CN115245566B - Application of mesoporous silicon-loaded nitrogen-doped graphene nanocomposite in preparation of photo-thermal periodontitis treatment drug and preparation method - Google Patents
Application of mesoporous silicon-loaded nitrogen-doped graphene nanocomposite in preparation of photo-thermal periodontitis treatment drug and preparation method Download PDFInfo
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- 239000002114 nanocomposite Substances 0.000 title claims abstract description 61
- 229910052710 silicon Inorganic materials 0.000 title claims abstract description 47
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 title claims abstract description 44
- 239000010703 silicon Substances 0.000 title claims abstract description 44
- 201000001245 periodontitis Diseases 0.000 title claims abstract description 28
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- 229910021389 graphene Inorganic materials 0.000 title claims abstract description 26
- 239000003814 drug Substances 0.000 title claims abstract description 20
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- 238000011282 treatment Methods 0.000 title abstract description 15
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- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 abstract description 11
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- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- 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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6923—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Abstract
The application of mesoporous silicon loaded nitrogen-doped graphene nanocomposite in preparation of medicines for treating periodontitis by light and heat and the preparation method thereof are characterized in that mesoporous silicon nanospheres are synthesized firstly, then the mesoporous silicon nanospheres are used for loading nitrogen-doped graphene quantum dots, and chlorhexidine is fixed on MSN@NGQDs nanocomposite to obtain an MSN@NGQDs-CHX nanocomposite system, and the prepared nanocomposite system has good water phase dispersibility and can be directly injected into periodontitis parts to slowly permeate into deep dental sockets. Then, the illumination treatment is applied to the lesion part, and the pathogenic bacteria are killed by the heat generated by the unique photo-thermal conversion performance of the nanocomposite, so that the nanocomposite has an ultra-large specific surface area, and a good drug slow release effect can be realized, so that a small dosage of chlorine can be slowly released, and the antibacterial effect is further continuously exerted after photo-thermal treatment, and the pathogenic bacteria in deep tissues are thoroughly eradicated.
Description
Technical Field
The invention relates to the technical field of periodontitis treatment, in particular to application and a preparation method of a mesoporous silicon-loaded nitrogen-doped graphene nanocomposite in preparation of a photo-thermal periodontitis treatment drug.
Background
Chronic periodontitis is a chronic inflammatory disease characterized clinically by plaque biofilm as an initiating factor and periodontal tissue destruction, and is a main cause of loss of teeth in adults, and pain is a main oral disease which endangers the health of human teeth and the whole body. If gingivitis is not treated in time, the inflammation may spread from the gums deep into periodontal ligament, alveolar bone and cementum, and develop into periodontitis. The early stage is easy to ignore because of no obvious subjective symptoms, and the symptoms are serious when the symptoms are still present, and even the teeth cannot be reserved. In China, the incidence rate of periodontitis exceeds 50%, and the incidence rate of people aged 60-74 is more high up to 70-90%. The global economic burden due to periodontitis is about 4.16 billion dollars each year and will increase year by year as the population grows and life expectancy per capita increases. Traditional clinical treatment of periodontitis mainly uses special instruments to remove plaque biofilm, so as to remove plaque and control infection. However, due to the complex anatomy of periodontal, periodontal pathogens are hidden in the bifurcation or deep pocket to form a biofilm, and bacteria are easy to re-colonize, which is difficult to thoroughly remove. Although the combination treatment of antibiotics can better improve the bacterial inhibition rate, the problem of drug resistance caused by repeatedly overdosing the antibiotics can lead periodontal tissues to chronically infect for a long time, and inflammation repeatedly attacks, thus affecting the normal life of patients. Mechanical intervention can have a more negative impact on periodontal tissue regeneration. The use of antibiotics at high concentrations also brings side effects such as liver and kidney injury, oral and digestive tract dysbacteriosis, etc.
In the existing treatment of periodontitis, the pure photothermal therapy is limited by the complexity of periodontal anatomy, the size of laser light spots and the penetration depth of near infrared light, so that deep residual bacteria cannot be thoroughly eradicated.
Disclosure of Invention
In order to solve the defects and shortcomings of periodontitis treatment in the current oral clinic, the invention provides application and a preparation method of a mesoporous silicon-loaded nitrogen-doped graphene nanocomposite in preparation of a photo-thermal periodontitis treatment drug.
The technical scheme adopted by the invention is as follows: the application of the mesoporous silicon-loaded nitrogen-doped graphene nanocomposite in preparing a medicament for treating periodontitis by light and heat is characterized in that the mesoporous silicon-loaded nitrogen-doped graphene nanocomposite is prepared from mesoporous silicon @ nitrogen-doped graphene materials (MSN@NGQDs) and pi-pi stacking effect loaded Chlorhexidine (CHX) by a physical electrostatic adsorption method.
The Chlorhexidine (CHX) is chlorhexidine acetate.
The mesoporous silicon loaded nitrogen doped graphene nanocomposite mesoporous silicon@nitrogen doped graphene materials (MSN@NGQDs) are spherical or ellipsoidal, wherein the diameter of mesoporous silicon is 100-200 nm, and the nitrogen doped graphene quantum dots are accumulated in the mesopores of the mesoporous silicon materials.
The concentration of the mesoporous silicon loaded nitrogen-doped graphene nanocomposite in the medicament for treating periodontitis by light and heat is 200 mu g/mL.
The medicine for treating periodontitis by light and heat is excited under 808 and nm near infrared condition, and the power is 1.5W/cm 2 。
The preparation method of the mesoporous silicon-loaded nitrogen-doped graphene nanocomposite comprises the following steps:
(1) Mesoporous Silicon Nanospheres (MSNs) are prepared by a template method: reacting 0.3-1. 1 g hexadecyl trimethyl ammonium bromide (CTAB) aqueous solution with 2M NaOH at 60-80 ℃ for 30 min, then adding 2.5-10 mL TEOS (TEOS) at a titration rate of 30-90 mu L/min to stir 2 h, washing and centrifuging by deionized water and ethanol, mixing the mixture with ammonium nitrate in absolute ethanol according to a mass ratio of 2:5-5:2, and continuously stirring 6-24 h at 60 ℃ to obtain the mesoporous silicon nanosphere material;
(2) Synthesizing carboxylated nitrogen-doped graphene quantum dots (NGQDs) by a hydrothermal method: rapidly mixing 20-100 mg citric acid solution with 800-1200 μl ammonia water, transferring into autoclave lining, reacting at 200deg.C for 1-6 h, naturally cooling to room temperature, and dialyzing the product with cellulose dialysis bag 72 h;
(3) Synthesizing the MSN@NGQDs nanocomposite by an amide method: mixing 30-100 mg mesoporous silicon nano material and 0.5-2.0 mL APTES, stirring for 6-24 h to obtain an amino mesoporous silicon nanosphere, activating nitrogen-doped graphene quantum dots rich in carboxyl groups by EDC and NHS for 30 min, and finally mixing the activated carboxylated nitrogen-doped quantum dots with the amino mesoporous silicon for 10-20 h at 4 ℃ to obtain the MSN@NGQDs nano composite material;
(4) Preparing MSN@NGQDs-CHX nanocomposite: stirring 10 mg/mL MSN@NGQDs and 1.0-10 mg/mL chlorhexidine acetate (CHX) at room temperature for 24 h, and centrifugally cleaning to obtain the MSN@NGQDs-CHX nanocomposite.
The molecular weight cut-off of the cellulose dialysis bag in the step (2) is 100-500 Da.
A medicament for treating periodontitis by light and heat comprises a mesoporous silicon-loaded nitrogen-doped graphene nanocomposite (MSN@NGQDs-CHX), wherein the mesoporous silicon-loaded nitrogen-doped graphene nanocomposite is prepared by loading Chlorhexidine (CHX) on a mesoporous silicon@nitrogen-doped graphene material (MSN@NGQDs) through a physical electrostatic adsorption method and pi-pi stacking effect.
The beneficial effects of the invention are as follows: the invention provides an application of mesoporous silicon loaded nitrogen-doped graphene nanocomposite in preparation of a medicament for treating periodontitis by light and heat and a preparation method thereof. Then, the illumination treatment is applied to the lesion part, and the pathogenic bacteria are killed by the heat generated by the unique photo-thermal conversion performance of the nanocomposite, so that the nanocomposite has an ultra-large specific surface area, and a good drug slow release effect can be realized, so that a small dosage of chlorine can be slowly released, and the antibacterial effect is further continuously exerted after photo-thermal treatment, and the pathogenic bacteria in deep tissues are thoroughly eradicated.
Drawings
FIG. 1 (a) is a technical scheme for preparing the MSN@NGQDs-CHX nanocomposite system according to the invention, and (b) is a schematic diagram of the nanocomposite system constructed according to the invention in periodontitis treatment.
Fig. 2 is a transmission electron microscope image of (a) mesoporous silicon, (b) nitrogen-doped graphene, and (c) mesoporous silicon-loaded nitrogen-doped graphene nanocomposite, respectively.
FIG. 3 is a graph showing the photothermal temperature rise of the prepared MSN@NGQDs nanocomposite at (a) different concentrations and (b) different near infrared light radiation powers, respectively.
FIG. 4 shows the inhibitory effect of the inventive MSN@NGQDs-CHX nanocomposite system against methicillin-resistant Staphylococcus aureus. "NIR-" is a group to which near infrared light is not applied, and "NIR+" is a group to which 1.5W/cm is applied 2 808 nm near infrared light irradiation of (2) for 10 min treatment groups.
FIG. 5 is a graph showing the results of the inventive MSN@NGQDs-CHX nanocomposite system after various days of treatment of skin abscess areas of mice imitating periodontal abscess.
Detailed Description
The invention will be further described with reference to the accompanying drawings and the following embodiments, it being understood that the drawings and the following embodiments are only for illustrating the invention, not for limiting the invention.
Example 1 template method for preparing Mesoporous Silicon Nanospheres (MSN)
0.3-1 g hexadecyl trimethyl ammonium bromide (Cetyltrimethylammonium Bromide, CTAB) aqueous solution reacts with 2M NaOH with different volumes respectively for 30 min at different temperatures (60-80 ℃), TEOS (2.5-10 mL) is added with different titration speeds (30-90 mu L/min) for stirring for 2 h, deionized water and ethanol are used for washing and centrifuging, and then the mixture and ammonium nitrate are mixed with absolute ethanol according to mass ratios (2:5, 1:1 and 5:2) respectively, and are continuously stirred for different times (6-24 h) at 60 ℃ to obtain the proper mesoporous silicon nanosphere material.
Example 2 hydrothermal Synthesis of carboxylated Nitrogen doped graphene Quantum dots (NGQDs)
Mixing 20-100 mg citric acid solution with ammonia water of different volumes (800, 1000, 1200 μl), transferring into an autoclave liner of 50 mL polytetrafluoroethylene, reacting at 200deg.C for different times (1, 3, 6 h), naturally cooling to room temperature, and dialyzing the product with cellulose dialysis bag (molecular weight cut-off 100-500 Da) for 72 h.
EXAMPLE 3 amide Synthesis of MSN@NGQDs nanocomposite
30-100 mg mesoporous silicon nano material and APTES with different volumes (0.5-2.0 mL) are mixed and stirred for different times (6-24 h) to obtain the aminated mesoporous silicon nanospheres. And activating the nitrogen-doped graphene quantum dots rich in carboxyl by EDC and NHS for 30 min, and finally mixing the activated carboxylated nitrogen-doped graphene quantum dots with the aminated mesoporous silicon at 4 ℃ for reaction of 10-20 h to obtain the MSN@NGQDs nanocomposite.
Example 4 preparation of MSN@NGQDs-CHX nanocomposite System by physical Electrostatic adsorption of Chlorhexidine by mesoporous Structure and pi-pi stacking between Large pi bond on graphene Quantum dot and Chlorhexidine aromatic Ring
10 mg/mL MSN@NGQDs were stirred with chlorhexidine acetate (CHX) at various concentrations (1.0-10 mg/mL) at room temperature for 24 h. And (3) obtaining the MSN@NGQDs-CHX nano composite system through centrifugal cleaning.
Experimental results
As can be seen from fig. 1, the mesoporous silicon nanospheres are synthesized first and then used for loading the nitrogen-doped graphene quantum dots. And then fixing chlorhexidine on the MSN@NGQDs nanocomposite to obtain the MSN@NGQDs-CHX nanocomposite system. The prepared nano composite system has better water phase dispersibility, can be directly injected into periodontitis parts, and can slowly permeate into deep tooth sockets. Then, the pathological change part is irradiated with light, and heat is generated to kill pathogenic bacteria through the unique light-heat conversion performance of the nano composite material. The nanocomposite has an ultra-large specific surface area, can realize good drug slow release effect, and can enable small dosage of chlorine to be slowly released, so that after introduction of photothermal treatment, bacteriostasis is further continuously exerted, and pathogenic bacteria in deep tissues are thoroughly eradicated.
As can be seen from FIG. 2, the mesoporous silicon prepared by the invention is in a porous nanosphere structure, and after the graphene quantum dots are deposited, the mesoporous silicon becomes a spherical or ellipsoidal MSN@NGQDs nanocomposite. The mesoporous silicon has a diameter of about 100-200 nm, and the nitrogen-doped graphene quantum dots can be effectively accumulated in the mesopores of the mesoporous silicon material.
As can be seen from FIG. 3, the photo-thermal heating curves of the MSN@NGQDs nanocomposite materials with different concentrations under the excitation of near infrared (808, nm) with different powersIs significantly different. The invention adopts the power of 1.5W/cm 2 The nanocomposite material concentration is 200 mug/mL, the irradiation time is 10 min as the optimal treatment condition, and the final temperature can exceed 50 ℃.
As can be seen from FIG. 4, the MSN@NGQDs-CHX nanocomposite system synthesized by the invention has a remarkable antibacterial effect. When MSN@NGQDs are simply used, the nanocomposite material does not show obvious antibacterial effect. After the MSN@NGQDs nanocomposite group is irradiated by near infrared light, the antibacterial effect is effectively enhanced, and the bacterial survival rate is reduced to about 60%. After the MSN@NGQDs-CHX nano composite system is irradiated by near infrared light, the antibacterial effect is obviously enhanced, and 100% of bacteria are killed after 6 h.
From fig. 5, it can be seen that the msn@ngqds-CHX nanocomposite system synthesized by the invention is applied to a mouse skin abscess model imitating periodontal abscess, and exhibits excellent therapeutic effects after near infrared light irradiation. The control and nanomaterial-free illuminated groups did not heal at 15 days, and the tissue under the scab was ulcerated and the inflammatory response was severe. Compared with a control group, the recovery condition of the MSN@NGQDs nanocomposite illumination group is obviously improved, so that the nanocomposite has good photo-thermal performance, and a certain degree of inhibition on pathogenic bacteria is realized, but a small wound can still be seen in 15 days, so that pathogenic bacteria residues still exist. After the MSN@NGQDs-CHX nano composite system is subjected to photo-thermal treatment, the inflammation condition is well controlled on the 7 th day, and no wound or inflammation residue is observed on the 15 th day after treatment, so that the nano composite system synthesized by the invention can efficiently inhibit periodontitis pathogenic bacteria and effectively treat periodontitis lesions.
In conclusion, the MSN@NGQDs-CHX nano composite system provided by the invention has excellent photo-thermal antibacterial effect under near infrared light excitation, can realize 100% inhibition rate on drug-resistant staphylococcus aureus under the enhancement of a small amount of drugs, and has good biocompatibility and small toxic and side effects. The material has the advantages of simple preparation method, good biocompatibility, high-efficiency photo-thermal/photo-dynamic/drug synergistic antibacterial capability under near infrared light radiation, capability of effectively killing common gram-positive pathogenic bacteria of periodontitis, namely drug-resistant staphylococcus aureus, small local dosage, small side effect, no influence on healthy periodontal tissues of the oral cavity, high safety, capability of promoting healing of periodontal infection areas in a short period, high safety, small side effect and the like.
The skilled person will know: while the invention has been described in terms of the foregoing embodiments, the inventive concepts are not limited to the invention, and any modifications that use the inventive concepts are intended to be within the scope of the appended claims.
The above description is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above examples, and all technical solutions belonging to the concept of the present invention belong to the protection scope of the present invention. It should be noted that modifications and adaptations to the present invention may occur to one skilled in the art without departing from the principles of the present invention and are intended to be within the scope of the present invention.
Claims (4)
1. The application of the mesoporous silicon-loaded nitrogen-doped graphene nanocomposite in preparing a medicament for treating periodontitis by photothermal therapy is characterized in that the mesoporous silicon-loaded nitrogen-doped graphene nanocomposite is prepared from mesoporous silicon @ nitrogen-doped graphene materials (MSN@NGQDs) and pi-pi stacking effect-loaded chlorhexidine acetate (CHX) by a physical electrostatic adsorption method, the concentration of the mesoporous silicon-loaded nitrogen-doped graphene nanocomposite in the medicament for treating periodontitis is 200 mug/mL, and the medicament for treating periodontitis by photothermal therapy is excited under the near infrared condition of 808 nm, wherein the power is 1.5W/cm 2 。
2. The use of claim 1, wherein the mesoporous silicon supported nitrogen doped graphene nanocomposite mesoporous silicon @ nitrogen doped graphene materials (msn @ ngqds) are spherical or ellipsoidal, wherein the mesoporous silicon diameter is 100-200 nm, and the nitrogen doped graphene quantum dots accumulate in the mesopores of the mesoporous silicon material.
3. A method for preparing the mesoporous silicon-supported nitrogen-doped graphene nanocomposite material according to claim 1, comprising the following steps:
(1) Mesoporous Silicon Nanospheres (MSNs) are prepared by a template method: reacting 0.3-1. 1 g hexadecyl trimethyl ammonium bromide (CTAB) aqueous solution with 2M NaOH at 60-80 ℃ for 30 min, then adding 2.5-10 mL TEOS (TEOS) at a titration rate of 30-90 mu L/min to stir 2 h, washing and centrifuging by deionized water and ethanol, mixing the mixture with ammonium nitrate in absolute ethanol according to a mass ratio of 2:5-5:2, and continuously stirring 6-24 h at 60 ℃ to obtain the mesoporous silicon nanosphere material;
(2) Synthesizing carboxylated nitrogen-doped graphene quantum dots (NGQDs) by a hydrothermal method: rapidly mixing 20-100 mg citric acid solution with 800-1200 μl ammonia water, transferring into autoclave lining, reacting at 200deg.C for 1-6 h, naturally cooling to room temperature, and dialyzing the product with cellulose dialysis bag 72 h;
(3) Synthesizing the MSN@NGQDs nanocomposite by an amide method: mixing 30-100 mg mesoporous silicon nano material and 0.5-2.0 mL APTES, stirring for 6-24 h to obtain an amino mesoporous silicon nanosphere, activating nitrogen-doped graphene quantum dots rich in carboxyl groups by EDC and NHS for 30 min, and finally mixing the activated carboxylated nitrogen-doped quantum dots with the amino mesoporous silicon for 10-20 h at 4 ℃ to obtain the MSN@NGQDs nano composite material;
(4) Preparing MSN@NGQDs-CHX nanocomposite: stirring 10 mg/mL MSN@NGQDs and 1.0-10 mg/mL chlorhexidine acetate (CHX) at room temperature for 24 h, and centrifugally cleaning to obtain the MSN@NGQDs-CHX nanocomposite.
4. The method according to claim 3, wherein the cellulose dialysis bag in the step (2) has a molecular weight cut-off of 100 to 500 and Da.
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| CN103655207A (en) * | 2013-12-04 | 2014-03-26 | 上海纳米技术及应用国家工程研究中心有限公司 | Drug-loaded mesoporous-silica-reinforced dental binder and preparation method thereof |
| WO2022077037A1 (en) * | 2020-10-13 | 2022-04-21 | Mana Health Technologies Gmbh | Irradiation device and system for photodynamic disinfection of teeth and gums |
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| CN103655207A (en) * | 2013-12-04 | 2014-03-26 | 上海纳米技术及应用国家工程研究中心有限公司 | Drug-loaded mesoporous-silica-reinforced dental binder and preparation method thereof |
| WO2022077037A1 (en) * | 2020-10-13 | 2022-04-21 | Mana Health Technologies Gmbh | Irradiation device and system for photodynamic disinfection of teeth and gums |
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