Oral care composition for inhibiting porphyromonas gingivalis and preparation method thereof

Abstract

The invention provides an oral care composition for inhibiting porphyromonas gingivalis and a preparation method of the oral care composition, and relates to two complementary oral care formulas (formula I: basic protection type; formula II: targeted therapy type) comprises: a) Formula I: 15% of hydrated silica, 30% of calcium carbonate, 0.1% of cetylpyridinium chloride, and 0.3% of stannous fluoride, and the RDA value is less than or equal to 80; the formula II comprises 20% of fully-hydrated silicon dioxide, 0.3% of lactoferrin and 0.1% of Angiopep-2 liposome, the RDA value of the formula II is smaller than or equal to 50, the blood brain barrier penetration rate of the formula II is larger than or equal to 15%, the wall thickness of ethyl cellulose of the propolis micro-capsule of the formula I is 2.0-2.5 micrometers, the 3D micro-capsule of the formula II comprises a pH response layer, a mineralization layer and a freeze-drying inner core, and the process of the formula I is that 50 nm zinc oxide and silicon oxide are coated into a ZnO / SiO core-shell structure. According to the invention, colonization and dissemination of the porphyromonas gingivalis (Pg) are inhibited through a triplex mechanism of friction injury control, biofilm penetration and system immune activation, and an industrial preparation process of the porphyromonas gingivalis (Pg) is disclosed.

Description

Technical Field

[0001] The present invention relates to the technical field of traction brackets, in particular to an oral care composition for inhibiting Porphyromonas gingivalis and a preparation method thereof. Background Art

[0002] The hierarchical requirements for the prevention and treatment of Pg bacteria are as follows: 1. Primary protection: Healthy people need to prevent Pg colonization (plaque control RDA ≤ 80); 2. Precision treatment: Periodontitis patients need to eliminate drug-resistant strains (MIC ≤ 0.1 μg / mL) and block systemic spread (such as breaking through the blood-brain barrier).

[0003] The existing technologies have the following technical defects: a single formula cannot take into account both mechanical cleaning strength (RDA) and the stability of bioactive ingredients (such as phage enzyme inactivation); traditional sustained-release technologies (such as liposomes) cannot achieve time-controlled release of multiple components (reason for modification: to supplement that liposomes can only achieve sustained release of a single component and cannot adapt to multi-phase release requirements).

[0004] Therefore, it is necessary to provide a new oral care composition for inhibiting Porphyromonas gingivalis and a preparation method thereof to solve the above technical problems. Summary of the Invention

[0005] The purpose of the present invention is to solve the shortcomings of the prior art and to propose an oral care composition for inhibiting Porphyromonas gingivalis and a preparation method thereof.

[0006] In order to achieve the above object, the present invention adopts the following technical solutions, including: a new formula design, wherein formula I (basic protective type):

[0007] 1. Components and functions: Reduce RDA to 78±3 (ISO 11609:2017); calcium carbonate (30%): specific surface area (BET) 12m 2 / g, improving cleaning efficiency by 30%; glycerol (20%): water activity (aw) 0.85, inhibiting Pg extracellular polysaccharide synthesis (AEPS = -45%); xylitol (5%): inhibiting Pg glycolysis and acid production (ΔpH = 0.32, p < 0.01); cocamidopropyl betaine (1%): critical micelle concentration (CMC) 0.15%, surface tension 28 mN / m (better than SLS); cetylpyridinium chloride (CPC, 0.1%): synergistic index CI with stannous fluoride = 0.83 (Chou-Talalay model); stannous fluoride (0.3%): forming SnF complex, destroying the Pg outer membrane potential (Zeta potential +15 mV→-5 mV).

[0008] 2. Technical core: Zinc oxide pre-dispersion: 50nm silicon oxide coated zinc oxide (ZnO / SiO core-shell structure, TEM verification), lecithin adsorption capacity 0.2mg / m2 (Langmuir model fitting), storage stability> 24 months (accelerated test 40℃ / 75%RH); propolis microencapsulation: ethyl cellulose (EC) wall material thickness 2.1μm (SEM measurement), 72-hour cumulative release rate 86.5% (Higuchi model R 2 =0.992).

[0009] Formula II (targeted therapy):

[0010] 1. Components and functions: Fully hydrated silica (20%): spheroidized (D50 = 5 μm), RDA value 48 ± 2; calcium hydrogen phosphate (15%): porosity 62% (mercury intrusion method), 40% increase in Pg bacteria adsorption efficiency; ultrapure glycerol (18%): osmotic pressure 145 mOsm / kg (isotonic with saliva); xylitol (8%): ​​inhibits Pg metabolism through the PPP pathway (ΔNADPH = -35%); lactoferrin (0.3%): chelates Fe with stannous fluoride 3+ , down-regulating Pg HmuR gene expression by 78% (qRT-PCR); Angiopep-2 liposomes (0.1%): particle size 85 nm, blood-brain barrier translocation efficiency 17.3% (hCMEC / D3 model); phage lytic enzyme (0.02%): specific activity 1.2×10 5 U / mg, and the clearance rate of drug-resistant strains (ermF+) was 99.99%.

[0011] 2. Core technology: 3D microcapsule compartmentation: Microfluidic technology is used to prepare three-layer microcapsules: outer layer: pH-responsive chitosan (dissolution threshold pH = 5.5); middle layer: calcium phosphate mineralization layer (Ca / P = 1.67, XRD verification); inner core: trehalose freeze-dried lyase (activity retention rate 98.7%); cold-pressed filling: molding pressure 0.5 MPa at -20°C, lyase secondary structure retention rate (CD spectrum) ≥ 95%.

[0012] Compared with the prior art, the advantages and positive effects of the present invention are:

[0013] 1. Dual-system tiered design: covers both prevention (formulation I) and treatment (formulation II) scenarios, with clear clinical transitional use plans (e.g., I for prevention and II for acute phase).

[0014] 2. Multi-mechanism synergy: integrating the triple effects of friction damage control, biomembrane penetration and immune activation.

[0015] 3. Industrial adaptability: Solve the stability problem of active ingredients through pre-dispersion, microencapsulation and cold pressing processes. DETAILED DESCRIPTION

[0016] In order to more clearly understand the above-mentioned objects, features and advantages of the present invention, the present invention is further described below in conjunction with the embodiments. It should be noted that, in the absence of conflict, the embodiments of the present application and the features therein can be combined with each other.

[0017] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways than those described herein. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0018] Example 1. The present invention provides an oral care composition for inhibiting Porphyromonas gingivalis and a preparation method thereof, comprising the following steps: preparing a composition according to formula I: ball-milling zinc oxide nanoparticles (50 nm) and lecithin (mass ratio 1:0.2) in ethanol for 2 hours, spray-drying to obtain a pre-dispersed powder; emulsifying a propolis ethanol solution with EC (core material ratio 1:3) and spray-drying to obtain microcapsules with an encapsulation efficiency of 91%; mixing the components according to the formula ratio, homogenizing them using a three-screw extruder (temperature 50°C, speed 200 rpm), and filling to obtain the finished product.

[0019] Example 2: Cold Pressing Process Verification of Formulation II: A three-layer microcapsule was prepared using a microfluidic chip (inner diameter 200 μm), and premixed with the remaining ingredients after freeze-drying. The microcapsules were molded at a pressure of 0.5 MPa in a nitrogen environment at -20°C. The lytic enzyme activity test showed an initial activity of 1.2×10 6 U / mg, activity after filling 1.18×10 6 U / mg (retention rate 98.3%).

[0020]

[0021]

[0022] Example 3: Verification of blood-brain barrier translocation to establish a Pg intracranial infection mouse model (ICR system); Group treated with Formulation II: Pg load in brain tissue 3.2×10 3 CFU / g (qPCR); control group: 6.8×10 5 CFU / g (p<0.001).

[0023]

[0024]

[0025] The above description is merely a preferred embodiment of the present invention and does not constitute any other form of limitation to the present invention. Any person skilled in the art may utilize the technical contents disclosed above to change or modify them into equivalent embodiments with equivalent changes for application in other fields. However, any simple modification, equivalent change, and modification of the above embodiments made in accordance with the technical essence of the present invention without departing from the technical solution of the present invention shall still fall within the scope of protection of the technical solution of the present invention.

Claims

1. An oral care composition for inhibiting Porphyromonas gingivalis, characterized in that: include: a) Formula I: contains 15% hydrated silicon dioxide, 30% calcium carbonate, 0.1% cetylpyridinium chloride, and 0.3% stannous fluoride, with an RDA value ≤ 80; b) Formula II: contains 20% fully hydrated silicon dioxide, 0.3% lactoferrin, and 0.1% Angiopep-2 liposomes, with an RDA value ≤ 50 and a blood-brain barrier penetration rate ≥ 15%.

2. The oral care composition for inhibiting Porphyromonas gingivalis according to claim 1, characterized in that: The ethylcellulose wall thickness of the propolis microcapsules in formula I is 2.0-2.5 μm, and the 3D microcapsules in formula II include a pH-responsive layer, a mineralized layer, and a freeze-dried core.

3. A method for preparing an oral care composition for inhibiting Porphyromonas gingivalis, comprising: The process of the formulation I is as follows: 50 nm zinc oxide is coated with silicon oxide to form a ZnO / SiO core-shell structure, lecithin is added at a ratio of 1:0.2, and ball milled for 2 hours, and spray dried to obtain a pre-dispersed powder; The process of the formula II is as follows: the three-layer microcapsules containing the bacteriophage lytic enzyme are mixed with other ingredients at -20°C and nitrogen, and then cold-pressed at 0.5 MPa to form the microcapsules.

4. The method for preparing the oral care composition for inhibiting Porphyromonas gingivalis according to claim 3, wherein: The biosafety and compliance are divided into toxicology data and regulatory compliance, of which the toxicology data is acute oral toxicity: LD 50 >5000mg / kg; Eye irritation test does not cause reversible inflammation or irreversible damage: completely non-irritating; Regulatory compliance: Total fluoride concentration ≤0.15%; CPC concentration ≤0.1%.

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