CN114702467B - Aromatic cassane diterpenoid compound of golden pineapple, extraction method and application - Google Patents
Aromatic cassane diterpenoid compound of golden pineapple, extraction method and application Download PDFInfo
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- CN114702467B CN114702467B CN202210514845.7A CN202210514845A CN114702467B CN 114702467 B CN114702467 B CN 114702467B CN 202210514845 A CN202210514845 A CN 202210514845A CN 114702467 B CN114702467 B CN 114702467B
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- -1 Aromatic cassane diterpenoid compound Chemical class 0.000 title claims abstract description 22
- 229930002147 cassane Natural products 0.000 title claims abstract description 22
- 235000007119 Ananas comosus Nutrition 0.000 title claims abstract description 16
- 238000000605 extraction Methods 0.000 title claims abstract description 11
- 244000099147 Ananas comosus Species 0.000 title abstract 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 54
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 45
- 238000002360 preparation method Methods 0.000 claims abstract description 25
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 15
- 238000004440 column chromatography Methods 0.000 claims abstract description 13
- 239000000284 extract Substances 0.000 claims abstract description 11
- 241000193755 Bacillus cereus Species 0.000 claims abstract description 8
- 241000191967 Staphylococcus aureus Species 0.000 claims abstract description 8
- 239000002024 ethyl acetate extract Substances 0.000 claims abstract description 8
- 238000010992 reflux Methods 0.000 claims abstract description 7
- 244000298697 Actinidia deliciosa Species 0.000 claims abstract description 6
- 235000009436 Actinidia deliciosa Nutrition 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 150000001298 alcohols Chemical class 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 138
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 32
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 16
- 239000002904 solvent Substances 0.000 claims description 16
- 239000003208 petroleum Substances 0.000 claims description 15
- 238000010828 elution Methods 0.000 claims description 14
- 241000234671 Ananas Species 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- 239000000499 gel Substances 0.000 claims description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 10
- 238000000926 separation method Methods 0.000 claims description 10
- 239000000741 silica gel Substances 0.000 claims description 10
- 229910002027 silica gel Inorganic materials 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 238000009472 formulation Methods 0.000 claims description 9
- 238000010898 silica gel chromatography Methods 0.000 claims description 9
- 239000012071 phase Substances 0.000 claims description 8
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 6
- 239000003826 tablet Substances 0.000 claims description 6
- 241000233805 Phoenix Species 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000011161 development Methods 0.000 claims description 5
- 230000018109 developmental process Effects 0.000 claims description 5
- 239000007791 liquid phase Substances 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 239000000287 crude extract Substances 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 4
- 238000010298 pulverizing process Methods 0.000 claims description 4
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 claims description 3
- ROAYSRAUMPWBQX-UHFFFAOYSA-N ethanol;sulfuric acid Chemical compound CCO.OS(O)(=O)=O ROAYSRAUMPWBQX-UHFFFAOYSA-N 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 239000012669 liquid formulation Substances 0.000 claims description 3
- 230000011218 segmentation Effects 0.000 claims description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 claims description 2
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 229940125773 compound 10 Drugs 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000004599 antimicrobial Substances 0.000 claims 2
- 238000007796 conventional method Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 11
- 241000894006 Bacteria Species 0.000 abstract description 5
- 241000196324 Embryophyta Species 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 238000002474 experimental method Methods 0.000 abstract description 3
- 244000052616 bacterial pathogen Species 0.000 abstract description 2
- 244000144972 livestock Species 0.000 abstract description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 238000002114 high-resolution electrospray ionisation mass spectrometry Methods 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 229930004069 diterpene Natural products 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000013078 crystal Substances 0.000 description 4
- 150000004141 diterpene derivatives Chemical class 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000013049 sediment Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 2
- 241000522234 Caesalpinia Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 208000022362 bacterial infectious disease Diseases 0.000 description 2
- 230000003385 bacteriostatic effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000010413 mother solution Substances 0.000 description 2
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 2
- 238000007873 sieving Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- 241000186046 Actinomyces Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 235000007627 Caesalpinia Nutrition 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000220485 Fabaceae Species 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 241000589615 Pseudomonas syringae Species 0.000 description 1
- 241001052560 Thallis Species 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000078 anti-malarial effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 235000019568 aromas Nutrition 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- WBKFWQBXFREOFH-UHFFFAOYSA-N dichloromethane;ethyl acetate Chemical compound ClCCl.CCOC(C)=O WBKFWQBXFREOFH-UHFFFAOYSA-N 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 238000005325 percolation Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000017807 phytochemicals Nutrition 0.000 description 1
- 229930000223 plant secondary metabolite Natural products 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229930004725 sesquiterpene Natural products 0.000 description 1
- 150000004354 sesquiterpene derivatives Chemical class 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
-
- 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
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/10—Aromatic or araliphatic carboxylic acids, or thio analogues thereof; 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
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/36—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
-
- 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
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing within the same carbon skeleton a carboxylic group or a thio analogue, or a derivative thereof, and a carbon atom having only two bonds to hetero atoms with at the most one bond to halogen, e.g. keto-carboxylic acids
-
- 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
- A01N43/06—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 five-membered rings
- A01N43/08—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 five-membered rings with oxygen as the ring hetero atom
-
- 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
- A61P31/04—Antibacterial agents
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
- C07C69/78—Benzoic acid esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/22—Ortho- or ortho- and peri-condensed systems containing three rings containing only six-membered rings
- C07C2603/26—Phenanthrenes; Hydrogenated phenanthrenes
-
- 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
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Environmental Sciences (AREA)
- Plant Pathology (AREA)
- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- Pest Control & Pesticides (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Agronomy & Crop Science (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses an aromatic cassane diterpenoid compound of golden pineapple, an extraction method and application thereof, which comprises the steps of crushing stems of golden pineapple, and carrying out heat reflux extraction in alcohols to obtain total extract; extracting the total extract with ethyl acetate, and repeatedly subjecting the obtained ethyl acetate extract phase to column chromatography. The compound provided by the invention has a simple preparation method, and the prepared compound or pharmaceutically acceptable salt thereof can be used for preparing an antibacterial agent preparation, and experiments prove that the compound has good antibacterial activity on plant bacteria such as kiwifruit canker and bacillus cereus, has good antibacterial activity on pathogenic bacteria such as staphylococcus aureus, and is safe to environment, people, livestock and other beneficial organisms.
Description
Technical Field
The invention belongs to the field of natural pharmaceutical chemistry, and particularly relates to a golden pineapple aromatized cassane diterpenoid compound, an extraction method and application.
Background
The genus Caesalpinia plants (CAESALPINIA) of the family Leguminosae belong to about 100 species, are widely distributed in tropical and subtropical regions, 17 species in China, and are mainly distributed in southwest to south regions. According to literature reports, the plant belongs to the genus phytochemical is rich in components, mainly comprises diterpene, triterpene, sesquiterpene, alkaloid, saponin, glycoside and other compounds, wherein cassane diterpene is a characteristic component of the genus and has wide pharmacological activity, plays an important role in various aspects such as antibiosis, antimalarial, anti-inflammatory, antitumor and the like, but few reports on aromatization cassane diterpene are provided at present, no related report on the antibacterial activity of the diterpene is provided, and further research on functional active components of the diterpene is still needed to develop the medicinal value of the diterpene.
Disclosure of Invention
Aiming at the defects and the shortcomings of the prior art, the invention aims to provide a golden phoenix flower aromatized cassane diterpenoid compound, an extraction method and application.
In order to achieve the above purpose, the application is realized by adopting the following technical scheme: the application provides an aromas cassane diterpenoid compound of golden phoenix flower, which has any one or more of structures shown in formulas 1 to 12:
A method for extracting aromatic cassane diterpenoid compounds from herba Pteridis Multifidae comprises pulverizing stems of herba Pteridis Multifidae, and extracting under reflux in alcohol to obtain total extract; extracting the total extract with ethyl acetate, and repeatedly subjecting the obtained ethyl acetate extract phase to column chromatography.
Still further, the alcohols include methanol and ethanol.
Further, the extraction method specifically comprises the following steps:
Drying stems of the phoenix-tail fern in shade, pulverizing to 30 meshes, heating and refluxing in methanol to obtain an extracting solution, concentrating the extracting solution under reduced pressure to recover methanol to obtain a crude extract, and extracting the crude extract with ethyl acetate to obtain an ethyl acetate extract phase;
Dissolving an ethyl acetate extract phase by using chloroform or acetone, then carrying out column chromatography segmentation and rough separation by using silica gel, and carrying out gradient elution by using a chloroform/acetone system, wherein the volume ratio of the gradient elution of the chloroform/acetone system is sequentially 1:0, 9:1, 8:2, 7:3, 1:1 and 0:1; taking sulfuric acid ethanol solution as a color developing agent, and combining similar fractions according to TLC color development to obtain 8 components EA 1-EA 8;
After the EA2 component is subjected to silica gel column chromatography, carrying out gradient elution by using a petroleum ether/ethyl acetate system, wherein the elution concentrations of the petroleum ether/ethyl acetate system are sequentially 30:1, 25:1, 20:1 and 10:1 in volume ratio, and 8 components 2A-2H are obtained according to the polarity;
separating the component 2C by sequentially performing a forward silica gel chromatographic column, an RP-C 18 reverse chromatographic column and a Sephadx-LH20 gel chromatographic column to obtain compounds 4 and 5;
Separating out crystals in the component 2D, and repeatedly recrystallizing and purifying by methanol to obtain a compound 2;
Separating the component 2D washing solution sequentially by forward chromatographic column, sephadx-LH20 gel chromatographic column and RP-C 18 reverse chromatographic column to obtain compounds 3 and 9;
Separating the component 2E by RP-C 18 reverse chromatographic column, forward silica gel chromatographic column and Sephadx-LH20 gel chromatographic column to obtain compounds 1 and 10;
Carrying out forward silica gel column chromatography on the component EA3, carrying out coarse separation by using a petroleum ether-ethyl acetate system, and obtaining 9 components 69A-69G according to the polarity, wherein the volume ratio of the petroleum ether-ethyl acetate system is 7:1, 5:1, 3:1 and 1:1 in sequence;
After preparing a liquid phase from the component 69D through an RP-C 18 half, carrying out chromatography through an RP-C 18 chromatographic column and a Sephadx-LH20 chromatographic column to obtain a compound 8, wherein the solvent used for preparing the liquid phase through the RP-C 18 half is methanol with volume concentration of 20%, 40%, 60%, 80% and 100% in sequence;
The component 69F is sequentially subjected to a chloroform-methanol gel column, an RP-C 18 chromatographic column and a high performance liquid chromatography preparation column in a volume ratio of 1:1 to obtain compounds 11 and 12;
Subjecting the component 69G to RP-C 18 chromatographic column and Sephadx-LH20 gel column chromatography in sequence to obtain a compound 6;
After the component EA-4 is subjected to forward silica gel column chromatography and coarse separation, obtaining components 1a-1g according to the polarity; component 1a is eluted by adopting an MCI column gradient, and the volume concentration of methanol eluted by the MCI column gradient is 20%, 40%, 60%, 80% and 100% in sequence; purifying the 60% methanol section by Sephadx-LH20 column chromatography to obtain the compound 7.
The invention also discloses application of the aromatic cassane diterpenoid compound of the golden pineapple or pharmaceutically acceptable salt thereof in preparing an antibacterial agent preparation.
Furthermore, the antibacterial agent preparation is used for preventing and controlling kiwi fruit canker, bacillus cereus and staphylococcus aureus.
Furthermore, the antibacterial agent preparation is prepared into a pharmaceutically acceptable preparation by adding pharmaceutically acceptable auxiliary materials according to a conventional process, and the pharmaceutically acceptable preparation is a solid preparation or a liquid preparation.
Still further, the solid preparation comprises granules, capsules, tablets and pills; the liquid formulation includes an injectable formulation.
Furthermore, in the antibacterial agent preparation, the content of the aromatic cassane diterpenoid compounds or the pharmaceutically acceptable salts thereof of the golden pineapple is 2-8 percent by mass percent.
Compared with the prior art, the invention has the beneficial technical effects that:
The compound provided by the invention has a simple preparation method, and the prepared compound or pharmaceutically acceptable salt thereof can be used for preparing an antibacterial agent preparation, and experiments prove that the compound has good antibacterial activity on plant bacteria such as kiwifruit canker and bacillus cereus, has good antibacterial activity on pathogenic bacteria such as staphylococcus aureus, and is safe to environment, people, livestock and other beneficial organisms. The antibacterial agent formulation prepared by using the compound of the present invention may be administered orally, nasally, rectally or parenterally, and may be formulated into conventional solid formulations, liquid formulations or solutions for injection, etc., preferably tablets, capsules and injections.
Drawings
The accompanying drawings are included to provide a further understanding of the disclosure, and are incorporated in and constitute a part of this specification, illustrate the disclosure and together with the description serve to explain, but do not limit the disclosure. In the drawings:
FIG. 1 is a specific isolation scheme for compounds of the invention.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only 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 compounds of the present disclosure may be obtained by a variety of techniques, such as chemical synthesis; as another example, from other seeds of the genus Caesalpinia, the extraction process may be by any of a variety of known techniques, such as: supercritical fluid extraction, thermal reflux extraction with solvent (ethanol, methanol, acetone, etc.), percolation with solvent (ethanol, methanol, acetone, etc.), etc.
The golden phoenix flowers used in the present disclosure were collected in Xishuangbanna, yunnan, 5 months, and identified by doctor Wang Zehuan, kunming plant institute, academy of sciences of China.
In the invention, 8 components are obtained by combining similar fractions according to TLC color development, components 2A-2H are obtained by gradient elution through a petroleum ether/ethyl acetate system, components 69A-69G are obtained by rough separation through a petroleum ether/ethyl acetate system, each component is named according to the polarity-size outflow sequence, namely, the outflow is firstly performed with small polarity, the outflow is performed after the polarity is large, and the similar components are combined according to the TLC color development condition.
The biological activity measurement result and the physiological and biochemical experiment result in the embodiment of the invention prove that the aromatic cassane diterpenoid compounds of the golden pineapple have antibacterial activity. Those skilled in the art will appreciate that the biological activity assay results and physiological and biochemical experimental results establish the general utility of the aromatic cassane diterpenoids of the golden pineapple as antibacterial agents.
In order to better understand the essence of the invention, the technical contents of the invention will be described in detail with examples, but the invention is not limited to these examples.
Example 1:
The embodiment discloses an aromatised cassane diterpenoid compound of golden phoenix flower, which has any one of structures shown in formulas 1 to 12 or a combination thereof:
The physical and spectroscopic data for compounds 1-12 are as follows:
Compound 1: colorless needle crystals; CD(MeOH)λmax(Δε):191(+44.8),190(-36.6);UV(MeOH)λmax(logε)207(0.78)nm;IR(KBr)νmax 3494,2931,2384,2311,1724cm-1;HR-ESI-MS m/z 557.21478[M+Na]+[calcd for C31H34O8Na,557.21479];1H and 13C NMR The data are shown in Table-1.
Compound 2: colorless needle crystals; CD(MeOH)λmax(Δε):228(+57.9),251(-36.2);UV(MeOH)λmax(logε)215(3.87)nm;IR(KBr)νmax 3495,2929,2384,2311,1706cm-1;HR-ESI-MS m/z471.17795[M+Na]+(calcd for C27H28O6Na,471.17781);1H and 13C NMR The data are shown in Table-1.
Compound 3: white amorphous powder; CD(MeOH)λmax(Δε):191(+13.9),193(-7.9);UV(MeOH)λmax(logε)207(0.65)nm;IR(KBr)νmax 3735,3554,3535,3515,2931,2385,2312,1719cm-1;HR-ESI-MS m/z 499.20929[M+Na]+(calcd for C29H32O6Na,499.20911);1H and 13C NMR The data are shown in Table-2.
Compound 4: white amorphous powder; CD(MeOH)λmax(Δε):191(+12.5),221(-6.7);UV(MeOH)λmax(logε)218(4.39)nm;IR(KBr)νmax 3554,2927,2862,2386,2312,1709cm-1;HR-ESI-MS m/z 467.21942[M+Na]+(calcd for C29H32O4Na,467.21928);1H and 13C NMR The data are shown in Table-2.
Compound 5: white amorphous powder; CD(MeOH)λmax(Δε):278(+4.5),191(-19.2);UV(MeOH)λmax(logε)214(1.23)nm;IR(KBr)νmax3737,3598,3556,3514,3338,2927,2859,2383,2311,1705cm-1.HR-ESI-MS m/z441.20383[M+Na]+(calcd for C27H30O4Na,441.20363);1H and 13C NMR The data are shown in Table-3.
Compound 6: brown amorphous powder; CD(MeOH)λmax(Δε):190(+13.9),196(-3.6);UV(MeOH)λmax(logε)190(4.27)nm;IR(KBr)νmax3435,2928,2362,1708cm-1;HR-ESI-MS m/z 531.19801[M+Na]+(calcd for C29H32O8Na,531.19828);1H and 13C NMR The data are shown in Table-3.
Compound 7: white amorphous powder; CD(MeOH)λmax(Δε):191(+14.5),221(-36.7);UV(MeOH)λmax(logε)219(2.10)nm;IR(KBr)νmax3392,2940,2877,2326,1731cm-1;HR-ESI-MS m/z 565.20380[M+Na]+(calcd for C29H30O10Na,565.20497)1H and 13C NMR The data are shown in Table-4.
Compound 8: white amorphous powder; CD(MeOH)λmax(Δε):238(+42.3),205(-18.5);UV(MeOH)λmax(logε)202(2.53)nm;IR(KBr)νmax 3365,2928,2384,2311,1716cm-1;HR-ESI-MS m/z 657.26697[M+Na]+(calcd for C36H42O10Na,657.26702);1H and 13C NMR The data are shown in Table-4.
Compound 9: white amorphous powder; CD(MeOH)λmax(Δε):191(+2.11),236(-40.1);UV(MeOH)λmax(logε)201(1.77)nm;IR(KBr)νmax 3397,2929,2868,2600,2547,2388,2309,1713cm-1;HR-ESI-MS m/z 431.25583[M+Na]+(calcd for C27H36O3Na,431.25567);1H and 13C NMR The data are shown in Table-5.
Compound 10: white amorphous powder; CD(MeOH)λmax(Δε):190(+7.8),234(-19.5);UV(MeOH)λmax(logε)227(1.71)nm;IR(KBr)νmax3514,2922,2856,2571,2384,2312,1742cm-1;HR-ESI-MS m/z 463.24551[M+Na]+(calcd for C27H36O5Na,463.24550);1H and 13C NMR The data are shown in Table-5.
Compound 11: white amorphous powder; CD(MeOH)λmax(Δε):190(+20.0),193(-8.8);UV(MeOH)λmax(logε)201(1.63)nm;IR(KBr)νmax 3454,2928,2860,2383,2311,1715cm-1;HR-ESI-MS m/z 509.25119[M+Na]+(calcd for C28H38O7Na,509.25097);1H and 13C NMR The data are shown in Table-6.
Compound 12: colorless oily form; UV(MeOH)λmax(logε)230(0.71)nm;HR-ESI-MS m/z 429.22223[M+H]+(calcd for C25H33O6 429.22299);1H and 13C NMR The data are shown in Table-6.
Table-1 data for 1 H and 13 C-NMR of Compounds 1 and 2
1 H and 13 C-NMR data for Table-2 Compounds 3 and 4
1H,13 C-NMR data for Compounds 5 and 6 of Table-3
1H,13 C-NMR data for Compounds 7 and 8 of Table-4
1H,13 C-NMR data for Compounds 9 and 10 of Table-5
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1H,13 C-NMR data for Compounds 11 and 12 of Table-6
Note that: the nuclear magnetic data are all measured by a Bruker DRX-500MHz nuclear magnetic resonance instrument.
Example 2
As shown in fig. 1, the embodiment discloses an extraction method of aromatic cassane diterpenoid compounds of golden pineapple, which specifically comprises the following steps:
Drying stem of herba Pteridis Multifidae in shade, pulverizing to 30 mesh, extracting under reflux in methanol for three times to obtain extractive solution, concentrating under reduced pressure to recover methanol to obtain extract, concentrating under reduced pressure for five times repeatedly, and mixing the extracts to obtain total extract.
The total extract was dispersed in an appropriate amount of water, extracted five times with ethyl acetate and n-butanol respectively (v/v 1:1), and the extracts were combined and concentrated under reduced pressure to give ethyl acetate phase (400 g).
Dissolving an ethyl acetate extract phase by using chloroform or acetone, then carrying out column chromatography segmentation and rough separation by using silica gel, and carrying out gradient elution by using a chloroform/acetone system, wherein the solvent volume ratio of the gradient elution of the chloroform/acetone system is sequentially 1:0, 9:1, 8:2, 7:3, 1:1 and 0:1; taking sulfuric acid ethanol solution as a color developing agent, combining similar fractions according to TLC color development to obtain 8 components EA 1-EA 8, wherein the polarity sequence of EA 1-EA 8 is from small to large;
After the EA2 component is subjected to silica gel column chromatography, carrying out gradient elution by using a petroleum ether/ethyl acetate system, wherein the volume ratio of the petroleum ether/ethyl acetate system elution is sequentially 30:1, 25:1, 20:1 and 10:1, 8 components 2A-2H are obtained according to the polarity, and the polarity sequence of the components 2A-2H is from small to large;
Separating component 2C by forward silica gel chromatographic column, RP-C 18 reverse chromatographic column and Sephadx-LH20 gel chromatographic column (methanol) to obtain compounds 4 and 5; wherein the forward silica gel chromatographic column is eluted by adopting a methylene dichloride-ethyl acetate system, and the volume ratio of the solvents is 50:1, 40:1, 30:1, 10:1 and 0:1; the RP-C 18 reverse chromatographic column is eluted by a methanol-water system, and the volume ratio is 3:2, 2:1, 3:1 and 1:0;
separating out crystals in the component 2D, and repeatedly recrystallizing and purifying by methanol to obtain a compound 2;
Separating the washing liquid of the component 2D sequentially by forward chromatographic column, sephadx-LH20 (acetone) and RP-C 18 column chromatography to obtain compounds 3 and 9, wherein the volume ratio of the solvent of the n-hexane-ethyl acetate system adopted by the forward chromatographic column is 20:1, 15:1, 10:1 and 5:1, and the volume ratio of the solvent of the acetone-water system adopted by the RP-C 18 column is 1:1, 3:2 and 2:1;
Separating the component 2E by an RP-C 18 column, a forward silica gel chromatographic column and a Sephadx-LH20 gel column (acetone) respectively to obtain compounds 1 and 10, wherein the RP-C 18 column uses methanol-water as an eluting solvent, the volume ratio of the solvent is 2:1, 3:1 and 1:0, and the forward silica gel chromatographic column is eluted by a petroleum ether-ethyl acetate system, and the volume ratio is 15:1, 12:1, 8:1 and 5:1 in sequence;
Carrying out forward silica gel column chromatography on the component EA3, carrying out coarse separation by using a petroleum ether-ethyl acetate system, obtaining 7 components 69A-69G according to the polarity, wherein the polarity sequence of the components 69A-69G is from small to large, and the solvent volume ratio of the petroleum ether-ethyl acetate system is 7:1, 5:1, 3:1 and 1:1 in sequence;
The component 69D is subjected to RP-C 18 semi-preparation liquid phase and then subjected to RP-C 18 column and Sephadx-LH20 (acetone) column chromatography to obtain a compound 8, wherein gradient methanol is used as a solvent in semi-preparation, the volume concentration is sequentially 20%, 40%, 60%, 80% and 100%, and the RP-C 18 column uses methanol-water as an eluting solvent in the volume ratio of 2:1, 3:1, 4:1 and 1:0;
The component 69F is sequentially prepared into compounds 11 and 12 through a gel chromatographic column, an RP-C 18 column and a high performance liquid chromatography, wherein the gel chromatography adopts a chloroform-methanol elution system, the volume ratio is 1:1, the RP-C 18 column adopts methanol-water as an elution solvent, the solvent volume ratio is 3:1, 4:1, 5:1 and 1:0, and the high performance liquid chromatography is prepared by adopting 98% methanol as a solvent with the flow rate of 2ml/min;
The component 69G passes through an RP-C 18 column, an eluting solvent is an acetone-water system, the volume ratio is 4:1, 5:1, 6:1 and 1:0, and then the compound 6 is obtained after Sephadx-LH20 gel column (acetone) column chromatography;
The component EA-4 is subjected to forward silica gel column chromatography for coarse separation to obtain components 1a-1g; component 1a is eluted by adopting an MCI column gradient, and the volume concentration of methanol eluted by the MCI column gradient is 20%, 40%, 60%, 80% and 100% in sequence; purifying the 60% methanol section by Sephadx-LH20 (acetone) column chromatography to obtain compound 7.
Example 3
Antibacterial activity detection of the compound obtained by the preparation method disclosed in example 2:
1. test strain: actinomyces canker (Pseudomonas syringae pv. Actinidae, psa), bacillus cereus, and staphylococcus aureus (Staphylococcus aureus). The strains are all preserved by glycerol tubes, taken out from a refrigerator at the temperature of minus 80 ℃ and are continuously activated twice in fresh sterile LB culture medium in advance for use.
2. The activity test method comprises the following steps: bacteria were inoculated in LB medium for activation, and were shake-cultured on a shaker at 37℃and 170rpm/min to logarithmic growth phase. Diluting the bacterial liquid to 2X 10- 6 CFU/mL by using LB culture medium, taking the cultured bacterial liquid, and adding 100 mu l of the bacterial liquid into a sterile 96-well plate. Samples and controls were diluted to 200 μm with LB medium. Test compounds are respectively dissolved in DMSO to prepare mother solutions of 200mM, the mother solutions are diluted to 200 mu M by LB culture medium, 100 mu L of diluted sample solution is added into each well of a 96-well plate, and after standing culture is carried out for 12-14 hours in a 37 ℃ incubator, the growth condition of the thalli is observed. Three groups of parallel samples were established, LB medium containing 0.5% DMSO was used as negative control, gentamicin and ciprofloxacin, which are common antibacterial agents, were used as positive control, and a blank control group was set. And (3) combining the primary screening result, and further carrying out rescreening on a series of concentration gradients (1.56-100 mu M) of the test compound with the antibacterial activity. Bacteria grow in 96-well plate LB culture medium, white sediment can be generated after a period of time due to large quantity, the holes with bacteria growth are turbid, sediment appears at the bottom, and the concentration of the compound corresponding to the holes without sediment growth is the minimum antibacterial concentration. Finally, the absorbance value corresponding to the wavelength of 600nm is tested by using an enzyme-labeled instrument to verify the accuracy of the MIC value (minimum inhibitory concentration). The activity data are shown in Table-7.
Data on bacteriostatic activity of Compounds 1-12 from Table-7
The data in Table 7 demonstrate that compounds 1-7 show varying degrees of bacteriostasis against kiwi fruit canker, bacillus cereus and Staphylococcus aureus. Among them, the bacteriostatic effect of compounds 2 and 3 is most remarkable, especially for bacillus cereus and staphylococcus aureus, the MIC value is 6.25 μm, and the inhibitory activity for kiwi fruit canker is moderate, and the MIC value is 25 and 12.5 μm, respectively.
Meanwhile, compound 6 also showed remarkable antibacterial activity against Bacillus cereus, and the MIC value was 6.25. Mu.M. According to the results, the compounds 2,3 and 6 have obvious antibacterial effect and can be used as antibacterial agents for preventing and treating the bacterial infection.
Example 4:
this example discloses a tablet comprising any of the compounds disclosed in example 1, further comprising lactose, starch and magnesium stearate.
The preparation method comprises the following steps: mixing the compound, lactose and starch, uniformly wetting with propylene glycol, sieving the wetted mixture, drying, sieving again, adding magnesium stearate, tabletting the mixture, each tablet weighing 250mg, and the compound content being 10mg.
The obtained tablet can be used as antibacterial agent for treating bacterial infection. The daily dose may be from 0.01 to 10mg/kg body weight, preferably from 0.1 to 5mg/kg body weight, and may be administered in one or more administrations.
Example 5:
The embodiment discloses an ampoule agent, which is obtained by mixing one or more of the compounds disclosed in the embodiment 1 with propylene glycol, wherein the content of aromatic cassane diterpenoid compounds is 2% -8%;
The preparation method comprises the following steps: any one of the compounds obtained in examples 1-2 was dissolved in 3 ml of propylene glycol, filtered, and the resulting solution was filled into an ampoule under aseptic conditions.
The obtained ampoule agent can be used as antibacterial agent for treating pathogen infection. The daily dose may be from 0.01 to 10mg/kg body weight, preferably from 0.1 to 5mg/kg body weight, and may be administered in one or more administrations.
Example 6:
This example discloses a capsule comprising 10mg of the compound disclosed in example 1, 187mg of lactose, 3mg of magnesium stearate;
The preparation method comprises the following steps: the compound was mixed with adjuvants, sieved, mixed homogeneously, and the obtained mixture was filled into hard gelatin capsules each weighing 200mg and the active ingredient content was 10mg. The daily dose may be from 0.01 to 10mg/kg body weight, preferably from 0.1 to 5mg/kg body weight, and may be administered in one or more administrations.
The capsule can be used as antibacterial agent for treating germ infection.
The preferred embodiments of the present disclosure have been described in detail above with reference to the accompanying drawings, but the present disclosure is not limited to the specific details of the embodiments described above, and various simple modifications may be made to the technical solutions of the present disclosure within the scope of the technical concept of the present disclosure, and all the simple modifications belong to the protection scope of the present disclosure.
In addition, the specific features described in the foregoing embodiments may be combined in any suitable manner, and in order to avoid unnecessary repetition, the present disclosure does not further describe various possible combinations.
Moreover, any combination between the various embodiments of the present disclosure is possible as long as it does not depart from the spirit of the present disclosure, which should also be construed as the disclosure of the present disclosure.
Claims (9)
1. An aromatised cassane diterpenoid compound of golden phoenix flower, which is characterized by having any one or more of structures shown in formula 7, formula 8, formula 10 and formula 11:
2. The method for extracting the aromatic cassane diterpenoids from the golden pineapple according to claim 1, which is characterized by comprising the steps of crushing stems of the golden pineapple, and carrying out hot reflux extraction in alcohols to obtain total extract; extracting the total extract with ethyl acetate, and repeatedly subjecting the obtained ethyl acetate extract phase to column chromatography.
3. The method for extracting aromatic cassane diterpenoids from golden pineapple as set forth in claim 2, wherein said alcohols include methanol and ethanol.
4. The method for extracting the aromatic cassane diterpenoid compounds from the golden pineapple according to claim 2, which is characterized by comprising the following steps:
Drying stems of the phoenix-tail fern in shade, pulverizing to 30 meshes, heating and refluxing in methanol to obtain an extracting solution, concentrating the extracting solution under reduced pressure to recover methanol to obtain a crude extract, and extracting the crude extract with ethyl acetate to obtain an ethyl acetate extract phase;
Dissolving an ethyl acetate extract phase by using chloroform or acetone, then carrying out column chromatography segmentation and rough separation by using silica gel, and carrying out gradient elution by using a chloroform/acetone system, wherein the volume ratio of the gradient elution of the chloroform/acetone system is sequentially 1:0, 9:1, 8:2, 7:3, 1:1 and 0:1; taking sulfuric acid ethanol solution as a color developing agent, and combining similar fractions according to TLC color development to obtain 8 components EA 1-EA 8;
After the EA2 component is subjected to silica gel column chromatography, carrying out gradient elution by using a petroleum ether/ethyl acetate system, wherein the elution concentrations of the petroleum ether/ethyl acetate system are sequentially 30:1, 25:1, 20:1 and 10:1 in volume ratio, and 8 components 2A-2H are obtained according to the polarity;
Separating the component 2E by RP-C 18 reverse chromatographic column, forward silica gel chromatographic column and Sephadx-LH20 gel chromatographic column to obtain compound 10;
Carrying out forward silica gel column chromatography on the component EA3, carrying out coarse separation by using a petroleum ether-ethyl acetate system, and obtaining 9 components 69A-69G according to the polarity, wherein the volume ratio of the petroleum ether-ethyl acetate system is 7:1, 5:1, 3:1 and 1:1 in sequence;
After preparing a liquid phase from the component 69D through an RP-C 18 half, carrying out chromatography through an RP-C 18 chromatographic column and a Sephadx-LH20 chromatographic column to obtain a compound 8, wherein the solvent used for preparing the liquid phase through the RP-C 18 half is methanol with volume concentration of 20%, 40%, 60%, 80% and 100% in sequence;
The component 69F is sequentially subjected to a chloroform-methanol gel column, an RP-C 18 chromatographic column and a high performance liquid chromatography preparation column in a volume ratio of 1:1 to obtain a compound 11;
After the component EA-4 is subjected to forward silica gel column chromatography and coarse separation, obtaining components 1a-1g according to the polarity; component 1a is eluted by adopting an MCI column gradient, and the volume concentration of methanol eluted by the MCI column gradient is 20%, 40%, 60%, 80% and 100% in sequence; purifying the 60% methanol section by Sephadx-LH20 column chromatography to obtain the compound 7.
5. Use of the aromatic cassane diterpenoid compounds of golden pineapple as described in claim 1 or pharmaceutically acceptable salts thereof for the preparation of an antibacterial agent formulation.
6. The use according to claim 5, wherein the antimicrobial agent formulation is used for the control of kiwifruit canker, bacillus cereus and staphylococcus aureus.
7. The use according to claim 5, wherein the antimicrobial agent formulation is a pharmaceutically acceptable formulation prepared by adding pharmaceutically acceptable excipients according to conventional techniques, and the pharmaceutically acceptable formulation is a solid formulation or a liquid formulation.
8. The use according to claim 7, wherein the solid formulation is a granule, capsule, tablet, pill; the liquid preparation is an injection preparation.
9. The use according to claim 7, wherein the content of the aromatic cassane diterpenoid compound of the golden pineapple or the pharmaceutically acceptable salt thereof in the antibacterial agent preparation is 2% -8% by mass.
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