Bisabolol microcapsules are in being used to prepare the pharmaceutical composition for inhibiting streptococcus mutans
Purposes and bactericidal composition
Technical field
The present invention relates to chemical medicine fields, and in particular to bisabolol microcapsules and preparation method thereof and bisabolol are micro-
Capsule is in the purposes being used to prepare in the pharmaceutical composition for inhibiting streptococcus mutans.
Background technique
Streptococcus mutans (Streptococcus mutans) are the coccus of Gram-positive, are oral cavity natural floras
One of middle maximum streptococcus of accounting example.In streptococcus mutans group, streptococcus mutans and streptococcus sobrinus (fine hair hammer
Bacterium) it is closely related with the generation of human caries.Confirmation is studied repeatedly, and streptococcus mutans can cause rodent and spirit long
The animal model of animal experimental dental caries, while also evidence suggests the bacterium and human caries are closely related.Streptococcus mutans are
One of main component of dental plaque, they are adsorbed on tooth layer by layer, are formed so-called " biomembrane ", consume carbohydrate, produce
Raw acid, corrodes the glaze layer of tooth, causes dental cavity.
Bisabolol (CAS NO.:515-69-5) is to be present in one of yellow chamomile composition, has antiinflammation,
It can be applicable in skin sparing and skin care cosmetics and dental health product.
Bisabolol is colourless to straw Huang thick liquid, is dissolved in lower alcohol (ethyl alcohol, isopropanol), fatty alcohol, glyceride
With stone vinegar, almost insoluble in water and glycerol, therefore, bisabolol is difficult to disperse in water-solubility carrier, and which has limited it in aqua
Application in class product.
There are the related patents of some skin care compositions and methods containing bisabolol to report at present, however in these compositions
In, bisabolol is intended only as auxiliary element addition, is not utilized well.
In addition, though the known dispersibility that can improve certain active constituents using microcapsules technology, but specific to certain
Whether its dispersion effect of specific active constituent is not it is contemplated that having after especially improving dispersibility for corresponding function effect
It is promoted and promotes how degree is also not expected.
The present inventor has found that the microcapsules that bisabolol is formed under given conditions have in studying for a long period of time and exceeds to anticipate
The excellent stability of material and for specific bacteria have the unexpected fungistatic effect significantly improved, this hair is proposed based on this
It is bright.
Summary of the invention
It is good and to specific the technical problem to be solved by the present invention is to overcome the deficiencies of the prior art and provide a kind of stability
Bacterium has the bisabolol microcapsules of significant fungistatic effect.
Present invention simultaneously provides above-mentioned bisabolol microcapsules to be used to prepare the pharmaceutical composition for inhibiting streptococcus mutans
In purposes.
In order to solve the above technical problems, the technical solution adopted by the present invention is as follows:
A kind of bisabolol microcapsules, the composition of raw materials of the microcapsules include bisabolol, mineral oil and/or vegetable oil,
Emulsifier, polyethylene glycol series microcapsule matrix and water, wherein bisabolol, emulsifier and polyethylene glycol series microcapsules base
The mass ratio of matter is 0.05-0.2:0.8-3.2:0.8-8;
The microcapsules are made by following steps:
(1) bisabolol is added in mineral oil and/or vegetable oil, it is the red of 0.1-1% concentration that mass concentration, which is made,
Bisabol oil solution;
(2) microcapsule matrix and emulsifier is soluble in water, microcapsule matrix is made and emulsifier mass concentration is respectively
The aqueous solution of 8-15% and 2-6%;
(3) bisabolol oil solution obtained by step (1) is mixed and stirred for step (2) obtained aqueous solution, wherein controlling
Mixing speed is 20000~28000rpm, and mixing time is 1-10 minutes.
Preferably, in step (1), the mass concentration for controlling the bisabolol oil solution is 0.3-0.6%.Step (2)
In, the mass concentration that microcapsule matrix in aqueous solution is made is 9-11%.In step (2), the matter of emulsifier in aqueous solution is made
Amount concentration is 3-5%.
According to a preferred aspect of the present invention, in step (3), using FLUKO not Luke F25 high-shearing dispersion emulsifying machine
(abbreviation Fluko F25 blender) is stirred.
According to a further preferred aspect of the invention, in step (3), control mixing speed is 28000rpm, and mixing time is
3-5 minutes.
According to the present invention, the mineral oil includes but is not limited to methyl-silicone oil and/or paraffin oil, the vegetable oil include but
It is not limited to sunflower oil, corn oil, olive oil, castor oil, rapeseed oil, soybean oil, peanut oil etc..When practical selection, it can be used
Either of which kind or a variety of combinations, are not particularly limited.
According to the present invention, the emulsifier be preferably Span, tween, sodium long chain alkyl sulfonate, chain alkyl benzene sulfonic acid sodium salt,
One of lecithin, Fabaceous Lecithin, laureth sulfuric ester, Triton X-100 a variety of are formed with arbitrary proportion
Mixture.Wherein " sodium long chain alkyl sulfonate ", the chain alkyl in " chain alkyl benzene sulfonic acid sodium salt " refer to carbon number 12 with
On alkyl.According to a specific preferred aspect, the emulsifier is dodecyl sodium sulfate (SDS).
According to the present invention, the polyethylene glycol series microcapsule matrix can be for selected from polyethylene glycol 200, polyethylene glycol
300, polyethylene glycol 400, Macrogol 600, polyethylene glycol-800, cetomacrogol 1000, polyethylene glycol 1500, polyethylene glycol
2000, one of Macrogol 3000, Macrogol 4000, Macrogol 6000, PEG 8000 or a variety of with any
The mixture of ratio composition.According to a specific preferred aspect, microcapsules base is used as using cetomacrogol 1000 (PEG1000)
Matter.
According to a preferred embodiment of the invention, the microcapsules are made by following steps:
(1) bisabolol is added in sunflower oil, it is molten that the bisabolol oil that mass concentration is 0.3-0.6% is made
Liquid;
(2 is soluble in water by cetomacrogol 1000 and dodecyl sodium sulfate, and cetomacrogol 1000 and dodecyl sulphur is made
Sour sodium mass concentration is respectively the aqueous solution of 9-11% and 3-5%;
(3) bisabolol oil solution obtained by step (1) is mixed and stirred for step (2) obtained aqueous solution, wherein using
Not Luke F25 high-shearing dispersion emulsifying machine is stirred FLUKO, and controlling mixing speed is 25000~28000rpm, stirring
Time is 3-5 minutes.
According to the present invention, the Average Particle Diameters of the microcapsules be 10-40 microns, preferably 10-30 microns, more preferably
It is 10-20 microns.Difference between the maximum particle diameter and minimum grain size of the microcapsules is within 30 microns, preferably at 20 microns
Within.
Bisabolol microcapsules of the invention compare bisabolol oil solution, significant for the fungistatic effect of streptococcus mutans
It improves, produces unexpected effect.
Due to the implementation of above technical scheme, the invention has the following advantages over the prior art:
Bisabolol microcapsules provided by the invention have unexpected excellent stability, can significantly improve opopanax
The dispersibility of alcohol in water, and bisabolol oil solution is compared, the fungistatic effect of streptococcus mutans is significantly improved, is suitable for
Aqua class cleaning agent for mouth cavity is made, oral plaque, saprodontia are prevented.
Detailed description of the invention
Fig. 1 is the microscope figure that the preparation of each embodiment samples observation immediately after the completion;
Fig. 2 is the grain size distribution drawn according to the case where sampling is observed immediately after the completion of the preparation of each embodiment;
Fig. 3 is that the preparation of each embodiment is completed and samples the microscope figure of observation after 24 hours static;
Fig. 4 is that the particle diameter distribution that the case where observing is drawn is sampled after completing according to the preparation of each embodiment and is 24 hours static
Figure;
Fig. 5 is that the preparation of each embodiment is completed and samples the microscope figure of observation after 48 hours static;
Fig. 6 is that the particle diameter distribution that the case where observing is drawn is sampled after completing according to the preparation of each embodiment and is 48 hours static
Figure;
Fig. 7 is that the preparation of each embodiment is completed and samples the microscope figure of observation after 15 days static;
Fig. 8 is the microscope figure of rear sampling observation after the preparation of each embodiment is completed and is 28 days static;
Fig. 9 is the histogram drawn according to the experimental data of embodiment 4.
Specific embodiment
The present invention will be further described in detail combined with specific embodiments below, but the present invention is not limited to following implementations
Example.The condition being not specified in embodiment is conventional laboratory conditions.
Raw material: PEG1000 (pharmaceutical grade), sunflower oil (food-grade), bisabolol (pharmaceutical grade), lauryl sodium sulfate
(SDS) (pharmaceutical grade);Instrument: Fluko F25 blender, 8G work head (operation sample size 1-60ml) are provided.
To the characterizing method of microcapsules are as follows: take 5 microlitres of upper layer drops, drip in glass sheet surface, after droplet distribution is opened (about
30s), amplify 200 times of shooting drop photos under microscope, analysis of the droplet size draws grain size distribution.
The preparation of the pure bisabolol microcapsules of embodiment 1
(1) 50mg bisabolol is mixed into sunflower oil, 0.5% (w/w) bisabolol oil solution of total amount 10g is made
(solution A);
(2) SDS of the PEG1000 of 4g and 1.6g is dissolved in deionized water with 10% (w/w) and 4% (w/w) respectively,
The aqueous solution (solution B) of total amount 40g is made;
(3) it after mixing 10g solution A in aseptic beaker with 40g solution B, is stirred with Fluko F25, if
Determining mixing speed is 28000rpm, mixing time 1 minute, and after the completion of stirring, sampling is observed immediately, relevant picture and particle diameter distribution
Figure is respectively referring to Figure 1A and Fig. 2A, and after sample static 24 hours, the observation of the second sub-sampling, relevant picture and grain size distribution are distinguished
Referring to Fig. 3 A and Fig. 4 A.After static 48 hours of sample, the observation of third sub-sampling, relevant picture and grain size distribution are respectively referring to figure
5A and Fig. 6 A.After static 15 days of sample, the observation of the 4th sub-sampling, relevant picture is referring to Fig. 7 A.After static 28 days of sample, the 5th time
Sampling observation, relevant picture is referring to Fig. 8 A.
The preparation of the pure bisabolol microcapsules of embodiment 2-3
Embodiment 2-3 substantially with embodiment 1, unlike, setting mixing time is respectively 3 minutes and 5 minutes, wherein
Embodiment 2 prepare microcapsules after completion of stirring, it is 24 hours static after, it is 48 hours static after, 15 days and the photograph after 28 days
Piece respectively referring to Figure 1B, Fig. 3 B, Fig. 5 B, Fig. 7 B and Fig. 8 B, after the completion of stirring, it is 24 hours static after, it is 48 hours static after grain
Diameter distribution map distinguishes B, 4B, Fig. 6 B referring to fig. 2.Embodiment 3 prepare microcapsules after completion of stirring, it is 24 hours static after, it is quiet
Only after 48 hours, 15 days and the photo after 28 days be respectively referring to Fig. 1 C, Fig. 3 C, Fig. 5 C, Fig. 7 C and Fig. 8 C, after the completion of stirring,
After static 24 hours, it is 48 hours static after grain size distribution C, 4C and Fig. 6 C referring to fig. 2 respectively.
The experiment of the pure bisabolol microcapsule antibacterial of embodiment 4
(1) preparation of experimental drug:
Microcapsules group: 3 gained microcapsules sample of embodiment.
Bisabolol control group: it is molten that 0.050g bisabolol is dissolved in the bisabolol oil formed in 49.95g sunflower oil
Liquid.
Ampicillin control group: the ampicillin 0.050g is dissolved in 49.95g (physiological saline of sterilizing)
Blank control element: the physiological saline only to sterilize.
(2) streptococcus mutans antibacterial experiment
1. reagent: BHI medium component: tryptone, disodium hydrogen phosphate, sodium chloride, glucose, cattle heart leachate, fine jade
Rouge, distilled water.
2. experimental procedure:
1. appropriate culture medium and bacterium solution is taken overnight, to dilute multiple appropriate in shaking table, plate count is planted.(deformation hammer
Bacterium initial concentration is about 5*108Cfu/ml);
2. taking 10000 times of physiological saline gradient dilution that Escherichia coli 0.01ml sterilizes before experiment;
3. taking the bacterium solution of above-mentioned drug solution 1ml and 0.02ml respectively, after concussion mixes, it is placed at room temperature for 15 minutes or 2 is small
When (be repeated 2 times test in parallel);
4. shaking uniformly after 15 minutes or 2 hours, above-mentioned sample (step 3) 0.3ml is taken to add the physiological saline of sterilizing dilute
It releases to 3ml.It after concussion mixes, takes 1ml in plate, suitable cool to 40'C-45 DEG C culture medium (each sample paving is then added
2 plates count);
5. after culture medium solidification after, back-off plate be put into containing nitrogen, carbon dioxide, hydrogen hermetic bag in 37 DEG C train
It supports in case, the counting of viable bacteria bacterium colony is done after 24 hours;
6. experiment is repeated twice, it is averaged.
3. experimental result (A, B are independent experiment twice)
The first time experiment of 3.1 pairs of streptococcus mutans, drug exposure times are divided into 15 minutes and 2 hours.Experimental period is
On January 12nd, 2017, as a result respectively referring to Tables 1 and 2.
Table 1
Table 2
Second of experiment of 3.2 pairs of streptococcus mutans, drug exposure times also 15 minutes and 2 hours.When experiment
Between be on January 14th, 2017, as a result respectively referring to table 3 and table 4.
Table 3
Table 4
The average value of each drug bacteriostasis rate is calculated by independent experiment twice and standard deviation compares, such as table 5 and 6
It is shown.
Table 5
Handle 15 minutes time Experimental comparison twice |
Bacteriostasis rate |
Bacteriostasis rate |
Average value |
Standard deviation |
Ampicillin sodium 1 |
100 |
100 |
100 |
0 |
Ampicillin sodium 2 |
100 |
100 |
100 |
0 |
Bisabolol oil solution 1 |
48 |
51 |
49.5 |
2.3 |
Bisabolol oil solution 2 |
61 |
58 |
59.5 |
1.8 |
0.5% bisabolol microcapsules 1 |
100 |
100 |
100 |
0 |
0.5% bisabolol microcapsules 2 |
100 |
100 |
100 |
0 |
Table 6
Handle time 2 h Experimental comparison twice |
Bacteriostasis rate |
Bacteriostasis rate |
Average value |
Standard deviation |
Ampicillin sodium 1 |
100 |
100 |
100 |
0 |
Ampicillin sodium 2 |
100 |
100 |
100 |
0 |
Bisabolol oil solution 1 |
61 |
58 |
59.5 |
1.8 |
Bisabolol oil solution 2 |
60 |
59 |
59.5 |
0.4 |
0.5% bisabolol microcapsules 1 |
100 |
100 |
100 |
0 |
0.5% bisabolol microcapsules 2 |
100 |
100 |
100 |
0 |
Histogram can be drawn by the comparison processing of experimental data, as shown in Figure 9.
The results show, 0.5% bisabolol microcapsules of the invention have what is significantly improved to resist compared to its oil solution
Bacterium effect, antibacterial effect can compare favourably with ampicillin sodium.
The above embodiments merely illustrate the technical concept and features of the present invention, and its object is to allow person skilled in the art
Scholar cans understand the content of the present invention and implement it accordingly, and it is not intended to limit the scope of the present invention.It is all according to the present invention
Equivalent change or modification made by Spirit Essence, should be covered by the protection scope of the present invention.