CN104069013A - Oral nursing stannous composition - Google Patents

Oral nursing stannous composition Download PDF

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Publication number
CN104069013A
CN104069013A CN201410208416.2A CN201410208416A CN104069013A CN 104069013 A CN104069013 A CN 104069013A CN 201410208416 A CN201410208416 A CN 201410208416A CN 104069013 A CN104069013 A CN 104069013A
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stannous
approximately
stannum
compositions
sub
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威廉姆·迈克尔·格兰多夫
小唐纳德·詹姆斯·怀特
阿里夫·A·拜格
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Procter and Gamble Ltd
Procter and Gamble Co
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Procter and Gamble Ltd
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Abstract

The invention discloses an oral composition containing a stannous ion source, a multivalent cation source and a mineral surface active agent; the composition provides the treatment effects of resisting microorganisms, inhibiting ozostomia, growth and metabolism of bacterial plaque, reducing gingivitis, retarding progress of periodontal disease and reducing dentin hypersensitivity and decayed teeth of dental crowns and tooth roots from stannous fluoride and/or other stannous salts; the mineral surface active agent is the reagent having substantivity to mineral surfaces, such as teeth, and chelating activity to the multivalent cations; the multivalent cations comprise stannous (Sn<+2>), zinc (Zn<+2>), copper (Cu<+2>), aluminium (Al<+3>), iron (Fe<+2>, Fe<+3>), strontium (Sr<+2>), calcium (Ca<+2>), barium (Ba<+2>), magnesium (Mg<+2>) and manganese (Mn<+2>); the mineral surface active agent is preferably the polymer or the copolymer containing a phosphate radical, a phosphonate radical or carboxyl; and the oral nursing stannous composition disclosed by the invention further comprises a fluorine ion source and can be prepared into a single-phase or double-phase composition.

Description

Sub-tin oral care composition
The application is to be the dividing an application of Chinese patent application 200680055850.5 on October 2nd, 2006 applying date.
Invention field
The oral cavity composition of the improvement that the present invention relates to comprise tin salt such as stannous fluoride.The compositions of these improvement has beneficial effect in the multiple oral cavity that is derived from stannous fluoride and/or other tin salt, comprises anti-microbial effect, suppresses halitosis, suppresses plaque growth and metabolism, minimizing gingivitis, slows down periodontal disease process, reduces dentine hypersensitivity and reduces corona and root of the tooth moth erosion and corroding.Except providing above-mentioned beneficial effect, described compositions also provides with the conventional composition that comprises sub-stannum and compares significant improvement, comprising: 1) reduced tooth discoloration degree; 2) reduce convergence, thereby improved the aesthetic feeling characteristic of compositions; 3) reduced the formation of dental calculus, and 4) strengthened stability, bioavailability, thus sub-stannum strengthened as the effect of antimicrobial, antiplaque agent and gingivitis agent.The compositions that comprises sub-stannum of improving provides these beneficial effects by the combination effect of sub-stannum, the second polyvalent cation and mineral surfaces active substance and chelating agen, described reagent is preferably polymer and comprises specifically anionic polymer, such as polyphosphate, polyphosphonate or the polycarboxylate of condensation.The invention still further relates to the method that strengthens therapeutic efficiency, reduces the desirable property of oral cavity composition aesthetic feeling that tooth discoloration and improvement comprise tin salt such as stannous fluoride simultaneously.
background of invention
Stannous fluoride because of its effect in being formulated into dental products known.Stannous fluoride because of its therapeutic efficiency aspect suppressing dental caries be once the first fluorine source being incorporated in toothpaste.After this, stannous fluoride gel, collutory and dentifrice show can provide the clinical efficacy that reduces super quick, the dental plaque of dental caries, dentine and gingivitis.Except these clinical efficacy, the preparation that comprises stannous fluoride also contributes to provide the breath freshening beneficial effect of improvement by chemistry and antibacterial action.Because sub-stannum is hidden between the storage life oxidation or precipitation is lost at frame, so stannous fluoride preparation generally includes stabilising system, and described stabilising system is intended to keep the Ya Xi of bioavailable (being solvable and active) content.Therefore, stannous fluoride preparation is prepared together with other composition that comprises sub-stannum, and this provides the sub-stannum of high concentration to lay in to keep clinical efficacy as sub-stannum.Regrettably,, although known stannous fluoride compositions is highly effective, due to the complexity of aspect the preparation research and development the abundant stability of stannous fluoride is provided and sub-stannum side effect aspect, be therefore difficult to obtain successful commercial exploitation.The preparation that provides effect to increase or improve causes that side effect increases conventionally.This has limited clinical and business application.
A side effect the most significant of the conventional application of stannous fluoride is that tooth becomes yellowish-brown.This variable color is that the reacting of sub-stannum of utilizing being deposited on dental surface during being processed with effective stannous fluoride preparation by thin film, dental plaque and diet component caused.
Second side effect that effectively stannous fluoride preparation meets with during use is conventionally worthless preparation convergence.Astringent is the protein precipitant of topical application, and its cell hypotonicity has limited the effect to cell surface and intercellular space.Strong convergence agent can impel tissue contracts and wrinkling, and mucus secretions may precipitate or reduce.In dental products, these chemical actions in oral cavity such as on tongue, gingival tissues or mouth epithelial cells, provide make us unhappy " being dried " sense.The sub-stannum preparation that comprises the enough sub-stannum that supplies biological utilisation is described as astringent conventionally by patient and consumer, and this characteristic is worthless.Convergence is the most remarkable after product is used.
With the 3rd side effect of stannous fluoride Dentrifice composition, be often by these compositionss, to reduce the reduction of the effect of dental calculus.Fixed, be proved effective antimicrobial, gingivitis and there is other stannous fluoride dentifrice of expecting beneficial effect and always dental calculus on worthless gum has not been gathered and prevents to show repeatably clinical effect.Suppressing gum upper tooth calculus and other clinical beneficial effect is that professional, patient and consumer are desired.The multifunction activity of oral cavity composition can make health care simplify, and the holistic approach that keeps therapeutic oral health is provided.
Early stage trial is researched and developed effectively and the acceptable stannous fluoride oral cavity composition of consumer attempts to solve the detriment that these gather, yet none obtains complete success.The United States Patent (USP) 5,004,597 of authorizing the people such as Majeti discloses the oral cavity composition that comprises stannous fluoride and gluconate.Comprise the sub-stannum of gluconic acid and can improve preparation effect and stability.Although effectively,, this preparation causes tooth that the variable color of inadvisable degree occurs.In addition, described preparation has and is mainly derived from the constringent unacceptable aesthetic feeling of sub-stannum.Equally, the United States Patent (USP) 5,578,293 of authorizing the people such as Prencipe discloses organic acid compound in the purposes of stablizing in stannous ion concentration.Except stannous fluoride and as organic acid citrate, described preparation also comprises soluble pyrophosphate.The United States Patent (USP) 4,323,551 of authorizing the people such as Parran discloses with pyrophosphate anti-dental calculus beneficial effect is provided.Clinical research is definite, the potentiality of mineral anion surface active inhibitor such as pyrophosphate aspect the tooth discoloration development that prevents nature and antimicrobial to bring out.(Grossman, Bollmer, Sturzenberger and Vick; " Journal of Clinical Dentistry " 6 (4): 185-187,1995).In the people's such as Prencipe patent, all examples all comprise enough citric acids and/or two hydration sodium citrates to stablize stannous ion and to prevent precipitation.This tittle has also directly suppressed the combination of sub-stannum to pyrophosphate.If sub-stannum is combined with pyrophosphate really, studies have shown that, this will reduce the antimicrobial acivity of stannous fluoride.Effectively stablize stannous ion and in conjunction with required citrate amount, also significantly weakened the aesthetic feeling of sub-stannum compositions with opposing precipitation and opposing pyrophosphate.Described compositions will be sent out salty, turn sour, and the sub-stannum of being combined with citrate will have astringent character, and it is acceptable that this has reduced whole taste.The United States Patent (USP) 5,213,790 of authorizing the people such as Lukacovic also discloses the purposes of source of citrate ion in sub-stannum compositions.The United States Patent (USP) 5,780,015 of authorizing the people such as Fisher discloses the purposes of the biphase dentifrice that comprises potassium salt and tin salt, wherein uses castor oil hydrogenated to help reduce convergence.By stablizing tin salt with the organic acid compound described in people's patents such as Prencipe.Another trial of preparing effective sub-stannum compositions is described in the United States Patent (USP) 5,716,600 of authorizing the people such as Zahradnik.This patent discloses low water content preparation, and described low water content preparation contributes to prevent that stannous fluoride from degrading in time.The tooth discoloration of the low preparation of landing attempt not.
The United States Patent (USP) 5,017,363 of authorizing Suhonen discloses effectively stablizes the alkyl vinyl ether of stannous ion amount and the stannous ion chelating copolymer of maleic anhydride or maleic acid.Suhonen is also disclosed is, because the Stabilization of stannous ion chelate polymer under for example, existence at silicon dioxide, soluble phosphate such as soluble pyrophosphate (tetrasodium pyrophosphate and tetrapotassium pyrophosphate) and the compound that comprises aldehyde radical is invalid, therefore described compositions does not basically contain these compositions.
Authorize White, the people's such as Jr. United States Patent (USP) 5,338,537 discloses the purposes of low-molecular-weight di 2 ethylhexyl phosphonic acid, and described di 2 ethylhexyl phosphonic acid is used as the bonding agent of sub-stannum to contribute to reduce the variable color trend being caused by described compositions.Although can effectively reduce the probability of tooth discoloration, laboratory research confirms, and the antibacterial activity of the preparation that comprises the sub-stannum compound with low-molecular-weight di 2 ethylhexyl phosphonic acid is very low.In the situation that not there is not strong citrate chelation as above, the preparation that contains solubilized pyrophosphate has obtained similar result.
Described in above, find that the reduction of antibacterial/antiplaque activity and stannous fluoride stability and tooth discoloration probability may relate to identical chemistry and biochemistry binding site.Therefore,, in order to obtain the reduction of stability and/or tooth discoloration, may damage antibacterial/antiplaque active.This makes to be difficult to research and develop best stannous fluoride oral cavity composition, and why now to have explained only there is a small amount of stannous fluoride compositions on market.In order to improve consumer for acceptability and the compliance of the use of the oral cavity composition that comprises sub-stannum, need a kind of high effect but tooth discoloration degree and the lower sub-stannum compositions of other negative aesthetic such as convergence.In addition, wish these preparations in minimizing and suppress to provide synchronous effect aspect dental calculus formation.
summary of the invention
The present invention relates to comprise stannous ion source, polyvalent cation source and in conjunction with the oral cavity composition of the mineral surface active agent of sub-stannum, described compositions provides the therapeutic efficiency of enhancing, has minimum tooth discoloration and convergence side effect simultaneously.Described compositions provides minimizing and the inhibitory action of dental calculus on gum simultaneously.Described mineral surface active agent is to the direct reagent of mineral surfaces such as tooth, and has the sequestering activity to polyvalent cation, such as sub-stannum (Sn + 2), zinc (Zn + 2), copper (Cu + 2), aluminum (Al + 3), ferrum (Fe + 2, Fe + 3), strontium (Sr + 2), calcium (Ca + 2), barium (Ba + 2), magnesium (Mg + 2) and manganese (Mn + 2).Described compositions also can comprise fluorine ion source.Oral care composition of the present invention can be formulated into single-phase or two-phase compositions.The present invention also provides by use the method that stable Dentrifice composition is sent the compositions that comprises sub-stannum effectively to experimenter, and described compositions has minimum tooth discoloration or convergence side effect, and has effective tartar inhibitory action.The combination in the stannous fluoride that described compositions comprises clinical effective and/or other tin salt and mineral surface active agent (polymer that preferably comprises phosphate radical, phosphonate radical or carboxyl) and polyvalent cation source.
For a person skilled in the art, by detailed description below, these and other feature, aspect and advantage of the present invention will become apparent.
detailed Description Of The Invention
Although provide after description, particularly point out and claimed claims of the present invention clearly, the present invention may be better understood to it is believed that description by below.
Except as otherwise noted, all percentage ratio used herein is all by the weighing scale of described Dentrifice composition.Except as otherwise noted, ratio used herein is the mol ratio of total composition.Except as otherwise noted, all measurements are all carried out 25 ℃ of temperature.
Herein, " comprise/comprise " and refer to add and do not affect other step of final result and other composition.This term comprise term " by ... form " and " substantially by ... composition ".
As used herein, word " comprises/comprises " and its variant is intended to non-limitingly, makes the narration of list discal patch object not get rid of the similar entry that other also may be useful in material of the present invention, compositions, apparatus and method.
As used herein, word " preferably ", " preferably " and their variant refer to embodiment of the present invention that specific beneficial effect can be provided under specific environment.Yet other embodiment can be also preferred under identical or other environment.In addition, the detailed description of one or more preferred embodiments does not represent that other embodiment is useless, and is not intended to get rid of other embodiment in category of the present invention.
Oral cavity composition of the present invention can be toothpaste, dentifrice, dentifrice, local by buccal cavity gel, collutory, artificial tooth product, mouth spraying agent, medicine caked sugar, buccal or gum formats.
Except as otherwise noted, as used herein, term " dentifrice " refers to paste, gel or liquid preparation.Dentrifice composition can be any desired form, as dark striped, shallow striped, multilamellar, paste have gel or their combination in any around.
Described oral cavity composition can be single-phase oral cavity composition, can be maybe every kind of combination that is arranged in independent two or more oral cavity compositions mutually.Herein, " single-phase or independent phase " refers to all components of every kind of compositions is mixed in a kind of mixture, and described mixture can comprise liquid, solid and gas component.Therefore, every can be uniform or heterogeneous mutually.Described " oral cavity composition " refers to following product, it is not deliberately swallowed the whole body administration for particular therapeutic agent in general application, but in oral cavity, retains the sufficiently long time substantially to contact all dental surfaces and/or oral cavity tissue to have orally active.As used herein, term " total composition " refers to the total composition that is delivered to oral cavity, and no matter it comprises single-phase or heterogeneous.
If expect biphase oral cavity composition, each oral cavity composition is included in the compartment of physical separation of allotter, distribute side by side.As used herein, term " allotter " refers to any pump, pipe or the container that is applicable to dispensing toothpaste.
As used herein, term " oral area acceptable carrier " comprises for the safety of the present composition and effective material.Above-mentioned substance is the conventional additives in oral care composition, includes but not limited to fluorine ion source, anti-dental calculus or anticalculus agent, buffer agent, grinding agent such as silicon dioxide, bleach such as peroxide source, alkali metal hydrogencarbonate, thickening material, wetting agent, water, surfactant, titanium dioxide, flavor system, sweeting agent, xylitol, coloring agent and their mixture.
Herein, term " tartar " and " dental calculus " are used interchangeably, and refer to the dental plaque biofilm mineralizing.
Ya Xi as used herein, term " Ya Xi " is defined as being arranged in dentifrice or other dental products and provides such as the tin salt that comprises stannous fluoride via source.It can relate to by the stannous ion providing for stablizing the tin salt that is different from stannous fluoride that object adds.
Can be used for active component of the present invention and other composition can classify or describe according to effect or the operational mode of its beauty treatment and/or treatment beneficial effect or its supposition.Yet should be appreciated that in some cases, can be used for beauty treatment and/or treatment beneficial effect or effect that active substance of the present invention and other composition can provide more than one, or work or move by more than one model of action.Therefore, classification herein just for convenience's sake, is not intended to composition to be limited in the listed application particularly pointing out or several application.
The present invention relates to oral cavity composition, described oral cavity composition comprises stannous ion source, be different from the polyvalent cation source of sub-stannum and mineral surface active agent Ya Xi and polyvalent cation to sequestering activity, described compositions provides the therapeutic efficiency of the enhancing that is derived from sub-stannum, has minimum tooth discoloration and convergence side effect simultaneously.Herein, " be derived from the therapeutic efficiency of sub-stannum " and be intended to comprise antimicrobial efficacy, halitosis inhibition, plaque growth and metabolic inhibition, minimizing gingivitis, slow down periodontal disease process and reduce dentine super quick.Described compositions preferably comprises fluoride source, and it can be stannous fluoride, other fluoride salt or their combination.Described compositions provides minimizing and the inhibitory action of dental calculus on gum simultaneously.Tooth discoloration and constringent reduction also can, via suitable and deposit preparation and be enhanced, comprise and use suitable poloxamer composition.
Described mineral surface active agent (MSA) is preferably polymer, in particular to anionic polymer, such as average chain length, is approximately 4 or more polyphosphate, polyphosphonate or other polymer that comprises phosphate radical or phosphonate radical or carboxyl.Those of ordinary skills can be susceptible to, polymeric binders such as average chain length be approximately 4 or more polyphosphate in the dentifrice system that comprises sub-stannum, will have with pyrophosphate or tripolyphosphate and similarly act on.Find, in order to prevent mottle from producing, adopt pyrophosphate, diphosphate or tripolyphosphate to come chemical bond or the sub-stannum of chelating can cause equally unacceptable treatment loss of energy potential.Yet, use compared with the polyphosphate of long-chain and other polymer that comprises phosphate radical or phosphonate radical and can produce beyond thought effect, because they can reduce the side effect of tooth discoloration and generation convergence, and can significantly not reduce the effect of sub-stannum.In fact find, compare with the prior art compositions of stabilizing agent such as citrate with comprising separately stannous fluoride or comprise stannous fluoride, in the oral cavity composition that comprises tin salt such as stannous fluoride, comprising these polymer mineral surface active agent can provide significant therapeutic efficiency and reduce tooth discoloration and degree of convergence, reduces dental calculus on gum simultaneously.
Oral care composition of the present invention can be formulated into single-phase or two-phase compositions.One embodiment of the invention provide a kind of biphase oral cavity composition, and described compositions comprises first compositions in the polyvalent metal ion source (preferably zinc) that comprises stannous ion source and be different from sub-stannum and the second compositions that comprises mineral surface active agent.Mineral surface active agent in this embodiment can be to have approximately 4 or the straight chain polyphosphate of more average chain length.The compositions that comprises polyphosphate preferably has approximately 20% limited water content at most, farthest to reduce the hydrolysis of polyphosphate.
Another embodiment of the invention relates to single-phase oral cavity composition, and described compositions comprises stannous ion source, be different from the polyvalent metal ion source of sub-stannum and mineral surface active agent such as average chain length is approximately 4 or more straight chain polyphosphate.Described single-phase composite is mixed with and makes described straight chain polyphosphate resistant to hydrolysis degraded stable.
The invention still further relates to single-phase or two-phase compositions, described compositions comprises stannous ion source, be different from the polyvalent metal ion source of sub-stannum and molecular weight is 500 or the larger anionic polymer that comprises a phosphonate radical, diphosphine acid group and carboxyl functional group or its combination.
The present invention also provides by use the method that stable Dentrifice composition is sent the compositions that comprises sub-stannum effectively to experimenter, described compositions has minimum tooth discoloration or convergence side effect, and there is effective tartar inhibitory action, the stannous fluoride that described compositions comprises clinical effective and/or other tin salt and the combination that is different from active and chelating agen such as the polymer that comprises phosphate radical or phosphonate radical of the polyvalent metal ion source of sub-stannum and mineral surfaces.A kind of delivering method of this improved stannous oral compositions through improving relates to uses the dentifrice that comprises two kinds of Dentrifice compositions, and described compositions is included in the compartment of physical separation.Another kind method relates to experimenter uses stable single phase dentifrice compositions.An embodiment of stable single-phase composite comprises polyphosphate or other anionic polymer that comprises phosphate radical or phosphonate radical, the stannous fluoride as stannous ion source, zinc ion source, wherein said compositions can have lower total water content, and this depends on the needs of stability.
A kind of preferred delivering method of the compositions that comprises sub-stannum through improving of the present invention relates to uses the dentifrice that comprises two kinds of Dentrifice compositions, and described compositions is contained in the compartment of physical separation.Physical separation makes each dentifrice phase and wherein composition is fully stable.When mixing use, the chemical interaction of the Ya Xi (from stannous fluoride and/or other tin salt) of a dentifrice in mutually and the isolation dentifrice mineral surface active agent in mutually can make two kinds of compositions suitably send, thereby provide complete therapeutic activity, and provide significant dental calculus to reduce effect, and significantly reduce tooth discoloration and the inadvisable side effect of convergence.The first Dentrifice composition will comprise stannous ion source, and the second Dentrifice composition preferably comprises polyphosphate or other anionic polymer that comprises phosphate radical, phosphonate radical, carboxyl or copolymer, or their mixture.According to the reciprocal action with other component, the polyvalent cation source that is different from sub-stannum can be incorporated in the first or second compositions or in these two.
Solvent in compositions of the present invention and optional components are described in following paragraph.
stannous ion source
The present invention comprises stannous ion source as a kind of solvent.Stannous ion is provided by the stannous fluoride and/or other tin salt that join in oral cavity composition.Find, stannous fluoride contributes to reduce dental caries, gingivitis, dental plaque and sensitivity, and contributes to provide breath freshening beneficial effect.The sub-stannum providing in oral cavity composition provides effect by the experimenter to the described compositions of use.Other tin salt comprises two hydrated stannous chlorides, stannous acetate, the sub-stannum of gluconic acid, stannous oxalate, stannous sulfate, the sub-stannum of lactic acid and stannous tartrate.Preferred stannous ion source is stannous fluoride and two hydrated stannous chlorides.The tin salt content mixing counts approximately 0.05% to approximately 11% by the weight of described total composition.Preferably, described tin salt content is approximately 0.1% to approximately 7%, more preferably from about 0.4% to approximately 3%.Preparation comprises in the total composition that stannous fluoride and other tin salt provide stannous ion conventionally approximately 3, and 000ppm is to approximately 15, the sub-stannum content within the scope of 000ppm.
The dentifrice that comprises tin salt, especially stannous fluoride and stannous chloride is described in the United States Patent (USP) 5,004,597 of authorizing the people such as Majeti.Other description of tin salt can be referring to the United States Patent (USP) 5,578,293 and the United States Patent (USP) 5,281,410 of authorizing the people such as Lukacovic of authorizing the people such as Prencipe.Except stannous ion source, also can comprise and stablize other required composition of sub-stannum, the composition described in people such as the people such as Majeti and Prencipe.
mineral surface active agent (MSA)
The present invention comprises mineral surface active agent, and described mineral surface active agent has substantivity to tooth, and Ya Xi and other polyvalent cation are had to chelating or combination activity.Herein, abbreviation " MSA " refers to this type of reagent." mineral " descriptor is intended to show that the surface activity of surfactant or substantivity are for mineral surfaces, such as calcium phosphate mineral or tooth.Preferred mineral surface active agent is polymer, and in particular to the polymer that comprises anionic group, described anionic group is selected from phosphate radical, phosphonate radical, carboxyl and their mixture.This type of anionic functional group provides and cation or the interactional ability of positively charged entity to these reagent.
These reagent demonstrate the affinity (specifically, by the chelation of stannous ion) in conjunction with sub-stannum, and this can pass through from stannous fluoride (SnF 2) in discharge fluorion and provide the fluorion form of increase to confirm when sub-stannum is combined.Effectively reagent also demonstrates the surface reaction to calcium phosphate mineral, thus the formation of expected delay dental calculus or tartar.Described reagent also can provide and suppress dental plaque, adjusting surface and anti-erosion beneficial effect.It is desirable to, these reagent are combined with sub-stannum, but the mixture that still can make combination provides desired tartar inhibitory action, dental plaque inhibitory action and surface modulation effect, and inhibition dental caries, oral malodor and periodontal disease (the comprising gingivitis) effect of stannous fluoride is not had to adverse influence.
The method of stable sub-stannum is provided with mineral surface active agent combination or the sub-stannum of chelating, especially in aqueous environment, its Central Asia stannum can form tin compound, or can from solution, be precipitated out, thereby reduce the content that can utilize stannous ion, therefore reduce the effect of described compositions.For example, in authorizing the United States Patent (USP) 5,017,363 of Suhonen, reported and can stablize stannous fluoride compositions with the copolymer of alkyl vinyl ether and maleic anhydride or maleic acid.According to reports, described copolymer has the ability that forms chelate with stannous ion, and described ability is enough strong, to prevent sub-stannum oxidation or to be precipitated out from solution.
Except in conjunction with or the sub-stannum of chelating, preferred polymer mineral surface active agent also has strong affinity to enamel surfaces, and will be in described enamel surfaces deposited polymer layer or coating, and produce desired surface protection and regulating effect.The suitable example of this base polymer is polyelectrolyte, such as the phosphorylation polymer of condensation; Polyphosphonate; the monomer that comprises phosphate radical or phosphonate radical or polymer and other monomer such as ethylenically unsaturated monomers and aminoacid or with the copolymer of other polymer, described other polymer is as protein, polypeptide, polysaccharide, poly-(acrylate), poly-(acrylamide), poly-(methacrylate), poly-(ethyl propylene acid esters), poly-(hydroxyalkyl methacrylate), poly-(vinyl alcohol), poly-(maleic anhydride), poly-(maleate), poly-(amide), poly-(vinylamine), PEG, poly-(propylene glycol), poly-(vinyl acetate) and poly-(vinyl chloride), the polymer of polycarboxylate and carboxyl substituted, and their mixture.Suitable polymer mineral surface active agent comprises the United States Patent (USP) 5,292,501,5,213,789,5,093,170,5,009,882 and 4,939 of all authorizing the people such as Degenhardt, the alkoxide polymer of the carboxyl substituted described in 284; Authorize the derivative polymer of diphosphate described in the people's such as Benedict United States Patent (USP) 5,011,913; And synthetic anionic polymer, for example comprise, such as authorizing the polyacrylate described in the people's such as Gaffar United States Patent (USP) 4,627,977 and the copolymer (Gantrez) of maleic anhydride or maleic acid and methyl vinyl ether.Preferred polymer is the polyacrylic acid of diphosphate modification.The activated polymer of tool has enough surface combination characteristics, so that the desorbing of thin film protein maintenance are attached in enamel surfaces.For dental surface, the polymer with end or side chain phosphate radical or phosphonate radical functional group is all preferred, yet have mineral, in conjunction with other polymer of activity, can confirm effectiveness according to absorption affinity.
Other example of the suitable polymer mineral surface active agent that comprises phosphonate radical comprises the US4 that authorizes the people such as Degenhardt, in 877,603 as the disclosed bisphosphonate salt of anti-calculus agent polymer; Authorize the people's such as Dursch US4,749,758 and GB1, the disclosed copolymer that comprises phosphonate groups being applicable in detergent and Cleasing compositions in 290,724 (all transferring Hoechst); And the US5 that authorizes the people such as Zakikhani, disclosed copolymer and the cotelomer that can be used for application in 980,776 and authorize the people's such as Davis US6,071,434, described application comprises and suppresses dirty and burn into coating, cement and ion exchange resin.Preferred polymer comprises GB1,290, the water solubility copolymer of disclosed vinyl phosphonate and acrylic acid and salt thereof in 724, wherein said copolymer comprises by weight approximately 10% to approximately 90% vinyl phosphonate and approximately 90% to approximately 10% acrylic acid by weight, more particularly, the vinyl phosphonate that wherein said copolymer has and acrylic acid weight rate are 70% vinyl phosphonic acid ratio 30% acrylic acid; 50% vinyl phosphonic acid ratio 50% acrylic acid; Or 30% vinyl phosphonic acid ratio 70% acrylic acid.Other preferred polymer comprises by Zakikhani and the disclosed water-soluble polymer of Davis, described polymer is by having the bisphosphonates of one or more unsaturated C=C keys or polyphosphonates monomer (as ethenylidene-1,1-di 2 ethylhexyl phosphonic acid and 2-(hydroxyl oxygen phosphino-) ethylidene-1,1-di 2 ethylhexyl phosphonic acid) make with at least another kind of copolymerization with other compound (as acrylate and methacrylate monomer) of unsaturated C=C key, as there are those of following structure:
1. acrylic acid and 2-(hydroxyl oxygen phosphino-) ethylidene-1 with following structure, the cotelomer of 1-di 2 ethylhexyl phosphonic acid:
2. there is the acrylic acid of following structure and the copolymer of vinyl di 2 ethylhexyl phosphonic acid:
Suitable polymer comprises bisphosphonates/acrylate polymer, and it take trade name ITC1087 (mean molecule quantity as 3000 to 60,000) and Polymer1154 (mean molecule quantity is 6000 to 55,000) by Rhodia provides.
Preferred mineral surface active agent can coexist with other component of preparation such as fluorion is stable, and is not hydrolyzed in high water content preparation, therefore can provide simple single phase dentifrice or collutory preparation.If mineral surface active agent does not have these stability characteristic (quality)s, a kind of selection is the biphase preparation of preparation mineral surface active agent and incompatible component physical separation.
Preferred polymer mineral surface active agent is polyphosphate.Although there are some cyclic polyphosphoric acid salt derivatives, it has been generally acknowledged that Quadrafos is comprised of two or more phosphate molecules of mainly arranging with linear configuration.Especially effectively average chain length is the polyphosphate of approximately four or more phosphate groups, so that the surface adsorption at valid density place can produce enough non-binding phosphate radicals functional group, this has strengthened surperficial anion form surface charge and water-wet behavior.Pyrophosphate and tripolyphosphate are discussed respectively in additional anti-calculus agent.Except other, long-chain polyphosphate also comprises four Quadrafos and hexametaphosphate.The Quadrafos larger than four Quadrafos occurs with amorphous glass material conventionally.The example of suitable polyphosphate is straight chain " glassy " polyphosphate with following formula:
XO(XPO 3) nX
Wherein X is sodium, potassium or ammonium, and the meansigma methods of n is approximately 6 to approximately 125.The polyphosphate of preferably being produced by FMC Corporation, it is commercially called as Sodaphos (n ≈ 6), Hexaphos (n ≈ 13) and Glass H (n ≈ 21).Most preferred polyphosphate is Glass H.These Quadrafos may be used singly or in combin.
Known average chain length is at ambient temperature greater than approximately 4 polyphosphate and will reacts with the fluorion in oral cavity composition, and except changing the pH of described compositions, also generates MFP radical ion.The effect that this reaction has damaged described oral cavity composition with and the ability of stablizing fluorion and polyphosphate is provided to oral surfaces.Also known polyphosphate can experience hydrolysis.Therefore, with this type of polyphosphate preparation, can present some difficulties.A kind of stable polyphosphate is to reduce total water content of described Dentrifice composition with precaution of hydrolysis and/or with the interactive method of incompatible composition.Authorize White, in the people's such as Jr. United States Patent (USP) 5,939,052, further described polyphosphate.Phosphate source is also described in greater detail in the Encyclopedia of Chemical Technology of Kirk-Othmer, and the 4th edition, in the 18th volume (Wiley-Interscience Publishers, 1996).
For the compositions forming for the condensation polyphosphate by thering are average 21 phosphate radical repetitives, the ideal ratio of having found phosphate radical anion total mole number and stannous ion total mole number is: the mol ratio of phosphate radical anion and stannous ion is approximately 0.2: 1 to approximately 5: 1, preferably approximately 0.5: 1 to approximately 3: 1, more preferably from about 0.6: 1 to approximately 2: 1, and most preferably from about 0.7: 1 to approximately 1: 1.
Except polyphosphate or as the substituting of polyphosphate, other polyphosphoric acid compound also can be used as mineral surface active agent/chelating agen, in particular to polyphosphoric acid inositol compound, such as phytic acid, inositol five (dihydric phosphate); Inositol four (dihydric phosphate), inositol three (dihydric phosphate), and their alkali metal salt, alkali salt or ammonium salt.Preferably phytic acid and its alkali metal salt, alkali salt or ammonium salt herein, phytic acid is also called as inositol 1,2,3,4,5,6-six (dihydrogen phosphoric acid ester) or phytic acid.Herein, term " phytic acid " comprises phytic acid and its salt and other polyphosphoric acid inositol compound.
Also spendable other non-polymeric mineral surface active agent is the chelating material that dental calculus object is recommended to form and remove after it forms for postponing dental calculus in this area.The chemistry route that suppresses dental calculus relates generally to chelating calcium ion and/or crystal growth inhibited, and it prevents from forming dental calculus and/or decomposing ripe dental calculus by removing calcium.These chelating agents are discussed in anti-calculus agent part below in more detail.
The aequum of mineral surface active agent in conjunction with sub-stannum, make to there is enough antimicrobial acivities, reduce teeth stains and preparation convergence and can reduce the effective dose of dental calculus.The effective dose of mineral surface active agent is generally approximately 0.05% to approximately 35% by the weighing scale of described total oral cavity composition, and preferably approximately 1% to approximately 30%, more preferably from about 5% to approximately 25%, and most preferably from about 6% to approximately 20%.
Except effectively, in conjunction with stannous ion, find, some mineral surface active agent/chelating agen also can be used as the solubilizing agent of the water-msoluble ingredients of described compositions.For example, find, Glass H polyphosphate can make insoluble tin salt and sub-tin-oxide and hydroxide dissolve.
polyvalent cation source
Compositions of the present invention preferably comprises the polyvalent cation source that is different from sub-stannum, comprises that inorganic ions is such as zinc (Zn + 2), copper (Cu + 2), aluminum (Al + 3), ferrum (Fe + 2, Fe + 3), strontium (Sr + 2), calcium (Ca + 2), barium (Ba + 2), magnesium (Mg + 2) and manganese (Mn + 2).This type of polyvalent cation and the competition of sub-stannum are incorporated in compositions to stablize the mineral surface active agent/chelating agen of sub-stannum by combination or chelating.Find, although chelation can be stablized sub-stannum effectively, this type of chemically stable stannous ion has very limited bioavailability, thereby has the therapeutic efficiency of minimizing.By there is the cation of competing with sub-stannum in same system, avoided the overstabilization of chelating agen to sub-stannum, cause while exchanging with competing cations and can obtain sub-stannum.Therefore, comprise the second polyvalent cation and can use chelating agen such as low-molecular-weight diphosphate, pyrophosphate and tripolyphosphate, described chelating agen has the sub-stannum of chelating but is tending towards reducing the ability of sub-stannum therapeutic efficiency.
The content in polyvalent cation source is enough to provide preferably 1: 1 or larger polyvalent cation and the mol ratio of sub-stannum conventionally.This guarantees that other polyvalent cation has enough concentration to compete mineral surface active agent with sub-stannum.The content of other polyvalent cation also depends on less important Consideration certainly, such as aesthetic property and the stability of described compositions, and can be lower than preferred 1: 1 ratio.Preferred polyvalent cation is for by salt such as nitrate, chloride, fluoride, phosphate, pyrophosphate, polyphosphate, sulfate, carbonate, citrate, lactate and oxalates or the inorganic cation that provided by oxide or hydroxide.Polyvalent cation source can be water miscible, partly soluble or insoluble.
In a preferred embodiment, described compositions comprise stannous fluoride as sub-Xi Yuan, as the zinc salt of zinc ion source with as the polyphosphate of mineral surface active agent/chelating agen.Described compositions can be formulated into single-phase product or biphase product, and wherein stannous fluoride and zinc salt are in the first compositions, and polyphosphate mineral surface active agent is in the second compositions.In another embodiment of two-phase compositions, the copolymer (Gantrez) that described the second compositions comprises maleic anhydride or maleic acid and methyl vinyl ether is as mineral surface active agent.In these embodiments, the preferred molar ratio of zinc ion and stannous ion is in the scope of approximately 0.5: 1 to approximately 5: 1.
In another embodiment, can be single-phase or biphase described compositions comprise calcium salt as calcium ion source, as the stannous fluoride in sub-Xi Yuan and fluorine source and as polyphosphate, maleic anhydride or the maleic acid of mineral surface active agent and the copolymer of methyl vinyl ether or their mixture.Two-phase compositions comprises stannous fluoride in the first compositions, and comprises calcium chloride and mineral surface active agent in the second compositions.
oral area acceptable carrier material
When preparation compositions of the present invention, wish one or more carrier materials or excipient to join in described compositions.This type of material is well known in the art, and is easy to be selected according to the desired physics of compositions to be prepared, aesthetics and Performance Characteristics by those skilled in the art.The content of these carriers is generally approximately 50% to approximately 99% by the weighing scale of described oral cavity composition, and preferably approximately 70% to approximately 98%, and more preferably from about 90% to approximately 95%.The example of examples of such optional carrier is described in paragraph below.
total water content
The water using when the commercial suitable oral cavity composition of preparation should be preferably low ion concentration and not contain organic impurities.In oral cavity composition, water content counts 0% at most approximately 95% by the weight of compositions described herein, and preferably approximately 5% to approximately 50%.This water content can be present in single-phase oral cavity composition, or can be the total water content of gained of biphase oral cavity composition.If it is approximately 4 or more polyphosphate that described oral cavity composition comprises average chain length, comprises the compositions of described polyphosphate or will comprise lower water content, total water content of general maximum approximately 20%.Total water content is preferably approximately 2% to approximately 20% by the weighing scale of described oral cavity composition, and more preferably from about 4% to approximately 15%, and most preferably from about 5% to approximately 12%.The water yield comprises the free water adding and the water of introducing with other material such as sorbitol, silicon dioxide, surfactant solution and/or colored solutions.
buffer agent
Compositions of the present invention can comprise buffer agent.As used herein, buffer agent refers to can be for being adjusted to approximately 3.0 reagent to approximately 10 scopes by described compositions pH value.In the oral cavity composition that comprises sub-stannum, conventionally have mutually approximately 3.0 to approximately 7.0, preferably approximately 3.25 to approximately 6.0, and 3.5 to approximately 5.5 serosity pH more preferably from about.What comprise mineral surface active agent/chelating agen has approximately 4.0 to approximately 10 mutually conventionally, and preferably approximately 4.5 to approximately 8, and 5.0 to approximately 7.0 serosity pH more preferably from about.The oral cavity composition that comprises Ya Xi and mineral surface active agent/chelating agen in single-phase has approximately 4 to approximately 7 conventionally, and preferably approximately 4.5 to approximately 6.5, and 5 to approximately 6 pH more preferably from about.
Suitable buffer agent comprises alkali metal hydroxide, carbonate, sesquicarbonate, borate, silicate, phosphate, imidazoles and their mixture.Concrete buffer agent comprises monosodium phosphate, tertiary sodium phosphate, sodium benzoate, benzoic acid, sodium hydroxide, potassium hydroxide, alkali carbonate, sodium carbonate, imidazoles, pyrophosphate, citric acid and sodium citrate.Preferred buffer be by pH regulator to target zone and can not coordinate those of stannous ion.Preferred buffer agent comprises acetic acid, sodium acetate, citric acid, sodium citrate, benzoic acid and sodium benzoate.The consumption of buffer agent counts approximately 0.1% to approximately 30% by the weight of compositions of the present invention, is preferably approximately 1% to approximately 10%, and more preferably approximately 1.5% to approximately 3%.
fluoride sources
Oral cavity composition of the present invention will optionally comprise the soluble fluoride source that bioavailable and effective fluorion can be provided.Soluble fluoride ion source comprises sodium fluoride, stannous fluoride, indium, amine fluoride and sodium monofluorophosphate.Stannous fluoride is preferred soluble fluoride source.This composition can be used as sub-Xi Yuan and fluorine source.The people's such as Widder that the people's such as Norris that announce July 26 nineteen sixty United States Patent (USP) 2,946,725 and on July 18th, 1972 announce United States Patent (USP) 3,678,154 discloses this type of fluorine source and other material.
The present composition can comprise soluble fluoride ion source, and described fluoride sources can provide about 50ppm to about 3500ppm, and preferred about 500ppm is to the free fluorine ion of about 3000ppm.In order to send the fluorion of desired amount, the content of fluoride sources in total oral cavity composition is approximately 0.1% to approximately 5% by the described general composition weight meter that is delivered to oral cavity, preferably approximately 0.2% to approximately 1%, and more preferably from about 0.3% to approximately 0.6%.
anti-calculus agent
The known material that forms relevant mineral deposit to dental calculus that can effectively reduce also can be used as mineral surface active agent/chelating agen or sub-stannum stabilizing agent in this article.Chelating agen can coordinate with the calcium being present in bacteria cell wall, and can be by calcium is removed to destroy dental plaque from the calcium bridge that contributes to these biomass are remained intact.Yet, do not wish to use the chelating agen that calcium was had to high-affinity, because this can cause tooth demineraliting, this deviates from mutually with object of the present invention and intention.The common calcium binding constant of suitable chelating agen is approximately 10 1to 10 5, so that the cleaning action that forms the dental plaque of minimizing and the improvement of calculus to be provided.Chelating agen also has the ability coordinating with metal ion, therefore can be used for stablizing sub-stannum.
Because thering is active this type of the available chelating agen of anti-dental calculus, comprise that pyrophosphate, tripolyphosphate and diphosphate are such as EHDP and AHP.The pyrophosphate that can be used as pyrophosphate ion source in the present composition comprises two alkali metal pyrophosphates, four alkali metal pyrophosphates and their mixture.Sodium Acid Pyrophosphate (Na 2h 2p 2o 7), tetrasodium pyrophosphate (Na 4p 2o 7) and tetrapotassium pyrophosphate (K 4p 2o 7) not hydration and hydrated form be preferred material.In compositions of the present invention, pyrophosphate can be with a kind of existence the in three kinds of modes: substantially dissolve, substantially do not dissolve or the mixture of dissolving and undissolved pyrophosphate.
The compositions that comprises the pyrophosphate substantially dissolving refers to that wherein at least one pyrophosphate ion source has enough amounts so that the compositions at least about 1.0% free pyrophosphate ion to be provided.The content of free pyrophosphate ions can be approximately 1% to approximately 15%, is approximately 1.5% to approximately 10% in one embodiment, is approximately 2% to approximately 6% in another embodiment.According to the difference of compositions pH value, free pyrophosphate ions can exist by various protonation states.
Comprising that the compositions of undissolved pyrophosphate refers to substantially comprises lower than approximately 20%, is preferably less than total pyrophosphate of approximately 10% and is dissolved in the compositions in compositions.In these compositionss, tetrasodium pyrophosphate is preferred pyrophosphate.In Dentrifice composition, tetrasodium pyrophosphate can be anhydrous form or decahydrate form or any other and is stable at the kind of solid form.Salt is its solid particulate form, and this form can be its crystallization and/or amorphous state.The particle diameter of salt is preferably enough little, can accept with in use soluble on attractive in appearance.The pyrophosphate amount of using during these compositionss in preparation is any amount that can effectively control dental calculus, and this amount is generally approximately 1.5% to approximately 15% by the weighing scale of described Dentrifice composition, preferred approximately 2% to approximately 10%, and most preferably from about 3% to approximately 8%.
Compositions also can comprise dissolving and mixture undissolved pyrophosphate.Can use above-mentioned any pyrophosphate of mentioning.
Pyrophosphate is described in greater detail in Kirk-Othmer Encyclopedia of Chemical Technology, the third edition, the 17th volume, Wiley-Interscience Publishers (1982).
Other example of chelating agen that can be used as anti-calculus agent comprises disclosed related compound in the British patent 490,384 of announcing on ethylenediaminetetraacetic acid, nitrilotriacetic acid and February 15 nineteen thirty-seven; The United States Patent (USP) of authorizing the people such as Widder of announcing on July 18th, 1972 is announced at August 16 in 3,678,154,1994 authorizes White, the United States Patent (USP) of authorizing the people such as Zerby 5 of United States Patent (USP) 5,338,537 Jr. and the announcement on the 19th of nineteen ninety-five JIUYUE, disclosed polyphosphonate in 451,401; Disclosed carbonyldiphosphonate salt in the United States Patent (USP) of authorizing Francis 3,737,533 of announcing on June 5th, 1973; Disclosed zinc-combination of polymers in the United States Patent (USP) of authorizing Gaffar 4,138,477 of announcing on February 6th, 1979, described combination by zinc compound and the anionic polymer that comprises carboxyl, sulfo group and/or phosphonate group react or reciprocal action forms; Disclosed tartaric acid in the United States Patent (USP) 5,622,689 that the United States Patent (USP) of all authorizing that the Decembers in 1998 15 days of Lukacovic announce is announced on April 22nd, 5,849,271 and 1997; Acid or salt form and their mixture of disclosed tartaric acid one succinic acid, tartaric acid disuccinic acid in the United States Patent (USP) of authorizing Smitherman 5,015,467 of announcing on May 14th, 1991; Disclosed acrylate copolymer or copolymer in the United States Patent (USP) of authorizing the people such as Benedict 4,661,341 of announcing in the United States Patent (USP) of authorizing the people such as Pyrz 4,847,070 that on July 11st, 1989 announces and on April 28th, 1987; Disclosed sodium alginate in the United States Patent (USP) of authorizing Pera 4,775,525 of announcing on October 4th, 1988; The GB741 that announce November 30 nineteen fifty-five, disclosed polyvinylpyrrolidone in the United States Patent (USP) of authorizing the people such as Pink 5,538,714 of announcing in the WO99/12517 that on March 18th, 315,1999 announces and on July 23rd, 1996; And the United States Patent (USP) of authorizing the people such as Venema 5 of announcing for 23rd JIUYUE in 1997, the copolymer of disclosed vinyl pyrrolidone and carboxylate in the Japanese publication 2000-0633250 that authorizes Lion Corporation announcing on February 29th, 670,138 and 2000.Other chelating agen that can be used as anti-calculus agent comprises gluconic acid, tartaric acid, citric acid and their pharmaceutically useful salt.Example comprises gluconic acid sodium salt or potassium gluconate and sodium citrate or potassium citrate; The combination of citric acid/alkali metal citrates; Three hydration zinc citrates; Disodium tartrate; Di-potassium tartrate; Sodium potassium tartrate tetrahydrate; Sodium bitartrate; Potassium hydrogen tartrate.Being applicable to this type of chelating dosage of the present invention is approximately 0.1% to approximately 2.5%, preferably approximately 0.5% to approximately 2.5%, and more preferably from about 1.0% to approximately 2.5%.
Also being applicable to other anti-calculus agent of the present invention is the United States Patent (USP) 4 of announcing on February 6th, 1979,138, the United States Patent (USP) of authorizing the people such as Gaffar 4 that on January 15th, 477 and 1980 announces, 183, disclosed polymer poly-carboxylate in 914, and comprise the copolymer of maleic anhydride or maleic acid and another kind of polymerizable ethylene linkage formula unsaturated monomer such as methyl vinyl ether (methoxy-ethylene), styrene, isobutene. or ethyl vinyl ether.These materials are well-known in the art, and they for example, with its free acid, part neutralization or the preferably form application of the water-soluble alkali of neutralization (potassium, and preferred sodium) salt or ammonium salt completely.Example is molecular weight (M.W.) is approximately 30,000 to approximately 1,000,000 the maleic anhydride of 1: 4 to 4: 1 and the copolymer of methyl vinyl ether.These copolymers for example obtain with trade name Gantrez AN139 (M.W.500,000), AN119 (M.W.250,000) and the S-97 pharmaceutical grade (M.W.70,000) of GAF Chemicals Corporation.
Other effective polymeric polycarboxylate comprises 1: 1 copolymer of maleic anhydride and ethyl acrylate, hydroxyethyl methylacrylate, NVP or ethylene, the latter can trade name Monsanto EMA No.1103 for example, MW10,000 and EMA Grade61 obtain, and 1: 1 copolymer of acrylic acid and methyl methacrylate or hydroxyethyl methylacrylate, acrylic acid methyl ester. or ethyl acrylate, IVE or NVP.
abrasive polishing material
Abrasive polishing material also can be comprised in oral cavity composition.Imagination can be the material of any not excessive wear dentine for the abrasive polishing material of the present composition.In addition, abrasive polishing material should be formulated in oral cavity composition, so that it does not damage the stability of sub-stannum or fluoride.For example, in biphase oral cavity composition, abrasive polishing material be preferably placed at the isolation of fluoride sources and stannous ion source mutually in.
Typical abrasive polishing material comprises: silicon dioxide, comprises gel and precipitation; Aluminium oxide; Phosphate, comprises orthophosphate, polymetaphosphate and pyrophosphate; And their mixture.Concrete example comprises the graininess condensation product of Bibasic Calcium Phosphate dihydrate, calcium pyrophosphate, tricalcium phosphate, poly-calcium metaphosphate, insoluble sodium hexametaphosphate, hydrated alumina, β-calcium pyrophosphate, calcium carbonate and resin abrasive material such as urea and formaldehyde, and other material, as the people's such as Cooley of December in 1962 announcement on the 25th United States Patent (USP) 3, disclosed in 070,510.Also can use the mixture of grinding agent.If it is approximately 4 or longer polyphosphate that oral cavity composition or Particle Phase comprise average chain length, the grinding agent of calcic and aluminium oxide are not preferred grinding agents.Most preferred grinding agent is silicon dioxide.
Preferred polytype silica dental abrasives, because they have unique beneficial effect of the polished performance that makes tooth clean especially but not excessive wear dentium nitor or dentine.The mean diameter of abrasive silica polishing material of the present invention and other grinding agent is conventionally at approximately 0.1 to approximately 30 micron, and preferably in the scope of approximately 5 to approximately 15 microns.Described grinding agent can be precipitated silica or silica gel, as authorized the people's such as Pader United States Patent (USP) 3,538,230 on March 2nd, 1970 and be published in the United States Patent (USP) 3 of authorizing DiGiulio on January 21st, 1975 being published in, silica xerogel described in 862,307.W.R.Grace & Company preferably, the silica xerogel of selling with trade name " Syloid " of Davison Chemical Division.Preferred precipitated silica material also, those as sold by J.M.Huber Corporation with trade name " Zeodent ", the especially silicon dioxide of called after " Zeodent119 ".The types of silica dental abrasives can be used in toothpaste of the present invention is described in greater detail in the United States Patent (USP) of authorizing Wason 4,340,583 of announcing July 29 nineteen eighty-two.Other suitable silica abrasive is described in United States Patent (USP) 5,589,160,5,603,920,5,651,958,5,658,553,5,716,601 and the White of Rice, in the people's such as Jr. United States Patent (USP) 6,740,311.Abrasive levels in oral cavity composition described herein is generally approximately 6% to approximately 70% by weight of the composition.Oral cavity composition preferably comprises by the grinding agent of the weighing scale of described oral cavity composition approximately 10% to approximately 50%.
peroxide source
The present invention also comprises peroxide source in described compositions.Described peroxide source choosing is the group of following composition freely: hydrogen peroxide, calper calcium peroxide, urea peroxide and their mixture.Preferred peroxide source is calper calcium peroxide.For stability is maximized, described peroxide source is not preferably arranged in mutually same with stannous ion source.Following amount represents the amount of peroxide raw material, although peroxide source also can comprise the composition outside peroxide raw material.The present composition can comprise by the weighing scale of described oral cavity composition approximately 0.01% to approximately 10%, and preferably approximately 0.1% to approximately 5%, more preferably from about 0.2% to approximately 3%, and 0.3% to approximately 0.8% peroxide source most preferably from about.
alkali metal hydrogencarbonate
The present invention also can comprise alkali metal hydrogencarbonate.Alkali metal hydrogencarbonate is water miscible.Unless stabilized, it is easy to release of carbon dioxide in Aquo System.The sodium bicarbonate that is also called as yeast powder is preferred alkali metal hydrogencarbonate.Described alkali metal hydrogencarbonate also can be used as buffer agent.Due to the pH of alkali metal hydrogencarbonate buffering, described bicarbonate be preferably placed at stannous ion source isolation mutually in.The present composition can comprise by the weighing scale of described oral cavity composition approximately 0.5% to approximately 50%, and preferably approximately 0.5% to approximately 30%, more preferably from about 2% to approximately 20%, and 5% to approximately 18% alkali metal hydrogencarbonate most preferably from about.
additional carrier
The present composition can be toothpaste, dentifrice, local by buccal cavity gel, collutory, artificial tooth product, mouth spraying agent, medicine caked sugar, buccal or gum formats, and conventionally comprises some thickening materials or binding agent so that desired denseness to be provided.The amount of thickening material and type will depend on product form.Preferred thickening agent is the water soluble salt of carboxy vinyl polymer, chondrus ocellatus Holmes polysaccharide, hydroxyethyl-cellulose and cellulose ether, such as sodium carboxymethyl cellulose and sodium hydroxyethyl cellulose.Also can use natural gum as karaya, xanthan gum, Radix Acaciae senegalis and Tragacanth.The silicon dioxide of colloidal magnesium aluminum silicate or segmentation can be used as part thickening agent further to improve texture.The consumption of thickening agent counts approximately 0.1% to approximately 15% by the weight of described oral cavity composition.
The another kind of optional components of desired compositions is wetting agent herein.Wetting agent can be used for preventing that oral cavity composition is because being exposed to hardening in air, and some wetting agent also can be given the sweet taste of dentifrice composition with expectation.The wetting agent being applicable in the present invention comprises glycerol, sorbitol, Polyethylene Glycol, propylene glycol, xylitol and other edible polyhydric alcohol.The content of described wetting agent is generally approximately 0% to 70% by the weighing scale of described oral cavity composition, and preferred approximately 15% to 55%.
Compositions of the present invention also can comprise surfactant, and it is conventionally also referred to as foaming agent.Suitable surfactant has the material of appropriate stability and foam for those within the scope of whole wide pH value.Surfactant can be anion, non-ionic, both sexes, zwitterionic, cationic or their mixture.The water soluble salt that can be used for the sulfonation monoglyceride of the fatty acid that anion surfactant of the present invention comprises the water soluble salt (as alkyl sodium sulfate) of the alkylsurfuric acid that contains 8 to 20 carbon atoms in alkyl and contain 8 to 20 carbon atoms.The example of this analog anion surfactants is sodium lauryl sulfate and coco group monoglyceride sulfonates.Other suitable anion surfactant is that sarcosinate is as sodium lauroyl sarcosine, taurate, lauryl sulfoacetate sodium, lauroyl sodium isethionate, laureth carboxylic acid sodium and dodecylbenzene sodium sulfonate.Also can use the mixture of anion surfactant.Many suitable anion surfactants are disclosed in to be authorized in the people's such as Agricola United States Patent (USP) 3,959,458 on May 25th, 1976.The non-ionic surface active agent can be used in the present composition can be broadly defined as the compound being generated with itself can be organic hydrophobic compound condensation of aliphatic series or alkyl aromatic by alkylidene oxide group (itself is hydrophilic).The example of suitable non-ionic surface active agent comprises poloxamer (selling with trade name Pluronic), polyoxyethylene, polyoxyethylene sorbitan ester (selling with trade name Tweens), Polyoxyl40 castor oil hydrogenated, alcohol ethoxylate, the condensation substance of alkyl phenol and poly(ethylene oxide), condensation product derived from the product of oxirane and propylene oxide and ethylenediamine, the ethylene oxide condensate of fatty alcohol, long chain tertiary amine oxide, long chain tertiary phosphine oxide, long-chain dialkyl sulphoxide, and the mixture of these materials.Described non-ionic surface active agent poloxamer188 is a kind of most preferred surfactant, because found that poloxamer contributes to reduce the convergence of sub-stannum.Can be used for amphoteric surfactant of the present invention and can be widely described the derivant into aliphatic secondary amine and tertiary amine, wherein aliphatic group can be straight or branched, and one of them aliphatic substituent group comprises approximately 8 to approximately 18 carbon atoms, and one comprises water-soluble anionic group, for example carboxylate radical, sulfonate radical, sulfate radical, phosphate radical or phosphonate radical.Other suitable amphoteric surfactantes are betanins, in particular to cocoamidopropyl.Also can use the mixture of amphoteric surfactant.In suitable nonionic and amphoteric surfactant, have in many United States Patent (USP)s 4,051,234 that are disclosed in the people such as Gieske that JIUYUE in 1977 announces on the 27th.Compositions of the present invention comprises one or more surfactants conventionally, and the content of each is approximately 0.25% to approximately 12% by weight of the composition, and preferably approximately 0.5% to approximately 8%, and most preferably from about 1% to approximately 6%.
Titanium dioxide also can join in compositions of the present invention.Titanium dioxide is that the white powder of opacity can be provided to compositions.The content of titanium dioxide is generally approximately 0.25% to approximately 5% by weight of the composition.
Coloring agent also can join in compositions of the present invention.Coloring agent can be the form of aqueous solution, is preferably the aqueous solution containing 1% coloring agent.The content of colored solutions is generally approximately 0.01% to approximately 5% by weight of the composition.
Also flavor system can be joined in described compositions.Suitable flavor components comprises wintergreen oil, Fructus Piperis peppermint oil, Oleum Menthae Rotundifoliae, clove bud oil, menthol, anethole, methyl salicylate, eucalyptol, Cortex Cinnamomi, acetic acid 1-menthyl ester, Salvia japonica Thunb., acetaminol, parsley oil, frambinone, α-ionone, marjoram, Fructus Citri Limoniae, orange, 1-ethoxy-2-hydroxy-4-propenyl benzene, Cortex cinnamomi japonici (Ramulus Cinnamomi), vanillin, ethyl vanillin, heliotropine, 4-cis-heptenal, diacetyl, 4-tert-Butylphenylacetic acid methyl ester, and their mixture.Coolant can be also a part for flavor system.In the present composition, preferred coolant is to alkylamino formyl reagent in the Meng, such as N-ethyl-to alkane-3-carboxylic acid amides in the Meng (commercial being called " WS-3 ") and their mixture.The consumption of flavor system in described compositions is generally approximately 0.001% to approximately 5% by weight of the composition.
Sweeting agent can be joined in compositions.These comprise glucide, glucose, sucrose, lactose, xylitol, maltose, fructose, aspartame, sodium cyclamate, D-trp, dihydrochalcone, acesulfame and their mixture.Also multiple coloring agent can be incorporated in the present invention.Sweeting agent and the coloring agent consumption in toothpaste is generally approximately 0.005% to approximately 5% by weight of the composition.
Except sub-stannum, the present invention also comprises other reagent so that antimicrobial beneficial effect to be provided.The content of these reagent does not hinder the reciprocal action between sub-stannum and mineral surface active agent.Being included in this type of antimicrobial is water-insoluble non-cationic antimicrobial, such as halogenated diphenyl ethers, oxybenzene compound (comprising phenol and homologue thereof), an alkyl and many alkyl and aromatic halophenols, resorcinol and derivant thereof, bisphenol compound and halo salicylamide, benzoin ester and halo carbanilide.Water soluble antimicrobials also comprises quaternary ammonium salt and two-bis-guanidinesalts etc.Triclosan monophosphate is additional water soluble antimicrobials.Quaternary ammonium reagent comprise one or two substituent carbon chain lengths (being generally alkyl) on quaternary nitrogen wherein for approximately 8 to approximately 20, be generally approximately 10 to 18 carbon atoms, remain substituent group (being generally alkyl or benzyl) simultaneously and there is lower carbon number 1 to approximately 7 carbon atom according to appointment, be generally those of methyl or ethyl.Typical quaternary ammonium antibacterial embodiment has Dodecyl trimethyl ammonium chloride, TPC, domiphen bromide, chlorination N-myristyl-4-ethylpyridine, dodecyl dimethyl (2-benzene oxygen ethyl) ammonium bromide, benzyl dimethyl stearyl chlorination ammonium, cetylpyridinium chloride, quaternised 5-amino-1, two (2-the ethylhexyl)-5-methyl hexahydropyrimidines of 3-, alkyl benzyl dimethyl ammonium chloride, benzethonium chloride and methyl benzethonium chloride.Other compound is two [4-(R-the is amino)-1-pyridine alkane that are disclosed in the United States Patent (USP) of authorizing Bailey 4,206,215 of announcing on June 3rd, 1980.Also can comprise other antimicrobial, such as Diglycocol copper, cupric glycinate, zinc citrate and zinc lactate.Enzyme usefully, comprises endo-glycosidase, papain, glucanase, glucosan allosteric hydrolytic enzyme (mutanase) and their mixture in addition.This type of reagent is disclosed in to be authorized the people's such as Norris United States Patent (USP) 2,946,725 July 26 nineteen sixty and authorizes in the people's such as Gieske United States Patent (USP) 4,051,234.Concrete antimicrobial comprises that chlorhexidine, triclosan, triclosan monophosphate and flavor oil are such as thymol.Other reagent of triclosan and this type is disclosed in authorizes Parran, the people's such as Jr. United States Patent (USP) 5,015,466 and authorizing in the people's such as Nabi United States Patent (USP) 4,894,220.If exist biphasely, water-insoluble biocides, water-soluble reagent and enzyme can be present in the first or second oral cavity composition.The content of these reagent counts approximately 0.01% to approximately 1.5% by the weight of described oral cavity composition.
Dentrifice composition can be paste, gel or their any configuration or combination.If expect biphase dentifrice, the first and second Dentrifice compositions will be located physically separately in dentifrice dispensers.Generally preferably the first Dentrifice composition is paste, and the second Dentrifice composition is gel.Described allotter can be pipe, pump or any other container that is applicable to dispensing toothpaste.The dual compartment package that is applicable to this object is described in the United States Patent (USP) 4,528,180 of all authorizing Shaeffer, United States Patent (USP) 4,687,663 and 4,849,213.Described allotter will be sent every kind of Dentrifice composition of approximate equivalent by opening.Described compositions can be mixed in minute timing.Alternatively, described oral preparation can be sent by the cover box that comprises two independent allotters, and described allotter is for send two kinds of Dentrifice compositions that use simultaneously.
effect is measured
The overall performance of compositions of the present invention can describe in detail according to the ratio of effect mark/mottle mark, wherein adopt external dental plaque glycolysis and regenerating model (i-PGRM) to measure effect, and adopt external thin film tea stain model (i-PTSM) to measure mottle.The effect mark that compositions of the present invention provides and the ratio of mottle mark are at least 1.2, and this represents actual improvement, has wherein kept sufficient therapeutic efficiency, realizes the minimizing of tooth discoloration simultaneously.The constringent improvement of preparation is defined as the xerostomia of definition in preparation mouthfeel parameter such as controlled consumption person test and oral cavity cleaning exponent increase more than 50%.Suppress the effect of dental calculus on gum by adopting the plaque growth of modification and the activity that prevents dental plaque calcification of mineralising detection assay to limit.
antimicrobial acivity
For different clinical effects, for example dental caries is compared with gingivitis, provides the required stannous ion concentration of therapeutical effect and the bioavailability can be different.Yet, determine that minimum antimicrobial acivity content is important, because lower than this content, the therapeutic activity of sub-stannum may be impaired.Occur therein to keep effect to be even more important in the compositions of sub-stannum combination, because sub-stannum is in conjunction with the loss that is easy to cause antimicrobial acivity., define the minimum effect being provided by stannous ion source according to the effect that causes dental plaque bacterial biof iotalm metabolic inhibition herein, described dental plaque bacterial biof iotalm is the reason that produces numerous worthless disease in mouth.Therefore, according to adopting the significantly significantly reduction of the metabolism of dental plaque on the spot of measuring at external dental plaque glycolysis and the regenerating model (i-PGRM) of our laboratory research and development to define effect.Confirm, i-PGRM can produce the active required stannous fluoride bioavailability of clinical antimicrobial, gingivitis and antiplaque to the oral cavity composition that comprises stannous fluoride fabulous dependency is provided.For the U.S.5 such as authorizing the people such as Majeti, the dentifrice formulation that comprises sub-stannum described in 004,597, or for the commercially available dentifrice Crest Gum Care that comprises stannous fluoride, can directly relatively comprise the effect of the compositions of sub-stannum to gingivitis.
I-PGRM is a technology, and wherein dental plaque produces from human saliva, and by the agent treated that is intended to form various different antimicrobial acivities.The object of this technology is to provide simple and fast method to come deterministic compound whether plaque microbiological to be had to direct effect for generation of the metabolic pathway of toxin, and described toxin can adversely affect gums health.Specifically, described model is directed to organic acid and produces, and comprises lactic acid, acetic acid, propanoic acid and butanoic acid.The method adopts and to be grown in the dental plaque on polished glass rod, and described Glass rod soaked overnight in saliva is soaked 6 hours in soybean broth and sucrose, then in saliva soaked overnight.Then, the water that is 3: 1 with ratio and dentifrice slurry are processed the dental plaque piece being grown on Glass rod 1 minute.Then, described speckle is placed 6 hours in soybean broth/sucrose solution, and when within 6 hours, finishing, measured the pH of described culture fluid.Therefore, to test formulation and tester, the pH before all measure cultivating and cultivate after pH.Conventionally, this test is repeatedly repeated farthest to reduce experimental variance, and calculate average pH by retest.Due to the strong reactivity with sugar decomposition organism, therefore at i-PGRM, detect in analytic process, the compositions of the sub-stannum of bioavailable that comprises high-load produces significant inhibitory action to the formation of dental plaque acid.This is sub-stannum stability and the bioavailability of more various preparations easily.
Stannous fluoride and/or other tin salt are present in oral cavity composition as herein described so that desired i-PGRM score to be provided with effective dose.Such as the U.S.5 that authorizes the people such as Majeti, described in 004,597, with respect to not comprising the preparation (negative control) of sub-stannum and with respect to the preparation that comprises sub-stannum (positive control), measuring desired i-PGRM score.Most preferred i-PGRM score is significantly different from placebo, and is similar in theory by being proved and can effectively reduces those that the conventional stannous fluoride compositions of dental plaque and gingivitis provides.Research confirms, for containing at least about 60%, and preferably at least about 70%, and more preferably at least about the compositions of 80% the effective dentifrice that comprises sub-stannum as shown in below example II comparative example, measurable effective gingivitis effect.
According to following formula, calculate i-PGRM score:
The pH of the culture medium obtaining after average pH reference and processing and sucrose competition.Without a large amount of acid of tester dental plaque Sample producing of sub-stannum, so their pH is lower than the pH (the stable stannous fluoride dentifrice as shown in example II comparative example) of the dental plaque sample of processing with positive control.The preparation effectiveness being made by the combination of stannous ion source and mineral surface active agent is suitable with the tester that comprises sub-stannum in theory, and therefore theoretic i-PGRM score should approach 100%.
reduce tooth discoloration
Tooth discoloration is inadvisable side effect common while using stannous fluoride compositions.By the sub-stannum of being combined with mineral surface active agent, more effectively sending Ya Xi makes the stannous fluoride dentifrice through improving as herein described can reduce forming of teeth stains.Conventionally the dental surface variable color being caused by Ya Xi can be by adopting Lobene or the Meckel index of mottle index described in document to measure under clinical setting.Also researched and developed external tooth discoloration model, it provides and the closely-related qualitative assessment to stannous fluoride preparation tooth discoloration potential of clinic observation.Therefore, adopt these methods before clinical examination, to preparation, to measure.
Described external thin film tea stain model (i-PTSM) is a technology, and wherein external dental plaque biomass were excited saliva from the human body gathering and are grown on Glass rod within three day time.The water that is 3: 1 with ratio and dentifrice supernatant are processed dental plaque biomass, and wherein grinding agent and insoluble solid are removed by centrifugal, measure the potential tooth discoloration degree of various reagent.The object of this technology is to provide simply and fast method to come deterministic compound whether dental plaque mottle measurer to be had to direct effect.The method adopts and is grown in the dental plaque on polished glass rod from the human saliva gathering, and described Glass rod is each to be processed 5 minutes, then with tea, processes 10 minutes.Before dental plaque biomass stripping Glass rod, processing scheme is repeated at least three times, filter and measure the absorptance at 380nm place.Conventionally this test is repeatedly repeated, farthest to reduce experimental variance, and calculate average absorbance by retest.
Find, by stannous fluoride is mixed with a kind of mineral surface active agent discussed above or its mixture, can reduce the mottle conventionally being produced by effective stannous fluoride.By compositions of the present invention, can obtain the beneficial effect that reduces the tooth discoloration being caused by Ya Xi, and can significantly not damage the effect of sub-stannum, fluoride and mineral surface active agent.The tooth discoloration degree that the tooth discoloration degree being produced by oral cavity composition of the present invention significantly produces lower than the typical dentifrice by comprising sub-stannum.As used herein, term " minimizing " refers to the remarkable minimizing in statistical significance.Therefore, reduce sub-stannum mottle and refer to respect to the positive control that comprises sub-stannum, in mottle amount statistical significance, significantly reduced.Do not reduce sub-stannum effect and refer to respect to the positive control that comprises sub-stannum, the effect of sub-stannum does not have the remarkable reduction in statistical significance.Alternatively, can measure mottle with respect to typical oral cavity composition, described oral cavity composition does not comprise stannous fluoride or another kind has been notified painted antimicrobial.Therefore, measure described compositions and there is relatively considerably less mottle extremely without mottle.
According to following formula, tooth discoloration detects analytic process and calculates i-PTSM score thus:
Average absorbance value refers to the stripping dental plaque colourimetric number obtaining after dentifrice treatment and tea competition.Sub-stannum tester used is generally highly colored stannous fluoride preparation, as shown in below example II comparative example.Sub-stannum tester sample causes that a large amount of tea absorbs, so colorimetric absorptance increases.Therefore, i-PTSM must be divided into measuring of colourity vis-a-vis.Score is lower, and degree of staining is just lower.The combination of stannous ion source and mineral surface active agent provides painted reduction, and will have ideally and be less than approximately 75%, is preferably less than 60%, is more preferably less than 50%, is most preferably less than 25% i-PTSM score.
the ratio of i-PGRM score and i-PTSM score
The key improvement descriptor of sub-stannum compositions provided herein be sub-stannum effect with respect to the ratio of painted potential, these are that consumer is concerned about emphatically.The effect that can measure oral cavity composition of the present invention by the ratio of i-PGRM score and i-PTSM score.
According to following formula, calculate the ratio of i-PGRM score and i-PTSM score:
Ratio=i-PGRM score/i-PTSM score
According to the present invention, because sub-stannum preparation effect obtains significant improvement with respect to tooth discoloration side effect, the ratio that therefore adopts these methods to obtain should be at least about 1.2.Described ratio is preferably higher than approximately 1.3, more preferably higher than approximately 1.5, and most preferably higher than approximately 2.0.If almost colourless speckle generates, described ratio approach infinity, this is preferred.
the combination of sub-stannum
As mentioned above, by stannous ion being combined on the spot with mineral surface active agent or coordinating effectively stable (reduced side effects effectively, simultaneously) that can realize sub-stannum.In comprising the blend compositions of stannous fluoride, by obtaining the potential determination of fluorion, the sign of sub-stannum combination will be easy to observe.For example, the combination of Ya Xi and polyphosphate mineral surface active agent part causes fluorine to exchange from stannous fluoride, and as Fluoride release in solution.Because fluorine is the strongest part in system after mineral surface active agent bonding agent, therefore technology is evaluated the related assays of sub-stannum combination thus.Therefore, fluorine release is the illustration that Ya Xi is combined with MSA under these conditions.
Adopt the method to determine coordinating of sub-stannum and zinc ion and polyphosphate mineral surface active agent.Because stannous ion can be coordinated by multi-phosphate anion, therefore adopt the fluorine release detection analytic process of ion selectivity fluoride electrode to can be used for monitoring stannous ion to the release of fluorine and cooperation.In stannous fluoride solution, add Glass H polyphosphate, owing to forming Ya Xi-polyphosphate complex and discharging fluorion subsequently from stannous fluoride complex, therefore can produce free fluorion.Because zinc ion has the affinity higher than stannous ion to multi-phosphate anion, therefore zinc salt is joined in the mixture of stannous fluoride and polyphosphate and will be conducive to form zinc-polyphosphate complex, and discharge the stannous ion coordinating with free fluorine subsequently.Therefore, add zinc ion will reduce the content of free fluorine ion.
Preparation comprises separately the solution of stannous fluoride and comprises stannous fluoride and the solution of zinc salt.To increasing progressively in these solution, add Glass H polyphosphate solution, and via fluoride ion selective electrode monitoring fluorion.The following two kinds of solution of preparation.
Solution 1:SnF 20.454%
Solution 2:SnF 20.454%+ZnCl 21.25% (zinc ion of 6000ppm)
To each in these solution, titration 0.1M Glass H polyphosphate (22%w/v), and measure fluorion.Using the concentration of free fluorine as the function of added titration dosage, data are mapped.This external metal-ligand coordinates result of study to be presented in following table.It will be 1100ppm free fluorine that the theory of 0.454% stannous fluoride is released fluorine amount.Because most of fluorine in the solution that comprises stannous fluoride coordinate with stannous ion, therefore there is considerably less free fluorine.Along with adding of polyphosphate, free fluorine ion significantly increases, and approaches the theoretical value of 1100ppm.This is to form Ya Xi-polyphosphate complex because stannous fluoride coordinates with multi-phosphate anion, discharges fluorion from stannous fluoride complex simultaneously.Zinc ion is joined in stannous fluoride solution, reduced the content of free fluorine ion, increased multi-phosphate content simultaneously.This shows, zinc ion, contributes to stannous ion to discharge from Ya Xi-polyphosphate complex in conjunction with multi-phosphate anion by competition.
Solution composition Free fluorine ion (ppm)
SnF 2(0.454％) 29
The SnF mixing with polyphosphate (6.2%) 2(0.454％) 669
SnF 2(0.454％)+ZnCl 2(1.2%)+polyphosphate (6.2%) 355
reduce convergence
Convergence is the additional side effect of many compositionss that comprise sub-stannum, and it significantly improves in the present composition that comprises mineral surface active agent and Ya Xi and the combination of the second polyvalent cation.The convergence of measuring preparation with oral cavity group form, wherein experimenter evaluates oral conditions before brushing teeth by test formulation He after brushing teeth.In these researchs, the research of time dependence can consist of the impact of consumer's subjective response dentifrice.In a scheme, the self-oral cavity health that panelist strengthens by use is carried out cleaning teeth, starts series conditioning, comprise and brush teeth twice, each three minutes, with dental floss tooth-cleaning and development to guarantee that dental plaque removes completely.Then, to experimenter, distribute their test products and instruct them to brush teeth every day twice routinely.For these tests, experimenter reported to clinical portion morning before carrying out any oral cavity health or pickuping food or beverage, then require panelist to fill in individual mouthfeel evaluation questionnaire, comprise about the problem of cleaning of teeth sense, tooth smooth feeling and oral cavity cleaning sense and the assessment of mouth-moistening degree.Then, panelist brushes teeth one minute with the dental products of appointment.Now, a.p with supper before (at dusk), experimenter fills in individual mouthfeel questionnaire again.The result of these tests shows, obtains significantly improvement aspect the preparation convergence of the preparation of the present invention that comprises the combination of tin salt and mineral surface active agent such as Glass H polyphosphate after brushing teeth.Compare with the sub-stannum preparation of the routine that does not contain mineral surface active agent, convergence reduces.The acceptability of preparation of the present invention is suitable with tartar inhibition dentifrice with conventional sodium fluoride (NaF) respectively.
reduce and inhibition dental calculus
Another necessary aspect that anti-dental calculus beneficial effect is stannous fluoride preparation of the present invention is provided.Can be by mineral surfaces activity measurement and plaque growth and mineralize detect analytic process should be used for predict that anti-dental calculus is active.Compositions of the present invention comprises mineral surface active agent, such as the polyphosphate in conjunction with stannous ion.Preferred compositions comprises mineral surface active agent phosphate polymer dental surface to remarkable affinity, and it consists of hydroxyapatite.Preferred mineral surface active agent comprises phosphate polymer, in analyzing, determines as detected in controlled calcium ore deposit, and it obtains significant reduction aspect calcium phosphate mineralising.Find, with respect to pyrophosphate and some other conventional cleaning of teeth composition, polyphosphate (the straight chain polyphosphate that specifically, average chain length is greater than approximately 4) can produce oral surfaces better active and direct.Active and direct increase is converted into the remarkable improvement that teeth stains and gum upper tooth prevention of stones and the non-abrasiveness of teeth stains are removed.Not bound by theory, it is believed that polyphosphate prevents the generation of dental calculus on gum by destroying in essence the process of mineralizing, described in the process of mineralizing be on dentium nitor, to form hard calcium phosphate mineral deposition.By in conjunction with dental surface, polyphosphate has destroyed mineral accumulation process, this be because their structure not fully the meeting of laminating in growing up become the mineral lattice of dental calculus.
therapeutic Method
The invention still further relates to the application of the invention compositions treatment gingivitis and dental plaque, reduce the method for tooth discoloration simultaneously, described compositions comprises stannous ion source, be different from the polyvalent metal ion source of sub-stannum and mineral surfaces activity/chelating agen such as average chain length is approximately 4 or more straight chain polyphosphate.Fluoride sources preferably is contained in compositions, especially in stannous ion source, does not comprise in the situation of stannous fluoride or the sub-stannum of fluorophosphoric acid.The method of oral care composition is also provided, and described compositions has dental caries, gingivitis, antiplaque, anti-calculus, antiplaque, antiallergic, attractive in appearance, breath freshening, mouthfeel and clean beneficial effect.When described in Reusability during compositions, the beneficial effect of these compositionss can increase in time.Specifically, Therapeutic Method will comprise to be surveyed as i-PGRM, reduces gingivitis and dental plaque, simultaneously as i-PTSM survey, the tooth discoloration that minimizing is caused by the oral cavity composition that comprises sub-stannum.The ratio of i-PGRM score and i-PTSM coloring models score is higher than approximately 1.2.
The invention still further relates to and reduce the method that occurs the method for dental calculus on enamel and desired oral cavity aesthetic feeling beneficial effect is provided, comprise and reduce convergence and oral surfaces conditioning effect.When described in Reusability during compositions, the beneficial effect of these compositionss can increase in time.
Therapeutic Method comprises prepares oral cavity composition and to experimenter's applying said compositions, said composition comprises stannous ion source, is different from polyvalent cation source and the mineral surface active agent (MSA) of sub-stannum.To experimenter, use and may be defined as by brushing teeth with dentifrice or cleaning to make oral care composition contact experimenter dental surface by dentifrice slurry.Also can be by buccal cavity gel for part, collutory, artificial tooth product, mouth spraying agent, buccal, medicine caked sugar or chewing gum contact dental surface be used.Experimenter can be any human or animal who needs treatment or prevention oral disease, and described oral disease comprises dental plaque, gingivitis, tartar, mottle and allergy.Specifically, " animal " is intended to comprise house pet or other domestic animal or the animal encaging.
For example, processing method can comprise that someone scrubs the tooth of Canis familiaris L. with a kind of Dentrifice composition.Another example comprises with oral cavity composition the sufficiently long time of mouth rinsing of cat to see beneficial effect.Can prepare the pet care product that comprises this oral cavity composition, as chaw and toy.The compositions that comprises Ya Xi, the second cation and mineral surface active agent is incorporated in more soft but robust and durable material, such as rawhide, by rope natural or that synthetic fibers are made and the polymer product made by nylon, polyester or thermoplastic polyurethane.When animal chew, tongue are licked or bite the said goods, contained active component is released in the saliva substrate in the oral cavity of animal, and this is equivalent to effectively scrub or rinsing.
Embodiment
The embodiment in the scope of the invention has further been illustrated in the following example and description.These given embodiment are only used to illustrate, and should not be considered to limitation of the present invention, because do not departing under the condition of the spirit and scope of the invention, can carry out many changes to it.
example I
Example I shows biphase Dentrifice composition, described compositions is mixed with stannous fluoride and/or other tin salt in the first Dentrifice composition, and in the second Dentrifice composition, be mixed with mineral surface active agent such as sodium polyphosphate (the Glass H being provided by FMC Corporation, n=21, condensed phosphate polymer) or the copolymer (Gantrez) of maleic anhydride or maleic acid and methyl vinyl ether.The second polyvalent cation source is incorporated in arbitrary compositions.The conventional method that these compositionss are suitable for being selected by formulator makes.
the first Dentrifice composition
Composition 1a 2a 3a 4a 5a
Stannous fluoride 1.062 1.062 1.062 1.062 -
Stannous chloride 1.500 - - - 1.500
Zinc lactate - - ? 5.000 -
Zinc carbonate - - 5.000 - -
Sodium fluoride -- - - - 0.486
27.9% sodium lauryl sulfate solution - - 2.500 2.500 7.500
Gluconic acid sodium salt 3.290 1.300 2.940 1.840 4.135
50% sodium hydroxide solution 0.600 0.600 0.600 0.280 0.900
Saccharin sodium 0.400 0.400 0.400 0.300 0.400
Flavoring agent 1.500 1.300 1.300 1.200 1.100
1% blue No. 1 dye solution of FD&C 0.300 0.300 0.300 0.100 0.500
Polyethylene Glycol - - - - 6.000
Poloxamer188 15.500 15.500 17.500 16.500 7.000
70% sorbitol solution 23.000 23.000 - - 36.879
Glycerol 31.008 31.008 22.000 22.000 20.000
Xanthan gum - - 0.850 - 1.100
Hydroxyethyl-cellulose - - - - 0.500
Polyoxyethylene - - 0.200 - -
Water 21.840 25.530 45.348 49.218 12.000
the second Dentrifice composition
Composition 1b 2b 3b 4b 5b
Glass H Quadrafos 25.800 20.800 26.000 - 18.000
Gantrez - 5.000 - 5.000 -
Zinc lactate - - - - 5.000
Calcium chloride 1.712 1.712 - - -
Carboxymethyl cellulose 0.500 0.500 0.200 0.200 0.300
Water 2.210 2.210 - 32.150 1.400
Flavoring agent 1.500 1.500 1.100 1.100 1.100
Glycerol 28.178 28.178 45.550 20.550 34.850
Polyethylene Glycol 1.500 1.500 - - 6.000
Propylene glycol 8.000 8.000 - - -
Polyoxyethylene 0.200 0.200 - - -
27.9% sodium lauryl sulfate solution 10.000 10.000 8.000 10.000 6.000
Silicon dioxide 15.000 15.000 18.150 30.000 26.000
Polyoxyl40 castor oil hydrogenated 2.500 2.500 - - -
Benzoic acid 0.600 0.600 - - 0.300
Sodium benzoate 0.600 0.600 - - 0.300
Saccharin sodium 0.400 0.400 0.400 0.400 0.350
Titanium dioxide 1.000 1.000 0.500 0.500 0.400
Xanthan gum 0.300 0.300 0.100 0.100 -
example II
Example II shows single phase dentifrice compositions, and described compositions is mixed with tin salt as stannous ion source, polyvalent cation source and as Glass H sodium polyphosphate or the Gantrez of mineral surface active agent.Described compositions can be used conventional method to make.
Dimension disclosed herein and value are not intended to be understood to strictly be limited to described exact value.On the contrary, except as otherwise noted, each such dimension refers to quoted numerical value and around the scope being equal in the function of this numerical value.For example, the dimension that is disclosed as " 40mm " is intended to represent " about 40mm ".
The All Files of quoting in detailed Description Of The Invention is all incorporated herein by reference in relevant portion.For quoting of any file, should not be interpreted as admitting that it is relevant prior art of the present invention.In this written document, any implication of term or while defining contradiction in any implication of term or definition and the file that is incorporated to way of reference, should obey implication or the definition of in this written document, giving this term.
Although illustrated and described specific embodiment of the invention scheme, having it will be apparent to one skilled in the art that and can make a plurality of other changes and modification in the situation that not departing from essence of the present invention and scope.Therefore all such change and modification that, claims are intended to be included in the scope of the present invention.

Claims (7)

1. an oral care composition, described compositions has the antimicrobial acivity that effectively reduces dental plaque and gingivitis, and described compositions comprises:
A. stannous ion source, wherein said stannous ion source is selected from stannous fluoride, two hydrated stannous chlorides, stannous acetate, the sub-stannum of gluconic acid, stannous oxalate, stannous sulfate, the sub-stannum of lactic acid, stannous tartrate and their mixture;
B. the polyvalent cation source that is different from sub-stannum, described polyvalent cation source is selected from zinc (Zn + 2), copper (Cu + 2), ferrum (Fe + 2, Fe + 3), strontium (Sr + 2), barium (Ba + 2), magnesium (Mg + 2), manganese (Mn + 2) and their mixture;
C. mineral surface active agent, wherein said mineral surface active agent comprises the copolymer of maleic anhydride or maleic acid and methyl vinyl ether; With
D. the abrasive polishing material that contains silicon dioxide,
Described compositions provides sub-stannum stability and the therapeutic efficiency of enhancing.
2. oral care composition as claimed in claim 1, described compositions comprises approximately 0.05% to approximately 35% condensed phosphoric acid fluidized polymer.
3. oral care composition as claimed in claim 2, wherein said phosphorylation polymer is the straight chain polyphosphate with approximately 2 to approximately 125 average chain length.
4. oral care composition as claimed in claim 1, described compositions also comprises the freely material of the group of following composition of choosing: fluoride sources, antibacterial, surfactant, thickening material, wetting agent, buffer agent, titanium dioxide, flavor system, sweeting agent, coloring agent and their mixture.
5. oral care composition as claimed in claim 4, wherein said fluoride sources choosing is the group of following composition freely: sodium fluoride, stannous fluoride, indium, amine fluoride, sodium monofluorophosphate and their mixture.
6. oral care composition as claimed in claim 4, wherein said thickening material choosing is the group of following composition freely: carboxy vinyl polymer, chondrus ocellatus Holmes polysaccharide, hydroxyethyl-cellulose, sodium carboxymethyl cellulose, sodium hydroxyethyl cellulose, karaya, xanthan gum, Radix Acaciae senegalis, Tragacanth, Magnesiumaluminumsilicate, silicon dioxide and their mixture.
7. an oral care composition, described compositions comprises:
(a) the first compositions that comprises stannous ion source, wherein said stannous ion source is selected from stannous fluoride, two hydrated stannous chlorides, stannous acetate, the sub-stannum of gluconic acid, stannous oxalate, stannous sulfate, the sub-stannum of lactic acid, stannous tartrate and their mixture;
(b) the second compositions that comprises mineral surface active agent, wherein said mineral surface active agent comprises the copolymer of maleic anhydride or maleic acid and methyl vinyl ether; With
(c) be present in the polyvalent cation source that is different from sub-stannum in described the first and second compositionss any one or two kinds of, described polyvalent cation source is selected from zinc (Zn + 2), copper (Cu + 2), ferrum (Fe + 2, Fe + 3), strontium (Sr + 2), barium (Ba + 2), magnesium (Mg + 2), manganese (Mn + 2) and their mixture,
Wherein said mineral surface active agent stannous ion described in chelating when described the first compositions contacts in oral cavity with the second compositions, and wherein said oral care composition comprises the abrasive polishing material that contains silicon dioxide.
CN201410208416.2A 2006-10-02 2006-10-02 Oral nursing stannous composition Pending CN104069013A (en)

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108348409A (en) * 2015-11-13 2018-07-31 宝洁公司 Dentifrice composition with improved fluoride stability
CN108601851A (en) * 2015-10-21 2018-09-28 密执安州立大学董事会 Dental caries and microcavity are detected and treated with nanoparticle
CN111989083A (en) * 2018-03-29 2020-11-24 宝洁公司 Oral care composition for promoting gum health
CN112118823A (en) * 2018-05-14 2020-12-22 宝洁公司 Oral care compositions comprising fluoride ions
CN114025735A (en) * 2019-06-28 2022-02-08 宝洁公司 Oral care compositions comprising tin ions
US11839671B2 (en) 2019-06-28 2023-12-12 The Procter & Gamble Company Oral care compositions comprising tin ions
US11839672B2 (en) 2019-06-28 2023-12-12 The Procter & Gamble Company Dentifrice compositions comprising tin ions
US12023388B2 (en) 2021-04-12 2024-07-02 The Regents Of The University Of Michigan Detection and treatment of caries and microcavities with nanoparticles

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US4335102A (en) * 1979-09-20 1982-06-15 Lion Corporation Oral composition for caries prophylaxis

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Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108601851A (en) * 2015-10-21 2018-09-28 密执安州立大学董事会 Dental caries and microcavity are detected and treated with nanoparticle
CN108348409A (en) * 2015-11-13 2018-07-31 宝洁公司 Dentifrice composition with improved fluoride stability
CN111989083A (en) * 2018-03-29 2020-11-24 宝洁公司 Oral care composition for promoting gum health
CN111989083B (en) * 2018-03-29 2024-02-13 宝洁公司 Oral care composition for promoting gingival health
CN112118823A (en) * 2018-05-14 2020-12-22 宝洁公司 Oral care compositions comprising fluoride ions
CN112118823B (en) * 2018-05-14 2023-07-28 宝洁公司 Oral care compositions comprising fluoride ions
CN114025735A (en) * 2019-06-28 2022-02-08 宝洁公司 Oral care compositions comprising tin ions
US11839671B2 (en) 2019-06-28 2023-12-12 The Procter & Gamble Company Oral care compositions comprising tin ions
US11839672B2 (en) 2019-06-28 2023-12-12 The Procter & Gamble Company Dentifrice compositions comprising tin ions
US12023388B2 (en) 2021-04-12 2024-07-02 The Regents Of The University Of Michigan Detection and treatment of caries and microcavities with nanoparticles

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Application publication date: 20141001