CN107998402A - A kind of preparation method and application of magnolol-c-terminus polyamide sustained release agent - Google Patents
A kind of preparation method and application of magnolol-c-terminus polyamide sustained release agent Download PDFInfo
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- CN107998402A CN107998402A CN201810042276.4A CN201810042276A CN107998402A CN 107998402 A CN107998402 A CN 107998402A CN 201810042276 A CN201810042276 A CN 201810042276A CN 107998402 A CN107998402 A CN 107998402A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/05—Phenols
Abstract
The invention discloses a kind of preparation method and application of magnolol c-terminus polyamide sustained release agent, preparation method comprises the following steps:It is 1 by volume by dimethyl sulfoxide (DMSO) and distilled water:7 are mixed, and obtain mixed solution;Mixed solution is taken, c-terminus polyamide is added in the ratio of 6mg/mL, magnolol is added in the ratio of 2.0mg/mL;Solution ultrasonic vibration, is then sufficiently stirred;Water centrifugation is added to remove precipitation, supernatant freezes to obtain required magnolol c-terminus polyamide sustained release agent, M PAMAM COOH;Preparation method of the present invention is easy to operate, feasibility is high;The M PAMAM COOH of preparation solve the applied defect of magnolol, high molecular material PAMAM COOH are combined with medicine, medicine can be played preferably to act on, extend pharmaceutical release time, beneficial to the application in clinic, it is inhibited to Streptococcus mutans and biomembrane, the prevention available for dental caries.
Description
Technical field
The present invention relates to dentistry Material Field, and in particular to a kind of system of magnolol-c-terminus polyamide sustained release agent
Preparation Method and application.
Background technology
Magnolol is the main active of Cortex Magnoliae Officinalis, and research finds to confirm that magnolol suppresses with nervous centralis, resists
Inflammation, antiulcer is antitumor, the pharmacological action such as antibacterial, in terms of antibacterial action, magnolol to Streptococcus mutans, actinomyces viscosus,
Dental caries correlation bacterium has stronger inhibitory action in the oral cavity such as Bacillus acidi lactici, Streptococcus sanguis, actinomyces naeslundii, wherein to Streptococcus mutans
Effect it is especially pronounced, minimum inhibitory concentration can suppress the formation of Streptococcus mutans biomembrane and subtract up to 15.7 μ g/mL
Few biomembrane formed, its activity and effect are superior to other Chinese medicines;Compared with traditional antibiotic, magnolol does not have
There is drug resistance, and it is strong to bacterial action;Although there is magnolol the defects of superior antibacterial activity, two aspects to limit
Its clinical practice;First, the phenolic hydroxyl group of magnolol is easily aoxidized, and preparation is preserved and is easily denatured, and is unfavorable for promoting;Second, medicine
Thing is insoluble in water, therefore, in view of the above-mentioned problems, the present invention provides a kind of dissolubility that can improve medicine and ensures medicine
Stability preparation method.
The content of the invention
The present invention provide a kind of magnolol of anti-oral cavity Streptococcus mutans-c-terminus polyamide sustained release agent preparation method and
Using.
The technical solution adopted by the present invention is:A kind of preparation method of magnolol-c-terminus polyamide sustained release agent, including with
Lower step:
(1)It is 1 by volume by dimethyl sulfoxide (DMSO) and distilled water:7 are mixed, and obtain mixed solution;
(2)Take step(1)In obtained mixed solution, c-terminus polyamide is added in the ratio of 6mg/mL, by 2.0mg/mL's
Ratio adds magnolol;
(3)By step(2)Obtained solution ultrasonic vibration, is then sufficiently stirred;
(4)Water centrifugation is added to remove precipitation, supernatant freezes to obtain required magnolol-c-terminus polyamide sustained release agent, M-PAMAM-
COOH。
Further, the step(3)Middle ultrasonic vibration and whipping process carry out under 37 DEG C of constant temperatures.
Further, the step(3)When middle ultrasonic vibration 1 is small, 72h is stirred under the conditions of 200rpm.
Further, the step(4)Middle centrifugal process handles 10min under the conditions of 3000rpm.
A kind of application of magnolol-c-terminus polyamide sustained release agent in dental caries medicine is prevented.
Further, the M-PAMAM-COOH can extend pharmaceutical release time.
Further, the M-PAMAM-COOH can inhibit Streptococcus mutans.
Further, the M-PAMAM-COOH can inhibit the formation of Streptococcus mutans biomembrane.
Further, the M-PAMAM-COOH can reduce Streptococcus mutans biomembrane.
The beneficial effects of the invention are as follows:
(1)Magnolol prepared by the present invention-c-terminus polyamide sustained release agent M-PAMAM-COOH, the application for solving magnolol lack
Fall into;
(2)Magnolol prepared by the present invention-c-terminus polyamide sustained release agent M-PAMAM-COOH extends pharmaceutical release time, profit
Application in clinic;
(3)Magnolol prepared by the present invention-c-terminus polyamide sustained release agent M-PAMAM-COOH, to Streptococcus mutans and biomembrane
It is inhibited, and magnolol does not have drug resistance compared with traditional antibiotic, and action effect is strong, available for the anti-of dental caries
Control;
(4)Preparation method of the present invention can improve the dissolubility of medicine and ensure the stability of medicine, and easy to operate,
Feasibility is high.
Brief description of the drawings
Fig. 1 is the DSC testing results of embodiment 1 in the present invention.
Fig. 2 is the NMR testing results of embodiment 2 in the present invention.
Fig. 3 is the M-PAMAM-COOH prepared in the present invention medicine releasing curve diagrams in buffer solution.
Fig. 4 is the growth curve chart of Streptococcus mutans flcating germ in embodiment 4 in the present invention.
Fig. 5 is the count plate of Streptococcus mutans flcating germ in embodiment 4 in the present invention.
Fig. 6 is the antibacterial action curve of Streptococcus mutans in embodiment 4 in the present invention.
Fig. 7 is the formation figure of Streptococcus mutans biomembrane in embodiment 4 in the present invention.
Fig. 8 is preparation method research process figure of the present invention.
Embodiment
The present invention will be further described with specific embodiment below in conjunction with the accompanying drawings.
By preparing the research of sustained release agent method and the tune of relevant parameter to water soluble method, organic solvent method and common molten three kinds of method
It is whole, obtain the M-PAMAM-COOH sustained release agents with excellent carrier medicine carrying efficiency;By the adjustment of distinct methods and different parameters condition,
Obtain preparing the best approach and Parameter Conditions of magnolol-c-terminus polyamide sustained release agent, as shown in Figure 8.
A kind of preparation method of magnolol-c-terminus polyamide sustained release agent, comprises the following steps:
(1)It is 1 by volume by dimethyl sulfoxide (DMSO) and distilled water using mixed solvent method:7 are mixed, and obtain mixed solution;
(2)Take step(1)The mixed solution that middle 10mL is obtained is added in 15mL centrifuge tubes, and carboxyl is added in the ratio of 6mg/mL
Polyamide 6 0mg is held, magnolol 20mg is added in the ratio of 2.0mg/mL;
(3)By step(2)Obtained solution ultrasonic vibration, will centrifuge after duct occlusion ultrasonic vibration 1h at 37 DEG C, then from
Stirrer is put into heart pipe, closing is placed in 37 DEG C of constant temperature mixers stirs 72h with 200rpm;
(4)8mL water is added to precipitate extra medicinal, 3000rpm centrifugations 10min removes precipitation, and supernatant freezes to obtain required Cortex Magnoliae Officinalis
Phenol-c-terminus polyamide sustained release agent, M-PAMAM-COOH.
A kind of application of magnolol-c-terminus polyamide sustained release agent in dental caries medicine is prevented;The M-PAMAM-COOH
Magnolol release time can be extended;The M-PAMAM-COOH can inhibit Streptococcus mutans;The M-PAMAM-COOH can inhibit
The formation of Streptococcus mutans biomembrane;The M-PAMAM-COOH can reduce Streptococcus mutans biomembrane.
Embodiment 1
Differential scanning calorimetry DSC detections are carried out, sample to be tested is divided into four groups:C-terminus polyamide(PAMAM-COOH), it is thick
Plain phenol(M), magnolol and c-terminus polyamide mixture(M+ PAMAM-COOH)And M-PAMAM-COOH.
Detailed process is as follows:Every group of sample weighs 5mg respectively, is respectively put into aluminium planchet and closes, and carries out DSC inspections
Survey;Testing conditions are:Gas pressure 0.06Mpa ~ 0.1Mpa, gas flow 20mL/min ~ 40mL/min, scan sample, with 10
DEG C/programming rate of min scanning sample, scanning range is 50 DEG C ~ 300 DEG C, and scanning result uses Pyris Manager softwares point
Analysis is handled;As shown in Figure 1, as can be seen from the figure:PAMAM-COOH has no peak value in scanning temperature range, shows at this
Neither endothermic nor exothermic is not present in PAMAM-COOH in temperature range;Document prompts magnolol DSC collection of illustrative plates that thickness nearby occurs at 103 DEG C
The exothermic peak of plain phenol, it is consistent with magnolol group result in experiment;Magnolol mixes the scanning result of group with PAMAM-COOH 103
There is exothermic peak near DEG C, be the characteristic peak of magnolol;Do not occur the characteristic peak of magnolol in M-PAMAM-COOH group pictures, and
180 DEG C or so there is a peak value, prompt magnolol to be successfully loaded in PAMAM-COOH.
Embodiment 2
Nuclear magnetic resonance 1H NMR detections are carried out, sample to be tested is divided into three groups:C-terminus polyamide(PAMAM-COOH), magnolol
(M)And M-PAMAM-COOH;
Detailed process is as follows:Every group of sample weighs 5mg respectively, and the sample weighed is dissolved in 0.6mL heavy water respectively(D2O)In,
M is dissolved in deuterated dimethyl sulfoxide respectively(DMSO-d6)In;Then liquid is added in nuclear magnetic tube, nuclear magnetic tube is put into core
In magnetic resonance spectrometer, selection1H is detected sample, obtains nuclear magnetic spectrum, and collection of illustrative plates is carried out using MestReNova softwares
Analyzing and processing;As shown in Fig. 2, as can be seen from the figure:It is the NMR spectrum of each group sample in Fig. 2, A is the core of magnolol
Magnetic chart is composed, solvent D2, there is D in figure at 4.86ppm in O2, there is the wave crest of magnolol, Qi Tawei at 3.25ppm in the solvent peak of O
Put and do not occur wave crest;B be PAMAM-COOH nuclear magnetic spectrum, solvent D2, there is wave crest, wherein a at 4.86ppm in O, and b is
Its characteristic peak.D is the nuclear magnetic spectrum of magnolol, and 2.50ppm places are the solvent peak of DMSO-d6 in solvent DMSO-d6, Fig. 2, thickness
The characteristic peak positions of plain phenol come from document, are respectively 6.81ppm(H3), 6.90 ~ 6.96ppm(H4,6), 3.35ppm(H7),
5.90~5.97(H8), 5.06 ~ 5.09(H9), and Fig. 2-D results are consistent with document;C is M-PAMAM-COOH after load medicine success:
The nuclear magnetic spectrum of sustained release agent, from C figures as can be seen that not only there is the peak of PAMAM-COOH on figure, and the also feature of magnolol
Peak, therefore can prove that magnolol is successfully loaded in PAMAM-COOH.
Embodiment 3
External sustained release
Specific operation process is as follows:
The configuration of buffer solution:KH is added in 1L aqueous solutions2PO40.27g, Na2HPO41.42g, NaCl 8g, KCl 0.2g, are used
Dense NaOH or HCl adjust pH, prepare the PBS buffer of pH 7.0 and pH 5.5 respectively;
The drafting of standard curve:Prepare the magnolol PBS solution of 10 μ g/mL(PH 7.0 and pH 5.5)Each 5mL, is diluted to respectively
0 μ g/mL, 2 μ g/mL, 4 μ g/mL, 6 μ g/mL, 8 μ g/mL, 10 μ g/mL, it is measured using the multi-functional readout instrument of full wavelength scanner formula
Fluorescence intensity, the excitation wavelength of magnolol is 290nm, launch wavelength 345nm, makes the mark of magnolol concentration-fluorescence intensity
Directrix curve;
Sustained release process:Prepare the sustained release agent PBS solution of 3mg/mL(PH=7.0 and pH=5.5), take 1mL solution to be placed in bag filter(Point
The son amount of blocking=1000)In, bag filter is closed, and bag filter is placed in the PBS of 100mL, 37 DEG C of constant temperature are simultaneously stirred with 50 rpm
Mix, time point for 12h, 22h, 36h, 48h, 60h, 72h, 96h, 120h, 144h, 168h, 192h, 216h, 240h, 264h,
Liquid 0.5mL is respectively taken out during 288h, and adds the fresh PBS of 0.5mL(PH 7.0 and pH 5.5)Buffer solution;Liquid is taken out in test
Fluorescence intensity, and calculate according to magnolol concentration-Standardization curve for fluorescence intensity the release hundred of each sample each time point
Divide ratio, accumulate drug release rate=accumulation release amount of medicine/drugloading rate, and make drug release patterns, experiment is repeated 3 times;Such as figure
Shown in 3, as can be seen from the figure:Magnolol in M-PAMAM-COOH sustained release agents discharges speed in the PBS buffer of pH 7.0
For rate apparently higher than the rate of release in 5.5 buffer solutions of pH, this explanation pH is one of factor for influencing magnolol rate of release;
In the release profiles of M-PAMAM-COOH, 76.53% burst size release in preceding 72h, 72 ~ 144h in 288h during pH 7.0
Shallower, cumulative release about 19%, and insoluble drug release is slower in 144h ~ 192h, cumulative release about 4%, during to 240h, medicine is basic
Release is complete, hereafter substantially without insoluble drug release;During pH 5.5 in 288h 64.63% burst size in preceding 96h, 96h ~ 240h medicines
Release is slightly slow, and cumulative release is slower up to 30%, 240h ~ 268h insoluble drug releases, and medicine discharges completely substantially;
The excitation wavelength of magnolol is 290nm, launch wavelength 345nm.
Embodiment 4
M-PAMAM-COOH antibacterial experiments
1st, M-PAMAM-COOH acts on the growth curve of lower variation streptococcus flcating germ
The lyophilized sample of preparation is taken, weighs appropriate, M-PAMAM-COOH and PAMAM-COOH are dissolved in the super of sterilization
It is 60mg/mL to make its concentration in light-water DDW;M-PAMAM-COOH solution is diluted to 10mg/mL, 20mg/mL and 40mg/ again
mL;Weigh appropriate magnolol and be dissolved in ethanol(EtOH)In solution, concentration is respectively 157 μ g/mL;
It is prepared by bacteria suspension:Streptococcus mutans are inoculated in BHI solid mediums, 80%N after freezing strain recovery2, 20%CO2, at 37 DEG C
Anaerobic culturel 48h, checks colony growth form, and microscopy is pollution-free, and biochemical identification is 2 single bacterium colony difference of picking after pure culture
It is placed in the 15mL centrifuge tubes of 4mL BHI fluid nutrient mediums;80%N2, 20%CO2, overnight in anaerobiosis culture at 37 DEG C, next day is by bacterium
Take out, by 1: 20(v/v)Dilution culture 3h;Cultured bacterium solution is taken out again, bacterium solution is tested in 600nm using spectrophotometer
Under wavelengthODValue;Bacterial concentration is adjusted, is madeODValue is 0.5 or so(0.4~0.6)(WhenODBe worth for 0.5 when bacterial concentration be
108), it is stand-by by 1: 100 (v/v) dilutions that bacterial concentration bacterium solution will be adjusted.
Experiment is grouped:Blank control group:For pure culture base(BCG);Negative control group:DDW, 6mg/mL
PAMAM-COOH(NCG);Positive controls:15.7 μ g/mL magnolols(M);Solvent control group:10% ethanol(EtOH);Experiment
Group:The M-PAMAM-COOH of 1mg/mL, 2mg/mL, 4mg/mL, 6mg/mL, be expressed as in figure MP1, MP2, MP4 and
MP6。
Experiment packet sample is separately added into 200 μ L in 96 orifice plates, every group of 3 Duplicate Samples, then 96 orifice plates are put into enzyme
Mark in instrument, cultivated under 37 DEG C of constant temperature, the measure bacterium absorbance A per 30min(600nm), common 24h;As shown in figure 4, can from figure
To find out:(1)In M-PAMAM-COOH experiments, negative control group, PAMAM-COOH groups, the M- of solvent control group and 1mg/mL
No difference of science of statistics between PAMAM-COOH groups(P>0.05), show that PAMAM-COOH and solvent do not influence Streptococcus mutans growth;
(2)There were significant differences between the M-PAMAM-COOH groups and negative control group of 2mg/mL, 4mg/mL and 6mg/mL, and difference has system
Meter learns meaning(P<0.05), the M-PAMAM-COOH sustained release agents of Biao Ming≤2mg/mL, which have Streptococcus mutans growth, necessarily to be suppressed to make
With;(3)There were significant differences between the M-P (- COOH) group and magnolol MIC groups of 4mg/mL and 6mg/mL(P<0.05), Biao Ming≤
The inhibitory action that the M-PAMAM-COOH sustained release agents of 4mg/mL grow Streptococcus mutans is more than magnolol MIC groups.
2nd, M-PAMAM-COOH acts on the count plate of lower variation streptococcus flcating germ
It is sustained the collection of liquid:The M-PAMAM-COOH of 4mg/mL is taken respectively, is fitted into bag filter, and bottom liquid is 4mL BHI liquid
Culture medium, collects each sample in 0-24h(d1), 24-48h(d2), 48-72h(d3), 72-96h(d4), 96-120h(d5),
120-144h(d6), 144-168h(d7)Sustained release liquid in period, collects 4mL bottoms liquid in each period, then again
Add the fresh BHI fluid nutrient mediums of 4mL.
Bacteria Culture is identical with step 1;Adjust bacterium solutionODValue is 0.5 or so(0.4~0.6), then by bacterial concentration bacterium solution
By 1: 10(v/v)Dilute stand-by.
Experiment packet:It is divided into negative control group:DDW(NCG);Experimental group:The M-PAMAM-COOH of 4mg/mL and 6mg/mL
It is expressed as MP4 and MP6.
Take the prepared experiment packet samples of 5mL to add in 15mL centrifuge tubes, centrifuge tube is placed in 37 DEG C of constant temperature bacterium trainings
Support in case, with 150r/m speed uniform rotation;It is respectively 0h, 1h, 2h at time point, 4h, 6h, 8h, 18h, when 24h takes out 200 μ
L bacterium solutions;Bacterium solution is subjected to 10 times of continuous gradient dilutions with sterile DDW, then takes 200 μ L of dilution to be inoculated in BHI solid mediums;
Tablet is inverted and in 80%N2, 20%CO2, Anaerobic culturel 48h at 37 DEG C, plate count of the choosing colony number within 30 ~ 300,
Count Colony Forming Unit(Colony forming unit, CFU), CFU/mL=full flat-plate bacterial colony number × 5 × extension rate;
The results are shown in Figure 5 for its experiment, as can be seen from the figure:By comparing different time points CFU values, find(1)Negative control group
CFU shows a rising trend within 7 time points;The M-PAMAM-COOH of 4mg/mL and 6mg/mL CFU highests in 8h, during to 24h
Reduce;(2)The M-PAMAM-COOH effects lower variation streptococcus 24h CFU of 4mg/mL, 6mg/mL have compared with negative control group
Significant difference(P<0.05), show that growth of the sustained release agent to Streptococcus mutans has certain inhibitory action, the higher effect of concentration is more
By force.
3rd, M-PAMAM-COOH acts on the sustained anti-microbial effect of lower variation streptococcus flcating germ
The M-PAMAM-COOH of 4mg/mL is taken respectively, is fitted into bag filter, and bottom liquid is 4mL BHI fluid nutrient mediums, is collected each
Sample is in 0-24h(d1), 24-48h(d2), 48-72h(d3), 72-96h(d4), 96-120h(d5), 120-144h(d6),
144-168h(d7)Sustained release liquid in period;4mL bottoms liquid is collected in each period, then rejoins the fresh BHI of 4mL
Fluid nutrient medium.
The preparation of bacteria suspension as shown in step 1, adjusts bacterium solutionODValue is 0.5 or so(0.4~0.6), then by bacterial concentration bacterium
Liquid presses 1: 10(v/v)Dilute stand-by.
Experiment packet:It is divided into blank control group, pure culture base(BCG);Negative control group:DDW(NCG);Positive controls:
15.7 μ g/mL magnolols(M);Experimental group:The M-PAMAM-COOH sustained release liquids of d1 ~ d7.
Take 180 μ L to add in 96 orifice plates respectively the sustained-release liquid collected within the d1-d7 periods, add 20 μ L bacterium and hang
96 orifice plates, are put into microplate reader by liquid after having added sample;Cultivated under 37 DEG C of constant temperature, the measure bacterium absorption photometric A per 30min
(600nm), common 24h;96 orifice plates are taken out after 24h, bacterium solution are subjected to 10 times of continuous gradient dilutions with sterile DDW, then take dilution
200 μ L of liquid are inoculated in BHI solid mediums;Tablet is inverted in 80%N2, 20%CO2, Anaerobic culturel 48h at 37 DEG C;Choosing colony number
Plate count within 50 ~ 300, counts Colony Forming Unit CFU, CFU/mL=full flat-plate bacterial colony number × 5 × dilution times
Number;Experimental result is as shown in fig. 6, as can be seen from the figure:This experiment is mainly studied by turbidimetry and the method for plate culture count
The sustained release liquid of M-PAMAM-COOH influences bacterial growth, as a result such as Fig. 6, finds d1 ~ d7 groups and medicine MIC group growth rhythms
It is similar(Fig. 6), experimental group CFU is below negative control group and medicine MIC groups, and difference has statistical significance(P<0.05), table
Growth of the sustained release liquid of bright sustained release agent to Streptococcus mutans has certain inhibitory action, and its effect is better than medicine MIC groups.
4th, effects of the M-PAMAM-COOH to 48h Streptococcus mutans biofilm formations
According to flcating germ experimental result, choose M-PAMAM-COOH concentration and tested for 60mg/mL.
Experiment packet:It is divided into negative control group:DDW(M);The PAMAM-COOH of 6mg/mL;Experimental group:The M- of 6mg/mL
PAMAM-COOH。
Insert in the solution of experiment packet and soak after the hydroxylapatite plate of a diameter of 8mm, thickness 2mm are sterilized under ultraviolet lamp
Bubble, allows sustained release agent absorption on hydroxyapatite surface;It is after 10min that hydroxylapatite plate taking-up is unadsorbed with PBS flushing 1min removals
Sustained release agent, places drying;Dry hydroxy-apatite flag is inserted in 24 orifice plates, and adds 1mL bacteria suspensions, in 80%N2,20%
CO2, Anaerobic culturel 48h at 37 DEG C;Hydroxy-apatite flag is taken out after 48h, rinsing 1min with PBS removes non-adherent bacteria, puts
It is dry, under lucifuge 5 μ L fluorescent dyes are instilled in hydroxyapatite on piece;15min is placed under lucifuge, it is more to rinse 1min removals with PBS
Remaining dyestuff, puts dry;Streptococcus mutans biomembrane fluorescent staining situation, red fluorescence excitation wave are observed under Laser Scanning Confocal Microscope
Length/launch wavelength is 490/635nm, and green fluorescence excitation wavelength/launch wavelength is 480/500nm;The results are shown in Figure 7, from
It can be seen from the figure that:Effect of the sustained release agent to Streptococcus mutans biofilm formation mainly by by after biomembrane fluorescent staining,
The dyeing of bacterium is observed under laser confocal microscope and upgrowth situation is studied, and the results are shown in Figure 7, and wherein viable bacteria is in mirror
Under be rendered as green, dead bacterium is rendered as red, and orange is red green overlay region.Research finds, visible hydroxyl under blank control group mirror
Base apatite chip architecture, in green, no bacterium attachment;Visible 48h biomembranes three under negative control group and PAMAM-COOH group mirrors
The visible sustained release unit of dimension form result effectively reduces Streptococcus mutans biomembrane, as a result prompts sustained release agent to give birth to Streptococcus mutans
Thing film is inhibited.
Magnolol prepared by the present invention-c-terminus polyamide sustained release agent M-PAMAM-COOH, solves the application of magnolol
Defect;The magnolol of preparation-c-terminus polyamide sustained release agent M-PAMAM-COOH extends pharmaceutical release time, beneficial in clinic
Application;It is inhibited to Streptococcus mutans and biomembrane, and magnolol does not have drug resistance compared with traditional antibiotic,
And action effect is strong, the prevention available for dental caries;Preparation method of the present invention is easy to operate, feasibility is high.
Claims (9)
1. the preparation method of a kind of magnolol-c-terminus polyamide sustained release agent, it is characterised in that comprise the following steps:
(1) it is 1 by volume by dimethyl sulfoxide (DMSO) and distilled water:7 are mixed, and obtain mixed solution;
(2) mixed solution obtained in step (1) is taken, c-terminus polyamide is added in the ratio of 6mg/mL, by 2.0mg/mL's
Ratio adds magnolol;
(3) the solution ultrasonic vibration for obtaining step (2), is then sufficiently stirred;
(4) plus water centrifugation removes precipitation, and supernatant freezes to obtain required magnolol-c-terminus polyamide sustained release agent, M-PAMAM-
COOH。
A kind of 2. preparation method of magnolol according to claim 1-c-terminus polyamide sustained release agent, it is characterised in that
Ultrasonic vibration and whipping process carry out under 37 DEG C of constant temperatures in the step (3).
A kind of 3. preparation method of magnolol according to claim 1-c-terminus polyamide sustained release agent, it is characterised in that
When ultrasonic vibration 1 is small in the step (3), 72h is stirred under the conditions of 200rpm.
A kind of 4. preparation method of magnolol according to claim 1-c-terminus polyamide sustained release agent, it is characterised in that
Centrifugal process handles 10min under the conditions of 3000rpm in the step (4).
A kind of 5. application of magnolol-c-terminus polyamide sustained release agent in dental caries medicine is prevented as prepared by claim 1.
6. application according to claim 5, it is characterised in that when the M-PAMAM-COOH can extend magnolol release
Between.
7. application according to claim 5, it is characterised in that the M-PAMAM-COOH can inhibit Streptococcus mutans.
8. application according to claim 5, it is characterised in that the M-PAMAM-COOH can inhibit Streptococcus mutans biology
The formation of film.
9. application according to claim 5, it is characterised in that the M-PAMAM-COOH can reduce Streptococcus mutans biology
Film.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003055935A1 (en) * | 2001-12-21 | 2003-07-10 | Board Of Regents - The University Of Texas System | Dendritic poly (amino acid) carriers and methods of use |
CN103263437A (en) * | 2013-05-03 | 2013-08-28 | 华东师范大学 | Tree-type high-molecular polyamide-amine wrapped platinum nanometer particles, its preparation method and applications |
US20170028075A1 (en) * | 2010-03-31 | 2017-02-02 | Wayne State University | Injectable dendrimer hydrogel nanoparticles |
CN107115320A (en) * | 2017-04-13 | 2017-09-01 | 徐州医科大学附属医院 | A kind of targeted nano granule for loading Temozolomide and preparation method thereof |
-
2018
- 2018-01-17 CN CN201810042276.4A patent/CN107998402A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2003055935A1 (en) * | 2001-12-21 | 2003-07-10 | Board Of Regents - The University Of Texas System | Dendritic poly (amino acid) carriers and methods of use |
US20170028075A1 (en) * | 2010-03-31 | 2017-02-02 | Wayne State University | Injectable dendrimer hydrogel nanoparticles |
CN103263437A (en) * | 2013-05-03 | 2013-08-28 | 华东师范大学 | Tree-type high-molecular polyamide-amine wrapped platinum nanometer particles, its preparation method and applications |
CN107115320A (en) * | 2017-04-13 | 2017-09-01 | 徐州医科大学附属医院 | A kind of targeted nano granule for loading Temozolomide and preparation method thereof |
Non-Patent Citations (2)
Title |
---|
YAN ZHOU等: "Triclosan-loaded poly(amido amine) dendrimer for simultaneoustreatment and remineralization of human dentine", 《COLLOIDS AND SURFACES B: BIOINTERFACES》 * |
冯瑾等: "厚朴活性成分对致龋菌生长和产酸影响的体外研究", 《四川大学学报(医学版)》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110801442A (en) * | 2018-07-20 | 2020-02-18 | 复旦大学 | Slow-release microsphere coated with honokiol and pharmaceutical application thereof |
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