WO2001064175A1 - Produits de blanchiment des dents et procedures associees - Google Patents

Produits de blanchiment des dents et procedures associees Download PDF

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Publication number
WO2001064175A1
WO2001064175A1 PCT/EP2000/010698 EP0010698W WO0164175A1 WO 2001064175 A1 WO2001064175 A1 WO 2001064175A1 EP 0010698 W EP0010698 W EP 0010698W WO 0164175 A1 WO0164175 A1 WO 0164175A1
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Prior art keywords
enzyme
teeth
bleaching
laccase
composition according
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PCT/EP2000/010698
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English (en)
Inventor
Lucas Huybrechts
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Lucas Huybrechts
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Priority claimed from BE2000/0166A external-priority patent/BE1013335A6/nl
Priority claimed from BE2000/0293A external-priority patent/BE1013402A7/nl
Priority claimed from BE2000/0470A external-priority patent/BE1013604A6/nl
Application filed by Lucas Huybrechts filed Critical Lucas Huybrechts
Priority to AU79242/00A priority Critical patent/AU7924200A/en
Publication of WO2001064175A1 publication Critical patent/WO2001064175A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A61K8/496—Triazoles or their condensed derivatives, e.g. benzotriazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/66—Enzymes

Definitions

  • Tooth whitening products and procedures Tooth whitening products and procedures.
  • the present invention relates to a new multi-stage-multi-active-agent-whitening procedure for teeth, comprising the use of novel enzymatic and novel chemical whitening formulations; it also comprises the use of novel stain weakening enzymatic formulations, resulting in stain components that exhibit an increased response to whitening by oxidative whitening chemicals.
  • the new whitening agents can also be used in single stage whitening procedures.
  • Extrinsic stains can be caused by bacterial debris, build-up of glycoproteines, and precipitation of chromophoric molecules .
  • Other sources involve degradation products from blood, hemoglobuline and sulfur containing proteins or the use of medicines that contain chlorhexidine, iron, mangan or silver containing compounds.
  • extrinsic stains are foods such as coffee, wine, tee or certain fruits (cherries, resins).
  • foods such as coffee, wine, tee or certain fruits (cherries, resins).
  • lipophilic polyphenolic food ingredients easily form complexes with proteins and starches and precipitate on the surface of teeth, to form yellow brown stains. Over time they can penetrate deeper into fissures and be very difficult to remove. Also nicotine and tar from cigarettes and cigars contribute to the staining process.
  • At least part of the extrinsic stains can be removed successfully by abrasives and mechanical brushing; bleaching compositions, either with chemicals or enzymatic bleaching agents, can help though.
  • Intrinsic stains may have endo genie causes; they may be the result of degradation products from the body such as blood, consumption of tetracycline's, fluorides, or intake of food components that reach the teeth from the blood vessels. They can also be caused by certain diseases such as sickle-eel anemia, thalassemia and diseases of kidney or liver. These stains can only be removed by agents able to penetrate into the teeth.
  • the whitening performance and the required number of treatments depends primarily on the peroxide concentration. As home bleaching products have relative low dosages of peroxide, frequent repetition of treatments over many days and even weeks is required, before whitening appears and carbamide peroxide concentrations below 10 % show modest performance anyhow. Peroxides become more effective at higher concentration but simultaneously toxicity goes up and side-effects surface. Kwong et al. (NZ Dent. J. 89: 18-22,1993) observed a moderate inflammatory pulpal response in teeth extracted after application of carbamide peroxide over a period of two weeks. Cherry et al. (J.Dent.Res. 72:1298-1303,1993) showed that ingestion of carbamide gel ( 10 % to 35 %) resulted in toxic effects in female rats.
  • Peroxides are especially keen to oxidize saccharides.
  • peroxides irritate gums and throat, react with essential amino acids and with dental restorative materials. Regularly, patients perceive their teeth as painful and sensitive after a bleaching session.
  • Any effective enzymatic treatment will therefore require the use of a variety of different types of enzymes, all attacking specific ingredients of the stain, until it can totally disappear. Only a multi-enzyme treatment procedure can exhibit the potential of combining high bleaching efficiency and safety.
  • WO 99/25315 patent application claims whitening capabilities for a toothpaste comprising the papain enzyme from the papaya plant.
  • Japanese patent application JP08157352 claims the use of a broad range of cleaning compositions comprising a thiol containing protease in a deactivated form; deactivation is said to improve shelf life and storage stability.
  • WO97/06775 and US5989526 claim compositions comprising oxido-reductases, in particular laccases in combination with an activating co-ingredient, that are able to whiten teeth in a one-stage treatment procedure.
  • the main advantage of the invention is the discovery of new bleaching procedures for teeth that provide the desired combination of increased whitening efficiency with enhanced safety standards as a result of the use of very low concentrations of active agents.
  • Fig.1 contains data from experiment 3.
  • the y-axis shows the increase in blue pixels resulting from the bleaching experiment.
  • the x-axis shows the five consecutive bleaching treatments on two teeth halves.
  • Fig.2. contains data from experiment 4.
  • the y-axis shows the increase in blue pixels resulting from a bleaching treatment.
  • the x-axis shows four consecutive bleaching treatments on two teeth halves.
  • Fig.3. contains data from experiment 5.
  • the y-axis shows the increase in blue pixels resulting from a bleaching treatment.
  • the x-axis shows two consecutive bleaching treatments on two teeth halves.
  • Fig.4. contains data from experiment 7.
  • the y-axis shows the increase in blue pixels from a bleaching treatment.
  • the x-axis shows the dioxirane treatments (1 and 2) and the hydrogen peroxide treatment (3).
  • a whitening composition is a formulation that has the capability, by action of physical contact, to enhance the degree of whiteness of teeth.
  • a stain weakening composition has the ability to change the molecular structure of stain components (without actually changing the degree of whiteness of the tooth), resulting in an enhanced response of the stains during the next and separate treatment stage with a whitening oxidation chemical, such as hydrogen peroxide.
  • a pre-treatment with a "stain weakening composition” acts synergistically upon the next treatment stage and will enhance the performance in the next and separate treatment stage of the whitening formulation with the oxidation chemical.
  • Single stage refers to a procedure where the teeth are subjected to only one bleaching composition and the total whitening procedure consists of only one treatment step (or stage).
  • Teeth are exposed to two or more bleaching steps (or stages) that are carried out separately, one step after the other. In every treatment step the teeth are exposed to a composition.
  • the different treatment steps may comprise the use of an identical composition. Hence, exposure of teeth to this composition is repeated. This is called “multistage-mono-active-ingredient-bleaching procedure” .
  • the steps may comprise the use of different non-identical formulations, with different active ingredients, which is called a “multi-stage- multi-active-agent-bleaching procedure.
  • the formulations may refer to "whitening"- as well as “stain weakening compositions”.
  • Whitening and stain weakening compositions can be administered to teeth in a variety of delivery forms: tooth paste, gel formulation for use in a plastic tray that covers teeth, mouth washes, dental creams , dental cleaning agents, chewing gum, patches.
  • Each delivery system is specific in terms of ingredients, concept of administration to teeth, and contact time.
  • a toothpaste typically contains 10 to 70 % abrasive ingredients, is applied by a tooth brush and the contact time is seconds up to a few minutes.
  • a whitening gel does not contain an abrasive, it is applied by a plastic tray that covers the set of teeth and the treatment time can be as long as the whole night.
  • composition means the arrangement of physical contact between a composition and teeth, in the form of a selected delivery system and for a selected treatment time period.
  • This invention is about novel innovative whitening products, based on enzymatic and non-enzymatic active ingredients; products that, when used together within the context of a "multi-stage-multi-active-agent-bleaching-procedure", exhibits a better bleaching performance and superior safety conditions, as when compared to the use of traditional whitening products such as hydrogen peroxide or carbamide peroxide.
  • a method for the measurement of the degree of whiteness has been developed.
  • the whiteness of teeth is assessed either by visual inspection (comparison with standard teeth having different degrees of colouration; Vitapan shade guide index) or by means of diffuse reflectance spectrophotometry (L*a*b*).
  • the first method has limitations.
  • the base-colour i.e. the colour that is uniformly spread over the total surface
  • Bleaching agents do not necessarily exhibit similar bleaching capabilities on different types and parts of the stain and a differentiation cannot be made accurately since the shade standards (made from glass-ceramic material) are coloured uniformely. Identification of a colour change in a local stain spot is difficult to carry out.
  • the second method suffers from the same limitation .
  • An average degree of whitening can though be measured for a particular part of the tooth. It is however not straightforward to position the tooth on the measuring device in such a way that always the same part of the tooth is under analysis.
  • Prof C. Bently et al. J.Amer.Dent.Assoc. vol 130/06,1999,809 has demonstrated the possibility to monitor changes in tooth brightness with photographic equipment. They discovered a good relationship with the mean pixel intensity for the RGB blue channel (MPI-b) on a picture. This is of no surprise because blue is the opposite colour of yellow, the dominating colour of stains on teeth.
  • This parameter appears to provide a better brightness descriptor than when using reflectance spectrophotometry and better correlation with the Vitapan shade guide.
  • a sensitive digital camera Nikon coolpix 990.
  • the enzyme tannase (tannin acylhydrolase ED 3.1.1.20) is capable of increasing the whiteness of teeth.
  • Extrinsic stains are a mix of bacterial debris, proteins and polymeric polyphenolic structures, which are very difficult to remove.
  • the strategy is to break down polymeric material and complexes , either by hydrolyses or oxidation. The smaller the compounds become, the more readily they will disappear from the teeth.
  • Exp. 1 demonstrates it's ability to increase whiteness from 13 to 38 blue pixels (change of MPI-b) especially on local stain spots on the tooth surface.
  • Tannase can be used within a pH range of 2 to 9, preferably 4 to 7 and a reaction temperature between 0 C and 80 C, preferably 35 C to 45 C.
  • the enzyme concentration and activity can be anything (without limitation) and may vary widely between below 1 U/ml to more than a couple of thousand units/ml bleaching formulation.
  • the Unit of Activity is according to the suppliers method (Kikkoman Corp.).
  • Tannase may be derived from a traditional source such as Asp.oryzae or from other sources or may be genetically engineered.
  • Tannase should preferably (but not necessarily) be used in combination with activating co-ingredients such as EDTA, cysteine and a thiol containing molecule (e.g. mercaptoethanol). Concentrations may vary widely, but 0.25 % EDTA 0.5 % cysteine and 0.03% mercaptoethanol w/w in the bleach formulation are indicative.
  • the treatment with tannase can preferably be preceded by a treatment with the papain enzyme.
  • the enzyme can be used within a formulation that does not contain another bleaching agent; as such it can be used as an enzyme bleaching step in a "multistage-multi-active-agent-bleaching" procedure. It can also be used in a formulation that contains other bleaching agents such as oxido reductases (in particular laccases), proteases (papain), lyzozyme, or in combination with traditional chemical oxidizing agents such as hydrogen peroxide, carbamide peroxide, sodium perborate, ... Papain
  • the papain enzyme demonstrates substantially enhanced bleaching activity, when activating co-ingredients are added to the bleaching composition.
  • patent application W099/25315 claims whitening capabilities for a toothpaste comprising the papain enzyme from the papaya plant, we have discovered, surprisingly, a new formulation comprising the papain enzyme, but having far greater whitening capabilities compared to W099/25315, due to the presence in our formulation of co-ingredients that have the ability to boost the enzyme's whitening activity.
  • a whitening formulation comprising the papain enzyme and it's activating co-ingredients
  • This procedure allows longer treatment times (hours) compared to the use of toothpaste (minutes) and this further increases the whitening capabilities.
  • Gels and toothpastes are different technologies, having completely different ingredients and serve a different purpose.
  • the gel/tray delivery system has not been described in patent application W099/25315.
  • Japanese patent application JP 08157352 describes formulations for use in a broad range of cleaning applications (bath preparations, toothpaste, general cleaners) and comprising thiol-containing proteases that have been added in a deactivated form in order to achieve improved shelf life during storage.
  • the enzyme is said to regain activity during the use of the formulation as a result of the occurrence of small amounts of products such as cystine in the water, originating and released from the living body.
  • the patent does not mention formulations comprising the addition of products such as cysteine, EDTA, thiol containing products; the patent does not mention the application of tooth whitening or the effect of the co-ingredients on tooth whitening performance, nor does it refer to the use of a gel/tray delivery systems, a preferred system for whitening products.
  • the patent does not describe compositions comprising activated proteases whereas our formulations comprise activated papain.
  • our whitening formulation and preferred delivery system offers superior whitening performance compared to existing formulations and none of the formulations known in the public domain for use as whitening compositions are using papain in combination with activating ingredients.
  • Experiment 2 demonstrates a whiteness increase of 14 blue pixels when using a bleaching formulation with papain as well as additional activating co- ingredients, and no pixel increase when activating co-ingredients where not present. In another part of the experiment, respectively the values 9 and 3 blue pixels have been obtained.
  • the papain latex from the Carica papaya plant contains broadly active proteases, lyzozyme and esterase's. It does whiten both the basic colour of the teeth as well as local stains. It's action is supported by the use of tannase. Suitable concentrations for activating ingredients are 0.25 % EDTA, 0.5 % cysteine hydrochloride and 0.03% mercaptoethanol. Other concentrations can be used effectively. Mercaptoethanol can be replaced by other thiol containing compounds (e.g. dithiotreitol); metabisulfite salts and N-bromo-succinimide can also contribute to the activation process.
  • thiol containing compounds e.g. dithiotreitol
  • metabisulfite salts and N-bromo-succinimide can also contribute to the activation process.
  • the papain enzyme can be used between a pH range of 4 and 9, preferably 6 to 8; it is active between 10C and 80 C.
  • concentration of papain may vary widely.
  • An appropriate (but not limiting to) concentration is 50 mg papain / 10 ml bleaching solution from an enzyme with 30.000 USP/mg activity. Other concentrations and activities can be used too.
  • the performance of bleaching formulations with papain & co-ingredients varies with the tooth sample; MPI-b changes between 12 and 40 pixels have been found. In most cases a repetition of the papain treatment provides an additional whiteness gain.
  • Papain may be replaced by proteases from other sources, but they are less reactive. Papain (and it's activation co-ingredients) may be used in a formulation and this eventually in conjunction with other enzymes such as tannase, laccase, other oxido-reductases, lyzozyme, ....or mixed with classical oxidizing agents.
  • papain can be used in toothpastes, it is preferable to use delivery systems that allow a longer treatment time such as bleaching gels (for use with trays) or ready made patches loaded with an enzymatic bleach composition.
  • Patent WO97/06775 and US5989526 claim the use of a formulation comprising an oxido-reductase enzyme for whitening of teeth in a one stage treatment procedure.
  • laccases are contemplated and an additional co-product, so-called “mediator” is added to improve the bleaching performance.
  • the whitening is resulting from the direct contact of the enzyme and/or mediator with the stains on the teeth.
  • laccase/HBT do not whiten teeth at all.
  • laccase/HBT combination can be used for another interesting property.
  • a treatment with laccase/HBT changes the chemical structure of stain components (without whitening).
  • the laccase/HBT pre-treatment has weakened the structure of the stain components in such a way that the stain itself has become more vulnerable towards a subsequent whitening treatment step with an oxidation chemical such as hydrogen peroxide, carbamide peroxide or dioxirane.
  • tooth A and B are different teeth. Peroxide treatments provide tooth A with the highest increase in whiteness only in bleach procedures where A has also been subjected to a laccase pre-treatment. In cases where A and B, both, have been treated or not have been treated with laccase, A isn't whitening more than B.
  • laccase/HBT can be used effectively as a "stain structure weakener" in a multi-stage-bleaching-procedure.
  • a multistage bleaching process comprising at least two steps or more in which a peroxide bleaching step is preceded with a laccase/HBT treatment in order to take advantage of the synergy.
  • Laccase can be used in a concentration between 0.0001% and 25 % based on end weight of the bleaching formulation.
  • the pH can be between 4.5 and 9, preferably between 4.6 and 7.5.
  • Laccase can be supplemented with other enzymes such as tannase, glucoseoxidase or oxidoreductases such as Mn peroxidase.
  • the laccase solution can further be saturated with oxygen.
  • the laccase can be obtained from every known source such as for example Collybia, Fomes, Lentinus, Pleurotus, Aspergilus, Neurospora, Podospora,
  • dioxiranes are able to whiten teeth. They are composed of a three-atom-membered ring structure with two oxygen and one carbon atom. They are strong oxidizers (dimethyldioxirane is ten-fold more reactive compared to hydrogen peroxide).
  • Experiment 7 shows the effectiveness of dimethyldioxirane at dosages substantially lower than in use for hydrogen peroxide.
  • First dioxirane treatment delivered a rise with 29 blue pixels and in another occasion (experiment 8) 28 blue pixels.
  • Dioxiranes can be made in situ from a ketone catalyst and oxone (ref Curci et al., J. Org. Chem., 1980, 45, 4758; Kurihara et al, tetrahedron Lett., 1994, 35, 1577 ;Denmark et al, J.Org. Chem., 1995, 60 ,1391 ; Yang et al., J.Org. Chem. 195,60,3887). Production preferably is carried out between 0C and 40 C; The pH is between 6 and 8, preferably around 7 and a buffer such sodium carbonate (or caustic soda) is used to neutralize the acid of oxone.
  • a buffer such sodium carbonate (or caustic soda) is used to neutralize the acid of oxone.
  • the reaction is carried out in water and an appropriate ketone should be used such as acetone, cyclohexanone, 1 ,4-cyclohexane-dione, cyclic ketones with more than one cyclic ring structure or bis(triethylphosphine)-platinum (I ⁇ )-oxalate.
  • an appropriate ketone such as acetone, cyclohexanone, 1 ,4-cyclohexane-dione, cyclic ketones with more than one cyclic ring structure or bis(triethylphosphine)-platinum (I ⁇ )-oxalate.
  • concentrations are used in a preferred enbodiment: 2mmole sodium carbonate /10 ml , 1.5 mmole oxone /10 ml and 2 mmole keton /10 ml bleaching formulation. Other concentrations can be used.
  • dioxiranes provide a means to reduce the total chemical exposure (dioxiranes act at lower concentrations than hydrogen peroxide), and provide an increase in selectivity towards attack of lipophilic stain components.
  • Multi-stage-multi-active-agent-bleaching-procedure In the unifying aspect of the invention a "multi-stage-multi-active-agent- bleaching-procedure" is claimed with better whitening capabilities compared to peroxides thanks to, 1. a synergistic action between enzymes and chemical oxidizing agents,
  • Tannase, dioxirane and laccase do act on lipophilic moieties and contribute to complete removal of these stain spots.
  • a procedure that includes the use of enzymes is able to provide more complete whiteness compared to the use of hydrogen peroxide or carbamide peroxide.
  • Papain and activating co-ingredients act predominantly on hydrophylic segments, (proteins, bacterial debris); tannase chops gallic acid from taninic components such as gallocatechins and proanthocyanidins.
  • papain and tannase enzymes can be repeatedly used in an alternating procedure; they will exert a positive influence on each others action as they "clean" the site for the next enzyme.
  • Laccase/HBT continues the attack on phenolic segments of the remaining part of tanninic structures. At this stage the stains are partly removed and the remainder is weakened in such a way that lower amounts of oxidation agents (if needed at all) are sufficient to reach full whiteness. At this stage either a classical peroxide or dioxirane can be used.
  • Another important aspect of the invention is the possibility to drastically reduce the chemical exposure, improving safety standards further.
  • Even a treatment with a rather low amount of hydrogen peroxide entails an exposure to teeth with approximately 1.5 mole/1.
  • the chemical exposure from enzymes will be a factor 10.000 and more lower compared to peroxide, on the basis of available active molecules.
  • a 9% w/w composition with oxone contains only 10 % from the mole concentration of a 5 % hydrogen peroxide solution. It is to be expected that the dioxirane concentrations will still be substantially lower than the initial oxone concentration.
  • any multi stage bleaching procedure taking advantage of enzymes and or dioxiranes will be safer, compared to the sole use of peroxides, not only because of the lower levels of chemical exposure, but also because enzymes act predominantly on the surface of teeth and not inside.
  • the bleaching and stain weakening formulations can be delivered in a variety of "delivery systems". Examples are gel formulations for use in a plastic tray , toothpaste, dental creams, mouth washes, denture cleaning agents, chewing gum, patch based systems.
  • whitening and stain weakening gel formulations for loading into a dental tray designed for placement over teeth such that the bleaching composition will contact the tooth surface.
  • This system allows prolonged contact times between the gel formulation and the teeth, further improving the effectiveness of the whitening gel in a substantial way.
  • Normal practice entails contact times between 10 minutes up to a few hours and up to complete overnight treatment. Toothpaste whitening formulations exhibit much shorter contact times (seconds to minutes only) and this does not favor an optimal enzymatic whitening performance.
  • gel formulations for use in a plastic tray
  • a thickener such as carbopol, xanthan gum, starch, alginates, pectin, cellulose derivates, polyacrylic acid and salts
  • a pH adjusting agent such as calcium carbonate, caustic soda,..
  • a chelating agent such as EDTA
  • a humectant such as glycerol, polyol, sorbitol, polyethylene glycol, propylene glycol, 1,3 propanediol, 1,4 butanediol, hydrogenated and hydro lysed polysaccharides
  • a sweetener such as saccharine
  • flavors perfume
  • antibacterial agents such as chlorhexidine digluconate
  • the gel formulation may e.g. comprise between 0.1 % and 20 % thickener (w/w); ingredients such as a chelating agent, a sweetener, flavor, perfume, an anti-bacterial agent may e.g. be present in amounts between 0 % and 5% .
  • the concentration of humectant can be between 0 and 80 %.
  • the delivery systems may be of the "one compartment type" but also included in the invention are the two-compartment formulations; for example the "stain weakening" delivery system may e.g. consist of two formulations: a laccase formulation and a formulation with the mediator for mixing just before use. Equally the dioxirane delivery system may e.g. consist of a formulation with oxone and another formulation with the keton catalysts and the pH modifying ingredient, for mixing just before use.
  • the bleaching and stain weakening formulations may be included in products for use by professional dentists in office, or may be part of "dentist prescribed but home used” products.
  • the bleaching and stain weakening formulations may be added to abrasive creams for use by the dentist.
  • Abrasive polishing material may include alumina based products, magnesium trisilicate, magnesium carbonate, sodium and calcium bicarbonate, kaolin, aluminosilicates, zirconium silicates, calcium pyrophosphate, other phosphates , hydroxyapatite, powdered plastics such as polyvinylchloride, polyamides, polymethyl methacrylate, polystyrene, phenol-formaldehyde, melamine formaldehyde, urea formaldehyde resins, epoxy resins, silica xerogels, and the like.
  • Anti-bacterial agents can be added such as chlorhexidine digluconate, hexetidine, alexidine, quaternary ammonium compounds, metal ions such as zinc, copper, silver, and stannous chloride.
  • Teeth react differently to bleaching agents. Even teeth with similar degrees of staining exhibit a wide variation in response. This is why teeth samples have been cut into two halves and the cut surface has been closed with an acrylate layer, enabling us to do comparative studies on tooth halves with similar properties. Cutting along the long axis of the tooth, in mesio-distal or bucco lingual direction has been performed. All tooth parts are large enough for close analyses with the digital photographic method. Staining. Some tooth samples have been stained on purpose by submerging in a 10 ml mixture of chlorohexidine di gluconate (0.5 % w/w), tea and coffee components, and human saliva. Samples have been submerged five times at room temperature for a period of one day and have been dried in between by air. Determination of tooth colour by mean blue pixel value.
  • the degree of whiteness can be determined by measuring the mean blue pixel intensity (MPI-b) on a picture according to the method of Prof. C. Bently (1999). It appears that MPI-b exhibits a better correlation with the Vitapan shade guide than data from reflectance spectrophotometry.
  • the difference MPI-b between the standard tooth 1M1 and 5M3 is approximately 100 pixels.
  • Tooth samples have been stored in deionised water. Just before taking the picture, the water on the surface has been removed by a paper towel; the picture was immediately taken within ten seconds.
  • Laccase is from trametes hirsuta and has an activity of 14000 nkat/ml.
  • 1 Unit (16.7 nkat) is the amount of enzyme that catalyses the conversion of 1.0 ⁇ mole ABTS per minute at pH 4.5.
  • Tannase enzyme is from Asp. Oryzae and has an activity of 5000 U/mg (supplier
  • Papain enzyme is from Carica papaya L and has an activity of 30.000 USP
  • U/mg. 1 Unit is the activity that releases the equivalent of one ⁇ g of tyrosin from a specified casein substrate at 40 C, pH 6 and within 60 minutes period.
  • Tooth samples have been subjected to a treatment with the tannase enzyme (tannin acylhydrolase EC 3.1.1.20) having an activity of 5000 U/gr (determination of activity according to the supplier Kikkoman).
  • the 10 ml aliquot contained a citrate buffer at pH 5 or 4.7 as well as 0.2 % EDTA, 0.45 % cysteine hydrochloride and 0.0025 % mercaptoethanol. Temperature was 37C and reaction time 2 hours.
  • the tannase acts predominantly on these yellow/brown spots.
  • the colour reduction can be seen by visual inspection as well as measured in average mean blue pixel intensity MPI-b.
  • the amount of acid present (pH 5) is too low to account for a contribution to the whitening process.
  • Pixel values for untreated halves are 119 (A) and 132 (B) (standard teeth from the "Vitaplan 3D-master tooth colour guide” have 136 (4M3) and 102 (5M3) pixels.
  • the whiteness increase of tooth halve A is superior to B, due to the presence of activating co-products in the bleach formulation.
  • Laccase treatment 15 ml buffer pH 4.8 (citrate; Sigma) 10 minutes saturation with oxygen gas, hydroxybenzotriazole 4mM, 8.5 to 12 U hirsuta trametes laccase, 38 C, 2 hours.
  • Fig.l and the table show the pixel gains from the peroxide treatment steps only:
  • the extra whiteness gain for tooth A over B is 26%, 44 % and + 100 % (per step).
  • a tooth has been cut in two parts and the cut surface has been closed with a polyacrylate layer.
  • the left tooth halve (ref Fig. 2) has been subjected to pre-treatments with laccase before bleaching with hydrogenperoxide ( in steps 2,3 and 4).
  • the right tooth halve has not been subjected to a laccase treatment.
  • Peroxide treatment 22 mg EDTA, 4.6 % w/w H202, pH 7.4, 35-40 C, 2 hours.
  • Laccase treatment 15 ml buffer pH 4.8 (citrate; Sigma) 10 minutes saturation with oxygen gas, hydroxybenzotriazole 4mM, 8.5 to 12 U hirsuta trametes laccase, 38C, 2 hours.
  • the left tooth halve (ref. Fig. 3) has been subjected to a pre-treatment with laccase before bleaching with hydrogen peroxide in step 2 only.
  • the right tooth halve has not been subjected to a laccase treatment.
  • Peroxide treatment 22 mg EDTA, 3.5 % (stage 1) and 4.6 % (stage 2) w/w H202, pH 7.5, 35-40 C, 2 hours.
  • Laccase treatment 15 ml buffer pH 4.8 (citrate; Sigma) 10 minutes saturation with oxygen gas, hydroxybenzotriazole 4mM, 8.5 to 12 U hirsuta trametes laccase, 38C, 2 hours.
  • the bleaching result of the left tooth is superior in stage 2, thanks to the laccase pre-treatment.
  • the tooth has been cut in two halves and the surface has been closed with a polyacrylate layer.
  • the halves have kept their natural staining condition.
  • the whiteness values of the halves are 94 and 96 blue pixels ( to be compared with 4M3: 123, 5M3: 90 standard teeth from the VITAPAN shade guide).
  • the left tooth halve has been subjected to a pre-treatment with laccase before bleaching with hydrogen peroxide in both steps (1,2).
  • the right tooth halve has not been subjected to a laccase treatment.
  • Peroxide treatment 22 mg EDTA, 4.9 % (stage 1) and 6 % (stage 2) w/w H202, pH 7.5, 38-40 C, 2 hours.
  • Laccase treatment 15 ml buffer pH 4.8 (citrate;Sigma) 10 minutes saturation with oxygen gas, hydroxybenzotriazole 4mM, 8.5 to 12 U hirsuta trametes laccase, 38C, 2 hours.
  • the whiteness increase of tooth halve A is superior to B thanks to the pre- treatment with laccase.
  • a tooth with natural stains (whiteness value: 142; standard teeth 3M3 : 163 and 4M3: 138) has been subjected to two dioxirane treatments and one hydrogen peroxide bleaching step.
  • the dioxirane treatment has been carried out in 10 ml deionised water with Na2C03.10H2 (550 mg or 985 mg), oxone (920 mg or 1380 mg) and acetone (100 mg and 150 mg) (amounts respectively used in the first and second dioxirane treatment) .
  • the dimethyl dioxirane is improving the whiteness with more than one standard tooth shade in the first treatment (29 blue pixels). See also Fig. 4 Experiment 8(dioxirane
  • a tooth sample with a high whiteness value has been subjected to one dioxirane treatment (10 ml, 570 mg Na2C03.10H20, 920 mg oxone, 100 mg aceton, gradual temperature rise from 5 C to 37 C over 2.5 hours.
  • the novel agents have been used in a multi stage bleaching procedure.
  • the aim is to bleach teeth to full whiteness and at the same time reducing the chemical exposure to a level below the one traditionally used with hydrogen peroxide and carbamide peroxide. This enables to combine bleaching efficiency with enhanced safety procedures.
  • Acid treatment has been carried out with a citrate buffer at pH 5 at 37 C for 2 hours.
  • the papain bleaching formulation (10 ml deionised water) contained 50 mg refined papain, 0.2 % EDTA, 0.45 % cysteine and 0.0025 % mercaptoethanol; reaction at 38C for 2 hours.
  • the tannase treatment was carried out in 10 ml citrate buffer pH 5 in the presence of 0.2 % EDTA, 0.45% cysteine, 0.0025% mercaptoethanol and 50 to
  • the solution has been saturated with oxygen for a period of 10 minutes; reaction at 38 C for 2 hours.
  • Dimethyldioxirane has been prepared in 10 ml deionised water; at 5 degrees C
  • Hydrogen peroxide has been prepared in 10 ml aliquots of water with 22 mg
  • Tooth halves Al and A2 (same tooth)
  • Whiteness value Al 156
  • Whiteness value standards 1M1 190 at start A2: 157 Vitapan shade 3M3: 162
  • Whiteness value B 159
  • Whiteness value standards IMl 192 at start 3M3: 164 4M3: 141
  • Whiteness value C 101
  • Whiteness value standards IMl 192 blue pixels at start 4M3:141 5M3.111
  • Whiteness value D 130
  • Whiteness value standards IMl 196 Vitapan shade guide 2L2.5: 173
  • the examples demonstrate that a substantial part (and often the total part) of the desired whiteness gain can be achieved with enzymes, in particular with "papain & activating co-ingredients", tannase and the laccase enzyme.
  • the total chemical exposure, and in particular the one from oxidizing agents has been decisively reduced, adding to the safety standard of the procedure.

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Abstract

L'invention se rapporte à une procédure de blanchiment 'multi-étape' pour les dents, selon laquelle plusieurs types nouveaux et différents d'agents de blanchiment et de réduction des tâches sont utilisés de manière consécutive, lesdits agents produisant dans leur ensemble des résultats de blanchiment supérieurs et perfectionnés (jusqu'à l'obtention de dents parfaitement blanches), et ce dans des conditions de niveaux considérablement réduits d'exposition chimique des dents, en comparaison des procédures de blanchiment classiques basées sur l'utilisation de peroxydes. Il s'avère notamment que l'enzyme tannase, ainsi que les dioxiranes, peuvent blanchir efficacement les dents; que les résultats de blanchiment avec l'enzyme papaïne peuvent être considérablement améliorés en présence de co-ingrédients sélectionnés; et qu'un prétraitement avec une enzyme laccase améliore les résultats de blanchiment d'un agent chimique d'oxydation lors d'une étape de blanchiment ultérieure. Ces nouvelles procédures permettent toutes deux d'obtenir des résultats de blanchiment incomparables, dans des conditions satisfaisant des normes de sécurité renforcées et sans égales.
PCT/EP2000/010698 2000-03-01 2000-10-26 Produits de blanchiment des dents et procedures associees WO2001064175A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU79242/00A AU7924200A (en) 2000-03-01 2000-10-26 Tooth whitening products and procedures

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
BE2000/0166A BE1013335A6 (nl) 2000-03-01 2000-03-01 Werkwijzen en produkten voor het bleken van tanden.
BE2000/0166 2000-03-01
BE2000/0293 2000-04-26
BE2000/0293A BE1013402A7 (nl) 2000-04-26 2000-04-26 Formuleringen met tannase enzym voor het bleken van tanden.
BE2000/0470A BE1013604A6 (nl) 2000-07-27 2000-07-27 Formuleringen met dioxiranen voor het bleken van tanden.
BE2000/0470 2000-07-27

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1203576A1 (fr) * 2000-11-03 2002-05-08 Clariant GmbH Composition pour le nettoyage de prothèses dentaires
WO2004028497A1 (fr) * 2002-09-24 2004-04-08 The Boots Company Plc Procede permettant d'ameliorer l'aspect des dents
RU2494725C1 (ru) * 2012-08-20 2013-10-10 Общество С Ограниченной Ответственностью "Сплат-Косметика" (Ооо "Сплат-Косметика") Минерально-ферментативный комплекс для укрепления и отбеливания эмали зубов, композиция для гигиены полости рта и зубная паста
US8933147B2 (en) 2005-11-17 2015-01-13 3M Innovative Properties Company Anti-microbial dental impression material
JP2015502362A (ja) * 2011-12-19 2015-01-22 コルゲート・パーモリブ・カンパニーＣｏｌｇａｔｅ−Ｐａｌｍｏｌｉｖｅ Ｃｏｍｐａｎｙ 酵素触媒反応を提供するシステム
EP2968084A4 (fr) * 2013-03-14 2016-08-10 3 In 1 Dental Pllc Compositions de traitement de la xérostomie et de traitement des dents
US9884000B2 (en) 2011-12-19 2018-02-06 Colgate-Palmolive Company Peracid-generating compositions
US10098824B2 (en) 2011-12-19 2018-10-16 Colgate-Palmolive Company System providing perhydrolase-catalyzed reaction
US10258546B2 (en) 2011-09-14 2019-04-16 Colgate-Palmolive Company Tooth whitening strip
WO2021089581A1 (fr) 2019-11-04 2021-05-14 Universitat Autonoma De Barcelona Composition de blanchiment des dents
EP4385491A1 (fr) * 2022-12-14 2024-06-19 SkyLab AG Composition biotechnologique stable au ph à base de laccase pour la dégradation ciblée de mélanoidines colorées et/ou de composés organiques phénoliques sur des surfaces denses

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DE1944904A1 (de) * 1969-09-04 1971-04-01 Uwe Dr Wolf Verfahren zur Reinigung von Geschirr und Waesche
FR2345998A1 (fr) * 1976-04-02 1977-10-28 Manceau Laboratoires Perfectionnement apporte aux dentifrices
WO1997006775A1 (fr) * 1995-08-18 1997-02-27 Novo Nordisk A/S Blanchiment des dents
GB2304107A (en) * 1995-08-08 1997-03-12 Ciba Geigy Ag Enzyme activity enhancement by addition of an (hetero)aromatic compound
WO1997011676A1 (fr) * 1995-09-25 1997-04-03 Robert Eric Montgomery Compositions pour blanchir les dents

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE1944904A1 (de) * 1969-09-04 1971-04-01 Uwe Dr Wolf Verfahren zur Reinigung von Geschirr und Waesche
FR2345998A1 (fr) * 1976-04-02 1977-10-28 Manceau Laboratoires Perfectionnement apporte aux dentifrices
GB2304107A (en) * 1995-08-08 1997-03-12 Ciba Geigy Ag Enzyme activity enhancement by addition of an (hetero)aromatic compound
WO1997006775A1 (fr) * 1995-08-18 1997-02-27 Novo Nordisk A/S Blanchiment des dents
WO1997011676A1 (fr) * 1995-09-25 1997-04-03 Robert Eric Montgomery Compositions pour blanchir les dents

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1203576A1 (fr) * 2000-11-03 2002-05-08 Clariant GmbH Composition pour le nettoyage de prothèses dentaires
WO2004028497A1 (fr) * 2002-09-24 2004-04-08 The Boots Company Plc Procede permettant d'ameliorer l'aspect des dents
US8933147B2 (en) 2005-11-17 2015-01-13 3M Innovative Properties Company Anti-microbial dental impression material
US10258546B2 (en) 2011-09-14 2019-04-16 Colgate-Palmolive Company Tooth whitening strip
US10098824B2 (en) 2011-12-19 2018-10-16 Colgate-Palmolive Company System providing perhydrolase-catalyzed reaction
JP2015502362A (ja) * 2011-12-19 2015-01-22 コルゲート・パーモリブ・カンパニーＣｏｌｇａｔｅ−Ｐａｌｍｏｌｉｖｅ Ｃｏｍｐａｎｙ 酵素触媒反応を提供するシステム
US9884000B2 (en) 2011-12-19 2018-02-06 Colgate-Palmolive Company Peracid-generating compositions
CN104812360A (zh) * 2012-08-20 2015-07-29 丝布拉特化妆品有限责任公司 用于牙釉质增强和增白的矿物酶复合物、口腔卫生组合物和牙膏
RU2494725C1 (ru) * 2012-08-20 2013-10-10 Общество С Ограниченной Ответственностью "Сплат-Косметика" (Ооо "Сплат-Косметика") Минерально-ферментативный комплекс для укрепления и отбеливания эмали зубов, композиция для гигиены полости рта и зубная паста
EA024261B1 (ru) * 2012-08-20 2016-08-31 Общество С Ограниченной Ответственностью "Сплат-Косметика" (Ооо "Сплат-Косметика") Минерально-ферментативный комплекс для укрепления и отбеливания эмали зубов, композиция для гигиены полости рта и зубная паста
WO2014031035A1 (fr) * 2012-08-20 2014-02-27 Общество С Ограниченной Ответственностью "Сплат-Косметика" (Ооо "Сплат-Косметика") Complexe de minéraux et ferments pour le renforcement et le blanchissement de l'émail dentaire, composition pour l'hygiène buccale et pâte dentifrice
US9968547B2 (en) 2013-03-14 2018-05-15 3 In 1 Dental Pllc Compositions for treatment of xerostomia and for tooth treatment
EP2968084A4 (fr) * 2013-03-14 2016-08-10 3 In 1 Dental Pllc Compositions de traitement de la xérostomie et de traitement des dents
US10413503B2 (en) 2013-03-14 2019-09-17 3 In 1 Dental Pllc Compositions for treatment of xerostomia and for tooth treatment
WO2021089581A1 (fr) 2019-11-04 2021-05-14 Universitat Autonoma De Barcelona Composition de blanchiment des dents
EP4385491A1 (fr) * 2022-12-14 2024-06-19 SkyLab AG Composition biotechnologique stable au ph à base de laccase pour la dégradation ciblée de mélanoidines colorées et/ou de composés organiques phénoliques sur des surfaces denses
WO2024126636A1 (fr) * 2022-12-14 2024-06-20 SkyLab AG Composition biotechnologique stable au ph à base de laccase pour la dégradation ciblée de mélanoïdines colorées et/ou de composés organiques phénoliques sur des surfaces denses

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