CN106588911A - Novel thiazole compound XQH-3-6 resisting streptococcus mutans and application of compound - Google Patents
Novel thiazole compound XQH-3-6 resisting streptococcus mutans and application of compound Download PDFInfo
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Abstract
The invention discloses a novel thiazole compound capable of inhibiting streptococcus mutans. The compound number is XQH-3-6, the molecular formula is C16H16ClN5O4S, the molecular weight is 409.85, and the Chinese name is N1-(3-chlorphenyl-N4-(5-nitrothiazole-2-yl))piperidine-1,4-dicarboxamide. Experiments show that the compound presents the good antibacterial activity and fungicidal activity on type strains and clinical strains of the streptococcus mutans in a floating state. Meanwhile, when the final concentration of the compound XQH-3-6 in a culture medium reaches 4 mg/L, the inhibition ratio of streptococcus mutans biological membrane reaches 97% or above. The compound is small in molecular weight and simple in structure, inhibition experiments prove that the compound has the advantages of being high in inhibition, good in killing effect and the like, growth of main pathogen-streptococcus mutans buoyant cells of caries and formation of a biological membrane can be significantly inhibited, the potential of preventing the caries is achieved, and the compound can serve as a novel targeted candidate drug for preventing the caries.
Description
Technical field
The present invention relates to a kind of thiazole compound, more particularly to a kind of novel thiazole class compound of Streptococcus mutans
XQH-3-6 and its application.The compound can suppress the growth of oral cavity periodontal antibacterial, can be used to prevent and treat dental caries, belong to oral cavity
Diseases prevention and treatment field of medicine preparing technology.
Background technology
Dental caries (Dental caries) are commonly called as decayed tooth, are a kind of common chronic diseases in oral cavity.Dental caries chronic progression enters
And irreversible damage is caused to dental hard tissue, extensively, sickness rate is high for its distribution, not only brings pain to individual,
Cause huge medical resource to waste, it has also become threaten the global problem of Human Oral Cavity health, World Health Organization (WHO) (WHO)
Be classified as one of three big noninfectiouss (cardiovascular disease, cancer and dental caries) of mankind's keypoint control (Petersen.,
2003)。
At present generally acknowledged etiology of dental caries theory is four kinds of " tetrad factor theory ", i.e. antibacterial, oral environment, host and time
Factor result in dental caries jointly.Oral temperature is suitable, is the procreation of flora in oral cavity containing alkalescence saliva, food debriss etc.
There is provided suitable environment (Loesche., 1986).Antibacterial is the pathogenetic necessary factor of dental caries, antibacterial and food debriss in oral cavity
And saliva mixing, in firmly sticking to dental surface and nest ditch, plaque bio-film is formed, become dental caries pathogenetic initial
Condition.Both at home and abroad many scholars have confirmed that deformation bacterium (Streptococcus mutans) of practising a ball game is to cause dental caries topmost
Pathogen.Streptococcus mutans are a kind of Gram-positive anaerobic bacteria, its cariogenicity and its adhesion, sour, the acidproof and born of the same parents of product
The processes such as exo polysaccharides synthesis it is relevant (Hamad and Slade., 1980).Streptococcus mutans produce glucanotransferase metabolism sugar
And glucose and Fructose are aggregated into into glucosan and levan, dextran molecule amount is high, viscosity is big, and its absorption is on tooth and is situated between
Lead other floras in Streptococcus mutans and oral cavity and assemble and adhere to dental surface formation bacterial plaque, in bacterial plaque environment hammer is deformed
Bacterium produce organic acid, reduce oral environment pH value, make enamel and decalcification of dentine so as to formed dental caries (Lemos et al.,
2013).Meanwhile, Streptococcus mutans still can survive and metabolism carbohydrate in low ph environment, relative in oral cavity
Other antibacterials have growth vigor.
From the twentieth century middle period, fluoride is just used to preventing decayed tooth, and fluoride can be promoted again by reducing enamel decalcification
Secondary mineralising, produces the mechanism such as suppression and killing action and carrys out pre- anti-caries to microorganism.Therefore fluoride is widely used in dental caries
Clinical treatment, but result in the selective growth of F resistant Strain.The product acid of Streptococcus mutans F resistant Strain and acid-fast ability
It is all strong than parental strain, cariogenic potential also strengthen (Van Loveren et al., 1993).The appearance of F resistant Strain is to fluoride
Prophylactic treatment dental caries propose new problem, and prevention and the research and development of the New Measure and medicine for the treatment of dental caries become very urgent.
The content of the invention
For the demand of prior art, it is an object of the invention to provide a kind of novel thiazole that can suppress Streptococcus mutans
Class compound and its application.
The thiazole compound XQH-3-6 of Streptococcus mutans of the present invention, it is characterised in that：The compound chemistry point
Minor is C16H16ClN5O4S, Chinese is N1- (3- chlorphenyl-N4- (5- nitrothiazole -2- bases)) piperidines-formyl of Isosorbide-5-Nitrae-two
Amine, English name is N1- (3-chlorophenyl)-N4- (5-nitrothiazol-2-yl) piperidine-1,4-
Dicarboxamide, molecular weight is 409.85, shown in its chemical constitution such as formula (1)：
Above-claimed cpd is soluble in dimethyl sulfoxide (DMSO), is insoluble in water.
The synthetic route of above-claimed cpd XQH-3-6 is shown in following reaction equation
Wherein：(a) I-hydroxybenzotriazole (HOBT), 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides
(EDCI), triethylamine, room temperature；(b) ethyl acetate hydrogen chloride saturated solution, room temperature；Or trifluoroacetic acid/dichloromethane；(d) three
Phosgene, anhydrous ethyl acetate, 0 DEG C to backflow；(e) triethylamine, anhydrous tetrahydro furan, 0 DEG C is arrived room temperature.
Thiazole compound XQH-3-6 of the present invention is preparing suppression and is killing Streptococcus mutans (Streptococcus
Mutans) the application in the planktonic cells medicine of type strain and clinical strains.
Thiazole compound XQH-3-6 of the present invention is preparing suppression Streptococcus mutans (Streptococcus
Mutans) type strain and the biomembranous application formed in medicine of clinical strains.
Thiazole compound XQH-3-6 of the present invention is preparing oral cavity Streptococcus mutans (Streptococcus
Mutans) the application in bioflm inhibiting agents.
Applications of the thiazole compound XQH-3-6 of the present invention in the targeted drug for preventing and treating dental caries is prepared.
Thiazole compound XQH-3-6 of the present invention is preparing toothpaste, collutory or sterilization as antibacterial adding ingredient
Application in liquid.
By the compounds X QH-3-6 dmso solutions of powder, and it is made into the mother solution of final concentration of 1024mg/L
Storage.
The present invention determines compounds X QH-3-6 to Streptococcus mutans type strain and the inhibition of clinical strains.
As a result show, compounds X QH-3-6 has good bacteriostatic activity to the Streptococcus mutans under floating state and kills
Bacterium activity, its minimal inhibitory concentration (MIC) to Streptococcus mutans UA159 bacterial strains is 4mg/L, and minimal bactericidal concentration (MBC) is
8mg/L, half maximum suppression concentration (IC50) it is 0.963mg/L.When compounds X QH-3-6 final concentrations reach 4mg/L in culture medium
When to the biomembranous suppression ratio of Streptococcus mutans UA159 bacterial strains be 97.69%.Compounds X QH-3-6 is to Streptococcus mutans UA246
The minimal inhibitory concentration (MIC) of bacterial strain be 4mg/L, minimal bactericidal concentration (MBC) be 32mg/L, half maximum suppression concentration
(IC50) it is 1.505mg/L.When compounds X QH-3-6 final concentrations reach 4mg/L in culture medium to Streptococcus mutans UA246 bacterium
The biomembranous suppression ratio of strain is 97.93%.
Wherein, the Streptococcus mutans UA159 bacterial strains for being used are type strain, in ncbi database (http://
Www.ncbi.nlm.nih.gov/ the reference gene group # in) is NC_004350.Streptococcus mutans used in the present invention
UA246 bacterial strains are to be isolated from the clinical strains in the middle of the oral cavity with dental caries patient.Its preferred brain heart infusion of most suitable culture medium
(Brain Heart Infusion) culture medium (Brain infusion solids 12.5g/L, Beef heart
Infusion solids 5.0g/L, Proteose peptone 10.0g/L, Glucose 2.0g/L, Sodium
Chloride 5.0g/L, Di-sodium phosphate 2.5g/L, pH 7.4 ± 0.2), at 37 DEG C, Anaerobic culturel it is most suitable
Quiescent culture under the conditions of preferably.
Thiazole compound XQH-3-6 molecular weight disclosed by the invention is little, structure is relatively easy, and bacteriostatic experiment confirms have
The features such as strong inhibition capability, fragmentation effect are good, can significantly inhibit the Main Pathogenic Bacteria of dental caries --- Streptococcus mutans planktonic cells
Growth and biomembranous formation, the potentiality with anticaries can be used as pre- anticariogenic novel targeted drug candidate.
Specific embodiment
With reference to the present invention provide a kind of Streptococcus mutans novel thiazole class compound, further describe its
Kill, suppress Streptococcus mutans planktonic cells and its application during biofilm formation.The content is the solution to the present invention
Release rather than limit.
Embodiment 1：The preparation of compounds X QH-3-6
The synthetic route of compounds X QH-3-6 is shown in following reaction equation：
Wherein：(a) I-hydroxybenzotriazole (HOBT), 1- (3- dimethylamino-propyls) -3- ethyl-carbodiimide hydrochlorides
(EDCI), triethylamine, room temperature；(b) ethyl acetate hydrogen chloride saturated solution, room temperature；Or trifluoroacetic acid/dichloromethane；(d) three
Phosgene, anhydrous ethyl acetate, 0 DEG C to backflow；(e) triethylamine, anhydrous tetrahydro furan, 0 DEG C is arrived room temperature.
Involved solvent such as needs drying in course of reaction, then be dried process according to conventional standard drying method.
Concrete course of reaction：
(1) the intermediate 4- tert-butyl groups-(preparation of (5- nitrothiazole -2- bases) carbamyl -1- carboxylic acids (1).
1-Boc-4- piperidine carboxylic acids (1eq) are dissolved in into DMF, then be separately added into HOBt (1.2eq) and
EDCI (1.2eq), Deca triethylamine (1.2eq), completion of dropping adds 5- nitro thiazolamines (1.2eq), at normal temperatures
Reaction overnight, adds the distilled water of 200ml, water to be mutually extracted with ethyl acetate three times (3 × 200ml) in reactant liquor, merges organic
Washed (2 × 100ml) twice with saturation NaCl, anhydrous magnesium sulfate is dried, and then obtains crude product with Rotary Evaporators evaporation and concentration.Slightly
Product Jing silica gel chromatographic columns column purification separates (dichloromethane:Methanol=v:v,200:1) yellow solid, yield 75% are obtained.
(2) preparation of intermediate 2- (4- amino -1- bases)-N- (5- nitrothiazole -2- bases) piperidines -4- Methanamides (2).
Method 1：Chloroacetic chloride is slowly instilled (v in dehydrated alcohol:v,4:5), HCl and ethyl acetate are generated, then by upper one
Step intermediate is dissolved in wherein, stirs 15 minutes at normal temperatures, and complete with TLC detection reactions, solvent evaporated obtains yellow solid, slightly
Product yield 100%, it is unprocessed directly to carry out next step.
Method 2：Under ice bath, previous step intermediate is dissolved in a small amount of anhydrous methylene chloride, dropwise Deca trifluoroacetic acid
Solution (2eq), the solution is warmed naturally to after room temperature, continues to react 3 hours, has been finished to TLC monitoring reactions.Divide exactly organic
Solvent, the crude product of gained is unprocessed to be directly thrown in next step.
(3)N1- (3- chlorphenyl-N4It is prepared by-(5- nitrothiazole -2- bases) piperidines -1,4- diformamides (XQH-3-6).
During intermediate 3 (1eq) and triethylamine (1.2eq) are dissolved in into anhydrous tetrahydro furan at 0 DEG C, 3- chlorine is added dropwise
Phenyl isocyanate (1.2eq), stirs 3h, is reacted with TLC detections, steams tetrahydrofuran, and the distillation of 50ml is added in reactant liquor
Water, water is mutually extracted with ethyl acetate three times (3 × 50ml), merges organic faciess saturated nacl aqueous solution and washes (2 × 50ml) twice,
Anhydrous magnesium sulfate be dried 30 minutes, then Jing vacuum evaporations obtain crude product.Crude product Jing silica gel chromatographic columns (200～300 mesh) are pure
Change and separate, (dichloromethane:Methanol=50:1) as eluant, off-white powder is obtained, yield 67%,1H NMR(400MHz,
DMSO-d6)：δ 13.15 (s, 1H), 8.72 (s, 1H), 8.64 (s, 1H), 7.66 (s, 1H), 7.40 (d, J=8.2Hz, 1H),
7.25 (t, J=8.1Hz, 1H), 6.97 (d, J=7.8Hz, 1H), 4.16 (d, J=13.3Hz, 2H), 2.95-2.77 (m, 3H),
1.91 (d, J=11.3Hz, 2H), 1.59 (m, 2H) .ESI-MS:409.9[M+H].
Embodiment 2：The preparation of Streptococcus mutans
(1) culture medium for cultivating Streptococcus mutans is brain heart infusion (Brain Heart Infusion) culture medium (brand
OXOID, article No. CM1135), culture medium main component is Brain infusion solids 12.5g/L, Beef heart
Infusion solids 5.0g/L, Proteose peptone 10.0g/L, Glucose 2.0g/L, Sodium
Chloride 5.0g/L, Di-sodium phosphate2.5g/L, pH 7.4 ± 0.2.Solid medium is such as needed, then needs to add again
The agar powder for plus 1.5%.115 DEG C of moist heat sterilization 30min, it is stand-by after cooling.
(2) it is brain heart infusion-sucrose medium to cultivate the biomembranous culture medium of Streptococcus mutans.Compound method is by sucrose
20% stock solution and the sterile filters filtration sterilization with 0.22 μm are made into, final concentration of 1% is added in brain-heart infusion medium
Sucrose.
(3) bacterium solution of Streptococcus mutans type strain UA159 and clinical strains UA246 is inoculated in into the training of brain heart infusion solid
On foster base and rule, in 37 DEG C, anaerobism is inverted culture 24 hours, obvious single bacterium colony occurs.
(4) single bacterium colony of one Streptococcus mutans UA159 and UA246 bacterial strain of picking, inoculation are distinguished with aseptic inoculating loop
To in the test tube equipped with brain heart infusion fluid medium, the anaerobism static gas wave refrigerator at 37 DEG C is muddy to examination liquid in pipe.
(5) Streptococcus mutans UA159 and UA246 is determined respectively in 600nm wavelength with ultra-violet and visible spectrophotometer
Absorption value (OD600).
(6) compounds X QH-3-6 analytical balance accurate weighings, add dimethyl sulfoxide to be dissolved, and being made into concentration is
The stock solution of 1024mg/L, using 0.22 μm of sterile filters filtration sterilization, deposit in -20 DEG C it is stand-by.
Embodiment 3：Activity determinations of the compounds X QH-2-92 to Streptococcus mutans planktonic cells
(1) Streptococcus mutans bacterium solution and compounds X QH-3-6 are prepared according to the method described in embodiment 2, by culture system
Logarithmic (log) phase (OD600=0.8～Streptococcus mutans UA159 and UA246 bacterium solution brain heart infusion fluid medium 1.0) is diluted to
Final concentration of 5 × 105Cfu/ml is stand-by.
(2) detections of the compounds X QH-3-6 to the minimal inhibitory concentration of Streptococcus mutans UA159 and UA246 planktonic cells
Using micro broth dilution method.Streptococcus mutans bacterium solution final concentration of 5 × 10 in each hole of aseptic 96 orifice plate5Cfu/ml,
The stock solution of the compounds X QH-3-6 for preparing as stated above is added in the first hole and be adjusted to final concentration of 256mg/L, mix
It is even, then draw 150 holes of μ l to the 2nd, draw 150 holes of μ l to the 3rd after mixing again, so continuous doubling dilution to the 11st hole, and
Draw 150 μ l from the 11st hole to discard.So far, the 1st to the 11st hole is the experimental group for adding medicinal liquid, and the 12nd hole is not dosing as life
Long matched group.1st hole is respectively 256,128,64,32,16,8,4,2,1,0.5,0.25,0 μ g/ml to the 12nd hole drug level.
To completely inhibit least concentration positioning minimal inhibitory concentration (MIC) of bacterial growth in aperture.
(3) after taking the bacterium solution even spread in hole on brain heart infusion agar solid medium, 37 DEG C of anaerobism are inverted culture
24 hours, with positioning minimal bactericidal concentration of the least concentration without bacterial growth (MBC).
(4) with each interior absorbance under 600nm wavelength of 96 orifice plates of microplate reader detection, each drug level bar is calculated
The suppression ratio of cell under part, computing formula is suppression ratio=(1- experimental grouies/growth control group) × 100%, and the data obtained is used
SPSS statistical softwares calculate half maximum suppression concentration (IC50), experimental result is as shown in table 1.
Activity determinations of the compounds X QH-3-6 of table 1. to Streptococcus mutans UA159 and UA246 planktonic cells
In table 1, MIC：Minimal inhibitory concentration；MBC：Minimal bactericidal concentration；IC50：Half maximum suppression concentration
From table 1 it will be seen that compounds X QH-3-6 has very to Streptococcus mutans UA159 and UA246 planktonic cells
Sterilization well and bacteriostatic activity.Compounds X QH-3-6 will be significantly better than deformation to the activity of Streptococcus mutans UA159 planktonic cells
Streptococcus UA246.
Embodiment 4：Compounds X QH-2-92 is to the biomembranous inhibitory activity of Streptococcus mutans
(1) prepare Streptococcus mutans bacterium solution and compounds X QH-3-6 according to the method described in embodiment 1 and 2, use the brain heart
Streptococcus mutans in logarithmic (log) phase are diluted to final concentration of 5 × 10 by immersion-sucrose medium5Cfu/ml is stand-by.
(2) the μ l of bacterium solution 150 in (1) are added in 96 aseptic orifice plates, and to add the hole of compounds X QH-3-6 (whole
Concentration 4mg/L) as experimental group, be not added with compounds X QH-3-6 hole as a control group.It is little in 37 DEG C of anaerobism quiescent cultures 40
When.
(3) planktonic cells in each hole of 96 orifice plates are removed, and is rinsed to remove unadsorbed cell with substantial amounts of water.
(4) add the crystal violet solution of 200 μ l 0.1% to be dyeed at room temperature in each hole, stand and moved after 5min
Crystal violet solution is walked, and the unadsorbed crystal violet solution of removing is rinsed out with a large amount of water.
(5) add the acetic acid solution of 200 μ l 33% in each hole to dissolve the crystal violet of absorption, then using enzyme mark
Instrument detects the absorbance under 590nm wavelength, calculates biomembranous suppression ratio, and computing formula is with embodiment 1.
As a result show, it is biological to Streptococcus mutans UA159 bacterial strains when compounds X QH-2-6 reaches 4mg/L in culture medium
The suppression ratio of film is 97.93%, is 97.69% to the biomembranous suppression ratio of Streptococcus mutans UA246 bacterial strains.
Claims (6)
1. the thiazole compound XQH-3-6 of a kind of Streptococcus mutans, it is characterised in that：The compound chemical molecular formula is
C16H16ClN5O4S, Chinese is N1- (3- chlorphenyl-N4- (5- nitrothiazole -2- bases)) piperidines-Isosorbide-5-Nitrae-diformamide, English
Entitled N1- (3-chlorophenyl)-N4- (5-nitrothiazol-2-yl) piperidine-1,4-
Dicarboxamide, molecular weight is 409.85, shown in its chemical constitution such as formula (1)：
2. thiazole compound XQH-3-6 described in claim 1 is preparing suppression and is killing Streptococcus mutans
Application in the planktonic cells medicine of (Streptococcus mutans) type strain and clinical strains.
3. thiazole compound XQH-3-6 described in claim 1 is preparing suppression Streptococcus mutans (Streptococcus
Mutans) type strain and the biomembranous application formed in medicine of clinical strains.
4. thiazole compound XQH-3-6 described in claim 1 is preparing oral cavity Streptococcus mutans (Streptococcus
Mutans) the application in bioflm inhibiting agents.
5. applications of the thiazole compound XQH-3-6 described in claim 1 in the targeted drug for preventing and treating dental caries is prepared.
6. thiazole compound XQH-3-6 described in claim 1 is preparing toothpaste, collutory or sterilization as antibacterial adding ingredient
Application in liquid.
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Cited By (7)
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|---|---|---|---|---|
| CN108078822A (en) * | 2018-01-17 | 2018-05-29 | 山东大学 | A kind of morning-night special type toothpaste |
| CN108210385A (en) * | 2018-01-17 | 2018-06-29 | 山东大学 | A kind of g., jelly-like mouthwash with preventing decayed tooth antibacterial and strong root permanent tooth |
| CN108685911A (en) * | 2018-08-14 | 2018-10-23 | 山东大学 | 2-[(4- tertiary butyl thiazole -2- bases) Ya Anji ]Application of the thiazolin 4 one in pharmacy |
| CN109503510A (en) * | 2019-01-03 | 2019-03-22 | 山东大学 | A kind of thiazole compound and preparation method thereof of preventing decayed tooth antibacterial |
| CN109503569A (en) * | 2019-01-03 | 2019-03-22 | 山东大学 | Thiazole derivative and its preparation method and application |
| CN112174943A (en) * | 2019-07-03 | 2021-01-05 | 四川大学 | Application of indole-2-ketone compound in preparation of oral bacteria prevention and treatment product |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998005332A1 (en) * | 1996-08-01 | 1998-02-12 | Isis Pharmaceuticals, Inc. | Novel heterocycle compositions |
| WO2014179144A1 (en) * | 2013-04-29 | 2014-11-06 | E. I. Du Pont De Nemours And Company | Fungicidal heterocyclic compounds |
-
2016
- 2016-12-14 CN CN201611155086.0A patent/CN106588911B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998005332A1 (en) * | 1996-08-01 | 1998-02-12 | Isis Pharmaceuticals, Inc. | Novel heterocycle compositions |
| WO2014179144A1 (en) * | 2013-04-29 | 2014-11-06 | E. I. Du Pont De Nemours And Company | Fungicidal heterocyclic compounds |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108078822A (en) * | 2018-01-17 | 2018-05-29 | 山东大学 | A kind of morning-night special type toothpaste |
| CN108210385A (en) * | 2018-01-17 | 2018-06-29 | 山东大学 | A kind of g., jelly-like mouthwash with preventing decayed tooth antibacterial and strong root permanent tooth |
| CN108210385B (en) * | 2018-01-17 | 2020-08-18 | 山东大学 | A jelly-like collutory with effects of preventing dental caries, resisting bacteria, strengthening root and consolidating teeth |
| CN108685911A (en) * | 2018-08-14 | 2018-10-23 | 山东大学 | 2-[(4- tertiary butyl thiazole -2- bases) Ya Anji ]Application of the thiazolin 4 one in pharmacy |
| CN108685911B (en) * | 2018-08-14 | 2020-06-26 | 山东大学 | Application of 2- [ (4-tert-butylthiazole-2-yl) imino ] thiazoline-4-one in pharmacy |
| CN109503510A (en) * | 2019-01-03 | 2019-03-22 | 山东大学 | A kind of thiazole compound and preparation method thereof of preventing decayed tooth antibacterial |
| CN109503569A (en) * | 2019-01-03 | 2019-03-22 | 山东大学 | Thiazole derivative and its preparation method and application |
| CN112174943A (en) * | 2019-07-03 | 2021-01-05 | 四川大学 | Application of indole-2-ketone compound in preparation of oral bacteria prevention and treatment product |
| CN116440077A (en) * | 2023-03-15 | 2023-07-18 | 山东大学 | Oral spray for preventing and rapidly diagnosing and treating caries and preparation method thereof |
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| CN106588911B (en) | 2019-01-18 |
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