Functionalized antimicrobial particles

Abstract

Provided herein are antimicrobial particles comprising an organic or inorganic core, at least one antimicrobially active unit and at least one polymerizable unit, both covalently attached to the core; uses and compositions thereof.

Description

[Technical field]

[0001] Provided herein are antimicrobial particles comprising an organic or inorganic core, at least one antimicrobially active unit and at least one polymerizable unit, both covalently attached to the core; uses and compositions thereof. Also provided herein are matrices for various uses that incorporate the antimicrobial particles. [Background technology]

[0002] The overwhelming diversity of bacteria on the skin, gastrointestinal tract and oral cavity of an individual is well documented, demonstrating complex ecosystems, anatomically and dynamically, in which polymicrobial biofilms are the norm.

[0003] Biofilms formed on the outer and inner tissues of living organisms are the main cause of infectious diseases. For example, in the oral cavity, biofilms formed on the hard or soft tissues of teeth are the main cause of caries and periodontal disease (Sbordone L., Bortolaia C., Clin Oral Investig 2003;7:181-8). Bacterial biofilms form on both natural and artificial surfaces.

[0004] In recent years, special attention has been paid to artificial surfaces in contact with living organisms, since these surfaces lack epithelial shedding, the main natural mechanism for preventing biofilms, and thus biofilm accumulation is becoming a major cause of medical problems that can lead to life-threatening complications. Two main factors, surface roughness and surface free energy, a property of the material used, affect the susceptibility of a surface to accumulate bacteria. Surface roughness has a greater effect on bacterial attachment than surface free energy. In this context, artificial restorative materials generally have a higher surface roughness than natural surfaces and are therefore more prone to bacterial accumulation. The development of new materials that reduce biofilm formation is therefore an important topic.

[0005] The ultimate goal of developing materials with anti-biofilm properties is to promote health and reduce the occurrence of disease. None of the existing medical devices can guarantee immediate and comprehensive elimination of biofilms or prevention of secondary infections.

[0006] For example, to sustain oral defense, dental materials are required that have the following anti-biofilm properties: (1) inhibition of initial attachment of microorganisms, (2) prevention of biofilm growth, (3) effects on microbial metabolism in the biofilm, (4) killing of biofilm bacteria, and (5) detachment of the biofilm (Busscher HJ, Rinastiti M, Siswomihardjo W, van der Mei HC., J Dent Res, 2010; 89: 657-65; Marsh PD. J Dent, 2010; 38).

[0007] Quaternary ammonium compounds (QACs) are widely used in water, surface and equipment disinfection, as well as in textile, leather and food industries, due to their relatively low toxicity, broad antibacterial spectrum, non-volatility and chemical stability. Antibacterial particles based on quaternary ammonium groups have been developed as disclosed in U.S. Patent No. 11,134,676 and U.S. Patent No. 11,178,867. However, resin-based composites containing such antibacterial particles can lead to leaching from the resin-based composite, thereby causing the breakdown of antibacterial activity and increasing the risk of higher toxicity. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] U.S. Pat. No. 11,134,676 [Patent Document 2] U.S. Pat. No. 11,178,867 [Non-patent literature]

[0009] [Non-Patent Document 1] Sbordone L., Bortolaia C., Clin Oral Investig 2003;7:181-8 [Non-Patent Document 2] Busscher HJ, Rinastiti M, Siswomihardjo W, van der Mei HC., J Dent Res, 2010;89:657-65 [Non-Patent Document 3] Marsh PD.J Dent,2010;38 Summary of the Invention [Problem to be solved by the invention]

[0010] The present invention provides antimicrobial particles and resin-based composites containing same that have reduced leaching properties yet maintain antimicrobial activity. [Means for solving the problem]

[0011] The following is a simplified summary to provide an initial understanding of the invention. The summary does not necessarily identify key elements, nor is it intended to limit the scope of the invention, and is merely intended to serve as a guide for the description that follows.

[0012] One aspect of the invention provides antimicrobial particles comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized with at least one antimicrobial group or at least one functional polymerizable group, the functional polymerizable group comprising an acrylate (e.g., a substituted or unsubstituted acrylate group), an epoxy (e.g., a substituted or unsubstituted epoxy group), an isocyanate and / or a vinyl group (e.g., a substituted or unsubstituted vinyl group), and wherein the molar ratio of silicon atoms functionalized with the at least one antimicrobial group to silicon atoms functionalized with the at least one functional polymerizable group is from 10:1 to 1:10, respectively.

[0013] One aspect of the invention provides antimicrobial particles comprising a polyhedral oligomeric silsesquioxane (POSS) core, the silicon atoms of the POSS being functionalized with at least one antimicrobial group and at least one functional polymerizable group; the at least one functional polymerizable group comprises a substituted and / or unsubstituted acrylate group, an epoxy group, a vinyl group, and / or an isocyanate group; The antibacterial unit has the structure (1): [ka] wherein: L1 is a first linker or bond; L2 is a second linker, L3 is a third linker or bond, R1 and R1' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R2 and R2' are each independently an alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R3 and R3' are each independently nothing, hydrogen, alkyl, a terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl, or any combination thereof, and when R3 or R3' is nothing, the nitrogen is uncharged; X1 and X2 are each independently a bond, alkylene, alkenylene, or alkynylene; Each n1 is independently an integer of 0 to 200, Each n2 is independently an integer of 0 to 200, n1+n2≧1; m is an integer from 1 to 200, and the repeating units are the same or different; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0014] In another embodiment, the antimicrobial group is -N(R1)(R2)(R3) + , -N(R1)(R2) + -, -N(R1')(R2')(R3') + or -N(R1')(R2') + - (all possibilities are covalently bonded to X1 or X2).

[0015] One aspect of the present invention provides a composition comprising a plurality of the disclosed antimicrobial particles and a polymeric material as a matrix.

[0016] These, additional and / or other aspects and / or advantages of the present invention will be set forth in the following detailed description, and / or may be inferred from the detailed description and / or learned by practice of the invention.

[0017] The subject matter which is regarded as the invention is particularly pointed out and distinctly claimed in the concluding portion of this specification, however the invention, both as to organization and method of operation, together with objects, features, and advantages thereof, may best be understood by reference to the following detailed description taken in conjunction with the accompanying drawings, in which: [Brief description of the drawings]

[0018] [Figure 1A] 1A-1C show schemes of antimicrobial particles of the invention comprising antimicrobially active unit(s) and polymerizable unit(s), according to some embodiments of the invention. FIG. 1A shows a particle (6) with the same number of antimicrobially active units and polymerizable units. FIG. 1B shows a particle with more antimicrobially active units than polymerizable units (7 versus 5, respectively). FIG. 1C shows a particle with more polymerizable units than antimicrobially active units (7 versus 5, respectively). It can be seen in FIGS. 1A-1C that the (antimicrobially active and polymerizable) units may be the same or different, as can be inferred from the term "...unit 1" or "...unit 2". [Figure 1B]1A-1C show schemes of antimicrobial particles of the invention comprising antimicrobially active unit(s) and polymerizable unit(s), according to some embodiments of the invention. FIG. 1A shows a particle (6) with the same number of antimicrobially active units and polymerizable units. FIG. 1B shows a particle with more antimicrobially active units than polymerizable units (7 versus 5, respectively). FIG. 1C shows a particle with more polymerizable units than antimicrobially active units (7 versus 5, respectively). It can be seen in FIGS. 1A-1C that the (antimicrobially active and polymerizable) units may be the same or different, as can be inferred from the term "...unit 1" or "...unit 2". [Figure 1C] 1A-1C show schemes of antimicrobial particles of the invention comprising antimicrobially active unit(s) and polymerizable unit(s), according to some embodiments of the invention. FIG. 1A shows a particle (6) with the same number of antimicrobially active units and polymerizable units. FIG. 1B shows a particle with more antimicrobially active units than polymerizable units (7 versus 5, respectively). FIG. 1C shows a particle with more polymerizable units than antimicrobially active units (7 versus 5, respectively). It can be seen in FIGS. 1A-1C that the (antimicrobially active and polymerizable) units may be the same or different, as can be inferred from the term "...unit 1" or "...unit 2". [Figure 2A] 2A shows an antimicrobial active unit and an (antimicrobial) monomeric unit according to some embodiments of the present invention. FIG. 2A shows an antimicrobial active unit. FIG. 2B shows an (antimicrobial) monomeric unit. [ka] The concept of "bonding" is defined as the binding to the inorganic or organic core of the antimicrobial particles of the present invention. [Figure 2B] 2A shows an antimicrobial active unit and an (antimicrobial) monomeric unit according to some embodiments of the present invention. FIG. 2A shows an antimicrobial active unit. FIG. 2B shows an (antimicrobial) monomeric unit. [ka] The concept of "bonding" is defined as the binding to the inorganic or organic core of the antimicrobial particles of the present invention. [Figure 3A] 3A shows a polymerizable unit and a (polymerizable) monomer unit according to some embodiments of the present invention. FIG. 3A shows a polymerizable unit. FIG. 3B shows a (polymerizable) monomer unit. [ka] The concept of "bonding" is defined as the binding to the inorganic or organic core of the antimicrobial particles of the present invention. [Figure 3B] 3A shows a polymerizable unit and a (polymerizable) monomer unit according to some embodiments of the present invention. FIG. 3A shows a polymerizable unit. FIG. 3B shows a (polymerizable) monomer unit. [ka] The concept of "bonding" is defined as the binding to the inorganic or organic core of the antimicrobial particles of the present invention. [Figure 4] 1 shows a representative scheme for the preparation of standard particles according to some embodiments of the present invention, in which the antimicrobial active group is a tertiary amine or quaternary ammonium group containing at least one terpenoid moiety, and the antimicrobial unit has one monomer unit (monomer backbone). The circle represents an organic or inorganic core, R1-Y-R1 is C1-C4 alkyl, and Y is a leaving group such as a halogen or sulfonate. [Diagram 5] 1 shows a representative scheme for preparing standard particles according to some embodiments of the present invention, the particles have cinnamyl groups with a core (represented by a circle) via an amino-functional linker, and the antimicrobial unit has one monomer unit (monomer backbone). The conversion of the tertiary amine to a quaternary ammonium group is optional and involves the reaction of the tertiary amine with a group R1-Y, where R1 is a C1-C4 alkyl and Y is a leaving group such as a halogen or sulfonate. [Figure 6A]6A-6C show representative schemes of three routes for the preparation of quaternary ammonium salt (QAS)-functionalized standard particles according to some embodiments of the present invention, where the antimicrobial unit has one monomer unit (monomer backbone) and the circles represent organic or inorganic cores. FIG. 6A) Reductive amination to achieve tertiary amines, followed by alkylation reaction; FIG. 6B) Stepwise alkylation reaction; and FIG. 6C) Reacting a linker functionalized with a leaving group (e.g., Cl or another halogen) with a tertiary amine. R1 and R2 represent C1-C4 alkyl, e.g., methyl, ethyl, propyl or isopropyl. R1 and R2 may be different or the same group. Y represents any leaving group, e.g., Cl, Br or I, or a sulfonate (e.g., mesyl, tosyl). [Figure 6B] 6A-6C show representative schemes of three routes for the preparation of quaternary ammonium salt (QAS)-functionalized standard particles according to some embodiments of the present invention, where the antimicrobial unit has one monomer unit (monomer backbone) and the circles represent organic or inorganic cores. FIG. 6A) Reductive amination to achieve tertiary amines, followed by alkylation reaction; FIG. 6B) Stepwise alkylation reaction; and FIG. 6C) Reacting a linker functionalized with a leaving group (e.g., Cl or another halogen) with a tertiary amine. R1 and R2 represent C1-C4 alkyl, e.g., methyl, ethyl, propyl or isopropyl. R1 and R2 may be different or the same group. Y represents any leaving group, e.g., Cl, Br or I, or a sulfonate (e.g., mesyl, tosyl). [Figure 6C]6A-6C show representative schemes of three routes for the preparation of quaternary ammonium salt (QAS)-functionalized standard particles according to some embodiments of the present invention, where the antimicrobial unit has one monomer unit (monomer backbone) and the circles represent organic or inorganic cores. FIG. 6A) Reductive amination to achieve tertiary amines, followed by alkylation reaction; FIG. 6B) Stepwise alkylation reaction; and FIG. 6C) Reacting a linker functionalized with a leaving group (e.g., Cl or another halogen) with a tertiary amine. R1 and R2 represent C1-C4 alkyl, e.g., methyl, ethyl, propyl or isopropyl. R1 and R2 may be different or the same group. Y represents any leaving group, e.g., Cl, Br or I, or a sulfonate (e.g., mesyl, tosyl). [Figure 7A] 7A-7C show representative schemes of three routes for the preparation of functionalized particles of quaternary ammonium salts (QAS) with improved thermal stability according to some embodiments of the present invention, where the antimicrobial unit has one monomer unit (monomer backbone). The circles represent organic or inorganic cores. FIG. 7A) Alkylation with R1-Y / R2-Y to achieve a tertiary amine, followed by a benzylation reaction; FIG. 7B) Similar route to A), but performed in reverse order; and FIG. 7C) Reaction of a linker functionalized with a leaving group (e.g., Cl or other halogen) with a tertiary amine. R4 and R5 are independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C20 alkyl, 2,2,2-trisubstituted ethyl, -CH2C(=O)OR, -CH2C(=O)OC(=O)R, -CH2C(=S)OR, -CH2C(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -CH2C(=O)R, -CH2C(=S)R, -CH2CF3, -CH2NO2, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof, where R is alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof. Y represents any leaving group, such as Cl, Br, or I, or a sulfonate (e.g., mesyl, tosyl). [Figure 7B]7A-7C show representative schemes of three routes for the preparation of functionalized particles of quaternary ammonium salts (QAS) with improved thermal stability according to some embodiments of the present invention, where the antimicrobial unit has one monomer unit (monomer backbone). The circles represent organic or inorganic cores. FIG. 7A) Alkylation with R1-Y / R2-Y to achieve a tertiary amine, followed by a benzylation reaction; FIG. 7B) Similar route to A), but performed in reverse order; and FIG. 7C) Reaction of a linker functionalized with a leaving group (e.g., Cl or other halogen) with a tertiary amine. R4 and R5 are independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C20 alkyl, 2,2,2-trisubstituted ethyl, -CH2C(=O)OR, -CH2C(=O)OC(=O)R, -CH2C(=S)OR, -CH2C(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -CH2C(=O)R, -CH2C(=S)R, -CH2CF3, -CH2NO2, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof, where R is alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof. Y represents any leaving group, such as Cl, Br, or I, or a sulfonate (e.g., mesyl, tosyl). [Figure 7C]7A-7C show representative schemes of three routes for the preparation of functionalized particles of quaternary ammonium salts (QAS) with improved thermal stability according to some embodiments of the present invention, where the antimicrobial unit has one monomer unit (monomer backbone). The circles represent organic or inorganic cores. FIG. 7A) Alkylation with R1-Y / R2-Y to achieve a tertiary amine, followed by a benzylation reaction; FIG. 7B) Similar route to A), but performed in reverse order; and FIG. 7C) Reaction of a linker functionalized with a leaving group (e.g., Cl or other halogen) with a tertiary amine. R4 and R5 are independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C20 alkyl, 2,2,2-trisubstituted ethyl, -CH2C(=O)OR, -CH2C(=O)OC(=O)R, -CH2C(=S)OR, -CH2C(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -CH2C(=O)R, -CH2C(=S)R, -CH2CF3, -CH2NO2, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof, where R is alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof. Y represents any leaving group, such as Cl, Br, or I, or a sulfonate (e.g., mesyl, tosyl). [Figure 8] 1 shows schemes of solid support and solution methods for preparing standard particles with antimicrobial units having one monomer unit (monomer backbone) according to some embodiments of the present invention. The circles represent organic or inorganic cores. Q1, Q2 and Q3 are independently selected from the group consisting of ethoxy, methoxy, methyl, ethyl, hydrogen, sulfonate and halide, and at least one of Q1, Q2 and Q3 is a leaving group selected from ethoxy, methoxy, sulfonate (e.g., mesyl, tosyl) and halide. For clarity, the schemes represent the cases where Q1, Q2 and Q3 represent leaving groups, Q4 represents an antimicrobial group, W is selected from the group consisting of NH2, halide, sulfonate and hydroxyl, and n is an integer from 1 to 16. [Figure 9-1]FIG. 1 shows a representative scheme for preparing standard particles according to some embodiments of the present invention, the particles having di-cinnamyl groups with a core particle (represented as a circle) functionalized by both solid support and solution methods utilizing an (EtO)Si-CH-(CH)-CHNH linker, the antimicrobial unit having one monomer unit (monomer backbone), where n is an integer between 1 and 16. [Figure 9-2] FIG. 1 shows a representative scheme for preparing standard particles according to some embodiments of the present invention, the particles having di-cinnamyl groups with a core particle (represented as a circle) functionalized by both solid support and solution methods utilizing an (EtO)Si-CH-(CH)-CHNH linker, the antimicrobial unit having one monomer unit (monomer backbone), where n is an integer between 1 and 16. [Figure 10-1] 1 shows a representative scheme for preparing standard particles by solid support method according to some embodiments of the present invention, where the antimicrobial unit has an oligomeric or polymeric backbone (multiple monomeric units). The circle represents the core. The starting material is a core terminated with hydroxyl groups at the surface, Q101, Q102 and Q103, and independently, are alkoxy, alkyl or aryl, LG is Cl, Br, I, mesylate, tosylate or triflate, Hal is Cl, Br or I, q1, q2 and q3 are independently integers from 0 to 16, R1 and R2 are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl or any combination thereof, and R3 is nothing, hydrogen, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl or any combination thereof. [Figure 10-2]1 shows a representative scheme for preparing standard particles by solid support method according to some embodiments of the present invention, where the antimicrobial unit has an oligomeric or polymeric backbone (multiple monomeric units). The circle represents the core. The starting material is a core terminated with hydroxyl groups at the surface, Q101, Q102 and Q103, and independently, are alkoxy, alkyl or aryl, LG is Cl, Br, I, mesylate, tosylate or triflate, Hal is Cl, Br or I, q1, q2 and q3 are independently integers from 0 to 16, R1 and R2 are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl or any combination thereof, and R3 is nothing, hydrogen, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl or any combination thereof. [Figure 11-1]1 shows an exemplary scheme for preparing particles with enhanced thermal stability by solid support methods according to some embodiments of the present invention, where the antimicrobial units have an oligomeric or polymeric backbone (multiple monomeric units). The circle represents the core. The starting material is a surface hydroxyl terminated core, Q101, Q102 and Q103 are each independently alkoxy, alkyl or aryl, LG is Cl, Br, I, mesylate, tosylate or triflate, Hal is Cl, Br or I, q, q1, q2 and q3 are each independently an integer between 0 and 16, R4 and R5 are each independently methyl, CF 3. Perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C20 alkyl, 2,2,2-trisubstituted ethyl, -CH2C(=O)OR, -CH2C(=O)OC(=O)R, -CH2C(=S)OR, -CH2C(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CH2C(=O)R, -CH2C(=S) R, -CH2CF3, -CH2NO2, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R6 is methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C20 alkyl, 2,2,2-trisubstituted ethyl, -CH2C(=O)OR, -CH2C(=O)OC(=O)R, -CH2C(=S)OR, -CH2C(=O)SR, -C(=O)OR, -C (=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, a terpenoid moiety, cycloalkyl, aryl, phenyl, benzyl, heterocycle, conjugate alkyl, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof. [Figure 11-2]1 shows an exemplary scheme for preparing particles with enhanced thermal stability by solid support methods according to some embodiments of the present invention, where the antimicrobial units have an oligomeric or polymeric backbone (multiple monomeric units). The circle represents the core. The starting material is a surface hydroxyl terminated core, Q101, Q102 and Q103 are each independently alkoxy, alkyl or aryl, LG is Cl, Br, I, mesylate, tosylate or triflate, Hal is Cl, Br or I, q, q1, q2 and q3 are each independently an integer between 0 and 16, R4 and R5 are each independently methyl, CF 3. Perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C20 alkyl, 2,2,2-trisubstituted ethyl, -CH2C(=O)OR, -CH2C(=O)OC(=O)R, -CH2C(=S)OR, -CH2C(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CH2C(=O)R, -CH2C(=S) R, -CH2CF3, -CH2NO2, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R6 is methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C20 alkyl, 2,2,2-trisubstituted ethyl, -CH2C(=O)OR, -CH2C(=O)OC(=O)R, -CH2C(=S)OR, -CH2C(=O)SR, -C(=O)OR, -C (=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, a terpenoid moiety, cycloalkyl, aryl, phenyl, benzyl, heterocycle, conjugate alkyl, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof. [Figure 12A] Figure 12 shows the self-polymerization of trialkoxysilane linkers on standard particles according to some embodiments of the present invention: Figure 12A: Self-polymerization of trialkoxysilane linkers by solid support method; Figure 12B: Self-polymerization of trialkoxysilane linkers in solution; and Figure 12C: Polymerization of silane groups compared to simple silanization. [Figure 12B] Figure 12 shows the self-polymerization of trialkoxysilane linkers on standard particles according to some embodiments of the present invention: Figure 12A: Self-polymerization of trialkoxysilane linkers by solid support method; Figure 12B: Self-polymerization of trialkoxysilane linkers in solution; and Figure 12C: Polymerization of silane groups compared to simple silanization. [Figure 12C] Figure 12 shows the self-polymerization of trialkoxysilane linkers on standard particles according to some embodiments of the present invention: Figure 12A: Self-polymerization of trialkoxysilane linkers by solid support method; Figure 12B: Self-polymerization of trialkoxysilane linkers in solution; and Figure 12C: Polymerization of silane groups compared to simple silanization. [Figure 13A] Figure 13 shows the self-polymerization of trialkoxysilane linkers in particles with improved thermal stability according to some embodiments of the present invention: Figure 13A: Self-polymerization of trialkoxysilane linkers by solid support method; Figure 13B: Self-polymerization of trialkoxysilane linkers in solution; and Figure 13C: Polymerization of silane groups compared to simple silanization. [Figure 13B] Figure 13 shows the self-polymerization of trialkoxysilane linkers in particles with improved thermal stability according to some embodiments of the present invention: Figure 13A: Self-polymerization of trialkoxysilane linkers by solid support method; Figure 13B: Self-polymerization of trialkoxysilane linkers in solution; and Figure 13C: Polymerization of silane groups compared to simple silanization. [Figure 13C] Figure 13 shows the self-polymerization of trialkoxysilane linkers in particles with improved thermal stability according to some embodiments of the present invention: Figure 13A: Self-polymerization of trialkoxysilane linkers by solid support method; Figure 13B: Self-polymerization of trialkoxysilane linkers in solution; and Figure 13C: Polymerization of silane groups compared to simple silanization. [Figure 14-1]1 shows a representative scheme for preparing standard particles by solution method according to some embodiments of the present invention, where the antimicrobial unit has multiple monomer units (e.g., has an oligomeric or polymeric backbone). The circle represents the core. The starting material is a core terminated with a hydroxyl group at the surface, Q101, Q102 and Q103, and independently, are alkoxy, alkyl or aryl, LG is Cl, Br, I, mesylate, tosylate or triflate, Hal is Cl, Br or I, q1, q2 and q3 are independently integers from 0 to 16, R1 and R2 are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl or any combination thereof, and R3 is nothing, hydrogen, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl or any combination thereof. [Figure 14-2] 1 shows a representative scheme for preparing standard particles by solution method according to some embodiments of the present invention, where the antimicrobial unit has multiple monomer units (e.g., has an oligomeric or polymeric backbone). The circle represents the core. The starting material is a core terminated with a hydroxyl group at the surface, Q101, Q102 and Q103, and independently, are alkoxy, alkyl or aryl, LG is Cl, Br, I, mesylate, tosylate or triflate, Hal is Cl, Br or I, q1, q2 and q3 are independently integers from 0 to 16, R1 and R2 are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl or any combination thereof, and R3 is nothing, hydrogen, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl or any combination thereof. [Figure 15-1]FIG. 1 shows a representative scheme for preparing particles with enhanced thermal stability by solution processing, where the antimicrobial unit has multiple monomer units (e.g., has an oligomeric or polymeric backbone). The circle represents the core. The starting material is a surface-hydroxyl terminated core, Q101, Q102 and Q103, and each independently are alkoxy, alkyl or aryl, LG is Cl, Br, I, mesylate, tosylate or triflate, Hal is Cl, Br or I, q, q1, q2 and q3 are independently integers from 0 to 16, R4 and R5 are each independently methyl, CF3 , perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C20 alkyl, 2,2,2-trisubstituted ethyl, -CH2C(=O)OR, -CH2C(=O)OC(=O)R, -CH2C(=S)OR, -CH2C(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CH2C(=O)R, -CH2C(=S)R , -CH2CF3, -CH2NO2, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof, and R6 is methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C20 alkyl, 2,2,2-trisubstituted ethyl, -CH2C(=O)OR, -CH2C(=O)OC(=O)R, -CH2C(=S)OR, -CH2C(=O)SR, -C(=O)OR, -C (=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, a terpenoid moiety, cycloalkyl, aryl, phenyl, benzyl, heterocycle, conjugate alkyl, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof. [Figure 15-2]FIG. 1 shows a representative scheme for preparing particles with enhanced thermal stability by solution processing, where the antimicrobial unit has multiple monomer units (e.g., has an oligomeric or polymeric backbone). The circle represents the core. The starting material is a surface-hydroxyl terminated core, Q101, Q102 and Q103, and each independently are alkoxy, alkyl or aryl, LG is Cl, Br, I, mesylate, tosylate or triflate, Hal is Cl, Br or I, q, q1, q2 and q3 are independently integers from 0 to 16, R4 and R5 are each independently methyl, CF3 , perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C20 alkyl, 2,2,2-trisubstituted ethyl, -CH2C(=O)OR, -CH2C(=O)OC(=O)R, -CH2C(=S)OR, -CH2C(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CH2C(=O)R, -CH2C(=S)R , -CH2CF3, -CH2NO2, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof, and R6 is methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C20 alkyl, 2,2,2-trisubstituted ethyl, -CH2C(=O)OR, -CH2C(=O)OC(=O)R, -CH2C(=S)OR, -CH2C(=O)SR, -C(=O)OR, -C (=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, a terpenoid moiety, cycloalkyl, aryl, phenyl, benzyl, heterocycle, conjugate alkyl, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof. [Figure 16-1] FIG. 1 shows a representative scheme for preparing silica-based antimicrobial standard particles containing dimethylethylammonium as an antimicrobial active group by a solid support method, according to some embodiments of the present invention, where the antimicrobial unit has multiple monomer units (e.g., has an oligomeric or polymeric backbone). [Figure 16-2]FIG. 1 shows a representative scheme for preparing silica-based antimicrobial standard particles containing dimethylethylammonium as an antimicrobial active group by a solid support method, according to some embodiments of the present invention, where the antimicrobial unit has multiple monomer units (e.g., has an oligomeric or polymeric backbone). [Figure 17-1] FIG. 1 shows a representative scheme for preparing silica-based antimicrobial standard particles containing dimethylethylammonium as an antimicrobial active group by a solution process, according to some embodiments of the present invention, where the antimicrobial unit has multiple monomer units (e.g., has an oligomeric or polymeric backbone). [Figure 17-2] FIG. 1 shows a representative scheme for preparing silica-based antimicrobial standard particles containing dimethylethylammonium as an antimicrobial active group by a solution process, according to some embodiments of the present invention, where the antimicrobial unit has multiple monomer units (e.g., has an oligomeric or polymeric backbone). [Figure 18-1] FIG. 1 shows an exemplary scheme for preparing silica-based antimicrobial particles with improved thermal stability comprising dimethylbenzylammonium as the antimicrobially active group by a solid support method, according to some embodiments of the present invention, where the antimicrobial unit has multiple monomeric units (e.g., has an oligomeric or polymeric backbone). [Figure 18-2] FIG. 1 shows an exemplary scheme for preparing silica-based antimicrobial particles with improved thermal stability comprising dimethylbenzylammonium as the antimicrobially active group by a solid support method, according to some embodiments of the present invention, where the antimicrobial unit has multiple monomeric units (e.g., has an oligomeric or polymeric backbone). [Figure 19-1] FIG. 1 shows an exemplary scheme for the solution process preparation of silica-based antimicrobial particles with improved thermal stability comprising dimethylbenzylammonium as the antimicrobially active group, according to some embodiments of the present invention, wherein the antimicrobial unit has multiple monomeric units (e.g., has an oligomeric or polymeric backbone). [Figure 19-2]FIG. 1 shows an exemplary scheme for the solution process preparation of silica-based antimicrobial particles with improved thermal stability comprising dimethylbenzylammonium as the antimicrobially active group, according to some embodiments of the present invention, wherein the antimicrobial unit has multiple monomeric units (e.g., has an oligomeric or polymeric backbone). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0019] It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some elements may be exaggerated relative to other elements for clarity. Further, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or similar elements.

[0020] In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of the present invention. However, it will be understood by those skilled in the art that the present invention may be practiced without these specific details. In other instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the present invention.

[0021] antibacterial particles In some embodiments, provided herein is an antimicrobial particle comprising an organic or inorganic core, at least one antimicrobially active unit and at least one polymerizable unit, both covalently attached to the core. In one embodiment, the antimicrobial particle comprises a plurality of the same or different antimicrobially active units. In one embodiment, the antimicrobial particle comprises a plurality of the same or different polymerizable units. In a further embodiment, the antimicrobial particle comprises the same or different antimicrobially active units in a molar ratio of 10:1 to 1:10 to the same or different polymerizable units. In another embodiment, the ratio is 9:1 to 1:9. In another embodiment, the ratio is 8:1 to 1:8. In another embodiment, the ratio is 7:1 to 1:7. In another embodiment, the ratio is 6:1 to 1:6. In another embodiment, the ratio is 5:1 to 1:5. In another embodiment, the ratio is 4:1 to 1:4. In another embodiment, the ratio is 3:1 to 1:3. In another embodiment, the ratio is 2:1 to 1:2. In another embodiment, each antimicrobially active unit comprises one or more antimicrobial groups, said antimicrobially active units being chemically (covalently) bound to the core (surface) directly or indirectly (e.g., via a linker and / or other chemical moiety). In one embodiment, each polymerizable unit comprises one or more functional polymerizable groups, said polymerizable units being chemically (covalently) bound to the core (surface) directly or indirectly (e.g., via a linker and / or other chemical moiety). In one particular embodiment, the antimicrobial particle comprises an inorganic core, each silicon atom or metal atom in the surface of the inorganic core is functionalized with at least one antimicrobial group or at least one functional polymerizable group, and the molar ratio of silicon atoms or metal atoms in the surface of the inorganic core functionalized with at least one antimicrobial group to silicon atoms or metal atoms in the surface of the inorganic core functionalized with at least one functional polymerizable group is 10:1 to 1:10, respectively. In another embodiment, the ratio is 9:1 to 1:9. In another embodiment, the ratio is 8:1 to 1:8. In another embodiment, the ratio is from 7:1 to 1:7. In another embodiment, the ratio is from 6:1 to 1:6. In another embodiment, the ratio is from 5:1 to 1:5. In another embodiment, the ratio is from 4:1 to 1:4.In another embodiment, the ratio is 3:1 to 1:3. In another embodiment, the ratio is 2:1 to 1:2. In one embodiment, the functional polymerizable group comprises an acrylate, epoxy, vinyl, or isocyanate group. In one embodiment, the antimicrobial group is a quaternary ammonium, a tertiary amine, or a tertiary ammonium.

[0022] In some non-limiting embodiments, the antimicrobial particle is generally represented by Figures 1A-1C. In Figures 1A-1C, it can be seen that the (antimicrobially active and polymerizable) units can be the same or different, as can be inferred from the term "...unit 1" or "...unit 2." In Figure 1A, the number of antimicrobially active units and polymerizable units are the same (6). In Figure 1B, there are more antimicrobially active units than polymerizable units (7 versus 5, respectively). In Figure 1C, there are more polymerizable units than antimicrobially active units (7 versus 5, respectively).

[0023] In some embodiments, the antimicrobially active unit is represented diagrammatically by Figure 2A. In one embodiment, the antimicrobially active unit comprises a (polymeric / oligomeric) backbone covalently bonded to one or more monomers (or "monomeric units"), said backbone being covalently bonded via a bond or linker to an inorganic or organic core of the antimicrobial particle of the invention (" [ka] " concept. In a further embodiment, the monomer or monomer unit is generally represented by Figure 2B. In other embodiments, each monomer or monomer unit comprises an antimicrobial group.

[0024] In some embodiments, the polymerizable unit is represented diagrammatically by Figure 3A. In one embodiment, the polymerizable unit comprises a (polymeric / oligomeric) backbone covalently bonded to monomers (or "monomeric units"), said backbone being covalently bonded via a bond or linker to an inorganic or organic core of the antimicrobial particles of the invention (" [ka] " concept. In a further embodiment, the monomer or monomer unit is represented generally by Figure 3B. In other embodiments, each monomer or monomer unit comprises at least one functional polymerizable group.

[0025] In some embodiments, the number of antimicrobial activity units is determined based on the surface area of ​​the core of the particle. 2 ) is 0.01 to 30 units of antimicrobial activity per sq nm of core surface. In another embodiment, the number of units of antimicrobial activity is 0.01 to 20 units of antimicrobial activity per sq nm of core surface. In another embodiment, the number of units of antimicrobial activity is 0.01 to 10 units of antimicrobial activity per sq nm of core surface. In another embodiment, the number of units of antimicrobial activity is 0.01 to 15 units of antimicrobial activity per sq nm of core surface. In another embodiment, the number of units of antimicrobial activity is 0.01 to 5 units of antimicrobial activity per sq nm of core surface. Each possibility represents a separate embodiment of the present invention.

[0026] In some embodiments, the number of polymerizable units is less than 1 sq nm (nm 2 ) is 0.01 to 30 per sq nm of core surface. In another embodiment, the number of polymerizable units is 0.01 to 20 per sq nm of core surface. In another embodiment, the number of polymerizable units is 0.01 to 10 per sq nm of core surface. In another embodiment, the number of polymerizable units is 0.01 to 15 per sq nm of core surface. In another embodiment, the number of polymerizable units is 0.01 to 5 per sq nm of core surface. Each possibility represents a separate embodiment of the present invention.

[0027] Antibacterial activity unit A) Branched and unbranched units In some embodiments, the antimicrobially active unit has the structure (1): [ka] wherein: L1 is a first linker or bond; L2 is a second linker, L3 is a third linker or bond, R1 and R1' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R2 and R2' are each independently an alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R3 and R3' are each independently nothing, hydrogen, alkyl, a terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl, or any combination thereof, and when R3 or R3' is nothing, the nitrogen is uncharged; X1 and X2 are each independently a bond, alkylene, alkenylene, or alkynylene; Each n1 is independently an integer of 0 to 200, Each n2 is independently an integer of 0 to 200, n1+n2≧1; m is an integer from 1 to 200, and the repeating units are the same or different; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0028] In another embodiment, the antimicrobial group is -N(R1)(R2)(R3) + , -N(R1)(R2) + -, -N(R1')(R2')(R3') + or -N(R1')(R2') + - (all possibilities are covalently bonded to X1 or X2).

[0029] In another embodiment, the number of antimicrobial groups per each antimicrobially active unit is at least 2, e.g., n1+n2≧2 and m≧1 (“branched units”). In another embodiment, the number of antimicrobial groups per each antimicrobially active unit is 1, e.g., n1+n2=1 and m=1 (“non-branched units”).

[0030] In some embodiments, the antimicrobially active unit has the structure (2): [ka] wherein: L1 is a first linker or bond; L2 is a second linker, L3 is a third linker or bond, R1 and R1' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R2 and R2' are each independently an alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; X1 and X2 are each independently a bond, alkylene, alkenylene, or alkynylene; Each n1 is independently an integer of 0 to 200, Each n2 is independently an integer of 0 to 200, n1+n2≧1, m is an integer from 1 to 200, and the repeating units are the same or different; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0031] In another embodiment, the antimicrobial group is -HN(R1)(R2) + , -HN(R1) + -, -HN(R1')(R2') + or -HN(R1')+ - (all possibilities are covalently bonded to X1 or X2).

[0032] In another embodiment, the number of antimicrobial groups per each antimicrobially active unit is at least 2, e.g., n1+n2≧2 and m≧1 (“branched units”). In another embodiment, the number of antimicrobial groups per each antimicrobially active unit is 1, e.g., n1+n2=1 and m=1 (“non-branched units”).

[0033] In some embodiments, the antimicrobially active unit has the structure (3): [ka] wherein: L1 is a first linker or bond; L2 is a second linker, L3 is a third linker or bond, R1 and R1' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R2 and R2' are each independently an alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; X1 and X2 are each independently a bond, alkylene, alkenylene, or alkynylene; Each n1 is independently an integer of 0 to 200, Each n2 is independently an integer of 0 to 200, n1+n2≧1, m is an integer from 1 to 200, and the repeating units are the same or different; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0034] In another embodiment, the antibacterial group is -N(R1)(R2), -N(R1)-, -N(R1')(R2') or -N(R1')- (all possibilities covalently attached to X1 or X2).

[0035] In another embodiment, the number of antimicrobial groups per each antimicrobially active unit is at least 2, e.g., n1+n2≧2 and m≧1 (“branched units”). In another embodiment, the number of antimicrobial groups per each antimicrobially active unit is 1, e.g., n1+n2=1 and m=1 (“non-branched units”).

[0036] In another embodiment, the antimicrobially active units of structures (1)-(3) comprise one monomer unit per antimicrobially active unit. In another embodiment, the antimicrobially active units of structures (1)-(3) comprise multiple antimicrobial groups per antimicrobially active unit.

[0037] B) Unbranched units In some embodiments, the antimicrobially active unit has the structure (4): [ka] wherein: L1 is a first linker or bond; L3 is a third linker or bond, R1 is an alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R2 is an alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R3 is nothing, hydrogen, an alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, an alkenyl, an alkynyl, or any combination thereof; When R3 or R3' is absent, the nitrogen is uncharged; X is a bond, alkyl, alkenyl, or alkynyl; X' is nothing or hydrogen; When L1 and X are bonds, the nitrogen is part of an organic or inorganic core; At least one of R1, R2, and R3 is hydrophobic; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0038] In another embodiment, the antimicrobial group is {N(R1)(R2)(R3)} + (covalently bonded to X).

[0039] In some embodiments, the antimicrobially active unit has the structure (5): [ka] wherein: L1 is a first linker or bond; L3 is a third linker or bond, R1 is an alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R2 is an alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; X is a bond, alkyl, alkenyl, or alkynyl; X' is nothing or hydrogen; When L1 and X are bonds, the nitrogen is an integral part of the organic or inorganic core; At least one of R1 and R2 is hydrophobic; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0040] In another embodiment, the antimicrobial group is {HN(R1)(R2)} +(covalently bonded to X).

[0041] In some embodiments, the antimicrobially active unit has the structure (6): [ka] wherein: L1 is a first linker or bond; L3 is a third linker or bond, R1 is an alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R2 is an alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; X is a bond, alkyl, alkenyl, or alkynyl; X' is nothing or hydrogen; When L1 and X are bonds, the nitrogen is an integral part of the organic or inorganic core; At least one of R1 and R2 is hydrophobic; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0042] In another embodiment, the antimicrobial group is {N(R1)(R2))} (covalently attached to X).

[0043] Specific examples of the antibacterial active unit of the present invention are [ka] In the formula, n = 1 to 200, and [ka] The notion "refers to a covalent bond to an organic or inorganic core. In another embodiment, n=1-3. In another embodiment, n=3-20. In another embodiment, n=20-50. In another embodiment, n=50-100. In another embodiment, n=100-200. In another embodiment, the core is silica or a polyhedral oligomeric silsesquioxane (POSS).

[0044] In some embodiments, the terms "antimicrobial group" and "monomeric antimicrobial group" refer to the same thing and include protonated tertiary amines, tertiary amines or quaternary ammoniums and have the formula: [ka] wherein: R1 is an alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R2 is an alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R3 is nothing, hydrogen, alkyl, a terpenoid moiety, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof, and when R3 or R3' is nothing, the nitrogen is uncharged.

[0045] In another embodiment, at least one of R1, R2, or R3 is hydrophobic.

[0046] In another embodiment, the number of antimicrobial groups per each unit of antimicrobial activity is at least 2, e.g., n1+n2≧1 and m≧1. In another embodiment, the number of antimicrobial groups per each unit of antimicrobial activity is 1, e.g., n1+n2=2 and m=1.

[0047] In another embodiment, the antimicrobially active units of structures (4)-(6) comprise one monomer unit. In another embodiment, the antimicrobially active units of structures (1)-(3) comprise one or more antimicrobial groups.

[0048] In another embodiment, the antimicrobially active units of structures (1)-(6) are covalently attached to an inorganic core. In another embodiment, the antimicrobially active units of structures (1)-(6) are covalently attached to an organic core. In another embodiment, the organic core is a polymeric organic core. In another embodiment, the core is inert. In one embodiment, the antimicrobially active units of the present invention represented by structures (1)-(3) are - + N(R1)(R2)(R3), - + N(R1)(R2)-,- + NH(R1)(R2), - + NH(R1)-, -N(R1)(R2), -N(R1)-, - + N(R1')(R2')(R3'), - + N(R1')(R2')-, - + NH(R1')(R2'), - +The antimicrobial group includes NH(R1')-, -N(R1')(R2') or -N(R1')-. In one embodiment, R1 and / or R1', R2 and / or R2', and R3 and / or R3' are the same or different and are independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl, or any combination thereof. In another embodiment, R1, R2 and R3 are independently alkyl. In another embodiment, R1 and / or R1', R2 and / or R2', and R3 and / or R3' are independently terpenoid. In another embodiment, R1 and / or R1', R2 and / or R2', and R3 and / or R3' are independently cycloalkyl. In another embodiment, R1 and / or R1', R2 and / or R2', and R3 and / or R3' are independently aryl. In another embodiment, R1 and / or R1', R2 and / or R2', and R3 and / or R3' are independently heterocycles. In another embodiment, R1 and / or R1', R2 and / or R2', and R3 and / or R3' are independently alkenyl. In another embodiment, R1 and / or R1', R2 and / or R2', and R3 and / or R3' are independently alkynyl. In another embodiment, R3 is nothing. In another embodiment, R3 and / or R3' is hydrogen. In another embodiment, at least one of R1 and / or R1', R2 and / or R2', and R3 and / or R3' is hydrophobic alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof. Each represents a separate embodiment of the present invention.

[0049] In another embodiment, R1 and R1' are the same. In another embodiment, R2 and R2' are the same. In another embodiment, R3 and R3' are the same. In another embodiment, R1 and R1' are different. In another embodiment, R2 and R2' are different. In another embodiment, R3 and R3' are different.

[0050] In one embodiment, at least one of R1, R2 and R3, and / or at least one of R1', R2' and R3' in structure (1) is hydrophobic. In one embodiment, at least one of R1 and R2, and / or at least one of R1' and R2' in structures (2) and (3) is hydrophobic.

[0051] The term "hydrophobic" refers to an alkyl, alkenyl, or alkynyl having at least 4 carbons, or the term hydrophobic refers to a terpenoid, cycloalkyl, aryl, or heterocycle having at least 6 carbons. Each possibility represents a separate embodiment of the present invention.

[0052] In one embodiment, at least one of R1, R2 and R3, and / or at least one of R1', R2' and R3' in structure (1) is a C4-C 24 Alkyl, C4-C 24 Alkenyl, C4-C 24 In one embodiment, at least one of R and R in structures (2) and (3) and / or at least one of R and R are C4-C 24 Alkyl, C4-C 24 Alkenyl, C4-C 24 alkynyl, or terpenoid. Each possibility represents a separate embodiment of the present invention.

[0053] In one embodiment, at least one of R1, R2, and R3, and / or at least one of R1', R2', and R3' in structure (1) is a C4-C8 alkyl, C4-C8 alkenyl, C4-C8 alkynyl, or terpenoid. In one embodiment, at least one of R1 and R2, and / or at least one of R1' and R2' in structures (2) and (3) is a C4-C8 alkyl, C4-C8 alkenyl, C4-C8 alkynyl, or terpenoid. Each possibility represents a separate embodiment of the present invention.

[0054] In one embodiment, R1 and / or R1' in structures (1)-(6) are terpenoids. In another embodiment, R1 and / or R1' are terpenoids and R2 and / or R2' are C1-C4 alkyl. In another embodiment, the core is an organic polymer core, R3 and / or R3' are nothing, and R1 and / or R1' are terpenoids. In another embodiment, the core is an organic polymer core, R3 and / or R3' are hydrogen, and R1 and / or R1' are terpenoids. In another embodiment, the core is an inorganic core, R3 and / or R3' are nothing, and R1 and / or R1' are terpenoids. In another embodiment, the core is an inorganic core, R3 and / or R3' are hydrogen, and R1 and / or R1' are terpenoids. In another embodiment, the core is an inorganic core, R3 and / or R3' are hydrogen, and R1 and / or R1' are terpenoids. In another embodiment, the core is an inorganic core, R3 and / or R3' are C1-C4 alkyl. 24 Alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, conjugated C1-C 24 Alkyl, C1-C 24 Alkenyl, C1-C 24 alkynyl, or any combination thereof, wherein R1 and / or R1' are terpenoids.

[0055] In one embodiment, the particles of the invention comprise an antimicrobially active unit and an inert core, wherein the antimicrobially active unit and the core are indirectly linked.

[0056] In some embodiments, L1, L2 or L3 are each independently the same linker or different linkers. In some embodiments, L1, L2 or L3 are bonded to each other in any possible way. In some embodiments, L3 is nothing (or is a bond) and L1 or L2 is covalently bonded to the core. In another embodiment, L3 is covalently bonded to the core and L1 or L2 is bonded to L3. In another embodiment, L1 is bonded to X, X' and L3 or to the core. In another embodiment, "linker" includes any possible chemical moiety that can link at least two other chemical moieties adjacent to such linker. In another embodiment, the monomeric unit of the antimicrobially active unit includes a first linker and / or a second linker (L1 or L2) and an antimicrobial group. In another embodiment, L1 and / or L2 are the backbone of the antimicrobially active unit. In another embodiment, the monomeric unit of the antimicrobially active unit includes a first linker and / or a second linker (L1 or L2) and an antimicrobial group. In another embodiment, L1 and / or L2 are the backbone of the antimicrobially active unit (which are, for example, alkylene, polypeptide or oligosiloxane (-Si(OH)2-O- or -Si(CH3)2-O-) moieties).

[0057] In some embodiments, the linker comprises a functional group. In another embodiment, the linker comprises two (the same or different) functional groups. In another embodiment, the functional group comprises a phosphate, a phosphonate, a siloxane, a silane, an ether acetal, an amide, an amine, an anhydride, an ester, a ketone, or one or more aromatic rings functionalized with any of the foregoing moieties. Each possibility represents a separate embodiment of the present invention.

[0058] In another embodiment, L1 or L2 is a C1-C18 alkylene, alkenylene, alkynylene or aryl substituted with at least one carboxyl moiety, the carboxyl terminus being attached to the core. The linker is substituted with at least one carboxyl moiety and is linked to an antimicrobial group [- + N(R1)(R2)(R3), - +N(R1)(R2)-,- + NH(R1)(R2), - + NH(R1)-, -N(R1)(R2), -N(R1)-, - + N(R1')(R2')(R3'), - + N(R1')(R2')-, - + NH(R1')(R2'), - + The linker may be derived from a C1-C18 alkylene having an amino terminus modified to NH(R1')-, -N(R1')(R2') or -N(R1')- (as defined in structures (1)-(6)). The linker may be derived from an amino acid (polypeptide) of natural or synthetic origin having a chain length of 2 to 18 carbon atoms, or an acyl halide of said amino acid. Non-limiting examples of such amino acids are 18-aminooctadecanoic acid and 18-aminostearic acid. In another embodiment, L1 or L2 is a C1-C18 alkylene substituted with at least one amine or amide moiety.

[0059] In another embodiment, L1, L2, L3 or any combination thereof is a C1-C18 alkylene, alkenylene, alkynylene or aryl. This linker, each end of which is functionalized with a core and an antibacterial group, replaces the halogen moiety from the dihaloalkylene to a functional group that attaches to the core, and replaces the halogen moiety to [- + N(R1)(R2)(R3), - + N(R1)(R2)-,- + NH(R1)(R2), - + NH(R1)-, -N(R1)(R2), -N(R1)-, - + N(R1')(R2')(R3'), - + N(R1')(R2')-, - + NH(R1')(R2'), - + It can be derived by obtaining -NH(R1')-, -N(R1')(R2') or -N(R1')- (as defined in structures (1) to (6)).

[0060] In another embodiment, L1, L2, L3 or any combination thereof is an aromatic group derived from the non-limiting examples of 4,4-biphenol, dibenzoic acid, dibenzoic halide, dibenzoic sulfonate, terephthalic acid, tetrphthalic halide, and terephthalic acid sulfonate. The linker is functionalized with the core and antibacterial group through its functional group (e.g., hydroxyl, carboxy, or sulfonate), respectively. In another embodiment, the linker is attached to the core directly at one end or indirectly through a third linker (L3) and to the antibacterial group [- + N(R1)(R2)(R3), - + N(R1)(R2)-,- + NH(R1)(R2), - + NH(R1)-, -N(R1)(R2), -N(R1)-, - + N(R1')(R2')(R3'), - + N(R1')(R2')-, - + NH(R1')(R2'), - + -NH(R1')-, -N(R1')(R2') or -N(R1')- (defined in structures (1) to (6))).

[0061] In another embodiment, L1, L2, L3 or any combination thereof is a siloxane or silane group derived and / or selected from the non-limiting examples of trialkoxyalkylsilane, trialkoxyarylsilane, trihaloalkylsilane, trihaloarylsilane, 3-aminopropyltriethoxysilane (APTES), (3-glycidyloxypropyl)trimethoxysilane, and N-2-aminoethyl-3-aminopropyltrimethoxysilane. The linker is functionalized with the core and antimicrobial group, respectively, through its functional group (e.g., hydroxyl, siloxane, carboxy, amide, or sulfonate). In another embodiment, the linker is attached to the core directly at one end or indirectly through a third linker (L3) and to the antimicrobial group [- + N(R1)(R2)(R3), - + N(R1)(R2)-,- +NH(R1)(R2), - + NH(R1)-, -N(R1)(R2), -N(R1)-, - + N(R1')(R2')(R3'), - + N(R1')(R2')-, - + NH(R1')(R2'), - + -NH(R1')-, -N(R1')(R2') or -N(R1')- (defined in structures (1) to (6))).

[0062] In one embodiment, antimicrobial groups of the present invention can be selected from (a) tertiary amines (e.g., R3 and / or R3' are absent) or tertiary ammonium (e.g., R3 and / or R3' are hydrogen) comprising at least one terpenoid moiety, (b) quaternary ammonium groups comprising at least one terpenoid moiety, (c) quaternary ammonium groups comprising at least one alkyl group having from 4 to 24 carbon atoms, (d) tertiary amines (e.g., R3 and / or R3' are absent) or tertiary ammonium (e.g., R3 and / or R3' are hydrogen) comprising at least one alkyl group having from 4 to 24 carbon atoms. Each possibility represents a separate embodiment of the present invention.

[0063] The linker is functionalized with the core and the antimicrobial unit through its functional group (e.g., hydroxyl, siloxane, carboxy, amide or sulfonate), respectively. In another embodiment, the linker is attached to the core directly at one end or indirectly through a third linker (L3) and to the antimicrobial group [- + N(R1)(R2)(R3), - + N(R1)(R2)-,- + NH(R1)(R2), - + NH(R1)-, -N(R1)(R2), -N(R1)-, - + N(R1')(R2')(R3'), - + N(R1')(R2')-, - + NH(R1')(R2'), - +-NH(R1')-, -N(R1')(R2') or -N(R1')- (defined in structures (1) to (6))).

[0064] In another embodiment, the monomer units within the antimicrobially active units of the present invention (e.g., as illustrated in Figures 2A-2B and Formulas 1-6) have the structure of formula IA. [ka] wherein: R1 and R2 are independently linear or branched alkyl, terpenoid, cycloalkyl, aryl, heteroaryl, alkenyl, alkynyl, or any combination thereof; R3 is nothing, a straight or branched alkyl, a terpenoid, a cycloalkyl, an aryl, a heteroaryl, an alkenyl, an alkynyl, or any combination thereof; If R3 is empty, the nitrogen is uncharged. q is an integer from 0 to 16, The monomer units are chemically bound to the surface of the inorganic core either directly or via a third linker (L3).

[0065] In another embodiment, the monomer units within the antimicrobially active units of the present invention (e.g., as illustrated in Figures 2A-2B and Formulas 1-6) have the structure of formula IB [ka] wherein: R1 and R2 are independently linear or branched alkyl, terpenoid, cycloalkyl, aryl, heteroaryl alkenyl, alkynyl, or any combination thereof; R3 is nothing, a straight or branched alkyl, a terpenoid, a cycloalkyl, an aryl, a heteroaryl, an alkenyl, an alkynyl, or any combination thereof; If R3 is empty, the nitrogen is uncharged. q and q 1are independently an integer from 0 to 16, The monomer units are chemically bound to the surface of the inorganic core either directly or via a third linker (L3).

[0066] In another embodiment, a linker molecule that may be used in the process of preparing the antimicrobial particles of the present invention has the structure of formula IC [ka] wherein: Q 201 , Q 202 and Q 203 is independently selected from the group consisting of alkoxy, methyl, ethyl, hydrogen, sulfonate and halide; Q 201 , Q 202 and Q 203 is selected from ethoxy, methoxy, sulfonate (e.g., mesyl, tosyl) and halide; q is an integer from 0 to 16, The linker molecule can be chemically bonded to the surface of the inorganic core via a silicon atom; The antimicrobial groups are introduced by functionalizing a primary amine to provide an antimicrobially active tertiary amine or quaternary ammonium group containing at least one terpenoid group, as described above.

[0067] In another embodiment, a linker molecule that may be used in the process of preparing the antimicrobial particles of the present invention has the structure of formula ID [ka] wherein: Q 201 , Q 202 and Q 203 is independently selected from the group consisting of alkoxy, methyl, ethyl, hydrogen, sulfonate and halide; Q 201 , Q 202 and Q 203is selected from ethoxy, methoxy, sulfonate (e.g., mesyl, tosyl) and halide; W is selected from the group consisting of NH2, halide, sulfonate and hydroxyl; q is an integer from 0 to 16, the linker is capable of chemically bonding to the surface of the inorganic core via a silicon atom; The antibacterial group is introduced by substituting or converting group W into an antibacterial group.

[0068] Antibacterial group containing one long alkyl group.

[0069] According to another embodiment, the antimicrobial group of the present invention [- + N(R1)(R2)(R3), - + N(R1)(R2)-,- + NH(R1)(R2), - + NH(R1)-, -N(R1)(R2), -N(R1)-, - + N(R1')(R2')(R3'), - + N(R1')(R2')-, - + NH(R1')(R2'), - + NH(R1')-, -N(R1')(R2') or -N(R1')- (as defined in structures (1)-(6)) is a quaternary ammonium group, a tertiary amine or a tertiary ammonium group, where the nitrogen atom of each amine / ammonium group has at least one bond X1 or X2, at least one bond to an alkyl group (R1 and / or R1') having 4 to 24 carbon atoms. In another embodiment, the nitrogen atom of each amine / ammonium group has one bond to the core and one bond to an alkyl group (R1 and / or R1') having 4 to 24 carbon atoms.

[0070] In some embodiments, the nitrogen atom of each quaternary ammonium or tertiary ammonium group has (i) at least one bond to X1 or X2; and (ii) at least one bond to an alkyl group having 4 to 24 carbon atoms.

[0071] In some embodiments, the antimicrobial groups of formulas (1)-(6) are selected from: (a) a tertiary amine (R3 and / or R3' are absent) or a tertiary ammonium (R3 and / or R3' are H), where the nitrogen atom of each tertiary amine / ammonium has at least one bond to X1 or X2 and one bond to an alkyl group having 4 to 24 carbon atoms; (b) a tertiary amine (R3 and / or R3' are absent) or a tertiary ammonium (R3 and / or R3' are H), where the nitrogen atom of each tertiary amine / ammonium has at least one bond to X1 or X2 and one bond to an alkyl group having 4 to 24 carbon atoms; (c) tertiary amines or ammoniums, or salts of said tertiary amines, wherein the nitrogen atom of each tertiary amine / ammonium has one bond to X1 or X2 and two bonds to alkyl groups having 4 to 24 carbon atoms, which may be the same or different from each other; (d) quaternary ammonium groups, wherein the nitrogen atom of each quaternary ammonium group has at least one bond to X1 or X2 and one or two bonds to alkyl groups having 4 to 24 carbon atoms, which may be the same or different from each other. Each possibility represents a separate embodiment of the present invention.

[0072] The term "quaternary ammonium group" refers to a group of atoms consisting of a nitrogen atom having four substituents (other than hydrogen) attached thereto. In another embodiment, "quaternary ammonium group" refers to a group of atoms consisting of a nitrogen atom having four groups, each group attached to the nitrogen through a carbon atom. The term "long alkyl group" or chain refers to such an alkyl group or chain substituted on the nitrogen atom of a quaternary ammonium group and having from 4 to 24 carbon atoms. In some embodiments, the alkyl group is an alkyl group having from 4 to 18 carbon atoms. In some embodiments, the alkyl group is an alkyl group having from 4 to 8 carbon atoms. In some embodiments, the alkyl group is an alkyl group having from 4 to 10 carbon atoms. In other embodiments, the alkyl group is an alkyl group having 6, 7, or 8 carbon atoms, with each possibility representing a separate embodiment of the present invention.

[0073] C) Heat-stable antibacterial unit In one embodiment, the antimicrobially active unit has the structure (I): [ka] wherein: The core is an organic polymer or an inorganic material; L4 is a first linker or bond, L5 is a second linker, L6 is a third linker or bond, The Z1 is [ka] and The Z2 is [ka] and R4 and R4' are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R5 and R5' are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R and R are each independently absent, methyl, CF, perhaloalkyl, 2,2-disubstituted C-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, a terpenoid moiety, cycloalkyl, aryl, phenyl, benzyl, heterocycle, conjugated alkyl, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R7 and R7' are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R8 and R8' are each independently H, an alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; R9 and R9' are each independently H, an alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; R 10 and R 10 each ' is independently H, an alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; R 11 and R 11 each ' is independently H, an alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; X3 and X4 each independently represent a bond, alkylene, arylene, alkenylene, alkynylene, or any combination thereof; X5 and X6 each independently represent a bond, -OC(=O)-, methylene, -OC(=O)-CH2-, or a 2,2-disubstituted C2-C 20 alkylene, arylene, phenylene, benzylene, cycloalkylene, heterocycle, conjugated alkylene, terpenoid moiety, 1-alkenylene, 1-alkynylene, 2-alkenylene, 2-alkynylene, or any combination thereof; R is alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof; Each n1 is independently an integer of 0 to 200, Each n2 is independently an integer of 0 to 200, n1+n2≧1, m is an integer from 1 to 200, and the repeating units are the same or different; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0074] In another embodiment, the antibacterial group is Z1 or Z2 (both possibilities are covalently attached to X3 or X4).

[0075] In another embodiment, only one moiety on the ammonium in each antimicrobially active unit may have a beta hydrogen available for Hoffmann elimination, provided that Z1 or Z2 contains an ammonium nitrogen (not a pyridinium). In another embodiment, two moieties on the ammonium in each antimicrobially active unit may have a beta hydrogen available for Hoffmann elimination, provided that Z1 or Z2 contains an ammonium nitrogen (not a pyridinium). In another embodiment, the beta hydrogen available for Hoffmann elimination is one found on a beta aliphatic carbon (relative to the ammonium nitrogen) and can be eliminated to release an olefin and a tertiary amine.

[0076] In another embodiment, the antimicrobially active unit has the structure (IE): [ka] wherein: The core is an organic polymer or an inorganic material; L4 is a first linker or bond, L6 is a third linker or bond, The Z1 is [ka] and R4 is methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R5 is methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R6 is methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, terpenoid moiety, cycloalkyl, aryl, phenyl, benzyl, heterocycle, conjugated alkyl, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R7 is methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R8 is H, alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; R9 is H, alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; R 10 is H, alkyl, a terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl, or any combination thereof; R 11 is H, alkyl, a terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl, or any combination thereof; X3 is a bond, alkylene, arylene, alkenylene, alkynylene, or any combination thereof; X5 is a bond, -OC(=O)-, methylene, -OC(=O)-CH2-, or 2,2-disubstituted C2-C 20 alkylene, arylene, phenylene, benzylene, cycloalkylene, heterocycle, conjugated alkylene, terpenoid moiety, 1-alkenylene, 1-alkynylene, 2-alkenylene, 2-alkynylene, or any combination thereof; R is alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0077] In another embodiment, the antimicrobial group is Z1, which is covalently attached to X3.

[0078] In another embodiment, only one moiety on the ammonium in each antimicrobially active unit may have a beta hydrogen available for Hoffmann elimination, provided that Z1 contains an ammonium nitrogen (not a pyridinium).In another embodiment, two moieties on the ammonium in each antimicrobially active unit may have a beta hydrogen available for Hoffmann elimination, provided that Z1 or Z2 contains an ammonium nitrogen (not a pyridinium).

[0079] In another embodiment, the antimicrobially active unit has the structure (II): [ka] wherein: The core is an organic polymer or an inorganic material; L4 is a first linker or bond, L5 is a second linker, L6 is a third linker or bond, R4 and R4' are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R5 and R5' are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R6 and R6' are each independently methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, a terpenoid moiety, cycloalkyl, aryl, phenyl, benzyl, heterocycle, conjugated alkyl, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or combinations thereof; R7 and R7' are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R8 and R8' are each independently H, an alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; R9 and R9' are each independently H, an alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; R 10 and R 10 each ' is independently H, an alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; R 11 and R 11 each ' is independently H, an alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; X3 and X4 each independently represent a bond, alkylene, arylene, alkenylene, alkynylene, or any combination thereof; R is alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof; Each n1 is independently an integer of 0 to 200, Each n2 is independently an integer of 0 to 200, n3 and n4 each independently represent 0 or 1; n1+n2≧1, m is an integer from 1 to 200, and the repeating units are the same or different; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0080] In another embodiment, the antimicrobial group is -N(R4)(R5)(R6) + or -N(R4')(R5')(R6') + (all possibilities are covalently bonded to {(CH2)n3} or {(CH2)n4}).

[0081] In another embodiment, only one moiety on the ammonium in each antimicrobially active unit may have a beta hydrogen available for Hoffmann elimination.

[0082] In another embodiment, the antimicrobially active unit has the structure (III): [ka] wherein: The core is an organic polymer or an inorganic material; L4 is a first linker or bond, L5 is a second linker, L6 is a third linker or bond, X3 and X4 are each independently a bond, alkylene, arylene, alkenylene, alkynylene, or any combination thereof; Each n1 is independently an integer of 0 to 200, Each n2 is independently an integer of 0 to 200, n1+n2≧1, m is an integer from 1 to 200, and the repeating units are the same or different; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0083] In another embodiment, the antimicrobial group is -N(CH3)3 + (covalently bonded to {CH2}).

[0084] In another embodiment, the antimicrobially active unit has the structure (IV): [ka] wherein: The core is an organic polymer or an inorganic material; L4 is a first linker or bond, L5 is a second linker, L6 is a third linker or bond, X3 and X4 are each independently a bond, alkylene, arylene, alkenylene, alkynylene, or any combination thereof; Each n1 is independently an integer of 0 to 200, Each n2 is independently an integer of 0 to 200, n1+n2≧1, m is an integer from 1 to 200, and the repeating units are the same or different; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0085] In another embodiment, the antimicrobial group is -N(CH3)3 + (covalently bonded to {C6H4}).

[0086] In another embodiment, the antimicrobially active unit has the structure (V): [ka] wherein: The core is an organic polymer or an inorganic material; L4 is a first linker or bond, L5 is a second linker, L6 is a third linker or bond, X3 and X4 are each independently a bond, alkylene, arylene, alkenylene, alkynylene, or a combination thereof; Each n1 is independently an integer of 0 to 200, Each n2 is independently an integer of 0 to 200, n1+n2≧1, m is an integer from 1 to 200, and the repeating units are the same or different; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0087] In another embodiment, the antimicrobial group is -N(CH3)3 + (covalently bonded to {C6H4}).

[0088] In another embodiment, the antimicrobially active unit has the structure (VI): [ka] wherein: The core is an organic polymer or an inorganic material; L4 is a first linker or bond, L5 is a second linker, L6 is a third linker or bond, X3 and X4 are each independently a bond, alkylene, arylene, alkenylene, alkynylene, or a combination thereof; Each n1 is independently an integer of 0 to 200, Each n2 is independently an integer of 0 to 200, n1+n2≧1, m is an integer from 1 to 200, and the repeating units are the same or different; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0089] In another embodiment, the antimicrobial group is -N(CH3)3 + (covalently bonded to {CH2}).

[0090] In another embodiment, the antimicrobially active unit has structure (VII): [ka] wherein: The core is an organic polymer or an inorganic material; L4 is a first linker or bond, L5 is a second linker, L6 is a third linker or bond, X3 and X4 are each independently a bond, alkylene, arylene, alkenylene, alkynylene, or any combination thereof; Each n1 is independently an integer of 0 to 200, Each n2 is independently an integer of 0 to 200, n1+n2≧1, m is an integer from 1 to 200, and the repeating units are the same or different; " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0091] In another embodiment, the antimicrobial group is [ka] (covalently bound to X3 or X4).

[0092] In some embodiments, antimicrobial particles comprising antimicrobially active units of structures (I), (IE) and (II)-(VII) have high thermal stability. Without being bound by any mechanism or theory, it is suggested that the high stability results from a lack or low number of available beta (β) hydrogens on the ammonium, thus reducing the likelihood of having a Hoffmann elimination, which in turn leads to reduced thermal stability.

[0093] In some embodiments, the terms "antimicrobial group" and "monomeric antimicrobial group" refer to the same thing and include quaternary ammonium and / or pyridinium, represented by the formula: [ka] During the ceremony, R4~R 11 and R4'~R 11 ' is as above.

[0094] In another embodiment, the number of antimicrobial groups per each unit of antimicrobial activity is at least 2, e.g., n1+n2≧1 and m≧1. In another embodiment, the number of antimicrobial groups per each unit of antimicrobial activity is 1, e.g., n1+n2=2 and m=1.

[0095] In another embodiment, the antimicrobially active units of structure (IE) comprise one monomer unit per antimicrobially active unit. In another embodiment, the antimicrobially active units of structures (I) and (II)-(VII) comprise one or more antimicrobial groups per antimicrobially active unit.

[0096] In another embodiment, the antimicrobially active units of structures (I), (IE) and (II)-(VII) have an inorganic core. In another embodiment, the antimicrobially active units of structures (I), (IE) and (II)-(VII) are connected to an organic core. In another embodiment, the organic core is a polymeric organic core. In another embodiment, the core is inert.

[0097] In one embodiment, Z1 is [ka] wherein X5 and R4 to R 11 are described below, with each possibility representing a separate embodiment of the present invention.

[0098] In one embodiment, Z2 is [ka] wherein X6 and R4 to R 11 are described below, with each possibility representing a separate embodiment of the present invention.

[0099] In one embodiment, R and / or R, R and / or R, and R and / or R are the same or different and are independently selected from methyl, CF, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof, where R is as described below. Each possibility represents a separate embodiment of the present invention.

[0100] In one embodiment, R and R are each independently absent, methyl, CF, perhaloalkyl, 2,2-disubstituted C-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, terpenoid moiety, cycloalkyl, aryl, phenyl, benzyl, heterocycle, conjugated alkyl, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof. Each possibility represents a separate embodiment of the present invention.

[0101] In one embodiment, R and / or R′, R and / or R′, R 10 and / or R 10 And R 11 and / or R 11' are the same or different and are independently H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl, or any combination thereof. Each possibility represents a separate embodiment of the present invention.

[0102] In one embodiment, X and / or X are the same or different and are independently a bond, alkylene, arylene, alkenylene, alkynylene, or any combination thereof. Each possibility represents a separate embodiment of the present invention.

[0103] In one embodiment, X5 and X6 are each independently a bond, -OC(=O)-, methylene, -OC(=O)-CH2-, 2,2-disubstituted C2-C 20 Alkylene, arylene, phenylene, benzylene, cycloalkylene, heterocycle, conjugated alkylene, terpenoid moiety, 1-alkenylene, 1-alkynylene, 2-alkenylene, 2-alkynylene, or any combination thereof. Each possibility represents a separate embodiment of the present invention.

[0104] In one embodiment, R is alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof. Each possibility represents a separate embodiment of the present invention.

[0105] In another embodiment, R4 and R4' are the same. In another embodiment, R5 and R5' are the same. In another embodiment, R6 and R6' are the same. In another embodiment, R7 and R7' are the same. In another embodiment, R8 and R8' are the same. In another embodiment, R9 and R9' are the same. In another embodiment, R 10 and R 10 In another embodiment, R 11 and R 11In another embodiment, X3 and X4 are the same. In another embodiment, X5 and X6 are the same. In another embodiment, R4 and R4' are different. In another embodiment, R5 and R5' are different. In another embodiment, R6 and R6' are different. In another embodiment, R7 and R7' are different. In another embodiment, R8 and R8' are different. In another embodiment, R9 and R9' are different. In another embodiment, R 10 and R 10 In another embodiment, R 11 and R 11 In another embodiment, X3 and X4 are different. In another embodiment, X5 and X6 are different.

[0106] In another embodiment, at least one of R4, R5 and R6, and / or at least one of R4', R5' and R6' of structure (I) is hydrophobic.

[0107] In another embodiment, R, R to R of structure (I) 11 and at least one of X5, and / or R6', R8' to R 11 At least one of X' and X6 is a terpenoid. Each possibility represents a separate embodiment of the present invention.

[0108] In one embodiment, n3 and n4 in structure (II) are each independently 0 or 1. Each possibility represents a separate embodiment of the present invention.

[0109] In some embodiments, L4, L5 or L6 are each independently the same or different linkers. In some embodiments, L4, L5 or L6 are linked to each other in any possible way. In some embodiments, L6 is nothing (or a bond) and L4 or L5 is covalently linked to the core. In another embodiment, L6 is covalently linked to the core and L4 or L5 is linked to L6. In another embodiment, L4 is linked to X3, L5 and L6 or to the core. In another embodiment, "linker" includes any possible chemical moiety that can link at least two other chemical moieties adjacent to such linker. In another embodiment, the monomeric unit of the antimicrobially active unit includes a first linker and / or a second linker (L4 or L5) and an antimicrobial group. In another embodiment, L4 and / or L5 are the backbone of the antimicrobially active unit (they are, for example, alkylene, polypeptide or oligosiloxane (-Si(OH)2-O- or -Si(CH3)2-O-) moieties). In some embodiments, the linker comprises a functional group. In another embodiment, the linker comprises two (the same or different) functional groups. In another embodiment, the functional group comprises a phosphate, a phosphonate, a siloxane, a silane, an ether, an acetal, a hydroxyl, an amide, an amine, an anhydride, an ester, a ketone, or one or more aromatic rings functionalized with any of the foregoing moieties. Each possibility represents a separate embodiment of the present invention.

[0110] In another embodiment, L4, L 5、 L 6、 X3, X4, X5, X6 or any combination thereof is a C1-C18 alkylene, alkenylene, alkynylene or aryl substituted with at least one carboxyl moiety, the carboxyl terminus being attached to a core, which is substituted with at least one carboxyl moiety and is capable of carrying an antibacterial group [- + N(R4)(R5)(R6)-, + N(R4')(R5')(R6'), [ka] The linker may be derived from a C1-C18 alkylene having an amino terminus modified to the amino terminus defined in structures (I) and (IE). The linker may be derived from an amino acid (polypeptide) of natural or synthetic origin having a chain length of 2 to 18 carbon atoms, or an acyl halide of said amino acid. Non-limiting examples of such amino acids are 18-aminooctadecanoic acid and 18-aminostearic acid. In another embodiment, L4, L5, L6, L7, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L18, L19, L20, L21, L22, L23, L24, L25, L26, L27, L28, L30, L31, L32, L41, L42, L43, L44, L45, L46, L47, L48, L49, L50, L51, L52, L53, L54, L55, L56, L57, L58, L59, L60, L61, L62, L63, L64, L65, L65, L66, L67, L68, L69, L70, L71, L72, L73, L74, L75, L76, L77, L78, L79, L81, L82, L83, L84, L85, L86, L87, L88, L89, L91, L92, L93, L94, L95, L96, L97, L98, L99, L100, L101, L112, L123, L134, L145, L151, L165, L176, L1 5、 L 6、 X3, X4, X5, X6 or any combination thereof is at least one amine, amide or pyridinium ( [ka] ) moiety.

[0111] In another embodiment, L4, L 5、 L 6、 X3, X4, X5, X6 or any combination thereof is a C1-C18 alkylene, alkenylene, alkynylene, arylene or aryl. The linker, each end of which is functionalized with a core and an antibacterial group, is a dihaloalkylene or dihaloarylene, which is substituted with a halogen moiety to attach to the core, and is substituted with a halogen moiety to attach to the core, as defined by structures (I)-(II)- + N(R4)(R5)(R6) or - + N(R4')(R5')(R6') can be derived by obtaining

[0112] In another embodiment, L4, L 5、 L 6、X3, X4, X5, X6 or any combination thereof are aromatic groups derived from non-limiting examples of 4,4-biphenol, dibenzoic acid, dibenzoic halide, dibenzoic sulfonate, terephthalic acid, tetrphthalic halide and terephthalic acid sulfonate. The linker is functionalized with the core and antibacterial group through its functional group (e.g., hydroxyl, carboxy or sulfonate), respectively. In another embodiment, the linker is attached to the core directly at one end or indirectly through a third linker (L6) and to the antibacterial group [- + N(R4)(R5)(R6)-, + N(R4')(R5')(R6'), [ka] The structure has been modified to the structure defined in (I) to (IE).

[0113] In another embodiment, L4, L 5、 L 6、 X3, X4, X5, X6 or any combination thereof is a siloxane or silane group derived and / or selected from the non-limiting examples of trialkoxyalkylsilane, trialkoxyarylsilane, trihaloalkylsilane, trihaloarylsilane, 3-aminopropyltriethoxysilane (APTES), (3-glycidyloxypropyl)trimethoxysilane and N-2-aminoethyl-3-aminopropyltrimethoxysilane. The linker is functionalized with the core and antibacterial group through its functional group (e.g., hydroxyl, siloxane, carboxy, amide or sulfonate), respectively. In another embodiment, the linker is attached to the core directly at one end or indirectly through a third linker (L6) and to the antibacterial group [- + N(R4)(R5)(R6)-, + N(R4')(R5')(R6'), [ka] The structure has been modified to the structure defined in (I) to (IE).

[0114] The linker is functionalized with the core and antimicrobial groups through its functional groups (e.g., hydroxyl, siloxane, carboxy, amide or sulfonate), respectively. In another embodiment, the linker is attached to the core directly at one end or indirectly through a third linker (L6) and to the antimicrobial activity [- + N(R4)(R5)(R6)-, + N(R4')(R5')(R6'), [ka] The structure has been modified to the structure defined in (I) to (IE).

[0115] In another embodiment, the monomer units within the antimicrobially active units of the invention (e.g., as depicted in Figures 2A-2B and formulae IE and I-VII) have the structure of formula IF1 or IF2. [ka] is represented by R4 and R5 are independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R6 is methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C 20alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, a terpenoid moiety, cycloalkyl, aryl, phenyl, benzyl, heterocycle, conjugated alkyl, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R is alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof; q is an integer from 0 to 16, The monomer units are chemically bound to the surface of the inorganic core either directly or via a third linker (L6).

[0116] In another embodiment, the monomer units within the antimicrobially active units of the present invention (e.g., as depicted in Figures 2A-2B and Formulae IE and I-VII) have the structure of formula IG1 or IG2: [ka] wherein: R4 to R6 are as described above. q and q 1 are independently an integer from 0 to 16, The monomer units are chemically bound to the surface of the inorganic core either directly or via a third linker (L6).

[0117] In another embodiment, the linker molecule that can be used in the process of preparing the antimicrobial particles of the present invention has the structure of formula IH1 or IH2. [ka] wherein: Q 201 , Q 202 and Q 203is independently selected from the group consisting of alkoxy, methyl, ethyl, hydrogen, sulfonate and halide; Q 201 , Q 202 and Q 203 is selected from ethoxy, methoxy, sulfonate (e.g., mesyl, tosyl) and halide; q is an integer from 0 to 16, The linker molecule can be chemically bonded to the surface of the inorganic core via a silicon atom; The antimicrobial groups are introduced by functionalizing primary amines to give antimicrobially active quaternary ammonium groups, as described above.

[0118] In another embodiment, a linker molecule that may be used in the process of preparing the antimicrobial particles of the present invention has the structure of formula IJ: [ka] wherein: Q 201 , Q 202 and Q 203 is independently selected from the group consisting of alkoxy, methyl, ethyl, hydrogen, sulfonate and halide; Q 201 , Q 202 and Q 203 is selected from ethoxy, methoxy, sulfonate (e.g., mesyl, tosyl) and halide; W1 is selected from the group consisting of arylene-NH2, benzylene-NH2, halide, sulfonate and hydroxyl; q is an integer from 0 to 16; the linker is capable of chemically bonding to the surface of the inorganic core via a silicon atom; The antibacterial group is introduced by substituting or converting group W into an antibacterial group.

[0119] Antibacterial group containing one long alkyl group.

[0120] In one embodiment, the antimicrobial group of the present invention is the antimicrobial group [ [ka] R8 to R1 of the structures (I) and (IE) 11 and / or R8'~R 11 ' includes one alkyl group having 4 to 24 carbon atoms.

[0121] The term "quaternary ammonium group" refers to a group of atoms consisting of a nitrogen atom having four substituents (other than hydrogen) attached thereto. In another embodiment, "quaternary ammonium group" refers to a group of atoms consisting of a nitrogen atom having four groups, each group attached to the nitrogen through a carbon atom. The term "long alkyl group" or chain refers to such alkyl groups or chains, found either substituted on the nitrogen atom of a quaternary ammonium group or as a substituent to a pyridinium, having from 4 to 24 carbon atoms. In some embodiments, the alkyl group is an alkyl group having from 4 to 18 carbon atoms. In some embodiments, the alkyl group is an alkyl group having from 4 to 8 carbon atoms. In some embodiments, the alkyl group is an alkyl group having from 4 to 10 carbon atoms. In other embodiments, the alkyl group is an alkyl group having 6, 7, or 8 carbon atoms, with each possibility representing a separate embodiment of the present invention.

[0122] Polymerizable Unit In some embodiments, the polymerizable unit has Structure (7): [ka] wherein: L7 is a first linker or bond, L8 is a third linker or bond, X7 is a bond, alkylene, arylene, alkenylene, alkynylene, or any combination thereof; X8 is nothing or hydrogen; Z3 is a functional polymerizable group or multiple functional polymerizable groups with a linker therebetween, each functional polymerizable group being independently selected from the group consisting essentially of substituted or unsubstituted acrylate, substituted or unsubstituted epoxy, substituted or unsubstituted vinyl, or isocyanate moieties, each substituent being alkyl, alkoxy, haloalkyl, halide, cycloalkyl, aryl, heterocycle, or C(=O)O(alkyl); " [ka] The term "covalent bonding" refers to a covalent bond to an organic or inorganic core.

[0123] In certain embodiments, a non-limiting example of an optionally substituted epoxy group of Z3 includes 3-glycidyloxypropyl.

[0124] Non-limiting examples of vinyl groups for Z3 include unsubstituted or substituted vinyl.

[0125] In another embodiment, Z3 is -OC(O)-CH=CH2 (acrylate); -OC(O)-C(CH3)=CH2 (methacrylate); [ka] (epoxy); -CH=CH2 (vinyl) or -N=C=O (isocyanate). In another embodiment, Z3 is multiple functional polymerizable groups connected with a linker between them. In yet another embodiment, Z3 is -(CH=CH) 1-6 -CH=CH2 (oligoacetylene; or [ka] (pentaerythritol triacrylate).

[0126] In another embodiment, the polymerizable unit is Si-alkylene-OC(O)-CH=CH2 (Si-acrylate); [ka] (Si-epoxy); Si-alkylene-CH=CH2 (Si-vinyl); Si-CH=CH2 (Si-direct-vinyl), Si-alkylene-N=C=O (Si-isocyanate), {N}-Alkylene-OC(O)-CH=CH2 (N-acrylate); [ka] (N-epoxy);{N}-alkylene-CH=CH2 (N-vinyl), {N}-CH=CH2 (N-direct-vinyl), or {N}-alkylene-N=C=O (N-isocyanate), where "alkylene" may contain an ether oxygen (epoxy moiety), for example 3-glycidyloxypropyl, "Si" is part of a siloxane moiety directly connected to the core, and "{N}" is a nitrogen (containing nitrogen atom) linker, for example, amide, amine, guanidine, imidazole, etc.

[0127] A non-limiting example of an epoxy group of the polymerizable unit that may be substituted in certain embodiments includes 3-glycidyloxypropyl.

[0128] In one embodiment, X7 is a bond, alkylene, arylene, alkenylene, alkynylene, or any combination thereof. Each possibility represents a separate embodiment of the present invention.

[0129] In one embodiment, X8 is nothing or hydrogen. Each possibility represents a separate embodiment of the present invention.

[0130] In some embodiments of the polymerizable unit, L7 or L8 are each independently the same linker or different linkers. In some embodiments, L7 or L8 are bonded to each other in any possible way. In some embodiments, L8 is nothing (or a bond) and L7 is covalently bonded to the core. In another embodiment, L8 is covalently bonded to the core and L7 is bonded to L8. In another embodiment, L7 is bonded to X7, X8 and L8 or to the core. In another embodiment, the "linker" includes any possible chemical moiety that can link at least two other chemical moieties adjacent to such a linker. In another embodiment, the linker includes a functional group. In another embodiment, the linker includes two (same or different) functional groups. In another embodiment, the functional group includes a phosphate, a phosphonate, a siloxane, a silane, an ether acetal, an amide, an amine, an anhydride, an ester, a ketone, or one or more aromatic rings functionalized with any of the aforementioned moieties. Each possibility represents a separate embodiment of the invention.

[0131] In another embodiment, the monomer unit of the polymerizable unit comprises a first linker and / or a second linker (L7 or L8) and a functional polymerizable group. In another embodiment, L7 and / or L8 are the backbone of the polymerizable unit (they are, for example, alkylene, polypeptide or oligosiloxane (-Si(OH)2-O- or -Si(CH3)2-O-) moieties). In some embodiments, the linker comprises a functional group. In another embodiment, the linker comprises two (the same or different) functional groups. In another embodiment, the functional group comprises a phosphate, phosphonate, siloxane, silane, ether, acetal, hydroxyl, amide, amine, anhydride, ester, ketone, or one or more aromatic rings functionalized with any of the aforementioned moieties. Each possibility represents a separate embodiment of the present invention.

[0132] In another embodiment, L7, L 8、X7, X8 or any combination thereof is a C1-C18 alkylene, alkenylene, alkynylene or aryl substituted with at least one carboxyl moiety, the carboxyl terminus being attached to the core. It may be derived from a C1-C18 alkylene substituted with at least one carboxyl moiety and having an amino terminus functionalized with, for example, an alkylene, terminated with an epoxy, acrylate, isocyanate or vinyl. This linker may be derived from an amino acid (polypeptide) of natural or synthetic origin having a chain length of 2 to 18 carbon atoms, or an acyl halide of said amino acid. Non-limiting examples of such amino acids are 18-aminooctadecanoic acid and 18-aminostearic acid.

[0133] In another embodiment, L7, L 8、 X7, X8 or any combination thereof is a C1-C18 alkylene, alkenylene, alkynylene, arylene or aryl. This linker, each end of which is functionalized with a core and a functional polymerizable group, can be derived from a dihaloalkylene or dihaloarylene by substituting a halogen moiety with a functional group that bonds to the core, and substituting the halogen moiety to provide an epoxy, acrylate, isocyanate or vinyl moiety.

[0134] In another embodiment, L7, L 8、 X7, X8 or any combination thereof are aromatic groups derived from non-limiting examples of 4,4-biphenol, dibenzoic acid, dibenzoic halide, dibenzoic sulfonate, terephthalic acid, tetrphthalic halide and terephthalic acid sulfonate. The linker is functionalized with the core and functional polymerizable group through the functional group (e.g., hydroxyl, carboxy or sulfonate) of the aromatic group mentioned herein, respectively.

[0135] In another embodiment, L7, L 8、X7, X8 or any combination thereof is a siloxane or silane group derived and / or selected from the non-limiting examples of trialkoxyalkylsilane, trialkoxyarylsilane, trihaloalkylsilane, trihaloarylsilane, 3-aminopropyltriethoxysilane (APTES), (3-glycidyloxypropyl)trimethoxysilane and N-2-aminoethyl-3-aminopropyltrimethoxysilane. The linker is functionalized with the core and functional polymerizable group through its functional group (e.g., hydroxyl, siloxane, carboxy, amide or sulfonate), respectively.

[0136] General definition of the particles of the present invention In some embodiments, the antimicrobial units within the antimicrobial particles of the invention comprise tertiary amine or tertiary ammonium; or quaternary ammonium and / or pyridinium containing antimicrobial groups represented by the following formulas: - + N(R1)(R2)(R3), - + N(R1)(R2)-,- + NH(R1)(R2), - + NH(R1)-, -N(R1)(R2), -N(R1)-, - + N(R1')(R2')(R3'), - + N(R1')(R2')-, - + NH(R1')(R2'), - + NH(R1')-, -N(R1')(R2'), -N(R1')-, [ka] During the ceremony, R1~R 11 and R1'~R 11 ' is as above.

[0137] In another embodiment, the activity of the quaternary ammonium, tertiary amine or tertiary ammonium or pyridinium remains strong at any pH.

[0138] In some embodiments, the polymerizable units in the antimicrobial particles of the present invention are Si-alkylene-OC(O)-CH=CH2 (Si-acrylate); [ka] (Si-epoxy); Si-alkylene-CH=CH2 (Si-vinyl); Si-alkylene-N=C=O (Si-isocyanate), {N}-Alkylene-OC(O)-CH=CH2 (N-acrylate); [ka] (N-epoxy);{N}-alkylene-CH=CH2 (N-vinyl) or {N}-alkylene-N=C=O (N-isocyanate), where "Si" is part of a siloxane moiety directly attached to the core and "{N}" is a nitrogen (containing a nitrogen atom) linker, such as amide, amine, guanidine, imidazole, etc.

[0139] As used herein, the term "alkyl" or "alkylene," unless otherwise specified, refers to any straight or branched chain alkyl group containing up to about 24 carbons. In one embodiment, an alkyl contains C1-C3 carbons. In one embodiment, an alkyl contains C1-C4 carbons. In one embodiment, an alkyl contains C1-C5 carbons. In another embodiment, an alkyl contains C1-C6 carbons. In another embodiment, an alkyl contains C1-C8 carbons. In another embodiment, an alkyl contains C1-C 10 In another embodiment, alkyl is C-C 12 In another embodiment, the alkyl comprises C4-C8 carbons. In another embodiment, the alkyl comprises C4-C 10 In another embodiment, alkyl is C4-C 18 In another embodiment, alkyl is C4-C 24 In another embodiment, alkyl is C-C 18 In another embodiment, alkyl is C-C 18In another embodiment, the branched alkyl is an alkyl substituted with an alkyl side chain of 1 to 5 carbons. In one embodiment, the alkyl group may be unsubstituted. In another embodiment, the alkyl group may be substituted with halogen, haloalkyl, hydroxyl, alkoxy, carbonyl, amido, alkylamido, dialkylamido, cyano, nitro, CO2H, amino, alkylamino, dialkylamino, carboxyl, thio and / or thioalkyl. In another embodiment, the alkyl is substituted with 2,2-disubstituted C3-C 20 Alkyl. 2,2-disubstituted C3-C 20 The term "alkyl" refers to an alkyl as described herein having 3-20 carbons and substituted three times at the second carbon (from the point of attachment) with halogen, haloalkyl, alkyl, alkoxy, carbonyl, amido, alkylamido, dialkylamido, cyano, nitro, CO2H, amino, alkylamino, dialkylamino, carboxyl, thio and / or thioalkyl, such substitutions may be the same or different, or it is substituted once at the second carbon with oxo (=O) or other double bond to an element (e.g., S) or moiety (e.g., vinyl carbon or NH) and further substituted with a substituent selected from the above list of first possibilities. In all cases, there is no hydrogen available for abstraction at this second carbon position (e.g., no hydrogen is found at this position, only non-hydrogen substituents are found). 2,2-disubstituted C3-C 20 Non-limiting examples of alkyl include neopentyl (-CH2-C(CH3)3, -CH2-C(CH3)2-CH2CH3, CH2-CF2CH3, and -CH2C(=O)CH3. In another embodiment, alkyl is a 2,2-disubstituted C3-C8 alkyl. In another embodiment, alkyl is a 2,2-disubstituted C3-C8 alkyl. 10 In another embodiment, the alkyl is a 2,2-disubstituted C-C 12 In another embodiment, the alkyl is a 2,2-disubstituted C-C 18 "2,2-disubstituted C3-C8 alkyl", "2,2-disubstituted C3-C 10Alkyl, 2,2-disubstituted C3-C 12 Alkyl" and "2,2-disubstituted C3-C 18 The term "alkyl" refers to "2,2-disubstituted C3-C 20 The term refers to a moiety similar to "alkyl", but it is used to refer to C3-C8 and C3-C 10 , C3-C 12 and C3-C 18 In another embodiment, the alkylene is a 2,2-disubstituted C-C 20 Alkylene. "2,2-disubstituted C2-C 20 The term alkylene refers to 2,2-disubstituted C 20 refers to moieties similar to "alkyl" but including alkylenes as defined herein having 2 to 20 carbons. 20 Non-limiting examples of alkylene include neopentylene (-CH-C(CH)-CH-, -CH-C(CH)-CHCH-, -CH-CFCH-, and -CHC(=O)CH-. In another embodiment, alkylene is a 2,2-disubstituted C-C alkylene. In another embodiment, alkylene is a 2,2-disubstituted C-C 10 In another embodiment, the alkylene is a 2,2-disubstituted C-C 12 In another embodiment, the alkylene is a 2,2-disubstituted C-C 18 Alkylene. "2,2-disubstituted C2-C8 alkylene", "2,2-disubstituted C2-C 10 alkylene", "2,2-disubstituted C2-C 12 Alkylene" and "2,2-disubstituted C2-C 18 The term alkylene refers to 2,2-disubstituted C 20 The term refers to a moiety similar to "alkylene", but it is C2-C8 and C2-C 10 , C2-C 12 and C2-C 18 Contains alkylene.

[0140] In another embodiment, the alkyl is 2,2,2-trisubstituted ethyl. The term "2,2,2-trisubstituted ethyl" refers to an ethyl substituted three times at the second carbon (from the point of attachment) with halogen, haloalkyl, alkoxy, carbonyl, amido, alkylamido, dialkylamido, cyano, nitro, CO2H, amino, alkylamino, dialkylamino, carboxyl, thio and / or thioalkyl, such substitutions may be the same or different, or it is substituted once at the second carbon with oxo (=O) or other double bond to an element (e.g., S) or moiety (e.g., vinyl carbon or NH) and further substituted with a substituent selected from the above list of first possibilities. In all cases, there is no hydrogen available for abstraction at this second carbon position (e.g., no hydrogen is found at this position, only non-hydrogen substituents are found). Non-limiting examples of 2,2,2-trisubstituted ethyl include 2,2,2-trihaloethyl and -CH2C(=O)-NH2. In another embodiment, hydrophobic alkyl refers to an alkyl having at least 4 carbons. In another embodiment, hydrophobic alkyl refers to an alkyl having at least 4 carbons. 24 In another embodiment, the hydrophobic alkyl refers to a C4-C8 alkyl. In another embodiment, the hydrophobic alkyl refers to a C4 alkyl. In another embodiment, the hydrophobic alkyl refers to a C5 alkyl. In another embodiment, the hydrophobic alkyl refers to a C6 alkyl. In another embodiment, the hydrophobic alkyl refers to a C7 alkyl. In another embodiment, the hydrophobic alkyl refers to a C8 alkyl.

[0141] As used herein, the term "aryl" refers to any aromatic ring that is directly bonded to another group and may be substituted or unsubstituted. As used herein, the term "arylene" refers to something that is directly bonded to two groups (e.g., an arylene is, for example, phenylene, -CH-). In another embodiment, it can be directly bonded to three or more groups. An aryl or arylene group may be the sole substituent or may be a component of a larger substituent, such as an arylalkyl, arylamino, arylamide, etc. Exemplary aryl (as well as arylene) groups include, but are not limited to, phenyl, tolyl, xylyl, furanyl, naphthyl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, thiophen-yl, pyrrolyl, phenylmethyl, phenylethyl, phenylamino, phenylamide, etc. Substitutions include, but are not limited to, F, Cl, Br, I, C1-C5 straight or branched alkyl, C1-C5 straight or branched haloalkyl, C1-C5 straight or branched alkyl or alkoxy, C1-C5 straight or branched haloalkyl or haloalkoxy, CF3, CN, NO2, -CH2CN, NH2, NH-alkyl, N(alkyl)2, hydroxyl, -OC(O)CF3, -OCH2Ph, -NHCO-alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, or -C(O)NH2. In another embodiment, hydrophobic aryl or arylene refers to an aryl or arylene having at least 6 carbons.

[0142] As used herein, the term "benzyl" refers to a -CH2-CH5 moiety, which may be unsubstituted or substituted with the following non-limiting list of substituents: F, Cl, Br, I, C1-C5 straight or branched alkyl, C1-C5 straight or branched haloalkyl, C1-C5 straight or branched alkyl or alkoxy, C1-C5 straight or branched haloalkyl or haloalkoxy, CF3, CN, NO2, -CH2CN, NH2, NH-alkyl, N(alkyl)2, hydroxyl, -OC(O)CF3, -OCH2Ph, -NHCO-alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, or -C(O)NH2. Similarly, "benzylene" refers to a -CH2-CH4- moiety, which may be unsubstituted or substituted with the substituents listed above for a benzyl moiety.

[0143] As used herein, the term "haloalkyl" refers to an alkyl as described herein above and substituted at least once with a halide (e.g., F, Cl, Br, or I). In one embodiment, all alkyls are substituted with halides, e.g., no hydrogen is found in the haloalkyl, and are referred to as "perhaloalkyls" (e.g., CF3: perfluoromethyl or CCl3: perchloromethyl). In one embodiment, only a portion of the alkyl is substituted with a halide (e.g., CH2CF3). In another embodiment, non-limiting examples of haloalkyls include CF3, CCl3, CH2CF3, CF2CF3, CCl2CCl3, and CI3.

[0144] The term "alkenyl" or "alkenylene" refers to a substance that contains at least two carbon atoms and at least one double bond. The terms "1-alkenyl" or "1-alkenylene" refer to the same thing, with the double bond on the first carbon (from the point of attachment). The terms "2-alkenyl" or "2-alkenylene" refer to the same thing, with the double bond on the second carbon (from the point of attachment). The terms "3-alkenyl" or "3-alkenylene" refer to the same thing, with the double bond on the third carbon (from the point of attachment). In one embodiment, an alkenyl has 2-7 carbon atoms. In one embodiment, an alkenyl has 2-12 carbon atoms. In one embodiment, an alkenyl has 2-10 carbon atoms. In one embodiment, an alkenyl has 3-6 carbon atoms. In one embodiment, an alkenyl has 2-4 carbon atoms. In one embodiment, an alkenyl has 4-8 carbon atoms. In another embodiment, a hydrophobic alkenyl refers to an alkenyl having at least 4 carbons. In another embodiment, hydrophobic alkenyl refers to a C4-C8 alkenyl.

[0145] The term "alkynyl" or "alkynylene" refers to a substance containing at least two carbon atoms and at least one triple bond. The terms "1-alkynyl" or "1-alkynylene" refer to the same thing, where the triple bond is on the first carbon (from the point of attachment). The terms "2-alkynyl" or "2-alkynylene" refer to the same thing, where the triple bond is on the second carbon (from the point of attachment). The terms "3-alkynyl" or "3-alkynylene" refer to the same thing, where the triple bond is on the third carbon (from the point of attachment). In one embodiment, an alkynyl has 2-7 carbon atoms. In another embodiment, an alkynyl has 2-12 carbon atoms. In another embodiment, an alkynyl has 2-10 carbon atoms. In another embodiment, an alkynyl has 3-6 carbon atoms. In another embodiment, an alkynyl has 2-4 carbon atoms. In another embodiment, an alkynyl has 3-6 carbon atoms. In another embodiment, an alkynyl has 4-8 carbon atoms. In another embodiment, hydrophobic alkynyl refers to an alkynyl having at least 4 carbons. In another embodiment, hydrophobic alkynyl refers to a C4-C8 alkynyl.

[0146] The term "alkoxy" in one embodiment refers to an alkyl, as defined above, attached to an oxygen. Non-limiting examples of alkoxy groups include methoxy, ethoxy and isopropoxy.

[0147] A "cycloalkyl" group, in one embodiment, refers to a ring structure that contains carbon atoms as ring atoms, and may be saturated or unsaturated, substituted or unsubstituted, and is directly bonded to a group (e.g., cyclohexyl-, CH 11-). In another embodiment, the cycloalkyl is a 3-12 membered ring. In another embodiment, the cycloalkyl is a 6 membered ring. In another embodiment, the cycloalkyl is a 5-7 membered ring. In another embodiment, the cycloalkyl is a 3-8 membered ring. In another embodiment, the cycloalkyl group can be unsubstituted or substituted with halogen, alkyl, haloalkyl, hydroxyl, alkoxy, carbonyl, amido, alkylamido, dialkylamido, cyano, nitro, CO2H, amino, alkylamino, dialkylamino, carboxyl, thio and / or thioalkyl. In another embodiment, the cycloalkyl ring can be fused to another saturated or unsaturated cycloalkyl or heterocyclic 3-8 membered ring. In another embodiment, the cycloalkyl ring is a saturated ring. In another embodiment, the cycloalkyl ring is an unsaturated ring. Non-limiting examples of cycloalkyl groups include cyclohexyl, cyclohexenyl, cyclopropyl, cyclopropenyl, cyclopentyl, cyclopentenyl, cyclobutyl, cyclobutenyl, cyclooctyl, cyclooctadienyl (COD), cyclooctaene (COE), and the like. In another embodiment, hydrophobic cycloalkyl refers to a cycloalkyl having at least six carbons. A "cycloalkylene" group, in one embodiment, refers to the same definition as above for "cycloalkyl," except that the cycloalkylene is directly bonded to two groups (e.g., -cyclohexylene-, -CH 10 In another embodiment, it is directly bonded to three or more groups.

[0148] A "heterocyclic" group, in one embodiment, refers to a ring structure that includes, in addition to carbon atoms, sulfur, oxygen, nitrogen, or any combination thereof, as part of the ring. In another embodiment, the heterocyclic ring is a 3-12 membered ring. In another embodiment, the heterocyclic ring is a 6 membered ring. In another embodiment, the heterocyclic ring is a 5-7 membered ring. In another embodiment, the heterocyclic ring is a 3-8 membered ring. In another embodiment, the heterocyclic group can be unsubstituted or substituted with halogen, alkyl, haloalkyl, hydroxyl, alkoxy, carbonyl, amido, alkylamido, dialkylamido, cyano, nitro, COH, amino, alkylamino, dialkylamino, carboxyl, thio, and / or thioalkyl. In another embodiment, the heterocyclic ring can be fused to another saturated or unsaturated cycloalkyl or heterocyclic 3-8 membered ring. In another embodiment, the heterocyclic ring is a saturated ring. In another embodiment, the heterocyclic ring is an unsaturated ring. Non-limiting examples of heterocyclic rings include pyridine, piperidine, morpholine, piperazine, thiophene, pyrrole, benzodioxole, or indole. In another embodiment, the hydrophobic heterocyclic group refers to a heterocycle having at least 6 carbons. In one embodiment, the heterocycle is directly bonded to a group (e.g., pyridinyl, [ka] In one embodiment, the heterocycle is directly bonded to two groups (e.g., pyridinylene, [ka] In one embodiment, the heterocycle is directly bonded to three or more groups.

[0149] The term "hydrophobic" refers to an alkyl, alkenyl, or alkynyl having at least 4 carbons, or the term hydrophobic refers to a terpenoid, cycloalkyl, aryl, or heterocycle having at least 6 carbons. Each possibility represents a separate embodiment of the present invention.

[0150] The antimicrobial groups of the present invention (e.g., of all antimicrobially active units, see sections "A)" to "C)" above) are chemically attached to the core at a surface density of at least 1 antimicrobial group per 10 sq. nm of core surface. In another embodiment, at least 1 antimicrobial group per sq nm of core surface. In another embodiment, 0.001-300 antimicrobial groups per sq nm of core surface. In another embodiment, 0.001-250 antimicrobial groups per sq nm of core surface. In another embodiment, 0.001-200 antimicrobial groups per sq nm of core surface. In another embodiment, 0.001-150 antimicrobial groups per sq nm of core surface. In another embodiment, 0.001-100 antimicrobial groups per sq nm of core surface. In another embodiment, 0.001-50 antimicrobial groups per sq nm of core surface. In another embodiment, 0.001-20 antimicrobial groups per sq nm of core surface. In another embodiment, there are 0.001-17 antimicrobial groups per sq nm of the core surface. In another embodiment, there are 0.001-15 antimicrobial groups per sq nm of the core surface. In another embodiment, there are 0.001-10 antimicrobial groups per sq nm of the core surface. In another embodiment, there are 0.001-4 antimicrobial groups per sq nm of the core surface. In another embodiment, there are 0.001-1 antimicrobial groups per sq nm of the core surface. In another embodiment, there are 50-100 antimicrobial groups per sq nm of the core surface. In another embodiment, there are 100-150 antimicrobial groups per sq nm of the core surface. In another embodiment, there are 150-200 antimicrobial groups per sq nm of the core surface. In another embodiment, there are 200-250 antimicrobial groups per sq nm of the core surface. In another embodiment, there are 250-300 antimicrobial groups per sq nm of the core surface. In another embodiment, there are 1 to 4 antimicrobial groups per sq nm of core surface. In another embodiment, there are 1 to 6 antimicrobial groups per sq nm of core surface. In another embodiment, there are 1 to 20 antimicrobial groups per sq nm of core surface. In another embodiment, there are 1 to 10 antimicrobial groups per sq nm of core surface. In another embodiment, there are 1 to 15 antimicrobial groups per sq nm of core surface. Each possibility represents a separate embodiment of the present invention.

[0151] In some embodiments, the number of antimicrobial groups [(n1+n2×m]] per each unit of antimicrobial activity (e.g., as shown in Sections "A)"-"C") above) is 1-200. In another embodiment, the number of antimicrobial groups per each unit of antimicrobial activity is 1-150. In another embodiment, the number of antimicrobial groups per each unit of antimicrobial activity is 1-100. In another embodiment, the number of antimicrobial groups per each unit of antimicrobial activity is 1-50. In another embodiment, the number of antimicrobial groups per each unit of antimicrobial activity is 1-30. In another embodiment, the number of antimicrobial groups per each unit of antimicrobial activity is 1-20. In another embodiment, the number of antimicrobial groups per each unit of antimicrobial activity is 1-10. In another embodiment, the number of antimicrobial groups per each unit of antimicrobial activity is 50-100. In another embodiment, the number of antimicrobial groups per each unit of antimicrobial activity is 100-150. In another embodiment, the number of antimicrobial activity units per each unit of antimicrobial activity is 150-200. Each possibility represents a separate embodiment of the present invention.

[0152] In some embodiments, the number of monomer units per each unit of antimicrobial activity (e.g., as shown in Sections "A)" through "C") above) is between 1 and 200. In another embodiment, the number of monomer units per each unit of antimicrobial activity is between 1 and 150. In another embodiment, the number of monomer units per each unit of antimicrobial activity is between 1 and 100. In another embodiment, the number of monomer units per each unit of antimicrobial activity is between 1 and 50. In another embodiment, the number of monomer units per each unit of antimicrobial activity is between 1 and 30. In another embodiment, the number of monomer units per each unit of antimicrobial activity is between 1 and 20. In another embodiment, the number of monomer units per each unit of antimicrobial activity is between 1 and 10. In another embodiment, the number of monomer units per each unit of antimicrobial activity is between 50 and 100. In another embodiment, the number of monomer units per each unit of antimicrobial activity is between 100 and 150. In another embodiment, the number of monomer units per each unit of antimicrobial activity is between 150 and 200. Each possibility represents a separate embodiment of the present invention.

[0153] In one embodiment, n1 is 0 to 200. In another embodiment, n1 is 0 to 10. In another embodiment, n1 is 10 to 20. In another embodiment, n1 is 20 to 30. In another embodiment, n1 is 30 to 40. In another embodiment, n1 is 40 to 50. In another embodiment, n1 is 50 to 60. In another embodiment, n1 is 60 to 70. In another embodiment, n1 is 70 to 80. In another embodiment, n1 is 80 to 90. In another embodiment, n1 is 90 to 100. In another embodiment, n1 is 100 to 110. In another embodiment, n1 is 110 to 120. In another embodiment, n1 is 120 to 130. In another embodiment, n1 is 130 to 140. In another embodiment, n1 is 140 to 150. In another embodiment, n1 is 150 to 160. In another embodiment, n1 is 160 to 170. In another embodiment, n1 is 170 to 180. In another embodiment, n1 is 180 to 190. In another embodiment, n1 is 190 to 200. Each possibility represents a separate embodiment of the present invention.

[0154] In one embodiment, n2 is 0 to 200. In another embodiment, n2 is 0 to 10. In another embodiment, n2 is 10 to 20. In another embodiment, n2 is 20 to 30. In another embodiment, n2 is 30 to 40. In another embodiment, n2 is 40 to 50. In another embodiment, n2 is 50 to 60. In another embodiment, n2 is 60 to 70. In another embodiment, n2 is 70 to 80. In another embodiment, n2 is 80 to 90. In another embodiment, n2 is 90 to 100. In another embodiment, n2 is 100 to 110. In another embodiment, n2 is 110 to 120. In another embodiment, n2 is 120 to 130. In another embodiment, n2 is 130 to 140. In another embodiment, n2 is 140 to 150. In another embodiment, n2 is 150 to 160. In another embodiment, n2 is 160 to 170. In another embodiment, n2 is 170 to 180. In another embodiment, n2 is 180 to 190. In another embodiment, n2 is 190 to 200. Each possibility represents a separate embodiment of the present invention.

[0155] In one embodiment, m is 1 to 200. In another embodiment, m is 1 to 10. In another embodiment, m is 10 to 20. In another embodiment, m is 20 to 30. In another embodiment, m is 30 to 40. In another embodiment, m is 40 to 50. In another embodiment, m is 50 to 60. In another embodiment, m is 60 to 70. In another embodiment, m is 70 to 80. In another embodiment, m is 80 to 90. In another embodiment, m is 90 to 100. In another embodiment, m is 100 to 110. In another embodiment, m is 110 to 120. In another embodiment, m is 120 to 130. In another embodiment, m is 130 to 140. In another embodiment, m is 140 to 150. In another embodiment, m is 150 to 160. In another embodiment, m is 160 to 170. In another embodiment, m is 170 to 180. In another embodiment, m is from 180 to 190. In another embodiment, m is from 190 to 200. Each possibility represents a separate embodiment of the present invention.

[0156] In another embodiment, the antimicrobial groups of the present invention may be selected from (a) a quaternary ammonium group comprising at least one terpenoid moiety or one hydrophobic group; and (b) a pyridinium group. Each possibility represents a separate embodiment of the present invention.

[0157] As used herein, the term "nanoparticle" refers to a particle having a diameter of less than about 1,000 nm. As used herein, the term "microparticle" refers to a particle having a diameter of about 1,000 nm or greater.

[0158] The antimicrobial particles of the present invention are characterized by having a diameter of about 5 to about 100,000 nm, and thus encompass both nanoparticle and microparticle compositions. For example, the particles may be about 10 to about 50,000 nm. In other embodiments, the particles are greater than 1,000 nm in diameter. In other embodiments, the particles are greater than 10,000 nm in diameter. In other embodiments, the particles are 1,000 to 50,000 nm in diameter. In other embodiments, the particles are 5 to 250 nm in diameter. In other embodiments, the particles are 5 to 500 nm in diameter. In another embodiment, the particles are 5 to 1000 nm in diameter. It will be apparent to one of ordinary skill in the art that other particle size ranges are applicable and are encompassed within the scope of the present invention.

[0159] The antimicrobial group of the present invention can be in the form of quaternary ammonium salt or pyridinium salt as described above.Since all such groups are positively charged, their charge is balanced by an anion.Non-limiting examples of anions include halides, such as fluoride, chloride, bromide or iodide, and fluoride, bicarbonate, nitrate, phosphate, acetate, fumarate, succinate, mesylate, triflate, tosylate, tetrafluoroborate, hexafluorophosphate and sulfate.Each possibility represents a separate embodiment of the present invention.

[0160] In some embodiments, the term "quaternary ammonium group" refers to a group of atoms consisting of a nitrogen atom having four substituents (other than hydrogen) attached thereto. In another embodiment, "quaternary ammonium group" refers to a group of atoms consisting of a nitrogen atom having four groups, each group attached to the nitrogen through a carbon atom. In some embodiments, the quaternary ammonium groups provided herein comprise at least one long alkyl chain. In some embodiments, the quaternary ammonium groups provided herein comprise at least one terpenoid. The term "long alkyl group" or chain refers to such an alkyl group or chain substituted on the nitrogen atom of the quaternary ammonium group and having 4 to 24 carbon atoms. In some embodiments, the alkyl group is an alkyl group having 4 to 18 carbon atoms. In some embodiments, the alkyl group is an alkyl group having 4 to 8 carbon atoms. In some embodiments, the alkyl group is an alkyl group having 4 to 10 carbon atoms. In other embodiments, the alkyl group is an alkyl group having 6, 7, or 8 carbon atoms, each possibility representing a separate embodiment of the invention.

[0161] Antibacterial groups containing terpenoid groups In one embodiment, the antimicrobial group of the present invention comprises at least one terpenoid group, as described above with respect to the antimicrobial particles and their antimicrobially active units (e.g., formulas (1)-(6), (I)-(VII), (IA)-(IE), (IF1)-(IF2), (IG1)-(IG2), (I1)-(IH2) and IJ). In another embodiment, the antimicrobial group is selected from (a) a tertiary amine (R3 and / or R3' are nothing) or tertiary ammonium (R3 and / or R3' are H) comprising at least one terpenoid moiety; and (b) a quaternary ammonium group comprising at least one terpenoid moiety. In another embodiment, when the antimicrobial group of the present invention contains at least one terpenoid group and / or R1, R2, R3 and / or R1', R2', R3' of the antimicrobial group defined above are terpenoid moieties, the core of the particle of the present invention is a polyhedral oligomeric silsesquioxane (POSS).

[0162] In some embodiments, the antimicrobial groups of formulae (1)-(6) are selected from: (a) tertiary amines (no R3 and / or R3') or tertiary ammoniums (R3 and / or R3' are H) where the nitrogen atom of each tertiary amine / ammonium has at least one bond to X1 or X2 and one bond to a terpenoid moiety; (b) tertiary amines (no R3 and / or R3') or tertiary ammoniums (R3 and / or R3' are H) where the nitrogen atom of each tertiary amine / ammonium has one bond to X1 or X2 and two bonds to a terpenoid moiety, which may be the same as or different from each other, or a salt of said tertiary amines; (c) quaternary ammonium groups where the nitrogen atom of each quaternary ammonium group has at least one bond to X1 or X2 and one or two bonds to a terpenoid moiety, which may be the same as or different from each other. Each possibility represents a separate embodiment of the present invention.

[0163] In one embodiment, the antimicrobial group [- + N(R4)(R5)(R6), - + N(R4')(R5')(R6'), [ka] R6, R8 to R defined in structures (I) and (IE) 11 , R6' and / or R8' to R 11 ' is the terpenoid moiety.

[0164] In another embodiment, the antimicrobial group of the present invention contains at least one terpenoid group and / or R, R to R of the antimicrobial group defined above. 11 , R6' and / or R8' to R 11 When ' is a terpenoid moiety, the core of the particles of the invention is a polyhedral oligomeric silsesquioxane (POSS).

[0165] The term "terpenoid," also known as "isoprenoid," refers to a large class of naturally occurring compounds derived from a five-carbon isoprene unit. The "terpenoid moiety" is derived from terpenoid.

[0166] In some embodiments, the terpenoid moiety may be, for example, a "terpenoidyl" bonded directly to a group (e.g., cinnamyl: [ka] ); or, for example, a "terpenoidylene" directly bonded to two groups (e.g., cinnamylene, e.g., [ka] ). In one embodiment, the terpenoid moiety is directly bonded to three or more groups. In one embodiment, the terpenoid moiety is a cinnamyl or cinnamylene group derived from cinnamaldehyde, cinnamic acid, curcumin, biscydone, or cinnamyl alcohol. In another embodiment, the terpenoid moiety is a bornyl or bornylene group derived from camphor, a bornyl halide, or bornyl alcohol. In another embodiment, the terpenoid moiety is derived from citral. In another embodiment, the terpenoid moiety is derived from perillaldehyde. Each possibility represents a separate embodiment of the present invention.

[0167] Cinnamaldehyde is a natural aldehyde extracted from the Cinnamomum genus. It is known for its low toxicity, as well as its effectiveness against a variety of bacteria and fungi.

[0168] Camphor is found in the wood of the camphor tree (Cinnamomum camphora) and even the Kapur tree. It also occurs in several other related trees of the Lauraceae family, such as Ocotea usambarensis, as well as other natural sources. Camphor can be produced synthetically from turpentine. Camphor can be found as the R or S enantiomer, mixtures of enantiomers, and racemic mixtures. Each possibility represents a separate embodiment of the present invention.

[0169] Citral, or 3,7-dimethyl-2,6-octadienal or lemonal, is a mixture of two diastereomeric terpenoids. The two compounds are double bond isomers. The E isomer is known as geranial or citral A. The Z isomer is known as neral or citral B. Citral is known to have antibacterial activity.

[0170] Perillaldehyde, also known as perillaaldehyde, is a naturally occurring terpenoid found most abundantly in the annual herb Perilla frutescens as well as a wide variety of other plants and essential oils.

[0171] Other examples of terpenoids include, but are not limited to, curcuminoids found in turmeric and mustard seeds, citronellal found in Cymbopogon (lemongrass), and carvacrol found in Origanum vulgare (oregano), thyme, peppercorns, wild bergamot, and Mexican oregano (Lippia graveolens). Each possibility represents a separate embodiment of the present invention.

[0172] According to the above embodiment, the antimicrobially active terpenoid moiety is selected from the group consisting of: [ka] or any combination thereof; [ka] Each possibility represents a separate embodiment of the present invention.

[0173] Non-limiting examples of antimicrobially active quaternary ammonium groups according to the principles of the present invention include: [ka] TIFF2025505704000079.tif234142TIFF2025505704000080.tif214143TIFF2025505704000081.tif217132TIFF2025505704000082.tif40132, R 2 is alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl, or any combination thereof; R 3 is an alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, an alkenyl, an alkynyl, or any combination thereof; R4 and R5 are independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof; R is alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof.

[0174] Non-limiting examples of functional antimicrobially active tertiary amine groups or their protonated forms according to the principles of the present invention are: [ka] TIFF2025505704000084.tif217141TIFF2025505704000085.tif224143TIFF2025505704000086.tif41133, where R 2 is alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof.

[0175] Inorganic Core In one embodiment, the inorganic core of the particles of the present invention comprises silica, a metal, a metal oxide, or a zeolite, with each possibility representing a separate embodiment of the present invention.

[0176] In one embodiment, the core of the particles of the present invention comprises silica (SiO2). The silica may be in any form known in the art, non-limiting examples of which include polyhedral oligomeric silsesquioxanes (POSS), amorphous silica, dense silica, aerogel silica, porous silica, mesoporous silica, and fumed silica. Each possibility represents a separate embodiment of the present invention.

[0177] The surface density of active groups on the particle surface can proportionally affect its antimicrobial activity. In another embodiment, the core of the particles of the present invention is made of silicate (SiO4 -4 ) glasses or ceramics. Non-limiting examples of silicates include aluminosilicates, borosilicates, barium silicate, barium borosilicate, and strontium borosilicate. Each possibility represents a separate embodiment of the present invention.

[0178] In another embodiment, the core of the particles of the present invention comprises a surface activating metal selected from the group of silver, gold, platinum, palladium, copper, zinc, and iron, with each possibility representing a separate embodiment of the present invention.

[0179] In another embodiment, the core of the particles of the present invention comprises a metal oxide selected from the group of zirconium dioxide, titanium dioxide, vanadium dioxide, zinc oxide, copper oxide, and magnetite, with each possibility representing a separate embodiment of the present invention.

[0180] In one embodiment, the inorganic core is a polyhedral oligomeric silsesquioxane (POSS) core.

[0181] In some embodiments, provided herein are antimicrobial particles comprising a POSS core, wherein each silicon atom of the POSS is functionalized with at least one antimicrobial group or at least one functional polymerizable group, and the molar ratio of silicon atoms functionalized with at least one antimicrobial group to silicon atoms functionalized with at least one functional polymerizable group is 10:1 to 1:10, respectively. In another embodiment, the ratio is 9:1 to 1:9. In another embodiment, the ratio is 8:1 to 1:8. In another embodiment, the ratio is 7:1 to 1:7. In another embodiment, the ratio is 6:1 to 1:6. In another embodiment, the ratio is 5:1 to 1:5. In another embodiment, the ratio is 4:1 to 1:4. In another embodiment, the ratio is 3:1 to 1:3. In another embodiment, the ratio is 2:1 to 1:2. Each possibility represents a separate embodiment of the present invention. In one embodiment, the antimicrobial group is a quaternary ammonium. In one embodiment, the antimicrobial group is a tertiary amine. In one embodiment, the antimicrobial group is a tertiary ammonium. In one embodiment, the antimicrobial group is of the following formula: + N(R1)(R2)(R3), - + N(R1)(R2)-,- + NH(R1)(R2), - + NH(R1)-, -N(R1)(R2), -N(R1)-, - + N(R1')(R2')(R3'), - + N(R1')(R2')-, - + NH(R1')(R2'), - +In one embodiment, the antimicrobial group comprises a quaternary ammonium and / or pyridinium, represented by the formula: [ka] TIFF2025505704000088.tif41132In formula, R4~R 11 and R4'~R 11 ' is as described above. In alternative embodiments, the antimicrobial group may be selected from: (a) a quaternary ammonium group comprising at least one terpenoid moiety or one hydrophobic group; and (b) a pyridinium group. Each possibility represents a separate embodiment of the present invention.

[0182] In one embodiment, the functional polymerizable groups include acrylate, epoxy, vinyl and / or isocyanate groups.

[0183] In some embodiments, antimicrobial particles are provided that include a polyhedral oligomeric silsesquioxane (POSS) core, where each silicon atom of the POSS is functionalized with at least one quaternary ammonium group or at least one functional polymerizable group, where the functional polymerizable group comprises an acrylate, epoxy, isocyanate, or vinyl group, where the number of quaternary ammonium groups per silicon atom is 1-200, and the molar ratio of silicon atoms functionalized with at least one quaternary ammonium to silicon atoms functionalized with at least one functional polymerizable group is 10:1-1:10, respectively. In another embodiment, the ratio is 9:1-1:9. In another embodiment, the ratio is 8:1-1:8. In another embodiment, the ratio is 7:1-1:7. In another embodiment, the ratio is 6:1-1:6. In another embodiment, the ratio is 5:1-1:5. In another embodiment, the ratio is 4:1-1:4. In another embodiment, the ratio is 3:1-1:3. In another embodiment, the ratio is from 2: 1 to 1: 2. Each possibility, as well as subranges therein, represents a separate embodiment of the present invention.

[0184] In some embodiments, antimicrobial particles are provided that include a polyhedral oligomeric silsesquioxane (POSS) core, where each silicon atom of the POSS is functionalized with at least one quaternary ammonium group or at least one functional polymerizable group comprising an acrylate, epoxy, isocyanate, or vinyl group, where the functional polymerizable group has a number of quaternary ammonium groups per silicon atom between 2 and 200, and the molar ratio of silicon atoms functionalized with at least one quaternary ammonium to silicon atoms functionalized with at least one functional polymerizable group is between 10:1 and 1:10, respectively. In another embodiment, the ratio is between 9:1 and 1:9. In another embodiment, the ratio is between 8:1 and 1:8. In another embodiment, the ratio is between 7:1 and 1:7. In another embodiment, the ratio is between 6:1 and 1:6. In another embodiment, the ratio is between 5:1 and 1:5. In another embodiment, the ratio is between 4:1 and 1:4. In another embodiment, the ratio is between 3:1 and 1:3. In another embodiment, the ratio is from 2: 1 to 1: 2. Each possibility, as well as subranges therein, represents a separate embodiment of the present invention.

[0185] In some embodiments, the silicon atom of the POSS (the core of the antimicrobial particle) is functionalized with at least one quaternary ammonium group. "Silicon atom of the POSS functionalized with at least one quaternary ammonium group" refers to a silicon atom of the POSS (core) linked to one or more quaternary ammonium groups by a linker. In other embodiments, the silicon atom is linked to the ammonium group via an alkylene group. Non-limiting examples include Si-alkylene-[N + (R1)(R2)-alkylene] n -N + (R1)(R2)(R3), where n is 1 to 200, and R1, R2, and R3 are described above. In another embodiment, n is 2 to 200. In another embodiment, n is 1, 2, 3, 4, 5, or 6. In another embodiment, n is 1 to 10, 2 to 10, 2 to 50, or 2 to 5.

[0186] In some embodiments, provided herein are antimicrobial particles comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized with an N-alkylated 3-(2-aminoethylamino)propyl, a propyl end group is bonded to the silicon atom, or functionalized with at least one functional polymerizable group selected from acrylate, epoxy, isocyanate, and vinyl groups, the number of quaternary ammonium groups per silicon atom is 2-200, and the molar ratio of silicon atoms functionalized with the N-alkylated 3-(2-aminoethylamino)propyl to silicon atoms functionalized with at least one functional polymerizable group is 10:1-1:10, respectively. In another embodiment, the ratio is 9:1-1:9. In another embodiment, the ratio is 8:1-1:8. In another embodiment, the ratio is 7:1-1:7. In another embodiment, the ratio is 6:1-1:6. In another embodiment, the ratio is 5:1-1:5. In another embodiment, the ratio is from 4:1 to 1:4. In another embodiment, the ratio is from 3:1 to 1:3. In another embodiment, the ratio is from 2:1 to 1:2. Each of these possibilities, as well as subranges therein, represents a separate embodiment of the present invention.

[0187] In some embodiments, the silicon atom of the POSS (the core of the antimicrobial particle) is functionalized with at least one functional polymerizable group, and the functional polymerizable group comprises an acrylate, an epoxy, an isocyanate, or a vinyl group. In one embodiment, "a silicon atom of the POSS (the core of the antimicrobial particle) functionalized with at least one functional polymerizable group" refers to a silicon atom of the POSS (core) that is linked to an acrylate, an epoxy, an isocyanate, or a vinyl group by a linker. In other embodiments, the Si is linked to an acrylate, an epoxy, or a vinyl through an alkylene group. Non-limiting examples of such silicon atom functionalization include Si-alkylene-OC(O)-CH=CH2 (Si-acrylate); [ka] (Si-epoxy); Si-alkylene-CH=CH2 (Si-vinyl) or Si-alkylene-N=C=O (Si-isocyanate). In some embodiments, the "Si" in the "(acrylate)"; "(epoxy)"; "(vinyl)"; or "(isocyanate)" structure is an integral part of an inorganic core, and the Si atom is covalently bonded / connected to three oxygen atoms of the core (in addition to the covalent bond / connection to the "alkylene"). Each possibility represents a separate embodiment of the present invention.

[0188] In some embodiments, when the core is inorganic, the polymerizable units are Si-alkylene-OC(O)-CH=CH2 (Si-acrylate); [ka] (Si-epoxy); Si-alkylene-CH=CH2 (Si-vinyl) or Si-alkylene-N=C=O (Si-isocyanate), where "Si" is part of a siloxane moiety directly bonded to the core.

[0189] In some embodiments, provided herein are antimicrobial particles comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized with at least one quaternary ammonium group, or propyl acrylate, wherein a propyl end group is linked to the silicon atom, the number of quaternary ammonium groups per silicon atom is 2-200, and the molar ratio of silicon atoms functionalized with at least one quaternary ammonium to silicon atoms functionalized with propyl acrylate is 10:1-1:10, respectively. In another embodiment, the ratio is 9:1-1:9. In another embodiment, the ratio is 8:1-1:8. In another embodiment, the ratio is 7:1-1:7. In another embodiment, the ratio is 6:1-1:6. In another embodiment, the ratio is 5:1-1:5. In another embodiment, the ratio is 4:1-1:4. In another embodiment, the ratio is 3:1-1:3. In another embodiment, the ratio is 2:1-1:2. Each possibility, as well as subranges thereof, represents a separate embodiment of the present invention.

[0190] In some embodiments, provided herein are antimicrobial particles comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized with N-alkylated 3-(2-aminoethylamino)propyl, with a propyl end group bonded to the silicon atom, or functionalized with propyl acrylate, with a propyl end group bonded to the silicon atom, the number of quaternary ammonium groups per silicon atom being 2-200, and the molar ratio of silicon atoms functionalized with N-alkylated 3-(2-aminoethylamino)propyl to silicon atoms functionalized with propyl acrylate is 10:1-1:10, respectively. In another embodiment, the ratio is 9:1-1:9. In another embodiment, the ratio is 8:1-1:8. In another embodiment, the ratio is 7:1-1:7. In another embodiment, the ratio is 6:1-1:6. In another embodiment, the ratio is 5:1-1:5. In another embodiment, the ratio is 4:1-1:4. In another embodiment, the ratio is from 3:1 to 1:3. In another embodiment, the ratio is from 2:1 to 1:2. Each of these possibilities, as well as subranges therein, represents a separate embodiment of the present invention.

[0191] In some embodiments, the antimicrobial particles provided herein comprise an inorganic or organic core, and the molar ratio of the antimicrobially active units to the polymerizable units is between 10:1 and 1:10, respectively. In other embodiments, the ratio is between 4:1 and 1:1, respectively. In various embodiments, the ratio is 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1, respectively, or any range or subrange thereof. In other embodiments, the antimicrobial units comprise antimicrobial groups comprising a tertiary amine or tertiary ammonium; or a quaternary ammonium and / or pyridinium, represented by the following formula: - + N(R1)(R2)(R3), - + N(R1)(R2)-,- + NH(R1)(R2), - + NH(R1)-, -N(R1)(R2), -N(R1)-, -+ N(R1')(R2')(R3'), - + N(R1')(R2')-, - + NH(R1')(R2'), - + NH(R1')-, -N(R1')(R2'), -N(R1')-, [ka] During the ceremony, R1~R 11 and R1'~R 11 ' is as above.

[0192] In another embodiment, the activity of the quaternary ammonium, tertiary amine or tertiary ammonium or pyridinium remains strong at any pH.

[0193] In some embodiments, the antimicrobial particles provided herein comprise a POSS core, wherein the molar ratio of silicon atoms (in the POSS) functionalized with at least one antimicrobial group to silicon atoms (in the POSS) functionalized with at least one functional polymerizable group is 10:1 to 1:10, respectively. In other embodiments, the ratio is 4:1 to 1:1, respectively. In various embodiments, the ratio is 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, or 10:1, respectively, or any range or subrange thereof. In other embodiments, the antimicrobial group comprises a tertiary amine or tertiary ammonium; or a quaternary ammonium and / or pyridinium, represented by the following formula: - + N(R1)(R2)(R3), - + N(R1)(R2)-,- + NH(R1)(R2), - + NH(R1)-, -N(R1)(R2), -N(R1)-, - + N(R1')(R2')(R3'), - + N(R1')(R2')-, - + NH(R1')(R2'), - +NH(R1')-, -N(R1')(R2'), -N(R1')-, [ka] During the ceremony, R1~R 11 and R1'~R 11 ' is as above.

[0194] In another embodiment, the activity of the quaternary ammonium, tertiary amine or tertiary ammonium or pyridinium remains strong at any pH.

[0195] In some embodiments, provided herein are antimicrobial particles comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized with at least one antimicrobial group or at least one functional polymerizable group, the functional polymerizable group comprising an acrylate, epoxy, isocyanate, or vinyl group, and the molar ratio of silicon atoms functionalized with at least one quaternary ammonium to silicon atoms functionalized with at least one functional polymerizable group is 10:1 to 1:10, respectively. In another embodiment, the ratio is 9:1 to 1:9. In another embodiment, the ratio is 8:1 to 1:8. In another embodiment, the ratio is 7:1 to 1:7. In another embodiment, the ratio is 6:1 to 1:6. In another embodiment, the ratio is 5:1 to 1:5. In another embodiment, the ratio is 4:1 to 1:4. In another embodiment, the ratio is 3:1 to 1:3. In another embodiment, the ratio is 2:1 to 1:2. Each possibility, as well as subranges thereof, represents a separate embodiment of the present invention.

[0196] In some embodiments, the silicon atom of the POSS (core) is linked to one or more quaternary or pyridinium ammonium groups, tertiary ammonium or tertiary amine groups by a linker. In other embodiments, Si is linked to the ammonium / amine group via an alkylene group. Non-limiting examples of quaternary ammonium linked to the Si atom include Si-alkylene-[N +(R1)(R2)-alkylene] n -N + (R1)(R2)(R3), where n is 1-200, and R1, R2, and R3 are described above. In another embodiment, the quaternary ammonium linked to the silicon atom is N-alkylated 3-(2-aminoethylamino)propyl, with the propyl terminus linked to the silicon atom. In another embodiment, the N-alkylated group comprises C1-C18 alkyl units. In another embodiment, the N-alkylated group comprises C1-C18 alkyl units, with at least one alkyl unit being a C4-C8 alkyl.

[0197] In some embodiments, the surface area of ​​the POSS core is 2 The number of quaternary ammonium groups (=antibacterial) per sq nm (nm 2 ) of the POSS core surface. 2 The number of quaternary ammonium groups (=antibacterial) per sq nm (nm 2 0.01-15, 0.01-12, 0.01-10, 0.01-8, 0.01-5, 0.01-3, 0.001-2, 0.001-3, 0.001-5, 0.5-3 or 0.5-5 antimicrobial units per 1000 sq. m.), with each range representing a separate embodiment of the present invention. The surface density of active groups on the particle surface proportionally affects its antimicrobial activity.

[0198] In one embodiment, the core of the antimicrobial particles of the invention is a polyhedral oligomeric silsesquioxane (POSS) in which at least one silicon atom is capped. In another embodiment, "capped" silicon in a POSS means that said Si atom is not covalently connected / bonded to an antimicrobially active unit or a polymerizable unit, but is covalently connected / bonded, for example, to hydrogen or an organic moiety, such as alkyl, aryl, etc. In another embodiment, the ratio of capped Si atoms to uncapped Si atoms is 4:1 to 1:4. In another embodiment, the ratio is 3:1 to 1:3. In another embodiment, the ratio is 2:1 to 1:2. Each possibility represents a separate embodiment of the present invention.

[0199] For example, up to 70% of the Si atoms may be capped, for example with methyl, butyl, benzyl and / or propyl groups, which may be substituted or unsubstituted. In various embodiments, 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, or any intermediate percentage of the Si atoms may be capped.

[0200] Organic Core In some embodiments, the core of the antimicrobial particle is an organic core. In one embodiment, the organic core comprises at least one aliphatic polymer. "Aliphatic polymer" as used within the scope of the present invention refers to a polymer made of aliphatic monomers that may be substituted with various side groups, including (but not limited to) aromatic side groups. Aliphatic polymers that may be included in the particles according to the present invention include nitrogen atoms (and other heteroatoms) as part of the polymer backbone. In one embodiment, the core of the particle comprises an organic polymer core that includes an amine that may be substituted with R1, R2 / or R3 as defined for Structure 1, or an imine that is chemically modified to an amine and then substituted with R1, R2 / or R3 as defined for Structure 1. In one embodiment, the core of the particle is an organic polymer core, and includes as the antimicrobial group R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28, R29, R30, R310, R320, R3310, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R44, R45, R46, R47, R48, R49, R50, R51, R52, R53, R54, R55, R56, R57, R58, R59, R61, R62, R63, R64, R65, R66, R67, R68, R69, R61, R62, R64, R65, R66, R67, R68, R69, R69, R7 4’ , R 5’ and / or R 6’or chemically modified to an amine, which may then be substituted with R4, R5, R6, R 4’ , R 5’ and / or R 6’ In other embodiments, the antimicrobial group comprises a tertiary amine or tertiary ammonium; or a quaternary ammonium and / or pyridinium, as represented by the formula: - + N(R1)(R2)(R3), - + N(R1)(R2)-,- + NH(R1)(R2), - + NH(R1)-, -N(R1)(R2), -N(R1)-, - + N(R1')(R2')(R3'), - + N(R1')(R2')-, - + NH(R1')(R2'), - + NH(R1')-, -N(R1')(R2'), -N(R1')-, [ka] During the ceremony, R1~R 11 and R1'~R 11 ' is as above.

[0201] In another embodiment, the activity of the quaternary ammonium, tertiary amine or tertiary ammonium or pyridinium may remain strong at any pH.

[0202] In one embodiment, the functional polymerizable group comprises an acrylate, epoxy, vinyl, or isocyanate group.

[0203] In some embodiments, when the core is organic, the polymerizable units are {N}-alkylene-OC(O)-CH=CH2 (N-acrylate); [ka] (N-epoxy);{N}-alkylene-CH=CH2 (N-vinyl) or {N}-alkylene-N=C=O (N-isocyanate), where "Si" is part of a siloxane moiety directly attached to the core and "{N}" is a nitrogen (containing a nitrogen atom) linker, such as amide, amine, guanidine, imidazole, etc.

[0204] Non-limiting examples of aliphatic polymers are polystyrene (PS), polyvinyl chloride (PVC), polyethyleneimine (PEI), polyvinylamine (PVA), poly(allylamine) (PAA), poly(aminoethyl acrylate), polypeptides with pending alkylamino groups, chitosan, and copolymers (combinations) thereof. Each possibility represents a separate embodiment of the invention. In one embodiment, the polymer is polyethyleneimine (PEI).

[0205] In another embodiment, the organic core comprises at least one aromatic polymer selected from the following group: polystyrene, aminomethylated styrene polymer, aromatic polyester, polyethylene terephthalate, and polyvinylpyridine. For example, the at least one aromatic polymer may comprise polyethylene terephthalate.

[0206] In another embodiment, the polymer core may be linked to the antimicrobially active unit directly (e.g., in structures (1)-(3): L3 is a bond) or via a linker. In another embodiment, the polymer core may be linked to the antimicrobially active unit directly (e.g., in structures (I), (IE), and (II)-(VII): L6 is a bond) or via a linker. Each possibility represents a separate embodiment of the present invention.

[0207] In alternative embodiments, the polymer core may be linked to the polymerizable units directly (e.g., in structure (7): L8 is a bond) or via a linker. Each possibility represents a separate embodiment of the present invention.

[0208] In one embodiment, the organic polymer core comprises a combination of two or more different organic polymers, hi another embodiment, the organic polymer core comprises a copolymer.

[0209] Resin / composite containing particles of the present invention In some embodiments, the antimicrobial particles of the present invention may be mixed with a polymer matrix to form a resin / composite. In some embodiments, the functional polymerizable groups in the particles interact with the matrix to prevent leaching of the particles from the resin / composite. In one embodiment, polymerization of the functional polymerizable groups (e.g., in vivo) further prevents or reduces leaching.

[0210] In some embodiments, the ratio between the antimicrobial active unit and the polymerizable unit may be in the range of 10:1 to 1:10, or more particularly in the range of 4:1 to 1:1. Surprisingly, at such ratios, the leakage of the particles from the composite is reduced by 1%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or intermediate values, compared to antimicrobial particles that do not contain polymerizable units. In some embodiments, the ratio of silicon atoms of the POSS (core) linked to antimicrobial groups (e.g., quaternary ammonium, tertiary amine, tertiary ammonium) to silicon atoms of the POSS (core) linked to functional polymerizable groups (e.g., acrylate, epoxy, vinyl, isocyanate) may be in the range of 10:1 to 1:10, or more particularly in the range of 4:1 to 1:1. Surprisingly, such ratios reduced particle leakage from the composite by 1%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or intermediate values ​​compared to antimicrobial particles not containing functional polymerizable groups.

[0211] The particles of the present invention demonstrate enhanced antimicrobial activity. Without being bound by any theory or mechanism, it can be hypothesized that such activity is due to the presence of dense antimicrobial groups on the surface of a given core, as well as a high density of particles packed on the surface of the host material. This density increases as the number of antimicrobial groups contained by each antimicrobial active unit in the particles of the present invention increases, resulting in a high local concentration of active functional polymerizable groups, which results in a high effective concentration of antimicrobial groups, making it possible to achieve effective bacteria / microorganism annihilation with the use of a relatively small number of particles. The denseness of the antimicrobial groups is due, among other things, to a large number of antimicrobial active units protruding from each particle surface. Thus, the antimicrobial groups cover a large portion of the available surface area of ​​the particle (the width dimension covering the surface). The surface density of the antimicrobial groups results in a high effective concentration that promotes the antimicrobial inhibitory effect. In accordance with the principles of the present invention, a high surface density dictates a high antimicrobial efficiency.

[0212] The antimicrobial group of the present invention can be in the form of a tertiary amine, or in the form of a protonated tertiary amine, or in the form of a quaternary ammonium salt, or in the form of a pyridinium salt, as described above. The ammonium / pyridinium group is positively charged, so its charge is balanced by an anion. In certain embodiments, in the particles according to the present invention, this anion is a halide, such as fluoride, chloride, bromide or iodide. For example, the anion can be fluoride. Other possible anions include, but are not limited to, bicarbonate, nitrate, phosphate, acetate, fumarate, succinate and sulfate. Each possibility represents a separate embodiment of the present invention.

[0213] The core of such particles may generally be of a morphology selected from spherical, amorphous polygonal, shallow flake, and rod. In some embodiments, the core is spherical and has a diameter of about 5 to about 100,000 nm. In some embodiments, the core is spherical and has a diameter of about 1000 to 100,000 nm. In some embodiments, the core is spherical and has a diameter of about 100 to 1000 nm. In some other embodiments, the particle is of a size of about 20 to about 200 nm. In some other embodiments, the core is of a size of about 20 to about 200 nm. In some other embodiments, the diameter of the core may be of a size of about 20 to about 200 nm. In another embodiment, the diameter of the core may be of a size of about 20 to about 200 nm. In one embodiment, the core is POSS and of a morphology selected from spherical, amorphous polygonal, shallow flake, and rod. In some exemplary embodiments, the POSS core is spherical and has a diameter of about 5 to about 100,000 nm. In some exemplary embodiments, the POSS core is spherical and has a diameter of about 1000 to 100,000 nm. In some exemplary embodiments, the POSS core is spherical and has a diameter of about 100 to 1000 nm. In some other embodiments, the particles are about 20 to about 200 nm in size. In some other embodiments, the core is about 20 to about 200 nm in size. In some other embodiments, the inorganic core is POSS and the particles are about 20 to about 200 nm in size. In another embodiment, the inorganic core is POSS and the core diameter is about 20 to about 200 nm in size. Each possibility represents a separate embodiment of the present invention.

[0214] Certain Compositions Comprising the Particles of the Invention Some embodiments include compositions comprising one or more types of the disclosed antimicrobial particles and a polymeric material / resin as a matrix. For example, the particles can be uniformly dispersed in the polymeric material (matrix). In some embodiments, the polymeric material can include organic polymers, inorganic polymers, or any combination thereof. The organic polymers can include hydrogels, polyolefins, epoxy resins, acrylate resins, or any combination thereof. The inorganic polymers can include silicone polymers, ceramics, metals, or any combination thereof.

[0215] In various embodiments, the weight ratio of particles to polymeric material can be 0.25-5 wt%, 0.25-1 wt%, 1-2 wt%, 2-3 wt%, 3-4 wt%, 4-5 wt%, or any other subrange.

[0216] In some embodiments, the compositions provided herein are capable of filling dental caries cavities and are dental restorative endodontic filling materials for filling root canal spaces in root canal treatments or are selected from the group consisting of dental restorative materials intended for temporary and definitive tooth restoration or tooth replacement, dental inlays, dental onlays, crowns, partial dentures, complete dentures, dental implants, dental implant abutments, and cements intended for permanently bonding crowns, bridges, onlays, partial dentures and orthodontic appliances onto tooth enamel and dentin.

[0217] In some embodiments, the compositions provided herein further comprise a filler. In other embodiments, the composition comprises 60-95% w / w of the filler and 10-30% w / w of the resin / polymeric material / matrix. In other embodiments, the composition comprises 78.5% w / w of the filler. In other embodiments, the composition comprises 20% w / w of the resin / polymeric material / matrix. In other embodiments, the composition comprises 78.5% w / w of the filler and 20% w / w of the resin / polymeric material / matrix.

[0218] In some embodiments, the resin is prepared by mixing bisphenol A glycidyl ether dimethacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA) and urethane dimethacrylate (UDMA) to obtain a clear blend, followed by mixing in camphoquinone (CQ), benzoin methyl ether (BME), ethyl 4-(dimethylamino)benzoate (EDB) and butylated hydroxytoluene (BHT) to obtain the resin.

[0219] In some embodiments, the compositions provided herein comprise: -CQ 0.05~0.5%w / w; -BME 0.05~0.5%w / w; -EDB 0.05~0.5%w / w; -BHT 0.005~0.05%w / w; -BisGMA 3-10% w / w; -TEGDMA 3~10%w / w; -UDMA 3~10%w / w; - inorganic glass filler 60-95% w / w; and -Antibacterial particles 0.25-5% w / w.

[0220] In some other embodiments, the compositions provided herein comprise: -CQ 0.1%w / w; - BME 0.1% w / w; -EDB 0.1%w / w; - BHT 0.01% w / w; -BisGMA 6.56%w / w; -TEGDMA 6.56%w / w; -UDMA 6.56%w / w; - inorganic glass filler 78.5% w / w; and -Antibacterial particles 1.5% w / w.

[0221] In some embodiments, the compositions of the invention comprise the antimicrobial particles of the invention and a polymeric material comprising an organic polymer, an inorganic polymer, or any combination thereof. In some embodiments, the particles described herein are dispersed in the polymeric material. In another embodiment, the particles are uniformly dispersed within the polymeric material. In another embodiment, the particles are found on the surface of the polymeric material. In another embodiment, the particles covalently interact with the polymeric material. In another embodiment, the antimicrobial particles are mechanically embedded within the polymeric material. In another embodiment, the particles are three-dimensionally "locked" between the polymer chains, preventing them from migrating out of the composite network. The strong hydrophobic nature of these particles also serves to prevent the particles from migrating into hydrophilic surroundings, such as in physiological, dental, orthopedic, or other medical applications. In one embodiment, the particles comprise functional polymerizable groups capable of reacting with portions of the polymeric material. In another embodiment, the particles chemically interact with the polymeric material. In another embodiment, the particles comprise functional polymerizable groups that react with monomers to provide the polymeric material of the composition. In other embodiments, the particles comprise functional polymerizable groups that react with monomers to provide polymers in addition to (and / or with) the polymeric material of the composition. In another embodiment, the reaction of the functional polymerizable group with the polymeric material and / or monomer can be catalyzed and / or initiated by a catalyst and / or (photo)initiator. In another embodiment, non-limiting examples of photoinitiators include camphorquinone (CQ), benzoin methyl ether (BME) and ethyl 4-(dimethylamino)benzoate (EDB). In another embodiment, the particles are a mixture of various particles.

[0222] In some embodiments, the compositions of the present invention comprise the antimicrobial particles of the present invention and a polymeric material comprising an organic polymer, an inorganic polymer, or any combination thereof. In another embodiment, the polymeric material comprises a thermoplastic polymer, a thermosetting polymer, or any combination thereof. In another embodiment, the organic polymer comprises a hydrogel, a polyolefin, such as polyvinyl chloride (PVC), polyethylene, polystyrene, and polypropylene, an epoxy resin, an acrylate resin, such as polymethylmethacrylate, a polyurethane, or any combination thereof. In another embodiment, the inorganic polymer comprises a silicone polymer, such as polydimethylsiloxane (PDMS), a ceramic, a metal, or any combination thereof. In another embodiment, the hydrogel is a poloxamer or an alginate. In another embodiment, a commercially available poloxamer is used or is formed by reaction of the polymer with other reagents. In another embodiment, the polymer is a poly(ethylene glycol) (PEG) with reactive end groups (e.g., the epoxide in PEG-diglycidyl ether) and the reagent has multiple reactive sites (e.g., diethylenetriamine). Each possibility represents a separate embodiment of the present invention.

[0223] In some embodiments, the weight ratio of the particles to the polymeric material is between 0.25 and 5%. In other embodiments, the weight ratio is between 0.5 and 2%. In other embodiments, the weight ratio is between 1 and 5%.

[0224] Another polymeric material used in the context of the present invention is a resin used in dental, surgical, chirurgical and orthopedic composites. In such applications, the antimicrobial particles can be initially dispersed within the resin part or added simultaneously with the filler or any other solid components (if any). Most of these resins are acrylic or epoxy type monomers that are polymerized in vivo. In some embodiments, the antimicrobial particles are also polymerized in vivo (regardless of the identity or presence of additional polymeric materials of the matrix).

[0225] Process for preparing antibacterial particles Preparation of antibacterial particles containing one monomer unit per one antibacterial activity unit The particles of the present invention can be prepared according to various methods, depending on the nature of the core, the antimicrobially active group, and the presence or absence of a linker. Some non-limiting examples of preparation methods are provided below.

[0226] In one embodiment, the present invention provides a method for preparing antimicrobial particles, wherein the particles comprise at least one antimicrobially active unit and at least one polymerizable unit, with one monomeric unit found per antimicrobially active unit. In a further embodiment, the ratio of the number of antimicrobial units to polymerizable units in the particles prepared by said process is 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1 or 10:1, respectively, or any range or subrange thereof. Such processes are described in detail below.

[0227] A representative method for preparing particles of the invention, in which the antimicrobially active group is a tertiary amine or quaternary ammonium group containing at least one terpenoid moiety, is shown in FIG. 4 for standard particles. According to FIG. 4, the core as defined herein is functionalized with a primary amine, which may already contain (at least one) polymerizable unit covalently connected / bound thereto (directly or indirectly via a linker as described herein). The primary amine is reacted with an aldehyde to first obtain an imine (Schiff base) intermediate of formula (A'), which is then reacted with a second aldehyde under reductive amination conditions to obtain a tertiary amine of formula (B'). RC(=O)H and R'C(=O)H represent an aldehyde that is a terpenoid or is derived from a terpenoid, respectively. RC(=O)H and R'C(=O)H may be the same or different from each other. The conversion of the tertiary amine to a quaternary ammonium group is optional, and the tertiary amine and R 1 is a C1-C4 alkyl group and Y is a leaving group such as a halogen or a sulfonate;1 -Y. In one embodiment, the core already comprises (at least one) polymerizable unit covalently connected / bonded thereto (directly or indirectly via a linker as described herein). In another embodiment, the particle obtained from the above process shown in Figure 4 (B' or C') is further reacted to obtain an antimicrobial particle of the invention comprising at least one antimicrobially active unit and at least one polymerizable unit.

[0228] base [ka] It is understood that may represent any one or more of the following: 1. An organic core which is directly bonded to NH2 and which may be directly bonded to the polymerizable unit or indirectly bonded thereto via a linker as described herein.

[0229] 2. An organic core that is directly attached to the NH2 via a linker as described herein, and which may be directly attached to the polymerizable unit or indirectly attached thereto via a linker as described herein.

[0230] 3. An inorganic core which is directly bonded to NH2 and which may be directly bonded to the polymerizable unit or indirectly bonded thereto via a linker as described herein.

[0231] 4. An inorganic core that is directly bonded to the NH2 via a linker as described herein and that may be directly bonded to the polymerizable unit or indirectly bonded thereto via a linker as described herein.

[0232] The illustrated reaction (Figure 4) can be a "one-pot synthesis" or can involve two successive reactions with isolation of the intermediate formed in the first step. The first step is the formation of intermediate (A'), an imine (Schiff base), by reacting an amine-functionalized core with a terpenoid moiety in the presence of a reducing agent, in this case cinnamyl in the presence of NaBH4. If desired, the imine-functionalized core can be isolated at this stage. Alternatively, intermediate (A') can be further reacted with a terpenoid moiety in the presence of a reducing agent to give a tertiary amine (B') containing two terpenoid moieties. To obtain a quaternary ammonium, an additional alkylation step is performed as described in Figure 4.

[0233] Particles with enhanced thermal stability can be prepared in a manner similar to that described above and exemplified in FIG. 4 for standard particles, with some notable differences: in standard particles, R and R′ are terpenoid moieties, and in particles with enhanced thermal stability, R and R′ are each independently methyl, CF3, perhaloalkyl, aryl, -C(═O)OR, -C(═O)OC(═O)R, -C(═S)OR, -C(═O)SR, -C(═O)-R, -C(═S)-R, 1-alkenyl, or 1-alkynyl, R is alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof, and R is an alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof. 1 is methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 R is an alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof, and R is an alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof. In this case of the particles having improved thermal stability, R 1The final reaction involving -Y is required to arrive at ammonium, and is not optional. In one embodiment, the core already comprises (at least one) polymerizable unit covalently connected / bonded thereto (directly or indirectly via a linker as described herein), as described above with respect to the process of Figure 4. In another embodiment, the particle resulting from the above process shown in Figure 4(C') is further reacted to obtain an antimicrobial particle of the invention comprising at least one antimicrobially active unit and at least one polymerizable unit.

[0234] The process shown in FIG. 5 for the preparation of standard particles uses cinnamaldehyde, but is also applicable to other aldehydes. Thus, in some embodiments, the present invention provides particles comprising: (i) an inorganic or organic polymer core; (ii) an imine moiety, chemically bonded to the core, for example with a surface density of at least one imine group per 10 sq. nm, the imine group comprising a terpenoid moiety; and optionally, (iii) (at least one) polymerizable unit covalently connected / bonded to the core (directly or indirectly via a linker as described herein). The imine moiety is generally represented by the structure of formula (A') in FIG. 4. A more specific embodiment is the structure of formula (A) in FIG. 5. It will be understood by those skilled in the art that other imine intermediate compounds comprising other terpenoid groups as described herein are also encompassed by the present invention.

[0235] In one embodiment, the core of the process of Figure 5 already comprises (at least one) polymerizable unit covalently connected / bonded thereto (directly or indirectly via a linker as described herein). In another embodiment, the particle obtained from the above process shown in Figure 5 (B or C) is further reacted to obtain an antimicrobial particle of the invention comprising at least one antimicrobially active unit and at least one polymerizable unit.

[0236] Based on Figure 5 [ka] is understood to have any one of the meanings described above with respect to FIG.

[0237] A representative method for preparing standard particles in which the antimicrobially active group is a quaternary ammonium group containing one alkyl group having 4-18 carbon atoms is shown in Figures 6A-6C. The method includes three routes for preparing quaternary ammonium salt (QAS) functionalized particles: Figure 4A) using an initial reductive amination to achieve a tertiary amine, followed by an alkylation reaction; Figure 4B) a stepwise alkylation reaction; and Figure 4C) reacting a linker functionalized with a leaving group (e.g., Cl or other halogen) with the tertiary amine. R 1 and R 2 R represents C1-C4 alkyl, such as methyl, ethyl, propyl or isopropyl. 1 and R 2 may be different or the same group. Y represents any leaving group, such as Cl, Br, or I, or a sulfonate (e.g., mesyl, tosyl). In one embodiment, basis [ka] is understood to have any one of the meanings described above with respect to FIGS. 4A-4C and 5.

[0238] In one embodiment, the core of the process of Figures 6A-6C already comprises (at least one) polymerizable unit covalently connected / bonded thereto (either directly or indirectly via a linker as described herein). In another embodiment, the particles obtained from the above process shown in Figures 6A-6C are further reacted to obtain antimicrobial particles of the invention comprising at least one antimicrobial active unit and at least one polymerizable unit. In some other embodiments, the further reactions are detailed below in the sections entitled "Solid Support as a Method for Preparation of Antimicrobial Particles Comprising One Monomeric Unit per Antimicrobial Active Unit" and "Solution Method as a Method for Preparation of Antimicrobial Particles Comprising One Monomeric Unit per Antimicrobial Active Unit".

[0239] base [ka] It is understood that may represent any one or more of the following: 1. An organic core that is directly attached to Y, which may be directly attached to the polymerizable unit or indirectly attached thereto via a linker as described herein.

[0240] 2. An organic core that is directly attached to Y via a linker as described herein, and which may be directly attached to the polymerizable unit or indirectly attached thereto via a linker as described herein.

[0241] 3. An inorganic core which is directly bonded to Y and which may be directly bonded to the polymerizable unit or indirectly bonded thereto via a linker as described herein.

[0242] 4. An inorganic core which is directly bonded to Y via a linker as described herein and which may be directly bonded to the polymerizable unit or indirectly bonded thereto via a linker as described herein.

[0243] A similar method for preparing particles with improved thermal stability is shown in Figures 7A-7C. The method involves three routes for preparing quaternary ammonium salt (QAS) functionalized particles: Figure 7A) reaction involving R1-Y / R2-Y to achieve a tertiary amine, followed by a benzylation reaction; Figure 7B) a similar route to Figure 7A), performed in the reverse order; and Figure 7C) reaction of a linker functionalized with a leaving group (e.g., Cl or other halogen) with a tertiary amine. R4 and R5 are independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20Alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R-CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl or any combination thereof. Y represents any leaving group, such as Cl, Br or I, or a sulfonate (e.g., mesyl, tosyl). In one embodiment, the core already comprises (at least one) polymerizable unit covalently connected / bonded thereto (either directly or indirectly via a linker as described herein), as described above with respect to the process depicted in Figures 4-6. In another embodiment, the particles obtained from the above process depicted in Figures 7A-7C are further reacted to obtain antimicrobial particles of the invention comprising at least one antimicrobially active unit and at least one polymerizable unit.

[0244] In some other embodiments, further reactions are detailed below in the sections entitled "Solid Support Method for Preparing Antimicrobial Particles Comprising One Monomer Unit per Antimicrobial Activity Unit" and "Solution Method for Preparing Antimicrobial Particles Comprising One Monomer Unit per Antimicrobial Activity Unit."

[0245] Functionalization of the core can be carried out by solid support or solution methods.

[0246] Solid supports as a method for the preparation of antimicrobial particles containing one monomer unit per one unit of antimicrobial activity The preparation of functionalized standard particles is carried out in two general steps. First, a linker molecule is condensed onto the particle surface by hydrolysis of the leaving group (surface functionalization), resulting in an intermediate of formula (Figure 8, D'). Then, the functional sites of the linker molecule undergo further functionalization (linker functionalization) as mentioned in any of (Figures 4 to 7), resulting in functionalized particles of formula E' in Figure 8. The circles in Figure 8 represent organic or inorganic cores, and Q 1 , Q2 and Q 3 is independently selected from the group consisting of ethoxy, methoxy, methyl, ethyl, hydrogen, sulfonate and halide; Q 1 , Q 2 and Q 3 At least one of Q is a leaving group selected from ethoxy, methoxy, sulfonate (e.g., mesyl, tosyl) and halide, W is selected from the group consisting of NH2, halide, sulfonate and hydroxyl, and n is an integer from 1 to 16. For clarity, this scheme is 1 , Q 2 and Q 3 represents a leaving group, and Q 4 represents an antimicrobial group. A similar process is used to prepare functionalized particles with improved thermal stability, with the difference that W accommodates the same substituent, except that the NH2 moiety is replaced with an arylene-NH2 or benzylene-NH2 moiety. In one embodiment, polymerizable units are added in a similar manner to this solid support process of FIG. 8, in this case: [ka] W is a functional polymerizable group, and Q 1 ~Q 3 is as indicated herein above, and the addition of said polymerizable units (surface functionalization step) is carried out before or after the functionalization of the core with antimicrobial units (surface + linker functionalization). In another embodiment, when said polymerizable units are added to the particle, the second step of linker functionalization is not carried out, e.g., when the polymerizable units are introduced to the core / particle, only the step of "surface functionalization" is used.

[0247] Solution method for the preparation of antimicrobial particles containing one monomer unit per one unit of antimicrobial activity. In this method, a linker molecule is first functionalized with an antimicrobially active group to obtain an intermediate of formula (Figure 8, F'). In a second step, the intermediate (F') is precipitated onto the solid surface of the particle (surface functionalization) to obtain a functionalized particle of formula (Figure 8, E').

[0248] This process is illustrated in FIG. 9 for cinnamaldehyde standard particles, but is also applicable to other aldehydes.

[0249] A similar process is used to prepare functionalized particles with enhanced thermal stability, except that the NH2 moiety is replaced with an arylene-NH2 or benzylene-NH2 moiety, with the difference that W accommodates the same substituent. In one embodiment, polymerizable units are added in a similar manner to this solution-supported process of Figures 8-9, in this case: [ka] W is a functional polymerizable group, and Q 1 ~Q 3 is as indicated herein above, and the addition of said polymerizable units (surface functionalization step) is carried out before or after the functionalization of the core with antimicrobial units (surface + linker functionalization). In another embodiment, if said polymerizable units are added to the particle, the first step of linker functionalization is not carried out, e.g., if the polymerizable units are introduced to the core / particle, only the step of "surface functionalization" is used.

[0250] Preparation of antibacterial particles containing multiple monomer units per unit of antibacterial activity In one embodiment, the invention provides a method for preparing particles of the complex of the invention, the particles comprising a plurality of monomeric units per antimicrobial active unit. In a further embodiment, the particles prepared by the method have a ratio of the number of antimicrobial units to polymerizable units of 1:10, 1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1 or 10:1, respectively, or any range or subrange thereof. Such a process is described in detail below.

[0251] Solid supports as a method for preparing antimicrobial particles containing multiple monomer units per unit of antimicrobial activity The solid support method includes several steps. First, in the case of standard particles, linker molecules (a few percent of dilute solution) are condensed on the particle surface (surface functionalization) by (acid-catalyzed) hydrolysis of the leaving groups, and the linker is attached to the core (Figure 10, step 1). Next, the attached linker is extended. In another embodiment, this step is achieved synthetically through one or more steps. In another embodiment, the extension is achieved by successive additions of difunctionalized alkanes and diaminoalkanes, where the amines (of the attached linker and diaminoalkane) attack the electrophilic center of the difunctionalized alkane (Figure 10, steps 2 and 3). In another embodiment, such successive additions may be repeated 1 to 10 times. Finally, the antimicrobially active group (usually attached to an alkylene chain) is grafted to the resulting attached extended linker. In another embodiment, the grafting is achieved when the amines on the attached extended linker attack the acyl halide moiety of the molecule of the grafted antimicrobially active group (Figure 10, step 4). A similar process has been demonstrated for particles with improved thermal stability (Figure 11), where the ammonium end of the antibacterial active group was replaced with an anilinium end, R 1 ~R 3 R 4 ~R 6 In FIG. 10, R 1 and R 2 are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, conjugated alkyl, alkenyl, or any combination thereof; R 3 In FIG. 11, R4 and R5 are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20R6 is alkyl, 2,2,2-trisubstituted ethyl, -CH2C(=O)OR, -CH2C(=O)OC(=O)R, -CH2C(=S)OR, -CH2C(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CH2C(=O)R, -CH2C(=S)R, -CH2CF3, -CH2NO2, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl or any combination thereof; R6 is methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C 20 alkyl, 2,2,2-trisubstituted ethyl, -CHC(=O)OR, -CHC(=O)OC(=O)R, -CHC(=S)OR, -CHC(=O)SR, -C(=O)OR, -C(=O)OC(=O)R, -C(=S)OR, -C(=O)SR, -C(=O)-R, -C(=S)-R, -CHC(=O)R, -CHC(=S)R, -CHCF, -CHNO, terpenoid moiety, cycloalkyl, aryl, phenyl, benzyl, heterocycle, conjugated alkyl, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof.

[0252] In another embodiment, the same trialkoxysilane linker molecules (of Figures 12-13) are first used, albeit at a higher concentration (>10% wt), and first self-polymerized under base catalysis (Figures 12A and 13A, for standard particles and particles with enhanced thermal stability, respectively). Functionalization of the solid-supported linker proceeds similarly to the procedure described herein above for particles containing one monomer unit per unit of antimicrobial activity (Figures 4-9).

[0253] In some embodiments, the core of the process of Figures 10-13 already comprises (at least one) polymerizable unit covalently connected / bonded thereto (either directly or indirectly via a linker as described herein). In another embodiment, the particles obtained from the above process shown in Figures 10-13 are further reacted to obtain antimicrobial particles of the invention comprising at least one antimicrobial active unit and at least one polymerizable unit. In some other embodiments, the further reactions are detailed above in the sections entitled "Solid Support as a Method for Preparation of Antimicrobial Particles Comprising One Monomeric Unit per Antimicrobial Active Unit" and "Solution Method as a Method for Preparation of Antimicrobial Particles Comprising One Monomeric Unit per Antimicrobial Active Unit".

[0254] Solution method for the preparation of antimicrobial particles containing multiple monomer units per unit of antimicrobial activity. The solution method includes several stages. The first step involves the extension of the linker molecule. In another embodiment, this step is achieved synthetically through one or more steps. In another embodiment, the extension is achieved by successive additions of a difunctionalized alkane and a diaminoalkane, where the amines (of the linker and the diaminoalkane) attack the electrophilic center of the difunctionalized alkane (Figures 14 and 15, for standard particles and particles with enhanced thermal stability, respectively: steps 1 and 2). In another embodiment, such successive additions may be repeated 1 to 10 times. In the second step, an antimicrobially active group (usually attached to an alkylene chain) is grafted to the resulting extended linker. In another embodiment, the grafting is achieved when an amine on the extended linker attacks the acyl halide moiety of the molecule of the grafted antimicrobially active group (Figures 14 and 15, step 3). Finally, the extended antimicrobially active linker is attached to the core by its functionalization. In this step, in the case of standard particles, linker molecules (a few percent dilute solution) are condensed onto the particle surface (surface functionalization) by (acid-catalyzed) hydrolysis of the leaving groups, thus binding the linker to the core (Figures 14 and 15, step 4).

[0255] The process is illustrated in Figures 16-17 for silica standard particles functionalized with dimethylethylammonium, and similarly the process is illustrated in Figures 18-19 for thermally stable silica particles functionalized with dimethylbenzylammonium, but is applicable to other hydroxyl terminated cores and antimicrobially active groups. The process of Figures 14-19 is applicable to other hydroxyl terminated cores and antimicrobially active groups.

[0256] In another embodiment, the same trialkoxysilane linker molecules are first used, albeit at a higher concentration (≧10 wt%), and first self-polymerized under base catalysis (see, e.g., FIG. 12B and FIG. 13B for standard particles and particles with enhanced thermal stability, respectively). Functionalization of the linker proceeds similarly to the procedure described herein above for particles containing one monomer unit per antimicrobially active moiety (see, e.g., FIG. 4-FIG. 9).

[0257] In some embodiments, the core of the process of Figures 14-19 already comprises (at least one) polymerizable unit covalently connected / bonded thereto (either directly or indirectly via a linker as described herein). In another embodiment, the particles obtained from the above process shown in Figures 14-19 are further reacted to obtain antimicrobial particles of the invention comprising at least one antimicrobial active unit and at least one polymerizable unit. In some other embodiments, the further reactions are detailed above in the sections entitled "Solid Support as a Method for Preparation of Antimicrobial Particles Comprising One Monomeric Unit per Antimicrobial Active Unit" and "Solution Method as a Method for Preparation of Antimicrobial Particles Comprising One Monomeric Unit per Antimicrobial Active Unit".

[0258] In some embodiments, when it is noted herein that the core of the processes of Figures 4-19 already comprises (at least one) polymerizable unit covalently connected / bonded thereto (either directly or indirectly via a linker as described herein), it means that said polymerizable unit has been connected / bonded to the core by any one of the methods described above, e.g., in the sections entitled "Solid Support as a Method for Preparation of Antimicrobial Particles Comprising One Monomer Unit per Antimicrobial Activity Unit" and "Solution Method as a Method for Preparation of Antimicrobial Particles Comprising One Monomer Unit per Antimicrobial Activity Unit".

[0259] In one embodiment, the antimicrobial particles are prepared according to any one of the methods described above (having one or more monomer units per antimicrobial unit), and the actual polymerizable functional group comprises multiple functional polymerizable groups. See Z3 in formula (7). In another embodiment, a process similar to that described above is provided for obtaining said antimicrobial particles having Z3 comprising multiple functional polymerizable groups, where Z3 is linked as described above (Z3 is a "monofunctional" polymerizable group).

[0260] Preparation of core particles In some embodiments, particles of the composites of the invention comprising one or more monomer units per antimicrobially active moiety comprise a core prepared according to the following.

[0261] Porous silica materials can be prepared by reacting SiCl4 with alcohol or water, followed by drying using centrifugation and / or heating with the aid of airflow or under vacuum conditions. Dense fumed silica particles (pyrogenous) were prepared by pyrolysis of SiCl4.

[0262] An alternative method for the preparation of the silica core material can be by hydrolysis of tetraethyl orthosilicate (TEOS) or tetramethyl orthosilicate (TMS) under basic conditions (Stober) or under acidic catalytic conditions in the presence of alcohol or aqueous solutions.

[0263] Mesoporous silica particles can be prepared by hydrolysis of TEOS or TMS at low temperatures, for example at temperatures below 60° C., followed by dehydration by centrifugation and / or evaporation under air flow or vacuum conditions.

[0264] Dense particles can be prepared using intense heating in a process called calcination. Typically, such processes are carried out at high temperatures, around 250°C.

[0265] In some embodiments, the core is a POSS that does not require further functionalization; rather, the core already includes antimicrobially active units and polymerizable units attached thereto (via siloxane moieties).

[0266] In one embodiment, the present invention provides an antimicrobial particle comprising a POSS as a core and antimicrobially active units and polymerizable units attached to said POSS core via siloxane units of the POSS.

[0267] In one embodiment, the present invention provides a method for preparing an antimicrobial POSS, the method comprising: Optionally, alkylating the antimicrobial siloxane precursor with an alkylating agent to form a quaternary ammonium, a tertiary amine, or any combination thereof; - mixing an optionally alkylated antimicrobial siloxane precursor with a polymerizable siloxane precursor; - hydrolyzing the siloxane precursor to form an antimicrobial POSS; and - Providing work-up conditions to obtain antibacterial POSS particles.

[0268] In some embodiments, the antimicrobial siloxane precursor is of formula (IC) above. In one embodiment, the antimicrobial siloxane precursor is an alkyl-trialkoxysilane, trialkoxyarylsilane, trihaloalkylsilane, or trihaloarylsilane, where the alkyl or aryl is end-terminated with an antimicrobial group as described above. In another embodiment, the antimicrobial siloxane precursor is 3-aminopropyltriethoxysilane (APTES) or [3-(2-aminoethylamino)propyl]trimethoxysilane (AEAPTS).

[0269] In some embodiments, the polymerizable precursor is an alkyl-trialkoxysilane, trialkoxyarylsilane, trihaloalkylsilane, or trihaloarylsilane, where the alkyl or aryl is terminally terminated with Z3 in formula (7) above. In one embodiment, the polymerizable precursor is 3-(trimethoxysilyl)propyl acrylate.

[0270] In some embodiments, the alkylating agent is a C1-C20 alkyl functionalized with a leaving group selected from ethoxy, methoxy, sulfonate (e.g., mesyl, tosyl), and halide. In one embodiment, the alkylating agent is iodomethane or 1-iodooctane. In another embodiment, the alkylation is carried out first with a first alkylating agent and in a second step with a second alkylating agent. In another embodiment, alkylation is carried out first with 1-iodooctane and then with iodomethane in a second step.

[0271] In some embodiments, the hydrolysis is acidic or basic. In one embodiment, the hydrolysis is basic. In one embodiment, the hydrolysis is acidic. In one embodiment, the hydrolysis is basic and is carried out using any suitable base in the art (e.g., NaHCO3, NaOH, Na2CO3). In one embodiment, the hydrolysis is acidic and is carried out using any suitable acid in the art (e.g., HCl, HOAc, CF3CO2H).

[0272] In some embodiments, the work-up conditions can include any suitable technique known in the art, in one embodiment, the work-up includes lyophilization of the particles followed by mechanical trituration to provide dry antimicrobial POSS particles.

[0273] In some embodiments, the present invention provides antimicrobial POSS particles prepared according to any one of the above methods.

[0274] In some embodiments, provided herein are antimicrobial particles comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized with at least one quaternary ammonium group or at least one functional polymerizable group, and the molar ratio of silicon atoms functionalized with at least one quaternary ammonium group to silicon atoms functionalized with at least one functional polymerizable group is 10:1 to 1:10, respectively. In one embodiment, the POSS antimicrobial particles comprise antimicrobially active units and polymerizable units bound to said POSS core via siloxane units of the POSS.

[0275] In other embodiments, the methods of preparing antimicrobial particles provided herein include: mixing a first monomer unit comprising a trialkoxysilane linked to a quaternary ammonium group by a linker with a second monomer unit comprising a trialkoxysilane linked to a functional polymerizable group by a linker in a ratio of 10:1 to 1:10, respectively; and Hydrolyzing and polymerizing the first and second monomer units under basic conditions to form a POSS core functionalized with an antimicrobial group and a functional polymerizable group.

[0276] In some embodiments, the particles are prepared by hydrolysis of N-alkylated [3-(2-aminoethylamino)propyl]trimethoxysilane (AEAPTS) and 3-(trimethoxysilyl)propyl acrylate. In other embodiments, the hydrolysis is basic. In other embodiments, the N-alkylation of AEAPTS comprises alkylation with 1-iodoctane followed by alkylation with iodomethane.

[0277] Preparation of the Compositions of the Invention In some embodiments, the composites of the present invention are prepared by embedding antimicrobial particles in the polymeric material of the present invention. In other embodiments, one type of particle is embedded in the polymeric material. In other embodiments, a combination of different types of particles is embedded in the polymeric material. In some embodiments, embedding can be accomplished by a variety of methodologies.

[0278] In some embodiments, embedding of functionalized microparticles in polymeric materials is obtained by two methodologies: A) Extrusion technique: the particles are added to the molten thermoplastic polymer in an extruder, for example a twin-cone type extruder. B) The thermoplastic or thermosetting polymer is heated under reflux conditions in an organic solvent (non-limiting examples include xylene, toluene, their derivatives or any combination thereof) to achieve complete dissolution of the polymer. The antimicrobial particles are then dispersed in the same solvent used for the polymer, and the mixture is added to the dissolved polymer using an overhead stirrer or homogenizer. After complete dispersion of the particles in the polymer, the solvent is evaporated using conventional distillation or evaporation methods.

[0279] In some embodiments, embedding of functionalized microparticles in silicone-based polymeric materials is obtained by several methodologies: A) Room temperature vulcanization (RTV) of the silicone precursor is achieved, and the particles are incorporated into the unpolymerized or prepolymerized silicone, followed by final curing at a final concentration of 0.5-8% wt. particles per silicone polymer. In another embodiment, curing is activated by moisture. In another embodiment, curing is activated by heat. B) RTV of the silicone precursor is achieved, and polymerization is induced by mixing the two components of the polymerization mixture. In another embodiment, the particles are incorporated into both parts at a final concentration of 0.5-8% wt. particles per silicone polymer, or incorporated at double concentration in one part, resulting in a final concentration of 0.5-8% wt. particles per silicone polymer.

[0280] Thus, according to some embodiments, the present invention provides a method for preparing a composition comprising embedding a plurality of antimicrobial particles in a polymeric material as described above, the particles being embedded in the material, the method comprising adding the particles as described above into a molten polymeric material using extrusion, or into a polymeric solution in a solvent, or by polymerization with the particles and a polymer precursor. In one embodiment, the range of identical substituents (e.g., R1, R2, R3, etc.) in a particle found in a "plurality of particles" is the same as that shown above in all said particles, although the specific values ​​of each of the particles for the same substituent may be different. For example, in "particle #1" R1=methyl, but in "particle #2" R1=propyl, so that in this particular embodiment, particles 1-2 are different at least due to this.

[0281] In some embodiments, the particles according to the invention are uniformly distributed on the outer surface of the polymeric material with a surface concentration of about 0.1 to about 100 particles per sq. micrometer. In another embodiment, the particles according to the invention are uniformly distributed on the outer surface of the polymeric material with a surface concentration of about 1 to about 100 particles per sq. micrometer. The term "homogeneous distribution" is used to indicate a distribution characterized by a standard deviation of the number of particles per sq. micrometer being about the average number of particles per sq. micrometer. A uniform distribution can be advantageous for reproducibility and product specifications. If the distribution is not uniform, the product may exhibit different properties in different regions. The distribution of the particles away from the outer surface, i.e., their bulk concentration, can be similar to the distribution on the outer surface. In principle, the total surface of the particles may occupy at most about 20% of the surface of the material, for example, the total surface of the particles may occupy 1% to 15% of the surface of the material, or in some embodiments, 1% to 5%, or 1% to 3%.

[0282] According to some embodiments, on average there is at least one particle of the present invention per sq. micrometer of the outer surface of the polymeric material.

[0283] Compositions and methods of use thereof According to another aspect of the present invention, there is provided a method for inhibiting bacteria by contacting the bacteria with the antimicrobial particles of the present invention, or a composition or pharmaceutical composition comprising the particles or particles of the present invention.The term "inhibition" can refer to any of the following: destruction, e.g., eradication, of at least 99% of bacteria, at least 99.9% of bacteria, at least 99.99% of bacteria; reduction in the growth rate of bacteria; reduction in the size of the population of bacteria; prevention of bacterial growth; causing irreparable damage to bacteria; destruction of the biofilm of such bacteria; causing short-term or long-term damage to a part or whole of an existing biofilm; prevention of the formation of such biofilm; induction of biofilm control; or any other type of result that can affect such population or biofilm and impose immediate or long-term damage (partial or complete).

[0284] The term "biofilm" refers to a community of biological species (bacteria) attached to a solid surface.

[0285] In some embodiments, inhibition is achieved by contacting the bacteria with a matrix containing up to 5% w / w, or such as up to 1%, of particles according to the invention or compositions comprising them.

[0286] In one embodiment, the present invention further provides a composition or pharmaceutical composition comprising the antimicrobial particles described herein above. In another embodiment, the composition / pharmaceutical composition comprises one type of particle. In another embodiment, the composition / pharmaceutical composition comprises a combination of different types of particles. In one embodiment, non-limiting examples of compositions / pharmaceutical compositions of the present invention are dental adhesives, bone cements, dental restorative materials, such as any kind of composite-based materials for filling carious cavities, endodontic filling materials (cements and fillers) for filling root canal spaces in root canal treatment, materials used for provisional and definitive tooth restoration or replacement (including but not limited to inlays, onlays, crowns, partial dentures (fixed or removable), dental implants, as well as permanent and temporary cements used in dentistry for various known purposes, dental and orthopedic resin-based cements, sealers, composites, adhesives and cements, dental restorative composites, bone cements, toothpastes, lotions, hand sanitizers, ointments and creams used in the dermatology, wound care or beauty industry, plasticware for medical and research laboratories); food packaging, mainly for dairy products and raw meat and fish; pharmaceutical packaging to prevent biofilm growth or to treat, destroy and / or kill biofilms or bacteria therein, marine paints, bathroom paints, hospital and clean room paints; water filtration media, and many others. Each possibility represents a separate embodiment of the present invention. In some embodiments, the particles or compositions comprising same are used in dental and orthopedic resin-based cements, sealers, composites, adhesives and cements; dental and orthopedic metal implants and wires; surgical sutures; catheters, metal surgical instruments, non-surgical medical devices. Each possibility represents a separate embodiment of the present invention.

[0287] In one embodiment, the composition or composite of the present invention is a varnish or glaze that is applied to the surface of a tooth, dental restoration or crown containing the particles of the present invention. In another embodiment, the varnish or glaze is a protective coating, lacquer; providing a superficially polished appearance to the tooth surface, dental restoration or crown. In another embodiment, the varnish is a fluoride varnish, a highly concentrated form of fluoride that is applied to the tooth surface as a type of topical fluoride therapy. In another embodiment, the purpose of the glaze is to seal open pores on the surface of the fired porcelain. Dental glaze is composed of colorless glass powder and is applied to the surface of a fired crown to provide a glossy surface. Unglazed or trimmed porcelain can also result in irritation of the soft tissues it comes in contact with.

[0288] In one embodiment, the composition / pharmaceutical composition of the present invention is in a form selected from the group consisting of cream, ointment, paste, dressing and gel, for example, the composition is formulated for topical application or administration.In another embodiment, the composition is intended for administration into the oral cavity.The composition may be formulated as toothpaste and / or applied to a surface or medical device selected from the group consisting of denture cleaner, dressing or gel after hygiene treatment, mucoadhesive paste, dental adhesive, dental restorative composite-based material for filling caries cavities, dental restorative endodontic filling material for filling root canal space in root canal treatment, dental restorative material used for provisional and definitive tooth restoration or tooth replacement, dental inlay, dental onlay, crown, partial denture, complete denture, dental implant, and dental implant abutment.

[0289] In one embodiment, the pharmaceutical composition further comprises at least one pharmacoactive ingredient. In another embodiment, non-limiting examples of pharmacoactive ingredients include analgesics, antibiotics, anticoagulants, antidepressants, anticancer drugs, antiepileptic drugs, antipsychotic drugs, antiviral drugs, sedatives, and antidiabetic drugs. In another embodiment, non-limiting examples of analgesics include paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), morphine, and oxycodone. In another embodiment, non-limiting examples of antibiotics include penicillin, cephalosporins, ciprofloxacin, and erythromycin. In another embodiment, non-limiting examples of anticoagulants include warfarin, dabigatran, apixaban, and rivaroxaban. In another embodiment, non-limiting examples of antidepressants include sertraline, fluoxetine, citalopram, and paroxetine. In another embodiment, non-limiting examples of anti-cancer drugs include capecitabine, mitomycin, etoposide, and pembrolizumab. In another embodiment, non-limiting examples of anti-epileptic drugs include acetazolamide, clobazam, ethosuximide, and lacosamide. In another embodiment, non-limiting examples of anti-psychotic drugs include risperidone, ziprasidone, paliperidone, and lurasidone. In another embodiment, non-limiting examples of anti-viral drugs include amantadine, rimantadine, oseltamivir, and zanamivir. In another embodiment, non-limiting examples of sedative drugs include alprazolam, clorazepate, diazepam, and estazolam. In another embodiment, non-limiting examples of anti-diabetic drugs include glimepiride, gliclazide, glyburide, and glipizide.

[0290] In another embodiment, the pharmaceutical composition further comprises an excipient. In another embodiment, the excipient comprises a binder, a coating, a lubricant, a flavoring, a preservative, a sweetener, a vehicle, and a disintegrant. In another embodiment, non-limiting examples of binders include sugars, gelatin, polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG). In another embodiment, non-limiting examples of coatings include hydroxypropylmethylcellulose, polysaccharides and gelatin. In another embodiment, non-limiting examples of lubricants include talc, stearin, silica and magnesium stearate. In another embodiment, non-limiting examples of disintegrants include cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose (croscarmellose sodium) and modified sodium starch glycolate.

[0291] In one embodiment, the invention relates to a packaging composition comprising a thermoplastic polymer and / or hydrogel having embedded therein antimicrobial particles as described herein above. In another embodiment, the thermoplastic polymer and / or hydrogel is embedded with a mixture of two or more different particles. In another embodiment, the packaging composition is used for packaging food, beverages, pharmaceutical ingredients, medical devices, pre-operative surgical instruments, pre-operative instruments, cosmetics, and sterilized instruments / materials.

[0292] In one embodiment, the packaging composition comprises a thermoplastic polymer and / or hydrogel in which the particles described hereinabove are embedded. In another embodiment, the thermoplastic polymer is polyvinyl chloride (PVC), polyethylene, polypropylene, silicone, epoxy resin or acrylic polymer. In another embodiment, the thermoplastic polymer is polymethylmethacrylate or polyurethane.

[0293] In another embodiment, the packaging composition further comprises a binder, a coating, a lubricant, and a disintegrant. In another embodiment, non-limiting examples of binders include sugars, gelatin, polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG). In another embodiment, non-limiting examples of coatings include hydroxypropylmethylcellulose, polysaccharides and gelatin. In another embodiment, non-limiting examples of lubricants include talc, stearin, silica and magnesium stearate. In another embodiment, non-limiting examples of disintegrants include cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose (croscarmellose sodium) and modified sodium starch glycolate.

[0294] In one embodiment, the packaging composition is used to package pharmaceutical ingredients. In another embodiment, non-limiting examples of pharmaceutical ingredients include analgesics, antibiotics, anticoagulants, antidepressants, anticancer drugs, antiepileptic drugs, antipsychotic drugs, antiviral drugs, sedatives, and antidiabetic drugs. In another embodiment, non-limiting examples of analgesics include paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), morphine, and oxycodone. In another embodiment, non-limiting examples of antibiotics include penicillin, cephalosporins, ciprofloxacin, and erythromycin. In another embodiment, non-limiting examples of anticoagulants include warfarin, dabigatran, apixaban, and rivaroxaban. In another embodiment, non-limiting examples of antidepressants include sertraline, fluoxetine, citalopram, and paroxetine. In another embodiment, non-limiting examples of anti-cancer drugs include capecitabine, mitomycin, etoposide, and pembrolizumab. In another embodiment, non-limiting examples of anti-epileptic drugs include acetazolamide, clobazam, ethosuximide, and lacosamide. In another embodiment, non-limiting examples of anti-psychotic drugs include risperidone, ziprasidone, paliperidone, and lurasidone. In another embodiment, non-limiting examples of anti-viral drugs include amantadine, rimantadine, oseltamivir, and zanamivir. In another embodiment, non-limiting examples of sedative drugs include alprazolam, clorazepate, diazepam, and estazolam. In another embodiment, non-limiting examples of anti-diabetic drugs include glimepiride, gliclazide, glyburide, and glipizide.

[0295] In one embodiment, the packaging composition is used to package food ingredients. In another embodiment, non-limiting examples of food ingredients packaged with the packaging material of the present invention include fresh produce, preservatives, sweeteners, color additives, flavors and spices, nutrients, emulsifiers, binders and thickeners. In another embodiment, non-limiting examples of fresh produce include meat, poultry, fish, dairy products, fruits and vegetables. In another embodiment, non-limiting examples of preservatives include ascorbic acid, citric acid, sodium benzoate, calcium propionate, sodium erythorbate, butylated hydroxytoluene (BHT), silver, chlorhexidine, triclosan and sodium nitrite. In another embodiment, non-limiting examples of sweeteners include sucrose (sugar), glucose, fructose, sorbitol, mannitol and corn syrup. In another embodiment, non-limiting examples of color additives include orange B, citrus red No. 2, annatto extract, beta carotene, grape skin extract, cochineal extract or carmine and paprika oleoresin. In another embodiment, non-limiting examples of flavors and spices include monosodium glutamate, glycine sulphate, inosinic acid, isoamyl acetate, and limonene and allyl hexanoate. In another embodiment, non-limiting examples of nutrients include thiamine hydrochloride, riboflavin (vitamin B2), niacin, niacinamide, folate or folic acid. In another embodiment, non-limiting examples of emulsifiers include soy lecithin, mono- and diglycerides, egg yolk, polysorbate and sorbitan monostearate. In another embodiment, non-limiting examples of binders and thickeners include gelatin, pectin, guar gum, carrageenan, xanthan gum and whey.

[0296] In one embodiment, the present invention provides a method of inhibiting or preventing biofilm formation comprising applying a composition of the present invention to a susceptible or infected surface or medical device.

[0297] In another embodiment, the present invention provides a composition of the invention for use in inhibiting or preventing biofilm formation.

[0298] In one embodiment, the present invention provides a method of inhibiting or preventing the formation or growth of a biofilm, comprising placing a medical device of the present invention (comprising a composition of the present invention as referred to herein above) on the surface to be treated, hi another embodiment, the medical device is a wound dressing.

[0299] In another embodiment, the present invention provides a medical device of the present invention for use in inhibiting or preventing biofilm formation or growth.

[0300] In one embodiment, the invention provides a method of inhibiting bacteria, the method comprising the step of contacting the bacteria with a pharmaceutical composition or packaging composition or complex of the invention.

[0301] In another embodiment, the present invention provides a pharmaceutical or packaged composition for use in inhibiting bacteria.

[0302] In one embodiment, the present invention provides a method for treating, disrupting or killing biofilms or internal bacteria, the method comprising applying a pharmaceutical composition or packaging composition or composite of the present invention onto a susceptible or infected surface or medical device.

[0303] In another embodiment, the present invention provides a complex or a pharmaceutical composition or a packaged composition of the present invention for use in treating, disrupting or killing bacteria within a biofilm or within a biofilm.

[0304] Applications from the medical field can be, for example, clothing (e.g. for sports or outdoor activities; preventing sweat odor induced by bacteria), sports shoes or the inner parts of shoes where bacteria tend to collect, sportswear and clothing for outdoor activities, toothbrushes and any brushes that come into contact with the human body, air and water filters, water treatment and distribution systems, pet cages and other veterinary supplies, etc.

[0305] In some embodiments, the antimicrobial compositions or complexes of the invention are effective in killing at least about 99% of bacteria on contact, or in some embodiments, at least about 99.9% or 99.99% of bacteria on contact.

[0306] Even more surprisingly, it has been discovered that the particles within the compositions / composites / medical devices of the present invention maintain high antimicrobial properties over time without leaching or altering the properties of the hosting matrix. Such particles exhibit enhanced antimicrobial activity due to the presence of densely packed antimicrobial groups on the surface of a given particle.

[0307] Medical Device of the Present Invention In one embodiment, the present invention further provides a medical device comprising the composition of the present invention. In one embodiment, non-limiting examples of medical devices of the present invention are catheters, stents, surgical meshes, breast implants, artificial joints, artificial bones, artificial blood vessels, artificial heart valves (cardiology), artificial skin, plastic surgery implants or prostheses, intrauterine devices (gynecology), neurosurgical shunts, contact lenses (ophthalmology), intraocular lenses, intraocular prostheses, urethral stents, coatings for subcutaneous implants (such as orthopedic or dental), insulin pumps, contraceptives, pacemakers, tubes and cannulas used for intravenous infusion, tubes and cannulas used for dialysis, surgical drainage tubes, urinary catheters, endotracheal tubes, wound coverings (dressings and bandages) and treatments (e.g. For example, gels, ointments, pastes and creams for wound care to reduce biofilm and bacteria and promote wound healing, sutures, catheters of all kinds temporarily or permanently inserted into the vascular and urinary systems, shunts for use in cerebral applications, surgical gloves, tips for ear examinations, the ends of statoscopes and other elements used by medical practitioners; toothbrushes, toothpicks, dental floss, interdental and tongue brushes, surgical sutures, metal surgical instruments, non-surgical medical devices, dental and orthopedic metal implants and wires, as well as surgical drains, syringes, trays, tips, gloves and other accessories used in general medical and dental procedures.

[0308] In one embodiment, the present invention further provides a medical device comprising a dental appliance. In one embodiment, the present invention further provides a medical device comprising an orthodontic appliance. The dental appliance and orthodontic appliance comprise the particles and compositions of the present invention. In some embodiments, the orthodontic appliance comprises aligners, brackets, dental attachments, bracket auxiliaries, ligature ties, pins, bracket slot caps, wires, screws, microstaples, cements for brackets and attachments, and other orthodontic appliances, dentures, partial dentures, dental implants, periodontal probes, periodontal chips, films, or interdental spaces for promoting tooth alignment. In some embodiments, the dental appliance may comprise mouth guards, night guards, used to prevent tooth grinding (bruxer), oral devices used to treat / prevent sleep apnea, and tooth guards used in sports activities.

[0309] In one embodiment, the present invention further provides percutaneous medical devices, such as orthopedic external fixation screws, and wires used for bone fixation and stabilization, as well as transmucosal elements used in dental implants, for screw or cement-retained dental prostheses, such as healing caps, abutments (multi-unit, etc.).

[0310] In one embodiment, the invention further provides medical devices including, but not limited to, endoscopes (rigid and flexible), including colonoscopes, gastroscopes, duodenoscopes, bronchoscopes, cystoscopes, ENT scopes, laparoscopes, laryngoscopes, and similar instruments for examining or treating inside a patient's body (including any part thereof), as well as accessories and other devices used in procedures that come into contact with bodily tissues or fluids; tubes, pumps, containers and connectors (used inside or outside the body) through which fluids, air or gases are pumped into or drawn out of the patient and which may be contaminated by the patient or transfer contaminants from other patients; items such as brushes, trays, covers, tubes, connector cabinets, and bags used in reprocessing, cleaning, transporting, and storing such equipment and which may transfer and receive biological contaminants, as well as filters for air or water used in dental or medical procedures, hospital exteriors (floors, tabletops, etc.), drapes, curtains, linens, handles, etc.

[0311] The antimicrobial properties can protect patients and medical staff from cross-contamination from patient to patient or from patient to examiner. Self-sterilizing packaging of medications and items entering the operating room is also beneficial.

[0312] In one embodiment, the present invention further provides a method for preparing a medical device comprising the composite. In another embodiment, the medical device is prepared by providing a fluid phase of the composite of the present invention; molding the fluid; and hardening the molded fluid to obtain the desired medical device. In another embodiment, the medical device is prepared by providing a solid phase of the composite; and molding the solid to obtain the desired medical device. In another embodiment, molding is accomplished by extrusion or molding. In another embodiment, the fluid phase of the composite comprises a molten composite or a composite dissolved in a solvent.

[0313] Another polymeric material used in the context of the present invention is the resin used in dental, surgical, chirurgical and orthopedic composites. In such applications, the antimicrobial particles can be initially dispersed within the resin part or added simultaneously with the filler or any other solid components (if any). Most of these resins are acrylic or epoxy type monomers that are polymerized in vivo.

[0314] In some embodiments, the terms "antimicrobial" and "antibacterial" are used interchangeably herein.

[0315] The following examples are presented in order to more fully illustrate the preferred embodiments of the invention, but they should in no way be construed as limiting the broad scope of the invention.

[0316] [Example] [Example 1] Preparation of QASi-PF particles (without acrylate) [3-(2-aminoethylamino)propyl]trimethoxysilane (AEAPTS) (1 eq.; 10% w / w in THF) was reacted with 1-iodooctane (2 eq.) and then with iodomethane (4 eq.) to convert all amines to hydrophobic quaternary ammonium groups. The silane groups were then hydrolyzed in aqueous NaHCO3 and subsequently condensed to form the POSS particles.

[0317] Dry POSS particles were obtained by freeze-drying followed by mechanical trituration.

[0318] [Example 2] Preparation of QASi-PA particles (with acrylate) [3-(2-aminoethylamino)propyl]trimethoxysilane (AEAPTS) (1 eq.; 10% w / w in THF) was reacted with 1-iodooctane (2 eq.) and then with iodomethane (4 eq.) to convert all amines to hydrophobic quaternary ammonium groups. 3-(Trimethoxysilyl)propyl acrylate (0.25 eq.) was added to the solution. The silane groups were then hydrolyzed in aqueous NaHCO3, followed by condensation to form POSS particles. Dry POSS particles were obtained by freeze-drying followed by mechanical trituration.

[0319] [Example 3] Preparation of dental composite Resin preparation: Bisphenol A glycidyl ether dimethacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA) were mixed together until a clear blend was obtained. 0.1% camphorquinone (CQ), 0.1% benzoin methyl ether (BME), 0.1% ethyl 4-(dimethylamino)benzoate (EDB) and 0.01% butylated hydroxytoluene (BHT) were added and mixed until completely dissolved.

[0320] Compounding: Glass powder was added to the prepared resin to give a ratio of 78.5% filler, 20% resin, and 1.5% QASi particles (Example 1 or Example 2). The composite was mixed under vacuum using a planetary kneader until it became a uniform paste.

[0321] [Example 4] Particle Leaching Testing - Verification The following validates the limit tests for detecting QASi in polar and non-polar extractions. During the study, specificity and detection limits were verified using ISO 10993-12 and 18 sample preparation and biological evaluation guidelines. A HPLC / MS (High Performance Liquid Chromatography Mass Spectrometry) system was used (Agilent 1260 HPLC coupled with LC / MS Triple Quad) with standard laboratory equipment and reagents (water, acetonitrile, formic acid, ethanol and NaCl 0.9%), with which an analytical method for analyte quantification was developed.

[0322] A 500 μg / ml MS1 standard solution of QASi-PF was prepared using approximately 12.5 mg of dissolved particles and diluted to 25 ml with ethanol. The dilutions were as shown in the table below. [Table 1] A 500 μg / ml MS2 standard solution of QASi-PA was prepared using approximately 12.5 mg of dissolved particles and diluted to 25 ml with ethanol. The dilutions were as shown in the table below. [Table 2] A preliminary scan in ESI+ mode from m / z 100 to m / z 1000 was performed to find the precursor ion for each reference. An ion signal of 266.3 m / z was found for QASi-PF and an ion signal of 273.2 m / z was found for QASi-PA. The samples were tested using the following conditions, and under these conditions, 1 μg / ml of sample was detected in both solvents without any interfering signals. [Table 3] It was therefore concluded that the method can assess the presence of masses of 266.3 and 273.2 not present in the solvent blank to verify the presence of QASi leaching from the extracted device.

[0323] [Example 5] Leaching Tests of QASi-PF and QASi-PA Particles (Examples 1 and 2, respectively) in Dental Composites (Composite Materials for Filling Cavities and Restoring Teeth) Particles were prepared as in Examples 1 and 2, compositions were prepared as in Example 3, and leachability testing was performed as in Example 4. The following solutions and concentrations were used: [Table 4] As exemplified below, lower leachability of QASi-PA particles (with acrylate) was demonstrated compared to QASi-PF particles (without acrylate), which were more easily removed from the matrix.

[0324] The results for QASi-PA particles (with acrylate) for both types of solutions are below, including the conclusion that extraction of QASi-PA must be considered exhaustive at 120 hours with ethanol:water and 96 hours with saline. A total of 268.2 μg / g QASi-PA was leached by ethanol:water, while no QASi-PA was leached by saline at the exhaustive conditions. Thus, QASi-PA particles (with acrylate) were shown to have low leachability from the matrix.

[0325] QASi-PA results: [Table 5] [Table 6] QASi-PF results (control): Extraction of QASi-PF must be considered exhaustive at 96 h for both extraction solvents. A total of 1454.4 μg / g QASi-PF was leached by ethanol:water, but no QASi-PF was leached by saline under exhaustive conditions. [Table 7] [Table 8] Thus, leaching in particles without acrylate (>1400 mg / g) was much more significant than the corresponding value in particles with acrylate (268.2 mg / g).

[0326] [Example 6] Leaching Test of QASi-PA Particles (Example 2) in Bond (Dental Adhesive for Fixing Direct and Indirect Dental Restorations) The leachability test provided in Example 4 was carried out to detect the QASi of the test items after exhaustive extraction with NaCl 0.9% and water:ethanol 50:50 solution according to ISO10993-12 guidelines. A disk of the bonded material was fully immersed in the extraction solvent using a solvent ratio of 0.2g / ml. Two solvents, NaCl 0.9% and water / ethanol (50 / 50), were used and the samples were kept at the following conditions: (i) 50±2°C for 72±2 hours, (ii) 50±2°C for 96±2 hours, and (iii) 50±2°C for 120±2 hours (only tested if exhaustion was not reached at 96 hours). A volume of each mixture was left in the same conditions as the sample used as a blank. The following solutions were used: MS1 standard solution 500 μg / ml containing approximately 12.5 mg of QASi-PA dissolved and diluted to 25 ml with ethanol; MS2 standard solution 20 μg / ml (ethanol:water 50:50) containing 0.2 ml of MS1 diluted to 5 ml with 50:50 ethanol:water; and MS2 standard solution 20 μg / ml (NaCl 0.9%) containing 0.2 ml of MS1 diluted to 5 ml with NaCl 0.9%. [Table 9] Sample preparation - Samples were injected without further treatment or after dilution if necessary. For 1:100 dilution, 0.1 ml of each extraction solution was diluted to 10 ml with the same extraction solvent. For 1:10 dilution, 0.1 ml of each extraction solution was diluted to 1 ml with the same extraction solvent. The leachability test setup was the same as in Example 4.

[0327] The results are shown in the table below: Extraction of QASi-PA must be considered exhaustive at 96 hours in ethanol:water and at 120 hours in saline.

[0328] A total of 436.5 μg / g QASi-PA was leached by ethanol:water and 66.8 μg / g QASi-PA was leached by saline under exhaustive conditions. [Table 10] [Table 11] [Example 7] Preparation of QASi-PV particles (containing silicone rubber) [3-(2-aminoethylamino)propyl]trimethoxysilane (AEAPTS) (1 eq.; 10% w / w in THF) was reacted with 1-iodooctane (2 eq.) and then with iodomethane (4 eq.) to convert all amines to hydrophobic quaternary ammonium groups. Vinyltrimethoxysilane (0.25 eq.) was added to the solution. The silane groups were then hydrolyzed in aqueous NaHCO3, followed by condensation to form POSS particles. Dry POSS particles were obtained by freeze-drying followed by mechanical pulverization.

[0329] Preparation of silicone rubber Composite compounding: Pt-catalyzed silicone rubber was prepared by mixing unpolymerized silicone with 2% wt / wt of QASi-PV, then cured at 80° C. for 2 h.

[0330] A control sample containing 2% wt / wt of QASi-PF was prepared simultaneously under the same conditions.

[0331] Leachability Test A 10 gr sample of each silicone (test and control) was immersed in 25 ml saline and maintained at 37°C for 72 hours. The liquid was then collected and examined using a UV spectrophotometer. To determine the correlation of UV absorbance intensity to QASi concentration in the liquid, a calibration curve of standard concentrations in saline was prepared and tested using the same UV spectrophotometer.

[0332] The results show that the particles remain in the silicone matrix with a QASi-PV concentration in saline after 72 hours: 0 mg per 10 gr silicone sample, in contrast to a QASi-PF (control) concentration in saline after 72 hours: 25 mg per 10 gr silicone sample, indicating leaching of the control particles (no vinyl groups).

[0333] [Example 8] Preparation of QASi-PE particles (containing epoxy) [3-(2-aminoethylamino)propyl]trimethoxysilane (AEAPTS) (1 eq.; 10% w / w in THF) was reacted with 1-iodooctane (2 eq.) and then with iodomethane (4 eq.) to convert all amines to hydrophobic quaternary ammonium groups. (3-glycidyloxypropyl)trimethoxysilane (0.25 eq.) was added to the solution. The silane groups were then hydrolyzed in aqueous NaHCO3 followed by condensation to form POSS particles. Dry POSS particles were obtained by freeze-drying followed by mechanical trituration.

[0334] Epoxy resin sample preparation Compounding of the composite: Diglycidyl ether of bisphenol-a (DGEBA) resin was mixed with diethylenediamine crosslinker (DETA) in a 5:1 ratio, and QASi-PE particles were added to adjust the total to 2% wt / wt, and mixed using an overhead stirrer. The sample was polymerized at 37 °C for 24 h.

[0335] A control sample containing 2% wt / wt of QASi-PF was prepared simultaneously under the same conditions.

[0336] Leachability Test A 12 gr sample of each silicone (test and control) was immersed in 25 ml saline and maintained at 37°C for 72 hours. The liquid was then collected and examined using a UV spectrophotometer. To determine the correlation of UV absorbance intensity to QASi concentration in the liquid, a calibration curve of standard concentrations in saline was prepared and tested using the same UV spectrophotometer.

[0337] The results showed that the QASi-PE concentration in saline after 72 hours was 25 mg per 12 gr silicone sample, indicating that the majority of the particles remained in the silicone matrix, in contrast to the QASi-PF (control) concentration in saline after 72 hours: 250 mg per 12 gr silicone sample, indicating leaching of the control particles (no epoxy groups).

[0338] While certain features of the invention have been illustrated and described herein, many modifications, substitutions, changes, and equivalents will occur to those skilled in the art. It is therefore to be understood that the appended claims are intended to cover all such modifications and changes that fall within the true spirit of the invention.

Claims

1. 1. An antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein silicon atoms of the POSS are functionalized with at least one antimicrobial group and at least one functional polymerizable group; the at least one functional polymerizable group comprises an acrylate, epoxy, vinyl, or isocyanate group; the molar ratio of the silicon atoms functionalized with the at least one antimicrobial group to the silicon atoms functionalized with the at least one functional polymerizable group is 10:1 to 1:10, respectively.

2. The antimicrobial particle of claim 1 , wherein the at least one antimicrobial group comprises a quaternary ammonium, a tertiary ammonium, or a tertiary amine.

3. 3. The antimicrobial particle of claim 2, wherein the at least one quaternary ammonium group is N-alkylated 3-(2-aminoethylamino)propyl, with a propyl end group attached to the silicon atom.

4. 4. The antimicrobial particle of claim 3, wherein the N-alkylated 3-(2-aminoethylamino)propyl comprises C1-C18 alkyl units, and at least one alkyl unit is a C4-C8 alkyl.

5. 2. The antimicrobial particle of claim 1, wherein the acrylate is propyl acrylate, with a propyl end group attached to a silicon chain.

6. The antimicrobial particles of claim 1, wherein the molar ratio is from 4:1 to 1:

1.

7. The antimicrobial particle of claim 1 , wherein the molar ratio is 4:

1.

8. The antimicrobial particle of claim 2 , wherein the quaternary ammonium comprises a C1-C18 alkyl unit.

9. The antimicrobial particle of claim 8, wherein at least one alkyl is a C4-C8 alkyl.

10. 10. The antimicrobial particles of claim 1, prepared by hydrolysis of N-alkylated [3-(2-aminoethylamino)propyl]trimethoxysilane (AEAPTS) and 3-(trimethoxysilyl)propyl acrylate.

11. The antimicrobial particle of claim 10 , wherein the hydrolysis is basic.

12. The antimicrobial particle of claim 10, wherein the N-alkylation of AEAPTS comprises alkylation with 1-iodoctane followed by alkylation with iodomethane.

13. The antimicrobial particle of claim 1 , wherein the at least one functional polymerizable group comprises an epoxy group.

14. The antimicrobial particle of claim 13, wherein the epoxy group is a substituted or unsubstituted 3-glycidyloxypropyl.

15. The antimicrobial particle of claim 1 , wherein the at least one functional polymerizable group comprises a vinyl group.

16. 16. The antimicrobial particle of claim 15, wherein the vinyl group is a substituted or unsubstituted vinyltrimethoxysilane.

17. 10. The antimicrobial particle of claim 1, wherein up to 70% of the silicon atoms of the POSS are capped.

18. 18. The antimicrobial particle of claim 17, wherein 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, or an intermediate proportion of the silicon atoms are capped using substituted or unsubstituted methylated, butyl, benzyl, and / or propyl groups.

19. A composition comprising a plurality of antimicrobial particles according to any one of claims 1 to 16 and a polymeric material as a matrix.

20. 20. The composition of claim 19, wherein the antimicrobial particles are uniformly dispersed in the polymeric material.

21. 21. The composition of claim 20, wherein the polymeric material comprises an organic polymer, an inorganic polymer, or any combination thereof.

22. 22. The composition of claim 21, wherein the organic polymer comprises a hydrogel, a polyolefin, an epoxy resin, an acrylate resin, or any combination thereof.

23. 23. The composition of claim 22, wherein the organic polymer comprises an epoxy resin and the at least one functional polymerizable group comprises an epoxy.

24. The composition of claim 23, wherein the epoxy is a substituted or unsubstituted 3-glycidyloxypropyl.

25. 22. The composition of claim 21, wherein the inorganic polymer comprises a silicone polymer ceramic, a metal, or any combination thereof.

26. 26. The composition of claim 25, wherein the inorganic polymer comprises at least one silicone polymer.

27. 27. The composition of claim 26, wherein the at least one functional polymerizable group comprises vinyl.

28. 28. The composition of claim 27, wherein the vinyl is a substituted or unsubstituted vinyltrimethoxysilane.

29. 26. The composition of claim 25, wherein the weight ratio of the antimicrobial particles to the polymeric material is 0.25 to 5%.

30. 20. The composition of claim 19, comprising a mixture of different antimicrobial particles.

31. 20. The composition of claim 19, wherein up to 70% of the silicon atoms of the POSS are capped.

32. 32. The composition of claim 31, wherein 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, or an intermediate percentage of the silicon atoms are capped using substituted or unsubstituted methylated, butyl, benzyl, and / or propyl groups.

33. 20. The composition of claim 19, which is capable of filling carious cavities and is selected from the group consisting of dental restorative endodontic filling materials for filling root canal spaces in root canal treatments or dental restorative materials intended for temporary and definitive tooth restoration or tooth replacement, dental inlays, dental onlays, crowns, partial dentures, complete dentures, dental implants, dental implant abutments, and cements intended for permanently bonding crowns, bridges, onlays, partial dentures and orthodontic appliances onto tooth enamel and dentin.

34. 20. The composition of claim 19, further comprising a filler.

35. 35. The composition of claim 34, comprising 78.5% w / w filler and 20% w / w resin.

36. 36. The composition of claim 35, wherein the resin is prepared by mixing bisphenol A glycidyl ether dimethacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA), and urethane dimethacrylate (UDMA) to obtain a clear blend, followed by mixing in camphoquinone (CQ), benzoin methyl ether (BME), ethyl 4-(dimethylamino)benzoate (EDB), and butylated hydroxytoluene (BHT) to obtain the resin.

37. 1. An antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein silicon atoms of the POSS are functionalized with at least one antimicrobial group and at least one functional polymerizable group; the at least one functional polymerizable group comprises a substituted and / or unsubstituted acrylate group, a substituted and / or unsubstituted epoxy group, a substituted and / or unsubstituted vinyl group, and / or an isocyanate group; The antibacterial active unit has the structure (1): 【Chemistry 1】 wherein: L １ is a first linker or bond, L ２ is a second linker, L ３ is a third linker or bond, R １ and R １ each ' is independently alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R ２ and R ２ each ' is independently alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; R ３ and R ３ each ' is independently nothing, hydrogen, alkyl, a terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl, or any combination thereof; R ３ or R ３ If there is no ', the nitrogen is uncharged, X １ and X ２ are each independently a bond, alkylene, alkenylene, or alkynylene; n １ are each independently an integer from 0 to 200, n ２ are each independently an integer from 0 to 200, n １ +n ２ ≧1; m is an integer from 1 to 200, and the repeat units are the same or different; 「 【Chemistry 2】 " concept refers to the covalent bonding to an organic or inorganic core, antimicrobial particles. In another embodiment, the antimicrobial group is —N(R １ ) (R ２ ) (R ３ ) ＋ , -N(R １ ) (R ２ ) ＋ -, -N(R １ ') (R ２ ') (R ３ ') ＋ or -N(R １ ') (R ２ ') ＋ - (All possibilities are X １ or X ２ covalently bonded to

38. 38. A composition comprising a plurality of the antimicrobial particles of claim 37 and a polymeric material as a matrix.

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