PH buffer activity glass and preparation method thereof and the purposes of preventing and treating oral disease
Technical field
The present invention relates to a kind of pH buffer activity glass.
Background technology
Bioactivity glass is clinically as oral cavity bone renovating material, orthopaedics the bone impairment renovation material applicating history in existing more than 15 year in worldwide.One of bioactivity glass characteristic is when bioactive glass particle contacts with liquid phase, and the accelerated surface reaction takes place, and its result is: 1, ion discharges; 2, calcium, phosphorus plasma deposition generate support shape hydroxyapatite layer, i.e. a bone mineralising phase on the bioactive glass particle surface.Recently new research shows; The characteristic of inducing the bone mineralising to form mutually of bioactivity glass can be induced the overglaze formation of new tooth on dental surface; Thereby reach the position that is corroded of sealing dentinal tubule, remedying tooth, reach desensitization and prevent the effect of tooth (list of references 1) in solitude.New research shows that simultaneously bioactivity glass has stronger bactericidal action in liquid environment, particularly oral cavity bacterium is had bactericidal action (list of references 2).
" bioactive glass compositions and the Therapeutic Method that uses bioactivity glass " (patent No. 97193085) (list of references 3) and " bioactive glass treatment gingivitis, dental hemorrhage and the effect of removing the odontoseisis symptom " (patent No. CN 1562075) (list of references 4) report that all bioactivity glass is by 40~60%SiO
2, 10~30%CaO, 10~35%Na
2O, 2~8%P
2O
5, 0~10%B
2O
3, 0~8%K
2O, 0~5%MgO process through high-temperature fusion; Bioactivity glass can induce the bone mineralising to form mutually; Can on dental surface, induce the overglaze formation of new tooth, thereby reach the position that is corroded of sealing dentinal tubule, remedying tooth, reach desensitization and prevent the effect of tooth in solitude.Bioactivity glass can promote the damaged healing of growth, the bone of osseous tissue can promote the growth of soft tissue to heal again, and the surface activity of bioactivity glass can promote the generation of somatomedin, procreation, the activating cell gene expression (list of references 5,6) of promotion cell.Like this, bioactivity glass has therapeutical effect to common dental such as gingivitis, dental hemorrhage and odontoseisiss.
But clinical practice has shown that a lot of patients feel stimulation pain in the direct applied zone of bioactivity glass, even interrupts or be difficult to treat.This is to react and cause that local pH surge (reaching 12) causes because accelerated surface takes place when contact with liquid bioactive glass particle.Reduce pH, alleviate the stimulation pain of tooth and gingiva, need new bioactivity glass to form.
List of references 1: " OCCLUSION OF DENTIN TUBULES BY 45S5
" LITKOWSKI; HACK; SHEAFFER ANDGREENSPAN; BIOCERAMICS Vol.10,411-414,1997
List of references 2:P.Stoor; E.
and J.I.Salonen; " Antibacterial effects of a bioactive glass paste on oralmicroorganisms; " AGTA Odontol.Scand.56,161-165,1998
List of references 3: " bioactive glass compositions and the Therapeutic Method that uses bioactivity glass ", Chinese patent numbers 97193085
List of references 4: " bioactive glass treatment gingivitis, dental hemorrhage and the effect of removing the odontoseisis symptom " Chinese patent CN 1562075
List of references 5:I.D.Xynos, A.J.Edgar, L.D.K.Buttery; L.L.Hench; J.M.Polak, " Gene-expression profiling of humanosteoblasts following treatment with the ionic products ofBioglass 45S 5dissolution, " J.Biomed.Mater.Res.; 55:151-157,2001
List of references 6:L.L.Hench, I.D.Xynos, A.J.Edgar, L.D.K.Buttery, J.M.Polak, Zhong Jipin, Liu Xuanyong, Chang Jiang, " Gene Activating Glasses, " Journal of Inorganic Materials, the 17th volume, the 5th phase, 897-909,2002
Summary of the invention
The present invention is directed to the problems referred to above and a kind of pH buffer activity glass is provided, this pH buffer activity glass can cushion pure bioactive glass (SiO
2, CaO, Na
2O, P
2O
5, B
2O
3) particle surface reaction causes that local pH increases sharply (for example, reaching 12), thereby eliminate and the stimulation pain when alleviating patient treatment, reach therapeutic effect.
The technical scheme that the present invention takes is:
1) a kind of pH buffer activity glass, said pH buffer activity glass comprises following composition A or following composition B:
Form A:
SiO
2-40~60%;CaO-10~30%;
Na
2O-10~30%;P
2O
5-2~8%;
B
2O
3-0~10%; Solid acid granule-0.5~5.0%;
Form B:
SiO
2-3~20%;CaO-0.5~2.5%;
Na
2O-0.5~2.5%;P
2O
5-0.1~0.5%;
B
2O
3-0~0.1%; Glycerol, Polyethylene Glycol and resin-75~95%;
Wherein, the content ratio of said glycerol, Polyethylene Glycol and resin is: 75 (± 5): 24.5 (± 1.5): 0.5 (± 0.1).
2), it is characterized in that said solid acid granule is for being selected from solid citric acid granule (C according to the 1st described pH buffer activity glass
6H
8O
7) and titania based solid acid particles (SO
4 2-/ TiO
2) at least a.
3), it is characterized in that said resin is for being selected from carbomer (C according to the 1st described pH buffer activity glass
3H
4O
2) and epoxy resin is at least a.
4) according to each described pH buffer activity glass of 1-3, it is characterized in that the content ratio of said glycerol, Polyethylene Glycol and resin is: 75: 24.5: 0.5.
5), it is characterized in that said composition A is a powder according to the 4th described pH buffer activity glass.
6), it is characterized in that said composition B is a unguentum according to the 4th described pH buffer activity glass.
7) according to the 5th described pH buffer activity glass, the particle diameter that it is characterized in that said pH buffer activity glass is less than 20 μ m.
PH buffer activity glass of the present invention can cushion pure bioactive glass (SiO
2, CaO, Na
2O, P
2O
5, B
2O
3) particle surface reaction causes that local pH increases sharply (reaching 12), thereby eliminate and the stimulation pain when alleviating patient treatment, reach therapeutic effect.Simultaneously, it is stable in depositing and transporting that these form the packing back, can keep biological activity and keep therapeutic effect.
The invention still further relates to a kind of method for preparing of the pH of preparation buffer activity glass, it may further comprise the steps:
1) with the SiO of said proportioning
2, CaO, Na
2O, P
2O
5, B
2O
3High-temperature fusion forms bioactivity glass;
2) with the bioactivity glass of above-mentioned acquisition solid acid granule (forming A) with said proportioning, or glycerol, Polyethylene Glycol and resin (forming B) come uniform mixing and said pH buffer activity glass.
The invention still further relates to the purposes of a kind of pH buffer activity glass at the medicine of preparation control gingivitis, dental hemorrhage, dentin hypersensitiveness.
Description of drawings
Fig. 1 is the figure of the technique effect (comparing the influence that composition A and B change pH with matched group) of pH buffer activity glass among the demonstration embodiment 1.
The specific embodiment
Below will describe the specific embodiment of the present invention in detail with reference to embodiment, dated especially as not having, content ratio among the application or percentage composition are all in mass.
The mechanism of action that bioactivity glass can be treated gingivitis, dental hemorrhage and dentin hypersensitiveness's symptom derives from its biological activity.At first be the sodium ion (Na in the bioactive glass particle
+) with mouthful liquid in hydrion (H
+) ion-exchange reactions takes place, cause the bioactive glass particle surface to generate a Si-rich phase (Si-OH), Si-rich phase will attract calcium (Ga
2+) and phosphorus (PO
4-) ion or ionic group stockpile the generation hydroxyapatite layer bioactive glass surface and dental surface, i.e. the mineralising phase of tooth, sealing dentinal tubule reaches the effect of tooth desensitization; A large amount of sodium ion from bioactive glass particle, discharge and mouthful liquid in the hydrion exchange get into and cause in the bioactive glass particle that local pH increases, thereby can reach the effect of antibacterial and treatment gingivitis and dental hemorrhage.Therefore, local pH can be up to 12 moment.
The present invention relates to a kind of pH buffer activity glass, said pH buffer activity glass comprises SiO
2, CaO, Na
2O, P
2O
5, B
2O
3And the formation bioactivity glass, on this basis, the present invention also comprises solid acid granule (forming A) in addition.Be that bioactive glass particle is directly used at present.But, clinical practice shown a lot of patients feel to stimulate in the zone that applies with moment acute painful, even interruption or be difficult to treat.This is because accelerated surface taking place when contact with liquid like the said bioactive glass particle of preceding mechanism reacts, and causes that local pH surge (reaching 12) causes.In forming A, the introducing of a spot of solid acid particulate component can provide and replenish hydrion (H in mouthful liquid
+) lose; Like this can efficient buffer partial pH gather and increase; With control moment pH 9.5 below eliminating and to alleviate patient's stimulation pain, while solid acid granule provide the supplemental hydrogen ion can accelerate enduringly again with bioactivity glass in the ion-exchange reactions of sodium ion, like this; The particulate introducing of solid acid does not only reduce the biological activity of bioactivity glass; Gather and increase cushioning partial pH, can also promote the biological activity reaction when alleviating patient's stimulation pain, guarantee therapeutic effect.
Wherein, in above-mentioned pH buffer activity glass, said solid acid granule can be the solid acid granule that has no side effect commonly used, because this composition is applied to the oral cavity, therefore is preferably solid citric acid granule (C
6H
8O
7) or titania based solid acid particles (SO
4 2-/ TiO
2), most preferably be the solid citric acid granule.In addition, form A and be preferably powder form.The patient requires speed fast and effective when treat stomatological hospital and clinic.The micron particle specific surface area is big, and response speed is fast, can not can on the affected part makes the patient feel stimulation pain and the fast and effective therapeutic effect of acquisition speed as directly being coated in less than 20 μ m in micron bioactive glass particle powder.In the case, possibly form the suitable professional oral cavity doctor of A uses to patient treatment.In use, preferably with said bioactivity glass less than 20 μ m granule powder with directly be coated on the affected part less than the solid acid granulometric composition A of 20 μ m.
In addition, pH buffer activity glass of the present invention can also comprise from 75% to 95% glycerol, Polyethylene Glycol and resin (forming B) in addition on the basis of bioactivity glass.And, in the process of reaction, reach therapeutical effect because fast reaction can take place for bioactivity glass and aqueous solution.But process with the form of aqueous solution like fruit product, when behind production, storing and transporting, bioactive glass particle can be given birth to reaction with waterishlogging, will lose therapeutic effect after the reaction.Form B and mix with bioactive glass particle, can keep the biological activity and the therapeutic effect of bioactivity glass with water-free glycerol, Polyethylene Glycol and resin.Simultaneously; Macromolecule polyethylene glycol and resin can be adsorbed on biological active granulated surface; Although these macromolecules can dissolve away the disengaging particle surface very soon in water; Also just in this tens second the buffer granule in aqueous solution like the said surface reaction of preceding mechanism, thereby buffer pH gathers and increases, and can not feel in the time of can making patient treatment that moment is acute painful.
Wherein, in above-mentioned pH buffer activity glass, said resin can be the resin that has no side effect commonly used, because this composition is applied to the oral cavity, can be preferably carbomer (C
3H
4O
2) or epoxy resin, most preferably be carbomer.The content ratio of said glycerol, Polyethylene Glycol and resin is preferably: 75: 24.5: 0.5.Said composition B is preferably the unguentum form, and this is because the patient is carried out steadiness and family therapy, and the unguentum teeth brushing way that the bioactivity glass micron particle is prepared into is used for the best and convenient.
Above-mentioned pH buffer activity glass has the treatment to oral disease such as gingivitis, dental hemorrhage and dentin hypersensitiveness etc., and, can not stimulate dental tissue to cause having a toothache bitterly.The specialty doctor has powder property that the patient is carried out the fast treatment of curative effect, and the patient has the stable long-term steadiness family therapy of unguentum use carrying out.
Embodiment
Preparation embodiment
With the first five component high-temperature fusion of content shown in the following table 1, glycerol, Polyethylene Glycol and the resin of content come uniform mixing and obtain pH buffer activity glass of the present invention shown in the solid acid granule of content shown in the reuse following table 1 or the following table 2.
Table 1
Constituent content |
Preparation example 1 |
Preparation example 2 |
Preparation example 3 |
Preparation example 4 |
Preparation example 5 |
Preparation example 6 |
SiO
2 |
40 |
50 |
60 |
40 |
50 |
60 |
CaO |
30 |
20 |
10 |
30 |
20 |
10 |
Na
2O
|
20 |
30 |
10 |
20 |
30 |
10 |
P
2O
5 |
5 |
2 |
8 |
5 |
2 |
8 |
B
2O
3 |
0 |
10 |
5 |
0 |
10 |
5 |
The solid citric acid granule |
5 |
0.5 |
3.0 |
0 |
2.0 |
0 |
Titania based solid acid particles |
0 |
0 |
0 |
5 |
0.5 |
0.5 |
[0047]Table 2
Constituent content |
Preparation example 7 |
Preparation example 8 |
Preparation example 9 |
Preparation example 10 |
Preparation example 11 |
Preparation example 12 |
SiO
2 |
3 |
11 |
20 |
3 |
11 |
20 |
CaO |
2.5 |
1.5 |
0.5 |
2.5 |
1.5 |
0.5 |
Na
2O
|
0.5 |
2.5 |
1.5 |
0.5 |
2.5 |
1.5 |
P
2O
5 |
0.1 |
0.5 |
0.3 |
0.1 |
0.5 |
0.3 |
B
2O
3 |
0.1 |
0 |
0.05 |
0.1 |
0 |
0.05 |
Glycerol |
64 |
76 |
52.5 |
64 |
76 |
52.5 |
Polyethylene Glycol |
17.25 |
21 |
24.7 |
17.25 |
21 |
24.7 |
Carbomer |
0.57 |
0.44 |
0.3 |
0 |
0 |
0.10 |
Epoxy resin |
0 |
0 |
0 |
0.57 |
0.50 |
0.3 |
The experiment of effect example 1-pH buffering
Matched group: bioactivity glass (45%SiO
2, 24.5%CaO
2, 24.5%Na
2O, 6%P
2O
5) (<20 microns): 100%
Forming A forms: bioactivity glass 95%, 5% citric acid granule (specifically consists of: 42.75%SiO
2, 23.28%CaO, 23.27%Na
2O, 5.70%P
2O
5, 5.00% citric acid granule)
Forming B forms: bioactivity glass 7.5%, glycerol, Polyethylene Glycol and carbomer 92.5% (glycerol, Polyethylene Glycol and carbomer ratio are 75: 24.5: 0.5) (specifically consist of: 3.38%SiO
2, 1.84%CaO, 1.83%Na
2O, 0.45%P
2O
5, 69.38% glycerol, 22.66% Polyethylene Glycol, 0.46% carbomer)
Take by weighing each 0.77g of weight of three groups respectively, put into the little plastic containers that fill the 2ml deionized water respectively, stirred for 5 seconds, then, after 10 seconds, measure its pH respectively with the pH appearance.Following table 3 has shown the effect that the pH buffer activity glass of the matched group of above composition, the pH buffer activity glass of forming A and composition B produces with accompanying drawing 1 in the experiment of pH buffering.
Table 3
? |
Matched group |
Form A |
Form B |
Amount of samples (g) |
0.77 |
0.77 |
0.77 |
Water consumption (ml) |
2 |
2 |
2 |
PH (after 15 seconds) |
12.02 |
9.22 |
8.6 |
Effect example 2
* * the do clinical research contrast experiment of anti-gingival hemorrhage with commodity toothpaste on composition B unguentum among the embodiment one and use one market; Experimental group (forming the B unguentum) 47 people, matched group (commodity toothpaste) 48 people, 34.5 years old mean age; Standard deviation: experimental group 8.8 years old, matched group 10.1 years old.
Table 4 is listed all experimenters (95 people) that accomplish test after gingival hemorrhage is estimated, mean that the gingival hemorrhage index is kept the score and standard deviation (SD).Experimental group and matched group gingival hemorrhage index there was no significant difference before the experiment.The gingival hemorrhage index standard of keeping the score is: the 0=gingiva is not hemorrhage; The 1=petechial hemorrhage; The 2=streak-like hemorrhage; The 3=lamellar is hemorrhage; The 4=hematostaxis, or mobile hemorrhage.After six weeks, test group gingival hemorrhage index obviously reduces.After six weeks, test group gingival hemorrhage index is reduced to 58.8%, and matched group gingival hemorrhage index is less than 14%.The concrete contrast situation that gingival hemorrhage index (standard deviation) is kept the score sees the following form 4.
Table 4
Effect example 3
* * have dentin hypersensitiveness symptom, air-breathing or when eating cold drink tooth can feel pain.Composition B unguentum with depositing among the embodiment one after 2 years was brushed teeth two days, sooner or later each once, each more than 1 minute after, allergic symptom alleviates greatly.
* * have dental hemorrhage symptom is brushed teeth or local tooth can be hemorrhage when flipping.Composition B unguentum with depositing among the embodiment one after 2 years is brushed teeth three days times, sooner or later each once, each more than 1 minute after, hemorrhage disappearance.