AU677202B2 - Prophylactic and therapeutical preparation against caries - Google Patents

Prophylactic and therapeutical preparation against caries Download PDF

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AU677202B2
AU677202B2 AU43083/93A AU4308393A AU677202B2 AU 677202 B2 AU677202 B2 AU 677202B2 AU 43083/93 A AU43083/93 A AU 43083/93A AU 4308393 A AU4308393 A AU 4308393A AU 677202 B2 AU677202 B2 AU 677202B2
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preparation according
proportion
calcium
acid
phosphate
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Wolfgang Wiedemann
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/66Phosphorus compounds
    • A61K31/661Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/06Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/24Phosphorous; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/12Drugs for disorders of the metabolism for electrolyte homeostasis
    • A61P3/14Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
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  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Inorganic Chemistry (AREA)
  • Hematology (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Endocrinology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Birds (AREA)
  • Rheumatology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Confectionery (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Dental Preparations (AREA)
  • Orthopedics, Nursing, And Contraception (AREA)

Abstract

A prophylactic and therapeutical preparation against caries designed as a chewing gum, a candy for chewing or sucking, tooth paste, mouth wash or spray and the like, contains a proton donor as well as dissolved or easily soluble calcium and dissolved or easily soluble phosphate.

Description

OPI DATE 24/01/94 APPLN. ID 43083/93 11111 11111111IIIHII 111111 AOJP DATE 14/04/94 PCT NUMBER PCT/DE93/00579 LIIII II 'l AU9343083 (51) Internationale Patenikiassilnkatlon A61K 7/16, 7/26 00I Iternationale Verif en lchungsnummer: WVO 94/00101 At (43) Intcrnallonales Verbl'fcntlichungsdaturn: 6. J.uar 1994 (06.01.94) (21) Internationales Aktonzelchen: (22) Internationales Anneldedatum: PCT DE93 00579 30. Juni 1993 (10.06.93) .41it internatioinalem Reclwrchenlwriclht.
677202 Prioritiitsdatcn: P 42 21054.2 30. Juni 1992 (30.06.92) (7 1 X72) Anmelder und Erfinder: WI EDEMANN, Wolfgang IDE 'lDi; Am Ziegelbaum S1, D-97204 lWichberg (DE).
(74) An~salt: POHN ER, Wilfricd; Postfach 6323, Kaiserstr. 27, D-97013 W~rzburg (DE).
(81) Bestimmungsslaafen: AU, BJR, CA, Fl. JP, KP. KR. NO, US, curop~lisches Patent (AT, BE, CH. DE, DK, ES, FR, GBl, GR, 113, IT, LU, MC, NL, PT, SE).
(54)1Ti1le: PROPHYLACTIC AND THERAPEUTICAL PREPARATION AGAINST CARI ES (54) Bezelchnung: PRAPARAT ZUR PROPHYLAKTISCHEN UND THERAPEUTISCHEN BEHANDLUNG VON KA- RI ES 1M.l .1 Intraorole DEM-REM liabtitte S, 24 $turi.n lnlti~o,.lt pZytkus) Io Ina~ I~tI MW It,.,IMi i4l.* 03134 llso its-0 244 ft Ml U tli..*flI..dt Ii IN iii MW 1,0 fi N MW dam 01606 a"4 IA I06"M i~ a il Wad a-tt 02,. S 5 11 tlif.,1r REM L6WIV5Io.,4o 1#3) RE. (01)N S. U Ml NI (57) Abstract A prophylactic and therapeutical preparation against caries designed as a chewing gum, a candy for chewing or sucking, tooth paste, mouth wash or spray and the like, contains a proton donor as well as dissolved or easily soluble calcium and dissolved or easily soluble phosphate.
(57) Zusammenfassung Vorgeschlagen wird ein Priiparat for die prophylaktische und therapeutische Ilehandlung von Karies, in Form ciner Kaumasse, Kaubonbons, Lutschbonbons, Zahnpasta, Mundwasser, Mundspray und dgl., wobei emn Protonenspender sowie gel~stes oder leicht I~sliches Calzium und gelbstes oder leicht ii~sliches; Phosphat vorhanden ist.
Proxhiactic and Therapeutical Preparation Against Caries T1he invention concerns a preparation for theA4eh=4*.and therapeutic treatment of caries, in the formn of a chcwablo mass, chewable sweets, sucking sweets, toothpaste, mouth wash, mouth spray and similar.
With caries, poilit-by-point dostruction of thre tooth enaincl and, fromi time to time, also of the dentine underneath, causes lesions. As a preparative mecasure to save the tooth, the damaged region of the dental cnaniel and the dentine is first removed with the aid of a drill so that a cavity is formed. Afler disinfecting, the cxavity is filled through the insertion of certain materials in the forin of amnalgamn, plastic, cemient, gold or similar in order to prevent dirt, bacteria fromn entering. Finally, the surface of the filling material and espcially the surface of the transition zone is polished to prevent the rcoccurrence of caries.
It is to be seen as disadvantageous that the prior art method is costly and under circumstances requires more thani one visit to the physiciain.
It is the obct of this invenition to provide a preparation for remineralisation, the use of which creates optimnum conditions -2in the oral cavity and/or directly at the tooth.
This object is solved therein that it is proposed to provide a proton donor as well as dissolved or easily soluble calcium and dissolved or easily soluble phosphate. The preparation is uted orally, e.g. in the form of a sucking or chiewable swc%;t or a chiewable mass. Toothpaste, miouth wash, mouth spray or other preparations for daily dental and oral hygiene, can also be viewed as vehiclcs.
The invention is based on the recognition that the process causing carics is reversible. Results from both experimental tests as well as a mathematical diiffu sion-reaction model show that the non-stationary marg~inal conditions for the mineral exchange processes at the teeth are ospecially important: only adequately varying concentrations of dissolved mineral (essentially calcium and phosphate) and the pH- value and inactive ingredients such as, fluoride in the oral cavity environment, whichi rinse the lesion, facilitate a complcte and deep remineralisation of the lesion. The samec processes play an important role in the prophylactic, saturation of the hard dental substance with rninerals.
The mineralisation process described is largely defined by physicochemical values such as the deposition rate of mineral from the dissolved phase, the saturation concentration at the respective pl value, or the -3dilfusion constants of' the different diss6lved components, These parameters and the substrate surface, i.q. the active surface in the enatnel, infinonce the quantity, type and structute of the deposited mineral, I'lese processcs viewed initially in vitro also function in vivo, The exploitation o~f this recognition in ordcr to develop a caries prophy.'actic or therapy is largely defined by the possibility of creating the optimm conditions in the oral cavity or directly at tho tooth. This also includes the creation of optimum conditions for remineral isat ion, which lie in the acidic range. Tlhe addition of a proton donor serves to generate (initially from a neutral condition) a low p1-i vaue. Only thcn arc the calcium and phosphate bonds dissociated.
A
For a sucking sweet, sugar or sugar substitutes such as xylito, sotbit or isomalt can be used the as base mass. Further possibilities consist of sugar substitutes and/or gelaline and/or 'gumn arabic and/or chewable mass.
In tho formulation of a recipe ffbr an application, the bul~r action of thec residual phosphate and that of the saliva must be considered. An imiportanit point of view for the comnposition is also the saliva clearance, i.e. the quantity of introduced agents which aire diluted and swallowved via thc saliva. This proportion is greatly influenced by the form of application (sticking sweet, chewable sweet toothpaste In the caso of an initial p11 value of p11i-4-4.5, which is required for a controlled reineralisalion, one part of the phosphate is provided as H-2P04 ion, i.e.
only simply dissociated in solution. The undissocialed protons, fixed to the phosphate, must be additionally addcd. This can be done, in the form of citrate or another acid used in confectionery making for aroniatising lactic acid, mnalic acid, tartaric acid, general fruil acid).
The use of calciwnm chloride ais a calcium donor is also conceivable, To delay the clearance of the substances deriving firom the device and therefore to control the concentration profile.s, substiince!; can also be added to the devices, especially the toothpaste, the miouth wash and the mouth spray, 'which, on the one hand, physically bind calcium and/or phosphate in large quantities, on the other hand, are themnselves adsorbed on the tooth surface and/or oral cavity mucous mombrane. Such substances are mostly of organic natuire and bipolar and are used as fluoride carriers in caries therapy, such as amnine fluoride. Substances firom tho class of the chiorhexidine digluconate and the quarternary anmmoniumn bases, are also used for shiiar purposes, e.g. to prolong the disinfiecting effect with chiorhexidine and bcnzoxonium chloride).
But also additions of higher viscosqity which are deposited on the tooth and ihe mucous membrane and which can contain adsorbed calcium and phosphate adsorbed, can be considered 1o delay the clearance. Nature forms such substances, in the dental plaque i the form of extracclilular polysaccha rides. Thierefore, such an addition can, be a substance from the class of the polyglucans.
In an acidic environment, Ca-P04 often does not precipitate in a solid form or in thc most favourable energctic form, hydroxylapatito. Therefore, escort substances are to be added to) the'formulation, which act as catalysis for the formation of solid hydroxylnpalile and to avoid fractional deposition. For example, fluoride is known as such a substAtice.
The explanations show that thore are different formulations for the composition of the proparation depondit'g on the kind of application: a) For sucking sweets or chewable swedts with an average retention time of 5-8 rninutes in the mouth, the mechanism described above, while considoring salivation, can be realised through the folowing composition.
Tlhe constant loss of mineral componenits through swallowing of the solutions is taken into account: Per kg of sweet mnass, 200 to 800 niM, prefbrably 300 to 600 niM, especially 400 to 500 aiM of calcium or calcium compounds must be addcd, which corresponds to more or less 0,9 to 3.6 weight per cent, 1.35 to 2.7 weight per cent and 1 .8 to 2.25 weight per cent respectively of calcium (compounds).
Because of the existing high phosphate content (content of phosphate ions) of thc saliva, the supply of phosphate (ions) through the described device can be linifted to between 50 and 400 niM, especially 100 to 300 mnM. Expressed i n weight per cent: 0.4 7 to 3.73 or 0.94 to 2.82 per cent P04.
One part of the protons required for aciaifying is buffecred by phosphate (ions). For this reason and through the incomplete dissociation of the different fruit acids, it is lost for the acidification of the oral cavity' environment. The addition of acid governed by these conditions, Required to acidify the oral cavity are 290 mnM H per kg of sweet Mass (this value is based on measurements taken in the mouth).
Taking into account the aforementioned conditions, if a calcium fruit acid salt is used as a calcium donor, a fruit acid content of 400 to 1 500 millival is required. Converted to the tribasic critic acids, this mcans, depending on the degree of dissociation, a content of approx. 2,8 to I11 weight per cent of citrate, To catalyse the solid disposition of hydroxylapatile, the sweet should also contain 0.7 to 2.4 niM of fluoride/kg of sweet.
b) For an application as toothpaste, considering the dilution effect through the saliva and its buffer capacity, a formulation in the following limits must be considered: 160 to 660 mM Ca, preferably 240 to 500 mM, especially 320 to 440 mM Ca and 40 to 330 mM, preferably 80 to 250 mM P04. Of acid, one requires between 300 and 1200 millival. All data applies to 1 kg of toothpastc.
Onc part. of the calcium and phosphate dan, as described, be given in an adsorptive carrier.
The FApplication form as toothpaste has the great advantage that, as also described belowv, it is digiributed evenly in the mouth and creates vory homogenous conditions. The carrier is dspecially important because of the relatively short retention time of the actual toothpaste in the mouth, c) The concentrations in the mouth wash are lower than in the ease of the o)ther two formulations bccause of the relative large quantities of liqufid that are taken up during rinsing. To create the most favourable conditions possible in the oral cavity for hardening the tooth enamel, a mouth rinso solution can be composed as follows: to 22 mM Ca, preferably 8 to 16 mnM, especially 10 to 15 mM Ca and I to 10, preferably 3 to 8 m)M P04 and 10 to 14 millival of acid/kg of niouth wash. These values rofer to a. ready-for-use solution with nil/application. The formulations in exam'ples h and c are also to be augmiented with low doses of fluoride. During a certalin. time all of these Ibrmnulations create an environment in the oral cavity in which the tooth enamel is impregnated with dissolved miinerals from a saturated solution at a lowered pH valute. T1hrough the use'of the acidic sweet or the washing out of the calcium and phosphate adsorp'Iive carrier in toothpastes or mouth washes, there is ani increase in the p]1I value on the surface and a concentration gradient between the surface of the enamel and its interior.
This causes a diffusion eirent of protons, calcium and phosphate ions in the direction of the exterior environment. Because of the greater mobility of the protons compared with the calcium1 and phosphate ions, there is a faster incrcase in the pH value inside the enamecl. This forces the calciumn and phosphate ions under the enamel surface to precipitate and they are deposited as a solid material.
Figure I shows a niensut-enient of the mass (---mineral) growth in a porous hydroxiapatite sample. Such samples behave like tooth enamel as concerns demlineralisation and rcmincrqlisation, and as is known tooth -9enamel consists primarily of'this material, Thle sainples were worn in the mouth on a dental plate and inserted three timecs daily during oral hygiene minute,,) in a solution with pH--4.5 which was saturated with calcium and phosphate.
Asa control, in a. second stage, the same sample was placed in distilled water and in a third experimental round again in the acidic calcium phosphate solution. The poin~ts on the diagram show the weight of the sample atl the beginning of the test, after the first day with the acidic calcium phosphate solution, after one day with distilled water and then Outr a fit-thor day with aii acidic calcium phosphate solution.
Obvious is a mineral increase of' 1 .4 nig after the two experimental stages with reirteralisation solution, while the experimental stage with distilled water resulted in a mineral loss of I mg, In Ili,) case of sucking a sweet with, 0.44 mole/kg Ca and 0.27 molc/kg P04, with a acid content of 3.5% citric acid in the buccal cavity, thc result is the temporal pH profile repfesented in Figure 2. Afer introduction of the sweet into the oral cAvity, the pH value in the saliva falls within I minute to p11 4. Due to the cuboid dosigh of the sweet, the disintegration of its surface is temporally essentially constant, so that per time the same quantity of acid always detaches. Tlherefore, a plateau 410forms at about p11 4. After dissolution or removal of the sweet, the pl value in the saliva of the molar area again increa9ses due to saliva clearance within 3.2 minutes, Corrcspoiiding curves with a higher p)1I plateau ctnr be achieved with other acid contents,
ABSTRACT
Preparation for the Prophylaetic and Therapeutic Treatmenut of Caries Proposed is a preparation for the proph~'lacfic and therapeutic treatinont of carics, in the form of a ohee'able inass, chewable sweets, sucking sweets, toothpaste, mouth wash, miouth spray and similar, whereby a proton donor and dissolvod or easily soluble calcium wid dissolved or easily soluble phosphiato are provided.
Figure I

Claims (16)

  1. 2. Preparation according to claim 1, wherein the base mass of the preparation is selected from the group consisting of sugar, sugar substitute, gelatine, gum arabic, chewing mass and mixtures thereof.
  2. 3. Preparation according to claim 1 or 2, wherein the proton donor is an organic acid.
  3. 4. Preparation according to claim 3, wherein the organic acid is an acid used to aromiatise confectionery. Preparation according to claim 4, wherein the acid used to aromatise confectionary is selected from the group consisting of citric acid, lactic acid, fruit acid, tartaric acid and mixtures thereof. 20 6. Preparation according to any one of claims 1 to 5, wherein the calcium compound is a calcium fruit acid salt.
  4. 7. Preparation according to any one of claims 1 to 6, wherein in a solid state the proportion of calcium is 0.9 to 3.6 weight per cent, and that of the phosphate is 0.47 to too. 3.73 weight percent, and a quantity of 400 to 1500 millival fruit acid per kilogram of 25 solid mass. Preparation according to claimi 7, wherein the proportion of calcium is 1.35 to 2.7 weight per cent. 2 Preparation according to claim 8, wherein the proportion of calcium is 1.8 to 2.2 weight per cent.
  5. 10. Preparation according to any one of claims 7 to 9, wherein the proportion of phosphate is 0.94 to 2.82 weight percent.
  6. 11. Preparation according to any one of claims 1 to 10, wherein with a toothpaste there is a proportion of 160 to 600 mM calcium compounds per kilogram and in the case of phosphate a proportion of 40 to 330 mM/kg and the acid proportion is 300 (o 1200 millival/kg of toothpaste.
  7. 12. Preparation according to claim 11, wherein there is a proportion of 240 to 500 mM/kg calcium compounds.
  8. 13. Preparation according to claim 12, wvherein there is a proportion of 320 to 400 mM/kg calcium compounds. ,N:~hbaajQO62i :JVR 13
  9. 14. Preparation according to any one of claims 11 to 13, wherein there is a proportion of 80 to 250 mM/kg phosphate. Preparation according to any one of claims 1 to 14, wherein with mouth wash the proportion of the calcium is 5 to 22 mM/kg the proportion of the phosphate is 1 to mM/kg and the proportion of acid is 10 to 40 millival/kg.
  10. 16. Preparation according to claim 15, wherein the proportion of calcium is 10 to mM.
  11. 17. Preparation according to claim 15 or claim 16, wherein the proportion of phosphate is 3 to 8 mM.
  12. 18. Preparation according to any one of claims 1 to 17, wherein the content of a substance that inhibits fractional precipitation, is in a concentration of 0.7 to 2.4 mM/kg.
  13. 19. Preparation according to claim 18, wherein fluoride is in a concentration of 0.7 to 2.4 mM/kg. Preparation according to any one of claims 1 to 19, wherein a calcium adsorptive substance or a phosphate adsorptive substance or both is -dded.
  14. 21. Preparation according to claim 20, wherein the adsorptive substance is a polyglucan.
  15. 22. Preparation according to claim 20, wherein the adsorptive substance is a mucin,
  16. 23. Preparation according to claim 20, wherein the adsorptive substance is bipolar. Dated 16 September, 1996 Wolfgang Wiedemann 5 0 *o Patent Attorneys for the Applicant/Nominated Person SPRUSON FERGUSON t11**1 [N:\libaa100621:jvr
AU43083/93A 1992-06-30 1993-06-30 Prophylactic and therapeutical preparation against caries Ceased AU677202B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE4221054 1992-06-30
DE4221054A DE4221054A1 (en) 1992-06-30 1992-06-30 Preparation for the prophylactic and therapeutic treatment of caries and method for producing the same
PCT/DE1993/000579 WO1994000101A1 (en) 1992-06-30 1993-06-30 Prophylactic and therapeutical preparation against caries

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Cited By (1)

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AU2004281513B2 (en) * 2003-10-17 2009-06-25 Mederer Suesswarenvertriebs Gmbh Chewable compound for the remineralisation of tooth enamel

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US5658554A (en) * 1995-06-01 1997-08-19 Colgate-Palmolive Company Mouth moistener for the relief of dry mouth condition
DE19629167C2 (en) * 1996-07-19 2000-05-04 Einhorn Apotheke Dr Guenther H Solid oral anti-cariogenic composition in the form of a lozenge for cleaning the oral cavity and teeth
US5833954A (en) * 1996-08-20 1998-11-10 American Dental Association Health Foundation Anti-carious chewing gums, candies, gels, toothpastes and dentifrices
US6491900B2 (en) * 1996-08-20 2002-12-10 American Dental Association Health Foundation Anti-carious candies and confections
JP5633998B2 (en) * 2006-09-27 2014-12-03 三栄源エフ・エフ・アイ株式会社 Tooth remineralization promoter and oral or oral composition containing the same
MA50077A (en) 2017-09-08 2020-07-15 Amgen Inc KRAS G12C INHIBITORS AND THEIR PROCEDURES FOR USE
CA3098574A1 (en) 2018-05-04 2019-11-07 Amgen Inc. Kras g12c inhibitors and methods of using the same
WO2021091967A1 (en) 2019-11-04 2021-05-14 Revolution Medicines, Inc. Ras inhibitors
US20210139517A1 (en) 2019-11-08 2021-05-13 Revolution Medicines, Inc. Bicyclic heteroaryl compounds and uses thereof

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US4080440A (en) * 1974-12-13 1978-03-21 The Procter & Gamble Company Method for remineralizing tooth enamel
EP0091611A1 (en) * 1982-04-08 1983-10-19 Winfried Kruppa Anti-caries chewing gum
EP0344701A2 (en) * 1988-06-01 1989-12-06 The Procter & Gamble Company Oral compositions

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IE42129B1 (en) * 1974-10-10 1980-06-04 Procter & Gamble Compositions for remineralizing tooth enamel
NO158361C (en) * 1981-07-03 1988-08-31 Intradal Nv DENTAL CARE WITH ANTICARIES EFFECT.
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4080440A (en) * 1974-12-13 1978-03-21 The Procter & Gamble Company Method for remineralizing tooth enamel
EP0091611A1 (en) * 1982-04-08 1983-10-19 Winfried Kruppa Anti-caries chewing gum
EP0344701A2 (en) * 1988-06-01 1989-12-06 The Procter & Gamble Company Oral compositions

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2004281513B2 (en) * 2003-10-17 2009-06-25 Mederer Suesswarenvertriebs Gmbh Chewable compound for the remineralisation of tooth enamel

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ES2102652T3 (en) 1997-08-01
NO944831L (en) 1994-12-14
DE59304554D1 (en) 1997-01-02
AU4308393A (en) 1994-01-24
EP0648108B1 (en) 1996-11-20
GR3022582T3 (en) 1997-05-31
WO1994000101A1 (en) 1994-01-06
DE4221054A1 (en) 1994-01-05
JPH08501530A (en) 1996-02-20
NO944831D0 (en) 1994-12-14
CA2138780A1 (en) 1994-01-06
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DK0648108T3 (en) 1997-04-28
ATE145323T1 (en) 1996-12-15

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