KR-20260068124-A - DETECTION AND TREATMENT OF CARIES AND MICROCAVITIES WITH NANOPARTICLES

Abstract

A component, such as a nanoparticle, is provided for detecting and/or treating one or more active caries lesions or microcavities on a subject's tooth. This component or nanoparticle contains a biocompatible and biodegradable polymer having at least one cationic region and/or a net positive charge, so as to associate with one or more active and/or early caries lesions on the tooth in the subject's oral cavity. The component or nanoparticle is, in some cases, water-soluble or water-dispersible. Additionally, the component or nanoparticle contains an imaging agent (e.g., a fluorescent dye or a dye) bound to the biocompatible and biodegradable polymer. Thus, the component or nanoparticle may indicate the presence of one or more active caries lesions to which the component or nanoparticle associates. An oral hygiene composition containing such a compound/nanoparticle and a method for preparing and using the same are also provided.

Inventors

• 라한, 조르그
• 창, 시웨-렌
• 클락슨, 브라이언
• 존스, 나단 에이
• 크자즈카-자쿠보우스카, 아가타

Assignees

• 더 리젠츠 오브 더 유니버시티 오브 미시건
• 포즈난 유니버시티 오브 메디컬 사이언시스

Dates

Publication Date

20260513

Application Date

20161021

Priority Date

20151021

Claims (20)

1. A step of functionalizing starch nanoparticles containing a -CH₂CHOHCH₂N =( CH₃ ) ₃ group corresponding to at least one cation region into a reactive group capable of reacting with an imaging agent; and The method comprises the step of reacting the reactive group on the starch nanoparticle with the imaging agent comprising a CONH-fluorescein group or a Cy5 group, and A method for preparing an oral administration composition in which the above starch nanoparticles further comprise an oral hygiene active ingredient containing fluorine.
2. In paragraph 1, A method for preparing an oral administration composition, further comprising the step of reacting the starch nanoparticles with a cationic moiety to form at least one cationic region prior to the above functionalization.
3. In paragraph 1, A method for preparing a composition for oral administration, further comprising the step of functionalizing the starch nanoparticles to have at least one first reactive group capable of reacting with the cation moiety before reacting with the cation moiety.
4. A method for preparing an oral administration composition according to claim 1, wherein the starch nanoparticles comprise hydroxyl groups.
5. A method for preparing an oral administration composition according to claim 1, wherein the starch nanoparticles comprise a polymer containing glucose repeating units.
6. A biocompatible and biodegradable starch polymer having at least one cationic region capable of associating with one or more carious lesions on a tooth in the oral cavity of a subject; and Nanoparticles comprising a fluorescent imaging agent that is bonded to the above biocompatible and biodegradable starch polymer and can indicate the presence of one or more caries lesions when the nanoparticles associate with one or more caries lesions.
7. In paragraph 6, Nanoparticle comprising a cationic moiety in which at least one cationic region is combined with a biocompatible and biodegradable starch polymer.
8. In paragraph 6, Nanoparticles in which the above-mentioned cation moiety comprises a tertiary amine or a quaternary amine.
9. In paragraph 8, Nanoparticles that are reaction products of glycidyl trimethylammonium chloride, wherein the above-mentioned cation moiety is bonded to the above-mentioned biocompatible and biodegradable starch polymer.
10. In paragraph 6, The above-mentioned fluorescent imaging agent is a nanoparticle containing a fluorescent group that exhibits fluorescence in response to electromagnetic rays derived from a dental treatment lamp.
11. In Paragraph 10, The above-mentioned fluorescent imaging agent is a nanoparticle comprising at least one biocompatible dye.
12. In paragraph 6, The above nanoparticles are nanoparticles that can be detected by visual inspection of the oral cavity.
13. In Paragraph 12, The above visual investigation involves nanoparticles using an optical filter.
14. In paragraph 6, The above nanoparticles have a zeta potential of about 0 mV or more to about +50 mV or less at pH 7.
15. In paragraph 6, Zwitterionic nanoparticles.
16. In paragraph 6, Nanoparticles having an average diameter of about 10 nm or more to about 1,000 nm or less.
17. In paragraph 6, Nanoparticles containing additional oral hygiene active ingredients.
18. In Paragraph 17, The above-mentioned oral hygiene active ingredient is a nanoparticle selected from the group consisting of caries inhibitors, remineralizing agents, antibacterial agents, anti-tartar agents, and combinations thereof.
19. In Paragraph 18, The above oral hygiene active ingredient comprises a fluoride-containing component present in an amount of about 0.02 weight% or more to about 2.2 weight% or less after being incorporated into the nanoparticle, and The above-mentioned fluoride-containing component is a nanoparticle selected from the group consisting of fluorohydroxyapatite, stannous fluoride, sodium fluoride, calcium fluoride, silver fluoride dehydrate, sodium monofluorophosphate, difluorosilane, and combinations thereof.
20. In Paragraph 17, Nanoparticles comprising a calcium-containing component present in an amount of about 1% by weight or more to about 5% by weight or less after the above oral hygiene active component is incorporated into the nanoparticles.

Description

Detection and Treatment of Caries and Microcavities with Nanoparticles The present invention relates to nanoparticles having a diagnostic agent that can be delivered to the oral cavity of a subject to detect caries and/or therapeutically treat caries, particularly active (progressive) carious lesions. Reference explanation regarding related applications This application claims priority to U.S. Provisional Application No. 62/244,512 filed on October 21, 2015. The full specification of this Provisional Application is incorporated herein by reference. This section provides background information related to the present invention, which is not necessarily prior art. Dental caries is the most common dental disease globally. In the United States, over 90% of adults have experienced cavities in their permanent teeth. Approximately 36% of the world's population has active cavities. Furthermore, as developed countries increasingly adopt high-sugar diets, the frequency of tooth decay is likely to increase. Dental caries forms when bacteria in the dental biofilm ferment sugars on the tooth surface and produce acid, causing demineralization of the dentin and/or enamel. Early demineralization manifests as white spot lesions forming on the surface enamel. These lesions, referred to as "microcavities" or early caries lesions, can be restored through a process called remineralization, which utilizes calcium and phosphorus from saliva and aids from the presence of fluoride in drinking water and toothpaste. However, if demineralization continues, irreversible cavitation occurs, requiring dental procedures to stop the demineralization. Although early-stage caries can still be restored through improved oral hygiene, they are difficult to diagnose, and tactile methods carry the potential to cause permanent damage to the teeth. For example, early caries (white spot lesions) can be restored through improved oral hygiene and the application of fluoride; however, demineralization weakens the teeth and causes cavitation, requiring tooth restoration. Therefore, the diagnosis and treatment of early caries lesions can reduce the need for more complex and costly dental treatments. However, white spot lesions are not easy to diagnose because their presence is highly variable. Typically, the diagnosis of dental caries is performed optically and tactilely using mirrors and probes; however, optical detection can be difficult, and tactile probing of carious lesions can accelerate cavitation. To identify cavities, particularly those in the interdental areas (interproximal caries), X-ray imaging of the teeth is commonly performed. While this method can clearly confirm the progression of cavity to facilitate treatment, it has several drawbacks. First, X-ray imaging cannot identify early-stage lesions that can still be restored through improved oral hygiene practices and the application of active ingredients (e.g., fluoride application). Additionally, X-rays are expensive for both dentists and patients. Furthermore, radiation exposure from X-rays is associated with a risk of cancer, which consequently underscores the need to minimize the necessity of radiation-based diagnostics. The drawings described herein are for the purpose of illustrating selected embodiments only, are not all possible embodiments, and are not intended to limit the scope of the invention. FIG. 1 illustrates a chemical reaction scheme for preparing starch nanoparticles according to specific variations of the present invention. Unmodified nanoparticles (1) are cationized to become cationic particles (2). TEMPO oxidation of cationic particles (2) and unmodified particles (1) produces amphoteric particles (3) and anionic particles (5), respectively. EDC/NHS chemistry with fluorescein amine is performed on particles (3) and (5) to produce fluorescently labeled cationic particles (4) and fluorescently labeled anionic particles (6). FIG. 2 shows the FTIR spectra of unmodified (1), cation (2), anion (5), and amphoteric (3) starch nanoparticles described in the context of FIG. 1. Corresponding regions for the CH and C=O peaks are highlighted. FIGS. 3A and B. FIG. 3A is a chart summarizing the particle size and zeta potential results for modified starch nanoparticles (StNPs). Size was measured by intensity-weighted dynamic light scattering and number-weighted nanoparticle trace analysis. FIG. 3B is a chart summarizing the starch degradation results of unmodified (1), amphoteric (3), and fluorescent cationic (4) starch nanoparticles. The iodine vertical lines represent the measurements of red intensity, which decrease from the initial state to the final state upon exposure to saliva, indicating starch degradation. The Benedict reaction was measured by comparing absorbance values at 575 nm; absorbance increases after degradation by saliva, suggesting the presence of reducing sugars (p<0.005 for all final vs. initial value comparisons). Figures 4A and 4B illustrate the starch degradation