WO1997038670A1 - Compositions permettant l'elimination de la plaque dentaire - Google Patents
Compositions permettant l'elimination de la plaque dentaire Download PDFInfo
- Publication number
- WO1997038670A1 WO1997038670A1 PCT/DK1997/000163 DK9700163W WO9738670A1 WO 1997038670 A1 WO1997038670 A1 WO 1997038670A1 DK 9700163 W DK9700163 W DK 9700163W WO 9738670 A1 WO9738670 A1 WO 9738670A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- oral care
- dextranase
- mutanase
- care composition
- plaque
- Prior art date
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- 150000004677 hydrates Chemical class 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 229940099273 magnesium trisilicate Drugs 0.000 description 1
- 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
- 235000019793 magnesium trisilicate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 125000005341 metaphosphate group Chemical group 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940023486 oral product Drugs 0.000 description 1
- 239000013588 oral product Substances 0.000 description 1
- KZNNRLXBDAAMDZ-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane trihydrate Chemical compound O.O.O.O=[Al]O[Al]=O KZNNRLXBDAAMDZ-UHFFFAOYSA-N 0.000 description 1
- RARSHUDCJQSEFJ-UHFFFAOYSA-N p-Hydroxypropiophenone Chemical compound CCC(=O)C1=CC=C(O)C=C1 RARSHUDCJQSEFJ-UHFFFAOYSA-N 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000001814 pectin Chemical class 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Chemical class 0.000 description 1
- VSIIXMUUUJUKCM-UHFFFAOYSA-D pentacalcium;fluoride;triphosphate Chemical compound [F-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O VSIIXMUUUJUKCM-UHFFFAOYSA-D 0.000 description 1
- 208000028169 periodontal disease Diseases 0.000 description 1
- 229920001568 phenolic resin Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000647 polyepoxide Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000011435 rock Substances 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095688 toothpaste product Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- GFQYVLUOOAAOGM-UHFFFAOYSA-N zirconium(iv) silicate Chemical compound [Zr+4].[O-][Si]([O-])([O-])[O-] GFQYVLUOOAAOGM-UHFFFAOYSA-N 0.000 description 1
- 239000002888 zwitterionic surfactant Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
-
- 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
-
- 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
Definitions
- the present invention relates to oral care compositions and products comprising a dextranase and a mutanase, and option ⁇ ally other enzymes.
- the invention also relates to the use of the composition and product of the invention for the removal of dental plaque and preventing the formation of dental plaque.
- Dental plaque is a mixture of bacteria, epithelial cells, leukocytes, macrophages, and other oral exudate. Said bacteria produce highly branched polysaccharides which to ⁇ gether with microorganisms from the oral cavity form an adhe ⁇ sive matrix for the continued proliferation of plaque. As plaque continues to accumulate rock hard white or yel ⁇ lowish deposits arise. These deposits are called calcified plaque, calculus or tartar, and are formed in the saliva from plaque and minerals, such as in particular calcium.
- Oral polysaccharides are produced from sucrose introduced into the mouth, e . g. as a food or beverage constituent, by the action of cariogenic microorganisms, such as Streptococcus mu - tans or Streptococcus sanguis, growing in the oral cavity.
- Said oral polysaccharides comprise water-soluble dextran, having large portions of a-1,6 glucosidic linkage, and a major component of water-insoluble extracellular polysaccharides called "mutan" comprised of a backbone with a-1, 3-glycosidic linkages and branches with a-1, 6-glycosidic linkages. Mutan bind to hydroxyapatite (constituting the hard outer porous layer of the teeth) and to acceptor proteins on the /
- Mutanase Mutanases are a-1, 3-glucanases (also known as a-1, 3- glucanohydrolases) which degrade the a-1, 3-glycosidic linkages in mutan. Mutanases have been described from two species of Trichoderma (Hasegawa et al . , (1969) , Journal of Biological
- Dextranase Dextranases are a-1, 6-glucanases (also known as 1,6-a-D- glucan 6 glucanohydrolases) which degrade the a-1, 6- glycosidic linkages in dextran.
- microorganisms are ca ⁇ pable of producing dextranases, among them fungi of Penicil - lium, Paecilomyces, Aspergillus, Fusarium, Spicaria , Verticil - Hum, Helmin thosporium and the Chaet ⁇ mium genera; bacteria of the genera Lactobacillus , Streptococcus, Cellvibrio, Cyto- phaga, Brevibacterium, Pseudomonas , Corynebacterium, Arthro ⁇ bacter and Flavobacterium and yeasts such as Lipomyces star- key i .
- Dextranase 50 L from Novo Nordisk A/S produced by fermentation of strains of Penicillium lilacium. Dextranase 50 L is used in the sugar in ⁇ dustry to break down dextran in raw sugar juice or syrup. To be able to sufficiently guarantee the capability of chewing, e . g . foods, during a whole lifetime it is necessary to keep the teeth in a good condition and to obtain a good oral hygiene. This can be obtained by brushing the teeth fre- quently using toothpaste or the like. The mouth may further advantageously be rinsed with a mouth wash comprising antimi ⁇ crobial agents.
- US patent no. 4,353,891 (Guggenheim et al . ) concerns plaque removal using mutanase from Trichoderma harzianum CBS 243.71 to degrade mutan synthesized by cultivating Streptococcus mu - tans strain CBS 350.71 identifiable as OMZ 176. It is stated that the critical ingredient in dental plaque is water- insoluble polysaccharide with a-1, 3-glucosidic bonds and that such polysaccharide material termed mutan is not attacked by dextranase. Guggenheim et al . , (1972), Caries Res. 6, p. 289-297) dis ⁇ closes that the extent of the dental plaque of rats is not significantly affected by the simultaneous use of a dextranase and a 1, 3-glucanase (mutanase) .
- US patent no. 4,438,093 (The Research Foundation for Micro- bial diseases of Osaka) describes oral compositions comprising a dextranase and a a-1, 3-glucanase (mutanase) , both being pre ⁇ sent in an amount of 0.5 to 100 enzyme units per gram of said oral composition, in an enzyme unit ratio of 1:2 to 2:1.
- Said dextranase is derived from a bacteria within the genus Coryn - -bacterium and said a-1, 3-glucanase is derived from a bacteria within the genus Pseudomonas .
- GB 2,206,585 (Dental Chem Co LTD) described a teeth clean ⁇ ing agent containing hydroxyapatite as polishing agent, with a laevanase, dextranase and mutanase immobilised on the hydroxy ⁇ apatite.
- US patent no. 5,145,665 discloses a composition for the care of the mount and teeth comprising a dextranase and/or a 1, 3-glucanase for cleaving polysaccharides in the mouth.
- FR 2,651,433 (DANA) concerns dentifrice products containing a dextranase to acts on recent plaque, a mutanase to acts on old and insoluble plaque, and a mixture of other enzymes hav ⁇ ing bactericide action.
- US patent no. 5,320,830 (Proctor & Gamble) describes tooth ⁇ paste compositions for the reduction of plaque and gingivitis comprising a) a surfactant, b) an enzyme, c) chelating agent d) a fluoride source, e) a silica abrasive and d) a carrier.
- the enzyme is an endoglucanase, papain, a dextranase and/or a mutanase.
- the first object of the invention relates to an oral care composition
- an oral care composition comprising a dextranase and a mutanase both having a significant enzyme activity in the range from pH 4 to below 6.0.
- the dextranase is derived from a strain of the filamentous fungus genus Paecilomyces and the mutanase is derived from a strain of Trichoderma or Peni - cillium .
- the invention relates to an oral care product comprising an oral care composition of the invention.
- the oral care product is a toothpaste comprise a composition described in US patent no. 5,320, 830.
- the invention relates to the use of a composition of the invention or oral care product of the in ⁇ vention for preventing the formation of dental plaque or re ⁇ moving dental plaque.
- Figure 1 shows the time course of mutan hydrolysis
- Figure 2 shows hydrolysis of mutan on glass wall
- Figure 3 shows dosage response curve of mutan hydrolysis
- Figure 4 shows hydrolysis of mutan with Paecilomyces lilac- inum dextranase and/or Trichoderma harzianum mutanase within the pH range from 5.0 to 8.0.
- Figure 5 shows the plaque removing effect of dextranase and a mutanase both having a significant enzyme activity in the range from pH 4 to below 6.0.
- said oral care products di ⁇ rectly or indirectly may also have other oral care functions at the same time, e . g . prevention of dental holes or gingivi- tis.
- compositions and products prepared there from referred to in the present application comprise en ⁇ zymes and have a pH in the range from 4.0 to below 6.0.
- a suitable examples of such compositions and products are de- scribed in US patent no. 5,320,830 (Proctor & Gamble) which is hereby incorporated by reference.
- the present inventors have found that it is advantageous, when using a dextranase and a mutanase in oral care products, to use such enzymes having a pH optimum close to the pH of the oral care product in question.
- the first object of the invention is to pro ⁇ vide an oral care composition comprising a dextranase and a mutanase both having a significant enzyme activity in the range from pH 4 to below 6.0.
- a "significant enzyme activity” means that the relative en- zymatic activity of the enz; -te is above 70% in particular above 80%, especially above 9U ⁇ , of the activity at the pH op ⁇ timum.
- an improved product is obtained, as e.g. a less amount of enzyme need to be used to obtain the desired effect and/or less time is need to obtain the desired effect.
- the reduced amount of enzyme needed is of commercial inter ⁇ est for oral care product manufactures as the cost of produc ⁇ ing such product according to the invention can be reduced. Further, if the original amount of enzymes are added to the product an improved product can be obtained.
- dextranase and mutanases being of e . g. of microbial, such as bacterial or fungi origin, or plant origin, having a pH optimum within pH 4.0 to below 6.0, are contemplated according to the invention and therefor encompassed by the scope of the present invention.
- the dextranase may be derived from a strain of the filamentous fungus genus Paecilomyces, in particular a strain of Paecilomyces lilac - inum .
- Paecilomyces lilacium dextranase (available from Novo
- Nordisk A/S has a pH optimum at about 5.5.
- a mutanase suitable for the use in an oral care composition of the invention may be produced by filamentous fungi from the group including Trichoderma, in particular from a strain of
- Trichoderma harzianum such as Tri choderma harzianum CBS 243.71
- Penicillium in particular a strain of Penicillium funiculosum, such as Penicillium funiculosum NRRL 1768, or a strain of Penicillium lilacinum, such as Penicillium lilacinum NRRL 896.
- An oral care composition of the invention may suitably have incorporated an amount of dextranase and mutanase equivalent to an enzyme activity, calculated as enzyme activity units in the final oral care product, in the range from 0.001 KDU to 1000 KDU/ml, preferably from 0.01 KDU/ml to 500 KDU/ml, espe ⁇ cially from 0.1 KDU/ml to 100 KDU/ml, and from 0.001 MU/ml to 1000 MU/ml, preferably from 0.01 MU/ml to 500 MU/ml, especial ⁇ ly from 0.01 MU/ml to 100 MU/ml and from 0.01 MU/ml to 100 MU/ml, respectively.
- the present inventors have surprisingly found that when combining a dextranase from Paecilomyces lilacinum and a mu- tanase from Tri choderma harzianum a synergistic effect is ob ⁇ tained when hydrolysing mutan at 37°, pH 5.5 (see Example 1) .
- the dosage response curve of mutan hy ⁇ drolysis using the above mentioned enzymes shows a synergistic effect at pH 5.5 at 37°C. This is advanta ⁇ geous as a reduced amount of enzymes need to be used to remove plaque from the teeth or to prevent the formation of plaque on the teeth.
- the enzymes used are recombinant.
- the enzymes i.e. dextranase and the mutanase
- the enzymes are substantially active at temperatures between 20°C and 45°C, especially around 37°C, as the temperature pre ⁇ vailing in the human mouth lies within said interval.
- substantially active means in the context of the present invention that the enzyme in question has a relative activity above 70%, in particular above 80%, especially above 90% of the activity at the temperature optimum. It is also contemplated according to the invention to in ⁇ clude other enzyme activities in the oral care compositions of the invention.
- Contemplated enzymes, beside dextranase and mu ⁇ tanase, may be from the group including proteases, such as pa- pain, endoglucosidases, lipases, amylase and mixtures thereof.
- the invention also relates to oral care products comprising an oral care composition of the invention.
- the oral care prod- uct may have any suitable physical form (i.e. powder, paste, gel, liquid, ointment, tablet etc.) .
- An "oral care product” can be defined as a product which can be used for maintaining or improving the oral hygiene in the mouth of humans and ani ⁇ mals, by preventing formation of dental plaque, removing den- tal plaque, preventing and/or treating dental diseases etc.
- oral care products do also encompass products for cleaning dentures, ar ⁇ tificial teeth and the like.
- oral care products include toothpaste, dental cream, gel or tooth powder, odontic, mouth washes, pre- or post brushing rinse formulations, chewing gum, lozenges, and candy.
- Toothpastes and tooth gels typically include abrasive pol ⁇ ishing materials, foaming agents, flavouring agents, humec- tants, binders, thickeners, sweetening agents, whiten ⁇ ing/bleaching/ stain removing agents, water, and optionally enzymes .
- Mouth washes including plaque removing liquids, typically comprise a water/alcohol solution, flavour, humectant, sweet- ener, foaming agent, colorant, and optionally enzymes.
- Abrasive polishing material might also be incorporated into the dentifrice product of the invention.
- said abrasive polishing material includes alumina and hydrates thereof, such as alpha alumina trihydrate, magnesium trisilicate, magnesium carbonate, kaolin, aluminosilicates, such as calcined aluminum silicate and aluminum silicate, cal ⁇ cium carbonate, zirconium silicate, and also powdered plas- tics, such as polyvinyl chloride, polyamides, polymethyl meth ⁇ acrylate, polystyrene, phenol-formaldehyde resins, melamine- formaldehyde resins, urea-formaldehyde resins, epoxy resins, powdered polyethylene, silica xerogels, hydrogels and aerogels and the like .
- alumina and hydrates thereof such as alpha alumina trihydrate, magnesium trisilicate, magnesium carbonate, kaolin, aluminosi
- abrasive agents are calcium pyrophosphate, water-insoluble alkali metaphosphates, dical- cium phosphate and/or its dihydrate, dicalcium orthophosphate, tricalcium phosphate, particulate hydroxyapatite and the like. It is also possible to employ mixtures of these substances.
- the abrasive product may be present in from 0 to 70% by weight, preferably from 1% to 70%.
- the abrasive material content typically lies in the range of from 10% to 70% by weight of the final toothpaste product .
- Humectants are employed to prevent loss of water from e . g. toothpastes.
- Suitable humectants for use in oral care products according to the invention include the following compounds and mixtures thereof: glycerol, polyol, sorbitol, polyethylene glycols (PEG) , propylene glycol, 1,3-propanediol, 1,4- butanediol, hydrogenated partially hydrolysed polysaccharides and the like.
- Humectants are in general present in from 0% to 80%, preferably 5 to 70% by weight in toothpaste.
- Silica, starch, tragacanth gum, xanthan gum, extracts of Irish moss, alginates, pectin, cellulose derivatives, such as hydroxyethyl cellulose, sodium carboxymethyl cellulose and hy ⁇ droxypropyl cellulose, polyacrylic acid and its salts, poly ⁇ vinylpyrrolidone, can be mentioned as examples of suitable thickeners and binders, which helps stabilizing the dentifrice product .
- Thickeners may be present in toothpaste creams and gels in an amount of from 0.1 to 20% by weight, and binders to the extent of from 0.01 to 10% by weight of the final product.
- anionic, cationic, non-ionic, ampho ⁇ teric and/or zwitterionic surfactants can be used. These may be present at levels of from 0% to 15%, preferably from 0.1 to 13%, more preferably from 0.25 to 10% by weight of the final product .
- Surfactants are only suitable to the extent that they do not exert an inactivation effect on the present protease.
- Sur ⁇ factants include fatty alcohol sulphates, salts of sulphonated mono-glycerides or fatty acids having 10 to 20 carbon atoms, fatty acid-albumen condensation products, salts of fatty acids amides and taurines and/or salts of fatty acid esters of isethionic acid.
- Suitable sweeteners include saccharin.
- Flavours such as spearmint
- Whitening/bleaching agents include H 2 0 2 and may be added in amounts less that 5%, preferably from 0.25 to 4%, calculated on the basis of the weight of the final product. Water is usually added in an amount giving e . g. toothpaste a flowable form.
- water-soluble anti-bacterial agents such as chlor- hexidine digluconate, hexetidine, alexidine, quaternary ammo ⁇ nium anti-bacterial compounds and water-soluble sources of certain metal ions such as zinc, copper, silver and stannous ( e . g. zinc, copper and stannous chloride, and silver nitrate) may also be included.
- certain metal ions such as zinc, copper, silver and stannous ( e . g. zinc, copper and stannous chloride, and silver nitrate) may also be included.
- Also contemplated according to the invention is the addi ⁇ tion of compounds which can be used as fluoride source, dyes/colorants, preservatives, vitamins, pH-adjusting agents, anti-caries agents, desensitizing agents etc.
- Enzymes are biological catalysts of chemical reactions in living sys- tems. Enzymes combine with the substrates on which they act forming an intermediate enzyme-substrate complex. This complex is then converted to a reaction product and a liberated enzyme which continue its specific enzymatic function.
- Enzymes provide several benefits when used for cleansing of the oral cavity.
- Proteases break down salivary proteins, which are adsorbed onto the tooth surface and form the pellicle, the first layer of resulting plaque.
- Proteases along with lipases destroy bacteria by lysing proteins and lipids which form the structural components of bacterial cell walls and membranes.
- Dextranase breaks down the organic skeletal structure produced by bacteria that forms a matrix for bacterial adhesion.
- Prote- ases and amylases not only prevents plaque formation, but also prevents the development of calculus by breaking-up the carbohydrate-protein complex that binds calcium, preventing mineralization.
- a toothpaste produced from an oral care composition of the invention may typically comprise the following ingredients :
- the oral care product is toothpaste having a pH in the range from 4.0 to about below 6.0 comprising a) 10% to 70% Abrasive material b) 0 to 80% Humectant c) 0.1 to 20% Thickener d) 0.01 to 10% Binder e) 0.1% to 5% Sweetener f) 0 to 15% Foaming agent g) 0 to 5% Whitener i) 0.0001% to 20% Enzymes.
- Said enzymes referred to under i) include dextranase and mutanase described above, and optionally other types of en ⁇ zymes mentioned above known to be used in toothpastes and the like.
- the oral care product is a toothpaste have any of the composition encompassed by US patent no. 5,320,830 (from Proctor & Gamble) .
- a mouth wash produced from an oral care composition of the invention (in weight % of the final mouth wash composition) may typically comprise the following ingredients: 0-20% Humectant 0-2% Surfactant 0-5% Enzymes 0-20% Ethanol 0-2% Other ingredients ( e . g. flavour, sweetener active ingredients such as fluorides) . 0-70% Water
- the mouth wash composition may be buffered with an appro ⁇ priate buffer to pH 4 to below 6.
- the mouth wash may be in none-diluted form (i.e. must be diluted before use) .
- Said enzymes referred include a dextranase and mutanase de ⁇ scribed above, and optionally other types of enzymes mentioned above known to be used in mouth washes .
- the invention relates to the use of the composition of the invention or an oral care product of the invention for preventing the formation of plaque or for remov ⁇ ing dental plaque.
- Using a product of the invention typically involves apply- ing a safe and effective amount of said product to the oral cavity. These amounts ( e . g. from 0.3 to about 2 grams) , if it is a toothpaste or toothgel, is kept in the mount from about 15 seconds to about 12 hours.
- the oral care composition and products of the present in ⁇ vention can be made using methods which are common in the oral product area.
- Hydroxyapatite disks are prepared by compressing 250 mg of hydroxyapatite in a disk die at about 5,900 kg (13,000 lbs) of pressure for 5 minutes. The disks are then sintered at 600°C for 4 hours and finally hydrated with sterile de-ionised wa ⁇ ter.
- HA disks are sterilised at 180°C for two hours, hydrated with the sterilised de-ionised water and placed in a lid of Nunc tube (10 ml volume) .
- Mutan is prepared by growing Streptococcus mutans CBS 350.71 at pH 6.5, 37°C (kept constant), and with an aeration rate of 75 rpm in a medium comprised of the following components: NZ-Case 6.5 g/liter
- sucrose is added to a final concentration of 60 g/liter to induce glucosyltransferase .
- the total fermenta ⁇ tion time is 75 hours.
- the supernatant from the fermentation is centrifuged and filtered (sterile) .
- Sucrose is then added to the supernatant to a final concentration of 5 % (pH is ad ⁇ justed to pH 7.0 with acetic acid) and the solution is stirred overnight at 37°C.
- the solution is filtered and the insoluble mutan is harvested on propex and washed extensively with deionized water containing 1% sodium benzoate, pH 5 (adjusted with acetic acid) . Finally, the insoluble mutan is lyophilized and ground.
- KDU dextranase activity
- MU Mutanase Unit
- Streptococcus mutans OMZ 176 (CBS 350.71) is inoculated in a glass tube (22 mm diameter x 150 mm height) containing 10 ml Todd Hewitt Broth with 2% sucrose and the tube is allowed to stand overnight at 37°C. The broth is discarded and adhered mutan and Streptococcus mu tans cells on glass wall are washed twice with 10 ml of 0.85% NaCl solution.
- the method used for assessing the plaque removal effect is based on the method described by Kao in JP2250816.
- the hydroxyapatite disks are coated with a biofilm comprising three strain of oral micro-organisms (Streprtoc ⁇ ccus mutans , Actinomyces viscosus and Fusobacte ⁇ rium nuclea tum) .
- Erythrosin B in PBS is used to stain plaque present on the hydroxyapatite disks red.
- the intensity of the red color i.e. a*
- the max. a* value is 60. Values below that indicate a less intensive red color ( i . e . less plaque present) . If the a* value is determined to zero no red color is present (i.e. no plaque) .
- 50 mM Britton-Robinson buffer solutions having the pH ad ⁇ justed to 5.5 were also prepared. 250 ml of each of the above mentioned enzyme solutions and 500 ml of buffer solution (pH 5.5) were mixed in a microcen- trifuge tube. Immediately thereafter 250 ml of Mutan suspen ⁇ sion was added, incubated at 37°C in a shaker at the maximum speed. After exactly 30 and 60 minutes, 250 ml of a 0.5 N HCI was added to terminate the enzymatic reaction. A 0 time control was prepared by adding a 0.5 N HCI before addition of a sub ⁇ strate suspension. Each of the reaction mixtures were sub ⁇ jected to centrifugation. The solubilized sugar, in the ob- tained supernatant, was determined according to the anthrone reaction method (J.H. Roe, (1955), J. Biol. Chem. 212, p.
- Mutanase solution (0.4, 2.0 and 4.0 MU/ml)
- a mixed enzyme solution (0.4, 2.0 and 4.0 KDU and 0.4, 2.0 and 4.0 MU/ml, respectively) .
- Dextranase solution (4 KDU/ml)
- Mutanase solution (4 MU/ml)
- a mixed enzyme solution (4 KDU and 4 MU/ml)
- 50 mM Britton-Robinson buffer solutions having the pH adjusted to 5.0, 5.5, 6.0, 6.5, 7.0, 7.5 and 8.0 were also prepared.
- the disks were r nsed briefly with PBS and then incubated in a 1 ml 0.1 % Erythrosin B (Sigma) in PBS for 1 minute to stains plaque present on the hydroxyapatite disks red.
- the disks were air dried overnight.
- the intensity of the red color i.e. a* was measured on a Chromameter CR-200. The higher the a* value is the more red are the hydroxyapatite disks.
- the Erythrosin B solution was removed and the disks were rinsed with PBS for a few minutes .
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Abstract
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU23810/97A AU2381097A (en) | 1996-04-16 | 1997-04-16 | Compositions for the removal of dental plaque |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK44996 | 1996-04-16 | ||
DK0449/96 | 1996-04-16 |
Publications (1)
Publication Number | Publication Date |
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WO1997038670A1 true WO1997038670A1 (fr) | 1997-10-23 |
Family
ID=8093685
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/DK1997/000163 WO1997038670A1 (fr) | 1996-04-16 | 1997-04-16 | Compositions permettant l'elimination de la plaque dentaire |
Country Status (2)
Country | Link |
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AU (1) | AU2381097A (fr) |
WO (1) | WO1997038670A1 (fr) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2327345B (en) * | 1997-07-18 | 1999-06-23 | Finnfeeds Int Ltd | Use of an enzyme for manufacturing an agent for controlling bacterial infection |
WO2004009050A1 (fr) * | 2002-07-23 | 2004-01-29 | Colgate-Palmolive Company | Film pour rafraichir l'haleine ameliore par une enzyme |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4466954A (en) * | 1981-12-29 | 1984-08-21 | Lion Corporation | Oral composition |
US5320830A (en) * | 1992-12-30 | 1994-06-14 | The Procter & Gamble Company | Oral compositions |
-
1997
- 1997-04-16 WO PCT/DK1997/000163 patent/WO1997038670A1/fr active Application Filing
- 1997-04-16 AU AU23810/97A patent/AU2381097A/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4466954A (en) * | 1981-12-29 | 1984-08-21 | Lion Corporation | Oral composition |
US5320830A (en) * | 1992-12-30 | 1994-06-14 | The Procter & Gamble Company | Oral compositions |
Non-Patent Citations (3)
Title |
---|
DIALOG INFORMATION SERVICES, File 155, MEDLINE, Dialog Accession No. 02909591, Medline Accession No. 77150500, BUDTZ-JORGENSEN E. et al., "Enzymes as Denture Cleansers"; & SCAND. J. DENT. RES., (Denmark), Mar. 1977, 85(3), P. 209-15. * |
DIALOG INFORMATION SERVICES, File 351, Dialog Accession No. 004561593, WPI Accession No. 86-064937/198610, LION CORP, "Tooth Paste Compsn. - Comprising Reformed Aluminium Hydroxide and Enzyme(s)"; & JP,A,61 015 827, 23-01-1986. * |
FILE WPI, Derwent Accession No. 72-56480T, KOJIN CO. LTD., "Extranase Prodn.-Used in Prevention of Caries"; & JP,B,47 034 148, DW7235. * |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2327345B (en) * | 1997-07-18 | 1999-06-23 | Finnfeeds Int Ltd | Use of an enzyme for manufacturing an agent for controlling bacterial infection |
WO2004009050A1 (fr) * | 2002-07-23 | 2004-01-29 | Colgate-Palmolive Company | Film pour rafraichir l'haleine ameliore par une enzyme |
CN100421639C (zh) * | 2002-07-23 | 2008-10-01 | 高露洁-棕榄公司 | 酶增强的气味清新薄膜 |
AU2003252046B2 (en) * | 2002-07-23 | 2009-08-13 | Colgate-Palmolive Company | Enzyme enhanced breath freshening film |
Also Published As
Publication number | Publication date |
---|---|
AU2381097A (en) | 1997-11-07 |
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