CN101366713B - Pharmaceutic use of dandelion xylogen restraint gram-positive bacteria - Google Patents
Pharmaceutic use of dandelion xylogen restraint gram-positive bacteria Download PDFInfo
- Publication number
- CN101366713B CN101366713B CN2008101657284A CN200810165728A CN101366713B CN 101366713 B CN101366713 B CN 101366713B CN 2008101657284 A CN2008101657284 A CN 2008101657284A CN 200810165728 A CN200810165728 A CN 200810165728A CN 101366713 B CN101366713 B CN 101366713B
- Authority
- CN
- China
- Prior art keywords
- herba taraxaci
- rufescidride
- chemical compound
- gram
- staphylococcus aureus
- 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.)
- Expired - Fee Related
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to pharmaceutical application of dandelion lignin in inhibiting Gram-positive bacteria. Rufescidride of the invention has obvious efficacy of inhibiting growth of staphylococcus aureus and beta hemolytic streptococcus. The Rufescidride or pharmaceutically acceptable salt of the Rufescidride and medical compositions containing the compounds can be prospectively used for preventing and treating boil, pustule, toxic epidermal decomposition, pneumonia, osteomyelitis, acute myocarditis, endocarditis, meningitis, mastitis, cystitis, pelvic inflammatory disease, urinary tract inflammation, prostatitis, bacteremia, toxic shock syndrome, lymphadenitis, arthritis, pharyngitis, cervicitis and abscess of muscles, skin, urodeum and a central nervous system caused by bacterial infection.
Description
The application is to be on March 13rd, 2007 applying date, and application number is dividing an application of 200710067458.9 Chinese patent application.
Technical field
The present invention relates to medical technical field, particularly, two lignins that the present invention relates to from Herba Taraxaci to separate having of obtaining control staphylococcus aureus and/or beta hemolytic streptococcus catch and officinal salt thereof, its anti-infectives purposes, and the pharmaceutical composition that contains a little chemical compounds of type.Can expect that it is used to prevent and treat staphylococcus aureus and/or beta hemolytic streptococcus infects furuncle, pustule, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, endocarditis, meningitis, mastitis, cystitis, pelvic inflammatory disease, urinary tract inflammation, prostatitis, bacteremia, poisoning gonosome gram syndrome, lymphadenitis, arthritis, pharyngitis, the cervicitis that causes, and muscle, skin, urodeum, central nervous system's abscess.
Technical background
Staphylococcus aureus (Staphylococcus aureus) is the Gram-positive coccus, the staphylococcus aureus (MRSA) in anti-methyl XiLin is the bacterial strain that begins to occur the eighties in 20th century, it is the epiphytotics main source of disease of microorganism in the hospital and clinically, the main infection that causes the people has furuncle, pustule, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, mastitis, cystitis, prostatitis, bacteremia, toxic shock syndrome, lymphadenitis, pharyngitis, cervicitis, pelvic inflammatory disease, and muscle, skin, urodeum, central nervous system's abscess.So be that health is influenced great pathogenic species.Streptococcus (Streptococcus species) is into catenation, amphimicrobian Gram-positive bacillus.Medically common pathogenic streptococcus major part belongs to β haemolysis type.They are present on people's the mucosa of skin, respiratory tract, digestive tract and urodeum, can cause diseases such as skin, respiratory tract and soft tissue infection such as pneumonia, bacteremia, endocarditis, meningitis, urinary tract inflammation and arthritis.
Chinese traditional medicine is a resourceful treasure-house.Wherein many medicinal plants all contain the effect of good restraining staphylococcus aureus (be called for short " golden Portugal bacterium ') and beta hemolytic streptococcus.Herba Taraxaci is feverfew Herba Taraxaci (Taraxacum mongolicum Hand-Mazz also claims Mongolian Herba Taraxaci) or the dry herb that belongs to several plants together, is heat-clearing and detoxifying herb, and the function of heat clearing away, detoxifcation, diuresis, eliminating stagnation is arranged; Cure mainly acute mastitis, furuncle, conjunctival congestion, pharyngalgia, jaundice due to damp-heat and the puckery pain of pyretic stranguria etc.Be usually used in treating diseases such as acute mastitis, lymphadenitis, furuncle carbuncle toxin, acute conjunctivitis, cold, fever, acute tonsillitis, acute bronchitis, hepatitis, swollen capsulitis and urinary tract infection clinically.Herba Taraxaci mainly contains triterpenes, phytosterol, doubly
Chemical compounds such as terpene lactones, Coumarins, flavonoid, phenolic acids, carotenoid and fatty acid.Its pharmacological action has anti-inflammation, change, hepatic cholagogic, immunomodulating and antitumor etc.At present, injection, tablet and the granule etc. that utilize the Herba Taraxaci single medicinal material to make are widely used in clinical, treat various diseases associated with inflammation and have obtained curative effect preferably.
Herba Taraxaci has stronger heat-clearing toxin-expelling functions, have higher research and development and be worth, but domestic research to Herba Taraxaci mainly rests on its crude extract, especially lacks the effective substance correlational study.Domestic correlational study report and patent generally all are with the application of compound recipe form, rare from Herba Taraxaci effective component extracting 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 Mongolian Herba Taraxaci (T.mongolicum).Domestic chemical constitution study report to the Dandelion plant is very few, quote the chemical constituent 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 constituent of Mongolian Herba Taraxaci T.mongolicum and [has reached the clouds Bao Yanyan more, Zhu Lili, Zheng Junhua, Cai Shaoqing, Xiao Yue, the Herba Taraxaci The Chemical Constituents. Chinese Pharmaceutical Journal, 1997,32,584-586; Reach the clouds Bao Yanyan, Zhang Yonglin, Cai Shaoqing, Zheng Junhua, Herba Taraxaci The Chemical Constituents, the Navy General Hospital journal, 1998,11,167-169], be divided into 5 chemical compounds: cupreol, Quercetin, caffeic acid, chlorogenic acid and luteolin-7-oxygen-glucoside, and other chemical constituent it be not immediately clear.For understanding the chemical composition 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 key component is flavonoid glycoside and polyphenol compound.
Summary of the invention
The purpose of this invention is to provide a kind of lignin chemical compound Mongolia taraxeric acid A and Rufescidride and officinal salt and antibacterial application that from Compositae Herba Taraxaci 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 staphylococcus aureus and/or beta hemolytic streptococcus, pustule, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, endocarditis, meningitis, mastitis, cystitis, pelvic inflammatory disease, urinary tract inflammation, prostatitis, bacteremia, toxic shock syndrome, lymphadenitis, arthritis, pharyngitis, cervicitis, and muscle, skin, urodeum, the medicine of central nervous system's abscess and medicine or the health product purposes relevant with above-mentioned disease;
Another object of the present invention has provided the pharmaceutical composition that contains lignin chemical compound of the present invention.
The present invention prepares following lignin chemical compound 1 and 2 by extracting from the feverfew Herba Taraxaci, concrete structure is as follows:
Mongolia taraxeric acid A (chemical compound 1) Rufescidride (chemical compound 2)
Two lignin chemical compound titles are respectively:
Chemical compound 1 (Mongolian taraxeric acid A): 6,9,10-trihydroxy-xanthene-1,2-dicarboxylic acids;
Chemical compound 2 (Rufescidride).
Lignin chemical compound 1 and 2 is mainly derived from each position of feverfew Herba Taraxaci, preferably from Herba Taraxaci (claiming Mongolian Herba Taraxaci again) (Taraxacum mongolicum Hand-Mazz), alkali ground Herba Taraxaci (claiming magnificent Herba Taraxaci again) (Taraxacum sinicum Kitag), hot river Herba Taraxaci (claiming white edge Herba Taraxaci again) (Taraxacumplatypecidum Diels), Herba Taraxaci ohwiani (Taraxacum ohwianumKitag), anti-luxuriant Herba Taraxaci (Taraxacum grypodon Dahlst), common Herba Taraxaci medical material rhizome on Xingan's Herba Taraxaci 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 Herba Taraxaci (claim not only Mongolian Herba Taraxaci) (Taraxacum mongolicum Hand-Mazz) and/or alkali ground Herba Taraxaci (but also claiming magnificent Herba Taraxaci) (Taraxacum sinicum Kitag).
Characteristics of the present invention are, from feverfew Herba Taraxaci rhizome, leaf, flower separates its effective site of purifying in the position, and therefrom obtain two monomeric compounds, through the chemical assay structure is lignin chemical compound 1 and 2, and find that it has very strong inhibition staphylococcus 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 staphylococcus aureus and beta hemolytic streptococcus, include but not limited to furuncle, pustule, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, endocarditis, meningitis, mastitis, cystitis, pelvic inflammatory disease, urinary tract inflammation, prostatitis, bacteremia, toxic shock syndrome, lymphadenitis, arthritis, pharyngitis, cervicitis, and muscle, skin, urodeum, central nervous system's abscess.
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 Herba Taraxaci plant.The inventor is to the high polarity position of this plant extract, obtain this by multiple positive and negative phase chromatography means and effectively suppress staphylococcus aureus and active two the activation things 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 constitution do not report for forefathers with and anhydride (Rufescidride).
Medical material among the present invention can be the arbitrary position of home-made Dandelion plant in any one, promptly can be Herba Taraxaci (claiming Mongolian Herba Taraxaci again) (Taraxacum mongolicum Hand-Mazz), alkali ground Herba Taraxaci (claiming magnificent Herba Taraxaci again) (Taraxacum sinicum Kitag), hot river Herba Taraxaci (claiming white edge Herba Taraxaci again) (Taraxacum platypecidumDiels), Herba Taraxaci ohwiani (Taraxacum ohwianumKitag), anti-luxuriant Herba Taraxaci (Taraxacum grypodon Dahlst), common Herba Taraxaci medical material on Xingan's Herba Taraxaci Chinese drug markets such as (Taraxacum falcilobumKitag), can be dry product or bright product, it can be the root of Herba Taraxaci medical material plant, stem, leaf, flower, seed, skin, fruit also can be their mixture.Preferred herb.The more preferably herb part of Herba Taraxaci (claim not only Mongolian Herba Taraxaci) (Taraxacum mongolicum Hand-Mazz) and/or alkali ground Herba Taraxaci (but also claiming magnificent Herba Taraxaci) (Taraxacum sinicum Kitag).All be called for short Herba Taraxaci in the present invention's the description.
The inventor finds that two lignin compositions that the present invention obtains have the function that suppresses staphylococcus aureus and beta hemolytic streptococcus growth; Can be used to prevent and treat the furuncle, pustule, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, endocarditis, meningitis, mastitis, cystitis, pelvic inflammatory disease, urinary tract inflammation, prostatitis, bacteremia, toxic shock syndrome, lymphadenitis, arthritis, pharyngitis, the cervicitis that cause by staphylococcus aureus and beta hemolytic streptococcus, and muscle, skin, urodeum, central nervous system's abscess and medicine or the health product purposes relevant with above-mentioned symptom or disease; Thereby may develop the anti-infection drug compositions.This pharmaceutical composition can be made various dosage forms with the routine techniques in the pharmaceutical field, as tablet, granule, capsule, oral liquid, drop 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 polariscope of Polax-2L type in Japan and is measured; Infrared spectrum IR is measured by Bruker Vector-22 HONGGUANG spectrometer, through the KBr tabletting; Ultraviolet spectra is measured with Shimadzu 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-400 MHz); Electrospray Mass Spectrometry ESI-MS is measured by the BrukerEsquire300+ 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 petroleum ether 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 polyamide (14-30 order and 100-200 order); Polydextran gel Sephadex LH-20 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 uviol lamp with 254nm and 365nm; Developer iodine vapor, 10% sulphuric acid-ethanol, 2% ferric chloride-methanol, phosphomolybdic acid and bromocresol green solution.
Liquid phase: Waters series of high efficiency chromatograph of liquid comprises 2695 piece-rate systems (quaternary pump, column oven and automatic sampler), 2996 ultraviolet diode matrix detectors, Empower chromatographic run software.Chromatographic column:
The C18 chromatographic column (4.6mm * 250mm), 5 μ m.
1.2 plant origin and evaluation
Purchase in the Haozhou, Anhui August calendar year 2001 with the Herba Taraxaci medical material for extracting, be accredited as the herb of Mongolian Herba Taraxaci (Taraxacum mongolicumHand-Mazz.) by pharmaceutical college of Zhejiang University Chinese medicine and associate professor Chen Liurong of natural drug research department.For comparing content Herba Taraxaci (Mongolian Herba Taraxaci) (Taraxacum mongolicumHand-Mazz), alkali ground Herba Taraxaci (magnificent Herba Taraxaci) (Taraxacum sinicum Kitag), hot river Herba Taraxaci (white edge Herba Taraxaci) (Taraxacum platypecidumDiels), Herba Taraxaci ohwiani (Taraxacumohwianum Kitag), anti-luxuriant Herba Taraxaci (Taraxacum gypodon Dahlst), each 20 gram of Xingan's Herba Taraxaci (Taraxacum 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 Herba Taraxaci (Mongolian Herba Taraxaci) (Taraxacum mongolicum Hand-Mazz) and each 100 gram of the bright product of alkali ground Herba Taraxaci (magnificent Herba Taraxaci) (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 alcohol boiling water, and extracting solution cooling back merges, and gets the thick crude extract of 462 gram sepias through concentrating under reduced pressure.With the crude extract dissolve with methanol, the D-101 macroporous resin is mixed sample, methanol is removed in decompression on Rotary Evaporators, with the discolour silica gel is desiccant, 40 ℃ of vacuum dryings spend the night, and application of sample is collected 50% methanol-water eluting position in the good D-101 post of water balance, eluent is concentrated into dried, the reuse distilled water is made behind the suspension and is distributed extraction with petroleum ether, ethyl acetate, n-butyl alcohol successively.Get 3 grams after each organic layer evaporated under reduced pressure respectively, 32 grams, 127 gram extractum, surplus is the water position.
1.4 the separation and purification of ethyl acetate
Get ethyl acetate extract extractum 82 gram silica gel (200-300 order) posts (900 gram), (1:0 → 0:1) is the eluant gradient elution with chloroform-methanol, be divided into 6 positions (F1-F6) according to thin layer chromatography TLC situation, wherein F2 (4 gram) crosses silicagel column (100 gram), with the petroleum ether-ethyl acetate (eluting of 8:1 → 0:1), check through thin layer chromatography TLC, petroleum ether-ethyl acetate (5:1) eluting person is contained same composition, obtain Rufescidride (24.6 milligrams) through recrystallization, F6 (1 gram) uses polydextran gel Sephadex LH 20 (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
1.5.1 the structure of Rufescidride is identified: chemical compound 2 is red amorphous powder, from EI-MS,
1H-NMR and
13The molecular formula that the C-NMR spectrum can be released chemical compound is C
18H
8O
7Its IR spectrum (1798,1737cm
-1) show that having two carbonyls in the molecule exists with the form of anhydride; While is m/z 264[M-CO-CO in the EI-MS spectrum
2]
+Fragment ion peak also confirmed to exist in the chemical compound anhydride.
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 chemical 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 chemical compound 2 have the how typical characteristic 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 chemical compound is Rufescidride.People such as S A Souza da Silva in 2004 separate from feverfew Cordia rufescens first and obtain this chemical compound.
Refescidride: red unformed powder; C
18H
8O
7UV λ
Max(methanol): 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:
Chemical 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/z 353[M-H]
-, Duo 18 mass units than Rufescidride, can judge that therefore Rufescidride may be the product of chemical compound 1 dehydration, promptly chemical compound 1 may be hydrolyzed into the chemical compound of two carboxylic acids for 9 and 9 ' anhydride of Rufescidride.1721cm among the IR
-1The absworption peak at place and chemical compound 1 bromocresol green show blueness has also proved to have hydroxy-acid group in the chemical compound.
13C-NMR and DEPT spectrum show in the chemical compound 1 to have 18 sp
2The carbon of hydridization comprises 5 methines, two carbonyls of 5 company's oxygen quaternary carbons;
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 chemical 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 chemical 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 chemical compound 1 is the arylnaphthalene lignans, at last by the aryl found with document how lignans compare and can identify chemical compound 1 and be Mongolian taraxeric acid A.
Be illustrated as the relevant sketch map of HMBC of chemical compound 1
Mongolia taraxeric acid A: red unformed powder; C
18H
10O
8UV λ
Max(ultraviolet): 196,226,276,317,373nm; Infrared IR
(em
-1): 3400,1721,1608,1520; ESI-MSm/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
6100MHz) 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 chemical 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 " development test medicine, be to utilize the trial drug that is added in the cup of Oxford to be diffused into inoculation to have in the culture medium of test organisms, thereby suppress the growth of antibacterial, come the antibacterial activity of confirmed test medicine by the diameter that detects the inhibition zone that around the cup of Oxford, forms.
2.2 detect bacterium:
Staphylococcus 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;
Norfloxacin: 1.25mg/ml;
Mongolia taraxeric acid A (chemical compound 1): 5.0mg/ml; Rufescidride (chemical 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 and but solidify naturally.
(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 stand cloth is in the plate with M-H agar bottom.
2.4.3, treat culture medium solidifying after, in each plate, evenly put the upright test medicinal liquid 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 (chemical compound 1) and Rufescidride (chemical compound 2)
Antibacterial circle diameter (mm) to the standard pathogenic bacterium
2.5 experiment conclusion:
By adopting the antibacterial activity in vitro of " micro-dilution method " the research chemical compound 1 and the 2 pairs of staphylococcus aureuses and beta hemolytic streptococcus.The result shows: the chemical compound 1 and the 2 pairs of staphylococcus aureuses and beta hemolytic streptococcus have better antibacterial activity.Illustrate that it is potential inhibition gram-positive bacteria active substance, have further exploitation and be worth.
Lignin of the present invention Mongolia Herba Taraxaci A and Rufescidride can combine with spoke material or carrier pharmaceutically commonly used, prepare medicine with infection that prevention and treatment cause by staphylococcus aureus and beta hemolytic streptococcus and pharmaceutical composition or guarantor and build product.Above-mentioned various kinds of drug compositions or health care can be adopted drug forms such as tablet, capsule, injection, aerosol, suppository, membrane, drop pill, externally-applied liniment, ointment.
Lignin of the present invention Mongolia taraxeric acid A and Rufescidride can also infect the medicine of associated conditions and crude drug thereof such as cephalo-type, Macrolide and sulfonamides such as husky magnitude types of drugs with the similar gram-positive bacteria of the staphylococcus 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 compositions of associated conditions effect or compound preparation, can expect becomes treatment gram-positive bacteria catch medicine or health product.Above-mentioned various kinds of drug compositions or health product can adopt drug forms such as tablet, capsule, injection, aerosol, suppository, membrane, drop pill, comprise the conventional preparation of pharmaceutics general knowledge that employing has now been generally acknowledged and various slow release, controlled release form or the nanometer formulation that gets.
Embodiment 3:Chemical compound 1 and 2 comparison in five kinds of Dandelion plant roots and stems and the aerial parts stem and leaf
Herba Taraxaci (Mongolian Herba Taraxaci) (Taraxacum mongolicumHand-Mazz), alkali ground Herba Taraxaci (magnificent Herba Taraxaci) (Taraxacum sinicum Kitag), hot river Herba Taraxaci (white edge Herba Taraxaci) (TaraxacumplatypecidumDiels), Herba Taraxaci ohwiani (Taraxacum ohwianumKitag), anti-luxuriant Herba Taraxaci (Taraxacum grypodon Dahlst), each 20 gram of Xingan's Herba Taraxaci (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 piece-rate systems comprise quaternary pump, column oven automatic sampler; 2996 ultraviolet diode matrix are picked up the survey device, Empower chromatographic run software and
The C18 chromatographic column (4.6mm * 250mm), 5 μ m) chemical 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 methanol to scale, filter with 0.45 μ m filter membrane.
The preparation of standard solution: accurately take by weighing respectively 10. milligrams of chemical compounds 1 and 2, add 8 ml methanol ultrasonic dissolutions respectively, add the standard reserving solution that methanol is made into 0.5 mg/ml more separately.With methanol according to 1:1,1:10,1:50,1:100 is mixed with standard solution, cold preservation is standby.Prepare the standard solution of chemical compound 1 and 2 separately with method.Reagent: methanol is HPLC level (Merk production), and water is redistilled water.Chromatographic condition: use
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.Mobile phase: methanol/0.1%HAc=75:25 isocratic elution.
Content measuring: with extraction solvent, standard solution, confession test agent difference sample introduction, record chromatogram.With the corresponding concentration of standard solution curve plotting of peak area, calculate the range of linearity, correlation coefficient 〉=0.998.Calculate chemical compound 1 and 2 content respectively from standard curve.
Discovery content is as shown in the table:
Mongolian taraxeric acid A (chemical compound 1) and Rufescidride (chemical compound 2) content in the common Herba Taraxaci of table 3
| Chemical compound 1 content (%) | Chemical compound 2 content (%) | |
| Mongolia's Herba Taraxaci (Herba Taraxaci) rhizome part | 1.2 | 1.0 |
| Mongolia's Herba Taraxaci (Herba Taraxaci) aerial parts stem and leaf | 1.4 | 1.2 |
| Alkali ground Herba Taraxaci (magnificent Herba Taraxaci) herb | 1.3 | 0.9 |
| Hot river Herba Taraxaci (white edge Herba Taraxaci) herb | 1.7 | 1.1 |
| The Herba Taraxaci ohwiani herb | 1.4 | 1.9 |
| Anti-luxuriant Herba Taraxaci herb | 1.0 | 1.3 |
| Xingan's Herba Taraxaci herb | 1.1 | 1.6 |
The result shows: Mongolian Herba Taraxaci rhizome and aerial parts all contain chemical compound of the present invention, and alkali ground Herba Taraxaci, hot river Herba Taraxaci, Herba Taraxaci ohwiani, anti-luxuriant Herba Taraxaci, the chemical compound 1 and 2 that all contains different content in Xingan's Herba Taraxaci, illustrate that Mongolian taraxeric acid A and Rufescidride are the characteristic chemical constituents in the Compositae Dandelion plant, are not limited to Mongolian Herba Taraxaci so use this platymiscium to comprise, alkali ground Herba Taraxaci, hot river Herba Taraxaci, Herba Taraxaci ohwiani, anti-luxuriant Herba Taraxaci, Xingan's Herba Taraxaci 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) chemical compound 1 and 2 comparison
Herba Taraxaci (Mongolian Herba Taraxaci) (TaraxacummongolicumHand-Mazz), the bright product of alkali ground Herba Taraxaci (magnificent Herba Taraxaci) (Taraxacum sinicum Kitag) each 100 restrain and identify by professor Chen Liurong of Zhejiang University.
With this high performance liquid chromatography of water (Waters HPLC, 2695 piece-rate systems comprise quaternary pump, column oven automatic sampler; 2996 ultraviolet diode matrix detectors, Empower chromatographic run software and
The C18 chromatographic column (4.6mm * 250mm), 5 μ m) chemical compound 1 and 2 has been carried out content detection.
Content measuring:, write down chromatogram with extraction solvent, the difficult product solution of mark, for test agent sample introduction respectively.With the corresponding concentration of standard solution curve plotting of peak area, calculate the range of linearity, correlation coefficient 〉=0.998.Calculate the content of chemical compound 1 and 2 respectively from standard curve.Concrete operations are with embodiment 3.
Mongolian taraxeric acid A (chemical compound 1) and the contrast of Rufescidride (chemical compound 2) content in two kinds of Herba Taraxaci dry products of table 4 and the bright product
| Chemical compound 1 content (%) | Chemical compound 2 content (%) | |
| The bright product of Mongolia's Herba Taraxaci (Herba Taraxaci) | 1.5 | 1.3 |
| Mongolia's Herba Taraxaci (Herba Taraxaci) dry product | 1.4 | 1.2 |
| The bright product of alkali ground Herba Taraxaci (magnificent Herba Taraxaci) | 1.3 | 1.0 |
| Alkali ground Herba Taraxaci (magnificent Herba Taraxaci) dry product | 1.3 | 0.9 |
The result shows: all contain the chemical compound 1 and 2 of different content in the dry product of Mongolian Herba Taraxaci and alkali ground Herba Taraxaci and the bright product, content there is no big difference.Illustrate and cover taraxeric acid A and Rufescidride exists and content is comparatively stable in Compositae Dandelion plant, so use dry product of this platymiscium and bright product can prepare the anti-gram-positive bacteria medicine that contains Mongolian taraxeric acid A and Rufescidride of the presently claimed invention.
Claims (2)
1. the Rufescidride of lignin compound that has following structure is used to prepare prevention or treats staphylococcus aureus and/or the purposes of the medicine of the related symptoms of beta hemolytic streptococcus infection or disease.
2. according to the purposes of claim 1, wherein the related symptoms of infection of staphylococcus aureus or disease are meant furuncle, pustule, toxicity epidermis decomposition, pneumonia, osteomyelitis, acute myocarditis, mastitis, cystitis, prostatitis, bacteremia, toxic shock syndrome, lymphadenitis, pharyngitis, cervicitis, pelvic inflammatory disease, and muscle, skin, urodeum, central nervous system's abscess; Related inflammation was pneumonia, bacteremia, endocarditis, meningitis, urinary tract inflammation and arthritis disease due to beta hemolytic streptococcus infected.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101657284A CN101366713B (en) | 2007-03-13 | 2007-03-13 | Pharmaceutic use of dandelion xylogen restraint gram-positive bacteria |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101657284A CN101366713B (en) | 2007-03-13 | 2007-03-13 | Pharmaceutic use of dandelion xylogen restraint gram-positive bacteria |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2007100674589A Division CN100471851C (en) | 2007-03-13 | 2007-03-13 | Lignin in dandelion, its bacteria-resisting activity and use for medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101366713A CN101366713A (en) | 2009-02-18 |
| CN101366713B true CN101366713B (en) | 2011-05-04 |
Family
ID=40410805
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008101657284A Expired - Fee Related CN101366713B (en) | 2007-03-13 | 2007-03-13 | Pharmaceutic use of dandelion xylogen restraint gram-positive bacteria |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101366713B (en) |
-
2007
- 2007-03-13 CN CN2008101657284A patent/CN101366713B/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| souza da silva, et al."A new arylnaphthalene type ligan from cordiarufescensA.DC.(Boraginaceac)".ARKIVOC VI.2004,(VI),54-58. |
| souza da silva, et al."A new arylnaphthalene type ligan from cordiarufescensA.DC.(Boraginaceac)".ARKIVOC VI.2004,(VI),54-58. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101366713A (en) | 2009-02-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Moawad et al. | Phytochemical investigation of Cycas circinalis and Cycas revoluta leaflets: moderately active antibacterial biflavonoids | |
| Ganzon et al. | 4-O-Caffeoylquinic acid as an antioxidant marker for mulberry leaves rich in phenolic compounds | |
| Deng et al. | Anneslea fragrans Wall. ameliorates ulcerative colitis via inhibiting NF-κB and MAPK activation and mediating intestinal barrier integrity | |
| Xing et al. | Simulated gastrointestinal tract metabolism and pharmacological activities of water extract of Scutellaria baicalensis roots | |
| Lai et al. | Antioxidant, anti-inflammatory and antiproliferative activities of Kalanchoe gracilis (L.) DC stem | |
| Liu et al. | An in vivo and in vitro assessment of the anti-inflammatory, antinociceptive, and immunomodulatory activities of Clematis terniflora DC. extract, participation of aurantiamide acetate | |
| Iverson et al. | Glutathione S-transferase inhibitory, free radical scavenging, and anti-leishmanial activities of chemical constituents of Artocarpus nobilis and Matricaria chamomilla | |
| CN101343225A (en) | Preparation method for high-purity di-coffee mesitoyl quinine acid compounds | |
| Menković et al. | Bioactive compounds of endemic species Sideritis raeseri subsp raeseri grown in national park Galicica | |
| CN100491364C (en) | Sesquiterplactone in dandelion and its use of resisting Gram's positive bacteria | |
| KR20140021882A (en) | Composition having activating effect for ampk | |
| Chen et al. | A review: antimicrobial properties of several medicinal plants widely used in Traditional Chinese Medicine | |
| CN101112409A (en) | Preparation of phenolic acid valid target in dandelion and use thereof for inhibiting influenza virus | |
| Sahli et al. | An ecological approach to discover new bioactive extracts and products: the case of extremophile plants | |
| Sendker et al. | Phenylpropanoid-substituted procyanidins and tentatively identified procyanidin glycosides from hawthorn (Crataegus spp.) | |
| Chen et al. | Antibacterial, anti‐inflammatory, analgesic, and hemostatic activities of Acanthopanax trifoliatus (L.) merr | |
| CN108774276B (en) | Viburnum sargentii fruit lignan extract and active ingredient and application thereof | |
| CN100471851C (en) | Lignin in dandelion, its bacteria-resisting activity and use for medicine | |
| Zhong et al. | Qihuzha granule attenuated LPS-induced acute spleen injury in mice via Src/MAPK/Stat3 signal pathway | |
| CN102659802A (en) | Preparation method of coumarin lignan compounds and application of coumarin lignan compounds in resisting marine fouling | |
| CN100471847C (en) | Eremophilane containing chlorine atom in Heizituowu and its anti-biotic and cell-toxin activity | |
| CN104382968A (en) | Method for extracting common andrographis paniculata total lactone, pharmaceutical composition of andrographis paniculata total lactone and use of pharmaceutical composition | |
| Gawrońska-Grzywacz et al. | Biological activity of new flavonoid from Hieracium pilosella L. | |
| CN101366713B (en) | Pharmaceutic use of dandelion xylogen restraint gram-positive bacteria | |
| CN101214237B (en) | Pharmaceutical use of dandelion xylogen acid for inhibiting acetylcholine esterase |
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: 20110504 Termination date: 20120313 |