CN101024640A - Lignin in dandelion, its bacteria-resisting activity and use for medicine - Google Patents
Lignin in dandelion, its bacteria-resisting activity and use for medicine Download PDFInfo
- Publication number
- CN101024640A CN101024640A CN 200710067458 CN200710067458A CN101024640A CN 101024640 A CN101024640 A CN 101024640A CN 200710067458 CN200710067458 CN 200710067458 CN 200710067458 A CN200710067458 A CN 200710067458A CN 101024640 A CN101024640 A CN 101024640A
- Authority
- CN
- China
- Prior art keywords
- taraxacum
- compound
- streptococcus
- mongolian
- disease
- 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
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention relates to a lignin compound that could prevent yellow staphylococcal bacteria and B type hemolytic streptococcus, and the medicine combination of the compound. The invention of lignin Morgan dandehon herb acid A and Rufescidride has obviously effect restraining yellow staphylococcal and B type hemolytic streptococcus. It is also respected to prevent the diseases caused by them, like boil, blain, toxicity epidermis necrolysis, pneumonia, etc.
Description
Technical field
The present invention relates to medical technical field, particularly, two xylogen that the present invention relates to from taraxacum to separate having of obtaining control streptococcus aureus and/or beta hemolytic streptococcus catch and pharmacologically acceptable salt thereof, its anti-infectives purposes, and the pharmaceutical composition that contains these compounds.Can expect that it is used to prevent and treat streptococcus aureus and/or beta hemolytic streptococcus infects furuncle, warts, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, endocarditis, meningitis, mazoitis, urocystitis, pelvic inflammatory disease, urinary tract inflammation, prostatitis, microbemia, toxic shock syndrome, poradenolymphitis, sacroiliitis, pharyngitis, the trachelitis that causes, and the abscess of muscle, skin, urodeum, central nervous system.
Technical background
Streptococcus aureus (Staphylococcus aureus) is the Gram-positive coccus, the streptococcus aureus (MRSA) in anti-methyl XiLin is the bacterial strain that begins to occur the eighties in 20th century, it is the epiphytotics main pathogeny of microorganism in the hospital and clinically, the main infection that causes the people has furuncle, warts, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, mazoitis, urocystitis, prostatitis, microbemia, toxic shock syndrome, poradenolymphitis, pharyngitis, trachelitis, pelvic inflammatory disease, and muscle, skin, urodeum, the abscess of central nervous system.So be that HUMAN HEALTH is influenced great pathogenic species.Suis (Streptococcus species) is into catenation, amphimicrobian Gram-positive bacillus.Medically common pathogenic suis major part belongs to β haemolysis type.They are present on people's the mucous membrane of skin, respiratory tract, digestive tube and urodeum, can cause diseases such as skin furan, respiratory tract and soft tissue infection such as pneumonia, microbemia, endocarditis, meningitis, urinary tract inflammation and sacroiliitis.
Chinese traditional medicine is a resourceful treasure-house.Wherein many medicinal plants all contain the effect of good restraining streptococcus aureus (being called for short " golden Portugal bacterium ") and beta hemolytic streptococcus.Taraxacum is feverfew taraxacum (Taraxacum mongolicum Hand-Mazz also claims Mongolian taraxacum) or the dry herb that belongs to several plants together, is heat-clearing and detoxifying herb, and the function of heat-clearing, detoxifcation, diuresis, dissipating bind is arranged; Cure mainly acute mastitis, furunculosis, hot eyes, pharyngalgia, jaundice due to damp-heat and heat and drench puckery pain etc.Be usually used in treating diseases such as acute mastitis, lymphadenitis, malignant boil carbuncle toxin, acute conjunctivitis, cold, fever, acute tonsillitis, acute bronchitis, hepatitis, swollen capsulitis and urinary tract infections clinically.Taraxacum mainly contains compounds such as triterpenes, phytosterol, sesquiterpene lactones class, coumarins, flavonoid, phenolic acids, carotenoid and fatty acid.Its pharmacological action has antisepsis and anti-inflammation, anti-oxidant, hepatic cholagogic, immunomodulatory and antitumor etc.At present, injection, tablet and the granule etc. that utilize the taraxacum single medicinal material to make are widely used in clinical, treat various diseases associated with inflammation and have obtained curative effect preferably.
Taraxacum has stronger heat-clearing toxin-expelling functions, have higher research and development and be worth, but domestic research to taraxacum mainly rests on its crude extract, especially lacks the effective substance correlative study.Domestic correlative study report and patent generally all are to use with the compound form, rare from taraxacum extracting effective components and the report studied at its bacteriostatic activity.More comprehensive abroad to the chemical constitution study of common dandelion (Taraxacum officinale), find that it mainly contains sesquiterpene, triterpene and flavones ingredient, the pharmacologically active report is less, and does not see the chemical constitution study report at the public English of Mongolia (T.mongolicum).Domestic chemical constitution study to the Dandelion plant reports that it is few, quote the chemical ingredients of common dandelion Taraxacum officinale, at present the result for retrieval seminar that finds to reach the clouds has carried out the research report to the chemical ingredients of Mongolian taraxacum T.mongolicum and [has reached the clouds Bao Yanyan more, Zhu Lili, Zheng Junhua, Cai Shaoqing, Xiao Yue, taraxacum The Chemical Constituents Chinese Pharmaceutical Journal, 1997,32,584-586; Reach the clouds Bao Yanyan, Zhang Yonglin, Cai Shaoqian, Zheng Junhua, taraxacum The Chemical Constituents, the Navy General Hospital journal, 1998,11,167-169], be divided into 5 compounds: β-Gu Zaichun, Quercetin, coffic acid, chlorogenic acid and luteolin-7-oxygen-glucoside, and other chemical ingredients it be not immediately clear.For understanding the chemical constitution of each polar fraction of T.mongolicum, we have carried out the fitochemical studies of system to it.Result of study shows that high polarity position chief component is flavonoid glycoside and polyphenolic compound.
Summary of the invention
The purpose of this invention is to provide a kind of lignin compound Mongolia taraxeric acid A and Rufescidride and pharmacologically acceptable salt and antibacterial application that from composite family taraxacum plant, obtains;
Another object of the present invention has provided The compounds of this invention is used to prepare prevention and treats the furuncle that is caused by streptococcus aureus and/or beta hemolytic streptococcus, warts, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, endocarditis, meningitis, mazoitis, urocystitis, pelvic inflammatory disease, urinary tract inflammation, prostatitis, microbemia, toxic shock syndrome, poradenolymphitis, sacroiliitis, pharyngitis, trachelitis, and muscle, skin, urodeum, the medicine of the abscess of central nervous system and medicine or the healthcare products purposes relevant with above-mentioned disease;
Another object of the present invention has provided the pharmaceutical composition that contains lignin compound of the present invention.
The present invention prepares following lignin compound 1 and 2 by extracting from the feverfew taraxacum, concrete structure is as follows:
Mongolia taraxeric acid A (compound 1) Rufescidride (compound 2)
Two lignin compound titles are respectively:
Compound 1 (Mongolian taraxeric acid A): 6,9,10-trihydroxy--xanthene-1,2-dicarboxylic acid;
Compound 2 (Rufescidride).
Lignin compound 1 and 2 is mainly derived from each position of feverfew taraxacum, preferably from taraxacum (claiming Mongolian taraxacum again) (Taraxacum mongolicum Hand-Mazz), alkali ground taraxacum (claiming magnificent taraxacum again) (Taraxacum sinicumKitag), hot river taraxacum (claiming white edge taraxacum again) (TaraxacumplatypecidumDiels), Herba Taraxaci ohwiani (Taraxacum ohwianmKitag), anti-luxuriant taraxacum (Taraxacum grypodon Dahlst), common taraxacum medicinal material rhizome on the Xingan taraxacum Chinese drug markets such as (Taraxacum falcilobum Kitag), leaf, flower comprises preparing in its dry product and the bright product and getting.The herb part of preferred taraxacum (claim not only Mongolian taraxacum) (Taraxacum mongolicum Hand-Mazz) and/or alkali ground taraxacum (but also claiming magnificent taraxacum) (Taraxacum sinicum Kitag).
Characteristics of the present invention are, from feverfew taraxacum rhizome, leaf, flower separates its efficient part of purifying in the position, and therefrom obtain two monomeric compounds, through the chemical assay structure is lignin compound 1 and 2, and find that it has very strong inhibition streptococcus aureus and beta hemolytic streptococcus effect, provide and to have expected to be used to prepare to cause or relevant physiological change or treatment of diseases medicine and prevention and health care product with gram-positive bacteria especially streptococcus aureus and beta hemolytic streptococcus, include but not limited to furuncle, warts, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, endocarditis, meningitis, mazoitis, urocystitis, pelvic inflammatory disease, urinary tract inflammation, prostatitis, microbemia, toxic shock syndrome, poradenolymphitis, sacroiliitis, pharyngitis, trachelitis, and muscle, skin, urodeum, the abscess of central nervous system.
Specific embodiments
Plant is in the past discovered and is contained triterpenes, coumarins, phenolic acids (flavonoid that comprises phenolic hydroxy group), sesquiterpenoids, phytosterol, carotenoid and long-chain fat acid compounds in the taraxacum plant.The inventor is to the high polarity position of this plant milk extract, obtain this by multiple positive and negative phase chromatography means and effectively suppress streptococcus aureus and active two active compounds of beta hemolytic streptococcus, and through integration analysis such as infrared, mass spectrum, ultraviolet and NMR (Nuclear Magnetic Resonance) spectrum derive the Mongolian taraxeric acid A of a lignin compound that its chemical structure do not report for forefathers with and acid anhydrides (Rufescidride).
Medicinal material among the present invention can be the arbitrary position of home-made Dandelion plant in any one, promptly can be taraxacum (claiming Mongolian taraxacum again) (Taraxacum mongolicum Hand-Mazz), alkali ground taraxacum (claiming magnificent taraxacum again) (Taraxacum sinicum Kitag), hot river taraxacum (claiming white edge taraxacum again) (Taraxacum platypecidum Diels), Herba Taraxaci ohwiani (Taraxacum ohwianumKitag), anti-luxuriant taraxacum (Taraxacum grypodon Dahlst), common taraxacum medicinal material on the Xingan taraxacum Chinese drug markets such as (Taraxacum falcilobumKitag), can be dry product or bright product, it can be the root of taraxacum medicinal material plant, stem, leaf, flower, seed, skin, fruit also can be their mixture.Preferred herb.The more preferably herb part of taraxacum (claim not only Mongolian taraxacum) (Taraxacum mongolicum Hand-Mazz) and/or alkali ground taraxacum (but also claiming magnificent taraxacum) (Taraxacum sinlcum Kitag).All be called for short taraxacum in the present invention's the specification sheets.
The inventor finds that two lignin compositions that the present invention obtains have the function that suppresses streptococcus aureus and beta hemolytic streptococcus growth; Can be used to prevent and treat the furuncle, warts, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, endocarditis, meningitis, mazoitis, urocystitis, pelvic inflammatory disease, urinary tract inflammation, prostatitis, microbemia, toxic shock syndrome, poradenolymphitis, sacroiliitis, pharyngitis, the trachelitis that cause by streptococcus aureus and beta hemolytic streptococcus, and the abscess and medicine or the healthcare products purposes relevant with above-mentioned symptom or disease of muscle, skin, urodeum, central nervous system; Thereby may develop the anti-infection drug composition.This pharmaceutical composition can be made various formulations with the routine techniques in the pharmacy field, as tablet, granule, capsule, oral liquid, dripping pill, injection, transdermal patch, aerosol etc.
Further specify the present invention below by embodiment.The following embodiment of mandatory declaration is used to illustrate the present invention rather than limitation of the present invention.Essence according to the present invention all belongs to the scope of protection of present invention to the simple modifications that the present invention carries out.
Embodiment 1:Mongolia taraxeric acid A and Rufescidride separate:
1.1 instrument and reagent
Fusing point is measured with micro-fusing point instrument (production of Beijing Imtech), and temperature is not proofreaied and correct; Optically-active is produced on the automatic polarimeter of Polax-2L type in Japan and is measured; Infrared spectra IR is by Bruker Vector-22 determination of infrared spectroscopy, through the KBr compressing tablet; UV spectrum is measured with Shimdzu UV-240 ultraviolet spectrophotometer; Proton nmr spectra
1H-NMR, carbon-13 nmr spectra
13C-NMR and 2D NMR measure (tetramethylsilane ether TMS is interior mark) by INOVA type NMR spectrometer with superconducting magnet (VARIANINOVA-400MHz); Electrospray ionization mass spectrum ESI-MS is measured by the BrukerEsquire3000+ mass spectrograph, and column chromatography is produced by Haiyang Chemical Plant, Qingdao with silica GF254 (10-40 order) with silica gel (100-200,200-300 and 300-400 order) and thin-layer chromatography; Agents useful for same is analytical pure, and wherein the sherwood oil boiling range is 60-90 ℃; Thin layer preparative chromatography (PTLC) the aluminium foil silica-gel plate of Merck company; Column chromatography adopts the biochemical plastic molding and processing plant of Taizhou, Zhejiang Province city road and bridge tetramethyl product with polymeric amide (14-30 order and 100-200 order); The poly-grain gel Sephadex LH-20 in Portugal adopts Sweden Amersham Pharmacia Biotech AB company product; Reverse phase silica gel RP-18 adopts the Chromatorex product of Japanese Fuji Silysia Chemical company; MCI is a Mitsubishi chemical company product, and thin plate (TLC) detects the ultraviolet lamp with 254nm and 365nm; Developer iodine vapor, 10% sulfuric acid-ethanol, 2% iron trichloride-methyl alcohol, phospho-molybdic acid and tetrabromo-mcresolsulfonphthalein solution.
Liquid phase: Waters series of high efficiency liquid chromatograph comprises 2695 separation systems (quaternary pump, column oven and automatic sampler), 2996 ultraviolet diode matrix detectors, Empower chromatographic run software.Chromatographic column: Symmetry
The C18 chromatographic column (4.6mm * 250mm), 5 μ m.
1.2 plant origin and evaluation
Purchase in the Bozhou, Anhui August calendar year 2001 with the taraxacum medicinal material for extracting, be accredited as the herb of Mongolian taraxacum (Taraxacum mongolicumHand.-Mazz.) by pharmaceutical college of Zhejiang University Chinese medicine and associate professor Chen Liurong of natural drug research department.Use taraxacum (Mongolian taraxacum) (Taraxacum mongolicumHand.-Mazz) for comparing content, alkali ground taraxacum (magnificent taraxacum) (Taraxacum sinicum Kitag), hot river taraxacum (white edge taraxacum) (Taraxacum platypecidumDiels), Herba Taraxaci ohwiani (Taraxacumohwianum Kitag), anti-luxuriant taraxacum (Taraxacum grypodon Dahlst), each 20 gram of Xingan taraxacum (Taraxcum falcilobum Kitag) dry product are taught in August, 2003～2004 by the Peng Hua of Kunming plant institute of the Chinese Academy of Sciences and are assisted to gather and identify year July., identify than gathering from the Tian Mu Shan Mountain, Zhejiang Province for fresh and dried product content by associate professor Chen Liurong of pharmaceutical college of Zhejiang University than taraxacum (Mongolian taraxacum) (Taraxacum mongolicum Hand.-Mazz) and each 100 gram of the bright product of alkali ground taraxacum (magnificent taraxacum) (Taraxacumsinicum Kitag).
1.3 extract and separate
Sample shines dry grinding (5.0 kilograms of dry weights) back and carries twice with heat under the 75% industrial spirit boiling water, and extracting solution cooling back merges, and gets the thick crude extract of 462 gram browns through concentrating under reduced pressure.With the crude extract dissolve with methanol, the D-101 macroporous resin is mixed sample, methyl alcohol is removed in decompression on Rotary Evaporators, with the discolour silica gel is siccative, 40 ℃ of vacuum-dryings are spent the night, and application of sample is collected 50% methanol-water wash-out position in the good D-101 post of water balance, elutriant is concentrated into dried, makes behind the suspension with distilled water again and distribute extraction with sherwood oil, ethyl acetate, propyl carbinol successively.Get 3 grams after each organic layer evaporated under reduced pressure respectively, 32 grams, 127 gram medicinal extract, surplus is the water position.
1.4 ethyl acetate separation and purification
Get ethyl acetate extract medicinal extract 82 gram silica gel (200-300 order) posts (900 gram), with chloroform-methanol ( was 0: 1 in 1: 0) is the eluent gradient elution, be divided into 6 positions (F1-F6) according to thin-layer chromatography TLC situation, wherein F2 (4 gram) crosses silicagel column (100 gram), with petroleum ether-ethyl acetate ( was 0: 1 in 8: 1) wash-out, check through thin-layer chromatography TLC, petroleum ether-ethyl acetate (5: 1) wash-out person is contained same composition, obtain Rufescidride (24.6 milligrams) through recrystallization, F6 (1 gram) uses dextrane gel Sephadex LH20 (100mL) column chromatography, with methanol-eluted fractions, and obtain Mongolian taraxeric acid A (12.2 milligrams) through water-pure recrystallization.
1.5 structure is identified
1.5.1Rufescidride structure identify: compound 2 is red amorphous powder, from EI-MS,
1H-NMR and
13The molecular formula that the C-NMR spectrum can be released compound is C
18H
8O
7Its IR spectrum (1798,1737cm
-1) show that having two carbonyls in the molecule exists with the form of acid anhydrides; While is m/z264[M-CO-CO in the EI-MS spectrum
2]
+Fragment ion peak also confirmed to exist in the compound acid anhydrides.
1In the H-NMR spectrum, three unimodal aryl hydrogen signal δ 8.79 (s, H-6 '), 8.07 (s, and the bimodal signal δ 7.63 of ortho-hydrogens H-7) and on 6.72 (s, H-3 ') and two phenyl ring (d, J=8.8Hz, H-6) and 7.44 (d, J=8.8Hz H-5), are aided with
13C-NMR and DEPT spectrum can be released has 18 carbon in the compound (II-31): 5 aryl tertiary carbons, 13 quaternary carbons [comprise 5 even oxygen quaternary carbon δ 138.6 (C-3), 144.0 (C-4), 151.8 (C-2 '), (147.5 C-4 ') and 142.3 (C-5 ')] as can be seen compound 2 have the how characteristic feature of lignans of aryl, by carefully compare [S A Souza da Silva etc. with document, A new arylnaphthalene type lignan from Cordiarufescens A DC (Boraginaceas), ARKIVOC, 2004,54-58], determine that compound is Rufescidride.People such as SA Souza da Silva in 2004 separate from feverfew Cordia rufescens first and obtain this compound.
Refescidride: red unformed powder; C
18H
8O
7UV λ
Max(methyl alcohol): 208,222,241,313,393nm; Proton nmr spectra
1H-NMR (DMSO-d
6, 400MHz) δ 8.79 (1H, unimodal, H-6 '), 8.07 (1H, unimodal, H-7), 7.63 (1H, bimodal, J=8.8Hz, H-6), 7.44 (1H, bimodal, J=8.8Hz, H-5), 6.72 (1H, unimodal, H-3 '); Carbon-13 nmr spectra
13C-NMR (DMSO-d
6, 100MHz) δ 163.9 (s, C-9), 163.6 (s, C-9 '), 151.8 (s, C-2 '), (147.5 s, C-4 '), 143.9 (s, C-4), 142.3 (s, C-5 '), 138.6 (s, C-3), 133.4 (s, C-7 '), 128.2 (s, C-1), (125.7 s, C-8 '), 123.8 (s, C-8), 124.6 (d, C-7), 122.9 (d, C-6), 121.4 (d, C-5), 115.0 (d, C-6 '), 110.8 (s, C-2), 109.2 (s, C-1 '), 103.3 (d, C-3 ').
1.5.2 the structure of Mongolian taraxeric acid A is identified:
Compound 1 is a red powder shape solid, UV,
1H-NMR and
13The C-NMR spectrum is closely similar with compound R ufescidride, and ESI-MS shows molecular ion peak m/z353[M-H]
-, Duo 18 mass units than Rufescidride, can judge that therefore Rufescidride may be the product of compound 1 dehydration, promptly compound 1 may be hydrolyzed into the compound of two carboxylic acids for 9 and 9 ' acid anhydrides of Rufescidride.1721cm among the IR
-1The absorption peak at place and compound 1 tetrabromo-mcresolsulfonphthalein show blueness has also proved to have hydroxy-acid group in the compound.
13C-NMR and DEPT spectrum show in the compound 1 to have 18 sp
2The carbon of hydridization comprises 5 methynes, 5 company's oxygen quaternary carbons and two carbonyls;
1In the H-NMR spectrum, (unimodal, H-7), 7.40 is (unimodal for the unimodal signal δ 8.05 of three aryl hydrogen of demonstration, H-6 ') and two bimodal signal δ 7.46 of 6.62 (unimodal, H-3 ') and phenyl ring ortho-hydrogens (bimodal, J=8.8Hz, H-6) and 7.25 (bimodal, J=8.8Hz, H-5).Figure below has shown several main coherent signals in the HMBC spectrogram, and wherein H-6 and C-2 have long-range relevant between C-4 and the C-7; Between H-5 and C-1 and the C-3 long-range relevant and H-7 and C-2 are arranged, C-6, C-8 has between C-9 and the C-9 ' in the long-range related description compound 1 and has the dicarboxyl naphthalene ring.H-6 ' and C-4 ' have between C-2 and the C-7 ' to have phenyl ring that one or three oxygen replace in the long-range coherent signal explanation compound 1 that exists between long-range relevant and H-3 ' and C-1 ' and the C-5 ' and link to each other with how encircling.Therefore can determine that compound 1 is the arylnaphthalene lignans, at last by the aryl found with document how lignans compare and can identify compound 1 and be Mongolian taraxeric acid A.
Be illustrated as the relevant synoptic diagram of HMBC of compound 1
Mongolia taraxeric acid A: red unformed powder; C
18H
10O
8UV λ
Max(ultraviolet): 196,226,276,317,373nm; Infrared IRv
Max KBr(cm
-1): 3400,1721,1608,1520; ESI-MS m/z:353[M-H]
-Proton nmr spectra
1H-NMR (DMSO-d
6, 400MHz) δ 8.05 (1H, unimodal, H-7), 7.46 (1H, bimodal, J=8.8Hz, H-6), 7.40 (1H, unimodal, H-6 '), 7.25 (1H, bimodal, J=8.8Hz, H-5), 6.62 (1H, unimodal, H-3 '); Carbon-13 nmr spectra
13C-NMR (DMSO-d
6, 100MHz) δ 171.6 (s, C-9 '), 167.8 (s, C-9), 148.6 (s, C-4 '), (146.4 s, C-2 '), 142.1 (s, C-5 '), 141.8 (s, C-4), 136.7 (s, C-3), 128.4 (d, C-7), 126.2 (s, C-8), 125.8 (s, C-1), 123.3 (s, C-2), 123.0 (s, C-7 '), (122.3 s, C-8 '), 121.4 (d, C-6), 120.0 (d, C-5), (112.5 d, C-6 '), 109.7 (s, C-1 '), 103.9 (d, C-3 ').
Embodiment 2:Lignin compound 1 and 2 suppresses the gram-positive bacteria ability and detects
2.1 principle:
Adopt the antibacterial activity in vitro of " cup-plate method " research trial thing, be to utilize to be added in that the test drug diffusion has in the substratum of test organisms in the cup of Oxford to inoculation, thereby suppress the growth of bacterium, come the anti-microbial activity of confirmed test medicine by the diameter that detects the inhibition zone that around the cup of Oxford, forms.
2.2 detect bacterium:
Streptococcus aureus 26003-23 is available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute.
Beta hemolytic streptococcus 32210 is available from Nat'l Pharmaceutical ﹠ Biological Products Control Institute.
2.3 trial drug:
The DMSO:DMSO solvent control;
Norfloxicin: 1.25mg/ml;
Mongolia taraxeric acid A (compound 1): 5.0mg/ml; Rufescidride (compound 2): 5.0mg/ml; Sample all dissolves with DMSO.
2.4 method and step:
2.4.1, the preparation of M-H agar, M-H meat soup and test organisms liquid.
2.4.2, the preparation of two dish:
(1), M-H agar bottom: get sterilization M-H agar liquid naturally cooling and solidify.
(2), M-H agar bacterium layer: get bacterium liquid 150 μ l and 30mlM-H agar mixing.Get about 5ml and contain bacterium liquid agar, evenly spread out cloth in plate with M-H agar bottom.
2.4.3, treat culture medium solidifying after, in each plate, evenly put the upright test soup Oxford cup of filling it up with.
2.4.4, put 37 ℃ and cultivated 24 hours.
2.4.5, use the vernier caliper measurement antibacterial circle diameter.
Mongolian taraxeric acid A of table 2 (compound 1) and Rufescidride (compound 2) are to the antibacterial circle diameter (mm) of standard pathogenic bacterium
| Bacterial classification | The experiment medicine | |||
| DMSO | 1 (5.0mg/ml) | Norfloxicin (2.5mg/ml) | 2 (5.0mg/ml) | |
| Streptococcus aureus-26003 beta hemolytic streptococcus-10102 | Unrestraint 9.56 | 13.97 16.45 | 30.1 28.65 | 12.42 14.13 |
2.5 experiment conclusion:
By adopting the antibacterial activity in vitro of " micro-dilution method " the research compound 1 and the 2 pairs of streptococcus aureuses and beta hemolytic streptococcus.The result shows: compound 1 and 2 streptococcus aureuses and beta hemolytic streptococcus have better antibacterial activity.Illustrate that it is that potential suppresses the gram-positive bacteria active substance, has further exploitation and is worth.
Xylogen Mongolia taraxeric acid A of the present invention and Rufescidride can combine with spoke material or carrier pharmaceutically commonly used, prepare the medicine and pharmaceutical composition or the healthcare products that have prevention and treat the infection that is caused by streptococcus aureus and beta hemolytic streptococcus.Above-mentioned various kinds of drug composition or healthcare products can adopt drug forms such as tablet, capsule, injection, aerosol, suppository, film, pill, externally-applied liniment, ointment.
Xylogen of the present invention Mongolia taraxeric acid A and Rufescidride can also infect the medicine of associated conditions and bulk drug thereof such as cephalosporin, Macrolide and sulfamido such as husky magnitude types of drugs with the similar gram-positive bacteria of the streptococcus aureus that has now gone on the market, beta hemolytic streptococcus inhibitor and/or other treatment and unite use, prepare and have the treatment gram-positive bacteria and infect active composition of associated conditions effect or compound preparation, can expect becomes treatment gram-positive bacteria catch medicine or healthcare products.Above-mentioned all kinds of compositions or healthcare products can adopt drug forms such as tablet, capsule, injection, aerosol, suppository, film, pill, comprise the conventional preparation of pharmaceutics general knowledge that employing has now been generally acknowledged and various slowly-releasings, controlled release form or the nanometer formulation that gets.
Implement 3:Compound 1 and 2 comparison in five kinds of Dandelion plant roots and stems and the over-ground part cauline leaf
Taraxacum (Mongolian taraxacum) (Taraxacum mongolicum Hand-Mazz), alkali ground taraxacum (magnificent taraxacum) (Taraxacum sinicum Kitag), hot river taraxacum (white edge taraxacum) (Taraxacumplatypecidum Diels), Herba Taraxaci ohwiani (Taraxacum ohwianum Kitag), anti-luxuriant taraxacum (Taraxacum grypodn Dahlst), each 20 gram of Xingan taraxacum (Taraxacum falcilobum Kitag) dry product are gathered by professor Peng Hua of Kunming plant institute of the Chinese Academy of Sciences and are identified.
With this high performance liquid chromatography of water (Waters HPLC, 2695 separation systems comprise quaternary pump, column oven automatic sampler; 2996 ultraviolet diode matrix detectors, Empower chromatographic run software and Symmetry
The C18 chromatographic column (4.6mm * 250mm), 5 μ m) compound 1 and 2 has been carried out content detection.
Handle for test agent: the sample that dries in the shade after pulverizing respectively takes by weighing 0.5 gram (± 0.1 milligram), puts 25 milliliters of volumetric flasks, adds 20 ml methanol, 25～30 ℃ ultrasonic 60 minutes down, add methyl alcohol to scale, filter with 0.45 μ m filter membrane.
The preparation of standardized solution: accurately take by weighing respectively 10.0 milligrams of compounds 1 and 2, add 8 ml methanol ultrasonic dissolutions respectively, add the standard reserving solution that methyl alcohol is made into 0.5 mg/ml more separately., 1: 10,1: 50, be mixed with standardized solution, refrigerate standby at 1: 100 according to 1: 1 with methyl alcohol.Prepare the standardized solution of compound 1 and 2 separately with method.Reagent: methyl alcohol is HPLC level (Merk production), and water is redistilled water.Chromatographic condition: use Symmetry
The C18 chromatographic column (4.6mm * 250mm), 5 μ m, 30 ℃ of column temperatures detect wavelength: 254nm, flow velocity: 0.8 ml/min, sample size: 20 μ l.Moving phase: methyl alcohol/0.1%HAc=75: 25 isocratic elutions.
Content measuring: with extraction solvent, standard solution, confession test agent difference sample introduction, record color atlas.With the corresponding concentration of standard solution curve plotting of peak area, calculate linearity range, relation conefficient 〉=0.998.Calculate the content of compound 1 and 2 respectively from typical curve.
Discovery content is as shown in the table:
Mongolian taraxeric acid A (compound 1) and Rufescidride (compound 2) content in the common taraxacum of table 3
| Compound 1 content (%) | Compound 2 content (%) | |
| Mongolia's taraxacum (taraxacum) rhizome part | 1.2 | 1.0 |
| Mongolia's taraxacum (taraxacum) over-ground part cauline leaf | 1.4 | 1.2 |
| Alkali ground taraxacum (magnificent taraxacum) herb | 1.3 | 0.9 |
| Hot river taraxacum (white edge taraxacum) herb | 1.7 | 1.1 |
| The Herba Taraxaci ohwiani herb | 1.4 | 1.9 |
| Anti-luxuriant taraxacum herb | 1.0 | 1.3 |
| Xingan's taraxacum herb | 1.1 | 1.6 |
The result shows: Mongolian taraxacum rhizome and over-ground part all contain compound of the present invention, and alkali ground taraxacum, hot river taraxacum, Herba Taraxaci ohwiani, anti-luxuriant taraxacum, the compound 1 and 2 that all contains different content in the Xingan taraxacum, illustrate that Mongolian taraxeric acid A and Rufescidride are the characteristic chemical constituents in the composite family Dandelion plant, are not limited to Mongolian taraxacum so use this platymiscium to comprise, alkali ground taraxacum, hot river taraxacum, Herba Taraxaci ohwiani, anti-luxuriant taraxacum, Xingan taraxacum etc. can prepare the anti-gram-positive bacteria medicine that contains Mongolian taraxeric acid A and Rufescidride of the presently claimed invention.
Embodiment 4:Two kinds of Dandelion plant stem-leafs (in bright product and the dry product) compound 1 and 2 comparison
Taraxacum (Mongolian taraxacum) (Taraxacum mongolicum Hand-Mazz), each 100 gram of the bright product of alkali ground taraxacum (magnificent taraxacum) (Taraxacum sinicum Kitag) are identified by professor Chen Liurong of Zhejiang University.
With this high performance liquid chromatography of water (Waters HPLC, 2695 separation systems comprise quaternary pump, column oven automatic sampler; 2996 ultraviolet diode matrix detectors, Empower chromatographic run software and Symmetry
The C18 chromatographic column (4.6mm * 250mm), 5 μ m) compound 1 and 2 has been carried out content detection.
Content measuring: will extract menstruum, standard solution, supply test agent sample introduction respectively, record color atlas.With the corresponding concentration of standard solution curve plotting of peak area, calculate linearity range, relation conefficient 〉=0.998.Calculate the content of compound 1 and 2 respectively from typical curve.Concrete operations are with embodiment 3.
Mongolian taraxeric acid A (compound 1) and the contrast of Rufescidride (compound 2) content in two kinds of taraxacum dry products of table 4 and the bright product
| Compound 1 content (%) | Compound 2 content (%) | |
| The bright product of Mongolia taraxacum (taraxacum) | 1.5 | 1.3 |
| Mongolia's taraxacum (taraxacum) dry product | 1.4 | 1.2 |
| The bright product of alkali ground taraxacum (magnificent taraxacum) | 1.3 | 1.0 |
| Alkali ground taraxacum (magnificent taraxacum) dry product | 1.3 | 0.9 |
The result shows: all contain the compound 1 and 2 of different content in dry product of Mongolian taraxacum and alkali ground taraxacum and the bright product, content there is no big difference.Illustrate that Mongolian taraxeric acid A and Rufescidride exist and content is comparatively stable in composite family Dandelion plant, so use dry product of this platymiscium and bright product can prepare the anti-gram-positive bacteria medicine that the present invention wants Mongolian taraxeric acid A of containing of ball and Rufescidride.
Claims (8)
1. the xylogen and pharmacologically acceptable salt or its solvate that have following structure:
Compound 1 (Mongolian taraxeric acid A).
2. the described compound of claim 1, its name is called: 6,9,10-three hydroxyls-xanthene-1,2-dicarboxylic acid.
3. according to claim 1 or 2 described lignin compounds, and the analogue (compound 2:Rufescidride) with following structure is used to prepare the purposes of the medicine of related symptoms that prevention or treatment streptococcus aureus and/or beta hemolytic streptococcus infect or disease:
Rufescidride。
4. according to the purposes of claim 3, related symptoms or disease that wherein golden yellow staphylococcus infects are meant furuncle, warts, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, mazoitis, urocystitis, prostatitis, microbemia, toxic shock syndrome, poradenolymphitis, pharyngitis, trachelitis, pelvic inflammatory disease, and the abscess of muscle, skin, urodeum, central nervous system; Due to beta hemolytic streptococcus infects related inflammation be meant that skin is held up, respiratory tract and soft tissue infection such as pneumonia, microbemia, endocarditis, meningitis, urinary tract inflammation and arthritis disease.
5. one kind is used to prevent or treat streptococcus aureus and/or the related symptoms of beta hemolytic streptococcus infection or the pharmaceutical composition of disease, it contains as described lignin compound of the claim 1～3 of the treatment significant quantity of activeconstituents or their pharmacologically acceptable salt, with and composition thereof and pharmaceutically acceptable carrier.
6. according to the pharmaceutical composition of claim 5, it is that prevention and treatment streptococcus aureus and/or beta hemolytic streptococcus infect furuncle, warts, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, endocarditis, meningitis, mazoitis, urocystitis, pelvic inflammatory disease, urinary tract inflammation, prostatitis, microbemia, toxic shock syndrome, poradenolymphitis, sacroiliitis, pharyngitis, the trachelitis that causes, and the abscess of muscle, skin, urodeum, central nervous system.
7. according to the pharmaceutical composition of claim 5 or 6, it can be tablet, granule, capsule, oral liquid, lotion, suppository, liniment, injection, transdermal patch or aerosol, can also adopt the known controlled release of modern pharmaceutical circle or slow release formulation or nanometer formulation.
8. according to the preparation approach of the described compound of claim 1～3, it is mainly derived from the arbitrary position of home-made Dandelion plant in any one, promptly can be taraxacum (claiming Mongolian taraxacum again) (Taraxacummongolicum Hand-Mazz), alkali ground taraxacum (claiming magnificent taraxacum again) (Taraxacum sinicumKitag), hot river taraxacum (claiming white edge taraxacum again) (Taraxacum platypecidumDiels), Herba Taraxaci ohwiani (Taraxacum ohwianumKitag), anti-luxuriant taraxacum (Taraxacum grypodonDahlst), common taraxacum medicinal material on the Xingan taraxacum Chinese drug markets such as (Taraxacum falcilobum Kitag); Can be dry product or bright product; Can be root, stem, leaf, flower, seed, skin, the fruit of taraxacum medicinal material plant, also can be their mixture and herb part.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100674589A CN100471851C (en) | 2007-03-13 | 2007-03-13 | Lignin in dandelion, its bacteria-resisting activity and use for medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100674589A CN100471851C (en) | 2007-03-13 | 2007-03-13 | Lignin in dandelion, its bacteria-resisting activity and use for medicine |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008101657284A Division CN101366713B (en) | 2007-03-13 | 2007-03-13 | Pharmaceutic use of dandelion xylogen restraint gram-positive bacteria |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101024640A true CN101024640A (en) | 2007-08-29 |
| CN100471851C CN100471851C (en) | 2009-03-25 |
Family
ID=38743331
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2007100674589A Expired - Fee Related CN100471851C (en) | 2007-03-13 | 2007-03-13 | Lignin in dandelion, its bacteria-resisting activity and use for medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100471851C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105582036A (en) * | 2014-11-06 | 2016-05-18 | 株式会社Lg生活健康 | Composition for promoting synthesis of hyaluronic acid comprising Taraxacum herbs extracts and the use thereof |
| CN111084836A (en) * | 2019-12-17 | 2020-05-01 | 清华德人西安幸福制药有限公司 | Application of combination of thermionic acid and antibiotics in intervention of antibacterial action against pathogenic bacteria |
| CN111205253A (en) * | 2020-02-11 | 2020-05-29 | 广西壮族自治区中国科学院广西植物研究所 | Cortex illicii alcohol C, and preparation method and application thereof |
-
2007
- 2007-03-13 CN CNB2007100674589A patent/CN100471851C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105582036A (en) * | 2014-11-06 | 2016-05-18 | 株式会社Lg生活健康 | Composition for promoting synthesis of hyaluronic acid comprising Taraxacum herbs extracts and the use thereof |
| CN111084836A (en) * | 2019-12-17 | 2020-05-01 | 清华德人西安幸福制药有限公司 | Application of combination of thermionic acid and antibiotics in intervention of antibacterial action against pathogenic bacteria |
| CN111084836B (en) * | 2019-12-17 | 2021-12-10 | 清华德人西安幸福制药有限公司 | Application of combination of thermionic acid and antibiotics in intervention of antibacterial action against pathogenic bacteria |
| CN111205253A (en) * | 2020-02-11 | 2020-05-29 | 广西壮族自治区中国科学院广西植物研究所 | Cortex illicii alcohol C, and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100471851C (en) | 2009-03-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Moawad et al. | Phytochemical investigation of Cycas circinalis and Cycas revoluta leaflets: moderately active antibacterial biflavonoids | |
| Dall'Agnol et al. | Antimicrobial activity of some Hypericum species | |
| US9283256B2 (en) | Antibacterial composition comprising Salvia extracts | |
| Xing et al. | Simulated gastrointestinal tract metabolism and pharmacological activities of water extract of Scutellaria baicalensis roots | |
| CN104761565B (en) | Myrtle ketone compound and application thereof in preparation of antibacterial medicines | |
| Li et al. | Spectrum-effect relationship of antioxidant and tyrosinase activity with Malus pumila flowers by UPLC-MS/MS and component knock-out method | |
| Negi et al. | Evaluation of antimicrobial activity of Bauhinia purpurea leaves under in vitro conditions | |
| Amer et al. | Novel aminoalkaloids from European mistletoe (Viscum album L.) | |
| Iverson et al. | Glutathione S-transferase inhibitory, free radical scavenging, and anti-leishmanial activities of chemical constituents of Artocarpus nobilis and Matricaria chamomilla | |
| Zhang et al. | Flavonoids and its derivatives from Callistephus chinensis flowers and their inhibitory activities against alpha-glucosidase | |
| Alajmi et al. | Comparative anticancer and antimicrobial activity of aerial parts of Acacia salicina, Acacia laeta, Acacia hamulosa and Acacia tortilis grown in Saudi Arabia | |
| Qiu et al. | Kaempferol separated from Camellia oleifera meal by high-speed countercurrent chromatography for antibacterial application | |
| CN100491364C (en) | Sesquiterplactone in dandelion and its use of resisting Gram's positive bacteria | |
| Miran et al. | Characterization and Antibacterial Activity of Phthalides from the Roots of the Medicinal Herb Levisticum officinale WDJ Koch. | |
| Ghasemian-Yadegari et al. | Evaluation of phytochemical, antioxidant and antibacterial activity on Astragalus Chrysostachys Boiss. Roots | |
| Labed et al. | Amino acid-sesquiterpene lactone conjugates from the aerial parts of Centaurea pungens and evaluation of their antimicrobial activity | |
| Aihaiti et al. | Non-volatile compounds of Hyssopus cuspidatus Boriss and their antioxidant and antimicrobial activities | |
| Jayalakshmi et al. | Isolation and characterization of bioactive compounds from Euphorbia cotinifolia | |
| CN100471851C (en) | Lignin in dandelion, its bacteria-resisting activity and use for medicine | |
| CN100471847C (en) | Eremophilane containing chlorine atom in Heizituowu and its anti-biotic and cell-toxin activity | |
| Zhao et al. | Traditional uses, chemical composition and pharmacological activities of Alstonia R. Br.(Apocynaceae): A review | |
| Gawrońska-Grzywacz et al. | Biological activity of new flavonoid from Hieracium pilosella L. | |
| CN103889430B (en) | A kind of Flos Lonicerae extract, comprise its medical composition and its use | |
| CN101050177B (en) | Black purple Tuowusu A and medical application in restraining grampostive bacteria | |
| CN101366713B (en) | Pharmaceutic use of dandelion xylogen restraint gram-positive bacteria |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20090325 Termination date: 20110313 |