WO2009109533A1

WO2009109533A1 - Bleach catalysts and their use as teeth whitening agents

Info

Publication number: WO2009109533A1
Application number: PCT/EP2009/052407
Authority: WO
Inventors: Hauke Rohwer; Olof Wallquist
Original assignee: Basf Se
Priority date: 2008-03-07
Filing date: 2009-02-27
Publication date: 2009-09-11

Abstract

The instant invention pertains to a process and to an oral composition which when applied onto the surface of teeth acts to whiten teeth. More particularly, it relates to a process and an oral composition with an improved teeth whitening effect comprising a safe and effective amount of peroxy compounds, terpyridine transition metal complexes as catalysts and in addition, optionally further adjuvants.

Description

Bleach Catalysts and their Use as Teeth Whitening Agents

The instant invention pertains to a process and to an oral composition which when applied onto the surface of teeth acts to whiten teeth. More particularly, it relates to a process and an oral composition with an improved teeth whitening effect comprising a safe and effective amount of peroxy compounds, terpyridine transition metal complexes as catalysts and in addition, optionally further adjuvants, such as, for example, particulate abrasive cleaning agents. A further aspect of the invention is the use of terpyridine transition metal complexes as catalysts for oral tooth whitening compositions.

A tooth is comprised of an inner dentin layer and an outer hard enamel layer that is the protective layer of the tooth. The enamel layer of a tooth is naturally an opaque white or slightly off-white color. It is this enamel layer that can become stained or discolored. The enamel layer of a tooth is composed of hydroxyapatite mineral crystals that create a somewhat porous surface. It is believed that this porous nature of the enamel layer is what allows staining agents and discoloring substances to permeate the enamel and discolor the tooth. Pre-eruptive disorders as well as internal bleeding could also cause intrinsic discoloration.

Many substances that a person confronts or comes in contact with on a daily basis can "stain" or reduce the "whiteness" of one's teeth. In particular, the foods, tobacco products and fluids such as tea and coffee that one consumes tend to stain one's teeth. These products or substances tend to accumulate on the enamel layer of the tooth and form a pellicle film over the teeth. These staining and discoloring substances can then permeate the enamel layer. This problem occurs gradually over many years, but imparts a noticeable discoloration of the enamel of one's teeth.

The use of peroxy compounds in oral care compositions has already been proposed in the prior art. Many peroxy compounds have been suggested for whitening/bleaching human teeth, and representative examples of such peroxy compounds are hydrogen peroxide, urea peroxide, organic peracids, such as perphthalic acid, diperoxycarboxylic acids, 1 ,12- dodecanedioic peroxy acid, peroxy acetic acid and systems comprising a peroxy compound and a peroxy acid precursor which generate peroxy acetic acid in situ, such as sodium perborate and tetraacetylethylene diamine (TAED). The use of peroxy acetic acid is suggested in particular in e.g. EP-A0545,594, which also sets out the various prior proposals, made in the art for several peroxy compounds as bleaching/whitening agent for human teeth. However, these compositions are considered to have a slow bleaching effect, and the peracids have limited application due to their poor instability, low pH environment causing erosion of enamel and inability to penetrate enamel due to bulk size of the molecule.

In order to obtain an acceptable bleach result, high peroxy concentrations have to be applied, which causes sensitization and is not safe for the oral mucosa.

WO 00/59461 , therefore, suggests adding as a further compound to tooth bleach pastes iron complexes as catalysts to accelerate the bleaching effect. However, the suggested iron complexes provide only a slight acceleration of the beaching effect.

WO 97/02805 discloses, for example Mn-gluconate as bleach catalyst in tooth paste. The disadvantage of Mn-gluconates is, however, the high concentration which is necessary to produce a noticeable whitening effect.

It has now been found that the combined use of selected transition metal terpyridine complexes and peroxy compounds leads to a significant improvement of the bleach result in terms of whitening effect and reduced bleach time.

One aspect of the invention is an oral care composition for the whitening of teeth comprising a) a peroxy compound; b) a compound of formula (1 )

[L_nMe_mXp]Υ_q (1 ),

wherein Me is manganese, titanium, iron, cobalt, nickel or copper, X is a coordinating or bridging radical, n and m are each independently of the other an integer having a value of from 1 to 8, p is an integer having a value of from 0 to 32, z is the charge of the metal complex, Y is a counter-ion, q = z/(charge Y), and L is a ligand of formula (2)

wherein

Ri, R2, R3, R₄, Rs, Re, R₇, Rs, R9, R10 and Rn are each independently of the others hydrogen; unsubstituted or substituted Ci-Ci₈alkyl or aryl; cyano; halogen; nitro; - COOR₁₂ or -SO3R₁₂ wherein R₁₂ is in each case hydrogen, a cation or unsubstituted or substituted Ci-Ci₈alkyl or aryl; -SRi₃, -SO2R13 or -OR13 wherein R₁₃ is in each case hydrogen or unsubstituted or substituted Ci-Ci₈alkyl or aryl; -NR₁₄R₁₅; -(C_rC₆alkylene)-NR₁₄R₁₅; -N⁰R₁₄R₁₅Ri₆; -(C₁-C₆alkylene)-N^ΘR₁₄R₁₅R₁₆; -N(R₁₃HC₁- C₆alkylene)-NR₁₄R₁₅; -N[(CrC6alkylene)-NR₁₄R₁₅]₂; -N(R₁₃)-(C_rC₆alkylene)-

N⁰R₁₄R₁₅R₁₆, -N[(C₁-C₆alkylene)-N^ΘR₁₄R₁₅R₁₆]₂; -N(R₁₃)-N-R₁₄R₁₅ or -N(R₁₃)- N⁰R₁₄R₁₅R₁₆, wherein R₁₃ is as defined above and R₁₄, R₁₅ and R₁₆ are each independently of the other(s) hydrogen or unsubstituted or substituted CrC-isalkyl or aryl, or R₁₄ and R₁₅ together with the nitrogen atom bonding them form an unsubstituted or substituted 5-, 6- or 7-membered ring which may optionally contain further heteroatoms; or Ri, R2, R3, R₄, R5, R₆, R7, Re, R9, R10 and R₁₁ are each independently of the others a

CH, group __N' NH- — YJ N-CHXHX)H ■ — N. N-CH, ■ — N N.

CH,

_^CH₂CH₂OH _,,CH₂CH₂OH or — N N.

CH₂CH₂OH and optionally c) a further adjuvant.

The CrC₁₈alkyl radicals mentioned are generally, for example, straight-chain or branched alkyl radicals, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl or straight-chain or branched pentyl, hexyl, heptyl or octyl. Preference is given to CrC₁₂alkyl - A -

radicals, especially Ci-C₈alkyl radicals and preferably Ci-C₄alkyl radicals. The mentioned alkyl radicals can be unsubstituted or substituted e.g. by hydroxyl, CrC₄alkoxy, sulfo or by sulfato, especially by hydroxyl. The corresponding unsubstituted alkyl radicals are preferred. Very special preference is given to methyl and ethyl, especially methyl.

Examples of aryl radicals that generally come into consideration are phenyl or naphthyl unsubstituted or substituted by Ci-C₄alkyl, Ci-C₄alkoxy, halogen, cyano, nitro, carboxyl, sulfo, hydroxyl, amino, N-mono- or N,N-di-Ci-C₄alkylamino unsubstituted or substituted by hydroxy in the alkyl moiety, N-phenylamino, N-naphthylamino, where the amino groups may be quaternized, phenyl, phenoxy or by naphthoxy. Preferred substituents are Ci-C₄alkyl, Ci-C₄alkoxy, phenyl and hydroxy. Special preference is given to the corresponding phenyl radicals.

The Ci-C₆alkylene groups mentioned are generally, for example, straight-chain or branched alkylene radicals such as methylene, ethylene, n-propylene or n-butylene. The alkylene radicals mentioned can be unsubstituted or substituted, for example by hydroxyl or Ci-C₄alkoxy.

Halogen is generally preferably chlorine, bromine or fluorine, special preference being given to chlorine.

Examples of cations that generally come into consideration are alkali metal cations, such as lithium, potassium and especially sodium, alkaline earth metal cations, such as magnesium and calcium, and ammonium cations. The corresponding alkali metal cations, especially sodium, are preferred.

Suitable metal ions for Me are e.g. manganese in oxidation states N-V, titanium in oxidation states III and IV, iron in oxidation states I to IV, cobalt in oxidation states I to III, nickel in oxidation states I to III and copper in oxidation states I to III, with special preference being given to manganese, especially manganese in oxidation states Il to IV, preferably in oxidation state II. Also of interest are titanium IV, iron N-IV, cobalt N-III, nickel N-III and copper N-Nl, especially iron N-IV. For example, Me is manganese which is present in oxidation state II, III, IV or V; or Fe in oxidation state II, III or IV.

Preferably Me is manganese which is present in oxidation state II, III, IV or V.

For the radical X there come into consideration, for example, CH₃CN, H₂O, F^", Cl^", Br^", HOO^", O₂ ^2", O^2", Ri₇COO^", R₁7O^", LMeO^" or LMeOO^" wherein R₁₇ is hydrogen, -SO₃Ci-C₄alkyl, or unsubstituted or substituted Ci-Ci₈alkyl or aryl, and L and Me are as defined above. Ri₇ is especially preferably hydrogen, d-C₄alkyl; sulfophenyl or phenyl, especially hydrogen.

As counter-ion Y there come into consideration, for example, Ri₇COO^", CIO₄ ^", BF₄ ^", PF₆ ^", Ri₇SO₃ ^", Ri₇SO₄ ^", SO₄ ^2", NO₃ ^", F^", Cl^", Br^", I^", citrate, tartrate or oxalate wherein R_i7 is hydrogen or unsubstituted or substituted Ci-Ci₈alkyl or aryl. Ri₇ as Ci-Ci₈alkyl or aryl has the definitions and preferred meanings given hereinabove and hereinbelow. Ri₇ is especially preferably hydrogen, Ci-C₄alkyl; phenyl or sulfophenyl, especially hydrogen or 4-sulfophenyl. The charge of the counter-ion Y is accordingly preferably 1- or 2-, especially 1-. Y can also be a customary organic counter-ion, such as citrate, oxalate or tartrate.

For example, n is an integer having a value of from 1 to 4, preferably from 1 to 2.

For example, m is an integer having a value of 1 or 2, especially 1.

For example, p is an integer having a value of from O to 4, preferably from O to 2.

For example, z is an integer having a value of from 8- to 8+, preferably from O to 2+.

Ri₂ is preferably hydrogen, a cation, Ci-Ci₂alkyl, or phenyl unsubstituted or substituted as indicated above. Ri₂ is especially preferably hydrogen, an alkali metal cation, alkaline earth metal cation or ammonium cation, Ci-C₄alkyl or phenyl, more especially hydrogen or an alkali metal cation, alkaline earth metal cation or ammonium cation.

Ri₃ is preferably hydrogen, Ci-Ci₂alkyl, or phenyl unsubstituted or substituted as indicated above. R_i3 is especially preferably hydrogen, Ci-C₄alkyl or phenyl, more especially hydrogen or CrC₄alkyl, preferably hydrogen. Examples of the radical of the formula -ORi₃ that may be mentioned include hydroxyl and CrC₄alkoxy, such as methoxy and especially ethoxy.

When R₁₄ and Ri₅ together with the nitrogen atom bonding them form a 5-, 6- or 7-membered ring it is preferably an unsubstituted or d-C₄alkyl-substituted pyrrolidine, piperidine, piperazine, morpholine or azepane ring, where the amino groups can optionally be quaternized, preferably the nitrogen atoms which are not directly bonded to one of the three pyridine rings A, B or C being quaternized. The piperazine ring can be substituted by one or two unsubstituted CrC₄alkyl and/or substituted CrC₄alkyl e.g. at the nitrogen atom not bonded to the phenyl radical. In addition, R₁₄, R₁₅ and R₁₆ are preferably hydrogen, unsubstituted or hydroxyl-substituted CrC₁₂alkyl, or phenyl unsubstituted or substituted as indicated above. Special preference is given to hydrogen, unsubstituted or hydroxyl- substituted CrC₄alkyl or phenyl, especially hydrogen or unsubstituted or hydroxyl-substituted CrC₄alkyl, preferably hydrogen.

Preference is given to compounds wherein the ligand L is a compound of formula (2)

wherein

R'₃, R'₆ and R'g are each independently of the others phenyl unsubstituted or substituted by CrC₄alkyl, CrC₄alkoxy, halogen, phenyl or hydroxyl; cyano; nitro; -COOR₁₂ or -SO₃R₁₂, wherein R₁₂ is in each case hydrogen, a cation, CrC₄alkyl or phenyl; -SR₁₃, -SO₂R₁₃ Or -OR₁₃ wherein R₁₃ is in each case hydrogen, CrC₄alkyl or phenyl, -N(CH₃)-NH₂ Or -NH-NH₂; amino; N-mono- or N,N-di-CrC₄alkylamino unsubstituted or substituted by hydroxy in the alkyl moiety, wherein the nitrogen atoms, may be quaternized; N-mono- or N,N-di-CrC₄alkyl- N⁰R₁₄R₁₅R₁₆, unsubstituted or substituted by hydroxy in the alkyl moiety, wherein R₁₄, R₁₅ and R₁₆ are each independently of the others hydrogen, unsubstituted or hydroxyl-substituted CrC₁₂alkyl, or phenyl unsubstituted or substituted as indicated above, or R₁₄ and R₁₅ together with the nitrogen atom bonding them form a pyrrolidine, piperidine, morpholine or azepane ring unsubstituted or substituted by at least one CrC₄alkyl or by at least one unsubstituted CrC₄alkyl and/or substituted CrC₄alkyl wherein the nitrogen atom can be quaternized; N-mono- or N,N-di-Ci-C₄alkyl-NR₁₄R₁₅ unsubstituted or substituted by hydroxy in the alkyl moiety, wherein R₁₄ and Ri₅ can have the meanings indicated above; or a radical

- (CH₂)₀— N N

^ ' ^R18 wherein R₁₇ and Ri₈ are Ci-C₄alkyl or d-C₄alkyl substituted by OH; R₃' and R₉' can have additionally the meaning of hydrogen.

Especially important as radicals R₆ and R₆' are Ci-C₄alkoxy; hydroxy; hydrazine; amino; N-mono- or N,N-di-Ci-C₄alkylamino unsubstituted or substituted by hydroxy in the alkyl moiety, wherein the nitrogen atoms, especially the nitrogen atoms which are not bonded to one of the three pyridine rings A, B or C, may be quaternized; or a pyrrolidine, piperidine, piperazine, morpholine or azepane ring unsubstituted or substituted by at least one Ci-C₄alkyl, wherein the nitrogen atoms may be quaternized. A further especially important example of R₆ is the radical

wherein the ring and the two alkyl groups may additionally be substituted.

Very especially important as radicals R₆ and R₆' are Ci-C₄alkoxy; hydroxy; N-mono- or N,N-di-Ci-C₄alkylamino substituted by hydroxy in the alkyl moiety, wherein the nitrogen atoms, especially the nitrogen atoms which are not bonded to one of the three pyridine rings A, B or C, may be quaternized; or a pyrrolidine, piperidine, morpholine or azepane ring unsubstituted or substituted by at least one CrC₄alkyl, wherein the amino groups may be quaternized.

A further very especially important example of R₆' is the radical

wherein the ring and the two alkyl groups may additionally be substituted.

As examples of the radical R₆', particular mention may be made of — N N ^■ — N N-CH₂CH₂OH — N N-CH, ^■

_V1-1^CH₂CH₂OH _V1+^CH₂CH₂OH

— N N- ■ — NCH₂CH₂N(CH₃)₃ ; -NCH₂CH₂N(CH₃)₂

CH, — N N.

CH₂CH₂OH CH, CH,

-NHCH₂CH₂N(CH₃)_{3 ;} -NHCH₂CH₂N(CH₃)_{2 ;} -N[CH₂CH₂N(CH₃)₃]₂ -N[CH₂CH₂N(CH₃) 2J2

-N[CH₂CH₂CH₂N(CH₃)₂]₂ and -N[CH₂CH₂CH₂N(CH₃)₃]₂.

For R₆' hydroxyl is of particular interest.

The preferred meanings given above for R₆ and R₆' apply also to Ri, R₂, R3, R3', R₄, R5, R7, R₈, Rg, Rg', R10 and Rn, but these radicals may additionally be hydrogen.

Particular preference for R₃' and R₆' in formula (2) is given to hydrogen, N-mono- or N,N-di- Ci-C₄alkylamino unsubstituted or substituted by hydroxy in the alkyl moiety, or a group

\₊,CH₃

— N N ^■ — N N-CH₀CH₀OH ■ — N N-CH, ^■ — N N.,

XH,

— ₂CH₂N(CH₃)₂

-NHCH₂CH₂N(CH₃)_{3 ;} -NHCH₂CH₂N(CH₃)_{2 ;} -N[CH₂CH₂N(CH₃)₃]_{2 ;} -N[CH₂CH₂N(CH₃) 2J2

-N[CH₂CH₂CH₂N(CH₃)₂]₂ and -N[CH₂CH₂CH₂N(CH₃)₃]₂.

Preferred individual compounds are the following.

The compounds mentioned above are known and for example described in WO 02/88289 und WO 04/007657. They can be prepared according to the methods described therein.

Typically the peroxy compound is selected from the group consisting of hydrogen peroxide, peroxyacids and their salts, peroxydiphosphate, urea peroxide, metal peroxides, and the salts of perborate, persilicate, perphosphate, percarbonate and mixtures thereof.

The most suitable peroxygen compound for this invention is hydrogen peroxide.

The composition of the invention has particular application in toothpaste formulations, to form a new and improved composition within the purview of the invention comprising a peroxy compound bleach as defined above, the aforesaid transition metal complex catalysts having general formula (1 ) and particulate abrasive cleaning agents. The composition can also be formulated in an oral rinse form that can be used alone or as part of a oral care regimen to provide improved benefits.

In another embodiment, the composition of the present invention is part of a tooth cleaning gel. The transition metal complex catalyst will be present in the oral care composition according to the invention in amounts so as to provide the required level in the mouth. Generally, the transition metal complex catalyst level in the composition corresponds to a transition metal complex content of from 0.0005% to 0.5% by weight. The dosage of toothpaste in the mouth is, e.g. about 1-2 g, the transition metal complex content in the formulation is suitably 0.0025 to 0.5%, preferably 0.005 to 0.25% by weight. At higher product dosages, the transition metal complex content in the formulation is suitably 0.0005 to 0.1 %, preferably 0.001 to 0.05% by weight.

On a molar basis, the concentrations of the metal complex catalysts are typically 0.5-500μ Mol/I in the mouth, corresponding to approximately 1.5-1500μ Mol/kg toothpaste.

Compositions of the invention are effective over a wide pH-range of between 7 and 13, with optimal pH-range lying between 8 and 10.

Most preferred peroxy compound is hydrogen peroxide in the native form or in the complexed form such as hydrogen peroxide:polymer adducts, but it may also be a compound which is capable of yielding hydrogen peroxide in aqueous solution. Hydrogen peroxide sources are well known in the art. They include the alkali metal peroxides, organic peroxides such as urea peroxide, and inorganic persalts, such as the alkali metal perborates, percarbonates, perphosphates persilicates and persulphates. Mixtures of two or more such compounds may also be suitable.

Inorganic peroxyacid compounds are also suitable as peroxy compounds (component a)), such as for example potassium monopersulphate (MPS). If organic or inorganic peroxyacids are used as the peroxygen compound, the amount thereof will normally be within the range of about 2-10 % by weight, preferably from 4-8 % by weight.

All these peroxy compounds may be utilized alone or in conjunction with a peroxyacid bleach precursor and/or an organic bleach catalyst not containing a transition metal. Generally, the bleaching composition of the invention can be suitably formulated to contain from 0.001 to 15%, preferably from 0.01 to 5% by weight, of the peroxy bleaching agent. A useful class of peroxyacid bleach precursors is that of the cationic i.e. quaternary ammonium substituted peroxyacid precursors as disclosed in US-A-4,751 ,015 and USA- 4,397,757, in E P-A-0, 284, 292 and EP-A-331 ,229. Examples of peroxyacid bleach precursors of this class are: 2-(N,N,N-trimethyl ammonium) ethyl sodium-4-sulphophenyl carbonate chloride - (SPCC); N-octyl,N,N-dimethyl-N₁₀-carbophenoxy decyl ammonium chloride - (ODC) ;

3-(N,N,N-trimethyl ammonium) propyl sodium-4-sulphophenyl carboxylate; and N,N,N-trimethyl ammonium toluyloxy benzene sulphonate.

Any one of these peroxyacid bleach precursors can be used in the present invention, although some may be more preferred than others.

Of the above classes of bleach precursors, the preferred classes are the esters, including acyl phenol sulphonates and acyl alkyl phenol sulphonates; the acyl-amides; and the quaternary ammonium substituted peroxyacid precursors.

Examples of said preferred peroxyacid bleach precursors or activators are sodium-4- benzoyloxy benzene sulphonate (SNOBS); N,N,N'N'-tetraacetyl ethylene diamine (TAED); sodium-l-methyl-2-benzoyloxy benzene-4-sulphonate; sodium-4methyl-3-benzoloxy benzoate; 2-(N,N,N-trimethyl ammonium) ethyl sodium-4-sulphophenyl carbonate chloride (SPCC); trimethyl ammonium toluyloxy-benzene sulphonate; sodium nonanoyloxybenzene sulphonate (SNOBS); and sodium 3,5,5trimethyl hexanoyl-oxybenzene sulphonate (STHOBS).

The precursors may be used in an amount of up to 12 %, preferably from 1-10 % by weight, of the composition.

For example the further adjuvant is selected from the group consisting of water, pharmaceutically acceptable carriers, anionic, nonionic, amphoteric surfactants, particulate abrasive materials, humectants, binders, thickeners, flavors, preservatives, opacifying agents, coloring agents, pH-adjusting agents, sweetening agents, stabilizing compounds, anti-bacterial agents, anti-inflammatory agents, anti-caries agents, plaque buffers, vitamins, desensitizing agents, buffers, liposomes, anti-calculus agents and mixtures thereof. The oral compositions can be formulated in any suitable application form, such as gels, mouthwashes, toothpowders and toothpastes. An alternative product form may be an adhesive patch which fits over the tooth surface and keeps the bleaching agents in contact with the tooth surface for a short period of time, e.g. over-night. They may be formulated into a single formulation or they may be formulated for multi compartment containers into different formulations, e.g. one containing the peroxy compound and ingredients compatible therewith, and another containing the remaining ingredients. The oral composition can also be applied on to the surface of tooth enamel with an applicator ('paint-on product').

The oral care compositions of the present invention may furthermore comprise optional, conventional ingredients such as pharmaceutically acceptable carriers like starch, sucrose, water or water/alcohol systems etc.. Small amounts of surfactants may also be included, such as anionic, nonionic and amphoteric surfactants. When formulated into a dentifrice, such formulation may contain all the usual dentifrice ingredients.

Thus, they may comprise particulate abrasive materials such as silicas, aluminas, calcium carbonates, dicalciumphosphates, calcium pyrophosphates hydroxyapatites, trimetaphosphates, insoluble hexametaphosphates, agglomerated particulate abrasive materials and so on, usually in amounts between 5 and 60 % by weight.

Furthermore, the dentifrice formulations may comprise humectants such as glycerol, sorbitol, propyleneglycol, xylitol, lactitol and so on.

Binders and thickeners such as sodium carboxymethylcellulose, xanthan gum, gum arabic etc. may also be included, as well as synthetic polymers such as polyacrylates and carboxyvinyl polymers such as Carbopol^®

Flavours such as peppermint and spearmint oils may also be included, as well as preservatives, opacifying agents, colouring agents, pH-adjusting agents, sweetening agents and so on. Stabilising agents for the organic peroxy compounds such as dipicolinic acid or sodium stannate may also be usefully included.

Anti-bacterial agents may also be included such as Triclosan, chlorhexidine, copper-, zinc- and stannous salts such as zinc citrate, sodium zinc citrate and stannous pyrophosphate, sanguinarine extract, metronidazole. Further examples of anti-bacterial agents are quaternary ammonium compounds such as cetylpyridinium chloride; bis-guanides such as chlorhexidine digluconate, hexetidine, octenidine, alexidine; halogenated bisphenolic compounds such as 2,2' methylenebis-(4-chloro-6-bromophenol).

Polymeric compounds which can enhance the delivery of active ingredients such as antibacterial agents can also be included. Examples of such polymers are copolymers of polyvinylmethylether with maleic anhydride and other similar delivery enhancing polymers, e.g. those described in DE-A-3,942,643.

Furthermore anti-inflammatory agents such as ibuprofen, flurbiprofen, aspirin, indomethacin etc. may also be included.

Anti-caries agents such as sodium- and stannous fluoride, aminefluorides, monosodiumfluorophosphate, casein, plaque buffers such as urea, calcium lactate, calcium glycerophosphate, strontium polyacrylates may also be included, other optional ingredients include vitamins such as Vitamin C, and plant extracts. Desensitising agents such as potassium citrate, potassium chloride, potasium tartrate, potassium bicarbonate, potassium oxalate, potassium nitrate as well as strontium salts may also be included.

Buffers and salts to buffer the pH and ionic strength of the compositions may also be included. The pH of the compositions usually ranges from 5-10, preferably 6-9 and especially preferably 7-9.

Liposomes and other encapsulates may also be used to improve delivery or stability of active ingredients.

Furthermore, the oral compositions may comprise anti-calculus agents such as alkalimetal pyrophosphates, hypophosphite-containing polymers, organic phosphonates, alkalimetal tripolyphosphates, phosphocitrates etc.

In addition, the compositions may comprise functional biomolecules such as bacteriocins, antibodies, enzymes and so on. Other optional ingredients that may be included are e.g. effervescing systems such as sodium bicarbonate/citric acid systems, colour change systems, and so on.

When formulated as a mouthwash, the oral care composition usually comprises a water or water/alcohol solution, flavour, humectant, sweetener and colorant.

Another aspect of the invention is a method of whitening stained or discolored teeth in the oral cavity which comprises applying to the teeth an oral care composition as described above.

The method of whitening stained or discolored teeth in the oral cavity can also be carried out in two steps, which comprises applying to the teeth in a first step a) a compound of formula (1 ) according to claim 1 and in a second step b) a peroxy compound optionally with further adjuvants.

For example, the metal complex catalyst of the formula (1 ) can be applied in a tooth paste. The peroxy compound may afterwards be applied in a mouth wash.

Also an aspect of the invention is the use of a compound of formula (1 ) as described above together with a peroxy compound for the whitening of teeth.

All definitions and preferences given for the composition apply also for the other aspects of the invention.

The transition metal catalysts may be used in different teeth bleaching procedures:

• Stand alone bleach products containing catalyst and hydrogenperoxide / peroxygen source

• Hydrogenperoxide / peroxygen source and catalyst containing oral care products • Catalyst containing oral care product followed by a treatment with a hydrogenperoxide / peroxygen source containing product.

The invention is illustrated by the following examples. Following transition metal complexes are used:

1. Peroxide Bleaching of Morin Solution:

5μM catalyst solution is added at time t=0 to a solution of 160μM morin in 2OmM borate buffer pH 8.0 containing 200mmol/l hydrogen peroxide. The solution is located in a thermostatically controllable vessel, equipped with a magnetic stirrer, at 23°C. The extinction of the solution is measured at 410nm over a period of 10 min. The values for the reduction of discoloration after 2 minutes are indicated as percentages in Table 1.

Table 1 Morin Bleach

2. Peroxide Bleach of artificially stained Bovine Teeth

One bovine tooth is treated with 5.0ml of 2OmM borate buffer pH 8.0 and 20OmM hydrogen- peroxide. The catalyst concentrations are 12.5μM Compound 101 or 25μM Compound 103 . The bleach process is carried out in a glass beaker for 60 min. at ambient temperature. The bleach results are evaluated by measuring the difference of the Lightness ΔY (Lightness difference according to CIELAB formula) spectrophotometrically (7 readings per tooth). Each experiment consists of 4 independent bleach experiments using 4 different bovine teeth. The results are presented in Table 2. Δ L is the difference in lightness of the respective tooth before and after treatment.

Tab. 2 ΔY after Bleach Application

Both catalysts exhibit a very good bleach performance.

3. Bovine Teeth - Catalyst Soak followed by Hvdrogenperoxide Bleach The experiment is carried out in a way that the teeth are soaked in a solution of catalyst in borate buffer for 30 minutes; following this soaking period hydrogenperoxide (final concentration 20OmM) is added. The concentrations (after peroxide addition) are 12.5μM Compound 101 and 25μM Compound 103, which is the same concentration as in the experiments presented above. The results are given in Table 3.

Tab. 3 ΔY after Soak + Bleach Application

Both catalysts exhibit a very good bleach performance.

Claims

1. An oral care composition for the whitening of teeth comprising a) a peroxy compound; b) a compound of formula (1 )

[L_nMe_mXp]Υ_q (1 ).

wherein Me is manganese, titanium, iron, cobalt, nickel or copper,

X is a coordinating or bridging radical, n and m are each independently of the other an integer having a value of from 1 to 8, p is an integer having a value of from 0 to 32, z is the charge of the metal complex,

Y is a counter-ion, q = z/(charge Y), and

L is a ligand of formula (2)

wherein

Ri, R2, R3, R₄, Rs, Re, R7, Rs, R9, R10 and Rn are each independently of the others hydrogen; unsubstituted or substituted Ci-Ci₈alkyl or aryl; cyano; halogen; nitro; - COOR₁₂ or -SO3R₁₂ wherein R₁₂ is in each case hydrogen, a cation or unsubstituted or substituted Ci-Ci₈alkyl or aryl; -SRi₃, -SO2R13 or -OR13 wherein R₁₃ is in each case hydrogen or unsubstituted or substituted Ci-Ci₈alkyl or aryl; -NR₁₄R₁₅; -(CrC₆alkylene)-NRi4Ri5; -N⁰R₁₄R₁₅Ri₆; -(C₁-C₆alkylene)-N^ΘR₁₄R₁₅R₁₆; -N(R₁₃HC₁- C₆alkylene)-NR₁₄R₁₅; -N[(CrC6alkylene)-NR₁₄R₁₅]₂; -N(R₁₃)-(C_rC₆alkylene)-

N⁰R₁₄R₁₅R₁₆, -N[(C₁-C₆alkylene)-N^ΘR₁₄R₁₅R₁₆]₂; -N(R₁₃)-N-R₁₄R₁₅ or -N(R₁₃)- N⁰R₁₄R₁₅R₁₆, wherein R₁₃ is as defined above and R₁₄, R₁₅ and R₁₆ are each independ- ently of the other(s) hydrogen or unsubstituted or substituted Ci-Ci₈alkyl or aryl, or R₁₄ and R-_I5 together with the nitrogen atom bonding them form an unsubstituted or substituted 5-, 6- or 7-membered ring which may optionally contain further heteroatoms; or Ri, R₂, R3, R₄, R5, Re, R7, Re, R9, R10 and Rn are each independently of the others a group __{N NH}. __{N N}__CH2CH2o_H . ___N N-_CH_{3 ;} — N N^* _Ch| ³ ;

/ \ .CH₂CH₂OH / \ ₊,CH₂CH₂OH

-^N^^:CH₃ °^r -^N _W ^{N^}CH₂CH₂OH and optionally c) a further adjuvant.

2. An oral care composition according to claim 1 wherein Me is manganese which is present in oxidation state II, III, IV or V; or Fe in oxidation state II, III or IV.

3. An oral care composition according to claim 1 or 2 wherein Me is manganese which is present in oxidation state II, III, IV or V.

4. An oral care composition according to any preceding claim wherein X is CH₃CN, H₂O, F^", Cl^", Br^", HOO^", O₂ ^2", O^2", R₁7COO^", R₁₇O^", LMeO^" or LMeOO^" wherein R₁₇ is hydrogen, -SO₃Ci-C₄alkyl, or unsubstituted or substituted Ci-Ci₈alkyl or aryl, and L and Me are as defined in claim 1.

5. An oral care composition according to any preceding claim wherein Y is R₁₇COO^", CIO₄ ^", BF₄ ^", PF₆ ^", Ri₇SO₃ ^", Ri₇SO₄ ^", SO₄ ^2", NO₃ ^", F^", Cl^", Br^", I^", citrate, tartrate or oxalate wherein R₁₇ is hydrogen or unsubstituted or substituted CrC₁₈alkyl or aryl.

6. An oral care composition according to any preceding claim wherein m is an integer having a value of 1 or 2, especially 1.

7. An oral care composition according to any preceding claim wherein p is an integer having a value of from O to 4.

8. An oral care composition according to any preceding claim wherein z is an integer having a value of from 8- to 8+.

9. An oral care composition according to any preceding claim wherein the ligand L is a compound of formula

wherein

R'₃, R'₆ and R'₉ are each independently of the others phenyl unsubstituted or substituted by

CrC₄alkyl, CrC₄alkoxy, halogen, phenyl or hydroxyl; cyano; nitro; -COORi₂ or -SO₃Ri₂, wherein R₁₂ is in each case hydrogen, a cation, Ci-C₄alkyl or phenyl; -SRi₃, -SO₂Ri₃ or -ORi₃ wherein Ri₃ is in each case hydrogen, Ci-C₄alkyl or phenyl, -N(CH₃)-NH₂ Or -NH-NH₂; amino; N-mono- or N,N-di-Ci-C₄alkylamino unsubstituted or substituted by hydroxy in the alkyl moiety, wherein the nitrogen atoms, may be quaternized; N-mono- or N,N-di-CrC₄alkyl- N^ΘRi₄Ri₅Ri6, unsubstituted or substituted by hydroxy in the alkyl moiety, wherein Ri₄, Ri₅ and Ri₆ are each independently of the others hydrogen, unsubstituted or hydroxyl-substituted Ci-Ci₂alkyl, or phenyl unsubstituted or substituted as indicated above, or Ri₄ and Ri₅ together with the nitrogen atom bonding them form a pyrrolidine, piperidine, morpholine or azepane ring unsubstituted or substituted by at least one Ci-C₄alkyl or by at least one unsubstituted CrC₄alkyl and/or substituted CrC₄alkyl wherein the nitrogen atom can be quaternized; N-mono- or N,N-di-Ci-C₄alkyl-NRi₄Ri₅ unsubstituted or substituted by hydroxy in the alkyl moiety, wherein Ri₄ and Ri₅ can have the meanings indicated above; or a radical

- (CH₂)₀— N N

^ ' ^R18 wherein Ri₇ and Ri₈ are Ci-C₄alkyl or Ci-C₄alkyl substituted by OH; R₃' and R₉' can have additionally the meaning of hydrogen.

10. An oral care composition according to claim 9 wherein R₆' is hydroxy.

11. An oral care composition according to claim 1 wherein the peroxy compound is selected from the group consisting of hydrogen peroxide, peroxyacids and their salts, peroxydiphosphate, urea peroxide, metal peroxides, and the salts of perborate, persilicate, perphosphate, percarbonate and mixtures thereof.

12. An oral care composition according to claim 1 wherein the further adjuvant is selected from the group consisting of water, pharmaceutically acceptable carriers, anionic, nonionic, amphoteric surfactants, particulate abrasive materials, humectants, binders, thickeners, flavors, preservatives, opacifying agents, coloring agents, pH-adjusting agents, sweetening agents, stabilizing compounds, anti-bacterial agents, anti-inflammatory agents, anti-caries agents, plaque buffers, vitamins, desensitizing agents, buffers, liposomes, anti-calculus agents and mixtures thereof.

13. A method of whitening stained or discolored teeth in the oral cavity which comprises applying to the teeth an oral care composition according to claim 1.

14. A method of whitening stained or discolored teeth in the oral cavity which comprises applying to the teeth in a first step a) a compound of formula (1 ) according to claim 1 and in a second step b) a peroxy compound optionally with further adjuvants.

15. Use of a compound of formula (1 ) according to claim 1 together with a peroxy compound for the whitening of teeth.