CN115531427A - 槐耳或其提取物在制备抗流感病毒药物中的应用 - Google Patents
槐耳或其提取物在制备抗流感病毒药物中的应用 Download PDFInfo
- Publication number
- CN115531427A CN115531427A CN202211374301.1A CN202211374301A CN115531427A CN 115531427 A CN115531427 A CN 115531427A CN 202211374301 A CN202211374301 A CN 202211374301A CN 115531427 A CN115531427 A CN 115531427A
- Authority
- CN
- China
- Prior art keywords
- extract
- ear
- influenza virus
- pagodatree
- sophora japonica
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000284 extract Substances 0.000 title claims abstract description 73
- 244000046101 Sophora japonica Species 0.000 title claims abstract description 39
- 235000010586 Sophora japonica Nutrition 0.000 title claims abstract description 39
- 239000003814 drug Substances 0.000 title claims abstract description 34
- 241000700605 Viruses Species 0.000 title description 7
- 206010022000 influenza Diseases 0.000 title description 3
- 235000003417 Plumeria rubra f acutifolia Nutrition 0.000 claims abstract description 36
- 244000040691 Plumeria rubra f. acutifolia Species 0.000 claims abstract description 36
- 241000712461 unidentified influenza virus Species 0.000 claims abstract description 33
- 201000010099 disease Diseases 0.000 claims abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
- 230000009385 viral infection Effects 0.000 claims abstract description 10
- 210000005069 ears Anatomy 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 241000628997 Flos Species 0.000 claims abstract description 3
- 239000003112 inhibitor Substances 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 90
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
- 241000233866 Fungi Species 0.000 claims description 26
- 229920001282 polysaccharide Polymers 0.000 claims description 25
- 239000005017 polysaccharide Substances 0.000 claims description 25
- 150000004676 glycans Chemical class 0.000 claims description 24
- 239000000706 filtrate Substances 0.000 claims description 20
- 230000002829 reductive effect Effects 0.000 claims description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 241000219784 Sophora Species 0.000 claims description 10
- 239000000401 methanolic extract Substances 0.000 claims description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 239000003480 eluent Substances 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 108090000623 proteins and genes Proteins 0.000 claims description 7
- 102000004169 proteins and genes Human genes 0.000 claims description 6
- 241000221377 Auricularia Species 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 4
- 239000003208 petroleum Substances 0.000 claims description 4
- 239000000049 pigment Substances 0.000 claims description 4
- 238000010898 silica gel chromatography Methods 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 3
- 230000001376 precipitating effect Effects 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 238000000967 suction filtration Methods 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000006286 aqueous extract Substances 0.000 claims 1
- 229940124393 anti-influenza virus drug Drugs 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 22
- 210000004072 lung Anatomy 0.000 description 16
- 230000014509 gene expression Effects 0.000 description 13
- 239000000243 solution Substances 0.000 description 12
- PGZUMBJQJWIWGJ-ONAKXNSWSA-N oseltamivir phosphate Chemical group OP(O)(O)=O.CCOC(=O)C1=C[C@@H](OC(CC)CC)[C@H](NC(C)=O)[C@@H](N)C1 PGZUMBJQJWIWGJ-ONAKXNSWSA-N 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 8
- 102000004889 Interleukin-6 Human genes 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 5
- 102100037850 Interferon gamma Human genes 0.000 description 5
- 108010074328 Interferon-gamma Proteins 0.000 description 5
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 5
- 230000003247 decreasing effect Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 238000008157 ELISA kit Methods 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 241000712431 Influenza A virus Species 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 201000007270 liver cancer Diseases 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 210000000952 spleen Anatomy 0.000 description 3
- 210000001541 thymus gland Anatomy 0.000 description 3
- 230000003612 virological effect Effects 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- 241000221198 Basidiomycota Species 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 241000222341 Polyporaceae Species 0.000 description 2
- 241000701093 Suid alphaherpesvirus 1 Species 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 201000010740 swine influenza Diseases 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000002255 vaccination Methods 0.000 description 2
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 description 1
- 241000009794 Agaricomycetes Species 0.000 description 1
- 208000031648 Body Weight Changes Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000713196 Influenza B virus Species 0.000 description 1
- 241000713297 Influenza C virus Species 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 241000222383 Polyporales Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000044209 Tumor Suppressor Genes Human genes 0.000 description 1
- 108700025716 Tumor Suppressor Genes Proteins 0.000 description 1
- 241001517075 Vanderbylia Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000004579 body weight change Effects 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229960002194 oseltamivir phosphate Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 208000026425 severe pneumonia Diseases 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 229940061367 tamiflu Drugs 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/07—Basidiomycota, e.g. Cryptococcus
-
- 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
-
- 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
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- 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
- C08B37/0003—General processes for their isolation or fractionation, e.g. purification or extraction from biomass
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Botany (AREA)
- Pulmonology (AREA)
- Microbiology (AREA)
- Medical Informatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Alternative & Traditional Medicine (AREA)
- Sustainable Development (AREA)
- Biochemistry (AREA)
- Materials Engineering (AREA)
- Polymers & Plastics (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
本发明公开了槐耳或其提取物在制备抗流感病毒药物中的应用。本发明提供了槐耳或其提取物的应用,所述应用为:槐耳或其提取物在制备治疗流感病毒所致疾病的药物中的应用;槐耳或其提取物在制备治疗流感病毒感染的药物中的应用;槐耳或其提取物在制备预防流感病毒所致疾病的药物中的应用;槐耳或其提取物在制备预防流感病毒感染的药物中的应用;槐耳或其提取物在制备流感病毒抑制剂中的应用。本发明提供了槐耳或其提取物作为流感病毒药物的新用途,实现了抗击流感病毒药物制备的新思路。
Description
技术领域
本发明涉及生物技术领域,具体为槐耳或其提取物在制备抗流感病毒药物中的应用。
背景技术
药用真菌作为天然药物资源中极为重要的组成部分,已经发展成为当今探索和发掘新药的一个重要领域。槐耳是重要的药用真菌,隶属于担子菌门(Basidiomycetes)、伞菌纲(Agaricomycetes)、多孔菌目(Polyporales)、多孔菌科(Polyporaceae,Vanderbylia)属,其入药史可追溯到公元3世纪葛洪的《肘后方》到明朝的《本草纲目》,别名“槐生拜尔孔菌”、“槐菌”、“槐蛾”等,其味苦辛,性平无毒,有“治风”、“破血”、“益力”的功效。现代药理研究表明,槐耳可以通过抑制肿瘤细胞的生长与增殖、诱导肿瘤细胞凋亡、抑制血管新生、抑制肿瘤细胞侵袭与转移、调节多种癌基因与抑癌基因的表达、提高机体免疫力、逆转肿瘤细胞的耐药性等多种途径发挥抗肿瘤作用。其单味药物及提取物作为癌症辅助治疗药物于1997年在我国获批上市,商品名为“金克”(槐耳颗粒),用于原发性肝癌的治疗。2018年,由陈孝平院士主导的一项涉及全国39个医疗中心和1044名患者的随机临床试验表明槐耳颗粒能使肝癌术后复发率降低33%,证实了槐耳颗粒作为一种肝癌术后辅助治疗药物的有效性。
流感病毒主要分为三大类,分别是甲型流病毒、乙型流病毒和丙型流感病毒。其中甲型流感病毒变异最快,传染性最强,很容易引起大范围的流行,而且症状也比较严重。甲型流感病毒常见的有H1N1、H3N2、H7N9亚型。21世纪以来世界范围内连续爆发了多次流感病毒疫情,2009年爆发H1N1病毒传播的是近年来最严重的病例之一。目前,大多数流感病毒是季节性传播的。治疗流感病毒最有效的方法是接种疫苗。但病毒的强变异能力导致逐年需要接种疫苗,给人们带来极大的不便。
中国专利号为CN113648324B公开了槐耳多糖在防治猪伪狂犬病病毒中的应用,但流感病毒与猪伪狂犬病病毒不管从病毒本身还是作用对象都存在巨大差异。
发明内容
本发明的目的是提供槐耳或其提取物在制备抗流感病毒药物中的应用。
本发明提供了槐耳或其提取物的应用,所述应用为以下(a1)和/或(a2)和/或(a3)和/或(a4)和/或(a5):
(a1)槐耳或其提取物在制备治疗流感病毒所致疾病的药物中的应用;
(a2)槐耳或其提取物在制备治疗流感病毒感染的药物中的应用;
(a2)槐耳或其提取物在制备预防流感病毒所致疾病的药物中的应用;
(a2)槐耳或其提取物在制备预防流感病毒感染的药物中的应用;
(a2)槐耳或其提取物在制备流感病毒抑制剂中的应用。
进一步的,槐耳提取物为槐耳水提取物和/或槐耳醇提取物。
本发明还提供了一种药物,其活性成分包括槐耳或其提取物;
所述药物的功能为以下(b1)和/或(b2)和/或(b3)和/或(b4):
(b1)治疗流感病毒所致疾病;
(b2)治疗流感病毒感染;
(b3)预防流感病毒所致疾病;
(b4)预防流感病毒感染
进一步的,槐耳提取物为槐耳水提取物和/或槐耳醇提取物。
本发明还提供了槐耳提取物的制备方法,包括如下操作:
(一)乙醇溶液提取槐耳得到抽滤液,减压浓缩所述抽滤液得到浸膏,将所述浸膏进行硅胶色谱层析,依次用石油醚、二氯甲烷、乙酸乙酯、50%甲醇洗脱,得到甲醇洗脱液,减压浓缩所述甲醇洗脱液至浸膏剂,干燥所述浸膏剂至恒重,得到槐耳甲醇提取物;和/或
(二)乙醇溶液回流提取槐耳并去除槐耳的色素,分离药渣后纯水浓缩提取得到浓缩提取液,用乙醇沉淀所述浓缩提取液,然后除蛋白得到槐耳多糖提取物。
进一步的,所述操作(一)中乙醇溶液提取槐耳得到抽滤液的操作具体包括:以10倍量的70%乙醇溶液超声提取槐耳粉末35分钟,提取次数为3次,每次抽滤均分离出药渣,合并第一次抽滤液、第二次抽滤液和第三次抽滤液,得到所述抽滤液。
进一步的,所述操作(一)中干燥所述浸膏剂至恒重的操作具体包括:真空干燥所述浸膏剂,得到所述槐耳甲醇提取物。
进一步的,所述操作(二)中分离药渣后纯水浓缩提取得到浓缩提取液的操作具体包括:分离药渣后以15倍量纯水煎煮提取三次,每次2小时,得到所述浓缩提取液。
本发明的发明人制备了槐耳提取物并检测了其对于流感病毒的抗病毒效果。结果表明,槐耳能够对机体的炎症水平有一定的调节作用,具有较好的抗病毒效果。本发明提供了槐耳或其提取物作为流感病毒药物的新用途,实现了抗击流感病毒药物制备的新思路。
附图说明
通过阅读下文优选实施方式的详细描述,本申请的方案和优点对于本领域普通技术人员将变得清楚明了。附图仅用于示出优选实施方式的目的,而并不认为是对本发明的限制。
在附图中:
图1为实施例中不同实验组中小鼠的肺指数统计图;
图2为实施例中不同实验组中小鼠的体重变化统计图;
图3为实施例中不同实验组中小鼠的脾指数统计图;
图4为实施例中不同实验组中小鼠的胸腺指数统计图;
图5为实施例中不同实验组中小鼠的肺组织H&E染色病理切片(×200)图;
图6为实施例中不同实验组中小鼠肺组织中的病毒载量统计图;
图7为实施例中不同实验组中小鼠炎症因子的基因表达水平统计图;
图8为实施例中不同实验组中小鼠炎症因子的蛋白表达水平统计图。
具体实施方式
下面结合具体实施方式对本发明进行进一步的详细描述,给出的实施例仅为了阐明本发明,而不是为了限制本发明的范围。以下提供的实施例可作为本技术领域普通技术人员进行进一步改进的指南,并不以任何方式构成对本发明的限制。
下述实施例中的实验方法,如无特殊说明,均为常规方法,按照本领域内的文献所描述的技术或条件或者按照产品说明书进行。下述实施例中所用的材料、试剂等,如无特殊说明,均可从商业途径得到。
实施例
1、槐耳或其提取物的制备方法,包括如下操作:
乙醇溶液提取槐耳得到抽滤液,减压浓缩所述抽滤液得到浸膏,将所述浸膏进行硅胶色谱层析,依次用石油醚、二氯甲烷、乙酸乙酯、50%甲醇洗脱,得到甲醇洗脱液,减压浓缩所述甲醇洗脱液至浸膏剂,干燥所述浸膏剂至恒重,得到槐耳甲醇提取物;和/或乙醇溶液回流提取槐耳并去除槐耳的色素,分离药渣后纯水浓缩提取得到浓缩提取液,用乙醇沉淀所述浓缩提取液,然后除蛋白得到槐耳多糖提取物。
具体为:
制备槐耳甲醇提取物:将槐耳粉碎,以10倍量的70%乙醇溶液超声提取35分钟,提取3次,每次抽滤均分离出药渣,合并第一次抽滤液、第二次抽滤液和第三次抽滤液,得到所述抽滤液;将抽滤液减压浓缩后水浴至浸膏,并对浸膏进行真空干燥箱干燥至恒重;然后进一步进行硅胶色谱层析,选用长50cm,直径4cm色谱柱,柱内填充物质为硅胶,浸膏和硅胶比例1:5装柱,干法上样,依次用石油醚、二氯甲烷、乙酸乙酯、50%甲醇洗脱,每个梯度的流动相用量至少为3个柱体积,得到甲醇洗脱液,减压浓缩所述甲醇洗脱液至浸膏剂,真空干燥所述浸膏剂至恒重,得到槐耳甲醇提取物。
所述硅胶来自青岛海洋化工有限公司,硅胶的产品指标如下:
型号:规格3;
粒度:80-100目;
加热减量≤2%;
氯化物(CL)≤0.02%;
铁(Fe)≤0.02%;
pH(10%水悬浮液)6.0-7.0。
制备槐耳多糖提取物:另取槐耳实体粉末,以15倍量95%乙醇回流提取2小时除去色素,分离药渣以15倍量纯水煎煮提取三次,每次2小时,得到浓缩提取液,将所述浓缩提取液以4倍量的乙醇沉淀过夜,经sevage试剂除蛋白操作后即得槐耳多糖提取物。
2、H1N1病毒感染实验
为验证槐耳甲醇提取物和槐耳多糖提取物的抗H1N1病毒效果,本发明的发明人做了相关动物实验。在动物实验中,选取了72只小鼠随机分为9组,每组8只,分别为正常组(N)、模型组(M)、达菲组(D)、甲醇低剂量组(ML)、甲醇中剂量组(MM)、甲醇高剂量组(MH)、多糖低剂量组(PL)、多糖中剂量组(PM)、多糖高剂量组(PH)。
在适应性喂养小鼠的第三天,除正常组滴鼻20μL的生理盐水外,其他组每只小鼠等量滴鼻感染1个TCID50(1×105/100μL)的H1N1-PR8病毒,每日测定不同组小鼠的体重,待小鼠体重下降之日起甲醇低中高剂量组分别给槐耳甲醇提取物,量分别为4.68mg·kg-1·d1、7.00mg·kg-1·d1、14.00mg·kg-1·d1;多糖低中高剂量组分别给槐耳多糖提取物,量分别为17.85mg·kg-1·d1、27.00mg·kg-1·d1、53.50mg·kg-1·d1;达菲组给达菲(磷酸奥司他韦)剂量为19.5mg·kg-1·d1,正常组给与生理盐水,所有组连续给药7天,第八天解剖取肺、脾、胸腺、全血备用。
3、组织学观察
另外,本发明的发明人在实验中还作了肺组织学分析,如上所述感染小鼠在处死后,肺部用4%的多聚甲醛固定,石蜡包埋后,将小鼠肺切成2μm切片,然后对切片进行苏木精和伊红染色。
在病毒载量与细胞因子测定中,使用RNAprepPureTissueKit(Tiangen)提取肺组织中的总RNA。第一链cDNA合成使用FastKingRTKIT(withDNase;Tiangen)。实时PCR分析使用SuperRealPreMixPlus(Tiangen)和CFGConnect实时PCR系统(BIORAD)检测信号。检测肺组织中H1N1M基因、炎症因子IL-6、TNF-α、IFN-γ的表达量。引物序列如下:
H1N1Msense5‘-CTTCTAACCGAGGTCGAAAC-3’andantisense5‘-CGTCTACGCTGCAGTCCTC-3’;
IL-6sense5‘-GCTACCAAACTGGATATAATCAGGA-3’andantisense5‘-CCAGGTAGCTATGGTACTCCAGAA-3’;
TNF-αsense5‘-CTGTAGCCCACGTCGTAGC-3’andantisense5‘-TTGAGATCCATGCCGTTG-3’;
IFN-γsense5‘-CTTGAAAGACAATCAGGCCATC-3’andantisense5‘-CTTGGCAATACTCATGAATGCA-3’。
在肺组织匀浆中的IL-6、TNF-α、IFN-γ水平测定中,使用ELISA试剂盒(酶联免疫吸附测定试剂盒)进行测量,该试剂盒购自上海酶联生物科技有限公司。试剂盒中提供的稀释缓冲液用于稀释标准品和组织匀浆样本。接下来,将50μL样品或标准品添加到预先涂有抗体的微量滴定板的微孔中;将平板在37℃下孵育2小时;接着向每个孔中添加100μL生物素抗体,并在37℃下孵育1小时。接下来,加入100μL辣根过氧化酶(HorseradishPeroxidase,HRP)在37℃下孵育1小时,洗涤5次,添加底物并培养在37℃的黑暗中保持30分钟,最后加入50μL终止液终止反应,立即在450nm处使用酶标仪(Thermo)测定每孔的吸光度,确定系数标准曲线大于0.99。
4、实验结果
结果显示,相对于正常组小鼠而言,模型组中的小鼠(受到H1N1病毒感染的小鼠)肺组织中的肺指数均有所升高(参见图1),且体重呈下降趋势(参见图2),可代表已经成功造模。另外,模型组中的小鼠的肺指数显著升高,且均具有显著性差异(**P<0.01)。
达菲组、甲醇低剂量组、甲醇中剂量组、甲醇高剂量组、多糖低剂量组、多糖中剂量组和多糖高剂量组的小鼠体重较模型组有不同程度的升高,且比正常组体重低,肺指数相较于正常组有所升高,相较于模型组又均有不同程度的下降,且均具有显著性差异(**P<0.01,*P<0.05),脾指数各组差异并不明显(参见图3),胸腺指数模型组较正常组显著降低(参见图4)。
在模型组中,观察到肺泡腔气隙减少、肺泡间隔出现增宽和毛细血管扩张及淤血的重症肺炎症状(参见图5中的模型组图)。相比之下,在经槐耳提取物治疗的小鼠中(甲醇低剂量组、甲醇中剂量组、甲醇高剂量组、多糖低剂量组、多糖中剂量组、多糖高剂量组中的小鼠),肺泡腔较模型组均有着不同程度的增宽,细胞浸润情况明显改善,肺泡细胞壁厚度减少,肺部炎症的程度显著降低(参见图5)。
小鼠感染H1N1病毒后,达菲组及甲醇低剂量组、多糖低、中、高剂量组的肺病毒载量相较于模型组均有显著降低(**P<0.01,*P<0.05)(参见图6)。
通过测定小鼠肺组织中炎症因子IL-6、IFN-γ、TNF-α的基因表达水平(参见图7),结果可知模型组较正常组中三种炎症因子的水平均显著升高(**P<0.01),可进一步说明造模的成功。其中甲醇高剂量组与达菲组在IL-6的表达水平上较模型组有显著降低(*P<0.05),甲醇中剂量组与达菲组在IFN-γ的表达水平上较模型组有显著降低(*P<0.05),甲醇中剂量组在TNF-α的表达水平上较模型组有显著降低(*P<0.05),这表明甲醇的中高剂量组在对机体的炎症水平有一定的调节作用。
在通过ELISA试剂盒测定小鼠肺组织中炎症因子IL-6、IFN-γ、TNF-α的蛋白表达水平(参见图8)实验结果中,甲醇中剂量组、多糖中剂量组、达菲组在IL-6的表达水平上较模型组有显著降低(*P<0.05),甲醇中、高剂量组、多糖中、高剂量组与达菲组在IFN-γ的表达水平上较模型组有显著降低(*P<0.05),甲醇中剂量组、多糖中、高剂量组在TNF-α的表达水平上较模型组有显著降低(*P<0.05),这表明甲醇中、高剂量组与多糖中高剂量组在对机体的炎症水平有一定的调节作用。
以上对本发明进行了详述。对于本领域技术人员来说,在不脱离本发明的宗旨和范围,以及无需进行不必要的实验情况下,可在等同参数、浓度和条件下,在较宽范围内实施本发明。虽然本发明给出了特殊的实施例,应该理解为,可以对本发明作进一步的改进。总之,按本发明的原理,本申请欲包括任何变更、用途或对本发明的改进,包括脱离了本申请中已公开范围,而用本领域已知的常规技术进行的改变。按以下附带的权利要求的范围,可以进行一些基本特征的应用。
Claims (10)
1.槐耳或其提取物的应用,所述应用为以下(a1)和/或(a2)和/或(a3)和/或(a4)和/或(a5):
(a1)槐耳或其提取物在制备治疗流感病毒所致疾病的药物中的应用;
(a2)槐耳或其提取物在制备治疗流感病毒感染的药物中的应用;
(a3)槐耳或其提取物在制备预防流感病毒所致疾病的药物中的应用;
(a4)槐耳或其提取物在制备预防流感病毒感染的药物中的应用;
(a5)槐耳或其提取物在制备流感病毒抑制剂中的应用。
2.如权利要求1所述的应用,其特征在于,所述槐耳提取物为槐耳水提取物和/或槐耳醇提取物。
3.一种药物,其活性成分包括槐耳或其提取物;
所述药物的功能为以下(b1)和/或(b2)和/或(b3)和/或(b4):
(b1)治疗流感病毒所致疾病;
(b2)治疗流感病毒感染;
(b3)预防流感病毒所致疾病;
(b4)预防流感病毒感染。
4.如权利要求3所述的药物,其特征在于,所述槐耳提取物为槐耳水提取物和/或槐耳醇提取物。
5.槐耳提取物的制备方法,包括如下操作:
(一)乙醇溶液提取槐耳得到抽滤液,减压浓缩所述抽滤液得到浸膏,将所述浸膏进行硅胶色谱层析,依次用石油醚、二氯甲烷、乙酸乙酯、50%甲醇洗脱,得到甲醇洗脱液,减压浓缩所述甲醇洗脱液至浸膏剂,干燥所述浸膏剂至恒重,得到槐耳甲醇提取物;和/或
(二)乙醇溶液回流提取槐耳并去除槐耳的色素,分离药渣后纯水浓缩提取得到浓缩提取液,用乙醇沉淀所述浓缩提取液,然后除蛋白得到槐耳多糖提取物。
6.根据权利要求5所述的槐耳提取物的制备方法,其特征在于,所述操作(一)中乙醇溶液提取槐耳得到抽滤液的操作具体包括:
以10倍量的70%乙醇溶液超声提取槐耳粉末35分钟,提取次数为3次,每次抽滤均分离出药渣,合并第一次抽滤液、第二次抽滤液和第三次抽滤液,得到所述抽滤液。
7.根据权利要求5所述的槐耳提取物的制备方法,其特征在于,所述操作(一)中干燥所述浸膏剂至恒重的操作具体包括:真空干燥所述浸膏剂,得到所述槐耳甲醇提取物。
8.根据权利要求5所述的槐耳提取物的制备方法,其特征在于,所述操作(二)中分离药渣后纯水浓缩提取得到浓缩提取液的操作具体包括:分离药渣后以15倍量纯水煎煮提取三次,每次2小时,得到所述浓缩提取液。
9.权利要求5-8中任一项所述的制备方法制备得到的槐耳甲醇提取物或槐耳多糖提取物。
10.槐耳在制备权利要求9所述槐耳提取物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211374301.1A CN115531427B (zh) | 2022-11-04 | 2022-11-04 | 槐耳提取物在制备抗流感病毒药物中的应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202211374301.1A CN115531427B (zh) | 2022-11-04 | 2022-11-04 | 槐耳提取物在制备抗流感病毒药物中的应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN115531427A true CN115531427A (zh) | 2022-12-30 |
CN115531427B CN115531427B (zh) | 2023-11-24 |
Family
ID=84720146
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202211374301.1A Active CN115531427B (zh) | 2022-11-04 | 2022-11-04 | 槐耳提取物在制备抗流感病毒药物中的应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN115531427B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114574521A (zh) * | 2022-03-03 | 2022-06-03 | 山东中医药大学 | 一种基于平衡补偿的重组流感病毒构建方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106974943A (zh) * | 2017-01-22 | 2017-07-25 | 浙江中医药大学 | 一种槐耳醇提物的用途及制备方法 |
-
2022
- 2022-11-04 CN CN202211374301.1A patent/CN115531427B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106974943A (zh) * | 2017-01-22 | 2017-07-25 | 浙江中医药大学 | 一种槐耳醇提物的用途及制备方法 |
Non-Patent Citations (3)
Title |
---|
刘苗苗 等: "槐耳多糖提取及抗氧化性质的研究", 中国食用菌, vol. 32, no. 3, pages 47 * |
无: "冬春季流感遭遇疫情!增强自身免疫力,中医有妙招", pages 1, Retrieved from the Internet <URL:https://m.iplusmed.com/information/detail/3388.html> * |
陈霞飞 等: "中药槐耳抗肿瘤的相关研究进展", 黑龙江医学, vol. 42, no. 1, pages 90 - 92 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114574521A (zh) * | 2022-03-03 | 2022-06-03 | 山东中医药大学 | 一种基于平衡补偿的重组流感病毒构建方法 |
CN114574521B (zh) * | 2022-03-03 | 2023-09-12 | 山东中医药大学 | 一种基于平衡补偿的重组流感病毒构建方法 |
Also Published As
Publication number | Publication date |
---|---|
CN115531427B (zh) | 2023-11-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5512769B2 (ja) | 真菌免疫調節タンパク質の使用 | |
EP2246047B1 (en) | Use of lanostane derivatives in treating cachexia | |
CN107714805B (zh) | 衢枳壳提取物在制备中药制剂或功能性食品中的应用 | |
Zi-Kai et al. | Exploration of the mechanisms of Ge Gen Decoction against influenza A virus infection | |
CN115531427A (zh) | 槐耳或其提取物在制备抗流感病毒药物中的应用 | |
Fan et al. | Fermented ginseng attenuates lipopolysaccharide-induced inflammatory responses by activating the TLR4/MAPK signaling pathway and remediating gut barrier | |
EP3295950B1 (en) | Use of ginseng extract, ginsenoside and ginsenoside derivative in the preparation of medicine or health care product for treating cytomegalovirus infection disorders | |
WO2020093510A1 (zh) | 一种灵芝孢子多糖的分离纯化方法 | |
CN105148258A (zh) | 组合物及其应用,含有该组合物的制剂 | |
CN110075124A (zh) | AMSC-MALAT1-Exo用于制备治疗肝脏疾病的药物中的应用及其制备方法 | |
TW201000105A (en) | Pharmaceutical composition and extract of poria for treating a disease induced from immune disorder | |
CN112168833A (zh) | 知母皂苷酶解产物及其主要组分知母皂苷aⅲ的医药用途 | |
Lee et al. | KGC3P attenuates ovalbumin-induced airway inflammation through downregulation of p-PTEN in asthmatic mice | |
CN113577088B (zh) | 一种治疗病毒性肺炎的衢枳壳有效成分组及其制备方法与应用 | |
CN110179831A (zh) | 硫磺菌提取物的制药用途 | |
Yin et al. | Effect of traditional Chinese medicine Shu-Mai-Tang on attenuating TNFα-induced myocardial fibrosis in myocardial ischemia rats | |
CN111686107B (zh) | 化合物plx51107用于制备预防或治疗非洲猪瘟药物的新用途 | |
WO2014173058A1 (zh) | 一种槐耳多糖蛋白及其制备方法和用途 | |
CN113577158A (zh) | 一种治疗急性肺损伤的衢枳壳有效成分组及其制备方法与应用 | |
CN108752498B (zh) | 一种具有增强免疫活性的返魂草多糖及其制备方法与应用 | |
CN111346223A (zh) | 用于治疗乙型肝炎的药物制剂及其制备方法和用途 | |
CN116120389B (zh) | 人参皂苷Rg5及制备和在制备过敏性鼻炎药物中的应用 | |
CN115645442A (zh) | 槐耳或其提取物在制备抗新型冠状病毒药物中的应用 | |
CN106924329B (zh) | 一种艾迪制剂在制备治疗恶性滋养细胞肿瘤药物中的应用 | |
WO2014173056A1 (zh) | 槐耳多糖蛋白及其制备方法和用途 |
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 | ||
GR01 | Patent grant | ||
GR01 | Patent grant |