RU2793285C2 - Coated particles and their applications - Google Patents

Abstract

FIELD: dentistry.

SUBSTANCE: coated particle that binds to, attaches or connects to the surface of the oral cavity, and its use are claimed. The particle contains a substrate, which is a particle or nanoparticle derived from a copolymer of lactic and glycolic acids (PLGA), and a coating covalently associated with the substrate, which is ethyl lauroyl arginate hydrochloride. The particle may further contain an active ingredient.

EFFECT: introduction into the oral cavity of the coated particle provides a beneficial effect on the oral cavity.

4 cl, 6 tbl, 2 ex

Description

CROSS-REFERENCE TO RELATED APPLICATION

The present application claims the benefit of priority under U.S. Provisional Application No. 62/506,783, filed May 16, 2017.

DESCRIPTION OF THE INVENTION

The present invention relates to novel coated particles and their uses. More specifically, in certain embodiments, the present invention provides amino acid and/or polymer coated particles, or particles coated with other materials described herein, to bind or otherwise connect with oral surfaces to deliver active agents and/or for beneficial effects. on her.

Any of a variety of substrate particles, polymers, or other coating materials can be used to provide coated particles by applying a coating material to substrate particles in the present invention. In certain embodiments, the substrate particles comprise materials having carboxyl groups on the surface that can be used to interact with amino groups on the coating materials/polymers to form covalent bonds. In other embodiments, coated particles are obtained by adsorption of coating materials on a substrate. Examples of acceptable substrate particles include particles or nanoparticles formed from a copolymer of lactic and glycolic acids (PLGA), polylactic acid (PLA), polycyanoacrylates (PACA), polyacrylic acid, polyanhydrides, polyamides, polyorthoesters, polyarginate glycol, polyethylene glycol, polyvinyl alcohol, polyisobutyl cyanoacrylate (PIBCA). ), polyethylene oxide (PEO), polycaprolactone (PCL), cellulose, starch, chitosan, carrageenan, alginates, xanthan gum, gellan gum, pectins, combinations of two or more of these, etc. Certain commercially available particles include ISP Captivates capsules ™ (supplied by Ashland), Nanospheres 100 Acide Ascobique (supplied by Biosil Technologies, Inc.) - metric particles made from porous polymer and bioadhesive, etc.

The particles of the present invention may be of any suitable size. In certain embodiments, the substrate particles of the present invention are about 1 µm to about 750 nm in size, including about 1 µm to about 100 nanometers, about 50 µm to about 10 nanometers, and about 200 nanometers to about 750 nanometers.

In certain embodiments, the coated particles comprise PLGA-coated particles.

Examples of suitable materials and polymers for use in coating substrates to form coated particles of the present invention include materials having an amino group, such as amino acids, including, but not limited to, leucine, valine, tryptophan, methionine, arginine, combinations of two or more of them. and so on.; a linear polysaccharide with an amino group or other functional groups that provide active interaction between the nanoparticle material and oral surfaces (mucosal surfaces or enamel/dentin film coating). As a rule, such functional groups include functional groups involved in ionic interactions and/or in the formation of hydrogen bonds. Since the surface of the tooth as a whole is negatively charged, positively charged functional groups and compounds actively interact with the surface. Examples of such materials include, without limitation, chitosan, xanthan gum, combinations of two or more of these, and the like; polyvinylpyrrolidone (PVP) and its derivatives (e.g. Plasdone K29/32 and Plasdone S-630 polymers available from Ashland, USA), cetylpyridinium chloride, chlorhexidine, polyvinyl methyl ether maleic anhydride (PVM/MA) and isopropyl, ethyl or butyl copolymers ester of PVM/MA copolymers such as Gantrez, such as Gantrez S, S97, ES245, AN, MS, Gafquats such as Gafquats 440, 755N, HS-100 and HSi (free form cationic polymers) and other polyquaternies such as 7 , 22 & 37, Allantoin, Aqualon, Blanose and Bondwell (carboxymethyl cellulose (CMC) sodium salt), Wavemax (Linum Usitatissimum (flaxseed) seed extract (and) Salvia Hispanica seed extract (combination of polysaccharides from flaxseed and chia seeds with bioadhesive properties ), UV adhesives or urethane methacrylates used in dental composites (Genomer 4297, CQ, 4205, 4256), dextrans, dextrins (maltodextrin, cellodextrin, icodextrin, pyrodextrin, etc.), polydimethyldiammonium chlorides (Merquat) and other polyquaterniums ( Lubrizol) such as 5, 7SPR, 100, 550PR and S, polyquaternium-6, polyquaternium-10 with 1.5-2.2% nitrogen, polyquaternium-10 with 0.8-1.1% nitrogen, tetrahydropyrimidines (oxanthel , morantel, carbantel, febantel and pyrantel), polystyrene sulfonic acid (PSSA), methyl methacrylate, diethylaminoethyl methacrylate and combinations thereof (eg Kollicoat Smart Seal 30D); distearmonium/diethonium chloride PG-dimethicone (eg Silquat JR 4B); dimethicone PEG-8 phosphate (eg Siliphos A 100); mixtures of two or more of the above, etc.; and compositions described by formula I:

Where

R ₁ is a linear or branched, saturated or unsaturated aliphatic group having 5 to 22 carbon atoms;

R ₂ is selected from the group consisting of the free base and the corresponding salt forms of the functional groups:

–NH ₂ ;

moreover, these salt derivatives have an anion X ^- preferably selected from the group consisting of acetate, benzoate, besylate, bromide, chloride, chlorotheophyllinate, citrate, ethanesulfonate, fumarate, gluconate, hippurate, iodide, fluoride, lactate, lauryl sulfate, malate, layate, mesylate, methyl sulfate, napsilate, nitrate, octadecanoate, oxalate, pamoate, phosphate, polygalacturonate, succinate, sulfate, tartrate and tosylate;

n is 0–4; And

R ₃ is a linear or branched, saturated or unsaturated aliphatic group having 1 to 6 carbon atoms.

Compositions of formula I may have any suitable linear or branched, saturated or unsaturated aliphatic group having from 5 to 22 carbon atoms in relation to R ₁ . Examples of suitable linear or branched, saturated or unsaturated aliphatic groups having from 5 to 22 carbon atoms include linear or branched C ₅ -C ₂₂ alkyl groups such as pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl up to until proved, etc.; as well as C ₅ -C ₂₂ linear or branched alkylene groups, for example, from myristolyl to doxanehexaial, etc.

In certain embodiments, R ₁ is a straight or branched alkyl group having a carbon chain containing from 5 to 22 carbon atoms, including, for example, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl up to docasonyl. In certain embodiments, R ₁ is a linear or branched alkyl group having a carbon chain containing from 7 to 18 carbon atoms, including, for example, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl and octadecyl. In some other embodiments, R ₁ is a straight or branched alkyl group having a carbon chain containing from 9 to 14 carbon atoms, including, for example, decyl, undecyl, dodecyl up to tetradecyl. In certain embodiments, R ₁ is an undecyl group. In certain embodiments, R ₁ is a heptyl group. In certain embodiments, R ₁ is a heptadecyl group.

In certain embodiments, R ₁ is a linear or branched alkenyl group having a carbon chain containing from 5 to 22 carbon atoms, including, for example, 9-hexadecenyl, 9-octadecenyl, 11-decenyl, 9,12-octadecanedienyl, 9, 12,15-octadecatrienyl; 6,9,12-octadecatrienyl; In certain other embodiments, R ₁ is a linear or branched alkenyl group having a carbon chain containing from 16 to 20 carbon atoms, including, for example, 9-hexadecenyl, 9-octadecenyl, 11-decenyl, 9,12-octadecanedienyl, 9 ,12,15-octadecatrienyl and 6,9,12-octadecatrienyl.

In certain embodiments, R ₁ is a branched alkyl group having a carbon chain containing from 5 to 22 carbon atoms, including, for example, 2-decyldodecanyl, 2-nonyltridecanyl, 2-octyltetradecanyl, 2-heptylpentadecanyl, 2-hexylhexadecanyl, 2- pentylheptadecanil, 21-methicosanil, 18-ethylcosanil, 16-propylnadecyl and 14-butyloctadecyl.

Compositions of formula I may contain an R ₂ group which is an amino group in free base form (–NH ₂ ) or a salt thereof, or a guanidinyl functional group in free base form (–NH(CNH)NH ₂ ) or a salt thereof. Examples of suitable amine and guanidinyl salts include salts of such groups having an anion (X–) selected from the group consisting of acetate, benzoate, besylate, bromide, chloride, chlorotheophyllinate, citrate, ethanesulfonate, fumarate, gluconate, hippurate, iodide, fluoride, lactate, lauryl sulfate, malate, layate, mesylate, methyl sulfate, napsitate, nitrate, octadecanoate, oxalate, pamoate, phosphate, polygalacturonate, succinate, sulfate, tartrate and tosylate. In certain embodiments, the implementation of the composition of the present invention has a group R ₂ that is an amino group in the form of a free base (-NH ₂ ). In certain other embodiments, the composition of the present invention has an R ₂ group, which is a guanidinyl group in free base form (–NH(CNH)NH ₂ ). In certain embodiments, the composition of the present invention has an R ₂ group, which is an amine salt having an anion selected from the group consisting of acetate, benzoate, besylate, bromide, chloride, chlorotheophyllinate, citrate, ethanesulfonate, fumarate, gluconate, hippurate, iodide , fluoride, lactate, lauryl sulfate, malate, layate, mesylate, methyl sulfate, napsitate, nitrate, octadecanoate, oxalate, pamoate, phosphate, polygalacturonate, succinate, sulfate, tartrate and tosylate. In certain other embodiments, the amine salt R ₂ has an anion selected from the group consisting of acetate, benzoate, bromide, chloride, citrate, fumarate, gluconate, iodide, fluoride, lactate, malate, nitrate, oxalate, phosphate, sulfate, and in certain in other embodiments, an anion selected from the group consisting of bromide, chloride, iodide, fluoride, oxalate, and phosphate. In addition, in certain embodiments, the composition of the present invention has an R ₂ group which is a guanidinyl salt having an anion selected from the group consisting of acetate, benzoate, besylate, bromide, chloride, chlorotheophyllinate, citrate, ethanesulfonate, fumarate, gluconate, hippurate, iodide, fluoride, lactate, lauryl sulfate, malate, layate, mesylate, methyl sulfate, napsitate, nitrate, octadecanoate, oxalate, pamoate, phosphate, polygalacturonate, succinate, sulfate, tartrate and tosylate. In certain other embodiments, the guanadinyl salt R ₂ has an anion selected from the group consisting of acetate, benzoate, bromide, chloride, citrate, fumarate, gluconate, iodide, fluoride, lactate, malate, nitrate, oxalate, phosphate, sulfate, and in certain in other embodiments, an anion selected from the group consisting of bromide, chloride, iodide, fluoride, oxalate, and phosphate.

Compositions of formula I may have any suitable linear or branched, saturated or unsaturated aliphatic group having from 1 to 6 carbon atoms in relation to R ₃ . Examples of suitable linear or branched, saturated or unsaturated aliphatic groups having from 1 to 6 carbon atoms include linear or branched C ₁ -C ₆ alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, tert-pentyl, neopentyl, isopentyl, hexyl, isohexyl, neohexyl; as well as linear or branched C ₂ -C ₆ alkenyl groups such as vinyl, allyl, propenyl, butenyl, pentenyl, hexenyl, etc. In certain embodiments, R ₃ is a linear or branched alkyl group having a carbon chain containing from 1 to 4 carbon atoms, including, for example, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl and tert-butyl. In certain other embodiments, R ₃ is a straight or branched alkyl group having a carbon chain containing from 1 to 3 carbon atoms, including, for example, methyl, ethyl, propyl, and isopropyl. In certain embodiments, R ₃ is an ethyl group.

In certain embodiments, R ₃ is a linear or branched alkenyl group having a carbon chain containing from 2 to 6 carbon atoms, including, for example, vinyl, allyl, propenyl, butenyl, pentenyl, hexenyl, and the like, as well as their mixture. In certain other embodiments, R ₃ is a straight or branched alkylene group having a carbon chain containing 2 to 4 carbon atoms, including, for example, vinyl, allyl, propenyl, and butenyl.

In compounds of formula I, n can be from zero to four. In certain embodiments, n is 1 to 4, in certain embodiments, 2 to 4, in certain embodiments, 3 to 4. In certain separate embodiments, n is 0. In certain other embodiments, n is 1, in in other embodiments, n is 2, in other embodiments, n is 3, and in other embodiments, n is 4.

According to certain embodiments of the invention, the compounds of formula I are compounds in which R ₂ represents a guanidinyl functional group in the form of a free base (-NH(CNH)NH ₂ ) or a salt thereof; n is 3 or 4, preferably 3; R ₃ is an aliphatic group having a carbon chain of about 2 carbon atoms, such as an ethyl group; and R ₁ is a linear or branched, saturated or unsaturated aliphatic group, including, for example, an alkyl group having from 9 to 16 carbon atoms, including from about 10 to about 16 carbon atoms, from about 10 to about 15 carbon atoms, from about 10 to about 14 carbon atoms, about 10 to about 13 carbon atoms, about 11 to about 14 carbon atoms, about 11 to about 15 carbon atoms, about 11 to about 16 carbon atoms, and about 11 and/or about 13 carbon atoms.

In certain other embodiments, compounds of formula I are compounds in which R ₂ is a guanidinyl functional group in free base form (–NH(CNH)NH ₂ ) or a salt thereof; n is 3; R ₁ is a linear or branched, saturated or unsaturated aliphatic group including, for example, an alkyl group having about 11 carbon atoms; and R ₃ is a linear or branched, saturated or unsaturated aliphatic group, including, for example, an alkyl group having a carbon chain length of from about 1 to 11 carbon atoms, including from about 2 to about 10 carbon atoms, from about 2 to about 9 carbon atoms, about 2 to about 8 carbon atoms, about 3 to about 11 carbon atoms, about 3 to about 10 carbon atoms, about 3 to about 9 carbon atoms, about 3 to about 8 carbon atoms, and about 2 , about 6 and/or about 8 carbon atoms.

In certain other embodiments, compounds of formula I are compounds in which R ₂ is a guanidinyl functional group in free base form (–NH(CNH)NH ₂ ) or a salt thereof; n is 3; R ₁ is a linear or branched, saturated or unsaturated aliphatic group including, for example, an alkyl group having about 7 carbon atoms; and R ₃ is a linear or branched, saturated or unsaturated aliphatic group, including, for example, an alkyl group having a carbon chain length of from about 7 to 16 carbon atoms, including from about 7 to about 15 carbon atoms, from about 7 to about 14 carbon atoms, about 7 to about 13 carbon atoms, about 7 to about 12 carbon atoms, about 7 to about 11 carbon atoms, and about 7 and/or about 11 carbon atoms.

In certain other embodiments, compounds of formula I are compounds in which R ₂ is an amino group in free base form (–NH ₂ ) or a salt thereof; and n is 1, 3, or 4. Examples of such compounds include compounds in which n is 3; R ₁ is a linear or branched, saturated or unsaturated aliphatic group including, for example, an alkyl group having about 7 carbon atoms; and R ₃ is a linear or branched, saturated or unsaturated aliphatic group, including, for example, an alkyl group having a carbon chain length of from about 1 to 11 carbon atoms, including from about 2 to about 10 carbon atoms, from about 2 to about 9 carbon atoms, about 2 to about 8 carbon atoms, about 3 to about 11 carbon atoms, about 3 to about 10 carbon atoms, about 3 to about 9 carbon atoms, about 3 to about 8 carbon atoms, and about 8 and/or about 11 carbon atoms. Other examples include compositions where n is 3; R ₁ is a linear or branched, saturated or unsaturated aliphatic group including, for example, an alkyl group having about 11 carbon atoms; and R ₃ is a linear or branched, saturated or unsaturated aliphatic group, including, for example, an alkyl group having a carbon chain length of from about 1 to 11 carbon atoms, including from about 1 to about 10 carbon atoms, from about 1 to about 9 carbon atoms, about 1 to about 8 carbon atoms, about 1 to about 7 carbon atoms, about 1 to about 6 carbon atoms, about 2 to about 11 carbon atoms, about 2 to about 10 carbon atoms, about 2 to about 9 carbon atoms, about 2 to about 8 carbon atoms, about 2 to about 7 carbon atoms, about 2 to about 6 carbon atoms, and about 2 and/or about 6 carbon atoms.

One example of a compound of formula I of the present invention is [amino ({[4-dodecanamido-4-(ethylcarbamoyl)butyl]amino})methylidene]ammonium (compound 9) as shown below.

As shown in the above formula, compound 9 is a compound of formula I wherein R ₁ is an undecyl group, R ₂ is a guanidinyl group in free base form, R ₃ is an ethyl group, and n is 3.

Other examples of compounds of the present invention include, without limitation, compounds described by the following formulas.

Compound 5

Compound 8

Compound 11

Compound 6

Compound 12

Compound 7

Compound 10

Compound 13

Compound 4

Compound 3

Compound 1

Compound 2

Compound 14

Compound 15

Compound 16

Compound 17

Compound 18

Compound 19

Compound 20

Compound 21

Compound 22

Compound 23

Compound 24

Compound 25

Compound 26

Compound 31

Other examples of suitable coating materials herein include phospholipid surfactants such as PG dimonium cocamidopropyl chloride phosphate; PG-dimonium myristamidopropyl chloride phosphate; PG–dimonium lauramidopropyl chloride phosphate and mixtures thereof. In certain embodiments, the phospholipid surfactant is selected from the group consisting of cocamidopropyl PG-dimonium chloride phosphate; myristamidopropyl PG-dimonium chloride phosphate and mixtures thereof. In certain embodiments, the phospholipid surfactant is PG-dimonium myristamidopropyl chloride phosphate. Many of these materials are sold by Croda under the trade name Arlasilk™.

In certain embodiments, the implementation of the particles of the present invention may contain any of a variety of active materials to provide a beneficial effect on health. Examples of suitable actives include actives for use in the oral cavity, including, without limitation, any of a variety of actives for providing beneficial effects such as mouth cleansing, including residue removal, antimicrobial effects, including anti-plaque, anti-gingivitis, and odor reduction, biofilm disruption, prevention of bacterial adhesion, modification of the structure of the oral microbial community, modification of the metabolic profile of oral microbes, antiviral activity, anti-inflammatory properties, pH balancing, teeth whitening, stain prevention, sensitivity control, combat with caries, enamel strengthening, breath freshening, improvement of hydration/dryness of the mouth, restoration and prevention of erosion, delivery and retention of the active substance, improvement of organoleptic properties, changes in taste sensations, reduction of pain, wound healing, etc.

In certain embodiments, the compositions of the present invention contain essential oils. Essential oils are volatile aromatic oils, which may be synthetic or obtained from plants by distillation, expression or extraction, and which usually have the smell or taste of the plant from which they are derived. The essential oils used can provide antiseptic activity. Some of these essential oils also act as fragrance agents. Essential oils used include, without limitation, citrus, thymol, menthol, methyl salicylate (oil of wintergreen), eucalyptol, carvacrol, camphor, anethole, carvone, eugenol, isoeugenol, limonene, ozimene, n-decyl alcohol, citronel, a-salpineol, methyl acetate , Citronellyl Acetate, Methyl Eugenol, Cineole, Linalool, Ethyllinalaol, Safrole, Vanillin, Spearmint Oil, Peppermint Oil, Lemon Oil, Orange Oil, Sage Oil, Rosemary Oil, Cinnamon Oil, Allspice Oil, Laurel Leaf Oil, Cedar Leaf Oil , geraniol, verbenone, anise oil, laurel fruit oil, benzaldehyde, bergamot oil, bitter almond, chlorthymol, cinnamaldehyde, citronella oil, clove oil, coal tar, eucalyptus oil, guaiacol, tropolone derivatives such as hinokitiol, lavender oil, mustard oil, phenol, phenyl salicylate, pine oil, pine needle oil, sassafras oil, lavender broadleaf oil, styrax, thyme oil, tolu balsam, turpentine oil, clove oil, and combinations thereof.

In certain preferred embodiments, the present invention contains one or more bioactive essential oils selected from the group consisting of menthol, thymol, eucalyptol, and methyl salicylate. In certain preferred embodiments, the invention contains menthol and at least one other essential oil selected from thymol, eucalyptol and methyl salicylate. In certain preferred embodiments, the invention comprises menthol and eucalyptol, menthol, eucalyptol and thymol, or menthol, eucalyptol, thymol and methyl salicylate. Thymol [(CH ₃ ) ₂ CHC ₆ H ₃ (CH ₃ )OH, also known as isopropyl-m-cresol], is slightly soluble in water, but soluble in alcohol, and its presence in the composition is one of the reasons for the inclusion of alcohol in traditional incoming high-alcohol mouthwashes for sale. Methyl salicylate [C ₆ H ₄ OHCOOCH ₃ , also known as wintergreen oil] in addition to its antimicrobial function also provides a pleasant smell. Eucalyptol (C ₁₀ H ₁₈ O, also known as cineole) is a terpene ether and provides a cooling spicy taste. If desired, in certain formulations, eucalyptol can be used instead of thymol in the same dosage. Menthol (CH ₃ C ₆ H ₉ (C ₃ H ₇ )OH), also known as hexahydrothymol, is also slightly soluble in alcohol and quite volatile. In addition to its antiseptic properties, menthol provides a cooling tingling sensation.

Other useful antimicrobial agents include halogenated diphenyl ethers, 2',4,4'-trichloro-2-hydroxy-diphenyl ether (triclosan), 2,2'-dihydroxy-5,5'-dibromo-diphenyl ether, halogenated salicylanilides, 4',5-dibromosalicylanilide, 3,4',5-trichlorosalicylanilide, 3,4',5-tribromosalicylanilide, 2,3,3',5-tetrachlorosalicylanilide, 3,3',5-tetrachlorosalicylanilide, 3,5-dibromo -3'-trifluoromethyl salicylanilide, 5-n-octanoyl-3'-trifluoromethyl salicylanilide, 3,5-dibromo-4'-trifluoromethyl salicylanilide, 3,5-dibromo-3'-trifluoromethyl salicylanilide (fluorofen), benzoic acid esters, methyl-p -hydroxybenzoic ester, ethyl-p-hydroxybenzoic ester, propyl-p-hydroxybenzoic ester, butyl-p-hydroxybenzoic ester, halogenated carbanilides, 3,4,4'-trichlorocarbanilide, 3-trifluoromethyl-4,4'- dichlorocarbanilide,

3,3',4-trichlorocarbanilide, phenolic compounds (including phenol and its homologues, mono- and polyalkyl and aromatic halogen-containing (for example, F, Cl, Br, I) phenols, resorcinol and catechol and their derivatives and bisphenol compounds) , 2-methylphenol, 3-methylphenol, 4-methylphenol, 4-ethylphenol, 2,4-dimethylphenol, 2,5-dimethylphenol, 3,4-dimethylphenol, 2,6-dimethylphenol, 4-n-propylphenol, 4-n -butylphenol, 4-n-amylphenol, 4-tert-amylphenol, 4-n-hexylphenol, 4-n-heptylphenol, 2-methoxy-4-(2-propenyl)phenol (eugenol), mono- and polyalkyl and -aralkyl halophenols , methyl-p-chlorophenol, ethyl-p-chlorophenol, n-propyl-p-chlorophenol, n-butyl-p-chlorophenol, n-amyl-p-chlorophenol, sec-amyl-p-chlorophenol, n-hexyl-p -chlorophenol, cyclohexyl-p-chlorophenol, n-heptyl-p-chlorophenol, n-octyl-p-chlorophenol, o-chlorophenol, methyl-o-chlorophenol, ethyl-o-chlorophenol, n-propyl-o-chlorophenol, n -butyl-o-chlorophenol, n-amyl-o-chlorophenol, tert-amyl-o-chlorophenol, n-hexyl-o-chlorophenol, n-heptyl-o-chlorophenol, p-chlorophenol, o-benzyl-p-chlorophenol , o-benzyl-m-methyl-p-chlorophenol, o-benzyl-m, m-dimethyl-o-p-chlorophenol, o-phenylethyl-p-chlorophenol, o-phenylethyl-m-methyl-p-chlorophenol, 3 -methyl-p-chlorophenol, 3,5-dimethyl-p-chlorophenol, 6-ethyl-3-methyl-p-chlorophenol, 6-n-propyl-3-methyl-p-chlorophenol, 6-iso-propyl-3 -methyl-p-chlorophenol, 2-ethyl-3,5-dimethyl-p-chlorophenol, 6-sec-butyl-3-methyl-p-chlorophenol, 2-iso-propyl-3,5-dimethyl-p-chlorophenol , 6-diethylmethyl-3-methyl-p-chlorophenol, 6-iso-propyl-2-ethyl-3-methyl-p-chlorophenol, 2-sec-amyl-3,5-dimethyl-p-chlorophenol, 2-diethylmethyl -3,5-dimethyl-p-chlorophenol, 6-sec-octyl-3-methyl-p-chlorophenol, p-bromophenol, methyl-p-bromophenol, ethyl-p-bromophenol, n-propyl-p-bromophenol, n -butyl-p-bromophenol, n-amyl-p-bromophenol, sec-amyl-p-bromophenol, n-hexyl-p-bromophenol, cyclohexyl-p-bromophenol, o-bromophenol, tert-amyl-o-bromophenol, n -hexyl-o-bromophenol, n-propyl-m, m-dimethyl-o-bromophenol, 2-phenylphenol, 4-chlorine, 2-methylphenol, 4-chloro-3-methylphenol, 4-chloro-3,5-dimethylphenol , 2,4-dichloro-3,5-dimethylphenol, 3,4,5,6-tetrabromo-2-methylphenol, 5-methyl-2-pentylphenol, 4-isopropyl-3-methylphenol, 5-chloro-2-hydroxydiphenylmethane , resoncinol and its derivatives, resorcinol, methylresorcinol, ethylresorcinol, n-propylresorcinol, n-butylresorcinol, n-amylresorcinol, n-hexylresorcinol, n-heptylresorcinol, n-octylresorcinol, n-nonylresorcinol, phenylresorcinol, benzylresorcinol, phenylethylresorcinol, phenylpropylresorcinol, phenyl-resorcinol chlorobenzylresorcinol, 5-chloro-2,4-dihydroxyphenylmethane, 4'-chloro-2,4-dihydroxyphenylmethane, 5-bromo-2,4-dihydroxyphenylmethane, 4'-bromo-2,4-dihydroxyphenylmethane, bisphenolic compounds, bisphenol A, 2,2'-methylene-bis(4-chlorophenol), 2,2'-methylene-bis(3,4,6-trichlorophenol)(hexachlorophene), 2,2'-methylene-bis(4-chloro-6- bromphenol), bis(2-hydroxy-3,5-dichlorophenyl)sulfide, bis(2-hydroxy-5-chlorobenzyl)sulfide, methoxy-1,2-propanediol, ortho-methoxycinnamic aldehyde, methyl-3-hydroxybutanoate, combinations of two or more of them, etc.

Other antimicrobial agents include, without limitation: hexetidine; fatty acid compounds such as caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, myristolenic acid, palmitic acid, palmitolenic acid, stearic acid, oleic acid, elaidic acid, linoleic acid, linolenic acid, linoleic acid, arachidonic acid , vitamin E, vitamin E acetate, apigenin and mixtures thereof; long-chain fatty alcohols such as those described in U.S. Patent Publication No. 20110123462 Mordas et al., incorporated herein in its entirety by reference (examples of which include, without limitation, 1-decen-3-ol; cis-4-decen-1 -ol, trans-2-decen-1-ol, cis-2-nonen-1-ol, cis-4-decenal, trans-2-decenal, cis-7-decenal, cis-5-octen-1-ol , trans-2-octen-1-ol, 1-octen-3-ol, cis-3-nonen-1-ol, trans-2-nonen-1-ol, cis-6-nonen-1-ol, 9 -decen-1-ol, trans-2-undecen-1-ol, trans-2-dodecen-1-ol, trans-2-octenal, trans-2-nonenal, 6-nonenal, cis-2-decenal, trans -2-undecenal, trans-2-dodecenal, cis-3-octen-1-ol, 3-octen-2-ol, 10-undecen-1-ol, trans-2-tridecen-1-ol, their stereoisomers and their mixtures); cyclic sesquiterpene alcohols such as farnesol; N′-alkyl L-arginine alkyl ester (eg, lauroyl arginine ethyl ester) and salts such as those described in US Patent No. 5,874,068 to Engelman et al. amino acid derivative compositions as described in US Patent Publication No. 20160145203, Gambogi, et al., herein incorporated herein in its entirety by reference; antimicrobial peptides such as retrocyclin (RC101), protegrin-1 (PG1) or KSL-W; and surfactants, including cationic surfactants such as cetylpyridinium chloride, chlorhexidine, and mixtures thereof. In addition, antimicrobial extracts of certain plants or fruits may be included, including the proanthocyanidins (PACs) found in cranberries, such as flavan-3-ols (and their polymers), procyanidins (and their polymers), terpenes (and their polymers). ), hydroxybenzoic acids, hydroxycinnamic acids, anthocyanidins (and their polymers), flavonols (and their polymers), and other cyanidins and peonidins. In addition, oils such as peppermint oil and sage oil are used.

Other suitable actives include fluoride ion sources such as sodium fluoride, sodium monofluorophosphate, tin fluoride, and amine fluorides (providing, for example, about 1-5000 ppm fluoride ions, optionally about 200-1150 ppm fluoride ions ); non-fluoride tooth strengthening agents such as calcium carbonate, alphatricalcium phosphate or calcium phosphoryl oligosaccharides, antitartar agents such as water soluble pyrophosphate salts, preferably alkali metal pyrophosphates, polyacrylates and copolymers of maleic anhydride or acid and methyl vinyl ether (e.g. Gantrez ) as described, for example, in US patent No. 4,627,977, Gaffar et al.; as well as, for example, polyaminopropanesulfonic acid (AMPS), zinc citrate trihydrate, polypeptides (such as polyaspartic and polyglutamic acids) and mixtures of two or more of them; antitartar agents such as water-soluble pyrophosphate salts, preferably alkali metal pyrophosphates; chelating agents such as tartaric acid and its pharmaceutically acceptable salts, citric acid and alkali metal citrates and mixtures thereof; dental desensitizing agents that desensitize teeth, including potassium salts such as potassium nitrate and potassium chloride, and strontium salts such as strontium chloride and strontium acetate; teeth whitening agents and vitamins such as vitamin A; as well as pigments and dyes such as inorganic white pigments, inorganic color pigments, pearlescent agents, powder fillers, etc., as well as talc, mica, magnesium carbonate, calcium carbonate, magnesium silicate, aluminum-magnesium silicate, silicon dioxide, Titanium Dioxide, Zinc Oxide, Iron Oxide Red, Iron Oxide Brown, Iron Oxide Yellow, Iron Oxide Black, Ferric Ammonium Ferrocyanide, Deep Purple Dye, Ultramarine, Nylon Powder, Polyethylene Powder, Methacrylate Powder, Polystyrene Powder, Silk Powder, Crystalline cellulose, starch, titanium-containing mica, titanium-containing iron oxide, bismuth oxychloride, and mixtures of two or more of them.

Enzymes are another type of active substance that can be used in the present compositions. Enzymes used include those categorized as proteases, lytic enzymes, plaque matrix inhibitors and oxidases: proteases include papain, pepsin, trypsin, ficin, bromelain; lytic cell wall enzymes include lysozyme; plaque matrix inhibitors include dextranases, mutanases; and oxidases include glucose oxidase, lactate oxidase, galactose oxidase, uric acid oxidase, peroxidases including horseradish peroxidase, myeloperoxidase, lactoperoxidase, chlorine peroxidase. Oxidases also have whitening/cleansing activity in addition to antimicrobial properties.

Ingredients metabolized by oral bacteria with beneficial effects on the oral cavity may also be included in these materials, including arginine, arginine monohydrochloride and inulin-like fructans, maltodextrin, fructooligosaccharides and galactooligosaccharides. In addition, the invention can be used to deliver probiotic strains of bacteria, including certain species of lactobacilli and bifidobacteria, species of Saccharomyces, streptococci, enterococci and commensal Escherichia coli.

The invention can also be applied to the delivery of pharmaceutically active substances for the treatment of diseases of the oral cavity or symptoms of diseases that occur in the oral cavity or oropharynx, such as anesthetics, antibiotics, antifungal, antiviral and anti-inflammatory compositions.

METHODS OF OBTAINING

Any suitable means may be used to prepare the coated particles of the present invention. In certain embodiments, the methods include reacting the coating materials/polymers with the substrate materials under conditions sufficient to covalently bond the materials/polymers to the surface of the substrate materials. In other embodiments, the implementation of the methods include the adsorption of the coating material on the substrate. The following are examples of general methods for producing coated PLGA particles as non-limiting examples of the present invention. In such a method, other substrate particles of the present invention can also be used in place of PLGA.

Surface bonding

PLGA particles contain carboxyl groups on the surface, which can be used to interact with the amino groups of biological compounds to form covalent bonds. The binding protocol below serves as general guidelines for obtaining PLGA particles bound to biomolecules (coating materials).

1. Prepare a suspension of PLGA particles by shaking in 50 mM MES buffer (pH 5.2) (company, product code). If necessary, sonicate.

2. Prepare a solution of 200 mg/mL EDC N- (3-dimethylaminopropyl) -N' -ethylcarbodiimide hydrochloride (Sigma Aldrich cat. no. E1769) in 50 µl of 50 mM MES buffer (pH 5.2); Apply immediately.

3. Add the EDC solution to the microsphere suspension.

4. Gently mix by inverting.

5. Add the biomolecule in an amount equivalent to 200–500 µg. Mix gently by inverting or shaking once.

6. Incubate for 2-4 hours at room temperature with gentle agitation.

7. Centrifuge the mixture for 10 minutes at an appropriate g. Note. The actually used values of g required for the formation of a dense deposit depend on the particle size. Save the resulting supernatant for quantification of the bound biomolecule.

8. Resuspend the resulting microsphere pellet in 10 mM Tris buffer containing 0.05% BSA (pH 8.0).

9. Repeat steps 7-8 and pool supernatants for use in calculating the amount of bound biomolecule.

10. Store microsphere conjugate at 4 °C in Tris storage buffer.

EDC was used for peptide synthesis; cross-linking of proteins with nucleic acids; and obtaining immunoconjugates as examples. EDC is essentially used as an activating agent for carboxyl groups in the coupling of amides to primary amines. In addition, it will react with phosphate groups.

Adsorption

1. Prepare a suspension of 50 mg of PLGA particles in 1 ml of water to obtain a mixture of PLGA particles at a concentration of 5 wt.%.

2. Add PLGA particles mixture equivalent to 2.5 mg of PLGA particles (i.e. 50 µl) to 500 µl of process solution, mix gently by inverting for 30 minutes at room temperature.

3. Centrifuge at 1500 g for 20 minutes.

APPLICATIONS

Applicants have found that the coated particles of the present invention can be used to administer active agents or to prevent, treat, or provide benefits to oral surfaces. In particular, the particles may be administered to the oral cavity to attach to one or more of its surfaces to deliver active agents and/or provide a beneficial effect on the oral cavity.

The particles of the present invention may contain any of a variety of active materials to provide a beneficial effect on the oral cavity. In accordance with certain embodiments, the methods of the present invention include administering the coated particle of the present invention to the oral cavity to provide one or more beneficial effects selected from the group consisting of: disrupting biofilm on the oral surface, weakening bacterial adhesion on the oral surface, removing biofilms from the surface, inhibiting the action of plaque and the formation of plaque, reducing inflammation of the gums, swelling and redness of the gums, reducing bleeding and preventing gingivitis.

In accordance with the methods of the present invention, any acceptable surface of the oral cavity may come into contact, including one or more surfaces selected from the group consisting of surfaces of one or more teeth, surfaces of the gums, combinations of two or more of them, and the like. In certain in preferred embodiments, the coated particles are used to contact the tooth surface.

In each of the above methods, the composition according to the claimed method can be applied to the surface to be contacted by any of a variety of methods. In certain embodiments, the user introduces the composition into the oral cavity and applies it to the surface as a mouthwash or rinse. In certain embodiments, the composition is administered to the oral cavity and applied to the surface as a toothpaste on a dentifrice product, such as a toothbrush. The compositions of the present invention may additionally be administered orally and applied to the surface as a chewing gum, lozenge, dissolvable wafer, or the like.

In addition, the step of contacting the methods of the present invention may include contacting the surface with the composition for any suitable amount of time. In certain embodiments, the contact step includes contacting the surface for less than thirty seconds. In certain embodiments, the contact step includes contacting the surface with the composition for thirty seconds or more, such as for about thirty seconds, for about forty seconds, for about one minute, or for more than one minute.

ANALYSIS

Applicants have developed new assay techniques to determine the ability of coated materials to adhere to oral surfaces, in particular hydroxyapatite surfaces (tooth surfaces). In certain embodiments, the assay comprises coating hydroxyapatite (HAP) particles with saliva, mixing the saliva-coated HAPs with the polymer-coated PLGA particles to be tested, and incubating, washing the resulting HAPs with the coated PLGA particles of interest to remove free PLGA particles from polymer under test and collecting the eluent, and measuring the collected eluent to determine the fluorescence intensity. Based on these methods, the fluorescence of the eluent can be used to determine the amount of coated particles adhered to HAP and washed off. In particular, particle binding assay techniques provide an assessment of the interaction that occurs between polymer-coated PLGA particles and saliva-coated HAP, such as polymer-film binding, as well as the degree of affinity (weak, strong, or no interaction) with which the reactants bind to each other. .

The following is an example of a procedure in accordance with one embodiment using PLGA particles.

Procedure for Fluorescent Assay of PLGA Particle Binding

1. Weigh out x mg HAP particles (enough for 10 mg per sample well, eg 10 sample wells 100 mg HAP).

2. Add artificial saliva at a concentration of 100 µl per 10 mg to the particles and incubate for 15 minutes at 37 °C.

3. Transfer the HAP particle/saliva suspension to a 3.0 µm filter plate by adding 100 µl to the suspension in each appropriate well. Use a single channel pipette and agitate the suspension before pipetting the sample.

4. Separate the saliva from the wells of the filter plate by vacuum filtration. Tape should be used to cover the wells because the vacuum is not deep enough to remove all the liquid without tape. NOTE. It may take several cycles to cover the plate with tape, remove it, and recoat it.

5. Add polymer-coated particles to each well and incubate at 37°C for 10 minutes with shaking (avoid too long incubation).

6. Remove treatment fluid by repeating step 4. NOTE. Collect eluent.

7. Wash off any loosely bound polymer-coated fluorescent PLGA particles from the HAP particles using 200 µl of water. NOTE. Collect eluent.

8. Repeat step 7 until the fluorescence disappears. NOTE. Collect the eluent after each repetition. Follow the product and record the color (after all three washes, the final eluent should be a clear solution).

9. Add all eluents from steps 6-8 to a 96-well opaque or black bottom plate.

10. Measure fluorescence on an opaque or black 96-well plate. Excitation/Emission: 460/500 nm.

Below is another embodiment.

Fluorescence analysis of the adsorption of PLGA particles

Procedure

1. Weigh out x mg of HAP particles (x=sufficient for 10 mg per sample well, for example 100 mg of HAP would be weighed out for 10 sample wells).

2. Add artificial saliva at a concentration of 100 µl per 10 mg to the particles and incubate for 30 minutes to 24 hours at 37 °C with constant shaking.

3. After incubation, transfer the HAP particle/saliva suspension to a 3.0 µm filter plate by adding 100 µl to the suspension in each appropriate well. Use a single channel pipette and agitate the suspension before pipetting the sample.

4. Separate the saliva from the wells of the filter plate by vacuum filtration. Aluminum foil should be used to cover the wells because the vacuum is not deep enough to remove all liquid without aluminum foil. NOTE. Several cycles of foil coating, removal, and recoating of the plate may be required.

5. Adsorption

i. Prepare a suspension of 50 mg of PLGA particles in 1 ml of water to obtain a mixture of PLGA particles at a concentration of 5 wt.%.

ii. Add PLGA particles mixture equivalent to 2.5 mg PLGA particles (i.e. 50 µl) to 500 µl of process solution, gently mix by inverting for 30 minutes at room temperature.

iii. Centrifuge at 1500 g for 20 minutes.

6. Carefully remove the supernatant with a pipette without stirring up the precipitate formed.

7. After separating the precipitate, add XX µl of deionized water to the tube. Re-suspend the precipitate in water by shaking with stirring. (XX=120 µl multiplied by the number of wells in each method). The resulting solution will be used to measure the total fluorescence in this method.

8. Add polymer-coated particles to each well and incubate at 37°C for 10 minutes with shaking (avoid too long incubation).

9. Remove treatment fluid by repeating step 4. NOTE. Collect eluent.

10. Wash off any loosely bound polymer-coated fluorescent PLGA particles from the HAP particles using 100 µl of deionized water. NOTE. Collect eluent.

11. Repeat step 10 until the fluorescence disappears. NOTE. Collect the eluent after each repetition. Follow the product and record the color (after all three washes, the final eluent should be a clear solution).

12. Add 75 µl of each eluent and total fluorescence solution after steps 7-11 to a 96-well opaque or black bottom plate.

13. Measure the fluorescence intensity with the Tecan infinite M200 in an opaque 96 well plate or in a plate with a black clear bottom. Excitation/Emission: 460/500 nm, Gain: 50.

Note.

For 13871-10, the incubation of HAP particles in artificial saliva (step 2) was 24 hours.

For 13871-12, the incubation of HAP particles in artificial saliva (step 2) was 2 hours.

EXAMPLES

Example 1

Applicants prepared several coated particles in accordance with the surface binding procedure of the present invention described herein. As shown in Tables 1-2, Applicants coated PLGA particles from leucine, valine, tryptophan, methionine and arginine with chitosan and xanthan gum, with polyvinylpyrrolidone (Plasdone K29/32), ethyl lauryl alginate hydrochloride (LAE) and with several compounds of formula I These coated particles were subsequently analyzed according to the PLGA-particle fluorescence binding assay procedure described herein and the results are summarized in Tables 1 and 2 below.

Table 1

Control LAE HLA HMP PSSA eluate 1 44004 53131 51145 46139 45424 eluate 2 44258 55917 55056 47294 46104 flush 1 44989 54437 48126 46326 46941 flush 2 19323 19844 29424 16783 22667 flush 3 6163 9800 12342 6276 7785 flush 4 4102 6124 8299 3732 3111

table 2

Counter. H20 HLA 17 18 31 Leucine Valine Trip-tofan Methionin Arginine K29 Chitosan Iron xanthan gum 1 3 4 5 6 7 8 9 10 eleven 12 13 14 15 eluate 1 40179 40940 46331 45981 47077 44022 43637 42969 43874 43544 42235 41487 37783 38275 eluate 2 41602 39325 44069 not eluate not eluate 43775 39421 41819 42047 43597 42833 41400 not eluate 40309 flush 1 33717 40128 40072 not eluate not eluate 36404 37812 38450 38765 42145 38568 42579 not eluate 42501 flush 2 10541 20092 16709 not eluate not eluate 15709 19342 17180 15714 17362 15563 32460 not eluate 35681 flush 3 3023 8046 5902 50511 51951 5150 4276 4255 3525 4069 4930 26204 42823 6160 flush 4 1490 4353 3129 33023 36129 2540 2594 2047 1858 2129 2494 19569 26957 24156 flush 5 1329 2945 1734 19396 17702 1612 1795 1338 1292 1448 1519 12608 9313 33728

The results in the tables reflect the degree of binding for each polymer-coated PLGA particle to saliva-coated HAP. Among the polymers providing particularly strong bonding were chitosan and xanthan gum. Strong binding was observed for LAE, HLA and compounds 17, 18 and 31 . Moderate binding was recorded for all amino acids and PVP. PSSA showed weak binding, and the molecules that showed no interaction were iron and HMP.

Example 2

Applicants prepared and tested several coated particles in accordance with the fluorescent adsorption assay of the PLGA particles of the present invention, which is described herein, using the materials listed in the tables. As shown in the tables, Applicants coated the particles with distearmonium/diethonium chloride PG dimethicone (Silquat J2 4B), chitosan (Chitosan LMW), polyquaternium-10 (Ucare JR 30 M, Ucare LR-400), myristamidopropyl PG-dimonium chloride phosphate (Arlaskil PTM-LQ-AP), dimethicone phosphate PEG-8 (Siliphos A-100) and methyl methacrylate (MMA) and diaethylaminoethyl methacrylate (DEAEMA) (Kollicoat Smart Seal 30D).

Calculation

For the calculation, we used the initial data obtained using a device for recording fluorescence. The average of the total fluorescence results for each technology was calculated to obtain the average intensity of the total fluorescence. Data for collected eluents and washes were normalized to the average total fluorescence of the respective resuspended PLGA particles and procedures. This value was calculated for each well of the sample for all washes treated on the basis of various methods. The following formula was used for normalization:

(Initial value of fluorescence of the eluent in the washout of the sample well of a particular technique / average intensity of the total fluorescence for such a technique) * 100

For each stage of flushing of the corresponding technique, the mean and standard deviation were calculated. The constructed graph shows the values of the normalized fluorescence intensity for each technology, and the error bars reflect the standard deviation of the normalized data.

Table 3

Total fluorescence 1% Silquat JR-4B Water 0.25% Chitosan LMW 0.25% Ucare JR 30M 0.25% Ucare LR 400 Arlasilk PTM–LQ–AP Siliphos A 100 Kollicoat Smart Seal 30D 1 4603 4255 4664 2405 3535 4647 4357 7020 2 4936 4746 5116 4789 3281 4877 4547 7662 Avg. meaning 4769.5 4500.5 4890 3597 3408 4762 4452 7341

Table 4

Initial data 1% Silquat JR-4B Water 0.25% Chitosin LMW 0.25% Ucare JR 30M 0.25% Ucare LR 400 Arlasilk PTM–LQ–AP Siliphos A 100 Kollicoat Smart Seal 30D Eluate for processing 1251 2523 2855 8 90 943 3231 29 1277 2498 2876 8 87 1002 3293 35 1303 2676 2928 5 38 1049 2974 thirty Flush 1 363 1513 1724 4 217 654 1893 5 364 1551 1888 4 203 496 1819 5 361 1562 2055 3 93 531 1856 6 Flush 2 61 181 176 4 118 170 216 3 49 154 210 1 127 55 130 3 47 143 156 2 68 195 101 2 Flush 3 43 114 128 2 93 88 32 1 thirty 145 83 3 81 32 29 2 32 147 83 3 29 67 27 1

Table 5

Total fluorescence

1% PQ6 0.5% PQ6 0.25% PQ6 0.25% Ucare LR400 0.125% Ucare LR400 Water 0.25% Ucare JR 400 0.125% Ucare JR 400 1% Kollicoat smartseal 30 D 0.5% Kollicoat smartseal 30D 0.25% Kollicoat smartseal 30D 1 3258 3617 3837 3967 2966 3805 2091 3850 6352 8996 7048 2 3653 3545 3867 4072 3047 3885 2217 3829 6502 8339 7140 Avg. 3455.5 3581 3852 4019.5 3006.5 3845 2154 3839.5 6427 8667.5 7094

Table 6

Initial data

1% PQ6 0.5% PQ6 0.25% PQ6 0.25% Ucare LR400 0.125% Ucare LR400 Water 0.25% Ucare JR 400 0.125% Ucare JR 400 1% Kollicoat smartseal 30D 0.5% Kollicoat smartseal 30D 0.25% Kollicoat smartseal 30D Waste 1688 1411 1308 866 200 2680 260 1315 4 4 23 1699 1266 1123 748 272 2515 420 1357 3 3 19 1748 1128 1183 757 345 2663 372 1334 3 6 19 Flush 1 844 652 768 1111 58 1495 101 1543 2 2 10 901 889 910 1211 62 1403 153 1718 2 1 21 918 808 953 1063 81 1521 130 1536 3 2 21 Flush 2 163 199 287 430 3 102 2 263 1 2 9 155 214 346 481 4 147 2 323 2 1 6 135 245 354 509 3 126 2 416 1 1 10 Flush 3 56 83 129 284 3 38 2 174 1 1 5 56 111 199 329 3 41 1 180 2 2 4 67 121 172 344 4 43 1 211 2 1 9

The results in the tables reflect the degree of affinity for each method of polymer coating of PLGA particles for saliva-coated HAP. Polymers that exhibited very strong to strong binding (0-10% and 10-25% fluorescence in wash eluates) included polyquaternium-10 (e.g., UCare LR 400, UCare JR 30, UCare JR 400), a copolymer comprising methyl methacrylate (MMA) and diethylaminoethyl methacrylate (DEAEMA) (eg Kollicoat Smart seal 30 D). Polymers for which moderate binding (25-40% fluorescence in wash eluates) have been observed include polyquaternium-6 (e.g. Tilamar Quat 640), PG-dimonium myristamidopropyl chloride phosphate (e.g. Arlasilk PTM), silicones (e.g. distearmonium chloride/ dietonium PG dimethicone, Silquat J2 4B). Molecules that showed little to no binding (40% < fluorescence in wash eluates) include water, low molecular weight chitosan, anionic molecules (eg Siliphos A 100).

Retention calculation. The retention percentage was calculated with an assumed total percentage equal to 100%. Percentages for normalized post-treatment eluates and washes were subsequently subtracted from 100% total fluorescence to measure the degree of affinity (percent retention) for each polymer coating technique of PLGA particles for saliva-coated HAPs.

The results in the tables reflect the degree of affinity for each method of polymer coating of PLGA particles for saliva-coated HAP. Polymers that showed very strong to strong retention (90-100% and 75-90%) included polyquaternium-10 (e.g., UCare LR 400, UCare JR 30, UCare JR 400), a copolymer comprising methyl methacrylate (MMA) and diethylaminoethyl methacrylate (DEAEMA) (eg Kollicoat Smart seal 30 D). Polymers of which moderate binding (60-75%) has been observed include polyquaternium-6 (eg Tilamar Quat 640), PG-dimonium myristamidopropyl chloride phosphate (eg Arlasilk PTM), silicones (eg distearmonium/diethonium chloride PG dimethicone, Silquat J2 4B). Molecules that exhibited from weak binding to no binding (40–60% and 40%>) include water, low molecular weight chitosan, anionic molecules (eg Siliphos A 100). This interaction is also visualized in the photographs of the respective wells using yellow-green saturation.

Claims (6)

1. A coated particle that binds to, attaches to or connects to the surface of the oral cavity, containing: (a) a substrate, which is a particulate or nanoparticle derived from a copolymer of lactic and glycolic acids (PLGA), and (b) a coating covalently bonded to the substrate, which is ethyl lauryl arginate hydrochloride. 2. Particle according to claim 1, additionally containing an active ingredient. 3. A method for providing a beneficial effect on the oral cavity, including the introduction of a coated particle according to claim 1 into the specified oral cavity. 4. A method for providing a beneficial effect on the oral cavity, including introducing into the specified oral cavity the coated particle according to claim 2.