CN105412143A

CN105412143A - Oral cavity composition containing polyguanidine compounds and preparation and application method of oral cavity composition

Info

Publication number: CN105412143A
Application number: CN201510570435.4A
Authority: CN
Inventors: A.诺瓦克; S.皮尔奇; J.马斯特斯
Original assignee: Colgate Palmolive Co
Current assignee: Colgate Palmolive Co
Priority date: 2009-05-18
Filing date: 2009-05-18
Publication date: 2016-03-23

Abstract

The invention relates to an oral cavity composition containing polyguanidine compounds and a preparation and application method of oral cavity composition. Modification of a material based on polyamine is described so as to form the polyguanidine compounds of which the antimicrobial, tooth decay prevention and mucus adhesive properties can be utilized. The invention further relates to a method for preventing or treating a periodontal disease and decayed teeth. The method comprises the step of delivering treatment effective dose of the oral cavity composition containing the polyguanidine compounds to an oral cavity.

Description

Oral cavity composition containing poly-guanidine compound and preparation and application thereof

The application is the applying date is on May 18th, 2009, and application number is 200980159445.1 (international application no is PCT/US2009/044349), and denomination of invention is " containing poly-guanidine the oral cavity composition of compound and preparation and application thereof " the divisional application of application for a patent for invention.

Invention field

The present invention includes the oral care composition being included in the polyguanidine compound distributed in the acceptable carrier of oral cavity.The present invention also comprises method for the preparation of the oral cavity composition containing polyguanidine compound and using method thereof.The present invention also comprises makes active component targeting oral epithelium tissue, deposit antibacterial material or sterilization material on an oral surface, postpone or prophylaxis of teeth dental caries, treatment or prevention odontohyperesthesia, blocking dential canaliculi, treatment carious lesions, makes the pulp calcification of exposure, and making the method for the pit of tooth or the substrate in crack or whole calcifications etc., described method comprises the oral cavity composition comprising polyguanidine compound of delivery treatments effective dose in oral cavity.

Background of invention

Periodontal disease and dental caries are most popular dental problems.Except affecting oral cavity tissue, periodontal disease is also relevant to multiple general disease.The feature of gingivitis (mild forms of disease) is host tissue inflammation and the accumulation of the antibacterial dental plaque around gingival edge.Treating gingivitis by the oral hygiene practice improved can remarkable reverse disease situation.But leave not treat, gingivitis can cause more serious and irreversible periodontitis, periodontitis to comprise progressively losing periodontal alveolar bone, and leaves not treat, and tooth can be caused loose and lose subsequently.

Dental caries is the communicable odontopathy of most, and can cause enamel, dentine and cementum demineralization and loss.If do not treated, cause the antibacterial dental plaque of dental caries also can cause dentin hypersensitiveness and pain, and lose tooth subsequently.As the end product of the bacterial degradation of fermentable carbohydrate, acid dissolve hydroxyapatite, this hydroxyapatite is the calcium phosphate mineral forming enamel, dentine and cemental most of mineral.Acidizer (comprising some food and oral cavity personal care product) also can cause tooth demineralisation.In the latter, many is commercially available collutory and grinding toothpaste.

Summary of the invention

The present invention includes the compositions of the material comprised based on polyamine, the described material based on polyamine forms the polyguanidine compound that can utilize their antimicrobial, preventing decayed tooth and mucus bond property.Therefore, the present invention includes polyguanidine compound, described polyguanidine compound comprises the active component had with character in antimicrobial and acid, with the antibacterial dental plaque that targeting is relevant with dental caries with the periodontal disease in such as oral cavity.

In one embodiment, the present invention includes a kind of oral cavity composition, described oral cavity composition contains the polyguanidine compound and oral cavity acceptable carrier that comprise gegenion.

In another embodiment, the present invention includes the method for the preparation of oral cavity composition, described oral cavity composition is included in the polyguanidine compound comprising gegenion distributed in the acceptable carrier of oral cavity.

In another embodiment, present invention resides in the method for anti-bacteria dental plaque in oral cavity, described method comprises to be made mammiferous oral epithelium tissue and/or tooth and comprises the compositions comprising the polyguanidine compound of gegenion for the treatment of effective dose and contact.

In another embodiment, the present invention includes the method for the prevention periodontal disease in oral cavity and dental caries morbidity, described method comprises to be made mammiferous oral epithelium tissue and/or tooth and comprises the compositions comprising the polyguanidine compound of gegenion for the treatment of effective dose and contact.

In another embodiment, present invention resides in the method for antibacterial material or the sterilization material retained after oral surfaces is deposited on brush or rinsing, described method comprises the oral cavity composition comprising the polyguanidine compound of gegenion sent in oral cavity and comprise treatment effective dose.

In another embodiment, the present invention includes delay or the method for prophylaxis of teeth dental caries, described method comprise in oral cavity delivery treatments effective dose containing the oral cavity composition of polyguanidine compound comprising gegenion.

In another embodiment, the present invention includes the method for the treatment of or prevention odontohyperesthesia, described method comprise in oral cavity delivery treatments effective dose containing the oral cavity composition of polyguanidine compound comprising gegenion.

In another embodiment, the present invention includes the method for inaccessible dential canaliculi, described method comprise in oral cavity delivery treatments effective dose containing the oral cavity composition of polyguanidine compound comprising gegenion.

In another embodiment, the present invention includes the method for the treatment of carious lesions, described method comprise in oral cavity delivery treatments effective dose containing the oral cavity composition of polyguanidine compound comprising gegenion.

In another embodiment, the present invention includes the method for the pulp calcification making exposure, described method comprise in oral cavity delivery treatments effective dose containing the oral cavity composition of polyguanidine compound comprising gegenion.

In another embodiment, the present invention includes the method making the pit of tooth or the substrate in crack or all calcifications, described method comprise in oral cavity delivery treatments effective dose containing the oral cavity composition of polyguanidine compound comprising gegenion.

Accompanying drawing is sketched

Fig. 1 illustrates a series of images using the inaccessible dential canaliculi of compositions disclosed herein.

Fig. 2 is the acid proof a series of images that dentin surface after by compositions-treated disclosed herein is described.

The figure of the comparison between the dentine electrical conductivity that Fig. 3 measures for explanation reference composition and compositions-treated disclosed herein.Line representative is above containing the sample of bioactivity glass, and line representative below contrasts.

Detailed Description Of The Invention

The present invention includes oral care composition comprising polyguanidine compound or its salt and oral cavity acceptable carrier and preparation method thereof.The present invention also comprises the method for preventing or treat periodontal disease and dental caries, and described method comprises the oral cavity composition sending the polyguanidine compound or its salt comprising treatment effective dose in oral cavity.

i. polyguanidine compositions

The present invention includes oral care composition, described oral care composition comprises the polyguanidine compound or its salt that at least one can utilize its antimicrobial, preventing decayed tooth and/or mucus bond property.Comprise polyguanidine compound in the present invention and salt can deposit therapeutic agent and gegenion on an oral surface, suppress the growth of long-time antibacterial class biology after using described compositions as antimicrobial, and keep the pH that raises and promote remineralization.In some embodiments, polyguanidine compositions of the present invention comprises: at least one polycation material, at least one gegenion class material and at least one oral cavity acceptable carrier.

A. poly-(guanidine of the present invention ) compound

The present invention includes and comprise at least one and gather guanidine the oral cavity composition of compound.Term used herein " polyguanidine " or " poly-guanidine " be used interchangeably and refer to the compound of formula (I):

Wherein

When Z is CH, R ₁for hydrogen, hydroxide, methoxyl group compound and straight or branched, saturated or undersaturated optional hydroxylated C _1-c ₁₆alkyl, or when Z is N, R ₁for hydrogen and straight or branched, saturated or undersaturated optional hydroxylated C ₁-C ₁₆alkyl;

R ₂and R ₃be hydrogen or straight or branched, saturated or undersaturated optional hydroxylated C independently of one another ₁-C ₁₆alkyl;

A is covalent bond or straight or branched, saturated or undersaturated optional hydroxylated C ₁-C ₁₆alkyl;

Z is CH or N;

X ^-for gegenion, such as, bicarbonate radical or chloride ion; With

N is between 2-5, the integer of 000.

Poly-guanidine of the present invention the ion that compound can exist the acceptable band multi-charge in oral cavity maybe can dissociate the salt of the ion becoming band multi-charge, and it has clean positive charge.In some embodiments, described polycation material is polyamine.In some embodiments, described polycation material is poly-guanidine compound.

In some embodiments, described polyguanidine compound comprises at least one side base (R ₁).In some embodiments, described side base (R ₁) be hydrogen; Hydroxyl; With straight or branched, saturated or undersaturated optional hydroxylated C ₁-C ₁₆alkyl.In one embodiment, described side base is hydrogen atom.

In some embodiments, described polyguanidine compound comprises carbohydrate chain (A).In some embodiments, described alkyl chain (A) be straight or branched, saturated or undersaturated optional hydroxylated C ₁-C ₁₆alkyl.In some embodiments, described alkyl chain (A) is comprised by least one straight or branched, the saturated or undersaturated C that following group optionally replaces ₁-C ₁₆alkylidene: hydroxyl, carboxyl, carboxylate group or halogen; The optional alkylidene being selected from following functional group containing at least one: amine, ether, thioether, ester, amide, carbamate, urea, by C ₁-C ₈the C that alkyl, hydroxyl or halogen optionally replace ₆aryl or C ₃-C ₈ring.In some embodiments, described alkyl chain (A) is for one or more unsubstituted or by C ₁-C ₈the C of alkyl, hydroxyl or halogen substiuted ₆or C ₇aryl or C ₅-C ₇cycloalkyl ring.In some embodiments, described carbohydrate chain (A) is selected from: C ₁₀-C ₁₄polyaryl or C ₆-C ₁₀multi-ring alkyl chain, it can be selected from following functional group interval by least one: C ₁-C ₈alkylidene, amine, amide, ether, thioether, hydrogen atom, carbamate or urea.

In some embodiments, described polyguanidine compound comprises n unit, and wherein n represents between 2-5, the integer of 000.

In certain embodiments, described poly-guanidine compound is:

In some embodiments, described polyguanidine compound has anti-microbial properties.In one embodiment, the antimicrobial acivity of polyguanidine compound is owing to there is strong basicity cationic structural, being similar to hibitane.Be not wishing to be bound by theory, the mechanism of this effect is due to positive charge, and this positive charge is attracted by force by the acidic-group occurred in sialoprotein.As a result, the pellicle of this positive charge in oral cavity and soft tissue are combined by force, this positive charge can stop exceedance hour wherein.Therefore, Ca needed for pellicle and gingiva is adhered to by adhering to electronegative bacteria wall and dividing antibacterial dental plaque subsequently ²⁺salt bridge, poly-guanidine salt anti-bacteria grows in the oral cavity.In one embodiment, polyguanidine compound of the present invention is polycation, because they have common antimicrobial acivity to the affinity of electronegative bacteria cell wall.In one embodiment, the interaction of this opposite charges causes relevant with bacterial membrane and divides bacterial membrane, and anti-bacteria dental plaque can be caused to adhere to or bacterial cell death.

In some embodiments, poly-guanidine of the present invention compound has mucus bond property.In some embodiments, these mucus bond properties comprise electrostatic and lipotropy interaction.Due to membrane glycoprotein and glycolipid, oral surfaces (comprising mucous epithelium) has net negative charge.Glycoprotein in saliva is also containing overall negative charge.In addition, oral surfaces contains and a large amount of is embedded in phosphate in cell membrane and the electrically charged class material of bidentate, and they can interact with polycation, to produce the strong binding agent lipophilic moieties that can cross cytolipin plasma membrane.Therefore, in one embodiment, poly-guanidine of the present invention compound has strong affinity due to electrostatic interaction to oral mucosa surface.

In one embodiment, described poly-guanidine compound is formed and bonds lipophilic moieties by force, and this lipophilic moieties can be attracted in oral cavity tissue.In one embodiment, described polyguanidine compound is by the relevant direct targeting oral surfaces of active component.In one embodiment, the absorption of described polyguanidine compound promoted active component in oral cavity tissue.In one embodiment, described active component is selected from antibacterial material and sterilization material.In one embodiment, described polyguanidine compound deposits antibacterial material or sterilization material on an oral surface, and these materials retain long-time after brush and rinsing.

B. gegenion

In some embodiments, oral care composition of the present invention comprises at least one gegenion class material.In some embodiments, the source of gegenion is selected from: antimicrobial, anti-caries agent and acid-neutralization compound.In some embodiments, oral cavity composition of the present invention combines and is selected from following gegenion: carbonate and phosphate radical.In some embodiments, described gegenion class material is carbonate.In some embodiments, described gegenion class material is bicarbonate radical.In some embodiments, described gegenion class material is phosphate radical.In some embodiments, described gegenion class material is chloride ion.

In one embodiment, described at least one gegenion class material is bicarbonate radical.In some embodiments, oral cavity composition of the present invention also comprises the second gegenion class material.In some embodiments, described second gegenion class material is carbonate.In one embodiment, described second gegenion class material is calcium carbonate.

In some embodiments, comprise can neutralizing acid and/or affect the gegenion class material of bacterial metabolism occurred on an oral surface for oral cavity composition of the present invention.In some embodiments, described gegenion class material can reduce demineralization.In some embodiments, described gegenion class material is phosphate radical, by providing surface murder by poisoning and the orthophosphate by being hydrolyzed to the solubilising being suppressed tooth enamel by mass action on tooth enamel, can reduce tooth demineralisation.

In some embodiments, described gegenion class material is for providing carbonate or the bicarbonate radical of cushioning effect, and this cushioning effect reduces the amount that can be used for the acid in dental plaque and on tooth surfaces of dissolving tooth mineral matter.In some embodiments, by keeping pH close to the optimum pH by Plaque bacteria degraded guanidine, described carbonate or bicarbonate radical gegenion class material strengthen the sour Neutralization effect of polyguanidine compound.By many antibacterials as the source of nitrogen-containing compound and metabolism guanidine.Guanidine ruptures, and causes producing ammonia as by-product, and ammonia also contributes to acid neutralization and keeps higher pH level.In some embodiments, described carbonate or bicarbonate radical gegenion class material keep the level of pH to pH6.0 to pH9.0.In one embodiment, the pH of described oral cavity composition is in pH7.0 to pH8.0 scope.In some embodiments, when acid is neutralized, described carbonate or bicarbonate radical gegenion class material reduce the concentration of carbon dioxide.

C. carrier

Acceptable oral carriers comprises the oral delivery systems of any routine, such as dental care products, food and chewing gum.The example of dental care products can include but not limited to the collutory of dentifrice, topical solutions or paste, liquid preparation or spray or slurry form, powder, gel or tablet and dental floss.The example that can contain the food of oral cavity composition as herein described includes but not limited to dragee and confection.

In some embodiments, oral cavity composition of the present invention can containing the composition for any routine of concrete oral carriers known to persons of ordinary skill in the art.Such as, liquid mouthwash can contain solvent, such as distilled water or deionized water, ethanol etc.; Sweeting agent, such as glucide, aspartame etc.; And correctives, such as Oleum menthae, Herba Menthae Rotundifoliae wet goods.Dentifrice paste or gel can contain such as water, glycerol or Sorbitol; Conventional grinding agent, such as calcium pyrophosphate, aluminium hydroxide, resin, insoluble alkali metal metaphosphate etc.; Binding agent, such as hydroxyethyl-cellulose, xanthan gum, sodium carboxymethyl cellulose etc.; Foaming agent, such as sodium lauryl sulphate, sodium cocoglyceryl one acid esters sodium sulfonate, N-methyl-N-palmityl taurine sodium etc.; Correctives; Sweeting agent; Antiseptic and any other composition needed for concrete preparation.Dentifrice powder can containing conventional grinding agent and correctives.Tablet and powder can contain such as vehicle, such as lactose, mannitol etc.; Binding agent, such as corn starch, carboxymethyl cellulose etc.; And disintegrating agent.

Can be better simply compositions for topical application to the dentifrice of sensitive teeth position (the breech cementum of root surface that such as oral cavity exposes) or paste, and use with soft applicator.Such dentifrice or paste can contain or can be free of conventional grinding agent, foaming agent and correctives.Localization position (such as, for Dental Erosion, making the dentine after tooth) also relate to better simply compositions, and comprise for any other composition needed for the filler of dental pulp shutoff, cavity lining and cement and compositions well known by persons skilled in the art.Such as, zinc oxide and eugenol are applicable to tooth cements compositions.

D. excipient

In some embodiments, polyguanidine compositions of the present invention also can comprise at least one excipient.Described excipient is optional adaptive for any chemistry grouping of the present invention or the compound of classification.

In some embodiments, oral cavity composition of the present invention also comprises calcium salt.In some embodiments, described calcium salt is selected from: calcium carbonate, one-lime phosphate, dicalcium phosphate, tricalcium phosphate, calcium fluoride, MFP calcium, calcium pyrophosphate sodium, calcium laurate, calcium palmitate, and their combination.In one embodiment, described calcium salt is calcium carbonate.In some embodiments, described calcium salt produces calcium hydroxide, makes tooth enamel remineralization.In some embodiments, described calcium salt is calcium fluoride.In some embodiments, oral cavity composition of the present invention comprises the calcium fluoride for the treatment of effective dose.

In some embodiments, oral cavity composition of the present invention also comprises phosphorus source.In some embodiments, described phosphorus source is be selected from following phytate or phytic acid: inositoltriphosphoric acid salt (IP3), inositol tetrakisphosphate salt (IP4), IP5 salt (IP5), phytate (IP6), and their combination.These compounds contain multiple phosphate groups, and result can form ionic bridge with cation.

In some embodiments, the oral cavity composition of the present invention comprising polyguanidine compound and bicarbonate radical gegenion class material also comprises calcium carbonate and phytate.In some embodiments, comprise polyguanidine compound and bicarbonate radical gegenion class material, and the described oral cavity composition comprising calcium carbonate and phytate prevents pH from declining by the buffer capacity of bicarbonate radical and carbanion.Multiple bicarbonate radical gegenion can be carried in each chain of polyguanidine compound of the present invention, neutralize for acid.Guanidine first the large pKa value of group can stablize bicarbonate radical gegenion class material.Bicarbonate and carbonate can neutralize this acidic by-products with the acidic by-products direct reaction from carbohydrate fermentation product produced by antibacterial dental plaque subsequently.The pH scope of this rising suppresses the formation of dental caries and facilitates remineralization by the existence of calcium ion.

In some embodiments, described polyguanidine compound, calcium carbonate and phytate also can interact, to form complex compound.In some embodiments, described polyguanidine compound and calcium carbonate can with phytate bonding, to form calcium guanidine phytic acid root complex.In some embodiments, by being used in Ca ²⁺and guanidine form the phytate of ionic bridge between polycation, help of the present invention based on combining in the oral cavity composition of polyguanidine and sending Ca ²⁺ion.

iI. other compositions in the present compositions

In certain embodiments, the present invention can comprise the conventional any other additive for dentifrice formulation.Any suitable additive of any suitable amount or form can be used.Include but not limited to for suitable additive of the present invention: surfactant, desensitizer (comprising potassium salt), fluorine source, brightening agent, tartar control agents, antibacterial, grinding agent (comprising silicon dioxide), binding agent, thickening agent, detergent, adhesive agent, foam modifier, pH adjusting agent, taste agent, sweeting agent, correctives, coloring agent, antiseptic, their combination etc.It should be understood that these additives are optional component, and can individually or jointly be excluded in automatization of the present invention and wash dish compositions.Although it will also be appreciated that the universal performance of each in the material of above classification can be different, some common denominators can be there are, and in two or more in the material of these classifications, any given material can be used as multiple object.In certain embodiments, select other compositions of this kind of additive and bioactivity glass and compositions compatible.

A. surfactant

Be applicable to surfactant of the present invention include but not limited to: anion surfactant, non-ionic surface active agent, cationic surfactant, both sexes (amphoteric) surfactant, both sexes (ampholytic) surfactant, zwitterionic surfactant, with their mixture, as known to persons of ordinary skill in the art.Suitable surfactant can any suitable amount or form add, and optionally in surfactant system, and can add the character providing any expectation, includes but not limited to clean and/or foam properties.Suitable surfactant can comprise anion, cation, nonionic and amphoteric surfactant.

In one embodiment, compositions of the present invention comprises at least one surfactant.In one embodiment, the compositions comprising at least one surfactant comprises sodium lauryl sulphate.In one embodiment, compositions comprises the sodium lauryl sulphate that its amount is 0.5% weight-10% weight.In one embodiment, compositions comprises the sodium lauryl sulphate that its amount is 1% weight-5% weight.In one embodiment, compositions comprises the sodium lauryl sulphate that its amount is 1.5% weight-2% weight.

In one embodiment, the Dentrifice composition of the present invention comprising at least one surfactant comprises poloxamer.In one embodiment, the compositions comprising poloxamer comprises ethylene oxide/propylene oxide copolymer.In one embodiment, the compositions comprising poloxamer comprises the ethylene oxide/propylene oxide copolymer that its amount is 1.0% weight-45.0% weight.In one embodiment, the compositions comprising poloxamer comprises the ethylene oxide/propylene oxide copolymer that its amount is 5.0% weight-35.0% weight.In one embodiment, the compositions comprising poloxamer comprises the ethylene oxide/propylene oxide copolymer that its amount is 10.0% weight-25.0% weight.

B. tartar control agents

In some embodiments, compositions of the present invention optionally can comprise tartar and control (anti-dental calculus) agent, prepares the effect that this tartar control agents does not affect bioactivity glass detailed in this article and/or potassium salt.In herein useful those, tartar control agents comprises the salt of any one in these reagent following, such as their alkali metal salt and ammonium salt: phosphate and Quadrafos are (such as, pyrophosphate), poly-aminopropanesulfonic acid (AMPS), polyolefm sulfonates, polyolefin phosphates, diphosphate is azacycloparaffin-2 such as, 2-diphosphate (such as, azepan-2, 2-di 2 ethylhexyl phosphonic acid), N-methyl azacyclopentane-2, 3-di 2 ethylhexyl phosphonic acid, ethane-1-hydroxyl-1, 1-di 2 ethylhexyl phosphonic acid (EHDP), ethane-1-amino-1, 1-diphosphate and phosphino-alkanecarboxylic acid.Useful inorganic phosphate and Quadrafos comprise an alkali valency, bibasic and three alkali valency sodium phosphates, sodium tripolyphosphate, sodium tetrapolyphosphate, pyrophosphoric acid one sodium, disodium pyrophosphate, Sodium phosphate (Na3HP2O7), tetrasodium pyrophosphate, sodium trimetaphosphate, sodium hexameta phosphate, and their mixture.

C. fluoride sources

Be applicable to the reagent that fluoride sources of the present invention can comprise the acceptable granular fluoride ion in any oral cavity, prepare the effect that this reagent does not affect bioactivity glass, and this reagent such as can be used as anti-caries agent.Suitable fluorine source can include but not limited to: ionic fluorides, comprises alkali metal fluoride; Amine fluoride, such as olaflur (N '-octadecyltrimethylen-iamine-N, N, N '-three (2-ethanol)-dihydrofluoride); Stannous fluoride; Indium; With ion mono-fluor phosphate, comprise alkali metal mono-fluor phosphate such as potassium fluoride, sodium fluoride and ammonium fluoride and single fluorophosphoric acid potassium, sodium monofluorophosphate and single fluorophosphoric acid ammonium; With their mixture.

In one embodiment, Dentrifice composition of the present invention also comprises fluorine source.In one embodiment, compositions also comprises fluoride salt.In one embodiment, the compositions also comprising fluoride salt comprises sodium monofluorophosphate.In one embodiment, when fluoride sources is ion mono-fluor phosphate, optionally can add calcium glycerophosphate, show the activity that calcium glycerophosphate strengthens ion mono-fluor phosphate.In one embodiment, compositions can comprise the fluorine source provided between 100-3000ppm fluorion.In one embodiment, compositions can comprise the fluorine source provided between 500-2000ppm fluorion.

D. brightening agent

Be applicable to brightening agent of the present invention and can comprise the effective agent of any treatment being applicable to oral cavity.Suitable brightening agent includes but not limited to: titanium dioxide, hydrogen peroxide, sodium tripolyphosphate etc.In one embodiment, Dentrifice composition of the present invention also comprises brightening agent.In one embodiment, compositions of the present invention also comprises titanium dioxide.In one embodiment, suitable level titanium dioxide can be comprised.

E. grinding agent

Be applicable to grinding agent of the present invention and can comprise the acceptable granular grinding agent in any oral cavity, prepare this grinding agent not affect the effect of bioactivity glass.Can include but not limited to for suitable grinding agent of the present invention: silicon dioxide, zinc orthophosphate, sodium bicarbonate (sodium bicarbonate), plastic grain, aluminium oxide, hydrated alumina, calcium carbonate, calcium pyrophosphate, and their mixture.Described silica abrasive can be natural amorphous silica, comprises kieselguhr; Or the amorphous silica of synthesis, such as precipitated silica; Or silica gel, such as silica xerogel; Or their mixture.

Usually, the amount being applicable to the grinding agent of Dentrifice composition of the present invention is experimentally determined, according to technology well known in the art, to provide the clean of acceptable level and polishing.In one embodiment, Dentrifice composition of the present invention comprises grinding agent.In one embodiment, compositions comprises silica abrasive.In one embodiment, silica abrasive exists with the amount of 1% weight-30% weight.In one embodiment, silica abrasive exists with the amount of 5% weight-15% weight.In one embodiment, silica abrasive exists with the amount of 7% weight-10% weight.

F. taste agent

Be applicable to give between operating period that taste agent of the present invention can be included in Dentrifice composition the quality of expectation or any form of other sensations or the acceptable material in any oral cavity of amount.Suitable taste agent can include but not limited to: the correctives, sweeting agent, saliva-stimulant etc. of dispersion.

Useful correctives comprises any material of the taste that can be used for enhancing composition or the mixture of material herein.The acceptable correctives that is natural or synthesis in any oral cavity can be used, such as taste masking oil, taste masking aldehyde, ester, alcohol, similar material, and their combination.Correctives comprises vanillin, Salvia japonica Thunb., origanum, parsley oil, Oleum Menthae Rotundifoliae, Oleum Cinnamomi, wintergreen oil (methyl salicylate), Oleum menthae, Oleum Caryophylli, laurel fat, Oleum Anisi Stellati, Eucalyptus oil, tangerine oil, fruit oil and essence, comprise derived from following those: Fructus Citri Limoniae, Fructus Citri tangerinae, Citrus aurantium Linn., Fructus Citri grandis, Fructus Pruni, Fructus Musae, Fructus Vitis viniferae, Fructus Mali pumilae, Fructus Fragariae Ananssae, Fructus Pruni pseudocerasi, Fructus Ananadis comosi etc., the spice derived by bean or pea and nut, such as coffee, cocoa powder, laughable class, Semen arachidis hypogaeae, Semen Armeniacae Amarum etc., absorption and the correctives encapsulated, and their mixture.Correctives is also included in mouth the composition providing fragrance and/or other sensory effects herein, comprises effect that is nice and cool or that heat.Such composition comprises menthol, menthyl acetate, menthyl lactate, Camphora, Eucalyptus oil, Eucalyptus alcohol, anethole, eugenol, Cortex cinnamomi japonici (Ramulus Cinnamomi), oxanone, α-ionone, acrylic guaiethol, thymol, linalool, benzaldehyde, cinnamic aldehyde, WS-3, N, 2,3-trimethyl-2-butanamide, 3-1-alkoxypropan in the Meng-1,2-glycol, cinnamic aldehyde glycerine acetal (CGA), methone glycerine acetal (MGA), and their mixture.One or more correctivess optionally exist with the total amount of 0.01%-5%, in multiple embodiments, optionally exist with the total amount of 0.05-2%, 0.1%-2.5% and 0.1-0.5%.

Useful sweeting agent comprises acceptable natural or artificial, the nutritious or apotrophic sweeting agent in oral cavity herein.Such sweeting agent comprises dextrose, dextrosan, sucrose, maltose, dextrin, dry Nulomoline, mannose, xylose, ribose, fructose, levulose, galactose, corn syrup (comprising high-fructose corn syrup and corn-syrup solids), the starch of partial hydrolysis, hydrogenated starch hydrolysates, Sorbitol, mannitol, xylitol, maltose alcohol, dextrinose, aspartame, neotame, glucide and salt thereof, sucralose, based on the intense sweetness agent of dipeptides, ring is sulfonate (cyclamates), dihydrochalcone, with their mixture.One or more sweeting agents optionally with strongly depend on selected concrete sweeting agent total amount exist, but usually at 0.005%-5%, the level of optional 0.01%-1%.

Compositions of the present invention optionally can comprise saliva stimulant, prepares this stimulant not affect the effect of bioactivity glass detailed in this article and/or potassium salt, such as, can be used for improving xerostomia.One or more saliva stimulants optionally stimulate effective total amount to exist with saliva.

G. occlusive agent

Occlusive agent of the present invention includes but not limited to bioactivity glass, arginine/calcium carbonate, arginine bicarbonate/calcium carbonate and small particle silicas, or their combination.Term used herein " occlusive agent " refers to any reagent contributing to tooth or dental surface remineralization, or when be applied to dental tissue with prevention and/or repair defects in teeth time, the reagent of deposited compound on tooth surfaces and in dental surface.Such as, for the bioactivity glass of remineralization tooth, such as reactive amorphous calcium compound, comprises amorphous calcium phosphate, amorphous fluorinated calcium phosphate and amorphous calcium carbonate phosphate fluoride.When occlusive agent of the present invention is applied to dental tissue, prevention and/or reparation defects in teeth.

1. bioactivity glass

Compositions of the present invention comprises one or more biological acceptable bioactivity glass usually.

The inorganic glass materials that can form one deck hydroxy carbonate apatite according to the present invention is included but not limited to bioactivity glass for suitable biology of the present invention is acceptable.In one embodiment, Dentrifice composition of the present invention comprises biological activity and the acceptable glass of biology.In one embodiment, described compositions comprises phosphorus sodium calcium silicate.In one embodiment, described compositions comprises the phosphorus sodium calcium silicate that its amount is 1.0% weight-20% weight.In one embodiment, described compositions comprises the phosphorus sodium calcium silicate that its amount is 5.0% weight-15% weight.In one embodiment, described compositions comprises the phosphorus sodium calcium silicate that its amount is 10% weight.

Suitable biology is acceptable can have following composition with bioactivity glass, comprising: the silicon dioxide (SiO of 40% weight-86% weight ₂); Sodium oxide (the Na of 0% weight-35% weight ₂o); The calcium oxide (CaO) of 4% weight-46% weight; With the phosphorous oxide (P of 1% weight-15% weight ₂o ₅).Preferably, described biology is acceptable comprises with bioactivity glass: the silicon dioxide (SiO of 40% weight-60% weight ₂); Sodium oxide (the Na of 10% weight-30% weight ₂o); The calcium oxide (CaO) of 10% weight-30% weight; With the phosphorous oxide (P of 2% weight-8% weight ₂o ₅).Described oxide can be used as solid solution or mixed oxide or hopcalite to be existed.Be applicable to the acceptable and bioactivity glass of exemplary bio of the present invention comprise it forms the calcium oxide of silicon dioxide, the sodium oxide of 24.5% weight, the phosphorous oxide of 6% weight and 24.5% weight comprising 45% weight.

In one embodiment, except the oxide of silicon, sodium, phosphorus and calcium, suitable biology is acceptable also can be comprised with composition that is bioactivity glass: CaF ₂, B ₂o ₃, Al ₂o ₃, MgO and K ₂o.In certain embodiments, CaF ₂scope be 0% weight-25% weight.B ₂o ₃preferred scope be 0% weight-10% weight.Al ₂o ₃preferred scope be 0% weight-4% weight.The preferred scope of MgO is 0% weight-5% weight.K ₂the preferred scope of O is 0% weight-8% weight.

Biological " effectively " amount that is acceptable and bioactivity glass is the amount being enough to have the treatment of expectation or preventive effect in the people giving active substance or lower animal experimenter and not having excessive disadvantageous side effect (such as toxicity, stimulation or irritatedly to respond), when using in the manner of the present invention, match with rational income/Hazard ratio.Concrete effective dose becomes along with such as following factor: the concrete disease be treated, the physical qualification of experimenter, the character of simultaneously carrying out treating (if any), concrete active substance, concrete dosage form, the carrier of employing and the dosage of expectation used.

Bioactivity glass of the present invention provides effective material and tooth structure to interact.Biocompatible glass of the present invention is the biocompatible glass that can not trigger disadvantageous immune response.

According to the present invention, find, the bioactivity glass with specified particle diameter can be used in particular for treating above-mentioned disease.Particularly, by wherein little being obtained unexpected result with the compositions of the present invention of very little granule combination.In certain embodiments, such as, the bioactivity glass part of compositions comprises the little granule that can bond with tooth structure (such as, be less than 90 microns), and with less granule (such as, be less than 10) combinationally use, larger adhering to tooth structure and be used as ion reservoir in these granules, and less entering and block the irregular inside of multiple dental structure surface.

In one embodiment, the bioactivity glass that the acceptable and bioactivity glass of biology of the present invention is granular non-interconnected is applicable to.In one embodiment, the particle size range of described glass is less than 90 μm.In one embodiment, the particle size range of described glass is less than 70 μm.In one embodiment, the particle size range of described glass is less than 50 μm.In one embodiment, the particle size range of described glass is less than 40 μm.In one embodiment, the particle size range of described glass is less than 30 μm.In one embodiment, the particle size range of described glass is less than 20 μm.In certain embodiments, the particle diameter of the bioactivity glass part of described compositions is less than 20,10,5,4,3,2,1 microns.

In certain embodiments, in these granules larger (such as, be less than 90 microns to being less than 20 microns) other calcium and the reservoir of phosphorus are provided, the deposition of the calcium phosphate making to continue mineralising or started by little granule (such as, being less than 20 microns to being less than 1 micron).In certain embodiments of the invention, other calcium and phosphorus can by leaching to all tooth structures and granules, these granules be connected to the surface imperfection place of tooth structure inside or such as, at its opening, dential canaliculi.This so provide and continue whole reaction and continue the growth of the less granule in these granules, they block on the inside or opening at this surface imperfection place, and can cause effectively coating or fill surface imperfection place.Because less granule to use up their ion fast due to their higher surface areas, the calcium of this excessive concentrations and the ion of phosphorus make less the reacting in these granules.Their ion will be reacted and discharged to larger in these granules more lentamente due to longer effect.In addition, the dental surface opening at the larger irregular place of mechanical wear kinds of surface in these granules, makes little granule enter and reacts with surface imperfection place.

This effect is highly profitable for multiple application.Such as, in caries prevention or decay, compositions of the present invention can penetrate into the minimum depths at surface imperfection place, and accepts the ion without interruption from neighbouring larger particles, makes to grow after the ion supply of the storage that has it all.This is also very useful in sealing pit and crack, and obtains more effective and longer lasting sealing.

These tubules inaccessible cause such as after periodontal surgery, significantly reducing responsive amount.In certain embodiments, diameter is used to be less than 2 microns and to be greater than the mixture of the granule of 45 microns.Find, this combination obtains effective especially compositions.

In certain embodiments, described biology is acceptable comprises glass composition with bioactivity glass, and such composition comprises following component, by weight:

Composition	% weight
		SiO ₂	40-60
CaO ₂	10-30
		Na ₂O	10-35
P ₂O ₅	2-8
		CaF ₂	0-25

B ₂O ₃

0-10

In certain embodiments, below form (by weight percentage) and form bioactivity glass:

Composition	% weight
		SiO ₂	40-60
CaO ₂	10-30
		Na ₂O	10-35
P ₂O ₅	2-8
		CaF ₂	0-25
B ₂O ₃	0-10
		K ₂O	0-8
MgO	0-5

In multiple embodiments, described bioactivity glass is present in described compositions with the amount of 1% weight-35% weight, 5% weight-30% weight, 10% weight-25% weight, 15% weight-20% weight and 20% weight.

2. arginine bicarbonate/calcium carbonate

In certain embodiments, described occlusive agent comprises the granule of arginine bicarbonate, amino acid complex and calcium carbonate.In certain embodiments, arginine bicarbonate/calcium carbonate is grinding agent.In certain embodiments, described arginine bicarbonate/compound of calcium carbonate produces alkaline environment, connects to strengthen granule further.

In certain embodiments, described arginine-bicarbonate/calcium carbonate composition can resist tooth mineral matter and loses in dental caries and dentin hypersensitiveness.In other embodiments, these arginine-bicarbonates/calcium carbonate composition energy neutralizing acid produces and makes tooth structure remineralization.

In multiple embodiments, described arginine bicarbonate/calcium carbonate is present in described compositions with the amount of 1% weight-35% weight, 5% weight-30% weight, 10% weight-25% weight, 15% weight-20% weight and 20% weight.

3. small particle silicas

In certain embodiments, described occlusive agent comprises silicon dioxide, in some embodiment, is small particle silicas.The compound restorative material being widely used in tooth field in recent years needs to have following character.In certain embodiments, it is 0.01 μm-100 μm, 0.1 μm-50 μm, 1 μm-10 μm and 5 μm that described small particle silicas comprises mean diameter, or the ultra-fine grain of their combination.

In addition, there is small particle silicas and be used as pH buffer agent, make the pH scope of preparation according to the ISO standard, and provide increase inaccessible benefit.When with before consumer compare with clinical trial reference product, external retentivity and dentine electrical conductivity research display significantly improve retentivity, reduce dentine fluid flow and acid resistance.

In multiple embodiments, described small particle silicas is present in described compositions with the amount of 1% weight-35% weight, 5% weight-30% weight, 10% weight-25% weight, 15% weight-20% weight and 20% weight.

H. other active substances

In some embodiments, compositions of the present invention can optionally comprise other active materials, can be effective to prevention or the treatment sclerous tissues in oral cavity or the disease of soft tissue or disease, or prevention or treatment physiological disorder or disease.In some embodiments, described active substance is " systemic activity material ", and it can be effective to treat or prevention is not the disease of oral condition going up in whole or in part.In some embodiments, described active substance is " oral care active ", and it can be effective to treat or prevention disease or provide cosmetic benefit in oral cavity (such as, other sclerous tissueses in tooth, gingiva or oral cavity or soft tissue).Useful oral care active comprises brightening agent, caries preventive agent, tartar control agents, preventing dental plaque agent, periodontal actives, grinding agent, flavorants, tooth desensitizers, saliva stimulant herein, and their combination.

In some embodiments, compositions of the present invention optionally can comprise antibacterial, prepares this antibacterial not affect the effect of bioactivity glass detailed in this article and/or potassium salt.The example of antibacterial includes but not limited to triclosan, cetylpyridinium chloride with their combination.

In some embodiments, compositions of the present invention comprises nutrient substance, prepares this nutrient substance not affect the effect of bioactivity glass detailed in this article and/or potassium salt.Suitable nutrient substance comprises vitamin, mineral, aminoacid, and their mixture.Vitamin comprises vitamin C and D, vitamin B1, riboflavin, calcium pantothenate, nicotinic acid, folic acid, nicotiamide, vitamin B6, vitamin B12, para-amino benzoic acid, bioflavonoids, and their mixture.Supplementary comprises aminoacid (such as L-Trp, 1B, methionine, threonine, levocarnitine and L-BETAIN), lipotropic (such as choline, inositol, betanin and linoleic acid), and their mixture.

In some embodiments, compositions of the present invention also can contain antistain agent.Suitable antistain agent can include but not limited to: carboxylic acid, amino carboxylate compounds, phosphino-acetic acid, polyvinyl pyrrolidone etc.Described antistain agent can be joined in Dentrifice composition, or can be used as independent compositions and provide, use after dentifrice.

In some embodiments, compositions of the present invention also can comprise the material strengthening bio-vitric and the sedimental surface deposition/retentivity of any obtained HAP, include but not limited to Gantrez, enamel matrix, milk protein (casein), chitosan, pluracareL1220 (ethylene oxide/propylene oxide copolymer), poly(ethylene oxide), PVP, methacrylate, Lac, arginine, and their combination.

III. for the preparation of the method for the oral cavity composition containing polyguanidine compound

By any mode known to persons of ordinary skill in the art, by the modification of polyamine, the synthesis of polyguanidine compound can be realized.Under the aqueous conditions of gentleness, primary amine moiety can be completed expeditiously to guanidine the conversion of group.In some embodiments, first the method for the preparation of oral cavity composition of the present invention comprises the polymer selecting at least one containing primary amine, as illustrational in flow process 1.

In some embodiments, the described polymer containing primary amine is chitosan, PAH, polyvinylamine, poly-aminoalkyl acrylamide, polyvinyl imidazol, poly-aminoalkyl (methyl) acrylate, polymine, polylysine, poly ornithine compound, and their combination.In some embodiments, next comprise for the preparation of the method for oral cavity composition of the present invention primary amine moiety is on the polymer converted into guanidine group.

In some embodiments, then the method for the preparation of oral cavity composition of the present invention comprises with certain amount, and at the poly-guanidine of formation under the condition of gegenion complex, use the titration of gegenion solution.In some embodiments, the method for the preparation of oral cavity composition of the present invention also comprises with certain amount, and gathers guanidine at formation calcium under the condition of gegenion complex, with guanidine poly-described in the titration of calcium source gegenion complex.

IV. for preventing or treat the method for periodontal disease and dental caries

The present invention also comprises the method for preventing or treat periodontal disease and dental caries, and described method comprises the oral cavity composition containing polyguanidine compound of delivery treatments effective dose in oral cavity.The treatment effective dose of the oral cavity composition defined by the present invention used herein is the amount preventing or treat the oral cavity composition of periodontal disease and dental caries.In some embodiments, the amount of acid of effective dose for reducing or neutralize the dental plaque that caused by carbohydrate metabolism and produce is treated.In some embodiments, treatment effective dose is by mass action or by being conducive to remineralization, by the solubilising providing calcium to suppress tooth, can reduce the amount of tooth enamel, dentine and cemental demineralization.In some embodiments, by oral cavity composition oral administration of the present invention, and can not go calcification or destroy tooth enamel in addition.

In some embodiments, the method for active component targeting oral epithelium tissue is comprised the oral cavity composition of the present invention of delivery treatments effective dose in oral cavity.In some embodiments, the method for long antibacterial material or sterilization material is kept to comprise the oral cavity composition of the present invention of delivery treatments effective dose in oral cavity after being deposited on brush or rinsing on an oral surface.In some embodiments, the method for delay or prophylaxis of teeth dental caries comprises the oral cavity composition of the present invention of delivery treatments effective dose in oral cavity.In some embodiments, the method for the treatment of or prevention odontohyperesthesia comprises the oral cavity composition of the present invention of delivery treatments effective dose in oral cavity.

In yet another aspect, treat, reduce or prevent the method for odontohyperesthesia to comprise the oral cavity composition of the present invention of delivery treatments effective dose in oral cavity, make compositions contact the surface of tooth, a part of compositions can be incorporated in the opening of dential canaliculi by its mode.In one embodiment, part compositions enters dential canaliculi, and the described compositions wherein having entered tubule effectively blocks (that is, " obturation ") tubule, make Cucumber, mineral, ion, compound etc. by being suppressed or strengthening, cause desensitizing dental.In some embodiments, the method blocking dential canaliculi comprises the oral cavity composition of the present invention of delivery treatments effective dose in oral cavity.In some embodiments, the method for the treatment of carious lesions comprises the oral cavity composition of the present invention of delivery treatments effective dose in oral cavity.In some embodiments, the method for the pulp calcification of exposure is made to comprise the oral cavity composition of the present invention of delivery treatments effective dose in oral cavity.In some embodiments, the method for the pit of tooth or the substrate in crack or all calcifications is made to comprise the oral cavity composition of the present invention of delivery treatments effective dose in oral cavity.

Embodiment

Embodiment 1

The single tube tooth paste product comprising occlusive agent and potassium salt that excellent sensitivity of tooth is alleviated is provided

Exemplary of the present invention comprises the single tube tooth paste product comprising one or more occlusive agents and one or more potassium salt.In an exemplary embodiment, in order to alleviate sooner, use single tube technology, quick occlusive agent such as biological activity and biology acceptable glass (such as, Novamin) and potassium be combined.Find to provide significant external obturation containing the not moisture biological activity of potassium and the acceptable glass formulation of biology.

In another exemplary embodiment, be surprised to find that, by adding commercially available small particle silicas (such as, SorbosilAC-43), described biological activity and the acceptable glass of biology (such as, Novamin) preparation have other inaccessible benefit.

Carry out external dose response research, to determine optimum biological activity inaccessible fast and the acceptable glass of biology (such as, Novamin) level.Preparation is containing the biological activity of 5%, 7.5% and 10% and the product of the acceptable glass of biology (such as, Novamin).By confocal microscope, after 6 times and 10 brushes, evaluate product.After 6 process, 10% biological activity and the significant obturation of the acceptable glass of biology (such as, Novamin) preparation display, and after 10 process, all biological activitys and the acceptable glass of biology (such as, Novamin) level provide significant obturation.See Fig. 1.

In order to improve 5% biological activity and the obturation of the acceptable glass of biology (such as, Novamin) when processing for 6 times, study the external impact adding silicon dioxide (such as, IneosAC43 silicon dioxide).As shown in the confocal microscope images in Fig. 1, add 9% silicon dioxide (such as, IneosAC43 silicon dioxide), significantly improve obturation when 6 process.

The acid resistance of in-vitro evaluation two kinds of leading systems.Dentine disk through 6 process is soaked 1 minute in CokeClassic.Image is shown in Fig. 2.Two kinds of systems all show significant acidproof attack.

Being separated with preventing to increase multiviscosisty, multiple glue being joined this not moisture preparation based on glycerol.In certain embodiments, carboxymethyl cellulose provides best overall mouthfeel.Carbopol (carbopol) provide multiviscosisty, but, give stickiness feeling in certain embodiments.By preparation optimization.All leading preparations are stablized 4 weeks at 40 DEG C.

10% Novamin/20%Pluraflo/CMC (without KCl)

10% Novamin/3.75%KCL/CMC

5% Novamin/3.75%KCL/9%AC43/CMC

Embodiment 2

Illustrate the conductivity data that 10% Novamin toothpaste contrasts with conventional non-blocking silicon dioxide toothpaste in table 1 below, the raising effect of confocal laser microscope image display Novamin dose response and AC43 silicon dioxide.Result is illustrated in Fig. 3.

Table 1: the electrical conductivity measured after by compositions-treated disclosed herein

The invention is not restricted to the scope of specific embodiment disclosed in an embodiment, these embodiments are intended to illustrate a few aspect of the present invention, and functionally equivalent any embodiment within the scope of the invention.In fact, except shown herein and describe those except, various amendment of the present invention be will become apparent to those skilled in the art that and will fall in the scope of claims.

For any list of references quoted, be attached to herein by reference and in full.

Claims

1. an oral cavity composition, described compositions comprises:

A. the polyguanidine compound of formula (I):

Wherein:

X represents the acceptable gegenion in oral cavity;

Z is CH or N;

R ₁, R ₂and R ₃be hydrogen or straight or branched, saturated or undersaturated optional hydroxylated C independently of one another ₁-C ₁₆alkyl;

A represents straight or branched, saturated or undersaturated optional hydroxylated C ₁-C ₁₆alkyl; Or A represents and is selected from by least one straight or branched, the saturated or undersaturated C that following group optionally replaces ₁-C ₁₆alkylidene: hydroxyl, carboxyl, carboxylate group or halogen; The optional alkylidene containing at least one functional group, at least one functional group described is selected from: amine, ether, thioether, ester, amide, carbamate, urea, by C ₁-C ₈the C that alkyl, hydroxyl or halogen optionally replace ₆aryl or C ₃-C ₈cycloalkyl ring; Or A represents one or more unsubstituted or by C ₁-C ₈the C of alkyl, hydroxyl or halogen substiuted ₆or C ₇aryl or C ₅-C ₇cycloalkyl ring; Or A represents C ₁₀-C ₁₄polyaryl or C ₆-C ₁₀multi-ring alkyl chain, it can be selected from following functional group interval by least one: C ₁-C ₈alkylidene, amine, amide, ether, thioether, hydrogen atom, carbamate or urea;

N represents between 2-5, the integer of 000; With

B. oral cavity acceptable carrier;

Preferred wherein said gegenion is bicarbonate radical (HCO ₃ ^-);

Preferred described compositions also comprises calcium salt;

Preferred described calcium salt is calcium carbonate, one-lime phosphate, dicalcium phosphate, tricalcium phosphate, calcium fluoride, MFP calcium, calcium pyrophosphate sodium, calcium laurate, calcium palmitate, and their combination;

Preferred described calcium salt is calcium carbonate;

Preferred described compositions also comprises phosphorus source;

Preferred described phosphorus source is be selected from following phytate or phytic acid: inositoltriphosphoric acid salt (IP3), inositol tetrakisphosphate salt (IP4), IP5 salt (IP5), phytate (IP6), and their combination;

Preferred described oral cavity composition is dental care products, food and chewing gum.

2. prepare a method for the oral cavity composition of claim 1, described method comprises:

A. select at least one containing the polymer of primary amine;

B. primary amine moiety is on the polymer converted into guanidine group; With

C. to form the amount of polyguanidine gegenion complex and under the condition forming polyguanidine gegenion complex, to use the titration of gegenion solution;

Preferably the described polymer containing primary amine is chitosan, PAH, polyvinylamine, poly-aminoalkyl acrylamide, polyvinyl imidazol, poly-aminoalkyl (methyl) acrylate, polymine, polylysine, poly ornithine compound, and their combination;

Preferred described gegenion solution is bicarbonate radical (HCO ₃ ^-) solution;

Preferred described polyguanidine gegenion complex is polyguanidine bicarbonate radical complex;

Preferred described method is further comprising the steps of: d. to form the amount of calcium polyguanidine gegenion complex, and under the condition forming calcium polyguanidine gegenion complex, with polyguanidine gegenion complex described in the titration of calcium source;

Preferred described complex is calcium polyguanidine bicarbonate radical complex;

Preferred described calcium source is calcium carbonate, one-lime phosphate, dicalcium phosphate, tricalcium phosphate, calcium fluoride, MFP calcium, calcium pyrophosphate sodium, calcium laurate, calcium palmitate, and their combination;

Preferred described calcium source is calcium carbonate.

3., by a method for active component targeting oral epithelium tissue, described method comprises the oral cavity composition of the claim 1 of delivery treatments effective dose in oral cavity.

4. retain a method for long antibacterial material or sterilization material after being deposited on brush or rinsing on an oral surface, described method comprises the oral cavity composition of the claim 1 of delivery treatments effective dose in oral cavity.

5. a method for delay or prophylaxis of teeth dental caries, described method comprises the oral cavity composition of the claim 1 of delivery treatments effective dose in oral cavity.

6. a method for treatment or prevention odontohyperesthesia, described method comprises the oral cavity composition of the claim 1 of delivery treatments effective dose in oral cavity.

7. block a method for dential canaliculi, described method comprises the oral cavity composition of the claim 1 of delivery treatments effective dose in oral cavity.

8. treat a method for carious lesions, described method comprises the oral cavity composition of the claim 1 of delivery treatments effective dose in oral cavity.

9. make a method for the pulp calcification of exposure, described method comprises the oral cavity composition of the claim 1 of delivery treatments effective dose in oral cavity.

10. make a method for the pit of tooth or the substrate in crack or all calcifications, described method comprises the oral cavity composition of the claim 1 of delivery treatments effective dose in oral cavity.