CN107144589A - A kind of method that anaerobic bacteria Inhibitors form Chinese Traditional Medicinal Herbs are screened based on Fe Co Ni nano-probes - Google Patents
A kind of method that anaerobic bacteria Inhibitors form Chinese Traditional Medicinal Herbs are screened based on Fe Co Ni nano-probes Download PDFInfo
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- CN107144589A CN107144589A CN201710228480.0A CN201710228480A CN107144589A CN 107144589 A CN107144589 A CN 107144589A CN 201710228480 A CN201710228480 A CN 201710228480A CN 107144589 A CN107144589 A CN 107144589A
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N24/00—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects
- G01N24/08—Investigating or analyzing materials by the use of nuclear magnetic resonance, electron paramagnetic resonance or other spin effects by using nuclear magnetic resonance
- G01N24/088—Assessment or manipulation of a chemical or biochemical reaction, e.g. verification whether a chemical reaction occurred or whether a ligand binds to a receptor in drug screening or assessing reaction kinetics
Abstract
A kind of method that anaerobic bacteria Inhibitors form Chinese Traditional Medicinal Herbs are screened based on Fe Co Ni nano-probes, belongs to tcm development applied technical field.The present invention dependent on set up based on prepares Fe Co Ni nano-probes be used for screen suppression anaerobic bacteria Chinese medicine preparation method.The characteristics of paramagnetic Fe Co Ni nano-probes prepared can be specifically bound to object bacteria is coated with using antibody, the influence using Fe Co Ni paramagnetic properties to the NMR relaxation time detects whether contain object bacteria in sample.Paramagnetic Fe Co Ni nano-probes, NMR relaxation time showing outlet sexual intercourse within the specific limits, that is nanometer Fe Co Ni contents are big, the nuclear magnetic resonance spin Lattice Relaxation Time and transverse relaxation time value of sample are smaller, detection object bacteria can be quantified in certain limit, so that the fungistatic effect of indirect assessment Chinese medicine preparation.This method can be used for the recipe determination for having the Chinese medicine of inhibitory action to anaerobic bacteria, accelerate the development rate of tcm product.
Description
Technical field
The present invention relates to a kind of screening technique of Chinese medicine preparation.
Background technology
Antibiotic simultaneously, will also result in human body infringement, influence liver, renal function, gastrointestinal reaction etc. in sterilization.Abuse is anti-
Raw element may cause the generation of some bacterial resistance phenomenons, and the treatment to infection can become very difficult.At present, almost without one
Plant antibacterials and resistance phenomenon is not present.Chinese medicine and formula of the exploitation with antibacterial action have positive effect.
Many Chinese medicines and magistral medicines have antibacterial and anti-inflammation functions, and some medium-height grass the effective elements of the medicines and molecular structure etc. are also
Through studying clear whole or in part.The main component berberine of such as coptis and golden cypress stop dysentery(Berberine), radix scutellariae antibacterial
Main component baicalein etc..A host of facts prove, the medicine that ancient Chinese working people is accumulated by long-term practice
Legacy is extremely abundant, extremely valuable.We should value the great treasure-house of this motherland's medicine and pharmacology, make great efforts to excavate, be subject to
Improve, can therefrom develop the Chinese medicine with antibacterial and anti-inflammation functions, can replace or part substitution antibiotic.
Anaerobic bacteria be a class under anaerobic than the bacterium grown in aerobic environment, and can not be with the presence of air
In the case of the bacterium that grows.This kind of bacterium lacks complete metabolism enzyme system, and its energetic supersession is carried out in the way of anaerobic fermentation.
It can cause the infection of human body different parts, including appendicitis, cholecystitis, tympanitis, mouth infection, endocarditis, osteomyelitis,
A variety of diseases such as peritonitis.It is usually in sterilizing in Chinese medicine new formulation procedures of traditional exploitation for certain anaerobic bacteria
Traditional Chinese medicinal components are added after inoculation of medium anaerobic bacteria, are cultivated in special anaerobic culture box.Sampled again after a period of time into
Row line culture, calculates clump count, so that it is determined that whether certain Chinese medicine compositing formula has bacteriostasis.Line culture is also required to detesting
Cultivated in oxygen incubator, and cultivation cycle at least takes several days, therefore whole cycle is long, efficiency is low.This method is asked for above-mentioned
Inscribe a kind of rapid screening method of Chinese medicine preparation of invention.
The general principle of this method:Monoclonal antibody or antigen molecule are by Covalent bonding together, and this combination will not change
Monoclonal antibody, the immunological characteristic of antigen and bioactivity, specific monoclonal antibody only can be with specific antigen knots
Close.And Fe-Co-Ni materials have ferromagnetism, its outer layer has multiple unpaired electrons, with high saturation and magnetic intensity, in grain
Footpath it is small to a certain extent when, it may appear that paramagnetic and superparamagnetic characteristic, Fe-Co-Ni nano materials can be to the nuclear-magnetisms of surrounding water molecules
The influence of resonance spin-lattice relaxation time is very big, the effect with amplification nuclear magnetic resonance relaxation signals.It is very micro
The NMR relaxation time that Fe-Co-Ni nano materials will result in water declines to a great extent.Therefore can be by building Fe-Co-Ni
Nano-probe, detects whether there is object bacteria from the angle of magnetic resonance, so that the bacteriostasis of indirect assessment traditional Chinese medicine ingredients.
Key step:
1)Prepared by Fe-Co-Ni nano-probes.Commercially paramagnetic Fe-Co-Ni nano materials, can also be by other
Method prepares nano level Fe-Co-Ni.Using silane coupler, its formula is:Y(CH2)nSiX3.Herein, n is 0-3;X is can
The group of hydrolysis;Y is organo-functional group.X is typically chloro, methoxyl group, ethyoxyl, acetoxyl group etc., when these groups are hydrolyzed
That is generation silanol (Si (OH)3), and combined with inorganic substances, form siloxanes.Y is vinyl, amino, epoxy radicals, methyl-prop
Alkene acyloxy, sulfydryl.These reactive groups can react and combine with organic substance.Therefore, can be by using silane coupler
" molecular bridge " is erected between inorganic substances and the interface of organic substance, the material of two kinds of property great disparities is linked together raising again
The effect of the performance and increase adhesive strength of condensation material.By silane coupler react can obtain surface modification amination or
The Fe-Co-Ni nano materials of carboxylated.Further by coupled antibody, surface-functionalized, formation specific immunity spy can be achieved
Pin, closes unnecessary avtive spot, can separate excessive antibody after centrifugation, you can to obtain the Fe- of resistance modification
Co-Ni nano-probes.
2)The sample cell made using polystyrene material carries out Chinese medicine screening.Polystyrene material and ELISA Plate class
Seemingly, detecting probe surface antibody can be combined on the surface of polystyrene material due to suction-operated, still, and the antibody of detecting probe surface is inhaled
The speed of polystyrene material surface is attached to compared with the speed of detecting probe surface antibody binding object bacteria, the former is slow-footed more,
Both are competitive relations.Therefore, the culture medium of the anaerobic bacteria of sterilizing, vaccination target anaerobic bacteria are added in polystyrene sample pipe
The Chinese medicine extract for needing to screen is added afterwards, after closing anaerobic culture for a period of time, adds step 1)Prepared Fe-Co-Ni
Nano-probe, is sufficiently mixed concussion reaction for a period of time, if there is target bacteria growing in sample cell, Fe-Co-Ni nano-probe tables
The antibody in face can be combined with object bacteria first, so that Fe-Co-Ni nano-probes are stayed in a liquid.If not having in sample cell
Object bacteria, then the antibody on Fe-Co-Ni nano-probes surface can gradually adsorb in polystyrene sample pipe surface so that liquid
In there is no Fe-Co-Ni nano-probes.Preceding to have addressed, the nuclear magnetic resonance that micro Fe-Co-Ni nano materials will result in water relaxes
The Henan time declines to a great extent.Using the sterile medium liquid without vaccination target bacterium as blank, during the relaxation of the suspension measured
Between compared to significantly reducing, then illustrate to contain probe in liquid, so as to there is object bacteria in indirect proof sample, the amount and relaxation of probe
The drop-out value of Henan time is proportional, and the amount of object bacteria can be gone out with indirect quantification by the quantitative probe of mark-on.With the presence of object bacteria, then
Illustrate Traditional Chinese medicine bacteriostatic effect it is unobvious, it is on the contrary then illustrate have bacteriostasis.
The major advantage of this method is exactly quick, sensitivity height.Object bacteria can be realized and continuously existed to a certain extent
Line is monitored.Time of even several days 2-3 days relative to anaerobic bacteria culture, magnetic resonance detection only needs a few minutes.The method is not required to
Anaerobic culture box is wanted, can cultivate the sample seal of tube after need to being only inoculated with anaerobic, will be quantitative with syringe during detection
Probe injection can carry out follow-up magnetic resonance detection.Therefore, the screening of extensive Chinese medicine and formula can be made of this method.
The content of the invention
A kind of method that anaerobic bacteria Inhibitors form Chinese Traditional Medicinal Herbs are screened based on Fe-Co-Ni nano-probes.This method, which is that one kind is objective, to be had
The method of object bacteria, can do the quick screening of extensive Chinese medicine and formula, so as to a certain extent in the detection sample of effect
Reduction is directed to certain anaerobic bacteria effective tcm development time significantly.
A kind of method that anaerobic bacteria Inhibitors form Chinese Traditional Medicinal Herbs are screened based on Fe-Co-Ni nano-probes.Using NMR to suitable
The response sensibility of magnetic material, proposes NMR relaxation Parameters variation and Fe-Co-Ni nano-particle paramagnetic immunological probe contents
Correlation metric.This method is used to the detection of object bacteria in sample assess dependent on paramagnetic nano Fe-Co-Ni nano-probes
The fungistatic effect of Chinese medicine preparation., can be to sample using the paramagnetic Fe-Co-Ni nano-probes for being coupled monoclonal antibody specific
Specific anaerobic bacteria in product is detected.Because NMR is very sensitive to Fe-Co-Ni nano-particles, exist micro
Paramagnetic Fe-Co-Ni nano-particles, then the spin-lattice relaxation time of water and/spin-spin relaxation will be remarkably decreased.It is logical
Cross blank control and mark-on and quantitatively detect immunological probe content in sample, the anaerobism gone out so as to indirect quantification in sample
Bacterium clump count.The anaerobism bacterial content detected and probe content linear correlation, degree of fitting are preferable.Finally received with paramagnetic Fe-Co-Ni
Corresponding relation between rice probe and anaerobic bacteria is tie, determines the anaerobic bacteria clump count in sample.So as to determine Chinese medicine indirectly
Whether bacteriostasis is effective.Time of even several days 2-3 days relative to anaerobic bacteria culture, magnetic resonance detection only needs a few minutes.
Therefore, the screening of extensive Chinese medicine and formula can be made of this method.
The present invention is achieved in that step is as follows:
1)Target bacteria antibody is coated with the preparation of paramagnetic nano Fe-Co-Ni nano-probes.
2)The culture medium of the anaerobic bacteria of sterilizing, vaccination target anaerobic bacteria are added in polystyrene sample pipe.Adding needs
The Chinese medicine extract of screening, after culture a period of time, after culture a period of time, adds step 1)Prepared Fe-Co-Ni nanometers
Probe, is sufficiently mixed concussion reaction for a period of time, if there is object bacteria in sample cell, first can be with Fe-Co-Ni nano-probe tables
The antibody binding in face, so that Fe-Co-Ni nano-probes are stayed in a liquid.If not having object bacteria in sample cell, Fe-
The antibody on Co-Ni nano-probes surface can gradually be adsorbed and separated in polystyrene sample pipe surface with liquid.Now, to sample
Pipe carries out the measure of NMR relaxation time.Using the sterile medium liquid without vaccination target bacterium as blank, measure
The relaxation time of suspension, then explanation contained probe, so as to have object bacteria, probe in indirect proof sample compared to significantly reducing
Amount and the decline in relaxation time it is proportional, by mark-on quantitative probe, indirect quantification goes out the amount of object bacteria.
The Fe-Co-Ni nano-probes are the nanoscale Fe-Co-Ni materials with paramagnetic properties, and nanometer particle size is less than
300 nanometers.
The change in final relaxation time of the detection evaluation method based on nuclear magnetic resonance technique of described object bacteria, during relaxation
Between include spin-lattice relaxation time and spin spin relaxation time.
Beneficial effects of the present invention:The present invention, which provides a kind of objectively quick screening, the Chinese medicine of inhibitory action to anaerobic bacteria
The method of formula, it is characterized in that using the corresponding relation between paramagnetic Fe-Co-Ni nano-probes and anaerobic bacteria as tie, determining sample
In anaerobic bacteria clump count.So as to determine whether the bacteriostasis of Chinese medicine is effective indirectly.Relative to anaerobic bacteria culture 2-3 days even
The time of several days, magnetic resonance detection only needs a few minutes.Therefore, the screening of extensive Chinese medicine and formula can be made of this method.
Embodiment
Example 1
Screening is to Propiobacterium(Anaerobic bacteria)There is the Chinese medicine preparation of suppression or therapeutic action.
1)It is prepared by nanometer Fe-Co-Ni immunological probes:
Fe-Co-Ni nano-particles can be commercially(Such as the Chao Wei nano materials company in Shanghai), can also bibliography
With either physically or chemically synthesizing.
Silicon dioxide coated nanometer Fe-Co-Ni:47.5g sodium metasilicate is taken, is dissolved in deionized water in beaker, hydrochloric acid is used
Regulation pH value is 12-13.5.0g nanometer Fes-Co-Ni is taken to be added in this beaker, mechanical agitation (using glass bar) 5min.Will be mixed
Liquid ultrasound 30min is closed, in good time stirring.85 C are warming up to, salt acid for adjusting pH value 6-7, generation precipitation is added dropwise.In Magneto separate
Precipitation is washed with deionized, washs 3-4 times.Then, precipitation is scattered in 250mL methanol.Above procedure in triplicate, is protected
Card silicon is attached on Fe-Co-Ni.
Amino containing silane Fe-Co-Ni nano materials:Obtained silicon dioxide coated nanometer Fe-Co-Ni is added to
In 25mL methanol, 1mLH is used2O and methanol dilution are to 150mL.Then the mixing of 150mL glycerine is added.Ultrasonic 30min, has been transferred to
In the 500mL three-necked flasks of agitating device.Add 10mL amino silicane coupling agents(AEAPS), quickly stirred under 80-90 C
After 3h, product is transferred out of.Product is washed with deionized 3 times, and methanol washs 2 times (using Buchner funnel suction filtration).Vacuum drying.Need
It should be noted that suction filtration is due to there is glycerine, so slow, supernatant liquid can be sucked with suction pipe in good time after a period of time by taking out, and be taken out
Filtration journey about needs 6-8h.Obtained Aminosilylation Fe-Co-Ni nano materials are finally dried in vacuo 12h.
Antibody modification:Weigh a certain amount of amido modified Fe-Co-Ni nano-particles, add 2 times of quality EDC and
NHS, adds 0.01M each 1mL of PBS.It is placed on blending instrument, 15 turns of rotating speed, reacts 45min.)By soak time to sample enter
Row 10000r/min is centrifuged, time 5min, and the PBS for then adding 0.01M carries out washing centrifugation, is repeated 3 times.By what is centrifuged
Sample respectively adds excessive Propiobacterium antibody, and 1h is coupled on blending instrument.The 10%BSA confining liquids added after the completion of coupling
45min.After closing terminates, rotating speed 8000r/min centrifuges 5min, is centrifuged, is repeated 3 times with 0.01M PBS, then will
Unnecessary antibody, BSA are washed away, and are eventually adding PBS and are resuspended.The Fe-Co-Ni nano-particles of the resistance modification of preparation are to exempt from
Epidemic disease probe, be stored in 4 DEG C it is stand-by.
2)The culture medium sterilized in right amount is each added in a collection of polystyrene sample pipe, acne bar is inoculated with oxygen free condition
Bacterium, is separately added into after the Chinese medicine extract sealing for needing to screen, after culture a period of time, adds step 1)Prepared Fe-Co-
Ni nano-probes, are sufficiently mixed concussion reaction, if there is object bacteria in sample cell, first can be with Fe-Co-Ni nano-probes surface
Antibody binding so that Fe-Co-Ni nano-probes are stayed in a liquid;If not having object bacteria in sample cell, Fe-Co-
The antibody on Ni nano-probes surface can be adsorbed gradually in polystyrene sample pipe surface.After reaction 1 hour, core is carried out to sample cell
The measure in magnetic resonance relaxation time(Shanghai knob steps NMR20 NMRs).With the sterile culture medium without vaccination target bacterium
Liquid is blank, and the relaxation time spin-lattice relaxation time of the suspension measured has been compared aobvious with spin spin relaxation time
Reduction is write, then explanation contains probe, illustrates there is object bacteria in sample cell, so that the bacteriostasis of side light Chinese medicine is not obvious,
It is on the contrary then anti-.The amount of probe and the decline of spin-lattice relaxation time and spin spin relaxation time are proportional, pass through mark-on
Quantitative probe and indirect quantification go out the amount of object bacteria.Illustrate that the Chinese medicine added does not have inhibitory action with the presence of object bacteria.It is on the contrary then
Instead.
Embodiment
Example 2
Screening is to clostridium(Anaerobic bacteria)There is the Chinese medicine preparation of suppression or therapeutic action.
1)It is prepared by nanometer Fe-Co-Ni immunological probes:
Fe-Co-Ni nano-particles can be commercially(Such as the Chao Wei nano materials company in Shanghai), can also bibliography
With physics and it is chemically synthesized.
Silicon dioxide coated nanometer Fe-Co-Ni:47.5g sodium metasilicate is taken, is dissolved in deionized water in beaker, hydrochloric acid is used
Regulation pH value is 12-13.5.0g nanometer Fes-Co-Ni is taken to be added in this beaker, mechanical agitation (using glass bar) 5min.Will be mixed
Liquid ultrasound 30min is closed, in good time stirring.85 C are warming up to, salt acid for adjusting pH value 6-7, generation precipitation is added dropwise.In Magneto separate
Precipitation is washed with deionized, washs 3-4 times.Then, precipitation is scattered in 250mL methanol.Above procedure in triplicate, is protected
Card silicon is attached on Fe-Co-Ni.
Amino containing silane Fe-Co-Ni nano materials:Obtained silicon dioxide coated nanometer Fe-Co-Ni is added to
In 25mL methanol, 1mLH is used2O and methanol dilution are to 150mL.Then the mixing of 150mL glycerine is added.Ultrasonic 30min, has been transferred to
In the 500mL three-necked flasks of agitating device.Add 10mL amino silicane coupling agents(AEAPS), quickly stirred under 80-90 C
After 3h, product is transferred out of.Product is washed with deionized 3 times, and methanol washs 2 times (using Buchner funnel suction filtration).Vacuum drying.Need
It should be noted that suction filtration is due to there is glycerine, so slow, supernatant liquid can be sucked with suction pipe in good time after a period of time by taking out, and be taken out
Filtration journey about needs 6-8h.Obtained Aminosilylation Fe-Co-Ni nano materials are finally dried in vacuo 12h.
Antibody modification:Weigh a certain amount of amido modified Fe-Co-Ni nano-particles, add 2 times of quality EDC and
NHS, adds 0.01M each 1mL of PBS.It is placed on blending instrument, 15 turns of rotating speed, reacts 45min.)By soak time to sample enter
Row 10000r/min is centrifuged, time 5min, and the PBS for then adding 0.01M carries out washing centrifugation, is repeated 3 times.By what is centrifuged
Sample respectively adds excessive clostridium antibody, and 1h is coupled on blending instrument.The 10%BSA confining liquids added after the completion of coupling
45min.After closing terminates, rotating speed 8000r/min centrifuges 5min, is centrifuged, is repeated 3 times with 0.01M PBS, then will
Unnecessary antibody, BSA are washed away, and are eventually adding PBS and are resuspended.The Fe-Co-Ni nano-particles of the resistance modification of preparation are to exempt from
Epidemic disease probe, be stored in 4 DEG C it is stand-by.
2)The culture medium sterilized in right amount is each added in a collection of polystyrene sample pipe, fusiform bud is inoculated with oxygen free condition
Spore bacillus, is separately added into after the Chinese medicine extract sealing for needing to screen, after culture a period of time, adds step 1)Prepared
Fe-Co-Ni nano-probes, are sufficiently mixed concussion reaction, if there is object bacteria in sample cell, first can be with Fe-Co-Ni nanometers of spies
The antibody binding of wire surface, so that Fe-Co-Ni nano-probes are stayed in a liquid.If not there is object bacteria in sample cell,
The antibody on Fe-Co-Ni nano-probes surface can be adsorbed gradually in polystyrene sample pipe surface.After reaction 1 hour, to sample cell
Carry out the measure of NMR relaxation time(Shanghai knob steps NMR20 NMRs).With sterile without vaccination target bacterium
Medium liquid is blank, and the spin-lattice relaxation time of the suspension measured has been compared significantly with spin spin relaxation time
Reduction, then illustrate to contain probe, illustrate there is object bacteria in sample cell, so that the bacteriostasis of side light Chinese medicine is not obvious, instead
It is then anti-.The amount of probe and the decline of spin-lattice relaxation time and spin spin relaxation time are proportional, fixed by mark-on
Amount probe and indirect quantification goes out the amount of object bacteria.Illustrate that the Chinese medicine added does not have inhibitory action with the presence of object bacteria.It is on the contrary then anti-.
Claims (3)
1. a kind of method that anaerobic bacteria Inhibitors form Chinese Traditional Medicinal Herbs are screened based on Fe-Co-Ni nano-probes, its characterization step is as follows:
1)Target bacteria antibody is coated with the preparation of paramagnetic Fe-Co-Ni nano-probes;
2)The culture medium of the anaerobic bacteria of sterilizing is added in polystyrene sample pipe, vaccination target anaerobic bacteria, addition needs screening
Chinese medicine preparation extract solution, after closed culture a period of time, step 1 is quantitatively adding with syringe)Prepared Fe-Co-Ni receives
Rice probe, is sufficiently mixed concussion reaction for a period of time, if there is object bacteria in sample cell, Fe-Co-Ni nano-probes surface it is anti-
Body can be combined with object bacteria first, so that Fe-Co-Ni nano-probes are stayed in a liquid;If not there is target in sample cell
Bacterium, then the antibody on Fe-Co-Ni nano-probes surface can gradually adsorb and leave nutrient solution in polystyrene sample pipe surface;This
When, the measure of NMR relaxation time is carried out to sample cell;Using the sterile medium liquid without vaccination target bacterium as sky
In vain, the relaxation time of the suspension measured, then explanation contained probe, so as to have mesh in indirect proof sample compared to significantly reducing
Bacterium is marked, the amount of probe and the decline in relaxation time are proportional, indirect quantification goes out the amount of object bacteria by mark-on quantitative probe;Sample
There is no object bacteria to illustrate that the traditional Chinese medicine ingredients added have a fungistatic effect in QC, it is on the contrary then anti-.
2. the method according to claim 1 that anaerobic bacteria Inhibitors form Chinese Traditional Medicinal Herbs are screened based on Fe-Co-Ni nano-probes, it is special
It is that the nanometer Fe-Co-Ni nano-probes are the nanometer Fe-Co-Ni alloy materials with paramagnetic properties to levy, and nanometer particle size is less than
300 nanometers.
3. the method according to claim 1 that anaerobic bacteria Inhibitors form Chinese Traditional Medicinal Herbs are screened based on Fe-Co-Ni nano-probes, it is special
Levy the change in final relaxation time of the detection evaluation method based on nuclear magnetic resonance technique for being described object bacteria.
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Citations (3)
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JPS61268187A (en) * | 1985-05-22 | 1986-11-27 | Kitasato Inst:The | Novel antibiotic substance sk-1071 and production thereof |
EP0280894A1 (en) * | 1987-02-03 | 1988-09-07 | Mitsubishi Kasei Corporation | Novel antibiotic vermisporin, process for the production thereof and pharmaceutical composition comprising it as an active antibacterial agent |
CN1808106A (en) * | 2005-01-21 | 2006-07-26 | 中国科学院上海药物研究所 | Method for screening acetylcholine esterase inhibitor by nuclear magnetic resonance |
-
2017
- 2017-04-10 CN CN201710228480.0A patent/CN107144589A/en not_active Withdrawn
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS61268187A (en) * | 1985-05-22 | 1986-11-27 | Kitasato Inst:The | Novel antibiotic substance sk-1071 and production thereof |
EP0280894A1 (en) * | 1987-02-03 | 1988-09-07 | Mitsubishi Kasei Corporation | Novel antibiotic vermisporin, process for the production thereof and pharmaceutical composition comprising it as an active antibacterial agent |
CN1808106A (en) * | 2005-01-21 | 2006-07-26 | 中国科学院上海药物研究所 | Method for screening acetylcholine esterase inhibitor by nuclear magnetic resonance |
Non-Patent Citations (1)
Title |
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申静 等: "基于NMR纳米探针的生物传感器用于快速检测沙门氏菌", 《食品工业科技》 * |
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