JPH02288819A - Antiplaque antimicrobial composition for mouth - Google Patents

Abstract

PURPOSE: To obtain a composition for oral cavity which is composed of a water- insoluble noncationic antimicrobial, a specific antimicrobial increasing agent and a vehicle, possesses enhanced delivery and retention of antimicrobials and is useful for lowering generation of gingivitis. CONSTITUTION: This composition comprises (A) a substantially water-insoluble noncationic antimicrobial, e.g. halogenized diphenyl ether (particularly triclosan) and halogenized salicylanilide, (B) an antimicrobial increasing agent for enhancing delivery of the antimicrobial to oral cavity surface and its retention there, for example, a polymer having delivery-increasing groups (e.g. oxygen, phosphonic acid and carboxylic acid) and/or organic retentive increasing groups [e.g. O(X)n -R (X is 0, N and S; R is an alkyl, an aryl and an acyl; (n) is O and 1)], e.g. a poly (β-styrene-phosphonic acid, and (C) a vehicle useful for dissolving the antimicrobial in an amount showing dental calculus-resistant effect into saliva. The composition contains the component B in the range of 0.005-4wt.%.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to an antibacterial and antiplaque oral composition and toothpaste. More particularly, the present invention relates to oral compositions and dentifrices containing substantially water-insoluble, non-cationic antibacterial agents effective in inhibiting dental plaque.

(Prior Art) Dental plaque is a hard, calcified deposit that forms on teeth.
), it is a soft deposit that forms on the teeth. Unlike tartar, dental plaque can form on any part of the tooth surface, especially at the gingival margin. Besides being therefore unsightly, this contributes to the development of gingivitis.

It is therefore highly desirable to include in oral compositions antimicrobial agents known to reduce plaque. Cationic antibiotics are often suggested. Further, in US Pat. No. 4,022,880, Binnen et al., a compound providing zinc ions as an anti-dental system is mixed with an antimicrobial agent effective in retarding the growth of plaque bacteria. A wide variety of antimicrobial agents have been described along with zinc compounds, including cationic substances such as daanides and quaternary ammonium compounds, and non-cationic compounds such as halogenated salicylanilides and halogenated hydroxydiphenyl ethers.

European Patent Publication No. 0161,89 in combination with non-cationic antibacterial, anti-plaque halogenated hydroxydiphenyl ether, triclosan, zinc citrate trihydrate
No. 9 (Saxton et al.). Triclosan is also shown in European Patent Publication No. 0271.332 (Davis et al.) as a toothpaste ingredient containing a solubilizing agent, such as propylene glycol.

Cationic antibacterial substances such as chlorhexidine, benzethonium chloride, and cetylpyridinium chloride have been the subject of extensive research as antibacterial antiplaque agents.

However, they are generally not effective when used in combination with anionic materials. On the other hand, non-cationic antimicrobial substances are compatible with anionic components in oral compositions.

However, oral compositions are generally mixtures of numerous ingredients, and even substances that are generally neutral, such as humectants, have an oily quality that can affect the performance of such compositions.

Moreover, even non-cationic, antimicrobial agents have limited antiplaque efficacy when used in combination with commonly used filter substances, such as polyphosphate antidental agents. Both of these are British Patent Publication No. 220
No. 0551 (Gaffer et al.) and European Patent No. 0251
No. 591 (Jakunun et al.), as indicated in each specification.

Commonly assigned U.S. patent application Ser.
It has been shown that the anti-plaque efficacy is significantly enhanced by containing polyphosphate and AEA in the optimal amount and ratio (Problem to be Solved by the Invention) The present invention An advantage is that an oral composition is provided that is provided with a substantially water-insoluble, non-cationic, antimicrobial agent and AEA to inhibit plaque formation, wherein the oral composition provides an antimicrobial agent in the saliva. and an orally acceptable liquid vehicle effective to dissolve the oral cavity in an amount exhibiting an anti-plaque effect.

A further advantage of the present invention is that AEA enhances the delivery and retention of antimicrobial agents in small, but anti-plaque, amounts in the teeth and oral soft tissues.

Another advantage of the present invention is that it provides anti-plaque oral compositions that are effective in reducing the incidence of gingivitis.

SUMMARY OF THE INVENTION Other advantages of the present invention will become apparent upon consideration of the following detailed description.

According to a particular aspect of the invention, the present invention provides an anti-plaque effect of applying an anti-plaque amount of a substantially water-insoluble, non-cationic anti-microbial agent to the oral cavity surface, the anti-microbial agent enhancing the delivery and retention of the anti-microbial agent therein. 0005 to 4% by weight of the enhancer and an orally acceptable vehicle effective to dissolve the antimicrobial agent in saliva in an antiplaque amount, consisting essentially of a polyphosphate antidental agent. 3. Typical examples of water-insoluble, non-cationic, antibacterial agents that are desirable in consideration of anti-plaque effects, safety, and compatibility with oral compositions that do not contain are as follows.

halogenated diphenyl ether 2:4,4'-) v chloro-2-hydroxy-diphenyl ether (triclosan) 22-dihydroxy-55-dibromo-diphenyl ether halogenated salicylanilide 9 4 (5-dibromosalicylanilide 3.4.54lichloro Salicylanilide 3.4:5-
) dibromosalicylanilide 2.3,3.5-tetrachlorosalicylanilide 3,3.3.5-tetrachlorosalicylanilide 3.5-dibromo+:3'-)lifluoromethylsalicylanilide 5-n-octanoyl- 3-
Trifluoromethylsalicylanilide 3.5-dibromo-4-trifluoromethylsalicylanilide 1-'' 3.5-dibromo-3-trifluoromethylsalicylanilide (fluorophen) Benzoic acid ester p-Hydroxybenzoic acid methyl ester p -Hydroxybenzoic acid propyl ester p-Hydroxybenzoic acid propyl ester p-Hydroxybenzoic acid butyl ester Halogenated carboanilide 3.4.4'-Trichlorocarboanilide 3-Trifluoromethyl-4,4-dichlorocarboanilide 33. 4
-) Lichlorocarboanilide phenolic compounds (phenol and its homologs, mono- and poly-alkyl and aromatic halo (e.g. F, (J, Br, ■)
-7xnol, resorcinol and catechol, and their derivatives, and bisphenol compounds) Phenol and its congeners phenol 2-methyl-phenol 3-methyl-phenol 4-methyl-phenol 4-ethyl-phenol 2.4 -dimethyl-phenol 25-dimethyl-phenol 3.4-dimethyl-phenol 2.6-dimethyl-phenol 4-n-propyl-phenol 4-n-butyl-phenol 4-n-amyl-phenol 4-t-amyl- Phenol 4-n-hexyl-phenol 4-n-hebutyl-phenol 2-methoxy-4-(2-furo is nyl)-phenol (eugenol) 2-isopropyl-5-methylphenol (thymol) Mono- and poly- Alkyl and aralkylmethyl-p-chlorophenol ethyl-p-chlorophenol n-propyl-p-chlorophenol n-butyl-p-chlorophenol n-amyl-p-chlorophenol sec-amyl-p-chlorophenol n- Xyl-
p-chlorophenolcyclohexyl-p-chlorophenol n-hebutyl-
p-chlorophenol n-octyl-p-chlorophenol 0-chlorophenol methyl-0-chlorophenol ethyl-〇-chlorophenol, p-chlorophenol 〇-chlorophenol n-phthyl-0-chlorophenol n-amyl-0-chlorophenol t-amyl-0-chlorophenol n-hexyl-〇-chlorophenol n-hexyl-o-chlorophenol p-chlorophenol 0-benzyl-p-chlorophenol o-benzyl-m-methyl-p-chlorophenol o-
Benzyl-m,m-dimethyl-p-chlorophenol 0
-Phenylethyl-p-chlorophenol0-Phenylethyl-m-methyl-p-chlorophenol3-methyl-p-chlorophenol35-dimethyl-p-chlorophenol6-[-1+
-3-methyl-p-chlorophenol-6-n-propyl-3-methyl-p-chlorophenol 6-isopropyl-3-methyl-p-chlorophenol 2-ethyl-
3.5-) Methyl-p-chlorophenol 6-se
c-Butyl-3-methyl-p-chlorophenol 2-isopropyl-3,5-dimethyl-p-chlorophenol 6-diethylmethyl-3-methyl-p-chlorophenol 6-isopropyl-2-ethyl-3- Methyl-p-chlorophenol 2-sec-amyl-3.5-dimethyl-p-chlorophenol 2-cy:r-thylmethyl-3.5-dimethyl-
p-chlorophenol 6-sec-octyl-3-methyl-p-chlorophenol p-bromophenolmethyl-p-bromophenolethyl-p-bromophenol n-propyl-p-bromophenol n-butyl-p-bromophenol n-amyl-p-bromophenol sec-amyl-p-bromophenol n-hexyl-
p-bromophenolcyclohexyl-p-bromophenol 0-bromophenol t-amyl-0-bromophenol n-hexyl-〇-bromophenol n-propyl-m,m-dimethyl-〇-bromophenol 2-7 Enylphenol 4 -chloro-2-methylphenol 4-chloro-3-methylphenol 4-chloro-3,5-dimethylphenol 2,4-)chloro-3,5-dimethylphenol 3,,4,5,6-
Titranolomo 2-methylphenol 5-methyl-2-
pentylphenol 4-impropyl-3-methylphenol 5-chloro-
2-Hydroxydiphenylmethaneresorcinol and its derivatives resorcinol methyl-resorcinol ethyl-resorcinol n-propyl-resorcinol n-butyl-resorcinol n-amyl-resorcinol n-hexyl-resorcinol n-heptyl-resorcinol n-octyl-resorcinol n-nonyl-resorcinol Phenyl-Resorcinol Penzyl-Resorcinol Phenylethyl Resorcinol Phenylpro-0 Lou Resorcinol p-Chlorobenzyl-Resorcinol 5-Chloro-24-dihydroxydiphenylmethane 4-
Chloro-24-dihydroxydiphenylmethane 5-noromo2.4-dihydroxydiphenylmethane 4"-noromo2.4-dihydroxydiphenylmethane bisphenol compound bisphenol A 2,2'-methylenebis(4-chlorophenol)2.
2-methylenebis(3,4,6-)dichlorophenol)(hexachlorophene) 2,2'-methylenebis(4-chloro-6-bromophenol)bis(2-hydroxy-3,5-dichlorophenyl)sulfide bis(2 -Hydroxy-5-chlorobenzyl) sulfide non-cationic antibacterial agents are present in oral compositions in amounts exhibiting anti-plaque effects, generally from about 0.01 to 5% by weight in toothpastes.
Quantum is approximately 0.003 to 1%, preferably approximately 0.25
~0.5%, or from about 0.25% to less than 0.05%, most preferably from about 0.25% to less than 0.05%, such as from about 0.03%, or preferably from about 0.03% to 0.3% in mouthwashes or dissolution dentifrices. %, most preferably about 0.03-0.1%. Antibiotics are virtually water-insoluble. This means that its solubility in water at 5° C. is less than about 0.01 parts, and may even be less than about 0.1 parts.

A preferred halogenated diphenyl ether is triclosan. Preferred phenolic compounds are phenol, thymol, eugenol, hexylresorcinol, and 2,2-methylenebis(4chloro-6-bromophenol). A highly preferred antibacterial antiplaque compound is triclosan. Triclosan is a U.S. Patent Box 1I.
No. 022880 as an antibacterial agent in combination with anti-dentistry which supplies zinc ions, and German Published Patent Application No. 35
No. 32860, it is shown in combination with a copper compound.

In EP 0 278 744 it is indicated for use in combination with a dental analgesic containing a source of potassium ions.

Also, this is the lamellar space 6. European Patent Application No. 016189) No. 3 (Lane et al.) as an anti-plaque mulberry in a dentifrice composition containing a lamellar liquid crystal type surfactant phase of less than Q nm and optionally containing a zinc salt. , also shown in European Patent Application No. 0161899 (Saxton et al.) in toothpastes containing zinc citrate trihydrate.

An antimicrobial enhancer (AEA) that enhances the delivery and retention of antimicrobial agents to oral surfaces is present in the oral composition from about 0.0005% to about 4%, preferably from about 0.01% to about 3%, more preferably An amount effective to achieve the above enhancement is used, ranging from about 0.05% to about 2.5% (by weight).

AEA may be a simple compound (preferably a polymerizable monomer, more preferably a polymer; the term is more generic, e.g. an oligomer, a homophomer, a combination of two or more monomers). including copolymers, ionomers, block copolymers, graft copolymers, crosslinked polymers and copolymers, etc. AEA can be natural or synthetic and water insoluble or preferably water (saliva) soluble or swellable (hydratable, hydrogel forming)
It may be either. This has a (weight) average molecular weight of about 100 to about 1,000,000, preferably about 1000.
~about 1,000,000, more preferably about 2000
or 2.5000 to about 250,000 or 500
,000. The 3°AEA typically contains at least one delivery-enhancing group.
ing group), which are preferably acidic, such as sulfonic acids, phosphinic acids, more preferably phosphonic or carboxylic acids, or salts thereof, such as alkali metal or ammonium salts, and at least one organic retention enhancing groups (ret
tionenhancing group), preferably a plurality of both delivery-enhancing groups and retention-enhancing groups, the latter group preferably having the formula -(X)n
-R, in the formula, X haO, N, S, So
, SO2, P , PO Mataha sl Natoteari, R
is a hydrophobic alkyl, alkenyl, acyl, aryl,
alkaryl, aralkyl, heterocyclic residues, or inert substituted derivatives thereof, and n is zero or one or more. The above-mentioned ``inert substituted derivative'' refers to substituents that are generally non-hydrophilic and do not significantly interfere with the intended function of AEA as enhancing the delivery and retention of antimicrobial agents to oral surfaces. is meant to include, for example, halo, such as (J, Br, ■ and carbo. Examples of retention enhancing groups are summarized below.

(X)nR methyl, ethyl, propyl, butyl, inbutyl, t-
-1 tyl, cyclohexyl, allyl, benzyl, phenyl, cyclophenyl, xylyl, pyridyl, furanyl,
Acetyl, benzoyl, zotyryl, terephthaloyl, etc.

1 0 ethoxy, benzyloxy, thioacetoxy,
phenoxy, carboethoxy, carbobenzyloxy, etc.

N ethylamide diethylamine, propylamide 8,
Benzylamino, benzoylamido, phenylacetamide, etc.

S thiobutyl, thiobenzyl, thioallyl, thiobenzyl, thiophenyl, thiopropionyl, phenylthioacetyl, thiobenzoyl, etc.

SO butylsulfoxy, allylsulfoxy, benzylsulfoxy, phenylsulfoxy, etc.

SO3butylsulfonyl, allylsulfonyl, benzylsulfonyl, phenylsulfonylnato.

P diethylphosphinyl, ethylvinylphosphinyl, ethylallylphosphinyl, ethylbenzylphosphinyl, ethylfinylphosphinylnato.

PO diethylphosphinoxy, ethylvinylphosphinoxy, methylallylphosphinoxy, methylpencilphosphinoxy, methylphenylphosphinoxy, etc.

Trimethylsilyl, dimethylbutylsilyl, dimethylbenzylsilyl, dimethylvinylsilyl, dimethylallylsilyl, etc.

As used herein, the delivery-enhancing group essentially allows the AEA (carrying the antimicrobial agent) to adhere to or otherwise bind by adhesion, aggregation, or other forms of oral cavity (e.g., plaque and gingiva) surfaces. , by which we mean a device that delivers antimicrobial agents to surfaces of this type. Organic retention-enhancing groups (which are generally hydrophobic)
A, thereby pA
Improves retention of antimicrobial agents to the EA and indirectly to the oral surfaces. In some cases, especially if the AEA is a cross-linked polymer, the structure of which inherently increases the site for physical entrapment, the attachment of the antimicrobial agent occurs through its physical entrapment by the AEA. When a highly hydrophobic crosslinked moiety with a higher molecular weight is present in the crosslinked polymer, the crosslinked A
Physical entrapment of the antimicrobial agent into or by the EA polymer is further facilitated.

Preferably the AEA is each preferably at least 1
a monovalent delivery-enhancing group that is a chain or backbone comprising a repeating unit containing carbon atoms, and preferably at least one directly or indirectly attached side chain, and at least one directly or indirectly attached side chain. consisting of a monovalent retention-enhancing group which is a side chain attached to an atom in the chain, preferably a carbon atom, in a gem, vicinal, or less preferred manner. It is an anionic polymer. Although less preferred, the polymer has delivery-enhancing groups and/or retention-enhancing groups and/or other divalent atoms or groups conjugated in place of or in addition to the carbon atoms in the polymer chain. Alternatively, it can be contained as a crosslinked portion.

Examples of AEAOs described herein that do not contain both delivery-enhancing groups and retention-enhancing groups can be chemically treated by known methods to remove both such groups, preferably more than one such group. It is possible to obtain a preferable AEA containing
It will be understood that this is preferred. In the case of preferred polymeric AEAs, repeating units containing acidic delivery-enhancing groups in the polymer chain or backbone are at least 10%, preferably at least about 50%
, more preferably at least about 80% to 95% or 100% (by weight).

According to a preferred form of the invention, the number of AEA is 1 or 2.
The polymer comprises a repeating unit in which one or more phosphonic acid-based delivery-enhancing groups are attached to one or more carbon atoms in the polymer chain. 1 An example of this type of AEA is poly(vinylphosphonic acid) containing units of the formula:

1-(CH2-CH)PO3H except that it does not contain a retention enhancing group. However, this group will be present in poly(1-phosphonopropene) containing units of the formula:

II - [CH-CH) CH3PO3H2 A preferred phosphonic acid-containing AEA for use herein is poly(β-styrene phosphonic acid) containing units of the formula:

(wherein Ph is phenyl and the phosphonic delivery-enhancing group and the phenyl retention-enhancing group are attached to the vicinal carbon atom in the chain), or a unit of formula Ill is a unit of formula I above. a copolymer of β-styrene phosphonic acid and vinylphosphonyl chloride, or poly(α-styrene phosphonic acid) containing units of the formula (wherein the delivery-enhancing group and the retention-enhancing group are (geminally connected to the chain).

These phosphonic acid-based polymers, and co-serimers of these with other inert ethylenically unsaturated monomers, generally have a molecular weight of about 2,000 to about 30,000, preferably about 2
, 500 to about 10,000. This type of "inert" monomer is one that does not significantly interfere with the intended function of the copolymer used here as the AEA.

Other phosphonic acid-containing ions include, for example, phosphonated ethylene having units of the following formula [(CH2)14CHPo3H2].

(wherein n is an integer or numerical value giving the polymer a molecular weight of, for example, about 3,000); and sodium poly(butene-/l/1 diphosphonate) having units of the formula Other phosphonated polymers, such as poly(allyl phosphonoacet-1-), phosphonated polymethacrylates, and EP-A-032
The gem-diphosphonate polymers shown in US Pat. No. 1,233 can also be used as AEAs herein. However, of course they contain or are modified to contain the organic retention-enhancing groups described above.

In one aspect of the invention, the oral composition comprises an orally acceptable amount of a substantially water-insoluble, non-cationic antimicrobial agent and from about 1,000 to
an antimicrobial enhancer having a curved molecular weight of about 1,000,000 and comprising at least one delivery-enhancing functional group and at least one organic retention-enhancing group; has a molecular weight of about 1,000 to about 1,000
,000 of water-soluble alkali metal salts or ammonium salts of synthetic aniono-based linear polymeric polycarboxylic acids, or substantially free of them.

According to another preferred form, the AEA consists of a synthetic aionic polymeric polycarboxylate. 1 In the present invention, although it is not used to synergize with the polyphosphate anti-dental decay leaf, it has a molecular weight of about 1,000 to about 1,
000,000, preferably from about 30,000 to about 500
,000 synthetic anionic polymeric polycarboxylates have been used as alkaline phosphatase enzyme inhibitors in optimizing the anti-calculus efficacy of linear intramolecularly dehydrated polyphosphate salts (e.g., U.S. Pat. .627
, 977, the beauty shown in Farr et al.
GB 2200551 discloses that a polymeric polycarboxylate is an optional component in an oral composition comprising a linear intramolecularly dehydrated polyphosphate salt and a substantially water-insoluble non-cationic antimicrobial agent. It is shown as.

Furthermore, in the case of the present invention, if there is no other component with which the polymeric polycarboxylate acts synergistically (i.e. intramolecularly dehydrated polyphosphate), e.g. Polycarboxylates of this type have been found to be highly effective in enhancing the delivery and retention of nonionic antibacterial, antiplaque agents to tooth surfaces.

Synthetic anionic polymer polycarboxylate toners and their complexes with various fungicides, zinc, and magnesium have been used as anti-dentistry systems, for example, as disclosed in U.S. Pat.
, 429,963 (Schedrowski); U.S. Pat. No. 4,152,420 (Gaffer et al.); U.S. Pat.
, 956,480 (Dichter et al.); U.S. Pat.
No. 138,477 (Gaffer); and U.S. Pat.
No. 183,914 (Gaffer et al.).

The synthetic anionic polymeric polycarboxylates disclosed in several of these patents contain or should contain retention-enhancing groups (which, when modified, are understood to be useful in the compositions and methods of the present invention). Therefore, these descriptions are included in this scope and are cited herein by reference.

Synthetic anionic polymeric polycarboxylates for use herein are well known and often in their free acid form or preferably partially or more preferably completely neutralized water-soluble alkali metal salts (e.g. (potassium and preferably sodium) or ammonium salts. Preferred are 1:4 to 4:1 copolymers of maleic anhydride and other polymerizable ethylenically unsaturated monomers, preferably with a molecular weight (M, W,) of about 30,00.
0 to about 1,000,000, most preferably about 30
000 to about 500,000 methylvinyl/maleic anhydride. These copolymers are eg Gantrez, eg AN 139 (M
, W, 500,000).

AN 119 (M, W, 250,000); and preferably 5-97 Pharmaceutical (M, W, 70,00
0), CAF, Inc.

Other macromolecules (modified, 3q + )carboxylate containing or containing retention-enhancing groups that can act as AEAs include those shown in the aforementioned U.S. Pat. No. 3,956,480. such as maleic anhydride and ethyl acrylate, hydroxyethyl methacrylate, N-
1:1 copolymer with vinyl-2-pyrrolidone or ethylene (this is for example Monsanto EMA No. 1
103. M, W, 10,000 and EMA grade 61), and 1 of acrylic acid with methyl- or hydroxyethyl methacrylate, methyl or ethyl acrylate, isonotyl, imbutyl vinyl ether, or N-vinyl-2-pyrrolidone: 1 copolymer.

U.S. Pat. Nos. 4,138,477 and 4,183, supra.
Other useful polymeric dIJ carboxylates that contain or are modified to contain retention-enhancing groups include copolymers of maleic anhydride and styrene, isostyrene or ethyl vinyl ether. , polyacrylic acid, polyitaconic acid, and polymaleic acid, and M, W, 1,000 or so sulfoacrylic acid oligomers [Uuiroyal
available as ND-2].

Generally suitable are polymerized olefinic or ethylenically unsaturated carboxylic acids containing retention enhancing groups,
contains an activated carbon-carbon olefinic double bond,
Since this exists in the monomer molecule at the α-β position relative to the carboxyl group or as part of the terminal methylene group, it functions easily during polymerization. Examples of acids of this type are acrylic acid, methacrylic acid, ethacrylic acid, α-chloroacrylic acid, crotonic acid, β-acryloxypropionic acid, sorbic acid, α-chlorosorbic acid, cinnamic acid,
β-styrylacrylic acid, muconic acid, itaconic acid, citraconic acid, mesaconic acid, curtaconic acid, aconinol, α
-phenylacrylic acid, 2-benzylacrylic acid, 2-
cyclohexyl acrylic acid, angelic acid, lamberic acid, fumaric acid, maleic acid and their anhydrides.

Other different olefinic monomers that can be copolymerized with this type of carboxylic acid monomer include vinyl acetate, vinyl chloride, dimethyl maleate, and the like. The copolymer contains sufficient carboxylic acid groups to be water soluble.

Also useful here are U.S. Patent Box 3,980,767 (Chiyotsuk et al.) as a toothpaste ingredient; U.S. Patent Box 3,935,306 (Roberts et al.); U.S. Patent Box 3,919,409 No. (Terula et al.); U.S. Patent Box 39
No. 11.904 (Harrison et al.) and U.S. Patent Box 3.7
No. 11,604 (Coronei et al.), a so-called carboxyvinyl polymer. These are commercially available, for example, under the trademarks Carbopol 934.940 and 941 (B, F. Gudrich), and these products essentially contain about 0.0
．． 75 to about 2.0% cross-linked colloidally water-soluble polyacrylic acid polymers, the cross-linked structure and cross-links provide the desired retention enhancement through hydrophobicity and/or physical entrapment of the antimicrobial agent. bring. Polycarbophil is somewhat similar, but is polyacrylic acid crosslinked with less than 0.2% divinyl glycol, and because the proportion, molecular weight and/or hydrophobicity of this crosslinker is lower,
Little or no retention enhancement (2,5
-dimethyl-1,5-hexadiene is an example of a more effective retention-enhancing crosslinker.

Synthetic Anionic Polymers Hz +) Carboxylic Acid Groups -1 The component is primarily hydrocarbon, optionally including halogens, and 〇-containing substituents and bonds, such as those present in esters, ethers and OH groups; It is used in the compositions of the present invention at a weight of about 0.05 to 4%, preferably 0.05 to 3 inches, and more preferably 0.1 to 2 inches.

AEA may consist of a natural anionic polymer polycarbophil-1 containing retention enhancing groups. Carboxymethylcellulose and other binders, gums, and film-forming materials that do not contain the aforementioned delivery-enhancing and/or retention-enhancing groups are ineffective as AEAs.

Phosphinic and/or sulfonic acid delivery
Examples of AEAs containing enhancing groups include AEAs optionally substituted on one or two (or three) carbon atoms by organic retention enhancing groups, such as those having the formula -(X)n-R, as shown above. Mention may be made of polymers or copolymers containing units or moieties derived from the polymerization of vinyl or allyl phosphinic acids and/or sulfonic acids.

mixtures of these monomers, and one or more inert polymerizable ethylenically unsaturated monomers;
For example, copolymers with those described above for useful synthetic anionic polymeric polycarboxylates may also be used. As will be appreciated, in these and other polymeric AEAs useful herein, typically only one acidic delivery-enhancing group is attached to a particular carbon or other atom in the polymer backbone or a side branch thereof. ing. Side-based delivery
Modified polysiloxanes that contain or contain enhancing groups and retention enhancing groups can also be used as AEAs herein. Also effective as AEAs herein are those that contain delivery and retention enhancing groups, or contain (modified ionomers.Ionomers are Kirk, Ot.
hmer Encyclopedia of Chemi
cal Technology, 3rd edition, supplementary volume,
John Wiley & Sons, Edition 451984
, pp. 546-573. Also useful as AEAs herein are 71-lyesters, as long as they contain or are modified to contain retention-enhancing groups.
Polyurethanes and synthetic and natural polyamides, including proteins and proteinaceous materials such as collagen, poly(arginine), and other polymeric amino acids.

In one aspect of the invention, the average molecular weight is from about 1,000 to
Approximately 1,000,000 AEAs contain at least one delivery-enhancing group functional group and at least one organic retention-enhancing group, and materials containing these groups have a molecular weight of about 1.0
00 to about 1,000,000 water-soluble alkali metal or ammonium salts of synthetic anionic linear polymeric polycarboxylic acids.

A preferred oral composition in the present invention is a dentifrice containing about 0.3% by weight of an antimicrobial agent (e.g., triclosan) and about 15-2% by weight of polycarboxylate as AEA.

Without wishing to be bound by theory, AEA, particularly polymeric AEA, is generally an anionic film-forming substance that adheres to the tooth surface and forms a continuous film on the surface, thereby causing the surface of the tooth to form a continuous film. It is thought that this prevents bacteria from adhering to the surface. Non-cationic antimicrobials can form complexes or other forms of association with AEA, thus forming a film, such as a complex, on the tooth surface. The film-forming nature of AEA and the AEA-enhanced delivery and retention of antimicrobial agents on the tooth surface appear to make the tooth surface inhospitable to bacterial accumulation. This is particularly because the direct bacteriostatic action of antibacterial agents inhibits bacterial growth. This oral composition thus has a combination of three modes of action: 1) enhanced delivery, 12) long retention time on the tooth surface, and 3) prevention of bacterial adhesion to the tooth surface. is effective in reducing dental plaque. A similar anti-plaque effect is achieved on the soft tissues of the oral cavity at or near the gum line.

According to the invention, an orally acceptable vehicle is:
It is effective in dissolving a substantially water-insoluble non-cationic antibacterial agent in saliva without exhibiting an anti-plaque effect.

In oral compositions, the orally acceptable vehicle includes an aqueous phase that includes a humectant. - Generally about 5 to 30
For gel toothpastes containing heavy heirloom siliceous polishing agents, the water content is generally at least about 3% by weight, and usually about 3 to 3% by weight.
35 parts by weight, humectants, preferably glycerin and/or sorbitol, generally totaling about 65-75 parts by weight or 8 parts by weight.
(for oral compositions, gel dentifrices) 3, where the term sorbitol refers to a substance that is generally commercially available as a 70% aqueous solution.

The amount of antibacterial agent in gel toothpaste is approximately 0.25 to 0.3
At 55% by weight, no other ingredients are required to solubilize the antimicrobial in the oral vehicle.

However, the presence of this type of solubilizer is optional. The amount of antimicrobial agent is less than about 0.025 parts by weight, such as from about 0.001 to about 0.2 parts by weight.
At 55% by weight, a solubilizing agent should be present to ensure sufficient solubilization in saliva to exhibit an anti-plaque effect. If the amount of antimicrobial agent exceeds about 0.35% by weight, such as from about 0.35% to about 0.5% or more, such as 5%, a solubilizing agent should be present. Otherwise, a substantial portion of the antimicrobial agent will remain undissolved.

The presence of such solubilizing agents is also optional when the oral composition is a bacterial polish containing about 30-75% by weight of a dentally acceptable polishing agent.

When the oral composition is a mouthwash or liquid dentifrice, the oral vehicle comprises at least one surfactant;
Contains aromatic oils or non-toxic alcohols, each of which assists in solubilizing the antimicrobial; again, the presence of such solubilizing agents is optional.

If a solubilizing agent is present in the oral compositions of the present invention, it will generally be in an amount of about 0.5 to 20 times the amount of the substantially water-insoluble non-cationic antimicrobial agent (e.g., about 0
．． If the amount is up to 3% by weight, a small amount of about 2005 heavy economy is sufficient. There are relatively large amounts of antibacterial agents present, for example at least about 2005, and especially siliceous polishing materials, about 2
When present, it is desirable that the solubilizing agent be present in an amount of at least about 5% by weight, generally about 20% by weight or more. It should be noted that when more than about 50% solubilizing agent is present, the dentifrice tends to separate into liquid and solid portions.

The substance present or present to solubilize the antimicrobial agent in saliva can be included in the water-humectant vehicle. Solubilizers of this type include humectant polyols such as propylene glycol, cyfropylene glycol and hexylene glycol, cellosolves such as methyl cellosolve and ethyl cellosolve, vegetable oils and waxes containing at least about 12 carbon atoms in the straight chain, For example, olive oil, castor oil and trolatum
and esters such as amyl acetate, ethyl acetate and benzyl benzoate. As used herein, "propylene glycol" includes 2-propylene glycol and 1,3-propylene glycol. In particular, large amounts of polyethylene glycol with a molecular weight of 600 or more should be avoided. This is because polyethylene glycol exhibits the effect of inhibiting the antibacterial activity of non-cationic antibacterial agents. For example, polyethylene glycol (PEG) 600 together with triclosan 5 triclosan: I PEG 600
When present at zero weight ratio, the antimicrobial activity of triclosan is reduced by a factor of about 16 over that normally found in the absence of polyethylene glycol.

According to an aspect of the present invention, the oral composition, dentifrice, may be substantially gel-like, eg, a gel-like dentifrice. Gel-like oral preparations of this type contain Kaye varnish. Preferred polishing materials include crystalline silica - particle size of about 5 microns or less, average particle size of about 1.1 microns or less, and surface area of about 50000 Cn12/9 or less - silica gel, or colloidal silica, and composite amorphous aluminosilicate. Contains alkali metal salts.

When using electrophilically transparent or opacified gels, colloidal silica-based polishing A, 1. For example, the trademark Thyroid (5YLOID), for example Thyroid 7
2 and Siloy) '74, or the trademark Zantcell (
5ANTOCEL), strike f nl□ cell 10
Particularly useful are those commercially available as 0.0 or alkali metal aluminosilicate complexes (i.e., silica containing alumina bonded in MadoIJnx).

These are closely related to gel-like textures, as they have a refractive index that approximates that of gelling agent-liquid (including water and/or humectants) systems commonly used in dentifrices.

The polishing agent is generally a dentifrice that is an oral composition, such as a toothpaste or a gel composition.
It is present at a weight concentration of

In one aspect of the invention in which the oral preparation is a dentifrice, an orally acceptable vehicle is present which includes an aqueous phase containing a humectant, preferably glycerin and/or a dentifrice. Glycerin and/or sorbitol generally total about 20-75%, more typically about 25-60% by weight of the oral preparation, dentifrice. Exist in quantity. Again, the term sorbitol refers to a substance that is generally commercially available as a 70% aqueous solution.

In the present invention, the oral composition and dentifrice are substantially in the form of a spray, for example, a toothpaste.
e, dental cream), but if a siliceous polishing material is used (this is not common, as this type of material is generally not used in quantities greater than about 30 years), this may be It may be in gel form. The oral composition, dentifrice vehicle contains dentally acceptable polishing materials, examples of which are as follows. Water-insoluble sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dicalcium phosphate dihydrate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, calcium carbonate, aluminum silicate, Hydrated alumina, silica, bentonite and mixtures thereof with each other or with hard polishing materials such as calcined alumina and zirconium silicate, U.S. Pat.
Materials containing particulate thermosetting resins, such as melamine-phenol and urea-formaldehyde systems and crosslinked polyepoxides and polyesters, as described in Meikunsho No. 070,510 (published December 5, 1962).

Preferred polishing materials include insoluble sodium metaphosphate;
Contains dicalcium phosphate and hydrated alumina.

So-called "water-insoluble" polishing materials are anionic and also contain small amounts of soluble substances. For example, insoluble sodium metaphosphate is prepared by Dicti of Thorpe (Thorpe).
onary of Applied Cbemistr
1, Madre,], ) salts and Kurr salts, which may be prepared by any suitable method as set forth in 1, Madre, ], vol. 9, 4th edition, pages 510-511.
The form of insoluble sodium metaphosphate, known as ol, ) salt, is another example of a suitable material. These metaphosphates exhibit only a slight solubility in water and are therefore commonly referred to as insoluble metaphosphates (IHPs).3 They are contaminated with small amounts of soluble phosphate material, usually a few strips of impurity. For example, there are even quadruple economies. The amount of soluble phosphate material--in the case of insoluble metaphosphates, which may include soluble sodium trimetaphosphate--can be reduced or removed by washing with water, if desired. Insoluble alkali metal metaphosphate salts are generally used in powder form with particle sizes not exceeding 37 microns or more in size for the material.

Hydrated alumina is an example of a polishing material that is nonionic in nature. Generally, this means that the particles are small in size (i.e., at least about 85 particles are 20 microns or less) and that the gibbsite (
It is classified as α-alumina trihydrate) and is usually chemically expressed as Al2O3.3H20 or AA(○H)3. The average particle size of gibbsite is generally about 6-9 microns. Common grades have the following particle size distribution:

The polishing material is generally present in the gauze or gel silk composition in a weight range of about 30 parts to about 75 parts.

Toothpastes and gel toothpastes generally contain natural or synthetic thickening or gelling agents in proportions of from about 0.1 to about 10%, preferably from about 0.5 to about 5 parts. Suitable thickeners are synthetic colloidal alkali metal magnesium silicate complex clays, such as Laponite, marketed by Laporte Industries.
) (for example cp.

SP 2002. D). Analysis of Lavonite D is approximately 5800 in weight 5102, 2
5,40 Mg0.3.05% Na2O,0,9
8% L 120 and some water and trace metals. Its true specific gravity is 253, which gives an apparent bulk density (9//wle, at 8 cm moisture) of 10.

Other suitable thickening or gelling agents include: Irish Boke, Iotard Radinan, Tragacanthime, Starch, Polyvinylhyloritone, Hydroxyethylpro1-cellulose, Hydroxybutylmethylcellulose, Hydroxyethylcellulose (such as that available as Natrosol), Sodium Carboxymethylcellulose,
Particularly when siliceous polishing material is present, colloidal silica, e.g.
Sylodent) 15.

In aspects of the invention where the composition is a mouthwash or liquid dentifrice and is substantially liquid in nature, the vehicle for the mouthwash is generally a water-alcohol mixture. Generally, the weight ratio of water to alcohol is from about 1:1 to about 2081, preferably from about 3=1 to 10:1, and more preferably from about 4=1 to about 6:1. The total amount of water-alcohol mixture in this type of preparation is generally from about 70 to about 9
9.9 Heavy economy. The alcohols are non-toxic alcohols, such as ethanol or improper tool.

Moisturizers such as glycerin and sorbitol contain approx.
There may be an amount of 0 to 30 heavy economic conditions. Liquid dentifrices generally contain about 50 to 85 parts water, may contain about 0.5 to 85 parts by weight non-toxic alcohol, and about 10 parts by weight.
It may also contain humectants of ~20% weight, such as glycerin and/or nrubitol. As used herein, the term nrubitol refers to that which is generally commercially available as a 70% aqueous solution. Ethanol is the preferred non-toxic alcohol. Alcohols are believed to aid in the solubility of water-insoluble, non-cationic antibacterial agents, and the same is true for aromatic oils.

As mentioned above, non-cationic antimicrobials are substantially water-insoluble. However, in the present invention, the AEA present in the mouthwash or liquid dentifrice, such as polycarboxylate, together with organic surfactants, aromatic oils, or non-toxic alcohols assist in dissolving the antimicrobial agent, which may be present in the gingiva or in the gingiva. It is believed to assist in reaching the nearby oral soft tissues and tooth surfaces. Organic surfactants and/or aromatic oils may be optional ingredients in oral compositions, dentifrices, etc., to aid in the solubility of antimicrobial agents.

The organic surfactant enhances the prophylactic action of the anti-inflammatory antibacterial agent in the composition of the present invention1, assists in its adequate and complete dispersion throughout the oral cavity, and makes the composition of the present invention cosmetic-L. ℃・sso uke is also used to make something acceptable. The organic surfactant is preferably anionic, nonionic or amphoteric, and the surfactant is preferably a detergent that imparts detergency and foaming properties to the composition. Suitable examples of anionic surfactants are: Water-soluble salts of higher fatty acid monoglyceride monosulfates, such as sodium salts of monosulfate monoglycerides of hydrolyzed coconut oil fatty acids, higher alkyl sulfates,
substantially saturated higher aliphatic acylamides of lower aliphatic aminocarboxylic acid compounds, such as sodium lauryl sulfate, alkylaryl sulfonates, such as sodium dodecylbenzenesulfonate, higher alkyl sulfoacetates, higher fatty acid esters of 12-dihydroxypropanesulfonate, and lower aliphatic aminocarboxylic acid compounds; For example, fatty acids, those containing 12 to 16 carbon atoms in the alkyl or acyl group. Examples of the last mentioned amides are N-lauroylsarcosine, and N-lauroyl, N-myristoylmata are the sodium, potassium and ethanolamine salts of N-valmitoyl-lyrucosine, which are higher fatty acids that are used in soaps or It must be thrown away with materials that do not substantially contain such substances. The use of these sarconate compounds in the oral compositions of the present invention indicates that these substances reduce the solubility of enamel in acid solutions to some extent, as well as suppress acid production in the oral cavity due to the decomposition of carbohydrates. It is particularly advantageous because it shows significant long-term effects in Examples of water-soluble non-on surfactants are:
Condensates of ethylene oxide and various reactive hydrogen-containing compounds containing long hydrophobic chains (e.g. aliphatic chains of about 12 to 20 carbon atoms); these condensates ("ethoxamers") ) contain hydrophilic polyoxyethylene moieties, such as poly(ethylene oxide) and fatty acids, fatty alcohols, fatty amides, polyhydric alcohols (
(e.g. sorbitan monostearate) and polypropylene oxide (e.g. Pluron
ic) type substance].

The surfactant is generally about 0.5 to 5 times, preferably about 1
Present in an amount of ~25%.

When the oral composition is a liquid dentifrice, the natural or synthetic thickening or gelling agent is generally present in a proportion of from about 0.1% to about 10%, preferably from about 0.5% to about 5%.

Liquid toothpaste generally does not contain polishing agents.

However, as described in U.S. Pat. No. 3,506,757 (Zarlaman), polymers with a molecular weight greater than 1,000,000 are combined with mannose, glucose, potassium curcuronate and acetyl moieties in a ratio of approximately 2:111. Polysaccharides containing about 0.3 to 20% can be used as anti-settling and thickening agents in liquid dentifrices, in which case it is combined with about 10 to 20% of polishing materials such as hydrated alumina, dicalcium phosphate, etc.・Dihydrate, calcium pyrophosphate,
It may also contain insoluble sodium meclate, anhydrous dicalcium phosphate, calcium carbonate, magnesium carbonate, magnesium oxide, silica, mixtures thereof, and the like.

Without being bound by theory that the benefits of the present invention may be derived, it is believed that the aqueous humectant vehicle will normally be free of the mobile phase (i.e., gelling agents and polishing agents, if present in the dentifrice formulation). ) is thought to be solubilized within the surfactant micelles. Toothpaste Migration 41] The solution becomes diluted with saliva during use, which can cause triclosan to precipitate. Therefore, even if there is no special solubilizing agent for triclosan, the amount of triclosan is about 0.25 to 0.35 deuterons, AEA,
For example, it has been found that when polycarboxylates are present, there is sufficient triclosan present without having a superior anti-1*1 plaque effect on the soft tissues of the gum line.

Similar considerations apply to the other water-insoluble, non-cationic antibacterial agents described herein.

The above oral compositions and toothpastes contain fluorite ion sources or fluoride-donating ingredients as anti-caries agents (anti-caries agents).
may contain an amount sufficient to provide about 25 to 500011+1111 fluorite ions. These compounds may be slightly soluble (or even fully soluble) in water. Characterized by virtually no undesirable reactions.These substances include: inorganic fluoride salts, such as soluble alkali metal salts, alkali metal salts, such as sodium fluoride, fluoride. Potassium, ammonium fluoride, calcium fluoride, copper fluoride, such as cuprous fluoride, zinc fluoride, barium fluoride, sodium fluorosilicate, ammonium fluorosilicate, sodium fluorozirconate, ammonium fluorozirconate, mono Sodium fluorophosphate, aluminum mono- and di-fluorophosphate, and calcium sodium pyrophosphate alkali metal and tin fluorides, such as sodium fluoride and stannous, sodium monofluorophosphate (MFP), and their Mixtures are preferred.

The amount of fluoride-donating compound depends to some extent on the type of compound, its solubility, and the type of oral preparation, but it should be a nontoxic amount and generally contains about 0.0
005 to about 3.0%. In the case of dentifrice preparations, such as dentifrice gels, an amount of the above-described compound releasing up to about 5,000 pp+11 F ions based on the weight of the preparation: i:ji is believed to be sufficient. Minimum amounts of such compounds may be used if appropriate, but from about 300 to 2
．． 00011pm, preferably about 800 to about 1.5pm
Preferably, sufficient compound is used to release 0.00 ppm of fluorite ions.

Generally, in the case of alkali metal fluorides, this component will be up to about 2 times the weight of the preparation, preferably about
Exists in an amount of 1. In the case of sodium monofluorophosphate, the compound is about 0.01 to 3%, more generally about 0.
．． May be present in an amount of 76%.

As is customary, oral preparations are sold or otherwise distributed in appropriately labeled packages. For example, toothpaste gels are typically packaged in collapsible tubes, typically aluminum, lined lead or plastic, or other squeezable, pump or pressurized dispensing devices for dispensing the contents. To,
It is provided with a label that essentially states that it is a toothpaste gel or the like.

The oral preparations of the invention may contain various other substances, such as white pigments, preservatives, silicones, chlorophyll compounds and/or ammonia-based substances, such as urea, ammonium phosphate, and mixtures thereof. can. When present, these adjuvants are included in the preparation in amounts that do not substantially adversely affect the desired properties and properties. Significant amounts of zinc, magnesium and other metal salts and substances that are generally soluble and would form complexes with the active ingredients of the invention should be avoided.

Any suitable flavoring or sweetening agent may also be used. Examples of suitable aromatic ingredients are aromatic oils, such as sara mint,
are palmmint, wintergreen, satsafras, J
oils of corn, sage, eucalyptus, marjolan, garlic, lemon and orange, and methyl salicylate. Suitable sweeteners include sucrose, lactose, maltose, xylitol, sodium cyclamate, perilartine, AMP (
Aspartyl phenylalanine methyl ester), saccharin, etc. Preferably, the flavoring agent and the sweetener each or together constitute about 0.1 to 5 or more parts of the preparation. Furthermore, similar to surfactants, aromatic oils, together with surfactants or even in their absence, appear to aid in the solubilization of antimicrobial agents.

In a preferred form of the invention, the oral composition of the invention is applied preferably regularly to the enamel and especially to the soft tissues of the oral cavity at or near the gum line, e.g. daily or twice a day.
every day or every three days, or preferably 1 to 3 times a day, pH about 45 to about 9 or 10, generally about 55 to about 8,
Preferably from about 6 to 8 and most preferably from about 65 to
At about 75, it is administered for at least 2 weeks up to 8 weeks or longer. Even at a pH below 5, enamel is not demineralized or otherwise damaged. p[4 is adjusted with an acid (e.g. citric acid or benzoic acid) or a base (e.g. sodium hydroxide) or, for example, citric acid-1 benzoic acid-1 carbonate- or hydrogen carbonate-sodium, disodium hydrogen phosphate, It can be buffered with sodium dihydrogen phosphate or the like.

The compositions of the invention can be incorporated into lozenges or into chewing gum or other products, for example by stirring into a warmed gum base or by applying to the outside of the gum base; Examples of agents include pontianak gum, rubber latex, vinylite resin, etc., and desirably include conventional plasticizers or softeners, sucrose or other sweeteners, or carbohydrates such as glucose, sorbitol, etc.

The following examples further illustrate the nature of the invention, but it is to be understood that the invention is not limited thereto. All amounts and proportions stated herein and in the claims are by weight unless otherwise indicated.

Example 1 The following toothpaste was prepared.

Glycerin Propylene Glycol Sorbitol (70oI)) Iota Karagenan Gauntlets 5-97 Saccharin Sodium Fluoride Sodium Hydroxide (50 parts) Titanium Oxide Sodium Lauryl Sulfate Water Triclosan Aromatic Oil 25.00 0.60 2.00 0.40 0 .243 1゜00 0.50 2.00 31.507 0.30 0.95 10.00 25 ,00 2.00 0.40 0.243 1.00 2.00 31.507 0.30 0.95 The dentifrices described above deliver triclosan to teeth and gingival soft tissues essentially as well as dentifrices containing special solubilizers for triclosan. That is, no special solubilizing agent is required for the dentifrice of the present invention to be effective. Furthermore, the corresponding dentifrices without polycarbonate, Gauntlets, had substantially poorer triclosan delivery.

In the above example, triclosan could also be replaced with other antimicrobials described herein, such as phenol, thymol, eugenol and 22-methylenebis(4-chloro-6-bromophenol), and/or Gauntlets could be replaced with other AEAs. , such as 1:1 copolymers of maleic anhydride and ethyl acrylate, sulfoacrylic acid oligomers, carbopols (e.g. 93
4), and also by replacing polymers of α- or β-styrenephosphonic acid monomers and copolymers of these monomers with each other or with other ethylenically unsaturated polymerizable monomers, such as vinylphosphonic acid. The results were obtained.

Example 2 The following liquid phase dentifrice solutions were tested for triclosan uptake and retention on saliva-applied hydroxyapatite (HA) disks using the test method described in Example 1, with the following results. .

Sorbitol (70% solution) Glycerin Propylene Glycol LS aF Aromatic Oil Triclosan Water 30.0 0.5 20.0 56.507 30, O 0,5 0,95 54,507 30,0 9,5 0,95 0, 3 54,507 9,5 0,95 0,3 54,507 Polyvinyl alcohol NaOH 11tH Adjusted to 6,5 2.0 Initial 30 minutes, 1 hour, 3 hours 183.0 136.0 105.0 The above results are as follows: It is shown here that the solution containing polyvinyl alcohol rather than AEA (D) produced a triclosan uptake of only 36.0, very similar to the uptake of the control solution (A) without additives of 31.0. In contrast, solution (C) containing poly(α-styrene phosphonic acid) produced more than twice as much uptake as solutions (A) and (D), and the solution containing poly(β-styrene phosphonic acid) ( B) resulted in approximately 5 times the uptake of solutions FA) and (B). This further indicates that vicinal substitution of the delivery-enhancing group gives better results. The above results indicate that poly(β-styrenephosphonic acid) (molecular weight approximately 3
It is also shown that an unexpectedly good retention of triclosan on the HA disks was obtained over a long period of time with solutions CB) containing 10,000 to 10,000).

Example 3 The effects of synthetic anionic linear polycarboxylates on the uptake, retention, and release of water-insoluble, non-cationic antibacterial agents from tooth surfaces were investigated in vitro on saliva-applied hydroxyapatite discs and (Evaluated on exfoliated buccal epithelial cells.) In vitro evaluation correlates with in vivo delivery and retention on oral surfaces.

In order to investigate the delivery of antibacterial agents to saliva-applied hydroxyapatite disks, hydroxyapatite (HA) obtained from Monsando was thoroughly washed with distilled water and collected by vacuum filtration. Dry overnight at °C. The dried HA was ground with a mortar and pestle.

150,0]J of HA was inserted into the chamber of a KBr pellet die (Barnes Analytical, Stamford, Conn.) and pressed for 6 minutes at 10,000 lbs'' in a Carper Laboratory Press. The resulting 13 discs were sintered in a Thermoline furnace at 800°C for 4 hours.
) Total stimulated saliva was collected into a water-cooled glass beaker.

15. Saliva. Clarification was achieved by centrifugation in OOOXg for 15 minutes at 4°C. Sterilization of the clarified saliva was carried out by irradiating the sample with a UV lamp for 10 hours at 4° C. while stirring.

The sintered discs were hydrated with aqueous water in polyethylene test tubes. The water was then removed and 2.00 rut! I replaced it with saliva. A saliva film was formed by incubating the disks in a water bath at 7° C. overnight with continuous shaking. After this treatment, saliva is removed and solution 1 containing the antibacterial agent (triclosan) toothpaste liquid phase solution.
．． Discs were treated with 00ml and incubated in a water bath at 37°C with continuous shaking. After 30 minutes, the disk was transferred to a new test tube, and after adding 5.0 Om# of water, the disk was gently shaken with a portex. The discs were then transferred to new tubes and the washing process was repeated twice. Finally, the disk was carefully transferred to the new cheap, being careful not to transfer any liquid along with the disk. Then 1. OOmJ of methanol was added to the disk and stirred vigorously with a portex. The sample was left at room temperature for 30 minutes and the adsorbed triclosan was extracted into methanol. Next, suction the methanol with an aspirator,
10.00 Orp with Beckman Microfuuge 11
Clarification was achieved by centrifugation for 5 minutes at m.

After this treatment, the methanol is converted into H2H for antimicrobial detection.
Transferred to a PLC (High Performance Liquid Chromatography) vial. Triplicate samples were used for all experiments.

To examine the retention of antimicrobial agents on saliva-coated HA discs, saliva-coated HA discs were treated with the dentifrice slurry described above. After incubation for 30 minutes at 37°C, the HA discs were removed from the dentifrice slurry, washed twice with water, and then re-incubated with parafilm-stimulated whole human saliva clarified by centrifugation. After incubation at 37°C with constant shaking for various periods of time, the HA disks were removed from the saliva and the amount of antimicrobial agent (triclosan) retained in the disks and released into the saliva was determined by HPLC analysis. To assay the delivery of antimicrobial agents to oral epithelial cells, we measured 1°. It was measured. Oral epithelial cells were collected by scraping the oral mucosa with a wooden applicator stick.
ss) Buffer) (50nM・NaC41,
1 nM, CaC, d2. and 0.6 nM, KH2P
The cells were suspended in O4 pH 70) at 5-6 x 10'' cells/ml and stored in water until use.
0.5 ru of cell suspension incubated at 7°C
0.5 ml of the test antibacterial bath solution was added to e and incubated at 37°C. The antimicrobial solution in the incubation mixture was diluted at least 10 times to reduce the surfactant concentration and prevent disruption of cell membranes by the surfactant. After 30 minutes of incubation, cells were incubated at 5,000 rpm in a Beckman Microfuge 11.
Collected by centrifugation for 1 minute. Cells collected as pellets were treated with R,...,X buffer three times (kn+) and treated with 1.5 ml of methanol. The samples were mixed vigorously and
Antibiotics were analyzed by PLC method.

A toothpaste with the following composition was prepared.

Propylene glycol (1,2) Iota carrageenan Gantorezotsu 5-97 Titanium dioxide sorbitol (70%) Sodium fluoride sankarin sodium 10.00 0.75 0.50 30.00 0.332 0.40 0.75 2.00 0.40 Triclosan 0.20 0.20 Sodium lauryl sulfate 2,00 2.00 Aromatic oil 0.95 0.95
Ethyl alcohol 1,00 1
．． 00 water (appropriate amount) Total amount 100.00
The uptake of triclosan into saliva-applied hydroxyapatite discs and oral epithelial cells with and without the high molecular weight polycarboxylate Gantressot 5-97 is shown in Table 1 below. .

Table 1 A 25.0
38.08 54.0
9G,0 These results demonstrate that gantorenots (present in dentifrice B) significantly enhances the delivery and uptake of triclosan into saliva-applied hydroxyapatite discs and exfoliated oral epithelial cells. I made it.

Similar results were obtained when the toothpaste contained 0.30 parts of triclosan.

Example 4 In a test on saliva-applied hydroxyapatite discs and exfoliated oral epithelial cells different from those shown in Example 1 above, 2.00% Gantorenots 5-97 and 0.
．． Toothpaste B containing 20q6 triclosan, 1000% propylene glycol and sodium lauryl sulfate, and toothpaste (B') with the same composition except for the presence of 030% triclosan, containing a hydrated alumina-based polishing agent. A commercially available toothpaste (C) containing (a) 0.2% triclosan, (b) physically free of lentils, (C) free of propylene glycol, and (d) 0.5% zinc citrate. , (e) 2.5
% surfactant, (f) sodium monofluorophosphate and hydrated alumina-based polishing agent; and the following (C') which is the same as the commercially available toothpaste except that 0.30% triclosan is present. It was compared with toothpaste compositions.

Toothpaste C Sorbitol (70%) Sodium carboxymethyl cellulose Sodium monofluorosulfate Zinc citrate Sodium saccharin Hydration Alumina brushing material Ethanol Sodium lauryl sulfate Sodium dodecylbenzenesulfonate Triclosan Air freshener Chia 00 0°80 0.85 0.50 0 .18 50.00 0.20 0.625 0.30 1.20 Since toothpastes C and C' contain a total of 2.50% surfactant, toothpastes B and B contain 2.00%. In the case of ', a larger amount of surfactant is used to dissolve the triclosan. However, the propylene glycol present in toothpastes B and B' containing siliceous polishing materials (in toothpaste C containing hydrated alumina polishing materials)
and C') ensure optimal dissolution of triclosan.

We show that dentifrices B and B' (containing propylene glycol and Gauntlets) are superior to dentifrices C and C' in the uptake of triclosan on saliva-applied hydroxyapatite discs and in exfoliated oral epithelial cells. It is shown in Table 2 below.

Table 2 42.6 ioo,.

Toothpaste B' (0,
Additional experiments to measure the retention of triclosan on saliva-applied hydroxyapatite discs over time using 3% triclosan; Gauntlets; propylene glycol) revealed high levels of retention as shown in Table 3 below. Retention of triclosan was demonstrated.

Table 3 Adsorbed from a dentifrice slurry These results demonstrate that dentifrices containing triclosan, gantolats, and propylene glycol enhance the delivery and retention of triclosan to tooth surfaces and oral soft tissues, thereby increasing the resistance to Shows scales that improve plaque and antibacterial effects.

Example 5 For comparison, the following a and b were prepared.

Toothpaste Glycerin Propylene Glycol Iota Carrageenan Sorbitol (Part 70) Saccharin Sodium Heptonide Titanium Dioxide Gantolets 5-97 Water NaOH (50%) Zeoden) 113 (Silica-based polishing material) Soropunto 15
(Silica-based thickener) Aromatic agent Sodium triclosan lauryl sulfate Ethanol 10.00 0.60 25.00 2.00 29.157 2.00 20.00 5.50 2.00 Percentage 10.00 0.60 0. 40 0.50 29.157 20.00 5.50 2.00 O0 Prescription a is a toothpaste containing Gantoresotu, Tsuki Soricarboxylate, 05% triclosan as an antibacterial agent, and no solubilizing agent. be. When formulated, the solubilizer propylene glycol is present.

Although formulation a delivered less triclosan to oral epithelial cells, formulation a was significantly more effective.

The above results demonstrate the excellent delivery of triclosan toothpaste.

Example 6 To evaluate the effect of specific dentifrices on plaque regrowth, Aaay, Willis and Mo.
Ran.

J, C11n, Perio, 1983. Vol.
, 10. An in-home experiment was conducted according to the method described in Pages 89-99).

Test toothpastes included a placebo control (1) containing no triclosan, as well as 0.3% triclosan, 10
Propylene glycol (substitute for polyethylene glycol 600 in Part 3) and Gauntlets 5-
97, and the humectants Pro2 Rengelicol and Sorbitol (11)
was included. The formulations of these southern polishing agents are as follows.

Polyethylene glycol 600 Glycerin Propylene glycol Sorbitol (70 V) Sodium carboxymethyl cellulose Iota carrageenan Sodium benzoate Sodium saccharin Sodium fluoride Silica-based polishing material (Zeoden) 113) Silica-based thickener (Sironx 15) Water Gauntlets 5-97 Triclosan Titanium dioxide Sodium lauryl sulfate Aromatic oil Ethyl alcohol Sodium hydroxide (50 units) 3,00 4, ], 617 0,35 0,50 18,00 3,00 0,50 1,20 0,89 040 20,00 28,757 2,00 2,50 '00 2,00 Placebo (1) per volunteer's teeth regarding plaque reduction
In comparison, the present invention (11) showed a significant reduction of 20%.

If the amount of propylene glycol is reduced to 0.05 parts and the amount of sorbitol is increased to 395 parts, since a smaller amount of propylene glycol can dissolve the 0.3% triclosan present in toothpaste (11). Similar results are expected. Similarly other solubilizers, dipropylene glycol, hexylene glycol, methyl cellosol,
Ethylcellosols, olive oil, castor oil, R-trolatum amyl acetate, ethyl acetate, chryceryl tristearate, and benzyl benzoate can be used in place of propylene glycol to effectively deliver triclosan to oral soft tissues.

Furthermore, similar results are expected when propylene glycol and other solubilizers are removed from the toothpaste (11) containing 0.3 triclosan.

Example 7 The following dentifrices according to the present invention were prepared.

AB Glycerin 200
0 Propylene glycol 10,00
0.50 Sorbitol (70%)
25.00 19.50 Sodium carboxymethyl cellulose - 110 Iota carrageenan 0.600 Sodium saccharin 0.40 0.30 Sodium fluoride 0.243 0.
243 Silica-based polishing material (Zeopunt 113) 20
．． 00 20.00 Silica thickener (Silosox 15) 5,50 3.00 Water
28.757 15.307
Gauntlets 5-97 2.00
2.00 Triclosan Q, 5
0 0.30 Titanium dioxide 7
0.50 0.50 Sodium lauryl sulfate
2,50 2.00 Aromatic oil
1,10 0.95 ethanol
1.00 Sodium hydroxide (50%
) 2,00 1.60 and/or Gauntlets with other AEAs, such as 1:1 copolymers of maleic anhydride and ethyl acrylate, sulfoacrylic acid copolymers, carbopols (e.g. 934), α- or β - similarly improved results by substitution of polymers of styrene phosphonic acid monomers and copolymers of these styrene phosphonic acid monomers with each other or with other ethylenically unsaturated polymerizable monomers, such as vinylphosphonic acid; is obtained.

Example 8 The following toothpaste was prepared.

In the above example, replacing triclosan with other antimicrobial agents described herein, such as phenol, thymol, eugenol and 2,2'-methylenebis(4-chloro-6-bromophenol), alpha-alumina trihydrate propylene Glycol sorbitol (70 parts) /l800 Sodium lauryl sulfate Sodium saccharin Sodium hydroxide (50 parts) Air freshener Irish blur 2.00 0.30 1,00 2.13 2.13 0.95 Titanium dioxide triclosan 0.30 0.30 The above dentifrices delivered triclosan to teeth and gingival soft tissue areas substantially more effectively than corresponding dentifrices in which Gauntlets, polycarboxylates, were not present.

Example 9 The following toothpaste was prepared.

Part 22.00 10.00 17.00 1.00 2.00 0.20 0.50 0.76 48.76 0.30 1.20 0.89 Total amount 100.00 Glycerin sorbitol (70 parts) Sodium carboxymethyl cellulose 1.00
Gantorezotsu 5-97 2.00 Saccharin sodium 0.20 Sodium benzoate 0.50 Sodium monofluorophosphate 0.76 Dicalcium phosphate dihydrate 48.76 Triclosan
0.30 Sodium lauryl sulfate
1.20 Air freshener 0
．． 89 Water (appropriate amount) Total amount 100.00 The above dentifrice is more effective than the corresponding dentifrice that does not contain Gantrez, polycarboxylate, and triclosan is delivered to a hydroxyapatite disc by saliva application.

Example 10 The following anti-plaque dentifrice was prepared.

Glycerin Propylene Glycol Carboxymethyl Cellulose Sodium Aqueous Part 15.00 2゜00 1.50 24.93 Sodium Monofluorophosphate 0
．． 76 Saccharin Sodium
0.30 insoluble sodium metaphosphate
47゜O〇Titanium dioxide
0.50 Sodium lauryl sulfate
2. O.

Triclosan 0.
30 fragrance 0.
95 In the example above, triclosan is substituted with phenol, 2
．． When replacing 2'methylenebis(4-chloro-6-/7'romophenol), eugenol and thymol, and/or replacing Gantrett with other AEAs, such as carbopols (e.g. 934), or with molecular weights from about 3,000 to 10,000 styrene phosphonic acid polymers, such as poly(β-styrene phosphonic acid), copolymers of hinylphosphonic acid and β-styrene phosphonic acid, and poly(α-styrene phosphonic acid), or sulfoacrylic acid oligomers, or maleic anhydride and Improved results are also obtained when replacing with a 1=1 copolymer of ethyl acrylate.

Example 11 Mobile phase composition of toothpaste containing triclosan (%
) Water Gantressot 5 (15 inches) NaOH (50%) Saccharin Sodium fluoride Aromatic oil Sodium lauryl sulfate Triclosan 40.48 39 15 13.33 1.33 0.40 0.40 0.32 0.32 1.47 1 .47 3.33 3 33 0.67 0.67 The concentration of the above components is 133% of the Minami brushing agent level, considering the level 25 of the polishing material necessary for preparing the finished toothpaste.

The mobile phase of the above toothpaste formulation was investigated for triclosan uptake into saliva coated HA discs. The results are shown in the table below, which shows the uptake of triclosan by saliva-applied hydroxyapatite (HA) disks from diluted and undiluted dentifrice transfer.

Example 12 Triclosan concentration in supernatant of 1:1 dentifrice/water slurry and uptake of triclosan by HA 2!5 Hydrated Alumina + 1.650
5215 Gantreno S-9
7 50 Thialumina triclosan thionic strength (lvi/L) (calculated value) Uptake of toothpaste 1 of the above toothpastes increased by more than 2 times compared to formulation A without Gantresot:
The supernatant of the dentifrice/water slurry was examined for the concentration of triclosan in the supernatant and the uptake of triclosan into saliva-coated HA discs. The results show that triclosan increases substantially under low dilution conditions when using a 50% alumina-based polish (from 1,650 to 1,905).
This resulted in a substantial increase in triclosan uptake (5
2 to 74).

Example 13 The following mouth rinses are effective in reducing plaque by increasing the uptake and retention of triclosan on the surfaces of the oral cavity.

Effective in reducing dental plaque.

Glycerin Gantolets S-97 20,020,0 0,30,3 Gantolets 5-97 Glycerin Ethanol Propylene Glycol 0.24 15.00 Sodium Lauryl Sulfate Triclosan 0.10 Aromatic Oil 0.40 0.25 0.25 0. 25 02510.00
15.00 10.00 15.0012.50 1
2.50 5.00 - 5.00 0.20 0.10 0.06 0.40 0.40 0.20 0.20 0.06 0.03 0, /10 0. /10 Example 14 The following liquid dentifrices also enhance the uptake and retention of triclosan on oral surfaces: Sodium L-benzoate Sankarin Sodium Water Sodium Lauryl Sulfate Insoluble Sodium Metaphosphate Anhydrous Dicalcium Phosphate Aromatic Oil Ethyl Alcohol Triclosan 0.5 0.5 61.3 3.0 10.0 1.0 2.5 0.1 0.5 0.5 73.1 3, [1 2,5 0,1 0,5 0,5 71 ,6 3,0 10,0 2,5 2,5 10,1 0,1 In the above example, triclosan is replaced with phenol, 22'
-methylenebis(4-chloro-6-bromophenol)
, eugenol and thymol, and/or gantolenots with other AEAs, such as carbobols (e.g. 934), or with a molecular weight of about 3,
000-10,000 styrene phosphonic acid polymer,
For example, substituted with poly(β-styrenephosphonic acid), copolymers of hinylphosphonic acid and β-styrenephosphonic acid, and poly(α-styrenephosphonic acid), or sulfoacrylic acid oligomers, or 1:1 copolymers of maleic anhydride and ethyl acrylate. Improved results are also obtained when

Although the invention has been described in terms of particular preferred forms, it will be understood that alterations and modifications that are obvious to those skilled in the art are within the scope of the invention and the claims.

Claims (1)

[Scope of Claims] 1. An anti-plaque effective amount of a substantially water-insoluble, non-cationic antimicrobial agent, an antimicrobial enhancer that enhances the delivery and retention of the antimicrobial agent to oral surfaces, about 0.005%. ~4
% by weight and an orally acceptable vehicle effective to solubilize the anti-plaque agent in saliva in an anti-plaque amount, and which is substantially free of polyphosphate anti-calculus agents. . 2. The oral composition is a toothpaste containing about 5 to 30% by weight of a siliceous brushing material, and the antibacterial agent is about 0.25 to 0.3% by weight.
2. The oral composition of claim 1, present in an amount of 5% by weight, and wherein at least one surfactant and a fragrance oil are present. 3. The oral composition is a dentifrice containing about 5 to 30% by weight of a siliceous brushing material, and the antibacterial agent is present in an amount of about 0.01 to 5% by weight, and the oral composition contains an antibacterial agent. 2. The oral composition of claim 1, comprising an amount of solubilizing agent sufficient to dissolve the solubilizing agent in saliva. 4. The oral composition of claim 3, wherein the antimicrobial agent is present in an amount from about 0.05% to less than about 0.25% by weight. 5. The oral composition of claim 3, wherein the antimicrobial agent is present in an amount from greater than about 0.35% to about 5% by weight. 6. The amount of antibacterial agent exceeds about 0.35% by weight to about 0.5%
6. The oral composition of claim 5, wherein the oral composition is present in an amount up to % by weight. 7. The oral composition of claim 1, wherein the oral composition is a dentifrice containing about 30-75% by weight of a dentally acceptable water-insoluble polishing material. 8. The oral composition is a mouthwash or liquid dentifrice, and the oral composition comprises at least one orally acceptable vehicle.
2. The oral composition of claim 1, wherein the oral composition is an aqueous vehicle containing a surfactant, a fragrance oil, or a non-toxic alcohol. 9. An oral composition according to any of claims 1 to 8, wherein the surfactant is present in an amount of about 05-5% by weight. 10. An oral composition according to any of claims 1 to 9, wherein the aromatic oil is present in an amount of about 01-5% by weight. 11. The oral composition of claim 8, wherein the composition is a mouthwash, the aqueous vehicle contains ethanol, and the water-to-ethanol weight ratio is from about 1:1 to about 20:1. thing. 12. The oral composition contains mannose, glucose, potassium glucuronate, and acetyl moieties in approximately 2:1:1:
Contains about 0.3 to 2.0% by weight of a polysaccharide with a high molecular weight of 1,000,000 or more in a ratio of 1,000,000 or more as a sedimentation prevention and thickening agent, and contains about 10 to 20% by weight of a polished material. The oral composition according to claim 8, which is a liquid dentifrice containing. 13. The oral composition according to any one of claims 1 to 8, wherein the antibacterial agent is selected from the group consisting of halogenated diphenyl ethers, halogenated salicylanilides, benzoic acid esters, halogenated carboanilides, and phenolic compounds. 14. The antibacterial agent is a halogenated diphenyl ether.
The oral composition according to claim 13. 15, the halogenated diphenyl ether is 2,4,4-trichloro-2'-hydroxyphenyl ether,
The oral composition according to claim 14. 16. the solubilizer is present in an amount of about 0.5-50% by weight;
and propylene glycol, dipropylene glycol,
Claims 1 and 3 selected from the group consisting of hexylene glycol, methyl cellosolve, ethyl cellosolve, vegetable oils and waxes containing at least 12 carbon atoms, amyl acetate, ethyl acetate, glyceryl tristearate, and benzyl benzoate. 6. The toothpaste-type oral composition according to any one of 6. 17. The solubilizing agent is propylene glycol, and the solubilizing agent is about 0.
17. The dentifrice-type oral composition of claim 16, wherein the dentifrice-type oral composition is present in an amount of 5% by weight. 18. Polishing materials exist, including sodium metaphosphate, potassium metaphosphate, tricalcium phosphate, dicalcium phosphate dihydrate, anhydrous dicalcium phosphate, calcium pyrophosphate, magnesium orthophosphate, trimagnesium phosphate, and carbonic acid. 17. The oral composition of any of claims 1 or 16, wherein the oral composition is selected from the group consisting of calcium, aluminum silicate, hydrated alumina, silica, bentonite, and mixtures thereof, and wherein the oral composition is a dentifrice. thing. 19. The oral composition according to claim 18, wherein the polishing material is dicalcium phosphate dihydrate or hydrated alumina. 20, antibacterial enhancer is about 100 to about 1,000,000
The oral composition according to any one of claims 1 to 8, having an average molecular weight of. 21. The oral composition of claim 20, wherein the antimicrobial enhancer comprises at least one delivery-enhancing group and at least one organic retention-enhancing group. 22. The oral composition of claim 21, wherein the delivery-enhancing group is oxygen. 23. The oral composition of claim 22, wherein the delivery-enhancing group is selected from the group consisting of carboxylic, phosphonic, phosphinic and sulfonic acids and salts thereof, and mixtures thereof. 24, the organic retention enhancing group has the formula O(X)_n-R (wherein,
X is O, N, S, SO, SO_2, P, PO or Si
and R is hydrophobic alkyl, alkylene, acyl,
Aryl, alkaryl, aralkyl, heterocyclic residues,
or an inert substituted derivative thereof, where n is 1 or zero. 25. Claim 20, wherein the antimicrobial enhancer is an anionic polymer comprising a plurality of delivery-enhancing groups and retention-enhancing groups.
25. The oral composition according to any one of 24 to 24. 26. Claim 25, wherein the anionic polymer consists of a chain comprising repeating units each containing at least one carbon atom.
Oral composition according to. 27. The oral composition of claim 26, wherein each unit comprises at least one delivery-enhancing group attached to the same, vicinal, or other atom in the chain. 28. The oral composition according to claim 23, wherein the delivery-enhancing group is a carboxylic acid group or a salt thereof. 29. The oral composition of claim 28, wherein the antimicrobial enhancer is a copolymer of maleic acid or acid anhydride and other inert ethylenically unsaturated polymerizable monomer. 30. The oral composition of claim 29, wherein the other monomer of the copolymer is methyl vinyl ether in a molar ratio of 4:1 to 1:4 with maleic acid or acid anhydride. 31, copolymer is about 30,000 to 1,000,000
31. The oral composition of claim 30, having a molecular weight of 0 and present in an amount of about 0.1-2% by weight. 32. The composition of claim 31, wherein the copolymer has an average molecular weight of about 70,000. 33. The composition according to claim 23, wherein the delivery-enhancing group is phosphonic acid or a salt thereof. 34. Antibacterial enhancer is poly(β-styrenephosphonic acid)
or a poly(α-styrene phosphonic acid) polymer, or a copolymer of any styrene phosphonic acid and other ethylenically unsaturated monomers. 35. A method for inhibiting dental plaque, which comprises applying the composition according to any one of claims 1 to 34 in an amount that exhibits a plaque inhibiting effect on the surface of the oral cavity. 36, an orally acceptable vehicle, an anti-plaque effective amount of a substantially water-insoluble, non-cationic antimicrobial agent, and an average molecular weight of from about 1,000 to about 1,000,000, and at least one an antimicrobial enhancer containing a delivery-enhancing functional group and at least one organic retention-enhancing group, wherein the enhancer containing those groups has a molecular weight of about
An oral composition that is free or substantially free of water-soluble alkali metal or ammonium salts of synthetic anionic linear polymeric polycarboxylic acids of from 0 to about 1,000,000. 37. The oral composition of claim 36, wherein the antimicrobial agent is present in an amount of about 0.25-0.5% by weight. 38. The oral composition of claim 36, wherein the antimicrobial agent is present in an amount of about 0.25 to about 0.35% by weight. 39. The oral composition according to claim 37, wherein the oral composition contains a siliceous polishing material. 40. The oral composition according to claim 38, wherein the oral composition contains a siliceous polishing material.