Functionalized antimicrobial particles

Abstract

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

Description

Field of the Invention

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

[0003] The overwhelming diversity of bacteria in the skin, gastrointestinal tract, and oral cavity of an individual is well documented, demonstrating anatomically and dynamically complex ecosystems in which poly-microbial biofilms are the norm.

[0004] Biofilms formed on tissues inside and outside an organism 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 are formed on both natural and artificial surfaces.

[0005] Artificial surfaces that come into contact with living organisms have received particular attention in recent years, since these surfaces lack epithelial shedding, the main natural mechanism against biofilms, and biofilm accumulation is therefore becoming a major source of medical problems that can lead to life-threatening complications. Two main factors influence the susceptibility of a surface to the accumulation of bacteria: surface roughness and surface free energy, which are properties of the material used. Surface roughness has a greater impact on bacterial adhesion than surface free energy. In this context, artificial repair materials usually have a higher surface roughness than natural surfaces and are therefore more susceptible to bacterial accumulation. Therefore, the development of new materials that reduce biofilm formation is a key topic.

[0006] The ultimate goal of developing materials with anti-biofilm properties is to improve health and reduce disease. None of the existing medical devices can guarantee immediate and complete elimination of biofilms or prevention of secondary infections.

[0007] For example, to maintain oral defense, dental materials with the following anti-biofilm properties are sought after the following steps: (1) inhibiting the initial binding of microorganisms, (2) preventing biofilm growth, (3) affecting the metabolism of microorganisms in the biofilm, (4) killing biofilm bacteria, and (5) detaching biofilms (Busscher HJ, Rinastiti M, Siswomihardjo W, van der Mei HC., JDent Res, 2010; 89: 657-65; Marsh PD. J Dent, 2010; 38).

[0008] Quaternary ammonium compounds (QACs) are widely used in the disinfection of water, surfaces and instruments and in the textile, leather and food industries due to their relatively low toxicity, wide antimicrobial spectrum, non-volatility and chemical stability. As disclosed in U.S. Patent No. 11,134,676 and U.S. Patent No. 11,178,867, antimicrobial particles based on quaternary ammonium groups have been developed. However, resin-based composites containing such antimicrobial particles result in leaching from the resin-based composites, and thus result in a reduction in antimicrobial activity and an increased risk of higher toxicity.

[0009] The present invention provides antimicrobial particles and resin-based composite materials containing the antimicrobial particles that have reduced leaching properties and still maintain antimicrobial activity. SUMMARY OF THE INVENTION

[0011] The following is a brief summary to provide an initial understanding of the present invention. This summary does not necessarily identify key elements nor limit the scope of the present invention, but merely serves as an introduction to the following description.

[0012] One aspect of the present invention provides an antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized by at least one antimicrobial group or by at least one functional polymerizable group, wherein the functional polymerizable group comprises 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 by at least one antimicrobial group to silicon atoms functionalized by at least one functional polymerizable group is between 10:1 and 1:10, respectively.

[0013] One aspect of the present invention provides an antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein the silicon atoms of the POSS are functionalized by at least one antimicrobial group and by at least one functional polymerizable group,

[0014] wherein at least one functional polymerizable group comprises a substituted and / or unsubstituted acrylate group, epoxy group, vinyl group and / or isocyanate group; and

[0015] The antimicrobial active unit is represented by structure (1):

[0016]

[0017] in

[0018] L1 is the first linker or bond;

[0019] L2 is the second linker;

[0020] L3 is the third linker or bond;

[0021] R1 and R1' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0022] R2 and R2' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0023] R3 and R3' are each independently none, hydrogen, alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; wherein if R3 or R3' is none, the nitrogen is uncharged;

[0024] X1 and X2 are each independently a bond, an alkylene group, an alkenylene group or an alkynylene group;

[0025] n1 is each independently an integer between 0 and 200;

[0026] n2 are each independently an integer between 0 and 200;

[0027] Where n1+n2≥1;

[0028] m is an integer between 1 and 200, and the repeating units are the same or different; and

[0029] Notion Represents a covalent bond to an organic or inorganic core.

[0030] In another embodiment, the antimicrobial group is -N(R1)(R2)(R3) + 、-N(R1)(R2)+ -、-N(R1')(R2')(R3') + or -N(R1')(R2') + -(all possible groups are covalently linked to X1 or X2).

[0031] One aspect of the present invention provides a composition comprising more than one disclosed antimicrobial particle and a polymeric material as a matrix.

[0032] These, additional and / or other aspects and / or advantages of the invention are set forth in the detailed description which follows; can be inferred from the detailed description; and / or can be learned by practice of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] The subject matter which is regarded as the invention is particularly pointed out and distinctly claimed in the concluding portion of the specification. However, the invention, both as to its organization and method of operation, together with objects, features, and advantages thereof, may be best understood by reference to the following detailed description when read with the accompanying drawings, in which:

[0035] Figure 1A-Figure 1C Schemes of an antimicrobial particle of the invention are depicted, according to some embodiments of the invention, the antimicrobial particle comprising one or more anti-microbial active unit(s) and one or more polymerizable unit(s). Figure 1A : particles having the same number of antimicrobial active units and polymerizable units (6); Figure 1B : particles having more antimicrobially active units than polymerizable units (7 compared to 5, respectively); and Figure 1C : particles having more polymerizable units than antimicrobially active units (7 compared to 5, respectively). Figure 1A-Figure 1C In the drawings, it can be seen that the (antimicrobially active and polymerizable) units may be identical or different, as can be inferred from the term ". . . unit 1" or ". . . unit 2".

[0036] Figure 2A-2B Antimicrobially active units and (antimicrobial) monomer units according to some embodiments of the invention are depicted. Figure 2A : antimicrobial activity unit; and Figure 2B :(antimicrobial) monomer unit; the concept Defined as a bond to the inorganic or organic core of the antimicrobial particles of the present invention.

[0037] Figure 3A-3BDepicted are polymerizable units and (polymerizable) monomer units according to some embodiments of the invention. Figure 3A : polymerizable unit; and Figure 3B :(polymerizable) monomer unit; the concept Defined as a bond to the inorganic or organic core of the antimicrobial particles of the present invention.

[0038] Figure 4 Depicted is a representative scheme for preparing standard particles according to some embodiments of the present invention, wherein the antimicrobial active group is a tertiary amine or quaternary ammonium group comprising at least one terpenoid moiety, and the antimicrobial unit has one monomer unit (monomer backbone); the circle represents an organic core or an inorganic core; and R 1 -YR 1 is C1-C4 alkyl, and Y is a leaving group such as halogen or sulfonate.

[0039] Figure 5 Depicted is a representative scheme for preparing standard particles according to some embodiments of the present invention, wherein the particles have a cinnamyl group with a core (represented by a circle) via an amino functional linker, wherein 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 tertiary amine and the group R 1 -Y reaction, where R 1 is C1-C4 alkyl, and Y is a leaving group such as halogen or sulfonate.

[0040] Figure 6A-6C Depicted are representative schemes of three approaches for preparing quaternary ammonium salt (QAS) functionalized standard particles according to some embodiments of the present invention, wherein the antimicrobial unit has one monomer unit (monomer backbone); circles represent either an organic core or an inorganic core. Fig. 6A ) by reductive amination to obtain a tertiary amine, followed by an alkylation reaction; Figure 6B ) by a stepwise alkylation reaction; and Figure 6C ): by reacting a linker functionalized with a leaving group (eg, Cl or another halogen) with a tertiary amine. 1 and R 2 represents a C1-C4 alkyl group such as methyl, ethyl, propyl or isopropyl. 1 and R 2 They may be different groups or the same group. Y represents any leaving group, such as Cl, Br or I, or a sulfonate (eg, mesyl, tosyl).

[0041] Figure 7A-7CDepicted are representative schemes of three approaches for preparing quaternary ammonium salt (QAS) functionalized particles with enhanced thermal stability, wherein the antimicrobial unit has one monomer unit (monomer backbone) according to some embodiments of the present invention. The circles represent either an organic core or an inorganic core. Fig. 7A ) by alkylation with R1-Y / R2-Y to obtain a tertiary amine, followed by a benzylation reaction; Figure 7B ) is accomplished by a similar approach as in A), but in reverse order; and Figure 7C ): by reacting a linker functionalized with a leaving group (e.g., Cl or other halogen) with a tertiary amine. 4 and R 5 are independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 wherein R is alkyl, aryl, cycloalkyl, heterocycle or any combination thereof; wherein Y represents any leaving group, for example, Cl, Br or I or a sulfonate (e.g., mesyl, tosyl).

[0042] Figure 8 Depicted are schemes of solid support methods and solution methods for preparing standard particles according to some embodiments of the present invention, wherein the antimicrobial unit has one monomer unit (monomer backbone). The circles represent organic or inorganic cores. 1 , Q 2 and Q 3 are independently selected from the group consisting of ethoxy, methoxy, methyl, ethyl, hydrogen, sulfonate, and halide, wherein Q 1 , Q 2 and Q 3 At least one of is a leaving group selected from ethoxy, methoxy, sulfonate (e.g., mesyl, tosyl) and halide. For clarity, the scheme presents the following situation: wherein Q 1 , Q 2 and Q 3 represents the leaving group; Q 4 W is selected from the group consisting of NH2, halide, sulfonate and hydroxyl; and n is an integer between 1 and 16.

[0043] Fig. 9 Depicted are representative protocols for preparing standard particles having (EtO)3Si-CH2-(CH2) by both solid support and solution methods according to some embodiments of the present invention. n -CH2NH2 linker functionalized core particles (represented as circles) with dicinnamyl groups, wherein the antimicrobial unit has one monomer unit (monomer backbone). n is an integer from 1 to 16.

[0044] Fig.10 Representative schemes for preparing standard particles by the solid support method according to some embodiments of the present invention are described, wherein the antimicrobial unit has an oligomeric backbone or a polymeric backbone (more than one monomeric unit). The circle represents the core. The starting material is a core terminated with hydroxyl groups on the surface; Q 101 , Q 102 and Q 103 are independently alkoxy, alkyl or aryl; LG is Cl, Br, I, mesylate, tosylate or triflate; Hal is Cl, Br or I; q, q 1 ,q 2 and q 3 are independently integers between 0 and 16; R 1 and R 2 are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, conjugated alkyl, alkenyl, or any combination thereof; and R 3 is none, hydrogen, an alkyl group, a terpenoid moiety, a cycloalkyl group, an aryl group, a heterocycle, an alkenyl group, an alkynyl group, or any combination thereof.

[0045] Fig.11 Representative schemes for preparing particles with enhanced thermal stability by a solid support method according to some embodiments of the present invention are described, wherein the antimicrobial unit has an oligomeric backbone or a polymeric backbone (more than one monomeric unit). The circle represents the core. The starting material is a core terminated with hydroxyl groups on the surface; Q 101 , Q 102 and Q 103 are each independently alkoxy, alkyl or aryl; LG is Cl, Br, I, mesylate, tosylate or triflate; Hal is Cl, Br or I; q, q 1 ,q 2 and q 3 Each independently is an integer between 0 and 16; R 4 and R 5 are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20alkyl, 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 R 6 Methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C 20 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, a terpenoid moiety, a cycloalkyl, an aryl, a phenyl, a benzyl, a heterocycle, a conjugated alkyl, a 1-alkenyl, a 1-alkynyl, a 2-alkenyl, a 2-alkynyl, or any combination thereof.

[0046] Figure 12A-12C Depicted is the self-polymerization of trialkoxysilane linkers of standard particles according to some embodiments of the present invention. Fig. 12A : Self-polymerization of trialkoxysilane linkers via a solid support method; Fig. 12B : Self-polymerization of trialkoxysilane linkers in solution; and Fig. 12C : Comparison of polymerization of silane groups with simple silanization.

[0047] Figure 13A-13C Depicted is the self-polymerization of trialkoxysilane linkers of particles having enhanced thermal stability according to some embodiments of the present invention. Fig.13A : Self-polymerization of trialkoxysilane linkers via a solid support method; Fig. 13B : Self-polymerization of trialkoxysilane linkers in solution; and Fig. 13C : Comparison of polymerization of silane groups with simple silanization.

[0048] Fig.14 Depicted is a representative scheme for preparing standard particles in a solution process according to some embodiments of the present invention, wherein the antimicrobial unit has more than one monomer unit (e.g., has an oligomeric backbone or a polymeric backbone). The circle represents the core. The starting material is a core terminated with hydroxyl groups on the surface; Q 101 , Q 102 and Q103 are independently alkoxy, alkyl or aryl; LG is Cl, Br, I, mesylate, tosylate or triflate; Hal is Cl, Br or I; q, q 1 ,q 2 and q 3 are independently integers between 0 and 16; R 1 and R 2 are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, conjugated alkyl, alkenyl, or any combination thereof; and R 3 is none, hydrogen, an alkyl group, a terpenoid moiety, a cycloalkyl group, an aryl group, a heterocycle, an alkenyl group, an alkynyl group, or any combination thereof.

[0049] Fig.15 Depicted is a representative scheme for preparing particles with enhanced thermal stability in a solution process, wherein the antimicrobial unit has more than one monomer unit (e.g., has an oligomeric backbone or a polymeric backbone). The circle represents the core. The starting material is a core terminated with hydroxyl groups on the surface; Q 101 , Q 102 and Q 103 are independently alkoxy, alkyl or aryl; LG is Cl, Br, I, mesylate, tosylate or triflate; Hal is Cl, Br or I; q, q 1 ,q 2 and q 3 are independently integers between 0 and 16; R 4 and R 5 are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 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 R 6 Methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C 20Alkyl, 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, a terpenoid moiety, a cycloalkyl, an aryl, a phenyl, a benzyl, a heterocycle, a conjugated alkyl, a 1-alkenyl, a 1-alkynyl, a 2-alkenyl, a 2-alkynyl, or any combination thereof.

[0050] Fig.16 Depicted are schemes for preparing silica-based antimicrobial standard particles comprising dimethylethylammonium as an antimicrobial active group in a solid support process according to some embodiments of the present invention, wherein the antimicrobial unit has more than one monomer unit (e.g., has an oligomeric backbone or a polymeric backbone).

[0051] Fig.17 Depicted are schemes for preparing silica-based antimicrobial standard particles comprising dimethylethylammonium as an antimicrobial active group in a solution process, wherein the antimicrobial unit has more than one monomer unit (e.g., has an oligomeric backbone or a polymeric backbone), according to some embodiments of the present invention.

[0052] Fig.18 Depicted are schemes for preparing silica-based antimicrobial particles with enhanced thermal stability comprising dimethylbenzylammonium as an antimicrobial active group in a solid support process according to some embodiments of the present invention, wherein the antimicrobial unit has more than one monomer unit (e.g., has an oligomeric backbone or a polymeric backbone).

[0053] Fig.19 Depicted are schemes for preparing silica-based antimicrobial particles with enhanced thermal stability comprising dimethylbenzylammonium as an antimicrobial active group in a solution process according to some embodiments of the present invention, wherein the antimicrobial unit has more than one monomer unit (e.g., has an oligomeric backbone or a polymeric backbone).

[0054] It will be understood that, for simplicity and clarity of illustration, the elements shown in the drawings are not necessarily drawn to scale. For example, for clarity, the size of some of the elements may be enlarged relative to other elements. In addition, reference numerals may be repeated in the drawings to indicate corresponding or similar elements where deemed appropriate.

[0055] Detailed description of the invention

[0056] In the following detailed description, many specific details are set forth in order to provide a thorough understanding of the present invention. However, it will be appreciated by those skilled in the art that the present invention can be practiced without these specific details. In other cases, well-known methods, procedures and components are not described in detail in order not to obscure the present invention.

[0057] Antimicrobial particles

[0058] In some embodiments, an antimicrobial particle is provided herein, comprising an organic core or an inorganic core, at least one antimicrobial active unit and at least one polymerizable unit, wherein both the at least one antimicrobial active unit and the at least one polymerizable unit are covalently attached to the core. In one embodiment, the antimicrobial particle comprises more than one identical or different antimicrobial active unit. In one embodiment, the antimicrobial particle comprises more than one identical or different polymerizable unit. In another embodiment, the antimicrobial particle comprises the same or different antimicrobial active units and the same or different polymerizable units in a molar ratio between 10:1 and 1:10. 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 between 2:1 and 1:2. In another embodiment, each antimicrobial active unit comprises one or more antimicrobial groups, and the antimicrobial active unit is chemically (covalently) bound to the core (surface) directly or indirectly (e.g., via a linker and / or other chemical moieties). In another embodiment, each polymerizable unit comprises one or more functional polymerizable groups, and the polymerizable unit is chemically (covalently) bound to the core (surface) directly or indirectly (e.g., via a linker and / or other chemical moieties). In a specific embodiment, the antimicrobial particle comprises an inorganic core, wherein each silicon atom or metal atom in the surface of the inorganic core is functionalized by at least one antimicrobial group or by at least one functional polymerizable group, wherein the molar ratio of silicon atoms or metal atoms functionalized by at least one antimicrobial group in the surface of the inorganic core and silicon atoms or metal atoms functionalized by at least one functional polymerizable unit in the surface of the inorganic core 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 between 2:1 and 1:2. In one embodiment, the functional polymerizable group comprises an acrylate group, an epoxy group, a vinyl group, or an isocyanate group.In one embodiment, the antimicrobial group is a quaternary ammonium, a tertiary amine, or a tertiary ammonium.

[0059] In some non-limiting embodiments, the antimicrobial particles are composed of Figure 1A-Figure 1C Schematically represented. Figure 1A-Figure 1C In it can be seen that the (antimicrobially active and polymerizable) units may be identical or different, as can be inferred from the term ". . . unit 1" or ". . . unit 2". Figure 1A In the formula (A), the number of antimicrobial active units and the number of polymerizable units are the same (6). Figure 1B In , there are more antimicrobially active units than polymerizable units (7 vs. 5, respectively). Figure 1C In , there are more polymerizable units than antimicrobially active units (7 versus 5, respectively).

[0060] In some embodiments, the antimicrobial active unit consists of Figure 2A In one embodiment, the antimicrobial active unit comprises a (polymer / oligomer) backbone covalently linked to one or more monomers (or "monomer units"), wherein the backbone is covalently linked to the inorganic or organic core of the antimicrobial particle of the present invention via a bond or linker (via the concept In another embodiment, the monomer or monomer unit consists of Figure 2B Schematically represented. In other embodiments, each monomer or monomer unit comprises an antimicrobial group.

[0061] In some embodiments, the polymerizable unit consists of Figure 3A In one embodiment, the polymerizable unit comprises a (polymer / oligomer) backbone covalently linked to a monomer (or "monomer unit"), wherein the backbone is covalently linked to the inorganic or organic core of the antimicrobial particle of the present invention via a bond or linker (via the concept In another embodiment, the monomer or monomer unit consists of Figure 3B Represented schematically. In other embodiments, each monomer or monomer unit comprises at least one functional polymerizable group.

[0062] In some embodiments, the number of antimicrobial active units is per square nanometer (nm 2) of the core surface of the particles of 0.01-30. In another embodiment, the number is between 0.01-20 antimicrobial active units per 1 square nanometer of the core surface. In another embodiment, the number is between 0.01-10 antimicrobial active units per 1 square nanometer of the core surface. In another embodiment, the number is between 0.01-15 antimicrobial active units per 1 square nanometer of the core surface. In another embodiment, the number is between 0.01-5 antimicrobial active units per 1 square nanometer of the core surface. Each possibility represents a separate embodiment of the present invention.

[0063] In some embodiments, the number of polymerizable units is per square nanometer (nm 2 ) of the core surface of the particles. In another embodiment, the number is between 0.01-30 polymerizable units per 1 square nanometer of core surface. In another embodiment, the number is between 0.01-20 polymerizable units per 1 square nanometer of core surface. In another embodiment, the number is between 0.01-10 polymerizable units per 1 square nanometer of core surface. In another embodiment, the number is between 0.01-15 polymerizable units per 1 square nanometer of core surface. In another embodiment, the number is between 0.01-5 polymerizable units per 1 square nanometer of core surface. Each possibility represents a separate embodiment of the present invention.

[0064] Antimicrobial activity unit

[0065] A) Branching units and non-branching units

[0066] In some embodiments, the antimicrobial active unit is represented by structure (1):

[0067]

[0068] in

[0069] L1 is the first linker or bond;

[0070] L2 is the second linker;

[0071] L3 is the third linker or bond;

[0072] R1 and R1' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0073] R2 and R2' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0074] R3 and R3' are each independently none, hydrogen, alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; wherein if R3 or R3' is none, the nitrogen is uncharged;

[0075] X1 and X2 are each independently a bond, an alkylene group, an alkenylene group or an alkynylene group;

[0076] n1 is each independently an integer between 0 and 200;

[0077] n2 are each independently an integer between 0 and 200;

[0078] Where n1+n2≥1;

[0079] m is an integer between 1 and 200, and the repeating units are the same or different; and

[0080] concept Represents a covalent bond to an organic or inorganic core.

[0081] In another embodiment, the antimicrobial group is -N(R1)(R2)(R3) + 、-N(R1)(R2) + -、-N(R1')(R2')(R3') + or -N(R1')(R2') + -(all possible groups are covalently linked to X1 or X2).

[0082] In another embodiment, the number of antimicrobial groups per antimicrobial active unit is at least two, for example, n1+n2≥2 and m > 1 ("branching unit"). In another embodiment, the number of antimicrobial groups per antimicrobial active unit is one, for example, n1+n2=1 and m=1 ("non-branching unit").

[0083] In some embodiments, the antimicrobial active unit is represented by structure (2):

[0084]

[0085] in

[0086] L1 is the first linker or bond;

[0087] L2 is the second linker;

[0088] L3 is the third linker or bond;

[0089] R1 and R1' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0090] R2 and R2' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0091] X1 and X2 are each independently a bond, an alkylene group, an alkenylene group or an alkynylene group;

[0092] n1 is each independently an integer between 0 and 200;

[0093] n2 are each independently an integer between 0 and 200;

[0094] Where n1+n2≥1;

[0095] m is an integer between 1 and 200, and the repeating units are the same or different; and

[0096] concept Represents a covalent bond to an organic or inorganic core.

[0097] In another embodiment, the antimicrobial group is -HN(R1)(R2) + 、-HN(R1) + -、-HN(R1')(R2') + or -HN(R1') + -(all possible groups are covalently linked to X1 or X2).

[0098] In another embodiment, the number of antimicrobial groups per antimicrobial active unit is at least two, for example, n1+n2≥2 and m > 1 ("branching unit"). In another embodiment, the number of antimicrobial groups per antimicrobial active unit is one, for example, n1+n2=1 and m=1 ("non-branching unit").

[0099] In some embodiments, the antimicrobial active unit is represented by structure (3):

[0100]

[0101] in

[0102] L1 is the first linker or bond;

[0103] L2 is the second linker;

[0104] L3 is the third linker or bond;

[0105] R1 and R1' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0106] R2 and R2' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0107] X1 and X2 are each independently a bond, an alkylene group, an alkenylene group or an alkynylene group;

[0108] n1 is each independently an integer between 0 and 200;

[0109] n2 are each independently an integer between 0 and 200;

[0110] Where n1+n2≥1;

[0111] m is an integer between 1 and 200, and the repeating units are the same or different; and

[0112] concept Represents a covalent bond to an organic or inorganic core.

[0113] In another embodiment, the antimicrobial group is -N(R1)(R2), -N(R1)-, -N(R1')(R2'), or -N(R1')- (all possible groups are covalently linked to X1 or X2).

[0114] In another embodiment, the number of antimicrobial groups per antimicrobial active unit is at least two, for example, n1+n2≥2 and m > 1 ("branching unit"). In another embodiment, the number of antimicrobial groups per antimicrobial active unit is one, for example, n1+n2=1 and m=1 ("non-branching unit").

[0115] In another embodiment, the antimicrobial active units of structures (1) to (3) comprise one monomer unit per antimicrobial active unit. In another embodiment, the antimicrobial active units of structures (1) to (3) comprise more than one antimicrobial group per antimicrobial active unit.

[0116] B) Non-branching unit

[0117] In some embodiments, the antimicrobial active unit is represented by structure (4):

[0118]

[0119] in

[0120] L1 is the first linker or bond;

[0121] L3 is the third linker or bond;

[0122] R1 is alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0123] R2 is alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0124] R3 is none, hydrogen, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; wherein if R3 or R3' is none, the nitrogen is uncharged;

[0125] X is a bond, alkyl, alkenyl or alkynyl;

[0126] X' is nothing or hydrogen; and

[0127] Wherein if L1 and X are a bond, then the nitrogen is part of an organic or inorganic core;

[0128] wherein at least one of R1, R2, and R3 is hydrophobic; and

[0129] concept Represents a covalent bond to an organic or inorganic core.

[0130] In another embodiment, the antimicrobial group is {N(R1)(R2)(R3)} + (covalently linked to X).

[0131] In some embodiments, the antimicrobial active unit is represented by structure (5):

[0132]

[0133] in

[0134] L1 is the first linker or bond;

[0135] L3 is the third linker or bond;

[0136] R1 is alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0137] R2 is alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0138] X is a bond, alkyl, alkenyl or alkynyl;

[0139] X' is nothing or hydrogen; and

[0140] Wherein if L1 and X are a bond, then the nitrogen is a component of an organic or inorganic core;

[0141] wherein at least one of R1 and R2 is hydrophobic; and

[0142] concept Represents a covalent bond to an organic or inorganic core.

[0143] In another embodiment, the antimicrobial group is {HN(R1)(R2)} + (covalently linked to X). In some embodiments, the antimicrobial active unit is represented by structure (6):

[0144]

[0145] in

[0146] L1 is the first linker or bond;

[0147] L3 is the third linker or bond;

[0148] R1 is alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0149] R2 is alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0150] X is a bond, alkyl, alkenyl or alkynyl;

[0151] X' is nothing or hydrogen; and

[0152] Wherein if L1 and X are a bond, then the nitrogen is a component of an organic or inorganic core;

[0153] wherein at least one of R1 and R2 is hydrophobic; and

[0154] concept Represents a covalent bond to an organic or inorganic core.

[0155] In another embodiment, the antimicrobial group is {N(R1)(R2)} (covalently linked to X). Specific examples of the antimicrobial active units of the present invention include:

[0156]

[0157]

[0158] Where n = 1-200; and the concept represents 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 polyhedral oligomeric silsesquioxane (POSS).

[0159] In some embodiments, the term "antimicrobial group" and the term "monomeric antimicrobial group" refer to the same group and include a protonated tertiary amine, a tertiary amine, or a quaternary ammonium, such as represented by the following formula:

[0160]

[0161] in:

[0162] R1 is alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0163] R2 is alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof;

[0164] R3 is none, hydrogen, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof; wherein if R3 or R3' is none, the nitrogen is uncharged.

[0165] In another embodiment, at least one of R1, R2 or R3 is hydrophobic.

[0166] In another embodiment, the number of antimicrobial groups per antimicrobial active unit is at least two, for example, n1+n2≥2 and m > 1. In another embodiment, the number of antimicrobial groups per antimicrobial active unit is one, for example, n1+n2=1 and m=1.

[0167] In another embodiment, the antimicrobial active unit of structures (4) to (6) comprises one monomer unit. In another embodiment, the antimicrobial active unit of structures (1) to (3) comprises one or more than one antimicrobial group.

[0168] In another embodiment, the antimicrobial active units of structures (1) to (6) are covalently bound to an inorganic core. In another embodiment, the antimicrobial active units of structures (1) to (6) are covalently bound to an organic core. In another embodiment, the organic core is a polymer organic core. In another embodiment, the core is inert. In one embodiment, the antimicrobial active units of the present invention represented by structures (1) to (3) comprise - + 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, 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, heterocycle, 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 alkenyls. In another embodiment, R1 and / or R1', R2 and / or R2' and R3 and / or R3' are independently alkynyls. In another embodiment, R3 is nothing. In another embodiment, R3 and / or R3' are hydrogen. In another embodiment, at least one of R1 and / or R1', R2 and / or R2' and R3 and / or R3' is a hydrophobic alkyl, terpenoid, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl or any combination thereof. Each represents a separate embodiment of the present invention.

[0169] 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.

[0170] In one embodiment, at least one of R1, R2 and R3 and / or at least one of R1', R2' and R3' of structure (1) is hydrophobic. In one embodiment, at least one of R1 and R2 and / or at least one of R1' and R2' of structures (2) and (3) is hydrophobic.

[0171] The term "hydrophobic" refers to an alkyl, alkenyl or alkynyl group having at least four carbons, or the term "hydrophobic" refers to a terpenoid, refers to a cycloalkyl, aryl or heterocyclic group having at least six carbons. Each possibility represents a separate embodiment of the present invention.

[0172] In one embodiment, at least one of R1, R2 and R3 and / or at least one of R1', R2' and R3' of structure (1) is C4-C 24 Alkyl, C4-C 24 Alkenyl, C4-C 24 In one embodiment, at least one of R1 and R2 and / or at least one of R1' and R2' of structures (2) and (3) is C4-C 24 Alkyl, C4-C 24 Alkenyl, C4-C 24 Alkynyl or terpenoid. Each possibility represents a separate embodiment of the present invention.

[0173] In one embodiment, at least one of R1, R2 and R3 and / or at least one of R1', R2' and R3' of 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' of 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.

[0174] In one embodiment, R1 and / or R1' of structures (1) to (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 none, 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 none, 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-C 24 Alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, conjugated C1-C 24 Alkyl, C1-C 24 Alkenyl, C1-C 24 alkynyl or any combination thereof, and R1 and / or R1' is terpenoid.

[0175] In one embodiment, the particle of the present invention comprises an antimicrobially active unit and an inert core, wherein the antimicrobially active unit and the core are indirectly linked.

[0176] In some embodiments, L1, L2 or L3 are each independently the same or different linkers. In some embodiments, L1, L2 and L3 are connected to each other in any possible way. In some embodiments, L3 is nothing (or a key), and L1 or L2 is covalently connected to the core. In another embodiment, L3 is covalently connected to the core, and L1 or L2 is connected to L3. In another embodiment, L1 is connected to X, X' and L3 or the core. In another embodiment, "linker" includes any possible chemical part that can connect at least two other chemical parts adjacent to such a linker. In another embodiment, the monomer unit of the antimicrobial active unit includes the first linker and / or the second linker (L1 or L2) and an antimicrobial group. In another embodiment, L1 and / or L2 are the skeletons of the antimicrobial active unit. In another embodiment, the monomer unit of the antimicrobial active unit includes the first linker and / or the second linker (L1 or L2) and an antimicrobial group. In another embodiment, L1 and / or L2 are the backbone of the antimicrobial active unit (they are, for example, alkylene, polypeptide or oligosiloxane (-Si(OH)2-O- or -Si(CH3)2-O-) moieties).

[0177] In some embodiments, the linker comprises a functional group. In another embodiment, the linker comprises two (same or different) functional groups. In another embodiment, the functional group comprises a phosphate, a phosphonate, a siloxane, a silane, an ether, an 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.

[0178] In another embodiment, L1 or L2 is a C1 to C18 alkylene, alkenylene, alkynylene or aryl substituted with at least one carboxyl moiety, wherein the carboxyl terminus is attached to the core. The linker may be derived from a C1 to C18 alkylene substituted with at least one carboxyl moiety and having an amino terminus modified 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'),- +In another embodiment, L1 or L2 is a C1 to C18 alkylene group substituted with at least one amine or amide moiety.

[0179] In another embodiment, L1, L2, L3 or any combination thereof is C1 to C18 alkylene, alkenylene, alkynylene or aryl. The linker can be derived from a dihaloalkylene by replacing the halogen moiety with a functional group bound to the core and replacing the halogen moiety to obtain [- + 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) to (6))] and functionalized at each end with a core and an antimicrobial group, respectively.

[0180] In another embodiment, L1, L2, L3 or any combination thereof is an aromatic group derived from the non-limiting examples of 4,4-bisphenol, dibenzoic acid, dibenzoic acid halide, dibenzoic acid sulfonate, terephthalic acid, terephthalic acid halide and terephthalic acid sulfonate. The linker is functionalized by the core and the antimicrobial group through its functional group (e.g., hydroxyl, carboxyl or sulfonate), respectively. In another embodiment, the linker is directly attached to the core at one end or indirectly attached to the core via a third linker (L3) and is modified 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'),- + NH(R1′)-, -N(R1′)(R2′) or -N(R1′)- (as defined in Structures (1) to (6))].

[0181] In another embodiment, L1, L2, L3 or any combination thereof is a siloxane group or a silane group derived from 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 by the core and the antimicrobial group respectively through its functional group (e.g., hydroxyl, siloxane, carboxyl, amide or sulfonate). In another embodiment, the linker is directly attached to the core at one end or indirectly attached to the core via a third linker (L3) and is modified 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'),- + NH(R1′)-, -N(R1′)(R2′) or -N(R1′)- (as defined in Structures (1) to (6))].

[0182] In one embodiment, the antimicrobial groups of the present invention can be selected from: (a) a tertiary amine (e.g., R3 and / or R3' is absent) or a tertiary ammonium (e.g., R3 and / or R3' is hydrogen) comprising at least one terpenoid moiety; (b) a quaternary ammonium group comprising at least one terpenoid moiety; (c) a quaternary ammonium group comprising at least one alkyl group having from 4 to 24 carbon atoms; and (d) a tertiary amine (e.g., R3 and / or R3' is absent) or a tertiary ammonium (e.g., R3 and / or R3' is hydrogen) comprising at least one alkyl group having from 4 to 24 carbon atoms. Each possibility represents a separate embodiment of the present invention.

[0183] The linker is functionalized by the core and the antimicrobial active unit, respectively, through its functional groups (e.g., hydroxyl, siloxane, carboxyl, amide or sulfonate). In another embodiment, the linker is directly attached to the core at one end or indirectly attached to the core via a third linker (L3) and is modified 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'),- + NH(R1′)-, -N(R1′)(R2′) or -N(R1′)- (as defined in Structures (1) to (6))].

[0184] In another embodiment, the monomer units within the antimicrobial active units of the present invention (such as in e.g. Figure 2A-2B and described in Formula 1-6) are represented by the structure of Formula IA:

[0185]

[0186] in

[0187] R1 and R2 are independently linear or branched alkyl, terpenoid, cycloalkyl, aryl, heteroaryl, alkenyl, alkynyl or any combination thereof; and

[0188] R3 is none, linear or branched alkyl, terpenoid, cycloalkyl, aryl, heteroaryl, alkenyl, alkynyl, or any combination thereof; wherein if R3 is none, the nitrogen is uncharged.

[0189] q is an integer between 0 and 16;

[0190] The monomer unit is chemically bonded to the surface of the inorganic core directly or via a third linker (L3).

[0191] In another embodiment, the monomer units within the antimicrobial active units of the present invention (such as in e.g. Figure 2A-2B and described in Formula 1-6) are represented by the structure of Formula IB:

[0192]

[0193] in

[0194] R1 and R2 are independently linear or branched alkyl, terpenoid, cycloalkyl, aryl, heteroaryl, alkenyl, alkynyl or any combination thereof; and

[0195] R3 is none, linear or branched alkyl, terpenoid, cycloalkyl, aryl, heteroaryl, alkenyl, alkynyl, or any combination thereof; wherein if R3 is none, the nitrogen is uncharged.

[0196] q and q 1 are independently integers between 0 and 16.

[0197] The monomer unit is chemically bonded to the surface of the inorganic core directly or via a third linker (L3).

[0198] In another embodiment, a linker molecule that can be used in the process of preparing the antimicrobial particles of the present invention is represented by the structure of Formula IC:

[0199]

[0200] in

[0201] Q 201 , Q 202 and Q 203 are independently selected from the group consisting of alkoxy, methyl, ethyl, hydrogen, sulfonate, and halide, wherein Q 201 , Q 202 and Q 203 At least one of is selected from ethoxy, methoxy, sulfonate (e.g., mesyl, tosyl), and halide; and

[0202] q is an integer between 0 and 16;

[0203] The linker molecule is capable of chemically bonding to the surface of the inorganic core via the silicon atom; and

[0204] The antimicrobial groups are introduced by functionalizing primary amines to obtain antimicrobially active tertiary amines or quaternary ammonium groups comprising at least one terpenoid group as described above.

[0205] In another embodiment, a linker molecule that can be used in the process of preparing the antimicrobial particles of the present invention is represented by the structure of Formula ID:

[0206]

[0207] in

[0208] Q 201 , Q 202 and Q 203 are independently selected from the group consisting of alkoxy, methyl, ethyl, hydrogen, sulfonate, and halide, wherein Q201 , Q 202 and Q 203 At least one of the following is selected from ethoxy, methoxy, sulfonate (e.g., mesyl, tosyl), and halide;

[0209] W is selected from the group consisting of NH2, halide, sulfonate and hydroxyl; and

[0210] q is an integer between 0 and 16;

[0211] The linker is capable of chemically bonding to the surface of the inorganic core through silicon atoms; and

[0212] The antimicrobial group is introduced by substituting the group W with an antimicrobial group, or converting the group W into an antimicrobial group.

[0213] An antimicrobial group comprising a long alkyl group.

[0214] 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) to (6))] is a quaternary ammonium group, a tertiary amine or a tertiary ammonium, and each nitrogen atom of the amine / ammonium group has at least one bond to X1 or X2, and at least one bond to an alkyl group (R1 and / or R1') having from 4 to 24 carbon atoms. In another embodiment, each nitrogen atom of the amine / ammonium group has one bond to the core, and one bond to an alkyl group (R1 and / or R1') having from 4 to 24 carbon atoms.

[0215] In some embodiments, the nitrogen atom of each quaternary 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 from 4 to 24 carbon atoms.

[0216] In some embodiments, the antimicrobial groups of formula (1) to (6) are selected from: (a) tertiary amines (R3 and / or R3' are absent) or tertiary ammoniums (R3 and / or R3' are H), wherein each nitrogen atom of the tertiary amine / tertiary ammonium has at least one bond to X1 or X2 and one bond to an alkyl group having from 4 to 24 carbon atoms; (b) tertiary amines (R3 and / or R3' are absent) or tertiary ammoniums (R3 and / or R3' are H) or salts of said tertiary amines, wherein each nitrogen atom of the tertiary amine / tertiary ammonium has one bond to X1 or X2 and two bonds to an alkyl group having from 4 to 24 carbon atoms, which may be the same or different from each other; (c) quaternary ammonium groups, wherein each nitrogen atom of the quaternary ammonium group has at least one bond to X1 or X2 and one or two bonds to an alkyl group having from 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.

[0217] The term "quaternary ammonium group" refers to an atom group consisting of a nitrogen atom and four substituents (different from hydrogen) attached thereto. In another embodiment, a "quaternary ammonium group" refers to an atom group consisting of a nitrogen atom and four groups, wherein each group is attached to nitrogen by a carbon atom. The term "long alkyl group" or chain refers to an alkyl group or chain that is substituted on the nitrogen atom of the quaternary ammonium group and has a carbon atom between 4 and 24. In some embodiments, an alkyl group is an alkyl group with 4 to 18 carbon atoms. In some embodiments, an alkyl group is an alkyl group with 4 to 8 carbon atoms. In some embodiments, an alkyl group is an alkyl group with 4 to 10 carbon atoms. In other embodiments, an alkyl group is an alkyl group with 6, 7 or 8 carbon atoms, wherein each possibility represents a single embodiment of the present invention.

[0218] C) Heat stable antimicrobial unit

[0219] In one embodiment, the antimicrobial active unit is represented by structure (I):

[0220]

[0221] in

[0222] The core is an organic polymer or an inorganic material;

[0223] L4 is the first linker or bond;

[0224] L5 is the second connector;

[0225] L6 is a third linker or bond;

[0226] Z1 is

[0227] Z2 is

[0228] R4 and R4' are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 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;

[0229] R5 and R5' are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 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;

[0230] R6 and R6' are each independently absent, methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C 20 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, a terpenoid moiety, a cycloalkyl, an aryl, a phenyl, a benzyl, a heterocycle, a conjugated alkyl, a 1-alkenyl, a 1-alkynyl, a 2-alkenyl, a 2-alkynyl, or any combination thereof;

[0231] R7 and R7' are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20alkyl, 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;

[0232] R8 and R8' are each independently H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl or any combination thereof;

[0233] R9 and R9' are each independently H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl or any combination thereof;

[0234] R 10 and R 10 ' are each independently H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl or any combination thereof;

[0235] R 11 and R 11 ' are each independently H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl or any combination thereof;

[0236] X3 and X4 are each independently a bond, an alkylene group, an arylene group, an alkenylene group, an alkynylene group, or any combination thereof;

[0237] 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;

[0238] R is alkyl, aryl, cycloalkyl, heterocycle or any combination thereof;

[0239] n1 is each independently an integer between 0 and 200;

[0240] n2 are each independently an integer between 0 and 200;

[0241] Where n1+n2≥1;

[0242] m is an integer between 1 and 200, and the repeating units are the same or different; and

[0243] concept Represents a covalent bond to an organic or inorganic core.

[0244] In another embodiment, the antimicrobial group is Z1 or Z2 (both possible groups are covalently linked to X3 or X4).

[0245] In another embodiment, with the proviso that Z1 or Z2 comprises an ammonium nitrogen (not pyridinium) - in each of the antimicrobially active units, only one moiety on the ammonium can have a beta hydrogen available for Hofmann elimination. In another embodiment, with the proviso that Z1 or Z2 comprises an ammonium nitrogen (not pyridinium) - in each of the antimicrobially active units, two moieties on the ammonium can have a beta hydrogen available for Hofmann elimination. In another embodiment, the beta hydrogens available for Hofmann elimination are those present on the beta (compared to the ammonium nitrogen) aliphatic carbons and can be eliminated to release an olefin and a tertiary amine.

[0246] In another embodiment, the antimicrobial active unit is represented by the structure (IE):

[0247]

[0248]

[0249] in

[0250] The core is an organic polymer or an inorganic material;

[0251] L4 is the first linker or bond;

[0252] L6 is a third linker or bond;

[0253] Z1 is

[0254] R4 is methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 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;

[0255] R5 is methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20alkyl, 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;

[0256] R6 is methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C 20 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, a terpenoid moiety, a cycloalkyl, an aryl, a phenyl, a benzyl, a heterocycle, a conjugated alkyl, a 1-alkenyl, a 1-alkynyl, a 2-alkenyl, a 2-alkynyl, or any combination thereof;

[0257] R7 is methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 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;

[0258] R8 is H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl or any combination thereof;

[0259] R9 is H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl or any combination thereof;

[0260] R 10 is H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl or any combination thereof;

[0261] R 11is H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl or any combination thereof;

[0262] X3 is a bond, alkylene, arylene, alkenylene, alkynylene or any combination thereof;

[0263] X5 is 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;

[0264] R is alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof; and

[0265] concept Represents a covalent bond to an organic or inorganic core.

[0266] In another embodiment, the antimicrobial group is Z1 (covalently linked to X3).

[0267] In another embodiment, with the proviso that Z1 comprises an ammonium nitrogen (not pyridinium) - in each of the antimicrobially active units, only one moiety on the ammonium can have a beta hydrogen available for Hofmann elimination. In another embodiment, with the proviso that Z1 or Z2 comprises an ammonium nitrogen (not pyridinium) - in each of the antimicrobially active units, both moieties on the ammonium can have a beta hydrogen available for Hofmann elimination.

[0268] In another embodiment, the antimicrobial active unit is represented by structure (II):

[0269]

[0270] in

[0271] The core is an organic polymer or an inorganic material;

[0272] L4 is the first linker or bond;

[0273] L5 is the second connector;

[0274] L6 is a third linker or bond;

[0275] R4 and R4' are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20alkyl, 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;

[0276] R5 and R5' are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 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;

[0277] R6 and R6' are each independently methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C 20 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, a terpenoid moiety, a cycloalkyl, an aryl, a phenyl, a benzyl, a heterocycle, a conjugated alkyl, a 1-alkenyl, a 1-alkynyl, a 2-alkenyl, a 2-alkynyl, or any combination thereof;

[0278] R7 and R7' are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20alkyl, 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;

[0279] R8 and R8' are each independently H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl or any combination thereof;

[0280] R9 and R9' are each independently H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl or any combination thereof;

[0281] R 10 and R 10 ' are each independently H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl or any combination thereof;

[0282] R 11 and R 11 ' are each independently H, alkyl, terpenoid moiety, cycloalkyl, aryl, heterocycle, conjugated alkyl, alkenyl, alkynyl or any combination thereof;

[0283] X3 and X4 are each independently a bond, an alkylene group, an arylene group, an alkenylene group, an alkynylene group, or any combination thereof;

[0284] R is alkyl, aryl, cycloalkyl, heterocycle or any combination thereof;

[0285] n1 is each independently an integer between 0 and 200;

[0286] n2 are each independently an integer between 0 and 200;

[0287] n3 and n4 are each independently 0 or 1;

[0288] where n1+n2≥1; and

[0289] m is an integer between 1 and 200, and the repeating units are the same or different; and

[0290] concept Represents a covalent bond to an organic or inorganic core.

[0291] In another embodiment, the antimicrobial group is -N(R4)(R5)(R6) +or -N(R4')(R5')(R6') + (All possible groups are covalently linked to {(CH2)n3} or {(CH2)n4}).

[0292] In another embodiment, in each of the antimicrobially active units, only one moiety on the ammonium may have a beta hydrogen available for Hofmann elimination.

[0293] In another embodiment, the antimicrobial active unit is represented by structure (III):

[0294]

[0295] in

[0296] The core is an organic polymer or an inorganic material;

[0297] L4 is the first linker or bond;

[0298] L5 is the second connector;

[0299] L6 is a third linker or bond;

[0300] X3 and X4 are each independently a bond, an alkylene group, an arylene group, an alkenylene group, an alkynylene group, or any combination thereof;

[0301] n1 is each independently an integer between 0 and 200;

[0302] n2 are each independently an integer between 0 and 200;

[0303] Where n1+n2≥1;

[0304] m is an integer between 1 and 200, and the repeating units are the same or different; and

[0305] concept Represents a covalent bond to an organic or inorganic core.

[0306] In another embodiment, the antimicrobial group is -N(CH3)3 + (covalently bound to {CH2}).

[0307] In another embodiment, the antimicrobial active unit is represented by structure (IV):

[0308]

[0309] in

[0310] The core is an organic polymer or an inorganic material;

[0311] L4 is the first linker or bond;

[0312] L5 is the second connector;

[0313] L6 is a third linker or bond;

[0314] X3 and X4 are each independently a bond, an alkylene group, an arylene group, an alkenylene group, an alkynylene group, or any combination thereof;

[0315] n1 is each independently an integer between 0 and 200;

[0316] n2 are each independently an integer between 0 and 200;

[0317] Where n1+n2≥1;

[0318] m is an integer between 1 and 200, and the repeating units are the same or different; and

[0319] concept Represents a covalent bond to an organic or inorganic core.

[0320] In another embodiment, the antimicrobial group is -N(CH3)3 + (covalently linked to {C6H4}).

[0321] In another embodiment, the antimicrobial active unit is represented by structure (V):

[0322]

[0323] in

[0324] The core is an organic polymer or an inorganic material;

[0325] L4 is the first linker or bond;

[0326] L5 is the second connector;

[0327] L6 is a third linker or bond;

[0328] X3 and X4 are each independently a bond, an alkylene group, an arylene group, an alkenylene group, an alkynylene group, or any combination thereof;

[0329] n1 is each independently an integer between 0 and 200;

[0330] n2 are each independently an integer between 0 and 200;

[0331] Where n1+n2≥1;

[0332] m is an integer between 1 and 200, and the repeating units are the same or different; and

[0333] concept Represents a covalent bond to an organic or inorganic core.

[0334] In another embodiment, the antimicrobial group is -N(CH3)3 + (covalently linked to {C6H4}).

[0335] In another embodiment, the antimicrobial active unit is represented by structure (VI):

[0336]

[0337] in

[0338] The core is an organic polymer or an inorganic material;

[0339] L4 is the first linker or bond;

[0340] L5 is the second connector;

[0341] L6 is a third linker or bond;

[0342] X3 and X4 are each independently a bond, an alkylene group, an arylene group, an alkenylene group, an alkynylene group, or any combination thereof;

[0343] n1 is each independently an integer between 0 and 200;

[0344] n2 are each independently an integer between 0 and 200;

[0345] Where n1+n2≥1;

[0346] m is an integer between 1 and 200, and the repeating units are the same or different; and

[0347] concept Represents a covalent bond to an organic or inorganic core.

[0348] In another embodiment, the antimicrobial group is -N(CH3)3 + (covalently bound to {CH2}).

[0349] In another embodiment, the antimicrobial active unit is represented by structure (VII):

[0350]

[0351] in

[0352] The core is an organic polymer or an inorganic material;

[0353] L4 is the first linker or bond;

[0354] L5 is the second connector;

[0355] L6 is a third linker or bond;

[0356] X3 and X4 are each independently a bond, an alkylene group, an arylene group, an alkenylene group, an alkynylene group, or any combination thereof;

[0357] n1 is each independently an integer between 0 and 200;

[0358] n2 are each independently an integer between 0 and 200;

[0359] Where n1+n2≥1;

[0360] m is an integer between 1 and 200, and the repeating units are the same or different; and

[0361] concept Represents a covalent bond to an organic or inorganic core.

[0362] In another embodiment, the antimicrobial group is (covalently linked to X3 or X4).

[0363] In some embodiments, the antimicrobial particles comprising antimicrobial active units of structures (I), (IE), and (II)-(VII) have high thermal stability. Without being bound by any mechanism or theory, this suggests that the high stability results from a lack of available beta (β) hydrogens on the ammonium or a low number of available beta (β) hydrogens, thereby reducing the possibility of Hofmann elimination, which in turn leads to reduced thermal stability.

[0364] In some embodiments, the term "antimicrobial group" and the term "monomeric antimicrobial group" refer to the same group and comprise quaternary ammonium and / or pyridinium, such as represented by the following formula:

[0365]

[0366] in:

[0367] R4-R 11 and R4'-R 11 ' is as described above.

[0368] In another embodiment, the number of antimicrobial groups per antimicrobial active unit is at least two, for example, n1+n2≥2 and m > 1. In another embodiment, the number of antimicrobial groups per antimicrobial active unit is one, for example, n1+n2=1 and m=1.

[0369] In another embodiment, the antimicrobial active units of structure (IE) comprise one monomer unit per antimicrobial active unit. In another embodiment, the antimicrobial active units of structure (I) and structures (II) to (VII) comprise one or more antimicrobial groups per antimicrobial active unit.

[0370] In another embodiment, the antimicrobial active units of Structure (I), Structure (IE), and Structure (II)-Structure (VII) have an inorganic core. In another embodiment, the antimicrobial active units of Structure (I), Structure (IE), and Structure (II)-Structure (VII) are connected to an organic core. In another embodiment, the organic core is a polymer organic core. In another embodiment, the core is inert.

[0371] In one embodiment, Z1 is Among them, X5 and R4-R 11 Each possibility represents a separate embodiment of the present invention.

[0372] In one embodiment, Z2 is Among them, X6 and R 4’ -R 11’ Each possibility represents a separate embodiment of the present invention.

[0373] In one embodiment, R4 and / or R4', R5 and / or R5' and R7 and / or R7' are the same or different and 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, -CHCF3, -CHNO2, 1-alkenyl, 1-alkynyl, 2-alkenyl, 2-alkynyl, or any combination thereof, wherein R is described below. Each possibility represents a separate embodiment of the present invention.

[0374] In one embodiment, R6 and R6' are each independently absent, 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, -CHCF3, -CHNO2, a terpenoid moiety, a cycloalkyl, an aryl, a phenyl, a benzyl, a heterocycle, a conjugated alkyl, a 1-alkenyl, a 1-alkynyl, a 2-alkenyl, a 2-alkynyl, or any combination thereof. Each possibility represents a separate embodiment of the present invention.

[0375] In one embodiment, R8 and / or R8', R9 and / or R9', 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.

[0376] In one embodiment, X3 and / or X4 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.

[0377] 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.

[0378] In one embodiment, R is alkyl, aryl, cycloalkyl, heterocycle, or any combination thereof. Each possibility represents a separate embodiment of the present invention.

[0379] 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 ' are the same. In another embodiment, R11 and R 11 In 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 ' are different. In another embodiment, R 11 and R 11 In another embodiment, X3 and X4 are different. In another embodiment, X5 and X6 are different.

[0380] 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.

[0381] In another embodiment, R6, R8-R 11 and at least one of X5 and / or R6', R8'-R 11 At least one of X' and X6 is a terpenoid. Each possibility represents a separate embodiment of the present invention.

[0382] In one embodiment, n3 and n4 of structure (II) are each independently 0 or 1. Each possibility represents a separate embodiment of the present invention.

[0383] In some embodiments, L4, L5 or L6 are each independently the same or different connectors. In some embodiments, L4, L5 and L6 are connected to each other in any possible way. In some embodiments, L6 is nothing (or a key), and L4 or L5 is covalently connected to the core. In another embodiment, L6 is covalently connected to the core, and L4 or L5 is connected to L6. In another embodiment, L4 is connected to X3, L5 and L6 or the core. In another embodiment, "connector" includes any possible chemical part that can connect at least two other chemical parts adjacent to such a connector. In another embodiment, the monomer unit of the antimicrobial active unit includes the first connector and / or the second connector (L4 or L5) and an antimicrobial group. In another embodiment, L4 and / or L5 are the skeletons of the antimicrobial active units (they are, for example, alkylene, polypeptide or oligosiloxane (-Si (OH) 2-O- or-Si (CH 3) 2-O-) parts). In some embodiments, the connector includes a functional group. In another embodiment, the linker comprises two (same or different) functional groups. In another embodiment, the functional groups include phosphates, phosphonates, siloxanes, silanes, ethers, acetals, hydroxyls, amides, amines, anhydrides, esters, ketones, or one or more aromatic rings functionalized with any of the foregoing moieties. Each possibility represents a separate embodiment of the present invention.

[0384] In another embodiment, L4, L5, L6, X3, X4, X5, X6 or any combination thereof is a C1 to C18 alkylene, alkenylene, alkynylene or aryl substituted with at least one carboxyl moiety, wherein the carboxyl terminus is attached to the core. They may be derived from a C1 to C18 alkylene substituted with at least one carboxyl moiety and having an amino terminus modified to an antimicrobial group [- + N(R4)(R5)(R6),- + N(R4')(R5')(R6'), [as 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 between 2 and 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, X3, X4, X5, X6 or any combination thereof is substituted by at least one amine, amide or pyridinium Partially substituted C1 or C18 alkylene.

[0385] In another embodiment, L4, L5, L6, X3, X4, X5, X6 or any combination thereof is C1-C18 alkylene, alkenylene, alkynylene, arylene or aryl. The linker can be derived from a dihaloalkylene or dihaloarylene group by replacing the halogen moiety with a functional group bound to the core and replacing the halogen moiety to obtain - + N(R4)(R5)(R6) or - + N(R4')(R5')(R6') (which are defined in Structures (I) to (II)) and functionalized at each end with a core and an antimicrobial group, respectively.

[0386] In another embodiment, L4, L5, L6, X3, X4, X5, X6 or any combination thereof is an aromatic group derived from the non-limiting examples of 4,4-bisphenol, dibenzoic acid, dibenzoic acid halide, dibenzoic acid sulfonate, terephthalic acid, terephthalic acid halide and terephthalic acid sulfonate. The linker is functionalized by the core and the antimicrobial group through its functional group (e.g., hydroxyl, carboxyl or sulfonate), respectively. In another embodiment, the linker is directly attached to the core at one end or indirectly attached to the core via a third linker (L6) and is modified to an antimicrobial group [- + N(R4)(R5)(R6),- + N(R4')(R5')(R6'), defined in Structure (I) and Structure (IE)].

[0387] In another embodiment, L4, L5, L6, X3, X4, X5, X6 or any combination thereof is a siloxane group or a silane group derived from 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 by the core and the antimicrobial group respectively through its functional group (e.g., hydroxyl, siloxane, carboxyl, amide or sulfonate). In another embodiment, the linker is directly attached to the core at one end or indirectly attached to the core via a third linker (L6) and is modified to an antimicrobial group [- + N(R4)(R5)(R6),- + N(R4')(R5')(R6'), defined in Structure (I) and Structure (IE)].

[0388] The linker is functionalized by the core and the antimicrobial group, respectively, through its functional groups (e.g., hydroxyl, siloxane, carboxyl, amide, or sulfonate). In another embodiment, the linker is directly attached to the core at one end or indirectly attached to the core via a third linker (L6), and is modified to an antimicrobial group [- + N(R4)(R5)(R6),- + N(R4')(R5')(R6'), defined in Structure (I) and Structure (IE)].

[0389] In another embodiment, the monomer units within the antimicrobial active units of the present invention (such as in e.g. Figure 2A-2B and Formula IE and Formula I-Formula VII) are represented by the structure of Formula IF1 or Formula IF2:

[0390]

[0391] in

[0392] R4 and R5 are independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 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;

[0393] R6 is methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C 20 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, a terpenoid moiety, a cycloalkyl, an aryl, a phenyl, a benzyl, a heterocycle, a conjugated alkyl, a 1-alkenyl, a 1-alkynyl, a 2-alkenyl, a 2-alkynyl, or any combination thereof;

[0394] R is alkyl, aryl, cycloalkyl, heterocycle or any combination thereof;

[0395] q is an integer between 0 and 16; and

[0396] The monomer unit is chemically bonded to the surface of the inorganic core directly or via a third linker (L6).

[0397] In another embodiment, the monomer units within the antimicrobial active units of the present invention (such as in e.g. Figure 2A-2B and Formula IE and Formula I-Formula VII) are represented by the structure of Formula IG1 or Formula IG2:

[0398]

[0399] in

[0400] R4-R6 are as described above;

[0401] q and q 1 are independently integers between 0 and 16; and

[0402] The monomer unit is chemically bonded to the surface of the inorganic core directly or via a third linker (L6).

[0403] In another embodiment, the linker molecule that can be used in the process of preparing the antimicrobial particles of the present invention is represented by the structure of Formula IH1 or Formula IH2:

[0404]

[0405] in

[0406] Q 201 , Q 202 and Q 203 are independently selected from the group consisting of alkoxy, methyl, ethyl, hydrogen, sulfonate, and halide, wherein Q 201 , Q 202 and Q 203 At least one of the following is selected from ethoxy, methoxy, sulfonate (e.g., mesyl, tosyl), and halide;

[0407] q is an integer between 0 and 16;

[0408] The linker molecule is capable of chemically bonding to the surface of the inorganic core via the silicon atom; and

[0409] The antimicrobial groups are introduced by functionalizing primary amines to obtain antimicrobially active quaternary ammonium groups as described above.

[0410] In another embodiment, a linker molecule that can be used in the process of preparing the antimicrobial particles of the present invention is represented by the structure of Formula IJ:

[0411]

[0412] in

[0413] Q 201 , Q 202 and Q 203 are independently selected from the group consisting of alkoxy, methyl, ethyl, hydrogen, sulfonate, and halide, wherein Q 201 , Q 202 and Q 203 At least one of the following is selected from ethoxy, methoxy, sulfonate (e.g., mesyl, tosyl), and halide;

[0414] W1 is selected from the group consisting of arylene-NH2, benzylidene-NH2, halide, sulfonate and hydroxyl;

[0415] q is an integer between 0 and 16;

[0416] The linker is capable of chemically bonding to the surface of the inorganic core through silicon atoms; and

[0417] The antimicrobial group is introduced by substituting the group W with the antimicrobial group or converting the group W into an antimicrobial group.

[0418] An antimicrobial group comprising a long alkyl group.

[0419] In one embodiment, the antimicrobial group of the present invention comprises an alkyl group having from 4 to 24 carbon atoms as the antimicrobial group [ R8-R defined in Structure (I) and Structure (IE) 11 and / or R8'-R 11 '.

[0420] The term "quaternary ammonium group" refers to an atom group consisting of a nitrogen atom and four substituents (different from hydrogen) attached thereto. In another embodiment, a "quaternary ammonium group" refers to an atom group consisting of a nitrogen atom and four groups, wherein each group is attached to nitrogen by a carbon atom. The term "long alkyl group" or chain refers to an alkyl group or chain that is substituted on the nitrogen atom of a quaternary ammonium group or exists as a substituent of pyridinium and has a carbon atom between 4 and 24. In some embodiments, an alkyl group is an alkyl group with 4 to 18 carbon atoms. In some embodiments, an alkyl group is an alkyl group with 4 to 8 carbon atoms. In some embodiments, an alkyl group is an alkyl group with 4 to 10 carbon atoms. In other embodiments, an alkyl group is an alkyl group with 6, 7 or 8 carbon atoms, wherein each possibility represents a separate embodiment of the present invention.

[0421] Aggregable Unit

[0422] In some embodiments, the polymerizable unit is represented by structure (7):

[0423]

[0424] in

[0425] L7 is the first linker or bond;

[0426] L8 is a third linker or bond;

[0427] X7 is a bond, alkylene, arylene, alkenylene, alkynylene or any combination thereof;

[0428] X8 is none or hydrogen;

[0429] Z3 is a functional polymerizable group or more than one functional polymerizable group (the more than one functional polymerizable groups are connected by a linker), wherein each functional polymerizable group is independently selected from the group consisting essentially of: a substituted or unsubstituted acrylate, a substituted or unsubstituted epoxy, a substituted or unsubstituted vinyl or an isocyanate moiety, wherein each substituent is an alkyl, alkoxy, haloalkyl, halide, cycloalkyl, aryl, heterocycle or C(=O)O(alkyl); and

[0430] concept Represents a covalent bond to an organic or inorganic core.

[0431] Non-limiting examples of the epoxy group of Z3 (which may be substituted in certain embodiments) include 3-glycidyloxypropyl.

[0432] Nonlimiting examples of the vinyl group of Z3 include unsubstituted or substituted vinyl groups.

[0433] In another embodiment, Z3 is -OC(O)-CH=CH2(acrylate); -OC(O)-C(CH3)=CH2(methacrylate); (epoxy); -CH=CH2 (vinyl) or -N=C=O (isocyanate). In another embodiment, Z3 is more than one functional polymerizable group, and the more than one functional polymerizable groups are connected by a linker. In yet other embodiments, Z3 is -(CH=CH) 1-6 -CH=CH2 (oligoacetylene); or

[0434]

[0435] (Pentaerythritol triacrylate).

[0436] In another embodiment, the polymerizable unit is Si-alkylene-OC(O)-CH=CH2(Si-acrylate); (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); (N-epoxy); {N}-alkylene-CH=CH2 (N-vinyl), {N}-CH=CH2 (N-direct-vinyl) or {N}-alkylene-N=C=O (N-isocyanate); wherein "alkylene" may include an ether oxygen, as in, for example, 3-glycidyloxypropyl (epoxy moiety); wherein "Si" is part of the siloxane moiety directly attached to the core; and "{N}" is a nitrogen-containing (containing a nitrogen atom) linker, such as an amide, amine, guanidine, imidazole, etc.

[0437] A non-limiting example of an epoxy group of the polymerizable unit (which may be substituted in certain embodiments) includes 3-glycidyloxypropyl.

[0438] 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.

[0439] In one embodiment, X8 is none or hydrogen. Each possibility represents a separate embodiment of the present invention.

[0440] In some embodiments of polymerizable units, L7 or L8 are each independently the same or different linkers. In some embodiments, L7 and L8 are connected to each other in any possible way. In some embodiments, L8 is nothing (or a key), and L7 is covalently connected to the core. In another embodiment, L8 is covalently connected to the core, and L7 is connected to L8. In another embodiment, L7 is connected to X7, X8 and L8 or the core. In another embodiment, "linker" includes any possible chemical part that can connect at least two other chemical parts adjacent to such a linker. In other embodiments, 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 phosphate, phosphonate, siloxane, silane, ether, acetal, amide, amine, anhydride, ester, ketone or one or more aromatic rings functionalized with any of the aforementioned parts. Each possibility represents a separate embodiment of the present invention.

[0441] 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 (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.

[0442] In another embodiment, L7, L8, X7, X8 or any combination thereof is C1 to C18 alkylene, alkenylene, alkynylene or aryl substituted by at least one carboxyl moiety, wherein the carboxyl terminal is attached to the core. They can be derived from C1-C18 alkylene substituted by at least one carboxyl moiety and having an amino terminal, which is functionalized, for example, with an alkylene terminated by epoxy, acrylate, isocyanate or vinyl. The connector can be derived from an amino acid (polypeptide) with a chain length between 2 and 18 carbon atoms from a natural or synthetic source, or an acyl halide of the amino acid. Non-limiting examples of such amino acids are 18-aminooctadecanoic acid and 18-aminostearic acid.

[0443] In another embodiment, L7, L8, X7, X8 or any combination thereof is C1 to C18 alkylene, alkenylene, alkynylene, arylene or aryl. The linker may be derived from a dihaloalkylene or dihaloarylene group, which is functionalized at each end by replacing the halogen moiety with a functional group bound to the core and replacing the halogen moiety to obtain an epoxy, acrylate, isocyanate or vinyl moiety, respectively, with a core and a functional polymerizable group.

[0444] In another embodiment, L7, L8, X7, X8 or any combination thereof is an aromatic group derived from the non-limiting examples of 4,4-bisphenol, dibenzoic acid, dibenzoic acid halide, dibenzoic acid sulfonate, terephthalic acid, terephthalic acid halide and terephthalic acid sulfonate. The linker is functionalized by the core and the functional polymerizable group respectively through the functional groups of the aromatic groups mentioned herein (e.g., hydroxyl, carboxyl or sulfonate).

[0445] In another embodiment, L7, L8, X7, X8 or any combination thereof is a siloxane group or a silane group derived from 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 by its functional group (e.g., hydroxyl, siloxane, carboxyl, amide or sulfonate) respectively by the core and the functional polymerizable group.

[0446] General definition of the particles according to the invention

[0447] In some embodiments, the antimicrobial unit within the antimicrobial particles of the present invention comprises an antimicrobial group comprising a tertiary amine or tertiary ammonium; or a quaternary ammonium and / or pyridinium, such as represented by the following formula:

[0448] - + 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')-,

[0449]

[0450] in:

[0451] R1-R 11 and R1'-R 11 ' is as described above.

[0452] In one other embodiment, the activity of the quaternary ammonium, tertiary amine or tertiary ammonium or pyridinium remains strong at any pH.

[0453] In some embodiments, the polymerizable unit within the antimicrobial particles of the present invention is Si-alkylene-OC(O)-CH=CH2(Si-acrylate); (Si-epoxy); Si-alkylene-CH=CH2 (Si-vinyl); Si-alkylene-N=C=O (Si-isocyanate), {N}-alkylene-OC(O)-CH=CH2 (N-acrylate); (N-epoxy); {N}-alkylene-CH=CH2 (N-vinyl) or {N}-alkylene-N=C=O (N-isocyanate); wherein "Si" is part of the siloxane portion directly attached to the core; and "{N}" is a nitrogen-containing (containing a nitrogen atom) linker, such as amide, amine, guanidine, imidazole, etc.

[0454] As used herein, unless otherwise specified, the term "alkyl" or "alkylene" refers to any straight or branched alkyl group containing up to about 24 carbons. In one embodiment, the alkyl group includes C1-C3 carbons. In one embodiment, the alkyl group includes C1-C4 carbons. In one embodiment, the alkyl group includes C1-C5 carbons. In another embodiment, the alkyl group includes C1-C6 carbons. In another embodiment, the alkyl group includes C1-C8 carbons. In another embodiment, the alkyl group includes C1-C 10 In another embodiment, the alkyl group includes C1-C 12 In another embodiment, the alkyl group includes C4-C8 carbon. In another embodiment, the alkyl group includes C4-C 10 In another embodiment, the alkyl group includes C4-C 18 In another embodiment, the alkyl group includes C4-C 24 In another embodiment, the alkyl group includes C1-C 18 In another embodiment, the alkyl group includes C2-C 18 In 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 can be unsubstituted. In another embodiment, the alkyl group can be substituted with halogen, haloalkyl, hydroxy, alkoxy, carbonyl, amido, alkylamido, dialkylamido, cyano, nitro, CO2H, amino, alkylamino, dialkylamino, carboxyl, thio and / or thioalkyl. In another embodiment, the alkyl is a 2,2-disubstituted C3-C 20 The term "2,2-disubstituted C3-C 20"Alkyl" refers to an alkyl group as described herein, which has between 3 and 20 carbons and is substituted three times at the second carbon (starting from the point of attachment) by halogen, haloalkyl, alkyl, alkoxy, carbonyl, amido, alkylamido, dialkylamido, cyano, nitro, CO2H, amino, alkylamino, dialkylamino, carboxyl, thio and / or thioalkyl, wherein such substitutions may be the same or different; or alternatively, the alkyl group is substituted once at the second carbon by oxo (=O) or by other double bonds to elements (e.g., S) or moieties (e.g., vinyl carbon or NH), and it is further substituted by substituents selected from the above list of the first possibility; in all cases - there is no hydrogen available for abstraction at the second carbon position (e.g., there is no hydrogen at this position, only non-hydrogen substituents). 2,2-disubstituted C3-C 20 Non-limiting examples of alkyl groups include neopentyl (-CH2-C(CH3)3), -CH2-C(CH3)2-CH2CH3, CH2-CF2CH3, and -CH2C(=O)CH3. In another embodiment, the alkyl group is a 2,2-disubstituted C3-C8 alkyl group. In another embodiment, the alkyl group is a 2,2-disubstituted C3-C 10 In another embodiment, the alkyl group is a 2,2-disubstituted C3-C 12 In another embodiment, the alkyl group is a 2,2-disubstituted C3-C 18 The terms "2,2-disubstituted C3-C8 alkyl", "2,2-disubstituted C3-C 10 Alkyl", "2,2-disubstituted C3-C 12 Alkyl" and "2,2-disubstituted C3-C 18 "Alkyl" refers to "2,2-disubstituted C3-C 20 "alkyl" similar part, but respectively having C3-C8 alkyl, C3-C 10 Alkyl, C3-C 12 Alkyl and C3-C 18 In another embodiment, the alkylene group is a 2,2-disubstituted C2-C 20 The term "2,2-disubstituted C2-C 20 "Alkylene" refers to "2,2-disubstituted C3-C 20 "alkyl" moieties, but with an alkylene group as described herein having between 2 and 20 carbons. 2,2-disubstituted C2-C 20Non-limiting examples of alkylene groups include neopentylene (-CH2-C(CH3)2-CH2-), -CH2-C(CH3)2-CH2CH2-, -CH2-CF2CH2-, and -CH2C(=O)CH2-. In another embodiment, the alkylene group is a 2,2-disubstituted C2-C8 alkylene group. In another embodiment, the alkylene group is a 2,2-disubstituted C2-C8 alkylene group. 10 In another embodiment, the alkylene group is a 2,2-disubstituted C2-C 12 In another embodiment, the alkylene group is a 2,2-disubstituted C2-C 18 The term "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 "Alkylene" refers to "2,2-disubstituted C2-C 20 "Alkylene" similar part, but respectively having C2-C8 alkylene, C2-C 10 Alkylene, C2-C 12 Alkylene and C2-C 18 Alkylene.

[0455] In another embodiment, the alkyl group is a 2,2,2-trisubstituted ethyl group. The term "2,2,2-trisubstituted ethyl group" refers to an ethyl group that is substituted three times at the second carbon (starting from the point of attachment) by halogen, haloalkyl, alkoxy, carbonyl, amido, alkylamido, dialkylamido, cyano, nitro, CO2H, amino, alkylamino, dialkylamino, carboxyl, thio and / or thioalkyl, wherein such substitutions may be the same or different; or alternatively, the ethyl group is substituted once at the second carbon by oxo (=O) or by other double bonds to elements (e.g., S) or moieties (e.g., vinyl carbon or NH), and it is further substituted by a substituent selected from the above list of the first possibility; in all cases - there is no hydrogen available for extraction at the second carbon position (e.g., there is no hydrogen at this position, only non-hydrogen substituents). Non-limiting examples of 2,2,2-trisubstituted ethyl groups include 2,2,2-trihaloethyl and -CH2C(=O)-NH2. In another embodiment, the hydrophobic alkyl group refers to an alkyl group having at least four carbon atoms. In another embodiment, the hydrophobic alkyl group refers to a C4-C 24In 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.

[0456] As used herein, term " aryl " refers to being directly bonded to another group and can be substituted or unsubstituted any aromatic ring.As used herein, term " arylene " refers to wherein it is directly bonded to any aromatic ring of two groups (for example, arylene is for example phenylene, -C6H4-).In another embodiment, arylene can be directly bonded to more than two groups.Aryl group or arylene group can be unique substituent, or aryl group or arylene group can be the component of larger substituent, such as in arylalkyl, arylamino, arylamido etc.Exemplary aryl (and similarly, arylene) group includes but is not limited to phenyl, tolyl, xylyl, furanyl, naphthyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, triazinyl, thiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, thienyl, pyrrolyl, phenylmethyl, phenylethyl, phenylamino, phenylamido etc. Substituents 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, a hydrophobic aryl or arylene group refers to an aryl or arylene group having at least six carbons.

[0457] As used herein, the term "benzyl" refers to a -CH2-C6H5 moiety and 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), hydroxy, -OC(O)CF3, -OCHTh, -NHCO-alkyl, COOH, -C(O)Ph, C(O)O-alkyl, C(O)H, or -C(O)NH2. Similarly, "benzylidene" refers to a -CH2-C6H4- moiety and may be unsubstituted or substituted with the substituents described above for the benzyl moiety.

[0458] As used herein, the term "haloalkyl" refers to an alkyl group as described above and substituted at least once by a halide (e.g., F, Cl, Br or I). In one embodiment, the alkyl group is all substituted by a halide, e.g., hydrogen is not present in the haloalkyl group, and is referred to as a "perhaloalkyl group" (e.g., CF3: perfluoromethyl or CCl3: perchloromethyl). In one embodiment, only a portion of the alkyl group is substituted by a halide (e.g., CH2CF3). In another embodiment, the non-limiting examples of haloalkyl groups include: CF3, CCl3, CH2CF3, CF2CF3, CCl2CCl3 and CI3.

[0459] The term "alkenyl" or "alkenylene" refers to a substance comprising at least two carbon atoms and at least one double bond. The term "1-alkenyl" or "1-alkenylene" refers to the same, wherein the double bond is on the first carbon (from the point of attachment). The term "2-alkenyl" or "2-alkenylene" refers to the same, wherein the double bond is on the second carbon (from the point of attachment). The term "3-alkenyl" or "3-alkenylene" refers to the same, wherein the double bond is on the third carbon (from the point of attachment). In one embodiment, the alkenyl has 2-7 carbon atoms. In another embodiment, the alkenyl has 2-12 carbon atoms. In another embodiment, the alkenyl has 2-10 carbon atoms. In another embodiment, the alkenyl has 3-6 carbon atoms. In another embodiment, the alkenyl has 2-4 carbon atoms. In another embodiment, the alkenyl has 4-8 carbon atoms. In another embodiment, hydrophobic alkenyl refers to an alkenyl having at least four carbons. In another embodiment, the hydrophobic alkenyl group refers to a C4-C8 alkenyl group.

[0460] The term "alkynyl" or "alkynylene" refers to a substance comprising at least two carbon atoms and at least one triple bond. The term "1-alkynyl" or "1-alkynylene" refers to the same, wherein the triple bond is on the first carbon (from the point of attachment). The term "2-alkynyl" or "2-alkynylene" refers to the same, wherein the triple bond is on the second carbon (from the point of attachment). The term "3-alkynyl" or "3-alkynylene" refers to the same, wherein the triple bond is on the third carbon (from the point of attachment). In one embodiment, the alkynyl has 2-7 carbon atoms. In another embodiment, the alkynyl has 2-12 carbon atoms. In another embodiment, the alkynyl has 2-10 carbon atoms. In another embodiment, the alkynyl has 3-6 carbon atoms. In another embodiment, the alkynyl has 2-4 carbon atoms. In another embodiment, the alkynyl has 3-6 carbon atoms. In another embodiment, the alkynyl has 4-8 carbon atoms. In another embodiment, a hydrophobic alkynyl refers to an alkynyl having at least four carbons. In another embodiment, the hydrophobic alkynyl group refers to a C4-C8 alkynyl group.

[0461] In one embodiment, the term "alkoxy" refers to an alkyl group as defined above bonded to oxygen. Non-limiting examples of alkoxy groups include methoxy, ethoxy, and isopropoxy.

[0462] In one embodiment, a "cycloalkyl" group refers to a ring structure containing carbon atoms as ring atoms, which 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 by halogen, alkyl, haloalkyl, hydroxy, 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), cyclooctenyl (COE) and the like. In another embodiment, hydrophobic cycloalkyl refers to a cycloalkyl with at least six carbons. In one embodiment, a "cycloalkylene" group refers to the same definition as "cycloalkyl" above, but the cycloalkylene is directly bonded to two groups (e.g., -cyclohexylene-, -C6H 10 -). In another embodiment, the cycloalkylene group is directly bonded to more than two groups.

[0463] In one embodiment, a "heterocyclic" group refers to a ring structure that contains sulfur, oxygen, nitrogen, or any combination thereof as part of the ring in addition to carbon atoms. In another embodiment, the heterocyclic ring is a 3-12 ring. In another embodiment, the heterocyclic ring is a 6-ring. In another embodiment, the heterocyclic ring is a 5-7 ring. In another embodiment, the heterocyclic ring is a 3-8 ring. In another embodiment, the heterocyclic group can be unsubstituted or substituted by halogen, alkyl, haloalkyl, hydroxyl, alkoxy, carbonyl, acylamino, alkylacylamino, dialkylacylamino, cyano, nitro, CO2H, 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 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, a hydrophobic heterocyclic group refers to a heterocyclic ring having at least six carbon atoms. In one embodiment, the heterocyclic ring is directly bonded to a group (e.g., pyridyl, In one embodiment, the heterocycle is directly bonded to two groups (e.g., pyridinyl, ). In one embodiment, the heterocycle is directly bonded to more than two groups.

[0464] The term "hydrophobic" refers to an alkyl, alkenyl or alkynyl group having at least four carbons, or the term "hydrophobic" refers to a terpenoid, refers to a cycloalkyl, aryl or heterocyclic group having at least six carbons. Each possibility represents a separate embodiment of the present invention.

[0465] The antimicrobial groups of the present invention (e.g., the antimicrobial groups of all antimicrobial active units, above sections "A)"-"C)") are chemically bound to the core at a surface density of at least one antimicrobial group per 10 square nanometers of core surface. In another embodiment, at least 1 antimicrobial group per 1 square nanometer of core surface. In another embodiment, there are between 0.001-300 antimicrobial groups per square nanometer of core surface. In another embodiment, there are between 0.001-250 antimicrobial groups per square nanometer of core surface. In another embodiment, there are between 0.001-200 antimicrobial groups per square nanometer of core surface. In another embodiment, there are between 0.001-150 antimicrobial groups per square nanometer of core surface. In another embodiment, there are between 0.001-100 antimicrobial groups per square nanometer of core surface. In another embodiment, there are between 0.001-50 antimicrobial groups per square nanometer of core surface. In another embodiment, the core surface of each square nanometer has an antimicrobial group between 0.001-20. In another embodiment, the core surface of each square nanometer has an antimicrobial group between 0.001-17. In another embodiment, the core surface of each square nanometer has an antimicrobial group between 0.001-15. In another embodiment, the core surface of each square nanometer has an antimicrobial group between 0.001-10. In another embodiment, the core surface of each square nanometer has an antimicrobial group between 0.001-4. In another embodiment, the core surface of each square nanometer has an antimicrobial group between 0.001-1. In another embodiment, the core surface of each square nanometer has an antimicrobial group between 50-100. In another embodiment, the core surface of each square nanometer has an antimicrobial group between 100-150. In another embodiment, the core surface of each square nanometer has an antimicrobial group between 150-200. In another embodiment, the core surface of each square nanometer has an antimicrobial group between 200-250. In another embodiment, the core surface of every square nanometer has an antimicrobial group between 250-300. In another embodiment, the core surface of every square nanometer has an antimicrobial group between 1-4. In another embodiment, the core surface of every square nanometer has an antimicrobial group between 1-6. In another embodiment, the core surface of every square nanometer has an antimicrobial group between 1-20. In another embodiment, the core surface of every square nanometer has an antimicrobial group between 1-10. In another embodiment, the core surface of every square nanometer has an antimicrobial group between 1-15. Every possibility represents a separate embodiment of the present invention.

[0466] In some embodiments, the number of antimicrobial groups (e.g., as represented in sections "A)"-"C)" above) per antimicrobial active unit [(n1+n2)×m] is between 1-200. In another embodiment, the number of antimicrobial groups per antimicrobial active unit is between 1-150. In another embodiment, the number of antimicrobial groups per antimicrobial active unit is between 1-100. In another embodiment, the number of antimicrobial groups per antimicrobial active unit is between 1-50. In another embodiment, the number of antimicrobial groups per antimicrobial active unit is between 1-30. In another embodiment, the number of antimicrobial groups per antimicrobial active unit is between 1-20. In another embodiment, the number of antimicrobial groups per antimicrobial active unit is between 1-10. In another embodiment, the number of antimicrobial groups per antimicrobial active unit is between 50-100. In another embodiment, the number of antimicrobial groups per antimicrobial active unit is between 100-150. In another embodiment, the number of antimicrobial groups per antimicrobial active unit is between 150 and 200. Each possibility represents a separate embodiment of the present invention.

[0467] In some embodiments, the number of monomer units per antimicrobial active unit (e.g., as represented by the above sections "A)"-"C)") is between 1-200. In another embodiment, the number of monomer units per antimicrobial active unit is between 1-150. In another embodiment, the number of monomer units per antimicrobial active unit is between 1-100. In another embodiment, the number of monomer units per antimicrobial active unit is between 1-50. In another embodiment, the number of monomer units per antimicrobial active unit is between 1-30. In another embodiment, the number of monomer units per antimicrobial active unit is between 1-20. In another embodiment, the number of monomer units per antimicrobial active unit is between 1-10. In another embodiment, the number of monomer units per antimicrobial active unit is between 50-100. In another embodiment, the number of monomer units per antimicrobial active unit is between 100-150. In another embodiment, the number of monomer units per antimicrobial active unit is between 150-200. Each possibility represents a separate embodiment of the present invention.

[0468] In one embodiment, n1 is between 0-200. In another embodiment, n1 is between 0-10. In another embodiment, n1 is between 10-20. In another embodiment, n1 is between 20-30. In another embodiment, n1 is between 30-40. In another embodiment, n1 is between 40-50. In another embodiment, n1 is between 50-60. In another embodiment, n1 is between 60-70. In another embodiment, n1 is between 70-80. In another embodiment, n1 is between 80-90. In another embodiment, n1 is between 90-100. In another embodiment, n1 is between 100-110. In another embodiment, n1 is between 110-120. In another embodiment, n1 is between 120-130. In another embodiment, n1 is between 130-140. In another embodiment, n1 is between 140-150. In another embodiment, n1 is between 150-160. In another embodiment, n1 is between 160-170. In another embodiment, n1 is between 170-180. In another embodiment, n1 is between 180-190. In another embodiment, n1 is between 190-200. Each possibility represents a separate embodiment of the present invention.

[0469] In one embodiment, n2 is between 0-200. In another embodiment, n2 is between 0-10. In another embodiment, n2 is between 10-20. In another embodiment, n2 is between 20-30. In another embodiment, n2 is between 30-40. In another embodiment, n2 is between 40-50. In another embodiment, n2 is between 50-60. In another embodiment, n2 is between 60-70. In another embodiment, n2 is between 70-80. In another embodiment, n2 is between 80-90. In another embodiment, n2 is between 90-100. In another embodiment, n2 is between 100-110. In another embodiment, n2 is between 110-120. In another embodiment, n2 is between 120-130. In another embodiment, n2 is between 130-140. In another embodiment, n2 is between 140-150. In another embodiment, n2 is between 150-160. In another embodiment, n2 is between 160-170. In another embodiment, n2 is between 170-180. In another embodiment, n2 is between 180-190. In another embodiment, n2 is between 190-200. Each possibility represents a separate embodiment of the present invention.

[0470] In one embodiment, m is between 1-200. In another embodiment, m is between 1-10. In another embodiment, m is between 10-20. In another embodiment, m is between 20-30. In another embodiment, m is between 30-40. In another embodiment, m is between 40-50. In another embodiment, m is between 50-60. In another embodiment, m is between 60-70. In another embodiment, m is between 70-80. In another embodiment, m is between 80-90. In another embodiment, m is between 90-100. In another embodiment, m is between 100-110. In another embodiment, m is between 110-120. In another embodiment, m is between 120-130. In another embodiment, m is between 130-140. In another embodiment, m is between 140-150. In another embodiment, m is between 150-160. In another embodiment, m is between 160-170. In another embodiment, m is between 170-180. In another embodiment, m is between 180-190. In another embodiment, m is between 190-200. Each possibility represents a separate embodiment of the present invention.

[0471] In another embodiment, the antimicrobial groups of the present invention may be selected from: (a) quaternary ammonium groups comprising at least one terpenoid moiety or one hydrophobic group; and (b) pyridinium groups. Each possibility represents a separate embodiment of the present invention.

[0472] The term "nanoparticle" as used herein refers to a particle having a size of less than about 1,000 nm. The term "microparticle" as used herein refers to a particle having a size of about 1,000 nm or more.

[0473] The antimicrobial particles of the present invention are characterized by having a diameter between about 5nm and about 100,000nm, and therefore encompass both nanoparticle compositions and microparticle compositions. For example, the particle can be between about 10nm and about 50,000nm. In other embodiments, the diameter of the particle is greater than 1,000nm. In other embodiments, the diameter of the particle is greater than 10,000nm. In other embodiments, the diameter of the particle is between 1,000nm and 50,000nm. In other embodiments, the diameter of the particle is between 5nm and 250nm. In other embodiments, the diameter of the particle is between 5nm and 500nm. In another embodiment, the diameter of the particle is between 5nm and 1000nm. It will be apparent to those skilled in the art that other particle size ranges are applicable and are encompassed within the scope of the present invention.

[0474] The antimicrobial groups of the present invention may be in the form of quaternary ammonium salts or pyridinium salts as described above. Since any such groups are positively charged, their charge is balanced with anions. Non-limiting examples of anions include: halides, such as fluoride, chloride, bromide or iodide and fluoride; bicarbonate, nitrate, phosphate, acetate, fumarate, succinate, mesylate, trifluoromethanesulfonate, toluenesulfonate, tetrafluoroborate, hexafluorophosphate and sulfate. Each possibility represents a separate embodiment of the present invention.

[0475] In some embodiments, the term "quaternary ammonium group" refers to an atom group consisting of a nitrogen atom and four substituents (different from hydrogen) attached thereto. In another embodiment, "quaternary ammonium group" refers to an atom group consisting of a nitrogen atom and four groups, wherein each group is attached to nitrogen by a carbon atom. In some embodiments, the quaternary ammonium group provided herein includes at least one long alkyl chain. In some embodiments, the quaternary ammonium group provided herein includes at least one terpenoid. The term "long alkyl group" or chain refers to an alkyl group or chain that is substituted on the nitrogen atom of the quaternary ammonium group and has between 4 and 24 carbon atoms. In some embodiments, the alkyl group is an alkyl group with 4 to 18 carbon atoms. In some embodiments, the alkyl group is an alkyl group with 4 to 8 carbon atoms. In some embodiments, the alkyl group is an alkyl group with 4 to 10 carbon atoms. In other embodiments, the alkyl group is an alkyl group with 6, 7 or 8 carbon atoms, wherein each possibility represents a separate embodiment of the present invention.

[0476] Antimicrobial groups including terpenoid groups

[0477] In one embodiment, the antimicrobial groups of the present invention as described above for antimicrobial particles and antimicrobial active units thereof (e.g., Formula (I)-(VI), Formula (I)-(VII), Formula (IA)-(IE), Formula (IF1)-(IF2), Formula (IG1)-(IG2), Formula (I1)-(IH2) and Formula IJ) comprise at least one terpenoid group. In another embodiment, the antimicrobial group is selected from: (a) a tertiary amine (R3 and / or R3' is none) or a tertiary ammonium (R3 and / or R3' is H) comprising at least one terpenoid portion; and (b) a quaternary ammonium group comprising at least one terpenoid portion. In another embodiment, when the antimicrobial group of the present invention comprises at least one terpenoid group and / or R1, R2, R3 and / or R1', R2', R3' of the antimicrobial group as defined above are terpenoid portions, the core of the particle of the present invention is a polyhedral oligomeric silsesquioxane (POSS).

[0478] In some embodiments, the antimicrobial groups of formula (1) to (6) are selected from: (a) tertiary amines (R3 and / or R3' are absent) or tertiary ammoniums (R3 and / or R3' are H), wherein each nitrogen atom of the tertiary amine / tertiary ammonium has at least one bond to X1 or X2 and one bond to the terpenoid portion; (b) tertiary amines (R3 and / or R3' are absent) or tertiary ammoniums (R3 and / or R3' are H) or salts of said tertiary amines, wherein each nitrogen atom of the tertiary amine / tertiary ammonium has one bond to X1 or X2 and two bonds to the terpenoid portion, which may be the same or different from each other; (c) quaternary ammonium groups, wherein each nitrogen atom of the quaternary ammonium group has at least one bond to X1 or X2 and one or two bonds to the terpenoid portion, which may be the same or different from each other; each possibility represents a separate embodiment of the present invention.

[0479] In one embodiment, the antimicrobial group [- + N(R4)(R5)(R6),- + N(R4')(R5')(R6'), R6, R8-R defined in Structure (I) and Structure (IE) 11 , R6' and / or R8'-R 11 ' is the terpene part.

[0480] In another embodiment, when the antimicrobial group of the present invention comprises at least one terpenoid group and / or R6, R8-R 11 , R6' and / or R8'-R 11 When the terpene moiety is present, the core of the particle of the present invention is a polyhedral oligomeric silsesquioxane (POSS).

[0481] The term "terpenoid", also known as "isoprenoid", refers to a large class of naturally occurring compounds derived from five-carbon isoprene units. A "terpenoid moiety" is derived from a terpenoid.

[0482] In some embodiments, the terpenoid moiety is a "terpene group", e.g., directly bonded to a group (e.g., cinnamyl: ); or "terpenoidylene", e.g., directly bonded to two groups (e.g., cinnamylene, e.g., ). In one embodiment, the terpenoid moiety is directly bonded to more than two groups. In one embodiment, the terpenoid moiety is a cinnamyl group or cinnamylene group derived from cinnamaldehyde, cinnamic acid, curcumin, viscidone or cinnamyl alcohol. In another embodiment, the terpenoid moiety is a bornyl group or bornylene group derived from camphor, 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.

[0483] Cinnamaldehyde is a natural aldehyde extracted from the genus Cinnamomum. It is known for its low toxicity and its effectiveness against a wide range of bacteria and fungi.

[0484] Camphor is present in the wood of camphor laurel (Cinnamomum camphora), and also in the wood of kapur trees. It also occurs in some other related trees in the Lauraceae family, such as Ocotea usambarensis, and in other natural sources. Camphor can also be produced synthetically from the oil of rosin. Camphor can exist as the R enantiomer or the S enantiomer, mixtures of enantiomers, and racemic mixtures. Each possibility represents a separate embodiment of the present invention.

[0485] Citral or 3,7-dimethyl-2,6-octadienal or lemonal is a mixture of two diastereomeric terpenes. The two compounds are double bond isomers. The E-isomer is called geranal or citral A. The Z-isomer is called neral or citral B. Citral is known to have antimicrobial activity.

[0486] Perillaldehyde, also known as perilla aldehyde, is the most abundant naturally occurring terpenoid in the annual herb Perilla frutescens, as well as in a variety of other plants and essential oils.

[0487] Other examples of terpenes include, but are not limited to, curcuminoids found in turmeric and mustard seeds, citronellal found in Cymbopogon citratus (lemongrass), and carvacrol found in Origanum vulgare (oregano), thyme, pepperwort, wild bergamot, and Lippia graveolens. Each possibility represents a separate embodiment of the present invention.

[0488] According to the above embodiments, the antimicrobially active terpenoid moiety is selected from the group consisting of:

[0489]

[0490]

[0491]

[0492] as well as

[0493]

[0494] Each possibility represents a separate embodiment of the present invention.

[0495] Non-limiting examples of antimicrobially active quaternary ammonium groups according to the principles of the present invention are:

[0496]

[0497]

[0498]

[0499]

[0500] in

[0501] R 2 is alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl, or any combination thereof;

[0502] R 3 is an alkyl group, a terpenoid moiety, a cycloalkyl group, an aryl group, a heterocycle, an alkenyl group, an alkynyl group, or any combination thereof;

[0503] R4 and R5 are independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 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 R is alkyl, aryl, cycloalkyl, heterocycle or any combination thereof.

[0504] Non-limiting examples of functionalized antimicrobially active tertiary amine groups or their protonated forms according to the principles of the present invention are:

[0505]

[0506]

[0507] as well as

[0508]

[0509] Where R 2 is alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof.

[0510] Inorganic movement

[0511] In one embodiment, the inorganic core of the particles of the invention comprises silica, a metal, a metal oxide or a zeolite. Each possibility represents a separate embodiment of the present invention.

[0512] In one embodiment, the core of the particles of the present invention comprises silicon dioxide (SiO2). The silicon dioxide can be in any form known in the art, non-limiting examples of which include polyhedral oligomeric silsesquioxane (POSS), amorphous silicon dioxide, dense silicon dioxide, aerogel silicon dioxide, porous silicon dioxide, mesoporous silicon dioxide and pyrogenic silicon dioxide. Each possibility represents a separate embodiment of the present invention.

[0513] The surface density of active groups on the particle surface may have a proportional effect on its antimicrobial activity. In another embodiment, the core of the particle of the present invention comprises a silicate (SiO4 4- ) glass or ceramic. Non-limiting examples of silicates include aluminosilicates, borosilicates, barium silicates, barium borosilicates, and strontium borosilicates. Each possibility represents a separate embodiment of the present invention.

[0514] In another embodiment, the core of the particle of the invention comprises a surface activated metal selected from the group consisting of silver, gold, platinum, palladium, copper, zinc and iron. Each possibility represents a separate embodiment of the invention.

[0515] In another embodiment, the core of the particles of the invention comprises a metal oxide selected from the group consisting of zirconium dioxide, titanium dioxide, vanadium dioxide, zinc oxide, copper oxide and magnetite. Each possibility represents a separate embodiment of the invention.

[0516] In one embodiment, the inorganic core is a polyhedral oligomeric silsesquioxane (POSS) core.

[0517] In some embodiments, provided herein is an antimicrobial particle comprising a POSS core, wherein each silicon atom of the POSS is functionalized by at least one antimicrobial group or by at least one functional polymerizable group, wherein the molar ratio of silicon atoms functionalized by at least one antimicrobial group and silicon atoms functionalized by 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 between 2:1 and 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 comprises 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') or -N(R1')-; wherein R1-R3 and R1'-R3' are as described above. In one embodiment, the antimicrobial group comprises a quaternary ammonium and / or pyridinium, such as represented by the following formula:

[0518]

[0519] in:

[0520] R4-R 11 and R4'-R 11 ' is as described above. In another embodiment, the antimicrobial group may be selected from: (a) a quaternary ammonium group comprising at least one terpenoid moiety or a hydrophobic group; and (b) a pyridinium group. Each possibility represents a separate embodiment of the present invention.

[0521] In one embodiment, the functional polymerizable groups include acrylate groups, epoxy groups, vinyl groups, and / or isocyanate groups.

[0522] In some embodiments, provided herein is an antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized by at least one quaternary ammonium group or by at least one functional polymerizable group, wherein the functional polymerizable group comprises an acrylate group, an epoxy group, an isocyanate group, or a vinyl group; wherein the number of quaternary ammonium groups per silicon atom is between 1 and 200, and wherein the molar ratio of silicon atoms functionalized by at least one quaternary ammonium group and silicon atoms functionalized by 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 between 2: 1 and 1: 2. Each possibility and subranges thereof represent a separate embodiment of the present invention.

[0523] In some embodiments, provided herein is an antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized by at least one quaternary ammonium group or by at least one functional polymerizable group, the functional polymerizable group comprising an acrylate group, an epoxy group, an isocyanate group, or a vinyl group; wherein the number of quaternary ammonium groups per silicon atom is between 2 and 200, and wherein the molar ratio of silicon atoms functionalized by at least one quaternary ammonium group and silicon atoms functionalized by 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 between 2: 1 and 1: 2. Each possibility and subranges thereof represent a separate embodiment of the present invention.

[0524] In some embodiments, the silicon atom of the POSS (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) that is connected to one or more quaternary ammonium groups via a linker. In other embodiments, the silicon atom is connected to the ammonium group via an alkylene group. Non-limiting examples include: Si-alkylene-[N + (R1)(R2)-alkylene] n -N + (R1)(R2)(R3), wherein n is between 1-200, and R1, R2, R3 are as described above. In other embodiments, n is between 2-200. In other embodiments, n is 1, 2, 3, 4, 5 or 6. In other embodiments, n is between 1-10, 2-10, 2-50, 2-5.

[0525] In some embodiments, provided herein is an antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized by an N-alkylated 3-(2-aminoethylamino)propyl group, wherein the propyl end group is attached to the silicon atom; or is functionalized by at least one functional polymerizable group selected from an acrylate group, an epoxy group, an isocyanate group, and a vinyl group; wherein the number of quaternary ammonium groups per silicon atom is between 2 and 200, and wherein the molar ratio of silicon atoms functionalized by N-alkylated 3-(2-aminoethylamino)propyl groups and silicon atoms functionalized by 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 between 2:1 and 1:2. Each possibility and its subranges represent a separate embodiment of the present invention.

[0526] In some embodiments, the silicon atom of the POSS (core of the antimicrobial particle) is functionalized by at least one functional polymerizable group, wherein the functional polymerizable group includes an acrylate group, an epoxy group, an isocyanate group, or a vinyl group. In one embodiment, "the silicon atom of the POSS (core of the antimicrobial particle) functionalized by at least one functional polymerizable group" refers to the silicon atom of the POSS (core), which is connected to an acrylate group, an epoxy group, an isocyanate group, or a vinyl group through a linker. In other embodiments, Si is connected to acrylate, epoxy, or vinyl via an alkylene group. Non-limiting examples of such silicon atom functionalization may include: Si-alkylene-OC(O)-CH=CH2 (Si-acrylate); (Si-epoxy); Si-alkylene-CH=CH2 (Si-vinyl) or Si-alkylene-N=C=O (Si-isocyanate). In some embodiments, the "Si" of the "(acrylate)" structure, "(epoxy)" structure, "(vinyl)" structure or "(isocyanate)" structure is an integral part of the inorganic core, and the Si atom is covalently bonded / linked to three oxygen atoms of the core (in addition to the covalent bonding / linkage to the "alkylene"). Each possibility represents a separate embodiment of the present invention.

[0527] In some embodiments, when the core is inorganic, the polymerizable unit is Si-alkylene-OC(O)-CH=CH2(Si-acrylate); (Si-epoxy); Si-alkylene-CH=CH2 (Si-vinyl) or Si-alkylene-N=C=O (Si-isocyanate), where "Si" is part of the siloxane portion directly attached to the core.

[0528] In some embodiments, provided herein is an antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized with at least one quaternary ammonium group or with propyl acrylate, wherein the propyl end group is attached to the silicon atom; wherein the number of quaternary ammonium groups per silicon atom is between 2 and 200, and wherein the molar ratio of silicon atoms functionalized with at least one quaternary ammonium group and silicon atoms functionalized with propyl acrylate 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 between 2:1 and 1:2. Each possibility and sub-ranges thereof represent a separate embodiment of the present invention.

[0529] In some embodiments, provided herein is an antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized by an N-alkylated 3-(2-aminoethylamino)propyl group, wherein the propyl end group is attached to the silicon atom; or functionalized by propyl acrylate, wherein the propyl end group is attached to the silicon atom; wherein the number of quaternary ammonium groups per silicon atom is between 2 and 200, and wherein the molar ratio of silicon atoms functionalized by N-alkylated 3-(2-aminoethylamino)propyl groups and silicon atoms functionalized by propyl acrylate 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 between 2:1 and 1:2. Each possibility and its subranges represent a separate embodiment of the present invention.

[0530] In some embodiments, the antimicrobial particles provided herein comprise an inorganic core or an organic core, wherein the molar ratio of the antimicrobial active unit to the polymerizable unit 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 sub-range thereof. In other embodiments, the antimicrobial unit comprises an antimicrobial group comprising a tertiary amine or tertiary ammonium; or a quaternary ammonium and / or pyridinium, such as represented by the following formula:

[0531] - + 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')-,

[0532]

[0533] in:

[0534] R1-R 11 and R1'-R 11 ' is as described above.

[0535] In one other embodiment, the activity of the quaternary ammonium, tertiary amine, tertiary ammonium or pyridinium remains strong at any pH.

[0536] 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 and silicon atoms (in the POSS) functionalized with at least one functional polymerizable group is between 10:1 and 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 sub-range thereof. In other embodiments, the antimicrobial group comprises a tertiary amine or tertiary ammonium; or a quaternary ammonium and / or pyridinium, such as represented by the following formula:

[0537] - + 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')-,

[0538]

[0539] in:

[0540] R1-R 11 and R1'-R 11 ' is as described above.

[0541] In one other embodiment, the activity of the quaternary ammonium, tertiary amine, tertiary ammonium or pyridinium remains strong at any pH.

[0542] In some embodiments, provided herein is an antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized by at least one antimicrobial group or by at least one functional polymerizable group, wherein the functional polymerizable group comprises an acrylate group, an epoxy group, an isocyanate group, or a vinyl group; and wherein the molar ratio of silicon atoms functionalized by at least one quaternary ammonium group and silicon atoms functionalized by 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 between 2: 1 and 1 : 2. Each possibility and subranges thereof represent a separate embodiment of the present invention.

[0543] In some embodiments, the silicon atom of the POSS (core) is connected to one or more quaternary ammonium groups or pyridinium groups, tertiary ammonium or tertiary amines through a linker. In other embodiments, Si is connected to the ammonium group / amine group via an alkylene group. Non-limiting examples of quaternary ammonium connected to Si atoms: Si-alkylene-[N + (R1)(R2)-alkylene] n -N + (R1)(R2)(R3), wherein n is between 1-200, and R1, R2, R3 are as described above. In another embodiment, the quaternary ammonium attached to the silicon atom is an N-alkylated 3-(2-aminoethylamino)propyl group, wherein the propyl group terminal is attached to the silicon atom. In other embodiments, the N-alkylated group includes C1-C18 alkyl units. In other embodiments, the N-alkylated group includes C1-C18 alkyl units, and at least one alkyl unit is a C4-C8 alkyl.

[0544] In some embodiments, each square nanometer (nm 2 The number of quaternary ammonium groups (=antimicrobial groups) on the surface of the POSS core is 100 nm2. 2 ) of the core surface of the particle has between 0.01-20 antimicrobial units. In another embodiment, each square nanometer (nm 2 The number of quaternary ammonium groups (=antimicrobial groups) on the surface of the POSS core is 100 nm2. 2) have between 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 on the core surface of the particle, each range representing a separate embodiment of the invention. The surface density of active groups on the particle surface has a proportional effect on its antimicrobial activity.

[0545] In one embodiment, the core of the antimicrobial particles of the present invention is a polyhedral oligomeric silsesquioxane (POSS), wherein at least one silicon atom of the polyhedral oligomeric silsesquioxane (POSS) is capped. In another embodiment, "capped" silicon in POSS means that the Si atom is not covalently linked / bonded to an antimicrobial active unit or a polymerizable unit, but rather the Si atom is, for example, covalently linked / bonded to hydrogen or an organic moiety, e.g., an alkyl group, an aryl group; etc. In another embodiment, the ratio of capped Si atoms to uncapped Si atoms 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 possibility represents a separate embodiment of the present invention.

[0546] For example, up to 70% of the Si atoms can be capped, for example, using methylated butyl groups, benzyl groups and / or propyl groups, which can be substituted or unsubstituted. In various embodiments, 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70% or any of the intermediate proportions of Si atoms can be capped.

[0547] With organic movement

[0548] 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 prepared from aliphatic monomers, which may be substituted with a variety of side groups, including (but not limited to) aromatic side groups. The aliphatic polymers that may be included in the particles according to the present invention contain nitrogen atoms (and other heteroatoms) as part of the polymer backbone. In one embodiment, the core of the particle is an organic polymer core that includes an amine that may be substituted with R1, R2 and / or R3 as defined with respect to Structure 1; or includes an imine that is chemically modified to an amine and then substituted with R1, R2 and / or R3 as defined with respect to Structure 1. In one embodiment, the core of the particle is an organic polymer core comprising as an antimicrobial group an amine which may be substituted with R4, R5, R6, R4', R5' and / or R6' as defined with respect to Structure I; or an imine which is chemically modified to an amine and then substituted with R4, R5, R6, R4', R5' and / or R6' as defined with respect to Structure I. In other embodiments, the antimicrobial group comprises a tertiary amine or tertiary ammonium; or a quaternary ammonium and / or pyridinium, such 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')-,

[0549]

[0550] in:

[0551] R1-R 11 and R1'-R 11 ' is as described above.

[0552] In one other embodiment, the activity of the quaternary ammonium, tertiary amine, tertiary ammonium or pyridinium can remain strong at any pH.

[0553] In one embodiment, the functional polymerizable groups include acrylate groups, epoxy groups, vinyl groups, or isocyanate groups.

[0554] In some embodiments, when the core is organic, the polymerizable unit comprises {N}-alkylene-OC(O)-CH=CH2(N-acrylate); (N-epoxy); {N}-alkylene-CH=CH2 (N-vinyl) or {N}-alkylene-N=C=O (N-isocyanate); wherein "Si" is part of the siloxane portion directly attached to the core; and "{N}" is a nitrogen-containing (containing a nitrogen atom) linker, such as amide, amine, guanidine, imidazole, etc.

[0555] Non-limiting examples of aliphatic polymers are polystyrene (PS), polyvinyl chloride (PVC), polyethyleneimine (PEI), polyethyleneamine (PVA), poly(allylamine) (PAA), poly(aminoethylacrylate), polypeptides with alkyl-amino side groups, chitosan and copolymers thereof (combinations). Each possibility represents a separate embodiment of the present invention. In one embodiment, the polymer is polyethyleneimine (PEI).

[0556] In another embodiment, the organic core includes at least one aromatic polymer selected from the group consisting of polystyrene, aminomethylated styrene polymers, aromatic polyesters, polyethylene terephthalate, and polyvinyl pyridine. For example, the at least one aromatic polymer may include polyethylene terephthalate.

[0557] In another embodiment, the polymer core can be directly (e.g., in Structure (1)-Structure (3): L3 is a bond) or connected via a linker to the antimicrobial active unit. In another embodiment, the polymer core can be directly (e.g., in Structure (I), Structure (IE), and Structure (II)-Structure (VII): L6 is a bond) or connected via a linker to the antimicrobial active unit. Each possibility represents a separate embodiment of the present invention.

[0558] In another embodiment, the polymer core may be attached to the polymerizable unit directly (eg, in structure (7): L8 is a bond) or via a linker. Each possibility represents a separate embodiment of the present invention.

[0559] In one embodiment, the organic polymer core comprises a combination of two or more different organic polymers. In another embodiment, the organic polymer core comprises a copolymer.

[0560] Resins / composites comprising the particles of the invention

[0561] In some embodiments, the antimicrobial particles of the present invention can be mixed with a polymer matrix to form a resin / composite material. In some embodiments, the functional polymerizable groups in the particles interact with the matrix and prevent the particles from leaching from the resin / composite material. In one embodiment, leaching is further prevented or reduced during polymerization (e.g., in vivo polymerization) of the functional polymerizable groups.

[0562] In some embodiments, the ratio between the antimicrobial active unit and the polymerizable unit can be in the range of 10: 1 to 1: 10 or more specifically in the range of 4: 1 to 1: 1. Surprisingly, such a ratio reduces the leakage of particles from the composite material by 1%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or intermediate values ​​compared to antimicrobial particles that do not include polymerizable units. In some embodiments, the ratio between the silicon atoms of the POSS (core) connected to the antimicrobial group (e.g., quaternary ammonium, tertiary amine, tertiary ammonium) and the silicon atoms of the POSS (core) connected to the functional polymerizable group (e.g., acrylate, epoxy, vinyl, isocyanate) can be in the range of 10: 1 to 1: 10 or more specifically in the range of 4: 1 to 1: 1. Surprisingly, such ratios reduce leakage of particles from the composite by 1%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or intermediate values ​​compared to antimicrobial particles that do not include functional polymerizable groups.

[0563] The particle of the present invention shows the antimicrobial activity of enhancement. Not subject to the constraint of any theory or mechanism, it can be assumed that such activity originates from the existence of the antimicrobial group of close packing on the surface of a given core, and the high density of the particle on the surface of the main material that is deposited. This density increases along with each antimicrobial activity unit in the particle of the present invention comprising the antimicrobial group of increasing number, and it produces the active functional polymerizable group of high local concentration, which causes the high effective concentration of the antimicrobial group, and enables to use a relatively small amount of particle to realize effective bacteria / microorganism annihilation. The close packing of the antimicrobial group is especially due to many antimicrobial activity units outstanding from each particle surface. Therefore, the antimicrobial group covers the most of available surface area (width dimension of the covering surface) of the particle. The surface density of the antimicrobial group causes the high effective concentration that promotes the antimicrobial inhibition effect. According to the principle of the present invention, the high surface density indicates high antimicrobial efficiency.

[0564] As described above, 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. Because the ammonium group / pyridinium group is positively charged, its charge is balanced with an anion. In certain embodiments, in the particles according to the present invention, the anion is a halide, such as fluoride, chloride, bromide or iodide. For example, the anion can be a fluoride. Other possible anions include, but are not limited to, bicarbonate, nitrate, phosphate, acetate, fumarate, succinate and sulfate. Every possibility represents a separate embodiment of the present invention.

[0565] The core of the particle as described above can generally be in the form selected from sphere, amorphous polygon, flaky (shallowflake-like) and rod.In some embodiments, the core is spherical, and has a diameter between about 5nm and about 100,000nm.In some embodiments, the core is spherical, and has a diameter between about 1000-100,000nm.In some embodiments, the core is spherical, and has a diameter between about 100-1000nm.In some other embodiments, the size of the particle is about 20nm to about 200nm.In some other embodiments, the size of the core is about 20nm to about 200nm.In some other embodiments, the size of the diameter of the core can be about 20nm to about 200nm.In another embodiment, the size of the diameter of the core can be about 20nm to about 200nm.In one embodiment, the core is POSS, and it is in the form selected from sphere, amorphous polygon, flaky and rod. In some representative embodiments, the POSS core is spherical and has a diameter between about 5nm and about 100,000nm. In some representative embodiments, the POSS core is spherical and has a diameter between about 1000-100,000nm. In some representative embodiments, the POSS core is spherical and has a diameter between about 100-10000nm. In some other embodiments, the size of the particle is about 20nm to about 200nm. In some other embodiments, the size of the core is about 20nm to about 200nm. In some other embodiments, the inorganic core is POSS, and the size of the particle is about 20nm to about 200nm. In another embodiment, the inorganic core is POSS, and the size of the core diameter is about 20nm to about 200nm. Each possibility represents a separate embodiment of the present invention.

[0566] Particular compositions comprising the particles of the invention

[0567] Some embodiments include compositions comprising one or more types of antimicrobial particles disclosed and polymeric materials / resins as matrix. For example, 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. Organic polymers can include hydrogels, polyolefins, epoxy resins, acrylate resins or any combination thereof. Inorganic polymers can include organosilicon polymers, ceramics, metals or any combination thereof.

[0568] In various embodiments, the weight ratio of particles to polymeric material can be any of the following: 0.25wt%-5wt%, 0.25wt%-1wt%, 1wt%-2wt%, 2wt%-3wt%, 3wt%-4wt%, 4wt%-5wt%, or in other sub-ranges thereof.

[0569] In some embodiments, the compositions provided herein are capable of filling tooth decay cavities, are dental restorative endodontic filling materials used to fill root canal spaces during root canal treatment, or are selected from the group consisting of dental restorative materials intended for temporary and final tooth restoration or tooth replacement, dental inlays, dental onlays, crowns, partial dentures, complete dentures, dental implants, dental implant abutments, and adhesives intended for permanent bonding of crowns, bridges, onlays, partial dentures, and orthodontic appliances to tooth enamel and dentin.

[0570] In some embodiments, the compositions provided herein further comprise fillers. In other embodiments, the compositions comprise 60% w / w-95% w / w fillers and 10% w / w-30% w / w resins / polymeric materials / matrix. In other embodiments, the compositions comprise 78.5% w / w fillers. In other embodiments, the compositions comprise 20% w / w resins / polymeric materials / matrix. In other embodiments, the compositions comprise 78.5% w / w fillers and 20% w / w resins / polymeric materials / matrix.

[0571] In some embodiments, the resin is prepared by mixing bisphenol A glycidyl ether dimethacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA), and urethane dimethacrylate (UDMA) to provide a clear blend; followed by mixing in camphorquinone (CQ), benzoin methyl ether (BME), ethyl 4-(dimethylamino)benzoate (EDB), and butylated hydroxytoluene (BHT) to provide the resin.

[0572] In some embodiments, the compositions provided herein comprise:

[0573] -CQ 0.05%w / w-0.5%w / w;

[0574] -BME 0.05%w / w-0.5%w / w;

[0575] -EDB 0.05%w / w-0.5%w / w;

[0576] -BHT 0.005%w / w-0.05%w / w;

[0577] -BisGMA 3%w / w-10%w / w;

[0578] -TEGDMA 3%w / w-10%w / w;

[0579] -UDMA 3% w / w-10% w / w;

[0580] - inorganic glass filler 60% w / w-95% w / w; and

[0581] - Antimicrobial particles 0.25% w / w - 5% w / w.

[0582] In some other embodiments, the compositions provided herein comprise:

[0583] -CQ 0.1% w / w;

[0584] -BME 0.1% w / w;

[0585] -EDB 0.1% w / w;

[0586] -BHT 0.01% w / ww / w;

[0587] -BisGMA 6.56% w / w;

[0588] -TEGDMA 6.56% w / w;

[0589] -UDMA 6.56% w / w;

[0590] - inorganic glass filler 78.5% w / w; and

[0591] - Antimicrobial particles 1.5% w / w.

[0592] In some embodiments, the composition of the present invention comprises the antimicrobial particles of the present invention and a polymer material comprising an organic polymer, an inorganic polymer or any combination thereof. In some embodiments, particles as described herein are dispersed in a polymer material. In another embodiment, particles are uniformly dispersed in a polymer material. In another embodiment, particles are present in the surface of a polymer material. In another embodiment, particles covalently interact with a polymer material. In another embodiment, antimicrobial particles are mechanically embedded in a polymer material. In another embodiment, these particles are three-dimensionally "locked" between polymer chains to prevent them from migrating out of a complex network. The strong hydrophobic properties of these particles also work in preventing particles from moving into a hydrophilic environment, such as in the case of physiological applications, dental applications, plastic surgery applications or other medical applications. In one embodiment, particles comprise functional polymerizable groups that can react with the part of a polymer material. In another embodiment, particles interact chemically with a polymer material. In another embodiment, particles comprise functional polymerizable groups that react with monomers to provide a polymer material of a composition. In other embodiments, in addition to the polymeric material of the composition (and / or in the case of a polymeric material with the composition), the particles also contain functional polymerizable groups that react with monomers to provide polymers. In one other embodiment, the reaction of the functional polymerizable groups with the polymeric material and / or monomers can be catalyzed and / or initiated by a catalyst and / or (photo) initiator. In other embodiments, 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 different particles.

[0593] In some embodiments, the composition of the present invention comprises the antimicrobial particles of the present invention and a polymer material comprising an organic polymer, an inorganic polymer or any combination thereof. In another embodiment, the polymer 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 polymethyl methacrylate, a polyurethane or any combination thereof. In another embodiment, the inorganic polymer comprises an organosilicon polymer such as polydimethylsiloxane (PDMS), ceramics, metals or any combination thereof. In another embodiment, the hydrogel is a poloxamer or alginate. In another embodiment, commercial poloxamer is used, or it is formed by a reaction between a polymer and other reagents. In another embodiment, the polymer is a poly(ethylene glycol) (PEG) having a reactive end group (such as an epoxide in PEG-diglycidyl ether), and the reagent has a plurality of reactive sites (e.g., diethylenetriamine). Each possibility represents a separate embodiment of the present invention.

[0594] In some embodiments, the weight ratio of particles to polymeric material is between 0.25% and 5%. In another embodiment, the weight ratio is between 0.5% and 2%. In another embodiment, the weight ratio is between 1% and 5%.

[0595] Another polymer material used in the context of the present invention is a resin used in dental, surgical, chirurgical and plastic composites. In such applications, the antimicrobial particles can be first dispersed in the resin portion, or added simultaneously with the filler or any other solid component (if any). Most of these resins are acrylic or epoxy type monomers that undergo polymerization in vivo. In some embodiments, the antimicrobial particles also undergo in vivo polymerization (regardless of the identity or presence of additional polymer materials of the matrix).

[0596] Process for preparing antimicrobial particles

[0597] Preparation of antimicrobial particles comprising one monomer unit per antimicrobially active unit

[0598] The particles of the present invention can be prepared according to a variety of processes, depending on the nature of the core, the antimicrobial active groups and the presence or absence of linkers. Some non-limiting examples of preparation methods are provided below.

[0599] In one embodiment, the present invention provides a process for preparing an antimicrobial particle, wherein the particle comprises at least one antimicrobial active unit and at least one polymerizable unit, wherein there is one monomer unit for each antimicrobial active unit. In a further embodiment, in the particles prepared by the process, the ratio between the number of antimicrobial units and the number of polymerizable units 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, or any range or subrange thereof. In the following, such a process will be presented in detail.

[0600] For standard particles, Figure 4 A representative method for preparing the particles of the present invention is depicted in , wherein the antimicrobial active group is a tertiary amine or quaternary ammonium group comprising at least one terpenoid moiety. Figure 4 , the core as defined herein is functionalized with a primary amine, and optionally the core already comprises (at least one) polymerizable unit covalently linked / bonded thereto (directly or indirectly via a linker as described herein). The primary amine reacts with an aldehyde to initially produce an imine (Schiff base) intermediate of formula (A'), which then reacts with a second aldehyde under reductive amination conditions to produce a tertiary amine of formula (B'). RC(=O)H and R'C(=O)H each represent an aldehyde which is a terpenoid or derived from a terpenoid. 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 involves the reaction of the tertiary amine with a group R 1 -Y reaction, where R 1 is C1-C4 alkyl, and Y is a leaving group such as halogen or sulfonate. In one embodiment, the core already includes (directly or indirectly via a linker as described herein) covalently linked / bonded to it (at least one) polymerizable unit. In another embodiment, the core is made of Figure 4 The particle (B' or C') produced by the above process depicted in is further reacted to provide the antimicrobial particle of the present invention, which comprises at least one antimicrobially active unit and at least one polymerizable unit.

[0601] It should be understood that the group Can represent any one or more of the following:

[0602] 1. An organic core directly bonded to NH2 and optionally directly bonded to a polymerizable unit or optionally indirectly bonded to the same unit (polymerizable unit) via a linker as described herein.

[0603] 2. An organic core that is bonded to NH2 via a linker as described herein and optionally directly to a polymerizable unit or optionally indirectly to the same unit (polymerizable unit) via a linker as described herein.

[0604] 3. An inorganic core directly bonded to NH2 and optionally directly bonded to a polymerisable unit or optionally indirectly bonded to the same unit (polymerisable unit) via a linker as described herein.

[0605] 4. An inorganic core bonded to NH2 via a linker as described herein and optionally directly to a polymerisable unit or optionally indirectly to the same unit (polymerisable unit) via a linker as described herein.

[0606] Example reaction ( Figure 4 ) can be a "one pot synthesis" or it can comprise two sequential reactions in which the intermediate formed in the first step is isolated. The first step is to form an intermediate (A') which is an imine (Schiff base) by reacting the amine functionalized core with a terpene moiety in the presence of a reducing agent (in this case with cinnamyl in the presence of NaBH4). If desired, the imine functionalized core can be isolated at this stage. Optionally, the intermediate (A') is further reacted with a terpene moiety in the presence of a reducing agent to produce a tertiary amine (B') comprising two terpene moieties. To obtain a quaternary ammonium, such as Figure 4 An additional alkylation step was performed as described in .

[0607] The particles with enhanced thermal stability can be prepared as described above with respect to standard particles and in Figure 4 with some notable differences: for the standard particles, R and R' are terpenoid moieties, in the case of 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, wherein R is alkyl, aryl, cycloalkyl, heterocycle or any combination thereof; R 1 Methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20alkyl, 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, wherein R is alkyl, aryl, cycloalkyl, heterocyclic, or any combination thereof. In this case of particles having enhanced thermal stability, the particles with R 1 The final reaction of -Y is mandatory and not optional in order to obtain ammonium. Figure 4 As mentioned in the process of the present invention, the core already includes (directly or indirectly via a linker as described herein) covalently connected / bonded to it (at least one) polymerizable unit. In another embodiment, the core is made of Figure 4 The particle (C') produced by the above process depicted in is further reacted to provide the antimicrobial particle of the present invention comprising at least one antimicrobially active unit and at least one polymerizable unit.

[0608] Figure 5 The process presented in for preparing standard particles uses cinnamaldehyde, but is applicable to other aldehydes. Thus, in some embodiments, the present invention provides a particle comprising (i) an inorganic core or an organic polymer core; (ii) an imine moiety chemically bound to the core, for example, at a surface density of at least one imine group per 10 square nanometers, wherein the imine group comprises a terpenoid moiety; and optionally (iii) covalently linked / bonded to (at least one) polymerizable unit of the core (directly or indirectly via a linker as described herein). The imine moiety is typically composed of Figure 4 The structure of formula (A') is shown in FIG. A more specific embodiment is Figure 5 The structure of formula (A) in . It will be appreciated by those skilled in the art that the present invention also encompasses other imine intermediate compounds comprising other terpenoid groups as described herein.

[0609] In one embodiment, Figure 5 The core in the process of already includes (directly or indirectly via a linker as described herein) covalently linked / bonded to it (at least one) polymerizable unit. In one other embodiment, the core of Figure 5 The particles produced by the above process depicted in (B or C) are further reacted to provide the antimicrobial particles of the present invention, which antimicrobial particles comprise at least one antimicrobially active unit and at least one polymerizable unit.

[0610] It should be understood that Figure 5 Group As mentioned above about Figure 4 Any of the meanings described.

[0611] Figure 6A-6C A representative method for preparing standard particles in which the antimicrobial active group is a quaternary ammonium group comprising an alkyl group having 4 to 18 carbon atoms is presented in . The method includes three approaches to prepare particles functionalized with quaternary ammonium salts (QAS). Figure 4 A) by first utilizing reductive amination to obtain a tertiary amine, followed by an alkylation reaction; Figure 4 B) by a stepwise alkylation reaction; and Figure 4 C) by reacting a linker functionalized with a leaving group (eg, Cl or another halogen) with a tertiary amine. 1 and R 2 represents a C1-C4 alkyl group such as methyl, ethyl, propyl or isopropyl. 1 and R 2 Can be different groups 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,

[0612] It should be understood that the group As mentioned above about Figure 4 A- Figure 4 C and Figure 5 Any of the meanings described.

[0613] In one embodiment, Figure 6A-6C The core in the process of already includes (directly or indirectly via a linker as described herein) covalently linked / bonded to it (at least one) polymerizable unit. In one other embodiment, the core of Figure 6A-6C The particles produced by the above process described in further react to provide the antimicrobial particles of the present invention, the antimicrobial particles comprising at least one antimicrobial active unit and at least one polymerizable unit. In some other embodiments, the further reactions are described in detail in the sections entitled "Solid Support Method as a Method for Preparing Antimicrobial Particles Comprising One Monomer Unit for Each Antimicrobial Active Unit" below; and "Solution Method as a Method for Preparing Antimicrobial Particles Comprising One Monomer Unit for Each Antimicrobial Active Unit".

[0614] It should be understood that the group Can represent any one or more of the following:

[0615] 1. An organic core directly bonded to Y and optionally directly bonded to a polymerisable unit or optionally indirectly bonded to the same unit (polymerisable unit) via a linker as described herein.

[0616] 2. An organic core bonded to Y via a linker as described herein and optionally directly to a polymerisable unit or optionally indirectly to the same unit (polymerisable unit) via a linker as described herein.

[0617] 3. An inorganic core directly bonded to Y and optionally directly bonded to a polymerisable unit or optionally indirectly bonded to the same unit (polymerisable unit) via a linker as described herein.

[0618] 4. An inorganic core bonded to Y via a linker as described herein and optionally directly to a polymerisable unit or optionally indirectly to the same unit (polymerisable unit) via a linker as described herein.

[0619] Figure 7A-7C A similar method for preparing particles with enhanced thermal stability is described in . This method includes three routes to prepare particles functionalized with quaternary ammonium salts (QAS). Fig. 7A ) by reaction with R1-Y / R2-Y to obtain a tertiary amine, followed by benzylation; Figure 7B ) through Fig. 7A ) in reverse order; and Figure 7C ): by reacting a linker functionalized with a leaving group (e.g., Cl or other halogen) with a tertiary amine. 4 and R 5 are independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 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. Y represents any leaving group, such as Cl, Br or I, or a sulfonate (e.g., mesyl, tosyl). In one embodiment, as described above with respect to Figure 4 - As mentioned in the process described in Figure 6, the core already includes (directly or indirectly via a linker as described herein) covalently linked / bonded to it (at least one) polymerizable unit. In one other embodiment, the core is made of Figure 7A-7CThe particles produced by the above process depicted in are further reacted to provide the antimicrobial particles of the present invention, which antimicrobial particles comprise at least one antimicrobially active unit and at least one polymerizable unit.

[0620] In some other embodiments, further reactions are described in detail in the sections entitled "Solid Support Method as a Method for Preparing Antimicrobial Particles Comprising One Monomer Unit for Each Antimicrobial Active Unit" and "Solution Method as a Method for Preparing Antimicrobial Particles Comprising One Monomer Unit for Each Antimicrobial Active Unit" below.

[0621] Core functionalization can occur via solid support methods or solution methods.

[0622] Solid support method as a method for preparing an antimicrobial containing one monomer unit per antimicrobial active unit Granular method

[0623] The preparation of functionalized standard particles is carried out in two general steps. First, the linker molecule is allowed to condense onto the particle surface via hydrolysis of the leaving group (surface functionalization) to give a Figure 8 , D') intermediate. Second, as ( Figure 4 - Figure 7) as mentioned in any one of the above, the functional sites of the linker molecule undergo further functionalization (linker functionalization) to give Figure 8 Functionalized particles of formula E'. Figure 8 The circle in the middle represents an organic or inorganic core; Q 1 , Q 2 and Q 3 are independently selected from the group consisting of ethoxy, methoxy, methyl, ethyl, hydrogen, sulfonate, and halide, wherein Q 1 , Q 2 and Q 3 At least one of 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 between 1 and 16. For clarity, the scheme presents the following case: wherein Q 1 , Q 2 and Q 3 represents the leaving group; Q 4 A similar process is used to prepare functionalized particles with enhanced thermal stability, with the difference being that W represents the same substituent except that the NH2 moiety is replaced with an arylene-NH2 or benzylidene-NH2 moiety. In one embodiment, the polymerizable unit is Figure 8 The solid support is added in a similar manner to the process; in this case, W in is a functional polymerizable group; Q 1 -Q3 is as indicated above; and the polymerizable unit addition (surface functionalization step) is performed before or after the core functionalization (surface + linker functionalization) with the antimicrobial unit. In another embodiment, when the polymerizable unit is added to the particle, the second step of linker functionalization is not performed, for example, when the polymerizable unit is introduced into the core / particle, only the step of "surface functionalization" is adopted.

[0624] Solution process as a method for preparing antimicrobial particles comprising one monomer unit per antimicrobially active unit Methods

[0625] In this method, the linker molecule is first functionalized with an antimicrobial active group to give a molecule of formula ( Figure 8 In the second stage, the intermediate (F') is allowed to settle onto the solid surface of the particles (surface functionalization) to give Figure 8 , E') functionalized particles.

[0626] For cinnamaldehyde standard particles, the process Fig. 9 exemplified in , but applicable to other aldehydes.

[0627] A similar process is used to prepare functionalized particles with enhanced thermal stability, with the difference being that W represents the same substituent except that the NH2 moiety is replaced with an arylene-NH2 or benzylidene-NH2 moiety. Figure 8-Figure 9 The solution carrier is added in a similar manner to the process; in this case, W in is a functional polymerizable group; Q 1 -Q 3 is as indicated above; and the polymerizable unit addition (surface functionalization step) is performed before or after the core functionalization (surface + linker functionalization) with the antimicrobial unit. In another embodiment, when the polymerizable unit is added to the particle, the first step of linker functionalization is not performed, for example, when the polymerizable unit is introduced into the core / particle, only the step of "surface functionalization" is adopted.

[0628] Preparation of antimicrobial particles comprising more than one monomer unit per antimicrobially active unit

[0629] In one embodiment, the present invention provides a process for preparing particles of the composite material of the present invention, wherein the particles contain more than one monomer unit per antimicrobial active unit. In a further embodiment, in the particles prepared by the process, the ratio between the number of antimicrobial units and the number of polymerizable units 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, or any range or subrange thereof. In the following, such a process will be presented in detail.

[0630] Solid support method as a method for preparing antimicrobial compositions containing more than one monomer unit per antimicrobial active unit Bioparticle Method

[0631] The solid support method involves several stages. First, for standard particles, the linker molecules (a few percent dilute solution) are allowed to condense onto the particle surface via (acid-catalyzed) hydrolysis of the leaving group (surface functionalization), resulting in attachment of the linker to the core ( Fig.10 , step 1). Second, the attached linker is elongated. In another embodiment, this stage is achieved synthetically via one or more steps. In another embodiment, the elongation is achieved by sequential addition of a difunctionalized alkane and a diaminoalkane, wherein the amine (of the attached linker and the diaminoalkane) attacks the electrophilic center of the difunctionalized alkane ( Fig.10 , steps 2 and 3). In another embodiment, such sequential additions are optionally repeated for 1-10 times. Finally, the antimicrobial active group (usually attached to an alkylene chain) is grafted to the resulting attached and extended linker. In another embodiment, the grafting is completed ( Fig.10 , step 4). For particles with enhanced thermal stability, a similar process is presented ( Fig.11 ), wherein the ammonium end of the antimicrobial active group is replaced by an aniline end, and R 1 -R 3 By R 4 -R 6 Replace. Fig.10 In, R 1 and R 2 are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, conjugated alkyl, alkenyl, or any combination thereof; and R 3 is anhydrous, hydrogen, alkyl, a terpenoid moiety, cycloalkyl, aryl, heterocycle, alkenyl, alkynyl, or any combination thereof. Fig.11 In, R 4 and R 5are each independently methyl, CF3, perhaloalkyl, aryl, benzyl, 2,2-disubstituted C3-C 20 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 R 6 Methyl, CF3, perhaloalkyl, 2,2-disubstituted C3-C 20 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, a terpenoid moiety, a cycloalkyl, an aryl, a phenyl, a benzyl, a heterocycle, a conjugated alkyl, a 1-alkenyl, a 1-alkynyl, a 2-alkenyl, a 2-alkynyl, or any combination thereof.

[0632] In another embodiment, the same trialkoxysilane linker molecule (trialkoxysilane linker molecule in FIGS. 12-13 ) is initially used, however at a higher concentration (>10% by wt), and it is initially self-polymerized under basic catalysis (for standard particles and thermally stabilized particles, respectively). Fig. 12A and Fig.13A Functionalization of the solid-supported linker proceeds analogously to the procedure described above for particles comprising one monomer unit per antimicrobially active unit ( Figure 4-Figure 9 ).

[0633] In some embodiments, Fig.10 - The core in the process of Figure 13 already includes (at least one) polymerizable unit covalently linked / bonded thereto (directly or indirectly via a linker as described herein). Fig.10- The particles produced by the above process depicted in Figure 13 are further reacted to provide antimicrobial particles of the present invention, which antimicrobial particles include at least one antimicrobial active unit and at least one polymerizable unit. In some other embodiments, the further reactions are described in detail in the sections entitled "Solid Support Method as a Method for Preparing Antimicrobial Particles Comprising One Monomer Unit for Each Antimicrobial Active Unit" above; and "Solution Method as a Method for Preparing Antimicrobial Particles Comprising One Monomer Unit for Each Antimicrobial Active Unit".

[0634] Solution process as a method for preparing antimicrobial preparations containing more than one monomer unit per antimicrobial active unit Granular method

[0635] The solution method comprises several stages. The first step involves the elongation of the linker molecule. In another embodiment, this step is achieved synthetically via one or more steps. In another embodiment, the elongation is achieved by sequential addition of a difunctionalized alkane and a diaminoalkane, wherein the amine (of the linker and the diaminoalkane) attacks the electrophilic center of the difunctionalized alkane (of the standard particle and the particle with enhanced thermal stability, respectively). Fig.14 and Fig.15 : Step 1 and Step 2). In another embodiment, such sequential addition is optionally repeated for 1-10 times. In the second stage, the antimicrobial active group (usually attached to an alkylene chain) is grafted to the resulting extended linker. In another embodiment, the grafting is completed when the amine on the extended linker attacks the acyl halide portion of the molecule of the grafted antimicrobial active group ( Fig.14 and Fig.15 , step 3). Finally, the extended antimicrobial active linker is attached to the core via its functionalization. In this step, the linker molecules (a few percent dilute solution) are allowed to condense onto the particle surface via (acid-catalyzed) hydrolysis of the leaving group (surface functionalization), resulting in the attachment of the linker to the core ( Fig.14 and Fig.15 , step 4).

[0636] For silica standard particles functionalized with dimethylethylammonium, the process Figure 16-Figure 17 Similarly, for silica particles functionalized with dimethylbenzylammonium having enhanced thermal stability, the process Figure 18-Figure 19 exemplified in , but are applicable to other hydroxyl terminated cores and antimicrobially active groups. Figure 14-Figure 19 The process is applicable to other hydroxyl terminated cores and antimicrobial active groups.

[0637] In another embodiment, the same trialkoxysilane linker molecule is initially used, however at a higher concentration (>10% by weight), and it is initially self-polymerized under basic catalysis (see, e.g., for standard particles and thermally stabilized particles, respectively). Fig. 12B and Fig. 13B Functionalization of the linker proceeds analogously to the procedure described above for particles comprising one monomer unit per antimicrobially active moiety (see, e.g., Figure 4-Figure 9 ).

[0638] In some embodiments, Figure 14-Figure 19 In another embodiment, the core of the process of already includes (directly or indirectly via a linker as described herein) covalently connected / bonded to it (at least one) polymerizable unit. Figure 14-Figure 19 The particles produced by the above process described in further react to provide the antimicrobial particles of the present invention, the antimicrobial particles comprising at least one antimicrobial active unit and at least one polymerizable unit. In some other embodiments, the further reactions are described in detail in the sections entitled "Solid Support Method as a Method for Preparing Antimicrobial Particles Comprising One Monomer Unit for Each Antimicrobial Active Unit" above; and "Solution Method as a Method for Preparing Antimicrobial Particles Comprising One Monomer Unit for Each Antimicrobial Active Unit".

[0639] In some embodiments, when it is noted herein that Figure 4-Figure 19 The core in the process of already includes (at least one) polymerizable unit covalently linked / bonded to it (directly or indirectly via a linker as described herein), which means that the polymerizable unit is linked / bonded to the core via any of the methods as described above, for example, as in the sections entitled "Solid Support Method as a Method for Preparing Antimicrobial Particles Comprising One Monomer Unit for Each Antimicrobial Active Unit"; and "Solution Method as a Method for Preparing Antimicrobial Particles Comprising One Monomer Unit for Each Antimicrobial Active Unit".

[0640] In one embodiment, the antimicrobial particle is prepared according to any of the processes as described above (having one or more monomer units per antimicrobial unit), wherein the actual polymerizable functional group comprises more than one functional polymerizable group; see Z3 of formula (7). In another embodiment, a process similar to the process described above is provided to produce the antimicrobial particle, the antimicrobial particle having Z3 comprising more than one functional polymerizable group; Z3 is attached as described above (wherein Z3 is a "monofunctional" polymerizable group).

[0641] Preparation of core particles

[0642] In some embodiments, particles of the composite material of the invention comprising one or more monomer units of each antimicrobially active moiety comprise a core prepared as follows.

[0643] Porous silica materials can be prepared by reaction of SiCl4 with alcohol or water, followed by centrifugation and / or heating with gas flow or drying under vacuum.Dense fumed silica particles (pyrogenic) are prepared by pyrolysis of SiCl4.

[0644] An alternative preparation method for the silica core material can be carried out by hydrolyzing tetraethyl orthosilicate (TEOS) or tetramethyl orthosilicate (TMS) in the presence of alcohol or aqueous solution and under alkaline (Stober) or acidic catalytic conditions.

[0645] Mesoporous silica particles can be prepared by hydrolyzing TEOS or TMS at low temperatures, for example, at temperatures not exceeding 60° C., followed by dehydration by centrifugation and / or evaporation under air flow or vacuum conditions.

[0646] Dense particles can be produced using intense heating in a process known as calcining. Typically, such a process occurs at high temperatures of about 250°C.

[0647] In some embodiments, the core is POSS, and the POSS does not require any further functionalization; rather, the core already includes the antimicrobially active units and polymerizable units attached thereto (via the siloxane moieties).

[0648] In one embodiment, the present invention provides an antimicrobial particle comprising POSS as a core, antimicrobially active units attached to the POSS core via siloxane units of the POSS, and polymerizable units.

[0649] In one embodiment, the present invention provides a method for preparing an antimicrobial POSS, the method comprising:

[0650] - Optionally, alkylating the antimicrobial silicone precursor with an alkylating agent to form a quaternary ammonium, a tertiary amine, or any combination thereof;

[0651] - mixing an optionally alkylated antimicrobial siloxane precursor with a polymerizable siloxane precursor;

[0652] - hydrolyzing the siloxane precursor to form an antimicrobial POSS; and

[0653] -Providing post-treatment conditions to obtain antimicrobial POSS particles.

[0654] In some embodiments, the antimicrobial siloxane precursor is formula (IC) as described above. In one embodiment, the antimicrobial siloxane precursor is an alkyl-trialkoxysilane, a trialkoxyarylsilane, a trihaloalkylsilane, or a trihaloarylsilane, wherein the alkyl or aryl group is end-capped 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).

[0655] In some embodiments, the polymerizable precursor is an alkyl-trialkoxysilane, a trialkoxyarylsilane, a trihaloalkylsilane, or a trihaloarylsilane, wherein the alkyl or aryl group is end-capped with Z3 of formula (7) as described above. In one embodiment, the polymerizable precursor is 3-(trimethoxysilyl)propyl acrylate.

[0656] 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 first performed with a first alkylating agent and then performed with a second alkylating agent at the second stage. In another embodiment, alkylation is first performed with 1-iodooctane and then performed with iodomethane at the second stage.

[0657] In some embodiments, the hydrolysis is acidic or alkaline. In one embodiment, the hydrolysis is alkaline. In one embodiment, the hydrolysis is acidic. In one embodiment, the hydrolysis is alkaline and is carried out using any suitable base in the art (e.g., NaHCO 3 , NaOH, Na 2 CO 3 ). In one embodiment, the hydrolysis is acidic and is carried out using any suitable acid in the art (e.g., HCl, HOAc, CF 3 CO 2 H).

[0658] In some embodiments, post-treatment conditions may include any suitable technique as known in the art. In one embodiment, post-treatment includes freeze drying and then mechanically powdering the particles to provide dry antimicrobial POSS particles.

[0659] In some embodiments, the present invention provides antimicrobial POSS particles prepared according to any of the above methods.

[0660] In some embodiments, provided herein is an antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein each silicon atom of the POSS is functionalized by at least one quaternary ammonium group or by at least one functional polymerizable group; and wherein the molar ratio of silicon atoms functionalized by at least one quaternary ammonium group to silicon atoms functionalized by at least one functional polymerizable group is between 10:1 and 1:10, respectively. In one embodiment, the POSS antimicrobial particle comprises an antimicrobially active unit and a polymerizable unit attached to the POSS core via a siloxane unit of the POSS.

[0661] In other embodiments, methods for preparing the antimicrobial particles provided herein include:

[0662] mixing a first monomer unit comprising a trialkoxysilane linked to a quaternary ammonium group via a linker and a second monomer unit comprising a trialkoxysilane linked to a functional polymerizable group via a linker, respectively, in a ratio between 10:1 and 1:10; and

[0663] The first monomer unit and the second monomer unit are hydrolyzed in alkaline conditions to polymerize and form a POSS core that is functionalized with an antimicrobial group and a functional polymerizable group.

[0664] 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 alkaline. In other embodiments, the N-alkylation of AEAPTS comprises alkylation with 1-iodooctane followed by alkylation with iodomethane.

[0665] Preparation of the composition of the present invention

[0666] In some embodiments, the composite material of the present invention is prepared by embedding antimicrobial particles into a polymer material of the present invention. In another embodiment, one type of particle is embedded in a polymer material. In another embodiment, a combination of different particle types is embedded in a polymer material. In some embodiments, embedding can be achieved by a variety of methods.

[0667] In some embodiments, functionalized microparticles are embedded in polymeric materials by two methods: A) extrusion technology: the particles are added to a molten thermoplastic polymer into an extruder, such as a twin-coned extruder. B) a thermoplastic polymer or a 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 as used for the polymer, and the mixture is added to the dissolved polymer using an overhead stirrer or homogenizer. After the particles are fully dispersed in the polymer, the solution is evaporated using conventional distillation or evaporation methods.

[0668] In some embodiments, embedding functionalized microparticles into silicone-based polymer materials is achieved by several methods: A) Achieving room temperature vulcanization (RTV) of silicone precursors, where the particles are incorporated into unpolymerized or pre-polymerized silicone prior to final curing at a final concentration of 0.5% wt.-8% wt. particles / silicone polymer. In another embodiment, the cure is activated by moisture. In another embodiment, the cure is activated by heat. B) Achieving RTV of silicone precursors, where polymerization is induced by mixing the two components of the polymerization mixture. In another embodiment, the particles are incorporated into two parts at a final concentration of 0.5% wt.-8% wt. particles / silicone polymer, or into one part at double the concentration, giving a final concentration of 0.5% wt.-8% wt. particles / silicone polymer.

[0669] Thus, according to some embodiments, the present invention provides a method for preparing a composition, the method comprising embedding a plurality of antimicrobial particles in a polymer material as described above, wherein the particles are embedded in the material, the method comprising the steps of adding the particles as described above to a molten polymer material using extrusion, or to a polymer solution in a solvent, or via polymerization of the particles and polymer precursors. In one embodiment, the same substituents (e.g., R1, R2, R3, etc.) within the particles present in "more than one particle" have the same ranges as indicated above in all of the particles; however, for the same substituent, the specific meaning in each of the particles may be different; for example, in "Particle #1" R1 = methyl, and in "Particle #2" R1 = propyl, so at least due to this point and in this specific embodiment, particles 1-2 are different.

[0670] In some embodiments, the particles according to the present invention are uniformly distributed on the outer surface of the polymer material with a surface concentration between about 0.1 and about 100 particles per square micron. In another embodiment, the particles according to the present invention are uniformly distributed on the outer surface of the polymer material with a surface concentration between about 1 and about 100 particles per square micron. The term "uniform distribution" is used to represent a distribution characterized by a standard deviation of the number of particles per square micron that does not exceed the average number of particles per square micron. Uniform distribution can be advantageous for reproducibility and product specifications. If the distribution is not uniform, the product may exhibit different properties in different areas. The distribution of particles away from the outer surface, i.e., their bulk concentration, can be similar to the distribution of particles on the outer surface. As a general rule, the total surface of the particles can account for up to about 20% of the surface of the material, for example, the total surface of the particles can account for between 1% and 15% of the surface of the material, or between 1% and 5% or 1% and 3% of the surface of the material in some embodiments.

[0671] According to some embodiments, there is an average of at least one particle of the present invention per square micrometer of the outer surface of the polymeric material.

[0672] Compositions and methods of use thereof

[0673] According to another aspect of the present invention, there is provided a method for inhibiting bacteria by contacting bacteria with the antimicrobial particles of the present invention or a composition or pharmaceutical composition comprising one or more particles of the present invention. The term "inhibition" may refer to any of the following: destruction of bacteria, such as annihilation 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 bacterial colonies; prevention of bacterial growth; irreparable damage to bacteria; destruction of such bacterial biofilms; induction of short-term or long-term damage to some or all of the existing biofilms; prevention of the formation of such biofilms; induction of biofilm management; or causing any other type of consequence that may affect such colonies or biofilms and cause immediate or long-term damage (partial or total) to them.

[0674] The term "biofilm" refers to a population of biological species (bacteria) attached to a solid surface.

[0675] In some embodiments, inhibition is achieved by contacting the bacteria with a matrix comprising up to 5% w / w, or such as up to 1%, of particles according to the invention, or a composition comprising the same.

[0676] In one embodiment, the present invention also provides a composition or pharmaceutical composition comprising the antimicrobial particles as mentioned above. In another embodiment, the composition / pharmaceutical composition comprises one type of particles. In another embodiment, the composition / pharmaceutical composition comprises a combination of different particle types. In one embodiment, non-limiting examples of compositions / pharmaceutical compositions of the present invention are dental adhesives, bone cements, dental restorative materials such as all types of composite-based materials for filling tooth decay cavities, endodontic filling materials (cementities and fillings) for filling root canal spaces in root canal treatments, materials for temporary and final tooth restoration or tooth replacement, including but not limited to inlays, onlays, crowns, partial dentures (fixed or removable), dental implants, and permanent and temporary cements used in dentistry for a variety of known purposes, dental and orthopedic resin-based cements, sealants, composites, adhesives and bonding agents, dental restorative composites, bone cements, toothpastes, lotions, hand disinfectants, ointments and creams for dermatology, wound care or the cosmetic industry, plastic wear for medical and research laboratories; food packaging primarily for dairy products and fresh meat and fish; pharmaceutical packaging; coatings for ships to prevent the growth of biofilms or to treat, destroy and / or kill biofilms or bacteria therein, coatings for bathrooms, coatings for hospitals and clean rooms; water filtration media and many others. Each possibility represents a separate embodiment of the present invention. In some embodiments, the particles or compositions comprising the same are used in dental and orthopedic resin-based binders, sealants, composites, adhesives and adhesives; in dental and orthopedic metal implants and wires; in surgical sutures; in catheters, metal surgical tools, non-surgical medical devices. Each possibility represents a separate embodiment of the present invention.

[0677] In one embodiment, the composition or composite material of the present invention is a varnish or glaze applied to a tooth surface, a restoration of a tooth, or a crown containing the particles of the present invention. In another embodiment, the varnish or glaze provides a protective coating paint; a polished appearance on the surface of a tooth surface, a restoration of a tooth, or a crown. In another embodiment, the varnish is a fluoride varnish, which is a highly concentrated form of fluoride that is applied to the surface of the tooth as a type of topical fluoride therapy. In another embodiment, the purpose of glazing is to seal the open pores in the surface of fired porcelain. Dental glazes include colorless glass powders that are applied to the surface of fired crowns to produce a smooth surface. Unglazed or trimmed porcelain can also cause inflammation of the soft tissues it contacts.

[0678] In one embodiment, the composition / pharmaceutical composition of the present invention is in the form of a group selected from, for example, creams, ointments, pastes, dressings and gels, wherein the composition is formulated for topical application or local administration. In another embodiment, the composition is intended for application to the oral cavity. The composition can be formulated as a toothpaste, and / or can be applied to a surface or medical device selected from the group consisting of: denture cleaners, dressings or gels after sanitization, mucosal adhesive pastes, dental adhesives, materials based on dental restoration composites for filling teeth, caries, dental restoration endodontic filling materials for filling root canal spaces in root canal treatment, dental restoration materials for temporary and final tooth restoration or tooth replacement, dental inlays, dental onlays, crowns, partial dentures, complete dentures, dental implants and dental implant abutments.

[0679] In one embodiment, the pharmaceutical composition further comprises at least one pharmaceutically active ingredient. In another embodiment, non-limiting examples of pharmaceutically active ingredients include analgesics, antibiotics, anticoagulants, antidepressants, anticancer agents, antiepileptics, antipsychotics, antivirals, sedatives, and antidiabetics. In another embodiment, non-limiting examples of analgesics include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), morphine, and oxycodone. In another embodiment, non-limiting examples of antibiotics include penicillins, 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 anticancer agents include capecitabine, mitomycin, etoposide, and pembrolizumab. In another embodiment, non-limiting examples of antiepileptics include acetazolamide, clobazam, ethosuximide, and lacosamide. In another embodiment, non-limiting examples of antipsychotics include risperidone, ziprasidone, paliperidone, and lurasidone. In another embodiment, non-limiting examples of antivirals include amantadine, rimantadine, oseltamivir, and zanamivir. In another embodiment, non-limiting examples of sedatives include alprazolam, clorazepate, diazepam, and estazolam. In another embodiment, non-limiting examples of antidiabetic agents include glimepiride, gliclazide, glyburide, and glipizide.

[0680] In another embodiment, the pharmaceutical composition also includes an excipient. In another embodiment, the excipient includes a binder, a coating, a lubricant, a flavoring agent, a preservative, a sweetener, a vehicle, and a disintegrant. In another embodiment, the non-limiting examples of binders include carbohydrates, gelatin, polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG). In another embodiment, the non-limiting examples of coatings include hydroxypropyl methylcellulose, polysaccharides and gelatin. In another embodiment, the non-limiting examples of lubricants include talc, glyceryl stearate, silicon dioxide and magnesium stearate. In another embodiment, the non-limiting examples of disintegrants include cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose (croscarmellose sodium)) and modified starch sodium glycolate.

[0681] In one embodiment, the present invention relates to a packaging composition comprising a thermoplastic polymer and / or hydrogel embedded with antimicrobial particles as mentioned 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 of food, beverages, pharmaceutical ingredients, medical devices, pre-operative surgical equipment, pre-operative equipment, cosmetics and sterilized equipment / sterilized materials.

[0682] In one embodiment, the packaging composition comprises a thermoplastic polymer and / or hydrogel embedded with particles as mentioned above. 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 polymethyl methacrylate or polyurethane.

[0683] In another embodiment, the packaging composition also includes a binder, a coating, a lubricant and a disintegrant. In another embodiment, the non-limiting examples of binders include saccharides, gelatin, polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG). In another embodiment, the non-limiting examples of coatings include hydroxypropyl methylcellulose, polysaccharides and gelatin. In another embodiment, the non-limiting examples of lubricants include talc, glyceryl stearate, silicon dioxide and magnesium stearate. In another embodiment, the non-limiting examples of disintegrants include cross-linked polyvinyl pyrrolidone, cross-linked sodium carboxymethyl cellulose (croscarmellose sodium) and modified starch sodium glycolate.

[0684] In one embodiment, the packaging composition is used to package a pharmaceutical ingredient. In another embodiment, non-limiting examples of pharmaceutical ingredients include analgesics, antibiotics, anticoagulants, antidepressants, anticancer agents, antiepileptics, antipsychotics, antivirals, sedatives, and antidiabetics. In another embodiment, non-limiting examples of analgesics include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), morphine, and oxycodone. In another embodiment, non-limiting examples of antibiotics include penicillins, 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 anticancer agents include capecitabine, mitomycin, etoposide, and pembrolizumab. In another embodiment, non-limiting examples of antiepileptics include acetazolamide, clobazam, ethosuximide, and lacosamide. In another embodiment, non-limiting examples of antipsychotics include risperidone, ziprasidone, paliperidone, and lurasidone. In another embodiment, non-limiting examples of antivirals include amantadine, rimantadine, oseltamivir, and zanamivir. In another embodiment, non-limiting examples of sedatives include alprazolam, clorazepate, diazepam, and estazolam. In another embodiment, non-limiting examples of antidiabetic agents include glimepiride, gliclazide, glyburide, and glipizide.

[0685] In one embodiment, the packaging composition is used for the packaging of food ingredients. In another embodiment, non-limiting examples of food ingredients packaged with the packaging material of the present invention include fresh food, preservatives, sweeteners, color additives, flavorings and spices, nutrients, emulsifiers, adhesives and thickeners. In another embodiment, non-limiting examples of fresh food 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 isoascorbate, 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, β-carotene, grape skin extract, cochineal extract or carmine and capsicum oleoresin. In another embodiment, non-limiting examples of flavorings and spices include monosodium glutamate, glycinate, inosinic acid, isopentyl acetate and limonene and allyl caproate. In another embodiment, non-limiting examples of nutrients include thiamine hydrochloride, riboflavin (vitamin B2), nicotinic acid, nicotinamide, folic acid (folate) or folic acid (folic acid). In another embodiment, non-limiting examples of emulsifiers include soy lecithin, monoglycerides 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.

[0686] In one embodiment, the invention provides a method for inhibiting or preventing biofilm formation, the method comprising applying a composition of the invention to a susceptible or infected surface or medical device.

[0687] In another embodiment, the present invention provides a composition of the present invention for use in inhibiting or preventing biofilm formation.

[0688] In one embodiment, the present invention provides a method for inhibiting or preventing biofilm formation or growth, the method comprising placing a medical device of the present invention (comprising a composition of the present invention as mentioned above) on a surface to be treated. In another embodiment, the medical device is a wound dressing.

[0689] In another embodiment, the present invention provides a medical device of the present invention for use in inhibiting or preventing biofilm formation or growth.

[0690] In one embodiment, the present invention provides a method for inhibiting bacteria, comprising the step of contacting the bacteria with the pharmaceutical composition or packaging composition or composite material of the present invention.

[0691] In another embodiment, the present invention provides a pharmaceutical composition or packaged composition for inhibiting bacteria.

[0692] In one embodiment, the present invention provides a method for treating, decomposing or killing biofilms or bacteria therein, the method comprising applying the pharmaceutical composition or packaging composition or composite material of the present invention to a susceptible or infected surface or medical device.

[0693] In another embodiment, the present invention provides a composite material or a pharmaceutical composition or a packaging composition of the present invention for treating, decomposing or killing a biofilm or bacteria therein.

[0694] Applications outside the medical field can be, for example, in clothing (e.g., for sports or outdoor activities; to prevent bacteria-induced sweat odor), the interior of sports shoes or shoes where bacteria tend to accumulate, 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 items.

[0695] In some embodiments, the antimicrobial compositions or composites of the present invention achieve annihilation of at least about 99% of contacted bacteria, or in some embodiments, at least about 99.9% or 99.99% of contacted bacteria.

[0696] It has also been surprisingly found that the particles within the compositions / composites / medical devices of the present invention retain high antimicrobial properties over time without leaching and without changing the properties of the host matrix. Such particles exhibit enhanced antibacterial activity that originates from the presence of tightly packed antibacterial groups on the surface of a given particle.

[0697] Medical device of the present invention

[0698] In one embodiment, the present invention also 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, joint replacements, 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, ocular prostheses, urethral stents (urethral stents), coatings for subcutaneous (such as plastic surgery or dental) implants, insulin pumps, contraceptive devices, pacemakers, tubes and cannulas for intravenous infusions, tubes and cannulas for dialysis, surgical drains, urinary catheters, endotracheal tubes, wound covering (dressings and adhesive bandages) and treatment (e.g., gels, ointments, pastes and creams for wound care that reduce biofilm and bacteria to aid wound healing) materials, sutures, catheters of all kinds inserted temporarily or permanently into blood vessels and the urinary system, shunts for brain applications, surgical gloves, tips for ear examinations, sensitive statoscope ends used by medical personnel, and other components; toothbrushes, toothpicks, dental floss, interdental and tongue brushes, surgical sutures, metal surgical tools, non-surgical medical instruments, metal implants and wires for dental and plastic surgery and surgical drains, syringes, trays, tips, gloves, and other accessories used in common medical and dental procedures.

[0699] In one embodiment, the present invention also provides a medical device comprising a dental appliance. In one embodiment, the present invention also provides a medical device comprising an orthodontic appliance. Dental appliances and orthodontic appliances include particles and compositions of the present invention. In some embodiments, orthodontic appliances include aligners, brackets, dental attachments, bracket auxiliary devices, ligature ties, pins, bracket slot caps, wires, screws, micro-nails, adhesives for brackets and attachments, and other orthodontic appliances, dentures, partial dentures, dental implants, periodontal probes, periodontal chips, membranes, or spacers between teeth for accelerating tooth alignment. In some embodiments, dental appliances may include mouth guards, night guards, oral devices for treating / preventing sleep apnea, and mouth guards for sports activities for preventing tooth grinding (bruxer, bruxism).

[0700] In one embodiment, the present invention also provides percutaneous medical devices such as orthopedic external fixation screws and wires for bone fixation and stabilization, and transmucosal elements for dental implants such as healing caps, abutments (such as multiunit), for screw-retained dentures or for adhesive-retained dentures.

[0701] In one embodiment, the present invention also provides medical devices, which include endoscopes (rigid and flexible), including but not limited to colonoscopes, gastroscopes, duodenoscopes, bronchoscopes, cystoscopes, ENT scopes, laparoscopes, laryngoscopes and similar instruments used to examine or treat the interior of a patient's body, including any parts thereof, and accessories and other devices used in the procedure that come into contact with body tissues or body fluids; tubes, pumps, containers and connectors (for use inside or outside the body) through which fluids, air or gases can be pumped into or withdrawn from a patient and can become contaminated by the patient or transfer contaminants from other patients; items such as brushes, trays, covers, tubes, connectors, cabinets and bags used for reprocessing, cleaning, transporting and storing such equipment and which can transmit or host biological contaminants; and filters for air or water used in dental or medical procedures, hospital surfaces (such as floors, tabletops), drapes, curtains, linens, handles, etc.

[0702] The antimicrobial properties can protect patients and medical staff from cross contamination between patients or between patients and examiners. Self-sterilizing packaging of medications and items entering the operating room is also beneficial.

[0703] In one embodiment, the present invention also provides a process for preparing a medical device comprising a composite material. In another embodiment, the medical device is prepared by the steps of providing a fluid phase of the composite material of the present invention; shaping the fluid; and hardening the shaped fluid to provide the desired medical device. In another embodiment, the medical device is prepared by the steps of providing a solid phase of the composite material; and shaping the solid to provide the desired medical device. In another embodiment, the shaping is accomplished via extrusion or molding. In another embodiment, the fluid phase of the composite material comprises a molten composite material or a composite material dissolved in a solvent.

[0704] Another polymer material used in the context of the present invention is a resin used in dental, surgical, surgical and plastic surgery composites. In such applications, the antimicrobial particles can be first dispersed in the resin portion, or added simultaneously with fillers or any other solid ingredients (if any). Most of these resins are acrylic or epoxy type monomers that undergo polymerization in vivo.

[0705] In some embodiments, the terms "antimicrobial" and "antibacterial" are used interchangeably herein.

[0706] The following examples are presented in order to more fully illustrate the preferred embodiments of the invention. However, they should in no way be construed as limiting the broad scope of the invention. Example

[0707] Example 1

[0708] Preparation of QASi-PF particles (without acrylate)

[0709] [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 into hydrophobic quaternary ammonium groups. Subsequently, the silane groups were hydrolyzed in aqueous NaHCO solution and then condensed to form POSS particles.

[0710] Dry POSS particles were obtained by freeze drying and then mechanical powdering.

[0711] Example 2

[0712] Preparation of QASi-PA particles (with acrylate)

[0713] [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 into hydrophobic quaternary ammonium groups. 3-(Trimethoxysilyl)propyl acrylate (0.25 eq) was added to the solution. Subsequently, the silane groups were hydrolyzed in aqueous NaHCO3 solution, followed by condensation and formation of POSS particles. Dry POSS particles were obtained by freeze drying and then mechanical powdering.

[0714] Example 3

[0715] Preparation of dental composites

[0716] Resin preparation:

[0717] 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.

[0718] Composite material kneading:

[0719] To the prepared resin, glass powder was added to give a ratio of 78.5% filler and 20% resin and 1.5% QASi particles (Example 1 or Example 2). The composite material was mixed under vacuum using a planetary kneader until a homogeneous paste was obtained.

[0720] Example 4

[0721] Leaching Testing of Granules – Validation

[0722] The following validation was performed for the limit of detection test of QASi on polar and non-polar extracts. During the study, specificity and detection limits were validated using the sample preparation and biological evaluation guidelines of ISO 10993-12 and ISO 10993-18. An HPLC / MS (High Performance Liquid Chromatography Mass Spectrometry) system (Agilent 1260HPLC coupled with LC / MS Triple Quad) was used, with which the analytical method for quantification of the analytes was developed, and standard laboratory equipment and reagents (water, acetonitrile, formic acid, ethanol and NaCl 0.9%) were used.

[0723] A 500 μg / ml QASi-PF MS1 standard solution was prepared using approximately 12.5 mg of particles dissolved and diluted to 25 ml with ethanol; and diluted as shown in the table below.

[0724]

[0725] A 500 μg / ml QASi-PA MS2 standard solution was prepared using approximately 12.5 mg of particles dissolved and diluted to 25 ml with ethanol; and diluted as shown in the table below.

[0726]

[0727] A preliminary scan was performed in ESI+ mode from m / z 100 to m / z 1000 to find the precursor ions for each reference. The ion signal of QASi-PF was found to be 266.3 m / z, and the ion signal of QASi-PA was found to be 273.2 m / z. The following conditions were used to test the samples, and under these conditions, 1 μg / ml samples were detected in both solvents and without interfering signals.

[0728]

[0729] From this, it was concluded that the method was able to assess the presence of substances at 266.3 and 273.2 that were not present on the solvent blank in order to verify the presence of QASi leached from the extraction device.

[0730] Example 5

[0731] Leaching tests of QASi-PF particles and QASi-PA particles (Example 1 and Example 2, respectively) in dental composites (composites for cavity filling and tooth restoration)

[0732] Granules were prepared as in Examples 1 and 2, compositions were prepared as in Example 3, and leachability tests were performed as in Example 4. The following solutions and concentrations were used.

[0733]

[0734] The low leachability of QASi-PA particles (with acrylate) was demonstrated compared to QASi-PF particles (without acrylate) which were more easily removed from the matrix, as exemplified below.

[0735] The results for QASi-PA particles (with acrylates) for both types of solutions are as follows, concluding that the extraction of QASi-PA in ethanol:water at 120 hours and in saline solution at 96 hours should be considered as limiting extraction. Under limiting extraction conditions, a total of 268.2 μg / g of QASi-PA was leached by ethanol:water, while no QASi-PA was leached by the saline solution. Thus, QASi-PA particles (with acrylates) were shown to have low leachability from the matrix.

[0736] QASi-PA Results:

[0737] EtOH:water (50:50)

[0738]

[0739] NaCl 0.9%

[0740]

[0741] QASi-PF results (control):

[0742] For both extraction solvents, the extraction of QASi-PF should be considered as extreme extraction at 96 hours. Under extreme extraction conditions, a total of 1454.4 μg / g of QASi-PF was leached by ethanol:water, while no QASi-PF was leached by the saline solution.

[0743] EtOH:water (50:50)

[0744]

[0745] NaCl 0.9%

[0746]

[0747] Thus, the leaching in particles without the presence of acrylate (>1400 mg / g) is more significant than the corresponding value in particles containing acrylate (268.2 mg / g).

[0748] Example 6

[0749] QASi-PA particles (Example 2) in Bond (a dental material for direct and indirect fixation of tooth restorations)

[0750] Leaching test in adhesive

[0751] According to ISO10993-12 guidelines, after limiting extraction with NaCl 0.9% and water: ethanol 50:50 solution, a leachability test as provided in Example 4 was performed to detect QASi on the test items. A solvent ratio of 0.2 g / ml was used, and the disc of the bonding material was completely immersed in the extraction solvent. Two solvents were used: NaCl 0.9% and water / ethanol (50 / 50), and the samples were stored in the following conditions: (i) at 50±2°C for 72±2 hours, (ii) at 50±2°C for 96±2 hours, and (iii) at 50±2°C for 120±2 hours (only tested when limiting was not reached at 96 hours). Each amount of each mixture was placed under the same conditions as the sample to be used as a blank. The solutions used were: a 500 μg / ml MS1 standard solution comprising approximately 12.5 mg QASi-PA dissolved in ethanol and diluted to 25 ml; a 20 μg / ml MS2 standard solution (ethanol:water 50:50) comprising 0.2 ml MS1 diluted to 5 ml with ethanol:water 50:50; and a 20 μg / ml MS2 standard solution (NaCl 0.9%) comprising 0.2 ml MS1 diluted to 5 ml with NaCl 0.9%.

[0752]

[0753] Sample preparation - Inject the samples without any further treatment and after dilution if necessary. For a 1:100 dilution, dilute 0.1 ml of each extraction solution to 10 ml with the same extraction solvent. For a 1:10 dilution, dilute 0.1 ml of each extraction solution to 1 ml with the same extraction solvent. The leachability test setup was as in Example 4.

[0754] The results are shown in the table below. The extraction of QASi-PA at 96 hours in ethanol:water and at 120 hours in saline solution should be considered as limiting extraction.

[0755] Under extreme extraction conditions, a total of 436.5 μg / g of QASi-PA was leached by ethanol:water, and 66.8 μg / g of QASi-PA was leached by the saline solution.

[0756] EtOH: Water (50:50)

[0757]

[0758] NaCl 0.9%

[0759]

[0760] Example 7

[0761] Preparation of QASi-PV particles (with silicone rubber)

[0762] [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 into hydrophobic quaternary ammonium groups. Vinyltrimethoxysilane (0.25 eq) was added to the solution. Subsequently, the silane groups were hydrolyzed in aqueous NaHCO3 solution, followed by condensation and formation of POSS particles. Dry POSS particles were obtained by freeze drying and then mechanical powdering.

[0763] Preparation of silicone rubber

[0764] Composite compounding: Pt catalyst silicone rubber was prepared by mixing unpolymerized silicone with 2% wt / wt QASi-PV and then curing at 80°C for 2 hours.

[0765] A control sample with 2% wt / wt QASi-PF was prepared simultaneously under the same conditions.

[0766] Leachability Studies

[0767] A 10 gram sample of each silicone (test and control) was immersed in 25 ml of saline and kept at 37°C for 72 hours. The liquid was then collected and examined using a UV spectrophotometer. In order to determine the correlation between the UV absorbance intensity and the QASi concentration in the liquid, a calibration curve of standard concentrations in saline was prepared and tested using the same UV spectrophotometer.

[0768] The results are QASi-PV concentration in saline after 72 hours: 0 mg per 10 grams of silicone sample - indicating that the particles remain in the silicone matrix. This is in contrast to the QASi-PF (control) concentration after 72 hours in saline: 25 mg per 10 grams of silicone sample - indicating leaching of the control particles (without vinyl groups).

[0769] Example 8

[0770] Preparation of QASi-PE particles (with epoxy)

[0771] [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 into hydrophobic quaternary ammonium groups. (3-glycidyloxypropyl)trimethoxysilane (0.25 eq) was added to the solution. Subsequently, the silane groups were hydrolyzed in aqueous NaHCO3 solution, followed by condensation and formation of POSS particles. Dry POSS particles were obtained by freeze drying and then mechanical powdering.

[0772] Preparation of epoxy resin samples

[0773] Composite kneading: Bisphenol-A diglycidyl ether (DGEBA) resin was mixed with diethylenediamine crosslinker (DETA) in a ratio of 5:1 and QASi-PE particles were added to adjust the total to 2% wt / wt and mixed using an overhead stirrer. The sample was allowed to polymerize at 37°C for 24h.

[0774] A control sample with 2% wt / wt QASi-PF was prepared simultaneously under the same conditions.

[0775] Leachability Studies

[0776] A 12 gram sample of each silicone (test and control) was immersed in 25 ml of saline and kept at 37°C for 72 hours. The liquid was then collected and examined using a UV spectrophotometer. In order to determine the correlation between the UV absorbance intensity and the QASi concentration in the liquid, a calibration curve of standard concentrations in saline was prepared and tested using the same UV spectrophotometer.

[0777] The results were that the QASi-PE concentration in the brine after 72 hours was 25 mg per 12 grams of silicone sample, indicating that most of the particles remained in the silicone matrix, which contrasted with the QASi-PF (control) concentration after 72 hours in brine: 250 mg per 12 grams of silicone sample - indicating leaching of the control particles (without epoxy groups).

[0778] Although certain features of the present invention have been illustrated and described herein, many modifications, substitutions, changes and equivalents will now occur to those skilled in the art. It should be understood, therefore, that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the invention.

Claims

1. An antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein the silicon atoms of the POSS are functionalized by at least one antimicrobial group and by at least one functional polymerizable group, wherein the at least one functional polymerizable group comprises an acrylate group, an epoxy group, a vinyl group or an isocyanate group; 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 between 10:1 and 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. The antimicrobial particle of claim 2, wherein at least one quaternary ammonium group is an N-alkylated 3-(2-aminoethylamino)propyl group, wherein the propyl terminal group is attached to a silicon atom.

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

5. The antimicrobial particle of claim 1, wherein the acrylate is propyl acrylate, wherein the propyl end groups are attached to silicon chains.

6. The antimicrobial particle of any one of claims 1-5, wherein the molar ratio is between 4:1 and 1:

1.

7. The antimicrobial particle of any one of claims 1-5, wherein the molar ratio is 4:

1.

8. The antimicrobial particle according to any one of claims 2 to 7, wherein the quaternary ammonium comprises a C1-C18 alkyl unit.

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

10. The antimicrobial particle of claim 1, wherein the antimicrobial particle is 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 alkaline.

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

13. The antimicrobial particle of any one of claims 1-12, 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 3-glycidyloxypropyl group or an unsubstituted 3-glycidyloxypropyl group.

15. The antimicrobial particle of any one of claims 1-14, wherein the at least one functional polymerizable group comprises a vinyl group.

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

17. The antimicrobial particle of any one of claims 1-16, wherein up to 70% of the silicon atoms of the POSS are capped.

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

19. A composition comprising more than one antimicrobial particle according to any one of claims 1 to 16 and a polymer material as a matrix.

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

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

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

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

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

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

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

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

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

30. The composition of claim 19, wherein the composition comprises a mixture of different antimicrobial particles.

31. The composition of any one of claims 19-30, wherein up to 70% of the silicon atoms of the POSS are capped.

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

33. The composition according to any one of claims 19-32, wherein the composition is capable of filling tooth decay cavities, is a dental restorative endodontic filling material for filling root canal space in root canal treatment, or is selected from the group consisting of dental restorative materials intended for temporary and final tooth restoration or tooth replacement, dental inlays, dental onlays, crowns, partial dentures, complete dentures, dental implants, dental implant abutments, and adhesives intended for permanent bonding of crowns, bridges, onlays, partial dentures and orthodontic appliances to tooth enamel and dentin.

34. The composition of any one of claims 19-32, wherein the composition further comprises a filler.

35. A composition according to claim 34, wherein the composition comprises 78.5% w / w filler and 20% w / w resin.

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 provide a clear blend; followed by mixing in camphorquinone (CQ), benzoin methyl ether (BME), ethyl 4-(dimethylamino)benzoate (EDB), and butylated hydroxytoluene (BHT) to provide the resin.

37. An antimicrobial particle comprising a polyhedral oligomeric silsesquioxane (POSS) core, wherein the silicon atoms of the POSS are functionalized by at least one antimicrobial group and by at least one functional polymerizable group, wherein 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; and The antimicrobial active unit is represented by structure (1): in L1 is the first linker or bond; L2 is the second linker; L3 is the third linker or bond; R1 and R1' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof; R2 and R2' are each independently alkyl, terpenoid, cycloalkyl, aryl, heterocyclic, alkenyl, alkynyl or any combination thereof; R3 and R3' are each independently none, hydrogen, alkyl, a terpenoid moiety, a cycloalkyl, an aryl, a heterocycle, a conjugated alkyl, an alkenyl, an alkynyl, or any combination thereof; wherein if R3 or R3' is none, the nitrogen is uncharged; X1 and X2 are each independently a bond, an alkylene group, an alkenylene group or an alkynylene group; n1 is each independently an integer between 0 and 200; n2 are each independently an integer between 0 and 200; Where n1+n2≥1; m is an integer between 1 and 200, and the repeating units are the same or different; and concept represents a covalent bond to an organic or inorganic core; In another embodiment, the antimicrobial group is -N(R1)(R2)(R3) + 、-N(R1)(R2) + -、-N(R1')(R2')(R3') + or -N(R1')(R2') + -(all possible groups are covalently linked to X1 or X2).

38. A composition comprising more than one antimicrobial particle according to claim 37 and a polymer material as a matrix.

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