CN108101793A - A kind of compound and its competition fluorescence detection method applied to adamantane aminated compounds - Google Patents
A kind of compound and its competition fluorescence detection method applied to adamantane aminated compounds Download PDFInfo
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Abstract
A kind of competition fluorescence detection method the invention discloses compound and its applied to adamantane aminated compounds.The present invention provides a kind of new compound as fluorescence probe, and fluorescence probe used prepares that required equipment is simple, and operating process simplicity, all commercialization has been easy to get raw material sources.The fluorescence probe property that the compound is combined prepared detection adamantane aminated compounds with cucurbit [7] urea is very stable, and purity is also very high.And fluorescence probe provided by the invention is when for the fluorescence detection method of adamantane aminated compounds, compared with the basic skills of previously used detection adamantane aminated compounds, have the advantages that quick, high sensitivity, strong interference immunity, testing cost are low etc., this method can be down to 9 × 10 to the minimum detection limit of amantadine‑5μ g/mL, the minimal detectable concentration that can reach in the method for being the detection amantadine having been reported that at present.
Description
Technical field
The present invention relates to a kind of noval chemical compound, the compound can be used as fluorescence probe, applied to adamantane amine
The competitive coordination fluorescence detection method of compound.
Background technology
Adamantane aminated compounds was once used as antiviral drugs and anti-shudder by U.S. Food and Drug Administration's approval
Paralytic uses.From 2005, Chinese poultry resource peasant household protected birds anti-avian influenza using adamantane aminated compounds.This
Abuse of the class drug on livestock and poultry results in animal food drug residue, animal virus, animal body and generates immunosupress
And the problems such as drug resistance, it and is also possible to that virus is caused to morph, influence animal epidemic control and people's virus drugs has
Effect property.Therefore from 2005 regulatory agencies of Nian Qi Chinese Government it has been forbidden to be used as veterinary drug.But aquaculture is engaged in part
The food security and legal consciousness faint of personnel, China is currently without the substitute products of antiviral drugs, while adamantane in addition
Aminated compounds is cheap, the phenomenon that causing the antiviral drugs such as this Misuse amantadine still happen occasionally [in
State's veterinary drug magazine, 2013,47 (10), 54-61].And the animal products detection of veterinary drugs in food of the second half year in 2016 of Ministry of Agriculture's circular
It turns out that the residual of amantadine is still checked in animal products.
The method of residual quantity currently used for detecting amantadine mainly includes two kinds：One kind is exempted from using competitiveness enzyme-linked
Epidemic disease reaction principle carries out the residual of tissue and the firm alkanamine of other Gold Samples quantitative detection, with U.S.'s kernel amantadines
Testing cassete is representative；Another kind is ultra high efficiency liquid phase-tandem mass spectrum method.Wherein the method for LC-MS can not only detect gold
Firm alkane amine drug also is adapted for residual quantity [the Chinese patent CN104155398B of detection other drugs；State of the People's Republic of China (PRC)
The bulletin-6-2016 of standard agricultural portion of family 2483].But both approaches there are detection time is long and the higher grade of cost not
Foot part.
Cucurbituril (Cucurbit [n] uril, n=5,6,7,8,10) is a kind of new supermolecule main block, by methylene
The macrocyclic compound with hydrophobic cavity that the different number of glycoluril unit of bridging is formed.Cucurbituril main body can selectively with
Different types of guest molecule, especially cationic object combine to form inclusion compound, change guest molecule to a certain extent
Physicochemical properties.This property causes Cucurbituril as host molecule in organic synthesis, molecular recognition, Journal of Molecular Catalysis, load
The directions such as medicine have obtained extensive research.
In terms of drug test, fluorescence probe system and drug molecule that Cucurbituril and fluorescent probe molecule combine to form it
Between interaction, form the super-sensitive fluorescence spectrum detection method for these drug molecules.By this new
Fluorescence probe system and non-blooming drug molecule between competitive interaction, establish unstressed configuration pharmaceutical analysis side
Method, this has great significance to the detection research of unstressed configuration drug molecule.
Fluoroscopic examination is a kind of natural luminescence-producing reaction, and sensitivity is high, and selectivity is good, and the range of linearity is wide, and 1975 first
It is applied in food industry, was applied in 1985 in cosmetic formulation art.Fluoroscopic examination can be divided into catalytic fluorescence method
With two class of fluorescence quemching method.
Supramolecular system detection amantadine content of professor Du Liming of Shanxi Normal University in 2012 based on Cucurbituril
Method (Wang, G.-Q.；Qin,Y.-F.；Du,L.-M.；Li.J.-F.；Chang,Y.-X.；Wu,
H.Spectrochim.Acta A,2012,98,275-218).It is tied in this method with this fluorescence molecule of coptisine and CB [7]
It closes, forms new fluorescence probe system, be at war with coordination with the amantadine molecule in sample to be tested, pass through amantadine general
Fluorescence probe system can reach detection Gold Samples there are one this effect of fluorescent quenching after the cavity of coptisine extrusion CB [7]
The purpose of firm alkanamine content.But the detection method is disadvantageous in that, the binding constant of coptisine and amantadine is very
It is low, only 104M-1.And the binding ability of the other drugs impurity and Cucurbituril in real sample to be tested, it can also reach very
Extremely it is more than such a order of magnitude, therefore the cavity of coptisine extrusion CB [7] can be caused fluorescence intensity by these impurity of the drug
Variation.Final testing result can thus be interfered, the measure of amantadine content is made to generate certain error.
Therefore, designing a kind of detection method of the low amantadine of quick, sensitive, strong interference immunity, testing cost is
Reasonably necessary and urgent.
The content of the invention
The object of the present invention is to provide a kind of fluorescence detection method of amantadine, the fluorescence probe used in method is one
Kind noval chemical compound, its preparation method is simple, and property is stablized, and the accuracy of detection, accuracy are high.
The technical solution adopted by the present invention is as follows：
One kind such as formula (I) compound represented：
In formula (I), R1For one of group as shown in formula (II)-formula (IV)：
In formula (I), R2For one of fluorophor as shown in formula (V)-formula (IX)：
The compound is preferably as shown in formula (A)：
The present invention also provides described such as the preparation method of formula (I) compound represented, the method includes following step
Suddenly：A. by containing R1The amine of group and R containing fluorophor2Halogen compounds remove hydrogen halides in alkaline conditions, obtain ammonia
Base target compound；B. HCl gases are passed through to amino solution title compound, obtain the hydrochloride of target compound.
More specifically, the preparation method of the present invention such as formula (X) compound represented comprises the following steps：
A) dissolving in tetrahydrofuran (THF) by the compound 2 (p dimethylamine) of 2.0 equivalents, at room temperature, adds in enough
Triethylamine THF solution, stir one hour；
B) acquired solution is placed in oil bath pan the 70 DEG C of reflux that heat up in step a, after reflux starts, is delayed with constant pressure funnel
The tetrahydrofuran solution (time for adding 30 minutes) of the compound 1 (9- chloromethyls anthracene) of slow 1.0 equivalent of dropwise addition；
C) after being added dropwise to complete, reaction mixture continue reflux 3 it is small when；
D) after mixture is cooled to room temperature, rotary evaporation removes solvent, and residue is dissolved in dichloromethane；Dichloromethane is organic
After mutually washing 3 times, Na is used2SO4It is dry；
E) crude compound carries out column chromatography for separation purification, and eluant, eluent is dichloromethane and methanol volume ratio 10:1 mixing
Liquid, collects the eluent containing target compound, and concentrate drying obtains sterling compound 3；
F) compound 3 is dissolved in acetonitrile, HCl is passed through into solution, can be observed there is precipitation to generate.Precipitating filtration drying is
Obtain compound A；
The present invention such as formula (I) compound represented can be used as fluorescence probe, the fluoroscopic examination applied to amantadine.It is described
The method of fluoroscopic examination of amantadine be：At 25 DEG C of constant temperature, by the fluorescent probe molecule shown in formula (I) in advance and cucurbit
[7] urea combines to form complex, and solution is placed in 25 DEG C of Fluorescence Spectrometer thermostats, adds known to a series of amantadine concentration
Sample, after being added according to amantadine at caused 417nm fluorescence intensity changing value, it is strong that probe molecule fluorescence can be made
Spend the standard curve and linear fit equation with the variation of amantadine concentration；When measuring amantadine concentration in sample to be tested, only
The difference of fluorescence intensity after addition sample to be tested need to be brought into corresponding linear fit equation, you can draw in sample
The concentration of amantadine.
The principle schematic of present invention detection amantadine is as shown in Figure 1.Its principle is：
It is combined in advance with cucurbit [7] urea by fluorescent probe molecule, adds the amantadine of known sample concentration.Buddha's warrior attendant
Fluorescent probe molecule is displaced the cavity of cucurbit [7] urea by alkanamine because stronger with the binding ability of cucurbit [7] urea.And fluorescence
Probe molecule can trigger the variation of strong fluorescence signal because of residing environmental change.This variation and the concentration of amantadine are deposited
In certain linear relationship.The variation of fluorescence signal according to caused by a series of amantadine of known sample concentration of addition,
The standard curve that probe molecule fluorescence intensity changes with amantadine concentration can be made.Measure amantadine concentration in sample to be tested
When, the fluorescence intensity after addition sample to be tested need to only be compared with standard curve, you can draw the standard of amantadine in sample
True concentration.
Further, the fluorescent probe molecule in the method for the fluoroscopic examination of the amantadine shown in formula (I) and cucurbit
[7] concentration of urea is equivalent, and the solvent of cucurbit [7] urea and fluorescent probe molecule is the sodium acetate buffer of pH=4.74.
When the compound is shown in formula (A), the method for the fluoroscopic examination of the amantadine is according to following steps
It carries out：25 degrees Celsius of constant temperature,
A) solution of the compound A of debita spissitudo is configured, solvent is the sodium acetate buffer of pH=4.74；
B) solution of cucurbit [7] urea of high concentration is configured, solvent is the sodium acetate buffer of pH=4.74, with compound
A presses 1:The amount of 1 metering ratio is added in the solution of compound A, and solution is placed in 25 DEG C of Fluorescence Spectrometer thermostats；
C) the amantadine solution of known concentration is added in, records the changing value of fluorescence intensity at 417nm；
D) being drawn according to above-mentioned fluorescence intensity with the variation of amantadine concentration, (abscissa is amantadine concentration, indulges and sits
It is designated as the changing value of dye molecule fluorescence intensity), and linear fit obtains fit equation；
E) the amantadine sample of unknown concentration is added to compound A in the inclusion complex in solution of cucurbit [7] urea, recording
The changing value of fluorescence intensity after addition, this changing value, which is brought into above-mentioned fit equation, can calculate amantadine sample to be measured
Concentration.
Compared with prior art, the present invention its advantage is embodied in：
(1) provide a kind of new compound as fluorescence probe, fluorescence probe used to prepare required equipment simple,
Operating process is easy, and all commercialization has been easy to get raw material sources.
(2) compared with the method for previously used detection amantadine, the present invention has quick, high sensitivity, anti-interference
Advantages, this method such as property is strong, testing cost is low can be down to 9 × 10 to the minimum detection limit of amantadine-5μ g/mL, be at present
(minimal detectable concentration reported before this is the minimal detectable concentration that can reach in the method for the detection amantadine reported
1.18×10-4μg/mL.Referring to document Jalali, F.；Maghooli,R.,Analytical Sciences 2009,25(10),
1227-1230)。
Description of the drawings
Fig. 1 is the principle schematic of detection amantadine；
Fig. 2 is to add in the nuclear-magnetism figure that different equivalent cucurbit [7] ureas carry out nuclear-magnetism titration experiments to fluorescence probe A；
The method of nuclear-magnetism titration determines that fluorescence probe A and cucurbit [7] urea can form 1:1 complex；
A is free fluorescence probe nuclear-magnetism figure；For b to add in 0.5 equivalent cucurbit [7] urea, c is 1 equivalent cucurbit [7] of addition
Urea；
Fig. 3 is to add in the change in fluorescence figure that different equivalent cucurbit [7] ureas carry out fluorescence titration experiment to fluorescence probe A；
Fig. 4 is to add in different equivalent amantadines to the change in fluorescence figure in fluorescence probe A and cucurbit [7] urea complex；
Fig. 5 is amantadine concentration and the standard curve of fluorescence probe variation；
a：Amantadine concentration and the standard curve ([probe]=[cucurbit [7] urea]=2.0 μM) of fluorescence probe variation
b：Amantadine concentration and the standard curve ([probe]=[cucurbit [7] urea]=0.2 μM) of fluorescence probe variation.
Specific embodiment
By following detailed description combination attached drawing it will be further appreciated that the features and advantages of the invention.The implementation provided
Example is only explanation to the method for the present invention, remaining content without limiting the invention in any way announcement.
【Embodiment 1】Prepare fluorescence probe A
A) dissolving in tetrahydrofuran (THF) by the compound 2 (p dimethylamine) of 3.5mmol (480mg), at room temperature,
The THF solution of enough triethylamines is added in, is stirred one hour；
B) acquired solution is placed in temperature rising reflux in oil bath pan in step a, slow with constant pressure funnel after reflux starts
The tetrahydrofuran solution (time for adding 30 minutes) of the compound 1 (9- chloromethyls anthracene) of 1.7mmol (400mg) is added dropwise；
C) after being added dropwise to complete, reaction mixture continue reflux 3 it is small when；
D) after mixture is cooled to room temperature, rotary evaporation removes solvent, and residue is dissolved in dichloromethane.Dichloromethane is organic
After mutually washing 3 times, Na is used2SO4It is dry；
E) crude compound carries out column chromatography for separation purification, and eluant, eluent is dichloromethane and methanol volume ratio 10:1 mixing
R is collected in liquid, TLC trackingfIt is worth the eluent for 0.35, the eluent collected obtains 480mg sterlings through solvent is removed under reduced pressure
Compound 3, yield 54%；
F) compound 3 is dissolved in acetonitrile, HCl is passed through into solution, can be observed there is precipitation to generate.Precipitating filtration drying is
Obtain compound A.
Compound A nuclear magnetic resonance results：
1H NMR(600MHz,D2O)
δ4.12(s,2H,CH2),4.38(s,2H,CH2),5.14(s,2H,CH2),7.42(m,2H,CH),7.44(d,2H,
CH),7.43(t,2H,CH),7.52(t,2H,CH),7.92(d,2H,CH),8.05(d,2H,CH),8.60(s,1H,CH).
13C NMR(150MHz,D2O)
δ c134.18 (CH), 130.94 (C), 130.84 (C), 130.27 (CH), 130.03 (CH), 129.67 (C),
129.46 (CH), 129.18 (CH), 127.35 (CH), 125.27 (CH), 121.78 (CH), 119.78 (CH), 50.15 (CH2),
42.59(CH2), 40.65 (CH2)。
The fluorescence probe with different binding sites (R1) and different fluorophors (R2) can be obtained by this similar approach.
【Embodiment 2】The method of nuclear-magnetism titration determines that fluorescence probe A and cucurbit [7] urea can form complex
As shown in Fig. 2, the concentration of fluorescence probe is 1.0mM (nuclear-magnetism titration experiments are carried out in heavy water).A figures are free
Fluorescence probe nuclear-magnetism figure, b figures are to add in 0.5 equivalent cucurbit [7] urea, and c figures are to add in 1 equivalent cucurbit [7] urea.It can be in b figures
Fluorescence probe nuclear magnetic signal peak that is free and combining is monitored simultaneously, illustrates fluorescence probe and cucurbit [7] urea in the nuclear-magnetism time
Scale is a compact slow exchange.The nuclear magnetic signal peak of R1 groups is moved to High-Field on probe molecule, illustrates R1 bases
Group enters the cavity of cucurbit [7] urea；The nuclear magnetic signal peak of R2 fluorophors is moved to low field, illustrates that R2 groups are in cucurbit
[7] outside urea port.Without there is free Subjective and Objective nuclear magnetic signal peak in c figures, illustrate that fluorescence probe and cucurbit [7] urea form
1:1 complex.And cucurbit [7] urea of more equivalents is added in, the nuclear magnetic signal peak of probe no longer changes, and illustrates that R2 groups cannot be into
Enter the cavity of cucurbit [7] urea, fluorescence probe and cucurbit [7] urea only form 1:1 complex.
【Embodiment 3】The method of fluorescence titration determines that probe A and cucurbit [7] urea can form complex
As shown in figure 3, the concentration of fluorescence probe is 2.0 μM of (vinegar that the solvent of all fluorescence titration experiments is pH=4.74
Sour sodium buffer solution).After cucurbit [7] urea is added in, fluorescence signal (excitation wavelength 366nm, the launch wavelength of monitoring of probe
For 417nm) it is varied widely；Add in 1 equivalent cucurbit [7] urea after, continuously add cucurbit [7] urea can not cause it is glimmering
The significant changes of light.Illustrate that probe can form very strong 1 with cucurbit [7] urea:1 complex.
【Embodiment 4】Determine that amantadine competitive coordination triggers fluorescence probe change in fluorescence
As shown in figure 4, the concentration of fluorescence probe and cucurbit [7] urea is all 2.0 μM.With the addition of amantadine, fluorescence
Probe is displaced the cavity of cucurbit [7] urea, and fluorescence intensity constantly reduces.After the amantadine of addition is an equivalent,
The significant changes of fluorescence can not be caused by continuously adding amantadine.Illustrate that amantadine will be glimmering in cucurbit [7] urea cavity
Light probe displacement is complete.Show amantadine with the bond strength of cucurbit [7] urea much larger than fluorescence probe and the knot of cucurbit [7] urea
Close intensity.Show that this system is consistent with expection simultaneously, the concentration mensuration available for amantadine compound.
【Embodiment 5】Draw standard curve
By changing probe and cucurbit [7] urea complex concentration, a series of amantadine of known sample concentration is added in, is surveyed
Determine the variation of fluorescence signal.According to amantadine concentration and corresponding fluorescence intensity change, it is strong that fitting obtains probe molecule fluorescence
Spend the standard curve and linear fit equation with the variation of amantadine concentration.In Fig. 5 a, the concentration of probe and cucurbit [7] urea is all
2.0 μM, detection range of amantadine is in the μ g/mL of 0.0375 μ g/mL~0.375 under the conditions of this.In Fig. 5 b, probe and cucurbit
[7] concentration of urea is all 0.2 μM, and detection range of amantadine is in the μ g/mL of 0.000188 μ g/mL~0.0375 under the conditions of this.
The lowest detection that can be reached by this detection method is limited to 9 × 10-5μg/mL。
【Embodiment 6】Determine the accuracy of linear fit equation and the anti-interference of Subjective and Objective fluorescence probe system
Four kinds of veterinary drugs (Ofloxacin, Ribavirin, fortimicin, Florfenicol) are mixed into the known concentration of configuration
In amantadine solution, concentration is 100 times of amantadine, and fluorescence probe system is investigated in authentic sample for simulating
The anti-interference of other existing veterinary drugs.This testing sample solution is added in into probe in the complex solution of cucurbit [7] urea, leading to
The variation (excitation wavelength 366nm) of fluorescence intensity at monitoring 417nm is crossed, fluorescence intensity difference is brought into such as embodiment 5
In the corresponding linear fit equation that method determines, the concentration of the amantadine in sample to be tested can be obtained.After testing, it is all
Linear fit equation can obtain accurate amantadine concentration, and error is within 5%.Show such veterinary drug and cucurbit [7]
The bond strength of urea is far weaker than fluorescence probe, so not made a significant impact on testing result.
Claims (7)
1. one kind is such as formula (I) compound represented：
In formula (I), R1For one of group as shown in formula (II)-formula (IV)：
In formula (I), R2For one of fluorophor as shown in formula (V)-formula (IX)：
2. compound as described in claim 1, which is characterized in that shown in its structural formula such as formula (A)：
3. as described in claim 1 such as the preparation method of formula (I) compound represented, it is characterised in that the method includes
Following steps：A. by containing R1The amine of group and R containing fluorophor2Halogen compounds remove hydrogen halides in alkaline conditions,
Obtain amino target compound；B. HCl gases are passed through to amino solution title compound, obtain the hydrochloride of target compound.
4. as claimed in claim 3 such as the preparation method of formula (I) compound represented, which is characterized in that the method bag
Include following steps：
A) dissolving in tetrahydrofuran (THF) by the compound 2 (p dimethylamine) of 2.0 equivalents, at room temperature, adds in enough three
The THF solution of ethamine stirs one hour；
B) acquired solution is placed in oil bath pan the 70 DEG C of reflux that heat up in step a, slow with constant pressure funnel after reflux starts
The tetrahydrofuran solution (time for adding 30 minutes) of the compound 1 (9- chloromethyls anthracene) of 1.0 equivalents is added dropwise；
C) after being added dropwise to complete, reaction mixture continue reflux 3 it is small when；
D) after mixture is cooled to room temperature, rotary evaporation removes solvent, and residue is dissolved in dichloromethane；Dichloromethane organic phase water
After washing 3 times, Na is used2SO4It is dry；
E) crude compound carries out column chromatography for separation purification, and eluant, eluent is dichloromethane and methanol volume ratio 10:1 mixed liquor,
The eluent containing target compound is collected, concentrate drying obtains sterling compound 3；
F) compound 3 is dissolved in acetonitrile, HCl is passed through into solution, can be observed there is precipitation to generate.Precipitation filtration drying obtains
Compound A；
5. as described in claim 1 such as the application of formula (I) compound represented, which is characterized in that the compound can conduct
Fluorescence probe, applied to the fluoroscopic examination of amantadine, the method for the fluoroscopic examination of the amantadine is：25 DEG C of constant temperature
Under, complex is combined to form with cucurbit [7] urea by the fluorescent probe molecule shown in formula (I) in advance, solution is placed in 25 DEG C of fluorescence
Spectrometer thermostat adds a series of sample known to amantadine concentration, caused by after being added according to amantadine
The changing value of fluorescence intensity at 417nm, can make standard curve that probe molecule fluorescence intensity changes with amantadine concentration and
Linear fit equation；It, only need to be by the difference of the fluorescence intensity after addition sample to be tested when measuring amantadine concentration in sample to be tested
Value is brought into corresponding linear fit equation, you can draws the concentration of amantadine in sample.
6. application as claimed in claim 5, which is characterized in that be formula in the method for the fluoroscopic examination of the amantadine
(I) concentration of fluorescent probe molecule and cucurbit [7] urea shown in is the solvent of equivalent, cucurbit [7] urea and fluorescent probe molecule
For the sodium acetate buffer of pH=4.74.
7. application as claimed in claim 6, which is characterized in that the compound is shown in the formula (A) described in claim 2
When, the method for the fluoroscopic examination of the amantadine follows the steps below：
A) solution of the compound A of debita spissitudo is configured, solvent is the sodium acetate buffer of pH=4.74；
B) solution of cucurbit [7] urea of high concentration is configured, solvent is the sodium acetate buffer of pH=4.74, is pressed with compound A
1:The amount of 1 metering ratio is added in the solution of compound A, and solution is placed in 25 DEG C of Fluorescence Spectrometer thermostats；
C) the amantadine solution of known concentration is added in, records the changing value of fluorescence intensity at 417nm；
D) being drawn according to above-mentioned fluorescence intensity with the variation of amantadine concentration, (abscissa is amantadine concentration, and ordinate is
The changing value of dye molecule fluorescence intensity), and linear fit obtains fit equation；
E) the amantadine sample of unknown concentration is added to compound A and in the inclusion complex in solution of cucurbit [7] urea, record adds in
The changing value of fluorescence intensity afterwards, this changing value, which is brought into, can calculate the dense of amantadine sample to be measured in above-mentioned fit equation
Degree.
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| CN112316158A (en) * | 2020-11-19 | 2021-02-05 | 四川大学 | Method for closing antibacterial agent activity in collagen solution by using supermolecule encapsulating agent |
| CN112362624A (en) * | 2020-11-10 | 2021-02-12 | 云南中烟工业有限责任公司 | Supermolecule fluorescence analysis method for detecting alcohol perfume compounds |
| CN113075179A (en) * | 2021-03-24 | 2021-07-06 | 中国药科大学 | Method for detecting ketamine by using supramolecular fluorescent probe |
| CN113424049A (en) * | 2019-02-12 | 2021-09-21 | 艾伦塔斯欧洲有限公司 | Self-diagnostic resin and associated fibre composite material |
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| US7718128B2 (en) * | 2005-10-20 | 2010-05-18 | Postech Foundation | Application using non-covalent bond between a cucurbituril derivative and a ligand |
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| US20050026068A1 (en) * | 2001-11-01 | 2005-02-03 | Evangelos Gogolides | Polycarbocyclic derivatives for modification of resist, optical and etch resistance properties |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113424049A (en) * | 2019-02-12 | 2021-09-21 | 艾伦塔斯欧洲有限公司 | Self-diagnostic resin and associated fibre composite material |
| CN112362624A (en) * | 2020-11-10 | 2021-02-12 | 云南中烟工业有限责任公司 | Supermolecule fluorescence analysis method for detecting alcohol perfume compounds |
| CN112316158A (en) * | 2020-11-19 | 2021-02-05 | 四川大学 | Method for closing antibacterial agent activity in collagen solution by using supermolecule encapsulating agent |
| CN112316158B (en) * | 2020-11-19 | 2021-09-21 | 四川大学 | Method for closing antibacterial agent activity in collagen solution by using supermolecule encapsulating agent |
| CN113075179A (en) * | 2021-03-24 | 2021-07-06 | 中国药科大学 | Method for detecting ketamine by using supramolecular fluorescent probe |
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