CN112168835B - 一种毛里求斯排草素在制备利胆药物中的应用 - Google Patents
一种毛里求斯排草素在制备利胆药物中的应用 Download PDFInfo
- Publication number
- CN112168835B CN112168835B CN202011206918.3A CN202011206918A CN112168835B CN 112168835 B CN112168835 B CN 112168835B CN 202011206918 A CN202011206918 A CN 202011206918A CN 112168835 B CN112168835 B CN 112168835B
- Authority
- CN
- China
- Prior art keywords
- mauritius
- expelin
- choleretic
- preparation
- inflammatory
- 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.)
- Active
Links
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- 229940079593 drug Drugs 0.000 title claims abstract description 10
- 239000008845 cholagoga Substances 0.000 title 1
- 229940124571 cholagogue Drugs 0.000 title 1
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 15
- 210000000941 bile Anatomy 0.000 claims abstract description 10
- 230000001989 choleretic effect Effects 0.000 claims abstract description 8
- 230000028327 secretion Effects 0.000 claims abstract description 7
- 230000003064 anti-oxidating effect Effects 0.000 claims abstract description 5
- 239000000731 choleretic agent Substances 0.000 claims abstract 8
- 239000003613 bile acid Substances 0.000 claims description 10
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 claims description 8
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910001424 calcium ion Inorganic materials 0.000 claims description 2
- 201000001352 cholecystitis Diseases 0.000 abstract description 8
- 201000001883 cholelithiasis Diseases 0.000 abstract description 8
- 208000001130 gallstones Diseases 0.000 abstract description 7
- 230000001965 increasing effect Effects 0.000 abstract description 6
- 230000031200 bile acid secretion Effects 0.000 abstract description 4
- 201000010099 disease Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 230000001737 promoting effect Effects 0.000 abstract description 2
- 235000013402 health food Nutrition 0.000 abstract 1
- 238000000338 in vitro Methods 0.000 abstract 1
- 238000001727 in vivo Methods 0.000 abstract 1
- 229930014626 natural product Natural products 0.000 abstract 1
- 229930003935 flavonoid Natural products 0.000 description 15
- 150000002215 flavonoids Chemical class 0.000 description 15
- 235000017173 flavonoids Nutrition 0.000 description 15
- 238000012360 testing method Methods 0.000 description 11
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 240000007332 Podocarpus macrophyllus Species 0.000 description 7
- 240000006322 Sambucus chinensis Species 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 230000003078 antioxidant effect Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 239000002031 ethanolic fraction Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 238000002835 absorbance Methods 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 238000002965 ELISA Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- HHEAADYXPMHMCT-UHFFFAOYSA-N dpph Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1[N]N(C=1C=CC=CC=1)C1=CC=CC=C1 HHEAADYXPMHMCT-UHFFFAOYSA-N 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000007760 free radical scavenging Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 206010061695 Biliary tract infection Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 208000003167 cholangitis Diseases 0.000 description 2
- 239000012916 chromogenic reagent Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 210000000232 gallbladder Anatomy 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000012089 stop solution Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 239000008812 xiaoyanlidan Substances 0.000 description 2
- 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 1
- KKADPXVIOXHVKN-UHFFFAOYSA-N 4-hydroxyphenylpyruvic acid Chemical compound OC(=O)C(=O)CC1=CC=C(O)C=C1 KKADPXVIOXHVKN-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- VYLJAYXZTOTZRR-BTPDVQIOSA-N CC(C)(O)[C@H]1CC[C@@]2(C)[C@H]1CC[C@]1(C)[C@@H]2CC[C@@H]2[C@@]3(C)CCCC(C)(C)[C@@H]3[C@@H](O)[C@H](O)[C@@]12C Chemical compound CC(C)(O)[C@H]1CC[C@@]2(C)[C@H]1CC[C@]1(C)[C@@H]2CC[C@@H]2[C@@]3(C)CCCC(C)(C)[C@@H]3[C@@H](O)[C@H](O)[C@@]12C VYLJAYXZTOTZRR-BTPDVQIOSA-N 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 206010008635 Cholestasis Diseases 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102100023195 Nephrin Human genes 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003591 anti-choleraic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- QXDMQSPYEZFLGF-UHFFFAOYSA-L calcium oxalate Chemical compound [Ca+2].[O-]C(=O)C([O-])=O QXDMQSPYEZFLGF-UHFFFAOYSA-L 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000007870 cholestasis Effects 0.000 description 1
- 231100000359 cholestasis Toxicity 0.000 description 1
- 210000001953 common bile duct Anatomy 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000000287 crude extract Substances 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000006049 herbal material Substances 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- VYLJAYXZTOTZRR-UHFFFAOYSA-N hopane-6alpha,7beta,22-triol Natural products C12CCC3C4(C)CCCC(C)(C)C4C(O)C(O)C3(C)C1(C)CCC1C2(C)CCC1C(C)(O)C VYLJAYXZTOTZRR-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 108010027531 nephrin Proteins 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- -1 potassium ferricyanide Chemical compound 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- 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
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- 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
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biochemistry (AREA)
- Alternative & Traditional Medicine (AREA)
- Molecular Biology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pain & Pain Management (AREA)
- Toxicology (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Botany (AREA)
- Medical Informatics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明公开了毛里求斯排草素用于制备利胆药物的用途，具有抗氧化、抗炎、提高总胆汁分泌量的用途，可用于制备治疗胆囊炎、胆结石等疾病，属于药用天然产物领域或保健食品制造业。申请人发现毛里求斯排草素具有体内体外抗炎及促胆汁酸分泌的作用，同时本发明公开了毛里求斯排草素用于制备利胆、治疗胆囊炎、胆结石药物的用途，在医药领域应用广阔。
Description
技术领域
本发明涉及医药领域，毛里求斯排草素具有抗氧化、抗炎、提高总胆汁酸分泌量的用途。
背景技术
金钱草药材为过路黄Lysimach christinae Hance的干燥全草，为川渝道地药材，其具有清热解毒、利尿排石、活血散淤的作用。金钱草中化学成分多样，其中黄酮为其主要活性成分。众所周知，药用植物里的黄酮类化合物是一类很好的天然抗氧化剂，能降低氧化应激反应和相关疾病的发病率。同时，其能通过调节促炎分子如肿瘤坏死因子(TNF-α)及炎症过程中产生的一氧化氮(NO)的产生抑制炎症过程，减少细胞凋亡及组织损伤。在日常生活中，自由基和活性氧作为人体副产物在细胞代谢过程中不断产生，如果不及时消除，容易导致功能性大分子的氧化损伤，引起很多跟衰老有关的的疾病。并且，炎症过程中产生的NO易与自由基如超氧化物结合产生高破坏性的过氧硝酸盐。黄酮类化合物在抗氧化及抗炎作用中起着极其重要的作用。研究表明，金钱草黄酮类化合物具有抗氧化、抗炎利胆及预防草酸钙结石形成和复发的作用。金钱草对肝胆结石的疗效尤为显著，而该病通常伴有胆道感染及胆汁淤积。研究表明，金钱草利胆排石作用主要是通过降低胆汁中游离胆红素和钙离子的含量，提高总胆汁酸的含量，从而抑制胆红素结石的形成。同时，其能增加胆汁分泌量，松弛胆囊平滑肌从而增加胆囊排空，并能有效抗炎，减少胆道感染。
金钱草黄酮类化合物的抗氧化及抗炎作用对于治疗肝胆结石类病症有明显的辅助作用。但金钱草总黄酮所含的毛里求斯排草素具有抗氧化、抗炎、提高总胆汁酸分泌量的作用或用于制备治疗胆囊炎、胆结石的药物均未见有关报道，具体的毛里求斯排草素的功效也未见有深入研究。
发明内容
申请人在对金钱草药理活性研究过程中，发现金钱草中总黄酮具有抗炎、提高总胆汁酸分泌量效果显著。从中发现及毛里求斯排草素为金钱草总黄酮发挥利胆作用的主要有效成分，申请人将毛里求斯排草素用于制备治疗胆囊炎、胆结石药物的用途。
申请人的进一步实验研究发现将毛里求斯排草素应用于治疗胆囊炎、胆结石疾病具有显著的效果，因此本申请还公开了将毛里求斯排草素用于制备治疗胆囊炎、胆结石疾病药物的用途.
本发明所述用途的药物，可以是毛里求斯排草素与药学上可接受的辅料采用常规的制剂工艺制成特定剂型，剂型不受到限制，只要是毛里求斯排草素可以制成的剂型即可，包括但不限于片剂、胶囊、颗粒剂。本发明所述用途的药物，制剂方法不受到限制，可以是制药领域任何一种可采用的制剂工艺。
本发明所述用途的药物，可以依据其自身特点主要采用口服给药的方法，其制剂剂型可以是片剂、颗粒剂、胶囊剂、软胶囊剂、口服液、混悬液等。
发明人进行的药理实验显示，毛里求斯排草素具有显著的具有抗氧化、抗炎、提高总胆汁酸分泌量的作用。因此本发明所述用途的药物临床上应用于治疗和/或预防治疗胆囊炎、胆结石。
附图说明
图1RAW 246.7细胞形态；a)对照组，b)LPS组，c)毛里求斯排草素20μg/mL，d)金钱草总黄酮100μg/mL，e)金钱草总黄酮200μg/mL，f)金钱草总黄酮300μg/mL(×200)
具体实施方式
下述实施例用于说明本发明的实现方式，并不仅限于用下述方法实施。
下述实施例中毛里求斯排草素可以采用常规的提取分离方法从金钱草获得，也可以购买毛里求斯排草素化学试剂。本发明所用的毛里求斯排草素利用金钱草提取分离获得，经检测其纯度为98.3％。
实施例1毛里求斯排草素的制备方法
样品溶液制备：称取金钱草药材粗粉2000g，用8倍量的70％乙醇回流提取，提取3次，每次2h，合并提取液，将提取液减压浓缩至无醇味，取出10mL作为总提取部位，其余部分4℃保存备用。
称取处理好的AB-8大孔树脂1000g，湿法装柱，将加纯水稀释并过滤好的金钱草粗提液(生药浓度5mg/mL)上柱，调节流速为1d/s。吸附完全后，用3BV纯水洗脱，控制流速为6BV/h，再分别用5BV 30％(或50％或70％或90％)乙醇洗脱，控制流速为3BV/h，收集乙醇洗脱液，减压浓缩、干燥，得金钱草30％乙醇部位(I)、50％乙醇部位(II)、70％乙醇部位(III)、90％乙醇部位(IV)，将70％乙醇部位(III)利用硅胶柱色谱分离得到毛里求斯排草素。
实施例2毛里求斯排草素的活性考察1
DPPH自由基清除试验：DPPH自由基清除实验。取200μL毛里求斯排草素，加入800μLDPPH甲醇溶液，充分混合后于室温放置60min，在517nm处测定吸光度。以纯水作为空白对照。
还原性实验：取2mL一系列浓度的毛里求斯排草素，用甲醇稀释成溶液后加入2.5mL1％的铁氰化钾溶液，于50℃水浴中反应20min，然后加入2.5mL 10％的三氯乙酸，混合液于3000rpm下离心10min，取2.5mL上清液，向其中加入2.5mL纯水与0.5mL 0.1％的FeCl3溶液，于700nm处测定吸光度。以纯水为空白对照。
NO/亚硝酸盐的测定：NO的释放量通过亚硝酸盐的含量间接反映，细胞用金钱草总黄酮(300μg/mL)以及毛里求斯排草素(50μg/mL)预先孵育1h，然后加入终浓度为1mg/mL的LPS，继续置5％CO2培养箱中于37℃孵育24h。取100μL培养基与相同体积的Griess试剂混合，于室温孵育10min，采用酶标仪于540nm处测定吸光度。
人总胆汁酸(TBA)酶联免疫分析试验：人总胆汁酸(TBA)酶联免疫分析试剂盒制备标准品，分别设空白孔(空白对照孔不加样品及酶标试剂)、标准孔、待测样品孔。在酶标包被板上标准品准确加样50μL，待测样品孔中先加样品稀释液40μL，然后再加待测样品10μL(25μg/mL)。加样将样品加于酶标板孔底部，轻轻摇晃混匀。用封板膜封板后置37℃温育30分钟。将30倍浓缩洗涤液用蒸馏水30倍稀释后备用，小心揭掉封板膜，弃去液体，甩干，每孔加满洗涤液，静置30秒后弃去，如此重复5次，拍干。每孔加入酶标试剂50μL，空白孔除外。温育、洗涤，每孔先加入显色剂A50μL，再加入显色剂B50μL，轻轻震荡混匀，37℃避光显色10分钟。每孔加终止液50μL，终止反应。以空白孔调零，450nm波长依序测量各孔的吸光度(CD值)。测定应在加终止液后15分钟以内进行。
实验结果：对金钱草总黄酮和毛里求斯排草素分别进行DPPH自由基清除试验、还原性试验及细胞抗炎实验，并计算其IC50值，结果如表1所示。结果表明毛里求斯排草素抗氧化及细胞抗炎能力最强。
表1金钱草总黄酮与毛里求斯排草素抗氧化及抗炎结果
对试验中的小鼠RAW246.7巨噬细胞进行观察(图1)，从倒置显微镜中可以看出，与正常对照组相比，LPS刺激后变形的细胞明显增加，巨噬细胞原本扁平的外形因LPS的刺激使细胞质凸出并向四周蔓延，细胞形态学的改变表明LPS刺激导致的炎症模型成功。然而，金钱草极性总黄酮和毛里求斯排草素对LPS具有拮抗作用，使细胞变形程度减少。
在人总胆汁酸(TBA)酶联免疫分析试验中，空白孔板的胆汁酸浓度为1.59mmol/mL，毛里求斯排草素组胆汁酸浓度为2.09mmol/mL。说明了具有促胆汁酸分泌的作用。
实施例3毛里求斯排草素的活性考察2
雌雄各半的SD大鼠总计50只，适应性喂养一周后，随机分为5组，每组10只。空白对照组灌服蒸馏水，阳性药物对照组灌服中成药消炎利胆片混悬液，实验组灌服毛里求斯排草素混悬液高、中、低3种剂量。每日灌胃一次，持续7天。于第7天，灌胃给药1小时后，进行麻醉并行胆总管引流，分别记录第一、二、三小时总共三个时段的胆汁流量，对不同时段的三组胆汁流量变化进行观察对比。
实验结果：通过对各组胆汁流量的计量观察，对照组和实验组的胆汁流量均比空白组增加，毛里求斯排草素高、种、低3个剂量组与消炎利胆片阳性药物对照组均能增高胆汁分泌量，其中毛里求斯排草素高剂量组增加最显著，且表现了一定的剂量依赖性。
三、结论
本发明通过对毛里求斯排草素的抗氧化试验、抗炎试验、促进胆汁酸分泌实验，结果表明毛里求斯排草素具有较好的抗氧化试验、抗炎试验、促进胆汁酸分泌的效果，对于治疗胆囊炎、胆结石等疾病提供依据。
Claims (4)
1.毛里求斯排草素在制备利胆药物中的用途。
2.根据权利要求1所述的毛里求斯排草素在制备利胆药物中的用途，所述利胆作用是通过抗氧化、抗炎、提高总胆汁酸分泌量来发挥的。
3.根据权利要求1的毛里求斯排草素在制备利胆药物用途，所述利胆是降低胆汁中游离胆红素。
4.根据权利要求1的毛里求斯排草素在制备利胆药物用途，所述利胆是降低胆汁中钙离子含量。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011206918.3A CN112168835B (zh) | 2020-11-03 | 2020-11-03 | 一种毛里求斯排草素在制备利胆药物中的应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011206918.3A CN112168835B (zh) | 2020-11-03 | 2020-11-03 | 一种毛里求斯排草素在制备利胆药物中的应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112168835A CN112168835A (zh) | 2021-01-05 |
| CN112168835B true CN112168835B (zh) | 2022-04-08 |
Family
ID=73917172
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202011206918.3A Active CN112168835B (zh) | 2020-11-03 | 2020-11-03 | 一种毛里求斯排草素在制备利胆药物中的应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112168835B (zh) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101759678A (zh) * | 2009-11-20 | 2010-06-30 | 南京泽朗医药科技有限公司 | 一种山奈酚的制备方法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1931228B (zh) * | 2006-09-25 | 2011-11-16 | 沈阳药科大学 | 金钱草总黄酮提取物及其制备方法 |
-
2020
- 2020-11-03 CN CN202011206918.3A patent/CN112168835B/zh active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101759678A (zh) * | 2009-11-20 | 2010-06-30 | 南京泽朗医药科技有限公司 | 一种山奈酚的制备方法 |
Non-Patent Citations (2)
| Title |
|---|
| 广西茉莉花叶黄酮类化合物抗氧化活性及其构效关系和作用机理研究;李月仕;《中国优秀博硕士学位论文全文数据库（硕士） 医药卫生科技辑》;20170515(第5期);第E057-53页，尤其是第67页第1-2段 * |
| 李月仕.广西茉莉花叶黄酮类化合物抗氧化活性及其构效关系和作用机理研究.《中国优秀博硕士学位论文全文数据库（硕士） 医药卫生科技辑》.2017,(第5期), * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112168835A (zh) | 2021-01-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Van et al. | Anti-inflammatory effect of Inonotus obliquus, Polygala senega L., and Viburnum trilobum in a cell screening assay | |
| US9241964B2 (en) | Composition from Sphaeranthus indicus and Garcinia mangostana for the control of metabolic syndrome | |
| CN110893197B (zh) | 用于治疗痛风的蔓三七提取物及其制备方法 | |
| Peng et al. | Bioactive compounds and bioactive properties of Chaga (Inonotus obliquus) mushroom: A review | |
| CN106474145A (zh) | 辣木叶多糖在制备防治酒精性肝损伤药物和食品中的应用 | |
| Mujawdiya et al. | Mangiferin: A potential natural molecule for management of metabolic syndrome | |
| CN105601707B (zh) | 一种蒲公英籽抗氧化四肽及其制备方法 | |
| WO2025021222A1 (zh) | 菊苣乙酸乙酯萃取物在胃黏膜损伤类疾病预防和治疗药物中的应用 | |
| CN112168835B (zh) | 一种毛里求斯排草素在制备利胆药物中的应用 | |
| Liao et al. | Hylocereus undatus flower suppresses DSS-induced colitis in mice by reducing intestinal inflammation, repairing the intestinal physical barrier, and modulating gut and lung microbiota | |
| Ga et al. | Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation | |
| CN102151306B (zh) | 一种从荔枝果肉中提取的活性组合物及其制备方法和应用 | |
| CN107088206A (zh) | 一种桑白皮提取物的制备方法及其应用 | |
| CN103800466B (zh) | 一种治疗口腔及消化道炎症或/和溃疡的马甲子提取物及制剂和应用 | |
| CN112057535B (zh) | 一种预防或/和治疗血脂异常的中药组合物的制备方法 | |
| KR20240048167A (ko) | 울금을 이용한 낙산균 발효물을 포함하는 염증성 장질환 개선용 건강기능식품 | |
| CN105687217B (zh) | 一种苯丙素类化合物及其药学上可接受的盐在制备治疗炎症性疾病的药物中的应用 | |
| CN117100801A (zh) | 一种抗特异性皮炎的药物组合物及其制备方法和用途 | |
| TW202126320A (zh) | 一種具治療或改善胃潰瘍功效的魚針草生物活性分餾物tsyi-813與其組合物、製備方法及用途 | |
| CN113116976A (zh) | 一种中药组合物在制备预防或治疗消化内科疾病药物中的应用 | |
| Usmani et al. | Therapeutic potential of metalloherbal nanoceuticals: current status and future perspectives | |
| CN101502571B (zh) | 一种活血、镇痛和抗炎的药物和应用 | |
| KR100779026B1 (ko) | 염증성 질환 치료 및 예방에 유용한 구골 추출물 | |
| KR20070088940A (ko) | 우슬 추출물을 함유하는 염증성 질환의 치료 및 예방에유용한 약제 | |
| CN111166796B (zh) | 一种治疗皮肤炎症的复方制剂及其制备方法 |
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 |