[go: up one dir, main page]

WO1997038670A1 - Compositions permettant l'elimination de la plaque dentaire - Google Patents

Compositions permettant l'elimination de la plaque dentaire Download PDF

Info

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
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/DK1997/000163
Other languages
English (en)
Inventor
Rie Tsuchiya
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novo Nordisk AS
Original Assignee
Novo Nordisk AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Novo Nordisk AS filed Critical Novo Nordisk AS
Priority to AU23810/97A priority Critical patent/AU2381097A/en
Publication of WO1997038670A1 publication Critical patent/WO1997038670A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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 .

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Birds (AREA)
  • Cosmetics (AREA)

Abstract

Cette invention a trait à des compositions ainsi qu'à des produits d'hygiène bucco-dentaire comportant une dextranase ainsi qu'une mutanase et, éventuellement, d'autres enzymes.
PCT/DK1997/000163 1996-04-16 1997-04-16 Compositions permettant l'elimination de la plaque dentaire Ceased WO1997038670A1 (fr)

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
DK0449/96 1996-04-16
DK44996 1996-04-16

Publications (1)

Publication Number Publication Date
WO1997038670A1 true WO1997038670A1 (fr) 1997-10-23

Family

ID=8093685

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DK1997/000163 Ceased WO1997038670A1 (fr) 1996-04-16 1997-04-16 Compositions permettant l'elimination de la plaque dentaire

Country Status (2)

Country Link
AU (1) AU2381097A (fr)
WO (1) WO1997038670A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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

Patent Citations (2)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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

Similar Documents

Publication Publication Date Title
EP0907349B1 (fr) Compositions permettant l'elimination de la plaque dentaire
CN101703453B (zh) 具有增强的稳定性的含酶口腔组合物
RU2300366C2 (ru) Содержащая ферменты двухкомпонентная композиция против зубного налета
US6207149B1 (en) Starch binding domains (SBDs) for oral care products
JPH09301840A (ja) 口腔用組成物
EP1011700B1 (fr) Composition d'hygiene bucco-dentaire renfermant une bacillus pullulanase et une dextranase
WO1998016191A1 (fr) Domaine de liaison a la cellulose pour produits de soins bucco-dentaires
US6413501B2 (en) Plaque-inhibiting oral compositions
EP1536761B1 (fr) Composition dentaire a composant double contenant une enzyme
AU734737B2 (en) Plaque-inhibiting oral compositions
WO1997038670A1 (fr) Compositions permettant l'elimination de la plaque dentaire
DE69807712T2 (de) Zusammensetzung zur mundhygiene, die eine bakterielle pullulanase und dextranase enthält

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TM TR TT UA UG US UZ VN AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH KE LS MW SD SZ UG AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

NENP Non-entry into the national phase

Ref country code: JP

Ref document number: 97536662

Format of ref document f/p: F

NENP Non-entry into the national phase

Ref country code: CA

122 Ep: pct application non-entry in european phase