WO2022217763A1 - 一种硫酸化鲍鱼多糖及其在抑制新冠病毒中的应用 - Google Patents
一种硫酸化鲍鱼多糖及其在抑制新冠病毒中的应用 Download PDFInfo
- Publication number
- WO2022217763A1 WO2022217763A1 PCT/CN2021/104455 CN2021104455W WO2022217763A1 WO 2022217763 A1 WO2022217763 A1 WO 2022217763A1 CN 2021104455 W CN2021104455 W CN 2021104455W WO 2022217763 A1 WO2022217763 A1 WO 2022217763A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- sulfated
- abalone
- abalone polysaccharide
- polysaccharide
- cov
- Prior art date
Links
- 150000004676 glycans Chemical class 0.000 title claims abstract description 53
- 229920001282 polysaccharide Polymers 0.000 title claims abstract description 53
- 239000005017 polysaccharide Substances 0.000 title claims abstract description 53
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims abstract description 29
- 238000003756 stirring Methods 0.000 claims abstract description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000000502 dialysis Methods 0.000 claims abstract description 15
- 238000001816 cooling Methods 0.000 claims abstract description 9
- 239000000843 powder Substances 0.000 claims abstract description 9
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000002244 precipitate Substances 0.000 claims abstract description 7
- 238000004108 freeze drying Methods 0.000 claims abstract description 5
- 241000711573 Coronaviridae Species 0.000 claims description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 7
- 239000011229 interlayer Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 239000002706 dry binder Substances 0.000 claims description 4
- 229920000881 Modified starch Polymers 0.000 claims description 3
- 229920001525 carrageenan Polymers 0.000 claims description 3
- 235000010418 carrageenan Nutrition 0.000 claims description 3
- 239000000679 carrageenan Substances 0.000 claims description 3
- 229940113118 carrageenan Drugs 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229920002521 macromolecule Polymers 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims description 3
- 230000001954 sterilising effect Effects 0.000 claims description 2
- 238000004659 sterilization and disinfection Methods 0.000 claims description 2
- 238000001727 in vivo Methods 0.000 claims 1
- 241001678559 COVID-19 virus Species 0.000 abstract description 25
- 230000000694 effects Effects 0.000 abstract description 7
- 239000012374 esterification agent Substances 0.000 abstract description 7
- 238000001890 transfection Methods 0.000 abstract description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 230000007935 neutral effect Effects 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 241000700605 Viruses Species 0.000 description 12
- 208000025721 COVID-19 Diseases 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 9
- UFWWAKOWSBGGCP-UHFFFAOYSA-N pyridine;sulfurochloridic acid Chemical compound OS(Cl)(=O)=O.C1=CC=NC=C1 UFWWAKOWSBGGCP-UHFFFAOYSA-N 0.000 description 9
- 229940096437 Protein S Drugs 0.000 description 8
- 101710198474 Spike protein Proteins 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 102100035765 Angiotensin-converting enzyme 2 Human genes 0.000 description 6
- 108090000975 Angiotensin-converting enzyme 2 Proteins 0.000 description 6
- 241000282552 Chlorocebus aethiops Species 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 210000003292 kidney cell Anatomy 0.000 description 5
- 101000716700 Mesobuthus martensii Toxin BmKT Proteins 0.000 description 4
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 4
- 239000007850 fluorescent dye Substances 0.000 description 4
- 235000013376 functional food Nutrition 0.000 description 4
- 230000009545 invasion Effects 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 208000001528 Coronaviridae Infections Diseases 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
- 101000773743 Homo sapiens Angiotensin-converting enzyme Proteins 0.000 description 2
- 208000025370 Middle East respiratory syndrome Diseases 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- 230000002924 anti-infective effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
- 239000010931 gold Substances 0.000 description 2
- 229910052737 gold Inorganic materials 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000012827 research and development Methods 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 102000015427 Angiotensins Human genes 0.000 description 1
- 108010064733 Angiotensins Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000132012 Atractylodes Species 0.000 description 1
- 241000008904 Betacoronavirus Species 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-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
- 206010011878 Deafness Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 241000218671 Ephedra Species 0.000 description 1
- 208000015220 Febrile disease Diseases 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
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108060003393 Granulin Proteins 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
- 241000237852 Mollusca Species 0.000 description 1
- 108090001074 Nucleocapsid Proteins Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 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 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 108010051210 beta-Fructofuranosidase Proteins 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- ZCGNOVWYSGBHAU-UHFFFAOYSA-N favipiravir Chemical compound NC(=O)C1=NC(F)=CNC1=O ZCGNOVWYSGBHAU-UHFFFAOYSA-N 0.000 description 1
- 229950008454 favipiravir Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000012757 fluorescence staining Methods 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000010440 gypsum Substances 0.000 description 1
- 229910052602 gypsum Inorganic materials 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 235000011073 invertase Nutrition 0.000 description 1
- 239000001573 invertase Substances 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 231100000957 no side effect Toxicity 0.000 description 1
- 239000004745 nonwoven fabric Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- LXSYSTHQLOXIFU-UHFFFAOYSA-N phosphoric acid 2,2,2-trichloroacetaldehyde Chemical compound ClC(C=O)(Cl)Cl.P(O)(O)(O)=O LXSYSTHQLOXIFU-UHFFFAOYSA-N 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- 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
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/14—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings
- A01N43/16—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom six-membered rings with oxygen as the ring hetero atom
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/56—Materials from animals other than mammals
- A61K35/618—Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- the new coronavirus (SARS-CoV-2) is a newly discovered strain of coronavirus in the human body, and it is also the seventh known coronavirus that can infect the human body.
- the new coronary pneumonia (COVID-19) caused by SARS-CoV-2 is highly contagious and highly concealed, with a wide range of transmission routes, and its transmission speed is much higher than that of Middle East Respiratory Syndrome (MERS) and SARS (SARS). Afterwards, fever, cough, and difficulty breathing may result in severe acute respiratory syndrome or even death. So far, the development of specific anti-coronavirus drugs and related vaccines is still a very long and arduous process.
- the purpose of the present invention is to solve the problem of the lack of relevant functional foods and anti-COVID-19 medicines for the prevention and treatment of COVID-19 in the prior art.
- step S2 dissolve abalone crude polysaccharide freeze-dried powder in N,N-dimethylformamide at a ratio of 5-15:1, add it to the esterifying agent prepared in step S1, and stir at a constant temperature of 30-80 °C for reaction 1 -8h, cool to room temperature, add pre-cooled water in a ratio of 1:1-9;
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Wood Science & Technology (AREA)
- Dermatology (AREA)
- Environmental Sciences (AREA)
- Dentistry (AREA)
- Marine Sciences & Fisheries (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Plant Pathology (AREA)
- Polymers & Plastics (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供一种硫酸化鲍鱼多糖的制备方法，包括以下步骤：S1、冰浴中，将无水吡啶搅拌均匀，逐滴加入氯磺酸，得到酯化剂；S2、将鲍鱼粗多糖冻干粉溶于N,N-二甲基甲酰胺中，加入所述酯化剂中，30-80℃恒温搅拌反应1-8h，冷却至室温，加入预冷水；S3、调节pH值至中性，边搅拌边加入无水乙醇，静置后，离心取沉淀复溶于水，过滤后透析，冻干后即得硫酸化鲍鱼多糖。本发明硫酸化的鲍鱼多糖能够有效抑制新冠病毒对细胞的转染作用，对新冠病毒的抑制效果是普通鲍鱼多糖的3.3倍。
Description
本发明涉及免疫药物领域，更具体地说，涉及一种硫酸化鲍鱼多糖的制备及其在COVID-19抗感染药物及其功能食品、功能日用品的新应用。
新型冠状病毒(SARS-CoV-2)，是一种在人体内新发现的冠状病毒株，也是目前已知的第七种能够感染人体的冠状病毒。由SARS-CoV-2引起的新冠肺炎(COVID-19)具有高传染性和高隐蔽性，传播途径广泛，其传播速度远大于中东呼吸综合征(MERS)和非典(SARS)，人感染新冠肺炎后会发热咳嗽、呼吸困难，严重可导致急性呼吸综合征甚至死亡。迄今为止，针对抗新冠病毒特效药物和相关疫苗的研发仍旧是一个十分漫长并且艰巨的过程。中医药方面，张仲景所著的《伤寒杂病论》中记载表明“清肺排毒汤”可用于由寒邪引起的外感热病，临床应用于COVID-19的治疗有显著疗效，但是方剂中的一些成分例如麻黄、白术、藿香、生石膏等成分并不适用于体虚、胃寒等人，其它中药方剂例如《太平惠民和剂局方》中记载的“人参败毒散”、“化湿败毒方”等要求方剂炮制方法严谨考究，另一方面，中药调理需要长期服用，同时中药方剂成分复杂，无法探究人体吸收后起作用的具体成分，因此对于COVID-19的快速治疗存在局限作用。相对于传统的中医药而言，西药在治疗COVID-19方面也有应用，研究表明阿比多尔、法匹拉韦、磷酸氯醛等药物在早期预防和后期治疗方面有些疗效，但是其副作用较大，会引起呕吐腹泻、肝炎和视听力受损等，甚至在多年后对身体器官，例如心脏造成不可逆的伤害，与此同时，某些药物的使用也有局限性，对于孕妇、老人和儿童禁止服用。基于此，加快预防和治疗COVID-19的相关功能食品和抗COVID-19药物的研发势在必行。
SARS-CoV-2是β属的冠状病毒，由四种结构蛋白共同编码，包括刺突蛋白、核衣壳蛋白、基质蛋白和小蛋白。其中刺突蛋白(S)在冠状病毒传播中起着决定性作用，它位于病毒表面，由S1和S2两种亚基构成，S1亚基内部的受体结合区(RBD)可以和人血管紧张素转化酶Ⅱ(ACE2)特异性识别，同时，S2亚基能够完成细胞和病毒之间的融合，使SARS-CoV-2利用ACE2为载体进入到宿主，进而导致病毒的传播。
鲍鱼又名“海耳”，是一种鲍科鲍属的单壳软体动物，是名贵的“海珍品”之一，素有海洋“软黄金”的美誉，其富含有大量蛋白质和糖类，因此也被认为是“餐桌黄金，海珍之冠”。目前对于鲍鱼多糖结构解析表明，其主要由葡萄糖、半乳糖和甘露糖组成，并伴有少量岩藻糖和木糖等，而多糖作为一种生物大分子物质，近年来不断被证实具有抗肿瘤、抗氧化、增强机体免疫力、防止动脉粥样硬化等多重生物活性，对后续功能食品、日用品和药物的研发指明了新方向。
发明内容
本发明的目的是解决现有技术缺乏预防和治疗COVID-19的相关功能食品和抗COVID-19药物的问题。
为了实现上述目的，本发明提供一种硫酸化鲍鱼多糖的制备方法，包括以下步骤：
S1、冰浴中，将无水吡啶搅拌均匀，冷却至1-10℃，1-9:1的比例逐滴加入氯磺酸，得到酯化剂；
S2、按5-15:1的比例将鲍鱼粗多糖冻干粉溶于N,N-二甲基甲酰胺中，加入步骤S1制备的所述酯化剂中，30-80℃恒温搅拌反应1-8h，冷却至室温，按1:1-9的比例加入预冷水；
S3、调节pH值至中性，边搅拌边加入1-5倍体积的无水乙醇，静置10-30h后，在3000-8000转/分条件下，离心取沉淀复溶于水，过滤后经透析、冻干，即得硫酸化鲍鱼多糖。
优选的，步骤S3中所述透析使用1-10kDa透析袋。
优选的，所述硫酸化鲍鱼多糖在40-70℃条件下烘干，与干粘合剂搅拌混合均匀后，压制成固体。
优选的，所述干粘合剂包括预胶化淀粉。
优选的，所述硫酸化鲍鱼多糖和亲水性高分子物质共溶于水，灭菌并冷却后，冷冻干燥使水分低于1-10％形成网状结构，制成抗新冠病毒夹层。
优选的，所述亲水性高分子物质包括卡拉胶。
一种硫酸化鲍鱼多糖的应用，用于抑制新冠病毒。
优选的，用于抑制体内的新冠病毒。
优选的，用于抑制空气中的新冠病毒。
优选的，用于吸附新冠病毒。
本申请的有益效果是：
本申请通过优化氯磺酸-吡啶法中的反应条件来制备硫酸化修饰的鲍鱼多糖，制备的硫酸化鲍鱼多糖与300FFU(病灶形成单位)的SARS-CoV-2于37℃共培养30分钟，接种在非洲绿猴肾细胞(Vero E6)中孵育24小时，以新冠肺炎恢复者的血清作为一抗，以Alexa
488人IgG为二抗，经DAPI(4',6-二脒基-2-苯基吲哚)染料染色后于显微镜下观察，发现SARS-CoV-2的细胞数目明显减少，本发明方法硫酸化的鲍鱼多糖对SARS-CoV-2的抑制效果是普通鲍鱼多糖的3.3倍。
通过产物与病毒刺突蛋白和人血管紧张素转化酶Ⅱ的共同作用表明，所述硫酸化修饰的鲍鱼多糖能够阻碍二者的结合，同时将其应用于细胞实验中，结果显示，显著观察到其抑制SARS-CoV-2对非洲绿猴肾细胞的转染作用。
本制备发明的硫酸化鲍鱼多糖应用于抗SARS-CoV-2对人感染具有明显优势，可以有效阻碍刺突蛋白和人血管紧张素转化酶Ⅱ之间的特异性识别，使细胞和病毒之间的融合通道受阻，从而发挥抑制SARS-CoV-2传播的作用。硫酸化鲍鱼多糖作为经过修饰的食物来源产物，对人体无毒副作用等副反应。并且物质来源稳定易得，作为抑制和治疗新冠病毒对人体的感染效果显著，因而相比其他药物有显著优势。
图1是本发明加入病毒后与非洲绿猴肾细胞(Vero E6)共培养12小时后的荧光染色结果；
图2是鲍鱼多糖(AGSP)加入病毒后与非洲绿猴肾细胞(Vero E6)共培养12小时后的荧光染色结果；
图3是图1、2中SARS-CoV-2病毒荧光染色的相对定量结果。
制备鲍鱼粗多糖冻干粉可以选用大连鲍、皱纹盘鲍、杂色鲍等。
实施例1
将带有搅拌和冷凝装置的250mL三颈烧瓶置冰浴中，加入20mL无水吡啶，磁力搅拌均匀，充分冷却至10℃后，按设定的氯磺酸-吡啶1:3的比例逐滴加入 氯磺酸(平均0.23ml/min，即13秒1滴)，于30min内加完。称取180mg鲍鱼粗多糖冻干粉，溶于15ml的N,N-二甲基甲酰胺(DMF)中，加入上述加有酯化剂氯磺酸-吡啶的三颈烧瓶中，50℃恒温搅拌反应2h，冷却至室温后，按1:1-9的比例加入预冷的95ml冰纯净水，并用氢氧化钠溶液中和至中性，边搅拌边加入3倍体积的无水乙醇，静置20h后，在4000转/分条件下，离心15min取沉淀复溶于水，过滤，装入7000Da透析袋透析，冻干即得硫酸化修饰的鲍鱼多糖。通过实验发现能够阻碍ACE2与刺突蛋白的结合，并发现抑制了病毒分子侵入细胞。上述硫酸化修饰的鲍鱼多糖粉末在50℃条件下烘干，与药学上可用的辅料，即干粘合剂——预胶化淀粉搅拌混合均匀后，放入压片机，制成片状固体，口服后经过血液循环后在机体内部发挥其生物疗效，不会对机体产生严重的毒副作用，可以抑制体内的新冠病毒。
实施例2
将带有搅拌和冷凝装置的250mL三颈烧瓶置冰浴中，加入25mL无水吡啶，磁力搅拌均匀，充分冷却至1℃后，按设定的氯磺酸-吡啶1:5的比例逐滴加入氯磺酸(平均0.13ml/min，即23秒1滴)，于40min内加完。称取200mg鲍鱼粗多糖冻干粉，溶于20ml的N,N-二甲基甲酰胺(DMF)中，加入上述加有酯化剂氯磺酸-吡啶的三颈烧瓶中，60℃恒温搅拌反应4h，冷却至室温后，按1:1-9的比例加入预冷的100ml冰纯净水，并用氢氧化钠溶液中和至中性，边搅拌边加入3倍体积的无水乙醇，静置24h后，在4000转/分条件下，离心20min取沉淀复溶于水，过滤，装入7000Da透析袋透析，冻干即得硫酸化修饰的鲍鱼多糖。通过实验发现能够阻碍ACE2与刺突蛋白的结合，并发现抑制了病毒分子侵入细胞。硫酸化修饰的鲍鱼多糖制作成医用口罩的抗病毒夹层，将硫酸化修饰的鲍鱼多糖和亲水性高分子物质卡拉胶共溶于水，灭菌并冷却后倒入模具中，冷冻干燥使水分低于10％形成网状结构，在所述抗病毒夹层内外分别用医用无纺布缝合。上述硫酸化修饰的鲍鱼多糖应用在口罩夹层中，可以有效将新冠病毒截留并吸附，防止新冠病毒通过呼吸道传播进入人体。
实施例3
将带有搅拌和冷凝装置的250mL三颈烧瓶置冰浴中，加入20mL无水吡啶，磁力搅拌均匀，充分冷却至1℃后，按设定的氯磺酸-吡啶1:4的比例逐滴加入氯磺酸(平均0.15ml/min，即20秒1滴)，于35min内加完。称取200mg鲍鱼粗多糖冻干粉，溶于25ml N,N-二甲基甲酰胺(DMF)中，加入上述加有酯化剂氯磺酸-吡啶的三颈烧瓶中，70℃恒温搅拌反应7h，冷却至室温后，按1:1-9的比 例加入预冷的90ml冰纯净水，并用氢氧化钠溶液中和至中性，边搅拌边加入3倍体积的无水乙醇，静置24h后，在4000转/分条件下，离心15min取沉淀复溶于水，过滤，装入3500Da透析袋透析，冻干即得硫酸化修饰的鲍鱼多糖。通过实验发现能够阻碍ACE2与刺突蛋白的结合，并发现抑制了病毒分子侵入细胞。如附图1-3所示，将上述硫酸化修饰的鲍鱼多糖与非洲绿猴肾细胞(Vero E6)共培养12小时后，经过免疫荧光染色发现，可以显著抑制SARS-CoV-2对Vero E6的侵染。其中，绿色代表SARS-CoV-2病毒荧光染色结果；蓝色代表DAPI对活Vero E6细胞DNA的染色结果。图1中绿色代表SARS-CoV-2，蓝色代表Vero E6，随着S-AGSP浓度的升高，SARS-CoV-2所占比例下降明显，证明S-AGSP对于SARS-CoV-2病毒有明显抑制作用。图2中绿色代表SARS-CoV-2，蓝色代表Vero E6，随着AGSP浓度的升高，SARS-CoV-2所占比例并无太大改变。空白对照组中SARS-CoV-2比例为0.77，加入30μg/ml的S-AGSP后，SARS-CoV-2比例降低为0.54；空白对照组中SARS-CoV-2比例为0.75，加入30μg/ml的AGSP后，SARS-CoV-2比例为0.70。图3是SARS-CoV-2病毒荧光染色的相对定量结果，结果表明随着S-AGSP浓度的升高，病毒释放量逐渐降低；随着AGSP浓度的升高，病毒释放量相对于空白对照组有所降低数值但总体均高于S-AGSP，因此证明S-AGSP可用于抑制新冠病毒。
上述硫酸化多糖溶于纯净水混匀后，分装于喷雾瓶/壶中，可以制作成喷雾，用于物品表面消毒，抑制COVID-19在空气中的传播，从而防止新冠病毒进入人体。
实施例4
将带有搅拌和冷凝装置的250mL三颈烧瓶置冰浴中，加入25mL无水吡啶，磁力搅拌均匀，充分冷却后，按设定的氯磺酸-吡啶1:6的比例逐滴加入氯磺酸，于40min内加完。称取220mg鲍鱼粗多糖冻干粉，溶于20ml的N,N-二甲基甲酰胺(DMF)中，加入上述加有酯化剂氯磺酸-吡啶的三颈烧瓶中，65℃恒温搅拌反应3.5h，冷却至室温后，加入预冷的85ml冰水，并用氢氧化钠溶液中和至中性，边搅拌边加入3倍体积的无水乙醇，静置24h后，在4000转/分条件下，离心15min取沉淀复溶于水，过滤，装入1000Da透析袋透析，冻干即得硫酸化修饰的鲍鱼多糖。通过实验发现能够阻碍ACE2与刺突蛋白的结合，并发现抑制了病毒分子侵入细胞。基于此，本申请所述的硫酸化修饰的鲍鱼多糖可以作为特殊的一种功能性物质添加到日常食用的休闲食品中，对于COVID-19起到早起预防的作用，对轻症状病人也能起到抑制病情进一步发展的作用。
综上所述，本发明制备的硫酸化的鲍鱼多糖可以制备成抗感染药物，如胶囊、片剂、丸剂、颗粒剂、注射剂等；可以经过静脉注射、肌肉注射或者口服等途径进行给药；还可以制作成防护用品，如湿巾、口罩夹层填充物、喷雾等。
以上所述，仅为本发明较佳的具体实施方式，但本发明的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明披露的技术范围内，根据本发明的技术方案及其发明构思加以等同替换或改变，都应涵盖在本发明的保护范围之内。
Claims (10)
- 一种硫酸化鲍鱼多糖的制备方法，其特征在于，包括以下步骤：S1、冰浴中，将无水吡啶搅拌均匀，冷却至1-10℃，按1-9:1的比例逐滴加入氯磺酸，得到酯化剂；S2、按5-15:1的比例将鲍鱼粗多糖冻干粉溶于N,N-二甲基甲酰胺中，加入步骤S1制备的所述酯化剂中，30-80℃恒温搅拌反应1-8h，冷却至室温，按1:1-9的比例加入预冷水；S3、调节pH值至中性，边搅拌边加入1-5倍体积的无水乙醇，静置10-30h后，在3000-8000转/分条件下，离心取沉淀复溶于水，过滤后经透析、冻干，即得硫酸化鲍鱼多糖。
- 根据权利要求1所述硫酸化鲍鱼多糖的制备方法，其特征在于，步骤S1中所述氯磺酸逐滴加入的速度为13-23秒/滴；步骤S3中所述透析使用1-10kDa透析袋。
- 根据权利要求1所述硫酸化鲍鱼多糖的制备方法，其特征在于，所述硫酸化鲍鱼多糖在40-70℃条件下烘干，与干粘合剂搅拌混合均匀后，压制成固体。
- 根据权利要求3所述硫酸化鲍鱼多糖的制备方法，其特征在于，所述干粘合剂包括预胶化淀粉。
- 根据权利要求1所述硫酸化鲍鱼多糖的制备方法，其特征在于，所述硫酸化鲍鱼多糖和亲水性高分子物质共溶于水，灭菌并冷却后，冷冻干燥使水分低于1-10％形成网状结构，制成抗新冠病毒夹层。
- 根据权利要求5所述硫酸化鲍鱼多糖的制备方法，其特征在于，所述亲水性高分子物质包括卡拉胶。
- 一种硫酸化鲍鱼多糖的应用，其特征在于，用于抑制新冠病毒。
- 根据权利要求7所述的硫酸化鲍鱼多糖的应用，其特征在于，用于抑制体内的新冠病毒。
- 根据权利要求7所述的硫酸化鲍鱼多糖的应用，其特征在于，用于抑制空气中的新冠病毒。
- 根据权利要求7所述的硫酸化鲍鱼多糖的应用，其特征在于，用于吸附新冠病毒。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110401445.0A CN113150178B (zh) | 2021-04-14 | 2021-04-14 | 一种硫酸化鲍鱼多糖及其在抑制新冠病毒中的应用 |
| CN202110401445.0 | 2021-04-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2022217763A1 true WO2022217763A1 (zh) | 2022-10-20 |
Family
ID=76890464
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CN2021/104455 WO2022217763A1 (zh) | 2021-04-14 | 2021-07-05 | 一种硫酸化鲍鱼多糖及其在抑制新冠病毒中的应用 |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN113150178B (zh) |
| WO (1) | WO2022217763A1 (zh) |
Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008266265A (ja) * | 2007-04-24 | 2008-11-06 | Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho | 抗ウイルス剤 |
| CN103739733A (zh) * | 2014-01-09 | 2014-04-23 | 南京农业大学 | 一种抗鸭病毒性肝炎山豆根多糖及其分子修饰物 |
| CN104558228A (zh) * | 2014-12-30 | 2015-04-29 | 大连工业大学 | 一种制备鲍鱼硫酸多糖的方法 |
| CN110041442A (zh) * | 2018-12-29 | 2019-07-23 | 中港（福建）水产食品有限公司 | 一种鲍鱼壳抗氧化性水溶性多糖提取方法 |
| CN111454376A (zh) * | 2020-05-19 | 2020-07-28 | 爱礼康生物医药（苏州）有限公司 | 一种凤仙花聚糖、提取方法及在制备抗SARS-CoV-2药物中的应用 |
| CN111560080A (zh) * | 2020-05-19 | 2020-08-21 | 爱礼康生物医药（苏州）有限公司 | 半枝莲聚糖、提取方法及在制备抗SARS-CoV-2药物中的应用 |
| CN111588732A (zh) * | 2020-06-18 | 2020-08-28 | 大连工业大学 | 岩藻多糖在抗新型冠状病毒中的应用 |
| CN111658664A (zh) * | 2020-06-18 | 2020-09-15 | 大连工业大学 | 海参多糖在抗新型冠状病毒中的应用 |
| CN111773240A (zh) * | 2020-08-17 | 2020-10-16 | 中国海洋大学 | 海洋生物来源天然硫酸多糖在作为抗冠状病毒及所致疾病药物中的应用 |
| CN111803515A (zh) * | 2020-07-23 | 2020-10-23 | 广东工业大学 | 海藻多糖及其衍生物在制备预防和/或治疗新型冠状病毒感染药物中的应用 |
| CN112220799A (zh) * | 2020-11-02 | 2021-01-15 | 江苏泰德医药有限公司 | 一种抑制病毒的产品及用途 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100336831C (zh) * | 2005-10-11 | 2007-09-12 | 大连轻工业学院 | 鲍鱼多糖的提取方法 |
| CN102140141B (zh) * | 2011-05-13 | 2012-10-03 | 陈锦权 | 鲍鱼多糖的制备工艺 |
| CN108424468A (zh) * | 2018-02-06 | 2018-08-21 | 浦江县昂宝生物技术有限公司 | 一种鲍鱼多糖的制备工艺 |
-
2021
- 2021-04-14 CN CN202110401445.0A patent/CN113150178B/zh active Active
- 2021-07-05 WO PCT/CN2021/104455 patent/WO2022217763A1/zh active Application Filing
Patent Citations (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008266265A (ja) * | 2007-04-24 | 2008-11-06 | Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho | 抗ウイルス剤 |
| CN103739733A (zh) * | 2014-01-09 | 2014-04-23 | 南京农业大学 | 一种抗鸭病毒性肝炎山豆根多糖及其分子修饰物 |
| CN104558228A (zh) * | 2014-12-30 | 2015-04-29 | 大连工业大学 | 一种制备鲍鱼硫酸多糖的方法 |
| CN110041442A (zh) * | 2018-12-29 | 2019-07-23 | 中港（福建）水产食品有限公司 | 一种鲍鱼壳抗氧化性水溶性多糖提取方法 |
| CN111454376A (zh) * | 2020-05-19 | 2020-07-28 | 爱礼康生物医药（苏州）有限公司 | 一种凤仙花聚糖、提取方法及在制备抗SARS-CoV-2药物中的应用 |
| CN111560080A (zh) * | 2020-05-19 | 2020-08-21 | 爱礼康生物医药（苏州）有限公司 | 半枝莲聚糖、提取方法及在制备抗SARS-CoV-2药物中的应用 |
| CN111588732A (zh) * | 2020-06-18 | 2020-08-28 | 大连工业大学 | 岩藻多糖在抗新型冠状病毒中的应用 |
| CN111658664A (zh) * | 2020-06-18 | 2020-09-15 | 大连工业大学 | 海参多糖在抗新型冠状病毒中的应用 |
| CN111803515A (zh) * | 2020-07-23 | 2020-10-23 | 广东工业大学 | 海藻多糖及其衍生物在制备预防和/或治疗新型冠状病毒感染药物中的应用 |
| CN111773240A (zh) * | 2020-08-17 | 2020-10-16 | 中国海洋大学 | 海洋生物来源天然硫酸多糖在作为抗冠状病毒及所致疾病药物中的应用 |
| CN112220799A (zh) * | 2020-11-02 | 2021-01-15 | 江苏泰德医药有限公司 | 一种抑制病毒的产品及用途 |
Non-Patent Citations (5)
| Title |
|---|
| LIU, YILI; DUAN MENGMENG; SUN XIAONA; JIANG PINGRUI; SONG SHUANG: "Effect of Sulfate Group in Polysaccharide of Pacific Abalone on High Fat Diet-Induced Metabolic Syndrome in Mice", ABSTRACTS OF FOOD SUMMIT IN CHINA 2019 & 16TH ANNUAL MEETING OF CIFST; WUHAN, CHINA; NOVEMBER 13, 2019, 30 November 2019 (2019-11-30), pages 155 - 156, XP009541869 * |
| PAUL S. KWON, HANSEUL OH, SEOK-JOON KWON, WEIHUA JIN, FUMING ZHANG, KEITH FRASER, JUNG JOO HONG, ROBERT J. LINHARDT, JONATHAN S. D: "Sulfated polysaccharides effectively inhibit SARS-CoV-2 in vitro", CELL DISCOVERY, vol. 6, no. 1, 1 December 2020 (2020-12-01), XP055758214, DOI: 10.1038/s41421-020-00192-8 * |
| SHUANG SONG, HAORAN PENG, QINGLING WANG, ZHENGQI LIU, XIUPING DONG, CHENGRONG WEN, CHUNQING AI, YUJIAO ZHANG, ZHONGFU WANG, BEIWEI: "Inhibitory activities of marine sulfated polysaccharides against SARS-CoV-2", FOOD & FUNCTION, R S C PUBLICATIONS, GB, vol. 11, no. 9, 23 September 2020 (2020-09-23), GB , pages 7415 - 7420, XP055758218, ISSN: 2042-6496, DOI: 10.1039/D0FO02017F * |
| WANG ZHIJUN, XIE JIANHUA, SHEN MINGYUE, NIE SHAOPING, XIE MINGYONG: "Sulfated modification of polysaccharides: Synthesis, characterization and bioactivities", TRENDS IN FOOD SCIENCE & TECHNOLOGY, ELSEVIER SCIENCE PUBLISHERS, GB, vol. 74, 1 April 2018 (2018-04-01), GB , pages 147 - 157, XP055976973, ISSN: 0924-2244, DOI: 10.1016/j.tifs.2018.02.010 * |
| YIM SUNG-KUN, KIM KIAN, KIM INHEE, CHUN SANGHO, OH TAEHWAN, KIM JIN-UNG, KIM JUNGWON, JUNG WOOHUK, MOON HOSANG, KU BOSUNG, JUNG KY: "Inhibition of SARS-CoV-2 Virus Entry by the Crude Polysaccharides of Seaweeds and Abalone Viscera In Vitro", MARINE DRUGS, vol. 19, no. 4, pages 219, XP055844460, DOI: 10.3390/md19040219 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113150178B (zh) | 2023-05-02 |
| CN113150178A (zh) | 2021-07-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20180078508A1 (en) | Oncolytic virus formulation and preparation method thereof | |
| CN103040860A (zh) | 一种启动哺乳动物干细胞的方法及二氧化氯在制备用于启动哺乳动物干细胞的药物的应用 | |
| JP2012504150A5 (zh) | ||
| JP2012504150A (ja) | 生体活性材料をカプセル化したナノスフェアおよびナノスフェアの製剤化のための方法 | |
| CN107530310A (zh) | 柠檬酸铁在治疗缺铁性贫血中的用途 | |
| CN107488235A (zh) | 一种新的增强型抗原联合多肽诱导肝癌特异性ctl细胞的制备及应用 | |
| KR20070008089A (ko) | 댕댕이나무 추출물을 포함하는 간 질환 예방 및 치료효과를 가지는 약제학적 조성물 | |
| WO2022217763A1 (zh) | 一种硫酸化鲍鱼多糖及其在抑制新冠病毒中的应用 | |
| CN109674866A (zh) | 一种抗胃肠癌药物组合物、制备方法及其应用 | |
| CN109512854A (zh) | 用于预防和治疗过敏性鼻炎的益生菌组合物及基于其的鼻用制剂和制备方法 | |
| WO2007124625A1 (fr) | Polysaccharides de limace, procédé de production et utilisation de ceux-ci | |
| Gupta et al. | Preliminary pharmacokinetics and safety in healthy volunteers of VIR-3434, a monoclonal antibody for the treatment of chronic hepatitis B infection | |
| CN102988461A (zh) | 一种红景天注射液及其制备方法 | |
| JP2023522213A (ja) | 再生非ステロイド性抗炎症組成物、その生産方法、及び使用方法 | |
| AU737861B2 (en) | Remedies for AIDS | |
| CN106539979A (zh) | 一种治疗过敏性鼻炎的中药制剂 | |
| WO2011103794A1 (zh) | 用于治疗人乳头瘤病毒感染引起的疾病的喷剂及其制备方法 | |
| CN105147722A (zh) | 硫酸化白芨多糖的新用途及一种治疗眼表损伤的制剂 | |
| CN114917227B (zh) | 依伐卡托在制备抗蜱传脑炎病毒、西尼罗病毒、黄热病毒和基孔肯雅热病毒感染药中的应用 | |
| JP2855283B2 (ja) | 抗潰瘍剤およびその製造法 | |
| CN109700823A (zh) | 泰利霉素在抗埃博拉病毒感染中的应用 | |
| CN101686993A (zh) | 卡介菌多糖核酸提取物在制备治疗病毒性皮肤病的药物中的应用及其注射剂和制备方法 | |
| CN114344284A (zh) | 一种蛛丝载药口腔缓释膜的制备方法及应用 | |
| RU2790223C2 (ru) | Композиции и способы защиты от взвешенных в воздухе патогенов и раздражающих веществ | |
| CN117547519A (zh) | 一种基于sting激动剂的淋巴结靶向纳米粒及其制备方法和应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21936635 Country of ref document: EP Kind code of ref document: A1 |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 21936635 Country of ref document: EP Kind code of ref document: A1 |