WO2021121393A1 - Revêtement antibactérien et minéralisant sur des surfaces dentaires pour la prévention des caries dentaires - Google Patents
Revêtement antibactérien et minéralisant sur des surfaces dentaires pour la prévention des caries dentaires Download PDFInfo
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- WO2021121393A1 WO2021121393A1 PCT/CN2020/137637 CN2020137637W WO2021121393A1 WO 2021121393 A1 WO2021121393 A1 WO 2021121393A1 CN 2020137637 W CN2020137637 W CN 2020137637W WO 2021121393 A1 WO2021121393 A1 WO 2021121393A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
- C07K14/4723—Cationic antimicrobial peptides, e.g. defensins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
Definitions
- Dental caries is one of the leading public health problems threatening human health reported by World Health Organization. More than 2.5 billion people are burdened with untreated caries which directly affect their quality of life.
- the oral environment contains a unique and diverse subset of microflora.
- Dental caries is partly a consequence of a microbial shift from healthy to pathogenic/acid-producing strains such as Streptococcus mutans (S. mutans) and Lactobacilli. Their colonization of the tooth surface leads to the formation of dental plaque biofilm, which in turn initiates the demineralization of dental hard tissue, and results in tissue degradation.
- Dental caries is also a dynamic process of interspersing demineralization and remineralization. Demineralization, favoring cavity formation, is reversible given adequate time between acidogenic challenges for remineralization to occur. Therefore, strategies for caries prevention primarily focus on two fields (1) inhibiting dental plaque formation, and (2) inducing remineralization of dental hard tissue and reducing its demineralization.
- Antimicrobial peptides act as a natural host-defense system. They possess a broad-spectrum of antimicrobial activities, and carry limited side effects and bacterial resistance to the host. Histatin 5 (H5) , a salivary AMP, derived naturally from the human parotid and submandibular glands, destroys a broad range of fungi and bacteria, including S. mutans. H5 as a component of the acquired enamel pellicle (AEP) shows the ability to adsorb onto enamel surface and actively suppresses enamel demineralization. This provides ample evidence that H5 may be a candidate as an anti-biofouling agent against dental caries. However, in order to design a bi-functional bioactive molecule with anti-biofouling and mineralizing properties, H5 needs further modification to induce remineralization.
- Phosphoserine is the key moiety among them that binds with hydroxyapatite (HA) and attracts free calcium ions (Ca 2+ ) to serve as a nucleus to initiate mineralization.
- Sp residue is often applied in tooth and bone regeneration studies for promoting and mediating mineralization process.
- tooth coatings for dental products, such as oral care compositions, any of which containing a suitable amount of phosphoserine-histatin 5 to prevent micro-organisms adhesion on teeth and/or restore the decayed tooth surfaces.
- Fig. 1 depicts the chemical structure of molecules. a. Sp-H5. b. H5.
- Fig. 2 depicts an HPLC chromatogram of Sp-H5 and H5 at 214 nm.
- Fig. 3 depicts a MS spectrum of Sp-H5 and H5. a. Sp-H5. b. H5.
- Fig. 4 depicts susceptibility assay of S. mutans (ATCC 35668) in the BHI, Sp-H5, H5 and CHX, respectively.
- a The absorbance of all groups (BHI, BHI+S. mutans, BHI+S. mutans+Sp-H5, BHI+S. mutans+H5, BHI+S. mutans+CHX) in different concentrations. Compared with the absorbance of BHI, the absorbance of Sp-H5 or H5 dropped and there was no significant difference in the concentration 2 ⁇ mol/ml (*) , while there was no significant difference absorbance of CHX in the concentration 0.25 ⁇ mol/ml (*) . #means that the absorbance of those groups firstly emerged 90%reduction comparing with that of the BHI+S. mutans group.
- b The MIC and MBC of Sp-H5, H5 and CHX were listed.
- Fig. 5 depicts fluorescent images by CLSM and viability count of S. mutans biofilms on tooth enamel surfaces.
- a The image of S. mutans biofilms in the BHI group (drug-free) .
- b, c, d, e The images of S. mutans biofilms in the Sp-H5 groups with different concentrations (4 ⁇ MIC, 8 ⁇ MIC, 16 ⁇ MIC and 32 ⁇ MIC, respectively) .
- f, g, h, i The images of S. mutans biofilms in the Sp-H5 groups with different concentrations (4 ⁇ MIC, 8 ⁇ MIC, 16 ⁇ MIC and 32 ⁇ MIC, respectively) .
- Fig. 6 depicts fluorescent images by CLSM and viability count of S. mutans on the Sp-H5 and H5 coated tooth enamel surfaces.
- a The image of S. mutans biofilms in the BHI group (drug-free) .
- b, c, d, e The images of S. mutans biofilms in the Sp-H5-2MIC, Sp-H5-4MIC, Sp-H5-8MIC and Sp-H5-16MIC groups, respectively.
- f g, h, i, The images of S. mutans biofilms in the H5-2MIC, H5-4MIC, H5-8MIC and H5-16MIC groups, respectively.
- j Viable count of S. mutans on the peptides coated enamel surfaces after 5 h incubation. *P ⁇ 0.05, compared with BHI.
- Fig. 7 depicts the mineral loss of enamel surfaces in the demineralization solutions by ICP-OES. Ca/P loss amount of enamel surfaces in the demineralization solutions after peptides coating. Blue bar means Ca loss and orange bar means P loss. Different capital letters show significant differences (A ⁇ B ⁇ C, D ⁇ E ⁇ F, P ⁇ 0.05) .
- Fig. 8 depicts the mineral gain of enamel surfaces in remineralization solutions for 24 h by ICP-OES and remineralization micrographs by FE-SEM.
- a Ca/P gain amount of enamel surfaces in the remineralization solutions after peptides coating.
- Blue bar means Ca gain and orange bar means P gain.
- Different capital letters show significant differences (A>B, D>E, P ⁇ 0.05) .
- f, g, h SEM micrographs of remineralization cross section in Sp-H5, H5 and control group ( ⁇ 20000) .
- the white dash line displays the interface of remineralization.
- i, j, k Reduced SEM micrographs of f, g, h, respectively ( ⁇ 10000) .
- Fig. 9 depicts a cytocompatibility evaluation of Sp-H5 using HGF-1.
- a Proliferation of HGF-1 treated with Sp-H5 and H5 at different concentrations for 4 h by the MTT assay.
- b Proliferation of HGF-1 on enamel surfaces treated with 16 ⁇ MIC Sp-H5, H5 and sterile deionized water for 3 days by the MTT assay.
- c, d, e SEM micrographs of HGF-1 on the enamel surface treated with 16 ⁇ MIC Sp-H5, H5 and sterile deionized water for 3 days, respectively ( ⁇ 200) .
- f Amplified micrograph of c ( ⁇ 1000) .
- Fig. 10 depicts the side view (a1) and top view (a2) of Sp-H5 adsorption onto HA by MD simulation.
- Fig. 11 depicts the average binding energy of peptide-HA complexes in the demineralization system by MD simulation.
- Fig. 12 depicts the average binding energy of peptide-HA complexes in the remineralization system by MD simulation.
- Fig. 13 depicts the schematic diagram of Sp-H5 in this invention.
- Sp-H5 adheres to enamel surface.
- Sp-H5 kills planktonic S. mutans.
- Sp-H5 inhibits S. mutans adhesion on it.
- enamel surface is protected against demineralization.
- the thickness of the regenerated crystal layer increases.
- Fig. 14 depicts the MD graphs in the demineralization system.
- a The side view of Sp-H5-HA.
- b The top view of Sp-H5-HA.
- c The side view of H5-HA.
- d The top view of H5-HA.
- Fig. 15 depicts the MD graphs in the remineralization system.
- a The side view of Sp-H5-HA.
- b The top view of Sp-H5-HA.
- c The side view of H5-HA.
- d The top view of H5-HA.
- Fig. 16 depicts a HPLC chromatograms of Sp-H5 (4 umol/mL) incubated in human saliva at 37 °C at different time point.
- RT1 and RT 3 represented saliva.
- RT 2 represented Sp-H5.
- Fig. 17 depicts a HPLC chromatograms of H5 (4 umol/mL) incubated in human saliva at 37 °C at different time point.
- RT1 and RT 3 represented saliva.
- RT 2 represented H5.
- Fig. 18 depicts a removable palate plate model. Tooth slices were fixed onto the removable plastic palate plate. Perforated tinfoil was used to cover tooth slices.
- Fig. 19 depicts 3D graphs of biofilms in Sp-H5 (a) , H5 (b) , and control group (c) , respectively.
- Green color means live biofilm.
- Micro-organisms are easy to accumulate on tooth surfaces producing local low pH environment which causes demineralization of tooth hard tissues. Preventing micro-organisms adhesion and restoring the decayed tooth surfaces are equally important. A novel coating with dual bioactive property is therefore described herein that can both simultaneously prevent micro-organisms adhesion on teeth and restore the decayed tooth surfaces. After coating tooth surfaces, micro-organisms are difficult to adhere on the coated tooth surfaces, and new crystals are regenerated more and easier on the decayed tooth surface in the re-mineralization environment.
- the coating prevents/reduces bacterial adhesion and restores early dental decay by regenerating a new remineralization layer.
- the coating chemical is a modified from an endogenous antimicrobial peptide histatin 5 (H5) , such as phosphoserine-histatin 5 (Sp-H5) . After modifying, the antibacterial ability is not affected.
- Sp-H5 showed a high binding affinity to tooth surface, strong suppression to acid corrosion, and promotion on new regenerated crystals. Sp-H5 is safe for human beings. Because of dual bioactive properties, Sp-H5 can be used as a protective coating by direct varnishing or adding into toothpastes/mouthwashes.
- An oral health product containing Sp-H5 contains a suitable amount of phosphoserine-histatin 5 to prevent micro-organisms adhesion on teeth and/or restore the decayed tooth surfaces.
- the oral health product contains from 0.01%to 25%by weight of Sp-H5.
- the oral health product contains from 0.1%to 10%by weight of Sp-H5.
- the oral health product contains from 0.5%to 5%by weight of Sp-H5.
- a revolutionary strategy for preventing and treating dental caries via constructing an anti-biofouling and mineralizing bioactive layer on tooth surface, for resisting dental plaque formation and simultaneously realizing self-healing remineralization.
- a bi-functional bioactive molecule phosphoserine-histatin 5 (Sp-H5) with anti-biofouling and mineralizing properties is designed by grafting the Sp moiety onto the N-terminus of H5 to achieve remineralization ability.
- Remineralization of tooth enamel involves supplying calcium and phosphate ions from a remineralizing agent to the tooth structure to restore mineral ions in a demineralized enamel.
- remineralizing agents include one or more of calcium phosphate, amorphous calcium fluoride phosphate, calcium chloride, monopotassium phosphate, and sodium fluoride.
- An oral health product optionally contains a suitable amount of a remineralizing agent to restore the decayed or damaged tooth surfaces.
- the oral health product contains from 0.01%to 25%by weight of remineralizing agent.
- the oral health product contains from 0.1%to 10%by weight of remineralizing agent.
- the oral health product contains from 0.5%to 5%by weight of remineralizing agent.
- adsorption capacity with HA particles of Sp-H5 by the Micro BCA method is more than H5.
- Sp-H5 is affinity with HA particles. It realizes the first step of the dual bioactive molecule to adsorb onto tooth surface.
- adsorption time with enamel of Sp-H5 is in the first 5 min. Adsorption reaction is very fast, that is in a matter of seconds.
- Sp-H5 has anti-planktonic bacterial ability.
- the minimal inhibitory concentration (MIC) of Sp-H5 is 2 ⁇ mol/mL, and the minimal bactericidal concentration (MBC) of Sp-H5 is 4 ⁇ mol/mL.
- Sp-H5 has anti-biofilm activity. Viability counts are significantly dropped from 16 ⁇ MIC of Sp-H5.
- Sp-H5 has anti-bacterial adhesion ability. Viability counts are significantly dropped from 2 ⁇ MIC of Sp-H5.
- Sp-H5 has stronger ability to inhibit demineralization of tooth hard tissue than no coating group.
- Sp-H5 has stronger ability to promote remineralization of demineralized tooth hard tissue than no coating group.
- Sp-H5 is safe for human gingival fibroblasts (HGF-1) .
- adsorption capacity with HA particles of Sp-H5 by the Micro BCA method is more than H5.
- Sp-H5 is affinity with HA particles.
- the first step of the dual bioactive molecule is to adsorb onto tooth surface.
- the ability of affinity with HA will help Sp-H5 stably and continually remain onto the enamel surface.
- adsorption time with enamel of Sp-H5 is in the first 5 min. As shown in Table 2, adsorption reaction is very fast.
- Sp-H5 is a synthesized peptide with stable properties.
- Sp-H5 is a modified multi-functional peptide from human salivary antimicrobial peptide H5.
- Sp-H5 is made by the phosphorylation of the alcohol functional group in at least one of the serine residues of H5 to produce phosphoserine-histatin or Sp-H5.
- the serine adjacent the N-terminal of H5 is phosphorylated.
- Sp-H5 can readily adsorb onto the tooth surface fast and stably.
- Sp-H5 can inhibit and/or reduce planktonic bacteria, bacterial biofilm, and bacterial adhesion.
- Sp-H5 can be used on teeth before eating, and even in a low pH environment, Sp-H5 still remains adsorbed on teeth surface and can protect teeth from acid injury (inhibition of demineralization) .
- a figure or a parameter from one range may be combined with another figure or a parameter from a different range for the same characteristic to generate a numerical range.
- S. mutans ATCC 35668, ATCC, Manassas
- S. mutans were cultured in Horse Blood Medium under anaerobic (85%N 2 , 10%H 2 , and 5%CO 2 ) conditions at 37 °C.
- Cells were harvested by centrifugation (5000 rpm, 10 min) , washed once with 10 mM sodium phosphate-buffered saline (PBS, pH 7.2) , and resuspended in brain-heart infusion broth (BHI, Difco Laboratories, Detroit) at a concentration of 106 CFU/mL.
- PBS sodium phosphate-buffered saline
- BHI brain-heart infusion broth
- Tooth slices 3 ⁇ 3 ⁇ 1.5 mm 3 (number: 73) and 5 ⁇ 4 ⁇ 1.5 mm 3 (number: 48) ) were prepared by a water-cooled diamond saw (IsoMet low-speed saw, Buehler, Lake Bluff, IL) .
- One working surface of complete enamel tissue was determined from each tooth slice by MicroCT Skyscan 1172 (Bruker MicroCT, Kontich, Belgium) . The enamel working side of the tooth slice was then polished and the other sides were marked with acid-proof nail polish. All tooth slices were cleaned and stored in deionized water at 4 °C.
- working reagent working reagent were prepared using the Pierce BCA Protein Assay Kit (Rockford, IL) .
- Working reagents 100 ⁇ L/well) were added to a 96-well plate, followed by standard solutions (100 ⁇ L/well) and peptide solutions (100 ⁇ L/well) .
- the plate was incubated for 30 min in the dark, and the absorbance (562 nm) was measured using a plate reader.
- the concentration (C) of the BSA standard solution had a linear relationship with the bsorbance (A) at 562 nm.
- a function of C a ⁇ A + b was determined (a and b are constants) .
- the final concentration (the peptide solution mixed with HA) (C f ) and the initial concentration (the peptide solution without HA) (C 0 ) were computed by the function using the absorbance data of the peptide solution mixed with (A f ) and without (A 0 ) HA.
- the minimal inhibitory concentration (MIC) was defined as the lowest concentration of peptide that caused at least a 90%reduction in absorbance compared with the negative control group.
- the minimal bactericidal concentration (MBC) was defined as the lowest concentration of peptide resulting in no colony formation on agar plates after incubation. Ten icroliters of cell suspension from each well was plated on a horse blood agar plate and incubated at 37 °C for 48 h. All determinations were conducted in triplicate experiments.
- One selected randomly tooth slice in each group was stained using the LIVE/DEAD BacLight Bacterial Viability Kit (L7012, Thermo Fisher Scientific, Waltham) in the dark for 30 min. Fluorescence images were obtained using confocal laser scanning microscopy (CLSM, Fluoview 1000, Olympus) . Another tooth slice in each group was used for colony-forming unit (CFU) counting. These tooth slices were placed in 1000 ⁇ L of BHI solution, and adherent biofilms were removed from the enamel surfaces by sonication for 30 s. Ten-fold serial dilutions of the suspensions were plated in duplicate on horse blood agar. After a 48 h incubation, CFU was counted. Three independent biofilm experiments were performed.
- HGF-1 Viability Assay.
- Human gingival fibroblasts HGF-1, Otwo Biotech Inc., Shen Zhen, China
- HGF-1 fibroblasts were incubated in Dulbecco’s Modified Eagle’s Medium (GIBCO, Grand Island) ontaining 10%fetal bovine serum (GIBCO, Grand Island) and 1%enicillin-streptomycin (GIBCO, Grand Island) .
- HA makes up the primary composition of the enamel, it was used to reveal the reaction mechanism between peptides and the enamel in the MD simulation.
- Three systems were constructed using the software GROMACS 5.0.4: 6, 7 (1) peptide adsorption onto the HA system, (2) peptide-HA complexes in the demineralization system, and (3) peptide-HA complexes in the remineralization system. Peptide structures were simulated by Swiss-PdbViewer. 8 The molecular structure and parameters of HA were obtained from the literature.
- Human saliva was collected from a volunteer in the morning prior to oral cleaning. The collected saliva samples were centrifuged at 12,000 rpm for 20 min. The supernatant was collected and filtered through the 0.45 mm membrane filter to remove any debris. Peptide (Sp-H5 or H5) was added into the human saliva to achieve the final concentration 4 umol/ml. The saliva with peptide was incubated at 37 °C. At 0, 20, 40 and 120 min, 40 uL solutions were taken from each sample. The samples were analyzed by high performance liquid chromatography (HPLC) . Total run time of HPLC-UV (214 nm) analysis was 21 min and the injection volume was set at 10 ⁇ L.
- HPLC high performance liquid chromatography
- Tooth slices were removed and stained by the LIVE/DEAD BacLight Bacterial Viability Kit (Kits, L7012) for 30 min in the dark. Confocal laser scanning microscopy was used for qualitative characterization of biofilms. 3D graphs of biofilms were analyzed.
- Using one-way ANOVA a significant decrease in concentration was observed from 0 to 5 min in the Sp-H5 solution (P ⁇ 0.05) . There was no significant difference in concentration at 5, 20, 40, and 60 min. The vast majority of adsorption reactions between Sp-H5 and the enamel occurred within the first 5 min.
- the susceptibility assay for planktonic S. mutans in BHI, Sp-H5, H5, and CHX is summarized in Figure 4.
- the MIC of Sp-H5 was 2 ⁇ mol/mL.
- the MBC of Sp-H5 was 4 ⁇ mol/mL.
- the CLSM images of 16 ⁇ MIC and 32 ⁇ MIC of Sp-H5 showed that the majority of S. mutans were dead (red, Figure 5d) .
- the majority of S. mutans in BHI were alive (green, Figure 5a) .
- S. mutans is a gram-positive bacterium with a cell wall consisting of lipoteichoic acids and peptidoglycan.
- H5 is a positively charged AMP that is able to interact with the peptidoglycan layer and anionic teichoic acids of S. mutans.
- 10 Peptide P-113 is the shortest fragment of H5, and it was found that two cationic lysine residues Lys2 and Lys10 in peptide P-113 were essential for cell membrane permeability and interactions with intracellular structures. 11 ⁇ 13 Cationic amino acid residues such as Lys, histidine (His) , and arginine (Arg) may be important for Sp-H5 induction of cell death by binding to cell wall, enhancing membrane permeability, and interacting with intracellular DNA of S. mutans.
- FIG. 10a, b shows stable and unique molecule conformations (top view and side view) of Sp-H5 and H5 adsorption onto HA at 100 ns, respectively. From the binding energy results, at the initial simulation time stage ( ⁇ 5 ns) , both Sp-H5 and H5 were immediately adsorbed onto the surface of HA ( Figure 10c1, d1) . During adsorption progression, both Sp-H5 and H5 experienced a conformational change from a helical to an unwinding loop structure. After reaching equilibrant adsorption, Sp-H5 adsorbed to HA vertically, while H5 adsorbed horizontally. Sp of Sp-H5 was pushed against the surface of HA ( Figure 10a1) .
- Figure 10c1, d1 shows the binding energies of Sp-H5-HA and H5-HA in the adsorption system.
- the black and red curves represent the evaluation of van der Walls and electrostatic forces, respectively.
- the horizontally sustained black curve indicates no van der Walls forces in the adsorption system.
- the red curve dropped at onset and reached an equilibrium after 5 ns, demonstrating the existence of electrostatic force in the adsorption system. Electrostatic interactions were the main driving force in the adsorption system.
- Figure 10c2, d2 shows the binding energy between HA and different amino acid residues in Sp-H5 and H5, respectively.
- positively charged amino acid residues Lys 12 , Lys 14 and Lys 18 , Arg 13 , and Arg 23 in Sp-H5 show stronger electrostatic interactions with HA.
- Figure 10d2 apart from Lys 12 , Arg 13 , Lys 14 , and Lys 18 , positively charged amino acid residues Lys6 and His4 and the negatively charged amino acid residue aspartic residue (Asp 2 ) also participated in the adsorption of H5 onto HA. These positively charged amino acid residues were the main functional components of the peptide that contributed to the adsorption onto HA.
- Figure 10c3, d3 shows the binding energy between key constituents of HA and Sp-H5 and H5, respectively.
- the black curve initially rose, representing repulsive forces between the peptide and Ca 2+ of HA.
- the blue curve decreased at the initial simulation time ( ⁇ 20 ns) , representing the presence of attraction forces between the peptide and PO 4 3- of HA.
- PO 4 3- was the main functional component in HA that contributed to the adsorption with peptide.
- the adsorption mechanism between Sp-H5 and HA consisted of the interaction of the positively charged amino acid residues Lys 12 , Lys 14 , Lys 18 , Arg 13 , and Arg 23 in Sp-H5 with PO 4 3- in HA.
- H5 or S p -H5 played an important role as a protective layer to effectively isolate HA from Ace - /PO 4 3- .
- Sp-H5-HA and H5-HA showed different average binding energies with ions in the demineralization solution.
- H5-HA complex H5-HA, Ace - : -260 kJ/mol; PO 4 3- : -225 kJ/mol
- the average binding energy of Ace - /PO 4 3- and HA of the Sp-H5-HA complex Sp-H5-HA, Ace - : -250 kJ/mol; PO 4 3- : -170 kJ/mol
- the average binding energy of Ca 2+ and HA of the HA-Sp-H5 complex decreased more (H5-HA: -235 kJ/mol; Sp-H5-HA: -356 kJ/mol) .
- Sp-H5 In the demineralization environment (pH 4.5) , Sp-H5 possessed more negative charges than H5 because of the presence of Sp. Due to the greater number of negative charges of Sp-H5, the electrostatic repulsive forces between the Sp-H5-HA complex and acid radical ions in the demineralization environment were stronger than those between the H5-HA complex and acid radical ions. Sp played a key role in decreasing the reaction between acid radical ions and HA in the Sp-H5-HA complex. In summary, due to the presence of Sp, Sp-H5 presented a stronger ability to inhibit demineralization than H5.
- Figure 12 shows the verage binding energy between the peptide-HA complex and ions (Ca 2+ and PO 4 3- ) in remineralization solution. It was observed that HA of the peptide-HA complex reacted with Ca 2+ and PO 4 3- , while peptide of the peptide-HA complex only reacted with Ca 2+ .
- Sp-H5 provided five major advantages. (1) Sp-H5 could adhere to the enamel surface through the electrostatic attraction forces of positively charged amino acid residues (Lys 12 , Arg 13 , Lys 14 , Lys 18 , and Arg 23 ) of Sp-H5 with negatively charged PO 4 3- of HA. (2) Sp-H5 could kill planktonic S. mutans and S. mutans biofilm. (3) Coating of Sp-H5 on the enamel could inhibit the adhesion of S. mutans.
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Abstract
La présente invention concerne un revêtement dentaire ayant des propriétés bioactives doubles qui peut à la fois empêcher l'adhérence de micro-organismes sur les dents et réparer les surfaces de dents cariées, le revêtement contenant de la phosphosérine-histatine 5.
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US20170291930A1 (en) * | 2016-04-11 | 2017-10-12 | University Of Maryland, Baltimore | Histatin-5 Based Synthetic Peptides and Uses Thereof |
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