DE3942643B4 - Oral care products - Google Patents

Abstract

Oral hygiene products containing
a) 0.01-5% by weight of a non-cationic bactericidal component whose solubility in water at 25 ° C is less than 1% by weight,
b) 0.005-4% by weight of an antibacterial enhancer activator (AVA) to increase the supply of the bactericide to the oral areas and to retain the bactericide in these areas and
c) an orally-acceptable carrier which dissolves the bactericidal component in an effective plaque-preventing amount in saliva, wherein
the oral care product is free of tartar-preventing polyphosphate compounds;
the AVA has at least one residue which attaches or attaches the AVA with the bactericide to the oral surfaces and thus increases the supply of the bactericide, and at least one residue which binds the bactericide to the AVA and thus increases the retention of the bactericide , contains;
the restoring agent provides an acidic residue selected from the group of carboxylic, phosphonic, phosphinic and sulphonic acid residues and salts thereof.

Description

The The invention relates to a bactericidal, plaque-preventing with a content of a substantially water-insoluble non-cationic bactericidal component for the prevention of dental plaque.

plaque forms on the teeth as a soft deposit during Tartar represents a hard calcified deposit. In contrast To the tartar, the plaque forms on each area of the tooth surface and especially at the gingival frontier districts; he is barely recognizable and favors Gingivitis.

For this reason, it is desirable to provide antimicrobial agents or bactericidal components in oral hygiene products which reduce dental plaque. For this purpose, cationic bactericides have often been proposed. According to U.S. Patent 4,022,880 For example, a zinc ion donating compound is mixed with a bactericide as a anticalculus component to prevent the growth of dental plaque bacteria. Numerous bactericides are described in combination with zinc compounds, including cationic compounds such as guanidines and quaternary ammonium compounds, but also non-cationic compounds such as halogenated salicylanilides and halogenated hydroxydiphenyl ethers. A non-cationic bactericidal plaque preventing halogenated hydroxydiphenyl ether, triclosan, is also used in combination with zinc citrate trihydrate in EU PS 0 161 899 described. Further disclosed Eu-PS 0 271 332 a toothpaste containing triclosan and propylene glycol as a solubilizing agent.

cationic Bactericides such as chlorhexidine, benzethonium chloride and cetylpyridinium chloride have been studied as antibacterial antiplaque agents been; however, they are generally in combination with anionic ones Components not effective. Non-cationic bactericides, however, can on the other hand with anionic components in an oral hygiene product compatible be. However, oral care products are mostly mixtures of numerous Components, where even neutral components such as humectants Behavior of such oral care products can influence.

In addition, even non-cationic bactericides have limited tooth-plating activity when compared with the commonly used other ingredients such as anticalcific polyphosphates, according to US Pat GB-PS 2,200,551 and EU Patent 0 251,591 be used. Previously unpublished work according to USSN 398,605 of August 25, 1989 showed that antiplaque efficacy can be significantly increased by employing an antibacterial enhancer activator (AVA) which increases the availability of the bactericide to the oral areas and the retention of the bactericide at these areas enhanced, allowing optimized amounts and ratios of polyphosphate and AVA.

The EP 0 220 890 A2 discloses oral care compositions containing triclosan, polyethylene glycol, flavoring oil and an orally acceptable carrier. It is generally stated that active substances against plaque and tartar may also be present without such active substances being mentioned concretely.

The DE 34 45 695 A1 relates to agents for oral-dental application against plaque and gingivitis. The agents contain a polyvinylphosphonic acid or polyvinyl phosphate. This is intended to disrupt or prevent the attachment of Actinomyces viscosus to saliva-coated hydroxyapatite sites.

In the DE 38 02 168 A1 there are described oral care compositions containing a polyphosphate salt as an essential anticalculus agent and an antiplaque effective amount of a substantially water-insoluble non-cationic antibacterial agent.

• • Copolymere aus ungesättigten Carbonsäuren oder deren Anhydriden und einen Olefin mit 2 oder mehr Kohlenstoffatomen je Molekül oder einen olefinischen Ether mit 3 oder mehr Kohlenstoffatomen je Molekül,
• • Polyolefinsulfonate,
• • Polyolefinphosphonate, deren Olefingruppen 2 oder mehr Kohlenstoffatome enthalten, und
• • Polyolefinphosphate, deren Olefingruppen 2 oder mehr Kohlenstoffatome enthalten.

The U.S. Patent 3,429,963 relates to oral care products containing polymeric polyelectrolytes. The following classes of polyelectrolytes are named:

• Copolymers of unsaturated carboxylic acids or their anhydrides and an olefin having 2 or more carbon atoms per molecule or an olefinic ether having 3 or more carbon atoms per molecule,
• • polyolefin sulfonates,
• Polyolefin phosphonates whose olefinic groups contain 2 or more carbon atoms, and
• Polyolefin phosphates whose olefinic groups contain 2 or more carbon atoms.

Of the Polyelectrolyte is intended to reduce the formation of calculus, by sequestering calcium. To prove the reduction calculus formation in vivo is described as an experiment in which a hydrolyzed copolymer of ethylene and maleic anhydride the drinking water for Rats were added and the resulting solution from the rats ad libitum Was drunk for 5 days.

The Invention has set itself the task of an oral hygiene product for Propose better prevention of dental plaque. To solve this Task an oral hygiene product according to the main claim is proposed being particular embodiments in the subclaims mentioned are.

The Oral care products according to the invention offers the advantage that a essentially insoluble in water non-cationic bactericidal component and a reinforcing activator (AVA) are provided to prevent plaque formation, the Composition of an oral carrier contains which makes it possible that this Bactericides themselves in a plaque-preventing amount in the saliva dissolves. Another advantage is that AVA is the provision and the retention of small but effective plaque preventing agents Allows amounts of the bactericidal component on the tooth and mucous membranes, which in turn creates an oral hygiene product as a further advantage which prevents the occurrence of gingivitis.

Typical examples of water-insoluble, non-cationic antibacterial or bischicides which are particularly suitable with regard to their anticalculus efficacy and tolerability or safety are the following compounds:
Halogenated diphenyl ethers such as 2 ', 4,4'-trichloro-2-hydroxydiphenyl ether (triclosan) and 2,2'-dihydroxy-5,5'-dibromo-diphenyl ether.

Further halogenated salicylanilides such as 4 ', 5-dibromo, or 3,4', 5-trichloro, or 3,4 ', 5-tribromo, or 2,3,3', 5-tetrachloro, or , 3,3,3 ', 5-tetrachloro- or 3,3,3 ', 5-tetrachlorosalicylanilides and 3,5-dibromo-3'-, or 5-n-octanoyl-3'-, or 3,5-dibromo-4'- or 3,5-dibromo-3'-trifluoromethylsalicylanilide (Fluorophene).

When benzoic are methyl, ethyl, propyl or butyl p-hydroxybenzoic acid esters suitable.

When halogenated carbanilides include 3,4,4'-trichlorocarbanilide, 3-trifluoromethyl-4-4'-dichlorocarbanilide and 3,3,4'-trichloro in question.

When phenolic compounds can the following phenols and their homologues such as mono- and polyalkylphenols and aromatic halophenols with e.g. F, Cl, Br, I and resorcinol and catechol and its derivatives and bisphenol compounds become.

When Phenolic compounds are excluded Phenol the 2-methyl, 3-methyl, 4-methyl, 4-ethyl, 2,4-dimethyl, 2,5-dimethyl, 3,4-dimethyl, 2,6-dimethyl, 4-n-propyl, 4-n-butyl, 4-n-amyl, 4-tert-amyl, 4-n-hexyl or 4-n-heptyl-phenol or 2-methoxy-4- (2-propenyl) -phenol (eugenol) or 2-isopropyl-5-methyl-phenol (thymol) suitable.

When Mono- and polyalkyl- or aralkyl-halophenols can be used: methyl-, Ethyl, n-propyl, n-butyl, n-amyl, sec-amyl, n-hexyl, cyclohexyl, n-heptyl or n-octyl p-chlorophenol; also o-chlorophenol or methyl, ethyl, n-propyl, n-butyl, n-amyl, tert-amyl, n-hexyl or n-heptyl-o-chlorophenol.

Further can p-chlorophenol and o-benzyl, o-benzyl-m-methyl, o-benzyl-m, m-dimethyl, o-phenylethyl, o-phenylethyl-m-methyl, 3-methyl, 3,5-dimethyl, 6-ethyl-3-methyl, 6-n-propyl-3-methyl, 6-iso-propyl-3-methyl, 2-ethyl-3,5-dimethyl, 6-sec-butyl-3-methyl, 2-iso-propyl-3,5-dimethyl, 6-diethylmethyl-3-methyl, 6-iso-propyl-2-ethyl-3-methyl, 2-sec-Amyl-3,5-dimethyl-, 2-diethylmethyl-3,5-dimethyl-p-chlorophenol, or 6-sec-octyl-3-methyl-p-chlorophenol and also p-bromophenol and its derivatives, such as methyl, ethyl, n-propyl, n-butyl, n-amyl, sec-amyl, n-hexyl and cyclohexyl-p-bromophenol as well as o-bromophenol including tert-amyl, n-hexyl or n-propyl-m, m-dimethyl-o-bromophenol 2-phenylphenol, 4-chloro-2-methylphenol, 4-chloro-3-methylphenol, 4-chloro-3,5-dimethylphenol, 2,4-dichloro-3,5-dimethylpehnol, 3,4,5,6-tetrabromo-2-methylphenol, 5-methyl-2-pentylphenol, 4-Isopropyl-3-methylphenol, 5-chloro-2-hydroxydiphenylmethane.

Further can Resorcinol and its derivatives are used such as methyl, ethyl, n-propyl, n-butyl, n-amyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, Phenyl, benzyl, phenylethyl, phenylpropyl or p-chlorobenzylresorcinol and 5-chloro or 4'-chloro or 5-bromo or 4 '' - bromo-2,4-dihydroxydiphenylmethane.

As bis-phenol compounds, bisphenol A and 2,2'-methylene-bis (4-chlorophenol), 2,2'-methylene-bis (3,4,6-trichlorophenol [hexachlorophene], 2,2'-methylene Bis (4-chloro-6-bromophenol), bis (2-hydro xy-3,5-dichlorophenyl) sulfide, bis (2-hydroxy-5-chlorobenzyl) sulfide.

The non-cationic bactericidal component is in the oral care product in an effective plaque preventing amount, namely in an amount of 0.01 to 5% by weight, preferably about 0.03 to 1 wt.% And in particular in an amount of 0.25 to 0.5 wt.% Or at best, in an amount of 0.25 to 0.35% by weight, such as for example in an amount of 0.3% by weight in a dentifrice or preferably in an amount of 0.03 to 0.3% by weight and especially in one Amount of 0.03 to 0.1% by weight in a mouthwash or a liquid oral hygiene product. The bactericide is substantially water-insoluble, i. that his solubility in water at 25 ° C is less than about 1 wt% and may also be less than about 0.1 wt%.

The preferred halogenated diphenyl ether is triclosan. Preferred phenolic compounds are phenol, thymol, eugenol, hexylresorcinol, and 2,2'-methylene-bis (4-chloro-6-bromophenol), but triclosan is particularly preferred. Triclosan is mentioned as a bactericide in combination with an anticalculus agent which provides zinc ions U.S. Patent 4,022,880 and in combination with a copper compound in DE-PS 35 32 860 described. Triclosan is in combination with a potassium ion-containing, tooth insensitive agent in EU Patent 0 278 744 described. Further disclosed EU PS 0 161 898 the use of triclosan as an antiplaque agent in a toothpaste, formulated to contain a lamellar liquid crystal surfactant phase having fin pitches of less than 6.0 nm and which may preferably contain a zinc salt; Also in combination with zinc citrate trihydrate is triclosan according to EU PS 0 161 899 disclosed. The anti-bacterial enhancer or enhancing activator AVA, which increases the availability of the bactericidal agent to the oral regions and enhances the retention of the bactericide at these regions, is used to achieve this enhancement in amounts of from about 0.005 to about 4, and preferably from 0.1 to about 3 and in particular from 0.5 to about 2.5 wt.% Is used.

The AVA component is a polymer in the general sense, such as an oligomer, homopolymer, copolymer of two or more monomers, Ionomer, block copolymer, graft copolymer, cross-linked polymers and copolymers. The AVA component can be a natural or synthetic compound be that water-insoluble or preferably water or saline soluble or swellable e.g. be hydratable or swellable to form a hydrogel can. The weight average molecular weight is preferably in a range from 1 000 to around 1 000 000 and in particular in a range of 2,000 or 2,500 to around 250,000 or 500,000.

The antibacterial enhancer activator AVA contains at least one residue which increases the availability of the bactericide; this radical is an acid radical such as a sulfonic acid or phosphonic acid radical and in particular a phosphonic acid or carboxylic acid radical or a salt thereof, such as, for example, an alkali metal or ammonium salt. The enhancer activator further contains at least one organic moiety which increases the retention of the bactericide. There are several such radicals. The retention-promoting radicals have the general formula - (X) _n -R, where X is O, N, S, SO, SO ₂ , P, PO or Si and R is a hydrophobic alkyl, alkenyl, acyl, Aryl, alkaryl, aralkyl or heterocyclic radical or derivatives of these compounds having interten substituents, wherein n has the value of zero or 1.

The mentioned intert-substituted derivatives include substituents on the radical R, which are generally not hydrophilic and do not interfere with the desired mode of action of the AVA with regard to increasing the supply of the bactericide and its retention at the oral sites; such derivatives are halo radicals such as Cl, Br, J and carbo groups. Examples of such retention-enhancing group are listed in the following table: n X - (X) _n R 0 - Methyl, ethyl, propyl, butyl, isobutyl, t.-butyl, cyclohexyl, allyl, benzyl, phe nyl, chlorophenyl, xylyl, pyridyl, furanyl, Acetyl, benzoyl, butyryl, terephthaloyl, 1 0 Ethoxy, benzyloxy, thioacetoxy, phenoxy, Carbethoxy, carbobenzyloxy, N Ethylamino, diethylamino, propylamido, Ben cylamino, benzoylamido, phenylacetamido, south Thiobutyl, thioisobutyl, thioallyl, thio benzyl, thiophenyl, thiopropionyl, phenyl thioacetyl, thiobenzoyl, SO Butylsulfoxy, allylsulfoxy, benzylsulfoxy, Phenylsulfoxy, So ₂ Butylsulfonyl, allylsulfonyl, benzylsul fonyl, phenylsulfonyl, P Diethylphosphinyl, ethylvinylphosphinyl, Ethylallylphosphinyl, ethylbenzyl phosphinyl, ethylphenylphosphinyl, PO Diethylphosphinoxy, ethylvinylphosphinoxy, Methylallylphosphinoxy, methylbenzyl phosphinoxy, methylphenylphosphinoxy, Si Trimethylsilyl, dimethylbutylsilyl, di methylbenzylsilyl, dimethylvinylsilyl, Dimethylallylsilyl.

Of the the provision of the bactericide increasing Rest is one that contains the antibacterial reinforcing activator AVA with the bactericide to the oral surfaces, such as teeth and palate, adhering or substantive, adhesively cohesively or otherwise to the surfaces and thereby delivers the bactericide. The rest, who the Reteniton of the bactericide promotes these areas is generally one hydrophobic residue; this binds the bactericide to the enhancer activator and increased thereby the retention of the bacteri zids at the AVA and indirectly the oral surfaces. In some cases the binding of the bactericide takes place through physical integration through the AVA, especially if this is a cross-linked Polymeres whose structures have more districts for such Provide detention. The presence of a high molecular, rather hydrophobic cross-linked residues in the cross-linked polymers elevated the physical incorporation of the bactericide on or through the cross-linked AVA polymers.

Preferably For example, the AVA is an anionic polymer having a chain or a chain Chain skeleton, which has repeating units, each at least have a carbon atom and preferably at least one directly or indirectly attached univalent, the provision increasing Group and at least one directly or indirectly attached monovalent, increasing the retention Group that is geminal, vicinal or less preferred to others Way atoms, preferably carbon atoms bound in the chain contains. The polymer can also be used in some cases increasing residues and / or enhancing retention Radicals and / or other divalent atoms or radicals as connecting parts contained in the polymer chain, instead of or in addition to the carbon atoms or as cross-linked groups.

Examples of the AVA disclosed herein which do not contain groups for providing the bactericide and which also do not contain those for the retention of the bactericide can be chemically modified in a per se known manner to include AVA's containing both groups and Although contain a majority of these radicals. In the preferred polymeric AVA's, it is desirable to increase the substantivity and delivery of the bactericide to the oral surfaces which are repetitive Units in the polymer chain or in the backbone of the chain have at least about 10% and preferably at least 50%, and more preferably at least 80% to 95% or 100% by weight of the polymer of acidic residues which increase the availability.

wobei dieses Polymere jedoch nicht einen Rest enthält, der die Retention erhöht. Reste dieser Art sind jedoch in einem erfindungsgemäßen Poly(1-phosphonpropen) enthalten, dessen Einheiten die Formel haben:

In one embodiment not according to the invention, the antibacterial enhancer activator AVA is composed of a repeating unit polymer having one or more phosphonic acid residues which increase availability, which are attached to one or more carbon atoms in the polymeric chain. An example of such an AVA is a poly (vinylphosphonic acid) which contains radicals of the following formula:

however, this polymer does not contain a moiety that enhances retention. However, radicals of this type are contained in a poly (1-phosphonopropene) according to the invention whose units have the formula:

enthält, wobei Ph ein Phenylrest ist; der Phosphonsäurerest, der die Zurfügungstellung des Bakterizids erhöht und der Phenylrest, der die Retention verbessert, sind an vicinale Kohlenstoffatome in der Kette gebunden. Bevorzugt ist auch ein Copolymeres von beta-Styrolphosphonsäure mit Vinyl phosphonylchlorid, welches Einheiten der Formel III aufweist, die alternierend oder in zufälliger Verteilung mit Einheiten der Formel I auftreten oder eine Poly(alpha-styrolphosphonsäure), welche Einheiten der folgenden Formel enthält:

bei der die Zurverfügungstellung und die Retention erhöhenden Reste geminal an der Kette gebunden sind.A preferred AVA containing phosphonic acid residues is a compound containing poly (beta-styrene phosphonic acid) units of the following formula:

contains, wherein Ph is a phenyl radical; the phosphonic acid residue, which enhances the delivery of the bactericide, and the phenyl moiety, which enhances retention, are attached to vicinal carbon atoms in the chain. Also preferred is a copolymer of beta-styrenephosphonic acid with vinylphosphonyl chloride which comprises units of the formula III which occur alternately or in random distribution with units of the formula I or a poly (alpha-styrenephosphonic acid) which contains units of the following formula:

in which the residues which provide the provision and the retention are geminally bound to the chain.

These Styrenephosphonic polymers and their copolymers with other inert ethylenically unsaturated Monomers generally have a molecular weight in a range from about 2,000 to 30,000, and preferably from about 2,500 to 10 000. Such inert monomers interfere with the desired function of the AVA used copolymers not essential.

Other phosphonated polymers, such as poly (allylphosphonoacetate), phosphonated polymethacrylates and the like, and geminal diphosphonate polymers according to EU PS 0 321 233 may also be used as AVA, provided that they contain the abovementioned organic residues which promote the retention of the bactericide.

at an embodiment the oral hygiene product according to the invention have these an orally tolerable Carrier, an effective plaque preventing amount of a substantially water-insoluble non-cationic Bactericides and an antibacterial enhancer activator with one average molecular weight of about 1,000 to 1,000,000, the at least one of the provision enhancing functional group and at least one organic the Retention increasing Contains group, this AVA is not or substantially not water soluble Alkali or ammonium salt of a synthetic anionic linear polymeric polycarboxylate having a molecular weight of about 1 000 to about 1 000 000.

Another preferred embodiment of the invention is that the AVA is a synthetic anionic polymeric carboxylate. Although synthetic anionic polymeric polycarboxylates having a molecular weight of from about 1,000 to about 1,000,000, preferably from about 30,000 to 500,000, are not used with the anticalculus polyphosphate according to the invention, they are useful as an inhibitor of alkaline phosphatase enzymes U.S. Patent 4,627,977 has been used to optimize the anticalculus activity of linear molecular dehydrated polyphosphate salts. According to GB-PS 2 200 551 For example, polymeric polycarboxylates are disclosed as optional ingredients in oral care compositions containing linear, molecularly dehydrated polyphosphate salts and substantially water-insoluble non-cationic bactericides. It has also been found in connection with the present invention that such polycarboxylates are significantly effective in increasing the delivery and retention of non-ionic bactericides on tooth surfaces when other ingredients, namely, molecularly dehydrated polyphosphates, with which the polymeric polycarboxylates react, are absent; namely, when the ingredient with which the polymeric polycarboxylates interact is a non-cationic bactericide.

Synthetic anionic polymeric polycarboxylates and their complexes with various cationic germicides, zinc and magnesium are as anticalculus agents per se, for example from the U.S. Patent 3,429,963 . 4,152,420 . 3,956,480 . 4,138,477 and 4,183,914 known. The synthetic anionic polymeric polycarboxylates from this literature can, if they contain retention-promoting radicals or are modified in this way, be used in the oral hygiene products according to the invention.

The synthetic anionic polymeric polycarboxylates according to the invention are known and are often called free acids and preferably as partially or completely neutralized water-soluble alkali metal salts or ammonium salts used. Preference is given to 1: 4 to 4: 1 copolymers of maleic anhydride or maleic acid with other polymerizable ethylenically unsaturated monomers, preferably Methyl vinyl ether / Malesinsäureanhydrid having a molecular weight of about 30,000 to 1,000,000, in particular 30,000 to about 500,000. These copolymers are used, for example from the GAF Corporation under the trademark "Gantrez" e.g. as AN 139 with a molecular weight of 500,000 or as AN 119 with a Molecular weight of 250,000 and especially as S 97 in pharmaceutical Purity with a molecular weight of 70 000 sold.

Other polymeric polycarboxylates which are useful as AVA and which retain bactericidal retention or are modified accordingly are disclosed in U.S. Pat U.S. Patent 3,956,480 disclosed as the 1: 1 copolymers of maleic anhydride with hydroxyethyl methacrylate or N-vinyl-2-pyrolidone and 1: 1 copolymers of acrylic acid with methyl or hydroxyethyl methacrylate, isobutyl vinyl ether or N-vinyl-2-pyrolidone.

Other effective polymeric polycarboxylates are those mentioned above U.S. Patent 4,138,477 and 4,183,914 which contain retention-enhancing radicals or are modified accordingly, namely copolymers of maleic anhydride with styrene, isobutylene or ethyl vinyl ethers.

General suitable are polymerized olefinic or ethylenically unsaturated carboxylic acids with retention-promoting Rests containing an activated olefinic carbon-carbon double bond which reacts readily in the polymerization due to their Presence in the monomeric molecule, either in the alpha-beta position with respect to the carboxyl group or as part of a terminal Ethylene radical. Examples of such acids are acrylic, methacrylic, Ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropion, sorbin, alpha-chlorosorbin or cinnamic acid, beta-styrylacrylic, muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic, 2-benzylacrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric, maleic and their anhydrides. Other olefinic monomers containing such monomials Cabonsäuren are copolymerizable, are vinyl acetate, vinyl chloride or dimethyl maleate. Further, copolymers containing sufficient carboxylic acid salt residues for their water solubility contain.

Further suitable for the present invention are the so-called carboxyvinyl polymers which are used as toothpaste components in the U.S. Patent 3,980,767 . 3,935,306 . 3,919,409 . 3,911,94 and 3,711,604 are described. These are commercially available, for example, under the trademarks "Carbopol 934" and "-940" and "-941" from BF Goodrich. These products consist essentially of a colloidal water-soluble polymer of polyacrylic acid crosslinked with about 0.75 to 2.0 weight percent polyallyl sucrose or polyallyl pentaerythritol crosslinking agent, the crosslinked structure and crosslinks providing the desired increase in hydrophobicity or retention cause physical capture of the bactericide and act in a similar manner. The 2,5-dimethyl-1,5-hexadiene is an example of a much more effective retention enhancing crosslinking agent.

The Synthetic anionic polymeric polycarboxylate is essentially a hydrocarbon with preferably halogen and / or oxygen containing substituents and bonds in, for example, ester, Ether and OH groups and is present in the oral hygiene products in an amount of about 0.05 to 4, and preferably 0.05 to 3 and in particular from 0.1 to 2 wt.% Used.

The antibacterial enhancer activators AVA can natural anionic polymeric polycarboxylates which promote retention Contain residues. Carboxymethylcellulose and other binders such as gums and film-forming substances other than those mentioned above Providing heightening and / or retention-enhancing residues are unsuitable as AVA.

Examples of AVA with phosphinic acid residues and / or sulfonic acid residues to increase the availability are, for example, polymers and copolymers which contain units or groups derived by polymerization of vinyl or allyl phosphinic acid or sulfonic acids, which at the 1- or 2- or 3-carbon atom an organic retention-enhancing group are substituted and contain, for example, the above-mentioned general formula - (X) - _n -R. Mixtures of these monomers can be used and copolymers of these with one or more inert polymerizable ethylenically unsaturated monomers of the type described above in conjunction with synthetic anionic polymeric polycarboxylates.

polysiloxanes which residues contain the provision of the bactericide and the residues thereof promoting the retention thereof or are modified accordingly, can also be used as AVA. Further, as AVA ionomers suitable containing such groups. Such ionomers are in Kirk Othmer, "Encyclopedia of Chemical Technology ", 3rd Edition, Supplement Volume, pages 546 to 573. Other AVA's are Including polyesters, polyurethanes and synthetic and natural polyamides Proteins and proteinaceous materials such as collagen, poly (arginine) and other polymerized amino acids, if they have a retention of the bactericide-containing residues.

at an embodiment the oral hygiene product according to the invention the AVA has an average molecular weight of about 1,000 to about 1 000,000 and contains at least one functional residue, which is the provision of the bactericide increases and an organic radical that improves retention, wherein the oral care product no or substantially no water-soluble Alkali or ammonium salts of synthetic, anionic, linear, polymeric polycarboxylates having a molecular weight of about 1 000 to 1 000 000 contains.

This is according to the invention Oral care means a dentifrice with a content of about 0.3% by weight of bactericide, such as triclosan and about 1.5 up to 2% by weight of polycarboxylates as AVA.

It it is assumed that the polymeric AVA is generally an anionic film-forming material and on the tooth surface adheres and forms a continuous film on this surface and thereby prevents bacterial colonization on the tooth surface. It is possible, that this non-cationic bactericide forms a complex or other association with the AVA forms and thus gives a film of this complex on the tooth surface. The film-forming property of the AVA and the increased availability and the film-forming property of AVA and the enhanced retention of the bactericide on the tooth surface due to AVA causes that the tooth surfaces for bacterial Accumulations are unsuitable, in particular because the direct bacteriostatic effect of the bactericide the growth of bacteria in derogation. As a result, combinations of three different ones result Modes of action, namely once a reinforced one provision of the bactericide and, secondly, a long retention time the tooth surface and third, to prevent the deposition of bacteria the tooth surface, whereby the oral hygiene product according to the invention particularly good prevents a dental plaque. An identical plaque preventing Efficacy is the mucous membranes or the oral tissue in the palate area mediates.

According to the invention causes the orally tolerable Carrier, that yourself the substantially water-insoluble non-cationic Bactericide in an effective plaque-preventing amount in saliva solves.

The carrier used is an aqueous phase with a humectant. In a dental gel containing usually 5 to 30 wt.% Of a SiO ₂ Poliermittels water is usually present in an amount of at least 3 wt.% And generally from 3 to 35 wt.%, And as a humectant is preferably glycerol and or sorbitol in amounts of from 6.5 to 75 or 80% by weight of the dental gel. The amounts of sorbitol are generally based on the commercially available sorbitol in 70% aqueous solution.

Tooth gels containing from 0.25% to 0.35% by weight of bactericide do not require further additives for the carrier to solubilize the bactericide, although solubilizers are preferred. For example, if the bactericide is present in amounts less than 0.25% by weight, for example, 0.01 to 0.25% by weight, a solubilizing agent should be present to provide sufficient solubilization in saliva for plaque prevention possible. If the amount of the bactericide is above about 0.35 wt.%, Eg in a range of about 0.35 to 0.5 wt.% Or more or up to 5%, a solubilizing agent should be present, otherwise an essential part of the bactericide remains insoluble.

If it is the oral hygiene product is a toothpaste, the contains about 30 to 75 wt.% Of a polishing agent, so is the presence such a solubilizing agent is preferred.

If the oral hygiene product is present as a mouthwash or as a liquid oral hygiene product, so should the orally tolerable carrier at least one surfactant, an aromatic oil or contain a non-toxic alcohol, all of these components dissolving support the bactericide, again, the presence of such a solubilizing agent is preferred.

If in the oral hygiene compositions according to the invention a solubilizing agent is present, it will in general used in an amount of 0.5 to 20 wt.%, Already 0.5 % By weight if the amount of water-insoluble non-cationic Bactericide is low and, for example, about 0.3 wt.% Is. At higher Levels of bactericide, such as at least 0.5% by weight and in particular in the presence of polishing agents in an amount of 5 to 30% by weight, it is useful if at least 5% by weight and usually up to 20% by weight or more of solubilizing agent available. It may come to separations with toothpastes, though more than 5 wt.% Solubilizing agent are present.

The agent provided for the solubilization of the bactericide in saliva may be provided in the water / humectant carrier. Such solubilizing agents are humectants such as polyols, namely Propylengylkol, dipropylene glycol and hexylene glycol, "Cellosolve ^®" such as methyl cellosolve and ethyl cellosolve, vegetable oils and paraffins having at least 12 carbon atoms in the chain such as olive oil, castor oil, petrolatum and esters such as amyl acetate, ethyl acetate and benzyl benzoate. As propylene glycol, 1,2-propylene glycol and 1,3-propylene glycol is used. Essential amounts of polyethylene glycol, especially having a molecular weight of 600 or more, should be avoided since polyethylene glycol interferes with the bactericidal action of the non-cationic bactericide. For example, polyethylene glycol (PEG) 600 in combination with triclosan in a weight ratio of 25 parts triclosan to 1 part PEG 600 reduces the bactericidal effect of triclosan by a factor of about 16 over a product which does not contain polyethylene glycol.

The oral hygiene compositions according to the invention can be present as a tooth gel and contain a polishing agent based on SiO ₂ , in particular crystalline silica having a particle size of up to about 5μ, an average particle size of about 1.1μ and a surface area of up to 50 000 cm ² / g. preferably as a silica gel or colloidal silica or complex, amorphous alkali aluminosilicates.

When visually clear or opaque gels are desired, a colloidal silica is used as a polishing agent, such as that sold under the name "SYLOID ^® 72" or "SYLOID ^® 74" or "SANTOCEL ^® 100" as an alkali metal aluminosilicate complex. The gel-like structure and the refractive indices, which are close to the refractive indices of the gelling agent and the liquid components, are particularly suitable for such dental gels.

The Polishing material is in the toothpastes or tooth gels according to the invention in an amount of 5 to 30% by weight.

at an oral hygiene product according to the invention contains in the form of a toothpaste the carrier material a aqueous phase with a humectant, preferably glycerol and / or sorbitol, wherein the proportion of water in a range of 15 to 35 or 40 % By weight and the proportion of glycerol and / or sorbitol in a range from 20 to 25% by weight, and preferably 25 to 60% by weight, wherein the commercial one Sorbitol usually represents a 70% aqueous solution.

The oral hygiene products according to the invention can be present either as a toothpaste or, for example, in the presence of SiO ₂ -containing polishing agents as a tooth gel. The carrier component may contain polishing agents such as water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dehydrated or anhydrous dicalcium phosphate, calcium carbonate, aluminum silicate, hydrated alumina, silica, bentonite and mixtures thereof, as well as hard polishes such as calcined alumina and zirconium silicate or particulate resins as described U.S. Patent 3,070,510 such as melamine, phenol and urea-formaldehyde resins, and crosslinked polyepoxides and polyesters, with preferred polishing agents being insoluble sodium metaphosphate, dicalcium phosphate and hydrated alumina.

Many "water-insoluble" polishes are anionic and can even small amounts more soluble Contain ingredients. For example, as insoluble Sodium metaphosphate also uses Mandrell's salt and Kurrol's salt become. These metaphosphates show low solubility in water and are generally referred to as insoluble metaphosphates, but a small amount up to 4 wt.% Of soluble phosphates such as sodium trimetaphosphate contained, but this can be washed out. The insoluble Alkalimetaphosphates are mostly used as powder with a particle size, of which not more than 1% greater than 37μ is.

As the polishing material, for example, hydrated alumina which is not ionic and which has a particle size of less than 20μ at 85% and has a gibbsite structure and is an alpha-aluminum trihydrate can be used. The average particle size of gibbsite is 6 to 9μ, whereby the sieve analysis can be as follows: μ % <30 94-99 <20 85-93 <10 56-67 <5 28-40

The Polishing agent is generally in the toothpaste or in the dental gel in an amount of from 30 to about 75% by weight.

Toothpastes and tooth gels usually contain a natural or synthetic thickening or gelling agent in amounts of 0.1 to 10 and preferably 0.5 to 5 wt.%. Suitable thickeners are synthetic colloidal, clay-like, magnesium alkali silicate complexes, such as the Laponite types, where Laponite D is about 58.0% SiO ₂ , 25.4% MgO, 3.05% Na ₂ O, 0.98% Li ₂ O. and water and trace metals, has a specific gravity of 2.53 and a bulk density at 8% moisture of about 1.0.

Other suitable thickening or gelling agents are Irish moss, iota carrageenan, gum tragacanth, starch, polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, sodium carboxymethylcellulose, and in particular in the presence of SiO ₂ -Poliermitteln colloidal SiO ₂ as "SYLOID ^® 244" or "Sylodent ^® 15".

at Oral care products in the form of mouthwashes or liquid dentifrices becomes as a carrier usually used a water / alcohol mixture, wherein the weight ratio of Water to alcohol in the range of 1: 1 to 20: 1 and preferably at 3: 1 to 10: 1 and in particular 4: 1 to 6: 1. The total share of the water / alcohol mixture is usually within a range of 70 to 99.9% by weight. The alcohol used is ethanol or isopropanol. Humectants like glycerol and sorbitol be present in amounts of about 10 to 30 wt.%. Liquid oral care products usually contain 50 to 85 wt.% Water and can 0.5 to 20% by weight of alcohol and furthermore 10 to 40% by weight of a humectant such as glycerol and / or sorbitol. The alcohol and if necessary also the aroma oil support the resolution of the water-insoluble non-cationic bactericide.

The Non-cationic bactericide is essentially water-insoluble. According to the invention, however, with Help of the gain activator AVA such as with that in the mouthwash or in the liquid oral care product Polycarboxylate, the organic surfactant, the aroma oil or the non-toxic alcohol allows dissolution of the bactericide, so that this the mucous membranes, the palate area and the tooth surfaces reached. Surfactants and aroma oils support the resolution of the bactericide.

Organic surfactants are present in the oral hygiene products according to the invention in order to achieve an increased prophylactic effect and to allow a thorough dispersion of the antiplaque bactericidal in the oral area and also to better form the oral hygiene product of the invention in cosmetic terms. Surfactants used are anionic, nonionic or ampholytic surfactants which preferably have cleansing and foaming properties. Suitable anionic surfactants are water soluble salts of higher fatty acid monoglyceride monosulfates such as the sodium salt of monosulfated monoglycerides, hydrogenated coconut oil fatty acids, higher alkyl sulfates such as sodium lauryl sulfate, alkylaryl sulfonates such as sodium dodecylbenzenesulfonate, higher alkyl sulfoacetates, higher fatty acid esters of 1,2-dihydroxypropanesulfonate and substantially saturated higher aliphatic acylamides of lower aliphatic aminocarboxylic acids which have, for example, 12 to 16 carbon atoms in the fatty acid radical, alkyl or acyl radical. Examples of such compounds are N-lauroyl sarcosine and the sodium, potassium or Ethanolamine salts of N-lauroyl, N-myristoyl, or N-palmitoyl sarcosine, which are substantially soap-free. Such sarcosinates are particularly advantageous in oral care products, as they prevent the formation of acid in the oral cavity. Examples of water-soluble nonionic surfactants are condensation products of ethylene oxide with various compounds having reactive hydrogen atoms with hydrophobic, long-chain compounds, such as C ₁₂ - to C ₂₀ -Aliphaten, such as condensation products with hydrophilic Polyoxyethylenresten (ethoxamers) or condensation products of poly (ethylene oxides) with fatty acids, fatty alcohols or fatty amides and polyhydric alcohols such as sorbitan monostearate and polypropylene oxides.

The Surfactants are generally in an amount of 0.5 to 5 wt.%, preferably in an amount of 1 to 2.5% by weight.

If the oral care products in liquid Generally, they generally contain from 0.1 to 10 and preferably 0.5 to 5 wt.% Thickening or gelling agent.

In general, liquid oral care products do not contain a polishing agent. Nevertheless, eg according to U.S. Patent 3,506,757 about 0.3 to 2.0% by weight of a polysaccharide having a molecular weight greater than 1,000,000 containing an approximate 2: 1: 1: 1 ratio of mannose, glucose, potassium gluconate and acetyl groups as suspending or thickening agents in one liquid oral care products are then used, which then also contain 10 to 20 wt.% Of a polishing material such as hydrated alumina, dicalcium phosphate dihydrate, calcium pyrophosphate, insoluble sodium metaphosphate, anhydrous dicalcium phosphate, calcium carbonate, magnesium carbonate, magnesium oxide, silica and mixtures thereof.

It it is assumed that at the oral care compositions according to the invention the aqueous carrier in one solubilized in surfactant micelles mobile phase, excluding the gelling agent and any existing polish. The mobile dissolved phase of the oral care product is diluted with saliva, for example the triclosan precipitates. For example, it has been found that even in the absence of a particular solubilizer for triclosan in an amount from 0.25 to 0.35 wt.% and in the presence of the AVA as the polycarboxylate Sufficient triclosan is present in the area of the connective tissue to allow effective plaque prevention. Similar effects arise in other water-insoluble, non-cationic bactericides.

The Oral care according to the invention can also contain fluoride ion-supplying compounds called caries preventive agent in an amount of 25 to 5,000 ppm fluoride ions available. These are low to fully water soluble Compounds are, for example, inorganic fluorides such as soluble alkali metal or alkaline earth fluorides, copper, zinc or barium fluorides, and Sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate, Ammonium fluorozirconate, sodium monofluorophosphate, aluminum mono- and difluorophosphate and sodium calcium pyrophosphate, wherein alkali fluorides and stannous fluorides such as sodium fluoride and stannous fluoride and sodium monofluorophosphate and mixtures thereof are preferred.

The Amount of fluorine-providing compounds depends on the type of the concerned Connection, their solubility and from other parameters and is generally in one Range from 0.0005 to 3.0% by weight, based on the total composition. For dentifrices, e.g. a dental gel, should total 5 000 ppm F ions, based on the weight of the dentifrice present be, wherein also 300 to 2,000 ppm and preferably before 800 to about 1,500 ppm fluoride ions are preferred.

alkali metal fluorides are generally in an amount of 2 wt.% And preferably in a range of 0.05 to 1 wt.% Used in toothpastes. Sodium monofluorophosphate is generally used in amounts of from 0.1 to 3 and preferably used in an amount of 0.76 wt.%.

The Oral care according to the invention can contain other additives, such as whitening agents, preservatives, Silicones, chlorophyll compounds and ammonia-containing compounds, such as Urea and / or diammonium phosphate. Furthermore, suitable flavoring agents or sweetener be present, and usually in an amount of 0.1 to 5 wt.% or more. The aroma oils can like the surfactants the solvent power of the Bactericides also increase in the absence of surfactants.

The Oral care according to the invention can several times a day or even at daily intervals be used. They have a pH of 4.5 to 9 or 10 and generally from 5.5 to about 8 and preferably from 6 to 8, in particular from 6.5 to 7.6. Oral hygiene products with a pH value under 5 result in no damage.

The Oral care according to the invention can also incorporated in lozenges, chewing gum or other preparations For example, by putting it in a warm, gummy mass stirred or by taking the rubbery mass with a composition according to the invention coated, these preparations still the usual Additions, Plasticizer, sweetener or carbons.

in the Following, the invention will be explained in more detail by means of examples, all quantities, unless otherwise stated, on refer to the weight. protected In the examples, brands are also identified by the words "Wz".

Example 1

Two toothpastes according to the invention of the following composition were prepared: ingredients: Parts by weight: A B glycerin 10.00 - propylene glycol - 10.00 Sorbitol (70%) 25,00 25,00 Iota-carrageenan 0.60 0.60 Polycarboxylate (Gantrez S-97-Wz) 2.00 2.00 sodium 0.40 0.40 sodium fluoride 0.243 0.243 Sodium hydroxide (50%) 1.00 1.00 titanium oxide 0.50 0.50 Silica polish (Zeodent 113 Wz) 20.00 20.00 Silica thickener (Sylox 15 Wz) 5.50 5.50 sodium lauryl sulfate 2.0 2.0 water 31.507 31.507 triclosan 0.30 0.30 aromatic oil 0.95 0.95

The Toothpaste A gives triclosan to the teeth and mucous membranes substantially just as well as the toothpaste B, which is a solubilizing agent for triclosan contains. For this toothpaste according to the invention a special solubilizing agent is not required. A corresponding toothpaste lacking the polycarboxylate (Gantrez), is re the provision from Triclosan much worse.

When replacing triclosan by other bactericides such as phenol, thymol, eugenol and 2,2'-methylene-bis (4-chloro-6-bromophenol) or the polycarboxylate (Gantrez ^®) are replaced by other AVA activators, such as by Carbopol ^®, for example, Carbopol ^® no. 934, and polymers of alpha- or beta-styrene phosphonic acid monomers and copolymers of these monomers with one or other ethylenically unsaturated polymerizable monomers such as vinylphosphonic acid, which also gives improved results.

Example 2

The following liquid dentifrices A to D were tested for their uptake and retention of triclosan on saliva-coated hydroxyapatite (HA) discs according to the test procedure described below. The quantities are based on parts by weight. The dentifrices A and D are comparative examples. The dentifrices B and C are according to the invention. ingredients: A B C D Sorbitol (70% per solution) 30.0 30.0 30.0 30.0 glycerin 9.5 9.5 9.5 9.5 propylene glycol 0.5 0.5 0.5 0.5 sodium lauryl sulfate 20.0 20.0 20.0 20.0 sodium fluoride 0.243 0.243 0.243 0.243 aromatic oil 0.95 0.95 0.95 0.95 triclosan 0.3 0.3 0.3 0.3 water 56.507 54.507 54.507 54.507 Poly (beta styrene phosphonic acid) - 2.0 - - Poly (alpha-styrenephosphonic acid) - - 2.0 - polyvinyl alcohol - - - 2.0 Triclosan uptake in μ / g 31.0 174.0 86.0 36.0 Retention on triclosan initially: 183.0 after 30 minutes: 136.0 after 1 hour: 105.0 After 3 hours: 83.0

The Triclosan uptake and retention was after adjusting the pH to 6.5 with NaOH each on saliva-coated hydroxyapatite discs certainly.

The above values show that the solution D containing polyvinyl alcohol (without an AVA) triclosan uptake of only 36.0 μ / g shows what a recording of 31 μ / g in the control solution A without Additives resembles. in the In contrast, in the solution C results with an addition of Poly (alpha-styrenephosphonic acid) a shot of 0.86 μ / g, So twice as big Recording as in the solutions A and D while the solution B with polybeta-styrenephosphonic acid) one to five times higher Recording opposite the solution A and D shows, from which it can be deduced, that a vicinal substitution of the provision increasing the bactericide Restes shows better results. The above results further show the surprising good retention of triclosan on HA discs over a long time in solution B, the poly (beta-styrenephosphonic acid) having molecular weights of about 3,000 to about 10,000.

Example 3

The Effect of antibacterial enhancer activators (AVA) like of synthetic, anionic, linear polycarboxylates with respect to Recording, storage and release of water-insoluble, non-cationic Bactericides of tooth surfaces becomes in vitro on saliva-coated hydroxyapatite discs and with detached buccal epithelial cells determined, with the in vitro determination of release and restraint on oral surfaces corresponds in vivo.

to Determination of Release of Bactericide on Saliva-coated HA was thoroughly washed with HA obtained from Monsanto Co. washed with distilled water, taken after vacuum filtration and over Night at about 37 ° C dried. The dried HA was ground to a powder in a mortar. 150.0 mg of HA were in a tablet form or 6 minutes in one Pressed laboratory press with about 5 000 kg to 13 mm slices and 4 Hours at 800 ° C sintered.

By Parafilm stimulated saliva was in an ice-cooled beaker clarified by centrifugation at 15,000 g for about 15 minutes at 4 ° C and then with stirring Sterilized for one hour by UV irradiation.

Each sintered disk was watered in a polyethylene test tube and, after removal of the water, added with 2.0 ml of saliva. After an incubation period of about 12 hours at 37 ° C with constant shaking in a water bath, a salivary pellicle formed. Subsequently, excess saliva was removed and the discs were treated with 1.0 ml of a solution containing the liquid phase solution of the dentifrice with the bactericide (Triclosan); it was again incubated at 37 ° C with continuous shaking in a water bath for 30 minutes, after which the disc was transferred to a new test tube and mixed with gentle shaking with 5.0 ml of water. The disc was then placed in another tube and the wash repeated twice. The disc was then placed in a new test tube, avoiding entrainment of other liquid components, and vigorously shaken after addition of 1.0 ml of methanol and left at room temperature for 30 minutes to take up the adsorbed triclosan through the methanol. The methanol was then filtered off with suction and 5 minutes centrifuged in a Beckman microcentrifuge No. 11 at 10,000 U / m. Subsequently, the methanol was chromatographed for the bactericide, in all cases three samples were used.

to Determination of the retention of the bactericide on a saliva-coated HA disc was this with slurries of dentifrice treated as described above. The disc was after an incubation period of 30 minutes at 37 ° C from the slurry taken, washed twice with water and then again with saliva incubated, which was clarified by centrifugation. After another Incubation at 37 ° C under constant shaking within different time intervals The HA disks were removed from the saliva, whereupon the amount of bactericide (Triclosan), which was retained by the disc and which had been released to the saliva, chromatographically was determined.

To assess the delivery or release of bactericide to the buccal epithelial cells, delivery was determined to assess the effect of PVM / MA in delivering the bactericide (Triclosan) to the mucosa from a dentifrice. The epithelial cells were picked up by gently rubbing a wooden spatula on the mucosa and suspended in a buffer solution. As a buffer solution, a Resting Saliva Salts (Rss) buffer of 50 nM NaCl, 1.1 nM CaCl ₂ and 0.6 nM KH ₂ PO ₄ solution of pH 7.0 in an amount of 5 to 6 × 10 ⁵ cells / ml, using a hemocytometer to count the cell and stored until use in ice. A cell suspension of 0.5 ml, previously heated at 37 ° C in a water bath, was added with 0.5 ml of the antibacterial solution to be tested and incubated at 37 ° C. This mixture was diluted at least 10 times to reduce the surfactant concentration and to avoid destruction of the cell membranes by the surfactant. After incubation for 30 minutes, the cells were harvested by centrifugation at 5,000 rpm for 5 minutes, washed 3 times with the Rss buffer solution, and added with 1.5 ml of methanol, followed by vigorous shaking by chromatographic analysis of the bactericide.

Two dentifrices of the following composition were prepared, the numbers being by weight. The dentifrice A is a comparative example. The dentifrice B is according to the invention.

The uptake of triclosan in μ / g on the saliva-coated HA discs and in μ / g × 10 ⁵ epithelial cells is given in the following Table I for the oral hygiene product A without polycarboxylate and for the oral hygiene product B with carboxylate. Table I Oral care products HA discs Epithelial cells A 25.0 38.0 B 54.0 96.0

These Values clearly show that the In dentifrice B contained polycarboxylate the supply and the Inclusion of triclosan in both the HA discs and the Epithelial cells increased.

Similar Results were obtained with dentifrices containing 0.30 parts by weight Triclosan contained.

Example 4

• a) 0,2% Triclosan
• b) kein Polycarboxylat
• c) kein Propylenglykol
• d) 0,5% Zinkcitrat
• e) 2,5% Tensid
• f) Natriummonofluorphosphat

enthielt.Further experiments with the saliva-coated HA discs and epithelial cells with a modified oral care product B according to Example 3 with a content of 2.0% polycarboxylate and 0.20% triclosan, 10.0% propylene glycol and 2.0% sodium lauryl sulfate and an analogous formulated dentifrice B ', but containing 0.30% triclosan were compared with a commercial oral hygiene product C, which hydrated alumina as a polishing agent and

• a) 0.2% Triclosan
• b) no polycarboxylate
• c) no propylene glycol
• d) 0.5% zinc citrate
• e) 2.5% surfactant
• f) sodium monofluorophosphate

contained.

Further, a dentifrice C 'of the following composition was tested, which corresponded to the commercial dentifrice C, but trousers contained 0.30% triclosan. Composition of the dentifrice C ' Wt.% Sorbitol (70%) 27.0 sodium 0.80 Natriummonfluorphosphat 0.85 zinc citrate 0.50 sodium 0.18 water 16.47 hydrated alumina polish 50.0 ethanol 0.20 sodium lauryl sulfate 1.875 sodium dodecyl benzene sulfonate 0.625 triclosan 0.30 flavoring 1.20

There the dentifrices C and C 'in total Contain 2.5% by weight of surfactant, is more surfactant for the dissolution of Triclosan available, as in the dentifrices B and B ', which contain only 2.0 wt.%. at the dentifrices B and B 'is however, propylene glycol is present in the siliceous polishing agent, which in the dentifrices C and C ', the hydrated alumina as Contain polishes, so that a optimal solution done by Triclosan.

The benefit of the dentifrices B and B 'containing propylene glycol and polycarboxylate (Gantrez) is as compared to the dentifrices C and C' in the triclosan uptake by the saliva coated HA discs and in epithelial cells from the following Table II. Table II Dentifrice Recording in μ / g Epithelial cells at HA discs in μ / g × 10 ⁶ epithelial cells B 41.1 101.6 B ' 77.4 142.0 C 20.4 61.0 C. ' 42.6 100.0

Further trials with dentifrice B 'containing 0.3% triclosan and the presence of polycarboxylate and propylene glycol in a 50% dentifrice slurry to determine the retention of triclosan on saliva coated HA discs also demonstrated excellent retention over time, such as from the following Table III: Table III Time in minutes Retention of triclosan in μ / q on HA disks 0 70 30 60 60 70 120 65 180 57 240 59

The above values show that dentifrice containing triclosan with polycarboxylate and propylene glycol an increased Delivery of triclosan to the tooth surface and to the mucosa as well as an increased Retention resulted, whereby plaque is better prevented and the bactericidal effects occur better.

Example 5

For comparison, the following dentifrices according to the invention according to formulas A and B were prepared: ingredients: % by weight A B glycerin 10.00 - propylene glycol - 10.00 Iota-carrageenan Sorbitol (70%) 25,00 25,00 sodium 0.40 0.40 sodium fluoride 0.243 0.243 Titanium dioxide 0.50 0.50 polycarboxylate (Gantrez ^® S-97) 2.00 2.00 water 29.157 29.157 NaOH (50%) 2:00 2:00 SiO ₂ polish (Zeodent ^® 113) 20.00 20.00 SiO ₂ thickener (Silodent ^® 15) 5.50 5.50 Aroma 1.10 1.10 triclosan 0.50 0.50 sodium lauryl sulfate 2.00 2.00 ethanol 1.00 1.00

The Dentifrice according to formula A contains a carboxylate and 0.5 triclosan as an antiplaque bactericide and no solubilizing agent, while in formula B propylene glycol is present as a solubilizing agent.

One Dentifrice of formula A is with respect to the release of triclosan to the epithelial cells much worse than that in this regard significantly more effective dentifrice formulation B, which is clear the improved intake of triclosan proves.

Example 6

In order to determine how the dentifrices concerned affect the regeneration of dental plaque, subjects were tested according to the method of Addy, Wilis and Moran in J. Clin. Perio, 1983, Vol. 10, pp 89-99, wherein a placebo toothpaste (i) and a toothpaste according to the invention with 0.3 wt.% Triclosan, 10% propylene glycol (instead of 3% propylene glycol 600) and 2 % polycarboxylate (Gantrez ^® S-97) and a humectant is selected from propylene glycol and sorbitol (ii) were used, the compositions of the dentifrice are as follows: ingredients Parts by weight in% (i) placebo (ii) according to the invention Polyethylene glycol 600 3.00 - glycerin 25,00 - propylene glycol - 10.00 Sorbitol (70%) 41.617 25,00 Natriumcarboxyl methylcellulose 0.35 - Iota-carrageenan - 0.60 sodium benzoate 0.50 - sodium 0.20 0.40 sodium fluoride 0.243 0.243 SiO ₂ polish (Zeodent ^® 113) 18.0 20.0 SiO ₂ thickener (Sylox ^® x15) 5.50 5.50 water 3.00 28.757 Polycarboxylate (Gantrez ^® S-97) - 2.00 triclosan - 0.30 Titanium dioxide 0.50 0.50 sodium lauryl sulfate 1.20 2.50 flavoring 0.89 1.10 ethyl alcohol - 1.00 Sodium hydroxide (50%) - 2.00

Regarding the Dental plaque reduction was seen in the subjects using the dentifrice according to the invention (ii) have been treated the subjects treated with the placebo composition (i) were a significant decline of 20%.

There smaller amounts of propylene glycol that in toothpaste (ii) existing 0.3% Triclosan can dissolve similar ones Expect results when the amount of propylene glycol decreases to 0.5 parts by weight and the amount of sorbitol is increased to 39.5 parts by weight. equally can other solubilizing agents such as dipropylene glycol, hexylene glycol, Methylcellosolve, ethylcellosolve, olive oil, castor oil, petrolatum, amyl acetate, Ethyl acetate, glyceryl tristearate and benzyl benzoate instead of propylene glycol effectively increase the intake of triclosan to the mucous membranes. Furthermore, similar Results are expected when using propylene glycol or other solubilizing agents in the toothpaste (ii) containing 0.3% triclosan.

Example 7

The following two toothpastes were prepared according to the invention: ingredients weight parts A B glycerin - 20.00 propylene glycol 10.00 0.50 Sorbitol (70%) 25,00 19.50 Natriumcarboxyl methylcellulose - 1.10 Iota-carrageenan 0,600 - sodium 0.40 0.30 sodium fluoride 0.243 0.243 SiO ₂ polish (Zeodent ^® 113) 20.00 20.00 SiO ₂ thickener (Sylox ^® 15) 5.50 3.30 water 28.757 15.307 polycarboxylate (Gantrez ^® S-97) 2.00 2.00 triclosan 0.50 0.30 Titanium dioxide 0.50 0.50 sodium lauryl sulfate 2.50 2.00 flavorings 1.10 0.95 ethanol 1.00 - Sodium hydroxide (50%) 2.00 1.60

Improved results are also obtained in the above compositions when replacing triclosan with other bactericides mentioned above, such as phenol, thymol, eugenol and 2,2'-methylene-bis- (4-chloro-6-bromophenol) and / or the polycarboxylate (Gantrez) replaced by other AVA, such as by Carbopol ^®, (eg 934), polymers of monomeric alpha- or beta-Styrolphosphonsäuren and copolymers of these monomers styrenephosphonic with other ethylenically unsaturated polymerizable monomers such as vinylphosphonic acid.

Example 8

Dentifrices of the following composition according to the invention were prepared;

The mentioned above Toothpaste showed an increased Supply of triclosan to the tooth surfaces and to the mucosa, and in a much more effective way than corresponding toothpastes, where no polycarboxylate was present.

Example 9

The following toothpastes were prepared, the quantities being by weight: ingredients A B glycerin 22.00 10.00 Sorbitol (70%) - 17.00 sodium 1.00 1.00 Polycarboxylate (Gantrez ^® S-97) 2.00 2.00 sodium 0.20 0.20 sodium benzoate 0.50 0.50 Sodium monofluorophosphate 0.76 0.76 Dicalcium phosphate dihydrate 48.76 48.76 triclosan 0.30 0.30 sodium lauryl sulfate 1.20 1.20 flavorings 0.89 0.89 Water at 100

The above toothpastes give triclosan to those coated with saliva HA discs are more effective than corresponding toothpastes that have no Containing polycarboxylate.

Example 10

An antiplaque toothpaste was prepared from the following ingredients, the quantities being by weight: glycerin 15.00 propylene glycol 2.00 sodium 1.50 water 24.93 Vinyl methyl ether / maleic third copolymer (42% solution) 4.76 Sodium monofluorophosphate 0.76 sodium 0.30 insoluble sodium metaphosphate 47,00 Titanium dioxide 0.50 sodium lauryl sulfate 2.00 triclosan 0.30 flavorings 0.95

In the compositions according to the above example, improved results are also achieved when the triclosan is replaced by phenol or by 2,2'-methylenebis (4-chloro-6-bromophenol) or by eugenol and / or when the polycarboxylate (Gantrez ) are replaced by other AVA's, such as Carbopol ^®, for example, 934 or styrenephosphonic acid polymers having a molecular weight in a range from 3000 to 10,000, such as (for example, poly beta-styrene phosphonic acid), or copolymers of vinylphosphonic acid with beta-styrene phosphonic acid, and with poly (alpha-styrenephosphonic acid).

Example 11

Dentifrices (A: for comparison, B: according to the invention) were prepared which contained triclosan in their liquid phase and had the following composition in% by weight: ingredients A B Sorbitol (70%) 53.33 40,00 water 40.48 39,15 polycarboxylate (Gantrez ^® S 15%) - 13.33 NaOH (50%) - 1.33 saccharin 0.40 0.40 sodium fluoride 0.32 0.32 aromatic oil 1.47 1.47 sodium lauryl sulfate 3.33 3.33 triclosan 0.67 0.67

The concentration of the above components corresponds to a 1.33% toothpaste, with a 25% level of friction agent required to make a complete toothpaste. This incomplete toothpaste liquid phase was assayed for uptake of triclosan on saliva coated HA discs, the results being recorded in Table IV below: TABLE IV A B % Triclosan 0.67 0.67 Ionic strength (M / L) - calculated 0,375 - PH value 8.7 7.6 Triclosan uptake (undiluted in μ / g per slice) 55 122

The above results show a more than double increase in the uptake of triclosan with the formulation B, which polycarboxylate (Gantrez ^®) contains, with respect to the formulation A without polycarboxylate.

Example 12

It was able to survive the concentration and uptake of triclosan by HA discs 1 determines slurry of toothpaste and water, wherein a dentifrice (containing 0.5% Triclosan and 2.5% sodium lauryl sulfate, once with 25% hydrated silica, and 1.5% Gantrez ^® polycarboxylate S-: the aqueous phase of a 1 97) Formulation A - and on the other hand a toothpaste with 50% alumina and 1.5% polycarboxylate (Gantrez ^® S-97) formulation B - were used. The formulations A and B are both according to the invention. The results are shown in the following Table V. Table V μ / g triclosan ml Triclosanaufnahme liquid phase μ / q per slice A 1650 52 B 1905 74

The supernumerary liquid Phases of 1: 1 slurry toothpaste in water were in terms of triclosan concentration in the supernatant Phase and in terms of triclosan uptake on salivary coated HA discs determined. The results show that when used of 50% alumina abrasive substantially added the triclosan a 1: 1 dilution increased from 1 650 to 1 905 and thereby an increased Uptake of triclosan was made possible from 52 to 74.

Example 13

The following mouthwashes of the present invention have been prepared which reduce plaque formation by increasing oral uptake and retention of triclosan. ingredients A B C D e polycarboxylate (Gantrez ^® S-97) 0.24 0.25 0.25 0.25 0.25 glycerin 15.00 10.00 15.00 10.00 15.00 ethanol - - 12,00 12.50 - propylene glycol - 5.00 - 5.00 - polyoxyethylene / polyoxypropylene Block mixed polymer (Pluronic F108 ^®) - 2.00 - - - sodium lauryl sulfate - - 0.20 0.20 0.20 triclosan 0.10 0.10 0.06 0.06 0.03 aromatic oil 0.40 0.40 0.40 0.40 0.40 Water at 100

Example 14

• * Als Polysaccharid wurde ein hochmolekulares Polysaccharid verwendet, bei dem die Mannose-, Glucose-, Kaliumglucoronat- und Acetylreste in einem angenäherten Molverhältnis von 2:1:1:1 vorlagen.

The following oral dentifrice compositions of the invention have been prepared by increasing the uptake and retention of triclosan in the oral area, with amounts given by weight. ingredients A B glycerin 20.00 20.00 Polycarboxylate (Gantrez ^® S-97) 0.3 0.3 polysaccharide * 0.8 - sodium benzoate 0.5 0.5 sodium 0.5 0.5 water 61.3 73.1 sodium lauryl sulfate 3.0 3.0 insoluble sodium metasulfate 10.0 - anhydrous di calcium phosphate 1.0 - aromatic oil 2.5 2.5 ethyl alcohol - - triclosan 0.1 0.1

• The polysaccharide used was a high molecular weight polysaccharide in which the mannose, glucose, potassium glucoronate and acetyl residues were in an approximate molar ratio of 2: 1: 1: 1.

Likewise, good results are achieved when in the above compositions the triclosan is replaced by either phenol or by 2,2'-methylene-bis- (4-chloro-6-bromophenol), by eugenol or by thymol, or when the polycarboxylate ( Gantrez ^{®) ®} by other AVA's, such as Carbopol, for example, 934 or replaced by styrenephosphonic acid polymers having a molecular weight ranging from 3000 to 10,000, such as by poly-beta-styrene phosphonic acid, or copolymers of vinylphosphonic acid with beta-styrene phosphonic acid and poly (alpha-styrenephosphonic acid).

Claims (33)

Oral care products containing a) 0.01-5% by weight of a non-cationic bactericidal component whose solubility in water at 25 ° C is below 1% by weight, b) 0.005-4% by weight of an antibacterial enhancer activator (AVA c) an orally acceptable carrier which solubilizes the bactericidal component in an effective plaque-preventing amount in the saliva, wherein the oral hygiene product is free of tartar-preventing polyphosphate compounds ; the AVA has at least one residue which attaches or attaches to the AVA with the bactericide at the oral surfaces and thus increases the supply of the bactericide, and at least one residue which binds the bactericide to the AVA and thus increases the retention of the bactericide , contains; the providing-increasing radical is an acidic radical selected from the group of carboxylic, phosphonic, phosphinic and sulphonic acid radicals and their salts and mixtures; the retention-enhancing radical is an organic radical corresponding to the general formula - (X) _n -R wherein X is O, N, S, SO, SO ₂ , P, PO or Si and R is a hydrophobic alkyl -, alkenyl, acyl, aryl, alkaryl, aralkyl or a heterocyclic radical including the inertly substituted derivatives of these radicals, and n has a value of 1 or 0; and the AVA is an anionic polymer containing a plurality of the bactericidal-enhancing residues and the bactericidal-retention-enhancing residues. Oral care product according to claim 1, characterized in that it is a dentifrice with a content of 5 to 30 wt.% Of a SiO ₂ Poliermittels, wherein the bactericidal component in an amount of 0.25 to 0.35 wt.% And additionally at least one surfactant and a flavoring oil are present. Oral care product according to claim 1, characterized in that it is a dentifrice with a content of 5 to 30 wt.% Of a SiO ₂ Poliermittels, further wherein a solubilizing component is present in a sufficient amount for the solution of the bactericidal component in the saliva. Oral care product according to claim 3, characterized that the bactericidal component in an amount of 0.05 to below 0.25% by weight is present. Oral care product according to claim 3, characterized that the bactericidal component in an amount of about 0.35 to 5% by weight is present. Oral care product according to claim 5, characterized in that that the bactericidal component in an amount of more than 0.35 to 0.5% by weight is present. Oral care product according to claim 1, characterized that it is a dentifrice with a content of 30 to 75 wt.% a dental compatible water Polishing agent is. Oral care product according to claim 1, characterized that as a mouthwash or liquid dentifrice present and that the orally tolerable carrier a watery one carrier is at least one surfactant, a flavoring oil or a non-toxic Alcohol are present. Oral care product according to Claims 1 to 8, characterized that it contains 0.05 to 5 wt.% Of a surfactant. Oral care product according to Claims 1 to 9, characterized in that it contains an aromatic oil in an amount from 0.1 to 5 wt.% Contains. Oral care product according to claim 8, characterized in that that it is a mouthwash and that the aqueous carrier contains ethanol, wherein the weight ratio from water to ethanol in a range of 1: 1 to about 20: 1. Oral care product according to claim 8, characterized in that that it is a liquid A dentifrice is from 0.3 to 2.0% by weight of a polysaccharide containing a high molecular weight above 1 000 000, which Mannose, glucose, potassium glucuronate and acetyl residues in an approximate ratio of 2: 1: 1: 1 as suspending and thickening agents and 10 to 20 wt.% Of a Contains polishing agent. Oral care product according to claim 1 to 8, characterized characterized in that the bactericidal component is selected from the group of halogenated diphenyl ethers, halogenated salicylanilides, benzoic, halogenated carbanilides and phenolic compounds. Oral care product according to claim 13, characterized that the bactericidal component is a halogenated diphenyl ether is. Oral care product according to claim 14, characterized the halogenated diphenyl ether is a 2,4,4'-trichloro-2'-hydroxyphenyl ether is. Oral care product according to claims 1 and 3 to 6, characterized characterized in that the solubilizing agent in an amount of 0.5 to 50% by weight is present and is selected from the group consisting from propylene glycol, dipropylene glycol, hexylene glycol, methyl cellosolve, Ethyl cellosolve, vegetable oil and a paraffin containing at least 12 C atoms, amyl acetate, ethyl acetate, glyceryl tristearate and benzyl benzoate. Oral care product according to claim 16, characterized that the solubilizing agent is propylene glycol and in one Amount of 0.5% by weight is present. Oral care product according to claim 1 or 16, characterized characterized in that it is a dentifrice and a polishing agent contains that selected is from the group of sodium metaphosphate, tricalcium phosphate, dihydrate or anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, Calcium carbonate, aluminum silicate, hydrated aluminum oxide, silica, Bentonite and mixtures thereof. Oral care product according to claim 18, characterized that the polish dicalcium phosphate dihydrate or hydrated Alumina is. Oral care product according to claim 1 to 8, characterized characterized in that the antibacterial enhancer activator is an average Molecular weight of about 1000 to about 1 000 000 has. Oral care product according to claim 20, characterized that the anionic polymer is a repeating chain Having units, each of which has at least one carbon atom contains. Oral care product according to Claim 21, characterized that each unit at least one the provision of the bactericide increasing Remainder and at least one residue that increases the retention of the bactericide contains the same to the vicinal or to other atoms in the chain are bound. Oral care product according to claim 20, characterized that the provision of the bactericide increasing Radical is a carboxyl radical or a salt thereof. Oral care product according to claim 23, characterized that the antibacterial enhancer activator a copolymer of maleic acid or the anhydride with another ethylenically unsaturated polymerizable Is monomers. Oral care product according to claim 24, characterized the other monomer of the copolymer is a methyl vinyl ether in a molar ratio from 4: 1 to 1: 4 to the maleic acid or its anhydride. Oral care product according to claim 25, characterized in that the copolymer is a Molekularge weight of about 30,000 to 1,000,000 and is present in an amount of 0.1 to 2 wt.%. Oral care product according to claim 26, characterized the copolymer has an average molecular weight of has about 70,000. Oral care product according to claim 20, characterized that the provision of the bactericide increasing The rest is a phosphonic acid residue or a salt thereof. Oral care product according to claim 28, characterized that the antibacterial enhancer activator a poly (beta-styrenephosphonic acid) or a poly (alphastyrenephosphonic acid) or a copolymer of a of these styrenesphosphonic acids with another ethylenically unsaturated monomer. Oral care product according to claim 1, characterized that it is an orally tolerable Carrier, one effective plaque preventing amount of a substantially water insoluble non-cationic bactericidal component and an AVA with a average molecular weight of about 1,000 to 1,000,000 has, and there is no or essentially no water-soluble Alkali or ammonium salt of a synthetic anionic linear polymeric polycarboxylic acid having a molecular weight of about 1,000 to about 1,000,000. Oral care product according to claim 30, characterized that the bactericidal component in an amount of 0.25 to below 0.5% by weight is present. Oral care product according to claim 31, characterized that the bactericidal component is in an amount of 0.25 to about 0.35% by weight is present. Oral care product according to claim 30 or 31, characterized in that it contains a polishing agent based on SiO ₂ or a silicate.