, as shown in FIG. 6, KBPW a surface was uniformly smooth and exhibited an irregular lamellar structure.
(5) Characteristic group analysis of Qihong polysaccharide KBPW1
Analyzing characteristic groups of the Qihong polysaccharide KBPW mg, the Qihong polysaccharide KBPW and the potassium bromide 100mg by adopting a Fourier infrared spectrometer, uniformly mixing, grinding, drying, fixing and tabletting, and then placing on a Nicolet 67 type Fourier infrared spectrometer for scanning analysis, wherein the scanning range is 4000cm -1-500cm-1. As a result, as shown in FIG. 5, the Qihong polysaccharide KBPW has typical characteristic peaks of polysaccharide, a strong absorption peak is a stretching vibration of-OH at 3405.19cm -1, an absorption peak at 2923.07cm -1 is a stretching vibration of C-H in CH 2 group, an absorption peak at 1617.33cm -1 is a stretching vibration of C=O, and an absorption peak at 1401.24cm -1 is related to a C-H bending vibration; the strong absorption peak at 1100.29cm -1, which is due to the stretching vibration of the pyran ring of the glycosyl residue, is related to the β -and α -glycosidic bonds contained in the polysaccharide at 963.75cm -1 and 640.73cm -1.
(6) Monosaccharide composition analysis of Qihong polysaccharide KBPW1
The monosaccharide composition of the Qihong polysaccharide KBPW is measured by using a Thermo ICS5000 ion chromatograph, 5mg KBPB 1 is precisely weighed and placed in an ampoule bottle, 3mol/L trifluoroacetic acid (TFA) 2mL is added, hydrolysis is carried out for 3h at 120 ℃, the acid hydrolysis solution is accurately sucked and transferred into a tube, after nitrogen is blown dry, 5mL ultra-pure water is added, vortex mixing is carried out, and centrifugation is carried out for 5min at 12000 rpm. Taking supernatant and transferring the supernatant into a chromatographic bottle for testing. And accurately weighing the monosaccharide standard substances of 5mg each, including fucose, rhamnose, arabinose, galactose, glucose, xylose, mannose, fructose, ribose, galacturonic acid, glucuronic acid, amino galactose hydrochloride, glucosamine hydrochloride, N-acetyl-D glucosamine, guluronic acid and mannuronic acid, and preparing monosaccharide mixed standard solutions with different concentration gradients, determining the mass of different monosaccharides according to an absolute quantitative method and calculating the molar ratio according to the molar mass of the monosaccharides.
IC detection conditions: chromatographic column: dionex Carbopac TM PA20 (3 x 150 mm); mobile phase: h 2 O; b15 mM NaOH; 15mM NaOH&100mM NaOAc; flow rate: 0.3mL/min; sample injection amount: 25 μL; column temperature: 30 ℃; elution gradient: 0min A/B/C (98.8:1.2:0, V/V), 18min A/B/C (98.8:1.2:0, V/V), 20min A/B/C (50:50:0, V/V), 30min A/B/C (50:50:0, V/V), 30.1min A/B/C (0:0:100, V/V), 46min A/B/C (0:0:100, V/V), 46.1min A/B/C (0:100:0, V/V), 50min A/B/C (0:100:0, V/V), 50.1min A/B/C (98.8:1.2:0, V/V), 80min A/B/C (98.8:1.2:0, V/V). A detector: an electrochemical detector.
As a result, as shown in FIG. 7, KBPW1 was composed of arabinose Ara, galactose Gal, and glucose Glc in a molar ratio of 2.62:1.02:6.36.
Example 4: structure identification of Qihong polysaccharide KBPW1
(1) Analysis of the glycosidic bond composition of Qihong polysaccharide KBPW1
And adopting gas chromatography-mass spectrometry (GC-MS) to analyze the type of the glycosidic bond of KBPW1.20 mg KBPB 1, placing the mixture in a glass reaction bottle, adding 1mL anhydrous DMSO, adding a methylating reagent A liquid for sealing according to a methylation kit (BRT-JJH) instruction book, adding a methylating reagent B liquid after ultrasonic dissolution, adding 2mL ultrapure water after stirring in a water bath at 30 ℃ for 60min for reaction, terminating the methylation reaction, and finally concentrating, dialyzing and freeze-drying the reaction liquid to obtain a completely methylated polysaccharide sample.
Taking a methylated polysaccharide sample, placing the sample in an ampoule bottle, adding 1mL of TFA (2 mol/L), hydrolyzing for 90min at 110 ℃, and steaming until the TFA is completely removed, thus obtaining a complete hydrolysate. 2mL of double distilled water and 60mg of sodium borohydride (NaBH 4) are added to the hydrolysate for reduction reaction, glacial acetic acid is added to the hydrolysate for neutralization after 8 hours, after the redundant NaBH4 is removed by rotary evaporation, 1mL of acetic anhydride is added for reaction at 100 ℃ for 1 hour, 3mL of toluene is added after cooling, after the redundant acetic anhydride is evaporated to dryness by decompression concentration, dichloromethane (CH 2Cl2) is added for extracting an acetylation product, and the extract is dried by anhydrous sodium sulfate and then subjected to GC-MS measurement.
GC-MS detection conditions: agilent 7890A-5977B system, column: RXI-5SIL MS (30 m.times.0.25 mm.times.0.25 um); temperature programming conditions: heating to a starting temperature of 120 ℃ at 3 ℃/min to 250 ℃/min; maintaining for 5min; sample inlet temperature: 250 ℃, detector temperature: the carrier gas is helium at 250 ℃ with a flow rate of 1mL/min; ion flame detector, mass scan range (m/z): 50-350.
As a result, as shown in FIG. 8, the KBPW methylation products showed eight methylation derivative ion peaks in the gas chromatograph, and the type of glycosidic bond and the molar ratio of the Qihong polysaccharide KBPW1 were obtained by analyzing each mass spectrum by on-line searching according to the retention time of each peak as shown in Table 4.
(2) Glycoside linkage analysis of Qihong polysaccharide KBPW1
The glycosidic linkage mode of nuclear magnetic resonance analysis KBPW is adopted: 50mg KBPB 1 was dissolved in 1mL of heavy water, the solution was transferred into a nuclear magnetic resonance tube, and the sample was scanned using AGILENT VNMRS600 superconducting nuclear magnetic resonance spectrometer. One-dimensional 1H-NMR、13 C-NMR spectra and two-dimensional 1H-1 H COSY, HMBC, HSQC spectra were obtained (FIG. 9).
From FIG. 9, it is understood that the chemical shift assignment of 13C、1 H of each sugar residue KBPW is shown in Table 5, and substantially corresponds to the monosaccharide composition and methylation structure. Through the above structural characterization of KBPW, the chemical structural formula of KBPW1 according to the present invention can be obtained as follows:
Table 4KBPW type of glycosidic bond
| Sequence number | Retention time (min) | Glycosyl derivatives | Molar ratio of | Glycosidic bond connection mode |
| 1 | 10.412 | 2,3,5-Me3-Araf | 16.2 | Araf-(1→ |
| 2 | 15.098 | 2,3-Me2-Araf | 8.5 | →5)-Araf-(1→ |
| 3 | 16.862 | 2,3,4,6-Me4-Glcp | 4.8 | Glcp-(1→ |
| 4 | 18.412 | 2-Me1-Araf | 7.2 | →3,5)-Araf-(1→ |
| 5 | 20.768 | 2,3,6-Me3-Glcp | 45.5 | →4)-Glcp-(1→ |
| 6 | 21.322 | 2,4,6-Me3-Galp | 11.4 | →3)-Galp-(1→ |
| 7 | 22.06 | 2,3,4-Me3-Glcp | 2.6 | →6-Glcp-(1→ |
| 8 | 26.55 | 2,3-Me2-Glcp | 3.8 | →4,6)-Glcp-(1→ |
TABLE 5 chemical shifts of the glycosidic linkages 1 H and 13 C
Example 5: migration inhibition effect of Qihong polysaccharide KBPW1 on CT26 WT colorectal cancer cells in vitro
(1) Cell proliferation assay
The effect of Qihong polysaccharide KBPW1 prepared in example 1 on the activity of CT26 WT of colorectal cancer cells of mice was detected by CCK8, CT26.WT cells in the logarithmic phase of growth were taken, their cell concentration was adjusted to 5X 10 4/mL, inoculated into 96-well plates, 100. Mu.L of cell suspension per well was placed in an incubator at 37℃and 5% CO 2 for wall-attached culture for 24 hours, KBPW1 was added at final concentrations of 50, 100, 200, 400, 600, 800. Mu.g/mL, and a blank medium control group was set at the same time, and after incubation was continued for 24 hours, CCK-8 (10. Mu.L) was added to each well for incubation for 2 hours. Finally, the OD value of each hole is measured by an enzyme-labeled instrument at the wavelength of 450nm, and the effect of the Qihong polysaccharide KBPW on the tumor cell activity is calculated. Cell viability (%) = (OD dosing group-OD blank)/(OD control group-OD blank) ×100% the cell viability of the control group was set to 100%.
As shown in FIG. 10A, after incubation of CT26.WT cells with Qihong polysaccharide KBPW, the inhibitory activity of KBTP-1 on CT26-WT cells increased with increasing KBPW1 concentration, and the cell viability was less than 50% when KBPW concentration was 800. Mu.g/mL, demonstrating that Qihong polysaccharide KBPW1 inhibited proliferation of CT26 WT cells to some extent.
(2) Cell scratch assay: CT26-WT cells were inoculated into 6-well plates at a cell density of 1X 10 6 cells per well, and after 24 hours of adherent culture, vertically and uniformly streaked at the center of each well with a 200. Mu.L gun head, and then cultured in a serum-free medium containing KBPW1 at 100, 200, 400. Mu.g/mL. At time nodes of 0h,24h and 48h of culture, the scratch change condition is observed under a fluorescence inversion microscope, and the change of the CT26-WT cell migration capacity is recorded.
As shown in FIG. 10B, it can be seen that CT26-WT cells have a greatly reduced migration capacity after KBPW's 1 incubation. And the cell migration capacity is reduced along with the increase of KBPW1 concentration, which shows that KBPW can obviously inhibit the migration of colon cancer cells CT26-WT, and the inhibition effect is dose-dependent.
Example 6: research on antitumor activity of Qihong polysaccharide KBPW in vivo
Colorectal cancer CT26 WT cell xenograft is adopted to construct a tumor-bearing mouse model, different doses of Qihong polysaccharide KBPW1 are given to oral gastric lavage, and the anti-tumor activity of KBPW is analyzed.
(1) Colorectal cancer tumor-bearing mouse model construction and drug administration intervention
After 5-week-old male BALB/C mice were adaptively bred in SPF-class animal houses at 23.+ -. 2 ℃ under conditions of relative humidity of 50% -60%, 12h light and 12h darkness for one week, 72 mice were randomly picked up, and CT26 WT colorectal cancer was inoculated to the remaining mice except for the Normal group (Normal, 12 mice), CT26 WT cell suspensions (2X 10 6/mL) in the log phase of growth were extracted by a 1mL microinjector, inoculated to the right underarm of 60 BALB/C mice after sterilization, each inoculated with 0.2mL (2X 10 6/mL), and the injection points were pressed to prevent extracellular leakage, and tumor-bearing mice after CT26.WT colorectal cancer cell inoculation were randomly divided into 5 groups of 12 mice each: model, lavage sterile saline; positive group (Positive, lavage 5-fluorouracil, 20 mg/kg. DBW); KBPW1 low dose group (KBPW-L, 50 mg/kg.dBW), KBPW1 medium dose group (KBPW-M, 100 mg/kg.dBW), KBPW1 high dose group (KBPW-H, 200 mg/kg.dBW), wherein the solvents configuring the Positive and KBPW1 groups were sterile physiological saline. Each group was given by oral gavage 1 time a day, and the mice were sacrificed by CO 2 asphyxiation and tested for relevant indicators at a gavage volume of 0.1mL/10g for 15 days continuously.
(2) Detection index of in-vivo antitumor activity of mice
General observations: the mice were observed daily for their mental state, activity, hair gloss, etc.
Body weight and diet drinking water detection: during the experiment, from day 0 of starting the gavage to day 15 of ending the gavage, the weight, diet and drinking water changes of each group of mice were monitored and recorded every 3 days at regular intervals, and weight and diet change curves were plotted.
Determination of tumor volume: during the period of gastric lavage administration, the length and the diameter of the tumor of the mice are measured by a vernier caliper every 3 days, and the growth condition of the tumor of the mice is monitored and recorded regularly; the tumor volume was calculated according to the formula v=0.5ab 2 (long diameter of a-tumor, short diameter of b-tumor), the tumor volume change curve was drawn, and the relative volume of tumor and relative tumor proliferation rate were calculated.
Tumor inhibition rate assay: after the gastric lavage administration treatment is finished, the axillary tumor of each group of mice is dissected and taken out, and the tumor inhibition rate is calculated after weighing, measuring and photographing. Tumor inhibition% = (average tumor weight of 1-administration group/average tumor weight of model control group) ×100%
Measurement of organ index: after the experiment, the thymus of the mice was taken out, the physiological saline was rinsed, the filter paper was dried with the physiological saline, and then the samples were sequentially weighed, and the thymus index= (thymus weight/animal weight) ×100%.
(3) Experimental results
In vivo experiments of anti-CT 26 WT colorectal cancer tumor-bearing mice of the Qihong polysaccharide KBPW1 show that the volume and weight of the right armpit tumor mass of the mice in the model control group are increased and enlarged continuously along with the time, and the KBPW1 administration group can obviously inhibit the tumor growth of the tumor-bearing mice, and the tumor inhibition effect is a concentration dependent effect; although the mice of the 5-FU positive administration group showed higher tumor inhibiting activity, the mice had obvious side effects, which resulted in weight loss, decreased immune organ index, obvious decline of vitality and poor physiological condition (Table 6 and FIG. 11). Further, the results of statistical analysis of the tumor inhibition rates of different groups show that the tumor inhibition rate of the high-dose group of the Qihong polysaccharide KBPW on CT26 WT colorectal cancer tumor-bearing mice reaches 71.26 +/-4.34%, and the immune organ thymus index of the tumor-bearing mice can be obviously improved. The results show that the Qihong polysaccharide KBPW has good in vivo effect of resisting CT26 WT colorectal cancer, and the toxic and side effects are far smaller than those of the traditional antitumor drug 5-FU, so that the influence on the physiological state of mice is small, and adverse reactions are avoided after long-term use.
Table 6 inhibition of tumor growth in CT26 WT colorectal cancer tumor-bearing mice by Qihong polysaccharide KBPW1
Note that: the data in the table are **P<0.01,* P <0.05, representing a comparison with the model set; ##P<0.01,# P <0.05, indicating comparison with the normal group.
The above embodiments are only for illustrating the technical solution of the present invention, and are not limiting; although the invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical scheme described in the foregoing embodiments can be modified or some technical features thereof can be replaced by equivalents; such modifications and substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.
Claims (10)
1. A keemun polysaccharide KBPW with anti-tumor activity, wherein the repeatable primary structural unit of the keemun polysaccharide KBPW contains →4)-β-D-Glcp-(1→、α-L-Araf-(1→、→3)-β-D-Galp-(1→、→5)-α-L-Araf-(1→、→3,5)-β-L-Araf-(1→、β-D-Glcp-(1→、→4,6)-β-D-Glcp-(1→、→6)-β-D-Glcp-(1→ eight glycosidic linkages; the connection mode of the glycosidic bond is shown as formula 1:
2. The antitumor active muntin polysaccharide KBPW a 1 according to claim 1, wherein the muntin polysaccharide KBPW a has a relative molecular mass of 3.8x10 3 Da.
3. The antitumor active muntin polysaccharide KBPW a 1 according to claim 1, wherein said muntin polysaccharide KBPW a is composed of arabinose, galactose and glucose in a molar ratio of 2.62:1.02:6.36.
4. Use of a keemun polysaccharide KBPW1 with anti-tumor activity according to any one of claims 1-3 for the preparation of an anti-tumor medicament.
5. The use of claim 4, wherein the tumor comprises colorectal cancer (CRC), cholangiocarcinoma, gastric cancer, glioblastoma (GBM), leiomyosarcoma, melanoma, lung cancer, neuroblastoma (NB), ovarian cancer, pancreatic cancer, prostate cancer, thyroid cancer, breast cancer, or any combination thereof.
6. An antitumor pharmaceutical composition comprising the keemun polysaccharide KBPW1 having antitumor activity according to any one of claims 1 to 3.
7. The anti-tumor pharmaceutical composition according to claim 6, wherein the composition further comprises one or more pharmaceutically acceptable carriers.
8. The anti-tumor pharmaceutical composition according to claim 6, wherein the pharmaceutically acceptable carrier is a diluent, excipient, filler, binder, wetting agent, disintegrant, absorption enhancer, adsorption carrier, surfactant or lubricant.
9. The anti-tumor pharmaceutical composition according to claim 6, wherein the pharmaceutically acceptable carrier is a diluent.
10. The anti-tumor pharmaceutical composition according to claim 6, wherein the oral dosage form of the pharmaceutical composition comprises a tablet, a capsule, a lozenge, an oral liquid, a granule, a pill or a powder.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410402982.0A CN118085120A (en) | 2024-04-03 | 2024-04-03 | Qihong polysaccharide KBPW1 with anti-tumor activity and application thereof in preparation of anti-tumor drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202410402982.0A CN118085120A (en) | 2024-04-03 | 2024-04-03 | Qihong polysaccharide KBPW1 with anti-tumor activity and application thereof in preparation of anti-tumor drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN118085120A true CN118085120A (en) | 2024-05-28 |
Family
ID=91151763
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202410402982.0A Pending CN118085120A (en) | 2024-04-03 | 2024-04-03 | Qihong polysaccharide KBPW1 with anti-tumor activity and application thereof in preparation of anti-tumor drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN118085120A (en) |
-
2024
- 2024-04-03 CN CN202410402982.0A patent/CN118085120A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Pan et al. | Chemical structure and effects of antioxidation and against α-glucosidase of natural polysaccharide from Glycyrrhiza inflata Batalin | |
| Niu et al. | In Vitro Antioxidant activities and anti-diabetic effect of a polysaccharide from Schisandra sphenanthera in rats with type 2 diabetes | |
| Zhou et al. | Extraction, structural analysis and antioxidant activity of aloe polysaccharide | |
| WO2015090180A1 (en) | Sanchi flower arab galactan and preparation method and use thereof | |
| CN105859903B (en) | radix glehniae polysaccharide and preparation method and application thereof | |
| CN114751997B (en) | Yellow large tea polysaccharide with anti-inflammatory activity, preparation method and application thereof, and anti-inflammatory pharmaceutical composition | |
| CN114874344A (en) | Preparation method and application of alkali-extracted polysaccharide of highland barley tender leaves | |
| Zhang et al. | Preparation and structural characterization of acid-extracted polysaccharide from Grifola frondosa and antitumor activity on S180 tumor-bearing mice | |
| CN102161710A (en) | Method for preparing tremellan with low molecular weight and novel medicinal application thereof | |
| CN110452312B (en) | Dendrobium huoshanense polysaccharide with effect of resisting digestive system cancer | |
| CN106177187B (en) | Tea polyphenol tea polysaccharide composition with synergistic attenuation and anti-liver cancer effects | |
| Song et al. | Effects of solution behavior on polysaccharide structure and inhibitory of α-glucosidase activity from Cordyceps militaris | |
| CN109232756B (en) | Suaeda salsa polysaccharide extract and preparation method and application thereof | |
| CN118085120A (en) | Qihong polysaccharide KBPW1 with anti-tumor activity and application thereof in preparation of anti-tumor drugs | |
| CN118373923A (en) | Preparation method of Qihong polysaccharide KBPW with anti-tumor activity | |
| CN113024681B (en) | Polygonatum sibiricum galactan and preparation method and application thereof | |
| CN103059152B (en) | Isolates of hedysari polybotrys polysaccharide 3 and application thereof | |
| Tian et al. | Structural characterization, and in vitro hypoglycemic activity of a polysaccharide from the mushroom Cantharellus yunnanensis | |
| Lan et al. | Absorption and utilization of polysaccharides from Cordyceps militaris fruiting bodies and their protective effects against CCl4-induced acute liver injury in mice | |
| CN113651896B (en) | Bacteroides dychii extracellular polysaccharide and extraction method and application thereof | |
| Li et al. | Structure of Cardamine hupingshanensis No. 3 Polysaccharide (CHP‐3) and its Effect on Human Lung Cancer A549 Cells | |
| CN116640234B (en) | Pseudo-ginseng flower polysaccharide RN0D and preparation method and application thereof | |
| CN114316085B (en) | Cis-hyaluronan hexasaccharide and preparation method and application thereof | |
| CN114539441B (en) | Inonotus obliquus glucan and preparation method and application thereof | |
| CN116655820B (en) | Ampelopsis grossedentata acidic polysaccharide AGP-3a, extraction and separation method thereof and application thereof in preparation of anti-inflammatory cosmetics |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |